Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with the development of the following classic tumours: soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumours, adrenocortical carcinoma (ACC), and leukaemia. LFS is diagnosed in individuals meeting established clinical criteria or in those who have a germline pathogenic variant in TP53 regardless of family cancer history.

To differentiate ventricular tachycardia (VT) from supraventricular tachycardia (SVT) with aberrant conduction the following electrocardiographic features should be looked for:

Evidence of preceding atrial activity for SVT. Oesophageal leads are helpful if P waves are hidden in the QRS complex.
QRS duration more than 140 ms for VT.
QRS morphology: Features of QRS morphology that favour SVT are RBBB or triphasic patterns like rSR in V1 and qRS in V6. Monophasic pattern like R or qR in V1 and rS or QS in V6 or multiple morphology QRS complexes favour VT.
AV dissociation for VT.

This patient is most likely suffering from hand, foot mouth disease which is caused by coxsackie virus A16. Its incubation period ranges from 5-7 days and only symptomatic treatment is required.

Features that affect prognosis are tumour thickness in millimetres (Breslow’s depth – the deeper the Breslow thickness the poorer the prognosis.), depth related to skin structures (Clark level – the level of invasion through the dermis), type of melanoma, presence of ulceration, presence of lymphatic/perineural invasion, presence of tumour-infiltrating lymphocytes (if present, prognosis is better), location of lesion, presence of satellite lesions, and presence of regional or distant metastasis. Malignant melanoma tends to grow radially before entering a vertical growth phase. The diameter it reaches has not been found to be a prognostic factor.

Risk factors specific to depression:
-Family history of mental disorder.
-History of previous suicide attempts (this includes self-harm).
-Severe depression.
-Anxiety.
-Feelings of hopelessness.
-Personality disorder.
-Alcohol abuse and/or drug abuse.
-Male gender.

Protective Factors for Suicide.
Protective factors buffer individuals from suicidal thoughts and behaviour. To date, protective factors have not been studied as extensively or rigorously as risk factors. Identifying and understanding protective factors are, however, equally as important as researching risk factors.

Protective Factors:
-Effective clinical care for mental, physical, and substance abuse disorders
-Easy access to a variety of clinical interventions and support for help seeking
-Family and community support (connectedness)
-Support from ongoing medical and mental health care relationships
-Skills in problem solving, conflict resolution, and nonviolent ways of handling disputes
-Cultural and religious beliefs that discourage suicide and support instincts for self-preservation

The question describes an alcohol abusing man with chronic epigastric discomfort, radiating into his back, worse with meals, and foul-smelling stools, weight loss, as well as chronic nausea. This is likely, thus chronic pancreatitis due to alcohol abuse. Hepatomegaly and peripheral neuropathy secondary to anaemia support the diagnosis of long term alcohol abuse. Bacterial overgrowth may present with diarrhoea and is a less likely diagnosis than pancreatitis. Celiac disease is a less likely diagnosis than pancreatitis, and you would also expect mention of diarrhoea. VIPoma would also likely present with diarrhoea. Cecal carcinoma would more than likely present with blood in the stool.

Small cell lung cancer (SCLC) is characterized by rapid growth and early dissemination. Prompt initiation of treatment is important.

Patients with clinical stage Ia (T1N0) after standard staging evaluation may be considered for surgical resection, but combined treatment with chemotherapy and radiation therapy is the standard of care. Radiation therapy is often added at the second cycle of chemotherapy.

Historically, patients undergoing surgery for small cell lung cancer (SCLC) had a dismal prognosis. However, more recent data suggest that patients with true stage I SCLC may benefit from surgical resection.

Common sites of hematogenous metastases include the brain, bones, liver, adrenal glands, and bone marrow. The symptoms depend upon the site of spread.

The two statements that fit the characteristics of doxapram are, epilepsy is a contraindication for doxapram use and concurrent use with theophylline may increase agitation.

Doxapram is a central respiratory stimulant. In clinical practice, doxapram is usually used for patients who have an acute exacerbation of chronic obstructive pulmonary disease (COPD) who are unsuitable for admission to the intensive therapy unit for ventilatory support. Doxapram infusion may buy an extra 24 h to allow for recovery.

Contraindications include: ischaemic heart disease, epilepsy, cerebral oedema, acute stroke, asthma, hypertension, hyperthyroidism, and pheochromocytoma.
The infusion may worsen agitation and dyspnoea and lead to hypertension, nausea, vomiting and urinary retention.

Drug interactions:
Concomitant administration of doxapram and aminophylline (theophylline) can cause increased skeletal muscle activity, agitation, and hyperactivity.

The prognosis of breast cancer depends chiefly on the extent of nodal metastases.

