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

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

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.

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).

Liposomal amphotericin associated nephrotoxicity in patients with Mucormycosis: An epidemic in the midst of Pandemic

Introduction: Following second wave of COVID 19 infection in India there has been unprecedented spike in mucormycosis cases. Liposomal amphotericin(LAmB) is the drug of choice in most of these cases. Though nephrotoxicity of conventional amphotericin has been well described in literature, there is sparse data on nephrotoxicity following of LAmB use.Herein we describe spectrum of kidney disease and electrolyte abnormalities that arised following LAmB use in patients afflicted with mucormycosis. Method(s): It is a single centre retrospective observational study. Hospitalised patients with mucormycosis who were started on LamB and if they develop Acute Kidney Injury (AKI)criteria as per KDIGO2012 guidelines during hospital stay were included in the study after excluding patients with pre existing Chronic Kidney Diseases( CKD),concomitant use of other Nephrotoxic medications,use of nonLAmB formulations for mucormycosis treatment,AKI at the time of admission and critical illness requiring ICU stay.Their demographic characteristics,co morbidities,salient clinical examination findings and laboratory parameters were entered in excel sheet.Descriptive statistics were used to analyse data. Result(s): Mean Age of study population was 51.03 years. Male to female ratio was 25:6.Among comorbidities, Diabetes was seen in 74.19% cases, Hypertension was seen in 35.4% and Ischemic Heart disease was seen 9.6% cases. When risk factors for mucormycosis were analysed 100% of study population had recent COVID19 infection, 93.5% of study population had prior steroid use and 9.6% of the patients had received Tocilizumab. Out of 102 patients who received LAmB 31(30.3%) developed AKI. Among these cases, Stage1 AKI was seen in 8 (25.8 %) cases,Stage 2 AKI was seen in 17 (54.8%) cases and Stage3 AKI was seen in 6 (19.3%) cases. None of these patients had oliguria or requirement of dialysis during hospital stay. 54.8% of patients had persistent AKI at the time of discharge.Hypokalemia was seen in 77.4% cases and 41.9% had severe hypokalemia requiring IV potassium treatment.Hyponatremia was seen in 51.6% cases, most of these cases were mild and only one patient had severe hyponatremia requiring hypertonic saline infusion.Hypomagnesemia was seen in 29 % cases. Conclusion(s): LAmB was associated with significant nephrotoxicity resulting in development of AKI in 30% of cases.Most of these cases had stage 2 AKI and none of them required dialysis support.Almost half of the study population had persistent AKI at the time of discharge.Among the electrolyte disorders,Hypokalemia was particularly severe. No conflict of interestCopyright © 2023

Longitudinal analysis of electrolyte prolife in intensive care COVID-19 patients

Introduction: According to a substantial body of research, electrolyte abnormalities are a common manifestation in coronavirus disease 2019 (COVID-19) patients and are associated with adverse outcomes. This study aimed to investigate electrolyte imbalances in COVID-19 patients and assess their relation to mortality. Method(s): Adult COVID-19 patients hospitalized in the Security Forces Hospital in Saudi Arabia from June 8th till August 18th, 2020 were enrolled in this retrospective observational study. We examined baseline characteristics, comorbidities, acute organ injuries, medications, and electrolyte levels including sodium, potassium, chloride, calcium, bicarbonate, phosphate, and magnesium on ICU admission, as well as every following day of ICU stay, until death or discharge. Patients were stratified according to survival, and differences in variables between groups were compared using Mann-Whitney's U test or Fisher's exact test. Longitudinal electrolyte profiles were modeled using random intercept linear regression models. Result(s): A total of 60 COVID-19 patients were enrolled. Compared to survivors, non-survivors had significantly higher sodium and phosphate on admission and death, higher potassium and magnesium at death, and significantly lower calcium at death. Abnormalities in admission levels of chloride and bicarbonate were also more frequently observed in non-survivors. Furthermore, in the deceased group, we observed a daily increase in potassium and phosphate levels, and a daily decrease in sodium and chloride. Finally, calcium increased in non-survivors over time, however, not as significantly as in the survivor group. Conclusion(s): Admission levels of electrolytes and changes over the course of ICU stay appear to be associated with mortality in COVID-19 patients.Copyright © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Liquorice-induced pseudohyperaldosteronism: The importance of dietary intake in the differential diagnosis of hypokalaemia, a case report

