Preoperative chemotherapy response and survival in patients with colorectal cancer peritoneal metastases.

Treatment guidelines provided by PRODIGE-7 recommend perioperative systemic chemotherapy before cytoreductive surgery (CRS) for colorectal cancer peritoneal metastases (CRPM). Toxicity with multimodal treatment needs to be better defined. Chemotherapy response and impact on survival have not been reported. We assessed CRPM patients who received systemic oxaliplatin/irinotecan before CRS (preoperative) with Mitomycin C (35 mg/m2, 90 min) or Oxaliplatin (368 mg/m2, 30 min) heated intraperitoneal chemotherapy (HIPEC). Secondary analysis was performed from a prospective database. Overall survival (OS) in chemotherapy responders (R) and nonresponders (NR) was compared. Toxicity was assessed by rate of adverse events (AEs). From April 2005 to April 2021, 436 patients underwent CRS + HIPEC; 125 (29%) received preoperative chemotherapy. The 112 (90%) received oxaliplatin (64, 57%) or irinotecan (48, 43%). R, defined as complete (CR) or partial response on preoperative imaging and/or postoperative histology, was seen in 71, 63% (53.8-72.3); 16, 14% (8.4-22.2) had CR. Median OS in R versus NR was 43.7 months (37.9-49.4) versus 23.9 (16.3-31.4) p = 0.007, HR 0.51 (0.31-0.84). OS multivariable analysis showed HR 0.48 (0.25-0.95), p = 0.03 for chemotherapy response corrected by peritoneal cancer index, completeness of cytoreduction score. CRS led to 21% grade 3-4 AEs versus 4% for preoperative chemotherapy. HIPEC grade 3-4 AEs were 0.5%. Preoperative chemotherapy response is an independent predictor for OS in CRPM.

A polygenic risk score added to a QRISK®2 cardiovascular disease risk calculator demonstrated robust clinical acceptance and clinical utility in the primary care setting.

AIMS: The aim of the study was to assess the real-world feasibility, acceptability, and impact of an integrated risk tool for cardiovascular disease (CVD IRT, combining the standard QRISK®2 risk algorithm with a polygenic risk score), implemented within routine primary practice in the UK National Health Service. METHODS AND RESULTS: The Healthcare Evaluation of Absolute Risk Testing Study (NCT05294419) evaluated participants undergoing primary care health checks. Both QRISK2 and CVD IRT scores were returned to the healthcare providers (HCPs), who then communicated the results to participants. The primary outcome of the study was feasibility of CVD IRT implementation. Secondary outcomes included changes in CVD risk (QRISK2 vs. CVD IRT) and impact of the CVD IRT on clinical decision-making. A total of 832 eligible participants (median age 55 years, 62% females, 97.5% White ethnicity) were enrolled across 12 UK primary care practices. Cardiovascular disease IRT scores were obtained on 100% of the blood samples. Healthcare providers stated that the CVD IRT could be incorporated into routine primary care in a straightforward manner in 90.7% of reports. Participants stated they were 'likely' or 'very likely' to recommend the use of this test to their family or friends in 86.9% of reports. Participants stated that the test was personally useful (98.8%) and that the results were easy to understand (94.6%). When CVD IRT exceeded QRISK2, HCPs planned changes in management for 108/388 (27.8%) of participants and 47% (62/132) of participants with absolute risk score changes of >2%. CONCLUSION: Amongst HCPs and participants who agreed to the trial of genetic data for refinement of clinical risk prediction in primary care, we observed that CVD IRT implementation was feasible and well accepted. The CVD IRT results were associated with planned changes in prevention strategies.

When a standard cardiovascular risk tool, as currently used in National Health Service Health Checks, was expanded to include genetic risk information, it was well accepted by both participants and healthcare providers and generated impactful changes in planned clinical decision-making.Most participants found the test useful and easy to understand, and healthcare providers found it straightforward to use in most cases.When risk was increased by the addition of genetic information, this influenced planned management decisions.

Comparison of metagenomic and targeted methods for sequencing human pathogenic viruses from wastewater.

Wastewater-based epidemiology is a powerful tool for monitoring the emergence and spread of viral pathogens at the population scale. Typical polymerase chain reaction (PCR)-based methods of quantitative and genomic monitoring of viruses in wastewater provide high sensitivity and specificity. However, these methods are limited to the surveillance of target viruses in a single assay and require prior knowledge of the target genome(s). Metagenomic sequencing methods may represent a target-agnostic approach to viral wastewater monitoring, allowing for the detection of a broad range of target viruses, including potentially novel and emerging pathogens. In this study, targeted and untargeted metagenomic sequencing methods were compared with tiled-PCR sequencing for the detection and genotyping of viral pathogens in wastewater samples. Deep shotgun metagenomic sequencing was unable to generate sufficient genome coverage of human pathogenic viruses for robust genomic epidemiology, with samples dominated by bacteria. Hybrid-capture enrichment of shotgun libraries for respiratory viruses led to significant increases in genome coverage for a range of targets. Tiled-PCR sequencing led to further improvements in genome coverage compared to hybrid capture for severe acute respiratory syndrome coronavirus 2, enterovirus D68, norovirus GII, and human adenovirus F41 in wastewater samples. In conclusion, untargeted shotgun sequencing was unsuitable for genomic monitoring of the low virus concentrations in wastewater samples analyzed in this study. Hybrid-capture enrichment represented a viable method for simultaneous genomic epidemiology of a range of viral pathogens, while tiled-PCR sequencing provided the optimal genome coverage for individual viruses with the minimum sequencing depth. IMPORTANCE Most public health initiatives that monitor viruses in wastewater have utilized quantitative polymerase chain reaction (PCR) and whole genome PCR sequencing, mirroring techniques used for viral epidemiology in individuals. These techniques require prior knowledge of the target viral genome and are limited to monitoring individual or small groups of viruses. Metagenomic sequencing may offer an alternative strategy for monitoring a broad spectrum of viruses in wastewater, including novel and emerging pathogens. In this study, while amplicon sequencing gave high viral genome coverage, untargeted shotgun sequencing of total nucleic acid samples was unable to detect human pathogenic viruses with enough sensitivity for use in genomic epidemiology. Enrichment of shotgun libraries for respiratory viruses using hybrid-capture technology provided genotypic information on a range of viruses simultaneously, indicating strong potential for wastewater surveillance. This type of targeted metagenomics could be used for monitoring diverse targets, such as pathogens or antimicrobial resistance genes, in environmental samples.

Analysis of the ARTIC V4 and V4.1 SARS-CoV-2 primers and their impact on the detection of Omicron BA.1 and BA.2 lineage-defining mutations.

The ARTIC protocol uses a multiplexed PCR approach with two primer pools tiling the entire SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genome. Primer pool updates are necessary for accurate amplicon sequencing of evolving SARS-CoV-2 variants with novel mutations. The suitability of the ARTIC V4 and updated V4.1 primer scheme was assessed using whole genome sequencing of Omicron from clinical samples using Oxford Nanopore Technology. Analysis of Omicron BA.1 genomes revealed that 93.22 % of clinical samples generated improved genome coverage at 50× read depth with V4.1 primers when compared to V4 primers. Additionally, the V4.1 primers improved coverage of BA.1 across amplicons 76 and 88, which resulted in the detection of the variant-defining mutations G22898A, A26530G and C26577G. The Omicron BA.2 sub-variant (VUI-22JAN-01) replaced BA.1 as the dominant variant by March 2022, and analysis of 168 clinical samples showed reduced coverage across amplicons 15 and 75. Upon further interrogation of primer binding sites, a mutation at C4321T [present in 163/168 (97 %) of samples] was identified as a possible cause of complete dropout of amplicon 15. Furthermore, two mutations were identified within the primer binding regions for amplicon 75: A22786C (present in 90 % of samples) and C22792T (present in 12.5 % of samples). Together, these mutations may result in reduced coverage of amplicon 75, and further primer updates would allow the identification of the two BA.2-defining mutations present in amplicon 75: A22688G and T22679C. This work highlights the need for ongoing surveillance of primer matches as circulating variants evolve and change.

Readmissions after general surgery: a prospective multicenter audit.

