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Objective: To evaluate the impact of adjuvant chemotherapy, type of ovarian surgery, and the surgical approach on fertility in patients with stage I immature teratoma of the ovary., Methods: Clinicopathologic data were retrospectively collected and analyzed from a cohort of 47 patients with childbearing desire treated for a stage I immature teratoma of the ovary at IRCCS San Gerardo dei Tintori Hospital, Monza, Italy. Multivariate logistic regression was used to address the influence of chemotherapy and type of surgery on the outcome., Results: Among the patients included, 78.7% (37/47) were able to get pregnant, with a live birth rate of 80.9% (51/63 pregnancies). These rates were not different between adjuvant chemotherapy versus surveillance group (62.5% (5/8) and 82.0% (32/39), respectively; p=0.22) nor between the type of ovarian surgery (cystectomy vs unilateral salpingo-oophorectomy; p=0.57) and surgical approach (laparotomy or laparoscopy; p=0.18). A statistically significant difference was found for stage of disease (a decrease in pregnancy rate from 86.5% (32/37) for stage IA to 50.0% for stage IC (5/10); p=0.02), but it was not confirmed in the multivariate analysis. After relapse diagnosis and management, a total of 62.5% (5/8) of patients conceived and had at least one live birth baby., Conclusions: The fertility-sparing approach is feasible in this population, and fertility does not depend on surgical approach or post-operative treatment. However, adjuvant chemotherapy should be carefully evaluated in this setting., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The standard surgical treatment of advanced ovarian carcinoma is primary debulking surgery (PDS) aiming to complete cytoreduction. The need to achieve complete cytoreduction has shifted the surgical paradigm to more complex procedures, whose impact on morbidity is controversial. The objective of this retrospective analysis is to explore the impact of extensive PDS on morbidity and oncologic outcomes in a real-world scenario., Methods: A retrospective single-center analysis was performed on 137 patients with advanced high-grade ovarian carcinoma (HGOC) who received PDS in 2015-2020. Patients treated in 2015-2017 (Group 1) were compared to patients treated in 2018-2020 (Group 2). The two periods were chosen according to the higher complexity of surgical procedures introduced in 2018., Results: The increase in complete cytoreduction observed in Group2 (RD 0: 33 % vs 61 %, p = 0,008) was related to a higher surgical complexity (Aletti Score: 4 vs 6, p = 0,003) and did not reflect an increase in peri-operative complications (CCI: 20,9 vs 20,9, p = 0,11). After a median FUP of 44 months, PFS and OS at 24 months were 33,60 % vs 47,33 % (p = 0,288) and 72,10 % vs 80,37 % (p = 0,022) in Group 1 and 2, respectively., Conclusions: An extensive surgical effort leads to a significant increase in complete cytoreduction with acceptable morbidity. Arm-in-arm with novel maintenance therapies, it contributes to increasing the outcomes of patients with advanced HGOC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Multidrug-resistant organisms (MDROs) are prevalent in patients admitted to the Emergency Department (ED) and increase the risk of inappropriate empirical antibiotic therapy. Risk stratification for MDRO infection is essential to early identify patients requiring empirical broad-spectrum antibiotic therapy, but it remains challenging for emergency physicians. This study aimed to evaluate prevalence, risk factors, and outcomes of patients admitted to the ED with a bloodstream infection (BSI) caused by MDROs. A retrospective observational study enrolling all consecutive adult patients admitted with a BSI to the ED of Niguarda Hospital, Italy, from January 2019 to December 2021 was performed. 757 patients were enrolled, 14.1% with septic shock. 156 (20%) patients had a BSI caused by MDRO: extended-spectrum beta-lactamase (ESBL) producing Enterobacterales were the most prevalent followed by methicillin-resistant Staphylococcus aureus (MRSA). Risk factors for BSI due to MDRO and specifically for ESBL were chronic renal failure (OR 2.2; 95%CI 1.4-3.6), nursing home residency (OR 4.4; 95%CI 1.9-10.2) and antibiotic therapy in the last 90-days (OR 2.6; 95%CI 1.7-4), whereas for MRSA were dialysis (OR 12.3; 95%CI 1.8-83), antibiotic therapy and/or hospital admission in the past 90-days (OR 3.6; 95%CI 1.2-10.6) and ureteral stent or nephrostomy (OR 7.8; 95%CI 1.5-40.9). Patients with BSI due to MDRO had a higher rate of inappropriate empirical antibiotic therapy (50%) and longer length of stay, but no higher in-hospital mortality. Among patients admitted to the ED with a BSI, MDROs are frequent and often associated with inappropriate empirical antibiotic therapy. Specific updated risk factors for MDRO may help clinicians to better identify patients requiring a broader antibiotic therapy in the ED, while awaiting microbiological results., (© 2024. The Author(s).)

