Utility of the Growth Differentiation Factor-15 in the Differential Diagnosis of Follicular-Patterned Lesions of the Thyroid on Cytopathologic and Histopathologic Samples.

Background Follicular-patterned lesions are a major gray zone in thyroid cytopathology. The recently introduced 2022 World Health Organization (WHO) classification emphasizes the importance of genetic alterations in thyroid neoplasms with the introduction of certain newer terminologies that are expected to cause remarkable changes in cytopathologic and histopathologic reporting. Although molecular assays such as the Afirma gene expression classifier and the ThyroSeq are already in use, there has been an ongoing search for further reliable molecular markers. The growth differentiation factor-15 (GDF-15) is one among them. This study aimed to determine the diagnostic utility of GDF-15 mRNA expression in frozen tissue and fine-needle aspiration (FNA) samples from follicular-patterned thyroid lesions and neoplasms. Methodology The real-time quantitative polymerase chain reaction was performed on 75 frozen tissue and FNA samples each from 19 cases of follicular thyroid hyperplasia (FTH), 10 nodular goiters (NGs), 17 follicular thyroid adenomas (FTAs), eight follicular thyroid carcinomas (FTCs), 12 follicular variant of papillary thyroid carcinomas (FVPTCs), and nine classic papillary thyroid carcinomas (CPTCs) that were diagnosed according to the 2017 WHO classification of thyroid neoplasms. The GDF-15 mRNA expression in all these cases was assessed and compared with the control thyroid tissue samples. One-way analysis of variance and the Kruskal-Wallis test were performed using GraphPad Prism 8 software to determine the significance of differences in the GDF-15 mRNA levels among various thyroid lesions. Results A higher GDF-15 mRNA expression was noted in the malignant thyroid neoplasms including FTC, FVPTC, and CPTC in comparison to FTA, with a fold change between the malignant and benign groups being more than 244.18 times. A difference in the fold change was noted between FTH and FTA with an increase in GDF-15 mRNA level in the latter, which was statistically not significant. Conclusions The fact that GDF-15 mRNA was studied both on fine-needle aspiration cytologic and the frozen tissue material and that the majority of the lesions studied were follicular-patterned establishes the GDF-15 as a potential marker not only for diagnosing malignant thyroid neoplasms of the follicular epithelium but also in distinguishing benign and malignant follicular-patterned neoplasms of the thyroid.

Myocardial Bridging in Cases of Sudden Death and its Association with Clinicopathologic Characteristics.

Background: Myocardial bridging (MB) is the course of the epicardial segment of a coronary artery within the myocardium. The systolic compression of this segment called the tunneled segment may lead to alterations in blood flow to the heart. We have studied the gross and microscopic features of MB in cases of sudden cardiac death and analyzed its characteristics and whether there is any association with other clinicopathological characteristics which may help us to understand the pathogenesis and risk stratification. Materials and Methods: This is a retrospective descriptive study of 132 postmortem heart specimens of sudden cardiac death. The coronary arteries were dissected, and MB and its characteristics were studied. Statistical analysis was performed using the Chi-square and Fisher's exact tests (P < 0.05 significant). Results: MB was present in 28 cases (21.2%), with a mean age of 49.5 years and male:female ratio of 27:1. MB was seen in the left anterior descending artery in 86.2% of cases, the right coronary artery in 10%, and left circumflex artery in 3.5% of cases. Atherosclerosis was seen in the segment proximal to the tunneling in 89.2% of cases leading to infarction in four cases. Left ventricular hypertrophy (LVH) was significantly associated with MB cases (19/68%) (P < 0.05). Conclusion: MB causes turbulence of blood in the proximal segment leading to coronary atherosclerosis, thereby predisposing the heart to ischemic changes and LVH and may lead to infarction in a few cases.

Successful Implementation of Single Urine Polymerase Chain Reaction Test for Evaluating Suspected Cytomegalovirus Infection in Neonates.

