Efficacy and safety of enteral supplementation with high-dose vitamin D in critically ill patients with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is associated with mortality and morbidity in critically ill patients. This study investigated the safety and effectiveness of enteral high-dose vitamin D supplementation in intensive care unit (ICU) patients in Asia. METHODS: This was a multicenter, prospective, randomized-controlled study. Eligible participants with vitamin D deficiency were randomly assigned to the control or vitamin D supplementation group. In the vitamin D supplementation group, the patients received 569,600 IU vitamin D. The primary outcome was the serum 25(OH)D level on day 7. RESULTS: 41 and 20 patients were included in the vitamin D supplementation and control groups, respectively. On day 7, the serum 25(OH)D level was significantly higher in the vitamin D supplementation group compared to the control group (28.5 [IQR: 20.2-52.6] ng/mL and 13.9 [IQR: 11.6-18.8] ng/mL, p < 0.001). Only 41.5% of the patients achieved serum 25(OH)D levels higher than 30 ng/mL in the supplementation group. This increased level was sustained in the supplementation group on both day 14 and day 28. There were no significant adverse effects noted in the supplementation group. Patients who reached a serum 25(OH)D level of >30 ng/mL on day 7 had a significantly lower 30-day mortality rate than did those who did not (5.9% vs 37.5%, p < 0.05). CONCLUSIONS: In our study, less than half of the patients reached adequate vitamin D levels after the enteral administration of high-dose vitamin D. A reduction in 30-day mortality was noted in the patients who achieved adequate vitamin D levels. TRIAL REGISTRATION CLINICALTRIALS. GOV ID: NCT04292873, Registered, March 1, 2020.

Questionnaire-Based Analysis of Adverse Events and Compliance with Malaria Chemoprophylaxis in Taiwan.

Malaria was eradicated in Taiwan in 1952; however, imported malaria cases are reported every year. The subtropical climate in Taiwan permits mosquito propagation and possible outbreaks of mosquito-borne diseases. The aim of this study was to investigate travelers' compliance and side effects of malaria prophylaxis to prevent a malaria outbreak in Taiwan. In this prospective study, we enrolled travelers who visited our travel clinic before going to malarious areas. A total of 161 questionnaires were collected and analyzed. Associations between the occurrence of side effects and compliance with antimalarial drugs were analyzed. Adjusted odds ratios were calculated after adjusting for potential risk factors in multiple logistic regression analysis. Of the 161 enrolled travelers, 58 (36.0%) reported side effects. Insomnia, somnolence, irritability, nausea, and anorexia were associated with poor compliance. Mefloquine was not associated with more neuropsychological side effects than doxycycline. Multiple logistic regression analysis showed that chemoprophylaxis compliance was affected by a younger age, visiting friends and relatives, visiting the travel clinic more than 1 week before the trip, and preferring to use the same antimalarial regimen on the next trip. Our findings could provide information to travelers besides labeled side effects to improve compliance with malaria prophylaxis and consequently help to prevent malaria outbreaks in Taiwan.

Inhibitory effect of phloretin on inflammation and oxidative stress in IL-1β induced orbital fibroblasts in Graves orbitopathy and its mechanism / 中华实验眼科杂志

