Histologic features and predicting prognosis in ulcerative colitis patients with mild endoscopic activity

Background/Aims@#We aimed to evaluate the histologic features predictive of prognosis and correlate them with endoscopic findings in patients with ulcerative colitis (UC) having complete or partial mucosal healing (MH). @*Methods@#We prospectively collected and reviewed data from patients with UC who underwent colonoscopy or sigmoidoscopy with biopsy. Complete and partial MH were defined as Mayo endoscopic subscores (MESs) of 0 and 1, respectively. Histologic variables, including the Nancy index (NI), predicting disease progression (defined as the need for medication upgrade or hospitalization/surgery), were evaluated and correlated with endoscopic findings. @*Results@#Overall, 441 biopsy specimens were collected from 194 patients. The average follow-up duration was 14.7 ± 7.4 months. There were 49 (25.3%) and 68 (35.1%) patients with MESs of 0 and 1, respectively. Disease progression occurred only in patients with an MES of 1. NI ≥ 3 was significantly correlated with disease progression during follow-up. Mucosal friability on endoscopy was significantly correlated with NI ≥ 3 (61.1% in NI < 3 vs. 88.0% in NI ≥ 3; p = 0.013). @*Conclusions@#Histological activity can help predict the prognosis of patients with UC with mild endoscopic activity. Mucosal friability observed on endoscopy may reflect a more severe histological status, which can be a risk factor for disease progression.

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.

Midterm Outcomes after Operative Management of Hawkins Type III Talar Neck Fractures

Background@#This study aims to report the midterm outcomes after surgical treatment of Hawkins Classification III Talar neck fractures. @*Methods@#From March 2010 to April 2022, among a total of 155 patients who visited our hospital with talus fractures, 31 patients underwent surgical treatment for Hawkins classification III talar neck fractures. The inclusion criteria comprised patients with a symptom duration of over 1 year who were available for outpatient follow-up and underwent magnetic resonance imaging (MRI) follow-up 2 months after surgery. Exclusion criteria included patients without preoperative ankle periarticular arthritis, and a total of 27 patients were enrolled. Traffic accidents and falls accounted for 86% of 23 cases, open fractures were 8 cases, and the mean follow-up period was 34.10 months (range, 12–80 months). Clinical outcomes were measured by American Orthopaedic Foot and Ankle Society (AOFAS) score and Foot function index (FFI), and radiological results were obtained using simple radiographs before and after surgery and MRI at 2 months postoperatively to confirm bone union and complications. @*Results@#Complete bone union was achieved in all cases, and the mean duration of union was 4.9 months (range, 4–6 months) and there were no nonunion and varus malunion. At the final follow-up, the mean AOFAS score was 80.18 points (range, 36–90 points) and the mean FFI score was 31.43 points (range, 10–68 points), showing relatively good clinical outcomes. There were 15 cases of avascular necrosis, 6 cases of traumatic arthritis of the ankle joint, 6 cases of irritation of the posterior tibial nerve, and 4 cases of wound problems. @*Conclusions@#Hawkins classification III talar neck fractures are mostly caused by high-energy injuries and have a relatively poor prognosis due to the high incidence of complications such as avascular necrosis or posttraumatic arthritis. However, if correct anatomical reduction and rigid internal fixation are performed within a short time after the injury, good results can be expected.

Difficult Small Bowel Bleeding in Surgical View

diagnostic modalities in SBB are performed. However, the small bowel is beyond the reach of these diagnostic modalities. A large amount of bleeding in GIB is a key factor leading to a poor prognosis. Appropriate and prompt diagnostic and treatment strategies are needed. Several diagnostic and management algorithms have been proposed. However, the processing of algorithm is complex and frequent mistakes are happened. Because of surgical aspects and sudden or gradual development of hemodynamic instability in SBB, algorithms considering surgical role and treatment have been published. The intra-operative enteroscopy (IOE) is a gold-standard method for detecting lesions in SBB. The primary goal of IOE is to detect specific bleeding focus in SBB. The determining the resection range is the secondary goal. In most cases in SBB, segmental resection is treatment of choice. However, in bleeding distal duodenum from distal to the ampulla of Vater to Treitz ligament, pancreas preserving distal duodenectomy could be performed. In terminal ileum bleeding, after resection of pathologic bowel, the reconstruction option is ileo-colic anastomosis or end enterostomy. Because of frequently developed postoperative morbidity and mortality, post-operative critical care is perfectly fit for an acute care surgeon’s role. Therefore, in the entire management process, an interprofessional team or multidisciplinary approach is critical for improving the quality of care of SBB and decreasing mistakes.

