The Pre-Analytical CEN/TS Standard for Microbiome Diagnostics—How Can Research and Development Benefit?

Recently, CEN/TS 17626:2021, the European pre-analytical standard for human specimens intended for microbiome DNA analysis, was published. Although this standard relates to diagnostic procedures for microbiome analysis and is relevant for in vitro diagnostic (IVD) manufacturers and diagnostic laboratories, it also has implications for research and development (R&D). We present here why standards are needed in biomedical research, what pre-analytical standards can accomplish, and which elements of the pre-analytical workflow they cover. The benefits of standardization for the generation of FAIR (findable, accessible, interoperable, reusable) data and to support innovation are briefly discussed.     

Comparison of Melting Processes for WPC and the Resulting Differences in Thermal Damage,Emissions and Mechanics

The necessity for resource-efficient manufacturing technologies requires new developments within the field of plastic processing. Lightweight design using wood fibers as sustainable reinforcement for thermoplastics might be one solution. The processing of wood fibers requires special attention to the applied thermal load. Even at low processing temperatures, the influence of the dwell time, temperature and shear force is critical to ensure the structural integrity of fibers. Therefore, this article compares different compounding rates for polypropylene with wood fibers and highlights their effects on the olfactory, visual and mechanical properties of the injection-molded part. The study compares one-step processing, using an injection-molding compounder (IMC), with two-step processing, using a twin-scew-extruder (TSE), a heating/cooling mixer (HCM) and an internal mixer (IM) with subsequent injection molding. Although the highest fiber length was achieved by using the IMC, the best mechanical properties were achieved by the HCM and IM. The measured oxidation induction time and volatile organic compound content indicate that the lowest amount of thermal damage occurred when using the HCM and IM. The advantage of one-time melting was evened out by the dwell time. The reinforcement of thermoplastics by wood fibers depends more strongly on the structural integrity of the fibers compared to their length and homogeneity.     

Aerobic exercise elicits clinical adaptations in myotonic dystrophy type 1 patients independently of pathophysiological changes

BackgroundMyotonic dystrophy type 1 (DM1) is a complex life-limiting neuromuscular disorder characterized by severe skeletal muscle atrophy, weakness, and cardiorespiratory defects. Exercised DM1 mice exhibit numerous physiological benefits that are underpinned by reduced CUG foci and improved alternative splicing. However, the efficacy of physical activity in patients is unknown.MethodsEleven genetically diagnosed DM1 patients were recruited to examine the extent to which 12 weeks of cycling can recuperate clinical and physiological metrics. Furthermore, we studied the underlying molecular mechanisms through which exercise elicits benefits in skeletal muscle of DM1 patients.RESULTSDM1 was associated with impaired muscle function, fitness, and lung capacity. Cycling evoked several clinical, physical, and metabolic advantages in DM1 patients. We highlight that exercise-induced molecular and cellular alterations in patients do not conform with previously published data in murine models and propose a significant role of mitochondrial function in DM1 pathology. Finally, we discovered a subset of small nucleolar RNAs (snoRNAs) that correlated to indicators of disease severity.ConclusionWith no available cures, our data support the efficacy of exercise as a primary intervention to partially mitigate the clinical progression of DM1. Additionally, we provide evidence for the involvement of snoRNAs and other noncoding RNAs in DM1 pathophysiology.Trial registrationThis trial was approved by the HiREB committee (no. 7901) and registered under ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT04187482","term_id":"NCT04187482"}}NCT04187482).FundingNeil and Leanne Petroff. Canadian Institutes of Health Research Foundation (no. 143325).     

Diagnosing pancreatic cancer in general practice: a cross-sectional study on associations between suspicion of cancer,urgent referral and time to diagnosis

ObjectiveThis study aimed to investigate the first point of contact in patients diagnosed with pancreatic cancer, and to study factors associated with the GP’s suspicion of cancer, Cancer Patient Pathway (CPP) referral and long diagnostic interval.DesignCross-sectional study combining register and survey data.PatientsPatients with incident pancreatic cancer recorded in the Danish National Patient Register (n = 303).Main outcome measuresThe patient’s first point of symptoms presentation, GP’s cancer suspicion, CPP referral and diagnostic interval.ResultsGeneral practice was the first point of contact for 85.5% of the population. At the first consultation, cancer was suspected in 32.7% and 22.9% were referred to a CPP. The GPs were more likely to suspect cancer or serious illness in patients aged >70 years (prevalence rate ratio (PRR) 1.34, 95% CI 1.09–1.66) and among patients with high comorbidity (PRR 1.23, 95% CI 1.04–1.47). A CPP referral was less likely among patients with low education. The median diagnostic interval was 39 days (interquartile range: 15–72). When the GP initially did not suspect cancer, the likelihood of longer diagnostic interval increased.ConclusionThe majority of patients with pancreatic cancer began their diagnostic route in general practice. Diagnosing pancreatic cancer swiftly in general practice was challenging; the GP did often not initially suspect cancer or refer to a CPP and several of the patient characteristics were associated with the GPs initial suspicion of cancer or CPP referral. Thus, there may be room for improvements in the diagnostics of pancreatic cancer in general practice.

