Endogenous Endophthalmitis from Urinary Tract Infection Caused by Group B Streptococcus: A Case Report.

We present a case of endogenous endophthalmitis with urinary tract infection (UTI) caused by group B Streptococcus (GBS). An 86-year-old female initially presented with ocular pain and sudden visual disturbance of the left eye. The patient did not complain of other symptoms and had no history of recent ocular surgery or trauma. Endogenous endophthalmitis was clinically diagnosed based on ophthalmic examination, history, and lab results showing systemic infection. A few days later, GBS was identified in her aqueous humor, blood, and urine cultures. Intravitreal ceftazidime and vancomycin injections, as well as fortified ceftazidime and vancomycin eye drops, were used immediately after clinical diagnosis. However, the symptoms worsened despite repeated intravitreal injections, so evisceration was performed. Endogenous endophthalmitis caused by GBS is very virulent and may present without evident systemic symptoms. The early recognition of the disease and systemic work up, followed by prompt treatment, is necessary.

Ophthalmic findings in Cohen syndrome patient without subjective ophthalmic complaints: A case report.

RATIONALE: Cohen syndrome is a rare genetic disorder that can cause various symptoms, including ophthalmic manifestations that can significantly impact a patient's visual health and quality of life. PATIENT CONCERNS: We present the case of a 12-year-old boy diagnosed with Cohen syndrome who exhibited retinal degeneration and macular edema but could not express ophthalmic symptoms due to a developmental disability. DIAGNOSES: The patient was diagnosed with Cohen syndrome by a heterozygous mutation in the VPS13B gene by whole exome sequencing and referred to ophthalmology for an ophthalmic examination. INTERVENTION: Ophthalmologic tests, including visual acuity, intraocular pressure, slit lamp examination, fundus photography, and optical coherence tomography, were performed. OUTCOMES: Visual acuity and intraocular pressure were not measured due to poor cooperation, and no abnormal findings were observed on the slit lamp examination. However, peripheral retinal degeneration was observed in the fundus examination, and cystoid macular edema was observed in both eyes on optical coherence tomography. LESSONS: Regular ophthalmologic examination is important for patients with Cohen syndrome, especially those with developmental disabilities who may not be able to express their symptoms. Clinicians should be aware of the potential ophthalmologic manifestations of Cohen syndrome and the importance of timely diagnosis and management.

A 37-40 GHz 6-Bits Switched-Filter Phase Shifter Using 150 nm GaN HEMT.

In this paper, we present a 6-bit phase shifter designed and fabricated using the 150 nm GaN HEMT process. The designed phase shifter operates within the n260 (37~40 GHz) band, as specified in the 5G NR standard, and employs the structure of a switched-filter phase shifter. By serially connecting six single-bit phase shifters, ranging from 180° to 5.625°, the designed phase shifter achieves a phase range of 360°. The fabricated phase shifter exhibits a minimum insertion loss of 5 dB and an RMS phase error of less than 5.36° within the 37 to 40 GHz. This phase shifter is intended for seamless integration with high-power RF circuits.

Anesthetic Considerations in Patients With Achondroplasia.

Anesthetic management of achondroplastic patients warrants special anatomical and physiological considerations due to significant variations in the airway as well as the spine in regional techniques. In this report, we present the case of a 30-year-old morbidly obese male with achondroplasia, end-stage renal disease (ESRD) on hemodialysis, and renal osteodystrophy, who was scheduled for incision and drainage of a rectal abscess. Preoperative evaluation revealed Mallampati IV airway with a short neck and a scoliotic spine with possible atlantoaxial instability.

Fusions involving BCOR and CREBBP are rare events in infiltrating glioma.

