Potential Association of Remdesivir and Hyperkalemia: A Disproportionality Analysis in USFDA Adverse Event Reporting System Database

Background: Signal detection is one of the most advanced and promising techniques in the world of pharmacovigilance. Remdesivir is approved for emergency use by the US Food and Drug Administration (FDA) for patients with coronavirus disease 2019 (COVID-19). Its benefit- risk ratio is still being explored because data in the field are rather scant. On the other hand hyperkalemia is a potentially life-threatening electrolyte disorder. Severe hyperkalemia can occur suddenly and can cause life-threatening heart rhythm changes (arrhythmia) that cause a heart attack. Even mild hyperkalemia can cause heart related problems over time if not treated. Objective(s): To evaluate the potential association of Remdesivir with risk of Hyperkalemia by analyzing the spontaneous reports through disproportionality analysis. Method(s): Data were obtained from the public release of data in FAERS. Case/non-case method was adopted for the analysis of association between Remdesivir use and Hyperkalemia. The data-mining algorithm used for the analysis were Reporting Odds Ratio(ROR) and Proportional Reporting Ratio (PRR). A value of ROR-1.96SE>, PRR>=2 were considered as positive signal. Result(s): A total of 7 DE's associated with Remdesivir use and hyperkalemia were reported. The mean age of the patients of Remdesivir associated events was found to be 75 years [95% CI]. The reports by gender were distributed with a male to female ratio of 3:1, though gender was not revealed in 3 reports. The data mining algorithms exhibited positive signal for hyperkalemia (PRR: 2.349, ROR: 2.354) upon analysis as those were well above the pre-set threshold. Three case reports were identified which strengthened these findings and highlighted the importance of laboratory parameters for the early detection of hyperkalemia Conclusion(s): The current study found a potential risk of hyperkalemia with the use of Remdesivir and there is an urgent need to thoroughly investigate the same and take the necessary action to avoid or minimize the risk.Copyright © 2023

Spectrum of Biochemical Alterations in Patients with Covid-19

Background and objective: Millions of people worldwide have died from COVID-19, which has caused the failure of the lungs and other organs. The research assessed biochemical anomalies in COVID-19 patients to comprehend the illness and its effect better. Study Design: Retrospective longitudinal cohort analysis Place of study: ABWA Medical College Faisalabad Methods: A total of 150 adult patients (n=150) who tested positive for COVID-19 via RT-PCR were included in the study. A Roche Diagnostics Cobas C501 used spectrophotometry to measure calcium, magnesium, phosphate, lactate dehydrogenase (LDH), urea, creatinine, ferritin, and chloride in the blood. A NOVA electrolytic analyzer used Ion-selective electrodes to measure sodium, chloride, potassium, and bicarbonate. Result(s): In the study, 33.6% of patients had elevated urea levels, and 22.4% had elevated creatinine levels. Furthermore, 88.8% of patients had elevated ferritin levels, and 93.5% had elevated LDH levels. After 44 weeks, there was a drop in sodium-containing electrolytes, with 9% of patients experiencing a decrease in sodium, 22.4% in potassium, 53.3% in bicarbonate, 48.6% in calcium, and 23.4% in phosphorus. These changes in electrolyte levels suggest a long-term trend in electrolyte depletion among the patient population. There was no significant difference in biochemical anomalies between age groups (p > 0.05). Conclusion(s): These results suggest that COVID-19 patients have lung illness and multi-organ involvement, which should be considered when managing these patients. These biochemical alterations warrant careful monitoring for organ failure by healthcare practitioners. More study is required to comprehend the processes causing these biochemical anomalies in COVID-19 patients.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

The Association between Dysnatraemia during Hospitalisation and Post-COVID-19 Mental Fatigue.

COVID-19 may induce short- and long-term cognitive failures after recovery, but the underlying risk factors are still controversial. Here, we investigated whether (i) the odds of experiencing persistent cognitive failures differ based on the patients' disease course severity and sex at birth; and (ii) the patients' electrolytic profile in the acute stage represents a risk factor for persistent cognitive failures. We analysed data from 204 patients suffering from COVID-19 and hospitalised during the first pandemic wave. According to the 7-point WHO-OS scale, their disease course was classified as severe or mild. We investigated the presence of persistent cognitive failures collected after hospital discharge, while electrolyte profiles were collected during hospitalisation. The results showed that females who suffered from a mild course compared to a severe course of COVID-19 had a higher risk of presenting with persistent mental fatigue after recovery. Furthermore, in females who suffered from a mild course of COVID-19, persistent mental fatigue was related to electrolyte imbalance, in terms of both hypo- and hypernatremia, during hospitalisation in the acute phase. These findings have important implications for the clinical management of hospitalised COVID-19 patients. Attention should be paid to potential electrolyte imbalances, mainly in females suffering from mild COVID-19.

