Anatomy Lab Checklist QQ

lung adenocarcinoma

lung adenocarcinoma

colon cancer

endometrial cancer

Upper Limb

Clavicle(left)

Clavicle

spinoglenoid notch

(suprascapular notch)

(intertubercular sulcus)

obique line

Ulnar(left?)

(Palmar view of left hand)

carpal arch(tunnel)

Lower Limb

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

Skull and Facial Skeleton

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

9/19 小組討論

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

Pathology Lab 1

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)

Pathology Lab 1-2
(Infection)

可能跟ulcer一起

(可以寫多一些)

B Drug

4.0

0.01

1.01

2510

2511

breast cancer

dyslipidemia

hepatocellular carcinoma

10/3 小組討論

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

Laureates of the Nobel Prize 2024

Zi-Hong Xiao

2024/10/17

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

Pathology Micro-2

(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

11/7 小組討論

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

11/28 小組討論

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.

12/8 小組討論

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

Pathology-Micro 3

(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

Pathology-Micro 3
猜題

(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)

Pathology-Micro 4 Review

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

2. epithelial infoldings and papilla

(Nabothian cyst)

(apoptosis/prominent nucleoli)

Pathology-Micro 4

urothelium

may have squamous differentiation

loss of basal cells

or other places (skin)

1. infiltrative/non-infiltrative endometrial tumor

2. atypical columnar cells arranged in crowded and complex glands, loss of intervening stroma

3. hyperchromatic elongated pleomophic nuclei, prominent nucleoli

1. Avascular hydropic villi with central cisterns

2. Diffuse trophoblast hyperplasia with focal cytologic atypia

3. Endometrial decidual change and Arias-Stella reaction 

唯一有villi的！

1. Infiltrative tumor invading the myometrium.

2. solid sheets of atypical multinucleated syncytiotrophoblasts, mononuclear cytotrophoblasts, and intermediate trophoblasts.

3. Marked cytologic atypia: hyperchromatic enlarged pleomorphic nuclei, increased mitosis.

4. may have necrosis/hemorrhage

1. Multilocular cystic lesion lined by a single layer of tall columnar cells with abudant apical mucin

2. No definite cytologic atypia, stratification, papillary formation, or stromal invasion.

1. Infiltrative border

2. Papillary and solid growth of columnar to cuboidal tumor cells with eosinophilic cytoplasms.

3. Slit-like spaces between papillae.

4. Marked cytologic atypia: pleomorphic nuclei, prominent nucleloli, and frequent mitosis

1. Tubulocystic and papillary structures lined by cuboidal, polygonal, or round cells with clear cytoplasm.

2. Papillae have hyalinized fibrovascular core.

3. Cells with hobnail-appearance.

4. Hyperchromatic pleomorphic nuclei, prominent nucleoli

1. Well-defined tumor with mixed cystic / microcystic/ reticular pattern.

2. Cuboidal to flattened tumor cells with clear to pale eosinoplilic cytoplasm.

3. Schiller-Duval bodies and hyaline droplets.

4. Inconspicious cytologic atypia.

2. Immature neuroepithelium composed of dense small blue round cells with brisk mitosis, arranged in sheets, rosettes, pseuorosettes in a fibrillary background.

1. Well-defined tumor with mixed solid /trabecular /microfollicular patterns.

2. Call-exner bodies.

3. Uniform oval tumor cells with coffee bean-like grooved nuclei and scant eosinophilic cytoplasm.

4. Inconspicuous cytologic atypia.

感覺低機率考

1. Well-defined multi-nodular biphasic tumor and generally low cellularity.

2. Stromal spindle cells and bilayered epithelial cells without atypia.

3. Some epithelium is compressed and distorted by the collagenous to myxoid stroma.

1. Infiltrative tubules.

2. Atypical cuboidal to columnar epithelial cells with hyperchromatic enlarged pleomorphic nuclei, prominent nucleoli, and increased mitosis.

