<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Mantle cell lymphoma and can you explain it in depth? [/INST] Mantle cell lymphoma (MCL) is a type of non-Hodgkins lymphoma (NHL), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the United States with mantle cell lymphoma.  It is named for the mantle zone of the lymph nodes.
MCL is a subtype of B-cell lymphoma, due to CD5 positive antigen-naive pregerminal center B-cell within the mantle zone that surrounds normal germinal center follicles. MCL cells generally over-express cyclin D1 due to the t(11:14) translocation, a chromosomal translocation in the DNA.

Signs and symptoms
At diagnosis, patients typically are in their 60s and present to their physician with advanced disease. About half have B symptoms such as fever, night sweats, or unexplained weight loss (over 10% of body weight). Enlarged lymph nodes (for example, a "bump" on the neck, armpits or groin) or enlargement of the spleen are usually present. Bone marrow, liver and gastrointestinal tract involvement occurs relatively early in the course of the disease. Mantle cell lymphoma has been reported in rare cases to be associated with severe allergic reactions to mosquito bites. These reactions involve extensive allergic reactions to mosquito bites which range from greatly enlarged bite sites that may be painful and involve necrosis to systemic symptoms (e.g. fever, swollen lymph nodes, abdominal pain, and diarrhea), or, in extremely rare cases, to life-threatening anaphylaxis. In several of these cases, the mosquito bite allergy (MBA) reaction occurred prior to the diagnosis of MCL suggesting that MBA can be a manifestation of early-developing mantle cell lymphoma.

Pathogenesis
MCL, like most cancers, results from the acquisition of a combination of (non-inherited) genetic mutations in somatic cells. This leads to a clonal expansion of malignant B lymphocytes. The factors that initiate the genetic alterations are typically not identifiable, and usually occur in people with no particular risk factors for lymphoma development. Because it is an acquired genetic disorder, MCL is neither communicable nor inheritable.A defining characteristic of MCL is mutation and overexpression of cyclin D1, a cell cycle gene, that contributes to the abnormal proliferation of the malignant cells. MCL cells may also be resistant to drug-induced apoptosis, making them harder to cure with chemotherapy or radiation. Cells affected by MCL proliferate in a nodular or diffuse pattern with two main cytologic variants, typical or blastic. Typical cases are small to intermediate-sized cells with irregular nuclei. Blastic (aka blastoid) variants have intermediate to large-sized cells with finely dispersed chromatin, and are more aggressive in nature. The tumor cells accumulate in the lymphoid system, including lymph nodes and the spleen, with non-useful cells eventually rendering the system dysfunctional. MCL may also replace normal cells in the bone marrow, which impairs normal blood cell production.

Diagnosis
Diagnosis generally requires stained slides of a surgically removed part of a lymph node. Other methods are also commonly used, including cytogenetics and fluorescence in situ hybridization (FISH). Polymerase chain reaction (PCR) and CER3 clonotypic primers are additional methods, but are less often used.The immunophenotype profile consists of CD5+ (in about 80% of cases), CD10-/+, and it is usually CD5+ and CD10-. CD20+, CD23-/+ (though plus in rare cases). Generally, cyclin D1 is expressed. Cyclin D1-negative mantle cell lymphoma can be diagnosed by detecting the SOX11 marker. The workup for mantle cell lymphoma is similar to the workup for many indolent lymphomas and certain aggressive lymphomas.
Mantle cell lymphoma is a systemic disease with frequent involvement of the bone marrow and gastrointestinal tract (generally showing polyposis in the lining). There is also a not-uncommon leukemic phase, marked by its presence in the blood. For this reason, both the peripheral blood and bone marrow are evaluated for the presence of malignant cells. Chest, abdominal, and pelvic CT scans are routinely performed.Since mantle cell lymphoma may present a lymphomatous polyposis coli and colon involvement is common, colonoscopy is considered a routine part of the evaluation. Upper endoscopy and neck CT scan may be helpful in selected cases. In some patients with the blastic variant, lumbar puncture is done to evaluate the spinal fluid for involvement.CT scanPET scan

Treatments
There are no proven standards of treatment for MCL, and there is no consensus among specialists on how to treat it optimally. Many regimens are available and often get good response rates, but patients almost always get disease progression after chemotherapy. Each relapse is typically more difficult to treat, and relapse is generally faster. Regimens are available that treat relapses, and new approaches are under test. Because of the aforementioned factors, many MCL patients enroll in clinical trials to get the latest treatments.There are four classes of treatments in general use: chemotherapy, immunotherapy, radioimmunotherapy and biologic agents. The phases of treatment are generally: frontline, following diagnosis, consolidation, after frontline response (to prolong remissions), and relapse. Relapse is usually experienced multiple times.

Chemotherapy
Chemotherapy is widely used as frontline treatment, and often is not repeated in relapse due to side effects. Alternate chemotherapy is sometimes used at first relapse. For frontline treatment, CHOP with rituximab is the most common chemotherapy, and often given as outpatient by IV. A stronger chemotherapy with greater side effects (mostly hematologic) is HyperCVAD, often given in the hospital setting, with rituximab and generally to fitter patients (some of which are over 65). HyperCVAD is becoming popular and showing promising results, especially with rituximab. It can be used on some elderly (over 65) patients, but seems only beneficial when the baseline Beta-2-MG blood test was normal. It is showing better complete remissions (CR) and progression-free survival (PFS) than CHOP regimens. A less intensive option is bendamustine with rituximab.Second line treatment may include fludarabine, combined with cyclophosphamide and/or mitoxantrone, usually with rituximab. Cladribine and clofarabine are two other medications being investigated in MCL. A relatively new regimen that uses old medications is PEP-C, which includes relatively small, daily doses of prednisone, etoposide, procarbazine, and cyclophosphamide, taken orally, has proven effective for relapsed patients. According to Dr. John Leonard, PEP-C may have anti-angiogenetic properties, something that he and his colleagues are testing through an ongoing drug trial.Another approach involves using very high doses of chemotherapy, sometimes combined with total body irradiation (TBI), in an attempt to destroy all evidence of the disease. The downside to this is the destruction of the patients entire immune system as well, requiring rescue by transplantation of a new immune system (hematopoietic stem cell transplantation), using either autologous stem cell transplantation, or those from a matched donor (an allogeneic stem cell transplant). A presentation at the December 2007 American Society of Hematology (ASH) conference by Christian Geisler, chairman of the Nordic Lymphoma Group claimed that according to trial results, mantle cell lymphoma is potentially curable with very intensive chemo-immunotherapy followed by a stem cell transplant, when treated upon first presentation of the disease.These results seem to be confirmed by a large trial of the European Mantle Cell Lymphoma Network indicating that induction regimens containing monoclonal antibodies and high dose ARA-C (Cytarabine) followed by ASCT should become the new standard of care of MCL patients up to approximately 65 years.A study released in April 2013 showed that patients with previously untreated indolent lymphoma, bendamustine plus rituximab can be considered as a preferred first-line treatment approach to R-CHOP because of increased progression-free survival and fewer toxic effects.

Immunotherapy
Immune-based therapy is dominated by the use of the rituximab monoclonal antibody, sold under the trade name Rituxan (or as Mabthera in Europe and Australia). Rituximab may have good activity against MCL as a single agent, but it is typically given in combination with chemotherapies, which prolongs response duration. There are newer variations on monoclonal antibodies combined with radioactive molecules known as radioimmunotherapy (RIT). These include Zevalin and Bexxar. Rituximab has also been used in small numbers of patients in combination with thalidomide with some effect.  In contrast to these antibody-based passive immunotherapies, the field of active immunotherapy tries to activate a patients immune system to specifically eliminate their own tumor cells.  Examples of active immunotherapy include cancer vaccines, adoptive cell transfer, and immunotransplant, which combines vaccination and autologous stem cell transplant.  Though no active immunotherapies are currently a standard of care, numerous clinical trials are ongoing.

Targeted therapy
Two Bruton tyrosine kinase inhibitors (BTKi), one In November 2013, ibrutinib (trade name Imbruvica, Pharmacyclics LLC) and in October 2017, acalabrutinib (trade name Calquence, AstraZeneca Pharmaceuticals LP) were approved in the United States for treating MCL.
Other targeted agents include the proteasome inhibitor bortezomib, mTOR inhibitors such as  temsirolimus, and the P110δ inhibitor GS-1101.In November 2019, zanubrutinib (Brukinsa) was approved in the United States with an indication for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy.

Gene therapy
Brexucabtagene autoleucel (Tecartus) was approved for medical use in the United States in July 2020, with an indication for the treatment of adults with relapsed or refractory mantle cell lymphoma. It was approved for medical use in the European Union in December 2020.Each dose of brexucabtagene autoleucel is a customized treatment created using the recipients own immune system to help fight the lymphoma. The recipients T cells, a type of white blood cell, are collected and genetically modified to include a new gene that facilitates the targeting and killing of the lymphoma cells. These modified T cells are then infused back into the recipient.

