Citations

Abstract Motivation: Single-cell RNA-sequencing technology allows detection of gene expression at the single-cell level. One typical feature of the data is a bimodality in the cellular distribution even for highly expressed genes, primarily caused by a proportion of non-expressing cells. The standard and the over-dispersed gamma-Poisson models that are commonly used in bulk-cell RNA-sequencing are not able to capture this property. Results: We introduce a beta-Poisson mixture model that can capture the bimodality of the single-cell gene expression distribution. We further integrate the model into the generalized linear model framework in order to perform differential expression analyses. The whole analytical procedure is called BPSC. The results from several real single-cell RNA-seq datasets indicate that ∼90% of the transcripts are well characterized by the beta-Poisson model; the model-fit from BPSC is better than the fit of the standard gamma-Poisson model in > 80% of the transcripts. Moreover, in differential expression analyses of simulated and real datasets, BPSC performs well against edgeR, a conventional method widely used in bulk-cell RNA-sequencing data, and against scde and MAST, two recent methods specifically designed for single-cell RNA-seq data. Availability and Implementation: An R package BPSC for model fitting and differential expression analyses of single-cell RNA-seq data is available under GPL-3 license at https://github.com/nghiavtr/BPSC . Contact: yudi.pawitan@ki.se or mattias.rantalainen@ki.se Supplementary information: Supplementary data are available at Bioinformatics online.

AbstractBackgroundParathyroidectomy is a definitive treatment for primary hyperparathyroidism. Patients contemplating this intervention will benefit from knowledge regarding the expected outcomes and potential risks of the currently available surgical options.PurposeTo appraise and summarize the available evidence regarding benefits and harms of minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE).Data sourcesA comprehensive search of multiple databases (MEDLINE, EMBASE, and Scopus) from each database’s inception to September 2014 was performed.Study selectionEligible studies evaluated patients with primary hyperparathyroidism undergoing MIP or BNE.Data extractionReviewers working independently and in duplicate extracted data and assessed the risk of bias.Data synthesisWe identified 82 observational studies and 6 randomized trials at moderate risk of bias. Most of them reported outcomes after MIP (n = 71). Using random‐effects models to pool results across studies, the cure rate was 98 % (95 % CI 97–98 %, I2 = 10 %) with BNE and 97 % (95 % CI 96–98 %, I2 = 86 %) with MIP. Hypocalcemia occurred in 14 % (95 % CI 10–17 % I2 = 93 %) of the BNE cases and in 2.3 % (95 % CI 1.6–3.1 %, I2 = 87 %) with MIP (P < 0.001). There was a statistically significant lower risk of laryngeal nerve injury with MIP (0.3 %) than with BNE (0.9 %), but similar risk of infection (0.5 vs. 0.5 %) and mortality (0.1 vs. 0.5 %).LimitationsThe available evidence, mostly observational, is at moderate risk of bias, and limited by indirect comparisons and inconsistency for some outcomes (cure rate, hypocalcemia).ConclusionMIP and BNE are both effective surgical techniques for the treatment of primary hyperparathyroidism. The safety profile of MIP appears superior to BNE (lower rate of hypocalcemia and recurrent laryngeal nerve injury).

Dysferlinopathy is an uncommon, progressive muscular dystrophy that has a wide phenotypic variability and primarily supportive management (Nguyen et al., 2007; Narayanaswami et al., 2014). Amyloid myopathy is a distinct, rare disorder that can present similarly to inflammatory myopathies and requires a high clinical suspicion for early intervention to prolong survival. Amyloid myopathy is typically associated with other systemic manifestations of amyloidosis, but rare cases of isolated amyloid myopathy have been described (Mandl et al., 2000; Hull et al., 2001). Positive Congo red stains on tissue biopsy remain the gold standard for diagnosis (Spuler et al., 1998; Karacostas et al., 2005). A high clinical suspicion and meticulous diagnostic workup that includes novel techniques are necessary for identifying these rare disorders. We report a middle-aged man with progressive leg muscle weakness who was initially treated as having amyloid myopathy but was later diagnosed as having dysferlinopathy by Whole Exome Sequencing (WES) analysis. We also report a novel missense mutation (c.959G>C) to help correlate in any patient with presumed dysferlinopathy and to add to the already known genotype of this disorder.

