The Role of BCL2 Family of Apoptosis Regulator Proteins in Acute and Chronic Leukemias

The disturbance of apoptosis molecular signaling pathways is involved in carcinogenesis. BCL2 family of proteins is the hallmark of apoptosis regulation. In the last decade, new members of BCL2 gene family were discovered and cloned and were found to be differentially expressed in many types of cancer. BCL2 protein family, through its role in regulation of apoptotic pathways, is possibly related to cancer pathophysiology and resistance to conventional chemotherapy. It is well known that leukemias are haematopoietic malignancies characterized by biological diversity, varied cytogenetics, different immunophenotype profiles, and diverse outcome. Current research focuses on the prognostic impact and specific role of these proteins in the pathogenesis of leukemias. The understanding of the molecular pathways that participate in the biology of leukemias may lead to the design of new therapies which may improve patients' survival. In the present paper, we describe current knowledge on the role of BCL2 apoptosis regulator proteins in acute and chronic leukemias

Insulin-Like Growth Factor (IGF)-I and Insulin in Normal and Growth-Restricted Mother/Infant Pairs

Insulin-like growth factor (IGF)-I and insulin are essential for fetal growth. We investigated perinatal changes of both factors in 40 mothers and their 20 appropriate-for-gestational-age (AGA) and 20 intrauterine-growth-restricted (IUGR) fetuses and neonates on day 1 (N1) and day 4 (N4) postpartum. Fetal and N1, but not N4, IGF-I levels were increased in AGA (P < .001 and P = .037, resp.). N1 insulin levels were lower in IUGR (P = .048). Maternal, fetal, and N1 IGF-I, and fetal insulin levels positively correlated with customized centiles (r = .374, P = .035, r = .608, P < .001, r = .485, P = .006, and r = .654, P = .021, resp.). Female infants presented elevated fetal and N4 IGF-I levels (P = .023 and P = .016, resp.). Positive correlations of maternal, fetal, and neonatal IGF-I levels, and fetal insulin levels with customized centiles underline implication of both hormones in fetal growth. IUGR infants present gradually increasing IGF-I levels. Higher IGF-I levels are documented in females

Perinatal Plasma Monocyte Chemotactic Protein-1 Concentrations in Intrauterine Growth Restriction

Monocyte-chemotactic-protein-1 (MCP-1) plays vital roles in immune response, angiogenesis, and pregnancy outcome. We investigated plasma MCP-1 concentrations in 40 mothers and their 20 intrauterine-growth-restricted (IUGR) and 20 appropriate-for-gestational-age (AGA) fetuses and neonates on postnatal days 1 (N1) and 4 (N4). Maternal and fetal MCP-1 concentrations were decreased (P<001 and P = .018, resp.), whereas N1 MCP-1 concentrations were elevated in IUGR group (P = .012). In both groups, fetal MCP-1 concentrations were lower compared to N1 and N4 ones (P = .045, P = .012, resp., for AGA, P < .001 in each case for IUGR). Reduced maternal and fetal MCP-1 concentrations in IUGR may reflect failure of trophoblast invasion, suggesting that down-regulation of MCP-1 may be involved in the pathogenesis of IUGR. Increased MCP-1 concentrations in IUGR neonates and higher postnatal ones in all infants may be attributed to gradual initiation of ex utero angiogenesis, which is possibly enhanced in IUGR

Calcium Channel Blockers and Esophageal Sclerosis: Should We Expect Exacerbation of Interstitial Lung Disease?

Esophageal sclerosis is the most common visceral manifestation of systemic sclerosis, resulting in impaired esophageal clearance and retention of ingested food; in addition, co-existence of lung fibrosis with esophageal scleroderma is not uncommon. Both the progression of generalized connective tissue disorders and the damaging effect of chronic aspiration due to esophageal dysmotility appear to be involved in this procedure of interstitial fibrosis. Nifedipine is a widely prescribed calcium antagonist in a significant percentage of rheumatologic patients suffering from Raynaud syndrome, in order to inhibit peripheral vasospasm. Nevertheless, blocking calcium channels has proven to contribute to exacerbation of gastroesophageal reflux, which consequently can lead to chronic aspiration. We describe the case of severe exacerbation of interstitial lung disease in a 76-year-old female with esophageal sclerosis who was treated with oral nifedipine for Raynaud syndrome

Compliance with evidence-based clinical guidelines in the management of acute biliary pancreatitis: the MANCTRA-1 study protocol.

Despite existing evidence-based practice guidelines for the management of biliary acute pancreatitis (AP), the clinical compliance with recommendations is overall poor. Studies in this field have identified significant discrepancies between evidence-based recommendations and daily clinical practice. The most commonly reported gaps between clinical practice and AP guidelines include the indications for CT scan, need and timing of artificial nutritional support, indications for antibiotics, and surgical/endoscopic management of biliary AP. The MANCTRA-1 (coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis) study is aiming to identify the areas for quality improvement that will require new implementation strategies. The study primary objective is to evaluate which items of the current AP guidelines are commonly disregarded and if they correlate with negative clinical outcomes according to the different clinical presentations of the disease. We attempt to summarize the main areas of sub-optimal care due to the lack of compliance with current guidelines to provide the basis for introducing a number of bundles in AP patients' management to be implemented during the next years. The MANCTRA-1 study is an international multicenter, retrospective cohort study with the purpose to assess the outcomes of patients admitted to hospital with a diagnosis of biliary AP and the compliance of surgeons worldwide to the most up-to-dated international guidelines on biliary AP. ClinicalTrials.Gov ID Number: NCT04747990, Date: February 23, 2021. Protocol Version V2.2

Preoperative diagnosis of obscure gastrointestinal bleeding due to a GIST of the jejunum: a case report

Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms affecting the digestive tract or nearby structures within the abdomen. We present a case of a 66-year-old female patient who presented with obscure anemia due to gastrointestinal bleeding and underwent exploratory laparotomy during which a large GIST of the small intestine was discovered. Examining the preoperative results of video capsule endoscopy, computed tomography, and angiography and comparing them with the operative findings we discuss which of these investigations plays the most important role in the detection and localization of GIST. A sort review of the literature is also conducted on these rare mesenchymal tumours

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)