Rectus to defect ratio for estimating the complexity of ventral hernia repair: Is it reliable for robotic surgery?

INTRODUCTION: The rectus to defect ratio (RDR) has been previously described as a metric which enables surgeons to estimate the need to perform additional myofascial release (AMR), in addition to open Rives-Stoppa retro-muscular hernia repair. We sought to validate this measurement specifically for patients undergoing robotic totally extraperitoneal (eTEP) hernia repair. METHODS: A retrospective chart review of 188 patients who underwent robotic ventral hernia repair via eTEP approach. RDR on preoperative CT was compared to the final operation rendered. The primary endpoint was the RDR's ability to predict the need for TAR to achieve fascial closure. RESULTS: Of 188 patients, 154 were repaired with rectus myofascial release, while 34 also required TAR. There was a linear decrease in the need for TAR with increasing RDR. RDR 1-1.49 (n â€‹= â€‹12) required TAR in 66.7 â€‹% of cases, RDR 1.5-1.99 (n â€‹= â€‹25) in 43.8 â€‹%, RDR 2-2.49 (n â€‹= â€‹31) in 29 â€‹%, and RDR >2.5 (n â€‹= â€‹151) in just 5.8 â€‹% CONCLUSION: The RDR accurately predicts the need for TAR to achieve fascial closure during robotic eTEP ventral hernia repair. An RDR >2.5 portends fascial closure without TAR 94.2 â€‹% of cases.

Computed tomography imaging in ventral hernia repair: can we predict the need for myofascial release?

INTRODUCTION: Currently, the need for additional myofascial release (AMR) in addition to retromuscular dissection during open Rives-Stoppa hernia repair is determined intraoperatively based on the discretion of the surgeon. We developed a novel method to objectively predict the need for AMR preoperatively using computed tomography (CT)-measured rectus width to hernia width ratio (RDR). METHODS: A retrospective chart review of all patients who underwent open retro-muscular mesh repair of midline ventral hernia between August 1, 2007 and February 1, 2018, who had a preoperative CT scan within 1 year prior to their operation. The primary endpoint was the ability of the defect ratio to predict the need for AMR in pursuit of fascial closure. The secondary endpoint was the ability of Component Separation Index (CSI) to predict the need for AMR to obtain fascial closure. RESULTS: Of 342 patients, 208 repaired with rectus abdominis release alone (RM group), while 134 required AMR (RM + group). An RDR of > 1.34 on area under the curve analysis predicted the need for AMR with 77.6% accuracy. There was a linear decrease in the need for AMR with increasing RDR: RDR < 1 required AMR in 78.8% of cases, RDR 1.1-1.49 in 52%, RDR 1.5-1.99 in 32.1%, and RDR > 2 in just 10.8%. Similarly, CSI > 0.146 predicted the need for AMR with 76.3% accuracy on area under the curve analysis. CONCLUSION: The RDR is a practical and reliable tool to predict the ability to close the defect during open Rives-Stoppa ventral hernia repair without AMR. An RDR of > 2 portends fascial closure with rectus abdominis myofascial release alone in 90% of cases.

Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial.

BACKGROUND: We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. METHODS: We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. RESULTS: Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. CONCLUSIONS: Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. CLINICAL TRIALS REGISTRATION: NCT03341767.

Prophylactic mesh augmentation using permanent synthetic mesh: outcomes of keyhole and Stapled Ostomy Reinforcement with Retromuscular Mesh techniques.

INTRODUCTION: Parastomal hernias (PSH) are the most common complication of stoma creation and can cause significant morbidity. We present a consecutive series of patients receiving prophylactic mesh augmentation (PMA) for prevention of PSH. METHODS: This retrospective review evaluates the efficacy and outcomes of PMA for PSH prevention, and retrospectively compares traditional keyhole PMA (tPMA) (n = 28) with a prophylactic Stapled Ostomy Reinforcement with Retromuscular Mesh technique (pSTORRM) (n = 24). RESULTS: PMA was performed in 52 cases between January 2015 and July 2018. All cases used a large-pore, non-coated, mid-weight polypropylene mesh placed in the retrorectus space. With a median follow-up of 16 mos, parastomal hernia was confirmed in 11.5% (n = 6), 5 of whom were symptomatic. patient-reported outcomes (PRO) indicated 6 additional patients with symptoms associated with PSH without clinical or radiographic confirmation. Patients had similar comorbidities and operative characteristics between tPMA and pSTORRM techniques, and no difference in a median follow-up. pSTORRM patients had fewer surgical site infections (8.3 vs 32.1%; p = 0.046) and occurrences (12.5 vs 46.4%; p = 0.015), and lower rate of PSH, though not statistically significant (4.2 vs 17.9%; p = 0.195). CONCLUSION: Permanent synthetic mesh placed as a sublay in the retromuscular space is safe and appears to decrease the risk of PSH formation after the creation of permanent stomas. A stapled technique may provide advantages over a traditional keyhole technique.

