Risk factors for bacterial infection to cause sensorineural hearing loss in eosinophilic otitis media

ObjectiveEosinophilic otitis media (EOM) is an intractable type of otitis media in which sensorineural hearing loss (SNHL) progresses over time. Clinically, bacterial infection complicates the course of EOM, making it challenging to control otorrhea/middle ear effusion (MEE) from infected ears, and accelerates the progression of SNHL. In this study, we focused on infection, one of the risk factors for SNHL in EOM, and analyzed factors associated with it.MethodsIn this cohort study, we evaluated 144 ears of 72 patients diagnosed with bilateral EOM. Patients visited our hospital once every 1–3 months and received intratympanic or systematic administration of steroids when otorrhea/MEE was observed. Several investigations, including blood tests, otorrhea/MEE cytology, bacterial culture tests, and respiratory function tests, were performed. In the otorrhea/MEE cytology, the leukocyte fraction was measured.ResultsTwo risk factors for SNHL in EOM were middle ear mucosal thickening (p <0.01) and infection (p <0.05). Compared to the group with <40% neutrophils in otorrhea/MEE samples, groups with 40–70% and ≥70% neutrophils had a significantly higher bone conduction hearing level (p <0.01, p <0.05, respectively). Two risk factors associated with the occurrence of infection in EOM were tympanic membrane (TM) perforation (p <0.01) and the coincidence of otorrhea/MEE and rhinorrhea in bacterial culture test results (p <0.001). A positive correlation was observed between TM perforation and infection (p <0.001). Our analysis of the relationship between the frequency of intratympanic corticosteroids administration and the time-period until the occurrence of TM perforation showed that >4 intratympanic administrations/year significantly increased the risk of perforation (p<0.001). Pseudomonas aeruginosa was isolated from otorrhea/MEE samples, while Pseudomonas aeruginosa and fungi, detected in cultures of rhinorrhea samples, were significantly related to the deterioration of bone conduction hearing levels.ConclusionThe risk factors associated with the occurrence of infection in patients with EOM were TM perforation and the coincidence of otorrhea/MEE and rhinorrhea in bacterial culture test results. Since TM perforation is likely to occur even due to intratympanic corticosteroids administration, it is necessary to confirm whether the frequency of treatment is appropriate and try a less invasive technique of administration. Furthermore, Pseudomonas aeruginosa infection poses a high risk for the development of SNHL, and clinicians should be alert to this possibility, even if the bacteria were identified only in cultures of rhinorrhea samples.     

Comparative analysis of different enzyme immunoassays for assessment of phosphatidylserine-dependent antiprothrombin antibodies

Phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) were strongly correlated with the presence of lupus anticoagulant showing a high specificity for the diagnosis of antiphospholipid syndrome. However, the main criticism for the clinical applicability of aPS/PT testing is the lack of reproducibility of the results among laboratories. In this study, we measured IgG and IgM aPS/PT using our original in-house enzyme-linked immunosorbent assays (ELISA) and commercial ELISA kits to assess the assay performance and to evaluate the accuracy of aPS/PT results. The study included 111 plasma samples collected from patients and stored at our laboratory for aPS/PT assessment. Sixty-one samples were tested for IgG aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgG ELISA kit (INOVA Diagnostics, Inc., USA). Fifty samples were evaluated for IgM aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgM ELISA kit (INOVA Diagnostics). Ninety-eight percent of samples yielded concordant results for IgG aPS/PT and 82 % for IgM aPS/PT. There was an excellent agreement between the IgG aPS/PT assays (Cohen κ = 0.962) and moderate agreement between the IgM aPS/PT assays (κ = 0.597). Statistically significant correlations in the aPS/PT results were obtained from both IgG and IgM aPS/PT assays (r = 0.749, r = 0.622, p < 0.001, respectively). In conclusion, IgG and IgM detection by ELISA is accurate. The performance of aPS/PT is reliable, and concordant results can be obtained using different ELISA methods.     

The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts

GeroScience - The rs1333049 (G/C) polymorphism located on chromosome 9p21.3 is a candidate to influence extreme longevity owing to its association with age-related diseases, notably coronary artery...     

A GCH1 haplotype confers sex‐specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia

GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21–5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry. Am. J. Hematol. 89:187–193, 2014. © 2013 Wiley Periodicals, Inc.     

Imaging flow cytometry for automated detection of hypoxia‐induced erythrocyte shape change in sickle cell disease

In preclinical and early phase pharmacologic trials in sickle cell disease, the percentage of sickled erythrocytes after deoxygenation, an ex vivo functional sickling assay, has been used as a measure of a patient's disease outcome. We developed a new sickle imaging flow cytometry assay (SIFCA) and investigated its application. To perform the SIFCA, peripheral blood was diluted, deoxygenated (2% oxygen) for 2 hr, fixed, and analyzed using imaging flow cytometry. We developed a software algorithm that correctly classified investigator tagged “sickled” and “normal” erythrocyte morphology with a sensitivity of 100% and a specificity of 99.1%. The percentage of sickled cells as measured by SIFCA correlated strongly with the percentage of sickle cell anemia blood in experimentally admixed samples (R = 0.98, P ≤ 0.001), negatively with fetal hemoglobin (HbF) levels (R = ?0.558, P = 0.027), negatively with pH (R = ?0.688, P = 0.026), negatively with pretreatment with the antisickling agent, Aes‐103 (5‐hydroxymethyl‐2‐furfural) (R = ?0.766, P = 0.002), and positively with the presence of long intracellular fibers as visualized by transmission electron microscopy (R = 0.799, P = 0.002). This study shows proof of principle that the automated, operator‐independent SIFCA is associated with predictable physiologic and clinical parameters and is altered by the putative antisickling agent, Aes‐103. SIFCA is a new method that may be useful in sickle cell drug development. Am. J. Hematol. 89:598–603, 2014. © 2014 Wiley Periodicals, Inc.