Project description:BackgroundRadiotherapy (RT) of ependymoma in children is an important part of the interdisciplinary treatment concept. However, feasibility and dose concepts are still under investigation, particularly in very young children. The aim of this study was to evaluate the standard dose and volume of proton therapy (PT) in children with ependymoma.MethodsIn this analysis, 105 patients with localized, intracranial ependymoma under the age of 18 years treated with PT between 2013 and 2018 were included. Patient characteristics, treatment, outcome, and follow-up data were analyzed using descriptive statistics, Kaplan-Meier, and Cox regression analysis.ResultsThe median age of patients at PT was 2.8 years (0.9-17.0 years). The molecular subgroup analysis was performed in a subset of 50 patients (37 EP-PFA, 2 EP-PFB, 7 EP-RELA, 2 EP-YAP, 2 NEC [not elsewhere classified]). The median total dose was 59.4 Gy (54.0-62.0 Gy). The median follow-up time was 1.9 years. The estimated 3-year overall survival (OS), local control (LC), and progression-free survival (PFS) rates were 93.7%, 74.1%, and 55.6%, respectively. Within univariable analysis, female gender and lower dose had a positive impact on OS, whereas age ≥4 years had a negative impact on OS and PT given after progression had a negative impact on PFS. In the multivariable analysis, multiple tumor surgeries were associated with lower PFS. New ≥3° late toxicities occurred in 11 patients.ConclusionFor children with localized ependymoma, PT was effective and well tolerable. Multiple surgeries showed a negative impact on PFS.
Project description:BackgroundCommunity acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20-29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts.MethodsPROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments.DiscussionWith the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility.Trial registrationThe PROGRESS study was retrospectively registered on May 24(th), 2016 with ClinicalTrials.gov: NCT02782013.
Project description:BackgroundPneumonia is one of the leading causes of morbidity and mortality in under fives. We carried out a comprehensive study to identify factors influencing both mortality and morbidity for children less than 5 years of age hospitalized with severe pneumonia.Methods200 hospitalized children aged 2-60 months with World Health Organization (WHO) defined severe pneumonia were enrolled in the study. The children were managed using a standard protocol. They were closely followed up for need for change in antibiotics, prolonged hospital stay, need for mechanical ventilation and mortality. Data on the factors influencing the outcome were collected.ResultsOf 200 children enrolled in the study, 113 (56.5%) needed a change in antibiotics, 102 (51%) stayed for more than 5 days in the hospital, 41 (20.5%) needed mechanical ventilation and 21 (10.5%) died. On multivariate analysis, lack of exclusive breastfeeding [RR (95%CI) 2.63 (2.16-2.86)], overcrowding [RR (95%CI) 1.94 (1.35-2.38)] and an abnormal chest x-ray [RR (95%CI) 2.29 (1.22-3.44)] were associated with the need for change of antibiotics. Lack of exclusive breastfeeding [RR (95%CI) 2.56 (2.0-2.93)], overcrowding [RR (95%CI) 2.59 (1.78-3.23)] and an abnormal chest x-ray [RR (95%CI) 2.99 (1.65-4.38)] were identified as determinants for prolonged hospital stay. Head nodding [RR (95%CI) 8.34 (2.71-12.77)], altered sensorium [RR (95%CI) 5.44 (1.34-17.56)], abnormal leukocyte counts [RR (95%CI) 5.85(1.36-17.14)] and pallor [RR (95%C) 10.88 (2.95-20.40)] were associated with mortality. Head nodding (RR (95% CI) 4.73 (1.50-6.36)] and cyanosis (RR (95%CI) 5.06 (1.80-11.34)] were the determining factors for mechanical ventilation. In radiographically confirmed pneumonia, the determining factors for change of antibiotics were: lack of exclusive breast feeding [RR (95% CI) 2.05 (1.69-2.2)] and low birth weight [RR (95% CI) 1.59 (1.1-1.89)]. For prolonged hospital stay, the factors identified were mothers' education less than graduation [RR (95% CI) 1.5 (1.19-1.7)], lack of exclusive breast feeding [RR (95% CI) 1.77 (1.19-2.09)] and oxygen saturation of < 90% at time of presentation [RR (95% CI) 2.06 (1.42-2.42)]. Determinants for mechanical ventilation were mothers' education less than graduation [RR (95% CI) 3.6 (1.15-6.3)] and cyanosis at presentation [RR (95% CI) 10.9 (1.56-18.9)]. For mortality, the only determinant was pallor [RR (95% CI) 10.54 (1.8-21.79)].ConclusionChildren hospitalized with severe community acquired pneumonia [as defined by World Health Organization (WHO)] who had not received exclusive breast feeding, had stayed in an overcrowded homes and had an abnormal chest radiograph were more likely to fail to respond with primary antibiotic regimen and require change of antibiotics and prolonged hospital stay. In children with radiographically confirmed pneumonia, lack of breast feeding and low birth weight was associated with need for change in antibiotics.
