Clavicle(left)

Clavicle

spinoglenoid notch

(suprascapular notch)

(intertubercular sulcus)

obique line

Ulnar(left?)

(Palmar view of left hand)

carpal arch(tunnel)

tubercle of the crest

posterior

anterior gluteal line

inferior

感覺iliopubic eminence在pubis?

Greater Sciatic Notch

Ischium

lesser sciatic notch

Acetabular Fossa

Acetabular Notch

pubis(medial view)

pubic symphisis

iliopubic eminence?

quadrate tubercle

malleolar fossa

intercondylar eminence

styloid process

Tarsal Bones

Sutures

(Bregma)

(Lambda)

External

Lateral

Frankfurt Plane

(zygomatic arch)

styloid process

Anterior

infraorbital foramen

Mandible

lingula

mylohyoid line

mylohyoid groove

Inferior

hard palate

(intermaxillary suture)

incisive fossa(canals inside)

-pterygoid plate(medial, lateral)

pterygoid fossa

greater palatine fpramina

lesserer palatine fpramina

pterygoid hamulus

mandibular fossa

carotid canal

jugular foramen

Pharyngotympanic tube (auditory tube)

stylomastoid foramen

hypoglossal canal

cranial cavity roof

groove for SSS

frontal crest

cranial cavity floor

anterior clinoid process

tuberculum sellae(middle clinoid process)

hypophyseal fossa

dorsum sellae(posterior clinoid process)

clivus

crista galli

Questions

1. 根據病患抽血結果，請問病患較屬於哪一類型休克？

2. 休克復甦(resuscitation)時要注意哪些狀況？是否會併發其他器官功能異常，及其背後病理機轉為何？

抽血檢驗項目簡簡介

RBC: RBC concentration

HB: Hemoglobin concentration

HCT:  volume percentage of RBC in blood

抽血檢驗項目簡簡介

MCV (mean corpuscular volume): $\frac{HCT}{RBC}$, average volume of RBC

MCHC(mean corpuscular hemoglobin concentration): $\frac{HB}{HCT}$, average concentration of hemoglobin in RBC 

抽血檢驗項目簡簡介

PLT:  platelet concentration

RDW-CV: range of variation of RBC size

WBC: WBC concentration

抽血檢驗項目簡簡介

AST(GOT)/ALT(GPT): indicators of liver inflammation

抽血檢驗項目簡簡介

BUN(blood urea nitrogen)/Cre(creatinine): indicators of kidney health

抽血檢驗項目簡簡介

Lactic acid: increases due to hypoxia or impaired renal/hepatic function

hsCRP(high sensitivity-C reactive protein): a inflammation marker

Blood Test Results in Shocks

Blood Test Results in Shocks

• increased lactic acid $\implies$ shock(hypoxia)
• increased BUN, Cre, ALT, AST$\implies$end-organ dysfunction related to shock
• increased WBC, left swift$\implies$ infection?
• decreased hemoglobin and hematocrit$\implies$hemorrhagic hypovolemic shock

What kind of shock?

A. Distributive Shock

B. Cardiogenic Shock

C. Hypovolemic Shock

D. Obstructive Shock

What kind of shock?

A. Distributive Shock

B. Cardiogenic Shock

C. Hypovolemic Shock       (with infection?)

D. Obstructive Shock

Questions

1. 根據病患抽血結果，請問病患較屬於哪一類型休克？

2. 休克復甦(resuscitation)時要注意哪些狀況？是否會併發其他器官功能異常，及其背後病理機轉為何？

Complications of Fluid Resuscitation

• Coagulation Disorders
• Reperfusion-Mediated Injury
• Pulmonary Edema/ARDS

Coagulation Disorders

H.P. Pham, B.H. Shaz,Update on massive transfusion,British Journal of Anaesthesia,Volume 111, Supplement 1, 2013

Reperfusion-Mediated Injury

H.P. Pham, B.H. Shaz,Update on massive transfusion,British Journal of Anaesthesia,Volume 111, Supplement 1, 2013

• Cause general tissue injury/dysfunction

Oxygen-Derived ROS

$\implies$

plasma membrane damage

Cytokines(IL-1,IL-6,IL-8,TNF-$\alpha$)

neutrophil activation

More ROS

Acute Respiratory Distress Syndrome

pulmonary edema

Lee J, Corl K, Levy MM. Fluid Therapy and Acute Respiratory Distress Syndrome. Crit Care Clin. 2021 Oct

ARDS

pulmonary edema

shock/inflammation

increased vascular permeability

fluid resuscitation

increased hydrostatic pressure

Other References

[1]Fluid Resuscitation: State of the Science for Treating Combat Casualties and Civilian Injuries. Institute of Medicine (US) Committee on Fluid Resuscitation for Combat Casualties; Pope A, French G, Longnecker DE National Academies Press (US); 1999.

