Incidence and Characteristics of Intraocular Lens Dislocation in South Korea from 2002 to 2021: A Nationwide Population-based Study.

Purpose: This study aimed to analyze the incidence and characteristics of intraocular lens (IOL) dislocation after cataract surgery in South Korea. Methods: We retrospectively analyzed the incidence of IOL dislocation after cataract surgery in patients diagnosed between 2002 and 2021. Data of all pseudophakic patients who underwent secondary IOL or IOL exchange surgeries due to IOL dislocation were extracted from the Korean National Health Insurance System (KNHIS) database and the Korean Standard Classification of Diseases-7 codes. The incidence per 1,000,000 person-years and corresponding 95% confidence intervals (CIs) were calculated. Results: Between 2002 and 2021, 39,965 (0.82 %) of the 4,848,125 pseudophakic patients were diagnosed with IOL dislocation and surgically treated. The incidence of IOL dislocation requiring surgery in pseudophakic patients was 28,900/1,000,000 person-years (95% CI: 28,431-29,369), comprising 57,800 cases in male and 10,800 in female patients (95% CI: male: 56,730-58,870 vs. 95% CI: female patients: 10,523-11,077), and mean male-to-female ratio was 5.35. The incidence rate peaked in younger age group below 40 years, showing 107,000 per 1,000,000 person-years (95% CI: 102,900-111,100), and the average age of IOL dislocation requiring surgery was 68.1 ± 10.7 years. The average time lapse from cataract surgery to secondary IOL surgery due to IOL dislocation was 4.1±4.7 years (median, 2.2 years), and the number of secondary IOL surgery due to dislocation of artificial lens rapidly occurred 10 years after cataract surgery among all age groups. Conclusions: The incidence of IOL dislocation requiring surgery was higher in younger and male patients. Our findings could be expected to aid establishing future healthcare policies for South Korean populations with an increased risk of IOL dislocation after cataract surgery.

Genomic and single-cell characterization of patient-derived tumor organoid models of head and neck squamous cell carcinoma.

Head and Neck Squamous Cell Carcinoma (HNSCC) remains a significant health burden due to tumor heterogeneity and treatment resistance, emphasizing the need for improved biological understanding and tailored therapies. This study enrolled 31 HNSCC patients for the establishment of patient-derived tumor organoids (PDOs), which faithfully maintained genomic features and histopathological traits of primary tumors. Long-term culture preserved key characteristics, affirming PDOs as robust representative models. PDOs demonstrated predictive capability for cisplatin treatment responses, correlating ex vivo drug sensitivity with patient outcomes. Bulk and single-cell RNA sequencing unveiled molecular subtypes and intratumor heterogeneity (ITH) in PDOs, paralleling patient tumors. Notably, a hybrid epithelial-mesenchymal transition (hEMT)-like ITH program is associated with cisplatin resistance and poor patient survival. Functional analyses identified amphiregulin (AREG) as a potential regulator of the hybrid epithelial/mesenchymal state. Moreover, AREG contributes to cisplatin resistance via EGFR pathway activation, corroborated by clinical samples. In summary, HNSCC PDOs serve as reliable and versatile models, offer predictive insights into ITH programs and treatment responses, and uncover potential therapeutic targets for personalized medicine.

Epidemiologic relationship between alcohol flushing and smoking in the Korean population: the Korea National Health and Nutrition Examination Survey.

Although facial flushing after drinking alcohol (alcohol flushing response) is common in Asian populations, the epidemiological features in a large sample have been investigated in only a few studies. This study assessed the epidemiologic characteristics and associated factors for alcohol flushing in a Korean population. This study was based on data collected during the 2019 Korea National Health and Nutrition Examination Survey (KNHANES). A total of 5572 Korean adults was included in the general population group, and the alcohol flushing group consisted of 2257 participants. Smoking and physical activity were evaluated as possible associated factors for alcohol flushing. The overall prevalence of alcohol flushing was estimated at 40.56% of the general population (43.74% in males and 37.4% in females), and the prevalence was highest at 60-69 years of age and lowest in individuals older than 80 years. Occasional, frequent, and persistent alcohol flushing was reported by 11.9%, 3.7% and 15.0% of current flushers, among whom persistent flushers consumed the least amount of alcohol. Subjects who currently smoke had a higher propensity of alcohol flushing (adjusted OR 1.525, 95% CI 1.2-1.938), and subjects with smoking history of 20-29 pack-years (PYs) showed the highest association (adjusted OR 1.725, 95% CI 1.266-2.349) with alcohol flushing after adjustment for confounders. In contrast, significant association was not found between physical activity and alcohol flushing. The results demonstrated that current smoking status is shown to be significantly associated with alcohol flushing, and that current smokers with a history of smoking ≥ 20 PYs had a higher likelihood of alcohol flushing than non-smokers or ex-smokers.

