Assessing Circulating Tumour DNA (ctDNA) as a Biomarker for Anal Cancer Management: A Systematic Review.

This systematic review investigates the potential of circulating tumour DNA (ctDNA) as a predictive biomarker in the management and prognosis of squamous cell carcinoma of the anal canal (SCCA). PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials were searched until 7 January 2024. Selection criteria included research articles exploring ctDNA in the context of anal cancer treatment response, recurrence risk assessment, and consideration of salvage surgery. A total of eight studies were therefore included in the final review, examining a total of 628 patients. These studies focused on three main themes: SCCA diagnosis and staging, treatment response, and patient outcomes. Significant heterogeneity was observed in terms of patient cohort, study methodology, and ctDNA biomarkers. Four studies provided information on the sensitivity of ctDNA biomarkers in SCCA, with a range of 82-100%. Seven studies noted a correlation between pre-treatment ctDNA levels and SCCA disease burden, suggesting that ctDNA could play a role as a biomarker for the staging of SCCA. Across all seven studies with paired pre- and post-treatment ctDNA samples, a trend was seen towards decreasing ctDNA levels post-treatment, with specific identification of a 'fast elimination' group who achieve undetectable ctDNA levels prior to the end of treatment and may be less likely to experience treatment failure. Residual ctDNA detection post-treatment was associated with poorer patient prognosis. This systematic review identifies the broad potential of ctDNA as a useful and decisive tool in the management of SCCA. Further analysis of ctDNA biomarkers that include larger patient cohorts is required in order to clearly evaluate their potential role in clinical decision-making processes.

Primary closure versus vertical rectus abdominis myocutaneous (VRAM) flap closure of perineal wound following abdominoperineal resection-a systematic review and meta-analysis.

PURPOSE/AIM: Perianal wound healing and/or complications are common following abdominoperineal resection (APR). Although primary closure is commonly undertaken, myocutaneous flap closure such as vertical rectus abdominis myocutaneous flap (VRAM) is thought to improve wound healing process and outcome. A comprehensive meta-analysis was performed to compare outcomes of primary closure versus VRAM flap closure of perineal wound following APR. METHODS: PubMed, MEDLINE, EMBASE, and Cochrane Central Registry of Controlled Trials were comprehensively searched until the 8th of August 2023. Included studies underwent meta-analysis to compare outcomes of primary closure versus VRAM flap closure of perineal wound following APR. The primary outcome of interest was perineal wound complications, and the secondary outcomes were abdominal wound complications, dehiscence, wound healing time, length of hospital stay, and mortality. RESULTS: Ten studies with 1141 patients were included. Overall, 853 patients underwent primary closure (74.8%) and 288 patients underwent VRAM (25.2%). Eight studies reported on perineal wound complications after APR: 38.2% (n = 263/688) in the primary closure group versus 32.8% (n = 80/244) in the VRAM group. Perineal complication rates were statistically significantly lower in the VRAM group versus primary closure ((M-H OR, 1.61; 95% CI 1.04-2.49;

Epidemiology of mammary tumours in bitches under veterinary care in the UK in 2016.

BACKGROUND: There is limited information on the epidemiology of canine mammary tumours. This study aimed to estimate the incidence and risk factors for mammary tumours in UK bitches. METHODS: A nested case-control study was conducted within VetCompass to estimate the frequency and risk factors for clinically diagnosed mammary tumours during 2016 (VetCompass study). A second case-control study explored further breed associations for cases confirmed histopathologically compared to the VetCompass controls (laboratory study). Multivariable logistic regression was used to evaluate associations between risk factors and mammary tumours. RESULTS: The incidence of mammary tumours was 1340.7/100,000 per year (95% confidence interval: 1198.1-1483.3). A total of 222 clinical cases (VetCompass study) and 915 laboratory cases (laboratory study) were compared to 1515 VetCompass controls in the two analyses. In the VetCompass study, Springer and Cocker Spaniels, Boxers, Staffordshire Bull Terriers and Lhasa Apsos had increased odds of developing mammary tumours. Neutering was associated with reduced odds, while odds increased with increasing age and a history of pseudopregnancy. In the laboratory study, increasing age was associated with greater odds of mammary tumours, and the breeds most at risk were similar to those identified in the VetCompass study. LIMITATIONS: The timing of neutering was not consistently available. Comparing laboratory cases to VetCompass controls provided only exploratory evidence for the breed associations identified. CONCLUSIONS: The study provides an update on the frequency of canine mammary tumours.

