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Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods.

Since 2010, the rates of induction have risen in Australia (from 25% to 35%) and the United Kingdom (from 20% to 32%). This may be an indication that induction has become more acceptable among women and health providers. In women with unripe cervices, mechanical methods, such as balloon catheters, and pharmacological methods, such as vaginal prostaglandins, are commonly used for cervical ripening to induce labor. Yet, induction poses the risks of cesarean delivery (CD), as well as maternal and neonatal morbidity and mortality. Finding the optimal method to induce labor is important to reduce these risks. The aim of this study was to compare the safety and effectiveness of balloon catheters and vaginal prostaglandins for the induction of labor.This was a meta-analysis using individual patient data from published and unpublished randomized controlled trials that had completed data collection between March 19, 2019, and May 1, 2021. A recent Cochrane review provided additional trials completed before March 19. Eligible trials were those that compared single- or double-balloon catheters with the vaginal prostaglandins, misoprostol, or dinoprostone. The analysis included only women with viable, singleton pregnancies with no exclusion for parity or membrane status. The primary outcomes were CD, a composite of adverse maternal outcomes, and a composite of adverse perinatal outcomes.A total of 12 trials, representing 5460 deliveries, were included in the analysis. Overall, the crude incidence of CD was 27%, the perinatal composite was 13.6%, and the maternal composite was 22.7%. No significant differences in the rate of CD were found between patients who received a balloon catheter and those given vaginal prostaglandin to induce labor (12 trials, 5414 women; adjusted odds ratio [aOR], 1.09; 95% confidence interval [CI], 0.95–1.24). The adverse perinatal composite was lower among those who received balloon catheters (10 trials, 4452 neonates; aOR, 0.80 [95% CI, 0.70–0.92]; I2= 0%). There were no significant differences for the adverse maternal composite measure (10 trials, 4326 women; aOR, 1.02 [95% CI, 0.89–1.18]; I2= 0%). Balloon catheters were associated with fewer instrumental vaginal births than vaginal prostaglandins (10 trials, 4888 women; aOR, 0.82 [95% CI, 0.68–1.00]). In a subgroup analysis, there was a lower chance of the adverse perinatal composite with the use of a single-balloon catheter versus vaginal prostaglandins (9 trials, 2683 neonates; aOR, 0.84 [95% CI, 0.71–0.99]).This study found that labor induction with balloon catheters and vaginal prostaglandins was equally effective and had similar rates of CD and adverse composite maternal outcome. However, induction with a balloon catheter was observed to improve perinatal outcomes.

To determine whether successful weight loss before ovarian stimulation with intrauterine insemination (OS-IUI) affects the risk of future pregnancy complications among women with obesity and unexplained infertility after fertility treatment.

(Abstracted from N Engl J Med2022;386:1781–1792)Chronic hypertension affects >2% of pregnancies in the United States and disproportionately affects Black women. The condition is also associated with an increased risk of adverse neonatal outcomes, including preeclampsia, placental abruption, preterm birth, small for gestational age (SGA), or perinatal death, and maternal outcomes, including maternal death, heart failure, stroke, pulmonary edema, or acute kidney injury.

Proverbs 25.27, particularly the second verset (27b) as found in the Masoretic Text, has created problems for interpreters. This paper identifies those problems and then lists, summarizes, and evaluates the major options that interpreters have offered as well as offering a couple of new options based on recognizing a double entendre.

(Abstracted from N Engl J Med2022;386:1781–1792)Chronic hypertension develops in 2% of pregnancies in the United States. As this condition disproportionately affects Black women and is associated with 3 to 5 times the risk of placental abruption, preeclampsia, preterm birth (PTB), small-for-gestational-age (SGA) birthweight, and perinatal death, optimizing treatment is critical to possibly preventing these associated complications.

ObjectiveTo explore whether physical activity is inversely associated with the onset of depression, we quantified the cumulative association of customary physical activity with incident depression and with an increase in subclinical depressive symptoms over time as reported from prospective observational studies.DesignSystematic review and meta-analysis.Data sourcesMEDLINE, PsycINFO, PsycARTICLES and CINAHL Complete databases, supplemented by Google Scholar.Eligibility criteriaProspective cohort studies in adults, published prior to January 2020, reporting associations between physical activity and depression.Study appraisal and synthesisMultilevel random-effects meta-analysis was performed adjusting for study and cohort or region. Mixed-model meta-regression of putative modifiers.ResultsSearches yielded 111 reports including over 3 million adults sampled from 11 nations in five continents. Odds of incident cases of depression or an increase in subclinical depressive symptoms were reduced after exposure to physical activity (OR, 95% CI) in crude (0.69, 0.63 to 0.75; I2=93.7) and adjusted (0.79, 0.75 to 0.82; I2=87.6) analyses. Results were materially the same for incident depression and subclinical symptoms. Odds were lower after moderate or vigorous physical activity that met public health guidelines than after light physical activity. These odds were also lower when exposure to physical activity increased over time during a study period compared with the odds when physical activity was captured as a single baseline measure of exposure.ConclusionCustomary and increasing levels of moderate-to-vigorous physical activity in observational studies are inversely associated with incident depression and the onset of subclinical depressive symptoms among adults regardless of global region, gender, age or follow-up period.

Burns of the face and neck are devastating injuries with significant psychological and functional morbidity. A detailed understanding of the severity of head and neck burns is key to effective acute management of these injuries and prevention of long-term complications. This article focuses on acute management of burns of the face and skin both in the inpatient setting and managing the sequelae of facial burns including hypertrophic scarring, contractures, and functional issues such as microstomia and ectropion. [ABSTRACT FROM AUTHOR]

Maintaining body temperature is a unique challenge with burn care. We sought to describe core temperature goals in the operating room (OR) and the methods used to achieve and maintain these goals, along with current methods of warming in the intensive care unit (ICU), the perception of effect of increased ambient temperature on work performance, and concerns with contamination of sterile fields due to increased ambient temperature. A 24 question survey was disseminated to burn centers in the United States and Canada. The questions included demographics, target core and ambient temperatures, warming methods, and beliefs on ambient temperature’s effects. Of 121 burn centers, 52 questionnaires were completed (43% response rate). The majority of centers targeted a core temperature between 36 and 38°C in the OR and an ambient temperature between 75 and 95°F in the ICU. The most common methods for maintaining core temperature included warmed ambient temperature, forced air devices, and intravenous fluids. Although the majority of centers reported the belief that increased ambient temperature benefits patients, many also reported that there is a negative impact on staff performance and risk of staff perspiration contaminating sterile fields. Burn centers reported a range of target core temperatures and methods to reach target temperatures. More than a third of respondents perceived a negative impact work performance while more than half acknowledged the potential for contamination of sterile fields. A prospective observational study is needed to determine actual temperature regulation practice patterns and its impact on outcomes.

AbstractObjectives:This study examined the longitudinal associations of objectively measured physical activity, sedentary behavior, and diet quality with two measures of adiposity and a measure of weight status.Methods:A total of 658 children from 21 elementary schools (45.1% boys; 40% white, 33% black, 9% Hispanic, and 18% other race/ethnicity) were assessed at least twice in fifth, sixth, and/or seventh grade. Fat mass index (FMI), percent body fat (PBF), and BMI were calculated from body weight, standing and seated heights, and bioelectrical impedance (BIA) measured each year.Results:At follow-up, both FMI and PBF decreased among boys and increased among girls, while BMI increased in both boys and girls. After controlling for race/ethnicity, parent education, and maturity offset at baseline, growth curve analyses showed that moderate-to-vigorous physical activity (MVPA) was significantly and negatively associated with FMI, PBF, and BMI for both boys and girls. After forming tertiles of fifth grade MVPA, least-square means for FMI, PBF, and BMI were examined by grade and gender. For both boys and girls, higher MVPA was associated with lower FMI, PBF, and BMI at all three grade levels. The relationships between sedentary behavior and diet quality and FMI, PBF, and BMI were not consistent for boys or girls.Conclusions:As boys and girls transitioned from elementary to middle school, children who participated in higher levels of MVPA maintained more favorable levels of two indicators of adiposity and a measure of weight status. These findings support the need for interventions to help children meet current public health guidelines for physical activity.

Major physiologic alterations following a severe thermal injury disrupt thermal homeostasis and predispose burn patients to hypothermia. An important recommendation in many clinical practice guidelines is to increase the ambient temperature during the care of severely burned patients in the operating room and intensive care unit to mitigate the loss of thermoregulation, prevent hypothermia, and minimize the impact of hypermetabolism. However, the scientific support for this recommendation remains unclear. This review summarizes the current knowledge regarding the pathophysiology and treatment of thermal injury–induced hypermetabolism and hypothermia, with special emphasis on alterations in ambient temperature. Current evidence on the value of increasing ambient temperature during the care of severely burned patients in the operating room or intensive care unit is limited, with minimal human studies investigating physiologic benefit or potential adverse effects.

