A Novel Cooling Device for Kidney Transplant Surgery.

Background: Prolonged warm ischemia time (WIT) in kidney transplantation is associated with numerous adverse outcomes including delayed graft function and decreased patient and graft survival. Circumventing WIT lies in maintaining renal hypothermia and efficiently performing the vascular anastomosis during this portion of the procedure. Although numerous methods of intra-operative renal cooling have been proposed, most suffer from practical limitations, and none have been widely adopted. Herein we describe a novel device specifically designed to maintain renal hypothermia during kidney transplant surgery.Methods: Aluminum tubing was organized in a serpentine pattern to create a malleable, form-fitting cooling jacket to manipulate renal allografts during transplant surgery. Adult porcine kidneys were used to test the device with 4°C saline as coolant. Kidneys were placed at 24°C; surface and core temperatures were monitored using implanted thermocouples. Anastomosis of porcine kidney vessels to GORE-TEX® vascular grafts in an ex-vivo operative field was performed to assess the functionality of the device.Results: The device maintained surface and core graft temperatures of ≤5°C after 60 minutes of WIT. Furthermore, the device provided hands-free retraction and support for the allograft. We found that ex-vivo anastomosis testing was enhanced by the presence of the cooling jacket.Conclusions: This proof-of-concept study demonstrated that our novel device is a practical tool for renal transplantation and can maintain sufficiently cool graft temperatures to mitigate WIT in an ex-vivo setting. This device is the first of its kind and has the potential to improve kidney transplant outcomes by eliminating WIT during graft implantation.

Traditional Machine Learning Methods versus Deep Learning for Meningioma Classification, Grading, Outcome Prediction, and Segmentation: A Systematic Review and Meta-Analysis.

BACKGROUND: Meningiomas are common intracranial tumors. Machine learning (ML) algorithms are emerging to improve accuracy in 4 primary domains: classification, grading, outcome prediction, and segmentation. Such algorithms include both traditional approaches that rely on hand-crafted features and deep learning (DL) techniques that utilize automatic feature extraction. The aim of this study was to evaluate the performance of published traditional ML versus DL algorithms in classification, grading, outcome prediction, and segmentation of meningiomas. METHODS: A systematic review and meta-analysis were conducted. Major databases were searched through September 2021 for publications evaluating traditional ML versus DL models on meningioma management. Performance measures including pooled sensitivity, specificity, F1-score, area under the receiver-operating characteristic curve, positive and negative likelihood ratios (LR+, LR-) along with their respective 95% confidence intervals (95% CIs) were derived using random-effects models. RESULTS: Five hundred thirty-four records were screened, and 43 articles were included, regarding classification (3 articles), grading (29), outcome prediction (7), and segmentation (6) of meningiomas. Of the 29 studies that reported on grading, 10 could be meta-analyzed with 2 DL models (sensitivity 0.89, 95% CI: 0.74-0.96; specificity 0.91, 95% CI: 0.45-0.99; LR+ 10.1, 95% CI: 1.33-137; LR- 0.12, 95% CI: 0.04-0.59) and 8 traditional ML (sensitivity 0.74, 95% CI: 0.62-0.83; specificity 0.93, 95% CI: 0.79-0.98; LR+ 10.5, 95% CI: 2.91-39.5; and LR- 0.28, 95% CI: 0.17-0.49). The insufficient performance metrics reported precluded further statistical analysis of other performance metrics. CONCLUSIONS: ML on meningiomas is mostly carried out with traditional methods. For meningioma grading, traditional ML methods generally had a higher LR+, while DL models a lower LR-.

Single Cell Transcriptomic Analysis in a Mouse Model of Barth Syndrome Reveals Cell-Specific Alterations in Gene Expression and Intercellular Communication.

