Cortical volumetric changes after cochlear implantation in postlingually deaf adults: correlation with speech perception abilities.

This study aims to analyse the volumetric changes in brain MRI after cochlear implantation (CI), focusing on the speech perception in postlingually deaf adults. We conducted a prospective cohort study with 16 patients who had bilateral hearing loss and received unilateral CI. Based on the surgical side, patients were categorized into left and right CI groups. Volumetric T1-weighted brain MRI were obtained before and one year after the surgery. To overcome the artifact caused by the internal device in post-CI scan, image reconstruction method was newly devised and applied using the contralateral hemisphere of the pre-CI MRI data, to run FreeSurfer. We conducted within-subject template estimation for unbiased longitudinal image analysis, based on the linear mixed effect models. When analyzing the contralateral cerebral hemisphere before and after CI, a substantial increase in superior frontal gyrus and superior temporal gyrus (STG) volumes was observed in the left CI group. A positive correlation was observed in the STG and post-CI word recognition score in both groups. As far as we know, this is the first study attempting longitudinal brain volumetry based on post-CI MRI scans. We demonstrate that better auditory performance after CI is associated with structural restoration in central auditory structures.

Hearing impairment increases the risk of hip fracture-related mortality and recurrent hip fractures: A propensity score matching analysis.

PURPOSE: Despite the ongoing rise in hip fractures and the adverse effects of hearing impairment (HI) on increased mortality and morbidity, research addressing the influence of HI on mortality risk or complications in patients with hip fractures remains absent. This study aimed to analyze the effects of HI on mortality and treatment outcomes among patients with hip fracture. METHODS: We retrospectively collected data from consecutive patients diagnosed with hip fractures between January 2007 and March 2022 who had auditory examination records. From the initially enrolled 265 patients, data for 58 with HI and 58 without HI (control group) were extracted using a 1:1 propensity score matching. The primary outcome included comparison of mortality rates, and the secondary outcome encompassed the comparison of postoperative medical and surgical complications. RESULTS: The 1-year cumulative mortality rate was not significantly different between the HI and control groups, but the overall cumulative mortality rate was significantly higher in the HI than in the control group (63.0 % and 48.6, respectively; P = 0.046) in a follow-up period of up to 16 years. The HI group had a significantly higher incidence of "second hip fractures due to falls" than the control group (P = 0.016), although no differences in other medical and surgical complications were revealed. CONCLUSIONS: Awareness of the long-term risk of higher mortality when managing patients with hip fracture and HI is important. To reduce the risk of second hip fractures, paying more attention to fall prevention education and taking a more proactive approach, especially for those with HI.

Whole genome sequence and comparative genomic analysis of novel Rickettsia koreansis strain CNH17-7 isolated from human.

PURPOSE: To determine the genomic feature of novel spotted fever-causing Rickettsia koreansis strain CNH17-7, which is different from R. japonica that is a causative agent for Japanese spotted fever (JSF), and to perform its comparative genomic analysis. METHODS: Whole genome sequencing (WGS) was performed on R. koreansis strain CNH17-7 by using the Illumina Miseq system. After WGS, assembly and annotation were done by SPAdes. Then, its genomic features were compared with 19 different Rickettsia species. Based on the average nucleotide identity (ANI) value, an unweighted pair group method with an arithmetic mean (UPGMA) dendrogram was generated. Following the dendrogram analysis, pan-and core-genome analysis was performed. Then additional comparative analyses with two genetically closest Rickettsia species were conducted based on gene repertoire. RESULTS: R. koreansis strain CNH17-7 has a chromosome consisting of 1,392,633 bp with GC content of 32.4%. The ANI-derived UPGMA showed that R. koreansis strain CNH17-7 is genetically close to R. japonica YH and R. heilongjiangensis 054 but is distinctively differentiated. The ANI value of R. koreansis strain CNH17-7 to R. japonica YH and R. heilongjiangensis 054 are 98.14% and 98.04% respectively, indicating R. koreansis strain CNH17-7 is sufficient to be classified as a new species. Other than ANI, R. koreansis strain CNH17-7 also contains novel CDS and its COG functional category proportion which is distinct compared to R. japonica YH and R. heilongjiangensis 054. CONCLUSION: We have revealed genomic features of the novel R. koreansis strain CNH17-7. Hence, we propose R. koreansis strain CNH17-7 as new Rickettsia species.

