Chungnam National University Hospital Research Articles

Relationship between Permanent Catheter Patency and Nutrient Score in Patients Aged >75 Years Requiring Renal Replacement Therapy.

Background: Malnutrition is common in patients undergoing hemodialysis and is a powerful predictor of morbidity and mortality. This study aimed to investigate the effect of nutritional status on permanent catheter patency in elderly patients aged >75 years of age undergoing dialysis using tunneled dialysis catheters; Methods: Records of 383 patients whose nutritional factors and body cell mass (BCM) were measured simultaneously at the start of dialysis between 14 January 2020 and 30 September 2023, at Chungnam National University Hospital, were retrospectively reviewed. The relationships between permanent catheter patency at 180 days and BCM parameters and clinical parameters were studied using Kaplan-Meier survival curves and multivariate Cox proportional hazards analysis. Results: Age and sexual differences were significant (p ≤ 0.05), and most of the BCM parameters and BCM were not significant (p ≤ 0.05), except for intracellular water. Permanent catheter patency was superior at low controlling nutritional status (CONUT) scores (p < 0.05). After adjustment for covariates, the CONUT score remained an independent factor associated with permanent catheter-patency survival; Conclusions: CONUT scores measured before the start of dialysis are expected to play an important role in predicting the prognosis of permanent catheter-patency survival in patients aged >75 years.

Prediction of lung cancer using novel biomarkers based on microbiome profiling of bronchoalveolar lavage fluid

There is an unmet need for biomarkers for the diagnosis of lung cancer and decision criteria for lung biopsy. We comparatively investigated the lung microbiomes of patients with lung cancer and benign lung diseases. Patients who underwent bronchoscopy at Chungnam National University Hospital between June 2021 and June 2022 were enrolled. Bronchoalveolar lavage fluid (BALF) was collected from 24 patients each with lung cancer and benign lung diseases. The samples were analyzed using 16S rRNA-based metagenomic sequencing. We found that alpha diversity and the beta diversity distribution (P = 0.001) differed significantly between patients with benign lung diseases and those with lung cancer. Firmicutes was the most abundant phylum in patients with lung cancer (33.39% ± 17.439), whereas Bacteroidota was the most abundant phylum in patients with benign lung disease (31.132% ± 22.505), respectively. In differential abundance analysis, the most differentially abundant microbiota taxon was unclassified_SAR202_clade, belonging to the phylum Chloroflexi. The established prediction model distinguished patients with benign lung disease from those with lung cancer with a high accuracy (micro area under the curve [AUC] = 0.98 and macro AUC = 0.99). The BALF microbiome may be a novel biomarker for the detection of lung cancer.

Quantitative Computed Tomography Lung COVID Scores with Laboratory Markers: Utilization to Predict Rapid Progression and Monitor Longitudinal Changes in Patients with Coronavirus 2019 (COVID-19) Pneumonia.

Coronavirus disease 2019 (COVID-19), is an ongoing issue in certain populations, presenting rapidly worsening pneumonia and persistent symptoms. This study aimed to test the predictability of rapid progression using radiographic scores and laboratory markers and present longitudinal changes. This retrospective study included 218 COVID-19 pneumonia patients admitted at the Chungnam National University Hospital. Rapid progression was defined as respiratory failure requiring mechanical ventilation within one week of hospitalization. Quantitative COVID (QCOVID) scores were derived from high-resolution computed tomography (CT) analyses: (1) ground glass opacity (QGGO), (2) mixed diseases (QMD), and (3) consolidation (QCON), and the sum, quantitative total lung diseases (QTLD). Laboratory data, including inflammatory markers, were obtained from electronic medical records. Rapid progression was observed in 9.6% of patients. All QCOVID scores predicted rapid progression, with QMD showing the best predictability (AUC = 0.813). In multivariate analyses, the QMD score and interleukin(IL)-6 level were important predictors for rapid progression (AUC = 0.864). With >2 months follow-up CT, remained lung lesions were observed in 21 subjects, even after several weeks of negative reverse transcription polymerase chain reaction test. AI-driven quantitative CT scores in conjugation with laboratory markers can be useful in predicting the rapid progression and monitoring of COVID-19.

Diagnostic Value of Transbronchial Lung Cryobiopsy Using an Ultrathin Cryoprobe and Guide Sheath for Peripheral Pulmonary Lesions.

