Impact of geographical cohorting, multidisciplinary rounding and incremental case management support on hospital length of stay and readmission rates: a propensity weighted analysis.

Hospital length of stay (LOS) in the USA has been increasing since the start of the COVID-19 pandemic, with numerous negative outcomes, including decreased quality of care, worsened patient satisfaction and negative financial impacts on hospitals. While many proposed factors contributing to prolonged LOS are challenging to modify, poor coordination of care and communication among clinical teams can be improved.Geographical cohorting of provider teams, patients and other clinical staff is proposed as a solution to prolonged LOS and readmissions. However, many studies on geographical cohorting alone have shown no significant impact on LOS or readmissions. Other potential benefits of geographical cohorting include improved quality of care, learning experience, communication, teamwork and efficiency.This paper presents a retrospective study at Duke University Hospital (DUH) on the General Medicine service, deploying a bundled intervention of geographical cohorting of patients and their care teams, twice daily multidisciplinary rounds and incremental case management support. The quality improvement study found that patients in the intervention arm had 16%-17% shorter LOS than those in the control arms, and there was a reduction in 30-day hospital readmissions compared with the concurrent control arm. Moreover, there was some evidence of improved accuracy of estimated discharge dates in the intervention arm.Based on these findings, the health system at DUH recognised the value of geographical cohorting and implemented additional geographically based medicine units with multidisciplinary rounds. Future studies will confirm the sustained impact of these care transformations on hospital throughput and patient outcomes, aiming to reduce LOS and enhance the quality of care provided to patients.

Syndromic retinitis pigmentosa caused by biallelic SCAPER frameshift variant.

PURPOSE: Mutations in the SCAPER gene have previously been reported to be a rare cause of syndromic and non-syndromic autosomal recessive retinitis pigmentosa (RP). We report a case of syndromic RP caused by a frameshift heterozygous mutation in SCAPER. Our case has a relatively mild ocular phenotype with the presence of cone involvement noted on full field electroretinogram (ffERG) without impacting central or color vision. MATERIALS AND METHODS: A 17-year-old male presented with progressive nyctalopia in both eyes. He underwent ophthalmic examination and multimodal imaging. A complete retinal degeneration panel consisting of 322 genes was used to screen for molecular causes of retinal dystrophy in this patient along with family segregation analysis. RESULTS: Fundus examination of the proband revealed mild RP phenotype with waxy pallor of optic discs, attenuated retinal arterioles, and single bone spicule like pigmentary change in the mid-periphery bilaterally. Multimodal imaging and ffERG demonstrated a picture of RP with cone dysfunction without impacting central or color vision bilaterally. Examined family members were found to be normal. The proband was found to be heterozygous for two novel frameshift pathogenic variants in SCAPER c.3781del, p. (Val1261Serfs*26), c.868_869del, p. (Glu290Serfs*7) both leading to predicted premature termination. The family members tested were found to be heterozygous for SCAPER c.868_869del, p. (Glu290Serfs*7) pathogenic variant confirming their carrier status. CONCLUSION: We report a case of a syndromic RP of previously unreported ocular phenotype associated with SCAPER pathogenic variant, which will add to the phenotypic spectrum of retinopathy and systemic features associated with pathogenic variants in SCAPER.

Protocol for a pragmatic cluster randomised controlled trial assessing the clinical effectiveness and cost-effectiveness of Electronic RIsk-assessment for CAncer for patients in general practice (ERICA).

