Endothelial injury and dysfunction with emerging immunotherapies in multiple myeloma, the impact of COVID-19, and endothelial protection with a focus on the evolving role of defibrotide.

Patients with multiple myeloma (MM) were among the groups impacted more severely by the COVID-19 pandemic, with higher rates of severe disease and COVID-19-related mortality. MM and COVID-19, plus post-acute sequelae of SARS-CoV-2 infection, are associated with endothelial dysfunction and injury, with overlapping inflammatory pathways and coagulopathies. Existing treatment options for MM, notably high-dose therapy with autologous stem cell transplantation and novel chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engaging antibodies, are also associated with endothelial cell injury and mechanism-related toxicities. These pathologies include cytokine release syndrome (CRS) and neurotoxicity that may be exacerbated by underlying endotheliopathies. In the context of these overlapping risks, prophylaxis and treatment approaches mitigating the inflammatory and pro-coagulant effects of endothelial injury are important considerations for patient management, including cytokine receptor antagonists, thromboprophylaxis with low-molecular-weight heparin and direct oral anticoagulants, and direct endothelial protection with defibrotide in the appropriate clinical settings.

Use of defibrotide in COVID-19 pneumonia: comparison of a phase II study and a matched real-world cohort control.

The coronavirus disease 2019 (COVID-19) pandemic led to an unprecedented burden on healthcare systems around the world and a severe global socioeconomic crisis, with more than 750 million confirmed cases and at least 7 million deaths reported by 31st December 2023. The DEFI-VID19 study (ClinicalTrials.gov NCT04335201), a phase II, single-arm, multicenter, open-label trial was designed in mid-2020 to assess the safety and efficacy of defibrotide in treating patients with COVID-19 pneumonia. Defibrotide was administered at a dose of 25 mg/kg/d intravenously, divided into four daily doses over a planned 14-day period for patients with COVID-19 pneumonia receiving non-invasive ventilation. The primary endpoint was Respiratory Failure Free Survival (RFFS); Overall Survival (OS), the number of post-recovery days, and adverse events were the secondary endpoints. For comparison, a contemporaneous control cohort receiving standard of care only was retrospectively selected by applying the eligibility criteria of the DEFI-VID19 trial. To adjust for the imbalance between the two cohorts in terms of baseline variable distributions, an outcome regression analysis was conducted. In adjusted analysis, patients receiving defibrotide reported a trend towards higher RFFS (HR=0.71[0.95CI: 0.34 to 1.29, P= .138]) and OS (HR=0.78[0.95CI: 0.33 to 1.53, P= .248]) and showed a significantly increased number of post-recovery days (difference in means: 3.61[ 0.95CI: 0.97 to 6.26, P= .0037]). Despite concomitant thromboprophylaxis with low molecular weight heparin, the safety profile of defibrotide proved to be favorable. Taken together, our findings suggest that defibrotide may represent a valuable addition to the COVID-19 therapeutic options.

Baseline circulating tumour DNA and interim PET predict response in relapsed/refractory classical Hodgkin lymphoma.

Reliable biomarkers for early identification of treatment failure in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL) are lacking. Circulating tumour DNA (ctDNA) profiling has emerged as a powerful predictive and prognostic tool in several haemopoietic and non-haemopoietic malignancies and may guide rational treatment choices in r/r cHL. To assess the predictive and prognostic value of ctDNA, we performed a retrospective analysis on 55 r/r cHL patients treated with the bendamustine, gemcitabine and vinorelbine (BEGEV) regimen and additionally evaluated the potential utility of integrating ctDNA with interim [18 F]-FDG positron emission tomography (iPET). Baseline ctDNA genotyping in r/r cHL mirrored gene mutations and pathways involved in newly diagnosed cHL. We found that baseline ctDNA quantification and serial ctDNA monitoring have prognostic value in r/r cHL receiving salvage chemotherapy. Lastly, integrating ctDNA quantification with iPET evaluation may improve the early identification of patients at high risk of failing standard salvage therapy, who may benefit from an early switch to immunotherapeutic agents. Collectively, our results support the implementation of non-invasive methods to detect minimal residual disease in recurrent cHL and justify its prospective evaluation in appropriately designed clinical trials.

