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.

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.

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.

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.

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.

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.

Minimally invasive surfactant therapy versus InSurE in preterm neonates of 28 to 34 weeks with respiratory distress syndrome on non-invasive positive pressure ventilation-a randomized controlled trial.

Preterm neonates with respiratory distress syndrome (RDS) are commonly treated with surfactant by intubate surfactant extubate (InSurE) technique. Mode of surfactant administration has evolved towards less invasive technique in the last few years. We randomised 58 preterm infants of 28-34 weeks of gestation with RDS within 6 h of birth to receive surfactant by InSurE or minimally invasive surfactant therapy (MIST). Non-invasive positive pressure ventilation (NIPPV) was used as primary respiratory support. The main objective was to compare the need of invasive mechanical ventilation (IMV) in first 72 h of life and secondarily hemodynamically significant patent ductus arteriosus (hsPDA), intraventricular haemorrhage (IVH) (> grade 2), bronchopulmonary dysplasia (BPD) and composite outcome of BPD/mortality. We did not find any difference in need of IMV in first 72 h between MIST and InSurE (relative risk with MIST, 0.62; 95% confidence interval, 0.22 to 1.32). No difference was observed in terms of hs PDA, IVH (> grade 2), BPD and composite outcome of BPD/mortality.Conclusion: There is no difference between MIST and InSurE in preterm neonates with RDS with NIPPV as a primary mode of respiratory support. Larger multicentre studies are needed to further explore differences in treatment failure and other secondary outcomes.Trial registration: www.ctri.nic.in id CTRI/2019/03/017992, registration date March 8, 2019. What is Known • InSurE is commonly used for many years for treatment of RDS in preterm neonates. • MIST has been introduced as a newer tool. What is New • MIST with feeding tube is comparable with InSurE in preterm infants with RDS in developing countries. •NIPPV can be used as primary respiratory support for MIST.

Predictors of length of hospital stay among preterm infants admitted to neonatal intensive care unit: Data from a multicentre collaborative network from India (INNC: Indian National Neonatal Collaborative).

AIM: Prediction of length of stay (LOS) among preterm neonates is important for counselling of parents and for assessing neonatal intensive care unit (NICU) census and economic burden. The aim of this study is to evaluate perinatal and postnatal factors that influence LOS in preterm infants (25-33 weeks of gestation) admitted to participating NICUs of Indian National Neonatal Collaborative (INNC). METHODS: From the INNC database, the data which were prospectively entered using uniformed pre-defined criteria were analysed. RESULTS: A total of 3095 infants were included from 12 centres. Every week decrease in gestation increased LOS by 9 days. The median LOS for infants with gestational age of 25, 26, 27, 28, 29, 30, 31, 32 and 33 weeks were 86, 70, 62, 52, 40, 30, 23, 16 and 10 days, respectively. On multivariate analysis, abnormal antenatal umbilical artery doppler, severe small for gestational age (SGA), requirement of resuscitation, respiratory distress syndrome (RDS), seizures, sepsis, necrotising enterocolitis (NEC), major malformations and bronchopulmonary dysplasia (BPD) increased LOS by 5.4 (3.5-7.4), 21.6 (19-23.9), 4.7 (3.3-6.1), 3 (1.7-4.3), 15.2 (8.5-22.1), 11.2 (9.1-13.2), 9.8 (5.2-14.4), 8.8 (4.4-13.3) and 5.6 (0.5-10.7) days, respectively. CONCLUSIONS: Apart from lower gestation and birth weight, abnormal antenatal umbilical artery doppler, severe SGA, resuscitation need, major malformations, RDS, seizures, sepsis, NEC and BPD influenced LOS in preterm infants. In comparison with other networks or data from developed countries, LOS in our network was comparatively less for similar gestational age infants.

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).

Thyroid Function Test in Preterm Neonates: Normative Data.

Introduction: Initial surge of thyroid-stimulating hormone (TSH) in neonates increases free and total triiodothyronine (T3) and tetraiodothyronine (T4) in 24-36 hours following birth, and the effect then gradually wanes off. As somatic and intellectual development is dependent on normal thyroid function especially in infancy, normative data in these children may be of immense value to diagnose hypothyroidism in this subset of infants. Comprehensive normative values of thyroid function parameters in preterm neonates are scarcely available. The objective of this study was to determine the normative value of thyroid function parameters in preterm neonates. Methods: Preterm neonates (n = 102) born at 34 and 35 weeks of gestation of euthyroid mothers from an iodine-sufficient population were evaluated for T3, T4, free thyroxine (FT4) and TSH during 3-7 days after birth and again after 1 month. The expected date of delivery (EDD) and Ballard score were used to identify the duration of gestation. Results: The mean gestational age was 34.7 ± 0.41 weeks. The mean (± SD) for T3 (ng/dl), T4 (µg/dl), FT4 (ng/ml) and TSH (µIU/ml) on days 3-7 following birth was as follows: 156 ± 44.6, 12.8 ± 3.7, 1.50 ± 0.54 and 7.13 ± 6.04, respectively. Around 4 weeks of age, values changed to 104 ± 38.4, 12.1 ± 4.02, 1.46 ± 0.42 and 3.25 ± 2.85, respectively. All parameters changed significantly around 4 weeks, except FT4. None of the parameters were correlated with gestational age or body weight at birth. Normative values for each parameter in percentiles were generated. Conclusion: This study generated the normative values of the thyroid function test during the first week and after around 4 weeks of life for premature neonates (born at 34-35 weeks).

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.

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.

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.

Noninvasive high-frequency oscillation ventilation as post- extubation respiratory support in neonates: Systematic review and meta-analysis.

INTRODUCTION: Noninvasive High-Frequency Oscillatory Ventilation (NHFOV) is increasingly being adopted to reduce the need for invasive ventilation after extubation. OBJECTIVES: To evaluate the benefits and harms of NHFOV as post-extubation respiratory support in newborns compared to other non-invasive respiratory support modes. MATERIAL & METHODS: We included randomized controlled trials comparing NHFOV with other non-invasive modes post-extubation in newborns. Data sources were MEDLINE (via Pubmed), Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, WHO international clinical trials registry platform and Clinical Trial Registry, forward and backward citation search. Methodological quality of studies was assessed by Cochrane's Risk of Bias tool 1.0. RESULTS: This systematic review included 21 studies and 3294 participants, the majority of whom were preterm. NHFOV compared to nasal continuous positive airway pressure (NCPAP) reduced reintubation within seven days (RR 0.34, 95% CI 0.22 to 0.53) after extubation. It also reduced extubation failure (RR 0.39, 95% CI 0.30 to 0.51) and reintubation within 72 hrs (RR 0.40, 95% CI 0.31 to 0.53), bronchopulmonary dysplasia (RR 0.59, 95% CI 0.37 to 0.94) and pulmonary air leak (RR 0.46, 95% CI 0.27 to 0.79) compared to NCPAP. The rate of reintubation within seven days (RR 0.62, 95% CI 0.18 to 2.14) was similar whereas extubation failure (RR 0.65, 95% CI 0.50 to 0.83) and reintubation (RR 0.68, 95% CI 0.52 to 0.89) within 72 hrs were lower in NHFOV group compared to nasal intermittent positive pressure ventilation. There was no effect on other outcomes. Overall quality of the evidence was low to very low in both comparisons. CONCLUSIONS: NHFOV may reduce the rate of reintubation and extubation failure post-extubation without increasing complications. Majority of the trials were exclusively done in preterm neonates. Further research with high methodological quality is warranted.

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.

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.

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.

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.

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.