INTRODUCTION: The UK has worse cancer outcomes than most comparable countries, with a large contribution attributed to diagnostic delay. Electronic risk assessment tools (eRATs) have been developed to identify primary care patients with a ≥2% risk of cancer using features recorded in the electronic record. METHODS AND ANALYSIS: This is a pragmatic cluster randomised controlled trial in English primary care. Individual general practices will be randomised in a 1:1 ratio to intervention (provision of eRATs for six common cancer sites) or to usual care. The primary outcome is cancer stage at diagnosis, dichotomised to stage 1 or 2 (early) or stage 3 or 4 (advanced) for these six cancers, assessed from National Cancer Registry data. Secondary outcomes include stage at diagnosis for a further six cancers without eRATs, use of urgent referral cancer pathways, total practice cancer diagnoses, routes to cancer diagnosis and 30-day and 1-year cancer survival. Economic and process evaluations will be performed along with service delivery modelling. The primary analysis explores the proportion of patients with early-stage cancer at diagnosis. The sample size calculation used an OR of 0.8 for a cancer being diagnosed at an advanced stage in the intervention arm compared with the control arm, equating to an absolute reduction of 4.8% as an incidence-weighted figure across the six cancers. This requires 530 practices overall, with the intervention active from April 2022 for 2 years. ETHICS AND DISSEMINATION: The trial has approval from London City and East Research Ethics Committee, reference number 19/LO/0615; protocol version 5.0, 9 May 2022. It is sponsored by the University of Exeter. Dissemination will be by journal publication, conferences, use of appropriate social media and direct sharing with cancer policymakers. TRIAL REGISTRATION NUMBER: ISRCTN22560297.

Workload and workflow implications associated with the use of electronic clinical decision support tools used by health professionals in general practice: a scoping review.

BACKGROUND: Electronic clinical decision support tools (eCDS) are increasingly available to assist General Practitioners (GP) with the diagnosis and management of a range of health conditions. It is unclear whether the use of eCDS tools has an impact on GP workload. This scoping review aimed to identify the available evidence on the use of eCDS tools by health professionals in general practice in relation to their impact on workload and workflow. METHODS: A scoping review was carried out using the Arksey and O'Malley methodological framework. The search strategy was developed iteratively, with three main aspects: general practice/primary care contexts, risk assessment/decision support tools, and workload-related factors. Three databases were searched in 2019, and updated in 2021, covering articles published since 2009: Medline (Ovid), HMIC (Ovid) and Web of Science (TR). Double screening was completed by two reviewers, and data extracted from included articles were analysed. RESULTS: The search resulted in 5,594 references, leading to 95 full articles, referring to 87 studies, after screening. Of these, 36 studies were based in the USA, 21 in the UK and 11 in Australia. A further 18 originated from Canada or Europe, with the remaining studies conducted in New Zealand, South Africa and Malaysia. Studies examined the use of eCDS tools and reported some findings related to their impact on workload, including on consultation duration. Most studies were qualitative and exploratory in nature, reporting health professionals' subjective perceptions of consultation duration as opposed to objectively-measured time spent using tools or consultation durations. Other workload-related findings included impacts on cognitive workload, "workflow" and dialogue with patients, and clinicians' experience of "alert fatigue". CONCLUSIONS: The published literature on the impact of eCDS tools in general practice showed that limited efforts have focused on investigating the impact of such tools on workload and workflow. To gain an understanding of this area, further research, including quantitative measurement of consultation durations, would be useful to inform the future design and implementation of eCDS tools.

Anoctamins and Calcium Signalling: An Obstacle to EGFR Targeted Therapy in Glioblastoma?

Glioblastoma is the most common form of high-grade glioma in adults and has a poor survival rate with very limited treatment options. There have been no significant advancements in glioblastoma treatment in over 30 years. Epidermal growth factor receptor is upregulated in most glioblastoma tumours and, therefore, has been a drug target in recent targeted therapy clinical trials. However, while many inhibitors and antibodies for epidermal growth factor receptor have demonstrated promising anti-tumour effects in preclinical models, they have failed to improve outcomes for glioblastoma patients in clinical trials. This is likely due to the highly plastic nature of glioblastoma tumours, which results in therapeutic resistance. Ion channels are instrumental in the development of many cancers and may regulate cellular plasticity in glioblastoma. This review will explore the potential involvement of a class of calcium-activated chloride channels called anoctamins in brain cancer. We will also discuss the integrated role of calcium channels and anoctamins in regulating calcium-mediated signalling pathways, such as epidermal growth factor signalling, to promote brain cancer cell growth and migration.

