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α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden
No full textIntroduction: Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains.
Methods: Using an α-synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo.
Results: No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α-synuclein seeding activity in CSF in vivo.
Discussion: Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF α-synuclein SAA has low sensitivity.
Highlights: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded α-synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT-QuIC does not detect α-synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala-predominant variants. LBP develops late in the disease course in ADAD. CSF α-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP
Possibility of improving TCR-T function through engineering method of directly combining 1G4 TCR and T cell co-stimulatory molecule ICD
No full textThis study proposes a novel approach to enhance the efficacy of adoptive T cell therapy (ACT), a form of immunotherapy for cancer treatment. Among ACT strategies, T cell receptor-engineered T (TCR-T) therapy can be applied to solid tumors by expressing TCRs on patient T cells to recognize tumor antigens and eradicate cancer cells. However, a significant challenge in ACT is the limited activation of T cells within the tumor microenvironment, leading to suppressed immune responses and reduced effectiveness. Therefore, we investigated methods to improve T cell function using the TCR-T system. Similar to techniques used in Chimeric Antigen Receptor T (CAR-T) therapies, we designed an engineering approach to directly link the intracellular domain (ICD) of co-stimulatory molecules to the TCR constant region. We aimed to assess the impact of this modification on T cell activation and anti-tumor effects. Using lentivirus-mediated gene delivery, we confirmed stable TCR expression levels in both cell lines and human primary cells. However, contrary to expectations, this modification did not enhance anti-tumor effects compared to conventional TCR in human primary cells; in some cases, these effects were diminished. Nevertheless, the engineering approach of directly linking the ICD of co-stimulatory molecules statistically significantly increased T cell activation levels compared to conventional TCR. These results resemble enhanced activation responses observed in CAR-T research, demonstrating the feasibility of a second-generation TCR-T system that successfully integrates signals 1 and 2. Therefore, the direct coupling of co-stimulatory molecule ICD to TCR via engineering provides a new strategy in TCR-T engineering to enhance ACT functionality, suggesting potential improvements in the field of immune oncology therapyMaste
Relapse in patients with antineutrophil cytoplasmic antibody-associated vasculitis undergoing dialysis: a single-centre retrospective study in South Korea
No full textObjectives: The disease activity of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) can decrease after dialysis, and relapse after dialysis is not well-studied. We investigated the clinical manifestations and factors associated with relapse in patients with AAV undergoing dialysis.
Methods: This retrospective study included data of patients with AAV undergoing dialysis due to renal involvement from July 2005 to March 2021 in a single tertiary centre in Seoul, Korea. Cox regression analysis was performed to identify relapse-associated factors.
Results: The study cohort included 38 patients with a median age of 64.0 years; 28 (73.7%) were female, and 35 (92.1%) patients were diagnosed with microscopic polyangiitis (MPA). At diagnosis, the mean Birmingham vasculitis activity score (BVAS) was 18.3 and 66.3% of the patients exhibited pulmonary manifestations. During follow-up, 12 patients experienced AAV relapse, including nine patients with diffuse alveolar haemorrhage (DAH), two patients with aggravated interstitial lung disease, and one patient with DAH accompanied with neuropathy. Clinical features including age, sex, and baseline BVAS did not significantly differ between the relapse and non-relapse groups. By univariable analysis, lung infiltration, DAH, corticosteroid pulse therapy for induction, and mean corticosteroid dose were significantly associated with relapse. Multivariable analysis revealed that DAH (adjusted hazard ratio 5.509, 95% CI 1.569-19.339; P=0.008) and mean corticosteroid dose (adjusted hazard ratio 1.381, 95% CI 1.161-1.642; P<0.001) were significantly associated with relapse.
Conclusions: In patients with AAV undergoing dialysis, DAH and mean corticosteroid dose were significantly associated with relapse, highlighting the importance of close monitoring
Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors
No full textPurpose: MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi.
Patients and methods: We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts for: pancreatic, gynecologic (GYN), non-small cell lung cancer (NSCLC), and other cancers harboring KRAS/NRAS mutations. Paired pretreatment and day 15 tumor biopsies and serial cell-free (cf)DNA were analyzed.
Results: A total of 91 patients initiated treatment, with 38 in dose escalation. Fifty-eight percent had ≥3 prior therapies. A total of 15 patients (17%) had colorectal cancer, 19 (11%) pancreatic, 15 (17%) NSCLC, and 32 (35%) GYN cancers. The recommended phase II dose (RP2D) was established as trametinib 2 mg daily days 1 to 14 and navitoclax 250 mg daily days 1 to 28 of each cycle. Most common adverse events included diarrhea, thrombocytopenia, increased AST/ALT, and acneiform rash. At RP2D, 8 of 49 (16%) evaluable patients achieved partial response (PR). Disease-specific differences in efficacy were noted. In patients with GYN at the RP2D, 7 of 21 (33%) achieved a PR and median duration of response 8.2 months. No PRs occurred in patients with colorectal cancer, NSCLC, or pancreatic cancer. MAPK pathway inhibition was observed in on-treatment tumor biopsies. Reductions in KRAS/NRAS mutation levels in cfDNA correlated with clinical benefit.
Conclusions: Navitoclax in combination with trametinib was tolerable. Durable clinical responses were observed in patients with RAS-mutant GYN cancers, warranting further evaluation in this population
Digital symbol-digit modalities test with modified flexible protocols in patients with CNS demyelinating diseases
No full textCognitive impairment (CI) is prevalent in central nervous system demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We developed a novel tablet-based modified digital Symbol Digit Modalities Test (MD-SDMT) with adjustable protocols that feature alternating symbol-digit combinations in each trial, lasting one or two minutes. We assessed 144 patients (99 with MS and 45 with NMOSD) using both MD-SDMT protocols and the traditional paper-based SDMT. We also gathered participants’ feedback through a questionnaire regarding their preferences and perceived reliability. The results showed strong correlations between MD-SDMT and paper-based SDMT scores (Pearsons correlation: 0.88 for 2 min; 0.85 for 1 min, both p < 0.001). Among the 120 respondents, the majority preferred the digitalized SDMT (55% for the 2 min, 39% for the 1 min) over the paper-based version (6%), with the 2 min MD-SDMT reported as the most reliable test. Notably, patients with NMOSD and older individuals exhibited a preference for the paper-based test, as compared to those with MS and younger patients. In summary, even with short test durations, the digitalized SDMT effectively evaluates cognitive function in MS and NMOSD patients, and is generally preferred over the paper-based method, although preferences may vary with patient characteristics
A study on image-to-image translation of MRI-to-FDG PET images between cognitively unimpaired individuals and Alzheimer’s patients using deep learning
No full textAlzheimer's disease is a subtype of dementia, representing a prevalent condition in an aging society. As of now, there is no cure for this condition, emphasizing the importance of early intervention to impede its progression. In the pursuit of proactive treatment at the initial stages, it is crucial to identify various biomarkers associated with Alzheimer's disease. Prior to MRI imaging, FDG PET stands out as a biomarker capable of early detection. Therefore, the objective of this study is to transform MRI images into FDG PET images. This research aims to transform paired images of MRI and FDG PET, among various biomarkers associated with Alzheimer's disease, with a particular focus on optimizing the generation of FDG PET images from MRI. To achieve this, image transformation experiments were conducted using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset, utilizing CycleGAN when the MRI and FDG PET images were captured within 180 days of each other. The quantitative metrics, including MAE, MSE, SSIM, and PSNR, indicate successful image generation compared to the baseline model. The MAE for the generated images versus the original images across all groups was consistently 0.011 ± 0.008, with AD, MCI, and CN recording values of 0.011 ± 0.007, 0.011 ± 0.008, and 0.011 ± 0.007, respectively. For MSE, the results were 0.002 ± 0.002 for all groups, with AD, MCI, and CN showing values of 0.002 ± 0.002 each. SSIM values were consistent across all groups at 0.987 ± 0.004, with AD at 0.987 ± 0.003, MCI at 0.986 ± 0.004, and CN at 0.988 ± 0.004. Notably, PSNR was 33.837 ± 3.951 across all groups, with values of 33.606 ± 3.929 for AD, 34.415 ± 4.044 for MCI, and 34.415 ± 4.044 for CN. These outcomes suggest that our study can generate images with features akin to FDG PET images, reflecting the functional aspects of the brain using MRI images. However, it is essential to acknowledge limitations, such as the inclusion of only cognitively intact individuals in the image generation experiment and the absence of qualitative assessments conducted by specialists. Nevertheless, despite these limitations, this study paves the way for future research, anticipating further exploration into the validity of transforming FDG PET images through MRI. Additionally, there is potential for research into the transformation of images related to the accumulation of amyloid. Furthermore, the application of this technique to neurodegenerative disorders detectable by FDG PET holds promising prospects.Maste
Effects of a Parent Education Program for Resilience on Parenting Stress and Self-Efficacy in Parents of Infants and Toddlers
No full textThis study aims to verify the effectiveness of a parent education program for resilience on the parenting stress and self-efficacy of parents of infants and toddlers based on Dr. Choi, Sung-Ae’s latest theory and practice on how to improve resilience developed by HeartMass Institute. This study would provide basic data for education, counseling, and treatment for parents of infants and toddlers, who complain of parenting stress and would increase their ability to flexibly cope with parenting stress and increase their self-efficacy, so that they can feel confident and regulate and control their behaviors.
