Impact of in vitro SARS-CoV-2 infection on breast cancer cells.

The pandemic of coronavirus disease 19 (COVID-19), caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), had severe repercussions for breast cancer patients. Increasing evidence indicates that SARS-CoV-2 infection may directly impact breast cancer biology, but the effects of SARS-CoV-2 on breast tumor cells are still unknown. Here, we analyzed the molecular events occurring in the MCF7, MDA-MB-231 and HCC1937 breast cancer cell lines, representative of the luminal A, basal B/claudin-low and basal A subtypes, respectively, upon SARS-CoV-2 infection. Viral replication was monitored over time, and gene expression profiling was conducted. We found that MCF7 cells were the most permissive to viral replication. Treatment of MCF7 cells with Tamoxifen reduced the SARS-CoV-2 replication rate, suggesting an involvement of the estrogen receptor in sustaining virus replication in malignant cells. Interestingly, a metagene signature based on genes upregulated by SARS-CoV-2 infection in all three cell lines distinguished a subgroup of premenopausal luminal A breast cancer patients with a poor prognosis. As SARS-CoV-2 still spreads among the population, it is essential to understand the impact of SARS-CoV-2 infection on breast cancer, particularly in premenopausal patients diagnosed with the luminal A subtype, and to assess the long-term impact of COVID-19 on breast cancer outcomes.

Circulating perturbation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is associated to cardiac remodeling and NLRP3 inflammasome in cardiovascular patients with insulin resistance risk.

Lipidome perturbation occurring during meta-inflammation is associated to left ventricle (LV) remodeling though the activation of the NLRP3 inflammasome, a key regulator of chronic inflammation in obesity-related disorders. Little is known about phosphatidylcholine (PC) and phosphatidylethanolamine (PE) as DAMP-induced NLRP3 inflammasome. Our study is aimed to evaluate if a systemic reduction of PC/PE molar ratio can affect NLRP3 plasma levels in cardiovascular disease (CVD) patients with insulin resistance (IR) risk. Forty patients from IRCCS Policlinico San Donato were enrolled, and their blood samples were drawn before heart surgery. LV geometry measurements were evaluated by echocardiography and clinical data associated to IR risk were collected. PC and PE were quantified by ESI-MS/MS. Circulating NLRP3 was quantified by an ELISA assay. Our results have shown that CVD patients with IR risk presented systemic lipid impairment of PC and PE species and their ratio in plasma was inversely associated to NLRP3 levels. Interestingly, CVD patients with IR risk presented LV changes directly associated to increased levels of NLRP3 and a decrease in PC/PE ratio in plasma, highlighting the systemic effect of meta-inflammation in cardiac response. In summary, PC and PE can be considered bioactive mediators associated to both the NLRP3 and LV changes in CVD patients with IR risk.

Allografts use in orthopedic surgery: trend change over the past 11 years from a regional tissue bank.

Allografts are the second most transplanted tissue in medicine after blood and are now increasingly used for both primary and revision surgery. Allografts have the advantages of lower donor site morbidity, availability of multiple grafts, and shorter operative time. The Banks represents the bridge between Donor and Recipient and guarantees the quality and safety of the distributed allografts Given the increasing interest in these tissues, a retrospective analysis of data collected from the Regional Musculoskeletal Tissue Bank registry over an 11-year period (2009-2019) was conducted. The statistical analyses used were the Shapiro-Wilk normality test and a Poisson regression model. From January 2009 to December 2019, a total of 14,199 musculoskeletal tissues stored in the Regional Musculoskeletal Tissue Bank were provided for surgical allograft procedures. In 2009, the number of allografts performed was 925; this figure has steadily increased to 1599 in 2019. Epiphyses were taken as the reference tissue with an almost constant trend over the period, while a significant increase was denoted for extensor mechanism allograft, ligaments, tendons and long bone corticals (p < 0.001), processed bone tissues had no change in trend (p = 0.841). There was also a gradual decrease in the rate of microbiological positivity, as determined by bacteriological and serological tests performed on the collected tissues. This phenomenon is due to improved sampling techniques and the training of a dedicated team. Thus, we have seen how the use of allografts in orthopedic surgery has increased over the past 11 years, uniformly in terms of tissue type, except for the noticeable increase in ligamentous tissue.

