Comparative analysis of ultrasonographic fetal lung texture in twin and singleton fetuses.

OBJECTIVES: Increased fetal lung heterogeneity has been associated with term fetal lungs in singleton gestations. The objective of this study was to determine if fetal lung heterogeneity index (HI) differs between twin and singleton fetuses in the late second and third trimesters. METHODS: Prospective cohort study of women with singleton and twin gestations with medically-indicated ultrasound examinations at 24 weeks of gestation onward. Grayscale transverse fetal lung images were obtained at the level of the four-chamber heart. A region of interest was selected in each fetal lung image. Fetal lung HI was determined with MATLAB software using a dithering technique with ultrasound image pixels transformed into a binary map form from which a dynamic range value was determined. HI averages and standard deviations were generated for twin and singleton fetuses from 24 weeks gestation onward. Two sample t-tests were used to compare the mean HI at each gestational week between singleton and twin fetuses. RESULTS: In total, 388 singleton and 478 twin images were analyzed. From 35 through 38 weeks of gestation a statistically significant divergence in mean HI was observed with higher means in singleton compared to twin fetuses. At 24 weeks of gestation there was a significantly higher HI in twin fetuses compared to singletons. No differences in fetal lung HI were observed between 25 and 34 weeks gestational age. CONCLUSIONS: Differences in fetal lung HI were observed when comparing twin and singleton fetuses. Further investigation is required to determine the potential clinical significance of these findings.

Presence and Size of Placental Lakes on 20-Week Fetal Anatomy Ultrasound and Obstetrical Outcomes.

Our objective was to determine if placental lake presence or size is associated with adverse pregnancy outcomes. This was a retrospective cohort of patients who had fetal anatomy ultrasounds at 18-22 weeks and delivered between 2018 and 2022. Placental lakes were classified as small (>2.0 to 3.9 cm) or large (≥4 cm). Multiple gestations, placenta previas, and placenta accretas were excluded. Outcomes included low birthweight, cesarean delivery, primary cesarean for non-reassuring fetal heart tracing, fetal growth restriction, preterm birth, and severe preeclampsia. A total of 1052 patients were included; 294 had placental lakes (204 small, 90 large). No differences in pregnancy outcomes were observed.

Novel characterization of CASK variant c.1963 A>G (p.Asn655Asp) through whole-exome sequencing in a monochorionic diamniotic twin fetus with significant brain anomalies: A case report.

Whole-exome sequencing is an evolving technology in perinatal diagnosis which allows identification of genetic etiologies that would otherwise go undetermined. In this case report, a 38-year-old Hispanic woman, G5P3013, with a monochorionic diamniotic twin gestation with one fetus displaying significant cranial abnormalities on prenatal ultrasound and magnetic resonance imaging (MRI) of the brain is presented. Fetal anomalies included bilateral ventriculomegaly, absent cavum septum pellucidum, and absent corpus callosum. Diagnostic amniocentesis with chromosome analysis, chromosomal microarray, alpha-fetoprotein, cytomegalovirus, toxoplasmosis, and parvovirus had normal results. Whole-exome sequencing for the anomalous fetus detected a de novo mosaic variant of uncertain significance (VUS) in the calcium/calmodulin dependent serine protein kinase (CASK) gene: c.1963 A > G (p.Asn655Asp). This variant was absent in the normal twin fetus, the mother, and the father. Pathogenic CASK gene mutations are associated with three syndromes: FG syndrome 4, intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH), and intellectual developmental disorder with or without nystagmus. Whole-exome sequencing identified a potential etiology for the anomalies detected. The variant likely arose de novo and was the potential cause of the identified cranial abnormalities in one fetus of this monochorionic diamniotic twin gestation. Whole-exome sequencing may provide additional diagnostic utility when standard diagnostic testing is noncontributory.

A Systematic Review and Clinical Presentation of Central Nervous System Complications of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Pediatric Patients During the Coronavirus Disease 2019 Pandemic in Israel.

