A case series of diabetic ketoacidosis associated with SGLT2 inhibitors

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly initiated as treatment for type 2 diabetes due to favourable cardiorenal characteristics. However, studies have identified an increased risk of diabetic ketoacidosis (DKA). We carried out a retrospective, case-based study at East and North Herts NHS Trust between February 2018 and December 2020. Fifteen cases of SGLT2i associated DKA were identified in people with presumed type 2 diabetes;33.3% were classed as euglycaemic DKA with a blood glucose of <11mmol/L. All cases were associated with a significant precipitating factor including diarrhoea, vomiting, reduced oral intake and sepsis. One case was related to COVID-19. Two people were subsequently found to have raised islet autoantibodies suggesting type 1 diabetes or latent autoimmune diabetes in adults. It is important that awareness of SGLT2i associated DKA is raised among users and health care practitioners, including the recognition of euglycaemic DKA. Sick day rules should be emphasised and reiterated at clinical encounters. Non-specialists in primary care, oncology and in perioperative settings should be empowered to advocate for temporary withdrawal and there should be readier access to blood ketone monitoring when required. When SGLT2i associated DKA occurs, due consideration should be given to evaluate the diabetes classification and investigate the circumstances of the event. Copyright © 2023 John Wiley & Sons.Copyright © 2023 John Wiley & Sons, Ltd.

Diagnosing gestational diabetes during the Covid-19 pandemic using HbA1c rather than oral glucose tolerance test (OGTT)

The Royal College of Obstetrics and Gynaecology advocated replacing OGTT with HbA1c for gestational diabetes (GDM) screening for women with risk factors during the Covid-19 pandemic. HbA1c >=48mmol/mol/random plasma glucose (RPG) >=11.1mmol/l at booking indicated diabetes, and 41-47mmol/ mol/9-11mmol/ l prediabetes or possible GDM. Testing was repeated at 26 weeks if normal previously, with HbA1c >=39mmol/mol, fasting PG >=5.6mmol/l, or RPG >=9mmol/l diagnostic for GDM. A) At her clinic booking visit at 10 weeks gestation, 36 year-old South Asian female had HbA1c 55mmol/mol/RPG 9.5mmol/l suggesting undiagnosed type 2 diabetes. Initially managed with dietary advice and home blood glucose monitoring, metformin was added when self-monitored glucose above pregnancy targets (fasting and pre-meal <5.3mmol/l or 1 h post meal <7.8mmol/l) but insulin was required later. Metformin and insulin were stopped after delivery at 38 weeks with HbA1c 50mmol/mol three months postpartum, supporting the earlier diagnosis of type 2 diabetes. B) 32 year-old White Caucasian female was screened for GDM on booking at 11 weeks as BMI 38 kg/m2. HbA1c 44mmol/mol and RPG 6.9mmol/l confirmed GDM which was managed by dietary/lifestyle changes with glucose and pregnancy targets achieved until 28 weeks when metformin added. Normal delivery at 40 weeks with HbA1c 40mmol/mol three months postpartum triggered advice on long-term dietary/lifestyle changes and annual HbA1c checks. HbA1c was useful during the pandemic but most centres reverted to OGTT for GDM screening due to a significant fall in diagnoses using HbA1c >=39mmol/mol at 26 weeks. But, HbA1c testing was advantageous at booking to diagnose type 2 diabetes earlier.

Case Series of Burkholderia Pseudomallei Causing Melioidosis (Pulmonary, Cerebral, and Splenic Abscess)

Burkholderia pseudomallei is soil saprophytic Gram-negative bacilli that cause a fatal disease called melioidosis. Melioidosis is capable of causing cutaneous infection and systemic infections in the respiratory tract, cardiovascular, gastrointestinal, urinary, skin and soft tissue, and musculoskeletal and central nervous systems. Here, we report rare forms of pulmonary, cerebral, and splenic abscess case series of melioidosis caused by B. pseudomallei. Imported cases have been reported among tourists, immigrants, and soldiers who returned from endemic areas. The acquisition of infection is through percutaneous, inhalation, and ingestion of contaminated water;person-to-person transmission is very rare. Melioidosis cases are primarily found in the rainfall season and are usually associated with risk factors such as diabetes, alcoholism, and chronic renal diseases. However, 20-26% of cases were not associated with predisposing conditions. The identification is based on colony morphology, Gram stain, antibiotic susceptibility testing, and other supportive automated and molecular assays when we suspect B. pseudomallei. There are two phases, the intensive and eradication phases, in managing melioidosis. In the intensive phase, ceftazidime for 2 weeks showed efficacy in almost 50% of cases, and the eradication phase treatment with co-trimoxazole and doxycycline or amoxicillin/clavulanic acid for 3-6 months showed an excellent response. The improper clinical diagnosis and management of B. pseudomallei can lead to complications. Hence, early diagnosis with microbiological approaches such as culture, biochemical reactions, or automated systems available and antimicrobial sensitivity testing will cure the patient quickly without mortality.Copyright © 2023 The Authors.

