Computed tomography measurements to predict need for robotic transversus abdominis release: a single institution analysis.

PURPOSE: The radiographic rectus width to hernia width ratio (RDR) has been shown to predict ability to close fascial defect without additional myofascial release in open Rives-Stoppa abdominal wall reconstruction (AWR), but it has not been studied in robotic AWR. We aimed to examine various CT measurements to determine their usability in predicting the need for transversus abdominis release (TAR) in robotic AWR. METHODS: We performed a single-center retrospective review of 137 patients with midline ventral hernias over a 5-year period who underwent elective robotic retrorectus AWR. We excluded patients with M1 or M5 hernias, lateral/flank hernias, and hybrid repairs. The CT measurements included hernia width (HW), hernia width/abdominal width ratio (HW/AW), and RDR. Univariate, multivariate and area under the curve (AUC) analyses were performed. RESULTS: 58/137 patients required TAR (32 unilateral, 26 bilateral). Patients undergoing TAR had a significantly higher average HW and HW/AW and lower RDR. Multivariate analysis revealed that prior hernia repair was independently associated with need for TAR (p = 0.03). ROC analysis and AUC values showed acceptable diagnostic ability of HW, HW/AW and RDR in predicting need for TAR. Cutoffs of RDR ≤ 2, HW/AW > 0.3, and HW > 10 cm yielded high specificity in determining need for any TAR (97.5% vs. 96.2% vs. 92.4%) or bilateral TAR (95.5% vs. 94.6% vs. 92.8%). CONCLUSION: History of prior hernia repair was a risk factor for robotic TAR. CT measurements have some predictive value in determining need for TAR in robotic AWR. Further prospective analysis is needed in this patient population.

Gut-derived acetate promotes B10 cells with antiinflammatory effects.

Autoimmune diseases are characterized by a breakdown of immune tolerance partly due to environmental factors. The short-chain fatty acid acetate, derived mostly from gut microbial fermentation of dietary fiber, promotes antiinflammatory Tregs and protects mice from type 1 diabetes, colitis, and allergies. Here, we show that the effects of acetate extend to another important immune subset involved in tolerance, the IL-10-producing regulatory B cells (B10 cells). Acetate directly promoted B10 cell differentiation from mouse B1a cells both in vivo and in vitro. These effects were linked to metabolic changes through the increased production of acetyl-coenzyme A, which fueled the TCA cycle and promoted posttranslational lysine acetylation. Acetate also promoted B10 cells from human blood cells through similar mechanisms. Finally, we identified that dietary fiber supplementation in healthy individuals was associated with increased blood-derived B10 cells. Direct delivery of acetate or indirect delivery via diets or bacteria that produce acetate might be a promising approach to restore B10 cells in noncommunicable diseases.

[11C]PBR28 MR-PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder.

Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance-positron emission tomography (MR-PET) scanner with the second-generation TSPO radiotracer [11C]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR-PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.

A cost-utility analysis of atezolizumab in the second-line treatment of patients with metastatic bladder cancer.

Background: Despite initial promising results, the IMvigor211 clinical trial failed to demonstrate an overall survival (os) benefit for atezolizumab compared with chemotherapy as second-line treatment for metastatic bladder cancer (mbc). However, given lessened adverse events (aes) and preserved quality of life (qol) with atezolizumab, there might still be investment value. To evaluate that potential value, we conducted a cost-utility analysis (cua) of atezolizumab compared with chemotherapy from the perspective of the Canadian health care payer. Methods: A partitioned survival model was used to evaluate atezolizumab compared with chemotherapy over a lifetime horizon (5 years). The base-case analysis was conducted for the intention-to-treat (itt) population, with additional scenario analyses for subgroups by IMvigor-defined PD-L1 status. Health outcomes were evaluated through life-year gains and quality-adjusted life-years (qalys). Cost estimates in 2018 Canadian dollars for systemic treatment, aes, and end-of-life care were incorporated. The incremental cost-effectiveness ratio (icer) was used to compare treatment strategies. Parameter and model uncertainty were assessed through sensitivity and scenario analyses. Per Canadian guidelines, cost and effectiveness were discounted at 1.5%. Results: For the itt population, the expected qalys for atezolizumab and chemotherapy were 0.75 and 0.56, with expected costs of $90,290 and $8,466 respectively. The resultant icer for atezolizumab compared with chemotherapy was $430,652 per qaly. Scenario analysis of patients with PD-L1 expression levels of 5% or greater led to a lower icer ($334,387 per qaly). Scenario analysis of observed compared with expected benefits demonstrated a higher icer, with a shorter time horizon ($928,950 per qaly). Conclusions: Despite lessened aes and preserved qol, atezolizumab is not considered cost-effective for the second-line treatment of mbc.

