Idatidosi Splenica. Descrizione di un caso clinico e revisione della letteratura

A rare case of primary hydatid cyst of the spleen is described. The hypotheses of this possible primary localization, diagnostic techniques and the therapeutic management are discussed

Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells

Proton pump inhibitors (PPI) target tumour acidic pH and have an antineoplastic effect in melanoma. The PPI esomeprazole (ESOM) kills melanoma cells through a caspase-dependent pathway involving cytosolic acidification and alkalinization of tumour pH. In this paper, we further investigated the mechanisms of ESOM-induced cell death in melanoma. ESOM rapidly induced accumulation of reactive oxygen species (ROS) through mitochondrial dysfunctions and involvement of NADPH oxidase. The ROS scavenger N-acetyl--cysteine (NAC) and inhibition of NADPH oxidase significantly reduced ESOM-induced cell death, consistent with inhibition of cytosolic acidification. Autophagy, a cellular catabolic pathway leading to lysosomal degradation and recycling of proteins and organelles, represents a defence mechanism in cancer cells under metabolic stress. ESOM induced the early accumulation of autophagosomes, at the same time reducing the autophagic flux, as observed by WB analysis of LC3-II accumulation and by fluorescence microscopy. Moreover, ESOM treatment decreased mammalian target of rapamycin signalling, as reduced phosphorylation of p70-S6K and 4-EBP1 was observed. Inhibition of autophagy by knockdown of Atg5 and Beclin-1 expression significantly increased ESOM cytotoxicity, suggesting a protective role for autophagy in ESOM-treated cells. The data presented suggest that autophagy represents an adaptive survival mechanism to overcome drug-induced cellular stress and cytotoxicity, including alteration of pH homeostasis mediated by proton pump inhibition

Infezione sistemica da Salmonella Arizona: discussione di un raro caso chirurgico.

Salmonella arizona enteritis has been described in patients resident in the southern states of the USA and in Mexico, whereas in Europe it is rarer. The virulence of this bacillus is, however, still little known and we have few descriptions of severe systemic infections, which are all present in patients with immune system impairment. Only two cases have been reported in Italy where the infection has occurred as severe sepsis with the pathogenic agent being isolated in the blood. Here we report what is, on the basis of our knowledge, the third case in Italy of a systemic Salmonella arizona infection

Importanza di una diagnosi precoce per un corretto trattamento chirurgico della PAES (Sindrome da intrapolamento dell’arteria poplitea).

Popliteal artery entrapment syndrome (PAES) is an uncommon pathological entity, caused by segmental popliteal artery compression by the surrounding myofascial structures. Clinical symptoms may appear acutely, with temporary ischaemic attacks, or chronically, with concerned calf claudicatio intermittens and for 30% are bilateral. Diagnosis, besides being based on clinical objectivity (acute and deep pain to the struck limb, mainly during active plantar hyperextension) and history-taking (subject-age and lack of atherosclerosis), is based on ultrasonographic (eco-color Doppler of the aortic-iliac-femural-popliteal trunks, tensiometric Doppler), angio-RM, angio-CT scan and dynamic angiographic exams. Treatment, essentially, is surgical by simple freeing of the popliteal artery from surrounding myofascial structures or by autologous vein (saphenous v.) interposition grafting and patching, or bypass without vessel resection. About clinical case reported by the authors, 44-years female with left calf acute pain symptoms, cold skin by the thermo-touch, hypo-paraesthesia with fifth toe cyanosis and walking inability, surgical treatment, because of precox diagnosis, consisted of simple cut of myofibrous shoot starting from medial head of the left gastrocnemious muscle and compressing popliteal artery, with clinical chart complete resolution

[Early laparoscopic cholecystectomy in the treatment of acute cholecystitis].

BACKGROUND: The aim of the study was to demonstrate the importance of early laparoscopic cholecystectomy for acute cholecystitis. METHODS: From 1998 to 2000, 66 patients were submitted to laparoscopic cholecystectomy. All patients were submitted to US scans preoperatively and operated on by surgeon skilled in emergency laparoscopic operative technique. RESULTS: Only one patient (1.5%) had conversion to open cholecystectomy. There was no mortality and no bile duct or major vascular injuries. The overall operative morbidity rate was 3%. The mean postoperative hospital stay was 3.1 days. CONCLUSIONS: Author's experience and results support the validity of early laparoscopic cholecystectomy in the treatment of acute cholecystitis, since it reduces the postoperative length of hospital stay and hospital costs. Early treatment is always helpful for inflamed and oedematous tissue which favours dissection

