Longitudinal cognitive evaluation before and after delivery among people with preeclampsia.

BACKGROUND: Cognitive impairments related to preeclampsia after pregnancy have been reported; however, it is not known if weaknesses in cognition occur before and shortly after delivery. OBJECTIVE: This study aimed to assess the feasibility of longitudinal cognitive testing before and after delivery, and to investigate whether those with preeclampsia have cognitive weaknesses during the third trimester of pregnancy and at 1 and 3 months postpartum. We hypothesized that people with preeclampsia would have lower cognition scores across all time points compared with normotensive people. STUDY DESIGN: This longitudinal, prospective, observational study in a single institution enrolled people (N=30) at ≥28 weeks of gestation with preeclampsia (N=16) or normotension (N=14). People with chronic hypertension, neurologic or developmental disabilities, moderate or severe depression or anxiety, or current substance use were excluded. Subjective (Everyday Cognition Scale) and objective assessment of executive function (Stroop Color-Word Interference Test, Trail-Making Test), attention and working memory (Digit Span subtest), and information processing speed (Digit Symbol Substitution Test) was conducted, and Z-scores were calculated. Baseline characteristics (eg, prepregnancy body mass index) were collected from the medical record. Generalized linear models were used to estimate associations. RESULTS: We enrolled 37% (30/81) of eligible people and retained 80% (24/30) and 53% (16/30) at 1 and 3 months postpartum, respectively. People with preeclampsia reported more memory problems (ß=0.87; 95% confidence interval, 0.44-1.31), and scored worse on attention and working memory (ß=-0.94; 95% confidence interval, -1.42 to -0.45) and executive function (Stroop test ß=-0.86; 95% confidence interval, -1.53 to -0.19) domains compared with normotensive people after adjusting for time, age, education, and prepregnancy body mass index. CONCLUSION: Longitudinal assessment of cognition in pregnant preeclamptic and normotensive people is feasible. People with preeclampsia reported worse subjective memory and had lower scores in attention, working memory, and executive function.

SARS-CoV-2 control on a large urban college campus without mass testing.

OBJECTIVE: A small percentage of universities and colleges conducted mass SARS-CoV-2 testing. However, universal testing is resource-intensive, strains national testing capacity, and false negative tests can encourage unsafe behaviors. PARTICIPANTS: A large urban university campus. METHODS: Virus control centered on three pillars: mitigation, containment, and communication, with testing of symptomatic and a random subset of asymptomatic students. RESULTS: Random surveillance testing demonstrated a prevalence among asymptomatic students of 0.4% throughout the term. There were two surges in cases that were contained by enhanced mitigation and communication combined with targeted testing. Cumulative cases totaled 445 for the term, most resulting from unsafe undergraduate student behavior and among students living off-campus. A case rate of 232/10,000 undergraduates equaled or surpassed several peer institutions that conducted mass testing. CONCLUSIONS: An emphasis on behavioral mitigation and communication can control virus transmission on a large urban campus combined with a limited and targeted testing strategy.

MRI as First Line Imaging for Suspected Acute Appendicitis during Pregnancy: Diagnostic Accuracy and level of Inter-Radiologist Agreement.

OBJECTIVE: Evaluation of acute appendicitis (AA) in pregnancy is supported with diagnostic imaging. Typically, ultrasound (US) is performed first, and then often followed by magnetic resonance imaging (MRI) due to continued diagnostic uncertainty. The purpose of our study was to evaluate the sensitivity, specificity, and accuracy of US as compared to MRI and to evaluate the inter-radiologist agreement amongst body Radiologists with varying levels of expertise. MATERIALS AND METHODS: We performed a retrospective study of 364 consecutive pregnant patients with clinical suspicion of AA at a single center over a 6-year period. Sensitivity, Specificity, accuracy, positive and negative predictive values were calculated for US and MRI. Inter Radiologist agreement was determined using Cohen's Kappa analysis between original interpreting Radiologist and retrospective review by expert Radiologist. RESULTS: Thirty-one of 364 patients (8.5%) underwent appendectomy based on preoperative diagnosis, with confirmation of acute appendicitis (AA) by pathology in 19. US was able to visualize the appendix in only 6 (1.65%), 5 of whom had appendicitis. 141 patients underwent MRI, and correctly diagnosed appendicitis in 9. No patient with a negative MRI diagnosis had AA. The sensitivity, and negative predictive value for diagnosing AA with MRI was 100%. The MRI inter-reader agreement for appendix visualization and overall accuracy were 87.9 and 98% with Cohen Kappa of 0.7 and 0.56 respectively. CONCLUSIONS: Our data suggests that MRI should be considered the first line imaging modality in pregnant patients suspected of having AA. Body Radiologists with varied levels of experience in MRI readouts had substantial agreement.

