Liver biomarkers for prognosis in COVID-19

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).Mortality attributable to COVID-19 remains considerably high, with case fatality rates as high as 8-11%. Early medical intervention in patients who are seriously and critically ill with COVID-19 reduces fatal outcomes. Thus, there is an urgent need to identify biomarkers that could help clinicians determine which patients with SARS-CoV-2 infection are at a higher risk of developing the most adverse outcomes, which include intensive care unit (ICU) admission, invasive ventilation, and death. In COVID-19 patients experiencing the most severe form of the disease, tests of liver function are frequently abnormal and liver enzymes are found to be elevated. For this reason, we examine the most promising liver biomarkers for COVID-19 prognosis in an effort to help clinicians predict the risk of ARDS, ICU admission, and death at hospital admission. In patients meeting hospitalization criteria for COVID-19, serum albumin < 36 g/L is an independent risk factor for ICU admission, with an AUC of 0.989, whereas lactate dehydrogenase (LDH) values > 365 U/L accurately predict death with an AUC of 0.943.The clinical scores COVID-GRAM and SOFA that include measures of liver function such as albumin, LDH, and total bilirubin are also good predictors of pneumonia development, ICU admission, and death, with AUC values ranging from 0.88 to 0.978.Thus, serum albumin and LDH, together with clinical risk scores such as COVID-GRAM and SOFA, are the most accurate biomarkers in the prognosis of COVID-19.Copyright © 2021 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

Monoclonal antibodies to the interleukin-6 receptor in the treatment of COVID-19 in patients with chronic kidney disease

Interleukin-6 (IL-6) plays a key role in the pathogenesis of COVID-19, which determines the indications for the therapeutic use of its antagonists. However, data on their effectiveness and optimal timing of appointment are contradictory. The question of the possibility of their use in patients with impaired kidney function has not been studied. The aim of the study is to evaluate the efficacy and safety of the use of monoclonal antibodies to IL-6 receptors in COVID-19 in patients with chronic kidney disease (CKD) of stages 2-5 (predialysis) who do not need renal replacement therapy. Material and methods. A clinical retrospective uncontrolled single-center study included 45 patients (60% of men) with CKD stages 2-5 aged 22-95 years (median - 58 years) hospitalized with predominantly severe uncritical COVID-19 infection. Treatment of COVID-19 was carried out in accordance with the Interim guidelines for the prevention and treatment of new coronavirus infection of the Ministry of Health of Russian Federation. Results. The majority of patients (n=36;73.3%) had CKD stage 3b-5, CKD stage 2 was in 7 (15.5%) and stage 3a - in 5 (11.1%) patients. The median serum creatinine level (Cr) was 164 [131;292] mumol/l, glomerular filtration rate (GFR) was 30 [13;49] ml/min/1.73 m2, CRP 67.5 [37.2;106.75] mg/l. The introduction of monoclonal antibody to IL-6 receptors led to a decrease in the activity of the infectious process (CRP 1.55 [0.33;4.15] mg/l, p<0.001), regression of pneumonia, which did not require mechanical ventilation and hospitalization in the intensive care unit. According to the decision of the medical commission, patients were injected with monoclonal antibodies to IL-6 receptors: tocilizumab (n=36;80%), levilimab (n=2;4.4%), combined therapy with two drugs (n=7;15.5%). Therapy with IL-6 antagonists did not have a negative effect on kidney function. The levels of Cr decreased on average from 224.3+/-145.2 mmol/l at admission to 160+/-92.55 mmol/l at discharge (p<0.001), GFR increased from 32.6+/-20.9 ml/min/1.73 m2 at admission to 53+/-31.7 ml/min/1.73 m2 at discharge (p<0.001). In the majority of patients (n=36, 80%) GFR has risen, and only in 9 (20%) cases it remained approximately at the same low level. No serious adverse events have been reported with the use of IL-6 antagonists, as well as concomitant infectious complications. No deaths have been reported. The median length of stay in bed was 14 [10;19] days. Conclusion. The results of the study allow us to state that in patients with CKD, monoclonal antibodies to IL-6 receptors have a good safety profile and can be successfully used in moderate and severe forms of COVID-19, regardless of the state of kidney function.Copyright © 2022 by the authors.

Personalized approach to the management of a patient with COVID-19 with a complicated comorbid background

The aim of the work is to form the principles of a personalized approach to the management of patients with COVID-19 with a complicated comorbid background. Material and methods. The article describes a clinical case of successful recovery of an 87-year-old patient from a new coronavirus infection COVID-19, complicated by pneumonia involving 36% of the lung parenchyma area. Along with age, the situation was aggravated by the comorbid status of the patient: the presence of chronic lymphocytic leukemia, hypertension, mechanical prostheses of the mitral and aortic valves, postinfarction cardiosclerosis, paroxysmal atrial fibrillation, type 2 diabetes mellitus, stage 4 CKD, anemic syndrome, and subclinical hypothyroidism. Results. The C-reactive protein level at admission was 114.46 mg/L. The patient refused hospitalization. Baricitinib 4 mg, favipiravir according to the scheme, vitamin D 2000 units were prescribed for the previously taken therapy. Already after 3 days, C-reactive protein decreased by 4.6 times, and by the 8th day by 15.5 times and amounted to 7.38 mg/ml. The temperature returned to normal on day 2 from the start of baricitinib. In dynamics, a decrease in creatinine level to 177.0 mumol/l was noted, the glomerular filtration rate increased to 30 ml/min/1.73 m2, which corresponded to stage 3b of CKD (a pronounced decrease in glomerular filtration rate). Conclusion. Despite the age of the patient, many comorbidities, each of which could be fatal, the timely use of baricitinib on an outpatient basis made it possible to stop the progressive course of the disease.Copyright © Eco-Vector, 2023. All rights reserved.

