Cesarean delivery is associated with lower neonatal mortality among breech pregnancies - a systematic review and meta-analysis of preterm deliveries ≤32 weeks of gestation.

OBJECTIVE: To investigate the association between actual and planned modes of delivery, neonatal mortality, and short-term outcomes among preterm pregnancies ≤32 weeks of gestation. DATA SOURCES: A systematic literature search was conducted in three main databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 16, 2022. The protocol was registered in advance in the International Prospective Register of Systematic Reviews (CRD42022377870). STUDY ELIGIBILITY CRITERIA: Eligible studies examined pregnancies ≤ 32nd gestational week. All infants received active care, and the outcomes were reported separately by different modes of delivery. Singleton and twin pregnancies at vertex and breech presentations were included. Studies that included pregnancies complicated with preeclampsia and abruptio placentae were excluded. Primary outcomes were neonatal mortality and intraventricular hemorrhage. STUDY APPRAISAL AND SYNTHESIS METHODS: Articles were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random effects model-based odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. ROBINS-I was used to assess the risk of bias. RESULTS: A total of nineteen observational studies were included involving a total of 16,042 preterm infants in this systematic review and meta-analysis. Actual cesarean delivery improves survival (odds ratio, 0.62; 95% confidence interval, 0.42 to 0.9) and decreases the incidence of intraventricular hemorrhage (odds ratio, 0.70; confidence interval, 0.57 to 0.85) compared to vaginal delivery. Planned cesarean delivery does not improve the survival of very and extremely preterm infants compared to vaginal delivery (odds ratio, 0.87; 95% confidence interval, 0.53 to 1.44). Subset analysis found significantly lower odds of death for singleton breech preterm deliveries born by both planned (odds ratio, 0.56; 95% confidence interval, 0.32 to 0.98) and actual (odds ratio, 0.34; 95% confidence interval, 0.13 to 0.88) cesarean delivery. CONCLUSION: Cesarean delivery should be the mode of delivery for preterm ≤32 weeks of gestation breech births due to the higher mortality in preterm infants born via vaginal delivery.

Sox10 Activity and the Timing of Schwann Cell Differentiation Are Controlled by a Tle4-Dependent Negative Feedback Loop.

The HMG-domain containing transcription factor Sox10 plays a crucial role in regulating Schwann cell survival and differentiation and is expressed throughout the entire Schwann cell lineage. While its importance in peripheral myelination is well established, little is known about its role in the early stages of Schwann cell development. In a search for direct target genes of Sox10 in Schwann cell precursors, the transcriptional co-repressor Tle4 was identified. At least two regions upstream of the Tle4 gene appear involved in mediating the Sox10-dependent activation. Once induced, Tle4 works in tandem with the bHLH transcriptional repressor Hes1 and exerts a dual inhibitory effect on Sox10 by preventing the Sox10 protein from transcriptionally activating maturation genes and by suppressing Sox10 expression through known enhancers of the gene. This mechanism establishes a regulatory barrier that prevents premature activation of factors involved in differentiation and myelin formation by Sox10 in immature Schwann cells. The identification of Tle4 as a critical downstream target of Sox10 sheds light on the gene regulatory network in the early phases of Schwann cell development. It unravels an elaborate regulatory circuitry that fine-tunes the timing and extent of Schwann cell differentiation and myelin gene expression.

Implementation and Process Evaluation of Alcohol Free for 40: Community-Based Programming to Reduce Alcohol Consumption.

