Case report: Exploring autosomal recessive woolly hair: genetic and scanning electron microscopic perspectives on a Japanese patient.

Woolly hair (WH) is a hair shaft anomaly characterized by tightly curled hair that typically stops growing at a few inches. Autosomal recessive WH (ARWH; OMIM no. 278150/604379/616760) has been reported to be caused by variants in genes coding lysophosphatidic acid receptor 6 (LPAR6), lipase H (LIPH), or keratin 25 (KRT25). In this study, we conducted a scanning electron microscopic (SEM) examination of the hair of a 3-year-old Japanese ARWH patient. The SEM revealed that her affected hair had an irregular and rough cuticle compared to her mother's hair. Many irregular small projections and longitudinal grooves were seen on the surface of the patient's hair shaft, and some free margins of the hair cortex were raised or serrated. Her hairs were oval-shaped on the cross-section. Mutation analysis revealed a homozygous pathogenic variant (c.736 T > A; Cys246Ser) in exon 6 in LIPH. In our clinic, we identified three additional cases with the homozygous Cys246Ser variant and one case with compound heterozygous variants in LIPH: Cys246Ser and c.671C > G (Pro224Arg). Consequently, genetic analyses, including genotype-phenotype correlation involving rare LIPH variants, have become more crucial in the Japanese population.

Multiple Blood Culture Sampling, Proper Antimicrobial Choice, and Adequate Dose in Definitive Therapy Supported by the Antimicrobial Stewardship Team Could Decrease 30-Day Sepsis Mortality Rates.

Objective: This study aimed to identify factors that should be focused on by the antimicrobial stewardship team for treating patients with sepsis, by investigating the mortality of patients with sepsis within 30 days and the mortality-related factors in our hospital over a 10-year period from the perspective of appropriate antimicrobial use. Methods: Factors associated with 30-day mortality were investigated using hierarchical multiple logistic regression in 1406 patients with pathogen-identified sepsis in Hirosaki University Hospital. These factors were clinical data, microbiological data, antimicrobials used in empiric and definitive therapies, presence/absence of ineffective use, underdosing as evaluated using Monte Carlo simulation, and practice of de-escalation. Results: The ineffective use of antimicrobials in empiric therapy and the underdosing and ineffective use in definitive therapy were significantly associated with 30-day mortality (odds ratio [OR] = 2.70, 3.72, and 3.65, respectively). Multiple blood culture sampling was inversely associated with these inappropriate antimicrobial uses. Every year, the 30-day mortality rate has been decreasing, in line with the increase in multiple blood culture sampling and de-escalation; the inappropriate use of antimicrobials has also decreased. Conclusion: Multiple blood culture sampling, proper choice of antimicrobial, and using an adequate dose in definitive therapy could decrease the 30-day mortality rate in patients with sepsis and these factors could be supported by the antimicrobial stewardship team.

Case report: A case of epidermolysis bullosa acquisita with IgG and IgM anti-basement membrane zone antibodies relapsed after COVID-19 mRNA vaccination.

We report a case of autoimmune bullous disease (AIBD) with IgG and IgM autoantibodies against epidermal basement membrane zone (BMZ), which showed recurrence of mucocutaneous lesions after coronavirus disease 2019 (COVID-19) mRNA vaccination. A 20-year-old Japanese woman with a 4-year history of epidermolysis bullosa acquisita (EBA) presented to our clinic. She noticed fever and rash on the same day and visited at our hospital 2 days later. Physical examination revealed blisters, erosions and erythema on the face, shoulder, back, upper arms, and lower lip. A skin biopsy from the forehead showed subepidermal blister. Direct immunofluorescence showed linear depositions of IgG, IgM, and C3c in the epidermal BMZ. By indirect immunofluorescence of 1M NaCl-split normal human skin, circulating IgG autoantibodies were bound to the dermal side of the split at 1:40 serum dilution, and circulating IgM antibodies were bound to the epidermal side of the spilt. After the increase of prednisolone dose to 15 mg/day, the mucocutaneous lesions resolved in a week. The present case is the first case of possible EBA with IgG and IgM anti-BMZ antibodies, in which the mucocutaneous lesions were recurred after COVID-19 mRNA vaccination. Clinicians should be aware that bullous pemphigoid-like AIBDs, including EBA and IgM pemphigoid, might be developed after COVID-19 mRNA vaccination.