Barth Syndrome, a rare X-linked disorder affecting 1:300,000 live births, results from defects in Tafazzin, an acyltransferase that remodels cardiolipin and is essential for mitochondrial respiration. Barth Syndrome patients develop cardiomyopathy, muscular hypotonia and cyclic neutropenia during childhood, rarely surviving to middle age. At present, no effective therapy exists, and downstream transcriptional effects of Tafazzin dysfunction are incompletely understood. To identify novel, cell-specific, pathological pathways that mediate heart dysfunction, we performed single-nucleus RNA-sequencing (snRNA-seq) on wild-type (WT) and Tafazzin-knockout (Taz-KO) mouse hearts. We determined differentially expressed genes (DEGs) and inferred predicted cell-cell communication networks from these data. Surprisingly, DEGs were distributed heterogeneously across the cell types, with fibroblasts, cardiomyocytes, endothelial cells, macrophages, adipocytes and pericytes exhibiting the greatest number of DEGs between genotypes. One differentially expressed gene was detected for the lymphatic endothelial and mesothelial cell types, while no significant DEGs were found in the lymphocytes. A Gene Ontology (GO) analysis of these DEGs showed cell-specific effects on biological processes such as fatty acid metabolism in adipocytes and cardiomyocytes, increased translation in cardiomyocytes, endothelial cells and fibroblasts, in addition to other cell-specific processes. Analysis of ligand-receptor pair expression, to infer intercellular communication patterns, revealed the strongest dysregulated communication involved adipocytes and cardiomyocytes. For the knockout hearts, there was a strong loss of ligand-receptor pair expression involving adipocytes, and cardiomyocyte expression of ligand-receptor pairs underwent reorganization. These findings suggest that adipocyte and cardiomyocyte mitochondria may be most sensitive to mitochondrial Tafazzin deficiency and that rescuing adipocyte mitochondrial dysfunction, in addition to cardiomyocyte mitochondrial dysfunction, may provide therapeutic benefit in Barth Syndrome patients.

Longitudinal study evaluating post-ICU syndrome differences between acute care surgery and trauma SICU survivors.

BACKGROUND: Post-intensive care unit (ICU) syndrome (PICS) occurs at an exorbitant rate in surgical ICU (SICU) survivors. It remains unknown if critical illness due to trauma versus acute care surgery (ACS) may represent different pathophysiologic entities. In this longitudinal study, we determined if admission criteria in a cohort of trauma and ACS patients were associated with differences in the occurrence of PICS. METHODS: Patients were 18 years or older, admitted to a Level I trauma center to the trauma or ACS services, remained in the SICU for ≥72 hours, and were seen in an ICU Recovery Center at 2 weeks, 12 weeks, and 24 weeks after hospital discharge. Post-ICU syndrome sequelae were diagnosed by dedicated specialist staffing using clinical criteria and screening questionnaires. The PICS symptoms were distilled into physical, cognitive, and psychiatric categories. Preadmission histories, hospital courses, and recovery data were collected via retrospective chart review. RESULTS: One hundred twenty-six patients were included: 74 (57.3%) trauma patients and 55 (42.6%) ACS patients. Prehospital psychosocial histories were similar between groups. Acute care surgery patients had a significantly longer hospital course, higher APACHE II and III scores, were intubated for longer, and had higher rates of sepsis, acute renal failure, open abdomen, and hospital readmissions. At the 2-week follow-up visit, ACS patients had higher rates of PICS sequelae (ACS, 97.8% vs. trauma 85.3%; p = 0.03), particularly in the physical (ACS, 95.6% vs. trauma 82.0%, p = 0.04), and psychiatric domains (ACS, 55.6% vs. trauma 35.0%, p = 0.04). At the 12-week and 24-week visits, rates of PICS symptoms were comparable between groups. CONCLUSION: The occurrence of PICS is extraordinarily high in both trauma and ACS SICU survivors. Despite entering the SICU with similar psychosocial histories, the two cohorts have different pathophysiologic experiences, which are associated with a higher rate of impairment in the ACS patients during early follow-up. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

High Levels of Satisfaction and Adequate Patient-Reported Outcomes After Operative Reconstruction of Multiligament Knee Injury With Allograft Among Patients Aged 40 Years and Older.