For this purpose, 24 parents of infants and toddlers at E. Daycare Center in U. City were selected, 12 as an experimental group and 12 as a control group. A parent education program for resilience was conducted for a total of 6 sessions for 4 weeks for the 12 parents of infants and toddlers in the experimental group, and pre- and post-parenting stress and self-efficacy tests were conducted and analyzed using SPSS 25.0. An independent-samples t-test was conducted to verify the homogeneity of the two groups (experimental and control), and Kolmogorov-Smironov and Shapiro-Wilk tests were conducted to secure normality.
In addition, the mean and standard deviation of the pre- and post-test scores of the two groups (experimental and control) were calculated, and a paired-samples t-test was conducted to verify the difference between the pre- and post-test scores. To hear the voices of the participants, their post-program reflections were collected and analyzed. Conclusions are as follows.
First, parenting stress in the group of the parent education program for resilience decreased by 4.50 from the pre-test to the post-test, which was a statistically significant difference (t=2.67, *p<.05). In contrast, the control group showed little change in their scores. To look at the difference between the pre- and post-test scores of parental distress, a sub-factor of parenting stress, the experimental group showed a 3.33 decrease from pre- to post-test, which was a statistically significant difference (t=5.087, ***p<.001).
Second, self-efficacy in the group of the parent education program for resilience increased by 5.09 from the pre-test to the post-test, with a statistically significant difference (t=2.36, *p<.05). The control group decreased by 2.34 at the post-test, which was not statistically significant. Among the sub-factors of self-efficacy, confidence showed a statistically significant difference between the groups as it increased by 1.67 in the experimental group from the pre-test to the post-test (t=2.381, *p<.05).
Third, after the parent education program for resilience, this study analyzed the participants’ reflections with Google Word Cloud Generator and found that parents in the experimental group knew that there were other parents with similar minds to their own, and that the number of negative words decreased and changed to gratitude and appreciation through positivity and emotional control. In addition, they found their own strengths; their self-esteem increased; and their positivity increased through gratitude and fortune.
In conclusion, the effects of the parent education program for resilience on changes in parental distress and self-efficacy concerning parenting stress in parents of infants and toddlers are positive. Therefore, through the parent education program for resilience, parents can flexibly cope with parenting stress and increase their self-efficacy, which will increase their confidence and ability to regulate and control their behaviors.
