Update on Glucose Management Among Noncritically Ill Patients Hospitalized on Medical and Surgical Wards

Hyperglycemia is a common issue affecting inpatient care. Although this is in part because of the higher rate of hospitalization among patients with preexisting diabetes, multiple factors complicate inpatient glucose management, including acute stress from illness or surgery, erratic dietary intake, and contribution of medications. It has been repeatedly demonstrated that poorly controlled blood glucose levels are associated with negative clinical outcomes, such as increased mortality, higher rate of surgical complications, and longer length of hospital stay. Given these concerns, there has been extensive study of the optimal strategy for management of glucose levels, with the bulk of existing literature focusing on insulin therapy in the intensive care unit setting. This review shifts the focus to the general adult medical and surgical wards, using clinical guidelines and sentinel studies to describe the scientific basis behind the current basal-bolus insulin-based approach to blood sugar management among noncritically ill inpatients. Patient-centered clinical trials looking at alternative dosing regimens and insulin analog and noninsulin agents, such as glucagon-like peptide-1 agonist therapies, introduce safe and effective options in the management of inpatient hyperglycemia. Data from these studies reveal that these approaches are of comparable safety and efficacy to the traditional basal-bolus insulin regimen, and may offer additional benefit in terms of less monitoring requirements and lower rates of hypoglycemia. Although existing data are encouraging, outcome studies will be needed to better establish the clinical impact of these more recently proposed approaches in an effort to broaden and improve current clinical practices in inpatient diabetes care

Inflammatory prognostic scoring systems are risk factors for surgical site infection following wide local excision of soft tissue sarcoma

Introduction: Limb-sparing surgery with negative margins is possible in most soft tissue sarcoma (STS) resections and focuses on maximising function and minimising morbidity. Various risk factors for surgical site infections (SSIs) have been reported in the literature specific to sarcoma surgery. The aim of this study is to determine whether systemic inflammatory response prognostic scoring systems can predict post-operative SSI in patients undergoing potentially curative resection of STS. Methods: Patients who had a planned curative resection of a primary STS at a single centre between January 2010 and December 2019 with a minimum follow-up of 6 months were included. Data were extracted on patient and tumour characteristics, and pre-operative blood results were used to calculate inflammatory prognostic scores based on published thresholds and correlated with risk of developing SSI or debridement procedures. Results: A total of 187 cases were included. There were 60 SSIs. On univariate analysis, there was a statistically significant increased risk of SSI in patients who are diabetic, increasing specimen diameter, American Society of Anaesthesiology (ASA) grade 3, use of endoprosthetic replacement, blood loss greater than 1 L, and junctional tumour location. Modified Glasgow prognostic score, C-reactive protein/albumin ratio and neutrophil–platelet score (NPS) were statistically associated with the risk of SSI. On multivariate analysis, ASA grade 3, junctional tumour location and NPS were independently associated with the risk of developing a SSI. Conclusion: This study supports the routine use of simple inflammation-based prognostic scores in identifying patients at increased risk of developing infectious complications in patients undergoing potentially curative resection of STS

Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: a retrospective observational cohort study

