Fiber-type prebiotics and gynecological and breast cancers risk: the PrebiotiCa study.

Prebiotics may influence the risk of hormone-related female cancers by modulating the gut microbiota involved in estrogens metabolism. We evaluated the association of fiber-type prebiotic intake with breast, endometrial, and ovarian cancers. Data derived from a network of Italian hospital-based case-control studies (1991-2006), including 2560 cases of cancer of the breast (2588 controls), 454 of the endometrium (908 controls) and 1031 of the ovary (2411 controls). Inulin-type fructans (ITFs), and selected fructo-oligosaccharides (FOSs, nystose, kestose and 1F-ß-fructofuranosylnystose) and galacto-oligosaccharides (GOSs, raffinose and stachyose) were quantified in food products. Prebiotic intake was estimated by multiplying food frequency questionnaire intake by the foods' prebiotic content. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were derived by multiple logistic regression models. Nystose intake was marginally directly associated with breast (OR for the 4th versus the 1st quartile 1.20, 95% CI: 1.00-1.45), ovarian (OR 1.39, 95% CI: 1.04-1.84) and endometrial cancer risk (OR 1.32, 95% CI: 0.85-2.03). High 1F-ß-fructofuranosylnystose intake was inversely associated with ovarian cancer (OR 0.67, 95% CI: 0.52-0.85). ITFs, kestose, raffinose and stachyose were not associated with the three cancers. The intake of most fiber-type prebiotics was not appreciably and consistently associated with breast, endometrial and ovarian cancer risks.

Probability of second live birth after first natural and medically assisted reproduction-mediated live birth: A historical cohort study.

INTRODUCTION: Evidence on the role of medically assisted reproduction (MAR) in achieving the desired number of children is very limited. The aim of the current investigation was to assess the probability and the mode of conception of a second live birth according to the mode of conception of the first one. MATERIAL AND METHODS: This historical cohort study was based on administrative data from regional healthcare databases. Women hospitalized for childbirth in Lombardy between January 1, 2007 and December 31, 2017 were identified. The probability of a second live birth up to 2021 was estimated using the Kaplan-Meier method. We calculated this probability according to the mode of conception of the first birth, and the analysis was also performed in strata of maternal age at first birth. Cox proportional hazards models were fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the association between mode of conception at first live birth and the probability of having a second live birth. Mothers were right-censored if they moved out of the region, died, or did not have a second live birth by the end of follow-up. RESULTS: We identified 431 333 women who had their first live birth after a natural conception and 16 837 who had their first live birth after MAR. The probability of having a second live birth was 58.6% and 32.1%, respectively in the two groups (HR = 0.68, 95% CI: 0.66-0.70). Considering solely women who naturally conceived their first live birth, the probability to have a second child with MAR was 1.1% and to have a second child naturally 59.3%. The corresponding values were 11.5% and 25.2% in the group of women with a first MAR-mediated live birth. CONCLUSIONS: In our cohort, one woman out of 10 having a first MAR-mediated live birth underwent MAR programs again. Considering women who had a first natural live birth, this proportion was drastically reduced. In the field of MAR, more attention should be given to the capacity of a couple to achieve the number of desired children.

The relationship between treatment integrity and outcome in group psychotherapy: A systematic review.

Treatment integrity is defined as the extent to which the treatment has been implemented according to a specific theoretical model. It consists of two components: adherence, that is, the degree to which the therapist implements the techniques prescribed by the theoretical model, and competence, that is, the degree to which the therapist skilfully and appropriately implements the techniques prescribed by the model. Recently, the issue of integrity is gaining increasing importance in psychotherapy research, especially in an attempt to clarify its role in influencing the effectiveness of treatments. However, most studies focus on the individual setting. Therefore, this systematic review aims at investigating the relationship between integrity and outcome in group clinical treatments. Results highlighted a positive relationship between group treatment integrity and outcome. Moreover, this review provided insights for implications for research, clinical practice, and training of therapists, identifying questions that still need to be answered and tracing possible future research directions.