BACKGROUND: Coronavirus disease-associated central nervous system complications (CNS-C) in hospitalized children, especially during the Omicron wave, and in comparison with influenza associated CNS-C, are not well understood. METHODS: The study population included 755 children aged <18 years hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Sheba Medical Center, during March 2020 to July 2022. A comparative cohort consisted of 314 pediatric patients with influenza during the 2018-2019 and 2019-2020 influenza seasons. RESULTS: Overall, 5.8% (n = 44) of patients exhibited CNS-C. Seizures at presentation occurred in 33 patients with COVID-19 (4.4%), with 2.6% (n = 20) experiencing nonfebrile seizures, 1.1% (n = 8) febrile seizures, and 0.7% (n = 5) status epilepticus. More patients with CNS-C experienced seizures during the Omicron wave versus the pre-Omicron period (77.8% vs 41.2%, P = 0.03). Fewer patients were admitted to the intensive care unit in the Omicron wave (7.4%) versus prior waves (7.4% vs 41.2%, P = 0.02). Fewer patients with SARS-CoV-2 experienced CNS-C (5.8%) versus patients with influenza (9.9%), P = 0.03. More patients with SARS-CoV-2 experienced nonfebrile seizures (2.6% vs 0.6%, P = 0.06), whereas more patients with influenza experienced febrile seizures (7.3% vs 1.1%, P < 0.01). CONCLUSIONS: The Omicron wave was characterized by more seizures and fewer intensive-care-unit admissions than previous waves. Pediatric patients with SARS-CoV-2 experienced fewer CNS-C and more nonfebrile seizures compared with patients with influenza.

Severity of excessive gestational weight gain and risk of severe maternal morbidity.

BACKGROUND: Both obesity and excessive gestational weight gain are associated with severe maternal morbidity, but there is limited literature evaluating whether the risk of severe maternal morbidity is further increased by the degree or severity of excessive gestational weight gain. OBJECTIVE: This study aimed to determine whether pregnant patients with excessive gestational weight gain who gained more than 50 lb were at increased risk of severe maternal morbidity compared with those who only moderately exceeded recommended gestational weight gain guidelines. A secondary objective was to determine whether patients who gained 10 lb more than the recommended upper limit of total weight gain for a given prepregnancy body mass index group were at increased risk of severe maternal morbidity compared with those who exceeded that upper limit by a lesser amount. STUDY DESIGN: This was a retrospective cohort study of all patients with live, term, singleton deliveries with excessive gestational weight gain from 7 hospitals within a large health system in New York between January 2019 and February 2020. Excessive gestational weight gain was defined as exceeding the recommended upper limit of total weight gain for a given prepregnancy body mass index category using the National Academy of Medicine gestational weight gain guidelines: >40 lb for a body mass index of <18.5 kg/m2, >35 lb for a body mass index of 18.5 to 24.9 kg/m2, >25 lb for a body mass index of 25.0 to 29.9 kg/m2, and >20 lb for a body mass index of ³30.0 kg/m2. Patient height and weight data were self-reported at the time of delivery hospitalization and retrieved from the electronic medical record system. Patients were classified into 2 excessive gestational weight gain groups: moderate (≤50 lb) or severe (>50 lb). Patients with missing body mass index or gestational weight gain were excluded. The primary exposure was severe excessive gestational weight gain. The primary outcome was severe maternal morbidity, defined using the Centers for Disease Control and Prevention criteria. Logistic regression was used to model the likelihood of severe maternal morbidity, adjusting for race and ethnicity, nulliparity, advanced maternal age, gestational diabetes mellitus, and maternal mood disorder. For the secondary analysis, severe maternal morbidity rates were compared between patients who exceeded their body mass index-specific upper limit of total weight gain by ≥10 lb and those who exceeded it by <10 lb. RESULTS: A total of 11,506 patients were included for analysis, and 1965 patients (17.1%) had severe excessive gestational weight gain. The overall rate of severe maternal morbidity was 3.3%. Severe maternal morbidity occurred in 85 of 1965 patients (4.3%) with severe excessive gestational weight gain and 292 of 9541 patients (3.1%) with moderate excessive gestational weight gain. On regression analysis, after adjustment for covariate factors, patients with a severe excessive gestational weight gain were 39% more likely to experience severe maternal morbidity than those with moderate excessive gestational weight gain (adjusted odds ratio, 1.39; 95% confidence interval, 1.08-1.79). Patients with excessive gestational weight gain of ≥10 lb above the recommended body mass index-specific upper limit for gestational weight gain were 32% more likely (adjusted odds ratio, 1.32; 95% confidence interval, 1.07-1.62) to experience severe maternal morbidity than patients who exceeded that upper limit by <10 lb. CONCLUSION: Patients with live, term, singleton pregnancies who gain more than 50 lb are at increased risk of severe maternal morbidity compared with those who only moderately exceed gestational weight gain guidelines. Similarly, patients who gain ≥10 lb above the recommended body mass index-specific upper limit for gestational weight gain are at increased risk. Further study is warranted to determine the most effective interventions to manage gestational weight gain and mitigate maternal risk.