Alcohol consumption is known to increase risk for chronic diseases and other negative health outcomes. Abstinence, even temporary, from alcohol consumption can have positive health impacts. In this article, we describe implementation and process evaluation of Ochsner Eat Fit's Alcohol Free for 40 (AFF40), an annual, 40-day voluntary alcohol abstinence challenge that takes place in six regions of Louisiana. Participants are challenged to abstain from alcohol consumption for 40 days to promote behavior change. To support participants' success, staff conduct pre and post metrics (physical and laboratory) and host community-based events to encourage replacement behaviors. Process evaluation included measures of reach, recruitment, dose, and fidelity through tracking of participant registrations, an exit survey, media analytics, and program activity logs. In 2021, 493 participants enrolled in AFF40, with 347 completing laboratory metrics and 298 completing physical metrics. Majority of exit survey respondents (74.5%) reported no alcohol consumption during the 40-day challenge and that they planned to participate in AFF40 2022 (90.9%). The Eat Fit team documented moderate engagement (48.7% of enrolled participants) in program events. Social and digital impressions and page views recorded 23,591 hits while print media resulted in over 750,000 impressions. AFF40 has shown to be highly engaging for participants and effective in supporting temporary abstinence from alcohol. Incorporating stronger methods and evaluation will enhance future program implementation and community impact. Lessons learned and implications for practice are transferable to other community-based efforts to reduce alcohol consumption.

Is transcranial magnetic stimulation as treatment for neuropathic pain in patients with spinal cord injury efficient? A systematic review.

BACKGROUND AND PURPOSE: Neuropathic pain is a clinically relevant complication in individuals with spinal cord injury (SCI). Pharmacological pain treatment is often insufficient and leads to undesirable side effects. Thus, alternative therapeutic approaches such as repetitive transcranial magnetic stimulation (rTMS) are of critical importance. We aimed to evaluate the effectiveness of rTMS in neuropathic pain secondary to SCI. METHODS: We conducted a systematic review using the PubMed/MEDLINE, EMBASE, and PsycInfo (via OVID) database up April 2021. Only randomized controlled trials were included. Results regarding the pain intensity scores were pooled using a random-effects model. RESULTS: The search identified a total of 203 potential articles. Of these, eight randomized controlled trials (RCTs) met the eligibility criteria for qualitative synthesis providing the total data of 141 patients. All studies applied high-frequency rTMS. In seven studies, rTMS was applied over the motor cortex, and in one study over the left dorsolateral prefrontal cortex. Five studies reported a significant improvement in baseline pain scores after treatment, and three studies found a significant difference between sham vs. non-sham stimulation at any time. Six RCTs were included in the quantitative synthesis and showed a significant overall reduction of pain intensity in the rTMS groups compared with the sham groups (mean difference - 0.81, 95%CI - 1.45 to - 0.17). CONCLUSIONS: Our findings indicate that high-frequency rTMS of the primary motor cortex and left dorsolateral prefrontal cortex might be promising stimulation targets for neuropathic pain in SCI.

Age-related brain structural alterations as an intermediate phenotype of psychosis.

BACKGROUND: There is only limited agreement with respect to location, directionality and functional implications of brain structural alterations observed in patients with schizophrenia. Additionally, their link to occurrence of psychotic symptoms remains unclear. A viable way of addressing these questions is to examine populations in an at-risk mental state (ARMS) before the transition to psychosis. METHODS: We tested for structural brain alterations in individuals in an ARMS compared with healthy controls and patients with first-episode psychosis (FEP) using voxel-based morphometry and measures of cortical thickness. Furthermore, we evaluated if these alterations were modified by age and whether they were linked to the observed clinical symptoms. RESULTS: Our sample included 59 individuals with ARMS, 26 healthy controls and 59 patients with FEP. We found increased grey matter volume and cortical thickness in individuals with ARMS and a similar pattern of structural alterations in patients with FEP. We further found stronger age-related reductions in grey matter volume and cortical thickness in both patients with FEP and individuals with ARMS, linking these alterations to observed clinical symptoms. LIMITATIONS: The ARMS group comprised subgroups with heterogeneous levels of psychosis risk and medication status. Furthermore, the cross-sectional nature of our study and the reduced number of older patients limit conclusions with respect to observed interactions with age. CONCLUSION: Our findings on consistent structural alterations in individuals with ARMS and patients with FEP and their link to clinical symptoms have major implications for understanding their time of occurrence and relevance to psychotic symptoms. Interactions with age found for these alterations may explain the heterogeneity of findings reported in the literature.

Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology.