Overuse of laboratory investigations is viewed as medical waste. In the past, to diagnose congenital cytomegalovirus (CMV) infection, consecutive urine culture samples were obtained. With the advent of polymerase chain reaction (PCR) technology, 1 urine specimen should be enough. We conducted this quality improvement study to look at the effect of a practice change from 3 to 1 urine specimen for PCR testing. Methods: The authors instituted a single PCR urine test for CMV in their neonatal intensive care unit (NICU) in May 2021. We reviewed the data on all the urine CMV PCRs obtained on neonates for 1 year, May 1, 2020, to April 30, 2021 (Epoch 1), and compared it with the data obtained from May 1, 2021, to February 28, 2022 (Epoch 2). Results: A total of 3,612 neonates were born during the study period-1,816 infants were born during Epoch 1 and 1,796 infants during Epoch 2. A total of 97 neonates (5.3%) were evaluated for congenital CMV infection during Epoch 1 and 149 infants (8.2%) during Epoch 2. The single urine sample CMV evaluation rate during Epoch 1 was 53.6% (52 infants out of 97 infants evaluated), which increased to 98.6% in Epoch 2 (147 infants out of 149 infants), P < 0.001. The monthly average cost per infant declined from a mean value of 70.1 dollars to a mean value of 39.5 dollars. Conclusions: We increased the single specimen urine CMV PCR test from 53.6% to 98.6%. The intervention resulted in reducing waste and improving resource utilization.

Feasibility of handheld ultrasound to assess heart rate in newborn nursery.

BACKGROUND AND OBJECTIVES: Heart rate (HR) assessment is important during neonatal resuscitation. The most reliable ways of assessing HR at birth are pulse oximetry (PO) and/or electrocardiograph (ECG). However, delayed recording time due to poor perfusion or probe and electrode placement has been a concern. Point-of-care ultrasound (POCUS) provides a real-time instant view of the heart. The aim of this study was to look at the feasibility of POCUS in assessing the heart rate of stable, healthy, term neonates. METHODS: The study was approved by the institutional review board, and informed consent was obtained from the subject's mother. A real-time video image was obtained from the POCUS probe using the app on the smartphone. The principal investigator (PI) counted the heart beats for six seconds using a stopwatch, which was then multiplied by 10 to give the HR per minute. The assistant recorded the simultaneous HR using the PO. The HRs obtained from both methods were recorded and then compared using the Pearson correlation and Bland-Altman plot. RESULTS: A total of 30 HR observations were made using the POCUS and PO simultaneously. The correlation coefficient (r) was noted to be 0.75 with a p-value of <0.0001 for pairwise correlation. A strong agreement was noted between the two methods using Bland-Altman Plot. CONCLUSION: We were able to demonstrate the feasibility of using handheld POCUS in assessing the HR of stable NB infants in the newborn nursery. A follow-up study is planned to evaluate its feasibility in the delivery room.

Neonatal Myocardial Ischemia-Reperfusion Injury: A Proposed Pathogenic Sequence in the Context of Maternal/Fetal Vascular Malperfusion and Paradoxical Embolism.

BACKGROUND: Neonatal myocardial infarction (MI) in a structurally normal heart is frequently an obscure event that remains undiagnosed until autopsy. Causal attributions usually cite underlying maternal or fetal conditions. Refinement in understanding of pathogenic mechanisms underlying neonatal MI is key to advancements in diagnosis, prevention, treatments and prognosis. OBJECTIVE: This study presents a 36-week gestational age female with perinatal asphyxia, congenital hemolytic anemia and umbilical vein thrombosis who sustained catastrophic MI with reperfusion injury; and it reviews pertinent literature. RESULTS: We propose a pathogenic sequence that links maternal vascular malperfusion, fetal vascular malperfusion, hemolytic anemia, umbilical venous thrombosis, and paradoxical thromboemboli. CONCLUSION: This case highlights the importance of placental examination in connecting complex neonatal events with adverse maternal/placental conditions. A high index of suspicion is essential for early diagnosis of neonatal MI.

Metastatic adenocarcinoma presenting as monoarticular arthritis of the knee: A case report with review of literature.

