Genetic and non-genetic risk factors for early-onset pancreatic cancer

Early-onset pancreatic cancer (EOPC) represents 5-10% of all pancreatic ductal adenocarcinoma (PDAC) cases, and the etiology of this form is poorly understood. It is not clear if established PDAC risk factors have the same relevance for younger patients. This study aims to identify genetic and non-genetic risk factors specific to EOPC.A genome-wide association study was performed, analysing 912 EOPC cases and 10 222 controls, divided into discovery and replication phases. Furthermore, the associations between a polygenic risk score (PRS), smoking, alcohol consumption, type 2 diabetes and PDAC risk were also assessed.Six novel SNPs were associated with EOPC risk in the discovery phase, but not in the replication phase. The PRS, smoking, and diabetes affected EOPC risk. The OR comparing current smokers to never-smokers was 2.92 (95% CI 1.69-5.04, P = 1.44 × 10-4). For diabetes, the corresponding OR was 14.95 (95% CI 3.41-65.50, P = 3.58 × 10-4).In conclusion, we did not identify novel genetic variants associated specifically with EOPC, and we found that established PDAC risk variants do not have a strong age-dependent effect. Furthermore, we add to the evidence pointing to the role of smoking and diabetes in EOPC

SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival

Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated with overall survival of pancreatic cancer patients. This study tested whether genetic variability in SLC22A3 associates with pancreatic cancer risk and prognosis. Twenty four single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene sequence and regulatory elements were selected for analysis. Of these, 22 were successfully evaluated in the discovery phase while six significant or suggestive variants entered the validation phase, comprising a total study number of 1,518 cases and 3,908 controls. In the discovery phase, rs2504938, rs9364554, and rs2457571 SNPs were significantly associated with pancreatic cancer risk. Moreover, rs7758229 associated with the presence of distant metastases, while rs512077 and rs2504956 correlated with overall survival of patients. Although replicated, the association for rs9364554 did not pass multiple testing corrections in the validation phase. Contrary to the discovery stage, rs2504938 associated with survival in the validation cohort, which was more pronounced in stage IV patients. In conclusion, common variation in the SLC22A3 gene is unlikely to significantly contribute to pancreatic cancer risk. The rs2504938 SNP in SLC22A3 significantly associates with an unfavorable prognosis of pancreatic cancer patients. Further investigation of this SNP effect on the molecular and clinical phenotype is warranted

The Activity of Special Continuity Care Units in the City of Florence During the COVID-19 Pandemic

Objectives: Worldwide, countries adopted different strategies in primary care (PC) to cope with the COVID-19 pandemic. This study aims to describe and evaluate the functions and activity load of a specific PC organizational model called “Special Continuity Care Units” (SCCU) in Florence, Italy, and to investigate the characteristics of the COVID-19 patients assisted by the service.Methods: The retrospective cross-sectional design used daily updated reports by SCCU team members to evaluate the activity load. The retrospective cohort study analyzed data of the demographics, clinical characteristics, and process outcomes of patients assisted during the second pandemic wave.Results: The analysis shows how the service activity load changed along with the epidemiological trend. Regarding people assisted by the SCCU, the median follow-up duration of symptoms was 6 days; male gender and being symptomatic were predictors of hospitalization.Conclusion: Some key characteristics can be described as indispensable in PC services facing health emergencies: model flexibility, the availability of resources, networking among services to enhance coordination and resource optimization, and close collaboration with general practitioners

Persistent Megalocystic Ovary Following in Vitro Fertilization in a Postpartum Patient with Polycystic Ovarian Syndrome

SummaryObjectiveOvarian hyperstimulation syndrome (OHSS) is more severe when pregnancy occurs, as the developing pregnancy produces human chorionic gonadotropin, which stimulates the ovary's persistent growth. If no pregnancy occurs, the syndrome will typically resolve within 1 week. In a maintained pregnancy, slow resolution of symptoms usually occurs over 1-2 months.Case ReportA 31-year-old woman, gravida 2, para 1, aborta 1, with polycystic ovary syndrome underwent in vitro fertilization (IVF) with clomiphene citrate and follicle-stimulating hormone/gonadotropin releasing hormone-antagonist stimulation. During transvaginal oocyte retrieval, enlarged bilateral ovaries were noted. She had an episode of OHSS after IVF/embryo transfer, for which paracentesis was performed three times. Pregnancy was achieved. Throughout antenatal examinations, bilateral ovaries were enlarged. She delivered a healthy baby by cesarean section at term. However, 1 month after delivery, the bilateral ovary had not shrunk, and levels of tumor markers CA125 and CA199 were 50.84 and 41.34 U/mL, respectively. At laparotomy for suspected malignancy, both adnexae formed “kissing ovaries”, which were multinodulated with yellow serous fluid. Specimens from wedge resection submitted for frozen section showed a benign ovarian cyst. The final pathology report showed bilateral follicle cysts.ConclusionWith the increasing use of gonadotropins in the management of infertility, ovarian enlargement secondary to hyperstimulation is common. Generally, symptoms appear between the 6th and 13th weeks of pregnancy and disappear thereafter. The hyperstimulated ovary often subsides after the first trimester. This case is unusual as the megalocystic ovary persisted after delivery. To the best of our knowledge, we report the first case of enlarged bilateral ovaries persisting 2 months after delivery

Malnutrition in COVID-19 survivors: prevalence and risk factors

Background: Nutritional status is a critical factor throughout COVID-19 disease course. Malnutrition is associated with poor outcomes in hospitalized COVID-19 patients. Aim: To assess the prevalence of malnutrition and identify its associated factors in COVID-19 survivors. Methods: Study cohort included 1230 COVID-19 survivors aged 18-86 attending a post-COVID-19 outpatient service. Data on clinical parameters, anthropometry, acute COVID-19 symptoms, lifestyle habits were collected through a comprehensive medical assessment. Malnutrition was assessed according to Global Leadership Initiative on Malnutrition (GLIM) criteria. Results: Prevalence of malnutrition was 22% at 4-5 months after acute disease. Participants who were not hospitalized during acute COVID-19 showed a higher frequency of malnutrition compared to those who needed hospitalization (26% versus 19%, p < 0.01). Malnutrition was found in 25% COVID-19 survivors over 65 years of age compared to 21% younger participants (p < 0.01). After multivariable adjustment, the likelihood of being malnourished increased progressively and independently with advancing age (Odds ratio [OR] 1.02; 95% CI 1.01-1.03) and in male participants (OR 5.56; 95% CI 3.53-8.74). Malnutrition was associated with loss of appetite (OR 2.50; 95% CI 1.73-3.62), and dysgeusia (OR 4.05; 95% CI 2.30-7.21) during acute COVID-19. Discussion: In the present investigation we showed that malnutrition was highly prevalent in a large cohort of COVID-19 survivors at 4-5 months from acute illness. Conclusions: Our findings highlight the need to implement comprehensive nutritional assessment and therapy as an integral part of care for COVID-19 patients

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe