Search

Objectives: Despite the large amount of literature examining the potential influence of subthalamic nucleus deep brain stimulation (STN-DBS) on psychiatric symptoms and cognitive disorders, only a few studies have focused on its effect on personality. We investigated the correlation between total electrical energy delivered (TEED) and the occurrence of depressive traits in patients with Parkinson disease (PD) after one year of DBS. Materials and Methods: Our study involved 20 patients with PD (12 women, mean [±SD] age 57.60 ± 7.63 years) who underwent bilateral STN-DBS, whose personality characteristics were assessed using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), according to the core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD) procedure. Results: We found that despite a marked improvement in motor functions and quality of life after 12 months, patients showed a significant increase in MMPI-2 subscales for depression (D scale and Depression scale) and in other content component scales (low self-esteem, work interference, and negative treatment indicators). Interestingly, only the TEED on the right side was inversely correlated with the changes in scale D (rs = −0.681, p = 0.007), whereas depressive traits did not correlate with disease duration, levodopa equivalent daily dose (LEDD) reduction, patient's age, or severity of motor symptoms. Conclusions: Our preliminary observations indicate that despite the excellent motor outcome and general improvement in quality of life, DBS treatment can result in patients poorly adjusting to their personal, familiar, and socio-professional life. Different influences and multiple factors (such as TEED, intra/postsurgical procedure, coping mechanisms, and outcome expectations) may affect depressive traits. Further advances are expected to improve stimulation methods.

Several electrocardiogram (ECG) criteria have been proposed to predict the location of the culprit occlusion in specific subsets of patients presenting with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to develop, through an independent validation of currently available criteria, a comprehensive and easy-to-use ECG algorithm, and to test its diagnostic performance in real-world clinical practice.We analyzed ECG and angiographic data from 419 consecutive STEMI patients submitted to primary percutaneous coronary intervention over a one-year period, dividing the overall population into derivation (314 patients) and validation (105 patients) cohorts. In the derivation cohort, we tested60 previously published ECG criteria, using the decision-tree analysis to develop the algorithm that would best predict the infarct-related artery (IRA) and its occlusion level. We further assessed the new algorithm diagnostic performance in the validation cohort.In the derivation cohort, the algorithm correctly predicted the IRA in 88% of cases and both the IRA and its occlusion level (proximal vs mid-distal) in 71% of cases. When applied to the validation cohort, the algorithm resulted in 88% and 67% diagnostic accuracies, respectively. In a real-world comparative test, the algorithm performed significantly better than expert physicians in identifying the site of the culprit occlusion (P = .026 vs best cardiologist and P.001 vs best emergency medicine doctor).Derived from an extensive literature review, this comprehensive and easy-to-use ECG algorithm can accurately predict the IRA and its occlusion level in all-comers STEMI patients.

(1) Background: Neuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) represents a diagnostic and therapeutic challenge in neurosurgical practice, expanding the burden of care and exposing patients to additional risks related to further invasive procedures and treatment delays. In addition, atypical cases and overlapping features have not been entirely addressed by modern diagnostic research. The aim of this study was to validate a previously designed and internally validated ResNet101 deep learning model to differentiate glioblastomas, PCNSLs and BMs. (2) Methods: We enrolled 126 patients (glioblastoma: n = 64; PCNSL: n = 27; BM: n = 35) with preoperative T1Gd-MRI scans and histopathological confirmation. Each lesion was segmented, and all regions of interest were exported in a DICOM dataset. A pre-trained ResNet101 deep neural network model implemented in a previous work on 121 patients was externally validated on the current cohort to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans. (3) Results: The model achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.73; 95%CI: 0.62–0.85), glioblastomas (AUC: 0.78; 95%CI: 0.71–0.87) and moderate to low ability in differentiating BMs (AUC: 0.63; 95%CI: 0.52–0.76). The performance of expert neuro-radiologists on conventional plus advanced MR imaging, assessed by retrospectively reviewing the diagnostic reports of the selected cohort of patients, was found superior in accuracy for BMs (89.69%) and not inferior for PCNSL (82.90%) and glioblastomas (84.09%). (4) Conclusions: We investigated whether the previously published deep learning model was generalizable to an external population recruited at a different institution—this validation confirmed the consistency of the model and laid the groundwork for future clinical applications in brain tumour classification. This artificial intelligence-based model might represent a valuable educational resource and, if largely replicated on prospective data, help physicians differentiate glioblastomas, PCNSL and solitary BMs, especially in settings with limited resources.

