Baseline History Research Articles

421-P: Differential Prognostic Burden of Lower-Limb Amputation and Cardiovascular Disease on the Risk of All-Cause Death in People with Type 1 Diabetes

Background: Nontraumatic lower-limb amputation (LLA) and cardiovascular disease (CVD) both result in reduced life expectancy in patients with type 1 diabetes, but the differential burden between these conditions is unknown. We compared the effects of LLA and CVD on the risk of all-cause death in people with type 1 diabetes. Methods: We used pooled data from the SURGENE, GENEDIAB, and GENESIS prospective cohorts. Data were divided into: 1) absence of CVD (myocardial infarction and/or stroke) nor LLA, 2) history of CVD alone without LLA, 3) LLA alone without CVD or 4) CVD and LLA at baseline. Participants with baseline history of peripheral artery disease were excluded from groups 1 and 2. The study endpoint was all-cause death. Results: Among 1169 (male 55%, age 40 ± 13 years, diabetes duration 23 ± years) participants, LLA, CVD or 2 combined conditions were present at baseline in 62 (5.3%) , 49 (4.2%) and 20 (1.7%) subjects, respectively. All-cause death occurred in 3 (26%) subjects during 17-year follow-up. The risk of all-cause death increased in subjects withbaseline history of LLA (adjusted HR 2.26 [95% CI, 1.56 - 3.28], p<0.0001) or CVD (2.00 [1.34 - 3.01], p=0.0008) versus no condition, with an additive effect in those with two combined conditions (5.32 [3.14 - 9.00], p<0.0001) . No incremental risk of death was observed in people with CVD versus LLA (0.87 [0.54 - 1.41]) . Compared with no condition, LLA and CVD were similarly associated with reduced life expectancy during follow-up: 3.38 (95% CI, 1.87 -4.88) and 2.79 (1.26 - 4.32) years, respectively. Combined conditions expose to 7. (4.76 - 9.31) less years of life expectancy (all p<0.0001) . Conclusion: LLA and CVD conferred a similar and heavy burden regarding mortality in type 1 diabetes population. Our findings encourage a careful consideration of people with type 1 diabetes and LLA as it is usually done for those with CVD, in terms of management of risk factors, treatments and prevention. Disclosure M.Camoin: None. O.Bourron: Other Relationship; Novo Nordisk. A.Scheen: Advisory Panel; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. R.Roussel: None. M.Marre: Board Member; AstraZeneca, Consultant; Novo Nordisk. K.Mohammedi: Board Member; Lilly, Novo Nordisk, Sanofi, Research Support; Cyclerion Therapeutics, Inc., Speaker's Bureau; Abbott, AstraZeneca. G.Velho: None. P.Saulnier: Consultant; Grünenthal Group, Research Support; AstraZeneca, Novo Nordisk, Sanofi. L.Potier: Board Member; Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Consultant; AstraZeneca, Sanofi. Y.Abouleka: None. C.Carpentier: None. S.Dubois: None. A.Larroumet: Consultant; Lilly Diabetes, Novo Nordisk, Sanofi. V.Rigalleau: None.

The latest cutoff value of high-sensitivity cardiac troponin I (access hs-TnI) for major adverse cardiac events during the perioperative period of coronary artery bypass grafting: a retrospective study from a single heart center

Abstract Objectives To investigate the latest cutoff value of high-sensitivity cardiac troponin I for major adverse cardiac events (MACEs) during the perioperative period of coronary artery bypass grafting (CABG). Methods A total of 200 patients, into MACEs and non-MACEs groups according to the occurrence of MACEs over a 12 day postoperative period underwent a complete baseline history survey, physical examination, 12-lead electrocardiogram (ECG), and laboratory examination during a preoperative cardiology consultation. Serum levels of hs-TnI, myohemoglobin, creatine kinase MB isoform (CK-MB), and B-type natriuretic peptide were assessed using a Beckman DXI800 automatic chemiluminescence immune analyzer. Results The 200 patients were classified into the MACEs (n=10) and non-MACEs (n=190) groups. Based on a receiver-operating characteristic analysis, the optimal 4–6 h postoperative hs-TnI, CK-MB, and MYO joint cut-off levels for predicting perioperative MACEs were 2,622.3 pg/mL, 17.9 ng/mL, and 190.2 ng/mL, respectively. The AUC was 0.779 (95% confidence interval: 0.622–0.937; p<0.05) with a sensitivity of 80.0% and a specificity of 74.0%. When the hs-TnI, CK-MB, and MYO levels exceeded the joint cut-off levels, the incidence of MACEs was significantly increased during the perioperative period (Log rank p<0.05). Cox regression analysis showed that dyslipidemia, left ventricular ejection fraction <50%, hs-TnI level, and myohemoglobin level were the main risk factors for MACEs after CABG (p<0.05). Conclusion An hs-TnI level of 2,622.3 pg/mL, CK-MB level of 17.9 ng/mL, and MYO level of 190.2 ng/mL were the cutoff values for predicting MACEs. Dyslipidemia, left ventricular ejection fraction <50%, hs-TnI level, and myohemoglobin level were the main risk factors for MACEs after CABG.