Impact of the 12-gene recurrence score in influencing adjuvant chemotherapy prescription in mismatch repair proficient stage II/III colonic carcinoma-a systematic review and meta-analysis.

INTRODUCTION: The 12-gene recurrence score (RS) is a clinically validated assay which predicts recurrence risk in patients with stage II/III colon cancer. Decisions regarding adjuvant chemotherapy may be guided using this assay or based on the judgement of tumour board. AIMS: To assess the concordance between the RS and MDT decisions regarding adjuvant chemotherapy in colon cancer. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Meta-analyses were performed using the Mantel-Haenszel method using the Review Manager version 5.4 software. RESULTS: Four studies including 855 patients with a mean age of 68 years (range: 25-90 years) met inclusion criteria. Overall, 79.2% had stage II disease (677/855) and 20.8% had stage III disease (178/855). For the entire cohort, concordant results between the 12-gene assay and MDT were more likely than discordant (odds ratio (OR): 0.38, 95% confidence interval (CI): 0.25-0.56, P < 0.001). Patients were more likely to have chemotherapy omitted than escalated when using the RS (OR: 9.76, 95% CI: 6.72-14.18, P < 0.001). For those with stage II disease, concordant results between the 12-gene assay and MDT were more likely than discordant (OR: 0.30, 95% CI: 0.17-0.53, P < 0.001). In stage II disease, patients were more likely to have chemotherapy omitted than escalated when using the RS (OR: 7.39, 95% CI: 4.85-11.26, P < 0.001). CONCLUSIONS: The use of the 12-gene signature refutes the decision of tumour board in 25% of cases, with 75% of discordant decisions resulting in omission of adjuvant chemotherapy. Therefore, it is possible that a proportion of such patients are being overtreated when relying on tumour board decisions alone.

Differential Engagement by Race/Ethnicity in Experimental Trials of Mental Health Treatment Interventions: A Systematic Review.

Objective: Research on mental health interventions, largely from observational studies, suggests that individuals who are Black, Indigenous, and People of Color (BIPOC) have lower treatment engagement than non-Latino Whites. This systematic review focuses on prospective, experimental treatment trials, which reduce variability in patient and intervention characteristics and some access barriers (eg, cost), to examine the association of race/ethnicity and engagement.Data Sources: A systematic search of PubMed and PsycINFO through May 2020 using terms covering mental health treatment, engagement, and race/ethnicity.Study Selection: US-based, English-language, prospective experimental (including quasi-experimental) trials of adults treated for DSM-defined mental disorders were included. Studies had to compare engagement (treatment initiation and retention, medication adherence) across 2 or more ethnoracial groups. Fifty-five of 2,520 articles met inclusion criteria.Data Extraction: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Collaboration bias-risk assessment tool were used to report study findings.Results: Twenty-nine articles (53%) reported significant ethnoracial engagement differences, of which 93% found lower engagement among BIPOC groups compared largely to non-Latino Whites. The proportion of significant findings was consistent across quality of studies, covariate adjustments, ethnoracial groups, disorders, treatments, and 4 engagement definitions. Reporting limitations were found in covariate analyses and disaggregation of results across specific ethnoracial groups.Conclusions: Prospective experimental treatment trials reveal consistently lower BIPOC engagement, suggesting persisting disparities despite standardized study designs. Future research should improve inclusion of understudied groups, examine covariates systematically, and follow uniform reporting and analytic practices to elucidate reasons for these disparities.

Sarcopaenia, obesity, sarcopaenic obesity and outcomes following hepatic resection for colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: Obesity is a risk factor for the development of colorectal cancer. Limited evidence exists about outcomes for obese patients undergoing hepatic resection for colorectal liver metastases (CRLM). Sarcopaenia is characterised by a decline in muscle function and muscle mass. It is associated with poorer outcomes for patients on chemotherapy, but there are limited data for sarcopaenic patients undergoing hepatic resection for CRLM. METHODS: Pubmed, Embase, Cochrane Central, Web of Science, SCOPUS, and CINAHL databases were searched for articles which were selected in accordance with PRISMA guidelines. Primary outcomes were overall survival (OS) and disease-free survival (DFS). A random effects meta-analysis was conducted. RESULTS: Thirteen studies were included incorporating 2936 patients. No significant difference was found between obese and non-obese patients in OS (HR 0.81, CI 0.47-1.39, p = 0.44) or DFS (HR 1.0, CI 0.99-1.01, p = 0.98). Sarcopaenia was associated with worse OS (HR 1.65, CI 1.10-2.48, p = 0.01), and increased major post operative complications (OR 1.91, CI 1.16-3.14, p = 0.01). Only one study examined outcomes for sarcopaenic obese patients. CONCLUSION: Limited evidence exists describing the impact of obesity and sarcopenia on outcomes following hepatic resection for CRLM. Obese patients do not have worse oncological outcomes, whereas sarcopaenia is associated with poorer long-term survival.

