Milrinone in persistent pulmonary hypertension of newborn: a scoping review.

Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition in newborns admitted to the neonatal intensive care units (NICUs). PPHN has still a high mortality and morbidity. Inhaled nitric oxide (iNO) is the first line vasodilator therapy for PPHN in high income countries. In low-to-middle income countries (LMICs), availability of iNO remains scarce and expensive. The purpose of this scoping review was to evaluate the current existing literature for milrinone therapy in PPHN and to identify the knowledge gaps in milrinone use in infants with PPHN. The available evidence for milrinone remains limited both as monotherapy and as an adjuvant to iNO. The studies were heterogeneous, conducted in different settings, with different populations and more importantly the endpoints of these trials were short-term outcomes such as changes in oxygenation and blood pressure. Large prospective studies investigating long-term outcomes, mortality, and the need for Extracorporeal membrane oxygenation (ECMO) are warranted. Randomized controlled trials with milrinone as monotherapy are needed in LMICs where iNO availability remains limited. IMPACT: Milrinone has a potential role in the management of PPHN both as an adjuvant to iNO as well as a monotherapy. This scoping review identified the problems existing in the published literature on milrinone and the barriers to generalization of these results. Multi-centre randomized controlled trials on milrinone, especially involving centers from low- and middle-income countries are needed, where it can be evaluated as first-line pulmonary vasodilator therapy.

Positive Pressure Ventilation in Preterm Infants in the Delivery Room: A Review of Current Practices, Challenges, and Emerging Technologies.

BACKGROUND: A major proportion of preterm neonates require positive pressure ventilation (PPV) immediately after delivery. PPV may be administered through a face mask (FM) or nasal prongs. Current literature indicates that either of these are associated with similar outcomes. SUMMARY: Nonetheless, FM remains the most utilized and the best choice. However, most available FM sizes are too large for extremely preterm infants, which leads to mask leak and ineffective PPV. Challenges to providing effective PPV include poor respiratory drive, complaint chest wall, weak thoracic muscle, delayed liquid clearance, and surfactant deficiency in preterm infants. Mask leak, airway obstruction, poor technique, and inappropriate size are correctable causes of ineffective PPV. Visual assessment of chest rise is often used to assess the efficacy of PPV. However, its accuracy is debatable. Though end tidal CO2 may adjudge the effectiveness of PPV, clinical studies are limited. The compliance of a preterm lung is highly dynamic. The inflating pressure set on T-piece is constant throughout the resuscitation, but the lung volume and dynamics changes with every breath. This leads to huge fluctuations of tidal volume delivery and can trigger inflammatory cascade in preterm infants leading to brain and lung injury. Respiratory function monitoring in the delivery room has potential for guiding and optimizing delivery room resuscitation. This is, however, limited by high costs, complex information that is difficult to interpret during resuscitation, and absence of clinical trials. KEY MESSAGES: This review summarizes the existing literature on PPV in preterm infants, the various aspects related to it such as the pathophysiology, interfaces, devices utilized to deliver it, appropriate technique, emerging technologies, and future directions.

Allogeneic Umbilical Cord Plasma Eyedrops for the Treatment of Recalcitrant Dry Eye Disease Patients.

BACKGROUND: Dry eye disease is a significant disease in Singapore. While there have been studies using allogenic cord serum for the treatment of dry eye disease, treatment of dry eyes with allogenic umbilical cord plasma drops has yet to be started in Singapore. PURPOSE: To evaluate the effectiveness of umbilical cord plasma eyedrops for the treatment of recalcitrant dry eyes in a local Singaporean context. METHODS: This is an observational, longitudinal, interventional study for dry eye patients who did not show clear improvement after standard therapy. Patients were recruited from 2020 to 2023 from the dry eye clinic of the Singapore National Eye Center. Umbilical cord plasma was delivered frozen to patients and stored in home freezers. All participants underwent a standardized clinical evaluation for dry eye, and data were collected. RESULTS: There were 40 participants (7 males and 33 females). The duration of follow-up was 5.52 ± 1.57 months. Kerato-epitheliopathy staining score, TBUT (tear breakup time), and SPEED (Standard Patient Evaluation of Eye Dryness Questionnaire) scores significantly improved after treatment. No statistically significant improvement was found in terms of visual acuity, according to Schirmer's score. CONCLUSION: Cord plasma eye drops significantly improved kerato-epitheliopathy staining scores in recalcitrant dry eye patients. Allogeneic plasma is a promising form of treatment for recalcitrant dry eye.

