Frequency and Distribution of Ophthalmic Surgical Procedures among Patients with Inherited Retinal Diseases.

OBJECTIVE: In this study, we aimed to characterize the frequency and distribution of ocular surgeries in patients with inherited retinal diseases (IRDs) and evaluate associated patient and disease factors. DESIGN: Retrospective cohort. PARTICIPANTS: Subjects aged ≥ 18 years who were followed at the Johns Hopkins Genetic Eye Disease Center. METHODS: We studied a retrospective cohort of patients with an IRD diagnosis to analyze the occurrence of laser and incisional surgeries. Subjects were categorized into 2 groups: central dysfunction (macular/cone/cone-rod dystrophy, "MCCRD group") and panretinal or peripheral dysfunction (retinitis pigmentosa-like, "RP group"). Genetic testing status was recorded. The association of patient and disease factors on the frequency, distribution, and timing of surgeries was analyzed. MAIN OUTCOME MEASURES: Prevalence, prevalence odds ratio (POR), hazard ratio (HR) of ophthalmic procedures by phenotype. RESULTS: A total of 1472 eyes of 736 subjects were evaluated. Among them, 31.3% (n = 230) had undergone ocular surgery, and 78.3% of those (n = 180/230) had a history of more than 1 surgery. A total of 602 surgical procedures were analyzed. Cataract extraction with intraocular lens implantation (CEIOL) was the most common (51.2%), followed by yttrium aluminum garnet capsulotomy, refractive surgery, retinal surgery, and others. Cataract extraction with intraocular lens implantation occurred more frequently in RP than in MCCRD subjects (POR, 2.59; P = 0.002). Retinitis pigmentosa subjects underwent CEIOL at a younger age than patients with MCCRD (HR, 2.11; P < 0.001). CONCLUSIONS: Approximately one-third of patients with IRD had a history of laser or incisional surgery. Cataract extraction with intraocular lens implantation was the most common surgery; its frequency and timing may be associated with the IRD phenotype. This data may inform the design of prospective research. Such efforts may illuminate routine clinical decision-making and contribute to surgical strategy development for cell and gene therapy delivery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

HIF-1α inhibition in macrophages preserves acute liver failure by reducing IL-1ß production.

The development of acute liver failure (ALF) is dependent on its local inducer. Inflammation is a high-frequency and critical factor that accelerates hepatocyte death and liver failure. In response to injury stress, the expression of the transcription factor hypoxia-inducible factor-1α (HIF-1α) in macrophages is promoted by both oxygen-dependent and oxygen-independent mechanisms, thus promoting the expression and secretion of the cytokine interleukin-1ß (IL-1ß). IL-1ß further induces hepatocyte apoptosis or necrosis by signaling through the receptor (IL-1R) on hepatocyte. HIF-1α knockout in macrophages or IL-1R knockout in hepatocytes protects against liver failure. However, whether HIF-1α inhibition in macrophages has a protective role in ALF is unclear. In this study, we revealed that the small molecule HIF-1α inhibitor PX-478 inhibits the expression and secretion of IL-1ß, but not tumor necrosis factor α (TNFα), in bone marrow-derived macrophages (BMDMs). PX-478 pretreatment alleviates liver injury in LPS/D-GalN-induced ALF mice by decreasing the hepatic inflammatory response. In addition, preventive or therapeutic administration of PX-478 combined with TNFα neutralizing antibody markedly improved LPS/D-GalN-induced ALF. Taken together, our data suggest that PX-478 administration leads to HIF-1α inhibition and decreased IL-1ß secretion in macrophages, which represents a promising therapeutic strategy for inflammation-induced ALF.

Perinatal Factors and Emotional, Cognitive, and Behavioral Dysregulation in Childhood and Adolescence.

