Introduction: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease (CVD). These observations suggest that pharmacological strategies, which reduce inflammation, may be therapeutically useful in treating obesity, type 2 diabetes and associated CVD.
Area covered: The article covers novel strategies, using either small molecules or monoclonal antibodies. These strategies include: approaches targeting IKK-b-NF-kB (salicylates, salsalate), TNF-α (etanercept, infliximab, adalimumab), IL-1β (anakinra, canakinumab) and IL-6 (tocilizumab), AMP-activated protein kinase activators, sirtuin-1 activators, mammalian target of rapamycin inhibitors and C-C motif chemokine receptor 2 antagonists.
Expert opinion: The available data supports the concept that targeting inflammation improves insulin sensitivity and β-cell function; it also ameliorates glucose control in insulin-resistant patients with inflammatory rheumatoid diseases as well in patients with metabolic syndrome or T2DM. Although promising, the observed metabolic effects remain rather modest in most clinical trials. The potential use of combined anti-inflammatory agents targeting both insulin resistance and insulin secretion appears appealing but remains unexplored. Large-scale prospective clinical trials are underway to investigate the safety and efficacy of different anti-inflammatory drugs. Further evidence is needed to support the concept that targeting inflammation pathways may represent a valuable option to tackle the cardiometabolic complications of obesity. 相似文献
Objective: The clinical course > 6 months after the initiation of linagliptin in patients with type 2 diabetes was compared among the groups divided by their renal function.Methods: Two hundred and sixteen Japanese patients with type 2 diabetes treated with 5 mg once daily linagliptin were studied as the treated set. One hundred and forty-five subjects whose medications were not changed during the observation period were investigated as the full analysis set to assess the effectiveness. The subjects were divided into three groups based on an eGFR: eGFR ≥ 60, 59 – 45 and < 45 ml/min/1.73 m2. The parameters were analyzed separately in the patients receiving monotherapy and additional therapy of linagliptin.Results: The HbA1c (NGSP) levels significantly improved in both the patients receiving monotherapy and additional therapy. The changes in the HbA1c levels at 6 months were not significantly different between the groups with an eGFR ≥ 60, 59 – 45 and < 45 ml/min/1.73 m2 receiving monotherapy (?1.0, ?0.8 and ?0.8%, respectively). Similarly, those were not significantly different between the different groups receiving additional therapy (?0.6, ?0.5 and ?0.7%, respectively).Conclusions: Linagliptin is considered to be effective for patients with type 2 diabetes and renal impairment in the present analysis performed at our institution. 相似文献
Malignant neoplasms are the leading cause of death in Korea. We aimed to examine if metformin use in cancer survivors reduces all-cause mortality. This study was retrospectively designed based on data from the Korean National Health Insurance Service-National Health Screening Cohort (HEALS) between 2002 and 2015. The Kaplan–Meier estimator and log-rank test was performed to estimate the survival function according to metformin usage (3721 metformin non-users with diabetes, 5580 metformin users with diabetes, and 24,483 non-diabetic individuals). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated using Cox proportional hazards regression models.The median follow-up duration was 4.2 years. The HRs (95% CIs) for all-cause mortality of metformin users and the non-diabetic group were 0.762 (0.683–0.850) and 1.055 (0.966–1.152) in men and 0.805 (0.649–0.999), and 1.049 (0.873–1.260) in women, respectively, compared with metformin non-users among diabetic cancer survivors, in a fully adjusted model. After stratifying metformin users into pre- and post-diagnosis of cancers, adjusted HRs (95% CIs) of pre- and post-diagnosis metformin users for all-cause mortality were 0.948 (0.839–1.071) and 0.530 (0.452–0.621) in men and 1.163 (0.921–1.469) and 0.439 (0.323–0.596) in women, respectively.Metformin use in cancer survivors with diabetes reduced overall mortality rates. In particular, metformin use after cancer diagnosis, not before cancer diagnosis, was inversely associated with overall mortality.Active treatment with metformin for diabetic cancer survivors after cancer diagnosis can improve their survival rates. 相似文献
Background:It is unclear whether there are false positive or negative results in the effects of sodium-glucose transporter 2 (SGLT2) inhibitors on various cardiovascular and renal outcomes in patients with type 2 diabetes. We aimed to explore this issue by a meta-analysis with trial sequential analysis.Methods:We included randomized trials evaluating the effects of SGLT2 inhibitors on cardiorenal endpoints in type 2 diabetic patients. Eight endpoints evaluated in the study were fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, major adverse cardiovascular events (MACE), cardiovascular death or hospitalization for heart failure (CVD or HHF), all-cause death (ACD), cardiovascular death (CVD), hospitalization for heart failure (HHF), and kidney function progression (KFP). Meta-analysis and trial sequential analysis was conducted for each endpoint.Results:Seven randomized trials of SGLT2 inhibitors were included for pooled analysis. Compared with placebo, SGLT2 inhibitors significantly reduced the risk of MACE (HR 0.89, 95% confidence interval [CI] 0.84–0.94), MI (HR 0.91, 95% CI 0.84–0.99), CVD (HR 0.86, 95% CI 0.79–0.93), CVD or HHF (HR 0.77, 95% CI 0.73–0.82), HHF (HR 0.67, 95% CI 0.62–0.74), KFP (HR 0.63, 95% CI 0.56–0.70), and ACD (HR 0.88, 95% CI 0.83–0.94), whereas SGLT2 inhibitors did not have significant effects on stroke (HR 0.98, 95% CI 0.88–1.09). Trial sequential analyses for MI and stroke showed that cumulative Z curve did not cross trial sequential monitoring boundary and required information size, whereas those for the other 6 endpoints showed that cumulative Z curve crossed trial sequential monitoring boundary and/or required information size.Conclusions:Compared with placebo, SGLT2 inhibitors conclusively reduce the risk of MACE, CVD or HHF, ACD, CVD, HHF, and KFP in patients with type 2 diabetes, whereas the effects of SGLT2 inhibitors on MI and stroke are not conclusive and need to be further assessed in future studies with the adequate sample size to reject or accept the effect size. 相似文献
Introduction: Central nervous system infection continues to be an important cause of mortality and morbidity worldwide. Our incomplete knowledge on the pathogenesis of how meningitis-causing pathogens cause CNS infection and emergence of antimicrobial resistance has contributed to the mortality and morbidity. An early empiric antibiotic treatment is critical for the management of patients with bacterial meningitis, but early recognition of bacterial meningitis continues to be a challenge.
