On traveling wave solutions with stability and phase plane analysis for the modified Benjamin-Bona-Mahony equation.

The modified Benjamin-Bona-Mahony (mBBM) model is utilized in the optical illusion field to describe the propagation of long waves in a nonlinear dispersive medium during a visual illusion (Khater 2021). This article investigates the mBBM equation through the utilization of the rational [Formula: see text]-expansion technique to derive new analytical wave solutions. The analytical solutions we have obtained comprise hyperbolic, trigonometric, and rational functions. Some of these exact solutions closely align with previously published results in specific cases, affirming the validity of our other solutions. To provide insights into diverse wave propagation characteristics, we have conducted an in-depth analysis of these solutions using 2D, 3D, and density plots. We also investigated the effects of various parameters on the characteristics of the obtained wave solutions of the model. Moreover, we employed the techniques of linear stability to perform stability analysis of the considered model. Additionally, we have explored the stability of the associated dynamical system through the application of phase plane theory. This study also demonstrates the efficacy and capabilities of the rational [Formula: see text]-expansion approach in analyzing and extracting soliton solutions from nonlinear partial differential equations.

Comparison of efficacy between beractant and poractant alfa in respiratory distress syndrome among preterm infants (28-33+6 weeks gestational age) using the less invasive surfactant administration (LISA) technique: A randomized controlled trial.

OBJECTIVE: Exogenous surfactant therapy is vital in managing respiratory distress syndrome (RDS) in preterm infants, with less invasive surfactant administration (LISA) gaining popularity. This study aimed to assess the efficacy and short-term outcomes of LISA using beractant and poractant alfa. STUDY DESIGN: In a randomized controlled trial, we enrolled preterm infants (28-33+6 weeks) with RDS requiring surfactant. LISA was employed, with beractant at 100 mg/kg or poractant-alfa at 200 mg/kg. Primary outcome was the need for intubation within 72 hours. RESULTS: Among 120 infants, 3.3% in both groups required intubation within 72 hours (p value 1.00, 95% CI 0.14-6.86). No significant differences in secondary outcomes were noted. However, beractant was significantly more economical than poractant-alfa, with a significantly lower surfactant cost and total care cost for infant hospital stays. CONCLUSION: Beractant and poractant-alfa exhibit similar efficacy in LISA for preterm infants with RDS. Economic considerations, especially in LMICs, favour beractant. CLINICAL TRIAL REGISTATION: (CTRI/2023/03/050375).

Squamous cell carcinoma of breast metastasising to upper lip.

Breast cancer is a heterogeneous set of carcinomas comprising a subgroup of invasive ductal carcinomas and numerous infrequent subtypes. Primary squamous cell carcinoma (SCC) breast is sporadic, accounting for less than 0.1% of all invasive subtypes. Primary metastases to soft tissues of the oral cavity are incredibly rare, amounting to 0.1% of oral malignancies. Diagnosing metastasis to the oral cavity is an enigma to clinicians without pathognomonic signs and symptoms. Here, we report a case of SCC breast, who developed metastatic deposits in the left upper lip after a disease-free survival of 1 year. There are no reports of SCC breast metastasising to the oral cavity, and probably, this is the first such case getting reported. The survival of such patients is abysmal, with most cases surviving less than a year post diagnosis. While treating patients with a history of malignancy, a high degree of clinical presentiment is required.

Surgical Management of Oral Cavity Cancer: Experience at a Tertiary Care Centre in Jamshedpur.

Background Cancer of the oral cavity is very common in Eastern India. This is due to the lack of awareness that chewing tobacco causes oral cancer. Because of poor economic condition and lack of access to healthcare, patients in this region often present at an advanced stage of the disease when they become symptomatic. A retrospective study was conducted at Tata Main Hospital, Jamshedpur, India, to know the epidemiology and recurrence of oral cavity cancer in this region. Materials and methods We conducted a retrospective study of oral cavity cancer patients operated at Tata Main Hospital, Jamshedpur, from January 2018 to June 2023. Data were collected from the surgical register, operation theatre notes, case sheets and hospital online data. The following parameters were observed in this study: a) age, b) gender, c) site of cancer, d) histology, e) stage of disease at presentation, f) type of neck dissection, g) margin status on the final histopathology report, h) node positivity, i) presence of perineural invasion or lymphovascular invasion and j) recurrence.  Results A total of 218 patients were operated between January 2018 and June 2023. The most common site for oral cavity cancer was the buccal mucosa with the involvement of the lower alveolus (168 patients, 77.06%), followed by the tongue (27 patients, 12.38%). Two-hundred seventeen patients were diagnosed with squamous cell carcinoma (SCC), and one patient had epithelioid sarcoma on the biopsy report. The most common stage of presentation was stage IVa (180 patients, 82.56%), followed by stage III (16 patients, 7.34%). The most frequent neck dissection performed was modified radical neck dissection (MRND) sacrificing the sternocleidomastoid muscle (SCM) and preserving the internal juglar vein (IJV) and spinal accessory nerve (SAN) (176 patients, 80%). The margin was positive for 10 patients. Node positivity on the final histopathology report grouped according to the clinical stage are as follows: stage I (33.33%), stage II (60%), stage III (75%) and stage IV (86.67%). Similarly, the presence of lymphovascular or perineural invasion on the final histopathology report grouped according to the clinical stage is as follows: stage I (0%), stage II (20%), stage III (25%) and stage IV (55.55 %). Fifteen patients lost to follow-up. Recurrence was noted in 11 patients (5.04%). Patients presenting with stages I and II had no recurrence, whereas three out of 16 patients in stage III (1.1%) and eight out of 180 patients in stage IV (4.44%) had recurrence. Conclusion SCC is the most common type of oral cavity cancer in Eastern India. It is strongly related to tobacco chewing habit. Since most of the patients in this part of the country present with an advanced stage of the disease, awareness regarding cessation of tobacco use and screening can be beneficial to the general population.

