nils-herrmann/clean_scirepeval huggingface dataset:
Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: immunological effects and clinical activity.

Mixed bacterial vaccine (MBV, Coley's toxins) is a historical, vaguely defined preparation of heat-inactivated Streptococcus pyogenes and Serratia marcescens used as nonspecific immunotherapy in the treatment of cancer. The mechanism of action is suspected to have an immunologic basis, yet it is poorly defined up to now. We developed a new, biochemically well defined and current good manufacturing practice-compliant MBV preparation, which has been investigated in patients with NY-ESO-1 expressing cancers.



Patients received MBV subcutaneously at a starting dose of 250 EU (endotoxin units) twice a week. The MBV dose was escalated in each patient until a body temperature of 38°C to 39.5°C was induced or up to the maximum dose of 547.000 EU. Changes in serum cytokine levels were determined and immune responses to NY-ESO-1 were evaluated. Tumor response was assessed according to RECIST.



Twelve patients were enrolled and 11 of them developed fever after the administration of MBV. Ten of 12 patients showed a consistent increase in serum IL-6 levels with the highest levels coinciding with the highest body temperature. A subgroup of patients showed increasing levels of TNF-α, IFN-γ, and IL1-β. A patient with metastatic bladder cancer showed a partial tumor response strongly correlated with MBV-induced fever and highly elevated levels of several cytokines.



MBV at fever-inducing dose levels can lead to a massive induction of immunoregulatory cytokines that may be involved in inducing tumor regressions. We propose to further explore the role of MBV as a potent immune modulator at higher dose levels and in conjunction with antigen-specific cancer vaccines.
Effects of ghrelin, growth hormone-releasing peptide-6, and growth hormone-releasing hormone on growth hormone, adrenocorticotropic hormone, and cortisol release in type 1 diabetes mellitus.

In type 1 diabetes mellitus (T1DM), growth hormone (GH) responses to provocative stimuli are normal or exaggerated, whereas the hypothalamic-pituitary-adrenal axis has been less studied. Ghrelin is a GH secretagogue that also increases adrenocorticotropic hormone (ACTH) and cortisol levels, similarly to GH-releasing peptide-6 (GHRP-6). Ghrelin's effects in patients with T1DM have not been evaluated. We therefore studied GH, ACTH, and cortisol responses to ghrelin and GHRP-6 in 9 patients with T1DM and 9 control subjects. The GH-releasing hormone (GHRH)-induced GH release was also evaluated. Mean fasting GH levels (micrograms per liter) were higher in T1DM (3.5 ± 1.2) than in controls (0.6 ± 0.3). In both groups, ghrelin-induced GH release was higher than that after GHRP-6 and GHRH. When analyzing Δ area under the curve (ΔAUC) GH values after ghrelin, GHRP-6, and GHRH, no significant differences were observed in T1DM compared with controls. There was a trend (P = .055) to higher mean basal cortisol values (micrograms per deciliter) in T1DM (11.7 ± 1.5) compared with controls (8.2 ± 0.8). No significant differences were seen in ΔAUC cortisol values in both groups after ghrelin and GHRP-6. Mean fasting ACTH values were similar in T1DM and controls. No differences were seen in ΔAUC ACTH levels in both groups after ghrelin and GHRP-6. In summary, patients with T1DM have normal GH responsiveness to ghrelin, GHRP-6, and GHRH. The ACTH and cortisol release after ghrelin and GHRP-6 is also similar to controls. Our results suggest that chronic hyperglycemia of T1DM does not interfere with GH-, ACTH-, and cortisol-releasing mechanisms stimulated by these peptides.
Effect of the dialysis fluid buffer on peritoneal membrane function in children.

Double-chamber peritoneal dialysis fluids exert less toxicity by their neutral pH and reduced glucose degradation product content. The role of the buffer compound (lactate and bicarbonate) has not been defined in humans.



A multicenter randomized controlled trial in 37 children on automated peritoneal dialysis was performed. After a 2-month run-in period with conventional peritoneal dialysis fluids, patients were randomized to neutral-pH, low-glucose degradation product peritoneal dialysis fluids with 35 mM lactate or 34 mM bicarbonate content. Clinical and biochemical monitoring was performed monthly, and peritoneal equilibration tests and 24-hour clearance studies were performed at 0, 3, 6, and 10 months.



