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Corrigendum: Automated detection of bacterial growth on 96-well plates for high-throughput drug susceptibility testing of .
No full textVascular calcification does not predict anastomotic leak or conduit necrosis following oesophagectomy.
No full textBACKGROUND
Anastomotic leaks (AL) and gastric conduit necrosis (CN) are serious complications following oesophagectomy. Some studies have suggested that vascular calcification may be associated with an increased AL rate, but this has not been validated in a United Kingdom population.
AIM
To investigate whether vascular calcification identified on the pre-operative computed tomography (CT) scan is predictive of AL or CN.
METHODS
Routine pre-operative CT scans of 414 patients who underwent oesophagectomy for malignancy with oesophagogastric anastomosis at the Queen Elizabeth Hospital Birmingham between 2006 and 2018 were retrospectively analysed. Calcification of the proximal aorta, distal aorta, coeliac trunk and branches of the coeliac trunk was scored by two reviewers. The relationship between these calcification scores and occurrence of AL and CN was then analysed. The Esophagectomy Complications Consensus Group definition of AL and CN was used.
RESULTS
Complication data were available in 411 patients, of whom 16.7% developed either AL (15.8%) or CN (3.4%). Rates of AL were significantly higher in female patients, at 23.0%, compared to 13.9% in males ( 0.047). CN was significantly more common in females, (8.0% 2.2%, 0.014), patients with diabetes (10.6% 2.5%, 0.014), a history of smoking (10.3% 2.3%, 0.008), and a higher American Society of Anaesthesiologists grade ( 0.024). Out of the 14 conduit necroses, only 4 occurred without a concomitant AL. No statistically significant association was found between calcification of any of the vessels studied and either of these outcomes. Multivariable analyses were then performed to identify whether a combination of the calcification scores could be identified that would be significantly predictive of any of the outcomes. However, the stepwise approach did not select any factors for inclusion in the final models. The analysis was repeated for composite outcomes of those patients with either AL or CN ( 69, 16.7%) and for those with both AL and CN ( 10, 2.4%) and again, no significant associations were detected. In the subset of patients that developed these outcomes, no significant associations were detected between calcification and the severity of the complication.
CONCLUSION
Calcification scoring was not significantly associated with Anastomotic Leak or CN in our study, therefore should not be used to identify patients who are high risk for these complications
High cutoff versus high-flux haemodialysis for myeloma cast nephropathy in patients receiving bortezomib-based chemotherapy (EuLITE): a phase 2 randomised controlled trial.
No full textBACKGROUND
In multiple myeloma, severe acute kidney injury due to myeloma cast nephropathy is caused by pathogenic free light chain immunoglobulin in serum. High cutoff haemodialysis (HCO-HD) can remove large quantities of free light chain immunoglobulin from serum, but its effect on clinical outcomes is uncertain. We therefore aimed to assess whether HCO-HD could increase the frequency of renal recovery in patients with de novo multiple myeloma, severe acute kidney injury, and myeloma cast nephropathy relative to treatment with standard high-flux haemodialysis (HF-HD).
METHODS
In this open-label, phase 2, multicentre, randomised controlled trial (EuLITE), we recruited patients with newly diagnosed multiple myeloma, biopsy-confirmed cast nephropathy, and acute kidney injury that required dialysis from renal services in 16 hospitals in the UK and Germany. Patients were randomly assigned (1:1) by random number generation to receive intensive HCO-HD (in sessions lasting 6-8 h) or standard HF-HD and they were stratified by age and centre. Patients and the medical staff treating them were not masked to treatment allocation. Patients received bortezomib, doxorubicin, and dexamethasone chemotherapy, and were then followed up for 2 years. The primary outcome was independence from dialysis at 90 days after random allocation to groups, which was assessed in an intention-to-treat population. The trial has completed follow-up, and is registered at the ISRCTN registry, number ISRCTN45967602.
FINDINGS
Between June 7, 2008, and Sept 18, 2013, we recruited 90 patients, of whom 43 (48%) were randomly assigned to receive HCO-HD and 47 (52%) were randomly assigned to receive HF-HD. All 90 patients were included in the analysis of the primary outcome. One (2%) patient from the HF-HD group withdrew consent before receiving treatment. During treatment, nine (21%) patients from the HCO-HD group and two (4%) patients in the HF-HD group discontinued trial treatment. After 90 days, 24 (56%) patients in the HCO-HD group and 24 (51%) patients in the HF-HD group were independent from dialysis (relative risk 1·09, 95% CI 0·74-1·61; p=0·81). During the 2-year follow-up, 98 serious adverse events were reported in the HCO-HD group and 82 serious adverse events were reported in the HF-HD group. The most common serious adverse events were infections and adverse events related to the cardiovascular and thrombotic and musculoskeletal systems. During the first 90 days, 26 infections were reported in the HCO-HD group and 13 infections were reported in the HF-HD group, including 14 lung infections in the HCO-HD group and three lung infections in the HF-HD group.