Purpose: To describe injury characteristics and patient-reported outcomes (PROs) among patients aged 40 years and older who underwent allograft reconstruction for multiligament knee injury (MLKI). Methods: Records of patients aged 40 years and older who underwent allograft multiligament knee reconstruction at a single institution between 2007 and 2017 with a minimum of 2 years of follow-up were retrospectively reviewed. Demographic information, concomitant injuries, patient satisfaction, and PROs including International Knee Documentation Committee and Marx activity scores were obtained. Results: Twelve patients were included with a minimum follow-up time of 2.3 years (mean, 6.1; range, 2.3-10.1 years) and a mean age at surgery of 49.8 years. Seven patients were male, and the most common mechanism of injury was sport-related. The most frequently reconstructed MLKIs were anterior cruciate ligament and medial collateral ligament (4), anterior cruciate ligament and posterolateral corner (2), and posterior cruciate ligament and posterolateral corner (2). The majority of patients reported satisfaction with their treatment (11). Median International Knee Documentation Committee and Marx scores were 73 (interquartile range, 45.5-88.0) and 3 (interquartile range 0-5), respectively. Conclusions: Patients aged 40 years and older can expect a high level of satisfaction and adequate PROs at 2-years follow-up after operative reconstruction for a MLKI with allograft. This demonstrates that allograft reconstruction for a MLKI in older patients may have clinical utility. Level of Evidence: IV, therapeutic case series.

Revision Soft-Tissue Allograft Anterior Cruciate Ligament Reconstruction Is Associated With Lower Patient-Reported Outcomes Compared With Primary Anterior Cruciate Ligament Reconstruction in Patients Aged 40 and Older.

PURPOSE: To evaluate patient-reported outcomes (PROs) and graft failure rates in revision allograft anterior cruciate ligament reconstruction (ACLR) in patients aged 40 and older and compare them with primary ACLRs. METHODS: Patients aged 40 and older who underwent arthroscopic soft-tissue allograft ACLR between 2005 and 2016 with a minimum 2-year follow-up were retrospectively reviewed. Patients were grouped based on revision versus primary ACLR. The rate of achieving an International Knee Documentation Committee (IKDC) patient acceptable symptom state (PASS) score was recorded. Patient satisfaction, PROs, and graft failure were compared between groups using the χ2 test, Fisher exact test, and Mann-Whitney U test. RESULTS: We identified 32 patients who underwent revision ACLR and 201 patients who underwent primary ACLR aged 40 and older who met inclusion criteria with a mean follow-up of 6.2 and 6.9 years, respectively (P = .042). There was a lower rate of concomitant meniscal repair in the primary ACLR group (6% vs 21.9%, P = .007) There were no other differences in chondral injuries, mechanism of injury, or meniscal injuries between groups. The median IKDC score was greater in the primary ACLR group as compared with the revision ACLR group (83.9 vs 70.6, P < .001). Patients who underwent revision ACLR were less likely to achieve the IKDC PASS threshold (82.5% vs 56.3%, P = .001) and were less likely to report satisfaction as compared with patients who underwent primary ACLR (90.5% vs 78.1%, P =.038). No difference in graft failure rates was identified between groups (8% vs 15.6%, P = .180). CONCLUSIONS: Revision allograft ACLR in patients aged 40 and older was associated with lower PROs compared with primary ACLR. Patients who underwent revision ACLR failed to meet the IKDC PASS threshold more often and were dissatisfied with procedure results more than twice as often as patients that underwent primary ACLR. LEVEL OF EVIDENCE: III, retrospective cohort study.

Case report: Asymptomatic renal arteriovenous fistula requiring endovascular embolization in a living donor transplanted kidney more than 15-years after last protocol biopsy.

Here we present the case of an HLA-identical living-donor kidney transplant recipient, who was incidentally found to have a large complex renal arteriovenous fistula (RAVF) in their transplanted kidney that had been present for nearly 6 years but was previously misinterpreted as being part of a collection of cysts. This patient had undergone 7 protocol biopsies of the transplanted kidney, the last of which had been performed approximately 16 years prior, representing the longest interval between most recent biopsy renal allograft to RAVF diagnosis in the literature date. This report reviews the etiology and principles of management for RAVF.

Spontaneous, atraumatic hydrocele rupture: A case report.

