Analysis of Maternal and Congenital Syphilis Rates at a New Jersey University Hospital.

Syphilis and congenital syphilis (CS) cases have been rising in the U.S. and internationally since the 2000s. Social factors have been shown to increase the risk of CS transmission. The COVID-19 pandemic may have contributed to increased syphilis transmission. We aimed to quantify the rise in congenital syphilis (CS) rates at a large urban hospital and the impact of the COVID-19 pandemic on CS rates. We completed a retrospective chart review of 61 pregnant women with a positive test or previous diagnosis of syphilis at an urban academic hospital between 1 January 2016 and 1 June 2022. Maternal syphilis and CS rates increased over the 5 years (p < 0.001), particularly pre- and post-COVID-19 (p < 0.001). Of the mothers studied, 34.6% received adequate prenatal care, 62.7% received adequate screening, and 81.3% received adequate treatment. Stillbirth was noted in 6.6% of pregnancies. Of liveborn infants, 97.6% received appropriate treatment, and 45.1% received adequate follow-up. CS development was significantly associated with homelessness (p = 0.028) and past opioid use (p = 0.031). We concluded that maternal syphilis and CS rates have increased at our hospital, particularly during the COVID-19 pandemic. Access to prenatal care and timely maternal treatment are target areas for improvement.

Hyperoxia-Induced miR-195 Causes Bronchopulmonary Dysplasia in Neonatal Mice.

Background: Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the pathogenesis of BPD and provide a potential therapeutic target. Methods: This study was conducted utilizing a postnatal animal model of experimental hyperoxia-induced murine BPD to investigate the expression and function of miR-195 as well as its molecular signaling targets within developing mouse lung tissue. Results: miR-195 expression levels increased in response to hyperoxia in male and female lungs, with the most significant elevation occurring in 40% O2 (mild) and 60% O2 (moderate) BPD. The inhibition of miR-195 improved pulmonary morphology in the hyperoxia-induced BPD model in male and female mice with females showing more resistance to injury and better recovery of alveolar chord length, septal thickness, and radial alveolar count. Additionally, we reveal miR-195-dependent signaling pathways involved in BPD and identify PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) as a novel specific target protein of miR-195. Conclusions: Our data demonstrate that high levels of miR-195 in neonatal lungs cause the exacerbation of hyperoxia-induced experimental BPD while its inhibition results in amelioration. This finding suggests a therapeutic potential of miR-195 inhibition in preventing BPD.

From Diagnosis to Precision Surgery: The Transformative Role of Artificial Intelligence in Urologic Imaging.

The multidisciplinary nature of artificial intelligence (AI) has allowed for rapid growth of its application in medical imaging. Artificial intelligence algorithms can augment various imaging modalities, such as X-rays, CT, and MRI, to improve image quality and generate high-resolution three-dimensional images. AI reconstruction of three-dimensional models of patient anatomy from CT or MRI scans can better enable urologists to visualize structures and accurately plan surgical approaches. AI can also be optimized to create virtual reality simulations of surgical procedures based on patient-specific data, giving urologists more hands-on experience and preparation. Recent development of artificial intelligence modalities, such as TeraRecon and Ceevra, offer rapid and efficient medical imaging analyses aimed at enhancing the provision of urologic care, notably for intraoperative guidance during robot-assisted radical prostatectomy (RARP) and partial nephrectomy.

Impact of severity and age with variable definitions of bronchopulmonary dysplasia on neurodevelopmental outcomes.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with neurodevelopmental impairment (NDI). METHODS: To compare the ability of NICHD 2001 and Jensen 2019 definitions of BPD and respiratory support at 40 weeks postmenstrual age (PMA) to predict NDI, a retrospective study (1/2010-12/2020) was conducted in infants with gestational age <32 weeks and birth weight <1500 g. The primary outcome measure was NDI at 18-24 months corrected age. RESULTS: Of 1119 infants, 227 (20.7%) met the inclusion criteria and had adequate follow-up data. Multivariate regression analysis showed that the NICHD 2001 definition was not predictive of NDI. Infants with Grade 2 or 3 BPD (Jensen 2019) had 4.75 (95% CI: 1.282-17.563) times greater odds of having NDI than infants without BPD. Infants requiring respiratory support at 40 weeks PMA had 4.95 (95% CI: 1.490-16.47) times greater odds of having NDI. Receiver operating characteristic curves demonstrated that the 2 definitions of BPD and the need for respiratory support at 40 weeks PMA were similar in their ability to predict NDI. CONCLUSION: There is no significant difference in the ability of the NICHD 2001 and Jensen 2019 BPD definitions, as well as the need for respiratory support at 40 weeks, for predicting NDI. IMPACT STATEMENT: Current bronchopulmonary dysplasia (BPD) definitions may not effectively predict neurodevelopmental impairment (NDI) in preterm infants. Grades 2/3 BPD (Jensen 2019 criteria) significantly associate with NDI. Infants requiring respiratory support at 40 weeks post-menstrual age (PMA) have 5 times higher odds of NDI than those on room air at 40 weeks PMA. The NICHD 2001, Jensen 2019 definitions, and the requirement for respiratory support at 40 weeks PMA, do not differ in their ability to predict NDI. Future studies should include multiple centers, with level III-IV NICUs, catering to socioeconomic, culturally, and racially diverse populations.