Using capture-recapture methods to estimate influenza hospitalization incidence rates.

BACKGROUND: Accurate population estimates of disease incidence and burden are needed to set appropriate public health policy. The capture-recapture (C-R) method combines data from multiple sources to provide better estimates than is possible using single sources. METHODS: Data were derived from clinical virology test results and from an influenza vaccine effectiveness study from seasons 2016-2017 to 2018-2019. The Petersen C-R method was used to estimate the population size of influenza cases; these estimates were then used to calculate adult influenza hospitalization burden using a Centers for Disease Control and Prevention (CDC) multiplier method. RESULTS: Over all seasons, 343 influenza cases were reported in the clinical database, and 313 in the research database. Fifty-nine cases (17%) reported in the clinical database were not captured in the research database, and 29 (9%) cases in the research database were not captured in the clinical database. Influenza hospitalizations were higher among vaccinated (58%) than the unvaccinated (35%) in the current season and were similar among unvaccinated (51%) and vaccinated (49%) in the previous year. Completeness of the influenza hospitalization capture was estimated to be 76%. The incidence rates for influenza hospitalizations varied by age and season and averaged 307-309 cases/100,000 adult population annually. CONCLUSION: Using C-R methods with more than one database, along with a multiplier method with adjustments improves the population estimates of influenza disease burden compared with relying on a single-data source.

Clinical outcomes following selective laser trabeculoplasty in Afro-Caribbean patients with glaucoma at high risk for progression.

AIM: To characterise clinical outcomes following selective laser trabeculoplasty (SLT) in eyes of Afro-Caribbean patients with open-angle glaucoma (OAG) at high risk for progression. METHODS: In a prospective interventional case series, patients meeting high-risk criteria (advanced disease, unilateral glaucoma blindness, inadequate intraocular pressure (IOP) on >2 medications, recent progression on medications, inability to administer, afford or tolerate medications) underwent bilateral 360° SLT and managed based on their subsequent clinical course. Patient-specific indications for SLT-IOP reduction (IOP group) or reduced reliance on medical therapy (MED group)-were recorded before treatment. IOP and medication use were recorded every 3-4 months through up to 24 months of follow-up. Outcomes were analysed separately in the IOP and MED groups. RESULTS: Among 33 right eyes (left eye outcomes were similar) in the IOP group, mean (SD) IOP was significantly reduced from 21.7 (7.5) mm Hg to 16.2-17.1 mm Hg over follow-up (p<0.0177); medication use remained unchanged (p>0.05) at all time points. Among 36 right eyes in the MED group, mean medication use was 1.9 (0.9) at baseline and ranged from 1.2 to 1.4 medications per eye through follow-up (p<0.0033), and mean IOP was significantly reduced at months 1-6 (to 13.1 (2.3) mm Hg, p=0.0013), months 13-18 (to 14.3 (2.8), p=0.0136) and unchanged at other time points. No vision-threatening adverse events occurred. CONCLUSIONS: Afro-Caribbean patients with OAG at risk for progression can achieve clinically and statistically significant reductions in IOP or medications through up to 24 months following a single 360° SLT treatment. TRIAL REGISTRATION NUMBER: NCT02375009.

Role of Age in the Spread of Influenza, 2011-2019: Data From the US Influenza Vaccine Effectiveness Network.

