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Human leishmaniasis is facing important epidemiological changes in Southern Europe, driven by increased urbanization, climate changes, emerging of new animal reservoirs, shifts in human behavior and a growing population of immunocompromised and elderly individuals. In this evolving epidemiological landscape, we analyzed the clinical and epidemiological characteristics of human leishmaniasis in the Tuscany region of Central Italy. Through a multicentric retrospective analysis, we collected clinical and demographic data about all cases of leishmaniasis recorded between 2018 and 2023. We observed 176 cases of human leishmaniasis, with 128 (72.7%) visceral leishmaniasis (VL) and 47 (26.7%) cutaneous leishmaniasis (CL). Among these, 92.2% of VL and 85.1% of CL cases were autochthonous. The cumulative incidence of autochthonous human leishmaniasis was 0.22 cases per 100,000 inhabitants in 2018, but reached 1.81/100,000 in 2023. We identified three main areas of transmission: around the city of Florence (North-East Tuscany), around Grosseto city (South-West Tuscany) and Elba Island. Our findings confirm that the epidemiology of leishmaniasis is undergoing significant changes in Central Italy. Awareness towards this emerging health threat and surveillance strategies need to be improved in order to reliably assess the disease's burden. Further research is needed in a "One-Health" perspective, to clarify the epidemiological dynamics at the environmental, reservoir, vector and human levels. The role of climate change and specific climatic factors affecting the epidemiological patterns of human leishmaniasis should be assessed. Further knowledge in these fields would promote targeted control and prevention strategies at regional and national levels.

Biallelic mutations in the RPE65 gene affect nearly 8% of Leber Congenital Amaurosis and 2% of Retinitis Pigmentosa cases. Voretigene neparvovec (VN) is the first gene therapy approach approved for their treatment. To date, real life experience has demonstrated functional improvements following VN treatment, which are consistent with the clinical trials outcomes. However, there is currently no consensus on the characteristics for eligibility for VN treatment. We reviewed relevant literature to explore whether recommendations on patient eligibility can be extrapolated following VN marketing. We screened 166 papers through six research questions, following scoping reviews methodology, to investigate: (1) the clinical and genetic features considered in VN treatment eligibility; (2) the psychophysical tests and imaging modalities used in the pre-treatment and follow-up; (3) the potential correlations between visual function and retinal structure that can be used to define treatment impact on disease progression; (4) retinal degeneration; (5) the most advanced testing modalities; and (6) the impact of surgical procedure on treatment outcomes. Current gaps concerning patients' eligibility in clinical settings, such as pre-treatment characteristics and outcomes are not consistently reported across the studies. No upper limit of retinal degeneration can be defined as the univocal factor in patient eligibility, although evidence suggested that the potential for function rescue is related to the preservation of photoreceptors before treatment. In general, paediatric patients retain more viable cells, present a less severe disease stage and show the highest potential for improvements, making them the most suitable candidates for treatment., (© 2024. The Author(s).)