Complex presentations in people with diabetes: Does HbA1c help or hinder?

HbA1c measurement is widely used for diagnosis/ management/remission of diabetes with international schemes certifying comparability. A) 75 year-old Chinese female with type 2 diabetes was admitted in April 2020 with Covid-19 and diabetic ketoacidosis. Glucose was 35mmol/l and HbA1c 150mmol/mol with previous HbA1c of 45mmol/mol on metformin and alogliptin. She was treated for ketoacidosis and once-daily Lantus introduced along with supportive management of viral illness. B) 68 year-old Afro-Caribbean with type 2 diabetes on metformin before admission, presented with new onset, jerky ballistic movements of high amplitude in right arm, 10-15 movements every 5 min. Admission glucose was >33mmol/l, ketones 1.8mmol/l and HbA1c >217mmol/ mol. Hemichorea-hemiballism, a hyperglycaemia related movement was diagnosed and insulin commenced. Glucose decreased to 8-20mmol/ l, reaching 5-15mmol/ l by time of discharge. Ballistic movements resolved when glycaemic control improved with HbA1c 169mmol/mol, 25 days after discharge. C) Several days before admission, a female with diabetes over 20 years required attention from paramedics on four occasions for hypoglycaemia. Months beforehand metformin was replaced by gliclazide due to chronic kidney disease with HbA1c 50mmol/mol, and she was transfused six weeks before admission for microcytic anaemia. Gliclazide was discontinued and her diet modified which prevented further hypoglycaemic episodes. Variant haemoglobin, beta-thalassaemia which can overestimate glycaemia;undetected by HbA1c HPLC method, invalidated HbA1c as did the blood transfusion. These cases highlight that inadequate understanding of HbA1c can lead to acute presentations of dysglycaemia. As HbA1c accuracy can be affected by multiple factors, clinical assessment and triangulation are key to the management of such patients.

GDM diagnosis criteria: Standard and Covid-19 criteria

Aim: Standard diagnosis of gestational diabetes (GDM) is based on the Oral Glucose Tolerance test (OGTT). During the Covid-19 outbreak, due to Covid restrictions, criteria were modified i.e Fasting Blood Glucose >=5.3 and/ or HbA1c >= 39 for diagnosis of GDM. After the lifting of the Covid restrictions, the standard criteria were reimplemented and on analyzing the data, it was highlighted that some of the patients could have tested negative for GDM based on Covid Criteria. Method(s): We analyzed the data of 43 patients based on standard criteria (OGTT and HbA1c) after Covid restrictions, with the following results. Result(s): 11/43(28%) patients who were diagnosed on the basis of standard criteria could have been missed based on Covid criteria. Out of 11 deliveries, 2 babies with weight above 4 kg. There were no admissions to NICU. One patient had postpartum hemorrhage with 670 mL of blood loss. Conclusion(s): This was a retrospective study in which we analyzed the data of 45 pregnant females diagnosed with GDM based on testing using the Covid criteria and compared this to 43 pregnant females who were diagnosed with GDM on the basis of OGTT based on GOLD standard NICE criteria. In addition, we also examined maternal and obstetric outcomes in both groups such as the mode of delivery, the baby's birth weight, the incidence of shoulder dystocia, mean blood loss (MBL), and NICU admission. We understand that Covid GDM diagnosis was a necessity of time. In this study, we want to learn what could have been missed with that diagnostic criteria. For future pandemics, we need to revise our diagnostic criteria to avoid the risk of underdiagnosing GDM and associated complications.

