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Abstract Background Molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR) decreased mortality and hospital admissions in high-risk patients with mild to moderate COVID-19. Nevertheless, there is a lack of data about the pharmacoeconomic impact of these antivirals in the Omicron era. We conducted a pharmacoeconomic analysis assessing the medical costs of the use of these antivirals compared to those occurred in people who refused the treatment. Methods The study included the first 50 patients vaccinated against SARS-CoV-2 of each month who experienced mild to moderate COVID-19 and were consecutively treated with oral antivirals at Padua University Hospital between February 1, 2022, and June 30, 2022. In addition, all consecutive patients who met the criteria for antiviral therapy during this period but opted not to receive treatment were included as control group. The two groups were compared in terms of costs associated with emergency department visits and hospitalizations, which were identified as the primary outcomes of the study. Results Nine-hundred-sixty-one patients were analysed, mean age was 67.72 ± 15.19 years and 49% were males. The most prevalent comorbidities were cardiovascular disease (57%), obesity (18) and diabetes mellitus (18%). Two-hundred-fifty-one (26%) patients were treated with MOL (group A), 252/961 (26%) were treated with NIR (group B) and 458/961 (48%) refused antiviral therapy (group C). While a generally more favourable outcomes was observed in the early treated group, no statistically significance differences between hospitalization or emergency department visits were found between group A and C and between group B and C. Total direct medical costs were statistically significantly higher both comparing group A (671.42 ± 460€) vs. group C and comparing group B (1008.42 ± 1562€) vs. group C (446.58 ± 4977€). The main cost driver associated with the increased cost was the antiviral therapy. The average hospitalization cost was 19,334.3 ± 27,030€ for group C, 8956.2 ± 7412€ for group B and 10,267.2€ for group A. Conclusions In the context of the Omicron variant during the COVID-19 pandemic, the use of early oral antiviral agents in vaccinated individuals was found to be more expensive compared to avoid treatment, primarily due to the high costs associated with it. To enhance the efficiency in resource allocation, it is essential to pursue policies aimed at reducing drug costs, along with conducting further pharmaco-economic studies.

Background There is increasing evidence of autophagy activation in COPD, but its role is complex and probably regulated through cell type-specific mechanisms. This study aims to investigate the autophagic process at multiple levels within the respiratory system, using different methods to clarify conflicting results reported so far. Methods This cross-sectional study was performed on bronchial biopsies and peripheral lung samples obtained from COPD patients (30 and 12 per sample type, respectively) and healthy controls (25 and 22 per sample type, respectively), divided by smoking history. Subjects were matched for age and smoking history. We analysed some of the most important proteins involved in autophagosome formation, such as LC3 and p62, as well as some molecules essential for lysosome function, such as lysosome-associated membrane protein 1 (LAMP1). Immunohistochemistry was used to assess the autophagic process in both sample types. ELISA and transcriptomic analysis were performed on lung samples. Results We found increased autophagic stimulus in smoking subjects, regardless of respiratory function. This was revealed by immunohistochemistry through a significant increase in LC3 (p

Abstract Laparoscopic ventral hernia repair (LVHR) is a widely practiced treatment for primary (PH) and incisional (IH) hernias, with acceptable outcomes. Prevention of recurrence is crucial and still highly debated. Purpose of this study was to evaluate predictive factors of recurrence following LVHR with intraperitoneal onlay mesh with a single type of mesh for both PH and IH. A retrospective, multicentre study of data collected from patients who underwent LVHR for PH and IH with an intraperitoneal monofilament polypropylene mesh from January 2014 to December 2018 at 8 referral centers was conducted, and statistical analysis for risk factors of recurrence and post-operative outcomes was performed. A total of 1018 patients were collected, with 665 cases of IH (65.3%) and 353 of PH (34.7%). IH patients were older (p

The different anatomical compartments of the eye are highly subjected to reactive oxygen species (ROS) generation due to internal factors, such as metabolic high oxygen consumption, as well as environmental factors, including UV light. An antioxidant defense system is endowed in the eye tissues to regulate ROS quantity and activity. When this homeostatic system is overwhelmed, oxidative stress occurs, causing cellular damage, chronic inflammation, and tissue degeneration. It also plays a significant role in the development and progression of various ocular diseases. Understanding the mechanisms underlying oxidative stress in ocular conditions is thus crucial for the development of effective prevention and treatment strategies. To track marketed products based on antioxidant substances as active ingredients, the databases of the European Medicines Agency and the U.S. Food and Drug Administration were consulted. Only a limited number of items were identified, which were either used as therapeutic treatment or during ocular surgery, including antioxidants, synthetical derivatives, or pro-drugs designed to enhance tissue permeation and activity. This review aims to provide an overview of the primary ocular pathologies associated with oxidative stress and of the available pharmacological interventions centered around antioxidant molecules. Such insights are essential for advancing the development of effective prevention and novel treatment approaches.

Abstract Objective First-line therapy for metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has been revolutionized by the introduction of anti-checkpoint monoclonal antibodies, which have shown a significant improvement in overall survival (OS) gaining approval in a first line setting. Efficacy and safety of first-line weekly chemotherapy, compared to 3-weeks treatment, was retrospectively evaluated in a frail patient population with R/M HNSCC with the aim to evaluate its role as part of a personalized first-line approach. Methods A total of 124 patients with locally incurable R/M HNSCC receiving weekly (21) or three-weekly (103) chemotherapy plus cetuximab in a first line setting from December 2010 to September 2020 were retrospectively reviewed. Treatment outcomes in terms of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities were analysed. Results Patients in the three-week subgroup were ECOG PS 0 (39) and 1 (64) while patients in weekly group (21) were all PS 2. No significant differences were reported in terms of age, sex, smoking and previous alcohol abuse considering the two distinct subgroups. Moreover, no statistically significant difference was found in PFS and OS between the two treatment subgroups. The response rate was 35% (36 patients) and 34% (7 patients) in three-week and weekly treatment group, respectively. Seventy patients (68%) in the three-week group experienced chemotherapy-related toxicities, predominantly G3. In the weekly group a predominantly low-grade toxicity was found in a lower number of patients (52%). Conclusion The weekly schedule appears to be an active and safe strategy in frail patients with R/M HNSCC. Based on these data, a weekly schedule could be considered as a first line treatment in all frail patients excluded from pembrolizumab treatment and a study on the combination of weekly chemotherapy and immunotherapy should be performed.

