Lower Nadir Research Articles

Rituximab Associated Hypogammaglobulinemia in Autoimmune Disease.

ObjectiveTo evaluate the characteristics of patients with autoimmune disease with hypogammaglobulinemia following rituximab (RTX) and describe their long-term outcomes, including those who commenced immunoglobulin replacement therapy.MethodsPatients received RTX for autoimmune disease between 2003 and 2012 with immunoglobulin G (IgG) <7g/L were included in this retrospective series. Hypogammaglobulinemia was classified by nadir IgG subgroups of 5 to <7g/L (mild), 3 to <5g/L (moderate) and <3g/L (severe). Characteristics of patients were compared across subgroups and examined for factors associated with greater likelihood of long term hypogammaglobulinemia or immunoglobulin replacement.Results142 patients were included; 101 (71%) had anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis (AAV), 18 (13%) systemic lupus erythematosus (SLE) and 23 (16%) other conditions. Mean follow-up was 97.2 months from first RTX. Hypogammaglobulinemia continued to be identified during long-term follow-up. Median time to IgG <5g/L was 22.5 months. Greater likelihood of moderate hypogammaglobulinemia (IgG <5g/L) and/or use of immunoglobulin replacement therapy at 60 months was observed in patients with prior cyclophosphamide exposure (odds ratio (OR) 3.60 [95% confidence interval (CI) 1.03 – 12.53], glucocorticoid use at 12 months [OR 7.48 (95% CI 1.28 – 43.55], lower nadir IgG within 12 months of RTX commencement [OR 0.68 (95% CI 0.51 – 0.90)] and female sex [OR 8.57 (95% CI 2.07 – 35.43)]. Immunoglobulin replacement was commenced in 29/142 (20%) and associated with reduction in infection rates, but not severe infection rates.ConclusionHypogammaglobulinemia continues to occur in long-term follow-up post-RTX. In patients with recurrent infections, immunoglobulin replacement reduced rates of non-severe infections.

417 Transgender Hormone Therapy and Sleep-Disordered Breathing

Abstract Introduction Sex hormones may affect human respiration during wakefulness and sleep. Testosterone has been associated with increased obstructive respiratory events contributing to sleep-disordered breathing (SDB) in men, whereas a protective effect against SDB has been attributed to estrogen in women. These associations, primarily observed in cisgender populations, have been rarely examined in transgender individuals on hormone replacement therapy (HRT). The present study investigated associations between HRT and SDB in transgender adults. Methods A chart review of medical records from transgender patients was conducted in a large academic sleep medicine center. Individuals were included if they were at least 18 years old, had one or more sleep complaints, and SDB testing results available. Participants were then stratified by affirmed gender (transmasculine and transfeminine) and by HRT status. We used descriptive statistics procedures to examine differences between gender and HRT groups. Associations between HRT and the apnea-hypopnea index (AHI) were estimated with age-adjusted linear regression models. Results Of the 194 individuals identified, 89 satisfied the inclusion criteria. Nearly half of participants were transmasculine (52%). The mean age was 38±13 years, and mean body mass index was 34.7±9.0 Kg/m2. Approximately 60% of participants were on HRT at the time of SDB evaluation. Transmasculine people who were prescribed testosterone had a significantly increased AHI and lower oxygen nadir in comparison to transmasculine individuals not on testosterone (AHI 36.8±37.8/hour vs.15.3±16.6/hour, p=0.01; oxygen nadir 83.4±8.3% vs. 89.1±2.4%, p=0.001). In contrast, differences between transfeminine people with and without feminizing HRT (androgen blocker + estrogen) were not statistically significant (AHI 21.4±27.7/hour vs. 27.7±26.0/hour, p=0.45; oxygen nadir 86.5±6.7% vs. 84.1±7.7%, p=0.29). Linear regression models adjusted for age found an association between HRT and AHI for transmasculine (β=16.7, 95% CI 2.7, 30.8), but not for transfeminine participants (β=-2.5, 95% CI -17.9, 12.9). Conclusion These findings suggest differential associations between HRT and AHI among transgender individuals, with transmasculine on testosterone having a significant increase in AHI. Prospective studies with large sample sizes are warranted to evaluate these associations. Support (if any) Dr. Gavidia’s work was supported by an NIH/NINDS T32-NS007222 grant

Early Moderate Fluid Restriction and the Risk of Delayed Hyponatremia Following Transsphenoidal Surgery

