Induction of Labor According to Medical Indications: A Critical Evaluation through a Prospective Study

Background: The induction of labor (IOL) is a common obstetric intervention, steadily increasing (one out four pregnancies) in the last years. This procedure should be considered only when there is a medical indication, and when the benefits outweigh the maternal and/or fetal risks of waiting for spontaneous onset of labor. Therefore, this study aims to compare the efficacy of the IOL in terms of induction to delivery time, mode of delivery, and neonatal well-being among different evidence-based and non-evidence-based indications. Methods: This prospective study was conducted at the University Hospital of Modena, between January and December 2020. We included singleton pregnant women undergoing IOL, at the term. Intrauterine deaths, small for gestational age fetuses <5th centile as well women with hypertensive disorders were excluded. Women have been subdivided into 3 groups based on the indication to IOL: premature rupture of membranes (PROM), post-date pregnancy (>41 weeks + 3 days), and non-evidence-based indications (NEBI). The primary outcome is the time occurring between IOL and delivery (TIME), analyzing separately by parity. Moreover, mode of delivery and neonatal wellbeing were evaluated. Results: A total of 585 women underwent IOL in the study period. Overall, the median TIME between IOL and delivery was 19 hours, and the mean cesarean section CS rate was 15.5% (91/585). Pregnancies induced for postdate and non-evidencebased indications registered respectively a significantly higher mean time (p < 0.001), compared with women induced for PROM. This occurred both in nulliparous and multiparous women. Moreover, at multivariate analysis, the IOL TIME ≥24 hours was significantly influenced by Bishop score (p = 0.000) and NEBI (p = 0.02) in nulliparous and by gestational age (p = 0.000) and NEBI (p = 0.02) in multiparous. Moreover, CS rate was significantly influenced by Bishop score (p = 0.003) in nulliparous and by gestational age (p = 0.01) in multiparous. Finally, neonatal intensive care unit (NICU) admission resulted significantly influenced only by gestational age (p = 0.002) in multiparous. Conclusions: Our study confirms that IOL in non-evidence-based indications, leads to an increase in induction to delivery time comparing with women induced for PROM, both in nulliparous and multiparous women, thus it should be justified and carefully evaluated. Further randomized controlled trials (RCT) conducted in European/Italian settings are needed to determine the perinatal outcomes of IOL in non-evidence-based indications

First-trimester prediction of gestational hypertension through the bioelectrical impedance analysis of the body composition

OBJECTIVE: Obesity is a risk factor for the development of gestational hypertension, with important consequences for both the mother and fetus. This prospective observational study aims to propose an early prediction model of hypertensive disorders in pregnancy among obese women, through the bioelectrical impedance analysis (BIA) at the first trimester, thus allowing early recognition of obese women that are at risk to develop gestational hypertension, in order to target preventive interventions. PATIENTS AND METHODS: Singleton obese women (BMI ≥ 30 kg/m2) between the 9th and 12th week of pregnancy were included in the study. The exclusion criteria were chronic diseases, like type 2 diabetes mellitus, hypertension, and other medical pre-existing conditions. Eligible women were followed up at 20, 28, and 36 weeks of gestation by measuring blood pressure, weight, and body composition with the use of the BIA. The diagnosis of gestational hypertension was made after the 20th week of gestation. Pregnancy and perinatal outcomes were then recorded. RESULTS: Of the 479 women included in the study, 85 (17.7%) developed gestational hypertension; the remaining 394 (82.3%) resulted to be normotensive. A higher rate of nulliparous women was found in the hypertensive group (50.6% vs. 37.6%, p = 0.02), together with a higher rate of induction of labor (55.3% vs. 40.9%, p = 0.02) and of small for gestational age (SGA) newborns (12.9% vs. 6.9%, p = 0.03). Significant differences emerged in the body composition between the two groups already from the first trimester, indeed women developing gestational hypertension showed elevated values of Total body Mass, FM, FFM, TBW (p < 0.02), and of leg's FM, FFM (p < 0.006). At the multivariate logistics regression, the risk of developing gestational hypertension resulted higher in women with elevated total body water levels in the first trimester (OR 1.10 95% CI 1.04 -1.92). CONCLUSIONS: The BIA is a rapid, easy, non-invasive, and inexpensive tool to evaluate the body composition of obese pregnant women. It represents a promising predictor of hypertensive disorders in pregnancy, which allows an early identification of the patients at risk of developing gestational hypertension, thus opening a window of opportunity for strictly monitoring and target preventive intervention

