Prediction of short- and long-term outcomes using pre-operative ventricular size in infants with post-hemorrhagic ventricular dilation.

PURPOSE: Post-hemorrhagic ventricular dilation (PHVD) leads to developmental delays in premature infants, yet the optimal timing of neurosurgical interventions is unknown. Neuroimaging modalities have emerged to delineate injury and follow the progression of PHVD. Fronto-temporal horn ratio (FTHR) is used as a marker of ventricular dilation and can be a standardized tool to direct the timing of neurosurgical intervention. Our study determined a pre-operative FTHR measurement threshold to predict short- and long-term outcomes. METHODS: This is a retrospective cohort study of premature infants with severe intraventricular hemorrhage (IVH) who developed PHVD requiring neurosurgical intervention and were treated in a level IV NICU between 2012 and 2019. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were performed to evaluate the accuracy of pre-operative FTHR for predicting developmental delay. In-hospital outcomes and developmental assessments were analyzed. RESULTS: We reviewed 121 charts of infants with IVH and identified 43 infants with PHVD who required neurosurgical intervention. We found FTHR measurements were an excellent predictor of cognitive and motor delay with an AUC of 0.89 and 0.88, respectively. An average pre-operative FTHR of ≥ 0.67 was also associated with worse lung and feeding outcomes. There was excellent inter-observer reliability of individual components of FTHR measurements. CONCLUSIONS: Early intervention for PHVD is ideal but not always practical. Identification of ventricular size thresholds associated with better outcomes is needed to direct timing of neurosurgical intervention.

Evaluation and Immunogenicity of Combined Liposome-Based Vaccine Candidates against Hepatitis E and B Viruses in Rhesus Monkeys.

The administration of vaccines using a combination approach ensures better coverage and reduces the number of injections and cost. The present study assessed liposome-complexed DNA-corresponding proteins of hepatitis E and B viruses (HEV and HBV) as combined vaccine candidates in rhesus monkeys. The HEV and HBV components consisted of 450 bps, neutralizing the epitope/s (NE) region, and 685 bps small (S) envelope gene-corresponding proteins, respectively. Three groups (n = 2 monkeys/group) were intramuscularly immunized with a total of three doses of NE Protein (Lipo-NE-P), NE DNA + Protein (Lipo-NE-DP), and each of NE and S DNA + Protein (Lipo-NES-DP), respectively, given one month apart. All immunized monkeys were challenged with 10,000 fifty percent monkey infectious dose of homologous HEV strain. Post-immunization anti-HEV antibody levels in monkeys were 59.4 and 148.4 IU/mL (Lipo-NE-P), 177.0 and 240.8 IU/mL (Lipo-NE-DP), and 240.7 and 164.9 IU/mL (Lipo-NES-DP). Anti-HBV antibody levels in Lipo-NES-DP immunized monkeys were 58,786 and 6213 mIU/mL. None of the challenged monkeys showed viremia and elevation in serum alanine amino transferase levels. Monkeys immunized with Lipo-NE-DP and Lipo-NES-DP exhibited a sterilizing immunity, indicating complete protection, whereas monkeys immunized with Lipo-NE-P showed limited viral replication. In conclusion, the liposome-complexed DNA-corresponding proteins of HEV and HBV induced protective humoral immune responses to both components in monkeys and are worth exploring further.

Application of a truncated ORF2 protein-based ELISA for diagnosis of hepatitis E in an endemic area.

Enterically transmitted waterborne hepatitis E (HE) caused due to hepatitis E virus (HEV) prevails as a significant public health problem endemic to India. Due to short-term viremia/fecal excretion and poor in vitro transmissibility of HEV, HE diagnosis depends on detection of specific IgM antibodies in serum. Present study evaluated performances of two in-house and six commercial IgM detection enzyme-linked immunosorbent assays (ELISAs) using sera collected from volunteers/acute hepatitis patients (n = 716). The in-house ELISAs were based on complete and truncated open reading frame 2 (ORF2) proteins containing neutralizing epitope/s region of genotype 1 HEV (ORF2p, 1-660 amino acid (a.a.) and T1NEp, 458-607 a.a., respectively). The commercial ELISAs included Wantai (China), MP Diagnostics (MPD) (Singapore), DIA.PRO Diagnostics (Italy), MBS (Italy), abia (Germany), and ImmunoVision (USA). T1NE ELISA showed 97.0% positive percent agreement (PPA), 99.4% negative percent agreement (NPA), and 98.6% concordance (κ = 0.97, P = 0.0000) with ORF2 ELISA. ORF2, T1NE, Wantai, and MPD ELISAs agreed on results for 88% of sera tested. Two percent sera showed reactivity in each combination of three and two of aforementioned four ELISAs. Remaining 8% sera were single ELISA reactive. PPA and NPA value ranges were 76.3-99.0% and 84.8-99.5%, respectively. Pairwise concordances between all the eight ELISAs ranged from 88.0 to 100% (κ: 0.74-1.00). Both the in-house ELISAs agreed better with Wantai over MPD ELISA. In conclusion, both ORF2 and T1NE ELISAs were equally efficient in diagnosing HEV infections. T1NEp proved to be an excellent tool in HE sero-diagnosis and is worth exploring in development of simple rapid tests. KEY POINTS: • In-house ELISA based on bacterially expressed neutralizing epitope/s region protein • In-house ELISA based on complete ORF2 protein expressed in insect cells • Comparison of two in-house and six commercial anti-HEV IgM antibody detection ELISAs.

