Oncometabolite 2-hydroxyglutarate suppresses basal protein levels of DNA polymerase beta that enhances alkylating agent and PARG inhibition induced cytotoxicity.

Mutations in isocitrate dehydrogenase isoform 1 (IDH1) are primarily found in secondary glioblastoma (GBM) and low-grade glioma but are rare in primary GBM. The standard treatment for GBM includes radiation combined with temozolomide, an alkylating agent. Fortunately, IDH1 mutant gliomas are sensitive to this treatment, resulting in a more favorable prognosis. However, it's estimated that up to 75 % of IDH1 mutant gliomas will progress to WHO grade IV over time and develop resistance to alkylating agents. Therefore, understanding the mechanism(s) by which IDH1 mutant gliomas confer sensitivity to alkylating agents is crucial for developing targeted chemotherapeutic approaches. The base excision repair (BER) pathway is responsible for repairing most base damage induced by alkylating agents. Defects in this pathway can lead to hypersensitivity to these agents due to unresolved DNA damage. The coordinated assembly and disassembly of BER protein complexes are essential for cell survival and for maintaining genomic integrity following alkylating agent exposure. These complexes rely on poly-ADP-ribose formation, an NAD+-dependent post-translational modification synthesized by PARP1 and PARP2 during the BER process. At the lesion site, poly-ADP-ribose facilitates the recruitment of XRCC1. This scaffold protein helps assemble BER proteins like DNA polymerase beta (Polß), a bifunctional DNA polymerase containing both DNA synthesis and 5'-deoxyribose-phosphate lyase (5'dRP lyase) activity. Here, we confirm that IDH1 mutant glioma cells have defective NAD+ metabolism, but still produce sufficient nuclear NAD+ for robust PARP1 activation and BER complex formation in response to DNA damage. However, the overproduction of 2-hydroxyglutarate, an oncometabolite produced by the IDH1 R132H mutant protein, suppresses BER capacity by reducing Polß protein levels. This defines a novel mechanism by which the IDH1 mutation in gliomas confers cellular sensitivity to alkylating agents and to inhibitors of the poly-ADP-ribose glycohydrolase, PARG.

Meningeal lymphatic CGRP signaling governs pain via cerebrospinal fluid efflux and neuroinflammation in migraine models.

Recently developed anti-migraine therapeutics targeting calcitonin gene-related peptide (CGRP) signaling are effective, though their sites of activity remain elusive. Notably, the lymphatic vasculature is responsive to CGRP signaling, but whether meningeal lymphatic vessels (MLVs) contribute to migraine pathophysiology is unknown. Mice with lymphatic vasculature deficient in the CGRP receptor (CalcrliLEC mice) treated with nitroglycerin (NTG)-mediated chronic migraine exhibit reduced pain and light avoidance compared to NTG-treated littermate controls. Gene expression profiles of lymphatic endothelial cells (LECs) isolated from the meninges of Rpl22HA/+;Lyve1Cre RiboTag mice treated with NTG revealed increased MLV-immune interactions compared to cells from untreated mice. Interestingly, the relative abundance of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM1)-interacting CD4+ T cells was increased in the deep cervical lymph nodes of NTG-treated control mice but not in NTG-treated CalcrliLEC mice. Treatment of cultured hLECs with CGRP peptide in vitro induced vascular endothelial (VE)-cadherin rearrangement and reduced functional permeability. Likewise, intra cisterna magna injection of CGRP caused rearrangement of VE-Cadherin, decreased MLV uptake of cerebrospinal fluid (CSF), and impaired CSF drainage in control mice, but not in CalcrliLEC mice. Collectively, these findings reveal a previously unrecognized role for lymphatics in chronic migraine, whereby CGRP signaling primes MLVs-immune interactions and reduces CSF efflux.

Video Versus Direct Laryngoscopy for Intubation: Updated Systematic Review and Meta-Analysis.

