Long-term safety of anti-TNF-α in PsA patients with concomitant HCV infection: a retrospective observational multicenter study on 15 patients

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α, in addition to its pro-inflammatory role, is an essential cytokine for the host's defense, and its depletion by treatment may facilitate the risk of viral infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in PsA patients with concurrent hepatitis C virus (HCV) infection. This is a multicenter study carried out in four Italian centers specialized in the diagnosis and treatment of PsA. At baseline and after 6 (T6) and 12 months (T12) of therapy, data concerning PsA activity and liver tests were registered. A total of 15 PsA patients with concomitant HCV infection were included in the study. At baseline, 13 patients had low viral load, and liver enzyme tests were within the normal range. During the observation period, these values remained stable. On the other hand, at baseline, a high viral load with slightly increased values of AST and ALT was detected in one patient. At T6 and T12, these values decreased. The remaining patient, at baseline, had low viral load, but with slightly increased AST and ALT values that normalized during the observation period. This is the greatest sample size available in the literature on this topic. The data suggests that anti-TNF-α agents are effective and safe in PsA patients with concomitant HCV. We suggest that the use of anti-TNF-α agents, accompanied by close monitoring, could be a therapeutic option.     

Perioperative outcomes of laparoscopic and robot-assisted major hepatectomies: an Italian multi-institutional comparative study

Background

Laparoscopic major hepatectomy (LMH), although safely feasible in experienced hands and in selected patients, is a formidable challenge because of the technical demands of controlling hemorrhage, sealing bile ducts, avoiding gas embolism, and maintaining oncologic surgical principles. The enhanced surgical dexterity offered by robotic assistance could improve feasibility and/or safety of minimally invasive major hepatectomy. The aim of this study was to compare perioperative outcomes of LMH and robotic-assisted major hepatectomy (RMH).

Methods

Pooled data from four Italian hepatobiliary centers were analyzed retrospectively. Demographic data, operative, and postoperative outcomes were collected from prospectively maintained databases and compared.

Results

Between January 2009 and December 2012, 25 patients underwent LMH and 25 RMH. The two groups were comparable for all baseline characteristics including type of resection and underlying pathology. Conversion to open surgery was required in one patient in each group (4 %). No difference was noted in operative time, estimated blood, and need for allogenic blood transfusions. Intermittent pedicle occlusion was required only in LMH (32 % vs. 0; p = 0.004). Length of hospital stay, including time spent in intensive care unit, was similar between the two groups, but patients undergoing LMH showed quicker recovery of bowel activity, with shorter time to first flatus (1 vs. 3 days; p = 0.023) and earlier tolerance to oral liquid diet (1 vs. 2 days; p = 0.001). No difference was noted in complication rate, 90-day mortality, and readmission rate.

Conclusions

This retrospective multi-institution study confirms that selected patients can safely undergo minimally invasive major hepatectomy, either LMH or RMH. The fact that intermittent pedicle occlusion could be avoided in RMH suggests improved surgical ability to deal with bleeding during liver transection, but further studies are needed before any final conclusion can be drawn.     

JAK/STAT/PKCδ molecular pathways in synovial fluid T lymphocytes reflect the in vivo T helper-17 expansion in psoriatic arthritis

Looking to the sustained psoriatic arthritis (PsA) joint as a model of local human inflammation, this study was designed to assess the T lymphocyte signal transduction pathways potentially involved in this chronic immune-mediated inflammatory process, as characterized by direct ex vivo analysis of T helper (Th)-17 T effector (Teff) cell phenotypes in synovial fluid (SF) and peripheral blood (PB) of clinically active PsA patients. The reverse-phase protein arrays (RPPA) technique was employed to identify STAT3, STAT1, JAK1, JAK2, PKCδ and ERK1/2 phosphoprotein levels on total T cell lysates in SF samples of PsA patients. Frequencies of T CD4⁺IL-17A-F⁺ and T CD4⁺IL-23R⁺ Th17 cells were quantified in SF and matched PB of PsA patients by flow cytometry and compared with PB of healthy controls (HC). Increased levels of JAK1, STAT3, STAT1 and PKCδ phosphoproteins were found in SF T cells of PsA patients, compared with PB of HC. The expansion of T CD4⁺IL-17A-F⁺ cells, as well as of T CD4⁺ cells expressing IL-23Rp19 (T CD4⁺ IL-23R⁺), considered as the pathogenic phenotype of effector Th17 cells, was found to be confined to the joints of PsA patients, as the frequencies of both populations were significantly higher in SF than in matched PB, or in PB of HC. In conclusion, T lymphocyte signal transduction pathway mapping revealed an enhanced activation of JAK1/STAT3/STAT1 and PKCδ phosphoproteins that may drive the local inflammatory process, characterized by the in vivo expansion of T CD4⁺IL-17A-F⁺ and T CD4⁺IL-23R⁺ Th17 Teff cells in SF of clinically active joints of PsA patients.     

