Long-term Anatomical and Functional Results of Robot-Assisted Pelvic Floor Surgery for the Management of Multicompartment Prolapse:A Prospective Study

BACKGROUND: Long-term data on robot-assisted sacrocolporectopexy for the treatment of multicompartment pelvic organ prolapse are scarce. With the rising prevalence of prolapse and increasing surgical repair, it is essential to evaluate long-term results. OBJECTIVE: This study aimed to evaluate long-term functional and anatomic outcomes after sacrocolporectopexy. DESIGN: This is a prospective, observational cohort study. SETTINGS: This study was conducted at a teaching hospital with tertiary referral function for patients with gynecological/rectal prolapse. PATIENTS: All patients undergoing robot-assisted sacrocolporectopexy from 2011 to 2012 were included. INTERVENTION: Robot-assisted sacrocolporectopexy was performed. MAIN OUTCOME MEASURES: The primary outcome was the anatomic cure rate after 1 and 4 years, defined as simplified pelvic organ prolapse quantification stage 1 vaginal apical prolapse and no external rectal prolapse or internal rectal prolapse present. Kaplan-Meier curves were used for determination of recurrence-free intervals. Secondary outcomes were functional pelvic floor symptoms (symptoms of bulge, obstructed defecation, fecal incontinence, urogenital distress inventory) and quality of life (Pelvic Floor Impact Questionnaire). RESULTS: Fifty-three patients were included. After 12 and 48 months, the recurrence-free intervals based on Kaplan-Meier estimates were 100% and 90%. In total, there were 10 recurrences: 2 apical and 8 internal rectal prolapses. Symptoms of bulge (94%-12%; p < 0.0005), fecal incontinence (62%-32%; p < 0.0005), obstructed defecation (59%-24%; p = 0.008), and median Pelvic Floor Impact Questionnaire scores (124-5; p = 0.022) improved significantly at final follow-up. Median urogenital distress inventory scores showed improvement after 1 year (30-13; p = 0.021). LIMITATIONS: This was an observational, single-center study with selective postoperative imaging. CONCLUSIONS: Ninety percent of patients were recurrence free 48 months after robot-assisted sacrocolporectopexy. Symptoms of vaginal bulge, quality of life, constipation, and fecal incontinence improved significantly. However, a subgroup of patients showed persistent bowel complaints that underlie the complexity of multicompartment prolapse. See Video Abstract at http://links.lww.com/DCR/B265

Cytomegalovirus is associated with depression and anxiety in older adults

Infection with cytomegalovirus (CMV), a β-herpesvirus, is common within the population. Although asymptomatic, infection is associated with increased serum concentrations of cytokines such as TNFα and IL-6, which are also related to mood and wellbeing. The present study examined whether infection with CMV was associated with mood in a community-based sample of olderadults. Blood samples and scores on the General Health Questionnaire were available for 137 participants. Serum was analysed for the presence of CMV-specific IgG and the antibody titre was used as an indirect measure of viral load. The majority of the participants (66%) were CMV-seropositive and seropositive status was not associated with psychological morbidity. However, within the CMV-positive group, individuals with higher CMV-specific antibody titres were more likely to be depressed, anxious, and suffer more overall psychological morbidity. This association could be mediated by the impact of affect-moderating cytokines secreted through the CMV-specific immune response.\ud \u

Long-term mesh erosion rate following abdominal robotic reconstructive pelvic floor surgery:a prospective study and overview of the literature

Introduction and hypothesis: The use of synthetic mesh in transvaginal pelvic floor surgery has been subject to debate internationally. Although mesh erosion appears to be less associated with an abdominal approach, the long-term outcome has not been studied intensively. This study was set up to determine the long-term mesh erosion rate following abdominal pelvic reconstructive surgery. Methods: A prospective, observational cohort study was conducted in a tertiary care setting. All consecutive female patients who underwent robot-assisted laparoscopic sacrocolpopexy and sacrocolporectopexy in 2011 and 2012 were included. Primary outcome was mesh erosion. Preoperative and postoperative evaluation (6 weeks, 1 year, 5 years) with a clinical examination and questionnaire regarding pelvic floor symptoms was performed. Mesh-related complications were assessed using a transparent vaginal speculum, proctoscopy, and digital vaginal and rectal examination. Kaplan–Meier estimates were calculated for mesh erosion. A review of the literature on mesh exposure after minimally invasive sacrocolpopexy was performed (≥12 months’ follow-up). Results: Ninety-six of the 130 patients included (73.8%) were clinically examined. Median follow-up time was 48.1 months (range 36.0–62.1). Three mesh erosions were diagnosed (3.1%; Kaplan–Meier 4.9%, 95% confidence interval 0–11.0): one bladder erosion for which mesh resection and an omental patch interposition were performed, and two asymptomatic vaginal erosions (at 42.7 and 42.3 months) treated with estrogen cream in one. Additionally, 22 patients responded solely by questionnaire and/or telephone; none reported mesh-related complaints. The literature, mostly based on retrospective studies, described a median mesh erosion rate of 1.9% (range 0–13.3%). Conclusions: The long-term rate of mesh erosion following an abdominally placed synthetic graft is low