3. cribriform (or other types of) DCIS

4. stromal desmoplasia

1. Infiltrative discohesive tumor cells arranged in a single-cell or single-file pattern.

2. Uniform, small, round tumor cells with minimal cytologic atypia.

3. No stromal desmoplasia.

4. LCIS

Organ: Kidney

Diagnosis: Focal Segmental Glomerulosclerosis

Discription:

1. Interstitial fibrosis/inflammation, tubular atrophy

2. some glomeurili show segmental sclerosis and adhesion to Bowman's capsule

3. arteriosclerosis

Organ: Kidney

Diagnosis: Diabetic Nephropathy

Discription:

1. interstitial fibrosis/inflammation, tubular atrophy

2. Diffuse mesangial sclerosis

3. Nodular glomerulosclerosis

4. hyaline arteriolosclerosis

Organ: Kidney

Diagnosis: Class 4 lupus nephritis with crescents

Discription:

1. Hypercellular glomeruli with capillary wall thickening (wire loop)

2. crescent-shaped extracapillary proliferation

(3. interstitial fibrosis/inflammation, tubular atrophy)

Pathology-Micro 5

(碎塊可能是CNS)

Organ: Pituitary Gland

Diagnosis: adamantinomatous craniopharyngioma

Descriptions:

• Heterogenous tissue fragments, pale and darker regions
• Epithelial cells with peripheral palisading and central stellate reticulum
• Wet keratin with ghost cells
• Interstitial myxoid stroma

,pseudoinclusions

5. Amyloid deposition

Increased dwarf megakaryocytes

Organ: Lymph node

Diagnosis: Lymphoid hyperplasia

Descriptions:

• Increased number and size of follicles
• Follicles have distinct mantle zones and polarized germinal center
• Normal cell composition and tingible-body macrophages in the follicles

Lymph node

2/26 小組討論

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

Kidney Exchange:

Theory and Practice

https://www.kidneyfund.org/node/1437

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.

3/20 小組討論

討論問題 3：請判讀此時的抽血報告之異常。請藉由複習各種利尿劑的作用機轉，思考可能造成這種異常的藥物為何（不限定利尿劑）？依據病人此時的病況，藥物應如何調整或者加上其他藥物矯正？

Normal Ranges:

• Na: 136-145 mmol/L
• K: 3.5-5.1 mmol/L
• BUN: 7-25 mg/dL
• creatinine: 0.6-1.3 mg/dL
• pH: 7.35-7.45
• PaCO2: 35-45 mmHg
• PaO2: 80-100 mmHg
• Bicarbonate: 22-26 mmol/L

討論問題 3：請判讀此時的抽血報告之異常。請藉由複習各種利尿劑的作用機轉，思考可能造成這種異常的藥物為何（不限定利尿劑）？依據病人此時的病況，藥物應如何調整或者加上其他藥物矯正？

Diuretics: MoA

https://basicmedicalkey.com/drug-therapy-of-hypertension-edema-and-disorders-of-sodium-and-water-balance/

• Osmotic Diuretics
  • Increase tubular fluid osmolality
• ADH antagonists
  • inhibit insertion of aquaporin on collecting ducts

furosemide

spironolactone

Other Drugs

reference: micromedex

Conclusion:

Hyperkalemia: Spironolactone + Valsartan

Metabolic Alkalosis: ?? (Maybe partially by furosemide)

討論問題 3：請判讀此時的抽血報告之異常。請藉由複習各種利尿劑的作用機轉，思考可能造成這種異常的藥物為何（不限定利尿劑）？依據病人此時的病況，藥物應如何調整或者加上其他藥物矯正？

Hyperkalemia Emergency?

https://www.uptodate.com/contents/treatment-and-prevention-of-hyperkalemia-in-adults#H2