Vaginal microflora following the use of a disposable home-use vaginal device and a commercially available ring pessary for pelvic organ prolapse management: a randomized controlled trial.

PURPOSE: To investigate whether ProVate, a novel, disposable, self-inserted vaginal device for pelvic organ prolapse management, clinically affects the vaginal microflora, as compared with a commercially available ring pessary, to assess its microbiological safety. METHODS: This interventional, prospective, multi-center, open-label, randomized, controlled, statistically powered (noninferiority), home-use, crossover study was conducted at seven sites. Participants were randomized into either group A (using ProVate and then a new reusable commercially available ring pessary [control]) or B (using control device and then ProVate) with a 1:1 ratio. Noninferiority of ProVate over the control was evaluated for the primary endpoint, which was based on meeting one of the failure criteria: significant change in Lactobacillus spp., Gardnerella vaginalis, Candida morphotypes, or Staphylococcus aureus levels compared to the baseline (significant change: Nugent score ≥ 7 or > 1 scale unit increase in S. aureus or Candida morphotype), bothersome vaginal infection symptoms, or symptoms requiring treatment for infection. RESULTS: The study included 58 participants (mean age: 64.5 years, 91.4% postmenopausal). There were no significant microfloral changes in terms of the four microorganisms mentioned above, the rate of Nugent score ≥ 7 after use was low and comparable between the two devices, and the rate of patients with a > 1 unit-scale change (increase or decrease) from the baseline to the end-of-use phase in any studied microorganism was comparable between the devices. The failure rate was 15.5% for ProVate and 15.5% for control while using 383 ProVate devices over 1647 days or one control device throughout the study. Two patients had bothersome vaginal complaints and one had overt vaginal infection in the control group, but no such cases were observed in the ProVate group. CONCLUSION: The primary endpoint of possible vaginal microbial changes, bothersome vaginal symptoms, or treatment-requiring vaginal complaints while using ProVate was successfully met. Our findings show that the vaginal microflora is comparable when using either ProVate or commercially available ring pessary (control) with a relatively low rate of vaginal infections. Trial registration details: ClinicalTrials.gov; URL: https://www. CLINICALTRIALS: gov/ct2/show/NCT03345121?term=NCT03345121&draw=2&rank=1 ; No. NCT03345121; Registration date, November 17, 2017; initial enrollment started on August 20, 2017.

Fetal hypertrophic cardiomyopathy with elevated middle cerebral artery peak systolic velocity (MCA PSV): A potentially grim association.

An elevated middle cerebral artery peak systolic velocity (MCA PSV) in the setting of nondiabetic hypertrophic cardiomyopathy may portend an especially poor prognosis.

Cocirculation of A(H3N2) and B/Victoria increased morbidity in hospitalized patients in the 2019-2020 A(H1N1)pdm09 predominant influenza season in Israel.

Community surveillance found the 2019-2020 A(H1N1)pdm09 predominant influenza season in Israel to be a high-intensity season with an early and steep morbidity peak. To further characterize disease severity in the 2019-2020 season, we analyzed a cohort of hospitalized patients with laboratory-confirmed influenza from this season (n = 636). Quantitative polymerase chain reaction was performed on clinical samples to detect the presence of influenza. Demographic, clinical, and laboratory data were retrieved via electronic health records and MDClone. Electronic health records were accessed to obtain data on intensive care unit patients, missing data and for data verification purposes. Univariate analysis was performed to compare demographic, comorbidity, and clinical characteristics across the three influenza strains. The A(H1N1)pdm09 predominant 2019-2020 influenza season in Israel was characterized by an early and steep morbidity peak, vaccine delays and shortages, and with the A(H3N2) and B/Victoria strains disproportionately targeting children and young adults, most probably due to reduced immunity to these strains. A greater proportion of children <5 years infected with A(H3N2) and B/Victoria developed severe influenza compared with those infected with A(H1N1)pdm09. Our study emphasizes the vulnerability of infants and young children in the face of rapidly evolving influenza strains and underscores the importance of influenza prevention measures in this population.