Feeding practices of pre-school children and associated factors in Kathmandu, Nepal.

BACKGROUND: In developing countries such as Nepal, many children aged below 3 years do not grow at a sufficiently high rate and are vulnerable to micronutrient deficiencies (e.g. vitamin A). Challenges to child nutrition can result from poverty, unhealthy traditional practices, inadequate caring and feeding practices. The present study aimed to assess the feeding practices of pre-school children and their associated factors. METHODS: A cross-sectional study was carried out in pre-schools located in Kathmandu district between February and March 2018. Three levels in terms of price range (lower, medium and higher level) of pre-schools were selected to reach the mothers of children aged ≤3 years. A structured questionnaire was administered to 145 mothers. Descriptive analyses were conducted to observe the characteristics of the population. Multinomial logistic regression analyses were performed to identify the association for the factors of mothers' perception of their current feeding practices. RESULTS: We found that dal-bhat/jaulo was a common complementary food irrespective of socio-economic background. Interestingly, mothers who had received a higher education were significantly less likely to change their feeding practices (odds ratio = 0.118, confidence interval = 0.01-0.94). The mothers that fed a higher quantity porridge to their children showed a high willingness to change the feeding practices. CONCLUSIONS: Poor feeding practices are still an important public health problem in Nepal and were observed to be associated with low socio-economic status, unawareness and a lack of knowledge towards dietary diversity combined with strong beliefs related to social forces and cultures.

Metastatic colorectal cancer: therapeutic options for treating refractory disease.

Therapeutic options for chemorefractory metastatic colorectal cancer (mcrc) have significantly expanded since 2009. The oral targeted therapies regorafenib and trifluridine/tipiracil have been established to be efficacious and safe in patients with mcrc who have progressed beyond 2 or more lines of chemotherapy. Evidence for the use of immunotherapy in a subgroup of this patient population is also encouraging, particularly in patients with mcrc that exhibits high microsatellite instability or deficient mismatch repair. Those significant advances have led to Health Canada approval of 3 novel therapeutic options for the treatment of patients with chemorefractory mcrc. However, the limited clinical efficacy of those treatments underscores the need for ongoing development of systemic therapy options for this unique cohort of patients. Here, we review the current and emerging treatment landscape for chemorefractory mcrc.

Substance use among treatment seeking Indian adolescent girls: Are they unique?

INTRODUCTION: Substance use among adolescents is on the rise across the globe along with a diminution of gender gap observed earlier posing a huge public health burden. Unfortunately, there is a paucity of literature on adolescent substance use. The literature is even sparse about substance use among adolescent girls. The current study aims to provide a glimpse of the profile and pattern of substance use among Indian adolescent girls seeking treatment for substance use problems in a specialty addiction treatment centre in India. MATERIALS AND METHODS: This study is retrospective in design. Information regarding socio-demographics and substance use were extracted from the medical records of adolescent girls (≤ 19 years) who sought treatment for substance use problems during 2004-2018, at the adolescent clinic of a tertiary addiction treatment centre located in north India was retrieved carried out. The data was statistically analysed using SPSS. RESULTS: A total of 28 girls sought treatment during this period. The mean age of the girls was 15.89 ± 2.72 years. Most of the girls were students (6/28) or had never started working (12/28). Majority of them were coming from an urban background (89.3%) and were educated up to 10th class (85.5%). A total of 17 (60.7%) girls sought treatment for opioids use of which 11 were using illicit opioids like heroin and five (29.9%) of them reported taking opioids by injecting route primarily. History of past abstinence attempts, and treatment attempt were present in very few of them (10.7% and 14.3%). CONCLUSION: Our study suggests a distinct substance use profile of adolescent girls. There is a need for further systematic studies to assess their clinical needs.