No statistically significant difference in capillary blood pH, serum bicarbonate, or oral buffer supplementation emerged during the study. At baseline, peritoneal solute equilibration and clearance rates were similar. During the study, 4-hour dialysis to plasma ratio of creatinine tended to increase, and 24-hour dialytic creatinine and phosphate clearance increased with lactate peritoneal dialysis fluid but not with bicarbonate peritoneal dialysis fluid. Daily net ultrafiltration, which was similar at baseline (lactate fluid=5.4±2.6 ml/g glucose exposure, bicarbonate fluid=4.9±1.9 ml/g glucose exposure), decreased to 4.6±1.0 ml/g glucose exposure in the lactate peritoneal dialysis fluid group, whereas it increased to 5.1±1.7 ml/g glucose exposure in the bicarbonate content peritoneal dialysis fluid group (P=0.006 for interaction).



When using biocompatible peritoneal dialysis fluids, equally good acidosis control is achieved with lactate and bicarbonate buffers. Improved long-term preservation of peritoneal membrane function may, however, be achieved with bicarbonate-based peritoneal dialysis fluids.
Clinical application of the fast track surgery model based on preoperative nutritional risk screening in patients with esophageal cancer.

To investigate the clinical application of the fast track surgery (FTS) model based on preoperative nutritional risk screening (NRS) in patients with esophageal cancer.



180 patients with esophageal cancer who underwent surgery between January 2008 and April 2014 were randomly divided into study and control groups based on matched-pairs. The study group underwent assessment using the NRS 2002 and received treatment before surgery and the control group was treated by the conventional method. Postoperative indicators including time to first exsufflation, time to defecation, time to chest tube removal, hospitalization duration, and postoperative complications were examined after surgery.



Compared with the control group, the postoperative indicators including time to first exsufflation (88.4±2.76 vs 57.83±2.68 hours), time to first defecation (4.68±1.71 vs 3.28±1.34 days), time to chest tube removal (4.30±0.25 vs 2.70±0.33 days), postoperative hospitalization durations (11.71±1.39 vs 9.00±0.78 days), and total complication rate (18.9% [17/90] vs 6.67% [6/90]) were all significantly reduced in the study group (p<0.05).



The FTS model based on NRS can effectively promote postoperative rehabilitation of patients, reduce the incidence of postoperative complications, and shorten hospital stay.
Telemonitoring based service redesign for the management of uncontrolled hypertension: multicentre randomised controlled trial

To determine if an intervention consisting of telemonitoring and supervision by usual primary care clinicians of home self measured blood pressure and optional patient decision support leads to clinically important reductions in daytime systolic and diastolic ambulatory blood pressure in patients with uncontrolled blood pressure.



Multicentre randomised controlled trial.



20 primary care practices in south east Scotland.



401 people aged 29-95 years with uncontrolled blood pressure (mean daytime ambulatory measurement ≥ 135/85 mm Hg but ≤ 210/135 mm Hg).



Self measurement and transmission of blood pressure readings to a secure website for review by the attending nurse or doctor and participant, with optional automated patient decision support by text or email for six months.



Blinded assessment of mean daytime systolic ambulatory blood pressure six months after randomisation.



200 participants were randomised to the intervention and 201 to usual care; primary outcome data were available for 90% of participants (182 and 177, respectively). The mean difference in daytime systolic ambulatory blood pressure adjusted for baseline and minimisation factors between intervention and usual care was 4.3 mm Hg (95% confidence interval 2.0 to 6.5; P=0.0002) and for daytime diastolic ambulatory blood pressure was 2.3 mm Hg (0.9 to 3.6; P=0.001), with higher values in the usual care group. The intervention was associated with a mean increase of one general practitioner (95% confidence interval 0.5 to 1.6; P=0.0002) and 0.6 (0.1 to 1.0; P=0.01) practice nurse consultations during the course of the study.



Supported self monitoring by telemonitoring is an effective method for achieving clinically important reductions in blood pressure in patients with uncontrolled hypertension in primary care settings. However, it was associated with increase in use of National Health Service resources. Further research is required to determine if the reduction in blood pressure is maintained in the longer term and if the intervention is cost effective.
Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL).

Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure.



Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction < or =0.30 were enrolled in 2 clinical trials that differed only in the doses of etanercept used. In RECOVER, patients received placebo (n=373) or subcutaneous etanercept in doses of 25 mg every week (n=375) or 25 mg twice per week (n=375). In RENAISSANCE, patients received placebo (n=309), etanercept 25 mg twice per week (n=308), or etanercept 25 mg 3 times per week (n=308). The primary end point of each individual trial was clinical status at 24 weeks. Analysis of the effect of the 2 higher doses of etanercept on the combined outcome of death or hospitalization due to chronic heart failure from the 2 studies was also planned (RENEWAL). On the basis of prespecified stopping rules, both trials were terminated prematurely owing to lack of benefit. Etanercept had no effect on clinical status in RENAISSANCE (P=0.17) or RECOVER (P=0.34) and had no effect on the death or chronic heart failure hospitalization end point in RENEWAL (etanercept to placebo relative risk=1.1, 95% CI 0.91 to 1.33, P=0.33).



The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.
Tumor marker and measurement fluctuations may not reflect treatment efficacy in patients with medullary thyroid carcinoma on long-term RET inhibitor therapy.

RET kinase inhibitors have significant activity in patients with medullary thyroid carcinoma (MTC).



We retrospectively reviewed the electronic medical record for patterns of calcitonin, carcinoembryonic antigen (CEA) and tumor measurement responses in consecutive patients with MTC who received treatment with a RET inhibitor for at least 6 months.



Twenty-six patients who received RET kinase inhibitors for at least 6 months were included. All patients experienced an initial decline in calcitonin; 20 (77%) demonstrated later fluctuations in calcitonin, which spiked above baseline levels in 9 individuals (35%). Twenty of the 22 patients (91%) with elevated CEA experienced a decline with treatment, with 11 individuals (50%) later demonstrating transient fluctuations in CEA, including spikes above baseline in 7 patients (32%). Ten of the 26 patients (38%) also demonstrated short-lived fluctuations in RECIST measurements, including changes of over 20% from nadir values. Vacillations in calcitonin, CEA and measurements often occurred repeatedly in individual patients and did not regularly correlate with each other.



Repeated transient fluctuations in tumor markers and measurements are a characteristic of patients with MTC receiving treatment with RET inhibitors, and such short-term vacillations may not reflect responsiveness over the long term.
Extraoperative functional mapping of motor areas in epileptic patients by high-frequency cortical stimulation.

OBJECT
The aim of this study was to investigate the usefulness of a short train of high-frequency (500 Hz) cortical stimulation to delineate the primary motor cortex (MI), supplementary motor area (SMA), primary somatosensory cortex (SI), supplementary sensory area (SSA), negative motor area (NMA), and supplementary negative motor area (SNMA) in patients with epilepsy who were undergoing functional mapping.



Seventeen patients were studied, all of whom underwent functional mapping using 50-Hz electrical stimulation. After these clinical evaluations, cortical stimulations with a short train of electrical pulses at 500 Hz were performed through subdural electrodes placed at the MI, SMA, SI, SSA, NMA, and SNMA, which had been identified by 50-Hz stimulation, and surrounding cortical areas, while surface electromyography readings were recorded.



Stimulation of the MI elicited motor evoked potentials (MEPs) in contralateral muscles. Stimulation of the SMA also induced MEPs in contralateral muscles but with longer latencies compared with the MI stimulation. Stimulation of the SMA did not elicit MEPs in ipsilateral muscles. Stimulation of the SI, SSA, NMA, and SNMA did not induce MEPs in any muscle. In one patient, MEPs were elicited without seizure induction by 500-Hz stimulation of the electrodes, whereas a 50-Hz stimulation of the same electrodes induced his habitual seizures.



Extraoperative high-frequency stimulation with MEP monitoring is a useful complementary method for cortical mapping without inducing seizure. Stimulation of SMA induces MEPs in contralateral muscles, with longer latencies compared with the stimulation of MI. This finding may be useful for the differentiation between MI and SMA, especially in the foot motor areas.
Effect of ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation: patient-reported outcomes in the STRIVE randomized, controlled trial.

