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Background: Alzheimer's disease is a slowly progressing neurodegenerative illness and the most common form of dementia. This pathology leads to an increase in cognitive decline and is responsible, in patients, for several difficulties in performing various activities of daily living, such as oral hygiene. Several experimental studies have shown that oral health in patients with Alzheimer's disease worsens in direct proportion to the progression of the disease due to the appearance of gingivitis and periodontitis., Methods: This clinical literature review aims to evaluate a possible correlation between periodontal disease and Alzheimer's disease, trying to understand if the periopathogens can contribute to the onset or the progression of Alzheimer's disease (AD). The study was conducted on the database PubMed (MEDLINE) of full-text systematic reviews in English on humans and animals that were published in the last five years, from 2018 to 2023. This returned 50 publications, which, once the eligibility criteria were applied, resulted in the 10 publications examined in this review. The selected articles were organized through the construction of tables, analyzed, and compared through Judith Garrard's Matrix method to arrive at the review results., Results: Infection by periopathogens can increase the risk of developing Alzheimer's disease, but also the onset of the latter can make it more difficult to maintain proper oral hygiene, favoring the onset of periodontal disease: it is possible to affirm the existence of a correlation between periodontitis and AD. It was found that patients exposed to chronic periodontitis have a greater risk of developing a cognitive decline or AD and that oral pathogens can be responsible for neuropathologies and increasing systemic inflammation., Conclusions: Periodontitis and periodontal pathogens represent a real risk factor for the onset or worsening of AD; however, the pathogenetic mechanism is still not completely clear.

Background : Periodontal disease is an inflammatory, chronic, and multifactorial disease. The objective of this study is to analyze the association between periodontal disease and some disorders such as papillomas (benign lesions), lichen planus (a chronic immune-mediated disorder), leukoplakia (potentially malignant lesions), and oral cancer (malignant lesions). Methods : For this study, 42 patients were recruited whose supragingival and subgingival plaque was qualitatively analyzed using a phase-contrast microscope, which allowed for the detection of compatible bacterial flora (immobile and composed mainly of cocci) indicative of periodontal health and incompatible bacterial flora (mobile and composed mainly of spirochetes) indicative of periodontal pathology. Patients with incompatible bacterial flora were then subjected to a laser-assisted periodontal treatment with irrigation with hydrogen peroxide within the periodontal pockets (a non-surgical laser-assisted periodontal protocol which is referred to as dye-free photodynamic therapy). Results : Based on the 42 patients recruited, there was no association between oral cavity lesions and periodontal pathogenic bacteria. Four of them were found to have incompatible bacterial flora. Indeed, it was found that almost all the patients had been previously instructed in the proper techniques of home oral hygiene, and more than half of them reported that they carried out periodic check-ups by a dental hygienist. Of the four patients with signs and symptoms of periodontitis, two stated a willingness to undergo the non-surgical laser-assisted periodontal protocol and showed improvements in periodontal indices such as CAL, PPD, and BoP. Conclusions : hygienists and dentists are determining factors in the prevention of periodontal disease and for the maintenance of good oral health.

We prospectively studied immunological response against SARS-CoV-2 after vaccination among healthcare workers without (group A) and with previous infection (group B). The analyses were collected at T0 (before the BNT162b2), T1 (before the second dose), T2 and T6 (1 and 6 months after the second dose). For cellular immune response, the activation-induced cell marker assay was performed with CD4 and CD8 Spike peptide megapools expressed as Stimulation Index. For humoral immune response, we determined antibodies to Spike-1 and nucleocapsid protein. The linear mixed model compared specific times to T0. The CD4+ Spike response overall rate of change was significant at T1 (p = 0.038) and at T2 (p < 0.001), while decreasing at T6. For CD8+ Spike reactivity, the interaction between the time and group was significant (p = 0.0265), and the p value for group comparison was significant at the baseline (p = 0.0030) with higher SI in previously infected subjects. Overall, the anti-S Abs significantly increased from T1 to T6 compared to T0. The group B at T6 retained high anti-S titer (p < 0.001). At T6, in both groups we found a persistent humoral response and a high CD4+ T cell response able to cross recognize SARS-COV-2 variants including epsilon, even if not a circulating virus at that time.