Prognosis
Recent clinical advances in mantle cell lymphoma (MCL) have seen standard‐of‐care treatment algorithms transformed. Frontline rituximab combination therapy, high dose cytarabine‐based induction in younger patients and, more recently, Bruton Tyrosine Kinase (BTK) inhibitors in the relapse setting have all demonstrated survival advantage in clinical trials (Wang et al., 2013; Eskelund et al., 2016; Rule et al., 2016). Over the last 15 years these practices have gradually become embedded in clinical practice and real‐world data has observed corresponding improvements in patient survival (Abrahamsson et al., 2014; Leux et al., 2014).The overall 5-year survival rate for MCL is generally 50% (advanced stage MCL) to 70% (for limited-stage MCL).
Prognosis for individuals with MCL is problematic and indexes do not work as well due to patients presenting with advanced stage disease. Staging is used but is not very informative, since the malignant B-cells can travel freely though the lymphatic system and therefore most patients are at stage III or IV at diagnosis. Prognosis is not strongly affected by staging in MCL and the concept of metastasis does not really apply.The Mantle Cell Lymphoma International Prognostic Index (MIPI) was derived from a data set of 455 advanced stage MCL patients treated in series of clinical trials in Germany/Europe. Of the evaluable population, approximately 18% were treated with high-dose therapy and stem cell transplantation in first remission. The MIPI is able to classify patients into three risk groups: low risk (median survival not reached after median 32 months follow-up and 5-year OS rate of 60%), intermediate risk (median survival 51 months) and high risk (median survival 29 months). In addition to the 4 independent prognostic factors included in the model, the cell proliferation index (Ki-67) was also shown to have additional prognostic relevance. When the Ki67 is available, a biologic MIPI can be calculated.MCL is one of the few NHLs that can cross the boundary into the brain, yet it can be treated in that event.There are a number of prognostic indicators that have been studied. There is not universal agreement on their importance or usefulness in prognosis.Ki-67 is an indicator of how fast cells mature and is expressed in a range from about 10% to 90%. The lower the percentage, the lower the speed of maturity, and the more indolent the disease. Katzenberger et al. Blood 2006;107:3407 graphs survival versus time for subsets of patients with varying Ki-67 indices. He shows median survival times of about one year for 61-90% Ki-67 and nearly 4 years for 5-20% Ki-67 index.
MCL cell types can aid in prognosis in a subjective way. Blastic is a larger cell type. Diffuse is spread through the node. Nodular are small groups of collected cells spread through the node. Diffuse and nodular are similar in behavior. Blastic is faster growing and it is harder to get long remissions. Some thought is that given a long time, some non-blastic MCL transforms to blastic. Although survival of most blastic patients is shorter, some data shows that 25% of blastic MCL patients survive to 5 years. That is longer than diffuse type and almost as long as nodular (almost 7 yrs).Beta-2 microglobulin is another risk factor in MCL used primarily for transplant patients. Values less than three have yielded 95% overall survival to six years for auto SCT where over three yields a median of 44 most overall survival for auto SCT (Khouri 03). This is not yet fully validated.Testing for high levels of Lactate dehydrogenase (LDH) in NHL patients is useful because LDH is released when body tissues break down for any reason. While it cannot be used as a sole means of diagnosing NHL, it is a surrogate for tracking tumor burden in those diagnosed by other means. The normal range is approximately 100–190.

Epidemiology
6% of non-Hodgkin lymphoma cases are mantle cell lymphoma. As of 2015, the ratio of males to females affected is about 4:1.

See also
In situ mantle cell lymphoma
List of hematologic conditions

References
Further reading
Cohen JB, Zain JM, Kahl BS (2017). "Current Approaches to Mantle Cell Lymphoma: Diagnosis, Prognosis, and Therapies". Am Soc Clin Oncol Educ Book. 37 (37): 512–25. doi:10.1200/EDBK_175448. PMID 28561694.
Dreyling M, Ferrero S, Hermine O (November 2014). "How to manage mantle cell lymphoma". Leukemia </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Surgery and can you explain it in depth? [/INST] Surgery is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pathological condition such as a disease or injury, to help improve bodily function, appearance, or to repair unwanted ruptured areas.
The act of performing surgery may be called a surgical procedure, operation, or simply "surgery". In this context, the verb "operate" means to perform surgery. The adjective surgical means pertaining to surgery; e.g. surgical instruments or surgical nurse. The person or subject on which the surgery is performed can be a person or an animal. A surgeon is a person who practices surgery and a surgeons assistant is a person who practices surgical assistance. A surgical team is made up of the surgeon, the surgeons assistant, an anaesthetist, a circulating nurse and a surgical technologist. Surgery usually spans from minutes to hours, but it is typically not an ongoing or periodic type of treatment. The term "surgery" can also refer to the place where surgery is performed, or, in British English, simply the office of a physician, dentist, or veterinarian.

Definitions
Surgery is an invasive technique with the fundamental principle of physical intervention on organs/organ systems/tissues for diagnostic or therapeutic reasons.
As a general rule, a procedure is considered surgical when it involves cutting of a persons tissues or closure of a previously sustained wound.  Other procedures that do not necessarily fall under this rubric, such as angioplasty or endoscopy, may be considered surgery if they involve "common" surgical procedure or settings, such as use of a sterile environment, anesthesia, antiseptic conditions, typical surgical instruments, and suturing or stapling.  All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being excised (e.g. laser ablation of the cornea) or to a radiosurgical procedure (e.g. irradiation of a tumor).

Types of surgery
Surgical procedures are commonly categorized by urgency, type of procedure, body system involved, the degree of invasiveness, and special instrumentation.

Based on timing: Elective surgery is done to correct a non-life-threatening condition, and is carried out at the persons request, subject to the surgeons and the surgical facilitys availability. A semi-elective surgery is one that must be done to avoid permanent disability or death, but can be postponed for a short time. Emergency surgery is surgery which must be done without any delay to prevent death or serious disabilities and/or loss of limbs and functions.
Based on purpose: Exploratory surgery is performed to aid or confirm a diagnosis. Therapeutic surgery treats a previously diagnosed condition. Cosmetic surgery is done to subjectively improve the appearance of an otherwise normal structure.

By type of procedure: Amputation involves cutting off a body part, usually a limb or digit; castration is also an example. Resection is the removal of all of an internal organ or body part, or a key part (lung lobe; liver quadrant) of such an organ or body part that has its own name or code designation. A segmental resection can be of a smaller region of an organ such as a hepatic segment or a bronchopulmonary segment. Excision is the cutting out or removal of only part of an organ, tissue, or other body part from the person. Extirpation is the complete excision or surgical destruction of a body part. Replantation involves reattaching a severed body part. Reconstructive surgery involves reconstruction of an injured, mutilated, or deformed part of the body. Transplant surgery is the replacement of an organ or body part by insertion of another from different human (or animal) into the person undergoing surgery. Removing an organ or body part from a live human or animal for use in transplant is also a type of surgery.
By body part: When surgery is performed on one organ system or structure, it may be classed by the organ, organ system or tissue involved. Examples include cardiac surgery (performed on the heart), gastrointestinal surgery (performed within the digestive tract and its accessory organs), and orthopedic surgery (performed on bones or muscles).
By degree of invasiveness of surgical procedures: Minimally-invasive surgery involves smaller outer incisions to insert miniaturized instruments within a body cavity or structure, as in laparoscopic surgery or angioplasty. By contrast, an open surgical procedure such as a laparotomy requires a large incision to access the area of interest.
By equipment used: Laser surgery involves use of a laser for cutting tissue instead of a scalpel or similar surgical instruments. Microsurgery involves the use of an operating microscope for the surgeon to see small structures. Robotic surgery makes use of a surgical robot, such as the Da Vinci or the ZEUS robotic surgical systems, to control the instrumentation under the direction of the surgeon.

Terminology
Excision surgery names often start with a name for the organ to be excised (cut out) and end in -ectomy.
Procedures involving cutting into an organ or tissue end in -otomy.  A surgical procedure cutting through the abdominal wall to gain access to the abdominal cavity is a laparotomy.
Minimally invasive procedures, involving small incisions through which an endoscope is inserted, end in -oscopy.  For example, such surgery in the abdominal cavity is called laparoscopy.
Procedures for formation of a permanent or semi-permanent opening called a stoma in the body end in -ostomy.
Reconstruction, plastic or cosmetic surgery of a body part starts with a name for the body part to be reconstructed and ends in -oplasty.  Rhino is used as a prefix for "nose", therefore a rhinoplasty is reconstructive or cosmetic surgery for the nose.
Repair of damaged or congenital abnormal structure ends in -rraphy.
Reoperation (return to the operating room) refers to a return to the operating theater after an initial surgery is performed to re-address an aspect of patient care best treated surgically. Reasons for reoperation include persistent bleeding after surgery, development of or persistence of infection.

Description of surgical procedure
Location
Inpatient surgery is performed in a hospital, and the person undergoing surgery stays at least one night in the hospital after the surgery. Outpatient surgery occurs in a hospital outpatient department or freestanding ambulatory surgery center, and the person who had surgery is discharged the same working day. Office surgery occurs in a physicians office, and the person is discharged the same working day.At a hospital, modern surgery is often performed in an operating theater using surgical instruments, an operating table, and other equipment. Among United States hospitalizations for non-maternal and non-neonatal conditions in 2012, more than one-fourth of stays and half of hospital costs involved stays that included operating room (OR) procedures. The environment and procedures used in surgery are governed by the principles of aseptic technique: the strict separation of "sterile" (free of microorganisms) things from "unsterile" or "contaminated" things.  All surgical instruments must be sterilized, and an instrument must be replaced or re-sterilized if it becomes contaminated (i.e. handled in an unsterile manner, or allowed to touch an unsterile surface). Operating room staff must wear sterile attire (scrubs, a scrub cap, a sterile surgical gown, sterile latex or non-latex polymer gloves and a surgical mask), and they must scrub hands and arms with an approved disinfectant agent before each procedure.