Outcome after chimeric antigen receptor (CAR) T-cell therapy failure in large B-cell lymphomas.

This study retrospectively evaluated the outcome of salvage therapy in 51 patients who failed axicabtagene ciloleucel or tisagenlecleucel for relapsed/refractory large B-cell lymphomas. Of these patients, 22 (43%) were enrolled in clinical trials (glofitamab or loncastuximab tesirine + ibrutinib), whereas 29 received standard therapies (lenalidomide [Len], checkpoint inhibitors [CPIs], ibrutinib [I], chemoimmunotherapy and radiotherapy) or supportive care. Overall, 26 of 39 (67%) treated patients received a treatment based on immunotherapy (glofitamab, CPI, Len) that was mainly represented by bispecific antibody (n = 18). In this subgroup, plasma samples were collected and analysed for circulating tumour DNA (ctDNA) using cancer-personalized profiling by deep sequencing (CAPP-seq). The study found that patients with high ctDNA had poor outcomes. At a median follow-up of 11.7 months, the estimated 12-month overall survival (OS) was 35%. Factors adversely affecting the prognosis in the multivariable model were the absence of response to CAR T-cell therapy (HR: 3.08; p = 0.0109) and a diagnosis other than PMBCL and t-FL (HR: 4.54; p = 0.0069). The outcome of patients failing CAR T cells is poor and requires further investigation.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 IgG Is Present in the Amniotic Fluid of both Infected and Vaccinated Women at Second Trimester of Pregnancy: A Cohort Study.

INTRODUCTION: Pregnant women are protected from the complications of COVID-19 infection, thanks to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. The benefit of this vaccination to prevent morbidity and mortality in the fetus has not yet been completely elucidated. Our aim was to test the presence of anti-SARS-CoV-2 antibodies in the amniotic fluid during the second trimester of pregnancy and then to compare them to the antibody levels in maternal serum to evaluate their correlation and to improve amniotic fluid immunological characteristics knowledge. METHODS: This cohort study took place at the Policlinico G. Martino of Messina from September 2021 to February 2022; 22 pregnant women had amniocentesis: we analyzed serum and amniotic fluid samples of women who contracted the SARS-CoV-2 infection or vaccinated against the same virus within 1 year, and women never infected or vaccinated against it. Amniotic fluids and peripheral blood were collected to evaluate IgG anti-SARS-CoV-2 nucleocapsid and spike S1 protein antibodies. RESULTS: Patients vaccinated had higher S1 receptor-binding domain antibody levels both in amniotic fluid (p < 0.006; mean 68.70; standard deviation [SD] 85.46) and maternal blood (p < 0.005; mean 1,989.86; SD 3,777.15) than unvaccinated women. Anti-nucleocapsid antibodies were present in women who developed COVID infection both in amniotic fluid and maternal blood but not in unvaccinated women. There was a high correlation between the concentrations of anti-spike antibody levels in serum and amniotic fluid of vaccinated women (p < 0.001; R = 1.0) and of anti-nucleocapsid antibody levels in serum and amniotic fluid of women who developed COVID infection (p < 0.001; R = 0.93). CONCLUSION: Recent studies have shown that SARS-CoV-2 vaccination during pregnancy is safe. Moreover, we can assume that there is an early transplacental antibody transfer after anti-SARS-CoV-2 immunization to protect the fetus, and there is also a high correlation between levels of anti-nucleocapsid antibodies in blood and amniotic fluid of pregnant women previously infected.

Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design.

AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme. METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up. CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines. CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).

Immediate Implant and Customized Healing Abutment Promotes Tissues Regeneration: a 5-year Clinical Report.

INTRODUCTION: Significant alveolar bone resorption follows tooth extraction. Immediate implant placement alone is not sufficient to prevent this phenomenon. CASE PRESENTATION: In this clinical case, a fractured upper first premolar was replaced by an immediate implant and a customized healing abutment designed on the perimeter of the extractive alveolus. After 3 months, the implant was restored. The facial and interdental  soft  tissue  was maintained with  appreciable  success after 5 years. The pre- and 5-year-post-treatment CT scans showed no bone loss. CONCLUSION: The use of an interim customized healing abutment helps preventing hard and soft tissues collapse.  This technique is very straightforward and might represent a smart preservation strategy when there is no indication for adjunctive hard or soft tissue grafting.

