Background Hydroxychloroquine is being administered among patients with COVID19 infection in many healthcare systems across the world considering its in vitro effect against the SARS CoV 2 virus. In spite of several observational studies and a few randomized controlled trials, the effect of hydroxychloroquine on patients with COVID 19 infection remains unclear. We undertook this systematic review with meta-analysis to evaluate the efficacy and safety of hydroxychloroquine among patients with COVID 19 infection. Methods We searched PubMed, Embase, the Cochrane Library, Web of Science, medRxiv, and other relevant resources until May 13, 2020. We included randomized controlled trials and observational studies in which hydroxychloroquine was adminstered and compared to a control group. Data were extracted, and quality assessment of the studies was carried out. We evaluated symptomatic progression, mortality, viral clearance, the evolution of changes on chest CT imaging, and adverse events. A fixed or random-effects model was used depending on outcome heterogeneity. Results We included eleven studies including, three randomized controlled trials and eight observational studies. Among these, 2354 patients received hydroxychloroquine alone or in combination, while 1952 did not. Mortality was reported at different points of time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 1.41, 95% CI: 0.76 to 2.62; p = 0.28). Clinical worsening or lack of symptomatic improvement did not differ between patients who received hydroxychloroquine compared to those who did not (OR 1.1, 95% CI: 0.6 to 2.02; p = 0.76). Viral clearance, assessed by RT-PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 1.13, CI: 0.26 to 5.01; p = 0.87). The evolution of changes on chest CT imaging was reported only in two studies; a more pronounced improvement was observed with the use of hydroxychloroquine compared to standard care (OR: 2.68, CI: 1.1 to 6.6; P = 0.03). The incidence of adverse events was significantly higher with hydroxychloroquine (OR: 4.1, CI: 1.42 to 11.88; p = 0.009). Conclusions Our meta-analysis does not suggest improvement in clinical progression, mortality, or viral clearance by RT PCR among patients with COVID 19 infection who are treated with hydroxychloroquine. There was a significantly higher incidence of adverse events with hydroxychloroquine use.

IMPORTANCEAccurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured.OBJECTIVE To externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated score with currently accepted HCC selection tools, namely, the Milan Criteria (MC), the French-AFP (F-AFP), and Metroticket 2.0 models. DESIGN, SETTING, AND PARTICIPANTSA retrospective, multicenter prognostic analysis of prospectively collected databases of 2236 adults undergoing liver transplant for HCC was conducted at 3 US, 1 Canadian, and 4 European centers from January 1, 2001, to December 31, 2013. The AFP-R was measured as the difference between maximum and final pre-liver transplant AFP level. Cox proportional hazards regression and competing risk regression analyses examined recurrence-free and overall survival. Receiver operating characteristic analyses and net reclassification index were used to compare NYCA with MC, F-AFP, and Metroticket 2.0. Data analysis was performed from June 2019 to April 2020. MAIN OUTCOMES AND MEASURESThe primary study outcome was 5-year recurrence-free survival; overall survival was the secondary outcome. RESULTSOf 2236 patients, 1808 (80.9%) were men; mean (SD) age was 58.3 (7.96) years. A total of 545 patients (24.4%) did not meet the MC. The NYCA score proved valid on competing risk regression analysis, accurately predicting recurrence-free and overall survival (5-year cumulative incidence of recurrence risk in NYCA risk categories was 9.5% for low-, 20.5%, for acceptable-, and 40.5% for high-risk categories; P < .001 for all). The NYCA also predicted recurrence-free survival on a center-specific level: 453 of 545 patients (83.1%) who did not meet MC, 213 of 308 (69.2%) who did not meet the French-AFP, 292 of 384 (76.1%) who did not meet Metroticket 2.0 would be recategorized into NYCA low-and acceptable-risk groups (>75% 5-year recurrence-free survival). The Harrell C statistic for the validated NYCA score was 0.66 compared with 0.59 for the MC and 0.57 for the F-AFP models (P < .001). The net reclassification index for NYCA was 8.1 vs MC, 12.9 vs F-AFP, and 10.1 vs Metroticket 2.0. CONCLUSIONS AND RELEVANCEThis study appears to externally validate the importance of AFP-R in the selection of patients with HCC for liver transplant. The AFP-R represents one of the truly objective measures of biological characteristics available before transplantation. Incorporation of AFP-R into selection criteria allows safe expansion of MC and other models, offering liver transplant to patients with acceptable...

