Does high molecular weight-hyaluronic acid prevent hormone-induced preterm labor in rats?

OBJECTIVE: The aim of our study was to test if oral high hyaluronic acid (HMW-HA) administration was effective in contrasting induced preterm birth (PTB) in female Wistar rats. MATERIALS AND METHODS: A total of 24 pregnant rats were pretreated with placebo or low (2.5 mg/day)/high dose (5 mg/day) of HMW-HA (day 15) and then induced to delivery with mifepristone plus prostaglandin E2 (PGE2) (3 mg/100 µL + 0.5 mg/animal) on the 19th day of pregnancy. The delivery time was recorded and the messenger RNA (mRNA) levels of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)1ß, IL-6] were detected in the uterine tissues by real-time polymerase chain reaction (real PCR). Immunohistochemistry was performed alongside. RESULTS: Oral HMW-HA was well absorbed in the body and was able to significantly delay the timing of delivery and decrease mRNA synthesis of pro-inflammatory cytokines. CONCLUSIONS: HMW-HA, by acting in the management of PTB, may represent a new approach to protecting physiological pregnancy.

Functional outcomes after transanal total mesorectal excision (TaTME): a random forest analysis to predict patients' outcomes.

PURPOSE: Anorectal, sexual, and urinary dysfunction are common issues after rectal cancer surgery, although seldom explored. The primary aim of this study was to investigate postoperative anorectal functional results. METHODS: Patients with mid/low-rectal cancer treated with transanal TME (TaTME) with primary anastomosis with/without diverting stoma between 2015 and 2020 were reviewed and selected if they had a minimum follow-up of 6 months (from the primary procedure or stoma reversal). Patients were interviewed using validated questionnaires and the primary outcome was bowel function based on Low Anterior Resection Syndrome (LARS) scores. Statistical analyses were performed to identify clinical/operative variables correlated with worse outcomes. A random forest (RF) algorithm was computed to classify patients at a greater risk of minor/major LARS. RESULTS: Ninety-seven patients were selected out of 154 TaTME performed. Overall, 88.7% of the patients had a protective stoma and 25.8% reported major LARS at mean follow-up of 19.0 months. Statistical analyses documented that age, operative time, and interval to stoma reversal correlated with LARS outcomes. The RF analysis disclosed worse LARS symptoms in patients with longer operative time (> 295 min) and stoma reversal interval (> 5.6 months). If the interval ranged between 3 and 5.6 months, older patients (> 65 years) reported worse outcomes. Finally, no statistical difference was documented when comparing the rate of minor/major LARS in the first 27 cases versus others. CONCLUSION: One-quarter of the patients developed major LARS after TaTME. An algorithm based on clinical/operative variables, such as age, operative time, and time to stoma reversal, was developed to identify categories at risk for LARS symptoms.

Size and environment: The effect of phonon localization on micro-Brillouin imaging.

Specifically designed samples have been analyzed to test the ability of Brillouin spectroscopy to provide reliable mechanical characterization of micro and nano-objects. The selected samples are polymeric films, whose transversal sizes from hundreds of nano- to some micro-meters cover the entire range of length-scales relevant in Brillouin scattering process. The experimental data highlight how, the size of the extended collective oscillation (acoustic phonons, in brief) is the lowest spatial resolution reachable in Brillouin mechanical characterization. Conversely, in the limit condition of phonon confinement, the technique provides the mechanical properties of nano-objects whose characteristic size is comparable with the phonon wavelength (⁓300 nm). Investigating acoustically heterogeneous materials, both size of heterogeneity and acoustic mismatch between adjacent regions are shown to be relevant in shaping the Brillouin response. In particular, a transition from a confined to a non-confined condition is obtained modulating the acoustic mismatch between the micro-objects and their local environment. The provided results and the derived analytic models for the data analysis will guide the interpretation of Brillouin spectra acquired in complex nano-structured samples such as cells, tissues or biomimetic materials. Our analysis can therefore generate new insights to tackle fundamental problems in mechanobiology or to characterize new bioengineered materials.

Author Correction: Oral supplementation of α-lipoic acid (ALA), magnesium, vitamin B6 and vitamin D stabilizes cervical changes in women presenting risk factors for preterm birth.

Correction to: European Review for Medical and Pharmacological Sciences 2022; 26 (23): 8879-8886. DOI: 10.26355/eurrev_202212_30560-PMID: 36524507-published online on December 15, 2022. After publication, the authors found out that in Figure 1 a box, including 63 patients included in the final analysis was missing. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/30560.

