Long-term administration of low-dose selenium nanoparticles with different sizes aggravated atherosclerotic lesions and exhibited toxicity in apolipoprotein E-deficient mice.

Exploration of long-term in vivo effects of nanomaterials, particularly those with potential biomedical applications, is quite important for better understanding and evaluating their biosafety. Selenium nanoparticles (SeNPs) has been considered as a good candidate in biomedical applications due to its high bioavailability, considerable biological activity, and low toxicity. However, its long-term biological effects and biosafety remain unknown. Our previous study demonstrated that 8-week supplementation with SeNPs (50 µg Se/kg/day) was safe and had an anti-atherosclerotic activity in apolipoprotein E-deficient (ApoE-/-) mice, a well-known animal model of atherosclerosis. As a chronic disease, atherosclerosis needs long-term drug therapy. The aim of this study is to investigate the long-term effects of SeNPs with different sizes on atherosclerotic lesions and their biosafety in ApoE-/- mice fed with a high fat diet. Unexpectedly, the results showed that 24-week administration of SeNPs even at a low dose (50 µg Se/kg/day) aggravated atherosclerotic lesions. Furthermore, SeNPs exacerbated oxidative stress by inhibiting the activities of antioxidant enzymes and the expression of antioxidant selenoenzymes. SeNPs also exacerbated hyperlipidaemia by inducing hepatic lipid metabolic disorder. In the meanwhile, SeNPs aggravated organ injury, especially liver and kidney injury. The above adverse effects of SeNPs were size dependent: SeNPs with the size of 40.4 nm showed the highest adverse effects among the SeNPs with three sizes (23.1 nm, 40.4 nm, and 86.8 nm). In conclusion, the present work shows that long-term administration of low-dose SeNPs aggravated atherosclerotic lesions by enhancing oxidative stress and hyperlipidaemia in ApoE-/- mice, indicative of cardiovascular toxicity. Moreover, long-term administration of SeNPs led to injury to liver and kidney. These results offer novel insights for better understanding the biosafety of SeNPs and other biomedical nanomaterials.

Effect of Early High-Dose Vitamin D3 Repletion on Cognitive Outcomes in Critically Ill Adults.

BACKGROUND: Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. RESEARCH QUESTION: Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function? STUDY DESIGN AND METHODS: This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group. RESULTS: Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42). INTERPRETATION: In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov.

Does COVID-19 Vaccination Warrant the Classical Principle "ofelein i mi vlaptin"?

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses' infections and vaccine technologies, combined with the global vaccines' application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines' efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists' and clinicians' interest for an optimal, individualized, and holistic management of this unprecedented pandemic.

Survival and risk of recurrence of takotsubo syndrome.

OBJECTIVE: The goal of this study is to evaluate the long-term outcomes of patients with takotsubo syndrome and assess factors associated with death or recurrence. METHODS: This is a retrospective population-based cohort study of consecutive patients who presented to an integrated health system in Southern California with takotsubo syndrome between 2006 and 2016. Medical records were manually reviewed to confirm diagnosis and to identify predisposing factors, medication treatment and long-term outcomes. Factors associated with death or recurrent takotsubo syndrome were tested using Cox regression models. RESULTS: Between 2006 and 2016, there were 519 patients with a confirmed diagnosis of takotsubo syndrome. Patients were followed for 5.2 years (IQR 3.0-7.2). During the follow-up period, 39 (7.5%) had recurrent takotsubo syndrome and 84 (16.2%) died. In multivariate modelling, factors associated with higher risk of recurrence or death were age (HR 1.56 per 10-year increase, 95% CI 1.29 to 1.87), male sex (HR 2.52, 95% CI 1.38 to 4.60), diabetes (HR 1.6, 95% CI 1.06 to 2.43), pulmonary disease (HR 2.0, 95% CI 1.37 to 2.91) and chronic kidney disease (HR 1.58, 95% CI 1.01 to 2.47). Treatment with beta-blockers were associated with lower risk of recurrence or death (HR 0.46, 95% CI 0.29 to 0.72). No association was observed between treatment with ACE inhibitors or angiotensin-receptor blockers and recurrence or death (HR 0.92, 95% CI 0.59 to 1.42). CONCLUSIONS: Recurrent takotsubo syndrome occurred in a minor subset of patients. Treatment with beta-blocker was associated with higher event-free survival.