0775 Impact of insomnia, depression and anxiety on adherence to upper airway stimulation for obstructive sleep apnea: ADHERE registry update

Abstract Introduction Insomnia, depression and anxiety are common comorbid conditions in patients with obstructive sleep apnea (OSA) and can negatively impact positive airway pressure (PAP) therapy adherence. Subsequent intolerance to PAP may lead to surgical treatment such as upper airway stimulation (UAS). We sought to determine the impact of baseline insomnia, anxiety or depression on UAS therapy adherence using data from a large multi-center registry. Methods The ADHERE registry collects information on patients undergoing UAS (Inspire Medical, Golden Valley, MN) including baseline history of insomnia, depression, anxiety and the Insomnia Severity Index (ISI) questionnaire. We determined overall prevalence of insomnia, depression and/or anxiety, as well as UAS adherence after 6 months of therapy in groups with insomnia, depression, anxiety or none of these conditions. Using ISI to quantify insomnia, adherence in patients with no/mild insomnia (ISI < 15) was compared to those with moderate/severe insomnia (ISI ≥ 15). Results 1639 patients were included; 10% reported a history of insomnia, 23% depression and 16% anxiety. There was no difference in UAS adherence between groups with or without a history of insomnia, depression, or anxiety. A baseline ISI score was available in 470 patients with no history of insomnia, and in 81 patients with a history of insomnia. In patients with no history of insomnia, 59% had ISI scores ≥15, while in those with a history of insomnia, 85% had ISI scores ≥15 (p < 0.001). There was no difference in therapy usage between patients with ISI scores <15 and ≥15 (6.7 ± 2.2 hours/night versus 6.4 ± 2.5 hours/night, p = 0.5). Conclusion This study examined the impact of insomnia, depression or anxiety on adherence to UAS therapy for OSA. Patients with and without these conditions had similar UAS adherence. We found that insomnia as objectively based on the ISI score may be underdiagnosed in UAS patients who have no subjective history of insomnia at baseline. Despite this, ISI severity did not impact UAS adherence. Longer term follow-up with serial ISI scores and adherence data is needed to further understand how insomnia severity impacts UAS therapy outcomes and usage. Support (If Any)

Association between hypertension and cutaneous melanoma, and the effect of aspirin: extended follow-up of a large randomised controlled trial

BackgroundThe association between hypertension and melanoma is unclear, and previous analyses of data from the ASPirin in Reducing Events in the Elderly (ASPREE) study demonstrated a reduced number of invasive melanoma events amongst aspirin-exposed hypertensive individuals. MethodsData from the ASPREE study which included (1) the intervention period with a median follow-up of 4.7 years, and (2) the observational period with an additional 2 years follow-up, were combined for this analysis. Logistic regression analyses examined the association between baseline hypertension and treatment status and past melanoma history. Survival analyses examined the association between hypertension and melanoma risk, and the effect of aspirin across hypertension groups. Cox proportional hazards models were used to compare incidence across groups. Results19,114 participants (median age of 74 years) were randomised to daily 100 mg aspirin or placebo. At baseline, hypertension and past melanoma history were recorded in 14,195 and 685 individuals, respectively. After adjustment for confounders, hypertension was significantly associated with past melanoma history (OR=1.34, 95%CI: 1.11–1.62). In a prospective analysis, baseline hypertension was not associated with melanoma risk. However, aspirin was associated with a reduced risk of incident melanoma amongst individuals with uncontrolled hypertension (blood pressure ≥140/90 mmHg; HR=0.63, 95%CI 0.44–0.89), but not in those with controlled hypertension (HR=1.04, 95%CI 0.74–1.46). ConclusionOur results support a reduced melanoma incidence amongst individuals with uncontrolled hypertension exposed to aspirin. Additional studies are required to confirm these findings.