Background and aim Measurement of cardiac index (CI) is crucial in the hemodynamic assessment of critically ill patients in the intensive care unit (ICU). The most reliable trans-thoracic echocardiography (TTE) technique for CI estimation is the left ventricular outflow tract (LVOT) Doppler method that requires, among other parameters, the LVOT cross-sectional area (CSA) measurement. However, geometrical assumptions inherent limitations and practical disadvantages related to the ICU setting, hamper LVOT-CSA assessment. In this study, we aimed to validate a simplified formula, leveraging only on LVOT-velocity time integral (VTI) and heart rate (HR) variables, for the non-invasive estimation of CI in ICU patients. Methods and Results We prospectively enrolled 50 consecutive patients admitted to our ICU requiring PAC over a one-year period. For each patient we measured the CI by PAC (CIPAC) and TTE. The latter was obtained both with the “traditional formula” (traditional CITTE), requiring LVOT-CSA assessment, and our new “simplified formula” (simplified CITTE). The correlation between the simplified CITTE and CIPAC was strong (r = 0.81) and resulted significantly greater than the traditional CITTE and CIPAC correlation (r = 0.70; p < 0.05 for Pearson r coefficients comparison). Both TTE-based CI showed an acceptable agreement (+0.19±0.48 L/min/m2 for simplified CITTE and -0.18±0.58 L/min/m2 for traditional CITTE) with the reference CIPAC. Conclusion In this study, we propose an easy-to-use and practical approach, leveraging on TTE LVOT-VTI and HR only, for non-invasive estimation of CI in ICU patients.

Introduction: The disease caused by the SARS-CoV-2 virus (COVID-19) frequently leads to serious complications and prolonged hospitalizations requiring effective care after discharge. Aim of the study: Aim of this study was to identify feasible and cost-effective predictors of outcome among clinical characteristics, functional status, laboratory, echocardiographic and lung ultrasound data of COVID-19 patients. Material and methods: Patients affected by COVID-19 who experienced a prolonged hospitalization due to a severe form of the disease and that have been discharged from the COVID-19 rehabilitation unit (RU) were prospectively enrolled between April 6th and May 22nd, 2020. All the patients underwent a 6-minute walk test (6MWT) at the 30-day follow-up. Baseline characteristics, laboratory, functional exercise tests, echocardiographic and lung ultrasound (LUS) data collected between hospitalization, admission to RU, discharge from RU and follow-up were compared. Correlations with the predicted distance covered at the 6MWT (6MWD) were made. Results: 40 patients met inclusion criteria and presented to follow-up (13 women [32.5%] and 27 men [67.5%]; mean age 66 ± 10 years). Among all variables analysed, only functional tests at discharge showed a remarkable correlation with the 6MWD. Significant improvement in lung ultrasound score (LUSS) was also observed however without correlation with 6MWD. Conclusions: functional tests at discharge from RU identified patients with different 30-day outcomes that could deserve a stricter long-term follow-up. This may help in planning a personalized follow-up. The costs and effort were minimal. The severity of the acute phase did not significantly influence functional recovery. LUS was useful to identify subclinical lung damage and its evolution over time, however without clear functional correlation.

Measurement of cardiac index (CI) is crucial in the hemodynamic assessment of critically ill patients in the intensive care unit (ICU). The most reliable trans-thoracic echocardiography (TTE) technique for CI estimation is the left ventricular outflow tract (LVOT) Doppler method that requires, among other parameters, the LVOT cross-sectional area (CSA) measurement. However, inherent and practical disadvantages, mostly related to the ICU setting, hamper LVOT-CSA assessment. In this study, we aimed to validate a simplified formula, leveraging on LVOT-velocity time integral (VTI) and heart rate (HR) only, for non-invasive estimation of CI in ICU patients.We prospectively enrolled 50 consecutive patients admitted to our ICU requiring pulmonary artery catheterization (PAC) over a one-year period. For each patient we measured the CI by PAC (CIIn this study, we validated a practical approach, leveraging on TTE LVOT-VTI and HR only, for non-invasive estimation of CI in ICU patients.

Objective This study aims to assess the feasibility and reliability of our endoscopic trans-nasal technique for the repair of cribriform and sellar high-flow cerebrospinal fluid (CSF) leaks. Methods A comparison between patients suffering from high-flow rhinorrhea and treated through a free grafting endoscopic technique or the “parachute” technique, our nasal packing proposal, was performed. Results Thirty-three patients were included. The mean age was 52 years (range: 36–68 years). The etiology of the CSF leaks was iatrogenic in 16 cases (48.5%), traumatic in 5 cases (15.2%), spontaneous in 11 cases (33.3%), and related to anterior skull base tumors in 1 case (3%). The bone defect affected the sphenoidal sinus in 20 cases (60.6%), the cribriform plate of the ethmoid in 10 cases (30.3%), and both the sphenoid and ethmoid in 3 cases (9.1%). The mean size of bone defects was 8.5 ± 3.9 mm. The median follow-up was 28 (64) months. A CSF leak recurrence occurred in no cases treated with the parachute technique and in 3 cases that underwent conventional endoscopic treatments. The CSF leak recurrences were associated with 2 iatrogenic and 1 post-traumatic fistula. All the CSF leak recurrences underwent the parachute technique, not showing second recurrences. Conclusions Our results suggest that the parachute technique is simple, safe, and effective. We recommend it as an alternative treatment to vascular flaps for the treatment of high-flow and recurrent fistulas.