Educational simulator for mastoidectomy considering mechanical properties using 3D printing and its usability evaluation.

Complex temporal bone anatomy complicates operations; thus, surgeons must engage in practice to mitigate risks, improving patient safety and outcomes. However, existing training methods often involve prohibitive costs and ethical problems. Therefore, we developed an educational mastoidectomy simulator, considering mechanical properties using 3D printing. The mastoidectomy simulator was modeled on computed tomography images of a patient undergoing a mastoidectomy. Infill was modeled for each anatomical part to provide a realistic drilling sensation. Bone and other anatomies appear in assorted colors to enhance the simulator's educational utility. The mechanical properties of the simulator were evaluated by measuring the screw insertion torque for infill specimens and cadaveric temporal bones and investigating its usability with a five-point Likert-scale questionnaire completed by five otolaryngologists. The maximum insertion torque values of the sigmoid sinus, tegmen, and semicircular canal were 1.08 ± 0.62, 0.44 ± 0.42, and 1.54 ± 0.43 N mm, displaying similar-strength infill specimens of 40%, 30%, and 50%. Otolaryngologists evaluated the quality and usability at 4.25 ± 0.81 and 4.53 ± 0.62. The mastoidectomy simulator could provide realistic bone drilling feedback for educational mastoidectomy training while reinforcing skills and comprehension of anatomical structures.

Do Patients with Benign Paroxysmal Positional Vertigo Have a Higher Prevalence of Osteoporosis? A Systematic Review and Meta-Analysis.

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder characterized by episodic vertigo. BPPV primarily affects older adults. Thus, understanding the potential relationship between BPPV and osteoporosis is clinically important. We performed a systematic search of MEDLINE (PubMed), Embase, and Cochrane Library databases for studies on the risk of osteoporosis between BPPV (+) and BPPV (-) groups up until 17 April 2023. We compared osteoporosis prevalence between groups and performed subgroup analyses for male, female, and older patients (aged ≥ 55 years). The 12 studies included 32,460 patients with BPPV and 476,304 controls. Pooled analysis showed that the BPPV (+) group had a significantly higher osteoporosis risk than the control group (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.45-2.06; p < 0.01). Subgroup analyses also presented similar trends as male (OR, 2.41; 95% CI, 1.18-4.90; p = 0.02), female (OR, 2.14; 95% CI, 1.57-2.92; p < 0.001), and older patient subgroups (OR, 1.91; 95% CI, 1.47-2.49; p < 0.01) showed a higher osteoporosis risk in the BPPV (+) group than in the control group. This meta-analysis supports the hypothesis that patients with BPPV have a higher osteoporosis prevalence than those without.

Long-Term Educational and Occupational Status of Prelingually Deaf Children Who Have Received a Cochlear Implant.

OBJECTIVE: To investigate the long-term educational and occupational status of prelingually bilateral deaf children who received a cochlear implant (CI) before the age of 7, and to identify factors that influence these outcomes. STUDY DESIGN: Retrospective chart review. SETTING: Single tertiary care center. METHODS: Seventy-one children who underwent CI surgery from 2000 to 2007 were included. The latest education and occupation status and word recognition score (WRS) were analyzed. RESULTS: The mean age at the time of surgery and the current age was 3.9 and 22.4 years. The age at CI showed a negative correlation with WRS. All subjects had graduated from high school or obtained an equivalent educational qualification. General high school graduates showed a higher WRS than those who attended a special education high school. The college entrance rate of CI patients (74.6% %) was comparable to that of the general population (72.5%). Subjects who went to college had a significantly better WRS than those who did not (51.4% vs 19.3%). Excluding 30 subjects currently enrolled in college, 26 (62%) of the remaining 41 were currently employed and engaged in various vocational activities, of which most (21 out of 26, 81%) were employed through vocational training institutes, or via special recruitment policy for the disabled. CONCLUSION: The long-term use of CI in prelingually deaf children enables not only speech perception but also produces comparable levels of education and employment to those of the general population. A good WRS and supportive policy were related to these successful outcomes.

