Hereditary C1q Deficiency is Associated with Type 1 Interferon-Pathway Activation and a High Risk of Central Nervous System Inflammation.

Hereditary C1q deficiency (C1QDef) is a rare monogenic disorder leading to defective complement pathway activation and systemic lupus erythematosus (SLE)-like manifestations. The link between impairment of the complement cascade and autoimmunity remains incompletely understood. Here, we assessed type 1 interferon pathway activation in patients with C1QDef. Twelve patients with genetically confirmed C1QDef were recruited through an international collaboration. Clinical, biological and radiological data were collected retrospectively. The expression of a standardized panel of interferon stimulated genes (ISGs) in peripheral blood was measured, and the level of interferon alpha (IFNα) protein in cerebrospinal fluid (CSF) determined using SIMOA technology. Central nervous system (encompassing basal ganglia calcification, encephalitis, vasculitis, chronic pachymeningitis), mucocutaneous and renal involvement were present, respectively, in 10, 11 and 2 of 12 patients, and severe infections recorded in 2/12 patients. Elevated ISG expression was observed in all patients tested (n = 10/10), and serum and CSF IFNα elevated in 2/2 patients. Three patients were treated with Janus-kinase inhibitors (JAKi), with variable outcome; one displaying an apparently favourable response in respect of cutaneous and neurological features, and two others experiencing persistent disease despite JAKi therapy. To our knowledge, we report the largest original series of genetically confirmed C1QDef yet described. Additionally, we present a review of all previously described genetically confirmed cases of C1QDef. Overall, individuals with C1QDef demonstrate many characteristics of recognized monogenic interferonopathies: particularly, cutaneous involvement (malar rash, acral vasculitic/papular rash, chilblains), SLE-like disease, basal ganglia calcification, increased expression of ISGs in peripheral blood, and elevated levels of CSF IFNα.

Implementation of Cardiometabolic Centers and Training Programs.

PURPOSE OF REVIEW: Type 2 diabetes is frequently accompanied by obesity, nonalcoholic fatty liver disease, chronic kidney disease, and cardiovascular disease, which collectively contribute to the high burden of cardiometabolic disease. This review discusses cardiometabolic disease management, strategies to implement cardiometabolic centers to deliver care, and dedicated programs to train the next generation of cardiometabolic experts. RECENT FINDINGS: Sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid receptor antagonist have demonstrated beneficial effects across cardiometabolic conditions. However, utilization of effective pharmacotherapies is low in clinical practice, in part due to clinical inertia and traditional sharp delineation in clinical responsibilities of specialists. Multidisciplinary clinics and population-health models can provide comprehensive care but require investment in physical and information technology infrastructure as well as in training and accreditation. Post-internal medicine residency cardiometabolic health training programs have been proposed. Implementing cardiometabolic centers in health systems involves reshaping current practices. Training programs focused on cardiometabolic health are needed to address the growing burden of disease and specific training needs in this ever-expanding area.

Antibullying Interventions in Schools: Assessing the Evidence Base.

OBJECTIVE: This systematic review used established rating criteria to describe the level of evidence for interventions aimed at preventing or reducing bullying perpetration and victimization in schools, synthesized the evidence for students from racially and ethnically diverse backgrounds, and reviewed the literature for available information to conduct an economic analysis of the interventions. METHODS: Major databases, gray literature, and evidence-base registries were searched to identify studies published from 2008 through 2022. The authors rated antibullying intervention models as having high, moderate, or low evidence depending on the number and rigor of studies with positive findings. RESULTS: Overall, 80 articles reporting on 71 original research studies describing a total of 48 antibullying interventions met the inclusion criteria for this review. Two schoolwide interventions received a high-evidence rating: the KiVa (Kiusaamista Vastaan) Antibullying Program and the Friendly Schools program. Multilevel interventions with components at the levels of school, classroom, and individual student most consistently showed strong evidence for reducing bullying behavior in elementary and middle school grades. Four interventions yielded positive effects in reducing bullying and victimization among diverse samples of students. CONCLUSIONS: Antibullying interventions can reduce bullying in schools. Some interventions show effectiveness with students from racially and ethnically diverse backgrounds. The gains relative to per-student costs were in the range that is considered cost-effective. Most implementation costs are spent on staff training and support. Research on successful implementation of whole-school interventions and additional synthesis of evidence pertaining to program structures would further advance the antibullying evidence base.

Sexual Activity, Function, and Satisfaction in Reproductive-Aged Females Living with Chronic Kidney Disease.