A randomised controlled trial assessing the efficacy of co-phenylcaine nasal spray in flexible transnasal pharyngolaryngoscopy.

INTRODUCTION The aim of this study was to assess whether using co-phenylcaine nasal spray before flexible transnasal pharyngolaryngoscopy results in reduced pain and discomfort during the procedure. METHODS This was a randomised controlled trial. Eighty-four patients were randomised to receive either co-phenylcaine nasal spray or placebo nasal spray before performing transnasal flexible pharyngolaryngoscopy. Patient reported outcome measures included pain, discomfort, unpleasantness and willingness to repeat the procedure while clinician reported outcome measures comprised ease of examination and quality of view obtained during the procedure. RESULTS There was no statistically significant difference in scores for pain, discomfort, unpleasantness and willingness to repeat the procedure between the co-phenylcaine and placebo groups. On the other hand, ease of examination scores were significantly better for the co-phenylcaine group than for the placebo group. CONCLUSIONS The majority of patients do not find flexible pharyngolaryngoscopy unpleasant or painful with or without topical nasal anaesthesia. However, the spray does appear to help the examiner in completing a satisfactory assessment.

Dextran sulfate sodium-induced ulcerative colitis leads to testicular toxicity in mice: Role of inflammation, oxidative stress and DNA damage.

Ulcerative colitis is associated with an alteration in gonadal hormones and affects testicular weight in rodents. However, association of ulcerative colitis with testicular damage is not clearly known. Ulcerative colitis was induced using 5% (w/v) dextran sulfate sodium in normal drinking water for 1, 7-day cycle in short-term study and 2.5% (w/v) dextran sulfate sodium in normal drinking water for 4 cycles with 2 weeks remission period between each cycle in long-term study. Ulcerative colitis was associated with a significant increase in inflammation, oxidative stress, DNA damage in testes and sperm DNA damage and a significant decrease in the epididymal sperm count and 3ß-HSD expression. No difference was observed in the plasma testosterone levels between control and treatment groups. In the present study, ulcerative colitis was associated with testicular damage, and juvenile mice were found to be more sensitive than adult mice.

The diagnostic value of fine needle aspiration in parotid lumps.

INTRODUCTION: Fine needle aspiration (FNA) is a safe and quick method of diagnosing superficial lumps, which aids preoperative planning. However, FNA of the parotid gland has not gained the widespread acceptance noted in other head and neck lumps. The aim of this study was to determine the ability of FNA of the parotid gland to differentiate benign and malignant disease, and to determine the impact on surgical outcome. METHODS: A retrospective analysis of 201 consecutive parotid operations with preoperative FNA in a large district hospital in the UK was performed. The diagnostic characteristics were calculated for benign and malignant disease, and the impact on surgical procedure was determined. RESULTS: In identifying benign disease, FNA has a sensitivity of 85% and a specificity of 76%. In detecting malignant disease, FNA has a sensitivity and specificity of 52% and 92% respectively. A false positive on FNA was associated with a higher incidence of neck dissection. CONCLUSIONS: FNA is a useful diagnostic test. However, owing to low sensitivity, it is necessary to interpret it in the context of all other clinical information.

Association study of FUT2 (rs601338) with celiac disease and inflammatory bowel disease in the Finnish population.