Incidence Rate and Risk Factors of Intraocular Lens Dislocation in South Korea

Purpose@#To analyze the incidence rate and risk factors of intraocular lens dislocation in South Korea from 2002 to 2020 using Health Insurance Review and Assessment Service data. @*Methods@#This study included 15% of patients aged > 40 years had pseudophakia or intraocular lens primary implantation codes during 2002-2020 (737,606 patients). The annual incidence rate and risk factors of intraocular lens dislocation during 2002-2020 were analyzed. @*Results@#The mean annual incidence rate of intraocular lens dislocation during 2002-2020 was 0.20 ± 0.7%. The annual incidence rate increased significantly from 0.17% in 2002 to 0.34% in 2020 (p 0.05). The annual mean incidence rate for men was 0.35 ± 0.13% and an increasing trend was found (p 0.05). @*Conclusions@#The mean annual incidence rate of intraocular lens dislocation in South Korea was 0.2 ± 0.7%, and it showed an increasing trend, among men. High myopia, uveitis, retinitis pigmentosa, glaucoma, pseudoexfoliative glaucoma and previous vitreoretinal surgery significantly increased the risk of intraocular lens dislocation.

Unenhanced Breast MRI With Diffusion-Weighted Imaging for Breast Cancer Detection: Effects of Training on Performance and Agreement of Subspecialty Radiologists

Objective@#To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI). @*Materials and Methods@#A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm 2 was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive.The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC). @*Results@#Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4–79.9), 90.8% (95% CI: 85.6–94.2), and 83.5% (95% CI: 78.6–87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8–97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9–89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1–79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52–0.63) before training and 0.68 (95% CI: 0.62–0.74) after training, with a difference of 0.11 (95% CI: 0.02–0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69–0.74) before training and 0.79 (95% CI: 0.76–0.80) after training (P = 0.002). @*Conclusion@#Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.

Combination therapy of liothyronine and levothyroxine for hypothyroidism-induced dilated cardiomyopathy

Thyroid hormone plays a vital role in regulating human metabolism. They affect the functions of major organs, such as the brain, liver, skeletal muscle, and heart. Hypothyroidism can lead to dilated cardiomyopathy and decreased heart function. In this report, we describe a case of a teenage boy who developed dilated cardiomyopathy due to hypothyroidism and was considered to undergo heart transplantation. Levothyroxine monotherapy was initiated but produced no improvement. Thereafter, a combination therapy of liothyronine and levothyroxine was administered, and heart function was gradually restored; he recovered completely after 6 months. Cardiac myocytes respond more specifically to liothyronine than to levothyroxine. Therefore, we suggest that liothyronine and levothyroxine combination therapy should be considered rather than levothyroxine monotherapy for hypothyroidism accompanied by heart disease.

Combination of the LARS1 Inhibitor, BC-LI-0186 with a MEK1/2 Inhibitor Enhances the Anti-Tumor Effect in Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth and proliferation by growth factor coordination and amino acid availability. Leucyl-tRNA synthetase 1 (LARS1) senses the intracellular leucine concentration and mediates amino acid-induced activation of mTORC1. Thus, LARS1 inhibition could be useful in cancer treatment. However, the fact that mTORC1 can be stimulated by various growth factors and amino acids suggests that LARS1 inhibition alone has limitations in inhibiting cell growth and proliferation. We investigated the combined effects of BC-LI-0186, a LARS1 inhibitor, and trametinib, an MEK inhibitor, on non–small cell lung cancer (NSCLC). @*Materials and Methods@#Protein expression and phosphorylation were observed by immunoblotting, and genes differentially expressed between BC-LI-0186–sensitive and –resistant cells were identified by RNA sequencing. The combined effect of the two drugs was inferred from the combination index values and a xenograft model. @*Results@#LARS1 expression was positively correlated with mTORC1 in NSCLC cell lines. BC-LI-0186 treatment of A549 and H460 cells maintained in media supplemented with fetal bovine serum revealed paradoxical phosphorylation of S6 and activation of mitogen- activated protein kinase (MAPK) signaling. Compared with BC-LI-0186–sensitive cells, –resistant cells showed enrichment of the MAPK gene set. The combination of trametinib and BC-LI-0186 inhibited the phosphorylation of S6, MEK, and extracellular signal-regulated kinase and their synergistic effects were confirmed in a mouse xenograft model. @*Conclusion@#The combination of BC-LI-0186 and trametinib inhibited the non-canonical mTORC1-activating function of LARS1. Our study demonstrated a new therapeutic approach for NSCLC without targetable driver mutations.

