Awaking the dormant virome in the rhizosphere.

The rhizosphere is a vital soil compartment providing key plant-beneficial functions. However, little is known about the mechanisms driving viral diversity in the rhizosphere. Viruses can establish lytic or lysogenic interactions with their bacterial hosts. In the latter, they assume a dormant state integrated in the host genome and can be awakened by different perturbations that impact host cell physiology, triggering a viral bloom, which is potentially a fundamental mechanism driving soil viral diversity, as 22%-68% of soil bacteria are predicted to harbour dormant viruses. Here we assessed the viral bloom response in rhizospheric viromes by exposing them to three contrasting soil perturbation agents: earthworms, herbicide and antibiotic pollutant. The viromes were next screened for rhizosphere-relevant genes and also used as inoculant on microcosms incubations to test their impacts on pristine microbiomes. Our results show that while post-perturbation viromes diverged from control conditions, viral communities exposed to both herbicide and antibiotic pollutant were more similar to each other than those influenced by earthworms. The latter also favoured an increase in viral populations harbouring genes involved in plant-beneficial functions. Post-perturbation viromes inoculated on soil microcosms changed the diversity of pristine microbiomes, suggesting that viromes are important components of the soil ecological memory driving eco-evolutionary processes that determine future microbiome trajectories according to past events. Our findings demonstrate that viromes are active players in the rhizosphere and need to be considered in efforts to understand and control the microbial processes towards sustainable crop production.

Trends in Neonatal Extracorporeal Membrane Oxygenation During a Venovenous Cannula Shortage.

OBJECTIVES: To report temporal trends in venovenous extracorporeal membrane oxygenation (ECMO) use for neonatal respiratory failure in U.S. centers before and after functional venovenous cannula shortage due to withdrawal of one dual lumen venovenous cannula from the market in 2018. DESIGN: Retrospective cohort study. SETTING: ECMO registry of the Extracorporeal Life Support Organization. PATIENTS: Infants who received neonatal (cannulated prior to 29 d of age) respiratory ECMO at a U.S. center and had a record available in the ECMO registry from January 1, 2010 to July 20, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was receipt of venovenous ECMO (vs venoarterial or other), and secondary outcomes were survival to hospital discharge and adverse neurologic outcomes. Using an interrupted time series design, we fit multivariable mixed effects logistic regression models with receipt of venovenous ECMO as the dependent variable, treatment year modeled as a piecewise linear variable using three linear splines (pre shortage: 2010-2014, 2014-2018; shortage: 2018-2021), and adjusted for center clustering and multiple covariates. We evaluated trends in venovenous ECMO use by primary diagnosis including congenital diaphragmatic hernia, meconium aspiration, pulmonary hypertension, and other. Annual neonatal venovenous ECMO rates decreased after 2018: from 2010 to 2014, adjusted odds ratio (aOR) for yearly trend 0.98 (95% CI 0.92-1.04), from 2014 to 2018, aOR for yearly trend 0.90 (95% CI 0.80-1.01), and after 2018, aOR for yearly trend 0.46 (95% CI 0.37-0.57). We identified decreased venovenous ECMO use after 2018 in all diagnoses evaluated, and we failed to identify differences in temporal trends between diagnoses. Survival and adverse neurologic outcomes were unchanged across the study periods. CONCLUSIONS: Venovenous ECMO for neonatal respiratory failure in U.S. centers decreased after 2018 even after accounting for temporal trends, coincident with withdrawal of one of two venovenous cannulas from the market.

Pulmonary Support of Infants with Tracheotomies in a Regional Neonatal Intensive Care Unit.

