Predicting ventricular arrhythmia inducibility in ajmaline-induced Brugada type I pattern: Validation of the dST-Tiso interval.

INTRODUCTION: The dST-Tiso is a newly proposed electrocardiographic (ECG) marker during Brugada (BrS) type I pattern, that predicts the likelihood of ventricular arrhythmia (VA) inducibility in patients with ajmaline-induced pattern. The objective of this study was to validate the effectiveness of this criterion using an independent data set. METHODS: Consecutive patients exhibiting a BrS type I ECG pattern following ajmaline administration underwent programmed ventricular stimulation (PVS). dST-Tiso interval was measured in all patients and tested as a predictor for positive VA inducibility. RESULTS: Among 128 patients (median age 43 years, 59% male) with drug-induced BrS type I ECG pattern who underwent PVS, 32 (25.0%) had VA inducibility that required defibrillation. Compared to noninducible subjects, those with positive PVS were more commonly male (81% vs. 51%, p = 0.003), had longer PQ (165 vs. 160 ms, p = 0.016) and dST-Tiso (310 vs. 230 ms, p < 0.001) intervals, and shorter QT interval (412 vs. 420 ms, p = 0.022). When treated as a continuous variable, dST-Tiso confirmed significant association with VA inducibility, with an adjusted odds ratio of 1.02 (95% confidence interval: 1.01-1.03, p < 0.001) for each 1 ms increase in duration. A dST-Tiso interval >300 ms yielded a sensitivity of 75%, a specificity of 86%, and positive and negative predictive values of 69% and 91%, respectively. CONCLUSION: The validation of the model based on the dST-Tiso interval >300 ms confirmed its high accuracy in predicting VA inducibility in drug-induced BrS type I pattern. This straightforward ECG marker might be linked to the extent of the electrical substrate of the disease.

Temperature and ST-segment morphology remote monitoring: new perspectives for implantable cardiac monitors in Brugada syndrome.

INTRODUCTION: Patients with Brugada syndrome (BrS) face an increased risk of ventricular arrhythmias and sudden cardiac death. Implantable cardiac monitors (ICMs) have emerged as effective tools for detecting arrhythmias in BrS. Technological advancements, including temperature sensors and improved subcutaneous electrocardiogram (subECG) signal quality, hold promise for further enhancing their utility in this population. METHODS AND RESULTS: We present a case of a 40-year-old man exhibiting a BrS type 2 pattern on 12-lead ECG, who underwent ICM insertion (BIOMONITOR IIIm, BIOTRONIK) due to drug-induced BrS type 1 pattern and a history of syncope, with a negative response to programmed ventricular stimulation. The device contains an integrated temperature sensor and can transmit daily vital data, such as mean heart rate and physical activity. Several months later, remote alerts indicated a temperature increase, along with transmitted subECGs suggesting a fever-induced BrS type 1 pattern. The patient was promptly advised to commence antipyretic therapy. Over the following days, remotely monitored parameters showed decreases in mean temperature, physical activity, and mean heart rate, without further recurrence of abnormal subECGs. CONCLUSION: ICMs offer valuable insights beyond arrhythmia detection in BrS. Early detection of fever using embedded temperature sensors may improve patient management, while continuous subECG morphological analysis has the potential to enhance risk stratification in BrS patients.

Investigating Deep Sedation With Intravenous Ketamine in Spontaneous Respiration During Pulsed-Field Ablation.

OBJECTIVES: The authors report their experience of a protocol for deep sedation with ketamine in spontaneous respiration during the pulsed-field ablation (PFA) of atrial fibrillation (AF). DESIGN: Observational, prospective, nonrandomized fashion. SETTING: Single-center hospitalized patients. PARTICIPANTS: All consecutive patients undergoing PFA of AF. INTERVENTIONS: Patients undergoing deep sedation with intravenous ketamine. MEASUREMENTS AND MAIN RESULTS: The authors' sedation protocol involves the intravenous administration of fentanyl (1.5 µg/kg) and midazolam (2 mg) at low doses before local anesthesia with lidocaine. A ketamine adjunct (1 mg/kg) in 5-minute boluses was injected about 5 minutes before the first PFA delivery. The authors enrolled 117 patients (age = 59 ± 10 y, 74.4% males, body mass index = 27.6 ± 5 kg/m2, fluoroscopy time = 24 ± 14 minutes, skin-to-skin time = 80 ± 40 minutes and PFA LA dwell time = 24 ± 7 minutes). By the end of the procedure, pulmonary vein isolation had been achieved in all patients using PFA alone. The mean time under sedation was 54.9 ± 6 minutes, with 92 patients (79%) being sedated for <1 hour. A satisfactory Ramsay Sedation Scale level before ketamine administration was achieved in all patients, except one (80.3% of the patients with rank 3; 18.4% with rank 2). In all procedures, the satisfaction level was found acceptable by both the patient and the primary operator (satisfactory in 98.2% of cases). All patients achieved a Numeric Rating Scale for Pain ≤3 (none or mild). No major procedure or anesthesia-related complications were reported. CONCLUSION: The authors' standardized sedation protocol with the administration of drugs with rapid onset and pharmacologic offset at low doses was safe and effective, with an optimal degree of patient and operator satisfaction.

[Italian Cystic Fibrosis Registry (ICFR). Report 2021-2022]. / Registro Italiano Fibrosi Cistica (RIFC). Rapporto 2021-2022.