Objective:To investigate the inhibitory effect of phloretin on inflammation and oxidative stress in interleukin (IL)-1β induced orbital fibroblasts (OFs) from Graves orbitopathy (GO) patients and its mechanism.Methods:The orbital fat and connective tissue from 6 eyes of 6 patients diagnosed as inactive GO who underwent orbital decompression in Henan Eye Hospital from January 2019 to December 2020 were collected.Primary OFs were isolated and passaged by explant culture and were identified by cell immunofluorescence assay.OFs were divided into control group, IL-1β induced group, and groups of various phloretin concentrations (25, 50, 75, 100 and 200 μmol/L). The viability of OFs after 24- and 48-hour treatment of the various phloretin concentrations was determined by cell counting kit-8 (CCK-8). OFs were induced by IL-1β to simulate an inflammatory environment of GO in vitro.Intracellular reactive oxygen species (ROS) levels of the normal control group, IL-1β induced group, 50 μmol/L phloretin group and 100 μmol/L phloretin group were detected by fluorescent probe (H 2DCF-DA). The concentrations of pro-inflammatory cytokines IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) in cell culture supernatant of the normal control group, IL-1β induced group and phloretin treated groups (25, 50, 75, and 100 μmol/L) were examined by enzyme-linked immunosorbent assay (ELISA). The expressions of heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2) proteins, as well as P38, extracelluar regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) proteins as well as their phosphorylated proteins in the MAPK signal pathway of the normal control group, IL-1β induced group and 100 μmol/L phloretin group, were detected by Western blot.The purpose and methods of the study were explained to the patients and their family members.Written informed consent was obtained.The study protocol was approved by the Ethics Committee of Henan Provincial People's Hospital (No.HNEECKY-2020[07]). Results:For cultured OFs, the mesenchymal origin was confirmed by positive expression of vimentin and fibroblasts were identified by negative expression of desmin, S-100 and cytokeratin-18.CCK-8 showed that there was no significant difference in absorbance value after 24- and 48-hour treatment between 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups and control group (all at P>0.05). The ROS levels of 50 μmol/L and 100 μmol/L phloretin groups were 21.95±1.71 and 10.01±1.03, respectively, which were significantly lower than 39.27±4.01 of IL-1β induced group (both at P<0.01). ELISA showed that IL-6 concentrations in 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups were (4 544.25±572.98), (1 000.25±133.96), (724.25±98.63), (519.50±118.02)pg/ml, respectively, which were all significantly lower than (7 581.75±565.93)pg/ml in IL-1β induced group (all at P<0.01). IL-8 concentrations in 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups were (3 679.50±676.76), (2 143.75±616.20), (1 174.75±284.18)pg/ml, respectively, which were all significantly lower than (8 411.00±939.67)pg/ml in IL-1β induced group (all at P<0.01). The concentrations of MCP-1 in 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups were (3 783.25±610.24), (1 565.75±457.89), (745.75±227.01)pg/ml, respectively, which were all significantly lower than (5 533.00±602.87)pg/ml in IL-1β induced group (all at P<0.01). The relative expression levels of HO-1 and Nrf2 were significantly higher and the relative expression levels of p-P38, p-ERK, and p-JNK were significantly lower in 100 μmol/L phloretin group than IL-1β induced group (all at P<0.01). Conclusions:Phloretin reduces the oxidative stress level of IL-1β induced OFs from GO patients and inhibits the production of pro-inflammatory cytokines.The mechanism is related to the activation of Nrf2/HO-1 and the inhibition of the MAPK signal pathway.

Affective Computing Based on Morphological Features of Photoplethysmography for Patients with Hypertension.

Negative and positive emotions are the risk and protective factors for the cause and prognosis of hypertension. This study aimed to use five photoplethysmography (PPG) waveform indices and affective computing (AC) to discriminate the emotional states in patients with hypertension. Forty-three patients with essential hypertension were measured for blood pressure and PPG signals under baseline and four emotional conditions (neutral, anger, happiness, and sadness), and the PPG signals were transformed into the mean standard deviation of five PPG waveform indices. A support vector machine was used as a classifier. The performance of the classifier was verified by using resubstitution and six-fold cross-validation (CV) methods. Feature selectors, including full search and genetic algorithm (GA), were used to select effective feature combinations. Traditional statistical analyses only differentiated between the emotional states and baseline, whereas AC achieved 100% accuracy in distinguishing between the emotional states and baseline by using the resubstitution method. AC showed high accuracy rates when used with 10 waveform features in distinguishing the records into two, three, and four classes by applying a six-fold CV. The GA feature selector further boosted the accuracy to 78.97%, 74.22%, and 67.35% in two-, three-, and four-class differentiation, respectively. The proposed AC achieved high accuracy in categorizing PPG records into distinct emotional states with features extracted from only five waveform indices. The results demonstrated the effectiveness of the five indices and the proposed AC in patients with hypertension.

Tongue and its ties: Posterior tongue width in gender estimation - A forensic gratuity.