Optimal continuous glucose monitoring metrics for identification of women with gestational diabetes

Aims: Continuous glucose monitoring (CGM) is widely used in pregnant women with pre-gestational diabetes, but optimal targets have not been defined in gestational diabetes. Previous work identified mild hyperglycaemia in pregnant women without gestational diabetes, but with risk factors such as obesity. We aimed to examine CGM metrics and patterns of glycaemia in women with gestational diabetes compared to healthy pregnant women with comparable risk factors. Method(s): We recruited 73 healthy women with >1 risk factor (gestational diabetes excluded using Covid-19 criteria, OGTT) and 200 women with gestational diabetes (NICE and interim-Covid- 19 criteria) from antenatal clinics at 28 weeks' gestation. A Dexcom G6 CGM device was cited on the non-dominant upper arm. Result(s): Women with gestational diabetes had significantly higher weight (mean +/- SEM 95.7 kg +/- 1.3 Vs 85.4 kg +/- 2.2) and BMI (36.0 +/- 0.5 Vs 31.3 +/- 0.7) compared to healthy pregnant women (p < 0.01). Women with gestational diabetes had significantly higher mean CGM-glucose (mean +/- SEM 5.6 +/- 0.01 Vs 5.4 +/- 0.01mmol/l;p < 0.01), significantly altered time-below- range (median(IQR);1.0% (0.2-2.9) vs 2.5% (0.7-5.5);p < 0.05) and time-in- range (95.0% (91.1-97.9) vs 94.5% (87.9-96.2);p < 0.05) but comparable time-above- range to healthy women with risk factors. Diurnal glucose profiles in women with gestational diabetes were comparable to healthy women between 14:00 and 18:00, but demonstrated significant increases in glucose at all other time points during the 24-h cycle (p < 0.01). Conclusion(s): Mean CGM glucose is the most reliable CGM metric to distinguish women with gestational diabetes from healthy pregnant women with risk factors.

Change in glycaemic control immediately after Covid-19 vaccination in people with type 1 diabetes: What happens after the most recent vaccination?

Aims: We have shown previously in 93 individuals with type 1 diabetes using the FreeStyle Libre flash glucose monitor that the week after their first Covid-19 vaccination, the percent 'time in target range 3.9-10mmol/ l' (%TTR) average went from 55.2%-> 52.4% (effect size -5.1%) with 58% of people recording a fall. 47 (50%) people with HbA1c < 56mmol/mol %TTR went from 69.3-> 63.5 (-8.3%) and 24 (25%) people using insulin+oral treatment 56.7%-> 50.7% (-10.1%). We have now repeated the exercise after the most recent Covid-19 vaccination. Method(s): FreeStyle Libre data and medical records of the same patients from the previous study were examined for the week before and week after their most recent Covid-19 vaccination. () in the results section show change in %TTR as % of the prior value to show effect size. TTR% results from 2 weeks before and after were also considered. Result(s): Median time between vaccines was 38 weeks IQR (37-40). After the latest vaccination average %TTR average went from 51.1%-> 49.8% (-2.5%) with a reduction found in 54% of patients. Impact on the 39 patients with HbA1c < 56mmol/mol -% TTR from 66.2%-> 61.8% (-6.5%) and the 20 (25%) patients using insulin+oral %TTR from 48.2%-> 47.1% (-2.2%). 65% of the patients whose %TTR fell previously, fell again after this vaccination. Fortnight average %TTR 53.5%-> 52.1% (-2.7%) whereas in the previous study across fortnight %TTR 55.4%-> 54.0% (-2.4%). Conclusion(s): The perturbation effect on blood glucose with 1st Covid-19 vaccination was seen again in the latest vaccination but reduced in magnitude, confirming that a significant group of type 1 diabetes individuals' glycaemic control is still being impacted by the Covid-19 vaccination.

Comparative effectiveness and safety of a pharmacist-managed protocol for the transition from intravenous to subcutaneous insulin

Purpose: To evaluate the effectiveness and safety of a pharmacist-managed protocol for transitioning critically ill patients from intravenous (iv) to subcutaneous insulin compared with a provider-managed process. Method(s): This single-center, retrospective, observational study included patients admitted to the medical or surgical/trauma intensive care unit who received a continuous infusion of iv insulin from January 2019 to April 2021. Patients were excluded if they were less than 18 years of age, pregnant, incarcerated, or received iv insulin for the diagnosis of diabetic ketoacidosis, hyperglycemic hyperosmolar state, calcium channel blocker or beta blocker overdose, or hypertriglyceridemia. The primary outcome was the percentage of blood glucose (BG) concentrations within the target range of 70-150 mg/dL from 0 to 48 h following transition to subcutaneous insulin. Secondary outcomes included percentage of BG concentrations within goal range following transition at 0-12 h and 12-24 h, incidence of hypo- and hyperglycemia, and percentage of patients requiring dose adjustments after initial transition. Result(s): A total of 110 unique patients were included with 70 patients in the provider-managed group and 40 patients in the pharmacist-managed group. On average, pharmacists transitioned patients to 63% basal insulin based on their 24-h total day dose of insulin. The pharmacist-managed group achieved glycemic control in 53% of transitions at 12 h, 40% at 24 h, and 47% from 0 to 48 h, while the provider group achieved glycemic control in 25% of transitions at 12 h, 12% at 24 h, and 18% from 0 to 48 h (p < 0.001 for all time points). As for safety end points, the pharmacist-managed group demonstrated lower rates of hypoglycemia (p = 0.001), severe hypoglycemia (p = 0.332), hyperglycemia (p < 0.001), and severe hyperglycemia (p < 0.001) compared with the provider-managed group. Conclusion(s): Pharmacists can effectively and safely transition critically ill patients from iv to subcutaneous insulin utilizing a standardized protocol.Copyright © 2023 Pharmacotherapy Publications, Inc.