Adult-onset ganglioneuroblastoma of the posterior mediastinum with osseous metastasis.

Ganglioneuroblastomas are a member of the neuroblastic family of tumors most commonly seen in children but they may also occur in adults. Ganglioneuroblastomas have metastatic potential and, like other neuroblastic tumors, osseous metastasis is possible. Imaging features of ganglioneuroblastomas tend to be variable. We describe a case of an adult female who developed a ganglioneuroblastoma of the posterior mediastinum that metastasized to the thoracolumbar spine, highlighting rarely documented osseous metastasis.

Measurement of serum zinc concentration in ruminants: a comparison of results from standard serum and specific trace element collection tubes.

Aims: To evaluate agreement between the concentration of Zn in serum from samples collected from cattle and sheep into standard collection tubes for serum and from samples collected into tubes developed for trace element measurement. Methods: Eighty-eight animals (78 cattle and 10 sheep) on eight farms had paired blood samples collected into standard serum and trace element vacutainers. The paired samples were submitted the same day to the laboratory to be tested for the concentration of Zn in serum using atomic absorption spectrophotometry. The agreement between the paired results was then assessed using limits of agreement analysis. On one farm an additional 10 pairs of samples was taken from the same animals; this second set of paired samples was refrigerated for 48 hours prior to laboratory submission to identify the impact of delaying submission on the apparent concentration of Zn in serum. Results: The limits of agreement analysis found no evidence of a systematic difference between Zn concentrations in serum collected into standard serum tubes and into trace element tubes as neither the intercept nor the slope on the mean-difference plot were significantly different from zero. The SD of the difference between results increased as the concentration of Zn increased, so at the lowest Zn concentration reported in this study (6.9 µmol/L) the limits of agreement were ±1.07 µmol/L, while at the highest (23.5 µmol/L) they were ±3.39 µmol/L. Refrigerating the sample (as whole blood) for 48 hours prior to submission increased the apparent concentration of Zn in serum in both standard serum tubes and trace element tubes by 1.3 µmol/L (95% CI = 0.75-1.85). Conclusions: There was no evidence that the concentration of Zn in serum from standard serum tubes were artificially elevated. In contrast, delaying sample submission by 48 hours did elevate Zn concentrations. Clinical relevance: While these data apply only to the batch of vacutainers used in this study, there is unlikely to be much between batch variation in the potential for contamination. Thus these results suggest that monitoring zinc status in ruminants, by measuring the concentration of Zn in serum from samples collected into standard serum tubes does not result in clinically relevant alterations in Zn concentration compared to using specific trace element tubes. However delaying submission to the laboratory may result in significantly elevated concentrations of Zn in serum so should be avoided.

A Novel Piperazine-Based Drug Lead for Cryptosporidiosis from the Medicines for Malaria Venture Open-Access Malaria Box.

Cryptosporidiosis causes life-threatening diarrhea in children under the age of 5 years and prolonged diarrhea in immunodeficient people, especially AIDS patients. The standard of care, nitazoxanide, is modestly effective in children and ineffective in immunocompromised individuals. In addition to the need for new drugs, better knowledge of drug properties that drive in vivo efficacy is needed to facilitate drug development. We report the identification of a piperazine-based lead compound for Cryptosporidium drug development, MMV665917, and a new pharmacodynamic method used for its characterization. The identification of MMV665917 from the Medicines for Malaria Venture Malaria Box was followed by dose-response studies, in vitro toxicity studies, and structure-activity relationship studies using commercial analogues. The potency of this compound against Cryptosporidium parvum Iowa and field isolates was comparable to that against Cryptosporidium hominis Furthermore, unlike nitazoxanide, clofazimine, and paromomycin, MMV665917 appeared to be curative in a NOD SCID gamma mouse model of chronic cryptosporidiosis. MMV665917 was also efficacious in a gamma interferon knockout mouse model of acute cryptosporidiosis. To determine if efficacy in this mouse model of chronic infection might relate to whether compounds are parasiticidal or parasitistatic for C. parvum, we developed a novel in vitro parasite persistence assay. This assay suggested that MMV665917 was parasiticidal, unlike nitazoxanide, clofazimine, and paromomycin. The assay also enabled determination of the concentration of the compound required to maximize the rate of parasite elimination. This time-kill assay can be used to prioritize early-stage Cryptosporidium drug leads and may aid in planning in vivo efficacy experiments. Collectively, these results identify MMV665917 as a promising lead and establish a new method for characterizing potential anticryptosporidial agents.

shapecoder: a new method for visual quantification of body mass index in young children.