BACKGROUND AND OBJECTIVES: Human identification is one of the challenging areas that man has been confronted with. The forensic odontologist deals with human identification based on unique features of the oral cavity. The human tongue is sheathed within the oral cavity, where it lies protected against the external atmosphere, just as the palatine folds. It is can be easily showed for inspection but at the same time be protected from the external environment. AIM AND OBJECTIVE: The objective of this study is to examine the uniqueness of tongue morphology and find out parameters to estimate gender of an individual using the same. METHODOLOGY: A total of 30 subjects (15 girls and 15 boys) were taken for this study whose tongue were examined, photographed and alginate impression were taken to create a database of tongue morphology. RESULT: The mean posterior width of the tongue was higher among the males in both cast as well as photographs.

Effect modification of hyperlipidemia and hypertension on the association between type 2 diabetes and gout.

AIMS: We evaluated the association between type 2 diabetes and gout by a retrospective cohort study. METHODS: Data of 17,259 male and 18,318 female patients with type 2 diabetes were retrieved for the 1998-2010 period. These patients were matched to a comparison group (n=34,518 and n=36,636, respectively) in a 1:2 ratio by age and region. RESULTS: We found that patients with type 2 diabetes after adjustment for hyperlipidemia and hypertension had a lower risk of incident gout than the matched population (incidence rate ratio, men: 0.39 [95% CI: 0.36-0.42]; women: 0.78 [0.72-0.84]). Specifically, type 2 diabetes alone without hyperlipidemia and hypertension was associated with a reduced risk of incident gout in men (adjusted relative risk [RR]: 0.29, 95% CI: 0.22-0.39), but not in women (0.86, 95% CI: 0.55-1.36). We found that insulin users with hyperlipidemia and hypertension associated with risk of incident gout and no sex-specific differences were noted (adjusted RR, men: 1.28 [95% CI: 1.11-1.48]; women: 1.32 [95% CI: 1.14-1.53]). Specifically, insulin users alone without hyperlipidemia and hypertension were not statistically significantly associated with gout risk (P≥.0954). CONCLUSIONS: The results of this study indicated that hyperlipidemia and hypertension modified the association between type 2 diabetes and gout.

Protective effect of a modified orbital decompression for postoperative eye position in thyroid-associated ophthalmopathy / 中华实验眼科杂志

Objective:To investigate the protective effect of a modified orbital decompression on postoperative eye position in thyroid-associated ophthalmopathy (TAO).Methods:A cohort study was performed.One hundred and thirty-six eyes of 96 TAO patients who received orbital decompression in Henan Eye Hospital from July 2008 to July 2018 were enrolled.The patients were divided into two groups according to different operation methods.A depressed bone window was made in the region of orbital apex in the modified orbital decompression group with 100 eyes of 70 patients.A depressed bone window was made in the middle and anterior region of orbit in the traditional orbital decompression group with 36 eyes of 26 patients.The best corrected visual acuity, palpebral fissure, eyeball exophthalmos, strabismus, eyeball position、CT image and postoperative complications were compared.This study was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2020[07]), and written informed consent was obtained from each subject before surgery.Results:Strabismus was improved in 14 eyes of 10 patients, unchanged in 75 eyes of 52 patients and slightly aggravated in 11 eyes of 8 patients after operation in the modified orbital decompression group.In the traditional orbital decompression group, strabismus was slightly aggravated in 6 eyes of 4 patients, seriously aggravated in 30 eyes of 22 patients after surgery. In the modified orbital decompression group, the eyeball displacement was unchanged in 91 eyes of 64 patients, slightly aggravated in 9 eyes of 6 patients after surgery in the traditional orbital decompression group, the eyeball displacement was slightly aggravated in 15 eyes of 10 patients, seriously aggravated in 21 eyes of 16 patients after surgery.Significant differences were found in the number of eyes with different degree of strabismus and eyeball displacement between the two groups ( Z=-9.634, -10.278, both at P<0.01). The postoperative eyeball exophthalmos values were (14.36±2.03)mm and (14.36±1.03)mm in the modified orbital decompression group and the traditional orbital decompression group, respectively, which were significantly lower than preoperative (20.47±1.92)mm and (20.28±2.03)mm (both at P<0.05). CT imaging showed that the bone window was clear in orbital apex and the compression of optic nerve was relieved postoperatively in the modified orbital decompression group, and the bone window was in anterior part of the orbit and the orbital apex was still crowded in the traditional orbital decompression group.No severe complication was seen during the fellow-up duration in the two groups. Conclusions:Compared with traditional orbital decompression, the modified orbital decompression surgery can reduce the risks of strabismus and eyeball displacement, showing an obvious protective effect on eye position.