OBJECTIVE: This cohort study assessed perinatal factors known to be related to maternal and neonatal inflammation and hypothesized that several would be associated with emotional, cognitive, and behavioral dysregulation in youth. METHOD: The Environmental influences on Child Health Outcomes (ECHO) is a research consortium of 69 pediatric longitudinal cohorts. A subset of 18 cohorts that had both Child Behavior Checklist (CBCL) data on children (6-18 years) and information on perinatal exposures including maternal prenatal infections was used. Children were classified as having the CBCL-Dysregulation Profile (CBCL-DP) if the sum of their T scores for 3 CBCL subscales (attention, anxious/depressed, and aggression) was ≥180. Primary exposures were perinatal factors associated with maternal and/or neonatal inflammation, and associations between these and outcome were assessed. RESULTS: Approximately 13.4% of 4,595 youth met criteria for CBCL-DP. Boys were affected more than girls (15.1% vs 11.5%). More youth with CBCL-DP (35%) were born to mothers with prenatal infections compared with 28% of youth without CBCL-DP. Adjusted odds ratios indicated the following were significantly associated with dysregulation: having a first-degree relative with a psychiatric disorder; being born to a mother with lower educational attainment, who was obese, had any prenatal infection, and/or who smoked tobacco during pregnancy. CONCLUSION: In this large study, a few modifiable maternal risk factors with established roles in inflammation (maternal lower education, obesity, prenatal infections, and smoking) were strongly associated with CBCL-DP and could be targets for interventions to improve behavioral outcomes of offspring. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Lung Cancer Recurrence Risk Prediction through Integrated Deep Learning Evaluation.

Background: Prognostic risk factors for completely resected stage IA non-small-cell lung cancers (NSCLCs) have advanced minimally over recent decades. Although several biomarkers have been found to be associated with cancer recurrence, their added value to TNM staging and tumor grade are unclear. Methods: Features of preoperative low-dose CT image and histologic findings of hematoxylin- and eosin-stained tissue sections of resected lung tumor specimens were extracted from 182 stage IA NSCLC patients in the National Lung Screening Trial. These features were combined to predict the risk of tumor recurrence or progression through integrated deep learning evaluation (IDLE). Added values of IDLE to TNM staging and tumor grade in progression risk prediction and risk stratification were evaluated. Results: The 5-year AUC of IDLE was 0.817 ± 0.037 as compared to the AUC = 0.561 ± 0.042 and 0.573 ± 0.044 from the TNM stage and tumor grade, respectively. The IDLE score was significantly associated with cancer recurrence (p < 0.0001) even after adjusting for TNM staging and tumor grade. Synergy between chest CT image markers and histological markers was the driving force of the deep learning algorithm to produce a stronger prognostic predictor. Conclusions: Integrating markers from preoperative CT images and pathologist's readings of resected lung specimens through deep learning can improve risk stratification of stage 1A NSCLC patients over TNM staging and tumor grade alone. Our study suggests that combining markers from nonoverlapping platforms can increase the cancer risk prediction accuracy.

Multi­institutional development and validation of a nomogram to predict prognosis of early-onset gastric cancer patients.

Background: Early-onset gastric cancer (EOGC, ≤45 years old) is characterized with increasing incidence and more malignant phenotypes compared with late-onset gastric cancer, which exhibits remarkable immune cell infiltration and is potential immunotherapeutic population. Till now, restricted survival information of EOGC is available due to limited case numbers. This study established a novel nomogram to help evaluate cancer-specific survival (CSS) of EOGC patients who underwent gastrectomy, and may provide evidence for predicting patients' survival. Methods: We retrospectively enrolled a cohort containing 555 EOGC cases from five independent medical centers in China, among which 388 cases were randomly selected into a training set while the other 167 cases were assigned into the internal validation set. Asian or Pacific Islander (API) patients diagnosed with EOGC during 1975-2016 were retrieved from the SEER database (n=299) and utilized as the external validation cohort. Univariate and multivariate analyses were conducted to test prognostic significances of clinicopathological factors in the training set. Accordingly, two survival nomogram models were established and compared by concordance index (C-index), calibration curve, receiver operating characteristics (ROC) curves and decision curve analyses (DCA). Results: The 5-year CSS rate of training cohort was 61.3% with a median survival time as 97.2 months. High consistency was observed on calibration curves in all three cohorts. Preferred nomogram was selected due to its better performance on ROC and DCA results. Accordingly, a novel predicative risk model was introduced to better stratify high-risk EOGC patients with low-risk patients. In brief, the 5-year CSS rates for low-risk groups were 92.9% in training set, 83.1% in internal validation set, 89.9% in combined NQSQS cohort, and 85.3% in SEER-API cohort. In contrast, the 5-year CSS rates decreased to 38.5%, 44.3%, 40.5%, and 36.9% in the high-risk groups of the four cohorts above, respectively. The significant survival difference between high-risk group (HRG) and low-risk group (LRG) indicated the precise accuracy of our risk model. Furthermore, the risk model was validated in patients with different TNM stages, respectively. Finally, an EOGC web-based survival calculator was established with public access, which can help predict prognosis. Conclusions: Our data provided a precise nomogram on predicting CSS of EOGC patients with potential clinical applicability.

