Alpha-1-antitrypsin (AAT) is a member of the serine proteinase inhibitor (serpin) family of proteins with a broad spectrum of biological functions including inhibition of proteases, immune modulatory functions, and the transport of hormones.

Perinatal transmission is the most common cause of Hepatitis B infection worldwide. Post-exposure prophylaxis should be provided, which consists of hepatitis B immune globulin and hepatitis B vaccine within 12 hours of birth. Without this, about 40% will develop chronic infection.

The first line treatment for ascites that is symptomatic is paracentesis. If it is not symptomatic, treatment could be with salt and fluid restriction as well as spironolactone. If spironolactone maximum dosage is reached, you can use furosemide additionally. Amiloride is not a diuretic that is recommended in this case.

Sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated.
Organic nitrates and nitric oxide (NO) donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO via increasing cGMP concentrations.

Carboxylation of factor II, VII, IX, X and protein C is affected by warfarin. Factor XII is not affected.

The major delayed problem with radiotherapy is the development of secondary cancers. This risk begins to appear ten years after therapy.

Initiation of allopurinol treatment during an attack can exacerbate and prolong the episode. Thus treatment should be delayed until the attack resolves.

Here, the patient seems to be intolerant to standard metformin. In such cases, modified-release preparations is considered as the most appropriate next step.
There is some evidence that these produce fewer gastrointestinal side-effects in patients intolerant of standard-release metformin.

Metformin is a biguanide and reduces blood glucose levels by decreasing the production of glucose in the liver, decreasing intestinal absorption and increasing insulin sensitivity.
Metformin decreases both the basal and postprandial blood glucose.
Other uses: In Polycystic Ovarian Syndrome (PCOS), Metformin decreases insulin levels, which then decreases luteinizing hormone and androgen levels. Thus acting to normalize the menstruation cycle.

Note:
Metformin is contraindicated in patients with severe renal dysfunction, which is defined as a glomerular filtration rate (GFR) less than 30 ml/min/1.732m2.
Metformin overdose has been associated with hypoglycaemia and lactic acidosis, for this reason, it has a black box warning for lactic acidosis.

The principal mechanism by which strontium inhibits osteoclast activity is by enhancing the secretion of osteoprotegerin (OPG) and by reducing the expression of the receptor activator of nuclear factor κB ligand (RANKL) in osteoblasts.

Osteoporosis is defined as low bone mineral density caused by altered bone microstructure ultimately predisposing patients to low-impact, fragility fractures.

Management:
Vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete
Alendronate is the first-line treatment. Around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate.
Strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates.
Other medications that are useful in the treatment of osteoporosis are denosumab, teriparatide, raloxifene, etc.

Most patients with psoriatic arthritis present with monoarthritis or asymmetric oligoarthritis. The most common form of the disease is the one involving a few joints of the peripheral skeleton with a distinct asymmetry of symptoms. Involvement of the smaller joints of the hands and feet, especially distal interphalangeal joints, seems to be a characteristic feature. Arthritis mutilans is a rare and severe complication of psoriatic arthritis.

Inclusion body myositis (IBM) is a progressive muscle disorder characterized by muscle inflammation, weakness, and atrophy (wasting). It is a type of inflammatory myopathy. IBM develops in adulthood, usually after age 50. The symptoms and rate of progression vary from person to person. The most common symptoms include progressive weakness of the legs, arms, fingers, and wrists. Some people also have weakness of the facial muscles (especially muscles controlling eye closure), or difficulty swallowing (dysphagia). Muscle cramping and pain are uncommon, but have been reported in some people. The underlying cause of IBM is poorly understood and likely involves the interaction of genetic, immune-related, and environmental factors. Some people may have a genetic predisposition to developing IBM, but the condition itself typically is not inherited. Elevated creatine kinase (CK) levels in the blood (at most ,10 times normal) are typical in IBM. Muscle biopsy may display several common findings including; inflammatory cells invading muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins.

