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Gastroenterology, Digestive Endoscopy and Hepatology have faced significant improvements in terms of diagnosis and therapy in the last decades. However, many fields still remain poorly explored, and many questions unanswered. Moreover, basic-science, as well as translational and clinical discoveries, together with technology advancement will determine further steps toward a better, refined care for many gastroenterological disorders in the future. Therefore, the Young Investigators of the Italian Society of Gastroenterology (SIGE) joined together, offering a perspective on major future innovations in some hot clinical topics in Gastroenterology, Endoscopy, and Hepatology, as well as the current pitfalls and the grey zones.

Background Chemotherapy-induced neutropenia (CIN) has been demonstrated to be a prognostic factor in several cancer conditions. We previously found a significant prognostic value of CIN on overall survival (OS), in a pooled dataset of patients with advanced non-small-cell lung cancer (NSCLC) receiving first line chemotherapy from 1996 to 2001. However, the prognostic role of CIN in NSCLC is still debated. Methods We performed a post hoc analysis pooling data prospectively collected in six randomized phase 3 trials in NSCLC conducted from 2002 to 2016. Patients who never started chemotherapy and those for whom toxicity data were missing were excluded. Neutropenia was categorized on the basis of worst grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). The primary endpoint was OS. Multivariable Cox model was applied for statistical analyses. In the primary analysis, a minimum time (landmark) at 180 days from randomization was applied in order to minimize the time-dependent bias. Results Overall, 1529 patients, who received chemotherapy, were eligible; 572 of them (who received 6 cycles of treatment) represented the landmark population. Severe CIN was reported in 143 (25.0%) patients and mild CIN in 135 (23.6%). At multivariable OS analysis, CIN was significantly predictive of prognosis although its prognostic value was entirely driven by severe CIN (hazard ratio [HR] of death 0.71; 95%CI: 0.53–0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92–1.58). Consistent results were observed in the out-of-landmark group (including 957 patients), where both severe and mild CIN were significantly associated with a reduced risk of death. Conclusion The pooled analysis of six large trials of NSCLC treatment shows that CIN occurrence is significantly associated with a longer overall survival, particularly in patients developing severe CIN, confirming our previous findings.

Introduction This retrospective consecutive study compared standalone implantation of multiple (2–3) trabecular micro-bypass stents (iStent inject ± iStent) (Multi-Stent group) vs trabeculectomy + mitomycin C (Trab group) in moderate to severe open-angle glaucoma (OAG). Methods Eligible patients underwent Multi-Stent or Trab surgery from 2018 to 2020 and had at least 3-month follow-up; visual field mean deviation (VF MD) − 6 dB or worse; inadequate prior response to maximum medications ± laser procedures; and had trabeculectomy as their next planned intervention. Primary effectiveness, safety-adjusted treatment success, was defined as ≥ 20% intraocular pressure (IOP) reduction on the same or fewer medications, without clinically significant safety events (severe complications, secondary surgeries, reinterventions). Secondary effectiveness included mean IOP and medications; qualified and complete attainment of target IOP (≤ 21/18/15/12 mmHg and > 6 mmHg); health-economic and quality-of-life (QoL) measures; and 2-vs-3-stent subgroup analysis. Results The baseline groups (n = 70 Multi-Stent/40 Trab) were similar: mean IOP (21.1 mmHg/22.3 mmHg); medications (2.87/3.10 medications); disease stage (30%/35% severe); VF MD (− 10.1 dB/− 10.4 dB); and mean last follow-up (LFU, 13.1 months/15.7 months) (all differences non-significant). Primary effectiveness: treatment success at LFU was 62.9% vs 30.0% in Multi-Stent vs Trab eyes, respectively (p = 0.001). Secondary effectiveness: At LFU in Multi-Stent vs Trab groups, respectively: mean IOP decreased by 31% to 14.2 mmHg (p

Background Patients who require readmission to an intensive care unit (ICU) after transfer to a lower level of care (“bounceback”) suffer from increased mortality and longer hospital stays. We aimed to create a multifaceted standardized transfer process for patients moving from the neurointensive care unit (neuro-ICU) to a lower level of care. We hypothesized that this process would lead to improvement in provider-rated safety and a decreased rate of bouncebacks to the neuro-ICU after transfer. Methods The study took place at the Hospital of the University of Pennsylvania from October 2018 to October 2020. A standardized five-step transfer process was created and implemented for transferring patients from the neuro-ICU to a lower level of care. Patient care providers completed a survey before and after implementation of the protocol to assess a variety of components related to safety concerns when transferring patients. The rate of bouncebacks pre and post intervention was calculated by using a two-sample Wilcoxon rank-sum test, and disposition at discharge was calculated by using Fisher’s exact test. Results Of the 1176 total patient transfers out of the neuro-ICU, 29 patients bounced back within 48 h. The average age of patients who bounced back was 63.3 years old, with a similar distribution among men and women. The most common reason for bounceback was respiratory distress, followed by cardiac arrhythmia, stroke, and sepsis. Implementation of the standardized process led to a decrease in provider-rated concern of overall safety (5 to 3, p = 0.008). There was improvement in transfer delays due to bed availability (3 to 4.5, p = 0.020), identification of high-risk patients (5 to 6, p = 0.021), patient assignment to the appropriate level of care (5 to 6, p = 0.019), and use of the electronic medical record handoff indicator (5 to 6, p = 0.003). There was no statistically significant difference in terms of patient bounceback rate after implementation of the process (2.4% vs. 2.5%, p = 1.00) or patient disposition at discharge (p = 0.553). Conclusions Patients who bounceback to the neuro-ICU within 48 h had an increased length of hospital stay, had an increased length of ICU stay, and were more likely to be intubated for more than 96 h. Implementation of a standardized five-step transfer process from the neuro-ICU to a lower level of care resulted in improvement in multiple provider-rated safety outcomes and identification of high-risk patients but led to no difference in the patient bounceback rate or patient disposition at discharge. Supplementary Information The online version contains supplementary material available at 10.1007/s12028-021-01385-z.

Background: In accordance with the scientific literature heavy alcohol consumption (>50g per day) represents a risk factor for several diseases development, including cancer. However, the oncogenic role of light alcohol drinking ( Objective: To assess the scientific knowledge about light alcohol consumption and the risk of malignancy onset. Methods: To collect the scientific evidences regarding this topic the keywords “light alcohol drinking”, “light alcohol consumption” and “cancer”, were used. Papers published during the last 15 years were analyzed, in order to select the most recent evidence. Meta-analyses with well-defined levels of alcohol intake were included in the present review. Other studies that focused on biochemical, molecular and genetic aspects, as well as duplicate articles, were excluded. : Furthermore, a possible protective role of light alcohol consumption on the development of bladder, kidney and ovarian cancer and Non Hodgkin Lymphoma was observed. Results: Twenty-nine large, meta-analyses were included in this review. Light alcohol drinking was not associated with an increased risk of cancer occurrence, with the exception of breast and prostate cancer and melanoma. Conclusion: Light alcohol drinking was not associated with the development of several malignancies, except for a light increase of melanoma, breast cancer in women and prostate cancer in men.

Total and subtotal sternectomy oncological defects can result in large deficits in the chest wall, disrupting the biomechanics of respiration. Reviewing the current literature involving respiratory function and rib motion after sternectomy, autologous rigid reconstruction was determined to provide the optimal reconstructive option. We describe a novel technique for sternal defect reconstruction utilizing a double-barrel, longitudinally oriented, vascularized free fibula flap associated with rib titanium plates fixation. Our reconstructive approach was able to deliver a physiological reconstruction, providing rigid support and protection while allowing articulation with adjacent ribs and preservation of chest wall mechanics.

