Mutation of POC1B in a Severe Syndromic Retinal Ciliopathy

We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next‐generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole‐exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for the formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photoreceptor connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes homozygosity for p.Arg106Pro_POC1B in a family with nonsyndromic cone‐rod dystrophy. The phenotype associated with homozygous p.Arg106Pro_POC1B may thus be highly variable, analogous to homozygous p.Leu710Ser in WDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal integrity, and we propose POC1B mutations as a probable cause for JBTS with severe PKD.     

One-stop routing for surgical interventions: a cost-analysis of endoscopic groin repair

Surgical Endoscopy - Single-visit (SV) totally extraperitoneal (TEP) inguinal hernia repair is an efficient service without impairment of safety or complication rate. Data on the economic impact of...     

Challenges and satisfaction in Cardiothoracic Surgery Residency Programmes: insights from a Europe-wide survey

Open in a separate window OBJECTIVESThe increasing complexity of surgical patients and working time constraints represent challenges for training. In this study, the European Association for Cardio-Thoracic Surgery Residents’ Committee aimed to evaluate satisfaction with current training programmes across Europe. METHODSWe conducted an online survey between October 2018 and April 2019, completed by a total of 219 participants from 24 countries.RESULTSThe average respondent was in the fourth or fifth year of training, mostly on a cardiac surgery pathway. Most trainees follow a 5–6-year programme, with a compulsory final certification exam, but no regular skills evaluation. Only a minority are expected to take the examination by the European Board of Cardiothoracic Surgery. Participants work on average 61.0 ± 13.1 h per week, including 27.1 ± 20.2 on-call. In total, only 19.7% confirmed the implementation of the European Working Time Directive, with 42.0% being unaware that European regulations existed. Having designated time for research was reported by 13.0%, despite 47.0% having a postgraduate degree. On average, respondents rated their satisfaction 7.9 out of 10, although 56.2% of participants were not satisfied with their training opportunities. We found an association between trainee satisfaction and regular skills evaluation, first operator experience and protected research time.CONCLUSIONSOn average, residents are satisfied with their training, despite significant disparities in the quality and structure of cardiothoracic surgery training across Europe. Areas for potential improvement include increasing structured feedback, research time integration and better working hours compliance. The development of European guidelines on training standards may support this.     

A mutation update on the LDS‐associated genes TGFB2/3 and SMAD2/3

The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor‐β (TGF‐β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF‐β signaling. More recently, TGF‐β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF‐β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF‐β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.     

Magnetic resonance imaging of patellofemoral osteoarthritis: intertester reliability and associations with knee pain and function

Clinical Rheumatology - We examined the intertester reliability of patellofemoral compartment (PFC) osteoarthritis (OA) severity using magnetic resonance images (MRI) and a modified Kellgren and...     

Trends in Nontherapeutic Laparotomy Rates in Patients Undergoing Surgical Therapy for Hepatic Colorectal Metastases

Surgery is the treatment of choice in selected patients with hepatic colorectal metastases. Despite improvements in preoperative imaging, patients can undergo unnecessary nontherapeutic laparotomy. The aim of this study was to examine trends in nontherapeutic laparotomy rates in patients undergoing planned surgical therapy for hepatic colorectal metastases. Data from 530 operations (461 patients) undergoing potentially curative surgical therapy for colorectal liver metastases between 1994 and 2005 were analyzed. The incidence of nontherapeutic laparotomy was determined and factors associated with nontherapeutic laparotomy were identified. Overall, 49 nontherapeutic laparotomies were performed (9.2%). Higher nontherapeutic laparotomy rates were seen in patients with multiple metastases and tumor size >5 cm (both P < 0.05). Preoperative positron emission tomography (PET) imaging was associated with lower risk of nontherapeutic laparotomy [5.6% versus 12.4%, P = 0.009, odds ratio (OR) = 0.42]. At laparotomy, extrahepatic findings were the reason for nontherapeutic laparotomy in 44.9% of cases. The nontherapeutic laparotomy rate significantly decreased over time (14.9% for 1994–1997 versus 9.6% for 1998–2001 versus 4.7% for 2002–2005; P = 0.003). While patients in each time period were similar with regard to tumor specific factors, utilization of PET imaging (P < 0.001) as well as resection plus ablation (P = 0.004) increased over time. We conclude that prevalence of nontherapeutic laparotomy for patients undergoing surgical exploration for hepatic colorectal metastases has decreased significantly in recent years to less than 5%. The reasons for this trend are probably multifactorial and may include improved preoperative assessment, such as PET imaging, as well as salvage surgical options.     

Specificity of the anti-glycolytic activity of 3-bromopyruvate confirmed by FDG uptake in a rat model of breast cancer

Summary   Purpose: To evaluate the anti-glycolytic effects of 3-BrPA on rats bearing RMT mammary tumors, by determining FDG uptake after intravenous administration of the therapeutic dose. Materials and Methods: Sixteen rats bearing RMT tumors were treated either with 15 mM 3-BrPA in 2.5 ml of PBS or with 2.5 ml of PBS. After treatment, all rats received FDG and were sacrificed 1 h later. Results: 3-BrPA treatment significantly decreased FDG uptake in tumors by 77% (p = 0.002). FDG uptake did not significantly decrease in normal tissues after treatment. Conclusion: Our study showed that 3-BrPA exhibits a strong anti-glycolytic effect on RMT cells implanted in rats. Buijs and Vossen contributed equally to this work.