OBJECTIVE: We evaluate patient characteristics, hospital course, and outcome by type discharge pulmonary support; mechanical ventilation (MV) or with tracheotomy masks (TM). STUDY DESIGN: We reviewed records of infants admitted to the neonatal intensive care unit (NICU) that underwent tracheotomy within their first year of life between 2006 and 2017. We evaluated patient characteristics, referral pattern, destination of discharge, and outcome by type of pulmonary support at discharge (MV vs. TM). RESULTS: Of the 168 patients, 63 (38%) were inborn, 91 (54%) transferred to our NICU, and 5 (3%) were readmitted after being home. Median gestational age at birth was 34 weeks. Twenty-three (14%) infants were transferred to hospitals closer to their homes (13 with MV and 10 with TM), and 125 (74%) were discharged home (75 on MV and 50 on TM). Twenty patients (12%) died in the regional center (RC). Among those discharged home from our RC, infants on MV were of lower birth weight and younger gestational age, had tracheostomies later in life, had longer duration between tracheostomy to discharge to home, and had longer total duration of hospitalization at the RC. In addition, infants in the MV group were more frequently dependent on MV at time of placement of tracheostomies, less frequently had congenital airway anomalies and more frequently having possibly acquired airway anomalies and more frequently having major congenital anomalies, more frequently treated with diuretics, inhaled medications and medications for pulmonary hypertension, and more frequently had gastrostomies for feeding compared with the TM group. CONCLUSION: Patients with tracheostomies in the NICU and discharged from RC on MV or TM vary by patient characteristic, timing of tracheostomy placement, timing of discharge from RC, type of upper airway anomalies, duration of stay in the hospital, and complexity of medical condition at discharge. KEY POINTS: · Infants on home mechanical ventilation have long hospital stay and complex conditions at discharge.. · We describe factors associated with the type of pulmonary support for infants with tracheostomies.. · Treatment strategy may influence type of discharge pulmonary support in infants with tracheostomies..

Structure and Antimicrobial Activity of Rare Lactone Lipids from the Sooty Mold (Scorias spongiosa).

Two new lactone lipids, scoriosin (1) and its methyl ester (2), with a rare furylidene ring joined to a tetrahydrofurandione ring, were isolated from Scorias spongiosa, commonly referred to as sooty mold. The planar structure of these compounds was assigned by 1D and 2D NMR. The conformational analysis of these molecules was undertaken to evaluate the relative and absolute configuration through GIAO NMR chemical shift analysis and ECD calculation. In addition to the potent antimicrobial activities, compound 2 strongly potentiated the activity of amphotericin B against Cryptococcus neoformans, suggesting the potential utility of this compound in combination therapies for treating cryptococcal infections.

A Preclinical Safety Study of Thyroid Hormone Instilled into the Lungs of Healthy Rats-an Investigational Therapy for ARDS.

Acute respiratory distress syndrome (ARDS) is a severe, life-threatening form of respiratory failure characterized by pulmonary edema, inflammation, and hypoxemia due to reduced alveolar fluid clearance (AFC). Alveolar fluid clearance is required for recovery and effective gas exchange, and higher rates of AFC are associated with reduced mortality. Thyroid hormones play multiple roles in lung function, and L-3,5,3'-triiodothyronine (T3) has multiple effects on lung alveolar type II cells. T3 enhances AFC in normal adult rat lungs when administered intramuscularly and in normal or hypoxia-injured lungs when given intratracheally. The safety of a commercially available formulation of liothyronine sodium (synthetic T3) administered intratracheally was assessed in an Investigational New Drug Application-enabling toxicology study in healthy rats. Instillation of the commercial formulation of T3 without modification rapidly caused tracheal injury and often mortality. Intratracheal instillation of T3 that was reformulated and brought to a neutral pH at the maximum feasible dose of 2.73 µg T3 in 300 µl for 5 consecutive days had no clinically relevant T3-related adverse clinical, histopathologic, or clinical pathology findings. There were no unscheduled deaths that could be attributed to the reformulated T3 or control articles, no differences in the lung weights, and no macroscopic or microscopic findings considered to be related to treatment with T3. This preclinical safety study has paved the way for a phase I/II study to determine the safety and tolerability of a T3 formulation delivered into the lungs of patients with ARDS, including coronavirus disease 2019-associated ARDS, and to measure the effect on extravascular lung water in these patients. SIGNIFICANCE STATEMENT: There is growing interest in treating lung disease with thyroid hormone [triiodothyronine (T3)] in pulmonary edema and acute respiratory distress syndrome (ARDS). However, there is not any published experience on the impact of direct administration of T3 into the lung. An essential step is to determine the safety of multiple doses of T3 administered in a relevant animal species. This study enabled Food and Drug Administration approval of a phase I/II clinical trial of T3 instillation in patients with ARDS, including coronavirus disease 2019-associated ARDS (T3-ARDS ClinicalTrials.gov Identifier NCT04115514).

