Pneumococci isolated from children in community-based practice differ from isolates identified by population and laboratory-based invasive disease surveillance.

BACKGROUND: Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs). METHODS: During 2011-2019, among children aged 6-36 months, pneumococcal serotype distribution and antibiotic non-susceptibility of nasopharyngeal and middle ear fluid (MEF) isolates collected at onset of acute otitis media (AOM) in Rochester, New York were compared with IPD isolates from Active Bacterial Core surveillance (ABCs) across 10 U.S. sites. RESULTS: From Rochester, 400 (nasopharyngeal) and 156 (MEF) pneumococcal isolates were collected from 259 children. From ABCs, 907 sterile-site isolates were collected from 896 children. Non-PCV serotypes 35B and 21 were more frequent among the Rochester AOM cases, while serotypes 3, 19A, 22F, 33F, 10A, and 12F contained in PCVs were more frequent among ABCs IPD cases. The proportion of antibiotic non-susceptible pneumococcal isolates was generally more common among IPD cases. In 2015-2019, serotype 35B emerged as the most common serotype associated with multiclass antibiotic non-susceptibility for both the Rochester AOM and ABCs IPD cases. CONCLUSIONS: Pneumococcal isolates from children in Rochester with AOM differ in serotype distribution and antibiotic susceptibility compared to IPD cases identified through U.S. surveillance. Non-PCV serotype 35B emerged as a common cause of AOM and IPD.

Expression conditions and characterization of a novelly constructed lipoprotein intended as a vaccine to prevent human Haemophilus influenzae infections.

Bacterial lipoproteins are structurally divided into two groups, based on their lipid moieties: diacylated (present in Gram-positive bacteria) and triacylated (present in some Gram-positive and most Gram-negative bacteria). Diacylated and triacylated lipid moieties differ by a single amide-linked fatty acid chain. Lipoproteins induce host innate immune responses by the mammalian Toll-like receptor 2 (TLR2). In this study, we added a lipid moiety to recombinant OMP26, a native nonlipidated (NL) membrane protein of Haemophilus influenzae, and characterized it extensively under different expression conditions using flow cytometry, LC/MS, and MALDI-TOF. We also investigated the ability of NL and lipidated (L) OMP26 to induce in vitro stimulation of HEK Blue-hTLR2-TR1 and hTLR-TLR6 cells. Our L-OMP26 was predominantly expressed in diacylated form, so we employed an additional gene copy of apolipoprotein N-acetyltransferase enzyme (Lnt)-rich Escherichia coli strain that further acylates the diacyl lipoproteins to enhance the production of triacylated L-OMP26. The diacyl and triacyl versions of L-OMP26, intended as a vaccine for use in humans, were characterized and evaluated as protein vaccine components in a mouse model. We found that the diacyl and triacyl L-OMP26 protein formulations differed markedly in their immune-stimulatory activity, with diacylated L-OMP26 stimulating higher adaptive immune responses compared with triacylated L-OMP26 and both stimulating higher adaptive immune response compared to NL-OMP26. We also constructed and characterized an L-OMP26φNL-P6 fusion protein, where NL-P6 protein (a commonly studied H. influenzae vaccine candidate) was recombinantly fused to L-OMP26. We observed a similar pattern of lipidation (predominantly diacylated) in the L-OMP26φNL-P6 fusion protein.

Impact of pancreas transplantation alone on kidney function: A multicenter clinical cohort study.

Pancreas transplantation alone (PTA) is a ß cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m2 , and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10-year eGFR (mL/min/1.73 m2 ) were 76.3 (58.1-100.8) and 51.3 (35.3-65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post-transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post-PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death-censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.

Evaluation of fetal kidney length as a marker for fetal biometry.