Homozygosity for a nonsense mutation in the fucosyltransferase 2 (FUT2) gene (rs601338G>A) leads to the absence of ABH blood groups (FUT2 non-secretor status) in body fluids. As the secretor status has been shown to be a major determinant for the gut microbial spectrum, assumed to be important in the gut immune homeostasis, we studied the association of rs601338-FUT2 with celiac disease (CelD) and inflammatory bowel disease (IBD) in the Finnish population. Rs601338 was genotyped in CelD (n = 909), dermatitis herpetiformis (DH) (n = 116), ulcerative colitis (UC) (n = 496) and Crohn's disease (CD) (n = 280) patients and healthy controls (n = 2738). CelD showed significant genotypic [P = 0.0074, odds ratio (OR): 1.28] and recessive (P = 0.015, OR: 1.28) association with the rs601338-AA genotype. This was also found in the combined CelD+DH dataset (genotype association: P = 0.0060, OR: 1.28; recessive association: P < 0.011, OR: 1.28). The A allele of rs601338 showed nominal association with dominant protection from UC (P = 0.044, OR: 0.82) and UC+CD (P = 0.035, OR: 0.84). The frequency of non-secretors (rs601338-GG) in controls, CelD, DH, UC and CD datasets was 14.7%, 18%, 18.1%, 14.3% and 16.1%, respectively. No association was evident in the DH or CD datasets alone. In conclusion, FUT2 non-secretor status is associated with CelD susceptibility and FUT2 secretor status may also play a role in IBD in the Finnish population.

Antiplatelet drugs in elective ENT surgery.

INTRODUCTION: Oral antiplatelet drugs are increasingly being encountered in patients scheduled for elective ENT surgery. Their pre-operative cessation can have potentially serious complications in some patients, particularly those with intracoronary stents. METHODS: In order to gain an impression of current peri-operative management of patients taking antiplatelet drugs, an online survey was distributed to the Expert Panel of ENT UK, the British Association of Otolaryngologists Head and Neck Surgeons, between 13 January and 15 February 2011. RESULTS: Three hundred and three members were contacted. The response rate was 55 per cent (167 replies); 78 per cent of respondents were consultants. Results are presented in the main text. CONCLUSION AND RECOMMENDATIONS: Patients can be categorised as high or low risk, depending on their indication for taking antiplatelet drugs. Recommendations taken from the literature are given on how best to manage these two groups.

Percutaneous drainage of gastric remnant dilatation after laparoscopic Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass is a commonly performed bariatric procedure worldwide. Gastric remnant dilatation is an uncommon early complication of this procedure that can be fatal if treatment is delayed, as it can cause peritonitis and death. Herein we report a gastric bypass patient who presented with profound shock 3 months after the surgery. After resuscitation and evaluation, she was diagnosed as having a massive dilatation of gastric remnant, which we managed with percutaneous drainage.

Interaction between the ionic liquids 1-alkyl-3-methylimidazolium tetrafluoroborate and Pluronic® P103 in aqueous solution: a DLS, SANS and NMR study.

The effect of three ionic liquids (ILs) 1-alkyl 3-methyl imidazlolium tetraflouroborates (C(n)mim BF(4)n=4, 6, 8) on micellar solutions of an ethylene oxide-propylene oxide block copolymer (PEO-PPO-PEO), Pluronic® P103 was examined from scattering and NMR techniques. The ILs alter the cloud point and micelle size dependant on their alkyl chain length and the results are discussed in terms of their behavior as cosolvent/cosurfactant. Cloud point data support the hydrogen bonding between the imidazolium cation and P103 while dynamic light scattering (DLS) and small angle neutron scattering (SANS) reveal that presence of ionic liquid is not conducive to the micelle formation of P103. The selective nuclear Overhauser effect (NOESY) indicates that the PPO block of the P103 interacts with the alkyl group of the C(n)mim(+) cation by hydrophobic interaction. Through this kind of interactions, C(n)mim BF(4) and P103 can form mixed micelles. This result indicates that the presence of ILs hinders the micelle formation of P103 in solution and promotes P103 to orient at air/water interface.

