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Chronic pain is a significant public health problem and is exacerbated by stress. The World Trade Center (WTC) Disaster represents a unique stressor, and responders to the WTC disaster are at increased risk for pain and other health complaints. Therefore, there is a significant need to identify vulnerability factors for exacerbated pain experience among this high-risk population. Anxiety sensitivity (AS), defined as fear of anxiety-related sensations, is one such vulnerability factor associated with pain intensity and disability. Yet, no work has tested the predictive effects of AS on pain, limiting conclusions regarding the predictive utility and direction of associations. Therefore, the current study examined the prospective associations of AS, pain intensity, and pain interference among 452 (M

PURPOSE: To evaluate postoperative subjective quality of vision in patients who underwent Implantable Collamer Lens (ICL) (STAAR Surgical) implantation for correction of myopia and to identify potential predictive parameters. METHODS: In this single-center cross-sectional study, a total of 162 eyes of 81 patients (58 women, 23 men) who underwent ICL implantation were analyzed. The Quality of Vision (QOV) questionnaire was used to assess patient-reported outcomes. Baseline characteristics (eg, age), treatment parameters (eg, surgical corrected refraction), and refractive (eg, residual refraction) and visual (eg, uncorrected distance visual acuity) outcomes were analyzed regarding their effect on QOV. RESULTS: Mean age was 33.3 ± 7.0 years (range: 21 to 51 years) and mean preoperative spherical equivalent was −8.42 ± 2.49 diopters (D) (range: −3.25 to −14.38 D). After a mean postoperative follow-up period of 19 ± 14 months (range: 6 to 54 months), the safety index score was 1.23 ± 0.21 and the efficacy index score was 1.17 ± 0.22. The mean QOV scores were 35.5 ± 11.3, 32.2 ± 11.1, and 23.3 ± 16.1 for frequency, severity, and bothersomeness, respectively. The most frequently experienced symptoms were halos (90.1%) and glare (66.7%). Halos appeared in 66.7% of the patients “occasionally” and 5 of them (6.2%) experienced them “very often.” Only 1 patient (1.2%) classified halos as “very bothersome.” Patients older than 36 years reported visual symptoms more frequently ( P < .05) and showed higher bothersomeness scores ( P = .01). CONCLUSIONS: Halos are the most commonly perceived long-term visual disturbance after myopic ICL implantation with a central hole. Visual symptoms can persist more than 6 months postoperatively, causing only minor disturbances in most cases. Older patients seem more prone to experiencing these symptoms. [ J Refract Surg . 2022;38(5):280–287.]

Luft is professor emerita, School of Lifespan Development and Educational Sciences, College of Education, Health and Human Services, Kent State University, Kent, OH. She was president of the Council on Education of the Deaf (CED) from 2018 to 2020. Fischgrund is adjunct faculty, Department of Special Education, Saint Joseph's University, Philadelphia, PA. He was CED executive director from 2012 to 2019. Eardley is the owner of Future Endeavors Consulting, Cleveland, OH. Tanner is a teacher of deaf and hard of hearing students, Pasco County (FL) Schools. Reusser is a staff interpreter, Cleveland Hearing and Speech Center. Eardley, Tanner, and Reusser were graduate assistants at Kent State University when the research for the present article was conducted.Teacher shortages and alternative licensure requirements, in combination with inconsistent state licensure regulations, suggest that not all teachers of deaf and hard of hearing students have the expertise to successfully educate their students. Most national, regional, and specialized professional accreditations do not assess DHH-specific instructional and communication proficiencies, and thus may contribute to DHH students' low achievement levels relative to those of their hearing peers. The study surveyed teaching licensure requirements across the 50 states and District of Columbia regarding compliance with federal requirements and state variations. Results showed that 39% of states did not require a DHH-specific teacher-training program; 45% did not employ a DHH-specific licensure exam. Only 25% required documentation of language/communication skills. A specialized accrediting organization, such as the Council on Education of the Deaf, could help identify well-prepared teachers to fill current and future vacancies and thereby improve DHH students' achievement.

Allogeneic haematopoietic-cell transplantation (allo-HCT) is a potentially curative therapy for high-risk myelodysplastic syndrome (MDS). Reduced-intensity conditioning (RIC) is usually associated with lower non-relapse mortality (NRM), higher relapse rate and similar overall-survival (OS) as myeloablative-conditioning (MAC). Fludarabine/treosulfan (FT) is a reduced-toxicity regimen with intense anti-leukaemia activity and a favourable toxicity profile. We investigated post-transplant outcomes in 1722 MDS patients following allo-HCT with FT (n=367), RIC (n=687) or MAC (n=668). FT and RIC recipients were older than MAC recipients, median age 59, 59 and 51years, respectively (P&nbsp

Background The World Trade Center (WTC) general responder cohort (GRC) was exposed to environmental toxins possibly associated with increased risk of developing autoimmune conditions. Objectives Two study designs were used to assess incidence and risks of autoimmune conditions in the GRC. Methods Three clinically trained professionals established the status of possible GRC cases of autoimmune disorders adhering to diagnostic criteria, supplemented, as needed, by specialists' review of consenting responders' medical records. Nested case-control analyses using conditional logistic regression estimated the risk associated with high WTC exposure (being in the 9/11/2001 dust cloud or ≥median days' response worked) compared with low WTC exposure (all other GRC members'). Four controls were matched to each case on age at case diagnosis (±2 years), sex, race/ethnicity, and year of program enrollment. Sex-specific and sensitivity analyses were performed. GRC age- and sex-adjusted standardized incidence ratios (SIRs) were compared with the Rochester Epidemiology Project (REP). Complete REP inpatient and outpatient medical records were reviewed by specialists. Conditions meeting standardized criteria on ≥2 visits were classified as REP confirmed cases. Results Six hundred and twenty-eight responders were diagnosed with autoimmune conditions between 2002 and 2017. In the nested case-control analyses, high WTC exposure was not associated with autoimmune domains and conditions (rheumatologic domain odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.77, 1.37; rheumatoid arthritis OR = 1.12, 95% CI = 0.70, 1.77). GRC members had lower SIR than REP. Women's risks were generally greater than men's. Conclusions The study found no statistically significant increased risk of autoimmune conditions with WTC exposures.