Differential prognostic burden of cardiovascular disease and lower-limb amputation on the risk of all-cause death in people with long-standing type 1 diabetes

BackgroundCardiovascular disease (CVD) and nontraumatic lower-limb amputation (LLA) each results in reduced life expectancy in patients with type 1 diabetes, but the differential burden between these conditions is unknown. We compared the effects of CVD and LLA on the risk of mortality in people with type 1 diabetes.MethodsWe used pooled data from the SURGENE, GENEDIAB, and GENESIS prospective cohorts. Data were divided into: 1/absence of CVD (myocardial infarction and/or stroke) nor LLA, 2/history of CVD alone without LLA, 3/LLA alone without CVD or 4/both conditions at baseline. Participants with baseline history of peripheral artery disease were excluded from groups 1 and 2. The study endpoint was any death occurring during follow-up, regardless of the causes.ResultsAmong 1169 participants (male 55%, age 40 ± 13 years, diabetes duration 23 ± 11 years), CVD, LLA or both were present at baseline in 49 (4.2%), 62 (5.3%) and 20 (1.7%) subjects, respectively. All-cause death occurred in 304 (26%) participants during 17-year follow-up, corresponding to 18,426 person-years and an incidence rate of 16 (95%CI, 15–18) per 1000 person-years. The risk of death increased in individuals with baseline history of CVD (adjusted HR 2.00 [95% CI 1.34–3.01], p = 0.0008) or LLA (2.26 [1.56–3.28], p < 0.0001), versus no condition, with an additive effect in people with both conditions (5.32 [3.14–9.00], p < 0.0001). No incremental risk of death was observed in people with CVD versus LLA (0.87 [0.54–1.41]). Compared with no condition, CVD and LLA were similarly associated with reduced life expectancy during follow-up: 2.79 (95% CI 1.26–4.32) and 3.38 (1.87–4.88) years, respectively. Combined conditions expose to 7.04 (4.76–9.31) less years of life expectancy (all p < 0.0001).ConclusionsCVD and LLA conferred a similar burden regarding mortality in type 1 diabetes population. Our findings encourage a careful consideration of people with type 1 diabetes and LLA as usually recommended for those with CVD, in terms of management of risk factors, treatments and prevention.

Kidney Stone Events Following Parathyroidectomy vs Nonoperative Management for Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is associated with an increased risk of kidney stones. Few studies account for PHPT severity or stone risk when comparing stone events after parathyroidectomy vs nonoperative management. Compare the incidence of kidney stone events in PHPT patients treated with parathyroidectomy vs nonoperative management. Longitudinal cohort study with propensity score inverse probability weighting and multivariable Cox proportional hazards regression. Veterans Health Administration integrated health care system. A total of 44 978 patients with > 2 years follow-up after PHPT diagnosis (2000-2018); 5244 patients (11.7%) were treated with parathyroidectomy. Clinically significant kidney stone event. The cohort had a mean age of 66.0 years, was 87.8% male, and 66.4% White. Patients treated with parathyroidectomy had higher mean serum calcium (11.2 vs 10.8mg/dL) and were more likely to have a history of kidney stone events. Among patients with baseline history of kidney stones, the unadjusted incidence of ≥ 1 kidney stone event was 30.5% in patients managed with parathyroidectomy (mean follow-up, 5.6 years) compared with 18.0% in those managed nonoperatively (mean follow-up, 5.0 years). Patients treated with parathyroidectomy had a higher adjusted hazard of recurrent kidney stone events (hazard ratio [HR], 1.98; 95% CI, 1.56-2.51); however, this association declined over time (parathyroidectomy × time: HR, 0.80; 95% CI, 0.73-0.87). In this predominantly male cohort with PHPT, patients treated with parathyroidectomy continued to be at higher risk of kidney stone events in the immediate years after treatment than patients managed nonoperatively, although the adjusted risk of stone events declined with time, suggesting a benefit to surgical treatment.

Efficacy of Roxadustat on anemia and residual renal function in patients new to peritoneal dialysis

Background Both early correction of anemia and preserving residual renal function (RRF) are reported to improve patient survival. The aim of this study was to explore the efficacy and safety of Roxadustat for treatment of renal anemia in patients new to peritoneal dialysis (PD) and to assess its impact on RRF. Methods A retrospective analysis was performed on 60 initial peritoneal dialysis (PD) patients with renal anemia. Twenty-eight cases were treated with Roxadustat (Roxadustat group) and 32 with recombinant human erythropoietin (control group). Clinical characteristics, hemoglobin (Hb), C-reactive protein, blood lipids, iron metabolism, dialysis adequacy and RRF of the two groups were evaluated and adverse events were recorded. All patients were followed up for at least 40 weeks. Results After 40 weeks of treatment, mean Hb levels were significantly higher from baseline values in both groups, the mean Hb change in Roxadustat group was higher than control group (3.46 ± 1.59 g/dL vs. 2.28 ± 2.27 g/dL, p < 0.05). At 40 weeks, 92.9% patients met the target level of Hb in Roxadustat group and 84.4% in control group. Total iron binding was higher and ferritin was lower in Roxadustat group from baseline values and Roxadustat-induced Hb increases were independent of baseline C-reactive protein levels and history of rhuEPO administration. RRF decreased over time in both groups, the mean RRF change was lower in Roxadustat group than control group (1.15 ± 1.66 mL/min/1.73 m2 vs. 2.31 ± 1.46 mL/min/1.73 m2, p < 0.01). Compared with control group, patients in Roxadustat group had higher levels of total iron binding, 24 h urine volume, total weekly Ccr, and lower systolic pressure, ferritin, C-reactive protein, total cholesterol, LDL. No serious adverse reactions occurred in either group. Conclusion In patients new to PD, Roxadustat effectively and safely improved renal anemia and delay the decline of RRF.