Timing and risk factors associated with acute kidney injury in infants with necrotizing enterocolitis.

OBJECTIVE: To evaluate the prevalence, onset, risk factors, and mortality associated with acute kidney injury (AKI) in infants with necrotizing enterocolitis (NEC). DESIGN/METHODS: Retrospective study at 2 centers in infants with NEC, with/without AKI. AKI assessed by serum creatinine and urine output. Statistical tests used included t, Mann-Whitney U, Chi-square, and Fisher Exact tests. RESULTS: Among 80 eligible infants with NEC, 56 (70%) had AKI. Median onset of NEC was day 15, with median AKI onset two days (IQR, -5.75 to 0) prior to NEC onset. Vasopressors were significantly more likely to be used in infants with NEC and AKI (p = 0.009). Increased mortality (p = 0.01) was noted in infants with NEC and AKI. CONCLUSIONS: The onset of AKI mostly precedes NEC onset, with moderate to severe AKI more prevalent than the milder form in infants with NEC. These infants are significantly more likely to be hemodynamically unstable and have increased mortality.

Safety of bubble nasal intermittent positive pressure ventilation (NIPPV) versus bubble nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress.

OBJECTIVE: Nasal Intermittent Positive Pressure Ventilation (NIPPV) is an effective therapy for infants in respiratory distress. We here report the safety of a novel, low-cost, non-electric bubble NIPPV device in comparison with bubble NCPAP. STUDY DESIGN: At Paramitha Children's Hospital (Hyderabad, India), preterm (n = 60) neonates with moderate respiratory distress were pragmatically allocated to bubble NCPAP (5-8 cm H2O) or bubble NIPPV (Phigh 8-12 cm H2O/Plow 5-8 cm H2O) based on staff and equipment availability. Primary outcomes to assess safety included clinically relevant pneumothorax, nasal septal necrosis, or abdominal distention. RESULTS: One patient in each arm developed minor nasal septal injury (grade 3 on NCPAP, grade 2 on NIPPV); no patients in either arm developed a clinically significant pneumothorax or abdominal distention. CONCLUSION: The similar rates of nasal septal injury, pneumothorax and abdominal distention suggest that bubble NIPPV has a similar safety profile as bubble NCPAP for preterm infants in respiratory distress.

Iron Deficiency Prior to Discharge in Very Low Birth Weight Infants: Screening with Reticulocyte Hemoglobin Content.

OBJECTIVE: This study aimed to assess the iron status prior to discharge in very low birth weight (VLBW) infants utilizing reticulocyte hemoglobin content (CHr) and evaluate the impact of delayed cord clamping (DCC) on iron status. STUDY DESIGN: This is a retrospective analysis of VLBW infants from two tertiary level of care Neonatal Intensive Care Units. The primary outcome was the proportion of VLBW infants with low CHr (<29 pg) prior to discharge. Hematologic parameters were also compared between infants who received or did not receive DCC. Infants with a positive newborn screen for hemoglobin Bart's were excluded. RESULTS: Among the 315 infants included, 99 infants (31.4%) had low CHr prior to discharge. The median (interquartile range) CHr prior to discharge was 30.8 pg (28.4-39 pg). DCC was performed in 46.7% of infants. Hemoglobin at birth, discharge, and CHr prior to discharge were higher and the need for blood transfusion and the number of infants with low CHr prior to discharge were lower in the DCC group. CONCLUSION: Approximately 31.4% of VLBW infants had low CHr near the time of discharge suggesting they were iron deficient. DCC improved hematological parameters prior to discharge in VLBW infants. CHr content can be used to guide iron supplementation in VLBW infants to potentially improve their iron status and long-term neurocognitive outcomes. KEY POINTS: · DCC was associated with an improved hemoglobin and iron status at discharge in VLBW infants.. · CHr is an early and reliable marker for iron deficiency.. · Approximately one in three VLBW infants can be iron deficient at the time of discharge..