Analysis of Early-Life Growth and Age at Pubertal Onset in US Children.

Importance: Earlier pubertal onset may be associated with an increased risk of chronic diseases. However, the extent to which growth in the first 5 years of life-an important developmental life stage that lays the foundation for later health outcomes-is associated with pubertal onset remains understudied. Objective: To assess whether changes in weight, length or height, and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) during the first 5 years of life are associated with earlier pubertal onset. Design, Setting, and Participants: This cohort study used data from 36 cohorts participating in the Environmental Influences on Child Health Outcomes program from January 1, 1986, to December 31, 2015. Participant inclusion required at least 1 anthropometric measure in the first 5 years of life and at least 1 measure of pubertal onset. Data were analyzed from January 1 to June 30, 2021. Exposures: Standardized velocities of weight, length or height, and BMI gain in early infancy (0-0.5 years), late infancy (0.5-2 years), and early childhood (2-5 years). Main Outcomes and Measures: Markers of pubertal onset for boys and girls, including age at peak height velocity (APHV), time to puberty score greater than 1, time to Tanner pubic hair stage greater than 1, and time to menarche. Multivariable regression models were used to estimate mean differences in APHV by growth periods. Results: Of 7495 children included in the study, 3772 (50.3%) were girls, 4505 (60.1%) were White individuals, and 6307 (84.1%) were born during or after the year 2000. Girls had a younger APHV (10.8 vs 12.9 years) than boys. In boys, faster weight gain (per 1-SD increase) in early infancy (ß, -0.08 years; 95% CI, -0.10 to -0.06), late infancy (ß, -0.10 years; 95% CI, -0.12 to -0.08), and early childhood (ß, -0.07 years; 95% CI, -0.08 to -0.05) was associated with younger APHV after adjusting for the child's birth year, race, and Hispanic ethnicity as well as maternal age at delivery; educational level during pregnancy; annual household income during pregnancy; prenatal cigarette smoking; whether the mother was nulliparous; whether the mother had gestational diabetes, hypertension, or preeclampsia; mode of delivery; prepregnancy BMI; gestational weight gain; and gestational age at delivery. Similar associations were observed for length or height and BMI gains during the same age periods. In girls, faster gains (per 1-SD increase) in weight (ß, -0.03 years; 95% CI, -0.05 to -0.01) and height (ß, -0.02 years; 95% CI, -0.04 to 0.00) in early childhood were associated with younger APHV. Faster BMI gain in late infancy was associated with earlier time to menarche, whereas faster BMI gain in early childhood was associated with earlier time to Tanner pubic hair stage greater than 1. Conclusions and Relevance: This cohort study found that faster gains in weight, length or height, or BMI in early life were associated with earlier pubertal onset. The results suggest that children who experience faster early growth should be monitored closely for earlier onset of puberty and referred as appropriate for supportive services.

Disparities in the uptake of digital breast tomosynthesis for breast cancer screening: A retrospective cohort study.

We present a retrospective cohort study evaluating the utilization and effectiveness of digital breast tomosynthesis (DBT) for breast cancer screening with a focus on racial differences. 46,236 females underwent screening mammography between 4/1/2013 and 3/30/2020, during which there was an increase in DBT utilization from 18.8% in year 1 to 89.6% in year 7. Black and Asian women were significantly less likely to have a screening study with DBT compared to White women. Overall, the DBT group had a lower recall rate (9.1% versus 11.2%, p < 0.001) and higher cancer detection rate (6.0 vs 4.1, p < 0.001) compared to the FFDM group.

Locus-Level Changes in Macular Sensitivity in Patients with Retinitis Pigmentosa Treated with Oral N-acetylcysteine.