Task-based and Resting State Functional MRI in Children.

Functional MR imaging (MRI) is a valuable tool for presurgical planning and is well established in adult patients. The use of task-based fMRI is increasing in pediatric populations because it provides similar benefits for pre-surgical planning in children. This article reviews special adaptations that are required for successful applications of task-based fMRI in children, especially in the motor and language systems. The more recently introduced method of resting state fMRI is reviewed and its relative advantages and disadvantages discussed. Common pitfalls and other systems and networks that may be of interest in special circumstances also are reviewed.

Predictive Efficacy of Pediatric Logistic Organ Dysfunction-2 Score in Pediatric Intensive Care Unit of Rural Hospital.

AIMS AND OBJECTIVES: Utility of pediatric logistic organ dysfunction-2 (PELOD-2) score on day 1 within 1 hour of admission in predicting mortality in children admitted in pediatric intensive care unit (PICU). BACKGROUND: Various scoring systems aid to evaluate the patient's mortality risk in the intensive care unit (ICU) by assigning a score and predicting the outcome. Critically ill children are characterized by large variations in the normal body homeostasis. These variations can be estimated by the change of the physiological variables from the normal range. Various scores are constructed from deviations of these changed variables. One such score, the PELOD-2 score, is used to predict mortality of patients admitted in PICU. MATERIALS AND METHODS: This study was carried out at a tertiary care center in central India to study the utility of PELOD-2 score within 1 hour of admission to predict mortality in patients admitted in PICU. RESULTS: Total 129 patients were included in this study with mean age of 67 months. The system with highest admission was central nervous system with 42 children and 16.6% mortality, whereas those 7 patients with hematological system involvement had highest mortality of 28.5%. The mortality rate was 15.55%. In our study for PELOD-2 within 24 hours of admission, the area under receiver operating curve was 0.87 and the Hosmer-Lemeshow test was p = 0.42. CONCLUSION: Pediatric logistic organ dysfunction-2 score in our study had significant association with mortality along with the Hosmer-Lemeshow goodness-of-fit test showing a good prediction of mortality. HOW TO CITE THIS ARTICLE: Deshmukh T, Varma A, Damke S, Meshram R. Predictive Efficacy of Pediatric Logistic Organ Dysfunction-2 Score in Pediatric Intensive Care Unit of Rural Hospital. Indian J Crit Care Med 2020;24(8):701-704.

ACR Appropriateness Criteria® Cerebrovascular Disease.

Diseases of the cerebral vasculature represent a heterogeneous group of ischemic and hemorrhagic etiologies, which often manifest clinically as an acute neurologic deficit also known as stroke or less commonly with symptoms such as headache or seizures. Stroke is the fourth leading cause of death and is a leading cause of serious long-term disability in the United States. Eighty-seven percent of strokes are ischemic, 10% are due to intracerebral hemorrhage, and 3% are secondary to subarachnoid hemorrhage. The past two decades have seen significant developments in the screening, diagnosis, and treatment of ischemic and hemorrhagic causes of stroke with advancements in CT and MRI technology and novel treatment devices and techniques. Multiple different imaging modalities can be used in the evaluation of cerebrovascular disease. The different imaging modalities all have their own niches and their own advantages and disadvantages in the evaluation of cerebrovascular disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Imaging of Acute Pelvic Pain in Girls: Ovarian Torsion and Beyond☆.

