nils-herrmann/clean_scirepeval huggingface dataset:
Do fluctuations in endogenous melatonin levels predict the occurrence of postoperative cognitive dysfunction (POCD)?

Delirium is a complex neuropsychiatric disorder that has an adverse impact on CNS function. Abnormal fluctuation of melatonin secretion occurs in the postoperative delirium (POD) in elderly patients. POD is strongly associated with early postoperative cognitive dysfunction (POCD). The aim of this study is to test if significant fluctuation of melatonin secretion perioperatively might indicates POCD. A total of 97 patients, ages 65-80 years, scheduled for major orthopedic surgery or abdominal surgery which was expected to last more than 2 h, were consecutively recruited into this study. Neuropsychological evaluation was performed 1 d before and one week after surgery. Morning urine samples were collected on the day of surgery and on days 1, 2 and 7 after surgery. The 6-SMT/creatinine ratio (M/C ratio) was employed to give an objective estimate of urine 6-SMT concentration. Ultimately, 95 patients completed assessments and were included in the analysis. POCD was found in 30 patients (31.6%) at 1 week after operation. There was significant fluctuation in urinary 6-SMT in 39 of the 95 patients (as evidenced by urinary 6-SMT levels increased or decreased by more than twofold compared with their preoperative baseline). Fluctuations in 6-SMT levels occurred on different days and in some patients lasted for more than 1 d. The incidence of POCD in patients with 6-SMT fluctuation was significantly higher (p < 0.01). The results indicate that in the first week after major noncardiac surgery, POCD occurs in a significant proportion of people, and is linked to fluctuations in endogenous melatonin levels. Measurement of urinary 6-SMT during the perioperative period may assist the diagnosis of POCD.
Migraine prophylaxis by anodal transcranial direct current stimulation, a randomized, placebo-controlled trial.

Migraine is a common headache syndrome in adult populations. Prophylaxis is necessary to improve the quality of life but some patients with migraine have contraindication or suffer from side effects of medication, and therefore, establishing non-medical, neuromodulatory approaches is necessary. Past evidence had shown that consecutive motor cortex (M1) stimulation with anodal transcranial direct current stimulation (tDCS) was effective to relieve central pain.



To determine whether 20 consecutive days of the left M1 can be an effective prophylactic treatment for migraine.



Forty-two episodic migraine patients who had never received any prophylactic treatment, failed prophylactic treatment, or discontinued treatment due to adverse events were recruited in the present study. Patients were randomized to receive either active tDCS or sham tDCS 1mA, 20 m for 20 consecutive days and followed up for 12 weeks. Differences between and within groups were determined using repeated measures ANOVA. The level of significance was set at p < 0.05.



Thirty-seven patients participated in the final analyses (active: n = 20, sham: n = 17). Between-groups comparison of attack frequency, pain intensity, and abortive medications used were performed at 4, 8, and 12 weeks after treatment. The results showed statistically significant reduction in attack frequency and abortive medications at week 4 and 8 after treatment. The pain intensity was statistically significant reduced at week 4, 8, and 12. All patients tolerated the tDCS well without any serious adverse events.



The present study suggests that anodal M1 tDCS may be a safe and useful clinical tool in migraine prophylaxis. The mechanism of action of anodal tDCS on neuromodulation in migraine patients needs further investigation.
Impeded alveolar-capillary gas transfer with saline infusion in heart failure.

