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ABSTRACT BACKGROUND: Nowdays, more relevant applications of perinatal derivatives, such as amniotic membrane (AM), are emerging in our environment as a source of biomaterials for use in different healing processes. The study of anastomosis healing associated with antimetabolic drugs such as 5-fluorouracil (5-FU) is a potential target of AM. AIMS: To evaluate the healing effects of AM in rats treated with 5-FU at a dose of 20 mg/kg on the seventh day of postoperative evolution, regarding the parameters percentage of type I collagen (mature), cell viability, microvascular density and formation of granulation tissue. METHODS: Thirty-two Wistar rats were used, submitted to colotomy and colorraphy, separated into four groups of eight, which received different treatments daily, intraperitoneally, until the day of sacrifice: saline solution (C), 20 mg/kg 5-FU, 20 mg/kg 5-FU and AM. RESULTS: Treatment with 20 mg/kg of 5-FU, on the seventh postoperative day, induced adverse effects on the anastomotic healing process, evidenced by a decrease in the percentage of type I (mature) collagen, cell viability, microvascular density, fibrin-leukocyte scab formation and angiofibroblast proliferation; the use of AM under these conditions induced an improvement in the percentage of type I (mature) collagen. CONCLUSIONS: Treatment with 20 mg/kg of 5-FU on the seventh postoperative day induced adverse effects on the anastomotic healing process, and the use of AM under these conditions induced an improvement in the percentage of type I (mature) collagen.

Introduction: Tramadol/paracetamol combination is one of the most prescribed pain medications in Portugal. At the Regional Health Administration of Lisbon and Tagus Valley, 1 119 229 packages of tramadol/paracetamol were prescribed for 12 months, corresponding to the second most prescribed analgesic. We ask whether this drug is prescribed for acute and irruptive pain or if it is prescribed as a long-term treatment for chronic pain. Methods: This cross-sectional study describes the prescription of tramadol/paracetamol in a Portuguese primary care unit. The population studied corresponds to the 344 patients who received a tramadol/paracetamol prescription between July 2020 and June 2021. Results: In this period, a total of 687 prescriptions were made, corresponding to 2500 packages of tramadol/paracetamol, of which 1874 were bought. There was no statistically significant difference between the number of packages bought over the 4 trimesters (p = 0.275) and 35.3% of the patients bought this medication in more than one trimester. We found that 16.5% bought tramadol/paracetamol in an amount that allows a use of more than 90 days. Conclusion: This demonstrates that the tramadol/paracetamol combination plays a central role in the treatment of pain and that a significant percentage of patients use this medication chronically, questioning the adequacy of this therapy in these patients. However, larger studies that assess pain control are needed to support the results presented in this work.

Background There is still a lack of research on which diabetic drugs are more effective in preventing stroke. Our network metaanalysis aimed to compare cerebrovascular benefits among glucose-lowering treatments. Methods We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry for clinical trials from inception through May 25, 2021. We included both prespecified cerebrovascular outcomes and cerebrovascular events reported as severe adverse events. Subgroup analyses were conducted by stroke subtype, publication type, age of patients, baseline glycosylated hemoglobin (HbA1c), duration of type 2 diabetes mellitus, and cardiovascular risks. Results Of 2,861 reports and 1,779 trials screened, 79 randomized controlled trials comprising 206,387 patients fulfilled the inclusion criteria. In the pairwise meta-analysis, the use of glucagon-like peptide-1 (GLP-1) agonist was associated with a lower risk of total stroke compared with placebo (relative risk [RR], –0.17; 95% confidence interval [CI], –0.27 to –0.07). In the network meta-analysis, only the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitor was associated with a reduction of total stroke, compared with placebo (RR, 0.81; 95% CI, 0.67 to 0.98). In the subgroup analyses, the use of SGLT-2 inhibitor and GLP-1 agonist was associated with a lower risk of stroke in those with high HbA1c (≥8.0) and low-risk of cardiovascular disease, respectively. Conclusion SGLT-2 inhibitors and GLP-1 agonists were shown to be beneficial for stroke prevention in patients with type 2 diabetes mellitus.

Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial for preventing diabetes-related complications. Previous studies showed that monotherapy with a stepwise add-on approach was seldom effective for long-term durable glycemic control. Combination therapy, which refers to the use of two or more drugs to control hyperglycemia, has multiple benefits, including the ability to target a variety of pathophysiological processes underlying hyperglycemia. In clinical trials, initial combination therapy showed better glycemic control than monotherapy or a stepwise approach. Emerging evidence indicates that initial combination therapy is associated with preserved β-cell function and fewer complications in T2D. However, cost-effectiveness and adverse events with combination therapy are issues that should be considered. Therefore, initial combination therapy is an important option for patients with T2D that clinicians should consider with a view toward balancing benefits and potential harms. In this review, we summarize the literature addressing initial combination therapy in T2D, and we suggest optimal strategies based on clinical situations and patient characteristics.

Background To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM). Methods This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk

Background This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P

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Transcatheter arterial chemoembolization (TACE) is recommended by domestic and international guidelines for the treatment of patients with unresectable hepatocellular carcinoma (uHCC), and it is one of the most common treatment methods for patients with uHCC. The chemotherapy drugs commonly used in TACE for HCC include epirubicin, cisplatin, and fluorouracil, while it is still unclear which chemotherapy drug has a better clinical effect. This article summarizes the studies of different TACE regimens using different chemotherapy drugs in the treatment of patients with uHCC in the recent five years. TACE combined with sorafenib can significantly improve the survival of patients with advanced HCC and has been recommended for the treatment of such patients by Chinese Society of Clinical Oncology guidelines, and the efficacy of TACE combined with other tyrosine kinase inhibitors (TKI) has become a research hotspot. Studies have shown that compared with TACE combined with sorafenib in the treatment of patients with advanced HCC, TACE combined with lenvatinib can achieve a significantly longer progression-free survival time and a tendency of increase in median overall survival time. However, due to the variation of target receptors or downstream signals, resistance to molecular-targeted agents is still a challenging problem. TKI combined with immune checkpoint inhibitors may be a promising strategy for the treatment of patients with uHCC. Some studies suggest that triple therapy using TACE combined with TKIs and anti-PD-1/PD-L1 monoclonal antibody has better efficacy in improving the survival of patients with uHCC. This article reviews the studies of the efficacy and safety of TACE combined with targeted agents and TACE combined with anti-PD-1/PD-L1 monoclonal antibody in the treatment of patients with uHCC in the recent five years. [ABSTRACT FROM AUTHOR]

Objective To observe the efficacy and prognosis of edaravone dexborneol combined with intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in the treatment of ultra-early acute cerebral infarction (ACI). Methods A total of 163 patients with ultra-early ACI were randomly divided into the combination group (treated with edaravone dexborneol combined with intravenous thrombolysis with rt-PA, n=78) and the control group (treated with intravenous thrombolysis with rt-PA, n=85). Therapeutic effects and changes of superoxide dismutase (SOD), reactive oxygen species (ROS), malondialdehyde (MDA), neuron-specific enolase (NSE), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-12 (MMP-12), central nervous system-specific protein β (S100β), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), D-dimer (D-D), C-reactive protein (CRP), the National Institutes of Health Stroke Scale (NIHSS) scores, Modified Rankin Scale (mRS) scores and activity of daily living (ADL) scores were observed before and after treatment in the 2 groups. The fatality rate and the incidence of adverse reactions were compared between the two groups. Results After treatment, the total effective rate, SOD level and ADL score were higher in the combination group than those in the control group. Levels of ROS, MDA, NSE, MMP-9 and S100β, NIHSS score and mRS score were lower in the combination group than those in the control group (P＜ 0.05). There were no significant differences in fatality rate and incidence of adverse reactions between the two groups (P＞ 0.05). Conclusion Edaravone dexborneol combined with intravenous thrombolysis with rt-PA can improve the clinical effect in the treatment of patients with ultra-early ACI, and improve the prognosis. [ABSTRACT FROM AUTHOR]

Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ABSTRACT BACKGROUND: Surgical resection remains the main curative therapeutic modality for advanced gastric cancer. Recently, the association of preoperative chemotherapy has allowed the improvement of results without increasing surgical complications. AIMS: To evaluate the surgical and oncological outcomes of preoperative chemotherapy in a real-world setting. METHODS: A retrospective review of gastric cancer patients who underwent gastrectomy was performed. Patients were divided into two groups for analysis: upfront surgery and preoperative chemotherapy. The propensity score matching analysis, including 9 variables, was applied to adjust for potential confounding factors. RESULTS: Of the 536 patients included, 112 (20.9%) were referred for preoperative chemotherapy. Before the propensity score matching analysis, the groups were different in terms of age, hemoglobin level, node metastasis at clinical stage- status, and extent of gastrectomy. After the analysis, 112 patients were stratified for each group. Both were similar for all variables assigned in the score. Patients in the preoperative chemotherapy group had less advanced postoperative p staging (p=0.010), postoperative n staging (p

ABSTRACT BACKGROUND: Peritoneal carcinomatosis in gastric cancer is considered a fatal disease, without expectation of definitive cure. As systemic chemotherapy is not sufficient to contain the disease, a multimodal approach associating intraperitoneal chemotherapy with surgery may represent an alternative for these cases. AIMS: The aim of this study was to investigate the role of intraperitoneal chemotherapy in stage IV gastric cancer patients with peritoneal metastasis. METHODS: This study is a single institutional single-arm prospective clinical trial phase II (NCT05541146). Patients with the following inclusion criteria undergo implantation of a peritoneal catheter for intraperitoneal chemotherapy: Stage IV gastric adenocarcinoma; age 18–75 years; Peritoneal carcinomatosis with peritoneal cancer index

Abstract A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was the objective response rate per immune-related response criteria (irORR) at week 26 (a lower bound of the 90% confidence interval [CI] of > 10% was considered efficacious). The prespecified 43 patients (cervical, n = 18; endometrial, n = 25) were enrolled. The irORR was 11.1% (90% CI 2.0–31.0) in cervical cancer and 12.0% (90% CI 3.4–28.2) in endometrial cancer. Median duration of response was not reached in both cohorts. Median interval-censored progression-free survival was 4.1 weeks (95% CI 4.1–25.7) in cervical cancer and 3.6 weeks (95% CI 3.6–15.4) in endometrial cancer; median overall survival was 39.6 weeks (95% CI 15.0–67.0) and 37.4 weeks (95% CI 19.0–50.3), respectively. Grade ≥ 3 treatment-related adverse events were reported in 10 (55.6%) cervical cancer patients and 9 (36.0%) endometrial cancer patients. Health-related quality of life was generally stable over time. Responders had a significantly higher proportion of peripheral T cells when compared to nonresponders (p = 0.013). In conclusion, PRIMMO did not meet its primary objective in both cohorts; pembrolizumab, radiotherapy, and an IDC had modest but durable antitumor activity with acceptable but not negligible toxicity. Trial registration ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97).

BackgroundAdults with relapsed/refractory acute myeloid leukemia (AML) have poor prognosis, very low long-term survival rate and cure rate, and limited chemotherapy regimens.ObjectiveTo investigate the safety and efficacy of venetoclax (VEN) with HAAG 〔homoharringtonine (HHT) , Cytarabine (Ara-C) , aclacinomycin (Acla) , granulocyte stimulating factor (G-CSF) 〕 in relapsed/refractory AML.MethodsThe clinical data of 10 adult patients with relapsed/refractory AML treated in the First Affiliated Hospital of Bengbu Medical College were analyzed retrospectively, including: clinical characteristics (sex, age, diagnosis, chromosome, gene mutation, prognosis) , peripheral blood and bone marrow cytology, and the effect of Ven+Aza+HAAG regimen.ResultsAmong the 10 patients, there were 7 men and 3 women, with an average age of (47.9±11.3) years; 4 cases of M2 and 6 cases of M5 by FAB classification; 3 cases of good prognosis, 2 cases of fair and 5 cases of poor. The median levels of WBC count, hemoglobin content, and platelet count, as well as median percentage of bone marrow blast cells before chemotherapy of the patients were 4.10×109/L, 87.5 g/L, 66.00×109/L, and 63.5%, respectively, and after chemotherapy, the values of these four indicators were 3.28×109/L, 107.0 g/L, 78.00×109/L and 5.5%, respectively. Before VEN+Aza+HAAG regimen combined chemotherapy, the median number of chemotherapy used by the patients was 5. And after the combined therapy, there were 1 case of complete remission (CR) and 4 cases of CR with incomplete count recovery (CRi) , 3 cases of partial remission (PR) , and 2 cases of non-remission (NR) . The objective response rate of 10 patients was 80%, and median survival time was 〔6.5 (3.0, 8.5) 〕months. The toxic and side effects were mainly bone marrow suppression and infection. No patients died of treatment-related complications and other toxic and side effects.ConclusionCompared with traditional chemotherapy regimen, the use of Ven + Aza + HAAG with chemotherapy could significantly improve the objective response rate and remission degree, and prolong the survival in patients with relapsed/refractory AML, which is worthy of further study and has a prospect of clinical application.