Longitudinal study of human polyomaviruses viruria in kidney transplant recipients.

INTRODUCTION: Immunosuppression after kidney transplantation (KTx) exposes recipients to Human Polyomaviruses (HPyVs) infections, whose natural history is still misunderstood. METHODS: Allograft biopsies, and urine from 58 donor-recipient pairs were collected before KTx (T0) and 1 (T1), 15 (T2), 30 (T3), 60 (T4), 90 (T5), 180 (T6), 270 (T7), 360 (T8), and 540 (T9) days after transplant. Specimens were tested for JC (JCPyV) and BK (BKPyV), by quantitative Real-Time PCR. The course of post-KTx HPyVs viruria, and the association between JCPyV viruria in recipients and donors, were evaluated. RESULTS: HPyVs were detected in 3/58 (5.2%) allograft biopsies. HPyVs viruria was present in 29/58 (50%) donors and 41/58 (70.7%) recipients. JCPyV DNA was detected in 26/58 (44.8%) donors and 25/58 recipients (43.1%), 19 of whom received kidney from JCPyV positive donor, whereas BKPyV genome was detected in 3 (5.2%) donors and 22 (37.9%) recipients. The median time of JCPyV, and BKPyV first episode of replication was 1, and 171 days post KTx, respectively. At T0, JCPyV viruria of donors was associated with increased risk of JCPyV replication post-KTx; recipients with JCPyV positive donors showed lower risk of BKPyV replication post-KTx. CONCLUSIONS: The results suggested that JCPyV may be transmitted by allograft, and that its replication post KTx might prevent BKPyV reactivation. Future investigation regarding correlation between chronic exposure to immunosuppressive agents and HPyVs urinary replication are warranted.

Human cytomegalovirus-related gastrointestinal disease after kidney transplantation: A systematic review.

BACKGROUND: Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID). METHODS: We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs. RESULTS: Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3). CONCLUSIONS: The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.

Association of Oxygen Therapy with the Natural Disease Progression of Cystic Fibrosis: A Multi-State Model of the European Cystic Fibrosis Society Patient Registry.

Background: Association between dependence on oxygen therapy (OT) and natural disease progression in people with cystic fibrosis (pwCF) has not been estimated yet. The aim of this study is to understand the prognosis for pwCF on OT, evaluating how the transition probabilities from being alive without lung transplantation (LTx) to LTx and to death, and from being alive after LTx to death change in pwCF with and without OT. Methods: We used 2008-2017 data from the 35-country European CF Society Patient Registry. A multi-state model was fitted to assess the effects of individual risk factors on transition probabilities. Results: We considered 48,343 pwCF aged from 6 to 50 years. OT (HR 5.78, 95% CI: 5.32-6.29) and abnormal FEV1 (HR 6.41, 95% CI: 5.28-7.79) were strongly associated with the probability of having LTx; chronic infection with Burkholderia cepacia complex (HR 3.19, 95% CI: 2.78-3.67), abnormal FEV1 (HR 5.00, 95% CI: 4.11-6.08) and the need for OT (HR 4.32, 95% CI: 3.93-4.76) showed the greatest association with the probability of dying without LTx. Once pwCF received LTx, OT (HR 1.75, 95% CI: 1.41-2.16) and abnormal FEV1 (HR 1.63, 95% CI: 1.18-2.25) were the main factors associated with the probability of dying. An association of gross national income with the probability of receiving LTx and with the probability of dying without LTx was also found. Conclusion: Oxygen therapy is associated with poor survival in pwCF with and without LTx; harmonization of CF care throughout European countries and minimization of the onset of pulmonary gas exchange abnormalities using all available means remains of paramount importance.

Factors associated with perioperative mortality after late open conversion for failed endovascular aortic repair.