Carriage and within-host diversity of mcr-1.1-harbouring Escherichia coli from pregnant mothers: inter- and intra-mother transmission dynamics of mcr-1.1.

Exchange of antimicrobial resistance genes via mobile genetic elements occur in the gut which can be transferred from mother to neonate during birth. This study is the first to analyse transmissible colistin resistance gene, mcr, in pregnant mothers and neonates. Samples were collected from pregnant mothers (rectal) and septicaemic neonates (rectal and blood) and analysed for the presence of mcr, its transmissibility, genome diversity, and exchange of mcr between isolates within an individual and across different individuals (not necessarily mother-baby pairs). mcr-1.1 was detected in rectal samples of pregnant mothers (n = 10, 0.9%), but not in neonates. All mcr-positive mothers gave birth to healthy neonates from whom rectal specimen were not collected. Hence, the transmission of mcr between these mother-neonate pairs could not be studied. mcr-1.1 was noted only in Escherichia coli (phylogroup A & B1), and carried few resistance and virulence genes. Isolates belonged to diverse sequence types (n = 11) with two novel STs (ST12452, ST12455). mcr-1.1 was borne on conjugative IncHI2 bracketed between ISApl1 on Tn6630, and the plasmids exhibited similarities in sequences across the study isolates. Phylogenetic comparison showed that study isolates were related to mcr-positive isolates of animal origin from Southeast Asian countries. Spread of mcr-1.1 within this study occurred either via similar mcr-positive clones or similar mcr-bearing plasmids in mothers. Though this study could not build evidence for mother-baby transmission but the presence of such genes in the maternal specimen may enhance the chances of transmission to neonates.

Experience of less invasive surfactant administration with a 5F infant feeding tube in a tertiary center of low- and middle-income countries.

BACKGROUND: Less invasive surfactant administration (LISA) results in less need for mechanical ventilation and a reduction in death, bronchopulmonary dysplasia, and intraventricular hemorrhage as outcomes. This study aimed to evaluate the efficacy and short-term outcomes of surfactant administration by the LISA method using an 5F infant feeding tube in preterm infants. METHODS: During the period from May, 2019 to August, 2022, we carried out a prospective observational study that included all premature infants with respiratory distress syndrome who were admitted to our neonatal intensive care unit. The study involved collecting and analyzing data on the procedural efficacy of LISA, vital parameters, and short-term outcomes. RESULTS: Our study included a total of 110 infants with an average gestational age of 30.9 ± 1.9 weeks and a mean birthweight of 1347.5 ± 354.1 g. Of these infants, two required intubation during the LISA procedure, whereas 11 infants required intubation within 72 h after LISA. Infants with a higher pre-surfactant fraction of inspired oxygen (Fi O2 ) requirement, an elevated Score for Neonatal Acute Physiology with Perinatal Extension (SNAPPE), and the presence of sepsis were associated with the need for intubation within the first 72 h of life. Thirty-one infants also experienced a drop in saturation of peripheral oxygen (SpO2 ) below 80% for more than 1 min. CONCLUSIONS: Less invasive surfactant administration was feasible and safe to administer via an orotracheally introduced 5F infant feeding tube in non-invasive ventilation to support spontaneously breathing infants between 28+0 and 33+6 weeks of gestation.

Cut umbilical cord milking (C-UCM) as a mode of placental transfusion in non-vigorous preterm neonates: a randomized controlled trial.

