The Commonwealth Fund Survey of Primary Care Physicians Reveals Challenges Experienced by Family Doctors and Emphasizes the Need for Interoperability of Health Information Technologies.

Electronic health information that is easily accessible and shareable among healthcare providers and their patients can provide substantial improvements in Canada's primary care system and population health outcomes. The Commonwealth Fund's (CMWF's) 2022 International Health Policy Survey of Primary Care Physicians (CIHI 2023) highlights the views and experiences of primary care doctors in 10 developed countries, including Canada. The survey covered various topics related to physician workload, the use of information technology and coordination of care. While the COVID-19 pandemic contributed to an increased physician workload that may have impacted the ability to efficiently coordinate care with other healthcare providers, Canadian family doctors did close the gap with other countries as 93% of family doctors are now using electronic medical records (EMRs) in their practices. The CMWF's 2022 survey revealed challenges faced by Canadian family doctors in their practices. However, international comparisons provide opportunities to learn from other countries and build on the implementation of EMRs as part of Canada's shared health priorities.

Surface salt bridges contribute to the extreme thermal stability of an FN3-like domain from a thermophilic bacterium.

This study uses differential scanning calorimetry, X-ray crystallography, and molecular dynamics simulations to investigate the structural basis for the high thermal stability (melting temperature 97.5°C) of a FN3-like protein domain from thermophilic bacteria Thermoanaerobacter tengcongensis (FN3tt). FN3tt adopts a typical FN3 fold with a three-stranded beta sheet packing against a four-stranded beta sheet. We identified three solvent exposed arginine residues (R23, R25, and R72), which stabilize the protein through salt bridge interactions with glutamic acid residues on adjacent strands. Alanine mutation of the three arginine residues reduced melting temperature by up to 22°C. Crystal structures of the wild type (WT) and a thermally destabilized (∆Tm -19.7°C) triple mutant (R23L/R25T/R72I) were found to be nearly identical, suggesting that the destabilization is due to interactions of the arginine residues. Molecular dynamics simulations showed that the salt bridge interactions in the WT were stable and provided a dynamical explanation for the cooperativity observed between R23 and R25 based on calorimetry measurements. In addition, folding free energy changes computed using free energy perturbation molecular dynamics simulations showed high correlation with melting temperature changes. This work is another example of surface salt bridges contributing to the enhanced thermal stability of thermophilic proteins. The molecular dynamics simulation methods employed in this study may be broadly useful for in silico surface charge engineering of proteins.

Motor Vehicle Collision and Acute Kidney Injury in Children.

OBJECTIVE: Our study aimed to determine the prevalence of acute kidney injury (AKI) in pediatric patients who sustained trauma due to motor vehicle collision (MVC) and identify factors associated with its development. METHODS: We retrospectively reviewed the clinical information and laboratory tests of pediatric patients who were admitted because of MVC from January 2014 to April 2021. The occurrence of AKI was our primary outcome, which was defined by the Kidney Disease Improving Global Outcomes criteria. A serum creatine kinase (CK) level of 1000 IU/L or greater was defined as rhabdomyolysis. RESULTS: Sixty-four patients (median age, 9.6 years) were included in the study. Twenty three of the patients (35.9%) developed AKI: stage 1 AKI in 18 (78.3%) and stage 2 AKI in 5 (21.7%) patients. Acute kidney injury patients had higher injury severity scores (no AKI: 5.0; stage 1 AKI: 10.5; stage 2 AKI: 26.0). Rhabdomyolysis was present in 21.1% of the patients and was associated with the overall AKI risk (odds ratio [OR], 7.3; 95% confidence interval [CI], 1.6-32.6) and stage 2 AKI (OR, 15.0; 95% CI, 1.4-163.2). Blood tests from AKI patients showed lower serum bicarbonate and base excess, higher leukocyte and CK levels on admission, and a higher peak CK in the first 72 hours of admission. Intubation in emergency department (OR, 11.1; 95% CI, 1.2-102.1) and surgical interventions (OR, 3.2; 95% CI, 1.0-9.8) were associated with AKI. Acute kidney injury patients required longer stay in pediatric intensive care unit (median 1.0 vs 2.3 days, P < 0.001) and hospital (median 4.1 vs 7.0 days, P = 0.010). CONCLUSIONS: Approximately one third of pediatric patients who sustained trauma from MVC developed AKI. Initial blood results, including higher CK and leukocyte count, and lower bicarbonate and base excess, were associated with the development of AKI. Rhabdomyolysis occurred in approximately one fifth of the patients and was significantly associated with AKI.

