Median Cubital Vein Traveling Deep to the Bicipital Aponeurosis: Anatomical Description With Application to Venipuncture and Vascular Access in the Cubital Fossa.

Knowledge of anatomical variations can aid the clinical practitioner in avoiding iatrogenic injury during invasive procedures. Here, we present an unusual finding of the median cubital vein and its relationship with bicipital aponeurosis. This case and relevant reports from the literature are reviewed. Physicians or other health care providers who perform procedures in the cubital fossa, such as venipuncture or vascular access, should be aware of such an anatomical variation.

TRACEBACK: Testing of Historical Tubo-Ovarian Cancer Patients for Hereditary Risk Genes as a Cancer Prevention Strategy in Family Members.

PURPOSE: Tubo-ovarian cancer (TOC) is a sentinel cancer for BRCA1 and BRCA2 pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed. We assessed the feasibility of detecting PVs in this population to enable genetic risk reduction in relatives. PATIENTS AND METHODS: In this pilot study, deceased probands were ascertained from research cohort studies, identification by a relative, and gynecologic oncology clinics. DNA was extracted from archival tissue or stored blood for panel sequencing of 10 risk-associated genes. Testing of deceased probands ascertained through clinic records was performed with a consent waiver. RESULTS: We identified 85 PVs in 84 of 787 (11%) probands. Familial contacts of 39 of 60 (65%) deceased probands with an identified recipient (60 of 84; 71%) have received a written notification of results, with follow-up verbal contact made in 85% (33 of 39). A minority of families (n = 4) were already aware of the PV. For many (29 of 33; 88%), the genetic result provided new information and referral to a genetic service was accepted in most cases (66%; 19 of 29). Those who declined referral (4 of 29) were all male next of kin whose family member had died more than 10 years before. CONCLUSION: We overcame ethical and logistic challenges to demonstrate that retrospective genetic testing to identify PVs in previously untested deceased probands with TOC is feasible. Understanding reasons for a family member's decision to accept or decline a referral will be important for guiding future TRACEBACK projects.

Molecular Targets of Triple-Negative Breast Cancer: Where Do We Stand?

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer. Due to its heterogeneity and lack of hormone receptor expression, this subtype is more likely to metastasize and resist treatment attempts than are other forms of breast cancer. Due to the absence of targetable receptors, chemotherapy and breast conserving surgery have been the predominant treatment options for patients. However, resistance to chemotherapy and local recurrence of the tumors is frequent. Emerging immunotherapies have begun to change treatment plans for patients diagnosed with TNBC. In this review, we discuss the various immune pathways identified in TNBC and the role they play as targets for new potential treatment choices. Various therapeutic options that inhibit key pathways in cellular growth cycles, DNA repair mechanisms, epithelial mesenchymal transition, and immunosuppression have been shown to improve survival in patients with this disease. With promising results thus far, continued studies of immunotherapy and neoadjuvant therapy options for TNBC are likely to alter the treatment course for these diagnoses in the future.

Split Azygos Vein: A Case Report.

The azygos venous system, which comprises the azygos, hemiazygos, and accessory hemiazygos veins, assists in blood drainage into the superior vena cava (SVC) from the thoracic cage and portions of the posterior mediastinum. Routine dissection of a fresh-frozen cadaveric specimen revealed a split azygos vein. The azygos vein branched off the inferior vena cava (IVC) at the level of the second lumbar vertebra as a single trunk and then split into two tributaries after forming a venous plexus. The right side of this system drained into the SVC and, inferiorly, the collective system drained into the IVC. Variant forms in the venous system, especially the vena cavae, are prone to dilation and tortuosity, leading to an increased likelihood of injury. Knowledge of the anatomical variations of the azygos vein is important for surgeons who use an anterior approach to the spine for diverse procedures.

Safety and immunogenicity of a four-component meningococcal group B vaccine (4CMenB) and a quadrivalent meningococcal group ACWY conjugate vaccine administered concomitantly in healthy laboratory workers.