Physiological synchronization and innovative moments in psychotherapy: A single-case study of micro-process.

OBJECTIVE: Interpersonal synchronization is increasingly studied as a biomarker of empathy, therapeutic alliance, and treatment outcome. However, most studies average data over sessions, leaving associations between synchrony and actual interactions largely unexplored. We aim to showcase a novel approach examining synchronization during specific micro-processes: Innovative Moments (IM) as markers of exceptions to clients' problematic patterns of meaning. METHODS: Electrodermal activity was recorded over 15 sessions of a psychodynamic psychotherapy single case. Moment-to-moment patient-therapist synchrony was calculated using the Adaptive Matching Interpolated Correlations (AMICo) algorithm. The Innovative Moments Coding System was utilized to identify IMs within session transcripts with precise timing. Monte-Carlo permutation tests were conducted to examine the association between physiological synchrony and IM Levels of increasing complexity (Levels 1-3). RESULTS: Higher-than-random synchronization emerged during Level 3 IMs (p = 0.046; d = 0.21) but not in lower Levels. Post-hoc qualitative analyses linked high synchrony to sub-processes of Level 3 IMs, such as positive contrasts and attributions for change. CONCLUSION: Our findings show it is possible to link moment-by-moment physiological co-regulation to theoretically identified meaning-making processes. While generalization of these observations is undue, this work demonstrates a robust and promising application of a multimodal approach to investigating psychotherapy, providing insights into both the clinical case and the theoretical model adopted.

Diabetes risk reduction diet and ovarian cancer risk: an Italian case-control study.

PURPOSE: To investigate the relation between a diabetes risk reduction diet (DRRD) and ovarian cancer. METHODS: We used data from a multicentric case-control study conducted in Italy, including 1031 incident ovarian cancer cases and 2411 controls admitted to hospital centres for acute non-malignant disease. Subjects' diet prior to hospital admission was collected using a validated food frequency questionnaire. Adherence to the DRRD was measured using a score based on 8 dietary components, giving higher scores for greater intakes of cereal fiber, coffee, fruit, nuts, higher polyunsaturated to saturated fatty acids ratio, lower glycemic index of diet, and lower intakes of red/processed meat, and sweetened beverages/and fruit juices. Higher scores indicated greater adherence to the DRRD. Multiple logistic regression models were fitted to calculate the odds ratios (OR) of ovarian cancer and the corresponding 95% confidence intervals (CI) for approximate quartiles of the DRRD score. RESULTS: The DRRD score was inversely related to ovarian cancer, with an OR of 0.76 (95%CI: 0.60-0.95) for the highest versus the lowest quartile of the score (p for trend = 0.022). The exclusion of women with diabetes did not change the results (OR = 0.75, 95%CI: 0.59-0.95). Inverse associations were observed in strata of age, education, parity, menopausal status, and family history of ovarian/breast cancer. CONCLUSION: Higher adherence to a diet aimed at reducing the risk of diabetes was inversely associated with ovarian cancer. Further evidence from prospective investigations will be useful to support our findings.

ART and the forgotten siblings: a call for research.

A broader definition of infertility is the incapacity to have the intended number of children. However, most literature on ART exclusively focuses on live birth as an outcome, rather than on the capacity to fully realize the reproductive wishes of the couples. This issue has probably received scant attention because the total fertility rate is below replacement levels in affluent countries, and one may simplistically assume that only a minority of couples may be interested in more than one child. This assumption, however, is unproven and presumably erroneous. Unfortunately, evidence on the rate of return in couples who conceived their first child with ART is scant and information on the intended number of children in infertile couples is lacking. In general, we plea for more research on this subject. The documentation of an intended number of children above two and a high return rate in infertile couples may lead to changes in clinical practice, such as the storage of oocytes or embryos prior to initiating embryo transfers. This could improve the chance of conceiving the second child when the couple comes back some years later. In addition, the identification of the determinants for non-return as well as those explaining the gap between the intended and the realized number of children may reveal specific barriers and possibly how to tackle them. However, at present, available evidence is insufficient to advocate any intervention. Thorough research is warranted.

