Intensified electrical stimulation targeting lateral and medial prefrontal cortices for the treatment of social anxiety disorder: A randomized,double-blind,parallel-group,dose-comparison study

BackgroundSocial Anxiety Disorder (SAD) is the most common anxiety disorder while remains largely untreated. Disturbed amygdala-frontal network functions are central to the pathophysiology of SAD, marked by hypoactivity of the lateral prefrontal cortex (PFC), and hypersensitivity of the medial PFC and the amygdala. The objective of this study was to determine whether modulation of the dorsolateral and medial PFC activity with a novel intensified stimulation protocol reduces SAD core symptoms, improves treatment-related variables, and reduces attention bias to threatening stimuli.MethodsIn this randomized, sham-controlled, double-blind trial, we assessed the efficacy of an intensified stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) in two intensities (1 vs 2 mA) compared to sham stimulations. 45 patients with SAD were randomized in three tDCS arms (1-mA, 2-mA, sham). SAD symptoms, treatment-related variables (worries, depressive state, emotion regulation, quality of life), and attention bias to threatening stimuli (dot-probe paradigm) were assessed before and right after the intervention. SAD symptoms were also assessed at 2-month follow-up.ResultsBoth 1-mA and 2-mA protocols significantly reduced fear/avoidance symptoms, worries and improved, emotion regulation and quality of life after the intervention compared to the sham group. Improving effect of the 2-mA protocol on avoidance symptoms, worries and depressive state was significantly larger than the 1-mA group. Only the 2-mA protocol reduced attention bias to threat-related stimuli, the avoidance symptom at follow-up, and depressive states, as compared to the sham group.ConclusionsModulation of lateral-medial PFC activity with intensified stimulation can improve cognitive control, motivation and emotion networks in SAD and might thereby result in therapeutic effects. These effects can be larger with 2-mA vs 1-mA intensities, though a linear relationship between intensity and efficacy should not be concluded. Our results need replication in larger trials.     

颈型颈椎病患者不同年龄段颈椎功能障碍类型的差异

目的 研究颈型颈椎病患者不同年龄段颈椎功能障碍类型的差异。方法 纳入294例颈型颈椎病患者,采用颈椎功能障碍指数(NDI)评估颈椎功能(包括颈痛及相关的症状、日常生活活动能力),比较不同年龄段患者在颈椎功能障碍类型上的差异。结果 30岁以上各年龄段总的颈椎功能障碍评分均较18～30岁严重；其中31～40岁侧重的功能障碍类型为：头痛、工作；41～50岁：疼痛、头痛、工作、驾驶；51～60岁：疼痛、头痛、睡眠、工作、个人护理、娱乐；61～70岁：睡眠、工作。结论 不同年龄段的颈型颈椎病患者在功能障碍类型上存在一定的差异,临床上治疗颈椎病除了缓解局部症状,还要根据不同年龄段功能障碍的类型进行对应的康复治疗。     

Cost-effectiveness of maternal immunization against neonatal invasive Group B Streptococcus in the Netherlands

BackgroundNeonatal invasive Group B Streptococcus (GBS) infection causes considerable disease burden in the Netherlands. Intrapartum antibiotic prophylaxis (IAP) prevents early-onset disease (EOD), but has no effect on late-onset disease (LOD). A potential maternal GBS vaccine could prevent both EOD and LOD by conferring immunity in neonates.ObjectiveExplore under which circumstances maternal vaccination against GBS would be cost-effective as an addition to, or replacement for the current risk factor-based IAP prevention strategy in the Netherlands.MethodsWe assessed the maximum cost-effective price per dose of a trivalent (serotypes Ia, Ib, and III) and hexavalent (additional serotypes II, IV, and V) GBS vaccine in addition to, or as a replacement for IAP. To project the prevented costs and disease burden, a decision tree model was developed to reflect neonatal GBS disease and long-term health outcomes among a cohort based on 169,836 live births in the Netherlands in 2017.ResultsUnder base-case conditions, maternal immunization with a trivalent vaccine would gain 186 QALYs and prevent more than €3.1 million in health care costs when implemented in addition to IAP. Immunization implemented as a replacement for IAP would gain 88 QALYs compared to the current prevention strategy, prevent €1.5 million in health care costs, and avoid potentially ~ 30,000 IAP administrations. The base-case results correspond to a maximum price of €58 per dose (vaccine + administration costs; using a threshold of €20,000/QALY). Expanding the serotype coverage to a hexavalent vaccine would only have a limited additional impact on the cost-effectiveness in the Netherlands.ConclusionsA maternal GBS vaccine could be cost-effective when implemented in addition to the current risk factor-based IAP prevention strategy in the Netherlands. Discontinuation of IAP would save costs and prevent antibiotic use, however, is projected to lead to a lower health gain compared to vaccination in addition to IAP.     