Keywords: Resilience, Infant parents, Parent education program, Parenting stress, Self-efficacy|회복탄력성 부모교육 프로그램이 영유아기 부모의 양육스트레스와 자기효능감에 미치는 효과 아동·가정복지학 전공 김금남 지도교수 정민자 본 연구는 하트매스 연구소에서 개발하여 회복탄력성을 향상시키는 방법에 대한 최성애 박사의 최신 이론과 실습법을 근거로 ‘회복탄력성 부모교육 프로그램’을 실시하 여 영유아기 부모의 양육스트레스와 자기효능감에 미치는 효과를 검증해 보고자 한다. 이 를 통해 양육스트레스를 호소하는 영유아기 자녀를 둔 부모를 위한 교육, 상담과 치료를 위한 기초자료를 제공하고, 부모가 양육스트레스에 유연하게 대처하고 자기 효능감을 높여 자신감을 가지고, 자신의 행동을 조절, 통제할 수 있는 능력을 높이 고자 한다. 이를 위해 U시에 소재한 E어린이집 영유아 부모 24명 중 실험집단 12명, 통제집 단 12명으로 구성하였다. 실험집단 영유아 부모 12명을 대상으로 회복탄력성 부모 교육 프로그램을 4주 동안 총 6회기 실시하고, 사전·후 양육스트레스와 자기효능 감 검사를 실시하여 SPSS25.0을 이용하여 분석하였다. 두 집단(실험집단, 통제집단) 의 동질성을 검증하기 위하여 독립표본 t-검정(independent-samples t-test)와 정규 성을 확보하기 위해 Kolmogorov-Smironov, Shapiro-Wilk 검증을 실시하였다. 또한 두 집단(실험집단, 통제집단)의 사전, 사후검사 총점 평균과 표준편차를 산출 하였고, 사전, 사후검사 점수의 차이를 검증하기 위해 대응표본 t-검정 (Paired-samples t-test)을 실시하였다. 연구 참여자의 목소리를 듣고자 프로그램 이 후 소감문을 받아 분석하였다. 이를 통해 얻은 결론을 요약하면 다음과 같다. 첫째, 회복탄력성 부모교육 프로그램을 실시한 집단의 양육스트레스는 사전검사에 비해 사후검사에서 4.50이 낮아졌고, 통계적으로 유의미한 차이가 있었다.(t=2.67, *p<.05). 반면, 통제집단은 점수의 변화가 거의 일어나지 않았다. 양육스트레스의 하 위요인 중 부모의 고통은 집단별로 전후의 점수 차이를 살펴보면, 실험집단은 사전 검사에 비해 사후검사에서 3.33이 낮아졌고, 통계적으로 유의미한 차이가 있었다 (t=5.087, ***p<.001). 둘째, 회복탄력성 부모교육 프로그램을 실시한 집단의 자기효능감은 사전검사에 비해 사후검사에서 5.09 높아졌고, 통계적으로 유의미한 차이가 있었다(t=2.36, *p<.05). 통제집단은 사후검사에서 2.34가 낮아졌고, 통계적으로 유의미하지 않았다. 자기효능감의 하위요인 중 자신감은 집단별로 전후의 차이를 살펴보면, 실험집단은 사전검사에 비해 사후검사에서 1.67이 높아졌고, 통계적으로 유의미한 차이가 있었 다(t=2.381, *p<.05). 셋째, 회복탄력성 부모교육 프로그램 이후 소감문을 구글 워드 클라우드로 분석 한 결과 실험집단 부모들은 나와 비슷한 마음을 가진 부모들이 있다는 것을 알고, 긍정심과 감정조절을 통해 부정적인 말의 횟수는 줄어들고, 감사와 고마움의 마음 으로 변화됨을 알 수 있었다. 또한, 자신의 장점을 찾고 자존감이 올라갔으며 감사 와 다행으로 긍정심이 높아졌음을 알 수 있었다. 결론적으로 회복탄력성 부모교육 프로그램이 영유아기 부모의 양육스트레스의 부 모의 고통 변화와 자기효능감에 미치는 효과는 긍정적으로 볼 수 있다. 따라서 부 모는 회복탄력성 부모교육을 통해 양육스트레스에 유연하게 대처하고 자기효능감을 높여 자신감을 가지고, 자신의 행동을 조절, 통제할 수 있는 능력이 높아질 것이다. 주요어: 회복탄력성, 영유아기부모, 부모교육프로그램, 양육스트레스, 자기효능감Maste
Hydrogen Embrittlement Behavior in API X52 Steel for High-pressure Hydrogen Transportation
No full textPurpose: The purpose of this study is to understand hydrogen penetration, hydrogen-induced deformation, and fracture behavior in API X52 steel.
Method: Microstructural analysis of API X52 steel was conducted, followed by the slow strain rate test (SSRT) and the small punch test (SPT) in nitrogen and hydrogen atmospheres. The obtained results were evaluated to assess the susceptibility of the material to hydrogen embrittlement.