No robust evidence is provided by literature regarding the management of intracranial hypertension following severe traumatic brain injury (TBI). This is mostly due to the lack of prospective randomized controlled trials (RCTs), the presence of studies containing extreme heterogeneously collected populations and controversial considerations about chosen outcome. A scientific society should provide guidelines for care management and scientific support for those areas for which evidence-based medicine has not been identified. However, RCTs in severe TBI have failed to establish intervention effectiveness, arising the need to make greater use of tools such as Consensus Conferences between experts, which have the advantage of providing recommendations based on experience, on the analysis of updated literature data and on the direct comparison of different logistic realities. The Italian scientific societies should provide guidelines following the national laws ruling the best medical practice. However, many limitations do not allow the collection of data supporting high levels of evidence for intracranial pressure (ICP) monitoring and decompressive craniectomy (DC) in patients with severe TBI. This intersociety document proposes best practice guidelines for this subsetting of patients to be adopted on a national Italian level, along with joint statements from "TBI Section" of the Italian Society of Neurosurgery (SINch) endorsed by the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). Presented here is a recap of recommendations on management of ICP and DC supported a high level of available evidence and rate of agreement expressed by the assemblies during the more recent consensus conferences, where members of both groups have had a role of active participants and supporters. The listed recommendations have been sent to a panel of experts consisting of the 107 members of the "TBI Section" of the SINch and the 111 members of the Neuroanesthesia and Neurocritical Care Study Group of the SIAARTI. The aim of the survey was to test a preliminary evaluation of the grade of predictable future adherence of the recommendations following this intersociety proposal. The following recommendations are suggested as representing best clinical practice, nevertheless, adoption of local multidisciplinary protocols regarding thresholds of ICP values, drug therapies, hemostasis management and perioperative care of decompressed patients is strongly recommended to improve treatment efficiency, to increase the quality of data collection and to provide more powerful evidence with future studies. Thus, for this future perspective a rapid overview of the role of the multimodal neuromonitoring in the optimal severe TBI management is also provided in this document. It is reasonable to assume that the recommendations reported in this paper will in future be updated by new observations arising from future trials. They are not binding, and this document should be offered as a guidance for clinical practice through an intersociety agreement, taking in consideration the low level of evidence.

The GIM2 phase III trial demonstrated the benefit of dose-dense chemotherapy in node-positive early breast cancer (eBC). To better define the dose-dense effect in the hormone receptor-positive subgroup, we evaluated its benefit through a composite measure of recurrence risk. We conducted an ancillary analysis of the GIM2 trial evaluating the absolute treatment effect through a composite measure of recurrence risk (CPRS) in patients with hormone receptor-positive HER2-negative eBC. CPRS was estimated through Cox proportional hazards models applied to the different clinicopathological features. The treatment effect was compared to the values of CPRS by using the Sub-population Treatment Effect Pattern Plot (STEPP) process. The Disease-Free Survival (DFS)-oriented STEPP analysis showed distinct patterns of relative treatment effect with respect to CPRS. Overall, 5-year DFS differed across CPRS quartiles ranging from 95.2 to 66.4%. Each CPRS quartile was characterized by a different patients’ composition, especially for age, lymph node involvement, tumor size, estrogen and progesterone receptor expression, and Ki-67. A number needed to treat of 154 and 6 was associated with the lowest and the highest CPRS quartile, respectively. Dose-dense adjuvant chemotherapy showed a consistent benefit in node-positive eBC patients with hormone receptor-positive HER2-negative disease, but its effect varied according to CPRS.

Ricardo Augusto Paletta Guedes,1 Daniela Marcelo Gravina,1 Vanessa Maria Paletta Guedes,1 Alfredo Chaoubah2 1Glaucoma Department, Paletta Guedes Eye Institute, Juiz de Fora, MG, Brazil; 2Statistics Department, Federal University of Juiz De Fora, Juiz de Fora, MG, BrazilCorrespondence: Ricardo Augusto Paletta GuedesGlaucoma Department, Paletta Guedes Eye Institute, 79, Oscar Vidal streeet, Juiz de Fora, MG, 36010-060, BrazilTel: +55 32 3213-1927Email palettaguedes@yahoo.comIntroduction: This retrospective comparative study assessed real-world effectiveness and safety of first-generation (iStent®) and second-generation (iStent inject®) trabecular micro-bypass stents with cataract surgery in patients with open-angle glaucoma (OAG).Material and Methods: Through a 24-month postoperative follow-up, the effectiveness was quantified by intraocular pressure (IOP) reduction; mean glaucoma medication reduction; proportional analysis of eyes meeting IOP cutoffs (< 18, < 15, < 12 mmHg) either with or without medications; and proportional analysis of medication burden. Safety measures included visual acuity, adverse events, and secondary surgery.Results: A total of 82 consecutive eyes (39 iStent, 43 iStent inject) with a 24-month follow-up were analyzed. Most eyes (74.4%) had primary open-angle glaucoma, with the remainder having pseudoexfoliative or pigmentary glaucoma; all eyes had mild-to-moderate disease. At 24 months postoperative, the mean IOP was lower, and the percent reduction from baseline was greater, in iStent inject eyes (26.0% reduction, 17.7mmHg to 13.1mmHg) than in iStent eyes (9.8% reduction, 16.4mmHg to 14.8mmHg) (between-groups comparison, p=0.019). Within each group, the postoperative IOP reduction was greater in eyes with higher baseline IOP (p< 0.001). Medication burden decreased significantly in both groups, from 1.74 to 0.51 mean medications for iStent (70.7% reduction, p< 0.0001), and 2.19 to 0.65 for iStent inject (70.3% reduction, p< 0.0001). Both groups exhibited excellent safety.Conclusion: iStent or iStent inject with phacoemulsification produced significant IOP and medication reductions, with effects enduring for two years. IOP reductions were greater for iStent inject than for iStent. Within each group, higher preoperative IOP was associated with greater postoperative IOP reduction.Keywords: iStent, iStent inject, trabecular micro-bypass, micro-invasive, MIGS

Fear of falling (FOF) has important clinical and psychological consequences. This study evaluated the factors associated with FOF in hemodialysis patients and compared with the FOF reported by age–gender matched individuals without chronic kidney disease. This cross sectional study included hemodialysis group (n = 60, 55.4 ± 7.6 years, 55.0% male) and control group (n = 40, 55.1 ± 7.5 years, 52.5% male). FOF was assessed by the Falls Efficacy Scale International (FES-I). Physical function was evaluated using the Mini-Balance Evaluation Systems Test (Mini-BESTest), Timed Up and Go test, 4-m gait speed, isometric handgrip force and 10-repetition sit-to-stand test. The physical and mental components of quality of life was evaluated by 36-Item Short Form Health Survey. The FES-I score was higher in the hemodialysis group compared to the control group (28.2 ± 9.7 vs. 23.3 ± 5.1, p = 0.020). In addition, the prevalence of individuals with a higher concern about falling was greater in the hemodialysis group (41.7 vs. 17.5%, p = 0.033). Multiple linear regression showed that the FES-I score was associated with the Mini-BESTest score and the physical component summary of quality of life (coefficient of determination of 0.51 and an adjusted coefficient of determination of 0.46). FOF was associated with poor postural balance and reduced physical component of quality of life in patients on hemodialysis and these patients showed higher FOF compared to individuals without chronic kidney disease.

The effectiveness of performance feedback depends on many factors, including accuracy and repeated delivery over time. Previous research has suggested that requiring the delivery of performance feedback may result in less accurate observations and feedback during subsequent observations. The current study evaluated whether different reactions (i.e., positive, neutral, or negative) to feedback would affect the accuracy of subsequent observations or the delivery of feedback. Forty-five participants were assigned to 1 of 3 reactions groups and they were instructed to observe and record the safety performance of a confederate during a baseline condition. Following 2 baseline sessions, participants were instructed to deliver feedback and the confederate reacted to the feedback according to the assigned condition for 4 sessions. Results provide evidence that positive reactions maintain observation accuracy and the provision of feedback, while both neutral and negative reactions decrease observation accuracy and result in frequent omission of feedback.