Was the diagnosis of gestational diabetes from 34 weeks gestation of pregnancy more prevalent during Covid-19 due to the change in how gestational diabetes was diagnosed?

Aim: During Covid we noticed that more women were being diagnosed with Gestational Diabetes (GDM) from 34 weeks gestation than prior to Covid. It was suspected that this was due to how GDM was diagnosed, from Oral Glucose Tolerance Test (OGTT) prior to Covid to HbA1c with Fasting or Random Blood Glucose (RBG) during Covid. Method(s): An audit of our GDM database was performed, looking at rates of late GDM diagnosis from 2018-present. Result(s): Prior to Covid the late diagnosis rate was 14-15%. In 2020 and 2021 this increased to 27.7%. This year diagnosis is only by OGTT, and the rate has dropped to 21%. There was also a significant rise in the number of women who were being diagnosed from 34 weeks gestation whom had previously been tested for GDM earlier in their pregnancy. In 2018 and 2019 52-56% of these women had previously been tested. In 2020 this increased up to 84% and fell to 74% in 2021. This year the rate has fallen to 67%. In 2018 and 2019 all women had been diagnosed using OGTT's. In 2020 61% of women had previously been tested for GDM by HbA1c and RBG, with this increasing to 84% in 2021. This year only 10% had previously been tested using HbA1 and RBG. Conclusion(s): The sharp increase in late diagnosis of GDM during the Covid seems to be related to the change in diagnostic testing and shows that OGTT is the more accurate way to diagnose GDM and not HbA1c with RBG.

Sars cov-2 infection in a neonate in ghana: A case report

Backgrounds: The clinical and socioeconomic effects of COVID-19 are still being felt through-out the world. The disease affects people of all age groups, but it is known to have a milder clinical course in children including neonates. There is paucity of data from Sub-Saharan Africa on neonatal COVID-19 infection, and no such case has been reported in the literature in Ghana. Case presentation: This study presented a case report of a neonate who was found to be positive for COVID-19 infection after presenting symptoms such as respiratory distress, rhinorrhoea, and cough. This neonate was managed with in-hospital standard protocol for sepsis with a focus on pneumonia. Conclusion(s): The national guidelines on COVID-19 management were used for the neonate who was recovered and discharged.Copyright © 2021, TMU Press.

Assessment of the Relationship between COVID-19 infection and Glucose Levels in Related to ABO Group Among Diabetes Patients in Iraq

COV-19 has been quickly spreading in the world, producing lung inflammation and abrupt, even deadly, pulmonary collapse, COV-19were much higher in diabetic patients than in non-diabetic pa-tients. Diabetes is one of the primary causes of illness and death, and its prevalence is projected to increase rapidly over the next several decades. This investigation sought to determine how COVID-19 influenced the levels of glucose in the blood of patients diagnosed with type 1 and type 2 diabetes (DM), as well as whether or not the levels of glucose returned to normal following a recovery period of one month. Addi-tionally, there was a connection between ABO blood type and the severity of COV-19. The current study was to how COV-19 affected ABO group distribution and blood glucose levels in people who suffer from type 1 and 2 diabetes (DM). Study design: This study included ninety (90) patient divided into three groups: diabetes patient group (30) sample (control), 30 sample of DM with COV-19group and 30 sample recovery from Covid 19 after period one month of recovery, determination of the above mentioned blood groups was performed using manual method, and glucose levels measured of DM by diabetes device. The study demonstrated a relation between blood type ABO and COV-19, with type B blood being the most influenced by COV-19 in patients with type 2 diabetes, whereas there were no significant variations between blood types in those who suffer from type 1 diabetes. In type 1, 2 diabetic patients, no significant differences in blood glucose levels were found between diabetic patients with COV-19 and the recovery group from COV-19. The study displayed that the severity of COV-19 disease associated with B blood type in patients who suffer from type 2 diabetes and Cov-19 has no direct impact on blood glucose levels.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

