Letter to the Editor: Reverse T3;a Reliable Diagnostic Test for Discerning between Euthyroid Sick and Central Hypothyroidism

Letter to the Editor.

Efficacy of rituximab in gastric diffuse large B cell lymphoma patients

AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[scheduled as cyclophosphamide,doxorubicin,vincristine and prednisone (CHOP)and CHOP-like],and chemotherapy combined with rituximab(group B,n=30).The primary end point of the study was complete response(CR)rate;the secondary end points were disease-free survival (DFS)at 5 years and overall survival(OS).RESULTS:Median follow-up was 62 mo(range:31102 mo).We observed a significant difference between the two groups(A vs B)in terms of CR[76.6%(23/30) vs 100%,P=0.04)and DFS at 5 years[73.3%(22/30) vs 100%,P=0.03).To date,19 group A(63.3%) patients are alive and 11 have died,while all group B patients are alive.No significant differences in toxicity were observed between the two groups.CONCLUSION:Rituximab in combination with chemotherapy improves CR rate,DFS and OS.Further prospective trials are needed to confirm our results.

Primary leiomyosarcoma of the thyroid gland with prior malignancy and radiotherapy:A case report and review of literature

BACKGROUND Leiomyosarcoma(LMS) of the thyroid gland is a rarely presented tumor that offers poor prognosis. To the best of the authors' knowledge, there currently exist only 28 known cases described in the literature(limited to English).CASE SUMMARY Herein a case is reported of a 60-year-old female patient who had an LMS of the thyroid, which was accompanied by periodic dysphonia and breathing disorder as well as the feeling of pressure in the chest and neck. At the time the disease was diagnosed, no metastases were detected. Prior to the diagnosis, the patient experienced a uterine adenocarcinoma that had been treated by surgical procedure and radiotherapy. For the LMS, a total thyroidectomy was performed,followed by radiotherapy. Since metastases were also discovered in the lungs,sternum, and femur, chemotherapy was administered as well.Immunohistochemically, the tumor cells in the thyroid indicated positively for alpha smooth muscle actin, calponin, and H-caldesmon, but were negative for CD34, p63, estrogen receptor, progesterone receptor, and Epstein-Barr virus.CONCLUSION Although the etiology of the LMS is as of yet unknown, prior malignancy and radiation should be considered as risk factors.

甲状腺细针吸取细胞学检查的临床应用价值(英文)

Objective:The aim of the study was to investigate the diagnostic value of fine needle aspiration cytology (FNAC) and its clinical application.Methods:From April 2009 to February 2011,thyroid FNAC were performed in a total of 186 patients with thyroid nodule or mass in our hospital and 78 of those 186 patients subsequently underwent thyroidectomy.The FNAC findings were compared with the results of the corresponding histological diagnosis.Results:The results of thyroid FNAC for 186 patients showed that,(1) 166 cases of benign lesions,the detection rate was 89.24% (166/186),including 96 cases of nodular colloid goiter (51.61%),28 cases of simple colloid goiter (15.05%),38 cases of Hashimoto's thyroiditis (HT) (20.43%) and 4 cases of thyroid adenoma (2.15%);(2) 4 cases of suspicious malignant lesion,the detection rate was 2.15% (4/186);(3) 16 cases of malignant tumor,the detection rate was 8.60% (16/186).Seventy eight patients including malignant (16),suspicious malignant (4),HT (20) and nodular colloid goiters (38) cases diagnosed by FNAC were performed operation with thyroidectomy and the postoperative histopathologic results showed that there were 2 cases HT combined thyroid papillary carcinoma in HT 20 cases by FNAC,15 cases of thyroid papillary carcinoma and 1 case of follicular carcinoma in 16 cases of malignant tumor by FNAC and 4 case of thyroid papillary carcinoma in 4 cases of suspicious malignant by FNAC.Conclusion:Thyroid FNAC is a valuable and reliable method for the diagnosis of the thyroid nodules or mass or even most diffuse thyroid diseases.Diagnosis of HT and thyroid papillary carcinoma can be made by thyroid FNAC.There was larger hint value for nodular colloid goiter and simple colloid goiter according to thyroid FNAC.

Digital single-operator video cholangioscopy improves endoscopic management in patients with primary sclerosing cholangitis-a retrospective observational study

