馬斯垂克歐洲中風組織大會 ESOC at Maastricht

 

作者： 蔡昇達

馬斯垂克是荷蘭古老的城市，名稱源自拉丁語「Trajectum ad Mosam」，意為「馬斯河（Meuse）上的交叉點」，羅馬人在此建造了橋樑與定居點，作為連接科隆與北海的重要貿易站。17 世紀時，因為能跨過馬斯河的橋樑僅有兩座，故此城市為兵家必爭之地，1673 年，法國國王路易十四利用聖彼得山（Sint-Pietersberg）的高地優勢砲擊城市，輕易攻下馬斯垂克，後為了防止悲劇重演，荷蘭決定在該高地上興建聖彼得堡壘(Fort Sint Pieter)。

聖彼得堡壘 (Fort Sint Pieter)

不過大家較熟悉的，應是歷史學過的《馬斯垂克條約》（Maastricht Treaty），1992年，條約在此簽署，歐洲聯盟（EU）於是成立、共同貨幣為歐元，故馬斯垂克可以說是歐盟的誕生地。

參加會議收穫最大的，是看到台灣和世界的差距，兩年前剛到 Mayo Clinic，與同團隊的神經內科醫師，Dr. Hawkes 討論腦中風，他跟我說 Mayo Clinic 已經沒有在使用 alteplase 了，皆是使用 tenecteplase (TNK)，我覺得有些驚訝，再問了他一些問題，後來他為我分析世界三大腦中風會議，ESOC、ISC、WSC，他表示 ESOC 的水準是最高的，相當推荐參加，感謝 Dr. Hawkes 的介紹，讓我毫無懸念報名此次會議。

Dr. Hawkes 是中間那位 (Dr. Hawkes is the one in the middle.)

第一天中午的場次，有位阿根廷的醫師，Matías Alet，分享他們各醫院使用血栓溶解劑的狀況，從約一年半前，2024 年的 11 月，各醫院即開始可使用 TNK，目前全國的轉換率約為 30%。演講很精彩，但也讓我深刻看到台灣和世界的差距，依據 2024 年的數據，台灣的 GDP per capita (人均國內生產毛額)為 $34,238 USD，阿根廷是 $13,970 USD，台灣是阿根廷的 2.45 倍，但我們目前只有研究計劃可使用 TNK，可知對藥廠而言，藥物進阿根廷，可得的利潤比進台灣還要高，台灣雖有傲視世界的全民健保，卻影響了新藥、新醫材的引進，更不用說有資源或是經費自己開發新藥和新醫材。

兩天半密集的課程，更新了許多腦中風的診斷和治療知識，第二天中午時一同用餐的荷蘭中年醫師問我，「這次會議是否有什麼東西是你帶回去，即可用在病人身上的？」實在是一個相當好的問題，的確參加各個會議、課程，最後要有一個帶的走的東西，「Call for action」。仔細想想，最大的收穫有三：

1. 動脈取栓後 24 小時的收縮壓，建議控制於 130-180 mmHg，壓到 130 mmHg 以下有害(會讓腦部的灌流不足)，低於 130 mmHg 時不建議使用升壓劑升壓，優先考慮增加點滴的量以增加血管內容積。

2. 中風取栓打通血管後，可以在患側施打 alteplase (0.225 mg/kg) or TNK (0.125 mg/kg)，不會增加腦出血風險，但可以改善病人的預後 (主要在 excellent outcome, mRS= 0 or 1)，建議可選取 mTICI 2b 的病人。此建議是來自九篇大型的隨機對照試驗： CHOICE (2022), PEARL (2025), POST-TNK (2025), ANGEL-TNK (2025), DATE (2025), POST-UK (2025), ATTENTION-IA (2025), IAT-TOP (2026), CHOICE2 (2026 ISC)。

3. 取栓時及取栓後使用針劑 Tirofiban 是安全的，已有許多大型的隨機對照試驗背書(如 ATILA...)，在嚴重狹窄的血管，亦可考慮在手術前即開始滴注。

除急性治療外，也聽了到院前處置、Mobile stroke unit、復健、護理的場次，得到許多啟發，如將超音波帶上直昇機，診斷中大腦動脈阻塞，診斷率可達 90% (Cerebrovasc Dis. 2012;33(3):262-71)。此次問問題時發現場地預設的麥克風高度皆頗高，我站著還要稍微抬頭才搆得到，可見歐洲人的平均身高的確是很高(感覺上應該是預設 180 公分)。

Mobile stroke unit，搭載電腦斷層機器 (Mobile stroke unit equipped with a CT scanner)

Echo on the helicopter (TCD at left MCA)

此次也有貼 poster 分享院內的幹細胞研究，有幸得到美國佛州前輩的鼓勵： 要繼續做下去，覺得很棒。

開完會後參觀前述的聖彼得堡壘和地下洞窟，很尊敬導覽員們的專業和深入的說明，尤其是歷史文化的介紹，相當棒，像是他很仔細的說明下圖的城垛射孔，上排的孔是打山丘上下來的敵軍、下方的是打已經靠近城牆邊緣的，每個孔裡面站了三位士兵，每位射擊完後要清槍、重新裝彈藥，約要 20 秒，此時輪其他兩位射擊，持續不斷，而整個堡壘駐守 450 人，12 小時換一班，下班的軍人回馬斯垂克城裡的家，而此設計在 18 世紀時很有用，堡壘蓋好後共發生了兩次戰爭(法軍入侵)，但皆順利守住，保全了馬斯垂克城。

聖彼得堡壘的城垛射孔 (Loopholes at Fort Sint Pieter)

而地下洞窟，是早期蓋房子需要石灰岩(Lime stone)，故至地下挖，人為挖出來的，總共有超過兩萬條通道，後來已無使用石灰岩的需要，做了整治、請藝術家畫了些壁畫，改為文化古蹟、開放觀光。解說員也提到，萬億年前，此區域曾是溫暖的海底，故岩層中發現過著名的滄龍(Mosasarus)化石。

地下洞窟地圖 (Map of the underground caves)

恐龍壁畫 (Dinosaur mural)

English version: 

Maastricht is one of the oldest cities in the Netherlands. Its name derives from the Latin Trajectum ad Mosam, meaning “crossing point on the Meuse River.” The Romans built bridges and settlements here, turning it into an important trading hub connecting Cologne and the North Sea. In the 17th century, because there were only two bridges crossing the Meuse River, Maastricht became a highly strategic military target. In 1673, King Louis XIV of France took advantage of the high ground of Sint-Pietersberg and bombarded the city, capturing Maastricht with relative ease. To prevent history from repeating itself, the Dutch later constructed Fort Sint Pieter on the hilltop.