During transcatheter edge-to-edge repair (TEER), the reduction of functional mitral regurgitation (FMR) severity, compared with baseline evaluation, is not uncommon. Because the procedural strategies are mainly guided by the location and severity of the regurgitant jets, intraprocedural downgrading (ID) of regurgitation severity could affect the procedural strategy and the results. The aim of this study was to evaluate the prevalence of ID during TEER and to compare early and midterm outcomes in patients with and without ID. All patients with moderate-to-severe or severe FMR who underwent TEER in San Raffaele Hospital between 2018 and 2020 were evaluated in this single-center, retrospective study. ID was defined as mild (1+) or moderate (2+) regurgitation degree during intraprocedural evaluation. The outcomes, assessed at discharge and at 2 years of follow-up, were all-cause mortality, heart failure hospitalization, and recurrence of mitral regurgitation2+. The final study cohort included 55 patients: 42% presented with ID. At discharge, 85.5% of patients achieved regurgitation reduction to 2+ or less: 100% in patients with ID versus 75% in patients without ID, p0.009. At 2 years, no significant difference in the incidence of all-cause mortality, heart failure hospitalization, and the recurrence of mitral regurgitation2+ between patients with ID or without ID was found. In conclusion, ID is frequent during TEER in FMR. No baseline characteristics were found to identify this group of patients. In patients with ID, the combination of live intraprocedural imaging and baseline ambulatory assessment of regurgitant jets seems effective in the procedural guiding to achieve a successful and durable mitral repair.

Myocardial fibrosis is a remarkably dynamic process mediated by different molecular pathways that represent potential targets of novel therapeutic interventions. Transforming Growth Factor-beta (TGF-β), connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on which research has been currently focusing.This review initially discusses those drugs used in clinical practice for their anti-fibrotic properties and later examines emerging pathway-specific agents in preclinical and clinical development [phase I and II-concluded or ongoing trials]. We performed a PubMed, Embase and Google Scholar research including original articles, systematic reviews, ongoing and completed trials using combinations of keywords such as 'myocardial fibrosis', 'reverse remodeling', 'RAAs', 'therapy'.A variety of preclinical evidences suggest that new drugs and molecules are potentially useful to target cardiac fibrosis and improve left ventricular function, reduce infarct size and scars, delay incident heart failure and cardiac dysfunction in animal models. However, there are very few clinical trials investigating the effect of such drugs in this setting, as well as a lack of new engineered molecules for specific targets.

Amyloidosis is a group of progressive and devastating disorders resulting from extracellular deposition of misfolded proteins into tissues. When deposition of fibrils occurs in cardiac tissues, this systemic disease can lead to a very poor prognosis. Systemic amyloidosis can be acquired [light chain (AL) amyloidosis; AA amyloidosis], or hereditary [transthyretin (ATTR) amyloidosis]. Cardiac disease in amyloidosis is usually secondary to a systemic disease. The diagnosis of cardiac involvement is often delayed and yields an adverse prognosis.in this review, the authors report current literature on advances in pharmacotherapy for cardiac amyloidosis, mainly focused on AL and ATTR amyloidosis treatment.Most pharmacological trials in amyloidosis patients, both AL and TTR, are directed to study the effects of drugs on polyneuropathy. However, since cardiac involvement carries a prominent negative survival impact in amyloidosis patients, future research should be more focused on amyloidosis cardiomyopathy as primary endpoint. Additionally, in AL amyloidosis therapies are mainly derived from experience on multiple myeloma treatment. In this specific setting, possible future research could particularly focus on immunotherapeutic agents able to optimize the standard chemotherapy results and, thus, allowing a larger population of patients to be treated by bone marrow stem cell transplantation.