Immune-Related Adverse Events After Immune Checkpoint Inhibitors for Melanoma Among Older Adults

Immune checkpoint inhibitors (ICIs) have improved survival in patients with advanced melanoma but can be associated with a spectrum of immune-related adverse events (AEs), including both autoimmune-related AEs and other immune-related inflammatory AEs. These associations have primarily been evaluated in clinical trials that include highly selected patients, with older adults often underrepresented. To evaluate the association between use of ICIs and immune-related AEs (autoimmune and other immune related) among older patients with cutaneous melanoma. A population-based cohort study was conducted from January 1, 2011, to December 31, 2015. Data were analyzed from January 31 to May 31, 2021. With use of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries, patients of White race diagnosed with stages II-IV or unknown (American Joint Committee on Cancer, AJCC Cancer Staging Manual 6th edition) first primary cutaneous melanoma during 2011-2015, as reported to SEER, and followed up through December 31, 2015, were identified. Immune checkpoint inhibitors for treatment of melanoma. The association between ICIs and immune-related AEs ascertained from Medicare claims data was estimated using multivariable Cox regression with hazard ratios (HRs) and 95% CIs and with cumulative incidence accounting for competing risk of death. The study included 4489 patients of White race with first primary melanoma (3002 men [66.9%]; median age, 74.9 [range, 66.0-84.9] years). During follow-up (median, 1.4 [range, 0-5.0] years), 1576 patients (35.1%) had an immune-related AE on a Medicare claim. Use of ICIs (reported for 418 patients) was associated with autoimmune-related AEs (HR, 2.5; 95% CI, 1.6-4.0), including primary adrenal insufficiency (HR, 9.9; 95% CI, 4.5-21.5) and ulcerative colitis (HR, 8.6; 95% CI, 2.8-26.3). Immune checkpoint inhibitors also were associated with other immune-related AEs (HR, 2.2; 95% CI, 1.7-2.8), including Cushing syndrome (HR, 11.8; 95% CI, 1.4-97.2), hyperthyroidism (HR, 6.3; 95% CI, 2.0-19.5), hypothyroidism (HR, 3.8; 95% CI, 2.4-6.1), hypopituitarism (HR, 19.8; 95% CI, 5.4-72.9), other pituitary gland disorders (HR, 6.0; 95% CI, 1.2-30.2), diarrhea (HR, 3.5; 95% CI, 2.5-4.9), and sepsis or septicemia (HR, 2.2; 95% CI, 1.4-3.3). Most associations were pronounced within 6 months following the first ICI claim and comparable with or without a baseline history of autoimmune disease. The cumulative incidence at 6 months following the first ICI claim was 13.7% (95% CI, 9.7%-18.3%) for autoimmune-related AEs and 46.8% (95% CI, 40.7%-52.7%) for other immune-related AEs. In this cohort study of older adults with melanoma, ICIs were associated with autoimmune-related AEs and other immune-related AEs. Although some findings were consistent with clinical trials of ICIs, others warrant further investigation. As ICI use continues to expand rapidly, ongoing investigation of the spectrum of immune-related AEs may optimize management of disease in patients.

Bisphosphonates and bone mineral density in patients with end-stage kidney disease and renal transplants: A 15-year single-centre experience

Chronic Kidney Disease Stage 5 (CKD-5) imparts a 4-fold increase in minimal trauma fracture with a substantial increase in mortality following hip fracture. Bone disease in CKD is complex, characterised by abnormal levels of PTH, calcium, phosphate, ALP, and vitamin D, manifesting as a condition known as CKD-Mineral and Bone Disorder (CKD-MBD). While bisphosphonates (BPs) are widely used in the management of osteoporosis, their therapeutic role when end-stage renal function and bone disease co-exist remains unclear. This 15-year retrospective cohort study examines the long-term use of BPs in CKD-4 and -5 patients receiving no renal replacement therapy, haemodialysis and renal transplant in a tertiary centre in Sydney, Australia. In multivariate regression adjusting for age, baseline bone mineral density (BMD) and history of fracture, BP use was associated with net gain in lumbar spine bone density in renal transplant recipients over a mean treatment period of 3.5 years (net annual BMD gain of 0.039 g/cm2, p = 0.005). No such benefit was seen in hip BMD in CKD subjects. Regardless of transplant status, CKD patients treated with BPs had no improvement in hip BMD with a general decline in hip BMD across both groups during the study period (hip BMD: transplant recipients decline 0.024 ± 0.81 g/cm2, non-transplant CKD patients decline 0.055 ± 0.84 g/cm2). BP therapy did not result in significant changes in biochemical parameters (ALP, PTH, and phosphate) and no serious adverse effects were detected in association with BP use. In particular, kidney function was not affected by BPs post-transplant (eGFR = 43 ± 29 ml/min/1.73 m2, p = 0.80). BPs preserved lumbar spine bone density in kidney transplant recipients but did not prevent declines in hip bone mineral density in either transplant patients or those with CKD-4 and -5. SummaryThere remains a lack of clarity of the risks vs. benefits of bone-sparing pharmacotherapy in chronic kidney disease Stages 4 and 5. This single-centre 15-year retrospective data analysis showed that bisphosphonates are not associated with any detectable serious adverse effects in CKD-4 and -5 and effective at mitigating lumbar spine bone loss in kidney transplant patients.