Background: The most common cause for readmission after transsphenoidal surgery (TSS) is hyponatremia (hypoNa). Delayed hypoNa, defined as hypoNa occurring 3 to 14 days post TSS, occurs in up to 35% of patients and, if severe, can be life-threatening. We conducted a preliminary prospective study comparing two approaches of postoperative fluid management and hypothesized that patients treated with early postoperative fluid restriction would have decreased rates of delayed hypoNa.Methods: Patients scheduled for TSS were randomly assigned to the control (CON, n=65) or fluid restriction group (Total FR (EXP 1 + EXP 2), n=57). Patients with chronic kidney disease stage III or greater, diabetes insipidus, chronic hyponatremia, or untreated adrenal insufficiency or hypothyroidism were excluded. All patients were started on postoperative weight-based intravenous fluids until postoperative day (POD) 1 and allowed to drink freely. Patients in the EXP 1 group (n=39) were fluid restricted to 1.8 liters/day (2 liters/day if weight > 100 kg) from POD 3 through POD 14. The fluid restriction was changed to 1 liter/day (1.2 liters/day if weight > 100 kg) (EXP 2, n=18) during the study due to interim analysis suggesting a trend toward a reduction in the incidence of hypoNa with fluid restriction. Patients in the CON group were instructed to drink ad lib. Serum sodium (Na) levels were checked every 8 hours in the hospital and on POD 3, 7, 10, and 14. Average and nadir Na between POD 3 and POD 14, incidence of mild (130-134 mEq/L), moderate (125-129 mEq/L), and severe (< 125 mEq/L) hypoNa, and readmission for hypoNa were evaluated. Mann-Whitney U test, Fischer’s exact test, Pearson’s chi-square, and T-test were used for statistical analysis.Results: Nadir Na was lower in CON compared to EXP 2 (135.1 ± 5.8 vs 138.4 ± 2.8, p=0.024). There was a trend toward a decreased incidence of hypoNa in EXP 2 (11%) compared to CON (30%) (p=0.133). Although there was no significant difference in the incidence of hypoNa (p=0.323) between CON and the EXP 1 and EXP 2 groups combined (Total FR), there was a trend toward a lower nadir Na (135.1 ±5.8 vs 137 ± 4.6, p=0.082) and average Na (138.8 ± 3.1 vs139.8 ± 2.5, p=0.140) in CON versus Total FR group, respectively. There was no statistically significant difference in average Na or incidence of hypoNa in CON compared to EXP 1. The incidence of mild, moderate, and severe hyponatremia was similar among groups, except in EXP 2 which had a lower, although not statistically significant, incidence of severe hyponatremia (0% vs 7.7%) and readmission for hyponatremia (5.6% vs 17.5%) compared to CON. There was no difference in the incidence of acute kidney injury or hypernatremia between groups.Conclusion: Preliminary results suggest early moderate fluid restriction after TSS may reduce the incidence of delayed hyponatremia as compared to mild or no fluid restriction. Further analysis with more participants is needed.

Progression Risk in People with HIV and COVID-19: Predictive Performance of Current Risk Scores.

People with HIV (PWH) might have a higher risk of adverse coronavirus disease 2019 (COVID-19) outcomes. Several scores were developed to predict COVID-19 progression to critical disease and are often used among PWH. We assessed the performance of two commonly used risk equations among PWH and COVID-19. Participants were identified from a multicenter cohort of 6,361 PWH on regular follow-up at 2 university hospitals. Of 99 HIV-infected individuals with confirmed SARS-CoV-2 infection, 63 had complete data and were included in this analysis. CALL and COVID-GRAM scores were calculated and participants were stratified into low-, intermediate-, and high-risk groups for each. Discrimination was assessed using receiver operating characteristic curves. Calibration was evaluated using observed versus expected (O:E) ratios and the Hosmer-Lemeshow χ2 goodness-of-fit statistic. Scores were adjusted by increasing one category level in individuals with nadir CD4 lymphocyte count <200/μL. Participants had a median nadir and current CD4 counts of 207 [interquartile range (IQR) 119-345] and 440 (IQR 280-719) cells/μL. Ten (15.9%) individuals progressed to critical disease and 4 (6.3%) died. Assessed scores showed acceptable discrimination (area under the curve 0.701-0.771) and were overall calibrated (O:E ratio 1.01). However, both overestimated the risk of progression among individuals in the low- and high-risk categories, whereas they underestimated the risk in the intermediate category (O:E 1.20-1.21). Thus, 50% of critically ill individuals were not identified as high risk. Assigning PWH with low nadir CD4 counts a higher risk of progression reduced the proportion of individuals not identified to 20%. COVID-19 risk scores had lower performance in PWH compared with that described in the general population and failed to adequately identify individuals who progressed to critical disease. Adjustment for nadir CD4 partially improved their accuracy. Risk equations incorporating HIV-related factors are needed.

