Otemae Hospital

Introduction: Type 2 Diabetes Mellitus (T2DM) affects over 537 million individuals worldwide, with cases expected to rise to 783 million by the year 2045. Metformin is the primary treatment, but its efficacy varies due to dietary influences. Growing evidence suggests that macro- and micronutrients interact with metformin, influencing its therapeutic effects. However, these interactions remain poorly understood. This review aims to bridge this knowledge gap by synthesizing recent findings on metformin-nutrient interactions to inform optimized therapeutic and dietary strategies. Objective: The objective of this systemic review is to investigate the impact of macro- and micronutrients on metformin anti-diabetic activity. Methods: This systematic review adheres to PRISMA guidelines, focusing on systematic reviews, meta-analyses, and experimental studies from PubMed, Scopus, and Web of Science. The research was carried out from September to October 2024. The studies were evaluated for quality using the GRADE tool and the risk of bias was assessed using the Cochrane tool. Results and conclusion: 132 research studies were identified and subjected to an eligibility assessment. After a careful evaluation, 33 studies were included in this systematic review. The Cochrane tool used for assessing the risk of bias revealed that 22 studies had a high risk of bias, while 24 studies failed to meet the GRADE criteria. Most of the studies showed homogeneity in their findings, with X2=85.7%>50%. It was concluded that high saturated fat intake reduces metformin’s effect alternatively, nutrients like leucine enhance metformin efficacy through mechanisms involving the AMPK pathway, promoting lipid oxidation and glycemic improvements. Micronutrients such as calcium, magnesium, and potassium play essential roles in glucose metabolism and insulin signaling. These minerals are absorbed through OCT1 transporters, the same transport pathway used by metformin for cellular uptake. Clinical trials have demonstrated that adequate dietary intake of these micronutrients stabilizes blood glucose levels when combined with metformin. In conclusion, it is suggested that dietary composition should be an integral component of T2DM management for patients on metformin therapy.

【背景および目的】急性期脳卒中患者における継続的なリハビリテーション（リハビリ）は，機能的転帰の改善や合併症予防に重要である．本研究は，休日リハビリの導入が退院時機能的転帰や合併症発生率に与える影響を明らかにすることを目的とした．【方法】2021年4月から2024年3月に入院した急性期脳卒中患者402名を対象に，5–6日間のリハビリ（従来）群と従来に加えて休日にリハビリを導入した群（休日群）を後ろ向きに比較した．退院時機能的転帰（mRS），合併症発生率を調査し，傾向スコアマッチングを実施した．【結果】休日群は，良好な機能的転帰（mRS≤2）の割合が増加し（72.1% vs 57.8%，p=0.012），合併症の発生率が低下した（4.5% vs 14.9%，p=0.003）．【結論】休日リハビリの導入は，機能的転帰の改善や合併症予防に有効であった．

A 76-year-old man with sigmoid colon cancer and gastric cancer was referred to our hospital because of severe anemia. Computed tomography revealed peritoneal dissemination and lung metastasis. For diagnoses of cStage Ⅳa sigmoid cancer and cStage ⅣB gastric cancer, palliative laparoscopic sigmoidectomy and distal gastrectomy were planned in order to avoid tumor hemorrhage and intestinal obstruction. Intraoperative findings suggested cancer dissemination on the pelvic peritoneum, thus laparoscopic Hartmann's procedure and distal gastrectomy were performed. The final diagnosis was sigmoid colon cancers, ①pT4, ②pT2N2aM1c2(P2, PUL1), pStage Ⅳc and gastric cancer, pT4aN1M1(PER), pStage Ⅳ. The resected specimen showed collision tumors consisting of sigmoid colon cancer(CK20+/CK7-)and dissemination of gastric cancer (CK20-/CK7+)confirmed by immunohistochemistry. Postoperatively, the patient underwent chemotherapy for gastric cancer. We report here a rare case of collision tumor consisting of a sigmoid colon adenocarcinoma and peritoneal dissemination of gastric adenocarcinoma.

Pregnant women with glucose intolerance often have large infants, even with strict glycemic control. We examined the expression of amino and fatty acid metabolic transporters in the placentas of such mothers to clarify the role of factors other than glucose transport resulting in giant infants. Deliveries at our hospital between 2017 and 2022 were assessed. Immunohistochemical staining of membrane transporters related to glucose, amino acid, and fatty acid transport was performed using postpartum placental tissue. Stained areas were classified and scored, and compared using the Mann-Whitney U test. Multiple logistic regression analysis was performed for large for gestational age infant as the outcome and maternal age, prepartum body mass index, primipara/multipara, gestational week, and glucose intolerance as confounding factors. Among 1725 subjects, 101 met the inclusion criteria and were analyzed (glucose-intolerant [GI] group, n = 61; non-GI group, n = 40). Per unit villus, there was decreased expression of amino acid-related transporters. However, per unit placenta, the immunohistochemical staining scores for glucose, amino acid, and fatty acid transport were significantly higher in the GI than in the non-GI group. Multiple logistic regression analysis showed that L-type amino acid transporter 1 (LAT1, odds ratio [95% confidence interval]: 12.35 [2.93-52.05], p < 0.001) and placenta-plasma membrane fatty acid-binding protein (placenta-FABPpm, 6.27 [1.64-23.88], p = 0.007) were significantly higher in the GI than in the non-GI group. Activation of LAT1 and placenta-FABPpm expressions observed in the placentas of glucose-intolerant women despite glycemic control indicate that nutrients other than blood glucose should also be effectively managed.

