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Abstract Associations between migraine and retinal vascular occlusion have been reported, but there is no large-scale and comprehensive study. Therefore, we aimed to determine risks of retinal vascular occlusion in patients with migraine. Using the Taiwan National Health Insurance Research Database from 2009 to 2020, we enrolled 628,760 patients with migraine and 628,760 matched individuals without migraine. Study outcomes were diagnoses of retinal vascular occlusion, including retinal artery occlusion (RAO) and retinal vein occlusion (RVO). Adjusted hazard ratio (aHR) of retinal vascular occlusion related to migraine was estimated. The cumulative incidences of subsequent retinal vascular occlusion, RAO, and RVO were significantly higher in migraine patients compared with controls (0.31% vs. 0.21%; 0.09% vs. 0.05%; 0.22% vs. 0.17%; all p

Abstract Background Previous studies have implicated inherited mutations in mitochondrial DNA (mtDNA) in sensorineural hearing loss (SNHL). However, the definitive association between mitochondrial 12S rRNA (MT-RNR1) variants and hearing loss in the population has not been well established, particularly in Asia. The objective of this retrospective cohort study was to assess the association between MT-RNR1 variants and the risk of SNHL in patients in Taiwan. Methods The cohort included 306,068 participants from Taiwan between January 2003 and December 2020. Participants were classified based on genetic variants, particularly mitochondrial mutations (rs267606618, rs267606619, rs267606617). MT-RNR1 variant cases were matched 1:10 with non-mutant patients by age, gender, and visit year, excluding those with pre-existing hearing loss. The primary endpoint was SNHL, identified using specific ICD-TM codes with a 90% positive predictive value. Medication exposure history was determined via self-report or electronic medical records in the hospital. Cox proportional hazard regression models were used to assess the association between MT-RNR1 variants and hearing loss, adjusting for various covariates. Kaplan-Meier survival curves and log-rank tests compared hearing loss incidence between groups. Results The mean age of the mtDNA variants group is 32.4 years, with a standard deviation of 19.2 years. The incidence density of hearing loss for the mutation group was 36.42 per 10,000 person-years (95% Confidence Interval [CI], 27.21–47.73), which was higher than the 23.77per 10,000 person-years (95% CI, 21.32–26.42) in the wild-type group (p = 0.0036). Additionally, diabetes mellitus was associated with an increased risk of developing SNHL in individuals with MT-RNR1 variants (adjusted hazard ratio = 1.76 [95% CI, 1.00-3.09], p

IntroductionIn medical education, the clerkship phase is a demanding period during which medical students learn to navigate the responsibilities of medical school and clinical medicine. Grit, a personal quality regarded as a non-cognitive trait, refers to perseverance and passion; specifically, it represents the ability to endure hardship and work industriously toward a goal. Most studies analysed grit as a single concept and few studies have investigated the effect of grit on the well-being of medical students through the whole-specialty training (i.e. surgical and non-surgical specialty rotations) required in clinical clerkships. Therefore, this study investigated whether associations exist between medical students’ grit, measured by the two subconstructs of perseverance and passion, and their well-being during clerkships in surgical and non-surgical specialty units.MethodsThis one-year prospective web-based questionnaire study enrolled fifth-year medical students at a tertiary medical centre in central Taiwan between September 2017 and July 2018 in their first-year clerkship. The students’ sex, age, and grit were measured at the start of their clerkship. Routine surveys were conducted over one year to assess burnout and compassion satisfaction for students’ well-being, and the training specialty characteristics of the surgical and non-surgical specialty departments were recorded. This study included 92 medical students and 1,055 survey responses from individual specialty rotations. Descriptive, univariate and multivariate analyses were performed.ResultsOur results revealed that medical students’ perseverance, as part of grit, was related to lower burnout and higher compassion satisfaction during clerkships, but not the subconstruct of passion. Moreover, the positive trait of perseverance measured in our study had greater explanatory power for compassion satisfaction than for burnout. Furthermore, the results revealed that older medical students suffered from less burnout than their younger counterparts, and that male medical students expressed higher compassion satisfaction than their female counterparts.DiscussionPerseverance, as a subconstruct of grit, is a positive personal quality for medical students’ clerkships, and methods driving the cultivation of perseverance in medical education should be considered. In addition, even though positive traits such as perseverance equipped medical students for compassion satisfaction, additional factors attributed to medical students’ burnout must be identified.

