26. Sedatives, as premedication, must be avoided in which of the following patients?

A. Uncontrolled hypertensive

B. Toddler for tonsillectomy

C. Brain tumor patients

D. Patients with alcohol abuse

27. As per the American Society of Regional Anesthesia (ASRA) guidelines, which of

the following drugs can be continued preoperatively in patients planned for neuraxial

blockade for an elective procedure?

A. Aspirin

B. Clopidogrel

C. Warfarin

D. Low-molecular-weight heparin

28. As per ASA classification, a controlled hypertensive patient with no target end-organ

damage scheduled for elective surgery will be classified as

A. ASA I

B. ASA II

C. ASA III

D. ASA VI

29. A brain-dead organ donor undergoing laparotomy for “kidney harvesting” will be

classified as an

A. ASA III

B. ASA IV

C. ASA V

D. ASA VI

30. A moribund patient who is not expected to survive without the operation is

categorized as an

A. ASA III

B. ASA IV

C. ASA V

D. ASA VI

31. A patient with a history of uncontrolled hypertension, diabetes, and angina, who is to

undergo a laparoscopic cholecystectomy, will be classified as an

A. ASA II

B. ASA III

C. ASA IV

D. ASA V

32. A 65-year-old male with a history of mitral valve replacement 2 years back presents

for a knee replacement. He is on warfarin since the time of valve replacement. As

per ASRA guidelines, the ideal time to stop his warfarin prior to surgery would be

A. 12 hours

B. 3 days

C. 5 days

D. 10 days

33. A 26-year-old female, with a history of rheumatic mitral stenosis, is scheduled for an

elective cesarean section at 38 weeks of gestation. Just prior to surgery, she is

diagnosed to have atrial fibrillation (AF) with no hemodynamic instability. The first

step in preparation for surgery is

A. Perform an echocardiogram to rule out left-atrial clot

B. Synchronized DC cardioversion under sedation

C. Antiarrhythmic medication

D. Plan for therapy postdelivery

34. A 72-year-old patient with a history of hypertension and angina at moderate activity

is to undergo a laparoscopic cholecystectomy. Due to decreased effort tolerance and

a significant blockade of left anterior descending coronary artery onstress thallium, a

preprocedure coronary intervention is planned. Which of the following procedures

performed prior to the elective surgery is least likely to delay the laparoscopic

surgery?

A. Coronary artery bypass graft (CABG)

B. Percutaneous coronary stenting—bare-metallic stent

C. Percutaneous coronary stenting—drug-eluting stent

D. Percutaneous balloon dilatation

35. Which of the following is not seen as a result of primary renal disease in patients

with chronic renal failure?

A. Hypocoagulable state

B. Hypercoagulable state

C. Hyperproteinemia

D. Anemia

36. A 2-year-old child is to undergo a tonsillectomy. The child had formula milk 2 hours

ago. As per ASA guidelines, optimal NPO status would be to wait another _____

before proceeding to surgery:

A. No waiting, since it is a child

B. 2 hours

C. 4 hours

D. 6 hours

37. A 45-year-old patient is scheduled for an abdominal hysterectomy. She states that

her aunt had a severe reaction to anesthesia and was in the ICU for 1 week. You

would avoid which of the following drugs for her general anesthesia?

A. Droperidol

B. Ketamine

C. Sevoflurane

D. Etomidate

38. Elective surgery should be postponed after a myocardial infarction for at least

A. 30 days

B. 6 weeks

C. 3 months

D. 6 months

39. The most significant risk factor for developing pulmonary complications is

A. Site of surgery (abdominal/thoracic)

B. Presence of respiratory infection

C. Presence of obstructive sleep apnea

D. Smoking

40. Maximum international normalized ratio (INR) before proceeding for elective

surgery should be

A. 1.0

B. 1.2

C. 1.4

D. 1.6

41. A 73-year-old patient has residual weakness on the right arm and leg following a

stroke 5 years ago. He is now scheduled for laparoscopic cholecystectomy under

general anesthesia. Which of the following sites should be preferably used to monitor

the train of four muscle twitches for estimating neuromuscular blockade?

