The most likely diagnosis is chronic tophaceous gout, which is classically associated with chronic renal impairment or long term diuretic therapy. There is tophus formation due to urate crystal deposition in and around the joint. These tophi can also form in the bones and soft tissues. Renal manifestations with uric acid include nephrolithiasis and uric acid nephropathy. Whenever there is an acute on chronic attack of gout, the inciting cause must be established and in case of diuretic use, they should be immediately replaced with another medication. Allopurinol is never started during an acute episode. it is first allowed to settle before administration of allopurinol. Although dietary restriction must be observed in people with a propensity of gout, this scenario clearly presents diuretics as the cause.

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.

Hepatitis B full vaccine and Ig should be given to babies born to hepatitis B positive mothers. Hepatitis B vaccine alone or Ig alone is not sufficient to prevent the infection in the new-born baby.

Type I interferons (IFNs) form a network of homologous cytokines that bind to a shared, heterodimeric cell surface receptor and engage signalling pathways that activate innate and adaptive immune responses.

Hyperchylomicronaemia is an increase (markedly) in chylomicrons, and this can cause acute pancreatitis, as well as xanthomas. It can be seen in familial lipoprotein lipase (LPL) deficiency, primary type V hyperlipoproteinemia, idiopathic hyperchylomicronaemia, and familial apolipoprotein CII deficiency. Treatment is dietary fat restriction in order to avoid pancreatitis attacks.

Relative risk reduction (RRR) tells you by how much the treatment reduced the risk of bad outcomes relative to the control group who did not have the treatment. In the previous example, the relative risk reduction of fever and rash in the group of the children on the intervention was 40 per cent (1 – 0.6 = 0.4 or 40 per cent). RRR = (EER -CER) / CER = (0.1 – 0.4) / 0.4 = -0.75 or 75% reduction.

All of the aforementioned options may be important however cytogenetics, for detecting chromosomal abnormalities, is the single most important test to determine her disease prognosis.

Acute myeloid leukaemia (AML) is the acute expansion of the myeloid stem line, which may occur as a primary disease or follow the secondary transformation of a myeloproliferative disorder. It is more common over the age of 45 and is characterized by signs and symptoms largely related to bone marrow failure such as anaemia (pallor, lethargy), frequent infections due to neutropenia (although the total leucocyte count may be very high), thrombocytopaenia (bleeding), ostealgia, and splenomegaly.

The disease has a poor prognosis if:
1. Age of the patient >60 years
2. >20% blasts seen after the first course of chemotherapy
3. Chromosomal aberration with deletion of part of chromosome 5 or 7.

Acute promyelocytic leukaemia (APL) is an aggressive form of AML.

Troponin T is a 37 ku protein that binds to tropomyosin, thereby attaching the troponin complex to the thin filament.

Anti-Sm antibodies are essential for diagnosis of SLE, especially in anti-dsDNA-negative patients. ANA are also found in 95% of the patients with SLE but they may also occur with other conditions like Juvenile inflammatory arthritis, chronic activity hepatitis, and Sjogren’s syndrome. Anti-Ro, although also found with SLE are more characteristic of Sjogren Syndrome. RF is usually associated with rheumatoid arthritis and cANCA with Wegener’s granulomatosis, Churg Strauss, and microscopic polyangiitis.

Cephalosporins, such as ceftriaxone, do not cover methicillin-resistant staph aureus. They do cover some gram positives and gram negatives. Vancomycin and teicoplanin given intravenously have good coverage of MRSA and other gram positive bacteria. Rifampicin and doxycycline, although not the best treatment, can be used for outpatients if there are no systemic signs of illness.