BACKGROUND: The precise determination of gestational age is essential for effectively managing and prognosis of all pregnancies. Through careful biometry, timely interventions can be implemented, leading to positive outcomes for both the mother and fetus. In routine fetal biometry, parameters such as biparietal diameter (BPD), femur length (FL), head circumference (HC), and abdominal circumference (AC) have been traditionally used. This study aims to evaluate the usefulness of fetal kidney length (FKL) as a marker for fetal biometry. METHODOLOGY: This prospective, observational, and cross-sectional study was conducted in the Radiodiagnosis and Obstetrics and Gynaecology departments, including a diverse group of pregnant women from various socio-economic backgrounds, with adherence to ethical standards. Women with singleton pregnancies between 22 and 40 weeks of gestation who met the inclusion and exclusion criteria were examined through ultrasound. The data collected were subsequently analyzed. RESULT: In the current study, 280 participants with an average age of 26.71 ± 3.6 years were included. The agreement between the mean fetal kidney length and standard biometry parameters was almost perfect, with a strength of agreement exceeding 0.99. A strong and statistically significant positive correlation existed between fetal kidney length and the estimated gestational period calculated using DLMP/standard biometric measurements. CONCLUSION: Fetal kidney length is a reliable indicator of gestational age and can supplement standard biometric measurements to provide a more precise estimation of gestational age, especially in the later stages when obtaining such standard measurements may be challenging.

Insight into the Burden of Antimicrobial Resistance among Bacterial Pathogens Isolated from Patients Admitted in ICUs of a Tertiary Care Hospital in India.

Intensive care unit (ICU) patients are prone to develop infections by hospital prevalent organisms. The aim of the study was to determine the bacteriological profiles and their drug resistance pattern among different infections in ICU patients of a tertiary care hospital. The record-based retrospective data of culture reports of the patients admitted to all the ICUs of a tertiary care hospital during the period from January 2020 to May 2022 were analyzed. A total of 3,056 samples were obtained from 2308 patients. The infection rate among ICU patients was found to be 53.40%. Isolates belonged equally to males (50.86%) and females (49.14%). The most common culture-positive clinical specimen received was blood (39.08%) followed by respiratory samples (29.45%). Acinetobacter sp. (33.02%) was the most common organism isolated from various clinical specimens, followed by Klebsiella pneumoniae (20.89%), and Escherichia coli (13.8%). More than 80% of Acinetobacter species were found to be resistant to third-generation cephalosporins, aminoglycosides, and carbapenems, whereas minocycline (56.31% S) and colistin (100% S) were the most effective drugs. Klebsiella sp. was found to be more resistant than E.coli, and the least resistance was observed to be tetracycline (43.97%) and doxycycline (55.84%). Among Staphylococcus aureus, 82.78% of strains were methicillin-resistant (MRSA). Vancomycin-resistant Enterococci (VRE) sp. accounted for 16.67% of the isolates. Evidence-based knowledge regarding the local bacterial organisms and their antimicrobial resistance pattern is pivotal in deciding empirical drug therapy, ultimately leading to the management of antimicrobial resistance (AMR).

Variability of Vaccine Responsiveness in Young Children.

BACKGROUND: Variability in vaccine responsiveness among young children is poorly understood. METHODS: Nasopharyngeal secretions were collected in the first weeks of life for measurement of cytokines/chemokines seeking a biomarker, and blood samples collected at age one year to identify vaccine responsiveness status, defined as low vaccine responder (LVR), normal (NVR) and high (HVR), to test for vaccine antigen-induced immune memory, and for antigen presenting cell (APC) function. RESULTS: Significantly lower specific cytokine/chemokine levels as biosignatures, measurable in nasopharyngeal secretions at infant age 1-3 weeks old, predicted LVR status compared to NVR and HVR children. Antibiotic exposures were correlated with increased occurrence of LVR. At age 1 year old, LVRs had fewer CD4+ T-helper-1 and T-helper-2 memory cells responsive to specific vaccine antigens. APC responses observed among LVRs, both at rest and in response to TLR7/8 stimulation by R848 were suboptimal, suggesting that altered innate immunity may contribute to immune deficiency in LVRs. CONCLUSION: Cytokine biosignatures in the first weeks of life may predict vaccine responsiveness in children during the first year of life. Antibiotic exposure associates with LVR in children. CD4+ T-cell memory induction and APC deficiencies occur in LVR children.

Vaccine target and carrier molecule nontypeable Haemophilus influenzae protein D dimerizes like the close Escherichia coli GlpQ homolog but unlike other known homolog dimers.