Introduction : Hypokalaemia is a common electrolyte disorder and mild imbalances are frequently found in routine outpatient blood testing. However, severe potassium deficiency (<2,5 mmol/L) is rare and could provide a diagnostic challenge for clinicians. This report describes a case of hypokalaemia due to pseudohyperaldosteronism caused by the ingestion of liquorice, and demonstrates the importance of dietary intake assessment in hypokalaemia patients. Case presentation : A 45-year-old female without a notable medical history was admitted to the hospital with severe hypokalaemia (2.3 mmol/L) on laboratory testing. Two years earlier, her serum potassium level was adequate (3.8 mmol/L). She denied diarrhea and her only complaint was fatigue. Save for oral contraceptives, she reported no use of medications. On examination, she appeared malnourished and had high blood pressures. Although dietary intake was not evaluated at the time of presentation, it was eventually discovered she consumed liquorice daily since childhood. Furthermore, she tested positive for COVID-19 and had low serum magnesium and phosphate levels as well. Urine potassium excretion was never measured. Intravenous potassium phosphate was administered in high doses, in addition to magnesium supplementation and spironolactone, with eventual correction of the hypokalaemia and resolution of hypertension. The patient was advised to refrain from further liquorice consumption. Discussion : This case of hypokalaemia is thought to be induced by excessive liquorice ingestion, which can cause pseudohyperaldosteronism by inhibiting the conversion of cortisol to cortisone, thus increasing the cortisol levels which bind the mineralocorticoid receptor similarly to aldosterone, subsequently activating the renin-angiotensin-aldosterone system (RAAS) and causing features of mineralocorticoid excess, including hypokalaemia and hypertension. This patient also presented with aggravating factors. First, a magnesium deficit, which is known to impair potassium reabsorption across the renal tubules. Therefore, magnesium should be replaced to facilitate potassium correction, especially in hypokalaemia refractory to supplementation, as was done here. Second, concomittant COVID-19 infection could have contributed to the severity of hypokalaemia in this patient, as COVID-19 is thought to downregulate ACE2 expression, consequentially increasing angiotensin II, which will augment the potassium excretion in the urine. In conclusion, dietary preferences and nutritional status should be assessed in all patients presenting with hypokalaemia, as this could provide important clues for differential diagnosis and etiology of hypokalaemia. In this patient, electrolyte imbalances caused by malnutrition, and concomitant COVID-19 infection could explain why her liquorice consumption only now proved to be problematic after years of excessive intake.

SARS-CoV-2 S Protein Is a Competitive Inhibitor of Furin Mediated ENaC Activation

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 (Coronavirus disease 19). SARS-CoV-2 causes a multisystemic infection, which frequently presents with pulmonary oedema, endothelial damage and electrolytic abnormalities. An essential physiopathological feature of SARSCoV-2 involves cleavage of its S protein by furin or furin-like enzymes. It has been shown by sequence-based evidence that the S protein polybasic aminoacid sequence is identical to the consensus sequence for furin cleavage present in the human alpha subunit of the epithelial sodium channel (ENaC). Furin and furin-like enzymes are also involved in the posttranslational regulation of ENaC in many tissues, including the lung, endothelium, and the kidney, where cleavage is associated with increased activity of the channel. ENaC is involved in the regulation of fluid clearance, Na+, K+ and acid-base homeostasis, and endothelial function. Thus, we hypothesized that the S protein competes with ENaC for furin-mediated cleavage and activation. Method(s): We injected synthetic mRNA encoding WT S protein and mutant S protein lacking the furin consensus sequence (DELTA-Spike) into X. laevis oocytes with alphabetagamma-ENaC subunits. We then performed whole-cell voltage-clamp experiments and protein analysis by western blot. Result(s): We observed an interdependent competitive effect on the cleavage of both the S protein and ENaC when co-expressed, which was partially prevented with the injection of DELTA-Spike. We also found a decrease in the amiloride-sensitive sodium current in oocytes injected with the WT S protein but not with DELTA-Spike. This suggests diminished function of ENaC in the presence of WT S protein that depends on its furin cleavage site. Conclusion(s): These findings show evidence of a competitive interaction between the S protein and ENaC for furin-like enzymes. This suggests that SARS-CoV-2 infection may impair ENaC activity in human epithelia, which gives a plausible explanation to pulmonary oedema, endothelial damage, and electrolyte disturbances in patients with COVID-19.