BACKGROUND/AIMS: Previous diffusion tensor imaging (DTI) studies have shown microstructural changes in the brain white matter of at-risk mental state (ARMS) subjects for psychosis and patients with first-episode psychosis (FEP). However, only a few studies have been conducted in clinical high-risk samples and findings in both groups are inconsistent, in particular along the superior longitudinal fasciculus (SLF). METHODS: This DTI study used tract-based spatial statistics (TBSS) to compare fractional anisotropy (FA) and mean diffusivity (MD) between ARMS subjects, untreated and antipsychotic-treated FEP patients and healthy controls (HC) across the whole brain and the SLF. RESULTS: Compared to HC, ARMS and FEP patients showed increased FA and decreased MD in diverse regions across the whole brain including the SLF. FA in the SLF was positively correlated with positive psychotic symptoms in ARMS and FEP individuals. Furthermore, untreated but not treated FEP patients showed increased FA in the left inferior longitudinal fasciculus and right SLF. CONCLUSION: This study revealed increased FA and decreased MD in early stages of psychosis in widespread white matter tracts including the SLF. Our findings further suggest that microstructural changes in the SLF are probably related to state-dependent psychopathology.

Pituitary gland volume in at-risk mental state for psychosis: a longitudinal MRI analysis.

INTRODUCTION: Pituitary enlargement has been reported in individuals with schizophrenic psychosis or an at-risk mental state for psychosis (ARMS). In a previous study, our group could show pituitary volume increase in first episode and ARMS patients with later transition to psychosis (ARMS-T). However, there are no longitudinal studies on this issue so far. We therefore examined longitudinally whether transition to psychosis would be accompanied by a further increase of pituitary volume in antipsychotic-naïve ARMS patients. METHODS: Magnetic resonance imaging (MRI) data were acquired from 23 antipsychotic-naïve individuals with an ARMS. Ten subjects developed psychosis (ARMS-T) and 13 did not (ARMS-NT). ARMS-T were re-scanned after the onset of psychosis, and ARMS-NT were re-scanned at the end of the study period. RESULTS: There was no significant difference of the pituitary volume between ARMS-T and ARMS-NT in our sample, and there were no significant pituitary volume changes over time. Discussion Longitudinally, we could not detect any further volumetric changes in the pituitary volume with transition to psychosis. CONCLUSIONS: This, together with the result of our previous study, could indicate that the perceived level of stress in ARMS patients is constantly high from very early onward.

49-year-old woman • headache and neck pain radiating to ears and eyes • severe hypertension • Dx?

► headache and neck pain radiating to ears and eyes ► severe hypertension.

Anti-tumor necrosis factor alpha versus corticosteroids: a threefold difference in the occurence of venous thromboembolism in Inflammatory Bowel Disease - a systematic review and meta-analysis.

BACKGROUND, AIMS: Patients with inflammatory bowel disease (IBD) have a more than twofold higher risk of venous thromboembolic events (VTE) than the general population. The etiology is complex, and the role of medication is not precisely defined.We aimed to assess the effect of anti-tumor necrosis factor alpha (anti-TNFα) drugs and conventional anti-inflammatory therapy, namely corticosteroids (CS), immunomodulators (IM), and 5-aminosalicylates (5-ASA) on VTE in IBD. METHODS: A systematic search was performed in five databases on the 22nd of November 2022. We included studies reporting VTE in the distinct categories of medications, determined the proportions, and calculated the odds ratios (OR) with 95% confidence intervals (CI), using the random-effects model. The risk of bias was evaluated with the Joanna Briggs Institute Critical Appraisal Checklist and the Risk of Bias in Non-randomized Studies of Interventions tool. RESULTS: The quantitative analysis included 16 observational studies, with data from 91,322 IBD patients. Patients receiving anti-TNFα medication had significantly less VTE (proportion: 0.05, CI: 0.02-0.10), than patients treated with CS (proportion: 0.16, CI: 0.07-0.32), with OR=0.42 (CI: 0.25-0.71). IMs resulted in similar proportions of VTE compared with biologics (0.05, CI: 0.03-0.10), with OR=0.94 (CI: 0.67-1.33). The proportion of patients receiving 5-ASA having VTE was 0.09 (CI: 0.04-0.20), with OR=1.00 (CI: 0.61-1.62). CONCLUSIONS: Biologics should be preferred over corticosteroids in cases of severe flare-ups and multiple VTE risk factors, as they are associated with reduced odds of these complications. Further studies are needed to validate our data.