INTRODUCTION: The aim of this study was to perform a systematic review about the clinical and technical aspects of late open conversion for failed endovascular aortic repair (EVAR) of abdominal aortic aneurysms (AAA), and to investigate if the need for suprarenal aortic cross clamping, graft infection, urgent procedures, endoleaks and aortic rupture were associated with an increase of 30-days (perioperative) mortality. EVIDENCE ACQUISITION: A literature search was conducted on PubMed using the words "open conversion endovascular" on December 29th, 2021. Studies included randomized controlled trials, cohort studies, and case series of patients submitted to open conversion that were performed at least 1 month after the initial EVAR for AAA, reporting about 30-days mortality after surgery. A meta-analysis was performed to explore the association of suprarenal aortic cross clamping, graft infection, urgent procedures, endoleaks and aortic rupture with 30-days postoperative mortality using log odds ratios (ORs), with STATA/MP 17.0 (Stata Corp. 2021, LLC). Two-sided P values less than 0.05 were considered statistically significant. EVIDENCE SYNTHESIS: The search retrieved 985 results on PubMed from 1994 to 2021. Among them, 40 papers were included in the study for the systematic review, and 5 of them for the meta-analysis. A total of 2297 patients from 1992 to 2020 were submitted to open conversion after a median of 40.4 months from the initial EVAR. Endoleak was the most frequent cause of open conversion (76.3%). Perioperative mortality was 23.5% for urgent and 5.3% for elective conversions. At meta-analysis, urgent procedures and aortic rupture were both associated with higher perioperative mortality (OR 5.27, 95% CI 2.90-9.57 and OR 5.61, 95% CI 3.09-10.19 respectively). Similarly, patients with infections and who needed suprarenal aortic clamping were at higher risk of 30-days postoperative death (OR 3.74, 95% CI 1.96-7.13) and OR 2.23, 95% CI 1.24-4.02), while the presence of a preoperative endoleaks was not associated with a higher 30-days mortality. CONCLUSIONS: Late open conversion after EVAR of AAA is burdened by a perioperative mortality rate of 23.5% for urgent and 5.3% for elective cases. Urgent treatment, presence of aortic rupture or infection, and the need for suprarenal aortic cross clamping were associated with increased perioperative mortality, while the presence of an endoleak did not affect perioperative mortality.

Limitations of the dichotomized 6-minute walk distance when computing lung allocation score for cystic fibrosis: a 16-year retrospective cohort study.

PURPOSE: The 2010 Lung Allocation Score (LAS) version considers the estimated survival benefit offered by lung transplantation (LTx) and uses 6-minute Walk Test (6MWT) distance as a dichotomous covariate of whether an individual can walk more than 150 ft or 45.7 m in 6 min. This study aimed to provide evidence that 6MWT gives no clinically meaningful information to be used in the current LAS for candidates to LTx with cystic fibrosis (CF). MATERIALS AND METHODS: We collected data from 6MWTs performed since 2003 at our CF centre. A joint model was fitted to describe the effect of changes in walked distance on the hazard of LTx or death. RESULTS: Up to 2019, 552 6MWTs were performed on 163 individuals with CF. None of the individuals included walked for less than 45.7 m during the 6MWT. Based on the joint modelling, the association of walked distance with the hazard ratio (HR) of LTx or death was significant (HR 0.99, 95% Credible Interval [CI]: 0.99 to 1.00). CONCLUSIONS: When adopted dichotomously for LAS calculation, walked distance does not add any useful information about exercise capacity. Longitudinal trajectories of walked distance may provide complementary information about prognosis in individuals with CF.Implications for rehabilitationDichotomized walked distance does not contribute to lung allocation score in candidates to lung transplantation with cystic fibrosisChanges in the longitudinal trajectory of walked distance can be clinically meaningful for prognostication.Sensitive outcomes to be incorporated in the lung allocation scoring system for individuals with CF are yet needed to catch rapid falls in functional capacity.

Live or Heat-Killed Lactobacillus rhamnosus Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model.

An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin (V/N)-aerosolized or live or dead L. rhamnosus GG (L.RGG)-aerosolized, and tumor development was evaluated. Transcriptional profiling of lungs and IHC were performed. Tumor nodules number, diameter and area were reduced by live or heat-killed L.RGG, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both L.RGG and V/N reduced Tregs in the lung. In L.RGG-treated groups, the gene encoding the joining chain (J chain) of immunoglobulins was increased, and higher J chain protein and IgA levels were observed. An increased infiltration of B, NK and myeloid-derived cells was predicted by TIMER 2.0. The Kaplan-Meier plotter revealed an association between high levels of J chain mRNA and good prognosis in lung adenocarcinoma patients that correlated with increased B and CD4 T cells and reduced Tregs and M2 macrophages. This study highlights L.RGG aerosol efficacy in impairing lung cancer growth by promoting local immunity and points to this non-invasive strategy to treat individuals at risk of lung cancer.