ABSTRACT Objective To compare viral suppression in treatment-naïve adults starting antiretroviral therapy with dolutegravir (50mg)- and efavirenz (600mg)-based regimens. Methods We analyzed secondary data from Brazilian health information systems of people living with human immunodeficiency virus who started antiretroviral therapy between 2015 and 2017 in Minas Gerais, Brazil. The outcome was viral suppression, defined as the achievement of the first viral load

A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was the objective response rate per immune-related response criteria (irORR) at week 26 (a lower bound of the 90% confidence interval [CI] of > 10% was considered efficacious). The prespecified 43 patients (cervical, n = 18; endometrial, n = 25) were enrolled. The irORR was 11.1% (90% CI 2.0–31.0) in cervical cancer and 12.0% (90% CI 3.4–28.2) in endometrial cancer. Median duration of response was not reached in both cohorts. Median interval-censored progression-free survival was 4.1 weeks (95% CI 4.1–25.7) in cervical cancer and 3.6 weeks (95% CI 3.6–15.4) in endometrial cancer; median overall survival was 39.6 weeks (95% CI 15.0–67.0) and 37.4 weeks (95% CI 19.0–50.3), respectively. Grade ≥ 3 treatment-related adverse events were reported in 10 (55.6%) cervical cancer patients and 9 (36.0%) endometrial cancer patients. Health-related quality of life was generally stable over time. Responders had a significantly higher proportion of peripheral T cells when compared to nonresponders (p = 0.013). In conclusion, PRIMMO did not meet its primary objective in both cohorts; pembrolizumab, radiotherapy, and an IDC had modest but durable antitumor activity with acceptable but not negligible toxicity. Trial registration ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97). [ABSTRACT FROM AUTHOR]

Objective: To compare viral suppression in treatment-naïve adults starting antiretroviral therapy with dolutegravir (50mg)- and efavirenz (600mg)-based regimens. Methods: We analyzed secondary data from Brazilian health information systems of people living with human immunodeficiency virus who started antiretroviral therapy between 2015 and 2017 in Minas Gerais, Brazil. The outcome was viral suppression, defined as the achievement of the first viral load <50 copies/mL within 12 months after initiating antiretroviral therapy. This outcome was also compared with viral load <1,000 copies/mL and analyzed in two scenarios: intention-to-treat versus per-protocol. Time to viral suppression and adjusted odds ratio accompanied by 95% confidence intervals were estimated. Results: Of the 2,599 participants enrolled, 77.5% were men, and the median age was 34 years. In the intention-to-treat analysis, viral suppression was 58.1% for efavirenz and 76.7% for dolutegravir. People living with HIV on dolutegravir-based regimen were more likely to achieve viral suppression (aOR: 2.44; 95%CI: 2.01-2.95) and had a shorter median time to viral suppression (p<0.0001). Antiretroviral therapy initiation within <120 days, baseline CD4=T-cells =200 cells/mm3, and viral load <100,000 copies/mL had higher odds of viral suppression. According to the per-protocol analysis, viral suppression =90% was observed by considering viral load <1,000 copies/mL. Conclusion: Our study demonstrated that viral suppression improved after introducing dolutegravir, although the proportion of patients with viral load <50 copies/mL was lower than expected. Improved access to routine viral load examinations and continuous surveillance of the effectiveness of antiretroviral therapy should be considered. [ABSTRACT FROM AUTHOR]

