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Introduction Studies demonstrate the connection between adverse sexual function and medical conditions such as diabetes and heart disease. However, in the areas of spinal and spinal cord pathologies that require surgical interventions, there are scant data. Objectives We undertook a narrative review to synthesize what is known on the topic, raise awareness, and call for action. Methods PubMed and Google Scholar identified case reports and primary studies evaluating female sexual dysfunction associated with spinal pathology as well as surgical intervention success were reviewed to contextualize and characterize female sexual dysfunction. Results Available case reports and primary studies suggest that female sexual dysfunction can result from traumatic spinal etiologies, malignant tumors, and benign tumors with and without bony involvement. Although identified as a key preoperative predictor in maintenance or improvement of neurologic status, sexuality is rarely addressed in the neurosurgical care plan. In spinal stenosis and degenerative spine disease, over half of patients report pain with sexual activity. Importantly, while pain can hinder sexual activity in females, there are other sexual issues, including desire and subjective arousal, lubrication, orgasm, and satisfaction that are usually not explored. Studies show the impact of spinal pathologies on frequency of sexual intercourse, hypoesthesia, anorgasmia, and depression. Surgical intervention of spinal pathologies has been cited to improve back pain however other types of sexual dysfunction usually fails to improve after surgical intervention. Conclusions The lack of high-quality research with adequate numbers of female participants that appropriately characterizes the nuances of female sexual dysfunction across various spinal pathologies, with post-surgical intervention analysis and consideration of surgical approach, necessitates consideration for future study. A pre-op and post-op sexual history in all woman undergoing spinal surgery should be a standard of care.

Evidence on associations of lifestyle factors with Alzheimer's pathology and cognition are ambiguous, potentially because they rarely addressed inter-relationships of factors and sex effects. While considering these aspects, we examined the relationships of lifestyle factors with brain amyloid burden and cognition.We studied 178 cognitively normal individuals (women, 49%; 65.0 [7.6] years) and 54 individuals with mild cognitive impairment (women, 35%; 71.3 [8.3] years) enrolled in a prospective study of volunteers who completedOverall, higher cognitive activity was associated with better cognitive performance and higher physical activity was associated with lower amyloid burden. The latter association was weakened to a nonsignificant level after excluding multivariate outliers. Examination of the moderating effect of sex in the model revealed an inverse association of metabolic/vascular risk with cognition in men, whereas in women metabolic/vascular risk trended toward increased amyloid burden. Furthermore, a significant inverse association between physical activity and amyloid burden was found only in men. Inheritance of an APOE4 allele was associated with higher amyloid burden only in women.Sex modifies effects of certain lifestyle-related factors on amyloid burden and cognition. Notably, our results suggest that the negative impact of metabolic/vascular risk influences the risk of cognitive decline and Alzheimer's disease through distinct paths in women and men. ANN NEUROL 2022;92:451-463.

To analyze the presence of fetal myocardial dysfunction in intrahepatic cholestasis of pregnancy (ICP) at diagnosis.This prospective cohort study included 49 pregnant participants with ICP at diagnosis and 49 nonaffected controls from a single public hospital. ICP was diagnosed based on clinical symptoms after excluding other causes of pruritus and presence of autoimmune diseases. Total bile acids were not obtained in this cohort. ICP pregnancies were assessed with a functional echocardiography at diagnosis including PR-interval, isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) for electrical, systolic, and diastolic function, respectively. Controls were assessed at recruitment. Perinatal outcomes were obtained from delivery books. The main outcome was the presence of PR-interval prolongation or first-degree fetal heart block, and echographic signs of diastolic and systolic dysfunction.Compared to controls, ICP were above upper limit in conjugated bilirubin (2.0% vs. 20.4%; p = 0.008), aspartate aminotransferase (2.0% vs. 24.5%; p = 0.002), and alanine aminotransferase (4.1% vs. 28.6%; p = 0.002). ICP was associated with a higher PR-interval (130 ± 12 ms vs. 121 ± 6 ms; p 0.0001) with five first-degree fetal heart blocks. IRT was significantly higher in ICP (42 ± 6 ms vs. 37 ± 5 ms; p = 0.0001), with no differences in ICT and ET. PR-interval trend was only positively correlated with IRT in ICP pregnancies (p = 0.04 and p = 0.34, in ICP and controls, respectively).Our study demonstrates that fetuses affected by maternal ICP are associated with electrical and diastolic myocardial dysfunction. More studies focused on antenatal and postnatal functional echocardiography are necessary to validate our results and consider these markers in the clinical management of ICP pregnancies.

Purpose: The aim of this study was to evaluate the anastomotic leakage (AL) rate and predictors for AL following minimally invasive restorative rectal resection (RRR) among rectal cancer patients managed according to up-to-date standardized treatment. Furthermore, we explored the impact of symptomatic AL on long-term survival. Methods: The study cohort was rectal cancer patients undergoing minimally invasive RRR in Central Denmark Region between 2013 and 2017. Data was retrieved from a prospective clinical quality database and supplemented with data from medical records. The AL rate was calculated as the proportion of patients who developed symptomatic AL within 30 days. Predictors for AL were identified through logistic regression. The impact of AL on long-term survival was analyzed using Kaplan–Meier methods and Cox regression. Results: AL occurred in 15.1% of 604 patients. The AL rate for males was 20.1% (95% CI 16.3–24.3) and 5.0% (95% CI 2.4–9.0) for females. Odds ratio (OR) of AL in females vs. males was 0.25 (95% CI 0.12–0.51). The use of at least three firings when transecting the rectum was associated with OR of 2.71 (95% CI 1.17–6.26) for AL. The 5-year survival for patients with vs. those without AL was 76.1% (95%CI 65.1–84.0) and 83.6% (95%CI 79.8–86.7), corresponding to adjusted hazard ratio of 1.43 (95%CI 0.84–2.41). Conclusion: Symptomatic AL is still a challenge in a standardized setting using minimally invasive surgery in rectal cancer patients undergoing RRR, especially in men. Multiple firings should be avoided in transection of the rectum with an endoscopic stapler. AL had a statistical non-significant negative impact on survival.

This study assessed whether the use of a peer-to-peer educational book, written and illustrated by women who experienced common mental disorders (CMDs) in the perinatal period, can positively impact women's knowledge and attitudes about these conditions.This one-group pretest/posttest survey assessed participants' knowledge and attitudes regarding CMDs immediately before and after reading INSPIRE: Stories of Motherhood. The book is composed of women's stories and artwork about their own experiences with parenthood, with an emphasis on the challenges of parenthood and depictions of CMDs, depression and anxiety, during the peripartum period. Study participants were recruited at the Robert Wood Johnson Medical School Obstetrics and Gynecology ambulatory care office in New Brunswick, NJ and participated while waiting for their appointments. Our voluntary study population included English-speaking females over age 18.Primary outcomes measured were knowledge and attitudes about CMDs. Measures included individual Likert scale items and composite "stigma scores." 325 adult women were approached and 251 agreed to participate (response rate 77%). 181 of the participants completed all of the items in the pre- and posttest surveys. Results suggested increased knowledge and more positive attitudes after the intervention, corresponding to a decrease in stigma between the pre- and posttest surveys. The mean difference in stigma score on the 5pt Likert scale was 1.5 (95%CI .9 to 2.1, p .0001), and on the 3pt Likert scale was 0.9 (95%CI .3 to 1.5, p = .0028).The study suggests that resources that highlight lived experiences with peripartum CMDs as told by women themselves may be a useful educational tool. In this study, the book INSPIRE: Stories of Motherhood, told and illustrated by women who have experienced CMDs, increased participants' knowledge and resulted in more positive attitudes about these disorders.

