Association between increased Subcutaneous Adipose Tissue Radiodensity and cancer mortality: Automated computation, comparison of cancer types, gender, and scanner bias.

PURPOSE: Body composition analysis using computed tomography (CT) is proposed as a predictor of cancer mortality. An association between subcutaneous adipose tissue radiodensity (SATr) and cancer-specific mortality was established, while gender effects and equipment bias were estimated. METHODS: 7,475 CT studies were selected from 17 cohorts containing CT images of untreated cancer patients who underwent follow-up for a period of 2.1-118.8 months. SATr measures were collected from published data (n = 6,718) or calculated according to CT images using a deep-learning network (n = 757). The association between SATr and mortality was ascertained for each cohort and gender using the p-value from either logistic regression or ROC analysis. The Kruskal-Wallis test was used to analyze differences between gender distributions, and automatic segmentation was evaluated using the Dice score and five-point Likert quality scale. Gender effect, scanner bias and changes in the Hounsfield unit (HU) to detect hazards were also estimated. RESULTS: Higher SATr was associated with mortality in eight cancer types (p < 0.05). Automatic segmentation produced a score of 0.949 while the quality scale measurement was good to excellent. The extent of gender effect was 5.2 HU while the scanner bias was 10.3 HU. The minimum proposed HU change to detect a patient at risk of death was between 5.6 and 8.3 HU. CONCLUSIONS: CT imaging provides valuable assessments of body composition as part of the staging process for several cancer types, saving both time and cost. Gender specific scales and scanner bias adjustments should be carried out to successfully implement SATr measures in clinical practice.

A new oral model of free fatty acid kinetics to assess lipolysis in subjects with and without type 2 diabetes.

Assessing free fatty acids (FFAs) kinetics and the role of insulin and glucose on FFA lipolysis and disposal may improve our understanding of the pathogenesis of type 2 diabetes (T2D). Some models have been proposed to describe FFA kinetics during an intravenous glucose tolerance test and only one during an oral glucose tolerance test. Here, we propose a model of FFA kinetics during a meal tolerance test and use it to assess possible differences in postprandial lipolysis in individuals with type 2 diabetes (T2D) and individuals with obesity without type 2 diabetes (ND). We studied 18 obese ND and 16 T2D undergoing three meal tolerance tests (MTT) on three occasions (breakfast, lunch, and dinner). We used plasma glucose, insulin, and FFA concentrations collected at breakfast to test a battery of models and selected the best one based on physiological plausibility, ability to fit the data, precision of parameter estimates, and the Akaike parsimony criterion. The best model assumes that the postprandial suppression of FFA lipolysis is proportional to the above basal insulin, while FFA disposal is proportional to FFA concentration. It was used to compare FFA kinetics in ND and T2D along the day. The maximum lipolysis suppression occurred significantly earlier in ND than T2D (39 ± 6 min vs. 102 ± 13 min, 36 ± 4 min vs. 78 ± 11 min, and 38 ± 6 min vs. 84 ± 13 min, P < 0.01, at breakfast, lunch, and dinner, respectively), making lipolysis significantly lower in ND than T2D. This is mainly attributable to the lower insulin concentration in the second group. This novel FFA model allows to assess lipolysis and insulin antilipolytic effect in postprandial conditions.NEW & NOTEWORTHY In this study, we propose a new mathematical model able to quantify postprandial FFA kinetics and adipose tissue insulin sensitivity in both subjects with obesity without type 2 diabetes (ND) and subjects with type 2 diabetes (T2D). Results show that the slower postprandial suppression of lipolysis in T2D contributes to the higher free fatty acid (FFA) concentration that, in turn, may contribute to hyperglycemia.

Gluclas: A software for computer-aided modulation of glucose infusion in glucose clamp experiments.

