Antibody levels after BNT162b2 vaccine booster and SARS-CoV-2 Omicron infection

In the present study, immunogenicity data in 61 vaccinated healthcare workers (HCWs) either infection naïve (naïve HCWs) or with infection of Delta and/or Omicron COVID-19 (experienced HCWs) were evaluated up to 270 days after the second dose of BNT162b2 vaccine and up to 90 days after a booster dose. A decrease in antibody levels at 270 days following administration of the second dose (p = 0.0335) was observed, although values did not fall below the positivity threshold (33.8 BAU/ml). After booster vaccination, antibody levels increased after 30 days (p = 0.0486), with much higher values than after first and second vaccination. Antibody levels then decreased at 60 and 90 days after the booster dose. A comparison between mean antibody levels of naïve and experienced HCWs revealed higher values in experienced HCWs, resulting from both natural and vaccination-induced immunity. A total of 14.7% of HCWs contracted the Omicron virus variant after the vaccine booster, although none showed severe symptoms. These results support that a booster dose results in a marked increase in antibody response that subsequently decreases over time

Increased Risk of Hereditary Prostate Cancer in Italian Families with Hereditary Breast and Ovarian Cancer Syndrome Harboring Mutations in BRCA and in Other Susceptibility Genes

Hereditary prostate cancer (HPCa) has the highest heritability of any cancer in men. Interestingly, it occurs in several hereditary syndromes, including breast and ovarian cancer (HBOC) and Lynch syndrome (LS). Several gene mutations related to these syndromes have been identified as biomarkers in HPCa. The goal of this study was to screen for germline mutations in susceptibility genes by using a multigene panel, and to subsequently correlate the results with clinical and laboratory parameters. This was undertaken in 180 HBOC families, which included 217 males with prostate cancer (PCa). Mutational analysis was further extended to 104 family members of mutated patients. Screening of HBOC families revealed that 30.5% harbored germline mutations in susceptibility genes, with 21.6% harboring pathogenic variants (PVs) and 8.9% having variants of uncertain significance (VUS). We found PVs at similar frequency in BRCA1 and BRCA2 genes (8.8% and 9.4%, respectively), while 0.56% of PVs were present in well-established susceptibility genes PALB2, TP53 and RAD51C. Moreover, 0.56% of monoallelic PVs were present in MUTYH, a gene whose function in tumorigenesis in the context of PCa is still unclear. Finally, we reported double heterozygosity (DH) in BRCA1/2 genes in a single family, and found double mutation (DM) present in BRCA2 in a separate family. There was no significant difference between the mean age of onset of PCa in HBOC families with or without germline mutations in susceptibility genes, while the mean survival was highest in mutated patients compared to wild type. Furthermore, PCa is the second most recurrent cancer in our cohort, resulting in 18% of cases in both mutated and non-mutated families. Our investigation shows that PVs were located mostly in the 3′ of BRCA1 and BRCA2 genes, and in BRCA2, most PVs fell in exon 11, suggesting a mutation cluster region relating to risk of HPCa. A total of 65 family members inherited the proband’s mutation; of these, 24 developed cancer, with 41 remaining unaffected

Polygraphic findings in simplified Barbed Reposition Pharyngoplasty (BRP) as a treatment for OSA patients

This study aims to compare polygraphic data in patients with OSA treated with Barbed Reposition Pharyngoplasty (BRP) performed with a simplified technique compared to the standard method. Variations of technique were performed and tested with the purpose of promoting tolerability and diffusion of this simplified technique. To evaluate the efficacy of the simplified BRP method, a sample of 99 patients was divided into two groups: Group A was treated with BRP (BRP group) and Group B was treated with simplified BRP (sBRP group). The results obtained on the two groups were compared with the two sample Bootstrap t-tests method, showing a substantial overlap in polygraphic results recorded 6 months after surgery

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Diagnostic utility of FGF-23 in mineral bone disorder during chronic kidney disease

Our data confirm that intact fibroblast growth factor 23 (iFGF-23) concentration is increased in patients with chronic kidney disease (CKD) and that it increases with disease progression (stages I-V). Therefore, iFGF-23 could be considered an early biomarker in the course of chronic kidney disease-mineral bone disorder (CKD-MBD), which has several aspects that make it potentially useful in clinical practice. The availability of an automated method for iFGF-23 assay may represent an added value in the management of the patient with CKD-MBD already from the early stages of the disease, before the increase of the routinely used laboratory parameters, 1-84 parathyroid hormone (PTH) and 25-OH-vitamin D (25-OH-vitD), which occur in more advanced stages of the disease

Prevalence of mutations in BRCA and MMR genes in patients affected with hereditary endometrial cancer