Preoperative care
Prior to surgery, the person is given a medical examination, receives certain pre-operative tests, and their physical status is rated according to the ASA physical status classification system. If these results are satisfactory, the person requiring surgery signs a consent form and is given a surgical clearance. If the procedure is expected to result in significant blood loss, an autologous blood donation may be made some weeks prior to surgery. If the surgery involves the digestive system, the person requiring surgery may be instructed to perform a bowel prep by drinking a solution of polyethylene glycol the night before the procedure. People preparing for surgery are also instructed to abstain from food or drink (an NPO order after midnight on the night before the procedure), to minimize the effect of stomach contents on pre-operative medications and reduce the risk of aspiration if the person vomits during or after the procedure.
Some medical systems have a practice of routinely performing chest x-rays before surgery. The premise behind this practice is that the physician might discover some unknown medical condition which would complicate the surgery, and that upon discovering this with the chest x-ray, the physician would adapt the surgery practice accordingly. However, medical specialty professional organizations recommend against routine pre-operative chest x-rays for people who have an unremarkable medical history and presented with a physical exam which did not indicate a chest x-ray. Routine x-ray examination is more likely to result in problems like misdiagnosis, overtreatment, or other negative outcomes than it is to result in a benefit to the person. Likewise, other tests including complete blood count, prothrombin time, partial thromboplastin time, basic metabolic panel, and urinalysis should not be done unless the results of these tests can help evaluate surgical risk.

Staging for surgery
The pre-operative holding area is so important in the surgical phase since here is where most of the family members can see who the staff of the surgery will be, also this area is where the nurses in charge to give information to the family members of the patient. In the pre-operative holding area, the person preparing for surgery changes out of his or her street clothes and is asked to confirm the details of his or her surgery. A set of vital signs are recorded, a peripheral IV line is placed, and pre-operative medications (antibiotics, sedatives, etc.) are given. When the person enters the operating room, the skin surface to be operated on, called the operating field, is cleaned and prepared by applying an antiseptic (ideally chlorhexidine gluconate in alcohol, as this is twice as effective as povidone-iodine at reducing the risk of infection). If hair is present at the surgical site, it is clipped off prior to prep application. The person is assisted by an anesthesiologist or resident to make a specific surgical position, then sterile drapes are used to cover the surgical site or at least a wide area surrounding the operating field; the drapes are clipped to a pair of poles near the head of the bed to form an "ether screen", which separates the anesthetist/anesthesiologists working area (unsterile) from the surgical site (sterile).Anesthesia is administered to prevent pain from an incision, tissue manipulation and suturing.  Depending on the kind of operation, anesthesia may be provided locally or as general anesthesia.  Spinal anesthesia may be used when the surgical site is too large or deep for a local block, but general anesthesia may not be desirable.  With local and spinal anesthesia, the surgical site is anesthetized, but the person can remain conscious or minimally sedated.  In contrast, general anesthesia renders the person unconscious and paralyzed during surgery.  The person is intubated and is placed on a mechanical ventilator, and anesthesia is produced by a combination of injected and inhaled agents.
Choice of surgical method and anesthetic technique aims to reduce the risk of complications, shorten the time needed for recovery and minimise the surgical stress response.

Intraoperative phase
The intraoperative phase begins when the surgery subject is received in the surgical area (such as the operating theater or surgical department), and lasts until the subject is transferred to a recovery area (such as a post-anesthesia care unit).An incision is made to access the surgical site.  Blood vessels may be clamped or cauterized to prevent bleeding, and retractors may be used to expose the site or keep the incision open.  The approach to the surgical site may involve several layers of incision and dissection, as in abdominal surgery, where the incision must traverse skin, subcutaneous tissue, three layers of muscle and then the peritoneum.  In certain cases, bone may be cut to further access the interior of the body; for example, cutting the skull for brain surgery or cutting the sternum for thoracic (chest) surgery to open up the rib cage. Whilst in surgery aseptic technique is used to prevent infection or further spreading of the disease. The surgeons and assistants hands, wrists and forearms are washed thoroughly for at least 4 minutes to prevent germs getting into the operative field, then sterile gloves are placed onto their hands. An antiseptic solution is applied to the area of the persons body that will be operated on. Sterile drapes are placed around the operative site. Surgical masks are worn by the surgical team to avoid germs on droplets of liquid from their mouths and noses from contaminating the operative site.
Work to correct the problem in body then proceeds.  This work may involve:

excision – cutting out an organ, tumor, or other tissue.
resection – partial removal of an organ or other bodily structure.
reconnection of organs, tissues, etc., particularly if severed.  Resection of organs such as intestines involves reconnection.  Internal suturing or stapling may be used.  Surgical connection between blood vessels or other tubular or hollow structures such as loops of intestine is called anastomosis.
reduction – the movement or realignment of a body part to its normal position.  e.g. Reduction of a broken nose involves the physical manipulation of the bone or cartilage from their displaced state back to their original position to restore normal airflow and aesthetics.
ligation – tying off blood vessels, ducts, or "tubes".
grafts – may be severed pieces of tissue cut from the same (or different) body or flaps of tissue still partly connected to the body but resewn for rearranging or restructuring of the area of the body in question.  Although grafting is often used in cosmetic surgery, it is also used in other surgery.  Grafts may be taken from one area of the persons body and inserted to another area of the body.  An example is bypass surgery, where clogged blood vessels are bypassed with a graft from another part of the body.  Alternatively, grafts may be from other persons, cadavers, or animals.
insertion of prosthetic parts when needed.  Pins or screws to set and hold bones may be used.  Sections of bone may be replaced with prosthetic rods or other parts.  Sometimes a plate is inserted to replace a damaged area of skull.  Artificial hip replacement has become more common.  Heart pacemakers or valves may be inserted.  Many other types of prostheses are used.
creation of a stoma, a permanent or semi-permanent opening in the body
in transplant surgery, the donor organ (taken out of the donors body) is inserted into the recipients body and reconnected to the recipient in all necessary ways (blood vessels, ducts, etc.).
arthrodesis – surgical connection of adjacent bones so the bones can grow together into one. Spinal fusion is an example of adjacent vertebrae connected allowing them to grow together into one piece.
modifying the digestive tract in bariatric surgery for weight loss.
repair of a fistula, hernia, or prolapse.
repair according to the ICD-10-PCS, in the Medical and Surgical Section 0, root operation Q, means restoring, to the extent possible, a body part to its normal anatomic structure and function. This definition, repair, is used only when the method used to accomplish the repair is not one of the other root operations. Examples would be colostomy takedown, herniorrhaphy of a hernia, and the surgical suture of a laceration.
other procedures, including:clearing clogged ducts, blood or other vessels
removal of calculi (stones)
draining of accumulated fluids
debridement – removal of dead, damaged, or diseased tissueBlood or blood expanders may be administered to compensate for blood lost during surgery.  Once the procedure is complete, sutures or staples are used to close the incision.  Once the incision is closed, the anesthetic agents are stopped or reversed, and the person is taken off ventilation and extubated (if general anesthesia was administered).

Postoperative care
After completion of surgery, the person is transferred to the post anesthesia care unit and closely monitored.  When the person is judged to have recovered from the anesthesia, he/she is either transferred to a surgical ward elsewhere in the hospital or discharged home.  During the post-operative period, the persons general function is assessed, the outcome of the procedure is assessed, and the surgical site is checked for signs of infection. There are several risk factors associated with postoperative complications, such as immune deficiency and obesity. Obesity has long been considered a risk factor for adverse post-surgical outcomes. It has been linked to many disorders such as obesity hypoventilation syndrome, atelectasis and pulmonary embolism, adverse cardiovascular effects, and wound healing complications. If removable skin closures are used, they are removed after 7 to 10 days post-operatively, or after healing of the incision is well under way.
It is not uncommon for surgical drains to be required to remove blood or fluid from the surgical wound during recovery. Mostly these drains stay in until the volume tapers off, then they are removed.  These drains can become clogged, leading to abscess.
Postoperative therapy may include adjuvant treatment such as chemotherapy, radiation therapy, or administration of medication such as anti-rejection medication for transplants. For postoperative nausea and vomiting (PONV), solutions like saline, water, controlled breathing placebo and aromatherapy can be used in addition to medication. Other follow-up studies or rehabilitation may be prescribed during and after the recovery period. A recent post-operative care philosophy has been early ambulation. Ambulation is getting the patient moving around. This can be as simple as sitting up or even walking around. The goal is to get the patient moving as early as possible. It has been found to shorten the patients length of stay. Length of stay is the amount of time a patient spends in the hospital after surgery before they are discharged. In a recent study done with lumbar decompressions, the patients length of stay was decreased by 1–3 days.
The use of topical antibiotics on surgical wounds to reduce infection rates has been questioned. Antibiotic ointments are likely to irritate the skin, slow healing, and could increase risk of developing contact dermatitis and antibiotic resistance. It has also been suggested that topical antibiotics should only be used when a person shows signs of infection and not as a preventative. A systematic review published by Cochrane (organisation) in 2016, though, concluded that topical antibiotics applied over certain types of surgical wounds reduce the risk of surgical site infections, when compared to no treatment or use of antiseptics. The review also did not find conclusive evidence to suggest that topical antibiotics increased the risk of local skin reactions or antibiotic resistance.
Through a retrospective analysis of national administrative data, the association between mortality and day of elective surgical procedure suggests a higher risk in procedures carried out later in the working week and on weekends. The odds of death were 44% and 82% higher respectively when comparing procedures on a Friday to a weekend procedure. This "weekday effect" has been postulated to be from several factors including poorer availability of services on a weekend, and also, decrease number and level of experience over a weekend.Postoperative pain affects an estimated 80% of people who underwent surgery. While pain is expected after surgery, there is growing evidence that pain may be inadequately treated in many people in the acute period immediately after surgery. It has been reported that incidence of inadequately controlled pain after surgery ranged from 25.1% to 78.4% across all surgical disciplines. There is insufficient evidence to determine if giving opioid pain medication pre-emptively (before surgery) reduces postoperative pain the amount of medication needed after surgery.Postoperative recovery has been defined as an energy‐requiring process to decrease physical symptoms, reach a level of emotional well‐being, regain functions, and re‐establish activities. Moreover, it has been identified that patients who have undergone surgery are often not fully recovered on discharge.

