Clinical Acute Kidney Injury and Histologic Acute Tubular-Interstitial Injury and Their Prognosis in Diabetic Nephropathy

<b><i>Introduction:</i></b> Histologic acute tubular-interstitial injury (hATI) is often observed in patients with diabetic nephropathy (DN). This study aimed to determine the relationship between hATI and clinical acute kidney injury (cAKI) and evaluate significance of hATI in patients with DN. <b><i>Methods:</i></b> Patients with biopsy-proven DN through 2003–2018 in our center were selected. The prevalence of hATI and its correlations with cAKI, tubular injury biomarkers, and serum creatinine were investigated. The renal survival rates and prognostic factors were analyzed by Kaplan-Meier curve and Cox regression model, respectively. <b><i>Results:</i></b> Of 1,414 patients with DN, 70.4% were male, with a median age of 50.0 years. The incidences of cAKI and hATI were 8.6% and 57.8%, respectively. The severities of most hATI were mild (91.0%). The incidence of cAKI in those with hATI was only 12.2%. The incidences of cAKI positively correlated with the scores of hATI (Kendall <i>r</i> = 0.273, <i>p</i> &#x3c; 0.001). The presence of hATI was related to rapid creatinine rise and increased tubular injury biomarkers although without cAKI. After adjusting for significant covariates, multivariate Cox models showed that patients with hATI alone were one and a half times more likely to develop ESRD (hazard ratio [HR]: 1.46; 95% CI, 1.05–2.02) than those without hATI or cAKI, and patients with hATI plus cAKI were 3 times more likely to develop ESRD (HR: 2.96; 95% CI, 1.85–4.72). <b><i>Conclusion:</i></b> Our findings indicated that hATI was common in patients with DN where the majorities were mild hATI and without cAKI. hATI was an independent risk factor of DN progression, regardless of episodes of cAKI.

Perceptions of Social Support Sufficiency Among Older Adults With HIV in Sub-Saharan Africa

Globally, the greatest number of older people with HIV (OPWH) are in sub-Saharan Africa (3.7 million). This population will continue to expand with greater access to anti-retroviral therapy. Compared to OPWH in high income counties, these OPWH have constrained access to government and community-based services and largely rely on assistance from family, friends, and neighbors for their social support needs. We examined factors related to perceptions of instrumental and emotional support sufficiency (availability and adequacy) among OPWH age 50 and older in Uganda (n = 101) and South Africa (n = 108). Significant covariates of instrumental support sufficiency included not having an AIDS diagnosis, greater support from family, and less support from friends. Significant covariates of emotional support sufficiency were fewer depressive symptoms, greater support from family, and geographic location (Uganda). Explanation of these findings based on social network characteristics and implications for policy and program development will be discussed.

Effects of Chengqi Decoction on Complications and Prognosis of Patients with Pneumonia-Derived Sepsis: Retrospective Cohort Study

Purpose. A specific and efficacious method for treatment of pneumonia-derived sepsis is lacking. Chengqi decoction has been used for treatment of pneumonia-derived sepsis, but a clinical trial on patients with pneumonia-derived sepsis is lacking, a gap in the literature that we sought to fill. Patients and Methods. 282 patients with pneumonia-derived sepsis admitted to the intensive care unit of our hospital were selected. They were divided into the treatment group (141 cases) and control group (141 cases). Both groups underwent conventional treatment, but Chengqi decoction (in the form of enema) was given to the treatment group. Mortality, morbidity (abdominal distension and gastrointestinal bleeding), duration of antibiotic use, and use of vasoactive agents were documented 28 days after the drug was used. Results. The treatment group reduced mortality and morbidity (abdominal distension) ( P < 0.05 ). After adjustment for significant covariates, 28-day survival was similar for the whole group (hazard ratio (HR): 0.48; 95% confidence interval (CI): 0.23–0.97; P = 0.037 ), for the subgroup (n = 120) with Acute Physiology and Chronic Health Evaluation II score ≥25 (HR: 0.180; 95% CI: 0.032–0.332; P = 0.039 ) and for the subgroup (n = 66) with N-terminal B-type natriuretic peptide <1800 (0.059, 0.004–0.979, and 0.019). There was no difference between the two groups for the duration of antibiotic use, major bleeding, or use of vasoactive drugs. Conclusions. Chengqi decoction improved 28-day survival and reduced the prevalence of abdominal distension in patients with pneumonia-derived sepsis.