Efforts have been made to determine new predictors of morbidity and mortality in patients with severe burn injuries. This prospective cohort study aimed to determine the association of serum albumin concentration on admission and renal failure, pulmonary infection, sepsis, and death in patients with burn injuries. We included 141 patients, aged >18 years, who were admitted to our institution between April and August 2018. Among them, 59.1% were male and 83.8% had burns covering 2.2 g/dL (odds ratios [OR]: 18.7; 95% confidence interval [CI]: 4.9 to 70.8). Serum albumin ≤2.2 g/dL was also significantly associated with pulmonary infection (OR: 13.1, 95% CI: 3.8 to 45.7), renal failure (OR: 30.2, 95% CI: 7.4 to 122.3), and sepsis (OR: 16.9, 95% CI: 4.9 to 58.3). Serum albumin concentration cut-points and ABSIs were determined to be death predictors using areas under the receiver operating characteristic curves (AUCs). The AUCs with albumin or ABSI alone were 0.89 (95% CI: 0.79 to 0.98) and 0.92 (95% CI: 0.87 to 0.96), respectively. The AUC including both albumin and ABSI was 0.96 (95% CI: 0.90 to 0.98), indicating that the combination is a better death predictor than either measure alone. We confirmed that burn patients with a serum albumin concentration ≤2.2 g/dL on admission have substantially increased morbidity and mortality.

Rasopathies are a group of phenotypically overlapping conditions that include Noonan, Noonan with multiple lentigines, Noonan with loose anagen hair, Costello, Cardio-facio-cutaneous, and Neurofibromatosis-Noonan syndromes. Noonan syndrome with loose anagen hair (NS-LAH) is clinically characterized by prominent forehead, macrocephaly, growth hormone deficiency, sparse, loose and slow-growing anagen hair, hyperpigmented skin with eczema or ichthyosis, mild psychomotor delays, hypernasal voices, and attention deficit hyperactivity disorder. Variants in SHOC2 are responsible for the majority of the cases. Gripp et al. identified four unrelated individuals with similar phenotype to NS-LAH with pathogenic variants in PPP1CB. In this study, we present one family and one patient with NS-LAH and variants in PPP1CB. The first patient belongs to a family with a likely pathogenic variant, c.545T>A (p.Met182Lys), the first family published so far with a variant in this gene. The second patient harbors a de novo pathogenic variant, c.146C>G (p.Pro49Arg). This study presents two additional patients with this rare syndrome in order to increase the clinical characterization of the syndrome and provide more evidence of the pathogenicity of the c.545T>A (p.Met182Lys) variant in PPP1CB, a gene recently associated with NS-LAH.

Introduction: The immunosuppressive efficiency obtained in the last decades in kidney transplantation significantly improved graft survival. However, there is still a high risk and incidence of cancer in transplant patients strongly and directly related to the type of immunosuppression. An increasing body of evidence suggests that the PI3K/Akt/mTOR pathway may play a pivotal role in the development and progression of several neoplastic diseases. Case Presentation: We describe a 47-year-old male patient who received a cadaveric primary renal transplant in November 2008 developing a poorly differentiated infiltrating and ulcerated squamous cell carcinoma (SCC) at the eye level. In this patient, the modification of an immunosuppressive regimen with introduction of rapamycin (mTOR) inhibitors and withdrawal of calcineurin inhibitors (CNIs) led to the resolution of this severe condition. Conclusion: The introduction of mTOR inhibitors and withdrawal of CNIs in kidney-transplanted patients with de novo eye SCC should be considered in this clinical setting.

Background Complex elbow injuries (CEIs) are severe and rare lesions, difficult to treat correctly due to the different patterns of clinical presentations. Standard methods cannot often be applied. The main goals of the treatment are performing a stable osteosynthesis of all fractures, obtaining a concentric and stable reduction of the elbow by repairing the soft tissue constraint lesions, and allowing early motion. Since the introduction of virtual reality (VR) approaches in clinical practice, three-dimensional (3D) computed tomography (CT) and 3D printing have revolutionised orthopaedic surgeries, thus helping to understand the anatomy and the pathology of complex cases. Case description We discussed a case of CEI, characterised by an extended soft tissue (IIIB Gustilo classification) and neurovascular lesions associated with bone loss in a young female patient. Olecranon fracture was type IIIB according to Mayo classification. We outlined the steps of a pluri-tissue reconstructive approach and stressed the importance of 3D printing in the preoperative planning for such cases. Finally, peculiar final functional patient outcomes were reported. Conclusion In this case, we found out that triceps reinsertion and scar process may provide for the joint stability in a low-demanding patient. 3D printing and VR approaches in clinical practice can be useful in the management of CEIs associated with an important bone and soft tissue loss. How to cite this article Facco G, Politano R, Marchesini A, et al. A Peculiar Case of Open Complex Elbow Injury with Critical Bone Loss, Triceps Reinsertion, and Scar Tissue might Provide for Elbow Stability? Strategies Trauma Limb Reconstr 2021;16(1):53–59.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Background: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation. Objective: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy. Methods: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line. Results: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases. Conclusions: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile, The author(s) would like to thank the Spanish Association of Gastroenterology (AEG) for providing the electronic case report form service free of charge. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was promoted and funded by the European Helicobacterand Microbiota Study Group, and received support from the Spanish Association of Gastroenterology (AEG) and the Centro de Investigación Biomedica en Red de Enfermedades Hepaticas y Digestivas

Background: Bismuth quadruple (BQT) and non-bismuth quadruple (N-BQT) therapies are the recommended first-line treatments for Helicobacter (H.) pylori infection. Objective: To compare the efficacy of BQT and N-BQT in clinical practice in an area with high clarithromycin resistance, choosing the regimen on the basis of previous exposure to clarithromycin. Methods: A total of 404 consecutive Hpylori-positive, naïve patients were enrolled. A total of 203 patients without previous exposure to clarithromycin received N-BQT, 100 patients for 10days and 103 for 14days, whereas 201 with previous exposure to clarithromycin received 10-day BQT. Efficacy and treatment-related adverse events were assessed. Results and Conclusions: Eradication rates by intention-to-treat analysis were 88.2% for N-BQT and 91.5% for BQT (P=.26); per-protocol analysis eradication rates were 91.2% and 95.8% for N-BQT and BQT, respectively (P=.07). Eradication rates were significantly higher with 14-day than 10-day CT (P&nbsp

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI and is the only inhibitor with activity against T3151 mutation. The impact of ponatinib on cardiovascular events was first evaluated in the PACE trial. We therefore report and discuss most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. Though many exams can be used for diagnosis and follow-up of this kind of cardiotoxicity, echocardiography seems to have a pivotal role thanks to its feasibility, availability, and low cost.

Nowadays, the nonalcoholic fatty liver disease represents the main chronic liver disease in the Western countries, and the correct medical therapy remains a big question for the scientific community. The aim of our study was to evaluate the effect derived from the administration for six months of silybin with vitamin D and vitamin E (RealSIL 100D®) on metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease markers in nonalcoholic fatty liver disease patients. We enrolled 90 consecutive patients with histological diagnosis of nonalcoholic fatty liver disease and 60 patients with diagnosis of reflux disease (not in therapy) as healthy controls. The nonalcoholic fatty liver disease patients were randomized into two groups: treated (60 patients) and not treated (30 patients). We performed a nutritional assessment and evaluated clinical parameters, routine home tests, the homeostatic model assessment of insulin resistance, NAFLD fibrosis score and fibrosis-4, transient elastography and controlled attenuation parameter, thiobarbituric acid reactive substances, tumor necrosis factor α, transforming growth factor β, interleukin-18 and interleukin-22, matrix metalloproteinase 2, epidermal growth factor receptor, insulin growth factor-II, cluster of differentiation-44, high mobility group box-1, and Endocan. Compared to the healthy controls, the nonalcoholic fatty liver disease patients had statistically significant differences for almost all parameters evaluated at baseline (p<0.05). Six months after the baseline, the proportion of nonalcoholic fatty liver disease patients treated that underwent a statistically significant improvement in metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease was greater than not treated nonalcoholic fatty liver disease patients (p<0.05). Even more relevant results were obtained for the same parameters by analyzing patients with a concomitant diagnosis of metabolic syndrome (p<0.001). The benefit that derives from the use of RealSIL 100D could derive from the action on more systems able to advance the pathology above all in that subset of patients suffering from concomitant metabolic syndrome.