Background Spindle cell oncocytomas are extremely rare neoplasms of the sellar, parasellar, and suprasellar regions that can frequently mimic pituitary adenomas. Fewer than 50 cases have been ever reported in the literature, and there is no consensus on best treatments to be provided. Case Description We hereby present a challenging case of sellar and suprasellar spindle cell oncocytoma in a patient of 64 years. The patient, who presented with hydrocephalus, hypopituitarism, and visual deficit, underwent urgent transsphenoidal (TNS) resection of the mass, which was aborted for massive life-threatening bleeding. The patient received ventriculoperitoneal shunt with relief of symptoms. An endovascular embolization of tumor feeders from the distal portion of the right internal maxillary artery, in particular the sphenopalatine artery, was then performed and a second-look TNS surgery was feasible. The patient was discharged in optimal clinical condition, recovered both endocrinologic and visual deficits, and is now in follow-up. Conclusions We found that the oncocytoma was radiologically and clinically comparable with a pituitary adenoma, except for higher representation of vasculature. According to our recent experience and review of the literature, we believe that surgery (transsphenoidal or transcranial approach) is the recommended treatment in those who are symptomatic and preoperative embolization might be a suitable option to reduce intraoperative bleeding and increase radicality.

Background Vertebral hemangioma resection can be a real challenge for spine surgeons, given the high potential of massive intraoperative bleeding. For this reason, preoperative transarterial embolization of this tumor is supported by the available literature. Here, we discuss our difficulties in interpreting an unusual clinical and radiologic picture related to the endovascular procedure. Methods and Results A 45-year-old man was referred to our department due to chronic back pain and progressive lower extremity weakness. Radiologic assessment was obtained by means of spinal computed tomography (CT) and magnetic resonance imaging (MRI), which showed an aggressive vertebral hemangioma in T7, compressing the spinal cord. The patient underwent a combined therapeutic approach consisting of preoperative transarterial embolization followed by tumor resection, spinal cord decompression, and posterior thoracic arthrodesis. The patient was dismissed with neither strength nor sensory deficits. Two weeks later, he returned to our department with fever. A new MRI demonstrated multiple areas of altered signal in almost all vertebral bodies from T6 down to the sacrum. After a deep diagnostic process, including new MRI and infectious disease evaluations, the definitive diagnosis of multiple vertebral bone infarction was suggested. Conclusion Vertebral infarctions are an extremely rare complication of spinal endovascular procedures. To our knowledge, this is the first case of multiple postembolization vertebral infarctions, without spinal cord involvement. This peculiarity was explained by the presence of direct anastomoses between a posterior intercostal artery and the underlying vertebral bodies.

Acute coronary syndromes can develop with an unusual and challenging presentation. Kounis syndrome is a mostly overlooked Acute Coronary Syndrome (ACS) in the setting of anaphylactic or anaphylactoid reactions in response to an allergic insult that can lead to severe complications including cardiac arrest. A 52-yearold- man presented to the emergency department of our hospital because of acute transient loss of consciousness that developed some minutes after almonds ingestion. The complex diagnostic workup led to the diagnosis of vasospastic Kounis syndrome, an infrequent type of acute coronary syndrome, mostly overlooked, with challenging diagnostic and therapeutic features. Peculiarities on clinical presentation, the approach adopted by the emergency physician and the consultant cardiologist to achieve the correct diagnosis and our proposed management with a brief revision of the literature will be reported. Unusual clinical presentations of acute coronary syndromes represent part of the pitfalls that an emergency physician can face during the everyday practice. Prompt identification of these conditions is always struggling but of crucial importance to improve patient prognosis with a correct diagnostic work-up and therapeutic management.

Background The year 2020 was dramatically characterized by SARS-CoV-2 pandemic outbreak. COVID-19-related heart diseases and myocarditis have been reported. Case summary A 45-year-old healthy male was admitted to the intensive care unit of our hospital because of cardiogenic shock. A diagnosis of COVID-19 infection and myocarditis was done. We present here several peculiarities about diagnostic workup, myocardial histological findings, choice of treatment, and the patient clinical course at 3 and 8 months of follow-up. Discussion COVID-19 myocardial damage and myocarditis are mainly linked to the cytokine storm with mild myocardial inflammatory infiltrate and very unusual platelet microclots in the setting of the microvascular obstructive thrombo-inflammatory syndrome. Counteracting the inflammatory burden with an interleukine-1 inhibitor appeared safe and led to a dramatic and stable improvement of cardiac function.

