Provision of acute oncology services in the UK: data from the Society for Acute Medicine Benchmarking Audit 2022 (SAMBA22).

Acute oncology services (AOS) manage acute cancer-related presentations alongside acute medical teams. This study assessed AOS provision against national peer review measures and the burden of acute cancer-related admissions. The 2022 Society for Acute Medicine Benchmarking Audit surveyed UK hospitals, collecting hospital-level and patient-level data for all medical admissions over a 24-h period. Logistic regression models were constructed to identify differences in patient outcomes for cancer-related admissions. Most hospitals (n=120 or 91.6%) reported having an AOS. There was heterogeneity in AOS provision, with many failing to meet peer-review measures. Of the 7,116 patients, 542 (7.6%) were cancer-related admissions. Cancer-related admissions had greater clinical acuity (p<0.05), length of stay (p<0.001) and 14-day mortality (adjusted odds ratio (OR)=3.54, 95% confidence interval (CI): 2.41-5.22, p<0.001) compared with other medical admissions. Increasing availability of AOS with integration of ambulatory pathways are vital next steps to improving care for acute cancer-related admissions.

Targeting DNA damage repair precision medicine strategies in cancer.

DNA repair targeted therapeutics is a promising precision medicine strategy in cancer. The development and clinical use of PARP inhibitors has transformed lives for many patients with BRCA germline deficient breast and ovarian cancer as well as platinum sensitive epithelial ovarian cancers. However, lessons learnt from the clinical use of PARP inhibitors also confirm that not all patients respond either due to intrinsic or acquired resistance. Therefore, the search for additional synthetic lethality approaches is an active area of translational and clinical research. Here, we review the current clinical state of PARP inhibitors and other evolving DNA repair targets including ATM, ATR, WEE1 inhibitors and others in cancer.

The Current Status of DNA-Repair-Directed Precision Oncology Strategies in Epithelial Ovarian Cancers.

Survival outcomes for patients with advanced ovarian cancer remain poor despite advances in chemotherapy and surgery. Platinum-based systemic chemotherapy can result in a response rate of up to 80%, but most patients will have recurrence and die from the disease. Recently, the DNA-repair-directed precision oncology strategy has generated hope for patients. The clinical use of poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA germ-line-deficient and/or platinum-sensitive epithelial ovarian cancers has improved survival. However, the emergence of resistance is an ongoing clinical challenge. Here, we review the current clinical state of PARP inhibitors and other clinically viable targeted approaches in epithelial ovarian cancers.

Reducing incidence of postoperative acute kidney injury in trauma and orthopaedics patients: a quality improvement project.

BACKGROUND: Acute kidney injury (AKI) is a common postoperative complication which increases morbidity and mortality. This quality improvement project aimed to implement measures targeting known risk factors to decrease the incidence of postoperative AKI in trauma and orthopaedics (T&O) patients. METHODS: Data were collected across three six-month to 7-month cycles between 2017 and 2020, analysing all elective and emergency T&O operated patients within a single NHS Trust (n=714, 1008 and 928, respectively). Patients who developed a postoperative AKI were identified using biochemical criteria and data were collected on known AKI risk factors, including use of nephrotoxic medications, and patient outcomes. In the final cycle, the same variables were collected for patients without AKI. Between cycles, measures implemented included: preoperative and postoperative medication reconciliation aiming to stop nephrotoxic medications, orthogeriatrician review of high-risk patients and junior doctor teaching on fluid therapy. Statistical analysis was undertaken to determine the incidence of postoperative AKI across cycles, prevalence of risk factors and impact on length of hospital stay and postoperative mortality. RESULTS: There was a statistically significant decrease in postoperative AKI incidence from 4.27% (43 of 1008 patients) in cycle 2 to 2.05% (19 of 928) in cycle 3 (p=0.006), with a notable decrease in use of nephrotoxic medications. Significant predictors for the development of postoperative AKI included use of diuretics and receiving multiple nephrotoxic drug classes. Development of postoperative AKI significantly increased length of hospital stay by 7.11 days on average (95% CI: 4.84 to 9.38 days, p<0.001) and risk of 1-year postoperative mortality (OR 3.22, 95% CI: 1.03 to 10.55, p=0.046). CONCLUSION: This project demonstrates that a multifaceted approach targeting modifiable risk factors can reduce incidence of postoperative AKI in T&O patients, which may lead to reduced length of hospital stay and postoperative mortality.

Towards Personalized Management of Ovarian Cancer.

