Unmasking a looming crisis: Escalating MIC of last resort drugs against MRSA isolates from a tertiary care hospital in Central India.

PURPOSE: The Centers for Disease Control and Prevention has classified methicillin-resistant S aureus (MRSA) as a serious public health threat. The escalating minimum inhibitory concentration (MIC) of standard anti-methicillin-resistant S aureus (MRSA) drugs within the susceptible range, known as "MIC creep," jeopardizes their effectiveness against MRSA infections, posing additional challenges in managing MRSA infections. This cross-sectional study was conducted in a tertiary care hospital in Central India to assess the susceptibility trends of clinical MRSA isolates against commonly used anti-MRSA drugs and to observe MIC creep, if any, over three years (2020-2022). METHODS: The study included 158 non-repetitive clinical MRSA isolates. The MICs of vancomycin, teicoplanin, and linezolid were determined in MRSA strains using agar dilution, while the MIC of daptomycin was performed by broth microdilution. MIC creep was assessed by calculating MIC50, MIC90, Modal MIC, G-mean MIC, and susceptible and resistant percentages for the fiscal years 2020, 2021, and 2022. RESULTS: Of the 158 MRSA isolates, none were resistant to vancomycin, teicoplanin, and daptomycin, but two showed resistance to linezolid (LRSA). However, fifteen isolates showed intermediate resistance to vancomycin (VISA), and five showed intermediate resistance to teicoplanin (TISA). MIC of these anti-MRSA drugs increased in 2021 and 2022 compared to 2020. G-mean MIC for vancomycin, teicoplanin, and linezolid in MRSA strains increased significantly over the study period, while daptomycin MIC remained relatively stable, with a slight increase in 2021 and 2022. There was a high resistance rate for clindamycin, doxycycline, and chloramphenicol among VISA, TISA, and LRSA isolates compared to MRSA. CONCLUSIONS: During the three years of the study, "MIC creep" was observed in vancomycin, teicoplanin, and linezolid and, to some extent, for daptomycin in MRSA strains. The recovery of VISA, TISA, and linezolid-resistant MRSAs is worrisome, suggesting possible MRSA treatment failure and being a forerunner of resistant strains.

Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry.

BACKGROUND: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. METHODS: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). RESULTS: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60-8.94); p = 0.003; univariate analysis] and [3.30 (1.11-9.82); p = 0.03]; multivariate logistic regression]. CONCLUSIONS: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses.

Bioanalysis of Endogenous Isotretinoin in Altered and Unaltered Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry Coupled with Electrospray Ionization.

Bioanalytical method development and validation of endogenous Isotretinoin with Isotretinoin D5 as internal standard was done as per current regulatory guidelines. The method is simple, rugged and sensitive enough to estimate endogenous Isotretinoin using the chromatography-tandem mass spectrometry technique. An alternative approach has been adopted for quantitative analysis of endogenous Isotretinoin in human plasma. Isotretinoin free matrix (surrogate matrix) was prepared and further used for the development and validation of Isotretinoin. The method was validated in altered and unaltered plasma. The chromatographic optimization was done with column (ACE C18, 100 × 4.6 mm I.D. 5 µm particle size), using a mobile phase containing 1 mM ammonium acetate, pH 3.0 as a solvent A and solvent B (1 mM ammonium acetate (pH 3.0) with acetonitrile in a ratio of 10:90). A flow rate was set at 0.75 mL/min in a binary gradient mode. The analyte was recovered by liquid-liquid extraction method with diethyl ether as an extraction solvent. Multi-reaction monitoring mode in negative polarity was implemented for the quantification of endogenous Isotretinoin in plasma. The calibration curve of Isotretinoin was linear (r2 > 0.9992) over the concentration range of 0.5-1000 ng/mL. The intra-day precision was found in a range of 2.0-3.9% CV for altered samples and 0.9-3.7% CV for unaltered samples. The inter-day precision was found 2.6-6.1% CV for altered samples and 1.3-3.8% CV for unaltered samples. The average recovery of the extraction procedure was found 64.6% for altered samples and 62.2% for unaltered samples.

