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Acute pancreatitis as an early sign of pancreatic cancer; a retrospective, matched cohort study
No full textBackground and aims: Pancreatic ductal adenocarcinoma (PDAC) often presents as acute pancreatitis (AP). However, data on the clinical outcomes of PDAC initially presenting as AP are limited. We aimed to assess the clinical features of PDAC that manifest as AP.
Methods: We reviewed the PDAC database at the Asan Medical Center between 2010-2016. Our study included 77 patients with PDAC who presented with AP (PDAC-AP group) and 154 age-gender-matched PDAC patients as controls (PDAC-other group). Patients' demographics, disease characteristics, and outcomes were compared between both groups.
Results: Acute pancreatitis was an initial symptom in 1.12% of the patients with PDAC (77 of 6,821). Approximately 81.8% of the patients had clinically mild pancreatitis, and 91% were diagnosed with PDAC within two months of presentation with AP. Main tumor size was significantly smaller in the PDAC-AP group than in the PDAC-other group (PDAC-AP: 2.59 ± 1.21 cm vs. PDAC-other: 3.73 ± 1.78 cm, p < 0.01). The PDAC-AP group patients were diagnosed earlier than those in the PDAC-other group (PDAC-AP: stage 1-2, 80.6% vs. PDAC-other: 46.7%, p < 0.01). The proportion of resectable PDAC was significantly higher in the PDAC-AP group (PDAC-AP: 64.9% vs. PDAC-other: 50%, p < 0.01). Overall survival was significantly longer in the PDAC-AP group than in the PDAC-other group (30.2 months vs. 19.9 months, p = 0.03).
Conclusions: In patients who presented with clinical AP, PDAC was identified at an earlier stage, and these patients showed better survival rates. These results suggest that AP may be an early sign of PDAC
Photophysical Studies on Boron- and Nitrogen-Doped Multi-Resonance Emitters with Polycyclic Aromatic Hydrocarbons
No full textWe studied the introduction of polycyclic aromatic hydrocarbon (PAH) groups such as pyrene and phenylanthracene into the para position of the boron atom of the DABNA core to provide enhanced fluorescence for a hyperfluorescent (HF) system. The two synthesized compounds, BuDABNA-pyr and BuDABNA-phant, exhibit emission in the blue region (~ 466 nm) in toluene solution and high photoluminescence quantum yield (PLQY) of 100%. Furthermore, BuDABNA-pyr shows a reduced T1 state energy level when compared to BuDABNA without PAH substituents. It was also observed from the decay curves that the compounds are highly fluorescent without a delayed component, which can be confirmed by the short lifetime of the PMMA film. Therefore, both compounds can be applied to emitters as dopants in blue HF-OLED systems.|파이렌 및 페닐안트라센과 같은 다환 방향족 탄화수소기(PAHs)를 DABNA 코어의 붕소 원자 파라 위치에 도입하여 초형광(HF) 시스템에 향상된 형광을 제공하는 방법을 연구했습니다. 합성된 두 가지 화합물, BuDABNA-pyr 및 BuDABNA-phant 은 톨루엔 용액에서 청색 영역(~ 466nm)의 발광과 100%의 높은 광발광 양자 효율(PLQY)을 나타냈습니다. 또한, BuDABNA-pyr 은 PAH 치환체가 없는 BuDABNA 와 비교했을 때 감소된 T1 state 에너지 레벨을 보여줍니다. 또한 붕괴 곡선에서 화합물이 지연 요소 없이 높은 형광성을 띠는 것을 관찰할 수 있었는데, 이는 PMMA 필름의 짧은 수명으로 확인할 수 있습니다. 따라서 두 화합물 모두 청색 HF-OLED 시스템에서 도펀트로서 이미터에 적용할 수 있습니다.Maste
Prediction of [177Lu]Lu-DOTA-TATE therapy response using the absorbed dose estimated from [177Lu]Lu-DOTA-TATE SPECT/CT in patients with metastatic neuroendocrine tumour
No full textBackground: Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE has shown efficacy in patients with metastatic neuroendocrine tumours (NETs). Personalised dosimetry is crucial to optimise treatment outcomes and minimise adverse events. In this study, we investigated the correlation between the tumour-absorbed dose (TAD) estimated from [177Lu]Lu-DOTA-TATE SPECT/CT and the therapeutic response.