A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma.

PURPOSE: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND METHODS: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses. RESULTS: Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T. CONCLUSIONS: Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.

Preventive effect of aripiprazole once-monthly on relapse into mood episodes in bipolar disorder: A multicenter, one-year, retrospective, mirror image study.

BACKGROUND: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment. METHODS: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit. RESULTS: The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM. LIMITATIONS: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times. CONCLUSION: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.

Estimation of the Three Phases by Direct Cost of Care for Non-surviving Patients with Cancer: A National Population-based Patient-level Study.

Background: Determining the cost structure of medical care from diagnosis to the death of patients with cancer is crucial for establishing budgets to support patients with cancer. The breakdown of the cost estimation in distinct phases of survival is essential for optimizing the allocation of limited funds. Therefore, this study aims to examine the patterns of direct medical costs of cancer care associated with seven major cancer types and estimate cost thresholds to distinguish each phase based on the incurred cost. Methods: In this nationwide, population-based study, we used claims data from the National Health Insurance Service, Korea. Patients newly diagnosed with cancer since 2006 and who died in 2016-2017 were enrolled, and their use of medical services during cancer survival from at least 6 months up to 12 years was observed. The monthly cost exhibited a non-linear function with two unknown thresholds resembling a U-shape; therefore, we fitted three linear segment models. Individual costs were assessed by dividing the survival time into the initial, continuing, and terminal phases by estimated thresholds, and the average medical cost for each phase was calculated. Results: Based on survival durations of 12 years or less, the initial phase occurred within 1.1-4.8 months after diagnosis, while the terminal phase was observed in 1.4-4.7 months before death. The length of these two phases increased with the increased survival time of the patients. Medical costs in these phases ranged from $4067-7431 and $3127-6114 (US dollars), respectively, regardless of the variations in survival time. However, the average costs in the continuing phase were higher for patients with a short survival time. Conclusions: This study highlights the cost dynamics in cancer care through a breakdown of the phases of survival. It suggests that through a more refined definition of the initial and terminal phases, the average cost in these stages increases, indicating the significant implications of the findings for resource allocation and tailored financial support strategies for patients with cancer with varying prognoses.

Risk of Subsequent Vitiligo in Transplant Recipients With Comorbid Graft-vs-Host Disease.

Importance: Vitiligo is a multifactorial, depigmenting skin disorder characterized by selective loss of melanocytes. Large-scale studies are lacking to determine the risk of vitiligo in transplant recipients with graft-vs-host disease (GVHD). Objective: To investigate the incidence rates and risk of vitiligo in patients who had received solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT) overall and by HSCT graft type and concomitant GVHD. Design, Setting, and Participants: This population-based cohort study included data from the National Health Insurance Service database of Korea for patients aged 20 years or older who had received a transplant (SOT or HSCT) between January 2010 and December 2017, with follow-up until December 2019. A cohort of age- and sex-matched (1:5) control individuals who did not receive a transplant was included for comparison. Data were analyzed from July 2021 to December 2021. Exposure: Transplant (SOT or HSCT) and GVHD. Main Outcomes and Measures: The main outcome was risk of vitiligo, assessed using multivariable Cox proportional hazards regression analyses adjusting for potential confounding factors. Results: The study included 23 829 patients who had undergone SOT or HSCT (62.78% male; mean [SD] age, 49.58 [11.59] years) and 119 145 age- and sex-matched controls. Patients who had undergone transplant had a significantly higher risk of vitiligo compared with controls (adjusted hazard ratio [AHR], 1.73; 95% CI, 1.35-2.22). Risk of vitiligo was also slightly higher in kidney transplant recipients and liver transplant recipients compared with the controls but was highest in HSCT recipients (AHR, 12.69; 95% CI, 5.11-31.50). Patients who had received allogeneic grafts (AHR, 14.43; 95% CI, 5.61-37.15), those who had received autologous grafts (AHR, 5.71; 95% CI, 1.20-3.18), those with comorbid GVHD (AHR, 24.09; 95% CI, 9.16-63.35), and those without GVHD (AHR, 8.21; 95% CI, 3.08-21.87) had a higher risk of vitiligo compared with controls. Conclusion and Relevance: In this study, risk of vitiligo was significantly higher in transplant recipients, especially in HSCT recipients and those with allogeneic grafts or comorbid GVHD. These findings provide new insights into the association between the risk of vitiligo and transplant and GVHD. Clinicians should be aware of these risks, implementing a multidisciplinary approach for monitoring.