Recommendation of RAASi Use

Giuseppe M C Rosano, Juan Tamargo, Keld P Kjeldsen, Mitja Lainscak, Stefan Agewall, Stefan D Anker, Claudio Ceconi, Andrew J S Coats, Heinz Drexel, Gerasimos Filippatos, Juan Carlos Kaski, Lars Lund, Alexander Niessner, Piotr Ponikowski, Gianluigi Savarese, Thomas A Schmidt, Petar Seferovic, Sven Wassmann, Thomas Walther, Basil S Lewis, Expert consensus document on the management of hyperkalaemia in patients with cardiovascular disease treated with renin angiotensin aldosterone system inhibitors: coordinated by the Working Group on Cardiovascular Pharmacotherapy of the European Society of Cardiology, European Heart Journal - Cardiovascular Pharmacotherapy, Volume 4, Issue 3, July 2018, Pages 180–188, https://doi.org/10.1093/ehjcvp/pvy015

Patiromer

https://quizlet.com/577891973/kidney-physiology-flash-cards/

Q(A)/Discussion

討論問題 6：ACEi, ARB, DRI, MRA 這些與 RAS 相關的藥物作用機轉分別為何？哪種或哪些是被證實有腎臟保護作用的？合併使用比較好嗎？

RAAS Inhibitor

https://www.astrazeneca.com/what-science-can-do/topics/disease-understanding/unpacking-raas-pathway-role-aldosterone.html

DRI

ACEi

MRA

ARB

討論問題 6：ACEi, ARB, DRI, MRA 這些與 RAS 相關的藥物作用機轉分別為何？哪種或哪些是被證實有腎臟保護作用的？合併使用比較好嗎？

Kidney Protection

(for Non-Dialysis Chronic Kidney Disease Stages 3–5)

Zhang Y, He D, Zhang W, Xing Y, Guo Y, Wang F, Jia J, Yan T, Liu Y, Lin S. ACE Inhibitor Benefit to Kidney and Cardiovascular Outcomes for Patients with Non-Dialysis Chronic Kidney Disease Stages 3-5: A Network Meta-Analysis of Randomised Clinical Trials. Drugs. 2020 Jun;80(8):797-811. doi: 10.1007/s40265-020-01290-3. PMID: 32333236; PMCID: PMC7242277.

Direct Renin Inhibitors (DRI)?

• The AVOID Trial
  • Aliskiren may have renoprotective effects that are independent of its blood-pressure-lowering effect in patients with hypertension, type 2 diabetes, and nephropathy who are receiving the recommended renoprotective treatment.
• The ALTITUDE Trial
  • The trial was stopped prematurely after the second interim efficacy analysis
  • The addition of aliskiren to standard therapy with renin–angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful.

uptodate:Renin-angiotensin system inhibition in the treatment of hypertension

Mineralocorticoid Receptor Antagonists (MRA)?

Q(A)/Discussion

4/10 小組討論

問題一、請試圖整理這些病人的症狀，並列出您認為這位蔡小姐有什麼可能的鑑別診斷？請列出最有可能的五種，並嘗試思考應該再多詢問什麼病史、以及執行什麼理學檢查？以及她初次就診要安排什麼必要的檢查。

Symptoms

• Unintended weight loss (51kg to 47 kg in 2 months)
• Urinary frequency
• Amenorrhea for more than 6 months
• Anxiety
• Tachypnea/Exertional Dyspnea
• Insomnia
• Dry eyes
• Palpitation
• Diarrhea

Symptoms

• Unintended weight loss (51kg to 47 kg in 2 months)
• Urinary frequency
• Amenorrhea for more than 6 months
• Anxiety
• Tachypnea/Exertional Dyspnea
• Insomnia
• Dry eyes
• Palpitation
• Diarrhea

Sympathetic Overactivity?

}

Differential Diagnoses

Sympathetic Overactivity

• Diabetic autonomic neuropathy
• Anxiety disorder
• Hyperthyroidism (Thyrotoxicosis)
• Pheochromocytoma
• Drugs (adrenergic/anticholinergic)
• CNS injury

Secondary Amenorrhea

• (r/o) Pregnancy
• Intrauterine adhesions
  • ​Asherman syndrome
  • Tuberculous endometritis
• ​Disorders of the hypothalamic-pituitary-ovarian axis
  • Hyperprolactinemia
  • Thyroid disease
  • Primary ovarian insufficiency
  • hypogonadotripic hypogonadism
  • PCOS

Top 5?