INTRODUCTION: Italian Cystic Fibrosis Registry (ICFR) collects data of patients with cystic fibrosis (CF) through the collaboration with Italian CF referral and support Centres (Italian law 548/93). It aims at analysing medium and long-term clinical and epidemiological trends, identifying healthcare needs at regional and national levels, contributing to healthcare programmes, and resource allocation. Italian data are also compared at international level through the collaboration with the European CF Registry for sharing epidemiological data on general aspects like CF epidemiology and specific topics such as the use of CFTR modulators. OBJECTIVES: The purpose of this Report is to provide updated demographic and clinical data of the Italian FC population for the years 2021 and 2022, to contribute essential information for the implementation of projects aimed at improving the management of patients affected by this disease. DESIGN: Analyses and results presented in this Report pertain to patients currently under care at Italian National Referral and Support Centres for Cystic Fibrosis and Paediatric Hospital 'Bambino Gesù' in the 2021-2022 period. Data were submitted by clinical Centres through a dedicated web-based software and underwent dual quality control (QC) measures: automated quantitative QC within the software and secondary QC at the European level before the integration into the European Cystic Fibrosis Registry. These measures ensure data completeness, accuracy, and longitudinal consistency with European core data. SETTING AND PARTICIPANTS: A total of 27 CF Centres, including referral and support centres, as well as 'Bambino Gesù' Children's Hospital CF centre, submitted their data to ICFR for the years 2021-2022. Althourgh CF Centres in Verona and Messina do not use the ICFR software, their data are centrally collected and subsequently forwarded to the European Registry. Data from service centres in Treviso and Rovereto are transmitted via the Verona CF Centre. Data from Sardinia Centre are currently unavailable. RESULTS: The results section provides a comprehensive overview of various aspects of CF epidemiology and patient characteristics. 1.Demography: in 2021 and 2022, 5,977 and 6,077 CF patients were respectively included in the ICFR, with median ages of 23.3 and 23.7 years. The prevalence rates were 10.1 and 10.3 per 100,000 residents in Italy for the respective years, with males comprising 51.6% on average. The distribution by age showed a higher frequency among patients aged 7 to 35 years; adult patients constituted 63.5% on average in both years. 2. Diagnosis: most CF patients were diagnosed before the age of two (mean value 57.9%), with a significant percentage diagnosed in adult age (35.4% in 2021 and 25.6% in 2022). 3.New diagnoses: there were 113 new diagnoses in 2021 and 121 in 2022, with estimated incidences of 1 in 9,097 living births in 2021 and 1 in 6,232 in 2022. 4. Genetics: genetic analyses were conducted on 99.9% of patients, revealing CFTR gene mutations in over 98% of cases. The F508del mutation was the most common (44% of alleles in 2021), with 18% of patients having at least one "residual function" mutation. Gating mutations were present in 3.4% of Italian patients, while 20% had at least one-stop codon mutation. 5.Lung function: lung function, measured by percent predicted (pp)FEV1 (Forced Expiratory Volume in the first second) progressively declined before adulthood, with the majority of paediatric patients (92.8% in 2021 and 93.8% in 2022) maintaining a ppFEV1≥70%. 6.Nutrition: critical periods for nutrition were identified as the first 6 months of life and adolescence, with higher prevalence of malnourished male adolescents compared to females. Suboptimal BMI values were more common in adult females (28.7% in 2021 and 26.9% in 2022) compared to males (14.2% in 2021 and 12.6% in 2022). 7. Complications: CF-related liver disease without cirrhosis was prevalent in patients under 18 years (21.9% in 2021 and 21.2 in 2022), while CF-related diabetes was most frequent in adults (24.2%). 8.Transplantation: over the two-year period, 28 patients underwent double-lung transplantation, with median ages of 29.1 in 2021 and 35.3 in 2022, respectively. Median waiting times ranged from 9.4 to 11.6 months. 9.Microbiology: chronic Pseudomonas aeruginosa infection affected 37.2% of adult patients in 2021 and 36.0% in 2022, compared to 7.4% and 6.5% in paediatric patients. Staphylococcus aureus infection rates were 34.6% and 42.2% in 2021 among adults and 34.4% and 36.7% in 2022 among paediatric patients. 10. Mortality: a total of 34 patients died during the 2021-22 period (19 females, 15 males), with median ages at death of 43.7 years in 2021 and 46 years in 2022 (excluding transplanted patients). CONCLUSIONS: The present Report is an update of the data published in the past years and summarizes the main epidemiological and clinical data regarding Italian CF subjects in the years 2021 and 2022. The number of patients registered in 2021 was 5,977, while in 2022 was 6,077. The population coverage estimates for 2022 to be around 97%. In 2020, 60.5% of patients were older than 18 years, in 2022 adult patients account for 63.5% of the Italian CF population. Over the years, therefore, an increase in the median age of Italian CF patients has been observed, reaching 23.7 years in 2022. The absolute number of new diagnoses per year remains substantially unchanged over the years (a total of 234 in the period under review). The median age at diagnosis in 2022 was 2.5 months, 62.6% of subjects are really diagnosed within the first year of life and almost 90% of them are diagnosed through neonatal screening. In 2022, almost all patients underwent genetic analysis (99.9%). Data collected confirm the great variability among Italian CF patients. As regards respiratory function, what is reported in previous reports is here confirmed, with an ever-increasing percentage of subjects under the age of 18 having normal respiratory function, moreover, less than 1% of paediatric patients has a severe lung function (ppFEV1<40). The marked improvement in this indicator in the adult population seems to be mainly due to the introduction from 2021 in Italy of therapy with highly effective CFTR modulators. At the same time, the close positive correlation between nutritional status and respiratory function is confirmed for the adult population. As regards chronic infection by Pseudomonas aeruginosa, in 2022, a reduction in the percentage of chronic infection is observed both among adults (36% vs 38.8% in 2020) and in paediatric patients (6.5% vs 7.6% in 2020). The most frequent complication in both paediatric and adult populations is liver disease (respectively, in 24.2% and 41.3% of subjects). In the two-year period, 34 patients died; their median age at death was between 43 and 46 years (transplant patients excluded); only two patients under the age of 18 died in the period 2021 and 2022, confirming once again that mortality in paediatric age is a rare event. The data presented in this Report shows how the register can be a national and international point of reference for CF patients and the scientific community, a tool for describing the Italian CF population over the years, and a starting point for planning epidemiological studies and clinical studies.