Safety precautions for laboratory staff working with meningococci should primarily rely on laboratory procedures preventing exposure to aerosols containing viable meningococci. Despite this, vaccination is a key component of protection in the occupational setting. In the UK in 2009, there were no licensed vaccines for meningococcal capsular group B or conjugate vaccines for capsular groups A, C, W and Y. We therefore undertook a Phase II trial in laboratory workers to investigate the safety and immunogenicity of a four component group B vaccine (4CMenB) and a quadrivalent group A, C, W and Y conjugate vaccine (ACWY-CRM). Enrolment was open to staff aged 18-65 years at the Public Health Laboratory, Manchester who may have had a potential occupational exposure risk to meningococci. 4CMenB was administered at 0, 2 and 6 months in the non-dominant arm and ACWY-CRM concomitantly at 0 months in the dominant arm. Pre- and post-vaccination blood samples were taken and analysed by the serum bactericidal antibody (SBA) assay against A, C, W and Y strains and a panel of seven diverse group B strains. Diary cards were used to record any local and systemic reactions following each vaccination. In total, 38 staff were enrolled and received initial vaccinations with 31 completing the trial per protocol. Both vaccines were proven safe, with local reactogenicity being more commonly reported following 4CMenB than ACWY-CRM. High proportions of subjects had putative protective SBA titres pre-vaccination, with 61-84 and 61-87% protected against A, C, W and Y strains and diverse MenB strains, respectively. Post-vaccination, SBA titres increased with 95-100 and 90-100% of subjects with protective SBA titres against A, C, W and Y strains and diverse MenB strains, respectively. These data suggest that 4CMenB and ACWY-CRM are safe when administered concomitantly and have the potential to enhance protection for laboratory workers. www.clinicaltrials.gov identifier: NCT00962624.

Antibody concentrations against the infecting serotype in vaccinated and unvaccinated children with invasive pneumococcal disease in the United Kingdom, 2006-2013.

BACKGROUND: This study aimed to estimate, following invasive pneumococcal disease (IPD), the proportion of children with protective immunoglobulin G (IgG) concentrations against the infecting serotype compared with other vaccine serotypes, and to assess risk of recurrent IPD. METHODS: Pneumococcal antibody concentrations were available for 413 children with vaccine-type IPD diagnosed during 2006-2013. We compared serotype-specific IgG concentrations against the infecting vs other vaccine serotypes, after adjusting for confounders such as age using multilevel analyses. RESULTS: After IPD, a higher proportion of vaccine-naive children had IgG concentrations ≥0.35 µg/mL against their infecting serotype than other vaccine serotypes (51% vs 36%; P < .001). In contrast, among children immunized with pneumococcal conjugate vaccine (PCV) both before and after IPD, the proportion with IgG concentrations ≥0.35 µg/mL against the infecting serotype was lower compared with other vaccine serotypes (71% vs 98%; P < .001). These children also had lower IgG geometric mean concentrations (GMCs) against the infecting serotype (2.22 µg/mL) vs other vaccine serotypes (15.64 µg/mL) in multilevel models (IgG GMC ratio, 0.24; 95% confidence interval, .18-.32), although their IgG GMC was higher compared with vaccine-naive children. Vaccinated children with IgG concentrations <0.35 µg/mL against their infecting serotype generally remained unresponsive despite further vaccine doses. However, recurrent IPD with the same infecting serotype was rare (7/3030 children [0.2%]) and not associated with unresponsiveness. CONCLUSIONS: Vaccination with PCV before and/or after IPD was associated with lower IgG concentrations against the infecting serotype compared with other vaccine serotypes, but recurrent IPD was rare. Further studies are needed to understand this phenomenon in immunized children.

Evaluation of the safety and immunogenicity in United Kingdom laboratory workers of a combined Haemophilus influenzae type b and meningococcal capsular group C conjugate vaccine.

