Objective This study was aimed to evaluate the relationship between cesarean skin incision length and wound complications. Study Design Planned secondary analysis of a multicenter double-blind randomized trial of adjunctive azithromycin versus placebo (in addition to standard cefazolin) in women >= 24 weeks undergoing cesarean delivery during labor or >= 4 hours after membrane rupture. Skin incision length (cm) was measured just prior to skin closure. The primary outcome was a composite of wound complications (wound infection, separation, seroma, hematoma, or dehiscence) up to 6 weeks of postpartum. Individual components of the composite were examined as secondary outcomes. Outcomes were compared between groups defined by the lowest (<= 25th), middle (25-75th) and highest (>75th) incision length quartiles. Logistic regression was used to adjust for potential confounding variables. Results Of the 2,013 women enrolled in the primary trial, 1,916 had recorded incision lengths and were included in this secondary analysis. The overall rate of composite wound complications was 7.8%. Median incision length was 15.0 cm (interquartile range: 14.0-16.5) with the lowest quartile defined as <= 14, middle as >14 to <= 16.5, and highest as >16.5 cm. Mean BMI, parity, use of staples, and duration of surgery differed significantly between the three incision length groups. In unadjusted analysis, the longest incision lengths were associated with an increased risk of the wound composite and wound infections (odds ratio [OR] = 2.27, 95% confidence interval [CI]: 1.43-3.60 and OR = 2.30, 95% CI: 1.27-4.15, respectively) compared with the shortest incision lengths. However, after multivariable adjustments, these associations were nullified. Additional analyses considering incision length as a continuous variable and using 10th/90th percentile cut-offs still did not suggest any associations with outcomes. Conclusion Increasing skin incision length is not independently associated with an increased risk of postoperative wound complications.

OBJECTIVE:To compare the frequency of postoperative surgical site infection (SSI) by type of skin preparation used for unscheduled cesarean in the setting of adjunctive azithromycin prophylaxis. METHODS:Secondary analysis of a multi-center randomized controlled trial of adjunctive azithromycin (500 mg intravenous) versus placebo in women who were ≥24 weeks gestation and undergoing unscheduled cesarean (i.e. during labor or ≥4 h after membrane rupture). Type of skin preparation used was identified based on the protocol at the hospital at the time of delivery: iodine-alcohol, chlorhexidine, chlorhexidine-alcohol, or the combination of chlorhexidine-alcohol and iodine. The primary outcome of this analysis was incidence of post-operative SSI, as defined by CDC criteria. Multivariable logistic regression was applied for adjustments. RESULTS:All 2013 women in the primary trial were included in this analysis. Women were grouped according to type of skin preparation received: iodine-alcohol (n = 193), chlorhexidine (n = 733), chlorhexidine-alcohol (n = 656), and chlorhexidine-alcohol and iodine combined sequentially (n = 431). The unadjusted rates of wound infection ranged from 2.9% to 5.7%. Using iodine-alcohol as the referent, the adjusted odds ratios for wound SSI were 0.71 (95% CI 0.30-1.66) for chlorhexidine, 0.97 (95% CI 0.41-2.28) for chlorhexidine-alcohol, and 0.88 (95% CI 0.36-2.20) for chlorhexidine-alcohol with iodine combination. CONCLUSION:In women undergoing unscheduled cesarean delivery in a trial of adjunctive azithromycin, the type of skin preparation used did not appear to be associated with the frequency of wound SSI.

OBJECTIVE:Determine incidence and risk factors for readmissions in early infancy.STUDY DESIGN:Secondary analysis of data from the Cesarean Section Optimal Antibiotic Prophylaxis trial. All unplanned revisits (unplanned clinic, ER visits, and hospital readmissions) and hospital readmissions (initial discharge to 3-month follow-up) were analyzed.RESULTS:295 (15.9%) of 1850 infants had revisits with risk factors being ethnicity (adjusted odds ratio (aOR): 0.6 for Hispanic), maternal postpartum antibiotics (1.89), azithromycin treatment (1.22), small for gestational age (1.68), apnea (3.82), and hospital stay after birth >90th percentile (0.49). 71 (3.8%) of 1850 infants were readmitted with risk factors being antenatal steroids (aOR 2.49), elective repeat C/section (0.72), postpartum maternal antibiotics (2.22), O2 requirement after delivery room (2.82), and suspected/proven neonatal sepsis (0.55).CONCLUSION(S):Multiple risk factors were identified, suggesting potential impact on the neonatal microbiome (maternal postpartum antibiotics) or issues related to access/cost of care (Hispanic ethnicity associated with fewer revisits).