Identifying the etiology of acute pelvic pain in girls is often clinically challenging. Particularly in young girls, it is often difficult to determine if acute pelvic symptoms are originating from a gynecologic source or from a genitourinary or gastrointestinal etiology based on the child's clinical examination alone. Therefore, imaging plays a key role in establishing a diagnosis and in directing medical and surgical treatment. Pediatric gynecologic conditions, which can present acutely with pain or mass or both include ovarian torsion, hematometrocolpos, pelvic inflammatory disease, inguinal hernias containing an ovary or the uterus or both, adnexal cysts, pregnancy, vaginal foreign bodies, and ovarian vein thrombosis. Sources of pelvic pain in girls from nongynecologic etiologies include appendicitis, distal ureterolithiasis, and Crohn's disease. Owing to the lack of ionizing radiation, widespread availability, and lack of need for sedation, gray scale, with color Doppler ultrasound examination is often the initial imaging obtained when there is suspicion of gynecologic pathology. Radiographs of the abdomen and pelvis are commonly used in the acute setting, when there is concern for a bowel obstruction or free intraperitoneal air. Cross-sectional imaging with computed tomography or magnetic resonance imaging is used, when the diagnosis remains unknown and to clarify findings found on ultrasound and radiographs. Correctly identifying and diagnosing the causes of acute pelvic pain in girls is crucial for the care of these patients. Here, we review the spectrum of causes of acute pelvic pain in female infants to teens with emphasis on imaging approach and age-related characteristics.

ACR Appropriateness Criteria Low Back Pain.

Most patients presenting with uncomplicated acute low back pain (LBP) and/or radiculopathy do not require imaging. Imaging is considered in those patients who have had up to 6 weeks of medical management and physical therapy that resulted in little or no improvement in their back pain. It is also considered for those patients presenting with red flags raising suspicion for serious underlying conditions, such as cauda equina syndrome, malignancy, fracture, and infection. Many imaging modalities are available to clinicians and radiologists for evaluating LBP. Application of these modalities depends largely on the working diagnosis, the urgency of the clinical problem, and comorbidities of the patient. When there is concern for fracture of the lumbar spine, multidetector CT is recommended. Those deemed to be interventional candidates, with LBP lasting for > 6 weeks having completed conservative management with persistent radiculopathic symptoms, may seek MRI. Patients with severe or progressive neurologic deficit on presentation and red flags should be evaluated with MRI. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (the RAND/UCLA Appropriateness Method and the Grading of Recommendations Assessment, Development, and Evaluation) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria Dementia and Movement Disorders.

Neurodegenerative disease, including dementia, extrapyramidal degeneration, and motor system degeneration, is a growing public health concern and is quickly becoming one of the top health care priorities of developed nations. The primary function of anatomic neuroimaging studies in evaluating patients with dementia or movement disorders is to rule out structural causes that may be reversible. Lack of sensitivity and specificity of many neuroimaging techniques applied to a variety of neurodegenerative disorders has limited the role of neuroimaging in differentiating types of neurodegenerative disorders encountered in everyday practice. Nevertheless, neuroimaging is a valuable research tool and has provided insight into the structure and function of the brain in patients with neurodegenerative disorders. Advanced imaging techniques, such as functional neuroimaging with MRI and MR spectroscopy, hold exciting investigative potential for better understanding of neurodegenerative disorders, but they are not considered routine clinical practice at this time. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Serum immunoglobulin G subclass responses in different phases of hepatitis E virus infection.

To investigate the specific immunoglobulin (Ig) G subclass responses in patients with hepatitis E virus (HEV) infection, an open reading frame 2 (ORF2) protein based enzyme-linked immunosorbant assay was used to measure antibody levels in sera obtained at different phases of infection. Sera were collected at 2-31 days and at 6 months after the onset of symptoms corresponding to the acute (n = 48, 100% IgM-positive) and convalescent (n = 17/48, 53% IgM-positive) phases of infection, respectively. IgM-negative sera from 61 individuals infected at least ≥6 months ago (prior exposure) were also tested. IgG1, IgG2, IgG3, and IgG4 antibodies were detected in 100%, 6%, 56%, and 4% of acute phase sera, respectively, and in 100%, 0%, 0%, and 65% of convalescent phase sera, respectively. IgG1 antibody levels were significantly higher than those of the other detectable subclasses of IgG in the acute and convalescent sera (P < 0.05). The IgG3 antibodies in six acute phase patients were replaced by IgG4 antibodies in the convalescent phase of infection. Patients with prior exposure to HEV had low total IgG antibody titers and decreased IgG1 seropositivity compared with those in the acute and convalescent phases. IgG1 was the only major subclass of antibody to be detected in all the three phases of infection. Other than IgG1 antibodies, the subclass antibody response was restricted to IgG3 and IgG4 antibodies in the acute and convalescent phases of infection, respectively.

Challenge studies in Rhesus monkeys immunized with candidate hepatitis E vaccines: DNA, DNA-prime-protein-boost and DNA-protein encapsulated in liposomes.