We have determined the 1.8 Å X-ray crystal structure of nonlipidated (i.e., N-terminally truncated) nontypeable Haemophilus influenzae (NTHi; H. influenzae) protein D. Protein D exists on outer membranes of H. influenzae strains and acts as a virulence factor that helps invade human cells. Protein D is a proven successful antigen in animal models to treat obstructive pulmonary disease (COPD) and otitis media (OM), and when conjugated to polysaccharides also has been used as a carrier molecule for human vaccines, for example in GlaxoSmithKline Synflorix™. NTHi protein D shares high sequence and structural identify to the Escherichia coli (E. coli) glpQ gene product (GlpQ). E. coli GlpQ is a glycerophosphodiester phosphodiesterase (GDPD) with a known dimeric structure in the Protein Structural Database, albeit without an associated publication. We show here that both structures exhibit similar homodimer organization despite slightly different crystal lattices. Additionally, we have observed both the presence of weak dimerization and the lack of dimerization in solution during size exclusion chromatography (SEC) experiments yet have distinctly observed dimerization in native mass spectrometry analyses. Comparison of NTHi protein D and E. coli GlpQ with other homologous homodimers and monomers shows that the E. coli and NTHi homodimer interfaces are distinct. Despite this distinction, NTHi protein D and E. coli GlpQ possess a triose-phosphate isomerase (TIM) barrel domain seen in many of the other homologs. The active site of NTHi protein D is located near the center of this TIM barrel. A putative glycerol moiety was modeled in two different conformations (occupancies) in the active site of our NTHi protein D structure and we compared this to ligands modeled in homologous structures. Our structural analysis should aid in future efforts to determine structures of protein D bound to substrates, analog intermediates, and products, to fully appreciate this reaction scheme and aiding in future inhibitor design.

Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018-February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34), and median birth weight was 1270 gr (interquartile range [IQR]: 990-1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.

Our study describes neonates from low- and middle-income countries with neonatal invasive candidiasis (NIC). Most of them were outside the groups considered at high risk for NIC described in high-income countries. Candida spp. epidemiology was also different. The mortality was high (22%). Further research in these settings is required.

Does ensuring optimum vitamin D levels result in early resolution of neurocysticercosis?

BACKGROUND: Neurocysticercosis is a leading cause of acquired epilepsy. Calcified granulomas are known to cause seizure recurrence. Researchers have reported that vitamin D deficiency is associated with brain calcification and reduction in calcification occurs with vitamin D receptor agonist calcitriol through upregulation of SLC20A2. Based on these observations, a hypothesis was proposed that the occurrence of calcification could be reduced by optimizing vitamin D levels, resulting in early resolution of neurocysticercosis. METHODOLOGY: A case-control (retrospective and prospective) study on 60 children with solitary intraparenchymal neurocysticercosis, 20 new cases prior to starting cysticidal therapy and other 40 resolved cases was carried out. Among new cases, children deficient in vitamin D were given megadose of vitamin D and vitamin D levels were rechecked after 30 days. Children having normal vitamin D were taken as cases and the deficient ones were taken as controls. Standard treatment for neurocysticercosis was given. Three monthly MRI scans were done. Outcome was evaluated as resolution/persistence of neurocysticercosis at 3, 6, 9 and 12 months. STATISTICS AND RESULTS: Pearson chi square/Fisher's exact test was used along with Kaplan Meier and log rank test. Of 60 patients, at 6 months 3 cases and 4 controls (p value 0.43), at 9 months 2 cases and 6 controls (p value 0.037) and at 12 months 3 cases and 6 controls (p value 0.029) had complete resolution of NCC. CONCLUSION: The results do not show that adequate vitamin D levels result in early resolution of neurocysticercosis.

Comparison of "ligamentization" process between preserved insertion hamstring tendon autograft and bone-patellar tendon-bone autograft.

BACKGROUND: Ligamentization is a complex process and effect of preservation of hamstring tendon graft insertion on this process is not well studied. Present study was conducted to analyze and compare the ligamentization of semitendinosus gracilis graft with preserved tibial insertion (STGPI) and bone-patellar tendon-bone (BPTB) autografts. METHODS: A total of 50 sportspeople who underwent ACL reconstruction using either BPTB (group A; n = 25) or STGPI (group B; n = 25) autografts were included in the study. Contrast enhanced MRI was done at 8 months and 14 months post-ACL reconstruction to evaluate the ligamentization using Signal noise quotient (SNQ), graft intensity and enhancement index. Clinical outcomes (Lysholm score) and knee laxity were also assessed at 8 months and 14 months. RESULTS: 18/23 (78%) patients in group A and 14/23 (61%) patients in group B had hyperintense graft signal at 8 months (n.s.) and at 14 months, 1/23 patients in group A and none of the patients in group B had hyperintense graft. SNQ at 8 months was 3.6 ± 2 and 3.7 ± 2 in group A and B respectively (n.s.) and at 14 months, SNQ was 2.5 ± 1.5 in group A and 2.4 ± 1.3 in group B (n.s.). Enhancement index at 8 months was 1.5 ± 0.3 and 1.2 ± 0.3 in group A and B respectively (p = 0.0001). Enhancement index at 14 months was 1.21 ± 0.2 in group A and 1.07 ± 0.2 in group B (p = 0.003). Functional outcomes and knee laxity were comparable in both the groups at 8 and 14 months (n.s.). CONCLUSION: Both the grafts i.e. BPTB and STGPI are similar in terms of rate and extent of ligamentization. Clinical outcomes and knee laxity are also comparable between two grafts.