Background Septic cardiomyopathy worsens the prognosis of critically ill patients. Clinical data suggest that interleukin‐1β (IL‐1β), activated by the NLRP3 inflammasome, compromises cardiac function. Whether or not deleting Nlrp3 would prevent cardiac atrophy and improve diastolic cardiac function in sepsis was unclear. Here, we investigated the role of NLRP3/IL‐1β in sepsis‐induced cardiomyopathy and cardiac atrophy. Methods Male Nlrp3 knockout (KO) and wild‐type (WT) mice were exposed to polymicrobial sepsis by caecal ligation and puncture (CLP) surgery (KO, n = 27; WT, n = 33) to induce septic cardiomyopathy. Sham‐treated mice served as controls (KO, n = 11; WT, n = 16). Heart weights and morphology, echocardiography and analyses of gene and protein expression were used to evaluate septic cardiomyopathy and cardiac atrophy. IL‐1β effects on primary and immortalized cardiomyocytes were investigated by morphological and molecular analyses. IonOptix and real‐time deformability cytometry (RT‐DC) analysis were used to investigate functional and mechanical effects of IL‐1β on cardiomyocytes. Results Heart morphology and echocardiography revealed preserved systolic (stroke volume: WT sham vs. WT CLP: 33.1 ± 7.2 μL vs. 24.6 ± 8.7 μL, P

Background The factors associated with estimated glomerular filtrate rate (eGFR) decline in low risk adults remain relatively unknown. We hypothesized that a polygenic risk score (PRS) will be associated with eGFR decline. Methods We analyzed genetic data from 1,601 adult participants with European ancestry in the World Trade Center Health Program (baseline age 49.68 ± 8.79 years, 93% male, 23% hypertensive, 7% diabetic and 1% with cardiovascular disease) with ≥ three serial measures of serum creatinine. PRSs were calculated from an aggregation of single nucleotide polymorphisms (SNPs) from a recent, large-scale genome-wide association study (GWAS) of rapid eGFR decline. Generalized linear models were used to evaluate the association of PRS with renal outcomes: baseline eGFR and CKD stage, rate of change in eGFR, stable versus declining eGFR over a 3–5-year observation period. eGFR decline was defined in separate analyses as “clinical” (> -1.0 ml/min/1.73 m2/year) or “empirical” (lower most quartile of eGFR slopes). Results The mean baseline eGFR was ~ 86 ml/min/1.73 m2. Subjects with decline in eGFR were more likely to be diabetic. PRS was significantly associated with lower baseline eGFR (B = -0.96, p = 0.002), higher CKD stage (OR = 1.17, p = 0.010), decline in eGFR (OR = 1.14, p = 0.036) relative to stable eGFR, and the lower quartile of eGFR slopes (OR = 1.21, p = 0.008), after adjusting for established risk factors for CKD. Conclusion Common genetic variants are associated with eGFR decline in middle-aged adults with relatively low comorbidity burdens.

Effective risk factor modification is the prerequisite to prevent neurovascular disease such as stroke or vascular dementia. Non-traditional vascular risk factors (nt-vrfs) including stress significantly add to the risk of neurovascular disease arising from traditional vascular risk factors (t-vrfs). In order to discover sex-specific changes that may underlie previously reported inclines in the prevalence of neurovascular and cardiovascular disease in women, 10-year trends in the prevalence of vrfs in Switzerland were assessed.Anonymized data from 22,134 participants (51% women) of the governmental Swiss Health Survey, performed every 5 years (2007, 2012 and 2017), were obtained. Epidemiological parameters, t-vrfs and nt-vrfs were analyzed in a cross-sectional study design.Over the observation period, the number of women having full-time jobs increased considerably (2007 38%, 2012 39%, 2017 44%). This was accompanied by a substantial rise in the prevalence of nt-vrfs in women and men including stress at work (2007, not available; 2012 women/men 58%/60%; 2017 women/men 66%/65%), low locus of control (women/men: 2007 21%/19%, 2012 22%/19%, 2017 25%/22%) and sleep disorders (women/men: 2007 30%/22%, 2012 28%/20%, 2017 32%/26%). Amongst t-vrfs, only the prevalence of obesity and hypercholesterolemia increased over time in both sexes, whilst other t-vrfs remained stable (hypertension [27%], diabetes [5%]) or decreased (smoking [9.4 cigarettes/day]).A rise in women's economic participation alongside a higher affection with nt-vrfs in the female Swiss population emphasizes the need to improve vascular risk stratification and implement effective preventive measures for neurovascular and cardiovascular disease.

Background: Learning and learning-related neuroplasticity in motor cortex are potential mechanisms mediating recovery of movement abilities after stroke. These mechanisms depend on dopaminergic projections from midbrain that may encode reward information. Likewise, therapist experience confirms the role of feedback/reward for training efficacy after stroke. Objective: To test the hypothesis that rehabilitative training can be enhanced by adding performance feedback and monetary rewards. Methods: This multicentric, assessor-blinded, randomized controlled trial used the ArmeoSenso virtual reality rehabilitation system to train 37 first-ever subacute stroke patients in arm-reaching to moving targets. The rewarded group (n = 19) trained with performance feedback (gameplay) and contingent monetary reward. The control group (n = 18) used the same system without monetary reward and with graphically minimized performance feedback. Primary outcome was the change in the two-dimensional reaching space until the end of the intervention period. Secondary clinical assessments were performed at baseline, after 3 weeks of training (15 1-hour sessions), and at 3 month follow-up. Duration and intensity of the interventions as well as concomitant therapy were comparable between groups. Results: The two-dimensional reaching space showed an overall improvement but no difference between groups. The rewarded group, however, showed significantly greater improvements from baseline in secondary outcomes assessing arm activity (Box and Block Test at post-training: 6.03±2.95, P = .046 and 3 months: 9.66±3.11, P = .003; Wolf Motor Function Test [Score] at 3 months: .63±.22, P = .007) and arm impairment (Fugl-Meyer Upper Extremity at 3 months: 8.22±3.11, P = .011). Conclusions: Although neutral in its primary outcome, the trial signals a potential facilitating effect of reward on training-mediated improvement of arm pares, Neurorehabilitation and Neural Repair, 36 (2), ISSN:1545-9683, ISSN:0888-4390, ISSN:1552-6844

This study aimed to evaluate the effects of maternal exercise on alterations induced by prenatal stress in markers of the inflammatory process and the hypothalamic-pituitary-adrenal axis in the brain and lungs of neonatal mice. Female Balb/c mice were divided into three groups: control, prenatal restraint stress, prenatal restraint stress and physical exercise before and during the gestational period. On day 0 (PND0) and 10 (PND10), mice were euthanized for brain and lung analyses. The gene expression of GR, MR, IL-6, IL-10, and TNF in the brain and lungs and the protein expression of MMP-2 in the lungs were analyzed. Maternal exercise reduced IL-6 and IL-10 gene expression in the brain of PND0 mice. Prenatal stress and maternal exercise decreased GR, MR, IL-6, and TNF gene expression in the lungs of PND0 mice. In the hippocampus of PND10 females, exercise inhibited the effects of prenatal stress on the expression of MR, IL-6, and IL-10. In the lungs of PND10 females, exercise prevented the decrease in GR expression caused by prenatal stress. In the hippocampus and lungs of PND10 males, prenatal stress decreased GR gene expression. Our findings confirm the effects induced by prenatal stress and demonstrate that physical exercise before and during the gestational period may have a protective role on inflammatory changes.