Novel N-1 substituted fluoroquinolones inhibit human topoisomerase I activity and exhibit anti-proliferative activity.

Fluoroquinolone-class agents selectively target the bacterial type IIA topoisomerases DNA gyrase and topoisomerase IV, with a few exceptions that target eukaryotic type IIA topoisomerases. Fluoroquinolones bind and stabilize type IIA topoisomerase-DNA covalent complexes that contain a double-strand break. This unique mode of action is referred to as 'topoisomerase poisoning'. We discovered that two novel fluoroquinolones having aryl functionality at the N-1 position, UITT-3-217 (217) and UITT-3-227 (227), could inhibit the catalytic activity of human topoisomerase II without stabilizing topoisomerase-DNA complexes, i.e., without poisoning it. Surprisingly, these compounds are more effective in inhibiting the catalytic activities of human and bacterial topoisomerase I. The National Cancer Institute's 60 human tumor cell lines screen revealed significant anti-proliferative activities with 217 and 227 against the majority of 60 cancer cell lines. A proof of concept in vivo efficacy study using an HT-29 xenograft model of human colorectal cancer showed that 217 could inhibit the proliferation of human colorectal cancer cells to a degree comparable to fluorouracil in mice. Although 227 also exhibited anti-proliferative activity, it was not as effective as 217 in this xenograft model. These novel fluoroquinolones may serve as promising lead compounds for the development of new anticancer drugs.

Clinical and microbiologic investigation of an expedited peri-implantitis dog model: an animal study.

BACKGROUND: Animal studies are pivotal in allowing experimentation to identify efficacious treatment protocols for resolution of peri-implantitis. The purpose of this investigation was to characterize an expedited dog peri-implantitis model clinically, radiographically, and microbiologically. METHODS: Eight hound dogs underwent extractions (week 0) and implant (3.3 × 8.5 mm) placement with simultaneous surgical defect creation and ligature placement for induction of peri-implantitis (week 10). Ligatures were replaced at 6 weeks (week 16) and removed after 9 weeks (week 19) when supporting bone loss involved approximately 50% of the peri-implant bone. Microbial samples from the defects and healthy control implant sites collected at week 19 were analyzed utilizing a microarray. Clinical measures of inflammation were obtained and radiographic bone loss was measured from periapical radiographs. Radiographic depth and width measurements of bony defect were repeated at weeks 10 (baseline), 16, and 19. Canonical analysis of principal coordinates was used to visualize overall differences in microbial abundance between peri-implantitis and healthy implants. RESULTS: This accelerated disease protocol led to intrabony defect creation with a mean depth and width of 4.3 mm and 3.5 mm, respectively after 9 weeks of ligature placement. Microbial identification revealed 59 total bacteria in peri-implant sites, 21 of which were only present in peri-implant sites as compared to healthy controls. Overall microbial beta diversity (microbial between-sample compositional diversity) differed between peri-implantitis and healthy implants (p = 0.009). CONCLUSIONS: Within the limitations of this study, this protocol led to expedited generation of peri-implant defects with a microbial profile indicative of a shift to disease and defect patterns conducive to regenerative treatment. However, the possibility of potential spontaneous resolution of lesions due to the lack of a chronicity interval as compared to chronic disease models need to be further clarified and considered during preclinical peri-implantitis model selection.