PURPOSE: We describe the large-scale self-initiated recruitment of patients to a self-monitoring initiative for macular pathologic features during the coronavirus disease 2019 (COVID-19) pandemic. DESIGN: Observational study with retrospective analysis. PARTICIPANTS: A total of 2272 patients from the Singapore National Eye Centre (SNEC) whose visits were rescheduled over lockdown (April 13-June 1, 2020) were offered participation in a self-monitoring initiative administered by SNEC with the Alleye application (Switzerland) as the testing instrument. METHODS: This was an observational study with retrospective analysis. Demographics and characteristics were compared between those who signed up and those who did not. Similar comparisons were made between patients who complied with the initiative versus those who did not. Outcomes were tracked for 6 months starting from the commencement of lockdown. MAIN OUTCOME MEASURES: Participation and compliance rates and characteristics of patients who were more likely to participate and comply with the initiative. RESULTS: Seven hundred thirty-two patients (32%) participated in this self-monitoring initiative. Those who participated were younger (62 years of age vs. 68 years of age; P < 0.001), men, and living with family. Patients not receiving treatment and those with poorer vision in the worse-seeing eye were more likely to participate. When grouped according to diagnosis, the proportion who participated was highest for diabetic macular edema (52%), nonneovascular age-related macular degeneration (AMD; 42%), diabetic retinopathy (35%), retinal vein occlusions (18%), and neovascular AMD (15%; P < 0.001). Testing compliance rate was 43% (315/732). Patients who complied with the initiative were older, were receiving treatment, and had poorer vision in the worse-seeing eye. Trigger events occurred in 33 patients, with 5 patients having clinically verified disease progression (1.6%). CONCLUSIONS: We provide clinical data on characteristics of patients with stable retinal diseases who were offered, participated in, and complied with a self-monitoring program. The lower participation rate compared with standardized clinical studies reflects the difficulties in implementation for such initiatives in clinical settings. Despite this, self-monitoring continues to show promise in relieving clinic resources, suggesting the feasibility of scaling such programs beyond the COVID-19 pandemic.

Mitral regurgitation (MR) is common in patients with heart failure and constitutes an independent risk factor for adverse prognosis besides NYHA-class. The predictive value of dyspnea reduction after transcatheter mitral valve repair (TMVr) on outcome has not been investigated up to now.We enrolled 627 consecutive patients (47.0% female, 57.4% functional MR; median follow-up 486 days[IQR 157/961]; survival status available in 96.8%; symptoms assessed in n = 556 at baseline / n = 406 at 1 month) treated with isolated percutaneous mitral valve edge-to-edge repair in our center from 06/2010-03/2018 (exclusion of combined forms of TMVr) in a monocentric retrospective analysis. Survival was 97.6% at discharge, 73.9% after 1, 54.5% after 3, 37.6% after 5 and 21.7% after 7-years. Before TMVr, NYHA-classes III/IV were found in 89.0%. Of these, 74.7% reported symptomatic relief (reduction in NYHA-class) one month after procedure (NYHA class recorded in 406 patients at 30 days). NYHA-classes III/IV were documented in 37.2% (p 0.001) at 30 days and in 36.6% (p 0.001) at 1 year without significant changes between the follow-ups. Dyspnea reduction was accompanied by significantly improved long-term survival (1 year, 89.1 vs 71.2%, p = 0.001, 2 years: 75.5 vs 58.7%, p = 0.039) and was identified as an independent predictor for lower mortality (1-year HR for increased mortality by missing symptomatic improvement 2.94 [95%CI 1.53-5.65], p = 0.001; long-term HR 1.95 [95%CI 1.29-2.94], p = 0.001) independently in both etiologies of MR.TMVr by edge-to-edge therapy enables early and sustainable symptomatic improvement in nearly 75% of the symptomatic patients. The simple assessment of postinterventional changes in NYHA-class might serve as an independent predictor for mid- and long-term prognosis in both FMR and DMR.

For the elderly in nursery homes, a visit to the ophthalmologist is a burden, which might lead to undertreatment. We have recently started offering a novel ophthalmological service combining onsite examination and telemedical interpretation for patients with limited access to ophthalmological care. This study summarises the frequency of findings of treatable eye diseases after the first year of operation in participants who dropped out from regular ophthalmological control.Participants' clinical characteristics, frequency of service utilisation, and findings were extracted from the system and analysed.Of 1946 residents approached, 540 (27.7%; 1080 eyes) signed up for the service. A complete examination was possible in 412 persons (813 eyes) and partially possible in the remaining 128. The mean age of the examined participants mean age was 83.9 years (SD 9.7), and they were predominantly female (69.8%). The majority had a diagnosis of dementia (54.5%) and 20.2% had diabetes mellitus requiring treatment. The median care level (ranging from 0 - 12) was 7 (interquartile range 6 - 9), corresponding to a care need of 121 - 140 min/d. The mean best-corrected decimal visual acuity was 0.55 (SD 0.24). For 164 eyes (15.2%), the current spectacle correction was insufficient. An untreated cataract was present in 145 eyes (13.4%), 89 eyes (8.2%) were receiving glaucoma treatment, and 7 eyes had a decompensated glaucoma. Dry age-related macular degeneration (AMD) appeared in 276 eyes (25.6%), 12 eyes (1.1%) had wet AMD, and 24 eyes (11.0%) among patients with diabetes showed signs of diabetic retinopathy. Other pathologies were uncommon.Residents of nursery homes, who are unable to attend regular ophthalmological control, show various treatable ophthalmological conditions, including cataracts, glaucoma, and retinal pathologies. Screening with a novel telemedicine service allows for the identification of treatable conditions and careful planning and referral of patients to appropriate clinics having the necessary infrastructure for this particular population.Für ältere Menschen in Pflegeheimen ist ein Besuch beim Augenarzt eine Belastung, die zu einer Unterversorgung führen kann. Seit Kurzem bieten wir einen neuartigen augenärztlichen Dienst für Patienten mit eingeschränktem Zugang zur augenärztlichen Versorgung an, der eine Vor-Ort-Untersuchung mit telemedizinischer Interpretation kombiniert. Diese Studie fasst die Häufigkeit von behandelbaren Augenkrankheiten nach dem 1. Betriebsjahr bei Personen zusammen, die sich nicht mehr in regelmäßiger ophthalmologischer Betreuung befanden.Die klinischen Merkmale der Teilnehmer, die Häufigkeit der Inanspruchnahme des Angebotes und die Befunde wurden aus dem System extrahiert und analysiert.Von 1946 kontaktierten Bewohnern meldeten sich 540 (27,7%; 1080 Augen) für die Untersuchung an. Bei 412 Personen (813 Augen) war eine vollständige Untersuchung möglich, bei den übrigen 128 eine teilweise. Das Durchschnittsalter der untersuchten Teilnehmer betrug 83,9 Jahre (SD 9,7) und sie waren überwiegend weiblich (69,8%). Bei der Mehrheit war eine Demenz bekannt (54,5%) und 20,2% hatten einen behandlungsbedürftigen Diabetes mellitus. Die mittlere Pflegestufe (0 – 12) betrug 7 (Interquartilsbereich 6 – 9), was einem Pflegebedarf von 121 – 140 min/d entsprach. Der mittlere bestkorrigierte Dezimalvisus betrug 0,55 (SD 0,24). Bei 164 Augen (15,2%) war die aktuelle Brillenkorrektur unzureichend. Bei 145 Augen (13,4%) lag eine unbehandelte Katarakt vor, 89 Augen (8,2%) befanden sich in Glaukombehandlung und 7 Augen hatten ein dekompensiertes Glaukom. 276 Augen (25,6%) hatten eine trockene AMD, 12 Augen (1,1%) eine feuchte AMD und 24 Augen (11,0%) der Patienten mit Diabetes wiesen Anzeichen einer diabetischen Retinopathie auf. Andere Krankheitsbilder waren selten.Bei Bewohnern von Pflegeheimen, die nicht in der Lage sind, an regelmäßigen augenärztlichen Kontrollen teilzunehmen, treten verschiedene behandelbare Augenkrankheiten auf, darunter Katarakt, Glaukom und Netzhauterkrankungen. Screening mit einem neuartigen telemedizinischen Dienst ermöglicht die Identifizierung behandelbarer Erkrankungen und eine sorgfältige Planung und Überweisung der Patienten an geeignete Kliniken, die über die notwendige Infrastruktur für diese besondere Bevölkerungsgruppe verfügen.

