Glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors as add-on therapy for patients with type 2 diabetes? A systematic review and meta-analysis of surrogate metabolic endpoints.

OBJECTIVE: As sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are second-line treatment options in type 2 diabetes mellitus (T2DM), our study sought to provide precise effect estimates regarding the role of GLP-1RAs vs SGLT-2is as add-on treatments in patients uncontrolled by metformin monotherapy. RESEARCH DESIGN AND METHODS: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and 'grey literature' were searched from their inception up to December 2019 for randomized controlled trials (RCTs) with durations≥12weeks to evaluate the safety and efficacy of adding a GLP-1RA vs an SGLT-2i in patients with T2DM. RESULTS: Three eligible RCTs were identified. Administration of GLP-1RAs vs SGLT-2is resulted in significant decreases in HbA1c with no significant impact on either body weight or fasting plasma glucose. GLP-1RA treatment led to a significant increase in odds for achieving an HbA1c<7% compared with SGLT-2is, whereas no difference was detected in body weight reductions of>5%. Significantly greater risk for any hypoglycaemia, nausea and diarrhoea, and lower risk for genital infections, was also observed with GLP-1RAs, while no differences regarding severe hypoglycaemia, treatment discontinuation and impact on blood pressure levels were identified. No other major safety issues arose. CONCLUSION: Our meta-analysis suggests that GLP-1RAs provide better glycaemic effects than SGLT-2is in patients with T2DM uncontrolled by metformin, albeit while increasing risk for hypoglycaemia and gastrointestinal adverse events.

Atypical teratoid/rhabdoid tumor of the central nervous system in an 18-year-old patient.

OBJECTIVE: Atypical teratoid/rhabdoid tumors are aggressive neoplasms of the central nervous system occurring mainly in the early childhood and rarely in adults. We described a case of this tumor in an 18-year-old male patient without previous medical history. MATERIAL AND METHODS: The neoplasm was localized in the right frontotemporal area of the brain and was totally excised. The specimen was fixed in formalin and embedded in paraffin. The histological and immunohistochemical features of the neoplasm were assessed, while sequencing analysis as well as interphase fluorescence in situ hybridization (FISH) were performed. RESULTS: Histological and immunohistochemical analysis demonstrated atypical rhabdoid cells strongly and diffusely positive for EMA and Vimentin as well as focally immunoreactive for SMA and GFAP. Additionally, though no abnormalities detected in the coding sequence of the INI1 gene, interphase FISH studies were consistent with a homozygous deletion of the INI1 gene in the majority of examined nuclei. INI1 immunostaining demonstrated diffuse loss of nuclear INI1 expression in tumor cells. Taken together, the results were consistent with a diagnosis of atypical teratoid/rhabdoid tumor (ATRT). CONCLUSIONS: 26 previous cases of ATRT have been reported in adults, thus far. To our knowledge, this is the eighth case of an ATRT reported in an adult patient having genetic confirmation and the first one in which the tumor is, partly, localized in the right temporal area of the brain. This unusual presentation underlines the necessity of considering this devastating neoplasm in the differential diagnosis of malignant brain tumors of young adults.

Preclinical studies of steroid-linked nitrosoureas in murine pancreatic adenocarcinoma PANO2.

PURPOSE: In earlier studies, this laboratory carried out research on the synthesis and anticancer evaluation of hybrid compounds, which combine two molecules in one such as homo-aza-steroidal esters (HASE) of carboxylic derivatives of N, N-bis (2-chloroethyl) aniline. In this combination, steroidal hormones are employed as carriers for transporting the alkylating agents to specific targeted tissues. Aiming to continue our research, we used alkylating agents, as nitrosoureas, instead of nitrogen mustards. In this work the N-[N- (2-chloroethyl)-N-nitroso-carbomoyl]-L-alanine (CNC-ala) has been used and was bound to 7 newly synthesized modified steroidal esters (carrier molecule) of nitrosourea and the hybrid molecules were tested for antitumor activity against PANO2 murine pancreatic adenocarcinoma. MATERIALS AND METHODS: PANO2 adenocarcinoma was used in this study. C57Bl mice were used for chemotherapy evaluation. The activity was assessed from the inhibition of tumor growth and the oncostatic parameter T/C %. RESULTS: The antitumor activity displayed by 7 hybrid steroidal esters of nitrosourea was quite interesting. It was able to discern 4 of 7 compounds that exhibited considerable antitumor activity, increasing the lifespan of the tumor-bearing mice by inhibiting the tumor growth. CONCLUSION: The comparative study of 7 newly synthesized hybrid steroidal esters of nitrosourea shows that the antitumor effects of compound 7, which has an enlarged (7 carbon atoms) A-lactamic ring and nitrosourea esterified at the position 17, which seems to be the most appropriate for the connection of a DNA cross-linking amino acid derivative is superior.

Metastatic parathyroid carcinoma (mPCa): natural history and treatment of a case.

We report the case of a 46-year-old male patient who, after disease-free intervals of five, four and one and a half years following resection of an 'atypical' parathyroid adenoma in 1982, relapsed with clinical and laboratory recurrence of primary hyperparathyroidism (PHP). Noninvasive, traditional and modern imaging methods localized small distinct metastatic foci in both lungs without evidence of primary thyroid, neck or mediastinal tumor. Three successive bilateral lung nodule excisions resulted in a long PHP remission, while a three month treatment with normal saline infusions, diuretics, calcitonine and pamidronate infusions, following the last recurrence, resulted in moderate improvement of hypercalcemia and hypercalciuria with no effect on both PTH secretion or on the size of new metastatic lung foci. Recurrent mPCa with or without secretion of biologically active PTH is optimally treatable with successive surgical resections of the metastases and intermittent medical treatment to achieve PTH secreting tumor mass reduction and a beneficial metabolic effect.

Detection of methylation in the CpG islands of the p16INK4A, RASSF 1A and methylguanine methyltransferase gene promoters in pancreatic adenocarcinoma.

Pancreatic cancer consists of an accumulation of genetic and epigenetic alterations. Recently, aberrant methylation of CpG islands of cancer-related genes has emerged as an important epigenetic mechanism of their transcriptional dysregulation during tumour development [1]. Therefore, new diagnostic methods, for early detection based on a better understanding of the molecular biology of pancreatic cancer, are required. We examined the methylation status of p(16INK4A), RASSF 1A and methylguanine methyltransferase (MGMT) genes considered to be inactivated by promoter methylation in several tumours.The p(16INK4A) is an important G1/S cell cycle regulator gene [2]. RASSF 1A gene is involved in apoptotic signalling, microtubule stabilization and cell cycle progression [3]. The MGMT gene removes mutagenic and cytotoxic alkyl-adducts from the O6-position of guanine in DNA. Hypermethylation of the gene leads to the inactivation of DNA repair and to microsatellite instability [4].To date, little is known about the exact role of hypermethylation of these genes in pancreatic adenocarcinoma, as the molecular mechanisms underlying these neoplasms remain poorly understood.