PURPOSE: To identify characteristics of loci associated with locus-level sensitivity loss or improvement during treatment with N-acetylcysteine (NAC) in retinitis pigmentosa (RP). DESIGN: Retrospective analysis of prospectively collected data in the FIGHT RP clinical trial. METHODS: Patients (n = 30) were treated with 600, 1,200, or 1,800 mg of NAC twice daily for 3 months and then 3 times/day for 3 months. Microperimetry locus-level changes between baseline and month 6 were correlated with baseline characteristics of loci using regression models. The main outcome measurement was locus-level sensitivity change ≥6 dB. RESULTS: Baseline mean sensitivity (3,468 loci; 51 evaluable eyes) was 7.7 dB and for foveal, parafoveal, and perifoveal loci were 20.2, 11.8, and 5.8 dB. During treatment, 287 loci (8.28%) increased ≥6 dB, and 119 of 1,613 loci with baseline sensitivity ≥6 dB decreased ≥6 dB (7.38%). A higher dose of NAC was associated with lower likelihood of sensitivity loss ≥6 dB (P = .033). Loci with low baseline sensitivity were more likely to decrease ≥6 dB (P = .034) but also more likely to increase ≥6 dB (P < .001). Foveal versus perifoveal loci (P < .001) and superior versus inferior loci (P = .005) were more likely to increase ≥6 dB. CONCLUSIONS: Higher doses of NAC reduced risk of macular loci sensitivity loss in RP. Greater sensitivity depression reversibility in the fovea during treatment suggests that high foveal cone density protects cones from irreversible loss of function in RP making them more likely to show improved function during NAC treatment.

Incidence, risk factors and clinical outcomes of acute kidney injury after heart transplantation: a retrospective single center study.

OBJECTIVES: This study aimed to identify the incidence rate of Acute kidney injury (AKI) in our center and predict in-hospital mortality and long-term survival after heart transplantation (HTx). METHODS: This single-center, retrospective study from October 2009 and March 2020 analyzed the pre-, intra-, and postoperative characteristics of 95 patients who underwent HTx. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Risk factors were analyzed by multivariable logistic regression models. The log-rank test was used to compare long-term survival. RESULTS: Thirty-three (34.7%) patients developed AKI. The mortality in hospital in HTx patients with and without AKI were 21.21 and 6.45%, respectively (P < 0.05). Recipients in AKI who required renal replacement therapy (RRT) had a hospital mortality rate of 43.75% compared to 6.45% in those without AKI or RRT (P < 0.0001). A long cardiopulmonary bypass (CPB) time (OR:11.393, 95% CI: 2.183 to 59.465, P = 0.0039) was positively related to the occurrence of AKI. A high intraoperative urine volume (OR: 0.031, 95% CI: 0.005 to 0.212, P = 0.0004) was negatively correlated with AKI. AKI requiring RRT (OR, 11.348; 95% CI, 2.418-53.267, P = 0.002) was a risk factor for mortality in hospital. Overall survival in patients without AKI at 1 and 3 years was not different from that in patients with AKI (P = 0.096). CONCLUSIONS: AKI is common after HTx. AKI requiring RRT could contribute powerful prognostic information to predict mortality in hospital. A long CPB time and low intraoperative urine volume are associated with the occurrence of AKI.

Prevalence and Consequences of Perceived Vision Difficulty in Aging Adults with HIV Infection.

PURPOSE: Despite well-known ocular complications of HIV-related immune suppression, few studies have examined the prevalence and consequences of visual impairment among aging long-term survivors of HIV. DESIGN: Retrospective cohort study. METHODS: Aging HIV-infected (HIV+) men who have sex with men (MSM) and HIV-uninfected (HIV-) MSM controls reported their difficulty performing 6 vision-dependent tasks (difficulty defined as: no, a little, moderate, and extreme difficulty). Relationships were examined using logistic regression, regressing each outcome separately on categorical visual function responses, with missing data multiply imputed. RESULTS: There were 634 age-matched pairs for a total sample of 1,268 MSM of 1,700 MSM with available data. The median age was 60 years old (interquartile range [IQR], 54, 66), and 23% were African American. Among HIV+ men, 95% were virally suppressed (viral load <400 copies/mL). HIV+ men were more likely to report moderate or extreme difficulty performing at least 1 task (21% for HIV+ compared to 13% for HIV-; P < .01). Participants reporting extreme vision-related difficulty performing at least 1 task had 11.2 times the odds of frailty (95% confidence interval [CI], 5.2-23.9), 2.6 times the odds of a slow gait speed (95% CI, 1.4-4.8), and 3.2 times the odds of impaired instrumental activities of daily living (95% CI: 1.6-6.3) compared to those reporting no vision-related difficulty on any task. CONCLUSIONS: Perceived vision difficulty was more common among older HIV+ MSM than age-matched HIV- MSM controls and was associated with higher risk of depression and physical function loss among MSM.

