Answer: Myofibroblasts

Fibroblasts are a type of cell which have mesenchymal origin and can exhibit either non-contractile or highly contractile phenotype. Under normal conditions, fibroblasts function to maintain tissue homeostasis by regulating the turnover of extracellular matrix (ECM). When tissues are injured, however, fibroblasts around the injured region differentiate into myofibroblasts, a type of highly contractile cells that produce abundant ECM proteins. While the mechanisms of wound healing are not completely understood, it has become clear that both fibroblasts and myofibroblasts play a critical role in the wound healing process. Specifically, the traction forces of fibroblasts and coordinated contraction of myofibroblasts are believed to be responsible for wound contraction and closure. However, excessive myofibroblast activity, accompanied by elevated levels of mechanical stress in the healing region, often causes scar tissue formation, and in the worst case, contracture of tissues (e.g. Dupuytren’s contracture), leading to local immobilization and loss of function.

Torsade de pointes is an uncommon and distinctive form of polymorphic ventricular tachycardia (VT) characterized by a gradual change in the amplitude and twisting of the QRS complexes around the isoelectric line. Torsade de pointes, often referred to as torsade, is associated with a prolonged QT interval, which may be congenital or acquired. Torsade usually terminates spontaneously but frequently recurs and may degenerate into ventricular fibrillation. This woman is likely to have hypokalaemia and hypomagnesaemia as a result of vomiting. In addition to this, the erythromycin will predispose her to torsades de pointes. The patient should be given Magnesium 2g over 10 minutes. Knowledge of the management of this peri arrest diagnosis is hence important in surgical practice.

Answer: Aspirin

Aspirin increases bleeding time when taken orally. Aspirin causes several different effects in the body, mainly the reduction of inflammation, analgesia (relief of pain), the prevention of clotting, and the reduction of fever. Much of this is believed to be due to decreased production of prostaglandins and TXA2. Aspirin’s ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Prostaglandins are local chemical messengers that exert multiple effects including but not limited to the transmission of pain information to the brain, modulation of the hypothalamic thermostat, and inflammation. They are produced in response to the stimulation of phospholipids within the plasma membrane of cells resulting in the release of arachidonic acid (prostaglandin precursor). Thromboxanes are responsible for the aggregation of platelets that form blood clots.
Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation.

Antihypertensive and antidiabetic medications do not need to be stopped when a patient is undergoing local anaesthesia. Steroid (Prednisolone) use cannot be stopped abruptly; tapering the drug gives the adrenal glands time to return to their normal patterns of secretion. Withdrawal symptoms and signs (weakness, fatigue, decreased appetite, weight loss, nausea, vomiting, diarrhoea, abdominal pain) can mimic many other medical problems. Some may be life-threatening.

Complications of Transurethral Resection: TURP
T URP syndrome
U rethral stricture/UTI
R etrograde ejaculation
P erforation of the prostate

TURP syndrome can cause a wide variety of symptoms that include asymptomatic hyponatremia, ECG changes, fatigue, vomiting, confusion, visual loss, coma and death. In a conscious and alert patient, changes in the mental state of may be the first sign of TURP syndrome and bladder perforation.

A below-knee amputation (“BKA”) is a transtibial amputation that involves removing the foot, ankle joint, and distal tibia and fibula with related soft tissue structures. In general, a BKA is preferred over an above-knee amputation (AKA), as the former has better rehabilitation and functional outcomes. There are three major categories of indications for proceeding with a BKA. These include:
– Urgent cases where source control of necrotizing infections or haemorrhagic injuries outweighs limb preservation.
– Less acutely, urgent BKAs may be performed for chronic nonhealing ulcers or significant infections with the risk of impending systemic infection or sepsis.
– Urgent BKAs may be performed where limb salvage has failed to preserve a mangled lower extremity. Adequate resuscitation and stabilization must always have occurred before such a decision, as judged by vital signs, lactate, base deficit, and the management of concomitant injuries.
This man is hemodynamically unstable and the limb is likely to be non-viable after so many hours of entrapment. Hence, the safest option would be primary amputation of the injured limb.