Method: A retrospective analysis was conducted on patients with advanced well-differentiated NETs grades 1-3 who underwent PRRT and exhibited greater uptake than liver on pre-therapeutic [68Ga]Ga-DOTA-TOC PET/CT. Target lesions were selected based on the RECIST 1.1 and PERCIST 1.0 criteria using [177Lu]Lu-DOTA-TATE SPECT/CT and pre-therapeutic contrast-enhanced CT scans. For anatomical image analysis, the sum of the longest diameter (SLD) of the target lesions was measured using the RECIST 1.1 criteria for patient-based analysis and the longest diameter (LD) of the target lesion using the RECIST-L criteria for lesion-based analysis. Standardised uptake values (SUVs) were measured on SPECT/CT images, and TADs were calculated based on the SUVs. Dosimetry was performed using a single SPECT/CT imaging time point at day 4-5 post-therapy. Statistical analyses were conducted to investigate correlations and determine the target lesion responses.
Results: Twenty patients with primary tumour sites and hepatic metastases were included. Fifty-five target lesions, predominantly located in the pancreas and liver, were analysed. The cumulative TAD (lesion-based analysis: r = 0.299-0.301, p = 0.025-0.027), but not the cycle 1 SUV (lesion-based analysis: r = 0.198-0.206, p = 0.131-0.147) or cycle 1 TAD (lesion-based analysis: r = 0.209-0.217, p = 0.112-0.126), exhibited a significant correlation with the change in LD of the target lesion. Binary logistic regression analysis identified the significance of the cumulative TAD in predicting disease control according to the RECIST-L criteria (odds ratio = 1.031-1.051, p = 0.024-0.026).
Conclusions: The cumulative TAD estimated from [177Lu]Lu-DOTA-TATE SPECT/CT revealed a significant correlation with change in LD, which was significantly higher for the cumulative TAD than for the cycle 1 SUV or TAD. A higher cumulative TAD was associated with disease control in the target lesion. However, considering the limitations inherent to a confined sample size, careful interpretation of these findings is required. Estimation of the cumulative TAD of [177Lu]Lu-DOTA-TATE therapy could guide the platform towards personalised therapy
Comparative study of extraperitoneal singe-port robot-assisted radical prostatectomy and transperitoneal multiport robot-assisted radical prostatectomy using propensity score matching
No full textBackground: With the introduction of the da Vinci single-port (SP) robot platform, surgery in a narrow space has become easier, and using this, extraperitoneal radical prostatectomy has been frequently performed recently. However, studies comparing it with existing methods are still lacking. Therefore, in this study, we compared the initial extraperitoneal single-port robot-assisted radical prostatectomy (spRARP) with intraperitoneal multiport robot-assisted radical prostatectomy (mpRARP) and tried to investigate the feasibility of extraperitoneal spRARP.
Methods: We retrospectively analyzed patients who underwent RARP performed between January 2019 and April 2023. A total of 184 consecutive patients were enrolled in this study: 64 underwent spRARP and 120 underwent mpRARP. Patient characteristics before and after surgery were investigated, and period of passing gas, foley maintenance period, length of hospital stay, and pain changes were compared and analyzed to estimate post-surgery recovery. To address inherent biases stemming from differing patient characteristics at baseline, we performed an additional analysis after propensity score matching (PSM) (ratio, 1:1).