Virulence-associated Genome Sequences of Pasteurella canis and Unique Toxin Gene Prevalence of P. canis and Pasteurella multocida Isolated from Humans and Companion Animals

Background@#Comparative analysis of virulence factors (VFs) between Pasteurella canis and Pasteurella multocida are lacking, although both cause zoonotic infections. We determined the virulence-associated genome sequence characteristics of P. canis and assessed the toxin gene prevalence unique to P. canis among clinical isolates of P. canis and P. multocida. @*Methods@#We selected 10 P. canis and 16 P. multocida whole-genome sequences (WGSs) from the National Center for Biotechnology database. The VFanalyzer tool was used to estimate P. canis-characteristic VFs. Amino acid sequences of VFs were compared with multiple-aligned sequences. The genome structure containing P. canis-characteristic and adjacent loci was compared to the corresponding P. multocida genome structure. After designing primer sequences and assessing their accuracy, we examined the gene prevalence of the P. canis-characteristic VFs using PCR among clinical isolates of P. multocida and P. canis. @*Results@#Using VFanalyzer, we found virulence-associated cytolethal distending toxin (cdt)A–cdtB–cdtC loci common to all P. canis WGSs that were not found in P. multocida WGSs. Similarities in the multiple alignments of CdtA–CdtB–CdtC amino acid sequences were found among the 10 P. canis WGSs. Shared or similar loci around cdtA–cdtB–cdtC were identified between the P. canis and P. multocida genome structures. The PCR-based cdtA–cdtB–cdtC prevalence differed for P. canis and P. multocida clinical isolates. @*Conclusions@#P. canis-specific cdtA–cdtB–cdtC prevalence was identified among clinical isolates. These three loci may be unique toxin genes and promising targets for the rapid identification of P. canis in clinical settings.

Rapid Targeted Sequencing Using Dried Blood Spot Samples for Patients With Suspected Actionable Genetic Diseases

Background@#New genome sequencing technologies with enhanced diagnostic efficiency have emerged. Rapid and timely diagnosis of treatable rare genetic diseases can alter their medical management and clinical course. However, multiple factors, including ethical issues, must be considered. We designed a targeted sequencing platform to avoid ethical issues and reduce the turnaround time. @*Methods@#We designed an automated sequencing platform using dried blood spot samples and a NEOseq_ACTION panel comprising 254 genes associated with Mendelian diseases having curable or manageable treatment options. Retrospective validation was performed using data from 24 genetically and biochemically confirmed patients. Prospective validation was performed using data from 111 patients with suspected actionable genetic diseases. @*Results@#In prospective clinical validation, 13.5% patients presented with medically actionable diseases, including short- or medium-chain acyl-CoA dehydrogenase deficiencies (N=6), hyperphenylalaninemia (N=2), mucopolysaccharidosis type IVA (N=1), alpha thalassemia (N=1), 3-methylcrotonyl-CoA carboxylase 2 deficiency (N=1), propionic acidemia (N=1), glycogen storage disease, type IX(a) (N=1), congenital myasthenic syndrome (N=1), and citrullinemia, type II (N=1). Using the automated analytic pipeline, the turnaround time from blood collection to result reporting was <4 days. @*Conclusions@#This pilot study evaluated the possibility of rapid and timely diagnosis of treatable rare genetic diseases using a panel designed by a multidisciplinary team. The automated analytic pipeline maximized the clinical utility of rapid targeted sequencing for medically actionable genes, providing a strategy for appropriate and timely treatment of rare genetic diseases.