Project description:INTRODUCTION:The importance of alcohol co-ingestion for outcome in organophosphorus (OP) insecticide self-poisoning has only been studied for the relatively hydrophilic dimethyl insecticide, dimethoate. We aimed to assess the effect of alcohol in acute poisoning with the lipophilic S-alkyl OP insecticide, profenofos. METHODOLOGY:Demographic and clinical data, including an alcohol history, were prospectively collected from all cases of acute poisoning with agricultural profenofos EC50 presenting to two Sri Lankan hospitals over seven years. RESULTS:Of 1859 patients with acute OP insecticide self-poisoning, 243 (13.1%) reported ingestion of profenofos (male 182/243, 74.9%). Alcohol co-ingestion was reported by 64/243 (26.3%). All patients reporting alcohol co-ingestion were male (64/64 [100%] vs 118/179 [65.9%] not reporting alcohol ingestion, p<0.001). More patients reporting alcohol co-ingestion died (10/64 [15.6%] vs 10/179 [5.6%]; p = 0.013) and required intubation (13/64 [20.3%] vs 16/179 [8.9%], p = 0.016) compared to those who did not co-ingest alcohol. Using multi-logistic regression, controlling for the estimated dose ingested, age (OR 11.1 [2.5 to 48.9] for age > 35 years vs ?35 years) and alcohol co-ingestion (OR 3.1 [1.2 to 7.9]) were independently associated with increased risk of death. Increased risk of intubation was independently associated with age (OR 3.2 [1.6 to 6.6] for age > 35 years vs ?35 years) and alcohol co-ingestion (OR 3.2 [1.6 to 6.4]). CONCLUSION:A history of alcohol co-ingestion, as well as older age, is independently associated with worse outcome in patients' self-poisoned with profenofos.
Project description:Background and purposeEmbryonal tumors with multilayered rosettes (ETMRs) are aggressive tumors that typically occur in young children. Radiation is often deferred or delayed for these patients due to late effects; proton therapy may mitigate some of these concerns. This study reviews the role of radiation in ETMR and describes initial results with proton therapy.Materials and methodsRecords of patients with embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma (MEP), and ependymoblastoma (EPL) treated with proton therapy at our institution were retrospectively reviewed. A literature review of cases of CNS ETANTR, MEP, and EPL published since 1990 was also conducted.ResultsSeven patients were treated with proton therapy. Their median age at diagnosis was 33 months (range 10-57 months) and their median age at radiation start was 42 months (range 17-58 months). Their median overall survival (OS) was 16 months (range 8-64 months), with three patients surviving 36 months or longer. Five patients had disease progression prior to starting radiation; all 5 of these patients failed in the tumor bed. A search of the literature identified 204 cases of ETMR with a median OS of 10 months (range 0.03-161 months). Median OS of 18 long-term survivors (≥36 months) in the literature was 77 months (range 37-184 months). Of these 18 long-term survivors, 17 (94%) received radiotherapy as part of their initial treatment; 14 of them were treated with craniospinal irradiation.ConclusionsOutcomes of patients with ETMR treated with proton therapy are encouraging compared to historical results. Further study of this rare tumor is warranted to better define the role of radiotherapy.
Project description:Metaplastic breast cancer is a rare and often chemo-refractory subtype of breast cancer with poor prognosis and limited treatment options. Recent studies have reported overexpression of programmed death ligand 1 (PD-L1) in metaplastic breast cancers, and there are several reports of anti-PD-1/L1 being potentially active in this disease. In this case series, we present 5 patients with metastatic metaplastic breast cancer treated with anti-PD-1-based therapy at a single center, with 3 of 5 cases demonstrating a response to therapy, and one of the responding cases being a metaplastic lobular carcinoma with low-level hormone receptor expression. Cases were evaluated for PD-L1 expression, tumor infiltrating lymphocytes (TILs), DNA mutations, RNA sequencing, and T-cell receptor sequencing. Duration of the response in these cases was limited, in contrast to the more durable responses noted in other recently published reports.
Project description:BackgroundResults of randomized controlled trials (RCT) do not provide definite guidance for secondary prevention after ischemic stroke (IS)/transient ischemic attack (TIA) attributed to patent foramen ovale (PFO). No recommendations can be made for patients > 60 years. We aimed to compare interventional and medical PFO-management in cryptogenic IS/TIA patients, including patients > 60 years.MethodsProspective case series including consecutive cryptogenic IS/TIA patients with PFO at Tuebingen university stroke unit, Germany. 'PFO-closure' was recommended in patients ≤70 years when featuring high-risk PFO (i.e., with atrial septal aneurysm, spontaneous, or high-grade right-to-left shunt during Valsalva). Primary (recurrent IS/intracranial hemorrhage) and secondary endpoints (e.g., disability) were assessed during ≥1-year follow-up; planned subgroup analyses of patients ≤60/> 60 years.ResultsAmong 236 patients with median age of 58 (range 18-88) years, 38.6% were females and median presenting National Institutes of Health Stroke Scale score was 1 (IQR 0-4). Mean follow-up was 2.8 ± 1.3 years. No intracranial hemorrhage was observed. Recurrent IS rate after 'PFO-closure' was 2.9% (95%CI 0-6.8%) and 7% (4-16.4) in high-risk PFO patients ≤60 (n = 103) and > 60 years (n = 43), respectively, versus 4% (0-11.5) during 'medical therapy alone' MTA (n = 28). 42 low-risk PFO patients treated with MTA experienced no recurrent IS/TIA.ConclusionsIn our real-world study, IS recurrence rate in 'PFO-closure' high-risk PFO patients ≤60 years was comparable to that observed in recent RCT. High-risk PFO patients > 60 years who underwent PFO-closure had similar IS recurrence rates than those who received MTA. MTA seems the appropriate treatment for low-risk PFO.Trial registrationClinicalTrials.gov, registration number: NCT04352790 , registered on: April 20, 2020 - retrospectively registered.