Results: After PSM, both the spRARP and mpRARP groups consisted of 64 patients each. On preoperative examination, there were no significant differences in prostate-specific antigen level, Gleason score (GS), prostate volume, magnetic resonance imaging T stage, or Prostate Imaging-Reporting and Data System score between the two groups. Following surgery, there were no significant differences in operative and console time between the two groups. Notably, the estimated blood loss was considerably lesser in the spRARP group than in the mpRARP group (P=0.049). When comparing pathologic outcomes, the GS, T stage, positive surgical margin, extracapsular extension, and seminal vesicle invasion rates showed no significant differences between the two groups. Four patients who underwent spRARP and six who underwent mpRARP suffered Clavien-Dindo classification grade 3 and 4 complications. After 3 months, there were no significant differences in incontinence or potency between the two groups. However, even after PSM, the period of passing gas was earlier in the spRARP group than in the mpRARP group.
Conclusions: In this study, both the extraperitoneal spRARP and transperitoneal mpRARP groups exhibited similar complication rates and surgical outcomes. Furthermore, the spRARP group had a short surgical time and demonstrated early recovery. Therefore, extraperitoneal spRARP is a feasible procedure that is expected to become increasingly popular in the future
Hypothalamic astrocyte NAD+ salvage pathway mediates the coupling of dietary fat overconsumption in a mouse model of obesity
No full textNicotinamide adenine dinucleotide (NAD)+ serves as a crucial coenzyme in numerous essential biological reactions, and its cellular availability relies on the activity of the nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed salvage pathway. Here we show that treatment with saturated fatty acids activates the NAD+ salvage pathway in hypothalamic astrocytes. Furthermore, inhibition of this pathway mitigates hypothalamic inflammation and attenuates the development of obesity in male mice fed a high-fat diet (HFD). Mechanistically, CD38 functions downstream of the NAD+ salvage pathway in hypothalamic astrocytes burdened with excess fat. The activation of the astrocytic NAMPT-NAD+ -CD38 axis in response to fat overload induces proinflammatory responses in the hypothalamus. It also leads to aberrantly activated basal Ca2+ signals and compromised Ca2+ responses to metabolic hormones such as insulin, leptin, and glucagon-like peptide 1, ultimately resulting in dysfunctional hypothalamic astrocytes. Our findings highlight the significant contribution of the hypothalamic astrocytic NAD+ salvage pathway, along with its downstream CD38, to HFD-induced obesity
Review of Domestic and International Performance Evaluation in Regulatory Process for In Vitro Diagnostics, and Clinical Performance Evaluation of the PIVKA-II Assay Kit