Conventional and Kampo Medicine Treatment for Mild-to-moderate COVID-19: A Multicenter, Retrospective, Observational Study by the Integrative Management in Japan for Epidemic Disease (IMJEDI Study-observation).

Objective Patients in whom coronavirus disease 2019 (COVID-19) was suspected or confirmed between January 1, 2020, and October 31, 2021, were enrolled from Japanese hospitals in this multicenter, retrospective, observational study. Methods Data on the treatment administered (including conventional and Kampo medicine) and changes in common cold-like symptoms (such as fever, cough, sputum, dyspnea, fatigue, and diarrhea) were collected from their medical records. The primary outcome was the number of days without a fever (with a body temperature <37°C). The secondary outcomes were symptomatic relief and the worsening of illness, defined as the presence of a condition requiring oxygen inhalation. The outcomes of patients treated with and without Kampo medicine were compared. Patients We enrolled 962 patients, among whom 528 received conventional and Kampo treatment (Kampo group) and 434 received conventional treatment (non-Kampo group). Results Overall, after adjusting for the staging of COVID-19 and risk factors, there were no significant between-group differences in the symptoms or number of days being afebrile. After performing propensity score matching and restricting the included cases to those with confirmed COVID-19 who did not receive steroid administration and initiated treatment within 4 days from the onset, the risk of illness worsening was significantly lower in the Kampo group than in the non-Kampo group (odds ratio=0.113, 95% confidence interval: 0.014-0.928, p=0.0424). Conclusion Early Kampo treatment may suppress illness worsening risk in COVID-19 cases without steroid use. Further randomized controlled studies are needed to confirm the clinical benefit of Kampo medicine for COVID-19.

A Case of Anti-BP180-type Mucous Membrane Pemphigoid with IgG and IgA Autoantibodies Showing Distinct Reactivities.