GATA transcription factors in testicular adrenal rest tumours

Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8)). We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively), while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes). Incubation of adrenocortical cells (H295RA) with ACTH, however, did not induce GATA expression in vitro Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation

New clinical prediction model for early recognition of sepsis in adult primary care patients:a prospective diagnostic cohort study of development and external validation

Background Recognising patients who need immediate hospital treatment for sepsis while simultaneously limiting unnecessary referrals is challenging for GPs.Aim To develop and validate a sepsis prediction model for adult patients in primary care.Design and setting This was a prospective cohort study in four out-of-hours primary care services in the Netherlands, conducted between June 2018 and March 2020.Method Adult patients who were acutely ill and received home visits were included. A total of nine clinical variables were selected as candidate predictors, next to the biomarkers C-reactive protein, procalcitonin, and lactate. The primary endpoint was sepsis within 72 hours of inclusion, as established by an expert panel. Multivariable logistic regression with backwards selection was used to design an optimal model with continuous clinical variables. The added value of the biomarkers was evaluated. Subsequently, a simple model using single cut-off points of continuous variables was developed and externally validated in two emergency department populations.Results A total of 357 patients were included with a median age of 80 years (interquartile range 71–86), of which 151 (42%) were diagnosed with sepsis. A model based on a simple count of one point for each of six variables (aged &gt;65 years; temperature &gt;38°C; systolic blood pressure ≤110 mmHg; heart rate &gt;110/min; saturation ≤95%; and altered mental status) had good discrimination and calibration (C-statistic of 0.80 [95% confidence interval = 0.75 to 0.84]; Brier score 0.175). Biomarkers did not improve the performance of the model and were therefore not included. The model was robust during external validation.Conclusion Based on this study’s GP out-of-hours population, a simple model can accurately predict sepsis in acutely ill adult patients using readily available clinical parameters

Predicting sepsis-related mortality and ICU admissions from telephone triage information of patients presenting to out-of-hours GP cooperatives with acute infections: A cohort study of linked routine care databases

BACKGROUND: General practitioners (GPs) often assess patients with acute infections. It is challenging for GPs to recognize patients needing immediate hospital referral for sepsis while avoiding unnecessary referrals. This study aimed to predict adverse sepsis-related outcomes from telephone triage information of patients presenting to out-of-hours GP cooperatives. METHODS: A retrospective cohort study using linked routine care databases from out-of-hours GP cooperatives, general practices, hospitals and mortality registration. We included adult patients with complaints possibly related to an acute infection, who were assessed (clinic consultation or home visit) by a GP from a GP cooperative between 2017-2019. We used telephone triage information to derive a risk prediction model for sepsis-related adverse outcome (infection-related ICU admission within seven days or infection-related death within 30 days) using logistic regression, random forest, and neural network machine learning techniques. Data from 2017 and 2018 were used for derivation and from 2019 for validation. RESULTS: We included 155,486 patients (median age of 51 years; 59% females) in the analyses. The strongest predictors for sepsis-related adverse outcome were age, type of contact (home visit or clinic consultation), patients considered ABCD unstable during triage, and the entry complaints"general malaise", "shortness of breath" and "fever". The multivariable logistic regression model resulted in a C-statistic of 0.89 (95% CI 0.88-0.90) with good calibration. Machine learning models performed similarly to the logistic regression model. A "sepsis alert" based on a predicted probability >1% resulted in a sensitivity of 82% and a positive predictive value of 4.5%. However, most events occurred in patients receiving home visits, and model performance was substantially worse in this subgroup (C-statistic 0.70). CONCLUSION: Several patient characteristics identified during telephone triage of patients presenting to out-of-hours GP cooperatives were associated with sepsis-related adverse outcomes. Still, on a patient level, predictions were not sufficiently accurate for clinical purposes