Ocular lymphatic vascular malformation combined intracystic hemorrhage of surgical treatment / 中华整形外科杂志

Objective@#To discuss the radical treatment of lymphatic vascular malformation combined intracystic hemorrhage in Children.@*Methods@#66 cases with lymphatic vascular malformation combined intracystic hemorrhage were retrospectively analyzed. The longest diameter of all the lesions was nearly 4 cm.All the 66 patients received surgical treatment. Arc-shaped incision was made to separate and expose the eyes from the hair trace. The lesions were separated from the frontal and temporal parts to the eyes along the dermal fat layer, and deep separation revealed orbicularis oculi muscle and levator upper eyelid muscle.@*Results@#All the 66 cases were completely resected, and the patients were followed up for 0.5-3.0 years after the surgery. The postoperative appearance was satisfactory in 58 cases. The wound scar was healed in 8 cases, and the patients had satisfactory postoperative appearance after elective scar resection and cosmetic repair. Postoperative complications included long-term exudation of incision lymph in 6 cases. Among them, 4 cases were complicated with incision dehiscence and 2 cases were infected.@*Conclusions@#The method of complete resection of tumor as early as possible can radical cure the ocular lymphangioma with intracapsular hemorrhage, which prevent the disease from deteriorating, and meeting the aesthetic requirements of satisfactory appearance.

Predictors of smoking cessation in Taiwan: using the theory of planned behavior.

This study aimed to explore the factors predicting the intention to quit smoking and the subsequent behavior 6 months later using the theory of planned behavior (TPB). Data were obtained from 145 smokers who attended a smoking cessation clinic in a community hospital. All participants completed a questionnaire which included demographic information, TPB-based items, perceived susceptibility and previous attempts to quit. The actual quitting behavior was obtained by follow-up phone calls 6 months later. The TPB constructs explained 34% of the variance in intention to quit smoking. By adding perceived susceptibility, the explained variance was significantly improved to 40%. The most important predictors were perceived behavior control and perceived susceptibility, followed by attitude. Subjective norm did not contribute to the prediction of intention. Attitude and perceived behavior control contributed to the prediction of actual quitting behavior, but intention, subjective norm and perceived susceptibility did not. Our findings support that the TPB is generally a useful framework to predict the intention to quit smoking in Taiwan. The inclusion of perceived susceptibility improved the prediction of intention. With regards to successfully quitting, attitude and perceived behavior control played more crucial roles than other TPB constructs. Smoking cessation promotion initiatives focusing on reinforcing cessation belief, enhancing a smoker's perception of their capability to quit smoking, and persuading smokers that they can overcome cessation barriers to cessation could make subsequent interventions more effective.

Combined treatment with urea injection and surgical procedure for ocular arteriovenous malformation with fistula / 中华整形外科杂志

Objective@#To explore the treatment of the ocular arteriovenous malformation using urea injection combined with surgical procedures and evaluate clinical effects.@*Methods@#42 cases withocular arteriovenous malformation combined with fistula were retrospectively analyzed between January 2011 and December 2016. Individual treatments were formulated according to leision areas and severity. 3 cases with diffuse malformations were excluded from the study, because no surgical procedures were performed. 39 cases underwent local injection with 40% urea before resection. The urea was injected locally into vein malformation area by means ofmulti-point injection on a basis of 30 seconds, 3-6 ml for each treatment, once a day.The injection was performed for successive 7-10 days.The therapeutic effects and cosmetic result were recorded.@*Results@#23 cases occurred intheright ocular area and 16 cases in left.21 cases were removed radically in single operation.No recurrenceoccurredin any case with follow-ups of 3 months to 1.5 years.Cosmetic result with ocularbilateral symmetrywere satisfactory.@*Conclusions@#Combined treatment with urea injection and surgical procedure could effectively treat ocular arteriovenous malformation with arteriovenousfistula.