Synergism of CD28 Immune Molecule in Late Immunosuppressive Phase of COVID-19: Effectiveness in Vaccinated Individuals.

Context: Lymphopenia has been frequently documented and linked to coronavirus disease 2019 (COVID-19) in a severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) attack. A decrease in the T-lymphocyte count has shown promise as a clinical indicator and predictor of COVID-19 severity. Objective: The review intended to examine the relationship of COVID-19 infections in individuals to lost expression of CD28 on naive CD4+/CD8+-mediated, vaccine-specific, neutralizing antibody responses. Design: The research team performed a narrative review by searching eight databases: Medline, Elsevier, Cochrane, PubMed, Google Scholar, Mendeley, and Springer Nature. The search used the following key terms: SARS CoV-2, clinical aspects and pathology of SARS CoV-2, involvement of viral spike (S) protein in SARS CoV-2, immunological changes in COVID-19 infection, basic overview of CD28 immuno-molecule ligand, reduction of vaccine therapeutic efficacy in COVID-19 infection, and immunomodulatory response of lost CD28 ligand. Setting: This study was done in a Maharishi Arvind College of Pharmacy, Jaipur, India. Results: In COVID-19 patients, particularly those with severe disease, had increased levels of IL-2 or IL-2R. Given IL-2's supportive role in the expansion and differentiation of T cells, the authors exhibiting that lymphopenia, particularly in severe COVID-19, could be attributed to nonfunctional and dysfunctional differentiation of CD4+ and CD8+ T cells as a result of low CD28 immuno-molecule expression on naive T cells. Conclusions: The literature review found that independent, early immunological prognostic markers for a poor prognosis, in addition to higher levels of IL-6, include a substantial proportion of large inflammatory monocytes and a small proportion of chronic CD28+ CD4+T cells. The current findings suggest that a combination of COVID-19 vaccination with SARS CoV-2-reactive naive T cells with the CD28 immune-molecule may be a viable method for establishing T-cell-based, adaptive cellular immunotherapy against COVID-19 infection. Further research is needed, especially larger studies to confirm the current findings, to improve early clinical treatment.

Validation of the STARZ neonatal acute kidney injury risk stratification score in an independent prospective cohort.

OBJECTIVE: A rapid AKI risk assessment score would allow for improving management and outcomes. STARZ (Sethi, Tibrewal, Agrawal, Raina, waZir) score was developed for acute kidney injury (AKI) risk stratification of critically ill neonates. This is the first independent validation for the novel score outside the original enrolled centres. STUDY DESIGN: 750 neonates were included in the study. The STARZ score was calculated after 12 hours of admission. Neonates admitted in NICU and receiving IV fluids for at least 48 hours were included. RESULTS: A total of 8.8% neonates had AKI in the first 7 days post admission. The duration of hospital stay was significantly higher among neonates with AKI [10.5 (7-19) vs. 7 (5-10) days; p < 0.001]. Mortality risk was 6.4 times higher among those with AKI [8 (12.1%) vs. 13 (1.9%); p < 0.001; RR (95% CI): 6.38 (2.74-14.83)]. In this study, the STARZ neonatal scoring model showed a sensitivity of 89.4% in detecting AKI with a 90.9% specificity and a high negative predictive value of 98.9%. The area under ROC was 0.958 (0.934-0981) - a high discriminative power. CONCLUSIONS: The STARZ score allows for AKI risk stratification, providing opportunity for therapeutic interventions which may improve outcomes in critically ill neonates.

A Review on Delivery and Bioavailability Enhancement Strategies of Azithromycin.

Azithromycin (AZI) belongs to the class of macrolide antibiotics that has limited water solubility and belongs to Biopharmaceutical Classification System Class II. Dissolution is the rate-limiting step in the absorption process of AZI. Several approaches have been investigated for enhancing the bioavailability of poorly soluble drugs. This review intends to explore the various strategies that have been investigated for improving the solubility and/or bioavailability of AZI and the delivery systems that have been designed for delivery of AZI in ocular fluid.