Direct laryngoscopy (DL) is a modality commonly used in endotracheal intubation (EI). Video laryngoscopy (VL) was introduced to further facilitate the procedure with enhancement in glottic views, which captures the video image of the vocal cords to be projected onto a screen, providing enhanced visualization. This real-time video projection aids in accurately placing the endotracheal tube (ETT) through the vocal cords. In emergency and critical care settings, both laryngoscopes are used for intubations. This study assesses the efficacy of both modalities by comparing success rates in first-attempt tracheal intubation in critically ill patients.  PubMed, EMBASE, and Scopus were searched and all randomized controlled trials (RCTs) and observational studies until 2023 were included. Studies included patients in critical care settings undergoing EI under the guidance of either DL or VL. The primary outcome was the first attempt at successful tracheal intubation. The secondary outcomes assessed the comparative safety of DL and VL by comparing the rates of severe hypoxemia, severe hypotension, and cardiac arrest occurring during each modality. P-values were considered of statistical significance if below 0.05. Statistical analysis was performed using RevMan v5.4 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). The results were displayed in the form of forest plots.  A total of eight studies were included with a total of 5348 patients, with 1780 in the DL group and 3568 in the VL group. Analysis revealed that in emergency situations, the success rate of intubation on the first attempt was significantly higher for VL than DL [81.5% vs 68%; RR= 1.19; 95% CI: 1.10, 1.29; p <0.00001; I2=70%]. There was no significant correlation between VL and severe hypoxemia [13.4% vs 11.6%; RR= 0.99; 95% CI: 0.74, 1.33; p =0.97; I2=46%], severe hypotension [6.09% vs 4.78%; RR:1.19; 95% CI: 0.83, 1.72; p =0.35, I2-15%], and cardiac arrest, [0.8% vs 0.4%; RR= 1.17; 95% CI: 0.37, 3.70]; p =0.79; I2=0%]. Our meta-analysis confirmed that VL has a higher success rate for first-pass intubation than DL. Furthermore, our analysis has shown no significant evidence linking VL to any adverse events.

Breast cancer's hidden partner: meningoencephalitis as a paraneoplastic revelation: a rare presentation of invasive ductal carcinoma of breast: a case report.

Introduction and importance: Paraneoplastic neurologic syndromes encompass a group of neurologic disorders arising from pathological processes unrelated to metastasis, metabolic disturbances, infections, coagulopathy, or treatment-related side effects. These syndromes can affect various regions of the nervous system, resulting in diverse clinical manifestations. Case presentation: The authors present a rare case of anti-amphiphysin-associated meningoencephalitis in a South Asian Pakistani woman. Initially, the patient was managed for suspected infectious meningitis, but empirical treatment failed to yield improvement. Subsequent investigations unveiled a paraneoplastic syndrome secondary to breast cancer. Discussion: Diagnosing these clinical entities is challenging due to their multifaceted presentations, often leading to delayed identification, increased patient suffering, economic burdens, and preventable complications. Conclusion: Anti-amphiphysin-associated meningoencephalitis is a rare manifestation of paraneoplastic syndromes. It is crucial to raise awareness among healthcare professionals about the diverse presentations of paraneoplastic syndromes.

Therapeutic Outcomes Following Isolated Transcatheter Tricuspid Valve Repair: A Systematic Review and Meta-analysis.

Tricuspid regurgitation (TR) is traditionally treated surgically, but isolated transcatheter tricuspid valve repair (ITTVR) offers a less invasive option. This study conducts a meta-analysis and systematic review to evaluate ITTVR outcomes in patients with TR. Database searches until March 2023 identified studies assessing ITTVR safety and efficacy in moderate/severe TR patients. Primary outcomes analyzed were severe TR, NYHA functional class improvement, and 6-minute walking distance. Meta-analyses used Risk ratio (RR) or mean difference with a random effects model. The review included 25 studies with 2421 patients. ITTVR improved NYHA functional class (RR: 3.262), reduced TR severity (RR: 0.303), and enhanced 6-minute walking distance (MD: +47.077 m). Echocardiographic parameters improved, including reductions in TR vena contracta, TR EROA, septolateral tricuspid annular diameter, RVEDD, RV FAC, and TAPSE. LVEF and PASP showed no significant changes. ITTVR improves functional outcomes and echocardiographic parameters in TR patients.