Up to 80% of women living with chronic kidney disease (CKD) experience sexual dysfunction, though its link with sexual activity and sexual satisfaction is not well understood. Among older women with CKD treated with hemodialysis, the majority report sexual inactivity, though few describe sexual difficulty and most report high sexual satisfaction. Whether this applies to reproductive-aged females living with CKD is yet unknown. This study aimed to assess the sexual activity, function, and satisfaction of reproductive-aged females living with CKD. Self-identified females aged 18-51 years with CKD were recruited from nephrology clinics in Calgary, Canada. Sexual activity, function, and satisfaction were assessed with a modified version of the Female Sexual Function Index. Fifty-seven participants were recruited (35% CKD without kidney replacement therapy, 44% CKD treated with hemodialysis, 9% CKD treated with peritoneal dialysis, 12% CKD treated with kidney transplant) and nearly half (47%) reported sexual activity. Among sexually active participants, there was a high prevalence of sexual dysfunction (67%) and only 25% of participants reported sexual satisfaction. A strong relationship between sexual function and satisfaction was identified. Reproductive-aged females living with CKD are sexually active, though experience high rates of sexual dysfunction and dissatisfaction. These findings emphasize the importance of recognition and management of sexual dysfunction in this important population.

Targeting brain tumors with innovative nanocarriers: bridging the gap through the blood-brain barrier.

Background: Glioblastoma multiforme (GBM) is recognized as the most lethal and most highly invasive tumor. The high likelihood of treatment failure arises from the presence of the blood-brain barrier (BBB) and stem cells around GBM, which avert the entry of chemotherapeutic drugs into the tumor mass. Objective: Recently, several researchers have designed novel nanocarrier systems like liposomes, dendrimers, metallic nanoparticles, nanodiamonds, and nanorobot approaches, allowing drugs to infiltrate the BBB more efficiently, opening up innovative avenues to prevail over therapy problems and radiation therapy. Methods: Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases, for example, PubMed, Science Direct, Google Scholar, and others, using specific keyword combinations, including "glioblastoma," "brain tumor," "nanocarriers," and several others. Conclusion: This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management. Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

Social and Emotional Learning Interventions for Preadolescents and Adolescents: Assessing the Evidence Base.

OBJECTIVE: The social and emotional learning (SEL) framework is widely recognized as being effective for developing social and emotional competencies among students of all ages. However, the evidence for specific intervention models with older student populations is less established. The objective of this systematic review was to rate the evidence supporting the effectiveness of SEL interventions aimed at improving mental health outcomes among preadolescents and adolescents. METHODS: A search of major databases, gray literature, and evidence base registries was conducted to identify studies published from 2008 to 2022 that assessed the effects of SEL interventions on mental health outcomes among students ages 10-19 years. The authors rated the evidence for SEL interventions as high, moderate, or low based on established rating criteria. RESULTS: In total, 25 articles reporting on 17 original research studies were reviewed. Sixteen intervention models were assessed, with 11 resulting in improved mental health symptoms; however, no intervention was evaluated in a large enough number of studies to surpass a low evidence rating. Some studies reported cost benefits and high effectiveness of an intervention with students from diverse racial-ethnic or low socioeconomic backgrounds. CONCLUSIONS: SEL interventions can improve mental health outcomes among preadolescents and adolescents. Additional research is needed to strengthen the evidence base for specific intervention models.

Reducing Disruptive and Distracting Behaviors in the Classroom: Assessing the Evidence Base.

OBJECTIVE: Disruptive and distracting behaviors in the classroom, from off-task to aggressive behaviors, negatively affect academic engagement and achievement and can lead to more serious problems, including mental health conditions and substance use disorders. The goals of this systematic review were to assess the level of evidence, using established rating criteria, for interventions aimed at preventing or reducing disruptive and distracting classroom behaviors; identify program components common to multiple interventions; synthesize the evidence in regard to students from different racial-ethnic groups; and conduct an economic analysis of these interventions. METHODS: A search of major databases, gray literature, and evidence base registries was conducted to identify studies published between 2008 and 2022. The authors rated interventions as having high, moderate, or low levels of evidence of effectiveness on the basis of the number and rigor of studies with positive outcomes. RESULTS: Of the 27 interventions identified across 65 studies (N=73 articles), six interventions received a high or moderate evidence rating. The Good Behavior Game was the most frequently studied intervention. Many interventions shared similar program components, including behavioral management, classroom management, emotional-cognitive processes, and skills acquisition. Most articles (86%) were focused on elementary school students. The four interventions rated as having high evidence of effectiveness also showed generally positive outcomes in studies conducted in school settings with racial-ethnic diversity. No studies met the criteria for inclusion in an economic analysis. CONCLUSIONS: With greater use and more research, interventions focusing on reducing disruptive and distracting behaviors have the potential to promote student well-being and prevent mental health conditions.