Extraskeletal Ewing sarcoma in pregnancy is very rare in clinic, with a high rate of recurrence and metastasis, and there is no unified and effective treatment plan at present. This paper reports a case of pregnancy complicated with extraperitoneal Ewing sarcoma. Due to lumbosacral pain, a healthy full-term live female infant was successfully cesarean section in the First Hospital of Lanzhou University, who had previously received retroperitoneal tumor resection combined with left nephrectomy, supplemented with postoperative chemotherapy, combined with relevant medical history and examination to consider the recurrence and metastasis of extraperitoneal Ewing sarcoma. Because extraosseous Ewing sarcoma in pregnancy is very rare, the treatment is more difficult and the prognosis is poor. It is suggested that the suspected pregnant women should be followed up on the basis of regular prenatal examination in clinical work to find the focus in time. Once diagnosed, treatment strategies should be developed under the multi-disciplinary joint management mode to help patients overcome the challenges posed by pregnancy associated cancer and minimize adverse outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Cenobamate is an antiseizure medication (ASM) approved in Europe as adjunctive therapy for adults with inadequately controlled focal seizures. This post hoc analysis reports onset of efficacy and characterizes time to onset, duration, and severity of the most common treatment‐emergent adverse events (TEAEs) during cenobamate titration. Materials & Methods: Adult patients with uncontrolled focal seizures taking 1 to 3 concomitant ASMs were randomized to receive adjunctive cenobamate or placebo (double‐blind studies C013 and C017) or cenobamate (open‐label study C021). Outcome assessments included efficacy (median percentage change in seizure frequency and onset [studies C013 and C017]) and safety (onset, duration, and severity of TEAEs [all studies]). Results: Onset of efficacy was observed by Weeks 1 to 4 of titration in studies C013 and C017 which used a faster titration schedule than study CO21. In study C013, the median percentage seizure frequency reduction was 36.7% in patients receiving cenobamate versus 16.3% in those taking placebo (p =.002); in study C017, significant differences in seizure frequency emerged in Week 1 and continued throughout titration between all cenobamate groups and placebo (p <.001). The most commonly reported TEAEs were somnolence, dizziness, fatigue, and headache, with first onset of each reported as early as Week 1; however, the majority resolved. Conclusions: Reductions in seizure frequency occurred during titration with initial efficacy observed prior to reaching the target dose. These reductions were regarded as clinically meaningful because they may indicate early efficacy at lower doses than previously expected and had a considerable impact on patient quality of life. Long‐term treatment with adjunctive cenobamate was generally safe and well‐tolerated. [ABSTRACT FROM AUTHOR]

We assessed the glycaemic durability with early combination (EC; vildagliptin+metformin [MET], n=22) versus MET monotherapy (n=17), among newly-diagnosed type 2 diabetes mellitus (T2DM) enrolled (between 2012 and 2014) in the VERIFY study from Korea (n=39). Primary endpoint was time to initial treatment failure (TF) (glycosylated hemoglobin [HbA1c] ≥7.0% at two consecutive scheduled visits after randomization [end of period 1]). Time to second TF was assessed when both groups were receiving and failing on the combination (end of period 2). With EC the risk of initial TF significantly reduced by 78% compared to MET (n=3 [15%] vs. n=10 [58.7%], P=0.0228). No secondary TF occurred in EC group versus five patients (29.4%) in MET. Patients receiving EC treatment achieved consistently lower HbA1c levels. Both treatment approaches were well tolerated with no hypoglycaemic events. In Korean patients with newly diagnosed T2DM, EC treatment significantly and consistently improved the long-term glycaemic durability as compared with MET.

