Role of Cachexia and Fragility in the Patient Candidate for Cardiac Surgery

Frailty is the major expression of accelerated aging and describes a decreased resistance to stressors, and consequently an increased vulnerability to additional diseases in elderly people. The vascular aging related to frail phenotype reflects the high susceptibility for cardiovascular diseases and negative postoperative outcomes after cardiac surgery. Sarcopenia can be considered a biological substrate of physical frailty. Malnutrition and physical inactivity play a key role in the pathogenesis of sarcopenia. We searched on Medline (PubMed) and Scopus for relevant literature published over the last 10 years and analyzed the strong correlation between frailty, sarcopenia and cardiovascular diseases in elderly patient. In our opinion, a right food intake and moderate intensity resistance exercise are mandatory in order to better prepare patients undergoing cardiac operation.     

High Case-Fatality Rate for Human Anthrax,Northern Ghana, 2005–2016

The human cutaneous anthrax case-fatality rate is ≈1% when treated, 5%–20% when untreated. We report high case-fatality rates (median 35.0%; 95% CI 21.1%–66.7%) during 2005–2016 linked to livestock handling in northern Ghana, where veterinary resources are limited. Livestock vaccination and access to human treatment should be evaluated.     

A comparison of robotic-assisted splenectomy and laparoscopic splenectomy for children with hematologic disorders

IntroductionLaparoscopic splenectomy (LS) is the standard of care for hematologic disorders requiring splenectomy. Less is known about the outcomes following robotic-assisted splenectomy (RS) for this indication. Our aim was to describe outcomes of RS to LS in pediatric patients with hematologic disorders in our institution.MethodsA single institution retrospective review was performed of pediatric patients undergoing LS vs. RS from 2014 to 2019. Patient demographics, diagnosis, spleen size, hospital length of stay (LOS), operative time, post-operative opioid use, and hospital charges were evaluated. Standard univariate analyses were performed.ResultsTwenty-four patients were included in the study (14 LS, 10 RS). The mean spleen size at the time of surgery was larger in the RS group compared to LS (14.5 cm vs. 12.2 cm, p = 0.03). Operative time between the two cohorts was comparable (RS 140.5 vs LS 154.9 min). Median LOS for RS was shorter than LS (2.1 vs. 3.2 days, p = 0.02). Cumulative postoperative opioid analgesic requirements were not significantly different between the groups (17.4 mg vs. 30.5 mg). The median hospital charges, including the surgical procedure and hospital stay were higher in the RS group ($44,724 RS vs $30,255 LS, p = 0.01).ConclusionRobotic splenectomy is a safe and feasible option for pediatric patients with hematologic disorders, and was associated with decreased LOS but higher charges compared to laparoscopic splenectomy. Further studies are required to delineate the optimal use and potential benefits of robot-assisted surgical techniques in children.Level of EvidenceII.     

The role of multiparametric MRI in active surveillance for low-risk prostate cancer: The ROMAS randomized controlled trial

BackgroundWe aim to evaluate the impact of multiparametric magnetic resonance imaging and fusion-target biopsy for early reclassification of patients with low-risk Prostate Cancer in a randomized trial.Materials and methodsBetween 2015 and 2018, patients diagnosed with Prostate Cancer after random biopsy fulfilling PRIAS criteria were enrolled and centrally randomized (1:1 ratio) to study group or control group. Patients randomized to study group underwent multiparametric magnetic resonance imaging at 3 months from enrollment: patients with positive findings (PIRADS-v2>2) underwent fusion-target biopsy; patients with negative multiparametric magnetic resonance imaging or confirmed ISUP - Grade Group 1 at fusion-target biopsy were managed according to PRIAS schedule and 12-core random biopsy was performed at 12 months. Patients in control group underwent PRIAS protocol, including a confirmatory 12-core random biopsy at 12 months. Primary endpoint was a reduction of reclassification rate at 12-month random biopsy in study group at least 20% less than controls. Reclassification was defined as biopsy ISUP Grade Group 1 in >2 biopsy cores or disease upgrading.ResultsA total of 124 patients were randomized to study group (n = 62) or control group (n = 62). Around 21 of 62 patients (34%) in study group had a positive multiparametric magnetic resonance imaging, and underwent fusion-target biopsy, with 11 (17.7%) reclassifications. Considering the intention-to-treat population, reclassification rate at 12-month random biopsy was 6.5% for study group and 29% for control group, respectively (P < 0.001).ConclusionsThe early employment of multiparametric magnetic resonance imaging for active surveillance patients enrolled after random biopsy consents to significantly reduce reclassifications at 12-month random biopsy.     