Routine practice of delayed cord clamping (DCC) is the standard of care in vigorous neonates. However there is no consensus on the recommended approach to placental transfusion in non-vigorous neonates. In this trial, we tried to examine the effect of cut umbilical cord milking (C-UCM) as compared to early cord clamping (ECC) on hematological and clinical hemodynamic parameters in non-vigorous preterm neonates of 30-35 weeks gestation. The primary outcome assessed was venous hematocrit (Hct) at 48 (± 4) hours of postnatal age. The important secondary outcomes assessed were serum ferritin at 6 weeks of age, mean blood pressure in the initial transitional phase along with important neonatal morbidities and potential complications. In this single centre randomized controlled trial, 134 non vigorous neonates of 30-35 weeks gestation were allocated in a 1:1 ratio to either C-UCM (n = 67) or ECC (n = 67). For statistical analysis, unpaired Student t and Chi square or Fisher's exact test were used. The mean Hct at 48 h was higher in the C-UCM group as compared to the control group, 50.24(4.200) vs 46.16(2.957), p < .0001. Also significantly higher was the mean Hct at 12 h, 6 weeks and mean serum ferritin at 6 weeks of age in the milked group (p < .0001). Mean blood pressure at 1 h and 6 h was also significantly higher in the milked arm. Need for transfusion and inotropes was less in the milked group but not statistically significant. No significant difference in potential complications was observed between the groups.    Conclusion: C-UCM stabilizes initial blood pressure and results in higher hematocrit and improved iron stores. It can be an alternative to DCC in non-vigorous preterm neonates of 30-35 weeks' gestation. Further large multicentric studies are needed to fully establish its efficacy and safety.   Trial registration: CTRI/2021/12/038606; registration date December 14, 2021. What is Known: • DCC is the routinely recommended method of placental transfusion for vigorous neonates but no consensus exist for neonates requiring resuscitation at birth. • C-UCM is easier to perform in non-vigorous neonates but there is paucity of studies in the preterm population. What is New: • C-UCM is effective as well as safe in non-vigorous preterm neonates of 30-35 weeks gestational age. • C-UCM holds promise as an alternative to DCC, especially in resource limited settings and in situations where the later is not feasible.

A Decade-Long Evaluation of Neonatal Septicaemic Escherichia coli: Clonal Lineages, Genomes, and New Delhi Metallo-Beta-Lactamase Variants.

Longitudinal studies of extraintestinal pathogenic Escherichia coli (ExPEC) and epidemic clones of E. coli in association with New Delhi metallo-ß-lactamase (blaNDM) in septicaemic neonates are rare. This study captured the diversity of 80 E. coli isolates collected from septicaemic neonates in terms of antibiotic susceptibility, resistome, phylogroups, sequence types (ST), virulome, plasmids, and integron types over a decade (2009 to 2019). Most of the isolates were multidrug-resistant and, 44% of them were carbapenem-resistant, primarily due to blaNDM. NDM-1 was the sole NDM-variant present in conjugative IncFIA/FIB/FII replicons until 2013, and it was subsequently replaced by other variants, such as NDM-5/-7 found in IncX3/FII. A core genome analysis for blaNDM+ve isolates showed the heterogeneity of the isolates. Fifty percent of the infections were caused by isolates of phylogroups B2 (34%), D (11.25%), and F (4%), whereas the other half were caused by phylogroups A (25%), B1 (11.25%), and C (14%). The isolates were further distributed in approximately 20 clonal complexes (STC), including five epidemic clones (ST131, ST167, ST410, ST648, and ST405). ST167 and ST131 (subclade H30Rx) were dominant, with most of the ST167 being blaNDM+ve and blaCTX-M-15+ve. In contrast, the majority of ST131 isolates were blaNDM-ve but blaCTX-M-15+ve, and they possessed more virulence determinants than did ST167. A single nucleotide polymorphism (SNP)-based comparative genome analysis of epidemic clones ST167 and ST131 in a global context revealed that the study isolates were present in close proximity but were distant from global isolates. The presence of antibiotic-resistant epidemic clones causing sepsis calls for a modification of the recommended antibiotics with which to treat neonatal sepsis. IMPORTANCE Multidrug-resistant and virulent ExPEC causing sepsis in neonates is a challenge to neonatal health. The presence of enzymes, such as carbapenemases (blaNDM) that hydrolyze most ß-lactam antibiotic compounds, result in difficulties when treating neonates. The characterization of ExPECs collected over 10 years showed that 44% of ExPECs were carbapenem-resistant, possessing transmissible blaNDM genes. The isolates belonged to different phylogroups that are considered to be either commensals or virulent. The isolates were distributed in around 20 clonal complexes (STC), including two predominant epidemic clones (ST131 and ST167). ST167 possessed few virulence determinants but was blaNDM+ve. In contrast, ST131 harbored several virulence determinants but was blaNDM-ve. A comparison of the genomes of these epidemic clones in a global context revealed that the study isolates were present in close proximity but were distant from global isolates. The presence of epidemic clones in a vulnerable population with contrasting characteristics and the presence of resistance genes call for strict vigilance.

