COVID-19 Vaccination in Health Care Workers in Italy: A Literature Review and a Report from a Comprehensive Cancer Center.

The coronavirus disease 2019 pandemic still represents a global public health emergency, despite the availability of different types of vaccines that reduced the number of severe cases, the hospitalization rate and mortality. The Italian Vaccine Distribution Plan identified healthcare workers (HCWs) as the top-priority category to receive access to a vaccine and different studies on HCWs have been implemented to clarify the duration and kinetics of antibody response. The aim of this paper is to perform a literature review across a total of 44 studies of the serologic response to COVID-19 vaccines in HCWs in Italy and to report the results obtained in a prospective longitudinal study implemented at the Fondazione IRCCS Istituto Nazionale Tumori (INT) of Milan on 1565 HCWs. At INT we found that 99.81% of the HCWs developed an antibody response one month after the second dose. About six months after the first serology evaluation, 100% of the HCWs were still positive to the antibody, although we observed a significant decrease in its levels. Overall, our literature review results highlight a robust antibody response in most of the HCWs after the second vaccination dose. These figures are also confirmed in our institutional setting seven months after the completion of the cycle of second doses of vaccination.

Weighing the prognostic role of hyponatremia in hospitalized patients with metastatic solid tumors: the HYPNOSIS study.

Previous works linked low sodium concentration with mortality risk in cancer. We aimed at weighing the prognostic impact of hyponatremia in all consecutive patients with metastatic solid tumors admitted in a two-years period at our medical oncology department. Patients were included in two cohorts based on serum sodium concentration on admission. A total of 1025 patients were included, of whom 279 (27.2%) were found to be hyponatremic. The highest prevalence of hyponatremia was observed in biliary tract (51%), prostate (45%) and small-cell lung cancer (38.9%). With a median follow-up of 26.9 months, median OS was 2 months and 13.2 months for the hyponatremia versus control cohort, respectively (HR, 2.65; P < 0.001). In the multivariable model, hyponatremia was independently associated with poorer OS (HR, 1.66; P < 0.001). According to the multivariable model, a nomogram system was developed and validated in an external set of patients. We weighed over time the influence of hyponatremia on survival of patients with metastatic solid tumors and pointed out the possibility to exploit serum sodium assessment to design integrated prognostic tools. Our study also highlights the need for a deeper characterization of the biological role of extracellular sodium levels in tumor development and progression.

A Pilot Low-Inflammatory Dietary Intervention to Reduce Inflammation and Improve Quality of Life in Patients With Familial Adenomatous Polyposis: Protocol Description and Preliminary Results.

Patients with familial adenomatous polyposis (FAP) depend on a lifelong endoscopic surveillance programme and prophylactic surgery, and usually suffer nutritional problems. Intestinal inflammation has been linked to both FAP and colorectal cancer. Epidemiological studies show a relationship between diet and inflammation. Preventive dietary recommendations for FAP patients are so far lacking. We have designed a nonrandomized prospective pilot study on FAP patients to assess whether a low-inflammatory diet based on the Mediterranean diet principles and recipes, by interacting with the microbiota, reduces gastrointestinal markers of inflammation and improves quality of life. This report describes the scientific protocol of the study and reports the participants' adherence to the proposed dietary recommendations. Thirty-four FAP patients older than 18 years, bearing the APC pathogenic variant, who underwent prophylactic total colectomy with ileo-rectal anastomosis were eligible into the study. During the 3-month dietary intervention, they reported improvements in their consumption of Mediterranean foods (vegetables, fruits, fish, and legumes), and a reduction in pro-inflammatory foods (red/processed meat and sweets); this led to a significant increase in their adherence to the Mediterranean diet. The improvement was accompanied by a decrease in the number of diarrhoeal discharges. These preliminary results are encouraging with regard to feasibility, dietary outcome measures, and safety.

Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study.

BACKGROUND: The differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients. METHODS: Markers were dosed before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) by enzyme-linked immunosorbent assay (ELISA) in 30 DMPM patients and 14 controls with other PSMs. Receiver-operating characteristics (ROC) curve were plotted. The performance of each marker was assessed by the area under the ROC curve (AUC-ROC). RESULTS: Mean mesothelin levels were 7.84 ng/dl (SD = 5.14) in DMPM group and 3.00 ng/dl (SD = 1.25) in controls (P = 0.001). Mean CEA levels were 5.3 ng/dl (SD = 4.7), and 61.96 ng/dl (SD = 112.5) in the two groups (P = 0.008). No statistical difference was seen for osteopontin (P = 0.738), CA19.9 (P = 0.081), CA125 (P = 0.600), and CA15.3 (P = 0.365). AUC-ROC was 0.836 for CA19.9, 0.812 for mesothelin, 0.793 for CEA, and lower for CA125 (0.652), osteopontin (0.531), and CA15.3 (0.481). Using diagnostic cut-offs selected by ROC methodology, sensitivity, specificity, positive and negative predictive values were 70.0%, 100.0%, 100.0%, and 60.9% for mesothelin >5.21 ng/dl, and 90.0%, 85.7%, 93.1%, and 80.0% for CA19.9 < 8.8 U/dl. At multivariate analysis, osteopontin correlated with survival (hazard rate 6.46; 95%CI 1.81-23.05; P = 0.004). CONCLUSION: When assessing PSMs of unknown origin, elevated mesothelin with low CA19.9 may increase the suspicion index for DMPM. Ospeopontin warrants further investigations as a prognostic marker for DMPM.