The Impact of Regional Citrate Anticoagulation on Magnesium Replacement During CRRT.

A patient admitted to the ICU with shock and acute kidney injury required continuous renal replacement therapy (CRRT). CRRT was initiated using regional citrate anticoagulation (RCA) with an initial magnesium (Mg) level of 1.7 mg/dL. Over 12 days the patient received 68 g of Mg sulfate. After 58 g the patient's Mg level was 1.4 mg/dL. On day 13, CRRT was changed to a heparin circuit from concerns of citrate toxicity. Over the next 7 days the patient required no Mg replacement with a mean Mg level of 2.22. This was significantly higher than the final 7 days on RCA (1.99; P = .00069). This case illustrates the challenges in maintaining Mg stores during CRRT. RCA is now the preferred method of circuit anticoagulation, with prolonged filter life and fewer bleeding complication compared to heparin circuits. Citrate inhibits coagulation within the circuit by chelating ionized calcium (Ca2+). Free Ca2+ and Ca-citrate complexes diffuse across the hemofilter with a percentual calcium loss as high as 70%, requiring continuous post-filter infusions of calcium to prevent systemic hypocalcemia. Magnesium loss during CRRT is also significant and may approach 15% to 20% of the total body pool within a week. Citrate chelates Mg with percentual losses comparable to calcium. Twenty-two CRRT patients on RCA had median losses >6 g/day. Doubling the Mg content in the dialyzate of 45 CRRT patients significantly improved Mg balance, but with the potential risk of increased citrate toxicity. A major obstacle to replacing Magnesium loss with the same precision as calcium is few hospitals can measure ionized Mg++ levels and must rely on total magnesium levels to guide replacement, despite a literature showing poor correlation with total body stores. Post-circuit continuous replacement of magnesium, as with calcium, in the absence of ionized magnesium levels would likely be very inexact and arduous. Being aware of the losses that can occur with CRRT, especially with RCA, and adjusting magnesium replacement empirically on rounds may be the only pragmatic action plan for this clinical issue.

Clinical features and acute management in adults

COVID-19 is a multisystem disease that requires holistic management. Most patients will experience mild symptoms including cough, fever and mild dyspnoea. A small proportion of patients will have severe manifestations including respiratory failure, ARDS and multiorgan failure. Extrapulmonary features are common and include gastrointestinal, thromboembolic, neurological, cardiac, renal, endocrine and dermatological manifestations. The care of COVID-19 patients requires close attention to these features. This includes respiratory support (such as supplemental oxygen, NIV and awake proning);fluid, electrolyte and nutrition management;prevention, detection and treatment of thrombotic events;management of diabetic complications;review of medications;appropriate use of antibiotics;and evidence-based use of therapeutic agents such as corticosteroids, antivirals such as remdesivir and other emerging therapies such as immunomodulating agents. Early planning for treatment escalation and decision making around the appropriateness of cardiopulmonary resuscitation are crucial as deterioration can be rapid. Prolonged symptoms occur in a minority of patients and longitudinal follow-up is required.Copyright © ERS 2021.

Initiating Home Parenteral Nutrition Therapy in a Patient at High Risk of Refeeding Syndrome After COVID-19 Infection