References in the next page

Wakil A, Atkin S. Secondary amenorrhoea due to pheochromocytoma: a case report. Cases J. 2008 Jul 11;1(1):30. doi: 10.1186/1757-1626-1-30. PMID: 18620585; PMCID: PMC2481240.

Sackel SG, Manson JE, Harawi SJ, Burakoff R. Watery diarrhea syndrome due to an adrenal pheochromocytoma secreting vasoactive intestinal polypeptide. Dig Dis Sci. 1985 Dec;30(12):1201-7. doi: 10.1007/BF01314057. PMID: 3905308.

Kölükçü E, Gülücü S, Erdemir F. Association between lower urinary tract symptoms and polycystic ovary syndrome. Rev Assoc Med Bras (1992). 2023 May 15;69(5):e20221561. doi: 10.1590/1806-9282.20221561. PMID: 37194796; PMCID: PMC10185050.

Dybciak P, Humeniuk E, Raczkiewicz D, Krakowiak J, Wdowiak A, Bojar I. Anxiety and Depression in Women with Polycystic Ovary Syndrome. Medicina (Kaunas). 2022 Jul 16;58(7):942. doi: 10.3390/medicina58070942. PMID: 35888661; PMCID: PMC9319705.

Underdal MO, Salvesen Ø, Henriksen AH, Andersen M, Vanky E. Impaired Respiratory Function in Women With PCOS Compared With Matched Controls From a Population-Based Study. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz053. doi: 10.1210/clinem/dgz053. PMID: 31613965.

Asfuroğlu Y, Kan Ö, Asfuroğlu M, Baser E. Association Between Dry Eye and Polycystic Ovary Syndrome: Subclinical Inflammation May Be Part of the Process. Eye Contact Lens. 2021 Jan 1;47(1):27-31. doi: 10.1097/ICL.0000000000000716. PMID: 32496281.
Saei Ghare Naz M, Ghasemi V, Amirshekari S, Ramezani Tehrani F. Polycystic Ovary Syndrome and Irritable Bowel Syndrome: Is There a Common Pathway? Endocrinol Diabetes Metab. 2024 Mar;7(2):e00477. doi: 10.1002/edm2.477. PMID: 38494583; PMCID: PMC10944984.
Fava, G. A., Trombini, G., Grandi, S., Bernardi, M., Evangelisti, L. P., Santarsiero, G., & Orlandi, C. (1984). Depression and anxiety associated with secondary amenorrhea. Psychosomatics: Journal of Consultation and Liaison Psychiatry, 25(12), 905–908. https://doi.org/10.1016/S0033-3182(84)72922-7

He Q, Chen Z, Xie C, Liu L, Wei R. The Association Between Dry Eye Disease With Depression, Anxiety and Sleep Disturbance During COVID-19. Front Psychiatry. 2022 Jan 5;12:802302. doi: 10.3389/fpsyt.2021.802302. PMID: 35069294; PMCID: PMC8766963.

Uptodate: Diabetic autonomic neuropathy

Shim U, Oh JY, Lee HJ, Hong YS, Sung YA. Long menstrual cycle is associated with type 2 diabetes mellitus in korean women. Diabetes Metab J. 2011 Aug;35(4):384-9. doi: 10.4093/dmj.2011.35.4.384. Epub 2011 Aug 31. PMID: 21977458; PMCID: PMC3178699.

Tummanapalli SS, Wang LL, Dhanapalaratnam R, Poynten A, Papas EB, Krishnan AV, Markoulli M. Moderate-severe peripheral neuropathy in diabetes associated with an increased risk of dry eye disease. Optom Vis Sci. 2024 Sep 1;101(9):563-570. doi: 10.1097/OPX.0000000000002178. Epub 2024 Sep 16. PMID: 39269688.