Intraseason timing of influenza infection among persons of different ages could reflect relative contributions to propagation of seasonal epidemics and has not been examined among ambulatory patients. Using data from the US Influenza Vaccine Effectiveness Network, we calculated risk ratios derived from comparing weekly numbers of influenza cases prepeak with those postpeak during the 2010-2011 through 2018-2019 influenza seasons. We sought to determine age-specific differences during the ascent versus descent of an influenza season by influenza virus type and subtype. We estimated 95% credible intervals around the risk ratios using Bayesian joint posterior sampling of weekly cases. Our population consisted of ambulatory patients with laboratory-confirmed influenza who enrolled in an influenza vaccine effectiveness study at 5 US sites during 9 influenza seasons after the 2009 influenza A virus subtype H1N1 (H1N1) pandemic. We observed that young children aged <5 years tended to more often be infected with H1N1 during the prepeak period, while adults aged ≥65 years tended to more often be infected with H1N1 during the postpeak period. However, for influenza A virus subtype H3N2, children aged <5 years were more often infected during the postpeak period. These results may reflect a contribution of different age groups to seasonal spread, which may differ by influenza virus type and subtype.

Risk Factors Associated with Adnexal Torsion after Hysterectomy.

STUDY OBJECTIVE: To identify preoperative and intraoperative risk factors for adnexal torsion after hysterectomy, and to estimate the incidence of the disease in the modern-day era of laparoscopic surgery. DESIGN: Retrospective nested case-control study. SETTING: Large urban medical system. PATIENTS: Eighty-nine female patients ages 17 to 51. INTERVENTIONS: Patients underwent ovarian-sparing hysterectomy. MEASUREMENTS AND MAIN RESULTS: The estimated incidence of ovarian torsion after hysterectomy was 0.5% (46/8538 ovarian-sparing hysterectomies). The following variables were found to be associated with adnexal torsion after hysterectomy in an adjusted logistic regression: laparoscopic or laparoscopic-assisted approach to hysterectomy vs any other approach (odds ratio [OR], 3.36; 95% confidence interval [CI], 0.86-13.23); younger age at the time of hysterectomy (17-40 years) vs older age (41-51 years) (OR, 3.45; 95% CI, 1.33-8.97); and a gynecologic history significant for endometriosis (OR, 4.07; 95% CI, 1.04-15.88). CONCLUSION: There is an association between laparoscopic approach to hysterectomy, younger age at time of hysterectomy, and a history of endometriosis with subsequent risk of adnexal torsion. Providers should have a heightened index of suspicion for adnexal torsion after hysterectomy in patients presenting with acute-onset abdominal pain who underwent laparoscopic hysterectomy at a younger age.

Messenger RNA Vaccine Effectiveness Against Coronavirus Disease 2019 Among Symptomatic Outpatients Aged ≥16 Years in the United States, February-May 2021.

Evaluations of vaccine effectiveness (VE) are important to monitor as coronavirus disease 2019 (COVID-19) vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, the VE of messenger RNA vaccines against COVID-19 was 91% (95% confidence interval, 83%-95%) for full vaccination and 75% (55%-87%) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.

Long-Term Outcomes of Selective Laser Trabeculoplasty for Open-Angle Glaucoma in the Caribbean.

PURPOSE: To characterize long-term clinical outcomes of monotherapy selective laser trabeculoplasty (SLT) in Afro-Caribbean patients with open-angle glaucoma (OAG). DESIGN: This was a post hoc analysis of nearly 8 years (median, 3.2; interquartile range, 2.1-7.1) of pooled data from the West Indies Glaucoma Laser Study and its preliminary study. METHODS: Setting: Three eye care practices in Saint Lucia and Dominica. PARTICIPANTS: Afro-Caribbean adults with mild-moderate OAG treated with ≤2 medications (61 in preliminary study, 72 in West Indies Glaucoma Laser Study). INTERVENTION: Participants underwent medication washout, baseline intraocular pressure (IOP) determination, and bilateral 360-degree SLT. Participants were followed for up to 94 months. Repeat SLT was performed according to prespecified criteria. MAIN OUTCOME MEASURES: The primary outcome was mean IOP reduction from baseline. The secondary outcome was medication-free survival with SLT repeated as needed. RESULTS: The pooled data set included 265 eyes of 133 Afro-Caribbean participants. The mean (standard deviation) baseline IOP was 21.2 (3.4) and 21.2 (3.9) mmHg in right and left eyes, respectively. Over 8 years, the mean IOP ranged from 12.8 to 15.7 mm Hg and from 13.1 to 15.8 mm Hg, respectively (P < .0001 for every comparison with baseline). The median medication-free survival time for initial SLT was 85.4 months in both eyes. The 94-month medication-free survival of SLT repeated as needed was 71.2% and 71.7%, respectively. CONCLUSIONS: Monotherapy SLT, repeated as needed, safely provides significant IOP reductions in most Afro-Caribbean adults with primary OAG through nearly 8 years of follow-up and has significant potential to delay or prevent glaucoma-related vision loss in black patients in low-resource regions.