The microvascular pulmonary endothelium barrier is critical in preventing interstitial fluid overflow and deterioration in gas diffusion. The role of endothelium in transporting small solutes in pathological conditions, such as congestive heart failure (CHF), has not been studied. Monitoring of pulmonary gas transfer during saline infusion in CHF was used to probe this issue. Carbon monoxide diffusion (DL(CO)), its membrane diffusion (D(M)) and capillary blood volume (V(C)) subcomponents, and mean right atrial (rap) and mean pulmonary wedge (wpp) pressures after saline or 5% D-glucose solution infusions were compared with baseline in 26 moderate CHF patients. Saline was also tested in 13 healthy controls. In patients, 750 mL of saline lowered DL(CO) (-8%, P<0.01 versus baseline), D(M) (-10%, P<0.01 versus baseline), aldosterone (-29%, P<0.01 versus baseline), renin (-52%, P<0.01 versus baseline), and hematocrit (-6%, P<0.05 versus baseline) and increased V(C) (20%, P<0.01 versus baseline), without changing rap and wpp. Saline at 150 mL produced qualitatively similar results regarding DL(CO) (-5%, P<0.01 versus baseline), D(M) (-7%, P<0.01 versus baseline), V(C) (9%, P<0.01 versus baseline), rap, wpp, aldosterone (-9%, P<0.05 versus baseline), and renin (-14%, P<0.05 versus baseline). Glucose solution (750 mL), on the contrary, increased DL(CO) (5%, P<0.01 versus 750 mL of saline) and D(M) (11%, P<0.01 versus 750 mL of saline) and decreased V(C) (-9, P<0.01 versus 750 mL of saline); aldosterone (-40%), renin (-41%), hematocrit (-3%), rap, and wpp behaved as they did after saline infusion. In controls, responses to both saline amounts were similar to responses in CHF patients regarding aldosterone, renin, hematocrit, rap, and wpp, whereas DL(CO), D(M), and V(C) values tended to rise. Hindrance to gas transfer (reduced DL(CO) and D(M)) with salt infusion in CHF, despite an increase in V(C) and no variations in pulmonary hydrostatic forces, indicates an upregulation in sodium transport from blood to interstitium with interstitial edema. Redistribution of blood from the lungs, facilitating interstitial fluid reabsorption, or sodium uptake from the alveolar lumen by the sodium-glucose cotransport system might underlie the improved alveolar-capillary conductance with glucose.
Twenty-four hour blood pressure profiles in hypertensive patients following various formulations and dosage regimens of felodipine

The blood pressure lowering capacity of felodipine administered either as extended release tablets once or twice daily or as plain tablets twice daily has been compared in a double-blind, three-way cross-over study in 16 hypertensive patients. All the patients were on long-term treatment with 10 or 20 mg felodipine daily and other antihypertensive therapy (mainly beta-blockers) was allowed if it was kept unchanged. Non-invasive blood pressure and heart rate recordings were obtained throughout 24 hour periods using an Accutracker ambulatory system. The 24 h mean systolic and diastolic blood pressures after extended release tablets o.m. did not differ significantly from those after extended release tablets b.d. or plain tablets b.d. There was a tendency for the extended release tablets given o.m. to reduce blood pressure somewhat more in the morning, and for the extended release tablets b.d. to reduce blood pressure more during the night than the other treatments. Mean 24 h heart rate after all treatments was comparable. Manual recordings confirmed these results. Blood pressure was well-controlled throughout the 24 h period by all three treatments. The extended release tablets tended to give less extreme plasma concentrations of felodipine. This may be of value for patients with adverse vasodilator effects. For a majority of hypertensive patients the adequacy of blood pressure control and the simplicity of once daily dosing will favour the extended release tablet given once daily.
Predictors for length of hospital stay in patients with community-acquired Pneumonia: Results from a Swiss Multicenter study

Length of hospital stay (LOS) in patients with community-acquired pneumonia (CAP) is variable and directly related to medical costs. Accurate estimation of LOS on admission and during follow-up may result in earlier and more efficient discharge strategies.



This is a prospective multicenter study including patients in emergency departments of 6 tertiary care hospitals in Switzerland between October 2006 and March 2008. Medical history, clinical data at presentation and health care insurance class were collected. We calculated univariate and multivariate cox regression models to assess the association of different characteristics with LOS. In a split sample analysis, we created two LOS prediction rules, first including only admission data, and second including also additional inpatient information.



The mean LOS in the 875 included CAP patients was 9.8 days (95%CI 9.3-10.4). Older age, respiratory rate >20 pm, nursing home residence, chronic pulmonary disease, diabetes, multilobar CAP and the pneumonia severity index class were independently associated with longer LOS in the admission prediction model. When also considering follow-up information, low albumin levels, ICU transfer and development of CAP-associated complications were additional independent risk factors for prolonged LOS. Both weighted clinical prediction rules based on these factors showed a high separation of patients in Kaplan Meier Curves (p logrank <0.001 and <0.001) and a good calibration when comparing predicted and observed results.