[2]Huppert LA, Matthay MA, Ware LB. Pathogenesis of Acute Respiratory Distress Syndrome. Semin Respir Crit Care Med. 2019

不太考

不太考

應該會考

(plasma cell)

2. epithelial infoldings and papilla

不太考

不太考

(or lymph node)

4. maturation with descent

3. invaginated respiratory epithelium with cystic dilation

不太考

不太考

3. Dilation of central vein

 (maybe with organization)

(including glomerulus)

可能跟ulcer一起

(可以寫多一些)

Question

4. 呼吸道病毒感染後常見的細菌感染有哪些？初步的痰液染色如下圖，如何描述以及最可能的致病菌是什麼？

Common Secondary Bacterial Infections Associated to Viral Respiratory Tract Infections

• Streptococcus pneumoniae
• Staphylococcus aureus
• Haemophilus influenzae
• Pseudomonas Aeruginosa

Manna S, Baindara P, Mandal SM. Molecular pathogenesis of secondary bacterial infection associated to viral infections including SARS-CoV-2. J Infect Public Health. 2020

Common Secondary Bacterial Infections Associated to COVID-19

Hugh C. Murray, Michael Muleme, Darcie Cooper, Bridgette J. McNamara, Mohammad A. Hussain, Caroline Bartolo, Daniel P. O'Brien, Eugene Athan, Prevalence, risk factors, and outcomes of secondary infections among hospitalized patients with COVID-19 or post–COVID-19 conditions in Victoria, 2020-2023, International Journal of Infectious Diseases,2024

n = 194,660

How do secondary bacterial infections happen?

Bosch AA, Biesbroek G, Trzcinski K, Sanders EA, Bogaert D. Viral and bacterial interactions in the upper respiratory tract. PLoS Pathog. 2013

NA:neuraminidase

SA: sialic acid

How do secondary bacterial infections happen?

Bosch AA, Biesbroek G, Trzcinski K, Sanders EA, Bogaert D. Viral and bacterial interactions in the upper respiratory tract. PLoS Pathog. 2013

Those Pathogens in Sputum

S. pneumoniae (Gram-positive lancet-shaped diplococci)

S. aureus (Gram-positive cocci in clusters)

Fukuyama H, Yamashiro S, Kinjo K, Tamaki H, Kishaba T. Validation of sputum Gram stain for treatment of community-acquired pneumonia and healthcare-associated pneumonia: a prospective observational study. BMC Infect Dis. 2014

Those Pathogens in Sputum

K. pneumoniae

 (Gram-negative rods large sized)

Fukuyama H, Yamashiro S, Kinjo K, Tamaki H, Kishaba T. Validation of sputum Gram stain for treatment of community-acquired pneumonia and healthcare-associated pneumonia: a prospective observational study. BMC Infect Dis. 2014

P. aeruginosa 

(Gram-negative rods small sized )

Those Pathogens in Sputum

?

Fukuyama H, Yamashiro S, Kinjo K, Tamaki H, Kishaba T. Validation of sputum Gram stain for treatment of community-acquired pneumonia and healthcare-associated pneumonia: a prospective observational study. BMC Infect Dis. 2014

H. influenzae 

(Gram-negative coccobacilli )

H. influenzae 

K. pneumoniae

P. aeruginosa 

S. pneumoniae 

S. aureus 

呼吸道病毒感染後常見的細菌感染有哪些？Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa

初步的痰液染色如下圖，如何描述以及最可能的致病菌是什麼？

S. aureus (Gram-positive cocci in clusters)

Question

6. 年長者或免疫不全病患建議的呼吸道相關疾病疫苗有哪些？

Vaccines for Respiratory Tract Infections

• Influenza Vaccine
• DTap Vaccine(tetanus, diphtheria, and pertussis)
• Pneumococcal Vaccine
• (Recombinant) Zoster Vaccine
• COVID-19
• RSV Vaccine

References:

Vaccines for Respiratory Tract Infections

• Influenza Vaccine
  • Getting a flu vaccine is now more important than ever as patients are at higher risk of serious COVID-19 health outcomes.
• DTap Vaccine(tetanus, diphtheria, and pertussis)
• Pneumococcal Vaccine
• (Recombinant) Zoster Vaccine
• COVID-19
• RSV Vaccine

Vaccines for Respiratory Tract Infections

• Influenza Vaccine
• DTap Vaccine(tetanus, diphtheria, and pertussis)
  • You should not miss an opportunity to vaccinate persons aged 65 years or older with Tdap. (CDC)
  • 19歲以上，十年打一次(CDC)
• Pneumococcal Vaccine
• (Recombinant) Zoster Vaccine
• COVID-19
• RSV Vaccine