Assessing the Reliability of Intraocular Pressure Measurements Using Rebound Tonometry.

PRECIS: In a trio of prospective studies, the iCare rebound tonometer demonstrated significantly lower test-retest variability than Goldmann tonometry with good interoperator and interdevice reproducibility, supporting its value in monitoring intraocular pressure (IOP) changes over time. PURPOSE: The purpose of this study was to characterize intraoperator and interoperator and interdevice reliability of IOP measurements with rebound tonometry (RT, ic100). METHODS: Three prospective cross-sectional studies were conducted in distinct sample of adult patients with established glaucoma, suspected glaucoma, or no glaucoma at the West Virginia University Eye Institute. Participants in study 1 underwent 5 RT measurements in one randomly selected eye and 5 Goldmann tonometry measurements in the fellow eye by 1 operator; intraoperator variability was compared using the F test. In study 2, 3 operators each obtained 3 RT measurements in participants in randomized operator order. In study 3, a single operator collected 3 measurements each with 3 RTs in randomized device order. Between-operator and between-device reproducibility were characterized using intraclass correlation coefficients (ICCs). RESULTS: Overall, 28, 19, and 25 subjects participated in the 3 respective studies. Within-subject variance across subjects was 0.757 in RT measurements and 2.471 in Goldmann measurements (P=0.0035). Interoperator reproducibility of RT measurements was good in both eyes [ICC for right eyes 0.78, 95% confidence interval (CI): 0.60-0.85; ICC for left eyes 0.75, 95% CI: 0.50-0.83]. Interdevice reproducibility of RT measurements was good approaching excellent (ICC for right eyes 0.87, 95% CI: 0.83-0.90; ICC for left eyes 0.89, 95% CI: 0.86-0.91). CONCLUSIONS: The RT's lower measurement variability and good interoperator and interdevice reproducibility suggest that it can characterize IOP changes over time more robustly than Goldmann tonometry, aiding clinicians in assessing the effectiveness of glaucoma therapy and the consistency of IOP control.

Claudin-1 down-regulation in the prostate is associated with aging and increased infiltration of inflammatory cells in BPH.

INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is an age-related disease that is frequently associated with chronic prostatic inflammation. In previous studies, we detected the presence of PSA protein in the stroma of BPH nodules and down-regulation of junction proteins E-cadherin and claudin-1. Transmission electron microscopy (TEM) imaging showed a decrease in tight junctions suggesting the luminal epithelial barrier in BPH tissues may be compromised. Recent in vitro studies showed that stimulation of benign prostate epithelial cell lines with TGF-ß1 induced a decrease in claudin-1 expression suggesting that inflammation might be associated with alterations in the prostate epithelial barrier. This study explored the potential associations between aging and loss of junction proteins and the presence of inflammatory cells in prostate tissue specimens from young healthy donors and aged BPH patients. METHODS: Immunostaining of serial prostate sections from 13 BPH patients and five healthy young donors was performed for claudin-1, CD4, CD8, CD20 and CD68. H-Scores and the number of inflammatory cells were calculated for the same area in donor, normal adjacent prostate (NAP) to and BPH specimens. Quantification and statistical correlation analyses were performed. RESULTS: Claudin-1 immunostaining was inversely associated with increasing age, and inflammation in prostate specimens. B-cell infiltration increased with age and BPH was associated with an increased infiltration of T-cells and macrophages compared to NAP. CONCLUSIONS: These findings suggest that aging is associated with down-regulation of claudin-1 and claudin-1 is further decreased in BPH. Claudin-1 down-regulation was associated with increased infiltration of inflammatory cells in both NAP and BPH tissues. Claudin-1 down-regulation in the aging prostate could contribute to increased prostatic inflammation, subsequently contributing to BPH pathogenesis.

