Global characteristics and outcomes of autologous hematopoietic stem cell transplantation for newly diagnosed multiple myeloma: A study of the worldwide network for blood and marrow transplantation (WBMT).

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.

Activation of Wnt/ß-catenin signaling is critical for the tumorigenesis of choroid plexus.

BACKGROUND: Choroid plexus (ChP) is the secretory epithelial structure located in brain ventricles. Choroid plexus tumors (CPTs) are rare neoplasms predominantly occurring in young patients with intensified malignancy in children. CPT treatment is hindered by insufficient knowledge of the tumor pathology and limited availability of valid models. METHODS: Genomic and transcriptomic data from CPT patients were analyzed to identify the putative pathological pathway. Cellular and molecular techniques were employed to validate bioinformatic results in CPT patient samples. Pharmacologic inhibition of Wnt/ß-catenin signaling was assessed in CPT cells. Cell-based assays of ChP cell lines were performed following CRISPR-Cas9-derived knockout and over-expression of Wnt/ß-catenin pathway genes. 3D CPT model was generated through CRISPR-Cas9-derived knockout of APC. RESULTS: We discovered that Wnt/ß-catenin signaling is activated in human CPTs, likely as a consequence of large-scale chromosomal instability events of the CPT genomes. We demonstrated that CPT-derived cells depend on autocrine Wnt/ß-catenin signaling for survival. Constitutive Wnt/ß-catenin pathway activation, either through knock-out of the negative regulator APC or overexpression of the ligand WNT3A, induced tumorigenic properties in ChP 2D in vitro models. Increased activation of Wnt/ß-catenin pathway in ChP organoids, through treatment with a potent GSK3ß inhibitor, reduced the differentiation of mature ChP epithelia cells. Remarkably, the depletion of APC was sufficient to induce the oncogenic transformation of ChP organoids. CONCLUSIONS: Our research identifies Wnt/ß-catenin signaling as a critical driver of CPT tumorigenesis and provides the first 3D in vitro model for future pathological and therapeutic studies of CPT.

The ketogenic diet does not improve cardiac function and blunts glucose oxidation in ischaemic heart failure.

AIMS: Cardiac energy metabolism is perturbed in ischaemic heart failure and is characterized by a shift from mitochondrial oxidative metabolism to glycolysis. Notably, the failing heart relies more on ketones for energy than a healthy heart, an adaptive mechanism that improves the energy-starved status of the failing heart. However, whether this can be implemented therapeutically remains unknown. Therefore, our aim was to determine if increasing ketone delivery to the heart via a ketogenic diet can improve the outcomes of heart failure. METHODS AND RESULTS: C57BL/6J male mice underwent either a sham surgery or permanent left anterior descending coronary artery ligation surgery to induce heart failure. After 2 weeks, mice were then treated with either a control diet or a ketogenic diet for 3 weeks. Transthoracic echocardiography was then carried out to assess in vivo cardiac function and structure. Finally, isolated working hearts from these mice were perfused with appropriately 3H or 14C labelled glucose (5 mM), palmitate (0.8 mM), and ß-hydroxybutyrate (ß-OHB) (0.6 mM) to assess mitochondrial oxidative metabolism and glycolysis. Mice with heart failure exhibited a 56% drop in ejection fraction, which was not improved with a ketogenic diet feeding. Interestingly, mice fed a ketogenic diet had marked decreases in cardiac glucose oxidation rates. Despite increasing blood ketone levels, cardiac ketone oxidation rates did not increase, probably due to a decreased expression of key ketone oxidation enzymes. Furthermore, in mice on the ketogenic diet, no increase in overall cardiac energy production was observed, and instead, there was a shift to an increased reliance on fatty acid oxidation as a source of cardiac energy production. This resulted in a decrease in cardiac efficiency in heart failure mice fed a ketogenic diet. CONCLUSION: We conclude that the ketogenic diet does not improve heart function in failing hearts, due to ketogenic diet-induced excessive fatty acid oxidation in the ischaemic heart and a decrease in insulin-stimulated glucose oxidation.

Ketones provide an extra source of fuel for the failing heart without impairing glucose oxidation.