Aim Evacuation through burr hole craniostomy is the most common type of chronic subdural hematoma surgical treatment, with a morbidity rate of 0-9%. Methods Here we present a case of 66-year-old Caucasian woman with bilateral hemispheric chronic subdural hematoma and left transtentorial uncal herniation. Bilateral burr hole craniostomy with gradual and simultaneous evacuation was performed and subdural drains were placed with daily strict monitoring of drained fluid. Results Despite immediate prompt neurological improvement, on the second postoperative day bilateral ptosis and left medial rectus weakness occurred, with no signs of consciousness deterioration. Radiological exams revealed a 9 x 6 mm haemorrhage of the tegmentum mesencephali. In the next day progressive neurological improvement occurred and a follow-up at 1 month revealed persistence of bilateral ptosis with almost complete regression of the left medial rectus weakness. Conclusion Although burr hole craniostomy is considered a minor procedure, rare but fatal complications like brainstem haemorrhage may occur. Bilateral simultaneous and gradual drainage, strict monitoring of drained fluid and blood pressure in the perioperative period and frequent neurological with prompt radiological assessment in case of clinical worsening, should be the mainstay of a correct management of chronic subdural hematoma (particularly if bilateral) in order to avoid potentially fatal complications.

Background Nudibranchia is an under-studied taxonomic group of gastropods, including more than 3,000 species with colourful and extravagant body shapes and peculiar predatory and defensive strategies. Although symbiosis with bacteria has been reported, no data are available for the nudibranch microbiome nor regarding viruses possibly associated with these geographically widespread species. Methods Based on 47 available RNA sequencing datasets including more than two billion reads of 35 nudibranch species, a meta-transcriptome assembly was constructed. Taxonomic searches with DIAMOND, RNA-dependent-RNA-polymerase identification with palmscan and viral hallmark genes identification by VirSorter2 in combination with CheckV were applied to identify genuine viral genomes, which were then annotated using CAT. Results A total of 20 viral genomes were identified as bona fide viruses, among 552 putative viral contigs resembling both RNA viruses of the Negarnaviricota, Pisuviricota, Kitrinoviricota phyla and actively transcribing DNA viruses of the Cossaviricota and Nucleocytoviricota phyla. The 20 commonly identified viruses showed similarity with RNA viruses identified in other RNA-seq experiments and can be putatively associated with bacteria, plant and arthropod hosts by co-occurence analysis. The RNA samples having the highest viral abundances showed a heterogenous and mostly sample-specific distribution of the identified viruses, suggesting that nudibranchs possess diversified and mostly unknown viral communities.

Aim The use of PecS block 1 as perioperative analgesia for a central catheter removal -reimplantation combined procedure. Methods A 55-year-old woman suffering from peritoneal metastases from gastric cancer needed to have a port-a-cath implanted for infection removed and to have a central venous catheter (CVC) implanted in the homolateral axillary vein due to patient’s history of deep vein thrombosis of the right upper limb. We used PECS 1 block for perioperative analgesia. Results Compared to the traditional catheter implantation technique, reduction in the doses of local anaesthetics, shortening in the execution time, less intra-procedural bleeding, better patient’s compliance, and no need for a rescue dose of local anaesthetic were observed. Conclusion The PEC1 block was effectively and safely used to remove an infected port-a-cath and to place a CVC on the same side. We hypothesize that it may be useful also for simple port-a-cath positioning.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a viral infection involving multi-organ manifestations. The main oral symptoms of COVID-19 associated are taste loss and xerostomia, but literature has reported other oral manifestation, such as oral blisters, ulcers, vesicles and other immunological lesions. This case report showed an Erythema Multiforme (EM) manifesting as oral mucosa lesions in a patient with a late diagnosis of COVID-19 infection. Case Presentation: A 30 years-old Caucasian woman was sent to an oral medicine office, in order to manage painful and oral mucosa lesions associated with target symmetrical skin lesions. Oral examination revealed extensive ulcers in the mouth and crusts on the lips. Based on clinical examinations, a diagnosis of Erythema Multiforme major was made and a drug therapy with steroids was administered. Five days after the specialist visit, the patient discovered that she was positive for COVID-19. The complete recovery occurred in 3 weeks. Conclusion: Confirming the literature studies, EM is an early disease associated with COVID-19 infection.

Objective: To assess evidence on the efficacy of adjuvant human papillomavirus (HPV) vaccination in patients treated for HPV-related disease across different susceptible organ sites. Methods: A systematic review was conducted to identify studies addressing the efficacy of adjuvant HPV vaccination on reducing the risk of recurrence of HPV-related preinvasive diseases. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Results: Sixteen studies were identified for the final analysis. Overall, 21,472 patients with cervical dysplasia were included: 4132 (19.2%) received the peri-operative HPV vaccine, while 17,340 (80.8%) underwent surgical treatment alone. The recurrences of CIN 1+ (OR 0.45, 95% CI 0.27 to 0.73; p = 0.001), CIN 2+ (OR 0.33, 95% CI 0.20 to 0.52; p < 0.0001), and CIN 3 (OR 0.28, 95% CI 0.13 to 0.59; p = 0.0009) were lower in the vaccinated than in unvaccinated group. Similarly, adjuvant vaccination reduced the risk of developing anal intraepithelial neoplasia (p = 0.005) and recurrent respiratory papillomatosis (p = 0.004). No differences in anogenital warts and vulvar intraepithelial neoplasia recurrence rate were observed comparing vaccinated and unvaccinated individuals. Conclusions: Adjuvant HPV vaccination is associated with a reduced risk of CIN recurrence, although there are limited data regarding its role in other HPV-related diseases. Further research is warranted to shed more light on the role of HPV vaccination as adjuvant therapy after primary treatment.