E-cadherin expression is inversely correlated with aging and inflammation in the prostate.

INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is a prostatic disease that is significantly associated with aging. However, it is not well understood how aging contributes to BPH pathogenesis. Several factors associated with an increased risk of BPH are also associated with increasing age, including chronic inflammation and declining epithelial barrier function. Thus, this study explored the potential associations between aging, loss of adherens junction protein E-cadherin and the presence of inflammatory mediators in prostate tissue specimens from healthy young donor and BPH patients. METHODS: Serial prostate sections from a cohort of five donors aged 15-26 years and 13 BPH patients aged 50-77 years were immunostained with E-cadherin, COX-2, CD4, CD8, CD20 and CD68. E-cadherin and COX-2 H-Scores and the number of inflammatory cells were calculated for the same area in donor, normal adjacent prostate to BPH (NAP) and BPH specimens. Quantification and statistical correlation analyses were performed for comparisons between groups. RESULTS: E-cadherin was decreased in aged NAP tissues and in BPH compared to young donor tissue. E-cadherin was inversely correlated with age and infiltration of inflammatory cells in NAP compared to young healthy donor prostate. Stromal COX-2 was positively correlated with age and inflammation. E-cadherin was further down-regulated in BPH, while COX-2 H-Scores were not significantly altered in BPH compared to NAP. CONCLUSIONS: These findings suggest that aging is associated with down-regulation of E-cadherin and up-regulation of stromal COX-2 immunostaining in the prostate. E-cadherin immunostaining was inversely associated with age and inflammation, while stromal COX-2 immunostaining was positively associated with age and inflammation in the prostate. These findings suggest that the prostate epithelial barrier is altered and inflammation is increased with age in the prostate. These changes are further exacerbated in BPH, and may be involved in BPH pathogenesis.

Effectiveness of Influenza Vaccine for Preventing Laboratory-Confirmed Influenza Hospitalizations in Immunocompromised Adults.

BACKGROUND: Yearly influenza immunization is recommended for immunocompromised (IC) individuals, although immune responses are lower than that for the nonimmunocompromised and the data on vaccine effectiveness (VE) in the IC is scarce. We evaluated VE against influenza-associated hospitalization among IC adults. METHODS: We analyzed data from adults ≥ 18 years hospitalized with acute respiratory illness (ARI) during the 2017-2018 influenza season at 10 hospitals in the United States. IC adults were identified using prespecified case definitions using electronic medical record data. VE was evaluated with a test-negative case-control design using multivariable logistic regression with polymerase chain reaction-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, enrolling site, illness onset date, race, days from onset to specimen collection, self-reported health, and self-reported hospitalizations. RESULTS: Of 3524 adults hospitalized with ARI, 1210 (34.3%) had an immunocompromising condition. IC adults were more likely to be vaccinated than non-IC (69.5% vs 65.2%) and less likely to have influenza (22% vs 27.8%). The mean age did not differ among IC and non-IC (61.4 vs 60.8 years of age). The overall VE against influenza hospitalization, including immunocompetent adults, was 33% (95% confidence interval [CI], 21-44). VE among IC vs non-IC adults was lower at 5% (95% CI, -29% to 31%) vs 41% (95% CI, 27-52) (P < .05 for interaction term). CONCLUSIONS: VE in 1 influenza season was very low among IC individuals. Future efforts should include evaluation of VE among the different immunocompromising conditions and whether enhanced vaccines improve the suboptimal effectiveness among the immunocompromised.

Treatment selection and survival outcomes in Early-Stage peripheral T-Cell lymphomas: does anaplastic lymphoma kinase mutation impact the benefit of consolidative radiotherapy?

