Pancreatic transplantation at the University of Pittsburgh.

Campath-1H preconditioning with tacrolimus monotherapy is an effective immunosuppressive regimen for pancreas transplantation, with acceptable patient and graft survival rates early after transplantation. Rejection rates are low under this protocol if the tacrolimus level is kept consistently >10 ng/ml. This immunosuppressive protocol, combined with recent technical refinements, has resulted in lower rates of thrombosis and overall complications. Pancreatic transplantation en-bloc with visceral grafts has the following unique features: Diabetes is a rare indication, and HLA matching is not required. The gland is immunologically protected by the simultaneously transplanted visceral organs. Disease gravity, surgical complexity and gut alloimmunity influence the overall pancreatic allograft survival. The current UNOS listing criteria and data registry should be modified for obvious logistic and scientific reasons

Historical and future trends in emergency pituitary referrals: a machine learning analysis

Purpose: Acute pituitary referrals to neurosurgical services frequently necessitate emergency care. Yet, a detailed characterisation of pituitary emergency referral patterns, including how they may change prospectively is lacking. This study aims to evaluate historical and current pituitary referral patterns and utilise state-of-the-art machine learning tools to predict future service use. Methods: A data-driven analysis was performed using all available electronic neurosurgical referrals (2014–2021) to the busiest U.K. pituitary centre. Pituitary referrals were characterised and volumes were predicted using an auto-regressive moving average model with a preceding seasonal and trend decomposition using Loess step (STL-ARIMA), compared against a Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM) algorithm, Prophet and two standard baseline forecasting models. Median absolute, and median percentage error scoring metrics with cross-validation were employed to evaluate algorithm performance. Results: 462 of 36,224 emergency referrals were included (referring centres = 48; mean patient age = 56.7 years, female:male = 0.49:0.51). Emergency medicine and endocrinology accounted for the majority of referrals (67%). The most common presentations were headache (47%) and visual field deficits (32%). Lesions mainly comprised tumours or haemorrhage (85%) and involved the pituitary gland or fossa (70%). The STL-ARIMA pipeline outperformed CNN-LSTM, Prophet and baseline algorithms across scoring metrics, with standard accuracy being achieved for yearly predictions. Referral volumes significantly increased from the start of data collection with future projected increases (p < 0.001) and did not significantly reduce during the COVID-19 pandemic. Conclusion: This work is the first to employ large-scale data and machine learning to describe and predict acute pituitary referral volumes, estimate future service demands, explore the impact of system stressors (e.g. COVID pandemic), and highlight areas for service improvement

Outcomes of preexisting diabetes mellitus in breast, colorectal, and prostate cancer.

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.PURPOSE: Preexisting diabetes is associated with increased morbidity and mortality in cancer. We examined the impact of incident cancer on the long-term outcomes of diabetes. METHODS: Using the United Kingdom Clinical Practice Research Datalink, we identified three cohorts of diabetes patients subsequently diagnosed with breast, colorectal, or prostate cancer, each matched to diabetic noncancer controls. Patients were required to have survived at least 1 year after cancer diagnosis (cases) or a matched index date (controls), and were followed up to 10 years for incident microvascular and macrovascular complications and mortality. Multivariate competing risks regression analyses were used to compare outcomes between cancer patients and controls. RESULTS: Overall, there were 3382 cancer patients and 11,135 controls with 59,431 person-years of follow-up. In adjusted analyses, there were no statistically significant (p ≤ 0.05) differences in diabetes complication rates between cancer patients and their controls in any of the three cancer cohorts. Combined, cancer patients were less likely (adjusted hazard ratio [HR] 0.88; 95% CI = 0.79-0.98) to develop retinopathy. Cancer patients were more likely to die of any cause (including cancer), but prostate cancer patients were less likely to die of causes associated with diabetes (HR 0.61; 95% CI = 0.43-0.88). CONCLUSIONS AND IMPLICATIONS: There is no evidence that incident cancer had an adverse impact on the long-term outcomes of preexisting diabetes. IMPLICATIONS FOR CANCER SURVIVORS: These findings are important for cancer survivors with preexisting diabetes because they suggest that substantial improvements in the relative survival of several of the most common types of cancer are not undermined by excess diabetes morbidity and mortality.This study was funded by the Population Research Committee, Cancer Research UK. Quality and Outcomes of Care for Chronic Conditions in Older Patients Diagnosed with Breast, Colorectal, or Prostate Cancer Compared to Non-Cancer Controls: An Observational Study Using the Clinical Practice Research Datalink (CPRD). Reference # 16609. 1 July 2013–29 February, 2016. In addition, Dr. Keating is supported by K24CA181510 from the US National Cancer Institute

