Somatostatin and insulin secretion from pancreatic islets: studies on the effect of high K+, 9-aminoacridine and valinomycin

We attempted to determine whether a decrease in the potassium permeability of the D cell membrane plays a role in the stimulus-secretion coupling, as it does in the pancreatic B cell. Elevation in the extracellular potassium concentration from 5.5 to 16.5 mM, or 0.2 mM 9-aminoacridine, which decreases potassium permeability in plasma membrane, stimulated the release of somatostatin as well as insulin from the isolated rat pancreatic islets. Valinomycin (1 microM), a potassium ionophore inhibited the secretion in response to high glucose, high extracellular potassium or 9-aminoacridine. These findings indicate that a reduction in potassium permeability in the D cell membrane, as induced by glucose or other stimulants, may be a major step in secretion of somatostatin.     

Efficacy of second generation antipsychotics in treating acute mixed episodes in bipolar disorder: A meta-analysis of placebo-controlled trials

Background

The literature on the treatment mixed episodes in Bipolar Disorder [BD] is sparse. Second generation antipsychotics [SGA] have documented efficacy in mania, but not mixed episodes. The objective of this meta-analysis was to ascertain the efficacy of SGA, either as mono- and/or adjunctive therapy, in the treatment of acute mixed episodes of BD, compared to placebo.

Methods

A MEDLINE search for English language publications of randomized controlled trials [RCTs] comparing SGA with placebo in the treatment of an acute manic/mixed episode of BD, during the period 1990–2012, was performed using the terms ‘atypical antipsychotics’, ‘SGA’, ‘mixed episodes’, ‘dysphoric mania’ and each SGA independently. 9 RCTs reporting data on 1289 mixed episode patients treated with aripiprazole, asenapine, olanzapine, paliperidone-ER, risperidone, and ziprasidone, either as monotherapy or as adjunctive therapy, versus placebo, for 3–6 weeks, were included in the meta-analysis. We extracted data on the number of patients, SGA, duration of study and mean change in mania and depression scores from baseline to endpoint. Standardized mean difference between SGA and placebo for the mean baseline-to-endpoint change in mania and depression rating scores was calculated, with a 95% confidence limit.

Results

SGA, either alone or in combination with mood stabilizers, had superior efficacy in treating manic symptoms of mixed episodes compared to placebo (−0.41, 95% CI −0.53, −0.30; overall effect p<0.00001). SGA were equally effective for manic symptoms in mixed episodes and pure mania (p=0.99). SGA had superior efficacy in treating depressive symptoms of mixed episodes (−0.30, 95% CI −0.47, −0.13; p<0.001) compared to placebo in two trials reporting this information.

Limitations

Thirteen relevant studies could not be included as data for mixed-episodes were not presented separately.

Conclusions

SGA are effective in treating acute mixed episodes of BD, with predominant manic symptoms. Their efficacy in treating depressed mixed episodes remains unclear.     

Physician communication styles in initial consultations for hematological cancer

Objective

To characterize practices in subspecialist physicians’ communication styles, and their potential effects on shared decision-making, in second-opinion consultations.

Methods

Theme-oriented discourse analysis of 20 second-opinion consultations with subspecialist hematologist-oncologists.

Results

Physicians frequently “broadcasted” information about the disease, treatment options, relevant research, and prognostic information in extended, often-uninterrupted monologs. Their communicative styles had one of two implications: conveying options without offering specific recommendations, or recommending one without incorporating patients’ goals and values into the decision. Some physicians, however, used techniques that encouraged patient participation.

Conclusions

Broadcasting may be a suboptimal method of conveying complex treatment information in order to support shared decision-making. Interventions could teach techniques that encourage patient participation.

Practice implications

Techniques such as open-ended questions, affirmations of patients’ expressions, and pauses to check for patient understanding can mitigate the effects of broadcasting and could be used to promote shared decision-making in information-dense subspecialist consultations.     

COVID-19 associated mucormycosis (CAM) in India: a formidable challenge

Together with the ongoing serious COVID-19 second wave in India, a serious fungal infection, mucormycosis has been increasingly found in COVID-19-recovered patients. Colloquially known as ‘black fungus’, mucormycosis commonly causes necrosis in the head and neck including the nose, paranasal sinuses, orbits, and facial bones, with possible intracranial spread. The disease causes high morbidity and mortality given that it progresses rapidly and diagnosis is often delayed. Given the sheer magnitude of the outbreak, the Indian Health Ministry has advised all states to declare mucormycosis an epidemic. Typically, the disease has been found to be linked to COVID-19 infections caused by the B.1.617.2 (Delta) variant, which has spread rapidly throughout the country. This variant has already become a cause for global concern, having spread to at least 40 countries, including the USA and UK. We present the findings of a study conducted on COVID-19 associated mucormycosis (CAM) patients, and discuss the associated risk factors to raise awareness for OMFS colleagues.     

三级医院护士第二受害者效应现状调查及影响因素分析

目的调查三级医院护士经历不良事件后的第二受害者效应现状,并分析其影响因素。方法本研究为横断面调查研究,采用便利抽样方法于2019年10—12月选取北京市、山西省、山东省三级医院护士作为调查对象,采用一般资料调查表、第二受害者经历与支持测评量表对其进行调查。通过单因素方差分析、多重线性回归分析对护士第二受害者影响因素进行分析。共发放网络问卷2163份,有效回收2040份,有效回收率为94.3%。结果813名护士报告了不良事件经历,纳入研究分析。813名护士第二受害者效应总分为(58.01±15.32)分,各维度条目均分中,“心理困扰”得分最高,“管理支持”得分最低,分别为(3.20±1.04)分和(2.02±0.90)分。单因素分析结果显示,不同科室、婚姻状态、职称和用工性质的护士第二受害者效应总分比较,差异有统计学意义(P<0.05);多重线性回归分析结果显示,科室、职称、用工性质是护士第二受害者效应的影响因素;用工性质、婚姻状态、科室对第二受害者生理困扰有影响;不良事件分级和科室对第二受害者心理困扰有影响。结论不良事件的发生对三级医院护士第二受害者的影响处于中等水平,护士所面临的心理困扰较严重,感受到的支持主要依靠“管理支持”,并受到多因素影响。医院管理者应积极看待第二受害者效应,关注经历第二受害者角色护士的身心健康,并针对不同的影响因素提供有效的支持。     

Mandibular dental changes following serial and late extraction of mandibular second premolars

Objectives:To determine changes in occlusal curves and dental tipping occurring from mandibular second premolar serial extraction, early extraction of deciduous mandibular second molars with missing second premolars, and late second premolar extraction compared with untreated controls.Materials and Methods:Information was collected from 85 subjects at three time points: T0, prior to serial extraction; T1, after serial extraction and drift prior to orthodontic treatment, and pretreatment for the late premolar extraction patients; and T2, posttreatment. Untreated age- and gender-matched controls were used for comparison. Three occlusal curves were measured on digitized mandibular casts, and dental tipping was assessed using lateral cephalograms.Results:At T0, there were no significant differences among groups. At T1, there was significant steepening of Monson''s sphere and the curve of Wilson between early and late extraction and control groups. At T2, the differences in Monson''s sphere and the curve of Wilson were fully corrected. At T1, there were significant differences in the tipping of mandibular 6''s, 4''s, and 3''s between the early extraction groups compared with the late extraction and control groups. At T2, these differences in tipping were fully corrected. There were no differences in mandibular incisor tipping between groups at T1 or T2.Conclusions:Serial extraction produced steeper occlusal curves and significant tipping of mandibular first molars, first premolars, and canines after extraction and physiologic drift (T1). Accentuated occlusal curves and tooth tipping were fully corrected following orthodontic treatment (T2). Mandibular incisor position was unchanged by serial or late second premolar extraction.     

Unmanipulated Reduced-Intensity Stem Cell Transplantation from a Haploidentical Donor Mismatched at 3 HLA Antigens to a Patient with Leukemic Transformation of Myelodysplastic Syndrome: Successful Second Transplantation after Graft Rejection

We present the case of a patient with myelodysplastic syndrome who experienced leukemia transformation and subsequently underwent transplantation of unmanipulated peripheral blood stem cells from a haploidentical sibling mismatched at 3 HLA antigens, along with a reduced-intensity regimen (fludarabine, busulfan, and anti-T-lymphocyte globulin) and tacrolimus-containing graft-versus-host disease (GVHD) prophylaxis. The patient experienced graft rejection but successfully underwent a second transplantation from the same donor with a slightly intensified conditioning regimen. Although the patient developed life-threatening cytomegalovirus (CMV) pneumonia following the second transplantation, he recovered completely from the pneumonia with intensive supportive therapy. He is still in complete remission past day 1000 in the absence of GVHD. As far as we know, this report is the first to describe a successful second transplantation that was performed for graft rejection following HLA-haploidentical nonmyeloablative stem cell transplantation. Furthermore, we emphasize that patients should be carefully monitored for CMV infection when reduced-intensity conditioning is given repeatedly over a short period.     

Impact of the supine position versus left horizontal position on colonoscopy insertion: a 2-center,randomized controlled trial

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超声引导下胎儿心肌壁注射KCl在KCl减胎术中的应用效果

目的 探讨超声引导下胎儿心肌壁注射氯化钾（KCl）在中孕期双绒毛膜双羊膜囊双胎妊娠KCl减胎术中的手术效果。方法 回顾性分析2017年9月至2020年1月安徽医科大学第一附属医院收治的因中孕期双绒毛膜双羊膜囊双胎妊娠伴有双胎之一异常行KCl减胎术的27例孕妇临床资料。根据术中KCl注射部位不同将研究对象分为心腔内注射组（超声引导下胎儿心腔内注射KCl）13例及心肌壁注射组（超声引导下胎儿心肌壁注射KCl）14例。比较两组手术时间、KCl用量和围产儿结局的差异。结果 心腔内注射组手术时间为（33.69±2.46）min,长于心肌壁注射组的（19.86±1.51）min,差异有统计学意义（P<0.05）;心腔内注射组KCl用量为（6.00±0.71）mL,多于心肌壁注射组的（2.79±0.54）mL,差异有统计学意义（P<0.05）;分娩28天后电话随访,两组孕妇的分娩孕周及新生儿体质量比较,差异均无统计学意义（P>0.05）。结论 在中孕期KCl减胎术中,心肌壁注射KCl较传统的心腔内注射KCl手术耗时更少,KCl用量更少,且不影响保留胎儿的分娩孕周及新生儿出生体质量。     

FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer: A subset analysis of data from a nationwide multicenter observational study in Japan

BackgroundData on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study—a nationwide, multicenter, observational study—FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice.MethodsWe performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings.ResultsOf the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients’ characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2–19.1) months and 6 cycles (range, 1–13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2–13.3), 4.1 (95% CI, 2.6–5.5) months, and 30%, respectively.ConclusionOur findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment.