Comparison of Endoplasmic Reticulum Stress Messenger Ribonucleic Acid Expression Between Chronic Otitis Media With and Without Cholesteatoma.

BACKGROUND: We evaluated and compared the role of endoplasmic reticulum stress in chronic otitis media with cholesteatoma and chronic otitis media without cholesteatoma. METHODS: The messenger ribonucleic acid expression of endoplasmic reticulum stress was measured and compared between chronic otitis media with cholesteatoma and chronic otitis media without cholesteatoma according to the presence or absence of bacteria, type of hearing loss, ossicle destruction, and facial canal dehiscence. RESULTS: The expression of immunoglobulin heavy chain-binding protein messenger ribonucleic acid was higher in the chronic otitis media without cholesteatoma group than in the chronic otitis media with cholesteatoma group, and Protein kinase RNA (PKR)-like endoplasmic reticulum kinase and activating transcription factor 6 messenger ribonucleic acid expression were higher in the chronic otitis media with cholesteatoma group than in the chronic otitis media without cholesteatoma group. CONCLUSION: Endoplasmic reticulum stress messenger ribonucleic acids were expressed in both chronic otitis media with cholesteatoma and chronic otitis media without cholesteatoma. The levels of expression of endoplasmic reticulum stress messenger ribonucleic acids differed according to clinical features, suggesting that different endoplasmic reticulum stress pathways are involved in the pathophysiology of different types of chronic otitis media.

Bacteriology and trends of antimicrobial resistance of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus in otitis media: A retrospective data analysis.

OBJECTIVES: Otitis media (OM) has a high prevalence worldwide and the treatment is crucial because hearing loss in children can lead to growth disorders such as language development disorders. The aim of this study is to analyse the changes in bacterial strains and the trends of antibiotic susceptibility in otitis media with effusion (OME), chronic otitis media (COM) and cholesteatomatous otitis media (Chole OM). DESIGN: This retrospective study involved 2926 patients diagnosed with OME, COM, or Chole OM between January 2000 and December 2020. The clinical data were collected and analysed through chart review from May 2021 to July 2021. SETTING: Two tertiary medical centres. PARTICIPANTS: The 2926 OM patients. MAIN OUTCOMES AND MEASURES: An otorrhea sample was collected on the first day of their hospital visit. Middle ear fluid samples for bacterial culture and antibiotics susceptibility test were collected from patients during middle ear surgery, including ventilation tube insertion. In each type of OM, the distribution of bacterial strains in the 2000s and the 2010s was compared. In addition, changes in the detection rate of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) and trends in their antibiotic susceptibility over the last 10 years were analysed. RESULTS: The most frequently detected bacterial strains in OME, COM and Chole OM over the study period were coagulase-negative Staphylococcus (CNS) (29.6%), MRSA (24.1%), and PA (20.1%). Compared to the 2000s, the proportion of non-typable Haemophilus influenzae in OME and MRSA in COM increased in the 2010s (27.4%-31.6% and 1.5%-29.5%, respectively). In total three types of OM, although there was no significant trend of change in detection rates of MRSA, PA, and multidrug resistant-P. aeruginosa (MDR-PA) during the last 10 years, resistance to the Quinolone class of MRSA and PA tended to increase (P < .05). CONCLUSIONS: The composition of bacterial strains in each types of OM has changed over the past 20 years. Additionally, the antibiotic resistance of MRSA and PA has increased in the last decade. Therefore, when using empirical antibiotics in necessary situations, it is necessary to change to an appropriate antibiotic through a bacterial culture test and antimicrobial susceptibility test.

Molecular Genetic Etiology and Revisiting the Middle Ear Surgery Outcomes of Branchio-Oto-Renal Syndrome: Experience in a Tertiary Referral Center.