Detection of Galectin-3 in ocular venous malformation tissue and its clinical significance / 中华整形外科杂志

Objective@#To detect the expression level of Galectin-3 in the ocular Venous Malformation (VM) tissue, and explore its associations with the occurrence and development of ocular VM.@*Methods@#12 fresh ocular VM tissue samples and 12 simplex great saphenous vein varices tissue samples were collected. The mRNA and protein expression levels of Galectin-3 gene were detected by RT-PCR and Western Blot.@*Results@#The relative mRNA and protein levels of Galectin-3 in VM and control group were 5.26×10-3±8.78×10-4, 4.89×10-4±5.37×10-5 and 0.861±0.394, 0.223±0.206, respectively; Galectin-3 expressions in both mRNA and protein levels in ocular VM tissue were obviously higher than those in control group (P<0.05), and an increasing trend was accompanied with aggravating pathological changes in both degree and range of ocular VM.@*Conclusions@#Galectin-3 is highly expressed in ocular VM tissue in both mRNA and protein levels, which may be closely related to ocular VM development and prognosis, and can be used to determine the degree of local invasion of ocular VM. The pathogenesis of ocular VM may be related to Galectin-3, which can be further investigated through gene chip techniques.

Health-related quality of life and patient-reported outcomes of ofatumumab plus fludarabine and cyclophosphamide versus fludarabine and cyclophosphamide in the COMPLEMENT 2 trial of patients with relapsed CLL.

Chronic lymphocytic leukemia (CLL) is an incurable disease. Quality of life during treatment and periods of subsequent remission is therefore vital. Health-related quality of life (HRQoL) was compared in relapsed CLL during and after treatment with ofatumumab combined with fludarabine and cyclophosphamide versus fludarabine and cyclophosphamide alone. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 v3 and QLQ-CLL16 were used to assess HRQoL in this open-label, phase 3 study. Improvements in prespecified domains of patient-reported outcomes (Global Health Status [GHS]/HRQoL and B symptom scores) were recorded in both treatment arms after three cycles and were sustained after 18 months of follow-up. The two treatment arms were not significantly different at the nominal 0.05 level for GHS/HRQoL (p = .7278) or B symptoms (p = .5968). Small improvements in quality of life were maintained after therapy. The addition of ofatumumab was without any adverse impact on HRQoL (NCT00824265).

Ofatumumab plus fludarabine and cyclophosphamide in relapsed chronic lymphocytic leukemia: results from the COMPLEMENT 2 trial.

In this multicenter, open-label, phase III study, patients with relapsed chronic lymphocytic leukemia (CLL) were randomized (1:1) to receive ofatumumab plus fludarabine and cyclophosphamide (OFA + FC) or FC alone; the primary endpoint being progression-free survival (PFS) assessed by an independent review committee (IRC). Between March 2009 and January 2012, 365 patients were randomized (OFA + FC: n = 183; FC: n = 182). Median IRC-assessed PFS was 28.9 months with OFA + FC versus 18.8 months with FC (hazard ratio = 0.67; 95% confidence interval, 0.51-0.88; p = .0032). Grade ≥3 adverse events (≤60 days after last dose) were reported in 134 (74%) OFA + FC-treated patients compared with 123 (69%) FC-treated patients. Of these, neutropenia was the most common (89 [49%] vs. 64 [36%]). OFA + FC improved PFS with manageable safety for patients with relapsed CLL compared with FC alone, thus providing an alternative treatment option for patients with relapsed CLL. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00824265).

Health-related quality of life and patient-reported outcomes of ofatumumab plus chlorambucil versus chlorambucil monotherapy in the COMPLEMENT 1 trial of patients with previously untreated CLL.