BACKGROUND: Although a combined Haemophilus influenzae type b (Hib)/meningococcal capsular group C (MenC) conjugate vaccine with a tetanus toxoid carrier protein (Hib/MenC-TT) is not licensed for use in those above 2 years of age due to lack of data on safety and efficacy, certain patient groups at high risk of MenC and/or Hib disease are recommended to receive it. Laboratory workers working with Hib and/or MenC cultures may be at a potentially increased risk of acquiring infectious diseases and vaccination is therefore an important safety consideration. We undertook a clinical trial to investigate the safety and immunogenicity of Hib/MenC-TT vaccine in this cohort. METHODS: A total of 33 subjects were recruited to the trial, all of whom were vaccinated. Serology was completed on samples taken at baseline and four weeks following vaccination to determine MenC specific IgG, MenC serum bactericidal antibody (SBA), anti-Hib polyribosylribitol phosphate (PRP) IgG and anti-tetanus toxoid IgG responses. RESULTS: At baseline, high proportions of subjects had protective antibody concentrations against MenC, Hib and tetanus due to previous vaccination and/or natural exposure. Vaccination induced > 3, 10 and 220 fold increases in geometric mean concentrations for MenC SBA, anti-tetanus toxoid IgG and anti-Hib PRP IgG, respectively. Following vaccination, 97% of subjects had putative protective SBA titres ≥ 8, 100% had short term protective anti-Hib PRP IgG concentrations ≥ 0.15 µg/mL and 97% had protective anti-tetanus toxoid concentrations ≥ 0.1 IU/mL. No safety concerns were reported with minor local reactions being reported by 21% of subjects. CONCLUSIONS: Immunological responses determined in this trial are likely a combination of primary and secondary responses due to previous vaccination and natural exposure. Subjects were a representative cross-section of laboratory workers, enabling us to conclude that a single dose of Hib/MenC-TT was safe and immunogenic in healthy adults providing the evidence that this vaccine may be used for providing protection in an occupational setting.

Phase variation mediates reductions in expression of surface proteins during persistent meningococcal carriage.

Asymptomatic and persistent colonization of the upper respiratory tract by Neisseria meningitidis occurs despite elicitation of adaptive immune responses against surface antigens. A putative mechanism for facilitating host persistence of this bacterial commensal and pathogen is alterations in expression of surface antigens by simple sequence repeat (SSR)-mediated phase variation. We investigated how often phase variation occurs during persistent carriage by analyzing the SSRs of eight loci in multiple isolates from 21 carriers representative of 1 to 6 months carriage. Alterations in repeat number were detected by a GeneScan analysis and occurred at 0.06 mutations/gene/month of carriage. The expression states were determined by Western blotting and two genes, fetA and nadA, exhibited trends toward low expression states. A critical finding from our unique examination of combinatorial expression states, "phasotypes," was for significant reductions in expression of multiple phase-variable surface proteins during persistent carriage of some strains. The immune responses in these carriers were examined by measuring variant-specific PorA IgG antibodies, capsular group Y IgG antibodies and serum bactericidal activity in concomitant serum samples. Persistent carriage was associated with high levels of specific IgG antibodies and serum bactericidal activity while recent strain acquisition correlated with a significant induction of antibodies. We conclude that phase-variable genes are driven into lower expression states during long-term persistent meningococcal carriage, in part due to continuous exposure to antibody-mediated selection, suggesting localized hypermutation has evolved to facilitate host persistence.

Immunity to tetanus and diphtheria in the UK in 2009.