Cystic fibrosis (CF) is an inherited, rare autosomal recessive disease that results in chronically debilitating morbidities and high premature mortality. We evaluated how ivacaftor treatment affected CF symptoms, functioning, and well-being, as measured by the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a widely-used patient-reported outcome (PRO) measure.



STRIVE, a double-blind, placebo-controlled randomized trial, evaluated ivacaftor (150 mg) in CF patients aged 12+ with the G551D-CFTR mutation for 48 weeks. Treatment effect analysis used a mixed-effects repeated measures model. Treatment benefit analyses applied the cumulative distribution function and a categorical analysis of change scores ("improvement," "no change," or "decline"). Content-based interpretation examined treatment effect on specific item responses.



Data from 152 patients with a baseline CFQ-R assessment were analyzed. The treatment effect analysis favored treatment with ivacaftor over placebo on the Body Image, Eating, Health Perceptions, Physical Functioning, Respiratory, Social Functioning, Treatment Burden, and Vitality scales. Findings were supported by the analysis of categorical change. On all CFQ-R scales, the percentage of patients who improved was greater for ivacaftor. In the content-based analysis, the treatment benefit was characterized by better scores across a broad range of domains.



Results illustrate broad benefits of ivacaftor treatment across many domains: respiratory symptoms, physical and social functioning, health perceptions, and vitality, as measured by the CFQ-R. The breadth of improvements reflects the systemic mechanism of action of ivacaftor compared to other therapies. Findings support the patient-reported value of ivacaftor treatment in this patient population.
A Randomized Trial of Balloon Kyphoplasty and Nonsurgical Management for Treating Acute Vertebral Compression Fractures

Multicenter randomized controlled trial.



To compare the efficacy and safety of balloon kyphoplasty (BKP) with nonsurgical management (NSM) during 24 months in patients with painful vertebral compression fractures (VCFs).



Recently, several large randomized controlled trials have been conducted and reported how vertebral augmentation compares with NSM for patients with acute VCFs. Few of these trials report on the surgical aspects and radiographical vertebral deformity results.



Adults with 1 to 3 VCFs were randomized within 3 months of pain to undergo bilateral BKP (n = 149) or NSM (n = 151). Surgical parameters, subjective quality of life assessments and objective functional (timed up and go) and radiographical assessments were collected.



Compared with NSM, the BKP group had greater improvements in SF-36 physical component summary (PCS) scores at 1 month (5.35 points; 95% CI, 3.41-7.30; P < 0.0001) and when averaged across the 24 months (overall treatment effect 2.71 points; 95% CI, 1.34-4.09; P = 0.0001). The kyphoplasty group also had greater functionality by assessing timed up and go (overall treatment effect -2.49 s; 95% CI, -0.82 to -4.15; P = 0.0036). At 24 months, the change in index fracture kyphotic angulation was statistically significantly improved in the kyphoplasty group (average 3.13° of correction for kyphoplasty compared with 0.82° in the control, P = 0.003). Number of baseline prevalent fractures (P = 0.0003) and treatment assignment (P = 0.004) are the most predictive variables for PCS improvement; however, in patients who underwent BKP, there may also be a link with kyphotic angulation. In BKP, the highest quart for kyphotic angulation correction had higher PCS improvement (13.4 points) than the quart having lowest correction of angulation (7.40 points, P = 0.0146 for difference). The most common adverse events temporally related to surgery (i.e., within 30 d) were back pain (20 BKP, 11 NSM) new VCF (11 BKP, 7 NSM), nausea/vomiting (12 BKP, 4 NSM), and urinary tract infection (10 BKP, 3 NSM). Several other adverse events were possibly related to patient positioning in the operating room.



Compared with NSM, BKP improves patient quality of life and pain averaged during 24 months and results in better improvement of index vertebral body kyphotic angulation. Perioperative complications may be reduced with more care in patient positioning.
Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease.