Electrolyte Imbalance and COVID-19 Severity in Hospitalized Patients

Background: Various risk factors have been proposed for severe coronavirus disease 2019 (COVID-19);nonetheless, the prognostic role of serum electrolytes has not been widely studied. Objectives: The present study aimed to identify the potential prognostic role of electrolyte imbalance in hospitalized COVID-19 patients. Methods: This retrospective study was conducted in Imam Reza Hospital, Mashhad, Iran. The medical records of all COVID-19 patients admitted to the emergency department from May to August 2020 were evaluated. Demographic data and clinical findings upon admission were collected. Disease severity, lung involvement severity on imaging, inflammatory serum biomarkers, admission to the intensive care unit, and serum levels of sodium, potassium, magnesium, calcium (corrected by serum albumin level), and phosphorus were documented. Results: Most patients (60%) were male, and the mean age of the total population was 58.87 ± 1.82 years. Severe COVID-19 was detected in most cases (94.9%) who were significantly older (P = 0.037), had hypertension (P = 0.032), ischemic heart disease (P = 0.033), and higher serum urea (P = 0.001) and serum potassium (P < 0.001). Patients with poor prognosis based on computed tomography (CT) scores had significantly higher serum urea (P = 0.002) and magnesium (P = 0.035) than patients with good prognosis, while serum calcium was significantly higher in the latter group (P = 0.007). Furthermore, there was a significant relationship between COVID-19 severity and serum potassium (P < 0.001). Conclusions: Abnormal serum electrolytes are correlated with COVID-19 severity. Moreover, serum potassium level is a predictor of severe disease.

Rhabdomyolysis and Acute Myopathies

The clinical syndrome of rhabdomyolysis is based on the 'classical' triad of myalgia, weakness and pigmenturia. For this lecture it will be defined as an acute such clinical syndrome with markedly elevated serum CK. The common general triggers of rhabdomyolysis are: Exertion, heat & fever, fasting and dehydration, drugs and anesthesia and muscle trauma. The causes of rhabdomyolysis are divided to two general groups: Genetic (metabolic myopathies and dystrophies) and acquired. The main complications of rhabdomyolysis are acute kidney failure and electrolyte imbalance. There is no consensus on treatment guidelines but the main therapeutic modes are high fluid load (if renal status allows) and alkalization of urine. Initial observations on rhabdomyolysis and COVID-19 will be discussed. The lecture will present the issues with clinical cases and their dilemmas to enhance the relevance between the theory and clinical practice.

Description of Neutrophil-to-lymphocyte Ratio, C-reactive Protein, and Procalcitonin Levels in Pregnancy with COVID-19 at Sanglah General Hospital Period of April 2020–April 2021

Background: Theoretically, pregnant women are more susceptible to infection of coronavirus disease 2019 (COVID-19) and severe pneumonia due to presentation of physiological changes adaptation and immunosuppression during pregnancy. Based on the immune clock theory, if pregnant women had COVID-19 in the first and third it can appearance of cytokine storm due to hyperinflammation state, and lead to poor maternal and neonatal outcomes. Hyperinflammation state is characterized by an increase in inflammatory biomarkers in the serum, including the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and procalcitonin levels. This study aims to determine the characteristic of NLR, CRP, and procalcitonin in pregnancy with COVID-19 at Sanglah General Hospital, Denpasar, Bali, Indonesia. Methods: This study is a cross-sectional descriptive study using secondary data from patient’s medical records and is conducted in the delivery room and medical record department at Sanglah General Hospital, Denpasar from April 2020 to April 2021. Result: Pregnancy cases with COVID-19 in this study were in the 26–30-year age group, as much as 26 cases (37.14%) with most common comorbidities found were preeclampsia and electrolyte imbalance, as much as nine cases each (12.86%). Most of the neonates born at term, with birth weight 2,500 gm, and vigorous baby. The highest median NLR value was found in pregnant women with COVID-19 in comorbid with obesity, 6.79 (2.88–9.14). In this study, the cases with a length of stay more than or 10 days had a median NLR value of 6.93 (2.57–20.69), CRP 59.83 (1.60–151.56), and procalcitonin 0.145 (0.03–2.56), which are all higher than those whose length of stay was less than 10 days. Conclusion: NLR, CRP, and procalcitonin values are affected by the trimester of pregnancy, the maternal comorbidities, the commonly found chest X-ray features, the length of hospital stay, the prognostic value to be determined to find the disease severity, the needs of oxygen supplementation, and the intensive care treatment, and also they could be the predictors for neonatal outcome in pregnancy with COVID-19.