Synchronous Periprosthetic Joint Infections: High Mortality,Reinfection, and Reoperation

BackgroundSynchronous periprosthetic joint infections (PJIs) are a catastrophic complication with potentially high mortality. We aimed to report mortality, risk of reinfection, revision, reoperation, and implant survivorship after synchronous PJIs.MethodsWe identified 34 patients treated for PJI in more than one joint within a single 90-day period from 1990 to 2018. PJIs involved bilateral knee arthroplasty (27), bilateral hip arthroplasty (4), 1 knee arthroplasty and 1 elbow arthroplasty (1), 1 knee arthroplasty and 1 shoulder arthroplasty (1), and bilateral hip and knee arthroplasty (1). Irrigation and debridement with component retention was performed in 23 patients, implant resection in 10 patients, and a combination of irrigation and debridement with component retention and implant resection in 1 patient. A competing risk model was used to analyze implant survivorship, and Kaplan-Meier survival was used for patient mortality. Mean follow-up was 6 years.ResultsMortality was high at 18% at 30 days and 27% at 1 year. The 1-year cumulative incidence of any reinfection was 13% and 27% at 5 years. The 1-year cumulative incidence of any revision or implant removal was 6% and 20% at 5 years. The 1-year cumulative incidence of unplanned reoperation was 25% and 35% at 5 years. Rheumatoid arthritis was associated with increased risk of mortality (HR 7, P < .01), as was liver disease (HR 4, P = .02).ConclusionIn the largest series to date, patients with synchronous PJIs had a high 30-day mortality rate of 18%, and one-fourth underwent unplanned reoperation within the first year.     

Fatal unexpected death due to X-linked lymphoproliferative disease

X-linked lymphoproliferative disease (XLP) is a rare immunodeficiency disease characterized by severe immune disorder and extreme vulnerability to Epstein-Barr virus (EBV) infections. Here we report a 14-month-old Chinese boy presenting with fulminant infectious mononucleosis (FIM) following EBV infection, and died of hepatic failure within one week of disease progression. Postmortem examination revealed icterus, ascites, extensive enlarged mesenteric lymph nodes and hepatosplenomegaly. Histopathological examination showed diffuse proliferation of cytotoxic T lymphoid cells and hemophagocytosis in multiple organs. The family history revealed his brother had died under similar circumstances at 5 five years of age. The cause of death of the boy was ascribed to XLP. To the best of our knowledge, there is few autopsy-confirmed XLP case in the forensic practice. The complicated manifestations and systemic pathological changes should be well recognized by clinicians and forensic pathologists.     

Cerebrovascular events during pregnancy and puerperium

Though cerebrovascular complications of pregnancy remain relatively rare, they represent a potentially devastating event that necessitates prompt identification and treatment. Eighteen percent of strokes occurring in young women are linked to pregnancy. They occur mostly in the third trimester or during the post-partum period. Their biggest risk factors are hypertension, preeclampsia/eclampsia and migraine. Cerebrovascular events occurring during this period may involve specific pathophysiological processes that include embolic phenomena or endothelial dysfunction, but can also have common etiologies that are simply favored by the context of pregnancy. Thus, posterior encephalopathy and vasoconstriction cerebral syndrome are relatively frequently involved in cerebrovascular complications of pregnancy. Other very specific causes like amniotic fluid embolism or postpartum cardiomyopathy can also be responsible for such events. The management of stroke during pregnancy must be multidisciplinary and include a neurovascular expertise. Some conditions can lead to a long-life follow-up and modify the management of a future pregnancy.     

Immunomodulatory and immunoregulatory nanomedicines for autoimmunity

Autoimmune diseases, caused by cellularly and molecularly complex immune responses against self-antigens, are largely treated with broad-acting, non-disease-specific anti-inflammatory drugs. These compounds can attenuate autoimmune inflammation, but tend to impair normal immunity against infection and cancer, cannot restore normal immune homeostasis and are not curative. Nanoparticle (NP)- and microparticle (MP)-based delivery of immunotherapeutic agents affords a unique opportunity to not only increase the specificity and potency of broad-acting immunomodulators, but also to elicit the formation of organ-specific immunoregulatory cell networks capable of inducing bystander immunoregulation. Here, we review the various NP/MP-based strategies that have so far been tested in models of experimental and/or spontaneous autoimmunity, with a focus on mechanisms of action.