CURB Pneumonia Severity Score estimates the mortality of community-acquired pneumonia to help determine inpatient vs. outpatient treatment.
Select Criteria:
Confusion (abbreviated Mental Test Score <=8) (1 point)
Urea (BUN > 19 mg/dL or 7 mmol/L) (1 point)
Respiratory Rate > 30 per minute (1 point)
Blood Pressure: diastolic < 60 or systolic < 90 mmHg (1 point) The CURB-65 scores range from 0 to 5. Clinical management decisions can be made based on the score:
Score Risk Disposition
0 or 1 – 1.5% mortality – Outpatient care
2 – 9.2% mortality – Inpatient vs. observation admission
≥ 3 – 22% mortality – Inpatient admission with consideration for ICU admission with score of 4 or 5

Hashimoto thyroiditis is the most common cause of hypothyroidism in developed countries. In contrast, worldwide, the most common cause of hypothyroidism is an inadequate dietary intake of iodine. This disease is also known as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis.

Liver cirrhosis is not associated with hyposplenism.

Hyposplenism is caused by a variety of conditions. These are:
1. Splenectomy
2. Sickle cell anaemia
3. Coeliac disease, dermatitis herpetiformis
4. Graves’ disease
5. Systemic lupus erythematosus (SLE)

Giardiasis also known as travellers diarrhoea is caused by Giardia lamblia, which is an anaerobic parasite affecting the small intestine. It can lead to diarrhoea, flatulence, abdominal cramps, malodourous greasy stools and intestinal malabsorption. It can also cause bloody diarrhoea. The investigation of choice is stool examination for trophozoites and cysts. It is treated by metronidazole and tinidazole as first line therapies.

This is a classic clinical presentation, with alcohol intake and nausea/vomiting that leads to hematemesis, of a Mallory-Weiss tear. In Mallory-Weiss tear, they typically present as a hemodynamically stable patient after a night of binge drinking and excessive resultant vomiting. Given his EGD did not show any other pathology and he is now stable, he can be discharged home.

CMV infection is usually asymptomatic in adults. However, if the mother is infected for the first time during pregnancy then there is high chances of this infection passing on to the foetus. CMV infection can cause blindness, deafness, learning difficulties, restricted growth etc. Hepatitis B, herpes simplex, syphilis and HIV do not present with these classical signs of CMV infection in new-borns. It is estimated that 10 stillbirths occur in England and Wales every year due to CMV infection. The foetus is most at risk in early pregnancy. There is no effective prevention.

Positive predictive value is the probability that subjects with a positive screening test truly have the disease.

Positive predictive value = true positive / ( true positive + false positive)

Lysosomal hydrolases are synthesized in the rough endoplasmic reticulum and specifically transported through the Golgi apparatus to the trans-Golgi network, from which transport vesicles bud to deliver them to the endosomal/lysosomal compartment. The explanation of how the lysosomal enzymes are accurately recognized and selected over many other proteins in the trans-Golgi network relies on them being tagged with a unique marker: the mannose-6-phosphate (M6P) group, which is added exclusively to the N-linked oligosaccharides of lysosomal soluble hydrolases, as they pass through the cis-Golgi network. Generation of the M6P recognition marker depends on a reaction involving two different enzymes: UDP-N-acetylglucosamine 1-phosphotransferase and α-N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase.

Involvement of lymph nodes on both sides of the diaphragm accompanied by night sweats would be staged as IIIB according to the Ann Arbor staging system for Hodgkin lymphoma (HL).

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

Staging of HL is done according to the Ann Arbor staging system:
Stage
I: Single lymph node region (I) or one extra lymphatic site (IE)

II: Two or more lymph node regions on same side of the diaphragm (II) or local extra lymphatic extension plus one or more lymph node regions on same side of the diaphragm (IIE)

III: Lymph node regions on both sides of the diaphragm (III) which may be accompanied by local extra lymphatic extension (IIIE)

IV: Diffuse involvement of one or more extra lymphatic organs or sites

Suffix
A: No B symptoms

B: Presence of at least one of the following: unexplained weight loss >10% baseline during 6 months before staging; recurrent unexplained fever >38°C; recurrent night sweats—poor prognosis.