Immediate Implant and Customized Healing Abutment Promotes Tissues Regeneration: A 5-Year Clinical Report.

Significant alveolar bone resorption follows tooth extraction. Immediate implant placement alone is not sufficient to prevent this phenomenon. The present study aims at reporting the clinical and radiologic outcome of an immediate implant with a custom healing abutment. In this clinical case, a fractured upper first premolar was replaced by an immediate implant and a customized healing abutment designed on the perimeter of the extractive alveolus. After 3 months, the implant was restored. The facial and interdental soft tissue was maintained with appreciable success after 5 years. The pre-and 5-year post-treatment computerized tomography scans showed bone regeneration of the buccal plate. Use of an interim customized healing abutment helps prevent hard- and soft-tissue collapse and promotes bone regeneration. This technique is straightforward and may represent a smart preservation strategy when there is no indication for adjunctive hard or soft tissue grafting. Given the limited nature of this case report, further studies are needed to confirm the present findings.

Screening of GDM during COVID pandemic in an Italian setting: comparison between IADPSG and WHO '99 criteria.

BACKGROUND: During pandemic period, a single fast glycemia value (≥ 92 mg/dl) performed within the recommended time window for the risk level defined by the Italian guidelines, was considered an acceptable surrogate for GDM diagnosis following Italian Diabetes Association recomendations. METHODS: All pregnant women who performed an OGTT following Italian Guidelines from march 2020 to september 2021 and then delivered at our University Hospital were prospectively enrolled in this study. Primary outcome of the study was the number of women diagnosed with GDM with only the FPG value (≥ 92 mg/dl), following Italian Diabetes Societies recommendations for COVID 19 pandemic period. At the same time, the data of women who became diabetic according to the 1999 WHO criteria was collected too. The secondary outcome was the comparison of risk factors of women undergoing OGTT according to IADPSG and WHO'99 criteria for the diagnosis of GDM and associated clinical outcomes. RESULTS: The number of women with a diagnosis of GDM following Italian guidelines in the 18-month period considered was 161. Only 109 (67.7%) had a fast glucose value ≥ 92 mg/dl. No differences between IADPSG and WHO'99 groups in relation to risk factors, with the exception for overweight and obesity, and clinical outcomes. CONCLUSION: Recommendations of Italian Diabetes Societis for COVID 19 pandemic failed to recognize one third of GDM diagnosis. Clinical Trial Registration ClinicalTrials.gov, www. CLINICALTRIALS: gov , NCT05026840, August 30, 2021, 'retrospectively registered'.

Diagnosing Gestational Diabetes with a Probably Too Simplified Diagnostic Procedure Compared to International Criteria: The Indian Case Study.

Diagnostic procedures for the diagnosis of gestational diabetes mellitus (GDM) are not uniformly defined worldwide. We retrospectively applied two diagnostic procedures (i.e., the IADPSG and the Indian) to the same pregnant women in order to compare the clinical characteristics and the prevalence of risk factors for GDM. Overall, 1015 pregnant women were evaluated. GDM was diagnosed in 113 cases (11.1%) by the IADPSG criteria and in 105 cases (10.3%) by the Indian criteria. The women diagnosed with GDM according to the IADPSG criteria had higher pre-gestational BMIs, higher previous macrosomia rates, higher first trimester fasting blood glucose levels, higher fasting and 1 h glucose levels after glucose load at OGTT, and lower 2 h glucose levels at OGTT compared with the women with GDM diagnosed according to the Indian criteria. Only 49.6% of the women who were diagnosed by the IADPSG criteria were also diagnosed with GDM by the Indian diagnostic criteria. For 47.8% of the women who were diagnosed by the IADPSG criteria, a diagnosis of GDM was missed by applying the Indian diagnostic criteria. Interestingly, 49 women were diagnosed with GDM by the Indian criteria but were normal according to the IADPSG criteria. Different diagnostic criteria could lead to different GDM detection rates with different practical approaches.