Objective Adding azithromycin to standard antibiotic prophylaxis for unscheduled cesarean delivery has been shown to reduce postcesarean infections. Because wound infection with ureaplasmas may not be overtly purulent, we assessed the hypothesis that azithromycin-based extended-spectrum antibiotic prophylaxis also reduces wound complications that are identified as noninfectious. Study Design This is a secondary analysis of the C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) randomized controlled trial, which enrolled women with singleton pregnancies ≥24 weeks who were undergoing nonelective cesarean. Women were randomized to adjunctive azithromycin or identical placebo up to 1 hour preincision. All wound complications occurring within 6 weeks were adjudicated into infection and noninfectious wound complications (seroma, hematoma, local cellulitis, and other noninfectious wound breakdown). The primary outcome for this analysis is the composite of noninfectious wound complications. Results At a total of 14 sites, 2,013 women were randomized to adjunctive azithromycin (n = 1,019) or placebo (n = 994). Groups were similar at baseline. Although there was a lower rate of noninfectious wound complications in the azithromycin group compared with placebo (2.9 vs. 3.8%), this was not statistically significant (p = 0.22). Conclusion While adding azithromycin to usual antibiotic prophylaxis for nonelective cesarean delivery does reduce the risk of postcesarean infections, it did not significantly reduce the risk of postcesarean noninfectious wound complications.

OBJECTIVE:To evaluate the association of institutional protocols for vaginal preparation with antiseptic solution and the surgical site infection rate in women undergoing cesarean delivery during labor. METHODS:This is a secondary analysis of a multicenter randomized controlled trial of adjunctive azithromycin prophylaxis for cesarean delivery performed in laboring patients with viable pregnancies. The primary outcome for this analysis was the rate of superficial or deep surgical site infection within 6 weeks postpartum, as per Centers for Disease Control and Prevention criteria. Maternal secondary outcomes included a composite of endometritis, wound infection or other infections, postoperative maternal fever, length of hospital stay, and the rates of hospital readmission, unexpected office visits, and emergency department visits. RESULTS:A total of 523 women delivered in institutions with vaginal antisepsis policies before cesarean delivery and 1,490 delivered in institutions without such policies. There was no difference in superficial and deep surgical site infection rates between women with and without vaginal preparation (5.5% vs 4.1%; odds ratio [OR] 1.38, 95% CI 0.87-2.17), even after adjusting for possible confounders (adjusted OR 0.86, 95% CI 0.43-1.73). The lack of significant benefit was noted in all other maternal secondary outcomes. CONCLUSION:Institutional policies for vaginal preparation before cesarean delivery were not associated with lower rates of surgical site infection in women undergoing cesarean delivery during labor.

In the vestibular peripheral organs, type I and type II hair cells (HCs) transmit incoming signals via glutamatergic quantal transmission onto afferent nerve fibers. Additionally, type I HCs transmit via 'non-quantal' transmission to calyx afferent fibers, by accumulation of glutamate and potassium in the synaptic cleft. Vestibular efferent inputs originating in the brainstem contact type II HCs and vestibular afferents. Here, we aimed at characterizing the synaptic efferent inputs to type II HCs using electrical and optogenetic stimulation of efferent fibers combined with *in vitro* whole-cell patch clamp recording from type II HCs in the rodent vestibular crista. Properties of efferent synaptic currents in type II HCs were similar to those found in cochlear hair cells and mediated by activation of α9/α10 nicotinic acetylcholine receptors (AChRs) and SK potassium channels. While efferents showed a low probability of release at low frequencies of stimulation, repetitive stimulation resulted in facilitation and increased probability of release. Notably, the membrane potential of type II HCs measured during optogenetic stimulation of efferents showed a strong hyperpolarization even in response to single pulses and was further enhanced by repetitive stimulation. Such efferent-mediated inhibition of type II HCs can provide a mechanism to adjust the contribution of signals from type I and type II HCs to vestibular nerve fibers. As a result, the relative input of type I hair cells to vestibular afferents will be strengthened, emphasizing the phasic properties of the incoming signal that are transmitted via fast non-quantal transmission. ### New and Noteworthy Type II vestibular hair cells (HCs) receive inputs from efferent fibers originating in the brainstem. We used *in vitro* optogenetic and electrical stimulation of efferent fibers to study their synaptic inputs to type II HCs. Efferent inputs inhibited type II HCs, similar to cochlear efferent effects. We propose that efferent inputs adjust the contribution of signals from type I and type II HCs that report different components of the incoming signal to vestibular nerve fibers.