The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged <70 years, high BMI was associated with an increased risk of MACE, whereas among the older subjects it was associated with lower risk. Compared to the group with normal weight/healthy metabolic status, the metabolically healthy participants aged <70 years who were overweight/obese had an increased risk of MACE with an adjusted hazard ratio of 3.81 (95% CI, 1.34-10.85, p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07-6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27], p < 0.001 and HR 1.25 [1.09-1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

Background: Few certainties exist regarding optimal management of Blood Pressure (BP) in the very first hours after an ischemic stroke and many questions remain still unanswered. Our work aimed to evaluate the role of BP and its trend as possible determinants of in-hospital mortality (primary outcome), discharge disabilities and hospitalization length (secondary outcomes) in ischemic stroke patients presented with Hypertensive Emergencies (HE)., Methods: We retrospectively evaluated patients presented to Niguarda Hospital, Emergency Department (ED), from 2015 to 2017 with a neurological ischemic HE. BP at ED presentation (T0), its management in ED (T1) and its values at the stroke unit admission (T2) were evaluated., Results: 267 patients were included (0.13 % of all ED accesses and 17.9 % of all ischemic strokes). In the whole population, BP values were not associated with in-hospital mortality while T0 and T2 SBP result were associated to discharge disability and hospitalization length. In pre-specified subgroup analysis these associations were confirmed only in untreated subjects (not anti-hypertensive nor thrombolysis). In fact, no significant relationship can be found between BP values and any secondary outcome in thrombolysis and anti-hypertensive treated patients., Conclusions: BP values and its management can not be related to in-hospital mortality in stroke patients, presented with HE, while they are associated to discharge disability and hospitalization length. In subgroup analysis, results were confirmed only in untreated (not anti-hypertensive therapies nor thrombolytic)., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied ( n = 2230). The risk of CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

Purpose: Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk., Methods: The analysis included 16,649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis., Results: During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality, than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only one of the two factors., Conclusions: The results of this study indicate that these TyG (a low-cost and simple non-invasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort., Methods and Results: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P <0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P =0.004) and 1.150 (95% CI, 1.021-1.295, P =0.02), respectively., Conclusions: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Introduction: The study of the macroscopic appearance of the placenta may represent a useful tool to understand the pathophysiology of adverse pregnancy outcomes. The aim of this study was to evaluate biometry and morphology of placentas in relation to maternal, neonatal and pregnancy course characteristics., Methods: Clinical and placental data (biometry and macroscopic features of chorionic disk and adnexa) from unselected consecutive singleton pregnancies were recorded at the same Institution. Placental efficiency was approximated as ratio between fetal and placental weight (FPR). The total population was grouped according to the presence of any maternal comorbidity or pregnancy complication (group 1), neonatal complications diagnosed only at birth (2) and absence of any comorbidity (3). Multi-adjusted general linear and logistic regression models were performed to analyze associations between groups and placental biometry and morphology., Results: The study population counted 1008 pregnancies: 576 (57.2 %) classified as group 1, 76 (7.5 %) as group 2 and 356 (35.3 %) uncomplicated controls (group 3). In multivariate models adjusted for confounding factors, no significant differences in placental biometry and macroscopic features were observed among the three groups. Maternal BMI was significantly associated with higher placental and birth weight and lower FPR; moreover FPR was significantly higher in pregnancies carrying males compared to female neonates., Discussion: Maternal comorbidity or pregnancy disease was not associated with significant changes in placental macroscopic biometry and morphology. Conversely, maternal pregestational BMI and fetal sex impact on placental biometry and efficiency, suggesting different intrauterine adaptations in obese mothers and in male and female fetuses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Università degli Studi di Milano. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Hyperuricemia (HU) has been shown to be associated with an adverse impact on cardiovascular and metabolic risk. Scanty data are available in the general population on the longitudinal changes in serum uric acid (SUA), the occurrence of HU and their potential predictors. We examined during a 25-year follow-up the SUA changes and the factors associated with HU development in the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study., Methods and Results: We analyzed data collected in 561 subjects of the PAMELA study evaluated during an average follow-up time amounting to 25.4 ± 1.0 years (mean ± SD). HU was defined by the Uric Acid Right for Heart Health (URRAh) cutoff (5.1 for females and 5.6 mg/dl for males). Mean SUA values during follow-up increased from 4.7 ± 1.1 to 5.0 ± 1.2 mg/dl (P<0.001), the average SUA elevation amounting to of 0.3 ± 1.1 mg/dl 26.7 % of the subjects displayed HU at the follow-up. This was associated at the multivariable analysis with female gender, office, home and 24-h blood pressure, diuretic treatment, serum triglycerides and baseline SUA, as well as the increase in waist circumference and the reduction in renal function., Conclusion: The present study provides longitudinal evidence that in the general population during a 25 year follow-up there is a progressive increase in SUA and HU development. Baseline SUA represents the most important factor associated with these modifications. Gender, renal dysfunction, triglycerides, obesity, diuretic treatment and blood pressure represent other variables capable to predict future occurrence of HU., Competing Interests: Declaration of competing interest The authors have no conflicts of interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)