The addition of cryobiopsy to conventional biopsy methods improves the diagnostic yield of peripheral pulmonary lesions. Moreover, cryobiopsy with a guide sheath (GS) provides additional diagnostic benefits. Semi-real-time biopsy can be repeatedly performed using conventional biopsy devices and a GS, and subsequent cryobiopsy can be easily performed at the same location. Recently, a disposable 1.1mm-diameter ultrathin cryoprobe has been developed and can be used with a 1.95mm GS in a 2.0mm working channel. In this study, we evaluated the diagnostic performance of transbronchial lung cryobiopsy (TBLC) with the 1.1mm cryoprobe and a GS in patients with peripheral pulmonary lesions. We retrospectively reviewed the medical records of patients who underwent endobronchial ultrasound transbronchial lung biopsy with a guide sheath and TBLC from July 23, 2021 to April 30, 2022 at Chungnam National University Hospital. Of a consecutive series of 229 patients, 199 were included. The diagnostic yields of forceps biopsy and cryobiopsy were 65.3% (130/199) and 84.4% (168/199), respectively, and the total diagnostic yield was 91.5% (182/199) ( P <0.001 vs. forceps biopsy). Multivariate analysis showed that solid lesion morphology [adjusted odds ratio (OR) 3.659, P =0.002] was associated with a significantly greater diagnostic yield of cryobiopsy, whereas a lesion diameter >20mm ( P =0.026; adjusted OR 3.816) and 'within' orientation ( P =0.004; adjusted OR 6.174) were associated with a significantly greater overall diagnostic yield. TBLC using an ultrathin cryoprobe and GS markedly improves the diagnostic yield.

An Assessment of Marrow-Infiltrating T Cells in Early Relapsed Hematologic Cancer Patients Post Allogeneic Hematopoietic Stem Cell Transplantation

Background: Relapse is the major treatment failure of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. Especially, early relapse had seriously bad prognosis. And tumor-infiltrating T cells play an important role in disease progression and recurrence. However, there is lack of data about the marrow-infiltrating T cell of early relapsed patients compared to those with complete remission (CR) at an early timepoint after HSCT. Therefore, we analyzed the differentiation stage and expression of inhibitory receptors of the marrow-infiltrating T cell in the early stages of allogeneic HSCT. Method: A total of 40 samples from patients treated at Chungnam National University Hospital were collected between April 2021 and October 2022. We used flow cytometry to classify T cells into five subtypes using CD45RA, CD95, and CCR7: naïve, stem cell memory (SCM), central memory (CM), effector memory (EM) and effector memory with positive CD45RA (EMRA). Otherwise, we analyzed regulatory T cell (Treg) by defining as CD25 highCD127 low and divided them into three categories using CD25 and CD45RA: naïve, active and non-suppressive Treg. We defined early relapse (ER) as relapse within 6 months of allogeneic HSCT. High-throughput single-cell RNAseq assays from BM lymphocytes isolated by density gradients were performed to determine the expression and cell composition of previously irradiated markers. Results: With this approach, marrow-infiltrating T cells were analyzed in 40 patients (10 patients with early relapse) with a median age of 57 years (ranged from 30 to 71). AML is the most common disease at 60%, followed by MDS (20%), ALL (15%) and PMF (2.5%). Stem cell sources were 32.5% from matched sibling donor, 37.5% from haplo-identical donor and 27.5% from matched unrelated donor. All patients received mobilized peripheral blood stem cell transplantation. Marrow-infiltrating CD3+T cell counts were lower in patients with allogeneic HSCT compared to normal subjects (CD3+T cells: 13.89% in HSCT patient and 9.116% in ER patients vs. 34.19% in normal subjects, p&amp;lt; 0.0001). In addition, CD3+CD8+T cells were higher in CR than ER patients (CD3+CD8+T cells: 50.39% in CR vs. 30.41% in ER patients, p&amp;lt; 0.0033). In HSCT patients, naïve was higher, and EM and EMRA were lower than those in normal subjects among CD4+T cells (naïve; 8.629% in ER patients and 5.119% in CR patient's vs 45.76% in normal subjects, p&amp;lt; 0.0001/EM; 54.04% in ER patients and 55.93% in CR patients vs 18.61 in normal subject, p= 0.0003 and p&amp;lt; 0.0001 respectively). Of CD3+T cells, the proportion and expression level of TIM-3 was higher ER patients than in CR patients (56.33% in ER patients vs 39.20% in CR patients, p= 0.0185/MFI; 1873 in ER patients vs. 826.7 in CR patients, p= 0.0331). Of CD4+T cells, the percentage of TIM-3 was lower in normal subjects than in allogeneic HSCT patients (7.794% in normal vs 30.11% in CR patients and 26.04% in ER patients, p= 0.0002 and p= 0.0102 respectively). In patients with ER, naïve and EM was higher than those in CR patients among CD8+T cells (naïve; 8.680% in ER patients vs 4.066% in CR patients, p= 0.4001 /EM; 54.44% in ER patients vs 44.33% in CR patients, p= 0.3039). Of CD8+ EMRA T cell, the expression of TIM-3 was higher in ER patients than in CR patients (MFI; 1441 in HSCT patients vs 421.7 in normal, p=0.1038). Otherwise, of CD3+CD4-CD8-, The percentage of TIM3 was higher in ER patients than CR patients (80.33 % in ER patients vs 62.49% in CR patients, p= 0.0333). Treg levels were no significant difference between CR and ER. We have obtained single-cell sequencing data from two CR (complete response) patients and two ER (early relapse) patients, representing each group. Since the classified groups exhibited ambiguous phenotypes, they were reclassified based on specific markers of cell groups. The reclassified groups showed a higher proportion of HCS (Hematopoietic Stem Cell)-like cells in relapsed patients (+10.14%, P=0.368) and a lower proportion of CD8+ T cells (-13.40%, p=0.068). The HSC-like cells in relapsed patients exhibited higher expression of TIM3 ligand than in CR patients Conclusion: Among the IRs, TIM3 had the highest expression of all cell groups (CD4 T cells, CD8 T cells and Treg) compared with other IRs at the early stage of allogeneic HSCT. So, TIM3 might be a potential target for preventing relapse in hematologic cancer patients after allogeneic HSCT in the future.