There is little information in the literature on the management and prognosis of ruptured hydroceles. We present a case report of spontaneous, atraumatic left hydrocele rupture in a 64-year-old male. His hydrocele was initially diagnosed as non-complex and appeared to have ruptured spontaneously three years after initial onset. On follow-up in clinic, mild re-accumulation of fluid was observed, and no pain was reported by the patient. Post-rupture fluid re-accumulation was minimal in our patient but there is potential for significant fluid re-accumulation based on other reports of ruptured hydroceles.

Developing an Immersive Virtual Reality Training System for Novel Pediatric Power Wheelchair Users: Protocol for a Feasibility Study.

BACKGROUND: Power wheelchairs can empower children with physical limitations to gain independence in their everyday lives; however, traditional methods of power wheelchair training are often limited by poor accessibility and safety concerns. Immersive virtual reality technology (IVRT) uses advanced display technology to place users in a fully immersive web-based environment that can support real-time skills training, often requiring less resources and fewer safety concerns than real-world methods. IVRT interventions have shown to be a feasible training option among adult power wheelchair users; however, there is still a need to understand the technical and clinical feasibility of developing an IVRT power wheelchair training tool for the pediatric population. OBJECTIVE: This proposed study aims to use expert feedback and an iterative design process to develop an IVRT training intervention for pediatric power wheelchair skill development. METHODS: This 3-phase feasibility study will be conducted within the assistive technology unit of a public pediatric hospital. Separate participant groups will be recruited for each phase, consisting of approximately 10 to 15 clinicians (phase 1), 10 pediatric power wheelchair users (phase 2), and 15 to 20 additional pediatric power wheelchair users (phase 3). Phase 1 will be conducted to gather feedback on the baseline IVRT training intervention. Clinicians will test the intervention and assess its usability and acceptability using qualitative and quantitative methods. Phase 1 participants will also be invited back for a subsequent session to reassess a revised version of the training intervention that has been updated based on their previous feedback. Phase 2 and phase 3 will also use mixed methods to gather feedback on the usability, acceptability, and user experience of the IVRT training intervention from current pediatric power wheelchair users. In addition, phase 3 participants will perform a skills transfer assessment to compare power mobility skill performance between the virtual reality and real-life environments. Data gathered in phase 2 will be used to further refine the IVRT intervention, whereas phase 3 data will be used to statistically evaluate the final version. RESULTS: This study was approved by the Izaak Walton Killam Health Centre research ethics board in August 2021. Phase 1 testing began in February 2022. The entire study is expected to be completed by 2023. CONCLUSIONS: The results of this study will be used to create an IVRT training intervention for pediatric power wheelchair skill development through an iterative and collaborative design process. Results may also assist in directing future studies in this area. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39140.

Effect of Tranexamic Acid on Bleeding Outcomes After Percutaneous Nephrolithotomy: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Purpose: We performed a systematic review and meta-analysis of the literature to evaluate the efficacy of the routine use of tranexamic acid (TXA) during percutaneous nephrolithotomy (PCNL). Methods: This systematic review was conducted following the updated reporting guidelines from PRISMA 2020. Results: In total, 275 titles and abstracts were reviewed, of which 20 were screened to be eligible for full text review. Of these 20 articles, 11 were selected for inclusion after full article evaluations. Seven of these 11 studies were seen as having a low risk of bias with a Jadad score of ≥3. These studies were included for data extraction. Once data were extracted, 964 patients were included. The primary outcome, blood transfusion rate, showed significant reduction with a ratio for transfusion rate of 0.34 [95% confidence interval (CI) (0.19 to 0.61), z = 3.61, p = 0.0003]. Mean hemoglobin (Hgb) drop and operative time were both shown to be reduced with the use of TXA. The mean difference for Hgb drop was -0.86 [95% CI (-1.26 to -0.46), z = 4.23, p < 0.0001]. Reduction in operative time showed a mean difference of -8.45 minutes [95% CI (-15.04 to -1.86), z = 2.51, p = 0.01]. Stone clearance was not shown to differ significantly between experimental and control groups, with a risk ratio of 1.28 [95% CI (0.89 to 1.84), z = 1.31, p = 0.19]. Conclusions: This meta-analysis revealed that the routine use of TXA at time of PCNL reduces the rates of blood transfusion, mean Hgb drop, and operative time. With the low cost of TXA and strong safety profile, stronger consideration should be given to the routine use of TXA during PCNL by endoscopic surgeons.