BACKGROUND AND OBJECTIVE: The glucose clamp (GC) is an experimental technique for assessing several aspects of glucose metabolism. In these experiments, investigators face the non-trivial challenge of accurately adjusting the rate of intravenous glucose infusion to drive subjects' blood glucose (BG) concentration towards a desired plateau level. In this work we present Gluclas, an open-source software to support researchers in the modulation of glucose infusion rate (GIR) during GC experiments. METHODS: Gluclas uses a proportional-integrative-derivative controller to provide GIR suggestions based on BG measurements. The controller embeds an anti-wind-up scheme to account for actuator physical limits and suitable corrections of control action to accommodate for possible sampling jitter due to manual measurement and actuation. The software also provides a graphic user interface to increase its usability. A preliminary validation of the controller is performed for different clamp scenarios (hyperglycemic, euglycemic, hypoglycemic) on a simulator of glucose metabolism in healthy subjects, which also includes models of measurement error and sampling delay for increased realism. In silico trials are performed on 50 virtual subjects. We also report the results of the first in-vivo application of the software in three subjects undergoing a hypoglycemic clamp. RESULTS: In silico, during the plateau period, the coefficient of variation (CV) is in median below 5% for every protocol, with 5% being considered the threshold for sufficient quality. In terms of median [5th percentile, 95th percentile], average BG level during the plateau period is 12.18 [11.58 - 12.53] mmol/l in the hyperglycemic clamp (target: 12.4 mmol/), 4.92 [4.51 - 5.14] mmol/l in the euglycemic clamp (target: 5.5 mmol/) and 2.38 [2.33 - 2.64] in the hypoglycemic clamp (target: 2.5 mmol/). Results in vivo are consistent with those obtained in silico during the plateau period: average BG levels are between 2.56 and 2.68 mmol/l (target: 2.5 mmol/l); CV is below 5% for all three experiments. CONCLUSIONS: Gluclas offered satisfactory control for tested GC protocols. Although its safety and efficacy need to be further validated in vivo, this preliminary validation suggest that Gluclas offers a reliable and non-expensive solution for reducing investigator bias and improving the quality of GC experiments.

Peripapillary and optic nerve head vessel density of glaucoma and healthy subjects from Afro-Caribbean and European descent: A pilot study.

PURPOSE: To compare the peripapillary and optic nerve head vessel density (PP-ONH VD) between glaucoma patients (all, early, moderated, and advanced) and healthy subjects of Afro-Caribbean descent (AD) and European descent (ED). METHODS: This was a cross-sectional study. One eye was evaluated in 90 subjects, including 66 glaucoma patients and 24 healthy subjects, who underwent PP-ONH VD imaging using SPECTRALIS® Optical Coherence Tomography Angiography (OCT-A). We analysed the superficial vascular complex using the AngioTool version 0.6a software. The correlation between the PP-ONH VD and visual field mean deviation (MD) was evaluated using a scatter plot and Spearman's rho correlation coefficient. RESULTS: Among the healthy subjects, the AD group had a lower superficial PP-ONH VD [43.29±3.25% (mean±standard deviation)] than the ED group (46.06±1.75%) (P=0.016). Overall, superficial PP-ONH VD did not show any significant differences between the total AD and ED glaucoma patients or in the subgroup analyses (early/moderate/advanced) (AD: 32.73±6.70%, 37.11±5.72%, 32.48±5.73%, 27.76±4.74%, respectively; ED: 33.94±6.89%, 38.52±3.82%, 35.56±4.18%; 27.65±6.31%, respectively) (P>0.05 for all). A strong, statistically significant correlation was established between vessel density and mean deviation among AD and ED glaucoma patients (r=0.709 and r=0.704, respectively) (P<0.001 for both). CONCLUSION: This pilot study shows that healthy subjects of AD had lower peripapillary and optic nerve head superficial vessel density than healthy subjects of ED, but no significant differences were found between AD and ED glaucoma groups (all, early, moderate, or advanced).

A PID Control Algorithm for a Post-Prandial Hypoglycemic Clamp Study.

Post-prandial hypoglycemia occurs 2-5 hours after food intake, in not only insulin-treated patients with diabetes but also other metabolic disorders. For example, postprandial hypoglycemia is an increasingly recognized late metabolic complication of bariatric surgery (also known as PBH), particularly gastric bypass. Underlying mechanisms remain incompletely understood to date. Besides excessive insulin exposure, impaired counter-regulation may be a further pathophysiological feature. To test this hypothesis, we need standardized postprandial hypoglycemic clamp procedures in affected and unaffected individuals allowing to reach identical predefined postprandial hypoglycemic trajectories. Generally, in these experiments, clinical investigators manually adjust glucose infusion rate (GIR) to clamp blood glucose (BG) to a target hypoglycemic value. Nevertheless, reaching the desired target by manual adjustment may be challenging and possible glycemic undershoots when approaching hypoglycemia can be a safety concern for patients. In this study, we developed a PID algorithm to assist clinical investigators in adjusting GIR to reach the predefined trajectory and hypoglycemic target. The algorithm is developed in a manual mode to permit the clinical investigator to interfere. We test the controller in silico by simulating glucose-insulin dynamics in PBH and healthy nonsurgical individuals. Different scenarios are designed to test the robustness of the algorithm to different sources of variability and to errors, e.g. outliers in the BG measurements, sampling delays or missed measurements. The results prove that the PID algorithm is capable of accurately and safely reaching the target BG level, on both healthy and PBH subjects, with a median deviation from reference of 2.8% and 2.4% respectively.Clinical relevance- This control algorithm enables standardized, accurate and safe postprandial hypoglycemic clamps, as evidenced in silico in PBH patients and controls.