Background Despite advances in endoscopic transnasal transsphenoidal surgery (ETNS) for pituitary adenomas (PAs), cerebrospinal fluid (CSF) leakage remains a life-threatening complication predisposing to major morbidity and mortality. In the current study we developed a supervised ML model able to predict the risk of intraoperative CSF leakage by comparing different machine learning (ML) methods and explaining the functioning and the rationale of the best performing algorithm. Methods A retrospective cohort of 238 patients treated via E-TNS for PAs was selected. A customized pipeline of several ML models was programmed and trained; the best five models were tested on a hold-out test and the best classifier was then prospectively validated on a cohort of 35 recently treated patients. Results Intraoperative CSF leak occurred in 54 (22,6%) of 238 patients. The most important risk's predictors were: non secreting status, older age, x-, y- and z-axes diameters, ostedural invasiveness, volume, ICD and R-ratio. The random forest (RF) classifier outperformed other models, with an AUC of 0.84, high sensitivity (86%) and specificity (88%). Positive predictive value and negative predictive value were 88% and 80% respectively. F1 score was 0.84. Prospective validation confirmed outstanding performance metrics: AUC (0,81), sensitivity (83%), specificity (79%), negative predictive value (95%) and F1 score (0,75). Conclusions The RF classifier showed the best performance across all models selected. RF models might predict surgical outcomes in heterogeneous multimorbid and fragile populations outperforming classical statistical analyses and other ML models (SVM, ANN etc.), improving patient management and reducing preventable morbidity and additional costs.

Objective To assess organizational and technical difficulties of neurosurgical procedures during the coronavirus disease 2019 (COVID-19) pandemic and their possible impact on survival and functional outcome and to evaluate virological exposure risk of medical personnel. Methods Data for all urgent surgical procedures performed in the COVID-19 operating room were prospectively collected. Preoperative and postoperative variables included demographics, pathology, Karnofsky performance status (KPS) and neurological status at admission, type and duration of surgical procedures, length of stay, postoperative KPS and functional outcome comparison, and destination at discharge. We defined 5 classes of pathologies (traumatic, oncological, vascular, infection, hydrocephalus) and 4 surgical categories (burr hole, craniotomy, cerebrospinal fluid shunting, spine surgery). Postoperative SARS-CoV-2 infection was checked in all the operators. Results We identified 11 traumatic cases (44%), 4 infections (16%), 6 vascular events (24%), 2 hydrocephalus conditions (8%), and 2 oncological cases (8%). Surgical procedures included 11 burr holes (44%), 7 craniotomies (28%), 6 cerebrospinal fluid shunts (24%), and 1 spine surgery (4%). Mean patient age was 57.8 years. The most frequent clinical presentation was coma (44 cases). Mean KPS score at admission was 20 ± 10, mean surgery duration was 85 ± 63 minutes, and mean length of stay was 27 ± 12 days. Mean KPS score at discharge was 35 ± 25. Outcome comparison showed improvement in 16 patients. Four patients died. Mean follow-up was 6 ± 3 months. None of the operators developed postoperative SARS-CoV-2 infection. Conclusions Standardized protocols are mandatory to guarantee a high standard of care for emergency and urgent surgeries during the COVID-19 pandemic. Personal protective equipment affects maneuverability, dexterity, and duration of interventions without affecting survival and functional outcome.

With ageing population the number of elderly vulnerable to abuse is expected to grow. Hospital personnel play a crucial role in identifying mistreatment. The aim of this study was to establish the level of awareness and perception of elder abuse by healthcare workers, and to understand if they are able to recognize and properly report elder abuse, as well as to identify the physical signs of abuse and neglect. A 41-question survey was administered to healthcare professionals, working in the Internal Medicine and Geriatric Wards of two different University Hospitals of Southern Italy, representative of the Italian health public system. The data collection resulted in 98 questionnaires. For the majority, neglect represents a type of abuse, whereas 40% of physicians and 37% of nurses considered this concept false. All the professionals recognized the elder abuse as a violation of the human rights, but 46.94% were not sure about the existence of standard procedures for abuse reporting/treatment. The most of the nurses and the care assistants declared they never had suspected or witnessed abuse, while few physicians stated to have suspected/witnessed abuse 1-3 times in their career. In both the suspected and witnessed cases, the healthcare personnel did not made any action, neither reported them to public authorities nor adult protective service agencies. The level of awareness and perception of elder abuse by healthcare professionals are still poor especially regarding the reporting procedures. There is still strong need for education and specific training programs on elder abuse.

Object: To investigate those parameters affecting early and follow-up functional outcomes in patients undergoing resection of meningiomas and to design a dedicated predictive score, the Milan Bio(metric)-Surgical Score (MBSS) is hereby presented. Methods: Patients undergoing transcranial surgery for intracranial meningiomas were included. The most significant parameters in the regression analyses were implemented in a patient stratification score and were validated by testing its classification consistency with a clinical–radiological grading scale (CRGS), Milan complexity scale (MCS), and Charlson Comorbidity Index (CCI) scores. Results: The ASA score, Frailty index, skull base and posterior cranial fossa locations, a diameter of >25 mm, and the absence of a brain–tumour interface were predictive of early post-operative deterioration and were collected in MBSS Part A (AUC: 0.965; 95%C.I. 0.890–1.022), while the frailty index, posterior cranial fossa location, a diameter of >25 mm, a edema/tumour volume index of >2, dural sinus invasion, DWI hyperintensity, and the absence of a brain–tumour interface were predictive of a long-term unfavourable outcome and were collected in MBSS Part B (AUC: 0.877; 95%C.I. 0.811–0.942). The score was consistent with CRGS, MCS, and CCI. Conclusion: Patients’ multi-domain evaluation and the implementation of frailty indexes might help predict the perioperative complexity of cases; the functional, clinical, and neurological early outcomes; survival; and overall QoL after surgery.

