Antibiotic Prophylaxis against Surgical Site Infection after Open Hernia Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: The role of antibiotic prophylaxis (AP) in the prevention of surgical site infection (SSI) after hernia repair is debated. We conducted this systematic review and meta-analysis to assess the evidence on the value of prophylactic antibiotics in reducing the risks of SSI after open hernia surgery. METHODS: We ran an online and manual search to identify relevant randomized controlled trials that compared prophylactic antibiotics to nonantibiotic controls in patients undergoing open surgical hernia repair. Data on SSI risk were extracted and pooled as risk ratios (RRs) with 95% confidence intervals (95% CIs), using RevMan software. We further used the Cochrane risk of bias tool and GRADE assessment to evaluate the quality of generated evidence. RESULTS: Twenty-nine studies (N = 8,616 patients) were included in the current analysis. Antibiotic prophylaxis reduced the risk of SSI in open hernia repair patients (RR = 0.65, 95% CI = 0.53, 0.79). Subgroup analysis showed a significant benefit for antibiotics in mesh repair patients (RR = 0.60, 95% CI = 0.48, 0.76) yet no significant difference in SSI risk after herniorrhaphy (RR = 0.86, 95% CI = 0.54, 1.36). In addition, AP was associated with a significant reduction in superficial SSI risk (RR = 0.56, 95% CI = 0.43, 0.72) but not deep SSI (RR = 0.70, 95% CI = 0.30, 1.62). Further analysis showed a significant reduction in SSI risk with amoxicillin/clavulanic acid and cefazolin but not with cefuroxime. CONCLUSION: The present meta-analysis suggests that AP is beneficial prior to open mesh hernia repair. However, the quality of evidence was low, and further well-designed trials are needed.

Human regulatory T cells undergo self-inflicted damage via granzyme pathways upon activation.

Tregs hold great promise as a cellular therapy for multiple immunologically mediated diseases, given their ability to control immune responses. The success of such strategies depends on the expansion of healthy, suppressive Tregs ex vivo and in vivo following the transfer. In clinical studies, levels of transferred Tregs decline sharply in the blood within a few days of the transfer. Tregs have a high rate of apoptosis. Here, we describe a new mechanism of Treg self-inflicted damage. We show that granzymes A and -B (GrA and GrB), which are highly upregulated in human Tregs upon stimulation, leak out of cytotoxic granules to induce cleavage of cytoplasmic and nuclear substrates, precipitating apoptosis in target cells. GrA and GrB substrates were protected from cleavage by inhibiting granzyme activity in vitro. Additionally, we show - by using cytometry by time of flight (CYTOF) - an increase in GrB-expressing Tregs in the peripheral blood and renal allografts of transplant recipients undergoing rejection. These GrB-expressing Tregs showed an activated phenotype but were significantly more apoptotic than non-GrB expressing Tregs. This potentially novel finding improves our understanding of Treg survival and suggests that manipulating Gr expression or activity might be useful for designing more effective Treg therapies.

Steroid withdrawal in kidney allograft recipients.

This review highlights the aggregate of knowledge obtained from the temporal trend of kidney transplant immune suppression. We will discuss the burden of steroid side effects and their impact on quality of life in kidney allograft recipients, which have led to minimizing steroid exposure. Issues arising since the inception of the concept of steroid withdrawal will be discussed, along with how they have continually led to a shift in research focus on this subject matter. The usefulness of surveillance biopsies and how further elucidation of the pathophysiology of interstitial fibrosis and tubular atrophy could contribute to improving long-term allograft outcomes will also be discussed. We will elaborate on the role of calcineurin inhibitor minimization alongside steroid withdrawal in improving long-term graft survival. Future expectations of subsequent studies with a view to improving overall kidney allograft outcomes by eliminating attendant problems associated with steroids will also be covered.