Data accuracy, consistency and completeness of the national Swiss cystic fibrosis patient registry: Lessons from an ECFSPR data quality project.

BACKGROUND: Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research. METHODS: All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed. RESULTS: The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with <5 % for almost all variables. A considerable number of missing source data occurred for CFTR variants. Availability of ICs varied largely between centers (10 centers had >5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved. CONCLUSIONS: Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research.

Diagnostic precision and identification of rare diseases is dependent on distance of residence relative to tertiary medical facilities.

BACKGROUND: Diagnostic precision and the identification of rare diseases is a daily challenge, which needs specialized expertise. We hypothesized, that there is a correlation between the distance of residence to the next tertiary medical facility with highly specialized care and the diagnostic precision, especially for rare diseases. RESULTS: Using a nation-wide hospitalization database, we found a negative association between diagnostic diversity and travel time to the next tertiary referral hospital when including all cases throughout the overall International Classification of Diseases version 10 German Modification (ICD-10-GM) diagnosis codes. This was paralleled with a negative association of standardized incidence rates in all groups of rare diseases defined by the Orphanet rare disease nomenclature, except for rare teratologic and rare allergic diseases. CONCLUSION: Our findings indicate a higher risk of being mis-, under- or late diagnosed especially in rare diseases when living more distant to a tertiary medical facility. Greater distance to the next tertiary medical facility basically increases the chance for hospitalization in a non-comprehensive regional hospital with less diagnostic capacity, and, thus, impacts on adapted health care access. Therefore, solutions for overcoming the distance to specialized care as an indicator of health care access are a major goal in the future.

Record Linkage in Clinical Cancer Registration: Experiences and Findings from Lower Saxony.

In cancer registries, record linkage procedures are used to link records of the same patient from different health care providers. In the Clinical Cancer Registry of Lower Saxony, a multi-level combination of exact assignment using the statutory health insurance number and a probabilistic procedure with control numbers and address data is applied. The procedure implemented in the register application assigns the incoming messages in this way as far as possible automatically. The aim of the observation carried out was to check the efficiency of the match variables and threshold values used, above which manual assignment is required. Weak points were identified and approaches to solutions were developed.

Does Hippocampal Volume Predict Transition to Psychosis in a High-Risk Group? A Meta-Analysis.

Schizophrenia has a prodromal phase of several years in most patients, making it possible to identify patients at clinical high risk (CHR) for developing the disorder. So far, these individuals are identified based on clinical criteria alone, and there is no reliable biomarker for predicting the transition to psychosis. It is well-established that reductions in brain volume, especially in the hippocampus, are associated with schizophrenia. Therefore, hippocampal volume may serve as a biomarker for psychosis. Several studies have already investigated hippocampal volume in CHR groups. Based on these studies, the present meta-analysis compares the baseline left and right hippocampal volume of CHR patients who developed a psychosis with that of CHR patients without such a transition. Our results show no statistically significant effect of the hippocampal volume on the transition risk for psychosis.

Renal Sympathetic Denervation by Image-Guided Percutaneous Ethanol Injection - Histopathologic Characteristics, Efficacy and Safety.