Purpose To evaluate the predictive usefulness of quantitative imaging biomarkers, acquired automatically from OCT scans, of cross-sectional and future visual outcomes of patients with neovascular age-related macular degeneration (AMD) starting anti–vascular endothelial growth factor (VEGF) therapy. Design Retrospective cohort study. Participants Treatment-naive, first-treated eyes of patients with neovascular AMD between 2007 and 2017 at Moorfields Eye Hospital (a large, United Kingdom single center) undergoing anti-VEGF therapy. Methods Automatic segmentation was carried out by applying a deep learning segmentation algorithm to 137 379 OCT scans from 6467 eyes of 3261 patients with neovascular AMD. After applying selection criteria, 926 eyes of 926 patients were analyzed. Main Outcome Measures Correlation coefficients (R2 values) and mean absolute error (MAE) between quantitative OCT (qOCT) parameters and cross-sectional visual function, as well as the predictive value of these parameters for short-term visual change, that is, incremental visual acuity (VA) resulting from an individual injection, as well as VA at distant time points (up to 12 months after baseline). Results Visual acuity at distant time points could be predicted: R2 = 0.80 (MAE, 5.0 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and R2 = 0.7 (MAE, 7.2 ETDRS letters) after injection at 3 and at 12 months after baseline (P Conclusions Automatic segmentation enables rapid acquisition of quantitative and reproducible OCT biomarkers with potential to inform treatment decisions in the care of neovascular AMD. This furthers development of point-of-care decision-aid systems for personalized medicine.

Bachmann-Bupp syndrome (BABS) is a rare syndrome caused by gain-of-function variants in the C-terminus of ornithine decarboxylase (ODC coded by the ODC1 gene). BABS is characterized by developmental delay, macrocephaly, macrosomia, and an unusual pattern of non-congenital alopecia. Recent diagnosis of four more BABS patients provides further characterization of the phenotype of this syndrome including late-onset seizures in the oldest reported patient at 23 years of age, representing the first report for this phenotype in BABS. Neuroimaging abnormalities continue to be an inconsistent feature of the syndrome. This may be related to the yet unknown impact of ODC/polyamine dysregulation on the developing brain in this syndrome. Variants continue to cluster, providing support to a universal biochemical mechanism related to elevated ODC protein, enzyme activity, and abnormalities in polyamine levels. Recommendations for medical management can now be suggested as well as the potential for targeted molecular or metabolic testing when encountering this unique phenotype. The natural history of this syndrome will evolve with difluoromethylornithine (DFMO) therapy and raise new questions for further study and understanding.

Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF-1 used off-label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6 months of rhIGF-1 followed by 6 months of risedronate ("rhIGF-1/Risedronate") (n = 33), 12 months of risedronate ("Risedronate") (n = 33), or double placebo ("Placebo") (n = 16). Outcome measures were lumbar spine (1° endpoint: postero-anterior [PA] spine), hip, and radius aBMD by dual-energy X-ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high-resolution peripheral quantitative computed tomography (HR-pCT) (for extremity measurements) and multi-detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12 months, mean PA lumbar spine aBMD was higher in the rhIGF-1/Risedronate (p = 0.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF-1/Risedronate than the Risedronate or Placebo groups (p

Purpose To assess the preoperative objective angle alpha and angle kappa measurements of patients deciding to undergo multifocal refractive lens surgery based on a subjective positive multifocal contact lens test (MCLT). Methods Retrospective, consecutive case series. Alpha and kappa angles were measured using the iTrace aberrometer. All patients also performed a 1-week MCLT. Only patients with a positive MCLT underwent surgery. Visual outcome (UCVA) was obtained in the 1-year follow-up. We assessed the preoperative distribution of angle values within MCLT positive and negative patient groups. Results Two hundred seventeen eyes (111 patients) were included. Mean age was 56.4 years (SD 5.6) and 46.9% were female. In 71 eyes (38 patients), MCLT was positive. Of them, 12 eyes (17%) had an angle alpha and angle kappa ≥ 0.5mm. Of 146 eyes (73 patients) who refrained from surgery due to a negative MCLT, 71 eyes (48.6%) had both angles small (pn=24) with high alpha but low kappa sizes improved less (−0.31 logMAR (SD 0.13; p=0.019)). Conclusion Four out of five patients with a positive MCLT also had correspondingly small angle values. One-half of patients with low preoperative angle values refrained from surgery due to a negative MCLT result. One-year visual acuity improvement was substantial and independent from angle sizes.

ObjectivesTo investigate the association between mode of delivery and subsequent maternal sexual wellbeing.DesignProspective birth cohort study.SettingAvon (in Bristol area), UK.PopulationParticipants in the Avon Longitudinal Study of Parents and Children (ALSPAC).MethodsMode of delivery was abstracted from obstetric records and sexual wellbeing measures were collected via a self-report questionnaire. Missing data were imputed using multiple imputation, and ordinal logistic regression models for ordered categorical outcomes were adjusted for the covariates maternal age at delivery, pre-pregnancy body mass index, diabetes during pregnancy, socio-economic position, parity, depression and anxiety.Main outcome measuresSexual enjoyment and frequency at four time points postpartum (between 33 months and 18 years) and two types of sex-related pain (pain in the vagina during sex and elsewhere after sex) at 11 years postpartum.ResultsWe found no association between mode of delivery and sexual enjoyment (e.g. adjusted odds ratio [OR] 1.11, 95% confidence interval [95% CI] 0.97–1.27 at 33 months) or sexual frequency (OR 0.99, 95% CI 0.88–1.12 at 33 months). Caesarean section was associated with an increased odds of pain in the vagina during sex at 11 years postpartum as compared with vaginal delivery in the adjusted model (OR 1.74, 95% CI 1.46–2.08).ConclusionsThese findings provide no evidence supporting associations between caesarean section and sexual enjoyment or frequency. However, mode of delivery was shown to be associated with dyspareunia, which may not be limited to abdominal scarring.