Key points

• Patients with pancreatic cancer have a poor prognosis, as pancreatic cancer is often diagnosed in late stage.
• The majority of patients with pancreatic cancer began their diagnostic process in general practice.
• General practitioners (GPs) suspected cancer at the first consultation in one out of three patients with pancreatic cancer; more often in older and comorbid patients.
• The GPs suspicion of cancer was associated with urgent referral and shorter time to diagnosis.

     

Healthcare practices that increase the quality of care in cancer trajectories from a general practice perspective: a scoping review

ObjectiveGeneral practice plays an important role in cancer trajectories, and cancer patients request the continuous involvement of general practice. The objective of this scoping review was to identify healthcare practices that increase the quality of care in cancer trajectories from a general practice perspective.Design, setting, and subjectsA scoping review of the literature published in Danish or English from 2010 to 2020 was conducted. Data was collected using identified keywords and indexed terms in several databases (PubMed, MEDLINE, EBSCO CINAHL, Scopus, and ProQuest), contacting key experts, searching through reference lists, and reports from selected health political, research- and interest organizations’ websites.Main outcome measuresWe identified healthcare practices in cancer trajectories that increase quality care. Identified healthcare practices were grouped into four contextual domains and allocated to defined phases in the cancer trajectory. The results are presented according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for scoping reviews (PRISMA-ScR).ResultsA total of 45 peer-reviewed and six non-peer-reviewed articles and reports were included. Quality of care increases in all phases of the cancer trajectory when GPs listen carefully to the full story and use action plans. After diagnosis, quality of care increases when GPs and practice staff have a proactive care approach, act as interpreters of diagnosis, treatment options, and its consequences, and engage in care coordination with specialists in secondary care involving the patient.ConclusionThis scoping review identified healthcare practices that increase the quality of care in cancer trajectories from a general practice perspective. The results support general practice in investigating own healthcare practices and identifying possibilities for quality improvement.

KEY POINTS

• Identified healthcare practices in general practice that increase the quality of care in cancer trajectories:
• Listen carefully to the full story
• Use action plans and time-out-consultations
• Plan and provide proactive care
• Act as an interpreter of diagnosis, treatment options, and its consequences for the patient
• Coordinate care with specialists, patients, and caregivers with mutual respect
• Identified barriers for quality of care in cancer trajectories are:
• Time constraints in consultations
• Limited accessibility for patients and caregivers
• Health practices to increase the quality of care should be effective, safe, people-centered, timely, equitable, integrated, and efficient. These distinctions of quality of care, support general practice in investigating and improving quality of care in cancer trajectories.

     

Donation after cardiac death liver transplantation is associated with increased risk of end‐stage renal disease

Limited organ supply has led to greater use of liver allografts with higher donor risk indices (DRI) and/or donated after cardiac death (DCD). DCD status is associated with acute kidney injury after liver transplantation; however, less is known about the association between donor quality and end‐stage renal disease (ESRD). Using SRTR data, we assembled a cohort of liver transplant recipients from 2/2002 to 12/2010. We fit multivariable Cox regression models for ESRD. Model 1 included total DRI; model 2 included components of DRI, including DCD, as separate variables. Forty thousand four hundred and sixty‐three liver transplant recipients were included. Median DRI was 1.40 (IQR 1.14, 1.72); 1822 (5%) received DCD livers. During median follow‐up of 3.93 years, ESRD occurred in 2008 (5%) and death in 11 075 (27%) subjects. There was a stepwise increase in ESRD risk with higher DRI (DRI ≥1.14 and <1.40: HR 1.17, P = 0.06; DRI ≥1.40 and <1.72: HR 1.29, P = 0.003; DRI ≥1.72: HR 1.39, P < 0.001, compared with DRI <1.14). Adjusting for DRI components separately, DCD status was most strongly associated with ESRD (HR 1.40, P = 0.008). Higher DRI is associated with ESRD after liver transplantation, driven in part by DCD status. Donor quality is an important predictor of long‐term renal outcomes in liver transplant recipients.     

