The cardiovascular risk of young women with polycystic ovary syndrome: an observational, analytical, prospective case-control study

To evaluate the cardiovascular risk of polycystic ovary syndrome (PCOS), we investigated lipid profile, metabolic pattern, and echocardiography in 30 young women with PCOS and 30 healthy age- and body mass index (BMI)-matched women. PCOS women had higher fasting glucose and insulin levels, homeostasis model assessment score of insulin sensitivity, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels, and TC/high density lipoprotein cholesterol (HDL-C) ratio and lower HDL-C levels than controls. Additionally, PCOS women had higher left atrium size (32.0 +/- 4.9 vs. 27.4 +/- 2.1 mm; P < 0.0001) and left ventricular mass index (80.5 +/- 18.1 vs. 56.1 +/- 5.4 g/m(2); P < 0.0001) and lower left ventricular ejection fraction (64.4 +/- 4.1 vs. 67.1 +/- 2.6%; P = 0.003) and early to late mitral flow velocity ratio (1.6 +/- 0.4 vs. 2.1 +/- 0.2; P < 0.0001) than controls. When patients and controls were grouped according to BMI [normal weight (BMI, >18 and <25 kg/m(2)), overweight (BMI, 25.1-30 kg/m(2)), and obese (BMI, >30 kg/m(2))], the differences between PCOS women and controls were maintained in overweight and obese women. In normal weight PCOS women, a significant increase in left ventricular mass index and a decrease in diastolic filling were observed, notwithstanding no change in TC, LDL-C, HDL-C, TC/HDL-C ratio, and TG compared with controls. In conclusion, our data show the detrimental effect of PCOS on the cardiovascular system even in young women asymptomatic for cardiac disease

Effects of different degrees of sympathetic antagonism on cytokine network in patients with ischemic dilated cardiomyopathy

BACKGROUND: The proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Recent studies have shown that beta-adrenergic blockade can modulate cytokine production. This study investigates the different impact of different degrees of sympathetic antagonism on circulating levels of cytokines in patients with heart failure resulting from ischemic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Thirty-five patients with IDC were randomly assigned to receive metoprolol or carvedilol in an open-label study. Echocardiographic measurements and circulating levels of tumor necrosis (TNF)-alpha and interleukin (IL)-1beta and IL-6 were obtained at baseline and after 3 months of treatment. The 2 beta-blockers significantly improved the left ventricular ejection fraction and reduced end-diastolic and end-systolic volume. The magnitude of these changes was greater with carvedilol than with metoprolol (respectively P < .001, P < .05, and P < .05). Both treatments induced a significant decrease in the levels of cytokines (for all P < .01), but the decrease in TNF-alpha and IL-1beta was more consistent in the carvedilol group ( P < .01). CONCLUSION: Our results support the hypothesis that a more complete block of sympathetic activity by carvedilol induces a greater decrease in the circulating levels of proinflammatory cytokines that could explain, at least in part, the better improvement in the left ventricular remodelling and systolic function in patients with IDC

Reliable Fast (20 Hz) Acquisition Rate by a TD fNIRS Device: Brain Resting-State Oscillation Studies

A high power setup for multichannel time-domain (TD) functional near infrared spectroscopy (fNIRS) measurements with high efficiency detection system was developed. It was fully characterized based on international performance assessment protocols for diffuse optics instruments, showing an improvement of the signal-to-noise ratio (SNR) with respect to previous analogue devices, and allowing acquisition of signals with sampling rate up to 20 Hz and source-detector distance up to 5 cm. A resting-state measurement on the motor cortex of a healthy volunteer was performed with an acquisition rate of 20 Hz at a 4 cm source-detector distance. The power spectrum for the cortical oxy- and deoxyhemoglobin is also provided