梁怡鈴（2013）。台灣甲狀腺機能亢進症之流行病學研究。﹝碩士論文。國立成功大學﹞臺灣博碩士論文知識加值系統。 https://hdl.handle.net/11296/d86r6p。

廣泛性焦慮症-精神醫學部-三軍總醫院https://wwwv.tsgh.ndmctsgh.edu.tw/unit/10058/17028

糖尿病神經病變之診斷與治療-臺大醫院https://www.ntuh.gov.tw/neur/Fpage.action?fid=4275

問題一、請試圖整理這些病人的症狀，並列出您認為這位蔡小姐有什麼可能的鑑別診斷？請列出最有可能的五種，並嘗試思考應該再多詢問什麼病史、以及執行什麼理學檢查？以及她初次就診要安排什麼必要的檢查。

Hyperthyroidism: History/PE

Dr. 吳婉禎's 投影片

Anxiety Disorder: History/PE

For, suspected physical cause of anxiety, should do general PE and lab tests.

https://betteroutcomesnow.com/blog/gad-7-scoring/

Uptodate: Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis

PCOS: History/PE

https://www.corephilippines.com/polycystic-ovarian-syndrome-and-the-rotterdam-criteria/

Ferriman-Gallwey hirsutism scoring system

Uptodate:Diagnosis of polycystic ovary syndrome in adults

Abnormal in the US: >= 8 points

Diabetic Autonomic Neuropathy: History/PE

• Confirm DM first
• History
  • orthostatic dizziness
  • palpitation
  • bloating
  • dry skin

• PE
  • Heart rate
  • Heart rate variability
  • Orthostatic hypotension

Uptodate:Diabetic autonomic neuropathy

Pheochromocytoma: History/PE

Uptodate:Clinical presentation and diagnosis of pheochromocytoma

• History
  • Classic Triad: headache, sweating, and tachycardia​
  • young/resistant hypertension
  • familial syndrome: MEN2/NF1/VHL

• PE
  • Blood pressure​​
  • Orthostatic hypotension

Other Tests

• Hyperthyroidism: TSH, free T4, T3
• PCOS: Androgen, Transvaginal ultrasound
• Diabetic Autonomic Neuropathy: Fasting glucose, HbA1c
• Pheochromocytoma: plasma/urine fractionated metanephrines and catecholamines (CT/MRI if abnormal)

Q(A)/Discussion

問題二、基於目前的急診檢查結果，請試圖排除或納入某些診斷，您現在剩下哪一些可能的鑑別診斷？有哪些檢查您認為還需要做？病人目前在您手上，您認為他需要什麼立即的治療嗎？

Signs

• Tachypnea (respiratory rate: 30)
• Tachycardia (pulse: 125)
• Temperature : 37.3
• SpO2: 94%
• Bilateral leg pitting edema (1+)

cardiomegaly(-), lung infiltrates(-)

Lab Test Results - 1

• Polycythemia
• Microcytosis
• Thrombocytopenia
• Neutrophilic Leukocytosis
  • ​ANC: 16000 (>7700)

Lab Test Results - 2

• Elevated ALT
• Hyperglycemia?
• Elevated CRP
• Respiratory Alkalosis

Differential Diagnosis?

Covington JD, Tam CS, Pasarica M, Redman LM. Higher circulating leukocytes in women with PCOS is reversed by aerobic exercise. Biochimie. 2016 May;124:27-33. doi: 10.1016/j.biochi.2014.10.028. Epub 2014 Nov 12. PMID: 25446648; PMCID: PMC4429000.

Michael, Sarah E. MD1; Darbinian, Jeanne A. MPH2; Ramalingam, Nirmala D. MPP1; Wu, Stephanie J. MD1; Khil, Jaclyn MD1; Lo, Joan C. MD2; Greenspan, Louise C. MD3. S1156 PCOS Is an Independent Predictor of Elevated ALT in Adolescent Girls With Obesity. The American Journal of Gastroenterology 115():p S578-S579, October 2020. | DOI: 10.14309/01.ajg.0000706672.34009.10

Uptodate: Approach to the patient with neutrophilia

Baruah MP, Bhattacharya B. Significant role of serum CRP in differentiating inflammatory from non-inflammatory causes of thyrotoxicosis. Indian J Endocrinol Metab. 2012 Nov;16(6):976-81. doi: 10.4103/2230-8210.103002. PMID: 23226645; PMCID: PMC3510970.