Mutations in the glucocerebrosidase gene (GBA) are associated with Gaucher's disease, the most common lysosomal storage disorder. Parkinsonism is an established feature of Gaucher's disease and an increased frequency of mutations in GBA has been reported in several different ethnic series with sporadic Parkinson's disease. In this study, we evaluated the frequency of GBA mutations in British patients affected by Parkinson's disease. We utilized the DNA of 790 patients and 257 controls, matched for age and ethnicity, to screen for mutations within the GBA gene. Clinical data on all identified GBA mutation carriers was reviewed and analysed. Additionally, in all cases where brain material was available, a neuropathological evaluation was performed and compared to sporadic Parkinson's disease without GBA mutations. The frequency of GBA mutations among the British patients (33/790 = 4.18%) was significantly higher (P = 0.01; odds ratio = 3.7; 95% confidence interval = 1.12-12.14) when compared to the control group (3/257 = 1.17%). Fourteen different GBA mutations were identified, including three previously undescribed mutations, K7E, D443N and G193E. Pathological examination revealed widespread and abundant alpha-synuclein pathology in all 17 GBA mutation carriers, which were graded as Braak stage of 5-6, and had McKeith's limbic or diffuse neocortical Lewy body-type pathology. Diffuse neocortical Lewy body-type pathology tended to occur more frequently in the group with GBA mutations compared to matched Parkinson's disease controls. Clinical features comprised an early onset of the disease, the presence of hallucinations in 45% (14/31) and symptoms of cognitive decline or dementia in 48% (15/31) of patients. This study demonstrates that GBA mutations are found in British subjects at a higher frequency than any other known Parkinson's disease gene. This is the largest study to date on a non-Jewish patient sample with a detailed genotype/phenotype/pathological analyses which strengthens the hypothesis that GBA mutations represent a significant risk factor for the development of Parkinson's disease and suggest that to date, this is the most common genetic factor identified for the disease.
The recovery group project: development of an intervention led jointly by peer and professional counselors.

The objective of this study was to develop and evaluate a low-cost, strengths-based group intervention led jointly by peer counselors and professional counselors to foster recovery among adults with serious mental illnesses.  1 included development of materials and a feasibility pilot, with participants recruited from community mental health centers (CMHCs). Cohorts 2 and 3 included a small randomized controlled trial with participants recruited from members of a not-for-profit, integrated health plan. Cohorts 4 and 5 involved evaluation of the most appropriate length for the intervention with a pre-post design that allowed intervention length to vary between 12 and 18 sessions; participants and peer leaders were recruited from two CMHCs (N=82).  Participants were very satisfied with the recovery-focused group intervention, preferred a greater number of weekly sessions (17 or 18 sessions), and reported improved outcomes across multiple domains.  Using peer-developed materials and a combination of peer and professional counselors as group leaders is feasible to offer and valuable to participants. Outcomes measures suggest that the intervention has potential to facilitate recovery in multiple domains.
HIV-1 drug resistance surveillance in antiretroviral treatment-naive individuals from a reference hospital in Guatemala, 2010-2013.

The recent expansion of antiretroviral treatment (ART) coverage in middle/low-income countries has been associated with increasing prevalence of HIV pre-ART drug resistance (PDR). We assessed PDR prevalence, patterns, and trends in Guatemala. Blood samples from 1,084 ART-naive individuals, enrolled from October 2010 to December 2013 at the Roosevelt Hospital in Guatemala City, were obtained. PDR was evaluated using the WHO mutation list for transmitted drug resistance (TDR) surveillance. An overall PDR prevalence of 7.3% (95% CI 5.8-9.0%) was observed for the whole study period. TDR to nonnucleoside reverse transcriptase inhibitors (NNRTI) was the highest (4.9%, p<0.001), followed by nucleoside RT inhibitors (1.8%) and protease inhibitors (1.0%). No significant trends in PDR prevalence were observed during the study period. However, higher NNRTI PDR levels were found in individuals with >500 and 350-500 CD4(+) T cells/μl (7.4% and 8.7%, respectively) compared to individuals with <350 CD4(+) T cells/μl (3.7%; p=0.039 and p=0.007, respectively), as well as a tendency of higher levels of NNRTI transmitted drug resistance (DR) in individuals with recent infection determined by HIV incidence tests (9.7%), suggesting increasing trends in time. Clusters of viruses with NNRTI PDR suggesting complex transmission networks were observed. No associations between PDR and demographic variables were found. PDR in Guatemala remains at an intermediate level. Nevertheless, we have shown evidence suggesting increasing trends in NNRTI PDR, which need to be taken into account in national HIV management policies.