Role of serial cardiac 18F-FDG PET-MRI in Anderson-Fabry disease: a pilot study

Aim: We investigated the value of serial cardiac 18F-FDG PET-MRI in Anderson–Fabry disease (AFD) and the potential relationship of imaging results with FASTEX score. Methods and results: Thirteen AFD patients underwent cardiac 18F-FDG PET-MRI at baseline and follow-up. Coefficient of variation (COV) of FDG uptake and FASTEX score were assessed. At baseline, 9 patients were enzyme replacement therapy (ERT) naïve and 4 patients were under treatment. Two patients presented a FASTEX score of 0 indicating stable disease and did not show any imaging abnormality at baseline and follow-up PET-MRI. Eleven patients had a FASTEX score > 20% indicating disease worsening. Four of these patients without late gadolinium enhancement (LGE) and with normal COV at baseline and follow-up had a FASTEX score of 35%. Three patients without LGE and with abnormal COV at baseline and follow-up had a FASTEX score ranging from 30 to 70%. Three patients with LGE and abnormal COV at baseline and follow-up had a FASTEX score between 35 and 75%. Finally, one patient with LGE and normal COV had a FASTEX score of 100%. Of the 12 patients on ERT at follow-up, FASTEX score was significantly higher in those 4 showing irreversible cardiac injury at baseline compared to 8 with negative LGE (66 ± 24 vs. 32 ± 21, p = 0.03). Conclusion: 18F-FDG PET-MRI may be effective to monitor cardiac involvement in AFD

Comparison between Rapid Intraoperative and Central Laboratory Parathormone Dosage in 12 Kidney Transplant Candidates

Background The rapid intraoperative parathormone (PTH) and at central laboratory PTH dosage gives similar results. The central laboratory provides results in longer times and higher costs. Intraoperative measurement can reduce time and costs during parathyroidectomy. Methods Twelve patients undergoing parathyroidectomy for hyperparathyroidism renal transplant candidates were included. Diagnosis was made by laboratory tests (serum calcium, PTH) and imaging techniques (ultrasonography and scintigraphy). All patients presented PTH levels of >400 pg/mL (the limit value to be maintained in list for kidney transplantation) and resistant to medical therapy. For each patient, 2 blood samples were collected before surgery at anesthesia induction for PTH testing intraoperative (rapid assay) and central laboratory, and 10 minutes after the removal of each gland. The times from collection-processing to communication to the surgeon of the results were compared for both the methods. It was considered successful the abatement of PTH of ≥70% at rapid intraoperative testing and consequently surgical intervention stopped before communication of central laboratory PTH testing. Results The average time of reporting the test results of the central laboratory was 41.5 minutes (SD ± 9), whereas with the rapid intraoperative PTH (ioPTH) testing the average time was 9.9 minutes (SD ± 2.02). An average of 33.6 minutes of the duration per intervention (SD ± 10.27) were virtually saved with the use of ioPTH testing. The 2 values of the Pearson correlation (ρ) of 0.99 obtained (for baseline) and 0.975 (for the 10-minute) lead us to conclude that there is an excellent correlation between the series of data. Conclusions Rapid ioPTH testing, owing to its accuracy, permits a dramatic reduction of operating time for patients with secondary hyperparathyroidism that need to be treated before inclusion on the waiting list

Combination of chemotherapy and PD-1 blockade induces T cell responses to tumor non-mutated neoantigens

Here, we developed an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens (NM-neoAgs). Indeed, only the fragmented proteins elicited effective multi-specific CD4+ and CD8+ T cell responses, upon a chemotherapy protocol including CDDP. Importantly, these responses further increased upon anti-PD-1 therapy, and correlated with patients’ survival and decreased PD-1 expression. Cross-presentation assays showed that NM-neoAgs were unveiled in apoptotic tumor cells as the result of caspase-dependent proteolytic activity of cellular proteins. Our study demonstrates that apoptotic tumor cells generate a repertoire of immunogenic NM-neoAgs that could be potentially used for developing effective T cell-based immunotherapy across multiple cancer patients

Combination of chemotherapy and PD-1 blockade induces T cell responses to tumor non-mutated neoantigens

Grimaldi and Cammarata et al. develop a proteomics-based, target discovery platform to identify immunogenic proteins specific to apoptotic tumor cells. This study highlights the importance of protein modifications in apoptotic tumor cells as a mechanism of generating immunogenic neoantigens that can be targeted for T cell-based immunotherapy.Here, we developed an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens (NM-neoAgs). Indeed, only the fragmented proteins elicited effective multi-specific CD4(+) and CD8(+) T cell responses, upon a chemotherapy protocol including CDDP. Importantly, these responses further increased upon anti-PD-1 therapy, and correlated with patients' survival and decreased PD-1 expression. Cross-presentation assays showed that NM-neoAgs were unveiled in apoptotic tumor cells as the result of caspase-dependent proteolytic activity of cellular proteins. Our study demonstrates that apoptotic tumor cells generate a repertoire of immunogenic NM-neoAgs that could be potentially used for developing effective T cell-based immunotherapy across multiple cancer patients

Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p &lt;0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p &lt;0.0001), age (OR 1.03 per year, p &lt;0.001), hypertension (OR 2.30, p &lt;0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020