J waves in an ECG is associated with hypothermia, hypercalcemia, the Brugada syndrome, and idiopathic ventricular fibrillation. The other responses are all associated with atrial myxoma

This case describes Zollinger-Ellison syndrome. It is characterized by refractory peptic ulcer disease, often multiple ulcers. This is typically caused by secretion of gastrin from a gastrinoma, a neuroendocrine tumour. The most common site of ulceration is the duodenum. A symptom of a pancreatic gastrinoma may be steatorrhea from hypersecretion of gastrin. Serum gastrin levels > 1000 and a pH < 2 are diagnostic of pancreatic gastrinoma. The secretin test is a test that can differentiate gastrinoma from other causes of high gastrin levels. Gastrin will rise after secretin injection if the patient has a gastrinoma.

This clinical scenario describes pernicious anaemia. Anti-intrinsic factor (IF) antibodies are most specific for pernicious anaemia. Antigastric parietal cell antibodies have a higher sensitivity but are less specific for pernicious anaemia. The other antibodies listed are not related to pernicious anaemia. Anti-TTG is seen with Celiac’s disease, anti-TPO is seen with thyroid disease, GAD is seen with type I diabetes, but this does not explain her anaemia.

The most common causes of a sudden painless loss of vision are:
– ischaemic optic neuropathy
– occlusion of central retinal vein or artery
– vitreous haemorrhage
– retinal detachment.
Central retinal artery occlusion is due to thromboembolism (from atherosclerosis) or arteritis (e.g. temporal arteritis). Features include afferent pupillary defects, and a ‘cherry red’ spot on a pale retina.

The most possible diagnosis is a pituitary tumour. Pituitary tumours compress the optic chiasm inferiorly and can cause visual field defects (bitemporal hemianopia or quadrantanopia). Temporal arteritis usually develops in older people and acute glaucoma usually requires a family history. Amaurosis fugax is classed as a stroke and usually leads to reversible unilateral vision loss. A subconjunctival haemorrhage does not typically produce the symptoms described.

Reactive arthritis, (formerly known as Reiter’s syndrome), is an autoimmune condition that occurs after a bacterial infection of the gastrointestinal or urinary tract. It is categorized as a seronegative spondylarthritis because of its association with HLA-B27. Reactive arthritis primarily affects young men and usually presents with musculoskeletal or extra‑articular symptoms. The characteristic triad consists of arthritis, conjunctivitis, and urethritis. The diagnosis is based on clinical features such as patient history and physical examination; there are no specific tests for reactive arthritis. Treatment is primarily symptomatic and consists of the administration of NSAIDs, as most patients recover spontaneously. extraarticular dermatologic manifestations include skin lesions of the glans resembling psoriasis (balanitis circinata); hyperkeratinisation of the palms and soles (keratoderma blenorrhagicum), oral ulcers. There usually is no rash and the diagnosis is unrelated to the presence of rheumatoid factor. This is a clinical diagnosis.

The chief presentation in Leishmaniasis is a non healing, ulcerated, painless and non pruritic plaque, which does not respond to oral antibiotics. It can be classified into cutaneous and visceral forms and is caused by the sand fly. It is more prevalent in the hilly areas. Fusobacterium causes a tropical ulcer which is painful and shallow, while Troanasomiasis causes sleeping sickness.

The empty boxes indicate that the patient has run out of his medication.
Chronic administration of high doses of glucocorticoids (GCs) (e.g., prednisone or prednisolone) and also other hormones such as oestrogens, progestins, androgens and growth hormone induce varying degrees of tolerance, resulting in a progressively decreased response to the effect of the drug, followed by dependence and rarely addiction.
The glucocorticoid withdrawal syndrome (GWS) has been considered a withdrawal reaction due to established physical dependence on supraphysiological GC levels.
The severity of GWS depends on the genetics and developmental history of the patient, on his environment, and on the phase and degree of dependence the patient has reached. Its management should include a temporary increase in the dose of GCs followed by gradual, slow tapering to a maintenance dose.

Glomerulosclerosis is the scarring and hardening of the glomeruli known as diabetic glomerulosclerosis occurring in long-standing diabetes.