Background: Individuals who participated in response efforts at the World Trade Center (WTC) following 9/11/2001 are experiencing elevated incidence of mild cognitive impairment (MCI) at midlife. Objective: We hypothesized that white matter connectivity measured using diffusion spectrum imaging (DSI) would be restructured in WTC responders with MCI versus cognitively unimpaired responders. Methods: Twenty responders (mean age 56; 10 MCI/10 unimpaired) recruited from an epidemiological study were characterized using NIA-AA criteria alongside controls matched on demographics (age/sex/occupation/race/education). Axial DSI was acquired on a 3T Siemen’s Biograph mMR scanner (12-channel head coil) using a multi-band diffusion sequence. Connectometry examined whole-brain tract-level differences in white matter integrity. Fractional anisotropy (FA), mean diffusivity (MD), and quantified anisotropy were extracted for region of interest (ROI) analyses using the Desikan-Killiany atlas. Results: Connectometry identified both increased and decreased connectivity within regions of the brains of responders with MCI identified in the corticothalamic pathway and cortico-striatal pathway that survived adjustment for multiple comparisons. MCI was also associated with higher FA values in five ROIs including in the rostral anterior cingulate; lower MD values in four ROIs including the left rostral anterior cingulate; and higher MD values in the right inferior circular insula. Analyses by cognitive domain revealed nominal associations in domains of response speed, verbal learning, verbal retention, and visuospatial learning. Conclusions: WTC responders with MCI at midlife showed early signs of neurodegeneration characterized by both increased and decreased white matter diffusivity in regions commonly affected by early-onset Alzheimer’s disease.

Postoperative major pulmonary complications (MPCs) continue to be leading causes of increased morbidity and death after cardiac surgery. Although various risk factors have been identified, reports on the association between sleep-disordered breathing (SDB) and postoperative MPCs remain inconclusive.What is the incidence of the composite end point postoperative MPCs? What are predictors for postoperative MPCs in patients without SDB, with OSA, and with central sleep apnea (CSA) who undergo cardiac surgery?In this subanalysis of the ongoing prospective observational study "Impact of Sleep-disordered breathing on Atrial Fibrillation and Perioperative complications in Patients undergoing Coronary Artery Bypass grafting Surgery (CONSIDER AF)," preoperative risk factors for postoperative MPCs were examined in 250 patients who underwent cardiac surgery. Postoperative MPCs (including respiratory failure, acute respiratory distress syndrome, pneumonia, or pulmonary embolism) were registered prospectively within the first seven postoperative days. Presence and type of SDB were assessed the night prior to surgery with the use of portable SDB-monitoring.Patients with SDB experienced significantly more often postoperative MPCs than patients without SDB (24% vs 7%; P .001). Multivariable logistic regression analysis showed that CSA (OR, 4.68 [95% CI, 1.78-12.26]; P = .002), heart failure (OR, 2.65 [95% CI, 1.11-6.31]; P = .028), and a history of transient ischemic attack or stroke (OR, 2.73 [95% CI, 1.07-6.94]; P = .035) were associated significantly with postoperative MPCs. Compared with patients without MPCs, those with postoperative MPCs had a significantly longer hospital stay (median days, 9 [25th/75th percentile, 7/13] vs 19 [25th/75th percentile, 11/38]; P .001).Among established risk factors for postoperative MPCs, CSA, heart failure, and history of transient ischemic attack or stroke were associated significantly with postoperative MPCs. Our findings contribute to the identification of patients who are at high-risk for postoperative MPCs.ClinicalTrials.gov identifier NCT02877745.

Background: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum–etoposide) showed a significant improvement in overall survival versus platinum–etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide alone. Methods: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum–etoposide, durvalumab plus platinum–etoposide, or platinum–etoposide alone. In all groups, patients received etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL/min or cisplatin 75–80 mg/m2 on day 1 of each cycle. Patients in the platinum–etoposide group received up to six cycles of platinum–etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum–etoposide versus platinum–etoposide and for durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. Findings: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum–etoposide, 268 to durvalumab plus platinum–etoposide, and 269 to platinum–etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3–27·9). Durvalumab plus tremelimumab plus platinum–etoposide was not associated with a significant improvement in overall survival versus platinum–etoposide (hazard ratio [HR] 0·82 [95% CI 0·68–1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6–12·0) versus 10·5 months (9·3–11·2). Durvalumab plus platinum–etoposide showed sustained improvement in overall survival versus platinum–etoposide (HR 0·75 [95% CI 0·62–0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3–14·7) versus 10·5 months (9·3–11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum–etoposide group, and 88 [33%] of 266 patients in the platinum–etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 85 (32%) in the durvalumab plus platinum–etoposide group, and 97 (36%) in the platinum–etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum–etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum–etoposide group (pancytopenia and thrombocytopenia [n=1 each]). Interpretation: First-line durvalumab plus platinum–etoposide showed sustained overall survival improvement versus platinum–etoposide but the addition of tremelimumab to durvalumab plus platinum–etoposide did not significantly improve outcomes versus platinum–etoposide. These results support the use of durvalumab plus platinum–etoposide as a new standard of care for the first-line treatment of ES-SCLC. Funding: AstraZeneca.

Morbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT) are still essentially affected by reactivation of cytomegalovirus (CMV). We evaluated 80 seropositive patients transplanted consecutively between March 2018 and March 2019 who received letermovir (LET) prophylaxis from engraftment until day +100 and retrospectively compared them with 80 patients without LET allografted between January 2017 and March 2018. The primary endpoint of this study was the cumulative incidence (CI) of clinically significant CMV infection (CS-CMVi) defined as CMV reactivation demanding preemptive treatment or CMV disease. With 14% CI of CS-CMVi at day +100 (11 events) was significantly lower in the LET cohort when compared to the control group (33 events, 41%; HR 0.29; p p = 0.002). One-year overall survival was 72% in the control arm vs 84% in the LET arm (HR 0.75 [95%CI 0.43–1.30]; p

Microvascular dysfunction plays a fundamental role in the pathogenesis of salivary gland disorders. Restoring and preserving microvascular integrity might therefore represent a promising strategy for the treatment of these pathologies. The mechanisms underlying microvascular dysfunction in salivary glands, however, are still obscure, partly due to the unavailability of adequate in vivo models. Here, we present a novel experimental approach that allows comprehensive in vivo analyses of the salivary gland microvasculature in mice. For this purpose, we employed different microscopy techniques including multi-photon in vivo microscopy to quantitatively analyze interactions of distinct immune cell subsets in the submandibular gland microvasculature required for their infiltration into the surrounding parenchyma and their effects on microvascular function. Confocal microscopy and multi-channel flow cytometry in tissue sections/homogenates complemented these real-time analyses by determining the molecular phenotype of the participating cells. To this end, we identified key adhesion and signaling molecules that regulate the subset- and tissue-specific trafficking of leukocytes into inflamed glands and control the associated microvascular leakage. Hence, we established an experimental approach that allows in vivo analyses of microvascular processes in healthy and diseased salivary glands. This enables us to delineate distinct pathogenetic factors as novel therapeutic targets in salivary gland diseases.