Project description:BackgroundPneumonia is the leading infection-related cause of death. The use of simple clinical criteria and contemporary epidemiology to identify patients at high risk of nosocomial pneumonia should enhance prevention efforts and facilitate development of new treatments in clinical trials.Research questionWhat are the clinical criteria and contemporary epidemiology trends that are helpful in the identification of patients at high risk of nosocomial pneumonia?Study design and methodsWithin the ICUs of 28 US hospitals, we conducted a prospective cohort study among adults who had been hospitalized >48 hours and were considered high risk for pneumonia (defined as treatment with invasive or noninvasive ventilatory support or high levels of supplemental oxygen). We estimated the proportion of high-risk patients who experienced the development of nosocomial pneumonia. Using multivariable logistic regression, we identified patient characteristics and treatment exposures that are associated with increased risk of pneumonia development during the ICU admission.ResultsBetween February 6, 2016, and October 7, 2016, 4,613 high-risk patients were enrolled. Among 1,464 high-risk patients (32%) who were treated for possible nosocomial pneumonia, 537 (37%) met the study pneumonia definition. Among high-risk patients, a multivariable logistic model was developed to identify key patient characteristics and treatment exposures that are associated with increased risk of nosocomial pneumonia development (c-statistic, 0.709; 95% CI, 0.686-0.731). Key factors associated with increased odds of nosocomial pneumonia included an admission diagnosis of trauma or cerebrovascular accident, receipt of enteral nutrition, documented aspiration risk, and receipt of systemic antibacterials within the preceding 90 days.InterpretationTreatment for nosocomial pneumonia is common among patients in the ICU who are receiving high levels of respiratory support, yet more than one-half of patients who are treated do not fulfill standard diagnostic criteria for pneumonia. Application of simple clinical criteria may improve the feasibility of clinical trials of pneumonia prevention and treatment by facilitating prospective identification of patients at highest risk.
Project description:BackgroundAbnormal movements in Covid-19 patients have been reported with varying degree of frequency, prompting neurologic consultation and additional diagnostic evaluation. We sought to evaluate the frequency and etiology of abnormal movements among hospitalized Covid-19 patients undergoing neurologic consultation.MethodsWe retrospectively analyzed the first 50 consecutive patients with confirmed Covid-19 hospitalized at our tertiary medical care center who underwent acute inpatient neurology consultation from March 2020 through May 2020. Indication for neurologic consultation and diagnostic studies performed were identified by electronic medical record review.ResultsOf the 50 initial consultation requests, 11 (22.0%) patients were evaluated for abnormal movements (nine male and two female). Myoclonus was diagnosed in 6/11 (54.5%) patients. Additionally, two patients were diagnosed with seizures (confirmed on EEG in one), while two additional patients were diagnosed with tremor (physiologic and probable functional). A single case of serotonin syndrome was also identified.ConclusionAbnormal movements observed in hospitalized Covid-19 patients can have a wide range of etiologies and were a frequent initial indication for neurologic consultation. Myoclonus was the most frequent type of abnormal movement observed. Early clinical recognition and directed diagnostic work-up is essential for accurate diagnoses in these patients.
Project description:Hypertriglyceridemia is an independent risk factor of coronary heart disease (as established through various previously conducted studies) and it's rising incidence is creating a need for the immediate attention of it's management. Instead of focusing on the controversies involving the toxicity caused due to the long-term use of statin therapy in conventional mode of treatment, opting for a safer alternative system of treatment seems important. Five cases of diagnosed HTG, with triglyceride levels above 200 were treated with homoeopathic medicine - Fucus vesiculosus, in mother tincture form. The primary outcome measure was to evaluate the reduction in the blood triglyceride levels. All the five cases showed a reduction in triglyceride levels to normal range within 4 months of starting the treatment with the Fucus vesiculosus mother tincture. Also, it was observed that the borderline cholesterol levels and high LDL levels in 2 cases were found to reduce to normal. Treatment involving Fucus vesiculosus in cases diagnosed with HTG showed significant reduction in triglyceride levels along with other parameters of lipid profile. Further authentication of results with significant sample sizes may be taken up.