Pulmonary phenotypes of bronchopulmonary dysplasia in the preterm infant.

Bronchopulmonary dysplasia (BPD) remains the most common complication of premature birth, imposing a significant and potentially life-long burden on patients and their families. Despite advances in our understanding of the mechanisms that contribute to patterns of lung injury and dysfunctional repair, current therapeutic strategies remain non-specific with limited success. Contemporary definitions of BPD continue to rely on clinician prescribed respiratory support requirements at specific time points. While these criteria may be helpful in broadly identifying infants at higher risk of adverse outcomes, they do not offer any precise information regarding the degree to which each compartment of the lung is affected. In this review we will outline the different pulmonary phenotypes of BPD and discuss important features in the pathogenesis, clinical presentation, and management of these frequently overlapping scenarios.

Invasive and non-invasive ventilatory strategies for early and evolving bronchopulmonary dysplasia.

In the age of surfactant and antenatal steroids, neonatal care has improved outcomes of preterm infants dramatically. Since the early 2000's neonatologists have strived to decrease bronchopulmonary dysplasia (BPD) by decreasing ventilator-associated lung injury and utilizing many novel modes of non-invasive respiratory support. After the initial success with nasal continuous positive airway pressure, it was established that discontinuing invasive ventilation early in favor of non-invasive respiratory support is the most effective way to reduce the incidence of BPD. In this review, we discuss the management of the preterm lung from the time of delivery, through the phases of respiratory distress syndrome (early BPD) and then evolving BPD. The goal remains to optimize respiratory support of the preterm lung while minimizing ventilator-associated lung injury and oxygen toxicity. A multidisciplinary approach involving the medical team and family is quintessential in reaching this goal and involves adequate respiratory support, optimizing nutrition and fluid balance as well as preventing infections.

Incidence of Neonatal Seizures in China Based on Electroencephalogram Monitoring in Neonatal Neurocritical Care Units.

Importance: Neonatal seizures pose a significant challenge in critical care, and continuous video electroencephalography (cEEG) monitoring holds promise for early detection of seizures. However, large-scale data on the incidence of neonatal seizures and monitoring systems in China are lacking. Objectives: To determine the incidence of neonatal seizures in infants with high risk in China. Design, Setting, and Participants: A large, cross-sectional multicenter study was conducted from January 2017 to December 2018 in the neonatal intensive care units (NICUs) of 7 tertiary medical centers in China. Neonates with high risk were included, and cEEG monitoring was conducted. Data were collected between January 1, 2017, and January 31, 2020. The data were analyzed between January 2021 and January 2022. Main Outcomes and Measures: The incidence of neonatal seizures, categorized by etiology, and seizure burden. Results: A total of 20 310 neonates with high risk were included (10 495 [51.7%] male; mean [SD] postmenstrual age, 37.7 [3.7] weeks), and seizures were observed in 3423 infants (16.9%). The highest proportion of seizures was attributed to acute neonatal encephalopathy (1448 [42.3%]). The incidence of seizures decreased with postmenstrual age and birth weight, with the highest occurrence observed in neonates with postmenstrual age of less than 28 weeks (237 of 879 [27.0%]) or birth weight of less than 1.0 kg (269 of 914 [29.4%]). Preterm infants had a higher proportion of moderate and severe seizure burdens compared with full-term infants (moderate severity: 248 of 1199 [20.7%] vs 454 of 2224 [20.4%]), but no significant differences were observed in etiology. Seizure burden was highest with genetic syndromes (49 of 188 [26.1%]), central nervous system malformations (33 of 127 [26.0%]), and inborn errors of metabolism (27 of 113 [23.9%]). During hospitalization, 7.8% of neonates with seizures died (267 neonates), with 81.3% of these cases having a moderate or severe seizure burden (217 neonates). Mortality was generally higher in preterm vs full-term infants (98 of 1199 [8.2%] vs 169 of 2224 [7.6%]) and increased with the severity of seizure burden (217 of 267 neonates with moderate or severe burden [81.3%]). Conclusions and Relevance: This cross-sectional study of neonatal seizures underscores the substantial burden seizures pose to high-risk infants with brain injury in China, particularly those who are born prematurely or who have congenital conditions.

RDS-NExT workshop: consensus statements for the use of surfactant in preterm neonates with RDS.