Background: An emerging finding about COVID-19 is its effect on nutrition and weight loss. The COVID-19 symptoms of fatigue, altered taste or smell, and lack of appetite are well known. But COVID-19 may have a more profound effect on clinical nutrition status. Two recent studies have identified that approximately one-third of ambulatory COVID-19 patients are at risk of experiencing weight loss >= 5% (Anker, et al;di Filippo, et al). The case study presented here discusses home start total parenteral nutrition (TPN) in a patient recently diagnosed with COVID-19 at high risk for refeeding syndrome. Method(s): N/A Results: Case Study: A 92-year-old patient was diagnosed with COVID-19 on June 8, 2022. Over the next week, she was hospitalized twice to manage symptoms of acute mental status changes, lethargy, aphasia, hypotension, and loss of appetite. The patient received nirmatrelvir/ritonavir, remdesivir, and bebtelovimab to treat COVID-19 at different times between June 9, 2022, and June 18, 2022. She remained COVID positive and continued to deteriorate clinically. On June 20, 2022, the patient began receiving 24/7 homecare, including intravenous (IV) fluids of dextrose 5% in normal saline (D5NS) 1000 mL daily for three days. She continued to experience loss of appetite and had no bowel movement for 3 days. On June 23, 2022, she was referred to this specialty infusion provider to initiate TPN therapy in the home setting. The patient's BMI was 18.2 kg/m2. Lab results revealed potassium 3.0 mmol/L, phosphate 1.6 mg/dL, and magnesium 1.6 mg/dL. High risk of refeeding syndrome was identified by the level of hypophosphatemia and hypokalemia. The specialty infusion provider's registered dietitian recommended to discontinue D5NS and begin NS with added potassium, phosphate, and magnesium. Thiamine 200mg daily was added to prevent Wernicke's encephalopathy. The patient's clinical status and lab values were monitored closely each day until her electrolyte levels stabilized (Table 1). Home TPN therapy was initiated on June 28, 2022, with <10% dextrose and 50% calorie requirement with 85% protein and 1.0 g/kg lipids. Three-day calorie count and nutrition education were performed four days post TPN initiation. Oral intake met only 25% of estimated needs. Over several days, theTPN formula was gradually increased to goal calories and the infusion cycle was slowly decreased. The following week, the patient's oral intake improved to 60%-75% of estimated needs. Her constipation resolved, and she showed improvement in functional status and mobility. Her appetite drastically improved when the TPN was cycled. Another three-day calorie count was performed when TPN calories reached goals. Oral intake demonstrated 100% estimated calorie and protein needs. TPN therapy was ultimately discontinued on July 14, 2022. As of September 30, 2022, the patient has stabilized at her pre-COVID weight of 45 kg with full recovery of appetite, function, and cognition. Discussion(s): The ASPEN Consensus Recommendations for Refeeding Syndrome (da Silva, et al) describe the repletion of electrolyte levels before introducing calories to prevent end-organ damage associated with refeeding syndrome (respiratory muscle dysfunction, decreased cardiac contractility, cardiac arrhythmias, and encephalopathy). Conclusion(s): This case study highlights the successful initiation of home TPN therapy in a patient at high risk of refeeding syndrome post COVID-19 infection. Although home start TPN and the risk of refeeding syndrome are not new concepts, they must be considered in the setting of COVID-19. Given the effects COVID-19 has on taste, smell, and appetite and the recent finding that one-third of patients with COVID infection may experience weight loss of >= 5%, nutrition support and patient education are vital components of overall patient care. (Figure Presented).

Outcomes, Risk Factors, and Incidence of Acute Kidney Injury in Hospitalized COVID-19 Patients

Background: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) is the virus causing Coronavirus Disease 2019 (COVID19). Apart from respiratory disease, this virus can affect different organs. Objectives: Therefore, multiple mechanisms have been hypothesized for Acute Kidney Injury (AKI) in COVID-19. In this study, we evaluate the incidence and prognosis of AKI in COVID-19 patients. Methods: This retrospective cohort study assessed 397 COVID-19 patients hospitalized between April 1, 2020, and September 30, 2021. Patients with a sudden rise of serum creatinine level, more than 0.3 mg/dl in two days or more than 50% of the initial level in one week, were diagnosed with AKI. Demographic, laboratory, and clinical features were compared in AKI patients with patients without AKI. Results: A total of 397 patients with a mean age +/- standard deviation of 55.42 +/- 15.26 years were included in the study. According to diagnostic criteria, 48 (12.1%) patients developed AKI. Old age, a history of hypertension, and chronic renal failure were suggested as risk factors for AKI. High levels of C-Reactive Protein, Erythrocyte Sedimentation Rate, Lactate Dehydrogenase, D-dimer, and serum phosphorus upon arrival were also associated with an increased risk of AKI. In addition, the incidence of hypernatremia and hyperkalemia increased mortality in patients with AKI. Conclusion: The incidence of AKI in admitted COVID-19 patients affects the duration of hospitalization, the chance of ICU admission, and mortality. It is important to limit the use of nephrotoxic drugs and to maintain water-electrolyte balance to prevent the incidence of AKI and improve the outcome.

An Immunocompetent Adult With Adenovirus Hepatitis

Introduction: In the US there has been a recent outbreak of adenovirus hepatitis in the pediatric population. However, to our knowledge, there has been only one reported case of adenovirus hepatitis in an immunocompetent adult. We have identified another such case. Case Description/Methods: A 25 year old female with no medical history presented with abdominal pain, nausea, vomiting, diarrhea, and subjective fevers for two weeks and was found to have transaminitis 25-30x the upper limit of normal, which were: AST 791, ALT 542, ALP 92, and total bilirubin of 2.9. The patient reported no prior history of liver disease. She denied alcohol, tobacco, illicit drugs, or herbal medications, but did report taking acetaminophen 1500 mg daily for two weeks. Serum acetaminophen levels were normal and serum and urine toxicology were negative. US with doppler was unremarkable, CT showed cholelithiasis, MRCP showed a normal common bile duct without obstructive calculus. Autoimmune causes of hepatitis, ceruloplasmin and alpha-1 antitrypsin were all unremarkable. HAV, HBV, HCV, HDV, HEV, CMV, HSV, VZV, EBV, HIV, and COVID19 were all negative. Ultimately, the serology for adenovirus was positive. After a week of supportive treatment, the patient's labs trended down and symptoms resolved. Discussion(s): Adenovirus is confirmed by a rise in antibody titer or by virus detection. Coagulative necrosis in histopathology is a finding in liver biopsies if they are pursued in unexplained cases of liver injury. Ultimately, adenovirus hepatitis can be diagnosed once all common causes of hepatitis have been excluded. In the current outbreak, only children have been getting adenovirus hepatitis. In adults, a high prevalence of neutralizing antibodies contributes to immunity, and therefore only in immunocompromised states, do adults get such an infection. Supportive care with IV fluids, electrolyte correction, and antiemetics usually is enough with eventual symptomatic and laboratory improvement as it was for our patient. Studies have shown that extensive disease can be treated with antiviral drugs, cidofovir, and ribavirin. Our patient's history of acetaminophen use is a confounder, however, her normal serum level and her symptoms suggestive of an infectious cause made acetaminophen less of a culprit. We hypothesize that our patient's use of acetaminophen when she was initially exposed to the virus is what made her susceptible to developing adenovirus hepatitis and we hope this case adds insight for clinicians dealing with future adult cases.