BackgroundThe association between objective imaging response and first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in routine practice.MethodsWe conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from August 2013-May 2020 in Alberta, Canada. The primary outcome was likelihood of RECIST v1.1 assessed objective imaging response between patients receiving anti-programmed cell death protein 1 (anti-PD1) monotherapy and those receiving combination ipilimumab-nivolumab. Secondary outcomes were identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT).Results198 patients were included, 41/198 (20.7%) had complete response, 86/198 (43.4%) had partial response, 23/198 (11.6%) had stable disease, and 48/198 (24.2%) had progressive disease. Median OS was not reached (NR) (95% CI 49.0-NR) months for complete responders, NR (95%CI 52.9-NR) months for partial responders, 33.7 (95%CI 15.8-NR) months for stable disease, and 6.4 (95%CI 5.2–10.1) months for progressive disease (log-rank p<0.001). Likelihood of objective imaging response remained similar between anti-PD1 monotherapy and ipilimumab-nivolumab groups (OR 1.95 95%CI 0.85–4.63, p=0.121). Elevated LDH level (OR 0.46; 95%CI 0.21–0.98, p=0.043), mucosal primary site (OR 0.14; 95%CI 0.03–0.48, p=0.003), and BRAF V600E mutation status (OR 0.31; 95%CI 0.13–0.72, p=0.007) were associated with decreased likelihood of response.ConclusionNo significant difference in likelihood of imaging response between anti-PD1 monotherapy and combination ipilimumab-nivolumab was observed. Elevated LDH level, mucosal primary site, and BRAF V600E mutation status were associated with decreased likelihood of response. Given that pivotal clinical trials of ipilimumab-nivolumab did not formally compare ipilimumab-nivolumab with nivolumab monotherapy, this work adds context to differences in outcomes when these agents are used. These results may inform treatment selection, and aid in counseling of patients treated with first-line ICI therapy in routine clinical practice settings

Subtelomeric CTCF and cohesin binding site organization using improved subtelomere assemblies and a novel annotation pipeline

Mapping genome-wide data to human subtelomeres has been problematic due to the incomplete assembly and challenges of low-copy repetitive DNA elements. Here, we provide updated human subtelomere sequence assemblies that were extended by filling telomere-adjacent gaps using clone-based resources. A bioinformatic pipeline incorporating multiread mapping for annotation of the updated assemblies using short-read data sets was developed and implemented. Annotation of subtelomeric sequence features as well as mapping of CTCF and cohesin binding sites using ChIP-seq data sets from multiple human cell types confirmed that CTCF and cohesin bind within 3 kb of the start of terminal repeat tracts at many, but not all, subtelomeres. CTCF and cohesin co-occupancy were also enriched near internal telomere-like sequence (ITS) islands and the nonterminal boundaries of subtelomere repeat elements (SREs) in transformed lymphoblastoid cell lines (LCLs) and human embryonic stem cell (ES) lines, but were not significantly enriched in the primary fibroblast IMR90 cell line. Subtelomeric CTCF and cohesin sites predicted by ChIP-seq using our bioinformatics pipeline (but not predicted when only uniquely mapping reads were considered) were consistently validated by ChIP-qPCR. The colocalized CTCF and cohesin sites in SRE regions are candidates for mediating long-range chromatin interactions in the transcript-rich SRE region. A public browser for the integrated display of short-read sequence–based annotations relative to key subtelomere features such as the start of each terminal repeat tract, SRE identity and organization, and subtelomeric gene models was established

The phase structure of the Polyakov--quark-meson model beyond mean field

The Polyakov-extended quark-meson model (PQM) is investigated beyond mean-field. This represents an important step towards a fully dynamical QCD computation. Both the quantum fluctuations to the matter sector and the back-reaction of the matter fluctuations to the QCD Yang-Mills sector are included. Results on the chiral and confinement-deconfinement crossover/phase transition lines and the location of a possible critical endpoint are presented. Moreover, thermodynamic quantities such as the pressure and the quark density are discussed.Comment: 12 pages, 11 figure

An unusual cause of alveolar hemorrhage post hematopoietic stem cell transplantation: A case report

BACKGROUND: Hematopoietic stem cell transplantation is being increasingly used in cancer therapy. Diffuse alveolar hemorrhage, an early complication of stem cell transplant, results from bacterial, viral and fungal infections, coagulopathy, and engraftment syndrome, or can be idiopathic. Diffuse alveolar hemorrhage associated with Strongyloides stercoralis hyperinfection in stem cell transplant patients has been rarely reported. CASE PRESENTATION: We describe an unusual cause of alveolar hemorrhage post hematopoietic stem cell transplant due to Strongyloides hyperinfection. Therapy with parenteral ivermectin and thiabendazole was initiated but the patient deteriorated and died of respiratory failure and septic shock. CONCLUSION: Strongyloides stercoralis hyperinfection is an unusual cause of alveolar hemorrhage early after hematopoietic stem cell transplant with very high mortality

School policies, built environment and practices for non-communicable disease (NCD) prevention and control in schools of Delhi, India.