Crypto Exchanges and Credit Risk: Modeling and Forecasting the Probability of Closure

While there is increasing interest in crypto assets, the credit risk of these exchanges is still relatively unexplored. To fill this gap, we considered a unique dataset of 144 exchanges, active from the first quarter of 2018 to the first quarter of 2021. We analyzed the determinants surrounding the decision to close an exchange using credit scoring and machine learning techniques. Cybersecurity grades, having a public developer team, the age of the exchange, and the number of available traded cryptocurrencies are the main significant covariates across different model specifications. Both in-sample and out-of-sample analyzes confirm these findings. These results are robust in regard to the inclusion of additional variables, considering the country of registration of these exchanges and whether they are centralized or decentralized.

Comorbidity Between Internalising and Externalising Disorders Among Adolescents: Symptom Connectivity Features and Psychosocial Outcome

Internalising disorders are highly prevalent conditions in adolescence and tend to co-occur with externalising disorders. The present study used a symptom network approach to examine the interplay between symptoms of internalising disorders among adolescents with comorbid internalising and externalising disorders. Data comes from the National Comorbidity Survey—Adolescent Supplement, a nationally representative survey of adolescents aged 13 to 18 years. The most central symptoms across the disorders in the network were poor self-esteem and worry. The comorbidity between anxiety and depression increases the probability of having comorbid externalising disorders. Adolescents with both internalising and externalising disorders had the highest rate of health service utilisation. Comorbidity group, lifestyle factors, deficits in cognitive and academic competence and coping skills were significant covariates of the mental health outcomes. Understanding comorbidity profile of internalising and externalising disorders and central symptoms that bridge these disorders could have important clinical implications.

Covariate effects and population pharmacokinetic analysis of the anti-FGFR2b antibody bemarituzumab in patients from phase 1 to phase 2 trials

Purpose A population pharmacokinetic (PK) analysis of the anti-fibroblast growth factor receptor 2b antibody, bemarituzumab, was performed to evaluate the impact of covariates on the PK and assess whether dose adjustment is necessary for a future phase 3 trial. Methods Serum concentration data were obtained from three clinical trials, with 1552 bemarituzumab serum samples from 173 patients, and were analyzed using nonlinear mixed-effects modeling. Results A two-compartment model with parallel linear and nonlinear (Michaelis–Menten) elimination from the central compartment best described the bemarituzumab serum concentration data. The final model estimated a typical linear clearance (CL) of 0.311 L/day, volume of distribution in the central compartment (Vc) of 3.58 L, distribution clearance (Q) of 0.952 L/day, volume of distribution in the peripheral compartment (Vp) of 2.71 L, maximum drug elimination by nonlinear clearance (Vmax) of 2.80 μg/day, and Michaelis–Menten constant (Km) of 4.45 μg/mL. Baseline body weight, baseline albumin, gender, and chemotherapy were identified as statistically significant covariates on the PK of bemarituzumab. Given the low interindividual variability of bemarituzumab key PK parameters (CL and Vc) and the small or modest effect of all statistically significant covariates on bemarituzumab exposure at steady-state, no covariate is expected to have clinically meaningful effects on bemarituzumab exposure. Conclusion No covariate had a clinically meaningful impact on bemarituzumab exposure. These results indicate that dose adjustment of bemarituzumab is not necessary, based on the aforementioned covariates, for a future phase 3 trial in gastric and gastroesophageal junction adenocarcinoma population with FGFR2b overexpression in combination with mFOLFOX6.