Clinical factors for choosing active surveillance: an analysis of papillary thyroid microcarcinoma patients with recurrence.

Active surveillance (AS) has been suggested as a management option for low-risk papillary thyroid microcarcinoma (PTMC). However, the currently proposed selection criteria for AS application do not consider various clinical factors. The purpose of this study was to analyze clinical factors related to recurrence that could be confirmed preoperatively in patients who underwent surgery for PTMC and to identify factors worth considering when deciding whether to apply AS. Data were collected from patients with PTMC who underwent surgical treatment at Chungnam National University Hospital. A retrospective cohort was established according to the presence or absence of recurrence during the follow-up period. In total, 2717 patients were enrolled, of whom 60 experienced recurrence. Various clinical factors that could be identified before surgery were analyzed. The relationship between various clinical factors that could be confirmed preoperatively and recurrence was confirmed through Cox regression analysis and Kaplan-Meier curve analysis. BRAF mutation and the tall cell variant were significantly more common in patients with recurrence. In patients aged 55 years or older, the risk of recurrence was lower than in younger patients, while the recurrence-free survival (RFS) rate was higher. When choosing between surgical treatment or AS in PTMC patients, additional consideration of the patient's clinical factors, such as age and BRAF mutation status, may be required in addition to the existing criteria.

Abdominal aortic calcification in patients newly diagnosed with essential thrombocythemia.

Although atherosclerosis is likely to be involved in the development of arterial thrombotic events in patients with essential thrombocythemia (ET), abdominal aortic calcification (AAC) has rarely been investigated. We evaluated the prevalence and clinical relevance of AAC at the time of ET diagnosis. This retrospective study included patients newly diagnosed with ET who underwent abdominal computed tomography (CT) at the time of diagnosis between January 2002 and December 2021 at Chungnam National University Hospital, Daejeon, Korea. CT images were reviewed and an aortic calcification score was assigned. Of the 94 patients (median age, 62 yr; range, 18‒90 yr), AAC was detected in 62 (66.0%). AAC was most commonly mild (33.0%), followed by moderate (22.7%) and severe (5.3%). Old age [odds ratio (OR), 34.37; 95% confidence interval (CI), 12.32‒95.91; P＜0.001] was an independent risk factor for AAC. The patients with AAC had a higher WBC count (11.8±4.7 vs. 9.7±2.9×109/L, P=0.017), higher neutrophil-to-lymphocyte ratio (4.3±2.7 vs. 3.1±1.5, P=0.039), and higher JAK2V617F positivity (81.5% vs. 58.8%, P=0.020) compared to those without AAC. AAC was an independent risk factor for arterial thrombotic vascular events that occurred before or at diagnosis of ET (OR, 4.12; 95% CI, 1.11‒15.85; P=0.034). AAC is common in patients with ET and is associated with arterial thrombotic events.

Smartphone-Based LiDAR Application for Easy and Accurate Wound Size Measurement.

The accurate assessment of wound size is a critical step in advanced wound care management. This study aims to introduce and validate a Light Detection and Ranging (LiDAR) technique for measuring wound size. Twenty-eight wounds treated from December 2022 to April 2023 at the Chungnam National University Hospital were analyzed. All the wounds were measured using three techniques: conventional ruler methods, the LiDAR technique, and ImageJ analysis. Correlation analysis, linear regression, and Bland-Altman plot analysis were performed to validate the accuracy of the novel method. The measurement results (mean ± standard deviation) obtained using the ruler method, LiDAR technique, and ImageJ analysis were 112.99 ± 110.07 cm2, 73.59 ± 72.97 cm2, and 74.29 ± 72.15 cm2, respectively. The Pearson correlation coefficient was higher for the LiDAR application (0.995) than for the conventional ruler methods (mean difference, -5.0000 cm2), as was the degree of agreement (mean difference, 38.6933 cm2). Wound size measurement using LiDAR is a simple and reliable method that will enable practitioners to conveniently assess wounds with a flattened and irregular shape with higher accuracy. However, non-flattened wounds cannot be assessed owing to the technical limitations of LiDAR.