Acute kidney injury in pediatric non-traumatic rhabdomyolysis.

BACKGROUND: Our study aimed to determine the prevalence of acute kidney injury (AKI) in pediatric non-traumatic rhabdomyolysis, and to identify factors associated with its development. METHODS: Clinical information and laboratory tests of children with rhabdomyolysis who were admitted between 2009 and 2018 were reviewed retrospectively. Rhabdomyolysis was defined by a peak serum creatine kinase (CK) level > 1000 IU/L within the first 72 h of admission. The primary outcome was the occurrence of AKI within the first 7 days of admission, which was determined by the KDIGO criteria. RESULTS: A total of 54 patients with a median age of 7.8 years old were included. Ten (18.5%) patients developed AKI. AKI was relatively rare in children with viral myositis (2.6%), whereas all patients with rhabdomyolysis related to seizure or irritability/dystonia developed AKI. Patients with AKI had higher white cell count (10.6 vs. 4.5 × 109/L) and lower serum bicarbonate (19.4 vs. 25.5 mmol/L) on admission, with higher peak serum CK (23,086.0 vs. 3959.5 IU/L). The AKI group was more likely to present with positive urine results (myoglobinuria, dipstick heme or protein ≥ 2+). Peak serum CK had a good discriminatory power for stage 2-3 AKI (AUC 0.930, p = 0.005), with an optimal cut-off of 15,000 IU/L identified from the ROC analysis. CONCLUSIONS: The overall prevalence of AKI in pediatric non-traumatic rhabdomyolysis was 18.5%. Positive urine tests (myoglobinuria, dipstick heme or protein ≥ 2+), high white cell count, lower serum bicarbonate on admission, and high peak serum CK were associated with development of AKI.

KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update.

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for nutrition in kidney diseases since 1999. Since the publication of the first KDOQI nutrition guideline, there has been a great accumulation of new evidence regarding the management of nutritional aspects of kidney disease and sophistication in the guidelines process. The 2020 update to the KDOQI Clinical Practice Guideline for Nutrition in CKD was developed as a joint effort with the Academy of Nutrition and Dietetics (Academy). It provides comprehensive up-to-date information on the understanding and care of patients with chronic kidney disease (CKD), especially in terms of their metabolic and nutritional milieu for the practicing clinician and allied health care workers. The guideline was expanded to include not only patients with end-stage kidney disease or advanced CKD, but also patients with stages 1-5 CKD who are not receiving dialysis and patients with a functional kidney transplant. The updated guideline statements focus on 6 primary areas: nutritional assessment, medical nutrition therapy (MNT), dietary protein and energy intake, nutritional supplementation, micronutrients, and electrolytes. The guidelines primarily cover dietary management rather than all possible nutritional interventions. The evidence data and guideline statements were evaluated using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. As applicable, each guideline statement is accompanied by rationale/background information, a detailed justification, monitoring and evaluation guidance, implementation considerations, special discussions, and recommendations for future research.

The use of ultrasound to assess aortic biomechanics: Implications for aneurysm and dissection.