A Case of Posttransplant Fibrillary Glomerulonephritis.

Fibrillary glomerulonephritis (FGN) is a rare form of glomerulonephritis, usually occurring in concurrence with other conditions such as hepatitis C, dysproteinemia, autoimmune conditions, diabetes mellitus, and malignancy. The diagnosis is made by the presence of randomly oriented fibrillar deposits with a mean diameter of 20 nm, which stain positive for IgG and C3 and are negative for congo red and thioflavin T stains. Staining for DNAJB9 (DnaJ homolog subfamily B member 9) is a recently discovered mode of diagnosis of FGN without electron microscopy. The prognosis is poor and optimal treatment is yet not clearly defined, though rituximab may be useful in FGN patients with relatively preserved renal functions. In this case report, we discuss a case of post-renal transplant patient with de novo occurrence of fibrillary glomerulonephritis.

Antenatal Magnesium Sulfate and adverse gastrointestinal outcomes in Preterm infants-a systematic review and meta-analysis.

INTRODUCTION: To evaluate the effect of antenatal magnesium sulfate (MgSO4) on mortality and morbidity outcomes related to the gastrointestinal system (GI) in preterm infants. METHODS: Data sources: A systematic literature search was conducted in November 2022. PubMed, CINAHL Plus with Full Text (EBSCOhost), Embase (Elsevier), and CENTRAL (Ovid) were searched. There were 6695 references. After deduplication, 4332 remained. Ninety-nine full-text articles were assessed and forty four articles were included in the final analysis. STUDY ELIGIBILITY CRITERIA: Randomized or quasi-randomized clinical trials and observational studies that evaluated at least one of the pre-specified outcomes were included. Preterm infants whose mothers were given antenatal MgSO4 were included and whose mothers did not receive antenatal MgSO4 were the comparators. The main outcomes and measures were: Necrotizing enterocolitis (NEC) (stage ≥ 2), surgical NEC, spontaneous intestinal perforation (SIP), feeding intolerance, time to reach full feeds, and GI-associated mortality. STUDY APPRAISAL AND SYNTHESIS METHODS: A random-effects model meta-analysis was performed to yield pooled OR and its 95% CI for each outcome due to expected heterogeneity in the studies. The analysis for each predefined outcome was performed separately for adjusted and unadjusted comparisons. All included studies were assessed for methodological quality. The risk of bias was assessed using elements of the Cochrane Collaboration's tool 2.0 and the Newcastle-Ottawa Scale for randomized controlled trials (RCTs) and non-randomized studies (NRS), respectively. The study findings were reported as per PRISMA guidelines. RESULTS: A total of thirty-eight NRS and six RCTs involving 51,466 preterm infants were included in the final analysis. There were no increased odds of stage ≥2 NEC, (NRS : n = 45,524, OR: 0.95; 95% CI: 0.84-1.08, I2- 5% & RCT's: n = 5205 OR: 1.00; 95% CI: 0.89-1.12, I2- 0%), SIP (n = 34,186, OR: 1.22, 95% CI: 0.94-1.58, I2-30%), feeding intolerance (n = 414, OR: 1.06, 95% CI: 0.64-1.76, I2-12%) in infants exposed to antenatal MgSO4. On the contrary, the incidence of surgical NEC was significantly lower in MgSO4 exposure infants (n = 29,506 OR:0.74; 95% CI: 0.62-0.90, ARR: 0.47%). Studies assessing the effect on GI-related mortality were limited to make any conceivable conclusion. The certainty of evidence (CoE) for all outcomes was adjudged as 'very low' as per GRADE. CONCLUSION: Antenatal magnesium sulfate did not increase the incidence of gastrointestinal-related morbidities or mortality in preterm infants. With the current evidence concerns, regarding the adverse effects of MgSO4 administration leading to NEC/SIP or GI-related mortality in preterm infants should not be a hurdle in its routine use in antenatal mothers.

Special Issue: Advances in Healthcare for Neonates.

We are delighted to present an editorial for the Special Issue 'Advances in Healthcare for Neonates' [...].

Initial Use of 100% but Not 60% or 30% Oxygen Achieved a Target Heart Rate of 100 bpm and Preductal Saturations of 80% Faster in a Bradycardic Preterm Model.

