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Quality of life and symptom assessment in paraesophageal hernias: a systematic literature review of reporting standards.
No full textBACKGROUND
Paraesophageal hernias (PEH) present with a range of symptoms affecting physical and mental health. This systematic review aims to assess the quality of reporting standards for patients with PEH, identify the most frequently used quality of life (QOL) and symptom severity assessment tools in PEH and to ascertain additional symptoms reported by these patients not captured by these tools.
METHODS
A systematic literature review according to PRISMA protocols was carried out following a literature search of MEDLINE, Embase and Cochrane databases for studies published between January 1960 and May 2020. Published abstracts from conference proceedings were included. Data on QOL tools used and reported symptoms were extracted.
RESULTS
This review included 220 studies reporting on 28 353 patients. A total of 46 different QOL and symptom severity tools were used across all studies, and 89 different symptoms were reported. The most frequently utilized QOL tool was the Gastro-Esophageal Reflux Disease-Health related quality of life questionnaire symptom severity instrument (47.7%), 57.2% of studies utilized more than 2 QOL tools and 'dysphagia' was the most frequently reported symptom, in 55.0% of studies. Notably, respiratory and cardiovascular symptoms, although less common than GI symptoms, were reported and included 'dyspnea' reported in 35 studies (15.9%).
CONCLUSIONS
There lacks a QOL assessment tool that captures the range of symptoms associated with PEH. Reporting standards for this cohort must be improved to compare patient outcomes before and after surgery. Further investigations must seek to develop a PEH specific tool, that encompasses the relative importance of symptoms when considering surgical intervention and assessing symptomatic improvement following surgery
Development and Relevance of Hypercapnia in COPD.
No full textBackground
Identification of patients who may become hypercapnic, or develop acidotic hypercapnic respiratory failure (AHRF), is important in chronic obstructive pulmonary disease (COPD) to avoid hospital admission and select patients for use of home NIV. This study aimed to identify factors associated with presence and development of hypercapnia.
Methods
1224 patients, 637 with COPD and 587 with alpha 1 antitrypsin deficiency (AATD), from 4 previously established patient cohorts, were included in cross-sectional analyses of hypercapnia (PaCO ≥ 6.5 kPa or 48.8 mmHg), focusing on phenotypic features of COPD and mortality. Longitudinal associations of rising PaCO were also assessed. A second cohort of 160 COPD patients underwent sleep studies and 1-year follow-up, analysing in a similar way, incorporating additional information from their sleep studies if appropriate.
Results
Hypercapnia was 15 times more common in usual COPD than AATD ( < 0.01) after adjustment for baseline differences by regression. Independent predictors of hypercapnia in COPD included FEV and current use of oxygen; these variables, together with lack of emphysema, explained 11% of variance in CO. Increasing PaCO also associated with higher risk of death (=0.03). 44/160 patients exhibited sleep disordered breathing. The sleep study cohort also showed an association of low FEV with hypercapnia. Prior hospital admission for AHRF was also clinically significant, being a feature of almost double the number of hypercapnic patients in both test and sleep study COPD cohorts.
Conclusion
Lower FEV and prior AHRF are the main associations of hypercapnia in COPD, which carries a poor prognosis, particularly worsening over time
Assessment, endoscopy, and treatment in patients with acute severe ulcerative colitis during the COVID-19 pandemic (PROTECT-ASUC): a multicentre, observational, case-control study.
No full textBACKGROUND
There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes.
METHODS
The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov, NCT04411784.
FINDINGS
We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes.
INTERPRETATION
The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes.
FUNDING
None
Ex vivo modelling of PD-1/PD-L1 immune checkpoint blockade under acute, chronic, and exhaustion-like conditions of T-cell stimulation.
