Infanticide vs. inherited cardiac arrhythmias.

AIMS: In 2003, an Australian woman was convicted by a jury of smothering and killing her four children over a 10-year period. Each child died suddenly and unexpectedly during a sleep period, at ages ranging from 19 days to 18 months. In 2019 we were asked to investigate if a genetic cause could explain the children's deaths as part of an inquiry into the mother's convictions. METHODS AND RESULTS: Whole genomes or exomes of the mother and her four children were sequenced. Functional analysis of a novel CALM2 variant was performed by measuring Ca2+-binding affinity, interaction with calcium channels and channel function. We found two children had a novel calmodulin variant (CALM2 G114R) that was inherited maternally. Three genes (CALM1-3) encode identical calmodulin proteins. A variant in the corresponding residue of CALM3 (G114W) was recently reported in a child who died suddenly at age 4 and a sibling who suffered a cardiac arrest at age 5. We show that CALM2 G114R impairs calmodulin's ability to bind calcium and regulate two pivotal calcium channels (CaV1.2 and RyR2) involved in cardiac excitation contraction coupling. The deleterious effects of G114R are similar to those produced by G114W and N98S, which are considered arrhythmogenic and cause sudden cardiac death in children. CONCLUSION: A novel functional calmodulin variant (G114R) predicted to cause idiopathic ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, or mild long QT syndrome was present in two children. A fatal arrhythmic event may have been triggered by their intercurrent infections. Thus, calmodulinopathy emerges as a reasonable explanation for a natural cause of their deaths.

Application of the Preventable Shunt Revision Rate to an Adult Population.

BACKGROUND: The preventable shunt revision rate (PSRR) was recently introduced in pediatric hydrocephalus as a quality metric for shunt surgery. We evaluated the PSRR in an adult hydrocephalus population. METHODS: All ventricular shunt operations (January 1, 2013 to March 31, 2018) performed at a university-based teaching hospital were included. For any index surgery (de novo or revision) resulting in reoperation within 90 days, the index surgery details were collected, and a consensus decision was reached regarding whether the failure had been potentially avoidable. Preventable failure was defined as failure due to infection, malposition, disconnection, migration, or kinking. The 90-day shunt failure rate and PSRR were calculated. Bivariate analyses were performed to evaluate the individual effects of each independent variable on preventable shunt failure. RESULTS: A total of 318 shunt operations had been performed in 245 patients. Most patients were women (62%), with a median age of 48.2 years (interquartile range, 31.2-63.2 years). Most had had ventriculoperitoneal shunts placed (86.5%), and just more than one half were new shunts (51.6%). A total of 53 cases (16.7%) in 42 patients experienced shunt failure within 90 days of the index operation. Of these, 27 failures (8.5% of the total cases; 51% of the failures) were considered potentially preventable. The most common reasons were infection (37%; n = 10) and malposition of the proximal and distal catheters (both 25.9%; n = 7). Age was the only statistically significant difference between the 2 groups, with the patients experiencing preventable shunt failure older than those without preventable shunt failure (51.4 vs. 37.1 years; P = 0.017). CONCLUSIONS: The 90-day PSRR can be applied to an adult population and serve as a quality metric.

Postgraduate publishing output in pediatric neurosurgery: correlation with fellowship site and individual scholars.

OBJECTIVE: The objective of this study was to analyze the publication output of postgraduate pediatric neurosurgery fellows for a 10-year period as well as identify 25 individual highly productive pediatric neurosurgeons. The correlation between academic productivity and the site of fellowship training was studied. METHODS: Programs certified by the Accreditation Council for Pediatric Neurosurgery Fellowships that had 5 or more graduating fellows from 2006 to 2015 were included for analysis. Fellows were queried using Scopus for publications during those 10 years with citation data through 2017. Pearson correlation coefficients were calculated, comparing program rankings of faculty against fellows using the revised Hirsch index (r-index; primary) and Hirsch index (h-index; secondary). A list of 25 highly accomplished individual academicians and their fellowship training locations was compiled. RESULTS: Sixteen programs qualified with 152 fellows from 2006 to 2015; 136 of these surgeons published a total of 2009 articles with 23,735 citations. Most publications were pediatric-specific (66.7%) clinical articles (93.1%), with middle authorship (55%). Co-investigators were more likely from residency than fellowship. There was a clustering of the top 7 programs each having total publications of around 120 or greater, publications per fellow greater than 12, more than 1200 citations, and adjusted ir10 (revised 10-year institutional h-index) and ih10 (10-year institutional h-index) values of approximately 2 or higher. Correlating faculty and fellowship program rankings yielded correlation coefficients ranging from 0.53 to 0.80. Fifteen individuals (60%) in the top 25 (by r5 index) list completed their fellowship at 1 of these 7 institutions. CONCLUSIONS: Approximately 90% of fellowship-trained pediatric neurosurgeons have 1 or more publications, but the spectrum of output is broad. There is a strong correlation between where surgeons complete their fellowships and postgraduate publications.

