nils-herrmann/clean_scirepeval huggingface dataset:
Vaccination of colorectal cancer patients with TroVax given alongside chemotherapy (5-fluorouracil, leukovorin and irinotecan) is safe and induces potent immune responses

Modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax®) has been evaluated in an open label phase II study in metastatic colorectal cancer patients. The primary objective was to assess the safety and immunogenicity of TroVax injected before, during and after treatment with 5-fluorouracil, leukovorin and irinotecan. TroVax was administered to 19 patients with metastatic colorectal cancer. Twelve patients had blood samples taken following each of the six injections and were considered to be evaluable for assessment of immunological responses. Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector MVA were monitored throughout the study. Administration of TroVax alongside chemotherapy was safe and well tolerated with no SAEs attributed to the vaccine and no enhancement of chemo-related toxicity. Of the 12 patients who were evaluable for assessment of immune responses, ten mounted 5T4-specific antibody responses with titers ranging from 10 to >5,000. IFNγ ELISPOT responses specific for 5T4 were detected in 11 patients with frequencies exceeding one in 1,000 PBMCs in five patients. Eight patients presented with elevated circulating CEA concentrations, six of whom showed decreases in excess of 50% during chemotherapy and four had CEA levels which remained stable for >1 month following completion of chemotherapy. Of the 19 intention to treat (ITT) patients, one had a CR, six had PRs and five had SD. Potent 5T4-specific cellular and/or humoral immune responses were induced in all 12 evaluable patients and were detectable in most patients during the period in which chemotherapy was administered. These data demonstrate that TroVax can be layered on top of chemotherapy regimens without any evidence of enhanced toxicity or reduced immunological or therapeutic efficacy.
Comparative study of combined bevacizumab/targeted photocoagulation vs bevacizumab alone for macular oedema in ischaemic branch retinal vein occlusions.

To investigate whether targeted retinal photocoagulation (TRP) of peripheral non-perfused areas (NPAs) could prevent the recurrence of macular oedema (ME) due to branch retinal vein occlusion (BRVO) after intravitreal bevacizumab injection (IVB).



Eyes received 1.25 mg IVB only (IVB group) or combined with TRP (IVB + TRP group) of NPAs, more than 5 disc areas identified by fluorescein angiography in the patients with ME secondary to BRVO. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) determined by optical coherence tomography were measured every month for 6 months.



Thirty-eight patients were enrolled and randomized to IVB group (n = 19) and IVB + TRP group (n = 19). Both groups showed similar thinning in CRT at 1 week after IVB, IVB + TRP group maintained thinner retina at 2 (p = 0.0072) and 3 (p = 0.0086) months compared with IVB group in whom turned to thickened almost back to baseline at 3 months. The number of reinjections in IVB group (1.58 ± 0.69) was significantly greater (p = 0.0025) than that in IVB + TRP group (0.83 ± 0.62). BCVA significantly improved at 6 month in IVB + TRP group (p = 0.015), but not in IVB group.



TRP of NPAs reduced the amount of ME recurrence following IVB compared to IVB alone.
Polyposis syndromes in children and adolescents: a case series data analysis.

Polyposis syndromes in children are distinct entities clinically and pathologically. These syndromes have multiple genetic characteristics, with development of polyps at various sites of the gastrointestinal (GI) tract, and are associated with an increased risk of colon cancer. They are relatively rare, and have mostly been characterized in the adult population, whereas little epidemiologic data have been reported in children.



The aim of this study was to summarize the pediatric experience collected over a period of 11 years on polyposis syndromes in three major Israeli tertiary centers.



Medical records of children below 18 years old and their families, diagnosed with polyposis syndromes between 1999 and 2010, were reviewed. The data included disease presentation, genetic profile, surveillance, and treatment.



Fifty patients with polyposis syndromes were identified. The most frequent syndrome was familial adenomatous polyposis (FAP) in 33 children (66%), of whom 25 children (75.7%) had a known mutation. The mean age at presentation was 10.6±3.9 years (range 4-17 years). Most children were examined because of a family history of a polyposis syndrome (42 children, 84%). Among symptomatic children (32 children), the most frequent complaint was rectal bleeding (42%), followed by abdominal pain (22%), intussusception (10%), and diarrhea (4%). The youngest symptomatic patient was 4 years old at presentation, with rectal bleeding.All patients underwent multiple colonoscopies and upper GI endoscopies according to specific guidelines. Thirteen children underwent colonic surgery (39%); nine children had FAP. Adenocarcinoma of the colon was diagnosed in a 12.5-year-old child.