COVID-19 among Hospitalized Patients with Diabetes in Karachi: A Single Centre Study

Aim: To evaluate the clinical characteristics, severity, and outcomes of local COVID-19 patients with diabetes. Study Design: Case series Place and duration of study: Orthopedic Medical Institute Hospital, Karachi from 1st September 2020 to 28th February 2021. Method(s): One hundred and forty seven COVID-19 positive patients with diabetes and pre-diabetes were enrolled. The patients' demographic and clinical information specific to COVID-19 and diabetes was collected and analyzed. Result(s): The mean age of 64.03+/-11.56 years. The ischemic heart disease (39.9%) and hypertension (74.3%) were the two most prevalent comorbid conditions. The overall mortality rate of 20.3%. Between patients with diabetes receiving steroids and those receiving no steroids, the mean fasting (FBG) and random blood glucose (RBG) were relatively elevated. Glycemic control had no discernible impact on the severity, results, or length of the COVID-19 hospital stay (p>0.05). Conclusion(s): No significant effect of diabetes millitus control on COVID severity and outcomes, but the altered blood glucose levels suggest a need to define specific targeted intervention for COVID-19 patients with comorbidities, specifically diabetes mellitus.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Arterial Hypertension and Severe COVID-19 in Hospitalized Patients: Data from a Cohort Study

Aim. To assess the association of hypertension with the severe forms and fatal outcomes of Coronavirus disease 2019 (COVID-19). Material and Methods. This retrospective cohort study involved adult patients (>=18 years old), admitted to the University hospital 4 of Sechenov University (Moscow, Russia) between 08 April 2020 and 19 November 2020 with clinically diagnosed or laboratory-confirmed COVID-19. The cohort included 1637 patients. The primary outcome was all-cause in-hospital mortality. The secondary outcomes included intensive care unit admission (ICU) and invasive ventilation. Multiple logistic regression was performed to assess the independent association between risk factors and endpoints. Results. A total of 1637 patients were included in the study. 51.80% (n=848) of the subjects were males. The median age was 59.0 (48.0;70.0) years and 55.90% (n=915) had pre-existing diagnosis of hypertension. Patients with hypertension had significantly more severe lung injury based on chest CT scan findings as well as lower oxygen saturation (SpO2). More of them were admitted to ICU and placed on invasive ventilation. The hypertension group also had higher mortality. Age, hypertension, glucose, C-reactive protein and decreased platelet count were independently associated with mortality, hypertension having the strongest association (OR 1.827, 95% CI 1.174-2.846, p=0.008). Age, hypertension, neutrophil count, platelet count, glucose, and CRP were independently associated with ICU admission, with hypertension having the strongest association (OR 1.595, 95% CI 1.178-2.158, p=0.002). Age, hypertension, glucose, CRP and decreased platelet count were independently associated with invasive ventilation, with hypertension having the strongest association (OR 1.703, 95% CI 1.151-2.519, p=0.008).Based on the multiple logistic regression models, odds of death, ICU admission, and invasive ventilation were higher in the hypertension group as compared to the group without hypertension. Conclusion. Hypertension can be an independent predictor of severe COVID-19 and adverse outcomes, namely death, ICU admission, and invasive ventilation in hospitalized patients.Copyright © 2023 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.

Evaluation of Factors Causing a Delay in Management and Hospital Stay in Diabetic Foot Amputation Patients: A Prospective Cohort Study

OBJECTIVE: To determine the rate of different amputation levels in diabetic foot patients and the incidence of repetitive foot surgeries and evaluate the factors causing a delay in hospital stay and amputation of patients. METHODOLOGY: This prospective cohort study was conducted in Dr. Ruth K.M. Pfau, Civil Hospital Karachi, Pakistan. The study selected 375 participants from the clinic's daily patient inflow from October 2021 to March 2022 using a non-probability consecutive sampling technique. Those who had a delay in hospital stay and amputation were further followed up from May-October 2022. The chi-square test and Kruskal Wallis test (p-value <0.05) were used to correlate the effect of the level of lower limb amputation and the cause of delay in amputation using SPSS version 24.0. RESULT(S): Total 246(65.60%) were males and 129(34.40%) were females. Toe amputation was the most commonly seen amputation in 173(46.1%) participants. About 168(44.8%) patients had some in-hospital delay stay during their treatment. Preoperative hurdles (Uncontrolled RBS, Osteomyelitis, etc.) were the most common factor causing an in-hospital delay in 92(24.5%) patients. The level of amputation performed was found to be statistically significant with factors causing a delay in hospital stay through chi-square (p=0.003*) and Kruskal Wallis test H (2) statistic= 13.3, df = 3, H (2), P=0.004*). CONCLUSION(S): Diabetic foot is a frequent cause of amputation globally, majorly in developing countries like Pakistan. On-time provision of treatment to these patients can decline the global amputation rate due to diabetic foot ulcers.Copyright © 2023 Syeda Anjala Tahir.