OBJECTIVE: To provide the best clinical practice guidance for surfactant use in preterm neonates with respiratory distress syndrome (RDS). The RDS-Neonatal Expert Taskforce (RDS-NExT) initiative was intended to add to existing evidence and clinical guidelines, where evidence is lacking, with input from an expert panel. STUDY DESIGN: An expert panel of healthcare providers specializing in neonatal intensive care was convened and administered a survey questionnaire, followed by 3 virtual workshops. A modified Delphi method was used to obtain consensus around topics in surfactant use in neonatal RDS. RESULT: Statements focused on establishing RDS diagnosis and indicators for surfactant administration, surfactant administration methods and techniques, and other considerations. After discussion and voting, consensus was achieved on 20 statements. CONCLUSION: These consensus statements provide practical guidance for surfactant administration in preterm neonates with RDS, with a goal to contribute to improving the care of neonates and providing a stimulus for further investigation to bridge existing knowledge gaps.

Mapping N- to C-terminal allosteric coupling through disruption of a putative CD74 activation site in D-dopachrome tautomerase.

The macrophage migration inhibitory factor (MIF) protein family consists of MIF and D-dopachrome tautomerase (also known as MIF-2). These homologs share 34% sequence identity while maintaining nearly indistinguishable tertiary and quaternary structure, which is likely a major contributor to their overlapping functions, including the binding and activation of the cluster of differentiation 74 (CD74) receptor to mediate inflammation. Previously, we investigated a novel allosteric site, Tyr99, that modulated N-terminal catalytic activity in MIF through a "pathway" of dynamically coupled residues. In a comparative study, we revealed an analogous allosteric pathway in MIF-2 despite its unique primary sequence. Disruptions of the MIF and MIF-2 N termini also diminished CD74 activation at the C terminus, though the receptor activation site is not fully defined in MIF-2. In this study, we use site-directed mutagenesis, NMR spectroscopy, molecular simulations, in vitro and in vivo biochemistry to explore the putative CD74 activation region of MIF-2 based on homology to MIF. We also confirm its reciprocal structural coupling to the MIF-2 allosteric site and N-terminal enzymatic site. Thus, we provide further insight into the CD74 activation site of MIF-2 and its allosteric coupling for immunoregulation.

Correlation of Polymorphonuclear Cell Burden and Microbial Growth to the Inflammatory Cytokines in Tracheal Aspirates from Ventilated Preterm Infants.

OBJECTIVE: The significance of the presence of microorganisms and polymorphonuclear cells in the tracheal aspirates (TAs) of ventilated preterm infants is not well known. Our aim was to correlate information about the presence of polymorphonuclear cells with microbial growth and the cytokine milieu in the TAs of infants who have been intubated for >7 days. STUDY DESIGN: TAs were collected from infants who had been intubated for 7 days or longer. Respiratory cultures were performed, and infants were stratified based on the presence and abundance of polymorphonuclear cells and microbial growth. Cytokines were measured in the TAs of each of the respective groups. RESULTS: In the 19 infants whose TAs were collected, the presence of at least moderate WBC with presence of microbial growth was positively associated with the presence of interleukin (IL)-10, IL-1ß, IL-8, and tumor necrosis factor (TNF)-α. The presence of at least moderate WBC, with or without microbial growth, was correlated positively with the presence of IL-8 and TNF-α. CONCLUSION: There are higher levels of proinflammatory cytokines (especially, IL-10, IL-1ß, and TNF-α) in TAs with higher cell counts and presence of microbial growth. The findings suggest that the presence of microbial growth correlated with inflammatory burden and warrant a larger study to see if treatment of microbial growth can ameliorate the inflammatory burden. KEY POINTS: · Concomitant evaluation of inflammatory cells, microbial growth, and cytokines in tracheal aspirates.. · Moderate TA WBC with presence of microbial growth associated with IL-10, IL-1ß, IL-8, and TNF-α.. · Moderate TA WBC, with/without microbial growth, correlated with the presence of IL-8 and TNF-α.. · Higher levels of IL-10, IL-1ß, and TNF-α correlated with higher TA cell counts and microbial growth..

2,5-Pyridinedicarboxylic acid is a bioactive and highly selective inhibitor of D-dopachrome tautomerase.

Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (D-DT) are two pleotropic cytokines, which are coexpressed in various cell types to activate the cell surface receptor CD74. Via the MIF/CD74 and D-DT/CD74 axes, the two proteins exhibit either beneficial or deleterious effect on human diseases. In this study, we report the identification of 2,5-pyridinedicarboxylic acid (a.k.a. 1) that effectively blocks the D-DT-induced activation of CD74 and demonstrates an impressive 79-fold selectivity for D-DT over MIF. Crystallographic characterization of D-DT-1 elucidates the binding features of 1 and reveals previously unrecognized differences between the MIF and D-DT active sites that explain the ligand's functional selectivity. The commercial availability, low cost, and high selectivity make 1 the ideal tool for studying the pathophysiological functionality of D-DT in disease models. At the same time, our comprehensive biochemical, computational, and crystallographic analyses serve as a guide for generating highly potent and selective D-DT inhibitors.

Respiratory management in the premature neonate.

INTRODUCTION: Advances in neonatal care have made possible the increased survival of extremely preterm infants. Even though there is widespread recognition of the harmful effects of mechanical ventilation on the developing lung, its use has become imperative in the management of micro-/nano-preemies. There is an increased emphasis on the use of less-invasive approaches such as minimally invasive surfactant therapy and non-invasive ventilation that have been proven to result in improved outcomes. AREAS COVERED: Here, we review the evidence-based practices surrounding the respiratory management of extremely preterm infants including delivery room interventions, invasive and non-invasive ventilation approaches, and specific ventilator strategies in respiratory distress syndrome and bronchopulmonary dysplasia. Adjuvant relevant respiratory pharmacotherapies used in preterm neonates are also discussed. EXPERT OPINION: Early use of non-invasive ventilation and use of less invasive surfactant administration are key strategies in the management of respiratory distress syndrome in preterm infants. Ventilator management in bronchopulmonary dysplasia must be tailored according to the individual phenotype. There is strong evidence to start caffeine early to improve respiratory outcomes, but evidence is lacking on the use of other pharmacological agents in preterm neonates, and an individualized approach has to be considered for their use.

Nasal intermittent positive pressure ventilation as a rescue therapy after nasal continuous positive airway pressure failure in infants with respiratory distress syndrome.

OBJECTIVE: Evaluate whether nasal intermittent positive-pressure ventilation (NIPPV) as rescue therapy after initial nasal continuous positive airway (NCPAP) failure reduces need for invasive mechanical ventilation (IMV) in infants with respiratory distress syndrome (RDS). DESIGN: Retrospective cohort involving 156 preterm infants who failed initial NCPAP and were then submitted to NIPPV rescue therapy and classified into NIPPV success or failure, according to need for IMV. RESULT: Of all infants included, 85 (54.5%) were successfully rescued with NIPPV while 71 (45.5%) failed. The NIPPV success group had significantly lower rates of bronchopulmonary dysplasia, peri/intraventricular hemorrhage, patent ductus arteriosus and greater survival without morbidities (all p ≤ 0.01). Infants who failed NIPPV had earlier initial NCPAP failure (p = 0.09). In final logistic regression model, birthweight ≤1000 g and need for surfactant remained significant factors for NIPPV failure. CONCLUSION: NIPPV rescue therapy reduced the need for IMV in infants that failed NCPAP and was associated with better outcomes.

Reticulocyte Count: The Forgotten Factor in Transfusion Decisions for Extremely Low Birth Weight Infants.

OBJECTIVE: Extremely low birth weight (ELBW) infants often receive transfusions of packed red blood cells (PRBCs). Long-term outcomes of infants treated with liberal versus restricted transfusion criteria have been evaluated with conflicting results. Clinicians incorporate a reticulocyte count (RC) in their transfusion decisions. There is a lack of information on reference ranges for RCs in growing ELBW infants and whether infant's chronologic age or corrected gestational age (GA) generates a specific trend in the RCs. Our aim was to evaluate the levels of RCs obtained from ELBW infants over the course of the initial hospitalization. STUDY DESIGN: A retrospective chart review of ELBW infants treated in the neonatal intensive care unit (NICU) and had RCs performed. We analyzed the RCs to observe trends based on the chronologic age and corrected GA. RESULTS: A total of 738 RCs were analyzed. A positive trend in RCs that reached a peak at 32 to 34 weeks' corrected GA and then experienced a downward trend was observed. CONCLUSION: Our report examines a very common hematologic test that is theoretically helpful but is in need of guidelines concerning the appropriate frequency of testing and its utility in making transfusion decisions in ELBW infants. KEY POINTS: · RCs should help in making transfusion decisions for ELBW infants.. · No current reference ranges for RC in this population.. · No current reference ranges for RC based on GA and postnatal age..