The role of consolidative radiotherapy (RT) is less substantiated in uncommon peripheral T-cell lymphomas (PTCLs). Anaplastic lymphoma kinase (ALK) mutation sub-categorizes PTCLs, with ALK (+) having a distinctly favorable prognosis. We aimed to use the National Cancer Database to examine the potential role of RT in PTCLs and if ALK mutation can be used to predict the benefit of consolidative RT after multi-agent chemotherapy (combined modality therapy). We identified 3670 stage I-II PTCL patients treated with multi-agent chemotherapy alone or combined modality therapy (CMT) between 1998-2012. After adjusting for immortal-time and indication bias, CMT was associated with better OS than multi-agent chemotherapy alone for ALK (-) patients (HR 0.69, 95% CI 0.52-0.92, p = .01); no significant difference was noted for ALK (+) (HR 1.03, 95% CI 0.75-1.41, p = .85). CMT is associated with improved OS for ALK (-) PTCLs; while no such benefit was seen for the ALK (+) subgroup.

Corneal Endothelial Cell Changes After Phacoemulsification Combined with Excisional Goniotomy with the Kahook Dual Blade or iStent: A Prospective Fellow-Eye Comparison.

PURPOSE: To characterize changes in endothelial cell density and morphology following phacoemulsification combined with either excisional goniotomy with the Kahook Dual Blade (KDB-phaco) or first-generation iStent trabecular microbypass implantation (iStent-phaco). SETTING: A single clinical practice. METHODS: Twenty-one adult subjects from one center with visually significant cataract and mild-moderate open-angle glaucoma underwent KDB-phaco or iStent-phaco in one eye and the alternate procedure in the fellow eye as part of a prospective, multicenter, randomized trial. Specular microscopy and pachymetry were performed before and 6-29 months after surgery. Parameters analyzed included change from baseline of endothelial cell density (ECD), the coefficient of variation (CV), the percent of hexagonal cells (%HEX), and central corneal thickness (CCT). RESULTS: Baseline ECD, CV, %HEX, and CCT were similar between groups. A mean (standard deviation) of 18.2 (5.8) months postoperatively (range 12.5-28.7 months), the change from baseline in ECD was -90 ± 226 cells/mm2 (-3.4%) in KDB-phaco eyes (p=0.083) and -239 ± 247 cells/mm2 (-9.0%) in iStent-phaco eyes (p<0.001); the change in iStent-phaco eyes was significantly greater than in KDB-phaco eyes (p=0.013). The magnitude of Endothelial Cell Loss (ECL) was not correlated with length of postoperative follow-up time in either group. No significant differences in change from baseline in CV, %HEX, or CCT were noted with the exception of a decrease in %HEX in iStent-phaco eyes (p=0.017). No eyes manifested corneal edema, decompensation, or other cornea-related complications. CONCLUSION: Both KDB-phaco and iStent-phaco are associated with postoperative ECL, with iStent-phaco producing significantly greater ECL than KDB-phaco. The clinical significance of these findings is unclear, and future studies are warranted to more robustly characterize long-term effects of glaucoma surgical procedures-with and without permanent implants-on ECD and corneal health and to develop evidence-based guidelines for the pre- and post-operative evaluation of corneal health in eyes undergoing glaucoma surgery.

Two-Year Clinical Outcomes of Combined Phacoemulsification, Goniosynechialysis, and Excisional Goniotomy For Angle-Closure Glaucoma.

PURPOSE: The aim of this study was to describe changes in intraocular pressure (IOP) and IOP medications after phacoemulsification with Kahook Dual Blade-assisted goniosynechialysis and excisional goniotomy in eyes with angle-closure glaucoma and cataract. DESIGN: Retrospective case series. METHODS: Data were collected retrospectively through 24 months of follow-up in 42 eyes of 24 subjects. RESULTS: Preoperative mean (SE) IOP was 25.5 (0.7) mm Hg using a mean of 2.3 (0.1) medications per eye. At month 24, mean IOP had decreased to 13.5 (0.4) mm Hg [a reduction of 12.0 mm Hg (47.1%); P < 0.0001]. Medication use declined to a mean of 0.6 (0.2) medications per eye [a reduction of 1.7 medications per eye (76%); P < 0.0001]. At month 24, 40 of 42 eyes (95.2%) achieved IOP ≤18 mm Hg, 42 of 42 eyes (100%) achieved IOP reduction of ≥20%, 36 of 42 eyes (85.7%) required ≥1 fewer medications for IOP control, and 29 of 42 (69.0%) were medication-free. No eyes required additional glaucoma surgery throughout 24 months of follow-up. CONCLUSIONS: Phaco plus Kahook Dual Blade-assisted goniosynechialysis/excisional goniotomy provides statistically and clinically meaningful reductions in both IOP and medications in eyes with angle-closure glaucoma throughout 2 years of follow-up. These findings are consistent with our previously reported outcomes in this cohort at months 6 and 12 postoperatively, demonstrating a significant and sustained benefit of this procedure in eyes with angle-closure glaucoma and cataract.