Microbiota-associated risk factors for asymptomatic gut colonisation with multi-drug-resistant organisms in a Dutch nursing home.

BACKGROUND: Nursing home residents have increased rates of intestinal colonisation with multidrug-resistant organisms (MDROs). We assessed the colonisation and spread of MDROs among this population, determined clinical risk factors for MDRO colonisation and investigated the role of the gut microbiota in providing colonisation resistance against MDROs. METHODS: We conducted a prospective cohort study in a Dutch nursing home. Demographical, epidemiological and clinical data were collected at four time points with 2-month intervals (October 2016-April 2017). To obtain longitudinal data, faecal samples from residents were collected for at least two time points. Ultimately, twenty-seven residents were included in the study and 93 faecal samples were analysed, of which 27 (29.0%) were MDRO-positive. Twelve residents (44.4%) were colonised with an MDRO at at least one time point throughout the 6-month study. RESULTS: Univariable generalised estimating equation logistic regression indicated that antibiotic use in the previous 2 months and hospital admittance in the previous year were associated with MDRO colonisation. Characterisation of MDRO isolates through whole-genome sequencing revealed Escherichia coli sequence type (ST)131 to be the most prevalent MDRO and ward-specific clusters of E. coli ST131 were identified. Microbiota analysis by 16S rRNA gene amplicon sequencing revealed no differences in alpha or beta diversity between MDRO-positive and negative samples, nor between residents who were ever or never colonised. Three bacterial taxa (Dorea, Atopobiaceae and Lachnospiraceae ND3007 group) were more abundant in residents never colonised with an MDRO throughout the 6-month study. An unexpectedly high abundance of Bifidobacterium was observed in several residents. Further investigation of a subset of samples with metagenomics showed that various Bifidobacterium species were highly abundant, of which B. longum strains remained identical within residents over time, but were different between residents. CONCLUSIONS: Our study provides new evidence for the role of the gut microbiota in colonisation resistance against MDROs in the elderly living in a nursing home setting. Dorea, Atopobiaceae and Lachnospiraceae ND3007 group may be associated with protection against MDRO colonisation. Furthermore, we report a uniquely high abundance of several Bifidobacterium species in multiple residents and excluded the possibility that this was due to probiotic supplementation.

Development of High-Specificity Fluorescent Probes to Enable Cannabinoid Type 2 Receptor Studies in Living Cells.

Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment of numerous conditions, including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite the significance of this receptor, researchers lack reliable tools to address questions concerning the expression and complex mechanism of CB2R signaling, especially in cell-type and tissue-dependent contexts. Herein, we report for the first time a versatile ligand platform for the modular design of a collection of highly specific CB2R fluorescent probes, used successfully across applications, species, and cell types. These include flow cytometry of endogenously expressing cells, real-time confocal microscopy of mouse splenocytes and human macrophages, as well as FRET-based kinetic and equilibrium binding assays. High CB2R specificity was demonstrated by competition experiments in living cells expressing CB2R at native levels. The probes were effectively applied to FACS analysis of microglial cells derived from a mouse model relevant to Alzheimer's disease.

Urethroscrotal fistula complicating large spermatocele in a male ketamine abuser: A case report.

Ketamine related urinary tract complications were first reported in Hong Kong since 2007. The current case report describes a 37 years old male with long history of ketamine abuse, renal impairment, hypertension and HCV hepatitis, presented to us with insidious onset of painful scrotal swelling post bilateral nephrectomy, prostate and seminal vesicle preserving cystectomy. Radiological imaging and intraoperative finding revealed that it was a large spermatocele with urethroscrotal fistula, which was likely due to urethra stricture. The review of literature showed no guidelines for treatment, a symptoms based and multidisciplinary team approach is recommended.