Towards the discovery of potential RdRp inhibitors for the treatment of COVID-19: structure guided virtual screening, computational ADME and molecular dynamics study.

Coronavirus disease 2019 (COVID-19) has become a major challenge affecting almost every corner of the world, with more than five million deaths worldwide. Despite several efforts, no drug or vaccine has shown the potential to check the ever-mutating SARS-COV-2. The emergence of novel variants is a major concern increasing the need for the discovery of novel therapeutics for the management of this pandemic. Out of several potential drug targets such as S protein, human ACE2, TMPRSS2 (transmembrane protease serine 2), 3CLpro, RdRp, and PLpro (papain-like protease), RNA-dependent RNA polymerase (RdRP) is a vital enzyme for viral RNA replication in the mammalian host cell and is one of the legitimate targets for the development of therapeutics against this disease. In this study, we have performed structure-based virtual screening to identify potential hit compounds against RdRp using molecular docking of a commercially available small molecule library of structurally diverse and drug-like molecules. Since non-optimal ADME properties create hurdles in the clinical development of drugs, we performed detailed in silico ADMET prediction to facilitate the selection of compounds for further studies. The results from the ADMET study indicated that most of the hit compounds had optimal properties. Moreover, to explore the conformational dynamics of protein-ligand interaction, we have performed an atomistic molecular dynamics simulation which indicated a stable interaction throughout the simulation period. We believe that the current findings may assist in the discovery of drug candidates against SARS-CoV-2.

Risk factors and outcomes of neonates with acute kidney injury needing peritoneal dialysis: Results from the prospective TINKER (The Indian PCRRT-ICONIC Neonatal Kidney Educational Registry) study.

BACKGROUND: Acute kidney injury (AKI) is common in neonates admitted to neonatal intensive care units (NICUs). There is a need to have prospective data on the risk factors and outcomes of acute peritoneal dialysis (PD) in neonates. The use of kidney replacement therapy in this population compared to older populations has been associated with worse outcomes (mortality rates 17-24%) along with a longer stay in the NICU and/or hospital. METHODS: The following multicentre, prospective study was derived from the TINKER (The Indian PCRRT-ICONIC Neonatal Kidney Educational Registry) database, assessing all admitted neonates ≤28 days who received intravenous fluids for at least 48 h. The following neonates were excluded: death within 48 h, presence of any lethal chromosomal anomaly, requirement of congenital heart surgery within the first 7 days of life and those receiving only routine care in nursery. Demographic data (maternal and neonatal) and daily clinical and laboratory parameters were recorded. AKI was defined according to the Neonatal Kidney Disease: Improving Global Outcomes criteria. RESULTS: Of the included 1600 neonates, a total of 491 (30.7%) had AKI. Of these 491 neonates with AKI, 44 (9%) required PD. Among neonates with AKI, the odds of needing PD was significantly higher among those with significant cardiac disease (odds ratio (95% confidence interval): 4.95 (2.39-10.27); p < 0.001), inotropes usage (4.77 (1.98-11.51); p < 0.001), severe peripartum event (4.37 (1.31-14.57); p = 0.02), requirement of respiratory support in NICU (4.17 (1.00-17.59); p = 0.04), necrotising enterocolitis (3.96 (1.21-13.02); p = 0.03), any grade of intraventricular haemorrhage (3.71 (1.63-8.45); p = 0.001), evidence of fluid overload during the first 12 h in NICU (3.69 (1.27-10.70); p = 0.02) and requirement of resuscitation in the delivery room (2.72 (1.45-5.12); p = 0.001). AKI neonates with PD as compared to those without PD had a significantly lower median (interquartile range) duration of stay in NICU (7 (4-14) vs. 11 (6-21) days; p = 0.004), but significantly higher mortality (31 (70.5%) vs. 50 (3.2%); p < 0.001). This discrepancy is likely attributable to the critical state of the neonates with AKI. CONCLUSIONS: This is the largest prospective, multicentre study specifically looking at neonatal AKI and need for dialysis in neonates. AKI was seen in 30.7% of neonates (with the need for acute PD in 9% of the AKI group). The odds of needing acute PD were significantly higher among those with significant cardiac disease, inotropes usage, severe peripartum event, requirement of respiratory support in NICU, necrotising enterocolitis, any grade of intraventricular haemorrhage, evidence of fluid overload more than 10% during the first 12 h in NICU and requirement of resuscitation in the delivery room. AKI neonates with PD as compared to AKI neonates without PD had a significantly higher mortality. There is a need to keep a vigilant watch in neonates with risk factors for the development of AKI and need for PD.