Because of the substantial risk of thromboembolism early after valve replacement, perioperative initiation of anticoagulation is necessary, despite the increased risk for bleeding. Anticoagulation should be initiated within 24 h after the procedure with unfractionated heparin or low-molecular-weight heparin (LMWH).
Heparin is monitored by checking the activated partial thromboplastin time or anti-Xa activity.
Oral anticoagulants are monitored by INR.

Answer: Escharotomy

Escharotomy is the surgical division of the nonviable eschar, which allows the cutaneous envelope to become more compliant. Hence, the underlying tissues have an increased available volume to expand into, preventing further tissue injury or functional compromise.

Full-thickness circumferential and near-circumferential skin burns result in the formation of a tough, inelastic mass of burnt tissue (eschar). The eschar, by virtue of this inelasticity, results in the burn-induced compartment syndrome. This is caused by the accumulation of extracellular and extravascular fluid within confined anatomic spaces of the extremities or digits. The excessive fluid causes the intracompartmental pressures to increase, resulting in collapse of the contained vascular and lymphatic structures and, hence, loss of tissue viability. The capillary closure pressure of 30 mm Hg, also measured as the compartment pressure, is accepted as that which requires intervention to prevent tissue death.

The circumferential eschar over the torso can lead to significant compromise of chest wall excursions and can hinder ventilation. Abdominal compartment syndrome with visceral hypoperfusion is associated with severe burns of the abdomen and torso. (A literature review by Strang et al found the prevalence of abdominal compartment syndrome in severely burned patients to be 4.1-16.6%, with the mean mortality rate for this condition in these patients to be 74.8%). Similarly, airway patency and venous return may be compromised by circumferential burns involving the neck.

Performing an escharotomy will therefore improve ventilation.

There is a substantial risk of hypoglycaemia in neonates following surgery, therefore 10% dextrose should be administered to them to avoid the complications associated with hypoglycaemia.

Answer: Bradycardia

Prolonged bed rest and immobilization inevitably lead to complications. Such complications are much easier to prevent than to treat. Musculoskeletal complications include loss of muscle strength and endurance, contractures and soft tissue changes, disuse osteoporosis, and degenerative joint disease. Cardiovascular complications include an increased heart rate (tachycardia), decreased cardiac reserve, orthostatic hypotension, and venous thromboembolism.

This patient has a Bankart lesion which is the most common underlying abnormality in recurrent anterior dislocation of the shoulder.

Bankart lesion is an injury of the anterior (inferior) glenoid labrum of the shoulder due to anterior shoulder dislocation. When this happens, a pocket at the front of the glenoid forms that allows the humeral head to dislocate into it. It is usually visualised by CT and MRI scanning and is often repaired arthroscopically.

Shoulder fractures and dislocations usually result from low-energy falls in predominantly elderly females or from high-energy trauma in young males. They can be associated with nerve injury (commonly axillary), and fracture-dislocation of the humeral head. Anterior shoulder dislocation (glenohumeral dislocation) is the most common type of shoulder dislocation (>90%) and is usually traumatic in nature.

Early assessment of shoulder dislocation:
Careful history, examination, and documentation of neurovascular status of the upper limb, in particular the axillary nerve, is important. This should be re-assessed after manipulation. Early radiographs should also be done to confirm the direction of the dislocation.

Initial management of anterior dislocation:
It consists of emergent closed reduction (to prevent lasting chondral damage) under Entonox and analgesia, but often requires conscious sedation. The affected arm should then be immobilised in a polysling. Initial management requires emergent reduction to prevent lasting chondral damage.

There is strong evidence to support haemostatic resuscitation in the setting of massive haemorrhage due to trauma. This advocates the use of 1:1:1 ratio.