The First Reported Case of Lorlatinib-Associated Diabetic Ketoacidosis

Introduction: Lorlatinib is a third-generation tyrosine kinase inhibitor that inhibits anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1). Although 2-10% of patients with non-small cell lung cancer developed hyperglycemia in phase 2 and 3 studies of lorlatinib, only one case has subsequently reported hyperglycemia >500 mg/dL, and no cases of diabetic ketoacidosis (DKA) have been previously reported. Phase 1 trials in neuroblastoma are ongoing. Case Description: A 34-year-old woman with ALK-mutated paraspinal neuroblastoma presented with DKA 14 months after initiation of lorlatinib. Prior to starting lorlatinib, her hemoglobin A1c had been 5.0% (n: < 5.7%). After 12 months of therapy, her A1c increased to 7.8%, prompting the initiation of metformin 500 mg daily. However, two months later she was admitted for DKA with a blood glucose of 591 mg/dL (n: 65-99 mg/dL), CO2 17 mmol/L (n: 20-30 mmol/L), anion gap 18 (n: 8-12), moderate serum ketones, and 3+ ketonuria. Her A1c was 14.8%, C-peptide was 1.2 ng/mL (n: 1.1-4.3 ng/mL), and her glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies were negative. She was also found to be incidentally positive for COVID-19 but was asymptomatic without any oxygen requirement. The patient's DKA was successfully treated with IV insulin infusion, and she was discharged after 3 days with insulin glargine 27 units twice daily and insulin aspart 16 units with meals. One month later, her hemoglobin A1c had improved to 9.4%, and the patient's oncologist discontinued lorlatinib due to sustained remission of her neuroblastoma and her complication of DKA. After stopping lorlatinib, her blood glucose rapidly improved, and she self-discontinued all her insulin in the following 3 weeks. One month later, she was seen in endocrine clinic only taking metformin 500 mg twice daily with fasting and post-prandial blood glucose ranging 86-107 mg/dL. Discussion(s): This is the first reported case of DKA associated with lorlatinib. This case highlights the importance of close glucose monitoring and the risk of severe hyperglycemia and DKA while on lorlatinib therapy. Discontinuation of lorlatinib results in rapid improvement of glycemic control, and glucose-lowering treatments should be promptly deescalated to avoid hypoglycemia.Copyright © 2023

Functional outcome in patients with ischemic stroke and COVID-19 in Lima, Peru

Introduction: COVID-19 seems to induce ischemic stroke by several potential mechanisms including promoting hypercoagulability, and worse functional outcomes have been reported in patients with stroke and the infection with SARS-CoV-2. Objective(s): Determine the association between functional outcome and COVID-19 in patients with stroke. Patients and Methods: We performed a case control study comparing patients admitted to a neurological reference center in Peru with a diagnosis of stroke before (controls) and after (cases) the onset of the COVID-19 pandemic. There were 31 cases diagnosed with COVID-19 and 62 controls without COVID-19. Bivariate analysis and conditional fixed-effects Poisson regression analysis were used to evaluate the association between the functional outcome of the stroke and COVID-19. Result(s): Cases had higher baseline serum glucose (133.5, IQR: 117.5-174 versus 117, IQR: 101-130, p = 0.033) than controls, higher neutrophil counts (7.91, IQR: 5.93-9.57 versus 5.96, IQR: 4.41-7.79, p = 0.008), lower lymphocyte counts (1.48, IQR: 1.04-1.8 versus 1.83, IQR: 1.26-2.32, p = 0.025), higher neutrophil/lymphocyte ratios (5.44, IQR: 4.0-8.1 versus 3.29, IQR: 2.25-6.02, p = 0.011), higher NIH stroke scale/score (NIHSS) (14, IQR: 9-18 versus 7 IQR: 5-11, p = 0.000), and higher modified Rankin scores at discharge (4, IQR: 4-5 versus 2, IQR: 1-4), p = 0.001). Seven (21.88%) participants died in the group of cases versus 1 (1.56%) in the controls (p = 0.014). The odds ratio of having a bad functional outcome at discharge was 1.344 (CI: 1.079-4.039;p = 0.029), adjusted by NIHSS at admission. Conclusion(s): Our findings suggest that ischemic strokes associated with COVID-19 are more severe, have worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.Copyright © 2023 Sociedad Neurologica Argentina