BACKGROUND Patients with primary sclerosing cholangitis(PSC)are at a high risk of developing cholestatic liver disease and biliary cancer,and endoscopy is crucial for the complex management of these patients.AIM To clarify the utility of recently introduced digital single-operator video cholangioscopy(SOVC)for the endoscopic management of PSC patients.METHODS In this observational study,all patients with a history of PSC and in whom digital SOVC(using the SpyGlass DS System)was performed between 2015 and 2019 were included and retrospectively analysed.Examinations were performed at a tertiary referral centre in Germany.In total,46 SOVCs performed in 38 patients with a history of PSC were identified.The primary endpoint was the evaluation of dominant biliary strictures using digital SOVC,and the secondary endpoints were the performance of selective guidewire passage across biliary strictures and the diagnosis and treatment of biliary stone disease in PSC patients.RESULTS The 22 of 38 patients had a dominant biliary stricture(57.9%).In 4 of these 22 patients,a cholangiocellular carcinoma was diagnosed within the stricture(18.2%).Diagnostic evaluation of dominant biliary strictures using optical signs showed a sensitivity of 75%and a specificity of 94.4%to detect malignant strictures,whereas SOVC-guided biopsies to gain tissue for histopathological analysis showed a sensitivity of 50%and a specificity of 100%.In 13%of examinations,SOVC was helpful for guidewire passage across biliary strictures that could not be passed by conventional methods(technical success rate 100%).Biliary stone disease was observed in 17.4%of examinations;of these,in 37.5%of examinations,biliary stones could only be visualized by SOVC and not by standard fluoroscopy.Biliary stone treatment was successful in all cases(100%);25%required SOVC-assisted electrohydraulic lithotripsy.Complications,such as postinterventional cholangitis and pancreatitis,occurred in 13%of examinations;however,no procedure-associated mortality occurred.CONCLUSION Digital SOVC is effective and safe for the endoscopic management of PSC patients and may be regularly considered an additive tool for the complex endoscopic management of these patients.

Ursodeoxycholic acid as a means of preventing atherosclerosis,steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

BACKGROUND Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of mortality in patients with nonalcoholic fatty liver disease(NAFLD).Weight loss is a key factor for successful NAFLD and CVD therapy.Ursodeoxycholic acid(UDCA),which is one of the first-line therapeutic agents for treatment of NAFLD,is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIM To evaluate the effects of 6 mo of UDCA treatment on hepatic function tests,lipid profile,hepatic steatosis and fibrosis,atherogenesis,and ASCVD risk in men and women with NAFLD,as well as to assess the impact of>5%weight reduction on these parameters.METHODS An open-label,multicenter,international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise.The efficacy criteria were liver enzymes,lipid profile,fatty liver index(FLI),noninvasive liver fibrosis tests(nonalcoholic fatty liver disease fibrosis score and liver fibrosis index),carotid intima-media thickness(CIMT),and ASCVD risk score.To test statistical hypotheses,the Wilcoxon test,paired t-test,Fisher’s exact test,and Pearson's chi-squared test were used.RESULTS The alanine aminotransferase(ALT)level changed by-14.1 U/L(-31.0;-5.3)from baseline to 3 mo and by-6.5 U/L(-14.0;0.1)from 3 to 6 mo.The magnitude of ALT,aspartate transaminase,and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo(P<0.001,P<0.01,P<0.001,respectively).At 6 mo,in the total sample,we observed a statistically significant decrease in body weight and levels of FLI:84.9±10.4 vs 72.3±17.6,P<0.001,total cholesterol:6.03±1.36 vs 5.76±1.21,Р<0.001,lowdensity lipoprotein:3.86±1.01 vs 3.66±0.91,Р<0.001,and triglyceride:3.18(2.00;4.29)vs 2.04(1.40;3.16),Р<0.001.No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found.The CIMT decreased significantly in the total sample(0.985±0.243 vs 0.968±0.237,P=0.013),whereas the highdensity lipoprotein(Р=0.036)and 10-year ASCVD risk(Р=0.003)improved significantly only in women.Fifty-four patients(31%)achieved>5%weight loss.At the end of the study,the FLI decreased significantly in patients with(88.3±10.2 vs 71.4±19.6,P<0.001)and without>5%weight loss(83.5±10.3 vs 72.8±16.7,P<0.001).The changes in ALT,aspartate transaminase,glutamyltransferase,total cholesterol,and low-density lipoprotein levels were similar between the subgroups.CONCLUSION UDCA normalizes liver enzymes greatly within the first 3 mo of treatment,improves lipid profile and hepatic steatosis independent of weight loss,and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.

Giant androgen-producing adrenocortical carcinoma with atrial flutter: A case report and review of the literature

BACKGROUND Adrenocortical carcinoma(ACC),the second most aggressive malignant tumor,lacks epidemiological data worldwide;therefore,every new case can improve the understanding of the pathology and treatment of this malignancy.CASE SUMMARY We present the case of a 66-year-old Caucasian woman with a giant androgenproducing ACC(21 cm×17 cm×12 cm;2100 g),without metastases,which unusually presented with an acute onset of atrial flutter and congestive heart failure.The cardiac complications observed in our case support the hypothesis that androgen excess in women is a cardiovascular risk factor.Androgen excess in women can be a rare cause of reversible dilated cardiomyopathy,therefore a comprehensive approach to the patient is essential to improve the recognition of androgen-secreting ACC.The atrial flutter was remitted after initiation of drug treatment during admission.The severe heart failure was totally remitted at 6 mo after radical open surgery to remove the giant ACC.CONCLUSION Radical open surgery to remove a giant androgen-producing ACC was the firstline treatment to cure the excess of androgen,which determined the total remission of cardiac complications at 6 mo after surgery in the women of this case report.