Abstract Background The prevalence of eosinophilic chronic rhinosinusitis (ECRS) has increased in Taiwan with a higher recurrence rate of nasal polyps after surgery. Therefore, we aimed to formulate the pre‐operative diagnostic criteria for patients with ECRS in Taiwan. Methods This case–control study included patients diagnosed with CRS with nasal polyps (CRSwNP) who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into ECRS and non‐eosinophilic CRS (NECRS) groups based on their histopathology. Demographic data, symptom severity scores, and computed tomography findings of the two groups were analyzed. We utilized receiver operating characteristic curve (ROC) analysis to evaluate parameters that could predict the diagnosis of ECRS. Results Total 408 CRSwNP patients were enrolled (ECRS group: 163; NECRS group: 245). ECRS group was strongly associated with asthma (6.1% vs. 2.0%, p = .03), higher blood eosinophil counts (4.3% vs. 2.7%, p 45, 2 points), serum eosinophil count percentage (>4%, 4 points), asthma (4 points), total serum IgE (>140 IU/mL, 4 points), Lund–Mackay score (>9.5, 4 points), and ethmoid‐to‐maxillary opacification ratio on CT (>1.5, 5 points). The cutoff score was 14 points (sensitivity, 70.2%; specificity, 93.3%). Conclusions Clinical‐feature‐based criteria may predict the diagnosis of ECRS before FESS in Taiwan. Level of Evidence Level 3.

Abstract Objective The objective of this research is to compare primary and salvage intratympanic (IT) steroid treatments in terms of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods The patients were randomized into two (primary and salvage) groups. Both groups received systemic steroid treatment for 2 weeks. The primary group also received IT dexamethasone injection three times during the treatment period, whereas the salvage group received IT dexamethasone injection only if no or slight recovery was noted at the 2‐week follow‐up. If needed, salvage steroid injection was administered three times during the following 2 weeks. Hearing recovery was analyzed according to the modified American Academy of Otolaryngology‐Head and Neck Surgery criteria. Results The degrees of hearing improvement at the 3‐month follow‐up were similar in the two groups. Compared with baseline, the pure‐tone average values and speech discrimination scores improved by 38.45 ± 21.95 dB HL and 34.32% ± 30.55%, respectively, in the primary group and 36.80 ± 22.33 dB HL and 31.87% ± 27.88%, respectively, in the salvage group (p = .762 and .659, respectively). In addition, the complete or partial hearing recovery rates were also similar in the primary and salvage groups (67.7% vs. 73.3%, respectively; p = .780). In the salvage group, 18 patients required no IT steroid injection because they recovered after systemic steroid treatment. Conclusion Primary and salvage IT steroid treatments for ISSNHL led to similar outcomes. In summary, salvage IT steroid injection is recommended for patients with ISSNHL patients to prevent unnecessary IT injection. Level of evidence 2.

Background: Various diseases involving the cavernous sinus can cause a condition called cavernous sinus syndrome (CSS), which is characterized by ophthalmoplegia or sensory deficits over the face resulting from the compression effect of internal structure. While tumor compression is the most reported cause of CSS, statistical data on CSS caused by infections are limited. Its risk factors, treatment methods, and clinical outcomes are not well-documented. Methods: In this retrospective study, we reviewed the data of patients admitted to a tertiary medical center from 2015 to 2022 with a diagnosis of acute and chronic sinusitis and at least one diagnostic code for CSS symptoms. We manually reviewed whether patients were involved in two or more of the following cranial nerves (CN): CN III, CN IV, CN V, or CN VI, or at least one of these nerves with a neuroimaging-confirmed lesion in the cavernous sinus. Results: Nine patients were diagnosed with rhinosinusitis-related CSS. The most common comorbidity was type 2 diabetes, and the most common clinical manifestations were diplopia and blurred vision. The sphenoid sinus was the most affected sinus. One patient expired due to a severe brain abscess infection without surgery. The remaining patients underwent functional endoscopic sinus surgery, and 50% of the pathology reports indicated fungal infections. Staphylococcus spp. was the most cultured bacteria, and Amoxycillin/Clavulanate was the most used antibiotic. Only four patients had total recovery during the follow-up one year later. Conclusions: CSS is a rare but serious complication of rhinosinusitis. Patients with diabetes and the elderly may be at a higher risk for this complication. Even after treatment, some patients may still have neurological symptoms.