Outcomes of preexisting diabetes mellitus in breast, colorectal, and prostate cancer.

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.PURPOSE: Preexisting diabetes is associated with increased morbidity and mortality in cancer. We examined the impact of incident cancer on the long-term outcomes of diabetes. METHODS: Using the United Kingdom Clinical Practice Research Datalink, we identified three cohorts of diabetes patients subsequently diagnosed with breast, colorectal, or prostate cancer, each matched to diabetic noncancer controls. Patients were required to have survived at least 1 year after cancer diagnosis (cases) or a matched index date (controls), and were followed up to 10 years for incident microvascular and macrovascular complications and mortality. Multivariate competing risks regression analyses were used to compare outcomes between cancer patients and controls. RESULTS: Overall, there were 3382 cancer patients and 11,135 controls with 59,431 person-years of follow-up. In adjusted analyses, there were no statistically significant (p ≤ 0.05) differences in diabetes complication rates between cancer patients and their controls in any of the three cancer cohorts. Combined, cancer patients were less likely (adjusted hazard ratio [HR] 0.88; 95% CI = 0.79-0.98) to develop retinopathy. Cancer patients were more likely to die of any cause (including cancer), but prostate cancer patients were less likely to die of causes associated with diabetes (HR 0.61; 95% CI = 0.43-0.88). CONCLUSIONS AND IMPLICATIONS: There is no evidence that incident cancer had an adverse impact on the long-term outcomes of preexisting diabetes. IMPLICATIONS FOR CANCER SURVIVORS: These findings are important for cancer survivors with preexisting diabetes because they suggest that substantial improvements in the relative survival of several of the most common types of cancer are not undermined by excess diabetes morbidity and mortality.This study was funded by the Population Research Committee, Cancer Research UK. Quality and Outcomes of Care for Chronic Conditions in Older Patients Diagnosed with Breast, Colorectal, or Prostate Cancer Compared to Non-Cancer Controls: An Observational Study Using the Clinical Practice Research Datalink (CPRD). Reference # 16609. 1 July 2013–29 February, 2016. In addition, Dr. Keating is supported by K24CA181510 from the US National Cancer Institute