Despite advances in surgery and chemotherapy, the overall outcomes for patients with advanced ovarian cancer remain poor. Although initial response rates to platinum-based chemotherapy is about 60-80%, most patients will have recurrence and succumb to the disease. However, a DNA repair-directed precision medicine strategy has recently generated real hope in improving survival. The clinical development of PARP inhibitors has transformed lives for many patients with BRCA germline-deficient and/or platinum-sensitive epithelial ovarian cancers. Antiangiogenic agents and intraperitoneal chemotherapy approaches may also improve outcomes in patients. Moreover, evolving immunotherapeutic opportunities could also positively impact patient outcomes. Here we review the current clinical state of PARP inhibitors and other clinically viable targeted approaches in ovarian cancer.

Evolving DNA repair synthetic lethality targets in cancer.

DNA damage signaling response and repair (DDR) is a critical defense mechanism against genomic instability. Impaired DNA repair capacity is an important risk factor for cancer development. On the other hand, up-regulation of DDR mechanisms is a feature of cancer chemotherapy and radiotherapy resistance. Advances in our understanding of DDR and its complex role in cancer has led to several translational DNA repair-targeted investigations culminating in clinically viable precision oncology strategy using poly(ADP-ribose) polymerase (PARP) inhibitors in breast, ovarian, pancreatic, and prostate cancers. While PARP directed synthetic lethality has improved outcomes for many patients, the lack of sustained clinical response and the development of resistance pose significant clinical challenges. Therefore, the search for additional DDR-directed drug targets and novel synthetic lethality approaches is highly desirable and is an area of intense preclinical and clinical investigation. Here, we provide an overview of the mammalian DNA repair pathways and then focus on current state of PARP inhibitors (PARPi) and other emerging DNA repair inhibitors for synthetic lethality in cancer.

An assessment of the impact of formal preparation activities on performance in the University Clinical Aptitude Test (UCAT): a national study.

BACKGROUND: Previous studies have shown performance in the University Clinical Aptitude Test (UCAT) to be associated with measures of candidate socio-economic advantage such as parental occupation and type of school attended. It is possible that access to preparation support and materials may in part explain these associations. In this paper we determine whether use of formal preparation resources is associated with higher UCAT scores and whether differences in use of preparation resources exist between socio-demographic groups. METHODS: After completing the 2017 UCAT UK school-leaver candidates (n = 14,332) were asked to answer a questionnaire regarding their use of official UCAT and commercial resources, school-based support, and time spent preparing. Multiple linear and logistic regression models were used to evaluate the associations between preparedness, demographic characteristics and UCAT performance. RESULTS: Five thousand, four hundred thirty-nine (38%) candidates responded to the questionnaire. Use of freely available UCAT official practice tests, paid commercial materials, attendance at school-based preparation courses and spending more time preparing were significantly associated with higher UCAT scores. Candidates who were from less deprived backgrounds and attending independent or grammar schools were significantly more likely to use paid commercial materials and spend longer preparing. CONCLUSIONS: Reported use of preparation resources varies between candidates from different socio-demographic backgrounds and is associated independently with performance in the UCAT. Increasing the availability of freely available resources may mitigate some of these differences.

Does Patellar Resurfacing Matter? Midterm Follow-Up of MRK Total Knee Replacement.

BACKGROUND: Many designs of TKR have been developed to optimize the kinematics and improve satisfaction, including the 'medial rotating' philosophy. The purpose of this study is to report the mid-term clinical outcome of MRK knees and evaluate whether resurfacing the patella makes any difference in outcome. METHODS: A retrospective analysis was done of 104 MRK total knee replacement done between 2008 and 2017. Patients were called for a review for evaluation of OKS, Baldini and Feller scores. Demographics of the patients, clinical outcome, complications were assessed. RESULTS: 62 had patellar resurfacing. Mean follow-up was 74.45 months in non- resurfaced and 54.93 months in resurfaced group. Mean flexion range in both groups at final follow-up was 101.45. Median OKS at follow-up was 36 (12-47) in non-resurfaced and 37 (9-48) in resurfaced group. Patella scores were better in resurfaced group-Baldini score median (range) was 90 (25-100) in non-resurfaced v/s 100 (30-100) in resurfaced, Feller score median (range) was 25 (12-30) in non-resurfaced v/s 28 (10-30) (p 0.042) in resurfaced. The patellofemoral component of the OKS (Q5 + Q7 + Q12) median showed an improvement from 3 (1-11) to 6.5 (3-11) in non-resurfaced and from 3 (0-12) to 8 (2-12) (p 0.039) in resurfaced group. There were five complications overall (4.8%). CONCLUSION: These results show a satisfactory outcome at mid-term follow-up. We found a statistically significant difference in Feller score and in the patellofemoral component of OKS between the groups of MRK knee suggesting specific benefits of patellar resurfacing with this implant.