Virtual Reality "exergames": A promising countermeasure to improve motivation and restorative effects during long duration spaceflight missions.

Long duration spaceflight missions will require novel exercise systems to protect astronaut crew from the detrimental effects of microgravity exposure. The SPRINT protocol is a novel and promising exercise prescription that combines aerobic and resistive training using a flywheel device, and it was successfully employed in a 70-day bed-rest study as well as onboard the International Space Station. Our team created a VR simulation to further augment the SPRINT protocol when using a flywheel ergometer training device (the Multi-Mode Exercise Device or M-MED). The simulation aspired to maximal realism in a virtual river setting while providing real-time biometric feedback on heart rate performance to subjects. In this pilot study, five healthy, male, physically-active subjects aged 35 ± 9.0 years old underwent 2 weeks of SPRINT protocol, either with or without the VR simulation. After a 1-month washout period, subjects returned for a subsequent 2 weeks in the opposite VR condition. We measured physiological and cognitive variables of stress, performance, and well-being. While physiological effects did not suggest much difference with the VR condition over 2 weeks, metrics of motivation, affect, and mood restoration showed detectable differences, or trended toward more positive outcomes than exercise without VR. These results provide evidence that a well-designed VR "exergaming" simulation with biometric feedback could be a beneficial addition to exercise prescriptions, especially if users are exposed to isolation and confinement.

Thrombocytopenia and Bloodstream Infection: Incidence and Implication on Length of Stay in the Pediatric Intensive Care Unit.

The incidence and prognosis of thrombocytopenia in critically ill patients with bloodstream infection (BSI) is not well delineated in the pediatric intensive care unit (PICU) setting. We assessed these variables in our PICU and sought to determine whether thrombocytopenia could serve as a prognostic marker for length of stay (LOS). The study was conducted at the medical PICU of a university hospital, on all critically ill pediatric patients consecutively admitted during a 3-year period. Patient surveillance and data collection have been used to identify the risk factors during the study period. The main outcomes were BSI incidence and implication on morbidity and LOS. Data from 2,349 PICU patients was analyzed. The overall incidence of BSI was 3.9% (93/2,349). Overall, 85 of 93 patients (91.4%) with BSI survived and 8 patients died (8.6% mortality rate). The overall incidence of thrombocytopenia among these 93 patients was 54.8% (51/93) and 100% (8/8) for the nonsurvivors. Out of the 85 survivors, 27 thrombocytopenic patients were hospitalized for >14 days versus 14 of nonthrombocytopenic patients ( p = 0.007). Thrombocytopenia was associated with borderline significance with an increased LOS (adjusted odds ratio = 3.00, 95% confidence interval: 0.93-9.71, p = 0.066). Thrombocytopenia is common in critically ill pediatric patients with BSI and constitutes a simple and readily available risk marker for PICU LOS.

Gravitational Dose-Response Curves for Acute Cardiovascular Hemodynamics and Autonomic Responses in a Tilt Paradigm.

Background The cardiovascular system is strongly dependent on the gravitational environment. Gravitational changes cause mechanical fluid shifts and, in turn, autonomic effectors influence systemic circulation and cardiac control. We implemented a tilt paradigm to (1) investigate the acute hemodynamic response across a range of directions of the gravitational vector, and (2) to generate specific dose-response relationships of this gravitational dependency. Methods and Results Twelve male subjects were tilted from 45° head-up tilt to 45° head-down tilt in 15° increments, in both supine and prone postures. We measured the steady-state hemodynamic response in a range of variables including heart rate, stroke volume, cardiac output, oxygen consumption, total peripheral resistance, blood pressure, and autonomic indices derived from heart rate variability analysis. There is a strong gravitational dependence in almost all variables considered, with the exception of oxygen consumption, whereas systolic blood pressure remained controlled to within ≈3% across the tilt range. Hemodynamic responses are primarily driven by differential loading on the baroreflex receptors, combined with differences in venous return to the heart. Thorax compression in the prone position leads to reduced venous return and increased sympathetic nervous activity, raising heart rate, and systemic vascular resistance while lowering cardiac output and stroke volume. Conclusions Gravitational dose-response curves generated from these data provide a comprehensive baseline from which to assess the efficacy of potential spaceflight countermeasures. Results also assist clinical management of terrestrial surgery in prone posture or head-down tilt positions.