Uncontrolled haemorrhage accounts for up to 39% of all trauma-related deaths. In the UK, approximately 2% of all trauma patients need massive transfusion. Massive transfusion is defined as the replacement of a patient’s total blood volume in less than 24 hours or the acute administration of more than half the patient’s estimated blood volume per hour. During acute bleeding, the practice of haemostatic resuscitation has been shown to reduce mortality rates. It is based on the principle of transfusion of blood components in fixed ratios. For example, packed red cells, FFP, and platelets are administered in a ratio of 1:1:1.

The wound of this patient should be packed with alginate dressing. Abscess wounds should not undergo primary closure. Moreover, use of gauze is inappropriate and would be difficult to redress.

Alginate dressings are absorbent wound care products that contain sodium and calcium fibres derived from seaweed. An individual dressing is able to absorb up to 20 times its own weight. These dressings, which are easy to use, mold themselves to the shape of the wound, which helps ensure that they absorb wound drainage properly. In abscesses requiring incision and drainage, alginate dressings are well-tolerated and their removal causes minimal pain.

Absence of comorbidities and a small procedure with no likelihood of systemic compromise will equate to an ASA score of 1.

The ASA physical status classification system is a system for assessing the fitness of patients before surgery. It has six grades, as described below:

ASA 1: No physiological, biochemical, or psychiatric disturbance. The surgical pathology is localised and has not invoked systemic disturbance.

ASA 2: Mild or moderate systemic disruption caused either by the surgical disease process or through an underlying pre-existing disease.

ASA 3: Severe systemic disruption, not life-threatening, caused either by the surgical pathology or a pre-existing disease.

ASA 4: Patient has severe systemic disease that is a constant threat to life.

ASA 5: Patient is moribund and will not survive without surgery.

ASA 6: A brain-dead patient whose organs are being removed with the intention of transplanting them into another patient.

Patients with burns of more than 20% – 25% of their body surface should be managed with aggressive IV fluid resuscitation to prevent “burn shock.
Rule of 9’s for Adults: 9% for each arm, 18% for each leg, 9% for head,18% for front torso, 18% for back torso.
A variety of formulas exist, like Brooke, Galveston, Rule of Ten, but the most common formula is the Parkland Formula. This formula estimates the amount of fluid given in the first 24 hours, starting from the time of the burn.
Four mL lactated ringers solution × percentage total body surface area (%TBSA) burned × patient’s weight in kilograms = total amount of fluid given in the first 24 hours.
One-half of this fluid should be given in the first eight hours.
For example, a 75 kg patient with 55% total body surface area burn would need; 4 mL LR × 75kg × 55% TBSA = 16,500 mL in the first 24 hours, with 8,250 mL in the first eight hours or approximately 1 litre/hr for the first eight hours.
For paediatric patients, the Parkland Formula can be used plus the addition of normal maintenance fluids added to the total.
Whichever formula is used, the important point to remember is the fluid amount calculated is just a guideline. Patient’s vital signs, mental status, capillary refill and urine output must be monitored and fluid rates adjusted accordingly. Urine output of 0.5 mL/kg or about 30 – 50 mL/hr in adults and 0.5-1.0 mL/kg/hr in children less than 30kg is a good target for adequate fluid resuscitation.
Other management for severe burns includes nasal gastric tube placement as most patients will develop ileus. Foley catheters should be placed to monitor urine output. Cardiac and pulse oximetry monitoring is indicated. Pain control is best managed with IV medication. Finally, burns are considered tetanus-prone wounds and tetanus prophylaxis are indicated if not given in the past five years. In any severe flame burn, you should always consider possible associated inhalation injury, carbon monoxide or cyanide poisoning.

This wound should be managed by primary closure as there is minimal associated tissue loss and the surgery is minor and uncontaminated.

Primary wound closure is the fastest type of closures, and is also known as healing by primary intention. Wounds that heal by primary closure have a small, clean defect that minimizes the risk of infection and requires new blood vessels and keratinocytes to migrate only a small distance. Standard methods of suturing are usually sufficient for primary wound closure.

Based on the history and findings, the most likely causative organism is cryptosporidium. It can cause severe, chronic, and possibly fatal diarrhoea in immunocompromised patients.

In patients with HIV/AIDS, clinical manifestations of cryptosporidiosis vary with the degree of immune compromise. Those with CD4 cell counts above 180–200/μL may be asymptomatic or develop self-limiting diarrhoeal illness. However, patients with advanced AIDS (CD4 cell counts <50/μL) can have severe diarrhoea that can persist for several months, resulting in severe dehydration, weight loss and malnutrition, extended hospitalizations, and mortality. In addition, patients with advanced AIDS are at greater risk of developing extraintestinal infection, particularly of the biliary, pancreatic, and respiratory tracts.

Answer: Flail chest injury

Flail chest is a life-threatening medical condition that occurs when a segment of the rib cage breaks due to trauma and becomes detached from the rest of the chest wall. Two of the symptoms of flail chest are chest pain and shortness of breath.

It occurs when multiple adjacent ribs are broken in multiple places, separating a segment, so a part of the chest wall moves independently. The number of ribs that must be broken varies by differing definitions: some sources say at least two adjacent ribs are broken in at least two places, some require three or more ribs in two or more places. The flail segment moves in the opposite direction to the rest of the chest wall: because of the ambient pressure in comparison to the pressure inside the lungs, it goes in while the rest of the chest is moving out, and vice versa. This so-called paradoxical breathing is painful and increases the work involved in breathing.

Flail chest is usually accompanied by a pulmonary contusion, a bruise of the lung tissue that can interfere with blood oxygenation. Often, it is the contusion, not the flail segment, that is the main cause of respiratory problems in people with both injuries.

Surgery to fix the fractures appears to result in better outcomes.

Answer: Beta 2 transferrin assay

Beta-2-transferrin is a protein found only in CSF and perilymph. Since 1979, beta-2-transferrin has been used extensively by otolaryngologists in the diagnosis of CSF rhinorrhoea and skull-base cerebrospinal fluid fistulas. With sensitivity of 94% – 100%, and specificity of 98% – 100%, this assay has become the gold standard in detection of CSF leakage. CSF rhinorrhoea is characterized by clear or xanthochromic watery rhinorrhoea that may not become apparent until nasal packing is removed.

Answer: Achalasia

Achalasia is a primary oesophageal motility disorder characterized by the absence of oesophageal peristalsis and impaired relaxation of the lower oesophageal sphincter (LES) in response to swallowing. The LES is hypertensive in about 50% of patients. These abnormalities cause a functional obstruction at the gastroesophageal junction (GEJ).
Symptoms of achalasia include the following:

Dysphagia (most common)

Regurgitation

Chest pain (behind the sternum)

Heartburn

Weight loss

Physical examination is non-contributory.

Treatment recommendations are as follows:

Initial therapy should be either graded pneumatic dilation (PD) or laparoscopic surgical myotomy with a partial fundoplication in patients fit to undergo surgery

Procedures should be performed in high-volume centres of excellence

Initial therapy choice should be based on patient age, sex, preference, and local institutional expertise

Botulinum toxin therapy is recommended for patients not suited to PD or surgery

Pharmacologic therapy can be used for patients not undergoing PD or myotomy and who have failed botulinum toxin therapy (nitrates and calcium channel blockers most common).

The invasion of the oesophageal neural plexus by the tumour can cause nonrelaxation of the LES, thus mimicking achalasia. This condition is known as malignant pseudo achalasia. Since contrast radiography and endoscopy frequently fail to differentiate these 2 entities, patients with a presumed diagnosis of achalasia but who have a shorter duration of symptoms, greater weight loss, and a more advanced age and who are referred for minimally invasive surgery should undergo additional imaging studies, including endoscopic ultrasound and computed tomography with fine cuts of the gastroesophageal junction, to rule out cancer.

Effort rupture of the oesophagus, or Boerhaave syndrome, is a spontaneous perforation of the oesophagus that results from a sudden increase in intraoesophageally pressure combined with negative intrathoracic pressure (e.g., severe straining or vomiting). The classic clinical presentation of Boerhaave syndrome usually consists of repeated episodes of retching and vomiting, typically in a middle-aged man with recent excessive dietary and alcohol intake.

