Pediatric Cardiology Fellowship Standards for Training in Exercise Medicine and Curriculum Outline.

Over the past 2 decades, fundamentals of exercise medicine, including clinical exercise testing, assessment and promotion of physical activity, exercise prescription, and supervised exercise training/rehabilitation programming have demonstrated considerable clinical value in the management of children and adolescents with congenital and acquired heart disease. Although the principles of exercise medicine have become an integral component in pediatric cardiology, there are no standardized training recommendations for exercise physiology during pediatric cardiology fellowship at this time. Thus, the Pediatric Cardiology Exercise Medicine Curriculum Committee (PCEMCC) was formed to establish core and advanced exercise physiology training recommendations for pediatric cardiology trainees. The PCEMCC includes a diverse group of pediatric cardiologists, exercise physiologists, and fellowship program directors. The expert consensus training recommendations are by no means a mandate and are summarized herein, including suggestions for achieving the minimum knowledge and training needed for general pediatric cardiology practice.

Women, Younger Clinicians', and Caregivers' Experiences of Burnout and Well-being During COVID-19 in a US Healthcare System.

BACKGROUND: The COVID-19 pandemic brought rapid changes to the work and personal lives of clinicians. OBJECTIVE: To assess clinician burnout and well-being during the COVID-19 pandemic and guide healthcare system improvement efforts. DESIGN: A survey asking about clinician burnout, well-being, and work experiences. PARTICIPANTS: Surveys distributed to 8141 clinicians from June to August 2020 in 9 medical groups and 17 hospitals at Sutter Health, a large healthcare system in Northern California. MAIN MEASURES: Burnout was the primary outcome, and other indicators of well-being and work experience were also measured. Descriptive statistics and multivariate logistic regression analyses were performed. All statistical inferences were based on weighted estimates adjusting for response bias. KEY RESULTS: A total of 3176 clinicians (39.0%) responded to the survey. Weighted results showed 29.2% reported burnout, and burnout was more common among women than among men (39.0% vs. 22.7%, p<0.01). In multivariate models, being a woman was associated with increased odds of reporting burnout (OR=2.19, 95% CI: 1.51-3.17) and being 55+ years old with lower odds (OR=0.54, 95% CI: 0.34-0.87). More women than men reported that childcare/caregiving was impacting work (32.9% vs. 19.0%, p<0.01). Even after controlling for age and gender, clinicians who reported childcare/caregiving responsibilities impacted their work had substantially higher odds of reporting burnout (OR=2.19, 95% CI: 1.54-3.11). Other factors associated with higher burnout included worrying about safety at work, being given additional work tasks, concern about losing one's job, and working in emergency medicine or radiology. Protective factors included believing one's concerns will be acted upon and feeling highly valued. CONCLUSIONS: This large survey found the pandemic disproportionally impacted women, younger clinicians, and those whose caregiving responsibilities impacted their work. These results highlight the need for a holistic and targeted strategy for improving clinician well-being that addresses the needs of women, younger clinicians, and those with caregiving responsibilities.

A multiplex real-time PCR assay for routine diagnosis of bacterial vaginosis.

A semi-quantitative multiplex PCR assay for the diagnosis of bacterial vaginosis (BV) was evaluated in a prospective study in a population of Dutch women with complaints of abnormal vaginal discharge. The PCR targets Gardnerella vaginalis, Atopobium vaginae, Megasphaera phylotype 1, Lactobacillus crispatus and Lactobacillus iners. Together with a short questionnaire, a vaginal swab for PCR and vaginal smear for microscopy were taken by their general practitioner or gynaecologist. Data from 151 women (median age 32) were available. Nugent Score (NS) was used to classify the samples and 83 samples were classified as normal (NS 0-3), 13 as intermediate (NS 4-6), and 55 as bacterial vaginosis (NS 7-10). In women with a NS of 7-10, PCR detected Gardnerella vaginalis, Atopobium vaginae and Megasphaera phylotype 1 in respectively, 96 %, 87 % and 60 %, whereas in women with a NS of 1-3 these species were detected in 27 %, 6 % and 2 % (P <0.001). A ratio of Lactobacillus crispatus over Lactobacillus iners of <1 (as calculated from the quantification cycle value (Cq)) was present in women with a NS of 7-10 in 66 % versus 33 % in women with a NS of 1-3 (P <0.001). The BV-PCR displayed a sensitivity of 92 % and specificity of 96 % with a positive predictive value of 94 % and a negative predictive value of 95 %. The Lactobacillus-index improved the correct classification of samples where only one of the other bacterial species was detected. Compared to the Nugent Score this multiplex qPCR offers a convenient tool for performing observer independent diagnosis of BV.