OBJECTIVES: To explore the phenotypes and genotypes of patients with branchio-oto-renal (BOR) and branchio-otic (BO) syndrome, and to analyze the middle ear surgery outcomes qualitatively and quantitatively, proposing a factor usefully prognostic of surgical outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Eighteen patients with BOR/BO syndrome in 12 unrelated Korean families. INTERVENTION: Middle ear surgery, including either stapes surgery or ossicular reconstruction. MAIN OUTCOME MEASURE: Clinical phenotypes, genotypes, and middle ear surgery outcomes. RESULTS: Eight probands (66.7%) were confirmed genetically; the condition segregated as a dominant or de novo trait. Six EYA1 heterozygous variants were identified by exome sequencing and multiplex ligation-dependent probe amplification. All variants were pathogenic or likely pathogenic based on the ACMG/AMP guidelines. Two novel EYA1 frameshift variants (p.His373Phefs*4 and p.Gln543Asnfs*90) truncating a highly conserved C-terminal Eya domain were identified, expanding the genotypic spectrum of EYA1 in BOR/BO syndrome. Remarkably, middle ear surgery was individualized to ensure optimal audiological outcomes and afforded significant audiological improvements, especially in BOR/BO patients without enlarged vestibular aqueducts (EVAs). A significant difference in air-bone gap closure after middle ear surgery was noted between the two groups even after adjusting for confounders: -20.5 dB in ears without EVAs (improvement) but 0.8 dB in ears with EVAs (no change or deterioration). Furthermore, the success rate was significantly associated with the absence of EVA. CONCLUSIONS: The results of this study were against the notion that middle ear surgery is always contraindicated in patients with BOR/BO syndrome, and an EVA could be a negative prognostic indicator of middle ear surgery in BOR/BO patients. This may aid to determine the strategy of audiological rehabilitation in patients with BOR/BO syndrome.

Effect of closing material on hearing rehabilitation in stapedectomy and stapedotomy: A finite element analysis.

Stapedotomy or stapedectomy operations are often performed to treat otosclerosis. During the operation, the space created by bone removal is usually filled with a closing material such as fat or fascia. In this study, the effect of the Young's modulus of the closing material on the hearing level was investigated through the 3D finite element model of a human head including auditory periphery. The Young's moduli of the closing material used to implement stapedotomy and stapedectomy conditions in the model were varied from 1 kPa to 24 MPa. The results showed that the hearing level improved when the closing material was more compliant after stapedotomy. Therefore, when the stapedotomy was performed using fat whose Young's modulus is lowest among the potential closing materials, the hearing level recovered the best among all simulated cases. On the other hand, in stapedectomy, the Young's modulus did not have the linear relationship between the hearing level and the compliance of the closing material. Hence, the Young's modulus causing the best hearing rehabilitation in stapedectomy was found not at the end of the investigated range of Young's modulus but somewhere in the middle of the given range.

Correlation of Neutrophil-to-Lymphocyte Ratio and the Dilation of the Basilar Artery with the Potential Role of Vascular Compromise in the Pathophysiology of Idiopathic Sudden Sensorineural Hearing Loss.

Idiopathic sudden sensorineural hearing loss (SSNHL) currently lacks a clear etiology, as well as an effective treatment. One of the most probable explanations for SSNHL is impairment of the cochlear blood flow. However, dissimilar to a fundoscopic examination, direct observation of cochlear blood vessels is not possible. To indirectly support an ischemic etiology of SSNHL, we investigated whether the degree of initial hearing loss is associated with two atherosclerotic risk factors: dilatation of the basilar artery (BA) and a chronic subclinical inflammatory status measured by the neutrophil-to-lymphocyte ratio (NLR). This retrospective study collected data from 105 consecutive patients diagnosed with idiopathic SSNHL. Then, the patients were divided into two groups according to their NLR as "abnormally high NLR (>3.53, n = 22)" and "NLR within the normal range (0.78−3.53, n = 83)". The BA diameter and severity of initial hearing loss were significantly correlated with each other in the abnormally high NLR group (p < 0.001). However, there was no significant correlation between initial hearing loss and the BA diameter in the normal NLR group (p = 0.299). Therefore, the NLR may serve as a marker for SSNHL of vascular etiology and a rationale for magnetic resonance imaging examinations based on the pathophysiology.