The neuromuscular junction is exposed to different types of insult, including mechanical trauma, toxins and autoimmune antibodies and, accordingly, has retained through evolution a remarkable ability to regenerate. Regeneration is driven by multiple signals that are exchanged among the cellular components of the junction. These signals are largely unknown. Miller Fisher syndrome is a variant of Guillain–Barré syndrome caused by autoimmune antibodies specific for epitopes of peripheral axon terminals. Using an animal model of Miller Fisher syndrome, we recently reported that a monoclonal anti-polysialoganglioside GQ1b antibody plus complement damages nerve terminals with production of mitochondrial hydrogen peroxide, which activates Schwann cells. Several additional signaling molecules are likely to be involved in the activation of the regeneration program in these cells. Using an in vitro cellular model consisting of co-cultured primary neurons and Schwann cells, we found that ATP is released by neurons injured by the anti-GQ1b antibody plus complement. Neuron-derived ATP acts as an alarm messenger for Schwann cells, where it induces the activation of intracellular pathways, including calcium signaling, cAMP and CREB, which, in turn, produce signals that promote nerve regeneration. These results contribute to defining the cross-talk taking place at the neuromuscular junction when it is attacked by anti-gangliosides autoantibodies plus complement, which is crucial for nerve regeneration and is also likely to be important in other peripheral neuropathies.

Chronic kidney disease (CKD) is very often among diabetic patients. Some oral antidiabetic agents are not recommended in the presence of CKD. Aim of the study was to evaluate the quality of diabetes mellitus (DM) treatment in nephrophatic patients in the real world. A total of 265 subjects with type 2 DM, consecutively admitted to the internal medicine departments of two hospitals in Rome, were recruited. Patients hospitalized for hypoglycemia, decompensated DM, acute kidney failure or worsening nephropathy were excluded. For each patient, the following data were collected: age, gender, estimated glomerular filtration rate (eGFR) using the MDRD (modification of diet in renal disease) study equation, type of antidiabetic drug treatment. A total of 265 subjects were studied, 127 male (47.9%) and 138 female (52.1%). The mean age was 77.5 years. The mean of glycemia glycated hemoglobin (HbA1c) value was 57.5 mmol/mol (7.4%). 137 patients (51.7%) were treated with oral antidiabetic agents, 29 (10%) with both oral antidiabetic agents and insulin, 90 (34%) with insulin alone, 8 (3%) with dipeptidyl peptidase-4 inhibitors, 1 (0.4%) with incretin agents plus oral antidiabetic drugs. According to the Kidney Disease Outcomes Quality Initiative (KDOQI) classification of CKD, the sample was divided into 5 groups using eGFR criteria. For each group, mean HbA1c values, type of antidiabetic treatment, appropriateness of therapy according to guidelines and how it may affect the HbA1c levels were considered. Our data show that 30.5% of patients with CKD stage 3-5 is treated with drugs not recommended by current guidelines.

BackgroundTo analyze pathologic and perioperative outcomes of laparoscopic vs. open resections for rectal cancer performed over the last 10 years.MethodsA systematic literature search of the following databases was conducted: Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), EMBASE, and Scopus. Only articles published in English from January 1, 2008 to December 31, 2018 (i.e. the last 10 years), which met inclusion criteria were considered. The review only included articles which compared Laparoscopic rectal resection (LRR) and Open Rectal Resection (ORR) for rectal cancer and reported at least one of the outcomes of interest. The analyses followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement checklist. Only prospective randomized studies were considered. The body of evidence emerging from this study was evaluated using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. Outcome measures (mean and median values, standard deviations, and interquartile ranges) were extracted for each surgical treatment. Pooled estimates of the mean differences were calculated using random effects models to consider potential inter-study heterogeneity and to adopt a more conservative approach. The pooled effect was considered significant if p ResultsFive clinical trials were found eligible for the analyses. A positive involvement of CRM was found in 49 LRRs (8.5%) out of 574 patients and in 30 ORRs out of 557 patients (5.4%) RR was 1.55 (95% CI, 0.99-2.41; p = 0.05) with no heterogeneity (I2 = 0%). Incorrect mesorectal excision was observed in 56 out of 507 (11%) patients who underwent LRR and in 41 (8.4%) out of 484 patients who underwent ORR; RR was 1.30 (95% CI, 0.89-1.91; p = 0.18) with no heterogeneity (I2 = 0%). Regarding other pathologic outcomes, no significant difference between LRR and ORR was observed in the number of lymph nodes harvested or concerning the distance to the distal margin. As expected, a significant difference was found in the operating time for ORR with a mean difference of 41.99 (95% CI, 24.18, 59.81; p ConclusionDespite the spread of laparoscopy with dedicated surgeons and the development of even more precise surgical tools and technologies, the pathological results of laparoscopic surgery are still comparable to those of open ones. Additionally, concerning the pathological data (and particularly CRM), open surgery guarantees better results as compared to laparoscopic surgery. These results must be a starting point for future evaluations which consider the association between ''successful resection" and long-term oncologic outcomes. The introduction of other minimally invasive techniques for rectal cancer surgery, such as robotic resection or transanal TME (taTME), has revealed new scenarios and made open and even laparoscopic surgery obsolete.