A. Right ulnar nerve–innervated muscles

B. Right posterior tibial nerve–innervated muscles

C. Left ulnar nerve–innervated muscles

D. Left facial nerve

42. A 32-year-old patient after being involved in a road traffic accident due to alcohol

intoxication is taken to the operating room for open fracture reduction of an ankle

fracture. His blood alcohol level is above the legal limit. Compared to a patient who

is not intoxicated with alcohol, you would expect the minimum alveolar

concentration (MAC) of sevoflurane to be

A. Higher

B. Lower

C. Equal

D. Unpredictable due to pharmacodynamic variations

43. A 55-year-old patient with a history of asthma and heart failure is to undergo a

hernia repair. On physical examination, you notice that the patient is wheezing.

Following treatment with albuterol, the patient should be monitored for which

electrolyte?

A. Potassium

B. Calcium

C. Sodium

D. Chloride

44. Smoking cessation for 24 hours before a scheduled surgery will lead to

A. Improvement of ciliary function

B. Decrease in mucous production

C. Decrease in airway irritability

D. Decrease in level of carboxyhemoglobin

45. Which of the following tests is likely to detect clinically relevant bleeding tendency

most efficiently?

A. Activated partial thromboplastin time

B. Prothrombin time

C. Activated clotting time

D. Thromboelastogram (TEG)

46. As per AHA guidelines, which of the following is not a major clinical risk predictor

in a patient with cardiac disease scheduled for noncardiac surgery?

A. Recent myocardial infarction

B. Symptomatic mitral stenosis

C. Presence of congestive cardiac failure

D. Uncontrolled systolic hypertension

47. Glycopyrrolate, when given preoperatively, can cause all of the following, except

A. Skin flushing

B. Dry mouth

C. Bronchoconstriction

D. Tachycardia

48. Which of the following is true about metoclopramide?

A. Decreases lower esophageal sphincter tone

B. Delays gastric emptying

C. Can cause extrapyramidal side effects

D. Useful in preventing postoperative nausea

49. Which of the following occurs during the preoxygenation of a patient?

A. Increase in functional residual capacity

B. Denitrogenation

C. Increase in CO2 clearance from lungs

D. Increase in closing capacity of lungs

50. Which of the following agents is associated with the highest incidence of hepatitis

postoperatively?

A. Halothane

B. Isoflurane

C. Desflurane

D. Sevoflurane

51. The inhalation agent of choice in a 2-year-old child for ophthalmologic surgery is

A. Halothane

B. Desflurane

C. Sevoflurane

D. Nitrous oxide

52. Which of the following is true of nitrous oxide?

A. Acts on central nervous system GABA receptors

B. Lowers pulmonary vascular resistance

C. Suppresses EEG pattern in the cerebral cortex

D. Precipitates vitamin B12 deficiency anemia

53. The antiemetic effect of propofol is thought to occur due to

A. Depressant effect on the chemoreceptor trigger zone

B. Inhibition of dopamine activity

C. Inhibition of glutamate release

D. All of the above

54. Which of the following is the preferred intravenous agent of induction of anesthesia

for maintaining spontaneous breathing and airway tone?

A. Midazolam

B. Propofol

C. Ketamine

D. Diazepam

55. Succinylcholine is contraindicated in a patient with

A. Chronic renal failure

B. Duchene muscular dystrophy

C. Myasthenia gravis

D. Patient with full stomach

56. A 75-year-old patient with a history of hypertension is to undergo laparoscopic

colectomy for carcinoma colon. Continuing of which of the following

antihypertensive drugs, preoperatively, in the geriatric age group, can be associated

with profound hypotension on induction of general anesthesia?

A. Metoprolol

B. Angiotensin-converting-enzyme (ACE) inhibitors

C. Hydrochlorothiazide

D. Furosemide

57. Which of the following findings in the preoperative evaluation cannot be attributed to

obesity with obstructive sleep apnea (OSA) in a patient planned for bariatric

surgery?