Relationship between toll-like receptor expression in the distal facial nerve and facial nerve recovery after injury.

OBJECTIVES: This study aimed to determine whether toll-like receptor expression patterns differ in the distal facial nerve during recovery after crushing and cutting injuries. METHODS: Adult male Sprague-Dawley rats underwent crushing or cutting injury of the unilateral facial nerve. Their whisker movement and blink reflex were examined. Western blotting was performed with the normal nerve on the left side and the damaged nerve on the right side, four days, 14 days, and 3 months after injury. RESULTS: The scores of whisker movements and blink reflex in the crushing group showed improvements, while the score of the cutting group was significantly lower at 14 days and 3 months (p < 0.05). Western blotting showed that TLRs 11 and 13 increased in the crushing group, and TLRs 1, 2, 3, 4, 5, 8, 10, 11, 12, and 13 increased in the cutting group after 14 days (p < 0.05). After 3 months, TLRs 10 and 11 increased in the crushing group, and TLRs 1, 4, 5, 8, 11, and 12 increased in the cutting group (p < 0.05). CONCLUSION: TLRs 1, 4, 5, 8, and 12 are related to nerve degeneration after facial nerve injury, and TLRs 10, 11, and 13 are related to recovery from facial palsy.

Prognostic Factors Associated with Recovery from Recurrent Idiopathic Sudden Sensorineural Hearing Loss: Retrospective Analysis and Systematic Review.

Although idiopathic sudden sensorineural hearing loss (ISSNHL) is uncommon, recurrent ISSNHL is even rarer. The knowledge about factors associated with patient recovery from recurrent episodes is needed to counsel and treat the patients. Medical records of patients admitted for high dose oral steroid therapy for recurrent ISSNHL between January 2009 and December 2021 were reviewed. Their demographic and clinical characteristics, co-morbid symptoms, and audiologic results were analyzed. The 38 patients admitted for treatment of recurrent ISSNHL included 14 men and 24 women. Recovery rates after the first and recurrent episodes of ISSNHL were 78.9% and 63.2%, respectively. Patients who recovered after recurrent episodes showed significantly higher rates of ear fullness symptoms and early treatment onset than those who did not recover (p < 0.05 each). Of the 30 patients who recovered after the first episode, those who had ear fullness symptoms (p < 0.05, odds ratio (OR) 0.1, 95% confidence interval (CI) 0.01−0.76) and who showed a lower initial hearing threshold (p < 0.05, OR 1.06, 95% CI 1.01−1.12) during the recurrent episode showed significantly better or similar recovery than after the first episode. Ear fullness symptoms and less initial hearing loss were associated with a more favorable prognosis after intial than after recurrent ISSNHL.

The Roles of NOD-like Receptors in Innate Immunity in Otitis Media.

Acute otitis media (AOM) can persist or lead to various complications in individuals in which the innate immune system is impaired. In this context, impaired expression of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR), an intracellular pathogen-recognition receptor (PRR), is involved in the etiology of OM in humans and animals, affecting its development, severity, chronicity, recurrence, and associated complications. To assess this relationship, we reviewed literature reports relating NLR expression patterns with the pathophysiology and clinical features of OM in the larger context of impaired innate immunity. We summarized the results of published studies on the expression of NLRs in animals and humans in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. NLRs were expressed mainly in association with bacterial infection in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. In addition, expression of NLRs was affected by the presence or absence of bacteria, fluid characteristics, disease recurrence, tissue type, and repeated surgery. Various factors of the innate immune system are involved in the pathogenesis of OM in the middle ear. NLRs are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. Impaired NLR expression induced the development, chronicity and recurrence of OM and exacerbated associated complications, indicating that NLRs have important roles in the pathogenesis of OM.