Objective The aim of the analysis is to assess the organisational and economic consequences of adopting an early discharge strategy for the treatment of acute bacterial skin and skin structure infection (ABSSSI) and osteomyelitis within infectious disease departments.Setting Infectious disease departments in Greece, Italy and Spain.Participants No patients were involved in the analysis performed.Interventions An analytic framework was developed to consider two alternative scenarios: standard hospitalisation care or an early discharge strategy for patients hospitalised due to ABSSSI and osteomyelitis, from the perspective of the National Health Services of Greece, Italy and Spain. The variables considered were: the number of annual hospitalisations eligible for early discharge, the antibiotic treatments considered (ie, oral antibiotics and intravenous long-acting antibiotics), diagnosis-related group (DRG) reimbursements, number of days of hospitalisation, incidence and costs of hospital-acquired infections, additional follow-up visits and intravenous administrations. Data were based on published literature and expert opinions.Primary and secondary outcome measures Number of days of hospitalisation avoided and direct medical costs avoided.Results The total number of days of hospitalisation avoided on a yearly basis would be between 2216 and 5595 in Greece (−8/−21 hospital beds), between 15 848 and 38 444 in Italy (−57/−135 hospital beds) and between 7529 and 23 520 in Spain (−27/−85 hospital beds). From an economic perspective, the impact of the early discharge scenario is a reduction between €45 036 and €149 552 in Greece, a reduction between €182 132 and €437 990 in Italy and a reduction between €292 284 and €884 035 in Spain.Conclusions The early discharge strategy presented would have a positive organisational impact on National Health Services, leading to potential savings in beds, and to a reduction of hospital-acquired infections and costs.

Odontogenic infections have the potential to develop into deep-space infections and may cause severe diseases with possible life-threatening complications. Dental infections during pregnancy require special attention in terms of possible complications and treatments due to the potential to affect the lives of two individuals. A case of a 36-year-old pregnant patient with a submandibular abscess caused by an odontogenic infection is reported, followed by a comprehensive systematic review of the literature in order to retrieve information regarding severe odontogenic infections and adverse pregnancy outcomes. The review was conducted according to the PRISMA guidelines using PubMed, Scopus, and Google Scholar databases. A total of 69 cases were included in the qualitative analysis. The mean age was 27.72 years. Patients were managed with surgery in combination with antibiotics. Nine infectious-related cesarean sections were detected, and preterm birth was associated in 3 cases, low birth weight in 2 cases, death of the fetus in 9 cases (13%), and maternal death in 4 cases (5.8%). The possible compromise of oral health during pregnancy is well known; however, severe odontogenic infections are rarely considered in the literature, and they may be associated with severe and life-threatening complications for both mother and the fetus.

Purpose: The aim of this study was to analyze the thermal damage in dental implants after irradiations with a 980nm diode laser, normally used for the decontamination. Material and Methods: Five Titanium Plasma Sprayed dental implants were irradiated with a 980nm diode laser at different parameters. Temperature increase on implant surface was evaluated by a Mid-Wavelength Infrared thermal-camera (Merlin®, FLIR, USA). Temperature increase (ΔT) was compared to environmental temperature (27°C) and recorded in three points: “A” (laser spot), “B” (3mm apically to the laser spot) and “C” (2mm horizontally to the laser spot). Finally, a morphological evaluation at optical stereomicroscopy was performed. Results: When 0.6W power was applied, a moderate increase of temperature in point A (5.5°C-15.0°C), a slight increase in point B (0.1°C-6.2°C) and point C (0.1°C-5.7°C), were registered after 30” of irradiation. In the samples treated at 6W, in “point A” an impressive ΔT increase was immediately recorded (over 70°C). In “point B” was recorded a slight ΔT after 2 sec. irradiation (range 2.3°C-6.0°C), a moderate ΔT after 4 sec. irradiation (16.4°C) and a consistent ΔT after 8-10 sec. irradiation (range 36.6°C-46.2°C). In “point C” ΔT values were very similar to those collected in “point B”. Optical stereomicroscopy examination at a magnification of 32x did not show any surface alteration or damage after whichever laser irradiation independently from irradiation time and power output . Conclusions: 980nm diode laser, used at controlled parameters, can be used in the decontamination of dental implants, without causing any thermal damage or increase.

Background: Psoriasis is a chronic inflammatory genodermatosis characterized by erythemato-squamous lesions. In literature, few cases of psoriasis affecting oral mucous membranes are reported. Materials and methods: a case of a 72-years-old woman with persistent burning symptoms on the dorsum of the tongue with an erythematous squamous area was reported. An oropharyngeal swab and a scalpel incisional biopsy were performed. Results: Histopathological examination described the presence of hyperparakeratosis, acanthosis, papillomatosis and Munro microabscesses. Clinical and histopathological findings are compatible with a diagnosis of oral psoriasis. Conclusions: Psoriasis lesion rarely affects oral mucosa. When it occurs, it is important a cooperation between oral pathologist and dermatologist.