Background: SMA1 natural history is characterized by early development of chronic respiratory failure. Respiratory interventions in type 1 SMA infants are subject to great practice variability. Nusinersen, has been recently approved in Argentina. The advent of novel treatments has highlighted the need for natural history studies reporting disease progression in type 1 SMA. Objective: To analyze the progression, respiratory interventions and survival based on the type of respiratory support in type 1SMA patients, in a third level pediatric hospital in Argentina. Methods: Cohort of SMA1 patients followed at the Interdisciplinary Program for the Study and Care of Neuromuscular Patients (IPNM). Patient survival was analyzed by using the Kaplan-Meier method. Log-rank test was performed to compare the survival curve for three respiratory intervention groups. Results: 59 patients. Mean age of symptom onset was 2.19 (±1.4) months, age at diagnosis was 3.9 (±2.1) months. Patients developed respiratory failure at 5.82 months (±2.32) and 13.8 months (±5.6) in Type 1B and Type 1C, respectively (p

PRECIS An older age, a low number of baseline glaucoma medications, an early glaucoma stage, lower intraocular pressure (IOP) values during the first postoperative month, and combined surgery are possible predictors of unqualified success after a trabecular by-pass microinvasive glaucoma surgery (MIGS) procedure. PURPOSE The purpose of this study was to identify the potential predictors of unqualified success (IOP

Outflow tract (OT) premature ventricular contractions (PVCs) are commonly found in clinical practice; in most cases, PVCs are benign and observed in structurally normal hearts, not requiring any therapeutic intervention. In this study, we therefore sought to evaluate with cardiac magnetic resonance (CMR) patients with PVC and apparently normal heart at echocardiographic examination, in order to identify possible substrates linked with higher prevalence of arrhythmias or structural heart disease. Thirty-three consecutive patients with frequent PVCs originating from the ventricular OT (right and left) were enrolled in the study and assessed by echocardiography and CMR. All patients had normal baseline electrocardiogram. CMR showed structural changes in 5 patients out of 33; in 3 cases, areas of fibrosis limited in one case to the middle basal segments of the interventricular septum and in two patients to the middle basal segments of the inferior-lateral wall were found. In 2 other cases, however, late gadolinium enhancement showed significant anomalies characterized in one patient by extensive areas of subepicardial fibrosis of the left ventricle, suitable with arrhythmogenic left dominant dysplasia; in another patient, a marked trabeculation of left ventricular medium apical segments suitable with non-compaction myocardium was present. CMR may identify cases of structural heart disease in subjects with OT PVCs and apparently normal electrocardiogram and echocardiogram examinations. A preliminary screening with CMR may be considered before any further invasive electrophysiology assessment and therapeutic planning.

Background and aim: Bismuth quadruple therapy (BQT) or non-bismuth quadruple therapy (i.e., concomitant therapy) (CT) is the first-line regimens to eradicate H. pylori infection in areas with high prevalence of clarithromycin (CLA) resistance. Guidelines suggest that in areas of high prevalence of H. pylori strains with double resistance (i.e., CLA + metronidazole), BQT should be preferred to CT. The aim of this study was to evaluate the efficacy and safety of BQT administered through the three-in-one pill (Pylera) formulation in a large series of H. pylori–infected patients, naive to treatment in a region with high CLA and dual resistance.Patients and methods: We treated 250 patients (148 F and 102 M, mean age 48.6 years) with H. pylori infection naïve to treatment. Patients received esomeprazole 40 mg bid and Pylera 3 tablets qid for 10 days. Diagnosis of H. pylori infection was through 13C urea breath test (13C UBT), or stool antigen test or histology, as appropriate. The evaluation of eradication was through 13C UBT at least 45 days after the end of therapy. Incidence of treatment-related adverse events (TRAEs) was assessed through a questionnaire at the end of treatment. Compliance was considered good if at least 90% of medication had been taken. Statistical analysis was per intention-to-treat e per protocol (PP). 95% confidence intervals (CIs) were calculated.Results: 1) 13 patients (5.2%) discontinued therapy due to side effects; 2) eradication rates in ITT and PP were 227/250 (90.8%; 95% CI 86.3–93.7%) and 226/237 (95.3%; 95% CI 91–99%), respectively; 3) the prevalence of TRAEs was 26.8%; and 4) adherence to treatment was good with compliance greater than 90%.Conclusion: In this real-life study, we demonstrate that in an area with a high prevalence of H. pylori strains with CLA or CLA + metronidazole resistance, BQT using Pylera is an effective therapeutic strategy with ITT eradication rates higher than 90%; this therapy is associated with good compliance and low incidence of side effects.

Statins could increase the effectiveness of Helicobacter pylori eradication therapies due to their anti-inflammatory effect. The aim of this study was to analyze the impact of this therapeutic association in real life. This is a multicenter, prospective, non-interventional study aimed at evaluating the management of H. pylori by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap from 2013 to 2020. The association between statin use and H. pylori eradication effectiveness was evaluated through multivariate analysis. Overall, 9988 and 705 patients received empirical and culture-guided treatment, respectively. Overall, statin use was associated with higher effectiveness in the empirical group (OR = 1.3, 95%CI = 1.1–1.5), but no association was found with first-line treatment effectiveness (N = 7738), as an exception, statin use was specifically associated with lower effectiveness of standard triple therapy (OR = 0.76, 95%CI = 0.59–0.99). In the rescue therapy empirical group (N = 2228), statins were associated with higher overall effectiveness (OR = 1.9, 95%CI = 1.4–2.6). However, sub-analyses by treatment schemes only confirmed this association for the single-capsule bismuth quadruple therapy (OR = 2.8, 95%CI = 1.3–5.7). No consistent association was found between statin use and H. pylori therapy effectiveness. Therefore, the addition of statins to the usual H. pylori treatment cannot be currently recommended to improve cure rates.

Background: Bacterial antibiotic resistance changes over time depending on multiple factors, therefore, it is essential to monitor the susceptibility trends to reduce the resistance impact on the effectiveness of various treatments. Objective: To conduct a time-trend analysis of Helicobacter pylori resistance to antibiotics in Europe. Methods: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020. Results: Overall, 41,562 patients were included in the Hp-EuReg. Culture and antimicrobial susceptibility testing were performed on gastric biopsies of 3974 (9.5%) patients, of whom 2852 (7%) were naive cases included for analysis. The number of positive cultures decreased by 35% from the period 2013–2016 to 2017–2020. Concerning naïve patients, no antibiotic resistance was found in 48% of the cases. The most frequent resistances were reported against metronidazole (30%), clarithromycin (25%), and levofloxacin (20%), whereas resistances to tetracycline and amoxicillin were below 1%. Dual and triple resistances were found in 13% and 6% of the cases, respectively. A decrease (p &lt, 0.001) in the metronidazole resistance rate was observed between the 2013–2016 (33%) and 2017–2020 (24%) periods. Conclusion: Culture and antimicrobial susceptibility testing for Helicobacter pylori are scarcely performed (&lt, 10%) in Europe. In naïve patients, Helicobacter pylori resistance to clarithromycin remained above 15% throughout the period 2013–2020 and resistance to levofloxacin, as well as dual or triple resistances, were high. A progressive decrease in metronidazole resistance was observed.