Areas covered: This review gives an overview on current therapeutic strategies for CNS infection with a focus on recent literature since 2010 on bacterial meningitis. Bacterial meningitis is a medical emergency, requiring early recognition and treatment. The selection of appropriate empiric antimicrobial regimen, after incorporating the epidemiology of bacterial meningitis, impact of vaccination, emergence of antimicrobial-resistant bacteria, role of adjunctive therapy and the current knowledge on the pathogenesis of meningitis and associated neuronal injury are covered.
Expert opinion: Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood–brain barrier, with efficacy in cerebrospinal fluid. Emergence of CNS-infecting pathogens with resistance to conventional antibiotics has been increasingly recognized, but development of new antibiotics has been limited. More complete understanding of the microbial and host factors that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis. 相似文献
Rationale:The diagnosis of type IV branchial cleft cyst (BCC) according to the Bailey classification is very challenging due to lack of specific clinical manifestations in the early stage of the disease. Here, we present the transoral surgical route of endoscopic resection of second BCC in the parapharyngeal space (PPS) with good outcomes.Patient concerns:A 21-year-old man with a 1-year history of snoring complained about sore throat for 1 month and a fever that lasted for 3 days.Diagnoses:On admission, physical examination revealed a temperature of 39°C, pain when swallowing accompanied with a lump sensation in the throat, and inability to open mouth more than 3 cm. Blood testing revealed 19.29 × 109 white blood cells (WBCs)/L and 14.94 × 109 neutrophils/L. A cervical computed tomography (CT) examination revealed a mass with liquid density of 6.2 × 4.0 × 7.7 cm3 in the left parapharyngeal space (PPS) and pharyngeal cavity stenosis. Postoperative pathology showed the existence of lymphoepithelial cysts (left PPS), which was in accordance with the diagnosis of BCC.Interventions:The patient was administered 1.5 g ceftazidime every 12 hours, anti-inflammatory drugs, and incision drainage was performed subsequently. Then, endoscopy-assisted resection of the left PPS was performed via the transoral route. We used low-temperature plasma and an 8-Fr Foley catheter with a water capsule during the surgery.Outcomes:After resection of the mass, the patient''s blood results returned to within the normal range and his symptoms improved. Five days postoperatively, the incision made in the palatine arch of the pharynx opened up by 1 cm, and eventually the wound and laceration healed. Normal oral eating was restored, and no complications were observed.Lessons:Magnetic resonance imaging (MRI), and color Doppler ultrasound can be useful to diagnose BCC in PPS, which rarely occurs in the clinical setting. Extended endoscopy provides a satisfactory surgical field for trans-oral resection allowing complete resection of the BCC without serious postoperative complications. 相似文献
Background:Recently, many clinical experiments have evaluated the influences of liraglutide in the treatment of type 2 diabetes. However, the outcomes of these studies are inconsistent, and the number of high-quality prospective trials that conducted to assess the cardiovascular safety is limited. Hence, for this research, it was implemented for the assessment of the cardiovascular effectiveness and safety of liraglutide in type 2 diabetes patients.Methods:This research was a 26-week active controlled and randomized trial. Our research protocol follows the guidelines of Good Clinical Practice issued via the Helsinki Declaration and International Conference on Coordination. All the patients will receive the written informed consent in order to involve in our clinical experiment. The participants with type 2 diabetes aged from 18 years to 80 years, patients with 45.0 kg/m2 body-mass index or less, and with glycosylated hemoglobin of 7.5 to 10.0 percent, and received metformin (daily 1500 mg or more) for 3 months or longer were eligible. All the patients were randomized to 1 of 2 interventions (in the ratio of 1:1): liraglutide placebo once daily (blinded) and liraglutide once daily (blinded), respectively, both combined with the glimepiride and metformin (open-labeled). For the efficacy variable, the major endpoint was the baseline glycated hemoglobin change after treating for 26 weeks. The secondary end points involved: the percentage of participants who achieved the goals of postprandial blood glucose, fasting blood glucose, and glycosylated hemoglobin; the changes of mean postprandial blood glucose, fasting blood glucose, and the body weight, pancreatic B-cell function index, and changes in blood pressure and insulin resistance assessed by homeostasis model.Conclusions:For this research, the limitations involve the short trial period and the limitation of glimepiride in some countries, thus excluding the maximum doses of glimepiride.Trial registration:This study protocol was registered in Research Registry (researchregistry6306). 相似文献