Association Between Hearing Level and Mental Health and Quality of Life in Adults Aged >40 Years.

BACKGROUND AND OBJECTIVES: In this study, we investigated the effects of hearing loss on mental health and quality of life (QoL) using survey data in adults aged >40 years. Subjects and. METHODS: We obtained data from 10,921 individuals who responded to the fifth Korean National Health and Nutrition Examination Survey. Primary outcomes were measured using questionnaires that recorded stress perception, depressive mood, and suicidal ideation to evaluate mental health and motor ability, self-management, activities of daily living, pain or discomfort, and anxiety or depression to evaluate QoL. RESULTS: On multivariate analysis, suicidal ideation was more prevalent among older adults with hearing loss than in older adults without hearing loss. Motor ability was lower in individuals with hearing loss of >20 dB than in older adults with normal hearing. Categorization of the EuroQol-5 Dimension (EQ-5D) health state into upper and lower groups showed that the EQ-5D values were lower in the moderate-tosevere hearing loss group than in the mild hearing loss group. CONCLUSIONS: Among adults aged >40 years, those with hearing loss experienced more suicidal ideation, had lower motor ability, and lower overall QoL compared with these variables in older adults with normal hearing. Additionally, QoL scores were low in individuals with poor hearing.

The experience of device failure after cochlear implantation.

BACKGROUND: The present study describes the treatment of patients at a tertiary institution who experienced device failure after Cochlear Implantation (CI), as well as identifying prodromic symptoms that could assist in the timely identification and management of device failure. STUDY DESIGN: Retrospective database review (January 2000-May 2017). SETTING: Single tertiary hospital. METHODS: Factors recorded included the etiology of hearing loss; age at first and revision CI surgeries; surgical information, including operation time and approach; electrical outcomes after implantation; device implanted; symptoms of device failure; history of head trauma; and audiologic outcomes as determined by categories of auditory performance (CAP). RESULTS: From January 2000 to May 2017, 1431 CIs were performed, with 27 (1.9%) undergoing revision surgeries due to device failure. The most common etiology of hearing loss was idiopathic (12/27), followed by cochlear hypoplasia (5/27). Mean age at initial CI was 11.8 (1-72) years, with 21 being pre-lingual and 6 being post-lingual. Of the total devices initially implanted, 80.5% were from Cochlear, 15.9% from MED-EL, and 3.5% from Advanced Bionics. The failure rates of these devices were 1.3%, 3.1%, and 10.0%, respectively. The most suggestive symptom of device failure was intermittent loss of signal. Mean CAP scores were 5.17 before reimplantation and 5.54 and 5.81 at 1- and 3-years, respectively, after reimplantation. CONCLUSION: The most suggestive symptom preceding device failure was intermittent loss of signal. Patients who present with this symptom should undergo electrical examination for suspected device failure. Audiologic outcomes showed continuous development despite revision surgeries.

Risk Factors for Feeding Tube Dependency in Patients Undergoing Function Preservation Surgery for Advanced-Stage Laryngohypopharyngeal Cancer.

Dysphagia and feeding tube dependency commonly occur in patients with laryngeal or hypopharyngeal cancer (LHC) during and after treatment, often leading to poor functional outcomes. Therefore, we examined the factors related to feeding tube dependency among advanced-stage LHC patients undergoing curative surgery. This study included 69 consecutive patients who underwent conservative surgery for previously untreated, advanced-stage LHC (squamous cell carcinoma) between 2006 and 2016. Persistent feeding tube dependency was defined as 1 year or more after treatment completion. Binary logistic regression analysis was used to determine the factors associated with reactive prolonged and persistent feeding tube dependency. Cox proportional hazard regression analysis was used to determine the association between feeding tube dependency and survival. None of the study patients had a prophylactic feeding tube, but 15 (21.7%) patients had reactive feeding tube placement for 3 months or more. A total of 9 (13.0%) patients had persistent feeding tube dependency. Univariate analysis showed that age, tracheostomy, and common terminology criteria for adverse events (CTCAE) ≥ 3 were significantly associated with reactive prolonged and persistent feeding tube dependency (all P < 0.05). In the multivariate analysis, advanced age and CTCAE ≥ 3 remained the independent factors of reactive prolonged and persistent feeding tube dependency (all P < 0.05). Feeding tube dependency was not associated with overall survival or disease-free survival (P > 0.1). Feeding tube dependency might be related to clinical factors, such as age and severe adverse events, in the patients undergoing function-preserving surgery for advanced-stage LHC.