Randomized clinical trials are considered the milestones of clinical research in oncology, and guided the development and approval of new compounds so far. In the last few years, however, molecular and genomic profiling led to a change of paradigm in therapeutic algorithms of many cancer types, with the spread of different biomarker-driven therapies (or targeted therapies). This scenario of “personalized medicine” revolutionized therapeutic strategies and the methodology of the supporting clinical research. New clinical trial designs are emerging to answer to the unmet clinical needs related to the development of these targeted therapies, overcoming the “classical” structure of randomized studies. Innovative trial designs able to evaluate more than one treatment in the same group of patients or many groups of patients with the same treatment (or both) are emerging as a possible future standard in clinical trial methodology. These are identified as “master protocols”, and include umbrella, basket and platform trials. In this review, we described the main characteristics of these new trial designs, focusing on the opportunities and limitations of their use in the era of personalized medicine.

Background: Intensive care unit acquired weakness (ICUAW), embraces an array of disorders labeled “critical illness polyneuropathy” (CIP), “critical illness myopathy” (CIM) or “critical illness polyneuromyopathy” (CIPNM). Several studies have addressed the various characteristics of CIPNM, but the recovery is still unclear. Objective: The present review investigated the recovery and the long-term functional outcome of subjects with CIPNM, whether the types of CIPNM have different outcomes and whether there is any supporting evidence. Methods: Literature search was performed from MEDLINE/PubMed, CINAHL, EMBASE, PeDro, Web of Science and Scopus. Inclusion criteria were: i) sample size including five or more subjects; ii) subjects who suffered from CIPNM and/or CIP, CIM and CIP/CIM; iii) CIPNM ascertained by EMG. Follow-ups longer than one year were defined as long-term.Results: Twenty-nine studies met the inclusion criteria. In total, 788 subjects with CIPNM were enrolled: 159 (20.1%) died and 588 (74.6%) were followed. Of all the included patients, 613 (77.7%) had CIP, 82 (10.4%) CIM and 56 (7.1%) CIP/CIM. Overall, 70.3% of the subjects with CIPNM fully recovered. Seven (24.1%) studies had a follow-up longer than 1 year (range 2-8) with 173 (21.9%) subjects enrolled globally and 108 followed. Of these subjects, 88.8% gained full recovery. Most of the studies did not use proper functional scales and only 4 and 3 studies employed the Barthel scale and the FIM scale. Differentiation between the types of CIPNM was performed in 7 studies, but only 3 studies reported that subjects with CIM had a better prognosis and earlier recovery than subjects with CIP/CIM.Conclusions: Subjects with CIPNM could achieve good recovery and could further improve at follow-up. The quality of the published studies due to short follow-ups and the paucity of defined outcome measures limit the evidence.

BACKGROUND: Managing Helicobacter pylori infection requires constant decision making, and each decision is open to possible errors. AIM: The aim was to evaluate common mistakes in the eradication of H. pylori, based on the "European Registry on Helicobacter pylori management". METHODS: European Registry on Helicobacter pylori management is an international multicentre prospective noninterventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. RESULTS: Countries recruiting more than 1000 patients were included (26,340 patients). The most common mistakes (percentages) were: (1) To use the standard triple therapy where it is ineffective (46%). (2) To prescribe eradication therapy for only 7 to 10 days (69%). (3) To use a low dose of proton pump inhibitors (48%). (4) In patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and metronidazole (38%). (5) To repeat certain antibiotics after eradication failure (>15%). (6) Failing to consider the importance of compliance with treatment (2%). (7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines. CONCLUSION: The management of H. pylori infection by some European gastroenterologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.

Aim The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor–positive (HR+) tumours. Patients and methods In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and were randomly assigned (1:1:1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis. Results With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4%, 93.2% and 93.3% with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95% confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95% CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95% CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3%, 7.3% and 16.6% patients, and in the safety population, grade 3–4 side-effects were reported in 4.2%, 6.9% and 9.1% patients treated with T, L or ZL, respectively. Conclusion HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. ( NCT00412022 )

BACKGROUND Urotensin II (U-II) is a vasoactive peptide that interacts with a specific receptor named UTR. Recently, our group has demonstrated increased UTR expression in both human colon adenocarcinoma cell lines and adenomatous polyps, as well as in colon carcinoma samples if compared to healthy colon samples of the same patients. We also showed that an UTR agonist induced an increase in colon adenocarcinoma cell growth in vitro, whereas the UTR block with a specific antagonist caused an inhibition of their growth and an inhibition of about 50% of both motility and cell invasion. Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) associated with an increased baseline risk for colon cancer compared with the general population, and this risk is mostly attributed to chronic inflammation and immune dysregulation. This risk increases along with the duration of the disease, as demonstrated by many studies. There are no UTR expression data related to UC, and we therefore evaluated UTR expression in ill colon biopsies and in healthy colon ones of patients with UC and colon biopsies of healthy patients. METHODS We enrolled, prior to informed consent, 11 patients (5 males and 6 females, age range 29-75 years, median age 52 years) with first UC diagnosis compared to 11 healthy controls (6 males and 5 females, age range 30-78 years, median age 55 years). We have therefore sampled inflammatory and healthy tissue in UC patients. We have also taken colic tissue samples in healthy subjects. Evaluation of receptor expression was performed by reverse transcription-polymerase chain reaction (RT-PCR), Western Blot analysis. The ANOVA Test (P

Introduction: Irritable bowel syndrome represents one of the most difficult gastroenterological diseases to treat, that usually induces the patients to follow different drug therapies, often not useful in symptom control. In this scenario low FODMAP diet could have positive effects in patients with irritable bowel syndrome, even because this type of diet regimen is characterized by a low gluten amount due to the exclusion of cereals. Methods: We enrolled 120 patients with irritable bowel syndrome, according to the Rome IV criteria, who were referred to Hepatogastroenterology Division of the University of Campania L. Vanvitelli from June to December 2018. They underwent a low FODMAP diet for six weeks, followed by a gradual weekly reintroduction of every category of food for three months. The patients had a follow-up evaluation for six months after the end of food reintroduction period. We measured abdominal pain with subjective numerical scale from 0 to 10. We evaluated other gastrointestinal symptoms with a questionnaire about symptoms of lower digestive tract, evaluating their frequency and intensity. We also evaluated the impact of irritable bowel syndrome on daily life with neurological bowel dysfunction score. Results: We obtained a good patient-adherence to diet and a statistically significant decrease of abdominal pain, bloating, flatulence, diarrhea, constipation, and neurological bowel dysfunction score (p &lt, 0.001) at the end of the diet. These results remained constant in the follow-up period. Conclusions: We recommend the use of a low FODMAP diet regimen in patients with irritable bowel syndrome in order to control the symptoms and improve the quality of life.

Background Percutaneous Endoscopic Gastrostomy (PEG) can involve some complications, despite the good safety of its track record. The Buried Bumper Syndrome (BBS) is a rare, late and dangerous complication that consists in the erosion of the internal bumper through the gastric wall. Case presentation We report the development of BBS in a man with chronic obstructive pulmonary disease (COPD) who had a persistent chronic cough which was prevalently but not solely in the morning and required placement of a PEG tube for continuous infusion of Levodopa/carbidopa intestinal gel for advanced Parkinson's disease. Conclusion We believe that COPD with chronic cough while not representing an absolute contraindication to PEG placement, may potentially cause BBS and therefore an appropriate regimen of tube care by expert personnel is mandatory in this setting.