A. Pulmonary artery hypertension

B. Congestive heart failure

C. Peripheral neuropathy

D. Dementia

58. All of the following medications can be administered via an epidural anesthesia,

except

A. Fentanyl

B. Sufentanil

C. Alfentanil

D. Remifentanil

59. Ondansetron causes its antiemetic effect by acting as an

A. Agonist at 5-HT2

receptors

B. Antagonist at 5-HT2

receptors

C. Agonist at 5-HT3

receptors

D. Antagonist at 5-HT3

receptors

60. Which of the following statements is false regarding scopolamine patch applied

preoperatively?

A. May produce sedation

B. Decreases the risk of nausea

C. Adds to the analgesia

D. Inhibits muscarinic receptors

61. Overdose with dexmedetomidine results 

Overdose with dexmedetomidine results in

A. Hypertension

B. Bradycardia

C. Hypertension and bradycardia

D. Hypotension and bradycardia

62. Abrupt withdrawal of steroids can lead to

A. Malignant hypertension

B. Sickle cell crisis

C. Addisonian crisis

D. Psychosis

63. Promethazine primarily inhibits which of the following receptors?

A. Serotonin

B. Dopamine

C. Muscarinic

D. Acetylcholine

64. All of the following surgeries are associated with an increased risk of postoperative

nausea and vomiting, except

A. Shoulder arthroscopy

B. Laparoscopic surgery

C. Strabismus repair

D. Tympanoplasty

65. Abrupt stoppage of total parenteral nutrition (TPN) would most likely cause

A. Hypoglycemia

B. Hyperglycemia

C. Hyperphosphatemia

D. Hypophosphatemia

66. Glycopyrrolate causes all of the following, except

A. Sedation

B. Tachycardia

C. Antisialagogue effect

D. Lowers lower esophageal sphincter tone

67. In general, herbal medications should be stopped before surgery for at least _____

days:

A. 3

B. 7

C. 10

D. 14

68. Which of the following antibiotics can prolong the action of neuromuscular-blocking

drugs?

A. Gentamicin

B. Penicillin

C. Levofloxacin

D. Cephalexin

69. Estrogen in birth control pills increases the perioperative risk of

A. Diarrhea

B. Thromboembolism

C. Stroke

D. Myocardial infarction

 

who selflessly pass on their values and knowledge to us

Mian Ahmad, MD

Department of Anesthesiology and Perioperative Medicine, Drexel University College of

Medicine, Philadelphia, Pennsylvania

Sheri M. Berg, MD

Instructor, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts

General Hospital, Boston, Massachusetts

Edward A. Bittner, MD, PhD, FCCP, FCCM

Program Director, Critical Care Medicine-Anesthesiology Fellowship, Associate Director,

Surgical Intensive Care Unit, Assistant Professor of Anaesthesia, Harvard Medical

School, Massachusetts General Hospital, Department of Anesthesia, Critical Care, and

Pain Medicine, Boston, Massachusetts

Yuriy S. Bronshteyn, MD

Surgical Critical Care Fellow, Massachusetts General Hospital, Department of Anesthesia,

Critical Care, and Pain Medicine, Boston, Massachusetts

Thomas M. Halaszynski, DMD, MD, MBA

Associate Professor of Anesthesiology, Director of Regional Anesthesia/Acute Pain

Medicine, Department of Anesthesiology, Yale University School of Medicine, Yale

New Haven Hospital, New Haven, Connecticut

Darrin J. Hyatt, MD

Anesthesia Chief Resident, Department of Anesthesia, Critical Care, and Pain Medicine,

Massachusetts General Hospital, Boston, Massachusetts

Daniel W. Johnson, MD

Assistant Professor, Fellowship Director, Critical Care Anesthesiology, Department of

Anesthesiology, University of Nebraska Medical Center, Omaha, Nebraska

Rebecca Kalman, MD

Clinical Instructor in Anesthesia, Massachusetts General Hospital, Boston, Massachusetts

