The heart of children with steroid-resistant nephrotic syndrome: is it all podocin?

Mutations in the gene NPHS2 encoding podocin are responsible for a recessive form of steroid-resistant nephrotic syndrome (SRNS). The common phenotype is of massive proteinuria in early childhood that tends to progress to end-stage renal failure. Extrarenal manifestations have not been described. Twenty-two children with SRNS from six unrelated Arab families were found to be homozygous for the R138X mutation in NPHS2. Eighteen patients underwent cardiac evaluation at diagnosis of SRNS while they had normal BP and preserved renal function. Cardiac anomalies were detected in 16 (89%) children: Left ventricular hypertrophy in eight, pulmonary stenosis in six, discrete subaortic stenosis in two, and Ebstein anomaly and ventricular septal defect in one each. The remaining four affected individuals were assessed only once they had end-stage renal failure. They had severe left ventricular hypertrophy and experienced repeated episodes of heart failure. Two control groups were equally evaluated. The first consisted of 37 siblings without nephrotic syndrome, of whom only one carrier had a cardiac defect (P < 0.001). None of the second group, which included 22 children with persistent nephrotic syndrome as a result of other causes, had a cardiac anomaly (P < 0.001). Cardiac disorders in homozygotes for mutations in NPHS2 cannot be attributed to an association by chance or to a state of persistent nephrotic syndrome. Because human podocin mRNA is expressed in fetal heart, it is speculated that it may have a role in normal cardiac development. Cardiac evaluation is recommended at the time of diagnosis of SRNS due to mutations in podocin.     

Early and Late Presentations of Graft Arterial Pseudoaneurysm Following Pancreatic Transplantation

Background

Graft pseudoaneurysm (PSA) following pancreatic transplantation (PT) is a rarely reported complication that has significant morbidity and mortality. Few case reports and small series of this complication exist.

Methods

Retrospective review of files of 106 patients who underwent PT at the Tel-Aviv Sourasky Medical center between 1995 and 2010. Accessible asymptomatic patients (n = 35) were referred for graft PSA screening using ultrasound-Doppler.

Results

Eight patients developed graft PSA (8 %). All had early posttransplant sepsis. PSA incidence among patients who had perioperative sepsis is 13 %. Three patients developed early postoperative PSA, presenting as massive abdominal bleeding requiring urgent laparotomy and graft resection. Five patients were diagnosed with late-onset graft PSA between 3 months and 11 years posttransplant: clinical presentations were massive gastrointestinal bleeding (n = 2), acute renal failure (n = 1), and asymptomatic finding on screening ultrasound-Doppler (n = 2, 6 % of screened patients).

Conclusions

PSA following PT occurs in 8 % of patients. Perioperative infection is a risk factor. Early PSAs present as massive intra-abdominal bleeding. PSA may develop years posttransplant, may be asymptomatic, but late rupture is possible and presents as gastrointestinal bleeding. We recommend screening of patients at risk with ultrasound Doppler for early detection and treatment of asymptomatic PSAs.     

Perioperative Complications After Neoadjuvant Chemotherapy With and Without Bevacizumab for Colorectal Liver Metastases

Purpose

Bevacizumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer. Neoadjuvant bevacizumab is commonly used in patients undergoing liver resection. Our purpose was to evaluate whether bevacizumab is associated with increased rate of perioperative complications in patients undergoing hepatic resection for colorectal liver metastases (CRLM).

Methods

Retrospective analysis of patients undergoing hepatic resection for CRLM who received chemotherapy and bevacizumab (group 1, n?=?134), or chemotherapy alone (group 2, n?=?57). We compared demographics, surgical characteristics, and perioperative course.

Results

Perioperative complications developed in 35 % of patients in group 1, and 47 % in group 2 (p?=?0.11). Of those complications, 15 (11.2 %) in group 1, and 5 (8.8 %) in group 2 were considered major (p?=?0.617). Four patients, all of whom received preoperative bevacizumab, developed enteric leaks following combined liver and bowel resection. The rate of anastomotic leak in group 1 was 10 %, compared with 0 in group 2, p?=?0.56.

Conclusion

Neoadjuvant chemotherapy along with bevacizumab was not associated with an increased risk of postoperative complications after hepatic resection. Possible association of increased morbidity with simultaneous bowel and liver resections following bevacizumab administration was found and we recommend avoiding such treatment combination.     