Characteristics and Demographics of Patients Requiring Emergent Air Medical.

Background: As integrated health systems become more common, interfacility patient transfers will increase and air transport programs will be prioritized. Understanding characteristics of patients triaged to air medical transport will assist with resource allocation and needs assessment. The objective of this study was to investigate the demographics and clinical characteristics of patients that presented to the emergency department (ED) and subsequently required emergent air medical interfacility transport. Methods: This was a retrospective, multicenter study conducted at eight hospitals within Northwell Health, the largest academic health system in New York state. The study was conducted between December 1, 2014, and July 31, 2020, and included patients who presented to an ED and subsequently required emergent air medical interfacility transport. Results: Overall, the median age was 37 years (IQR 4-66), and 231 (54%) subjects were males. The majority of subjects (59%) had no reported comorbidities, arrived by ambulance (52%), and were emergency severity index triage 2 (48%). Frequent indications for transfer were nontraumatic neurologic (37%), pulmonary or respiratory (13%), trauma (12%), and cardiovascular (12%). Most patients were not ventilated before transport (71%). The median time to call for transport at the sending institution was 2:42 hours (IQR 1:14-6:54), and the median length of stay was 4:12 (IQR 2:31-8:48). Most patients were subsequently admitted (96%) at the receiving institution to an intensive care unit (72%). Conclusions: This study describes patients' demographic and clinical characteristics who required emergent air medical transport. Helicopter transport is costly, and data from these patients may further help our understanding of who is transported by air and how important air transport is to the health system.

National Trends and Outcomes of Surgical Aortic Valve Replacement With Concomitant Mitral Valve Surgery.

BACKGROUND: Incidence of multivalvular heart disease is increasing, with aortic stenosis and mitral regurgitation being the most common. Data are limited on outcomes of patients undergoing multivalvular surgery. The purpose of this study was to evaluate contemporary trends and in-hospital outcomes for combined surgical aortic valve replacement (SAVR) and mitral valve repair (MVr) or replacement (MVR). METHODS: We identified patient hospitalizations aged ≥18 years who underwent SAVR + MVr or MVR between 2004 and 2018 using the National Inpatient Sample. Data were weighted to estimate national estimates of the entire US hospitalized population. Exclusion criteria included endocarditis, history of heart transplant or left ventricular assist device, and any other concomitant valve surgery. RESULTS: Between January 1, 2004, and December 31, 2018, there were 68,882 weighted admissions for SAVR with concomitant mitral valve surgery. Overall, in-hospital mortality was 8.34% with significantly higher inpatient mortality in SAVR + MVR group compared with SAVR + MVr group (9.91% vs 5.57%, p < 0.001). During the study period, adjusted in-hospital mortality decreased in both SAVR + MVr group (p-trend 0.004) and SAVR + MVR group (p-trend <0.001). Age ≥70 years was associated with higher in-hospital mortality compared to those < 70 years (9.95% vs 6.70%, p < 0.001). CONCLUSION: Combined aortic and mitral valve surgery is associated with a high risk of in-hospital mortality, especially in patients ≥ 70 years of age. Further research is needed to assess the role of transcatheter approaches in the treatment of multivalvular heart disease.

Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not.

Pediatric coronavirus disease-19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis. Mortality in children appears rare. Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission. It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)- Angiotensin converting enzyme 2 (ACE2). Laboratory findings and chest imaging may not be specific in children with COVID-19. Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions. This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment. The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic.

Diabetes and morbid obesity are associated with higher reoperation rates following microvascular decompression surgery: An ACS-NSQIP analysis.

BACKGROUND: Microvascular decompression (MVD) is the preferred treatment for refractory trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. Despite its high rate of success, MVD carries risk of complications. In this study, we examine outcomes following MVD and identify risk factors associated with adverse outcomes. METHODS: A review of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was performed with CPT code 61458 queried between 2007 and 2014. Demographics, preoperative comorbidities, and 30-day outcomes were analyzed. Univariate and multivariate regression analyses were performed to identify predictors of reoperation and adverse events. RESULTS: Five hundred and six craniotomies were studied. Nineteen (5.5%) instances of 30-day readmission were reported, with 14 (2.8%) patients returning to the operating room. No instances of death or hemorrhage requiring operation were reported. Morbid obesity (body mass index >40) (P = 0.030) and diabetes (P = 0.017) were associated with risk of reoperation. Age, operative time, and indication for surgery were not associated with significant differences in adverse events. CONCLUSIONS: MVD is a common and effective procedure with a relatively safe profile and low 30-day risk of reoperation. Advanced age is not associated with worse outcomes. Obesity and diabetes, however, are associated with increased risk of reoperation and may warrant additional precautions.