Thyroid storm in pregnancy: A case study

Introduction: Inadequately treated maternal hyperthyroidism increases the risk of severe preeclampsia, heart failure, and thyroid storm. Thyroid storm is a life-threatening endocrine emergency characterized by multiple organ failure due to severe thyrotoxicosis. A storm can be triggered by precipitating events such as trauma, surgery, infection, delivery;even pregnancy itself. Case Description: A 35-year-old lady presented to the emergency department with complete miscarriage. She had underlying hyperthyroidism for six years but defaulted her follow-ups and medications since the beginning of the Covid-19 pandemic. She complained of palpitations despite minimal vaginal blood loss. ECG showed sinus tachycardia with a heart rate of 190 beats per minute. Her hemoglobin level was stable, but thyroid function test showed hyperthyroidism with raised free T4 (60 pmol/L) and low TSH (< 0.01 mIU/L). Her Burch-Wartofsky score was 35, implying an impending thyroid storm. IV Verapamil was given immediately and her heart rate improved to 140-150 bpm. She was transferred to a high dependency ward for close monitoring and started on oral Propylthiouracil and Propranolol. Regrettably, when she began to improve, she requested for discharge against medical advice. Discussion: The diagnosis of thyroid storm is clinical, with laboratory tests consistent with overt hyperthyroidism. Clinical scoring systems such as the Burch-Wartofsky Score helps to confirm diagnosis and triage disease severity. Treatment is multimodal using medications (thioamides, iodide, beta-blockers, corticosteroids, antipyretics), oxygen, volume resuscitation, and correction of electrolyte imbalance. A high index of suspicion, rapid recognition, prompt treatment and intensive monitoring are key elements of management.

Critical care dietetic outcomes during the first wave of the COVID-19 pandemic

The COVID-19 pandemic led to a surge in patients being admitted to the Intensive Care Unit (ICU) and increased dietetic input was required for their daily nutritional management. Non-ICU dietitians were upskilled to meet this increased demand – resulting in an increase to 5 band 6 dietitians and 1 band 7 dietitian overseen by the band 8a clinical lead. The service also changed from a 5-day to a 7-day service. The aim of this service evaluation was to analyse changes in nutritional outcomes during the COVID-19 pandemic, and how changes to the dietetic service impacted upon dietetic outcomes. Outcomes included energy and protein provision, feed type used and prokinetic use. Data was collected for all ICU patients under dietetic care with a confirmed COVID-19 diagnosis for the period of 22/03/2020 to 04/06/2020 (75 days). Total patient cohort equalled 66. Patients were reviewed daily until the patient was discharged from ICU or the patient passed away. All data was then retrospectively analysed using descriptive statistics, and an independent t-test was used to compare COVID-19 feed delivery to previous feed deliverydata. Ethical approval was not required for this service evaluation. Of the 66 patients, 62 required enteral nutrition (EN). Feeding was commenced within 48 hours of ICU admission in 92% of patients. Average percentage feed delivery was 82.4% for energy and protein. This total does not include additional protein supplementation;therefore, the overall protein delivery was higher, with 36% of patients being prescribed 1 to 2 20g protein supplements per day. A total of 60% of patients were initially started on a fluid restricted feed for fluid balance or due to being proned. A total of 50% of patients continued with a fluid restricted feed, with 44% of patients receiving a standard protocol feed (1kcal/ml high-protein feed) and 6% receiving a peptide or renal feed. Prokinetics were required in 35% of patients. A total of 3% of patients (n=2) required parenteral nutrition due to persistent high gastric residual volumes despite prokinetics. Of the 66 patients, 46 (70%) were discharged alive from ICU. Of these, 70% were receiving total or supplementary EN at the time of discharge from the ICU. A number of barriers to maintaining high standards of patient outcomes arose at the onset of the COVID-19 pandemic. These included disruptions to normal MDT working, challenges in undertaking face-to-face assessments and reviews, and an increased caseload and footfall - thereby increasing the demand for ICU trained dietitians. Despite these barriers, this service evaluation demonstrates that percentage feed delivery remained relatively stable when compared to the pre-COVID 2020 audit (n = 35) - 82.4% vs. 85% respectively. An independent-samples t-test was conducted to compare feed delivery in pre-COVID and COVID-19 samples. There was no significant difference in the scores for pre-COVID (M = 85%, SD = 13.4) and COVID (M = 82.4%, SD = 16.8) samples;t(180) = -0.81, p =.42. This is despite 36% of patients requiring proning during COVID vs. 0% pre-COVID, and increased gastrointestinal intolerance evidenced by 35% of patients requiring prokinetics vs. 29% pre-COVID. These factors eliminated the ability to utilise ‘catch-up’ feeding, which significantly improves feed delivery in normal circumstances. This suggests that changes in dietetic provision of service, including delivering a 7-day service, thereby allowing more prompt management of nutritional issues and improved access to dietetic expertise, facilitated the maintenance of the pre-existing high standards of nutritional care. Achieving this degree of feed delivery necessitated the use of a variety of different feeds – to manage tolerance, fluid volume, electrolyte imbalances and ensure nutritional adequacy. Adapting feeding regimens to best meet the patients need is a key role of the dietitian, and in the absence of dietetic input it is unlikely these feeding strategies would have been utilised. The COVID-19 pandemic presented new challenges and obstacles to eve y aspect of the healthcare sector;necessitating fast adaptations, novel methods of working and reinforcing the importance of multidisciplinary teams to guide patient care in the absence of evidence-based guidelines. This service evaluation demonstrates that forward-planning and the expansion of services in alignment with demand can assure that patient care need not be compromised, despite the unprecedented challenges and barriers presented by the COVID-19 pandemic.

