Assessment of nutritional status and nutrition impact symptoms in patients undergoing resection for upper gastrointestinal cancer: Results from the multi-centre nourish point prevalence study

Background: Identification and treatment of malnutrition are essential in upper gastrointestinal (UGI) cancer. However, there is limited understanding of the nutritional status of UGI cancer patients at the time of curative surgery. This prospective point prevalence study involving 27 Australian tertiary hospitals investigated nutritional status at the time of curative UGI cancer resection, as well as presence of preoperative nutrition impact symptoms, and associations with length of stay (LOS) and surgical complications. Methods: Subjective global assessment, hand grip strength (HGS) and weight were performed within 7 days of admission. Data on preoperative weight changes, nutrition impact symptoms, and dietary intake were collected using a purpose-built data collection tool. Surgical LOS and complications were also recorded. Multivariate regression models were developed for nutritional status, unintentional weight loss, LOS and complications. Results: This study included 200 patients undergoing oesophageal, gastric and pancreatic surgery. Malnutrition prevalence was 42% (95% confidence interval (CI) 35%, 49%), 49% lost ≥5% weight in 6 months, and 47% of those who completed HGS assessment had low muscle strength with no differences between surgical procedures (p = 0.864, p = 0.943, p = 0.075, respectively). The overall prevalence of reporting at least one preoperative nutrition impact symptom was 55%, with poor appetite (37%) and early satiety (23%) the most frequently reported. Age (odds ratio (OR) 4.1, 95% CI 1.5, 11.5, p = 0.008), unintentional weight loss of ≥5% in 6 months (OR 28.7, 95% CI 10.5, 78.6, p < 0.001), vomiting (OR 17.1, 95% CI 1.4, 207.8, 0.025), reduced food intake lasting 2–4 weeks (OR 7.4, 95% CI 1.3, 43.5, p = 0.026) and ≥1 month (OR 7.7, 95% CI 2.7, 22.0, p < 0.001) were independently associated with preoperative malnutrition. Factors independently associated with unintentional weight loss were poor appetite (OR 3.7, 95% CI 1.6, 8.4, p = 0.002) and degree of solid food reduction of <75% (OR 3.3, 95% CI 1.2, 9.2, p = 0.02) and <50% (OR 4.9, 95% CI 1.5, 15.6, p = 0.008) of usual intake. Malnutrition (regression coefficient 3.6, 95% CI 0.1, 7.2, p = 0.048) and unintentional weight loss (regression coefficient 4.1, 95% CI 0.5, 7.6, p = 0.026) were independently associated with LOS, but no associations were found for complications. Conclusions: Despite increasing recognition of the importance of preoperative nutritional intervention, a high proportion of patients present with malnutrition or clinically significant weight loss, which are associated with increased LOS. Factors associated with malnutrition and weight loss should be incorporated into routine preoperative screening. Further investigation is required of current practice for dietetics interventions received prior to UGI surgery and if this mitigates the impact on clinical outcomes

Preoperative nutrition intervention in patients undergoing resection for upper gastrointestinal cancer: Results from the multi-centre nourish point prevalence study:Results from the Multi-Centre NOURISH Point Prevalence Study

Background: Preoperative nutrition intervention is recommended prior to upper gastrointestinal (UGI) cancer resection; however, there is limited understanding of interventions received in current clinical practice. This study investigated type and frequency of preoperative dietetics intervention and nutrition support received and clinical and demographic factors associated with receipt of intervention. Associations between intervention and preoperative weight loss, surgical length of stay (LOS), and complications were also investigated. Methods: The NOURISH Point Prevalence Study was conducted between September 2019 and May 2020 across 27 Australian tertiary centres. Subjective global assessment and weight were performed within 7 days of admission. Patients reported on preoperative dietetics and nutrition intervention, and surgical LOS and complications were recorded. Results: Two-hundred patients participated (59% male, mean (standard deviation) age 67 (10)). Sixty percent had seen a dietitian preoperatively, whilst 50% were receiving nutrition support (92% oral nutrition support (ONS)). Patients undergoing pancreatic surgery were less likely to receive dietetics intervention and nutrition support than oesophageal or gastric surgeries (p 2 weeks had lower mean (SD) percentage weight loss than those who did not (1.2 (1.8) vs. 2.9 (3.4), p = 0.001). In malnourished patients, total dietetics appointments ≥3 was independently associated with reduced surgical complications (odds ratio 0.2, 95% confidence interval (CI) 0.1, 0.9, p = 0.04), and ONS >2 weeks was associated with reduced LOS (regression coefficient −7.3, 95% CI −14.3, −0.3, p = 0.04). Conclusions: Despite recommendations, there are low rates of preoperative dietetics consultation and nutrition support in this population, which are associated with increased preoperative weight loss and risk of increased LOS and complications in malnourished patients. The results of this study provide insights into evidence–practice gaps for improvement and data to support further research regarding optimal methods of preoperative nutrition support

A service evaluation and stakeholder perspectives of an innovative digital minor illness referral service from NHS 111 to community pharmacy.