Epidemiology
United States
In 2011, of the 38.6 million hospital stays in U.S. hospitals, 29% included at least one operating room procedure. These stays accounted for 48% of the total $387 billion in hospital costs.The overall number of procedures remained stable from 2001 to 2011. In 2011, over 15 million operating room procedures were performed in U.S. hospitals.Data from 2003 to 2011 showed that U.S. hospital costs were highest for the surgical service line; the surgical service line costs were $17,600 in 2003 and projected to be $22,500 in 2013. For hospital stays in 2012 in the United States, private insurance had the highest percentage of surgical expenditure. in 2012, mean hospital costs in the United States were highest for surgical stays.

Special populations
Elderly people
Older adults have widely varying physical health.  Frail elderly people are at significant risk of post-surgical complications and the need for extended care.  Assessment of older people before elective surgery can accurately predict the persons recovery trajectories. One frailty scale uses five items:  unintentional weight loss, muscle weakness, exhaustion, low physical activity, and slowed walking speed.  A healthy person scores 0; a very frail person scores 5.  Compared to non-frail elderly people, people with intermediate frailty scores (2 or 3) are twice as likely to have post-surgical complications, spend 50% more time in the hospital, and are three times as likely to be discharged to a skilled nursing facility instead of to their own homes. People who are frail and elderly (score of 4 or 5) have even worse outcomes, with the risk of being discharged to a nursing home rising to twenty times the rate for non-frail elderly people.

Children
Surgery on children requires considerations that are not common in adult surgery. Children and adolescents are still developing physically and mentally making it difficult for them to make informed decisions and give consent for surgical treatments. Bariatric surgery in youth is among the controversial topics related to surgery in children.

Vulnerable populations
Doctors perform surgery with the consent of the person undergoing surgery. Some people are able to give better informed consent than others. Populations such as incarcerated persons, people living with dementia, the mentally incompetent, persons subject to coercion, and other people who are not able to make decisions with the same authority as others, have special needs when making decisions about their personal healthcare, including surgery.

Global surgery
Global surgery has been defined as the multidisciplinary enterprise of providing improved and equitable surgical care to the worlds population, with its core belief as the issues of need, access and quality. Halfdan T. Mahler, the 3rd Director-General of the World Health Organization (WHO), first brought attention to the disparities in surgery and surgical care in 1980 when he stated in his address to the World Congress of the International College of Surgeons, "the vast majority of the worlds population has no access whatsoever to skilled surgical care and little is being done to find a solution." As such, surgical care globally has been described as the neglected stepchild of global health, a term coined by Dr. Paul Farmer to highlight the urgent need for further work in this area. Furthermore, Jim Young Kim, the former President of the World Bank, proclaimed in 2014 that "surgery is an indivisible, indispensable part of health care and of progress towards universal health coverage."In 2015, the Lancet Commission on Global Surgery (LCoGS) published the landmark report titled "Global Surgery 2030: evidence and solutions for achieving health, welfare, and economic development," describing the large, pre-existing burden of surgical diseases in low- and middle-income countries (LMICs) and future directions for increasing universal access to safe surgery by the year 2030. The Commission highlighted that about 5 billion people lack access to safe and affordable surgical and anesthesia care and 143 million additional procedures were needed every year to prevent further morbidity and mortality from treatable surgical conditions as well as a $12.3 trillion loss in economic productivity by the year 2030. This was especially true in the poorest countries, which account for over one-third of the population but only 3.5% of all surgeries that occur worldwide. It emphasized the need to significantly improve the capacity for Bellwether procedures – laparotomy, caesarean section, open fracture care – which are considered a minimum level of care that first-level hospitals should be able to provide in order to capture the most basic emergency surgical care. In terms of the financial impact on the patients, the lack of adequate surgical and anesthesia care has resulted in 33 million individuals every year facing catastrophic health expenditure – the out-of-pocket healthcare cost exceeding 40% of a given households income.In alignment with the LCoGS call for action, the World Health Assembly adopted the resolution WHA68.15 in 2015 that stated, "Strengthening emergency and essential surgical care and anesthesia as a component of universal health coverage." This not only mandated the WHO to prioritize strengthening the surgical and anesthesia care globally, but also led to governments of the member states recognizing the urgent need for increasing capacity in surgery and anesthesia. Additionally, the third edition of Disease Control Priorities (DCP3), published in 2015 by the World Bank, declared surgery as essential and featured an entire volume dedicated to building surgical capacity.Data from WHO and the World Bank indicate that scaling up infrastructure to enable access to surgical care in regions where it is currently limited or is non-existent is a low-cost measure relative to the significant morbidity and mortality caused by lack of surgical treatment. In fact, a systematic review found that the cost-effectiveness ratio – dollars spent per DALYs averted – for surgical interventions is on par or exceeds those of major public health interventions such as oral rehydration therapy, breastfeeding promotion, and even HIV/AIDS antiretroviral therapy. This finding challenged the common misconception that surgical care is financially prohibitive endeavor not worth pursuing in LMICs.
A key policy framework that arose from this renewed global commitment towards surgical care worldwide is the National Surgical Obstetric and Anesthesia Plan (NSOAP). NSOAP focuses on policy-to-action capacity building for surgical care with tangible steps as follows: (1) analysis of baseline indicators, (2) partnership with local champions, (3) broad stakeholder engagement, (4) consensus building and synthesis of ideas, (5) language refinement, (6) costing, (7) dissemination, and (8) implementation. This approach has been widely adopted and has served as guiding principles between international collaborators and local institutions and governments. Successful implementations have allowed for sustainability in terms of longterm monitoring, quality improvement, and continued political and financial support.

Human rights
Access to surgical care is increasingly recognized as an integral aspect of healthcare, and therefore is evolving into a normative derivation of human right to health. The ICESCR Article 12.1 and 12.2 define the human right to health as "the right of everyone to the enjoyment of the highest attainable standard of physical and mental health" In the August 2000, the UN Committee on Economic, Social and Cultural Rights (CESCR) interpreted this to mean "right to the enjoyment of a variety of facilities, goods, services, and conditions necessary for the realization of the highest attainable health". Surgical care can be thereby viewed as a positive right – an entitlement to protective healthcare.Woven through the International Human and Health Rights literature is the right to be free from surgical disease. The 1966 ICESCR Article 12.2a described the need for "provision for the reduction of the stillbirth-rate and of infant mortality and for the healthy development of the child" which was subsequently interpreted to mean "requiring measures to improve… emergency obstetric services". Article 12.2d of the ICESCR stipulates the need for "the creation of conditions which would assure to all medical service and medical attention in the event of sickness", and is interpreted in the 2000 comment to include timely access to "basic preventative, curative services… for appropriate treatment of injury and disability.". Obstetric care shares close ties with reproductive rights, which includes access to reproductive health.Surgeons and public health advocates, such as Kelly McQueen, have described surgery as "Integral to the right to health". This is reflected in the establishment of the WHO Global Initiative for Emergency and Essential Surgical Care in 2005, the 2013 formation of the Lancet Commission for Global Surgery, the 2015 World Bank Publication of Volume 1 of its Disease Control Priorities Project "Essential Surgery", and the 2015 World Health Assembly 68.15 passing of the Resolution for Strengthening Emergency and Essential Surgical Care and Anesthesia as a Component of Universal Health Coverage. The Lancet Commission for Global Surgery outlined the need for access to "available, affordable, timely and safe" surgical and anesthesia care; dimensions paralleled in ICESCR General Comment No. 14, which similarly outlines need for available, accessible, affordable and timely healthcare.

History
Trepanation
Surgical treatments date back to the prehistoric era. The oldest for which there is evidence is trepanation, in which a hole is drilled or scraped into the skull, thus exposing the dura mater in order to treat health problems related to intracranial pressure and other diseases.

Ancient Egypt
Prehistoric surgical techniques are seen in Ancient Egypt, where a mandible dated to approximately 2650 BC shows two perforations just below the root of the first molar, indicating the draining of an abscessed tooth. Surgical texts from ancient Egypt date back about 3500 years ago. Surgical operations were performed by priests, specialized in medical treatments similar to today, and used sutures to close wounds. Infections were treated with honey.

India
Remains from the early Harappan periods of the Indus Valley civilization (c. 3300 BC) show evidence of teeth having been drilled dating back 9,000 years. Sushruta Samhita is one of the oldest known surgical texts and its period is usually placed around 1200–600 BC. It describes in detail the examination, diagnosis, treatment, and prognosis of numerous ailments, as well as procedures for various forms of cosmetic surgery, plastic surgery and rhinoplasty.