Autoimmune Limbic Encephalitis in Patients with Hematologic Malignancies after Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide.

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with post-transplant cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflammatory biomarkers, and reconstitution of various T cell populations. Of 35 patients, 4 developed LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.

#4979 MORTALITY AND BIOIMPEDANCE SPECTROSCOPY–BASED DRY WEIGHT MEASUREMENT ERROR IN ELDERLY PATIENTS UNDERGOING HEMODIALYSIS

Abstract Background and Aims Dry weight (DW) estimation is important for patients undergoing hemodialysis. Although bioimpedance spectroscopy (BIS) is often employed to evaluate DW, BIS-based DW frequently differs from clinical DW. In this study, the characteristics of elderly patients were evaluated by separating them into groups based on the degree of disparity between the BIS-based DW and the clinically appropriate (DWGAP), and the mortality of each group was compared. Method This retrospective study included patients who underwent hemodialysis at Chungnam National University Hospital from January 1, 2016, to June 2020. All patients were aged ≥60 years. Patients with cancer, recipients of kidney transplant, and patients who dropped out of the study within 3 years were excluded. Body composition was assessed using a portable BIS device (Fresenius Medical Care, Bad Homburg, Germany). The BIS dataset includes extracellular water (ECW), intracellular water (ICW), and total body water level (TBW) as well as the lean tissue index (LTI), fat mass index (FTI), ECW/ICW ratio (E/I), lean tissue mass, fat mass (FAT), adipose tissue mass (ATM), and body cell mass (BCM). The absolute value of the gap between the BIS-based DW and the actual clinically appropriate dry weight was determined (DWGAP). To assess differences in blood chemistry and survival rate, four groups were classified based on the absolute value of DWGAP; Group 1: DWGAP &amp;lt; 0.5 kg, Group 2: 0.5 kg ≤ DWGAP &amp;lt; 1 kg, Group 3: 1 kg ≤ DWGAP &amp;lt; 2 kg, and Group 4: 2 kg &amp;lt; DWGAP. The mortality data of patients up to 3 years after BIS measurement were collected. Results There were 1024 patients in all. The study excluded 29 individuals with cancer, 31 patients with KT, and 249 participants with a loss of follow-up before 36 months. A total of 715 patients were analyzed: Group 1 (n = 236), Group 2 (n = 171), Group 3 (n = 137), and Group 4 (n = 171). The mean age for each group was 71.97, 70.73, 71.58, and 70.4 years, respectively. Groups 1 and 2 had the same survival rates (78%); however, Group 3 had a lower rate (73%) and Group 4 showed a significant decline (59%). In the laboratory test, Group 4 had lower hemoglobin, total protein, albumin, creatinine, and chloride levels than Groups 1, 2, and 3. In the BIS data, ECW and E/I were higher in Group 4 than in Groups 1, 2, and 3. Conclusion In the elderly patient group, mortality increased in the group where the DWGAP was &amp;gt;2 kg. Lower blood albumin levels, total protein levels, and E/I ratios of ≥1 were detected in the group with a gap of ≥2 kg, and these parameters are likely to adversely affect the survival of elderly patients requiring dialysis.

Mitochondrial Ribosomal Protein L14 Promotes Cell Growth and Invasion by Modulating Reactive Oxygen Species in Thyroid Cancer.

The mitochondrial ribosomal protein L14 (MRPL14) is encoded by a nuclear gene and participates in mitochondrial protein translation. In this study, we aimed to investigate the role of MRPL14 in thyroid cancer. We investigated the association between MRPL14 expression and clinicopathological features using The Cancer Genome Atlas (TCGA) and Chungnam National University Hospital (CNUH) databases. Functional studies of MRPL14, including proliferation, migration, invasion, mitochondrial oxidative phosphorylation and reactive oxygen species (ROS) production, were performed in papillary thyroid cancer (PTC) cell lines (B-CPAP and KTC-1). Based on the TCGA dataset, PTC tissues lost mitochondrial integrity and showed dysregulated expression of overall mitoribosomal proteins (MRPs) compared with normal thyroid tissues. Of 78 MRPs, MRPL14 was highly expressed in thyroid cancer tissues. MRPL14 overexpression was significantly associated with advanced tumor stage, extrathyroidal extension, and lymph node metastasis. MRPL14 increased cell proliferation of thyroid cancer and promoted cell migration via epithelial-mesenchymal transition-related proteins. Moreover, MRPL14 knockdown reduced the expression of oxidative phosphorylation complex IV (MTCO1) and increased the accumulation of ROS. Cotreatment with a ROS scavenger restored cell proliferation and migration, which had been reduced by MRPL14 knockdown, implying that ROS functions as a key regulator of the oncogenic effects of MRPL14 in thyroid cancer cells. Our findings indicate that MRPL14 may promote cell growth, migration, and invasion by modulating ROS in thyroid cancer cells.