Differential regulation of the immune system in a brain-liver-fats organ network during short-term fasting.

OBJECTIVE: Fasting regimens can promote health, mitigate chronic immunological disorders, and improve age-related pathophysiological parameters in animals and humans. Several ongoing clinical trials are using fasting as a potential therapy for various conditions. Fasting alters metabolism by acting as a reset for energy homeostasis, but the molecular mechanisms underlying the beneficial effects of short-term fasting (STF) are not well understood, particularly at the systems or multiorgan level. METHODS: We performed RNA-sequencing in nine organs from mice fed ad libitum (0 h) or subjected to fasting five times (2-22 h). We applied a combination of multivariate analysis, differential expression analysis, gene ontology, and network analysis for an in-depth understanding of the multiorgan transcriptome. We used literature mining solutions, LitLab™ and Gene Retriever™, to identify the biological and biochemical terms significantly associated with our experimental gene set, which provided additional support and meaning to the experimentally derived gene and inferred protein data. RESULTS: We cataloged the transcriptional dynamics within and between organs during STF and discovered differential temporal effects of STF among organs. Using gene ontology enrichment analysis, we identified an organ network sharing 37 common biological pathways perturbed by STF. This network incorporates the brain, liver, interscapular brown adipose tissue, and posterior-subcutaneous white adipose tissue; hence, we named it the brain-liver-fats organ network. Using Reactome pathways analysis, we identified the immune system, dominated by T cell regulation processes, as a central and prominent target of systemic modulations during STF in this organ network. The changes we identified in specific immune components point to the priming of adaptive immunity and parallel the fine-tuning of innate immune signaling. CONCLUSIONS: Our study provides a comprehensive multiorgan transcriptomic profiling of mice subjected to multiple periods of STF and provides new insights into the molecular modulators involved in the systemic immunotranscriptomic changes that occur during short-term energy loss.

Inducing remission of Type 2 diabetes in the Caribbean: findings from a mixed methods feasibility study of a low-calorie liquid diet-based intervention in Barbados.

AIM: In a high proportion of people with recently diagnosed Type 2 diabetes, a short (2-3-month) low-calorie diet is able to restore normal glucose and insulin metabolism. The aim of this study was to determine the feasibility of this approach in Barbados. METHODS: Twenty-five individuals with Type 2 diabetes diagnosed within past 6 years, not on insulin, BMI ≥ 27 kg/m2 were recruited. Hypoglycaemic medication was stopped on commencement of the 8-week liquid (760 calorie) diet. Insulin response was assessed in meal tests at baseline, 8 weeks and 8 months. Semi-structured interviews, analysed thematically, explored participants' experiences. 'Responders' were those with fasting plasma glucose (FPG) < 7 mmol/l at 8 weeks. RESULTS: Ten men and 15 women (mean age 48, range 26-68 years) participated. Mean (sd) BMI was 34.2 kg/m2 (6.0); FPG 9.2 mmol/l (2.2). Mean weight loss at 8 weeks and 8 months was 10.1 kg [95% confidence interval (CI) 8.1, 12.0] and 8.2 kg (95% CI 5.8, 10.6); FPG was lower by 2.2 mmol/l (95% CI 1.2, 3.2) and 1.7 mmol/l (95% CI 0.8, 2.7) respectively. Nine of 11 (82%) of those who lost ≥ 10 kg were 'responders' compared with 6 of 14 (43%) who lost < 10 kg (P = 0.048). The 30-min insulin increment was higher in responders at baseline and follow-up (P ≤ 0.01). A food culture based on starchy foods and pressures to eat large amounts at social events were among the challenges identified by participants. CONCLUSIONS: The feasibility of this approach to weight loss and diabetes remission in a predominantly black population in Barbados was demonstrated.

Case of nephropulmonary fistula and literature review.

From the literature, the managements for nephropulmonary fistula were variable. We would like to present our case and review the literature for the best method of care. The common features were 1) infected kidney; 2) ipsilateral lower lobe pneumonia or pleural effusion; 3) sputum and urine culture growing the same organism. Renal gaseous content may not be present on x-ray or even CT scan. The choice of management for the nephropulmonary fistula was diverse. However, conservative managements including antibiotics, endourological procedures for stone clearance, percutaneous drainage were not successful. Nephrectomies were required. Operative tips and anaesthesia preparation recommendations are given.