The breast cancer TNM staging system is the most common way that doctors use to stage breast cancer. TNM stands for Tumour, Node, Metastasis. The results are combined to determine the stage of cancer for each person. There are five stages: stage 0 (zero), which is non-invasive ductal carcinoma in situ (DCIS), and stages I through IV (1 through 4), which are used for invasive breast cancer.

Staging can be clinical or pathological. Clinical staging is based on the results of tests done before surgery, which may include physical examinations, mammogram, ultrasound, and MRI scans. Pathologic staging is based on what is found during surgery to remove breast tissue and lymph nodes. In general, pathological staging provides the most information to determine a patient’s prognosis.

Post-traumatic stress disorder (PTSD) is an anxiety disorder caused by stressful, frightening or distressing events.

PTSD is a lasting consequence of traumatic ordeals that cause intense fear, helplessness, or horror, such as a sexual or physical assault, the unexpected death of a loved one, an accident, war, or natural disaster. Families of victims can also develop PTSD, as can emergency personnel and rescue workers.

PTSD is diagnosed after a person experiences symptoms for at least one month following a traumatic event. However symptoms may not appear until several months or even years later. The disorder is characterized by three main types of symptoms:
-Re-experiencing the trauma through intrusive distressing recollections of the event, flashbacks, and nightmares.
-Emotional numbness and avoidance of places, people, and activities that are reminders of the trauma.
-Increased arousal such as difficulty sleeping and concentrating, feeling jumpy, and being easily irritated and angered.

The goal of PTSD treatment is to reduce the emotional and physical symptoms, to improve daily functioning, and to help the person better cope with the event that triggered the disorder. Treatment for PTSD may involve psychotherapy (a type of counselling), medication, or both.

Certain antidepressant medications are used to treat PTSD and to control the feelings of anxiety and its associated symptoms including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants. Mood stabilizers such are sometimes used.

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

Based on the given clinical scenario, the most probable diagnosis in this patient is acute paranoid schizophrenia.

Schizophrenia is a functional psychotic disorder characterized by the presence of delusional beliefs, hallucinations, and disturbances in thought, perception, and behaviour.

Clinical features:
Schneider’s first-rank symptoms may be divided into auditory hallucinations, thought disorders, passivity phenomena, and delusional perceptions:

Auditory hallucinations of a specific type:
Two or more voices discussing the patient in the third person
Thought echo
Voices commenting on the patient’s behaviour

Thought disorder:
Thought insertion
Thought withdrawal
Thought broadcasting

Passivity phenomena:
Bodily sensations being controlled by external influence
Actions/impulses/feelings – experiences which are imposed on the Individual or influenced by others

Other features of schizophrenia include
Impaired insight (a feature of all psychoses)
Incongruity/blunting of affect (inappropriate emotion for circumstances)
Decreased speech
Neologisms: made-up words
Catatonia
Negative symptoms: incongruity/blunting of affect, anhedonia (inability to derive pleasure), alogia (poverty of speech), avolition (poor motivation).

Treatment:
For the initial treatment of acute psychosis, it is recommended to commence an oral second-generation antipsychotics such as aripiprazole, olanzapine, risperidone, quetiapine, etc.
Once the acute phase is controlled, switching to a depot preparation like aripiprazole, paliperidone, zuclopenthixol, fluphenazine, haloperidol, pipotiazine, or risperidone is recommended.
Cognitive-behavioural therapy (CBT) and the use of art and drama therapies help counteract the negative symptoms of the disease, improve insight, and assist relapse prevention.
Clozapine is used in case of treatment resistance.

Diseases that cause predominantly sensory loss include diabetes, uraemia, leprosy, alcoholism, vitamin B12 deficiency, and amyloidosis.
Those that cause predominantly motor loss include Guillain-Barre syndrome, porphyria, lead poisoning, hereditary sensorimotor neuropathies, chronic inflammatory demyelinating polyneuropathy, and diphtheria.

The patient is most likely to have Addison’s disease as he has a history of autoimmune disease, hyperkalaemia and hypotension.
It is important to keep an Addisonian crisis on the differential in cases of shock, especially since adrenal crisis can be the patient’s first presentation of adrenal insufficiency.
Patients with Addison’s disease are prone to developing hypoglycaemia due to loss of the glucogenic effect of glucocorticoids. Given the sudden deterioration, a glucose level must be checked.

Sitagliptin-induced pancreatitis can occur at any time after the initiation of therapy, even after several years. Patients taking sitagliptin who present with signs and symptoms of mild or severe pancreatitis should immediately discontinue sitagliptin and use an alternate medication regimen for control of type 2 diabetes.
In response to pancreatitis reported in post-marketing surveillance through the Adverse Event Reporting System (AERS), the FDA has issued revised prescribing information for sitagliptin stating that cases of acute pancreatitis have been reported with use, to monitor closely for signs and symptoms of pancreatitis, and to use sitagliptin with caution in patients with a history of pancreatitis.

