DPP4 inhibitors (DPP4i) are a class of newly developed antidiabetic drugs which preserve incretin hormones and promote postprandial insulin secretion. Although the cardiovascular effect of DPP4 inhibition has been substantially studied, the exact role of DPP4 in cardiovascular disease especially in humans remains elusive. Previous small studies and meta-analyses have suggested a benefit in both surrogate outcomes and cardiovascular events for these agents. However, there was growing evidence in recent years questioning the cardioprotective effect of DPP4i. Further, a signal of heart failure hospitalization in a recent large scale clinical trial SAVOR-TIMI 53 has called into question the safety of these agents and their utility in the treatment of cardiovascular disease. In this review, we will revisit the physiologic function of DPP4 and discuss its role in cardiometabolic disease based on recent experimental and clinical studies.
Introduction:Childhood malignancy, although a rare phenomenon, is still the leading cause of mortality in the pediatric population. Early diagnosis and treatment are imperative for the achievement of optimal prognosis. The study of factors facilitating the delay in diagnosis is thus of utmost importance, to both shorten the diagnostic delay and allow for early therapeutic intervention, facilitating a higher prognosis.Objective:To assess the referral pattern and the identification of potential delays in the diagnosis of childhood malignancy in a developing country.Methodology:The study was conducted in the Pediatric Hematology and Oncology department of Sri Ramachandra University, Chennai, India. The study included randomly selected 70 pediatric patients diagnosed with a hematological malignancy, from July 2012-August 2013. The parents were interviewed using a prepared questionnaire about patient symptomatology, interaction with healthcare providers, final diagnosis, and referral details. Data were statistically analyzed using Statistica® (STATsoft).Results:70 patients were included in the study (69% boys, 31% girls). The diagnostic delay was primarily due to the delay experienced in the healthcare system, with a mean delay of 26 days (Median: 18; Range: 5-39). Those from a lower socioeconomic background and whom opted for a non-allopathic treatment approach experienced higher diagnostic delays. Diagnostic time was significantly shorter for those who visited a pediatrician versus the patients who visited a general physician or super specialties (P = 0.043).Conclusions:Diagnostic delay is often associated with an extensive disease presentation, an aggressive therapeutic approach, and has a negative impact on patient prognosis. To lower mortality rate and facilitate a favourable prognosis, diagnosis requires a high degree of clinical suspicion and immediate intervention.
The identification of anaplastic lymphoma kinase (ALK) gene rearrangements in subsets of non-small cell lung cancer patients has provided with unparalleled opportunities to hinder the progression of this disease through targeting the activity of these specific molecules. Unfortunately most patients develop disease progression in less than a year of treatment with crizotinib, the first-generation ALK-inhibitor. Areas covered: We review the resistance mechanisms to ALK inhibitors as well as an overview of the clinical activity of the alectinib, a second generation ALK inhibitor. Expert commentary: Second generation ALK inhibitors as alectinib and ceritinib can overcome crizotinib-resistant mutations and improve central nervous system control. Novel third-generation inhibitors and combination of agents give hope of achieving an even longer disease control in the next decade.
e15124 Background: Metastatic ovarian involvement in primary gastrointestinal (GI) carcinomas (CA) is associated with a poor prognosis. We performed a survival analysis in patients with ovarian metastases, based on site of primary GI CA (appendiceal, colorectal (CRC), gastric, and pancreatic). We also examined the association between hyperthermic intraperitoneal chemotherapy (HIPEC) and death in these patients. Methods: A search was conducted in a single institution pathology database for patients with primary GI CA and ovarian metastases diagnosed from 2010 to 2017. The search yielded 39 patients, and data pertaining to tumor characteristics and treatment were obtained by chart review. Chi-square (log rank) test was used to test for associations between both site of primary GI CA and HIPEC, and death, and Kaplan-Meier analysis was done. P-value < 0.05 was deemed statistically significant. Results: CRC accounted for the majority of patients (51.29%) with appendiceal CA accounting for 23.08% and gastric and pancreatic cancer making up the remainder. Primary site of malignancy was associated with survival (p = 0.036), favoring those with appendiceal and colorectal primaries. A total of 30 patients (76.92%) received HIPEC. Having undergone HIPEC was significantly associated with survival (p = 0.017). Conclusions: Ovarian metastases secondary to gastric and pancreatic cancer were associated with inferior survival as compared to those with appendiceal or colorectal primaries. A significant association was demonstrated between HIPEC and survival. Further investigation to define the role of HIPEC in the treatment of carcinomas of gastrointestinal primaries is warranted.
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