Arterial stiffening, which occurs when conduit arteries thicken and lose elasticity, has been associated with cardiovascular disease and increased risk for future cardiovascular events. Specifically, aortic stiffening plays a large role in the pathogenesis of vascular diseases, such as aneurysm formation and dissection. Current parameters used to assess risk of aortic rupture include absolute diameter and growth rate. However, these properties lack the reliability required to accurately risk-stratify patients. As with any elastic conduit, it is important to assess the biomechanical properties of the aorta in order to assess cardiovascular risk and prevent disease progression. There are several invasive and noninvasive methods by which stiffness of the large arteries can be assessed. Of particular interest are ultrasound-based methods, such as tissue Doppler imaging and speckle-tracking echocardiography, due to their noninvasive and feasible nature. In this review, we summarize studies demonstrating utility of noninvasive ultrasound imaging methods for measuring aortic biomechanics for the assessment and management of aortic aneurysms.

Pseudonormalization of the Typical Electrocardiography Repolarization Pattern of a Black Athlete.

Cardiac repolarization of black athletes has a distinctive pattern. During an episode of pericarditis, this pattern may evolve into a "pseudonormalized" electrocardiography (ECG). On resolution of the pericardial inflammation, the ECG may return to the normal variant for a black athlete, sounding the alarms of extended disease to the myocardium. Recognizing the normal variant for a black athlete will reduce the need for unnecessary further testing or treatments. The case is discussed in detail.

Factors that affect ultrasound-determined labor progress in women undergoing induction of labor.

BACKGROUND: The traditional approach to the assessment of labor progress is by digital vaginal examination; however, it is subjective and imprecise. Recent studies have investigated the role of transperineal ultrasonographic assessment of fetal head descent by measuring the angle of progression and head-perineum distance. OBJECTIVE: The objective of this study was to evaluate factors that affected labor progress, which were defined by the transperineal ultrasonographic parameters, in women who achieved vaginal delivery. STUDY DESIGN: This was a prospective longitudinal study performed in 315 women with singleton pregnancy who underwent labor induction at term between December 2016 and December 2017. Paired assessment of cervical dilation and fetal head station by vaginal examination and transperineal ultrasonographic assessment of fetal head descent (parasagittal angle of progression and head-perineum distance) were made serially after the commencement of labor induction until full cervical dilation. The researchers were blinded to the findings of the clinical team's vaginal examination and vice versa. The repeated measure data were analyzed by mixed effect models to identify the significant factors (age ≥35 years, obesity, parity, methods of labor induction, and epidural anesthesia) that affected the relationship between parasagittal angle of progression and head-perineum distance against fetal head station and cervical dilation. RESULTS: The total number of paired vaginal examination and transperineal ultrasonographic assessments among the 261 women (82.9%) with vaginal delivery was 945, with a median of 3 per woman. The median assessment-to-assessment interval was 4.6 hours (interquartile range, 4.3-5.2). Multiparity and mechanical methods of labor induction were associated with a faster rate of fetal head descent, which was determined by head-perineum distance against fetal head station, than nulliparity and the use of a slow-release vaginal pessary, respectively. An additional increase of 0.10 cm in head-perineum distance was observed, for an unit increase in fetal head station in nulliparous women (P=.03) and women who had a slow-release vaginal pessary (P=.02), compared with multiparous women and those who had mechanical methods for labor induction. The use of epidural anesthesia was associated with a slower rate of fetal head descent, which was determined by both parasagittal angle of progression and head-perineum distance, against fetal head station. An additional decrease of 3.66 degrees in parasagittal angle of progression (P=.04) and an additional increase in 0.33 cm in head-perineum distance (P≤.001) were observed for a unit increase in fetal head station in women with the use of epidural anesthesia, compared with those without. Obese women had higher head-perineum distance overall, compared with normal weight women; at different cross-sections of time periods, obesity appeared to be associated with a slower rate of change between head-perineum distance and cervical dilation. Advanced maternal age did not affect transperineal ultrasound-determined labor progress (P>.05). CONCLUSION: Parity, methods of labor induction, the use of epidural anesthesia, and obesity affect labor progress, which has been illustrated objectively by serial transperineal ultrasonographic assessment of fetal head descent.

Labor progress determined by ultrasound is different in women requiring cesarean delivery from those who experience a vaginal delivery following induction of labor.