Background and Objectives Being among the youngest within a school class is linked to disadvantages in various educational and mental health domains. This study aimed to investigate whether preterm born infants are particularly vulnerable to relative age effects on mental health, not previously studied. Methods We used registry data on all Norwegians born between 1989 and 1998 to compare prescription status for psychostimulants, antidepressants, hypnotics, anxiolytics, and antipsychotics per year from age 10 to 23 years (2004-2016) between exposure groups with different time of birth in the year (relative age) and different gestational age (preterm versus term). Results Of 488 470 individuals, 29 657 (6,1%) were born preterm. For term born in November/December, the adjusted odds ratio (aORs) for psychostimulant prescription compared with peers born in January/February was 1.80 (95% confidence interval [CI], 1.69–1.91) at ages 10 to 14 years, and 1.17 (95% CI, 1.08-1.27) at ages 20 to 23 years. Within preterm born, the corresponding results were 1.39 (95% CI, 1.13-1.69) and 1.34 (95% CI, 1,00–1.78) at ages 10 through 14 and 20 through 23 years, respectively. Conclusions Being relatively young within the school group was associated with increased psychostimulant prescription in the preterm as well as the term population. In contrast to term peers, the relative age effect for psychostimulant prescription seemed to persist to young adulthood for the preterm population. The results suggest that preterm individuals are vulnerable to long-term effects of relative immaturity and that they require careful consideration from both health care professionals and the school system.

Much emphasis has been placed on participant's psychological safety within genomic research studies; however, few studies have addressed parental psychological health effects associated with their child's participation in genomic studies, particularly when parents meet the threshold for clinical concern for depression. We aimed to determine if parents' depressive symptoms were associated with their child's participation in a randomized-controlled trial of newborn exome sequencing. Parents completed the Edinburgh Postnatal Depression Scale (EPDS) at baseline, immediately post-disclosure, and 3 months post-disclosure. Mothers and fathers scoring at or above thresholds for clinical concern on the EPDS, 12 and 10, respectively, indicating possible Major Depressive Disorder with Peripartum Onset, were contacted by study staff for mental health screening. Parental concerns identified in follow-up conversations were coded for themes. Forty-five parents had EPDS scores above the clinical threshold at baseline, which decreased by an average of 2.9 points immediately post-disclosure and another 1.1 points 3 months post-disclosure (both p ≤ .014). For 28 parents, EPDS scores were below the threshold for clinical concern at baseline, increased by an average of 4.7 points into the elevated range immediately post-disclosure, and decreased by 3.8 points at 3 months post-disclosure (both p < .001). Nine parents scored above thresholds only at 3 months post-disclosure after increasing an average of 5.7 points from immediately post-disclosure (p < .001). Of the 82 parents who scored above the threshold at any time point, 43 (52.4%) were reached and 30 (69.7%) of these 43 parents attributed their elevated scores to parenting stress, balancing work and family responsibilities, and/or child health concerns. Only three parents (7.0%) raised concerns about their participation in the trial, particularly their randomization to the control arm. Elevated scores on the EPDS were typically transient and parents attributed their symptomatology to life stressors in the postpartum period rather than participation in a trial of newborn exome sequencing.

Congenital syphilis (CS) is on the rise in the United States and is a growing public health concern. CS is an infection with Treponema pallidum in an infant or fetus, acquired via transplacental transmission when a pregnant woman has untreated or inadequately treated syphilis. Pregnant women with untreated syphilis are more likely to experience pregnancies complicated by stillbirth, prematurity, low birth weight, and early infant death, while their children can develop clinical manifestations of CS such as hepatosplenomegaly, bone abnormalities, developmental delays, and hearing loss. One of the ways CS can be prevented is by identifying and treating infected women during pregnancy with a benzathine penicillin G regimen that is both appropriate for the maternal stage of syphilis and initiated at least 30 days prior to delivery. In this article we discuss many of the challenges faced by both public health and healthcare systems with regards to this preventable infection, summarize missed opportunities for CS prevention, and provide practical solutions for future CS prevention strategies.

Background The current methods for calculating the ideal implant volume for breast reconstruction are based on pre- or intraoperative volume measurements of the existing breast volume and do not take into account the individual breast density of the woman. This study aims is to identify objective parameters that can help to improve the optimal implant selection. Materials and methods This retrospective analysis includes 198 breast cancer patients who underwent mastectomy. Breast densities (ACR) measured in mammography and MRI were compared with the removed breast tissue weight and volume of the implants used. In addition, the resected weight was compared directly with the implant volume to calculate a mathematical function. Results There was no significant correlation between the ACR values and the resected weights [correlation coefficient: mammography:− 0.117 (p = 0.176), MRI − 0.033 (p = 0.756)]. A negative correlation between the implant volumes and both imaging methods could be demonstrated [correlation coefficient: mammography − 0.268; p = 0.002; MRI was − 0.200 (p = 0.055)]. A highly significant correlation between the resected weights and the implant volumes (correlation coefficient 0.744; p y = 34.71 x0.39), in which any resected weight can be used for the variable x to calculate the implant volume. Conclusion We were able to show that there is a significant correlation between the resected breast tissue and the implant volume. With our novel potency function, the appropriate implant volume can be calculated for any resected weight making it easier for the surgeon to choose a fitting implant in a simple and more objective manner.

Introduction Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has repeatedly been suggested to be associated with tumorigenesis. To evaluate the role of LPCAT1 in esophageal cancer, LPCAT1 immunostaining was analyzed on a tissue microarray containing samples from esophageal cancer patients. Results In benign esophageal tissue, LPCAT1 staining was detectable in low intensities. LPCAT1 staining was increased in malignant as compared to benign esophageal tissue and was found in high intensity in 26.4% of 288 interpretable esophageal adenocarcinomas (EACs) and in 23.2% of 211 squamous cell carcinomas (ESCCs). Increased LPCAT1 staining was linked to undifferentiated tumor grading in both subtypes of EACs and ESCCs (p = 0.0273 and p = 0.0085). Conclusion However, LPCAT1 was not associated with prognosis of EAC and ESCC patients (p = 0.6838 and p = 0.4695) and thus cannot be considered a prognostic biomarker in esophageal cancers.

Modeling of retrospectively collected multi-center data of a rare disease in pediatrics is challenging because laboratory data can stem from several decades measured with different assays. Here we present a retrospective pharmacometrics (PMX) based data analysis of the rare disease congenital hypothyroidism (CH) in newborns and infants. Our overall aim is to develop a model that can be applied to optimize dosing in this pediatric patient population since suboptimal treatment of CH during the first 2 years of life is associated with a reduced intelligence quotient between 10 and 14 years. The first goal is to describe a retrospectively collected dataset consisting of 61 newborns and infants with CH up to 2 years of age. Overall, 505 measurements of free thyroxine (FT4) and 510 measurements of thyrotropin or thyroid-stimulating hormone were available from patients receiving substitution treatment with levothyroxine (LT4). The second goal is to introduce a scale/location-scale normalization method to merge available FT4 measurements since 34 different postnatal age- and assay-specific laboratory reference ranges were applied. This method takes into account the change of the distribution of FT4 values over time, i.e. a transformation from right-skewed towards normality during LT4 treatment. The third goal is to develop a practical and useful PMX model for LT4 treatment to characterize FT4 measurements, which is applicable within a clinical setting. In summary, a time-dependent normalization method and a practical PMX model are presented. Since there is no on-going or planned development of new pharmacological approaches for CH, PMX based modeling and simulation can be leveraged to personalize dosing with the goal to enhance longer-term neurological outcome in children with the rare disease CH. Supplementary Information The online version contains supplementary material available at 10.1007/s10928-021-09765-w.