稳定性慢性心力衰竭患者中NT-proBNP的长期临床变异

目的：评价稳定性慢性心力衰竭（CHF）患者中N-末端脑利钠肽前体（NT-proBNP）的长期临床变异。建议采用NT-proBNP来监测CHF患者尚需要NT-proBNP长期临床变异的精确资料。方法和结果：研究对象为在本心力衰竭诊疗中心接受治疗的患者，记录随访1年和2年时的用药情况、生化指标和NYHA分级。仅将从第1次随访至第2次随访后12个月这一时期用药和NYHA分级无变化，亦未入院或死亡的患者纳入分析。共78例患者符合标准，年变异率为30％（中位值；极差0％～111％）（百分比变化范围：-87％～397％）。

The Influence of Progesterone Gel Therapy in the Treatment of Fibrocystic Breast Disease

The effect of progesterone therapy on E2/P ratio changes during the luteal phase, and its consequences are on mastalgia and cyst, within a fibrocystic breast disease (FBD). Fifty women with FBD were included. Information for mastalgia and mastodynia were checked with a questionnaire. All women had (E2) and (P) concentration checked before and during the therapy on the 21st and 24th day of a cycle, ultrasound measured size and number of cysts before and during the therapy. T-test, X2-test, McNemar test, Wilcoxon test and Friedman test were used for statistics. There was a decrease E2/P relation during the therapy vs. before the treatment p < 0.01, as well as the decrease of E2 level on the 24th day during the therapy vs. same day of E2 level, before the therapy (p = 0.164). There was an increase of p level on the 24th day vs. on 24th day before the therapy (p < 0.001). During the therapy, it was found decrease in pain and tension (p < 0.001), and the number and size of the cysts (p < 0.001). Mastalgia and mastodynia significantly decreased during the local p gel therapy, and there was a significantly lower number and size of the cysts in patients with FBD.

Predictors of surgical complications in boys with hypospadias:data from an international registry

Background Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their occurrence.Methods Data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development(l-DSD)Registry.Logistic regressions,fisher's exact tests and spearman's correlation tests were performed on the data to assess associations between clinical factors and complication rates.Results Of the 551 eligible boys,data were available on 160(29%).Within the cohort,the median(range)External Masculinization Score(EMS)was 6(2,9).All presented with one or more additional genital malformation and 61(38%)presented with additional extragenital malformations.Disorders of androgen action,androgen synthesis and gonadal development were diagnosed in 28(18%),22(14%)and 9(6%)boys,respectively.The remaining 101(62%)patients were diagnosedas having non-specific 46,XY Disorders of Sex Development.Eighty(50%)boys had evidence of abnormal biochemistry,and gene variants were identified in 42(26%).Median age at first hypospadias surgery was 2 years(0,9),and median length of follow-up was 5 years(0,17).Postsurgical complications were noted in 102(64%)boys.There were no significant associations with postsurgical complications.Conclusions Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative complications.No clinical factors were significantly associated with complication rates.High complication rates with no observable cause suggest the involvement of other factors which need investigation.

Multi-targeted tyrosine kinase inhibitor sunitinib： a novel strategy for sporadic malignant pheochromocytoma

Sporadic malignant pheochromocytoma, a rare disease with poor prognosis, is always difficult to treat due in part to lack of effective agents. We presented three patients with advanced malignant pheochromocytoma treated by sunitinib, which indicates that sunitinib is an effective agent for this malignancy.

治疗胰高血糖素样肽-1类似物治疗2型糖尿病

什么是胰高糖素样肽-1类似物？ 胰高血糖素样肽-1（GLP-1）是一种天然生成的肽类激素，在进食后由肠道释放。GLP-1刺激胰岛素释放（肠促胰岛素效应），抑制胰高糖素释放（因而减少肝糖原异生），延迟胃排空以及增加饱腹感。天然GLP-1可因体内内肽酶如二肽基肽酶IV（DPP4）的作用而迅速降解，半衰期（tl／2）仅有几分钟。GLP-1类似物，同时也被称为肠促胰岛素类似物（艾塞那肽和利拉鲁肽），

非酒精性脂肪肝一例报道

将甲状腺功能减退视为非酒精性脂肪肝的致病因素。 非酒精性脂肪肝是常见慢性肝病，患病比例逐年上升（有报道为人群的30％～40％），是肝功能异常的常见原因。非酒精性脂肪肝可引起一系列组织学改变，包括单纯的肝细胞脂肪变性和肝细胞脂肪坏死，伴有不同程度的肝细胞纤维化，可促进肝病的进展和并发症（肝功能衰竭和肝脏肿瘤）的发生。

钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南

临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。