Incisional hernia repair with a slowly absorbable P4HB mesh: what happens after the mesh disappears? A retrospective longitudinal clinical study.

PURPOSE: To analyze the incisional hernia recurrence rate at a long-term follow-up using a biosynthetic long-term absorbable mesh in patients with a higher risk of surgical infection in a contaminated surgical field. METHODS: This was a retrospective multicentric study. All patients undergoing incisional hernia repair between 2016 and 2018 at 6 participating university centers were included. Patients were classified according to the Ventral Hernia Working Group (VHWG). All consecutive patients who underwent abdominal wall repair using biosynthetic long-term absorbable mesh (Phasix®) in contaminated fields (grade 3 and 4 of the VHWG classification) were included. Patients were followed-up until September 2021. Preoperative, operative, and postoperative data were collected. All patients' surgical site infections (SSIs) and surgical site occurrences (SSOs) were recorded. The primary outcome of interest was the clinical incisional hernia recurrence rate. RESULTS: One hundred and eight patients were included: 77 with VHWG grade 3 (71.3%) and 31 with VHWG grade 4 (28.7%). Median time follow-up was 41 months [24; 63]. Twenty-four patients had clinical recurrence during the follow-up (22.2%). The SSI and SSO rates were 24.1% and 36.1%, respectively. On multivariate analysis, risk factors for incisional hernia recurrence were previous recurrence, mesh location, and postoperative enterocutaneous fistula. CONCLUSIONS: At the 3 year follow-up, the recurrence rate with a biosynthetic absorbable mesh (Phasix®) for incisional hernia repair in high-risk patients (VHWG grade 3 and 4) seemed to be suitable (22.2%). Most complications occurred in the first year, and SSI and SSO rates were low despite high-risk VHWG grading.

Engagement of the B cell receptor for antigen differentially affects B cell responses to Toll-like receptor-7 agonists and antagonists in BXSB mice.

Nucleic acid sensors of the Toll-like receptor (TLR) family play a well-established role in the pathogenesis of lupus. This is particularly true for a single-stranded RNA-sensing TLR-7 receptor, as lupus mice lacking TLR-7 show ameliorated disease. Cytosine-guanosine dinucleotide (CpG)-DNA-sensing TLR-9, conversely, has a complex regulatory role in systemic lupus erythematosus (SLE). Much less is known about whether signals through the B cell receptor for antigen (BCR) may affect the ability of B cells to respond to suboptimal TLR-7 agonists and antagonists. We studied this question in prediseased BXSB male and female B cells. We found that male B cells responded more vigorously to numerous TLR-7 ligands and this responsiveness was enhanced further upon co-engagement of the BCR. This synergy was seen primarily with the interleukin (IL)-6 secretion. A number of 32-mer inhibitory oligonucleotides (INH-ODNs) with a nuclease-resistant phosphorothioate backbone were capable of blocking TLR-7, but not BCR-induced B cell activation, with an inhibitory concentration (IC)(50) of approximately 100 nm. Surprisingly, while the presence of a single TGC motif at the 5' end of an ODN did not increase its inhibitory capacity, INH-ODNs containing multiple TGC motifs had greater inhibitory potency. When BCR and TLR-7 were co-engaged, INH-ODNs showed a differential effect on B cell activation. Whereas apoptosis protection and G1-M entry completely escaped suppression, IL-6 secretion remained sensitive to inhibition, although with a 10-fold lower potency. Our results suggest that while TLR-7 antagonists may be considered as lupus therapeutics, simultaneous co-engagement of the TLR-7 and BCR might favour autoreactive B cell survival. This hypothesis needs further experimental validation.

B-cell receptor for antigen modulates B-cell responses to complex TLR9 agonists and antagonists: implications for systemic lupus erythematosus.

The capacity to make secondary structures significantly affects the ability of Toll-like receptor 9 (TLR9) agonists and antagonists to either induce or block TLR9-dependent activation in B cells. However, it has a minor impact on TLR9-induced activation in interferon alpha (IFNα)-producing dendritic cells. Based on the ability of inhibitory oligodeoxynucleotides to form predictable secondary structures, we have classified TLR9-antagonists into Class R ('restricted', palindromic) and Class B ('broadly reactive', linear) oligodeoxynucleotides. In non-autoreactive B cells, Class R oligodeoxynucleotides are at least 10-fold less potent TLR9-inhibitors. We wanted to determine whether engagement of the B-cell receptor for antigen could overcome this restriction. Here we show that in non-autoreactive mouse B cells, B-cell receptor for antigen engagement increased the potency of Class R oligodeoxynucleotides for TLR9 activation at least 10-fold, making it equal in potency to linear oligodeoxynucleotides. However, this enhanced potency was selective for TLR9-induced B-cell cycling and apoptosis protection while TLR9-induced IL-6, an event that strongly depends on signaling via late endosomes, still required 10 times more Class R oligodeoxynucleotides. Thus, pathway-specific effects of Class R oligodeoxynucleotides for TLR9/B-cell receptor for antigen co-stimulated B cells may have therapeutic advantages over non-selective targeting of B cells, a strategy that may be seen as a potential therapy for human systemic lupus erythematosus.

Development of an interinstitutional resident record completion policy.

Seven hospitals in the Dayton, Ohio area collaborated in the development of generic record completion policies to assist with orientation of medical school residents. A uniform delinquent record policy was also developed, which defined the steps that would be taken if records remained incomplete. The interinstitutional policies resulted in a more cooperative atmosphere among residents, the medical school, and the hospitals, which contributed to improved quality of documentation and a decrease in the number of delinquent records by as much as 70 percent.