Clinico-Pathological Factors Determining Recurrence of Phyllodes Tumors of the Breast: The 25-Year Experience at a Tertiary Cancer Centre.

BACKGROUND: Phyllodes tumors (PTs) of the breast are rare fibroepithelial tumors that are generally more prone to recurrence. AIMS AND OBJECTIVES: This study aimed to assess the clinicopathological features, diagnostic modalities, and therapeutic interventions, along with their respective outcomes, to identify the factors associated with a recurrence of PTs of the breast. METHODOLOGY: A retrospective cohort and observational study was conducted, which entailed analyzing the clinicopathological data of patients who were previously diagnosed or presented with PTs of the breast between 1996 and 2021. Data included the total number of patients diagnosed with PTs of the breast and their ages, tumor grade on initial biopsy, tumor location (left or right breast), tumor size, therapeutic interventions carried out (including surgery-either mastectomy or lumpectomy-and adjuvant radiotherapy), final tumor grade, recurrence status, type of recurrence, and time to recurrence. RESULTS: We analyzed data on a total of 87 patients who were pathologically proven to have PTs, and 46 patients (52.87%) were found to have recurrences. All patients were female, with a mean age at diagnosis of 39 years (range 15-70). Patients aged <40 years had the highest incidence of recurrence, with a rate of 54.35% (n = 25/46), followed by patients aged >40 years, with a rate of recurrence of 45.65% (n = 21/46). A total of 55.4% of patients presented with primary PTs and 44.6% had recurrent PTs at presentation. The average time to local recurrence (LR) from the completion of treatment was 13.8 months, whereas for systemic recurrence (SR), it was 15.29 months. Surgery (mastectomy/lumpectomy) was the major determinant for local recurrence (p < 0.05). CONCLUSION: Patients who received adjuvant radiotherapy (RT) had a minimal recurrence of PTs. Patients who were found to have a malignant biopsy on initial diagnosis (triple assessment) had a higher incidence of PTs and were more prone to SR than LR. Surgery was a determining factor in the increased rate of LR, with lumpectomy associated with a higher incidence of LR than mastectomy.

Hypervirulent Klebsiella pneumoniae Causing Neonatal Bloodstream Infections: Emergence of NDM-1-Producing Hypervirulent ST11-K2 and ST15-K54 Strains Possessing pLVPK-Associated Markers.

Klebsiella pneumoniae is a major cause of neonatal sepsis. Hypervirulent Klebsiella pneumoniae (hvKP) that cause invasive infections and/or carbapenem-resistant hvKP (CR-hvKP) limit therapeutic options. Such strains causing neonatal sepsis have rarely been studied. Characterization of neonatal septicemic hvKP/CR-hvKP strains in terms of resistance and virulence was carried out. Antibiotic susceptibility, molecular characterization, evaluation of clonality, in vitro virulence, and transmissibility of carbapenemase genes were evaluated. Whole-genome sequencing (WGS) and mouse lethality assays were performed on strains harboring pLVPK-associated markers. About one-fourth (26%, 28/107) of the studied strains, leading to mortality in 39% (11/28) of the infected neonates, were categorized as hvKP. hvKP-K2 was the prevalent pathotype (64.2%, 18/28), but K54 and K57 were also identified. Most strains were clonally diverse belonging to 12 sequence types, of which ST14 was most common. Majority of hvKPs possessed virulence determinants, strong biofilm-forming, and high serum resistance ability. Nine hvKPs were carbapenem-resistant, harboring blaNDM-1/blaNDM-5 on conjugative plasmids of different replicon types. Two NDM-1-producing high-risk clones, ST11 and ST15, had pLVPK-associated markers (rmpA, rmpA2, iroBCDEN, iucABCDiutA, and peg-344), of which one co-transferred the markers along with blaNDM-1. The 2 strains revealed high inter-genomic resemblance with the other hvKP reference genomes, and were lethal in mouse model. To the best of our knowledge, this study is the first to report on the NDM-1-producing hvKP ST11-K2 and ST15-K54 strains causing fatal neonatal sepsis. The presence of pLVPK-associated markers and blaNDM-1 in high-risk clones, and the co-transmission of these genes via conjugation calls for surveillance of these strains. IMPORTANCE Klebsiella pneumoniae is a leading cause of sepsis in newborns and adults. Among the 2 major pathotypes of K. pneumoniae, classical (cKP) and hypervirulent (hvKP), hvKP causes community-acquired severe fatal invasive infections in even healthy individuals, as it possesses several virulence factors. The lack of comprehensive studies on neonatal septicemic hvKPs prompted this work. Nearly 26% diverse hvKP strains were recovered possessing several resistance and virulence determinants. The majority of them exhibited strong biofilm-forming and high serum resistance ability. Nine of these strains were also carbapenem (last-resort antibiotic)-resistant, of which 2 high-risk clones (ST11-K2 and ST15-K54) harbored markers (pLVPK) noted for their virulence, and were lethal in the mouse model. Genome-level characterization of the high-risk clones showed resemblance with the other hvKP reference genomes. The presence of transmissible carbapenem-resistant gene, blaNDM, along with pLVPK-markers calls for vigilance, as most clinical microbiology laboratories do not test for them.