These repeated episodes of retching and vomiting are followed by a sudden onset of severe chest pain in the lower thorax and the upper abdomen. The pain may radiate to the back or to the left shoulder. Swallowing often aggravates the pain.

Typically, hematemesis is not seen after oesophageal rupture, which helps to distinguish it from the more common Mallory-Weiss tear.

Swallowing may precipitate coughing because of the communication between the oesophagus and the pleural cavity. Shortness of breath is a common complaint and is due to pleuritic pain or pleural effusion.

A pulmonary embolism is a blood clot that occurs in the lungs.

It can damage part of the lung due to restricted blood flow, decrease oxygen levels in the blood, and affect other organs as well. Large or multiple blood clots can be fatal.
The most common symptom of a pulmonary embolism is shortness of breath. This may be gradual or sudden.

Other symptoms of a pulmonary embolism include:
anxiety
clammy or bluish skin
chest pain that may extend into your arm, jaw, neck, and shoulder
fainting
irregular heartbeat
light-headedness
rapid breathing
rapid heartbeat
restlessness
spitting up blood
weak pulse

Answer: It may result in metabolic complications such a refeeding syndrome, resulting in hyperkalaemia, hypermagnesemia, and hyperphosphatemia.

Refeeding syndrome can be defined as the potentially fatal shifts in fluids and electrolytes that may occur in malnourished patients receiving artificial refeeding (whether enterally or parenterally. These shifts result from hormonal and metabolic changes and may cause serious clinical complications. The hallmark biochemical feature of refeeding syndrome is hypophosphatemia. However, the syndrome is complex and may also feature abnormal sodium and fluid balance; changes in glucose, protein, and fat metabolism; thiamine deficiency; hypokalaemia; and hypomagnesaemia.
During refeeding, glycaemia leads to increased insulin and decreased secretion of glucagon. Insulin stimulates glycogen, fat, and protein synthesis. This process requires minerals such as phosphate and magnesium and cofactors such as thiamine. Insulin stimulates the absorption of potassium into the cells through the sodium-potassium ATPase symporter, which also transports glucose into the cells. Magnesium and phosphate are also taken up into the cells. Water follows by osmosis. These processes result in a decrease in the serum levels of phosphate, potassium, and magnesium, all of which are already depleted. The clinical features of the refeeding syndrome occur as a result of the functional deficits of these electrolytes and the rapid change in basal metabolic rate.

This patient is malnourished. Although surgery is imminent, it is best for him to be nutritionally optimised first. As he may have reduced surface area for absorption and has a localised perforation, total parenteral nutrition (TPN) is likely the best feeding modality.

The National Institute for Health and Care Excellence (NICE) has laid down guidelines for identifying patients as malnourished or at risk of malnourishment, in order to start oral, enteral, or parenteral nutrition support, alone or in combination.

Following patients are identified as malnourished:
1. BMI <18.5 kg/m2
2. Unintentional weight loss of >10% within the last 3–6 months
3. BMI <20 kg/m2 and unintentional weight loss of >5% within the last 3–6 months

Following patients are at risk of malnutrition:
1. Eaten nothing or little for >5 days and/or likely to eat little or nothing for the next 5 days or longer
2. Poor absorptive capacity and/or
3. High nutrient loss and/or
4. High metabolic rate

Considering the method of parenteral nutrition:
1. For feeding <14 days, consider feeding via a peripheral venous catheter
2. For feeding >30 days, use a tunnelled subclavian line,
continuous administration in severely unwell patients
3. If feed needed for >2 weeks, consider changing from continuous to cyclical feeding
4. Do not give >50% of daily regime to unwell patients in the first 24–48 hours
5. In surgical patients, if malnourished with unsafe swallow or a non-functional GI tract or perforation, consider perioperative parenteral feeding.

Patient-controlled analgesia (PCA) is a delivery system with which patients self-administer predetermined doses of analgesic medication to relieve their pain. The use of PCA in hospitals has been increasing because of its proven advantages over conventional intramuscular injections. These include improved pain relief, greater patient satisfaction, less sedation and fewer postoperative complications.

The combination of a high reticulocyte count and severe anaemia indicates aplastic crisis in patients with sickle cell anaemia. Another differential can be that of a transient aplastic crisis due to parvovirus. This is less likely as it causes reticulocytopenia rather than reticulocytosis.

Parvovirus B19 infects erythroid progenitor cells in the bone marrow and causes temporary cessation of red blood cell production. People who have underlying haematologic abnormalities such as sickle cell anaemia are at risk of cessation of red blood cell production if they become infected. This can result in a transient aplastic crisis. It is more common in people of African, Indian, and Middle Eastern backgrounds. Typically, these patients have a viral prodrome followed by anaemia, often with haemoglobin concentrations falling below 5.0 g/dL and reticulocytosis.

Colonic injuries that are managed with resection are associated with a high complication rate regardless of whether an anastomosis or colostomy is performed. Colonic resection and anastomosis can be performed safely in the majority of patients with severe colonic injury, including injuries to the left colon. For injuries of the right colon, an ileocolostomy has a lower incidence of leakage than a colocolonic anastomosis. For injuries to the left colon, there remains a role for colostomy specifically in the subgroups of patients with a high ATI or hypotension, because these patients are at greater risk for an anastomotic leak. The role of resection and primary anastomosis versus colostomy in colonic trauma requires further investigation.

In a surgical patient, hepatic dysfunction translates into an increased risk of infection, haemorrhage, thrombosis, and a prolonged half-life of numerous drugs (e.g., opioids and benzodiazepines). The associated imbalance of neuroendocrine mediators (e.g., vasopressin, renin-angiotensin-aldosterone system, and nitric oxide) also potentiates sodium and fluid retention, resulting in a background hyperdynamic circulation with splanchnic venous congestion and systemic vasodilation.
In emergency surgery, stress response to the underlying condition, anaesthesia, and surgical trauma increase the risk of hepatic decompensation and associated multi-system failure. Changes in hepatic perfusion with shock and fluid shifts further compromise hepatocellular synthetic and excretory functions. In addition, endotoxemia from gram-negative sepsis potentiates platelet aggregation and creates a state of low-grade disseminated intravascular coagulation.
Activation of the renin-angiotensin-aldosterone system with hypersecretion of vasopressin acts as compensatory mechanisms to preserve arterial pressure and replenish effective circulating volume when blood is pooled in the splanchnic territory. With the progression of cirrhosis, avidity for water and sodium increases, and dilutional hyponatremia results from water retention. In advanced cases, exacerbation of these abnormalities leads to hepatorenal syndrome (HRS). HRS is characterized by a rapid decline in renal function with low urinary excretion of sodium due to severe renal vasoconstriction and diminished or absent cortical perfusion. This syndrome is potentially reversible but carries an extremely poor prognosis.

Owing to raised intra-abdominal pressure due to ascites and muscle weakness from decreased muscle mass and malnutrition, umbilical and inguinal hernia incidence is higher in patients with cirrhosis.
If the patient with cirrhosis has umbilical hernia with obstructive symptoms such as intermittent incarceration or trophic skin changes, surgical repair should be considered.

Euvolemia and electrolyte homeostasis should be maintained under strict clinical and laboratory monitoring. Acute kidney injury in the absence of hemodynamic instability, use of nephrotoxic drugs, or parenchymal renal disease suggests the diagnosis of hepatorenal syndrome. Additional diagnostic criteria include no improvement in renal function after volume expansion with albumin and diuretic withdrawal. Treatment of hepatorenal syndrome requires the use of splanchnic vasoconstrictors (terlipressin, noradrenalin, or midodrine) and albumin infusion. Improved renal function has been demonstrated with medical treatment, but a mortality benefit is only ultimately achieved with liver transplantation. TIPS placement and renal and hepatic replacement therapies can be indicated as bridging strategies.