OBJECTIVE: To assess school policies, built environment and practices for prevention and control of non-communicable diseases in schools of Delhi, India. METHODS: School built environments and policies were assessed using a structured observation checklist in 10 private and 9 government schools which were randomly selected from all 184 co-educational schools with primary to senior secondary level education in Delhi, India. A self-administered questionnaire was also completed by teachers from each school (n = 19) to capture information specific to school policies. Surveys were also conducted with parent of students in class II (aged 6-7 years; n = 574) and student in class XI (aged 15-16 years, n = 755) to understand school practices. RESULTS: The majority of government (88.9%; n = 8) and private (80%; n = 8) schools reported having comprehensive school health policy. In terms of specific health behaviours, policies related to diet and nutrition in government schools were mostly restricted to primary levels with provision of the mid-day meal programme. All schools had two physical education periods per week of about 45-50 minutes. Most schools were compliant with tobacco-free school guidelines (n = 15 out of 19) and had alcohol control policies (n = 13 out of 19). Parent and student reports of practices indicated that school policies were not consistently implemented. CONCLUSION: Most schools in Delhi have policies that address health behaviours in students, but there was considerable variation in the types and number of policies and school environments. Government schools are more likely to have policies in place than private schools. Further work is needed to evaluate how these policies are implemented and to assess their impact on health outcomes

Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat

International audienceBACKGROUND: More than half of pregnant women in the Western world report intake of mild analgesics, and some of these drugs have been associated with anti-androgenic effects in animal experiments. Intrauterine exposure to anti-androgens is suspected to contribute to the recent increase in male reproductive problems, and many of the anti-androgenic compounds are like the mild analgesics potent inhibitors of prostaglandin synthesis. Therefore, it appears imperative to further investigate the potential endocrine disrupting properties of mild analgesics. METHODS: In a prospective birth cohort study, 2297 Danish and Finnish pregnant women completed a questionnaire and 491 of the Danish mothers participated in a telephone interview, reporting on their use of mild analgesics during pregnancy. The testicular position of newborns was assessed by trained paediatricians. In rats, the impact of mild analgesics on anogenital distance (AGD) after intrauterine exposure was examined together with the effect on ex vivo gestational day 14.5 testes. RESULTS: In the Danish birth cohort, the use of mild analgesics was dose-dependently associated with congenital cryptorchidism. In particular, use during the second trimester increased the risk. This risk was further increased after the simultaneous use of different analgesics. The association was not found in the Finnish birth cohort. Intrauterine exposure of rats to paracetamol led to a reduction in the AGD and mild analgesics accordingly reduced testosterone production in ex vivo fetal rat testes. CONCLUSION: There was an association between the timing and the duration of mild analgesic use during pregnancy and the risk of cryptorchidism. These findings were supported by anti-androgenic effects in rat models leading to impaired masculinization. Our results suggest that intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders

How does climate exacerbate root causes of conflict in Mali?

This factsheet gives answers on how climate exacerbates root causes of conflict in Mali, using an impact pathway analysis. Two main impact pathways are identified: 1. Livelihood and Food Security: Climate variability and extreme weather events undermine the viability of climate-sensitive livelihoods dependent on natural resources such as livestock, agriculture, and fishery. While seasonal migration has been a frequent adaptation strategy, migration patterns are becoming more permanent, leading to increased competition in host communities. At the same time, livelihood insecurity has been a driver for recruitment into non-state armed groups, exacerbating conflict dynamics.; 2. Resource Availability and Access: Climate change and variability impact resource availability and environmental conditions, contributing to an increase in the competition over the access and use of natural resources, reducing levels of social cohesion, and increasing conflicts between and among different livelihood groups. Disputes for access and use of limited resource availability concerns mostly land and water sources, crucial for Mali’s agricultural sector