Comparison of STOPS and SNAPPE-II in Predicting Neonatal Survival at Hospital Discharge: A Prospective, Multicentric, Observational Study.

OBJECTIVE: To compare SNAPPE-II and STOPS admission severity scores in neonates admitted to neonatal intensive care unit (NICU) with a gestational age of ≥ 33 wk. METHODS: In this multicenter, prospective, observational study, the sickness scoring was done on all the neonates at 12 h after admission to the NICUs. The scoring systems were compared by the area under the curve (AUC) on the receiver operating characteristics (ROC) curve. RESULTS: A total of 669 neonates with gestational age ≥ 33 wk (mortality rate: 2.4%), who were admitted to five participating NICUs within 24 h of birth, were included. Both SNAPPE-II and STOPS had the good discriminatory and predictive ability for mortality with AUCs of 0.965 [95% confidence interval (CI): 0.94-0.98] and 0.92 (95% CI: 0.87-0.99), respectively. The STOPS scoring system with a cutoff score ≥ 4 on the ROC curve had 85% accuracy, whereas the SNAPPE-II cutoff score ≥ 33 on the ROC curve had 94% accuracy in predicting mortality. CONCLUSION: In infants with the gestational age of ≥ 33 wk, SNAPPE-II and STOPS showed similar predictive ability, but the STOPS score, being a simpler clinical tool, might be more useful in resource-limited settings.

Comparison of CRIB-II with SNAPPE-II for predicting survival and morbidities before hospital discharge in neonates with gestation ≤ 32 weeks: a prospective multicentric observational study.

Various studies validated and compared Score for Neonatal Acute Physiology with Perinatal extension-II (SNAPPE-II) and Clinical Risk Index for Babies-II (CRIB-II) admission sickness severity scores for predicting survival, but very few studies compared them for predicting the morbidities in preterm infants. In this multicenter prospective observational study, SNAPPE-II and CRIB-II newborn illness severity scores were compared for predicting mortality and morbidities in infants with gestational age of ≤ 32 weeks. Major morbidities were classified as bronchopulmonary dysplasia, abnormal cranial ultrasound (presence of intraventricular hemorrhage grade III or more or periventricular leukomalacia grade II to IV), and retinopathy of prematurity requiring treatment. Combined adverse outcome was defined as death or any major morbidity. Comparison of the scoring systems was done by area under the curve (AUC) on receiver operating characteristics curve (ROC curve) analysis. A total of 419 neonates who were admitted to 5 participating NICUs were studied. The mortality rate in the study population was 8.8%. Both CRIB-II (AUC: 0.795) and SNAPPE-II (AUC: 0.78) had good predictive ability for in-hospital mortality. For predicting any one of the major morbidities and combined adverse outcome, CRIB-II had better predictive ability than SNAPPE-II with AUC of 0.83 vs. 0.70 and 0.85 vs. 0.74, respectively. CONCLUSION: In infants with gestational age of ≤ 32 weeks, both CRIB-II and SNAPPE-II are good scoring systems for predicting mortality. CRIB-II, being a simpler scoring system and having better predictive ability for major morbidities and combined adverse outcome, is preferable over SNAPPE-II. WHAT IS KNOWN: • SNAPPE-II and CRIB-II scores have good predictive ability on in-hospital mortality in preterm neonates. WHAT IS NEW: • SNAPPE-II and CRIB-II both have good predictive ability for mortality, but CRIB-II has better ability for short-term morbidities related to the prematurity.

Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study.

BACKGROUND: Neonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs. METHODS: The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality. FINDINGS: Between Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69-234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04-74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37-2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life. INTERPRETATION: Findings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs. FUNDING: Bill & Melinda Gates Foundation.

Premedication with Fentanyl for Less Invasive Surfactant Application (LISA): A Randomized Controlled Trial.