How to combine CTA, 99mTc-WBC SPECT/CT, and [18F]FDG PET/CT in patients with suspected abdominal vascular endograft infections?

PURPOSE: We aimed at comparing 99mTc-HMPAO white blood cells (99mTc-WBC) scintigraphy, 18fluorine-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) and CT angiography (CTA) in patients with suspected abdominal vascular graft or endograft infection (VGEI). Moreover, we attempted to define a new visual score for interpreting [18F]FDG PET/CT scans aiming at increasing its specificity. METHODS: We prospectively compared 99mTc-WBC SPECT/CT, [18F]FDG PET/CT, and CTA in 26 patients with suspected abdominal VGEI. WBC scans were performed and interpreted according to EANM recommendations. [18F]FDG PET/CT studies were assessed with both qualitative (Sah's scale and new visual score) and semi-quantitative analyses. CTA images were interpreted according to MAGIC criteria. Microbiology, histopathology or a clinical follow-up of at least 24 months were used to achieve final diagnosis. RESULTS: Eleven out of 26 patients were infected. [18F]FDG PET/CT showed 100% sensitivity and NPV, with both scoring systems, thus representing an efficient tool to rule out the infection. The use of a more detailed scoring system provided statistically higher specificity compared to the previous Sah's scale (p = 0.049). 99mTc-WBC SPECT/CT provided statistically higher specificity and PPV than [18F]FDG PET/CT, regardless the interpretation criteria used and it can be, therefore, used in early post-surgical phases or to confirm or rule out a PET/CT finding. CONCLUSIONS: After CTA, patients with suspected late VGEI should perform a [18F]FDG PET/CT given its high sensitivity and NPV. However, given its lower specificity, positive results should be confirmed with 99mTc-WBC scintigraphy. The use of a more detailed scoring system reduces the number of 99mTc-WBC scans needed after [18F]FDG PET/CT. Nevertheless, in suspected infections within 4 months from surgery, 99mTc-WBC SPECT/CT should be performed as second exam, due to its high accuracy in differentiating sterile inflammation from infection.

Laparoscopic posterior vaginal plication plus sacral colpopexy for severe posterior vaginal prolapse: A randomized clinical trial.

AIM: A randomized clinical trial proposing a new laparoscopic prosthetic and fascial approach to severe posterior vaginal prolapse. The primary endpoint was to evaluate the objective and subjective outcomes of our laparoscopic posterior plication (LPP) combined to "two-mesh" sacral colpopexy (laparoscopic sacral colpopexy [LSC]) in severe posterior vaginal prolapse, with a 1-year follow-up. The secondary endpoint was to evaluate the safety of this surgical procedure. METHODS: This is single-center prospective randomized double-blinded clinical trial. A total of 130 consecutive patients with anterior and/or apical pelvic organ prolapse (POP) (POP-Q stage ≥II) and severe posterior vaginal prolapse (posterior POP-Q stage ≥III) were prospectively assessed for inclusion into the study from November 2018 to January 2020. Patients underwent "two-meshes" LSC and were randomized in Group A (LSC plus LPP) and Group A (LSC alone). Of the 130 included subjects, 8 were excluded, not meeting inclusion criteria. Cure rate was evaluated objectively, using POP-Q study, and subjectively using PGI-I, POPDI-6, and FSDS questionnaires. Complications were assessed intra-, peri-, and postoperatively. Twelve-month follow-ups were analyzed for the study. RESULTS: We found in LSC plus LPP Group a significant improvement of Ap and genital hiatus POP-Q points. Our subjective study showed, at 12 months, a statistical difference in PGI-I successful outcomes rate in favor of LPP. Also the FSDS resulted significantly much more improved in Group A. We observed no statistical differences in terms of postoperative complications. CONCLUSIONS: Our LPP approach to LSC could be considered an effective and safe technique to POP patients with severe posterior prolapse.

Robot-assisted pelvic floor reconstructive surgery: an international Delphi study of expert users.

BACKGROUND: Robotic surgery has gained popularity for the reconstruction of pelvic floor defects. Nonetheless, there is no evidence that robot-assisted reconstructive surgery is either appropriate or superior to standard laparoscopy for the performance of pelvic floor reconstructive procedures or that it is sustainable. The aim of this project was to address the proper role of robotic pelvic floor reconstructive procedures using expert opinion. METHODS: We set up an international, multidisciplinary group of 26 experts to participate in a Delphi process on robotics as applied to pelvic floor reconstructive surgery. The group comprised urogynecologists, urologists, and colorectal surgeons with long-term experience in the performance of pelvic floor reconstructive procedures and with the use of the robot, who were identified primarily based on peer-reviewed publications. Two rounds of the Delphi process were conducted. The first included 63 statements pertaining to surgeons' characteristics, general questions, indications, surgical technique, and future-oriented questions. A second round including 20 statements was used to reassess those statements where borderline agreement was obtained during the first round. The final step consisted of a face-to-face meeting with all participants to present and discuss the results of the analysis. RESULTS: The 26 experts agreed that robotics is a suitable indication for pelvic floor reconstructive surgery because of the significant technical advantages that it confers relative to standard laparoscopy. Experts considered these advantages particularly important for the execution of complex reconstructive procedures, although the benefits can be found also during less challenging cases. The experts considered the robot safe and effective for pelvic floor reconstruction and generally thought that the additional costs are offset by the increased surgical efficacy. CONCLUSION: Robotics is a suitable choice for pelvic reconstruction, but this Delphi initiative calls for more research to objectively assess the specific settings where robotic surgery would provide the most benefit.

Is There a Role for Bladder Biopsy in the Diagnosis of Non-Hunner Lesions Interstitial Cystitis?