The impact of COVID-19 on emergency surgical presentations in a university teaching hospital.

INTRODUCTION: The Coronavirus-19 (COVID-19) pandemic has led to a 50-70% reduction in acute non-COVID-19 presentations to emergency departments globally. AIM: To determine the impact of COVID-19 on incidence, severity, and outcomes of acute surgical admissions in an Irish University teaching hospital. METHODS: Descriptive data concerning patients presenting with acute appendicitis, diverticulitis, and cholecystitis were analysed and compared from March-May 2020 to March-May 2019. RESULTS: Acute surgical admissions decreased in March from 191 (2020) to 55 (2019) (55%), before increasing by 28% in April (2019: 119, 2020: 153). Admissions due to acute cholecystitis reduced by 33% (2019: 33, 2020: 22), with increased severity at presentation (P = 0.079) and higher 30-day readmission rates (P = 0.056) reported. Acute appendicitis presentations decreased by 44% (2019: 78, 2020: 43, P = 0.019), with an increase in severity (P < 0.001), conservative management (P < 0.001), and post-operative complications (P = 0.029) in 2020 compared to the same period in 2019. CONCLUSION: COVID-19 has potentiated a significant reduction in acute surgical presentations to our hospital. Patients presenting with acute appendicitis during the pandemic had more severe disease, were more likely to have complications, and were significantly more likely to be managed conservatively when compared to historical data.

Improving Communication Between Nursing Staff and On-Call Residents via a Standardized Paging Protocol.

OBJECTIVES: Clear and efficient communication between nursing staff and medical providers is an essential component of healthcare delivery. At McLean Hospital, there is an inconsistency in utilization of alphanumeric paging, with many individuals communicating primarily via numeric-only pages that can cause difficulty in triaging importance of pages and lead to disruptions in care. This quality improvement project sought to improve communication between nursing staff and residents by decreasing the number of difficult to triage pages sent to the psychiatrist-on-call at a stand-alone academic psychiatric hospital. METHODS: Pages were analyzed during two discrete month-long periods before and after the implementation of a standardized paging protocol, which included an updated online template asking the individual sending the page to include specific information (urgency of page, identifying information of patient, contact information, and name of sender) and dissemination of information on its use. RESULTS: The implementation of this protocol resulted in a statistically significant decrease in the percentage of pages that were difficult to triage (22.1 to 15.0%; p < 0.05). Examining specific units in the hospital revealed significant variation of change, with as much as 40% reduction to as large as an 11% increase in difficult to triage pages. CONCLUSIONS: The decrease in the percentage of difficult to triage pages suggests that a standard paging protocol can improve delivery of patient care by minimizing interruptions with low-priority pages and may improve quality of communication between nursing staff and physicians on-call, ultimately improving quality of care provided and bettering the resident learning environment.

Repair of microdamage caused by cyclic loading in insect cuticle.

It is well known that repeated loading cycles can reduce the strength of a material and cause eventual failure by the gradual build-up of damage. Previous work has shown that mammalian bone is able to extend its life almost indefinitely by continuously repairing microdamage, preventing the development of macroscopic cracks. However, no study has been conducted until now to investigate repair of microdamage in any other biological material. We applied cyclic bending loads to the hind tibiae of desert locusts (Schistocerca gregaria). We observed a significant decrease in the elastic stiffness (Young's modulus) of the cuticle during the five applied loading cycles, indicating that microdamage had been induced. The tibiae were then left to rest for various time periods: 1 hr, 24 hr, 1 week, and 4 weeks. When tested again after up to 24 hr, there was still a significant decrease in stiffness, showing that some microdamage remained. However, in the samples left for 1 week or 4 weeks before retesting, this decrease in stiffness had disappeared, indicating that the microdamage had been repaired. This is the first ever indication that insects are capable of repairing microdamage. It is a highly significant finding-insects such as locusts rely on the stiffness and strength of their hind legs for jumping. This study suggests that, within a time period of order of a few days, the insect can fully restore the mechanical function of an overloaded leg and thus return to normal activities.