The Analytical Reliability of the Oral Glucose Tolerance Test for the Diagnosis of Gestational Diabetes: An Observational, Retrospective Study in a Caucasian Population.

The Oral Glucose Tolerance Test (OGTT) is currently the gold standard reference test for the diagnosis of gestational diabetes mellitus (GDM). Several critical issues related to analytical variables have challenged its reproducibility and accuracy. This study aimed to assess the analytical reliability of the OGTT for the diagnosis of GDM. A total of 1015 pregnant women underwent a 2 h 75 g OGTT between 24 and 28 weeks of gestation. As recommended by National Academy of Clinical Biochemistry, we considered the total maximum allowable error for glucose plasma measurement as <6.9%. Assuming the possibility of analytical errors within this range for each OGTT glucose plasma value, different scenarios of GDM occurrence were estimated. GDM prevalence with standard criteria was 12.2%, and no hypothetical scenarios have shown a comparable GDM prevalence. Considering all the three OGTT values estimated at the lowest or the highest allowed value according to total maximum allowable error, GDM prevalence significantly varied (4.5% and 25.3%, respectively). Our results indicate that the OGTT is not completely accurate for GDM diagnosis.

Myoinositol plus α-lactalbumin supplementation, insulin resistance and birth outcomes in women with gestational diabetes mellitus: a randomized, controlled study.

To verify whether myo-inositol plus α-lactalbumin may reduce insulin resistance and excessive fetal growth in women with gestational diabetes mellitus. In a 12-month period, 120 women with a diagnosis of gestational diabetes mellitus were consecutively enrolled with an allocation of 1:1 in each group and randomly treated with myo-inositol plus α-lactalbumin plus folic acid (treated group) or folic acid (control group) for 2 months. Primary outcome was the variation of insulin resistance through the study evaluated by HOMA-IR. Secondary outcome was the evaluation, through the study, of fetal growth by ultrasound measurements of abdominal circumference centiles and estimated fat thickness. Some clinical outcomes were also considered. After 2 months, in the treated group, a significant reduction in insulin resistance (HOMA values 3.1 ± 1.4 vs 6.1 ± 3.4, p = 0.0002) and fetal growth was shown (Abdominal circumference centiles 54.9 ± 23.5 vs 67.5 ± 22.6, P = 0.006). Among clinical outcomes, a significant decrease in the rate of women who needed insulin (6.7% vs 20.3%, p = 0.03) and of pre-term birth (0 vs 15.2%, p = 0.007) was evidenced. A combination of myo-inositol and α-lactalbumin may reduce insulin resistance and excessive fetal growth.Clinical trial registration: ClinicalTrials.gov, http://www.clinicaltrials.gov , NCT03763669, first posted date 04/12/2018; last posted date December 06/12/2018.

Clinical Application of Easychip 8x15K Platform in 4106 Pregnancies Without Ultrasound Anomalies.

Clinical utility of Array-CGH Easychip 8x15K platform can be assessed by testing its ability to detect the occurrence of pathogenic copy number variants (CNVs), and occurrence of variants of uncertain significance (VoUS) in pregnancies without structural fetal malformations. The demand of chromosomal microarray analysis in prenatal diagnosis is progressively increasing in uneventful pregnancies. However, depending on such platform resolution, a genome-wide approach also provides a high risk of detecting VoUS and incidental finding (IF) also defined as "toxic findings." In this context, novel alternative strategies in probe design and data filtering are required to balance the detection of disease causing CNVs and the occurrence of unwanted findings. In a cohort of consecutive pregnancies without ultrasound anomalies, a total of 4106 DNA samples from cultured and uncultured amniotic fluid or chorionic villi were collected and analyzed by a previously designed Array-CGH mixed-resolution custom platform, which is able to detect pathogenic CNVs and structural imbalanced rearrangements limiting the identification of VoUS and IF. Pathogenic CNVs were identified in 88 samples (2.1%), 19 of which (0.5%) were undetectable by standard karyotype. VoUS accounted for 0.6% of cases. Our data confirm that a mixed-resolution and targeted array CGH platform, as Easychip 8x15K, yields a similar detection rate of higher resolution CMA platforms and reduces the occurrence of "toxic findings," hence making it eligible for a first-tier genetic test in pregnancies without ultrasound anomalies.