Dear Editor, Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by erosive mucosal lesions mainly on the oral and ocular mucosae (1). We report a case of oral and ocular anti-BP180-type MMP with variable IgG and IgA reactivities and underlying dementia. An 84-year-old Japanese man presented with a 4-year history of erosions in the oral cavity and on the conjunctivae, with progressive vision impairment. The medical history included benign prostatic hyperplasia, cataract, sinusitis, and dementia. Physical examination revealed erosions and white atrophic scars along the gingival mucosa and on the hard palate (Figure 1, a, b). Conjunctival inflammation and corneal scarring were also observed only on the left eye (Figure 1, c, d). No lesions were observed on the skin or on any other mucosae. A skin biopsy from the patient's oral mucosa showed lymphocytic infiltration in the superficial dermis without apparent subepithelial blister. Direct immunofluorescence showed linear depositions of IgG, IgA, and C3 at the epithelial basement membrane zone (Figure 1, e-g). Circulating IgG and IgA autoantibodies were not detected by indirect immunofluorescence of normal human skin, while circulating IgA, but not IgG, autoantibodies were bound to the epidermal side of 1M NaCl-split normal human skin at 1:10 serum dilution (Figure 1, h, i). Commercially available IgG enzyme-linked immunosorbent assays (ELISAs) of BP180 NC16a domain, BP230, and type VII collagen (MBL, Nagoya, Japan) showed negative results. IgG and IgA immunoblotting analyses of six different antigen sources, including BP180 C-terminal domain recombinant protein, were all negative. However, ELISA of full-length BP180 was slightly positive for IgG antibodies (index = 5.79; cut-off <4.64). Immunoblotting analysis of full-length BP180 was negative for both IgG and IgA antibodies (Figure 1, j, k). Immunoblotting analysis of hemidesmosome-rich fraction was negative for both IgG and IgA antibodies to integrin ß4 (Figure 1, l). Based mainly on the clinical and immunological findings, we established a diagnosis of MMP with IgG and IgA autoantibodies, likely reactive with BP180. Because the patient refused systemic treatments, we prescribed a mouth rinse sodium gualenate hydrate and eyedrops of fluorometholone and purified sodium hyaluronate, which did not improve the oral and ocular mucosal symptoms during the 8 month follow-up period (Figure 1, m, n). Both IgG and IgA autoantibodies in anti-BP180-type MMP tend to react with the C-terminal domain of BP180 (2), and IgG autoantibodies in 39.7% of MMP patients reactive with the epidermal side of split skin were reported to be positive with BP180 C-terminal domain (3). The full-length BP180 ELISA shows excellent sensitivity for diagnosing BP180-type MMP (4). The different IgG and IgA reactivities among various methods used in the present study may be attributed either to different methodologies (i.e., immunoblotting or ELISA) or to the different substrates, since BP180-type MMP targets various regions of BP180, including the NC16a domain, the C-terminal domain, and the intracytoplasmic region (5). Precise diagnosis for MMP by various immunological methods is critical, because urgent and extensive treatments are necessary for the ocular and laryngeal lesions, which may result in loss of eyesight and airway obstruction, respectively. Acknowledgments: We express our gratitude to Ms. Mako Mine and Dr. Daisuke Hayashi, Department of Dermatology, Osaka City University Graduate School of Medicine in Osaka, Japan for the HD-rich fraction immunoblotting analysis, and Dr. Yoshiaki Hirako, Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan for the preparation of the HD-rich fraction sample. This work was supported by JSPS KAKENHI Grant Number JP20k08684 and the Hirosaki University Research Support System.

Interhospital transmission of vancomycin-resistant Enterococcus faecium in Aomori, Japan.

BACKGROUND: Spread of vancomycin-resistant Enterococcus (VRE) is a global concern as a significant cause of healthcare-associated infections. A series of VRE faecium (VREf) outbreaks caused by clonal propagation due to interhospital transmission occurred in six general hospitals in Aomori prefecture, Japan. METHODS: The number of patients with VREf was obtained from thirty seven hospitals participating in the local network of Aomori prefecture. Thirteen hospitals performed active screening tests for VRE. Whole genome sequencing analysis was performed. RESULTS: The total number of cases with VREf amounted to 500 in fourteen hospitals in Aomori from Jan 2018 to April 2021. It took more than three years for the frequency of detection of VRE to return to pre-outbreak levels. The duration and size of outbreaks differed between hospitals according to the countermeasures available at each hospital. Whole genome sequencing analysis indicated vanA-type VREf ST1421 for most samples from six hospitals. CONCLUSIONS: This was the first multi-jurisdictional outbreak of VREf sequence type 1421 in Japan. In addition to strict infection control measures, continuous monitoring of VRE detection in local medical regions and smooth and immediate communication among hospitals are required to prevent VREf outbreaks.

A Case of Possible Concurrence of Dermatitis Herpetiformis and Linear Immunoglobulin A / Immunoglobulin G Bullous Dermatosis.