INTRODUCTION: Bladder pain syndrome/interstitial cystitis (BPS/IC) is either Hunner lesion interstitial cystitis (HL IC) or non-Hunner lesion interstitial cystitis (N-HL IC), differing in the presence of HLs on cystoscopy. Cystoscopy is essential in diagnosing HL but are bladder biopsies useful in N-HL IC patients? Our objective was to assess bladder biopsy in patients with N-HL IC, evaluating whether the count of mast cells (MCs) and percentage of activated MCs could measure severity. MATERIALS AND METHODS: This is a single-centre retrospective study. INCLUSION CRITERIA: diagnosis of BPS/IC by ESSIC definition; absence of HLs. Each patient had three bladder biopsies. STATISTICAL ANALYSIS: χ2/Fischer's exact test; Wilcoxon signed-ranks test/Mann-Whitney U test. Statistical significance: p < 0.05. RESULTS: We separated 48 women into Group 1 with <50% of MCs activated and Group 2 with >50%. We compared the results of the O'Leary-Sant questionnaire between the two groups and did not find any correlation between the severity of the pathology and either the MC count in the detrusor or the percentage of activated MCs in the lamina propria or detrusor. DISCUSSION/CONCLUSION: These findings cast doubt on the usefulness of bladder biopsy for the evaluation of severity in N-HL IC.

Lymphopenia in patients affected by SARS-CoV-2 infection is caused by margination of lymphocytes in large bowel: an [18F]FDG PET/CT study.

BACKGROUND: To investigate the cause of lymphopenia in patients with newly diagnosed COVID-19, we measured [18F]FDG uptake in several tissues, including the ileum, right colon, and caecum at diagnosis and after recovery and correlated these measurements with haematological parameters. METHODS: We studied, by [18F]FDG PET/CT, 18 newly diagnosed patients with COVID-19. Regions of interest were drawn over major organs and in the terminal ileum, caecum, and right colon, where the bowel wall was evaluable. Five patients were re-examined after recovery, and three of them also performed a white blood cell scan with 99mTc-HMPAO-WBC on both occasions. Complete blood count was performed on both occasions, and peripheral blood lymphocyte subsets were measured at diagnosis. Data were analysed by a statistician. RESULTS: Patients had moderate severity COVID-19 syndrome. Basal [18F]FDG PET/CT showed focal lung uptake corresponding to hyperdense areas at CT. We also found high spleen, ileal, caecal, and colonic activity as compared to 18 control subjects. At recovery, hypermetabolic tissues tended to normalize, but activity in the caecum remained higher than in controls. Regression analyses showed an inverse correlation between CD4 + lymphocytes and [18F]FDG uptake in the caecum and colon and a direct correlation between CD8 + lymphocytes and [18F]FDG uptake in lungs and bone marrow. WBC scans showed the presence of leukocytes in the caecum and colon that disappeared at recovery. CONCLUSIONS: These findings indicate that lymphopenia in COVID-19 patients is associated with large bowel inflammation supporting the hypothesis that CD4 + lymphocytes migrate to peripheral lymphoid tissues in the bowel.

Transobturator tape versus single incision sling: how are they different? Clinical outcomes and ultrasonographic features of two mid-urethral slings.

PURPOSE: Stress urinary incontinence (SUI) is usually treated with mid-urethral slings. The best approach is still debated and the relationship between slings and pelvic structures is not completely understood. The aim of this study is to identify any difference between trans-obturator tape (TOT) and single incision sling (minisling). METHODS: Patients submitted to TOT or minisling were included in the study. Q-tip and stress test, ICIQ-SF questionnaire, PGI-I validated score, and 2D/3D transvaginal ultrasound parameters were collected at 1- and 6-month follow-up. Correlations between ultrasound parameters and clinical outcomes, PGI-I and ICIq-SF, were performed. RESULTS: 61 patients were included in the study. PGI-I score was significantly lower in the minisling group than in TOT group at 1-month (p = 0.016) and 6-month follow-up (p = 0.076). The median distance between the sling and the lumen of urethra was significantly higher and the angle between the branches of the sling was significantly narrower in the minisling group. There were significant differences in distances between the sling and the bladder neck at 1-month and 6-month follow-up. An inverse correlation between angle of the branches and the Q-tip test was observed (p = 0.059 Pearson's Rho - 0.578). PGI-I correlated also with angle of the branches (p = 0.009, Pearson's Rho 0.503). CONCLUSION: Patients undergoing TOT or minisling are similarly satisfied but show differences at ultrasound exam at 1- and 6-month follow-up. Pelvic floor ultrasound could be used in a short-term follow-up to visualize the sling position and to plan the most appropriate follow-up strategy.

Laparoscopic sacral hysteropexy versus laparoscopic sacral colpopexy plus supracervical hysterectomy in patients with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The choice of whether or not to preserve the uterus in the case of patients with urogenital prolapse who undergo sacral colpopexy is still debated. We compared objective and subjective outcomes of laparoscopic sacral hysteropexy (LSHP) and laparoscopic sacral colpopexy with concomitant supracervical hysterectomy (LSCP/SCH) in patients with symptomatic pelvic organ prolapse. METHODS: This is a multicenter retrospective cohort study conducted at the Urogynecology Department of the Fondazione Policlinico Universitario A. Gemelli IRCCS of Rome and at the Diaconesses Croix Saint Simon Hospital of Paris. We collected data of 136 patients; 78 underwent LSHP and 58 underwent LSCP/SCH for pelvic organ prolapse between January 2016 and December 2017. RESULTS: Patients of the two groups had similar preoperative characteristics. All patients completed 24-month follow-up evaluation. Overall, anatomical cure rate was 84.6% and 87.9% in the LSHP group and LSCP/SCH group, respectively, without statistically significant differences. In particular, in the LSHP group the anatomical success rate was 94.9%, 92.3% and 92.3% for the apical, anterior and posterior vaginal compartment whereas in the LSHP group LSCP/SCH was 100%, 91.4% and 94.8%, respectively. Subjective success rate was 89.7% among patients who underwent LSHP and 93.1% among women who underwent LSCP/SCH (p = 0.494). The median operative time (OT) was significantly shorter in LSHP. There were no significant differences between the groups in terms of estimated blood loss, conversion to laparotomy and intra- and postoperative complications. Patients' satisfaction was high in both groups without statistical differences. CONCLUSIONS: Both laparoscopic procedures are safe and effective in the treatment of pelvic organ prolapse. LSHP can be offered as an alternative in women who are strongly motivated to preserve the uterus in the absence of abnormal uterine findings.