Acetylsalicylic acid as an adjuvant therapy for schizophrenia

BACKGROUND: Findings from both epidemiological and basic research point to the possibility that NSAIDS impede the deterioration in schizophrenia. METHODS: To study the efficacy of acetylsalicylic acid we will perform a randomized placebo controlled double-blind add-on trial of 80 inpatients and outpatients with schizophrenia, schizophreniform or schizoaffective disorder. Patients will be 1:1 randomized to either 3 months 1000 mg acetylsalicylic acid per day or 3 months placebo, in addition to their regular antipsychotic treatment. All patients will receive pantoprazole treatment for gastroprotection. The outcomes of this study are 3-month change in psychotic and negative symptom severity, cognitive function, and several immunological parameters. This trial may (1) yield a new (adjuvant) therapy for schizophrenia and (2) add to the knowledge on the pathogenesis of this major psychiatric disorder

Prognostication using SpO(2)/FiO(2) in invasively ventilated ICU patients with ARDS due to COVID-19-Insights from the PRoVENT-COVID study

Background: The SpO(2)/FiO(2) is a useful oxygenation parameter with prognostic capacity in patients with ARDS. We investigated the prognostic capacity of SpO(2)/FiO(2) for mortality in patients with ARDS due to COVID-19. Methods: This was a post-hoc analysis of a national multicenter cohort study in invasively ventilated patients with ARDS due to COVID-19. The primary endpoint was 28-day mortality. Results: In 869 invasively ventilated patients, 28-day mortality was 30.1%. The SpO(2)/FiO(2) on day 1 had no prognostic value. The SpO(2)/FiO(2) on day 2 and day 3 had prognostic capacity for death, with the best cut-offs being 179 and 199, respectively. Both SpO(2)/FiO(2) on day 2 (OR, 0.66 [95%-CI 0.46-0.96]) and on day 3 (OR, 0.70 [95%-CI 0.51-0.96]) were associated with 28-day mortality in a model corrected for age, pH, lactate levels and kidney dysfunction (AUROC 0.78 [0.76-0.79]). The measured PaO2/FiO(2) and the PaO2/FiO(2) calculated from SpO(2)/FiO(2) were strongly correlated (Spearman's r = 0.79). Conclusions: In this cohort of patients with ARDS due to COVID-19, the SpO(2)/FiO(2) on day 2 and day 3 are independently associated with and have prognostic capacity for 28-day mortality. The SpO(2)/FiO(2) is a useful metric for risk stratification in invasively ventilated COVID-19 patients. (C) 2021 The Authors. Published by Elsevier Inc

Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: A centre randomised, cross-over, open-label study in the Netherlands

Objective: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia. Design: Centre randomised, open-label, crossover, 'real-life' study. Setting: 15 Dutch hospitals. Patients: Adult medical and post-surgical ICU patients with anticipated short-term (2-3 days) MV. Interventions: Patient cohorts were randomised to remifentanil-based regimen (n = 96) with propofol as required, for a maximum of 10 days, or to conventional regimens (n = 109) of propofol, midazolam or lorazepam combined with fentanyl or morphine. Measurements and main results: Outcomes were weaning time, duration of MV, ICU-LOS, sedation- and analgesia levels, intensivist/ICU nurse satisfaction, adverse events, mean arterial pressure, heart rate. Median duration of ventilation (MV) was 5.1 days with conventional treatment versus 3.9 days with remifentanil (NS). The remifentanil-based regimen reduced median weaning time by 18.9 h (P = 0.0001). Median ICU-LOS was 7.9 days versus 5.9 days, respectively (NS). However, the treatment effects on duration of MV and ICU stay were time-dependent: patients were almost twice as likely to be extubated (P = 0.018) and discharged from the ICU (P = 0.05) on day 1-3. Propofol doses were reduced by 20% (P = 0.05). Remifentanil also improved sedation-agitation scores (P < 0.0001) and intensivist/ICU nurse satisfaction (P < 0.0001). All other outcomes were comparable. Conclusions: In patients with an expected short-term duration of MV, remifentanil significantly improves sedation and agitation levels and reduces weaning time. This contributes to a shorter duration of MV and ICU-LOS