In this cohort study, FAP was the most common type of polyposis syndrome diagnosed in this pediatric population. Colon cancer was present at the onset of symptoms in a 12.5-year-old patient with FAP. We therefore recommend strict adherence to the hereditary GI cancer guidelines to prevent morbidity and mortality in FAP and other inherited polyposis syndromes.
Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction: a randomized trial.

Rapid opioid detoxification with opioid antagonist induction using general anesthesia has emerged as an expensive, potentially dangerous, unproven approach to treat opioid dependence.



To determine how anesthesia-assisted detoxification with rapid antagonist induction for heroin dependence compared with 2 alternative detoxification and antagonist induction methods.



A total of 106 treatment-seeking heroin-dependent patients, aged 21 through 50 years, were randomly assigned to 1 of 3 inpatient withdrawal treatments over 72 hours followed by 12 weeks of outpatient naltrexone maintenance with relapse prevention psychotherapy. This randomized trial was conducted between 2000 and 2003 at Columbia University Medical Center's Clinical Research Center. Outpatient treatment occurred at the Columbia University research service for substance use disorders. Patients were included if they had an American Society of Anesthesiologists physical status of I or II, were without major comorbid psychiatric illness, and were not dependent on other drugs or alcohol.



Anesthesia-assisted rapid opioid detoxification with naltrexone induction, buprenorphine-assisted rapid opioid detoxification with naltrexone induction, and clonidine-assisted opioid detoxification with delayed naltrexone induction.



Withdrawal severity scores on objective and subjective scales; proportions of patients receiving naltrexone, completing inpatient detoxification, and retained in treatment; proportion of opioid-positive urine specimens.



Mean withdrawal severities were comparable across the 3 treatments. Compared with clonidine-assisted detoxification, the anesthesia- and buprenorphine-assisted detoxification interventions had significantly greater rates of naltrexone induction (94% anesthesia, 97% buprenorphine, and 21% clonidine), but the groups did not differ in rates of completion of inpatient detoxification. Treatment retention over 12 weeks was not significantly different among groups with 7 of 35 (20%) retained in the anesthesia-assisted group, 9 of 37 (24%) in the buprenorphine-assisted group, and 3 of 34 (9%) in the clonidine-assisted group. Induction with 50 mg of naltrexone significantly reduced the risk of dropping out (odds ratio, 0.28; 95% confidence interval, 0.15-0.51). There were no significant group differences in proportions of opioid-positive urine specimens. The anesthesia procedure was associated with 3 potentially life-threatening adverse events.



These data do not support the use of general anesthesia for heroin detoxification and rapid opioid antagonist induction.
Tapering dose of inhaled budesonide in subjects with mild-to-moderate persistent asthma treated with montelukast: a 16-week single-blind randomized study.

Pharmacological therapy with inhaled steroids (IS) is currently considered the gold-standard of treatment for mild-persistent asthma. Leukotriene receptor antagonist drugs (LTRAs) play an important role associated with IS, allowing dose tapering and maintaining control of asthma symptoms. The aim of this study was to determine the effectiveness of montelukast (MON) to allow tapering of the inhaled dose of budesonide (BUD) in patients with mild-moderate persistent asthma. This 16-wk single-blind randomized study included 40 asthmatic patients divided in 2 treatment groups. After a run-in period (4 wk), in which all patients inhaled 400 microg of BUD twice daily (bid), group A (20 patients) received MON (oral, 10 mg/day) combined with inhaled BUD (400 microg/bid), while group B (20 patients) was treated with BUD for the whole period of the study. In both groups, at every 4 wk the dose of BUD was halved. After 12 wk of treatment the mean value of forced expiratory volume during the first sec (FEV1, as % of predicted value) was significantly greater in group A compared with group B (94 +/- 7.5 vs 83.1 +/- 6.9; p<0.005). The mean values of peak expiratory flow (PEF), the percentages of asthmatic exacerbations, and the use of beta2-short-acting agonist (SABA) were similar in the 2 groups at 4, 8, and 12 wk. In conclusion, in patients with mild-moderate persistent asthma, MON therapy is useful in tapering the dose of IS in order to reduce its side effects and to maintain the clinical stability of the disease.
Effects of continuous positive airway pressure on systemic inflammation in patients with moderate to severe obstructive sleep apnoea: a randomised controlled trial.