Demographics and Characteristics of Acutely Decompensated Heart Failure (ADHF) Patients in a Tertiary Care Center in Saudi Arabia.

BACKGROUND: Acute decompensated heart failure (ADHF) has been defined as the gradual or rapid change in heart failure (HF) signs and symptoms resulting in a need for urgent therapy. Patients with ADHF usually have multiple comorbidities that contribute to the severity of exacerbation at admission, including diabetes mellitus and chronic kidney disease. The prognosis for these individuals is generally poor, with a high risk of readmission and death after discharge. Unfortunately, there are limited studies in Saudi Arabia reporting the characteristics of such patients. We aim to study the demographics and characteristics of ADHF patients admitted to King Abdulaziz University Hospital (KAUH) and analyze gender discrepancies and in-hospital mortality. METHODS: This retrospective record review was conducted at KAUH. The study included 425 patients diagnosed with ADHF. The New York Heart Association (NYHA) classification, underlying etiology of HF, comorbidities, left ventricular ejection fraction (LVEF), vital signs, comprehensive metabolic panel at admission, and in-hospital mortality were evaluated and analyzed. RESULTS: The majority of the patients were males (52.5%), and the average age was 63 ± 13.75 years. The most prevalent etiology of HF was hypertensive heart disease (51.8%), followed by ischemic heart disease (42.8%). The most common comorbidity was diabetes mellitus (73.6%), and the most common medication administered was diuretics (95.5%). The mean LVEF was 37.9% ± 16.0. In-hospital mortality occurred in 10.4% of patients. The mean length of hospitalization was 16.7 ± 86.2 days. The mean blood urea nitrogen (BUN) (17.18 ± 11.16) and creatinine (243.34 ± 222.27) were higher in patients with in-hospital mortality. The mean difference was statistically significant (P = 0.003 and P = 0.014). A higher length of hospitalization was significantly associated with in-hospital mortality (P = 0.036). CONCLUSION: We found more than half of our sample to be males and diabetes mellitus to be common among ADHF patients. Elevated BUN and creatinine levels at the time of presentation, as well as patients who had been in the hospital for a more extended period of time, were found to be associated with an increased risk of in-hospital mortality.

Behavioural, genomics and proteomic approach to examine Alzheimer's disease in zebrafish.

Globally around 24 million elderly population are dealing with dementia, and this pathological characteristic is commonly seen in people suffering from Alzheimer's disease (AD). Despite having multiple treatment options that can mitigate AD symptoms, there is an imperative call to advance our understanding of the disease pathogenesis to unfold disease-modifying treatments/therapies. To explore the driving mechanisms of AD development, we stretch out further to study time-dependant changes after Okadaic acid (OKA)-induced AD-like conditions in zebrafish. We evaluated the pharmacodynamics of OKA at two-time points, i.e., after 4-days and 10-days exposure to zebrafish. T-Maze was utilized to observe the learning and cognitive behaviour, and inflammatory gene expressions such as 5-Lox, Gfap, Actin, APP, and Mapt were performed in zebrafish brains. To scoop everything out from the brain tissue, protein profiling was performed using LCMS/MS. Both time course OKA-induced AD models have shown significant memory impairment, as evident from T-Maze. Gene expression studies of both groups have reported an overexpression of 5-Lox, GFAP, Actin, APP, and OKA 10D group has shown remarkable upregulation of Mapt in zebrafish brains. In the case of protein expression, the heatmap suggested an important role of some common proteins identified in both groups, which can be explored further to investigate their mechanism in OKA-induced AD pathology. Presently, the preclinical models available to understand AD-like conditions are not completely understood. Hence, utilizing OKA in the zebrafish model can be of great importance in understanding the pathology of AD progression and as a screening tool for drug discovery.