Quality of diabetes care in breast, colorectal, and prostate cancer

This is the final version. Available on open access from Springer via the DOI in this recordPURPOSE: Overlooking other medical conditions during cancer treatment and follow-up could result in excess morbidity and mortality, thereby undermining gains associated with early detection and improved treatment of cancer. We compared the quality of care for diabetes patients subsequently diagnosed with breast, colorectal, or prostate cancer to matched, diabetic non-cancer controls. METHODS: Longitudinal cohort study using primary care records from the Clinical Practice Research Datalink, United Kingdom. Patients with pre-existing diabetes were followed for up to 5 years after cancer diagnosis, or after an assigned index date (non-cancer controls). Quality of diabetes care was estimated based on Quality and Outcomes Framework indicators. Mixed effects logistic regression analyses were used to compare the unadjusted and adjusted odds of meeting quality measures between cancer patients and controls, overall and stratified by type of cancer. RESULTS: 3382 cancer patients and 11,135 controls contributed 44,507 person-years of follow-up. In adjusted analyses, cancer patients were less likely to meet five of 14 quality measures, including: total cholesterol ≤ 5 mmol/L (odds ratio [OR] = 0.82; 95% confidence interval [CI], 0.75-0.90); glycosylated hemoglobin ≤ 59 mmol/mol (adjusted OR = 0.77; 95% CI, 0.70-0.85); and albumin creatinine ratio testing (adjusted OR = 0.83; 95% CI, 0.75-0.91). However, cancer patients were as likely as their matched controls to meet quality measures for other diabetes services, including retinal screening, foot examination, and dietary review. CONCLUSIONS: Although in the short-term, cancer patients were less likely to achieve target thresholds for cholesterol and HbA1c, they continued to receive high-quality diabetes primary care throughout 5 years post diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: These findings are important for cancer survivors with pre-existing diabetes because they indicate that high-quality diabetes care is maintained throughout the continuum of cancer diagnosis, treatment, and follow-up.This study was funded by the Population Research Committee, Cancer Research UK. Quality and Outcomes of Care for Chronic Conditions in Older Patients Diagnosed with Breast, Colorectal, or Prostate Cancer Compared to Non-Cancer Controls: An Observational Study Using the Clinical Practice Research Datalink (CPRD). Reference # 16609. 1 July 2013–29 February, 2016. In addition, Dr. Keating is supported by K24CA181510 from the US National Cancer Institute

Introducing a gender-sensitive approach to pre-trial assessment and probation: Evaluation of an innovation in Kenya

This paper evaluates a pioneering project to introduce a gender-sensitive approach to working with women completing probation and community service orders in Kenya. The intervention consisted of context-specific research with women throughout Kenya, leading to adaptations to existing probation tools, followed by pilot implementation of a gender-sensitive approach. The evaluation explores the relevance, effectiveness and sustainability of the intervention and presents opinions of implementing probation officers and sector experts. Findings suggest that the project genuinely broke new ground in terms of research on gender-sensitivity and quality of pre-trial reporting for women. Close adherence to the UN Bangkok Rules means the model and lessons are applicable both domestically and globally

The clinical outcomes of imaging modalities for surgical management Cushing’s disease – A systematic review and meta-analysis

Introduction: Cushing’s disease presents major diagnostic and management challenges. Although numerous preoperative and intraoperative imaging modalities have been deployed, it is unclear whether these investigations have improved surgical outcomes. Our objective was to investigate whether advances in imaging improved outcomes for Cushing’s disease. Methods: Searches of PubMed and EMBASE were conducted. Studies reporting on imaging modalities and clinical outcomes after surgical management of Cushing’s disease were included. Multilevel multivariable meta-regressions identified predictors of outcomes, adjusting for confounders and heterogeneity prior to investigating the effects of imaging. Results: 166 non-controlled single-arm studies were included, comprising 13181 patients over 44 years. The overall remission rate was 77.0% [CI: 74.9%-79.0%]. Cavernous sinus invasion (OR: 0.21 [CI: 0.07-0.66]; p=0.010), radiologically undetectable lesions (OR: 0.50 [CI: 0.37–0.69]; p<0.0001), previous surgery (OR=0.48 [CI: 0.28–0.81]; p=0.008), and lesions ≥10mm (OR: 0.63 [CI: 0.35–1.14]; p=0.12) were associated with lower remission. Less stringent thresholds for remission was associated with higher reported remission (OR: 1.37 [CI: 1.1–1.72]; p=0.007). After adjusting for this heterogeneity, no imaging modality showed significant differences in remission compared to standard preoperative MRI. The overall recurrence rate was 14.5% [CI: 12.1%-17.1%]. Lesion ≥10mm was associated with greater recurrence (OR: 1.83 [CI: 1.13–2.96]; p=0.015), as was greater duration of follow-up (OR: 1.53 (CI: 1.17–2.01); p=0.002). No imaging modality was associated with significant differences in recurrence. Despite significant improvements in detection rates over four decades, there were no significant changes in the reported remission or recurrence rates. Conclusion: A lack of controlled comparative studies makes it difficult to draw definitive conclusions. Within this limitation, the results suggest that despite improvements in radiological detection rates of Cushing’s disease over the last four decades, there were no changes in clinical outcomes. Advances in imaging alone may be insufficient to improve surgical outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020187751