Results: The SSRT revealed predominantly ductile fractured surfaces in the nitrogen atmosphere specimen, whereas brittle fractured surfaces were observed at the edges. The specimen in the hydrogen atmosphere exhibited elongated dimples and some internal cracks in the central region. The SPT revealed circular cracks and dimples in the nitrogen atmosphere specimen. In contrast, hydrogen atmosphere specimens displayed fractures in the form of a mix of cleavage fractures, dimples, and internal, circumferential, and radial cracks.
Conclusion: Neither band structure nor MnS inclusions significantly influenced hydrogen embrittlement in API X52 steel. Brittle fractures were mainly observed at the grain boundaries of ferrite and pearlite, the primary microstructural constituent, or within ferrite grains
Prognostic Analysis of Cancer Patients with Septic Shock In Emergency Department from 2009 to 2017 : A Retrospective Cohort Study
No full textThe increasing incidence of cancer significantly strains global healthcare finances, particularly among individuals aged 75 and older, leading to more frequent emergency department (ED) visits and treatments for cancer patients. Despite advancements in cancer diagnosis and treatment, prolonged treatment and associated complications contribute to various organ dysfunctions, with septic shock being as a common life- threatening complication among cancer patients. Although recent studies show improved survival outcomes for cancer patients with septic shock, managing their ED care remains challenging due to extensive resource demands and costs. Neutropenia is prevalent among cancer patients with septic shock; however, its prognostic impact remains unclear. Furthermore, septic shock often leads to acute kidney injury (AKI), a complication associated with increased mortality rates and medical expenses in cancer patients. Our population-based study aims to assess trends in mortality rates among cancer patients experiencing septic shock, evaluate the impact of neutropenia, and explore factors associated with sepsis-related AKI to provide insights for improved treatment strategies. Method This population-based cohort study utilized data from the Korean National Health Information Database (NHID) spanning from 2009 to 2017. Patients presenting with septic shock through the emergency department were identified using clinical surveillance criteria. Cancer patients within this cohort were identified by diagnosis codes within 90 days before admission. Descriptive analyses assessed characteristics and mortality rates among survivors and non-survivors at 30 days and 1 year. Adjusted hazard ratios (HR) for 30-day mortality were calculated, controlling for age, sex, Charlson Comorbidity Index (CCI) and hospitalization year. Additional analyses explored neutropenia presence among cancer patients and its association with mortality rates. In another AKI cohort, baseline characteristics were compared between groups based on dialysis need for septic AKI and 2-year survival status. Independent predictors for septic AKI were identified through multivariate logistic regression analyses, and Cox-proportional hazards models compared survivors and non-survivors at 30 days and 2 years. All analyses used two-sided P values < 0.05 and were conducted using SAS Enterprise Guide version 7.1. Results From 2009 to 2017, 322,526 patients were admitted to South Korean EDs with septic shock, 43,850 (13.6%) had a cancer diagnosis within the preceding 90 days. After excluding patients under 18 years old or with incomplete data, 43,466 patients were analyzed, among whom 22,639 (52.1%) died within 30 days and 35,325 (81.3%) died within 1 year. From 2010 to 2015, there was a slight decrease in cancer patients with septic shock, followed by an increase in 2016. Mortality rates at 30 days and 1 year showed a decline since 2011. Adjusted HRs for 30-day mortality indicated higher risk with increasing age, presence of comorbidities, and specific cancer types. Notably, admissions in 2016 and 2017 showed improved 30-day mortality rates compared to 2009. Among cancer patients with septic shock, 14.7% had neutropenia, which was associated with a 30-day mortality rate of 44.5%. Patients without neutropenia were older and had higher comorbidity burdens. Neutropenic patients had better survival rates at both 30 days and 1 year. Among cancer patients with septic shock, 12.8% experienced AKI requiring dialysis, with 77.9% of these patients recovering within 30 days. Those needing dialysis were younger and had lower comorbidity scores. Female sex, younger age, and absence of hypertension, diabetes, heart failure, or liver cirrhosis reduced the likelihood of developing septic AKI. The occurrence of AKI requiring dialysis was associated with higher 1-month mortality rates. The overall 2- year mortality rate was 85.1%. More non-survivors required dialysis during hospitalization. Higher age, male gender, liver cirrhosis, and higher comorbidity scores were associated with higher 2-year mortality rates. Conclusions Recently, mortality rates of septic shock among cancer patients have decreased across all cancer types. Even with neutropenia, mortality rates did not worsen, suggesting that intensive care should not be withheld solely on neutropenia status. In septic AKI patients requiring dialysis, mortality rates were notably high, especially among males, hematologic cancer patients, and those with multiple comorbidities.