INTERPRETATION
In this phase 2 study, HCO-HD did not improve clinical outcomes for patients with de novo multiple myeloma and myeloma cast nephropathy who required haemodialysis for acute kidney injury and who received a bortezomib-based chemotherapy regimen relative to those receiving HF-HD. These results do not support proceeding to a phase 3 study for HCO-HD in these patients.
FUNDING
Gambro, Janssen, and Binding Site
Tuberculosis control in the United States: strengths, weaknesses, opportunities, threats.
No full textLevothyroxine to increase live births in euthyroid women with thyroid antibodies trying to conceive: the TABLET RCT
No full textThe rate of bone loss slows after 1-2 years of initial antiretroviral therapy: final results of the Strategic Timing of Antiretroviral Therapy(START) bone mineral density substudy.
No full textOBJECTIVES
Initial antiretroviral therapy (ART) causes loss of bone mineral density (BMD) over the first 1-2 years. Whether this loss continues with longer therapy is unclear. We determined changes in bone and spine BMD over 5 years in adults receiving immediate or deferred initial ART.
METHODS
In the Strategic Timing of Antiretroviral Therapy (START) BMD substudy, ART-naïve adults with CD4 counts > 500 cells/μL were randomized to immediate or deferred ART. Deferred group participants not yet on ART were offered ART after May 2015. Mean per cent changes in total hip and lumbar spine BMD (measured annually by dual-energy X-ray absorptiometry) were compared between groups using longitudinal mixed models. Fracture rates were also compared between groups for all START participants.
RESULTS
Substudy participants (immediate group, n = 201; deferred group, n = 210; median age 32 years; 80% non-white; 24% female) were followed for a mean 4.5 years until December 2016. In the immediate group, > 96% used ART throughout. In the deferred group, 16%, 58% and 94% used ART at years 1, 3 and 5, respectively. BMD decreased more in the immediate group initially; groups had converged by year 3 at the spine and year 4 at the hip by intent-to-treat (ITT). BMD changes after year 1 were similar in the immediate group and in those off ART in the deferred group [mean difference: spine, 0.03% per year; 95% confidence interval (CI) -0.4, 0.4; P = 0.88; hip, -0.2% per year; 95% CI -0.7, 0.3; P = 0.37]. Fracture incidence did not differ significantly between groups (immediate group, 0.86/100 person-years versus deferred group, 0.85/100 person-years; hazard ratio 1.01; 95% CI 0.76, 1.35; P = 0.98).
CONCLUSIONS
Significant ART-induced bone loss slowed after the first year of ART and became similar to that in untreated HIV infection
Hepatocytes Delete Regulatory T Cells by Enclysis, a CD4 T Cell Engulfment Process.
No full textCD4 T cells play critical roles in directing immunity, both as T helper and as regulatory T (Treg) cells. Here, we demonstrate that hepatocytes can modulate T cell populations through engulfment of live CD4 lymphocytes. We term this phenomenon enclysis to reflect the specific enclosure of CD4 T cells in hepatocytes. Enclysis is selective for CD4 but not CD8 cells, independent of antigen-specific activation, and occurs in human hepatocytes in vitro, ex vivo, and in vivo. Intercellular adhesion molecule 1 (ICAM-1) facilitates T cell early adhesion and internalization, whereas hepatocytes form membrane lamellipodia or blebs to mediate engulfment. T cell internalization is unaffected by wortmannin and Rho kinase inhibition. Hepatocytes engulf Treg cells more efficiently than non-Treg cells, but Treg cell-containing vesicles preferentially acidify overnight. Thus, enclysis is a biological process with potential effects on immunomodulation and opens a new field for research to fully understand CD4 T cell dynamics in liver inflammation
Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up.