Comparison of VivaSight double‐lumen tube with a conventional double‐lumen tube in adult patients undergoing video‐assisted thoracoscopic surgery

The efficiency of a double‐lumen tube depends on its position in the airways, which can be verified by fibreoptic bronchoscopy. The VivaSight DL is a single‐use double‐lumen tube with a camera embedded in the tube's right side. The view from the camera appears continuously on a monitor. In this prospective study of 71 adult patients, we compared intubation times using either the VivaSight DL or a conventional double‐lumen tube. Median (IQR [range]) duration of intubation with visual confirmation of tube position was significantly reduced using the VivaSight DL compared with the conventional double‐lumen tube (51 (42–60 [35–118]) s vs 264 (233–325 [160–490]) s, respectively, p < 0.0001). None of the patients allocated to the VivaSight DL required fibreoptic bronchoscopy during intubation or surgery. The VivaSight DL enables significantly more rapid intubation compared with the conventional double‐lumen tube.     

The rs12594956 polymorphism in the NRF-2 gene is associated with top-level Spanish athlete's performance status

ObjectivesTo determine the association between the nuclear respiratory factor 2 (NRF-2) polymorphisms and elite athletic performance.DesignWe compared the genotype and allele frequencies of the NRF-2 A/C (rs12594956), NRF-2 A/G (rs7181866), and NRF-2 C/T (rs8031031) polymorphisms between world-class endurance athletes (n = 89), elite power-oriented athletes (n = 38), and non-athletic controls (n = 110) of the same Caucasian (Spanish) origin.MethodsGenomic DNA was extracted from peripheral EDTA-treated, anti-coagulated blood using a standard protocol. Genotyping was performed using polymerase chain reaction (PCR).ResultsThe frequency of the AA genotype of the NRF-2 A/C (rs12594956) polymorphism was significantly higher in endurance athletes compared with power athletes (P < 0.01) and controls (P < 0.01) (48% vs. 13% and 21%, respectively). The likelihood of having the AA (rs12594956) genotype was higher in elite endurance athletes compared with controls [odds ratio (OR): 3.536, 95% confidence interval (CI): 1.903–6.571] and elite power athletes (OR: 6.170, 95%CI: 2.206–17.253).ConclusionsOur results suggest that the NRF-2 A/C polymorphism might belong to a growing group of polymorphisms associated with endurance performance at the elite level. However, it is important to replicate these findings in other groups of elite athletes using larger sample sizes.     

Tired and misconnected: A breakdown of brain modularity following sleep deprivation

Sleep deprivation (SD) critically affects a range of cognitive and affective functions, typically assessed during task performance. Whether such impairments stem from changes to the brain's intrinsic functional connectivity remain largely unknown. To examine this hypothesis, we applied graph theoretical analysis on resting‐state fMRI data derived from 18 healthy participants, acquired during both sleep‐rested and sleep‐deprived states. We hypothesized that parameters indicative of graph connectivity, such as modularity, will be impaired by sleep deprivation and that these changes will correlate with behavioral outcomes elicited by sleep loss. As expected, our findings point to a profound reduction in network modularity without sleep, evident in the limbic, default‐mode, salience and executive modules. These changes were further associated with behavioral impairments elicited by SD: a decrease in salience module density was associated with worse task performance, an increase in limbic module density was predictive of stronger amygdala activation in a subsequent emotional‐distraction task and a shift in frontal hub lateralization (from left to right) was associated with increased negative mood. Altogether, these results portray a loss of functional segregation within the brain and a shift towards a more random‐like network without sleep, already detected in the spontaneous activity of the sleep‐deprived brain. Hum Brain Mapp 38:3300–3314, 2017. © 2017 Wiley Periodicals, Inc.     

Freezing of gait affects quality of life of peoples with Parkinson's disease beyond its relationships with mobility and gait.

The aim of this study was to examine the association between freezing of gait (FOG) and quality of life (QoL) in patients with Parkinson's disease (PD). PD patients (n = 118) completed the PDQ-39 (QoL) and FOG-Q questionnaires. Disease severity was assessed by the Hoehn and Yahr (H&Y) staging and the Unified Parkinson's Disease Rating Scale (UPDRS). The relations between those parameters were assessed using regression models. 66 men and 52 women (mean age 65.8 +/- 10.2 years, UPDRS total score 48.4 +/- 17.1, disease duration 8.5 +/- 5.8 years, H&Y stage 2.7 +/- 0.8) participated. FOG severity had a significant effect on QoL (P < 0.0015), accounting for disease severity assessed by UPDRS. Specifically, FOG severity was correlated with all the dimensions of the PDQ-39 except for stigma and social support, as follows: with mobility, bodily discomfort, activity of daily living (ADL) (P < 0.005 in all), with emotional, communication, and cognition (P < 0.05 in all). FOG severity (FOG-Q) was also found to affect a modified PDQ total score, without the mobility aspect (P = 0.0081). FOG should be viewed as a highly important symptom with regard to QoL of PD patients beyond its effect on gait and mobility. On the basis of the present results, special attention should be given to FOG in the treatment of patients with PD.