Dear Editor, Linear immunoglobulin (Ig) A bullous dermatosis (LABD), one subtype of subepidermal autoimmune bullous skin diseases (AIBDs), is characterized by linear deposit of only IgA along the basement membrane zone (BMZ) on direct immunofluorescence (DIF) (1,2). Patients showing linear deposits of both IgA and IgG are diagnosed with linear IgA/IgG bullous dermatosis (LAGBD) (3,4). Dermatitis herpetiformis (DH) is another type of subepidermal AIBD characterized by clinically pruritic erythematous skin lesions with vesicles on the elbows, knees, and buttocks with granular IgA deposits of IgA by DIF (5). In this study, we report a Japanese case of a patient who showed possible concurrence of DH and LAGBD based on clinical, histological, and immunological findings. A 72-year-old Japanese man who had a past history of dyslipidemia and resected lung cancer but was not taking any medicines, presented with a one-year history of blistering skin lesions. Physical examination revealed erythemas and peripherally arranged vesicles and erosions on the bilateral elbows, knees, and the buttock (Figure 1, a-c). Mucous membranes were not involved. The results of all laboratory tests were within normal ranges, except for increased serum IgA level 351 mg/dL (normal ranges; 46-260 mg/dL). Skin biopsy histopathologically showed subepidermal blisters infiltrated with neutrophils and eosinophils (Figure 1, d). DIF showed deposits of IgG, IgA, and complement component 3 along the BMZ mainly in granular but partially in a linear pattern (Figure 1, e-g). Circulating IgG (Figure 1, h) and IgA (Figure 1, i) autoantibodies were not detected by indirect immunofluorescence (IIF) of normal skin, however, circulating IgA (Figure 1, j) but not IgG (Figure 1, k) antibodies were bound to both the epidermal and dermal sides by IIF of 1M NaCl-split normal skin. Commercially available enzyme-linked immunosorbent assays (ELISAs) for BP180 NC16a domain, BP230, and type Vll collagen (MBL, Nagoya, Japan), showed negative results for both IgG and IgA antibodies. IgG in-house ELISA for full length BP180 was also negative. IgG and IgA immunoblotting analyses of different antigen sources, including normal human epidermal and dermal extracts, recombinant proteins of NC16a, and C-terminal domains of BP180 region, BP230, purified laminin 332, and concentrated culture supernatant of HaCaT cells for LAD-1, were all negative. IgA ELISAs of tissue- and epidermal-transglutaminases were negative (1.92 AU/mL and 20.98 AU/mL, respectively; normal range <22.0 AU/mL). The patient was successfully treated with only topical corticosteroids with occasional mild local relapses. Japanese DH is different from European DH in some respects, i.e., DH is very rare in Japan due to genetic/HLA difference, absence of celiac disease, and frequent fibrillar IgA deposition in DIF. Therefore, we believe that this case is interesting as a rare Japanese DH case with complicated conditions. The clinical and immunochemical characteristics in the present case were compatible for both DH and LAGBD. Clinical features of vesicles on erythemas on the knees and buttock suggested DH, while histopathological features were compatible with LAGBD but also with DH, DIF results suggested both LAGBD and DH, and the results of IIF of 1M NaCl-split skin suggested LAGBD. All biochemical studies for autoantigens were negative, which suggested DH. However, autoantigens are not clearly detected in many LAGBD cases, either. IgA anti-epidermal transglutaminase antibody, a DH marker, was negative, but the titer was relatively high but within normal range. Therefore, we considered that this case might have developed DH and LAGBD concurrently. However, there may be two other possibilities: [1] this case was DH and non-pathogenic circulating autoantibodies were secondary production, and [2] LAGBD cases may sometimes show granular-linear BMZ deposition of IgG and IgA. Future studies on similar cases are needed to clarify our speculations.