Prevalence and Factors Associated With Intertwin Birth Weight Discordance Among Same-Sex Twins in Lombardy, Northern Italy.

This population-based cohort study investigated the prevalence, potential risk factors, and consequences of birth weight discordance (BWD) among same-sex twins. We retrieved data from the automated system of healthcare utilization databases of Lombardy Region, Northern Italy (2007-2021). BWD was defined as 30% or more disparity in birth weights between the larger and the smaller twin. Multivariate logistic regression was used to analyze the risk factors of BWD in deliveries with same-sex twins. In addition, the distribution of several neonatal outcomes was assessed overall and according to BWD level (i.e., ≤20%, 21-29, and ≥30%). Finally, a stratified analysis by BWD was performed to assess the relationship between assisted reproductive technologies (ART) and neonatal outcomes. We identified 11,096 same-sex twin deliveries; 556 (5.0%) pairs of twins were affected by BWD. Multivariate logistic regression analysis showed that maternal age ≥35 years (OR 1.26, 95% CI [1.05,5.51]), low level of education (OR 1.34, 95% CI [1.05, 1.70]), and ART (OR 1.16, 95% CI [0.94, 1.44], almost significant due to the low power) were independent risk factors for BWD in same-sex twins. Conversely, parity (OR 0.73, 95% CI [0.60, 0.89]) was inversely related. All the adverse outcomes observed were more common among BWD pairs than non-BWD ones. Instead, a protective effect of ART was observed for most neonatal outcomes considered among BWD twins. Our results suggest that conception after ART increases the risk of developing a high disparity between the weights of the two twins. However, the presence of BWD may complicate twin pregnancies, compromising neonatal outcomes, regardless of the modality of conception.

Spontaneous and induced abortions in women with a diagnosis of gestational related neoplasm: a population-based linkage study in Lombardy, 2010-2020.

BACKGROUND: A diagnosis of cancer during pregnancy or within one year after the end of pregnancy is a major clinical and public health issue. The current study aimed at estimating the incidence of pregnancy-associated cancer (PAC) and assessing whether the risk of abortion is increased in women diagnosed with cancer. METHODS: This population-based cohort study used the regional healthcare utilization (HCU) databases of Lombardy, the largest region in Italy, to identify the women who delivered between 2010 and 2020. PAC were identified by oncological ICD-9-CM codes reported in the hospital discharge forms. We computed the ratio of PAC cases to the total number of pregnancies. Following a diagnosis of PAC, the prevalence ratio (PR) of abortion and the corresponding 95% confidence interval (CI), was estimated using a log-binomial model adjusted for maternal age. RESULTS: During the study period, 926 women who gave birth (1.29 cases per 1000 births) and 341 women who had an abortion (1.52 cases per 1000 abortions) were diagnosed with PAC. Regardless of the outcome of pregnancy, the risk of PAC increased with increasing age. The rate of PAC was initially lower among births, but it came very close to the rate of PAC among abortions in the last two calendar years. The proportion of abortions among women with PAC gradually decreased from 27.7% in 2010-2012 to 18.5% in 2019-2020 (p-value < 0.001). Overall, a diagnosis of PAC was related to an approximately 10% increased risk of abortion (PR = 1.11, 95%CI:1.01-1.22). However, no association was observed in 2019-2020 (PR = 0.87, 95%CI:0.65-1.17). Considering only diagnoses made during the first trimester of pregnancy, the risk of abortion was about 2.5 times higher (PR = 2.53, 95%CI:2.05-3.11) and the risk of induced abortion was almost 4 times higher (PR = 3.71, 95%CI:2.82-4.90). CONCLUSION: In this population the risk of abortion was about 10% higher in women with PAC than in women without PAC. However, this association tended to decrease in more recent calendar periods. This trend seemed to be influenced more by spontaneous than by induced abortions.

Trends in the incidence of major birth defects after assisted reproductive technologies in Lombardy Region, Northern Italy.