Long-term intensive endurance exercise training is associated to reduced markers of cellular senescence in the colon mucosa of older adults

Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence—a state of irreversible growth arrest—is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly higher in the colon mucosa of middle-aged and older overweight adults than in young sedentary individuals, but this upregulation was significantly blunted in age-matched endurance runners. Interestingly, we observe a linear correlation between the level of p16 and the triglycerides to HDL ratio, a marker of colon adenoma risk and cardiometabolic dysfunction. Our data suggest that chronic high-volume high-intensity endurance exercise can play a role in preventing the accumulation of senescent cells in cancer-prone tissues like colon mucosa with age. Future studies are warranted to elucidate if other tissues are also affected, and what are the molecular and cellular mechanisms that mediate the senopreventative effects of different forms of exercise training

Intramammary administration of platelet concentrate as an unconventional therapy in bovine mastitis: first clinical application

Bovine udder infections induce a variety of changes in gene expression of different growth factors that may suggest their possible role in glandular tissue protection or repair processes. Growth factors and also chemokines and cytokines may act synergistically to increase the infiltration of neutrophils and macrophages to promote angiogenesis, fibroplasia, matrix deposition, and, ultimately, re-epithelialization. Considering the vast applications, typically in human medicine, of platelet concentrate (PC) and its ease of preparation, the aim of our study was to evaluate an alternative therapy to stimulate the regeneration of glandular tissue, administering a concentration in excess of the growth factors contained in the PC. In each one of the 3 farms examined in the trial, PC was prepared from donor cows in good health, free from infections, and with no records of medications administered during the previous 2 mo. The platelet produced in one farm was used only for treating the cows of the same farm in a heterologous way. A total of 229 mastitic quarters were divided in 3 groups: antibiotic group (treated with intramammary antibiotic), antibiotic and PC group (treated intramammarily with antibiotics in association with PC), and PC group (treated with intramammary PC alone). The diagnosis of mastitis was based on somatic cell count and bacteriological evaluation of the milk from the affected quarter. Platelet concentrate, alone or in association with antibiotic, was used for 3 consecutive days as an unconventional therapy in bovine acute and chronic mastitis. Our data show that the associated action of antibiotic and PC performed significantly better than the antibiotic alone, either for the recovery of the affected mammary quarters or for somatic cell count reduction. In the same way, the association antibiotic plus PC showed significantly fewer relapses compared with the antibiotic alone, either for acute or chronic mastitis. The treatment with only PC did not show statistically significant differences compared with both antibiotic alone or associated treatment for acute mastitis, and it was better than the use of only antibiotic for chronic mastitis. Our results show that PC alone may be useful for a quick resolution of the inflammatory response, playing a role in limiting the tissue damage to the mammary gland parenchyma and reducing the recurrence rates

Use of Telemedicine Healthcare Systems in Children and Adolescents with Chronic Disease or in Transition Stages of Life: Consensus Document of the Italian Society of Telemedicine (SIT), of the Italian Society of Preventive and Social Pediatrics (SIPPS), of the Italian Society of Pediatric Primary Care (SICuPP), of the Italian Federation of Pediatric Doctors (FIMP) and of the Syndicate of Family Pediatrician Doctors (SIMPeF)