The effect of norepinephrine on clinical and hemodynamic parameters in neonates with shock: a retrospective cohort study.

There is limited data on the cardiovascular effects of norepinephrine (NE) in neonates. Our objective was to describe the clinical responses in neonates treated with NE infusion. This retrospective cohort study included neonates with evidence of shock and those who received NE infusion. PRIMARY OUTCOME: changes in mean blood pressure (MBP) at 6, 12, and 24 h post-initiation of NE. SECONDARY OUTCOMES: Changes in (i) diastolic BP, systolic BP, and vasoactive inotrope score (VIS) at 6, 12, and 24 h, (ii) urine output after initiation of NE ii) pH, lactate, fraction of inspired oxygen (FiO2) after initiation of NE, and (iv) adverse outcomes. Fifty infants received NE with mean (SD) gestational age of 34.3 (4.3) weeks and a mean birth weight of 2215 (911) g. Treatment began at a median age of 36 (IQR: 15.2, 67.2) hours of life and lasted 30.5 (IQR: 12.7, 58) hours. MBP improved from 34.4 mm Hg (SD: 6.6) at baseline to 39.4 mm Hg (SD: 10.5, p < 0.001) at 6 h, to 39.6 mm Hg (SD: 12.1, p = 0.002) at 12 h and to 40.4 mm Hg (SD: 15.5, p = 0.004) at 24 h after NE initiation. Vasoactive inotrope score declined from 30 (20, 32) to 10 (4, 30; p < 0.001) at 24 h. Urine output improved within 24 h [1.5 ml/kg/h (0.5, 2.3) at baseline to 3 (1.9, 4.3) at 24 h; p = 0.04]. Oxygen requirement decreased after NE initiation. CONCLUSION: The use of NE appears to be effective and safe for treating systemic hypotension in neonates. TRIAL REGISTRATION: Being a retrospective study, trial registration was not considered. WHAT IS KNOWN: • Dopamine has traditionally been used as the initial agent for treatment of neonatal hypotension. • Norepinephrine has recently been recommended as the first-choice vasopressor agent to correct hypotension in adults and pediatric patients, with insufficient data on the cardiovascular effects of NE in neonates What is new: • Mean blood pressure improved significantly at 6, 12, and 24 h with reduction in vasoactive infusion score at 12 and 24 h after norepinephrine infusion. • No significant change in heart rate or abnormal abdominal adverse effects noted in this study.

Validation of the STARZ neonatal acute kidney injury risk stratification score.

BACKGROUND: Neonatal acute kidney injury (AKI) is common in neonatal intensive care units (NICU) and leads to worse outcomes. Stratifying neonates into an "at risk" category allows health care providers to objectively recognize opportunities for improvements in quality of care. METHODS: The "Neonatal AKI Risk Prediction Scoring" was devised as the "STARZ [Sethi, Tibrewal, Agrawal, Raina, waZir]" Score. The STARZ score was derived from our prior multicentre study analysing risk factors for AKI in neonates admitted to the NICU. This tool includes 10 variables with a total score ranging from 0 to 100 and a cut-off score of 31.5. In the present study, the scoring model has been validated in our multicentre cohort of 744 neonates. RESULTS: In the validation cohort, this scoring model had sensitivity of 82.1%, specificity 91.7%, positive predictive value 81.2%, negative predictive value 92.2% and accuracy 88.8%. Based on the STARZ cut-off score of ≥ 31.5, an area under the receiver operating characteristic (ROC) curve was observed to be 0.932 (95% CI, 0.910-0.954; p < 0.001) signifying that the discriminative power was high. In the validation cohort, the probability of AKI was less than 20% for scores up to 32, 20-40% for scores between 33 and 36, 40-60% for scores between 37 and 43, 60-80% for scores between 44 and 49, and ≥ 80% for scores ≥ 50. CONCLUSIONS: To promote the survival of susceptible neonates, early detection and prompt interventional measures based on highly evidenced research is vital. The risk of AKI in admitted neonates can be quantitatively determined by the rapid STARZ scoring system. A higher resolution version of the Graphical abstract is available as Supplementary information.