Lumbar Punctures at an Academic Level 4 NICU: Indications for a New Curriculum.

ISSUE: Pediatric residents commonly perform lumbar punctures during their clinical training. The objective of this study was to assess residents' rate of nontraumatic lumbar punctures, examine the adequacy of samples, and implement proper documentation of the procedure in an academic Level 4 Neonatal Intensive Care Unit. We hypothesize that traumatic taps are common and that documentation of the procedure is poor. EVIDENCE: A retrospective chart review was done of infants admitted to the neonatal intensive care unit from January 2011 to November 2011 who underwent a lumbar puncture. Procedure notes were evaluated for completion of proper documentation, the lab specimen was assessed for red blood cell count less than 1,000 cells/mm(3), and individuals were assessed for their ability to obtain a cerebrospinal fluid sample to send to the lab for analysis (i.e., sample of adequate volume and not clotted) and the total number of attempts to obtain a sample. A total of 184 charts were reviewed. Procedure notes were incomplete (58%) and lacked pertinent details. Eight percent of samples obtained had no record of the procedure being preformed. There was inadequate sample acquisition in 23% of the lumbar punctures. More than three attempts were noted in 14% of lumbar punctures performed. Many specimens contained very high red blood cell counts. Seventy-five percent of lumbar punctures with full documentation (n = 60), resulted in cerebrospinal fluid with more than 1,000 red blood cells/mm(3) and 55% of underdocumented lumbar punctures resulted in cerebrospinal fluid with more than 1,000 red blood cells/mm(3) (n = 71). IMPLICATIONS: We found that poorly documented lumbar punctures are common and the ability of residents to obtain satisfactory cerebrospinal fluid is low. The inability of residents to consistently perform nontraumatic lumbar punctures is likely a common phenomenon. New educational methods and evaluation criteria must be developed to address this gap in resident education.

Effectiveness of a clinical pathway with methadone treatment protocol for treatment of neonatal abstinence syndrome following in utero drug exposure to substances of abuse*.

OBJECTIVE: To evaluate the effectiveness of methadone for the treatment of neonatal abstinence syndrome when used according to a preexisting clinical pathway. DESIGN: This is a 3-year retrospective study conducted at a single institution. In this study, neonates who received methadone for the treatment of neonatal abstinence syndrome according to a predefined clinical treatment pathway were evaluated for treatment success: defined as adherence to the methadone regimen with no residual signs of withdrawal. Data were collected for methadone dosages, Lipsitz scores, length of methadone treatment, total length of hospital stay, and relevant clinical data. SETTING: Level III neonatal ICU. PATIENTS: Newborn infants with in utero exposure to substances of abuse. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty patients were included. The mean gestational age and birth weight were 37.07 ± 3.05 weeks and 2.77 ± 0.6 kg. All 60 patients exhibited neonatal abstinence syndrome within first 72 hours of life. Fifty-seven of 60 patients (95%) initiated methadone treatment according to protocol. There was deviation from the protocol at 48 and 72 hours of treatment with approximately 59% and 13% of the patients still on methadone at more than the prescribed amount to control neonatal abstinence syndrome. The mean ± SD total methadone exposure was 1.99 ± 1.63 mg/kg, length of treatment 11.66 ± 9.02 days, and total hospital length of stay 22.43 ± 29.3 days, suggesting significant variability in response. No significant correlation was found between birth weight or gestational age and length of treatment. CONCLUSION: Clinical pathway for treating neonatal abstinence syndrome was closely followed at the initial diagnosis. The doses of methadone used in the first 24-48 hours of this study were insufficient for adequate symptom control. Despite a formal treatment protocol, there was substantial variability in total methadone exposure, length of treatment, and length of stay, suggesting other contributory factors for the observed variability.

Back Transfer of Infants with Tracheostomies: A Regional Center Experience.