Background: Currently, 21−30% supplemental oxygen is recommended during resuscitation of preterm neonates. Recent studies have shown that 58% of infants < 32 week gestation age are born with a heart rate (HR) < 100 bpm. Prolonged bradycardia with the inability to achieve a preductal saturation (SpO2) of 80% by 5 min is associated with mortality and morbidity in preterm infants. The optimal oxygen concentration that enables the achievement of a HR ≥ 100 bpm and SpO2 of ≥80% by 5 min in preterm lambs is not known. Methods: Preterm ovine model (125−127 d, gestation equivalent to human neonates < 28 weeks) was instrumented, and asphyxia was induced by umbilical cord occlusion until bradycardia. Ventilation was initiated with 30% (OX30), 60% (OX60), and 100% (OX100) for the first 2 min and titrated proportionately to the difference from the recommended preductal SpO2. Our primary outcome was the incidence of the composite of HR ≥ 100 bpm and SpO2 ≥ 80%, by 5 min. Secondary outcomes were to evaluate the time taken to achieve the primary outcome, gas exchange, pulmonary/systemic hemodynamics, and the oxidative injury. Results: Eighteen lambs (OX30-6, OX60-5. OX100-7) had an average HR < 91 bpm with a pH of <6.92 before resuscitation. Sixty seven percent achieved the primary outcome in OX100, 40% in OX60, and none in OX30. The time taken to achieve the primary outcome was significantly shorter with OX100 (6 ± 2 min) than with OX30 (10 ± 3 min) (* p = 0.04). The preductal SpO2 was highest with OX100, while the peak pulmonary blood flow was lowest with OX30, with no difference in O2 delivery to the brain or oxidative injury by 10 min. Conclusions: The use of 30%, 60%, and 100% supplemental O2 in a bradycardic preterm ovine model did not demonstrate a significant difference in the composite primary outcome. The current recommendation to use 30% oxygen did not achieve a preductal SpO2 of 80% by 5 min in any preterm lambs. Clinical studies to optimize supplemental O2 in depressed preterm neonates not requiring chest compressions are warranted.

Alloimmune Neutropenia in a Neonate: Case Report and Review of Literature.

Neonatal alloimmune neutropenia, variably referred to in the literature as NAIN, FNAIN or NIN, is a disorder of neutrophil destruction in newborns similar to better-known conditions such as hemolytic disease of the newborn and neonatal alloimmune thrombocytopenia (FNAIT). Infants affected by this self-limiting condition can present asymptomatically or have a wide range of symptoms, from skin manifestations and mucositis to severe infections such as sepsis and pneumonia. In our case, we report an otherwise asymptomatic term infant born with severe neutropenia to a mother affected by COVID-19 in the 3rd trimester. However, it is unclear if COVID-19 contributed to our patients' neutropenia. Diagnostic testing eventually revealed the presence of anti-neutrophil antibodies, confirming the diagnosis of alloimmune neutropenia. The infant was conservatively managed with early discharge prior to resolution of neutropenia and close post-discharge follow up.

Multicenter evaluation of the IL-3-pSTAT5 assay to assess the potency of cryopreserved stem cells from cord blood units: The BEST Collaborative study.

BACKGROUND: The IL-3-pSTAT5 assay, a new, rapid, and standardized flow-cytometry-based assay may compensate for several limitations of the colony-forming unit (CFU) assay typically used for stem cell potency assessments of cord blood units (CBU). We performed an inter-laboratory evaluation of the performance of this new assay. STUDY DESIGN AND METHODS: This Biomedical Excellence for Safer Transfusion (BEST) Collaborative multicenter, international study included 15 participants from public cord blood banks (CBBs), CBB-supporting research laboratories, and stem cell laboratories. To perform the IL-3-pSTAT5 assay, participating centers received reagents, instructions, and 10 blind CBU samples, including eight normal samples and two samples exposed to a transient warming event. We measured inter-laboratory agreement qualitatively (proportion of correctly classified samples) and quantitatively (coefficient of variation [CV], correlation coefficients, receiver operating characteristics (ROC) curve, and intraclass correlation coefficient [ICC]). RESULTS: The qualitative agreement was 97.3% (i.e., 107/110; Fleiss' kappa = 0.835). The average CV on a per-sample basis was 11.57% among all samples, 8.99% among normal samples, and on a per-center basis was 9.42% among normal samples. In a correlation matrix that compared results across centers, the mean Pearson's correlation coefficient was 0.88 (standard deviation = 0.04). The ICC was 0.83 (95% confidence interval = 0.68-0.95). The area under the curve (AUC) from the ROC curve was 0.9974. DISCUSSION: Excellent qualitative and quantitative agreement was exhibited across laboratories. The IL-3-pSTAT5 assay may therefore be implemented in flow cytometry laboratories to rapidly and reliably provide standardized measures of stem cell potency in CBUs.