A circulating microRNA panel as a novel dynamic monitor for oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) has high recurrence and mortality rates despite advances in diagnosis and treatment. Therefore, it is necessary to identify new biomarkers for early detection, efficient monitoring, and prognosis prediction. Since microRNA (miRNA) is stable and detectable in serum, it has been reported to inform the diagnosis and monitor disease progression through liquid biopsy. In this study, a circulating specific miRNA panel in OSCC patients was developed, and its usefulness as a dynamic monitor was validated. Small RNAs were extracted from the serum of OSCC patients (n = 4) and normal controls (n = 6) and profiled using next-generation sequencing. NGS identified 42 differentially expressed miRNAs (DEmiRNAs) in serum between patients with OSCC and healthy controls, with threefold differences (p < 0.05). Combining the 42 DEmiRNAs and The Cancer Genome Atlas (TCGA) databases OSCC cohort, 9 overlapping DEmiRNAs were screened out. Finally, 4 significantly up-regulated miRNAs (miR-92a-3p, miR-92b-3p, miR-320c and miR-629-5p) were identified from OSCC patients via validation in the Chungnam National University Hospital cohort. Application of the specific miRNA panel for distinguishing OSCC patients from healthy controls produced specificity and sensitivity of 97.8 and 74%, respectively. In addition, the serum levels of these 4 miRNAs significantly decreased after complete surgical resection and increased after recurrence. We suggest that circulating 4-miRNA panel might be promising non-invasive predictors for diagnosing and monitoring the progression of patients with OSCC.

Ultrasound Renal Score to Predict the Renal Disease Prognosis in Patients with Diabetic Kidney Disease: An Investigative Study.

Renal disease associated with type 2 diabetes mellitus (T2DM) has become the leading cause of chronic kidney disease (CKD). Renal ultrasonography is an imaging examination required in the work-up of renal disease. This study aimed to identify the differences in renal ultrasonographic findings between patients with and without DM, and to evaluate the relationship between renal ultrasound findings and renal prognosis in patients with DM. A total of 252 patients who underwent renal ultrasonography at Chungnam National University Hospital were included. Kidney disease progression was defined as a ≥10% decline in the annual estimated glomerular filtration rate (eGFR), which, in this paper, is referred to as ΔeGFR/year, or the initiation of renal replacement therapy after follow-up. The renal scoring system was evaluated by summing up the following items: the value of renal parenchymal echogenicity (0: normal; 1: mildly increased; and 2: increased) and the shape of the cortical margin (0: normal and 1: irregular; right kidney length/height (RH-0 or 1), mean cortical thickness/renal length/height (CKH-0 or 1), and cortical thickness/parenchymal thickness (CK/PK-0 or 1) based on the median: 0-above median, and 1-below median). Patients with DM had thicker renal PKH than those without, despite having lower eGFRs (0.91 ± 0.15, 0.86 ± 0.14, p = 0.006). In the progression group, the renal scores were significantly higher than those from the non-progression group. In the multivariate logistic regression analysis, the higher renal scores, presence of DM, and younger age were independently predicted for renal disease progression after adjusting for confounding variables, such as the presence of hypertension, serum hemoglobin and albumin levels, and UPCR. In conclusion, patients with high renal scores were significantly associated with renal disease progression. Our results suggest that renal ultrasonography at the time of diagnosis provides useful prognostic information in patients with kidney disease.

Association of ultra-early diffusion-weighted magnetic resonance imaging with neurological outcomes after out-of-hospital cardiac arrest