PURPOSE: The incidence of birth defects is increased in children born after assisted reproductive technologies (ART). However, changes in ART over time could influence this incidence. To investigate this issue, we present the frequency and trends of birth defects in ART and natural pregnancies in Lombardy, Northern Italy, during the period 2014-2020. METHODS: This is a population-based study using automated system of healthcare utilization (HCU) databases. ART pregnancies included only those obtained with conventional IVF or ICSI. After identifying the total number of deliveries, the rate of newborns with birth defects was compared between natural and ART pregnancies. A logistic regression model was used to calculate the adjusted odd ratio (OR). Analyses were repeated for every calendar year. RESULTS: Overall, 508,421 deliveries were identified, of which 14,067 (2.8%) were achieved after IVF-ICSI. A decreasing trend in birth defects over time was highlighted. The adjusted OR dropped from 1.40 (95%CI: 1.03-1.91) in 2014 to 0.92 (95%CI: 0.69-1.22) in 2020. During the study period, a significant reduction in multiple pregnancy and in the ratio of ICSI to conventional IVF was also observed, explaining at least in part the positive trend observed for birth defects. CONCLUSION: The increased risk of birth defects in children born after IVF-ICSI is not steady over time. A decline of this risk emerged in our region. Policy changes in ART may explain this beneficial effect.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and endometrial cancer risk: a multicentric case-control study.

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) published evidence-based recommendations for cancer prevention focusing on body weight, physical activity, and diet. Our aim is to evaluate whether adherence to the WCRF/AICR recommendations could reduce endometrial cancer risk. We used data from a multicentric, Italian hospital-based case-control study (1992-2006) including 454 endometrial cancer cases and 908 age-matched controls. Adherence to the WCRF/AICR recommendations was measured using a score (range: 0-7) based on seven components: body mass index (BMI), physical activity and five dietary items; higher scores indicated higher adherence. Odds ratios (OR) were estimated by multiple (adjusted) conditional logistic regression models including terms for major confounders and energy intake. Adherence to the WCRF/AICR recommendations was inversely related to endometrial cancer risk (OR = 0·42, 95 % confidence interval (CI) 0·30, 0·61 for the highest compared with the lowest score quartile), with a significant trend of decreasing risk with increasing adherence. An inverse association was also observed for a score including only dietary recommendations (OR = 0·67, 95 % CI 0·46, 0·96 for the highest compared with the lowest score tertile). In stratified analyses, the association was stronger among women with a normal weight, those who were older, and consequently those in post-menopause, and those with ≥ 2 children. In conclusion, high adherence to the WCRF/AICR recommendations has a favourable role in endometrial cancer risk, which is not fully explained by body weight.

The role of maternal age on the risk of preterm birth among singletons and multiples: a retrospective cohort study in Lombardy, Norther Italy.

BACKGROUND: All over the world, especially in the developed countries, maternal age at birth is rising. This study aimed to assess the role of maternal age on the occurrence of preterm birth (PTB) in a large birth cohort of Lombardy Region, Northern Italy. METHODS: This population-based study used data from regional healthcare utilization databases of Lombardy to identify women who delivered between 2007 and 2017. PTBs were defined as births before 37 completed weeks of gestation and considered according to the gestational age (two categories: < 32 weeks and 32 to 36 weeks). Six maternal age groups were defined (< 20, 20-24, 25-29, 30-34, 35-39, ≥40 years). Logistic regression models were fitted to estimate the crude and adjusted odds ratio (aOR) and the corresponding 95% confidence interval (CI) for PTB among different maternal age groups. Analyses were separately performed according to type of pregnancy (singletons and multiples). Reference group was the age group with the lowest frequency of PTB. RESULTS: Overall, 49,759 (6.6%) PTBs were observed, of which 41,807 were singletons and 7952 were multiples. Rates of PTB were lowest in the women aged 25-29 years among singletons and in the 30-34 years old group among multiples. Our results described a U-shaped association between maternal age and risk of PTB. In particular, the risk of a singleton PTB between 32 and 36 weeks was significantly higher for women aged less than 20 years (aOR = 1.16, CI 95%: 1.04-1.30) and more than 40 years (aOR = 1.62 CI 95%: 1.54-1.70). The highest risk of a multiple delivery between 32 and 36 weeks was observed among women aged less than 25 years and more than 40 years (aOR = 1.79, CI 95%: 1.01-3.17, aOR = 1.47, CI 95%: 1.16-1.85 and aOR = 1.36, CI 95%: 1.19-1.55 respectively for < 20, 20-24 and > 40 age categories). PTB before 32 completed weeks occurred more frequently in the same age categories, except that among multiples no association with advanced maternal age emerged. CONCLUSION: Our study suggested that, after adjustment for potential confounders, both advance and young maternal age were associated with an increased risk of PTB.