BACKGROUND: Cardiac glucose oxidation is decreased in heart failure with reduced ejection fraction (HFrEF), contributing to a decrease in myocardial ATP production. In contrast, circulating ketones and cardiac ketone oxidation are increased in HFrEF. Since ketones compete with glucose as a fuel source, we aimed to determine whether increasing ketone concentration both chronically with the SGLT2 inhibitor, dapagliflozin, or acutely in the perfusate has detrimental effects on cardiac glucose oxidation in HFrEF, and what effect this has on cardiac ATP production. METHODS: 8-week-old male C57BL6/N mice underwent sham or transverse aortic constriction (TAC) surgery to induce HFrEF over 3 weeks, after which TAC mice were randomized to treatment with either vehicle or the SGLT2 inhibitor, dapagliflozin (DAPA), for 4 weeks (raises blood ketones). Cardiac function was assessed by echocardiography. Cardiac energy metabolism was measured in isolated working hearts perfused with 5 mM glucose, 0.8 mM palmitate, and either 0.2 mM or 0.6 mM ß-hydroxybutyrate (ßOHB). RESULTS: TAC hearts had significantly decreased %EF compared to sham hearts, with no effect of DAPA. Glucose oxidation was significantly decreased in TAC hearts compared to sham hearts and did not decrease further in TAC hearts treated with high ßOHB or in TAC DAPA hearts, despite ßOHB oxidation rates increasing in both TAC vehicle and TAC DAPA hearts at high ßOHB concentrations. Rather, increasing ßOHB supply to the heart selectively decreased fatty acid oxidation rates. DAPA significantly increased ATP production at both ßOHB concentrations by increasing the contribution of glucose oxidation to ATP production. CONCLUSION: Therefore, increasing ketone concentration increases energy supply and ATP production in HFrEF without further impairing glucose oxidation.

Functional Protein Dynamics in a Crystal.

Proteins are molecular machines and to understand how they work, we need to understand how they move. New pump-probe time-resolved X-ray diffraction methods open up ways to initiate and observe protein motions with atomistic detail in crystals on biologically relevant timescales. However, practical limitations of these experiments demands parallel development of effective molecular dynamics approaches to accelerate progress and extract meaning. Here, we establish robust and accurate methods for simulating dynamics in protein crystals, a nontrivial process requiring careful attention to equilibration, environmental composition, and choice of force fields. With more than seven milliseconds of sampling of a single chain, we identify critical factors controlling agreement between simulation and experiments and show that simulated motions recapitulate ligand-induced conformational changes. This work enables a virtuous cycle between simulation and experiments for visualizing and understanding the basic functional motions of proteins.

Effect of Thrombin-Containing Local Hemostatics on Postoperative Spinal Epidural Hematoma in Biportal Endoscopic Spinal Surgery

Methods@#Patients with and without TCLH were assigned to groups A and B, respectively. POSEH between the two groups was compared morphometrically and symptomatically. The risk factors for symptomatic and morphometric POSEH in BESS were identified. @*Results@#The morphometric POSEH was greater in group B, and the difference was significant (p =0.019). The incidence of symptomatic POSEH was lower in group A with 4.6% (5/109) than in group B with 9.5% (9/95); however, the rate was not significantly different (p =0.136). The morphometric POSEH was classified into two small (hG1 and hG2) and large (hG3 and hG4) and were compared between groups A and B, and the difference was significant (p =0.02). In the multivariable logistic regression, nonuse of TCLH (p =0.004) and preoperative diagnosis of stenosis (p =0.016) were variables found to be significant risk factors of morphometric POSEH. @*Conclusions@#Severe compression of the thecal sac by POSEH is more common in patients without TCLH. The risk of hematoma formation was higher when bilateral decompression was needed and the cut bone surface was more exposed.

Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM. @*Materials and Methods@#Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed. @*Results@#Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05). @*Conclusion@#GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.

Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP / Journal of the Korean Cancer Association, 대한암학회지

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction

Background/Aims@#The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells. @*Methods@#Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors. The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively. @*Results@#We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function. @*Conclusions@#Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.