The Limited Value of Prior Change in Predicting Future Progression of Juvenile-onset Myopia.

Identifying children at highest risk for rapid myopia progression and/or rapid axial elongation could help prioritize who should receive clinical treatment or be enrolled in randomized clinical trials. Our models suggest that these goals are difficult to accomplish. This study aimed to develop models predicting future refractive error and axial length using children's baseline data and history of myopia progression and axial elongation. Models predicting refractive error and axial length were created using randomly assigned training and test data sets from 916 myopic participants in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study. Subjects were 7 to 14 years of age at study entry with three consecutive annual visits that included cycloplegic A-scan ultrasound and autorefraction. The effect of adding prior change in axial length and refractive error was evaluated for each model. Age, ethnicity, and greater myopia were significant predictors of future refractive error and axial length, whereas prior progression or elongation, near work, time outdoors, and parental myopia were not. The 95% limits for the difference between actual and predicted change were ±0.22 D and ±0.14 mm without prior change data compared with ±0.26 D and ±0.16 mm with prior change data. Sensitivity and specificity for identifying fast progressors were between 60.8 and 63.2%, respectively, when the cut points were close to the sample average. Positive predictive value and sample yield were even lower when the cut points were more extreme. Young, more myopic Asian American children in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study were the most likely to progress rapidly. Clinical trials should expect average progression rates that reflect sample demographics and may have difficulty recruiting generalizable samples that progress faster than that average. Knowing progression or elongation history does not seem to help the clinical decision regarding initiating myopia control.

Effectiveness of rituximab vs. ocrelizumab for the treatment of primary progressive multiple sclerosis: a real-world observational study.

Ocrelizumab, an antiCD-20 antibody, is the only drug approved to treat patients with primary progressive multiple sclerosis (pwPPMS). Not all candidates receive this treatment due to prescription limitations. Rituximab, another antiCD-20 antibody, has been used off-label in pwPPMS before and after ocrelizumab approval. However, studies comparing effectiveness of both drugs are lacking. To evaluate effectiveness of rituximab and ocrelizumab in pwPPMS under real-life conditions. We conducted a multicentric observational study of pwPPMS that started ocrelizumab or rituximab according to clinical practice, with a minimum follow-up of 1year. Data was collected prospectively and retrospectively. Primary outcome was time to confirmed disability progression at 3months (CDW). Secondary outcome was serum neurofilament light chain levels (sNFL) at the end of follow-up. 95 out 111 pwPPMS fulfilled inclusion criteria and follow-up data availability: 49 (51.6%) received rituximab and 46 (48.4%) ocrelizumab. Rituximab-treated patients had significantly higher baseline EDSS, disease duration and history of previous disease-modifying treatment (DMT) than ocrelizumab-treated patients. After a mean follow-up of 18.3months (SD 5.9), 26 patients experienced CDW (21.4%); 15 (30.6%) in the rituximab group; and 11 (23.9%) in the ocrelizumab group. Survival analysis revealed no differences in time to CDW. sNFL were measured in 60 patients and no differences between groups were found. We provide real-world evidence of effectiveness of ocrelizumab and rituximab in pwPPMS. No differences in time to CDW were found between treatments. However, this study cannot establish equivalence of treatments and warrant clinical trial to confirm our findings.

Influence of Baseline Total IgE and History of Previous Omalizumab Use on the Impact of Mepolizumab in Reducing Rate of Severe Asthma Exacerbations: Results From the Real-World REALITI-A Study

Many patients with severe asthma have mixed phenotypes, with eligibility for anti-eosinophilic or anti-immunoglobulin E (IgE) biologics (eg, omalizumab). Here, we assess the impact of baseline total IgE (tIgE) and history of previous omalizumab use on real-world outcomes in patients with severe asthma selected to receive mepolizumab therapy.

Increasing Seizure Activity During Radiation Treatment for High-grade Gliomas - Final Results of a Prospective Interventional Study.