Acute myocarditis: prognostic role of speckle tracking echocardiography and comparison with cardiac magnetic resonance features.

To evaluate longitudinal systolic function in patients with myocarditis, its correlation with cardiac magnetic resonance (CMR) features, and its predictive value in functional recovery and arrhythmias onset during follow-up (FU) on optimized medical therapy (OMT). Patients with acute myocarditis, confirmed through CMR criteria, and age- and sex-matched healthy controls were enrolled. Two-dimensional (2D) transthoracic echocardiography, including speckle tracking analysis, was performed at admission and after 6 months of FU. Patients of myocarditis group also underwent 24 h ECG Holter monitoring during FU. 115 patients with myocarditis (mean age 41 ± 17, 70% males) and 70 healthy subjects were enrolled. Global longitudinal strain (GLS) and sub-epicardial strain were markedly lower in the myocarditis group than in controls (mean GLS%: - 14.1 ± 5.1 vs - 23.1 ± 3.6, p < 0.001). A strong positive correlation between total scar burden (TSB) on CMR and baseline LV GLS was found (r = 0.67, p < 0.0001). GLS improved after 6 months of FU in myocarditis on OMT (mean GLS%: - 14.1 ± 5.1 vs - 16.5 ± 4.8, p < 0.01). By bivariate correlation analysis, baseline LVEF, GLS, and TSB were all associated with LVEF at 6 months of FU. Moreover, by multivariable linear regression analysis, these parameters confirmed to be independent predictors of functional recovery at 6 months (LVEF ß 0.38, p < 0.01; GLS ß - 0.35, p < 0.01; total scar burden ß - 0.52, p < 0.0001). Segmental peak systolic strain was significantly different between segments with and without late gadolinium enhancement on CMR (- 13.2 ± 3.1% vs - 18.1 ± 3.5%, p < 0.001). A segmental strain of - 12% identified scar with a sensitivity of 79% and a specificity of 84% (AUC = 0.91; 95% CI 0.73-0.97; p < 0.001). In addition, baseline LV GLS in myocarditis resulted predictive of non-sustained ventricular tachycardias (cut-off value > - 12%; sensitivity84%; specificity74.4%; AUC = 0.75). Parameters of myocardial longitudinal deformation are importantly associated with the presence of a scar on CMR and are predictors of functional outcome and ventricular arrhythmias in patients with acute myocarditis. Their assessment during ultrasound examination should be considered to get more information about the prognosis and risk stratification of this subset of patients.

Trends in Dizygotic and Monozygotic Spontaneous Twin Births During the Period 2007-2017 in Lombardy, Northern Italy: A Population-Based Study.