Adherence to Mediterranean Diet and Metabolic Syndrome in BRCA Mutation Carriers.

BACKGROUND: Insulin resistance is associated with higher breast cancer (BC) penetrance in BRCA mutation carriers. Metabolic syndrome (MetS), an insulin resistance syndrome, can be reversed by adhering to the Mediterranean diet (MedDiet). In a dietary intervention trial on BRCA mutation carriers, we evaluated adherence to the MedDiet, and the association with the MetS, by analyzing data from the Mediterranean Diet Adherence Screener (MEDAS). METHODS: BRCA mutation carriers, with or without BC, aged 18 to 70 years, were eligible for the trial. After the baseline examinations, women were randomized to a dietary intervention or to a control group. Both groups completed the MEDAS at baseline and at the end of the dietary intervention. RESULTS: A total of 163 women completed the 6 months of dietary intervention. Compared with controls, the women in the intervention group significantly reduced their consumption of red meat ( P < .01) and commercial sweets ( P < .01) and their MEDAS score rose significantly (+1.3 vs +0.55, P = .02). The number of MetS parameters decreased with increasing points of adherence to the MEDAS score ( P = .01). In the intervention group, there was a significant association with the greater reduction of MetS. CONCLUSION: BRCA mutation carriers in the intervention group experienced greater improvement in their MedDiet and MetS parameters.

Influence of lignans depletion on murine mammary gland morphology.

Different studies have focused on the effects of phytoestrogens-supplemented diets on mammary gland morphogenesis and breast cancer risk; however, particular dieting behaviors and food choices may result in a reduction of the natural source of phytoestrogens. The evaluation of a reduced phytoestrogens intake effect by depletion without modifying other dietary ingredients is hard. Since lignans, the largest contributors to phytoestrogens intake in Western diets, are metabolized into bioactive compounds by gut bacteria, long-term antibiotic treatments, inducing intestinal microflora disruption, may reduce enterolactone availability. To elucidate the effect of phytoestrogens lack on mammary tissue morphogenesis, female FVB mice were treated with gentamicin or metronidazole/ciprofloxacin from the age of 6 to 7 wk. After 21 wk, enterolactone urine levels were 120.07 +/- 20.5 ng/ml in untreated mice, 30.4 +/- 24.46 ng/ml in metronidazole/ciprofloxacin-treated mice, and 3.29 +/- 4.38 ng/ml in gentamicin-treated mice. Histological analysis revealed no significant alterations of mammary morphology in metronidazole/ciprofloxacin-treated mice, whereas gentamicin-treated mice showed increase of ducts number and duct-tree branching vs. controls. These findings indicate that normal mammary tissue size and shape are maintained even in the presence of low levels of lignans and suggest that only a complete depletion of these compounds induced significant alterations of mammary gland structure.

Equol status modifies the association of soy intake and mammographic density in a sample of postmenopausal women.

Only 30% to 50% of people produce the daidzein-metabolite equol after eating soy. We conducted a cross-sectional study of the associations between equol status, intake of soy foods, and mammographic density in a sample of postmenopausal women recruited at a radiology clinic near Buffalo, New York. Participants were 48 to 82 years old, had no history of cancer or breast reduction/augmentation, and no recent use of antibiotics or hormones. Percent density was measured by computer-assisted analysis of digitized images of craniocaudal films. Equol status was assessed using a soy-challenge protocol and usual soy intake by questionnaire. General linear models were used to assess independent and joint effects of equol status and intake of soy on multivariate adjusted percent density (covariates included age, body mass index, parity, age at first birth, and ever use of combined hormone therapy). Of 325 enrolled, 232 (71%) participants completed study assessments and are included in the present analysis. Mean percent density was 34% (+/-18%). Seventy-five (30%) participants were producers of equol. Forty-three (19%) participants reported regularly eating >1 soy food or supplement/wk. There were no significant independent associations of equol status or soy intake with percent density, but the interaction between these factors was significant (P < 0.01). Among equol producers, those with weekly soy intake had lower percent density (30.7% in weekly consumers of soy versus 38.9% in others; P = 0.08); among nonproducers, weekly soy intake was associated with higher percent density (37.5% in weekly soy consumers versus 30.7% in others; P = 0.03). Results suggest that equol producers and nonproducers may experience different effects of dietary soy on breast tissue.

Influence of antibiotic treatment on breast carcinoma development in proto-neu transgenic mice.

The effect of prolonged antibiotic treatments on tumor development was evaluated in proto-neu transgenic mice, which spontaneously develop mammary carcinomas. Virgin transgenic mice were treated with metronidazole/ciprofloxacin or gentamicin through the drinking water. The hazard ratio [HR; 95% confidence interval (95% CI)] of breast cancer occurrence in metronidazole/ciprofloxacin-treated mice was more than triple that for controls [3.11 (1.13-8.53); P = 0.028], whereas only a slight increase in HR (95% CI) was observed in gentamicin-treated mice [1.39 (0.56-3.47); P = 0.481]. Tumor growth rate in gentamicin-treated mice was significantly faster than in untreated control mice (P = 0.043). Moreover, mammary glands from mice treated with either antibiotic regimen showed increased lobulization, with more numerous and more developed terminal ductal lobular units than in controls. These results indicate that prolonged exposure to relevant doses of antibiotics affects the mammary glands in this particular model of HER-2/neu transgenic mice; further studies to understand the precise mechanism by which antibiotic treatments influence mammary gland differentiation are critical.