Rosacea – global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group

Background The absence of specific histological or serological markers, the gaps in understanding the aetiology and pathophysiology of rosacea, and the broad diversity in its clinical manifestations has made it difficult to reach international consensus on therapy guidelines. Objectives The main objective was to highlight the global diversity in current thinking about rosacea pathophysiology, classification and medical features, under particular consideration of the relevance of the findings to optimization of therapy. Methods The article presents findings, proposals and conclusions reached by the ROSacea International Expert group (ROSIE), comprising European and US rosacea experts. Results New findings on pathogenesis provide a rationale for the development of novel therapies. Thus, recent findings suggest a central role of the antimicrobial peptide cathelicidin and its activator kallikrein‐5 by eliciting an exacerbated response of the innate immune system. Cathelicidin/kallikrein‐5 also provide a rationale for the effect of tetracyclines and azelaic acid against rosacea. Clinically, the ROSIE group emphasized the need for a comprehensive therapy strategy – the triad of rosacea care – that integrates patient education including psychological and social aspects, skin care with dermo‐cosmetics as well as drug‐ and physical therapies. Classification of rosacea into stages or subgroups, with or without progression, remained controversial. However, the ROSIE group proposed that therapy decision making should be in accordance with a treatment algorithm based on the signs and symptoms of rosacea rather than on a prior classification. Conclusion The ROSIE group reviewed rosacea pathophysiology and medical features and the impact on patients and treatment options. The group suggested a rational, evidence‐based approach to treatment for the various symptoms of the condition. In daily practice this approach might be more easily handled than prior subtype classification, in particular since patients often may show clinical features of more than one subtype at the same time.     

Gastric and oesophageal emptying in insulin-dependent diabetes mellitus

Abstract Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 45 randomly selected insulin-dependent diabetics and in 22 control subjects. In the diabetics, the relationships between oesophageal emptying, gastric emptying, age, duration of diabetes mellitus, upper gastrointestinal symptoms, glycaemic control and the complications, autonomic neuropathy, peripheral neuropathy and retinopathy were examined. The lag period before solid food left the stomach was not significantly different in diabetics compared with control subjects, but the percentage retention of solid food at 100 min was greater ( P < 0.001) in the diabetic subjects. Both the early phase (percentage retention at 10 min) and the 50% emptying time for liquid gastric emptying were delayed ( P < 0.001) in the diabetic subjects. Of the diabetics, 58% had delayed gastric emptying of either the solid and/or the liquid meal; oesophageal emptying was delayed in 42%. Upper gastrointestinal symptoms correlated poorly with both gastric and oesophageal emptying. Oesophageal emptying, solid gastric emptying and the liquid 50% emptying time correlated with the severity of autonomic nerve dysfunction ( P < 0.05). The early phase of liquid emptying (retention at 10 min) was significantly slower ( P < 0.05) in patients with mean plasma glucose concentrations of > 15 mmol/l during the gastric emptying test and the lag period for solid emptying correlated with both the glycosylated haemoglobin and mean plasma glucose concentrations.     

Motor mechanisms associated with slowing of the gastric emptying of a solid meal by an intraduodenal lipid infusion

The aim of this study was to define better the motor phenomena associated with the slowing of gastric emptying by a duodenal lipid infusion. Antral, pyloric and duodenal motility were recorded in 10 healthy subjects with a manometric assembly which incorporated multiple perfused side-holes and a sleeve sensor positioned astride the pylorus. The gastric emptying of a standard solid meal and the distribution of the ingesta between the proximal and distal stomach were monitored with a radionuclide technique. A triglyceride emulsion was infused into the duodenum for 45 min once 25% of the meal had emptied. The infusion caused significant slowing in the rate of gastric emptying (P less than 0.01). This slowing in gastric emptying was associated with the suppression of pressure waves in the distal antrum (P less than 0.01) and proximal duodenum (P less than 0.01), the induction of pressure waves isolated to a narrow pyloric segment (P less than 0.01), and a redistribution of ingesta from the distal to proximal stomach. These findings suggest that pressure waves isolated to the pylorus, changes in the intragastric distribution of ingested food, and changes in proximal duodenal motility may all act in concert with changes in antral motility to regulate the gastric emptying of solids.     