Objective: Despite advances in the use of topical and parenteral antimicrobial therapy and the practice of early tangential burn-wound excision to manage bacterial load, 60% of the mortality from burns is attributed to bacterial biofilm infection. A low electric field (~1V) generated by the novel FDA-cleared wireless electroceutical dressing (WED) was previously shown to significantly prevent and disrupt burn biofilm infection in preclinical studies. Based on this observation, the purpose of this clinical trial was to evaluate the efficacy of the WED dressing powered by a silver- zinc electro-couple in the prevention and disruption of biofilm infection. Approach: A prospective, randomized, controlled, single center clinical trial was performed to evaluate the efficacy of the WED compared to standard of care (SoC) dressing to treat biofilms. Burn wounds were randomized to receive either SoC or WED. Biopsies were collected on days 0 and 7 for histology, scanning electron microscopy (SEM) examination of biofilm and for quantitative bacteriological analyses. Results: In total, 38 subjects were enrolled in the study. In 52% of the WED treated wounds, little to no biofilm could be detected by SEM. WED significantly lowered or prevented increase of biofilm in all wounds compared to the pair matched SoC treated wounds. Innovation: WED is a simple, easy, and rapid method to protect the wound, while also inhibiting infection. It is activated by a moist environment and the electrical field induces transient and micro molar amounts of superoxide anion radicals that will prevent bacterial growth. Conclusion: WED decreased biofilm infection better when compared to SoC.

This chapter highlights the importance of a comprehensive burn scar treatment plan in approaching a burn survivor. General concepts of burn scar physiology and a practical system to describe burn scars based on etiology, biology and symptoms are presented. Common scar management modalities, including non-surgical, surgical, and adjuvant therapies are further discussed.

Significance:While the survival rate of the severely burned patient has improved significantly, relatively little progress has been made in treatment or prevention of burn-induced long-term sequelae, such as contraction and fibrosis.Recent Advances:Our knowledge of the molecular pathways involved in burn wounds has increased dramatically, and technological advances now allow large-scale genomic studies, providing a global view of wound healing processes.Critical Issues:Translating findings from a large number of in vitroand preclinical animal studies into clinical practice represents a gap in our understanding, and the failures of a number of clinical trials suggest that targeting single pathways or cytokines may not be the best approach. Significant opportunities for improvement exist.Future Directions:Study of the underlying molecular influences of burn wound healing progression will undoubtedly continue as an active research focus. Increasing our knowledge of these processes will identify additional therapeutic targets, supporting informed clinical studies that translate into clinical relevance and practice.

The ATP-binding cassette (ABC) transporter multidrug resistance protein 1 (MRP1/ABCC1) is responsible for the cellular export of a chemically diverse array of xenobiotics and endogenous compounds. Arsenic, a human carcinogen, is a high-affinity MRP1 substrate as arsenic triglutathione [As(GS)3]. In this study, marked differences in As(GS)3transport kinetics were observed between MRP1-enriched membrane vesicles prepared from human embryonic kidney 293 (HEK) (Km3.8 µM and Vmax307 pmol/mg per minute) and HeLa (Km0.32 µM and Vmax42 pmol/mg per minute) cells. Mutant MRP1 lacking N-linked glycosylation [Asn19/23/1006Gln; sugar-free (SF)-MRP1] expressed in either HEK293 or HeLa cells had low Kmand Vmaxvalues for As(GS)3, similar to HeLa wild-type (WT) MRP1. When prepared in the presence of phosphatase inhibitors, both WT- and SF-MRP1-enriched membrane vesicles had a high Kmvalue for As(GS)3(3–6 µM), regardless of the cell line. Kinetic parameters of As(GS)3for HEK-Asn19/23Gln-MRP1 were similar to those of HeLa/HEK-SF-MRP1 and HeLa-WT-MRP1, whereas those of single glycosylation mutants were like those of HEK-WT-MRP1. Mutation of 19 potential MRP1 phosphorylation sites revealed that HEK-Tyr920Phe/Ser921Ala-MRP1 transported As(GS)3like HeLa-WT-MRP1, whereas individual HEK-Tyr920Phe- and -Ser921Ala-MRP1 mutants were similar to HEK-WT-MRP1. Together, these results suggest that Asn19/Asn23 glycosylation and Tyr920/Ser921 phosphorylation are responsible for altering the kinetics of MRP1-mediated As(GS)3transport. The kinetics of As(GS)3transport by HEK-Asn19/23Gln/Tyr920Glu/Ser921Glu were similar to HEK-WT-MRP1, indicating that the phosphorylation-mimicking substitutions abrogated the influence of Asn19/23Gln glycosylation. Overall, these data suggest that cross-talk between MRP1 glycosylation and phosphorylation occurs and that phosphorylation of Tyr920 and Ser921 can switch MRP1 to a lower-affinity, higher-capacity As(GS)3transporter, allowing arsenic detoxification over a broad concentration range.

