Sandbox:AyeshaFJ

Acute Respiratory Distress Syndrome

• The novel coronavirus was named as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to its high similarity to SARS-CoV, which caused acute respiratory distress syndrome (ARDS) in 2002–2003.
• SARS-CoV-2 virus primarily affects the respiratory system causing wide variety of respiratory symptoms which can range from symptoms of lower respiratory tract infection to severe hypoxia to acute respiratory distress syndrome within a very short span of time.

Epidemiology

• Incidence is higher in the elderly and much lower in children
• Higher mortality rate is seen in the elderly.

Pathophysiology

• ARDS arises as a complication of COVID-19 infection due to acute inflammation of the alveolar space which prevents normal gas exchange. The increase in proinflammatory cytokines within the lung leads to recruitment of leukocytes, further propagating the local inflammatory response
• The cytokine storm and the deadly uncontrolled systemic inflammatory response resulting from the release of large amounts of proinflammatory cytokines including interferons and interleukins and, chemokines by immune effector cells resulting in acute inflammation within the alveolar space. The exudate containing plasma proteins, including albumin, fibrinogen, proinflammatory cytokines and coagulation factors will increase alveolar-capillary permeability and decrease the normal gas exchange and plasma proteins, including albumin, fibrinogen, proinflammatory cytokines and coagulation factors.
• The COVID-19 patients with ARDS show elevated levels of IL-6, IFN-a, and CCL5, CXCL8, CXCL-10 in serum compared to those with the mild-moderate disease [11]
• This inflammatory process leads to the fibrin deposition in the air spaces and lung parenchyma and contributes to hyaline-membrane formation and subsequent alveolar fibrosis.
• Patients infected with COVID‐19 exhibit coagulation abnormalities. This procoagulant pattern can lead to acute respiratory distress syndrome.

Diagnosis

Laboratory findings

• Blood plasma has elevated levels of IL-6, IL-1, tumor necrosis factor-α (TNF α) and C-reactive protein.
• Mild thrombocytopenia
• Increased D-dimer levels. The elevated level of D-dimer is strongly associated with a higher mortality rate.
• Increased fibrin degradation products
• Increased fibrinogen.
• Prothrombin time and activated partial thromboplastin time may be slightly elevated.

Imaging studies

• Chest CT scan shows characteristic ground-glass opacities (GCO). This indicates the presence of exudate in the bronchoalveolar airspace.
• Lung biopsy shows fibrin deposition.

Signs and Symptoms

• Dyspnea: The onset of dyspnea is relatively late around the 6th day.
• Acute Hypoxemia due to respiratory failure is a dominant finding.
• Hypercapnea could be present but it is rare.

Treatment

Mechanical Ventilation

• Majority of COVID-19 patients with ARDS require mechanical ventilation for two weeks or more. The aim is to maintain oxygen saturation between 90 and 96%. The severe hypoxemia of the COVID-19 ARDS best responds when Positive end-expiratory pressure (PEEP) is high with Pplat ≤30 cm H2O. It is beneficial if the physician starts with higher than usual levels o PEEP (10 to 15 cm H2O).

Anticoagulant or thrombolytic therapy

• Fibrinolytic drugs such as tissue-type plasminogen activator (tPA) degrade pre-existing fibrin in the lungs.
• Nebulizer plasminogen activators may provide more targeted therapy to degrade fibrin and improving oxygenation in critically ill patients. It is in Phase II of the clinical trial.

Prevention

• The ARDS patients have an increased risk of hospital-associated venous thromboembolism (VTE). Due to this reason, it is advised to take low molecular weight heparin (LMWH) prophylactically in patients who do not have the contraindications. Studies have shown that the heparin, either unfractionated or LMWH, can also reduce inflammatory biomarkers hence could help in reducing the inflammation.

Cardiovascular Disorders and COVID-19

Out of hospital SCD

Pathophysiology

• Drug induced:

Since the COVID-19 pandemic, several pharmacological therapies have been proposed, one of them is of two anti-malarial and antirheumatic drugs called Chloroquine or Hydroxychloroquine. Due to their cost-effectiveness and easy availability, there is a surge in the use of Chloroquine and Hydroxychloroquine, with or without Azithromycin. The clinical trials in order to estimate their efficacy are still in the preliminary stage, however, a notable concern is of their cardiac adverse effects. This includes QT prolongation and Torsade de pointes (TdP) leading to sudden cardiac death. The risk is there when these drugs are prescribed separately, however it increases several folds when these drugs are administered together, especially in patients with underlying hepatic disease or renal failure.