THE BIG IMPACT OF SMALL CHANGES IN NARROW THERAPEUTIC INDEX DRUGS

CASE: An 84-year-old woman with atrial fibrillation on Digoxin presented with acute onset of confusion associated with a week history of abdominal pain, vomiting, and poor fluid intake. A few days prior, Amiodarone was added to her drug regimen which included Lasix. Additionally, she received the COVID-19 booster vaccine which led to a viral-like syndrome resulting in dehydration. The patient was afebrile, normotensive, but bradycardic. EKG showed a prolonged PR interval and scooped ST segments. Labs showed hyperkalemia, pre-renal acute kidney injury (AKI), and a Digoxin level of 4.3 ng/mL (therapeutic range: 0.8-2.0 ng/mL). Digoxin and Lasix were held and Digoxin antidote, Digibind, was administered with normalizing heart rate, potassium, and clinical improvement. IMPACT/DISCUSSION: Digoxin is used to slow conduction in atrial fibrillation and increase cardiac contractility in heart failure. It inhibits the membrane sodium-potassium-adenosine triphosphatase pump (Na/K ATPase), resulting in increased cytosolic calcium and subsequent cardiac contractility and automaticity. In turn, this can also cause premature ventricular contractions and tachycardia. In the carotid sinus, increased baroreceptor firing and subsequent increased vagal tone occurs which can cause bradycardia, atrioventricular blocks, hypotension, and GI symptoms. In skeletal muscle, hyperkalemia can result due to the abundance of Na/K ATPase pumps. Digoxin has a narrow therapeutic index with serum levels easily affected by many commonly prescribed drugs by way of decreasing renal clearance, inhibiting P-glycoprotein, and inducing secondary electrolyte disturbances. That said, drug dosing should be individualized with close monitoring to avoid potentially life-threatening effects that may result with even mildly increased digoxin levels. Acute toxicity manifests as non-specific GI, and neurologic symptoms (confusion, lethargy, visual changes), hyperkalemia, and brady or tachy-arrhythmias. Treatment is with digoxin specific fragment antigen binding (Fab) antibody, Digibind, which binds digoxin, inactivating it within 6-8 hours. Postadministration, digoxin serum testing cannot distinguish free verse bound drug;therefore, drug levels remain elevated for days to weeks until the FabDigoxin complex is excreted. In the case above, the viral-like-syndrome after the booster vaccine with subsequent AKI secondary to dehydration likely precipitated Digoxin toxicity. Accompanying drug interactions of diuretics causing dehydration and hypokalemia, P-glycoprotein inhibitors (Amiodarone, Verapamil, Diltiazem, Quinidine), and ACE inhibitors can further worsen renal clearance and culminate in Digoxin toxicity. CONCLUSION: Given Digoxin's narrow therapeutic index, small clinical changes such as post COVID-19 vaccine flu-like symptoms, dehydration, and medication changes can manifest drug toxicity. Therefore, attentive monitoring of accompanying comorbidities and drug interactions is imperative at preventing catastrophic toxic effects.

Case Series of Consultation-Liaison Patients with Anorexia Nervosa during the Pandemic