ABSTRACTImmunization with the pneumococcal proteins pneumolysin (Ply), choline binding protein A (CbpA), or pneumococcal surface protein A (PspA) elicits protective responses against invasive pneumococcal disease in animal models. In this study, we used different mouse models to test the efficacy of a variety of multivalent protein-based vaccines that comprised various combinations of full-length or peptide regions of the immunogens Ply, CbpA, or PspA: Ply toxoid with the L460D substitution (referred to herein as L460D); L460D fused with protective peptide epitopes from CbpA (YPT-L460D-NEEK [YLN]); L460D fused with the CD2 peptide containing the proline-rich region (PRR) of PspA (CD2-L460D); a combination of L460D and H70 (L460D+H70), a slightly larger PspA-derived peptide containing the PRR and the SM1 region; H70+YLN; and other combinations. Each mouse was immunized either intraperitoneally (i.p.) or subcutaneously (s.c.) with three doses (at 2-week intervals) of the various antigen combinations in alum adjuvant and then challenged in mouse models featuring different infection routes with multiple Streptococcus pneumoniaestrains. In the i.p. infection sepsis model, H70+YLN consistently provided significant protection against three different challenge strains (serotypes 1, 2, and 6A); the CD2+YLN and H70+L460D combinations also elicited significant protection. Protection against intravenous (i.v.) sepsis (type 3 and 6A challenge strains) was largely dependent on PspA-derived antigen components, and the most protection was elicited by H70 with or without L460D or YLN. In a type 4 intratracheal (i.t.) challenge model that results in progression to meningitis, antigen combinations that contained YLN elicited the strongest protection. Thus, the trivalent antigen combination of H70+YLN elicited the strongest and broadest protection in diverse pneumococcal challenge models.

The goal of burn surgical therapy is to minimize mortality and to return survivors to their preinjury state. Prompt removal of the burn eschar, early durable coverage, and late corrections of functional deformities are the basic surgical principles. The operative burden, while presumed to be substantial and significant, is neither well described nor quantified. The burn registry at the U.S. Institute of Surgical Research Burn Center was queried from March 2003 to August 2011 for all active duty burn admissions; active duty subjects were chosen to eliminate subject follow-up as a significant variable. Subject demographics including age, sex, branch of service, injury type, injury severity score, transfusion, allograft use, length of stay, mechanism of injury, and survival were tabulated as were their percentage TBSA, specific body region involvement, and nature and dates of operations performed. Univariate analysis and multiple logistic regressions were performed to determine independent factors which predict early and late operative burden. In the 8-year study period, 864 active duty patients were admitted to the burn center. Among them, 569 (66%) were operative in nature. The operations that were performed during acute hospitalization were 62%, while the remaining 38% were performed following discharge. A linear relationship exists between TBSA and the number of acute operations with an average of one acute operation required per 5% TBSA. No direct relationships however were found between TBSA and the number of reconstructive operations. Based on multiple logistic regression, battle vs nonbattle (odds ratio [OR], 0.559; 95% confidence interval [CI], 0.298–1.050; P= .0706), injury severity score (OR, 1.021; 95% CI, 1.003–1.039; P= .0222), intensive care unit length of stay (OR, 1.076; 95% CI, 1.053–1.099; P= .0001), allograft use (OR, 2.610; 95% CI, 1.472–4.628; P= .0010), and TBSA of the trunk (OR, 0.982; 95% CI, 0.965–1.000; P= .0439) (but not overall TBSA) were associated with a high acute operative burden. Battle vs nonbattle (OR, 0.546; 95% CI, 0.360–0.829; P= .0045), and TBSA of the upper extremities (OR, 1.008; 95% CI, 1.002–1.013; P= .0042) were noted to be significant variables in predicting late reconstruction operations. The operative burden of burn, not previously well characterized, consists of operations performed during as well as after the initial hospitalization. While injury severity and truncal involvement are significant determinants of acute surgical therapy, the presence of upper extremity burns is a significant determinant of reconstruction following discharge.