The transcription factor EB (TFEB) promotes protein degradation by the autophagy and lysosomal pathway (ALP) and overexpression of TFEB was suggested for the treatment of ALP-related diseases that often affect the heart. However, TFEB-mediated ALP induction may perturb cardiac stress response. We used adeno-associated viral vectors type 9 (AAV9) to overexpress TFEB (AAV9-Tfeb) or Luciferase-control (AAV9-Luc) in cardiomyocytes of 12-week-old male mice. Mice were subjected to transverse aortic constriction (TAC, 27G; AAV9-Luc: n = 9; AAV9-Tfeb: n = 14) or sham (AAV9-Luc: n = 9; AAV9-Tfeb: n = 9) surgery for 28 days. Heart morphology, echocardiography, gene expression, and protein levels were monitored. AAV9-Tfeb had no effect on cardiac structure and function in sham animals. TAC resulted in compensated left ventricular hypertrophy in AAV9-Luc mice. AAV9-Tfeb TAC mice showed a reduced LV ejection fraction and increased left ventricular diameters. Morphological, histological, and real-time PCR analyses showed increased heart weights, exaggerated fibrosis, and higher expression of stress markers and remodeling genes in AAV9-Tfeb TAC compared to AAV9-Luc TAC. RNA-sequencing, real-time PCR and Western Blot revealed a stronger ALP activation in the hearts of AAV9-Tfeb TAC mice. Cardiomyocyte-specific TFEB-overexpression promoted ALP gene expression during TAC, which was associated with heart failure. Treatment of ALP-related diseases by overexpression of TFEB warrants careful consideration.

An elevated risk of myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS), was identified among Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed firefighters. Further investigation was needed to determine if these findings were reproducible in a more heterogeneous WTC-exposed rescue/recovery workers cohort, the Stony Brook University-General Responder Cohort GRC (SBU-GRC). MGUS risk was compared between the cohorts and to published general population estimates from Olmsted County, MN, USA. In this observational seroprevalence study, odds ratios (OR) and age-standardized risk ratios (RR) of MGUS (M-spike and light-chain-MGUS combined), M-spike, and light-chain-MGUS were estimated using logistic regression. Age-standardized prevalences were calculated for white males aged 50–79; RRs were estimated by comparing risk in the WTC-exposed cohort with the Olmsted County screened cohort. SBU-GRC had elevated odds of MGUS compared with FDNY (OR = 1.38; 95%CI = 1.00–1.89). The age-standardized prevalence of MGUS was 9.0/100 persons (95%CI = 7.5–10.6), over two-fold higher than the general population (RR = 2.08; 95%CI = 1.72–2.51); the age-standardized prevalence of light-chain-MGUS was 3.5-fold higher (RR = 3.54; 95%CI = 2.52–4.97). This study adds to mounting evidence supporting an association between WTC/environmental exposures and MGUS among rescue/recovery workers. Access to MGUS screenings for the entire WTC-exposed cohort could allow for treatment interventions that improve survival.

Congenital hearing loss is a common disorder worldwide. Heterogeneous gene variation accounts for approximately 20-25% of such patients. We investigated a five-generation Chinese family with autosomal-dominant nonsyndromic sensorineural hearing loss (SNHL). No wave was detected in the pure-tone audiometry, and the auditory brainstem response was absent in all patients. Computed tomography of the patients, as well as of two sporadic SNHL cases, showed bilateral inner ear anomaly, cochlear maldevelopment, absence of the osseous spiral lamina, and an enlarged vestibular aqueduct. Such findings were absent in nonaffected persons. We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4KB gene (p.Gln121Arg) encoding phosphatidylinositol 4-kinase β (PI4KB) from the patients in this family. In addition, 3 missense PI4KB (p.Val434Gly, p.Glu667Lys, and p.Met739Arg) mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases. No such mutations were present within 600 Chinese controls, the 1000 genome project, gnomAD, or similar databases. Depleting pi4kb mRNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment, mimicking the patient phenotypes. Moreover, overexpression of 4 human missense PI4KB mutant mRNAs in zebrafish embryos resulted in impaired hearing function, suggesting dominant-negative effects. Taken together, our results reveal that PI4KB mutations can cause SNHL and inner ear malformation. PI4KB should be included in neonatal deafness screening.

Background: High blood pressure is the primary risk factor for cardiovascular death worldwide. Autosomal dominant hypertension with brachydactyly clinically resembles salt-resistant essential hypertension and causes death by stroke before 50 years of age. We recently implicated the gene encoding phosphodiesterase 3A ( PDE3A ); however, in vivo modeling of the genetic defect and thus showing an involvement of mutant PDE3A is lacking. Methods: We used genetic mapping, sequencing, transgenic technology, CRISPR-Cas9 gene editing, immunoblotting, and fluorescence resonance energy transfer. We identified new patients, performed extensive animal phenotyping, and explored new signaling pathways. Results: We describe a novel mutation within a 15 base pair (bp) region of the PDE3A gene and define this segment as a mutational hotspot in hypertension with brachydactyly. The mutations cause an increase in enzyme activity. A CRISPR/Cas9-generated rat model, with a 9-bp deletion within the hotspot analogous to a human deletion, recapitulates hypertension with brachydactyly. In mice, mutant transgenic PDE3A overexpression in smooth muscle cells confirmed that mutant PDE3A causes hypertension. The mutant PDE3A enzymes display consistent changes in their phosphorylation and an increased interaction with the 14-3-3θ adaptor protein. This aberrant signaling is associated with an increase in vascular smooth muscle cell proliferation and changes in vessel morphology and function. Conclusions: The mutated PDE3A gene drives mechanisms that increase peripheral vascular resistance causing hypertension. We present 2 new animal models that will serve to elucidate the underlying mechanisms further. Our findings could facilitate the search for new antihypertensive treatments.

