Substandard application of preimplantation genetic screening may interfere with its clinical success

The intent of this study was to evaluate a recent randomized clinical trial evaluating the effect of preimplantation genetic screening (PGS) that reports a negative effect on pregnancy outcome. This article reviews appropriate PGS techniques and how they differ from the trial in question. A closer look at the clinical trial in question reveals significant lack of expertise in biopsy, cell fixation, genetic analysis, and patient selection. At most, this trial demonstrates that in inexperienced hands, PGS can be detrimental. No other conclusions concerning the effect of PGS on pregnancy results can be drawn from the trial.     

Mortality for newborns of birthweight less than 1500 g in Spanish neonatal units (2002-2005)

The purpose of this study was to analyze the mortality and its prognostic factors in a Spanish cohort of very low birthweight (VLBW) infants during the period 2002 to 2005. Using the Spanish Society of Neonatology database (SEN 1500), 8942 infants with a birthweight < 1500 g were recruited. The overall mortality was 17.3%. However, this incidence underwent a significant decrease over the study period, from 19.4% in 2002 to 15.2% in 2005 ( P = 0.003). Mortality ranged from 12.4% in 25% of the participating neonatal units to 19.4% in a further 25%. Mortality was higher in outborn infants (25.8%) than in inborn infants (16.6%) ( P < 0.001). The mortality rates of these neonates are also presented by 100-g intervals (401 to 1500) and for the different hospitalization times: in the delivery room, within 24 hours and 28 days of birth, at 36 weeks of postmenstrual age, and on discharge. Of note was that mortality was greatest within 24 hours and 28 days of birth in each of the weight groups ( P < 0.001). In conclusion, in the cohort of infants < 1500 g examined, mortality in the period from 2002 to 2005 was still high, especially among newborns weighing < 1000 g. We did, however, observe a decreasing trend in mortality rates for the participating neonatal units over the 4 study years. Our findings highlight the need to promote intrauterine transport and improve neonatal transport as well as the management of these infants in the delivery room and within the first 28 days of life.     

Solid pseudopapillary tumor of the pancreas. A report of 3 cases and a review of the literature

Solid pseudopapillary tumours of the pancreas (SPTP) are a distinct clinico-pathological entity that differs from the other cystic pancreatic neoplasms in the young age of onset, the almost exclusive incidence in the female sex and the low degree of malignancy. SPTP is a rare neoplasm that has shown a progressive increase of incidence, passing from 0.17%-2.7% of all exocrine tumours of the pancreas in the 1980's, to 6% in recent reports in 2003. In addition, it accounts for about 5% of cystic neoplasms of the pancreas. With the present paper, in the world literature, updated to August 2005, 887 cases have been described in 248 articles. The histogenesis of these epithelial neoplasms remains uncertain though it is likely that they originate from pluripotent immature pancreatic cells. The tumour is generally of large size and invariably presents a capsule. The diagnosis in most cases is based on compressive symptoms, pain or finding of a palpable mass, while in about 20% of the patients the finding is occasional during abdominal imaging performed for other pathologies. CT and MR are not always sufficient to differentiate with certainty between this type of tumour and other cystic neoplasms of the pancreas such as pseudocysts, parasitic cysts and congenital cysts. Cytological examination in most cases permits the diagnosis of SPTP. The malignancy of these neoplasms is attenuated and local with capsular invasion, lymp-node spread and, only rarely, liver and peritoneal metastases. The surgical treatment has to be radical since the malignancy can only be defined by postoperative histological examination. The treatment consists of three possible options: duodenocephalopancreatectomy, intermediate pancreatectomy, and distal pancreatectomy with or without splenectomy. Intraoperative histological examination is mandatory for the diagnostic confirmation and for the evaluation of negativity of the pancreatic resection margins. Survival after radical resection is excellent. Moreover, in forma metastasizing to the liver an aggressive attitude may be still curative and assure longer survival. The Authors report their experience with three female patients with an average age 18 years (28,19 and 8 years) operated on between 1995 and 2000 for SPTP. Two of the patients were asymptomatic and the finding of the tumour was occasional. The third patient presented jaundice and abdominal pain. The average diameter of the tumours was 6 cm (4, 7 and 7 cm). In all three cases tumour marker values (CEA, Ca19-9, alphaFP) were normal. Only in one case was the preoperative diagnosis correct. The surgical treatment depended on the location of the neoplasms: for the two tumours in the head, in one case an enucleoresection was performed in relation to an exophytic location, while, in the other, a duodenocephalopancreatectomy was performed. In the somatopancreatic tumour a distal splenopancreatectomy was performed. Only in one case (the DCP) the capsule and the surrounding parenchyma were infiltreted by neoplasm. In all cases there was immunohistochemical positivity for alpha1-antitrypsin and for neuron-specific enolase. Neither mortality nor operative morbidity were observed. Follow-up with CT found no relapses in any of the three patients after 5, 7 and 10 years, respectively, after the operation.     