Background: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection., Methods: This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months. The cumulative incidence of breakthrough Covid-19 cases in pwMS was calculated before and after December 2021, to separate the Delta from the Omicron waves and to account for the advent of the third vaccine dose., Findings: 1705 pwMS received 2 m-RNA vaccine doses, 21/28 days apart. Of them, 1508 (88.5%) had blood assessment 4 weeks after the second vaccine dose and 1154/1266 (92%) received the third dose after a mean interval of 210 days (range 90-342 days) after the second dose. During follow-up, 131 breakthrough Covid-19 infections (33 during the Delta and 98 during the Omicron wave) were observed. The probability to be infected during the Delta wave was associated with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.57, p < 0.001); the protective role of antibodies was preserved over the whole follow up (HR=0.57, 95%CI=0.43-0.75, p < 0.001), with a significant reduction (HR=1.40, 95%CI=1.01-1.94, p=0.04) for the Omicron cases. The third dose significantly reduced the risk of infection (HR=0.44, 95%CI=0.21-0.90,p=0.025) during the Omicron wave., Interpretation: The risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response., Funding: Supported by FISM - Fondazione Italiana Sclerosi Multipla - cod. 2021/Special-Multi/001 and financed or co-financed with the '5 per mille' public funding., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The ongoing SARS-CoV-2 pandemic requires the availability of accurate and rapid diagnostic tests, especially in such clinical settings as emergency and intensive care units. The objective of this study was to evaluate the diagnostic performance of the Vivalytic SARS-CoV-2 rapid PCR kit in lower respiratory tract (LRT) specimens., Methods: Consecutive LRT specimens (bronchoalveolar lavage and bronchoaspirates) were collected from Intensive Care Units of San Martino Hospital (Genoa, Italy) between November 2020 and January 2021. All samples underwent RT-PCR testing by means of the Allplex™ SARS-CoV-2 assay (Seegene Inc., South Korea). On the basis of RT-PCR results, specimens were categorized as negative, positive with high viral load [cycle threshold (Ct) ≤ 30] and positive with low viral load (Ct of 31-35). A 1:1:1 ratio was used to achieve a sample size of 75. All specimens were subsequently tested by means of the Vivalytic SARS-CoV-2 rapid PCR assay (Bosch Healthcare Solutions GmbH, Germany). The diagnostic performance of this assay was assessed against RT-PCR through the calculation of accuracy, Cohen's κ, sensitivity, specificity and expected positive (PPV) and negative (NPV) predictive values., Results: The overall diagnostic accuracy of the Vivalytic SARS-CoV-2 was 97.3% (95% CI: 90.9-99.3%), with an excellent Cohen's κ of 0.94 (95% CI: 0.72-1). Sensitivity and specificity were 96% (95% CI: 86.5-98.9%) and 100% (95% CI: 86.7-100%), respectively. In samples with high viral loads, sensitivity was 100% (Table 1). The distributions of E gene Ct values were similar (Wilcoxon's test: p = 0.070), with medians of 35 (IQR: 25-36) and 35 (IQR: 25-35) on Vivalytic and RT-PCR, respectively (Fig. 1). NPV and PPV was 92.6% and 100%, respectively. Table 1 Demographic characteristics and data sample type of the study cases (N = 75) Male, N (%) 56 (74.6%) Age (yr), Median (IQR) 65 (31-81) BAS, N (%) 43 (57.3%)  Negative 30.2%  Positive-High viral load [Ct ≤ 30] 27.9%  Positive-Low viral load [Ct 31-35] 41.9% BAL, N (%) 32 (42.7%)  Negative 37.5%  Positive-High viral load [Ct ≤ 30] 40.6%  Positive-Low viral load [Ct 31-35] 21.9% Data were expressed as proportions for categorical variables. Specimens were categorized into negative, positive with high viral load [cycle threshold (Ct) ≤ 30] and positive with low viral load (Ct of 31-35). BAS bronchoaspirates, BAL bronchoalveolar lavage, Ct cycle threshold Fig. 1 Distribution of E gene cycle threshold values of the rapid PCR and RT-PCR CONCLUSIONS: Vivalytic SARS-CoV-2 can be used effectively on LRT specimens following sample liquefaction. It is a feasible and highly accurate molecular procedure, especially in samples with high viral loads. This assay yields results in about 40 min, and may therefore accelerate clinical decision-making in urgent/emergency situations., (© 2021. The Author(s).)