Uremic Optic Neuropathy: A Potentially Reversible Complication of Chronic Kidney Disease.

Uremic optic neuropathy (UON) is one of the rare causes of vision loss in chronic kidney disease patients. It is infrequently seen nowadays as most of the patients are dialyzed early owing to better availability of medical services. It is a clinical diagnosis, correlating loss of vision with optic disc edema in a patient with kidney failure which improves noticeably with hemodialysis and steroids. We describe a patient with UON with excellent improvement on timely institution of hemodialysis and steroid therapy.

Subjective Assessment of Sleep Quality and Excessive Daytime Sleepiness in Conventional Hemodialysis Population: A Single-Center Experience.

Introduction: Sleep disturbances are common in patients with end-stage kidney disease on hemodialysis (hemodialysis population: HDP). Higher rates of primary sleep disorders, demographic characteristics, metabolic abnormalities, and the efficacy of treatment place HDP at higher risk. The pattern observed is delayed onset of sleep, frequent awakening episodes, insomnia, sleep apnoea, excessive daytime sleepiness, restless leg syndrome, abnormal limb movements, pain in limbs, confusion, and nightmares. Two commonly used subjective assessment scores are the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality and the Epworth Sleepiness Scale (ESS) to assess excessive daytime sleepiness. Objective: Subjective assessment of sleep using PSQI and ESS scores in HDP and correlation with clinical and demographic characteristics. Patients and Methods: A cross-sectional descriptive study of 148 patients with ESKD undergoing in-center hemodialysis. From June 2021 to October 2021 in Madurai medical college, Madurai, India. Subjective assessment with PSQI and ESS scores was done to identify sleep quality and daytime sleepiness, respectively. Results: The median PSQI score was 6 (IQ:4-10), and as much as 68.24% scored >5 on the PSQI (poor sleepers). The median ESS score of the study participants was 4 (Iq range 3-7), and 19.59% had a total ESS score of more than 10 (excessive daytime sleepiness). The mean age of the participants was 44±14.5. Age more than 60, lower body mass index, unemployment, higher dialysis vintage of more than 2 years, lower hemoglobin, high calcium-phosphorus product are statistically significant for both PSQI and ESS scores. Conclusion: The prevalence of poor sleep quality and excessive daytime sleepiness is high in HDP. Subjective assessment scores (PSQI and ESS) on the bedside are valuable tools in identifying sleep quality and EDS where objective assessment methods are not feasible and will help in the short time identification and management of sleep disturbances.

Humoral response to viral vector COVID-19 vaccine in hemodialysis patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) vaccine is not readily available in many countries where dosing interval is spaced more than ideal. Patients with chronic kidney disease, especially those on maintenance hemodialysis, have a tendency for a reduced immune response. This study was undertaken to demonstrate the distinct humoral immune response to the viral vector COVID-19 vaccine in patients with kidney failure receiving maintenance hemodialysis. METHODS: The study was carried out with two cohorts: 1) patients receiving maintenance hemodialysis and 2) healthcare workers from the same dialysis center as controls, each group with 72 subjects. Participants received a dose of Covishield ChAdOx1 nCoV-19 coronavirus vaccine. The humoral immunological response was determined using electrochemiluminescence immunoassay which quantitatively measures antibodies to the severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain. RESULTS: All study subjects in the control group developed a humoral response (antibody titer of ≥0.8 U/mL), while only 64 of 72 in the dialysis group (88.9%) were responders. Age (ρ = -0.234, p = 0.04) and sodium level (ρ = 0.237, p = 0.04) correlated with low antibody titer in bivariate analysis. In multivariate analysis, only age (odds ratio, 1.10; 95% confidence interval, 1.01-1.22; p = 0.045) was associated with nonresponders. CONCLUSION: Our study demonstrated a weak antibody response of hemodialysis patients to the viral vector COVID-19 vaccine. Older age was associated with nonresponders. Evaluation of both humoral and cellular immunity after the second vaccine dose and serial antibody titers can help determine the need for booster shots.