Background: Acute left-sided colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in the acute setting. Currently, the most popular classifications, based on radiological findings, are the modified Hinchey, American Association for the Surgery of Trauma (AAST), and World Society of Emergency Surgery (WSES) classifications. We hypothesize that all classifications are equivalent in predicting outcomes., Methods: This is a retrospective study of 597 patients from four medical centers between 2014 and 2021. Based on clinical, radiological, and intraoperative findings, patients were graded according to the three classifications. Regression analysis and receiver operating characteristic curve analysis were used to compare six outcomes: need for intervention, complications, major complications (Clavien-Dindo >2), reintervention, hospital length of stay, and mortality., Results: A total of 597 patients were included. Need for intervention, morbidity, and reintervention rates significantly increased with increasing AAST, modified Hinchey, and WSES grades. The area under the curve (AUC) for the need for intervention was 0.84 for AAST and 0.81 for modified Hinchey ( p = 0.039). The AUC for major complications was 0.75 for modified Hinchey and 0.70 for WSES ( p = 0.009). No differences were found between the three classifications when comparing AUCs for mortality, complications, and reintervention rates., Conclusion: The AAST, WSES, and modified Hinchey classifications are similar in predicting complications, reintervention, and mortality rates. American Association for the Surgery of Trauma and modified Hinchey scores result the most adequate for predicting the need for surgery and the occurrence of major complications., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: Data on immunoresponse after SARS-CoV-2 vaccines for patients treated with exclusive radiotherapy (RT) are scarce. Since RT may affect the immune system, we conducted the MORA trial (Antibody response and cell-mediated immunity of MOderna mRNA-1273 vaccine in patients treated with RAdiotherapy)., Materials and Methods: Data regarding humoral and cellular immune response of patients treated with RT were prospectively collected after the second and third dose of mRNA vaccines., Results: Ninety-two patients were enrolled. With a median of 147 days after the second dose, the median SARS-CoV-2 IgG titer was 300 BAU/mL: six patients were seronegative (Spike IgG titer ≤ 40 BAU/mL), whereas 24, 46 and 16 were poor responders (Spike IgG titer:41-200 BAU/mL), responders (Spike IgG titer:201-800 BAU/mL) and ultraresponders (Spike IgG titer > 800 BAU/mL), respectively. Among seronegative patients, two patients were negative also for cell mediated response, as tested with IFN-γ release Assay (IGRA) test. With a median of 85 days after the third dose, the median SARS-CoV-2 IgG titer was 1632 BAU/mL in 81 patients: only two patients were seronegative, whereas 16 and 63 patients were responders and ultraresponders, respectively. Among the 2 persistently seronegative patients, IGRA test was negative in one who had previously received anti-CD20 therapy. Documented paucisymptomatic (n = 3) or asymptomatic (n = 4) infection occurred after the third dose, during the Omicron wave., Conclusion: In patients treated with exclusive RT, even during the Omicron breakthrough, robust humoral response and clinical protection from severe SARS-CoV-2 disease were achievable with three doses of mRNA vaccine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: ERAS pathway has been proposed as the standard of care in elective abdominal surgery. Guidelines on ERAS in emergency surgery have been recently published; however, few evidences are still available in the literature. The aim of this study was to evaluate the feasibility of an enhanced recovery protocol in a large cohort of patients undergoing emergency surgery and to identify possible factors impacting postoperative protocol compliance., Methods: This is a prospective multicenter observational study including patients who underwent major emergency general surgery for either intra-abdominal infection or intestinal obstruction. The primary endpoint of the study is the adherence to ERAS postoperative protocol. Secondary endpoints are 30-day mortality and morbidity rates, and length of hospital stay., Results: A total of 589 patients were enrolled in the study, 256 (43.5%) of them underwent intestinal resection with anastomosis. Major complications occurred in 92 (15.6%) patients and 30-day mortality was 6.3%. Median adherence occurred on postoperative day (POD) 1 for naso-gastric tube removal, on POD 2 for mobilization and urinary catheter removal, and on POD 3 for oral intake and i.v. fluid suspension. Laparoscopy was significantly associated with adherence to postoperative protocol, whereas operative fluid infusion > 12 mL/Kg/h, preoperative hyperglycemia, presence of a drain, duration of surgery and major complications showed a negative association., Conclusions: The present study supports that an enhanced recovery protocol in emergency surgery is feasible and safe. Laparoscopy was associated with an earlier recovery, whereas preoperative hyperglycemia, fluid overload, and abdominal drain were associated with a delayed recovery., (© 2023. The Author(s).)

In this study we evaluated both~ K- and N- RAS mutations in plasma samples from patients with metastatic colorectal cancer by means of the BEAMing technology, and we assessed their diagnostic performance compared to RAS analyses performed on tissue. The sensitivity of BEAMing in identifying KRAS mutations was of 89.5%, with a fair specificity. The agreement with tissue analysis was moderate. The sensitivity for NRAS was high with a good specificity, and the agreement between tissue analysis and BEAMing was fair. Interestingly, significantly higher mutant allele fraction (MAF) levels were detected in patients with G2 tumors, liver metastases, and in those who did not receive surgery. NRAS MAF level was significantly higher in patients with mucinous adenocarcinoma and for those with lung metastases. A sharp increase in the MAF values was observed in patients who moved towards disease progression. More strikingly, molecular progression always anticipated the radiological one in these patients. These observations pave the way to the possibility of using liquid biopsy to monitor patients during treatment, and to enable oncologists to anticipate interventions compared to radiological analyses. This will allow time to be saved and ensure a better management of metastatic patients in the near future.