Recent guideline changes for lung cancer screening with low-dose computed tomography recommend smoking-cessation interventions be done in parallel with screening. The purpose of this study is to determine the post-guideline rates of smoking-cessation interventions among patients eligible and ineligible for lung cancer screening.Using electronic health records collected from a large ambulatory care system in northern California between 2010 and 2017, authors identified new patients who were current smokers aged 55-80 years visiting a primary care provider, and grouped patients into lung cancer screening-eligible heavy smokers, screening-ineligible moderate smokers, and screening-ineligible light smokers. Screening-eligible smokers versus screening-ineligible smokers were compared in receipt of smoking-cessation interventions before (2010-2013) and after (2014-2017) the guideline change, overall and by intervention type (formal counseling, informal counseling, pharmacotherapy) using hierarchical generalized linear models. Analyses were conducted in 2018-2019.After the guideline change, the likelihood of receiving any smoking-cessation intervention (OR=1.44, 95% CI=1.28, 1.61, p0.05), informal counseling (OR=1.29, 95% CI=1.15, 1.46, p0.05), and pharmacotherapy (OR=1.24, 95% CI=1.02, 1.50, p0.05) during a new patient visit significantly increased, with the increase not varying by level of smoking. For formal counseling, the post-guideline increase was greater for screening-eligible heavy smokers (OR=3.15, 95% CI=1.18, 8.36, p0.05) and moderate smokers (OR=3.58, 95% CI=1.29, 9.95, p0.05) relative to light smokers.Smoking-cessation interventions increased after new lung cancer screening guidelines. Given the sizable adverse impacts of smoking on morbidity and mortality, small increases in the implementation of smoking-cessation interventions could have substantial public health benefits.

ObjectiveTo evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after IV thrombolysis (IVT), we analyzed a cohort of 1,919 patients with stroke with type 2 diabetes mellitus in a multicenter exploratory analysis.MethodsData from patients with diabetes and ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET.ResultsOf 1,919 patients with stroke with type 2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1,162 (61%) had not (MET−). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets, or antihypertensives were more common in the MET+ group. After PSM, the 2 groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIH Stroke Scale 10.0 ± 6.7 vs 11.3 ± 6.5), 3-month degree of independence on modified Rankin Scale (2 [interquartile range (IQR) 1.0–4.0] vs 3 [IQR 1.0–4.0]), as well as mortality (12.5% vs 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well-balanced between the groups.ConclusionsPatients with stroke and diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.

Crossed cerebellar diaschisis (CCD) in internal carotid artery (ICA) stroke refers to attenuated blood flow and energy metabolism in the contralateral cerebellar hemisphere. CCD is associated with an interruption of cerebro-cerebellar tracts, but the precise mechanism is unknown. We hypothesized that in patients with ICA occlusions, CCD might indicate severe hemodynamic impairment in addition to tissue damage. Duplex sonography and clinical data from stroke patients with unilateral ICAO who underwent blood oxygen-level-dependent MRI cerebrovascular reserve (BOLD-CVR) assessment were analysed. The presence of CCD (either CCD+ or CCD−) was inferred from BOLD-CVR. We considered regions with negative BOLD-CVR signal as areas suffering from hemodynamic steal. Twenty-five patients were included (11 CCD+ and 14 CCD−). Stroke deficits on admission and at 3 months were more severe in the CCD+ group. While infarct volumes were similar, CCD+ patients had markedly larger BOLD steal volumes than CCD− patients (median [IQR] 122.2 [111] vs. 11.6 [50.6] ml; p

Purpose Cardiorespiratory fitness (CRF) seems to be prognostic prior to allogeneic stem cell transplantation (allo-HSCT). Influencing factors of CRF in allo-HSCT candidates have not been studied so far. Aim was to identify potentially influencing factors on CRF. Methods To assess CRF, a maximal cardiopulmonary exercise test (CPET) was performed on average 2.6 ± 7.2 days prior to admission. A regression analysis was conducted, with the following predictors: gender, age, body mass index (BMI), time between last therapy and allo-HSCT (t_Therapies), number of cardiotoxic therapies (n_Cardiotox), number of transplantations (n_Transplantations), comorbidity index (HCT-CI), hemoglobin level of the last 3 months (area under the curve), and physical activity. Results A total of 194 patients performed a CPET. VO2peak was significantly reduced compared with reference data. In total, VO2peak was 21.4 ml/min/kg (− 27.5%, p p 2peak was significantly (p Conclusions Our study demonstrates a decreased CRF indicating the potential need of prehabilitative exercise. We revealed some influencing factors on CRF. Those patients could benefit the most from exercise.

A genetic influence on blood pressure was demonstrated more than 100 years ago and a simple Mendelian inheritance was initially presumed. Platt and Pickering conducted a lively debate on this topic. Platt favored the idea that a single gene or only a few genes were responsible for high blood pressure. Pickering presented research results, which supported the assumption that many genes exerted an influence on blood pressure. This was all in a period when it was not even known what genes were. Genome-wide association studies (GWAS) according to the Pickering model have identified 500 blood pressure relevant gene loci, which are distributed over the whole genome. Each individual gene exerts only a small effect on blood pressure. The dark horses of hypertension research are the secondary causes. In pheochromocytoma, primary aldosteronism, Cushing's syndrome and even fibromuscular dysplasia (renovascular hypertension) the results indicate that a genetic cause regularly underlies secondary hypertension. This would therefore also partially confirm Platt's theory. In the meantime, a multitude of forms of hypertension have been described with a genetic inheritance according to Mendel. Each of these genetic variants exerts a considerable influence on blood pressure. A multitude of novel physiological mechanisms were explained by this. These findings will become therapeutically important. Therefore, it is incumbent upon clinicians to be optimally informed about these research results.Vor über 100 Jahren wurde ein genetischer Einfluss auf den Blutdruck nachgewiesen und ein einfacher Erbgang gemäß den Mendel-Regeln vermutet. Platt und Pickering führten eine lebhafte Debatte über dieses Thema. Platt favorisierte die Idee, dass ein einzelnes Gen oder nur wenige Gene für den Bluthochdruck verantwortlich seien. Pickering legte Forschungsergebnisse vor, die vermuten ließen, dass viele Gene Einfluss auf den Blutdruck ausüben. Dies alles in einer Zeit, in der man noch nicht wusste, was Gene überhaupt sind. Genomweite Assoziationsstudien (GWAS) nach dem Pickering-Modell weisen auf 500 blutdruckrelevante Genloci hin, die über das gesamte Genom verteilt sind. Jedes einzelne Gen übt nur einen kleinen Einfluss auf den Blutdruck aus. Als Außenseiter der Hochdruckforschung gelten sekundäre Ursachen. Bei Phäochromozytom, Aldosteronismus, Cushing-Syndrom und sogar bei der fibromuskulären Dysplasie (renovaskuläre Hypertonie) lassen die Ergebnisse darauf schließen, dass der sekundären Hypertonie regelmäßig eine genetische Ursache zugrunde liegt. Damit wurde auch die Theorie von Platt teilweise bestätigt. Mittlerweile wurde eine Vielzahl von Hypertonieformen mit einem genetischen Erbgang nach Mendel beschrieben. Jede dieser Genvarianten übt einen beträchtlichen Einfluss auf den Blutdruck aus. Eine Vielzahl neuer physiologischer Mechanismen wurde dadurch aufgeklärt. Diese Befunde werden therapeutische Bedeutung haben. Also obliegt es den Klinikern, über diese Forschungsergebnisse bestens informiert zu sein.