Incidence and risk factors for secondary pulmonary infections in patients hospitalized with coronavirus disease 2019 pneumonia

BackgroundSecondary pulmonary infections (SPI) have not been well described in COVID-19 patients. Our study aims to examine the incidence and risk factors of SPI in hospitalized COVID-19 patients with pneumonia. MethodsThis was a retrospective, single-center study of adult COVID-19 patients with radiographic evidence of pneumonia admitted to a regional tertiary care hospital. SPI was defined as microorganisms identified on the respiratory tract with or without concurrent positive blood culture results for the same microorganism obtained at least 48 h after admission. ResultsThirteen out of 244 (5%) had developed SPI during hospitalization. The median of the nadir lymphocyte count during hospitalization was significantly lower in patients with SPI as compared to those without SPI [0.4 K/uL (IQR 0.3–0.5) versus 0.6 K/uL (IQR 0.3–0.9)]. Patients with lower nadir lymphocyte had an increased risk of developing SPI with odds ratio (OR) of 1.21 (95% CI: 1.00 to 1.47, p = 0.04) per 0.1 K/uL decrement in nadir lymphocyte. The baseline median inflammatory markers of CRP [166.4 mg/L vs. 100.0 mg/L, p = 0.01] and d-dimer (18.5 mg/L vs. 1.4 mg/L, p<0.01), and peak procalcitonin (1.4 ng/mL vs. 0.3 ng/mL, p<0.01) and CRP (273.5 mg/L vs. 153.7 mg/L, p<0.01) during hospitalization were significantly higher in SPI group. ConclusionsThe incidence of SPI in hospitalized COVID-19 patients was 5%. Lower nadir median lymphocyte count during hospitalization was associated with an increased OR of developing SPI. The CRP and d-dimer levels on admission, and peak procalcitonin and CRP levels during hospitalization were higher in patients with SPI.

Effects of perinatal HIV-infection on the cortical thickness and subcortical gray matter volumes in young adulthood.

Brain atrophy has been observed in perinatally HIV-infected patients (PHIV) despite initiation on combined antiretroviral treatment (cART), but neuroimaging studies are limited. We aimed to evaluate cortical thickness (CT) and subcortical gray matter (GM) volumes of PHIV youths with stable immunovirological situation and with a normal daily performance.A prospective cross-sectional study was conducted. A total of 25 PHIV patients on cART and 25 HIV-negative (HIV-) controls matched by age, sex, level of education, and socioeconomic status underwent a magnetic resonance imaging scan. CAT12 toolbox was used to extract CT values from T1w images using parcellations from Desikan–Killiany atlas (DK40). To measure regional brain volumes, native segmented images were parceled in regions of interest according to the Neuromorphometrics Atlas. Neuropsychological assessment and psychopathological symptoms were documented.Fifty participants were included (60% females, median age 20 years [interquartile range, IQR 19–23], 64% Whites). No differences regarding neuropsychological tests or psychopathological symptoms were found between groups (all P > .05). All participants presented an average performance in the Fluid Intelligence (FI) test (PHIV mean: −0.12, HIV- mean: 0.24), When comparing CT, PHIV-infected patients showed thinner cortices compared with their peers in fusiform gyrus (P = .000, P = .009), lateral-orbitofrontal gyrus (P = .006, P = .0024), and right parsobitalis gyrus (P = .047). Regarding subcortical GM volumes, PHIV patients showed lower right amygdala (P = .014) and left putamen (P = .016) volumes when compared with HIV- controls. Within the PHIV group, higher CD4 count was associated with higher volumes in right putamen (B = 0.00000038, P = .045). Moreover, increased age at cART initiation and lower nadir CD4 count was associated with larger volumes in left accumbens (B = 0.0000046, P = .033; B = −0.00000008, P = .045, respectively).PHIV patients showed thinner cortices of areas in temporal, orbito-frontal and occipital lobes and lower volumes of subcortical GM volumes when compared with the HIV- control group, suggesting cortical and subcortical brain alterations in otherwise neuroasymptomatic patients. Nevertheless, larger and longitudinal studies are required to determine the impact of HIV on brain structure in PHIV patients and to further identify risk and protective factors that could be implicated.