The management of minor conditions represents a significant burden for urgent and emergency care services and reduces the capacity to provide specialist care for higher acuity healthcare need. A pilot Digital Minor Illness Service (DMIRS) was commenced in the North East of England in December 2017 to feasibility test the NHS 111 referral to community pharmacy for patients presenting with minor conditions. A formative evaluation of the service activity data and qualitative investigation of stakeholders involved in the service design, management, delivery and use, aims to present and investigate the service outcomes. Routine service activity data was evaluated during Jan-Dec 2018 to investigate the demographics of patients included in the service; the presenting conditions; and how those referrals were managed by community pharmacies. Semi-structured interviews with NHS 111 call handlers, project team members, community pharmacists and patients were undertaken to investigate the design, management, implementation and delivery of the service. 13,246 NHS 111 patient calls were referred to community pharmacy during the evaluative period. The most common presenting conditions were acute pain (n = 1144, 8.6%) and cough (n = 887, 6.7%). A large volume of complaints (47.1%, 6233) were resolved in community pharmacy. Stakeholders explained the structured approach to service design, organisation and implementation facilitated successful delivery and management. Patients reported positive experiences with accessing care via DMIRS. DMIRS demonstrated that patients could be referred to community pharmacy for the management of minor conditions, shifting a burden away from urgent and emergency care. The service data provides key information for further optimisation of service design, and stakeholder training and awareness. The service was acceptable and valued by patients. Evidence from the DMIRS pilot has been utilised to inform recent national healthcare policy and practice around the management of minor conditions within the urgent and emergency care setting.HN received funds to undertake evaluative work for the Digital Minor Illness Referral Service from NHS England (Grant number: BH181784). The funder provided support in the form of salaries for authors [HN], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ sectio

Identifying Knowledge Gaps with Administrative Health Data: A Cohort Study of Traumatic and Non-Traumatic Spinal Cord Injury in Alberta

Introduction The Spinal Cord Injury (SCI) population consists of two main sub-groups: traumatic (TSCI) and non-traumatic (NTSCI). TSCI has been studied; however less attention has been given to NTSCI. It is important to understand both SCI sub-groups for identification of knowledge gaps and subsequent health service planning. Objectives and Approach The goal is to study the SCI population (both TSCI and NTSCI) in Alberta, Canada, leveraging recent administrative health data. It is difficult to identify NTSCI patients for their heterogeneous conditions, and relatively low prevalence. Consequently, we followed a validated algorithm using particular ICD-10-CA codes, to identify (and index) adult SCI patients from Ambulatory and Inpatient records between April 1, 2006 and March 31, 2016. Indexed patients were linked to various databases (inpatient, ambulatory, physician claims, provincial insurance registry), and analyzed in multiple perspectives such as demographics patterns, deaths, resource and cost utilization, geographic distribution, and care equity between groups. Results Through 10 years of data we have identified 5217 SCI patients (3309 TSCI; 1908 NTSCI). 68.7% TSCI and 58.6% NTSCI are male. NTSCI patients are approximately 10 years older (46.3 TSCI; 54.5 NTSCI), and have a 3-point higher Charlson score. 1-year mortality in NTSCI is approximately 2.4 times the TSCI group. Hospitalizations, ER visits, critical care time have also been examined. Patients with NTSCI had a higher median index LOS (14 days IQR (4-51)) compared to the traumatic group who had much higher variability (11 days IQR (11-65.5)). Noted 13.7% NTSCI patients and 19.5% TSCI do not have hospitalizations after index (a diverse characteristic of SCI). Resource Intensity Weights, physician billing, rural-urban area utilization have also been compared between the sub-groups. Conclusion/Implications With the use of administrative databases and a validated algorithm, we described a diverse patient cohort with two main sub-groups (TSCI/NTSCI). Both groups were analyzed upon multiple topics and showed variations. Our results have provided updated knowledge of a comprehensive SCI population in Alberta, Canada, and may lead to improvements on care-giving model

Use of plasma DNA to predict mortality and need for intensive care in patients with abdominal pain

Background We investigated the value of plasma deoxyribonucleic acid concentrations in patients presenting with acute abdominal pain to predict need for intensive care or mortality. Methods Plasma deoxyribonucleic acid taken from patients with acute abdominal pain was analyzed for the β-globin gene using the quantitative polymerase chain reaction. The primary outcome measure was the combined 28-day mortality or admission to the intensive care unit. Results Of 287 consecutive patients with acute abdominal pain recruited, 12 patients were admitted to the intensive care unit and/or died. Median plasma DNA concentrations were higher in patients with cancer and major organ inflammation. Mean plasma DNA concentrations were three-fold higher in patients with systemic inflammatory response syndrome, five-fold higher in patients who died within 28 days, and eight-fold higher in patients admitted to the intensive care unit. The area under the receiver operator curve for plasma DNA concentrations and intensive care unit admission/mortality was 0.804. At a cut-off of 1100 GE/ml, the sensitivity was 67% (95%CI 35–90) and specificity was 89% (95%CI 84–92). At a cut-off of 175 GE/ml, the sensitivity was 100% (95%CI 73–100) and specificity was 30% (95%CI 25–36). Plasma DNA concentration predicted need for intensive care unit admission or death (adjusted odds ratio 1.4; P < 0.0001). Conclusions Plasma DNA may have a role in patients with acute abdominal pain as a marker for inflammation and cancer, and a predictor of intensive care unit admission/mortality