Exploring the Association between Thyroid Function and Frailty: Insights from Representative Korean Data

Background@#This study investigates the association between thyroid function and frailty in the old patients using representative data. @*Methods@#The study was conducted using data from the Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015. The study population included 2,416 participants aged 50 years and older with available thyroid function test data. Frailty assessment was performed using the Fried frailty phenotype. The prevalence of frailty was analyzed across different thyroid diseases and thyroid function parameters. @*Results@#The significant association between thyroid dysfunction and frailty was observed in overt hyperthyroidism and subclinical hyperthyroidism. After adjusting for various factors, the association between thyroid dysfunction and frailty remained significant. On the other hand, overt hypothyroidism did not show a significant association with frailty in the adjusted analysis. For individuals with overt hyperthyroidism and subclinical hyperthyroidism, higher levels of free thyroxine (FT4) were significantly associated with an increased risk of frailty (aOR >999; 95% CI, >999 to 999). Among individuals with overt hypothyroidism, lower level of FT4 levels and high thyrotropin (TSH) levels showed a significant association with frailty risk (FT4: aOR, <0.01; TSH: aOR, 999). In participants with subclinical hypothyroidism, there were no significant associations between parameters for thyroid and frailty risk. @*Conclusion@#These findings suggest that thyroid dysfunction, particularly overt hyperthyroidism and subclinical hyperthyroidism, may be associated with an increased risk of frailty in the old patients.

Promising Therapeutic Effectsof Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanisms

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue diseaseILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone.Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

A Novel Acremonium Species Isolated from Air Samples in Korea

The aim of this study was to characterize a new fungal species, Acremonium conglutinatum, isolated from air samples collected in Wando, South Korea. Phylogenetic analysis based on the internal transcribed spacer and large subunit regions revealed its unique position within the genus Acremonium. The isolated strain displayed distinct morphological characteristics, including ellipsoid or bent-ellipsoid conidia formed in clusters on the phialides. These features differentiate the new species from closely related species within the genus. This study describes the morphological and molecular characteristics of A. conglutinatum and emphasizes its phylogenetic relationships with other Acremonium spp. The identification of this novel species contributes to our understanding of the diversity and ecological role of Acremonium.

Compositional changes in fecal microbiota associated with clinical phenotypes and prognosis in Korean patients with inflammatory bowel disease

Background/Aims@#The fecal microbiota of Korean patients with inflammatory bowel disease (IBD) was investigated with respect to disease phenotypes and taxonomic biomarkers for diagnosis and prognosis of IBD. @*Methods@#Fecal samples from 70 ulcerative colitis (UC) patients, 39 Crohn’s disease (CD) patients, and 100 healthy control individuals (HC) were collected. The fecal samples were amplified via polymerase chain reaction and sequenced using Illumina MiSeq. The relationships between fecal bacteria and clinical phenotypes were analyzed using the EzBioCloud database and 16S microbiome pipeline. @*Results@#The alpha-diversity of fecal bacteria was significantly lower in UC and CD (P<0.05) compared to that in HC. Bacterial community compositions in UC and CD were significantly different from that of HC according to Bray-Curtis dissimilarities, and there was also a difference between community composition in UC and CD (P=0.01). In UC, alpha-diversity was further decreased when the disease was more severe and the extent of disease was greater, and community composition significantly differed depending on the extent of the disease. We identified 9 biomarkers of severity and 6 biomarkers of the extent of UC. We also identified 5 biomarkers of active disease and 3 biomarkers of ileocolonic involvement in CD. Lachnospiraceae and Ruminococcus gnavus were biomarkers for better prognosis in CD. @*Conclusions@#The fecal microbiota profiles of IBD patients were different from those of HC, and several bacterial taxa may be used as biomarkers to determine disease phenotypes and prognosis. These data may also help discover new therapeutic targets for IBD.

Digital Breast Tomosynthesis Plus Ultrasound Versus Digital Mammography Plus Ultrasound for Screening Breast Cancer in Women With Dense Breasts