Absolute Neutrophil Count after the First Chemotherapy Cycle as a Surrogate Marker for Treatment Outcomes in Patients with Neuroblastoma.

PurposeWe performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma.Materials and MethodsThe study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed.ResultsAn ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC.ConclusionIn neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

Low central blood pressure and sympathetic activity predispose for the development of intradialytic hypotension.

Intradialytic hypotension (IDH) may lead to a poor life quality and was associated with cardiovascular mortality in patients under hemodialysis. This study investigated the autonomic nerve and cardiovascular function in the IDH episodes.In this case-control study, 70 end stage renal disease patients (198 visits) were recruited. Pulse wave analysis and heart rate variability were evaluated before hemodialysis. Two definitions of IDH were confirmed by medical records. IDH-f indicated a drop of systolic blood pressure or mean arterial pressure, accompanied with symptoms; IDH-n indicated a low nadir systolic pressure during the hemodialysis. All parameters were evaluated for the possible predisposing factors under each definition.A total of 24 IDH-f and 37 IDH-n were noted in 177 visits. For both definitions, central pulse pressure seemed to be a consistent predisposing factor. Furthermore, lower sympathetic activity (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.35–0.87), lower pulse pressure (OR 0.95; 95% CI 0.92–0.98), and higher augmentation index (OR 17.36; 95% CI 1.48–204.10) were the possible predisposing factors for IDH-f. On the contrary, lower mean arterial pressure (OR 0.87; 95% CI 0.78–0.98) was identified as the possible factor for IDH-n.It was suggested that the lower central pulse pressure and sympathetic activity might be involved in the development of IDH.

Rapid eye movement sleep and slow wave sleep rebounded and related factors during positive airway pressure therapy

This study aimed to investigate the clinical characteristics and predictors of increased rapid eye movement (REM) sleep or slow wave sleep (SWS) in patients with obstructive sleep apnea (OSA) following positive airway pressure (PAP) therapy. The study retrospectively analyzed data from patients with OSA who underwent both diagnostic polysomnography (PSG) and pressure titration PSG at the Tangdu Hospital Sleep Medicine Center from 2011–2016. Paired diagnostic PSG and pressure titration studies from 501 patients were included. REM rebound was predicted by a higher oxygen desaturation index, lower REM proportion, higher arousal index, lower mean pulse oxygen saturation (SpO2), higher Epworth sleepiness score and younger age (adjusted R2 = 0.482). The SWS rebound was predicted by a longer total duration of apneas and hypopneas, lower N3 duration, lower SpO2 nadir, lower REM proportion in diagnostic PSG and younger age (adjusted R2 = 0.286). Patients without REM rebound or SWS rebound had a high probability of comorbidities with insomnia and mood complaints. Some parameters (subjective and objective insomnia, excessive daytime sleepiness, age and OSA severity) indicate changes in REM sleep and SWS between diagnostic and titration PSG tests. Treatment of insomnia and mood disorders in patients with OSA may helpful to improve the use PAP.

Brief Report: Heplisav-B Seroprotection in People With HIV: A Single-Center Experience.

Heplisav-B, a hepatitis B virus (HBV) vaccine with an immunostimulatory adjuvant, was FDA approved in 2017 for adults ≥18 years. In randomized controlled trials, Heplisav-B demonstrated seroprotection rates (SPR) of 90%-95% versus 65%-80% for Engerix-B. No studies have included people with HIV (PWH), and the SPR and its predictors in this population are unknown. Quaternary care center HIV clinic. This retrospective cohort study evaluated PWH aged ≥18 years without current HBV seroprotection (anti-HBV surface antibody level [anti-HBs] <10 mIU/mL) who were administered Heplisav-B. Patients without post-immunization titers were excluded. The primary outcome was the SPR, the proportion of participants with HBV seroprotection at any point after the first vaccination. Among 64 PWH included, median time to anti-HBs measurement after vaccination was 13 weeks. The median age was 58 years, 81% were men, and 95% had a viral load <200. The SPR was 81% in the entire cohort (and 86% in those without significant non-HIV immunosuppression), 79% in those with no prior HBV vaccination and no anti-HBc positivity, and 84% in those with prior vaccine nonresponse. Lower current and nadir CD4+ counts were associated with progressively lower seroprotection. In the first single-center retrospective study of Heplisav-B in PWH, the SPR compared favorably with the SPR seen among PWH from prior HBV vaccines across key subgroups. Given these findings, Heplisav-B should be considered for expanded use for HBV vaccination in PWH. Further research on the effectiveness of a repeat vaccination series or higher dosing in nonresponders is needed.