Language is a potential source of predictors for suicidal thoughts and behaviors (STBs), as changes in speech characteristics, communication habits, and word choice may be indicative of increased suicide risk. We reviewed the current literature on STBs that investigated linguistic features of spoken and written language. Specifically, we performed a search in linguistic, medical, engineering, and general databases for studies that investigated linguistic features as potential predictors of STBs published in peer-reviewed journals until the end of November 2021.We included 75 studies that investigated 279,032 individuals with STBs (age = 29.53 ± 10.29, 35% females). Of those, 34 (45%) focused on lexicon, 20 (27%) on prosody, 15 (20%) on lexicon and first-person singular, four (5%) on (morpho)syntax, and two (3%) were unspecified. Suicidal thoughts were predicted by more intensifiers and superlatives, while suicidal behaviors were predicted by greater usage of pronouns, changes in the amount of verb usage, more prepend and multifunctional words, more nouns and prepositions, and fewer modifiers and numerals. A diverse field of research currently investigates linguistic predictors of STBs, and more focus is needed on their specificity for either suicidal thoughts or behaviors.

A hallmark of meiosis is chromosomal pairing, which requires telomere tethering and rotation on the nuclear envelope through microtubules, driving chromosome homology searches. Telomere pulling toward the centrosome forms the “zygotene chromosomal bouquet.” Here, we identified the “zygotene cilium” in oocytes. This cilium provides a cable system for the bouquet machinery and extends throughout the germline cyst. Using zebrafish mutants and live manipulations, we demonstrate that the cilium anchors the centrosome to counterbalance telomere pulling. The cilium is essential for bouquet and synaptonemal complex formation, oogenesis, ovarian development, and fertility. Thus, a cilium represents a conserved player in zebrafish and mouse meiosis, which sheds light on reproductive aspects in ciliopathies and suggests that cilia can control chromosomal dynamics.

Genitourinary syndrome of menopause (GSM) refers to a collection of symptoms resulting from diminished hormonal, primarily estrogenic stimulation to the vulvovaginal or lower urinary tract and may affect up to 50% of postmenopausal women. Symptoms, which are typically progressive and unlikely to resolve spontaneously, may include, but are not limited to, vulvovaginal dryness, burning or irritation, dyspareunia, or urinary symptoms of urgency, dysuria or recurrent urinary tract infection. These symptoms are typically progressive and unlikely to resolve spontaneously. Diagnosis is clinical. Telemedicine may play a role in diagnosis, initiation of treatment, and follow-up of women with GSM. Effective treatments include moisturizers and lubricants, local hormonal therapy with estrogen or dehydroepiandrosterone, and oral selective estrogen receptor agonists. Laser or radiofrequency procedures, although currently utilized, are being studied to comprehensively understand their overall effectiveness and safety. Additionally, the influence and effect of the vaginal microbiome, as well as potential of treatment via its manipulation, is being studied. We performed a literature search of PubMed, Google Scholar, and Ovid with search terms of vulvovaginal atrophy and GSM and reviewed major US Society Guidelines to create this narrative review of this topic. The literature suggests that healthcare providers can make a significant impact of the health and quality of life of women by being proactive about discussing and providing interventions for GSM. A systematic approach with consideration of current guidelines and attention to developing protocols for interventions should be employed.Video Summary:http://links.lww.com/MENO/A702.

Background Concomitant tricuspid regurgitation (TR) is a common finding in mitral regurgitation (MR). Transcatheter repair (TMVR) is a favorable treatment option in patients at elevated surgical risk. To date, evidence on long-term prognosis and the prognostic impact of TR after TMVR is limited. Methods Long-term survival data of patients undergoing isolated edge-to-edge repair from June 2010 to March 2018 (combinations with other forms of TMVR or tricuspid valve therapy excluded) were analyzed in a retrospective monocentric study. TR severity was categorized and the impact of TR on survival was analysed. Results Overall, 606 patients [46.5% female, 56.4% functional MR (FMR)] were enrolled in this study. TR at baseline was categorized severe/medium/mild/no or trace in 23.2/34.3/36.3/6.3% of the cases. At 30-day follow-up, improvement of at least one TR-grade was documented in 34.9%. Severe TR at baseline was identified as predictor of 1-year survival [65.2% vs. 77.0%, p = 0.030; HR for death 1.68 (95% CI 1.12–2.54), p = 0.013] and in FMR-patients also regarding long-term prognosis [adjusted HR for long-term mortality 1.57 (95% CI 1.00–2.45), p = 0.049]. Missing post-interventional reduction of TR severity was predictive for poor prognosis, especially in the FMR-subgroup [1-year survival: 92.9% vs. 78.3%, p = 0.025; HR for death at 1-year follow-up 3.31 (95% CI 1.15–9.58), p = 0.027]. While BNP levels decreased in both subgroups, TR reduction was associated with improved symptomatic benefit (NYHA-class-reduction 78.6 vs. 65.9%, p = 0.021). Conclusion In this large study, both, severe TR at baseline as well as missing secondary reduction were predictive for impaired long-term prognosis, especially in patients with FMR etiology. TR reduction was associated with increased symptomatic benefit. Graphic abstract

Background and Purpose: The factors associated with recovery of language domains after stroke remain uncertain. We described recovery of overall-language-ability, auditory comprehension, naming, and functional-communication across participants’ age, sex, and aphasia chronicity in a large, multilingual, international aphasia dataset. Methods: Individual participant data meta-analysis of systematically sourced aphasia datasets described overall-language ability using the Western Aphasia Battery Aphasia-Quotient; auditory comprehension by Aachen Aphasia Test (AAT) Token Test; naming by Boston Naming Test and functional-communication by AAT Spontaneous-Speech Communication subscale. Multivariable analyses regressed absolute score-changes from baseline across language domains onto covariates identified a priori in randomized controlled trials and all study types. Change-from-baseline scores were presented as estimates of means and 95% CIs. Heterogeneity was described using relative variance. Risk of bias was considered at dataset and meta-analysis level. Results: Assessments at baseline (median=43.6 weeks poststroke; interquartile range [4–165.1]) and first-follow-up (median=10 weeks from baseline; interquartile range [3–26]) were available for n=943 on overall-language ability, n=1056 on auditory comprehension, n=791 on naming and n=974 on functional-communication. Younger age ( Conclusions: Earlier intervention for poststroke aphasia was crucial to maximize language recovery across a range of language domains, although recovery continued to be observed to a lesser extent beyond 6 months poststroke.