Solubility enhancementofcefixime trihydrate by solid dispersions using hydrotropic solubilization technique and their characterization

Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.

Multisystem inflammatory syndrome in a neonate masquerading as surgical abdomen.

Worldwide, thousands of cases of multisystem inflammatory syndrome in children (MIS-C) have already been reported in children. Evidence regarding neonatal MIS-C is limited. We present the first case report of a neonate presenting within 48 hours of life with predominant abdominal signs mimicking surgical abdomen. Clinical picture comprised fever, multiorgan dysfunction (gastrointestinal, cardiorespiratory, hepatic and dermatological), positive inflammatory markers, high ferritin and high D-dimer levels. Cardiac enzyme N-terminal-pro-B-type natriuretic peptide as well as D-dimer levels were elevated. Blood, urine, stool and cerebrospinal fluid cultures were sterile. Positive anti-SARS-CoV-2 IgG in both the mother and the infant, along with an epidemiological evidence of maternal contact with COVID-19, clinched the diagnosis of MIS-C. Immunomodulatory drugs (intravenous immunoglobulin and systemic steroids) were administered and showed good clinical response. A high index of suspicion of MIS-C in critically ill neonates can improve outcomes.

Incidence, Risk Factors, and Outcomes of Neonatal Acute Kidney Injury: Protocol of a Multicentric Prospective Cohort Study [The Indian Iconic Neonatal Kidney Educational Registry].

Background: Acute kidney injury (AKI) is a significant problem in neonates, but the evidence is sparse. Neonatal AKI is an independent risk factor for increased mortality and prolonged hospital stay. There are stark differences in the epidemiology of AKI in neonates amongst the developing and the developed world. Increased prevalence of neonatal sepsis, lack of awareness about neonatal AKI and poor access to pediatric nephrologists add to the improper management of neonatal AKI in the developing countries. Methods: This study is a multicentric, national, prospective cohort study [The Indian iconic Neonatal Kidney Educational Registry (TINKER)] conducted in level 2-3 NICUs in 11 centers across India. We have enrolled nearly 2,000 neonates over the study period. Neonates (≤ 28 days) who were admitted in NICU and those who received intravenous (IV) fluids for at least 48 h for hydration and/or nutrition have been included. Data collection included: (1) baseline demographics (2) daily physiologic and laboratory parameters (3) discharge data. KDIGO workgroup AKI definition modified for neonates was used for defining AKI. Data entry was carried out by individual participating centers using a web-based database (akiregistry.org). De-identified data has been maintained and handled by the principal investigator (PI). This collaboration plans to disseminate data through peer-reviewed publications and through presentations at educational conferences. Conclusions: The purpose of this study is to create the first prospective neonatal all-cause AKI data repository and describe the incidence of neonatal AKI in NICUs in the country and determine the risk factors as well as the outcomes of such neonates-both short-term and long-term outcomes. This will eventually spur therapeutic advancements, facilitate decipherment of epidemiological trends, risk factors as well as outcomes and identify disparities in management across the nation.

Solid Dispersion: A Mechanistic and Realistic Approach on Antihypertensive Drug as a Drug Carrier System.