What the Eye Cannot See: A Case of Persistent Altered Mental Status in a Patient With Cholestatic Liver Disease?

Introduction: Altered mental status (AMS) is a common symptom in patients with liver disease with a wide list of differential diagnoses. Knowledge of etiologies of AMS unique to patients with hepatic dysfunction is vital in order to help recognize, diagnose, and treat the underlying cause in a timely manner. Case Description/Methods: A 46-year-old man with a history of recent COVID infection was transferred to our hospital for further evaluation of acute liver injury and AMS. On arrival, his labs were notable for AST of 408 U/L, ALT of 620 U/L, ALP of 5942 U/L, TB of 11.0 mg/dL, and an INR of 1.1. His work-up included an MRCP that showed segmental biliary ductal dilation with associated restricted diffusion and peribiliary enhancement concerning for sclerosing cholangitis. ERCP revealed a 3cm biliary cast that was removed and noted diffuse rarefaction of ducts throughout the entire biliary tree. A liver biopsy revealed centrizonal cholestasis with portal-based bile ductular reaction and mild bile duct injury. Despite adequate treatment of suspected infection and hepatic encephalopathy, his AMS persisted. His basic metabolic panel (BMP) was notable for Na of 143 mEq/L. A send-out lipid panel that was obtained to work-up his dyslipidemia revealed a total cholesterol of 1018 mg/dL, triglycerides of 420mg/dL, and the presence of lipoprotein X. A venous blood gas (VBG) was obtained showing a Na of 157 mEq/L and serum osmolality was 322 mmol/kg, confirming true hypernatremia. He was slowly treated with hypotonic solutions with significant improvement in his mentation. On follow-up one year later, he has persistent cholestasis and is currently being considered for liver transplant. Discussion(s): The final diagnosis was COVID-related ischemic cholangitis and disappearing bile ducts with persistent cholangiopathy, presenting with severe cholestasis, accumulation of lipoprotein X, and pseudonormonatremia. When faced with severe cholestatic liver disease, clinicians should keep in mind the possibility of accumulation of lipoprotein X and its association with hyperviscosity and spurious electrolyte abnormalities. Clinicians should rely on obtaining blood gas analyses for accurate electrolyte measurement in such cholestatic patients as blood gas analyses utilize direct ion-sensitive electrodes (ISE) to measure electrolytes, whereas routine basic metabolic panels utilize indirect ISE that are liable to spurious results in the presence of hyperlipoproteinemia/lipoprotein X.

Rising level of pulmonary dioxin might trigger CMV and HSV-1 reactivation via bHLH/PAS/AhR:ARNT transcription pathway in lungs of immunocompetent COVID-19 patients with ARDS