Polyposis of gastrointestinal tract after COVID-19 mRNA vaccination: a report of two cases

Cronkhite-Canada syndrome is a rare gastrointestinal polyposis syndrome with distinctive clinical features and endoscopic findings. Diagnosis can be challenging without suspicion, and the disease carries high mortality due to complications such as infection, gastrointestinal bleeding, and malignancies. This paper presents two cases of Cronkhite-Canada syndrome occurring after coronavirus disease 2019 (COVID-19) mRNA vaccination. Both cases exhibited typical clinical findings, including hypogeusia, onychodystrophy, alopecia, and weight loss. Typical polyposis in the gastrointestinal tract was confirmed through endoscopies. As symptomatic treatment did not improve the symptoms, corticosteroids were administered, and symptoms and laboratory test results improved immediately. The patients improved upon corticosteroids tapering. These cases illustrate typical presentations of Cronkhite-Canada syndrome and the course of the disease following corticosteroid treatment. Additionally, they suggest the possibility that Cronkhite-Canada syndrome may be triggered by COVID-19 mRNA vaccination.

The Destiny of the Subscapularis Tendon after Arthroscopic Supraspinatus Repair

Background@#The purpose of this study was to identify the changes in untreated subscapularis in patients who underwent supraspinatus repair and to evaluate the factors related to the changes in the subscapularis. @*Methods@#A cohort of patients who underwent isolated supraspinatus repair with preservation of the subscapularis was reviewed.Changes in the subscapularis, including any newly formed lesion and aggravation of an existing lesion, were evaluated 12 months postoperatively on magnetic resonance imaging along with an examination to identify causative factors after supraspinatus repair.Clinical scores were compared between patients with and without subscapularis changes. @*Results@#A total of 528 patients were reviewed. Changes in the subscapularis, including newly formed lesions and aggravation of an existing lesion, were shown in 90 patients (17.0%). Upon regression analysis, changes in the subscapularis were associated with the initial existence of a subscapularis lesion (grade I: p = 0.042, grade II: p = 0.025), an accompanying biceps lesion (p = 0.038), and a retear of the repaired supraspinatus (p = 0.024). No significant differences were shown in clinical scores between patients with and without subscapularis changes after supraspinatus repair. @*Conclusions@#Untreated asymptomatic subscapularis may undergo morphological changes even after repair of the torn supraspinatus. Preoperative subscapularis lesions, biceps long head pathology, and retears of the repaired supraspinatus were associated with subscapularis pathology in patients who underwent supraspinatus repair.

Comparison of the Usefulness of ComputerAssisted Three-Dimensional Analysis and WeightBearing Radiographs in Ankle Osteoarthritis

Background@#To evaluate the degree of deformation in patients with ankle osteoarthritis (OA), it is essential to measure the threedimensional (3D), in other words, stereoscopic alignment of the ankle, subtalar, and foot arches. Generally, measurement of radiological parameters use two-dimensional (2D) anteroposterior and lateral radiographs in a weight-bearing state; however, computeraided 3D analysis (Disior) using weight-bearing cone-beam computed tomography (CBCT) has recently been introduced. @*Methods@#In this study, we compared the 2D human radiographic method with a stereoscopic image in patients with ankle arthritis. We enrolled 57 patients diagnosed with OA (28 left and 29 right) and obtained both standing radiographs and weight-bearing CBCT. Patients were divided by the Takakura stage. The interclass correlation coefficient (ICC) for each result was confirmed. @*Results@#On the ICC between 2D radiographs and 3D analysis, the tibiotalar surface angle and lateral talo-1st metatarsal angle showed a good ICC grade (> 0.6), while other parameters did not have significant ICC results. Three-dimension was superior to radiographs in terms of statistical significance. @*Conclusions@#We demonstrated that 2D and stereoscopic images are useful for the diagnosis of OA. Our study also confirmed that the radiographic features affected by ankle OA varied. However, according to the results, the typical radiography is not sufficient to diagnose and determine a treatment plan for ankle OA. Therefore, the method of using 3D images should be considered.