However, what most people are more familiar with is probably the Maastricht Treaty from history textbooks. Signed here in 1992, the treaty formally established the European Union and introduced the common currency, the euro. In many ways, Maastricht can truly be considered the birthplace of the EU.

The greatest takeaway from this conference was seeing the gap between Taiwan and the rest of the world. Two years ago, when I first arrived at the Mayo Clinic, I discussed stroke treatment with a neurologist on the same team, Dr. Hawkes. He told me that Mayo Clinic had already stopped using alteplase and had completely transitioned to tenecteplase (TNK). I remember being quite surprised. After asking him more about the topic, he analyzed the world’s three major stroke conferences for me — ESOC, ISC, and WSC — and told me that ESOC was the highest-level meeting among them and highly worth attending. Thanks to Dr. Hawkes’ recommendation, I registered for this conference without hesitation.

During a lunchtime session on the first day, an Argentinian physician, Matías Alet, shared how hospitals across Argentina were using thrombolytic agents. Since around November 2024 — roughly a year and a half ago — hospitals there had begun adopting TNK, and the nationwide conversion rate has already reached approximately 30%. The lecture was excellent, but it also made me acutely aware of the gap between Taiwan and the international medical landscape. According to 2024 data, Taiwan’s GDP per capita was USD 34,238, while Argentina’s was USD 13,970. Taiwan’s figure is about 2.45 times higher. Yet in Taiwan, TNK is still available only through research protocols. This suggests that, from a pharmaceutical company’s perspective, introducing the drug into Argentina may actually be more profitable than introducing it into Taiwan. Taiwan’s world-renowned National Health Insurance system is certainly admirable, but it also affects the introduction of new drugs and medical devices — not to mention the resources and funding required to independently develop innovative therapies and technologies.

After two and a half days of intensive sessions, I updated a great deal of my knowledge regarding stroke diagnosis and treatment. At lunch on the second day, a middle-aged Dutch physician asked me a simple but profound question:

“What is one thing from this conference that you can immediately bring back and apply to your patients?”

It was an excellent question. After all, the ultimate purpose of attending conferences and courses is to come away with something actionable — a true “call for action.” Reflecting carefully, my three biggest takeaways were:

1. Following mechanical thrombectomy, systolic blood pressure during the first 24 hours should generally be maintained between 130–180 mmHg. Lowering it below 130 mmHg may actually be harmful by reducing cerebral perfusion. If the blood pressure drops below 130 mmHg, vasopressors are not recommended as the first response; increasing intravenous fluid volume to improve intravascular volume should be considered first.

2. After successful thrombectomy and vessel recanalization, intra-arterial administration of alteplase (0.225 mg/kg) or TNK (0.125 mg/kg) on the affected side appears not to increase the risk of symptomatic intracranial hemorrhage, while potentially improving patient outcomes — particularly excellent outcomes (mRS 0–1). Patients with mTICI 2b reperfusion may especially benefit. This recommendation is supported by nine major randomized controlled trials: CHOICE (2022), PEARL (2025), POST-TNK (2025), ANGEL-TNK (2025), DATE (2025), POST-UK (2025), ATTENTION-IA (2025), IAT-TOP (2026), and CHOICE2 (2026 ISC).

3. The use of intravenous tirofiban during and after thrombectomy appears to be safe, supported by multiple large randomized controlled trials (such as ATILA). In cases of severe vascular stenosis, infusion may even be considered before the procedure begins.

Beyond acute treatment, I also attended sessions on prehospital stroke care, mobile stroke units, rehabilitation, and nursing care, all of which provided tremendous inspiration. One particularly fascinating example involved bringing ultrasound equipment onto helicopters to diagnose middle cerebral artery occlusion. Reported diagnostic accuracy reached as high as 90% (Cerebrovascular Diseases. 2012;33(3):262–271).

One amusing observation during the Q&A sessions was that the venue’s microphones were all set remarkably high. Even while standing, I still had to tilt my head slightly upward to reach them. It was a subtle reminder that Europeans really are tall on average — the default height honestly felt calibrated for someone around 180 cm tall.

I also presented a poster on our hospital’s stem cell research. I was fortunate to receive encouragement from a senior physician from Florida, who told me: “You should keep going. This is really impressive.”

After the conference, I visited the previously mentioned Fort Sint Pieter and the underground caves nearby. I deeply admired the professionalism and depth of the tour guides’ explanations, especially regarding the region’s history and culture. One particularly memorable example was the detailed explanation of the fortress loopholes shown below. The upper openings were designed to target enemies descending from the hillside, while the lower openings targeted enemies who had already approached the city walls. Three soldiers were stationed at each loophole. After firing, each soldier needed approximately 20 seconds to clean and reload the musket, during which the other two soldiers continued firing in rotation, creating uninterrupted defensive fire.

The fortress housed 450 soldiers in total, working in 12-hour shifts. After duty, the soldiers would return to their homes inside Maastricht. This design proved highly effective in the 18th century. After the fortress was completed, two wars involving French invasions occurred, yet the fortress successfully defended the city both times, preserving Maastricht from capture.