Objectives Hepatocellular carcinoma (HCC) is one of the most frequent tumours worldwide and available drugs are inadequate for therapeutic results and tolerability. Hence, novel effective therapeutic tools with fewer side effects are of paramount importance. We have previously shown that Crithmum maritimum ethyl acetate extract exerts a cytostatic effect in HCC cells. Here, we tested whether C. maritimum ethyl acetate extract in combination with half sorafenib IC50 dose ameliorated efficacy and toxicity of sorafenib in inhibiting liver cancer cell growth. Moreover, we investigated the mechanisms involved. Methods Two HCC cell lines (Huh7 and HepG2) were treated with C. maritimum ethyl acetate extract and half IC50 sorafenib dose usually employed in vitro. Then, cell proliferation, growth kinetics and cell toxicity were analysed together with an investigation of the cellular mechanisms involved, focusing on cell cycle regulation and apoptosis. Key findings Results show that combined treatment with C. maritimum ethyl acetate extract and half IC50 sorafenib dose decreased cell proliferation comparably to full-dose sorafenib without increasing cell toxicity as confirmed by the effect on cell cycle regulation and apoptosis. Conclusions These results provide scientific support for the possibility of an effective integrative therapeutic approach for HCC with fewer side effects on patients.

Background The role of the target vessel in percutaneous revascularization of chronic total occlusion (CTO) is unclear. Objective We sought to assess the long-term results of percutaneous coronary intervention (PCI) for CTO lesions in each coronary artery and to investigate the impact of successful revascularization and previous myocardial infarction (MI) in the territory of the target vessel. Methods and results Cohort observational study on 1,124 patients who have undergone CTO PCI attempt: 371 on left anterior descending artery (LAD), 485 right coronary artery, and 268 left circumflex. Patients were further stratified by successfully revascularized and not-revascularized CTO (CTO-NR). Vessels affected by a previous MI were defined as infarct-related artery (IRA). The primary endpoint was cardiac death; the secondary endpoint was the combined rate of sudden cardiac-death and sustained ventricular-arrhythmias (SCD/SVAs). Propensity score-matching was performed to evaluate LAD versus NON-LAD CTO. Up to 12-year follow-up, the clinical benefit associated with successful PCI was consistent across the three groups. CTO-NR had the greatest association with cardiac death and SCD/SVAs in each coronary artery and in IRA-CTO patients. Conclusions Unsuccessful percutaneous CTO revascularization was associated with lower cardiac survival and freedom from SCD/SVAs, irrespective of the vessel treated. This result was mainly driven by patients with an IRA CTO.

Simple Summary Glioblastoma is the most common and malignant primary brain tumor, with a median survival of around 14 months. The aggressiveness of glioblastoma is due to intense cell proliferation, angiogenesis, invasiveness, genetic instability, resistance to therapies and high frequency of relapses. These features render glioblastoma almost incurable, considered an extreme therapeutic challenge. In the last few decades, it has been observed a reduced cancer incidence in diabetic patients treated with metformin, an oral hypoglycemic drug. The reported ability of metformin to arrest cancer cell growth in in vitro and in vivo experimental tumor models, have suggested the possibility to reconsider metformin as an anti-cancer add-on therapy, but further investigations about molecular mechanisms and optimal therapeutic regimens are needed. Here, we tested the efficacy of metformin against primary glioblastoma endothelial cells, responsible for tumor angiogenesis, invasiveness and resistance to therapy, reporting promising results and advancing a novel target of metformin, the "sphingolipid rheostat". Background: Glioblastoma is the most aggressive primary brain malignancy in adults, with a poor prognosis of about 14 months. Recent evidence ascribed to metformin (MET), an antihyperglycemic drug, the potential to reduce cancer incidence and progression, but the molecular mechanisms underlying these effects need to be better investigated. Methods: Here, we tested the efficacy of MET on n = 10 primary glioblastoma endothelial cells (GECs), by viability and proliferation tests, as MTT and Live/Dead assays, apoptosis tests, as annexin V assay and caspase 3/7 activity, functional tests as tube-like structure formation and migration assay and by mRNA and protein expression performed by quantitative real-time PCR analysis (qRT-PCR) and Western Blot, respectively. Results: Data resulting revealed a time- and mu-dependent ability of MET to decrease cell viability and proliferation, increasing pro-apoptotic mechanisms mediated by caspases 3/7. Also, MET impacted GEC functionality with a significant decrease of angiogenesis and invasiveness potential. Mechanistically, MET was able to interfere with sphingolipid metabolism, weakening the oncopromoter signaling promoted by sphingosine-1-phosphate (S1P) and shifting the balance toward the production of the pro-apoptotic ceramide. Conclusions: These observations ascribed to MET the potential to serve as add-on therapy against glioblastoma, suggesting a repurposing of an old, totally safe and tolerable drug for novel oncology therapeutics.