OBJECTIVE To explore attitudes toward immigrants and refugees living in Ecuador. DESIGN AND MEASURES A transnationalism framework informed this qualitative study, which utilized a semi-structured interview guide to elicit responses from participants about their attitudes toward immigrants and refugees. Interviews were conducted in Spanish, audio-taped, transcribed, coded, and analyzed in Spanish to identify emergent themes. Demographic data were analyzed using SPSS. SAMPLE Participants (n = 50) were recruited from five sectors that interact with refugees: health care, the press, the police, nongovernmental organizations, and education. Fifty interviews were conducted with adults in Quito, Ecuador, in 2017. RESULTS Participants reported concerns about the health and well-being of immigrants and refugees, expressed a willingness to assist them, but within limits, noted discrimination and bias against refugees, and cited social policies and human rights as factors that influenced their attitudes. CONCLUSIONS Our findings indicate that immigrants and refugees face challenges which impact their health and well-being, according to participants in the study. Social policies can influence attitudes, but are also affected by rapidly shifting immigration patterns. Migration flows in South America is an under-studied area of research, with opportunity for further public health nursing inquiry.

With more than 1.5 million Small Incision Lenticule Extraction (SMILE) procedures having already been performed worldwide in an ageing population, intraocular lens (IOL) power calculation in post-SMILE eyes will inevitably become a common challenge for ophthalmologists. Since no refractive outcomes of cataract surgery following SMILE have been published, there is a lack of empirical data for optimizing IOL power calculation. Using the ray tracing as the standard of reference – a purely physical method that obviates the need for any empirical optimization - we analyzed the agreement of various IOL power calculation formulas derived from the American Society of Cataract and Refractive Surgeons (ASCRS) post-keratorefractive surgery online calculator. In our study of 88 post-SMILE eyes, the Masket formula showed the smallest mean prediction error [−0.36 ± 0.32 diopters (D)] and median absolute error (0.33D) and yielded the largest percentage of eyes within ±0.50D (70%) in reference to ray tracing. Non-inferior refractive prediction errors and ±0.50D accuracies were achieved by the Barrett True K, Barrett True K No History and the Potvin-Hill formula. Use of these formulas in conjunction with ray tracing is recommended until sufficient data for empirical optimization of IOL power calculation after SMILE is available.

Background Parkinson’s disease (PD) and essential tremor (ET) are neurodegenerative diseases characterized by movement deficits. Especially in PD, maintaining cyclic movement can be significantly disturbed due to pathological changes in the basal ganglia and the cerebellum. Providing external cues improves timing of these movements in PD and also affects ET. The aim of this study is to determine differences in cortical activation patterns in PD and ET patients during externally and internally cued movements. Methods Eleven PD patients, twelve ET patients, OFF tremor suppressing medication, and nineteen age-matched healthy controls (HC) were included and asked to perform a bimanual tapping task at two predefined cue frequencies. The auditory cue, a metronome sound presented at 2 or 4 Hz, was alternately switched on and off every 30 s. Tapping at two different frequencies were used since it is expected that different brain networks are involved at different frequencies as has been shown in previous studies. Cortical activity was recorded using a 64-channel EEG cap. To establish the cortical activation pattern in each group, the task related power (TRP) was calculated for each subject. For inter-groups analysis, EEG electrodes for divided into 5 different areas. Results Inter-group analysis revealed significant differences in areas responsible for motor planning, organization and regulation and involved in initiation, maintenance, coordination and planning of complex sequences of movements. Within the area of the primary motor cortex the ET group showed a significantly lower TRP than the HC group. In the area responsible for combining somatosensory, auditory and visual information both patient groups had a higher TRP than the HC group. Conclusions Different neurological networks are involved during cued and non-cued movements in ET, PD and HC. Distinct cortical activation patterns were revealed using task related power calculations. Different activation patterns were revealed during the 2 and 4 Hz tapping task indicating different strategies to execute movements at these rates. The results suggest that a including a cued/non-cued tapping task during clinical decision making could be a valuable tool in an objective diagnostic protocol.

PURPOSE: To compare the safety, efficacy, and patient-reported quality of vision of small incision lenticule extraction (SMILE) and implantable Collamer lens (ICL) implantation for the treatment of high myopia. METHODS: A database of 1,634 SMILE (Carl Zeiss Meditec AG, Jena, Germany) and 225 ICL implantation (STAAR Surgical, Monrovia, CA) procedures was screened for patients with a binocular preoperative manifest refraction spherical equivalent between −6.00 and −10.00 diopters (D) and plano target refraction. One-to-one matching was performed by preoperative manifest refraction spherical equivalent, age, and pupil size. All identified patients were then prospectively examined at their next regular postoperative follow-up visit and presented with the standardized and clinically validated Quality of Vision questionnaire to gauge patient-reported postoperative visual quality. RESULTS: A total of 80 eyes (40 patients) were eligible for 1:1 matching. Mean postoperative follow-up was 27.8 ± 14.3 months in the SMILE group and 26.6 ± 17.7 months in the ICL group ( P = .44). Regarding the percentage of eyes within ±0.50 D of plano target, refractive predictability was better in eyes treated with ICL implantation (90%) than SMILE (72.5%) ( P = .045). Mean UDVA was comparable (ICL: −0.09 ± 0.10 logMAR; SMILE: −0.06 ± 0.09 logMAR; P < .09), but the efficacy (1.28 vs 1.05; P < .001) and safety (1.31 ± 0.22 vs 1.10 ± 0.25; P < .001) indices were higher after ICL implantation. ICL implantation induced significantly fewer higher order aberrations (total higher order aberrations: SMILE 0.724 ± 0.174 µm vs ICL 0.436 ± 0.114 µm; P < .01). Regarding subjective quality of vision, patients who had ICL implantation were significantly less bothered by visual disturbances, which were mainly halos after ICL and starbursts and fluctuations of vision after SMILE ( P < .05). CONCLUSIONS: In this refraction-matched comparative study, ICL implantation for high myopia yielded better refractive accuracy, better uncorrected distance visual acuity, fewer higher order aberrations, and better subjective quality of vision than SMILE. [ J Refract Surg . 2020;36(3):150–159.]

Purpose To determine the anatomical and functional outcomes of an extended 6-month intravitreal anti-vascular endothelial growth factor (anti-VEGF) upload in choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR). Methods A retrospective database analysis was performed applying the following inclusion criteria: (1) diagnosis of CSCR, (2) diagnosis of secondary CNV, and (3) treatment of at least six consecutive injections of anti-VEGF. Outcome measures included the change of central retinal subfield thickness, remodeling of the pigment epithelium detachments, and change in visual function. Results Twenty-one eyes of 21 patients were included. Mean patient age was 65 ± 8.3 years, and 35% of the patients (n = 8) were female. Mean disease duration before diagnosis of CNV was 48 ± 25.3 months. Mean central retinal thickness decreased from 346 ± 61 to 257 ± 57 μm (p p p = 0.038). Significant CNV remodeling was observed as a decrease in pigment epithelium detachment (PED) vertical (p = 0.021) and horizontal diameter (p = 0.024) as well as PED height (p Conclusion An extended anti-VEGF upload of six consecutive injections seems to be effective in inducing CNV remodeling and fluid resorption in CNV complicating chronic CSCR.

