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Background. Approximately 15 700 invasive methicillin-resistant Staphylococcus aureus (MRSA) infections occurred in US dialysis patients in 2010. Frequent hospital visits and prolonged bloodstream access, especially via central venous catheters (CVCs), are risk factors among hemodialysis patients. We describe the epidemiology of and recent trends in invasive MRSA infections among dialysis patients. Methods. We analyzed population-based data from 9 US metropolitan areas from 2005 to 2011. Cases were defined as MRSA isolated from a normally sterile body site in a surveillance area resident who received dialysis, and were classified as hospital-onset (HO; culture collected >3 days after hospital admission) or healthcare-associated community-onset (HACO; all others). Incidence was calculated using denominators from the US Renal Data System. Temporal trends in incidence and national estimates were calculated controlling for age, sex, and race. Results. From 2005 to 2011, 7489 cases were identified; 85.7% were HACO infections, and 93.2% were blood-stream infections. Incidence of invasive MRSA infections decreased from 6.5 to 4.2 per 100 dialysis patients (annual decrease, 7.3%) with annual decreases of 6.7% for HACO and 10.5% for HO cases. Among cases identified during 2009–2011, 70% of patients were hospitalized in the year prior to infection. Among hemodialysis cases, 60.4% of patients were dialyzed through a CVC. The 2011 national estimated number of MRSA infections was 15 169. Conclusions. There has been a substantial decrease in invasive MRSA infection incidence among dialysis patients. Most cases had previous hospitalizations, suggesting that efforts to control MRSA in hospitals might have contributed to the declines. Infection prevention measures should include improved vascular access and CVC care.

Nucleic acid amplification testing (NAAT) is increasingly being adopted for diagnosis of Clostridium difficile infection (CDI). Data from 3 states conducting population-based CDI surveillance showed increases ranging from 43% to 67% in CDI incidence attributable to changing from toxin enzyme immunoassays to NAAT. CDI surveillance requires adjustment for testing methods.

Background: This retrospective study aimed to identify prognostic factors in patients with brain metastases from cutaneous melanoma. Methods: In all, 265 patients under regular screening according to valid national surveillance guidelines were included in the study. Kaplan–Meier analyses were performed to estimate and to compare overall survival. Cox modeling was used to identify independent determinants of the overall survival, which were used in explorative classification and regression tree analysis to define meaningful prognostic groups. Results: In total, 55.5% of our patients presented with two or less brain metastases, 82.6% had concurrent extracranial metastasis and 64% were asymptomatic and diagnosed during surveillance scans. In all, 36.7% were candidates for local treatment (neurosurgery or stereotactic radiosurgery (SRS)). The median overall survival of the entire collective was 5.0 months (95% confidence interval: 4.3–5.7). Favourable independent prognostic factors were: normal pre-treatment level of serum lactate dehydrogenase ( P <0.001), administered therapy (neurosurgery or SRS vs other, P =0.002), number of brain metastases (single vs multiple, P =0.032) and presence of bone metastasis (false vs true, P =0.044). Three prognostic groups with significantly different overall survival were identified. Candidates for local treatment (group I) had the longer median survival (9 months). Remaining patients could be further classified in two groups on the basis of serum lactate dehydrogenase. Conclusion: Applied treatment and serum lactate dehydrogenase levels were independent predictors of survival of patients with brain metastases from cutaneous melanoma. Patients receiving local therapy have overall survival comparable with general stage IV melanoma patients.

The therapeutic efficacy of humanized or chimeric second-generation antitumor antibodies is clearly established, but often limited. In recent years, defined modifications of the glycosylation pattern or the amino-acid sequence of the human immunoglobulin G1 Fc part have resulted in the development of third-generation antibodies with improved capability to recruit Fc receptor-bearing effector cells. The first antibodies of this kind, currently evaluated in early clinical trials, are directed against lymphoma-associated antigens. Fc-engineered antibodies targeting myeloid leukemia are not yet available. We here report on the generation and preclinical characterization of an Fc-optimized antibody directed to the FMS-related tyrosine kinase 3 (FLT3), an antigen expressed on the leukemic blasts of all investigated patients with acute myeloid leukemia (AML). This antibody, termed 4G8SDIEM, mediated markedly enhanced cellular cytotoxicity against FLT3-expressing cell lines as well as blasts of AML patients. FLT3 expression levels on AML cells varied between 300 and 4600 molecules/cell and, in most cases, were substantially higher than those detected on normal hematopoietic precursor cells and dendritic cells (approximately 300 molecules/cell). Antibody-mediated cytotoxicity against these normal cells was not detectable. 4G8SDIEM has been produced in pharmaceutical quality in a university-owned production unit and is currently used for the treatment of leukemia patients.