Within this study we identified different baseline and follow-up characteristics to be strong and independent predictors for LOS. If validated in future studies, these factors may help to optimize discharge strategies and thus shorten LOS in CAP patients.
Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women.

To investigate the therapeutic effect of combined use of vitamin K(2) and D(3) on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis.



We enrolled 172 women with vertebral bone mineral density <0.98 g/cm(2) (osteopenia and osteoporosis) as measured by dual-energy X-ray absorptiometry. In this study, we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996. Subjects were randomized into four groups (each having 43 subjects in vitamin K(2) therapy group, vitamin D(3) therapy group, vitamin K(2) and D(3) combined therapy group, or a control group receiving dietary therapy alone) and treated with respective agents for 2 years, with bone mineral density was measured prior to therapy and after 6, 12, 18, and 24 months of treatment. The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide (P1CP), serum intact osteocalcin, and urinary pyridinoline. Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time (APTT) and analysis of concentrations of antithrombin III (AT III), fibrinogen, and plasminogen.



Combined therapy with vitamin K(2) and D(3) for 24 months markedly increased bone mineral density (4.92 +/- 7.89%), while vitamin K(2) alone increased it only 0.135 +/- 5.44%. The bone markers measured, revealed stimulation of both bone formation and resorption activity. We observed an increase in coagulation and fibrinolytic activity that was within the normal range, suggesting that balance was maintained in the fibrinolysis-coagulation system.



Continuous combination therapy with vitamin K(2) and D(3) may be useful for increasing vertebral bone mass in postmenopausal women. Furthermore, the increase in coagulation function observed during this therapy was within the physiological range, and no adverse reactions were observed.
Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Taxanes and anthracyclines improve the outcome of early breast cancer, although the benefit is limited to a small proportion of patients and are toxic. We prospectively looked for predictors of response to these drugs.  Four cycles of doxorubicin (75 mg/m2) or docetaxel (100 mg/m2) were compared as presurgical chemotherapy for breast cancer. Biomarkers were determined by immunohistochemistry and fluorescent in situ hybridization using prechemotherapy core biopsies. Tumors were also classified into one of the molecular intrinsic subtypes using an immunohistochemical panel of five biomarkers and genomic profiles. Single genes and intrinsic subtypes were correlated with response to doxorubicin versus docetaxel. Among the 204 evaluable patients, significant predictors of sensitivity in multivariate analysis were low topo2a expression and ER-negative status for doxorubicin and small tumor size and ER-negative status for docetaxel. Predictors of resistance in multivariate analysis were triple-negative status (ER/PgR/HER2 negative by IHC/FISH) for doxorubicin, and high TNM stage for docetaxel. Triple-negative tumors were associated with topo2a overexpression more than the other subtypes. In 94 patients with gene expression profiles, docetaxel was superior to doxorubicin in the basal-like subtype (good pathological response rate − PCR + class I of 56 vs. 0%; P = 0.034); no significant differences were observed in the other subtypes when comparing these two drugs. Low topo2a expression and ER-negative status were predictors of response to doxorubicin, while small tumor size and ER-negative status predicted response to docetaxel. Docetaxel was superior to doxorubicin in triple-negative/basal-like tumors, while no significant differences were seen in the remaining intrinsic subtypes.
O6-methylguanine-DNA methyltransferase depletion and DNA damage in patients with melanoma treated with temozolomide alone or with lomeguatrib