Vaccines for Respiratory Tract Infections

• Influenza Vaccine
• DTap Vaccine(tetanus, diphtheria, and pertussis)
• Pneumococcal Vaccine
  • recommended for all adults 65 years or older
• (Recombinant) Zoster Vaccine
• COVID-19
• RSV Vaccine

Vaccines for Respiratory Tract Infections

• Influenza Vaccine
• DTap Vaccine(tetanus, diphtheria, and pertussis)
• Pneumococcal Vaccine
• (Recombinant) Zoster Vaccine
  • Recommended for adults 50 years or older
  • Varicella Pneumonia (rare)
  • Hospitalized patients with HIV or AIDS with chickenpox are at high risk for developing varicella pneumonia.(7/12)
• COVID-19
• RSV Vaccine

Popara M, Pendle S, Sacks L, Smego RA, Mer M. Varicella pneumonia in patients with HIV/AIDS. Int J Infect Dis 2002;6:6–8

Vaccines for Respiratory Tract Infections

• Influenza Vaccine
• DTap Vaccine(tetanus, diphtheria, and pertussis)
• Pneumococcal Vaccine
• (Recombinant) Zoster Vaccine
• COVID-19
  • Recommended for everyone (CDC)
• RSV Vaccine

Vaccines for Respiratory Tract Infections

• Influenza Vaccine
• DTap Vaccine(tetanus, diphtheria, and pertussis)
• Pneumococcal Vaccine
• (Recombinant) Zoster Vaccine
• COVID-19
• RSV Vaccine
  • Recommended for everyone who ages 75 and older/ages 60-74 who are at increased risk of severe RSV disease. (CDC)

Vaccines for Respiratory Tract Infections

Vaccines for Respiratory Tract Infections

Live vaccines might be contra-indicated in immunocompromised patients!

• BCG Vaccine(卡介苗): always contraindicated
• Varicella-containing Vaccines: contraindicated in people who are significantly immunocompromised as a result of a medical condition

Q(A)/Discussion

Physiology or Medicine

Physics

Chemistry

Literature

Peace

Economic Science

Physiology or Medicine Prize

Before Their Research

(lf)/lin-14(gf)

(lf)

[reiterated L1 stage growth]

[lack of L1 stage growth]

Victor Ambros

Gary Ruvkun

John Hopfield: Hopfield Network

A network of "neurons" with memory.

$\sum\limits_{V_j = 1, j \neq i} T_{ij}$

$\sum\limits_{V_j = 1, j \neq i} T_{ij}$

Geoffrey Hinton: Boltzmann Machine

An early generative model.

Pretty much like the Hopfield Network, but...

amino acid sequence

protein structure

David Baker: Rosetta Algorithm

A useful tool for structure prediction and protein design.

(published in 2004)

Foldit

Demis Hassabis, John Jumper: Alphafold

A deep learning model that "solves the 50-year-old grand challenge in biology".

散文

• Born 1970 in a literary family
• Devoted to art and music
• Suffers from migraine

偏頭痛

Some Novels of Han Kang(韓江)

• The Vegetarian, 2007(素食者)
• Human Acts, 2014(少年來了)
• The White Book, 2016(白)
• We do not part, 2021(不做告別)

NIHON HIDANKYO

(日本原水爆被害者団体協議会,日本被団協)

• Founded in 1956
• Composed of Hibakusya(被爆者, atomic bomb survivors)
• Objectives
  • Prevention of nuclear war and the elimination of nuclear weapons
  • State compensation for the atomic bomb damages
  • Improvement of the current policies and measures on the protection and assistance for the Hibakusya

制度

繁榮

Reversal of Fortune?

1500

Richer regions

Densely populated

Less settlers

Extractive institutions

colonized

High tax

discourage investment

1995

Poorer countries

Poorer regions

Sparsely populated

More Settlers
Institutions of private property

More incentive for investment

better economic performance

Richer countries

Want to know more?

• Try out the Hopfield Network Simulator
• Play Foldit
• Read one of Han Kang's novels
• Take a look at nobelprize.org

Additional References

(heart, other organs)

描述位置！

(may have heterologous elements, like cartilage or skeletal mescle)

Tumor Description:

1. border(infiltrative到哪裡/circumscribed/capsule)

2. architecture

3. cell 長相

4. stroma

5. 其他周邊異常

5. stromal desmoplasia

(Nabothian cyst)

(apoptosis/prominent nucleoli)

4. abrupt transition, depletion of goblet cell

(nuclear pleomorphism)

(elongated, tapered)

(cobweb structure)

localized type: circumscribed

(maybe cavernous or capillary)

(tadpole, spider cell)

(cambium layer?)-TSC

(pagetoid spread)

(hyperchromatic也可)

(只考在這)

(Gamna-Gandy body)

(HAM)

irregular lumen narrowing/intima thickening

Question

4. 周邊動脈疾病的治療有哪些?對胡先生的周邊動脈疾病，在藥物治療上如何調整?