Contagion of coronavirus disease-the first family cluster of Pakistan: a case series.

Coronavirus Disease has resulted in public health crisis all over the world. We describe the case series of a family, who travelled together to a mass gathering in Iraq, toured Syria, Lebanon, and Doha and returned to Karachi. The data describes the demographic and clinical features of these six members. There were three males and three females. One developed severe disease and died. Incubation period was between 8-14 days. Four patients were symptomatic, had diabetes mellitus and hypertension; and presented with fever. They also had bilateral airspace opacifications on chest X-ray. Our study describes familial clustering of SARS-CoV-2 and its person-to-person transmission.

Levosimendan: mechanistic insight and its diverse future aspects in cardiac care.

Inotropic agents are generally recommended to use in patients with acute decompensated heart failure (HF) with reduced ejection fraction (HFrEF) concurrent to end-organ dysfunction. However, due to certain pharmacological limitations like developing life threatening arrhythmia and tolerance, cannot be employed as much as needed. Meanwhile, Calcium ion (Ca2+) sensitisers exhibits their inotropic action by increasing the sensitivity of the cardiomyocyte to intracellular Ca2+ ion and have been reported as emerging therapeutic alternative in HF cases. Levosimendan (LEVO) is an inodilator and with its unique pharmacology justifying its use in a wide range of cardiac alterations in HF particularly in undergoing cardiac surgery. It is also reported to be better than classical inotropes in maintaining cardiac mechanical efficacy and reducing congestion in acute HF with hypotension. This review paper was designed to compile various evidence about basic pharmacology and potential clinical aspects of LEVO in cardiac surgery and other HF associated alterations. This will benefit directly to the researcher in initiating research and to fill the gaps in the area of thrust.

Clinical Features and Outcomes of Acute Chlorine Gas Inhalation; a Brief Report.

Introduction: On March 6th,2020, chlorine gas leak was reported at Engro Polymer & Chemicals Plant in Karachi City, Pakistan. This study aimed to evaluate the clinical features and outcomes of patients who presented to emergency department (ED) following this event. Methods: This retrospective cross-sectional study, evaluated the clinical features and outcomes (length of hospital stay, complications, and mechanical ventilation requirement) of patients presenting to ED of Aga Khan University Hospital, Karachi, Pakistan, with history of chlorine gas exposure at the Engro Plant from 6th March to 14th March 2020. Results: 38 patients with mean age of 33.1 ± 8.1 years presented to ED with history of chlorine gas exposure (100% male). 4 (10.5%) cases had comorbid diseases. Most common presenting symptom was dyspnea, observed in 33 (86.8%) cases, followed by cough, seen in 27 (71.1%) subjects. 13.2% (5/38) patients had infiltration on chest x-ray and 33 (86.8 %) required hospitalization. 6 (15.8%) patients had repeat presentation requiring hospitalization or ED visit. 18 (47.4%) were managed with high flow oxygen therapy, 9 (23.7%) required non-invasive ventilation and one patient was intubated due to development of pneumo-mediastinum. Mean length of stay was 1.55 ± 1.58 days and no patients died. Presence of tachycardia was the only finding significantly associated with need for oxygen (p = 0.033) and non-invasive ventilation (p = 0.012). Conclusion: The majority of patients presenting with acute chlorine gas exposure showed good clinical outcomes and rapid recovery, however, a high index of suspicion and vigilance should be maintained for complications such as pneumomediastinum and acute respiratory distress syndrome in these patients.

COVID-19 encephalopathy: an unusual presentation with new-onset seizure causing convulsive status epilepticus.