Otomastoiditis caused by mycobacterial infections is uncommon and recalcitrant. Its clinical presentations, sometimes similar to those of common chronic suppurative otitis media, make diagnosis difficult. This retrospective study analyzed the clinical features, treatment course, and therapeutic outcomes of patients with mycobacterial otomastoiditis. The cases of six patients diagnosed with mycobacterial otomastoiditis or suspected mycobacterial infection between January 2007 and January 2019 in a single tertiary medical center in Taiwan were investigated. Information about predisposing factors, clinical features, culture reports, histopathology, treatment course, and outcomes were collected and analyzed. Relevant literature available in English was also reviewed. One patient was infected with tuberculous mycobacteria, two with suspected tuberculous mycobacteria, and three with nontuberculous mycobacteria. All six patients responded poorly to empiric antibiotic therapy, and diagnosis was not possible at their previous clinics. Five patients underwent tympanomastoidectomies; one was administered antimycobacterial medication without undergoing surgery. Mycobacterial infection was confirmed from a tissue culture or from the histopathology of the specimen, but in two patients, no definitive evidence of tuberculosis was found. Antimycobacterial medication was administered based on clinical suspicion, and improvement was noted. With appropriate therapy, all patients recovered, and no sequelae were observed after treatment. If empiric antibiotic therapy cannot achieve acceptable results, atypical infections, such as mycobacteria, should be considered. Antimycobacterial medication could be administered under clinical suspicion, serving as a diagnosis ex juvantibus. Surgical intervention might help reduce the bacterial load and obtain specimens for accurate diagnosis, but this may be unnecessary if appropriate antimycobacterial medication results in improvement. Early diagnosis and treatment can prevent complications in patients with recalcitrant otomastoiditis.

Abstract Background Service learning (SL) is an educational methodology presumed to help medical students be more empathetic and compassionate. We longitudinally investigated the level of empathy in medical students and how preclinical SL experience was related to their level of empathy in their clinical clerkships. Methods Our cohort comprised fifth-year medical students engaged in clerkships as part of a 7-year medical programme at one medical school in Taiwan. Surveys were conducted at the beginning of the clerkship in September 2015 (T1) to collect data on the medical students’ preclinical SL experience in curriculum-based service teams (CBSTs) and extracurricular service teams (ECSTs) and their SL self-efficacy, demographic characteristics, and empathy level. Subsequently, three follow-up surveys were conducted once every 3 months to determine the empathy level of the students during their clinical clerkships (T2–T4). Seventy students who returned the written informed consent and completed the baseline (T1) and two or more follow-up surveys (T2–T4) were included in our analysis with the response rate of 34%. In total, 247 responses across the 1-year clerkship were analysed. Descriptive statistics, paired t tests, and generalised estimating equations were employed. Results Our study revealed that changes in empathy level in the dimensions of perspective taking, compassionate care, and standing in patients’ shoes in their clinical clerkships. Relative to that at T1, their empathy decreased in perspective taking and compassionate care at T2–T4 but increased in standing in patients’ shoes at T3. Additionally, our study verified the positive effect of medical students’ preclinical SL experience in CBSTs and ECSTs on empathy in terms of compassionate care and perspective taking, respectively, but not on that of standing in patients’ shoes. Conclusions Separate investigations into subconstructs of empathy, such as perspective taking, compassionate care, and standing in patients’ shoes, in medical students may be necessary for exploring the various driving forces or barriers to developing empathy in medical students. Moreover, SL experience through both CBSTs and ECSTs at medical academies may have positive effects on medical students’ empathy in their clinical clerkships and should be promoted at medical schools.

Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

Abstract Neurofibromatosis type 2 (NF2) is a rare genetic disease involving multiple tumors of the central and peripheral nervous systems. Most patients with NF2 have bilateral vestibular schwannomas; nonvestibular schwannomas may also develop. While the majority of patients may present with hearing impairment, tinnitus, dizziness and balance disorders, some may present with cutaneous manifestations. We describe the case of a 20-year-old man who initially presented with a solitary subcutaneous painless nodule in the left preauricular area without any other symptoms. He received excisional biopsy for the preauricular mass and the pathologic diagnosis was schwannoma. Magnetic resonance imaging of brain and neck revealed multiple mass lesions over the bilateral cerebellopontine angle cisterns, extending to the bilateral internal auditory canals, bilateral cervical neuroforamens, cervical and upper thoracic spinal canals, and left posterior neck. The patient was diagnosed with NF2 according to the clinical criteria. He underwent gamma knife stereotactic radiosurgery for bilateral vestibular schwannomas and is now under regular monitoring. Conclusion NF2 patients may present with an isolated solitary cutaneous schwannoma with no other associated clinical findings. Further assessment is thus warranted in young patients presenting with a peripheral schwannoma despite absence of other clinical findings.