Every season, circulating influenza viruses change; therefore, vaccines must be reformulated each year. We aimed to estimate vaccine effectiveness (VE) against severe influenza infection for the 2018/19 season in Italy. We conducted a test-negative design case-control study at five Italian hospitals. We estimated influenza VE against severe acute respiratory infection (SARI) requiring hospitalisation overall, and by virus subtype, vaccine brand, and age. The 2018/19 season was characterised by A(H1N1)pmd09 and A(H3N2) influenza viruses. Vaccine coverage among

Concurrent chemotherapy and radiotherapy (cCRT) is considered the standard treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Unfortunately, management is still heterogeneous across different specialists. A multidisciplinary approach is needed in this setting due to recent, promising results obtained by consolidative immunotherapy. The aim of this survey is to assess current LA-NSCLC management in Italy. From January to April 2018, a 15-question survey focusing on diagnostic/therapeutic LA-NSCLC management was sent to 1,478 e-mail addresses that belonged to pneumologists, thoracic surgeons, and radiation and medical oncologists. 421 answers were analyzed: 176 radiation oncologists, 86 medical oncologists, 92 pneumologists, 64 thoracic surgeons and 3 other specialists. More than a half of the respondents had been practicing for >10 years after completing residency training. Some discrepancies were observed in clinical LA-NSCLC management: the lack of a regularly planned multidisciplinary tumor board, the use of upfront surgery in multistation stage IIIA, and territorial diffusion of cCRT in unresectable LA-NSCLC. Our analysis demonstrated good compliance with international guidelines in the diagnostic workup of LA-NSCLC. We observed a relationship between high clinical experience and good clinical practice. A multidisciplinary approach is mandatory for managing LA-NSCLC.

BACKGROUND:There are several treatments available to newly diagnosed prostate cancer (PCA) patients. Although surgery and radiotherapy (RT) with or without androgen deprivation therapy (ADT) are widely adopted treatment options for localized PCA together with active surveillance (AS), there is no consensus nor randomised trials on treatment selection, prospective quality of life (QOL), along with toxicity outcomes and according to treatment modality in the Italian population. The current study aimed to describe clinical-therapeutic features and QOL at PCA diagnosis, according to different treatment patterns in a large prospective, Italian population, enrolled in the Pros-IT CNR study. METHODS:The Pros-IT CNR is an on-going national, multicenter, observational, prospective study on patients affected by PCA who have been referred by 97 Italian Urology, Radiation Oncology and Medical Oncology facilities participating in the project. The possible relationships between the treatment patterns reported in the 6 month follow-up case report form and patients' features at diagnosis were evaluated using exploratory multiple correspondence analysis (MCA) and other data analysis method. RESULTS:At diagnosis, surgery and AS patients were significantly younger, had fewer comorbidities, lower PSA levels and Gleason Score (GS) values; they were also diagnosed at an earlier stage of disease with respect to the RT or ADT patients who showed significantly worse QoL scores at the time of diagnosis. CONCLUSIONS:An analysis of the data collected at baseline and 6 months later uncovered substantial differences in ages, comorbidities, clinical and QOL features in the various treatment groups. These findings do not fully reflect the current PCA treatment guidelines and suggest the need for a multidisciplinary consensus guideline to ameliorate both the counselling and treatments of PCA patients.

The hospital internal medicine (IM) needs to adapt to the socio-demographic changes occurred during the last thirty years: patients currently show an increased overall complexity owing to the increase in the average age of the patients admitted, to more several and severe comorbidities, and a higher concentration in our wards of most severe cases. Our departments have to change in order to pursue a more efficient organization and to offer care to users modulated according to their needs and conditions. The Intensity of Care in Internal Medicine Group of the Federation of Associations of Hospital Doctors on Internal Medicine - Lazio carried out a population-based study in eight Internal Medicine wards of the region with the aim of characterizing the patients there admitted, using the modified early warning score (mEWS), monitoring and evaluating the outcomes of hospitalization. This has allowed us to determine the cut-off of the score indicating a greater statistical probability of a fatal outcome corresponding to 3, contrary to what originally reported by Subbe et al. in 2001. According to our results into the Departments of IM should be provided an area of high care, where monitor and stabilize the patients admitted with a mEWS score ≥3, before transferring them to the wards of lower intensity of care. This organizational model of the high care of medical patients has the benefit of offer the technical and professional assistance appropriate to the level of clinical risk, with more intensive care to more critical stages of illness.

BACKGROUND:Primary central nervous system (CNS) solitary fibrous tumour/hemangiopericytoma (SFT/HPC) is a rare neoplasm and its classification criteria have been redefined by the latest WHO Classification of CNS Tumours. Outcome can vary significantly among patients, thus reliable prognostic markers are warranted. METHODS:Primary CNS SFT/HPC diagnosed at the Pathology Unit of our Institution between 2006 and 2016 were retrospectively collected. Tumour grade along with immunohistochemistry for Ki67, STAT6, PHH3, CD34 and Bcl-2 were assessed. TERT promoter status was evaluated by Sanger sequencing. RESULTS:Fifteen SFT/HPC were analysed: 9/15 (60%) female, median age at diagnosis 60 (range: 10-67). Six (40%) cases showed a SFT phenotype and mean H&E-mitotic count was 4.8/10 HPF. Tumour grade was I in 6, II in 4 and III in 5 cases. Mean PHH3-mitotic count was higher than H&E count (8.4 versus 4.8/10 HPF), but it would have determined a change in tumour grade in a sole case. Nuclear staining for STAT6 was present in 14/15 (93.3%). CD34 and Bcl-2 expression rates were lower in higher grade tumours. TERT promoter was mutated in two cases. Median follow up time was 2.4 years (6 months-7.4 years) and 5/15 (33%) patients developed local disease recurrence. Partial resection (p = 0.0185), higher WHO grade (p = 0.038), lower CD34 (p = 0.038) and Bcl-2 (p = 0.010) expressions were significantly associated with a poorer disease-free interval. CONCLUSIONS:WHO grade is the main prognostic tool in CNS SFT/HPC, but it could be integrated by other markers, like CD34 and Bcl-2, in the clinical practice. The relevance of TERT promoter mutations in this subset of CNS tumours needs further evaluation.

