Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects

Repair of Parastomal Hernias with Biologic Grafts: A Systematic Review

Contains fulltext : 98303.pdf (publisher's version ) (Open Access)BACKGROUND: Biologic grafts are increasingly used instead of synthetic mesh for parastomal hernia repair due to concerns of synthetic mesh-related complications. This systematic review was designed to evaluate the use of these collagen-based scaffolds for the repair of parastomal hernias. METHODS: Studies were retrieved after searching the electronic databases MEDLINE, EMBASE and Cochrane CENTRAL. The search terms 'paracolostomy', 'paraileostomy', 'parastomal', 'colostomy', 'ileostomy', 'hernia', 'defect', 'closure', 'repair' and 'reconstruction' were used. Selection of studies and assessment of methodological quality were performed with a modified MINORS index. All reports on repair of parastomal hernias using a collagen-based biologic scaffold to reinforce or bridge the defect were included. Outcomes were recurrence rate, mortality and morbidity. RESULTS: Four retrospective studies with a combined enrolment of 57 patients were included. Recurrence occurred in 15.7% (95% confidence interval [CI] 7.8-25.9) of patients and wound-related complications in 26.2% (95% CI 14.7-39.5). No mortality or graft infections were reported. CONCLUSIONS: The use of reinforcing or bridging biologic grafts during parastomal hernia repair results in acceptable rates of recurrence and complications. However, given the similar rates of recurrence and complications achieved using synthetic mesh in this scenario, the evidence does not support use of biologic grafts

Clinical, Diagnostic and Therapeutic Aspects of Implantable Cardiac Electronic Device Infections. A Five-Year Retrospective Analysis and Comparison with Literature.

Background: Infections related to implantable cardiac electronic devices (IICEDs) are increasing in incidence. Aim of our study was to evaluate: epidemiological characteristics, risk factors and type of device in patients who developed ICEDs compared to the control group; b. microbial causes and resistances; c. main signs and symptoms, laboratory and instrumental investigations; d. treatment and prognosis. Material and Methods: the study was conducted with a retrospective method, analysing all cases of IICEDs registered in our ward from April 2009 to May 2014. For each patient, were evaluated epidemiological and clinical characteristics, risk factors, diagnostic procedures, aetiology and antibiotic assays, treatment and outcome. Results: In the investigated period, 22 cases of IICEDs were registered. Demographic factors didn’t affect the risk of ICEDs. Hypertension, usually considered a risk factor, resulted to be a protective factor (p=0.0329). Age younger than 65 years, female gender, altered BMI, diabetes, dyslipidemia and smoking appear to increase the risk of IICEDs, although not significantly. The oral anticoagulant therapy was found to be a predictive negative factor (p=0.0012) as well as the type of implanted device, with particular regard to intracardiac defibrillator and biventricular devices. CoNS were isolated in 68% of cases, Staphylococcus aureus in 25% and Enterococcus faecalis in 3.5%. A polimicrobial aetiology was registered in one case (3.5%). Among the CoNS, S. epidermidis was the most represented (28.55%), followed by S. hominis (14.3%) and S. haemoliticus (14.7%). The antibiotic assays showed a high proportion of methicillin resistance (34.8%) mainly related to S. epidermidis (71.4%) followed by S. aureus (14.3%). Rifampicin was found to be resistant in 8 cases (100%) by susceptibility testing. The treatment of ICEDs showed an important heterogeneity and a very long time waiting (12.22 months) between the diagnosis and the removal of the device. Of the 22 treated patients 7 died; 3 of them were older than 90 years while 4 were aged between 61 to 68 years. Conclusion: young age, smoking and altered BMI are factors associated to the development of IICEDs, even if not statistically significant. Hypertension resulted a statistically protective factor. The suspension of oral anticoagulation therapy and assumption of perioperative heparin was found to be statistically associated with the risk of IICEDs development, because it increases the risk of hematoma formation. According to literature data, the majority of the isolated microorganisms were Staphylococci (68% CoNS and 25% S. aureus) with high rates of methicillin (34.8%) and rifampicin (100%) resistance. The difference between systemic infections and infections localized to the generator pocket is not easily distinguishable, confirming the therapeutic need of the device removal in case of infection

HIV Associated PML: an immune-mediated deregulationa disease?