BACKGROUND: The diagnosis of labor dystocia generally is determined by the deviation of labor progress, which is assessed by the use of a partogram. Recently, intrapartum transperineal ultrasound for the assessment of fetal head descent has been introduced to assess labor progress in the first stage of labor in a more objective and noninvasive way. OBJECTIVE: The objective of the study was to determine the differences in labor progress by the use of serial transperineal ultrasound assessment of fetal head descent between women having vaginal and cesarean delivery. STUDY DESIGN: This was a prospective longitudinal study performed in 315 women with singleton pregnancy who were undergoing labor induction at term between December 2016 and December 2017. Paired assessment of cervical dilation and fetal head station by vaginal examination and transperineal ultrasonographic assessment of parasagittal angle of progression and head-perineum distance were made serially after the commencement of labor induction. According to the hospital protocol, assessment was performed every 24 hours and 4 hours, respectively, during latent and active phases of labor. The researchers and the clinical team were blinded to each other's findings. The repeated measures data were analyzed by mixed effect models. To determine the effect of mode of delivery on the association between parasagittal angle of progression and head-perineum distance against fetal head station and cervical dilation, the significance of the interaction term between each mode of delivery and fetal head station or cervical dilation was determined, which accounted for parity and obesity. Area under receiver-operating characteristic curve was used to evaluate the performance of serial intrapartum sonography in predicting women with cesarean delivery because of failure to progress. RESULTS: The total number of paired vaginal examination and ultrasound assessments was 1198, with a median of 3 per woman. The median assessment-to-assessment interval was 4.6 hours (interquartile range, 4.3-5.1 hours). Women who achieved vaginal delivery (n=261) had steeper slopes of parasagittal angle of progression and head-perineum distance against fetal head station and cervical dilation than those who achieved cesarean delivery (n=54). Objectively, an additional decrease of 5.11 and 1.37 degrees in parasagittal angle of progression was observed for an unit increase in fetal head station and cervical dilation, respectively, in women who required cesarean delivery (P<.01; P=.01), compared with women who achieved vaginal delivery, after taking account of repeated measures from individuals and confounding factors. The respective additional increases in head-perineum distance for a unit increase in fetal head station and cervical dilation were 0.27 cm (P<.01) and 0.12 cm (P<.01). A combination of maternal characteristics with the temporal changes of parasagittal angle of progression for an unit increase in fetal head station achieved an area under receiver-operating characteristic curve of 0.85 (95% confidence interval, 0.76-0.94), with sensitivity of 79% and specificity of 80%, for the prediction of women who required cesarean delivery because of failure to progress. CONCLUSION: The differences in labor progress between vaginal and cesarean delivery have been illustrated objectively by serial intrapartum transperineal ultrasonographic assessment of fetal head descent. This tool is potentially predictive of women who will require cesarean delivery because of failure to progress.

The Associations of Muscle Strength, Muscle Mass, and Adiposity With Clinical Outcomes and Quality of Life in Prevalent Kidney Transplant Recipients.

OBJECTIVE: Sarcopenia, defined as loss of both muscle strength and mass, is associated with inferior clinical outcomes and quality of life (QoL) in chronic kidney disease, but its effects are unknown in kidney transplantation. Obesity confers increased mortality risk and compromises QoL in kidney transplant recipients (KTRs), but the impacts of sarcopenic obesity remain unexplored. This study aimed to evaluate the associations of muscle strength and mass, sarcopenia, and sarcopenic obesity with clinical outcomes and QoL in KTRs. METHODS: This prospective longitudinal study enrolled 128 KTRs ≥1-year posttransplantation. Low muscle strength (by handgrip strength) and mass (by bioimpedance analysis), and a combination of both (sarcopenia) were defined as < reference cutoffs for corresponding indices. Sarcopenic obesity was defined as sarcopenia combined with fulfillment of ≥2 out of 3 criteria from (1) body mass index ≥30 kg/m2, (2) bioimpedance analysis-derived fat mass > reference cutoffs, and (3) waist circumference > World Health Organization cutoffs. Prospective follow-up data on mortality and hospitalization were collected. QoL was evaluated using Medical Outcomes Study Short Form-36 questionnaire. RESULTS: Median follow-up duration was 64 (60-72) months. Low muscle strength was independently associated with the composite endpoint of mortality and hospitalization (hazard ratio = 2.45; P = .006), and QoL (physical-related: ß = -12.2; P = .04; mental-related: ß = -9.9; P = .04). Low muscle mass (ß = -8.8; P = .04) and sarcopenia (ß = -14.7; P = .03) were associated with physical-related QoL only. No independent associations were found between muscle mass, sarcopenia, and sarcopenic obesity with the composite outcome of mortality and hospitalization. CONCLUSION: Low muscle strength is common among KTRs, conferring poor prognosis in the medium term. Future research on strength training may prove valuable in improving kidney transplantation outcomes.