Ancient and Medieval Greece
In ancient Greece, temples dedicated to the healer-god Asclepius, known as Asclepieia (Greek: Ασκληπιεία, sing. Asclepieion Ασκληπιείον), functioned as centers of medical advice, prognosis, and healing. In the Asclepieion of Epidaurus, some of the surgical cures listed, such as the opening of an abdominal abscess or the removal of traumatic foreign material, are realistic enough to have taken place. The Greek Galen was one of the greatest surgeons of the ancient world and performed many audacious operations – including brain and eye surgery – that were not tried again for almost two millennia.
Researchers from the Adelphi University discovered in the Paliokastro on Thasos ten skeletal remains, four women and six men, who were buried between the fourth and seventh centuries A.D. Their bones illuminated their physical activities, traumas, and even a complex form of brain surgery. According to the researchers: "The very serious trauma cases sustained by both males and females had been treated surgically or orthopedically by a very experienced physician/surgeon with great training in trauma care. We believe it to have been a military physician". The researchers were impressed by the complexity of the brain surgical operation.In 1991 at the Polystylon fort in Greece, researchers discovered the head of a Byzantine warrior of the 14th century. Analysis of the lower jaw revealed that a surgery has been performed, when the warrior was alive, to the jaw which had been badly fractured and it tied back together until it healed.

Islamic world
During the Islamic Golden Age, largely based upon Paul of Aeginas Pragmateia, the writings of Abulcasis (Abu al-Qasim Khalaf ibn al-Abbas Al-Zahrawi), an Andalusian-Arab physician and scientist who practiced in the Zahra suburb of Córdoba, were influential. Al-Zahrawi specialized in curing disease by cauterization. He invented several surgical instruments for purposes such as inspection of the interior of the urethra and for removing foreign bodies from the throat, the ear, and other body organs. He was also the first to illustrate the various cannulae and to treat warts with an iron tube and caustic metal as a boring instrument. He describes what is thought to be the first attempt at reduction mammaplasty for the management of gynaecomastia and the first mastectomy to treat breast cancer. He is credited with the performance of the first thyroidectomy. Al-Zahrawi pioneered techniques of neurosurgery and neurological diagnosis, treating head injuries, skull fractures, spinal injuries, hydrocephalus, subdural effusions and headache. The first clinical description of an operative procedure for hydrocephalus was given by Al-Zahrawi, who clearly describes the evacuation of superficial intracranial fluid in hydrocephalic children.

Early modern Europe
In Europe, the demand grew for surgeons to formally study for many years before practicing; universities such as Montpellier, Padua and Bologna were particularly renowned. In the 12th century, Rogerius Salernitanus composed his Chirurgia, laying the foundation for modern Western surgical manuals. Barber-surgeons generally had a bad reputation that was not to improve until the development of academic surgery as a specialty of medicine, rather than an accessory field. Basic surgical principles for asepsis etc., are known as Halsteads principles.
There were some important advances to the art of surgery during this period. The professor of anatomy at the University of Padua, Andreas Vesalius, was a pivotal figure in the Renaissance transition from classical medicine and anatomy based on the works of Galen, to an empirical approach of hands-on dissection. In his anatomic treaties De humani corporis fabrica, he exposed the many anatomical errors in Galen and advocated that all surgeons should train by engaging in practical dissections themselves.
The second figure of importance in this era was Ambroise Paré (sometimes spelled "Ambrose"), a French army surgeon from the 1530s until his death in 1590. The practice for cauterizing gunshot wounds on the battlefield had been to use boiling oil; an extremely dangerous and painful procedure. Paré began to employ a less irritating emollient, made of egg yolk, rose oil and turpentine. He also described more efficient techniques for the effective ligation of the blood vessels during an amputation.

Modern surgery
The discipline of surgery was put on a sound, scientific footing during the Age of Enlightenment in Europe. An important figure in this regard was the Scottish surgical scientist, John Hunter, generally regarded as the father of modern scientific surgery. He brought an empirical and experimental approach to the science and was renowned around Europe for the quality of his research and his written works. Hunter reconstructed surgical knowledge from scratch; refusing to rely on the testimonies of others, he conducted his own surgical experiments to determine the truth of the matter. To aid comparative analysis, he built up a collection of over 13,000 specimens of separate organ systems, from the simplest plants and animals to humans.
He greatly advanced knowledge of venereal disease and introduced many new techniques of surgery, including new methods for repairing damage to the Achilles tendon and a more effective method for applying ligature of the arteries in case of an aneurysm. He was also one of the first to understand the importance of pathology, the danger of the spread of infection and how the problem of inflammation of the wound, bone lesions and even tuberculosis often undid any benefit that was gained from the intervention. He consequently adopted the position that all surgical procedures should be used only as a last resort.Other important 18th- and early 19th-century surgeons included Percival Pott (1713–1788) who described tuberculosis on the spine and first demonstrated that a cancer may be caused by an environmental carcinogen (he noticed a connection between chimney sweeps exposure to soot and their high incidence of scrotal cancer). Astley Paston Cooper (1768–1841) first performed a successful ligation of the abdominal aorta, and James Syme (1799–1870) pioneered the Symes Amputation for the ankle joint and successfully carried out the first hip disarticulation.
Modern pain control through anesthesia was discovered in the mid-19th century. Before the advent of anesthesia, surgery was a traumatically painful procedure and surgeons were encouraged to be as swift as possible to minimize patient suffering.  This also meant that operations were largely restricted to amputations and external growth removals. Beginning in the 1840s, surgery began to change dramatically in character with the discovery of effective and practical anaesthetic chemicals such as ether, first used by the American surgeon Crawford Long, and chloroform, discovered by Scottish obstetrician James Young Simpson and later pioneered by John Snow, physician to Queen Victoria. In addition to relieving patient suffering, anaesthesia allowed more intricate operations in the internal regions of the human body.  In addition, the discovery of muscle relaxants such as curare allowed for safer applications.

Infection and antisepsis
Unfortunately, the introduction of anesthetics encouraged more surgery, which inadvertently caused more dangerous patient post-operative infections.  The concept of infection was unknown until relatively modern times. The first progress in combating infection was made in 1847 by the Hungarian doctor Ignaz Semmelweis who noticed that medical students fresh from the dissecting room were causing excess maternal death compared to midwives. Semmelweis, despite ridicule and opposition, introduced compulsory handwashing for everyone entering the maternal wards and was rewarded with a plunge in maternal and fetal deaths; however, the Royal Society dismissed his advice.

Until the pioneering work of British surgeon Joseph Lister in the 1860s, most medical men believed that chemical damage from exposures to bad air (see "miasma") was responsible for infections in wounds, and facilities for washing hands or a patients wounds were not available. Lister became aware of the work of French chemist Louis Pasteur, who showed that rotting and fermentation could occur under anaerobic conditions if micro-organisms were present.  Pasteur suggested three methods to eliminate the micro-organisms responsible for gangrene: filtration, exposure to heat, or exposure to chemical solutions. Lister confirmed Pasteurs conclusions with his own experiments and decided to use his findings to develop antiseptic techniques for wounds.  As the first two methods suggested by Pasteur were inappropriate for the treatment of human tissue, Lister experimented with the third, spraying carbolic acid on his instruments. He found that this remarkably reduced the incidence of gangrene and he published his results in The Lancet. Later, on 9 August 1867, he read a paper before the British Medical Association in Dublin, on the Antiseptic Principle of the Practice of Surgery, which was reprinted in the British Medical Journal. His work was groundbreaking and laid the foundations for a rapid advance in infection control that saw modern antiseptic operating theatres widely used within 50 years.
Lister continued to develop improved methods of antisepsis and asepsis when he realised that infection could be better avoided by preventing bacteria from getting into wounds in the first place. This led to the rise of sterile surgery. Lister introduced the Steam Steriliser to sterilize equipment, instituted rigorous hand washing and later implemented the wearing of rubber gloves. These three crucial advances – the adoption of a scientific methodology toward surgical operations, the use of anaesthetic and the introduction of sterilised equipment – laid the groundwork for the modern invasive surgical techniques of today.
The use of X-rays as an important medical diagnostic tool began with their discovery in 1895 by German physicist Wilhelm Röntgen. He noticed that these rays could penetrate the skin, allowing the skeletal structure to be captured on a specially treated photographic plate.