Stricturing is associated with Crohn’s disease, and elevated CRP supports this diagnosis in this patient, as well. Infliximab should not yet be started. Acute treatment is steroids (of a flare) however this man needs surgery. Although surgery should be avoided if at all possible in Crohn’s disease, and minimal surgery should occur (resecting as little as possible, given possible need for future resections), including possible stricturoplasty instead of resection. Chronic pancreatitis is unlikely given it would not cause stricture. Patients undergoing surgery should always have informed consent, which always includes risk of a stoma for any bowel surgery. Given the amount of weight he has lost he is at significant risk for refeeding syndrome, which can cause hypokalaemia, hypophosphatemia and hypomagnesemia.

After renal transplantation, cytomegalovirus has been identified to affect 1/4 of the post-op patients. It is the most common viral infection causing morbidity and mortality in post-op patients in the first 3 months.

The patient seems to be conscious about his decision, which should be respected. According to Mental Capacity Act 2005, a person who makes an unwise decision should not be treated as unable to make a decision.

Urticaria is a group of disorders that share a distinct skin reaction pattern, namely the occurrence of itchy wheals anywhere on the skin. Wheals are short-lived elevated erythematous lesions ranging from a few millimetres to several centimetres in diameter and can become confluent. The itching can be prickling or burning and is usually worse in the evening or night time. Triggering of urticaria by infections has been discussed for many years but the exact role and pathogenesis of mast cell activation by infectious processes is unclear.

In myasthenia gravis, repeated muscle contractions lead to reduced muscle strength. The opposite is however classically seen in the related disorder Lambert-Eaton syndrome. Lambert-Eaton myasthenic syndrome is seen in association with small cell lung cancer, and to a lesser extent breast and ovarian cancer. It may also occur independently as an autoimmune disorder. Lambert-Eaton myasthenic syndrome is caused by an antibody directed against pre-synaptic voltage gated calcium channel in the peripheral nervous system.

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.

Weber’s test – if there is a sensorineural problem, the sound is localized to the unaffected side (right), indicating a problem on the left side.

Huntington’s disease is an autosomal inherited condition characterized by progressive dementia and worsening choreiform movements. Symptoms typically appear between ages 30 and 50. Ultimately the weakened individual succumbs to pneumonia, heart failure, or other complications.

Renal biopsy in this patient will most likely show thickened glomerular basement membrane with deposits of IgG and C3 as a result of membranous glomerulonephritis that has caused the nephrotic syndrome in this patient. Membranous glomerulonephritis in this case is most likely associated with an underlying bronchial carcinoma, consistent with the patient’s smoking history and physical presentation.

The pons is above the level of decussation of the corticospinal tracts so a pontine lesion would cause a contralateral limb weakness.
The facial motor nucleus is located in the pons and supplies the ipsilateral facial muscles.
A right cerebral lesion would give left upper and lower limb weakness. It would also cause a left sided facial weakness.
A left cerebral lesion would give right upper and lower limb weakness with right facial weakness.
Finally, a cervical spinal cord lesion would not cause a facial weakness.

Warfarin inhibits the vitamin K-dependent procoagulants II, VII, IX, and X as well as anticoagulant protein C and S. It is highly protein-bound and can be displaced by a wide variety of drugs. It has a half-life of 36–48 hours.

Bleeding is the major side effect. Easy bruising, as seen in this case, is commonly seen in patients of warfarin overdose. Grossly prolonged PT and lesser increase in APTT may be seen in such cases.

Live virus vaccines include: Vaccinia (smallpox), Measles, Mumps, Rubella (MMR combined vaccine), Varicella (chickenpox), Influenza (nasal spray), Rotavirus, Zoster (shingles) and Yellow fever. Inactivated vaccines are Polio (IPV), Hepatitis A and Rabies.

This patient is having a myasthenic crisis. Opinions vary as to whether plasmapheresis or intravenous immunoglobulins should be given first-line. Plasmapheresis usually works much faster, but is more costly due to equipment.
Myasthenia gravis is an autoimmune disorder resulting in insufficient functioning acetylcholine receptors. Antibodies to acetylcholine receptors are seen in 85-90% of cases. Myasthenia gravis is more common in women (2:1).

Normal pressure hydrocephalus is a form of communicating hydrocephalus characterised by enlarged ventricles with normal opening pressure on lumbar puncture. For diagnostic purposes, a triad of urinary incontinence, gait abnormality and dementia is necessary. It is necessary to diagnose the condition early because it is reversible by placing a ventriculoperitoneal shunt. It is most common in patients aged more than 60 years.

Night sweats are a B symptom in Hodgkin lymphoma (HL) and imply a poor prognosis.

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.