BCOR has been recognized as a recurrently altered gene in a subset of pediatric tumors of the central nervous system (CNS). Here, we describe a novel BCOR-CREBBP fusion event in a case of pediatric infiltrating astrocytoma and further probe the frequency of related fusion events in CNS tumors. We analyzed biopsy samples taken from a 15-year-old male with an aggressive, unresectable and multifocal infiltrating astrocytoma. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing. In the index case, the fused BCOR-CREBBP transcript comprises exons 1-4 of BCOR and exon 31 of CREBBP. The fused gene thus retains the Bcl6 interaction domain of BCOR while eliminating the domain that has been shown to interact with the polycomb group protein PCGF1. The fusion event was validated by FISH and reverse transcriptase PCR. An additional set of 177 pediatric and adult primary CNS tumors were assessed via FISH for BCOR break apart events, all of which were negative. An additional 509 adult lower grade infiltrating gliomas from the publicly available TCGA dataset were screened for BCOR or CREBBP fusions. In this set, one case was found to harbor a CREBBP-GOLGA6L2 fusion and one case a CREBBP-SRRM2 fusion. In a third patient, both BCOR-L3MBTL2 and EP300-BCOR fusions were seen. Of particular interest to this study, EP300 is a paralog of CREBBP and the breakpoint seen involves a similar region of the gene to that of the index case; however, the resultant transcript is predicted to be completely distinct. While this gene fusion may play an oncogenic role through the loss of tumor suppressor functions of BCOR and CREBBP, further screening over larger cohorts and functional validation is needed to determine the degree to which this or similar fusions are recurrent and to elucidate their oncogenic potential.

A 6-year Prospective, Observational, Multi-Center Post-Marketing Surveillance of the Safety of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis (Tdap) Vaccine in Korea.

BACKGROUND: Incidence of whooping cough is increasing in Korea. Since 2011, occurrence among adolescents and adults has risen putting vulnerable neonates at risk. National immunization guidelines now include Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination during pregnancy and as a cocooning strategy (i.e., vaccinating adults and adolescents in contact with neonates). This study assessed post-marketing Tdap (Boostrix®, GSK, Belgium) vaccine safety in subjects ≥ 10 years. METHODS: This open, non-comparative multi-center study was conducted over six years at 10 hospitals in Korea. Subjects received Tdap in normal clinical practice according to local prescribing information. All adverse events (AEs) were recorded, classified as expected or unexpected, and severity and relationship to Tdap were assessed. RESULTS: The analysis included 672 Korean subjects (mean age, 44 years; range, 11-81), 451 were women and 211 were pregnant. Ninety subjects experienced 124 AEs (incidence 13.39%) of which six were serious AEs (SAEs) assessed as not related to vaccination, and 51 were non-SAEs related to vaccination (mostly administration site reactions). Overall 65/124 AEs were unexpected; the most common were 14 constipation, 5 dyspepsia, 4 common cold and 4 premature labor cases. One case of common cold was assessed as possibly related to vaccination. Pregnancy outcome was 'live infant, no apparent congenital anomaly' in 195 subjects (92.42%) or 'lost to follow-up' in 16 subjects. CONCLUSION: Tdap administration to Korean subjects ≥ 10 years, including pregnant women, for the prevention of diphtheria, tetanus and pertussis was shown to have a well-tolerated safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01929291.

Post-marketing surveillance to assess the safety and tolerability of a combined diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine (DTaP-IPV) in Korean children.