No full text체외진단의료기기란 사람이나 동물에서 유래한 검체를 대상으로 체외에서 검사하 여 의학적 판단에 필요한 임상적 정보를 제공하는 의료기기다. 체외진단의료기기를 사용한 검사에서 오류가 발생하여 잘못된 의학적 결정을 내리게 될 경우 환자의 건강 과 생명에 영향을 미칠 수 있으므로 체외진단의료기기는 시장에 판매되기 전 안전성 과 유효성을 확인하기 위한 허가절차를 거쳐야 한다. 체외진단의료기기 중 개인 또는 공중에 미칠 수 있는 잠재적 위해도가 높은 제품은 허가절차에서 안전성 및 유효성을 입증하기 위해 더 많은 성능평가 자료를 제출해야 한다. 체외진단의료기기에 대한 허 가절차와 성능평가 과정은 국가별로 규정이 상이해 허가에 필요한 사항을 파악하는 데 어려움이 있어 해외 시장 진입 시의 장벽으로 작용할 수 있다. 따라서 본 연구는 글로벌 의료기기 시장에서 1, 2위 규모를 차지하고 있는 미국, 유 럽과 국내의 체외진단의료기기 허가절차 및 성능평가 규정을 조사하고, 성능평가 수 행의 예시로 “HISCL PIVKA-II Assay Kit”의 임상적 성능시험을 국내 규정에 따라 수 행했다. PIVKA-II는 간암의 진단 및 예후판정에 활용되는 종양표지자다. 간암의 유병률과 사망률이 높은 국내에서는 PIVKA-II 측정에 사용되는 체외진단시약 “HISCL PIVKA- II Assay Kit”가 3등급에 해당하여 국내에서의 허가를 위해 기술문서와 임상적 성능 시험 자료 제출이 요구된다. 이에 따라 임상적 성능시험으로 “HISCL PIVKA-II Assay Kit”의 임상적 유효성 평가와 기허가 기기인 “Lumipulse G PIVKA-II”와의 비교평 가를 서울아산병원에서 수행했고, 분석적, 임상적 성능 평가 항목 중 정밀도, 직선성, 상관성, 기대값을 환자 검체를 분석해 평가했다. 국제적으로 통용되는 지침인 CLSI guideline을 참고해 정한 평가 프로토콜을 따라 시험을 수행하고, 기허가 기기의 임상 시험자료 및 관련 문헌에서 정한 기준을 참고한 평가 기준으로 결과를 판정했다. 평가 결과 정밀도, 직선성, 상관성 모두 평가 기준을 만족하였고, 기허가 기기와 좋은 일치 율을 보였다. 임상적 성능시험 데이터 분석 결과로 결과보고서를 작성하고 “HISCL PIVKA-II Assay Kit”의 허가를 위한 임상적 성능시험 자료로 식약처에 제출하였다. 아울러 한국, 미국, 유럽의 허가절차와 성능평가의 규정에 대한 조사 내용을 비교하 여 각 규제 당국에서 PIVKA-II Assay Kit의 성능평가를 한다고 가정했을 때 따라야 할 절차와 성능평가 시 참고해야 할 사항을 정리했다. 본 연구를 통해 한국, 미국, 유럽의 허가과정, 제출문서, 평가 절차의 세부 사항은 차 이가 있지만 잠재적 위해도가 높은, 즉 높은 등급의 기기는 더 복잡한 허가절차와 더 많은 성능평가 자료가 요구된다는 공통점을 확인했다. 또한, 각 규제 당국의 성능평가 지침은 평가 항목, 프로토콜, 평가 기준과 같은 실무적인 부분에 대한 구체적인 지침이 명시되어 있지 않아 CLSI guideline과 같은 국제 표준 지침과 관련 문헌을 참고하여 임 상적 성능시험 계획을 수립하고 규제당국과 협의가 필요함을 확인했다.Maste
Pathological Analysis of Claudin 18.2 Expression in Patients with Gastric Cancer
No full textClaudin 18.2 is a tight junction protein expressed on the cellular surface of normal gastric epithelium, and its expression is frequently upregulated in gastric cancer. Due to the recent success of zolbetuximab - a monoclonal antibody agent targeting claudin 18.2 - in two phase 3 trials (SPOTLIGHT and GLOW), it has emerged as a promising therapeutic target in gastric cancer. In this systematic study, the same antibody clones and evaluation methods were utilized for assessing claudin 18.2 expression, to provide the consistency of the overall analysis.
Part 1 of this study focused on investigating the clinicopathologic features and survival outcomes of claudin 18.2 positive tumors in patients with stage I-III gastric cancer. This study aimed to provide insights for the potential application of claudin 18.2-targeted treatment in earlier stages of gastric cancer. Claudin 18.2 positivity was observed in 46.5% of the total 299 patients, with slightly higher rate among stage I patients (51.1%). Claudin 18.2 positivity was associated with a younger age (median, 61 vs 66 years, p<0.001), a shallower depth of invasion (p=0.014), Borrmann type 4 morphology (p=0.008) and diffuse histological type (p=0.011). However, it was not an independent prognostic factor in a localized setting. These findings aligned with previous research conducted in patients with advanced gastric cancer.