Background Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P

Biliary malignant tumors have an insidious onset and rapid development, and most patients have lost the opportunity for radical surgery at initial diagnosis and often have poor prognosis. Gemcitabine-based chemotherapy is the first-line treatment for biliary malignant tumors, but with a limited clinical effect. The improvement in next-generation sequencing technology provides the possibility for the precise treatment of biliary malignant tumors, but the application and development of the precise treatment of biliary malignant tumors are limited by the low positive rate of targets and the poor accessibility of therapeutic drugs. The advent of the era of immunotherapy represented by the immune checkpoint inhibitor PD1/PD-L1 monoclonal antibody brings a promising future for the treatment of malignant tumors, including biliary malignant tumors. Combined chemotherapy and/or targeted therapy based on immune checkpoint inhibitors has shown a good effect in the treatment of biliary malignant tumors, which is the direction of the treatment of advanced biliary malignant tumors in the future. [ABSTRACT FROM AUTHOR]

The worldwide prevalence of non-alcoholic fatty liver disease is around 25%, and that of nonalcoholic steatohepatitis (NASH) ranges from 1.5% to 6.45%. Patients with NASH, especially those with fibrosis, are at higher risk for adverse outcomes such as cirrhosis and liver-related mortality. Although vitamin E, pioglitazone, and liraglutide improved liver histology in randomized trials, there are currently no Food and Drug Administration-approved drugs for NASH. Five pharmacologic agents—obeticholic acid, elafibranor, cenicriviroc, resmetirom, and aramchol—are being evaluated in large, histology-based phase 3 trials. Within 2 to 4 years, new and effective drugs for the treatment of NASH are expected. Additionally, many phase 2 trials are ongoing for various agents. Based on the results of phase 2 and 3 trials, combination treatments are also being investigated. Future treatment strategies will comprise drug combinations and precision medicine based on the different phenotypes of NASH and treatment response of the individual patient.

In recent years, the recurrence rate and mortality rate of endometrial cancer are on the rise, seriously threatening women′ s life and health. Endocrine therapy plays a very important role in adjuvant therapy for postoperative prevention of recurrence and metastasis of endometrial cancer, as well as in the treatment of advanced or recurrent metastatic endometrial cancer. Aromatase inhibitors are common adjuvant endocrine heraputic drugs in clinical practice. They are highly selective and can reduce the stimulation of endometrial cancer cells by inhibiting estrogen synthesis, to inhibit the proliferation of tumor cells. This article reviews the clinical efficacy of aromatase inhibitors in endometrial cancer and discusses potential strategies to enhance the efficacy of aromatase inhibitors, such as combination of paclitaxel and carboplatin, combination of novel targeted therapies, and metformin. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to explore the vision of a large multidisciplinary group of physicians treating type 2 diabetes mellitus (T2DM) in Spain, with a special focus on controversial management aspects. The perceptions of primary care (PC) physicians and hospital care (HC) specialists were compared. Methods: This was a mixed survey that included Delphi-like statements and opinion, attitude and behaviour (OAB) questions. The Delphi-like statements were assessed on the basis of the degree of agreement among respondents, and a descriptive analysis was performed on the answers to the OAB questions. Results: A total of 296 participants responded to the first wave of the survey, of whom 293 responded to the second wave (211 from PC and 80 from HC, with two respondents for whom there were no data on specialty). A high degree of consensus (CNS ≥ 0.8) was obtained in all the statements. A proactive approach to detect prediabetes or T2DM in asymptomatic people was highly supported (80.4% of agreement). Introducing early treatment intensification was considered to favour the durability of glycaemic control and to delay the progression of the disease (80.4%). There was agreement on the statement that glycaemic variability constitutes a risk factor for chronic complications, although differences in the perceptions of HC physicians and PC specialists were identified (86.3 vs. 80.1%, respectively). More HC physicans than PC specialists considered comorbidities to affect the ability to self-care (95 vs. 82.9%, respectively). Conclusions: The survey revealed that there was a high, albeit not universal, degree of agreement amongst PC physicians and HC specialists in relation to prevention, screening and diagnosis of T2DM; early treatment intensification; dysglycaemias; and the management of patients with comorbidities. The statement on the management of patients with comorbidities elicited the highest difference between PC physicans and HC specialists. The results of this survey indicate that there is room for improvement in terms of implementing strategies in these areas. [ABSTRACT FROM AUTHOR]