Hearing Aid Effects and Satisfaction in Patients with Tinnitus.

This study aimed to evaluate the effectiveness of and satisfaction with hearing aids as a treatment option for tinnitus with hearing loss. METHODS: This retrospective study used the tinnitus handicap inventory (THI), the satisfaction with amplification in daily life (SADL) questionnaire, and a medical chart review. A total of 116 patients treated between August 2018 and December 2020 were included. All patients with tinnitus and hearing loss underwent the same counseling sessions. Sixty patients chose to have hearing aids fitted (aided group), whereas 56 patients chose not to (non-aided group). Both the groups had similar audiometric configurations, durations of tinnitus, and ages. Structured interviews were performed, with various measures evaluated using the visual analog scale (VAS) and the THI questionnaire, before and six months after fitting the hearing aids. The SADL questionnaire was administered 6 months after fitting the hearing aids. RESULTS: The patients' THI scores reduced 6 months after the counseling, but the improvement in the THI scores was only significant in the group that received hearing aids. There were significant differences between the VAS scores of the two groups, and the changes in the VAS scores in the groups were statistically different. Subjective satisfaction with a hearing aid increased with improvements to tinnitus-related discomfort. CONCLUSION: The study's results indicated that patients with hearing loss and tinnitus can be treated with hearing aids and counseling.

Voice Outcome After Cold Knife Surgery According to the Characteristics of Vocal Fold Polyp.

PURPOSE: Voice change is one of the major symptoms in patients with vocal fold polyp. As a result, phonomicrosurgery is commonly required in these patients. Since voice outcomes after polyp treatment can be variable according to polyp characteristics, we aimed to investigate the predicting factors of postoperative voice improvements in terms of polyp characteristics in patients with vocal fold polyp who underwent cold knife surgery. MATERIALS AND METHODS: A total of 77 patients who were diagnosed with vocal fold polyp and underwent phonomicrosurgery with cold knife instruments. The polyp characteristics of color, size, shape, and location were evaluated at baseline. Acoustic and aerodynamic analyses, voice handicap index questionnaire and grade, roughness, breathiness, asthenia, strain scale were evaluated at baseline and 6 weeks after surgery. RESULTS: All values of postoperative voice parameters improved after cold knife surgery. (P < 0.05) In patient with an organized vocal fold polyp, less improvement in postoperative values of maximum phonation time were observed. (P < 0.05) Likewise, less improvement of voice handicap index questionnaire score and grade, roughness, breathiness, asthenia, strain scale after surgery was shown in organized vocal fold polyp. (P < 0.05) CONCLUSIONS: Among the various polyp characteristics, the organized polyp was significantly related to relatively less improvement of objective and subjective voice parameters after surgery. These polyp characteristics would help to predict postoperative voice improvement and plan for personalized treatment in patients with vocal fold polyp.

Association of Metabolic Syndrome with Sensorineural Hearing Loss.