Serum 3-Hydroxybutyrate in Patients with Psychogenic Somatoform Symptoms May Be a Predictor of the Effectiveness of Sertraline and Venlafaxine.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are often used to treat outpatients with psychogenic somatoform symptoms but prove ineffective in some cases. The metabolite 3-hydroxybutyrate (3HB) is currently attracting attention as a marker of the severity of depression. We investigated whether serum 3HB levels in patients with psychogenic somatoform symptoms can predict the effectiveness of sertraline and venlafaxine. PATIENTS AND METHODS: Physical and psychiatric problems were assessed in 132 outpatients, and symptomatic response and serum 3HB concentrations were examined before and after treatment with sertraline (50 mg/day) or venlafaxine (75 mg/day). RESULTS: In 30.3% of patients with psychogenic symptoms, serum 3HB was above the upper limit of normal (<80 µmol/L). According to multiple logistic regression analysis, only episodes of suicidal ideation showed a significant positive association with elevated 3HB (odds ratio 10.2; 95% confidence interval (CI) 2.46-42.2). The sensitivity of 3HB for the effectiveness of sertraline or venlafaxine for psychosomatic symptoms was 44.6%, but specificity was 93.9%. Hierarchical multiple logistic regression analysis identified 3HB as a better predictor of the effectiveness of medication (odds ratio 10.0; 95% CI, 2.49-40.3) than episodes of suicidal ideation. CONCLUSION: The present findings suggest that high serum 3HB levels in patients with psychogenic somatoform symptoms may be associated with suicidal ideation and the effectiveness of sertraline and venlafaxine at low to intermediate doses. The 3HB level may be a good predictor of the effectiveness of medication. Examination of serum 3HB levels may lead to earlier and more appropriate administration of sertraline and venlafaxine.

Autoantibodies to BPAG1e Trigger Experimental Bullous Pemphigoid in Mice.

Bullous pemphigoid (BP) is an autoimmune blistering disease that targets the hemidesmosomal proteins BP180 and BP230/BPAG1e. Whereas the role of anti-BP180 antibodies has been extensively characterized, the pathogenicity of anti-BPAG1e antibodies remains unclear. The purpose of this study is to elucidate the role of antibodies to BPAG1e in the experimental bullous pemphigoid models. We generated Bpag1 conditional knockout mice, where the knockout of Bpag1 is restricted to keratin 5-expressing epithelial cells. Bpag1 conditional knockout mice were immunized with the C-terminal portion of BPAG1e, and the splenocytes were injected into Rag2-/- mice intravenously. The recipient mice presented with erosion on the feet and tails. Microscopic examination showed subepidermal blisters and a linear deposition of IgG at the dermal-epidermal junction. To assess the potential role of trauma on BP development, we inflicted surface wounds on the dorsum of the Rag2-/- recipient mice after adoptive transfer. The wounded Rag2-/- mice had increased morbidity and severity of BP-like symptoms. Moreover, the depletion of B cells from splenocytes abolished a subepidermal blistering phenotype in vivo. These findings demonstrate that antibodies to BPAG1e might play a pathogenic role in causing subepidermal blistering, and external factors, including trauma, might be a trigger for BP development.

Clinical relevance of procalcitonin values in bacteremia.

INTRODUCTION: The aim of this study was to investigate procalcitonin levels according to the causative pathogens of bacteremia. The relationships between the clinical outcomes and procalcitonin levels were also studied. METHODS: From among 452 patients, 507 cases of positive blood culture were included in the present study. Procalcitonin levels were studied according to the pathogen types. The prevalence of septic shock and the mortality rates were also studied in four groups stratified by the procalcitonin levels (groups 1, 2, 3, and 4 had procalcitonin levels of <0.5 ng/mL, 0.5 ≤ 2.0 ng/mL, 2.0 < 10 ng/mL, and ≥10 ng/mL, respectively). RESULTS: The procalcitonin levels were significantly higher in bacteremia cases with Gram-negative rods (19.50 ng/mL), such as Escherichia coli (32.5 ng/mL), than those with Gram-positive rods (8.45 ng/mL) or Gram-positive cocci (9.21 ng/mL) (p < 0.01). The 28-day mortality rates in groups 1, 2, 3, and 4 were 6.0%, 12.0%, 14.9%, and 19.8%, respectively. The procalcitonin levels of samples taken before or on the same day of blood cultures were significantly lower than those taken one day after blood cultures. Multiple logistic regression analysis showed that C-reactive protein and procalcitonin ≥10 ng/mL were independently associated with a higher risk of mortality within 28 days. CONCLUSIONS: The PCT levels were higher in cases of bacteremia caused by GNR than those caused by GPR or GPC. The 28-day mortality rate increased as the PCT levels increased. Clinical importance of early evaluations and appropriate interpretation of procalcitonin levels for bacteremia were indicated.