INTRODUCTION: Currently, there is no consensus regarding analgesic premedication before the surfactant administration by less invasive surfactant application (LISA) procedure. In this randomized controlled trial, we compared the level of comfort of preterm infants receiving fentanyl as analgesic and sedative versus no fentanyl during LISA procedure. METHODS: We randomized 34 preterm infants of 28+0-33+6 weeks of gestation with respiratory distress syndrome (RDS) within 6 h of birth to receive either fentanyl (1 µg/kg intravenous) or no premedication during surfactant administration by LISA procedure. Primary objective was to assess the proportion of preterm infants to be comfortable during the procedure [revised premature infant pain profile (R-PIPP) score ≤12] and secondarily complications occurring during the procedure, hemodynamically significant patent ductus arteriosus (hsPDA), intraventricular hemorrhage (IVH) (≥ grade 3), bronchopulmonary dysplasia (BPD) and composite outcome of BPD/mortality. RESULTS: Proportion of preterm infants with a R-PIPP score ≤12 during LISA was significantly higher in the fentanyl group [15/17 (88.23%) vs. 8/17 (47.05%); p value 0.025]. There were no differences in secondary outcome parameters. CONCLUSION: Low-dose fentanyl during LISA procedure resulted in more comfort in preterm infants and without increased complication of both the LISA procedure and fentanyl administration. Further studies are needed to determine the safest and most effective pharmacologic measures to prevent pain and discomfort during LISA.

Respiratory distress syndrome (RDS) in neonates is associated with prematurity, and surfactant administration is essential for its management. Surfactant instillation through a thin intratracheal catheter in spontaneously breathing infants with nasal continuous positive airway pressure (nCPAP) is known as less invasive surfactant application (LISA). Till date, there is no consensus regarding analgesic premedication before the surfactant administration by LISA procedure. In this randomized controlled trial, we compared the level of comfort of preterm infants receiving fentanyl as analgesic and sedative versus no fentanyl during LISA procedure. We reported that proportion of preterm infants with severe pain during LISA was significantly lower in the fentanyl group. There were no differences in clinical outcome parameters. So, we concluded that low-dose fentanyl during LISA procedure resulted in more comfort in preterm infants and without increased complication of both the LISA procedure and fentanyl administration.

Short-term Outcome and Predictors of Survival Among Neonates with Moderate or Severe Hypoxic Ischemic Encephalopathy: Data From the Indian Neonatal Collaborative.

BACKGROUND: Among term and late preterm infants, hypoxic ischemic encephalopathy (HIE) is an important cause of mortality, and neurologic morbidity among survivors. OBJECTIVE: The primary objective was to study the incidence of survival to discharge among late preterm and term infants with moderate or severe HIE. Secondary objectives were to explore variation in the management of HIE across participating sites and to identify the predictors of survival. SETTING: Indian Neonatal Collaborative (INNC), a network of 28 neonatal units in India. STUDY DESIGN: Retrospective cohort. PARTICIPANTS: Late preterm (34-36 weeks) and term (37-42 weeks) infants with moderate to severe HIE from 2018-2019. OUTCOME: The primary outcome was survival to discharge (including discharged home and transfer to other hospital). A multivariate logistic regression model was constructed to identify the predictors of survival. RESULTS: Of 352 infants with moderate or severe HIE, 59% received therapeutic hypothermia. Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE (aOR 0.04; 95% CI 0.02-0.10), persistent pulmonary hypertension (PPHN) (aOR 0.22; 95% CI 0.08-0.61) and requirement of epinephrine during resuscitation (aOR 0.21; 95% CI 0.05-0.84) were independently associated with decreased odds of survival to discharge. CONCLUSION: Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE, requirement of epinephrine during resuscitation and PPHN decreased the odds of survival.

Ventricular function in congenital diaphragmatic hernia: a systematic review and meta-analysis.

There is emerging evidence supporting ventricular function as a prognostic factor in congenital diaphragmatic hernia (CDH). The present systematic review and meta-analysis aimed to determine the predictive value of early ventricular function for survival and extracorporeal membrane oxygenation (ECMO) requirement in newborns with CDH. PubMed, Google Scholar, Cochrane Central Register, Clinical Trial Registry, and Opengrey were accessed. Studies evaluating associations between echocardiographic ventricular function measured ≤ 48 h after birth and survival or ECMO requirement were included. Two independent authors extracted the following data: study and participant characteristics, prognostic factors, and outcome-related data. Eleven studies met the inclusion criteria. Five studies reported on survival, two on ECMO, and four on both outcomes. A moderate risk of bias was found in most of the studies, mainly because of selection, prognostic factors, and confounding biases. For survival (899 participants), pooled sensitivity and specificity were 86% (95% confidence interval [CI], 77-92%) and 44% (95% CI, 25-65%), respectively, in normal left ventricular function. For ECMO need (815 participants), pooled sensitivity and specificity were 39.8% (95% CI, 27-52%) and 88% (95% CI, 80-96%), respectively, in left ventricular dysfunction. Overall certainty of the evidence was graded very low for survival and low for ECMO. Inconsistent reporting of echocardiographic measurements and lack of adjustment for confounding factors were major limitations.Conclusion: Early ventricular dysfunction is a potential prognostic factor in CDH. Standardized echocardiographic measurement reporting and high-quality studies are needed to further elucidate its prognostic significance. What is Known: • Evidence supports the predictive value of echocardiographic measurements in CDH ≤ 24-48 h post-birth. • Ventricular dysfunction has been proposed as a prognostic risk factor. What is New: • Right and left ventricular functions were promising predictors of survival and ECMO requirement in neonates with CDH. • Test characteristics of ventricular function were determined as predictors of survival or need for ECMO. Specific echocardiographic markers of ventricular function can be valuable in determining prognosis.