Laparoscopic ventral rectopexy plus sacral colpopexy: continuous locked suture for mesh fixation. A randomized clinical trial.

PURPOSE: Laparoscopic ventral rectopexy (LVR) plus sacral colpopexy (LSC) is a high-complexity surgical procedure. The aim of the present study was to evaluate a new approach to rectal-mesh fixation during LVR with continuous locked suture. METHODS: This is a prospective randomized double-blinded clinical trial enrolling 80 patients with severe POP and obstructed defecation syndrome (ODS) from November 2016 to January 2021. Patients underwent a "two-meshes" LSC plus LVR and were randomized, regarding rectal mesh fixation, in Group A (extracorporeal interrupted 0 delayed absorbable sutures) and Group B ("U-shaped" running locked 0 delayed absorbable suture). Our primary endpoints were the operative times (OT); the secondary endpoints were the incidence of anatomical failures, vaginal mesh erosions and surgical complications. RESULTS: A total of 75 patients completed the study. Baseline characteristics were similar between the groups. Overall OT (156 vs 138 min; p < 0.05; treatment reduction of 11.5%) and LVR mesh fixation time (29 vs 16 min; p < 0.05; treatment reduction of 44%), resulted in significantly lower in Group B. No differences were found in terms of anatomic failure, vaginal mesh erosion or intra- or post-operative complications. PGI-I, FSDS and Wexner questionnaires resulted significantly improved after surgery, without statistical differences between the studied surgical procedures. CONCLUSION: Laparoscopic continuous locked 0 absorbable suture for LVR mesh fixation guaranteed a faster and effective alternative to multiple interrupted sutures. The significant OT reduction linked to this technique should be considered even more helpful when performing a highly complex surgery such as LVR. CLINICAL TRIAL REGISTRATION: NCT05254860 (13/02/2017).

[Italian Cystic Fibrosis Registry (ICFR). Report 2019-2020]. / Registro italiano Fibrosi Cistica (RIFC). Rapporto 2019-2020.

INTRODUCTION: Italian cystic fibrosis registry (ICFR) collects data from cystic fibrosis (CF) patients through the collaboration with Italian CF referral and support Centres (Italian law 548/93). ICFR contributes: • to the analysis of medium and long term clinical and epidemiological trends of the disease; • to the identification of the main health care needs at regional and national level to contribute to the Health Care programmes and to the distribution of resources; • to the comparison of the Italian data with international ones. This latter is based on the collaboration with the European CF registry and, due the COVID-19 pandemic emergency, with important global projects. OBJECTIVES: The purpose of this Report is to update the demographic and clinical data of the Italian FC population in the years 2019 and 2020, contributing to the information necessary to implement projects to improve the management of patients affected by this disease. DESIGN: Analyses and results described in the present Report are referred to patients currently followed at the Italian National Referral and Support Centres for Cystic Fibrosis in the 2019-2020 period. Data were sent by clinical Centres through a dedicated web-based software. Data undergo a double quality control (QC): the first is automatically performed by the software (quantitative QC), the second is performed at a European level (before the inclusion of the Italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and the accuracy of data as well as their longitudinal consistency with the European core data. SETTING AND PARTICIPANTS: A total of 29 CF Centres (referral and support centres and 'Bambino Gesù' Children's Hospital CF centre) sent to ICFR their data referred referred to years 2019-2020. CF Centres of Verona, Messina, and Palermo (this latter only for 2019) do not use the ICFR software; however, their data are firstly collected in a centralized manner, then sent to the European Registry. Data from support centres of Treviso and Rovereto are sent through the Verona CF Center. Finally, data from Sardinia Centre are still missing. RESULTS: The present Report has been organized into 10 sections. 1. Demography: in 2019, 5,585 CF patients were registered in the ICFR and 5,801 in 2020; median age was 21.6 years in 2019 and 22.4 years in 2020. Prevalence was 9.36/100,000 and 9.79/100,000 residents in Italy in 2019 and in 2020, respectively. Male percentage was 51.5% in 2019 and 2020 and CF distribution by age range showed higher frequency in patients aged 7 to 35 years. Adult patients (aged more than 18 years) were 59.5% on average in both years. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (median value 68.5%); a significant percentage of patients (12.9% in 2019 and 13.4% in 2020) was diagnosed in adult age. 3. New diagnoses: new diagnoses were 136 in 2019 and 96 in 2020. Estimated incidence was 1/5.568 living births in 2019 and 1/7.369 in 2020. 4. Genetics: 99.9% of patients underwent genetic analyses and in 98.2% of these patients a mutation in Cystic Fibrosis Transmembrane Regulator (CFTR) gene was identified. The F508del mutation was the most frequent (identified in 44.7% allele; 2019 data). Furthermore, on average 17.3% of patients had at least one 'residual function' mutation. At least one gating mutation is present in 3.3% of Italian patients. Finally, 20.5% of patients had at least one stop codon mutation (class 1). 5. Lung function: percent predicted FEV1 (Forced Expiratory Volume in the first second) progressively declined before adult age, in accordance with the natural history of the disease. The majority of paediatric patients (6-17 years of age), i.e., 86.7% in 2019 and 90.5% in 2020, had percent predicted FEV1 >=70%; whereas paediatric patients with a FEV1% >=40% are less than 2% in the study period. 6. Nutrition: the two most critical periods are the first 6 months of life and adolescence. Prevalence of malnourished adolescent males (12-17 years of age) is higher than the prevalence observed in females. Increasing percentages of female patients with a suboptimal BMI value (33.5% and 31.4%, respectively, in 2019 and 2020) are observed in adult age. 7. Complications: in 2019, CF-related liver disease without cirrhosis was the main complication both in patients aged less than 18 years (20.3% on average) and in adults (37.5%). CF-related diabetes was also frequent in CF adults (23.4%). 8. Transplantation: in 2019-2020, 64 patients received a double-lung transplantation. Median and range of age were 33 years (12.29-57.46) in 2017 and 32.9 (16.5-53.6) years in 2020. Median waiting times for lung transplantation in the two-year period ranged from 6 to 8 months. 9. Microbiology: percentage of adult patients with chronic Pseudomonas aeruginosa infection was 41.6% in 2019 and 38.8% in 2020 vs 14.3% in 2019 and 7.6% in 2020 in paediatric age. Staphylococcus aureus infection is present in 31.1% and 35.9% of adult patients in 2019 and in 33.5% and 34.7% of paediatric patients in 2020. 10. Mortality: a total of 51 patients died in the 2019-2020 period (28 females and 23 males); median age at death was 35.7 years in 2019 and 39 years in 2020 (transplanted patients are not included). CONCLUSIONS: The present report shows that the Italian CF population is growing (4,159 in 2010 vs 5,801 in 2020). Median age of patients increased in the 2010-2020 period (17 years in 2010 vs 22.4 years in 2020). Prevalence of adult patients is increasing (in 2020, 60.5% of patients is more than 18 years old). About 68.5% of new patients is diagnosed within the second year of life and median age at death (transplanted patients not included) increased in 2020 up to 39 years (in 2018 this value was 35.8). Some statistical differences between 2019 and 2020 are mainly due to the absence of about 200 patients not included in 2019 data by a participating centre for a technical problem.