As for the underground caves, they were originally man-made limestone quarries. Limestone was extensively needed for construction, so people excavated underground, eventually creating more than 20,000 interconnected tunnels. Once limestone was no longer needed, the site was restored, artists were invited to create murals, and the caves were transformed into a cultural heritage site open to tourism.

The guide also mentioned that millions of years ago, this region was once part of a warm prehistoric sea. As a result, fossils of the famous Mosasaurus were discovered within these rock layers.

抗寒基因 Cold-Adaptation Gene

 

作者： 蔡昇達

今天讀到安南醫院神經內科杜宜憲醫師寫的第 254 期頭痛電子報，很有啟發：

杜醫師原文：

寒冷感知與偏頭痛的交易

大約50,000年前，人類祖先走出非洲，向高緯度遷徙。為了在寒冷的氣候中生存，人類必須適應低溫。人類第二對染色體的短臂上有一個 TRPM8 基因，是已知唯一能對「中度寒冷」產生內源性反應的溫度受體，同時也參與疼痛感知。遺傳研究發現，TRPM8 基因上游的一個變異位點（rs10166942），出現頻率與緯度呈現高度正相關：在炎熱的西非奈及利亞只有 5%；到了高緯度的芬蘭，頻率高達88%。然而，這個極具生存優勢的變異卻是一把雙面刃。它的原始等位基因（ancestral allele）對偏頭痛具有保護作用；但為了適應寒冷而演化出的 rs10166942 變異，反而是與偏頭痛風險強烈相關的 single-nucleotide polymorphism 之一。人類為了抵抗嚴寒氣候所付出的代價之一，或許正是偏頭痛，而歐洲地區的偏頭痛盛行率也確實高於非洲。演化往往伴隨著基因之間的利弊權衡，而 TRPM8 基因或許是偏頭痛在天擇中被保留的其中一種理由。

圖一、文獻中的圖片，左方可以見到帶有此變異位點的人在芬蘭(FIN)高達 88% (圓餅圖的深藍色)，在左下方的非洲國家比例皆相當低，約 5% 左右 (圓餅圖的黃色)

在美國明尼蘇達州進修的一年多的期間，常覺得住在高緯度的人(明州是美國除了阿拉斯加外緯度最高的一州)和住在低緯度的人是不一樣的，最明顯的是在寒冷的冬天，常可見他們穿著短袖在路上走，幼稚園的小朋友亦然，冬天穿短袖短褲的並不少見，而女兒和我早已冷到受不了。6-8 月的夏天亦很明顯，當地人對超過攝氏 25 度的高溫難以忍受，多要待在冷氣房中。讀了這篇基因分析的文章，我想或許每個人皆有自己適合生存的溫度和環境，也可以理解為何長住在美國的華人，退休後喜歡搬到溫暖的加州南部生活。感謝杜宜憲醫師的文獻整理和分享！

English version: 

Today, I read Issue No. 254 of the Headache Newsletter written by Dr. Yi-Hsien Tu from the Department of Neurology at An-Nan Hospital, which I found highly insightful:

Original text by Dr. Tu:

The Trade-off Between Cold Sensation and Migraine

Approximately 50,000 years ago, human ancestors migrated out of Africa toward higher latitudes. To survive in colder climates, humans had to adapt to low temperatures. On the short arm of human chromosome 2 lies the TRPM8 gene, which is currently the only known temperature receptor capable of generating an endogenous response to moderate cold and is also involved in pain perception.

Genetic studies have identified a variant located upstream of the TRPM8 gene (rs10166942), whose frequency shows a strong positive correlation with latitude: it is present in only about 5% of individuals in hot regions such as Nigeria in West Africa, but rises dramatically to as high as 88% in high-latitude regions such as Finland. However, this variant, which confers a significant survival advantage, is also a double-edged sword. The ancestral allele of TRPM8 appears to be protective against migraine, whereas the rs10166942 variant that evolved as an adaptation to cold climates is, conversely, one of the single-nucleotide polymorphisms strongly associated with an increased risk of migraine.

One of the evolutionary costs humans may have paid for adapting to harsh, cold environments could be migraine itself. Indeed, the prevalence of migraine is higher in Europe than in Africa. Evolution is often accompanied by trade-offs among genetic traits, and the TRPM8 gene may represent one of the reasons why migraine susceptibility has been retained through natural selection.

Figure 1. An image from the literature shows that the frequency of this variant is as high as 88% in Finland (FIN; dark blue in the pie chart). In contrast, the frequency is much lower in African countries (yellow in the pie charts), at approximately 5%.

During my more than one year of training in Mayo Clinic, Rochester, Minnesota, USA, I often felt that people living at higher latitudes (Minnesota is the northernmost state in the U.S. after Alaska) differ from those living at lower latitudes. The most noticeable difference is during the cold winter: it is common to see people walking outside in short sleeves, including kindergarten children. In contrast, my daughter and I often found the cold unbearable. The difference is equally evident in summer (June to August), when local residents often find temperatures above 25°C difficult to tolerate and prefer to stay indoors with air conditioning.

After reading this genetic analysis, I began to think that perhaps each individual has an optimal temperature and environment suited for survival. This may also help explain why many ethnic Chinese individuals who have lived long-term in the United States choose to relocate to warmer regions, such as Southern California, after retirement.

I am grateful to Dr. Yi-Hsien Tu for compiling and sharing this literature.

心律不整會中風？ Cardiac Arrhythmia Cause a Stroke?