We evaluated the pharmacodynamic effects of the O6-methylguanine-DNA methyltransferase (MGMT) inactivator lomeguatrib (LM) on patients with melanoma in two clinical trials. Patients received temozolomide (TMZ) for 5 days either alone or with LM for 5, 10 or 14 days. Peripheral blood mononuclear cells (PBMCs) were isolated before treatment and during cycle 1. Where available, tumour biopsies were obtained after the last drug dose in cycle 1. Samples were assayed for MGMT activity, total MGMT protein, and O6-methylguanine (O6-meG) and N7-methylguanine levels in DNA. MGMT was completely inactivated in PBMC from patients receiving LM, but detectable in those on TMZ alone. Tumours biopsied on the last day of treatment showed complete inactivation of MGMT but there was recovery of activity in tumours sampled later. Significantly more O6-meG was present in the PBMC DNA of LM/TMZ patients than those on TMZ alone. LM/TMZ leads to greater MGMT inactivation, and higher levels of O6-meG than TMZ alone. Early recovery of MGMT activity in tumours suggested that more protracted dosing with LM is required. Extended dosing of LM completely inactivated PBMC MGMT, and resulted in persistent levels of O6-meG in PBMC DNA during treatment.
Controlled trial of disodium cromoglycate in chronic persistent ulcerative colitis.

Oral disodium cromoglycate (200 mg qds) has been tested in 26 patients with ulcerative colitis that was resistant to medical treatment. In a double-blind crossover trial disodium cromoglycate and placebo were added to conventional treatment in random order, each for four weeks. There was no significant difference in therapeutic effect between disodium cromoglycate and placebo.
Effects of Dietary n-3 Fatty Acids on Hepatic and Peripheral Insulin Sensitivity in Insulin-Resistant Humans

Dietary n-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevent insulin resistance and stimulate mitochondrial biogenesis in rodents, but the findings of translational studies in humans are thus far ambiguous. The aim of this study was to evaluate the influence of EPA and DHA on insulin sensitivity, insulin secretion, and muscle mitochondrial function in insulin-resistant, nondiabetic humans using a robust study design and gold-standard measurements.



Thirty-one insulin-resistant adults received 3.9 g/day EPA+DHA or placebo for 6 months in a randomized double-blind study. Hyperinsulinemic-euglycemic clamp with somatostatin was used to assess hepatic and peripheral insulin sensitivity. Postprandial glucose disposal and insulin secretion were measured after a meal. Measurements were performed at baseline and after 6 months of treatment. Abdominal fat distribution was evaluated by MRI. Muscle oxidative capacity was measured in isolated mitochondria using high-resolution respirometry and noninvasively by magnetic resonance spectroscopy.



Compared with placebo, EPA+DHA did not alter peripheral insulin sensitivity, postprandial glucose disposal, or insulin secretion. Hepatic insulin sensitivity, determined from the suppression of endogenous glucose production by insulin, exhibited a small but significant improvement with EPA+DHA compared with placebo. Muscle mitochondrial function was unchanged by EPA+DHA or placebo.



This study demonstrates that dietary EPA+DHA does not improve peripheral glucose disposal, insulin secretion, or skeletal muscle mitochondrial function in insulin-resistant nondiabetic humans. There was a modest improvement in hepatic insulin sensitivity with EPA+DHA, but this was not associated with any improvements in clinically meaningful outcomes.
Large breast size as a risk factor for late adverse effects of breast radiotherapy: is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation?

Large breast size is associated with an increased risk of late adverse effects after breast conservation surgery and radiotherapy, even when 3D dosimetry is used. The purpose of this study is to test the hypothesis that residual dose inhomogeneity is sufficient to explain the association.



Patients previously treated after breast conservation surgery with whole breast radiotherapy using 3D dosimetry and followed up in the UK FAST hypofractionation trial were selected for this analysis. The residual level of dose inhomogeneity across the whole breast treatment volume was used to test for association between residual dosimetry and post-treatment change in breast appearance at 2 years post-radiotherapy.



At 2 years, 201/279 (72%) of women had no change in photographic breast appearance, 61 (22%) had mild change and 17 (6%) had marked change. Breast size and dosimetry were both significantly associated with late effects in univariate analyses, but only breast size remained an independent significant risk factor for change in breast appearance when included in a multiple regression model together with other prognostic factors (p=0.006 for trend).



Large-breasted women are more likely to suffer change in breast size and shape after whole breast radiotherapy delivered using 3D dosimetry, but residual dose inhomogeneity is insufficient to explain the association.
Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia.