A rare case of asymptomatic emphysematous pyelonephritis.

Asymptomatic emphysematous pyelonephritis is a rare but potentially life-threatening disease. Diabetes mellitus is the most recognised risk factor. Aim of this case report is to review evidence of emphysematous pyelonephritis to identify risk factors and treatment options.

Audit of minimally-invasive surgery for submandibular sialolithiasis.

Sialolithiasis is one of most common diseases to affect major salivary glands, with a symptomatic incidence of 27 cases per million per annum. The majority form within the submandibular gland where minimally-invasive treatments have all but eliminated adenectomy. All records of patients presenting with submandibular stones between 1997 and 2015 were reviewed. Stones <5mm were retrieved through endoscopic or radiographic techniques, 5-7mm stones were initially considered for extra-corporeal shock wave lithotripsy, but after poor results were treated through intraoral surgical removal with those >7mm. Follow up was performed at 1 week and 3 months with current status performed with postal and telephone questionnaires. 378 patients had 424 stones removed, successful retrieval in 94% (n=356), with 50 having had previous failures. Median number of stones per patient was 1 (range 1-4), with a mean size of 8.6mm (SD 4.5mm) mainly located at the hilum (50.5%), anterior duct (30%) and Genu (17%). 256 patients (65%) treated through intraoral surgical extraction, 92 (24%) endoscopic alone. Inpatient stay was 1.4 days in first third and 0.5 days in final third. Adenectomy occurred in 14 patients, due to failure to retrieve the sialolith or unresolved symptoms. Complications involved 11 patients with permanent paraesthesia, 7 ranulas and 14 strictures. Patients with preoperative strictures were more likely to develop complications (p=0.002) with paraesthesia being most common. Intraoral minimally-invasive surgery is aesthetic, curative and spares the risk to marginal mandibular nerve and submandibular gland. Length of inpatient stay improved and ranula risk reduced throughout the study.

Staff preparedness for providing palliative and end-of-life care in long-term care homes: Instrument development and validation.

AIM: Although much attention has been on integrating the palliative care approach into services of long-term care homes for older people living with frailty and progressive diseases, little is known about the staff preparedness for these new initiatives. The present study aimed to develop and test the psychometric properties of an instrument for measuring care home staff preparedness in providing palliative and end-of-life care. METHODS: A 16-item instrument, covering perceived knowledge, skill and psychological readiness, was developed. A total of 247 staff members of different ranks from four care homes participated in the study. Exploratory factor analysis using the principal component analysis extraction method with varimax rotation was carried out for initial validation. Known group comparison was carried out to examine its discriminant validity. Reliability of the instrument was assessed based on test-retest reliability of a subsample of 20 participants and the Cronbach's alpha of the items. RESULTS: Exploratory factor analysis showed that the instrument yielded a three-factor solution, which cumulatively accounted for 68.5% of the total variance. Three subscales, namely, willingness, capability and resilience, showed high internal consistency and test-retest reliability. It also showed good discriminant validity between staff members of professional and non-professional groups. CONCLUSIONS: This is a brief, valid and reliable scale for measuring care home staff preparedness for providing palliative and end-of-life care. It can be used to identify their concerns and training needs in providing palliative and end-of-life care, and as an outcome measure to evaluate the effects of interventional studies for capacity building in this regard. Geriatr Gerontol Int 2018; 18: 745-749.

Views of people with schizophrenia and their caregivers towards the needs for psychiatric rehabilitation in urban and rural areas of mainland China.

This qualitative study explores and compares the views of the individuals with schizophrenia and their caregivers in the urban and rural areas of Wuxi towards the needs for psychiatric rehabilitation. The results may more precisely guide the government and policy makers to tailor the corresponding strategies and services. With interview guides, individual face-to-face semi-structured interviews were conducted among a total of 16 participants (four people with schizophrenia and their caregivers in the urban areas and in the rural areas, respectively). All interviews were audio-recorded, transcribed, and analyzed using an inductive approach. The findings revealed commonalities and discrepancies on their views about the needs of rehabilitation interventions and community care, the healthcare resources for medication, the major factors of employment, and the support to caregivers for facilitating recovery. Some policy and service implications to promote psychiatric rehabilitation of the people with schizophrenia and their caregivers in Wuxi are discussed. With careful consideration of the possible socio-cultural differences, the findings may also serve as references for the related researchers and clinicians in other regions in China.