Implementing Patient-Centered Trauma-Informed Care for the Perinatal Nurse.

Adverse childhood experiences and trauma significantly impact physical and mental health. Increased maternal perinatal depression/anxiety, preterm labor, and low birth weight, as well as infant morbidity and mortality, are some examples of the impact of trauma on perinatal health. Trauma-informed care begins with knowledge about trauma, the ability to recognize signs of a trauma response, responding to patients effectively, and resisting retraumatization. As holistic providers, perinatal nurses can create safe care environments, establish collaborative patient relationships based on trust, demonstrate compassion, offer patients options when possible to support patient autonomy, and provide resources for trauma survivors. This can prevent or reduce the negative impact of trauma and improve the health and well-being of infants, mothers, and future generations. This clinical article outlines key strategies for implementation of patient-centered trauma-informed perinatal nursing care.

Assessment of Radiation Doses Delivered to Organs at Risk Among Patients With Early-Stage Favorable Hodgkin Lymphoma Treated With Contemporary Radiation Therapy.

Importance: Response-adapted randomized trials have used positron emission tomography-computed tomography to attempt to identify patients with early-stage favorable Hodgkin lymphoma (ESFHL) who could be treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiation therapy (RT). While maximal efficacy is demonstrated with combined modality therapy, RT is often omitted in fear of late adverse effects; however, the application of modern RT could limit these toxic effects. Objective: To determine the radiation doses delivered to organs at risk with modern involved-site RT among patients with ESFHL treated with 20 Gy after 2 cycles of ABVD. Design, Setting, and Participants: This case series included 42 adult patients with ESFHL (according to the German Hodgkin Study Group criteria) who were treated between 2010 and 2019, achieved complete response by positron emission tomography-computed tomography (1-3 on 5-point scale) following 2 cycles of ABVD, and then received consolidative RT. The study was conducted at a single comprehensive cancer center. Exposures: 2 cycles of chemotherapy followed by 20-Gy involved-site RT. Main Outcomes and Measures: The medical records of patients with ESFHL were examined. Organs at risk were contoured, and doses were calculated. Progression-free survival, defined from date of diagnosis to disease progression, relapse, or death, and overall survival were estimated using the Kaplan-Meier method. Results: The cohort comprised 42 patients with ESFHL (median [range] age at diagnosis, 35 [18-74] years; 18 [43%] women; 24 [57%] with stage II disease). At a median follow-up of 44.6 (95% CI, 27.6-61.6) months, the 3-year progression-free survival and overall survival rates were 91.2% (95% CI, 74.9%-97.1%) and 97.0% (95% CI, 80.4%-99.6%), respectively. The mean heart dose was less than 5 Gy (mean, 0.8 Gy; SD, 1.5 Gy; range, 0-4.8 Gy) in all patients. The mean (SD) breast dose for both breasts was 0.1 (0.2) Gy (left breast range, 0-1.0 Gy; right breast range, 0-0.9 Gy). Conclusions and Relevance: In this study, combined modality therapy with 2 cycles of ABVD and 20 Gy for ESFHL was highly effective and avoided excess doses to organs at risk, which may limit long-term toxic effects.

Aristolochia Herbs and Iatrogenic Disease: The Case of Portland's Powders.

Aristolochia herbals have a 2500-year history of medicinal use. We focused this article on Portland's Powders, an 18th-century British gout medicine containing Aristolochia herbs. The powders constitute an 18th-century iteration of an herbal remedy, which was used, with variations, since at least the fifth century BCE. The use of Portland's Powders in Great Britain may appear to be an unusual choice for investigating a public health problem currently widespread in Asia. Yet it exemplifies long-term medicinal use of Aristolochia herbs, reflecting our argument that aristolochic acid nephropathy (AAN) is a historically persistent iatrogenic disease. Moreover, we provide compelling evidence that individuals taking Portland's Powders for gout would have ingested toxic quantities of aristolochic acid, which causes AAN and cancer. Several factors, including long history of use, latency of toxic effects, and lack of effective regulation, perpetuate usage of Aristolochia herbals to the present day.

Factors of post-stroke dementia: A nationwide cohort study in Taiwan.