BACKGROUND: Patients diagnosed with chronic lymphocytic leukemia (CLL) are usually elderly and frequently have a number of comorbidities. Health-related quality of life (HRQoL) for these patients is of utmost importance and should be taken into consideration when assessing new treatment options. The combination of ofatumumab with chlorambucil has shown longer progression-free survival compared with chlorambucil alone. In this study, we aim to assess how this treatment combination affects patients' health-related quality of life and patient-reported symptoms. MATERIAL AND METHODS: In this open-label phase III trial, patients with previously untreated CLL for whom fludarabine-based treatment was contra-indicated, were randomized 1:1 to receive oral chlorambucil (10 mg/m2) on Days 1-7 of a 28-day treatment cycle or to receive chlorambucil by this schedule plus intravenous ofatumumab (Cycle 1: 300 mg on Day 1 and 1000 mg on Day 8; subsequent cycles: 1000 mg Day 1) for 3-12 cycles. The EORTC QLQ-C30 and QLQ-CLL16 questionnaires were administered to patients before and during treatment, in follow-up and at the time of disease progression. The primary specified patient-reported outcomes were HRQoL and fatigue. RESULTS: Patient-reported improvements from baseline in Global Health Status (GHS)/HRQoL scores and fatigue scores were recorded during treatment with both chlorambucil monotherapy and ofatumumab in combination with chlorambucil. There were no significant differences between the two treatment arms for GHS/HRQoL (p = 0.667) or fatigue (p = 0.103). Following treatment, numerical improvements to GHS/HRQoL and fatigue scores were reported, with no significant differences between the two treatment arms. CONCLUSION: Small but detectable improvements in patients' quality of life were reported as a result of treatment. The addition of ofatumumab to chlorambucil did not negatively impact HRQoL. Quality of life was maintained in the months following treatment.

Statin use after intracerebral hemorrhage: a 10-year nationwide cohort study.

INTRODUCTION: Although statin therapy is beneficial to patients with ischemic stroke, statin use, and intracerebral hemorrhage (ICH) remain a concern. ICH survivors commonly have comorbid cardiovascular risk factors that would otherwise warrant cholesterol-lowering medication, thus emphasizing the importance of assessing the characteristics of statin therapy in this population. METHODS: We performed a cohort study by using 10 years of data collected from the National Health Insurance Research Database in Taiwan. We enrolled 726 patients admitted for newly diagnosed ICH from January 1, 2001 to December 31, 2010. The patients were categorized into high- (92), moderate- (545), and low-intensity (89) statin groups, and into hydrophilic (295) and lipophilic (431) statin groups. The composite outcomes included all-cause mortality, recurrent ICH, ischemic stroke, transient ischemic attack, and acute coronary events. RESULTS: The patients in the low-intensity group did not differ significantly from the patients in the high-intensity group in risk of all-cause mortality (adjusted hazard ratio [aHR] = 0.65, 95% confidence interval [CI] = 0.28-1.55) and recurrent ICH (aHR = 0.66, 95% CI = 0.30-1.44). In contrast, the patients in the hydrophilic group had a significantly lower risk of recurrent ICH than did those in the lipophilic group (aHR = 0.69, 95% CI = 0.48-0.99). We determined no significant differences in other composite endpoints between hydrophilic and lipophilic statin use. CONCLUSION: Hydrophilic statin therapy is associated with a reduced risk of recurrent ICH in post-ICH patients. The intensity of statin use had no significant effect on recurrent ICH or other components of the composite outcome. Additional studies are required to clarify the biological mechanisms underlying these observations.

A phase 2, multicenter study investigating ofatumumab and bendamustine combination in patients with untreated or relapsed CLL.

The purpose of this study is to assess the safety and efficacy of the combination of ofatumumab and bendamustine in patients with previously untreated or relapsed chronic lymphocytic leukemia. Patients received IV ofatumumab (cycle 1: 300 mg day 1 and 1,000 mg day 8; cycles 2-6: 1,000 mg on day 1 every 28 days) and IV bendamustine 90 mg m(-2) (previously untreated) or 70 mg m(-2) (relapsed) on days 1 and 2 of each 28-day cycle, for up to 6 cycles. Forty-four previously untreated and 53 relapsed patients were enrolled. Median age was 62.5 years (previously untreated) and 68 years (relapsed); relapsed patients had received a median of 1 (range 1-11) prior therapy. The investigator-assessed overall response rate was 95% (43% complete response [CR]) for the previously untreated, and 74% (11% CR) for the relapsed patients. The regimen was well tolerated with 89% (previously untreated) and 85% (relapsed patients) receiving all 6 cycles. No unexpected toxicities were reported. Grade 3/4 events occurred in 57% of previously untreated, and 72% of relapsed patients. At ∼29 months' follow-up, the median progression-free survival (PFS) was not reached for the previously untreated population, and the 28-month PFS estimate was 72.3%. The median PFS for the relapsed population was 22.5 months (95% CI: 14.0-27.3 months). The combination of ofatumumab and bendamustine was well tolerated and effective in these previously untreated or relapsed populations. Am. J. Hematol. 91:900-906, 2016. © 2016 Wiley Periodicals, Inc.