Objective@#To compare the outcomes of digital breast tomosynthesis (DBT) screening combined with ultrasound (US) with those of digital mammography (DM) combined with US in women with dense breasts. @*Materials and Methods@#A retrospective database search identified consecutive asymptomatic women with dense breasts who underwent breast cancer screening with DBT or DM and whole-breast US simultaneously between June 2016 and July 2019. Women who underwent DBT + US (DBT cohort) and DM + US (DM cohort) were matched using 1:2 ratio according to mammographic density, age, menopausal status, hormone replacement therapy, and a family history of breast cancer. The cancer detection rate (CDR) per 1000 screening examinations, abnormal interpretation rate (AIR), sensitivity, and specificity were compared. @*Results@#A total of 863 women in the DBT cohort were matched with 1726 women in the DM cohort (median age, 53 years; interquartile range, 40–78 years) and 26 breast cancers (9 in the DBT cohort and 17 in the DM cohort) were identified. The DBT and DM cohorts showed comparable CDR (10.4 [9 of 863; 95% confidence interval {CI}: 4.8–19.7] vs. 9.8 [17 of 1726;95% CI: 5.7–15.7] per 1000 examinations, respectively; P = 0.889). DBT cohort showed a higher AIR than the DM cohort (31.6% [273 of 863; 95% CI: 28.5%–34.9%] vs. 22.4% [387 of 1726; 95% CI: 20.5%–24.5%]; P < 0.001). The sensitivity for both cohorts was 100%. In women with negative findings on DBT or DM, supplemental US yielded similar CDRs in both DBT and DM cohorts (4.0 vs. 3.3 per 1000 examinations, respectively; P = 0.803) and higher AIR in the DBT cohort (24.8% [188 of 758; 95% CI: 21.8%–28.0%] vs. 16.9% [257 of 1516; 95% CI: 15.1%–18.9%; P < 0.001). @*Conclusion@#DBT screening combined with US showed comparable CDR but lower specificity than DM screening combined with US in women with dense breasts.

Clinical features of children with drug poisoning in a single emergency department in Goyang, Korea

Purpose@#Pediatric drug poisoning is a frequent reason for emergency department (ED) visits. Considering the increasing number of mental illnesses in adolescents, it has become a serious public health problem. We aimed to investigate the drug poisoning in the ED. @*Methods@#We retrospectively analyzed children aged 1-17 years with diagnostic codes related to drug poisoning who visited the ED from January 1, 2010 through October 7, 2022. Exclusion criteria were non-pharmaceutical poisoning, insufficient data, and poisoning via respiratory, dermal or ocular route. Baseline characteristics, clinical manifestations, and outcomes of drug poisoning were analyzed in the study population, according to intention of poisoning and drug category. @*Results@#A total of 197 cases of 161 children were analyzed. Compared with non-intentional poisoning, intentional poisoning was associated a higher age, a longer time from ingestion to visit, and higher proportions of girls, antipyretics/analgesics or psychotropic drugs, symptoms related to the gastrointestinal, neurologic or cardiopulmonary systems (P = 0.034), psychiatric comorbidity, multiple drug ingestion, suicide attempt, decontamination (P = 0.017), the use of antidote, history of drug poisoning, and hospitalization (P = 0.004; all other Ps < 0.001). Acetaminophen, a representative of antipyretics/analgesics, was associated with a longer time from ingestion to visit and higher proportions of girls (P = 0.004), the presence of initial gastrointestinal symptoms, suicide attempt (P = 0.001), the use of antidote, and hospitalization (all other Ps < 0.001). Psychotropic drug was associated with higher proportions of psychiatric comorbidity (P < 0.001) and multiple drug ingestion (P = 0.012). @*Conclusion@#This study will enable pediatricians or emergency physicians to obtain an overview of the management of drug poisoning in EDs.

Predictive role of absolute lymphocyte count in daratumumab-treated patients with relapsed/ refractory multiple myeloma

Background/Aims@#Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. @*Methods@#Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). @*Results@#Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). @*Conclusions@#Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Role of Doppler US and elastography prior to biopsy to identify candidates for avoidance of surgery following neoadjuvant chemotherapy for breast cancer

Purpose@#This study aimed to evaluate the role of Doppler ultrasound (US) and elastography to identify residual breast cancer for patients showing near complete response following chemotherapy on magnetic resonance imaging (MRI). @*Methods@#Between September 2016 and January 2018, 40 breast cancer patients who showed near complete response (either tumor size ≤0.5 cm or lesion-to-background parenchymal signal enhancement ratio ≤1.6) on MRI following neoadjuvant chemotherapy were prospectively enrolled. After excluding seven women who did not undergo Doppler US and elastography, 33 women (median age, 49 years; range, 32 to 67 years) were analyzed. On the day of surgery, women underwent Doppler US and elastography for tumor bed prior to US-guided core needle biopsy. Histopathologic results of biopsy and surgery were evaluated. Negative predictive value (NPV) and false negative rate (FNR) of biopsy and the combined Doppler US and elastography were analyzed, respectively. @*Results@#After surgery, nine women had residual cancers and 24 women had pathologic complete response. The NPV and FNR of biopsy were 92% (24 of 26) and 22% (2 of 9), respectively. The NPV and FNR of combined Doppler US and elastography were 100% (14 of 14) and 0% (0 of 9), respectively. All of nine women with residual cancers had positive vascularity or elasticity. Two women with false-negative biopsy results, having 0.3 cm or 2.5 cm ductal carcinoma in situ at surgery, showed positive vascularity or elasticity. @*Conclusion@#Tumor bed showing positive vascularity or elasticity indicates residual breast cancer for patients showing near complete response on MRI following chemotherapy.