Association between nocturnal blood pressure dipping and insulin resistance in children affected by NAFLD

The aim of this study was to analyse the relationship between insulin–glucose metabolism, nocturnal blood pressure dipping and nonalcoholic fatty liver disease (NAFLD) in obese adolescents without diabetes. One hundred one consecutive children, with biopsy-proven NAFLD, were included in this study. Blood samples were drawn for the analyses of liver function tests, insulin–glucose metabolism and lipid profile appraisal. An ambulatory blood pressure measurement (ABPM) was performed. Seventy-six children (75.3 %) were systolic nondippers, and 23 of them were diastolic nondippers (30.3 %). No differences were found in the anthropometric parameters between the two groups. When compared to the systolic dippers, the systolic nondippers had higher medians of mean nocturnal blood pressure, glucose at 0, 60 and 120 min in the oral glucose tolerance test (OGTT), OGTT insulin at all time points and insulin-resistance values. No correlation of histopathological features with dipping/nondipping statuses was found. Conclusions: We found an association between a nocturnal blood pressure fall and measures of insulin levels, independent of obesity, or daytime blood pressure levels, among the obese patients with NAFLD. Although no association between nondipping profiles and NAFLD was observed in our study, further studies with a longer term follow-up are needed, to better elucidate the complex link between these particular entities.     

Bullying Victimization,Post-Traumatic Symptoms,and the Mediating Role of Alexithymia

The purpose of this study was to examine the relationship between bullying victimization, post-traumatic stress symptoms, and alexithymia. Self-report measures concerning bullying victimization, alexithymia, and post-traumatic stress symptoms were administered to 488 adolescents (52 % boys, 48 % girls) ages 16 to 17 attending high schools. Results show that the experience of being bullied is associated with post-traumatic stress symptoms. Moreover, alexithymia mediated the impact of bullying victimization on post-traumatic stress symptoms. Findings thus show that difficulties identifying and describing feelings combined with an externally oriented thinking, the core symptoms of alexithymia, can play a crucial role in linking bullying victimization with the onset of post-traumatic stress disorder among adolescents.     

Potential Role of Omega-3 Polyunsaturated Fatty Acids in Pediatric Food Allergy

Polyunsaturated fatty acids (PUFAs) are involved both in immune system regulation and inflammation. In particular, within the PUFAs category, omega-3 (ω-3) may reduce inflammation, whereas omega-6 (ω-6) PUFAs are generally considered to have a proinflammatory effect. Recent evidence highlights an imbalance in the ω-3:ω-6 ratio with an increased intake of ω-6, as a consequence of the shift towards a westernized diet. In critical age groups such as infants, toddlers and young children, as well as pregnant and lactating women or fish allergic patients, ω-3 intake may be inadequate. This review aims to discuss the potential beneficial effects of PUFAs on pediatric food allergy prevention and treatment, both at prenatal and postnatal ages. Data from preclinical studies with PUFAs supplementation show encouraging effects in suppressing allergic response. Clinical studies results are still conflicting about the best timing and dosages of supplementation and which individuals are most likely to benefit; therefore, it is still not possible to draw firm conclusions. With regard to food-allergic children, it is still debated whether PUFAs could slow disease progression or not, since consistent data are lacking. In conclusion, more data on the effects of ω-3 PUFAs supplementation alone or in combination with other nutrients are warranted, both in the general and food allergic population.