Abstract Background Resilience refers to the ability to be flexible and adaptive in response to challenges. Medical students in clerkship who are transitioning from medical studies to clinical practice face a variety of workplace demands that can lead to negative learning experiences and poor quality of life. This study explored whether medical students’ resilience plays a protective role against the stresses incurred during workplace training and on their professional quality of life during clerkships. Methods This was a 1-year prospective web-based questionnaire study comprising one cohort of medical students in their fifth year who were working as clerks as part of their 6-year medical education programme at one medical school in Taiwan between September 2017 and July 2018. Web-based, validated, structured, self-administered questionnaires were used to measure the students’ resilience at the beginning of the clerkship and their perceived training stress (i.e. physical and psychological demands) and professional quality of life (i.e. burnout and compassion satisfaction) at each specialty rotation. Ninety-three medical students who responded to our specialty rotation surveys at least three times in the clerkship were included and hierarchical regressions were performed. Results This study verified the negative effects of medical students’ perceived training stress on burnout and compassion satisfaction. However, although the buffering (protective) effects of resilience were observed for physical demands (one key risk factor related to medical students’ professional quality of life), this was not the case for psychological demands (another key risk factor). In addition, through the changes in R square (∆R2) values of the hierarchical regression building, our study found that medical students’ perceived training stresses played a critical role on explaining their burnout but their resilience on their compassion satisfaction. Conclusions Medical students’ resilience demonstrated a buffering effect on the negative relationship between physical demands and professional quality of life during clerkships. Moreover, different mechanisms (predictive paths) leading to medical students’ professional quality of life such as burnout and compassion satisfaction warrant additional studies.

BackgroundAn association between thyroid disease and tinnitus has been described previously but further longitudinal, population-based studies are limited.ObjectiveTo investigate the incidence of tinnitus in patients with hyperthyroidism in a national sample, and to identify risk level and associated factors for tinnitus in hyperthyroidism patients.DesignRetrospective cohort study. Patient data were collected from the Longitudinal Health Insurance Database (LHID 2000), which includes national claims data of patient expenditures for admissions or ambulatory care from 1996 to 2011.SettingTaiwan hospitals and clinics providing healthcare nationwide.ParticipantsPatients aged 20 years and older with newly diagnosed hyperthyroidism (ICD-9-CM code 242) between 2000-2010 were selected as the study cohort. Hyperthyroidism patient cohort were identified from the LHID2000. Those with tinnitus history (ICD-9-CM code 388.3) before the index date (first hyperthyroidism diagnosis), younger than 20 years, and with incomplete demographic data were excluded. The non-hyperthyroidism cohort included patients with no history of hyperthyroidism and no documented tinnitus.Main Outcomes and MeasuresIncidence of tinnitus was the primary outcome. Baseline demographic factors and comorbidities possibly associated with tinnitus, including age, sex, and comorbidities of hearing loss, vertigo, insomnia and anxiety, were retrieved from the LHID 2000. Patients were followed until end of 2011.ResultsDuring the study period, 780 (4.9%) hyperthyroidism patients and 2007 (3.2%) non-hyperthyroidism controls developed tinnitus. Incidence rate of tinnitus in the hyperthyroidism cohort was significantly higher in hyperthyroidism cohort (7.86 vs. 5.05 per 1000 person-years) than that in non-hyperthyroidism cohort. A higher proportion of patients with hyperthyroidism had comorbid insomnia (45.1% vs. 30.9%) and anxiety (14.0% vs. 5.73%) than those without hyperthyroidism. After adjusting for age, gender and comorbidities (vertigo, insomnia, anxiety, hearing loss), hyperthyroidism patients had 1.38-fold higher risk of tinnitus (95% CI = 1.27-1.50) than those without hyperthyroidism.ConclusionsThis large population-based study suggests patients with diagnosed hyperthyroidism was more prone to develop tinnitus. Our findings suggest evaluation for comorbid vertigo, insomnia, anxiety and/or hearing loss may identify patients who are at high risk of developing tinnitus in patients with hyperthyroidism.

Objectives This study investigated the long-term surgical outcomes of functional cholesteatoma surgery with canal wall reconstruction using autologous bone grafts as the primary material in patients with acquired cholesteatoma. Subjects and Methods Medical charts were retrospectively reviewed for all patients admitted to one institution for surgical intervention between 2010 and 2018. We analyzed 66 patients (66 ears) who underwent functional tympanomastoidectomy involving the use of autologous bone grafts for canal wall defect reconstruction. Surgical outcomes were evaluated by comparing preoperative audiometric results with follow-up data (at least 36 months after surgery). Logistic regression analyses were performed to determine prognostic factors related to long-term hearing success. These factors included classification and stage of cholesteatoma, stapes condition, ossicular chain damage, active infection of the middle ear, state of the contralateral ear, preoperative hearing thresholds, gender, and age. Results The mean follow-up period was 49.2 months. The recidivism rate was 6% (four of 66 ears). The pure-tone average significantly improved from 50.78 ± 19.98 to 40.81 ± 21.22 dB hearing level (HL; p