Objective:The contemporary treatment of a full-thickness burn consists of early eschar excision followed by immediate closure of the open wound using autologous skin. However, most animal models study burn wound healing with the persistence of the burn eschar. Our goal is to characterize a murine model of burn eschar excision to study wound closure kinetics.Approach:C57BL/6 male mice were divided into three groups: contact burn, scald burn, or unburned control. Mice were burned at 80°C for 5, 10, or 20 s. After 2 days, the eschar was excised and wound closure was documented until postexcision day 13. Biopsies were examined for structural morphology and α-smooth muscle actin. In a subsequent interval-excision experiment (80°C scald for 10 s), the burn eschar was excised after 5 or 10 days postburn to determine the effect of a prolonged inflammatory focus.Results:Histology of both contact and scald burns revealed characteristics of a full-thickness injury marked by collagen coagulation and tissue necrosis. Excision at 2 days after a 20-s burn from either scald or contact showed significant delay in wound closure. Interval excision of the eschar, 5 or 10 days postburn, also showed significant delay in wound closure. Both interval-excision groups showed prolonged inflammation and increased myofibroblasts.Innovation and Conclusions:We have described the kinetics of wound closure in a murine model of a full-thickness burn excision. Both contact and scald full-thickness burn resulted in significantly delayed wound closure. In addition, prolonged interval-excision of the eschar appeared to increase and prolong inflammation.

Septic cardiomyopathy is a severe complication among some patients who develop group A streptococcal toxic shock syndrome. Despite the importance of cardiac dysfunction in determining prognosis, very little is known about mechanisms that reduce cardiac output in association with streptococcal infection. Here, we investigated the effects of streptococcal extracellular toxins on mechanical contractility of electrically paced primary murine cardiomyocytes. Our data demonstrate that streptolysin O (SLO) is the major streptococcal toxin responsible for cardiomyocyte contractile dysfunction. Streptolysin O dose-dependently affected cardiac myocyte function in discrete stages. Exposure to SLO caused a failure of cardiac cells to respond to electrical pacing, followed by spontaneous dysregulated contractions and augmented strength of contraction. Central to these SLO-mediated effects is a marked influx of calcium into the cytosol through SLO-mediated pores in the cytoplasmic membrane. Such calcium mobilization in response to SLO correlated temporally with hypercontractility and unpaced contractions. During continued exposure to SLO, cardiomyocytes exhibited periods of reversion to normal electrical pacing suggestive of membrane lesion repair and restoration of calcium handling. Together, these observations are consistent with the clinical observation that septic cardiomyopathy is a reversible condition in patients who survive streptococcal toxic shock syndrome. These data provide strong evidence that streptococcal exotoxins, specifically SLO, can directly impact cardiac mechanical function.

Severe acute stroke patients with critical carotid stenosis or occlusion without intracranial thrombus typically do not undergo emergent carotid thromboendarterectomy (CEA) because of the risk of reperfusion-related intracranial hemorrhage. Past studies have not consistently demonstrated benefit of early operative intervention. Cerebral computed tomography (CT), cervical and cerebral CT angiography (CTA), and cerebral CT perfusion (CTP) imaging may identify a subset of acute stroke patients without intracranial thrombus who may benefit from emergent CEA. Acute stroke patients underwent unenhanced brain CT imaging to exclude pathology that would contraindicate emergent therapy. Emergent CTAs of the intracranial and extracranial vessels were utilized to identify patients who presented with stroke symptoms based on the presence of isolated extracranial carotid disease in the absence of intracranial thromboembolism. CTP was then used to assess the extent of potentially reversible cerebral ischemia (penumbral tissue). Patients with isolated extracranial carotid lesions with significant reversible ischemia in the absence of large areas of irreversible cerebral damage underwent emergent CEA to salvage ischemic penumbra. In 1 year, 3 patients presented with large acute strokes in which CTA disclosed symptomatic extracranial internal carotid artery preocclusive or occlusive lesions without intracranial thromboembolic occlusions. CTP indicated a large area of ischemic penumbra with limited permanent injury. Mean age, time to presentation, and National Institutes of Health stroke score (NIHSS) were 66 years, 4.2 hr, and 19.3. All patients underwent emergent CEA with cervical carotid thrombectomy. Average time from stroke symptom onset to revascularization was 12.5 (range 5.9–19.0) hr. There were no perioperative deaths. At day 5, the mean NIHSS decreased to 7.6 and at day 30 was 4.7. The modified Rankin scale score dropped from a poststroke, preoperative level of 5 to 2.3 by day 30. Emergent CEA should be considered in patients presenting with large acute strokes based on favorable CT, CTA, and CTP findings. Emergent clot localization and physiological assessment of brain “tissue at risk” relative to irreversible cerebral infarction using CT, CTA, and CTP is now available. Utilization of this information by an experienced stroke team of neurologists, radiologists, and surgeons may aid in the recognition of a select group of patients in which emergent CEA may drive to improved outcomes.