Neck circumference as reliable predictor of mechanical ventilation support in adult inpatients with COVID-19: A multicentric prospective evaluation.

AIMS: COVID-19 is especially severe for elderly subjects with cardiometabolic and respiratory comorbidities. Neck circumference (NC) has been shown to be strongly related to cardiometabolic and respiratory illnesses even after adjustment for body mass index (BMI). We performed a prospective study to investigate the potential of NC to predict the need for invasive mechanical ventilation (IMV) in adult COVID-19 inpatients. MATERIALS AND METHODS: We prospectively and consecutively enrolled COVID-19 adult patients admitted to dedicated medical wards of two Italian hospitals from 25 March to 7 April 2020. On admission, clinical, biochemical and anthropometric data, including BMI and NC were collected. As primary outcome measure, the maximum respiratory support received was evaluated. Follow-up time was 30 days from hospital admission. RESULTS: We enrolled 132 subjects (55.0-75.8 years, 32% female). During the study period, 26 (19.7%) patients underwent IMV. In multivariable logistic regression analyses, after adjusting for age, sex, diabetes, hypertension and COPD, NC resulted independently and significantly associated with IMV risk (adjusted OR 1.260-per 1 cm increase 95% CI:1.120-1.417; P < .001), with a stronger association in the subgroup with BMI ≤30 Kg/m2 (adjusted OR 1.526; 95% CI:1.243-1.874; P < .001). NC showed a good discrimination power in predicting patients requiring IMV (AUC 0.783; 95% CI:0.684-0.882; P < .001). In particular, NC > 40.5 cm (>37.5 for females and >42.5 for males) showed a higher and earlier IMV risk compared to subjects with lower NC (Log-rank test: P < .001). CONCLUSIONS: NC is an easy to measure parameter able to predict the need for IMV in adult COVID-19 inpatients.

Perinatal outcomes in women with cystic fibrosis: Data from the Italian Cystic Fibrosis Registry.

INTRODUCTION: Data from the Italian Cystic Fibrosis Registry concerning pregnancies in the period 2010-2015 were used to investigate the association between the preconception clinical status and perinatal outcomes of women with cystic fibrosis (CF). MATERIAL AND METHODS: The assessed clinical variables were genotype, age at the time of conception, body mass index (BMI) and the percentage of predicted forced expiratory volume in the first second (ppFEV1 ). The analyzed outcomes were gestational age, birthweight and the frequency of cesarean deliveries. A generalized linear mixed model (GLIMMIX) was used to evaluate the association between type of delivery and age at the time of becoming pregnant, BMI, ppFEV1 and gestational age. Robust multivariable regression was used to evaluate the relation between gestational age and age at the time of becoming pregnant, BMI and ppFEV1 . Multivariable linear regression was performed to verify association between birthweight and BMI, and ppFEV1 . RESULTS: Complete information concerning mother and child was available for 56 completed pregnancies. Median age at the time of conception was 30.8 years (range: 18.7-42.3); median BMI was 21.5 kg/m2 (range: 16.5-26.8); and median ppFEV1 was 73.9 (range: 30-128). In all, 31 women (55.36%) had a genotype consisting of two CF-causing variants. Eight were homozygous for the F508del mutation (14.28% of the total). The median duration of pregnancy was 37 weeks (range: 31-41) and the frequency of prematurity (<37 weeks of gestational age) was 28.30%. Median birthweight was 2910 g (range: 1300-3650). The overall frequency of cesarean sections was 63.64%. A low preconception ppFEV1 was associated with prematurity (p = 0.014), and birthweight was positively related to ppFEV1 (p = 0.04). There was no association between the clinical variables or gestational age and the type of delivery. CONCLUSIONS: Maternal preconceptional respiratory function correlates with the duration of pregnancy and the birthweight of newborns. Cesarean deliveries are also frequent among young women with CF with normal respiratory function.