Coronary artery bypass graft combined with liver transplantation in patients with advanced alcoholic liver cirrhosis: A case report.

Performing cardiothoracic surgery on patients with advanced liver failure and liver cirrhosis is high-risk for patients. Coronary artery bypass grafting is the most effective treatment for patients with liver failure that is complicated with severe coronary heart disease, and who cannot be treated using coronary stent intervention. In the current study, one case of coronary artery bypass grafting combined with liver transplantation was assessed, with the patient exhibiting advanced alcoholic liver cirrhosis. A coronary artery bypass graft was performed to relieve angina pectoris. Following surgery, wound exudation, secondary infection, liver failure, pleuroperitoneal fluid leakage, hypoproteinemia and other adverse treatment results occurred, and the chest wound did not heal. Allograft liver transplantation was subsequently performed and, following surgery, the chest wound healed gradually after debridement, and the patient recovered.

Oral N-acetylcysteine improves cone function in retinitis pigmentosa patients in phase I trial.

BACKGROUNDIn retinitis pigmentosa (RP), rod photoreceptors degenerate from 1 of many mutations, after which cones are compromised by oxidative stress. N-acetylcysteine (NAC) reduces oxidative damage and increases cone function/survival in RP models. We tested the safety, tolerability, and visual function effects of oral NAC in RP patients.METHODSSubjects (n = 10 per cohort) received 600 mg (cohort 1), 1200 mg (cohort 2), or 1800 mg (cohort 3) NAC bid for 12 weeks and then tid for 12 weeks. Best-corrected visual acuity (BCVA), macular sensitivity, ellipsoid zone (EZ) width, and aqueous NAC were measured. Linear mixed-effects models were used to estimate the rates of changes during the treatment period.RESULTSThere were 9 drug-related gastrointestinal adverse events that resolved spontaneously or with dose reduction (maximum tolerated dose 1800 mg bid). During the 24-week treatment period, mean BCVA significantly improved at 0.4 (95% CI: 0.2-0.6, P < 0.001), 0.5 (95% CI: 0.3-0.7, P < 0.001), and 0.2 (95% CI: 0.02-0.4, P = 0.03) letters/month in cohorts 1, 2, and 3, respectively. There was no significant improvement in mean sensitivity over time in cohorts 1 and 2, but there was in cohort 3 (0.15 dB/month, 95% CI: 0.04-0.26). There was no significant change in mean EZ width in any cohort.CONCLUSIONOral NAC is safe and well tolerated in patients with moderately advanced RP and may improve suboptimally functioning macular cones. A randomized, placebo-controlled trial is needed to determine if oral NAC can provide long-term stabilization and/or improvement in visual function in patients with RP.TRIAL REGISTRATIONNCT03063021.FUNDINGMr. and Mrs. Robert Wallace, Mr. and Mrs. Jonathan Wallace, Rami and Eitan Armon, Marc Sumerlin, Cassandra Hanley, and Nacuity Pharmaceuticals, Inc.

Act values after neutralization lower than pre-heparinization act leads to lower operative times, bleeding, and post-operative transfusions in cabg pa

Abstract Objective: To evaluate if lower activated coagulation time (ACT) value after neutralization than preoperative ACT value was effective in reducing bleeding, operative times, and post-operative transfusions in patients underwent coronary artery bypass grafting (CABG). Methods: Retrospective selection of 398 patients from January 2014 to May 2017. Patients were divided into 2 groups according to final ACT after neutralization: A - final ACT lower than preoperative ACT; and B - final ACT higher than or equal to preoperative ACT. Hemostatic time, intraoperative blood loss, ACT after final neutralization, mediastinal blood loss, and transfusion requirements were observed. Results: The hourly blood loss in the Group A was generally lower than in the Group B at first 3 hours, which has significant difference (P<0.05). However, there was no difference after 3 hours between the two groups. Operative time, intraoperative blood loss, mediastinal blood loss, transfusion requirements, and drainage in the first postoperative 12 hours in the Group A were lower than in Group B, which has significant difference (P<0.05). Conclusion: As a result, final ACT values lower than pre-heparinization ACT values are safe and lead to lower operative times, bleeding, and post-operative transfusions.