The prevalence of sensorineural hearing loss has increased along with increases in life expectancy and exposure to noisy environments. Metabolic syndrome (MetS) is a cluster of co-occurring conditions that increase the risk of heart disease, stroke and type 2 diabetes, along with other conditions that affect the blood vessels. Components of MetS include insulin resistance, body weight, lipid concentration, blood pressure, and blood glucose concentration, as well as other features of insulin resistance such as microalbuminuria. MetS has become a major public health problem affecting 20-30% of the global population. This study utilized health examination to investigate whether metabolic syndrome was related to hearing loss. METHODS: A total of 94,223 people who underwent health check-ups, including hearing tests, from January 2010 to December 2020 were evaluated. Subjects were divided into two groups, with and without metabolic syndrome. In addition, Scopus, Embase, PubMed, and Cochrane libraries were systematically searched, using keywords such as "hearing loss" and "metabolic syndrome", for studies that evaluated the relationship between the two. RESULTS: Of the 94,223 subjects, 11,414 (12.1%) had metabolic syndrome and 82,809 did not. The mean ages of subjects in the two groups were 46.1 and 43.9 years, respectively. A comparison of hearing thresholds by age in subjects with and without metabolic syndrome showed that the average pure tone hearing thresholds were significantly higher in subjects with metabolic syndrome than in subjects without it in all age groups. (p < 0.001) Rates of hearing loss in subjects with 0, 1, 2, 3, 4, and 5 of the components of metabolic syndrome were 7.9%, 12.1%, 13.8%, 13.8%, 15.5% and 16.3%, respectively, indicating a significant association between the number of components of metabolic syndrome and the rate of hearing loss (p < 0.0001). The odds ratio of hearing loss was significantly higher in subjects with four components of metabolic syndrome: waist circumference, blood pressure, and triglyceride and fasting blood sugar concentrations (p < 0.0001). CONCLUSIONS: The number of components of the metabolic syndrome is positively correlated with the rate of sensorineural hearing loss.

Toll-Like Receptors: Expression and Roles in Otitis Media.

Otitis media is mainly caused by upper respiratory tract infection and eustachian tube dysfunction. If external upper respiratory tract infection is not detected early in the middle ear, or an appropriate immune response does not occur, otitis media can become a chronic state or complications may occur. Therefore, given the important role of Toll-like receptors (TLRs) in the early response to external antigens, we surveyed the role of TLRs in otitis media. To summarize the role of TLR in otitis media, we reviewed articles on the expression of TLRs in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. Many studies showed that TLRs 1-10 are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. TLR expression in the normal middle ear mucosa is absent or weak, but is increased in inflammatory fluid of AOM, effusion of OME, and granulation tissue and cholesteatoma of COM. In addition, TLRs show increased or decreased expression depending on the presence or absence of bacteria, recurrence of disease, tissue type, and repeated surgery. In conclusion, expression of TLRs is associated with otitis media. Inappropriate TLR expression, or delayed or absent induction, are associated with the occurrence, recurrence, chronicization, and complications of otitis media. Therefore, TLRs are very important in otitis media and closely related to its etiology.

Objective and Measurable Biomarkers in Chronic Subjective Tinnitus.

Tinnitus is associated with increased social costs and reduced quality of life through sleep disorders or psychological distress. The pathophysiology of chronic subjective tinnitus, which accounts for most tinnitus, has not been clearly elucidated. This is because chronic subjective tinnitus is difficult to evaluate objectively, and there are no objective markers that represent the diagnosis or therapeutic effect of tinnitus. Based on the results of studies on patients with chronic subjective tinnitus, objective and measurable biomarkers that help to identify the pathophysiology of tinnitus have been summarized. A total of 271 studies in PubMed, 303 in EMBASE, and 45 in Cochrane Library were found on biomarkers related to chronic subjective tinnitus published until April 2021. Duplicate articles, articles not written in English, review articles, case reports, and articles that did not match our topic were excluded. A total of 49 studies were included. Three specimens, including blood, saliva, and urine, and a total of 58 biomarkers were used as indicators for diagnosis, evaluation, prognosis, and therapeutic effectiveness of tinnitus. Biomarkers were classified into eight categories comprising metabolic, hemostatic, inflammatory, endocrine, immunological, neurologic, and oxidative parameters. Biomarkers can help in the diagnosis, measure the severity, predict prognosis, and treatment outcome of tinnitus.

Analysis of Chronic Tinnitus in Noise-Induced Hearing Loss and Presbycusis.