Patients who develop metastatic arthritis secondary to solid tumors are rare. It is even more uncommon to be a presenting symptom. We present a case where a known case of osteoarthritic patient presented with complaints of knee swelling secondary to primary colonic carcinoma with lung metastasis. It was initially diagnosed on histopathology examination as metastatic adenocarcinoma from excised synovial mass and further investigated for primary carcinoma. Later, computed tomography was done and found out the primary colonic carcinoma arising from transverse colon along with lung metastasis.

Morphological Cardiac Alterations in Liver Cirrhosis: An Autopsy Study.

BACKGROUND: Cirrhosis can cause various cardiac complications and severely affect the prognosis of the patient suffering from cirrhosis. Anatomical, morphological variations in the heart of patients with liver cirrhosis in the absence of known cardiac disease has not been well described. There is a paucity of studies in the literature on cardiac alterations in cirrhosis. Early detection of known cardiac alterations can further help in improving the quality of life. MATERIALS AND METHODS: A cross-sectional descriptive study was conducted in the departments of pathology and forensic medicine of our institution. An autopsy-based prospective study of forty consecutive patients with final diagnosis of liver cirrhosis were included. Patients with a known history of cardiac disease/anomaly were excluded from the study. Macroscopic and microscopic changes in the heart and coronaries were noted and statistically analyzed. RESULTS: Analysis of the hearts on gross examination showed cardiomegaly in 31 patients (77.5%). All cases had left ventricular hypertrophy. Endocardial thickening was seen in 22 patients (55%). Calcified mitral valve was seen in 9 patients (22.5%).On microscopy, apart from hypertrophy, the pathological changes like interstitial oedema (47.5%), fibrosis (45%), cardiac muscle disarray (87.5%), fatty infiltrate (10%), pericarditis (5%), and severe coronary artery atherosclerosis (17.5%) were seen in the patients. CONCLUSION: Knowledge about the involvement of the heart in liver cirrhosis is essential for both the physician and the surgeons to prevent adverse outcomes during liver transplantation and can further help in improving the quality of life of the patient.

Bevacizumab for Retinopathy of Prematurity: 2-Year Neurodevelopmental Follow-up.

OBJECTIVE: This study aimed to determine whether infants who were treated with intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP) were at higher risk of death or neurodevelopmental impairment (NDI) when compared with infants who were not treated with IVB (Laser only). STUDY DESIGN: This retrospective study included 146 infants born from 2009 through 2016 with a birth weight (BW) <1,000 g, gestational age <27 weeks, and required ROP therapy. Death and NDI rates were assessed at 18 to 24 months' corrected age. RESULTS: Rates of death or severe NDI were 62 and 53% in the IVB (n = 61) and Laser only (n = 85) groups, respectively. This difference was not statistically different despite sample selection bias in treating growth-restricted infants with IVB, BW (median [IQR]) was 481 (420-583) versus 547 (473-640) g in IVB and Laser only groups, respectively, p = 0.003. The adjusted odds ratio and 95% confidence interval of death or severe NDI was 0.86 (0.33-2.20). CONCLUSION: Bevacizumab therapy for ROP did not affect survival and neurodevelopment of extremely preterm infants. KEY POINTS: · Intravitreal bevacizumab therapy for retinopathy of prematurity may be safe in periviable preterm infants.. · Intravitreal bevacizumab therapy does not increase mortality rate in periviable preterm infants.. · Intravitreal bevacizumab therapy does not increase adverse neurodevelopmental outcome in periviable infants..

A rare association of right hemicerebral dysgenesis with congenital anophthalmia in a neonate.

Congenital anophthalmia is rare and can occur due to various etiologies, including genetic defects, teratogenic exposures, and vascular disruptions. We report a rare case of right-sided congenital anophthalmia and hemicerebral dysgenesis in association with ipsilateral hemicerebral vascular dysgenesis in a neonate. Postnatal neuroimaging was conspicuous for a "bare orbit sign." A unilateral cranial neurocristopathy was suspected to be an underlying etiopathology for such a diffuse defect.