N. Boulman, Y. Levy, R. Leiba, S. Shachar, R. Linn, O. Zinder, Z. Blumenfeld, Increased C-Reactive Protein Levels in the Polycystic Ovary Syndrome: A Marker of Cardiovascular Disease, The Journal of Clinical Endocrinology & Metabolism, Volume 89, Issue 5, 1 May 2004, Pages 2160–2165, https://doi.org/10.1210/jc.2003-031096

問題二、基於目前的急診檢查結果，請試圖排除或納入某些診斷，您現在剩下哪一些可能的鑑別診斷？有哪些檢查您認為還需要做？病人目前在您手上，您認為他需要什麼立即的治療嗎？

Other Tests?

• Blood Pressure
• Hyperthyroidism: TSH, free T4, T3
• Diabetic Autonomic Neuropathy: HbA1c
• Pheochromocytoma: plasma/urine fractionated metanephrines and catecholamines (CT/MRI if abnormal)

問題二、基於目前的急診檢查結果，請試圖排除或納入某些診斷，您現在剩下哪一些可能的鑑別診斷？有哪些檢查您認為還需要做？病人目前在您手上，您認為他需要什麼立即的治療嗎？

Immediate Intervention?

• Neutrophilic leukocytosis?
  • no hypotension, high fever, hypothermia, abdominal rebound tenderness
• ​Tachycardia
  • ​Should treat underlying cause.
• ​Respiratory Alkalosis
  • ​Rarely life-threatening, should correct underlying disorder.
• ​Tachypnea
  • ​Should treat
  • 給氧氣？

Uptodate:Approach to the patient with neutrophilia, Sinus tachycardia: Evaluation and management, 

Q(A)/Discussion

5/1 小組討論

問題一：食道癌常見的組織學型態與對應的危險因子有哪些？

民國111年癌症登記報告

Squamous Cell Caricinoma

Adenocarcinoma

Carcinoma, NOS

Adenosquamous Carcinoma

NET/NEC

1

2

3

鱗狀上皮癌(Squamous Cell Carcinoma, SCC)

pictures from ExpertPath

Well-differentiated SCC

basaloid SCC

sarcomatoid SCC

Risk Factors for Esophageal SCC

• Smoking, Alcohol, Hot tea
• Demographic factors
  • Incidence higher in East Asia, East Africa, Southern Africa
• Age
  • Rare before 30, median: 65
• HPV
• Sex?

  • In high-incidence regions, the disease has no sex specificity. By contrast, SCC is more common in males in low-incidence regions.

腺癌(Adenocarcinoma)

pictures from Pathology Outlines

Tubular Pattern

Signet Ring Cell Pattern

Risk Factors for Esophageal Adenocarcinoma

• 胃食道逆流(GERD)/Barrett's Esophagus

https://castlebiosciences.com/patient-information/gastroenterology/barretts-esophagus/overview

Risk Factors for Esophageal Adenocarcinoma

• Obesity/Metabolic Syndrome
  • May be independent of GERD
• Smoking
  • Not as strong as SCC
• Diet low in fruits and vegetables
• Male

神經內分泌腫瘤/癌 (NET/NEC)

https://ar.iiarjournals.org/content/33/2/595

Small Cell Carcinoma

Q(A)/Discussion

問題三：概述免疫檢查點抑制劑（immune checkpoint inhibitor，programmed cell death-1 [PD1]及 programmed death-ligand-1 [PD-L1]）在癌症的發展？

免疫檢查點 (Immune Checkpoints)

2018 諾貝爾生醫獎

The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252- 264.

 ipilimumab: Approved in 2010 for melanoma

Hodi FS, O'day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC et al: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010, 363(8): 711-723.

anti-CTLA4 antibody

https://www.kcuk.org.uk/ipilimumab-yervoy/

PD-L1 on Tumor Cells?

