Search

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.

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.

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.

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.

IntroductionSyndrome of inappropriate antidiuresis (SIAD) can be a complication of hypothalamus-pituitary surgery. The use of tolvaptan in this setting is not well established, hence the primary aim of this study was to assess the sodium correction rates attained with tolvaptan compared with standard treatments (fluid restriction and/or hypertonic saline). Furthermore, we compared the length of hospital stay in the two treatment groups and investigated the occurrence of overcorrection and side effects including osmotic demyelination syndrome.MethodsWe retrospectively reviewed 308 transsphenoidal surgical procedures performed between 2011 and 2019 at our hospital. We selected adult patients who developed post-operative SIAD and recorded sodium monitoring, treatment modalities and outcomes. Correction rates were adjusted based on pre-treatment sodium levels.ResultsTwenty-nine patients (9.4%) developed post-operative SIAD. Tolvaptan was administered to 14 patients (median dose 15 mg). Standard treatments were employed in 14 subjects (fluid restriction n=11, hypertonic saline n=1, fluid restriction and hypertonic saline n=2). Tolvaptan yielded higher adjusted sodium correction rates (12.0 mmolL-1/24h and 13.4 mmolL-1/48h) than standard treatments (1.8 mmolL-1/24h, p-1/48h, p=0.004, vs. tolvaptan). The correction rate exceeded 10 mmolL-1/24h or 18 mmolL-1/48h in 9/14 and 2/14 patients treated with tolvaptan, respectively, and in no patient who received standard treatments. No side effects including osmotic demyelination occurred. Tolvaptan was associated with a shorter hospital stay (11vs.15 days, p=0.01).ConclusionsTolvaptan is more effective than fluid restriction (with or without hypertonic saline) and allows for a shortened hospital stay in patients with SIAD after transsphenoidal surgery. However, its dose and duration should be carefully tailored, and close monitoring is recommended to allow prompt detection of overcorrection.

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.

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.

In the present study, intrahepatic CD8+ lymphocyte infiltrates as well as HLA class I and CD54 (ICAM-1) antigen expression at both tissue and serum levels were evaluated in 54 untreated patients with chronic hepatitis C stratified on the basis of histological diagnosis (Chronic Persistent Hepatitis/Chronic Lobular Hepatitis -CPH/CLH- and Chronic Active Hepatitis -CAH-: 22 and 32 subjects, respectively). The relationships between soluble HLA-I (sHLA-I) and ICAM-1 (sICAM-1) serum levels and their membrane-bound counterparts, CD8+ liver infiltration and serum alanine aminotransferase (ALT) were also studied. A strong HLA-I and CD54 tissue expression, associated to the presence of CD8+ cell infiltrates in necro-inflammatory areas, and elevated sHLA-I and sICAM-1 serum amounts were observed in all patients. At the same time, no difference was found at tissue level between the two groups of patients with respect to the mean scores of HLA-I and CD54 expression, while CAH subjects displayed a significantly higher CD8 periportal and lobular reactivity in comparison to the other subset. Serological assays outlined higher values of circulating HLA-I molecules in CPH/CLH patients and higher sICAM-1 levels in the CAH group. Finally, a negative correlation was found between sHLA-I and ALT in CAH subjects while, in all patients, sICAM-1 positively correlated with both CD8 tissue infiltration and ALT. Our findings confirm the occurrence of an immune activation status during chronic hepatitis C and suggest that sHLA-I molecules might play a down-modulating role on immunoresponsiveness of these patients.

Based on the observation of steatosis in the majority of liver biopsy specimens from hepatitis C virus (HCV) infected patients, it has been suggested that HCV may be pathogenetically implicated. We aimed to determine the influence of possible underlying metabolic disorders on this association.In a series of 148 consecutive patients with chronic hepatitis, with and without HCV infection, we evaluated by logistic regression analysis the association between steatosis and HCV, controlling for diabetes, obesity, hyperlipidaemia and alcohol. These are all known to be factors associated with a fatty liver, and also with the histological degree of liver disease.Antibodies to HCV were detected in 121 of 148 (81.8%) patients. Steatosis, distributed in different histological patterns, was found in 73 of 121 (60%) HCV-positive and in 14 of 27 (52%) HCV-negative patients (P = NS). Using simple logistic regression, the association Of HCV to steatosis was weak and not statistically significant (OR, 1.14; 95% CI, 0.61-3.27). The same was true for hyperlipidaemia (OR, 4.45; 95% CI, 0.52-37.9). A strong and statistically significant association was found, however, between obesity and steatosis (OR, 4.18) and between steatosis and the highest degree of histological severity (Liver cirrhosis vs chronic persistent hepatitis: OR, 12.8). Using multivariate analysis, the association between steatosis and HCV was shown to be not significant. Hyperlipidaemia, among all the independent variables tested, was shown to be co-linear with obesity.Our findings seem to suggest that HCV is irrelevant as a risk factor for a fatty liver. The results indicated that there is a 'confounding' role of obesity and hyperlipidaemia, and that the severity of liver disease is associated with steatosis and HCV.

Clinical course, morphologic changes, immunohistochemical localization of HBV-associated markers (HBsAg, HBcAg), and serum HBV-DNA production are described in 2 chronic HBsAg carriers superinfected with HAV and hepatitis non-A, non-B virus. Our data suggest that the superinfections do not cause more severe disease and do not influence the clinical course of the HBsAg chronic carriers. Our observations indicate that a careful diagnosis of hepatocytolysis is necessary in HBV chronic infection, in order to discriminate causes that are able to induce severe damage in underlying disease.

Routine use of commercially available antisera against hepatitis B core antigen (HBcAg) obtained from Escherichia coli transfected with HBV-DNA, has permitted a re-evaluation of the histochemical distribution of the antigen in liver tissue. HBcAg, classically described almost exclusively in the nucleus, was found with a very high frequency in the cytoplasm of liver cells. Our data indicate, however, that formalin fixation and paraffin embedding destroy part of HBcAg antigenicity and eliminate most of its cytoplasmic expression. HBcAg was found in 6/7 (85.7%) of HBsAg/HBeAg positive subjects, and in 2/12 (16/6%) of HBsAg/anti-HBe positive subjects; in both subgroups the cytoplasmic expression of the antigen correlated with the presence of circulating hepatitis B virus-deoxyribonucleic acid (HBV-DNA).

Serum patterns of preS gene encoded proteins during the chronic phase of hepatitis B virus infection and their relationship with hepatitis B virus deoxyribonucleic acid and hepatitis B 'e' antigen were investigated. The results indicate that the presence of preS1 and/or preS2 antigens in serum does not correlate with circulating hepatitis B virus deoxyribonucleic acid and hepatitis B 'e' antigen. It is, therefore, suggested that preS antigens cannot be regarded as specific markers of active viral replication in chronically hepatitis B virus infected patients.