作者： 蔡昇達

過年前的一天晚上 11:55，外院轉診的急性腦中風患者抵達，正在評估中風嚴重度時，床尾突然有個熟悉的聲音叫我，「蔡醫師」。原來眼前的這位正是我之前門診照顧多年的患者，每次皆是兒子帶著她，開車近兩個小時前來，往事也漸漸浮現。

照片一，第一次中風的腦部影像，白色楕圓的區域即為中風的地方 (箭頭所指)

六年前患者第一次腦中風，在左腦皮質處，檢查發現有三高(糖尿病、高血壓、高血脂)，開始藥物治療，但影像的特徵和病人的症狀(時常心悸)，提醒著我可能是心房顫動(一種心律不整)造成的中風，但做了三張一次性的心電圖，及 24 小時心電圖，皆未發現心律不整，故以三高造成的中風治療，給予抗血小板藥物(Aspirin or Clopidogrel)。兩年前又發生一次中風，一樣未發現心律不整，這次又中風，嚴重度很高，不過兒子及女兒有了兩次的經驗，非常警覺，兒子送媽媽上床睡覺時覺得媽媽怎麼突然不動、不講話了，立刻知道又中風了，馬上送到急診室，醫師也立即施打了血栓溶解劑，轉到我們醫院，症狀已大幅改善，外院急診的心電圖見心房顫動、本院剛做完的 24 小時心電圖(執行原因：時常心悸)也證實為心房顫動。

這六年來我向兒子解釋時，時常會提到心律不整，並不定時安排心臟的檢查，這次跟他說明，「中風的兇手終於現形了，是心房顫動，一種心律不整」，兒子聽完後非常狐疑的問我，「心律不整會中風？」讓我頗為驚訝，這六年來兒子親力親為照顧媽媽，各種檢查、治療皆問得非常詳細，對中風的知識已接近醫療人員水準，但這項我跟他講了數年的概念，卻仍然無法了解，讓我知道這件事的複雜性，也決定寫下這篇文章。

簡單的說，當心臟發生心房顫動時，心臟上面的「心房」不再正常收縮，而是像在抖動，沒有真正把血擠出去，結果造成血流變慢、變亂，因而容易形成血栓 (古文說，戶樞不蠹，流水不腐)，而血栓跑出心臟，到達腦部血管，即造成栓塞性腦中風(embolic stroke)。而這種中風，所要吃的藥是不同的，抗血小板藥物(Aspirin, Clopidogrel, Cilostazol……等)是不足夠的，必須要升級至抗凝血藥物(Dabigatran, Rivaroxaban, Apixaban, Edoxaban, Warfarin……等)，而前任美國總統拜登，即是長期服用抗凝血藥，避免心房顫動造成栓塞性腦中風。

病歷整理完、向兒子說明完整，差不多時間要入住加護病房了，陪著患者搭電梯的時候，問了她一句，「記得我是誰嗎？」這時阿姨突然很清楚的跟我說，「你出國進修兩年，回來了，歡迎回來過年！」聽完很感動，感謝阿姨把我記住，也再次體會到血栓溶解劑的威力，可以讓嚴重的症狀很快改善、恢復正常。實在是相當棒的見面禮。

照片二，此次中風的腦部影像，白色的區域即為中風的地方 (箭頭所指)

English translation, with the help of Chat GPT 5

Title: Cardiac Arrhythmia Cause a Stroke?

Author: Sheng-Ta Tsai

One evening just before the Lunar New Year, at 11:55 p.m., a patient with acute ischemic stroke arrived after being transferred from another hospital. While I was assessing the severity of the stroke (The National Institutes of Health Stroke Scale, NIHSS), a familiar voice suddenly called out from the foot of the bed: “Dr. Tsai.” I immediately recognized him—she was a patient whom I had followed in the outpatient clinic for many years. Each time she visited, her son drove nearly two hours to bring her to the hospital. As I saw her again that night, many memories came back to me.

Figure 1. Brain imaging from the patient’s first stroke. The white oval region indicates the infarcted area (arrowhead).

Six years earlier, the patient had her first stroke, involving the left cerebral cortex. Examination revealed three major vascular risk factors—diabetes mellitus, hypertension, and hyperlipidemia—and medical treatment was initiated accordingly. However, both the imaging characteristics and the patient’s symptoms (frequent palpitations) suggested the possibility of atrial fibrillation, a type of cardiac arrhythmia that can lead to stroke. We performed three standard electrocardiograms as well as a 24-hour Holter monitor, but none detected any arrhythmia. Therefore, the stroke was treated as one related to vascular risk factors, and antiplatelet therapy (such as aspirin or clopidogrel) was prescribed.

Two years ago, she suffered another stroke. Again, no arrhythmia was detected. This time, however, the stroke was more severe. Fortunately, her son and daughter had gained experience from the previous events and were extremely vigilant. When her son helped his mother into bed that evening, he noticed that she suddenly stopped moving and speaking. Realizing that she might be having another stroke, he immediately took her to the emergency department. The emergency physician promptly administered thrombolytic therapy, and she was transferred to our hospital. By the time she arrived, her symptoms had already improved substantially. An electrocardiogram performed in the referring hospital’s emergency department revealed atrial fibrillation, and the 24-hour Holter monitoring we had just completed at our hospital (ordered because of her frequent palpitations) also confirmed atrial fibrillation.

Over the past six years, whenever I explained her condition to her son, I frequently mentioned the possibility of arrhythmia and arranged cardiac evaluations periodically. This time I told him, “The culprit behind the stroke has finally appeared—it is atrial fibrillation, a type of arrhythmia.” The son looked puzzled and asked, “Arrhythmia can cause stroke?” I was quite surprised. For six years he had devoted himself to caring for his mother, asking detailed questions about every examination and treatment. His understanding of stroke was almost at the level of a healthcare professional. Yet this concept—one that I had explained to him repeatedly over the years—remained difficult to grasp. At that moment I realized how complex this issue can be, which prompted me to write this article.

In simple terms, when atrial fibrillation occurs, the upper chambers of the heart—the atria—no longer contract normally. Instead, they quiver ineffectively and fail to pump blood efficiently. As a result, blood flow becomes sluggish and disorganized, which promotes the formation of blood clots (as an old saying suggests, “a moving hinge does not rust, and flowing water does not stagnate”). If such a clot travels out of the heart and reaches the blood vessels of the brain, it can block the vessel and cause an embolic stroke. The medications required to prevent this type of stroke are different. Antiplatelet agents (such as aspirin, clopidogrel, or cilostazol) are not sufficient; treatment must be escalated to anticoagulant therapy (such as dabigatran, rivaroxaban, apixaban, edoxaban, or warfarin). For example, former U.S. President Joe Biden has reportedly taken long-term anticoagulant therapy to prevent embolic stroke associated with asymptomatic atrial fibrillation.