Intracellular lipid dysregulation interferes with leukocyte function in the ovaries of meat-type hens under unrestricted feed intake.

Meat-type Red-feather country hens fed ad libitum (AD-hens) exhibit obesity-associated morbidities and a number of ovarian irregularities. Leukocyte participations in ovarian activities are unstudied in AD-hens. In contrast to feed-restricted hens (R-hens), ovulatory process of the F1 follicle appeared delayed in AD-hens in association with reduced F1 follicle progesterone content, gelatinase A (MMP-2) and collagenase-3 (MMP-13) activities coincident with elevated IL-1ß and no production (P<0.05), and increased leukocyte infiltration of inflamed necrotic follicle walls. Extracts of AD-hen F1 follicle walls induced greater leukocyte migration than extracts from F1 follicle wall extracts of R-hens (P<0.05). Co-cultures of granulosa cells with increasing numbers of leukocytes from either AD-hens or R-hens exhibited dose dependent reductions in progesterone production and increases in cell death. AD-hen leukocytes were less proapoptotic than their R counterparts (P<0.05). Granulosa MMP-13 and MMP-2 activities were also suppressed in the co-cultures with heterophils or monocytes in a dose-dependent manner (P<0.05). AD heterophils and R monocytes had a greater inhibitory effect on MMP activities in the co-cultures than their respective counterparts (P<0.05). Both basal and LPS-induced IL-1ß secretion and MMP-22 or MMP-2 activities in freshly isolated AD-hen leukocytes were reduced (P<0.05). Exposure of AD or R leukocytes to 0.5mM palmitate impaired IL-1ß secretion and MMP-22 or MMP-2 activity. Inhibition of ceramide synthesis with FB1 and ROS production with n-MPG scavenging rescued MMP activity and IL-1ß production in palmitate treated heterophils, but exacerbated monocyte suppression. These latter findings suggest that intracellular lipid dysregulation in leukocytes contributes to ovarian dysfunction in AD-hens.

Phase III, randomized study of ofatumumab versus physicians' choice of therapy and standard versus extended-length ofatumumab in patients with bulky fludarabine-refractory chronic lymphocytic leukemia.

We report results of a randomized, phase III study of ofatumumab versus physicians' choice treatment in patients with bulky fludarabine-refractory chronic lymphocytic leukemia and explore extended versus standard-length ofatumumab treatment. Patients (79 ofatumumab, 43 physicians' choice) completed a median 6 (ofatumumab) or 3 (physicians' choice) months' therapy. Ofatumumab-treated patients with stable disease or better were randomized (2:1) to 6 months' extended ofatumumab treatment or observation. Although the study did not meet the primary endpoint of progression-free survival (PFS) by independent review committee (ofatumumab: 5.4 months, physicians' choice: 3.6 months; p = 0.27), median PFS by investigators was significantly longer for ofatumumab versus physicians' choice (7.0 versus 4.5 months; p = 0.003) as was time to next therapy (median 11.5 versus 6.5 months; p = 0.0004). PFS and time to next therapy were significantly longer with ofatumumab extended treatment than observation (p = 0.026 and p = 0.002, respectively; n = 37). The adverse-event profile of long-term ofatumumab administration showed no unexpected findings (Clinicaltrials.gov identifier: NCT01313689).