Automated operative workflow analysis of endoscopic pituitary surgery using machine learning: development and preclinical evaluation (IDEAL stage 0)

OBJECTIVE: Surgical workflow analysis involves systematically breaking down operations into key phases and steps. Automatic analysis of this workflow has potential uses for surgical training, preoperative planning, and outcome prediction. Recent advances in machine learning (ML) and computer vision have allowed accurate automated workflow analysis of operative videos. In this Idea, Development, Exploration, Assessment, Long-term study (IDEAL) stage 0 study, the authors sought to use Touch Surgery for the development and validation of an ML-powered analysis of phases and steps in the endoscopic transsphenoidal approach (eTSA) for pituitary adenoma resection, a first for neurosurgery. METHODS: The surgical phases and steps of 50 anonymized eTSA operative videos were labeled by expert surgeons. Forty videos were used to train a combined convolutional and recurrent neural network model by Touch Surgery. Ten videos were used for model evaluation (accuracy, F1 score), comparing the phase and step recognition of surgeons to the automatic detection of the ML model. RESULTS: The longest phase was the sellar phase (median 28 minutes), followed by the nasal phase (median 22 minutes) and the closure phase (median 14 minutes). The longest steps were step 5 (tumor identification and excision, median 17 minutes); step 3 (posterior septectomy and removal of sphenoid septations, median 14 minutes); and step 4 (anterior sellar wall removal, median 10 minutes). There were substantial variations within the recorded procedures in terms of video appearances, step duration, and step order, with only 50% of videos containing all 7 steps performed sequentially in numerical order. Despite this, the model was able to output accurate recognition of surgical phases (91% accuracy, 90% F1 score) and steps (76% accuracy, 75% F1 score). CONCLUSIONS: In this IDEAL stage 0 study, ML techniques have been developed to automatically analyze operative videos of eTSA pituitary surgery. This technology has previously been shown to be acceptable to neurosurgical teams and patients. ML-based surgical workflow analysis has numerous potential uses-such as education (e.g., automatic indexing of contemporary operative videos for teaching), improved operative efficiency (e.g., orchestrating the entire surgical team to a common workflow), and improved patient outcomes (e.g., comparison of surgical techniques or early detection of adverse events). Future directions include the real-time integration of Touch Surgery into the live operative environment as an IDEAL stage 1 (first-in-human) study, and further development of underpinning ML models using larger data sets

Cancer screening and preventative care among long-term cancer survivors in the United Kingdom

BACKGROUND: Long-term cancer survivors in the United Kingdom are mostly followed up in a primary care setting by their general practitioner; however, there is little research on the use of services. This study examines whether cancer survivors receive adequate screening and preventative care in UK primary care. PATIENTS AND METHODS: We identified a cohort of long-term survivors of breast, colorectal and prostate cancer with at least a 5-year survival using the General Practice Research Database, with controls matched for age, gender and practice. We compared adherence with cancer screening and the use of preventative care between cancer survivors and controls. RESULTS: The cancer survivors' cohort consisted of 18 612 breast, 5764 colorectal and 4868 prostate cancer survivors. Most cancer survivors receive cancer screening at the same levels as controls, except for breast cancer survivors who were less likely to receive a mammogram than controls (OR=0.78, 95% CI: 0.66-0.92). Long-term cancer survivors received comparable levels of influenza vaccinations and cholesterol tests, but breast (OR 0.81, 95% CI: 0.74-0.87) and prostate cancer survivors (OR=0.70, 95% CI: 0.57-0.87) were less likely to receive a blood pressure test. All survivors were more likely to receive bone densitometry. CONCLUSION: The provision and uptake of preventive care in a primary care setting in the United Kingdom is comparable between the survivors of three common cancers and those who have not had cancer. However, long-term breast cancer survivors in this cohort were less likely to receive a mammogra