Oral supplementation of α-lipoic acid (ALA), magnesium, vitamin B6 and vitamin D stabilizes cervical changes in women presenting risk factors for preterm birth.

OBJECTIVE: Recently, the PTB risk has been related to the objective measurement of cervical length (CL), since a CL of less than 25 mm is an accurate predictor of increased risk of PTB. Primary prevention of preterm labor is based on the early identification of symptoms and on pharmacological treatments with tocolytic drugs for inhibition of uterine contractions that are associated with a shortening of the cervix. Unfortunately, most of these drugs have important side effects. PATIENTS AND METHODS: This study aimed to evaluate whether the administration of a combination of oral α-lipoic acid (ALA), magnesium, vitamin B6 and vitamin D to pregnant women presenting risk factors for PTB could reduce the rate of cervical shortening at 19-22 weeks of gestational age. RESULTS: A total of 122 women attending the first-trimester aneuploidy screening at 11-14 weeks of pregnancy and presenting risk factors for PTB were included in the study. Cervical length significantly decreased in the control group compared with the treatment group (-3.86 ± 1.97 vs. 1.50 ± 1.26; p=0.02). Although the rate of preterm birth did not significantly decrease (9.5% vs. 5.1%), admission for threatened PTB was statistically reduced in the treatment group compared with the control group (3.4% vs. 14.3%). CONCLUSIONS: Oral supplementation of ALA, magnesium, vitamin B6 and vitamin D significantly counteracted cervix shortening in pregnant women presenting risk factors for PTB.

New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study.

PURPOSE: Many questions concerning Turner syndrome (TS) remain unresolved, such as the long-term complications and, therefore, the optimal care setting for adults. The primary aim of this long-term cohort study was to estimate the incidence of comorbid conditions along the life course. METHODS: A total of 160 Italian patients with TS diagnosed from 1967 to 2010 were regularly and structurally monitored from the diagnosis to December 2019 at the University Hospital of Bologna using a structured multidisciplinary monitoring protocol. RESULTS: The study cohort was followed up for a median of 27 years (IQR 12-42). Autoimmune diseases were the comorbid condition with the highest incidence (61.2%), followed by osteoporosis and hypertension (23.8%), type 2 diabetes (16.2%) and tumours (15.1%). Median age of onset ranged from 22 years for autoimmune diseases to 39 years for type 2 diabetes. Malignant tumours were the most prominent type of neoplasm, with a cumulative incidence of 11.9%. Papillary thyroid carcinoma was the most common form of cancer, followed by skin cancer and cancer of the central nervous system. Only one major cardiovascular event (acute aortic dissection) was observed during follow-up. No cases of ischaemic heart disease, heart failure, stroke or death were recorded. CONCLUSIONS: This cohort study confirms the need for continuous, structured and multidisciplinary lifelong monitoring of TS, thus ensuring the early diagnosis of important comorbid conditions, including cancer, and their appropriate and timely treatment. In addition, these data highlight the need for the increased surveillance of specific types of cancer in TS, including thyroid carcinoma.

Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.

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.

Proposal for a 6-step approach for differential diagnosis of neonatal erythroderma.

The broad differential diagnosis of neonatal erythroderma often poses a diagnostic challenge. Mortality of neonatal erythroderma is high due to complications of the erythroderma itself and the occasionally severe and life-threatening underlying disease. Early correct recognition of the underlying cause leads to better treatment and prognosis. Currently, neonatal erythroderma is approached on a case-by-case basis. The purpose of this scoping review was to develop a diagnostic approach in neonatal erythroderma. After a systematic literature search in Embase (January 1990 - May 2020, 74 cases of neonatal erythroderma were identified, and 50+ diagnoses could be extracted. Main causes were the ichthyoses (40%) and primary immunodeficiencies (35%). Congenital erythroderma was present in 64% (47/74) of the cases, predominantly with congenital ichthyosis (11/11; 100%), Netherton syndrome (12/14, 86%) and Omenn syndrome (11/23, 48%). Time until diagnosis ranged from 102 days to 116 days for cases of non-congenital erythroderma and congenital erythroderma respectively. Among the 74 identified cases a total of 17 patients (23%) died within a mean of 158 days and were related to Omenn syndrome (35%), graft-versus-host disease (67%) and Netherton syndrome (18%). Disease history and physical examination are summarized in this paper. Age of onset and a collodion membrane can help to narrow the differential diagnoses. Investigations of blood, histology, hair analysis, genetic analysis and clinical imaging are summarized and discussed. A standard blood investigation is proposed, and the need for skin biopsies with lympho-epithelial Kazal-type related Inhibitor staining is highlighted. Overall, this review shows that diagnostic procedures narrow the differential diagnosis in neonatal erythroderma. A 6-step flowchart for the diagnostic approach for neonatal erythroderma during the first month of life is proposed. The approach was made with the support of expert leaders from international multidisciplinary collaborations in the European Reference Network Skin-subthematic group Ichthyosis.