Treatment for PAD

• Lifestyle Modification
• Structured Exercise
• Medication
• Intervention/Surgery

2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Treatment for PAD

• Lifestyle Modification
  • Smoking cessation
• Structured Exercise
• Medication
• Intervention/Surgery

2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Treatment for PAD

• Lifestyle Modification
• Supervised exercise program
  • For patients with claudication
  • Intermittent walking
  • At least 30–45 min/session; 3 times/wk for 12 wk
• Medication
• Intervention/Surgery

2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Medication for PAD

• Antiplatelet therapy(Aspirin or Clopidogrel)
  • reduce MI, stroke, and vascular death
• Statin
  •  improves both cardiovascular and limb outcomes
• Antihypertensive therapy (patients with hypertension)
  • reduce the risk of MI, stroke, heart failure, and cardiovascular death
• Cilostazol: Improve claudication symptoms
• Management of diabetes mellitus (patients with DM)
• Heparin for Anticoagulation (acute limb ischemia)

2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Intervention/Surgery for PAD (CLI)

• Revascularization
  • Endovascular/Surgical
• Amputation
  • should be performed as the first procedure in patients with a nonsalvageable limb

2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

胡先生藥物治療上如何調整？

• 感覺該吃的都吃了？
• The other drugs (Pentoxifylline, Procaterol, Acetylcysteine) are also not contradicted in PAD?
• Atorvastatin for PAD pateint: standard dose is 80 mg/day.

Sofat S, Chen X, Chowdhury MM, Coughlin PA. Effects of Statin Therapy and Dose on Cardiovascular and Limb Outcomes in Peripheral Arterial Disease: A Systematic Review and Meta-analysis. Eur J Vasc Endovasc Surg. 2021 Sep;62(3):450-461. doi: 10.1016/j.ejvs.2021.05.025. Epub 2021 Aug 10. PMID: 34389230.

Q(A)/Discussion

Question

5. 何謂急性後期照護?胡先生是否符合健保署的「急性後期整合照護計畫」的收案標準?是否有其他出院後照護的選擇?

急性後期照護(Post-Acute Care)

林純聿、周怡君：衰弱高齡患者的急性後期照護。內科學誌。2019：30：7-13。

• 「對醫療狀況相對穩定、但仍有特殊照顧需求的病患提供周全的住院後照顧」
• 銜接急性醫療與較低強度之照護
• 重視功能

急性後期照護(Post-Acute Care)

健保署 全民健康保險急性後期整合照護計畫

Question

5. 何謂急性後期照護?胡先生是否符合健保署的「急性後期整合照護計畫」的收案標準?是否有其他出院後照護的選擇?

急性後期整合照護計畫

健保署 全民健康保險急性後期整合照護計畫

• 計畫推動範圍包含腦中風、燒燙傷、創傷性神經損傷、脆弱性骨折、心臟衰竭、衰弱高齡病患

心臟衰竭？

健保署 全民健康保險急性後期整合照護計畫

心臟衰竭？

衰弱高齡？

衰弱高齡？

健保署 全民健康保險急性後期整合照護計畫

Question

5. 何謂急性後期照護?胡先生是否符合健保署的「急性後期整合照護計畫」的收案標準?是否有其他出院後照護的選擇?

出院後照護選擇

• 居家照顧
• 日間照護中心
• 長期照護機構

Q(A)/Discussion

Question

1. 以這位病人的入院診斷為例，如果你遇到一個病人肝硬化，你會再詢問他哪些病史，多做哪些理學檢查、實驗室診斷及影像學檢查，以進一步協助你做鑑別診斷，去判斷這位病人肝硬化的原因？肝硬化的成因有哪些？

Liver Cirrhosis: Etiology

Harrison's Principles of Internal Medicine, 21st Edition

Liver Cirrhosis: Differential Diagnosis

• History Taking
  • Alcohol Use
  • Travel, Sexual behaviors, Drug use 
  • Diabetes or Metabolic Syndrome
  • Autoimmune Disorder
  • Inflammatory Bowel Disease
    • Primary sclerosing cholangitis
  • Family History of Cirrhosis
  • Congestive Heart Failure
  • Anemia

Liver Cirrhosis: Differential Diagnosis

• Liver Function Tests
  • AST, ALT: Hepatocyte Injury
  • ALP, GGT: Cholestasis
  • Alcohol: AST>ALT, high GGT