Surgical margin status and role of adjuvant therapy in human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: We analyzed the difference in treatment results according to safety margin range and studied the role of adjuvant therapy in patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: A total of 279 patients with HPV+ OPSCC were included in this study. RESULTS: Surgical margin and T classification were significant prognostic factors related to death. The difference in locoregional recurrence was analyzed by dividing the safety margin into groups of <1, 1-5, and >5 mm. There was no significant difference in local-regional recurrence for T1-T2 lesions between the three groups. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors. CONCLUSIONS: In T1-T2 lesions without other risk factors, even with a safety margin ≥1 mm, adjuvant therapy can potentially be omitted. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors.

Quantifiable peptide library bridges the gap for proteomics based biomarker discovery and validation on breast cancer.

Mass spectrometry (MS) based proteomics is widely used for biomarker discovery. However, often, most biomarker candidates from discovery are discarded during the validation processes. Such discrepancies between biomarker discovery and validation are caused by several factors, mainly due to the differences in analytical methodology and experimental conditions. Here, we generated a peptide library which allows discovery of biomarkers in the equal settings as the validation process, thereby making the transition from discovery to validation more robust and efficient. The peptide library initiated with a list of 3393 proteins detectable in the blood from public databases. For each protein, surrogate peptides favorable for detection in mass spectrometry was selected and synthesized. A total of 4683 synthesized peptides were spiked into neat serum and plasma samples to check their quantifiability in a 10 min liquid chromatography-MS/MS run time. This led to the PepQuant library, which is composed of 852 quantifiable peptides that cover 452 human blood proteins. Using the PepQuant library, we discovered 30 candidate biomarkers for breast cancer. Among the 30 candidates, nine biomarkers, FN1, VWF, PRG4, MMP9, CLU, PRDX6, PPBP, APOC1, and CHL1 were validated. By combining the quantification values of these markers, we generated a machine learning model predicting breast cancer, showing an average area under the curve of 0.9105 for the receiver operating characteristic curve.

Prognostic role of surgical margins in patients undergoing transoral robotic surgery after neo-adjuvant chemotherapy.

PURPOSE: To define if positive and close surgical margins are associated to worse prognosis in patients who underwent transoral robotic surgery (TORS) after neoadjuvant chemotherapy (NCT). METHODS: A retrospective cohort study was carried out at a tertiary referral center. The primary outcome was local-regional control (LRC), and the results were summarized with hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: A total of 308 patients (median age: 62.0, IQR: 55.0-68.2) were included. Univariable analysis showed a significant reduced LRC for patients with positive margins (HR = 1.82, 95% CI: 1.02-3.24). However, they were not associated with worse LRC after adjusting for adverse tumor variables (HR = 0.81, 95% CI: 0.40-1.65). ROC analysis was performed on 123 patients with negative margins (AUC: 0.54) measuring an optimal threshold of 1.25 mm (sensitivity = 60.0%; specificity = 50.5%). Univariable analysis showed non-significant differences between close and wide negative margins (HR = 1.44, 95% CI: 0.59-3.54). CONCLUSIONS: A positive surgical margin is not an independent predictor of tumor control and survival. A threshold of 1.25 mm was identified as the most appropriate to define close margins, but no difference was measured after distinguishing negative margins in close and wide margins.

Investigation of somatic mutation profiles and tumor evolution of primary oropharyngeal cancer and sequential lymph node metastases using multiregional whole-exome sequencing.