Obstructive sleep apnoea syndrome (OSAS) has been associated with cardiovascular disease in epidemiological and observational studies. Continuous positive airway pressure (CPAP) is the treatment of choice for OSAS, but the impact of this intervention on systemic inflammation involved in the atherosclerotic process remains unclear.



100 men with moderate-severe OSAS were randomised to therapeutic (n = 51) or subtherapeutic (n = 49) CPAP treatment for 4 weeks to investigate the effects of active treatment on inflammatory markers such as highly sensitive C reactive protein (hsCRP), interleukin (IL)6, interferon gamma (IFNgamma) and anti-inflammatory adiponectin.



4 weeks of therapeutic CPAP did not significantly change blood levels of hsCRP compared with the subtherapeutic control group (difference between median changes -0.24 mg/l (95% CI -0.88 to +0.24); p = 0.30). Plasma levels of IL6 and IFNgamma did not change significantly following therapeutic compared with subtherapeutic CPAP (difference between median changes +0.52 and -0.07 pg/ml (95% CI -0.72 to +1.94 and -0.81 to +0.44); p = 0.45 and p = 0.82, respectively). Furthermore, 4 weeks of therapeutic CPAP did not significantly change levels of adiponectin in plasma compared with the subtherapeutic control group (difference between median changes +0.05 pg/ml (95% CI -0.36 to +0.47); p = 0.84). If patients with hsCRP values above 8 mg/l at baseline were excluded, differences between the changes in hsCRP, IL6, IFNgamma and adiponectin after 4 weeks of CPAP were smaller, and again not statistically different between groups.



4 weeks of CPAP treatment has no beneficial effect on blood markers of inflammation and adiponectin in patients with moderate-severe obstructive sleep apnoea.
Increased active PTH(1–84) fraction as a predictor of poor mortality in male hemodialysis patients

We reported previously that serum parathyroid hormone [PTH(1–84)]/intact PTH[PTH(1–84) + PTH(7–84)] ratio provides the better marker for parathyroid function and bone turnover state than serum PTH level itself. The present study demonstrated that higher PTH(1–84)/intact PTH ratio, but not serum PTH(1–84) and intact PTH, predicted higher all-cause mortality in 177 male hemodialysis patients. We reported that PTH(1–84)/intact PTH ratio provides a clinically relevant marker for parathyroid function and the resultant bone turnover state. The purpose of our study was to investigate the association of PTH(1–84)/intact PTH ratio with all-cause mortality (ACM) in male hemodialysis patients. The study was performed for 70 months. Serum PTH in 177 male hemodialysis patients was measured with PTH(1–84)-specific whole PTH assay and intact PTH assay which cross-reacts with N-truncated PTH including PTH(7–84). The patients (n = 177) were divided into higher and lower halves based on serum levels of PTH(1–84)/intact PTH ratio (cutoff value, 0.484), intact PTH (143.8 pg/mL), and PTH(1–84) (64.1 pg/mL). In Kaplan–Meier analysis, the higher group in whole PTH/intact PTH ratio had significantly higher ACM than the lower group (P = 0.020 by log-rank test), in contrast with the insignificant difference between the higher and lower groups in intact PTH and PTH(1–84). Multivariate Cox regression hazard analysis identified higher log [PTH(1–84)/intact PTH ratio], but not log intact PTH or log PTH(1–84) as a significant independent predictor [hazard ratio 14.428 (95 % CI 2.486–83.728)] for ACM after adjustment for various factors including age, hemodialysis duration, presence/absence of diabetes mellitus, BMI, log C-reactive protein, serum albumin, calcium, and phosphate. The association existed between log [PTH(1–84)/intact PTH ratio] and ACM in those without vitamin D administration (n = 95). Higher PTH(1–84)/intact PTH ratio, which provides a relevant marker for parathyroid function, may be a significant predictor of ACM in male hemodialysis patients.
Cyclooxygenase inhibition improves endothelium-dependent vasodilatation in patients with chronic renal failure.