Gluteal muscle activity during weightbearing and non-weightbearing exercise.

BACKGROUND: Researchers suggest that decreased strength of the gluteus medius (GMed) and the gluteus maximus (GMax) muscles contributes to the etiology of various orthopedic pathologies of the knee. Currently, equivocal evidence exists regarding Electromyography (EMG) activity of gluteal musculature during weightbearing (WB) and non-weightbearing (NWB) exercise. The purpose of this study was to compare GMed and GMax muscle activation during WB functional exercise and NWB 10 repetition maximum (RM) exercises. METHODS: Surface EMG electrodes recorded the muscle activity of the GMax and GMed as subjects performed three sets of 10 repetitions of the following exercises: (1) forward step-up, (2) lateral step-up, (3) 10 repetition maximum (10 RM) side-lying hip abduction and (4) 10 RM prone hip extension. The 10 RM resistances were determined one week prior to data collection. RESULTS: The GMed was recruited significantly more during side-lying 10 RM than the remaining exercises (side-lying, 99.9±17% vs. lateral step-up, 61±20%; Forward step-up, 62.7±18.2%; prone, 38±22.2%)(p<0.001). The GMax was recruited to the greatest extent during prone 10 RM hip extension (prone, 100.7±14.5% vs. forward step-up, 28.7±18.7%; lateral step-up, 31±19.9%; side-lying, 38±23.3%)(p<0.001). DISCUSSION: These results suggest that performing a 10 RM NWB exercise results in greater muscle activation than two functional WB exercise without load in young, healthy individuals. In addition, forward and lateral step-ups failed to effectively recruit the GMax at a high enough level to achieve a strengthening stimulus. The GMed was recruited to a higher extent than the GMax during the stepping tasks which might be further augmented if the activity is performed with an additional external load. LEVEL OF EVIDENCE: III.

Patellofemoral joint kinetics while squatting with and without an external load.

STUDY DESIGN: Single-group repeated measures design. OBJECTIVE: To quantify patellofemoral joint reaction forces and stress while squatting with and without an external load. BACKGROUND: Although squatting exercises in the rehabilitation setting are often executed to a relatively shallow depth in order to avoid the higher joint forces associated with increased knee flexion, objective criteria for ranges of motion have not been established. METHODS AND MEASURES: Fifteen healthy adults performed single-repetition squats to 90 degrees of knee flexion without an external load and with an external load (35% of the subject's body weight [BW]). Anthropometric data, three-dimensional kinematics, and ground reaction forces were used to calculate knee extensor moments (inverse dynamics approach), while a biomechanical model of the patellofemoral joint was used to quantify the patellofemoral joint reaction forces and patellofemoral joint stress. Data were analyzed during the eccentric (0-90 degrees) and concentric (90-0 degrees phases of the squat maneuver. RESULTS: In both conditions, knee extensor moments, patellofemoral joint reaction forces, and patellofemoral joint stress increased significantly with greater knee flexion angles (P < 0.05). Peak patellofemoral joint force and stress was observed at 90 degrees of knee flexion. Patellofemoral joint stress at 45 degrees, 60 degrees, 75 degrees, and 90 degrees of knee flexion during the eccentric phase, and at 75 degrees and 90 degrees during the concentric phase, was significantly greater in the loaded trials versus the unloaded trials. CONCLUSION: The data indicate that during squatting, patellofemoral joint stress increases as the knee flexion angle increases, and that the addition of external resistance further increases patellofemoral joint stress. These findings suggest that in order to limit patellofemoral joint stress during squatting activities, clinicians should consider limiting terminal joint flexion angles and resistance loads.