Jean Kwo, MD

Anesthesiologist, Department of Anesthesia, Critical Care, and Pain Medicine,

Massachusetts General Hospital, Assistant Professor of Anaesthesia, Harvard Medical

School, Boston, Massachusetts

Jinlei Li, MD

Assistant Professor of Anesthesiology, Yale University School of Medicine, Yale New

Haven Hospital, New Haven, Connecticut

Dipty Mangla, MD

Staff Anesthesiologist, Cumberland Pain Management, Cumberland, Maryland

Ala Nozari, MD

Assistant Professor, Department of Anesthesia, Critical Care, and Pain Medicine,

Massachusetts General Hospital, Boston, Massachusetts

Thoha M. Pham, MD

Associate Clinical Professor, University of California, San Francisco (UCSF), Department

of Anesthesia and Perioperative Care, San Francisco, California

Manish Purohit, MD

Department of Anesthesiology and Perioperative Medicine, Drexel University College of

Medicine, Philadelphia, Pennsylvania

Paul Sikka, MD, PhD

Department of Anesthesia and Perioperative Medicine, Signature Healthcare Brockton

Hospital, Brockton, Massachusetts, Affiliate of Beth Israel Deaconess Medical Center,

Boston, Massachusetts (Former Faculty—Brigham and Women’s Hospital, Harvard

Medical School)

Ashish C. Sinha, MD, PhD, DABA

Vice Chairman, Anesthesiology & Critical Care, Drexel University College of Medicine,

Hahnemann University Hospital, Philadelphia, Pennsylvania

Preet Mohinder Singh, MD

Department of Anesthesia, All India Institute of Medical Sciences, New Delhi, India

David L. Stahl, MD

Clinical Fellow, Department of Anesthesia, Critical Care and Pain Medicine,

Massachusetts General Hospital, Boston, Massachusetts

Deppu Ushakumari, MD

Department of Anesthesiology and Perioperative Medicine, Drexel University College of

Medicine, Philadelphia, Pennsylvania

The practice of anesthesiology requires a solid foundation of knowledge. It is with extreme

pleasure that we introduce Lippincott’s Anesthesia Review: 1,001 Questions and Answers.

The book is designed to rapidly review anesthesiology to help residents pass the written

examinations taken during and after residency. The book is broadly divided into 21

chapters to cover almost all relevant topics tested. Each question is followed by four

possible answers, among which one is the best or most likely answer.

The editors acknowledge the work of all who have given their valuable time and effort

to complete this book. These include all authors, proofreaders (including Shilpa Shah,

MD), and the team at Lippincott Williams & Wilkins. We would also like to thank our

families for their support while we prepared this manuscript.

We hope that this review book proves to be a valuable educational resource for

anesthesia residents and young practitioners to help them pass the boards. For any

constructive suggestions, please contact us by email: Anes1001@outlook.com.