Role of Magnetic Resonance Mammography in the Evaluation of Indeterminate Breast Lesions.

Background: Malignancy of the breast is one of the most common cancers among females worldwide. Magnetic resonance mammography (MRM) is a valuable complement to conventional methods for the early diagnosis of disease, thereby providing patients with a better prognosis. The number of unnecessary biopsies and repeated excisions in cases of indeterminate breast lesions detected on conventional imaging is high. Aims: The purpose of this study was to evaluate the role of MRM in the evaluation of indeterminate breast lesions [Breast Imaging Reporting and Data System (BIRADS) 3/4] found in conventional mammography and ultrasonography (USG), taking the histopathological examination (HPE) as the gold standard. Materials and methods: A total of 38 patients with conventional radiological imaging diagnosis of indeterminate breast lesions (BIRADS 3/4) were included in this study and evaluated using contrast-enhanced MRM according to the MR-BIRADS lexicon (5th edition). Morphological characteristics of lesions were evaluated to determine the probability of malignancy. Histopathology was kept as the gold standard for comparing all the statistical parameters. Results: There were a total of 40 lesions, 35 masses, and five nonmass enhancement (NME) available for evaluation out of the 38 patients. The sensitivity of margins to detect malignancy approached 100%; however, it had a slightly lower specificity of 66.67%. Magnetic resonance imaging (MRI) showed good diagnostic performance with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 85, 90, 89.47, 85.71, and 87.50%, respectively. Conclusion: The MRI has been shown to be useful as a problem-solving tool in breast cancer screening, clarifying indeterminate findings and avoiding unnecessary short follow-ups and percutaneous biopsies. How to cite this article: Mishra E, Kaur N, Kaur R, et al. Role of Magnetic Resonance Mammography in the Evaluation of Indeterminate Breast Lesions. J Assoc Physicians India 2023;71(11):76-84.

Lipidation of Haemophilus influenzae Antigens P6 and OMP26 Improves Immunogenicity and Protection against Nasopharyngeal Colonization and Ear Infection.

Nontypeable Haemophilus influenzae (NTHi) causes respiratory infections that lead to high morbidity and mortality worldwide, encouraging development of effective vaccines. To achieve a protective impact on nasopharyngeal (NP) colonization by NTHi, enhanced immunogenicity beyond that achievable with recombinant-protein antigens is likely to be necessary. Adding a lipid moiety to a recombinant protein would enhance immunogenicity through Toll-like receptor 2 signaling of antigen-presenting cells and Th17 cell response in the nasal-associated lymphoid tissue (NALT). We investigated effects of lipidation (L) of recombinant proteins P6 and OMP26 compared to nonlipidated (NL) P6 and OMP26 and as fusion constructs (L-OMP26ϕNL-P6 and L-P6ϕNL-OMP26) in a mouse model. After intraperitoneal or intranasal vaccination, antibody responses were compared and protection from NP colonization and middle ear infection were assessed. L-P6 and L-OMP26 induced approximately 10- to 100-fold-higher IgG antibody levels than NL-P6 and NL-OMP26. Fusion constructs significantly increased IgG antibody to both target proteins, even though only one of the proteins was lipidated. NP colonization and middle ear bullae NTHi density was 1 to 4 logs lower following vaccination with L-P6 and L-OMP26 than with NL-P6 and NL-OMP26. Fusion constructs also resulted in a 1- to 3-log-lower NTHi density following vaccination. NALT cells from mice vaccinated with lipidated protein constructs had higher levels of interleukin-17 (IL-17), IL-22, and CD4+ T-cell memory. Passive transfer of sera from L-OMP26ϕNL-P6-vaccinated mice to recipient infant mice reduced NP colonization and ear bulla NTHi density. We conclude that L-P6, L-OMP26, and fusion constructs generate enhanced antibody responses and protection from NP colonization and middle ear infection by NTHi in mice.