Little is known regarding seizures during radiotherapy for brain tumors. This prospective study investigated seizure activity in patients irradiated for high-grade gliomas. Using a seizure diary, progression of seizure activity was evaluated in 22 patients receiving chemoradiation for grade III (n=1) or IV (n=21) gliomas. Progression was defined as increased frequency of any and/or generalized seizures (>50%) or increased anti-epileptic medication (≥25%). Patients' satisfaction with the diary was assessed using a questionnaire (six scales of 1-7 points). Uni- and multivariable analyses were performed including baseline seizure activity, age, sex, resection, tumor site, performance score, and history of epilepsy/seizures. Ten patients (45%) experienced progression of seizure activity during their radiotherapy course, mainly due to increased seizure frequency (nine patients=41%). Mean values of patients' satisfaction scores ranged between 3.92 and 4.92 points. Radiotherapy of high-grade gliomas can increase seizure activity. Patients require close monitoring to initiate or adjust anti-epileptic medication.

Effect of ACEi and ARBs vs Non ACEi/ ARBs in Hypertension with Respect to Renal Outcomes in COVID-19 Infection: A Retrospective Cohort Study

Introduction: The Acute Kidney Injury (AKI) is one of the most common complications following Coronavirus Disease2019 (COVID-19) infection. The presence of high density of Angiotensin Converting Enzyme 2 (ACE2) receptors in Type 2 alveolar epithelial cells, vascular endothelium and proximal convoluted tubules explains the involvement of systemic organs in COVID-19 infection. Systemic hypertension is one of the most common co-morbidities associated with COVID19 infection with high mortality, specially in patients of severe disease with AKI. The antihypertensives, which work by Renin Angiotensin Aldosterone System (RAAS) inhibition like ACE inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs) can upregulate the enzyme ACE2, so the incidence and risk of AKI in hypertensive patients who have COVID-19 infection is common. Aim: To determine the risk of developing AKI and mortality in hypertensive patients, with COVID-19 infection, on ACEi or ARBs as compared to non ACEi and non ARBs. Materials and Methods: This was a retrospective cohort study conducted on 116 admitted hypertensive patients, who were positive for COVID-19 infection from the month of April 2021 to September 2021. The study patients were divided into two groups- group A and group B. The group A was on ACEi or ARBs and group B was on non ACEi/ARBs. The patients baseline history, clinical examination and the blood investigations like Renal Function Test (RFT), Liver Function Test (LFT), Echocardiography (ECG), Chest X-ray, 2 Dimensional ECHO (2D-ECHO), Arterial Blood Gases (ABG) were done for all the patients. The normal Blood Pressure (BP) was less than 140/90 mmHg.The normal creatinine was 0.6 to 1.5 mg/dL and normal urea was 19 to 45 mg/dL. The RFT was repeated on every day of hospital stay duration. The patients were followed-up for one month from day of starting the study. The parameters were recorded, assessed on day 7th and day 30th of the study. All parameters were compared between the final outcome of the patients by 30th day of study and the class of antihypertensives used to control hypertension. The Pearson’s Chi-square test, Fisher’s exact and Analysis of Variance (ANOVA) were used for testing the significance of relationship and outcome between group A and group B study patients. Results: The mean duration of hypertension in both the groups was 7.6 years. In group A 53 (45.7%) were on ACEi and ARBs, in group B, 63 (54.3%) were on non ACEi/ARBs. In the group A, the serum creatinine of more than &gt;1.5 mg/dL at 7th day of study was found in 28 (52.8%) patients and on 30th day it was found in 8 (15.09%) patients (p-value=0.065). Again in the group A, blood urea of more than 45 mg/dL on 7th day of study was found in 30 (56.6%) patients and on 30th day it was found in 9 (16.98%) patients (p-value=0.064). In the group B, the serum creatinine &gt;1.5 mg/dL on day 7th of study was found in 36 (57.14%) patients and on day 30th it was in 24 (38.09%) patients (p-value=0.061). Again in group B, the blood urea of &gt;45 mg/dL on day 7th was found in 35 (55.55%) patients and on day 30th it was found in 16 (25.39%) patients (p-value=0.074). Of the patients on group A (ACEi and ARBs) 28 (52.83%) were on supplemental oxygen, 12 (22.6%) were on Non Invasive Ventilation (NIV), one was intubated and 12 (22.6%) did not require oxygen (p-value=0.727). Of the patients on group B (non ACEi/ARBs) 33 (52.4%) were on supplemental oxygen, 12 (19.04%) were on NIV, 5 (7.93%) were intubated and 13 (20.63%) did not require oxygen. In the patients of group A, 35 (66.03%) were recovered and 18 (33.96%) died, in the group B 40 (63.49%) cases were recovered, while 23 (36.50%) died (p-value=0.781). Conclusion: There was no significant and demonstrable association between specific groups of antihypertensives with renal outcomes and mortality in hypertensive patients with COVID-19 infection. By above observations this study concludes that, there is no specific role of ACE2 receptors in renal outcome and mortality in hypertension with COVID-19 infection.