In part 2, the heterogeneity of claudin 18.2 expression was investigated in 166 patients with stage IV gastric cancer. paired tissue samples of primary and metastatic tumors from 135 of these patients were thoroughly analyzed, revealing a concordance rate over 50%. Notably, patients with peritoneal metastasis displayed the highest rate of claudin 18.2 positivity, suggesting that patients with peritoneal metastasis could potentially derive the greatest benefit from claudin 18.2-targeted therapy in terms of systemic disease control. Furthermore, this study provided specific cutoff values to maximize the efficacy of claudin 18.2-targeted treatment, recommending a threshold of 120 for H-score and 30% for the percentage of tumor cells exhibiting moderate to strong intensity. Additionally, this study revealed a high prevalence of intratumoral heterogeneity, pointing out the limitations of endoscopic biopsy in representing the entire tumor characteristics. These findings may provide a deeper insight for the complexities of claudin 18.2 expression status in stage IV gastric cancer.Maste
Greenhouse gas emissions and net energy production of dark fermentation from food waste followed by anaerobic digestion
No full textThere are diverse estimations regarding the carbon reduction effects of alternative hydrogen production tech nologies. This study assessed the greenhouse gas (GHG) emissions and energy balance of a two-stage process combining dark fermentative hydrogen production and anaerobic digestion from food waste using the cradle-to gate life cycle assessment (LCA). The system boundary included collection and transportation, pretreatment and feedstock storage, dark fermentation, H2 purification, anaerobic digestion and heat and power generation and the estimated GHG emission was compared with a single anaerobic digestion of food waste. GHG emission of the biohydrogen production was estimated as 2.48 kg CO₂-eq per kg H₂ without considering avoided emissions from heat and power generation. The environmental impacts were majorly influenced by electricity use. The net energy ratio of the two-stage process was calculated to be 8.18, confirming a net energy gain and the potential GHG emission avoidance for electricity and heat use. Given that the single-stage anaerobic digestion of 16 tons of food waste is replaced by the two-stage dark fermentation process, 76.6 kg CO₂-eq would be avoided. Sensitivity analysis revealed that energy-saving strategies are the most sensitive factors for achieving positive net energy production and low global warming potential
Effect of two types of polymeric binders on the performance of high-capacity and solvent-free electrodes in lithium-ion batteries
No full text리튬 이차전지는 스마트폰, 무선이어폰, 에너지 저장장치(ESS), 전기자동차와 같은 다양한 분야에 적용되며, 장수명, 고출력을 위한 고에너지 밀도를 갖춘 전지 소재 및 배터리 제조공정에 대한 연구가 활발하게 진행되고 있다. 이처럼 리튬 이온 배터리의 수요가 증가하며 배터리의 원가를 낮추기 위해 전지 소재 성능 향상 및 전지 제조공정 비용 절감 기술이 주목받고 있다.
전지 소재 측면에서 고용량 고출력의 차세대물질로 Si계 음극활물질의 부피팽창을 완화하며 전극에 높은 안정성과 성능 향상에 기여하는 바인더의 중요성이 대두되고 있다. 전지 제조공정 측면에서 고로딩의 전극을 제조할 수 있을 뿐만 아니라 기존의 습식공정 대비 많은 이점을 지니는 건식공정에 대한 연구가 활발히 진행되고 있다. 특히 건식 전극은 용매를 사용하지 않고 전극의 형태를 유지하기 위해 바인더의 역할이 매우 중요하다.
본 연구에서는 SiOx 5 % ~ 30 % 와 Graphite를 복합 음극활물질로 사용하여 상업용 수분산 바인더 SBR(styrene-bytadiene rubber), CMC(carboxy-methyl cellulose)에 적용하였을 때 최적 SiOx 비율을 연구했다. 이후 SiOx의 부피팽창에 대한 기계적 안정성을 부여하는 AM monomer와 AA monomer의 자유 라디칼 중합으로 제작된 P(AM-AA) 공중합체 바인더의 성능을 확인하고자 앞선 SiOx/C 최적 비율의 고용량 음극 전극에 적용했다. 중합한 바인더의 물리화학적 성능을 평가하기 위해 FT-IR, DSC, TGA, Rheology test, 전극저항 평가, 접착력 평가, 전해액 착수 등의 실험과 0.005 ~ 1.5 V 전압 범위에서 사이클 수명, 율속 특성, CV 분석, 임피던스 분석을 진행했다.