Impact of Kidney Damage on the Course and Prognosis of COVID-19 Infection According to the International Registry <<Analysis of Chronic Non-Infectious Diseases Dynamics After Covid-19 Infection in Adult Patients>>

Objective. To study the course of the new coronavirus infection in patients with chronic kidney disease (CKD), to identify cases of acute kidney injury (AKI) in the setting of COVID-19 infection, and to access the impact of renal function on prognosis in these categories of patients during the acute phase and after hospitalization, at 3, 6, and 12 months after recovery. Materials and methods. The ACTIV and ACTIV 2 registries included men and women older than 18 years with a diagnosis of COVID-19 based on a positive PCR test for COVID-19 and a characteristic chest X-ray or computed tomography chest scan. Results. A total of 9364 patients (4404 men, average age59 [48-69]) were included in the analysis. 716 (7.67 %) patients had CKD. 8496 (90,7 %) patients had their glomerular filtration rate (GFR) measured during hospitalization, and the values were distributed as follows: >=90 ml/min/1.73m2 - in 4289 (50,5 %) patients, 89-60 ml/min/1.73m2 - in 3150 (37,1 %) patients, 59-45 ml/min/1.73m2 - in 613 (7,22 %), 44-30 ml/min/1.73m2 - in 253 (2,98 %), 29-15 ml/min/1.73m2 - in 110 (1,29 %), <15 ml/min/1.73m2 - in 81 (0,95 %) patients. 11.6 % of the subjects (n=1068) developed AKI during hospitalization. This complication was reported more often than cytokine storm (in 7.46 % in 687 patients, p<0,001) or sepsis (in 0.17 % in 16 patients, p=620). CKD increased the risk of death by 3.94-fold in patients with COVID-19 during hospitalization compared with patients without CKD. The mortality of patients with AKI during hospitalization was 3.94 times higher than the mortality of those without AKI. CKD also affected long-term survival after hospitalization: within 3 months of follow-up, the risk of death in patients with CKD increased 4.88-fold, within 6 months - 4.24-fold, after 12 months - 8.36-fold. Conclusion. The prevalence of CKD in COVID-19 patients is similar to that in the general population. AKI developed in 11.6 % of cases with COVID-19 infection and was observed more frequently in patients with overweight and hyperglycemia. CKD and AKI increased the risk of hospital mortality in patients with COVID-19. In the group of patients with CKD, mortality increased in the post-COVID period, 3, 6 and 12 months after. The high mortality rate of patients who had AKI during the coronavirus infection was observed only in the first 3 months of follow-up in the post-COVID period.Copyright © 2023 The authors.

Incident New Onset Diabetes after Covid-19 Infection: A National Multicenter Cohort

Background: It is known that survivors of acute SARS-CoV-2 infection can experience a complex disease known as post-acute sequelae of COVID-19 (PASC). The clinical manifestations of acute COVID-19 have been well characterized however less is known about the risk of new onset diabetes mellitus (DM) in the post-acute phase of COVID-19. Method(s): An adult cohort with confirmed COVID-19 (by diagnosis or positive test) and without COVID-19 was sampled from a large national health research network between January 1st, 2020 and July 8th, 2022. We investigated the outcomes of a new diagnosis of DM (type I or II) occurring after COVID-19 through 12 months after infection. Risk estimates [incidence, relative risk (RR), attributable risk] were used to describe the probability of incident post-COVID diabetes. Hazard ratios and 95% confidence intervals were used to describe risk factors associated with new diabetes. Result(s): The 3-month probability of new diabetes was 2.48/1,000 among COVID+ and the relative risk (RR) of new diabetes was highest at 12 months [8.94 (8.54, 9.36)]. Vitamin D deficiency [HR: 1.52 (95% CI: 1.42, 1.63)] was associated with increased risk of T2DM and having vitamin D deficiency with either obesity (BMI > 30 kg/m2) or kidney dysfunction (GFR < 60) was associated with more than five times increased risk of T1DM. Conclusion(s): We observed a large proportion of excess diabetes starting at 3 months post COVID infection. Traditional risk factors for diabetes, omicron variant, and vitamin D deficiency are associated with increased risk of new diabetes outcome. PASC care should involve identification and management of diabetes. (Figure Presented).

A CLINICAL CASE OF SARS-CoV-2 INFECTION COMPLICATED BY NEPHROGENIC PULMONARY EDEMA AND COVID-ASSOCIATED PNEUMONITIS, ALVEOLITIS.

COVID-19 is a highly transmissible disease with severe course especially in patients with nephrogenic hypertensive disease and chronic kidney disease due to a higher incidence of all-type infections than in the general population. The aim of the study is to describe a clinical case of SARS-CoV-2 infection complicated by nephrogenic pulmonary edema and COVID-associated pneumonitis, alveolitis. Description of the case. Patient K.S., born in 1975, was hospitalized 24 hours after symptom onset at emergency hospital due to complaints of increased blood pressure up to 180-200/110-120 mm Hg, temperature up to 38.7degreeC, dry cough, feeling of heaviness in the chest, change in urine color. PCR smear for SARS-CoV-2 was positive. Computed tomography revealed a pattern of bilateral COVID-associated pneumonitis, alveolitis, with 75% involvement. The electrocardiogram revealed signs of left ventricular myocardial hypertrophy. Ultrasound examination showed numerous cysts in the kidneys. Urinalysis at admission: leukocytes - 499, erythrocytes - 386. Glomerular filtration rate (CKD-EPI: 29 ml/min/1.73 m2) and corresponds to stage IV of chronic kidney disease. Coagulogram: fibrinogen: 32.3 (1.6-4.0) g/l, D-dimer: 663 (0-250). Despite the treatment, the patient's condition worsened, the phenomena of cardiopulmonary and renal insufficiency increased, which led to a fatal outcome. During a virological study of sectional material: SARS-CoV-2 coronavirus RNA was found in the lung and kidneys. Signs of bilateral COVID-associated pneumonitis, alveolitis with diffuse cellular infiltrates in combination with changes in the alveolar apparatus, signs of pulmonary edema were revealed. Heart-related signs - swelling of the interstitium, fragmented muscle fibers, some of them hypertrophied, a wave-like deformation of cardiomyocytes, blurring of the transverse striation. Arteries with thickened sclerosed walls. In the kidneys - diffuse damage to the proximal tubules of the nephron with areas of cortical and proximal necronephrosis, areas of fibrinoid swelling. Conclusion. The cause of death of a 45-year-old patient was a severe course of bilateral COVID-associated pneumonitis, alveolitis, which contributed to the development of renal medullary hypoxia and type 1 cardiorenal syndrome, which led to early nephrogenic pulmonary edema.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.