Background Previous studies of decortication for empyema demonstrated that patient characteristics are associated with mortality, but the relationship of infectious pathogen to outcome has not been described. Our objective was to analyze the association of microbiology and antibiotic resistance with postoperative mortality after decortication for empyema. We hypothesized that bacterial pathogens, antibiotic resistance, and patient characteristics would all contribute to perioperative morbidity and mortality. Methods Patients undergoing pulmonary decortication for empyema from January 1, 2010 to October 1, 2017 were reviewed retrospectively. Cases were matched with microbiology cultures. Outcomes of interest were a composite of death, tracheostomy, initial ventilator support greater than 48 hours, or unexpected intensive care unit readmission. Antibiotic resistance was categorized as present or absent, and the number of antibiotics with resistance was counted for each patient. We describe the relationship of patient characteristics, antibiotic resistance, and microbiology to mortality. Results During the study period, 185 patients underwent decortication, 118 of whom had a diagnosis of primary empyema (63.8%). Positive culture results were present in 79 of 185 patients (43%). The most common isolate was Streptococcus, which was present in 29 of 79 (37%), followed by Staphylococcus in 19 of 79 (24%). Of 79 patients, 11 had fungal infections (13.9%). In addition, 16 of 79 patients had polymicrobial empyema (20%). Of 185 patients, 30 experienced the composite adverse outcome (16.2%). In multivariable regression, the composite adverse outcome was associated with emphysema, Candida in pleural culture, and antibiotic resistance count. Conclusions Perioperative mortality and morbidity after decortication for empyema is considerable. In this cohort, infections with increasing antibiotic resistance are associated with morbidity and mortality among patients with empyema.

The variegated squirrel bornavirus 1 (VSBV-1) is a recently discovered emerging viral pathogen which causes severe and eventually fatal encephalitis in humans after contact to exotic squirrels in private holdings and zoological gardens. Understanding the VSBV-1 epidemiology is crucial to develop, implement, and maintain surveillance strategies for the detection and control of animal and human infections. Based on a newly detected human encephalitis case in a zoological garden, epidemiological squirrel trade investigations and molecular phylogeny analyses of VSBV-1 with temporal and spatial resolution were conducted. Phylogenetic analyses indicated a recent emergence of VSBV-1 in European squirrel holdings and several animal–animal and animal–human spill-over infections. Virus phylogeny linked to squirrel trade analysis showed the introduction of a common ancestor of the known current VSBV-1 isolates into captive exotic squirrels in Germany, most likely by Prevost’s squirrels (Callosciurus prevostii). The links of the animal trade between private breeders and zoos, the likely introduction pathway of VSBV-1 into Germany, and the role of a primary animal distributor were elucidated. In addition, a seroprevalence study was performed among zoo animal caretakers from VSBV-1 affected zoos. No seropositive healthy zoo animal caretakers were found, underlining a probable high-case fatality rate of human VSBV-1 infections. This study illustrates the network and health consequences of uncontrolled wild pet trading as well as the benefits of molecular epidemiology for elucidation and future prevention of infection chains by zoonotic viruses. To respond to emerging zoonotic diseases rapidly, improved regulation and control strategies are urgently needed.

BackgroundThe small number of organ donors forces transplant centres to consider potentially suboptimal kidneys for transplantation. Eurotransplant established an algorithm for rescue allocation (RA) of kidneys repeatedly declined or not allocated within 5 h after procurement. Data on the outcomes and benefits of RA are scarce to date.MethodsWe conducted a retrospective 8-year analysis of transplant outcomes of RA offers based on our in-house criteria catalogue for acceptance and decline of organs and potential recipients.ResultsRA donors and recipients were both older compared with standard allocation (SA). RA donors more frequently had a history of hypertension, diabetes or fulfilled expanded criteria donor key parameters. RA recipients had poorer human leucocyte antigen (HLA) matches and longer cold ischaemia times (CITs). However, waiting time was shorter and delayed graft function, primary non-function and biopsy-proven rejections were comparable to SA. Five-year graft and patient survival after RA were similar to SA. In multivariate models accounting for confounding factors, graft survival and mortality after RA and SA were comparable as well.ConclusionsFacing relevant comorbidities and rapid deterioration with the risk of being removed from the waiting list, kidney transplantation after RA was identified to allow for earlier transplantation with excellent outcome. Data from this survey propose not to reject categorically organs from multimorbid donors with older age and a history of hypertension or diabetes to aim for the best possible HLA matching and to carefully calculate overall expected CIT.

Free zinc is considered to be the exchangeable and biological active form of zinc in serum, and is discussed to be a suitable biomarker for alterations in body zinc homeostasis and related diseases. Given that coronavirus disease 2019 (COVID-19) is characterized by a marked decrease in total serum zinc, and clinical data indicate that zinc status impacts the susceptibility and severity of the infection, we hypothesized that free zinc in serum might be altered in response to SARS-CoV-2 infection and may reflect disease severity. To test this hypothesis, free zinc concentrations in serum samples of survivors and nonsurvivors of COVID-19 were analyzed by fluorometric microassay. Similar to the reported total serum zinc deficit measured by total reflection X-ray fluorescence, free serum zinc in COVID-19 patients was considerably lower than that in control subjects, and surviving patients displayed significantly higher levels of free zinc than those of nonsurvivors (mean ± SD; 0.4 ± 0.2 nM vs. 0.2 ± 0.1 nM; p = 0.0004). In contrast to recovering total zinc concentrations (r = 0.706, p < 0.001) or the declining copper–zinc ratio (r = −0.646; p < 0.001), free zinc concentrations remained unaltered with time in COVID-19 nonsurvivors. Free serum zinc concentrations were particularly low in male as compared to female patients (mean ± SD; 0.4 ± 0.2 nM vs. 0.2 ± 0.1 nM; p = 0.0003). This is of particular interest, as the male sex is described as a risk factor for severe COVID-19. Overall, results indicate that depressed free serum zinc levels are associated with increased risk of death in COVID-19, suggesting that free zinc may serve as a novel prognostic marker for the severity and course of COVID-19.

Background Pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications. After careful patient selection successful pregnancies are described. Little is known about fetal outcomes and data is particularly scarce on childrens´ early development up to two years when born to kidney/−pancreas transplant recipients. Here, we analyzed maternal and fetal risk and evaluated graft function during pregnancy in transplanted women. We aimed to identify factors affecting the outcomes of mothers and their grafts during pregnancy and of children up to 2 years after delivery/ birth. Methods All consecutive pregnancies in kidney/ kidney-pancreas recipients with live-born children from 2002 to 2016 were evaluated in two transplant centers (Charité Berlin/ University Tuebingen). All data was gathered from medical records. Impact of pregnancy on obstetrical risks, graft function and fetal development was evaluated. Additionally, for the first time development of children, including physical examination and assessment of neurological function were evaluated at 12 and 24 months. Results Thirty-two pregnancies in 28 patients with a median duration of 34 gestational weeks (range, 24–38) were analyzed. 13 patients (46.4%) developed deterioration of kidney graft function > 10 ml/min during pregnancy. In majority, caesarean section was performed (75%). Twenty-five (78.1%) children were born prematurely, thereof (16%)

Ciliopathies are clinically and genetically heterogeneous diseases. We studied three patients from two independent families presenting with features of Joubert syndrome: abnormal breathing pattern during infancy, developmental delay/intellectual disability, cerebellar ataxia, molar tooth sign on magnetic resonance imaging scans, and polydactyly. We identified biallelic loss‐of‐function (LOF) variants in CBY1, segregating with the clinical features of Joubert syndrome in the families. CBY1 localizes to the distal end of the mother centriole, contributing to the formation and function of cilia. In accordance with the clinical and mutational findings in the affected individuals, we demonstrated that depletion of Cby1 in zebrafish causes ciliopathy‐related phenotypes. Levels of CBY1 transcript were found reduced in the patients compared with controls, suggesting degradation of the mutated transcript through nonsense‐mediated messenger RNA decay. Accordingly, we could detect CBY1 protein in fibroblasts from controls, but not from patients by immunofluorescence. Furthermore, we observed reduced ability to ciliate, increased ciliary length, and reduced levels of the ciliary proteins AHI1 and ARL13B in patient fibroblasts. Our data show that CBY1 LOF‐variants cause a ciliopathy with features of Joubert syndrome.