How well do Cognitive Behavioural Therapy and Behavioural Activation for depression repair anhedonia? A secondary analysis of the COBRA randomized controlled trial.

A secondary analysis of the COBRA randomized controlled trial was conducted to examine how well Cognitive Behavioural Therapy (CBT) and Behavioural Activation (BA) repair anhedonia. Patients with current major depressive disorder (N = 440) were randomized to receive BA or CBT, and anhedonia and depression outcomes were measured after acute treatment (six months) and at two further follow up intervals (12 and 18 months). Anhedonia was assessed using the Snaith Hamilton Pleasure Scale (SHAPS; a measure of consummatory pleasure). Both CBT and BA led to significant improvements in anhedonia during acute treatment, with no significant difference between treatments. Participants remained above healthy population averages of anhedonia at six months, and there was no further significant improvement in anhedonia at 12-month or 18-month follow up. Greater baseline anhedonia severity predicted reduced repair of depression symptoms and fewer depression-free days across the follow-up period in both the BA and CBT arms. The extent of anhedonia repair was less marked than the extent of depression repair across both treatment arms. These findings demonstrate that CBT and BA are similarly and only partially effective in treating anhedonia. Therefore, both therapies should be further refined or novel treatments should be developed in order better to treat anhedonia.

Potassium Ion Channels in Malignant Central Nervous System Cancers.

Malignant central nervous system (CNS) cancers are among the most difficult to treat, with low rates of survival and a high likelihood of recurrence. This is primarily due to their location within the CNS, hindering adequate drug delivery and tumour access via surgery. Furthermore, CNS cancer cells are highly plastic, an adaptive property that enables them to bypass targeted treatment strategies and develop drug resistance. Potassium ion channels have long been implicated in the progression of many cancers due to their integral role in several hallmarks of the disease. Here, we will explore this relationship further, with a focus on malignant CNS cancers, including high-grade glioma (HGG). HGG is the most lethal form of primary brain tumour in adults, with the majority of patient mortality attributed to drug-resistant secondary tumours. Hence, targeting proteins that are integral to cellular plasticity could reduce tumour recurrence, improving survival. This review summarises the role of potassium ion channels in malignant CNS cancers, specifically how they contribute to proliferation, invasion, metastasis, angiogenesis, and plasticity. We will also explore how specific modulation of these proteins may provide a novel way to overcome drug resistance and improve patient outcomes.

Mutations in phospholipase C eta-1 (PLCH1) are associated with holoprosencephaly.

BACKGROUND: Holoprosencephaly is a spectrum of developmental disorder of the embryonic forebrain in which there is failed or incomplete separation of the prosencephalon into two cerebral hemispheres. To date, dominant mutations in sonic hedgehog (SHH) pathway genes are the predominant Mendelian causes, and have marked interfamilial and intrafamilial phenotypical variabilities. METHODS: We describe two families in which offspring had holoprosencephaly spectrum and homozygous predicted-deleterious variants in phospholipase C eta-1 (PLCH1). Immunocytochemistry was used to examine the expression pattern of PLCH1 in human embryos. We used SHH as a marker of developmental stage and of early embryonic anatomy. RESULTS: In the first family, two siblings had congenital hydrocephalus, significant developmental delay and a monoventricle or fused thalami with a homozygous PLCH1 c.2065C>T, p.(Arg689*) variant. In the second family, two siblings had alobar holoprosencephaly and cyclopia with a homozygous PLCH1 c.4235delA, p.(Cys1079ValfsTer16) variant. All parents were healthy carriers, with no holoprosencephaly spectrum features. We found that the subcellular localisation of PLCH1 is cytoplasmic, but the p.(Cys1079ValfsTer16) variant was predominantly nuclear. Human embryo immunohistochemistry showed PLCH1 to be expressed in the notorcord, developing spinal cord (in a ventral to dorsal gradient), dorsal root ganglia, cerebellum and dermatomyosome, all tissues producing or responding to SHH. Furthermore, the embryonic subcellular localisation of PLCH1 was exclusively cytoplasmic, supporting protein mislocalisation contributing to the pathogenicity of the p.(Cys1079ValfsTer16) variant. CONCLUSION: Our data support the contention that PLCH1 has a role in prenatal mammalian neurodevelopment, and deleterious variants cause a clinically variable holoprosencephaly spectrum phenotype.