Arthroscopic Anatomic Glenoid Repair Using Distal Tibial Allograft and an Inferior-to-Superior Capsular Shift.

Traumatic anterior dislocation of the shoulder accounts for the vast majority of shoulder dislocations. Recurrence following initial traumatic dislocation is common, and the risk is increased by the presence of both bony and soft-tissue damage. Arthroscopic procedures have been described to address each of these etiologies individually but have not provided a technique to address bony and soft tissue pathology concurrently. This paper describes an all-arthroscopic, anatomic glenoid repair using distal tibial allograft with an inferior-to-superior capsular shift, addressing significant glenoid bone loss and capsular laxity with a single operation.

Experiences from the first 10 years of a perinatal palliative care program: A retrospective chart review.

BACKGROUND: Perinatal palliative care is a relatively new component of paediatric palliative care which supports families who are expecting the birth of a child with a life-limiting condition. This study seeks to understand the characteristics of the infants and families referred for perinatal palliative care and the context for referrals in terms of diagnoses, referral characteristics, interventions, and outcomes. METHODS: A retrospective chart review of infants with prenatally diagnosed life-limiting conditions that were referred for perinatal palliative care. RESULTS: Eighty-five referrals were made for perinatal palliative care during the 10-year period, of which, 84 chose to continue with the service. Average gestational age at diagnosis was 23 weeks, and the mean time between diagnosis and referral to palliative care was 7 weeks. Stillbirths were common, occurring in 29% cases. Of livebirths, 59% of the infants survived for 2 days, and 80% died within 30 days. The most commonly referred conditions were trisomy 13 or 18 (24%), severe central nervous system malformations (20%), and severe congenital cardiac disease (16%). Referrals were most often made by neonatologists (39%), and maternal-fetal medicine specialists (36%). DISCUSSION: Our study confirms previously observed characteristics of diagnosis, referrals, and outcomes, while providing the most detailed account of lifespans for particular diagnoses to date. Our findings validate the need for perinatal palliative care, as 99% of those referred continued with the service. Future research should adopt a prospective approach to identify critical factors affecting decision making of families and physicians in the wake of a life-limiting diagnosis.

Delivering Hospital-Based Pediatric Palliative Care: The Symptoms, Interventions, and Outcomes for Children With Cancer in Bangladesh.

PURPOSE: The majority of pediatric cancer deaths occur in low- and middle-income countries (LMICs). Pediatric palliative care (PPC) focuses on relieving physical, psychosocial, and spiritual suffering throughout the continuum of cancer care and is considered integral to cancer care for children in all settings. There is limited evidence from LMICs about the characteristics, symptoms, and outcomes of children with cancer who receive PPC, which is needed to define the global need and guide the development of these services. METHODS: This retrospective review of clinical records of children who received PPC was conducted during a pilot project (January 2014-August 2015) that implemented a PPC team at a tertiary hospital in Dhaka, Bangladesh. Clinical data on diagnosis, symptoms, treatment status, deaths, and key palliative care interventions were collected and analyzed using descriptive statistics. RESULTS: There were 200 children who received PPC during the pilot project. The most common diagnoses were acute lymphoblastic leukemia (62%) and acute myeloid leukemia (11%). Psychosocial support for children (n = 305; 53%) and management of physical symptoms (n = 181; 31%) were the most common types of interventions provided. The most frequently recorded symptoms were pain (n = 60; 30%), skin wounds (n = 16; 8%), and weakness (n = 9; 5%). The most common medications prescribed were morphine (n = 32) and paracetamol (n = 21). CONCLUSION: A hospital-based PPC service addresses pain and symptom concerns as well as psychosocial needs for children with cancer and their families in a setting where resources are limited. Health care facilities should incorporate palliative care into the care of children with cancer to address the needs of children and their families.

Illness-related suffering and need for palliative care in Rohingya refugees and caregivers in Bangladesh: A cross-sectional study.