Molecular Typing on Human Blood Reveals the Borrelia afzelii Infection in Korea.

Lyme disease is a tick-borne infection in Korea. Here, clinical samples were collected from a 72-year old patient, with sudden onset of fever on April, 2018. The patient was passed away after 3rd day of doxycycline administration. The molecular diagnostic tests, nested polymerase chain reaction targeting 5S-23S rRNA intergenic spacer region (IGS) and multilocus sequence typing (MLST), showed positive for Borrelia afzelii from blood. Further, mutations in both 5S - 23S IGS and pepX allele of MLST were determined. Herein, we report the expected first death case by B. afzelii infection in Korea.

Automated multi-class classification for prediction of tympanic membrane changes with deep learning models.

BACKGROUNDS AND OBJECTIVE: Evaluating the tympanic membrane (TM) using an otoendoscope is the first and most important step in various clinical fields. Unfortunately, most lesions of TM have more than one diagnostic name. Therefore, we built a database of otoendoscopic images with multiple diseases and investigated the impact of concurrent diseases on the classification performance of deep learning networks. STUDY DESIGN: This retrospective study investigated the impact of concurrent diseases in the tympanic membrane on diagnostic performance using multi-class classification. A customized architecture of EfficientNet-B4 was introduced to predict the primary class (otitis media with effusion (OME), chronic otitis media (COM), and 'None' without OME and COM) and secondary classes (attic cholesteatoma, myringitis, otomycosis, and ventilating tube). RESULTS: Deep-learning classifications accurately predicted the primary class with dice similarity coefficient (DSC) of 95.19%, while misidentification between COM and OME rarely occurred. Among the secondary classes, the diagnosis of attic cholesteatoma and myringitis achieved a DSC of 88.37% and 88.28%, respectively. Although concurrent diseases hampered the prediction performance, there was only a 0.44% probability of inaccurately predicting two or more secondary classes (29/6,630). The inference time per image was 2.594 ms on average. CONCLUSION: Deep-learning classification can be used to support clinical decision-making by accurately and reproducibly predicting tympanic membrane changes in real time, even in the presence of multiple concurrent diseases.

Endoscopic Ear Surgery for Congenital Cholesteatoma in Children.

BACKGROUND: Endoscopic ear surgery is a promising technique for removing congenital cholesteatoma in children. It can provide greater visual access to hidden areas of the middle ear and facilitate middle-ear manipulation. This study compares a single-center experience in manag- ing congenital cholesteatoma with an endoscopic approach with that in managing congenital cholesteatoma with a conventional microscopic approach. METHODS: Records of consecutive patients aged under 8 with congenital cholesteatoma confined to the middle ear at our tertiary referral hospital from January 2013 to December 2018 were retrospectively reviewed. Operation time, hospital stay, postoperative complications, and recurrence/residue of congenital cholesteatoma were compared between patients receiving microscopic versus endoscopic surgery. RESULTS: A total of 33 pediatric patients aged from 19 months to 7 years were enrolled; 12 children underwent microscopic surgery, and 21 received an endoscopic approach for removing congenital cholesteatoma. The mean operative time was 1.61 hours for the microscopic group and 1.49 hours for the endoscopic group without statistical difference. No postoperative sensorineural hearing loss and complications were reported. Four cases of recurrence/residue were observed on the follow-up endoscopic exam or computed tomography, and no differences were shown between the 2 groups. Of the total patients, 94.7% (n=11) in the microscopic group and 90.5% (n=19) in the endoscopic group demonstrated an intact tympanic membrane without perforation or retraction after surgery. No audiological differences were reported between the 2 groups. CONCLUSION: Endoscopic ear surgery can effectively and safely remove congenital cholesteatoma in children and is not inferior to conventional microscopic approaches.