Study objective. It has been shown that human common viruses are new target genes for host cell dioxin receptor transcriptional (AhR-ARNT) complex initially proven to up-regulate mammalian genes containing dioxin-response elements (DRE) in the promoters [doi:10.1016/j.ijid.2012.05.265]. Initially, transactivation of HIV-1 and HBV by 2,3,7,8-tetrachlodibenzop- dioxin (TCDD) at low nanomolar range was demonstrated [doi:10.3109/00498259309057034]. Noteworthy, transactivation of human cytomegalovirus (CMV) was shown with 0.3 ppt dioxin, i.e. lower than its current background level in the general population (~3.0 ppt). Recently, reactivation of CMV infection was found to influence worse clinical outcome following SARS-CoV-2 infection (doi: 10.1186/s12979-020- 00185-x). Other findings showed that CMV and herpes simplex virus 1 (HSV-1) reactivation were observed in immunocompetent patients with COVID-19 acute respiratory distress syndrome (ARDS) (doi.org/10.1186/s13054-020-03252-3). Addressing occurrence of Herpesviridae reactivation in severe COVID-19 patients, and still unspecified real triggers of CMV and HSV-1 reactivations, we tested TCDD, which current body burden (DBB) ranges from 20 pg/g (TEQ in fat) in general population to 100 pg/g in older people. Methods. In Silico quantitation of active DRE in promoters of viral genes. Virus DNA hybridization assay. Clinical and epidemiological analyses. Results and Discussion. In this study, a computational search for DRE in CMV and HSV-1 genes was performed by SITECON, a tool recognizing potentially active transcriptional factor binding sites. In silico analysis revealed in regulatory region of CMV IE genes from 5 to 10 DRE, and from 6 to 8 DRE in regulatory region of HSV-1 IE genes.We established that a low picomolar TCDD can trigger up-regulation of CMV and HSV-1 genes via AhR:Arnt transcription factor in macrophage(doi.org/10.1016/ j.ijid.2012.05.265) and glial human cell lines (doi.org/10.1016/j. jalz.2016.06.1268), respectively. In fact, viral reactivation may be triggered in COVID-19 ARDS patients by higher pulmonary TCDD concentrations, because "lipid storm" within lungs of severe COVID-19 patients has been recently reported (doi.org/ 10.1101/2020.12.04.20242115). TCDD is known as the most potent xenobiotic, which bioaccumulates and has estimation half-life in humans of up to 10 yr. Due to hydrophobic character (Log P octanol/water: 7.05), TCDD partitions into inflammatory lipids in lung tissue thus augmenting its local concentration. Population-based epidemiological data on SARS-CoV-2 first wave of pandemic revealed high level of CMV seropositivity and cumulative mortality rate 4.5 times in Lombardi region of Italy, where after Seveso industrial accident TCDD plasma level in pre-exposed subjects is 15 times the level in rest of Italy (doi. org/10.3389/fpubh.2020.620416). Also, Arctic Native (AN) peoples consume dioxin-contaminated fat in seafood and have TCDD DBB, i.e. 7 times that in general population. To the point of this paper, their COVID-19 mortality is 2.2 times of that among non-AN Alaskans (doi: 10.15585/mmwr.mm6949a3). Conclusion(s): TCDD in the picomolar range may trigger CMV expression in lung cells and commit virus to the lytic cycle, which can be applied to reactivation of Herpesviridae infection in immunocompetent patients with COVID-19 ARDS syndrome.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Severe Acute Hepatitis: An Emerging Grave Illness in Children

Acute hepatitis of unknown origin in children has been recently described in the literature, and a case definition has also been proposed for this condition. The exact etiology is unknown and exclusion of infectious, metabolic, autoimmune and toxin mediated injuries is essential. Management for this condition is supportive, but some may require liver transplantation. Infection prevention and control practices are important as the etiology remains unidentified.Copyright © 2023, Indian Academy of Pediatrics.

Diazoxide in the Treatment of Asymptomatic Refractory Hypoglycemia in End Stage Renal Disease

Introduction: Diabetic patients with end-stage renal disease (ESRD) treated with insulin or any other diabetic agent show high variations in their glucose metabolism, lower insulin clearance level, and uncertain accuracy of glycemic control measurements. Therefore, these patients are at a greater risk of developing hypoglycemia. Diazoxide use in the treatment of spontaneous and refractory hypoglycemia in this population has not been well documented. We report a case of a young diabetic male that has been successfully treated with diazoxide for his asymptomatic refractory hypoglycemic episodes. Case Description: A young man with type 2 diabetes mellitus complicated by diabetic nephropathy, on hemodialysis for ESRD, presented with shortness of breath due to COVID pneumonia. After resolution of his infection, he was noted to have recurrent asymptomatic hypoglycemic episodes, although he has been off his diabetes medications for the past few years due to worsening of his kidney function. His oral intake was adequate and there was no concern for malnutrition, or any substance use. From the testing performed, we were able to exclude exogenous insulin or insulin secretagogues use and the presence of insulin antibodies. Insulin and noninsulin (insulin-like growth factor) mediated mechanisms were also ruled out. Since he was having recurrent and refractory asymptomatic hypoglycemic episodes and to minimize the need for supplemental dextrose containing fluids, he was started on diazoxide at 3 mg/kg/day. Knowing the risk of fluid retention with diazoxide, this patient on hemodialysis tolerated it well. Diazoxide helped reduce his episodes of hypoglycemia and he was then safely discharged on it. Discussion(s): In ESRD, hypoglycemia can be explained by the impaired contribution of the kidneys to gluconeogenesis and glucose release, as well as the higher insulin levels caused by insulin resistance and decrease in insulin clearance. When his hypoglycemia persisted even after the resolution of his infection, further testing and work-up was done and other causes of hypoglycemia were ruled out. Generally, diazoxide is used as a treatment to manage the symptoms of hypoglycemia in congenital hyperinsulinism, insulinomas and post bariatric surgery cases of hyperinsulinemic hypoglycemia. However, it has not been the optimal treatment when it comes to treating hypoglycemia in ESRD patients because of its side effects;specifically, fluid retention, and electrolyte imbalances. In our case, the patient was treated with diazoxide as a last resort, despite its known side effects and the limited documentation of its use in ESRD patients. Actually, a few other case reports, have also shown promising results with the use of diazoxide for that purpose with no or minimal side effects. However, there are not enough studies that have shown the benefits or risks of long-term treatment of diazoxide in ESRD patients, an area of growing interest.Copyright © 2023