Association of celiac disease genes with inflammatory bowel disease in Finnish and Swedish patients.

Some genetic loci may affect susceptibility to multiple immune system-related diseases. In the current study, we investigated whether the known susceptibility loci for celiac disease (CelD) also associate with Crohn's disease (CD) and/or ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), in Finnish patients. A total of 45 genetic markers were genotyped in a Finnish data set comprising 699 IBD patients and 2482 controls. Single-marker association with IBD and its subphenotypes was tested. A meta-analysis with a Swedish UC data set was also performed. A total of 12 single-nucleotide polymorphisms associated with CD and/or UC (P<0.05). In the subphenotype analysis, rs6974491-ELMO1 (P=0.0002, odds ratio (OR): 2.20) and rs2298428-UBE2L3 (P=5.44 × 10(-5), OR: 2.59) associated with pediatric UC and CD, respectively. In the meta-analysis, rs4819388-ICOSLG (P=0.00042, OR: 0.79) associated with UC. In the subphenotype meta-analysis, rs1738074-TAGAP (P=7.40 × 10(-5), OR: 0.61), rs6974491-ELMO1 (P=0.00052, OR: 1.73) and rs4819388-ICOSLG (P=0.00019, OR: 0.75) associated with familial UC, pediatric UC and sporadic UC, respectively. Multiple CelD risk loci also confer susceptibility for CD and/or UC in the Finnish and Swedish populations. Certain genetic risk variants may furthermore predispose an individual for developing a particular disease phenotype.

Safe and adequate placement of nasogastric tubes in the presence of a cuffed tracheostomy tube.

This case report and review of the literature aims to highlight the importance of the use of a chest radiograph to check the placement of nasogastric tubes after insertion in an awake patient with an inflated cuffed tracheostomy tube regardless of an acidic pH test.

Efficacy of isavuconazole, voriconazole and fluconazole in temporarily neutropenic murine models of disseminated Candida tropicalis and Candida krusei.

OBJECTIVES: The aim of this study was to assess the dose-response of isavuconazole, voriconazole and fluconazole in disseminated Candida tropicalis and Candida krusei infections. METHODS: Mice were immunosuppressed using either one dose [temporarily neutropenic (TN)] or two doses [persistently neutropenic (PN)] of cyclophosphamide. Treatment was started 5 h after infection with oral isavuconazole (6, 15, 30, 60, 90, 120 or 150 mg/kg equivalent active compound), intravenous voriconazole (5, 20 or 40 mg/kg plus grapefruit gavage twice daily) or oral fluconazole (15, 50 or 150 mg/kg) all administered twice daily. Kidney burden was assessed for C. tropicalis, and kidney and brain burden for C. krusei. RESULTS: Vehicle controls developed a non-lethal infection with high burdens in both models. In the TN models, isavuconazole, voriconazole and fluconazole (>50 mg/kg) reduced kidney burden compared with controls; >60 mg/kg isavuconazole and 50 mg/kg fluconazole were superior to alternative treatments (other than voriconazole 40 mg/kg). Isavuconazole (all doses) reduced brain burden (P<0.05) in the C. krusei model; fluconazole (all doses) and voriconazole (5 and 20 mg/kg) did not. In the C. krusei kidney burden model, isavuconazole 120 and 150 mg/kg and voriconazole 40 mg/kg were superior to controls and fluconazole. In the C. tropicalis model, PN isavuconazole (all doses), voriconazole (>5 mg/kg) and fluconazole (all doses) reduced kidney burden (P<0.05). Only isavuconazole (all doses) and 40 mg/kg voriconazole were effective against C. krusei in the brain, isavuconazole and voriconazole reduced tissue burden (P<0.05). Fluconazole had no significant effect on brain burden even at 150 mg/kg. CONCLUSIONS: Isavuconazole significantly reduced kidney burden in mice infected with C. tropicalis and both kidney and brain burdens in mice infected with C. krusei. Isavuconazole was as effective as voriconazole and much more effective than fluconazole at reducing brain burden.