Persistent neuropathic pain after inguinal herniorrhaphy depending on the procedure (open mesh v. laparoscopy): a propensity-matched analysis

Background

A greater incidence of persistent pain after inguinal herniorrhaphy is suspected with the open mesh procedure than with laparoscopy (transabdominal preperitoneal), but the involvement of neuropathy needs to be clarified.

Methods

We examined the cumulative incidence of neuropathic persistent pain, defined as self-report of pain at the surgical site with neuropathic aspects, within 6 months after surgery in 2 prospective subcohorts of a multicentre study. We compared open mesh with laparoscopy using different analysis, including a propensity-matched analysis with the propensity score built from a multivariable analysis using a generalized linear model.

Results

Considering the full patient sample (242 open mesh v. 126 laparoscopy), the raw odds ratio for neuropathic persistent pain after inguinal herniorrhaphy was 4.3. It reached 6.8 with the propensity-matched analysis conducted on pooled subgroups of 194 patients undergoing open mesh and 125 undergoing laparoscopy (95% confidence interval 1.5–30.4, p = 0.012). A risk factor analysis of these pooled subgroups revealed that history of peripheral neuropathy was an independent risk factor for persistent neuropathic pain, while older age was protective.

Conclusion

We found a greater risk of persistent pain with open mesh than with laparoscopy that may be explained by direct or indirect lesion of nerve terminations. Strategies to identify and preserve nerve terminations with the open mesh procedure are needed.     

Addressing Early Retention in Antenatal Care Among HIV-Positive Women Through a Simple Intervention in Kinshasa,DRC: The <Emphasis Type="Italic">Elombe “Champion” Standard Operating Procedure</Emphasis>

This cluster-randomized study aimed to assess the Elombe (“Champion”) standard operating procedure (SOP), implemented by providers and Mentor Mothers, on HIV-positive pregnant women’s retention between first and second antenatal visits. Sixteen facilities in Kinshasa were randomly assigned to intervention (SOP) or comparison (no SOP). Effect of the SOP was estimated using relative risk. Women in comparison facilities were more likely to miss second visits (RR 2.5, 95% CI 1.05–5.98) than women in intervention facilities (30.0%, n = 27 vs. 12.0%, n = 9, p < 0.002). Findings demonstrate that a simple intervention can reduce critical early loss to care in PMTCT programs providing universal, lifelong treatment.     

Endoglin-mediated vascular remodeling: mechanisms underlying hereditary hemorrhagic telangiectasia

Endoglin is emerging as a pivotal component of the gateway for signaling by transforming growth factor-beta (TGF-beta) in vascular endothelial cells. Mutations in endoglin cause a rare vascular disorder in humans known as hereditary hemorrhagic telengiectasia (HHT). Although rare, in-depth analysis of mutant mice and mononuclear cells from the blood of patients with HHT have provided novel and exciting insights into how the vasculature is formed, maintained, and repaired during disease. Here, we review recent data on how endoglin is thought to function in endothelial cells and place it in the broader context of signaling by TGF-beta family members in vascular cells in general. We highlight where the controversies on underlying molecular mechanisms currently lie and indicate areas of present research focus.     

Combining brentuximab vedotin with dexamethasone,high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study

Achieving a metabolic complete response (mCR) before high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplant (auto-PBSCT) predicts progression-free survival (PFS) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL). We added brentuximab vedotin (BV) to DHAP (dexamethasone, high-dose cytarabine, cisplatin) to improve the mCR rate. In a phase I dose-escalation part of the study in 12 patients, we showed that BV-DHAP is feasible. This phase II study included 55 R/R cHL patients (23 primary refractory). Treatment consisted of three 21-day cycles of BV 1.8 mg/kg on day 1, and DHAP (dexamethasone 40 mg days 1-4, cisplatin 100 mg/m² day 1 and cytarabine 2x2 g/m² day 2). Patients with a metabolic partial response (mPR) or mCR proceeded to HDC/auto-PBSCT. Based on independent central [¹⁸F]fluorodeoxyglucose (FDG) - positron emission tomography (PET) - computed tomography (CT) scan review, 42 of 52 evaluable patients (81% [95%CI: 67-90]) achieved an mCR before HDC/auto-PBSCT, five had an mPR and five had progressive disease (3 were not evaluable). After HDC/auto-PBSCT, four patients with an mPR converted to an mCR. Two-year PFS was 74% [95%CI: 63-86] and overall survival 95% [95%CI: 90-100]. Toxicity was manageable and mainly consisted of grade 3/4 hematologic toxicity, fever, nephrotoxicity, ototoxicity (grade 1/2), and transiently elevated liver enzymes during BV-DHAP. Eighteen patients developed new onset peripheral neuropathy (maximum grade 1/2); all recovered. In conclusion, BV-DHAP is a very effective salvage regimen in R/R cHL patients, but patients should be monitored closely for toxicity. (clinicaltrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT02280993","term_id":"NCT02280993"}}NCT02280993).     

Transforming growth factor beta 1 inhibits gonadotropin action in cultured porcine Sertoli cells.

In the present study, we have tested the effects of transforming growth factor beta 1 (TGF beta 1) on FSH action toward aromatase activity and lactate production in cultured Sertoli cells isolated from immature porcine testes. Whereas treatment of Sertoli cells with FSH resulted in a dose-dependent increase (about 7-fold) in aromatase activity (conversion of testosterone into estradiol) (ED50 = 80 ng/ml FSH), the addition of TGF beta 1 reduced this gonadotropin action. The inhibitory effect of TGF beta 1 on FSH aromatase activity was dose dependent (ED50 = 0.1 ng/ml, 4 pM TGF beta 1) with a maximal decrease (about 40%) observed after a long term (48-h) treatment. TGF beta 1 exerted its inhibitory effect on FSH action at the level(s) of cAMP accumulation, exerting no apparent effect on the gonadotropin receptor or at a site(s) related to cAMP action. TGF beta 1 (2 ng/ml) significantly (P less than 0.002) reduced (52% decrease) FSH-stimulated cAMP levels in cultured porcine Sertoli cells. However, such an inhibitory effect of the growth factor was no longer observed when stimulation of cAMP accumulation with FSH occurred in the presence of methyl isobutyl xanthine (0.5 mM), an inhibitor of cAMP-phosphodiesterase activity. This observation suggests that TGF beta 1 decreased cAMP levels by increasing catabolism of the cyclic nucleotide through an enhancement of cAMP-phosphodiesterase activity. The inhibitory effect of TGF beta 1 was not limited to the action of FSH on aromatase activity but also extended to the gonadotropin action (mediated by cAMP) on lactate production. As for the inhibitory effect of TGF beta 1 on FSH-induced aromatase activity, the inhibitory effect of the growth factor on FSH-stimulated lactate production was dose and time dependent with a maximal decrease (about 30%) observed in the picomolar range (1 ng/ml, 40 pM) after 48 h treatment with TGF beta 1. In conclusion, the present study demonstrates that TGF beta 1 attenuates FSH action on Sertoli cell activity and that such inhibitory action is potentially exerted through a decrease in cAMP levels. Because of the local production of TGF beta 1, it is suggested that the effects of the growth factor reported here might be exerted in the context of the testicular paracrine mechanisms.