Infanrix-IPV (GSK, Belgium) is a diphtheria, tetanus, acellular pertussis, and inactivated poliovirus combination vaccine (DTaP-IPV) licensed in many countries including Korea. In accordance with Korean regulations, we conducted a post-marketing surveillance (PMS) to evaluate the safety of DTaP-IPV administered to Korean children in routine immunization schedules. Children aged <7 years receiving at least one dose of DTaP-IPV either as part of a primary (3-dose) vaccination series or as a subsequent booster were enrolled. Adverse events (AEs), adverse drug reactions (ADRs) and serious AEs (SAEs) were recorded after each dose during the 30-day post-vaccination follow-up period. Among a total of 639 children, 289 subjects (45.2%) experienced AEs, mostly (79.2%) assessed as being unlikely to be related to the vaccination. ADRs were reported in 13.0% of subjects. Fever was the most commonly reported expected AE (11.9% of subjects) and also the most commonly reported expected ADR (8.5% of subjects). No obvious association between AE incidence and vaccine dose sequence was apparent. An unexpected AE was seen in 32.9% of children, and unexpected ADRs were far less common (1.9%). Thirty-four SAEs were recorded in 26 subjects (4.1%), in two of whom a causal association with the vaccine could not be excluded, although both resolved quickly. Data from this PMS indicate that DTaP-IPV has an acceptable safety profile when given to Korean children in accordance with local prescribing recommendations in routine childhood immunization. ClinicalTrials.gov identifier: NCT01568060.

Uropathogenic Escherichia coli invades bladder epithelial cells by activating kinase networks in host cells.

Uropathogenic Escherichia coli (UPEC) is the causative bacterium in most urinary tract infections (UTIs). UPEC cells adhere to and invade bladder epithelial cells (BECs) and cause uropathogenicity. Invading UPEC cells may encounter one of several fates, including degradation in the lysosome, expulsion to the extracellular milieu for clearance, or survival as an intracellular bacterial community and quiescent intracellular reservoir that can cause later infections. Here we considered the possibility that UPEC cells secrete factors that activate specific host cell signaling networks to facilitate the UPEC invasion of BECs. Using GFP-based reporters and Western blot analysis, we found that the representative human cystitis isolate E. coli UTI89 and its derivative UTI89ΔFimH, which does not bind to BECs, equally activate phosphatidylinositol 4,5-bisphosphate 3-OH kinase (PI3K), Akt kinase, and mTOR complex (mTORC) 1 and 2 in BECs. We also found that conditioned medium taken from UTI89 and UTI89ΔFimH cultures similarly activates epidermal growth factor receptor (EGFR), PI3K, Akt, and mTORC and that inhibition of EGFR and mTORC2, but not mTORC1, abrogates UTI89 invasion in vitro and in animal models of UTI. Our results reveal a key molecular mechanism of UPEC invasion and the host cells it targets, insights that may have therapeutic utility for managing the ever-increasing number of persistent and chronic UTIs.

A proangiogenic signaling axis in myeloid cells promotes malignant progression of glioma.

Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) as a key upstream regulator of KDR activation during myeloid differentiation. Deficiency of ID2 in BMDCs led to downregulation of KDR, suppression of proangiogenic myeloid cells, and prevention of low-grade to high-grade transition. Tumor-secreted TGF-ß and granulocyte-macrophage CSF (GM-CSF) enhanced the KDR/ID2 signaling axis in BMDCs. Our results suggest that modulation of KDR/ID2 signaling may restrict tumor-associated myeloid cells and could potentially be a therapeutic strategy for preventing transformation of premalignant gliomas.

CSF hydrothorax without intrathoracic catheter migration in children with ventriculoperitoneal shunt.

BACKGROUND: Thoracic complications of ventriculoperitoneal (VP) shunts have been extensively reported in the literature. Cerebrospinal fluid (CSF) hydrothorax without catheter migration, however, has been rarely described and poorly understood. CASE DESCRIPTION: We describe development of pleural effusion and respiratory distress in a 3-year-old boy with no evidence of VP shunt catheter displacement on plain radiograph and stable ventricle size on rapid sequence magnetic resonance imaging (MRI) brain. Chest X-ray revealed complete opacity of right hemithorax. Pleural effusion was consistent with transudate. Beta-2 transferrin returned positive. The patient underwent externalization of VP shunt, and upon resolution of effusion, re-internalization with new distal shunt catheter. A literature review of CSF hydrothorax in children without intrathoracic shunt migration was performed. Eleven cases were identified in the English literature. Age at VP shunt placement ranged from birth to 8 years of age. Interval from VP shunt placement to CSF hydrothorax ranged from 1.5 months to 5 years. History of shunt revision was reported in two cases. Presenting symptoms also included ascites and inguinal hernia or hydrocele. Reported diagnostic studies consist of CSF culture, radionuclide shuntogram, beta-2 transferrin, and beta-trace protein. Laterality of the VP shunt and development of pleural effusion were predominantly right sided. Definitive surgical treatment included VA shunt, repositioning of the peritoneal catheter, and endoscopic choroid plexus coagulation. CONCLUSION: CSF hydrothorax is a rare thoracic complication of VP shunt placement with no radiographic evidence of shunt migration or malfunction. Postulated mechanisms include limited peritoneal capacity to resorb CSF in children and microscopic communications present in congenital diaphragmatic hiatuses.