It has been well established that any delay in the resumption of normal oral diet after major surgery is associated with increased rates of infectious complications and delayed recovery. Early oral diet is safe 4 h after surgery in patients with a new non-diverted colorectal anastomosis. Some report that low residue diet, rather than a clear liquid diet, after colorectal surgery is associated with less nausea, faster return of bowel function, and a shorter hospital stay without increasing postoperative morbidity when administered in association with prevention of postoperative ileus. Spontaneous food intake rarely exceeds 1200–1500 kcal/day. To reach energy and protein requirements, additional oral nutritional supplements are useful.

One of the most serious post-ERCP complications is cholangitis leading to subsequent septicaemia. Enteric bacteria enter the biliary tree by the hematogenous route or following endoscopic or radiologic manipulation. Improperly disinfected endoscopes and accessories may also introduce infection into the biliary tree. The most common organisms responsible for infection after ERCP are the Enterobacteriaceae (especially Escherichia coli and Klebsiella species), alpha-haemolytic streptococci, Pseudomonas aeruginosa, Enterococcus, and Staphylococcus epidermidis. In most patients with acute cholangitis, a single organism is isolated from blood cultures.

Acute cholangitis is a clinical syndrome characterized by fever, jaundice, and abdominal pain that develops as a result of stasis and infection in the biliary tract. It is also referred to as Charcot’s Triad. Cholangitis was first described by Charcot as a serious and life-threatening illness; however, it is now recognized that the severity can range from mild to life-threatening.

Risk factors for post-ERCP infection include the use of combined percutaneous and endoscopic procedures, stent placement in malignant strictures, the presence of jaundice, low case volume, and incomplete or failed biliary drainage. Patients who are immunocompromised are more likely to experience an infectious complication.

Prevention and/or reduction of the risk of post-ERCP infectious complications can be achieved by judicious use of preprocedural antibiotics and intraprocedural steps, such as minimizing or avoiding contrast injection in patients with known biliary obstruction or cholangitis, endoscopic decompression, including the placement of a biliary stent when complete drainage cannot be achieved, and prompt percutaneous drainage if endoscopic drainage is not possible or incomplete. Prophylactic preprocedural antibiotics should be given to patients with jaundice and suspected mechanical obstruction. In addition, patients with sclerosing cholangitis, pancreatic pseudocysts, and those who are immunocompromised should also receive preprocedural antibiotics

Clostridioides difficile (formerly Clostridium difficile) colitis results from a disturbance of the normal bacterial flora of the colon, colonization by C difficile, and the release of toxins that cause mucosal inflammation and damage. Antibiotic therapy is the key factor that alters the colonic flora. C difficile infection (CDI) occurs primarily in hospitalized patients.
The diagnosis of C difficile colitis should be suspected in any patient with diarrhoea who has received antibiotics within the previous 3 months, has been recently hospitalized, and/or has an occurrence of diarrhoea within 48 hours or more after hospitalization. In addition, C difficile can be a cause of diarrhoea in community dwellers without previous hospitalization or antibiotic exposure

The following recommendations on Clostridium difficile infection (CDI) were released on February 2018 by the Infectious Diseases Society of America (ISDA) and Society for Healthcare Epidemiology of America (SHEA).
Diagnosis (adults)
Patients with unexplained and new-onset ≥3 unformed stools in 24 hours are the preferred target population for testing for CDI.
Use a stool toxin test as part of a multistep algorithm (i.e., glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT]; or NAAT plus toxin) rather than NAAT alone for all specimens when there are no pre-agreed institutional criteria for patient stool submission.
Use NAAT alone or a multistep algorithm for testing (i.e., GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than a toxin test alone when there are pre-agreed institutional criteria for patient stool submission.
Do not perform repeat testing (within 7 days) during the same episode of diarrhoea and do not test stool from asymptomatic patients, except for epidemiologic studies