Falls are a common and serious problem after stroke, often leading to injuries, loss of independence, and increased health care usage. Functional balance, a primary risk factor for falls, is frequently impaired in individuals with hemiparetic gait impairments. Previous research with the iStride gait device (Moterum Technologies, Inc) showed that functional balance improved immediately following 4 weeks of treatment. However, the long-term retention of these effects remains unknown and could improve the management of balance and mobility impairments after stroke. This study aimed to determine the long-term functional balance effects of treatment with the gait device for individuals with hemiparetic gait impairments from stroke. Eighteen individuals with chronic stroke (9 male, 9 female, mean age 57 years, and 60 months post stroke) participated in twelve 30-minute treatment sessions with the gait device. During each treatment session, the device was worn on the less affected lower extremity during overground ambulation in the participant's home. All treatment and assessments were overseen by licensed physical therapists. Functional balance was evaluated using the Berg Balance Scale (BBS), the Timed Up and Go (TUG) test, and the Functional Gait Assessment (FGA) at baseline and 5 posttreatment follow-ups: 1 week, 1 month, 3 months, 6 months, and 12 months after treatment. Balance improvement was analyzed using repeated-measures ANOVA from baseline to each follow-up time frame, correlation analysis, comparison to each outcome's minimal detectable change (MDC) value, evaluation of fall risk classification changes, and subjective questionnaires. Participants retained statistically significant improvements on the BBS, TUG, and FGA compared with baseline at all posttreatment time frames (P<.05). All participants initially identified as being at risk for falls reduced their fall risk on at least one outcome during one or more follow-up assessments. At 12 months post treatment, the average improvement on all 3 outcomes remained above their respective MDC thresholds, demonstrated by a 5.9-point improvement on the BBS, a 4.9-second improvement on the TUG, and a 34.6% (3.8-point) improvement on the FGA. At least 72% of participants exceeded the MDC of BBS, at least 44% exceeded the MDC of TUG, and at least 66% exceeded the MDC of FGA at every posttreatment time point. Subjective questionnaire responses indicated that 88% of participants perceived functional balance improvement following treatment with the gait device. The findings of this study indicate that treatment with the gait device may result in long-term functional balance improvement for individuals with hemiparetic gait impairments from stroke. Larger, controlled studies are recommended to confirm these findings.

Clostridium difficile is an important cause of hospital-associated diarrhea. In this report from the CDC, the U.S. burden of C. difficile infection is estimated at nearly 500,000 cases and 30,000 deaths in 2011, with an increasing burden among nonhospitalized persons. Changes in the epidemiology of Clostridium difficile infections have occurred since the emergence of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain, which has been responsible for geographically dispersed hospital-associated outbreaks. 1 – 3 In the United States, hospitalizations for C. difficile infection among nonpregnant adults doubled from 2000 through 2010 and were projected to continue to increase in 2011 and 2012, especially as laboratories transition to more sensitive C. difficile assays, such as the nucleic acid amplification test (NAAT). 4 – 6 On the basis of data from U.S. death certificates, C. difficile infection is the leading cause of gastroenteritis-associated death . . .

During the COVID-19 pandemic, rehabilitation providers and consumers adopted telehealth practices at unprecedented rates. Multiple prepandemic studies demonstrate the feasibility and comparable efficacy between in-clinic and remote treatment for certain impairments caused by stroke, such as upper extremity weakness and impaired motor function. However, less guidance has been available regarding gait assessment and treatment. Despite this limitation, safe and effective gait treatment is fundamental to optimizing health and well-being after stroke and should be considered a treatment priority, including during the COVID-19 pandemic. This study explores the feasibility of using telehealth to deliver gait treatment using a wearable gait device, the iStride device, to stroke survivors during the 2020 pandemic. The gait device is used to treat hemiparetic gait impairments caused by stroke. The device alters the user's gait mechanics and creates a subtle destabilization of the nonparetic limb; therefore, supervision is required during its usage. Before the pandemic, treatment with the gait device had been provided in person to appropriate candidates using a combination of physical therapists and trained personnel. However, upon the emergence of the COVID-19 pandemic, in-person treatment was halted in adherence to pandemic guidelines. This study investigates the feasibility of 2 remote delivery treatment models with the gait device for stroke survivors. Participants were recruited during the first half of 2020 after the onset of the pandemic and included 5 individuals with chronic stroke (mean age 72 years; 84 months post stroke). Four participants were previous gait device users who transitioned to the telehealth delivery model to continue their gait treatment remotely. The fifth participant performed all study-related activities, from recruitment through follow-up, remotely. The protocol included virtual training for the at-home care partner, followed by 3 months of remote treatment with the gait device. Participants were instructed to wear gait sensors during all treatment activities. To assess feasibility, we monitored the safety of the remote treatment, compliance with protocol activities, acceptability of the telehealth treatment delivery, and preliminary efficacy of the gait treatment. Functional improvement was measured using the 10-Meter Walk Test, the Timed Up and Go Test, and the 6-Minute Walk Test, and quality of life was assessed using the Stroke-Specific Quality of Life Scale. No serious adverse events occurred, and participants rated high acceptance of the telehealth delivery. Protocol compliance averaged 95% of treatment sessions, 100% of assessments, and 85% of sensor usage during treatment. After 3 months of treatment, the average improvement in each functional outcome exceeded the minimal clinically important difference or minimal detectable change value. Remote treatment delivery with the gait device appeared feasible with care partner support. Gait treatment using telehealth may be useful to offset negative immobility impacts for those requiring or preferring remote care during the pandemic or otherwise. ClinicalTrials.gov NCT04434313; https://clinicaltrials.gov/ct2/show/NCT04434313.