Collecting Unused Medical Supplies in Emergency Departments for Responsible Redistribution.

BACKGROUND: Medical supplies and equipment are unevenly distributed throughout the world. OBJECTIVE: Our aim was to describe, quantify, and monetize unused supplies suitable for recovery produced from two urban emergency departments (EDs). METHODS: We trained ED staff to place opened, unused, uncontaminated medical supplies in strategically located bins located in two urban EDs for 30 days. We sorted and quantified collected supplies, then used hospital-specific supply catalogs to determine the total cost of recovered medical supplies during the 30-day study period. We extrapolated the amount of collected medical supplies and associated costs to yearly estimates. RESULTS: We recovered 39.9 kg ($6,096) from the trauma center and 3.4 kg ($539) from the academic center during the 30-day study period. The most commonly collected supplies included open but unused procedure kits ($1,776), catheter needles ($1,009), and sutures ($698). We estimated that the trauma center produces $73,158 of unused medical supplies per year and the academic center produces $6,467 of unused medical supplies per year. CONCLUSIONS: We present a novel approach to decreasing waste and recovering usable medical supplies, in which we found that substantial, valuable medical supplies can be recovered in two urban EDs.

Pre-Induction Transperineal Ultrasound Assessment for the Prediction of Labor Outcome.

OBJECTIVE: To examine (1) the concordance of manual and automated para-symphyseal angle of progression (psAOP) measurements, (2) the repeatability of psAOP, head-symphysis distance, head-perineum distance, and sonographic cervical dilatation, and (3) the value of transperineal ultrasound (TPU) in predicting induction of labor (IOL) outcome. METHODS: We performed a prospective study in 308 women with singleton pregnancies undergoing IOL at term. Logistic regression analysis was used to determine which maternal factors, Bishop score, method of IOL, and TPU parameters were significant predictors of cesarean section (CS) and CS due to no progress (CS-NP). RESULTS: There was vaginal delivery in 225 (83.0%) and CS in 46 (17.0%) cases. The intra-class correlation coefficient between manual and automated psAOP was 0.866, but automated psAOP was 4.6° wider than manual measurement. All TPU parameters had an inter-observer intra-class correlation coefficient > 0.800. Significant independent prediction of CS and CS-NP was provided by maternal factors, previous vaginal delivery, and psAOP. There was no improvement in area under the receiver-operating characteristic curve with the addition of psAOP to maternal factors. CONCLUSIONS: All TPU parameters are reproducible. Comparing the three TPU parameters for fetal head station, only psAOP is a significant independent predictor of CS; however, it is unlikely to be useful in predicting IOL outcome.

The Associations of Endotoxemia With Systemic Inflammation, Endothelial Activation, and Cardiovascular Outcome in Kidney Transplantation.