Lymph node (LN) metastasis is an important factor in determining the treatment and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). Here, we compared the somatic mutational profiles and clonal evolution of primary and metastatic LNs using multiregion sequencing of human papilloma virus (HPV)-positive OPSCC and HPV-negative OPSCC. We performed high-depth whole-exome sequencing (200×) of 76 samples from 18 patients with OPSCC (10 HPV-positive and 8 HPV-negative), including 18 primary tumor samples, 40 metastatic LN samples, and 18 normal tissue samples. Among 40 metastatic LNs, 22 showed extranodal extension (ENE). Mutation profiles of HPV-positive OPSCC and HPV-negative OPSCC were similar to those reported previously. Somatic mutations in CDKN2A and TP53 were frequently detected in HPV-negative OPSCC. Somatic mutations in HPV-positive OPSCC samples showed APOBEC-related signatures. Somatic mutations from metastatic LNs showed a different pattern than the primary tumor. Somatic mutations acquired in the WNT pathway during metastasis showed a significant relationship with ENE. Clonal evolution analysis of primary and metastatic LNs showed that, in some cases, each metastatic LN originated from a different primary tumor sub-clone.

Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

Targeted deep sequencing reveals genomic alterations of actinic keratosis/cutaneous squamous cell carcinoma in situ and cutaneous squamous cell carcinoma.

Actinic keratosis (AK) and cutaneous squamous cell carcinoma in situ (CIS) are two of the most common precursors of cutaneous squamous cell carcinoma (cSCC). However, the genomic landscape of AK/CIS and the drivers of cSCC progression remain to be elucidated. The aim of our study was to investigate the genomic alterations between AK/CIS and cSCC in terms of somatic mutations and copy number alterations (CNAs). We performed targeted deep sequencing of 160 cancer-related genes with a median coverage of 515× for AK (N = 9), CIS (N = 9), cSCC lesions (N = 13), and matched germline controls from 17 patients. cSCC harboured higher abundance of total mutations, driver mutations and CNAs than AK/CIS. Driver mutations were found in TP53 (81%), NOTCH1 (32%), RB1 (26%) and CDKN2A (19%). All AK/CIS and cSCC lesions (93.5%), except two, harboured TP53 or NOTCH1 mutations, some of which were known oncogenic mutations or reported mutations in normal skin. RB1 driver mutations were found in CIS/cSCC (36.4%) but not in AK. CDKN2A driver mutations were found more frequently in cSCC (30.8%) than in AK/CIS (11.1%). Among recurrent (≥3 samples) CNAs (gain in MYC and PIK3CA/SOX2/TP63; loss in CDKN2A and RB1), MYC (8q) gain and CDKN2A (9p) loss were more frequently detected in cSCC (30.8%) than in AK/CIS (11.1%). Ultraviolet was responsible for the majority of somatic mutations in both AK/CIS and cSCC. Our study revealed that AK/CIS lesions harbour prevalent TP53 or NOTCH1 mutations and that additional somatic mutations and CNAs may lead to cSCC progression in AK/CIS lesions.

Incidence of Acute Endophthalmitis after Intravitreal Antivascular Endothelial Growth Factor Injection in Age-related Macular Degeneration.

PURPOSE: Antivascular endothelial growth factor (anti-VEGF) agents are routinely intravitreously injected to treat neovascular age-related macular degeneration (AMD). Postoperative endophthalmitis, a side effect after intravitreal anti-VEGF injection, has been reported to have a low incidence but may threaten vision. In this study, we aimed to analyze the incidence of acute endophthalmitis after intravitreal anti-VEGF injection and associated risk factors in patients with neovascular AMD in South Korea. METHODS: Using the health claims data recorded in the Korean National Health Insurance System database, we identified newly developed neovascular AMD cases from 2010 through 2019. Acute endophthalmitis was defined as a case of invasive treatment for accompanying symptoms. All statistical analyses were performed with a significance level p < 0.05. To find risk factors, we used univariate and multivariable Poisson regression. RESULTS: The overall incidence of acute endophthalmitis was 0.019% (p = 0.21) during the 10-year period: 0.025% for aflibercept injection and 0.014% for ranibizumab injection. The incidence was higher in metropolitan city residents than in Seoul (incidence rate ratio [IRR], 1.96; 95% confidence interval [CI], 1.02-3.79; p = 0.04) and was higher for aflibercept injections than for ranibizumab injections (IRR, 1.82; 95% CI, 1.17-2.82; p = 0.01). However, in multivariate analysis, only aflibercept injections showed a significant effect on the incidence of acute endophthalmitis (IRR, 1.80; 95% CI, 1.16-2.79; p = 0.01). CONCLUSIONS: The incidence of acute endophthalmitis after intravitreal anti-VEGF injections was generally low, and aflibercept was revealed as a significant risk factor.