In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007-2017. This is a population-based study using the regional healthcare utilization databases of the Lombardy Region. The total number of spontaneous twin deliveries, in separate strata of like and unlike sex, was obtained. Moreover, estimates of DZ and MZ twin births were calculated using Weinberg's method. The standardized rates (SRs), adjusted for maternal age, of DZ and MZ twin births were computed according to calendar period. The twinning rates were calculated among strata of parity and maternal age. Finally, DZ:MZ ratio was calculated. Among the 734,278 spontaneous deliveries, 9176 (12.5 out of 1000 births) couples of twins were identified. In the three periods considered (i.e. 2007-2010, 2011-2014 and 2015-2017), no trend in the SRs of MZ twins was observed, respectively 0.41 (95% CI [0.40, 0.43]), 0.43 (95% CI [0.42, 0.45]) and 0.43 (95% CI[0.42, 0.45]). Differently, a slightly decreasing trend was observed in DZ twins SRs, respectively 0.87 (95% CI [0.84, 0.89]), 0.81 (95% CI [0.79, 0.83]), and 0.78 (95% CI [0.76, 0.80]). As concerns parity and maternal age, the rate of DZ twin births was consistently higher in nulliparae women aged 35 years or more. In our cohort, despite the increase of maternal age, a decline of spontaneous twin births emerged, especially due to the downward trend of DZ twins.

Fatty acids intake and outcomes of assisted reproduction in women referring to an Italian Fertility Service: cross-sectional analysis of a prospective cohort study.

BACKGROUND: Infertility affects 15% of couples in Italy and approximately 10%-12% of couples worldwide. Focusing on female fertility, there are multiple causes, among which diet has a great influence. METHODS: We investigated whether the consumption of certain fatty acids affects four outcomes of the assisted reproduction techniques. From September 2014 to December 2016, women referring to our Italian fertility unit, eligible for assisted reproduction techniques, were invited to participate. Information on diet was recorded through a validated food frequency questionnaire. RESULTS: Four hundred and ninety-four women were included, of whom 95% achieved good quality oocytes, 87% achieved embryo transfer, 32.0% achieved clinical pregnancies and 24.5% achieved pregnancy at term. The fourth quartile of saturated fatty acids consumption, compared to the first one, showed an association with clinical pregnancy (adjusted relative risk 0.67, 95% confidence interval 0.45-1.00, p = 0.0491). Some associations emerge accounting for confounders. Age was associated with clinical pregnancy and pregnancy at term in the models considering all fatty intakes and food groups variables but was not associated with oocytes quality and embryo transfer. Physical activity was associated with clinical pregnancy. CONCLUSIONS: There is biological plausibility for the effect of omega-3 and omega-6 polyunsaturated fatty acids on oocyte development via synthesis of eicosanoids, even if only limited associations are shown in the present study. Future research should aim to measure the serum levels of fatty acids and investigate the outcomes of assisted reproduction techniques.

The role of emotion regulation and intolerance to uncertainty on the relationship between fear of COVID-19 and distress.

The COVID-19 pandemic is increasing negative consequences on mental health around the globe. To date, research on what psychological factors could influence individuals' distress is still scarce. The current study aims to test a multiple mediation model to examine the role of Intolerance of Uncertainty (IU) and emotional regulation (i.e., expressive suppression and cognitive reappraisal) as joint factors, which can increase understanding of psychological distress due to the COVID-19 outbreak. An online survey measuring fear of COVID-19, IU, emotional regulation, and psychological distress was administered to 3863 Italian adults (females 73.3%; M age = 36.44; SD = 14.74) during lockdown. Results showed that IU partially mediated the effect of fear of COVID-19 on depression, anxiety and stress. Moreover, individuals with difficulties in managing the uncertainties due to their fear of COVID-19 may be at risk for heightened use of expressive suppression and depression. However, individuals with both higher IU and expressive suppression showed lower level of stress. High cognitive reappraisal has a mediational effect on the relationship between fear of COVID-19, IU, and lower psychological distress. Findings suggest that IU and emotional regulation should be targeted for informing the development of tailored treatments to reduce the negative consequences of the outbreak. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03071-5.

Development of a screening method to rapidly discriminate extravirgin olive oil from other edible vegetable oil by means of direct sample analysis with high resolution mass spectrometry.