AIM: We investigated the long-term risk of dementia for up to 10 years in patients with stroke and broadened the correlates. METHODS: We carried out a case-control study using the Taiwan National Health Insurance Research database in 2000 with a sampled population of 1 million. The study cohort comprised 8236 patients with stroke and no dementia history. We carried out a 1:1 case-control matched analysis on estimated propensity scores. Cox proportional hazards regressions were carried out to estimate the risk of dementia during the 5- and 10-year follow-up periods. The risk factors were also investigated. RESULTS: The stroke cohort was significantly at more risk of dementia during the 5- and 10-year follow-up periods, with adjusted hazard ratios 1.87 and 1.53, respectively. The patients with ischemic stroke, transient ischemic attack and intracerebral hemorrhage had a significantly higher risk of dementia after 5 and 10 years, with adjusted hazard ratios of 1.81 and 1.49, 1.92 and 1.61, and 2.14 and 1.61, respectively. The significant risk factors of dementia were age ≥60 years, resident in southern and eastern regions, having low insurance range, and antiplatelet use. CONCLUSIONS: Stroke and the subtypes, including ischemic stroke, transient ischemic attack and intracerebral hemorrhage, increase the long-term risk of dementia. The incidence of post-stroke dementia increases yearly, but the relative risk decreases gradually. Older adults, residents in southern and eastern regions, having low insurance range and antiplatelet use were prominent risk factors of post-stroke dementia in Taiwan. Careful management of stroke and risk factors of post-stroke dementia with long-term follow up of cognition should be reinforced. Geriatr Gerontol Int 2019; 19: 815-822.

Optimum lesion set and predictors of outcome in persistent atrial fibrillation ablation: a meta-regression analysis.

AIMS: Ablation of persistent atrial fibrillation (PsAF) has been performed by many techniques with varying success rates. This may be due to ablation techniques, patient demographics, comorbidities, and trial design. We conducted a meta-regression of studies of PsAF ablation to elucidate the factors affecting atrial fibrillation (AF) recurrence. METHODS AND RESULTS: Databases were searched for prospective studies of PsAF ablation. A meta-regression was performed. Fifty-eight studies (6767 patients) were included. Complex fractionated atrial electrogram (CFAE) ablation reduced freedom from AF by 8.9% [95% confidence interval (CI) -15 to -2.3, P = 0.009). Left atrial appendage [LAA isolation (three study arms)] increased freedom from AF by 39.5% (95% CI 9.1-78.4, P = 0.008). Posterior wall isolation (PWI) (eight study arms) increased freedom from AF by 19.4% (95% CI 3.3-38.1, P = 0.017). Linear ablation or ganglionated plexi ablation resulted in no significant effect on freedom from AF. More extensive ablation increased intraprocedural AF termination; however, intraprocedural AF termination was not associated with improved outcomes. Increased left atrial diameter was associated with a reduction in freedom from AF by 4% (95% CI -6.8% to -1.1%, P = 0.007) for every 1 mm increase in diameter. CONCLUSION: Linear ablation, PWI, and CFAE ablation improves intraprocedural AF termination, but such termination does not predict better long-term outcomes. Study arms including PWI or LAA isolation in the lesion set were associated with improved outcomes in terms of freedom from AF; however, further randomized trials are required before these can be routinely recommended. Left atrial size is the most important marker of AF chronicity influencing outcomes.

[Association between prescription of long-term systemic glucocorticoid therapy associated measures and prescriber's medical speciality]. / Prescription des mesures adjuvantes aux corticothérapies systémiques prolongées en fonction de la spécialité du prescripteur.

INTRODUCTION: In order to prevent some glucocorticoid-induced adverse events, adjuvant measures are often associated with prescription of long-term (≥3 months) systemic glucocorticoid therapy. The main objective of this study was to study the association between prescription of these measures and the medical specialty of the prescriber. METHODS: A cross-sectional study was conducted through the website www.cortisone-info.fr. Patients visiting this website and receiving long-term glucocorticoid therapy were asked to fill a questionnaire asking them, among other things, the specialty of the physician who initiated glucocorticoids and the adjuvant measures they were prescribed at treatment initiation. RESULTS: In all, 1383 patients answered the questionnaire and 843 (61%) questionnaires were analyzed (women: 70.6%, median age: 59 [44-70] years, current glucocorticoid dosage: 12.5 [5-30] mg/day, maximum dose: 42 [20-60] mg/day). The main prescribers were rheumatologists (30.5%) and internists (17.3%). Most adjuvant measures were heterogeneously prescribed and depended largely on the specialty of the prescribing physician. Some probably unnecessary measures in most patients (potassium supplementation, prevention of peptic ulcer, low-sodium diet) were frequently prescribed while other consensual measures (prevention of osteoporosis, vaccinations) were prescribed to less than half of patients. In multivariable analyses, most of the studied measures were more frequently prescribed by internists than by colleagues of other specialties. Pneumologists more often vaccinated patients against influenza or pneumococcus than their colleagues. CONCLUSION: Adjuvant measures to long-term glucocorticoid therapy are heterogeneously prescribed. The prescriptions depend largely on the medical specialty of the prescribing physician.