Key words ; Cancer patients with septic shock, Mortality, Neutropenia, Acute Kidney Injury|배경
발달하고 있는 암 진단과 치료 기술에 암 발생률과 치료기간이 증가되고 있으며 이에 따른 응급실 방문 및 처치 또한 늘어나고 있다. 장기간의 항암치료와 그에 따른 합병증은 다양한 장기 손상으로 발현될 수 있다. 그 중 패혈증 쇼크는 암 환자 사이에서 생명을 위협하는 가장 흔한 합병증이다. 최근 연구에 따르면, 패혈증을 겪는 암 환자의 생존 결과가 개선되고 있지만, 이들 환자의 응급실 치료는 방대한 자원 소모와 관련 비용으로 인해 어려움을 겪고 있다. 또한 패혈증 쇼크를 겪는 암 환자 중 적지 않는 수에서 호중구 감소증이 발생하지만, 이에 따른 패혈성 쇼크 암환자의 예후에 미치는 영향은 아직까지 명확하게 규명되지 않았다. 또한, 패혈성 쇼크는 흔하게 신부전 장애를 동반할 수 있고, 이는 환자의 의료비 상승 및 사망률과 관련이 있다고 알려져 있다. 이에 저자들은 암 환자들 중 치료과정 중 패혈성 쇼크로 응급실로 내원한 국내 환자들 자료를 분석하여, 패혈성 쇼크를 겪는 암 환자의 사망 추이를 평가하고, 이들에서 호중구 감소증 동반 시 예후에 미치는 영향을 평가하며, 급성신부전의의 동반 요인을 탐구하여 치료 전략을 개선하기 위해 국가보건정보 데이터베이스를 기반으로 한 인구 기반 코호트 연구를 진행하였다.
방법
본 연구는 2009년부터 2017년까지의 데이터를 활용한 대한민국 국가보건정보 데이터베이스를 기반으로 한 인구 기반 코호트 연구로 응급실을 통해 패혈성 쇼크로 내원한 환자들을 임상 감시 기준을 사용하여 식별하였고, 이 중 암 환자는 입원 90일 전에 암 진단 코드가 등록된 것으로 정의하였다. 생존자와 비생존자 사이의 특성을 30일과 1년 사망률을 통해 평가하였고, 단 변량 분석에서 유의하였던 변수들, 나이, 성별, 찰슨 동반 질병 지수(Charlson Comorbidity Index)들을 보정하여 다변량 분석을 진행하였다. 또한 호중구 감소증의 존재와 사망률 간의 관련성을 확인하였다. 패혈성 쇼크로 인한 신장 손상에 대한 투석 필요성을 확인하였고 투석 필요성 및 2년 생존률과 관련된 변수를 확인하기 위해 다변량 회귀 분석과 Cox 비례 위험 모형을 사용하였다. 모든 분석은 양측 P 값 < 0.05를 사용하였으며, SAS Enterprise Guide 버전 7.1을 사용하였다.
