Abhinav Agrawal

Computational classification of mitochondrial shapes reflects stress and redox state

Dynamic variations in mitochondrial shape have been related to function. However, tools to automatically classify and enumerate mitochondrial shapes are lacking, as are systematic studies exploring the relationship of such shapes to mitochondrial stress. Here we show that during increased generation of mitochondrial reactive oxygen species (mtROS), mitochondria change their shape from tubular to donut or blob forms, which can be computationally quantified. Imaging of cells treated with rotenone or antimycin, showed time and dose-dependent conversion of tubular forms to donut-shaped mitochondria followed by appearance of blob forms. Time-lapse images showed reversible transitions from tubular to donut shapes and unidirectional transitions between donut and blob shapes. Blobs were the predominant sources of mtROS and appeared to be related to mitochondrial-calcium influx. Mitochondrial shape change could be prevented by either pretreatment with antioxidants like N-acetyl cysteine or inhibition of the mitochondrial calcium uniporter. This work represents a novel approach towards relating mitochondrial shape to function, through integration of cellular markers and a novel shape classification algorithm.

Euglycemic Diabetic Ketoacidosis: A Review

INTRODUCTION Diabetic ketoacidosis (DKA) is one of the most serious complications of diabetes. It is characterised by the triad of hyperglycemia (blood sugar >250 mg/dl), metabolic acidosis (arterial pH <7.3 and serum bicarbonate <18 mEq/L) and ketosis. Rarely these patients can present with blood glucose (BG) levels of less than 200 mg/dl, which is defined as euglycemic DKA. The possible etiology of euglycemic DKA includes the recent use of insulin, decreased caloric intake, heavy alcohol consumption, chronic liver disease and glycogen storage disorders. DKA in pregnancy has also been reported to present with euglycemia. The recent use of sodium glucose cotransporter 2 (SGLT2) inhibitors has shed light on another possible mechanism of euglycemic DKA. Clinicians may also be misled by the presence of pseudonormoglycemia. CONCLUSION Euglycemic DKA thus poses a challenge to physicians, as patients presenting with normal BG levels in ketoacidosis may be overlooked, leading to a delay in appropriate management strategies. In this article, we review all the possible etiologies and the associated pathophysiology of patients presenting with euglycemic DKA. We also discuss the approach to diagnosis and management of such patients. Despite euglycemia, ketoacidosis in diabetic patients remains a medical emergency and must be treated in a quick and appropriate manner.

Nivolumab causing painless thyroiditis in a patient with adenocarcinoma of the lung

Thyroiditis is characterised by transient hyperthyroidism, followed sometimes by hypothyroidism, and then recovery. We report a case of painless drug-induced thyroiditis—in a patient with no history of any thyroid disorder—treated with Nivolumab (an IgG4 monoclonal antibody against Programmed Death Receptor 1). The purpose of this case report is to increase awareness among clinicians regarding this possible adverse effect from Nivolumab, and discuss the possible pathophysiology and management strategies in such patients.

Post splenectomy related pulmonary hypertension

Splenectomy predisposes patients to a slew of infectious and non-infectious complications including pulmonary vascular disease. Patients are at increased risk for venous thromboembolic events due to various mechanisms that may lead to chronic thromboembolic pulmonary hypertension (CTEPH). The development of CTEPH and pulmonary vasculopathy after splenectomy involves complex pathophysiologic mechanisms, some of which remain unclear. This review attempts congregate the current evidence behind our understanding about the etio-pathogenesis of pulmonary vascular disease related to splenectomy and highlight the controversies that surround its management.