Myo-inositol supplementation to prevent gestational diabetes in overweight non-obese women: bioelectrical impedance analysis, metabolic aspects, obstetric and neonatal outcomes - a randomized and open-label, placebo-controlled clinical trial.

This study aims to evaluate the effects of myo-inositol supplementation on gestational diabetes mellitus (GDM) rates and body water distribution in overweight non-obese women. 223 overweight non-obese women pregnant were randomly assigned to the treatment group (2 g of myo-inositol plus 200 µg of folic acid) or to the placebo one (200 µg of folic acid). The treatment lasted until three weeks after delivery. A tetrapolar impedance analyser was used to study body composition. The incidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group. There was a significant increase in TBW, ECW and ICW values in the placebo group compared to the myo-inositol group. We have recorded a significant reduction in the overall incidence of pregnancy-induced hypertension in the myo-inositol group compared with the placebo group. Our results demonstrate the effectiveness of myo-inositol supplementation in preventing GDM in overweight non-obese pregnant women.

Myo-Inositol for the Prevention of Gestational Diabetes Mellitus. A Brief Review.

Gestational Diabetes Mellitus (GDM) is one of the most frequent complications of pregnancy and is characterized by a carbohydrate intolerance which is diagnosed with the oral glucose tolerance test. The prevalence of GDM in our population is about 12%, but risk factors like a previous GDM, ethnicity, a parent with diabetes mellitus type 2 and maternal overweight may increase its occurrence. Complications of GDM are a pre-term birth (before 37 wk gestation), macrosomia (birth weight ≥4 kg) and gestational hypertension. Actually, GDM is principally treated with diet and, if it is necessary, with insulin; but the challenge is the prevention of GDM. Among the measures used, changes in life-style (diet+exercise) failed to prevent GDM whereas metformin showed conflicting results. A promising supplement is myo-inositol (MI) which was given from first trimester until delivery to women at risk for GDM reporting a significant decrease in GDM occurrence by more than 60% comparing to the placebo group. Recently, a secondary analysis from 3 randomized controlled trials demonstrated that MI may also significantly reduce some of GDM complications such as pre-term birth and macrosomia with a favorable impact on mother and fetus well being.

Metabolic effects of breastfeeding in women with previous gestational diabetes diagnosed according to the IADPSG criteria.

BACKGROUND: Some studies have already investigated about the short-term favorable metabolic effects of breastfeeding in women with previous gestational diabetes mellitus (GDM). AIM: The aim of our study is to confirm whether the positive effects reported are maintained in the larger cohorts of patients with mild form of gestational diabetes mellitus (GDM) because recently diagnosed according to IADPSG criteria. MATERIALS AND METHODS: This retrospective study includes 97 evaluable consecutive women with prior GDM who have the follow-up oral glucose tolerance test at least 3 months after delivery. Fasting and 2-h plasma glucose values, homeostasis model assessment (HOMA-IR), total cholesterol, and triglycerides were obtained in pregnancy and during the post-partum control. RESULTS: These patients were divided in 81 (83.5%) who lactate until 3 months and 16 (16.5%) who did not lactate. During pregnancy, there are no significant differences between the two groups for age, BMI, fasting and 2-h plasma glucose values, HOMA-IR, total cholesterol and triglycerides. At the postpartum control, we have at univariate analysis significant differences for all these parameters except total cholesterol. After adjustment for confounders we still have, in the breastfeeding group, HOMA-IR reduction (OR 0.370; 95% CI 0.170-0.805; p < .01) as significant independent variable, whose improvement is the most acknowledged important factor for the prevention of abnormal glucose tolerance later in life. CONCLUSION: These encouraging results confirm our determination to warmly advice the women affected by GDM to breastfeeding at least for 3 months.

Gestational weight gain across continents and ethnicity: systematic review and meta-analysis of maternal and infant outcomes in more than one million women.