The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252- 264.

Makuku, Rangarirai, Khalili, Neda, Razi, Sepideh, Keshavarz-Fathi, Mahsa, Rezaei, Nima, Current and Future Perspectives of PD-1/PDL-1 Blockade in Cancer Immunotherapy, Journal of Immunology Research, 2021, 6661406, 15 pages, 2021. https://doi.org/10.1155/2021/6661406

FDA-approved indications for PD-1 Inhibitors

• Pembrolizumab

  Melanoma

  Breast cancer

  Non-small-cell lung cancer

  Small-cell lung cancer

  Head and neck squamous cell cancer

  Hodgkin lymphoma

  Gastric/gastroesophageal junction (GEJ) adenocarcinoma

  Cervical cancer

  Endometrial carcinoma

  Primary mediastinal large B cell lymphoma

  Hepatocellular carcinoma

  Merkel cell carcinoma

  Renal cell cancer

  Urothelial cancer

• Nivolumab

  Melanoma

  Non-small-cell lung cancer

  Small-cell lung cancer

  Renal cell cancer

  Hodgkin lymphoma

  Head and neck squamous cell cancer

  Urothelial cancer

  Colorectal cancer

  Hepatocellular carcinoma

  Metastatic esophageal squamous cell carcinoma (ESCC)

• Cemiplimab
  Cutaneous squamous cell carcinoma

Makuku, Rangarirai, Khalili, Neda, Razi, Sepideh, Keshavarz-Fathi, Mahsa, Rezaei, Nima, Current and Future Perspectives of PD-1/PDL-1 Blockade in Cancer Immunotherapy, Journal of Immunology Research, 2021, 6661406, 15 pages, 2021. https://doi.org/10.1155/2021/6661406

FDA-approved indications for PD-L1 Inhibitors

• Atezolizumab

  Urothelial carcinoma

  Non-small-cell lung cancer

  Small-cell lung cancer

  Hepatocellular carcinoma

  Breast cancer

• Durvalumab

  Urothelial carcinoma

  Non-small-cell lung cancer

  Small-cell lung cancer

• Avelumab

  Merkel cell carcinoma

  Urothelial carcinoma

  Renal cell cancer

Makuku, Rangarirai, Khalili, Neda, Razi, Sepideh, Keshavarz-Fathi, Mahsa, Rezaei, Nima, Current and Future Perspectives of PD-1/PDL-1 Blockade in Cancer Immunotherapy, Journal of Immunology Research, 2021, 6661406, 15 pages, 2021. https://doi.org/10.1155/2021/6661406

Biomarkers for Immune Checkpoint Inhibitors

• PD-L1 expression
• Tumor mutational burden
• Microsatellite instability-high

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

The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252- 264.

Future Prospects: Combinations?

• vaccines
• target therapy
• chemotherapy
• ...

Q(A)/Discussion

Last Micro

organ CNS寫brain, soft tissue寫soft tissue

(circumscribed)

(well-defined)

• A complex branching papillary structure covered by a single layer of uniform cuboid to columnar epithelial cells
• psammomatous calcification

(well-defined)

• Organ: Bone (joint)
• Diagnosis: Osteoarthritis
• Description
  • Cartilage degeneration:
    • chondrocyte clustering
    • surface fibrillation, fissures, cartilage thinning
    • Tidemark duplication
  • Subchondral bone change: sclerosis, subchondral cyst
  • synovial hyperplasia, inflammatory cell infiltrate, fibrosis

(chondrocytes arranged in columns at base)

• Organ: Skin
• Diagnosis: Dermatofibroma
• Description
  • A poorly circumscribed dermal tumor with peripheral collagen trapping
  • Areas of hypercellularity or hypocellularity
  • Fascicles or whorls of spincle cells or histiocytic cells
  • May have epidermal hyperplasia or basal  hyperpigmentation