Associations of GNAS Mutations with Surgical Outcomes in Patients with Growth Hormone-Secreting Pituitary Adenoma.

BackgroundThe guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics.MethodsWe studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor.ResultsGNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively).ConclusionGNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.

Evaluation of Tp-e interval and Tp-e: QT and Tp-e: QTc ratios in patients infected with HIV and using antiretroviral therapy

Sudden cardiac death (SCD) is one of the causes of death among patients infected with human immunodeficiency virus (HIV). The T peak to T end interval (Tp-e interval) is a parameter that is used in the prediction of SCD. The aim of this study was to investigate the difference in Tp-e interval and Tp: QT and Tp: corrected QT interval (QTc) ratios between patients infected with HIV and healthy individuals as well as in other factors affecting patients infected with HIV.A total of 83 patients infected with HIV with negative HIV ribonucleic acid (RNA) levels who were receiving antiretroviral therapy (ART) and 83 healthy individuals were included in this study. All the participants underwent electrocardiography, their Tp-e and QT intervals were measured, and QTc intervals and Tp-e: QT and Tp-e: QTc ratios were calculated. In addition, in the patients infected with HIV, CD4 and CD8 T-cell count and HIV RNA levels were measured.The Tp-e interval was found to be longer and the Tp-e: QT and Tp-e: QTc ratios were found to be higher in patients infected with HIV. Nadir CD4 was observed to be an independent predictor of Tp-e interval (p=0.014, β=‒0.28). Furthermore, correlation analysis revealed a negative correlation of the nadir CD4 level and CD4: CD8 ratio with Tp-e interval and Tp-e: QT ratio.Low nadir CD4 and a reversed CD4: CD8 ratio in patients infected with HIV receiving ART were found to be associated with a prolonged Tp-e interval and increased Tp-e: QT and Tp-e: QTc ratios. Thus, more attention should be taken in terms of SCD in patients infected with HIV, especially in those with low nadir CD4 and reversed CD4: CD8 ratio.

Factors associated with estrous expression and subsequent fertility in lactating dairy cows using automated activity monitoring

The objective of this observational study was to identify factors associated with estrous duration (DU) and intensity measured as the peak of activity (PA) change and subsequent fertility in lactating Holstein cows using a neck-mounted automated activity monitor (Heatime Pro, SCR Engineers Ltd., Netanya, Israel). Ambient temperature and relative humidity were recorded hourly to calculate the temperature-humidity index (THI). A total of 5,933 estrus events from 3,132 cows located on 8 commercial dairy farms in Germany were used for this study. Farms participated in monthly DHIA testing. Pregnancy diagnosis was performed either by transrectal palpation [farm 1: 42 ± 3 d; farm 3: 40 ± 3 d; farms 4 and 8: 38 ± 3 d; farm 5: 43 ± 3 d after artificial insemination (AI)] or transrectal ultrasonography (farms 2, 6, and 7: 30 ± 3 d after AI). Estrous intensity was categorized based on peak activity of estrus into low (35-89 index value), and high (90-100 index value) PA. Overall, 73.5% of estrus events were of high PA. The mean (± standard error of the mean) DU was 14.94 ± 0.06 h. There was a strong correlation between DU and PA (r = 0.67). In the final statistical model, only PA was associated with pregnancy per artificial insemination (P/AI), with 1.35 greater odds of pregnancy for cows with high PA compared with cows with low PA. Increased THI 1 wk before AI was associated with shorter DU, lower PA, and decreased P/AI. A small percentage of cows (4.7%) showed short interestrus intervals (i.e., more than 1 activity peak within 7 d close to the event of estrus), resulting in reduced DU, PA, and P/AI. The change of weighted rumination was associated with DU and PA, as a lower nadir was associated with a greater risk for high PA and long DU. There was no association, however, between the nadir of change of weighted rumination and P/AI. Whereas milk yield and somatic cell count from the DHIA test date before AI were negatively associated with estrous expression, neither milk yield nor somatic cell count was associated with P/AI. Surprisingly, multiparous cows expressed estrus with longer DU (13.15 ± 0.31 h) compared with primiparous cows (12.52 ± 0.32 h), whereas PA did not differ among parities. Pregnancy per AI was greater for primiparous (29.4%) than for multiparous (22.1%) cows. An estrus event with long DU or high PA was more likely later in lactation. Milk fat, milk protein, milk urea nitrogen, and lactose from the DHIA test date closest to AI had no association with estrous expression or P/AI. In conclusion, DU and PA were highly correlated, and cows with high PA were particularly associated with greater odds for pregnancy. A negative association between estrous expression and P/AI was identified for increased THI 1 wk before AI and cows with short interestrus intervals using automated activity monitor.