INTRODUCTION: This study aimed to estimate the immunity of the UK population to tetanus and diphtheria, including the potential impact of new glycoconjugatate vaccines, and the addition of diphtheria to the school leaver booster in 1994. METHODS: Residual sera (n=2697) collected in England in 2009/10 were selected from 18 age groups and tested for tetanus and diphtheria antibody. Results were standardised by testing a panel of sera (n=150) to enable comparison with a previously (1996) published serosurvey. Data were then standardised to the UK population. RESULTS: In 2009, 83% of the UK population were protected (≥0.1 IU/mL) against tetanus compared to 76% in 1996 (p=0.079), and 75% had at least basic protection against diphtheria (≥0.01 IU/mL) in 2009 compared to 60% in 1996 (p<0.001). Higher antibody levels were observed in those aged 1-3 years in 2009 compared to 1996 for both tetanus and diphtheria. Higher diphtheria immunity was observed in those aged 16-34 years in 2009 compared to 1996 (geometric mean concentration [GMC] 0.15 IU/mL vs. 0.03 IU/mL, p<0.001). Age groups with the largest proportion of susceptible individuals to both tetanus and diphtheria in 2009 were <1 year old (>29% susceptible), 45-69 years (>20% susceptible) and 70+ years (>32% susceptible). Low immunity was observed in those aged 10-11 years (>19% susceptible), between the scheduled preschool and school leaver booster administration. DISCUSSION: The current schedule appears to induce protective levels; increases in the proportions protected/GMCs were observed for the ages receiving vaccinations according to UK policy. Glycoconjugate vaccines appear to have increased immunity, in particular for diphtheria, in preschool age groups. Diphtheria immunity in teenagers and young adults has increased as a result of the addition of diphtheria to the school leaver booster. However, currently older adults remain susceptible, without any further opportunities for immunisations planned according to the present schedule.

Scedosporium apiospermum keratomycosis in a dog.

A 6-year-old male castrated Norfolk Terrier dog was examined following a 21-day history of an increasingly painful eye. Examination revealed marked blepharospasm and purulent ocular discharge associated with an ulcerative keratitis. There was panstromal corneal opacity with raised gray to white lesions. Corneal cytology demonstrated branching septate fungal hyphae identified by polymerase chain reaction as Scedosporium apiospermum. Treatment with topical 1% voriconazole solution was successful in resolving the keratomycosis.

FT-Raman spectroscopic analysis of pigments from an Augustinian friary.

The Raman spectroscopic analysis of several stone samples with applied red pigments obtained from an archaeological excavation of an Augustinian friary discovered during the construction of an extension to Hull Magistrates Court in 1994 has revealed a surprising diversity of composition. Cinnabar, red lead and haematite have all been identified alone or in admixture; the cinnabar is exceptional in that it has only been found heavily adulterated with red ochre and red lead, as the other two pigments are found alone. There are signatures of limewash putty, which has been applied to the stone substrate prior to the painting, which is characteristic of the Roman method of wall painting, and there are no traces of gypsum found in the specimens studied. This evidence indicates an early mediaeval method of stone decoration.

Raman spectroscopic detection of biomolecular markers from Antarctic materials: evaluation for putative Martian habitats.

The vital UV-protective and photosynthetic pigments of cyanobacteria and lichens (microbial symbioses) that dominate primary production in Antarctic desert ecosystems auto-fluoresce at short-wavelengths. A long wavelength (1064 nm) near infra-red laser has been used for non-intrusive Raman spectroscopic analysis of their ecologically significant compounds. There is now much interest in the construction of portable Raman systems for the analysis of cyanobacterial and lichen communities in the field; to this extent, Raman spectra obtained with laboratory-based systems operating at wavelengths of 852 and 1064 nm have been evaluated for potential fieldwork applications of miniaturised units. Selected test specimens of the cyanobacterial Nostoc commune, epilithic lichens Acarospora chlorophana, Xanthoria elegans and Caloplaca saxicola and the endolithic Chroococcidiopsis from Antarctic sites have been examined in the present study. Although some organisms gave useable Raman spectra with short-wavelength lasers, 1064 nm was the only excitation that was consistently excellent for all organisms. We conclude that a 1064 nm Raman spectrometer, miniaturised using an InGaAs detector, is the optimal instrument for in situ studies of pigmented communities at the limits of life on Earth. This has practical potential for the quest for biomolecules residual from any former surface or subsurface life on Mars.