Radiomics in pancreatic neuroendocrine tumors: methodological issues and clinical significance.

PURPOSE: To present the state-of-art of radiomics in the context of pancreatic neuroendocrine tumors (PanNETs), with a focus on the methodological and technical approaches used, to support the search of guidelines for optimal applications. Furthermore, an up-to-date overview of the current clinical applications of radiomics in the field of PanNETs is provided. METHODS: Original articles were searched on PubMed and Science Direct with specific keywords. Evaluations of the selected studies have been focused mainly on (i) the general radiomic workflow and the assessment of radiomic features robustness/reproducibility, as well as on the major clinical applications and investigations accomplished so far with radiomics in the field of PanNETs: (ii) grade prediction, (iii) differential diagnosis from other neoplasms, (iv) assessment of tumor behavior and aggressiveness, and (v) treatment response prediction. RESULTS: Thirty-one articles involving PanNETs radiomic-related objectives were selected. In regard to the grade differentiation task, yielded AUCs are currently in the range of 0.7-0.9. For differential diagnosis, the majority of studies are still focused on the preliminary identification of discriminative radiomic features. Limited information is known on the prediction of tumors aggressiveness and of treatment response. CONCLUSIONS: Radiomics is recently expanding in the setting of PanNETs. From the analysis of the published data, it is emerging how, prior to clinical application, further validations are necessary and methodological implementations require optimization. Nevertheless, this new discipline might have the potential in assisting the current urgent need of improving the management strategies in PanNETs patients.

Role of fluctuations in epidemic resurgence after a lockdown.

Most popular statistical models in epidemic evolution focus on the dynamics of average relevant quantities and overlooks the role of small fluctuations on the model parameters. Models for Covid-19 are no exception. In this paper we show that the role of time-correlated fluctuations, far from being negligible, can in fact determine the spreading of an epidemic and, most importantly, the resurgence of the exponential diffusion in the presence of time-limited episodes in promiscuity behaviours. The results found in this work are not only relevant and specific for the Covid-19 epidemic but are more general and can be applied to other epidemics.

Chloracne: a case series on cutaneous expression of CYP1A1 as diagnostic biomarker.

Chloracne, also known as metabolizing acquired dioxin-induced skin hamartomas (MADISH), is a rare disfiguring disease related to dioxin exposure. There is a paucity of literature on the clinical manifestations and pathogenesis of chloracne/MADISH. The aim of this study was to assess the clinical features of this very unusual acneiform eruption and to explore the pathogenesis of the disease. This was a retrospective, observational report study was conducted on five patients belonging to the same nuclear family (father, mother and three children) and a relative (father's brother) living in the same house. Histopathological, immunohistochemical, laboratory and toxicological analyses were performed for all patients. The results suggest that CYP1A1 in human skin is a diagnostic biomarker in chloracne, and was positive for all the patients in our sample. Tetrachlorodibenzo-p-dioxin is the most investigated dioxin responsible for chloracne; however, several other agonists, whether dioxin-like or not, can activate the aryl hydrocarbon receptor. To our knowledge, this Italian case series is the first study to suggest polychlorinated biphenyls as a possible cause of an overstimulation of aryl hydrocarbons causing the consequent acneiform eruption.

'Colouring' wipes phenomenon: a peculiar skin pigmentation induced by ascorbic acid observed during lockdown.

During the SARS-CoV-2 (COVID-19) pandemic, an unusual outbreak of yellow-brown pigmentation on the skin of children was reported. Because of the restrictions on movement promulgated during the lockdown, most consultancies were performed using teledermatology. Data concerning personal care products and application of topical substances were collected, which revealed use of the same brand of wipes for all patients. A liquid chromatography-mass spectrometry analysis was performed to compare the components of the wipes before and after the observation of the pigmentation, in order to detect the responsible substance. This analysis revealed a level about 10-fold higher than normal of ascorbic acid and its oxidation products (dehydroascorbic acid and L-threonic acid) in the wipes associated with the pigmentation. These 'colouring wipes' represent a peculiar but harmless phenomenon that highlights the importance of careful questioning about personal care products used by patients.