Underfrequency Load Shedding Using Locally Estimated RoCoF of the Center of Inertia

The conventional Under Frequency Load Shedding (UFLS) scheme could result in unacceptably low frequency nadirs or overshedding in power systems with volatile inertia. This paper proposes a novel UFLS scheme for modern power systems whose inertia may vary in a wide range due to high penetration of renewable energy sources (RESs). The proposed scheme estimates the rate of change of frequency (RoCoF) of the center of inertia (CoI), and consequently, the loss of generation (LoG) size, using local frequency measurements only. An innovative inflection point detector technique is presented to remove the effect of local frequency oscillations. This enables fast and accurate LoG size calculation, thereby more effective load shedding. The proposed UFLS scheme also accounts for the effect of the inertia change resulting from LoG events. The performance of the proposed scheme is validated by conducting extensive dynamic simulations on the IEEE 39-bus test system using Real Time Digital Simulator (RTDS). Simulation results confirm that the proposed UFLS scheme outperforms the conventional UFLS scheme in terms of both arresting frequency deviations and the amount of load shed.

Risk factors for ≥high-grade anal intraepithelial lesions in MSM living with HIV and the response to topical and surgical treatments.

BackgroundThe objective of this study in MSM living with HIV was to determine the incidence of HSIL and ASCC, related factors, and the response to treatment.Patients and methodsData were gathered in 405 consecutive HIV-infected MSM (May 2010-December 2018) at baseline and annually on: sexual behavior, anal cytology, and HPV PCR and/or high-resolution anoscopy results. They could choose mucosectomy with electric scalpel (from May 2010) or self-administration of 5% imiquimod 3 times weekly for 16 weeks (from November 2013). A multivariate logistic regression model was developed for ≥HSIL-related factors using a step-wise approach to select variables, with a significance level of 0.05 for entry and 0.10 for exit, applying the Hosmer-Lemeshow test to assess the goodness of fit.ResultsThe study included 405 patients with a mean age of 36.2 years; 56.7% had bachelor´s degree, and 52.8% were smokers. They had a mean of 1 (IQR 1–7) sexual partner in the previous 12 months, median time since HIV diagnosis of 2 years, and mean CD4 nadir of 367.9 cells/uL; 86.7% were receiving ART, the mean CD4 level was 689.6 cells/uL, mean CD4/CD8 ratio was 0.77, and 85.9% of patients were undetectable. Incidence rates were 30.86/1,000 patient-years for ≥high squamous intraepithelial lesion (HSIL) and 81.22/100,000 for anal squamous cell carcinoma (ASCC). The ≥HSIL incidence significantly decreased from 42.9% (9/21) in 2010 to 4.1% (10/254) in 2018 (p = 0.034). ≥HSIL risk factors were infection with HPV 11 (OR 3.81; 95%CI 1.76–8.24), HPV 16 (OR 2.69, 95%CI 1.22–5.99), HPV 18 (OR 2.73, 95%CI 1.01–7.36), HPV 53 (OR 2.97, 95%CI 1.002–8.79); HPV 61 (OR 11.88, 95%CI 3.67–38.53); HPV 68 (OR 2.44, CI 95% 1.03–5.8); low CD4 nadir (OR1.002; 95%CI 1–1.004) and history of AIDS (OR 2.373, CI 95% 1.009–5.577). Among HSIL-positive patients, the response rate was higher after imiquimod than after surgical excision (96.7% vs 73.3%, p = 0.009) and there were fewer re-treatments (2.7% vs 23.4%, p = 0.02) and adverse events (2.7% vs 100%, p = 0.046); none developed ASCC.ConclusionsHSIL screening and treatment programs reduce the incidence of HSIL, which is related to chronic HPV infection and poor immunological status. Self-administration of 5% imiquimod as first-line treatment of HSIL is more effective than surgery in HIV+ MSM.