Surgical specialties
Learned societies
See also
List of Surgery-related fields
Notes
References
Further reading
Bartolo, M., Bargellesi, S., Castioni, C. A., Intiso, D., Fontana, A., Copetti, M., Scarponi, F.,  Bonaiuti, D., & Intensive Care and Neurorehabilitation Italian Study Group (2017). Mobilization in early rehabilitation in intensive care unit patients with severe acquired brain injury: An observational study. Journal of rehabilitation medicine, 49(9), 715–722. https://doi.org/10.2340/16501977-2269
Ni, C.-yan, Wang, Z.-hong, Huang, Z.-ping, Zhou, H., Fu, L.-juan, Cai, H., Huang,   X.-xuan, Yang, Y., Li, H.-fen, & Zhou, W.-ping. (2018). Early enforced mobilization after liver resection: A prospective randomized controlled trial. International Journal of Surgery, 54, 254–258. https://doi.org/10.1016/j.ijsu.2018.04.060
Lei, Y. T., Xie, J. W., Huang, Q., Huang, W., & Pei, F. X. (2021). Benefits of early   ambulation within 24 h after total knee arthroplasty: a multicenter retrospective cohort study in China. Military Medical Research, 8(1), 17. https://doi.org/10.1186/s40779-021-00310-x
Stethen, T. W., Ghazi, Y. A., Heidel, R. E., Daley, B. J., Barnes, L., Patterson, D., &   McLoughlin, J. M. (2018). Walking to recovery: the effects of missed ambulation events on postsurgical recovery after bowel resection. Journal of gastrointestinal oncology, 9(5), 953–961. 10.21037/jgo.2017.11.05
Yakkanti, R </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Edema and can you explain it in depth? [/INST] Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the bodys tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area may feel heavy, and joint stiffness. Other symptoms depend on the underlying cause.Causes may include venous insufficiency, heart failure, kidney problems, low protein levels, liver problems, deep vein thrombosis, infections, angioedema, certain medications, and lymphedema. It may also occur after prolonged sitting or standing and during menstruation or pregnancy. The condition is more concerning if it starts suddenly, or pain or shortness of breath is present.Treatment depends on the underlying cause. If the underlying mechanism involves sodium retention, decreased salt intake and a diuretic may be used. Elevating the legs and support stockings may be useful for edema of the legs. Older people are more commonly affected. The word is from the Greek οἴδημα oídēma meaning swelling.

Signs and symptoms
Specific area
An edema will occur in specific organs as part of inflammations, tendinitis or pancreatitis, for instance. Certain organs develop edema through tissue specific mechanisms. Examples of edema in specific organs:

Peripheral edema (dependent edema of legs) is extracellular fluid accumulation in the legs. This can occur in otherwise healthy people due to hypervolemia or maintaining a standing or seated posture for an extended period of time. It can occur due to diminished venous return of blood to the heart due to congestive heart failure or pulmonary hypertension. It can also occur in patients with increased hydrostatic venous pressure or decreased oncotic venous pressure, due to obstruction of lymphatic or venous vessels draining the lower extremity. Certain drugs (for example, amlodipine) can cause pedal edema.
Cerebral edema is extracellular fluid accumulation in the brain. It can occur in toxic or abnormal metabolic states and conditions such as systemic lupus or reduced oxygen at high altitudes. It causes drowsiness or loss of consciousness, leading to brain herniation and death.
Pulmonary edema occurs when the pressure in blood vessels in the lung is raised because of obstruction to the removal of blood via the pulmonary veins. This is usually due to failure of the left ventricle of the heart. It can also occur in altitude sickness or on inhalation of toxic chemicals. Pulmonary edema produces shortness of breath. Pleural effusions may occur when fluid also accumulates in the pleural cavity.
Edema may also be found in the cornea of the eye with glaucoma, severe conjunctivitis or keratitis or after  surgery. Affected people may perceive coloured haloes around bright lights.
Edema surrounding the eyes is called periorbital edema (puffy eyes) . The periorbital tissues are most noticeably swollen immediately after waking, perhaps as a result of the gravitational redistribution of fluid in the horizontal position.
Common appearances of cutaneous edema are observed with mosquito bites, spider bites, bee stings (wheal and flare), and skin contact with certain plants such as poison ivy or western poison oak, the latter of which are termed contact dermatitis.
Another cutaneous form of edema is myxedema, which is caused by increased deposition of connective tissue. In myxedema (and a variety of other rarer conditions) edema is caused by an increased tendency of the tissue to hold water within its extracellular space. In myxedema, this is due to  an increase in hydrophilic carbohydrate-rich molecules (perhaps mostly hyaluronin) deposited in the tissue matrix. Edema forms more easily in dependent areas in the elderly (sitting in chairs at home or on aeroplanes) and this is not well understood. Estrogens alter body weight in part through changes in tissue water content. There may be a variety of poorly understood situations in which transfer of water from tissue matrix to lymphatics is impaired because of changes in the hydrophilicity of the tissue or failure of the wicking function of terminal lymphatic capillaries.
In lymphedema, abnormal removal of interstitial fluid is caused by failure of the lymphatic system. This may be due to obstruction from, for example, pressure from a cancer or enlarged lymph nodes, destruction of lymph vessels by radiotherapy, or infiltration of the lymphatics by infection (such as elephantiasis). It is most commonly due to a failure of the pumping action of muscles due to immobility, most strikingly in conditions such as multiple sclerosis, or paraplegia. It has been suggested that the edema that occurs in some people following use of aspirin-like cyclo-oxygenase inhibitors such as ibuprofen or indomethacin may be due to inhibition of lymph heart action.

Generalized
A rise in hydrostatic pressure occurs in cardiac failure. A fall in osmotic pressure occurs in nephrotic syndrome and liver failure.Causes of edema which are generalized to the whole body can cause edema in multiple organs and peripherally. For example, severe heart failure can cause pulmonary edema, pleural effusions, ascites and peripheral edema. Such severe systemic edema is called anasarca. In rare cases, a parvovirus B19 infection may cause generalized edemas.Although a low plasma oncotic pressure is widely cited for the edema of nephrotic syndrome, most physicians note that the edema may occur before there is any significant protein in the urine (proteinuria) or fall in plasma protein level. Most forms of nephrotic syndrome are due to biochemical and structural changes in the basement membrane of capillaries in the kidney glomeruli, and these changes occur, if to a lesser degree, in the vessels of most other tissues of the body. Thus the resulting increase in permeability that leads to protein in the urine can explain the edema if all other vessels are more permeable as well.As well as the previously mentioned conditions, edemas often occur during the late stages of pregnancy in some women. This is more common with those of a history of pulmonary problems or poor circulation also being intensified if arthritis is already present in that particular woman. Women who already have arthritic problems most often have to seek medical help for pain caused from over-reactive swelling. Edemas that occur during pregnancy are usually found in the lower part of the leg, usually from the calf down.
Hydrops fetalis is a condition in a baby characterized by an accumulation of fluid in at least two body compartments.

Cause
Heart
The pumping force of the heart should help to keep a normal pressure within the blood vessels. But if the heart begins to fail (a condition known as congestive heart failure) the pressure changes can cause very severe water retention. In this condition water retention is mostly visible in the legs, feet and ankles, but water also collects in the lungs, where it causes a chronic cough. This condition is usually treated with diuretics; otherwise, the water retention may cause breathing problems and additional stress on the heart.

Kidneys
Another cause of severe water retention is kidney failure, where the kidneys are no longer able to filter fluid out of the blood and turn it into urine. Kidney disease often starts with inflammation, for instance in the case of diseases such as nephrotic syndrome or lupus. This type of water retention is usually visible in the form of swollen legs and ankles.

Protein
Protein attracts water and plays an important role in water balance. In cases of severe protein deficiency, the blood may not contain enough protein to attract water from the tissue spaces back into the capillaries. This is why starvation often shows an enlarged abdomen. The abdomen is swollen with edema or water retention caused by the lack of protein in the diet.When the capillary walls are too permeable, protein can leak out of the blood and settle in the tissue spaces. It will then act like a magnet for water, continuously attracting more water from the blood to accumulate in the tissue spaces.

Others
Swollen legs, feet and ankles are common in late pregnancy. The problem is partly caused by the weight of the uterus on the major veins of the pelvis. It usually clears up after delivery of the baby, and is mostly not a cause for concern, though it should always be reported to a doctor.
Lack of exercise is another common cause of water retention in the legs. Exercise helps the leg veins work against gravity to return blood to the heart. If blood travels too slowly and starts to pool in the leg veins, the pressure can force too much fluid out of the leg capillaries into the tissue spaces. The capillaries may break, leaving small blood marks under the skin. The veins themselves can become swollen, painful and distorted – a condition known as varicose veins. Muscle action is needed not only to keep blood flowing through the veins but also to stimulate the lymphatic system to fulfil its "overflow" function. Long-haul flights, lengthy bed-rest, immobility caused by disability and so on, are all potential causes of water retention. Even very small exercises such as rotating ankles and wiggling toes can help to reduce it.Certain medications are prone to causing water retention. These include estrogens, thereby including drugs for hormone replacement therapy or the combined oral contraceptive pill, as well as non-steroidal anti-inflammatory drugs and beta-blockers.Premenstrual water retention, causing bloating and breast tenderness, is common.

Mechanism
Six factors can contribute to the formation of edema:
increased hydrostatic pressure;
reduced colloidal or oncotic pressure within blood vessels;
increased tissue colloidal or  oncotic pressure;
increased blood vessel wall permeability (such as inflammation);
obstruction of fluid clearance in the lymphatic system;
changes in the water-retaining properties of the tissues themselves. Raised hydrostatic pressure often reflects retention of water and sodium by the kidneys.Generation of interstitial fluid is regulated by the forces of the Starling equation. Hydrostatic pressure within blood vessels tends to cause water to filter out into the tissue. This leads to a difference in protein concentration between blood plasma and tissue. As a result, the colloidal or oncotic pressure of the higher level of protein in the plasma tends to draw water back into the blood vessels from the tissue. Starlings equation states that the rate of leakage of fluid is determined by the difference between the two forces and also by the permeability of the vessel wall to water, which determines the rate of flow for a given force imbalance. Most water leakage occurs in capillaries or post capillary venules, which have a semi-permeable membrane wall that allows water to pass more freely than protein </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Sinus and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Myokymia and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Acute promyelocytic leukemia and can you explain it in depth? [/INST] Acute promyelocytic leukemia (APML, APL) is a subtype of acute myeloid leukemia (AML), a cancer of the white blood cells. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes.  The disease is characterized by a chromosomal translocation involving the retinoic acid receptor alpha (RARA) gene and is distinguished from other forms of AML by its responsiveness to all-trans retinoic acid (ATRA; also known as tretinoin) therapy. Acute promyelocytic leukemia was first characterized in 1957 by French and Norwegian physicians as a hyperacute fatal illness, with a median survival time of less than a week. Today, prognoses have drastically improved; 10-year survival rates are estimated to be approximately 80-90% according to one study.