Implementation of a Modified Neonatal Early-onset Sepsis Calculator in Well-baby Nursery: a Quality Improvement Study.

BACKGROUND: The use of sepsis risk scores (SRSs), calculated based on the neonatal early-onset sepsis (EOS) calculator, has been shown to limit the unwarranted sepsis evaluations and to reduce the empirical use of antibiotics in neonates.s. PURPOSE: To reduce both the sepsis evaluation rate (SER) and antibiotic initiation rate (AIR) by 25% from baseline by incorporating conservative SRS cutoff values into the routine sepsis risk assessment of well-appearing neonates born at 34 weeks and older gestation. METHODS: During a pre quality improvement (QI) period (June 2016-August 2016), a QI team calculated SRS on all newborn infants to determine safe SRS cutoff values. During the QI-study period (September 2016-November 2017), we implemented an EOS evaluation algorithm based on 2 SRS cutoff values, 0.05 (later increased to 0.1) for sepsis evaluation and 0.3 for the initiation of antibiotic therapy. Monthly SER and AIR were summarized and analyzed by using standard statistical tests and statistical process control charts. During the surveillance phase (January 2019-June 2019), we evaluated whether previously attained improvements in SER and AIR were sustained. RESULTS: During the pre-QI period, the mean (±SD) of monthly SER and monthly AIR were 23.8% (±5.7%) and 6.2% (±0.4%), respectively. During the QI-study period, the mean (±SD) of monthly SER and monthly AIR decreased to 15% (±4.7%), P = 0.01, and 3.2% (±1.5%), P = 0.005, respectively. During the surveillance period, both outcome measures were comparable with the QI-study period. CONCLUSION: The implementation of a modified EOS calculator-based EOS algorithm using a conservative approach was successful in reducing antibiotic exposure and the need for blood work in well-appearing neonates.

Terbutaline-induced neonatal ventricular tachycardia: A case report and review of literature.

Neonatal ventricular tachycardia (VT) is an extremely rare condition. We present a 35-week-old gestation neonate who developed tachycardia following maternal exposure to terbutaline. Upon transfer to our neonatal intensive care unit, an electrocardiogram (ECG) was obtained which was consistent with VT. The arrhythmia did not respond to vagal maneuvers or adenosine but resolved following cardioversion demonstrated on postcoversion ECG. At outpatient follow-up, the infant had no further episodes of arrhythmia. To the best of our knowledge, this represents the first case describing terbutaline-induced fetal or neonatal VT.

A Comparative Study between Vedic and Contemporary Education Systems using Bio-Energy Markers.

BACKGROUND/AIM: "The destiny of the whole world depends on the children. If you want to see the silver lining on the horizon it is not you and me, but the children who have to be spiritualized" says Swami Satyananda Saraswati. Sri Aurobindo states "Education to be complete must have five principal aspects corresponding to the five principal activities of the human being: the physical, the vital, the mental, the psychic and the spiritual." Vedic education system (VES) focuses on inculcating all facets for overall development of personality. This study is an attempt to understand the lore of Vedic education followed by yoga as a way of lifestyle for physiological well-being and for successful unfoldment of children's personality. MATERIALS AND METHODS: The sample size was 378 (108 VES and 270 contemporary education system [CES]). We have excluded volunteers who had minor health problems from the study. The ethical clearance was taken from SVYASA University Ethics Committee, and informed consent was obtained for each individual undergoing the study. As it was aimed to collect one-time data, the yoga as a lifestyle in VES itself considered as an intervention. Thus, the two systems of educations are compared. The variables are measured using the Electro-photonic Image Bio-Well instrument. RESULTS: Bio-Well variables for VES and CES were compared. There was a significant difference in VES and CES energy level scores, left-right symmetry scores, organ balance, and entropy coefficient scores. CONCLUSIONS: Results suggest that Vedic Education System to be better in the measured parameters compared to Contemporary Education System.

Cytomorphometric Study of Changes in Buccal Mucosal Cells in Alcoholics.