BackgroundThis study aimed to investigate the association between ultra-early (within 6 h after return of spontaneous circulation [ROSC]) brain diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological outcomes in comatose survivors after out-of-hospital cardiac arrest.MethodsWe conducted a registry-based observational study from May 2018 to February 2022 at a Chungnam national university hospital in Daejeon, Korea. Presence of high-signal intensity (HSI) (PHSI) was defined as a HSI on DW-MRI with corresponding hypoattenuation on the apparent diffusion coefficient map irrespective of volume after hypoxic ischemic brain injury; absence of HSI was defined as AHSI. The primary outcome was the dichotomized cerebral performance category (CPC) at 6 months, defined as good (CPC 1–2) or poor (CPC 3–5).ResultsOf the 110 patients (30 women [27.3%]; median (interquartile range [IQR]) age, 58 [38–69] years), 48 (43.6%) had a good neurological outcome, time from ROSC to MRI scan was 2.8 h (IQR 2.0–4.0 h), and the PHSI on DW-MRI was observed in 46 (41.8%) patients. No patients in the PHSI group had a good neurological outcome compared with 48 (75%) patients in the AHSI group. In the AHSI group, cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels were significantly lower in the group with good neurological outcome compared to the group with poor neurological outcome (20.1 [14.4–30.7] ng/mL vs. 84.3 [32.4–167.0] ng/mL, P < 0.001). The area under the curve for PHSI on DW-MRI was 0.87 (95% confidence interval [CI] 0.80–0.93), and the specificity and sensitivity for predicting a poor neurological outcome were 100% (95% CI 91.2%–100%) and 74.2% (95% CI 62.0–83.5%), respectively. A higher sensitivity was observed when CSF NSE levels were combined (88.7% [95% CI 77.1–95.1%]; 100% specificity).ConclusionsIn this cohort study, PHSI findings on ultra-early DW-MRI were associated with poor neurological outcomes 6 months following the cardiac arrest. The combined CSF NSE levels showed higher sensitivity at 100% specificity than on DW-MRI alone. Prospective multicenter studies are required to confirm these results.

Splenic Infarction in Patients with Philadelphia-negative Myeloproliferative Neoplasms.

Objective We retrospectively analyzed the prevalence and clinical features of splenic infarctions in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPNs). Patients Patients diagnosed with essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic/early primary myelofibrosis (pre-PMF), or PMF from January 1996 to October 2020 in Chungnam National University Hospital, Daejeon, Korea, were reviewed. Results A total of 347 patients (143 ET, 129 PV, 44 pre-PMF, and 31 PMF patients; 201 men and 146 women) with a median age of 64 (range 15-91) years old were followed up for a median of 4.7 (range 0.1-26.5) years. Fifteen (4.3%) patients exhibited splenic infarctions at the diagnosis. These were most common in PMF patients (12.9%), followed by pre-PMF (9.1%) and PV (5.4%) patients. Multifocal infarcts (60.0%) were most common, followed by solitary (33.3%) and extensive infarcts (6.7%). The cumulative incidence of thrombosis in patients with splenic infarctions tended to be higher than in those lacking infarctions (10-year incidence 46.7% vs. 21.0% in PV; p=0.215; 33.3% vs. 17.9% in pre-PMF; p=0.473) patients, but statistical significance was lacking. Palpable splenomegaly (hazard ratio 14.89; 95% confidence interval 4.00-55.35; p<0.001) was the only independent risk factor for splenic infarction. During follow-up, 5 (1.4%) patients developed splenic infarctions. Conservative treatment adequately controlled the symptoms; no serious complications were noted in any patient. Conclusion Splenic infarctions occurred most frequently in patients with PMF; it was rare in patients with ET. The clinical courses were generally mild.

Spousal caregiver burden among patient with cognitive impairment: effects on nutrition and other lifestyle factors

AbstractBackgroundAmong old adults, caring for a spouse with cognitive decline is well‐known to be associated with significant risk to the caregiver`s health such as cardiovascular disease, depression and, especially, cognitive impairment. It is important to understand the caregiving‐related risk factors for caregiver`s cognitive decline. Therefore, in this study, we examined the impact of caregiver`s burden on the lifestyle factors (malnutrition, sleep, depression, and physical activity) influencing cognitive decline among SCGs, focusing on nutritional status which contribute to SCG’s cognitive decline.MethodFrom May 2020 to May 2021, clinical evaluation and blood tests were conducted for patients who visited Chungnam National University Hospital Geriatric Neuropsychiatric Clinic with their spouse. A total of 51 subjects were included in the analysis. As clinical assessment, we evaluated the care burden (Zait burden interview), depression(Geriatric‐Depression‐Scale), sleep quality (Pittsburgh‐Sleep‐Quality‐Index), cognitive function(Mini‐Mental‐state‐exmination) physical activity(International‐Physical‐Activity‐Questionnaire), and dietary habits (Mini‐Nutrional‐Assessment).ResultAs the care‐recipient’s cognitive function declined, the caregiver`s burden were increased (β = ‐0.66, p &lt; 0.001). In linear regression analysis adjusted for age and sex, the SCG`s burden was significantly associated with the worse dietary habits (β = ‐3.194, p = 0.003) and increased level of depressed mood (β = 0.525, p &lt; 0.001). The SCG`s burden showed a trend level association with sleep quality (β = 0.292, p = 0.050) but no significant relationship with physical activity (β = ‐0.053, p = 0.742). The results were unchanged after excluding care‐recipients with normal cognition (n = 7).ConclusionThis study provides substantial evidence that SCGs are at risk for depression and malnutrition, which can further affect cognitive decline. As such, these factors should be well assessed and monitored among SCGs for patient with cognitive impairment.