Signs and symptoms
The symptoms tend to be similar to AML in general with the following being possible symptoms:

Easy bleeding from low platelets may include:

Bruising (ecchymosis)
Gingival bleeding
Nose bleeds (epistaxis)
Increased menstrual bleeding (menorrhagia)
Brain bleed (intracerebral hemorrhage)

Pathogenesis
Acute promyelocytic leukemia is characterized by a chromosomal translocation involving the retinoic acid receptor alpha (RARA) gene on chromosome 17. In 95% of cases of APL, the RARA gene on chromosome 17 is involved in a reciprocal translocation with the promyelocytic leukemia gene (PML) on chromosome 15, a translocation denoted as t(15;17)(q24;q21). The RAR receptor is dependent on retinoic acid for regulation of transcription.Eight other rare gene rearrangements have been described in APL fusing RARA to promyelocytic leukemia zinc finger (PLZF), nucleophosmin, nuclear matrix associated, signal transducer and activator of transcription 5b (STAT5B), protein kinase A regulatory subunit 1α (PRKAR1A), factor interacting with PAPOLA and CPSF1 (FIP1L1), BCL-6 corepressor or oligonucleotide/oligosaccharide-binding fold containing 2A (NABP1) genes. Some of these rearrangements are ATRA-sensitive or have unknown sensitivity to ATRA because they are so rare; STAT5B/RARA and PLZF/RARA are known to be resistant to ATRA.The fusion of PML and RARA results in expression of a hybrid protein with altered functions. This fusion protein binds with enhanced affinity to sites on the cells DNA, blocking transcription and differentiation of granulocytes. It does so by enhancing interaction of nuclear co-repressor (NCOR) molecule and histone deacetylase (HDAC). Although the chromosomal translocation involving RARA is believed to be the initiating event, additional mutations are required for the development of leukemia.RARA/PLZF gene fusion produces a subtype of APL that is unresponsive to tretinoin therapy and less responsive to standard anthracycline chemotherapy hence leading to poorer long-term outcomes in this subset of patients.

Diagnosis
Acute promyelocytic leukemia can be distinguished from other types of AML based on microscopic examination of the blood film or a bone marrow aspirate or biopsy as well as finding the characteristic rearrangement. The presence of promyelocytes containing multiple Auer rods (termed faggot cells) on the peripheral blood smear is highly suggestive of acute promyelocytic leukemia. Definitive diagnosis requires testing for the PML/RARA fusion gene. This may be done by polymerase chain reaction (PCR), fluorescence in situ hybridization, or conventional cytogenetics of peripheral blood or bone marrow. This mutation involves a translocation of the long arm of chromosomes 15 and 17. On rare occasions, a cryptic translocation may occur which cannot be detected by cytogenetic testing; on these occasions PCR testing is essential to confirm the diagnosis.

Treatment
Initial treatment
APL is unique among leukemias due to its sensitivity to all-trans retinoic acid (ATRA; tretinoin), the acid form of vitamin A. Treatment with ATRA dissociates the NCOR-HDACL complex from RAR and allows DNA transcription and differentiation of the immature leukemic promyelocytes into mature granulocytes by targeting the oncogenic transcription factor and its aberrant action. Unlike other chemotherapies, ATRA does not directly kill the malignant cells.  ATRA induces the terminal differentiation of the leukemic promyelocytes, after which these differentiated malignant cells undergo spontaneous apoptosis on their own. ATRA alone is capable of inducing remission but it is short-lived in the absence of concurrent "traditional" chemotherapy. As of 2013 the standard of treatment for concurrent chemotherapy has become arsenic trioxide, which combined with ATRA is referred to ATRA-ATO; before 2013 the standard of treatment was anthracycline (e.g. daunorubicin, doxorubicin, idarubicin or mitoxantrone)-based chemotherapy. Both chemotherapies result in a clinical remission in approximately 90% of patients with arsenic trioxide having a more favorable side effect profile.ATRA therapy is associated with the unique side effect of differentiation syndrome. This is associated with the development of dyspnea, fever, weight gain, peripheral edema and is treated with dexamethasone. The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome from cytokine release from the differentiating promyelocytes.The monoclonal antibody, gemtuzumab ozogamicin, has been used successfully as a treatment for APL, although it has been withdrawn from the US market due to concerns regarding potential toxicity of the drug and it is not currently marketed in Australia, Canada or the UK. Given in conjunction with ATRA, it produces a response in around 84% of patients with APL, which is comparable to the rate seen in patients treated with ATRA and anthracycline-based therapy. It produces less cardiotoxicity than anthracycline-based treatments and hence may be preferable in these patients.

Maintenance therapy
After stable remission was induced, the standard of care previously was to undergo 2 years of maintenance chemotherapy with methotrexate, mercaptopurine and ATRA. A significant portion of patients relapsed without consolidation therapy. In the 2000 European APL study, the 2-year relapse rate for those that did not receive consolidation chemotherapy (ATRA not included) therapy was 27% compared to 11% in those that did receive consolidation therapy (p<0.01). Likewise in the 2000 US APL study, the survival rates in those receiving ATRA maintenance was 61% compared to just 36% without ATRA maintenance.However, recent research on consolidation therapy following ATRA-ATO, which became the standard treatment in 2013, has found that maintenance therapy in low-risk patients following this therapy may be unnecessary, although this is controversial.

Relapsed or refractory disease
Arsenic trioxide (As2O3) is currently being evaluated for treatment of relapsed/refractory disease. Remission with arsenic trioxide has been reported.
Studies have shown arsenic reorganizes nuclear bodies and degrades the mutant PML-RAR fusion protein. Arsenic also increases caspase activity which then induces apoptosis. It does reduce the relapse rate for high risk patients. In Japan a synthetic retinoid, tamibarotene, is licensed for use as a treatment for ATRA-resistant APL.

Investigational agents
Some evidence supports the potential therapeutic utility of histone deacetylase inhibitors such as valproic acid or vorinostat in treating APL. According to one study, a cinnamon extract has effect on the apoptotic process in acute myeloid leukemia HL-60 cells.

Prognosis
Prognosis is generally good relative to other leukemias. Because of the acuteness of onset compared to other leukemias, early death is comparatively more common. If untreated, it has median survival of less than a month. It has been transformed from a highly fatal disease to a highly curable one. The cause of early death is most commonly severe bleeding, often intracranial hemorrhage. Early death from hemorrhage occurs in 5–10% of patients in countries with adequate access to healthcare and 20–30% of patients in less developed countries. Risk factors for early death due to hemorrhage include delayed diagnosis, late treatment initiation, and high white blood cell count on admission. Despite advances in treatment, early death rates have remained relatively constant, as described by several groups including Scott McClellan, Bruno Medeiros, and Ash Alizadeh at Stanford University.Relapse rates are extremely low. Most deaths following remission are from other causes, such as second malignancies, which in one study occurred in 8% of patients. In this study, second malignancies accounted for 41% of deaths, and heart disease, 29%. Survival rates were 88% at 6.3 years and 82% at 7.9 years.In another study, 10-year survival rate was estimated to be approximately 77%.

Epidemiology
Acute promyelocytic leukemia represents 10–12% of AML cases. The median age is approximately 30–40 years, which is considerably younger than the other subtypes of AML (70 years), however in elderly population APL has peculiar characteristics. Incidence is higher among individuals of Latin American or South European origin. It can also occur as a secondary malignancy in those that receive treatment with topoisomerase II inhibitors (such as the anthracyclines and etoposide) due to the carcinogenic effects of these agents, with patients with breast cancer representing the majority of such patients. Around 40% of patients with APL also have a chromosomal abnormality such as trisomy 8 or isochromosome 17 which do not appear to impact on long-term outcomes.

References
External links

Sanz, Miguel A.; Grimwade, David; Tallman, Martin S.; Lowenberg, Bob; Fenaux, Pierre; Estey, Elihu H.; Naoe, Tomoki; Lengfelder, Eva; Büchner, Thomas; Döhner, Hartmut; Burnett, Alan K.; Lo-Coco, Francesco (2009) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Post-void dribbling and can you explain it in depth? [/INST]  </s>


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<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cough and can you explain it in depth? [/INST] A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three phases: an inhalation, a forced exhalation against a closed glottis, and a violent release of air from the lungs following opening of the glottis, usually accompanied by a distinctive sound.Frequent coughing usually indicates the presence of a disease. Many viruses and bacteria benefit, from an evolutionary perspective, by causing the host to cough, which helps to spread the disease to new hosts. Most of the time, irregular coughing is caused by a respiratory tract infection but can also be triggered by choking, smoking, air pollution, asthma, gastroesophageal reflux disease, post-nasal drip, chronic bronchitis, lung tumors, heart failure and medications such as angiotensin-converting-enzyme inhibitors (ACE inhibitors).
Treatment should target the cause; for example, smoking cessation or discontinuing ACE inhibitors.  Cough suppressants such as codeine or dextromethorphan are frequently prescribed, but have been demonstrated to have little effect. Other treatment options may target airway inflammation or may promote mucus expectoration. As it is a natural protective reflex, suppressing the cough reflex might have damaging effects, especially if the cough is productive.