A major percentage of the new chemical entities are reported to have poor aqueous solubility. Several antihypertensive drugs used clinically have either low solubility or high hepatic metabolism, thereby presenting low bioavailability (BA) and high pharmacokinetic variability. Improving the aqueous solubility of drug molecules would assist in overcoming the variability, and several approaches for improving solubility have been reported. Solid dispersion (SD) is known as a potential technique to conquer the problem of poor aqueous solubility and low BA. Drug solubility is improved by increasing the wetting property of drugs. This review is focused on discussing various approaches to improve solubility, classification, and different approaches used for formulation of SDs, along with special emphasis on the application of the SD approach for improving solubility and eventually enhancing dissolution and increasing the BA of antihypertensive drugs. The review leads to the conclusion that the use of more than one polymeric carrier for formulating SDs might help in overcoming storage and stability issues and in increasing the commercial viability and success of SDs.

Fetal oxidative stress, micronutrient deficiency and risk of retinopathy of prematurity: a nested case-control study.

We hypothesized that fetal oxidative stress and micronutrient deficiencies contribute to higher incidence of retinopathy of prematurity (ROP) in developing countries. In a nested case-control study, preterm infants (< 37 weeks, < 1700 g) were included at birth and followed until 40 weeks post-menstrual age (PMA). Maternal, cord, and neonatal serum/plasma samples at 40 weeks PMA were frozen. Samples of "cases" with ROP and gestational age (GA) and birth weight-matched "controls" with no ROP (in 1:4 ratio) were thawed and analyzed. PRIMARY OUTCOME: MDA concentration in cord plasma. SECONDARY OUTCOMES: MDA in maternal and 40-week PMA plasma; copper, zinc, and vitamin A in maternal, cord, and 40-week PMA samples. Thirty-eight cases and 151 controls had a mean (SD) GA of 29.5 (1) and 29.9 (1) weeks respectively. Following were associated with ROP: higher MDA concentration in cord and 40-week PMA samples; lower copper and zinc in maternal serum; lower zinc and vitamin A in cord sample (all p < 0.05). MDA [adjusted OR (aOR) = 4.13 (95% CI 1.83-9.27)] and vitamin A [aOR = 0.09 (95% CI 0.02-0.4)] concentration in cord plasma and weight gain (g/kg/week) [aOR = 0.97 (0.95-0.99)] independently predicted ROP. CONCLUSION: Increased oxidative stress and deficiency of micronutrients from fetal life were associated with ROP. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/REF/2014/12/008174. What is Known: • In developing countries, there is a higher incidence of retinopathy of prematurity (ROP), but micronutrient deficiencies have not been adequately investigated as risk factors. • Few observational studies have shown an association between ROP and postnatal increase in malondialdehyde (MDA) levels and deficiencies of antioxidant vitamins and minerals, but none in cord blood. What is New: • High MDA, low zinc, and low vitamin A levels in cord blood and low copper and zinc levels in maternal blood are associated with the development of ROP. • On multivariable analysis, high cord blood MDA and low cord blood vitamin A are independent predictors of ROP.

Surfactant dysfunction disorder masquerading as meconium aspiration syndrome and persistent pulmonary hypertension of the newborn.

About 10% of term neonates present with respiratory distress at birth. The most common aetiologies include transient tachypnoea of the newborn, pneumonia and meconium aspiration syndrome (MAS). Hyaline membrane disease (HMD) in a term infant occurs either as primary HMD, secondary surfactant deficiency or congenital surfactant dysfunction. A detailed history supported with appropriate radiological and laboratory investigations can help a clinician reach a diagnosis. We report a case of surfactant dysfunction disorder which presented as severe MAS and persistent pulmonary hypertension of the newborn. In the infant described, the significant history of a sibling death with severe neonatal respiratory disease led us to think of diffuse developmental lung diseases especially surfactant dysfunction syndromes. Exome sequencing detected a heterozygous missense variation in exon 21 of the ATP binding cassette protein member 3 (ABCA3) gene. Based on the clinical picture supported with the exome sequencing, a diagnosis of surfactant dysfunction disorder (ABCA3 deficiency) was confirmed.

A comparative evaluation of portable Doppler ultrasound versus electrocardiogram in heart-rate accuracy and acquisition time immediately after delivery: a multicenter observational study.