Extra virgin olive oil is the highest quality olive oil mainly due to its beneficial constituents and nutritional properties. However, olive oil adulteration is a common fraudulent practice by deliberate mislabelling of less expensive oil categories and admixing expensive olive oils with low oils. To protect consumers from such commercial frauds, an easy and fast method to detect the real composition of oil is needed. For this study we used direct sampling analysis (DSA) coupled with a high-resolution mass spectrometer (AxION2 TOF Perkin Elmer) to analyse the fatty acid composition of three types of edible oil: extra virgin olive oil, refined olive oil and seed oil (EVOO, ROO, and SO respectively) to find a marker that could distinguish between them. Good precision in repeatability and reproducibility (RSD% < 15%) was obtained. The fatty acid ratio between the oleic acid/oleic acid dimer was able to distinguish EVOO from the other two types of oil, while the ratio between linoleic and oleic acid was found to discriminate refined oil from seed oil. The development of an easy, fast and cost-effective method can help to limit commercial frauds, increase the number of controlled samples, and enhance food control along the commercial chain. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05063-y.

Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of 6 randomized trials.

BACKGROUND: Chemotherapy-induced neutropenia (CIN) has been demonstrated to be a prognostic factor in several cancer conditions. We previously found a significant prognostic value of CIN on overall survival (OS), in a pooled dataset of patients with advanced non-small-cell lung cancer (NSCLC) receiving first line chemotherapy from 1996 to 2001. However, the prognostic role of CIN in NSCLC is still debated. METHODS: We performed a post hoc analysis pooling data prospectively collected in six randomized phase 3 trials in NSCLC conducted from 2002 to 2016. Patients who never started chemotherapy and those for whom toxicity data were missing were excluded. Neutropenia was categorized on the basis of worst grade during chemotherapy: absent (grade 0), mild (grade 1-2), or severe (grade 3-4). The primary endpoint was OS. Multivariable Cox model was applied for statistical analyses. In the primary analysis, a minimum time (landmark) at 180 days from randomization was applied in order to minimize the time-dependent bias. RESULTS: Overall, 1529 patients, who received chemotherapy, were eligible; 572 of them (who received 6 cycles of treatment) represented the landmark population. Severe CIN was reported in 143 (25.0%) patients and mild CIN in 135 (23.6%). At multivariable OS analysis, CIN was significantly predictive of prognosis although its prognostic value was entirely driven by severe CIN (hazard ratio [HR] of death 0.71; 95%CI: 0.53-0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92-1.58). Consistent results were observed in the out-of-landmark group (including 957 patients), where both severe and mild CIN were significantly associated with a reduced risk of death. CONCLUSION: The pooled analysis of six large trials of NSCLC treatment shows that CIN occurrence is significantly associated with a longer overall survival, particularly in patients developing severe CIN, confirming our previous findings.

Effects of the early phase of the COVID-19 pandemic on natural and ART-mediated birth rates in Lombardy Region, Northern Italy.

RESEARCH QUESTION: What effects did the early phase of the COVID-19 pandemic have on natural and assisted reproductive technology (ART)-mediated birth rates? DESIGN: Regional registries were consulted with permission from the Health Authorities of Lombardy Region, Northern Italy, an area particularly affected by the early phase of the epidemic. Deliveries occurring in the area between 1 January 2019 and 31 December 2020 from women beneficiaries of the National Health System and resident in Lombardy were identified. Comparisons mainly focused on December 2020, when women who conceived after 8 March (the start of the stringent lockdown imposed by the authorities) were expected to deliver. RESULTS: When comparing the periods January to November in 2019 and 2020, a 5.1% reduction of monthly general birth rate (from 5732 in 2019 to 5438 in 2020) was observed. The contribution of ART births was similar in 2019 and 2020, being 4.4% and 4.5%, respectively. In December 2020, a notable drop in natural (-17.8%), ART-mediated (-86.6%) and overall (-21.0%) births was observed compared with December 2019. After adjusting for the expected 5.1% reduction, the inferred effect of the COVID-19 crisis corresponded to a 16.7% reduction in birth rate, of which 76% was related to natural (707 births) and 24% to ART (218 births) conceptions. CONCLUSIONS: This is the first study providing population-based evidence on the effects of COVID-19 and its related stringent restrictions on birth rates. The birth rate was dramatically reduced following the critical period, and the closure of ART centres played only a marginal role (24%) in the overall detrimental effect.