BACKGROUND: Readmission rates after surgical procedures are viewed as a marker of quality of care and as a driver to improve outcomes in the United Kingdom, they are not remunerated. However, readmissions are not wholly avoidable. The aim of this study was to develop a regional overview of readmissions to determine the proportion that might be avoidable and to examine predictors of readmissions at a unit level. METHODS: We undertook a prospective multicenter audit of readmissions following National Health Service funded general surgical procedures in five National Health Service hospitals and three independent sector providers over a 2-wk period. Basic demographic and procedure data were captured. Readmissions to hospitals were identified through acute admissions lists. Reason for readmission was identified, and the readmission data assessed by a senior surgical doctor as to whether it was avoidable. RESULTS: We identified 752 operations in the study period with all followed up to 30 d. The overall rate of readmissions was 4.7%, with 40% of these judged as being potentially avoidable. Pain and wound problems accounted for the vast majority of avoidable readmissions. The number of unavoidable readmissions was correlated with the workload of each center (r = 0.63, P = 0.06) and as with the higher (British United Provident Association) complexity of surgery (r = 0.90, P = 0.01). Patient and demographic factors were not associated with readmissions. CONCLUSIONS: This prospective audit describes readmission rates after general surgery. Volume and complexity of work are associated with readmission rates. A large proportion of readmissions could be reduced by attention to analgesia and outpatient arrangements for wound management.

Has the Bachelor of Surgery Left Medical School?-A National Undergraduate Assessment.

INTRODUCTION: Nearly all trainee doctors would undertake a surgical placement in their clinical training; however, there is anecdotal evidence of variability in undergraduate surgical teaching across the UK. We set out to describe the provision of undergraduate surgery and report graduating students' opinions of aspects of this. METHODS: We undertook a cross-sectional questionnaire of medical students graduating in 2014 from UK medical schools. An online electronic questionnaire was used to capture demographics, career intentions, and individual's undergraduate experience of surgery. A separate questionnaire was sent to medical schools to assess time devoted to surgical placements and how surgical sciences were taught and assessed. RESULTS: From 483 responses covering 31 UK medical schools, there were 328 completed student questionnaires. A third of respondents felt that teaching of surgical sciences was inadequate. Medical schools reported time allocated to surgical specialties ranging from 4 to 21 weeks (median 13 weeks). Among all, 1 medical school offered a basic surgical skills course and 1 medical school specifically assessed surgical-related skills. Overall, 65% of medical students felt prepared for a surgical foundation placement and 88% felt prepared for a medical foundation placement. In total, 78% felt ready to participate in an acute medicine on-call and 48% felt ready for emergency surgery on-call. There was a positive association between time dedicated to undergraduate surgery and reported preparedness for a foundation surgical job. CONCLUSIONS: UK medical students reported uniformly low rates of satisfaction with surgical science teaching. Students studying at medical schools with more time in the curriculum dedicated to surgery reported higher levels of preparedness for surgical foundation jobs. There were differences in the rates of perceived preparedness for surgical posts and for emergency surgery. There is a clear need to review undergraduate surgical provision to ensure that students are equipped for safe practice in junior surgical foundation jobs.

Assessing the Nontechnical Skills of Surgical Trainees: Views of the Theater Team.

OBJECTIVE: This study aims to explore the views of members of theater teams regarding the proposed introduction of a workplace-based assessment of nontechnical skills of surgeons (NOTSS) into the Intercollegiate Surgical Curriculum Programme in the United Kingdom. In addition, the previous training and familiarity of the members of the surgical theater team with the concept and assessment of NOTSS would be evaluated. DESIGN: A regional survey of members of theater teams (consultant surgeons, anesthetists, scrub nurses, and trainees) was performed at 1 teaching and 2 district general hospitals in South Yorkshire. RESULTS: There were 160 respondents corresponding to a response rate of 81%. The majority (77%) were not aware of the NOTSS assessment tool with only 9% of respondents reporting to have previously used the NOTSS tool and just 3% having received training in NOTSS assessment. Overall, 81% stated that assessing NOTSS was as important as assessing technical skills. Trainees attributed less importance to nontechnical skills than the other groups (p ≤ 0.016). Although opinion appears divided as to whether the presence of a consultant surgeon in theater could potentially make it difficult to assess a trainee's leadership skills and decision-making capabilities, overall 60% agree that the routine use of NOTSS assessment would enhance safety in the operating theater and 80% agree that the NOTSS tool should be introduced to assess the nontechnical skills of trainees in theater. However, a significantly lower proportion of trainees (45%) agreed on the latter compared with the other groups (p = 0.001). CONCLUSIONS: Our survey demonstrates acceptability among the theater team for the introduction of the NOTSS tool into the surgical curriculum. However, lack of familiarity highlights the importance of faculty training for assessors before such an introduction.

Health Education England, Local Education and Training Boards (LETBs) and reform of healthcare education: implications for surgical training.

