Adjuvant therapy in neonatal sepsis to prevent mortality - A systematic review and network meta-analysis.

BACKGROUND: Despite appropriate antibiotic therapy, the risk of mortality in neonatal sepsis still remains high. We conducted a systematic review to comprehensively evaluate different adjuvant therapies in neonatal sepsis in a network meta-analysis. METHODS: We included randomized controlled trials (RCTs) and quasi-RCTs that evaluated adjuvant therapies in neonatal sepsis. Neonates of all gestational and postnatal ages, who were diagnosed with sepsis based on blood culture or sepsis screen were included. We searched MEDLINE, CENTRAL, EMBASE and CINAHL until 12th April 2021 and reference lists. Data extraction and risk of bias assessment were performed in duplicate. A network meta-analysis with bayesian random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. RESULTS: We included 45 studies involving 6,566 neonates. Moderate CoE showed IVIG [Relative Risk (RR); 95% Credible Interval (CrI): 1.00; (0.67-1.53)] as an adjunctive therapy probably does not reduce all-cause mortality before discharge, compared to standard care. Melatonin [0.12 (0-0.08)] and granulocyte transfusion [0.39 (0.19-0.76)] may reduce mortality before discharge, but CoE is very low. The evidence is also very uncertain regarding other adjunctive therapies to reduce mortality before discharge. Pentoxifylline may decrease the duration of hospital stay [Mean difference; 95% CrI: -7.48 days (-14.50-0.37)], but CoE is very low. CONCLUSION: Given the biological plausibility for possible efficacy of these adjuvant therapies and that the CoE from the available trials is very low to low except for IVIG, we need large adequately powered RCTs to evaluate these therapies in sepsis in neonates.

Bedside sonography performed by neonatology residents to confirm central vascular catheter position in neonates - A Prospective Diagnostic Evaluation study.

OBJECTIVE: To evaluate the diagnostic accuracy and utility of bedside ultrasound (US) by neonatology residents to confirm position of umbilical venous catheter (UVC), umbilical arterial catheter (UAC), and peripherally inserted central catheter (PICC). METHODS: In this prospective study, we included neonates who required UVC, UAC or PICC insertion. Two neonatology residents performed all bedside US examinations after a short period of training. Plain radiograph was taken as gold standard. Time taken for confirmation of catheter position by US and radiograph was recorded. RESULTS: We recruited 71 neonates for UVC and UAC, and 40 neonates for PICC. Sensitivity and specificity of US in identifying a malpositioned catheter was good for UVC (94% and 66.7% respectively) and UAC (86.7% and 94.5%). Agreement between radiograph and US was good for UVC [0.718 (0.512, 0.861); p < 0.001] and UAC [0.857 (0.682, 0.953); p < 0.001]. Sensitivity (47.8%) of US in identifying a malpositioned PICC was low, though specificity (82.4%) was good. Agreement between radiograph and US in identifying PICC position was poor [0.25 (-0.084, 0.545); p 0.024]. This was due to incorrect interpretation of catheter position on radiograph in some infants, which was confirmed by the radiologist. The median time taken for US was significantly less than time taken for radiograph in confirming the position of UVC (50 vs. 155 minutes; p < 0.001)), UAC (45 vs. 128 minutes; p < 0.001), and PICC (60 vs. 136 minutes; p < 0.001). CONCLUSION: US examination byneonatology residents has good diagnostic accuracy in confirming the position of UAC and UVC, and possibly PICC in neonates. The time taken to confirm catheter position by US is significantly less than radiograph.

Troponin-T as a biomarker in neonates with perinatal asphyxia.