The main aim of this study is to compare the incidence rate and severity of deep neck infection (DNI) in patients post-UPPP+ T (uvulopalatopharyngoplasty plus tonsillectomy) and without UPPP+ T. We utilized the data derived from the Longitudinal Health Insurance Database (LHID) of the National Health Insurance Research Database (NHIRD) in Taiwan from 1 January 2000 to 31 December 2012. Patients who had undergone combined UPPP and tonsillectomy were selected using National Health Insurance (NHI) surgical order. Patients with DNI were selected using International Classification of Diseases (ICD-9-CM) code. A logistic regression model was applied for risk analysis. There were 1574 patients in the UPPP+ T cohort, and 6,296 patients who did not undergo combined UPPP and tonsillectomy for the control group. Our analysis showed that patients with an obstructive sleep apnea syndrome (OSAS) history constitute 76.1% (n = 1198) of the UPPP+ T cohort. Compared to the control group, there was no significantly increased incidence rate of DNI after UPPP+ T within 1–60 months. Patients undergoing combined UPPP and tonsillectomy had a lower intubation rate for DNI, with an adjusted odds ratio of 0.47 (95% CI = 0.32–0.69). The combined UPPP and tonsillectomy does not increase the risk of DNI within 1–60 months. Furthermore, combined UPPP and tonsillectomy can reduce the severity for DNI by decreasing the intubation rate and length of hospitalization.

Background: Air pollution is speculated to affect the reproductive health of women. However, a longitudinal association between exposure to air pollution and dysmenorrhea has not been identified, which this study aimed to examine this point.Methods: Two nationwide databases, namely the Taiwan Air Quality Monitoring database and the Taiwan National Health Research Institutes database were linked. Women with a history of dysmenorrhea (International Classification of Disease, Ninth Revision, Clinical Modification code 625.3) before 2000 were excluded. All participants were followed from January 1, 2000 until the diagnosis of dysmenorrhea, withdrawal from National Health Insurance, or December 31, 2013. Furthermore, air pollutants were categorized into quartiles with three cut-off points (25th, 50th, and 75th percentiles). The Cox regression model was used to calculate the hazard ratios of dysmenorrhea.Results: This study enrolled 296,078 women. The mean concentrations of yearly air pollutants were 28.2 (±12.6) ppb for nitric oxides (NOx), 8.91 (±7.93) ppb for nitric oxide (NO), 19.3 (±5.49) ppb for nitrogen dioxide (NO2), 0.54 (±0.18) ppm for carbon monoxide (CO), and 31.8 (±6.80) μg/m3 for PM2.5. In total, 12,514 individuals developed dysmenorrhea during the 12-year follow-up. Relative to women exposed to Q1 concentrations of NOx, women exposed to Q4 concentrations exhibited a significantly higher dysmenorrhea risk [adjusted hazard ratio (aHR)= 27.9, 95% confidence interval (CI) = 21.6–31.3]; similarly higher risk was found for exposure to NO (aHR = 16.7, 95% CI = 15.4–18.4) and NO2 (aHR = 33.1, 95% CI = 30.9–37.4). For CO, the relative dysmenorrhea risk in women with Q4 level exposure was 28.7 (95% CI = 25.4–33.6). For PM2.5, women at the Q4 exposure level were 27.6 times (95% CI = 23.1–29.1) more likely to develop dysmenorrhea than those at the Q1 exposure level.Conclusion: Our results showed that women would have higher dysmenorrhea incidences while exposure to high concentrations of NO, NO2, NOx, CO, and PM2.5.

Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcer, and gastrointestinal adenocarcinoma. Two major cytotoxins, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), interact closely with lipid rafts, contributing to H. pylori-associated disease progression. The Campylobacter jejuni cytolethal distending toxin consists of three subunits: CdtA, CdtB, and CdtC. Among them, CdtA and CdtC bind to membrane lipid rafts, which is crucial for CdtB entry into cells. In this study, we employed recombinant CdtC (rCdtC) to antagonize the functions of H. pylori cytotoxin in cells. Our results showed that rCdtC alleviates cell vacuolation induced by H. pylori VacA. Furthermore, rCdtC reduces H. pylori CagA translocation, which decreases nuclear factor kappa-B activation and interleukin-8 production, resulting in the mitigation of gastric epithelial cell inflammation. These results reveal that CdtC hijacks cholesterol to compete for H. pylori cytotoxin actions via lipid rafts, ameliorating H. pylori-induced pathogenesis.