No full textPrimary hyperoxaluria type 2 is a rare inherited disorder of glyoxylate metabolism causing nephrocalcinosis, renal stone formation and ultimately kidney failure. Previously, primary hyperoxaluria type 2 was considered to have a more favorable prognosis than primary hyperoxaluria type 1, but earlier reports are limited by low patient numbers and short follow up periods. Here we report on the clinical, genetic, and biochemical findings from the largest cohort of patients with primary hyperoxaluria type 2, obtained by a retrospective record review of genetically confirmed cases in the OxalEurope registry, a dataset containing 101 patients from eleven countries. Median follow up was 12.4 years. Median ages at first symptom and diagnosis for index cases were 3.2 years and 8.0 years, respectively. Urolithiasis was the most common presenting feature (82.8% of patients). Genetic analysis revealed 18 novel mutations in the GRHPR gene. Of 238 spot-urine analyses, 23 (9.7%) were within the normal range for oxalate as compared to less than 4% of 24-hour urine collections. Median intra-individual variation of 24-hour oxalate excretion was substantial (34.1%). At time of review, 12 patients were lost to follow-up; 45 of the remaining 89 patients experienced chronic kidney disease stage 2 or greater and 22 patients had reached stage 5. Median renal survival was 43.3 years, including 15 kidney transplantations in 11 patients (1 combined with liver transplantation). Renal outcome did not correlate with genotype, biochemical parameters or initially present nephrocalcinosis. Thus, primary hyperoxaluria type 2 is a disease with significant morbidity. Accurate diagnosis by 24-hour urine analysis and genetic testing are required with careful follow-up
Impact of neuroendocrine morphology on cancer outcomes and stage at diagnosis: a UK nationwide cohort study 2013-2015.
No full textBACKGROUND
The diagnosis of neuroendocrine neoplasms (NENs) is often delayed. This first UK population-based epidemiological study of NENs compares outcomes with non-NENs to identify any inequalities.
METHODS
Age-standardised incidence rate (ASR), 1-year overall survival, hazard ratios and standardised mortality rates (SMRs) were calculated for all malignant NENs diagnosed 2013-2015 from UK national Public Health records. Comparison with non-NENs assessed 1-year overall survival (1YS) and association between diagnosis at stage IV and morphology.
RESULTS
A total of 15,222 NENs were identified, with an ASR (2013-2015 combined) of 8.6 per 100,000 (95% CI 8.5-8.7); 4.6 per 100 000 (95% CI, 4.5-4.7) for gastro-entero-pancreatic (GEP) NENs. The 1YS was 75% (95% CI, 73.9-75.4) varying significantly by sex. Site and morphology were prognostic. NENs (predominantly small cell carcinomas) in the oesophagus, bladder, prostate, and female reproductive organs had a poorer outcome and were three times more likely to be diagnosed at stage IV than non-NENs.
CONCLUSION
Advanced stage at diagnosis with significantly poorer outcomes of some NENs compared with non-NENs at the same anatomical site, highlight the need for improved access to specialist services and targeted service improvement
Role of the intestinal microbiome in colorectal cancer surgery outcomes.
No full textOBJECTIVES
Growing evidence supports the role of the intestinal microbiome in the carcinogenesis of colorectal cancers, but its impact on colorectal cancer surgery outcomes is not clearly defined. This systematic review aimed to analyze the association between intestinal microbiome composition and postoperative complication and survival following colorectal cancer surgery.
METHODS
A systematic review was conducted according to the 2009 PRISMA guidelines. Two independent reviewers searched the literature in a systematic manner through online databases, including Medline, Scopus, Embase, Cochrane Oral Health Group Specialized Register, ProQuest Dissertations and Theses Database, and Google Scholar. Human studies investigating the association between the intestinal microbiome and the short-term (anastomotic leakage, surgical site infection, postoperative ileus) and long-term outcomes (cancer-specific mortality, overall and disease-free survival) of colorectal cancer surgery were selected. Patients with any stage of colorectal cancer were included. The Newcastle-Ottawa scale for case-control and cohort studies was used for the quality assessment of the selected articles.
RESULTS
Overall, 8 studies (7 cohort studies and 1 case-control) published between 2014 and 2018 were included. Only one study focused on short-term surgical outcomes, showing that anastomotic leakage is associated with low microbial diversity and abundance of Lachnospiraceae and Bacteroidaceae families in the non-cancerous resection lines of the stapled anastomoses of colorectal cancer patients. The other 7 studies focused on long-term oncological outcomes, including survival and cancer recurrence. The majority of the studies (5/8) found that a higher level of Fusobacterium nucleatum adherent to the tumor tissue is associated with worse oncological outcomes, in particular, increased cancer-specific mortality, decreased median and overall survival, disease-free and cancer-specific survival rates. Also a high abundance of Bacteroides fragilis was found to be linked to worse outcomes, whereas the relative abundance of the Prevotella-co-abundance group (CAG), the Bacteroides CAG, and the pathogen CAG as well as Faecalibacterium prausnitzii appeared to be associated with better survival.
CONCLUSIONS
Based on the limited available evidence, microbiome composition may be associated with colorectal cancer surgery outcomes. Further studies are needed to elucidate the role of the intestinal microbiome as a prognostic factor in colorectal cancer surgery and its possible clinical implications