Immune-Mediated Limbic Encephalitis after Haplo-Identical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclosphosphamide

Background: Immune-mediated limbic encephalitis (iLE) is a rare, but devastating complication that can develop after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated the biologic characteristics and clinical outcomes of patients with ALE after haploidentical HSCT combined with post-transplant cyclophosphamide (PTCy). Methods: We retrospectively analyzed consecutive adult patients with hematological malignancies who underwent haploidentical HSCT with PTCy at Chungnam National University Hospital between June 2016 and May 2020. ALE was diagnosed by the typical finding of magnetic resonance imaging. We compared the characteristics of patients with and without ALE. Results: Of 35 patients, 4 (11.4%) patients had iLE. The median patient age was 54 years (range, 28-60 years; male : female ratio of 3:1). There were no differences in age, gender, body mass index, hematological disease, conditioning regimen according to iLE status. However, baseline interleukin-6 level before conditioning chemotherapy was higher in patients with iLE than those without iLE [median (range), IL-6; 161.16(103.4 - 199.1) pg/mL vs. 33.78769( 2.1 - 59.1) pg/mL, p < 0.001]. And, Serum IL-6, interferon (IFN)-γ and tumor-necrosis factor (TNF)-α level on day 3 after HSCT was significantly higher in patients with iLE [median (range), IL-6; 355.8 (305.8 - 399.6) pg/mL vs. 63.47 (6.5 - 127.2) pg/mL, p < 0.001/ IFN-γ; 15.045 (6.342 - 29.341) pg/mL vs. 1.602 (0 - 4.036) pg/mL, p = 0.0093 / TNF-α; ; 21.019 (13.268 - 34.138) pg/mL vs. 7.637 (0 - 13.938) pg/mL, p = 0.0205 ]. Patients with iLE had a higher incidence of veno-occlusive disease (VOD) [2 of 4 (50%) vs. 3 of 31 (9.7%), p = 0.030]. The population of naïve regulatory T cells were higher in iLE patient group on day 3 after HSCT than non-iLE group. Overall survival was significantly shorter in patients with iLE [median, 1.5 months, 95% CI, 1.45 - 2.05 vs. 11.0 months, 95% CI, 8.2 - 13.7, p = 0.001]. Conclusion: Patients with high serum interleukin-6 level on baseline & post-transplant day 3, who underwent haploidentical HSCT with PTCy need to be aware of developing iLE.

Efficacy and safety of EXOWALK® on electromechanical-assisted gait training: study protocol for randomized controlled trial

BackgroundHigh-intensity repetitive task-specific practice might be the most effective strategy to promote motor recovery after stroke, and electromechanical-assisted gait training represents one of the treatment options. However, there is still difficulty in clarifying the difference between conventional gait training and electromechanically assisted gait training.MethodsThe study is a multicenter, randomized, parallel-group clinical trial for stroke patients. Three clinical research centers in Korea (Dongguk University Ilsan Hospital, Chungnam National University Hospital, and Seoul National University Bundang Hospital) will participate in the clinical trial and 144 stroke patients will be registered. Enrolled patients are assigned to two groups, an experimental group and a control group, according to a randomization table. In addition, patients are treated for half an hour (one session) five times a week for 4 weeks. Both groups carry out basic rehabilitation (central nervous system development therapy and strength exercise) and the experimental group executes robotic walking rehabilitation treatment, and the control group executes conventional gait rehabilitation treatment. The primary endpoint variable is the Functional Ambulation Category (FAC) that determines the degree of independent walking and is measured before, after, and after 4 weeks of treatment. Secondary endpoint variables are 11 variables that take into account motor function and range, measured at the same time as the primary endpoint variable.DiscussionThere are still insufficient data on the effectiveness of electromechanical-assisted gait training for stroke patients and large-scale research is lacking. Thus, the research described here is a large-scale study of stroke patients that can supplement the limitations mentioned in other previous studies. In addition, the clinical studies described here include physical epidemiological analysis parameters that can determine walking ability. The results of this study can lead to prove the generalizable effectiveness and safety of electromechanical-assisted gait training with EXOWALK®.Trial registrationClinical Research Information Service (CRIS), Republic of Korea KCT0003411, Registered on 30 October 2018

The rest period between chemotherapy and immunotherapy influences the efficacy of immune checkpoint inhibitors in lung cancer.