Background: Despite advances in endoscopic transnasal transsphenoidal surgery (E-TNS) for pituitary adenomas (PAs), cerebrospinal fluid (CSF) leakage remains a life-threatening complication as it predisposes to meningitis and tension pneumocephalus. The purpose of the current study is to develop an accurate supervised ML model able to predict the risk of intraoperative CSF leakage by comparing different machine learning (ML) methods. Methods: A cohort of patients consecutively treated via E-TNS for PAs was selected. Clinical, radiological and endocrinological preoperative data were reviewed and elaborated through a features selecting algorithm. A customized pipeline of several ML models was programmed and trained in parallel; the best five models were included for further analyses. Selected risk factors were then used for training and hyperparameters optimization. Results: Intraoperative CSF leak occurred in 54 (22,6%) of 238 patients. Best risk’s predictors were: non secreting status, older age, x-, y- and z-axes diameters, ICD and R ratio. The random forest (RF) classifier outperformed other models, with an AUC of 0,84, high sensitivity (87%) and specificity (82%). Positive predictive value and negative predictive value were 69% and 93% respectively. F1 score was 0,87. Conclusion: A supervised machine learning prediction model able to identify patients at higher risk of intraoperative CSF leakage was trained and internally validated. The random forest classifier showed the best performance across all models selected by the authors. RF models might predict surgical outcomes in heterogeneous multimorbid and fragile populations outperforming classical statistical analyses and other machine learning models.

Non-alcoholic fatty liver disease (NAFLD) is an emerging and threatening pathological condition, ranging from fatty liver (FL) to chronic steatohepatitis (NASH), liver cirrhosis, and eventually to hepatocellular carcinoma (HCC). Recent findings suggest that patients with NAFLD have a higher risk of cardiovascular events and thromboembolism and that this risk is independent of metabolic diseases that are frequently associated with NAFLD, such as diabetes, hyperlipidaemia, and obesity. The vascular involvement of NAFLD might be considered its systemic burden, conditioning higher mortality in patients affected by the disease. These clinical findings suggested the existence of a prothrombotic state in NAFLD, which is partially unexplored and whose underlying mechanisms are to date not completely understood. Here, we review the mechanisms involved in the pathogenesis of the prothrombotic state in NAFLD across the progression from the healthy liver through the different stages of the disease. We focused on the possible role of several metabolic features of NAFLD possibly leading to hypercoagulation other than endothelial and platelet activation, such as insulin-resistance, nitric oxide production regulation, and gut microbiota homeostasis. Also, we analysed the involvement of plasminogen activator inhibitor-1 (PAI-1) and thromboinflammation taking place in NAFLD. Finally, we described factors striking a prothrombotic imbalance in NASH cirrhosis, with a particular focus on the pathogenesis of portal vein thrombosis.

To evaluate the relationship between cytokine balance and responsiveness to interferon-alpha (IFN-alpha), we investigated the production of IFN-gamma, interleukin-10 (IL-10), IL-12 p70, and IL-12 p40 by peripheral blood mononuclear cell (PBMC) cultures from patients with chronic hepatitis C (CHC) before and after 1 year of IFN-alpha treatment. Before the therapy, responder (R) patients exhibited lower IFN-gamma release, higher IL-10 production, and higher values of the IL12 p40/p70 ratio compared with nonresponders (NR). Increased sensitivity to the effects of IL-12 and IL-10, as well as higher IL-12-dependent IFN-gamma secretion, were also found in the R subset. After IFN-alpha therapy, an increase in IFN-gamma production and a decrease in the IL-12 p40/p70 ratio were observed in R patients, whereas opposite results were obtained in the NR group. Finally, the therapy induced downregulation of IL-10 production and cell responsiveness to recombinant IL-12 in all patients. These findings imply that predominance of a T helper 2 (Th2) cytokine profile in CHC patients favors the beneficial effects of IFN-alpha, thus suggesting a therapeutic role for Th1-driven stimulation of immune response. The findings also stress the primary importance of the IL-12 p40 and p70 balance in the modulation of immune responses to hepatitis C virus (HCV).