Outcomes of patients with end-stage kidney disease hospitalized with COVID-19: A single-center experience from Eastern India

Aim: This study aimed to describe the clinical characteristics, survival outcome, and its correlation with biochemical parameters in coronavirus disease-2019 (COVID-19)-infected patients with end-stage kidney disease (ESKD). Materials and Methods: A prospective observational study was on hospitalized patients with confirmed COVID-19 infection from September 1, 2020 to October 31, 2020. Data related to demographics, baseline history of comorbid conditions, dialysis-specific data, details on hospital admissions, COVID-19 treatment regimen, laboratory investigations, computed tomography (CT) severity score, COVID-19 Reporting and Data System score, and clinical outcomes (improved/death), duration of hospital stay, oxygen/vasopressor support were collected. Results: A total of 216 ESKD patients with COVID-19 infection were included in this study. The median age was 48.0 years (74.5% men, 25.5% women). Severe acute respiratory infection (44.7%), hypertension (28.2%), and type 2 diabetes mellitus (22.4%) were the most common comorbidities. Elevated levels of serum creatinine (9.3 mg/dL) and blood urea nitrogen (84.8 mg/dL) were observed in the patients with COVID-19 infection. The change in mean levels of serum creatinine and estimated glomerular filtration rate from baseline to post-treatment was significant (0.9 [95% CI: 0.7, 1.1; P < 0.001] and 3.4 [95% CI: 3.2, 3.6; P < 0.001], respectively). Approximately, 79.6% (n = 172) of patients improved post-treatment. Serum creatinine (1.786, 95% CI: 1.031, 3.095; 0.039) and ferritin levels (51.959, 95% CI: 7.901, 341.685; P < 0.001) remained significantly and independently associated with survival. The median time to clinical survival was 17.0 days. Conclusion: Serum creatinine and ferritin levels were independently associated with survival.

Association of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists use with risk of atrial fibrillation after pacemaker implantation among very old patients

It remains unknown whether and to what extend the angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can play a role in the development of atrial fibrillation (AF) after pacemaker implantation in very old patients. Therefore, we aimed to investigate the association between oral ACEIs or ARBs and the risk of developing AF in very old patients after pacemaker implantation. Patients above 80 years old with pacemaker implantation and without baseline history of AF were included and their real-world information about ACEIs or ARBs use was extracted from electronic medical records. New AF cases were confirmed via the records of outpatient visits. The multivariable Cox proportional-hazards model was used to evaluate the associations between oral ACEIs or ARBs and risk of AF after pacemaker implantation. Among a total of 388 identified patients aged 80 to 98 years, 118 used ACEIs, 174 had ARBs therapy, and 115 AF were identified after pacemaker implantation during a median follow-up time of 3.1 years. After adjustment for potential confounders, patients with daily use of ARBs had a relatively lower risk of AF after pacemaker implantation (HR: 0.627, 95% CI: 0.425, 0.926; P = 0.019) compared with those non-users, whereas ACEIs therapy didn't show a significant relation with AF risk (HR: 1.335, 95% CI: 0.894, 1.995; P = 0.157). In conclusion, for very old patients with a permanent pacemaker, daily use of oral ARBs was associated with a relative lower risk of AF after pacemaker implantation, however, daily use of ACEIs was not related with AF risk.

Using supervised machine learning approach to predict treatment outcomes of vedolizumab in ulcerative colitis patients

ABSTRACT With recent advances in machine learning, we demonstrated the use of supervised machine learning to optimize the prediction of treatment outcomes of vedolizumab through iterative optimization using VARSITY and VISIBLE 1 data in patients with moderate-to-severe ulcerative colitis. The analysis was carried out using elastic net regularized regression following a 2-stage training process. The model performance was assessed through AUROC, specificity, sensitivity, and accuracy. The generalizable predictive patterns suggest that easily obtained baseline and medical history variables may be able to predict therapeutic response to vedolizumab with clinically meaningful accuracy, implying a potential for individualized prescription of vedolizumab.