ABSTRAC

Epidemiological Features of Extrapulmonary Tuberculosis in a Low-Tuberculosis Burden and High-Immigrant Reveiving City of Northern Italy

Background: Extrapulmonary tuberculosis (EPTB) contributes to the TB burden in Europe and its rate is not decreasing. Moreover, the reasons of reactivation of TB out of the lungs are not known. We conducted a study to describe the epidemiological features of EPTB in Ferrara, Italy. Methods: We retrospectively identified all the adult TB cases admitted to the Hospital of Ferrara from January 1, 2009 through December 31, 2015. TB cases were included only once and were microbiologically, histologically or clinically diagnosed. We recorded age, gender, immigrant or native status, country of birth, site of disease, diabetes, HIV status, neoplasms, CVH (chronic viral hepatitis), CLD (chronic lung disease), and year of diagnosis. Cases with simultaneous pulmonary and extrapulmonary involvement were recorded as pulmonary TB (PTB) cases. Pearson's Chi Square Test and T-test were performed for statistical analysis. Results: We identified 217 (101 women and 116 men) adult TB patients, 132 immigrants and 85 natives, 147 PTB and 70 EPTB cases. The characteristics of the immigrant and native cases at baseline were similar for mean age (36.9 among immigrants vs 66.6 among natives) and the presence of neoplastic diseases and diabetes (p<0.01). Among immigrants, 24.2% (32/132) were from Pakistan, 23.4% (31/132) from Romania, 17.4% (23/132) from Morocco. Of all 217 cases, 10 cases, 5 natives (3 PTB, 2 EPTB) and 5 immigrants (2 PTB, 3 EPTB), were HIV positive. More than half of EPTB cases (68.6%) occurred among immigrants. Considering gender, EPTB was found mostly among women (41/70), especially immigrant women (27/70 EPTB cases) (p<0.05). Regarding country of origin, Romanians developed mostly PTB (27/84 immigrant PTB cases), Pakistani EPTB (19/48 EPTB cases) (p<0.05). EPTB involved nodes in 34 cases (48.6% of all EPTB), gastrointestinal and genitourinary tract in 10 and 3, bones in 9, pleura in 6, while meninges and other sites in 2 and 6 respectively. Compared to all TB cases, nodal TB occurred mostly among women (22/34 nodal TB cases), immigrants (28/34), and Pakistani subjects (15/34, of whom 12 women), (p<0.05). Figure 1 illustrates PTB and EPTB cases by year, immigrant or native status and site of disease. Conclusions: More than half of EPTB cases occurred among immigrants. Among those subjects, gender (women) and country of origin (Pakistan) associated with EPTB and nodal TB. Nodal TB was the most common site of EPTB and was found mostly among immigrants. HIV status did not associated with EPTB. No decreasing trend in EPTB was found among immigrant or among native cases. Figure

Omental reinforcement for intraoperative leak repairs during laparoscopic Roux-en-Y gastric bypass

Leaks from the gastrojejunostomy after laparoscopic Roux-en-Y gastric bypass (LRYGB) have the potential for significant morbidity and mortality. When intraoperative leaks are discovered, we choose to perform omental reinforcement around the gastrojejunostomy and pouch after suture repair of the leaks. This study examined the hypothesis that omental reinforcement would be useful after intraoperative leaks during LRYGB. Omental reinforcement was performed on gastrojejunostomies, in which leaks were seen, created using a circular stapler during LRYGB. Data were reviewed retrospectively on these patients. There were a total of 387 patients with 32 (8.26%) patients who had a staple line dehiscence or evidence of gastric pouch or gastrojejunostomy leak intraoperatively. Leaks/dehiscences were repaired with sutures and then reinforced with omentum. None of these patient developed anastomotic leak postoperatively. Of the other 365 patients, there were four (1.1%) leaks from the gastrojejunostomy and/or gastric pouch. Omental reinforcement may be useful in decreasing the incidence of postoperative leaks when an intraoperative leak is encountered during LRYGB. However, omental reinforcement does not completely prevent a postoperative leak. Consideration of reinforcement with omentum may be given for patients in whom an intraoperative leak is noted

FATTORI PREDITTIVI DI POOR CLINICAL OUTCOMEIN CORSO DI ENCEFALITE ERPETICA

L’ encefalite erpetica rappresenta ancora oggi una patologia ad elevato rischio di sequele invalidanti, nonostante la possibilità di precoce diagnosi ed inizio immediato di terapia specifica con acyclovir. Appare necessario identificare ulteriori fattori predittivi di sequele e/o recidiv