Telemedicine is considered an excellent tool to support the daily and traditional practice of the health profession, especially when referring to the care and management of chronic patients. In a panorama in which chronic pathologies with childhood onset are constantly increasing and the improvement of treatments has allowed survival for them into adulthood, telemedicine and remote assistance are today considered effective and convenient solutions both for the chronic patient, who thus receives personalized and timely assistance, and for the doctors, who reduce the need for direct intervention, hospitalizations and consequent management costs. This Consensus document, written by the main Italian Scientific Societies involved in the use of telemedicine in pediatrics, has the objectives to propose an organizational model based on the relationships between the actors who participate in the provision of a telemedicine service aimed at minors with chronic pathologies, identifying specific project links between the areas of telemedicine in the developmental age from the first 1000 days of life to the age adult. The future scenario will have to be able to integrate digital innovation in order to offer the best care to patients and citizens. It will have to be able to provide the involvement of patients from the very beginning of the design of any care pathway, increasing where possible the proximity of the health service to citizens

Recoil Proton Telescopes and Parallel Plate Avalanche Counters for the 235^{235}U(n,f) cross section measurement relative to H(n,n)H between 10 and 450 MeV neutron energy

With the aim of measuring the $^{235}$U(n,f) cross section at the n\_TOF facility at CERN over a wide neutron energy range, a detection system consisting of two fission detectors and three detectors for neutron flux determination was realized. The neutron flux detectors are Recoil Proton Telescopes (RPT), based on scintillators and solid state detectors, conceived to detect recoil protons from the neutron-proton elastic scattering reaction. This system, along with a fission chamber and an array of parallel plate avalanche counters for fission event detection, was installed for the measurement at the n\_TOF facility in 2018, at CERN. An overview of the performances of two RPTs - especially developed for this measurement - and of the parallel plate avalanche counters are described in this article. In particular, the characterization in terms of detection efficiency by Monte Carlo simulations and response to neutron beam, the study of the background, dead time correction and characterization of the samples, are reported. The results of the present investigation show that the performances of these detectors are suitable for accurate measurements of fission reaction cross sections in the range from 10 to 450~MeV

Action of MK‐7264 (Gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation

Background & Purpose The P2X3 receptor is an ATP‐gated ion channel expressed by sensory afferent neurons, and is as a target to treat chronic sensitisation conditions. The first‐in‐class, selective P2X3 and P2X2/3 receptor antagonist, the diaminopyrimidine MK‐7264 (Gefapixant), has progressed to Phase III trials for refractory or unexplained chronic cough. We have used patch‐clamp to elucidate the pharmacology and kinetics of MK‐7264 and rat models of hypersensitivity and hyperalgesia to test efficacy in these conditions. Experimental Approach Whole‐cell patch‐clamp of 1321N1 cells expressing human P2X3 and P2X2/3 receptors was used to determine mode of MK‐7264 action, potency and kinetics. The analgesic efficacy was assessed using paw withdrawal threshold and limb weight distribution in rat models of inflammatory, osteoarthritic and neuropathic sensitisation. Key Results MK‐7264 is a reversible allosteric antagonist at human P2X3 and P2X2/3 receptors with IC50 values of 153 and 220nM, respectively. Experiments with the slowly desensitising P2X2/3 heteromer revealed concentration and state‐dependency to wash‐on, with faster rates and greater inhibition when applied before agonist compared to during agonist application. Wash‐on rate (τ value) for MK‐7264 at maximal concentrations was 19s and 146s when applied before and during agonist application, respectively. In vivo, MK‐7264 (30 mg/kg) displayed efficacy comparable to naproxen (20 mg/kg) in inflammatory and osteoarthritic sensitisation models, and gabapentin (100 mg/kg) in neuropathic sensitisation models, increasing paw withdrawal threshold and decreasing weight bearing discomfort. Conclusions and Implications MK‐7264 is a reversible and selective P2X3 and P2X2/3 antagonist, exerting allosteric antagonism via preferential activity at closed channels. Efficacy in rat models supports clinical investigation of chronic sensitisation conditions