BACKGROUND: Troponin-T is a commonly used cardiac biomarker, which could be useful in perinatal asphyxia. We aimed to analyze troponin-T concentrations in asphyxiated neonates and to correlate the concentrations with clinical outcomes. METHODS: Data were collected from electronic medical records of neonates diagnosed with perinatal asphyxia over a period of four years. RESULTS: There were 63 neonates with moderate to severe encephalopathy, in whom serial troponin-T concentrations had been done on days 1, 3, and 7. 53 (84%) asphyxiated infants had troponin-T concentration >100 pg/ml at 2-4 h of life.The difference in troponin-T concentrations between moderate and severe encephalopathy was not statistically significant (173 vs. 263 pg/ml, p value 0.40). The difference in the concentrations at 72 hours between cooled and non-cooled neonates was not significant (48.5 vs. 62.5 pg/ml, p value 0.22). Troponin-T concentration was significantly higher in babies with hypotensive shock and hepatic injury, but not acute kidney injury. There was no significant correlation between troponin-T and the extent of resuscitation needed.Troponin-T concentration on day 1 of life was significantly higher in babies who died than who survived (407 vs. 168 pg/ml, p value 0.03). ROC curve for troponin-T to predict mortality had an area under the curve (AUC) of 0.803; the best cut-off value (190 pg/ml) had 82% sensitivity and 80% specificity. CONCLUSION: There was no significant difference in troponin-T concentrations between cooled and non-cooled neonates. Troponin-T concentration had a good predictive accuracy for mortality before discharge.

Utility of neutrophil volume conductivity scatter (VCS) parameter changes as sepsis screen in neonates.

OBJECTIVE: The objective of this study was to determine changes in neutrophil volume conductivity scatter (VCS) parameters and their distribution widths (DW) in neonatal sepsis and to estimate their optimal cutoff levels using receiver operating characteristic (ROC) curves. STUDY DESIGN: In a cohort of neonates evaluated for sepsis, blood counts and blood culture were performed initially, with repeat counts and C-reactive protein (CRP) done after 24 to 48 h. Neutrophil VCS parameters from both the initial and repeat blood counts were analyzed. Babies were classified as having blood culture-positive sepsis, probable sepsis (clinical course consistent with sepsis and CRP-positive, but culture-negative) and no sepsis (clinical course not compatible with sepsis, culture- and CRP-negative). RESULTS: A total of 600 babies were included: 240 (40%) babies in the sepsis group and 360 (60%) babies in the control group. All the neutrophil VCS parameters and their DWs (except for low angle light scatter in the repeat counts) were significantly different between the two groups, with an area under curve in the ROC curve of >0.6 for most parameters. The five most significant VCS parameters (mean neutrophil volume (MNV), median angle light scatter (MALS), lower median angle light scatter (LMALS), MNV-DW and ALL-DW) had around 65 to 75% sensitivity and specificity. A combination of leukopenia, thrombocytopenia, MNV and LMALS had a likelihood ratio (LR)+ of 15.3 and LR- of 0.17. With a pre-test probability of 40%, post-test probability increased to 91% for a positive test and decreased to 10% for a negative test. A prospective validation study was performed recruiting an additional 60 babies, which showed similar results, assuring that the cutoffs were robust. CONCLUSION: Neutrophil VCS parameters cannot be considered as stand-alone tests to diagnose or rule out neonatal sepsis, but can be used in combination with other hematological screening tests to improve the diagnostic accuracy of the neonatal sepsis screen.

Appendicular Perforation in a Neonate Masquerading as Testicular Torsion.

BACKGROUND: Neonatal appendicitis is difficult to diagnose, and is associated with high mortality. CASE CHARACTERISTICS: A preterm (33 wk) neonate developed abdominal distension feeding intolerance and erythema of left inguinal region on day 4 of life. OBSERVATION: Testicular torsion was suspected but inguinal exploration revealed normal testis with feco-purulent fluid draining into processus vaginalis from peritoneal cavity. Laparotomy revealed inflamed and perforated appendix. Appendectomy and intravenous antibiotics led to a recovery. MESSAGE: Appendicitis in a neonate can rarely present with inguinal symptoms, masquerading as testicular torsion.

A report of an Indian boy with a delayed diagnosis of pseudochondroplasia.

THE MUTATIONS IN THE CARTILAGE OLIGOMERIC MATRIX PROTEIN (COMP) GENE ARE ASSOCIATED TWO COMMON AND ALLELIC BONY DYSPLASIAS: Psuedoachondroplasia (PSACH) and Multiple epiphyseal dysplasias-1 (MED-1). The characteristic radiological features of both has been well established in the literature, with areas of overlap between the two in certain forms of mild PSACH and severe MED. MED is also a genotypically and a phenotypically heterogeneous disease. Here, we emphasise the salient radiological features which aid in the diagnosis of PSACH and COMP MED; which may enable a targeted molecular analysis.