Radiotherapy of tumours proximal to normal CNS structures is limited by the sensitivity of the normal tissue. Prior to the development of prophylactic strategies or treatment protocols a detailed understanding of the mechanisms of radiation induced CNS toxicity is mandatory. Histological analysis of irradiated CNS specimens defines possible target structures prior to a delineation of cellular and molecular mechanisms. Several lesions can be distinguished: Demyelination, proliferative and degenerative glial reactions, endothelial cell loss and capillary occlusion. All changes are likely to result from complex alterations within several functional CNS compartments. Thus, a single mechanism responsible cannot be separated. At least four factors contribute to the development of CNS toxicity: (1) damage to vessel structures; (2) deletion of oligodendrocyte-2 astrocyte progenitors (O-2A) and mature oligodendrocytes; (3) deletion of neural stem cell populations in the hippocampus, cerebellum and cortex; (4) generalized alterations of cytokine expression. Several underlying cellular and molecular mechanisms involved in radiation induced CNS toxicity have been identified. The article reviews the currently available data on the cellular and molecular basis of radiation induced CNS side effects. © 2001 Cancer Research Campaign http://www.bjcancer.com

Background and purpose Palliative radiotherapy (RT) is routinely used in end of life care of patients with advanced malignancies; however, unnecessarily burdensome treatment shortly before death should be avoided. There is little knowledge on incidence and causes of intercurrent deaths during palliative RT. Patients and methods In this study death events among inpatients receiving palliative RT between January 2009 and December 2011 at this department were retrospectively analyzed. Among epidemiological factors, treatment schedule and chronology, latency and duration of treatment in relation to the actual survival were identified. Results In this study 52 patients died during or shortly after palliative RT. Symptomatic bone metastases and brain metastases represented the most common RT indications. The general health status was poor with a median Karnofsky performance score of 50 %, RT was realized with a median single dose of 2.5 Gy to a median total dose of 30.5 Gy and was stopped prematurely in 73 % of patients. On average 53 % of the remaining lifetime was occupied by latency to starting RT. Once RT was begun the treatment duration required a median 64 % of the still remaining lifetime. Conclusion The majority of patients who died had explicitly adverse pre-existing factors and rarely completed RT as scheduled. Latency to RT and RT duration occupied more than half of the remaining lifetime.

Background The purpose of the present study was to investigate outcome after whole brain radiotherapy (WBRT) alone as a palliative treatment without concomitant chemotherapy for intracranial leptomeningeal carcinomatosis (LMC). Patients and methods Overall survival and treatment response were retrospectively analyzed in 27 consecutive patients with LMC from breast and lung cancer. All patients had evidence of intracranial manifestations of LMC. Seven potential prognostic factors were evaluated. Results Median overall survival (OS) for the entire group was 8.1 weeks. OS rates after 6 and 12 months were 26% and 15%, respectively. Improvement of neurological deficits was observed in 3 patients. In 3 of 4 patients with follow-up MRI studies, a decreased size of contrast-enhanced lesions was observed. Prognostic factors for improved OS on univariate analysis were absence of cranial nerve dysfunction, Karnofsky Performance Score (KPS) > 60%, and time interval > 35 months between the initial diagnosis of malignant disease and development of LMC. On multivariate analysis, absence of cranial nerve dysfunction remained the only significant prognosticator for OS (median 3.7 vs. 19.4 weeks, p < 0.001). Conclusion WBRT alone is an effective palliative treatment for patients unfit/unsuitable for chemotherapy and low performance status suffering from intracranial LMC. However, prognostic factors should be considered in order to identify patients who are likely to benefit from WBRT.