Although neurological manifestations such as headache and myalgias have been observed with COVID-19, presentation with more serious neurological illness is uncommon and rare. We report a case of a middle-aged woman who presented to the emergency department of a tertiary care hospital. Her clinical presentation was primarily neurological rather than the more common presentation with respiratory manifestations. She presented with generalised tonic-clonic seizures, along with history of undocumented low-grade fever and generalised body aches. The positive SARS-CoV-2 RT-PCR nasal swab, the cerebrospinal fluid analysis (lymphocytic pleocytosis) and electroencephalogram were consistent with viral encephalitis; brain imaging was unremarkable. This case highlights the variable presenting features of COVID-19 infection as patients can primarily present with neurological manifestations in the absence of significant respiratory symptoms. We believe it is important to recognise neurological disease associated with SARS-CoV-2 in patients with asymptomatic respiratory infection.

Invasive pulmonary aspergillosis in critically ill patients with pneumonia due to COVID-19, influenza, and community-acquired pneumonia: A prospective observational study.

Background and Purpose: Influenza A and SARS-CoV-2 are risk factors for invasive pulmonary aspergillosis. Both influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis result in high mortality and poor clinical outcomes. No prospective study has so far compared the features, treatment, and outcomes of influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis within a similar time frame. Therefore, this study aimed to determine the frequency, risk factors, and outcomes of invasive pulmonary aspergillosis in critically ill patients with influenza, COVID-19, and community-acquired pneumonia. Materials and Methods: This prospective study included adult patients with pneumonia and was conducted at The Aga Khan University Hospital in Karachi, Pakistan. Patients were divided into three groups, including community-acquired pneumonia, influenza pneumonia, and COVID-19 pneumonia. The data collected included information on demographic characteristics, comorbidities, clinical features, laboratory results, treatment, and outcomes. Results: A total of 140 patients were included in this study. These included 35 (25%), 70 (50%), and 35 (25%) patients with community-acquired pneumonia, influenza pneumonia, and COVID-19 pneumonia, respectively. In addition, 20 (14.2%) patients were found to have invasive aspergillosis, of whom 10/35 (28.5%), 9/70 (12.8%), and 1/35 (2.8%) patients were in the COVID-19, influenza, and community-acquired pneumonia groups, respectively. Moreover, nine (90%) COVID-19-associated pulmonary aspergillosis patients required vasopressors, compared to three (33%) patients with influenza-associated pulmonary aspergillosis (P=0.020). In total, seven (70%) COVID-19-associated pulmonary aspergillosis patients required invasive mechanical ventilation compared to four (44%) influenza-associated pulmonary aspergillosis patients (P=0.37). The mean±SD length of hospital stay was highest in the COVID-19-associated pulmonary aspergillosis patients (18.3±7.28 days) compared to influenza-associated pulmonary aspergillosis patients (11.7±5.34 days) (P=0.036). The number of deaths in influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis patients was three (33.3%) and five (50%), respectively (P=0.526). Conclusion: A higher proportion of patients with COVID-19 developed invasive aspergillosis compared to those with influenza. Although the mortality rate in COVID-19-associated pulmonary aspergillosis was comparable to that in influenza-associated pulmonary aspergillosis patients, COVID-19-associated pulmonary aspergillosis patients had a significantly longer stay in the hospital.

Mechanistic role of boswellic acids in Alzheimer's disease: Emphasis on anti-inflammatory properties.