After completing the medical documentation and explaining the situation thoroughly to her son, it was time for the patient to be admitted to the intensive care unit. While accompanying her in the elevator, I asked gently, “Do you remember who I am?” The patient suddenly replied clearly, “You went abroad for two years of training, and now you’re back—welcome home for the New Year!” I was deeply touched. I felt grateful that she still remembered me, and it reminded me once again of the remarkable effectiveness of thrombolytic therapy, which can rapidly improve even severe neurological symptoms and restore normal function. It was truly a wonderful reunion gift.

Figure 2. Brain imaging from the most recent stroke. The white area indicates the infarcted region (arrowhead).

妙佑醫療國際供應鏈 Mayo Clinic Supply Chain

 

作者： 蔡昇達

感謝 Mayo Clinic 的老闆 Dr. Kendall Lee，教我不僅要會看病、做研究，還要了解商業、世界運作的方式，安排了這次供應鏈的參訪。

一進到倉儲中心，除了巨大的空間和堆很高的各式物品外，最讓我印象深刻的是高掛的標語，「以病人為中心 (The Needs of the Patient Come First)」，這個信條著實貫徹在 Mayo 的每個角落。

各種各樣的物品，服務明尼蘇達及威斯康辛州 22 間的醫院、35 間的診所、總共九百多個配送點，Mayo Clinic 在佛羅里達及亞歷桑那的據點，也各服務兩百多個配送點，因為採購量大(超過七萬份的合約)，整個體系形成一個 Group Purchasing Organization (團體採購組織)，與供應廠商議價的能力極強，每年為 Mayo Clinic 節省大筆支出，盈餘做品質改善或是投入醫療服務，因此被評為全美前三名的醫療供應鏈： Mayo Clinic, Cleveland Clinic, Intermountain Healthcare (在猶他州)。舉 2019 年開始的新冠肺炎疫情為例，幾年下來整個 Mayo Clinic 體系並沒有發生「防護裝備不足」的狀況，在全美實屬難得。

機器人會看路徑上有沒有人或是其他機器人，自行閃避、調整路線。

整個供應鏈的管理 (Supply Chain Management, SCM)應用了許多資料分析和人工智慧的技術 (與 Amazon 的物流系統接近)，使用機器人之前，整個區域需安排 11 位工作人員，使用機器人後只需要在最重要的三個節點各安排一位，共三位工作人員，且使用後增進配送的效率為兩倍，另外，大幅減少了工作人員的職業傷害(如肌肉拉傷、扭傷等)。

每個機器人員工皆有名字，如上圖這個是參考星際大戰的天行者路克 (Luke Skywalker)。

機器人快沒電時會自己開回去上圖的充電區充電

這個妙佑醫療國際的物流中心，每週上班六天，每天皆是數十量大卡車進出，上面這張照片是「準備送出」的物品，一個區塊即是一輛車，大小車輛一天需送出至少 50 輛。

品管大螢幕，各個點代表不同的區域，如綠色的點表示那個區域物品配送流暢、效率高，管理者一眼即可知道哪邊出了狀況，需要前往關心。可以注意到，背後的標語也是醫院的核心精神：「The Needs of the Patient Come First」

原來在看病、開藥、手術的背後，有強大的後勤團隊在支援著，感恩為整個體系默默付出的人們！也感謝老闆的用心安排！

English version:

Author: Sheng-Ta Tsai

I am deeply grateful to my mentor at Mayo Clinic, Dr. Kendall Lee, for teaching me that being a good physician is not only about clinical care and research, but also about understanding business and how the world operates. He thoughtfully arranged this visit to Mayo Clinic’s supply chain operations.

Upon entering the inventory and distribution center, beyond the vast space and towering stacks of supplies, what impressed me most was the prominent slogan displayed overhead: “The Needs of the Patient Come First.” This core principle truly permeates every corner of Mayo Clinic.

A wide variety of supplies are managed here, serving 22 hospitals and 35 clinics across Minnesota and Wisconsin, with more than 900 delivery points in total. Mayo Clinic’s campuses in Florida and Arizona each support over 200 additional delivery locations.

Because of this massive purchasing volume, the system effectively functions as a Group Purchasing Organization (GPO), giving it strong bargaining power with suppliers. This results in substantial annual cost savings, which are reinvested into quality improvement initiatives and patient care services. As a result, Mayo Clinic is consistently ranked among the top three healthcare supply chains in the United States, alongside Cleveland Clinic and Intermountain Healthcare (based in Utah). Taking the COVID-19 pandemic that began in 2019 as an example, over the ensuing years the Mayo Clinic system did not experience shortages of personal protective equipment—a rare achievement across the United States.

Mayo Clinic’s Supply Chain Management (SCM) system incorporates extensive data analytics and artificial intelligence technologies—comparable in sophistication to Amazon’s logistics systems. In the video shown during the visit, robots autonomously transport supplies back and forth.

Before automation, this area required 11 staff members to operate. After implementation, only three staff members are needed—one at each of the three critical control points. This change has doubled delivery efficiency while also significantly reducing occupational injuries, such as muscle strains and sprains.

Each robotic “employee” even has a name. The robot shown in the photo above, for example, is named similar to Luke Skywalker from Star Wars.

This Mayo Clinic logistics center operates six days a week, with dozens of large trucks entering and leaving every day. The photo above shows items ready for shipment—each designated zone corresponds to a single truck. At least 50 trucks of various sizes are dispatched daily.

A large quality-control dashboard displays operational status across different zones. Each dot represents a specific area: green dots indicate smooth, efficient supply flow. At a glance, managers can immediately identify problem areas and intervene as needed.