1059 Examining the association of antepartum anemia on cesarean morbidity

Pre-operative anemia has been associated with increased morbidity in the gynecologic surgery literature, however there is limited data examining the association of anemia in pregnancy and morbidity after cesarean delivery. Our hypothesis is women with antepartum anemia have a higher morbidity after cesarean delivery compared to women without anemia. This is retrospective cohort at Women & Infants Hospital in 2019 including women with singleton pregnancies undergoing cesarean delivery after 37 weeks gestation. Women were excluded with hemoglobinopathies or bleeding disorders. The continuous variables were compared using Student’s t-test or Wilcoxon rank-sum; Fisher’s exact test was used to compare categorical variables. Anemia was defined as hemoglobin (hgb) less than 11 g/dL. Our primary outcome was composite of maternal morbidity comparing women with and without anemia on admission who has cesarean delivery. We predicted 294 women with 2:1 ratio non-anemic vs anemic would afford power of 80% to detect a difference of 5 to 15% in our primary outcome with alpha of 0.05. In our cohort 223 women, 18.3% were anemic on admission for delivery. There was no significant difference in composite maternal (17.1% vs 14.8% p=0.81) for anemic versus non-anemic populations (Table 1). The average hgb in the anemic versus non-anemic groups on admission were respectively 12.3+0.85 and 10.3+0.53 g/dL. Women who were anemic at delivery were more likely to have begun pregnancy with a lower hemoglobin (11.6 versus 12.5; p<0.001), and have a lower hemoglobin nadir during pregnancy (10.0 versus 11.4; p<0.001). Black women (p=0.04) and multiparous women (p=0.02) were more likely to be anemic at time of delivery. Anemia was not associated with maternal morbidity after cesarean delivery, however this study was underpowered. The risk of anemia was varied by race with black women having higher rate of anemia. This finding should be further investigated to determine the reasons behind this disparity in care.

Comparison of procedural efficacy and biophysical parameters between two competing cryoballoon technologies for pulmonary vein isolation: Insights from an initial multicenter experience.

IntroductionRecently a novel cryoballoon system (POLARx, Boston Scientific) became available for the treatment of atrial fibrillation. This cryoballoon is comparable with Arctic Front Advance Pro (AFA‐Pro, Medtronic), however, it maintains a constant balloon pressure. We compared the procedural efficacy and biophysical characteristics of both systems.MethodsOne hundred and ten consecutive patients who underwent first‐time cryoballoon ablation (POLARx: n = 57; AFA‐Pro: n = 53) were included in this prospective cohort study.ResultsAcute isolation was achieved in 99.8% of all pulmonary veins (POLARx: 99.5% vs. AFA‐Pro: 100%, p = 1.00). Total procedure time (81 vs. 67 min, p < .001) and balloon in body time (51 vs. 35 min, p < .001) were longer with POLARx. After a learning curve, these times were similar. Cryoablation with POLARx was associated with shorter time to balloon temperature −30°C (27 vs. 31 s, p < .001) and −40°C (32 vs. 54 s, p < .001), lower balloon nadir temperature (−55°C vs. −47°C, p < .001), and longer thawing time till 0°C (16 vs. 9 s, p < .001). There were no differences in time‐to‐isolation (TTI; POLARx: 45 s vs. AFA‐Pro 43 s, p = .441), however, POLARx was associated with a lower balloon temperature at TTI (−46°C vs. −37°C, p < .001). Factors associated with acute isolation differed between groups. The incidence of phrenic nerve palsy was comparable (POLARx: 3.5% vs. AFA‐Pro: 3.7%).ConclusionThe novel cryoballoon is comparable to AFA‐Pro and requires only a short learning curve to get used to the slightly different handling. It was associated with faster cooling rates and lower balloon temperatures but TTI was similar to AFA‐Pro.