A Randomized Trial to Assess the Impact of Direct Reporting of DXA Scan Results to Patients on Quality of Osteoporosis Care

Consecutive patients identified as having osteoporosis on screening dual-energy X-ray absorptiometry (DXA) scans were randomized to: (1) a patient activation intervention consisting of mailing patients their DXA scan results supplemented by a call from a nurse educator or (2) usual care. Three months after the DXA scan, patients were contacted to assess: (1) use of antiresorptive therapy, (2) osteoporosis specific knowledge, and (3) satisfaction with their osteoporosis-related care. A total of 1,035 consecutive patients were screened to identify 422 eligible patients. Of these, 56 patients met inclusion criteria and were subsequently randomized. At follow-up, use of antiresorptive agents was numerically more common in the intervention arm (62%) than the control arm (54%), but this difference was not statistically significant (p = 0.58). Patients in the intervention group were more likely to report being notified of their DXA results in a timely fashion (p = 0.03), but osteoporosis-specific knowledge was similar.     

Venous Thromboembolism in Cancer Patients Undergoing Major Surgery

Background  Cancer patients undergoing major abdominal or pelvic surgery are at considerable risk of venous thromboembolism (VTE). The genesis of thromboses in malignancy is complicated, and reflects the interaction and derangement of multiple molecular pathways. Furthermore, the nature and location of the cancer, as well as the type surgery involved, are thought to affect the level of VTE risk. These considerations may therefore affect treatment decisions. Methods  We performed multiple Medline searches with terms including but not limited to VTE, cancer, surgery, abdominal, colorectal, unfractionated heparin (UFH), and low-molecular-weight heparin (LMWH) to identify reviews, meta-analyses, nonrandomized and randomized controlled trials, and clinical guidelines relating to management of VTE in patients with abdominal cancer. Results  VTE incidence in patients with malignancy varied according to cancer type, location, stage of progression, and the use of catheters and/or chemotherapy. Thromboprophylaxis with UFH or LMWH reduces the risk of developing VTE in these patients. However, LMWHs have a favorable risk-benefit profile over UFH and extending the duration prophylaxis may improve outcomes. Conclusion  A number of recommendations can be made for the prevention of VTE in patients undergoing abdominal or pelvic surgery for cancer: (1) risk-stratify all patients according to defined evidence-based guidelines; (2) for most abdominal surgical oncology patients at risk, use of both an anticoagulant and mechanical means are indicated and beneficial; and (3) consider extended-duration prophylaxis (up to 28 days) in those patients with major abdominal/pelvic operations and impaired mobility, preferably with LMWH.     

Hirschsprung-associated enterocolitis develops independently of NOD2 variants

Backgroud/Purpose

Hirschsprung-associated enterocolitis (HAEC) represents a cause for significant pre- and postoperative morbidity and mortality in Hirschsprung disease (HD). Although multiple studies on HAEC have been performed and several mechanisms have been presumed, the pathogenesis of this condition remains unclear. As changes in colonic mucosal defense are key factors suggested in both Crohn's disease (CD) and HAEC pathogenesis, the aim of the current study was to investigate genetic alterations in the most important susceptibility gene for Crohn's enterocolitis (NOD2) to see whether carriers of polymorphisms within the NOD2 gene are predisposed to the development of HAEC.

Methods

Genotyping for the NOD2 variants in exon 4 (p.Arg702Trp [rs2066844]), exon 8 (p.Gly908Arg [rs2066845]), and exon 11 (p.1007fs [rs2066847]) was performed in 52 white children with HD (41 boys, 11 girls), 152 healthy controls, and 152 children with CD (onset of disease <17 years; mean, 11.8 years). Seventeen patients with HD (32.7%) were carriers of a RET germline mutation, 35 children (67.3%) had short segment disease, and 17 (32.7%) had long segment disease.

Results

Ten children (19.2%) with HD were heterozygous carriers of at least one NOD2 variant vs 17 (11.2%) in the healthy control group and 69 (45.4%) in the CD cohort. Hirschsprung-associated enterocolitis was observed in 7 children (13.5%), with 4 having short segment HD and 3 with long segment HD; but none of them were carriers of NOD2 variants.

Conclusion

Our study shows that NOD2 variants described to be causatively associated with CD do not predispose to the development of HAEC. As data on the molecular basis of HAEC are limited, the distinct mechanisms involved in the pathogenesis of this complication remain unclear.