Background According to the Joint Theater Trauma Registry, 26% to 33% of war casualties develop acute respiratory distress syndrome (ARDS), with high mortality. Here, we aimed to describe ARDS incidence and severity among patients evacuated from war zones and admitted to French intensive care units (ICUs). Methods We performed an observational retrospective multicentric review of all patients evacuated from war zones and admitted to French ICUs between 2003 and 2018. Our analysis included all medical and trauma patients developing ARDS according to the Berlin definition. We evaluated ARDS incidence, and determined ARDS severity from arterial blood gas analysis. Analyzed parameters included invasive ventilation duration, ARDS treatments, ICU stay length, and 30-day and 90-day mortalities. Results Among 141 included patients (84% military; median age, 30 years), 57 (42%) developed ARDS. Acute respiratory distress syndrome was mild in 13 (22%) patients, moderate in 24 (42%) patients, and severe in 20 (36%) patients. Evacuation occurred in less than 26 hours for 32 war casualties, 17 non-war-related trauma patients, and 8 medical patients. Among severe trauma patients, median Injury Severity Score was 34, and Abbreviated Injury Scale thorax was 3. Upon French ICU admission, median partial pressure of oxygen in arterial blood/inspirated fraction of oxygen ratio was 241 [144-296]. Administered ARDS treatments included intubation (98%, n = 56), protective ventilation (87%, n = 49), neuromuscular blockade (76%, n = 43), prone position (16%, n = 9), inhaled nitric oxide (10%, n = 6), almitrine (7%, n = 7), and extracorporeal life support (4%, n = 2). Median duration of invasive ventilation was 13 days, ICU stay was 18 days, 30-day mortality was 14%, and 90-day mortality was 21%. Conclusion Acute respiratory distress syndrome was frequent and severe among French patients evacuated from war theaters. Improved treatment capacities are needed in the forward environment-for example, a specialized US team can provide extracorporeal life support for highly hypoxemic war casualties. Level of evidence Prognostic and epidemiological study, level III.

BACKGROUND Chronic graft-versus-host disease (cGVHD) represents a double-edged sword. In its nonsevere form, cGVHD associates with better control of the malignant disease, thus highlighting graft-versus-leukemia effects. However, severe cGVHD leads to debilitating morbidity and increased nonrelapse mortality. The prediction of severe cGVHD, in particular at disease onset, is therefore of high importance for ensuing clinical decisions and overall success of allogeneic stem cell transplantations. CXC-chemokine ligand 9 (CXCL9) is an interferon-inducible chemokine of the CXC family and is increased in cGVHD. Endothelial activation and stress index (EASIX) was shown to predict death after acute graft-versus-host disease. We explored CXCL9 and EASIX as predictors of severe cGVHD. METHODS Sera and clinical data of 480 patients were available who survived at least 6 months following allogeneic stem cell transplantation without steroid-refractory acute graft-versus-host disease and without early relapse. CXCL9 and EASIX were measured on day +100 and onset of cGVHD. RESULTS Development of nonsevere cGVHD was significantly associated with improved overall survival (hazard ratio 0.53, P < 0.001). CXCL9 serum levels at the onset of cGVHD predicted the development of severe cGVHD later on (hazard ratio 1.33, P = 0.02). In contrast, EASIX at the onset of cGVHD was not associated with cGVHD severity but was a significant independent risk factor for overall mortality and nonrelapse mortality. CONCLUSIONS CXCL9 levels at the onset of cGVHD can help to predict severe courses of the disease and have potential for optimizing tailored administration of immunosuppressive therapy.

Objective The ability to experience positive affect (PA) has clinical and quality of life implications, particularly in vulnerable populations such as trauma-exposed disaster responders. Low PA is included in the diagnostic criteria for posttraumatic stress disorder (PTSD), however evidence for PA reduction in PTSD has been mixed. In contrast, negative affect (NA) has consistently been found to be elevated among individuals with PTSD. Multiday, ecological momentary assessment (EMA) can provide more ecologically valid evidence about experiences of affect; however, no such studies have been conducted in traumatized individuals with PTSD to date. Method World Trade Center (WTC) responders (N = 202) oversampled for the presence of PTSD were recruited from the WTC Health Program. Participants were administrated the Structured Clinical Interview for DSM-IV and the PTSD Checklist for DSM-5 at baseline, then completed EMA surveys of affect four times a day over seven consecutive days. Results Participants with current PTSD (19.3% of the sample) showed significantly higher levels of daily NA compared with those without PTSD. However, there was no group difference in daily PA, nor was PA associated with a dimensional measure of PTSD. Conclusion Results suggest that for chronic PTSD among disaster responders, positive emotions are not inhibited across daily living. Such findings add to evidence suggesting that PA reduction may not be diagnostically relevant to PTSD, whereas NA remains an important target for therapeutic interventions. Moreover, results show that WTC responders can experience and benefit from positive emotion, even if they continue to have PTSD symptoms. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Testosterone is an important determinant of endothelial function and vascular health in men. As both factors play a role in mortality after allogeneic stem cell transplantation (alloSCT), we retrospectively evaluated the impact of pre-transplant testosterone levels on outcome in male patients undergoing alloSCT. In the discovery cohort (n=346), an impact on outcome was observed only in the subgroup of patients allografted for acute myeloid leukemia (AML) (n=176, hereafter termed 'training cohort'). In the training cohort, lower pre-transplant testosterone levels were significantly associated with shorter overall survival (OS) [hazard ratio (HR) for a decrease of 100 ng/dL: 1.11, P=0.045]. This was based on a higher hazard of non-relapse mortality (NRM) (cause-specific HR: 1.25, P=0.013), but not relapse (cause-specific HR: 1.06, P=0.277) in the multivariable models. These findings were replicated in a confirmation cohort of 168 male patients allografted for AML in a different center (OS, HR: 1.15, P=0.012 and NRM, cause-specific HR: 1.23; P=0.008). Next, an optimized cut-off point for pre-transplant testosterone was derived from the training set and evaluated in the confirmation cohort. In multivariable models, low pre-transplant testosterone status (