Tight junction protein claudin-1 is downregulated by TGF-ß1 via MEK signaling in benign prostatic epithelial cells.

BACKGROUND: Benign prostatic hyperplasia (BPH) is arguably the most common disease in aging men. Although the etiology is not well understood, chronic prostatic inflammation is thought to play an important role in BPH initiation and progression. Our recent studies suggest that the prostatic epithelial barrier is compromised in glandular BPH tissues. The proinflammatory cytokine transforming growth factor beta 1 (TGF-ß1) impacts tight junction formation, enhances epithelial barrier permeability, and suppresses claudin-1 messenger RNA expression in prostatic epithelial cells. However, the role of claudin-1 in the prostatic epithelial barrier and its regulation by TGF-ß1 in prostatic epithelial cells are not clear. METHODS: The expression of claudin-1 was analyzed in 22 clinical BPH specimens by immunohistochemistry. Human benign prostate epithelial cell lines BPH-1 and BHPrE1 were treated with TGF-ß1 and transfected with small interfering RNAs specific to claudin-1. Epithelial monolayer permeability changes in the treated cells were measured using trans-epithelial electrical resistance (TEER). The expression of claudin-1, E-cadherin, N-cadherin, snail, slug, and activation of mitogen-activated proteins kinases (MAPKs) and AKT was assessed following TGF-ß1 treatment using Western blot analysis. RESULTS: Claudin-1 expression was decreased in glandular BPH tissue compared with adjacent normal prostatic tissue in patient specimens. TGF-ß1 treatment or claudin-1 knockdown in prostatic epithelial cell lines increased monolayer permeability. TGF-ß1 decreased levels of claudin-1 and increased levels of snail and slug as well as increased phosphorylation of the MAPK extracellular signal-regulated kinase-1/2 (ERK-1/2) in both BPH-1 and BHPrE1 cells. Overexpression of snail or slug had no effect on claudin-1 expression. In contrast, PD98059 and U0126, inhibitors of the upstream activator of ERK-1/2 (ie, MEK-1/2) restored claudin-1 expression level as well as the epithelial barrier. CONCLUSION: Our findings suggest that downregulation of claudin-1 by TGF-ß1 acting through the noncanonical MEK-1/2/ERK-1/2 pathway triggers increased prostatic epithelial monolayer permeability in vitro. These findings also suggest that elevated TGF-ß1 may contribute to claudin-1 downregulation and compromised epithelial barrier in clinical BPH specimens.

Proposed Clinical Indicators for Efficient Screening and Testing for COVID-19 Infection from Classification and Regression Trees (CART) Analysis.

BACKGROUND: The introduction and rapid transmission of SARS CoV2 in the United States resulted in implementation of methods to assess, mitigate and contain the resulting COVID-19 disease based on limited knowledge. Screening for testing has been based on symptoms typically observed in inpatients, yet outpatient symptom complexes may differ. METHODS: Classification and regression trees (CART) recursive partitioning created a decision tree classifying enrollees into laboratory-confirmed cases and non-cases. Demographic and symptom data from patients ages 18-87 years who were enrolled from March 29-April 26, 2020 were included. Presence or absence of SARSCoV2 was the target variable. RESULTS: Of 736 tested, 55 were positive for SARS-CoV2. Cases significantly more often reported chills, loss of taste/smell, diarrhea, fever, nausea/vomiting and contact with a COVID-19 case, but less frequently reported shortness of breath and sore throat. A 7-terminal node tree with a sensitivity of 96% and specificity of 53%, and an AUC of 78% was developed. The positive predictive value for this tree was 14% while the negative predictive value was 99%. Almost half (44%) of the participants could be ruled out as likely non-cases without testing. DISCUSSION: Among those referred for testing, negative responses to three questions could classify about half of tested persons with low risk for SARS-CoV2 and would save limited testing resources. These questions are: was the patient in contact with a COVID-19 case? Has the patient experienced 1) a loss of taste or smell; or 2) nausea or vomiting? The outpatient symptoms of COVID-19 appear to be broader than the well-known inpatient syndrome.