Purpose: The aim of this work is the development and characterization of a model observer (MO) based on convolutional neural networks (CNNs), trained to mimic human observers in image evaluation in terms of detection and localization of low-contrast objects in CT scans acquired on a reference phantom. The final goal is automatic image quality evaluation and CT protocol optimization to fulfill the ALARA principle., Approach: Preliminary work was carried out to collect localization confidence ratings of human observers for signal presence/absence from a dataset of 30,000 CT images acquired on a PolyMethyl MethAcrylate phantom containing inserts filled with iodinated contrast media at different concentrations. The collected data were used to generate the labels for the training of the artificial neural networks. We developed and compared two CNN architectures based respectively on Unet and MobileNetV2, specifically adapted to achieve the double tasks of classification and localization. The CNN evaluation was performed by computing the area under localization-ROC curve (LAUC) and accuracy metrics on the test dataset., Results: The mean of absolute percentage error between the LAUC of the human observer and MO was found to be below 5% for the most significative test data subsets. An elevated inter-rater agreement was achieved in terms of S-statistics and other common statistical indices., Conclusions: Very good agreement was measured between the human observer and MO, as well as between the performance of the two algorithms. Therefore, this work is highly supportive of the feasibility of employing CNN-MO combined with a specifically designed phantom for CT protocol optimization programs., (© 2023 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Background: Porocarcinoma (PC) is a rare cutaneous adnexal tumor with a variable metastatic potential. Given the paucity of data, guidelines and specific recommendations for PC are not yet well-established. In this study, we evaluate the disease-specific characteristics and outcome of this rare and often underestimated tumor., Materials and Method: A retrospective study of the epidemiological, clinical, and dermoscopic characteristics among cases of histopathologically diagnosed PC, collected from the database of two skin cancer clinics in Italy (Firenze, Pistoia) from 2000 to 2020, was conducted., Results: Among the 52 patients with 53 tumors, 31 were men (59.6%) and 21 were women (40.4%) with an age range of 49-96 years (median age 82 years). The most common locations were the head/neck region in men (34% in men vs. 17% in women) and the lower limb in women (17% in women vs. 9% in men). Forty-eight cases (91%) underwent local excision. Of these patients, two (4%) experienced local recurrence, and one (2%) developed a second PC on a different anatomical site 1 month after the primary tumor's excision. Lymph node metastases were present in three cases (6%). Two of them have been treated surgically with adjuvant radiotherapy (both are disease-free after a 2-year follow-up period), whereas the third case developed visceral metastases followed by PC-related death., Conclusions: This study, with 52 patients with 53 tumors covering a follow-up period of more than 5 years, shows a less aggressive behavior of PC with 4% local recurrence, 6% nodal metastases, and 2% mortality., (© 2022 the International Society of Dermatology.)

Objective: To compare one-year mortality risk associated with syncope and unexplained fall in older adults with dementia., Methods: 522 patients (aged >65 years) with dementia and history of transient loss of consciousness and/or unexplained falls were evaluated. The diagnosis of syncope was based on European Society of Cardiology guidelines. A "Syncopal Fall" was defined in patients with an initial clinical presentation of unexplained fall, but a final diagnosis of syncope after complete assessment. A "Truly Unexplained Fall" was defined in patients with an initial clinical presentation of unexplained fall, in whom a diagnosis of syncope had been excluded after the diagnostic work-up. One-year follow-up was assessed by phone interview., Results: Follow-up data were available for 501 participants (mean age 83 ± 6 years, 65% female). After a mean follow-up of 324 ± 93 days, death from any cause was reported in 188 participants (24%). Advanced age, male sex, cognitive and functional impairment were associated with a higher mortality rate. Patients with "Truly Unexplained Falls" had a higher mortality risk compared with syncope and "Syncopal Fall". A diagnosis of "Truly Unexplained Falls" remained an independent predictor of one-year all-cause mortality in multivariate model., Conclusions: We propose the novel diagnostic category of "Truly Unexplained Fall", resulting from the application of syncope guidelines to subjects with unexplained falls. This condition in older adults with dementia is a predictor of one-year all-cause mortality. For this new high risk profile, we advice a comprehensive geriatric assessment focused on risk factors for fall, aimed at a possible improvement of prognosis., (Copyright © 2022. Published by Elsevier B.V.)