Some studies have demonstrated beneficial effects of L-arginine as a substrate for nitric oxide synthesis, and diclofenac as an inhibitor of cyclooxygenase (COX)-derived vasoconstrictive agents on vascular responses in humans during several pathological conditions. The aim of the present study was to investigate the acute effects of L-arginine and diclofenac on endothelium-dependent vasodilatation (EDV) and endothelium-independent vasodilatation (EIDV) in patients with chronic renal failure (CRF).



Effects of L-arginine and diclofenac on EDV and EIDV were measured in 15 patients with CRF and in 15 healthy controls by means of forearm blood flow measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (2 and 4 micro g/min evaluating EDV) and sodium nitroprusside (5 and 10 micro g/min evaluating EIDV).



L-Arginine infusion increased methacholine-induced vasodilatation both in patients with CRF and healthy controls. Diclofenac infusion increased methacholine-induced vasodilatation only in patients with CRF. There was no significant change in nitroprusside-induced vasodilatation after L-arginine and diclofenac infusions both in patients with CRF and healthy controls.



These results suggest that COX inhibition reduces the levels of a prostanoid-derived vasoconstrictive agent contributing to the impaired EDV in patients with CRF, while in this age group L-arginine improves EDV regardless of renal function.
Acute respiratory infection in patients with cystic fibrosis with mild pulmonary impairment: comparison of two physiotherapy regimens.

Chest physiotherapy is an essential part of the management of cystic fibrosis, yet comparatively few studies have investigated the commonly used forms of chest physiotherapy during acute respiratory exacerbations. Fifteen subjects with cystic fibrosis and predominantly mild pulmonary impairment completed a randomised cross-over trial with 24 hours between treatments. The active cycle of breathing techniques (ACBT) assisted by a physiotherapist was compared with the ACBT performed independently by the patient. Measurement outcomes included pulmonary function tests, indirect calorimetry and oximetry parameters. Energy expenditure was not significantly different between the two treatment regimens, though significant improvements in pulmonary function were apparent 24 hours following the therapist-assisted ACBT. In this group of subjects, neither form of treatment proved superior in terms of energy consumption, but a reduction in airways obstruction was observed as a carry-over effect following the therapist-assisted ACBT.
Multicenter double-blind comparison of sertraline and desipramine for concurrent obsessive-compulsive and major depressive disorders.

Serotonin reuptake inhibitors (SRIs) have demonstrated consistent efficacy in the treatment of obsessive-compulsive disorder (OCD), while agents that are primarily norepinephrine reuptake inhibitors have not. Comparable efficacy has been demonstrated for SRI and non-SRI antidepressants in uncomplicated major depressive disorder (MDD). This multicenter trial is the first comparison of an SRI (sertraline) and a non-SRI antidepressant (desipramine) in the treatment of OCD with concurrent MDD.



One hundred sixty-six patients diagnosed using structured clinical interviews and recruited from 16 treatment sites were randomly assigned to double-blind treatment with either sertraline (up to 200 mg/d) or desipramine (up to 300 mg/d) over 12 weeks. Measures of severity of OCD and MDD symptoms, as well as adverse effects of the medications, were monitored over the course of the treatment period.



Patients assigned to sertraline responded significantly better at end point on measures of OCD and MDD symptoms compared with patients assigned to desipramine. Sertraline was also associated with a significantly greater number of patients who achieved a "robust" improvement in OCD symptoms (> or =40% reduction) compared with desipramine. More patients receiving desipramine than sertraline discontinued treatment because of adverse events.



The SRI sertraline was more effective in reducing MDD and OCD symptoms than the primarily norepinephrine reuptake inhibitor desipramine for patients with concurrent OCD and MDD.
Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B.

To determine the efficacy of tenofovir disoproxil fumarate (TDF) in adults with chronic hepatitis B virus (HBV) infection who had previously failed lamivudine (LAM) and had significant viral replication (HBV DNA >10⁵ copies/ml if HBeAg positive, > 10⁴ copies/ml if HBeAg negative) despite at least 24 weeks of treatment with adefovir dipivoxil (ADV).



A prospective open-label study of TDF 300 mg daily. Patients receiving combination ADV/LAM prior to baseline were switched to TDF/LAM.



Multiple tertiary referral centres.