Outbreak of Influenza and Other Respiratory Viruses in Hospitalized Patients Alongside the SARS-CoV-2 Pandemic.

Influenza A and other respiratory viruses, circulate each winter and cause respiratory illness that can lead to severe complications in hospitalized patients. During the COVID-19 pandemic, only a few cases of respiratory viruses were detected in Israel. Our study applied RT-PCR to examine 13,674 samples collected from patients hospitalized with respiratory symptoms in 2019, 2020, and 2021 and the first half of the 2022 winter. A sharp increase in influenza A(H3N2) cases was observed in winter 2021-2022 as compared to 2020, followed by a sudden decrease in influenza cases after the detection of the SARS-CoV-2 omicron variant in Israel. Comparison of the area under the curve (AUC) of influenza infection rates during 7 consecutive winter seasons found that the minimal AUC between 2015 and 2020 was 281.1, while in 2021-2022, it was significantly lower (162.6 AUC; p = 0.0017), although the percentage of positive influenza cases was similar to those of previous years. The presented findings show how the dominance of influenza A(H3N2) abruptly ended upon circulation of the SARS-CoV-2 omicron variant. However, a post-COVID-19 influenza outbreak is possible, hence the planning of the next influenza vaccine is critical to ensure lower influenza-related hospitalization rates.

Reducing Metabolic Cost During Planetary Ambulation Using Robotic Actuation.

INTRODUCTION: Current spacesuits are cumbersome and metabolically expensive. The use of robotic actuators could improve extravehicular activity performance. We propose a novel method to quantify the benefit of robotic actuators during planetary ambulation.METHODS: Using the OpenSim framework, we completed a biomechanical analysis of three walking conditions: unsuited, suited with the extravehicular mobility unit (EMU) spacesuit (represented as external joint torques applied to human joints), and suited with the EMU and assisted by robotic actuators capable of producing up to 10 Nm of torque. For each scenario, we calculated the inverse kinematics and inverse dynamics of the lower body joints (hip, knee, and ankle). We also determined the activation of muscles and robotic actuators (when present). Finally, from inverse dynamics and muscle activation results, the metabolic cost of one gait cycle was calculated in all three conditions.RESULTS: The moments of lower body joints increased due to the increased resistance to movement from the spacesuit. The additional torque increased the overall metabolic cost by 85 compared to the unsuited condition. The assistive robotic actuators were able to reduce the metabolic cost induced by EMU resistance by 15.DISCUSSION: Our model indicates that the majority of metabolic cost reduction can be attributed to the actuators located at the hip. The robotic actuators reduced metabolic cost similar to that of modern-day actuators used to improve walking. During a Mars mission, the actuators could save one crewmember up to 100,000 kilocal on one 539-d planetary expedition.Kluis L, Keller N, Bai H, Iyengar N, Shepherd R, Diaz-Artiles A. Reducing metabolic cost during planetary ambulation using robotic actuation. Aerosp Med Hum Perform. 2021; 92(7):570578.

The Influence of Altered-Gravity on Bimanual Coordination: Retention and Transfer.

Many of the activities associated with spaceflight require individuals to coordinate actions between the limbs (e.g., controlling a rover, landing a spacecraft). However, research investigating the influence of gravity on bimanual coordination has been limited. The current experiment was designed to determine an individual's ability to adapt to altered-gravity when performing a complex bimanual force coordination task, and to identify constraints that influence coordination dynamics in altered-gravity. A tilt table was used to simulate gravity on Earth [90° head-up tilt (HUT)] and microgravity [6° head-down tilt (HDT)]. Right limb dominant participants (N = 12) were required to produce 1:1 in-phase and 1:2 multi-frequency force patterns. Lissajous information was provided to guide performance. Participants performed 14, 20 s trials at 90° HUT (Earth). Following a 30-min rest period, participants performed, for each coordination pattern, two retention trials (Earth) followed by two transfer trials in simulated microgravity (6° HDT). Results indicated that participants were able to transfer their training performance during the Earth condition to the microgravity condition with no additional training. No differences between gravity conditions for measures associated with timing (interpeak interval ratio, phase angle slope ratio) were observed. However, despite the effective timing of the force pulses, there were differences in measures associated with force production (peak force, STD of peak force mean force). The results of this study suggest that Lissajous displays may help counteract manual control decrements observed during microgravity. Future work should continue to explore constraints that can facilitate or interfere with bimanual control performance in altered-gravity environments.