Differential Expression of the Genes Coding for Adipokines and Epithelial Cell Polarity Components in Women With Low and High Mammographic Density.

BACKGROUND: Women with extensive mammographic density (MD) are more likely to develop breast cancer than women with low MD because of a high epithelial component associated with a high proportion of stromal cells. To elucidate the biological association between high MD and risk of breast cancer, we compared the expression of a panel of genes coding for leptin, adiponectin, and some component of cell polarity and adherens junction complexes in dense and non-dense breast tissue. METHODS: We interrogated a public dataset composed by 120 specimens of normal breast tissue with MD evaluation. The differential expression of the selected genes in the 2 MD subgroups was assessed by the Wilcoxon test, whereas Kruskal-Wallis test evaluated the differential expression of single genes in the fatty, epithelium, or nonfatty compartment. Spearman's correlation measured the relationship among genes in the subset with the highest epithelium proportion. RESULTS: In high MD, the expression level of PARD6B, CRB3, PATJ, LLGL2, CDH1, and MARVELD2 significantly lowered in tissues with the highest epithelium proportion, whereas, in low MD, the expression level of the genes increased with the increasing of the epithelium proportion. In the low MD subgroup, LEP correlated negatively with PRKCZ and DLG3, whereas, in high MD, such correlation was not observed. CONCLUSIONS: The expression of the genes governing cell polarity establishment and cell-cell adhesion assembly differed significantly in the epithelial component of dense and non-dense breasts. The correlation pattern between LEP and PRKCZ or DLG3 agrees with the role of leptin in cell polarity disruption.

Lack of ApoA-I in ApoEKO Mice Causes Skin Xanthomas, Worsening of Inflammation, and Increased Coronary Atherosclerosis in the Absence of Hyperlipidemia.

BACKGROUND: HDL (high-density lipoprotein) and its major protein component, apoA-I (apolipoprotein A-I), play a unique role in cholesterol homeostasis and immunity. ApoA-I deficiency in hyperlipidemic, atheroprone mice was shown to drive cholesterol accumulation and inflammatory cell activation/proliferation. The present study was aimed at investigating the impact of apoA-I deficiency on lipid deposition and local/systemic inflammation in normolipidemic conditions. METHODS: ApoE deficient mice, apoE/apoA-I double deficient (DKO) mice, DKO mice overexpressing human apoA-I, and C57Bl/6J control mice were fed normal laboratory diet until 30 weeks of age. Plasma lipids were quantified, atherosclerosis development at the aortic sinus and coronary arteries was measured, skin ultrastructure was evaluated by electron microscopy. Blood and lymphoid organs were characterized through histological, immunocytofluorimetric, and whole transcriptome analyses. RESULTS: DKO were characterized by almost complete HDL deficiency and by plasma total cholesterol levels comparable to control mice. Only DKO showed xanthoma formation and severe inflammation in the skin-draining lymph nodes, whose transcriptome analysis revealed a dramatic impairment in energy metabolism and fatty acid oxidation pathways. An increased presence of CD4+ T effector memory cells was detected in blood, spleen, and skin-draining lymph nodes of DKO. A worsening of atherosclerosis at the aortic sinus and coronary arteries was also observed in DKO versus apoE deficient. Human apoA-I overexpression in the DKO background was able to rescue the skin phenotype and halt atherosclerosis development. CONCLUSIONS: HDL deficiency, in the absence of hyperlipidemia, is associated with severe alterations of skin morphology, aortic and coronary atherosclerosis, local and systemic inflammation.

Lung clearance index to characterize clinical phenotypes of children and adolescents with cystic fibrosis.