Low-dose intrathecal fluorescein and etiology-based graft choice in endoscopic endonasal closure of CSF leaks.

OBJECTIVE: Skull base cerebrospinal fluid (CSF) leaks of various etiologies are increasingly repaired through the natural corridor using an endoscopic endonasal approach. Characteristics of the skull base defect significantly correlate with etiology, which should be ascertained to guide surgical management. The objectives of this study were to assess the long-term outcomes of patients that underwent endoscopic endonasal repair of CSF leak using low-dose intrathecal fluorescein (ITF) and an etiology-based algorithm for multi-layer graft closure. METHODS: Patients were divided into 4 groups: A--congenital, B--post-traumatic, C--post-endonasal surgery, D--post-craniotomy. Low-dose ITF was utilized in all case series. Long-term clinical follow-up data, including perioperative complications associated with the use of intrathecal fluorescein and leak closure rates, were obtained retrospectively. Endoscopic visualization of fluorescein-stained CSF as well as the method of skull base closure and graft material is detailed. RESULTS: We identified a total of 41 patients (N=24 in Group A, N=4 in Group B, N=12 in Group C and N=1 in Group D) that underwent 50 CSF leak repairs using the endoscopic endonasal approach with an average follow-up of 31.6 months. Nine patients (21.9%) had undergone a previous attempt at CSF leak repair. Lumbar drain was used intraoperatively in 26 patients (63.4%) and kept in place for an average duration of 3.25 days. ITF successfully identified the site of leak in 80.5% of cases regardless of etiology. Leaks were successfully closed in 92% of patients. One patient (2.4%) experienced transient leg weakness following lumbar drain placement. Another patient (2.4%) developed hydrocephalus requiring a ventriculoperitoneal shunt. CONCLUSION: Low-dose ITF is a safe and useful adjunct to endoscopic endonasal repair of CSF leaks with minimal complications and successful localization of the leak in approximately 80%. An etiology-based approach to graft choice and duration of lumbar drain placement in CSF leak repair may optimize closure rates.

Resection of glioma in an fMRI-defined "split" Broca's area.

Gross total resection of gliomas can be limited by the involvement of tumor in eloquent areas. Moreover, lesions can impart cortical reorganization and make the precise determination of hemispheric dominance and localization of language function even more difficult. Preoperative mapping with functional magnetic resonance imaging (fMRI), intraoperative imaging modalities, and intraoperative direct cortical stimulation enable surgeons to map the functional topography of the brain in relation to the tumor and perform a safe maximal resection. In this report, we present a patient with left frontal glioma of complex morphology, wherein the tumor was enveloped by Broca's area on fMRI. Intraoperative mapping and intraoperative magnetic resonance imaging (iMRI) allowed gross total resection of the tumor with preservation of language function and illustrate the utility of multiple contemporary modalities in the surgical management of low-grade gliomas located in eloquent cortices.

Oligodendrocyte progenitor cells promote neovascularization in glioma by disrupting the blood-brain barrier.