BackgroundThe use of immune checkpoint inhibitors (ICIs) as first‐line treatment rather than as second‐line treatment makes a big difference in the drug efficacy and progression‐free survival. However, the mechanism for this is still not clear. This study aimed to analyze the effects of the rest period between chemotherapy and immunotherapy on the efficacy of ICIs.MethodsThis study included 100 patients with advanced NSCLC treated with PD‐1/PD‐L1 inhibitors at Chungnam National University Hospital (CNUH) between May 2016 and August 2019. The rest period was defined from the last dose of cytotoxic chemotherapy to the first dose of ICIs. We retrospectively reviewed patients' clinical data and blood test records and analyzed lymphocyte subsets using flow cytometry.ResultsThe median rest period was 64 days. The long rest period group (≥36 days) showed significantly higher clinical benefits than the short rest period group (<36 days) (69.4% vs. 39.5%, p = 0.003). White blood cell (WBC) count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and neutrophil‐lymphocyte ratio (NLR) just before chemotherapy were not different between the two groups. However, the blood test after chemotherapy immediately before immunotherapy showed significantly higher ANC and NLR in the short rest period group than in the long rest period group. The frequency of the Th1 subset and PD‐1 + CD8+ T cells were significantly higher in the long rest period group than in the short rest period group.ConclusionTime interval from chemotherapy to immunotherapy may affect immune cell status and efficacy of ICIs.

P1036: VOLUMETRIC SPLENOMEGALY IN PATIENTS WITH POLYCYTHEMIA VERA

Background: At present, palpable splenomegaly is relatively uncommon in patients with polycythemia vera (PV), possibly because of early diagnosis facilitated by a lowering of the diagnostic thresholds for hemoglobin and hematocrit levels as well as the wide application of driver gene mutation tests. Radiological volumetric analysis of spleen size is now readily available. However, non-palpable splenomegaly in patients with PV has seldom been addressed. Aims: In this retrospective study, we evaluated non-palpable, volumetric splenomegaly defined based on age- and body surface area (BSA)–matched criteria in patients with PV diagnosed according to the 2016 World Health Organization diagnostic criteria. Methods: Patients with PV who underwent abdominal computed tomography (CT) and who had palpable splenomegaly at diagnosis from January 1991 to December 2020 at Chungnam National University Hospital were enrolled in the study. The spleen volume of each patient was determined by volumetric analysis of abdominal CT and adjusted for the patient’s age and BSA. And then the degree of splenomegaly was classified as follows: no splenomegaly, spleen volume less than the mean plus 2 SD of the reference volume based on both age and BSA; overt volumetric splenomegaly, spleen volume greater than the mean plus 3 SD of the reference volume based on both age and BSA; borderline volumetric splenomegaly, a spleen volume between no splenomegaly and overt splenomegaly; or palpable splenomegaly, spleen palpable below the left costal margin. Results: Of the 87 PV patients enrolled in the study, 15 (17.2%) had no splenomegaly, whereas 17 (19.5%), 45 (51.7%), and 10 (11.5%) had borderline volumetric, overt volumetric, and palpable splenomegaly, respectively. Spleen volume was significantly positively correlated with lactate dehydrogenase level (r = 0.227, P = 0.042) and tended to be positively related to white blood cell count (r = 0.209, P = 0.055) and monocyte count (r = 0.210, P = 0.059) at diagnosis. Spleen volume was not correlated with hemoglobin level, platelet count, or JAK2V617F burden at diagnosis. The degree of splenomegaly did not affect the cumulative incidence of thrombotic vascular events (10-year incidence: 7.7%, 0%, 22.3%, and 50.7%, respectively, P = 0.414). By contrast, splenomegaly tended to adversely affect myelofibrotic transformation (10-year cumulative incidence: 0%, 0%, 7.1%, and 30.3%, respectively, P = 0.062). Moreover, the cumulative incidence of myelofibrotic transformation was significantly higher in patients with overt volumetric or palpable splenomegaly than those with no or borderline volumetric splenomegaly (10-year incidence: 0% vs. 10.3%, respectively; 15-year incidence: 0% vs. 26.3%, respectively, P = 0.020). Overall survival (OS) differed among patients with different degrees of splenomegaly (15-year OS: 100%, 78.6%, 71.7%, and 51.9%, respectively, P = 0.021). The degree of splenomegaly was independent risk factor for both myelofibrotic transformation (hazard ratio [HR]: 7.75; 95% confidence interval [CI]: 1.87-21.10; P = 0.005) and OS (HR: 6.70; 95% CI: 1.89-23.72; P = 0.003). Summary/Conclusion: The degree of splenomegaly, including volumetric splenomegaly, based on age- and BSA-matched reference spleen volumes at diagnosis reflects disease progression in PV patients. Therefore, volumetric splenomegaly should be evaluated at the time of PV diagnosis and taken into consideration when predicting the prognosis of patients with this disorder.