BACKGROUND: Few tools exist to quantify body mass index visually. OBJECTIVE: To examine the inter-rater reliability and validity (sensitivity and specificity for overweight/obesity and obesity) of a three-dimensional visual rating system to quantify body mass index (BMI) in young children. METHODS: Children (n = 242, mean age 5.9 years, 50.0% male; 40.5% overweight/ obese) participated in a videotaped protocol and weight and height were measured. Research staff applied a novel three-dimensional computer-based figure rating system (shapecoder) to the child's videotaped image. Inter-rater reliability was calculated, as well as correlation with measured body mass index (BMI) and sensitivity, specificity, positive predictive value and negative predictive value for overweight/obesity and obesity. RESULTS: Inter-rater reliability was excellent (intraclass correlation coefficient = 0.98). The correlation of shapecoder-generated BMI with measured BMI was 0.89. For overweight/obesity, the sensitivity, specificity, positive predictive value and negative predictive value were 62%, 97%, 94% and 79% respectively. For obesity, these values were 65%, 99%, 97% and 92% respectively. CONCLUSION: shapecoder provides a method to quantify child BMI from video images with high inter-rater reliability, fair sensitivity and good specificity for overweight/obesity and obesity. The approach offers an improvement over existing two-dimensional rating scales for BMI.

Otolith shape lends support to the sensory drive hypothesis in rockfishes.

The sensory drive hypothesis proposes that environmental factors affect both signalling dynamics and the evolution of signals and receivers. Sound detection and equilibrium in marine fishes are senses dependent on the sagittae otoliths, whose morphological variability appears intrinsically linked to the environment. The aim of this study was to understand if and which environmental factors could be conditioning the evolution of this sensory structure, therefore lending support to the sensory drive hypothesis. Thus, we analysed the otolith shape of 42 rockfish species (Sebastes spp.) to test the potential associations with the phylogeny, biological (age), ecological (feeding habit and depth distribution) and biogeographical factors. The results showed strong differences in the otolith shapes of some species, noticeably influenced by ecological and biogeographical factors. Moreover, otolith shape was clearly conditioned by phylogeny, but with a strong environmental effect, cautioning about the use of this structure for the systematics of rockfishes or other marine fishes. However, our most relevant finding is that the data supported the sensory drive hypothesis as a force promoting the radiation of the genus Sebastes. This hypothesis holds that adaptive divergence in communication has significant influence relative to other life history traits. It has already been established in Sebastes for visual characters and organs; our results showed that it applies to otolith transformations as well (despite the clear influence of feeding and depth), expanding the scope of the hypothesis to other sensory structures.

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.

Water quality survey of Mississippi's Upper Pearl River.

Surface water samples were collected from May 2002 through May 2003 at seven locations within the Upper Pearl River Basin (UPRB) in east-central Mississippi to assess levels of pesticide impairment in the watershed. Depth-integrated samples were collected at three sites from September 2001 through January 2003 for total dissolved solid (TDS) analysis. Samples were extracted via Solid Phase Extraction (SPE) and analyzed for fifteen pesticides: triclopyr, 2,4-D, tebuthiuron, simazine, atrazine, metribuzin, alachlor, metolachlor, cyanazine, norflurazon, hexazinone, pendimethalin, diuron, fluometuron, and the dichlorodiphenyltrichloroethane (DDT) degradation product p,p'-DDE. Of the analyzed compounds, hexazinone was detected in 94% of the samples, followed by metolachlor (76%), tebuthiuron (48%), and atrazine (47%). Metribuzin was detected in 6% of the samples and was the least detected compound of those analyzed. Sediment concentrations ranged from 20.64 mg/L at Burnside to 42.20mg/L at Carthage, which also had the highest cumulative total sediment concentration at 4,009 mg/L.

Distribution and severity of weakness among patients with polymyositis, dermatomyositis and juvenile dermatomyositis.

OBJECTIVE: To describe the distribution and severity of muscle weakness using manual muscle testing (MMT) in 172 patients with PM, DM and juvenile DM (JDM). The secondary objectives included characterizing individual muscle group weakness and determining associations of weakness with functional status and myositis characteristics in this large cohort of patients with myositis. METHODS: Strength was assessed for 13 muscle groups using the 10-point MMT and expressed as a total score, subscores based on functional and anatomical regions, and grades for individual muscle groups. Patient characteristics and secondary outcomes, such as clinical course, muscle enzymes, corticosteroid dosage and functional status were evaluated for association with strength using univariate and multivariate analyses. RESULTS: A gradient of proximal weakness was seen, with PM weakest, DM intermediate and JDM strongest among the three myositis clinical groups (P < or = 0.05). Hip flexors, hip extensors, hip abductors, neck flexors and shoulder abductors were the muscle groups with the greatest weakness among all three clinical groups. Muscle groups were affected symmetrically. CONCLUSIONS: Axial and proximal muscle impairment was reflected in the five weakest muscles shared by our cohort of myositis patients. However, differences in the pattern of weakness were observed among all three clinical groups. Our findings suggest a greater severity of proximal weakness in PM in comparison with DM.