BACKGROUND: Lung clearance index (LCI) is accepted as an early marker of lung disease in cystic fibrosis (CF), however the utility of LCI to identify subgroups of CF disease in the paediatric age group has never been explored. The aim of the study was to characterize phenotypes of children with CF using LCI as a marker of ventilation inhomogeneity and to investigate whether these phenotypes distinguished patients based on time to pulmonary exacerbation (PE). METHODS: Data were collected on patients with CF aged < 18 years old, attending the CF Center of Milan during outpatient follow-up visits between October 2014 and September 2019. Cluster analysis using agglomerative nesting hierarchical method was performed to generate distinct phenotypes. Time-to-recurrent event analysis investigated association of phenotypes with PE. RESULTS: We collected 313 multiple breath washout tests on 125 children aged 5.5-16.8 years. Cluster analysis identified two divergent phenotypes in children and adolescents of same age, presenting with almost normal FEV1 but with substantial difference in markers of ventilation inhomogeneity (mean LCI difference of 3.4, 95% Confidence Interval [CI] 2.6-4.2). A less severe phenotype was associated with a lower risk of PE relapse (Hazard Ratio 0.45, 95% CI 0.34-0.62). CONCLUSIONS: LCI is useful in clinical practice to characterize distinct phenotypes of children and adolescents with mild/normal FEV1. A less severe phenotype translates into a lower risk of PE relapse.

Surgical Ventricular Restoration for Ischemic Heart Failure: A Glance at a Real-World Population.

Surgical ventricular restoration (SVR) has repeatedly been suggested as a viable therapeutic strategy for ischemic heart failure (HF) patients, although the survival benefit is still debated. We investigated a real-world population treated with SVR in a single center with high case volumes. From July 2001 to June 2017, 648 patients (111 females) underwent SVR; coronary surgery was performed in 582 patients. Data were analyzed by dividing the population into two groups: Group I (371 patients operated between July 2001 and December 2007) and Group II (277 patients operated between January 2008 and June 2017). At baseline, Group I patients were more symptomatic for angina (47.4% versus 19.4%, p < 0.0001) and less symptomatic for HF (NYHA class III/IV, 46.3% versus 57%, p = 0.0071). The end-diastolic volume (106 mL/m2 versus 118.3 mL/m2, p < 0.0001) and the end-systolic volume (70.5 mL/m2 versus 81.5 mL/m2, p < 0.0001) were lower in Group I. The presence of 3-vessel coronary artery disease (CAD) was higher in Group I (73.3% versus 59.2%, p < 0.0001). Thirty-day mortality (6.64%) was similar in the two groups (p = 0.4475). The Kaplan−Meier estimate for all-cause mortality for the entire population was 13% at 2 years, 19.2% at 4 years and 36.6% at 8 years, and the probability was not different between groups (Log-rank = 0.11). In a real-world ischemic HF population, SVR may be carried out with favorable results; in patients with worse LV remodeling and less extensive CAD, SVR showed a trend toward a better outcome.

Arthroscopic Rotator Cuff Repair Augmentation With Autologous Microfragmented Lipoaspirate Tissue Is Safe and Effectively Improves Short-term Clinical and Functional Results: A Prospective Randomized Controlled Trial With 24-Month Follow-up.

BACKGROUND: Autologous microfragmented lipoaspirate tissue has been recently introduced in orthopaedics as an easily available source of nonexpanded adipose-derived mesenchymal stem cells. Autologous microfragmented lipoaspirate tissue is expected to create a suitable microenvironment for tendon repair and regeneration. Rotator cuff tears show a high incidence of rerupture and represent an ideal target for nonexpanded mesenchymal stem cells. PURPOSE: To evaluate the safety and efficacy of autologous lipoaspirate tissue in arthroscopic rotator cuff repair. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: Consecutive patients referring to the investigation center for surgical treatment of magnetic resonance imaging-confirmed degenerative posterosuperior rotator cuff tears were assessed for eligibility. Those who were included were randomized to receive a single-row arthroscopic rotator cuff repair, followed by intraoperative injection of autologous microfragmented adipose tissue processed with an enzyme-free technology (treatment group) or not (control group). Clinical follow-up was conducted at 3, 6, 12, 18, and 24 months; at 18 months after surgery, magnetic resonance imaging of the operated shoulder was obtained to assess tendon integrity and rerupture rate. RESULTS: An overall 177 patients were screened, and 44 (22 per group) completed the 24-month follow-up. A statistically significant difference in favor of the treatment group in terms of Constant-Murley score emerged at the primary endpoint at 6-month follow-up (mean ± SD; control group, 76.66 ± 10.77 points; treatment group, 82.78 ± 7.00 points; P = .0050). No significant differences in clinical outcome measures were encountered at any of the other follow-up points. No significant differences emerged between the groups in terms of rerupture rate, complication rate, and number of adverse events. CONCLUSION: This prospective randomized controlled trial demonstrated that the intraoperative injection of autologous microfragmented adipose tissue is safe and effective in improving short-term clinical and functional results after single-row arthroscopic rotator cuff repair. REGISTRATION: NCT02783352 (ClinicalTrials.gov identifier).