BACKGROUND: National Health Service (NHS) reforms have changed the structure of postgraduate healthcare education and training. With a Government mandate that promotes multi-professional education and training aligned with policy driven initiatives, this article highlights concerns over the impact that these changes may have on surgical training. DISCUSSION: The creation of Health Education England (HEE) and its local education and training boards (LETBs), which are dominated by NHS healthcare providers, should result in greater accountability of employers in workforce planning, enhanced local responsibility and increased transparency of funding allocation. However, these changes may also create a potential poacher-turned-gamekeeper role of employers, who now have responsibility for junior doctors' training. Analysis of LETB membership reveals a dearth of representation of surgeons, who comprise only 2% of board members, with the input of trainees also seemingly overlooked. A lack of engagement with the LETBs by the independent sector is a concern with increasing numbers of training opportunities potentially being lost as a result.The new system also needs to recognise the specific training needs required by the craft specialties given the demands of technical skill acquisition, in particular regarding the provision of simulation training facilities and trainer recognition. However, training budget cuts may result in a disproportionate reduction of funding for surgical training. Surgical training posts will also be endangered, opportunities for out-of-programme experience and research may also decline and further costs are likely to be passed onto the trainee. SUMMARY: Although there are several facets to the recent reforms of the healthcare education and training system that have potential to improve surgical training, concerns need to be addressed. Engagement from the independent sector and further clarification on how the LETBs will be aligned with commissioning services are also required. Surgical training is in danger of taking a back seat to Government mandated priorities. Representation of trainees and surgeons on LETB committees is essential to ensure a surgical viewpoint so that the training needs of the future consultant workforce meet the demands of a 21st century health service.

A Rare Case of Cholecystitis Caused by Raoultella planticola.

A 62-year-old female presented with right upper quadrant pain. Clinical examination and ultrasound scan were consistent with gallstones and acute cholecystitis. She received 3 days of intravenous Co-amoxiclav and was discharged with 5-days of oral antibiotics with arrangements to return for an elective cholecystectomy. This was performed 5 months later which revealed an inflamed gallbladder and a localised abscess secondary to gallbladder perforation. Fluid from the gallbladder was taken which cultured Raoultella planticola, a gram-negative, nonmotile environmental bacteria (Bagley et al. (1981)). This is the first report of biliary sepsis with a primary infection by R. planticola. This patient was treated with a 5-day course of oral Co-amoxiclav and made a full recovery.

Neuropilins: expression and roles in the epithelium.

Initially found expressed in neuronal and then later in endothelial cells, it is well established that the transmembrane glycoproteins neuropilin-1 (NRP1) and neuropilin-2 (NRP2) play essential roles in axonal growth and guidance and in physiological and pathological angiogenesis. Neuropilin expression and function in epithelial cells has received little attention when compared with neuronal and endothelial cells. Overexpression of NRPs is shown to enhance growth, correlate with invasion and is associated with poor prognosis in various tumour types, especially those of epithelial origin. The contribution of NRP and its ligands to tumour growth and metastasis has spurred a strong interest in NRPs as novel chemotherapy drug targets. Given NRP's role as a multifunctional co-receptor with an ability to bind with disparate ligand families, this has sparked new areas of research implicating NRPs in diverse biological functions. Here, we review the growing body of research demonstrating NRP expression and role in the normal and neoplastic epithelium.

Adenocarcinoma of a colostomy following abdominoperineal resection for squamous cell carcinoma of the anal canal: a case study.

Malignant neoplasms presenting on a stoma, as well as the development of colorectal adenocarcinoma after previous treatment for squamous cell carcinoma (SCC) of the anal canal, are rare. The unique case is presented of an 81-year-old woman with parastomal bleeding and ulceration found to have a primary colorectal adenocarcinoma arising de novo on a colostomy, formed after salvage abdominoperineal resection (APR) 3 years earlier for recurrent anal SCC. This is the first reported case of a colonic adenocarcinoma on a colostomy formed after an APR for anal SCC. Although stomal neoplasia is rare, the appearance of a friable bleeding lesion on the stoma should be investigated to exclude metastatic cancer or a second primary malignancy.

Jejunal diverticulitis.

Although uncommon, jejunoileal diverticula are associated with significant morbidity and mortality. Both acute and chronic symptoms can be varied and non-specific, making jejunoileal diverticular disease a diagnostic and therapeutic challenge. We report a case of jejunal diverticular disease, complicated by acute diverticulitis, in a 75-year-old male who was successfully treated with conservative approach. The non-surgical approach was enabled by early assessment with multislice CT and active close observation.