To study the characterization of the CT Brain in COVID 19

Aim: To study the characterization of the CT Brain in COVID 19. Material(s) and Method(s): Patients of COVID 19 who had neurological signs either before they were admitted or while they were in the hospital had a CT brain plain once during their time in the hospital. CT Brain plain presentations were shown to correspond with CNS symptoms, progression throughout the patients' hospital stays, and outcomes. Several tests, such as RT-PCR for COVID 19, CT Brain plain, complete blood count, liver function tests, renal function tests with electrolytes, and others were performed. Result(s): In the current investigation, there were a total of 50 patients, 46 (92%) of whom were male, while just 4 (8%), on the other hand, were female. The patients' ages ranged anywhere from 35 to 82 years old, with a mean of 65.85+/-8.69 years. NLR was 14.98+/-2.69 (range 1.31-47.5), mean LDH 992.17+/-25.69 (range 221-5125), and Hs-CRP was 171.22+/-22.69 (range 2.9-321.5). Mean haemoglobin of the patients was 11.12+/-1.85 (range 4-15 g/dl), total leukocyte count was 16580.63+/-5896.45, mean platelet count was 2.11+/-1.02 / lacs (0. 27 patients, or 54%, were discovered to have had an ischemic stroke, whereas 5 patients, or 10%, were found to have had a hemorrhagic stroke. The CT brain results were found to be abnormal in 30 individuals (or 60%), whereas in 20 patients (or 40%), they were determined to be normal. 11 (22%) of the patients required the assistance of a ventilator, 6 (12%), of the patients used a BiPAP, 2 (4%), of the patients used a Hudson mask, and 10 (20%) of the patients had NRM. Conclusion(s): In conclusion, we were surprised to find that the proportion of patients with severe COVID-19 infection who had abnormal brain CT scans was rather significant. Ischemic stroke was the most common kind of stroke that occurred in conjunction with aberrant CT results. We believe that the connection between aberrant brain CT and the fate of patients warrants further validation in a wider patient population.Copyright ©2022Int. J. Life Sci. Biotechnol. Pharma. Res.

Successful matched unrelated donor hematopoietic stem cell transplantation for infantile Wolman disease

Introduction: Wolman disease is a rare genetic disorder with an autosomal recessive inheritance. A mutation in the LIPA gene causes lysosomal acid lipase (LAL) deficiency results in lipid storage and adrenal insufficiency. Death in early infancy is due to liver failure. Patients and methods: We describe the clinical course of a three-month-old infant diagnosed with Wolman disease. A rapid mutational analysis confirmed a LIPA gene defect. Results: He underwent matched unrelated donor peripheral blood stem cell hematopoietic stem cell transplantation (HSCT) at 3 months of age, with a treosulfan-based conditioning, which resulted in engraftment with donor-derived hematopoietic cells. He required supportive care for sinusoidal obstruction syndrome and mucositis. He was administered low dose prednisolone for grade I skin graft versus host disease, and a complete donor chimerism was documented on several occasions. At one year post HSCT, his growth and development were optimal, and there was no hepatosplenomegaly. He is maintained on glucocorticoid and mineralocorticoid supplements for primary hypoaldosteronism. Conclusion: The case emphasizes the timely diagnosis and the potential for successful treatment of Wolman disease by HSCT. © 2022 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics

West Nile Meningoencephalitis in a Patient with Leiomyosarcoma Presenting with Neutropenic Fever