Liver Cirrhosis: Differential Diagnosis

• Other Laboratory Tests

https://cirrhosiscare.ca/cirrhosis-provider/work-up-the-etiology/

https://en.wikipedia.org/wiki/Mallory_body

Alcoholic Hepatitis/NAFLD

https://www.pathologyoutlines.com/topic/liverautoimmune.html

AIH

PSC

https://pubs.rsna.org/doi/epdf/10.1148/rg.2019180213

https://www.aasld.org/liver-fellow-network/core-series/pathology-pearls/pathology-pearls-post-8-primary-sclerosing

Q(A)/Discussion

Question

2. 請問腹水的成因如何？如何解釋她腹水檢驗的結果？

Ascites: Cause

Harrison's Principles of Internal Medicine, 21st Edition

Why does Cirrhosis cause Ascites?

Harrison's Principles of Internal Medicine, 21st Edition

(RAAS, sympathetic)

serum-ascites albumin gradient (SAAG)

• SAAG: serum albumin - ascitic albumin
• SAAG >= 1.1 g/dL: Ascites caused by portal hypertension
  • ​Cirrhosis: ascitic protein < 2.5 g/dL
• SAAG < 1.1 g/dl: Other causes (TB, carcinomatosis, pancreatitis, ...)

Spontaneous Bacterial Peritonitis (SBP)

• In hospitalized patients with cirrhosis and ascites, SBP can occur in up to 30% of individuals. (Harrison)
  • ​Rare in patients without cirrhosis.
• ​Pathophysiology: Bacterial Translocation​

  • intestinal bacterial overgrowth, alterations of the intestinal mucosal barrier, deficiencies of the local immune response

  • Common Pathogen: E. coli, Klebsiella, Streptococcus

• Diagnosis
  • ​Ascitic PMN(neutrophils) >= 250/$\mu L$
  • Positive culture result
  • Absence of secondary causes of peritonitis

Harrison's Principles of Internal Medicine, 21st Edition

Spontaneous Bacterial Peritonitis: Pathogenesis, Diagnosis, Treatment. Florin Alexandru Cãruntu , Loredana Benea, 2006

Ascitic Fluid Analysis

• Lymphocyte Predominant: TB
• Lipase/Amylase: pancreatic damage
  • amylase > 1000 or 5x serum concentration
• Cytology: Malignancy
• RBC: 
  • High RBC: malignancy, trauma
  • Substract 1 neutrophil/750 RBC

Conclusion?

The patient's ascites and SBP are complications of liver cirrhosis, where the SBP might contribute to the development of ascites.

Question

1. 你是幫林小姐看診的消化內科醫師，請問你會如何跟林小姐解釋她眾多的消化系統問題，及建議她後續接受何種治療呢?

Steatohepatitis

"脂肪在肝臟過度堆積，並且肝臟發炎"

• Metabolic dysfunction-Associated Steatohepatitis?
  • No alcohol drinking
  • Obesity, DM, hyperlipidemia
• Treatment:
  • Hepatitis A,B vaccination, avoid alcohol
  • lipid-lowering therapy, blood glucose control
  • Weight loss
    • diet, excercise
    • bariatric surgery, drugs if goal not acheived after 6 months
  • Many drugs in development

UpToDate, Management of metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease) in adults

https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease

https://www.nejm.org/doi/full/10.1056/NEJMoa2309000

Gallstones

"膽囊中有結石"

• Treatment
  • Most do not require treatment if asymptomatic
  • Prophylactic cholecystectomy in selected patients
    • ​Increased risk of gallbladder cancer
      • Stone > 3 cm
      • Gallbladder Adenoma
      • ...
    • Hemolytic disorders

UpToDate, Approach to the management of gallstones

GERD

"胃酸從胃跑到食道，食道因此有發炎及黏膜受損"

https://www.grepmed.com/images/13202/egd-losangeles-esophagitis-diagnosis-grading

GERD

• Treatment:
  • Weight loss
  • Drugs
    • Proton Pump Inhibitors(PPI)
  • Lifestyle modification
    • Avoiding meals within 2–3 hours of bedtime
    • Avoid Trigger Foods
    • ...

Katz, Philip O. MD, MACG1; Dunbar, Kerry B. MD, PhD2,3; Schnoll-Sussman, Felice H. MD, FACG1; Greer, Katarina B. MD, MS, FACG4; Yadlapati, Rena MD, MSHS5; Spechler, Stuart Jon MD, FACG6,7. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. The American Journal of Gastroenterology 117(1):p 27-56, January 2022. | DOI: 10.14309/ajg.0000000000001538 

Colorectal Polyp

• Treatment:
  • Remove by  colonoscopy or surgery

"大腸長了良性的腫瘤，其中有些可能有機會發展成大腸癌"

"為什麼我的身體會有這些問題？"

"可能跟肥胖有關"

Camilleri M, Malhi H, Acosta A. Gastrointestinal Complications of Obesity. Gastroenterology. 2017 May;152(7):1656-1670. doi: 10.1053/j.gastro.2016.12.052. Epub 2017 Feb 10. PMID: 28192107; PMCID: PMC5609829.