Obstetric and neonatal outcomes in women with pregnancy associated cancer: a population-based study in Lombardy, Northern Italy.

BACKGROUND: Pregnancy associated cancer (PAC) may lead to adverse obstetric and neonatal outcomes. This study aims to assess the association between PACs and adverse perinatal outcomes [i.e. labor induction, iatrogenic delivery, preterm birth, small for gestational age (SGA) newborn, low Apgar score, major malformations, perinatal mortality] in Lombardy, Northern Italy. METHODS: This population-based historic cohort study used the certificate of delivery assistance and the regional healthcare utilization databases of Lombardy Region to identify beneficiaries of National Health Service who delivered between 2008 and 2017. PACs were defined through oncological ICD-9-CM codes reported in the hospital discharge forms. Each woman with PAC was matched to four women randomly selected from those cancer-free (1:4). Log-binomial regression models were fitted to estimate crude and adjusted prevalence ratio (aPR) and the corresponding 95% confidence interval (CI) of each perinatal outcome among PAC and cancer-free women. RESULTS: Out of the 657,968 deliveries, 831 PACs were identified (1.26 per 1000). PAC diagnosed during pregnancy was positively associated with labor induction or planned delivery (aPR=1.80, 95% CI: 1.57-2.07), cesarean section (aPR=1.78, 95% CI: 1.49-2.11) and premature birth (aPR=6.34, 95% CI: 4.59-8.75). No association with obstetric outcomes was found among PAC diagnosed in the post-pregnancy. No association of PAC, neither during pregnancy nor in post-pregnancy was found for SGA (aPR=0.71, 95% CI: 0.36-1.35 and aPR=1.04, 95% CI: 0.78-1.39, respectively), but newborn among PAC women had a lower birth weight (p-value< 0.001). Newborns of women with PAC diagnosed during pregnancy had a higher risk of borderline significance of a low Apgar score (aPR=2.65, 95% CI: 0.96-7.33) as compared to cancer-free women. CONCLUSION: PAC, especially when diagnosed during pregnancy, is associated with iatrogenic preterm delivery, compromising some neonatal heath indicators.

Trend of medically induced monozygotic twin deliveries according to age, parity, and type of assisted reproductive technique during the period 2007-2017 in Lombardy Region, Northern Italy: a population-based study.

PURPOSE: The risk of monozygotic (MZT) twinning is increased in pregnancies after assisted reproductive technologies (ART). However, determinants remain poorly understood. To shed more light on this issue, we analyzed the estimated frequency of MZT twins from ART in Lombardy, Northern Italy, during the period 2007-2017. METHODS: This is a population-based study using regional healthcare databases of Lombardy Region. After having detected the total number of deliveries of sex-concordant and sex-discordant twins from ART, we calculated MZT rate using Weinberg's method. Standardized ratios (SRs) and corresponding 95% confidence intervals (CI) of MZT deliveries, adjusted for maternal age, were computed according to calendar period, parity, and type of ART. RESULTS: On the whole, 19,130 deliveries from ART were identified, of which 3,446 were twins. The estimated rate of MZT births among ART pregnancies was higher but decreased over time (p-value = 0.03); the SRs being 1.33 (95% CI: 1.18-1.51), 0.96 (95% CI: 0.83-1.11), and 0.92 (95% CI: 0.79-1.07) for the periods 2007-2010, 2011-2014, and 2015-2017, respectively. The SRs of MZT among women undergoing first-level techniques, conventional in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) were 0.47 (95% CI: 0.38-0.57), 1.02 (95% CI: 0.88-1.17), and 1.43 (95% CI: 1.27-1.61) (p-value < 0.0001). The ratio of MZT births was significantly higher in women younger than 35 years (p-value < 0.0001) and slightly higher among nulliparae (p-value < 0.0001). CONCLUSION: Despite a reduction of MZT rate from ART over the time, the risk remains higher among ART pregnancies rather than natural ones. Younger women and women undergoing ICSI showed the highest risk of all.