We describe our center's experience with the back transfer of infants following tracheostomies. We conducted a retrospective cohort study of infants transferred to pediatric critical care units of our regional center with conditions originating in the neonatal period who underwent tracheostomy during the hospitalization within their first year of life between 2006 and 2017. Recovering patients are discharged home or transferred back to the referring hospitals. We evaluated patient characteristics, destination of discharge and type of pulmonary support at discharge, and mechanical ventilation (MV) or tracheotomy masks (TM). Of the 139 included patients, 72% were transferred to the neonatal intensive care unit, 21% to the pediatric cardiothoracic unit, and 7% to the pediatric intensive care unit. Their median gestational age was 35 weeks. They were admitted at a median 22 days of life and lived at a median distance of 56 miles from our center. Furthermore, 34 infants (24%) were back transferred closer to their homes (23 with MV and 11 with TM), and 84 (60%) were discharged home (53 on MV and 31 on TM). Twenty-one patients (15%) died in the hospital (before discharge or transfer). Back transferred patients on MV had a significantly shorter duration between tracheostomy and transfer compared with those discharged home from our center: MV (median = 22 vs. 103 days, p < 0.0001) and TM (median = 13 vs. 35 days, p < 0.0001). Back transfer of infants with tracheostomies closer to their homes was associated with a significantly shorter hospitalization and more efficient use of the subspecialized resources at the RC.

Risk of death at home or on hospital readmission after discharge with pediatric tracheostomy.

OBJECTIVE: To evaluate outcomes of patients discharged home following tracheostomy, including the timing and place of death for non-survivors. STUDY DESIGN: We retrospectively reviewed medical records of infants undergoing tracheostomy between 2006 and 2017, within the first year of life for congenital or acquired neonatal conditions. RESULTS: Of the 224 patients discharged after tracheostomy, 127 (57%) required home mechanical ventilation (MV). Overall, 40 (18%) patients died (65% were on MV); 38% of the deaths occurred at home and 63% at a subsequent hospitalization. Having tube feeding was identified as significantly associated with increased mortality on multivariate analysis. Having a tracheostomy for upper airway obstruction was the only variable significantly associated with increased risk of death at home on multivariate analysis. CONCLUSIONS: Having tube feeding was associated with increased risk of death overall and having the tracheostomy for obstructive airway conditions was associated with death occurring at home.

Variation in lumbar punctures for early onset neonatal sepsis: a nationally representative serial cross-sectional analysis, 2003-2009.

BACKGROUND: Whether lumbar punctures (LPs) should be performed routinely for term newborns suspected of having early onset neonatal sepsis (EONS) is subject to debate. It is unclear whether variations in performance of LPs for EONS may be associated with patient, hospital, insurance or regional factors. Our objective was to identify characteristics associated with the practice of performing LPs for suspected EONS in a nationally representative sample. METHODS: Utilizing data from the 2003, 2006 and 2009 Kids' Inpatient Database (KID) compiled by the Agency for Healthcare Research and Quality, we examined the frequency and characteristics of term, normal-birth weight newborns receiving an LP for EONS. Survey-weighting was applied for national estimates and used in chi squared and multivariable regression analysis. RESULTS: In 2009, there were 13,694 discharges for term newborns that underwent LPs for apparent EONS. Newborns having LPs performed were more likely to be covered by Medicaid vs. private insurance (51.9 vs. 45.1 percent; p < 0.001), be born in urban vs. rural hospitals (94.8 vs. 87.3 percent; p < 0.001), teaching vs. non-teaching (60.8 vs. 43.1 percent; p < 0.001) and children's hospitals vs. non-children's (23.0 vs. 11.2 percent; p < 0.001). Lastly, newborns having LPs performed were disproportionately born in the Northeast census region (p = 0.03). In multi-year adjusted analysis, infants with Medicaid coverage, and those born in urban or teaching hospitals, consistently had higher odds of having an LP performed. CONCLUSIONS: We found pronounced variation in LPs performed for EONS, even when adjusting for clinical conditions that would prompt LPs. These findings indicate practice variations in newborn care that merit further examination and explanation.