OR:1.94

OR:1.87

OR:1.44

RR:4.66

RR

M: 2.51

F: 2.32

Colorectal polyp/CRC

Mechanisms?

GERD

Lagergren, J. Influence of obesity on the risk of esophageal disorders. Nat Rev Gastroenterol Hepatol 8, 340–347 (2011). https://doi.org/10.1038/nrgastro.2011.73

Bardou M, Barkun AN, Martel M. Obesity and colorectal cancer. Gut. 2013 Jun;62(6):933-47. doi: 10.1136/gutjnl-2013-304701. Epub 2013 Mar 12. PMID: 23481261.

Q(A)/Discussion

Question

3. 什麼是傾倒症候群? 發生的原因為何? 要如何預防和治療? 和術後血糖的改善有關嗎?

Dumping Syndrome 傾倒(ㄉㄠˋ?)症候群

a complication of bariatric surgery

symptoms

abdominal pain, nausea, diarrhea

fatigue, the need to lie down after meals, tachycardia, flushing

hypoglycemia

(palpitaion, fatigue, sweating, ...)

Alexandre Nuzzo, Sebastien Czernichow, Alexandre Hertig, Séverine Ledoux, Tigran Poghosyan, Didier Quilliot, Maude Le Gall, André Bado, Francisca Joly. Prevention and treatment of nutritional complications after bariatric surgery. Lancet Gastroenterol Hepatol. 2021 Mar;6(3):238-251. doi: 10.1016/S2468-1253(20)30331-9.

(Postbariatric Surgery Hypoglycemia)

Pathophysiology

Alexandre Nuzzo, Sebastien Czernichow, Alexandre Hertig, Séverine Ledoux, Tigran Poghosyan, Didier Quilliot, Maude Le Gall, André Bado, Francisca Joly. Prevention and treatment of nutritional complications after bariatric surgery. Lancet Gastroenterol Hepatol. 2021 Mar;6(3):238-251. doi: 10.1016/S2468-1253(20)30331-9.

Scarpellini, E., Arts, J., Karamanolis, G. et al. International consensus on the diagnosis and management of dumping syndrome. Nat Rev Endocrinol 16, 448–466 (2020). https://doi.org/10.1038/s41574-020-0357-5

• fluid shift in small intestine

VIP

GIP

GLP-1

• hypovolemia

GLP-1

Treatment: Diet
Similar for early/late dumping syndromes

• Small, frequent meals
• Liquids should be withheld until 30 minutes after the meal
• Avoid simple sugar and milk products
• Low GI, fiber-rich food
• Adequate protein intake

Hui C, Bauza GJ. Dumping Syndrome. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470542/

Treatment: Octreotide
a somatostatin analog

• inhibit secretion of insulin, glucagon, gastrin, secretin, VIP,...
• reduce secretion of fluids by the intestine and pancreas
• reduce gastrointestinal motility

Hui C, Bauza GJ. Dumping Syndrome. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470542/

Treatment: Acarbose
$\alpha$-glucosidase inhibitor

Rosak C, Mertes G. Critical evaluation of the role of acarbose in the treatment of diabetes: patient considerations. Diabetes Metab Syndr Obes. 2012;5:357-67. doi: 10.2147/DMSO.S28340. Epub 2012 Oct 12. PMID: 23093911; PMCID: PMC3476372.

Cadegiani FA, Silva OS. Acarbose promotes remission of both early and late dumping syndromes in post-bariatric patients. Diabetes Metab Syndr Obes. 2016 Dec 7;9:443-446. doi: 10.2147/DMSO.S123244. PMID: 27994477; PMCID: PMC5153290.

Question

3. 什麼是傾倒症候群? 發生的原因為何? 要如何預防和治療? 和術後血糖的改善有關嗎?

Glucose Metabolism After bariatric surgery

Q(A)/Discussion

(or solid/micropapillary)

(                    )

(keratin pearl/intercellular bridges)

在氣管旁要找，有要寫

(multinucleated giant cell)

lung

(may have necrosis)

(may have exudate)

(難出)

(page)!!!