Bariatric Surgery Leads to a Reduction in Antibodies to Apolipoprotein A-1: a Prospective Cohort Study

PurposeAutoantibodies against apolipoprotein A-1 have been associated with cardiovascular disease, poorer CV outcomes and all-cause mortality in obese individuals. The impact of bariatric surgery (BS) on the presence of circulating anti-apoA-1 IgG antibodies is unknown. This study aimed to determine the effect of bariatric surgery on auto-antibodies titres against Apolipoprotein A-1 (anti-apoA-1 IgG), looking for changes associated with lipid parameters, insulin resistance, inflammatory profile and percentage of excess body mass index loss (%EBMIL).Materials and MethodsWe assessed 55 patients (40 women) before, 6 and 12 months post-operatively. Baseline and post-operative clinical history and measurements of body mass index (BMI), serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), apoA-1, highly sensitive C-reactive protein (hsCRP), fasting glucose (FG), glycated haemoglobin (HbA1c) and HOMA-IR were taken at each point. Human anti-apoA-1 IgG were measured by ELISA.ResultsThe mean age of participants was 50 years. BS significantly improved BMI, %EBMIL triglycerides, HDL-C, apoA-1, hsCRP, HBA1c, FG and HOMA-IR. Baseline anti-apoA-1 IgG seropositivity was 25% and was associated with lower apoA-1 and higher hsCRP levels. One year after BS, anti-apoA-1 IgG seropositivity decreased to 15% (p = 0.007) and median anti-apoA-1 IgG values decreased from 0.70 (0.56–0.84) to 0.47 (0.37–0.61) AU (p < 0.001). Post-operative anti-apoA-1 IgG levels were significantly associated with a decreased post-surgical %EBMIL at 1 year.ConclusionBariatric surgery results in significant reduction in anti-apoA-1 IgG levels, which may adversely influence weight loss. The exact mechanisms underpinning these results are elusive and require further study before defining any clinical recommendations.Graphical abstract

Women With Osteoarthritis Are at Increased Risk of Ischemic Stroke: A Population-Based Cohort Study.

BackgroundOsteoarthritis (OA) is more prevalent in women with age. Comorbidities are prevalent in OA patients. In this study, we conducted a follow-up study to evaluate whether women with OA are at an increased risk of ischemic stroke using insurance claims data of Taiwan.MethodsWe identified 13,520 women with OA aged 20–99 newly diagnosed in 2000–2006 and 27,033 women without OA for comparison, frequency matched by age and diagnosis date. Women with baseline history of hypertension and other disorders associated with stroke were excluded for this study. Incident ischemic stroke was assessed by the end of 2013. A nested case-control analysis was used to identify factors associated with the stroke in the OA cohort.ResultsThe incidence rate of ischemic stroke in the OA cohort was 1.5-fold greater than that in comparisons (1.93 versus 1.26 per 1,000 person-years), with an adjusted hazard ratio of 1.34 (95% confidence interval [CI], 1.09–1.66). The nested case-control analysis showed that stroke cases were twice as likely to develop hypertension during the follow-up period than controls without stroke. The ischemic stroke risk was significantly associated with hypertension (odds ratio [OR] 1.84; 95% CI, 1.37–2.46) and atrial fibrillation (OR 2.25; 95% CI, 1.24–4.09). Ischemic stroke was not associated with the use of non-steroidal anti-inflammatory drugs or aspirin.ConclusionWomen with OA are at an elevated risk of ischemic stroke. A close monitoring of hypertension, atrial fibrillation, and other stroke related comorbidities is required for stroke prevention for OA patients.

Association Between the ACE Insertion/Deletion Polymorphism and Risk of Lower-Limb Amputation in Patients With Long-Standing Type 1 Diabetes.

The ACE insertion/deletion (I/D) polymorphism has been widely studied in people with diabetes, albeit not with regard to lower-limb amputation (LLA). We examined associations among this polymorphism, plasma ACE concentration, and LLA in people with type 1 diabetes. ACE I/D genotype and plasma ACE were assessed in three prospective cohorts of participants with type 1 diabetes. LLA was defined as minor (below-the-ankle amputation consisting of at least one ray metatarsal resection) or major (transtibial or transfemoral) amputation. Linear, logistic, and Cox regression models were computed to evaluate the likelihood of prevalent and incident LLA by ACE genotype (XD [ID or ID] vs. II) and plasma ACE, after adjusting for confounders. Among 1,301 participants (male 54%, age 41 ± 13 years), 90 (6.9%) had a baseline history of LLA. Baseline LLA was more prevalent in XD (7.4%) than in II genotype (4.5%, odds ratio [OR] 2.17 [95 %CI 1.03-4.60]). Incident LLA occurred in 53 individuals during the 14-year follow-up and was higher in XD versus II carriers (hazard ratio 3.26 [95% CI 1.16-13.67]). This association was driven by excess risk of minor, but not major, LLA. The D allele was associated with increased prevalent LLA at the end of follow-up (OR 2.48 [1.33-4.65]). LLA was associated with higher mean (95% CI) ACE levels in II (449 [360, 539] vs. 354 [286, 423] ng/mL), but not XD (512 [454, 570] vs. 537 [488, 586]), carriers. This report is the first of an independent association between ACE D allele and excess LLA risk, mainly minor amputations, in patients with type 1 diabetes.