Exposure to fine particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM2.5) is closely correlated with respiratory diseases. Microbiota plays a key role in maintaining body homeostasis including regulation of host immune status and metabolism. As reported recently, PM2.5 exposure causes microbiota dysbiosis and thus promotes disease progression. However, whether PM2.5 alters pulmonary microbiota distribution and aggravates bacteria-induced pathogenesis remains unknown. In this study, we used mouse experimental models of PM2.5 exposure combined with Streptococcus pneumonia infection. We characterized the airway microbiota of bronchoalveolar lavage fluid (BALF) by sequencing the 16S rRNA V3–V4 amplicon on the Illumina MiSeq platform, followed by a combination of bioinformatics and statistical analyses. Shannon-diversity index, observed ASVs, and Fisher’s diversity index indicated that microbiota richness was significantly decreased in the mice treated with either PM2.5 or pneumococcus when compared with the control group. The genera Streptococcus, Prevotella, Leptotrichia, and Granulicatella were remarkably increased in mice exposed to PM2.5 combined with pneumococcal infection as compared to mice with pneumococcal infection alone. Histopathological examination exhibited that a more pronounced inflammation was present in lungs of mice treated with PM2.5 and pneumococcus than that in mouse groups exposed to either PM2.5 or pneumococcal infection alone. Our results demonstrate that PM2.5 alters the microbiota composition, thereby enhancing susceptibility to pneumococcal infection and exacerbating lung pathogenesis.

Background: The evidence indicates that the optimal observation period following renal biopsy ranges between 6 and 8 h. This systematic review and meta-analysis explored whether differences exist in the complication rates of renal biopsies performed in outpatient and inpatient settings. Methods: We searched the MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 1985 to February 2020. Two reviewers independently selected studies evaluating the bleeding risk from renal biopsies performed in outpatient and inpatient settings and reviewed their full texts. The primary and secondary outcomes were risks of bleeding and major events (including mortality) following the procedure, respectively. Subgroup analysis was conducted according to the original study design (i.e., prospective or retrospective). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effect meta-analysis. Heterogeneity was assessed using the I2 test. Results: Data from all 10 eligible studies, which included a total of 1801 patients and 203 bleeding events, were included for analysis. Renal biopsies in outpatient settings were not associated with a higher bleeding risk than those in inpatient settings (OR = 0.81; 95% CI, 0.59–1.11; I2 = 0%). The risk of major events was also comparable across both groups (OR = 0.45; 95% CI, 0.16–1.29; I2 = 4%). Conclusions: Similar rates of bleeding and major events following renal biopsy in outpatient and inpatient settings were observed.

Hypopharyngeal squamous cell carcinoma (HSCC) is usually diagnosed at an advanced stage, leading to a poor prognosis. Even after improvement of surgical techniques, chemotherapy, and radiation technology, the survival rate of HSCC remains poor. Metformin, which is commonly used for type 2 diabetes mellitus (DM), has been suggested to reduce the risk of various cancer types. However, only a few clinical studies mentioned the relationship between metformin use and HSCC. Hence, the aim of this study was to elucidate the specific effect and mechanism of action of metformin in hypopharyngeal cancer. We first assessed whether metformin use has an effect on hypopharyngeal cancer patients with DM by conducting a retrospective cohort study. Our results showed that DM hypopharyngeal cancer patients who used metformin exhibited significantly better overall survival rates than that without metformin treatment. The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions. In addition, metformin activated the pathways of AMPKα and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells. These actions direct cells toward G1 cell cycle arrest, apoptosis, and autophagy. Our results, through combining a clinical cohort analysis with an in vitro study, demonstrate that metformin can be used for drug repositioning in the treatment of DM patients with hypopharyngeal cancer.

Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in NIHL and tinnitus, leading to potential new and innovative treatments. This review focuses on the assessment of NIHL, available treatments, and development of new pharmacologic and non-pharmacologic treatments based on recent studies of central auditory plasticity and adaptive changes in hearing. We discuss the mechanisms and maladaptive plasticity of NIHL, neuronal aspects of tinnitus triggers, and mechanisms such as tinnitus-associated neural changes at the cochlear nucleus underlying the generation of tinnitus after noise-induced deafferentation. We include observations from recent studies, including our own studies on associated risks and emerging treatments for tinnitus. Increasing knowledge of neural plasticity and adaptive changes in the central auditory system suggest that NIHL is preventable and transient abnormalities may be reversable, although ongoing research in assessment and early detection of hearing difficulties is still urgently needed. Since no treatment can yet reverse noise-related damage completely, preventative strategies and increased awareness of hearing health are essential.