Enhanced degradation of tryptophan in patients on hemodialysis.

BACKGROUND: Hemodialysis patients often present with increased concentrations of tryptophan catabolites perhaps related to an enhanced activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) that is inducible by pro-inflammatory stimuli. The often chronic inflammation and immune activation status in dialysis patients may accelerate tryptophan degradation, which could influence patients' psychological performance. PATIENTS AND METHODS: In this study, plasma concentrations of kynurenine and tryptophan were determined by HPLC in 75 dialysis patients, aged 65.3 ± 15.0 years. Forty patients were female, 35 male; 21 (28%) had diabetes mellitus Type 1 or 2 and 32 (43%) suffered from sleep disturbances and/or depression. Their dialysis vintage was 4.26 ± 4.72 years. HPLC results were compared to concentrations obtained from 40 healthy blood donors, to immune activation marker neopterin, and to psychological test results based on INTERMED scores. RESULTS: Compared to those in healthy controls, tryptophan concentrations were decreased in patients. Neopterin, kynurenine and the kynurenine to tryptophan ratio (kyn/trp, an index of tryptophan degradation) were increased in patients (all p < 0.01). Kyn/trp correlated with neopterin concentrations (rs = 0.393, p < 0.01). INTERMED scores were 21.0 + 8.4 and slightly higher in females (U = -1.831, p < 0.07); they correlated with tryptophan concentrations (rs = -0.227, p < 0.05) but with no other parameter studied. Data point to a possible relationship between tryptophan metabolic disturbances and psychologic presentation of patients, although only a rather weak relationship was found. CONCLUSION: We conclude that tryptophan degradation is increased in dialysis patients. The association with increased neopterin concentrations indicates activated IDO.

[Oncologic outcomes after radical prostatectomy: French validation of the D'Amico risk group classification]. / Résultats carcinologiques après prostatectomie totale pour cancer: validation française de la classification de D'Amico.

PURPOSE: To validate the D'Amico risk group classification in French consecutive series and to analyse recurrence risk factor after radical prostatectomy (RP) for prostate cancer. MATERIAL: We retrospectively analyzed data collected from 10/2000 to 05/2009 for 730 consecutive patients who underwent RP for clinically localized or locally advanced prostate cancer (cT1-cT3) in our institution. Biochemical recurrence (BCR) was defined by prostate-specific antigen (PSA) of greater than 0.1 ng/ml, with rising PSA at two consecutive dosages. Postoperative survival was estimated using the Kaplan-Meier method after D'Amico's group stratification. The accuracy of the model was evaluated using the Harrell's concordance index. The impact on outcomes of preoperative PSA and pathological features was evaluated using a monovariate and multivariate Cox analysis. RESULTS: Median follow-up was 30 months [interquartile range: 13-51]. The overall 3-year and 5-year probability of freedom from BCR was 85% (95% Confidence Interval (CI), 81-88%) and 78% (95% CI, 74-83%), respectively. For low, intermediate, and high-risk group, the 5-year freedom from BCR was 92% (95% CI, 88-97%), 73% (95% CI, 65-81%) and 44% (95% CI, 28-59%), respectively (p<0.001). Harrell's concordance index was 0.71. Surgical margins were positive in 31% of all cases. In a multivariate analysis, preoperative PSA, pathological tumor stage, Gleason score and surgical margins status predicted BCR after RP. CONCLUSIONS: We externally validated the ability of the D'Amico's risk group stratification to predict disease progression following RP in European patients. Preoperative PSA, pathological stage, Gleason score and surgical margins status predicted BCR after RP in our series through a multivariate analysis.

[Sporadic upper urinary tract urothelial cell carcinomas: identification of interaction between toxic carcinogens and individuals genetic susceptibility]. / Tumeurs des voies excrétrices urinaires supérieures sporadiques: identification de l'interaction entre l'exposition aux carcinogènes environnementaux et la susceptibilité génétique des individus.