A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation

Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population. Methods: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit’s binding sites over time. Results: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO (p = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2–4.7) mg/L under ECMO and 2.5 (1.4–3.9) mg/L without ECMO (p = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure. Conclusions: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.

Does timing of chemotherapy impact breast satisfaction after breast conservation therapy and mastectomy with immediate reconstruction?

589 Background: Receipt of chemotherapy is associated with decreased postoperative breast satisfaction, but whether timing as neoadjuvant (NAC) versus adjuvant (AC) affects this outcome after breast conservation therapy (BCT) and mastectomy with immediate reconstruction (M-IR) is unclear. Methods: We retrospectively identified patients treated with chemotherapy and breast surgery (BCT and M-IR), from 1/2017-12/2019, who completed ≥ 1 BREAST-Q survey through 12/2020. Mean (standard deviation [SD]) Q-scores for satisfaction with breasts (SATBR) were compared between NAC versus AC groups in BCT and M-IR cohorts, respectively. Higher Q-scores on a 0-100 scale indicate superior satisfaction. A minimum 4-point difference was considered clinically important. Chemotherapy timing and significant covariates on univariate analyses were entered in multivariable linear regressions of 1- and 2-year SABTR. Results: 640 patients had BCT and 602 had M-IR; 210 (33%) BCT patients and 294 (49%) M-IR patients had NAC. Compared with M-IR, SATBR was higher after BCT in both NAC and AC groups, at all postoperative timepoints (Table). Following BCT, SABTR was highest in both NAC and AC groups at 6 months and returned to baseline in the NAC group by year 3. In the M-IR cohort, 331 (55%) patients had radiation and 120 (20%) had complications requiring re-operation or hospitalization. Compared with baseline, mean (SD) Q-scores were substantially lower at 6 months but improved to near baseline at 3 years in both NAC and AC groups. On multivariable analysis, radiation was associated with decreased SABTR at 1 year (Beta, -11; 95% CI, -17, -5.0; p<0.001) and 2 years (Beta, -12; 95% CI, -19, -5.5; p<0.001), as were complications at 1 year (Beta, -6.1; 95% CI, -12, -0.34; p=0.038) but not 2 years (Beta, -5.5; 95% CI, -12, 0.92; p=0.09). After multivariable adjustment, NAC was not significantly associated with 1- or 2-year SABTR after M-IR or BCT. Conclusions: SABTR was higher in BCT compared with M-IR cohorts, independent of chemotherapy timing. Following BCT, SABTR was lower in the NAC group at years 2-3 but remained at baseline or higher at all timepoints. In the M-IR cohort, both groups endorsed lower than baseline SABTR in years 0-2 but returned to near baseline at 3 years. Radiation and complications were independent predictors of decreased SABTR, but our findings suggest that patients who experience complications after M-IR can expect return to baseline breast satisfaction by 2 years.[Table: see text]

086 Sleep midpoint after job loss predicts breakfast skipping patterns

Introduction Few studies have examined circadian phase after job loss, an event that upends daily routine. It is common that a daily routine begins with the consumption of breakfast, and breakfast behavior may contribute to health status in adults. Therefore, we sought to examine whether a later midpoint of sleep was associated with breakfast skipping among adults whose schedules were no longer dictated by employment. Methods Data were obtained from the Assessing Daily Activity Patterns Through Occupational Transitions (ADAPT) study. The sample of 155 participants had involuntarily lost their jobs in the last 90 days. Both cross-sectional and 18-month longitudinal analyses assessed the relationship between sleep midpoint after job loss and current and later breakfast skipping. Assessment periods were 14 days. Sleep was measured via actigraphy, and breakfast skipping was measured via daily diary (1 = had breakfast; 0 = did not have breakfast). The midpoint of sleep was calculated as the circular center based on actigraphy sleep onset and offset times. Results The midpoint of sleep at baseline was negatively associated with breakfast consumption at baseline (B = -.09, SE = .02, p = .000). Also, a later midpoint was associated with breakfast skipping over the next 18 months (estimate = -.08; SE = .02; p = .000). Prospective findings remained significant when adjusting for gender, ethnicity, age, perceived stress, body mass index (BMI), education, and reemployment over time. Education (estimate = 14.26, SE = 6.23, p &lt; .05) and BMI (estimate = -.51, SE = .25, p &lt; .05) were the only significant covariates. No other sleep indices predicted breakfast behavior cross-sectionally or prospectively. Conclusion Consistent with research in adolescents, unemployed adults with a later circadian phase are more likely to skip breakfast more often. Breakfast skipping was also associated with higher BMI. Taken together, these findings provide support for the future testing of sleep/wake scheduling interventions to modify breakfast skipping and potentially mitigate weight gain after job loss. Support (if any) #1R01HL117995-01A1