It is only now that I truly appreciate that behind every clinic visit, prescription, and surgical procedure, there is a powerful logistics and support team working quietly in the background. I am deeply grateful to everyone who contributes to this system behind the scenes—and once again, thankful for my mentor’s thoughtful arrangement of this visit.

腸內菌與巴金森氏症及糖尿病 (Gut Microbiota, Parkinson’s Disease, and Diabetes)

 

作者： 蔡昇達

人們早早就知道腸子中的細菌對人的健康很重要，所以排便不順暢的大人或是小孩常會服用益生菌，近二十年來，醫師及科學家們從臨床的觀察：「巴金森氏症發病前十幾年，有相當高比例的人會有便祕的症狀」，接著由一系列的觀察性研究、介入性研究、動物實驗等，證實「腸-腦軸線(gut-brain axis)」的存在，即腸子中的細菌會經由代謝、基因等作用，影響腦部，而開啟了眾多的腸道菌研究，我個人覺得最清楚易懂的是下方的表格(出自盧森堡的團隊)，其中藍色格子代表「正常人比巴金森氏症病人還多的細菌」，紅色表示「巴金森氏症病人比正常人還多的細菌」： 

有趣的是益生菌常見之成份、我們喜歡的乳酸桿菌(Lactobacillaceae)，竟然很一致的顯示在巴金森氏症的病人較多！這啟發我的好奇心： 或許對於巴金森氏症的病人，補充益生菌並不一定有益處？之後做了許多文獻的搜索，也發現對於急性胰臟炎的病人，若補充含有乳酸桿菌及比菲德氏桿菌屬的益生菌(Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus salivarius, Lactococcus lactis, Bifidobacterium bifidum, and Bifidobacteriumlactis，Lancet 2008; 371: 651–59)，其死亡率較未補充益生菌者為高，亦有文章談到商業利益對科學研究與發表的影響(Faecal transplantation, Pro- and Prebiotics in Parkinson’s Disease; Hope or Hype?)，提醒科學家們謹慎看待。

2024 年法國團隊在新英格蘭醫學雜誌(NEJM)發表一篇重磅的研究，發現 Lixisenatide，一種 GLP1 agonist (糖尿病用藥)，可以減緩巴金森氏症動作症狀的惡化(Meissner WG, Remy P, Giordana C, Maltête D, Derkinderen P, Houéto J-L, et al. (2024). Trial of lixisenatide in early Parkinson’s disease. N Engl J Med, 390:1176-1185.)，表示此二重要疾病應有其關聯性，故中醫大神經內科與新陳代謝科陳主任合作，交叉比對，並篩選到屬及種(以前學的「界門綱目科屬種」)、並排除服用益生菌的病人，發現 Lactobacillus salivarius 及 genus Akkermansia 在巴金森氏症病人及糖尿病病人族群，均較健康人為多，或許可從一個角度推出巴金森氏症與糖尿病的關聯性，供後續的研究參考。(亦可參考本院出版的刊物： 中國醫訊 220 期第 19 頁)

此臨床研究很感謝計劃助理佳均、家甄、嘉嘉協助收案、建檔、簽同意書……等、感謝蔡崇豪院長及呂明桂主任協助收案，感謝檢驗部薛院長的指導、賴博、逸堯的資料分析、感謝已故的新陳代謝科陳清助主任的一同合作、感謝陳佳陽醫師幫忙收集臨床資料、感謝藝瀚、楊醫師在統計方面的協助、感謝 Mayo Clinic Marina 教授的合作分析，這篇文章經歷了四次的退稿，最後一次有位 reviewer 的評論亦相當嚴竣，感謝逸堯協助依 reviewer 的意見重做分析、展現高度的誠意，終被接受刊登，很高興與各位分享此研究，另外，建議您在補充益生菌前先詢問醫師的意見，或許補充益生菌不一定對您有好處。

本團隊發表在《科學報告》的全文如下：

Elevated Lactobacillus salivarius and genus Akkermansia in fecal samples of Taiwanese patients with Parkinson’s disease and diabetes mellitus

English version:

Title: Gut Microbiota, Parkinson’s Disease, and Diabetes

For centuries, people have recognized the importance of gut bacteria in maintaining health. Adults and children with constipation often take probiotics, reflecting a widespread belief that “good bacteria” support gastrointestinal function. Over the past two decades, however, clinical observations and biomedical research have extended this understanding far beyond digestion.

One key clinical observation is that more than ten years before the onset of Parkinson’s disease (PD), a substantial proportion of patients already exhibit chronic constipation. Subsequent observational studies, interventional trials, and animal experiments have confirmed the presence of the gut–brain axis—a bidirectional communication network through which gut microbes influence brain physiology through metabolic, genetic, and immunologic mechanisms. This has catalyzed an explosion of gut-microbiome research.

Among many studies, a 2018 investigation by a research team in Luxembourg produced what I consider one of the most intuitive summary tables. In their analysis, blue cells represent bacterial taxa more abundant in healthy individuals, while red cells represent taxa more abundant in patients with Parkinson’s disease.

The Surprising Role of Probiotics in Parkinson’s Disease

A particularly intriguing finding is that Lactobacillaceae—a family of bacteria commonly found in probiotic supplements and widely regarded as beneficial—appears consistently elevated in Parkinson’s disease patients. This led me to question whether probiotic supplementation is universally beneficial.

Further literature review uncovered additional concerns:

A landmark randomized trial in The Lancet (2008; 371:651–659) showed that patients with acute pancreatitis who received probiotics containing Lactobacillus acidophilus, L. casei, L. salivarius, Lactococcus lactis, Bifidobacterium bifidum, and B. lactis experienced higher mortality compared with those who did not receive probiotics. Other commentaries have also raised questions regarding commercial influence on probiotic research (e.g., Faecal transplantation, Pro- and Prebiotics in Parkinson’s Disease: Hope or Hype?), reminding scientists to remain cautious and critical.