Heart Transplantation of a Preterm Infant With HLHS.

A 33-week gestation, 1.75-kg female infant with mitral stenosis/aortic atresia variant of hypoplastic left heart syndrome and severe ventriculo-coronary connections underwent surgical septectomy and bilateral pulmonary artery banding at five weeks of age (2.10 kg). After separation from bypass, she developed hemodynamic instability requiring venoarterial extracorporeal membrane oxygenation support. She was listed for heart transplantation and transplanted after three days of support with an oversized heart (4.7:1 donor-recipient weight ratio).

Post-injection endophthalmitis rates with reduced povidone-iodine prophylaxis in patients with self-reported iodine sensitivity.

BACKGROUND: Our objectives were (1) to report the post-injection endophthalmitis rate over 18 months, and (2) to determine any difference in the incidence of endophthalmitis in patients treated with reduced or no 5% povidone-iodine (PI) due to self-reported PI sensitivity. METHODS: We performed a retrospective cohort study of all patients who received intravitreal injections (IVIs) from January 1st, 2018 to June 26th, 2019. Information on patients' age, gender visual acuities, the number of injections, drug administered, self-reported iodine sensitivity and injection protocols were obtained from electronic and paper records. For endophthalmitis cases, vitreous culture results and treatment were also noted. Patients were divided into three cohorts based on the injection protocol used for statistical analysis. RESULTS: During the study period 22,046 IVIs were administered to 3332 eyes of 2709 patients. Intolerance to PI was reported by 2.4% of patients. The incidence of endophthalmitis was 0.02% (4/21,185) with the standard 5% PI protocol, 0.78% (6/769) with a reduced PI protocol involving fewer drops of 5% PI and chlorohexidine 0.05% for periorbital skin cleansing, and 1.09% (1/92) without any PI use. Receiving the standard PI protocol was associated with significantly lower rates of endophthalmitis compared to both the reduced PI and no PI protocols (p < 0.0001). CONCLUSIONS: Patients who opt for less or no PI use are likely at significantly increased risk of developing post-IVI endophthalmitis. It is imperative to educate, counsel and consent these patients accordingly while exploring alternative antiseptic solutions.

Chronic Pharmacological Increase of Neuronal Activity Improves Sensory-Motor Dysfunction in Spinal Muscular Atrophy Mice.

Dysfunction of neuronal circuits is an important determinant of neurodegenerative diseases. Synaptic dysfunction, death, and intrinsic activity of neurons are thought to contribute to the demise of normal behavior in the disease state. However, the interplay between these major pathogenic events during disease progression is poorly understood. Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a deficiency in the ubiquitously expressed protein SMN and is characterized by motor neuron death, skeletal muscle atrophy, as well as dysfunction and loss of both central and peripheral excitatory synapses. These disease hallmarks result in an overall reduction of neuronal activity in the spinal sensory-motor circuit. Here, we show that increasing neuronal activity by chronic treatment with the FDA-approved potassium channel blocker 4-aminopyridine (4-AP) improves motor behavior in both sexes of a severe mouse model of SMA. 4-AP restores neurotransmission and number of proprioceptive synapses and neuromuscular junctions (NMJs), while having no effects on motor neuron death. In addition, 4-AP treatment with pharmacological inhibition of p53-dependent motor neuron death results in additive effects, leading to full correction of sensory-motor circuit pathology and enhanced phenotypic benefit in SMA mice. Our in vivo study reveals that 4-AP-induced increase of neuronal activity restores synaptic connectivity and function in the sensory-motor circuit to improve the SMA motor phenotype.SIGNIFICANCE STATEMENT Spinal muscular atrophy (SMA) is a neurodegenerative disease, characterized by synaptic loss, motor neuron death, and reduced neuronal activity in spinal sensory-motor circuits. However, whether these are parallel or dependent events is unclear. We show here that long-term increase of neuronal activity by the FDA-approved drug 4-aminopyridine (4-AP) rescues the number and function of central and peripheral synapses in a SMA mouse model, resulting in an improvement of the sensory-motor circuit and motor behavior. Combinatorial treatment of pharmacological inhibition of p53, which is responsible for motor neuron death and 4-AP, results in additive beneficial effects on the sensory-motor circuit in SMA. Thus, neuronal activity restores synaptic connections and improves significantly the severe SMA phenotype.