Introduction: Anorexia Nervosa (AN) is an eating disorder defined by an abnormally low body weight due to purging behaviors/food intake restrictions and distorted self-image. Coronavirus disease 2019 (COVID-19) has changed our environment due to social distancing, lockdown, and reduced access to regular mental health services. Reports indicate a negative impact of COVID-19 on mental health1, including patients with AN2. Our Consultation-Liaison service noticed an increase in new-onset AN cases and a worsening of established AN cases attributed to the environment created by COVID-19. Methods: PubMed literature review with keywords “COVID-19” and “AN.” Review of seven AN cases seen during the pandemic. Case series: Seven cases (COVID-19 negative) of worsening AN were seen by our Consultation-Liaison service between August 2020 and January 2021. Six cases were newly diagnosed, five cases presented severe dehydration, electrolyte imbalance, or bradycardia requiring inpatient stabilization, and five cases needed transfer to inpatient eating disorder units. The lack of structured activities and increased social media use leading to distorted self-image were found to be a trigger. Discussion: The impact of the Pandemic in AN can vary. The lack of structure, increased social media use, and reduced access to mental health services may increase AN incidence and worsening of symptoms3. However, a study reported a positive response to AN treatment during confinement4, possibly due to family dynamics5. It is important to note that patients with AN are a vulnerable population that requires greater support and monitoring to prevent worsening symptoms and long-term consequences. These observations suggest the need for further research to understand the impact of the pandemic on AN symptoms onset and severity. References: 1. Phillipou, A., et al. (2020). Eating and exercise behaviors in eating disorders and the general population during the COVID-19 pandemic in Australia: Initial results from the COLLATE project. The International journal of eating disorders, 53(7), 1158–1165. https://doi.org/10.1002/eat.23317 2. Termorshuizen, J. D., et al. (2020). Early impact of COVID-19 on individuals with self-reported eating disorders: A survey of ∼1,000 individuals in the United States and the Netherlands. The International journal of eating disorders, 53(11), 1780–1790. https://doi.org/10.1002/eat.23353 3. Branley-Bell, D., et al. (2020). Exploring the impact of the COVID-19 pandemic and UK lockdown on individuals with experience of eating disorders. Journal of eating disorders, 8, 44. https://doi.org/10.1186/s40337-020-00319-y 4. Fernández-Aranda, F., et al. (2020). COVID Isolation Eating Scale (CIES): Analysis of the impact of confinement in eating disorders and obesity-A collaborative international study. European eating disorders review: the journal of the Eating Disorders Association, 28(6), 871–883. https://doi.org/10.1002/erv.2784 5. Yaffa, S., et al. (2021). Treatment of eating disorders in adolescents during the COVID-19 pandemic: a case series. Journal of eating disorders, 9(1), 17. https://doi.org/10.1186/s40337-021-00374-z

Bradyarrhythmia Associated with Remdesivir and Covid-19 Pneumonia: A Pharmacovigilance Analysis: A

Background: Different arrhythmias have been reported in patients with COVID-19 due to the complication of the disease, and medications used in the management of COVID-19. Remdesivir was approved by FDA for the management of COVID-19 patients in October 2020. There are several case reports suggesting remdesivir causing bradyarrhythmia in COVID-19 patients. Objective: To increase the knowledge and awareness among healthcare professions (HCPs) about the risk of arrhythmias associated with the use of remdesivir. Methods: We used the FDA Adverse Events Reporting System (FAERS) database to find bradyarrhythmia as a reported adverse event (AE) due to remdesivir until October,2021. Total 6,504 events were reported, out of which 5,996 (92.2%) were reported by HCPs. These AEs were included and further analyzed. Results: Out of 5,996 AEs reported with remdesivir, total 537 (9.0%) events were bradyarrhythmia. There were 74 (1.27%) events reported for atrial fibrillation, and 24 (0.04%) for ventricular tachycardia attributed to the use of remdesivir. Reported events of bradyarrhythmia were further divided and analyzed into men vs women, and different age groups of years 18-64, 65-85, >85. Total events of bradyarrhythmia among men (238, 6.5%) vs women (141, 6.4%) were not significantly different. Among all the age groups, more events were reported in younger women in the age group of 18-64 (12.3%) vs 65-85 (7.9%) vs >85 (6.9%). Conclusion: Multiple studies have shown COVID-19 associated tachyarrhythmias, likely secondary to the myocardial damage due to hypoxia. Few studies have also suggested bradyarrhythmias in these patients. Our analysis of the FAERS database also showed many reported AEs of bradyarrhythmia attributed to the use of remdesivir. Postulated mechanisms include;medication side effects, damage to the SA node as a complication of the COVID-19 disease process, and electrolyte imbalance due to the renal failure. Close surveillance of these patients with early diagnosis can lead to prompt discontinuation of the medication, which can further decrease the mortality related to bradyarrhythmias. Further studies are required to identify the at-risk population and to better understand the risk of bradyarrhythmia associated with remdesivir.