Toxinogenic Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea. In this retrospective cohort study the molecular epidemiology of hospital-acquired and community-associated CDI was investigated in patients admitted to a tertiary care hospital. CD in stools samples was revealed by a two steps diagnostic algorithm, firstly screening for positivity to GDH antigen and thereafter RT-PCR analysis. Increased CDI incidence was observed ranging from 1.70episodes/10000patient-days in the 1st year, to 2.62 in the 2nd year, mostly hospitalized in the medicine wards, followed by outpatients (5.74 and 5.12episodes/10.000patient-days respectively). CDI positive were older than CDI negative patients and presented increased trend of diarrhea episodes as the patients' age increased. RT-PCR positive patients (n° = 314) were classified according to the CD toxin producing genes in three groups (1-3, carrying tcdB, both tcdB and cdt, and the two genes plus the deletion Δ117 of tcdC, respectively). The incidence of the group 2 and 3 increased statistically with the age of the patients showing correlation with the gender. Higher frequency of patients belonging to group 1 and group 3 was observed in the medical wards. Of note was the high incidence of group 3 in outpatients. Interestingly, patients with previous health care contacts had higher risk (RR = 1.88) of being infected by CD strains with higher toxicity than community patients. Recurrence rate was 15.9%. In conclusion the knowledge of the toxigenic profiles and of their relationships to gender, age and wards distribution may help the clinicians in the clinical management of the disease., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: To analyse the species distribution and the susceptibility profiles to the major antifungal agents of Candida isolated from bloodstream infections (BSIs) in both intensive care units (ICUs) and non-ICU wards in a tertiary care hospital in Italy from 2010 until 2015., Methodology: Episodes of Candida BSI were recorded in a retrospective observational cohort study. Yeasts were isolated from both blood and intravascuIar devices (IVDs) and their susceptibility to antifungal drugs was tested using the microdilution method., Results: 514 Candida BSIs were evidenced and 19 % of these episodes were associated with the presence of an IVD. The trend of the general incidence increased significantly throughout the study period, ranging from 1.42 to 3.63 (mean 2.52) episodes/1000 admissions. The incidence of Candida BSIs and IVD-associated candidaemia was significantly higher in ICUs relative to the other wards. The most frequently isolated species were C. albicans and C. parapsilosis complex, with the latter presenting a significant increased trend of isolation. C. parapsilosis complex was most frequently involved in IVD-related candidaemia, coinfections and late recurrent infections. Furthermore, the MIC50s of C. parapsilosis complex were significantly enhanced for echinocandins compared to the MIC50s for the same drugs and the other yeasts, while the MIC50s of C. albicans for amphotericin B showed a significant increase during the study period, ranging from 0.1 to 0.5 µg ml-1., Conclusions: A progressively enhanced incidence of Candida BSIs, a relatively high impact of C. parapsilosis complex and changes in the susceptibility profiles of the isolated yeasts were evidenced during the observation period.

Biofilm forming capacity of yeasts colonizing the intravenous devices is considered a key factor involved in the pathogenesis of Candida catheter-related bloodstream infections (CCRBSI). The biofilm production of strains of Candida spp. isolated both from the CVC and from the blood of patients with CCRBSI was compared to that of strains isolated from patients not having CCRBSI. Results, expressed in terms of Biofilm Index (BI), revealed that biofilm-producing strains were isolated in the CCRBSI group with a frequency significantly higher than in the non-CCRBSI group (χ 2 = 4.25, p = 0.03). The species more frequently cultured was C. parapsilosis complex (including C. parapsilosis sensu stricto, C. orthopsilosis and C. metapsilosis). When this species was isolated from the CVC tip cultures of the CCRBSI group it showed BIs significantly (p = 0.05) higher than those found in the non-CCRBSI group. All the strains of C. tropicalis isolated from the CCRBSI group produced biofilm. Instead most of the isolates of C. glabrata were non-producers. The cumulative BI of non-albicans Candida strains isolated from CCRBSI patients was significantly higher than that of non-albicans strains cultured from patients non-CCRBSI (χ 2 = 6.91; p = 0.008). C. albicans was a biofilm producer both in the CCRBSI and in the non-CCRBSI group. When isolated from the blood it showed enhanced biofilm production in the CCRBSI group only, while when colonizing the CVC it displayed high BIs both in the CCRBSI group and in non-CCRBSI group. Our data seem to indicate that the biofilm production capacity should be considered in the clinical management of CCRBSI.

Magnusiomyces capitatus may cause uncommon yet severe infections, especially in patients with haematologic disorders. Diagnosis may be difficult and time-consuming and newer approaches are required including the MALDI-TOF technique implemented with the detection of fungal antigens in the body fluids. The recommended treatment includes amphotericin B alone or in combination with flucytosine. We describe a case of a non-neutropenic patient with M. capitatus pleural infection, as identified by MALDI-TOF, positivity for galactomannan antigen in the BAL fluid, and successfully treated with oral posaconazole in single therapy.

Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homing of the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments.