New Evidence Linking Parkinson’s Disease and Diabetes

In 2024, a French research group published a groundbreaking trial in the New England Journal of Medicine, demonstrating that lixisenatide, a GLP-1 receptor agonist used in diabetes treatment, slows the progression of motor symptoms in early Parkinson’s disease:

Meissner WG, Remy P, Giordana C, Maltête D, Derkinderen P, Houéto J-L, et al. (2024). Trial of lixisenatide in early Parkinson’s disease. N Engl J Med, 390:1176–1185.

This finding suggests a mechanistic connection between diabetes and Parkinson’s disease.

In light of this, our neurology and endocrinology teams collaborated to analyze microbiome datasets. After cross-comparison, genus- and species-level filtering, and exclusion of patients taking probiotic supplements, we found that:

Lactobacillus salivarius, and Genus Akkermansia were elevated not only in Parkinson’s disease patients but also in patients with diabetes, compared with healthy controls. These shared microbial patterns provide a potential clue linking the two disorders, offering a valuable direction for future research.

Here is the link for our published article (on Scientific Reports): 

Elevated Lactobacillus salivarius and genus Akkermansia in fecal samples of Taiwanese patients with Parkinson’s disease and diabetes mellitus

Acknowledgments

This clinical study would not have been possible without the dedicated support of many colleagues. I am grateful to:

Project assistants Chia-Chun, Chia-Chen, and Chia-Chia for case enrollment, data entry, and consent procedures

Dean Chon-Haw Tsai and Director Ming-Kuei Lu for assistance with recruitment

Director Hsueh of the Laboratory Medicine Department for guidance

Dr. Lai and Yi-Yao for data analysis

The late Director Chen Ching-Chu (Endocrinology & Metabolism), whose collaboration and generosity made this study possible

Dr. Chen Chia-Yang for collecting clinical information

Dr. Yi-Han Hu and Dr. Chia-Chun Yang for statistical support

Professor Marina of Mayo Clinic for collaborative analyses

This manuscript went through four rounds of rejection, and the final reviewer’s critique was demanding. I am especially thankful to Yi-Yao, who re-analyzed the dataset in full alignment with the reviewer’s concerns. That rigorous effort demonstrated our sincerity and ultimately led to acceptance.

I am pleased to share these findings with you. Finally, I recommend consulting your physician before taking probiotic supplements—because, as research increasingly shows, probiotics may not always be beneficial for everyone.

秋末烏鴨 Late-Autumn Crows

作者： 蔡昇達

11/6(四)做了整天的實驗，下午開始天氣快速變冷，五點多時開車回家換厚外套，回實驗室時很高興的停在距離門口最近的樹下(難得有這麼近的空停車位)，想不到九點多做完實驗出來，整車竟然滿滿的皆是烏鴨大便！四個小時的時間，我得到了實驗數據，也得到了滿滿的鳥大便。

圖一、四小時累積的烏鴨大便

回來查了資料，原來明尼蘇達州羅徹斯特市的烏鴉問題已經困擾了幾十年，從 1980 年代就開始了。主要是天冷時城市較溫暖，吸引烏鴨群聚，且幼鳥已養育得差不多，成鳥有較多社交的行為……等，甚至因造成城市居民的困擾及健康風險，去年政府派出神槍手，用塑膠子彈驅趕烏鴨。

圖二、2024 年羅徹斯特市的新聞

過去一年半，我皆是自己洗車(想說美國人工太貴)，但此次實在太驚人，不得不到洗車場請人幫忙，沒想到比想像的便宜許多(含稅 11 美元)，且服務甚佳。洗車的年輕人還請我搖下車窗，問我到底是怎麼了？怎麼可以這麼誇張！

圖三、洗車時從車內拍出去的洗車廠內部

圖四、免費的超強力吸塵器，自助使用

解鎖了洗車服務，以後不必再辛苦的自己洗車、吸塵，為此次最大的收穫。感謝骨科學長介紹的洗車廠。

圖五、花 11 美元清掉滿滿的烏鴨大便，實在值得！

English version:

On Thursday, November 6, I spent the entire day running experiments. By afternoon, the weather had suddenly turned cold. Around five o’clock I drove home to change into a thicker coat. When I returned to the lab, I happily parked under the tree closest to the entrance — a rare empty spot that near!

Unexpectedly, when I finished my experiments and came out around nine o’clock, I found my entire car completely covered with crow droppings. In just four hours, I obtained both my experimental data and a car full of bird excrement.

After checking the internet, I discovered that the crow problem in Rochester, Minnesota, has actually troubled the city for decades — dating back to the 1980s. In winter, the city’s slightly warmer temperature attracts large gatherings of crows. By this season, the young have already been raised, and the adult birds engage in more social behaviors. The situation has caused such nuisance and potential health risks to residents that last year the government even sent sharpshooters armed with plastic bullets to drive the crows away.

For the past year and a half, I’ve always washed my car myself (labor costs in the U.S. are high, after all). But this time the mess was so extraordinary that I had no choice but to go to a car wash and ask for help. To my surprise, it was much cheaper than I expected — only $11 including tax — and the service was excellent.

One of the young workers even asked me to roll down my window and exclaimed, “I am curious what on earth happened? How could your car get this bad? I will get it off.”

By “unlocking” the car-wash service, I no longer need to struggle washing and vacuuming the car by myself — truly the greatest reward from this episode. Many thanks to my orthopedic senior colleague (Dr. Sam Chen) who recommended this car wash!