Background A lung rest strategy is recommended during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome (ARDS). However, spontaneous breathing modes are frequently used in this context. The impact of this approach may depend on the intensity of breathing efforts. The authors aimed to determine whether a low spontaneous breathing effort strategy increases lung injury, compared to a controlled near-apneic ventilation, in a porcine severe ARDS model assisted by extracorporeal membrane oxygenation. Methods Twelve female pigs were subjected to lung injury by repeated lavages, followed by 2-h injurious ventilation. Thereafter, animals were connected to venovenous extracorporeal membrane oxygenation and during the first 3 h, ventilated with near-apneic ventilation (positive end-expiratory pressure, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5/min). Then, animals were allocated into (1) near-apneic ventilation, which continued with the previous ventilatory settings; and (2) spontaneous breathing: neuromuscular blockers were stopped, sweep gas flow was decreased until regaining spontaneous efforts, and ventilation was switched to pressure support mode (pressure support, 10 cm H2O; positive end-expiratory pressure, 10 cm H2O). In both groups, sweep gas flow was adjusted to keep Paco2 between 30 and 50 mmHg. Respiratory and hemodynamic as well as electric impedance tomography data were collected. After 24 h, animals were euthanized and lungs extracted for histologic tissue analysis. Results Compared to near-apneic group, the spontaneous breathing group exhibited a higher respiratory rate (52 ± 17 vs. 5 ± 0 breaths/min; mean difference, 47; 95% CI, 34 to 59; P < 0.001), but similar tidal volume (2.3 ± 0.8 vs. 2.8 ± 0.4 ml/kg; mean difference, 0.6; 95% CI, –0.4 to 1.4; P = 0.983). Extracorporeal membrane oxygenation settings and gas exchange were similar between groups. Dorsal ventilation was higher in the spontaneous breathing group. No differences were observed regarding histologic lung injury. Conclusions In an animal model of severe ARDS supported with extracorporeal membrane oxygenation, spontaneous breathing characterized by low-intensity efforts, high respiratory rates, and very low tidal volumes did not result in increased lung injury compared to controlled near-apneic ventilation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background: Patients with chronic kidney disease (CKD) have a high risk of premature cardiovascular diseases (CVD) and show increased mortality. Pro-neurotensin (Pro-NT) was associated with metabolic diseases and predicted incident CVD and mortality. However, Pro-NT regulation in CKD and its potential role linking CKD and mortality have not been investigated, so far. Methods: In a central lab, circulating Pro-NT was quantified in three independent cohorts comprising 4715 participants (cohort 1: patients with CKD; cohort 2: general population study; and cohort 3: non-diabetic population study). Urinary Pro-NT was assessed in part of the patients from cohort 1. In a 4th independent cohort, serum Pro-NT was further related to mortality in patients with advanced CKD. Tissue-specific Nts expression was further investigated in two mouse models of diabetic CKD and compared to non-diabetic control mice. Results: Pro-NT significantly increased with deteriorating renal function (P < 0.001). In meta-analysis of cohorts 1–3, Pro-NT was significantly and independently associated with estimated glomerular filtration rate (P ≤ 0.002). Patients in the middle/high Pro-NT tertiles at baseline had a higher all-cause mortality compared to the low Pro-NT tertile (Hazard ratio: 2.11, P = 0.046). Mice with severe diabetic CKD did not show increased Nts mRNA expression in different tissues compared to control animals. Conclusions: Circulating Pro-NT is associated with impaired renal function in independent cohorts comprising 4715 subjects and is related to all-cause mortality in patients with end-stage kidney disease. Our human and rodent data are in accordance with the hypotheses that Pro-NT is eliminated by the kidneys and could potentially contribute to increased mortality observed in patients with CKD.

Small-for-gestational-age (SGA) pregnancy is a condition often leading to labor induction due to concerns about the possibility of an increased risk for fetal morbidity and mortality. In this retrospective cohort study, we try to evaluate the safety of oral misoprostol for labor induction in near-term and term pregnancies in SGA fetuses compared to dinoprostone as well as to planned primary cesarean section. Retrospective analysis of labor indution and primary cesarean section in SGA pregnancies 37 weeks and beyond in a tertiary care centre. In total, 284 consecutive patients with SGA fetuses were included. 80 recieved oral misoprostol, 85 dinoprostone as vaginal Gel and 119 were delivered by means of primary cesarean section. Primary endpoints were umbilical aterial pH and APGAR 5′. Secondary endpoints were APGAR 1′ and 10′, rates of relevant acidosis with a pH

BACKGROUND Veno-arterial extracorporeal membrane oxygenation therapy is a growing treatment modality for acute cardiorespiratory failure. Cardiac output monitoring during veno-arterial extracorporeal membrane oxygenation therapy remains challenging. This study aims to validate a new thermodilution technique during veno-arterial extracorporeal membrane oxygenation therapy using a pig model. METHODS Sixteen healthy pigs were centrally cannulated for veno-arterial extracorporeal membrane oxygenation, and precision flow probes for blood flow assessment were placed on the pulmonary artery. After chest closure, cold boluses of 0.9% saline solution were injected into the extracorporeal membrane oxygenation circuit, right atrium, and right ventricle at different extracorporeal membrane oxygenation flows (4, 3, 2, 1 l/min). Rapid response thermistors in the extracorporeal membrane oxygenation circuit and pulmonary artery recorded the temperature change. After calculating catheter constants, the distributions of injection volumes passing each circuit were assessed and enabled calculation of pulmonary blood flow. Analysis of the exponential temperature decay allowed assessment of right ventricular function. RESULTS Calculated blood flow correlated well with measured blood flow (r = 0.74, P < 0.001). Bias was -6 ml/min [95% CI ± 48 ml/min] with clinically acceptable limits of agreement (668 ml/min [95% CI ± 166 ml/min]). Percentage error varied with extracorporeal membrane oxygenation blood flow reductions, yielding an overall percentage error of 32.1% and a percentage error of 24.3% at low extracorporeal membrane oxygenation blood flows. Right ventricular ejection fraction was 17 [14 to 20.0]%. Extracorporeal membrane oxygenation flow reductions increased end-diastolic and end-systolic volumes with reductions in pulmonary vascular resistance. Central venous pressure and right ventricular ejection fractions remained unchanged. End-diastolic and end-systolic volumes correlated highly (r = 0.98, P < 0.001). CONCLUSIONS Adapted thermodilution allows reliable assessment of cardiac output and right ventricular behavior. During veno-arterial extracorporeal membrane oxygenation weaning, the right ventricle dilates even with stable function, possibly because of increased venous return. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Veno-arterial extracorporeal membrane oxygenation is an accepted rescue therapy for patients experiencing severe cardiac or pulmonary failure.Weaning from veno-arterial extracorporeal membrane oxygenation is important for determining next steps in patients' cardiopulmonary care. Assessment of right ventricular function during veno-arterial extracorporeal membrane oxygenation support and weaning is often done using echocardiography, but echocardiographic guidance provides challenges because right ventricular dimensions change with ventricular loading and may not be related to intrinsic right ventricular function. WHAT THIS ARTICLE TELLS US THAT IS NEW In 16 healthy pigs that received veno-arterial extracorporeal membrane oxygenation support via central cannulation, a novel adaptation of thermodilution cardiac output assessment provided reliable estimation of right ventricular cardiac output and right ventricular function.Future studies appear warranted to determine whether this method of modified thermodilution can be used to accurately assess right ventricular output and function during veno-arterial extracorporeal membrane oxygenation support.

Over the past 2 decades, polypharmacy has become the de-facto standard of acute treatment in psychiatry where patients with psychiatric disorders receive a multiple medication regimen. There is growing evidence for a potential link between major psychiatric disorders and inflammatory processes. Combining these two aspects aims at avoiding polypharmacy attempts among patients with inflammatory activation through alternative treatment strategies. In this study, we addressed the following questions: (1) to what extent can polypharmacy be explained through the factors “diagnosis”, “previous history”, “severity at baseline”, “age”, “gender”, and “psychiatrist in charge”; (2) what are the differences between polypharmacy and monotherapy regarding efficacy and side effect profiles; and (3) what amount of between-patient variance is explainable by the natural antibody immunoglobulin M (IgM) within each diagnostic group. This naturalistic longitudinal study was comprised of 279 patients under therapy with a clinical diagnosis of depressive (ICD-10: “F3x.x”;n = 195) or schizophrenic disorders (ICD-10: “F2x.x”;n = 84). The study protocol included (1) assessment of previous history by the SADS Syndrome Check List SSCL-16 (lifetime version); (2) repeated measurements over 5 weeks assessing the time course of improvement by the Hamilton Depression Scale HAM-D and the Positive and Negative Syndrome Scale PANSS, along with medication and unwanted side effects through the Medication and Side Effects Inventory MEDIS; and (3) the collection of blood samples from which DNA and serum were extracted. The association between inflammatory response system and psychiatric disorders was detailed by fitting multi-layer Neural Net (NN) models to the observed data (“supervised learning”). The same approach was used to set up prediction models of side effects. Our data showed that polypharmacy was omnipresent. Yet the various polypharmacy regimens had no advantage over monotherapy: we even found slightly larger baseline score reductions under monotherapy, independent of primary diagnoses and for comparable baseline severities. Most patients experienced unwanted side effects. The close link between side effects and treatment regimen was revealed by a linear model in which the mere number of drugs explained a significant (p r = 0.746 (p = 0.0004) between global schizophrenia scores and IgM levels, along with a correct prediction of response of 94.4%, thus explaining 55.7% of the observed between-patient variance. For the F3 patients, our NN model identified a 19.6% subgroup exhibiting a significant correlation ofr = 0.644 (p = 0.00003) between global depression scores and IgM levels, along a correct prediction of response of 89.6%, thus explaining 41.4% of the observed between-patient variance. Polypharmacy is omnipresent in today’s acute treatment of psychiatric disorders. Given the large proportion of patients with unwanted side effects and the strong correlation between side effects and the number of drugs, polypharmacy approaches are not equally suited for every patient. In terms of efficacy, there are no advantages of polypharmacy over monotherapy. Most notably, our study appears to have cleared the way for the reliable identification of a subgroup of patients for whom the inflammatory response system is a promising target of therapeutic intervention.

Violence against women (VAW) affects pregnancy, birthing, and puerperium. In this sense, domestic violence (DV) or intimate partner violence (IPV) may increase during pregnancy, sexual child abuse may affect the birthing process, and obstetric violence may occur during birthing. Thus, consideration of violence during pregnancy and puerperium is essential to providing optimal care for women. This implies that midwives should be able to identify women affected by VAW. Therefore, this study explored VAW as perceived by midwives in one region of Austria. Interviews with 15 midwives (mean age 38.7 years) were conducted in Tyrol, Austria, between December 2014 and December 2015. Data were analyzed with a modified version of Grounded Theory. The core category “protecting but walking on eggshells” showed the caution with which midwives approached VAW and in particular DV or IPV. Including VAW in midwifery was connected to midwives being active protectors of women in their care. This meant being an intuitive, sensible, guiding, and empowering midwife to the woman. Staying active was necessary to fulfill the protective role also with regard to DV. However, this was influenced by the visibility of the connection between VAW, pregnancy, childbirth, and puerperium. The key to including VAW and particularly DV was midwives’ professional role of actively protecting women. Neglecting DV during pregnancy, labor, and puerperium meant further silencing DV, and keeping it hidden. Considering these aspects in planning and implementing actions to prevent VAW is expected to support sustainability and motivation to ask women about all forms of violence during and after pregnancy.

Congenital syphilis is an infection with Treponema pallidum in an infant or fetus, acquired during pregnancy from a mother with untreated or inadequately treated syphilis. Congenital syphilis can cause miscarriage, stillbirth, or early infant death, and infected infants can experience lifelong physical and neurologic problems. Although timely identification and treatment of maternal syphilis during pregnancy can prevent congenital syphilis (1,2), the number of reported congenital syphilis cases in the United States increased 261% during 2013-2018, from 362 to 1,306. Among reported congenital syphilis cases during 2018, a total of 94 resulted in stillbirths or early infant deaths (3). Using 2018 national congenital syphilis surveillance data and a previously developed framework (4), CDC identified missed opportunities for congenital syphilis prevention. Nationally, the most commonly missed prevention opportunities were a lack of adequate maternal treatment despite the timely diagnosis of syphilis (30.7%) and a lack of timely prenatal care (28.2%), with variation by geographic region. Congenital syphilis prevention involves syphilis prevention for women and their partners and timely identification and treatment of pregnant women with syphilis. Preventing continued increases in congenital syphilis requires reducing barriers to family planning and prenatal care, ensuring syphilis screening at the first prenatal visit with rescreening at 28 weeks' gestation and at delivery, as indicated, and adequately treating pregnant women with syphilis (2). Congenital syphilis prevention strategies that implement tailored public health and health care interventions to address missed opportunities can have substantial public health impact.

Rationale: Patients with elevated levels of lipoprotein(a) [Lp(a)] are hallmarked by increased metabolic activity in the arterial wall on positron emission tomography/computed tomography, indicative of a proinflammatory state. Objective: We hypothesized that Lp(a) induces endothelial cell inflammation by rewiring endothelial metabolism. Methods and Results: We evaluated the impact of Lp(a) on the endothelium and describe that Lp(a), through its oxidized phospholipid content, activates arterial endothelial cells, facilitating increased transendothelial migration of monocytes. Transcriptome analysis of Lp(a)-stimulated human arterial endothelial cells revealed upregulation of inflammatory pathways comprising monocyte adhesion and migration, coinciding with increased 6-phophofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)-3–mediated glycolysis. ICAM (intercellular adhesion molecule)-1 and PFKFB3 were also found to be upregulated in carotid plaques of patients with elevated levels of Lp(a). Inhibition of PFKFB3 abolished the inflammatory signature with concomitant attenuation of transendothelial migration. Conclusions: Collectively, our findings show that Lp(a) activates the endothelium by enhancing PFKFB3-mediated glycolysis, leading to a proadhesive state, which can be reversed by inhibition of glycolysis. These findings pave the way for therapeutic agents targeting metabolism aimed at reducing inflammation in patients with cardiovascular disease.

Background: Limited research studies have been conducted on nutritional risks among female athletes. Therefore, this literature review focuses on rigorously designed studies that examined nutrition...