결과
2009년부터 2017년까지 대한민국 응급실을 내원한 322,526명의 패혈성 쇼크 환자 중, 90일 이내 암 진단 코드가 확인된 환자는 43,850명 (13.6%) 이었다. 이중 18세 미만이거나 데이터 누락이 있는 환자를 제외한, 43,466명의 환자가 연구에 등록되었다. 패혈증 쇼크 암환자들의 30일 사망률은 22,639명 (52.1%), 1년 사망률은 35,325명 (81.3%)였다. 패혈증 쇼크 암환자들은 2016년부터 증가하는 추세이나, 이들의 30일 및 1년 사망률은 2011년 이후 꾸준히 감소 추세였다. 가장 높은 유병율을 보인 암은 순서대로 폐암 (15.5%), 간암 (14.4%), 대장암 (10.3%), 위암 (8.5%), 담낭암 (4.6%), 췌장암 (4.5%), 백혈병 (4.4%), 비호지킨 림프종(3.4%)이었으며, 30일 사망율이 가장 높은 순으로는 폐암 (62.9%), 간암 (59.8%), 백혈병 (54.9%), 췌장암 (53.0%), 위암 (50.6%), 비호지킨 림프종 (49.7%), 담낭암 (43.6%), 대장암 (41.9%)이었다. 패혈증 쇼크 암 환자 중 14.7%가 호중구 감소증이 동반되었으며, 이들의 30일 사망률은 44.5%였다. 호중구 감소증이 없는 환자들은 더 나이가 많으며, 동반 질환 부담이 더 컸다. 패혈증 쇼크 암 환자 중 호중구 감소증이 있는 환자들은 30일과 1년 생존률 모두 호중구 감소증이 동반되지 않는 패혈증 쇼크 암 환자들보다 높았다. 패혈증 쇼크 암 환자 중 12.8%는 투석을 필요로하는 급성 신장 손상을 겪었으며, 이 중 77.9%는 30일 이내에 회복되었다. 투석이 필요한 환자들은 더 어렸으며, 동반 질환 점수가 낮았다. 여성 성별, 젊은 나이, 고혈압, 당뇨병, 심부전 또는 간경변증의 부재는 감염성 신장 손상 발생 가능성을 낮추었다. 투석을 필요로 하는 감염성 신장 손상의 발생은 1개월 사망률을 높였고 이들의 2년 사망률은 85.1%였다. 입원 중 투석이 필요한 환자들은 비생존자들 사이에서 더 많았습니다. 높은 나이, 남성, 간경변증 및 높은 동반 질환 점수는 2년 사망률과 관련이 있는 변수들이었다.
결론
최근 몇 년 동안 암 환자들에서 패혈성 쇼크로 인한 사망률은 암의 종류에 관계없이 점차 감소하였다. 호중구 감소증이 있더라도 패혈성 쇼크의 사망률이 유의하게 악화되지 않았다. 이는 호중구 감소증 동반 여부만으로 패혈증 쇼크 암환자들의 추가적인 집중 치료등을 보류하는 것은 적절하지 않음을 시사한다. 패혈증 쇼크 암환자들에서 투석이 필요한 급성 신장 손상의 동반은 장기적인 사망률을 증가시켰다.
중심 단어
암 환자들과 감염성 쇼크; 사망률; 중성구 감소증; 급성 신장 손상Docto
Toxicology and safety study of L-tryptophan and its impurities for use in swine
No full textL-tryptophan, an essential amino acid for physiological processes, metabolism, development, and growth of organisms, is widely utilized in animal nutrition and human health as a feed additive and nutritional supplement, respectively. Despite its known benefits, safety concerns have arisen due to an eosinophilia-myalgia syndrome (EMS) outbreak linked to L-tryptophan consumed by humans. Extensive research has established that the EMS outbreak was caused by an L-tryptophan product that contained certain impurities. Therefore, safety validations are imperative to endorse the use of L-tryptophan as a supplement or a feed additive. This study was conducted in tertiary hybrid [(Landrace × Yorkshire) × Duroc] pigs to assess general toxicity and potential risks for EMS-related symptoms associated with L-tryptophan used as a feed additive. Our investigation elucidated the relationship between L-tryptophan and EMS in swine. No mortalities or clinical signs were observed in any animals during the administration period, and the test substance did not induce toxic effects. Hematological analysis and histopathological examination revealed no changes in EMS-related parameters, such as eosinophil counts, lung lesions, skin lesions, or muscle atrophy. Furthermore, no test substance-related changes occurred in other general toxicological parameters. Through analyzing the tissues and organs of swine, most of the L-tryptophan impurities that may cause EMS were not retained. Based on these findings, we concluded that incorporating L-tryptophan and its impurities into the diet does not induce EMS in swine. Consequently, L-tryptophan may be used as a feed additive throughout all growth stages of swine without safety concerns