Pulmonary manifestations of renal cell carcinoma

Renal cell carcinoma (RCC) accounts for majority of all primary renal neoplasms. Classic manifestations of RCC include the triad of flank pain, hematuria and a palpable renal mass. Patients with RCC can develop various extra renal manifestations including involvements of the lungs, inferior vena cava, liver and the bones. The pulmonary manifestations of renal cell carcinoma include metastatic disease including endobronchial, pleural, parenchymal or lymph node metastasis, pleural effusion or hemothorax. Pulmonary embolism and tumor embolism is another common manifestation of renal cell carcinoma. RCC is a highly vascular tumor and can cause pulmonary arterio-venous fistulas leading to high output failure. Rarely, RCC can also present with paraneoplastic presentations including cough or bilateral diaphragm paralysis. Drugs used to treat RCC have been associated with drug related pneumonitis and form an important differential diagnosis in patients with RCC on therapy presenting with shortness of breath. In this review we discuss the various pulmonary manifestations of RCC. A high index of suspicion with these presentations can lead to an early diagnosis and assist in instituting an appropriate intervention.

Extracardiac manifestations of atrial myxomas

Primary cardiac tumors are extremely rare and constitute only about 5% of all cardiac tumors. Cardiac myxomas are noncancerous primary tumors of the heart and constitute about of 50% of all primary heart tumors. Left-sided atrial myxomas are more common than right-sided atrial myxomas. Atrial myxomas can lead to a triad of complications. The most common symptoms are associated with obstruction due to the size and location of the tumor. The next most common symptoms are associated with pulmonary and systemic embolization. Patients may also present with constitutional symptoms. Diagnosis is made via means of transesophageal echocardiography and magnetic resonance imaging. Early diagnosis and surgical resection remain the treatment of choice to prevent complications. Patients usually have a good prognosis after resection.

Cardiac manifestations of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, parenchymal disease of the lung with an estimated prevalence of 14-43 per 100,000. Patient usually presents with coughing and exertional dyspnea, which can lead to acute respiratory failure. IPF has been associated with various co-morbidities such as lung cancer, emphysema, obstructive sleep apnea (OSA), GERD and multiple cardiovascular consequences. The cardiovascular manifestations of IPF include pulmonary hypertension, heart failure, coronary artery disease, cardiac arrhythmias & cardiac manifestations of drugs used to treat IPF. This review will outline evidence of the association between IPF and cardiovascular conditions and attempt to provide insights into the underlying pathophysiology. We also discuss the impact of these cardiovascular diseases on patients with IPF including increased morbidity and mortality.

Rare adverse effect of a common drug: nitrofurantoin-induced ANCA-associated vasculitis

Nitrofurantoin is commonly prescribed to treat urinary tract infections (UTI). Reported adverse effects include gastrointestinal, pulmonary, hepatic and neurological disorders. We report a case of a 67-year-old woman treated for UTI with nitrofurantoin who presented with antineutrophilic cytoplasmic antibody (ANCA)-associated renal and skin vasculitis 3 days after starting treatment. The symptoms resolved following withdrawal of the drug and treatment with steroids. This is the first reported case of nitrofurantoin causing ANCA-associated vasculitis.

Nationwide trends in inpatient admissions of pulmonary hypertension in the United States from 2000 to 2013

INTRODUCTION Pulmonary hypertension (PH) is a disorder of the pulmonary vasculature with high mortality and bears a large economic burden on the healthcare system. We conducted a review of the largest inpatient database in the United States and analyzed the trends in hospitalizations due to PH from the turn of the century (2000) to 2013 to evaluate the rate of hospitalizations and determine the cost and mortality associated with PH. MATERIAL AND METHODS We analyzed the National Inpatient Sample Database (NIS) for all patients in which PH (Primary or Secondary) or cor pulmonale was the primary discharge diagnosis (ICD-9: 416.0, 416.8 and 416.9) from 2000 to 2013. The NIS is the largest all-payer inpatient database in the United States and contains data from approximately 8 million hospital stays each year. The statistical significance of the difference in the number of hospital discharges, lengths of stays and associated hospital costs over the study period was calculated. RESULTS In 2000, there were 12,066 hospital admissions with the principal discharge diagnosis of pulmonary hypertension, which increased to 13,605 admissions in 2013 (p < 0.001). The mean length of stay for PH increased from 5.89 days to 6.67 days during this period (p = 0.04). During the same period, the hospital charges increase by 174.5% from US

Endocarditis in left ventricular assist device

24,973 in 2000 to US