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS).

BACKGROUND: Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin-gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. METHODS: In BARNARDS, consenting mother-neonates aged 0-60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic-pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. FINDINGS: Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin-gentamicin, ceftazidime-amikacin, piperacillin-tazobactam-amikacin, and amoxicillin clavulanate-amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime-amikacin than for neonates treated with ampicillin-gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14-0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin-gentamicin; 286 (73·3%) to amoxicillin clavulanate-amikacin; 301 (77·2%) to ceftazidime-amikacin; and 312 (80·0%) to piperacillin-tazobactam-amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin-gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate-amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime-amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin-tazobactam-amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis. INTERPRETATION: Our data raise questions about the empirical use of combined ampicillin-gentamicin for neonatal sepsis in LMICs because of its high resistance and high rates of frequency of resistance and low probability of target attainment. Accessibility and affordability need to be considered when advocating antibiotic treatments with variance in economic health structures across LMICs. FUNDING: The Bill & Melinda Gates Foundation.

Nasal HFOV versus nasal IPPV as a post-extubation respiratory support in preterm infants-a randomised controlled trial.

Early and successful extubation prevents several morbidities in preterm newborns. Several secondary non-invasive respiratory modalities exist but with their merits and demerits. Given the benefits of nasal high-frequency oscillatory ventilation (nHFOV), we tried to examine whether nHFOV could reduce reintubation rates compared to nasal intermittent positive pressure ventilation (NIPPV) during the post-extubation phase in preterm infants. Stratified randomisation based on gestational age was done for 86 mechanically ventilated preterm infants between 26 and 36+6 weeks of gestation within 2 weeks of age to receive either nHFOV or NIPPV post-extubation. The main objective was to compare extubation failure within 72 h following extubation and secondarily feed intolerance, intraventricular haemorrhage (IVH) (> grade 3), composite bronchopulmonary dysplasia (BPD)/mortality, composite duration of oxygen supplementation/ventilation support and SpO2/FiO2 ratio. No statistical difference was noted for primary outcome (RR 0.8, 95% CI: 0.23 to 2.78; p = 1.00) and secondary outcomes. However, nHFOV appeared possibly better in respect to feed tolerance rates and pCO2 washout.Conclusion: Extubation failure within 72 h in infants less than 37 weeks of gestation did not differ between the two groups. However, nHFOV seems promising in reducing enteral feeding issues and pCO2 elimination. Larger multicentre studies are required for exploring benefits of nHFOV.Trial registration: www.ctri.nic.in id CTRI/2019/07/020055, registration date July 5, 2019 What is Known: • NIPPV is superior to nCPAP as a secondary mode of respiratory support. • Synchronisation is preferred for optimum ventilation. What is New: • nHFOV, a novel non-invasive respiratory modality without need for synchronisation, appears promising as a secondary mode subject to further trials. • It seems promising in reducing enteral feeding issues and pCO2 elimination.

Overexpression of Efflux Pumps, Mutations in the Pumps' Regulators, Chromosomal Mutations, and AAC(6')-Ib-cr Are Associated With Fluoroquinolone Resistance in Diverse Sequence Types of Neonatal Septicaemic Acinetobacter baumannii: A 7-Year Single Center Study.

