A pilot study of multi-modal pain management for same-day discharge after minimally invasive repair of pectus excavatum (Nuss procedure) in children.

BACKGROUND: Despite advancements in minimally invasive repair of pectus excavatum (MIRPE), Nuss procedure, postoperative pain control remains challenging. This report covers a multimodal regimen using bilateral single-shot paravertebral block (PVB) and bilateral thoracoscopic intercostal nerve (T3-T7) cryoablation, leading to significant reduction in length of stay (LOS) and high rate of same-day discharge. METHODS: This is a comparative study of pain management protocols for patients undergoing the Nuss procedure at a single center from 2016 through 2020. All patients underwent the the same surgical technique for the treatment of pectus excavatum at a single center. Patients received bilateral PVB with continuous infusion (Group 1, n = 12), bilateral PVB with infusion and right-side cryoablation (Group 2, n = 9), or bilateral single-shot PVB and bilateral cryoablation (Group 3, n = 17). The primary outcome was LOS with focus on same-day discharge, and the secondary outcome was decreased opioid usage. RESULTS: Eleven of 17 patients in Group 3 (65%) (bilateral single-shot PVB and bilateral cryoablation) were discharged the same day as surgery. The remaining Group 3 patients were discharged the following day with no complications or interventions. Compared to Group 1 (no cryoablation), Group 3 had shorter LOS (median 4.4 days vs. 0.7 days, respectively, p < 0.001) and significantly decreased median opioid use on the day of surgery (0.92 mg/kg vs. 0.47 mg/kg, p = 0.006). CONCLUSION: Findings demonstrate the feasibility of multimodal pain management for same-day discharge after the Nuss procedure. Future multisite studies are needed to investigate the superiority of this approach to established methods. LEVEL OF EVIDENCE: III.

Conformational changes in env oligomer induced by an antibody dependent on the V3 loop base.

OBJECTIVE: The HIV-1 env oligomer is structured such that conserved, neutralizing epitopes are obscured by gp120 variable loops. We have studied the ability of an IgG2 human monoclonal antibody (hmAb), F425 B4e8 (B4e8), dependent upon the base of the V3 loop, to induce conformational changes in the env oligomer. DESIGN: The effect of B4e8 antibody on the exposure of neutralizing epitopes and viral neutralization was studied in combination with other hmAb. METHODS: Epitope exposure and viral neutralization was determined using native, intact primary isolate virions. RESULTS: B4e8 antibody neutralizes infection and binds to HIV-infected cells and primary isolate virions. B4e8 and 2G12 enhanced the binding of each other to infected cells or virus and the combination resulted in synergistic neutralization. B4e8 also enhanced the binding of CD4i and CD4 binding site antibodies. CONCLUSIONS: The conserved epitopes exposed by B4e8 are similar to those exposed by the movement of the variable loops following CD4 engagement. Further studies with select antibody combinations should provide important information for the design of effective immunotherapeutic agents.

In situ hybridization and immunolabelling study of the early replication of simian immunodeficiency virus (SIVmacJ5) in vivo.

The distribution of virus-infected cells in cynomolgus macaques was determined at 4, 7, 14 and 28 days following intravenous challenge with 1000 TCID(50) of the wild-type simian immunodeficiency virus SIVmacJ5 (stock J5C). At each time-point, pairs of macaques were killed humanely and the presence of SIV was determined and quantified in blood, spleen, peripheral and mesenteric lymph nodes, thymus, lung and ileum by virus co-cultivation with C8166 cells, by quantitative DNA PCR or by in situ hybridization (ISH). At day 4 post-infection (p.i.), detection of the virus was sporadic. By day 7 p.i., however, significant SIV loads were detected in the blood and lymphoid tissues by DNA PCR and virus co-cultivation. Large numbers of cells expressing SIV RNA were detected in mesenteric lymph nodes by ISH and significantly fewer (P<0.05) in the spleen. Significant numbers of ISH-positive cells were also observed in sections of ileum. By day 14 p.i., the distribution of SIV was more even in all lymphoid tissues analysed. By day 28, most of the tissues were negative by ISH, but all remained positive by virus isolation and DNA PCR. Immunolabelling of sections of mesenteric lymph node with monoclonal antibodies specific for SIV envelope and Nef largely confirmed the observations from ISH. These results indicate that, even following intravenous challenge, a major site of the initial replication of SIV is gut-associated lymphoid tissue. Vaccines that induce protection at this site may therefore be superior, even against parenteral challenge.

Mechanisms of protection induced by attenuated simian immunodeficiency virus.

To determine whether attenuated simian immunodeficiency virus (SIV) vaccines confer protection against superinfection via secondary cellular immune responses, we searched for markers of immune activation following rechallenge. Productive infection with either attenuated SIVmacC8 or wild-type SIVmacJ5 resulted in a transient increase in T-lymphocyte CD25 and Mafa-DR expression. A pronounced increase in the frequency of FAS+ CD8+ lymphocytes was observed following SIVmacJ5 infection only. A transient increase in lymphocytes positive for intracellular IFN-gamma and IL-4 was observed following primary infection with either virus. In contrast, lymphocytes positive for intracellular IL-2 were reduced. Following SIVmacJ5 challenge of SIVmacC8-infected vaccinees, no evidence of detectable superinfection was obtained. Rechallenge of vaccinees did not alter the frequency of activated peripheral T-lymphocytes, perturb cytokine profiles, or generate an anamnestic antibody response. These data do not support the hypothesis that protection conferred by live attenuated SIV is mediated by the induction of vigorous T-cell responses upon rechallenge.