In-Hospital Glycemic Dysregulation Associated With Worse Outcomes in COVID-19

Introduction: Evidence establishes that COVID-19 patients with DM2 are at increased risk for severe disease and worse outcomes. Peer reviewed data is sparse comparing glycemic control and clinical outcomes among COVID-19 patients with vs. without DM2, and thus we sought to address this gap. Methods: We selected patients at least 18 years old who expired or were discharged between March 16, 2020 through September 15, 2020. Principal analysis compared glycemic patterns among patients with DM2 vs. non-DM2. Median, coefficient of variation (CV), maximum and minimum glucose parameters were computed to characterize longitudinal glycemic patterns. Logistic regression modeling identified significant (p&lt;.05) associations between composite outcome vs. glycemic parameters and putative risks for progression to severe COVID-19. Receiver operating characteristic (ROC) curve identified cut points for glycemic parameters. Cox regression models were employed to control for significant confounders. Continuous data summarized as median was compared using Kruskal-Wallis test. Discrete data were compared with Pearson’s chi-square test. Two-tailed p&lt;.05 was significant. Results: Among 494 patients, 157 (32%) had DM2 with no intergroup differences in age (68 [56–79]), sex (52% male, 48% female), or race (68% Caucasian, 19% Other, 13% African American). Insulin was administered to DM2 (93%) and non-DM2 (54%) patients (p&lt;.0001). Comorbidities were more prevalent in DM2, including cardiovascular (68% vs. 54%, p=.003), renal (72% vs. 52%, p&lt;.0001) and obesity (51% vs. 38%, p&lt;.0001). Markers including D-dimer (0.98 [0.61–1.95] mg/L), lactate dehydrogenase (308 [230–392] U/L), ferritin (436 [174–856] ng/mL), and triglycerides (172 [109–239] mg/dL), were not different in DM2 vs. non-DM2 (p&gt;.05). CRP was greater in patients with (8.6 [3.6–14.6]) vs. without (6.1 [2.0–12.6]) DM2 (p=.005). Baseline glucose in DM2 (163 [121–253] mg/dL) vs. non-DM2 (107 [96–124] mg/dL) was significantly greater, with former an independent predictor of composite outcome (p=.0005). Cox modeling of other glucose parameters in DM2 vs. non-DM2 demonstrated various impact regarding risk for composite outcome including median (155 [128–209], p=.46) vs. (103 [94–118], p=.09); coefficient of variation (28 [19–38], p=.08) vs. (15 [9–20], p=.002); maximum (252 [187–362], p=.0005) vs. (129 [110–156], p=.002); and minimum (99 [79–128], p=.95) vs. (89 [81–98], p=.02). The unified baseline glucose cut point for composite outcome risk controlled for significant covariates was 138 gm/dL (p&lt;.0001), which included respectively 20% and 10% of patients with and without DM2. Conclusion: Glycemic dysregulation in COVID-19 patients is independently associated with ICU admission and/or hospital mortality. Presence of DM2 amplifies glycemic dysregulation, but risk stratification appears warranted in all COVID-19 patients.