Failure of aneurysm sac shrinkage after endovascular repair; the effect of mural calcification.

AIM: To evaluate the effect of abdominal aortic aneurysm wall calcification on subsequent sac shrinkage after endovascular repair. MATERIALS AND METHODS: Seventy-three patients underwent endovascular aneurysm repair. The degree of sac wall calcification on pre-procedural computed tomography (CT) examination was graded from 1 to 4 according to the degree of circumferential involvement. On follow-up CT imaging, the maximum transverse diameter (MTD) of the sac was recorded, as well as the presence or absence of endoleak. In those patients with a non-shrinking aneurysm, but no CT evidence of endoleak, contrast-enhanced ultrasound (USS) was performed. Any patient with an endoleak, however diagnosed, was excluded from the study. Kruskal-Wallis and Spearman's rank correlation coefficient testing was applied to compare the degree of calcification and change in MTD. RESULTS: Sixty-three pre-procedural CT images were available for calcification grading. Six of this group had endoleaks resulting in 57 sets of data being available for the study. A reduction in MTD occurred in 68.25% of these patients by 1 year post-procedure. Our figures show aortic calcification is inversely associated with MTD reduction at 6 months (p = 0.01), 1 year (p = 0.05) and 2 years (p = 0.05). CONCLUSION: This study indicates that the degree of aortic wall calcification is significant in predicting MTD reduction post-endovascular repair. The possible mechanisms and implications of this are discussed.

Common treatment of polycystic ovarian syndrome and major depressive disorder: case report and review.

We present the case of a young woman with treatment-resistant major depression, who presented to the Mood Disorders Clinic with a Hamilton Psychiatric Rating Scale for Depression (HAM-D-21) score of 28, after a year-long treatment with Effexor-XR. The patient also had untreated Polycystic Ovarian Syndrome (PCOS). The resolution of her depressive symptoms resulted from the treatment for PCOS with metformin and spironolactone. The patient remained euthymic 5 months after discontinuation of the antidepressant while continuing therapy for PCOS. We briefly overview of the pertinent literature of the pathophysiology of PCOS and affective disorders, highlighting an overlap in phenotypical presentations between these two disorders. Dysregulation of the hypothalamo-pituitary axis and various end organ systems are implicated in both PCOS and affective disorders. As such, several clinical and biochemical markers are common to both disorders, namely insulin resistance, obesity, and hyperandrogenism. In addition, these metabolic abnormalities are interrelated, causing women with PCOS or affective disorders to get caught in a "vicious cycle" of hormonal dysregulation. The case report presented here illustrates how treatment of symptoms such as insulin resistance and hyperandrogenism can lead to remission of major depressive disorder and PCOS. We suggest that through treatment of underlying metabolic defects, both the mood of the patient and the metabolic condition of PCOS can be assisted.

Synovial sarcoma in the retropharyngeal space.

Synovial sarcoma is an aggressive mesenchymal tumour, rarely occurring in the head and neck. Management guidelines are by extrapolation of management of sarcomas in the extremities. We present a case involving the retropharyngeal space in a 20-year-old male. Analysis of more data on head and neck synovial sarcoma is necessary to make meaningful management recommendations.

Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia.

Familial hypertriglyceridemia (FHTG), a disease characterized by elevated plasma very low density lipoprotein triglyceride levels, has been associated with impaired intestinal absorption of bile acids. The aim of this study was to test the hypothesis that defects in the active ileal absorption of bile acids are a primary cause of FHTG. Single-stranded conformation polymorphism analysis was used to screen the ileal Na(+)/bile acid cotransporter gene (SLC10A2) for FHTG-associated mutations. Analysis of 20 hypertriglyceridemic patients with abnormal bile acid metabolism revealed 3 missense mutations (V98I, V159I, and A171S), a frame-shift mutation (646insG) at codon 216, and 4 polymorphisms in the 5' flanking sequence of SLC10A2. The SLC10A2 missense mutations and 5' flanking sequence polymorphisms were not correlated with bile acid production or turnover in the hypertriglyceridemic patients and were equally prevalent in the unaffected control subjects. In transfected COS cells, the V98I, V159I, and A171S isoforms all transported bile acids similar to the wild-type SLC10A2. The 646insG frame-shift mutation abolished bile acid transport activity in transfected COS cells but was found in only a single FHTG patient. These findings indicate that the decreased intestinal bile acid absorption in FHTG patients is not commonly associated with inherited defects in SLC10A2.