Military transgender care.

Transgender individuals have a long-standing history of honorable service in the United States Military. However, politics have had an impact on their ability to openly serve in uniform as policies continually change rapidly with each new administration. This article describes the shifting political landscape of policies related to whether (or not) transgender individuals can serve in the military, and how this has affected the health care experiences of transgender individuals and the ability for nurse practitioners to provide quality health care to the transgender population serving on active duty.

Adenovirus load correlates with respiratory disease severity among hospitalized pediatric patients.

OBJECTIVES: Human adenoviruses (HAdVs) are common pathogens that can cause respiratory, gastrointestinal and other infections. We investigated the correlation between adenovirus viral load in clinical respiratory samples and the respiratory disease severity in pediatric patients. METHODS: Medical records of patients hospitalized in the Sheba Medical Center (SMC) with confirmed adenovirus infection were retrospectively analyzed. The possible correlation between disease severity score and Real time PCR 'cycle threshold' (Ct), a proxy of viral load, was assessed in patients aged 9 years and under. In addition, Ct values of hospitalized versus community-care patient samples, positive for various respiratory viruses including adenovirus, were compared. RESULTS: Adenovirus load in respiratory samples, as measured by Ct values, was found to be negatively correlated with respiratory disease severity in hospitalized pediatric patients aged under 9 years. Moreover, hospitalized patients presented with significantly higher Ct levels for various respiratory viruses as compared to community-care patients. CONCLUSION: In this study we found a correlation between Ct values obtained from adenovirus q-PCR analysis of respiratory clinical samples and disease severity in patients aged 9 years and under. Such finding may serve as a predictor of respiratory disease course in pediatric patients and will be beneficial for the differential diagnosis and treatment of pediatric patients.

Treatment Outcomes of Stenotrophomonas maltophilia Bacteremia in Critically Ill Children: A Multicenter Experience.

OBJECTIVES: Stenotrophomonas maltophilia is a gram-negative opportunistic bacterium that may cause a myriad of clinical diseases in immunocompromised individuals. We aimed to describe the clinical characteristics, risk factors, mortality, and treatment of S. maltophilia bacteremia in critically ill children, a topic on which data are sparse. DESIGN: A multicenter observational retrospective study in which medical charts of critically ill children with S. maltophilia bacteremia were reviewed between 2012 and 2017. SETTING: Data were collected from each of the four largest PICUs nationwide, allocated in tertiary medical centers to which children with complex conditions are referred regularly. PATIENTS: A total of 68 suitable cases of S. maltophilia bacteremia were retrieved and reviewed. MEASUREMENTS AND MAIN RESULTS: The total occurrence rate of S. maltophilia isolation had increased significantly during the study period (r = 0.65; p = 0.02). The crude mortality was 42%, and the attributed mortality was 18%. Significant risk factors for mortality were a longer length of hospital stay prior to infection (33 d in nonsurvivors vs 28 in survivors; p = 0.03), a nosocomial source of infection (p = 0.02), presentation with septic shock (p < 0.001), and treatment with chemotherapy (p = 0.007) or carbapenem antibiotics (p = 0.05) prior to culture retrieval. On multivariate analysis, septic shock (odds ratio, 14.6; 95% CI, 1.45-147.05; p = 0.023) and being treated with chemotherapy prior to infection (odds ratio, 5.2; 95% CI, 1.59-17.19; p = 0.006)] were associated with mortality. The combination of ciprofloxacin, trimethoprim-sulfamethoxazole, and minocycline resulted in the longest survival time (p < 0.01). CONCLUSIONS: The significant attributed mortality associated with S. maltophilia bacteremia in critically ill children calls for an aggressive therapeutic approach. The findings of this investigation favor a combination of trimethoprim-sulfamethoxazole, ciprofloxacin, and minocycline.

Risk analysis of antimicrobial resistance in outpatient urinary tract infections of young healthy adults.