Endometrial cancer (EC) is the fifth most common cancer in women from developed countries, accounting for 4.8% of new cases and 2.1% of deaths. The genetic basis for the familial risk of endometrial cancer has not been completely defined. Mostly, hereditary EC is part of two syndromes as Lynch syndrome (LS) and Hereditary Breast and Ovarian Cancer syndrome (HBOC). LS is the prototypical hereditary cancer syndrome in EC and accounts for 2-6% of all endometrial cancers. This disease is caused by autosomal dominant mutations in DNA mismatch repair (MMR) genes. Patients carrying a germline mutation in one of the MMR genes have a cumulative lifetime risk to develop EC of 20-70%. HBOC is an autosomal dominantly inherited disease, which mostly predisposes to breast and ovarian cancers, but it can be also associated with other malignancies. HBOC results from germline mutations in BRCA1/2 genes. The aim of this study was to determine the mutational status of a cohort of 40 EC patients, 19 belonging to families with LS and 21 to HBOC. Mutation analysis of MLH1, MSH2, BRCA1 and BRCA2 genes showed pathogenic variants in 17/40 (42.5%) patients. Out of 19 patients belonging to LS families, 8 (42.1%) showed a pathogenic variant. Out of 21 patients belonging to HBOC families, 9 (42.8%) showed a pathogenic variant. 1/21 (4.8%) patient report 1 variant of unknown significance (UV), c.599 C > T (p.T200I), in BRCA2. Moreover, in 1/21 (4.8%) patient we identified a novel missense variant in BRCA2, c.9541A > T (p.Met3181Leu). Mutational analysis was extended to family members, both healthy and cancer affected, of mutated patients; all the tested relatives affected with cancer displayed the pathogenic variant. Our data suggest that patients with hereditary EC have a high percentage of mutations in the LS and HBOC main susceptibility genes; therefore, the surveillance for EC, already indicated in LS patients, should also be recommended for patients with HBOC

Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention

Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed

Bdellovibrio bacteriovorus directly attacks Pseudomonas aeruginosa and Staphylococcus aureus Cystic fibrosis isolates

Bdellovibrio bacteriovorus is a predator bacterial species found in the environment and within the human gut, able to attack Gram-negative prey. Cystic fibrosis (CF) is a genetic disease which usually presents lung colonization by Pseudomonas aeruginosa or Staphylococcus aureus biofilms. Here, we investigated the predatory behavior of B. bactenovorus against these two pathogenic species with: (1) broth culture; (2) "static" biofilms; (3) field emission scanning electron microscope (FESEM); (4) "flow" biofilms; (5) zymographic technique. We had the first evidence of B. bacteriovorus survival with a Gram-positive prey, revealing a direct cell-to-cell contact with S. aureus and a new "epibiotic" foraging strategy imaged with FESEM. Mean attaching time of HD100 to S. aureus cells was 185s, while "static" and "flow" S. aureus biofilms were reduced by 74 (at 24h) and 46% (at 20h), respectively. Furthermore, zymograms showed a differential bacteriolytic activity exerted by the B. bacteriovorus lysates on P aeruginosa and S. aureus. The dual foraging system against Gram-negative (periplasmic) and Gram-positive (epibiotic) prey could suggest the use of B. bacteriovorus as a "living antibiotic" in CF, even if further studies are required to simulate its in vivo predatory behavior

Butyrate as bioactive human milk protective component against food allergy

Background Food allergy (FA) is a growing health problem worldwide. Effective strategies are advocated to limit the disease burden. Human milk (HM) could be considered as a protective factor against FA, but its mechanisms remain unclear. Butyrate is a gut microbiota-derived metabolite able to exert several immunomodulatory functions. We aimed to define the butyrate concentration in HM, and to see whether the butyrate concentration detected in HM is able to modulate the mechanisms of immune tolerance.Methods HM butyrate concentration from 109 healthy women was assessed by GS-MS. The effect of HM butyrate on tolerogenic mechanisms was assessed in in vivo and in vitro models.Results The median butyrate concentration in mature HM was 0.75 mM. This butyrate concentration was responsible for the maximum modulatory effects observed in all experimental models evaluated in this study. Data from mouse model show that in basal condition, butyrate up-regulated the expression of several biomarkers of gut barrier integrity, and of tolerogenic cytokines. Pretreatment with butyrate significantly reduced allergic response in three animal models of FA, with a stimulation of tolerogenic cytokines, inhibition of Th2 cytokines production and a modulation of oxidative stress. Data from human cell models show that butyrate stimulated human beta defensin-3, mucus components and tight junctions expression in human enterocytes, and IL-10, IFN-gamma and FoxP3 expression through epigenetic mechanisms in PBMCs from FA children. Furthermore, it promoted the precursors of M2 macrophages, DCs and regulatory T cells.Conclusion The study's findings suggest the importance of butyrate as a pivotal HM compound able to protect against FA

Butyrate as a bioactive human milk protective component against food allergy

Background Food allergy (FA) is a growing health problem worldwide. Effective strategies are advocated to limit the disease burden. Human milk (HM) could be considered as a protective factor against FA, but its mechanisms remain unclear. Butyrate is a gut microbiota-derived metabolite able to exert several immunomodulatory functions. We aimed to define the butyrate concentration in HM, and to see whether the butyrate concentration detected in HM is able to modulate the mechanisms of immune tolerance.Methods HM butyrate concentration from 109 healthy women was assessed by GS-MS. The effect of HM butyrate on tolerogenic mechanisms was assessed in in vivo and in vitro models.Results The median butyrate concentration in mature HM was 0.75 mM. This butyrate concentration was responsible for the maximum modulatory effects observed in all experimental models evaluated in this study. Data from mouse model show that in basal condition, butyrate up-regulated the expression of several biomarkers of gut barrier integrity, and of tolerogenic cytokines. Pretreatment with butyrate significantly reduced allergic response in three animal models of FA, with a stimulation of tolerogenic cytokines, inhibition of Th2 cytokines production and a modulation of oxidative stress. Data from human cell models show that butyrate stimulated human beta defensin-3, mucus components and tight junctions expression in human enterocytes, and IL-10, IFN-gamma and FoxP3 expression through epigenetic mechanisms in PBMCs from FA children. Furthermore, it promoted the precursors of M2 macrophages, DCs and regulatory T cells.Conclusion The study's findings suggest the importance of butyrate as a pivotal HM compound able to protect against FA