Reliable radical stabilization energies from diffusion Monte Carlo calculations.

We assess the performance of variational (VMC) and diffusion (DMC) quantum Monte Carlo methods for calculating the radical stabilization energies of a set of 43 carbon-centered radical species. Even using simple single-determinant trial wavefunctions, both methods perform exceptionally well, with mean absolute deviations from reference values well under the chemical accuracy standard of 1 kcal/mol. In addition, the use of DMC results in a highly concentrated spread of errors, with all 43 results within chemical accuracy at the 95% confidence level. These results indicate that DMC is an extremely reliable method for calculating radical stabilization energies and could be used as a benchmark method for larger systems in future.

Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit.

By studying healthy women who do not request analgesia during their first delivery, we investigate genetic effects on labor pain. Such women have normal sensory and psychometric test results, except for significantly higher cuff pressure pain. We find an excess of heterozygotes carrying the rare allele of SNP rs140124801 in KCNG4. The rare variant KV6.4-Met419 has a dominant-negative effect and cannot modulate the voltage dependence of KV2.1 inactivation because it fails to traffic to the plasma membrane. In vivo, Kcng4 (KV6.4) expression occurs in 40% of retrograde-labeled mouse uterine sensory neurons, all of which express KV2.1, and over 90% express the nociceptor genes Trpv1 and Scn10a. In neurons overexpressing KV6.4-Met419, the voltage dependence of inactivation for KV2.1 is more depolarized compared with neurons overexpressing KV6.4. Finally, KV6.4-Met419-overexpressing neurons have a higher action potential threshold. We conclude that KV6.4 can influence human labor pain by modulating the excitability of uterine nociceptors.

Comparing international postgraduate training and healthcare context with the UK to streamline overseas GP recruitment: four case studies.

BACKGROUND: There are ambitious overseas recruitment targets to alleviate current GP shortages in the UK. GP training in European Economic Area (EEA) countries is recognised by the General Medical Council (GMC) as equivalent UK training; non-EEA GPs must obtain a Certificate of Eligibility for General Practice Registration (CEGPR), demonstrating equivalence to UK-trained GPs. The CEGPR may be a barrier to recruiting GPs from non-EEA countries. It is important to facilitate the most streamlined route into UK general practice while maintaining registration standards and patient safety. AIM: To apply a previously published mapping methodology to four non-EEA countries: South Africa, US, Canada, and New Zealand. DESIGN & SETTING: Desk-based research was undertaken. This was supplemented with stakeholder interviews. METHOD: The method consisted of: (1) a rapid review of 13 non-EEA countries using a structured mapping framework, and publicly available website content and country-based informant interviews; (2) mapping of five 'domains' of comparison between four overseas countries and the UK (healthcare context, training pathway, curriculum, assessment, and continuing professional development (CPD) and revalidation). Mapping of the domains involved desk-based research. A red, amber, or green (RAG) rating was applied to indicate the degree of alignment with the UK. RESULTS: All four countries were rated 'green'. Areas of differences that should be considered by regulatory authorities when designing streamlined CEGPR processes for these countries include: healthcare context (South Africa and US), CPD and revalidation (US, Canada, and South Africa), and assessments (New Zealand). CONCLUSION: Mapping these four non-EEA countries to the UK provides evidence of utility of the systematic method for comparing GP training between countries, and may support the UK's ambitions to recruit more GPs to alleviate UK GP workforce pressures.

Understanding why primary care doctors leave direct patient care: a systematic review of qualitative research.

BACKGROUND: UK general practitioners (GPs) are leaving direct patient care in significant numbers. We undertook a systematic review of qualitative research to identify factors affecting GPs' leaving behaviour in the workforce as part of a wider mixed methods study (ReGROUP). OBJECTIVE: To identify factors that affect GPs' decisions to leave direct patient care. METHODS: Qualitative interview-based studies were identified and their quality was assessed. A thematic analysis was performed and an explanatory model was constructed providing an overview of factors affecting UK GPs. Non-UK studies were considered separately. RESULTS: Six UK interview-based studies and one Australian interview-based study were identified. Three central dynamics that are key to understanding UK GP leaving behaviour were identified: factors associated with low job satisfaction, high job satisfaction and those linked to the doctor-patient relationship. The importance of contextual influence on job satisfaction emerged. GPs with high job satisfaction described feeling supported by good practice relationships, while GPs with poor job satisfaction described feeling overworked and unsupported with negatively impacted doctor-patient relationships. CONCLUSIONS: Many GPs report that job satisfaction directly relates to the quality of the doctor-patient relationship. Combined with changing relationships with patients and interfaces with secondary care, and the gradual sense of loss of autonomy within the workplace, many GPs report a reduction in job satisfaction. Once job satisfaction has become negatively impacted, the combined pressure of increased patient demand and workload, together with other stress factors, has left many feeling unsupported and vulnerable to burn-out and ill health, and ultimately to the decision to leave general practice.

Workforce predictive risk modelling: development of a model to identify general practices at risk of a supply-demand imbalance.

OBJECTIVE: This study aimed to develop a risk prediction model identifying general practices at risk of workforce supply-demand imbalance. DESIGN: This is a secondary analysis of routine data on general practice workforce, patient experience and registered populations (2012 to 2016), combined with a census of general practitioners' (GPs') career intentions (2016). SETTING/PARTICIPANTS: A hybrid approach was used to develop a model to predict workforce supply-demand imbalance based on practice factors using historical data (2012-2016) on all general practices in England (with over 1000 registered patients n=6398). The model was applied to current data (2016) to explore future risk for practices in South West England (n=368). PRIMARY OUTCOME MEASURE: The primary outcome was a practice being in a state of workforce supply-demand imbalance operationally defined as being in the lowest third nationally of access scores according to the General Practice Patient Survey and the highest third nationally according to list size per full-time equivalent GP (weighted to the demographic distribution of registered patients and adjusted for deprivation). RESULTS: Based on historical data, the predictive model had fair to good discriminatory ability to predict which practices faced supply-demand imbalance (area under receiver operating characteristic curve=0.755). Predictions using current data suggested that, on average, practices at highest risk of future supply-demand imbalance are currently characterised by having larger patient lists, employing more nurses, serving more deprived and younger populations, and having considerably worse patient experience ratings when compared with other practices. Incorporating findings from a survey of GP's career intentions made little difference to predictions of future supply-demand risk status when compared with expected future workforce projections based only on routinely available data on GPs' gender and age. CONCLUSIONS: It is possible to make reasonable predictions of an individual general practice's future risk of undersupply of GP workforce with respect to its patient population. However, the predictions are inherently limited by the data available.

Translating evidence into practice: recommendations by a UK expert panel on the use of aflibercept in diabetic macular oedema.