Outcomes Following Coronary Artery Bypass Graft Surgery in Patients with Mild Preoperative Renal Insufficiency.

INTRODUCTION: Preoperative renal insufficiency is an independent predictor of mortality after coronary artery bypass graft (CABG) surgery. However, there are few reports aimed to evaluate the impact of mild preoperative renal insufficiency on long-term follow-up outcomes after isolated CABG surgery. This study investigates the effect of mild preoperative renal insufficiency on long-term follow-up outcomes of patients after CABG. METHODS: Five hundred eighty-four patients' data that underwent CABG between 1 January 2009 and 1 December 2016 were retrospectively analyzed. They were divided into two groups: normal group [Estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m2, n=304] and mild group (eGFR ranges from 60 to 89 ml/min/1.73 m2, n=280). Clinical material and long follow-up outcomes were compared inthe two groups. RESULTS: Two groups had similar baseline and intraoperative data except eGFR. Six (0.01%) patients died in hospital, 15 in normal group and 28 in mild group during the long-term follow-up, which had statistical significance (P<0.05). Univariate factor analysis displayed that the two groups had similar in-hospital outcomes. Kaplan-Meier curves showed a better long-term survival in patients with normal preoperative renal function compared to mild preoperative renal insufficiency (x 2=4.255, P=0.039). Cox proportional model presented the hazard ratio of long-term mortality in patients with mild preoperative renal insufficiency compared to normal preoperative renal function was 1.79 (95% CI 1.17-2.88, P=0.027). CONCLUSIONS: Patients with mild preoperative renal insufficiency had a higher mortality rate than normal patients in long-term survival, whereas no evidence of worse in-hospital mortality rate was found. Patients with mild preoperative renal insufficiency showed a higher mortality rate than other studies.

Outcomes following coronary artery bypass graft surgery in patients with mild preoperative renal insufficiency

Abstract Introduction: Preoperative renal insufficiency is an independent predictor of mortality after coronary artery bypass graft (CABG) surgery. However, there are few reports aimed to evaluate the impact of mild preoperative renal insufficiency on long-term follow-up outcomes after isolated CABG surgery. This study investigates the effect of mild preoperative renal insufficiency on long-term follow-up outcomes of patients after CABG. Methods: Five hundred eighty-four patients' data that underwent CABG between 1 January 2009 and 1 December 2016 were retrospectively analyzed. They were divided into two groups: normal group [Estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m2, n=304] and mild group (eGFR ranges from 60 to 89 ml/min/1.73 m2, n=280). Clinical material and long follow-up outcomes were compared inthe two groups. Results: Two groups had similar baseline and intraoperative data except eGFR. Six (0.01%) patients died in hospital, 15 in normal group and 28 in mild group during the long-term follow-up, which had statistical significance (P<0.05). Univariate factor analysis displayed that the two groups had similar in-hospital outcomes. Kaplan-Meier curves showed a better long-term survival in patients with normal preoperative renal function compared to mild preoperative renal insufficiency (x 2=4.255, P=0.039). Cox proportional model presented the hazard ratio of long-term mortality in patients with mild preoperative renal insufficiency compared to normal preoperative renal function was 1.79 (95% CI 1.17-2.88, P=0.027). Conclusions: Patients with mild preoperative renal insufficiency had a higher mortality rate than normal patients in long-term survival, whereas no evidence of worse in-hospital mortality rate was found. Patients with mild preoperative renal insufficiency showed a higher mortality rate than other studies.

ACT Values after Neutralization Lower than Pre-heparinization ACT Leads to Lower Operative Times, Bleeding, and Post-Operative Transfusions in CABG Patients: an Observational Study.