Human leukocyte antigen allele and haplotype frequencies in Singapore bone marrow donors and cord blood units.

We describe the allele and haplotype frequencies seen in a volunteer unrelated bone marrow donor registry, a public cord blood bank, and donor/recipient samples processed by the Health Sciences Authority (HSA) in Singapore. Historical human leukocyte antigen (HLA) typing reports were anonymized and combined. They were checked for HLA typing nomenclature discrepancies or ambiguities using the HLA-net UNIFORMATE tool, and for analysis, the validated data were subsequently separated into Chinese, Malay, Indian, and "Others," according to the race classification system used in Singapore. Individual ethnic allele and haplotype frequencies were calculated with the HLA-net GENE[RATE] pipeline using basic statistics. The Basic Statistics Tool of HLA-net was used to estimate haplotype frequency using an expectation maximization algorithm, given a set of multi-allelic data pairs for a given HLA locus. The outputs downloaded from the site comprised plain text files with haplotype frequency estimates, results of a global linkage disequilibrium test, and standardized residuals (stdres) corresponding to deviations from expected frequencies. HLA typing results from 59,186 individuals met the inclusion criteria, yielding 118,372 analyzable alleles. In our study population, the haplotype A*33:03-B*58:01-C*03:02-DRB1*03:01～DQB1*02:01:01G with a frequency of 4.91% was the most common. This haplotype was also the most common among Singaporean Chinese donors. Consistent with the predominant Chinese population, haplotypes with a frequency greater than 1% were also the most frequently observed haplotypes in the Singaporean population. In the Malay donor population, the most common haplotype was A*33:03～B*44:03～C*07:01:01G～ DRB1*07:01-DQB1*02:01:01G, with a frequency of 3.41%, whereas within the Indian donor population, the most common haplotype was A*01:01-B*57:01-C*06:02～DRB1*07:01-DQB1*03:03, with a frequency of 3.42%. Haplotype diversity and composition statistics within donor pools provide HLA background data required for the targeted recruitment of donors to support the hematopoietic stem cell donor requirements of the country. These data may be used in the future to devise donor recruitment strategies for optimizing the donor pool through targeted publicity and accruals.

Respiratory Failure in an Extremely Premature Neonate with COVID-19.

Coronavirus disease 2019 (COVID-19), a condition associated with SARS-CoV-2, typically results in mild infection in infants and children. However, children with risk factors such as chronic lung disease and immunosuppression have higher risk of severe illness from COVID-19. We report a case of a 27-week-gestation extremely premature infant born to a mother with COVID-19 infection. The infant, initially treated for surfactant deficiency, developed worsening hypoxic respiratory failure on the fifth day of life requiring escalating ventilatory support, an elevated level of C-reactive protein, thrombocytopenia, and an elevated level of d-dimer. The infant was positive for SARS-CoV-2 by RT-PCR from Day 1 to Day 42 of his life. The infant responded to a seven-day course of dexamethasone with a gradually decreasing oxygen requirement and could be extubated to non-invasive ventilation by the end of the fifth week after birth. The infant is currently on home oxygen by nasal cannula. Prolonged shedding of the virus may be a unique feature of the disease in premature infants. Extreme prematurity, immature lungs, and an immunocompromised status may predispose these infants to severe respiratory failure and a prolonged clinical course. Instituting appropriate COVID-19 protocols to prevent the spread of the disease in the neonatal intensive care unit (NICU) is of utmost importance. Infection with SARS-CoV-2 may have implications in the management of extremely premature infants in the NICU.

Schwartz Jampel Syndrome (SJS)-One in a Million Syndrome.

Schwartz Jampel syndrome is a very rare genetically heterogenous disorder characterized by myotonia, typical facies, growth retardation and osteoarticular changes. Prevelance of this syndrome is <1 in 100000. 150 cases have been reported in medical literature so far. We hereby report this rare syndrome in neurology.

Discovery of a novel HLA-A*02 variant, HLA-A*02:402, in a Singaporean cord blood unit.

Nucleotide replacements in codons 145 and 149 of HLA-A*02:03:01 result in a new allele, HLA-A*02:402.