Excisional goniotomy vs trabecular microbypass stent implantation: a prospective randomized clinical trial in eyes with mild to moderate open-angle glaucoma.

PURPOSE: To compare reduction in intraocular pressure (IOP) and IOP-lowering medication in eyes undergoing excisional goniotomy with Kahook Dual Blade (KDB) vs iStent microbypass implantation, both combined with phacoemulsification, in eyes with mild to moderate open-angle glaucoma (OAG). SETTING: Nine practices in the United States. DESIGN: Prospective, randomized, active-controlled, parallel-group clinical trial. METHODS: Eyes were randomized to KDB-Phaco or iStent-Phaco group. Demographics, corrected distance visual acuity, IOP, IOP-lowering medications, and adverse events were collected at baseline and at day 1, week 1, and months 1, 3, 6, and 12 postoperatively. The primary outcome measure was the proportion of eyes at 12 months with IOP reduction of 20% or greater or IOP medication reduction of 1 or more compared with baseline. RESULTS: For this study, 164 eyes of 164 patients were analyzed (82 in each group). Mean IOP was reduced at 12 months compared with baseline from 18.5 (standard of error 0.4) to 15.4 (0.4) mm Hg in the KDB-Phaco group and from 18.5 (0.3) to 16.1 (0.4) mm Hg in the iStent-Phaco group (P = .24). Mean IOP-lowering medications were reduced from 1.3 (0.1) to 0.3 (0.1) in the KDB-Phaco group and from 1.4 (0.1) to 0.4 (0.1) in the iStent-Phaco group (P = .17). Among study completers, the primary outcome was attained in 74 (93.7%) of 79 patients of KDB-Phaco eyes and 65 (83.3%) of 78 patients of iStent-Phaco eyes (P = .04). Both procedures had similar safety profiles. CONCLUSIONS: Both procedures lowered both IOP and the need for IOP-lowering medications effectively and safely in eyes with mild to moderate OAG and cataract. Significantly, more KDB-Phaco eyes than iStent-Phaco eyes met the primary outcome of 20% or greater IOP reduction or 1 or more medication reduction at 12 months.

Influenza vaccine effectiveness among outpatients in the US Influenza Vaccine Effectiveness Network by study site 2011-2016.

BACKGROUND: Influenza vaccination is recommended for all US residents aged ≥6 months. Vaccine effectiveness (VE) varies by age, circulating influenza strains, and the presence of high-risk medical conditions. We examined site-specific VE in the US Influenza VE Network, which evaluates annual influenza VE at ambulatory clinics in geographically diverse sites. METHODS: Analyses were conducted on 27 180 outpatients ≥6 months old presenting with an acute respiratory infection (ARI) with cough of ≤7-day duration during the 2011-2016 influenza seasons. A test-negative design was used with vaccination status defined as receipt of ≥1 dose of any influenza vaccine according to medical records, registries, and/or self-report. Influenza infection was determined by reverse-transcription polymerase chain reaction. VE estimates were calculated using odds ratios from multivariable logistic regression models adjusted for age, sex, race/ethnicity, time from illness onset to enrollment, high-risk conditions, calendar time, and vaccination status-site interaction. RESULTS: For all sites combined, VE was statistically significant every season against all influenza and against the predominant circulating strains (VE = 19%-50%) Few differences among four sites in the US Flu VE Network were evident in five seasons. However, in 2015-16, overall VE in one site was 24% (95% CI = -4%-44%), while VE in two other sites was significantly higher (61%, 95% CI = 49%-71%; P = .002, and 53%, 95% CI = 33,67; P = .034). CONCLUSION: With few exceptions, site-specific VE estimates aligned with each other and overall VE estimates. Observed VE may reflect inherent differences in community characteristics of the sites and highlights the importance of diverse settings for studying influenza vaccine effectiveness.