Importance: Clinical severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection seems to be lower in children compared to that in adults. Defining the pathophysiological mechanisms of such disease patterns maybe relevant for development of effective public health strategies. It has been hypothesised that the lower severity of SARS-CoV-2 infection in children could be due to the differential expression of angiotensin-converting enzyme 2 (ACE2), which serves as a virus receptor. Objective: To evaluate the expression of ACE2, ACE1, and TMPRSS2 genes at the level of the two most relevant entry sites for SARS-CoV-2, the upper respiratory tract and small intestine, in healthy children and adult subjects. Design, Setting, and Participants: This prospective study included healthy individuals of both sexes, aged 1-10 years in the paediatric population (n=30) and 20-80 years in the adult population (n=30). The participants were consecutively evaluated at two tertiary centres for paediatrics, gastroenterology, and otolaryngology. Main Measures: Expression of ACE2, ACE1, and TMPRSS2 genes in samples collected from the upper respiratory tract and small intestine. Results: We found no difference in ACE2, ACE1, and TMPRSS2 expression in the nasal epithelium between children and adult subjects. ACE2 expression was more abundant in the small intestine of children compared to that in adults. ACE1 expression was higher in the small intestine of adults compared to that in children. Intestinal TMPRSS2 expression was similar in the two study populations. Conclusions and Relevance: The general lower severity of SARS-CoV-2 infection in children does not seem to be related to a lower expression of ACE2 and/or TMPRSS2 in the respiratory tract or in the gastrointestinal tract. Other co-factors may confer protection against SARS-CoV-2 in children. The exploration of such factors is of pivotal importance for development of innovative protective strategies against SARS-CoV-2. Funding Statement: This work was supported in part by a grant of Regione Campania POR FESR 2014/2020, Task Force Covid-19 DGR 140 – 17 March 2020. Declaration of Interests: The authors have no other conflict of interests that are directly relevant to the content of this manuscript, which remains their sole responsibility. Ethics Approval Statement: The study was approved by the Ethics Committee of the University Federico II of Naples, Italy. Written informed consent was obtained from the adult participants and from the parents/tutors of minors.

Introduction: Bisphenol A (BPA) exposure has been correlated to non-alcoholic fatty liver disease (NAFLD) development and progression. We investigated, in a clinical model, the effects of the administration of 303 mg of silybin phospholipids complex, 10 g of vitamin D, and 15 mg of vitamin E (RealSIL, 100D, IBI-Lorenzini, Aprilia, Italy) in male NAFLD patients exposed to BPA on metabolic, hormonal, and oxidative stress-related parameters. Methods: We enrolled 32 male patients with histologic diagnosis of NAFLD and treated them with Realsil 100D twice a day for six months. We performed at baseline clinical, biochemical, and food consumption assessments as well as the evaluation of physical exercise, thiobarbituric acid reactive substances (TBARS), plasmatic and urinary BPA and estrogen levels. The results obtained were compared with those of healthy control subjects and, in the NAFLD group, between baseline and the end of treatment. Results: A direct proportionality between TBARS levels and BPA exposure was shown (p &lt, 0.0001). The therapy determined a reduction of TBARS levels (p = 0.011), an improvement of alanine aminotransferase, aspartate aminotransferase, insulinemia, homeostatic model assessment insulin resistance, C reactive protein, tumor necrosis factor alpha (p &lt, 0.05), an increase of conjugated BPA urine amount, and a reduction of its free form (p &lt, 0.0001, p = 0.0002). Moreover, the therapy caused an increase of plasmatic levels of the native form of estrogens (p = 0.03). Conclusions: We highlighted the potential role of BPA in estrogen oxidation and oxidative stress in NAFLD patients. The use of Realsil 100D could contribute to fast BPA detoxification and to improve cellular antioxidant power, defending the integrity of biological estrogen-dependent pathways.

Helicobacter pylori (H. pylori ) infection is very common and affects approximately half of the world population. It causes gastric diseases, but some authors have reported an association of H. pylori infection with other systemic manifestations beginning in 1994. The list of potential effects of H. pylori outside the stomach includes a number of extragastric manifestations and we focused on neurological, dermatological, hematologic, ocular, cardiovascular, metabolic, allergic, and hepatobiliary diseases. This review discusses these important reported manifestations that are not related to the gastrointestinal tract.

International audience; 5548 Background: Ovarian cancer is the leading cause of death by gynecological cancer. Complete surgery remains one of the main prognostic factors. Laparoscopic exploration is mandatory to assess surgical resectability at diagnosis or after neoadjuvant chemotherapy. However, there is no clinical or biological marker that can correctly predict resectability and may be able to avoid a second laparoscopic exploration for initially unresectable diseases. Our aim was to assess circulating tumor DNA (ctDNA) value as a predictive non-invasive marker of evolution towards resectability for patients with epithelial ovarian cancer receiving first-line chemotherapy. Methods: We explored in this work one of the secondary objectives of the CIDOC study (NCT03302884). CIDOC is a multicenter prospective study aiming to explore ctDNA value as early marker of disease relapse after first-line treatment for epithelial ovarian cancer. Patients with mucinous histology or early stages not requiring chemotherapy are excluded. Plasma samples are collected at diagnosis, during neoadjuvant chemotherapy, and during follow-up. After DNA extraction, panel-based next generation sequencing is performed on both tumor samples and germline DNA, and somatic mutations of interest are selected for ctDNA monitoring. ctDNA analyses are conducted using droplet digital PCR (BioRad QX200) by measuring the variant allele fraction (VAF) of previously identified mutations. Results: This intermediary analysis has included 47 patients diagnosed between March 2017 and December 2019. Median age was 69 years old (48 – 84). Most of the patients had advanced disease (89.4% stage FIGO III or IV), serous histology (94.8%), and high grade tumor (92.3%). Most of the patients underwent complete interval cytoreductive surgery (76.3% vs 17.4% complete upfront surgery). Most of the tumors had TP53 mutations (85.1%), following by alterations involving DNA repair genes (38.3%). Median cell-free DNA concentration at baseline was 0.38 ng/µL (0 – 12.8). ctDNA was identified in 92.1% of patients at baseline with a median VAF of 1.84% (0 – 42.52%). ctDNA VAF was correlated to the peritoneal dissemination ( p= 0.039) assessed with the peritoneal cancer index. ctDNA clearance after preoperative chemotherapy tended to be correlated to achievement of complete interval surgery for patients receiving neoadjuvant chemotherapy ( p= 0.108). Conclusions: ctDNA may be a promising non-invasive marker to assess peritoneal cancer spreading and to predict surgical resectability after neoadjuvant chemotherapy. If confirmed in larger populations, this may enable to avoid additional surgical explorations for patients who remain ctDNA positive after chemotherapy. Clinical trial information: NCT03302884.