Background: Direct evidence of lung cancer risk in Asian users of angiotensin-converting enzyme inhibitors (ACEIs) is lacking. Methods: The ACEI cohort comprised 22,384 patients aged ≥ 18 years with a first prescription of ACEI. The comparison angiotensin receptor blocker (ARB) cohort consisted of age-, sex- and comorbidity-matched patients at a ratio of 1:1. The primary outcome was the incidence of lung cancer, which was evaluated using a proportional hazard model. Results: The overall incidence rates of lung cancer in the ACEI and ARB cohorts were 16.6 and 12.2 per 10,000 person-years, respectively. The ACEI cohort had a significantly higher risk of lung cancer than the ARB cohort (adjusted hazard ratio [aHR]. = 1.36; 95% confidence interval [CI]. = 1.11−1.67). Duration−response and dose−response analyses revealed that compared with patients who did not receive ACEIs, patients who received ACEIs for more than 45 days per year (aHR = 1.87; 95% CI = 1.48−2.36) and patients who received more than 540 defined daily doses of ACEIs per year (aHR =1.80; 95% CI = 1.43−-2.27) had a significantly higher risk of lung cancer. The cumulative incidence of lung cancer was also significantly higher in the ACEI cohort than in the ARB cohort (log-rank test, p = 0.002). Conclusions: ACEI use is associated with an increased risk of lung cancer compared with ARB use. Patients using ARBs have a significantly lower risk of lung cancer than non-ARB users.

The increasing emergence of multidrug-resistant (MDR) bacteria has been recognized as a public health threat worldwide. Hospitalized patients and outpatients are commonly infected by non-fermenting Gram-negative bacilli (NFGNB), particularly the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB) and Pseudomonas aeruginosa. Antimicrobial agents are critical for treating the nosocomial infections caused by NFGNB. The aim of this study was to assess antimicrobial resistance and the use of antimicrobial agents. The bacterial isolates of 638,152 specimens from both inpatients and outpatients, retrieved from 2001 to 2008 at a medical center in central Taiwan, were examined for their susceptibility to various antimicrobial agents, including cefepime, imipenem, ciprofloxacin, gentamicin, amikacin, meropenem, and levofloxacin. Administrated prescriptions of the monitored antibiotics were analyzed using the Taiwan National Health Insurance Research Database (NHIRD). Our results show that the defined daily doses (DDDs) for cefepime, imipenem, and ciprofloxacin increased with time, and a trend toward reduced antimicrobial sensitivities of both ACB and P. aeruginosa was noticeable. In conclusion, the antimicrobial sensitivities of ACB and P. aeruginosa were reduced with the increased use of antibiotics. Continuous surveillance of antibiotic prescriptions and the prevalence of emerging resistance in nosocomial infections is warranted.

Introduction: Mentorship has been noted as critical to medical students adapting to clinical training in the medical workplace. A lack of infrastructure in a mentoring program might deter relationship building between mentors and mentees. This study assessed the effect of a redesigned clinical mentoring program from the perspective of clerks. The objective was to assess the benefits of the redesigned program and identify potential improvements. Methods: A redesigned clinical mentoring program was launched in a medical center according to previous theoretical and practical studies on clinical training workplaces, including the elements of mentor qualifications, positive and active enhancers for mentor–mentee relationship building, the timing of mentoring performance evaluation, and financial and professional incentives. A four-wave web survey was conducted, comprising one evaluation of the former mentoring program and three evaluations of the redesigned clinical mentoring program. Sixty-four fifth-year medical students in clerkships who responded to the first wave and to at least two of the three following waves were included in the study. A structured and validated questionnaire encompassing 15 items on mentor performance and the personal characteristics of the clerks was used. Mixed linear models were developed for repeated measurements and to adjust for personal characteristics. Results: The results revealed that the redesigned mentoring program improved the mentors’ performance over time for most evaluated items regarding professional development and personal support provided to the mentees. Conclusions: Our findings serve as an improved framework for the role of the institution and demonstrate how institutional policies, programs, and structures can shape a clinical mentoring program. We recommend the adoption of mentorship schemes for other cohorts of medical students and for different learning and training stages involved in becoming a physician.

Cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB) and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa). However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR). In this study, we further demonstrated that CDT suppresses the IR-induced autophagy pathway in PCa cells by attenuating c-Myc expression and therefore sensitizes PCa cells to radiation. We further showed that CDT prevents the formation of autophagosomes via decreased high-mobility group box 1 (HMGB1) expression and the inhibition of acidic vesicular organelle (AVO) formation, which are associated with enhanced radiosensitivity in PCa cells. The results of this study reveal the detailed mechanism of CDT for the treatment of radioresistant PCa.