During the last decades, several improvements in treating gynecological malignancies have been achieved. In particular, target therapies, mostly monoclonal antibodies, have emerged as an attractive option for the treatment of these malignancies. In fact, various molecular-targeted agents have been developed for a variety of malignancies with the objective to interfere with a precise tumor associated receptor, essential for cancer cell survival or proliferation, blocking its function, of the cancer cells. Alternatively, monoclonal antibodies have been developed to block immune suppression or enhance functions of immune effector cells. So far, several monoclonal antibodies have been tested for clinical efficacy for the treatment of gynecological cancers. Antibodies against Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) have been used in different neoplasms such as ovarian and cervical cancer. Catumazumab, a bivalent antibody against CD3 and EpCAM, is effective in the treatment of neoplastic ascites. Other antibodies are peculiar for specific cancer-associated antigen such as Oregovomab against CA125 or Farletuzumab against the folate receptor. Here we describe the preclinical and clinical experience gained up to now with monoclonal antibodies in tumors of the female genital tract and trace future therapeutic and research venues.

Trastuzumab's targeted therapy has become a stronghold for human epidermal growth factor receptor 2 positive breast cancer patients. This humanized monoclonal antibody binds to the extracellular juxta-membrane domain of HER2 and inhibits the proliferation and survival of HER2 dependent cancer cells. The ways by which this molecule exerts its action have been partially elucidated but several new mechanisms are being constantly identified. Several new agents are being introduced that interfere with HER2. Several new immunotherapy strategies are being introduced in order to direct the immune system against cells and tissues that aberrantly overexpressed HER2. We review the strategies currently adopted and those suggested against HER2 expressing tumors.

Surgery is the primary therapeutic strategy for most solid tumours; however, modern oncology has established that neoplasms are frequently systemic diseases. Being however a local treatment, the mechanisms through which surgery plays its systemic role remain unknown. We have investigated the influence of cytoreduction on the immune system of primary and recurrent ovarian cancer. All ovarian cancer patients show an increase in CD4+ CD25+ FOXP3+ circulating cells (CD4 T(reg) ). CD4/CD8 ratio is increased in primary tumours, but not in recurrent neoplasms. Primary cytoreduction is able to increase circulating CD4 and CD8 effector cells and decrease CD4 naïve T cells. CD4+ T(reg) cells rapidly decreased after primary tumour debulking, while CD8+ CD25+ FOXP3+ (CD8 T(reg) ) cells are not detectable in peripheral blood. Similar results on CD4 T(reg) were observed with chemical debulking in women subjected to neoadjuvant chemotherapy. CD4 and CD8 T(reg) cells are both present in neoplastic tissue. Interleukin (IL)-10 serum levels decrease after surgery, while no changes are observed in transforming growth factor-β₁ and IL-6 levels. Surgically induced reduction of the immunosuppressive environment results in an increased capacity of CD8+ T cells to respond to the recall antigens. None of these changes was observed in patients previously subjected to chemotherapy or affected by recurrent disease. In conclusion, we demonstrate in ovarian cancer that primary debulking is associated with a reduction of circulating T(reg) and an increase in CD8 T-cell function. Debulking plays a beneficial systemic effect by reverting immunosuppression and restoring immunological fitness., (© 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

Purpose: To review outcomes of arthroscopic repair of rotator cuff tears using absorbable anchors with a single-row technique., Methods: 66 patients underwent arthroscopic repair for rotator cuff tears using absorbable anchors with a single-row technique. 51 of them aged 37 to 73 (mean, 57) years had been followed up for a mean of 29 (range, 20-37) months. The extent of the tear was classified as large, medium or small. Functional outcome was assessed using the Constant score. Constant scores and re-tear rates in 3 patient groups (classified by patient age and tear size) were compared., Results: Among the 66 patients, there were 24 large, 29 medium and 13 small cuff tears, and a total of 48, 37, and 18 anchors were used, respectively. Among the 51 patients, the median Constant score improved significantly after arthroscopy (30 vs. 73, p<0.0001). Six shoulders had complete re-tears; their median Constant score was 48 and their adjusted Constant score was 65%. Complete re-tears occurred more often in patients aged >60 years than in those aged 50 to 59 years and <50 years (4/15 vs. 1/22 vs. 1/14), and more often in patients with large tears than in those with medium and small tears (4/24 vs. 2/29 vs. 0/13)., Conclusion: Arthroscopic repair of rotator cuff tears using absorbable anchors with a single-row technique is reliable in patients aged <60 years with small or medium tears.