• Genetic susceptibility:

Epidemiological studies have shown that African Americans have higher COVID-19 associated morbidity and mortality as compared to people from other ethnic groups. Recent studies show that this ethnic predilection is due to the genetics factors which contribute to a common ion channel variant p.Ser1103Tyr-SCN5A which confer an increased risk of drug-induced long QT syndrome (DI-LQTS) and drug-induced sudden cardiac death (DI-SCD). p.Ser1103Tyr-SCN5A generates late or persistent sodium current which is further aggravated by hypoxia or respiratory acidosis secondary to lungs involvement in COVID-19. This has and has been linked to an increased risk of ventricular arrhythmia (VA) such as torsade de pointes and sudden cardiac death (SCD) in African Americans

Spontaneous coronary dissection

Pathophysiology In patients with an inflammatory overload, a localized inflammation of the coronary adventitia and periadventitial fat can occur. This could lead to the development of sudden coronary artery dissection in a susceptible patient. Signs and symptoms Treatment

Neurofibromatosis

Neurofibromatosis 1

Neurofibromatosis 2

NF1 tumor suppresor gene Mutation located on chromosome 17, encodes for neurofibromin

NF2 tumor suppresor gene Mutation located on chromosome 22, encodes for merlin

clinical features: Cafe-au-lait spots, multiple neurofibromas and lisch nodules

Clinical features: bilateral acoustic neuromas

Features of Wenicke-Korsakoff Syndrome
Associated conditions	Chronic alcoholism (most common). Malnutrition.
Pathophysiology	Thiamine deficiency impairs ATP generation leading to neuronal dysfunction and death. It mostly has paraventricular lesions involving mammillary bodies and dorsomedial bodies.
Clinical findings	Confusion. Oculomotor dysfunction (horizontal nystagmus and bilateral abducens palsy) Postural and gait ataxia. Memory impairment (permanent).
Treatment	Intravenous thiamine. Administration of glucose before the thiamine can worsen the symptoms.

Acne vulgaris
Clinical features	Comedonal acne:Closed or open comedones on forehead, nose and chin. Inflammatory acne: Small, erythematous papules and pustules. Nodular acne: Large painful nodules; sinus tracts and scarring.
Pathogenesis	Hyperkeratinization and obstruction of the pilosebacous follicles. Sebaceous gland enlargement and increased sebum production. Metabolism of sebaceous lipids by Cutibacterium acnes and release of inflammatory fatty acid. Follicular inflammation and rupture,
Risk factors	i) Increased circulating androgen (e.g. PCOS, puberty) ii) Mechanical trauma/friction (excessive scrubbing, tight clothing) iii) Comedogenic oil based skin and hair products. iv) Excessive heat. v) Obesity

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Criteria for the diagnosis of SLE
Clinical features	Characteristics
1)Malar rash	Fixed erythema, flat or raised, sparing the nasolabial folds
2)Discoid rash	Erythematous raised patches with adherent keratotic scarring and follicular plugging.
3)Photosensitivity	Rash due to unusual reaction to sunlight.
4)Oral ulcer	Oral or nasopharyngeal ulcers, which may be painless.
5)Arthritis	Non-erosive arthritis, involving >2 peripheral joints.
6)Serositis	Pleuritis or pericarditis
7)Renal disorder	Persistent proteinura ( >0.5g/24hrs) or cellular casts (red cell, granular or tubular).
8)Neurological disorder	Seizure or psychosis, in the absence of provoking drugs or metabolic derangement.
9)Hematological disorder	Haemolytic anemia or leucopenia (<4 x109) or lymphopenia (<1x109) or thrombocytopenia (<100x109) in the absence of offending drugs.
10)Immunological	Abnormal titre of Anti-DNA antibodies or presence of Sm antigen or positive antiphospholipid antibodies.
11)Anti-nuclear Antibody (ANA)	Abnormal ANA titre measured by immunofluorescence
Diagnosis of SLE is made in an adult if 4 out of 11 features are present either serially or simultaneously.

• Erythematous raised patches with adherent keratotic scarring and follicular plugging.

Congenital anomalies of the urinary system

Kidneys

Renal pelvis

Ureter

Renal agenesis

Duplication of renal pelvis

Duplication of ureter

Renal ectopia

Congenital megaureter

Horseshoe kidney

Post-caval ureter

Unilateral fusion

Ureterocele

Congenital cystic kidney

Infantile polycystic kidney

Unlilateral Multicystic Kidney

Simple cyst of the kidney

Aberrant renal vessels

T

Mycosis fungoides

Stage IA-IIA

Stage IIA

Stage III

Stage IV

• Expectane policy • Topical steroides [IV-A] • nb-UVB[III,A] • PUVA [III-A] • Topical mechlorethamine [II,B] • Local RT [IV,A]

• Skin direct therapy(SDT) + local radiotherapy • ST[III+A] • (SDT+) retiods[III,B] • (SDT+) IFN a {III,B] • TSEBT [III,A]

• (SDT+) retinoides • (SDT+) IFNa • ECPI INFa +/- rtinoides • Low dose MTX • [IV-B]

• Gemcitabine • Liposomal doxorubicin • Brentuximab vedotin[II,B]

• (SDT+) retinoides [III,B] • (SDT+) IFNa [III,B] • Retinoides +IFN a [II,B] • TSEBT [IV,A]

• Gemcitabin [IV,B] • Liposomal doxorubicin [IV,B] • Brentuximabvedotin [II,B] • Combinatio Cht [Iv,B] • AlloSCT[V,C]

TSEBT[LV,B]

• Combination Cht [IV,B] • AlloSCT [V,C]