Background: Up to 10% of free-hand pedicle screws are malpositioned, and 1 in 300 patients may undergo return to surgery for revision of malpositioned screws. The indications for revision of asymptomatic malpositioned screws have not been carefully examined in the literature. We sought to evaluate the threshold among spinal deformity surgeons for revision of malpositioned screws. Methods: Twelve experienced spine surgeons reviewed x-ray and computed tomographic images of 32 malpositioned pedicle screws with variable degrees of anterior, medial, and lateral breeches. The surgeons were asked whether based on the image they would revise the screw: (1) intraoperatively before rod placement; (2) intraoperatively after rod placement; (3) in clinic with an asymptomatic patient. For each scenario, we assumed stable neuromonitoring and no neurological changes. Agreement and multirater κ was calculated. Results: There was good agreement as to which screws were malpositioned (80% agreement, κ=0.703). After the rod was placed or postoperatively (scenarios 2 and 3), surgeons less frequently recommended screw revision, and there was greater variability among the surgeons’ recommendations. For return to surgery from clinic for asymptomatic screw revision, % agreement was only 65% (κ=0.477). The majority recommended revision surgery for screws which approached the dura (10/12) or the aorta (7/12 surgeons). Half of the surgeons recommended revision surgery for an asymptomatic screw if the entire screw diameter was in the canal. Revision surgery was not recommended for asymptomatic patients with screws partially violating the canal (<½ the screw diameter), malpositioned laterally in the rib head, or with small anterior cortical violations remote from a vascular structure. Conclusions: There is significant variability of opinion among surgeons regarding which malpositioned screws can be safely observed in an asymptomatic patient. Given the frequency of malpositioned screws and morbidity of surgical return to surgery, more long-term data are needed to develop practice guidelines for determining which screws require revision surgery. Level of Evidence: Level III—retrospective comparative study.

Purpose: To report flattening of a treatment-resistant retinal pigment epithelial detachment (PED) due to neovascular age-related macular degeneration after a single intravitreal injection of ziv-aflibercept (Zaltrap). Methods: A 67-year-old woman with a neovascular age-related macular degeneration–related PED was treated with intravitreal injections of bevacizumab and ranibizumab, and in combination with verteporfin photodynamic therapy, before receiving a single intravitreal injection of ziv-aflibercept (1.25 mg/0.05 mL). Results: The patient presented with a visual acuity of 20/30 in the right eye, a PED height of 581 μm, and a central macular thickness of 381 μm. She received eight intravitreal injections of bevacizumab and ranibizumab, one in combination with photodynamic therapy. The height of the PED and the central macular thickness varied over time, but 3 years later, they measured 382 μm and 418 μm, respectively. A single intravitreal injection of ziv-aflibercept resulted in a dramatic reduction in PED height to 140 μm, which was maintained 2 months later. The visual acuity remained stable, and there were no clinical signs of toxicity. Conclusion: Intravitreal ziv-aflibercept safely and effectively improved a treatment-resistant PED. Intravitreal ziv-aflibercept could become a treatment option for neovascular age-related macular degeneration in countries where aflibercept (Eylea) is not available or its cost is prohibitive, but further studies are necessary to establish efficacy and safety.

Background: The use of progressive tension sutures has been shown to be comparable to the use of abdominal drains in abdominoplasty. However, the use of barbed progressive tension sutures (B-PTSs) in deep inferior epigastric artery perforator (DIEP) flap donor-site closure has not been investigated. Methods: A retrospective chart review was performed on patients with DIEP flap reconstruction in a 3-year period at 2 institutions by 2 surgeons. Patients were compared by method of DIEP donor-site closure. Group 1 had barbed running progressive tension sutures without drain placement. Group 2 had interrupted progressive tension closure with abdominal drain placement (PTS-AD). Group 3 had closure with only abdominal drain placement (AD). Data collected included demographics, perioperative data, and postoperative outcomes. Results: Seventy-five patients underwent DIEP reconstruction (25 B-PTS, 25 PTS-AD, and 25 AD). Patient characteristics—age, body mass index, comorbidities, smoking status, and chemotherapy—were not significantly different between groups. Rate of seroma was 1.3% (B-PTS = 0%, PTS-AD = 4%, AD = 0%), wound dehiscence 16% (B-PTS = 8%, PTS-AD = 16%, AD = 24%), and umbilical necrosis 5.3% (B-PTS = 0%, PTS-AD = 0%, AD = 16%). No hematomas were observed in any patients. No statistically significant difference was found between complication rates across groups. Conclusions: Use of B-PTSs for abdominal closure after DIEP flap harvest can obviate the need for abdominal drains. Complication rates following this technique are not significantly different from closure using progressive tension suture and abdominal drain placement. This practice can prevent the use of abdominal drains, which can promote patient mobility, increase independence upon discharge, and contribute to patient satisfaction.

Purpose of review The success of LDL cholesterol (LDL-C) as a predictor of atherosclerotic cardiovascular disease and a therapeutic target is indisputable. Apolipoprotein B (apoB) is a more contemporary and physiologically relevant measure of atherogenic lipoproteins. This report summarizes recent comparisons of apoB and LDL-C as biomarkers of cardiovascular risk. Recent findings Multiple recent reports have found that LDL-C methods perform poorly at low concentrations (<70 mg/dl). Several meta-analyses from randomized controlled trials and large prospective observational studies have found that apoB and LDL-C provide equivalent information on risk of cardiovascular disease. More innovative analyses have asserted that apoB is a superior indicator of actual risk when apoB and LDL-C disagree. Summary ApoB is more analytically robust and standardized biomarker than LDL-C. Large population studies have found that apoB is at worst clinically equivalent to LDL-C and likely superior when disagreement exists. Realistically, many obstacles prevent the wide spread adoption of apoB and for now providers and their patients must weigh the costs and benefits of apoB.