Tc-99m TERTIARY BUTYL ISONITRILE: A PRELIMINARY CLINICAL STUDY OF A NEW MYOCARDIAL IMAGING AGENT IN PATIENTS WITH CHEST PAIN

Abstract Tc-99m is a preferred agent for nuclear imaging. Tc-99m tertiary butyl isonitrile (Tc-99m-TBI) is the first of a family of lipophilic cations which allow effective imaging of the human myocardium. Twenty-one patients scheduled for coronary angiography for the investigation of their chest pain were studied after injections of this tracer given during exercise, and on a separate visit, at rest. Despite high uptake in the liver and transiently in the lungs, high quality gated images were obtained allowing the assessment of both myocardial uptake and wall motion. The findings corresponded closely with angiographic and ventriculographic assessment of coronary artery disease and myocardial infarction. Redistribution of Tc-99m-TBI was shown to occur in ischemic myocardium analogous to that occurring with thallium-201 (TI-201). Similar agents with more favourable properties may well replace TI-201 as the myocardial imaging agent of choice in the near future.     

Exposure to dipeptidyl-peptidase-4 inhibitors and COVID-19 among people with type 2 diabetes: A case-control study

Because other coronaviruses enter the cells by binding to dipeptidyl-peptidase-4 (DPP-4), it has been speculated that DPP-4 inhibitors (DPP-4is) may exert an activity against severe acute respiratory syndrome coronavirus 2. In the absence of clinical trial results, we analysed epidemiological data to support or discard such a hypothesis. We retrieved information on exposure to DPP-4is among patients with type 2 diabetes (T2D) hospitalized for COVID-19 at an outbreak hospital in Italy. As a reference, we retrieved information on exposure to DPP-4is among matched patients with T2D in the same region. Of 403 hospitalized COVID-19 patients, 85 had T2D. The rate of exposure to DPP-4is was similar between T2D patients with COVID-19 (10.6%) and 14 857 matched patients in the region (8.8%), or 793 matched patients in the local outpatient clinic (15.4%), 8284 matched patients hospitalized for other reasons (8.5%), and when comparing 71 patients hospitalized for COVID-19 pneumonia (11.3%) with 351 matched patients with pneumonia of another aetiology (10.3%). T2D patients with COVID-19 who were on DPP-4is had a similar disease outcome as those who were not. In summary, we found no evidence that DPP-4is might affect hospitalization for COVID-19.     

牛津单髁膝关节置换：长期结果

牛津膝置换是使用最广泛的膝关节单髁置换（UKR）。牛津膝在37年前开始应用,拥有一个全匹配的活动衬垫,因而磨损率非常低。牛津膝最主要的使用指征是膝关节前内侧骨关节炎,这种病人至少占所有需要行膝关节置换术患者的50％。由于这一系统的设计特点,传统UKR的反指征,如年龄、活动量、肥胖、髌股关节损害和软骨钙质沉着症等对于牛津膝均不是反指征。与全膝关节置换（TKR）相比,牛津膝提供更快的康复、更好的功能、更大的活动度和更好的术后满意度,发生并发症更少、程度更轻,病残率和死亡率更低。一个持续超过30年的研究显示在90％的病例中,牛津膝为患者终生提供了优或良的临床结果,且不需要翻修。在最近15年,牛津膝通过微创手术入路植入,涉及6000多例使用该入路牛津膝置换的9个研究报道显示,10年生存率约95％。在许多这样的研究中,医生们在拟行膝关节置换的患者中约50％使用了牛津单髁膝置换。     

A longitudinal immunologic evaluation of hemophiliac patients

Over an average span of one year, we performed a prospective clinical and immunologic evaluation of 30 patients with hemophilia. No patient developed life-threatening opportunistic infection or malignancy; however, the immunologic abnormalities and lymphadenopathy initially present in nine patients (lymphadenopathy group) persisted. In addition, five patients, representing 24% of the initial group without lymphadenopathy, developed generalized lymphadenopathy (converter group). One episode of idiopathic thrombocytopenia (ITP) and one episode of staphylococcal sepsis occurred in this "converter" group; one episode of ITP also occurred in the lymphadenopathy group. Sixteen patients remained asymptomatic. At the time of the follow-up evaluation, those differences in mononuclear cell (MNC) percentages and numbers noted initially among the three hemophiliac groups were no longer present. Natural killer cell function alone or in the presence of biologic response modifiers was not different among hemophiliac and control groups. Before developing lymphadenopathy, the converter group of patients had significantly better lymphocyte mitogenic function than did the other two groups of patients with hemophilia. However, lymphocyte mitogenic responses of all groups of patients with hemophilia significantly deteriorated over the course of the study. The abnormal mitogenic responses noted in these patients was explained in part by higher levels of spontaneous suppressor cell activity in mononuclear cell preparations from patients with hemophilia. We conclude that long-term immunologic studies of this patient population requires both quantitative and qualitative evaluations. Our data show that patients with hemophilia have progressive dysfunction of cell- mediated immunity.     

Irresponsible responsibility

The Medical Association for Prevention of War (UK) submitted the following written statement to the Third Special Session on Disarmament of the United Nations General Assembly, which was held at UN headquarters in New York on 31 May‐25 June 1988.