Extensive Histopathological Characterization of Inflamed Bowel in the Dextran Sulfate Sodium Mouse Model with Emphasis on Clinically Relevant Biomarkers and Targets for Drug Development.

This study aims to develop a reliable and reproducible inflammatory bowel disease (IBD) murine model based on a careful spatial-temporal histological characterization. Secondary aims included extensive preclinical studies focused on the in situ expression of clinically relevant biomarkers and targets involved in IBD. C57BL/6 female mice were used to establish the IBD model. Colitis was induced by the oral administration of 2% Dextran Sulfate Sodium (DSS) for 5 days, followed by 2, 4 or 9 days of water. Histological analysis was performed by sectioning the whole colon into rings of 5 mm each. Immunohistochemical analyses were performed for molecular targets of interest for monitoring disease activity, treatment response and predicting outcome. Data reported here allowed us to develop an original scoring method useful as a tool for the histological assessment of preclinical models of DSS-induced IBD. Immunohistochemical data showed a significant increase in TNF-α, α4ß7, VEGFRII, GR-1, CD25, CD3 and IL-12p40 expression in DSS mice if compared to controls. No difference was observed for IL-17, IL-23R, IL-36R or F480. Knowledge of the spatial-temporal pattern distribution of the pathological lesions of a well-characterized disease model lays the foundation for the study of the tissue expression of meaningful predictive biomarkers, thereby improving translational success rates of preclinical studies for a personalized management of IBD patients.

[Italian Cystic Fibrosis Registry (ICFR). Report 2017-2018]. / Registro italiano Fibrosi Cistica (RIFC). Rapporto 2017-2018.

INTRODUCTION: On the 15th of November 2020, the National Centre for Rare Diseases of the Italian National Health Institute, clinicians of the Italian National Referral and Support Centres for Cystic Fibrosis, Children's Hospital "Bambino Gesù", Italian Cystic Fibrosis Society, Italian League for Cystic Fibrosis renewed the agreement about CF data flow for a 3-year period. The possibility to access data by third parties is among the most important innovation introduced within the agreement. OBJECTIVES: Aim of the present Report is to improve the know-how of cystic fibrosis (CF) through a better characterization of Italian patients. Furthermore, the present Report aims at improving the care of CF patient. In particular, this Report should contribute to the following objectives: • to analyse the medium- and long-term clinical and epidemiological trends of the disease; • to identify the main healthcare needs at regional and national level, in order to contribute to the healthcare programmes and to the distribution of resources; • to compare Italian data with international ones. DESIGN: Analyses and results described in the present Report are referred to patients currently followed at the Italian National Referral and Support Centres for Cystic Fibrosis in the 2017-2018 period. Data were sent by clinical Centres through a new-committed software. Data underwent a double quality control (QC): the first is automatically performed by the software (quantitative QC), the second is performed at a European level (before the inclusion of the Italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and the accuracy of data as well as their consistency with the European core data. SETTING AND PARTICIPANTS: The present Report has been organized into 10 sections. 1. Demography: in the ICFR, 5,565 CF patients were registered in 2017 and 5,501 in 2018; median age was 21.4 years in 2017 and 21.2 years in 2018. Prevalence was 9.20/100,000 residents in Italy in 2017 and in 2018. Male percentage was 51.65% in 2017 and 2018, CF distribution by age range showed higher frequency in patients aged 7 to 35 years. Adult patients (aged more than 18 years) were 56.4% on average in 2017 and 2018. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (median value 66.4%); a significant percentage of patients (21.6% in 2017 and 18.3% in 2018) was diagnosed in adult age. 3. New diagnoses: new diagnoses were 162 in 2017 and 142 in 2018. Estimated incidence was 1/5.214 living births in 2017 and 1/5.442 in 2018. 4. Genetics: 99.8% of patients underwent genetic analyses and in 97.1% of these patients a mutation in Cystic Fibrosis Transmembrane Regulator (CFTR) gene was identified. The F508del mutation was the most frequent (44.6% in 2018). Furthermore, 16.3% of patients in 2017 and 16.9% of patients in 2018 had at least one 'residual function' mutation. At least one gating mutation is present in 3.3% of Italian patients. Finally, 20.5% of patients had at least one stop codon mutation (class 1). 5. Lung function: percent predicted FEV1 (Forced Expiratory Volume in the first second) progressively declined before adult age, in accordance with the natural history of the disease. The majority of paediatric patients (6-17 years of age), i.e., 86.70% in 2017 and 90.50% in 2018, had percent predicted FEV1 ≥70%; whereas paediatric patients with a FEV1% ≤40% are less than 2% in the 2017-2018 period. 6. Nutrition: the two most critical periods are the first 6 months of life and adolescence. Prevalence of malnourished adolescent males (12-17 years of age) is higher than the prevalence observed in females. Increasing percentages of adult female patients with a suboptimal BMI value (39.1% and 36.1%, respectively, in 2017 and 2018) are observed. 7. in 2018, CF-related liver disease without cirrhosis was the main complication both in patients aged less than 18 years (17.0% on average) and in adults (31.5%). CF-related diabetes was also frequent in CF adults (23.4%). 8. Transplantation: in 2017-2018, 83 patients received a double-lung transplantation. Median and range of age were 29.3 years (11.8-60.2) in 2017 and 29.1 (7.8-45.6) years in 2018. Median waiting times for lung transplantation in the two considered years were 8.6 and 7.7, respectively. 9. Microbiology: percentage of adult patients with chronic Pseudomonas aeruginosa infection was 51.3% in 2017 and 46.3% in 2018 vs 15.6% in 2017 and 10.2% in 2018 in paediatric age. Staphylococcus aureus infection is present in 53.4% and 53.5% of adult patients in 2017 and in 41.6% and 37.5% of paediatric patients in 2018. 10. Mortality: a total of 89 patients died in the 2017-2018 period (49 females); median age at death was 33.9 years in 2017 and 35.8 years in 2018 (transplanted patients are not included). CONCLUSIONS: The present report shows that the Italian CF population is growing (4,159 in 2010 vs 5,501 in 2018; +1,342). Quality of data collected has been improved by the drastic reduction of missing data, thanks to the new software for data collection. Median age of patients increased in the 2010-2018 period (17 years in 2010 vs 21.2 years in 2018). Paediatric death is a very rare event. A very low percentage of paediatric population was characterized by severe lung disease (FEV1% <40). Prevalence of adult patients is increasing (56.4% in 2018). Age at diagnosis is decreasing (4.2 months in 2017 vs 3.8 months in 2018). Median age at death (transplanted patients not included) was 33.9 in 2017 and 35.8 in 2018. RIFC is completely compliant with the GDPR (UE 2016/679 regulation) and its role in national and international CF communities is confirmed.