Osteonecrosis of the jaws (ONJ) is an uncommon but severe bone disease, can be related to various medicaments (MRONJ) including bisphosphonates (BRONJ), antiangiogenic and antiresorptive medicaments such as Denosumab (DRONJ), human monoclonal antibody to the receptor activator of nuclear factor-kB ligand. The rise in number in the latest years can be explained with many patients treated with all these drugs, assumed for osteometabolic (i.e osteoporosis, osteogenesis imperfecta) or neoplastic diseases (multiple myeloma, metastatic breast, prostate and renal cancer). The onset mechanism of MRONJ is not entirely understood, probably different mechanisms are involved, such as inhibition of the osteoclasts differentiation and function, decrease of the angiogenesis and inflammation/infection of the jaw bones. Some pathogenetic mechanisms are different according to the drugs, for example the cases of the RANK-ligand inhibitor related ONJ may occur without considering the period of medication intake; also the risk of ONJ manifestation after bisphosphonates (BF) is not significantly diminished after interrupting the drug therapy, because BF bind to the bone matrix for many years. Drugs currently implicated in osteonecrosis pathology are various, therefore the term ONJ was currently replaced by MRONJ; it is necessary that the anamnestic phase and management of the patients to be more detailed and correct, not only to prevent osteonecrosis but also to plan all necessary treatments before start of the drug therapy.

Background: The objective of this study was to evaluate, by means of elemental analysis the mineral density, calcium, and phosphorus weight percent of sound enamel, demineralized and CPP-ACP treated enamel. Elemental analysis allows elemental and isotopic composition of a biologic sample. It can be qualitative (determining what elements are present), and quantitative (determining how much of each are present). INCA Energy 250, Oxford Analytical Instruments Ltd. (UK), energy-dispersive X-ray spectroscopy system for elemental analysis was performed on random assigned samples. Methods: 12 sound premolars were extracted for orthodontic reason. Each tooth was sectioned by using a double-faced diamond microtome under water cooling into three section for a total of 36 samples and randomly assigned to three groups: Group 1 (control), Group 2 (WS: white spot) , Group 3 (WST white spot treated) of 12 samples each. Samples (Group 2 and Group 3) underwent equally to 24 h and 48 h of acid bath duration. Then all the treated samples (Group 3) were coated with CPP-ACP for 5 min before immersion into water twice a day. Group 2 served as control for enamel damage evaluation. Inca Point & ID, an analytic platform software for SEM was used for elemental analysis on samples from Group 1 (C), 2 (WS) and Group 3 (WST) in order to determine the weight % and atomic % presence of Ca and P. Results: The results of the samples analysis from the three Groups show different weight % and atomic% of Ca and P, and clearly reflect the different mineralization rates. Conclusions: 10% Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) complex, promotes remineralization in vitro. The results of this in vitro study completely agree with this statement. Clinical studies to investigate the intraoral effectiveness of topical applications of CPP-ACP on white spot lesions are required to confirm these results.

The central giant cells granuloma (CGCG) is a benign intraosseous lesion of the jaws. CGCG is found predominantly in childrenand young adults, most commonly in the anterior portion of the mandible. Although many theories have been proposed to explain theaetiology and pathogenesis of CGCG, its true nature is still unknown. In this study, two cases of CGCG are presented.The first case is about a 7-year-old patient with a lesion of the mandible and the ectopic displacement of teeth n° 3.2 and n° 7.4.The second case is about a 68-year-old man with a recidivant lesion of the mandible, that produced an external root resorption of3.3, in the same site of a previously excised CGCG. In both cases a surgical excision of the lesion was performed and a histologicaldiagnosis of CGCG was made. The clinical and radiographic 4-years follow-up in the first case and a 2-years follow-up in the secondcase did not reveal any recurrence of the lesion. So we may conclude that early and precise diagnosis of CGCG allows conservativemanagement without risks for the adjacent teeth or bone.

The efficacy of azoxystrobin was evaluated in the presence of mycotoxigenic fungi and relative mycotoxins in Italian paddy rice during the growing season in the field. Three experimental fields were considered and the applied experimental design was a strip plot with three replicates; rice samples were collected at four different growing stages. The efficacy of the fungicide treatment on rice fungal population was demonstrated with around 20% less total fungal incidence in sprayed samples compared to untreated ones; the same decrease was noted also in Fusarium spp. species but not in Aspergillus versicolor. Of the mycotoxins considered, ochratoxin A (OTA) and aflatoxins (AFBs) were never detected, deoxynivalenol (DON) was found in 46% of samples at levels always lower than 100 µg/kg, while sterigmatocystin (STC) occurred in all the paddy rice samples collected after flowering, with a maximum value of 15.5 µg/kg. Treatment with azoxystrobin was not effective in reducing DON contamination, but it had an important and significant effect on STC content, showing a decrease of 67% in the sprayed samples.

Emphysematous pyelonephritis is a severe, life-threatening, necrotizing kidney disease. It occurs almost exclusively in patients with diabetes mellitus. The clinical manifestations are those of pyelonephritis such as dysuria, fever, nausea, vomiting and abdominal pain. The diagnosis is radiological. The treatment strategies are controversial. They include medical management only, percutaneous catheter drainage plus medical management, emergency nephrectomy plus medical treatment or percutaneous drainage plus medical management and emergency nephrectomy. We present the case of a 68-year-old woman affected by emphysematous pyelonephritis successfully managed with conservative medical treatment.

Small non-coding RNAs include powerful regulators of gene expression, transposon mobility and virus activity. Among the various categories, mature microRNAs (miRNAs) guide the translational repression and decay of several targeted mRNAs. The biogenesis of miRNAs depends on few gene products, essentially conserved from basal to higher metazoans, whose protein domains allow specific interactions with dsRNA. Here, we report the identification of key genes responsible of the miRNA biogenesis in 32 bivalves, with particular attention to the aquaculture species Mytilus galloprovincialis and Crassostrea gigas. In detail, we have identified and phylogenetically compared eight evolutionary conserved proteins: DROSHA, DGCR8, EXP5, RAN, DICER TARBP2, AGO and PIWI. In mussels, we recognized several other proteins participating in the miRNA biogenesis or in the subsequent RNA silencing. According to digital expression analysis, these genes display low and not inducible expression levels in adult mussels and oysters whereas they are considerably expressed during development. As miRNAs play an important role also in the antiviral responses, knowledge on their production and regulative effects can shed light on essential molecular processes and provide new hints for disease prevention in bivalves.