PURPOSE: Evaluation of the efficacy and safety of chemical renal denervation by image-guided periarterial ethanol injection in pigs with emphasis on histopathological characteristics. MATERIALS AND METHODS: Unilateral renal periarterial ethanol injection under general anesthesia was performed in 16 animals with the contralateral kidney serving as the control. All interventions were performed in an open MRI system under real-time multiplanar guidance. In 10 pigs an ethanol-carbostesin contrast agent mixture was injected with amounts of 5 ml (6 animals, group I) and 10 ml (4 animals, group II). 6 pigs (group III) were treated with 10 ml of an ethanol-polyacrylic (2 %) mixture. Four weeks after treatment, all animals underwent MRI including MRA. After euthanasia, macroscopic and histologic examination of the kidneys, renal arteries and periarterial tissue was performed to assess nerve injury and potential side effects. Furthermore, the norepinephrine concentration (RTNEC) in the renal tissue was determined as a surrogate parameter of efficacy. RESULTS: Histologic signs of nerval degeneration with various degrees of severity and circumferential distribution were found in all groups. Injury depths ranged up to 7.6 mm. In groups II and III the nerve count was significantly lower on the treated side. Renal artery stenosis was not observed in any pig. In all pigs of group II treatment resulted in neural degeneration with a mean RTNEC reduction of 53 % (p < 0.02). In groups I and III significant changes in RTNEC were not observed. CONCLUSION: Image-guided percutaneous periarterial ethanol injection was efficient and safe for renal denervation. The detected variations in histologic outcome underlined the importance of the preclinical optimization of the technique in order to maximize treatment effects in humans. KEY POINTS: · Renal denervation by percutaneous periarterial ethanol injection is an effective and potentially safe procedure.. · The percutaneous approach is less prone to anatomical and procedural limitations compared to catheter-based procedures.. · The achievable nerve injury depth lies beyond those of current RFA-probes.. · Efficacy depends on amount, concentration, viscosity and periarterial distribution of the ethanol-mixture.. · Establishing an optimal balance between these parameters is mandatory for a maximum treatment effect at minimum risk for sensitive adjacent structures.. CITATION FORMAT: · Freyhardt P, Haage P, Walter A et al. Renal Sympathetic Denervation by Image-Guided Percutaneous Ethanol Injection - Histopathologic Characteristics, Efficacy and Safety. Fortschr Röntgenstr 2020; 192: 549 - 560.

[Pharmaceutical care for a patient with ischemic stroke]. / Pharmazeutische Betreuung eines Patienten mit zerebraler Ischämie im stationären Bereich.

A 61-year-old patient with a sudden numbness of the right arm and hand and signs of amnestic aphasia is admitted to the stroke unit with the diagnosis of an acute ischemic stroke for systemic thrombolysis. Based on a case-report, drug-related problems are discussed according to the SOAP scheme. Aspects of pharmaceutical care such as counselling by a pharmacist about secondary prevention, discharge information and a pharmaceutical care plan in the community pharmacy are described.

Duration of untreated psychosis/illness and brain volume changes in early psychosis.

The time period during which patients manifest psychotic or unspecific symptoms prior to treatment (duration of untreated psychosis, DUP, and the duration of untreated illness, DUI) has been found to be moderately associated with poor clinical and social outcome. Equivocal evidence exists of an association between DUP/DUI and structural brain abnormalities, such as reduced hippocampus volume (HV), pituitary volume (PV) and grey matter volume (GMV). Thus, the goal of the present work was to examine if DUP and DUI are associated with abnormalities in HV, PV and GMV. Using a region of interest (ROI) based approach, we present data of 39 patients from the Basel FePsy (Früherkennung von Psychosen, early detection of psychosis) study for which information about DUP, DUI and HV, PV and GMV data could be obtained. Twenty-three of them were first episode psychosis (FEP) and 16 at-risk mental state (ARMS) patients who later made the transition to frank psychosis. In unadjusted analyses, we found a significant positive correlation between DUP and PV in FEP patients. However, when adjusted for covariates, we found no significant correlation between DUP or DUI and HV, PV or GMV anymore. There only was a trend for decreasing GMV with increasing DUI in FEP. Our results do not comprehensively support the hypothesis of a "toxic" effect of the pathogenic mechanism underlying untreated psychosis on brain structure. If there is any effect, it might rather occur very early in the disease process, during which patients experience only unspecific symptoms.

Calcium Imaging in Pluripotent Stem Cell-Derived Cardiac Myocytes.