BACKGROUND: Chronic alcohol consumption carries a high risk for oral and pharyngeal cancers among persons who have never smoked. Excessive alcohol consumption displays cytogenetic changes in oral mucosa cells. Cytomorphometric analysis of oral mucosal cells helps in the early detection of cytomorphological transformations in alcoholics before and after the onset of carcinoma. MATERIALS AND METHODS: A prospective, hospital-based, comparative study was done after written informed consent. Smears were obtained from the clinically normal buccal mucosa of 102 randomly selected alcoholic patients attending the medicine outpatient department aged above 25 years who consumed a minimum of 45 ml alcohol per day for at least 10 years and of 102 nonalcoholics as control. The slides were immediately fixed in absolute methanol and stained by the Papanicolaou (Pap) staining technique. PAP-stained smears were examined under the light microscope. Using the image J 1.47 image analysis software, a morphometric analysis of around 50 cells/case was done. RESULTS: A statistically significant increase in mean cytoplasmic area (P < 0.001), mean nuclear area (P < 0.01), and cell-to-nuclear parameter ratio (P < 0.001) was seen in the alcohol group in comparison with the control group. CONCLUSION: Prolonged consumption of alcohol produces cytomorphometric changes in buccal mucosal cells before the onset of premalignant lesions.

Correction to: A single-dose indomethacin prophylaxis for reducing perinatal brain injury in extremely low birth weight infants: a non-inferiority analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A single-dose indomethacin prophylaxis for reducing perinatal brain injury in extremely low birth weight infants: a non-inferiority analysis.

OBJECTIVE: To evaluate whether rates of perinatal brain injury among extremely low birth weight infants are comparable between two treatments: single-dose indomethacin prophylaxis (SGL-IP) (0.2 mg/kg, given once) vs. standard-dose indomethacin prophylaxis (STD-IP) (0.1 mg/kg/day, 3 days). METHODS: In this retrospective study, the primary outcome was perinatal brain injury (neuro-imaging evidence of intraventricular hemorrhage or periventricular leukomalacia) or death before discharge. A non-inferior efficacy of an SGL-IP regimen compared with a STD-IP regimen was determined by calculating the adjusted difference in the risk of the primary outcome using a multivariable logistic regression model. A 10-percentage point non-inferiority margin was favored. RESULTS: Prevalence rates of primary outcome were 41.7% in the SGL-IP group (n = 403) and 42.5% in the STD-IP group (n = 509) (adjusted risk difference: -1.2, 95% CI: -7.6 to +5.2, p = 0.71). CONCLUSION: Use of a single prophylactic indomethacin dose was as effective as a standard regimen in preventing perinatal brain injury.

A Rare Co-occurrence of Intestinal Malrotation and Hirschsprung's Disease in a Neonate with 13q21.31q33.1 Interstitial Deletion Including the EDNRB Gene.

We report a rare co-occurrence of intestinal malrotation and Hirschsprung's disease (HSCR) in a male neonate with a large 38.8 Mb interstitial deletion of chromosome 13 extending from q21.31 to q33.1 including the EDNRB gene, who presented with craniofacial dysmorphic features and central nervous system malformations. The loss of EDNRB gene in addition to bilateral hearing loss and HSCR suggested an additional diagnosis of Waardenburg-Shah's syndrome. This case highlights the fact that prior knowledge of this rare association in infants with 13q deletion syndrome would enable early diagnosis and prompt interventions to prevent gastrointestinal complications.

Unilateral Open-lip Schizencephaly with Tonsillar Herniation in a Preterm Infant.

Schizencephaly is a rare type of neuronal migration disorder characterized by the presence of a cerebral hemispheric cleft that extends from lateral ventricles to the cortical surface of the brain. We report a rare case of prenatally diagnosed unilateral schizencephaly in a late preterm infant who manifested with rapidly progressive hydrocephalus with massive enlargement of posterior cerebrospinal fluid spaces with tonsillar herniation that was successfully treated with placement of a ventriculoperitoneal shunt.