Enhanced platelet-derived growth factor (PDGF) signaling in glioma drives its development and progression. In this study, we define a unique role for stroma-derived PDGF signaling in maintaining tumor homeostasis within the glioma microenvironment. Large numbers of PDGF receptor-α (PDGFRα)-expressing stromal cells derived from oligodendrocytes progenitor cells (OPC) were discovered at the invasive front of high-grade gliomas, in which they exhibited a unique perivascular distribution. In PDGFRα-deficient host mice, in which orthotopic Gl261 tumors displayed reduced outgrowth, we found that tumor-associated blood vessels displayed smaller lumens and normalized vascular morphology, with tumors in host animals injected with the vascular imaging agent gadolinium also being enhanced less avidly by MRI. Notably, glioma-associated OPC promoted endothelial sprouting and tubule formation, in part by abrogating the inhibitory effect that perivascular astrocytes exert on vascular endothelial conjunctions. Stromal-derived PDGF-CC was crucial for the recruitment and activation of OPC, insofar as mice genetically deficient in PDGF-CC phenocopied the glioma/vascular defects observed in PDGFRα-deficient mice. Clinically, we showed that higher levels of PDGF-CC in glioma specimens were associated with more rapid disease recurrence and poorer overall survival. Our findings define a PDGFRα/PDGF-CC signaling axis within the glioma stromal microenvironment that contributes to vascular remodeling and aberrant tumor angiogenesis in the brain.

Adjuvant whole brain radiation following resection of brain metastases.

Brain metastasis is a common complication of systemic cancer and significant cause of suffering in oncology patients. Despite a plethora of available treatment modalities, the prognosis is poor with a median survival time of approximately one year. For patients with controlled systemic disease, good performance status, and a limited number of metastases, treatment typically entails surgical resection or radiosurgery, followed by whole brain radiotherapy (WBRT) to control microscopic disease. WBRT is known to control the progression of cancer in the brain, but it can also have toxic effects, particularly with regard to neurocognition. There is no consensus as to whether the benefit of WBRT outweighs the potential harm. We review the evidence related to the question of whether patients undergoing surgical resection of brain metastases should receive adjuvant WBRT.

Clinical, demographic, and medicolegal factors associated with geographic variation in inferior vena cava filter utilization: an interstate analysis.

OBJECTIVES: Geographic variability exists in the use of IVC filters (IVCF). We hypothesized that variation in IVCF use is incompletely explained by variation in the prevalence of deep-vein thrombosis (DVT) and pulmonary embolism (PE) and may result from different practice patterns regarding prophylactic IVCF use. We characterize geographic variation in IVCF use at the state level and evaluate its association with clinical factors, patient demographics, and the medicolegal environment. METHODS: Healthcare Cost and Utilization Project State Inpatient Database records were accessed to identify 230,445 IVCFs placed from 2006 to 2008 in 33 states. Similar queries were performed for DVT and PE. Additional state data were obtained from public sources. Analyses included descriptive statistics, Spearman Correlation (SC), Wilcoxon rank-sum test, and characterization of variability. RESULTS: Overall, IVCF use correlated with the prevalence of DVT (SC = 0.89, P < .01). States on the East coast have significantly greater rates of IVCF use per 100K (mean ± SD = 41.2 ± 16.7 vs 27.8 ± 11.1, P < .05) and greater rates of IVCF per DVT (20.2 ± 4.5% vs 15.2 ± 2.9%; P < .005), despite similar rates of DVT per 100K (198.1 ± 51.2 vs 177.7 ± 46.7, P = NS) compared with all other states. Overall, states with the greatest rate of IVCF per DVT were (in descending order): Rhode Island, New Jersey, Florida, New York, and West Virginia. Rates of detected PE per 100K in these states were not significantly different from all other states (95.6 ± 16.6 vs 90.4 ± 16.1, P = NS). In these states, a greater percentage of IVCF recipients were older than 85 (15.3% vs 11.8%; P < .01); fewer were pediatric (0.3% vs 0.7%; P < .05) or aged 45 to 64 (26.1% vs 32.4%; P < .001). There were no differences in patient sex, race, insurance type, hospital size, or teaching status. States with high rates of IVCF per DVT were noted to have significantly greater rates of paid malpractice claims per 100K (4.9 ± 2.51 vs 1.1 ± 0.8; P = .001), and annual general surgeon liability insurance premiums ($78,630 ± 34,822 vs $43,989 ± 17,794; P < .05). CONCLUSION: Variation in IVCF use is incompletely explained by clinical factors. High rates of IVCF per DVT in some states may represent increased use of prophylactic IVCF in states with litigious medicolegal environments.