The Complexities of Managing Hypertriglyceridemia-Induced Pancreatitis in a Critically-Ill COVID-19 Patient

Introduction: Hypertriglyceridemia-induced pancreatitis (HTP) is a variant of pancreatitis requiring unique management. The complications of COVID-19 and its treatments can make HTP therapy more nuanced. This case describes a patient who presented in diabetic ketoacidosis (DKA) with HTP, and COVID-19. The patient developed renal and respiratory failure, necessitating hemodialysis (HD) and extracorporeal membrane oxygenation (ECMO), complicating an otherwise straightforward medical management plan. Case Description: A morbidly obese (BMI 38.9 kg/m2) 43-year-old male presented to an outside hospital with abdominal pain, and vomiting, and was found to have HTP with triglycerides (TG) >2000 mg/dL (<149 mg/dL) and presumed new-onset type 2 Diabetes (HbA1c 10.9%) with DKA. Treatment with fluids, intravenous (IV) insulin infusion and plasmapheresis were initiated. He developed hypoxia after receiving over 17 liters of fluids and was intubated, subsequently developing renal failure and was transferred to our tertiary center for HD and ECMO. On admission, he tested positive for COVID-19, rhabdomyolysis [creatinine kinase 5600 U/L (30-200 U/L)], HTP [TG 783 mg/dL (<149 mg/dL), lipase 461 U/l (7-60 U/L)], glucose 269 mg/dL (not in DKA), transaminitis [AST 184 U/L (4-40 U/L), ALT 61 U/L (4-41 U/L)] and renal failure (GFR 10 ml/min/1.73m2). IV insulin infusion was initiated for hyperglycemia worsened by COVID-19 dexamethasone treatment. Plasmapheresis was performed twice with minimal effect at maintaining a low TG. Fenofibrate was not initiated due to renal failure;Lovaza could not be given via oral gastric tube;Atorvastatin was attempted once rhabdomyolysis resolved, with subsequent worsening of liver function tests. Heparin infusion was initiated for deep vein thrombosis treatment and HTP but was stopped after development of heparin induced thrombocytopenia. The patient developed worsening hypoglycemia requiring cessation of IV insulin, hypotension requiring maximum pressor support, and worsening sepsis leading to his death. Discussion(s): This case illustrates the challenges of managing a patient with HTP and COVID-19. It demonstrates how a normally straightforward treatment algorithm can become increasingly complex when factoring the patient's comorbid conditions. The case highlights the importance of knowing both treatment indications and contraindications for HTP. In this case, HTP may have been the initial diagnosis, straightforward for most endocrinologists, but its treatments and comorbid conditions ultimately made the landscape more challenging, limiting effective management and ultimately leading to this patient's demise.Copyright © 2023

Personalized approach to the management of a patient with COVID-19 with a complicated comorbid background.

The aim of the work is to form the principles of a personalized approach to the management of patients with COVID-19 with a complicated comorbid background. Material and methods. The article describes a clinical case of successful recovery of an 87-year-old patient from a new coronavirus infection COVID-19, complicated by pneumonia involving 36% of the lung parenchyma area. Along with age, the situation was aggravated by the comorbid status of the patient: the presence of chronic lymphocytic leukemia, hypertension, mechanical prostheses of the mitral and aortic valves, postinfarction cardiosclerosis, paroxysmal atrial fibrillation, type 2 diabetes mellitus, stage 4 CKD, anemic syndrome, and subclinical hypothyroidism. Results. The C-reactive protein level at admission was 114.46 mg/L. The patient refused hospitalization. Baricitinib 4 mg, favipiravir according to the scheme, vitamin D 2000 units were prescribed for the previously taken therapy. Already after 3 days, C-reactive protein decreased by 4.6 times, and by the 8th day by 15.5 times and amounted to 7.38 mg/ml. The temperature returned to normal on day 2 from the start of baricitinib. In dynamics, a decrease in creatinine level to 177.0 mumol/l was noted, the glomerular filtration rate increased to 30 ml/min/1.73 m2, which corresponded to stage 3b of CKD (a pronounced decrease in glomerular filtration rate). Conclusion. Despite the age of the patient, many comorbidities, each of which could be fatal, the timely use of baricitinib on an outpatient basis made it possible to stop the progressive course of the disease.Copyright © Eco-Vector, 2023. All rights reserved.