Upper urinary tract urothelial cell carcinomas (UUT UCC) are rare sporadic tumors. Recent epidemiologic and molecular data have shown a singular susceptibility of UUT UCCs for specific risk factors. The main exogenic factors involved in UUT UCCs carcinogenesis remain tobacco and occupational exposure (aromatic amines, polycyclic hydrocarbures and chlored solvents). Enzymatic variants of detoxification system may be responsible of carcinogenesis with these toxics. Tumors induced by phenacetine consumption are decreasing since it was banned in the 1970s. Also, acid aristolochic exposure (Balkan nephropathy, Chinese Herb nephropathy) has been demonstrated to specifically induce UUT UCCs. Familial genic polymorphism of detoxification system would explain geographic distribution in endemic areas. In Taiwan, chronic arsenic exposition would constitute the main risk factor of UUT UCC. However, theses mechanisms of carcinogenesis remain unclear. The knowledge of UUT UCC development mechanisms implying toxic detoxification systems is still incomplete. To date, there is a growing body of evidence supporting that the interaction between individual genetic susceptibilities and environmental toxic exposure is a key to explain carcinogenesis in the majority of sporadic UUT UCC occurrence.

Development of a fluorescence-based assay for screening of modulators of human organic anion transporter 1B3 (OATP1B3).

The organic anion transporting protein 1B3 (OATP1B3), formerly termed OATP8, is responsible for uptake and subsequent elimination of multiple amphipathic drugs by the liver. In silico methods for the prediction of transport rates for drugs and drug-like molecules might provide an important tool in drug development. Most prediction methods however require a large training set of in vitro experimental data in order to yield reliable results. To obtain these data, we have developed a fluorescence-based assay that allows screening a relatively high number of substances for their transporter affinity. HEK293 cells overexpressing OATP1B3 (HEK-OATP8) [Y. Cui, J. Konig, D. Keppler, Vectorial transport by double-transfected cells expressing the human uptake transporter SLC21A8 and the apical export pump ABCC2, Mol. Pharmacol. 60 (2001) 934-943.] were tested for transport of Fluo-3. Fluo-3 uptake could be seen in a concentration-dependent manner. Uptake can be inhibited completely by the addition of the known OATP1B3-inhibitor rifampicin proving that Fluo-3 is transported by OATP1B3. To verify the suitability of the system to identify modulators of OATP1B3, we tested known substrates for competitively inhibiting the Fluo-3 transport by giving them simultaneously with a 2muM Fluo-3-solution to the cells. The transport of Fluo-3 was decreased by all test substrates in a concentration dependent manner.

Bone mineral densitometry in dialyzed patients: quantitative computed tomography versus dual photon absorptiometry.

Reduced bone mineral density (BMD) increases risk of fractures, thus making it necessary to monitor patients suffering from chronic renal failure and consecutive disturbance of bone metabolism. In order to evaluate the reliability of available methods, bone mineral density of the lumbar spine assessed with single energy computed tomography (QCT) was compared with bone mineral density of the lumbar spine, femoral neck, Ward's triangle and trochanteric region measured by dual energy photon absorptiometry (DPA) in 45 hemodialyzed patients with a mean hemodialysis duration of 35 +/- 26 months (SD). Depending on the measurement site and method 4-34% of dialyzed patients suffered from reduced BMD (z-score < -2). The highest correlation (r = 0.61, p < 0.01) was found between QCT of the spine, trabecular bone, and DPA of Ward's triangle. One year after baseline measurement bone mineral density was reassessed after randomization to either QCT or DPA in 14 and 18 patients, respectively. Whereas lumbar spine and femoral neck did not change, mean BMD showed a decrease at the measurement sites of Ward's triangle (DPA), trochanteric region (DPA) and trabecular bone of the spine (QCT), which, however, was statistically not significant. Cortical BMD of the spine assessed with QCT showed an increase. Although there is some reduction in bone density at most sites in hemodialyzed patients, no significant bone loss could be demonstrated over the course of 1 year.

Immediate and six-month results of the profile of the Amplatzer septal occluder as assessed by transesophageal echocardiography.

Catheter closure of secundum atrial septal defect (ASD) using the Amplatzer septal occluder (ASO) is a potential alternative for open surgical repair. However, the large profile of the device obtained immediately after closure continues to raise some concerns regarding its long-term safety. To evaluate the changes in the profile of the device after being deployed, transesophageal echocardiography was performed in 70 patients (17 men and 53 women) who underwent catheter closure of ASDs immediately after and at 6-month follow-up. The median age at closure was 16 years (range 1.9 to 75) and the median size of the ASD as assessed by transesophageal echocardiography was 14 mm (range 3 to 25). The thickness (profile) of the device was assessed in the 4-chamber, short- and long-axis views of the interatrial septum, and measured at its middle and at the junction of the waist with the disc at its 2 ends. Seventy-three devices were deployed in the 70 patients. The median size of the device was 19 mm (range 8 to 34). Complete closure was achieved in 81.4% and 91.4% immediately after and at 6-months follow-up, respectively. The thickness of the device at its middle decreased from 12.2 +/- 4.3, 12.2 +/- 3.7, and 12.5 +/- 4.3 mm in the 4-chamber, short- and long-axis views to 6.5 +/- 2.0, 6.3 +/- 1.9, and 6.5 +/- 2.2 mm, respectively. The thickness of the device at its superior, inferior, anterior, and posterior edges also decreased by 41.8% +/- 14.0% to 43.7% +/- 9.8%. The changes in the thickness were related to device size. Larger devices were thicker after being deployed. We conclude that the thickness of the ASO decreases by 42% to 48% within 6 months after deployment, resulting in a lower profile.

