Predictors of cardio-kidney complications and treatment failure in patients with chronic kidney disease and type 2 diabetes treated with SGLT2 inhibitors

Background Clinical practice guidelines recommend sodium-glucose co-transporter 2 inhibitors (SGLT2is) to mitigate adverse kidney and cardiovascular outcomes in patients with type 2 diabetes (T2D), including patients with comorbid chronic kidney disease (CKD), also referred to as diabetic kidney disease (DKD), who are at even higher risk. In this study, we sought to identify predictors of cardio-kidney events, cardio-kidney complications, and treatment failure (i.e., addition/initiation of a new T2D class, insulin, or discontinuation of SGLT2is) after new initiation of SGLT2is in patients with CKD and T2D (DKD). Methods In this retrospective cohort study, we identified adult patients with DKD who initiated SGLT2is between April 1, 2012, and June 30, 2019, in Optum claims data. Outcome rates per 1000 person-years (PY) are reported with 95% confidence intervals (CIs). Cox proportional hazards regression identified patient characteristics associated with each outcome. Results The study population consisted of 6389 initiators of SGLT2is. The rate of CV hospitalization was 26.0 (95% CI 21.6, 30.4) per 1000 PY. Baseline characteristics associated with higher risk of CV hospitalization included age, atrial fibrillation, peripheral vascular disease (PVD), and cancer. The rate of kidney hospitalization was 12.0 (95% CI 9.0, 15.0) per 1000 PY. The risk increased significantly with baseline evidence of heart failure, hyperkalemia, respiratory failure, depression, and use of loop diuretics. In total, 55.0% of all SGLT2i initiators discontinued treatment during the follow-up period. The rate of treatment failure was 510.5 (95% CI 492.9, 528.1) per 1000 PY. Analysis of key time-dependent SGLT2i-associated adverse events showed that experiencing diabetic ketoacidosis and volume depletion were associated with risk of treatment failure. Conclusions Our study demonstrated high rates of residual cardio-kidney outcomes and treatment failure in patients with DKD treated with SGLT2is. Patients with high baseline CV risk and the presence of certain conditions, such as atrial fibrillation, PVD, and heart failure, were at higher risk for cardio-kidney events. Further research is needed to assess the potential relationship between adverse events and SGLT2i treatment failure.

Ground plane and selective buried oxide based planar junctionless transistor

In this work, we demonstrate a ground plane (GP) based Selective Buried Oxide (SELBOX) Junctionless Transistor (JLT), named as GP-SELBOX-JLT. The use of GP and SELBOX in the proposed device reduces the electric field and enhances volume depletion in the channel, hence improves I ON/I OFF ratio and scalability. Using calibrated 2-D simulation, we have shown that proposed device exhibits better Short Channel Effect (SHE) immunity as compared to SOI-JLT. Therefore, the proposed GP-SELBOX-JLT can be scaled without degrading the performance in sub 20 nm regime. In addition, the ac study has shown that the cutoff frequency (f T) of GP-SELBOX-JLT is almost equal to conventional SOI-JLT.

999Impact of Heatwaves on use of health services (GP and Emergency department visits)

Background Heatwaves are associated with increases in mortality and morbidity (mostly hospitalisations). However, evidence regarding heatwave impacts on the use of frontline health-services such as general practitioner (GP) consultations and emergency department (ED) services is limited. This study quantified the impact of heatwaves on the use of GP and ED services in Adelaide. Methods Data on GP services (2011-2016) from the Medicare Benefits Schedule and ED visits (2013-2018) were obtained from the Australian Bureau of Statistics and the Department of Health, respectively. Heatwaves were defined using Excess Heat Factor. Using time-stratified case-crossover models, we modelled heatwave-severity (low, severe/extreme) against the use of GP and ED services in the warm-season (October-March). Effect estimates are reported as relative risks (RRs). Results Total GP visits decreased during low-intensity heatwaves and increased during severe/extreme heatwaves (RR 1.14; 95%CI: 1.13-1.15). The highest increases during severe/extreme heatwaves were observed for respiratory (RR 1.36; 95%CI: 1.27-1.45) and psychiatric services. While ED visits decreased overall during low-intensity and severe/extreme heatwaves, those due to heat-light disorders (RR 4.23; 95%CI: 2.98-6.00), volume depletion, and respiratory diseases increased during severe/extreme heatwaves. Conclusions There were significant increases in the use of GP and specific ED services during heatwaves in Adelaide. Further research is needed to identify the intrinsic and extrinsic vulnerability factors contributing to these increases in Adelaide and other Australian cities. Key messages Impacts of heatwaves extend beyond mortality to include frontline health-services (GP/EDs) that are already challenged. Evidence presented may assist policymakers for resource allocation and healthcare workforce capacity building.

Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association

Background Recently there has been increased interest in a possible association between mast cell activation (MCA) disorder and postural orthostatic tachycardia syndrome (POTS). This study examined the frequency with which symptoms and laboratory findings suggesting MCA disorder occurred in patients diagnosed with POTS. Methods and Results Data were obtained from patients in whom symptoms and orthostatic testing were consistent with a POTS diagnosis. Individuals with <4 months symptom duration, evident ongoing inflammatory disease, suspected volume depletion, or declined consent were excluded. All patients had typical POTS symptoms; some, however, had additional nonorthostatic complaints not usually associated with POTS. The latter patients underwent additional testing for known MCA biochemical mediators including prostaglandins, histamine, methylhistamine, and plasma tryptase. The study comprised 69 patients who met POTS diagnostic criteria. In 44 patients (44/69, 64%) additional nonorthostatic symptoms included migraine, allergic complaints, skin rash, or gastrointestinal symptoms. Of these 44 patients, 29 (66%) exhibited at least 1 laboratory abnormality suggesting MCA disorder, and 11/29 patients had 2 or more such abnormalities. Elevated prostaglandins (n=16) or plasma histamine markers (n=23) were the most frequent findings. Thus, 42% (29/69) of patients initially diagnosed with POTS exhibited both additional symptoms and at least 1 elevated biochemical marker suggesting MCA disorder. Conclusions Laboratory findings suggesting MCA disorder were relatively common in patients diagnosed with POTS and who present with additional nonorthostatic gastrointestinal, cutaneous, and allergic symptoms. While solitary abnormal laboratory findings are not definitive, they favor MCA disorder being considered in such cases.

Potential Contributors to Increased Pulmonary Embolism Hospitalizations During the COVID-19 Pandemic: Insights From the German-Wide Helios Hospital Network

Background: After the first COVID-19 infection wave, a constant increase of pulmonary embolism (PE) hospitalizations not linked with active PCR-confirmed COVID-19 was observed, but potential contributors to this observation are unclear. Therefore, we analyzed associations between changes in PE hospitalizations and (1) the incidence of non-COVID-19 pneumonia, (2) the use of computed tomography pulmonary angiography (CTPA), (3) volume depletion, and (4) preceding COVID-19 infection numbers in Germany.Methods: Claims data of Helios hospitals in Germany were used, and consecutive cases with a hospital admission between May 6 and December 15, 2020 (PE surplus period), were analyzed and compared to corresponding periods covering the same weeks in 2016–2019 (control period). We analyzed the number of PE cases in the target period with multivariable Poisson general linear mixed models (GLMM) including (a) cohorts of 2020 versus 2016–2019, (b) the number of cases with pneumonia, (c) CTPA, and (d) volume depletion and adjusted for age and sex. In order to associate the daily number of PE cases in 2020 with the number of preceding SARS-CoV-2 infections in Germany, we calculated the average number of daily infections (divided by 10,000) occurring between 14 up to 90 days with increasing window sizes before PE cases and modeled the data with Poisson regression.Results: There were 2,404 PE hospitalizations between May 6 and December 15, 2020, as opposed to 2,112–2,236 (total 8,717) in the corresponding 2016–2019 control periods (crude rate ratio [CRR] 1.10, 95% CI 1.05–1.15, P &lt; 0.01). With the use of multivariable Poisson GLMM adjusted for age, sex, and volume depletion, PE cases were significantly associated with the number of cases with pneumonia (CRR 1.09, 95% CI 1.07–1.10, P &lt; 0.01) and with CTPA (CRR 1.10, 95% CI 1.09–1.10, P &lt; 0.01). The increase of PE cases in 2020 compared with the control period remained significant (CRR 1.07, 95% CI 1.02–1.12, P &lt; 0.01) when controlling for those factors. In the 2020 cohort, the number of preceding average daily COVID-19 infections was associated with increased PE case incidence in all investigated windows, i.e., including preceding infections from 14 to 90 days. The best model (log likelihood −576) was with a window size of 4 days, i.e., average COVID-19 infections 14–17 days before PE hospitalization had a risk of 1.20 (95% CI 1.12–1.29, P &lt; 0.01).Conclusions: There is an increase in PE cases since early May 2020 compared to corresponding periods in 2016–2019. This surplus was significant even when controlling for changes in potential modulators such as demographics, volume depletion, non-COVID-19 pneumonia, CTPA use, and preceding COVID-19 infections. Future studies are needed (1) to investigate a potential causal link for increased risk of delayed PE with preceding SARS-CoV-2 infection and (2) to define optimal screening for SARS-CoV-2 in patients presenting with pneumonia and PE.