Long-term neuropathy and quality of life in colorectal cancer patients treated with oxaliplatin containing adjuvant chemotherapy.

BACKGROUND: Oxaliplatin, combined with capecitabine (CAPOX) or infused 5-fluorouracil (FOLFOX), is standard of care in the adjuvant treatment of colorectal cancer (CRC). Prospective data on prevalence of oxaliplatin induced acute and long-term neuropathy in a real-life patient population and its effects on quality of life (QOL) and survival is limited, and scarce in CAPOX versus FOLFOX treated, especially in a subarctic climate. METHODS: One hundred forty-four adjuvant CRC patients (all 72 CAPOX cases and 72 matched FOLFOX controls) were analyzed regarding oxaliplatin induced sensory neuropathy, which was graded according to NCI-CTCAEv3.0. Ninety-two long-term survivors responded to the QOL (EORTC QLQ-C30) and Chemotherapy-Induced Peripheral Neuropathy (EORTC CIPN20) questionnaires and were interviewed regarding long-term neuropathy. RESULTS: Acute neurotoxicity was present in 94% (136/144) during adjuvant therapy and there was a significant association between acute neurotoxicity and long-term neuropathy (p < .001). Long-term neuropathy was present in 69% (grade 1/2/3/4 in 36/24/8/1%) at median 4.2 years. Neuropathy grades 2-4 did not influence global health status, but it was associated with decreased physical functioning (p = .031), decreased role functioning (p = .040), and more diarrhea (p = .021) in QLQ-C30 items. There were no differences in acute neurotoxicity, long-term neuropathy, or in QOL between CAPOX and FOLFOX treated. Neuropathy showed no pattern of variation according to starting and stopping month or treatment during winter. CONCLUSIONS: Neuropathy following oxaliplatin containing adjuvant chemotherapy is present in two-thirds, years after cessation, and impairs some QOL scales. There is no difference in severity of acute or long-term neuropathy between CAPOX and FOLFOX treated and QOL is similar. No seasonal variation in neuropathy was noted.

Toxicity-induced modification of treatment: what is in a name?

Severe treatment-induced toxicities can have clinical consequences such as hospitalisation or treatment modifications, which in turn may deteriorate the prognosis of patients with cancer. Identification of determinants of treatment-induced toxicities is essential to develop strategies that promote therapy compliance and enhance the quality of life. Whereas toxicities are systematically recorded and graded per protocol in most clinical trials, observational studies often depend on retrospective data collection from medical records collected as standard care. Existing population-based or patient cohorts are a valuable source of information, even when relying on retrospective data collection, but comparisons across studies are hampered by a lack of a uniform definition for toxicity outcomes. We propose a new standardised approach to summarise toxicities in observational studies that rely on medical records for outcome assessment. We recommend the term 'toxicity-induced modification of treatment' (TIMT) to cover all toxicities that are responsible for changes in a planned treatment schedule. We define a TIMT as (i) a dose reduction, (ii) temporary interruption, (iii) discontinuation of therapy or (iv) an unanticipated switch to another regimen, as a result of treatment-induced toxicities and not because of progressive disease. This definition will provide clinically relevant information, especially when data on specific adverse events and Common Terminology Criteria for Adverse Events (CTCAE) grades are not uniformly available. Implementation of this definition empowers comparisons across studies, facilitates communication between clinicians and researchers and will allow new research questions in this active field of research.

"Errar es humano. Ocultar los errores es imperdonable. No aprender de ellos no tiene justificación" / "To err is human. To cover up is unforgivable. To fail to learn is inexcusable."