Impact of Geographical Variations on the Prevalence of Multidrug-Resistant Organisms in Japan.

Emergence and spread of multidrug-resistant organisms (MDRO) is an urgent social and public health problem. Here, we carried out an epidemiological survey to clarify the geographical characteristics and factors influencing the prevalence of MDRO. Data on the prevalence of MDRO in 47 prefectures in Japan were extracted from the Japanese Nosocomial Infection Surveillance, a nationwide database for infection control. Potential factors for MDRO were analyzed using data selected from the pharmacological, medical service, infection control, environmental, social, and food-related categories, based on the characteristics of each organism and the correlations between them and MDRO prevalence. Statistical data for potential factors were obtained from public domains. The use of antibiotics was found to be correlated with the prevalence of penicillin-resistant Streptococcus pneumoniae, 3rd-generation cephalosporin- and fluoroquinolone-resistant Escherichia coli, and methicillin-resistant Staphylococcus aureus. Negative correlation between the consumption of food such as kelp and fermented soybeans that facilitate the growth of lactic acid bacteria and the prevalence of 3rd-generation cephalosporin- and fluoroquinolone-resistant E. coli suggested an association between the intestinal microflora and MDRO colonization. In addition to the use of antibiotics, lifestyle, food culture, and social factors such as tobacco smoking, average atmospheric temperature, prevalence of three-generation households, ratio of elderly population, average duration of tourist stay, chicken and fermented soybean consumption, and the competency of healthcare services may also affect MDRO prevalence.

HIV Reactivation in Latently Infected Cells With Virological Synapse-Like Cell Contact.

HIV reactivation from latency is induced by cytokines but also by cell contact with other cells. To better understand this, J1.1 cells, a latent HIV-1-infected Jurkat derivative, were cocultured with its parental Jurkat. J1.1 cells became p17MA-positive and produced a high level of HIV p24CA antigen, only when they were cocultured with stimulated Jurkat with cell-to-cell contact. In contrast, very little p24CA was produced when they were cocultured without cell contact. Similar results were obtained when latent ACH-2 and its parental A3.01 cells were cocultured. Confocal microscopy revealed that not only HIV-1 p17MA and gp120Env but also LFA-1, CD81, CD59, and TCR CD3 accumulated at the cell contact site, suggesting formation of the virological synapse-like structure. LFA-1-ICAM-1 interaction was involved in the cell-to-cell contact. When J1.1 was cocultured with TCR-deficient Jurkat, the p17MA-positive rate was significantly lower, although the cell-to-cell contact was not impaired. Quantitative proteomics identified 54 membrane molecules, one of which was MHC class I, that accumulated at the cell contact site. Reactivation from latency was also influenced by the presence of stromal cells. Our study indicated that latent HIV-1 in J1.1/ACH-2 cells was efficiently reactivated by cell-to-cell contact with stimulated parental cells, accompanying the virological synapse-like structure.

Nondestructive Evaluations of Melanin-related Compounds in the Skin Using Electron Paramagnetic Resonance and Permeability Measurements.

Melanin-related compounds in paraffin-embedded tissue specimens of basal cell carcinoma (BCC), seborrheic keratosis (SK), malignant melanoma (MM), and nevus pigmentosus (NP) were nondestructively investigated using permeability measurements (light penetration into pigmented lesion), X-band (9.4 GHz) electron paramagnetic resonance (EPR), and EPR imaging (EPRI). The paramagnetic species in BCC, SK, MM, and NP specimens were analyzed using intensity, linewidth, spectral pattern, and X-band EPRI. The EPR spectra of BCC, SK, and NP showed a single line pattern. The EPR signal intensities of the BCC, SK, and NP samples corresponded to the permeability values that are directly related to pigment color tone, except for MM. The correlation coefficient between EPR and permeability was supported by the high degree of linear relation in the range. We further analyzed MM and speculated that MM contains an additional signal of the pheomelanin radical. In MM and NP samples, two-dimensional (2D) EPRI revealed paramagnetic species distribution and different magnitudes. The paramagnetic (radical) species are directly related to the pigmented lesion site. To conclude, spectroscopic analyses suggest that pheomelanin-related compounds may exist in malignant melanoma.