Dynamic changes in otopathogens colonizing the nasopharynx and causing acute otitis media in children after 13-valent (PCV13) pneumococcal conjugate vaccination during 2015-2019.

The otopathogens colonizing the nasopharynx (NP) and causing acute otitis media (AOM) have shown dynamic changes following introduction of pneumococcal conjugate vaccines. Five hundred eighty-nine children were prospectively enrolled, 2015-2019. Two thousand fifty-nine visits (1528 healthy, 393 AOM, and 138 AOM follow-up) were studied. Two thousand forty-two NP and 495 middle ear fluid (MEF) samples by tympanocentesis from 319 AOM cases were cultured for bacterial identification and antibiotic susceptibility. Streptococcus pneumoniae (Spn) isolates were serotyped by Quellung, and multi-locus sequence type (ST) determined by genomic analysis. Haemophilus influenzae (Hi) was the most common otopathogen cultured from MEF during AOM (34% in MEF) followed by Spn (24% in MEF), then Moraxella catarrhalis (Mcat) (15% in MEF). NP isolates during healthy visit were Mcat (39%), Spn (32%), Hi (12%). 48.6% of Hi isolates from MEF were beta-lactamase-producing. Spn non-susceptibility to penicillin and other antibiotics was high. The most common Spn serotypes associated with AOM (and colonizing the NP during healthy visits) were 35B, 23B, and 15B/C. ST558 and ST199 were the most common sequence types. During 2015-2019, Hi was the most common otopathogen cultured from MEF during AOM among young children. Pneumococcal AOM was most commonly caused by non-PCV13 serotypes of Spn, predominantly 35B, 23B, and 15B/C. Resistance to common antibiotics among Spn strains showed an increasing trend.

Is there fungal infestation in paediatric chronic otitis media - Mucosal disease?

OBJECTIVES: To determine the prevalence of fungal infestation in paediatric chronic otitis media (COM)-mucosal disease and to study the various factors that might influence the said infestation. METHODS: A cross-sectional study was done on the cited subject in a sample size of 66 paediatric patients [Age group: 1-18 years] suffering from active COM-mucosal disease. In all we had 75 ears from which swab samples were taken as some patients had bilateral disease. Clinical record was documented in each case. Three sample swabs were analysed for aerobic, anaerobic and fungal infection respectively from the discharging ear. Fungal infection was diagnosed by culture. The data was tabulated and statistically analysed for any correlation of fungal infestation with age, sex, background, duration of COM, previous antibiotic/steroid usage and intractable otorrhoea. RESULTS: We recorded a prevalence of 32% for fungal colonization of COM-mucosal disease in paediatric population i.e., 24 out of 75 ears. There was no association observed between fungal infestation and specific paediatric age group, sex, background or duration of the disease. However, a distinct statistical correlation was present between fungal infestation and previous antibiotic/steroid usage and intractable otorrhoea. CONCLUSION: Findings of this study lead us to conclude that all cases of paediatric COM-mucosal disease should be analysed for fungal colonization, especially those with intractable otorrhoea and there should be judicious use of antibiotics and steroid ear drops in COM-mucosal disease.

Evaluation of double lung point sign as a marker for transient tachypnoea of the newborn in preterm.

Purpose: The study was conducted to diagnose transient tachypnoea of the newborn (TTN) in the early stage using ultrasonography and to estimate the sensitivity and specificity of double lung point (DLP) sign in diagnosing TTN. Material and methods: The study population included premature neonates with respiratory distress, admitted in the neonatal intensive care unit from December 2017 to June 2019, who fulfilled the inclusion criteria. A total of 100 patients were included in the study, and they underwent lung ultrasonography within 6 hours of birth. Inclusion criteria were as follows: preterm babies born < 37 weeks of gestation presenting with respiratory distress within 6 hours, clinically diagnosed with TTN and other causes like respiratory distress syndrome and pneumonia. Term neonates and neonates with congenital malformations and trauma were excluded from the study. Preterms with respiratory distress were enrolled in the study. Based on the clinical findings and laboratory investigations, clinical diagnosis was made by the paediatrician. After obtaining informed consent, ultrasonography of bilateral chest was performed using a Philips HD7 XE and a Sonoscape S2 portable ultrasound machine with a linear transducer (6-12 MHz) within 6 hours of birth. Results: The mean gestational age was 33.0 ± 1.9 weeks. Double lung point sign was present in 55 preterm neonates in our study. It was most common in bilateral posterior lung fields. The sensitivity and specificity of DLP in diagnosing TTN was 85% and 100%, respectively. Conclusions: It was found in our study that double lung point sign is the primary ultrasonographic characteristic of TTN, and ultrasonography can almost accurately diagnose TTN in early stages.