OBJECTIVE: To evaluate if lower activated coagulation time (ACT) value after neutralization than preoperative ACT value was effective in reducing bleeding, operative times, and post-operative transfusions in patients underwent coronary artery bypass grafting (CABG). METHODS: Retrospective selection of 398 patients from January 2014 to May 2017. Patients were divided into 2 groups according to final ACT after neutralization: A - final ACT lower than preoperative ACT; and B - final ACT higher than or equal to preoperative ACT. Hemostatic time, intraoperative blood loss, ACT after final neutralization, mediastinal blood loss, and transfusion requirements were observed. RESULTS: The hourly blood loss in the Group A was generally lower than in the Group B at first 3 hours, which has significant difference (P<0.05). However, there was no difference after 3 hours between the two groups. Operative time, intraoperative blood loss, mediastinal blood loss, transfusion requirements, and drainage in the first postoperative 12 hours in the Group A were lower than in Group B, which has significant difference (P<0.05). CONCLUSION: As a result, final ACT values lower than pre-heparinization ACT values are safe and lead to lower operative times, bleeding, and post-operative transfusions.

Visual Acuity Change over 12 Months in the Prospective Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: ProgStar Report Number 6.

PURPOSE: To estimate the yearly rate of change of best-corrected visual acuity (BCVA) and the risk of loss 1 line or more over 1 year and to identify risk factors for BCVA loss in patients with Stargardt disease (STGD1). DESIGN: Multicenter, prospective cohort study. PARTICIPANTS: Two hundred fifty-nine patients (489 eyes) with molecularly confirmed STGD1 enrolled at 9 centers in the United States and Europe. METHODS: Participants were followed up every 6 months, and data at the baseline and 6- and 12-month visits were analyzed. Best-corrected visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Standardized reporting forms were used to collect participants' characteristics and clinical observations. Linear mixed effects models were used to estimate the rate of BCVA loss. Linear models with generalized estimating equations were used to identify risk factors for BCVA loss of 1 line or more over 1 year. MAIN OUTCOME MEASURES: Change in BCVA over 1 year. RESULTS: Cross-sectional analysis at baseline showed that earlier symptom onset and longer duration since onset was associated with worse BCVA. Longitudinal analysis showed no overall significant change of BCVA within 12 months, but the rate of BCVA change was significantly different by baseline BCVA (P < 0.001). The BCVA of eyes with baseline BCVA of 20/25 or better declined at a rate of 2.8 ETDRS letters per year (P = 0.10), eyes with baseline BCVA between 20/25 and 20/70 declined at a rate of 2.3 ETDRS letters per year (P = 0.002), eyes with baseline BCVA between 20/70 and 20/200 declined at a rate of 0.8 ETDRS letters per year (P = 0.08), and eyes with baseline BCVA worse than 20/200 showed a significant improvement of 2.3 ETDRS letters per year (P < 0.001). Overall, 12.9% of eyes lost 1 line or more, and the risk of such BCVA loss was different by baseline BCVA level (P = 0.016). Smoking and vitamin A use was not associated significantly with baseline BCVA, nor with rate of BCVA loss over 1 year. CONCLUSIONS: Change in BCVA in STGD1 patients over a 12-month period was small, but varied depending on baseline BCVA. Given the slow change during 1 year, BCVA is unlikely to be a sensitive outcome measure for STGD1 treatment trials with 1 year's duration.

Trends and Determinants of Human Papillomavirus Concordance Among Human Immunodeficiency Virus-Positive and -Negative Heterosexual Couples in Rakai, Uganda.

Background: Limited data are available on human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-negative or HIV-positive couples followed longitudinally. Methods: Genital HPV was assessed in 725 concordant HIV-negative couples and 209 HIV-positive couples enrolled in a male circumcision trial in Rakai, Uganda, using the Roche Linear Array assay, which detects 37 HPV genotypes. Human papillomavirus prevalence and determinants of genotype-specific concordance were assessed at annual visits. Cumulative detection of HPV genotypes over 2 years was also assessed. Results: At enrollment, HPV infection was detected in 54% of HIV-negative women, 56% of HIV-negative men, and 93% of HIV-positive men and women. For HIV-negative couples, genotypic concordance was 30% at baseline (n = 219/725) and declined significantly with age (adjusted prevelance risk ratio [adjPRR] = 0.53; 95% confidence interval [CI] = 0.28-0.93 comparing women aged >40 years to those aged 15-19 years) and male circumcision (adjPRR = 0.60; 95% CI = 0.47-0.77) and increased among couples with recent intercourse (adjPRR = 1.26; 95% CI = 1.04-1.53). These associations were not seen in HIV-positive couples. Among couples with HPV results at all visits, ≥1 of the same genotypes were detected in both partners in 60% of HIV-negative couples and 96% of HIV-positive couples over 2 years. Conclusion: Human papillomavirus genotype-specific concordance is more common in HIV-positive couples, and irrespective of HIV status, the majority of couples exhibit HPV concordance over 2 years.

Cerebrospinal fluid biomarkers and HIV-associated neurocognitive disorders in HIV-infected individuals in Rakai, Uganda.

In the USA, increased cerebrospinal fluid (CSF) inflammatory cytokines have been observed in antiretroviral therapy (ART)-naive, HIV-seropositive individuals with HIV-associated neurocognitive disorder (HAND). We characterized the relationship between HAND and CSF biomarker expression in ART-naive, HIV-seropositive individuals in Rakai, Uganda. We analyzed CSF of 78 HIV-seropositive, ART-naive Ugandan adults for 17 cytokines and 20 neurodegenerative biomarkers via Luminex multiplex assay. These adults underwent neurocognitive assessment to determine their degree of HAND. We compared biomarker concentrations between high and low CD4 groups and across HAND classifications, adjusting for multiple comparisons. Individuals with CD4 <200 cells/µL (N = 38) had elevated levels of CSF Interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-α, matrix metalloproteinase (MMP)-1, MMP-7, and S100 calcium-binding protein B (S100B) and lower levels of amyloid ß42. Individuals with CD4 351-500 cells/µL (N = 40) had significantly higher CSF levels of interleukin (IL)-1ß, amyloid ß42, and soluble receptor for advanced glycation end products (sRAGE). Increasing levels of S100B, platelet-derived growth factor-AA (PDGF-AA), brain-derived neurotrophic factor (BDNF), and sRAGE were associated with decreased odds of mild neurocognitive disorder (n = 22) or HIV-associated dementia (n = 15) compared with normal function (n = 30) or asymptomatic neurocognitive impairment (n = 11). Increased levels of interferon (IFN)-γ were associated with increased odds of mild neurocognitive impairment or HIV-associated dementia relative to normal or asymptomatic neurocognitive impairment. Proinflammatory CSF cytokines, chemokines, and neurodegenerative biomarkers were present in increasing concentrations with advanced immunosuppression and may play a role in the development of HAND. The presence of select CNS biomarkers may also play a protective role in the development of HAND.

Lymphopenia and its association with survival in patients with locally advanced cervical cancer.

OBJECTIVE: To evaluate the association between lymphopenia and survival in women with cervical cancer treated with primary chemoradiation. METHODS: A single institution, retrospective analysis of patients with stage IB2-IVA cervical cancer who received upfront chemoradiation from 1998 to 2013 was performed. Complete blood counts from pre-treatment to 36 months post-treatment were analyzed. Lymphopenia and known prognostic factors were evaluated for an association with progression-free (PFS) and overall survival (OS). RESULTS: Seventy-one patients met study criteria for whom 47 (66%) had a documented total lymphocyte count (TLC) two months after initiating chemoradiation. FIGO stage distribution was 6% Stage I, 46% Stage II, 45% Stage III and 3% Stage IV. Pre-treatment TLC was abnormal (<1000 cells/mm3) in 15% of patients. The mean reduction in TLC was 70% two months after initiating chemoradiation. Severe post-treatment lymphopenia (TLC <500 cells/mm3) was observed in 53% of patients; they experienced inferior median OS (21.2 vs. 45.0 months, P=0.03) and similar 25th percentile PFS (6.3 vs. 7.7 months, P=0.06) compared to patients without severe lymphopenia. Multivariate analysis demonstrated pre-treatment TLC ≥1000 cells/mm3 and post-treatment TLC >500 cells/mm3 had a 77% (HR: 0.23; 95% CI 0.05-1.03; P=0.053) and 58% decrease in hazards of death (HR: 0.42; 95%CI 0.12-1.46; P=0.17) respectively. CONCLUSION: More than half of cervical cancer patients treated with chemoradiation experienced severe and prolonged lymphopenia. Although statistical significance was not reached, the findings suggest that pre- and post-treatment lymphopenia may be associated with decreased survival. Further research is warranted, given that lymphopenia could be a reversible prognostic factor.