The clinical occurrence of ectopic thyroid gland is an infrequently encountered condition, resulting from a developmental abnormality during the migration of the thyroid anlage from the floor of the primitive foregut to its final position in the neck. It can be found along the way of thyroid descent, in the midline, or laterally in the neck or even in the mediastinum or under the diaphragm. This condition is often asymptomatic, whereas symptoms could be related to ectopic thyroid size, to its relationships with surrounding organs or to diseases affecting the ectopic thyroid in the same way they involve orthotopic glands. Sometimes, a growing mass can lead to the clinical suspicion of a tumor disease. On the other hand, thyroid ectopy must be distinguished from metastasis of thyroid cancer. Scintigraphy and ultrasonography are the main diagnostic means for evaluating ectopic thyroid tissue, whereas fine needle aspiration could be useful in the presence of a nodular ectopic gland or when the coexistence of an orthotopic thyroid can arise the suspicion of a metastasis from a thyroid cancer. Surgical removal is indicated in symptomatic cases, whereas radioiodine ablation is reserved to recurrent disease. In this paper we report an emblematic case of ectopic thyroid gland and a review of the literature dealing with this condition.

Cardiac hypertrophy/remodeling manifests as a critical condition which may likely predispose to the risk of fatal heart failure and multiple organ dysfunction if not efficiently addressed, as a result of irreversible neuroendocrine, autonomic and immune system imbalances. Undeniably, the over-excitation of sympathetic and/or the breakdown of central parasympathetic tone play a significant role to be the basis of the persistent immune activation in chronic heart failure (CHF) which, to a certain extent, is primed by inflammatory reactions in the Central Nervous System. Moreover, till today, the clinical management of CHF seeks the identification of molecularly targeted drugs in comparison to those considered so far. This review focuses on the possible neuroimmune-mediated pathways involved in CHF and throws light on the current therapeutic strategies.

The occurrence of delta superinfection among viremic and nonviremic HbsAg-positive carriers with different serum patterns and levels of preS1 and preS2 antigens was investigated. PreS1 and preS2 antigens in serum, as well as their levels, were found to be independent of hepatitis B virus (HBV) replicative activity. Serological evidence of hepatitis delta virus (HDV) superinfection was found in 34 out of 233 (14.6%) HBsAg-positive carriers; all these 34 patients resulted positive for antibody to hepatitis B 'e' antigen, and 33 of them were negative for circulating HBV-DNA. Delta superinfection occurred only among HBsAg-positive carriers whose sera were reactive for both preS1 and preS2 antigens (30 out of 142; 21.1%) or at least for preS1 alone (4 out of 63; 6.3%), but not among the patients with undetectable levels of both these antigens. Serum levels of both preS1 (p < 0.005) and preS2 (p < 0.001) antigens were found to be significantly higher in delta-positive HBsAg-positive carriers than in patients with HBV infection uncomplicated by HDV. In addition to confirm previous observations that the detection of both preS antigens in HBsAg-positive sera is independent of HBV replication, these findings clearly show that HDV infection requires not only the presence of HBsAg, but also the presence of preS peptides, and seem to suggest a low susceptibility of HBsAg-positive carriers with low or undetectable synthesis and secretion of HBV surface proteins to delta superinfection.

In the present study, sera from chronic hepatitis B surface antigen (HBsAg) carriers positive for antibody to hepatitis B 'e' antigen (anti-HBe) with evolutive liver disease as correlated with anti-HBe-positive healthy carriers, were examined for antibodies to hepatitis C virus (HCV). Anti-HCV antibodies were detected in 32/124 (25.8%) anti-HBe-positive carriers with chronic liver disease and in none of the 46 healthy carriers. When anti-HCV positivity was evaluated in relationship to the degree of severity of liver disease and possible confounding factors such as hepatitis B virus replication or other potential hepatolesive factors were eliminated by using logistic regression, the odds ratio of liver cirrhosis versus chronic persistent hepatitis was 18 (95%, CI 3.5-92.5). Therefore, our results indicate that HCV may be implicated in the determinism and severity of liver damage in a significant proportion of anti-HBe-positive chronic HBsAg carriers.

A few cases of sarcoidosis are associated with progressive liver disease. We report a case of sarcoidosis with prevalent hepatic location. This case emphasizes the possibility of an organ-specific extrapulmonary presentation of sarcoidosis and in this context, outlines the fact that hepatic involvement, independent of any pulmonary and/or mediastinal lymph nodes involvement, may be more frequent than has been reported up to now.