BACKGROUND: The assessment of newborns' heart rate (HR) in the delivery room is one of the important steps to ascertain the need for initiation and continuation of resuscitation. At present, ECG is the "gold standard" to monitor neonatal HR in the delivery room. However, various limitations with the use of ECG exist. Furthermore, in developing countries, ECG may not be universally available in delivery rooms. OBJECTIVE: To compare the accuracy and HR acquisition time of portable Doppler ultrasound (PDU) versus electrocardiogram (ECG) in newborns. METHODS: This multicenter, prospective, observational study across five centers in India between January and September 2017 included neonates more than 34 weeks of gestation (n = 131) delivered by cesarean section. The accuracy of HR recorded by PDU (HRPDU) versus that by ECG (HRECG) was the primary outcome. Secondary outcomes included time to acquisition of an audible and/or visible signal and device application. RESULTS: Mean (±SD) gestational age and birthweight were 37.7 (±1.2) weeks and 2954 (±457) g, respectively. The mean (±SD) visible HRPDU was 158 (±21) bpm versus HRECG of 161.3 (±20) bpm (p = .07) which were comparable. The median (1st, third quartile) time to acquisition of audible HRPDU (76 [51, 91] s), was significantly shorter than that of HRECG (96.5 [74.2, 118] s; p < .001). CONCLUSION: Portable Doppler has similar accuracy to ECG and is faster in acquiring the signal.

Impact of COVID-19 on Nephrology Patients: A Mechanistic Outlook for Pathogenesis of Acute Kidney Injury.

CONTEXT: Some research has indicated that SARS-CoV-2 has had effects on the various functions of the renal system. Acute kidney injury (AKI) is a dangerous and broadly spread pathological illness. OBJECTIVE: In this review, we emphasize that AKI can be a severe complication of COVID-19 and highlight the importance of assessing, defining, and reporting the course of AKI. DESIGN: The research team performed a literature review, searching relevant literature databases. We searched four databases, PubMed, EMBASE, Web of Science and CNKI (Chinese Database), to identify studies reporting COVID-19. Articles published on or before May 10, 2020 were eligible for inclusion. We used the following search terms: "Coronavirus" or "2019-nCoV" or "COVID-19" or "AKI" or "renal failure" or "nephrology". SETTING: This study was take place at Jouf University, Sakaka, Al-Jouf, Saudi Arabia. RESULTS: The review showed that AKI patients, who were susceptible to a cytokine storm, showed clinical deterioration. This result allowed the current research team to develop a hypothesis of a set of adverse events in COVID-19 that proposes the modification of inflammatory pathways by stimulation of nAChRα7. The stimulation could occur by way of IL-6 / JAK2 / STAT3 / SOCS3 and NF-κB (p65)/IL-18, which work together to induce AKI and increase overall renal-related diagnostic markers, such as plasma creatinine and tubular cell damage. In addition, the functioning of the cholinergic anti-inflammatory pathway may be determined by nicotine. Pharmacological nicotine products are widely available, and their role in COVID-19-mediated AKI can be further evaluated. CONCLUSIONS: The research team concluded that the dysregulation of the cholinergic anti-inflammatory system could explain most of the clinical features of severe COVID-19.

Neonatal lupus erythematosus presenting with rash, thrombocytopenia compounded by cytomegalovirus colonisation: a diagnostic dilemma.

Neonatal lupus erythematosus (NLE) should be considered when a newborn develops atrioventricular heart block along with the presence of autoantibodies to Sjogren's syndrome autoantigens in the maternal serum. NLE can also present with features such as cutaneous lesions, hepatic dysfunction or haematological abnormalities. Differential diagnosis usually includes congenital infections as there is a significant overlap of symptoms with NLE. We report a case of NLE who had multiorgan involvement with macular erythematous skin lesions present at birth, and on investigation was found to have cytomegalovirus (CMV) infection. The diagnostic dilemma was whether to consider this infection as symptomatic or just colonisation. In the infant described, the absence of end organ damage specific to CMV infection (hearing loss, intracranial calcifications, retinitis, brain involvement) made a diagnosis of symptomatic CMV unlikely.