Complete ORF2 gene (1983bp) of hepatitis E virus (HEV) and the 450bp region within ORF2 containing neutralizing epitope (NE) cloned in pVAX1 and corresponding proteins expressed in baculovirus and prokaryotic systems respectively were evaluated as vaccine candidates. Two doses of liposome encapsulated DNA plus corresponding protein with both ORF2 and NE regions (Lipo-ORF2-DP and Lipo-NE-DP) showed 100% seroconversion and comparable anti-HEV titres in Swiss albino mice. These vaccine candidates were further evaluated as DNA, DNA-prime-protein-boost (DPPB) and liposome formulations in Rhesus monkeys. Monkeys receiving ORF2/NE DNA seroconverted after fourth dose while those immunized employing ORF2-DPPB format seroconverted at 7 weeks post third dose. In view of the delayed weak antibody response, these monkeys were not challenged. Though Lipo-ORF2-DP was immunogenic, 2 of the 4 monkeys developed HEV infection following homologous virus challenge of 100 Monkey Infectious Dose(50). Both monkeys immunized with Lipo-NE-DP and 1 of the 2 monkeys immunized with NE-DPPB showed complete protection, the second monkey being protected from hepatitis with limited viral replication. Irrespective of the type of immunogen, all challenged monkeys were protected from hepatitis. The results document Lipo-NE-DP to be a promising vaccine candidate needing further evaluation.

MRI features of tuberculosis of the knee.

OBJECTIVE: The objective of this study was to describe the magnetic resonance imaging (MRI) features of tuberculosis (TB) of the knee joint. MATERIALS AND METHODS: The MRI features in 15 patients with TB of the knee, as confirmed by histology of the biopsied joint synovium, were reviewed retrospectively. The images were assessed for intra-articular and peri-articular abnormalities. RESULTS: All patients had florid synovial proliferation. The proliferating synovium showed intermediate to low T2 signal intensity. In the patients who were administered intravenous contrast, the hypertrophic synovium was intensely enhancing. Marrow edema (n = 9), osteomyelitis (n = 4), cortical erosions (n = 5), myositis (n = 6), cellulitis (n = 2), abscesses (n = 3), and skin ulceration/sinus formation (n = 2) were seen in the adjacent bone and soft tissue. CONCLUSION: Synovial proliferation associated with tuberculous arthritis is typically hypointense on T2-weighted images. This appearance, in conjunction with other peri-articular MRI features described, can help in distinguishing TB arthritis from other proliferating synovial arthropathies.

Immunogenicity of candidate hepatitis E virus DNA vaccine expressing complete and truncated ORF2 in mice.

Hepatitis E virus (HEV) is a major cause of enterically transmitted acute hepatitis of adults in developing nations. Our present studies show that, the complete ORF2 gene (1-660 amino acids, a.a.) coding for capsid protein of HEV as candidate DNA vaccine induced significant specific humoral and cellular immune responses in mice. Gene gun based DNA administration led to higher seroconversion rates and HEV-specific antibody titers as against needle-injection method. The region (458-607a.a.) within ORF2 protein is reported to harbour the predominant neutralization epitope/s (NE) of HEV. The NE DNA also induced HEV-specific immune responses in mice. NE-based DNA-prime-protein boost approach was observed to be superior to NE DNA based approach. Co-administration of plasmid expressing mouse granulocyte macrophage colony stimulating factor (GM-CSF) induced immune response at similar level as that with ORF2/NE plasmid alone. IgG1 was the predominant isotype irrespective of the approach used. HEV-specific antibodies in seroconverted mice sera could bind/neutralize HEV in an in vitro ELISA-based assay. In conclusion, efficacy of ORF2 and NE based DNA/DNA-prime-protein-boost approaches are worth exploring in monkey model.

Complete large bowel duplication with paraduodenal cyst: prenatal sonographic features.

OBJECTIVES: To illustrate diagnostic dilemmas while considering a diagnosis of complete large bowel duplication and duodenal duplication cysts. METHODS: A case of large bowel dilatation with a peripancreatic cyst was identified sonographically in a 27-year-old gravida 3 at 35 weeks of gestation, suffering from gestational diabetes and pregnancy-induced hypertension. RESULTS: On the basis of sonographic findings of dilated, hyperperistaltic large bowel loops, and a large cyst with echo-free contents near the pancreas, a diagnosis of large bowel obstruction with a paraduodenal cyst was considered. The findings were confirmed after postnatal ultrasonography. At the time of surgery, it proved to be a completely duplicated large bowel with a paraduodenal cyst. CONCLUSION: Prenatal findings of a hugely dilated, hyperperistaltic large bowel should lead one to suspect/consider large bowel duplication. Associated cysts are likely to be bowel duplication cysts. Timely intervention can thus obviate potentially serious complications.