Organ Donation after Damage Control Strategy in Trauma Patients: Experience from First Level Trauma Center in Italy.

BACKGROUND: Organ donation (OD) remains the only therapeutic option for end-stage disease in some cases. Unfortunately, the gap between donors and recipients is still substantial. Trauma patients represent a potential yet underestimated pool of organ donors. In this article, we present our data on OD after damage control strategy (DCS). MATERIALS AND METHODS: A retrospective, observational cohort study was conducted through a complete revision of data of consecutive adult trauma patients (>18 years old) who underwent OD after DCS between January 2018 and May 2021. Four subgroups were created [Liver (Li), Lungs (Lu), Heart (H), Kidneys (K)] to compare variables between those who donated the organ of interest and those who did not. RESULTS: Thirty-six patients underwent OD after DCS. Six patients (16.7%) were excluded: 2(5.6%) for missing data about admission; 4(11.1%) didn't receive DCS. Mean ISS was 47.2 (SD ± 17.4). Number of donated organs was 113 with an organs/patient ratio of 3.8. The functional response rate was 91.2%. Ten organs (8.8%) had primary nonfunction after transplantation: 2/15 hearts (13.3%), 1/28 livers (3.6%), 4/53 kidneys (7.5%) and 3/5 pancreases (60%). No lung primary nonfunction were registered. Complete results of subgroup analysis are reported in supplementary materials. CONCLUSION: Organ donation should be considered a possible outcome in any trauma patient. Aggressive damage control strategy doesn't affect the functional response rate of transplanted organs.

Magnesium alginate versus proton pump inhibitors for the treatment of laryngopharyngeal reflux: a non-inferiority randomized controlled trial.

PURPOSE: Proton pump inhibitors (PPIs) are commonly prescribed for laryngopharyngeal reflux (LPR), but their efficacy remains debated. Alginates is an option for the treatment of LPR with few adverse effects. The study aimed to investigate the non-inferiority of an alginate suspension (Gastrotuss®) compared to PPIs (Omeprazole) in reducing LPR symptoms and signs. METHODS: A non-inferiority randomized controlled trial was conducted. Fifty patients with laryngopharyngeal symptoms (Reflux Symptom Index -RSI- ≥ 13) and signs (Reflux Finding Score -RFS- ≥ 7) were randomized in two treatment groups: (A) Gastrotuss® (20 ml, three daily doses) and, (B) Omeprazole (20 mg, once daily). The RSI and the RFS were assessed at baseline and after 2 months of treatment. RESULTS: Groups had similar RSI and RFS scores at baseline. From pre- to 2-month posttreatment, the mean RSI significantly decreased (p = 0.001) in alginate and PPI group (p = 0.003). The difference between groups in the RSI change was not significant (95%CI:  - 4.2-6.7, p = 0.639). The mean RFS significantly decreased in alginate (p = 0.006) and PPI groups (p = 0.006). The difference between groups in the mean change RFS was not significant (95%CI:  - 0.8; 1.4, p = 0.608). CONCLUSION: After 2 months of treatment, LPR symptoms and signs are significantly reduced irrespective of the treatment. Alginate was non-inferior to PPIs and may represent an alternative treatment to PPIs for the treatment of LPR.

Prevalence and factors associated with urinary incontinence in females with cystic fibrosis: An Italian single-center cross-sectional analysis.