Though a common community pathogen, Staphylococcus Aureas is found twice as frequently in pneumonias in hospitalized patients. It often attacks the elderly and patients with CF and arises as a co-infection with influenza viral pneumonia. The clinical course is characterized by high fevers, chills, a cough with purulent bloody sputum, and rapidly progressing dyspnoea. The gross pathology commonly reveals an acute bronchopneumonia pattern that may evolve into a necrotizing cavity with congested lungs and airways that contain a bloody fluid and thick mucoid secretions.

Inherited metabolic disorders are often characterized by the lack of an essential enzyme and are currently treated by dietary restriction and other strategies to replace the substrates or products of the missing enzyme. Patients with homocystinuria lack the enzyme cystathionine β-synthase (CBS), and many of these individuals do not respond to current treatment protocols.

In patients with acute renal tubular necrosis, infection in the form of gram-negative septicaemia is the most common cause of death, especially while the patient is awaiting spontaneous recovery of their renal function.

Tiotropium is a specific long-acting antimuscarinic agent indicated as maintenance therapy for patients with COPD (chronic obstructive pulmonary disease).
It should be used cautiously in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction.
The most frequently encountered adverse effects of tiotropium include pharyngitis, bronchitis, sinusitis, dry mouth, cough, and headaches. Paradoxical bronchospasm may also occur as a rare side-effect.
Dry mouth occurs in up to 14% of patients taking tiotropium, in keeping with its anticholinergic profile.
Rarer side-effects include tachycardia, blurred vision, urinary retention, and constipation.

Felty syndrome is a severe subtype of seropositive Rheumatoid arthritis. Clinical triad consists of arthritis, splenomegaly, and neutropenia (leads to an increased risk of recurrent bacterial infections). Other symptoms include skin ulcers of the lower limbs (indicating vasculitis), hepatomegaly, fever, and chest pain (indicating pleuritis or pericarditis). It is associated with increased risk of developing non-Hodgkin lymphoma.

Nice guidelines for lung reduction surgery:

FEV1 > 20% predicted
PaCO2 < 7.3 kPa
TLco > 20% predicted
Upper lobe predominant emphysema

This patient has pCO2 of 7.4 so she is unsuitable for referral for lung reduction surgery.

Given that he has diverticula in the clinical scenario combined with his presenting symptoms, it is likely that he has diverticular disease. A low fibre diet would support this diagnosis. Acute diverticulitis would require treatment with antibiotics. Depending on the severity (Hinchey classification) would determine if he needs oral or IV antibiotics, hospital admission or outpatient treatment. Sometimes abscesses or micro perforations occur, which typical require drainage and possibly surgical intervention. Diverticular disease is clearly a better answer than other possible answer choices, simply based on the symptoms presented in the prompt (and mention of low fibre).

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. The common terminal pathway consists of complement components C5–C9, and activation forms the anaphylatoxin C5a, a strong proinflammatory mediator, and the membrane attack complex (MAC), which creates pores in the bacterial cell wall (12). Deficiencies in these late complement components have been recognized as a cause of recurrent and familial meningococcal infections.

The incidence rate is the number of new cases per population at risk in a given time period. For example, if a population initially contains 1,000 non-diseased persons and 28 develop a condition over two years of observation, the incidence proportion is 28 cases per 1,000 persons per two years, i.e. 2.8% per two years.
Prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seat-belt use). It is derived by comparing the number of people found to have the condition with the total number of people studied, and is usually expressed as a fraction, as a percentage, or as the number of cases per 10,000 or 100,000 people.
Incidence should not be confused with prevalence, which is the proportion of cases in the population at a given time rather than rate of occurrence of new cases. Thus, incidence conveys information about the risk of contracting the disease, whereas prevalence indicates how widespread the disease is.

Vitamin A toxicity is a rare cause of papilledema. In this case, the patient is likely to have been taking retinoids for psoriasis.

Encephalitis does not usually present with papilledema. Brain abscess, brain tumour and hydrocephalus are all less likely with a normal CT head.