The effect of late preterm birth on mortality of infants with hypoplastic left heart syndrome.

OBJECTIVES: We evaluated the effect of late preterm (34 to 36 weeks' gestation) delivery on hospital mortality of infants with hypoplastic left heart syndrome (HLHS). STUDY DESIGN: Retrospective review of records of infants born at or after 34 weeks with no other lethal anomalies, cared for in a single tertiary perinatal center between 2002 and 2009. Factors associated with death prior to discharge from the hospital were ascertained using univariate and multivariate analyses. RESULTS: Of the 243 infants with HLHS, 35 were late preterm and 208 were ≥37 weeks (term). Using logistic regression analysis, late preterm delivery (odds ratio [OR] 2.95; 95% confidence interval [CI] 1.35 to 6.45), the presence of other major cardiac defects (OR 3.76; 95% CI 1.31 to 10.81), and the presence of noncardiac congenital anomalies (OR 6.13; 95% CI 1.43 to 26.22) were independently associated with hospital death. CONCLUSION: Late preterm birth of infants with HLHS was independently associated with an increased risk of hospital death compared with those delivered at term.

Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009.

CONTEXT: Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome primarily caused by maternal opiate use. No national estimates are available for the incidence of maternal opiate use at the time of delivery or NAS. OBJECTIVES: To determine the national incidence of NAS and antepartum maternal opiate use and to characterize trends in national health care expenditures associated with NAS between 2000 and 2009. DESIGN, SETTING, AND PATIENTS: A retrospective, serial, cross-sectional analysis of a nationally representative sample of newborns with NAS. The Kids' Inpatient Database (KID) was used to identify newborns with NAS by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. The Nationwide Inpatient Sample (NIS) was used to identify mothers using diagnosis related groups for vaginal and cesarean deliveries. Clinical conditions were identified using ICD-9-CM diagnosis codes. NAS and maternal opiate use were described as an annual frequency per 1000 hospital births. Missing hospital charges (<5% of cases) were estimated using multiple imputation. Trends in health care utilization outcomes over time were evaluated using variance-weighted regression. All hospital charges were adjusted for inflation to 2009 US dollars. MAIN OUTCOME MEASURES: Incidence of NAS and maternal opiate use, and related hospital charges. RESULTS: The separate years (2000, 2003, 2006, and 2009) of national discharge data included 2920 to 9674 unweighted discharges with NAS and 987 to 4563 unweighted discharges for mothers diagnosed with antepartum opiate use, within data sets including 784,191 to 1.1 million discharges for children (KID) and 816,554 to 879,910 discharges for all ages of delivering mothers (NIS). Between 2000 and 2009, the incidence of NAS among newborns increased from 1.20 (95% CI, 1.04-1.37) to 3.39 (95% CI, 3.12-3.67) per 1000 hospital births per year (P for trend < .001). Antepartum maternal opiate use also increased from 1.19 (95% CI, 1.01-1.35) to 5.63 (95% CI, 4.40-6.71) per 1000 hospital births per year (P for trend < .001). In 2009, newborns with NAS were more likely than all other hospital births to have low birthweight (19.1%; SE, 0.5%; vs 7.0%; SE, 0.2%), have respiratory complications (30.9%; SE, 0.7%; vs 8.9%; SE, 0.1%), and be covered by Medicaid (78.1%; SE, 0.8%; vs 45.5%; SE, 0.7%; all P < .001). Mean hospital charges for discharges with NAS increased from $39,400 (95% CI, $33,400-$45,400) in 2000 to $53,400 (95% CI, $49,000-$57,700) in 2009 (P for trend < .001). By 2009, 77.6% of charges for NAS were attributed to state Medicaid programs. CONCLUSION: Between 2000 and 2009, a substantial increase in the incidence of NAS and maternal opiate use in the United States was observed, as well as hospital charges related to NAS.