OBJECTIVE: Cardiovascular disease is the leading cause of death in kidney transplant recipients (KTRs), yet incompletely accountable by traditional risk factors. Inflammation is an unconventional cardiovascular risk factor, with gut-derived endotoxemia potentially driving inflammation and endothelial disease. Comparable data are lacking in kidney transplantation. This study investigated the associations of endotoxemia with inflammation, endothelial activation, and 5-year cardiovascular events in KTRs. Determinants of endotoxemia were also explored. DESIGN AND METHODS: This is a single-center cross-sectional study with prospective follow-up from a prevalent cohort of 128 KTRs. MAIN OUTCOME MEASURES: Demographic, nutritional and clinical predictors of inflammation (high-sensitivity C-reactive protein [hsCRP]), endothelial activation (sE-selectin), and endotoxemia (endotoxin) were assessed. Follow-up data on 5-year cardiovascular event rates were collected. RESULTS: Endotoxemia (P = .03), reduced 25-hydroxyvitamin D (P = .04), high fructose intake (P < .001), decreased fiber intake (P < .001), and abdominal obesity (P = .002) were independently associated with elevated hsCRP. In turn, endotoxemia (P = .007) and increasing hsCRP (P = .02) were both independently associated with raised sE-selectin. Furthermore, endotoxemia predicted increased cardiovascular event rate (P = .02), independent of hsCRP and a global measure of cardiovascular risk estimated by a validated algorithm of 7-year risk for major adverse cardiac events in kidney transplantation. Determinants of endotoxemia included reduced 25-hydroxyvitamin D (P < .001), hypertriglyceridemia (P < .001), increased fructose intake (P = .01), and abdominal obesity (P = .01). CONCLUSIONS: Endotoxemia in KTRs contributes to inflammation, endothelial activation, and increased cardiovascular events. This study highlights the clinical relevance of endotoxemia in KTRs, suggesting future interventional targets.

Myxoma virus suppresses proliferation of activated T lymphocytes yet permits oncolytic virus transfer to cancer cells.

Allogeneic hematopoietic cell transplant (allo-HCT) can be curative for certain hematologic malignancies, but the risk of graft-versus-host disease (GVHD) is a major limitation for wider application. Ideally, strategies to improve allo-HCT would involve suppression of T lymphocytes that drive GVHD while sparing those that mediate graft-versus-malignancy (GVM). Recently, using a xenograft model, we serendipitously discovered that myxoma virus (MYXV) prevented GVHD while permitting GVM. In this study, we show that MYXV binds to resting, primary human T lymphocytes but will only proceed into active virus infection after the T cells receive activation signals. MYXV-infected T lymphocytes exhibited impaired proliferation after activation with reduced expression of interferon-γ, interleukin-2 (IL-2), and soluble IL-2Rα, but did not affect expression of IL-4 and IL-10. MYXV suppressed T-cell proliferation in 2 patterns (full vs partial) depending on the donor. In terms of GVM, we show that MYXV-infected activated human T lymphocytes effectively deliver live oncolytic virus to human multiple myeloma cells, thus augmenting GVM by transfer of active oncolytic virus to residual cancer cells. Given this dual capacity of reducing GVHD plus increasing the antineoplastic effectiveness of GVM, ex vivo virotherapy with MYXV may be a promising clinical adjunct to allo-HCT regimens.

Tumour genesis syndrome: severe hypophosphatemia and hypokalemia may be ominous presenting findings in childhood acute myeloid leukaemia.

We report a 16-year-old girl who was diagnosed with acute leukaemia and a marked leucocytosis >200 × 109/L. She presented with marked hypophosphatemia, hypokalemia, acute renal failure and acute respiratory failure. These electrolytes disturbances may indicate rapid tumour genesis. These ominous findings required urgent treatment to halt the crises of rapid leukemic cell proliferation. CONCLUSION: Mark hypophosphatemia and hypokalemia may be presenting electrolyte abnormalities in a patient with acute leukaemia, and these may be indicators of aggressive tumour genesis. What is known: • Mild electrolyte disturbances are common in oncology patients • Tumour lysis syndrome is well recognized by paediatriaticians What is new: • Life-threatening hypophosphatemia is an uncommon presentation • These electrolytes disorders may indicate an aggressive tumour genesis process even at presentation and require urgent treatment.

Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease.