High prevalence of asymptomatic SARS-CoV-2 infection in a cohort of liver transplant recipients in central Italy

Asymptomatic subjects account for 25 to 45% of SARS-CoV-2 infections, and in particular, subjects on mild immunosuppressive therapy may have symptoms masked and could spread virus for an extended period of time. To determine the cumulative incidence of symptomatic and asymptomatic SARS-CoV-2 infections and associated risk factors, we conducted a prospective clinical and serological survey in a cohort of 278 liver transplant recipients (LTRs) from Central Italy. Three different serology tests were performed every 4 months in 259 LTRs between April 2020 and April 2021: one based on raw extract of whole SARS-CoV-2 virus and two on specific viral antigens (nucleoprotein and receptor binding domain) to detect specific IgG, IgM and IgA. Hundred fifteen LTRs who reported symptoms or close contact with a SARS-CoV-2-positive subject, or had a positive serological result underwent molecular testing by standard screening procedures (RT-PCR on naso-pharyngeal swab). Thirty-one past or active SARS-CoV-2 infections were identified: 14 had positive molecular test (64% symptomatic), and 17 had positive serology only (18% symptomatic). SARS-CoV-2 infection was not statistically related to gender, age, obesity, diabetes, renal impairment, type of anti-rejection therapy or time from transplant. Asymptomatic SARS-CoV-2 cases (61.3%) were more frequent in males and in those with glomerular filtrate rate >50 ml/min. Overall, the addition of repeated serology to standard diagnostic molecular protocols increased detection of SARS-CoV-2 infection from 5.1% to 10.9%. Anti-SARS-CoV-2 seroprevalence among our LTRs (11.2%) is comparable to the general population of Central Italy, considered a medium-impact area. Only one asymptomatic subject (6%) was found to carry SARS-CoV-2 in respiratory tract at the time of serological diagnosis.Copyright © 2021 The Authors

Evaluation of Nirmatrelvir/Ritonavir Use and Effectiveness

Background and Importance Nirmatrelvir/ritonavir (PAXLOVID) is a recently approved drug to prevent progression in high-risk COVID-19-infected patients. Aim and Objectives To evaluate prescribing and dispensing of PAXLOVID and the proportion of patients with hospitalisation or death from any cause at 28 day. Material and Methods Descriptive, retrospective, observational study carried out between May and August 2022 in a secondlevel hospital. All patients with PAXLOVID prescription were selected. Sources of information were: electronic medical records and the prescription programme. The Variables analysed were: sex, age, risk factors, indications, interactions, dispensation (yes/no) and final treatment received. Risk factors were evaluated with our country's drug regulatory agency (DRA) recommendations to assesed the indication. Efficacy was assessed by the proportion of patients admitted to hospital and 28-day mortality. Results PAXLOVID was prescribed to 34 patients, 14 (41.2%) were women. The median age was 76.3 years old [RIQ 25.4]. Main indications for PAXLOVID were: to be undergoing treatment with myelotoxic chemotherapy (32.3%), corticosteroids or other immunosuppressants (29.4%);being over 80 years of age and presenting specific Risk factors (14.7%) and primary immunodeficiency (5.8%). 21 patients (61.8%) had some relevant interaction with their usual medication. The most frequent interactions were with statins (23.5%), analgesics (20.6%), oral anticoagulants (12%), antiarrhythmics (8.8%), antiplatelet drugs (5.8%), antidepressants (5.8%) and antidiarrhoeals (5.8%). After Validation by the Pharmacy Service, 11 patients (32.4%) did not receive PAXLOVID, 5 because they did not meet DRA criteria, 2 because their glomerular filtration rate was less than 30 ml/min and 4 because they had incompatible interactions. 4 patients finally received 3 days-remdesivir. Among patients who received PAXLOVID, 82.26% received full doses, with 4 patients (11.76%) requiring adjustment for renal impairment. 3 patients (13%) were hospitalised in the first month, none died. Conclusion and Relevance The main indications for which PAXLOVID was prescribed were patients undergoing chemotherapy and/or immunosuppressive treatments. Interactions with PAXLOVID were frequent and in some cases limited treatment. Validation by Pharmacy Service prevented a considerable number of patients from receiving PAXLOVID when it was no-indicated or when they had insurmountable interactions, also allowed patients to receive the dose adjusted for renal impairment. PAXLOVID was effective in avoiding hospital admission and mortality in the majority of patients.

New Onset Renal Replacement Therapy Is a Predictor of Covid-19 Adverse Outcome in Patients with Advanced Chronic Kidney Disease Due to Type 2 Diabetes Mellitus

Introduction: The patients with diabetic kidney disease (DKD) due to type 2 diabetes mellitus (T2DM) are at a high risk of adverse outcomes of COVID-19. In some cases, rapidly progressive kidney injury requires urgent initiation of renal replacement therapy (RRT) - hemodialysis de novo (HD de novo). The objective of this study is to identify risks factors of adverse outcomes and predictive value of HD de novo in patients with DKD due to T2DM and COVID-19. Method(s): The patients with chronic kidney disease 4-5 stages (CKD 4-5) with laboratory-confirmed COVID-19 were included in the retrospective observational study. The observation period 04.01-10.30.2020. Data were collected from electronic medical database. The following independent variables were analyzed at hospital admission: age, gender, body mass index (BMI), general comorbidity (Charlson Index, CCI), the insulin demand (InsD), fasting blood glucose (FBG), glomerular filtration rate (GFR), Plasma creatinine (Pcr), serum albumin (SA), proteinuria, time from onset to admission, NEWS2-scale points, pulmonary involvement (Chest CT), Hb, WBC, lymphocytes, platelet count, LDH, CPR, ferritin, D-dimer, procalcitonin, Interleukin-6. The observation group was divided into subgroups: 1 - HD not required (HD n/r), 2 - HD de novo. Result(s): A total of 55 patients were included. Mediana age was 69 y (IQR 64;80), fe-males 59%. The overall mortality - 38.2%. In 18 patients (32.7%) HD de novo was initiated due to rapidly progressive renal failure. The results of comparative analyses of demographic, initial clinical and laboratory data are presented in Tables (*Mann-Whitney U-test;IQR, interquartile range;Me, mediana). [Formula presented] [Formula presented] The mortality in both subgroups was 21.6 % vs 72.2 % respectively (p <0,001). HD de novo was determined as an independent predictor of adverse outcome (OR 9.42;95% CI, 2.58-34.4, p = 0.001). The analysis showed that FBG >= 10 mmol/L at admission (OR, 3.38;95% CI, 1.04-10.98, p = 0.050), SA at admission <= 35 g/L (OR 3.41;95% CI, 1.00-11.55, p = 0.050), News2 >4 points (OR 5.60;95% CI, 1.67-19.47, p = 0.006), GFR <= 20 ml/min/1,73m2 at admission (OR 4.24;95%;CI 1.29-13.99, p = 0.020) were independent predictors of HD de novo. Cumulative survival in subgroup HD de novo was 10% (significantly less, than in patients HD n/r) (Fig.). [Formula presented] Conclusion(s): Approximately every third patient with advanced nondialysis DKD required new onset RRT.New onset RRT is an independent predictor of lethal outcome of COVID-19. High FBG, low SA, low GFR and high NEWS2 score at admission are the risk factors of HD initiation during hospitalization. No conflict of interestCopyright © 2023