BACKGROUND:Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. MATERIAL AND METHODS:A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. RESULTS:A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, p< 0.01 and p = 0.006, respectively). Thirty of the 32 biopsies co-expressing both markers had partial or absent tumor response (TRG 2-5), strengthening their positive predictive value (94%). The exclusive predictive role of YKL-40 and c-Met was confirmed using a multivariate analysis (p = 0.004 and p = 0.007 for YKL-40 and c-Met, respectively). TRG was the sole morphological parameter associated with poor outcome. CONCLUSION:c-Met and YKL-40 expression is a reliable predictor of partial/absent response to neoadjuvant CRT in rectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

Atmospheric pressure cold plasma (APCP) might be considered a novel tool for tissue disinfection in medicine since the active chemical species produced by low plasma doses, generated by ionizing helium gas in air, induces reactive oxygen species (ROS) that kill microorganisms without substantially affecting human cells.In this study, we evaluated morphological and functional changes in human corneas exposed for 2 minutes (min) to APCP and tested if the antioxidant n-acetyl l-cysteine (NAC) was able to inhibit or prevent damage and cell death.Immunohistochemistry and western blotting analyses of corneal tissues collected at 6 hours (h) post-APCP treatment demonstrated no morphological tissue changes, but a transient increased expression of OGG1 glycosylase that returned to control levels in 24 h. Transcriptome sequencing and quantitative real time PCR performed on different corneas revealed in the treated corneas many differentially expressed genes: namely, 256 and 304 genes showing expression changes greater than ± 2 folds in the absence and presence of NAC, respectively. At 6 h post-treatment, the most over-expressed gene categories suggested an active or enhanced cell functioning, with only a minority of genes specifically concerning oxidative DNA damage and repair showing slight over-expression values (

Introduction. Oral biopsy aims to obtain clear and safe diagnosis; it can be performed by scalpel or laser. The controversy in this latter application is the thermal alteration due to tissue heating. The aim of this study is the histological evaluation of margins of “in vivo” biopsies collected by diode and KTP lasers. Material and Methods. 17 oral benign lesions biopsies were made by diode 808 nm (SOL, DenMatItalia, Italy) and KTP 532 nm (SmartLite, DEKA, Italy). Samples were observed at OM LEICA DM 2000; margin alterations were evaluated through Leica Application Suite 3.4. Results. Epithelial and connective damages were assessed for each pathology with an average of 0.245 mm and a standard deviation of ±0.162 mm in mucoceles, 0.382 mm ± 0.149 mm in fibromas, 0.336 mm ± 0.106 mm in hyperkeratosis, 0.473 mm ± 0.105 mm in squamous hyperplasia, 0.182 mm in giant cell granuloma, and 0.149 mm in melanotic macula. Discussion. The histologic aspect of lesions influenced the response to laser, whereas the greater inflammation and cellularity were linked with the higher thermal signs. Many artifacts were also associated to histologic procedures. Conclusion. Both tested lasers permitted sure histologic diagnosis. However, it is suggested to enlarge biopsies of about 0.5 mm, to avoid thermal alterations, especially in inflammatory lesions like oral lichen planus.

ObjectiveTo estimate the lifetime cost utility of two antiretroviral regimens (once-daily atazanavir plus ritonavir [ATV+r] versus twice-daily lopinavir/ritonavir [LPV/r]) in Italian human immunodeficiency virus (HIV)-infected patients naïve to treatment.DesignWith this observational retrospective study we collected the clinical data of a cohort of HIV-infected patients receiving first-line treatment with LPV/r or ATV+r.MethodologyA Markov microsimulation model including direct costs and health outcomes of first- and second-line highly active retroviral therapy was developed from a third-party (Italian National Healthcare Service) payer's perspective. Health and monetary outcomes associated with the long-term use of ATV+r and LPV/r regimens were evaluated on the basis of eight health states, incidence of diarrhoea and hyperbilirubinemia, AIDS events, opportunistic infections, coronary heart disease events and, for the first time in an economic evaluation, chronic kidney disease (CKD) events. In order to account for possible deviations between real-life data and randomised controlled trial results, a second control arm (ATV+r 2) was created with differential transition probabilities taken from the literature.ResultsThe average survival was 24.061 years for patients receiving LPV/r, 24.081 and 24.084 for those receiving ATV+r 1 and 2 respectively. The mean quality-adjusted life-years (QALYs) were higher for the patients receiving LPV/r than those receiving ATV+r (13.322 vs. 13.060 and 13.261 for ATV+r 1 and 2). The cost-utility values were 15,310.56 for LPV/r, 15,902.99 and 15,524.85 for ATV+r 1 and 2.ConclusionsUsing real-life data, the model produced significantly different results compared with other studies. With the innovative addition of an evaluation of CKD events, the model showed a cost-utility value advantage for twice-daily LPV/r over once-daily ATV+r, thus providing evidence for its continued use in the treatment of HIV.