The resin/gum of Boswellia species belonging to the family of Burseraceae is a naturally occurring mixture of bioactive compounds, which was traditionally used as a folk medicine to treat conditions like chronic inflammation. Several research studies have also explored its' therapeutic potential against multiple neurodegenerative diseases such as Alzheimer's disease (AD). The main chemical constituents of this gum include boswellic acids (BAs) like 3-O-acetyl-11-keto-ß boswellic acid (AKBA) that possess potent anti-inflammatory and neuroprotective properties in AD. It is also involved in inhibiting the acetylcholinesterase (AChE) activity in the cholinergic pathway and improve choline levels as well as its binding with nicotinic receptors to produce anti-inflammatory effects. Multiple shreds of evidence have demonstrated that BAs modulate key molecular targets and signalling pathways like 5-lipoxygenase/cyclooxygenase, Nrf2, NF-kB, cholinergic, amyloid-beta (Aß), and neurofibrillary tangles formation (NFTs) that are involved in AD progression. The present review focuses on the possible mechanistic therapeutic role of BAs in modulating the 5-LOX/COX pathway in arachidonic acid metabolism, activating Nrf2 through binding of ARE, inhibiting NF-kB and AChE activity. In addition, an inhibition of amyloid plaques (Aß) and neurofibrillary tangles (NFTs) induced neurotoxicity and neuroinflammation in AD by BAs is also discussed in this review. We have also highlighted that BAs possess beneficial effects in AD by targeting multiple molecular pathways and makes it an emerging drug candidate for treating neurodegenerative diseases.

Blood pressure control measured as "time in range" during initial 24 h for inpatients with spontaneous nontraumatic intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Blood pressure (BP) control is an integral part in the management of spontaneous nontraumatic intracerebral haemorrhage. The aim of this study is to propose a novel concept of blood pressure control measured as 'Time in Range'(TiR) and assess its relationship to neurological deterioration. METHOD: Retrospective study of 120 patients with Intracerebral haemorrhage who were admitted within 6 h of the symptom onset. The hourly BP readings for initial 24 h were studied in the form of time in range (TiR). TiR was defined as the percentage of readings with 'in range' systolic BP (SBP 110-140mmHG) during a unit time period. TiR was correlated with mean SBP at 6,12,18 and 24 h. It was categorized dichotomously as controlled (more than 50%) or not controlled (equal to or less than 50%) and analyzed with the change in Glasgow coma scale (drop of ≥2 units) at 24 h. RESULTS: Correlation of TiR with mean SBP at 6 and 24 h showed significant negative correlation [r = -0.71 (at 6 h); r = -0.88 (at 24 h); p < 0.001]. The association of TiR with neurological deterioration(ND) was measured by change in GCS; with lower TiR associated with higher chances of neurological deterioration at 12 h interval [OR 4.5(1.2-16.8); p = 0.025], but not at 24 h interval [OR 1.4 (0.34-5.44); p = 0.670]. CONCLUSION: Our novel concept of 'Time in Range'(TiR) was found to be relevant in our study. Its association with mean SBP reflect its potential to be a modality of expressing control of SBP in Spontaneous Nontraumatic Intracerebral Haemorrhage.

Inflammation Drives Alzheimer's Disease: Emphasis on 5-lipoxygenase Pathways.

It is a known fact that inflammation affects several physiological processes, including the functioning of the central nervous system. Additionally, impairment of lipid mechanisms/pathways have been associated with a number of neurodegenerative disorders and Alzheimer's Disease (AD) is one of them. However, much attention has been given to the link between tau and beta- amyloid hypothesis in AD pathogenesis/prognosis. Increasing evidences suggest that biologically active lipid molecules could influence the pathophysiology of AD via a different mechanism of inflammation. This review intends to highlight the role of inflammatory responses in the context of AD with the emphasis on biochemical pathways of lipid metabolism enzyme, 5-lipoxygenase (5- LO).

Undiagnosed Acquired Hemophilia A: Presenting as Recurrent Gastrointestinal Bleeding.