Background: Colorectal cancer is one of the most common tumors for both men and women: in the United States, it represents the third leading cause of new cancer cases and cancer-related deaths. The prognosis is directly related to tumor infiltration in the mesorectum and lymph node metastases. In particular, it’s important to define the distance between lymphadenopathy and mesorectal fascia, as this has repercussions on surgical planning. This study aimed to evaluate the agreement among observers with different abdominal MRI expertise and intra-observer reliability in lymph nodes size and feature definition. Methods: In this retrospective study, MRI examinations were performed in 88 patients with rectal adenocarcinoma treated with primary surgery. Four observers, two senior physicians, and two junior physicians, analyzed MRI scans in two sessions 30 days apart and determined the size and morphological pattern of regional lymph nodes. Statistical analysis included the determination of Fleiss kappa (k) coefficient, Cohen's Kappa coefficient, and confidence intervals (CI). Results: The inter-observer reproducibility for MRI N-staging was good among the four physicians (kappa = 0.65; CI 0.45–0.77). Reproducibility between the two senior physicians had a kappa of 0.68 (CI 0.62–1.00), while between the two junior physicians had a kappa of 0.61 (CI 0.33–0.89). Inter-observer reproducibility was excellent for mesorectal, inferior mesenteric, and internal iliac lymph nodes (kappa values of 0.89, 0.82, and 0.80 respectively). For the other two nodal stations (superior and middle rectal lymph nodes, sacral lymph nodes), there was a good interobserver reproducibility (kappa between 0.70 and 0.77).The intra-observer reproducibility of interpretations of the MRI overall N staging progressively decreased among observer B (kappa= 0.85), observer C (kappa= 0.59), and the other two physicians. There was a significant difference in lymph nodes measurements between the first and second sessions in observer A (p ≥ 0.05). Excellent intraobserver reproducibility was found for mesorectal lymph nodes; the lowest intraobserver reproducibility values were found for presacral and lateral sacral lymph nodes.Conclusions: Although the low accuracy of MRI in assessing the involvement of metastatic lymph nodes in rectal cancer, this study demonstrates good interobserver reliability among physicians with different abdominal MRI experiences.

Although previous studies have shown the benefits of exercise training in hemodialysis patients, little is known about the effects of long-term of exercise program on these patients. We investigated the effects and the safety of long-term aerobic training and the effects of detraining on functional capacity and quality of life in hemodialysis patients. Ten patients were allocated to two groups: training and detraining. The training group completed at least 30 months of aerobic training, and the detraining group completed at least 20 months and then discontinued the training for at least 10 months. The outcomes were analyzed at baseline, after 3 months of aerobic training and at the 30-month follow-up. The training and detraining groups performed 37 (5.5) and 24 (3.0) months of aerobic training, respectively. The detraining group discontinued the training for 11.0 (2.0) months. After 3 months of aerobic training, six-minute walking test distance increased significantly in both groups (training group = 569 (287.8) vs 635.5 (277.0) m, p = 0.04; detraining group = 454.5 (72.3) vs 515.0 (91.8) m, p = 0.04). There was no significant difference in the six-minute walking test distance in the training group (576.5 (182.5), p > 0.05) and a significant decrease (436.2 (89.6) m, p = 0.04) in the detraining group at the follow-up compared to the third month of aerobic training. No significant difference was observed in quality of life during the study. No complications were found during the protocol of the exercise. These results suggest that long-term aerobic training is safe and can maintain functional capacity in hemodialysis patients. In contrast, detraining can result in loss of functional capacity in these patients.

We further evaluated the Performance Diagnostic Checklist- Safety (PDC-Safety) by comparing the effectiveness of a PDC-Safety indicated intervention with a PDC-Safety non-indicated intervention for...

Introduction This retrospective consecutive case series assessed 12-month effectiveness and safety of iStent® or iStent inject® trabecular micro-bypass implants with cataract surgery in patients with open-angle glaucoma (OAG) in a real-world clinical setting. Methods Effectiveness outcomes consisted of intraocular pressure (IOP) reduction; glaucoma medication reduction; proportions of eyes achieving IOP

The Absorb bioresorbable vascular scaffold (BVS) promised to avoid some of the disadvantages of its metal predecessors. Even though it has been taken off the market, limited data is available about its use in coronary chronic total occlusion (CTO) and its performance in overlap segments, which would be of special research interest due to its large thickness. This data is still pertinent since the platform of bioresorbable devices has not been abandoned, with several companies working on it. We aimed to compare healing and performance between overlap (OL) and non-overlap regions (NOL) of CTO lesions treated with BVS, using optical coherence tomography (OCT). Fourteen patients with overlapping BVS were included from the GHOST-CTO registry, resulting in 25 OL and 38 NOL regions. OCT based parameters were compared between OL and NOL groups at baseline (post-implantation) and 12-month follow-up. The mean age was 61.7 ± 7.2 years and 12 (86%) were males. Twelve (86%) patients underwent PCI for stable coronary artery disease and 2 (14%) had unstable angina. At 12-month follow-up, mean lumen area decreased in both NOL and OL regions, but the decrease was significantly larger in the OL region (NOL − 0.7 ± 1.33 vs. OL − 2.4 ± 1.54 mm2; p = 0.002). Mean scaffold area increased in both regions, but increased significantly more in NOL ( + 1.1 ± 1.54 vs. + 0.4 ± 1.16 mm2; p = 0.016). The percent of uncovered struts was lower in the OL group (5.0 ± 6.6% vs. 3.75 ± 8.7%, p = 0.043), whereas the percentage of malapposed struts was similar (0.3 ± 0.5% vs. 0.7 ± 2.3%, p = 0.441). Neointimal hyperplasia (NIH) was more pronounced in the OL region (0.13 ± 0.04 vs. 0.24 ± 0.10 mm2, p = 0.001). The OL and NOL segments showed comparable healing in terms of coverage and malapposition. However, NIH was more prominent in OL region. The long-term clinical implications of these findings needs further evaluation. The present study provides important insights for future development of BVS technology.

A obesidade está associada a várias complicações e maior risco de mortalidade. A mudança no estilo de vida é uma das intervenções fundamentais para melhora do quadro clínico desses pacientes, sendo a prática de exercícios físicos um dos seus componentes. O objetivo do presente estudo foi realizar uma revisão de literatura sobre o exercício físico em adultos e idosos com obesidade, descrevendo os principais programas de exercício, a forma adequada de prescrição e os benefícios da sua prática regular. O exercício aeróbico é a modalidade mais indicada para a perda de peso e está associado com maiores benefícios para estes pacientes. Adicionalmente, tem sido preconizado a realização de exercício resistido como terapia complementar. Para alcançar os benefícios da prática regular de exercício físico, a literatura sugere que sejam realizados exercícios aeróbicos de moderada a alta intensidade por no mínimo 150 minutos por semana e quando possível acrescentar o treinamento resistido, 2 a 3 vezes por semana, com carga de 60-70% de uma repetição máxima. Portanto, a prescrição individualizada de exercício físico para pacientes com obesidade representa uma estratégia eficaz para a redução do peso, tratamento e controle dos fatores de risco cardiovasculares, além de promover benefícios na sintomatologia e em outras complicações.

AIM To assess the efficacy and safety of the Ologen collagen matrix as an adjuvant for combined phacoemulsification and nonpenetrating deep sclerectomy (Phaco-NPDS), in addition to mitomycin C (MMC). MATERIALS AND METHODS This was a longitudinal retrospective comparative study of eyes treated with Phaco-NPDS, with (group 1) or without (group 2) an Ologen collagen matrix implant, in addition to MMC. The main outcome measures were operative success [absolute success: intraocular pressure (IOP)

Introduction In this real-world, retrospective, comparative study we evaluated 6-month performance and safety in consecutive eyes following implantation of the iStent® or iStent inject® trabecular micro-bypass device with concomitant cataract surgery. Methods Performance outcomes included intraocular pressure (IOP) reduction; glaucoma medication reduction; proportions of eyes achieving an IOP of

Atualizacao das Diretrizes em Cardiogeriatria da Sociedade Brasileira de Cardiologia – 2019

Standardized bedside rounds can improve communication and the quality of care for patients in hospitals. However, it can be challenging to change previously established provider practices to adhere to new procedures. This study evaluated 2 packaged interventions, derived from a modified Performance Diagnostic Checklist interview, to increase adherence to standardized rounding practices in 2 hospital units. Researchers observed physicians at a university hospital on rounds 2-3 times per week, and 2 phases of intervention were implemented to improve adherence. The interventions included task clarification, feedback, and weekly huddles. Compared to baseline, phases 1 and 2 of the intervention improved clinician adherence to the standardized bedside rounding checklist by 24.94% and 30.94% in unit 1 and 26.76% and 44.06% in unit 2, respectively. The standardized rounds did not require additional time following the intervention. These results indicate that physician adherence can be improved through behavioral interventions.