Correlation betw een the etiologic subtype and outcome in patients w ith non -disabling ischemic cerebrovascular events / 国际脑血管病杂志

ObjectiveToinvestigatethecorrelationbetweentheetiologicsubtypeandoutcomein patients w ith non-disabling ischemic cerebrovascular events (NICE). Methods The consecutive patients w ith NICE admitted to hospital within 7 days after onset were enroled prospectively and folowed for 90 days. Etiologic subtypes w ere classified according to the Chinese Ischemic Stroke Subclassification (CISS). Good outcome w as defined as modified Rankin Scale score 0-2. Multivariate logistic regression analysis w as used to identify the independent risk factors for stroke recurrence and poor outcomes. Results A total of 162 patients with NICE were enroled. According to CISS, 76 (46.9%) were classified into large artery atherosclerosis (LAA), 54 (33.3%) into penetrating artery disease (PAD), 15 (9.3%) into cardiogenic stroke (CS), 11 (6.8%) into undetermined etiology (UE), and 6 (3.7%) into other etiology (OE). A total of 30 patients (18.5%) had recurrent stroke w ithin 90 days and 42 (25.9%) had poor outcomes. The proportions of patients w ith diabetes (46.7%vs.20.5%;χ2 =8.885, P=0.003), previous stroke or transient ischemic attack (46.7%vs.25.0%;χ2 =5.572, P=0.018), CS (20.0%vs.6.8%;Fisher exact test:P=0.036) in the stroke recurrence group w ere significantly higher than those in the non-stroke recurrence group, and the proportion of PAD patients in the stroke recurrence group w as significantly low er than that in the non -stroke recurrence group ( 16.7%vs.37.1%; χ2 =4.602, P=0.032 ). Multivariate logistic regression analysis show ed that diabetes (odds ratio [OR] 2.137, 95%confidence interval [CI] 1.359-4.187;P=0.004) and CS (OR 5.236, 95%CI 2.326-10.256; P<0.001) w ere the independent risk factors for recurrent stroke of NICE. The proportions of patients w ith hypertension ( 83.3%vs.61.7%; χ2 =6.635, P=0.010 ), diabetes (40.5%vs.20.0%;χ2 =6.900, P=0.009), atrial fibrilation (35.7%vs.14.2%;χ2 =9.113, P=0.003) and CS ( 19.0%vs.5.8%; Fisher exact test: P= 0.017 ) in the poor outcome group w ere significantly higher than those in the good outcome group, and the proportion of PAD patients ( 16.7%vs. 39.2%;χ2 =7.088, P=0.008) in the poor outcome group w as significantly low er than that in the good outcome group. Multivariate logistic regression analysis show ed that diabetes ( OR 2.257, 95%CI 1.209-3.687; P=0.010), atrial fibrilation (OR 3.137, 95%CI 1.359-6.107, P=0.002), and CS (OR 6.123, 95%CI 2.026-12.256, P<0.001) w ere the independent risk factors for poor outcomes in patient w ith NICE. Conclusions The etiologic subtype is associated w ith the poor outcomes and recurrent stroke, and can provide reference for recurrence and clinical outcome assessment in patients w ith NICE.

Systemic and local bactericidal potentiality in late lactation Holstein-Friesian cows following a combined antibiotics and Enterococcus faecium SF68 dry-cow treatment.

Antibiotic dry-cow treatment contributes a major part to the total use of antibiotics in dairy herds. Enterococcus faecium strain SF68 (SF68) was of human origin but has been authorized in EU as probiotic feed additive. In the present study, one of the front and rear quarters of twelve late lactation Holstein-Friesian cows were infused once with a commercial antibiotic dry-cow formula (antibiotics quarter) on the first milk-stasis day (d 1), when the contrallateral quarters were infused with 5 x 10(8)-CFU SF68 plus half-dose antibiotic dry-cow formula (SF68/antibiotics quarter) meanwhile. Gelatinase level and cellular reactive oxygen species (ROS) production capacity were measured for blood and quarter secretion. The results showed that the count of blood total leukocytes minorly decreased on d 3 only but the microscopic somatic cell count (MSCC) continuously increased up to d 7, especially in SF68/antibiotics quarters. Plasma level of gelatinase A remained similar up to d 7 but gelatinase B was not detectable in plasma throughout the study. The level of gelatinase A in quarter secretion increased up to d 7 but gelatinase B increased even more drastically, especially in SF68/antibiotics quarters. The ROS production capacity of blood leukocytes increased temporarily only on d 3, but that of milk cells continuously increased up to d 7, especially in SF68/antitiotics quarters. Overall, late lactation Holstein-Friesian cows were systemically adaptable to the combined antibiotics and SF68 dry-cow treatment, while the local bactericidal potentiality in mammary gland was actively responsive to additional SF68 intramammary treatment.