Lake Superior 蘇必略湖

作者： 蔡昇達

美國明尼蘇達州境內有許多湖，號稱「萬湖之州」，其中最大的為蘇必略湖(Lake Superior)，來到這邊一年多，終於有時間探訪這世界上面積最大的淡水湖。

日落時的蘇必略湖，紅藍混合的顏色很夢幻

五大湖的形成源於第四紀(Quaternary Period，距今約一萬年前)的巨大冰川(勞倫泰德冰蓋)往南移動時的冰蝕作用，因壓力造成地殼下沉，形成低漥的凹地，成為五大湖的基底，待氣候變暖時冰川融化，形成大型的淡水湖，其中最大的即為蘇必略湖。

1866 年，地質學家 Henry H. Eames 在明尼蘇達州北部發現豐富的高品質鐵礦，1891 年 Duluth, Missabe and Northern Railway (DM&N, DMN)鐵路公司成立，1892 年第一批鐵礦石通過此鐵路送到蘇必略湖畔的碼頭運出。(參考影片： Duluth, Missabe and Iron Range Railway, The Last Days - FULL VIDEO (2004))

紅色即表示在蘇必略湖附近發現的鐵礦(來自維基百科)，最主要的為 Mesabi (= Missabi) Range

最早運送鐵礦的 Duluth, Missabe and Iron Range Railway

Duluth 的秋景、鐵礦(在港口邊，放大才看得清楚)、及鐵路

1905 年 11 月底，繁忙的蘇必略湖風雪漸大，晚上時一艘貨船(Madeira 號)撞上岸邊礁石，許多人喪生，故幾年後在該地建造了燈塔，維護行船的安全，燈塔運行的數十年間，未再有貨船觸礁。

高聳峭壁上的燈塔 Split Rock Lighthouse，是全美排名很前面的熱門觀光燈塔

因北方的明尼蘇達州提供高品質的鐵礦、東部的阿帕拉契山脈（Appalachian Mountains）擁有豐富煤炭，加上五大湖的水運系統(如下照片)，使五大湖區成為理想的重工業帶，1920–1960年間，該區人口迅速增長，出現典型的工業城市，例如：底特律被稱為「汽車之都」，匹茲堡為「鋼鐵之城」，克里夫蘭為「機械之心」。

五大湖的通航路線圖，可以直接由最上游的蘇必略湖接到北大西洋

1970 年代後因海外低價鋼鐵與汽車競爭、高利率致美元升值……等因素，產業外移至美國南部或亞洲（如日本、韓國)、大量工廠關閉、失業率上升、城市人口外移，因而出現著名的「鐵鏽帶(Rust Belt)」，意思是曾經輝煌的重工業基地，如今設備生鏽、經濟停滯。

橘紅色為鐵鏽帶、灰色區為前面提到的煤炭產區(阿帕拉契山脈)
Source: Brendan H. Jennings--Saline County, Illinois, historian (2010).

不過 Lake Superior 附近的鐵礦至今仍持續開採中，且 Duluth 仍然為重要的港口、及觀光勝地，相當值得一訪。

Duluth 港出口處的 Aerial lift bridge，有船隻通過時即會升起

蘇必略湖北岸公路旁的 Gooseberry falls

Aerial lift bridge 夜景

而明尼蘇達州在 20 世紀後期經濟轉型，從農業與採礦業轉向服務業、金融與醫療保健，許多著名公司的總部皆在此，如 3M Health Care, Medtronic, UnitedHealth Group......等，當然還有最富盛名的 Mayo Clinic。明州在預期壽命、醫療水平與教育質量方面名列前茅，人均收入高於全美平均。

與合作的神外學長，陳醫師，在 Mayo 圖書館之梅約兄弟畫像前合照

English version:

Minnesota, known as the “Land of 10,000 Lakes,” is home to countless bodies of water, the largest of which is Lake Superior. Having lived here for more than a year, I finally found the time to visit this magnificent natural wonder — the largest freshwater lake by surface area in the world.

The formation of the Great Lakes dates back to the Quaternary Period (around ten thousand years ago), when the massive Laurentide Ice Sheet advanced southward. The glacier’s immense pressure eroded and depressed the Earth’s crust, carving out vast basins that later became the foundation of the Great Lakes. As the climate warmed and the glaciers melted, these basins filled with meltwater, forming a chain of immense freshwater lakes — among which Lake Superior is the largest.

In 1866, geologist Henry H. Eames discovered abundant high-grade iron ore in northern Minnesota. The Duluth, Missabe and Northern Railway (DM&N) was established in 1891, and by 1892, the first shipments of iron ore were transported by rail to the docks along Lake Superior for export.

(Reference video: “Duluth, Missabe and Iron Range Railway, The Last Days – FULL VIDEO (2004)”).

In late November 1905, a severe snowstorm struck busy Lake Superior. That night, the freighter Madeira crashed against the rocky shore, resulting in heavy loss of life. In response, a lighthouse was later built at the site to ensure maritime safety. During the many decades the lighthouse operated, no shipwrecks occurred in that area again.

Because northern Minnesota supplied high-quality iron ore, the Appalachian Mountains in the east provided abundant coal, and the Great Lakes offered an efficient inland waterway system (as shown in the photo below), the region became an ideal location for heavy industry. Between 1920 and 1960, the population of the Great Lakes area surged, and numerous industrial cities emerged: Detroit became known as the “Motor City,” Pittsburgh as the “Steel City,” and Cleveland as the “Heart of Machinery.”

However, after the 1970s, competition from low-cost foreign steel and automobiles, together with high interest rates and the rising value of the U.S. dollar, led to industrial decline. Many factories relocated to the southern United States or overseas (such as Japan and South Korea), resulting in widespread plant closures, soaring unemployment, and urban depopulation. This transformation gave rise to the so-called “Rust Belt,” referring to once-prosperous industrial centers now characterized by rusting facilities and economic stagnation.

Nevertheless, iron mining near Lake Superior continues today, and Duluth remains both an important port and a popular tourist destination — well worth a visit.

In the latter half of the 20th century, Minnesota underwent an economic transformation, shifting from agriculture and mining to service industries, finance, and healthcare. Many renowned companies are headquartered here, such as 3M Health Care, Medtronic, and UnitedHealth Group… and of course, the most prestigious of all, the Mayo Clinic. Minnesota ranks among the top in life expectancy, healthcare standards, and education quality, with a per capita income above the national average.