Acute gastrointestinal bleeding (GIB) is a frequently encountered medical emergency and it can be life-threatening depending on the etiology and the clinical condition of the patient. The most common causes of GIB are peptic ulcer disease, aspirin-induced gastritis, variceal hemorrhage, esophagitis, neoplasms like gastric cancer. Acquired hemophilia causing acute gastrointestinal bleed is extremely rare and only a few cases are reported worldwide. Acquired hemophilia A (AHA) is a rare disorder caused by the production of autoantibodies that inactivates clotting factor VIII. We present a case of upper gastrointestinal bleed due to AHA which was undiagnosed for two years. A 74-year-old patient with a history of myasthenia gravis, presented with anemia, and GIB. She underwent multiple endoscopies without a clear bleeding source. Coagulation studies showed isolated activated partial thromboplastin time prolongation which was not corrected by mixing study. Factor VIII activity was low and Bethesda titer showed elevated inhibitor levels. Factor Eight Bypassing Agent, recombinant factor VIIa, and steroids were given to control bleeding. Her clinical condition worsened, and she passed away. Elderly patients presenting with an undiagnosed source of GIBs, inconclusive endoscopic studies should be evaluated for acquired coagulopathies, especially in those with a history of autoimmune diseases and malignancies. Prompt diagnosis and treatment are warranted as it carries a high mortality. Part of the case presentation was presented as an abstract at a regional conference.

COVID-19-Induced Diabetic Ketoacidosis and Acute Respiratory Distress Syndrome in an Obese 24-Year-Old Type I Diabetic.

BACKGROUND In early 2020, severe acute respiratory syndrome-corona virus 2 caused an outbreak of a viral pneumonia that rapidly progressed to a global pandemic. Most cases presented with mild respiratory symptoms and required only supportive care with instructions to self-quarantine at home. Others had more severe symptoms that became complicated by acute respiratory distress syndrome (ARDS) and required hospitalization. CASE REPORT In this report, we present the case of a young patient in New York City who presented to our hospital with coronavirus disease 2019-induced diabetic ketoacidosis (DKA) that progressed to ARDS and subsequent death. The patient was managed for DKA on presentation with insulin protocol and acidosis management. However, it became evident that he had underlying respiratory complications, which later presented as ARDS requiring mechanical ventilation and antibiotics. CONCLUSIONS We recommend that clinicians be aware of this potentially fatal complication in all patients with pre-existing diabetes. Simultaneously, a low threshold for intubation should be advocated for patients with concurrent COVID-19 and type I diabetes mellitus since the potential for poor clinical outcomes from respiratory demise may be lessened by early respiratory intervention.

What are we missing? Three cases of severe COVID-19 pneumonia with negative testing.

The COVID-19 pandemic has drastically affected health care systems globally. Reverse transcriptase-polymerase chain reaction is currently the preferred method of detecting COVID-19; however, sensitivity of this test remains questionable. Incidental transmission and potential harm to infected individuals are some consequences of the failure to identify high-risk patients. We report three cases of symptomatic patients that required intensive care management with labs and imaging consistent with COVID-19 with initial false-negative reverse transcriptase-polymerase chain reaction testing. Improper sampling, viral load, and manufacturer variances of tests all contribute to reduced sensitivity. A clinical diagnosis should supplant such cases.

It's complicated: A case report on a COVID-19-positive HIV patient presenting with rhabdomyolysis and acute kidney injury.

The SARS-Cov-2/COVID-19 pandemic in early 2020 has had a devastating impact on health systems around the world. While viral pneumonia remains the most common complication, reports are surfacing of cases with neurological, cardiac, and renal involvement. Even less is known about the implications in special high-risk populations. In this report, we discuss a unique case of an HIV-positive patient in New York City who presented with a 2-week history of worsening fatigue, cough, dyspnea, and myalgias and was found to have COVID-19 pneumonia and acute kidney injury. He was managed for severe uremic metabolic acidosis and electrolyte abnormalities with emergent hemodialysis and supportive therapy with subsequent improvement. Direct involvement of SARS-CoV-2 and pneumonia-induced rhabdomyolysis were identified as the precipitating factors of his acute kidney injury. The pathophysiologic mechanisms of acute kidney injury, SARS-CoV-2 renal tropism, and the impact of highly active antiretroviral therapy on COVID-19 pneumonia are discussed. We highlight the importance of clinician awareness of this potentially fatal complication of COVID-19 pneumonia, particularly in the HIV-positive population as early recognition and management can have favorable outcomes.