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Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• Anti-CTLA-4 antibody quavonlimab + pembrolizumab was assessed in extensive-stage SCLC. • Encouraging antitumor activity was observed in patients with extensive-stage SCLC. • The combination was tolerable with manageable toxicities. This first-in-human phase I study (NCT03179436) investigated anti–cytotoxic T-lymphocyte-associated protein 4 monoclonal antibody quavonlimab and anti–programmed death 1 monoclonal antibody pembrolizumab in patients with advanced solid tumors. The study was conducted in two parts: dose-escalation (part 1) and dose-confirmation (part 2). First-line treatment with quavonlimab + pembrolizumab conferred encouraging antitumor activity (objective response rate [ORR], 28%-40%) and was generally well tolerated (grade ≥ 3 treatment-related adverse events [TRAEs] were lowest with quavonlimab 25 mg every 6 weeks [Q6W] at 30% and highest with quavonlimab 75 mg Q3W at 57%) in non–small cell lung cancer. We present data from patients with extensive-stage small cell lung cancer (SCLC) receiving second-line or later therapy. Patients with stage III/IV SCLC received quavonlimab 75 mg Q6W plus pembrolizumab 200 mg Q3W for ≤ 2 years. Primary endpoints were safety and tolerability; ORRs as assessed by blinded independent central review per Response Evaluation Criteria In Solid Tumors v1.1 was a secondary endpoint. Progression-free survival (PFS), overall survival (OS), and the correlation of response with PD-L1 expression were exploratory endpoints. Forty patients with extensive-stage SCLC received treatment; median follow-up was 13 months. Dose-limiting toxicity occurred in 4 patients (10%). TRAEs occurred in 80% of patients; grade 3 events occurred in 33% of patients and no grade 4/5 events were reported. Confirmed ORRs (95% CI) were 18% (7–33) among all patients, 7% (<1–34) for PD-L1–positive tumors (n = 14), and 19% (5–42) for PD-L1–negative tumors (n = 21). Response duration ranged from 2.9 to 19.1+ months. Median PFS was 2.0 months; 6-month PFS rate was 26%. Median OS was 11.0 months; 6-month OS rate was 66%. Encouraging antitumor activity was observed with quavonlimab + pembrolizumab in patients with extensive-stage SCLC; responses were observed in PD-L1–positive and PD-L1–negative tumors. The combination was tolerable with manageable toxicities. [ABSTRACT FROM AUTHOR]

BackgroundThere is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM.MethodsThis multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement.ResultsGlycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: −0.81%, P

Patients with lepromatous leprosy that have received treatment for many years usually get follow up biopsies for persistent skin lesions or positive bacilloscopy even if the values are lower than in the initial bacilloscopy. We report the case of a 48-year old woman with long-standing lepromatous leprosy of 15 years of evolution, with a bacterial index of 4 in the direct smear and the initial skin biopsy. The patient was treated with multidrug therapy for 32 months although the treatment recommended by the World Health Organization (WHO) is only for 12 months. A skin biopsy was taken to determine if there was an active disease. We observed a diffuse dermal inflammation with numerous foreign body giant cells and vacuolated macrophages (Virchow´s cells). These cells contained granular acid-fast material that was also positive with immunohistochemistry for BCG. There were fragmented bacilli and the BI was 2. These cells were also strongly positive for CD68. The biopsy was interpreted as a residual form of lepromatous leprosy that did not require further multidrug therapy. We have observed similar histological profiles in several cases. The lack of clinical data makes it a histological challenge. The accumulation of lipids in these giant cells is due to bacillary destruction and fusion of vacuolated macrophages. We discuss here the role of bacillary and host lipids in the pathogenesis of lepromatous leprosy. We concluded that there was no need to extend the 12-month multidrug therapy recommended by WHO.

BackgroundWe evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin.MethodsA total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24.ResultsThe add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P