BACKGROUND: The association between Institute of Medicine (IOM) guidelines and pregnancy outcomes across ethnicities is uncertain. We evaluated the associations of gestational weight gain (GWG) outside 2009 IOM guidelines, with maternal and infant outcomes across the USA, western Europe and east Asia, with subgroup analyses in Asia. The aim was to explore ethnic differences in maternal prepregnancy body mass index (BMI), GWG and health outcomes across these regions. METHODS: Systematic review, meta-analysis and meta-regression of observational studies were used for the study. MEDLINE, MEDLINE In-Process, Embase and all Evidence-Based Medicine (EBM) Reviews were searched from 1999 to 2017. Studies were stratified by prepregnancy BMI category and total pregnancy GWG. Odds ratio (ORs) 95% confidence intervals (CI) applied recommended GWG within each BMI category as the reference. Primary outcomes were small for gestational age (SGA), preterm birth and large for gestational age (LGA). Secondary outcomes were macrosomia, caesarean section and gestational diabetes. RESULTS: Overall, 5874 studies were identified and 23 were included (n = 1,309,136). Prepregnancy overweight/obesity in the USA, Europe and Asia was measured at 42%, 30% and 10% respectively, with underweight 5%, 3% and 17%. GWG below guidelines in the USA, Europe and Asia was 21%, 18% and 31%, and above was 51%, 51% and 37% respectively. Applying regional BMI categories in Asia showed GWG above guidelines (51%) was similar to that in the USA and Europe. GWG below guidelines was associated with a higher risk of SGA (USA/Europe [OR 1.51; CI 1.39, 1.63]; Asia [1.63; 1.45, 1.82]) and preterm birth (USA/Europe [1.35; 1.17, 1.56]; Asia [1.06; 0.78, 1.44]) than GWG within guidelines. GWG above guidelines was associated with a higher risk of LGA (USA/Europe [1.93; 1.81, 2.06]; Asia [1.68; 1.51 , 1.87]), macrosomia (USA/Europe [1.87; 1.70, 2.06]; Asia [2.18; 1.91, 2.49]) and caesarean (USA/Europe [1.26; 1.21, 1.33]; Asia [1.37; 1.30, 1.45]). Risks remained elevated when regional BMI categories were applied for GWG recommendations. More women in Asia were categorised as having GWG below guidelines using World Health Organization (WHO) (60%) compared to regional BMI categories (16%), yet WHO BMI was not accompanied by increased risks of adverse outcomes. CONCLUSIONS: Women in the USA and western Europe have higher prepregnancy BMI and higher rates of GWG above guidelines than women in east Asia. However, when using regional BMI categories in east Asia, rates of GWG above guidelines are similar across the three continents. GWG outside guidelines is associated with adverse outcomes across all regions. If regional BMI categories are used in east Asia, IOM guidelines are applicable in the USA, western Europe and east Asia.

miRNA expression for early diagnosis of preeclampsia onset: hope or hype?

PURPOSE: Preeclampsia (PE) is a multi-systemic disease characterized by hypertension, proteinuria and other typical signs that can negatively affect the development of pregnancy. The outcome of the disease is strongly linked to the possibility of early diagnosis, in order to prevent the clinical manifestations. Pathogenesis is still unknown, although abnormalities of placenta development linked to angiogenesis alterations and abnormal trophoblastic invasion seem to be involved, corroborating the epigenetic theory. Basing on these elements, this review aims to summarize the possible role of miRNAs in PE onset, both as increased or decreased expression in placenta or as maternal serum markers. MATERIALS AND METHODS: We considered eligible all original articles (randomized, observational and retrospective studies), published between 2000 and 2016 in English language, about miRNA expression in placenta and maternal serum levels both in uncomplicated and PE pregnancies. RESULTS: Available data support a direct correlation between selective miRNAs high/low expression in placenta and maternal serum, although it is still unclear how these epigenetic changes may affect the development and outcomes of the disease. CONCLUSION: Future studies should aim to identify a robust panel of miRNA markers in order to predict the onset and development of PE.

Association of Gestational Weight Gain With Maternal and Infant Outcomes: A Systematic Review and Meta-analysis.