Barriers and Facilitators to Lifestyle Intervention Engagement and Weight Loss in People Living With Spinal Cord Injury

Background: Individuals living with spinal cord injury (SCI) have a high prevalence of obesity and unique barriers to healthy lifestyle. Objective: To examine barriers and facilitators to engagement and weight loss among SCI participants enrolled in the Group Lifestyle Balance Adapted for individuals with Impaired Mobility (GLB-AIM), a 12-month intensive lifestyle intervention. Methods: SCI participants (N = 31) enrolled in a wait-list, randomized controlled trial where all participants received intervention between August 2015 and February 2017. Analyses of pooled data occurred in 2020 to examine cross-sectional and prospective associations of hypothesized barriers and facilitators with (1) intervention engagement, comprised of attendance and self-monitoring, and (2) percent weight change from baseline to 12 months. We performed multivariable linear regression on variables associated with outcomes at p < .05 in bivariate analyses and controlled for intervention group. Results: Participants were middle-aged (mean age, 48.26 ± 11.01 years), equally male (50%) and female, White (80.7%), and unemployed (65.6%). In participants who completed baseline surveys (n = 30), dietary self-efficacy explained 26% of variance in engagement (p < .01); among the 12-month study completers (n = 22, 71.0%), relationship issues explained 23% of variance in engagement (p < .01). Money problems, health issues unrelated to SCI, lack of motivation, and experimental group explained 57% of variance in weight loss (p for model < .01), with lack of motivation uniquely explaining 24% of variance (p < .01). Conclusion: Improving engagement and weight loss for persons with SCI in the GLBAIM program may be achieved by addressing lack of motivation, relationship issues, and nutrition self-efficacy.     

A world-wide survey on kidney transplantation practices in breast cancer survivors: The need for new management guidelines

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons’ knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.     

Phase I clinical and pharmacokinetic trial of dextran conjugated doxorubicin (AD-70, DOX-OXD)

Coupling of anthracyclines to high-molecular-weight carriers may alter drug disposition and improve antitumor effects. We have performed a clinical phase I trial of doxorubicin coupled to dextran (70000 m.w.). The drug was administered as single dose i.v. every 21–28 days. Thirteen patients have received a total of 24 courses (median 2; range 1–3). At the starting dose of 40 mg/m² doxorubicin equivalent (DOXeq), WHO grade IV thrombocytopenia was noted in 2/2 patients. WHO grade IV hepatotoxicity and WHO grade III cardiotoxicity were noted in a patient with preexisting heart disease. Five patients were treated with 12.5 mg/m² DOXeq. Maximal toxicity at this dose level was WHO grade III thrombocytopenia and local phlebitis (WHO grade II) in 1/5 patients, elevation of alkaline phosphatase (WHO grade III) and WHO grade III vomiting in another patient. Subsequently, five patients received 20 mg/m² DOXeq. Hepatotoxicity was noted in 5/5 patients (1 × WHO grade IV, 1 × WHO grade III). Thrombocytopenia was noted in 3/5 patients (1 × WHO grade IV, 2 × WHO grade III). At 12.5 mg/m² DOXeq, a patient diagnosed with a malignant fibrous histiocytoma had stable disease for 4 months. Pharmacokinetic analyses of total and free doxorubicin were performed in plasma and urine. The maximum peak plasma concentration (ppc) for total DOX was 12.3 g/ml at 40 mg/m² DOXeq. The area under the plasma concentration time curve (AUC) ranged from 28.83–80.21 g/ml^*h with dose-dependent elimination half lives (t_1/2: 0.02–0.87 h;_1/2: 2.69–11.58 h;_1/2: 41.44–136.58 h). We conclude that the maximal tolerated dose (MTD) of AD-70 using this schedule is 40 mg/m² DOXeq. The recommended dose for clinical phase II studies is 12.5 mg/m² DOXeq.Abbreviations ALT Alanine Aminotransferase - AST Aspartate Aminotransferase - DOX Doxorubicin - DOXeq Doxorubicin Equivalent - ECG Electrocardiogram - HPLC High Pressure Liquid Chromatography - LD₁₀ Lethal Dose for 10% of individuals - MTD Maximal Tolerated Dose - ppc Peak Plasma Concentration - WHO World Health Organisation