A contrasting diagnosis: iododerma

An 86-year-old woman presented to the emergency department with acute shortness of breath. She was treated with intravenous furosemide for acute-on-chronic heart failure. Her past medical history included atrial fibrillation, hypertension, diverticulosis and hypothyroidism. Rivaroxaban and levothyroxine were her only long-term medications. On day 5 of hospital admission, she developed painful haemorrhagic and purulent bullae on her dorsal hands, head and neck. These evolved to large suppurative, vegetative plaques over a 72 h period and she developed additional lesions on her trunk, upper back and thighs. The patient had routine blood tests, which showed a raised C-reactive protein at 260 mg L-1, and an acute kidney injury with a glomerular filtration rate of 54 mL-1 min-1. She had a negative COVID-19 swab, and swabs from the lesions for bacterial culture and viral polymerase chain reaction were negative. She had a normal serum protein electrophoresis, immunoglobulin, antinuclear antibody and antineutrophil cytoplasmic antibody. She had computed tomography of her chest 24 h prior to the onset of her lesions, which showed mild bilateral pleural effusions in keeping with fluid overload secondary to heart failure. A biopsy taken from her hand showed orthokeratosis and parakeratosis, and there was bulla formation subepidermally. There was a dense neutrophilic infiltrate with microabscess formation with scattered eosinophils and lymphocytes. There was no evidence of vasculitis. Direct immunofluorescence was negative and a tissue culture for atypical mycobacteria was negative. The patient was commenced on high-dose intravenous methylprednisolone at 500 mg for 3 days followed by 40 mg prednisolone orally for 1 week, but there was a limited response. Our initial differential was Sweet syndrome or pyoderma vegetans;however, the patient had no fevers and no risk factors (malignancy, inflammatory disease, infection, etc.). She also had no response to high-dose oral prednisolone. Given the timing of her CT examination in relation to her acute dermatosis and the use of radioiodine for contrast, we assessed the patient's serum iodine and urine iodine. These were both high at 1.02 mmol L-1 (reference interval 0.32- 0.63) and 3.46 mmol L-1 (reference interval 0.0-2.43), respectively. A diagnosis of iododerma was made. The patient's eruption slowly resolved and at 12 weeks there was evidence of postinflammatory skin changes only. Her urine and serum iodine were rechecked, and both had normalized. In the last 20 years there have been approximately 20 case reports of iododerma. Most have been following iodine contrast use in patients with abnormal kidney function, like our patient. Most describe an acneiform eruption that subsequently evolves to vegetative plaques (Chalela JG, Aguilar L. Iododerma from contrast material. N Engl J Med 2016;374: 2477). Iododerma is largely a diagnosis of exclusion, but histopathology and urine and serum iodine levels can help support diagnosis.