Clinical and Radiological Outcomes of Computer-Assisted Navigation in Primary Total Knee Arthroplasty for Patients with Extra-articular Deformity: Systematic Review and Meta-Analysis

Background@#Computer-assisted navigation surgery (CAS) during primary total knee arthroplasty (TKA) may help improve outcomes for patients with extra-articular deformity (EAD); however, this has not been extensively studied. Therefore, we aimed to investigate the clinical and radiological outcomes following primary TKA using CAS in patients with EAD. @*Methods@#We searched Medline, Embase, and the Cochrane Library up to March 3, 2023 for studies investigating surgical outcomes of using the navigation system for TKA to treat patients with EAD. From 14 studies, 539 knees with EAD that underwent navigation TKA were enrolled. We investigated the knee range of motion (ROM), outcome scores at final follow-up (Knee Society Score [KSS] and Knee Functional Score [KFS]), and pre- and postoperative mechanical hip-knee-ankle (mHKA) angle using lower extremity scanogram. The meta-analysis was based on the single-arm method, and all data were pooled using a random-effects model. @*Results@#Following our meta-analyses, the mean knee ROM changed from 87.0° (95% confidence interval [CI], 75.9°–98.1°) preoperatively to 109.4° (95% CI, 97.9°–120.8°) postoperatively. The adjusted KSS was 93.45 points (95% CI, 88.36–98.54 points), and the adjusted KFS was 91.57 points (95% CI, 86.80–96.33 points) in knees with EAD that underwent CAS-TKA. As a radiological outcome, the mHKA angle changed from 169.53° (95% CI, 166.90°–172.16°) preoperatively to 178.81° (95% CI, 178.31°–179.30°) postoperatively. @*Conclusions@#CAS-TKA yielded positive clinical results and demonstrated a satisfactory alignment of the lower limb’s mechanical axis. CAS-TKA showed promise for primary TKA procedures, demonstrating favorable clinical and radiological outcomes even in complex cases involving EAD.

What is the Optimal Nail Length to Treat Osteoporotic Subtrochanteric Fractures?A Finite Element Analysis

Background@#Operative management with intramedullary nail fixation remains the definitive treatment of choice for osteoporotic subtrochanteric (ST) fractures; however, there remains no consensus regarding the proper nail length. We aimed to use 3-dimensional finite element (FE) analysis to determine the optimal nail length for the safe fixation of osteoporotic ST fractures. @*Methods@#Nine modes of FE models were constructed using 9 different lengths of cephalomedullary nails (short nails: 170, 180, and 200 mm; long nails: 280, 300, 320, 340, 360, and 380 mm) from the same company. The interfragmentary motion was analyzed. Additionally, the peak von Mises stress (PVMS) in the cortical bone, cancellous bone of the femoral head, and the nail were measured, and the yielding risk for each subject was investigated. @*Results@#Long nails were associated with less interfragmentary motion. In the cortical bone, the PVMS of short nails was observed at the distal locking screw holes of the femoral medial cortex; however, in long nails, the PVMS was observed at the lag screw holes on the lateral cortex. The mean yielding risk of long nails was 40.1% lower than that of short nails. For the cancellous bone of the femoral head, the PVMS in all 9 FE models was in the same area: at the apex of the femoral head. There was no difference in the yielding risk between short and long nails. For implants, the PVMS was at the distal locking screw hole of the nail body in the short nails and the nail body at the fracture level in the long nails. The mean yielding risk was 74.9% lower for long nails than that for short nails. @*Conclusions@#Compared to short nails, long nails with a length of 320 mm or more showed less interfragmentary motion and lower yielding risk in low-level osteoporotic ST fractures. The FE analysis supports long nails as a safer option than short nails, especially for treating transverse-type low-level osteoporotic ST fractures.

Comparison of an Endoscopic Scoring System and the Simplified Magnetic Resonance Index of Activity in Patients with Small Bowel Crohn’s Disease

Background/Aims@#The newly derived simplified magnetic resonance index of activity (MARIAs) has not been verified in comparison to balloon-assisted enteroscopy (BAE) for patients with small bowel Crohn’s disease (CD). We studied the correlation of MARIAs with simple endoscopic scores for CD (SES-CD) of the ileum based on magnetic resonance enterography (MRE) and BAE in patients with small bowel CD. @*Methods@#Fifty patients with small bowel CD who underwent BAE and MRE concurrently within 3 months from September 2020 to June 2021 were enrolled in the study. The primary outcome was the correlation between the active score of ileal SES-CD (ileal SES-CDa)/ileal SES-CD and MARIAs based on BAE and MRE. The cutoff value for MARIAs identifying endoscopically active/ severe disease, defined as ileal SES-CDa/ileal SES-CD of 5/7 or more, was analyzed. @*Results@#Ileal SES-CDa/ileal SES-CD and MARIAs showed strong associations (R=0.76, p<0.001; R=0.78, p<0.001). The area under the receiver operating characteristic curve of MA-RIAs for ileal SES-CDa ≥5 and ileal SES-CD ≥7 was 0.92 (95% confidence interval, 0.88 to 0.97) and 0.92 (95% confidence interval, 0.87 to 0.97). The cutoff value of MARIAs for detecting active/ severe disease was 3. A MARIAs index value of ≥3 identified ileal SES-CDa ≥5 with a sensitiv-ity of 85% and specificity of 87% and detected ileal SES-CD ≥7 with a sensitivity of 87% and specificity of 86%. @*Conclusions@#This study validated the applicability of MARIAs compared to BAE-based ileal SES-CDa/SES-CD.