BACKGROUND: Despite recognition that palliative care is an essential component of any humanitarian response, serious illness-related suffering continues to be pervasive in these settings. There is very limited evidence about the need for palliative care and symptom relief to guide the implementation of programs to alleviate the burden of serious illness-related suffering in these settings. A basic package of essential medications and supplies can provide pain relief and palliative care; however, the practical availability of these items has not been assessed. This study aimed to describe the illness-related suffering and need for palliative care in Rohingya refugees and caregivers in Bangladesh. METHODS AND FINDINGS: Between November 20 and 24, 2017, we conducted a cross-sectional study of individuals with serious health problems (n = 156, 53% male) and caregivers (n = 155, 69% female) living in Rohingya refugee camps in Bangladesh, using convenience sampling to recruit participants at the community level (i.e., going house to house to identify eligible individuals). The serious health problems, recent healthcare experiences, need for medications and medical supplies, and basic needs of participants were explored through interviews with trained Rohingya community members, using an interview guide that had been piloted with Rohingya individuals to ensure it reflected the specificities of their refugee experience and culture. The most common diagnoses were significant physical disabilities (n = 100, 64.1%), treatment-resistant tuberculosis (TB) (n = 32, 20.5%), cancer (n = 15, 9.6%), and HIV infection (n = 3, 1.9%). Many individuals with serious health problems were experiencing significant pain (62%, n = 96), and pain treatments were largely ineffective (70%, n = 58). The average age was 44.8 years (range 2-100 years) for those with serious health problems and 34.9 years (range 8-75 years) for caregivers. Caregivers reported providing an average of 13.8 hours of care per day. Sleep difficulties (87.1%, n = 108), lack of appetite (58.1%, n = 72), and lack of pleasure in life (53.2%, n = 66) were the most commonly reported problems related to the caregiving role. The main limitations of this study were the use of convenience sampling and closed-ended interview questioning. CONCLUSIONS: In this study we found that many individuals with serious health problems experienced significant physical, emotional, and social suffering due to a lack of access to pain and symptom relief and other essential components of palliative care. Humanitarian responses should develop and incorporate palliative care and symptom relief strategies that address the needs of all people with serious illness-related suffering and their caregivers.

aTEMPO: Pathway-Specific Temporal Anomalies for Precision Therapeutics.

Dynamic processes are inherently important in disease, and identifying disease-related disruptions of normal dynamic processes can provide information about individual patients. We have previously characterized individuals' disease states via pathway-based anomalies in expression data, and we have identified disease-correlated disruption of predictable dynamic patterns by modeling a virtual time series in static data. Here we combine the two approaches, using an anomaly detection model and virtual time series to identify anomalous temporal processes in specific disease states. We demonstrate that this approach can informatively characterize individual patients, suggesting personalized therapeutic approaches.

The Psychosocial and Spiritual Experiences of Patients with Advanced Incurable Illness in Bangladesh: A Cross-Sectional Observational Study.

CONTEXT: The psychosocial and spiritual needs of individuals with life-limiting conditions in low- or middle-income countries have not been well described. Understanding these needs is important to providing holistic palliative care. AIM: This study aims to better understand the psychosocial and spiritual needs and supports of patients with advanced, incurable illness in Bangladesh. SUBJECTS AND METHODS: Individuals with advanced incurable illnesses (advanced cancer and HIV/AIDS) from a wide geographical distribution across Bangladesh were interviewed about their health status, emotional and spiritual experiences with their illness, coping and support systems, and greatest needs and fears. RESULTS: We interviewed 221 individuals with incurable cancer (82%) or HIV/AIDS (18%). Self-reported health status was poor or very poor for 48%, and 44% reported feeling unhappy all of the time. The majority (61%) rated their current level of unhappiness as 10/10. Spouses (50%), children (15%), and parents (13%) were the most common caregivers. Money and medical care were equally the most common needs (46%). Participants' greatest fears were for the future of their children (38%), being in pain (29%), and dying (28%). CONCLUSIONS: There is a significant burden of psychosocial and spiritual concerns among patients with advanced incurable illness in Bangladesh, with sadness being very frequent and of high intensity. Family and friends provide significant emotional and practical support to patients who are seriously ill, but very few patients access any professional support for these concerns.