Impact on Antifungal Susceptibility Patterns of Previous vs. Revised Clinical and Laboratory Standards Institute Breakpoints for Candida Species Isolated from Candidemia: Experience of Two Tertiary Care Institutions in Japan.

BACKGROUND: Candidemia has a high mortality rate. Identifying prognostic factors of candidemia, based on each regional data, is essential for better management. The Clinical and Laboratory Standards Institute (CLSI) recently revised Candida species-specific breakpoints (R-BP) for antifungal agents. Few studies have investigated the detection performance of resistance in Candida species by comparing the R-BP and previous species non-specific CLSI breakpoint (P-BP) among patients with candidemia. The primary objective was to investigate the impact of the R-BP on the antifungal susceptibility patterns of Candida species, while the secondary objective was to identify the prognostic factors of candidemia. METHODS: A total of 193 Candida species isolated from 187 patients with candidemia between January 2007 and December 2016 were examined. Susceptibility based on CLSI M27-A3 was defined as the P-BP and based on species-specific CLSI M59 or M60 breakpoint was defined as the R-BP. Multivariate Cox's hazard analysis was performed to identify prognostic factors within 30 days of the diagnosis of candidemia. RESULTS: A significant difference was observed in the susceptibility rate to fluconazole (FLCZ) (P-BP; 93.0% vs. R-BP; 79.4%) and to voriconazole (VRCZ) (P-BP; 97.2% vs. R-BP; 91.0%). The susceptibilities of C. parapsilosis, C. glabrata, and C. tropicalis to azole antifungal agents were markedly lower with the R-BP. Based on the R-BP, anti-fungal therapy was regarded as inappropriate for approximately 10% of the patients. The 30-day mortality rate was 29.4%. In a multivariate Cox's hazard analysis, age, lung disease, C. albicans, and the absence of antifungal therapy were associated with a high mortality rate, whereas serum albumin, C. parapsilosis, surgical wards, the removal of central venous catheter (CVC), and follow-up blood culture tests to confirm the clearance of Candida species were associated with a lower mortality rate. CONCLUSIONS: Early initiation of antifungal therapy, removal of CVC, and follow-up blood culture tests are essential for improving the outcome. The R-BP efficiently detected non-susceptible strains to FLCZ and VRCZ, particularly in non-albicans Candida species. The present results support the importance of antifungal susceptibility tests and interpretations based on the R-BP among patients with candidemia.

X-band EPR Spectroscopic Investigation of Seborrheic Keratosis.

Seborrheic keratosis (SK) is a common, noncancerous growth on the skin. However, the paramagnetic species (radicals) in pigmented SK have not been investigated yet. X-band (9 GHz) electron paramagnetic resonance (EPR) and EPR imaging (EPRI) were used to nondestructively investigate paraffin-embedded SK. Paramagnetic species in SK specimens were analyzed using linewidth, spectral pattern, and X-band EPRI. The EPR spectra of the SK showed a single line pattern. The EPR results revealed that the peak-to-peak linewidths (ΔHpp) of paraffin-embedded SK samples were 0.58 ± 0.02 mT. The g-value was 2.004 for those samples using EPR standards. EPR signal intensities of the SK samples reasonably corresponded to those for permeability values that are directly related to pigment color tone. Moreover, the two-dimensional (2D) EPRI of the SK showed the distribution of paramagnetic species in the samples with different magnitudes for the first time. The distribution corresponds to the pigmented region. We established that the paramagnetic species was melanin radicals, based on the EPR results obtained in addition to in vivo oxidation of melanin pigments. The present results suggest that EPR and 2D EPRI techniques can be useful for the radical characterization and evaluation of various types of SK.