OBJECTIVE:To identify maternal clinical risk factors for postcesarean maternal infection in a randomized clinical trial of preincision extended-spectrum antibiotic prophylaxis.METHODS:We conducted a planned secondary analysis of a randomized clinical trial. Patients were 24 weeks of gestation or greater and delivered by cesarean after a minimum of 4 hours of ruptured membranes or labor. All participants received standard preincision prophylaxis and were randomized to receive azithromycin or placebo. The primary outcome for this analysis is maternal infection: a composite outcome of endometritis, wound infection (superficial or deep), or other infections occurring up to 6 weeks postpartum. Maternal clinical characteristics associated with maternal infection, after controlling for azithromycin assignment, were identified. These maternal factors were included in a multivariable logistic regression model for maternal infection.RESULTS:Of 2,013 patients, 1,019 were randomized to azithromycin. Overall, 177 (8.8%) had postcesarean maternal infection. In the final adjusted model, compared with the reference groups, women of black race-ethnicity, with a nontransverse uterine incision, with duration of membrane rupture greater than 6 hours, and surgery duration greater than 49 minutes, were associated higher odds of maternal infection (all with adjusted odds ratios [ORs] of approximately 2); azithromycin was associated with lower odds of maternal infection (adjusted OR 0.4, 95% confidence interval 0.3-0.6).CONCLUSION:Despite preincision azithromycin-based extended-spectrum antibiotic prophylaxis, postcesarean maternal infection remains a significant source of morbidity. Recognition of risk factors may help guide innovative prevention strategies.CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, https://clinicaltrials.gov, NCT012235546.

Standard antibiotic prophylaxis (AP) for Cesarean delivery (CD) does not cover some organisms such as Ureaplasmas, which are frequently associated with post-CD infections. We evaluated the effect of adding azithromycin (AZI) to usual AP on post-CD infections in women undergoing non-elective CD. The multicenter double-blind C/SOAP RCT (CT.gov NCT01235546), included women with singletons ≥24 wks’ GA who had CD during labor or at least 4 hrs after membrane rupture. All women received standard AP. Subjects were randomized to also receive either AZI (500mg in 250ml saline) or identical placebo (250ml saline) by a center-stratified computer-generated scheme. Study medication was given preferably up to 1 hr pre-incision (or as soon as possible after). The centrally adjudicated primary outcome was a composite of endometritis, wound infection, or other infection (abdominopelvic abscess, sepsis, pelvic septic thrombophlebitis, pyelonephritis, pneumonia or meningitis) within 6 wks. Secondary outcomes included neonatal morbidities and reported adverse events. We estimated that N=2000 would be needed to show a ≥33% reduction in the primary outcome from a baseline of 8-12% with 80% power and 2-sided alpha of 0.05. Analysis was by intent-to-treat. Of 17,790 women screened from 04/2011 to 11/2014, 2013 were randomized to AZI (n=1019) or placebo (n=994) at 14 sites. Groups were similar at baseline (35% Caucasian, 34% Black, 29% Latino and mean BMI of 29.9). Drug was administered before incision in 88% per group. The primary outcome occurred significantly less in the AZI group compared to placebo (Table; 6 vs 12%, p

BACKGROUND:The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section.METHODS:In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks.RESULTS:The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P=0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P=0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P=0.63).CONCLUSIONS:Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546 .).

Platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor Type 1 have demonstrated chemotactic and mitogenic properties in vitro that could benefit healing ligaments. These growth factors also have demonstrated in vivo effects when used in skin wound-healing models. In a previous study, bFGF and IGF-1, used alone, failed to improve healing. The authors wished to test the hypothesis that platelet-derived growth factor alone or combinations of platelet-derived growth factor plus insulin-like growth factor Type 1, platelet-derived growth factor plus basic fibroblast growth factor, or basic fibroblast growth factor plus insulin-like growth factor Type 1 would increase the healing efficiency of ligaments because of their effects on different parts of the cell replication cycle and their abilities to induce chemotaxis. Ligaments receiving platelet-derived growth factor alone were 73% +/- 55% stronger than their contralateral internal controls (p < 0.0025). Stiffness increased 94% +/- 63% over controls (p < 0.0025), and breaking energy was 101% +/- 104% > controls (p < 0.1). Ligaments treated with a combination of platelet-derived growth factor plus insulin-like growth factor Type 1 and platelet-derived growth factor plus basic fibroblast growth factor also had increases in rupture force, stiffness, and breaking energy over internal controls. Ligaments treated with a combination of basic fibroblast growth factor plus insulin-like growth factor Type 1 also appeared to have some improved healing; the results, however, did not prove to be statistically significant. Synergistic effects of growth factor combinations were not evident.