Outcomes in Patients with Diabetes Mellitus Affected by COVID-19

Background: An important prognostic factor in any form of infection seems to be glucose control in patients with diabetes mellitus. Therefore, we examined the effects of optimal glycemic control in patients with diabetes mellitus and affected by COVID-19. Interplay between severities of COVID-19 in earliest data on the pandemic. Relative risks of death 1.7 to 2.2 based on studies from China and Italy. People with diabetes appear to be at greater risk of severe disease. 31% mortality in Wuhan vs 14% hospitalized non DM. Most endemic related to T2DM rather than T1DM. Obesity and insulin resistance may be particular risk factors. Similar finding with previous SARS coronavirus outbreaks. (Ref, Wu, Jama 2020 Graselli Jama 2020 Zhon). Further study from France Coranado study including 1317 people with diabetes mellitus and COVID-19 in 53 hospitals, 88% with T2DM, 3% new diagnosis, mean BMI 28 kg/m2, HBA1c 65 mmol/mol. Primary endpoint death or ventilation at day 7. 410 required Intensive care unit admissions, 267 ventilated, 140 deaths and 237 patient discharged by day 7. Comprehensive dataset from UK comparing primary care and national diabetes audited data reported 33% of in hospital death related to COVID-19 occurred in people with diabetes (31.3% T2DM, 1.5% for type 1 diabetes). 5.1% of total individual population had diabetes. Adjusted relative risk of death of death 2.9% for type 1 diabetes, 1.8% for type 2 diabetes. It was also noted there is clear association between renal function and outcome with increased mortality with e GFR<60 ml/min/1.73 m2. Further data from the United States the authors further compared the outcome for those with hyperglycemia with those with normoglycemia at admission. 41% had poor outcome in those with hyperglycemia without known diabetes vs under 15% in context of COVID-19 for those with previous diabetes. Marked hyperglycemia at admission had strong impact on prognosis and the development of diabetes mellitus in context of COVID-19 is particular serious events. (Bode et al, J Diab Sci Tech, 2020). These worked was also identified a significant increase in total death in diabetes during 2020. Objective(s): To evaluate the effect of optimal glycemic control on the outcome for patients with type 2 diabetes affected by COVID- 19 infection. Method(s): This is a retrospective analysis of 100 patients with type 2 diabetes, who were affected by moderate disease of COVID-19 infection and admitted to Fujairah hospital (UAE), compared with 100 non diabetic patient admitted to the same hospital, with the same severity of COVID-19 disease. Result(s): Out of 200 patients studied, 100 patients were non-diabetic and 100 patients were having diabetes mellitus. In the diabetic group, all patients were diagnosed to have diabetes already before admission, and these 100 (100%) were treated with insulin infusion or basal -bolus regime. At baseline, D-dimer levels were not significantly higher in the diabetic group (mean D-dimer = 1.327) than in the normoglycemic group (mean of D-dimer = 1.544) (P < 0.001). Even though all patients were on standard treatment for COVID-19 infection, IL-6 and D-dimer levels persisted higher in patients with diabetes mellitus during hospitalization. Patients with diabetes had a higher risk of severe disease and prolonged length of stay and death 7% deceased (n=7), than those without diabetes and with normoglycemia.5% (n=5) deceased with length of stay of 13.7 days for diabetic group and 12.6 days for non-diabetic group. It was shown in our study, that there are contributory factors like hypertension which was found in 42% of our diabetic patients, and obesity that affect 34% of the same group, ischemic heart disease in three patients, could potentially contributed to the poor outcome and death. We looked to the effect of ethnicity in our patients outcome, the Emirati nationals contributed 14.29% (26) of the cohort, while 13.19% (n=24) were other Arab nationalities and 72.53% (n=132) were South-Asian (chart 5), it clearly showed those people of South-Asian background with high ctopic lipid and increased insulin resistance had worse outcome. Conclusion(s): Insulin infusion and basal/bolus regime was an effective method for achieving glycemic targets and improving outcomes in patients with COVID-19 and it was showed effect in reducing the rate of admission to an ICU, the use of mechanical ventilation and prevent death. Immediate evidence from our study, that COVID-19 was associated with particular challenges in diabetes management. High rate of ketosis and acidosis in people with type 2 diabetes (not normally, ketosis prone), extreme level of hyperglycemia and associated hyperosmolar. Associated with significant acute kidney injury in some cases. Extreme insulin resistance with very high insulin requirement. Many cases of new onset diabetes mellitus mostly required insulin. Some unusual biochemical features, marked fall in serum albumin, variable CRP, Ferritin response, raised D-dimer and high rate of thromboembolic complications. It was shown in our study, that there are contributory factors like hypertension, obesity, ischemic heart disease and presence of acute kidney injury, were potentially contributed to the poor outcome and death.

Status of Antibody against Severe Acute Respiratory Syndrome Coronavirus 2: Preliminary Reports on Seroprevalence of Covid 19 in among Health Care Workers

Introduction: Large number of health care workers (HCW) were infected and died due to COVID-19 infection. It is needed to know the actual seroprevalence of COVID in HCWs to assess the risk and to take protective measures. This study was aimed to measure IgG antibodies against nucleocapsid protein (N) of COVID as a serological marker for detection of viral status in risk prone HCW of Bangladesh and possible association with reno-cardio-metabolic risk factors Methods: This longitudinal study was conducted from May 2021 to January 2022 among physicians and non-physician health care workers (HCW) in three non- COVID designated tertiary hospitals in Bangladesh. Participants' demographic data, medical history and information on past COVID-19 infection and vaccination status were collected. Serial blood samples were collected at 1.5 month in all (n=633) later at 3, 6 and 9 months in vaccinated group. A qualitative measurement of IgG antibody against nucleocapsid protein (N) of SARS-CoV-2 was done by was done by CMIA developed by Abbott (FDA-EUA approved). Result(s): The mean age was 35+/-10years where70% were female. Physician 32%, Nurse 45% and others was 23%. Diabetics were 9.5%, hypertensive 9% and asthma in 5.1%. The two doses of vaccine against COVID-19was completed in 56%. History of past COVID-19 infection was found among 20% participants at recruitment, out of which 13% was diagnosed by rt-PCR. History of past COVID-19 infection was found among 18% participants based on 1gG against N protein. But the subjects in two groups were different. Combination of RTPCR and N protein igG showed 35% seropositive for covid. Comparisons between covid infection positive vs. negative showed only age was different (37+/-11 vs. 34+/-9, years p<0.001) but other risk factors like BMI, SBP, DBP, S Albumin, glucose, hemoglobin were not different (P=NS) between the two groups. Further comparisons for eGFR cut-offs showed higher infection in lower eGFR (infection present vs. absent for >90ml/min group was 17% & 83% and in 60-90 ml/min group 32% &. 68 %). Prevalence of COVID 19 infection based on presence of N antibody (cutoff value >1.5) among vaccinated HCWs at 1.5, 6 and 9 month was 13.6%, 8.8% and 7.7% respectively. The mean titer of IgG (against N protein) >1.5 among vaccinated HCWs at 1.5 month was 3.1+/-1.5 and reduced to 0.87+/-0.96 at month 6 (p<0.001). Conclusion(s): The prevalence of COVID-19 infection in HCWs during the second wave was 35% based on test for RTPR or IgG against N protein positivity. In vaccinated persons, based on antibody against N protein, re-infection rate was around 8% up to 9 months post vaccine. Although no difference was seen for covid infection for cardio-metabolic risk factors, there seems to have some relation of higher infectivity with decreased GFR level. No conflict of interestCopyright © 2023