ObjectiveStevens-Johnson Syndrome (SJS) is one of the most severe muco-cutaneous diseases and its occurrence is often attributed to drug use. The aim of the present study is to quantify the risk of SJS in association with drug and vaccine use in children.MethodsA multicenter surveillance of children hospitalized through the emergency departments for acute conditions of interest is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from all admissions. Parents were interviewed on child's use of drugs and vaccines preceding the onset of symptoms that led to the hospitalization. We compared the use of drugs and vaccines in cases with the corresponding use in a control group of children hospitalized for acute neurological conditions.ResultsTwenty-nine children with a diagnosis of SJS and 1,362 with neurological disorders were hospitalized between 1(st) November 1999 and 31(st) October 2012. Cases were more frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4; 95% CI 1.0-6.1). Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI 8.4-86.0). Significantly elevated risks were also estimated for antibiotics use (adjusted OR 3.3; 95% CI 1.5-7.2), corticosteroids (adjusted OR 4.2; 95% CI 1.8-9.9) and paracetamol (adjusted OR 3.2; 95% CI 1.5-6.9). No increased risk was estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3-2.8).DiscussionOur study provides additional evidence on the etiologic role of drugs and vaccines in the occurrence of SJS in children.

Aiming at an integrated and mechanistic view of the early biological effects of selected metals in the marine sentinel organism Mytilus galloprovincialis, we exposed mussels for 48 hours to 50, 100 and 200 nM solutions of equimolar Cd, Cu and Hg salts and measured cytological and molecular biomarkers in parallel. Focusing on the mussel gills, first target of toxic water contaminants and actively proliferating tissue, we detected significant dose-related increases of cells with micronuclei and other nuclear abnormalities in the treated mussels, with differences in the bioconcentration of the three metals determined in the mussel flesh by atomic absorption spectrometry. Gene expression profiles, determined in the same individual gills in parallel, revealed some transcriptional changes at the 50 nM dose, and substantial increases of differentially expressed genes at the 100 and 200 nM doses, with roughly similar amounts of up- and down-regulated genes. The functional annotation of gill transcripts with consistent expression trends and significantly altered at least in one dose point disclosed the complexity of the induced cell response. The most evident transcriptional changes concerned protein synthesis and turnover, ion homeostasis, cell cycle regulation and apoptosis, and intracellular trafficking (transcript sequences denoting heat shock proteins, metal binding thioneins, sequestosome 1 and proteasome subunits, and GADD45 exemplify up-regulated genes while transcript sequences denoting actin, tubulins and the apoptosis inhibitor 1 exemplify down-regulated genes). Overall, nanomolar doses of co-occurring free metal ions have induced significant structural and functional changes in the mussel gills: the intensity of response to the stimulus measured in laboratory supports the additional validation of molecular markers of metal exposure to be used in Mussel Watch programs.

Introduction The number of autoptic controls is progressively dropping worldwide during the last decades. Several social, cultural and normative causes may underlie this phenomenon. However, a hidden cause may be represented by the scepticism of physicians about the gain in information given by this practice. There is in fact a general thinking that available diagnostic techniques may be adequate for a correct diagnosis, even in the case of a mortal outcome. Nevertheless, several studies have shown quite relevant discrepancies between premortem and postmortem diagnosis. In this study, the authors evaluate the accuracy of clinical diagnosis in diseases leading the patient to death.Materials and methods Retrospective analysis including all patients died in the Department of Internal Medicine of a General Hospital in Rome during a three year time period (1st January 2007–31 December 2009). Age, sex, period of hospitalization, clinical diagnosis, autoptic diagnosis, cause of death, and level of discrepancy between clinical diagnosis and autoptic control have been collected. Main diagnoses have been classified as follows: (1) discrepancy with a possible influence on survival; (2) discrepancy with no or questionable influence on survival.Results Ninety-two cases (42 males, 50 females; mean age 79.3 years) have been included. Thirty-four main diagnoses (36.9%) have been classified as discrepant (15.2% classified as type 1 discrepancy and 21.7 as type 2).DiscussionA substantial discrepancy between clinical diagnosis and autoptic control is confirmed by the current study, which supports the role of autopsy as a tool for the improvement of medical practice.

BACKGROUND: Effective innate responses against potential pathogens are essential in the living world and possibly contributed to the evolutionary success of invertebrates. Taken together, antimicrobial peptide (AMP) precursors of defensin, mytilin, myticin and mytimycin can represent about 40% of the hemocyte transcriptome in mussels injected with viral-like and bacterial preparations, and unique profiles of myticin C variants are expressed in single mussels. Based on amplicon pyrosequencing, we have ascertained and compared the natural and Vibrio-induced diversity of AMP transcripts in mussel hemocytes from three European regions. METHODOLOGY/PRINCIPAL FINDINGS: Hemolymph was collected from mussels farmed in the coastal regions of Palavas (France), Vigo (Spain) and Venice (Italy). To represent the AMP families known in M. galloprovincialis, nine transcript sequences have been selected, amplified from hemocyte RNA and subjected to pyrosequencing. Hemolymph from farmed (offshore) and wild (lagoon) Venice mussels, both injected with 10(7) Vibrio cells, were similarly processed. Amplicon pyrosequencing emphasized the AMP transcript diversity, with Single Nucleotide Changes (SNC) minimal for mytilin B/C and maximal for arthropod-like defensin and myticin C. Ratio of non-synonymous vs. synonymous changes also greatly differed between AMP isotypes. Overall, each amplicon revealed similar levels of nucleotidic variation across geographical regions, with two main sequence patterns confirmed for mytimycin and no substantial changes after immunostimulation. CONCLUSIONS/SIGNIFICANCE: Barcoding and bidirectional pyrosequencing allowed us to map and compare the transcript diversity of known mussel AMPs. Though most of the genuine cds variation was common to the analyzed samples we could estimate from 9 to 106 peptide variants in hemolymph pools representing 100 mussels, depending on the AMP isoform and sampling site. In this study, no prevailing SNC patterns related to geographical origin or Vibrio injection emerged. Whether or not the contact with potential pathogens can increase the amount of AMP transcript variants in mussels requires additional study.