또한, 리튬이온 배터리 제조공정에서 기존 습식공정의 한계점을 극복하며 용매를 사용하지 않고 고로딩의 자립형 양극 건식 전극을 제작해 PTFE 고분자 바인더와 PVDF 고분자 바인더의 비율에 따른 건식 전극의 특성 평가 실험을 비교 분석했다. 고로딩의 건식 전극에 적용된 바인더의 물리화학적 성능을 평가하기 위해 전극저항 평가, 접착력 평가 SAICAS 등의 실험과 2.7 ~ 4.2 V 전압 범위에서 사이클 수명, 율속 특성, CV 분석, 임피던스 분석을 진행했다.
|Lithium-ion batteries (LIBs) are being used in various fields such as smartphones, wireless earphones, energy storage system, and electric vehicles. Intensive research efforts are currently being directed towards the development of battery materials and manufacturing techniques, with the goal of producing batteries that boast high energy density, extended longevity, and superior performance. With the rising demand for lithium-ion batteries, there is a growing focus on advancing technologies to enhance the performance of battery materials and to reduce the costs associated with the battery manufacturing process, ultimately aiming to decrease the overall cost of batteries.
Regarding battery materials, the significance of binders is coming to the forefront as a next-generation material. These binders are essential for high-capacity and high-output applications, as they mitigate the volume expansion in silicon-based anode active materials, thereby contributing to the enhanced stability and performance of electrodes. In terms of the battery manufacturing process there is active research on the dry process method. This approach is not only capable of producing high-loading electrodes but also offers numerous advantages compared to the traditional wet process. Specifically, in the case of dry electrodes, the role of the binder becomes crucial in maintaining the electrode's shape, especially as it eliminates the need for a solvent.
In this study, we investigated the optimal SiOx ratio for application in commercially available water-dispersed binders, namely SBR (styrene-butadiene rubber) and CMC (carboxymethyl cellulose). This was done using a composite anode active material comprised of 5 % to 30 % SiOx and graphite. Subsequently, to evaluate the performance of the P(AM-AA) copolymer binder, synthesized through free radical polymerization of AM and AA monomers, we applied it to a high-capacity cathode electrode. This was done to assess its mechanical stability against the volume expansion of SiOx, using the optimal SiOx/C ratio. To evaluate the physical and chemical performance of the polymerized binder, various experiments were conducted. These included FT-IR, DSC, TGA, rheology tests, evaluations of electrode resistance, adhesion tests, and analyses of electrolyte uptake. Additionally, to assess the cycling performance, rate capability, and CV test within the voltage range of 0.005 to 1.5 V, an EIS test was also performed.
Additionally, moving beyond the usual wet process used in making lithium-ion batteries, we created a high-capacity anode dry electrode without using solvents. We also carried out tests to see how the dry electrode behaves with different amounts of PTFE and PVDF polymer binders. To evaluate the physical performance of the binder applied to the high-loading dry electrode, experiments such as electrode resistance evaluation, adhesion tests, and SAICAS analyses were conducted. Additionally, to assess the cycling performance, rate capability, and CV test within the voltage range of 2.7 to 4.2 V, an EIS test was also performed.Maste
Stomach clusterin as a gut-derived feeding regulator
No full textThe stomach has emerged as a crucial endocrine organ in the regulation of feeding since the discovery of ghrelin. Gut-derived hormones, such as ghrelin and cholecystokinin, can act through the vagus nerve. We previously reported the satiety effect of hypothalamic clusterin, but the impact of peripheral clusterin remains unknown. In this study, we administered clusterin intraperitoneally to mice and observed its ability to suppress fasting-driven food intake. Interestingly, we found its synergism with cholecystokinin and antagonism with ghrelin. These effects were accompanied by increased c-fos immunoreactivity in nucleus tractus solitarius, area postrema, and hypothalamic paraventricular nucleus. Notably, truncal vagotomy abolished this response. The stomach expressed clusterin at high levels among the organs, and gastric clusterin was detected in specific enteroendocrine cells and the submucosal plexus. Gastric clusterin expression decreased after fasting but recovered after 2 hours of refeeding. Furthermore, we confirmed that stomachspecific overexpression of clusterin reduced food intake after overnight fasting. These results suggest that gastric clusterin may function as a gut-derived peptide involved in the regulation of feeding through the gut-brain axis. [BMB Reports 2024; 57(3): 149-154]