Citations

Alternative models of cardiac rehabilitation (CR) delivery, such as home or community-based programs, have been developed to overcome underutilization. However, their availability and characteristics have never been assessed globally. In this cross-sectional study, a piloted survey was administered online to CR programs globally. CR was available in 111/203 (54.7%) countries globally; data were collected in 93 (83.8% country response rate). 1082 surveys (32.1% program response rate) were initiated. Globally, 85 (76.6%) countries with CR offered supervised programs, and 51 (45.9%; or 25.1% of all countries) offered some alternative model. Thirty-eight (34.2%) countries with CR offered home-based programs, with 106 (63.9%) programs offering some form of electronic CR (eCR). Twenty-five (22.5%) countries with CR offered community-based programs. Where available, programs served a mean of 21.4% ± 22.8% of their patients in home-based programs. The median dose for home-based CR was 3 sessions (Q25−Q75 = 1.0–4.0) and for community-based programs was 20 (Q25–Q75 = 9.6–36.0). Seventy-eight (47.0%) respondents did not perceive they had sufficient capacity to meet demand in their home-based program, for reasons including funding and insufficient staff. Where alternative CR models are offered, capacity is insufficient half the time. Home-based CR dose is insufficient to achieve health benefits. Allocation to program model should be evidence-based.

Selective serotonin reuptake inhibitors are a commonly used and often effective class of medications in the treatment of mood disorders such as anxiety and depression. Sertraline (1S,4S-N-methyl-4-[3,4-dichlorophenyl]-1,2,3,4-tetrahydro-1-naphthylamine [Zoloft; Pfizer, New York City, NY]) is a frequently used selective serotonin reuptake inhibitor that has shown efficacy in children, adolescents, and adults. We report the case of a 13-year-old boy with sertraline-induced rhabdomyolysis and renal failure, trismus, and cardiopulmonary arrest. Pharmacogenetic testing later revealed our patient had serotonin transporter polymorphisms and enzymatic alterations that put him at risk for increased levels of sertraline and greater likelihood for untoward side effects.

Screening for hepatopulmonary syndrome (HPS) using pulse oximetry is recommended in liver transplant (LT) candidates because mortality is increased, independently of the severity of the oxygenation defect. LT exception points may be afforded to those with HPS and severe hypoxemia. We assessed the screening characteristics of pulse oximetry for HPS. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study of adults undergoing their first LT evaluation. Patients underwent protocolized assessment of oxygen saturation by pulse oximetry (SpO2), arterial blood gas, spirometry, and contrast‐enhanced echocardiography (CE). HPS was defined as an alveolar‐arterial gradient ≥15 mm Hg (≥20 mm Hg if age >64 years), intrapulmonary vascular dilatation on CE, and absence of lung disease. The study sample included 363 patients. Of these, 75 (20.7%; 95% confidence interval [CI], 16.6%‐25.2%) met the criteria for HPS. The area under the receiver operating characteristic curve (or c‐statistic) for SpO2 in discriminating HPS was 0.59 (95% CI, 0.51‐0.66). An SpO2 <96%, recommended by practice guidelines as a threshold to require further testing, had low sensitivity (28%; 95% CI, 18%‐28%). The c‐statistic of SpO2 in discriminating HPS with a partial pressure of oxygen (PaO2) <60 mm Hg (eligible for LT exception points) was 0.76 (95% CI, 0.46‐1.00). An SpO2 cutoff of <96% had higher sensitivity for detecting HPS with PaO2 <60 mm Hg (71%; 95% CI, 38%‐100%) but was still inadequate. Conclusion: Pulse oximetry is not sufficiently sensitive to screen for HPS in LT candidates. Arterial blood gas and CE are required in LT candidates for diagnosis of HPS.

BackgroundGraft‐versus‐host disease (GVHD) following solid organ transplantation (SOT) is extremely rare and infrequently described in the dermatologic literature.MethodsWe performed a retrospective clinicopathologic review of our institution's experience with patients diagnosed with SOT‐associated GVHD (SOT GVHD) (May 1, 1996 to September 1, 2017).ResultsOf nine patients with SOT GVHD, seven had undergone liver transplantation, while two had undergone lung transplantation. All presented initially with a skin eruption, which developed an average of 63 days (range: 11‐162 days) post transplant. The average time to diagnosis following the onset of the skin eruption was 12 days (range: 0‐54 days). Diagnosis was often delayed because of a competing diagnosis of drug reaction. Frequent skin findings included pruritic erythematous to violaceous macules and papules with desquamation. Histopathology showed vacuolar interface dermatitis in 12 of 15 cases (80.0%). Of the 11 specimens in which a hair follicle was present for evaluation, vacuolar interface changes around the hair follicle were present in eight (72.7%) cases. Seven patients (77.8%) died from complications during the follow‐up period.ConclusionsSOT GVHD presents initially with skin involvement, is associated with vacuolar interface changes on skin biopsy, and is associated with a high mortality rate. Clinicopathologic correlation is required for accurate diagnosis.

AbstractWe propose that in the microenvironment of inflammatory tissues, including tumours, extracellular proteinases can modulate cell signalling in part by regulating proteinase-activated receptors (PARs). We have been exploring this mechanism in a variety of inflammation and tumour-related settings that include tumour-derived cultured cells from prostate and bladder cancer, as well as immune inflammatory cells that are involved in the pathology of inflammatory diseases including multiple sclerosis. Our work showed that proteinase signalling via the PARs affects prostate and bladder cancer-derived tumour cell behaviour and can regulate calcium signalling in human T-cell and macrophage-related inflammatory cells as well as in murine splenocytes. Further, we found that the tumour-derived prostate cancer cells and immune-related cells (Jurkat, THP1, mouse splenocytes) can produce PAR-regulating proteinases (including kallikreins: kallikrein-related peptidases), that can control tissue function by both a paracrine and autocrine mechanism. We suggest that this PAR-driven signalling process involving secreted microenvironment proteinases can play a key role in cancer and inflammatory diseases including multiple sclerosis.