A novel metric-based approach of scoring early host immune response from oro-nasopharyngeal swabs predicts COVID-19 outcome.

Unpredictable fatal outcome of COVID-19 is attributed to dysregulated inflammation. Impaired early adaptive immune response leads to late-stage inflammatory outcome. The purpose of this study was to develop biomarkers for early detection of host immune impairment at first diagnosis from leftover RNA samples, which may in turn identify high risk patients. Leftover RNA samples of COVID-19 patients at first diagnosis were stored. Following prospective follow-up, the samples were shorted and categorized into outcome groups. Impaired adaptive T cell response (severity score) and Impaired IL-10 response (undetectable IL-10 in the presence of high expression of a representative interferon response gene) were determined by RT-PCR based assay. We demonstrate that a T cell response based 'severity score' comprising rational combination of Ct values of a target genes' signature can predict high risk noncomorbid potentially critical COVID-19 patients with a sensitivity of 91% (95% CI 58.7-99.8) and specificity of 92.6% (95% CI 75.7-99) (AUC:0.88). Although inclusion of comorbid patients reduced sensitivity to 77% (95% CI 54.6-92.2), the specificity was still 94% (95% CI 79.8-99.3) (AUC:0.82). The same for 'impaired IL-10 response' were little lower to predict high risk noncomorbid patients 64.2% (95% CI 35.1-87.2) and 82% (95% CI 65.5-93.2) respectively. Inclusion of comorbid patients drastically reduce sensitivity and specificity51.6% (95% CI 33.1-69.8) and 80.5% (95% CI 64.0-91.8) respectively. As best of our knowledge this is the first demonstration of a metric-based approach showing the 'severity score' as an indicator of early adoptive immune response, could be used as predictor of severe COVID-19 outcome at the time of first diagnosis using the same leftover swab RNA. The work flow could reduce expenditure and reporting time of the prognostic test for an earliest clinical decision ensuring possibility of early rational management.

Cardiac dysfunction in cirrhotic portal hypertension with or without ascites.

BACKGROUND: Alteration of cardiovascular functions in patients with liver cirrhosis has been described and it correlates with severity of hepatic failure. But cardiac functions by conventional 2-dimensional (2-D) echocardiography has limitations. The aim of the study was to evaluate cardiac systolic and diastolic functions in liver cirrhosis patients with or without ascites by tissue Doppler imaging and conventional 2-D- echocardiography. METHODS: A cross sectional case control study of sixty patients. Twenty subjects grouped as healthy controls, pre-ascitic cirrhosis and cirrhosis with ascites were enrolled. Cardiac evaluation was done by both conventional Doppler and tissue Doppler echocardiography. RESULTS: Cirrhosis with portal hypertension is associated with increased heart rate, ejection fraction and mean peak systolic velocity, while mean arterial pressure is decreased. All cardiac chamber dilation occurs and is mostly seen in the left atrium. Ratio of early diastolic annular velocity to peak early diastolic annular wave velocity (E/e') was the most significant marker for diastolic dysfunction. E/e' ratio was 7.76±0.40, 12.55±1.73 and 11.4±1.19 in healthy controls, pre ascitic cirrhosis and ascitic cirrhosis respectively (P<0.0001). Overall Type I and II Left ventricular diastolic dysfunction was present in 70% cirrhotic patient with or without ascites, while there were no cases of Type III (Severe) diastolic dysfunction. CONCLUSION: Left ventricular diastolic dysfunction is commonly associated with advancement of hepatic dysfunction while systolic function is maintained till advanced hepatic failure. Peak early diastolic wave velocity, deceleration time and E/e' ratio for left ventricular diastolic dysfunction are accurately assessed by pulsed tissue Doppler imaging.

Neglected femoral diaphyseal fracture.

Femoral diaphyseal fractures usually result after trauma of high magnitude and because of this, can be life-threatening injuries or may result in considerable physical disability if not treated with care and caution. Nonoperative treatment of these fractures continues to be popular among the patient population in the Indian subcontinent, which in majority of cases, leads to healing in malalignment, shortening of the limb, chondromalacia patellae, and loss of knee motion. Although the majority of these fractures are being treated by operative methods today, success of the treatment depends largely on the surgeon's familiarity with the procedure or the type of fracture pattern (comminuted or segmental) particularly in a polytraumatized patient. Delayed union and nonunion of femoral-diaphyseal fractures and implant failures usually result after these procedures or the type of injury. The purpose of this study is to discuss various types of neglected femoral diaphyseal fractures and to review the literature on their treatment.