Sixty patients were enrolled. The median age was 48.5 years (range 21e80), 46 (77%) were male and 40 (67%) were HBeAg positive. Thirty-eight patients (63%) were switched from ADV to TDF, the remainder from ADV/LAM to TDF/LAM. At baseline, substitutions conferring resistance to LAM or ADV were present in 20 patients (33%) and 17 patients (28%), respectively. The median baseline viral load was 5.33 log₁₀ IU/ml (range 2.81-8.04). Patients initially treated with TDF monotherapy with persistent viral replication at or after 24 weeks were switched to TDF/LAM. The main outcome measures were change in HBV viral load from baseline and percentage of patients achieving an undetectable viral load (<15 IU/ml).



Results are reported at 96 weeks of treatment. One patient discontinued TDF at 10 days due to rash. The time-weighted change in viral load from baseline to week 12 was -2.19 log10 IU/ml overall. The median change in HBV DNA from baseline to weeks 12, 24, 48 and 96 was -2.86, -3.23, -3.75 and -4.03 log₁₀ IU/ml, respectively. At 48 and 96 weeks, 27/59 (46%) and 38/59 (64%) patients achieved a HBV DNA <15 IU/ml. The response was independent of baseline LAM therapy or mutations conferring ADV resistance.



In heavily pretreated patients with a high rate of genotypic resistance, TDF retains significant activity against HBV although this appears diminished in comparison with studies of naïve patients.
Late Remote Ischemic Preconditioning Provides Benefit to Patients Undergoing Elective Percutaneous Coronary Intervention

To assess whether late remote ischemic preconditioning (L-RIPC) is effective in myocardial protection in patients with ischemic heart disease undergoing elective percutaneous coronary intervention (PCI). L-RIPC is exerted by newly synthesized cardioprotective proteins. The cardioprotective effects of L-RIPC are more durable. 200 consecutive patients undergoing elective PCI were randomized to receive L-RIPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mmHg around the upper arm, followed by 5-min intervals of reperfusion) or control (an uninflated cuff around the arm) at 18 h before PCI. Creatine phosphokinase (CK), its cardiac isoenzyme (CK-MB), troponin I (TNI), and high-sensitivity C-reactive protein (hs-CRP) levels were measured at 24 h after PCI. Adverse events’ rates at 6 months were assessed. Compared with the control group, patients in L-RIPC group were observed with significantly lower incidences in Chest pain score >1 and ECG ST deviation >1 mm (P < 0.05). The median TNI, CK, and CK-MB concentrations at 24 h were lower in the L-RIPC group (0.009 vs. 0.036 ng/mL, 123 vs. 186 IU/L, 15 vs. 27 IU/L; P < 0.05). There was no statistical difference in hs-CRP between two groups. At 6 months, the adverse events’ rate was lower in the L-RIPC group (P = 0.036). L-RIPC is effective in myocardial protection in patients undergoing elective PCI and reduces adverse events’ rate at 6 months.
Survival improvement of poor-prognosis AML/MDS patients by maintenance treatment with low-dose chemotherapy and differentiating agents

We evaluated a maintenance, post-remission treatment with low-dose chemotherapy plus differentiating agents on poor-prognosis acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients ineligible to allografting. Patients had either age over 60 and/or secondary AML, therapy-related AML, previous relapse, high-risk MDS. Forty-five patients received the maintenance therapy based on two alternated schedules: (a) 6-thioguanine + 13-cis retinoic acid + dihydroxylated vitamin D3 and (b) low-dose cytarabine + 6-mercaptopurine + all-trans retinoic acid + dihydroxylated vitamin D3. We compared their outcome, at a median follow-up of 52 months, to that of a matched population of 49 patients who stopped treatments after consolidation. Maintenance group had a lower relapse incidence (70.3 vs. 86.4 % at 5 years p = 0.007) and a longer disease-free survival (median 21.2 vs. 8.7 months, p = 0.017). The relapse reduction improved overall survival: median 40.4 months (35.9 % at 5 years) for maintenance group vs. 15.8 (14.2 % at 5 years) for controls (p = 0.005). At multivariate Cox analysis, both cytogenetic and maintenance therapies resulted independent outcome predictors for overall survival. Maintenance treatment also reduced minimal residual disease (detected by WT1 and CBFβ-MYH11) in five of eight evaluable patients. The present results suggest that our strategy of maintenance therapy might improve the outcome of poor-risk AML/MDS patients.