(plasma cell看到要寫)

不高機率考

(DIPCF)

PPOD

可能沒有！

(USRP)

(TING)

[                                           ]    

may have granulation tissue

(PACCF)

may have autolysis/fat necrosis

(plasma cell)

sulfur granules: actinomycosis

mucormycosis: aspeptate hyphae with wide-angle branching

aspergillosis: fungal hyphae with septa  and acute angle branching

candidiasis: fungal yeasts and pseudohyphae

5. stromal desmoplasia

skin?

(POV)

問題一：良性攝護腺增生引起的下泌尿道症狀(low urinary tract symptom, LUTS)有哪些?有哪些藥物可治療，治療機轉為何?

LUTS (Low Urinary Tract Symptoms)

Scher HI, Eastham JA. Benign and Malignant Diseases of the Prostate. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J. eds. Harrison's Principles of Internal Medicine, 21e. McGraw-Hill Education; 2022. Accessed February 26, 2025. https://accessmedicine.mhmedical.com/content.aspx?bookid=3095&sectionid=263547112

IPSS

Mirone V, Imbimbo C, Longo N, Fusco F. The detrusor muscle: an innocent victim of bladder outlet obstruction. Eur Urol. 2007 Jan;51(1):57-66. doi: 10.1016/j.eururo.2006.07.050. Epub 2006 Aug 14. PMID: 16979287.

Detrusor muscle of bladder

問題一：良性攝護腺增生引起的下泌尿道症狀(low urinary tract symptom, LUTS)有哪些?有哪些藥物可治療，治療機轉為何?

Medical Treatment of BPH

• Goal: Relief symptoms
• Drugs
  • $\alpha1$-adrenergic receptor antagonist
    • Terazosin, Doxazosin, Alfuzosin, Tamsulosin, Silodosin
  • $5\alpha$-reductase inhibitor (5ARI)
    • Finasteride, Dutasteride
  • phosphodiesterase-5 (PDE5) inhibitor
    • ​Tadalafil
  • anticholinergics (controversial)
    • ​Tolterodine, Oxybutynin

Mechanisms of Action

Testosterone

DHT

(only for irritative symptoms)

Showalter, V.C., Raynor, M.C. (2020). Medical Management of Benign Prostatic Hyperplasia. In: Isaacson, A., Bagla, S., Raynor, M., Yu, H. (eds) Prostatic Artery Embolization. Springer, Cham. https://doi.org/10.1007/978-3-030-23471-3_3

??

PDE5 inhibitor?

Cellek, S., Cameron, N., Cotter, M. et al. Microvascular dysfunction and efficacy of PDE5 inhibitors in BPH–LUTS. Nat Rev Urol 11, 231–241 (2014). https://doi.org/10.1038/nrurol.2014.53

PDE5 inhibitor?

Cellek, S., Cameron, N., Cotter, M. et al. Microvascular dysfunction and efficacy of PDE5 inhibitors in BPH–LUTS. Nat Rev Urol 11, 231–241 (2014). https://doi.org/10.1038/nrurol.2014.53

Q(A)/Discussion

Chronic Kidney Disease: Epidemiology

Chronic Kidney Failure: Epidemiology

• More than 808,000 people in the United States are living with kidney failure
• Medicare-related spending for kidney failure totaled $52.3 billion in 2021

Chronic Kidney Failure: How to Treat?

Two options!

• Dialysis
• Kidney Transplant

Where are the kidneys from?

•  Deceased donors
  • Only a tiny fraction of deaths allow kidneys to be recovered for transplantation.
• Living donors
  • Who would like to give you his/her kidney?

Living Donors

• Non-Directed Donation
  • A person can choose to donate a kidney to an unknown recipient.
  • HARD: It's illegal to pay a living donor to donate a kidney, so there's little incentive.
•  Directed Donation
  • In the U.S., the donor can be the recipient's relative or friend.
  • HARD: Incompatibility.

Compatibility

ABO Compatibility

Tissue Type Compatibility

Kidney Exchange!

Kidney Exchange!

Donor

Recipient

How to Exchange?

Mechanism Design:  What do we want?

• Efficacy?
  • We might want to maximize the number of recipients that get a kidney.
• Fairness?
  • We don't want people to gain by being dishonest.
  • For example, if the mechanism always match the recipients with fewer available donors first, ...

Idea 1: Top Trading Cycle Algorithm

• Step 1: Every remaining recipient points to the remaining donor which provides the most compatible kidney.
• Step2: There is at least 1 cycle, and we exchange the kidneys according to the cycle(s).
• Step3: Delete the recipients and donors involved in the previous step, and go to step 1.

Idea 1: Top Trading Cycle Algorithm

Pros:

• The recipients gain nothing by misreporting.
• It provides the only allocation such that no other allocation makes every recipient gets a kidney that is "not worse".