Increased SOD1 association with chromatin, DNA damage, p53 activation, and apoptosis in a cellular model of SOD1-linked ALS.

Mutations in the gene encoding cytosolic Cu,Zn-superoxide dismutase (SOD1) have been linked to familial amyotrophic lateral sclerosis (FALS). However the molecular mechanisms of motor neuron death are multi-factorial and remain unclear. Here we examined DNA damage, p53 activity and apoptosis in SH-SY5Y human neuroblastoma cells transfected to achieve low-level expression of either wild-type or mutant Gly(93)-->Ala (G93A) SOD1, typical of FALS. DNA damage was investigated by evaluating the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and DNA strand breaks. Significantly higher levels of DNA damage, increased p53 activity, and a greater percentage of apoptotic cells were observed in SH-SY5Y cells transfected with G93A SOD1 when compared to cells overexpressing wild-type SOD1 and untransfected cells. Western blot, FACS, and confocal microscopy analysis demonstrated that G93A SOD1 is present in the nucleus in association with DNA. Nuclear G93A SOD1 has identical superoxide dismutase activity but displays increased peroxidase activity when compared to wild-type SOD1. These results indicate that the G93A mutant SOD1 association with DNA might induce DNA damage and trigger the apoptotic response by activating p53. This toxic activity of mutant SOD1 in the nucleus may play an important role in the complex mechanisms associated with motor neuron death observed in ALS pathogenesis.

Clinical course of symptomatic spontaneous pneumothorax in term and late preterm newborns: report from a large cohort.

The purpose of this observational study was to characterize the clinical course of newborn infants with spontaneous pneumothorax and to identify those infants who eventually required further interventions. We performed a retrospective review of newborns with symptomatic spontaneous pneumothorax, born between January 2002 and December 2007. Seventy-six infants ≥36 weeks' gestation were identified with symptomatic spontaneous pneumothorax. Twenty-two (29%) of the 76 infants with spontaneous pneumothorax required either thoracentesis or/and thoracostomy drainage, and 54 (71%) were managed without such intervention. In all, 18 (24%) infants received mechanical ventilation and 12 (16%) infants developed persistent pulmonary hypertension (PPHN) during the course of illness. Ten of the 22 infants requiring thoracentesis and/or thoracostomy for progressively worsening respiratory distress developed PPHN. Seven of these 10 infants with PPHN received inhaled nitric oxide, and four infants subsequently required extracorporeal membrane oxygenation. In contrast, the majority of the infants (50 of 54, 93%) not requiring thoracentesis or/and thoracostomy could be managed simply with supplemental oxygen or close observation. Progressively worsening respiratory distress prompting intervention in infants with spontaneous pneumothorax may indicate presence of PPHN that needs prompt recognition and referral to tertiary-level neonatal units for escalating respiratory support.

A validated search assessment tool: assessing practice-based learning and improvement in a residency program.

OBJECTIVE: The objective of this study was to validate an assessment instrument for MEDLINE search strategies at an academic medical center. METHOD: Two approaches were used to investigate if the search assessment tool could capture performance differences in search strategy construction. First, data from an evaluation of MEDLINE searches from a pediatric resident's longitudinal assessment were investigated. Second, a cross-section of search strategies from residents in one incoming class was compared with strategies of residents graduating a year later. MEDLINE search strategies formulated by faculty who had been identified as having search expertise were used as a gold standard comparison. Participants were presented with a clinical scenario and asked to identify the search question and conduct a MEDLINE search. Two librarians rated the blinded search strategies. RESULTS: Search strategy scores were significantly higher for residents who received training than the comparison group with no training. There was no significant difference in search strategy scores between senior residents who received training and faculty experts. CONCLUSION: The results provide evidence for the validity of the instrument to evaluate MEDLINE search strategies. This assessment tool can measure improvements in information-seeking skills and provide data to fulfill Accreditation Council for Graduate Medical Education competencies.