Case Report: West Nile Virus (WNV) was first isolated from the West Nile district of Northern Uganda in 1937, but was first detected in the United States well over half a century later in 1999. The arthropod-borne virus has since persisted, with 2,401 cases reported to the CDC on average annually. The infection typically causes a nonspecific acute systemic febrile illness with occasional gastrointestinal and skin manifestations;however, in less than 1% of infected patients, it can cause severe and potentially fatal neuroinvasive disease, presenting as meningitis, encephalitis or acute flaccid paralysis. Immunosuppression is one of the risk factors associated with the development of neuroinvasive disease, and chemotherapy thus places patients at risk. Uterine leiomyosarcoma is a rare gynecological malignancy. Palliative chemotherapy is common in late stage disease, but may predispose patients to conditions that present as neutropenic fever, leading to a diagnostic conundrum. This is the first case report where patient with neutropenic fever was found to have West Nile neuroinvasive disease, so it is important to include West Nile disease in the differential diagnosis. Case Description: This is a case of a 45-year-old female with history of diabetes, hypothyroidism and recently diagnosed uterine leiomyosarcoma status post tumor debulking with metastasis on palliative chemotherapy with gemcitabine that presented to the Emergency Room for a fever of 103.8 degrees Fahrenheit. Given the history of advanced leiomyosarcoma, the patient was admitted for neutropenic fever with an absolute neutrophil count of 1000. During the hospitalization, the patient became acutely altered and confused. CT head without contrast and lumbar puncture were performed. Due to clinical suspicion of meningitis, she was started on broad spectrum antibiotics. Lumbar puncture revealed leukocytosis of 168 with lymphocytic predominance and elevated protein level in the cerebrospinal fluid, therefore acyclovir was started due to high suspicion of viral meningoencephalitis. An EEG showed severe diffuse encephalopathy as the patient was persistently altered. A broad workup of infectious etiology was considered including HIV, syphilis, hepatitis A, B, C, COVID-19, adenovirus, pertussis, influenza, WNV, HHV6, coccidiomycosis, aspergillus, and tuberculosis. Patient was ultimately found to have elevated IgM and IgG titers for West Nile Virus. Discussion(s): It is important to consider a broad spectrum of diagnosis in patients with metastatic carcinoma presenting with new-onset fever and acute encephalopathy. This includes working up for other causes of altered mental status including cardiac, neurologic, psychiatric, endocrine, metabolic, electrolyte, drug, and infectious etiology. While uncommon in the healthy population, WNV encephalitis should be on the radar for any patient who is immunocompromised or on immunosuppressive therapy, especially those who present with a neutropenic fever.

Drug Interaction between Paxlovid and Tacrolimus in an Adolescent with Inflammatory Bowel Disease

The coronavirus disease of 2019 (COVID-19) caused by SARS-CoV-2 virus led to a worldwide pandemic. Emergency use of an investigational medication, Paxlovid, was approved for patient 12 and older who tested positive for COVID-19 and at high risk for severe infection. Inflammatory Bowel Disease (IBD) is a chronic condition causing inflammation in the gastrointestinal tract. Ulcerative Colitis (UC) is a type of IBD centralized in colon and commonly treated with Immunosuppressive drugs. We present an adolescent with UC treated with paxlovid due to being on tacrolimus who developed with suspected tacrolimus toxicity. CASE REPORT: A 13-year-old female with UC presented to the ED with vomiting and fatigue after paxlovid ttreatment for COVID. The patient's UC treatment included tacrolimus along with ustekinumab. She had been diagnosed with SARS-CoV-2 and prescribed Paxlovid bid x 5 days due to immunosuppressive status. Tacrolimus was held during treatment. Once paxlovid completed, tacrolimus was restarted. Two days later, patient presented to ER for vomiting, fatigue, headaches and myalgia. Labs revealed a tacrolimus level of >60 ng/ml. Electrolytes and Creatinine were normal. Toxicology felt this was due to interaction between paxlovid and tacrolimus. Patient advised to hold tacrolimus for 48 hours and repeat levels were 15.8 ng/mL. Symptoms resolved and level repeated three days later and was 2.9 ng/mL. DISCUSSION: Tacrolimus is an immunosuppressant, commonly used for management of organ transplants but also been found effective in treatment of IBD. Tacrolimus requires close monitoring as toxicity may lead to acute or chronic kidney disease. The normal concentration is between 5-15 ng/mL. Due to rapid escalation of the COVID-19 pandemic, Paxlovid was approved for emergency use for treatment of high-risk patients. It is administered as a 5-day oral course consisting of nirmatrelvir and ritonavir. Our patient was prescribed Paxlovid due to risk secondary to immunosuppression. She was appropriately instructed to stop tacrolimus. Ritonavir is a cytochrome P450 3A inhibitor and can increase plasma concentration of tacrolimus. She restarted tacrolimus treatment 12 hours after her last dose of Paxlovid and presented with symptoms and a level consistent with toxicity. This level was concluded to be due to drug interaction between tacrolimus and Paxlovid. After further withholding of tacrolimus, symptoms improved, and levels normalized. Previous reports in transplant population stress importance of decreasing the dose of tacrolimus or withholding during the course of paxlovid treatment. This case demonstrates the importance of not only ceasing tacrolimus when administering paxlovid, but continuing discontinuation for longer period post completion of therapy to minimize interactions.Copyright © 2023

Mechanisms of Atrial Fibrillation in Covid-19

Atrial fibrillation (AF) is the most frequent form of cardiac arrhythmia in COVID-19 infected patients. The occurrence of AF paroxysms is often associated with the acute period of infection in time. At the same time, the pathophysiological mechanisms of the occurrence of AF associated with COVID-19 remain insufficiently studied. The review considers the available literature data on the influence of factors such as reduced availability of angiotensin-converting enzyme 2 receptors, interaction of the virus with the cluster of differentiation 147 and sialic acid, increased inflammatory signaling, "cytokine storm", direct viral damage to the endothelium, electrolyte and acid-alkaline balance in the acute phase of severe illness and increased sympathetic activity.Copyright © Autors 2023.