Mechanisms Underlying Glycemic Reduction Following Roux-en-Y Gastric Bypass Surgery: Foregut Versus Hindgut Contributions

Background: Roux-en-Y gastric bypass (RYBG) cures type 2 diabetes in over 80% of cases, although the mechanisms remain incompletely understood. A primary role for exaggerated secretion of glucagon-like peptide-1 (GLP-1) from the hindgut has been established, however the question remains whether omission of an as-yet uncharacterized diabetogenic foregut factor may also contribute. The “foregut hypothesis” derives from a study by Rubino et al. in which glycemic responses to hindgut feeding in duodenal-jejunal bypassed rats (analogous to RYGB anatomy), foregut feeding in gastrojejunal anastomosed rats, and foregut+hindgut feeding in sham-operated pair-fed controls showed that foregut stimulation independently raised blood glucose while bypassing the foregut lowered glucose. We performed a human study analogous to the Rubino study to further evaluate this hypothesis. Methods: Four post-RYGB patients with indwelling gastrostomy-tubes (g-tubes) were fed a standardized 75 g liquid meal on three separate days under differing fasting feeding conditions: 1) isolated oral feeding to the hindgut, 2) isolated g-tube feeding to the foregut, and 3) concomitant oral+g-tube feeding (co-stimulation of foregut and hindgut). Results: Compared to g-tube feeding, oral feeing led to significantly higher glucose (217 vs. 150 mg/dL, p=0.042) and insulin peaks (304 vs. 120 μIU/mL, p=0.021) and lower glucose nadirs (43 vs. 72 mg/dL, p=0.019), while compared to isolated oral or g-tube feeding, concomitant oral+g-tube feeding led to higher glucose (255 mg/dL) and insulin peaks (452 μIU/mL), and higher glucose nadirs (78 mg/dL). Conclusion: Hindgut stimulation and foregut omission may independently contribute to glucose lowering after RYGB.

Combination of positional therapy with positive airway pressure for titration in patients with difficult to treat obstructive sleep apnea

Positional therapy has been described as add-on therapy to a mandibular advancement device, but the efficacy of combination of positional therapy and positive airway pressure (PPAP) has not been documented. We have found PPAP therapy as an effective method of titration in patients with difficult to treat OSA (obstructive sleep apnea). This retrospective analysis was done in patients who had difficult to treat OSA, i.e., in whom titration in thesupine position was unacceptable with any PAP device (CPAP or bilevel PAP) and could only be successfully titrated with a PAP device in the lateral position. This study describes our experience of PPAP therapy. Baseline characteristics and polysomnography data of patients who were successfully titrated in supine v/s lateral positions were compared. Of 272 consecutive patients with OSA selected for analysis, 218 patients (191 and 27 with CPAP and bilevel PAP, respectively) could be successfully titrated in supine position. Further 54 (20%) patients in whom titration in supine position was unacceptable were titrated in lateral position. Patients titrated with PAP in the lateral position therapy group had higher BMI, higher neck and waist circumference, and lower awake sPO2 and nadir sPO2 during sleep, and spent more time in sleep with sPO2 < 90%. Combination of positional therapy and PAP device is an effective way of titration for difficult to treat OSA patients. It can be tried in patients who fail titration in supine position.

Viral protein R polymorphisms in the pathogenesis of HIV-associated acute ischaemic stroke: a case-control study.

HIV-1 viral proteins have been implicated in endothelial dysfunction, which is a major determinant of ischaemic stroke risk in HIV-infected individuals. Polymorphisms in HIV-1 viral protein R (Vpr) may alter its potential to promote endothelial dysfunction, by modifying its effects on viral replication, reactivation of latent cells, upregulation of pro-inflammatory cytokines and infection of macrophages. We analysed Vpr polymorphisms and their association with acute ischaemic stroke by comparing Vpr signature amino acids between 54 HIV-infected individuals with acute ischaemic stroke, and 80 age-matched HIV-infected non-stroke controls. Isoleucine at position 22 and serine at position 41 were associated with ischaemic stroke in HIV. Individuals with stroke had lower CD4 counts and CD4 nadirs than controls. These polymorphisms are unique to individuals with stroke compared to South African subtype C and the control group consensus sequences. Signature Vpr polymorphisms are associated with acute ischaemic stroke in HIV. These may increase stroke risk by promoting endothelial dysfunction and susceptibility to opportunistic infections. Therapeutic targeting of HIV-1 viral proteins may present an additional mechanism of decreasing stroke risk in HIV-infected individuals.