Hirayama disease: neutral and flexion magnetic resonance imaging and utility of inter-segmental angle of flexion.

Purpose: Hirayama disease (HD) is a rare disease that was commonly mis-diagnosed in the past. The importance of neutral and flexion magnetic resonance imaging (MRI) in its accurate diagnosis has been emphasized along with utility of the inter-segmental angle of flexion. Aim of the study was to observe MRI findings of HD in neutral and flexion position and measure the inter-segmental angle of flexion. Material and methods: Cervical MR images of 17 patients of suspected HD were evaluated retrospectively for loss of attachment (LOA) of posterior dura, lower cervical cord atrophy, T2 hyperintensity, loss of cervical lordosis, enhancement of posterior epidural venous plexus, and inter-segmental angle of flexion on neutral and flexion MRIs. Results: Flexion MRI showed LOA of posterior dura (most commonly and maximum at C6 vertebral level) and intense enhancement in posterior epidural space in almost all patients. The mean inter-segmental angle of flexion at C5-C6 was 9.2°, and at C6-C7 it was 6°. Neutral MRI revealed LOA in 64.7%, lower cervical cord atrophy in all patients, T2 hyperintensity in the lower cervical cord in 35.2% of patients, and loss of cervical lordosis in 58.8% of patients. Conclusions: Flexion MRI is the gold standard for diagnosis of HD; however, certain imaging attributes, i.e. loss of attachment of posterior dura, asymmetrical lower cervical cord atrophy, T2 hyperintensity, and loss of cervical lordosis, can be seen on neutral MRI as well, which subsequently prompts the radiologist to include flexion MRI for confirmation. The inter-segmental angle of flexion is increased in patients with HD, which plays a role in planning timely surgical intervention.

Rising Pneumococcal Antibiotic Resistance in the Post-13-Valent Pneumococcal Conjugate Vaccine Era in Pediatric Isolates From a Primary Care Setting.

BACKGROUND: Antibiotic-resistant Streptococcus pneumoniae strains may cause infections that fail to respond to antimicrobial therapy. Results reported from hospitalized patients with invasive, bacteremic infections may not be the same as those observed in a primary care setting where young children receive care for noninvasive infections. Young children experience the highest burden of pneumococcal disease. The aim of this study was to determine the antibiotic susceptibility of S. pneumoniae strains isolated from children in a primary care setting in the post-13-valent pneumococcal conjugate vaccine (PCV13) era. METHODS: This was a prospective collection of 1201 isolates of S. pneumoniae from 2006 through 2016 in a primary care setting. Antibiotic susceptibility testing to 16 different antibiotics of 10 classes was performed. Participants were children aged 6-36 months. Nasopharyngeal swabs were obtained from patients during acute otitis media (AOM) visits and routine healthy visits. Middle ear fluid was obtained by tympanocentesis. RESULTS: After introduction of PCV13, antibiotic susceptibility of pneumococci, especially to penicillin, initially improved largely due to disappearance of serotype 19A, included in PCV13. However, beginning in 2013, antibiotic susceptibility among pneumococcal strains began decreasing due to new serotypes not included in PCV13. In addition to reduced susceptibility to penicillin, the most recent isolates show reduced susceptibility to third-generation cephalosporins, fluoroquinolones, and carbapenems, antibiotics commonly used to treat life-threatening, invasive pneumococcal diseases. CONCLUSIONS: In recent years, pneumococcal nasopharyngeal and AOM isolates from children exhibit reduced susceptibility to penicillin, third-generation cephalosporin, fluoroquinolone, and carbapenem antibiotics. The new strains have a different profile of resistance compared to the pre-PCV13 era.

Comparison of specific in-vitro virulence gene expression and innate host response in locally invasive vs colonizer strains of Streptococcus pneumoniae.