Es muy frecuente que cuando nos encontramos en frente de nuestros pacientes, colegas, alumnos o simplemente cuando estamos recopilando resultados de nuestras observaciones para escribir un artículo científico, al momento de tener en cuenta los efectos adversos o las complicaciones que se presentan sintamos preocupación y se generen diferentes sentimientos de frustración. A la luz de la práctica médica actual, y en especial de la Cardiología y la Cirugía Cardiovascular, foco temático de esta Revista Colombiana de Cardiología, cada día nos enfrentamos a pacientes más complejos, prematuros o ancianos, con multimorbilidades (diabetes, enfermedades mentales, pulmonares, renales, hepáticas, fragilidad, etc.), polifarmacia (diuréticos, vasodilatadores, anticoagulantes, inhibidores de bomba de protones, anti-arrítmicos, analgésicos, etc.), re-intervenidos varias veces y sometidos a intervenciones percutáneas diversas (marcapasos, desfibriladores, stents, válvulas percutáneas, implante de MitraClips, cierre de apéndice auricular izquierdo, endoprótesis de aorta, cierres percutáneos de defectos intracardiacos, etc.), cirugías de revascularización miocárdica, y muchos más, y el uso de nuevos medicamentos, dietas, productos homeopáticos que salen al mercado para el tratamiento y control de condiciones especiales, incrementando la posibilidad de eventos adversos y iatrogenia, que además ponen en riesgo la salud del paciente y su la vida, aumentando los tiempos de hospitalización y los reingresos y, finalmente, los costos al sistema de salud.

Perineal Stapled Rectal Prolapse Resection in Elderly Patients: Long-term Follow-up.

BACKGROUND: Full-thickness rectal prolapse has a significant negative impact on quality of life. The therapeutic options, specifically in elderly patients, are imperfect. Perineal stapled rectal prolapse resection is a novel operation for treating external rectal prolapse. Long-term follow-up following this procedure is lacking. In our study, we report a long-term follow-up of 30 patients, analyzing the long-term recurrence rate, morbidity, and functional outcome. OBJECTIVE: This study aimed to examine the long-term results of perineal stapled rectal resection in a population unfit for prolonged general anesthesia. DESIGN: This was a cohort study with a prospective follow-up. SETTINGS: This study was conducted at a single tertiary referral center. PATIENTS: Patients undergoing perineal stapled rectal resection from January 2010 to June 2013 were included. INTERVENTIONS: Perineal stapled rectal prolapse resection was performed. MAIN OUTCOME MEASURES: The primary outcome measured was prolapse recurrence. RESULTS: A total of 30 patients underwent the surgical intervention. The median follow-up period was 61 months (range, 37-65). No intraoperative or postoperative complications occurred. Six patients (20%) had recurrent rectal prolapse, and continence was not achieved in any of the patients. Two patients who had recurrence underwent a redo perineal stapled rectal resection. LIMITATIONS: This study was limited by the small cohort of selected patients. CONCLUSIONS: Frail patients that can only endure a short procedure under regional anesthesia should be considered for perineal stapled rectal prolapse resection. The lack of mortality and morbidity, specifically in this population, along with the low long-term recurrence rates, make this a favorable surgical alternative. See Video Abstract at http://links.lww.com/DCR/A745.

Long-term outcomes of a Malone antegrade continence enema (MACE) for the treatment of fecal incontinence or constipation in adults.

PURPOSE: The aim of the study was to assess the long-term outcome of a Malone antegrade continence enema (MACE) procedure for fecal incontinence or constipation in adults. METHODS: This retrospective single-center study assessed the long-term outcome and quality of life (QoL) of patients who underwent a MACE procedure between 2005 and 2014 at the Maastricht University Medical Centre. Success rate was quantified by using Malone's continence scale. Quality of life was assessed by validated questionnaires covering general quality of life (SF-36 and Karnofsky scale), current pain level (visual analog scale), fecal incontinence (Vaizey incontinence survey), or constipation (Cleveland Clinic Constipation Score). RESULTS: Based on patients' records, 22 out of 30 patients (73%; 95% CI 54-87%) were still using their MACE. Mean follow-up was 43 months (SD 25.9) since time of surgery. According to the Malone continence scale, the overall success rate was 37% (95% CI 20.0-53.3). Nine patients developed a postoperative complication. Eighteen out of 22 patients (13 with constipation and 5 with fecal incontinence) returned the QoL questionnaires (82% response rate). Long-term quality of life of patients with a MACE did not differ from the general Dutch population. CONCLUSIONS: In our cohort of patients with fecal incontinence or constipation, MACE resulted in a disappointed overall success rate of 37%. However, it may be indicated in patients who do not prefer more invasive surgical procedures or a definite stoma. The success and morbidity rate should be thoroughly discussed with the patients preoperatively.

Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes.

Importance: In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors. Objective: To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations. Design, Setting, and Participants: In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation. Exposures: Chemotherapy agents known to be toxic to peripheral nerves. Main Outcomes and Measures: The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures. Results: Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion. Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 53 of 100 participants (53.0%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 µV; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient-reported outcomes demonstrating reduction in global quality of life and physical functioning were associated with the Total Neuropathy Score. Cisplatin produced long-term neurotoxicity more frequently than vinca alkaloids. Conclusions and Relevance: Clinical abnormalities attributable to peripheral neuropathy were common in childhood cancer survivors and persisted long term, with concurrent deficits in patient-reported outcomes. Both the type of neurotoxic agent and a targeted clinical neurological assessment are important considerations when screening survivors for long-term neuropathy. Further development of peripheral neuropathy-specific pediatric assessment tools will aid research into neuroprotective and rehabilitative strategies.

Long-term Impact of Oral Azithromycin Taken by Gambian Women During Labor on Prevalence and Antibiotic Susceptibility of Streptococcus pneumoniae and Staphylococcus aureus in Their Infants: Follow-up of a Randomized Clinical Trial.

Background: Oral azithromycin given to women in labor decreases maternal and neonatal bacterial carriage but increases azithromycin-resistant bacteria during at least 4 weeks following the intervention. We assessed the prevalence of bacterial carriage and azithromycin resistance 12 months after treatment among study infants. Methods: Nasopharyngeal swabs (NPSs) were collected between November 2014 and May 2015 from children aged 11-13 months whose mothers had received azithromycin or placebo during labor. Streptococcus pneumoniae and Staphylococcus aureus were isolated using conventional microbiological methods. Antibiotic susceptibility was determined by disk diffusion and confirmed by Etest or VITEK-2. Results: NPSs were collected from 461 children. The prevalence of S. pneumoniae and S. aureus was similar between children from the azithromycin and placebo arms (85.0% vs 82.1%; odds ratio [OR], 1.23 [95% confidence interval {CI}, .73-2.08] for S. pneumoniae and 21.7% vs 21.3%; OR, 1.02 [95% CI, .64-1.64] for S. aureus). Prevalence of azithromycin-resistant S. pneumoniae was similar in both arms (1.8% vs 0.9% in children from the azithromycin and placebo arms, respectively; OR, 2.10 [95% CI, .30-23.38]); resistance to other antibiotics was also similar between arms. For S. aureus, there was no difference in azithromycin resistance between children in the azithromycin (3.1%) and placebo (2.6%) arms (OR, 1.22 [95% CI, .35-4.47]) or resistance to any other antibiotics. Conclusions: The higher prevalence of S. aureus azithromycin resistance observed among women treated during labor and their babies 4 weeks after treatment had waned 12 months after delivery. Azithromycin intervention did not induce other antibiotic resistance to S. pneumoniae or S. aureus. Clinical Trials Registration: NCT01800942.

Late cure of focal ventricular arrhythmias post-catheter ablation: electrophysiological characteristics and long-term outcome.