Associations between the 17q21 region and allergic rhinitis in 5 birth cohorts

Non peer reviewe

Sodium-Glucose Cotransporter 2 Inhibitors and the Risk of Pneumonia and Septic Shock

CONTEXT: Individuals with type 2 diabetes mellitus (DM) have an increased risk of pneumonia and septic shock. Traditional glucose-lowering drugs have recently been found to be associated with a higher risk of infections. It remains unclear whether sodium-glucose cotransporter 2 inhibitors (SGLT2is), which have pleiotropic/anti-inflammatory effects, may reduce the risk of pneumonia and septic shock in DM. METHODS: MEDLINE, Embase, and ClinicalTrials.gov were searched from inception up to May 19, 2022, for randomized, placebo-controlled trials of SGLT2i that included patients with DM and reported outcomes of interest (pneumonia and/or septic shock). Study selection, data extraction, and quality assessment (using the Cochrane Risk of Bias Assessment Tool) were conducted by independent authors. A fixed-effects model was used to pool the relative risk (RRs) and 95% CI across trials. RESULTS: Out of 4568 citations, 26 trials with a total of 59 264 patients (1.9% developed pneumonia and 0.2% developed septic shock) were included. Compared with placebo, SGLT2is significantly reduced the risk of pneumonia (pooled RR 0.87, 95% CI 0.78-0.98) and septic shock (pooled RR 0.65, 95% CI 0.44-0.95). There was no significant heterogeneity of effect size among trials. Subgroup analyses according to the type of SGLT2i used, baseline comorbidities, glycemic control, duration of DM, and trial follow-up showed consistent results without evidence of significant treatment-by-subgroup heterogeneity (all P(heterogeneity) > .10). CONCLUSION: Among DM patients, SGLT2is reduced the risk of pneumonia and septic shock compared with placebo. Our findings should be viewed as hypothesis generating, with concepts requiring validation in future studies

Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure

Introduction: Although checkpoint inhibitors (CPIs) have improved outcomes for patients with metastatic melanoma, those progressing on CPIs have limited therapeutic options. To address this unmet need and overcome CPI resistance mechanisms, novel immunotherapies, such as T-cell engaging agents, are being developed. The use of these agents has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs), which is challenging to predict preclinically and can lead to neutralization of the drug and loss of efficacy. Methods: TYRP1-TCB (RO7293583; RG6232) is a T-cell engaging bispecific (TCB) antibody that targets tyrosinase-related protein 1 (TYRP1), which is expressed in many melanomas, thereby directing T cells to kill TYRP1-expressing tumor cells. Preclinical studies show TYRP1-TCB to have potent anti-tumor activity. This first-in-human (FIH) phase 1 dose-escalation study characterized the safety, tolerability, maximum tolerated dose/optimal biological dose, and pharmacokinetics (PK) of TYRP1-TCB in patients with metastatic melanoma (NCT04551352). Results: Twenty participants with cutaneous, uveal, or mucosal TYRP1-positive melanoma received TYRP1-TCB in escalating doses (0.045 to 0.4 mg). All participants experienced ≥1 treatment-related adverse event (TRAE); two participants experienced grade 3 TRAEs. The most common toxicities were grade 1–2 cytokine release syndrome (CRS) and rash. Fractionated dosing mitigated CRS and was associated with lower levels of interleukin-6 and tumor necrosis factor-alpha. Measurement of active drug (dual TYPR1- and CD3-binding) PK rapidly identified loss of active drug exposure in all participants treated with 0.4 mg in a flat dosing schedule for ≥3 cycles. Loss of exposure was associated with development of ADAs towards both the TYRP1 and CD3 domains. A total drug PK assay, measuring free and ADA-bound forms, demonstrated that TYRP1-TCB-ADA immune complexes were present in participant samples, but showed no drug activity in vitro. Discussion: This study provides important insights into how the use of active drug PK assays, coupled with mechanistic follow-up, can inform and enable ongoing benefit/risk assessment for individuals participating in FIH dose-escalation trials. Translational studies that lead to a better understanding of the underlying biology of cognate T- and B-cell interactions, ultimately resulting in ADA development to novel biotherapeutics, are needed

High-resolution mapping reveals topologically distinct cellular pools of phosphatidylserine

Phosphatidylserine exists lumenally in the ER, Golgi, and mitochondria but cytoplasmically in the trans-Golgi and at the plasma membrane, which suggests that functionally important flipping may occur during trafficking