La colecistectomia laparoscopica a “bassa pressione” nei pazienti ad alto rischio (ASA III e IV) nella nostra esperienza

The insufflation pressure used for laparoscopic cholecystectomy is usually 12-15 mm Hg, and a pneumoperitoneum with carbon dioxide has a significant effect on both cardiovascular and respiratory function. These effects are transient in young, healthy patients, but may be dangerous in ASA III and IV patients with a poor cardiac reserve. This study was designed to assess the feasibility of performing laparoscopic cholecystectomy at 6.5-8 mm Hg insufflation pressure in "high-risk" patients. Thirteen patients, 10 ASA III and 3 ASA IV, with cholelithiasis, were included in this study The insufflation pressure was 6.5-8 mm Hg, with a 10 degrees anti-Trendelenburg position. The cardiovascular and blood gas variables studied were: mean arterial blood pressure, heart rate, respiratory rate, and end-tidal CO2 pressure. The authors reported no conversions and no intra- or postoperative complications. During insufflation heart rate and mean arterial blood pressure increased minimally if compared with laparoscopic cholecystectomy at 12-15 mm Hg. Pa CO2 increased after insufflation (+5 mm Hg), and the end-tidal CO2 pressure gradient was moderate (3.5 mm Hg) and unchanged during surgery. A low-pressure pneumoperitoneum is feasible for laparoscopic cholecystectomy and minimizes the adverse haemodynamic effects of peritoneal insufflation

Safety of mRNA COVID-19 Vaccines in Patients with Inborn Errors of Immunity: an Italian Multicentric Study

Purpose: Little is known about vaccine safety in inborn errors of immunity (IEI) patients during the current vaccination campaign for COVID-19. To better investigate the reactogenicity and adverse event profile after two, three, and four doses of mRNA vaccines, we conducted an observational, multicentric study on 342 PID patients from four Italian Referral Centres. Methods: We conducted a survey on self-reported adverse reactions in IEI patients who received mRNA vaccine by administering a questionnaire after each dose. Results: Over the whole study period, none of the patients needed hospitalization or had hypersensitivity reactions, including anaphylaxis and delayed injection site reaction. After two vaccination doses, 35.4% of patients showed only local reactogenicity-related symptoms (RrS), 44.4% reported both systemic and local RrS, and 5% reported only systemic RrS. In more than 60% of cases, local or systemic RrS were mild. After the first and second booster doses, patients showed fewer adverse events (AEs) than after the first vaccination course. Patients aged 50 years and older reported adverse events and RrS less frequently. Among AEs requiring treatment, one common variable immune deficiency patient affected by T cell large granular lymphocytic leukemia developed neutropenia and one patient had Bell’s paralysis perhaps during herpes zoster reactivation. Conclusion: Although our follow-up period is relatively short, the safety data we reported are reassuring. This data would help to contrast the vaccine hesitancy often manifested by patients with IEI and to better inform their healthcare providers

CD27− B-Cells Produce Class Switched and Somatically Hyper-Mutated Antibodies during Chronic HIV-1 Infection

Class switch recombination and somatic hypermutation occur in mature B-cells in response to antigen stimulation. These processes are crucial for the generation of functional antibodies. During HIV-1 infection, loss of memory B-cells, together with an altered differentiation of naïve B-cells result in production of low quality antibodies, which may be due to impaired immunoglobulin affinity maturation. In the current study, we evaluated the effect of HIV-1 infection on class switch recombination and somatic hypermutation by studying the expression of activation-induced cytidine deaminase (AID) in peripheral B-cells from a cohort of chronically HIV-1 infected patients as compared to a group of healthy controls. In parallel, we also characterized the phenotype of B-cells and their ability to produce immunoglobulins in vitro. Cells from HIV-1 infected patients showed higher baseline levels of AID expression and increased IgA production measured ex-vivo and upon CD40 and TLR9 stimulation in vitro. Moreover, the percentage of CD27−IgA+ and CD27−IgG+ B-cells in blood was significantly increased in HIV-1 infected patients as compared to controls. Interestingly, our results showed a significantly increased number of somatic hypermutations in the VH genes in CD27− cells from patients. Taken together, these results show that during HIV-1 infection, CD27− B-cells can also produce class switched and somatically hypermutated antibodies. Our data add important information for the understanding of the mechanisms underlying the loss of specific antibody production observed during HIV-1 infection