Cons:

•  It doesn't deal with deceased donors/non-directed donations.
  • This can be solve: see Alvin E. Roth, Tayfun Sönmez, M. Utku Ünver. Kidney Exchange
• ​In kidney exchange, there is no need to find the "most compatible" kidney.
• ​It may produce long cycles.

Why are long cycles bad?

• Too many surguries that need to happen simultaneously.
  • A donor might disappear if they don't!

Idea 2: Matching

• Step 1: Every recipient reports the set of donors that can provide a compatible kidney.
• Step 2: Find a "maximum matching". 

Idea 2: Matching

Pros:

• If step 2 is implemented carefully, the recipients gain nothing by misreporting.
• The exchange is simple since we only allow cycles of length 2.
• Under the previous assumption, we still try to maximize the number of people getting a kidney.

Cons:

•  It doesn't deal with deceased donors/non-directed donations.         
  • Long chains starting from a deceased donor could be great.
• ​​​Maybe cycles of length 3 or 4 is also acceptable?

Idea 3: Just Optimize

$\max \sum_C \ell_C z_C$

s.t. $\sum_{C \in C(v)} z_C \leq 1, \forall v \in V$

$z_C \in \{0,1\}$

$\ell_C$: the length of the cycle $C$

$V$: the set of all recipient-donor pairs

$C(v)$ : the set of cycles containing $v$

Idea 3: Just Optimize

Pros:

• The number of recipients that gets a kidney is maximized.
• It can be easily modified to restrict the length of the cycles and chains.

Cons:

• There seems to be no fairness gaurantee.
• The problem is hard to solve for a computer. It might take a lot of time to compute the solution if there are too many people involved.

Enough Theory!

Kidney Exchange in the US

• Since 1988, there has been 188,677 living donor kidney transplants in the US , and 13,383 (7.1%) of them are paired donations.
• In 2024, there were 6418 living donor kidney transplants in the US, and 1443 (22.5%) of them are paired donations.

First Global Kidney Exchange in 2015

https://news.utoledo.edu/index.php/05_27_2015/ut-health-transplant-surgeon-creates-concept-to-solve-u-s-kidney-shortage

Taiwan?

• 人體器官移植條例第八條第五項(2015年新增):
  • 腎臟之待移植者未能於第一項第四款規定範圍內，覓得合適之捐贈者時，得於二組以上待移植者之配偶及該款所定血親之親等範圍內，進行組間之器官互相配對、交換及捐贈，並施行移植手術，不受該款規定之限制。
• ​衛服部2019年發布 活體腎臟交換捐贈移植手術管理辦法​

Want to know more?

• A talk by Alvin Roth: Kidney Exchange: Algorithms and Incentives
• A book by Alvin Roth about market design: Who gets what and why
• Lecture notes on algorithmic game theory by Tim Roughgarden
• Controversies in kidney exchange:
  • Winston Wing-Shing Fung, Jeremy Chapman, Masaomi Nangaku, Philip Kam-Tao Li.
    Controversies in Living Kidney Donation.​​​

References

[1] Csaba P. Kovesdy, Epidemiology of chronic kidney disease: an update 2022, Kidney International Supplements, Volume 12, Issue 1, 2022, Pages 7-11, ISSN 2157-1716, https://doi.org/10.1016/j.kisu.2021.11.003

[2] https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease

[3] Robert A Wolfe, Valarie B Ashby, Edgar L Milford, Akinlolu O Ojo, Robert E Ettenger, Lawrence YC Agodoa, Philip J Held, and Friedrich K Port. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. New England Journal of Medicine, 341(23):1725–1730, 1999.

[4] https://oncohemakey.com/how-t-cells-recognize-antigen-the-role-of-the-major-histocompatibility-complex/

[5] https://kidneydonor.org.nz/donor/guides/becoming-live-kidney-donor/kidney-exchange-programme

[6] http://kidneyregistry.com/news/60-lives-30-kidneys-all-linked/
[7] MICHAEL WALLACE. HOUSING ALLOCATION: EXISTING TENANTS AND MULTIPLE-OCCUPANCY.

[8] Danielle N. Bozek, Ty B. Dunn, Christian S. Kuhr, Christopher L. Marsh, Jeffrey Rogers, Susan E. Rees, Laura Basagoitia, Robert J. Brunner, Alvin E. Roth, Obi Ekwenna, David E. Fumo, Kimberly D. Krawiec, Jonathan E. Kopke, Puneet Sindhwani, Jorge Ortiz, Miguel Tan, Siegfredo R. Paloyo, Jeffrey D. Punch, Michael A. Rees, Complete Chain of the First Global Kidney Exchange Transplant and 3-yr Follow-up,European Urology Focus, Volume 4, Issue 2, 2018, Pages 190-197, ISSN 2405-4569, https://doi.org/10.1016/j.euf.2018.07.021.