This study investigates susceptibility toward three fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin), multiple fluoroquinolone-resistance mechanisms, and epidemiological relationship of neonatal septicaemic Acinetobacter baumannii. Previous studies on fluoroquinolone resistance in A. baumannii focused primarily on ciprofloxacin susceptibility and assessed a particular mechanism of resistance; a more holistic approach was taken here. Epidemiological relationship was evaluated by Multi Locus Sequence Typing. Minimum Inhibitory Concentrations of fluoroquinolones was determined with and without efflux pump inhibitors. Overexpression of efflux pumps, resistance-nodulation-cell-division (RND)-type, and multidrug and toxic compound extrusion (MATE)-type efflux pumps were evaluated by reverse transcriptase-qPCR. Mutations within regulatory proteins (AdeRS, AdeN, and AdeL) of RND-pumps were examined. Chromosomal mutations, presence of qnr and aac(6')-Ib-cr were investigated. A. baumannii were highly diverse as 24 sequence-types with seven novel STs (ST-1440/ST-1441/ST-1481/ST-1482/ST-1483/ST-1484/ST-1486) were identified among 47 A. baumannii. High resistance to ciprofloxacin (96%), levofloxacin (92%), and particularly moxifloxacin (90%) was observed, with multiple mechanisms being active. Resistance to 4th generation fluoroquinolone (moxifloxacin) in neonatal isolates is worrisome. Mutations within GyrA (S83L) and ParC (S80L) were detected in more than 90% of fluoroquinolone-resistant A. baumannii (FQRAB) spread across 10 different clonal complexes (CC1/CC2/CC10/CC25/CC32/CC126/CC149/CC216/CC218/CC513). Efflux-based FQ resistance was found in 65% of FQRAB with ≥2 different active pumps in 38% of strains. Overexpression of adeB was highest (2.2-34-folds) followed by adeJ, adeG, and abeM. Amino acid changes in the regulators (AdeRS/AdeN/AdeL) either as single or multiple substitutions substantiated the overexpression of the pumps. Diverse mutations within AdeRS were detected among different CCs whereas mutations within AdeN linked to CC10 and CC32. Chromosomal mutations and active efflux pumps were detected simultaneously among 64% of FQRAB. Presence of aac(6')-Ib-cr was also high (74% of FQRAB) but qnrS were absent. As most FQRABs had chromosomal mutations, this was considered predominant, however, isolates where pumps were also active had higher MIC values, establishing the critical role of the efflux pumps. The high variability of FQ susceptibility among FQRAB, possessing the same set of mutations in gyrA, parC, and efflux pump regulators, was also noted. This reveals the complexity of interpreting the interplay of multiple resistance mechanisms in A. baumannii.

OXA-181-Like Carbapenemases in Klebsiella pneumoniae ST14, ST15, ST23, ST48, and ST231 from Septicemic Neonates: Coexistence with NDM-5, Resistome, Transmissibility, and Genome Diversity.

Studies on the epidemiology and genomes of isolates harboring OXA-48-like genes in septicemic neonates are rare. Here, isolates producing these carbapenemases which emerged and persisted in an Indian neonatal unit were characterized in terms of their resistome, transmissibility, and genome diversity. Antibiotic susceptibility and whole-genome sequencing were carried out. The sequence types, resistome, virulome, mobile genetic elements, and transmissibility of carbapenem-resistant plasmids were evaluated. Core genome analysis of isolates was shown in a global context with other OXA-48-like carbapenemase-harboring genomes, including those from neonatal studies. Eleven OXA-48-like carbapenemase-producing Klebsiella pneumoniae (blaOXA-181, n = 7 and blaOXA-232, n = 4) isolates belonging to diverse sequence types (ST14, ST15, ST23, ST48, and ST231) were identified. blaOXA-181/OXA-232 and blaNDM-5 were found in a high-risk clone, ST14 (n = 4). blaOXA-181/OXA-232 were in small, nonconjugative ColKP3 plasmids located on truncated Tn2013, whereas blaNDM-5 was in self-transmissible, conjugative IncFII plasmids, within truncated Tn125 Conjugal transfer of blaOXA-181/OXA-232 was observed in the presence of blaNDM-5 The study strains were diverse among themselves and showed various levels of relatedness with non-neonatal strains from different parts of the world and similarity with neonatal strains from Tanzania and Ghana when compared with a representative collection of carbapenemase-positive K. pneumoniae strains. We found that blaOXA-181/OXA-232-harboring isolates from a single neonatal unit had remarkably diverse genomes, ruling out clonal spread and emphasizing the extent of plasmid spreading across different STs. This study is probably the first to report the coexistence of blaOXA-181/232 and blaNDM-5 in neonatal isolates.IMPORTANCE Neonatal sepsis is a leading cause of neonatal mortality in low- and middle-income countries (LMICs). Treatment of sepsis in this vulnerable population is dependent on antimicrobials, and resistance to these life-saving antimicrobials is worrisome. Carbapenemases, enzymes produced by bacteria, can make these antimicrobials useless. Our study describes how OXA-48-like carbapenemases in neonatal septicemic Klebsiella pneumoniae shows remarkable diversity in the genomes of the strains and relatedness with strains from other parts of world and also to some neonatal outbreak strains. It is also the first to describe such resistance due to coproduction of dual carbapenemases, (OXA)-48 and New Delhi metallo-ß-lactamase-5, in Klebsiella pneumoniae from neonatal settings. Carbapenemase genes situated on plasmids within high-risk international clones, as seen here, increase the ease and transfer of resistant genetic material. With the WHO treatment protocols not adequately poised to handle such infections, prompt attention to neonatal health care is required.