Contrast-induced nephropathy in a patient with type 2 diabetes and coronary artery disease: a case report

Contrast-induced nephropathy (CIN) is the impairment of kidney function defined as a serum creatinine increase of 25% or 44 µmol/L compared with baseline, usually occurring 24 to 48 hours after the use of intravenous contrast. Important risk factors for CIN include female sex, advanced age (>65 years), type 2 diabetes (T2D), kidney disease, advanced heart failure, and intravascular volume depletion. We herein present a male patient with T2D, moderately reduced renal function, no albuminuria, and a positive echocardiography stress test. He underwent percutaneous coronary intervention (PCI), and two drug-eluting stents (in the left anterior descending coronary artery) and three bare-metal stents (in the right coronary artery) were implanted. Despite adequate rehydration (0.9% intravenous NaCl with 8.4% sodium bicarbonate) before and after the procedures, he developed irreversible kidney injury after coronary angiography and PCI. This case report demonstrates the unpredictable clinical course of CIN. Patients with T2D are at high risk for the occurrence of CIN, so careful clinical assessment is recommended with global renal functional reserve evaluation.

Constitutional Symptoms

Some of these are well known to produce distress but others are not as commonly thought of as symptoms which require palliation. Fatigue is nearly ubiquitous at the end of life and in all serious illness patients. While it may not be as obvious as pain or vomiting, it can be just as debilitating. Anorexia is not usually difficult for the patient but can be very hard for family/caregivers to understand. Hiccoughs are obvious but when intractable or chronic are also very uncomfortable and may predispose to poor oral intake. Ascites causes a host of other symptoms uncluding dyspnea and often requires surgical intervention. Fever and sweating cause discomfort but may also contribute to volume depletion and electrolyte disturbances.

Intracranial subdural hemorrhage following closed neural tube defect repair: illustrative case

BACKGROUND Intracranial subdural hematomas (SDHs) due to intracranial hypotension after pediatric spine surgeries are an uncommon pathology. Such findings have typically been associated with intraoperative durotomies that are complicated by a subsequent cerebrospinal fluid (CSF) leak. OBSERVATIONS The patient is a 17-year-old boy with a complex past medical history who received an uncomplicated S1–2 laminectomy for repair of his closed neural tube defect (CNTD), cord untethering, and resection of a lipomatous malformation. He returned to the hospital with consistent headaches and a 2-day history of intermittent left-sided weakness. Imaging demonstrated multiple subdural collections without a surgical site pseudomeningocele. LESSONS The case was unique because there have been no documented cases of acute intracranial SDH after CNTD repair. There was no CSF leak, and spine imaging did not demonstrate any evidence of pseudomeningocele. The authors believed that intraoperative CSF loss may have created enough volume depletion to cause tearing of bridging veins. In younger adolescents, it is possible that an even smaller volume may cause similar effects. Additionally, the authors’ case involved resection of the lipomatous malformation and an expansile duraplasty. Hypothetically, both can increase the lumbar cisternal compartment, which can collect a larger amount of CSF with gravity, despite no pseudomeningocele being present.

ENDOCRINOLOGY IN THE TIME OF COVID-19 - 2021 updates: The Management of Diabetes insipidus and Hyponatraemia

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counseling, with relevance for patients with diabetes insipidus (DI) or hyponatremia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of postoperative SIAD. They should know hyponatraemia symptoms. Hyponatraemia in COVID-19 is common with a prevalence of 20 to 30% and is mostly due to SIAD or hypovolemia. It mirrors disease severity and is an early predictor for mortality. Hypernatraemia may also develop in COVID-19 patients, with a prevalence of 3-5%, especially in ICU, and derives from different multifactorial reasons, e.g. due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.