Long-term Changes of Hearing Thresholds and Eustachian Tube Function After Balloon Dilation of the Eustachian Tube in Patients With Chronic Otitis Media.

OBJECTIVES: This study aimed to evaluate long-term changes after balloon dilation of the Eustachian tube (BDET) in chronic otitis media (COM) patients with Eustachian tube (ET) dysfunction that persisted after tympanomastoidectomy (TM). METHODS: We retrospectively reviewed the medical records of consecutive patients who were diagnosed with COM and ET dysfunction and underwent TM at our tertiary hospital from 2016 to 2017. The tympanic membrane status, the presence of a ventilation tube, ability to perform the Valsalva maneuver, and audiologic changes after dilation of the ET were analyzed. RESULTS: This study included 20 patients (with 21 ears) who underwent TM but could not perform the Valsalva maneuver, showed a persistent air-bone gap, and eventually underwent BDET (male:female, 8:13; right:left, 11:10). Four ears showed perforation of the tympanic membrane after TM. Among the remaining 17 ears, 15 ears underwent ventilation tube insertion before BDET, while two ears underwent ventilation tube insertion and BDET simultaneously. Although none of the patients were capable of the Valsalva maneuver before BDET, 13 (62%) were able to perform the Valsalva maneuver successfully after BDET. When evaluating the tympanic membrane status at the latest follow-up, ventilation tubes were still present in eight ears. In the other 13 ears, intact tympanic membranes were present in nine out of 11 ears n the successful Valsalva group, whereas none of them were intact in the unsuccessful Valsalva group (P=0.014). The successful Valsalva group after BDET showed an improved air-bone gap of 8.9±12.4 dB, while the unsuccessful Valsalva group showed an aggravated air-bone gap of 3.8±11.8 dB at 1 year after BDET; this difference was statistically significant (P=0.031). CONCLUSION: The Valsalva maneuver could be performed successfully after BDET by 62% of patients with COM and ET dysfunction. BDET is helpful for successful hearing improvement and improved tympanic aeration in COM patients with ET dysfunction.

Successful management of severe allergic reactions to platelet transfusion with omalizumab: A case report.

RATIONALE: An allergic transfusion reaction is a common side effect of transfusions of red blood cells. Using washed red blood cells is the most effective method for preventing such a reaction. However, the availability of other washed transfusion components, including platelets, is limited. PATIENT CONCERNS: A 69-year-old patient with acute myeloid leukemia progressed from myelodysplastic syndrome and was treated with azacitidine. She experienced a minor reaction to platelet transfusion that initially responded to the administration of corticosteroids and antihistamines. However, she worsened even after subsequent preventive treatments and was referred to the emergency department due to anaphylaxis. The patient developed hypotension, chest pain, and dyspnea 10 minutes after the initiation of platelet transfusion. DIAGNOSES: She was diagnosed with platelet-induced anaphylaxis. INTERVENTIONS: In an attempt to prevent anaphylaxis, 150 mg of omalizumab was prescribed 1 week prior to transfusion. However, she experienced anaphylaxis again and was administered intramuscular epinephrine. For the following transfusion, we treated her with a 300 mg dose of omalizumab 24 hours before the transfusion. OUTCOMES: She tolerated well and continued to receive further chemotherapy and platelet transfusion with premedication. LESSONS: This case suggests that omalizumab is a good candidate for the management of severe allergic transfusion reactions.

Clinical usefulness of labyrinthine three-dimensional fluid-attenuated inversion recovery magnetic resonance images in idiopathic sudden sensorineural hearing loss.