Comparative Study of Serum Electrolytes in Covid-19 and Healthy Patients in Tertiary Care Center, Karimnagar

Introduction- Electrolyte balance of the body is maintained by renin angiotensin aldosterone system. Some previous studies suggested that COVID-19 is associated with gastrointestinal symptoms, such as diarrhea and vomiting. This may results in electrolyte disturbances in patients. Electrolytes in body like sodium (Na), potassium (K). Chloride (Cl) plays an important physiological role in maintaining acid base and water balance of cells of the body. Aims and objectives: Our study aimed to compare some electrolyte between covid 19 and non-covid patients retrospectively. Material(s) and Method(s): This retrospective study included total 57 males and 43 females in the age group of 28 to 65 years. The results were compared with 100 age and sex matched healthy controls. Estimation of serum electrolytes was done with the collected venous blood samples using the ion selective electrode technique in an electrolyte analyzer. Analysis was done using SPSS V 25 Software. Chi-square and t-test were used to see association and difference between two variable respectively. Result(s): We have found that covid 19 is associated with low levels of electrolytes like Na, K, Cl. Chloride levels in both the groups was not statistically significant. But Hyponatremia and Hypokalemia were observed in cases group with high statical Signficance. Conclusion(s): Study found that electrolytes deterioration in these patients play a critical role in patients management. Thus a monitoring of electrolyte is essential throughout their illness to manage covid patients to improve their quality of life.Copyright © 2020 Ubiquity Press. All rights reserved.

Massive polyuria associated with severe COVID-19-related pneumonia complicated by pulmonary embolism

Coronavirus disease 2019 (COVID-19) predominantly manifests with signs of respiratory system injury;however, multi-systemic manifestations may occur. Renal pathology develops in up to 80% of patients with COVID-19. The aim of the study was to describe the case of isolated massive polyuria of unknown etiology in the patient with severe COVID-19-related pneumonia complicated by pulmonary embolism (PE). A 54-year-old male with bilateral pneumonia, related to COVID-19, developed PE. The next day after successful thrombolysis with alteplase (90 mg) the diuresis of the patient began to increase and fluctuated between 5000 mL and 8000 mL. The diuresis returned to normal ranges two weeks after PE episode. The rise of the diuresis was not accompanied by electrolyte disorders and elevation of serum creatinine. Changes in the urine tests were minimal, only once the urine protein was detected (0.25 g/L). The highest urine excretion was observed in evening hours (16.00-24.00). Chest CT on the day 14 after the patient's admission revealed 90% of lung tissue injury, cranial CT showed no brain abnormalities, including hypothalamus and pituitary gland. The patient's condition met neither diagnostic criteria of acute kidney injury, nor acute interstitial nephritis, nor pituitary gland damage. The course of the polyuria in the presented case was benign (self-limiting, no blood electrolyte abnormalities, compensated by oral rehydration only). Polyuria in patients with COVID-19 may not be a life-threatening condition that does not require active treatment.Copyright © 2021 EDIZIONI MINERVA MEDICA.

Novel Coronavirus is the Only Virus Causing Childhood Invasive Diarrhea: A Case Series

Introduction: Typical manifestations of Coronavirus disease 2019 (COVID-19) include respiratory involvement. Gastrointestinal (GI) symptoms have also been reported as early clinical manifestations. The GI involvement can represent with diarrhea, vomiting, and abdominal pain. The present research aimed to identify dysentery as one of the signs of GI involvement in the novel coronavirus infection in children. Case Presentation: We report twelve patients with COVID-19 and dysentery. All these children had positive reverse transcriptionpolymerase chain reaction (RT-PCR) results. None had underlying illnesses or recent travel history. However, all children had contact with a first-degree relative affected by non-digestive COVID-19. In three patients, obvious dysentery was observed, and in the rest, red and white blood cells were evident in the stool exam. Stool exams were negative for bacterial infections, parasites, and the toxin of Clostridium difficile. Abdominal ultrasonography and echocardiographic evaluations to rule out multisystem inflammatory syndrome in children were normal. Supportive treatment, such as zinc supplementation and probiotics, was prescribed. They also received intravenous fluid therapy based on their dehydration percentage. In the end, they were discharged in good general condition without any complications. No GI complications were found in the follow-up series. Conclusion(s): Dysentery in children can be one of the GI manifestations of COVID-19, which is usually self-limiting. It does not require invasive diagnostic measures and antiviral treatments. This symptom is in contrast to other viral infections of the GI tract.Copyright © 2022, Author(s).