The effect of ibuprofen and caffeine prophylaxis on retinopathy of prematurity.

PURPOSE: To determine whether prophylactic caffeine and ibuprofen, which have been shown to have vascular endothelial growth factor-modulating properties in other contexts, have a detectable effect on the incidence of severe retinopathy of prematurity (ROP) when administered in extremely low birth weight infants during the first 48 hours of life. METHODS: In this retrospective cohort study, the incidence and severity of ROP with respect to total exposure to caffeine and ibuprofen were assessed. The effect of oxygen exposure at 28 days' postnatal age (PNA) and 36 weeks' corrected gestational age (GA) was also studied. RESULTS: A total of 109 infants were included; of these, complete data were available for 93 infants (87%), of whom 18 (19%) had severe ROP (ETROP type 1, or stage 3), and 75 (81%) had mild-to-moderate ROP at final diagnosis. Infants with severe ROP had lower GA (P = 0.0006). Total caffeine and ibuprofen exposure did not vary with severity of ROP (P = 0.86 caffeine; P = 0.57 ibuprofen). Presence of oxygen at 28 days' PNA (P = 0.01) or 36 weeks' corrected GA varied significantly with ROP severity (P = 0.0005). CONCLUSIONS: A relationship between prophylactic caffeine and ibuprofen exposure and severity of ROP could not be detected in our study cohort. Presence of oxygen at 28 days' PNA or 36 weeks' corrected GA was associated with ROP severity.

Transient neonatal myasthenia gravis: refining risk estimate for infants born to women with myasthenia gravis.

OBJECTIVE: Transient neonatal myasthenia gravis (TNMG) can render a neonate vulnerable to catastrophic respiratory depression. Our aim was to describe the clinical manifestations of TNMG, and to determine when the myasthenic signs become apparent in TNMG. METHODS: We reviewed our own experience of infants who underwent routine inpatient monitoring for TNMG and combined our local data with observations from previous studies. RESULTS: Only three case series (n = 110) reported both the type and timing of onset of myasthenic signs. Adding local data (n = 37) yielded 147 infants born to women with MG. Fifteen infants (10%) developed signs of TNMG with onset being 1.5 ± 2.6 days (mean ± 3SD) after birth. Feeding difficulties and low tone were the commonest presenting signs, and only 1 of the 147 infants needed intubation for hypoventilation. CONCLUSIONS: TNMG signs were mostly not life-threatening. We suggest only 4 days of routine postnatal observation for infants born to women with MG.

Implantable and Degradable Thermoplastic Elastomer.

Biodegradable and implantable materials having elastomeric properties are highly desirable for many biomedical applications. Here, we report that poly(lactide)-co-poly(ß-methyl-δ-valerolactone)-co-poly(lactide) (PLA-PßMδVL-PLA), a thermoplastic triblock poly(α-ester), has combined favorable properties of elasticity, biodegradability, and biocompatibility. This material exhibits excellent elastomeric properties in both dry and aqueous environments. The elongation at break is approximately 1000%, and stretched specimens completely recover to their original shape after force is removed. The material is degradable both in vitro and in vivo; it degrades more slowly than poly(glycerol sebacate) and more rapidly than poly(caprolactone) in vivo. Both the polymer and its degradation product show high cytocompatibility in vitro. The histopathological analysis of PLA-PßMδVL-PLA specimens implanted in the gluteal muscle of rats for 1, 4, and 8 weeks revealed similar tissue responses as compared with poly(glycerol sebacate) and poly(caprolactone) controls, two widely accepted implantable polymers, suggesting that PLA-PßMδVL-PLA can potentially be used as an implantable material with favorable in vivo biocompatibility. The thermoplastic nature allows this elastomer to be readily processed, as demonstrated by the facile fabrication of the substrates with topographical cues to enhance muscle cell alignment. These properties collectively make this polymer potentially highly valuable for applications such as medical devices and tissue engineering scaffolds.