Outcome of isolated posterior cruciate ligament reconstruction at mean 6.3-year follow up: a consecutive case series

Objectives: There is a paucity of reporting on surgical outcomes of isolated posterior cruciate ligament reconstruction (PCLR). We hypothesize that isolated PCL injuries failing nonoperative treatment achieve good outcomes and are able to return to sport following PCLR.

Methods: A retrospective analysis was performed to identify patients with isolated PCL injuries that underwent reconstruction between 2001 and 2014. Patients with multi-ligamentous injury or another concomitant knee pathology were excluded. Medical records were reviewed for demographic, clinical and operative data. Patients were contacted for administration of a telephone-based questionnaire which included the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form, Lysholm-Tegner scales, Marx activity scale (MAS), return to sport status, and patient satisfaction instruments.

Results: A total of 15 isolated PCL reconstructions in 14 patients with a mean age of 27.5 years (range 17–43) met the study inclusion criteria; mean follow up was 6.3 years (range 1.4–15.2). Pre-operatively, the primary complaint was knee instability in all patients; on physical examination, lack of a firm end point during posterior drawer testing was found in 93% (14/15) of the knees. In total, 12 of 15 knees underwent transtibial, single-bundle PCLR and three of 15 underwent tibial inlay, double bundle PCLR. Graft types included: quadriceps autograft (7/15), Achilles allograft (6/15), and hamstring autograft (2/15). There were no graft failures in our patient cohort. At most recent follow up the mean scores respectively on the IKDC form, Lysholm-Tegner scales and MAS were (standard deviation): 77.3 (16.5), 83.1 (17.9), 6.13 (2.6), and 7.1 (6.0). All fourteen patients were athletes prior to their injury and 79% (11/14) returned to sport and overall patient satisfaction was 9.2/10.

Conclusions: Isolated PCLR provides good outcomes at mean medium-term follow up with restoration of function, high rate of return to sport and overall patient satisfaction.     

Increased activation of the fear neurocircuitry in children exposed to violence

Most studies investigating the effect of childhood trauma on the brain are retrospective and mainly focus on maltreatment, whereas different types of trauma exposure such as growing up in a violent neighborhood, as well as developmental stage, could have differential effects on brain structure and function. The current magnetic resonance imaging study assessed the effect of trauma exposure broadly and violence exposure more specifically, as well as developmental stage on the fear neurocircuitry in 8‐ to 14‐year‐old children and adolescents (N = 69). We observed reduced hippocampal and increased amygdala volume with increasing levels of trauma exposure. Second, higher levels of violence exposure were associated with increased activation in the amygdala, hippocampus, and ventromedial prefrontal cortex during emotional response inhibition. This association was specifically observed in children younger than 10 years. Finally, increased functional connectivity between the amygdala and brainstem was associated with higher levels of violence exposure. Based on the current findings, it could be hypothesized that trauma exposure during childhood results in structural changes that are associated with later risk for psychiatric disorders. At the same time, it could be postulated that growing up in an unsafe environment leads the brain to functionally adapt to this situation in a way that promotes survival, where the long‐term costs or consequences of these adaptations are largely unknown and an area for future investigations.     

Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development. Direct acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.     

Worsening head bleeds in elderly blunt head trauma patients taking antithrombotics: Delayed CT head fails to change management

Background

Most elderly trauma patients suffer blunt head injury and many utilize antithrombotic (AT) medications. The utility of delayed CT-head (D-CTH) in neurologically intact elderly patients using AT who have an intracranial hemorrhage (ICH) on presentation is unknown. We hypothesized that D-CTH would not alter clinical management and aimed to evaluate the role of D-CTH in this population.