Copyright of Der Pneumologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background/Aim. The era of direct-acting antiviral (DAA) regimen in the treatment of chronic hepatitis C virus (HCV) started in 2011. The aim of this study was to assess the antiviral efficacy and safety of DAA regimen, ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) + dasabuvir (DSV) + ribavirin (RBV), in patients with chronic HCV infection, genotype 1. Methods. The real-life data were collected. The study was multicentric and included seven infectious diseases and hepatology departments in Serbia. A total of 21 patients were enrolled in the OBV/PTV/r + DSV + RBV early access program, 20 of which were previously treated with pegylated interferon + RBV, while 1 was treatment-naive. All patients received the adequate doses of these antiviral drugs. RBV was not given to the patients with HCV genotype 1b infection according to the therapeutic protocol. For the majority of patient, the treatment duration lasted for 12 weeks. For the patients with liver cirrhosis, who were infected with HCV genotype 1a, the duration of treatment was 24 weeks. Viremia was assessed at four points in time: at baseline, 4 weeks after the treatment beginning (rapid viral response, RVR), 12 or 24 weeks after the treatment beginning (end of treatment response – ETR) and 12 weeks after the end of treatment (sustained viral response – SVR). SVR, as a confirmation of the absence of HCV was considered as endpoint of successful treatment. Results. Complete RVR, ETR and SVR were achieved in 64.71%, 85.71% and 95.24% of the patients, respectively. Only 3 patients had mild adverse effects which did not required dose reduction. Conclusion. The treatment of the patients with a chronic HCV infection with OBV/PTV/r + DSV + RBV resulted in excellent antiviral activity and tolerability.

Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Studies have shown that rates of lithium use for bipolar disorder in the United States declined through the 1990s as other mood stabilizing anticonvulsants and second-generation antipsychotics (SGAs) became more popular. We examined trends of medications for bipolar disorder from 1996 to 2015.Methods: Twenty years of data from the National Ambulatory Medical Care Survey (NAMCS) were used. Weighted percentages of reported use of lithium, anticonvulsants, SGAs and antidepressants were calculated over two-year intervals. Logistic regression was used to examine factors related to polytherapy.Results: Reported use of lithium declined from 38.1% (95%CI: 29.8% - 46.3%) in 1996-97 to 14.3% (95%CI: 10.6% - 18.1%) in 2006-07 and has remained stable since. During this time, reports of SGAs more than doubled. SGAs and/or anticonvulsants were reported in 75.4% (95%CI: 69.5% - 81.3%) of visits with bipolar diagnoses in 2014-15. Polytherapy increased by approximately 3% every two years and in 2014-15 occurred in over 30% of visits. Antidepressants were reported in 40-50% of visits, but their reported use without other mood stabilizers decreased from 18.2% (95%CI: 11.7% - 24.8%) in 1998-99 to 7.5% (95%CI: 4.2% - 10.9%) in 2014-15.Limitations: The sample had limited power to study the effect of individual medications or the potential for differing effects in certain sub-groups of patients.Conclusions: This study further documents the declining use of lithium for bipolar disorder, and corresponding increase in use of anticonvulsants and SGAs, despite the fact that lithium is typically recommended as a first line therapy for bipolar disorder. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Clinical Healthcare is the property of Chinese Journal of Clinical Healthcare and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Helicobacter pylori eradication has become increasingly difficult as resistances to several antibiotics develop. We aimed to compare Helicobacter pylori eradication rates between triple therapy and sequential therapy in a naive Portuguese population. Material and Methods: Prospective randomized trial including consecutive patients referred for first-line Helicobacter pylori eradication treatment. Exclusion criteria: previous gastric surgery/neoplasia, pregnancy/lactancy, allergy to any of the drugs. The compared eradication regimens were triple therapy (pantoprazol, amoxicillin and clarithromycin 12/12 hours, 14 days) and sequential therapy (pantoprazol 12/12 hours for 10 days, amoxicillin 12/12 hours for days 1 - 5 and clarithromycin plus metronidazol 12/12 hours during days 6 - 10). Eradication success was confirmed with urea breath test. Statistical analysis was performed with SPSS v21.0 and a p-value < 0.05 was considered statistically significant. Results: Included 60 patients, 39 (65%) female with mean age 52 years (SD ± 14.3). Treatment groups were homogeneous for gender, age, indication for treatment and smoking status. No statistical differences were encountered between sequential and triple therapy eradication rates (86.2% vs 77.4%, p = 0.379), global eradication rate was 82%. Tobacco consumption was associated with a significantly lower eradication success (54.5 vs 87.8%, p = 0.022). Discussion: In this randomized controlled trial in a naive Portuguese population, we found a satisfactory global Helicobacter pylori eradication rate of 82%, with no statistical differences observed in the efficacy of the treatment between triple and sequential regimens. Conclusion: These results support the use of either therapy for the first-line eradication of Helicobacter pylori.