About 8-hour variation of circulating human endothelin-1.

Plasma endothelin-1 (ET-1) and cortisol were measured around the clock at hourly intervals on 7 clinically healthy, diurnally active, nocturnally resting subjects 22-27 years of age. The circadian rhythm in cortisol is demonstrated for each subject (p < or = 0.020) as well as on a group basis (p = 0.002), peaking in the morning. By contrast, the circadian variation of ET-1 is statistically significant in only one of the subjects, and it is not detected for the group as a whole (p > 0.20). Instead, ET-1 is characterized by an about 8-h component (p < 0.001) that is not found for cortisol.

The large window ductus: a surgical trap.

A rare window type of patent ductus arteriosus is reported that was large (15 mm in maximal transverse dimension) but had virtually no length and hence was externally invisible. The smaller aortic isthmus (4 mm in diameter), which was intrapericardial, was mistaken for the ductus and was inadvertently clip-occluded, leading to death. After a specific diagnosis is made, the large window ductus should be patched on cardiopulmonary bypass with a transpulmonary approach.

[Double photon absorptiometry in renal osteodystrophy]. / Doppel-Photonen-Absorptiometrie bei renaler Osteopathie.

Bone mineral content (BMC) of the lumbar spine (L2-L4), femoral neck, Ward's triangle and the trochanteric region was measured in 52 consecutive patients on maintenance haemodialysis. In the whole group the median BMC value as percentage of sex- and age-matched normal means was significantly decreased only in Ward's triangle (91.7%; p less than 0.02). In patients with chronic interstitial nephritis there was a significant decrease in bone density in Ward's triangle and the trochanteric region (p less than 0.02). There was no correlation between BMC and time on dialysis or intact parathormone. BMC value did not predict the type of renal osteodystrophy, according to Delling. 17 patients underwent a second investigation after one year. There was a slight fall in mean BMC of the lumbar spine (-0.9%) and Ward's triangle (-1.1%). The fall in mean BMC of the trochanteric region was pronounced (-3.2%). We believe that the observed low demineralisation, which was more pronounced in patients with interstitial nephritis, may be attributable to early and carefully monitored therapy with vitamin D metabolites.

[Diagnostic image (197). A man who suddenly collapsed]. / Diagnose in beeld (197). Een plotseling gecollabeerde man.

A 40-year-old man suffered a witnessed collapse with brief loss of consciousness, due to electrical injury.

Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma.

Follicular lymphoma exhibits intratumoral infiltration by non-malignant T lymphocytes, including CD4+CD25+ regulatory T (T(reg)) cells. We combined denileukin diftitox with rituximab in previously untreated, advanced-stage follicular lymphoma patients anticipating that denileukin diftitox would deplete CD25+ T(reg) cells while rituximab would deplete malignant B cells. Patients received rituximab 375 mg/m(2) weekly for 4 weeks and denileukin diftitox 18 mcg/kg/day for 5 days every 3 weeks for 4 cycles; neither agent was given as maintenance therapy. Between August 2008 and March 2010, 24 patients were enrolled. One patient died before treatment was given and was not included in the analysis. Eleven of 23 patients (48%; 95% confidence interval (CI): 27-69%) responded; 2 (9%) had complete responses and 9 (39%) had partial responses. The progression-free rate at 2 years was 55% (95%CI: 37-82%). Thirteen patients (57%) experienced grade ≥3 adverse events and one patient (4%) died. In correlative studies, soluble CD25 and the number of CD25+ T cells decreased after treatment; however, there was a compensatory increase in IL-15 and IP-10. We conclude that although the addition of denileukin diftitox to rituximab decreased the number of CD25+ T cells, denileukin diftitox contributed to the toxicity of the combination without an improvement in response rate or time to progression.