Presentation
Complications
The complications of coughing can be classified as either acute or chronic. Acute complications include cough syncope (fainting spells due to decreased blood flow to the brain when coughs are prolonged and forceful), insomnia, cough-induced vomiting, subconjunctival hemorrhage or "red eye", coughing defecation and in women with a prolapsed uterus, cough urination.  Chronic complications are common and include abdominal or pelvic hernias, fatigue fractures of lower ribs and costochondritis. Chronic or violent coughing can contribute to damage to the pelvic floor and a possible cystocele.

Differential diagnosis
A cough in children may be either a normal physiological reflex or due to an underlying cause. In healthy children it may be normal in the absence of any disease to cough ten times a day. The most common cause of an acute or subacute cough is a viral respiratory tract infection. A healthy adult also coughs 18.8 times a day on average, but in the population with respiratory disease the geometric mean frequency is 275 times a day. In adults with a chronic cough, i.e. a cough longer than 8 weeks, more than 90% of cases are due to post-nasal drip, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease. The causes of chronic cough are similar in children with the addition of bacterial bronchitis.

Infections
A cough can be the result of a respiratory tract infection such as the common cold, COVID-19, acute bronchitis, pneumonia, pertussis, or tuberculosis. In the vast majority of cases, acute coughs, i.e. coughs shorter than 3 weeks, are due to the common cold. In people with a normal chest X-ray, tuberculosis is a rare finding. Pertussis is increasingly being recognised as a cause of troublesome coughing in adults.
After a respiratory tract infection has cleared, the person may be left with a postinfectious cough. This typically is a dry, non-productive cough that produces no phlegm. Symptoms may include a tightness in the chest, and a tickle in the throat. This cough may often persist for weeks after an illness. The cause of the cough may be inflammation similar to that observed in repetitive stress disorders such as carpal tunnel syndrome. The repetition of coughing produces inflammation which produces discomfort, which in turn produces more coughing. Postinfectious cough typically does not respond to conventional cough treatments. Treatment consists of any anti-inflammatory medicine (such as ipratropium) to treat the inflammation, and a cough suppressant to reduce frequency of the cough until inflammation clears. Inflammation may increase sensitivity to other existing issues such as allergies, and treatment of other causes of coughs (such as use of an air purifier or allergy medicines) may help speed recovery.

Reactive airway disease
When coughing is the only complaint of a person who meets the criteria for asthma (bronchial hyperresponsiveness and reversibility), this is termed cough-variant asthma. Atopic cough and eosinophilic bronchitis are related conditions. Atopic cough occurs in individuals with a family history of atopy (an allergic condition), abundant eosinophils in the sputum, but with normal airway function and responsiveness. Eosinophilic bronchitis is characterized by eosinophils in sputum and in bronchoalveolar lavage fluid without airway hyperresponsiveness or an atopic background. This condition responds to treatment with corticosteroids. Cough can also worsen in an acute exacerbation of chronic obstructive pulmonary disease.
Asthma is a common cause of chronic cough in adults and children. Coughing may be the only symptom the person has from their asthma, or asthma symptoms may also include wheezing, shortness of breath, and a tight feeling in their chest. Depending on how severe the asthma is, it can be treated with bronchodilators (medicine which causes the airways to open up) or inhaled steroids. Treatment of the asthma should make the cough go away.
Chronic bronchitis is defined clinically as a persistent cough that produces sputum (phlegm) and mucus, for at least three months in two consecutive years. Chronic bronchitis is often the cause of "smokers cough". The tobacco smoke causes inflammation, secretion of mucus into the airway, and difficulty clearing that mucus out of the airways. Coughing helps clear those secretions out. May be treated by quitting smoking. May also be caused by pneumoconiosis and long-term fume inhalation.

Gastroesophageal reflux
In people with unexplained cough, gastroesophageal reflux disease should be considered. This occurs when acidic contents of the stomach come back up into the esophagus. Symptoms usually associated with GERD include heartburn, sour taste in the mouth, or a feeling of acid reflux in the chest, although, more than half of the people with cough from GERD dont have any other symptoms. An esophageal pH monitor can confirm the diagnosis of GERD. Sometimes GERD can complicate respiratory ailments related to cough, such as asthma or bronchitis. The treatment involves anti-acid medications and lifestyle changes with surgery indicated in cases not manageable with conservative measures.

Air pollution
Coughing may be caused by air pollution including tobacco smoke, particulate matter, irritant gases, and dampness in a home.
The human health effects of poor air quality are far reaching, but principally affect the bodys respiratory system and the cardiovascular system.  Individual reactions to air pollutants depend on the type of pollutant a person is exposed to, the degree of exposure, the individuals health status and genetics.  People who exercise outdoors on hot, smoggy days, for example, increase their exposure to pollutants in the air.

Foreign body
A foreign body can sometimes be suspected, for example if the cough started suddenly when the patient was eating. Rarely, sutures left behind inside the airway branches can cause coughing. A cough can be triggered by dryness from mouth breathing or recurrent aspiration of food into the windpipe in people with swallowing difficulties.

Angiotensin-converting enzyme inhibitor
ACE inhibitors are drugs often used to treat high blood pressure that can sometimes be the cause of a cough as a side effect, and stopping their use will stop the cough.

Tic cough
A tic cough, previously called a habit cough, is one that responds to behavioral or psychiatric therapy after organic causes have been excluded. Absence of the cough during sleep is common, but not diagnostic. A tic cough is thought to be more common in children than in adults.
A similar disorder is the somatic cough syndrome previously called the psychogenic cough.

Neurogenic cough
Some cases of chronic cough may be attributed to a sensory neuropathic disorder. Treatment for neurogenic cough may include the use of certain neuralgia medications.  Coughing may occur in tic disorders such as Tourette syndrome, although it should be distinguished from throat-clearing in this disorder.

Other
Cough may also be caused by conditions affecting the lung tissue such as bronchiectasis, cystic fibrosis, interstitial lung diseases and sarcoidosis. Coughing can also be triggered by benign or malignant lung tumors or mediastinal masses. Through irritation of the nerve, diseases of the external auditory canal (wax, for example) can also cause cough. Cardiovascular diseases associated with cough are heart failure, pulmonary infarction and aortic aneurysm. Nocturnal cough is associated with heart failure, as the heart does not compensate for the increased volume shift to the pulmonary circulation, in turn causing pulmonary edema and resultant cough. Other causes of nocturnal cough include asthma, post-nasal drip and gastroesophageal reflux disease (GERD). Another cause of cough occurring preferentially in supine position is recurrent aspiration.Given its irritant nature to mammal tissues, capsaicin is widely used to determine the cough threshold and as a tussive stimulant in clinical research of cough suppressants. Capsaicin is what makes chili peppers spicy, and might explain why workers in factories with these fruits can develop a cough.
Coughing may also be used for social reasons, and as such is not always involuntary. A voluntary cough, often written as "ahem",  can be used to attract attention or express displeasure, as a form of nonverbal, paralingual metacommunication.

Airway clearance
Coughing, and huffing are important ways of removing mucus as sputum in many conditions such as cystic fibrosis, and chronic bronchitis.

Pathophysiology
A cough is a protective reflex in healthy individuals which is influenced by psychological factors. The cough reflex is initiated by stimulation of two different classes of afferent nerves, namely the myelinated rapidly adapting receptors, and nonmyelinated C-fibers with endings in the lung.

Diagnostic approach
The type of cough may help in the diagnosis. For instance, an inspiratory "whooping" sound on coughing almost doubles the likelihood that the illness is pertussis.
Blood may occur in small amounts with severe cough of many causes, but larger amounts suggests bronchitis, bronchiectasis, tuberculosis, or primary lung cancer.Further workup may include labs, x-rays, and spirometry.

Classification
A cough can be classified by its duration, character, quality, and timing. The duration can be either acute (of sudden onset) if it is present less than three weeks, subacute if it is present between three or eight weeks, and chronic when lasting longer than eight weeks. A cough can be non-productive (dry) or productive (when phlegm is produced that may be coughed up as sputum). It may occur only at night (then called nocturnal cough), during both night and day, or just during the day.A number of characteristic coughs exist. While these have not been found to be diagnostically useful in adults, they are of use in children. A barky cough is part of the common presentation of croup. A staccato cough has been classically described with neonatal chlamydial pneumonia.

Treatment
The treatment of a cough in children is based on the underlying cause. In children half of cases go away without treatment in 10 days and 90% in 25 days.According to the American Academy of Pediatrics the use of cough medicine to relieve cough symptoms is supported by little evidence and thus not recommended for treating cough symptoms in children. There is tentative evidence that the use of honey is better than no treatment or diphenhydramine in decreasing coughing. It does not alleviate coughing to the same extent as dextromethorphan but it shortens the cough duration better than placebo and salbutamol. A trial of antibiotics or inhaled corticosteroids may be tried in children with a chronic cough in an attempt to treat protracted bacterial bronchitis or asthma respectively. There is insufficient evidence to recommend treating children who have a cough that is not related to a specific condition with inhaled anti-cholinergics.Because coughing can spread disease through infectious aerosol droplets, it is recommended to cover ones mouth and nose with the forearm, the inside of the elbow, a tissue or a handkerchief while coughing.

Epidemiology
A cough is the most common reason for visiting a primary care physician in the United States.

Other animals
Marine mammals such as dolphins and whales cannot cough </s>