Renal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus (PKD1 versus PKD2). Recent studies identified nontruncating PKD1 mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine ≤1.4 mg/dl at recruitment. We screened these families for PKD1 and PKD2 mutations and reviewed the clinical outcomes of the probands and affected family members. Height-adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of PKD1 truncating, PKD1 in-frame insertion/deletion, PKD1 nontruncating, and PKD2 mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with PKD1 truncating mutations, patients with PKD1 in-frame insertion/deletion, PKD1 nontruncating, or PKD2 mutations have smaller htTKV and reduced risks (hazard ratio [95% confidence interval]) of ESRD (0.35 [0.14 to 0.91], 0.10 [0.05 to 0.18], and 0.03 [0.01 to 0.05], respectively) and death (0.31 [0.11 to 0.87], 0.20 [0.11 to 0.38], and 0.18 [0.11 to 0.31], respectively). Refined genotype-renal disease correlation coupled with targeted next generation sequencing of PKD1 and PKD2 may provide useful clinical prognostication for ADPKD.

Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells.

BACKGROUND: Relapsing disease is a major challenge after hematopoietic cell transplantation for hematological malignancies. Myxoma virus (MYXV) is an oncolytic virus that can target and eliminate contaminating cancer cells from auto-transplant grafts. The aims of this study were to examine the impact of MYXV on normal hematopoietic stem and progenitor cells and define the optimal treatment conditions for ex vivo virotherapy. METHODS: Bone marrow (BM) and mobilized peripheral blood stem cells (mPBSCs) from patients with hematologic malignancies were treated with MYXV at various time, temperature and incubation media conditions. Treated BM cells from healthy normal donors were evaluated using flow cytometry for MYXV infection, long-term culture-initiating cell (LTC-IC) assay and colony-forming cell (CFC) assay. RESULTS: MYXV initiated infection in up to 45% of antigen-presenting monocytes, B cells and natural killer cells; however, these infections were uniformly aborted in >95% of all cells. Fresh graft sources showed higher levels of MYXV infection initiation than cryopreserved specimens, but in all cases less than 10% of CD34(+) cells could be infected after ex vivo MYXV treatment. MYXV did not impair LTC-IC colony numbers compared with mock treatment. CFC colony types and numbers were also not impaired by MYXV treatment. MYXV incubation time, temperature or culture media did not significantly change the percentage of infected cells, LTC-IC colony formation or CFC colony formation. CONCLUSIONS: Human hematopoietic cells are non-permissive for MYXV. Human hematopoietic stem and progenitor cells were not infected and thus unaffected by MYXV ex vivo treatment.

Cardiovascular, muscular and perceptual contributions to physical fatigue in prevalent kidney transplant recipients.

Physical fatigue is debilitating and common among kidney transplant recipients (KTRs). This study investigated the mechanistic aetiology of physical fatigue in this setting through examinations of muscle mass, muscular and cardiovascular function, and perceived exertion. The incidence of physical fatigue, its association with quality of life (QoL), and the predictors of perceived exertion, were evaluated. This single-centre observational cross-sectional study enrolled 55 KTRs. Muscle mass was quantified using dual-energy x-ray absorptiometry. Muscular function was assessed by jumping mechanography. Cardiovascular function (maximal oxygen consumption and oxygen pulse) was estimated during submaximal exercise testing, with perceived exertion determined using age-adjusted Borg scale-ratings. Physical fatigue was measured using Multi-Dimensional Fatigue Inventory-20. QoL was assessed using Medical Outcomes Study Short Form-36. Demographic, clinical, nutritional, psychosocial and behavioural predictors of perceived exertion were assessed. Of clinical importance, increased perceived exertion was the only independent predictor of physical fatigue (P = 0.001), with no association found between physical fatigue and muscular or cardiovascular parameters. Physical fatigue occurred in 22% of KTRs, and negatively impacted on QoL (P < 0.001). Predictors of heightened perception included anxiety (P < 0.05) and mental fatigue (P < 0.05). Perception is a key determinant of physical fatigue in KTRs, paving the way for future interventions.