Case 1:A 73-year-old man was transported to our hospital for evaluation of sudden onset of chest pain, back pain, and dyspnea. We initially misdiagnosed him with advanced esophageal cancer accompanied by mediastinal metastasis;however, subsequent multi-detector row computed tomography (MDR-CT) confirmed the diagnosis. We performed coil embolization of a bronchial artery aneurysm and thoracic endovascular aortic repair( TEVAR) to seal the root of the bronchial artery. Case 2:An 81-year-old woman with a one-week history of fever and cervical pain was diagnosed with a ruptured infected thoracic aneurysm. She underwent the same treatment as described in Case 1. Physicians should consider it as a differential diagnosis of mediastinal hematoma.

AimAlterations in microbial composition of gut microbiota due to antibiotics (ATB) may lead to resistance to immune checkpoint inhibitors (ICIs). This study aimed to assess the impact of ATB use on therapeutic response in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab.MethodsThis study retrospectively analyzed 105 patients with HCC treated with atezolizumab plus bevacizumab as a primary systemic therapy from prospectively-registered, multicenter, cohorts. Nineteen patients who received prior ATB were included in the ATB (+) group; 86 patients who did not receive prior ATB were included in the ATB (-) group. The therapeutic outcomes were compared between the two groups.ResultsMost of the patients’ baseline characteristics were not significantly different between the two groups. The objective response rates according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) (30.1% vs. 11.1%; p = 0.143) and modified RECIST (mRECIST) (44.6% vs. 27.8%; p = 0.190) were not significantly different between the ATB (-) and ATB (+) groups. The disease control rates were higher in the ATB (-) group than in the ATB (+) group according to RECIST v1.1 (74.7% vs. 44.4%; p = 0.012) and mRECIST (78.3% vs. 50.0%; p = 0.020). Prior ATB use was found to be independently associated with radiological progressive disease of the first therapeutic assessment. The median progression-free survival according to RECIST v1.1 (9.1 months vs. 3.0 months; p = 0.049) and mRECIST (9.1 months vs. 3.0 months; p = 0.036), and overall survival (not reached vs. 11.4 months; p = 0.015) were longer in the ATB (-) group than in the ATB (+) group.ConclusionsPrior ATB use was associated with reduced therapeutic responses in patients with HCC receiving atezolizumab plus bevacizumab.

173 Background: Higher levels of vascular endothelial growth factor-D (VEGF-D) is a potential predictive biomarker for ramucirumab (Ram) efficacy on overall survival and progression-free survival (PFS) in Ram+FOLFIRI vs Placebo+FOLFIRI for bevacizumab (Bev) refractory metastatic colorectal cancer (mCRC). However, it is not clear whether VEGF-D acts as a predictive biomarker in pts who pretreated without Bev. RAINCLOUD showed the clinical benefit of FOLFIRI+ plus Ram for pts with recurrent CRC refractory to adjuvant chemotherapy (median PFS was 6.2 months (M); ESMO-GI 2022). RAINCLOUD-TR was designed as a prospective biomarker study estimating the association of biomarkers with Ram efficacy. Methods: Plasma sample collections were done at time points of pre-/ post-treatments in pts receiving FOLFIRI+Ram. Measurements of 17 factors (including VEGF-A, VEGF-D and PlGF) were performed by multiplex assay with Luminex technology. The high/ low groups were defined bases on the median plasma level at the baseline. Results: From September 2017 to September 2021, 81 plasma samples were collected from 48 pts and 32 pts in both pre/ and post treatment. Level of VEGF-A, VEGF-D, PlGF and TSP-2 were all significantly higher in post vs pre-treatment [Table]. The ORR analyses were as follows; VEGF-A, VEGF-D and PlGF in low vs high were 50.0%/33.3% (p=0.35, HR 1.97), 55.0% /33.3% (p=0.22, HR 2.39), and 60.0%/28.6% (p=0.35, HR 1.95). The PFS analyses were as follows; VEGF-A, VEGF-D, and PlGF in low vs high were 6.1M/6.0M (p=0.815, HR 0.92), 7.6M /5.6M (p=0.095, HR 0.56), and 8.0M/4.2M (p=0.014, HR 0.40). In other factors, low TSP-2 were better ORR (low vs high: 66.7%/20.0% (p=0.004, HR 7.54) and PFS 7.5M/4.3M (p=0.022, HR 0.45). Conclusions: In this exploratory study, PFS was numerically greater for pts with low vs high VEGF-D for Ram in pts with mCRC pretreated without Bev. VEGF-D may not be predictive biomarker, but TSP-2 may be a potential prognostic biomarker, further studies in larger cohorts are needed to confirm our results. Clinical trial information: UMIN000028678 . [Table: see text]

症例：60歳男性，糖尿病性腎症，透析歴9年．当院紹介受診・入院の7日前に左前腕自己血管使用皮下動静脈瘻（AVF）穿刺部感染を発症しバンコマイシン経静脈投与を開始した．発症日から右視力障害を自覚したが糖尿病網膜症による視力障害の既往が複数回あり自己判断で後日に眼科受診を予定した．発症8日後にAVF穿刺部感染による右内因性細菌性眼内炎合併と診断しバンコマイシン硝子体注射，発症9日後に右硝子体手術・眼内レンズ抜去術を行った．敗血症性肺塞栓症・下腿打撲創部感染も合併した．血液培養は陰性，右眼房水・AVF穿刺部浸出液・下腿打撲創からメチシリン感受性黄色ブドウ球菌を認めセファゾリン経静脈投与に変更した．AVF感染・敗血症性肺塞栓症・下腿打撲創部感染は改善し眼球摘出は免れたが，光覚は消失した．視力予後を改善し，眼球摘出を避けるためにAVF感染時に内因性細菌性眼内炎発症の可能性を考慮し早期診断・治療開始に努めるべきである．