BACKGROUND: Individuals with cystic fibrosis (CF) are deemed to have a higher risk of developing urinary incontinence (UI), likely due to repeated increasing pressure on the pelvic floor. We aimed to determine the prevalence of female UI in a large CF referral center, and to assess the association between UI and severity of CF disease. METHODS: We consecutively recruited female patients regularly attending our CF center, aged ≥6 years and with a confirmed diagnosis of CF. Prevalence, severity, and impact of UI were assessed by administering two validated questionnaires. Relationship between variables was evaluated by means of multiple correspondence analysis, whereas a logistic model was fitted to capture the statistical association between UI and independent variables. RESULTS: UI was present in 51/153 (33%, 95% confidence interval [CI]: 26%-41%) females. Among children and adolescents, the prevalence was 12/82 (15%, 95% CI: 8%-25%) whereas among adults was 39/71 (55%, 95% CI: 43%-67%). The only explanatory variable associated with UI was age, with children presenting the lowest risk (odds ratio, 0.32; 95% CI: 0.05-0.93). Females presenting low or high nutritional status show higher profile risk of having UI. CONCLUSIONS: Stress UI is a common complication in females with CF since childhood. Although it frequently occurs in older patients with a more severe phenotype, much attention should be paid to adults and to their nutritional status.

Challenging Giant Insular Gliomas With Brain Mapping: Evaluation of Neurosurgical, Neurological, Neuropsychological, and Quality of Life Results in a Large Mono-Institutional Series.

OBJECTIVE: Giant insular tumors are commonly not amenable to complete resection and are associated with a high postoperative morbidity rate. Transcortical approach and brain mapping techniques allow to identify peri-insular functional networks and, with neurophysiological monitoring, to reduce vascular-associated insults. Cognitive functions to be mapped are still under debate, and the analysis of the functional risk of surgery is currently limited to neurological examination. This work aimed to investigate the neurosurgical outcome (extent of resection, EOR) and functional impact of giant insular gliomas resection, focusing on neuropsychological and Quality of Life (QoL) outcomes. METHODS: In our retrospective analysis, we included all patients admitted in a five-year period with a radiological diagnosis of giant insular glioma. A transcortical approach was adopted in all cases. Resections were pursued up to functional boundaries defined intraoperatively by brain mapping techniques. We examined clinical, radiological, and intra-operative factors possibly affecting EOR and postoperative neurological, neuropsychological, and Quality of Life (QoL) outcomes. RESULTS: We finally enrolled 95 patients in the analysis. Mean EOR was 92.3%. A Gross Total Resection (GTR) was obtained in 70 cases (73.7%). Five patients reported permanent morbidity (aphasia in 3, 3.2%, and superior quadrantanopia in 2, 2.1%). Suboptimal EOR associated with poor seizures control postoperatively. Extensive intraoperative mapping (inclusive of cognitive, visual, and haptic functions) decreased long-term neurological, neuropsychological, and QoL morbidity and increased EOR. Tumor infiltration of deep perforators (vessels arising either medial to lenticulostriate arteries through the anterior perforated substance or from the anterior choroidal artery) associated with a higher chance of postoperative ischemia in consonant areas, with the persistence of new-onset motor deficits 1-month post-op, and with minor EOR. Ischemic insults in eloquent sites represented the leading factor for long-term neurological and neuropsychological morbidity. CONCLUSION: In giant insular gliomas, the use of a transcortical approach with extensive brain mapping under awake anesthesia ensures broad insular exposure and extension of the surgical resection preserving patients' functional integrity. The relation between tumor mass and deep perforators predicts perioperative ischemic insults, the most relevant risk factor for long-term and permanent postoperative morbidity.

Association of supratotal resection with progression-free survival, malignant transformation, and overall survival in lower-grade gliomas.