Analysis of Characteristics and Risk Factors of Patients with Single Gastric Cancer and Synchronous Multiple Gastric Cancer among 14,603 Patients

Background/Aims@#Synchronous multiple gastric cancer (SMGC) accounts for approximately 6% to 14% of gastric cancer (GC) cases. This study aimed to identify risk factors for SMGC. @*Methods@#A total of 14,603 patients diagnosed with GC were prospectively enrolled. Data including age, sex, body mass index, smoking, alcohol consumption, family history, p53 expression, microsatellite instability, cancer classification, lymph node metastasis, and treatment were collected. Risk factors were analyzed using logistic regression analysis between a single GC and SMGC. @*Results@#The incidence of SMGC was 4.04%, and that of early GC (EGC) and advanced GC (AGC) was 5.43% and 3.11%, respectively. Patients with SMGC were older (65.33 years vs 61.75 years, p<0.001) and more likely to be male. Lymph node metastasis was found in 27% of patients with SMGC and 32% of patients with single GC. Multivariate analysis showed that SMGC was associated with sex (male odds ratio [OR], 1.669; 95% confidence interval [CI], 1.223 to 2.278; p=0.001), age (≥65 years OR, 1.532; 95% CI, 1.169 to 2.008; p=0.002), and EGC (OR, 1.929; 95% CI, 1.432 to 2.600; p<0.001). Survival rates were affected by Lauren classification, sex, tumor size, cancer type, distant metastasis, and venous invasion but were not related to the number of GCs. However, the survival rate of AGC with SMGC was very high. @*Conclusions@#SMGC had unique characteristics such as male sex, older age, and EGC, and the survival rate of AGC, in which the intestinal type was much more frequent, was very good (Trial registration number: NCT04973631).

Prognostic Factors for Predicting Post-COVID-19 Condition in Patients With COVID-19 in an Outpatient Setting

Background@#Although data on post-coronavirus disease 2019 (COVID-19) conditions are extensive, the prognostic factors affecting symptom duration in non-hospitalized patients with COVID-19 are currently not well known. We aimed to investigate the various prognostic factors affecting symptom duration among outpatients with COVID-19. @*Methods@#Data were analyzed from 257 patients who were diagnosed with mild COVID-19 and visited the ‘post-COVID-19 outpatient clinic’ between April and December 2022 after a mandatory isolation period. The symptom duration was measured from diagnosis to symptom resolution. Laboratory and pulmonary function test results from their first visit were collected. @*Results@#The mean age of patients was 55.7 years, and the median symptom duration was 57 days. The development of post-COVID-19 conditions (> 12 weeks) were significantly correlated with not using antiviral drugs, leukocytosis (white blood cell > 10,000/µL), lower 25(OH)D 3 levels, forced vital capacity (FVC) < 90% predicted, and presence of dyspnea and anxiety/depression. Additionally, in multivariable Cox regression analysis, not using antiviral drugs, lower 25(OH)D 3 levels, and having dyspnea were poor prognostic factors for longer symptom duration. Particularly, vitamin D deficiency (< 20 ng/mL) and not using antivirals during the acute phase were independent poor prognostic factors for both post-COVID-19 condition and longer symptom duration. @*Conclusion@#The non-use of antivirals, lower 25(OH)D 3 levels, leukocytosis, FVC < 90% predicted, and the presence of dyspnea and anxiety/depression symptoms could be useful prognostic factors for predicting post-COVID-19 condition in outpatients with COVID-19. We suggest that the use of antiviral agents during the acute phase and vitamin D supplements might help reduce COVID-19 symptom duration.