Background and Aims Chronic kidney disease (CKD) is a systemic condition because it modifies all organs' function due to an imbalance in plasma volume, electrolytes, hormones, and proteins. Indeed, at the nervous system level, mild cognitive impairment (MCI), sleep disorders and depression often accompany CKD. MCI partially explains the low quality of life of CKD patients, comparable to that of metastatic cancer patients. Mild Cognitive Impairment (MCI) has a high prevalence in this cohort (27-62%). Nevertheless, scattered literature data suggest that CKD patients can also have poor motor control, evidenced by a higher risk of falls, postural instability, reduced gait speed. In this cohort, few data are available regarding the motor circuits called central pattern generators, which control physiological tremor. Specifically, uraemic encephalopathy accentuates physiological tremor, which is regulated by central and peripheral oscillators. Overall, subtle changes in motor control often accompany other forms of MCI. Therefore, this study aimed at evaluating the effects of chronic kidney disease on cognitive and motor functions using up-to-date technologies to record physiological tremor and innovative data analysis. Method This retrospective case-control study enrolled 313 patients (139 controls, 79 CKD patients stage III-IV, 35 kidney transplant (Tx), 60 dialysis (HD) patients). These groups were comparable for age and weight. Creatininemia, azotemia, LDL, HDL, hemoglobin, and proteinuria were used for correlative analyses. We evaluated the chronotype using the Morningness-Eveningness Questionnaire (MEQ) and the degree of sleepiness using the Epworth Sleepiness Scale (ESS). Cognitive impairment was assessed by the Montreal Cognitive Assessment test (MoCA). Cognitive domains of the MoCA score were projected onto brain regions using CerebroViz library in R and a new transformation matrix derived from fMRI literature data. UMAP algorithm was used to identify patients' subgroups. The physiological tremor was recorded on patients maintaining the dominant arm extended using the smartphone App Phyphox. The tremor frequency spectrum was extracted by Fourier analysis. Results The sleepiness score (ESS) was significantly increased in HD (ESS = 5±0.4) compared to the healthy controls (ESS= 4±0.41) whereas was not significantly modified in CKD patients (3.24± 0.32). The chronotype was also not significantly different among the various groups. The mean score of the MoCA test was significantly lower in CKD, Tx, and HD groups (CKD MoCA =24.5±0.3; Tx MoCA =25.4±0.6; HD MoCA =24.6±0.7) than controls (MoCA score=28±0.1). A different pattern of impairment in the cognitive domains of MoCA was evidenced in the various groups using the CerebroViz projection and UMAP tools. MoCA score was inversely correlated with proteinuria (Pearson coefficient=-0.47; p The higher frequencies of the physiological tremor (11-13 Hz) were significantly more represented in Tx patients compared to controls (p Conclusion Our results suggest that CKD patients present altered cognitive and motor control patterns, linked in part to the proteinuria level, suggesting a pathogenetic role of endothelial dysfunction. The characteristic motor, sleepiness and cognitive patterns of HD patients might be due to the arteriovenous fistula or the other peculiarities of these patients. These results might help identify new early markers of brain dysfunction in these patients, with the possibility of delaying or reversing cognitive decay.

Computed tomography-guided percutaneous needle biopsy of the lung is a safe and effective procedure for removal of rustling of lung cancer in patients requiring histological diagnosis and to be able to carry out molecular biology studies, it does not require hospitalization and considerably limits the use of surgical biopsy. The purpose of our study is to assess the sensitivity and specificity of CT guided percutaneous procedure considering the best approach in order to obtain an acceptable number of withdrawals reducing patient exposure to ionizing radiation. Prior to the procedure we evaluate the best percutaneous approach studying the imaging features of the lung nodule. At the beginning of the procedure were performed a basic volumetric chest CT scan for the localization of the nodule to choose the point of access with bright laser pointer and successive CT scans of 3 cm thickness with a lowdose technique to follow the needle trajectory until the nodule of interest. Key point of this study is the use of 16-18 Gauge coaxial needle or introducer inch, to reach the target lesion; it allows multiple biopsies reducing the number of percutaneous accesses: in fact, reached the lesion, is possible to slide inside it the needle with semiautomatic shearing system of the Tru-Cut type and make multiple withdrawals. We performed 106 percutaneous CT-guided pulmonary needle biopsy on patients aged 41 to 89 years, 76 males and 30 females; in only 2 cases (1.88% of the patients) we not obtained an accurate withdrawal of bioptic specimens for histological characterization of target lesion, and in just 2 cases the development of pneumothorax required placement of percutaneous thoracic drainage. This approach has been shown to have sensitivity and specificity of 98,1% and 97,1% respectively, for a proper selection of specimens and a correct histological diagnosis. A standardized and repeatable protocol for performing CT-guided biopsies is of key importance in order to reduce patient’s exposure to ionizing radiation, to gain the highest possible number of appropriate withdrawals and to minimize procedural complications.

Background and Objectives: Laboratory liver abnormalities can be observed in patients affected with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA), especially with a cholestatic pattern. The first objective of our review article is to discuss the potential link between antimitochondrial antibodies (AMA) and/or primary biliary cholangitis (PBC) and PMR/GCA, according to the evidences of literature. The second objective is to discuss the association of PMR/GCA with the other rheumatic diseases having PBC as a common manifestation. Materials and Methods: A literature search was performed on PubMed and Medline (OVID interface) using these terms: polymyalgia rheumatica, giant cell arteritis, antimitochondrial antibodies, primary biliary cholangitis, primary Sjogren’s syndrome, systemic sclerosis, and systemic lupus erythematosus. The search was restricted to all studies and case reports published in any language. Reviews, conference abstracts, comments, and non-original articles were excluded; however, each review’s reference list was scanned for additional publications meeting this study’s aim. When papers reported data partially presented in previous articles, we referred to the most recent published data. Results and Conclusions: Our literature search highlighted that cases reporting an association between AMA, PBC and PMR/GCA were very uncommon; AMA antigenic specificity had never been detected and biopsy-proven PBC was reported only in one patient with PMR/GCA. Finally, the association of PMR/GCA with autoimmune rheumatic diseases in which PBC is relatively common was anecdotal.

Objectives To evaluate the accuracy of a new COVID‐19 prognostic score based on lung ultrasound (LUS) and previously validated variables in predicting critical illness. Methods We conducted a single‐center retrospective cohort development and internal validation study of the COVID‐19 Worsening Score (COWS), based on a combination of the previously validated COVID‐GRAM score (GRAM) variables and LUS. Adult COVID‐19 patients admitted to the emergency department (ED) were enrolled. Ten variables previously identified by GRAM, days from symptom onset, LUS findings, and peripheral oxygen saturation/fraction of inspired oxygen (P/F) ratio were analyzed. LUS score as a single predictor was assessed. We evaluated GRAM model's performance, the impact of adding LUS, and then developed a new model based on the most predictive variables. Results Among 274 COVID‐19 patients enrolled, 174 developed critical illness. The GRAM score identified 51 patients at high risk of developing critical illness and 132 at low risk. LUS score over 15 (range 0 to 36) was associated with a higher risk ratio of critical illness (RR, 2.05; 95% confidence interval [CI], 1.52‐2.77; area under the curve [AUC], 0.63; 95% CI 0.676‐0.634). The newly developed COVID‐19 Worsening Score relies on five variables to classify high‐ and low‐risk patients with an overall accuracy of 80% and negative predictive value of 93% (95% CI, 87%‐98%). Patients scoring more than 0.183 on COWS showed a RR of developing critical illness of 8.07 (95% CI, 4.97‐11.1). Conclusions COWS accurately identify patients who are unlikely to need intensive care unit (ICU) admission, preserving resources for the remaining high‐risk patients.