Last year challenge of Nuclear Medicine: medical radioisotopes supply

Aim/Introduction: 99mTc is used in about 80% of the convencional diagnostic nuclear imaging procedures and represent yearly approximately 30 million examinations/year worldwide a year in diagnostic tests in hospitals, among others by oncology, cardiology and neurology.The production of radiopharmaceuticals for use in Nuclear Medicine has a complex system. It involves carefully calculated production schedules that take into account supply, demand and many logistical operations.The aim of this study is to show how our nuclear medicine department manage the impact of the shortly 99Mo supply chain and consequently, in the 99mTc availability and other radiopharmaceuticals produced in nuclear reactora. Material(s) and Method(s): European nuclear medicine organizations had just pay attention to how the COVID-19 pandemic might affect different parts of the 99Mo supply chain when had to dealt again faced with a new problem;the shortness 99Mo production. There are only five nuclear reactors involved in the production of 99Mo on industrial scale. These aging reactors are subject to unscheduled shutdowns and longer maintenance periods making the 99Mo supply chain vulnerable. In the last few months at our nuclear medicine department we had to reinvent ourselves so as not to completely stop carrying out the previously scheduled exams and therapies. Result(s): The use of technetium generators in Europe represents about 17% - 25% of the worldwide consumption of 99Mo, representing 30,000 exams per day and about 1.1 million doses per month. The main consequences at the IPO-Porto was;Delays in diagnosis/staging, rescheduling exams, change of surgery dates (Sentinel Ganglion and Myocardial Perfusion Cardiacs), weeks of overbooking, delay in follow-up of Glomerular Filtration Rate in pre- or post-transplant patients, postponement of 131I Therapies, Scintigraphy and Whole Body Scintigraphy in patients who were already in hypothyroidism. we had to reinvent the use of 99mTc generators, change exams appointments times, reagroup exams types by defined days and other radiopharmaceutical management tools that were not commonly used. Conclusion(s): Approximately 2/3 of scheduled exams were postponed and we had to deal with weekly and daily stock updates. Our department suggest some measures and procedures that could help with future 99Mo shortages, in order to be ready in future situations and to avoid shortness of production: the creation of a centralized European radiopharmacy system, European policies to encourage long-term investment, homogenization of marketing specifications in the Member States, solid databases of radiopharmaceuticals used/ available in Europe and encouraging cooperation between other countries outside the European Union.

Last year challenge of Nuclear Medicine: medical radioisotopes supply

Aim/Introduction: 99mTc is used in about 80% of the convencional diagnostic nuclear imaging procedures and represent yearly approximately 30 million examinations/year worldwide a year in diagnostic tests in hospitals, among others by oncology, cardiology and neurology.The production of radiopharmaceuticals for use in Nuclear Medicine has a complex system. It involves carefully calculated production schedules that take into account supply, demand and many logistical operations.The aim of this study is to show how our nuclear medicine department manage the impact of the shortly 99Mo supply chain and consequently, in the 99mTc availability and other radiopharmaceuticals produced in nuclear reactora. Material(s) and Method(s): European nuclear medicine organizations had just pay attention to how the COVID-19 pandemic might affect different parts of the 99Mo supply chain when had to dealt again faced with a new problem;the shortness 99Mo production. There are only five nuclear reactors involved in the production of 99Mo on industrial scale. These aging reactors are subject to unscheduled shutdowns and longer maintenance periods making the 99Mo supply chain vulnerable. In the last few months at our nuclear medicine department we had to reinvent ourselves so as not to completely stop carrying out the previously scheduled exams and therapies. Result(s): The use of technetium generators in Europe represents about 17% - 25% of the worldwide consumption of 99Mo, representing 30,000 exams per day and about 1.1 million doses per month. The main consequences at the IPO-Porto was;Delays in diagnosis/staging, rescheduling exams, change of surgery dates (Sentinel Ganglion and Myocardial Perfusion Cardiacs), weeks of overbooking, delay in follow-up of Glomerular Filtration Rate in pre- or post-transplant patients, postponement of 131I Therapies, Scintigraphy and Whole Body Scintigraphy in patients who were already in hypothyroidism. we had to reinvent the use of 99mTc generators, change exams appointments times, reagroup exams types by defined days and other radiopharmaceutical management tools that were not commonly used. Conclusion(s): Approximately 2/3 of scheduled exams were postponed and we had to deal with weekly and daily stock updates. Our department suggest some measures and procedures that could help with future 99Mo shortages, in order to be ready in future situations and to avoid shortness of production: the creation of a centralized European radiopharmacy system, European policies to encourage long-term investment, homogenization of marketing specifications in the Member States, solid databases of radiopharmaceuticals used/ available in Europe and encouraging cooperation between other countries outside the European Union.

Unmasking of Immunoglobulin A Deposits Posttransplant due to COVID-19 AKI-Incidental or Causal - A Nephrologists' Dilemma A Case Report

COVID-19 is a global pandemic with the chronically immunosuppressed transplant recipients being the most vulnerable both to infection as well as complications of COVID-19. Here, we report a case of live-related renal allograft recipient who presented with complaints of loose stools and new-onset graft dysfunction 2 years posttransplant. He tested positive for COVID-19 infection. On allograft biopsy, there were significant immunoglobulin A (IgA) deposits with no evidence of rejection or ATN or crescents or significant chronicity. The initial pretransplant biopsy of the recipient had revealed chronic glomerulonephritis with nil deposits. The donor had no evidence of hematuria or hypertension and had a preserved GFR. We, therefore, considered the possibility of the unmasking of IgA deposits posttransplantation diagnosed in a recipient with COVID-19 infection. Copyright © 2022 Indian Journal of Transplantation.