Transmission with endoscopes, particularly duodenoscope, of potential lethal infections prompted different scientific societies to deliver recommendations aimed reducing this risk. Some International societies extended recommendations on microbial surveillance to all the endoscopes and devices used in the reprocessing procedure. Considering the relevance of the topic, 8 Italian scientific societies of physicians, nurses and technical operators prepared a concerted document taking into account Institutional advisories and facilities in Italy. The rules for a correct microbial surveillance on endoscopes were detailed in term of what, how and when to perform the procedure, also suggesting behaviors in case of contamination., Competing Interests: Declaration of Competing Interest none declared., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Study Objective: Several studies have been published on hysteroscopic treatment of cesarean scar defect using the 26 Fr resectoscope. This study compared the effects of the 26 Fr resectoscope with those of the 16 Fr mini-resectoscope in terms of efficacy, safety profile, and peri- and postoperative complications., Design: A prospective cohort study., Setting: Tertiary care university hospital (S. Orsola-Malpighi, Bologna, Italy)., Patients: Three hundred and nine women having symptoms and with a cesarean scar defect diagnosis were divided into 2 groups according to a temporal criterion: from March 2012 to March 2015, 155 consecutive women (control group) underwent isthmoplasty with the 26 Fr resectoscope (Karl Storz, Tuttlingen, Germany), whereas from April 2015 to March 2018, 154 consecutive women (study group) underwent isthmoplasty with the 16 Fr mini-resectoscope (Gubbini system, Tontarra Medizintechnik, Tuttlingen, Germany)., Interventions: One hundred and fifty-five women (control group) underwent isthmoplasty with the 26 Fr resectoscope, and 154 women (study group) underwent isthmoplasty with the 16 Fr mini-resectoscope. The so-called "channel-like" 360° endocervical resection technique was applied., Measurements and Main Results: The isthmoplasty time with the 2 resectoscopes, excluding cervical dilatation, was similar (p = .25), whereas the overall surgical time was shorter in the case of the mini-resectoscope. The use of the 16 Fr mini-resectoscope was significantly associated with a reduced volume of distension medium used (p <.001) and a lower fluid absorption (p <.001). A significant increase (p = .01) in postoperative complications in the control group (9/155; 5.8%) compared with the study group (1/154; 0.7%) was also found. No significant reduction in discharge time was observed between the 2 groups (p = .13). Patient satisfaction immediately after surgery was significantly higher (p <.001) in the study group than in the control group., Conclusion: Isthmoplasty with a 16 Fr mini-resectoscope seems to be as effective as isthmoplasty with a 26 Fr resectoscope in reducing postmenstrual abnormal uterine bleeding and suprapubic pelvic pain. It is associated with a significant reduction in overall surgical time owing to the non-necessity of performing cervical dilatation. The 16 Fr mini-resectoscope facilitates surgery in small anatomical spaces such as the cervical canal and reduces the complication rate linked to blind maneuvers not respecting the uterine anatomy., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

This corrects the article DOI: 10.23736/S0392-0488.17.05584-5.

Objectives: To evaluate the clinical characteristics and the long-term outcome of atrial fibrillation (AF) patients with dementia and history of syncope or falls., Design: Observational: analysis of a prospective registry., Setting and Participants: Between 2012 and 2016, the Syncope and Dementia Registry enrolled patients in 12 geriatric departments. Follow-up evaluation was at 12 months., Measures: Clinical, functional, and cognitive assessment., Results: Of the 522 patients (women, 62.1%; Mini-Mental State Examination 17 ± 6), 26.4% have or presented an AF history. Patients with AF were older (85 ± 6 vs 83 ± 6 years, P = .012), with higher heart rate (78 ± 17 vs. 73 ± 14 bpm, P < .001), prescribed drugs (6.9 ± 2.9 vs 5.9 ± 2.7, P < .001), and an increased number (3.9 ± 2.0 vs 3.0 ± 1.8, P < .001) and severity of comorbidities. Oral anticoagulant therapy was underprescribed (39.9%). Cardiac syncope was more frequently diagnosed (18.8 vs 4.9%, P < .001). At multivariate analysis, AF patients were characterized by advanced age, a higher severity of comorbidities, a greater number of prescribed drugs, an increased heart rate, and a more frequent presence of cardiac symptoms. One-year mortality differed little between patients with and without AF (27.7 vs 22.1%, P = .229). In the arrhythmia group, multivariate predictors of prognosis were disability (number of lost BADLs; P = .020) and a higher heart rate (P = .006)., Conclusions and Implications: AF and postural stability-related issues often co-exist in persons with dementia. This complex of conditions is associated with an intricate clinical picture, underprescription of oral anticoagulants, and high long-term mortality. Future studies are needed to evaluate the effects of therapy optimization in this population., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

The new corona virus disease has started in Wuhan - China at the end of 2019 and quickly spread with a pandemic trend across the rest of the world. The scientific community is making an extraordinary effort to study and control the situation, but the results are just partial. Based on the most recent scientific literature and strong statements by the most prestigious international health institutions, the Italian Society of Digestive Endoscopy has drawn up some recommendations about the use of personal protective equipment, the correct way of dressing and undressing of endoscopists and nurses, before and after digestive endoscopy procedures. In addition, some other important indications are given to reduce the risk of contamination of healthcare providers during endoscopic activities, in the setting of a pandemic. Nevertheless, because of the very quick evolution of our knowledge on this issue, these recommendations must be considered as evolving, because they could change in a short time., Competing Interests: Declaration of competing interest All the Authors declare that they have no conflict of interest., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The epidemiologic trends of cutaneous melanoma are similar in several countries with a Western-type lifestyle, where there is a progressively increasing incidence and a low but not decreasing mortality - even increasing in selected cases, especially in the older age groups. Also in Tuscany there is a steady rise in the incidence with prevalence of in situ and invasive thin melanomas, with also an increase of thick melanomas. It is necessary to reduce the frequency of thick melanomas to reduce specific mortality. The objective of the current survey has been to compare, in the Tuscany population, by a case-case study, thin and thick melanoma cases, trying to find out those personal and tumor characteristics which may help to customize preventive interventions., Methods: The study included nine centers involved in the melanoma diagnosis. A consecutive series of incident invasive melanomas diagnosed in a period of about 18 months (July 2010 to December 2011) was collected and matched according in a ratio of one thick melanoma (cutoff thickness: 1 mm) every two thin melanomas. The investigators filled in a questionnaire on patients' self-reported sun exposure, way of melanoma detection, awareness and performance of self-skin examination, as well as propensity to prevention in general., Results: The results of this survey confirm that older age and the lower education level are associated with a later detection. The habit of performing skin self-examination is crucial in the early diagnosis of thick melanoma. The results of this survey seem to suggest that population aged over 50 years, with few total and few atypical nevi, and limited sun exposure and burning are at higher risk of late diagnosis. It can be assumed that part of the population is not effectively reached by prevention campaigns because they do not recognize themselves as being at risk for skin cancers., Conclusions: In order to achieve a higher rate of early diagnosis of skin melanoma, a new strategy must be implemented. It could be useful to rethink educational campaigns - which seem to unintentionally leave out subjects more at risk for melanoma - and to renew the active involvement of the general practitioners.

Purpose: Laparoscopic peritoneal lavage (LPL) is feasible in selected patients with pelvic abscess and generalized purulent peritonitis caused by acute diverticulitis. We aimed to compare LPL and laparoscopic sigmoidectomy (LS) in complicated acute diverticulitis., Methods: This prospective, observational, multicenter study included patients with a pelvic abscess not amenable to conservative management and patients with Hinchey III acute diverticulitis, from 2015 to 2018. Sixty-six patients were enrolled: 28 (42%) underwent LPL and 38 (58%) underwent LS. In LS, patients had a primary anastomosis, with or without ileostomy, or an end colostomy (HA). Major outcomes were mortality, morbidity, failure of source control, reoperation, length of stay, and diverticulitis recurrence., Results: Patient demographics were similar in the two groups. In LPL, ASA score > 2 and Mannheim Peritonitis Index were significantly higher (p = 0.05 and 0.004). In LS, 24 patients (63%) had a PA and 14 (37%) an HA. No death was recorded. Overall, morbidity was 33% in LPL and 18% in LS (p = 0.169). However, failure to achieve source control of the peritoneal infection and the need to return to the operating room were more frequent in LPL (p = 0.002 and p = 0.006). Mean postoperative length of stay was comparable (p = 0.08). Diverticular recurrence was significantly higher in LPL (p = 0.003)., Conclusion: LPL is related to a higher reoperation rate, more frequent postoperative ongoing sepsis, and higher recurrence rates. Therefore, laparoscopic lavage for perforated diverticulitis carries a high risk of failure in daily practice.

Aims: Diabetic foot syndrome (DFS) increases the risk for atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or mortality. The present study aims at ascertaining whether such DFS-related excess risk differs between genders, retrospectively investigating a population with diabetes from Tuscany, Italy, followed-up for 6 years (2011-2016)., Methods: People with diabetes living in Tuscany on January 1st 2011 identified by administrative databases, were divided by baseline history of prior DFS hospitalizations, stratified by presence/absence of peripheral vascular disease and evaluating, by Cox regression analysis, whether adjusted DFS-related excess risk of incident ASCVD, CKD or mortality differed between genders., Results: In an overall population of 165,650 subjects with diabetes (81,829M/83,821F), basal prevalence of DFS was twice higher among males, who were moreover at a significantly greater risk of all considered outcomes along the 6-year period. On the contrary, baseline DFS significantly increased the hospitalization risk for ASCVD, CKD and mortality equally or at a slightly greater extent in females, while the risk for stroke was significantly associated with DFS only among females (HR: 1.622 (1.314-1.980); p = 0.0001 vs. HR: 1.132 (0.955-1.332); p = NS). This finding was even reinforced in non-vascular DFS, which was associated with a significant raised risk for stroke, heart failure or mortality exclusively in females., Conclusions: In this population, DFS prevalence and overall risk for ASCVD, CKD or mortality were significantly higher among males. Baseline co-presence of DFS, however, conferred a similar adjusted risk for all these outcomes between genders, and in case of non-vascular DFS the risk was significantly increased only among females.

Study Objective: To estimate the incidence of infection after diagnostic and operative hysteroscopic procedures performed in an in-office setting with different distension media (saline solution or CO 2 )., Design: Prospective, multicenter, observational study (Canadian Task Force classification II-2)., Setting: Tertiary women's health centers., Patients: A total of 42,934 women who underwent hysteroscopy between 2015 and 2017., Interventions: Of the 42,934 patients evaluated, 34,248 underwent a diagnostic intervention and 8686 underwent an operative intervention; 17,973 procedures used CO 2 and 24,961 used saline solution as a distension medium. Patients were contacted after the procedure to record postprocedure symptoms suggestive of infection, including 2 or more of the following signs occurring within the 3 weeks after hysteroscopy: fever; lower abdominal pain; uterine, adnexal, or cervical motion tenderness; purulent leukorrhea; vaginal discharge or itchiness; and dysuria. Vaginal culture, clinical evaluation, transvaginal ultrasound, and histological evaluation were completed to evaluate symptoms., Measurements and Main Results: Operative hysteroscopies comprised polypectomies (n = 7125; 82.0%), metroplasty (n = 731; 15.0%), myomectomy (n = 378; 7.8%), and tubal sterilization (n = 194; 4.0%). Twenty-five of the 42,934 patients (0.06%) exhibited symptoms of infection, including 24 patients (96%) with fever, 11 (45.8%) with fever as a single symptom, 7 (29.2%) with fever with pelvic pain, and 10 (41.7%) with fever with dysuria. In 5 patients with fever and pelvic pain, clinical examination and transvaginal ultrasound revealed monolateral or bilateral tubo-ovarian abscess. In these patients, histological examination from surgical specimens revealed the presence of endometriotic lesions., Conclusion: The present study suggests that routine antibiotic prophylaxis is not necessary before hysteroscopy because the prevalence of infections following in-office hysteroscopy is low (0.06%)., (Copyright © 2018 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Long QT and use of QT-prolonging drugs are common among older patients receiving polytherapies, but real-world evidence on their impact in clinical practice is controversial. We investigated prevalence, variables associated and clinical implications of prolonged corrected QT (QTc) among patients from the Syncope and Dementia study., Methods: Observational, prospective, multicenter study. Patients≥65 years with dementia and fall suspected for syncope in the previous three months were enrolled. Several clinical variables and the complete list of medications were recorded for each patient. A 12‑lead ECG was obtained and corrected QT was calculated by the Bazett's formula. One-year followup for death and recurrent syncope was performed., Results: Prolonged QTc was observed in 25% of the 432 enrolled patients (mean age 83.3), and was significantly associated with male gender (OR 2.09; 95% CI 1.34-3.26) and diuretics use (OR 1.85; 95% CI 1.18-2.90). At one-year 23.3% of patients died and 30.4% reported at least one recurrent event. Variables associated with one-year mortality were: age, male gender, atrial fibrillation (AF), use of calcium channel blockers and prolonged QTc (OR 1.80; 95% CI 1.01-3.20). Among patients with prolonged QTc a significant interaction for mortality was found with AF. Recurrent events were associated with the use of antiplatelets, cholinesterase. inhibitors and antipsychotics, but not with prolonged QTc., Conclusions: We documented a high prevalence of prolonged QTc, that was associated with male gender and diuretics but not with psychoactive medications. Patients with prolonged QTc had higher one-year mortality, that was four-fold increased in those with concomitant AF., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Aims: To investigate the different strategies adopted for the management of antithrombotic therapy and the related hemorrhagic and infective complication rates in patients undergoing cardiac implantable electronic devices (CIEDs) surgery in a real-world setting., Methods: THE Management of AntiThrOMbotic therApy in patients undergoing electrophysiological device surgery: Italian NatiOnal Multicenter Observational REgistry (HEMATOMA NO MORE) is an observational, prospective, multicenter, national cohort study (with a retrospective, multicenter, regional pilot phase) designed to enroll patients with standard indications to CIED implantations/replacements receiving concomitant antithrombotic therapy. The primary outcome is clinically significant pocket hematoma defined as a postprocedural hematoma, resulting in prolonged hospitalization and/or requiring interruption of antithrombotic therapy and/or requiring further surgery and/or requiring transfusion., Results: The pilot phase included 569 patients from 11 centers in Tuscany enrolled between September 2014 and May 2015 and followed up for 1 month. Patients were categorized according to the strategy of management of antithrombotic therapy, with heparin bridging being associated with the highest incidence of clinically significant pocket hematoma (12.3%). Overall nonpocket hemorrhagic events rate was quite low (0.52%) and thromboembolic complications were negligible (0.17%)., Conclusion: Occurrence of pocket hematoma in patients undergoing CIED surgery is largely influenced by the strategy of management of antithrombotic therapy. The HEMATOMA NO MORE will assess the impact of different strategies on the risk of developing pocket hematoma and of subsequent CIED-related infections.

Aims: To investigate whether statins reduce the risk to first hospitalization of bacterial infections, in patients with or without diabetes taking into account prior or incident comorbidities., Methods: By using administrative databases, the effect of current statin use was measured on the risk of first hospitalizations due to bacterial infections in people living in Tuscany, Italy, in the period January 1, 2011-December 31, 2015, after excluding those with previous statins use. Population was stratified as with (n = 128,207) or without diabetes (n = 3,304,906), and the hospitalization risk was analyzed by a Cox proportional hazards regression analysis after adjusting for age, gender, previous comorbidities, chronic renal failure, and prior or incident cardiovascular diseases., Results: During the 5-year follow-up, 31,543 hospitalizations for bacterial infections were observed: 2.08(2.06-2.10) per 1000 person-year in non-diabetic and 5679: 9.13(8.94-9.32) per 1000 person-year in diabetic population. Diabetes conferred a greater risk of hospitalizations, independently from confounders [adjusted HR (95% CI) 2.04 (1.97-2.10); P < 0.0001]. Statin use decreased the risk by about 2.5% for each one month of therapy, at the same extent in subjects with or without diabetes, after adjusting for all covariates., Conclusions: In this population, diabetes was associated by a twofold increase in the 5-year risk of hospitalizations for bacterial infections. Statin use decreased this risk to a same extent in subjects without or with diabetes, after adjusting for main confounders including comorbidities, and previous or incident cardiovascular events.

Objective: Women with diabetes have a greater excess risk for cardiovascular diseases (CVD) than men. This study was aimed at clarifying whether this effect is lifelong or more evident in some life-periods., Methods: The effect of diabetes and gender on the risk of first ever hospitalization for acute myocardial infarction (AMI), ischemic stroke (IS), congestive heart failure (CHF), lower extremity amputations (LEA) or any of these major cardiovascular events (MACE) have been evaluated by a Cox-hazard model, over years 2008-2012 querying administrative databases of a cohort living in Tuscany, Italy., Results: Comparing subjects with diabetes to those without it the overall age-adjusted excess risk was higher in women than in men for AMI and MACE and higher in men for LEA, with no difference for IS or CHF. In women the excess risk for AMI and MACE started earlier (46yr) and lasted until age of more than 85yr, while 'risk-windows' opened later and had a shorter duration for CHF (56-65yr) and IS (66-75yr)., Conclusion: Diabetic women have a significant diabetes-associated excess of CVD risk, except for LEA, with a 'risk window' opening earlier and lasting longer for AMI and MACE, later and with a shorter duration for IS and CHF., (Copyright © 2017 Elsevier Inc. All rights reserved.)

While in non-diabetic people the risk for cardiovascular disease is higher in men, diabetes completely reverts this sex-gender difference conferring to women a greater burden of cardiovascular complications. Additionally, all risk factors associated with cardiovascular disease appear to be more active in diabetic females than in their male counterparts. The reasons of this different impact of diabetes between genders are not completely clear. The aim of this review is trying to clarify these issues in a sex and gender perspective. Both genetic and hormonal factors are at the basis of sex-gender differences in diabetes, even do not explain the totality of data. Possibly women arrive later and in worse conditions to the diagnosis of diabetes, receive both diagnostic and therapeutic supports in a lesser measure and, finally, reach therapeutic goals as recommended by guidelines in a lesser extent. Further aspects of sex-gender differences in diabetic complications are represented by a more frequent prevalence of drug side effects in women, as well as by increased resistance to the action of drugs used in prevention or in the therapy of cardiovascular diseases. As to microvascular complications, the issue of sex-gender differences is even more complex, with some important differences emerging in experimental models 'in vitro', as well as in human pathology 'in vivo'. The main problem, however, also in this case, is that it is difficult to differentiate how common pathogenetic mechanisms acting in diabetes may differently impact between genders. In conclusion what is evident is that diabetes represents a 'risk magnifier' for the damage of both micro and macrovessels differently in men and in women. This issue deserves, therefore, a more careful approach from people involved in both clinical aspects and research regarding diabetes and its complications, in a sex-gender oriented perspective., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Variability in daily blood pressure (BPV) recorded 24-h ambulatory blood pressure monitoring (ABPM) is known to be related to left ventricular hypertrophy and an increased incidence of cardiovascular events in hypertensive patients. The aim of this study was to evaluate whether left atrium dimension, which increases early in hypertensive subjects, was related to BPV in a group of 167 drug-naive patients (100M/67F, age: 46±11yr). The patients were chosen among those consecutively sent by their general practitioners to confirm the existence of arterial hypertension and afterwards diagnosed as hypertensive (mean 24-h ABPM ⩾130/80 mm Hg). In each patient, the left atrial posteroanterior diameter index for height (LADi) and the left ventricular mass standardized for body surface area (LVMi) were measured using standardized echocardiographic methods. BPV was calculated as the weighted mean of daytime and nighttime systolic and diastolic blood pressure s.d.'s (ws.d.), according to the formula ws.d.=[(daytime s.d. × 10)+nighttime s.d. × 6)]/16. An increase in left atrial dimension (LADi>24 mm m(-1)) was present in 36 patients (21.6% of the total population). In a univariate regression, LVMi was significantly related to systolic BPV (r=0.24; P=0.02) only in men, whereas LADi was significantly related to both systolic and diastolic BPV in both genders. After adjusting for sex, age, BMI, heart rate, diastolic function and estimated glomerular filtration rate, both systolic and diastolic BPV remained significantly related to LADi (P=0.02 for both) but not to LVMi. In conclusion, this study suggests that BVP, as measured as BPws.d., is significantly and independently associated with increased LADi in newly diagnosed, treatment-naive hypertensive patients.