Objectives: Most studies addressing community-acquired urinary tract infections (UTIs) pertain to mixed cohorts, in which young healthy adults are under-represented. We aimed to dissect the intricate interrelation between exposures and subsequent antimicrobial resistance (AMR) patterns in a unique setting of young healthy adults, allowing further guidance in this group. Methods: We carried out a retrospective cross-sectional study of all Enterobacteriaceae-associated outpatient UTIs during 2014-16 in soldiers, representing the young fit population in Israel. Electronic medical records were reviewed for demographic and clinical data, antimicrobial exposures and prescriptions. Risk factors for AMR were analysed by multivariate logistic regression. Results: Of 1207 cases, 1144 (94.8%) were females, with a median age of 20.2 years. Escherichia coli was the predominant species (83.2%). Only 686 (56.8%) isolates were fully susceptible. AMR rates were as follows: trimethoprim/sulfamethoxazole, 19.6%; oral cephalosporins, 9.7%-16.7%; amoxicillin/clavulanate, 12.1%; ciprofloxacin, 11.1%; and nitrofurantoin, 12.6%. Predictors of AMR were recurrent UTIs, past-year hospitalization, male gender and non E. coli strains. Antimicrobials prescribed >6 months preceding the culprit infection were not related to AMR. Fluoroquinolone and cephalosporin exposures were highly predictive of further AMR, yet nitrofurantoin and, to a lesser extent, amoxicillin/clavulanate had fewer associations with AMR induction and resistance to these antimicrobials was less associated with any exposure. Conclusions: This nationwide study of community-related UTIs shows significant AMR rates for commonly used oral antimicrobials even in young fit adults. Nitrofurantoin proved once more to be an adequate empirical choice regardless of previous exposures, having a less detrimental effect on future AMR. Conversely, both resistance to fluoroquinolones following previous exposures and the associated heavy ecological burden should deter their common use as first-line agents for UTIs.

Successful treatment of invasive mucormycosis with isavuconazole in pediatric patients.

BACKGROUND: Invasive mold infections (IMIs) are a leading cause of mortality among immunocompromised patients. Isavuconazole is a new drug that shows promise in the adult population for the treatment of IMIs. No data regarding the use of isavuconazole in pediatric patients have been published. METHODS: Patients with a diagnosis of IMI from our pediatric hemato-oncology division, treated with isavuconazole between 2010 and 2016, were identified using the hospital's computerized database. Data including demographics, clinical course, and outcome were collected. Pharmacokinetic samples were obtained from two younger patients to guide dosing. RESULTS: In total, three patients (4.5, 5, and 19 years of age) with invasive mucormycosis who were treated with isavuconazole were identified. All patients were treated with isavuconazole as a second line therapy and experienced improvement following the initiation of this treatment. CONCLUSIONS: Based on our limited clinical experience, isavuconazole may be a safe and effective treatment option for children and adolescents afflicted by IMI. Prospective clinical trials should be performed in order to evaluate the pharmakokinetics and safety of isavuconazole in the pediatric population.

Management of sexually transmissible infections in the era of multiplexed molecular diagnostics: a primary care survey.

Background Data regarding sexually transmissible infections (STI) often originate from STI clinics, screening programs or laboratory-based studies, thus are biased for specific risk groups or lack clinical details. This real-life observational study presents sample data of most young adult Israeli population by exploiting the centralised diagnostic and documentation platforms resulting from a mandatory military service at the age of 18 years for both genders. METHODS: All STI diagnoses of Israeli Defence Forces soldiers during a 6-month period were reviewed. Patients with Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) (major-STI) and Ureaplasma urealyticum (UU), Ureaplasma parvum (UP) and Mycoplasma hominis (MH) (equivocal STI) were compared with STI-negative controls. RESULTS: Sexually transmissible infection positivity rates (n=2816) were as follows: CT 6.6%; MG 1.9%; NG 0.7%; TV 0.5%; UU 15.7%; UP 28.2%; and MH 6.2%. The CT+MG coinfection rate was 4.1%, yet CT+NG coinfections were rare (≈0.5%). More than half of the patients with ureaplasmas and/or MH were treated; 40% of them were recommended partner treatment. Most antibiotics were prescribed to patients with equivocal infections. Classic STI symptoms in males were linked to major-STI and UU, while females were asymptomatic or presented non-specific symptoms. CONCLUSIONS: The judicious use of antibiotics in the era of antimicrobial resistance necessitates re-evaluating the significance of equivocal pathogen detection and reporting (MH, UU, UP). Likewise, universal empiric treatment for NG should be reconsidered in light of its low rates in non-high-risk groups. Conversely, a high MG rate, a pathogen with potential resistance to common STI protocols, requires evaluation of guidelines adequacy.