PURPOSE OF REVIEW: Literature on the use of current magnetic resonance imaging (MRI) for patients with idiopathic sudden sensorineural hearing loss (ISSNHL) is reviewed, emphasizing the role of three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) MRI. The discussion focuses on the diagnostic role of temporal bone MRI using 3D-FLAIR and the relationship between MRI findings, clinical symptoms, and hearing outcome. RECENT FINDINGS: The currently suggested MRI protocol for SSNHL includes a 3D T2-weighted steady-state free procession sequence or its equivalent, pre and postcontrast T1-weighted, and pre and postcontrast 3D-FLAIR sequences. The 3D-FLAIR image identifies an underlying labyrinthine condition in 24-57% of patients with ISSNHL, contributing to understanding the pathophysiologic mechanisms (e.g., labyrinthitis or labyrinthine hemorrhage). Recent studies demonstrated consistent results that initial hearing loss could be related to the signal change on the 3D-FLAIR image. Various results on 3D-FLAIR image value prediction for the final hearing outcome were shown. SUMMARY: 3D-FLAIR MRI application identifies an underlying labyrinthine condition. Abnormal MRI findings correlate with initial hearing loss and accompanying symptoms and hearing outcome. Performing temporal bone MRI with 3D-FLAIR sequence may clarify probable ISSNHL pathophysiology, improve diagnostic accuracy, provide prognostic information to physicians, and possibly guide toward a more specific treatment.

Association between body weight variability and incidence of Parkinson disease: A nationwide, population-based cohort study.

BACKGROUND AND PURPOSE: Although body weight variability has been associated with mortality, cardiovascular disease, and dementia, the relationship between body weight variability and Parkinson disease (PD) has rarely been studied. We aimed to investigate the longitudinal association between body weight variability and PD incidence. METHODS: A nationwide population-based, cohort study was conducted using the database from the Health Insurance Review and Assessment Service of the whole Korean population. We analyzed 2,815,135 participants (≥40 years old, mean age = 51.7 ± 8.6 years, 66.8% men) without a previous PD diagnosis. We determined individual body weight variability from baseline weight and follow-up visits. We used Cox proportional hazards regression models. RESULTS: The highest quartile group was associated with increased PD incidence compared with the lowest quartile group after adjustment for confounding factors (hazard ratio [HR] = 1.18, 95% confidence interval [CI] = 1.08-1.29). In contrast, baseline body mass index, baseline waist circumference, and waist circumference variability were not associated with increased PD incidence. In the body weight loss group, individuals within the quartile of the highest variation in body weight showed a higher HR of PD risk than those within other quartiles (HR = 1.41, 95% CI = 1.18-1.68). CONCLUSIONS: Body weight variability, especially weight loss, was associated with higher PD incidence. This finding has important implications for clinicians and supports the need for preventative measures and surveillance for PD in individuals with fluctuating body weight.

Diagnostic Accuracies of Laryngeal Diseases Using a Convolutional Neural Network-Based Image Classification System.

OBJECTIVES/HYPOTHESIS: There may be an interobserver variation in the diagnosis of laryngeal disease based on laryngoscopic images according to clinical experience. Therefore, this study is aimed to perform computer-assisted diagnosis for common laryngeal diseases using deep learning-based disease classification models. STUDY DESIGN: Experimental study with retrospective data METHODS: A total of 4106 images (cysts, nodules, polyps, leukoplakia, papillomas, Reinke's edema, granulomas, palsies, and normal cases) were analyzed. After equal distribution of diseases into ninefolds, stratified eightfold cross-validation was performed for training, validation process and remaining onefold was used as a test dataset. A trained model was applied to test sets, and model performance was assessed for precision (positive predictive value), recall (sensitivity), accuracy, F1 score, precision-recall (PR) curve, and PR-area under the receiver operating characteristic curve (PR-AUC). Outcomes were compared to those of visual assessments by four trainees. RESULTS: The trained deep neural networks (DNNs) outperformed trainees' visual assessments in discriminating cysts, granulomas, nodules, normal cases, palsies, papillomas, and polyps according to the PR-AUC and F1 score. The lowest F1 score and PR-AUC of DNNs were estimated for Reinke's edema (0.720, 0.800) and nodules (0.730, 0.780) but were comparable to the mean of the two trainees' F1 score with the best performances (0.765 and 0.675, respectively). In discriminating papillomas, the F1 score was much higher for DNNs (0.870) than for trainees (0.685). Overall, DNNs outperformed all trainees (micro-average PR-AUC = 0.95; macro-average PR-AUC = 0.91). CONCLUSIONS: DNN technology could be applied to laryngoscopy to supplement clinical assessment of examiners by providing additional diagnostic clues and having a role as a reference of diagnosis. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2558-2566, 2021.