To establish a real-time, web-based, customized audiometry database system, we worked in cooperation with the departments of medical records, information technology, and otorhinolaryngology at our hospital. This system includes an audiometry data entry system, retrieval and display system, patient information incorporation system, audiometry data transmission program, and audiometry data integration. Compared with commercial audiometry systems and traditional hand-drawn audiometry data, this web-based system saves time and money and is convenient for statistics research.

Clinically, we found the increased incidence of acquired colesteatoma in the patients with osteoporosis. In this study, we used a retrospective cohort to examine this association and to investigate the possible mechanism.We conducted a population-based retrospective cohort study by using the National Health Insurance Research Database (NHIRD). We identified an osteoporosis cohort comprising 37 124 patients newly diagnosed with osteoporosis aged 20 years or older. Patients in the comparison cohort had no history of osteoporosis and were frequency matched with the patients in the osteoporosis cohort according to sex, age, and index year.The acquired cholesteatoma incidence rates for the osteoporosis and comparison cohorts were 1.12 and 0.83 per 1000 person-years, respectively. After we adjusted for confounding factors, the osteoporosis cohort exhibited a 1.32-fold increased acquired cholesteatoma risk relative to the comparison cohort (hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 1.11-1.57). In addition, patients with no history of otitis media (HR = 1.33, 95% CI = 1.11-1.59), cancer (HR = 1.34, 95% CI = 1.12-1.60), or COPD (HR = 1.26, 95% CI = 1.05-1.52) in the osteoporosis cohort exhibited an increased risk of subsequent acquired cholesteatoma relative to those in the comparison cohort.Our cohort study indicated that patients with osteoporosis had a 1.31-fold increased acquired cholesteatoma risk relative to the comparison cohort. This risk was further increased in patients with comorbid otitis media. Hence, we recommend that otolaryngologists evaluate the condition of the middle ear of patients with osteoporosis.

Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is expressed in human nasopharyngeal and respiratory epithelium and has demonstrated antimicrobial activity. SPLUNC1 is now referred to as bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1). Reduced BPIFA1 expression is associated with bacterial colonization in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin 13 (IL-13), predominately secreted by T helper 2 (TH2) cells, has been found to contribute to airway allergies and suppress BPIFA1 expression in nasal epithelial cells. However, the molecular mechanism of IL-13 perturbation of bacterial infection and BPIFA1 expression in host airways remains unclear. In this study, we found that lipopolysaccharide (LPS)-induced BPIFA1 expression in nasal epithelial cells was mediated through the JNK/c-Jun signaling pathway and AP-1 activation. We further demonstrated that IL-13 downregulated the LPS-induced activation of phosphorylated JNK and c-Jun, followed by attenuation of BPIFA1 expression. Moreover, the immunohistochemical analysis showed that IL-13 prominently suppressed BPIFA1 expression in eosinophilic CRSwNP patients with bacterial infection. Taken together, these results suggest that IL-13 plays a critical role in attenuation of bacteria-induced BPIFA1 expression that may result in eosinophilic CRSwNP.

Background: Castleman disease and lymphoma each have a distinct treatment plan; however, they share the same features on contrast-enhanced computed tomography. Methods: To assess the quantitative outcomes of Castleman disease versus lymphoma using contrast-enhanced computed tomography based on Hounsfield units (HU). We retrospectively reviewed eight patients with unicentric Castleman disease and 30 patients with lymphoma based on pathological diagnosis at China Medical University Hospital between 2015 and 2020. Preoperative computed tomography with contrast scans was reviewed, and the HU of each tumor were measured. Results: This study included eight patients with unicentric Castleman disease (four men and four women; mean age, 33 years) and 25 patients with lymphoma (11 men and 14 women; mean age, 53 years). There was no significant difference in heterogeneity between the two diseases (0.161 ± 0.052 vs 0.239 ± 0.063, p = 0.22); however, enhancement in Castleman disease was higher than that in lymphoma (126.40 ± 31.90 vs 74.19 ± 7.11, p < 0.001), providing a very good diagnostic tool (cutoff point at 88.5-91.3, sensitivity 0.86/specificity 0.88). Furthermore, we found a highly linear relationship in Castleman disease, which was not noted in lymphoma. Conclusion: The value of HU provides a good diagnostic tool for the differential diagnosis of Castleman disease versus lymphoma in the neck lymph nodes. Considering the linear relationship in Castleman disease, an increasingly accurate differential diagnosis can be made. [ABSTRACT FROM AUTHOR]