Given that the patient has had large amount, high volume watery diarrhoea in an acute period of time, from the answer choices given, this narrows the diagnosis down to VIPoma or carcinoid syndrome. You would expect with carcinoid syndrome for there to be periodic episodes of diarrhoea, though, with a description of flushing, additionally, associated with these episodes. Thus, VIPoma is the most likely answer here. VIPomas are known to cause hypokalaemia from this large amount of watery diarrhoea. Stool volume should be > 700 ml/day.

Osteopenia is an early sign of bone weakening that is less severe than osteoporosis.
The numerical result of the bone density test is quantified as a T score. The lower the T score, the lower the bone density. T scores greater than -1.0 are considered normal and indicate healthy bone. T scores between -1.0 and -2.5 indicate osteopenia. T scores lower than -2.5 indicate osteoporosis.
DEXA also provides the patient’s Z-score, which reflects a value compared with that of person matched for age and sex.
Z-score values of –2.0 SD or lower are defined as below the expected range for age and those above –2.0 SD as within the expected range for age.

Acute dacryocystitis presents as inflammation of the lacrimal sac and is typically caused by infection. Symptoms of acute dacryocystitis can be pain, redness of the eye and swelling of the nasal aspect of the eye. The eye is usually watery and discharge can be expressed through the lacrimal punctum which is generally mucoid but can also be purulent. Patient can also present with fever.

An odds ratio (OR) is a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions). Where

a = Number of exposed cases

b = Number of exposed non-cases

c = Number of unexposed cases

d = Number of unexposed non-cases

OR=(a/c) / (b/d) = ad/bc

Mild deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase activity may present in adolescence or adulthood with oligomenorrhea, hirsutism, and/or infertility. This is termed nonclassical adrenal hyperplasia.
Late-onset or nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Reported prevalence ranges from 1 in 30 to 1 in 1000. Affected individuals typically present due to signs and symptoms of androgen excess.
Treatment needs to be directed toward the symptoms. Goals of treatment include normal linear growth velocity, a normal rate of skeletal maturation, ‘on-time’ puberty, regular menstrual cycles, prevention of or limited progression of hirsutism and acne, and fertility. Treatment needs to be individualized and should not be initiated merely to decrease abnormally elevated hormone concentrations.
Normal Ultrasound rules out Turner’s syndrome.

1mg Prednisolone = 4mg hydrocortisone, so the actual equivalent daily dose is 7mg.

A typical attack may last less than an hour but can also persist for longer. In primary Raynaud’s, attacks are more likely symmetric, episodic, and without evidence of peripheral vascular disease. Patients more commonly have a negative ANA and normal inflammatory markers. There should be no evidence of tissue gangrene, digital pitting, or tissue injury in primary Raynaud’s. In contrast, patients with secondary Raynaud’s will describe attacks that are more frequent, painful, often asymmetric and may lead to digital ulcerations.

Northern blotting’s purpose is to measure the size and amount of RNA transcribed from a specific gene of interest.

Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors.
The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

From the given history the patient has NYHA grade III heart failure. He can be safely started on an ACE inhibitor as his serum potassium was towards the lower limit. As there an impairment of renal function, his urea, creatinine and serum electrolytes should be closely monitored after commencing an ACE inhibitor. Adding atenolol will not have any clinical benefit. Increasing the digoxin dose is not needed as the patient is in sinus rhythm. Increasing furosemide will only have symptomatic relief.

The walls of the ascending limb of the loop of Henle are not permeable to water. The tubular fluid thus becomes increasingly dilute as it ascends toward the cortex, whereas the interstitial fluid around the loops of Henle in the medulla becomes increasingly more concentrated.

The ascending limb actively reabsorbs NaCl but has an extremely low transepithelial osmotic water permeability, even in the presence of vasopressin. This combination of NaCl reabsorption without water reabsorption serves two vital functions: it provides NaCl to increase the osmolality of the medullary interstitium, tubules, vasculature, and collecting ducts; and it dilutes the luminal fluid within the thick ascending limb.