Fungal pneumonia in COVID-19 patients: Risk factors and early prediction

Objective To determine the risk factors for developing secondary fungal pneumonia in moderate to severe coronavirus disease 2019 (COVID-19) cases. Using predictors of fungal infection helps to guide the diagnosis and treatment in these cases and save their lives. Patients and methods A total of 257 patients with moderate to severe COVID-19 pneumonia were examined in this retrospective study at Al Qassimi Hospital of EHS. An assessment of clinical, laboratory, and radiologic findings was performed upon admission. The data were collected and analyzed. Results Overall, 32% of critically ill COVID cases had fungal infection;47% of them were candida, whereas aspergillosis and yeast were positive in 26.5% each. At the time of hospitalization, computed tomography chest findings had a strong correlation with fungal culture results in COVID-19 cases. Fungal infection in COVID-19 cases correlated strongly with metabolic acidosis, high erythrocyte sedimentation rate, high blood sugar, need for mechanical ventilation at admission, vasopressor use, renal replacement, long duration of steroid treatment, long stay in ICU, and long duration on mechanical ventilation. The longer the duration of PCR positivity, the higher the incidence of positive sputum fungal culture result. Conclusion COVID-19-infected patients with other risk factors for fungal infections should always be considered to have fungal infections if pathogenic organisms are isolated from respiratory secretions or other microbiological or immunological markers appear positive. Computed tomography chest finding in COVID-19 cases is an important predictor for fungal infection.Copyright © 2023 The Egyptian Journal of Chest Diseases and Tuberculosis.

Hyperglycemia and Hypoglycemia Contributions to Acute Respiratory Distress Syndrome

Purpose of Study Non-diabetic COVID-19 patients with elevated admission fasting blood glucose levels ('hyperglycemia') inexplicably have an increased 28 day mortality and higher inhospital complications including the Acute Respiratory Distress Syndrome (ARDS) but potentially contributing blood glucose changes during ARDS development were not reported (Wang S et al: Diabetologia 2020). Our goal was to determine blood glucose alterations before and during acute lung injury development in a rat model used to study ARDS. Methods Used We sequentially evaluated blood glucose levels for 24 hours and lung lavage protein levels (lung permeability) and lung lavage neutrophil numbers (lung inflammation) at 24 hours to assess acute lung injury ('ARDS') in young (~3 month) and old (~12 month) control and a novel strain of hyperoxia surviving 'resistant' rats before and after administering high and low insulin doses and before and after interleukin- 1/lipopolysaccharide (IL-1/LPS) insufflation. Summary of Results Glucose levels increase rapidly and sequentially in young control, but not young resistant, rats peaking ~2 hours after insufflation. Glucose levels also increase in old control and old resistant rats after insufflation compared to young control and young resistant rats after insufflation. The pattern of glucose levels at 2 hours after insufflation resembles lung lavage proteins and neutrophils at 24 h after insufflation (table 1). Administering high insulin (High In) doses decreases glucose levels ('hypoglycemia') and worsens ARDS while administering low insulin (Low In) doses correct glucose levels and improve ARDS. Conclusions Hyperglycemia develops in both young and old rats developing ARDS and high or low glucose levels parallel worse acute lung inflammation and acute lung injury ('ARDS'). Controlling glucose judiciously with insulin may be beneficial in combatting ARDS caused by SARS-CoV-2 infection and other insults.

Effect of telehealth-based versus in-person nutritional and exercise intervention on type II diabetes mellitus improvement and efficiency of human resources utilization in patients with obesity