PURPOSE: Late cure after a previously failed ablation of ventricular arrhythmias (VAs) is a relatively common phenomenon. The present study sought to delineate the incidence and electrophysiological characteristics of late cure in idiopathic VA patients. METHODS: Totally, 45 idiopathic VA cases (mean age 44 ± 18 years, 27 males) either failed acutely or recurred within 12 h were enrolled in this study. Based on intensive clinical observations in the acute period, 19 (42%) patients demonstrated late cure in the first week after the procedure. RESULTS: The late cure patients had significantly better acute and cumulative ablation effects during the procedure than did those without a late cure. Additionally, they had a prediction that originated from the right ventricular outflow tract, aortic-mitral continuum, and left summit area relative to other sites (13/18 vs 6/27, p < 0.01). In a median follow-up of 24 [14, 46] months, 7/19 (37%) patients had their VAs recurred. The late cure group had significantly more patients cured at long-term follow-up than those without (12/19 vs 0/26, p < 0.01). A cutoff value of the "time to eliminate VAs" > 7.0 s was able to predict a long-term recurrence of the VAs with 62.5% sensitivity and 85.7% specificity. CONCLUSIONS: The late cure of VAs occurs in more than one third of patients who have a seemingly unsuccessful ablation session, which is clustered in the first week after the procedure. However, long-term recurrence of VAs occurred in 37% of the late cure patients, emphasizing the importance of long-term follow-up.

[Results of administering oral anticoagulants for treatment of patients with venous thromboembolic complications]. / Rezul'taty primeneniia peroral'nykh antikoaguliantov pri lechenii bol'nykh s venoznymi tromboémbolicheskimi oslozhneniiami.

The objective of the study was to compare safety and efficacy of rivaroxaban and dabigatran with warfarin in treatment of patients with acute venous thromboembolic complications (VTEC). The authors analysed the results of examining and treating a total of 95 patients presenting with VTEC and randomly divided into three groups. In all groups the initial anticoagulant therapy consisted in unfractionated heparin administered for 5 days, after which the patients followed by switching were switched to a 6-month course of treatment with oral anticoagulants. Patients from Group One received warfarin, Group Two patients were treated with dabigatran etexilate, and Group Three patients were treated with rivaroxaban. Relapses of the disease were diagnosed in 2 (5.7%) patients from Group One. Haemorrhagic complications were noted in 8 (22.9%) Group One patients, in 3 (10%) Group Two patients and in 2 (6.7%) Group Three patients. After the end of treatment, complete recanalization of the thrombosed veins was revealed 13 (37.1%) patients from Group One, in 15 (50%) patients from Group Two and in 14 (46.7%) patients from Group Three. One year after the end of treatment, freedom from chronic venous insufficiency was observed in 8 (23.3%) patients of Group One, in 12 (40%) patients of Group Two and in 11 (36.6%) patients of Group Three. The composite quality of life indices after the treatment course were (appeared to be) higher in Group Two and Three patients compared with those of Group One. Hence, a conclusion was drawn that dabigatran and rivaroxaban turned out to be superior by efficacy and safety to warfarin in treatment of this patient cohort. No statistically significant differences were observed while comparing dabigatran and rivaroxaban.

Ventricular Late Potentials Immediately Post ST-Elevation Myocardial Infarction, and Very Long-Term Mortality.

BACKGROUND: The very long-term prognostic significance of ventricular late potentials (VLP) in patients post ST-elevation myocardial infarction (STEMI) is unclear. OBJECTIVES: To evaluate the long-term predictive value of VLP for mortality post-STEMI. METHODS: We conducted serial signal-averaged electrocardiography (SAECG) measurements in 63 patients on the 1st, 2nd and 3rd day pre-discharge, and 30 days after STEMI in patients admitted in 2001. We followed the patients for 10 years and correlated the presence of VLP with all-cause and cardiovascular mortality. RESULTS: The mean age was 59.9 ± 12.3 years. Thrombolysis was performed in 41 patients (65%). Percutaneous coronary intervention was performed pre-discharge in 40 patients (63%) and coronary artery bypass grafting in 7 (11%). Five consecutive measurements to define the presence of VLP were obtained in 52 patients (21 with VLP and 31 without). We found a higher prevalence of VLP in males compared to females (QRS segment > 114 msec, 51% vs. 12%, P = 0.02, duration of the low amplitude signal < 40 mV) in the terminal portion of the averaged QRS complex > 38 msec, 47% vs. 25%, P = 0.05). Over 10 years of follow-up, 14 (22%) patients died, 10 (70%) due to cardiovascular non-arrhythmic complications, 6 with VLP compared to only 3 without (28.6% vs. 9.7%, P = 0.125, hazard ratio = 2.96, confidence intervals = 0.74-11.84) (are these numbers meant to total 10?). CONCLUSIONS: Over 10 years of follow-up, the presence of VLP in early post-STEMI is not predictive of arrhythmic or non-arrhythmic cardiovascular mortality.