No full textBlockade of PD-1/PD-L1 interactions is proving an exciting, durable therapeutic modality in a range of cancers whereby T cells are released from checkpoint inhibition to revive their inherent anti-tumour activity. Here we have studied various ways to model ex vivo T cell function in order to compare the impact of the clinically utilised anti-PD-1 antibody, pembrolizumab (Keytruda) on the activation of human T cells: focussing on the release of pro-inflammatory IFNγ and anti-inflammatory IL-10 to assess functionality. Firstly, we investigated the actions of pembrolizumab in an acute model of T-cell activation with either immature or mature allogeneic dendritic cells (DCs); pembrolizumab enhanced IFNγ and IL-10 release from purified CD4+ T-cells in the majority of donors with a bias towards pro-inflammatory cytokine release. Next, we modelled the impact of pembrolizumab in settings of more chronic T-cell activation. In a 7-day antigen-specific response to EBV peptides, the presence of pembrolizumab resulted in a relatively modest increase in both IFNγ and IL-10 release. Where pembrolizumab was assessed against long-term stimulated CD4+ cells that had up-regulated the exhaustion markers TIM-3 and PD-1, there was a highly effective enhancement of the otherwise exhausted response to allogeneic DCs with respect to IFNγ production. By contrast, the restoration of IL-10 production was considerably more limited. Finally, to assess a direct clinical relevance we investigated the consequence of PD-1/PD-L1 blockade in the disease setting of dissociated cells from lung and colon carcinomas responding to allogeneic DCs: here, pembrolizumab once more enhanced IFNγ production from the majority of tumour preparations whereas, again, the increase in IL-10 release was modest at best. In conclusion, we have shown that the contribution of PD-1-revealed by using a canonical blocking antibody to interrupt its interaction with PD-L1-to the production of an exemplar pro- and anti-inflammatory cytokine, respectively, depends in magnitude and ratio on the particular stimulation setting and activation status of the target T cell. We have identified a number of in vitro assays with response profiles that mimic features of dissociated cell populations from primary tumours thereby indicating these represent disease-relevant functional assays for the screening of immune checkpoint inhibitors in current and future development. Such in vitro assays may also support patient stratification of those likely to respond to immuno-oncology therapies in the wider population
Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis.
No full textBACKGROUND
Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis.
METHODS
We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284.
FINDINGS
16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m), 530 (23%) were overweight (BMI ≥25 to <30 kg/m), and 1080 (47%) were obese (BMI ≥30 kg/m). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low.
INTERPRETATION
CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard.
FUNDING
The German Federal Ministry of Education and Research and Echosens
The gut microbiome: what every gastroenterologist needs to know.
No full textThe mucosal surfaces of the body are characterised by complex, specialised microbial communities, often referred to as the . However, only much more recently-with the development of technologies allowing exploration of the composition and functionality of these communities-has meaningful research in this area become feasible. Over the past few years, there has been rapid growth in interest in the gut microbiome in particular, and its potential contribution to gastrointestinal and liver disease. This interest has already extended beyond clinicians to pharmaceutical companies, medical regulators and other stakeholders, and is high profile among patients and the lay public in general. Such expansion of knowledge holds the intriguing potential for translation into novel diagnostics and therapeutics; however, being such a nascent field, there remain many uncertainties, unanswered questions and areas of debate
Discovered cancers at postmortem donor examination: A starting point for quality improvement of donor assessment.
No full textBACKGROUND
clinical and imaging investigations allow a detailed assessment of an organ donor, but a quota of cancer still elude detection. Complete autopsy of donors is even less frequently performed, due to economic issues and increasing availability of high-quality imaging. The aim of this study is to gather evidence from the literature on donor malignancy discovered at autopsy following organ donation and to discuss the utility and limitations of autopsy practice in the field of transplantation.
METHODS
A systematic search according to PRISMA guidelines was carried out in Pubmed and Embase databases until September 2020 to select articles with reporting of cancer discovered in a donor at postmortem examination. Cancer discover in not-transplant setting were excluded. A descriptive synthesis was provided.
RESULTS
Of 7388 articles after duplicates removal, 56 were included. Fifty-one studies reported on complete autopsy, while 5 dealt only with limited autopsy (prostate and central nervous system). The number of autopsies ranged between 1 and 246 with a total of 823 autopsies performed. The most frequent cancer discovered at autopsy was lymphoma (n = 13, 15%), followed by renal cell carcinoma (RCC) (n = 11, 13%), non-small cell lung cancer (NSCLC) (n = 10, 11%), melanoma (n = 10, 11%), choriocarcinoma (n = 6, 7%) and glioblastoma (GBM) (n = 6, 7%).
CONCLUSIONS
Lymphoma and melanoma are still difficult-to-detect cancers both during donor investigation and at procurement, whilst prostate cancer and choriocarcinoma are almost always easily detected nowadays thank to blood markers and clinical examination. There have been improvements with time in pre-donation detection procedures which are now working well, particularly when complete imaging investigations are performed, given that detection rate of CT/MRI is high and accurate. Autopsy can play a role to help to establish the correct donor management pathways in case of cancer discover. Furthermore, it helps to better understand which cancers are still eluding detection and consequently to refine guidelines' assessment procedures