Aims: Telehealth became a patient necessity during the COVID pandemic and evolved into a patient preference in the post-COVID era. This study compared the % total body weight loss (%TBWL), HbA1c reduction, and resource utilization among patients with obesity and diabetes who participated in lifestyle interventions with or without telehealth. Method(s): A total of 150 patients with obesity and diabetes who were followed every 4-6 weeks either in-person (n = 83) or via telehealth (n = 67), were included. All patients were provided with an individualized nutritional plan that included a weight-based daily protein intake from protein supplements and food, an activity/sleep schedule-based meal times, and an aerobic exercise goal of a 2000-calorie burn/week, customized to patient's preferences, physical abilities, and comorbidities. The goal was to lose 10%TBWL. Telehealth-based follow-up required transmission via texting of weekly body composition measurements and any blood glucose levels below 100 mg/dl for medication adjustments. Weight, BMI, %TBWL, HbA1c (%), and medication effect score (MES) were compared. Patient no-show rates, number of visits, program duration, and drop-out rate were used to assess resource utilization based on cumulative staff and provider time spent (CSPTS), provider lost time (PLT) and patient spent time (PST). Result(s): Mean age was 47.2 +/- 10.6 years and 74.6% were women. Mean Body Mass Index (BMI) decreased from 44.1 +/- 7.7-39.7 +/- 6.7 kg/m2 (p < 0.0001). Mean program duration was 189.4 +/- 169.3 days. An HbA1c% unit decline of 1.3 +/- 1.5 was achieved with a 10.1 +/- 5.1%TBWL. Diabetes was cured in 16% (24/150) of patients. %TBWL was similar in regards to telehealth or in-person appointments (10.6% +/- 5.1 vs. 9.6% +/- 4.9, p = 0.14). Age, initial BMI, MES, %TBWL, and baseline HbA1c had a significant independent effect on HbA1c reduction (p < 0.0001). Program duration was longer for in-person follow-up (213.8 +/- 194 vs. 159.3 +/- 127, p = 0.019). The mean annual telehealth and in-person no-show rates were 2.7% and 11.2%, respectively (p < 0.0001). Mean number of visits (5.7 +/- 3.0 vs. 8.6 +/- 5.1) and drop-out rates (16.49% vs. 25.83%) were lower in telehealth group (p < 0.0001). The CSPTS (440.4 +/- 267.5 min vs. 200.6 +/- 110.8 min), PLT (28.9 +/- 17.5 min vs. 3.1 +/- 1.6 min), and PST (1033 +/- 628 min vs. 113.7 +/- 61.4 min) were significantly longer (p < 0.0001) for the in-person group. Conclusion(s): Telehealth offered comparable %TBWL and HbA1c decline as in-person follow-up, but with a shorter follow-up, fewer appointments, and no-shows. If improved resource utilization is validated by other studies, telehealth should become the standard of care for the management of obesity and diabetes.Copyright © 2023 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.

Nonhuman Primate Model of Long Covid: Immune Insights of Glycometabolic Dysfunctions

Background: A major consequence of COVID-19 is long-term metabolic complications (metabolic PASC or Long COVID) following acute disease resolution leading to hyperglycemia, increased risk of diabetes or defects in glucose metabolism. However, the mechanisms underlying the links between COVID-19 and glycometabolic disruptions remain unclear. Method(s): 15 African green monkeys (AGM;Chlorocebus aethiops) were infected with SARS-CoV-2 (Wuhan stain) and divided into two groups: unvaccinated (n=10) and vaccinated (BNT162b2 (Pfizer) 4-days post infection;n=5). Subgenomic SARS-CoV-2 mRNA (sgRNA) reflecting active replication was quantified in nasal and pharyngeal swabs, and blood chemistry analysis was performed longitudinally up to 18 weeks post-infection. We quantified liver glycogen at necropsy using Periodic acid-Schiff staining. Finally, we longitudinally analyzed 96 plasma proteins using a proximity extension assay (Olink). STRING was used to identify enriched protein networks. Comparisons between the two groups over time were performed using PERMANOVA. Result(s): All animals had detectable sgRNA ( >3.64x106) at day 3, and only two were undetectable at week 5. Post-infection BNT162b2 vaccination partially inhibited the SARS-CoV-2 mediated disruption of glucose levels (P=0.001, Fig. 1A). Liver glycogen levels following necropsy correlated positively with blood glucose levels at week 12 (r=0.74, P =0.003). Histopathological analysis revealed no marked evidence of long-term inflammation or fibrosis of pancreatic islets. Using the plasma proteomic data, we identified a signature of 15 SARS-CoV-2-modulated plasma proteins coinciding with early onset hyperglycemia during acute infection (P=0.001, Fig. 1B). These proteins are enriched for biological processes linked to chemotaxis (FDR=1.38E-06), and viral protein interaction with cytokines (FDR=1.01E-12) (Fig. 1C). Of these, CCL25 and glial cell derived neurotrophic factor (GDNF) remained persistently elevated post-acute infection and correlated with blood glucose levels (r=0.57, P=0.0003;and r=0.64, P<0.0001, respectively, Fig. 1D). Conclusion(s): Our AGM model validates phenotypes of metabolic PASC and offers an opportunity to mechanistically study the manifestations of PASC. Our preliminary data suggest that vaccine-preventable early insults by metabolicregulating immune factors may contribute to long-term dysregulated liver and systemic glucose homeostasis during PASC. These immune factors warrant further investigation for their mechanistic links to PASC. (Figure Presented).