Introduction: The most frequent causes of tinnitus associated with hearing loss are noise-induced hearing loss and presbycusis. The mechanism of tinnitus is not yet clear, although several hypotheses have been suggested. Therefore, we aimed to analyze characteristics of chronic tinnitus between noise-induced hearing loss and presbycusis. Materials and Methods: This paper is a retrospective chart review and outpatient clinic-based study of 248 patients with chronic tinnitus from 2015 to 2020 with noise-induced or presbycusis. Pure tone audiometry (PTA), auditory brainstem response (ABR), distortion product otoacoustic emissions (DPOAE), transient evoked otoacoustic emissions (TEOAE), and tinnitograms were conducted. Results: PTA showed that hearing thresholds at all frequencies were higher in patients with noise-induced hearing loss than the presbycusis group. ABR tests showed that patients with presbycusis had longer wave I and III latencies (p < 0.05 each) than patients with noise-induced hearing loss. TEOAE tests showed lower values in patients with noise-induced hearing loss than presbycusis at 1.5, 2, 3, and 4 kHz (p < 0.05 each). DPOAE tests showed that response rates in both ears at 1.5, 2, and 3 kHz were significantly higher in patients with presbycusis than noise-induced hearing loss (p < 0.05 each). Discussion: This study showed that hearing thresholds were higher, the loudness of tinnitus was smaller, and the degree of damage to outer hair cells was lower in patients with presbycusis than with noise-induced hearing loss. Moreover, wave I and III latencies were more prolonged in patients with presbycusis despite their having lower hearing thresholds. These phenomena may reflect the effects of aging or degeneration of the central nervous system with age. Further studies are needed to evaluate the etiologies of tinnitus.

Expression of endoplasmic reticulum stress mRNAs in otitis media.

BACKGROUND: Endoplasmic reticulum (ER) stress is a cellular defense mechanism that occurs when ER function is impaired. OBJECTIVE: This study was designed to evaluate the expression of major mRNAs of ER stress in patients with otitis media with effusion (OME), chronic otitis media (COM), and COM with cholesteatoma (CholeOM). MATERIAL AND METHODS: Specimens were collected during surgery from patients with OME, COM, and CholeOM, and the levels of ER stress mRNAs measured by real-time polymerase chain reaction. Levels of ER stress mRNAs were compared in the three groups and correlated with clinical findings and pus culture results. RESULTS: The level of CHOP mRNA was higher, and the levels of sXBP1 and ATF6 mRNAs lower, in the OME than in the other two groups (p < .05 each). Evaluation of bacterial pus culture negative patients showed that the level of ATF6 mRNA was higher in the CholeOM than in the other two groups (p < .05), whereas evaluation of bacterial pus culture positive patients showed that the level of CHOP mRNA was higher in the OME than in the other groups (p < .05). CONCLUSIONS AND SIGNIFICANCE: ER stress may be involved in the pathophysiology of OM and the levels of ER stress mRNAs were expressed differently in each type of otitis media according to bacterial culture test results.

Expression of endoplasmic reticulum stress-related mRNA in otitis media with effusion.

OBJECTIVES: The endoplasmic reticulum (ER) is an intracellular organelle involved in the synthesis and secretion of proteins. The ER stress response, which protects cells from cytotoxic proteins such as unfolded proteins, is related to several diseases including inflammation. In this study, we investigated the effect of ER stress on the pathophysiology of otitis media with effusion (OME). METHODS: Thirty-nine pediatric patients who were diagnosed with OME and underwent ventilation tube insertion were enrolled in this study. Exudate from the middle ear cavity was collected through ventilation insertion, and ER stress gene expression was analyzed via real-time polymerase chain reactions(PCR). RESULTS: There were no significant differences in ER stress-related mRNA expression between effusion culture-positive and culture-negative groups (p > 0.05). Expression of the C/EBP-homologous protein (CHOP) was higher in the otitis-prone group than in the non-otitis-prone group (p < 0.05). The most common type of fluid was mucoid, and inositol-requiring enzyme 1α expression was higher in serous fluid than in mucoid, mucopurulent, or purulent fluid (p < 0.05). CONCLUSIONS: Endoplasmic reticulum stress-related responses are activated in pediatric OME patients, and specific ER-stress related pathways are related to both the characteristics of fluid and the frequency of OME. Thus, ER stress-related responses affect the pathophysiology of OME in pediatric OME patients.