The purpose of this study is to report the clinical and radiographic outcomes after open reduction and internal fixation of displaced proximal humerus fractures with the "Da Vinci System". It is a triangle-shaped cage whose opposite faces are pierced, and it represents the evolution of a triangle-shaped bone block technique performed in a previous series of 33 patients. The new device is an interesting innovation to treat the difficult problem of fracture fragments reconstruction and stability, metaphyseal bone loss and proximal humerus revascularization. According to the technique, authors position the correct size titanium cage into the metaepiphysis, so that the fragments are reduced upon the cage, and they are stabilized with a minimal osteosynthesis by Kirschner wires, titanium screws or transosseous sutures. If the fracture line involves the proximal portion of the diaphysis, it is possible to use a short low profile plate. Between May 2005 and November 2009, we treated 71 patients (34 men and 37 women), even though we included in our study only 59 patients, who had a minimum follow-up of 12 months. The first patient has been treated in May 2005 and the last one in September 2008. The mean age was 60.8 years (minimum 27, maximum 78). There were 8 displaced 3-part fractures, 20 displaced 4-part fractures, 10 4-part fracture-dislocations, 5 head splitting, 12 unclassified multifragmentary fractures, 1 2-part fracture with multifragmentary calcar and 3 malunions of 4-part fracture. The functional results were evaluated by the Constant score. With a mean follow-up of 24 months (minimum 12, maximum 36 months), the mean Constant score was 80.25. The results were excellent or good in 48 cases, bad in 2 cases and satisfactory in 9; the mean active anterior elevation (AAE) was 160 degrees . All fractures but one healed; in one case, we had a deep infection after 80 days since the operation, treated with a preformed cement spacer.

The incidence of multiple primary cancers has greatly increased in the last decade. We report the first case of a woman who suffered from 3 distinct HPV-induced neoplasms: cervical, vulvar, and head and neck carcinomas.

Twenty-four proximal humeral fractures were treated by surgical internal fixation with a locked antegrade intramedullary nail. The purpose of this paper was to assess the clinical outcomes of proximal epiphyseal and diaphyseal humeral fractures treated with an antegrade humeral nail implanted after an interval rotator split. We treated six proximal epiphyseal fractures and seven bifocal fractures of the epiphysis and shaft and eleven diaphyseal fractures. The mean follow-up was 23 months (range 12 to 34 months). Twenty patients were available for follow-up. All but two fractures progressed to healing. The Mean Constant score was 80%, Relative Constant score was 95.5%. We divided the clinical outcomes by fracture pattern to define the best surgical indication. There were good clinical outcomes in all three groups, but the clinical score was highest in the shaft fracture group. An intramedullary antegrade nail inserted through the interval rotator without penetrating the rotator cuff had a good clinical outcome and with certain fracture types can be an effective and satisfactory device.

Surgical treatment of complex displaced fractures of proximal humerus has changed in the last few years. Osteosynthesis has a high rate of nonunion, malunion, and avascular necrosis, and the results of hemiarthroplasty are not always functionally satisfactory. We report the results of a new technique for the reconstruction of the proximal humerus around a triangular-shaped bone block positioned inside the head and the metaphysis. The fragments are stabilized with minimal osteosynthesis by Kirschner wires, screws, or sutures. From 2001 to 2005, we treated 33 patients (20 men, 13 women) aged 34 to 74 years. The functional results were evaluated by the Constant score, with a mean follow-up of 24 months (range,12-36 months) The mean Constant score was 68 (range, 47-90). The results were excellent or good in 23 patients. The mean active anterior elevation was 160 degrees , all were pain free, and they returned to their preoperative activities, including sports. One patient had a symptomatic avascular necrosis that was treated with a hemiarthroplasty. The results show that this new technique has good clinical results with a low percentage of complications.

Background: Surgical treatment of displaced comminuted midclavicular fractures includes open reduction and stabilization with wires, pins, or screwed plates. However, it is often difficult stabilizing small fragments, and there are several complications. The aim of this study was to assess an alternative technique using a Mennen plate., Methods: From 1999 to 2004, we treated a cohort of 43 patients with a displaced three- or four-part midclavicular fracture. All patients were followed up at an average of 1 year after the injury: they had a functional evaluation and were assessed radiographically., Results: The fractures of 41 patients had healed, with two cases of nonunion and no case of infection or osteomyelitis. All of them presented normal function of the shoulder and shoulder girdle symmetry., Conclusions: A Mennen plate is a good device for the treatment of displaced midshaft clavicle fractures. The technique is simple and the operation time is shortened; the bone architecture is protected by any damage caused by drill holes; and the endosteal blood supply is preserved as a result of the paraskeletal position of the plate.