The surgical management of severe dentofacial infections (DFI)-a prospective study.

Dentofacial infections (DFI) lead to morbidity and rarely, mortality. We hypothesised that certain clinical and laboratory parameter factors may be associated with a more severe course and an increased length of stay. We designed a prospective study that included all patients admitted with a DFI to the Oral and Maxillofacial Department between July 2014 and July 2015. A total of 125 were enrolled. We found that serum concentration of CRP on admission and increasing number of fascial spaces involved by the infection were significant predictors of hospital stay (p = 0.02 and p = 0.01, respectively). The average length of stay for a dentofacial infection requiring admission was 4.5 days. Most patients require surgical intervention in combination with intravenous antibiotics for successful resolution. Improved and timely access to primary dental care is likely to reduce the burden for patients their families and the acute hospital service as a consequence of advanced DFI.

Age-related responses to injury and repair in insect cuticle.

We evaluated the ability of female adult desert locusts (Schistocerca gregaria) to repair injuries to their exoskeletons and restore mechanical strength over the course of their natural life. We discovered that younger insects are more capable of repairing injuries, displaying no significant decreases in failure strength, stiffness or bending moment to failure after 3 weeks of repair. Older insects, in contrast, were only capable of repairing to ∼70% of their original strength. Both older and younger insects carry out targeted deposition to repair injuries. We also examined different mechanisms of failure, and we discovered that the cuticle of older insects is more susceptible to crack growth due to a large decrease in fracture toughness with age, making them more sensitive to scalpel cuts and punctures. The biological mechanisms that drive these changes are still under investigation.

The HIV Workforce in New York State: Does Patient Volume Correlate with Quality?

BACKGROUND: Knowledge of care practices among clinicians who annually treat <20 human immunodeficiency virus (HIV)-positive patients with antiretroviral therapy (ART) is insufficient, despite their number, which is likely to increase given shifting healthcare policies. We analyze the practices, distribution and quality of care provided by low-volume prescribers (LVPs) based on available data sources in New York State. METHODS: We communicated with 1278 (66%) of the LVPs identified through a statewide claims database to determine the circumstances under which they prescribed ART in federal fiscal year 2009. We reviewed patient records from 84 LVPs who prescribed ART routinely and compared their performance with that of experienced clinicians practicing in established HIV programs. RESULTS: Of the surveyed LVPs, 368 (29%) provided routine ambulatory care for 2323 persons living with HIV/AIDS, and 910 LVPs cited other reasons for prescribing ART. Although the majority of LVPs (73%) practiced in New York City, patients living upstate were more likely to be cared for by a LVP (odds ratio, 1.7; 95% confidence interval, 1.4-1.9). Scores for basic HIV performance measures, including viral suppression, were significantly higher in established HIV programs than for providers who wrote prescriptions for <20 persons living with HIV/AIDS (P < .01). We estimate that 33% of New York State clinicians who provide ambulatory HIV care are LVPs. CONCLUSIONS: Our findings suggest that the quality of care associated with providers who prescribe ART for <20 patients is lower than that provided by more experienced providers. Access to experienced providers as defined by patient volume is an important determinant of delivering high-quality care and should guide HIV workforce policy decisions.

Engineering and application of P450 monooxygenases in pharmaceutical and metabolite synthesis.

Cytochrome P450 monoxygenase (P450s or CYPs) allow access to drug metabolites, necessary for approval of new therapeutics in one step, with increased success being demonstrated using bacterial and fungal P450s. Moreover, 12 of the 13 products of the human metabolism of verapamil can be accessed through engineered and chimeric bacterial P450s. These P450s are also used in the synthesis of pharmaceuticals themselves, including the semi-synthetic production of artemisinin in an engineered cell. The integration of new technologies including ultrasound and polyfluorinated hydrocarbon solvents offers an attractive means by the true synthetic potential of ubiquitous P450s can be fully realised.

Ionic liquids--media for unique phosphorus chemistry.

Ionic liquids have been shown to offer hitherto unseen control as both a storage solvent for PCl3 and POCl3 and reaction media for fluorination and mixed anhydride formation under benign conditions.