The possibility to generate cardiomyocytes (CMs) from disease-specific induced pluripotent stem cells (iPSCs) is a powerful tool for the investigation of various cardiac diseases in vitro. The pathological course of various cardiac conditions, causatively heterogeneous, often converges into disturbed cellular Ca(2+) cycling. The gigantic Ca(2+) channel of the intracellular Ca(2+) store of CMs, the ryanodine receptor type 2 (RyR2), controls Ca(2+) release and therefore plays a crucial role in Ca(2+) cycling of CMs. In the present protocol we describe ways to measure and analyze global as well as local cellular Ca(2+) release events in CMs derived from a patient carrying a CPVT-causing RyR2 mutation.

Counter striking psychosis: Commercial video games as potential treatment in schizophrenia? A systematic review of neuroimaging studies.

Schizophrenia is a severe, chronic, and strongly disabling neuropsychiatric disorder, characterized by cognitive decline, positive and negative symptoms. Positive symptoms respond well to antipsychotic medication and psycho-social interventions, in contrast to negative symptoms and neurocognitive impairments. Cognitive deficits have been linked to a poorer outcome and hence specific cognitive remediation therapies have been proposed. Their effectiveness is nowadays approved and neurobiological correlates have been reconfirmed by brain imaging studies. Interestingly, recent MRI work showed that commercial video games modified similar brain areas as these specialized training programs. If gray matter increases and functional brain modulations would translate in better cognitive and every day functioning, commercial video game training could be an enjoyable and economically interesting treatment option for patients with neuropsychiatric disorders. This systematic review summarizes advances in the area with emphasis on imaging studies dealing with brain changes upon video game training and contrasts them to conventional cognitive remediation. Moreover, we discuss potential challenges therapeutic video game development and research would have to face in future treatment of schizophrenia.

Hippocampal volume in subjects at clinical high-risk for psychosis: A systematic review and meta-analysis.

Several magnetic resonance imaging studies have reported reductions in hippocampal volume in patients with psychosis. It is unclear whether structural abnormalities predate illness onset. We conducted a detailed, systematic literature search for studies reporting hippocampal volume in subjects with clinical high-risk, compared to healthy controls. The overall sample size comprised 1429 subjects. Meta-analysis revealed no difference for left, but a small, albeit significant, difference for right hippocampal volume, such that clinical high-risk patients had slightly smaller hippocampal volume than healthy controls (g=0.24, p=0.0418). Meta-regression indicated a moderating effect of manual tracing approach, due to one outlying site. The small difference on the right side did not remain significant (g=0.14, 95%CI=[-0.03-0.32], p=0.11) after removal of this outlier. This meta-analysis suggests that there is no reduction in hippocampal volume before transition to psychosis and hippocampal volume cannot be used as a biomarker in clinical high-risk individuals.

Gene profiling of embryonic skeletal muscle lacking type I ryanodine receptor Ca(2+) release channel.

In mature skeletal muscle, the intracellular Ca(2+) concentration rises dramatically upon membrane depolarization, constituting the link between excitation and contraction. This process requires Ca(2+) release from the sarcoplasmic reticulum via the type 1 ryanodine receptor (RYR1). However, RYR1's potential roles in muscle development remain obscure. We used an established RyR1- null mouse model, dyspedic, to investigate the effects of the absence of a functional RYR1 and, consequently, the lack of RyR1-mediated Ca(2+) signaling, during embryogenesis. Homozygous dyspedic mice die after birth and display small limbs and abnormal skeletal muscle organization. Skeletal muscles from front and hind limbs of dyspedic fetuses (day E18.5) were subjected to microarray analyses, revealing 318 differentially expressed genes. We observed altered expression of multiple transcription factors and members of key signaling pathways. Differential regulation was also observed for genes encoding contractile as well as muscle-specific structural proteins. Additional qRT-PCR analysis revealed altered mRNA levels of the canonical muscle regulatory factors Six1, Six4, Pax7, MyoD, MyoG and MRF4 in mutant muscle, which is in line with the severe developmental retardation seen in dyspedic muscle histology analyses. Taken together, these findings suggest an important non-contractile role of RyR1 or RYR1-mediated Ca(2+) signaling during muscle organ development.