Association of Respiratory Tract Infections causing Alterations in Lung Parenchyma and Pulmonary Vasculature with Body Electrolyte Imbalance

Aim: The assessment of serum electrolytes at the time of initial presentation of the patient with respiratory tract infection possibly causing lung parenchyma and pulmonary vasculature damage and serial monitoring during the stay could be beneficial in order to determine when and how to take remedial action when necessary. Methodology: A non-probability sampling was done on 139 subjects with suspected respiratory tract infection. For confirmation, culture, MTB PCR, COVID-19 testing was done to diagnose the nature of infection. Serum electrolytes were tested on chemical analyses Alinity instrument. Results: Most common infections found were COVID-19 and bacterial (n=59) collectively in a co-morbid state. Mycobacterium tuberculosis and fungal infections were also found in (n=8) each. Electrolytes imbalance was markedly observed in high prevalence amongst Tuberculosis and COVID-19 patients but also showed significant association with other respiratory investigated infections. Conclusion: A robust association of electrolyte imbalance was found in all cases presented with upper or lower respiratory tract infections.

ATYPICAL HAEMOLYTIC UREMIC SYNDROME ASSOCIATED WITH COVID-19: CASE REPORT

BACKGROUND AND AIMS: Renal manifestations are common in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report here the case of a patient with confirmed SARS-CoV-2 infection with the clinical picture of atypical haemolytic uremic syndrome (aHUS). METHOD: Case report RESULTS: Our case is a 31-year-old man with a nasopharyngeal swab with real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 positive, who was hospitalized in the Clinic of Infectious Diseases. His medical history had a respiratory illness of 7-day evolution characterized by cough, fever, dyspnoea, muscle pain, nausea, vomiting and non-bloody diarrhoea, and decreased urine output with dark colour urine. The chest computed tomography (CT) scan showed few rounded ground-glass opacities. Laboratory tests at admission revealed the following: (i) acute kidney injury stage 3 with a serum creatinine of 3.85 mg/dL (basal value 0.9 mg/dL);serum urea 221 mg/dL. His urinary volume in the first 24 h of hospitalization was 800 mL. (ii) Severe haemolytic anaemia with haemoglobin (Hgb) level of 3.7 g/dL, and peripheral smear showing large number of schistocytes, haptoglobin <10 mg/dL and indirect bilirubin 9.7 mg/dL, direct coombs testing was negative;reticulocyte count 8.9%. (iii) Severe thrombocytopaenia with platelet count of 25 000/μL, prothrombin time 45%, international normalized ratio 1.7, D-dimer 1082 ng/dL and fibrinogen 880 mg/dL. Increased blood levels of enzymes and inflammatory markers were present: lactate dehydrogenase 1867 U/L and protein C reactive 9.1 mg/dL. Electrolyte disturbances characterized by hyperkalaemia, hyperphosphatemia, hypocalcaemia and severe metabolic acidosis. Dynamic changes of laboratory data are presented in Table 1. The usual liver panel tests, alkaline phosphatase, γ -glutamyl transferase and albuminemia were normal. Toxic hepatitis was excluded. Hepatobiliary and spleen imaging (ultrasonography) was normal. ELISA serologic tests for HIV, hepatitis B, hepatitis C virus and cytomegalovirus were negative. Serological and virological tests for hepatitis A, B, C, HIV and CMV were negative. Stool was negative for Shiga toxin-producing Escherichia coli (STEC). The results of antinuclear antibodies and anti-smooth-muscle antibodies were negative, C3 serum level was mildly depressed (82 mg/dL;normal range 88- 201 mg/dL) and C4 serum level was normal (20 mg/dL;normal range 10-44 mg/dL). ADAMTS13 activity was 90% on day 10. He was treated with broad spectrum antibiotics, intravenous dexamethasone and supportive therapy. One week from admission, renal function recovered, and 1 week after intravascular haemolysis and thrombocytopaenia recovered. The patient was hospitalized for 21 days. CONCLUSION: Close monitoring and early intervention can help for a better outcome of SARS-CoV-2 patients complicated with aHUS.