IMPORTANCE: Body mass index (BMI) and gestational weight gain are increasing globally. In 2009, the Institute of Medicine (IOM) provided specific recommendations regarding the ideal gestational weight gain. However, the association between gestational weight gain consistent with theIOM guidelines and pregnancy outcomes is unclear. OBJECTIVE: To perform a systematic review, meta-analysis, and metaregression to evaluate associations between gestational weight gain above or below the IOM guidelines (gain of 12.5-18 kg for underweight women [BMI <18.5]; 11.5-16 kg for normal-weight women [BMI 18.5-24.9]; 7-11 kg for overweight women [BMI 25-29.9]; and 5-9 kg for obese women [BMI ≥30]) and maternal and infant outcomes. DATA SOURCES AND STUDY SELECTION: Search of EMBASE, Evidence-Based Medicine Reviews, MEDLINE, and MEDLINE In-Process between January 1, 1999, and February 7, 2017, for observational studies stratified by prepregnancy BMI category and total gestational weight gain. DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 independent reviewers. Odds ratios (ORs) and absolute risk differences (ARDs) per live birth were calculated using a random-effects model based on a subset of studies with available data. MAIN OUTCOMES AND MEASURES: Primary outcomes were small for gestational age (SGA), preterm birth, and large for gestational age (LGA). Secondary outcomes were macrosomia, cesarean delivery, and gestational diabetes mellitus. RESULTS: Of 5354 identified studies, 23 (n = 1 309 136 women) met inclusion criteria. Gestational weight gain was below or above guidelines in 23% and 47% of pregnancies, respectively. Gestational weight gain below the recommendations was associated with higher risk of SGA (OR, 1.53 [95% CI, 1.44-1.64]; ARD, 5% [95% CI, 4%-6%]) and preterm birth (OR, 1.70 [1.32-2.20]; ARD, 5% [3%-8%]) and lower risk of LGA (OR, 0.59 [0.55-0.64]; ARD, -2% [-10% to -6%]) and macrosomia (OR, 0.60 [0.52-0.68]; ARD, -2% [-3% to -1%]); cesarean delivery showed no significant difference (OR, 0.98 [0.96-1.02]; ARD, 0% [-2% to 1%]). Gestational weight gain above the recommendations was associated with lower risk of SGA (OR, 0.66 [0.63-0.69]; ARD, -3%; [-4% to -2%]) and preterm birth (OR, 0.77 [0.69-0.86]; ARD, -2% [-2% to -1%]) and higher risk of LGA (OR, 1.85 [1.76-1.95]; ARD, 4% [2%-5%]), macrosomia (OR, 1.95 [1.79-2.11]; ARD, 6% [4%-9%]), and cesarean delivery (OR, 1.30 [1.25-1.35]; ARD, 4% [3%-6%]). Gestational diabetes mellitus could not be evaluated because of the nature of available data. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of more than 1 million pregnant women, 47% had gestational weight gain greater than IOM recommendations and 23% had gestational weight gain less than IOM recommendations. Gestational weight gain greater than or less than guideline recommendations, compared with weight gain within recommended levels, was associated with higher risk of adverse maternal and infant outcomes.

Visfatin correlates with hot flashes in postmenopausal women with metabolic syndrome: effects of genistein.

During menopause, an increased prevalence of metabolic syndrome (MetS) and central obesity seems to increase hot flashes (HFs). Visfatin is an inflammatory adipokine secreted by visceral fat. We investigated visfatin levels and its relationship with hot flash number and BMI, in postmenopausal women with MetS. We also evaluated the effect of genistein, an isoflavone effective in reducing HFs, on visfatin levels and HFs after 1 year of treatment. This was a randomized, double-blind, placebo-controlled trial. Postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein (n = 60), daily for 1 year. As main outcome measures, hot flashes number and circulating visfatin levels were evaluated. Visfatin significantly correlated with BMI and HFs number in women with MetS at basal. After 6 and 12 months, our results indicate a strong correlation and a significant effect of genistein in reducing both HFs and visfatin in women with MetS. The present study suggests that visfatin plays a role in the vasomotor symptoms, at least in postmenopausal women with metabolic syndrome. Genistein may reduce HFs decreasing the circulating levels of this inflammatory adipokine.