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There is increasing interest in the use of ultrasound to assess and guide the management of critically ill patients. The ability to carry out quick examinations by the bedside to answer specific clinical queries as well as repeatability are clear advantages in an acute care setting. In addition, delays associated with transfer of patients out of the Intensive Care Unit (ICU) and exposure to ionizing radiation may also be avoided. Ultrasonographic imaging looks set to evolve and complement clinical examination of acutely ill patients, offering quick answers by the bedside. In this two-part narrative review, we describe the applications of ultrasonography with a special focus on the management of the critically ill. Part I explores the utility of echocardiography in the ICU, with emphasis on its usefulness in the management of hemodynamically unstable patients. We also discuss lung ultrasonography - a vastly underutilized technology for several years, until intensivists began to realize its usefulness, and obvious advantages over chest radiography. Ultrasonography is rapidly emerging as an important tool in the hands of intensive care physicians.

We report a case of “Apical Ballooning Syndrome” following attempted suicidal hanging. Our patient developed retrosternal chest pain and ischemic changes on electrocardiography (ECG), a day after the suicidal attempt. She underwent an angiogram considering the possibility of acute coronary syndrome. However, her coronary arteries were normal; the left ventricle showed the typical ballooning pattern characterized by hypokinesia of the distal septum and apex. On follow-up a week later, she remained asymptomatic; her ECG changes had reversed and the left ventricular contractility was normal on echocardiography.

646 Background: The efficacy of immune checkpoint inhibitor has been limited to small portion of colorectal cancer (CRC) patients whose tumors with mismatch repair (MMR) gene abnormalities. There is an urgent need for patients with MMR proficient (pMMR) tumors. Oncolytic immunotherapy represents a novel therapeutic platform for the treatment of cancer with unique activity compared to conventional chemotherapy. The trial is to evaluate if the combination of Pexa-Vec oncolytic virus (PV) with immune checkpoint inhibition enhance antitumor immunity. Methods: Patients with microsatellite-stable and MSI-H mCRC refractory to PD-1 monotherapy were enrolled. Patients received either Arm A treated with PV + Durvalumab or Arm B with PV + Durvalumab and Tremelimumab. Each arm had two dose levels (DL) of PV, 3 x 108 pfu in DL1 and at 109 pfu in DL2, every 2 weeks for total 4 doses. The first dose of PV was administered on Day -12, followed by three more dose administration on Days 2, 16 and 30 in combination with the immune checkpoint inhibition. The primary endpoint is response rate, safety, tolerability and feasibility of these combination therapy in refractory metastatic CRC. Results: Here we report the safety data of Arm A.A total of 9 patients was enrolled so far. The longest follow-up time is 8 months. Four patients received DL1 PV and subsequent five patients received DL2 PV. No DLT was observed at the time of this abstract. No grade 4-5 adverse event (AE) were observed. All patients experienced lymphopenia. All patients with DL2 developed fever, hypotension and papulopastular rashes and were successfully managed with antipyretics, fluid support and skin protection, respectively. The most frequent treatment-related AEs were lymphopenia (8 [100%], fever (7 [87.5%]), chills (6 [75.0%]), hypotension (5 [62.5%]), papulopastular rashes (5 [62.5%], flu-like symptoms (2 [12.5%]), Nausea/vomiting (2 [12.5%]). Conclusions: Pexa-Vec in combination with Durvalumab showed a favorable safety profile. Clinical trial information: NCT03206073.

Anemia of multifactorial etiology is common among critically ill patients and several arbitrary transfusion thresholds have been proposed. Transfusion of red blood cells has been well established to increase morbidity and even mortality among critically ill patients. Several randomized controlled studies have evaluated the use of a restrictive compared to a more liberal transfusion strategy in the critically ill. A transfusion threshold of 7 g/dL appears to be generally safe, especially in the younger age group without significant comorbidities. Besides, a restrictive transfusion strategy reduces the incidence of transfusion-related complications. However, the decision to transfuse needs to be individualized depending on the clinical situation, balancing putative benefits against possible complications.How to cite this articleChacko J, Brar G. Red Blood Cell Transfusion Thresholds in Critically Ill Patients. Indian J Crit Care Med 2019;23(Suppl 3):S181–S184.

Paralysis of the lower cranial nerves is uncommon after closed head injuries. Most cases reported are unilateral and associated with base of skull fractures, usually involving the occipital condyles. Bilateral lower cranial nerve palsy is even less common, with only a handful of cases reported in literature. A 17-year-old girl presented to us after she was involved in a side-on collision with a car while driving a scooter. She sustained traumatic brain injury requiring mechanical ventilation. Detailed neurological evaluation revealed bilateral paralysis of the IXth, Xth, and XIIth cranial nerves with no evidence of a fracture of the base of skull or brain stem injury. A traction type of injury to the nerves arising from a whiplash mechanism may have led to paralysis of the lower cranial nerves in our patient. An exhaustive review of literature revealed 11 reports of bilateral lower cranial nerve palsy associated with closed head injuries; there were only four cases without underlying fracture of the occipital condyles. Our patient made a complete recovery over a period of 4 months. A traction type of injury to the lower cranial nerves may occur due to a whiplash mechanism. This type of injury may be associated with a favorable outcome.