Diagnosis of Infectious Spondylitis Using Non-Contrast Enhanced MRI With Axial Diffusion-Weighted Images: Comparison With Gadolinium-Enhanced MRI

Purpose@#To assess the diagnostic performances of diffusion-weighted imaging (DWI)-included non-contrast magnetic resonance imaging (MRI) compared to standard contrastenhanced MRI for infectious spondylitis. @*Materials and Methods@#This study involved 154 participants: a spondylitis group (n = 76) and a control group (n = 78) with Modic type 1 degeneration or recent compression fractures. Two readers independently reviewed paraspinal soft tissue signal change and abscess with 5-scale confidence scores based on two image sets: one featuring both non-contrast-enhanced MRI (NCEI) and DWI and the other consisting of NCEI and contrast-enhanced fat-suppressed T1-weighted imaging (CEFST1). The diagnostic performance of the two image sets was compared using McNemar tests for sensitivity, specificity, and area under the receiver operating characteristics (AUROC) analysis. Interobserver agreements (κ) for each images sets were also calculated. @*Results@#The sensitivity and specificity for infectious spondylitis were 90.8% and 69.2% for NCEI + DWI, 96.1% and 60.3% for NCEI + CEFST1 in reader 1, whereas it was 92.1% and 66.7% for NCEI + DWI, and 96.1% and 68.0% for NCEI + CEFST1 in reader 2. Sensitivities and specificities were not significantly different between NCEI + DWI and NCEI + CEFST1 (reader 1: p = 0.289, 0.065; reader 2: p = 0.250, > 0.999, respectively). However, the AUROC was not considerably different between the two modalities in only one reader (p = 0.306 in reader 1, p = 0.031 in reader 2). Interobserver agreement for infectious spondylitis was moderate (κ = 0.55) in NCEI + DWI and substantial (κ = 0.66) in NCEI + CEFST1. @*Conclusion@#Non-contrast enhanced MRI with additional DWI is as effective for diagnosing infectious spondylitis as a contrast-enhanced MRI.

The Fracture Risk Assessment Tool Probability and Trabecular Bone Score Mediate the Relationship between Sphingosine 1-phosphate Levels and Fracture Risk

Background@#The sphingosine 1-phosphate (S1P) concentration is a potential biomarker of osteoporotic fracture and is associated with both the fracture risk assessment tool (FRAX) probability and trabecular bone score (TBS), which are well-known predictors of fracture. We sought to estimate the effect of the S1P concentration on fracture risk using the FRAX probability and TBS as mediators. @*Methods@#Plasma S1P concentrations, FRAX variables, and TBSs were measured in 66 postmenopausal women with fractures and 273 postmenopausal women without fractures. Associations between S1P concentration, FRAX probability, TBS, and fracture risk were analyzed using correlation, logistic regression, and mediation analyses. @*Results@#Subjects in the highest S1P concentration tertile had a higher fracture risk (odds ratio [OR], 5.09; 95% confidence interval [CI], 2.22–11.67) than those in the lowest S1P concentration tertile before adjustment. Subjects in the highest FRAX probability tertile had a higher fracture risk (OR, 14.59; 95% CI, 5.01–42.53) than those in the lowest FRAX probability tertile before adjustment. Subjects in the lowest TBS tertile had a higher fracture risk (OR, 4.76; 95% CI, 2.28–9.93) than those in the highest TBS tertile before adjustment. After adjustment for FRAX probability and TBS, the highest S1P concentration tertile was still associated with a higher fracture risk (OR, 3.13; 95% CI, 1.28–7.66). The FRAX probability and TBS accounted for 32.6% and 21.7%, respectively, of the relationship between the S1P concentration and fracture risk. @*Conclusions@#The relationship between the circulating S1P concentration and fracture risk was partly mediated by the FRAX probability, bone microarchitecture, and other factors.