OBJECTIVES: This paper describes recommendations from a panel of UK retina experts on aflibercept in diabetic macular oedema (DMO). METHODS: A roundtable meeting was held in London, UK in March 2018. The meeting was sponsored by Bayer. RESULTS: Recommendations are based on clinical experience and level 1 evidence. Clinical experience supports the evidence base, reinforcing that aflibercept should be initiated with intensive proactive dosing at 2 mg every 4 weeks. Most panel members use six initial 4-weekly doses as in Protocol T, rather than five initial monthly doses as recommended in the Summary of product characteristics (SmPC). After intensive proactive dosing, patients with a good response (meet Protocol T 'improvement' criteria ≥5-letter improvement in visual acuity [VA] and/or ≥10% improvement in central subfield thickness [CST] from baseline) but who are not yet stable should continue with 4-weekly aflibercept until stability is reached. Patients with a good response and stability should initiate monitor-and-extend (not in line with SmPC). Those with a sub-optimal response (meet 'improvement' criteria but with additional concerns e.g. fluid worsening on macular volume map) should continue with 4-weekly aflibercept but additional treatments should be considered (aflibercept is not licensed for combination treatment). For patients with no response (no change, or meeting Protocol T 'worsening' criteria [≥5-letter decrease in VA and/or ≥ 10% increase in CST] from baseline), switching to a non-anti-vascular endothelial growth factor treatment should be considered. CONCLUSIONS: Clinical experience reinforces that, when using aflibercept in DMO, the licensed posology or Protocol T regimens achieve the best outcomes.

The Classical Complement Pathway Mediates Microglia-Dependent Remodeling of Spinal Motor Circuits during Development and in SMA.

Movement is an essential behavior requiring the assembly and refinement of spinal motor circuits. However, the mechanisms responsible for circuit refinement and synapse maintenance are poorly understood. Similarly, the molecular mechanisms by which gene mutations cause dysfunction and elimination of synapses in neurodegenerative diseases that occur during development are unknown. Here, we demonstrate that the complement protein C1q is required for the refinement of sensory-motor circuits during normal development, as well as for synaptic dysfunction and elimination in spinal muscular atrophy (SMA). C1q tags vulnerable SMA synapses, which triggers activation of the classical complement pathway leading to microglia-mediated elimination. Pharmacological inhibition of C1q or depletion of microglia rescues the number and function of synapses, conferring significant behavioral benefit in SMA mice. Thus, the classical complement pathway plays critical roles in the refinement of developing motor circuits, while its aberrant activation contributes to motor neuron disease.

Laparoscopic cholecystectomy in the Acute Care Surgery model: risk factors for complications.

BACKGROUND: The Acute Care Surgery (ACS) model developed during the last decade fuses critical care, trauma, and emergency general surgery. ACS teams commonly perform laparoscopic cholecystectomy (LC) for acute biliary disease. This study reviewed LCs performed by an ACS service focusing on risk factors for complications in the emergent setting. METHODS: All patients who underwent LC on an ACS service during a 26-month period were identified. Demographic, perioperative, and complication data were collected and analyzed with Fisher's exact test, χ2 test, and Mann-Whitney U Test. RESULTS: During the study period, 547 patients (70.2% female, mean age 46.1±18.1, mean body mass index 32.4±7.8 kg/m2) had LC performed for various acute indications. Mean surgery time was 77.9±50.2 minutes, and 5.7% of cases were performed "after hours." Rate of conversion to open procedure was 6%. Complications seen included minor bile leaks (3.8%), infection (3.8%), retained gallstones (1.1%), organ injury (1.1%), major duct injury (0.9%), and postoperative bleeding (0.9%). Statistical analysis demonstrated significant relationships between conversion, length of surgery, age, gender, and intraoperative cholangiogram with various complications. No significant relationships were detected between complications and BMI, pregnancy, attending experience, and time of operation. DISCUSSION: Although several statistically significant relationships were identified between several risk factors and complications, these findings have limited clinical significance. Factors including attending years in practice and time of the operation were not associated with increased complications. ACS services are capable of performing a high volume of LCs for emergent indications with low complication and conversion rates.-Level of evidence:IV.