Comparative Effectiveness of Personal Sound Amplification Products Versus Hearing Aids for Unilateral Hearing Loss: A Prospective Randomized Crossover Trial

Background@#This study compared hearing outcomes with use of personal sound amplification products (PSAPs) and hearing aids (HAs) in patients with moderate to moderately severe unilateral hearing loss. @*Methods@#Thirty-nine participants were prospectively enrolled, and randomly assigned to use either one HA (basic or premium type) or one PSAP (basic or high-end type) for the first 8 weeks and then the other device for the following 8 weeks. Participants underwent a battery of examinations at three visits, including sound-field audiometry, word recognition score (WRS), speech perception in quiet and in noise, real-ear measurement, and self-report questionnaires. @*Results@#Functional gain was significantly higher with HAs across all frequencies (P < 0.001). While both PSAPs and HAs improved WRS from the unaided condition, HAs were superior to PSAPs. The speech recognition threshold in quiet conditions and signal-to-noise ratio in noisy conditions were significantly lower in the HA-aided condition than in the PSAP-aided condition, and in the PSAP-aided condition than in the unaided condition. Subjective satisfaction also favored HAs than PSAPs in questionnaires, Abbreviated Profile of Hearing Aid Benefit, International Outcome Inventory for Hearing Aids, and Host Institutional Questionnaire. @*Conclusion@#While PSAPs provide some benefit for moderate to moderately severe unilateral hearing loss, HAs are more effective. This underscores the potential role of PSAPs as an accessible, affordable first-line intervention in hearing rehabilitation, particularly for individuals facing challenges in accessing conventional HAs.

Characteristics According to Frailty Status Among Older Korean Patients With Hypertension

Background@#As the prevalence of hypertension increases with age and the proportion of the older population is also on the rise, research on the characteristics of older hypertensive patients and the importance of frailty is necessary. This study aimed to identify clinical characteristics of older hypertension in Korea and to investigate these characteristics based on frailty status. @*Methods@#The HOW to Optimize eLDerly systolic BP (HOWOLD-BP) is a prospective, multicenter, open-label, randomized clinical trial that aims to compare intensive (target systolic blood pressure [SBP] ≤ 130 mmHg) with standard (target SBP ≤ 140 mmHg) treatment to reduce cardiovascular events in older hypertensive Korean patients aged ≥ 65 years. Data were analyzed through a screening assessment of 2,085 patients recruited from 11 university hospitals. Demographic, functional (physical and cognitive), medical history, laboratory data, quality of life, and medication history of antihypertensive drugs were assessed. @*Results@#The mean age was 73.2 years (standard deviation ± 5.60), and 48.0% (n = 1,001) were male. Prevalent conditions included dyslipidemia (66.5%), obesity (body mass index ≥ 25 kg/m 2 , 53.6%), and diabetes (28.9%). Dizziness and orthostatic hypotension were self-reported by 1.6% (n = 33) and 1.2% (n = 24), respectively. The majority of patients were on two antihypertensive drugs (48.4%), while 27.5% (n = 574) and 20.8% (n = 433) were on 1 and 3 antihypertensive medications, respectively. Frail to pre-frail patients were older and also tended to have dependent instrumental activities of daily living, slower gait speed, weaker grip strength, lower quality of life, and lower cognitive function. The frail to pre-frail group reported more dizziness (2.6% vs. 1.2%, P < 0.001) and had concerning clinical factors, including lower glomerular filtration rate, more comorbidities such as diabetes, stroke, and a history of admission. Frail to pre-frail older hypertensive patients used slightly more antihypertensive medications than robust older hypertensive patients (1.95 vs. 2.06, P = 0.003). Pre-frail to frail patients often chose beta-blockers as a third medication over diuretics. @*Conclusion@#This study described the general clinical characteristics of older hypertensive patients in Korea. Frail hypertensive patients face challenges in achieving positive clinical outcomes because of multifactorial causes: they are older, have more morbidities, decreased function, lower quality of life and cognitive function, and take more antihypertensive medications. Therefore, it is essential to comprehensively evaluate and monitor diseaserelated or drug-related adverse events more frequently during regular check-ups, which is necessary for pre-frail to frail older patients with hypertension.

Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.