Cardiovascular Safety and Effectiveness of Bisphosphonates: From Intervention Trials to Real-Life Data

Both osteoporosis with related fragility fractures and cardiovascular diseases are rapidly outspreading worldwide. Since they are often coexistent in elderly patients and may be related to possible common pathogenetic mechanisms, the possible reciprocal effects of drugs employed to treat these diseases have to be considered in clinical practice. Bisphosphonates, the agents most largely employed to decrease bone fragility, have been shown to be overall safe with respect to cardiovascular diseases and even capable of reducing cardiovascular morbidity in some settings, as mainly shown by real life studies. No randomized controlled trials with cardiovascular outcomes as primary endpoints are available. While contradictory results have emerged about a possible BSP-mediated reduction of overall mortality, it is undeniable that these drugs can be employed safely in patients with high fracture risk, since no increased mortality has ever been demonstrated. Although partial reassurance has emerged from meta-analysis assessing the risk of cardiac arrhythmias during bisphosphonates treatment, caution is warranted in administering this class of drugs to patients at risk for atrial fibrillation, possibly preferring other antiresorptives or anabolics, according to osteoporosis guidelines. This paper focuses on the complex relationship between bisphosphonates use and cardiovascular disease and possible co-management issues.     

Effectiveness of influenza vaccination in preventing influenza in primary care,Navarre, Spain, 2021/22

Compared with individuals unvaccinated in the current and three previous influenza seasons, in 2021/22, influenza vaccine effectiveness at primary care level was 37% (95% CI: 16 to 52) for current season vaccination, regardless of previous doses, and 35% (95% CI: −3 to 45) for only previous seasons vaccination. Against influenza A(H3N2), estimates were 39% (95% CI: 16 to 55) and 24% (95% CI: −8 to 47) suggesting moderate effectiveness of current season vaccination and possible remaining effect of prior vaccinations.     

Gut Microbiota in Psoriasis

Psoriasis is a chronic inflammatory skin disease with autoimmune pathogenic characteristics and is caused by chronic inflammation, which results in uncontrolled keratinocyte growth and defective differentiation. The link between the gut microbiota and immune system regulation opened a novel angle to understand the pathogenesis of many chronic multifactorial diseases, including psoriasis. Current evidence suggests that modulation of the gut microbiota, both through dietary approaches and through supplementation with probiotics and prebiotics, could represent a novel therapeutic approach. The present work aims to highlight the latest scientific evidence regarding the microbiome alterations of psoriatic patients, as well as state of the art insights in terms of microbiome-targeted therapies as promising preventive and therapeutic tools for psoriasis.     

Synthesis and in vivo studies of the stereoisomers of N-[11C]methyl-homoepibatidine

The carbon-11 labeled enantiomers of nicotinic acetylcholine receptor (nAChR) ligand N-[11C]methyl-homoepibatidine have been synthesized to study the neuronal nicotinic acetylcholine receptors (nAChRs).In vivo evaluations were performed in mice and pig using positron emission tomography (PET). The radioligands displayed a strong enantioselectivity. The (-)-enantiomer showed high uptake in the brain while the (+)-enantiomer was rapidly washed out. In metabolite studies in mice >65% unchanged ligand was found in the blood after 60 minutes. No metabolites were found in the brain. After intravenous application of N-[11C]methyl-(-)-homoepibatidine in the pig specific accumulation in the thalamus was seen. Blocking experiments with cytisine showed specific binding consistent with labeling of the alpha4beta2-nAChR-subtype in the brain. Quantitative kinetic modeling of radiotracers in the pig brain was performed using the arterial input function. The brain uptake of the (-)-isomer was best fitted by a three-compartment model. High distribution volumes were found in the thalamus (DV(TOT) = 66.617, DV(S) = 59.910) versus a low uptake in the cerebellum (DV(TOT) = 8.605m, DV(S) = 1.898). The binding characteristics suggest N-[11C]methyl-(-)-homoepibatidine to be suited for PET imaging studies, but high toxicity prevents routine use in humans.