Frequency of Automatic Stimulations in Responsive Vagal Nerve Stimulation in Patients With Refractory Epilepsy

BackgroundIn vagal nerve stimulation (VNS) therapy, the release of VNS model 106 (AspireSR) allowed for responsive VNS (rVNS). rVNS utilizes a cardiac-based seizure detection algorithm to detect seizure-induced tachycardia to trigger additional stimulation. There are some studies suggesting clinical benefits of rVNS over traditional VNS, but the performance and significance of autostimulation mode in clinical practice are poorly understood.ObjectivesTo assess the effect of initiation of rVNS therapy and altered stimulation settings on the number of daily stimulations and energy consumption in VNS therapy and to compare autostimulation performance in different epilepsy types.Materials and MethodsRetrospective follow-up of 30 patients with drug-resistant epilepsy treated with rVNS including 17 new implantations and 13 battery replaces at a single center in Finland. Our data consist of 208 different stimulation periods, that is, episodes with defined stimulation settings and both autostimulation and total stimulation performance-related data along with clinical follow-up.ResultsThe variation in autostimulation frequency was highly dependent on the duration of the OFF-time and autostimulation threshold (p < 0.05). There was a large additional effect of autostimulation mode on therapy time and energy consumption with longer OFF-times, but a minor effect with shorter OFF-times. Significantly more autostimulations were triggered in the temporal lobe and multifocal epilepsies than in extratemporal lobe epilepsies.ConclusionsThe initiation of autostimulation mode in VNS therapy increased the total number of stimulations. Shortening the OFF-time leads to a decreased number and share of automatic activations. Epilepsy type may affect autostimulation activity.     

中国5~18岁人群遗尿症患病率的横断面调查

目的 了解中国儿童和青少年遗尿症的患病情况。方法 横断面调查，以中国医师协会肾脏专委会中国儿童遗尿疾病管理协作组（简称：协作组）成员与所在省、自治区和直辖市有工作联系的区县为抽样单位。遗尿症诊断标准为年龄≥5岁，3个月内出现尿床事件≥1次；尿床指夜间睡眠中排尿于床上或尿湿衣裤。调查时间为2017年4月20日至2017年5月12日；调查人群为中国5~18岁儿童及青少年，分为幼儿园（5~6岁）、小学（~12岁），初中（~15岁）和高中（~18岁）。每个区县样本量需＞3 073人。自行设计遗尿症调查问卷，本文主要分析基本人口学信息和尿床事件。由儿童或青少年的家长或照护者在手机或其他安装有微信应用终端设备上填写问卷。结果 24个协作组成员所在省、自治区和直辖市中的34个区县中的225所幼儿园和学校参与了调查，其中幼儿园82所，小学61所，初中49所，高中33所。调查目标样本人群129 952人，进入本文分析的调查问卷100 071份（77.0%）。男52 074份，平均年龄（11.0±3.4）岁，汉族占92.5%，幼儿园、小学、初中、高中人数比例约为1∶5∶2∶1。中国儿童和青少年遗尿症患病率为4.8%（4 821/100 071）；幼儿园、小学、初中、高中遗尿患病率分别为12.1%、5.1%、1.1%和1.4%；各年龄男孩遗尿症患病率均高于同年龄的女孩；中国境内6大行政区（华北、东北、华东、中南、西南、西北）以样本人群年龄构成比进行标准化后，其患病率分别为4.2%，3.7%、4.6%、5.8%、5.1%和4.9%；4 821名遗尿症患儿中，轻、中、重度遗尿症患儿分别占81.4%、13.5%和5.1%；重度遗尿症幼儿园、小学、初中和高中组比例为6.9%、3.7%、5.3%和10.0%。结论 中国幼儿园、小学、初中、高中人群遗尿患病率分别为12.1%、5.1%、1.1%和1.4%，儿童遗尿症患病率总体为4.8%。幼儿园及高中组重度遗尿症的比例较高。     

Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma development and growth in vivo

Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for Braf^V600E‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (Tyr^CreERT2/+; Braf^{LSL‐V600E/+}; Pten^flox/flox) to Sirt5^?/? knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5^?/? mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for Braf^V600E‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.