Magnesium and COVID- 19 - cardiovascular implications

The novel coronavirus SARSCoV- 2 is causing an ongoing worldwide pandemic of COVID-19. The infection with this single-stranded RNA virus appears to be completely asymptomatic in a large fraction of people and many other patients may experience mild symptoms such as fever, cough, anosmia, and myalgia. Some patients need hospitalization and some will develop an acute respiratory distress syndrome (ARDS), and a significant subset will require treatment in the intensive care unit to provide respiratory ventilator support. Unfortunately, there is no causal curative treatment, so far. In this context, the potential prophylactic and therapeutic options for the novel SARS-CoV-2 infection and corresponding COVID-19, as well as interventions with special nutrients like zinc or vitamin D are discussed, especially due to their role in the immune system [1]. Possible drugs for the treatment of COVID-19 increase the risk of QT interval prolongation, e.g., chloroquine, hydroxychloroquine, azithromycin, lopinavir, ritonavir. QT prolongation can provoke life-threatening torsade-de-pointes arrhythmias (TdP) and sudden cardiac death. Mg deficiency and other electrolyte imbalances also belong to the known risk factors for QT prolongation and TdP. Consequently, it is recommended to obtain baseline assessment of Mg and other electrolytes and to correct deficiencies before using QT-prolonging drugs. Keeping serum potassium levels and Mg levels above 4 mmol/L and 3 mg/ dL (= 1.23 mmol/L), respectively, in COVID-19 patients treated with QT-prolonging drugs proved to be effective in preventing QT prolongation, and no arrhythmias or sudden cardiac arrest were registered. This is above the upper limit of the reference range (usually ∼ 1.1 mmol/L). In a single-center study (n = 524), a specially designed monitoring process in COVID-19 patients (with COVID-19-related medication) identified a high proportion of patients with QT prolongation (n = 103, corresponding to 19.7%). As part of the medical support, reaching Mg and potassium in the reference range was recommended [2, 3]. Administration of intravenous Mg sulfate is the therapy of choice for hemodynamically stable TdP, regardless of whether the patient is hypomagnesemic or has a normal serum Mg concentration. This may be a relevant reason why the German Federal Institute of Drugs and Medical Devices (BfArM) put Mg (parenteral) on a list with drugs whose need is greatly increased with treatment of COVID-19 patients in intensive care units [4]. On the other hand, hypomagnesemia generally is a common occurrence in intensive care patients (regardless of COVID-19) with a prevalence up to 65%, associated with an increased mortality rate, higher need for ventilator support, increased incidence of sepsis, and longer hospital stays [5]. There is increasing evidence that viral infection of the endothelial cells plays a key role in multiorgan participation and severe courses of COVID-19. This finding provides a rationale for therapies to stabilize the endothelium, in particular for vulnerable patients with pre-existing endothelial dysfunction which can be found for example in cardiovascular disease, diabetes, hypertension, obesity, all of which are associated with adverse outcomes in COVID-19. Interestingly, Mg is known to be crucial for endothelial function and its deficiency causes endothelial dysfunction with impaired endothelial-dependent vasodilation. In a meta-analysis of randomized, controlled trials (RCTs), oral Mg supplementation was shown to improve flow-mediated dilation as a marker of endothelial function. It is therefore plausible to assume that Mg deficiency further worsens the consequences of an infection with SARS-CoV-2 via induction of endothelial dysfunction. In this context, the frequent occurrence of thrombotic embolism in COVID-19 is worth mentioning. Animal and human data suggest that Mg functions as an antithrombotic agent. Hence, increased platelet reactivity and thrombosis are possible cardiovascular manifestations of Mg deficiency [6, 7]. Furthermore, increased inflammation in Mg deficiency has to be kept in mind. Experimental studies show an increased incidence of markers for inflammation in case of Mg deficiency, e.g., leukocyte and macrophage activation, pro-inflammatory molecules such as interleukin-1, interleukin-6, tumor necrosis factor, vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, and excessive production of free radicals. Generally, Mg deficiency is considered as a significant contributor to chronic lowgrade inflammation and, therefore, risk factor for a variety of pathological conditions such as cardiovascular disease, hypertension, and diabetes. In meta-analyses of RCTs, Mg supplementation was shown to reduce C-reactive protein levels. Whether Mg deficiency or Mg supplementation may impact the inflammatory event in COVID-19 has to be investigated in clinical studies [7, 8]. To our knowledge, there are no systematic studies so far examining Mg status in COVID-19 patients. In a pooled analysis, Lippi et al. [6] confirmed that COVID-19 severity was associated with lower serum concentrations of sodium, potassium, and calcium. Therefore, measuring electrolytes at initial presentation and monitoring during hospitalization is recommended in order to be able to take appropriate corrective measures in good time. Unfortunately, serum Mg was not determined in the studies analyzed. In the above-mentioned study of Jain et al. [3], 30.1% of the COVID-19 patients with QT prolongation showed hypomagnesemia. Conclusion: In view of the relationships described, it is plausible to assume that Mg deficiency may decrease the resistance against infection with SARS-CoV-2 and, most notably, may worsen the course of COVID-19. Hence, Mg deficiency could be a risk factor for severe COVID-19, comparable to cardiovascular disease, diabetes, chronic respiratory disease, older age, obesity, amongst others. Interestingly, Mg deficiency is often associated with these risk factors or seen as comorbidity. However, more research questions need to be addressed before definitive conclusions can be drawn [8, 9].