Cutoff value of serum procalcitonin as a diagnostic biomarker of infection in end-stage renal disease patients.

BACKGROUND/AIMS: Serum procalcitonin (PCT) levels are low in healthy individuals but are elevated in patients with a serious bacterial infection or sepsis. In this study, we examined the ability of serum PCT concentration to diagnose infections in end-stage renal disease (ESRD) patients, and sought to determine an appropriate threshold level. METHODS: Serum PCT levels were measured in ESRD patients on antibiotic therapy for a suspected bacterial infection (ESRD infection [iESRD] group, n = 21), and compared with those of ESRD patients on hemodialysis with no sign of infection (ESRD control [cESRD] group, n = 20). RESULTS: The mean serum PCT concentration of the iESRD group was significantly higher than in the cESRD group (2.95 ± 3.67 ng/mL vs. 0.50 ± 0.49 ng/mL, p = 0.006), but serum PCT concentrations did not correlate with severity of infection. The optimized threshold level derived for serum PCT was 0.75 ng/mL, rather than the currently used 0.5 ng/mL; this threshold demonstrated a sensitivity and specificity of 76.2% and 80.0% for infection and 100% and 60.6% for systemic inflammatory response syndrome, respectively, compared with the cutoff of 0.5 ng/mL. CONCLUSIONS: This study suggests that serum PCT at a cutoff value of 0.75 ng/mL is an appropriate indicator of infection in ESRD patients.

The effect of intravenous ascorbic acid in hemodialysis patients with normoferritinemic anemia.

BACKGROUND: Hemodialysis (HD) patients with functional iron deficiency often develop resistance to recombinant human erythropoietin (rhEPO). Recent studies have shown that intravenous ascorbic acid (IVAA) administration could override rhEPO resistance in HD patients. This study was undertaken to test the effects of IVAA in HD patients with normoferritinemic functional iron deficiency accompanied by EPO-hyporesponsive anemia. METHODS: Fifty-eight HD patients with normoferritinemic anemia (between 100 and 500 µg/L) were included and divided into the control (N=25) and IVAA (N=33) groups. IVAA patients received 500 mg of IVAA with each dialysis session for 3 months and an additional 4-month follow-up after the end of the therapy. RESULTS: Twenty patients had a response to IVAA with a significant increase in hemoglobin level (Hgb>1.0 g/dL) and reduction of weekly rhEPO dosage compared with the control group after 3 months of treatment (P<0.05). Compared with non-responders, transferrin saturation (TSAT) was significantly decreased in the responders group (26±11 vs. 35±14%, P<0.05) on baseline data. There was a significant increase in serum iron and TSAT (baseline vs. 3 months, serum iron 57±22 vs. 108±22 µg/dL, TSAT 26±11 vs. 52±7%, P<0.05) and a decrease in serum ferritin (377±146 vs. 233±145 ng/mL, P<0.05) in the responders group (N=20), but no significant changes in the control and non-responders groups (N=13) at 3-month treatment. CONCLUSION: IVAA can be a potent and effective adjuvant therapy for HD patients with rhEPO-resistant normoferritinemic anemia. In addition, IVAA can reduce the dosage of rhEPO for anemia correction.

Acute renal failure due to acute tubular necrosis caused by direct invasion of Orientia tsutsugamushi.

We describe a scrub typhus patient with acute renal failure for whom a diagnosis was made based on serology as well as immunohistochemical (IHC) staining and an electron microscopic examination (EM) of a renal biopsy specimen. For our case, we demonstrated by IHC staining and EM that renal failure was caused by acute tubular necrosis due to a direct invasion of Orientia tsutsugamushi.