The Impact of Arrhythmia on Prognosis in Hospitalized Covid-19 Patients. A Cardiac Telemetric Monitoring Study

Background: Cardiovascular abnormalities have been largely reported in patients with COVID-19. Among these, myocardial injury and rhythm disorders represent one of the most important complications in patients affected by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Moreover, a poorer prognosis has been documented in COVID-19 patients when complicated by arrhythmias, independently by age and sex. Objective(s): The aims of the present study were to identify some of non-cardiac and cardiac comorbidities and some myocardial electrical features (including QT dispersion) associated with arrhythmia in hospitalized COVID-19 patients. Moreover, another objective was to contribute in analyzing the impact of arrhythmias on outcome in this setting of patients. Method(s): At admission, each patient underwent cardiac telemetry monitoring through entire hospitalization period. In all the subjects, laboratory analyses, standard 12-lead electrocardiogram (both at admission and on discharge), and lung imaging examination (by means of both ultrasound scans and computed tomography) were performed. Patients exhibiting arrhythmia during in-hospital period were divided into three groups: i, with brady-arrhythmias;ii, with tachy-arrhythmias;and, iii, with tachy- and brady-arrhythmias. Result(s): Two-hundred patients completed the study (males, 123;mean age, 70.1 years);of these, 80 patients (40%) exhibited rhythm disorders on cardiac telemetry. Patients with arrhythmia resulted to be older (p<0.0001) than patients without arrhythmia. Moreover, patients with arrhythmia showed: i, greater number of comorbidities (p<0.0001);ii, higher values of creatinine (p=0.007), B-type natriuretic peptide (p<0.0001), troponin (p<0.0001), c-reactive protein (p=0.01), ferritin (p=0.001), d-dimer (p<0.0001), and procalcitonin (p=0.0008);iii, QT interval (p=0.002), QTc interval (p=0.04), and QTc dispersion (p=0.01);and, iiii, lower values of sodium (p=0.03), magnesium (p=0.04), glomerular filtration rate (p<0.0001), and hemoglobin (p=0.008) as compared to patients without arrhythmia. By comparing the three subgroups of patients, no significant differences were found. Multivariate analysis showed that age (OR=1.14 [95% CI: 1.07-1.22];p=0.0004), coronary artery disease (OR=12.7 [95% CI: 2.38-68.01];p=0.005), and circulating troponin (OR=1.05 [95% CI: 1.003-1.10];p=0.04) represented risk factors independently associated with arrhythmia. By analyzing allcause in-hospital mortality, it resulted a ~forty-fold higher among patients with arrhythmia (OR=39.66 [95% CI: 5.20-302.51];p=0.0004) when compared to patients without rhythm disorders. Conclusion(s): In the present study, arrhythmias have been to be associated with ageing, coronary artery disease, subtle myocardial injury, hyperinflammatory status, coagulative unbalance, and abnormalities in myocardial electrical impulse propagation in patients affected by SARS-CoV-2 infection. In alignment with previous reports, the presence of arrhythmia seems to be associated with a worse in-hospital prognosis. Given its usefulness, routinary use of cardiac telemetric monitoring should be encouraged in COVID wards.

Osmotic Demyelinating Syndrome and COVID-19

Introduction: Osmotic demyelination syndrome (ODS) is a dreaded complication of rapid sodium correction in high-risk hyponatremic patients. Predisposing factors include chronic alcoholism, malnourishment, severe hyponatremia. SARS-Cov2 infection may also be a risk factor as it is linked with multiple patterns of brain injury, renal damage and hyponatremia. Case Description: Patient is a 48-year-old female with history of alcohol use disorder who presented with malaise, vomiting, diarrhea for 3 days. On admission, the patient was stuporous and confused. She was clinically hypovolemic. Initial labs demonstrated severe hyponatremia (102 mmol/L), hypokalemia (2.2 mmol/L), HCO3 of 35mmol/L, lactic acid of 4 mmol/L, no EtOH, preserved GFR. SARS-CoV2 PCR was positive. She was not hypoxic, her chest X-ray was clear. The patient was resuscitated with 1L of isotonic saline, potassium correction was attempted. Her bloodwork 4 hours later showed Na of 113 mmol/L and K of 2.4 mmol/L. At this point patient had prominent diuresis, UNa was 13mmol/L, Uosm 175mOsm/kg and U spec gravity 1.006. Immediately DDAVP and D5W were started. She had a poor response to this therapy and her sodium continued raising even at maximal doses. At 24h her sodium was 118 mmol/L and at 48h it was 125mmol/L with stabilization at this level. She had clinical improvement and was more responsive on day 3. On the following days, sodium gradually drifted toward 132 mmol/L. On day 5 she developing worsening mental status. She was found poorly responsive with fixed gaze, aphasia, minimally removing extremities from pain, able to blink when asked. Brain MRI revealed signal abnormalities in the central pons, bilateral thalami, caudate, basal ganglia, subinsular regions consistent with ODS. Intensive treatment was restarted with D5W and DDAVP. Na of 124mmol/L was achieved at 24h. Over the course of the following days, she had partial recovery. She was discharged to rehab, able to smile, move her head and partially move her extremities. Discussion(s): SARS-Cov2 causes hyponatremia through several mechanisms. Poor oral intake, gastrointestinal loses, kidney injury and SIADH have been described. All of them may occur at the same time and cause hypovolemic/euvolemic states with high ADH. Volume replacement rapidly shuts off the ADH drive predisposing patients to get sodium overcorrection.