Background Blood pressure variability (BPV) is associated with outcome after endovascular thrombectomy in acute large vessel occlusion stroke. We aimed to provide the optimal sampling frequency and BPV index for outcome prediction by using high-resolution blood pressure (BP) data. Methods Patient characteristics, 3-month outcome, and BP values measured intraarterially at 1 Hz for up to 24 h were extracted from 34 patients treated at a tertiary care center neurocritical care unit. Outcome was dichotomized (modified Rankin Scale 0–2, favorable, and 3–6, unfavorable) and associated with systolic BPV (as calculated by using standard deviation, coefficient of variation, averaged real variability, successive variation, number of trend changes, and a spectral approach using the power of specific BP frequencies). BP values were downsampled by either averaging or omitting all BP values within each prespecified time bin to compare the different sampling rates. Results Out of 34 patients (age 72 ± 12.7 years, 67.6% men), 10 (29.4%) achieved a favorable functional outcome and 24 (70.6%) had an unfavorable functional outcome at 3 months. No group differences were found in mean absolute systolic BP (SBP) (130 ± 18 mm Hg, p = 0.82) and diastolic BP (DBP) (59 ± 10 mm Hg, p = 1.00) during the monitoring time. BPV only reached predictive significance when using successive variation extracted from downsampled (averaged over 5 min) SBP data (median 4.8 mm Hg [range 3.8–7.1]) in patients with favorable versus 7.1 mmHg [range 5.5–9.7] in those with unfavorable outcome, area under the curve = 0.74 [confidence interval (CI) 0.57–0.85; p = 0.031], or the power of midrange frequencies between 1/20 and 1/5 min [area under the curve = 0.75 (CI 0.59–0.86), p = 0.020]. Conclusions Using high-resolution BP data of 1 Hz, downsampling by averaging all BP values within 5-min intervals is essential to find relevant differences in systolic BPV, as noise can be avoided (confirmed by the significance of the power of midrange frequencies). These results demonstrate how high-resolution BP data can be processed for effective outcome prediction.

BACKGROUND Physical activity improves insulin sensitivity in obesity. Hypoxia training is claimed to augment this effect. We tested the hypothesis that normobaric hypoxia training would improve insulin sensitivity in obese patients with metabolic syndrome. METHODS In a randomized controlled trial, 23 obese men with metabolic syndrome who were not informed of the FiO2 conditions underwent a 6-week physical exercise intervention under ambient (n = 11; FiO2 21%) conditions or hypoxia (n = 12; FiO2 15%) using a normobaric hypoxic chamber. Three 60-min sessions of interval training were performed each week at 60% of individual VO2max. Assessment of myocellular insulin sensitivity by euglycemic hyperinsulinemic clamp was performed in 21 of these subjects before and after 6 weeks of training. Comprehensive phenotyping also included biopsies of subcutaneous adipose tissues. RESULTS The intermittent moderate physical exercise protocol did not substantially change the myocellular insulin sensitivity within 6 weeks under normoxic conditions (ISIClamp: 0.035 (IQR 0.016-0.075) vs. 0.037 (IQR 0.026-0.056) mg* kg-1 *min-1/(mU* l-1); p = 0.767). In contrast, ISIClamp improved during hypoxia training (0.028 (IQR 0.018-0.035) vs. 0.038 (IQR 0.024-0.060) mg * kg-1 *min-1/(mU *l-1); p

The goal of the present work was to examine clinical risk factors for mortality in 1375 COVID + patients admitted to a hospital in Suffolk County, NY. Data were collated by the hospital epidemiological service for patients admitted from 3/7/2020 to 9/1/2020. Time until final discharge or death was the outcome. Cox proportional hazards models were used to estimate time until death among admitted patients. In total, all cases had resolved leading to 207 deaths. Length of stay was significantly longer in those who died as compared to those who did not (p = 0.007). Of patients who had been discharged, 54 were readmitted and nine subsequently died. Multivariable-adjusted Cox proportional hazards regression revealed that in addition to older age, male sex, and a history of chronic heart failure, chronic obstructive pulmonary disease, and diabetes, that a history of premorbid depression was a risk factors for COVID-19 mortality (aHR = 2.42 [1.38–4.23] P = 0.002), and that this association remained after adjusting for age and for neuropsychiatric conditions as well as medical comorbidities including cardiovascular disease and pulmonary conditions. Sex-stratified analyses revealed that associations between mortality and depression was strongest in males (aHR = 4.45 [2.04–9.72], P

Surgical nerve transfers are used to efficiently treat peripheral nerve injuries, neuromas, phantom limb pain, or improve bionic prosthetic control. Commonly, one donor nerve is transferred to one target muscle. However, the transfer of multiple nerves onto a single target muscle may increase the number of muscle signals for myoelectric prosthetic control and facilitate the treatment of multiple neuromas. Currently, no experimental models are available. This study describes a novel experimental model to investigate the neurophysiological effects of peripheral double nerve transfers to a common target muscle. In 62 male Sprague-Dawley rats, the ulnar nerve of the antebrachium alone (n=30) or together with the anterior interosseus nerve (n=32) was transferred to reinnervate the long head of the biceps brachii. Before neurotization, the motor branch to the biceps’ long head was transected at the motor entry point. Twelve weeks after surgery, muscle response to neurotomy, behavioral testing, retrograde labeling, and structural analyses were performed to assess reinnervation. These analyses indicated that all nerves successfully reinnervated the target muscle. No aberrant reinnervation was observed by the originally innervating nerve. Our observations suggest a minimal burden for the animal with no signs of functional deficit in daily activities or auto-mutilation in both procedures. Furthermore, standard neurophysiological analyses for nerve and muscle regeneration were applicable. This newly developed nerve transfer model allows for the reliable and standardized investigation of neural and functional changes following the transfer of multiple donor nerves to one target muscle.

Little is known about the connection between preoperative keratometry and postoperative results of myopic small-incision lenticule extraction (SMILE). To determine the influence of extreme (flat and steep) corneal keratometry on the safety and efficacy of SMILE, the databases of the Department of Ophthalmology, Ludwig-Maximilians-University Munich, Germany, and SMILE Eyes Linz, Austria, were screened for patients with steep and flat keratometry who had undergone SMILE. In this cross-sectional matched comparative cohort study, eyes with markedly flat (

The present study aimed to evaluate the effects of treadmill maternal exercise on alterations induced by prenatal stress in neonatal mice. Female and male Balb/c mice were divided into five groups: control (CON), prenatal restraint stress (PNS), prenatal restraint stress and physical exercise before pregnancy (PNS + EX1), prenatal restraint stress and physical exercise during pregnancy (PNS + EX2), and prenatal restraint stress and physical exercise before and during pregnancy (PNS + EX3). Exercise was performed using a treadmill, at a speed of 10 m/min, for 60 min, 5 days a week. Maternal behavior was assessed on days 3, 4 and 5 postpartum (PPD). Placental gene expression of glucocorticoid receptor (GR), 11-β-hydroxysteroid dehydrogenase 2 (11β-HSD2), 5-hydroxytryptamine receptor 1A (5HT