Background: To identify molecular biomarkers for tumor diagnosis and monitoring of disease progression, several noninvasive tests on liquid biopsy have been proposed for different cancers including those of urogenital origin. Among biomarkers, carbonic anhydrase IX (CAIX) has gained attention as it regulates extracellular pH and induces cytoplasmic alkalization contributing to malignant progression and poor treatment outcome. Works on tissues suggested the potential use of CAIX as a tumor biomarker for urogenital malignancies, but only few studies have been performed on its detection in urine., Scope: The aim of the present study is the measurement of CAIX messenger RNA (mRNA) in urine sediments of patients affected by kidney, prostate, and bladder cancers to evaluate the clinical sensitivity and specificity of the test., Procedures: The quantification of the total CAIX mRNA concentration and of its full-length isoform (CAIX FL) have been performed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) on RNA extracted from urine sediments of patients affected by urogenital cancers., Results: Urinary total CAIX mRNA expression resulted to be lower in patients with kidney and prostate cancer in comparison with the control group, but no statistically significant difference could be evidenced for bladder cancer. The evaluation of the relative percentage of FL isoform mRNA (FL%) showed a significant increase of FL% in urine from patients with cancer (median = 70.8%) in comparison with the healthy subjects (median = 2.6%) and this finding was confirmed for each cancer type separately. The comparison among receiver operating characteristic curves for total CAIX mRNA, CAIX FL mRNA, and FL% indicated that FL% shows the best diagnostic performance with 90% sensitivity and 72% specificity. Comparison of the results obtained in urine with those found in the corresponding tissues indicated 80% concordance., Conclusions: The CAIX mRNA expression in urine sediments can be considered a surrogate marker of CAIX expression in tumor tissues of urogenital origin. In particular, the analysis of FL% possesses the best characteristics to be a suitable noninvasive biomarker for urogenital cancer diagnosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Taurine transporter gene expression (RNA-TauT) has a role in retinal cell function and is modulated in vitro and in vivo by hyperglycemia and/or oxidative stress. This study was aimed at testing whether RNA-TauT gene expression is modified in blood mononuclear peripheral cells (MPCs) of type 1 diabetic patients, is related to plasma markers of oxidative stress or endothelial dysfunction, or, finally, is related to presence of retinopathy., Methods: RNA-TauT was measured in MPCs by real-time PCR-analysis in 35 type 1 diabetic patients and in 33 age- and sex-matched controls, additionally measuring plasma and cell taurine and markers of oxidative stress and endothelial dysfunction., Results: RNA-TauT, expressed as 2(-ΔΔCt), was significantly higher in MPCs of type 1 diabetic patients than in controls [median (interquartile range): 1.32(0.31) versus 1.00(0.15); P = 0.01]. In diabetic patients RNA-TauT was related to HbA1c (r = 0.42; P = 0.01) and inversely to plasma homocysteine (r = -0.39; P = 0.02) being additionally significantly higher in MPCs of patients without retinopathy [(n = 22); 1.36(0.34)] compared to those with retinopathy [(n = 13); 1.16(0.20)], independently from HbA1c or diabetes duration., Conclusions: RNA-TauT gene expression is significantly upregulated in MPCs of type 1 diabetes patients and is related to HbA1c levels and inversely to plasma homocysteine. Finally, in diabetes patients, RNA-TauT upregulation seems to be blunted in patients with retinopathy independently of their metabolic control or longer diabetes duration.