Titanized polypropylene mesh in laparoscopic sacral colpopexy.

INTRODUCTION: This study investigated perioperative and mid-term clinical outcomes after laparoscopic sacrocolpopexy (LSCP) with light titanium-coated polypropylene (TCP) mesh in a large group of patients affected by International Continence Society stage II-IV pelvic organ prolapse (POP). METHODS: This multicenter retrospective study included 217 patients treated with LSCP using TCP mesh. We aimed to (1) analyze the intra- and postoperative complication rates according to the ICS/IUGA Complication Classification Code guidelines, (2) evaluate the anatomical results and (3) assess postoperative patient satisfaction with the Patient Global Impression Improvement questionnaire. Nonparametric Wilcoxon signed-rank tests, χ2 test and Fisher's exact test were used where appropriate. RESULTS: The intraoperative complications were two (0.9%) cases of hemorrhage, two (0.9%) cases of incidental cystotomy and four (1.8%) cases of incidental colpotomy. During the postoperative follow-up, we recorded mesh exposure in 3 (1.4%) out of 217 patients. These 3 patients were from a group of 22 women who underwent vaginal opening during surgery, while in the remaining 195 patients without incidental colpotomy, no mesh exposure was observed (13.6% vs. 0.0%, p < 0.001). No failure of the apical compartment was observed, while 3 (1.4%) out of 217 patients experienced isolated anterior recurrence, and 1 (0.4%) patient had isolated posterior recurrence. All patients reported PGI-I scores ≥ 3, and 209 patients (96.3%) had a PGI-I score ≥ 2. CONCLUSIONS: The use of light TCP mesh is safe and effective during LSCP for POP repair from both an anatomical and a functional point of view, posing a very low postoperative mesh-related complication risk.

Effects of Citicoline, Homotaurine, and Vitamin E on Contrast Sensitivity and Visual-Related Quality of Life in Patients with Primary Open-Angle Glaucoma: A Preliminary Study.

The aim of the present study was to evaluate the effects of supplementation with a fixed combination of citicoline 500 mg, homotaurine 50 mg, and vitamin E 12 mg (CIT/HOMO/VITE) on contrast sensitivity and visual-related quality of life in patients with primary open-angle glaucoma (POAG) in mild stage. This was a multicenter, observational, cross-over, short-term, pilot study on POAG patients with stable controlled intraocular pressure (IOP). Patients were randomly assigned to Group 1 (current topical therapy for 4 months and then current topical therapy plus CIT/HOMO/VITE for 4 months) or Group 2 (CIT/HOMO/VITE in addition to current topical therapy for 4 months and then topical therapy alone for 4 months). Best-corrected visual acuity, IOP, visual field, and the Spaeth/Richman contrast sensitivity (SPARCS) test score were recorded at baseline and after 4 and 8 months. The Glaucoma Quality of Life-15 (GQL-15) questionnaire was administered at each check time. Forty-four patients were assigned to Group 1 and 65 to Group 2. Over the follow-up period, there were no significant changes in IOP or visual field findings, whereas SPARCS and GQL-15 findings significantly varied from baseline, both being improved in subjects treated with CIT/HOMO/VITE fixed combination. These results demonstrate that a daily intake of a fixed combination of citicoline, homotaurine, and vitamin E in addition to the topical medical treatment significantly increased the total score of the contrast sensitivity test and the quality of life in patients with POAG.

Sclerostin is expressed in the atherosclerotic plaques of patients who undergoing carotid endarterectomy.

BACKGROUND: Sclerostin (SC) is a monomeric glycoprotein expressed by osteocytes that affects bone formation. Recent studies have suggested a potential role for this protein in the pathophysiology of vascular diseases. The aim of the present study was to investigate SC expression in atherosclerotic plaques of patients affected by severe atherosclerotic disease who underwent carotid endarterectomy. We also evaluated possible differences in SC expression between patients with and without type 2 diabetes (T2D). METHODS: This was a cross-sectional study involving 46 patients aged 55 to 80 years (mean, 71.1 ± 6.7 years, 36 men, 15 patients with T2D) who underwent carotid endarterectomy. Immunohistochemical levels of SC were evaluated in the atherosclerotic plaques by double-staining immunochemistry, and serum SC levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: Sclerostin was present in the atherosclerotic plaques of all subjects investigated and increased significantly in the media compared with the intima (P < 0.0001) as well as in vascular smooth muscle cells (VSMCs) compared with the infiltrating macrophages (P < 0.0001). However, no significant difference in SC expression was observed between patients with and without T2D. No correlation was found between serum and immunohistochemical levels of SC; significantly increased SC serum levels were detected in males compared with females (P = 0.049). CONCLUSIONS: We have demonstrated, for the first time, the expression of SC in VSMCs of atherosclerotic plaques, suggesting a potential role for this protein in the development of atherosclerosis. Further studies are needed to understand if the role played by SC is detrimental or protective in the atherosclerotic disease process.