Carcinoid syndrome occurs in ∼20% of cases of well-differentiated endocrine tumours of the jejunum or ileum (midgut neuroendocrine tumours (NET) and consists of (usually) dry flushing (without sweating; 70% of cases) with or without palpitations, diarrhoea (50% of cases) and intermittent abdominal pain (40% of cases); in some patients, there is also lacrimation and rhinorrhoea.
Carcinoid syndrome occurs less often with NETs of other origins and is very rare in association with rectal NETs. It is usually due to metastasis to the liver, with the release of vasoactive compounds, including biogenic amines (e.g., serotonin and tachykinins), into the systemic circulation. However, it may also occur in the absence of liver metastases if there is direct retroperitoneal involvement, with venous drainage bypassing the liver. Pain due to hepatic enlargement may also be a presenting feature, as may upper right abdominal pain (similar to that of pulmonary infarction) secondary to either haemorrhage into, or necrosis of, a hepatic secondary tumour. Wheezing and pellagra are less common presenting features. CHD is present in ∼20% of patients at presentation and usually indicates that the syndrome has been present for several years.

The aim of treatment should be curative where possible but it is palliative in the majority of cases.
Surgery is the only curative treatment.
Administration of specific medications to treat symptoms should, therefore, start as soon as clinical and biochemical signs indicate the presence of hypersecretory NETs, even before the precise localisation of primary and metastatic lesions is confirmed.

The only proven hormonal management of NETs is by the administration of somatostatin analogues.
Somatostatin analogues bind principally to SSTR subtypes 2 (with high affinity) and 5 (with lower affinity), thus inhibiting the release of various peptide hormones in the gut, pancreas and pituitary; they also antagonise growth factor effects on tumour cells, and, at very high dosage, may induce apoptosis. The effects of somatostatin analogues are demonstrable as biochemical response rates (inhibition of hormone production) in 30–70% of patients and as symptomatic control in the majority of patients.
There are two commercially available somatostatin analogues: octreotide and lanreotide.

Acute respiratory distress syndrome (ARDS) is an inflammatory process in the lungs that induces non-hydrostatic protein-rich pulmonary oedema. The immediate consequences are profound hypoxemia, decreased lung compliance, and increased intrapulmonary shunt and dead space. The clinicopathological aspects include severe inflammatory injury to the alveolar-capillary barrier, surfactant depletion, and loss of aerated lung tissue.

The most recent definition of ARDS, the Berlin definition, was proposed by a working group under the aegis of the European Society of Intensive Care Medicine. It defines ARDS by the presence within 7 days of a known clinical insult or new or worsening respiratory symptoms of a combination of acute hypoxemia (PaO2/FiO2 ≤ 300 mmHg), in a ventilated patient with a positive end-expiratory pressure (PEEP) of at least 5 cmH2O, and bilateral opacities not fully explained by heart failure or volume overload i.e. the heart pressure is norma. The Berlin definition uses the PaO2/FiO2 ratio to distinguish mild ARDS (200 < PaO2/FiO2 ≤ 300 mmHg), moderate ARDS (100 < PaO2/FiO2 ≤ 200 mmHg), and severe ARDS (PaO2/FiO2 ≤ 100 mmHg).
Most cases of ARDS in adults are associated with pulmonary sepsis (46 percent) or nonpulmonary sepsis (33 percent). Risk factors include those causing direct lung injury (e.g., pneumonia, inhalation injury, pulmonary contusion) and those causing indirect lung injury (e.g., nonpulmonary sepsis, burns, transfusion-related acute lung injury)

Most patients with ARDS need sedation, intubation, and ventilation while the underlying injury is treated. Any ventilator mode may be used, according to the Surviving Sepsis Clinical Practice Guideline and the National Heart, Lung, and Blood Institute’s ARDS Network (ARDSNet). Respiratory rate, expiratory time, positive end-expiratory pressure, and FiO2 are set following ARDSNet protocols. Settings are adjusted to maintain an oxygen saturation of 88 to 95 percent and a plateau pressure of 30 cm H2O or less to avoid barotrauma. Clinical practice guidelines recommend maintaining an arterial pH of 7.30 to 7.45, although patients in some research trials have tolerated permissive hypercapnia and a pH as low as 7.15