Molecular diagnostics in paediatric glial tumours.

Glial tumours in children have distinct patterns of epigenetic alteration, chromosomal structure, and gene and protein expression that differentiate them from their histological counterparts in adults. Understanding paediatric gliomas at the molecular level provides important prognostic and therapeutic insights, such as which genetic alterations confer a favourable response to adjuvant therapy, or which signalling pathways might be amenable to specific molecularly targeted agents. For clinicians, the ultimate goal is to individualise therapeutic regimens on the basis of the molecular fingerprint of a particular tumour and the prognosis conferred by this profile. In this Review, we examine a series of studies of molecular and genomic analysis of glial tumours in children, and discuss the many clinical insights that these molecular features provide.

Angiopoietin-like protein 2, a chronic inflammatory mediator, is a new target induced by TGF-ß1 through a Smad3-dependent mechanism.

Angiopoietin-like protein 2 (Angptl2) levels are increased by obesity and obesity-related pathological conditions, and it is considered to be an important adipocyte-derived inflammatory mediator. In contrast, the multifunctional cytokine TGF-ß1 has been reported to be augmented in obesity of rodents and humans, but inhibits adipocyte differentiation in vitro. Here we demonstrate that TGF-ß1 induces expression of the Angptl2 gene through a Smad3-dependent pathway in RAW264.7 macrophage cells, primary peritoneal macrophages, and differentiated 3T3-L1 adipocytes. Transcriptional induction of the Angptl2 gene by TGF-ß1 was dependent on the Smad3 protein which binds to the Smad Binding Element (SBE) region located on the Angptl2 promoter. Macrophages with Smad3 knocked down by small interfering RNA showed reduction of TGF-ß1-induced Angptl2 expression. These findings may provide insight into the molecular mechanisms of the increased expression of Angptl2 and TGF-ß1 in obesity.

Factors contributing to ventriculostomy infection.

OBJECTIVE: Catheter-related infection remains a cause of morbidity in the use of external ventricular drains (EVDs). The aim of this retrospective single-center study was to assess the rate and factors related to ventriculostomy infections in the setting of the published literature. METHODS: Patients that underwent EVD placement in a single-center were retrospectively reviewed. Diagnosis, treatment, hospital course, and infection-related data were collected and analyzed in reference to ventriculitis rates. The protocols for EVD placement and maintenance were reviewed. RESULTS: Of 343 patients, 12 acquired an EVD infection. No significant differences existed between those with and without ventriculitis for age, sex, underlying diagnosis, or concomitant systemic infection. Although not significant, concomitant systemic infection existed in 4.7% of patients with ventriculitis versus 1.5% without. There was a significant difference in length of EVD placement in patients with ventriculitis (20.9 ± 15.3 days) versus those without (12.1 ± 18.2; P = 0.005). Coagulase-negative Staphylococcus and Staphylococcus aureus represented the most commonly associated pathogens. With an overall cumulative incidence of 3.5%, our rate compared favorably to the published literature (cumulative incidence 9.5%; range, 3.9%-23.2%). CONCLUSIONS: Catheter-related infection remains an important complication of EVD placement. Of factors evaluated, length of time of catheter placement has the most notable relationship to infection incidence, suggesting that early drain removal should be a goal whenever medically appropriate.