Among Rochester NY children, a dramatic increase in nasopharyngeal (NP) colonization by non-vaccine pneumococcal serotypes 35B and 15A occurred during years 2010-2015, after introduction of 13-valent pneumococcal conjugate vaccine (PCV13). In our population, serotype 35B strains colonized in the nasopharynx (NP) but infrequently caused acute otitis media (AOM) whereas serotype 15A strains displayed virulence, evidenced by causing AOM. To explain the virulence difference, virulence genes expression between 35B and 15A, as well as the host's immune response during asymptomatic colonization were analyzed. We investigated differences in regulation of 19 virulence genes for differences in virulence using RT-PCR in 20 35B and 14 15A strains and measured gene expression of 9 host innate cytokines in the NP to assess the mucosal inflammatory response during asymptomatic colonization. Comparing 35B versus 15A strains, genes for competence ComA and RrgC were upregulated; capsular (Cps2D) and virulence genes (PfbA, PcpA and PhtE) were downregulated among 35B strains. PavB, LytA, LytB, NanA, CiaR, PhtD, LuxS, PspA and pneumolysin (Ply) showed no difference. IL17 and IL23 gene expression were > tenfold higher during 35B compared to 15A strain asymptomatic colonization. Only IL23 showed significant difference. In the first 5 years after introduction of PCV13, serotype 35B strains emerged as asymptomatic colonizers and 15A strains emerged to cause AOM in young children. Various genes (PfbA, PcpA, Cps2D and PhtE) among tested in this analysis were downregulated in 35B whereas ComA and RrgC were significantly upregulated. For the host's cytokine response, IL23 proinflammatory response which is essential for the differentiation of Th17 lymphocytes in the NP of children with 35B strains was significantly higher than the response to 15A during asymptomatic colonization.

Male pseudohermaphrodite with persistent Mullerian duct: A radiologist's and patient's dilemma alike.

This case study highlights that how a disorder of sexual development when goes unnoticed at birth and unreported during childhood or adolescence can present with major problems and even complications in adulthood. Since our patient was young and in a childbearing age, he presented with bilateral undescended testes and orgasmic anejaculation when he first came to the hospital. Subsequently, having a normal 46XY karyotype but remnants of persistent Mullerian duct made him little confused about his identity. After giving him the confidence, that he was still a male and could lead the life he did previously, the explanation about future risk of malignancy in the intra-abdominal testes was another difficult task. Early detection and management of male pseudohermaphroditism with persistent Mullerian duct requires a co-ordinated approach of a team of endocrinologist, physician, surgeon and radiologist. Integrated imaging in the form of ultrasound, genitography and MRI is important in demonstrating the anatomy, classification, possible effects or congenital malformations in other organs, warning patients of any risk of neoplasia and guiding the clinician to plan other investigations, hormonal replacement or reconstruction surgery if required. Such a systemic approach that allays anxiety and gives psychological relief to the patient should be taken as it can deeply change the life of a person and their family.

The role of chemical shift magnetic resonance imaging in differentiating osteoporotic benign and malignant vertebral marrow lesions.

PURPOSE: To evaluate the usefulness of chemical shift imaging (CSI) in differentiating benign osteoporotic and malignant vertebral marrow lesions. MATERIAL AND METHODS: Patients undergoing spinal magnetic resonance imaging (MRI) for back pain, which showed altered marrow signal intensity on conventional MRI sequences, were included in the study. Patients with acute traumatic vertebral fractures, infective spondylodiscitis, paravertebral collections, etc. were excluded. The patients underwent CSI. In-phase and opposed-phase images were taken to calculate the signal intensity ratio (SIR) of the abnormal vertebra. The SIR of the mean signal intensity measured on opposed-phase to mean signal intensity measured on in-phase images was measured and recorded. RESULTS: The studied population included 30 patients, in whom 58 vertebrae were accessed, which included 38 dorsal, 18 lumbar, 1 sacral, and 1 cervical. Out of 58 vertebrae, 46 (79%) were malignant and 12 (20%) were benign. The mean CSI/SIR of malignant lesions was 0.96 and the mean SIR of benign lesions was 0.76. CONCLUSIONS: Conventional MRI sequences cannot always differentiate between benign and malignant lesions. So newer sequences like CSI have been developed. CSI SIR can be used as a new tool in differentiating benign osteoporotic and malignant vertebral marrow lesions.