BACKGROUND: Supratotal resection is advocated in lower-grade gliomas (LGGs) based on theoretical advantages but with limited verification of functional risk and data on oncological outcomes. We assessed the association of supratotal resection in molecularly defined LGGs with oncological outcomes. METHODS: Included were 460 presumptive LGGs; 404 resected; 347 were LGGs, 319 isocitrate dehydrogenase (IDH)-mutated, 28 wildtype. All patients had clinical, imaging, and molecular data. Resection aimed at supratotal resection without any patient or tumor a priori selection. The association of extent of resection (EOR), categorized on volumetric fluid attenuated inversion recovery images as residual tumor volume, along with postsurgical management with progression-free survival (PFS), malignant (M)PFS, and overall survival (OS) assessed by univariate, multivariate, and propensity score analysis. The study mainly focused on IDH-mutated LGGs, the "typical LGGs." RESULTS: Median follow-up was 6.8 years (interquartile range, 5-8). Out of 319 IDH-mutated LGGs, 190 (59.6%) progressed, median PFS: 4.7 years (95% CI: 4-5.3). Total and supratotal resection obtained in 39% and 35% of patients with IDH1-mutated tumors. In IDH-mutated tumors, most patients in the partial/subtotal group progressed, 82.4% in total, only 6 (5.4%) in supratotal. Median PFS was 29 months (95% CI: 25-36) in subtotal, 46 months (95% CI: 38-48) in total, while at 92 months, PFS in supratotal was 94.0%. There was no association with molecular subtypes and grade. At random forest analysis, PFS strongly associated with EOR, radiotherapy, and previous treatment. In the propensity score analysis, EOR associated with PFS (hazard ratio, 0.03; 95% CI: 0.01-0.13). MPFS occurred in 32.1% of subtotal total groups; 1 event in supratotal. EOR, grade III, previous treatment correlated to MPFS. At random forest analysis, OS associated with EOR as well. CONCLUSIONS: Supratotal resection strongly associated with PFS, MPFS, and OS in LGGs, regardless of molecular subtypes and grade, right from the beginning of clinical presentation.

Comparable outcomes between genders in patients undergoing surgical ventricular reconstruction for ischaemic heart failure.

AIMS: Female sex and heart failure (HF) are considered poor prognostic factors for surgery. We aimed to investigate the association between sex and surgical outcomes in patients with ischaemic HF undergoing surgical ventricular reconstruction and coronary artery bypass grafting. METHODS AND RESULTS: From July 2001 to June 2017, 648 patients [111 women (17%) and 537 men (83%)] were referred to our centre. Follow-up continued through June 2018. All patients underwent surgical ventricular reconstruction; coronary artery bypass grafting was performed in 582 patients (90%). Primary outcome was defined as all-cause mortality. Secondary outcome included all-cause mortality or all-cause hospitalization. Women were older (70 vs. 65 years, P < 0.0001) with lower body surface area (1.70 vs. 1.86 m2 , P < 0.0001). Women had more diabetes (36% vs. 24%, P = 0.005) and a higher New York Heart Association classification (Class III/IV 65.7% vs. 47.8%, P = 0.0006), without any significant difference in medical therapy except for a higher use of oral antidiabetic agents in women (P = 0.029). At baseline, the left ventricular (LV) end-diastolic volume index was significantly lower in women [median 107.06 (80.6-127.81) vs. 113. 04 (94.33-135.52) mL/m2 , P = 0.0078] but not the LV end-systolic volume index (ESVI) [median 73.45 (51.93-96.79) vs. 77.03 (60.33-95.71) mL/m2 , P = 0.1393] and the ejection fraction (median 31% vs. 32%, P = 0.150). Women had a higher rate of anterior remodelling (90.9% vs. 79.1%, P = 0.0129), without evidence of differences in mitral valve insufficiency (P = 0.761 for Grade 0 to 4) and mitral surgery (P = 0.810). After surgery, the percentage of reduction in LV ESVI was higher in women than in men (median ΔLV ESVI -42.06 vs. -31.99, P = 0.0003). Mortality within 30 days occurred in 43 patients (6.64%): 12 women (10.81%) and 31 men (5.77%, P = 0.0522). Over a median follow-up of 9.8 years, all-cause mortality occurred in 269 patients (41.64%), without significant difference between women (45.9%) and men (40.7%). There was no evidence of difference of all-cause death between sexes (log-rank = 0.2441). When considering mortality and first hospitalization as competing events, Gray's test showed no difference of cumulative incidence functions (all-cause hospitalization, all-cause death, and combined endpoint) according to sex (P = 0.909, P = 0.445, and P = 0.429, respectively). CONCLUSIONS: In this study, long-term outcomes for women and men with ischaemic HF undergoing complex cardiac surgery were equivalent. Albeit older and more symptomatic, women should not be denied this type of cardiac surgery.