Association between cotinine-verified smoking status and moderately increased albuminuria in the middle-aged and older population in Korea: A nationwide population-based study.

OBJECTIVES: Although several self-reported questionnaire-based studies have found an association between smoking and moderately increased albuminuria, this result remains controversial. We investigated whether moderately increased albuminuria was associated with smoking status, verified by urinary cotinine (an objective biomarker of tobacco exposure), using population-based, nationally representative data. METHODS: This study included 2059 participants aged ≥ 50 years from the 2014 Korean National Health and Nutrition Examination Survey. Individuals with a urinary cotinine level ≥ 50 ng/mL were identified as cotinine-verified smokers. Moderately increased albuminuria was defined as a urine albumin-to-creatinine ratio ranging between ≥ 30 mg/g and < 300 mg/g. Multivariable logistic regression was used to evaluate the association between cotinine-verified smoking status and moderately increased albuminuria. RESULTS: Among the study participants, 16.9% were cotinine-verified smokers, 84.8% of whom were men. After adjustment for multiple covariates, cotinine-verified smokers showed a significant positive association with moderately increased albuminuria (adjusted odds ratio: 4.37, 95% confidence interval: 1.63-11.71) compared with cotinine-verified non-smokers. The association between urinary cotinine and moderately increased albuminuria did not differ with age, sex, obesity, or comorbidities (P-value for interaction > 0.05 in all cases). CONCLUSION: This large-scale observational study showed that cotinine-verified smoking is associated with moderately increased albuminuria in the Korean middle-aged and older general population, suggesting that smoking must be strictly controlled to reduce the risk of moderately increased albuminuria.

Tick-borne rickettsiae in Midwestern region of Republic of Korea.

To identify spotted fever group (SFG) rickettsiae among ticks collected by dragging at eight sites in three provinces of the midwestern region of the Republic of Korea (ROK), genus- and species-specific quantitative real-time PCR (qPCR) assays and sequencing were performed. DNA was extracted from a total of 2,312 ticks that were assayed individually (n=140) or in pools (n=444), resulting in a total of 584 individual and pooled tick samples. The 584 tick samples were screened with the genus-specific qPCR assay (Rick17b) and produced 265 (45.38%) positive reactions [individual (n=64) and pooled (n=101) samples]. Of these genus-specific positive samples, 57 (21.51%) were identified as Candidatus Rickettsia longicornii and 48 (18.11%) were identified as R. monacensis by species-specific qPCR assays. Subsequently, nested PCR (nPCR) was performed with 120 samples, which tested positive samples for genus-specific, but not species-specific, qPCR assays. The sequences of ompA and ompB genes showed how many close relatedness to Ca. R. longicornii and Ca. R. jingxinensis isolate Xian Hl-79, uncultured Rickettsia sp. Y27-1, Ca. R. tasmanensis strain T152, R. endosymbiont of H. longicornis tick 47, and R. koreansis strain CNH17-7. In conclusion, we successfully detected specific rickettsial agents using qPCR and a sequence-based analysis approach that demonstrated the prevalence of various tick-borne Rickettsia spp. in midwestern ROK.

T-cell agonists in cancer immunotherapy.

Cancer cells can evade immune surveillance in the body. However, immune checkpoint inhibitors can interrupt this evasion and enhance the antitumor activity of T cells. Other mechanisms for promoting antitumor T-cell function are the targeting of costimulatory molecules expressed on the surface of T cells, such as 4-1BB, OX40, inducible T-cell costimulator and glucocorticoid-induced tumor necrosis factor receptor. In addition, CD40 targets the modulation of the activation of antigen-presenting cells, which ultimately leads to T-cell activation. Agonists of these costimulatory molecules have demonstrated promising results in preclinical and early-phase trials and are now being tested in ongoing clinical trials. In addition, researchers are conducting trials of combinations of such immune modulators with checkpoint blockade, radiotherapy and cytotoxic chemotherapeutic drugs in patients with advanced tumors. This review gives a comprehensive picture of the current knowledge of T-cell agonists based on their use in recent and ongoing clinical trials.