The outcome for adult patients with BCR-ABL-positive acute lymphoblastic leukemia (ALL) remains dismal and long-term survival can hardly be achieved except by allogeneic hematopoietic stem cell transplantation (HSCT). The Japan Adult Leukemia Study Group (JALSG) has recently started a phase 2 trial with intensive chemotherapy and imatinib for newly diagnosed BCR-AB-positive ALL patients, and we present here the interim results for the first 24 patients. All patients except one case of early death (96%) attained complete remission (CR) after a single course of remission induction therapy. Polymerase chain reaction (PCR) negativity was achieved in 28% of the patients on day 28, in 50% on day 63, and in up to 78% during the follow-up period. The toxicity profile was almost similar to that with chemotherapy alone. As a result, 15 patients (63%) could receive an allogeneic HSC transplant during their first CR. Although the number of patients is small and the observation period is too short, the combination therapy is very promising and produces high-quality CR for most newly diagnosed patients with BCR-ABL-positive ALL. This is especially useful because it provides the patients with a better chance to receive an allogeneic HSC transplant.
Whole-body versus segmental bioelectrical impedance analysis in patients with edema of the upper limb after breast cancer treatment.

The purpose of this study was to compare whole-body (50 kHz alternating current) and segmental (5 kHz alternating current) bioelectrical impedance analysis (BIA) in the assessment of manifested edema of the upper limbs.



Whole-body and segmental BIA were performed in 30 patients with edema of the upper limb following breast cancer treatment.



Pearson correlation coefficient comparing both measurements was 0.8891 (p-value <0.0001) with corresponding least squares (r(2)) of 0.7904.



Whole-body BIA seems to be a suitable method in the assessment of manifested edema of the upper limbs.
Changes in Osteoblastic Activity in Patient Who Received Bortezomib as Second Line Treatment for Plasma Cell Myeloma: A Prospective Multicenter Study

We conducted a prospective multicenter study identifying the role of bortezomib in patients with relapsed or refractory plasma cell myeloma (PCM) in bone resorption and formation via bone turnover markers. A total of 104 patients received at least 1 cycle of bortezomib. Most of them had advanced disease (n = 89). Among them, 75 patients completed 4 cycles of treatment. Most of the patients (81.7%) were treated in combination with steroid. After the 4th cycle treatment, 47 of 75 patients achieved CR, nCR, VGPR, and PR (64.4%), while 26 patients achieved less than PR (35.6%). The proportion of patients who achieved ≥ PR increased as patients received more treatment cycles, reaching 90% after the 8th cycle. DKK-1 levels decreased significantly posttreatment. Bone formation markers (bALP and OC) and osteoclast regulator such as sRANKL also decreased significantly. These findings were observed primarily in patients who received steroid and who had a longer disease duration. While sRANKL demonstrated significant reduction posttreatment, osteoprotegerin (OPG) level did not significantly change posttreatment, resulting in a decreased sRANKL/OPG ratio (P = 0.037). In conclusion, our clinical data suggest that treatment with bortezomib and steroid may rearrange the metabolic balance between osteoblast and osteoclast activities in PCM.
Safety and effectiveness of oral quinidine in cardioversion of persistent atrial fibrillation.

The effectiveness of oral quinidine for conversion of atrial fibrillation to sinus rhythm was evaluated in 49 patients with persistent atrial fibrillation on anticoagulation therapy. Atrial fibrillation was considered as persistent when the duration was longer than 3 days but less than 6 months.



Patients received orally one to 7 doses of 150 mg hydroquinidine hydrochloride every one hour until restoration of sinus rhythm, or to a maximum of 7 tablets. Patients who were not converted underwent elective electrical cardioversion.



Thirty-nine of 49 patients (79.6%) were converted with quinidine and only one of the remaining 10 was converted with electrical cardioversion. Quinidine had no significant effect on blood pressure or unexpected changes on the QRS duration and the QT interval. Four patients developed gastrointestinal symptoms (8.1%).



Oral quinidine was safe and effective in the conversion of persistent atrial fibrillation to sinus rhythm.