The Editors

Contributors

Preface

1. Perioperative Evaluation and Management

PREET SINGH, MANISH PUROHIT, ASHISH SINHA, AND PAUL SIKKA

2. Airway Management

YURIY BRONSHTEYN AND EDWARD BITTNER

3. Anesthesia Machine

PAUL SIKKA

4. Patient Monitoring

DARREN HYATT, ALA NOZARI, AND EDWARD BITTNER

5. Fluid Management and Blood Transfusion

REBECCA KALMAN AND EDWARD BITTNER

6. Anesthetic Pharmacology

MIAN AHMAD AND ASHISH SINHA

7. Spinal and Epidural Anesthesia

THOMAS HALASZYNSKI

8. Peripheral Nerve Blocks

THOMAS HALASZYNSKI

9. Pain Management

THOMAS HALASZYNSKI

10. Orthopedic Anesthesia

THOMAS HALASZYNSKI

11. Cardiovascular Anesthesia

DEPPU USHAKUMARI AND ASHISH SINHA

12. Thoracic Anesthesia

DEPPU USHAKUMARI AND ASHISH SINHA

13. Neuroanesthesia

DIPTY MANGLA AND ASHISH SINHA

14. Gastrointestinal, Liver, and Renal Diseases

THOHA PHAM

15. Endocrine Diseases

JEAN KWO AND EDWARD BITTNER

16. Ophthalmic, Ear, Nose, and Throat Surgery

THOHA PHAM

17. Obstetric Anesthesia

THOHA PHAM

18. Pediatric Anesthesia

DIPTY MANGLA AND ASHISH SINHA

19. Critical Care

DAVID STAHL, DANIEL JOHNSON, AND EDWARD BITTNER

20. Postoperative Anesthesia Care

SHERI BERG AND EDWARD BITTNER

21. Miscellaneous Topics

PAUL SIKKA AND THOMAS HALASZYNSKI

Perioperative Evaluation and Management

Preet Singh, Manish Purohit, Ashish Sinha, and Paul Sikka

1. Preoperative application of scopolamine patch to prevent postoperative nausea and

vomiting should be avoided in

A. Female, 35 years old

B. Smoker, 20 years old

C. Patient with a blood pressure of 160/96 mm Hg

D. Male, 70 years old

2. Which of the following drugs is least likely to be effective for prophylaxis for

postoperative nausea and vomiting?

A. Ondansetron

B. Scopolamine patch

C. Aprepitant

D. Metoclopramide

3. Famotidine, when used for stress ulcer prophylaxis, must be avoided preoperatively

in which of the following patients?

A. Patients with replaced mitral valve on warfarin

B. Patients with idiopathic thrombocytopenic purpura (ITP) for splenectomy

C. Patients with achalasia cardia for esophageal myotomy

D. Patients with a history of coronary stenting on aspirin

4. Which of the following drugs antagonizes substance P in the central nervous system

and is used as premedication to prevent postoperative nausea and vomiting?

A. Palonosetron

B. Aprepitant

C. Metoclopramide

D. Prochlorperazine

5. Which of the following predictors is likely to be associated with lower incidence of

perioperative nausea and vomiting?

A. Female gender

B. Use of fentanyl for pain relief

C. Patients with a history of smoking

D. Patients undergoing laparoscopic surgery

6. All of the following have an antiemetic action, except

A. Promethazine

B. Propofol

C. Etomidate

D. Haloperidol

7. Cefazolin, as a component of perioperative antimicrobial prophylaxis for surgery,

must begin within what time before incision?

A. Simultaneously with incision

B. Within 30 minutes prior to incision

C. Within 60 minutes prior to incision

D. Within 120 minutes prior to incision

8. Vancomycin, as a component of perioperative antimicrobial prophylaxis for surgery,

must begin within what time before incision?

A. Simultaneously with incision

B. Within 30 minutes prior to incision

C. Within 60 minutes prior to incision

D. Within 120 minutes prior to incision

9. A 65-year-old male with a history of hypertension and diabetes presents to

emergency department with altered sensation with a likely subdural hematoma. To

assess his cardiorespiratory status, he is asked about his level of physical activity. If

he is capable of performing at least which of the following activities independently,

he is less likely to have significant cardiopulmonary ailment during surgery?

A. Walk to washroom on level floor

B. Play the accordion

C. Walk one block

D. Climb a flight of stairs

10. In preoperative assessment of patients, physical activity is graded in terms of

metabolic equivalents (METs). The value that corresponds to oxygen consumption

of 1 MET in an adult is

A. 2 mL/kg/min

B. 7 mL/kg/min

C. 3.5 mL/kg/min

D. 5.5 mL/kg/min

11. As per American Society of Regional Anesthesia (ASRA) guidelines, intravenous

infusion of unfractionated heparin should be stopped how long prior to a planned

epidural?

A. 1 to 1.5 hours

B. 2 to 4 hours

C. at least 12 hours

D. at least 24 hours

12. For emergent surgery, anticoagulation produced by warfarin can be reversed by

using

A. Fresh-frozen plasma (FFP)

B. Injectable vitamin K

C. Prothrombin complex concentrate

D. Factor VIII concentrate

13. Neuraxial block is not contraindicated for patients on which of the following drugs?

A. Warfarin

B. Low-molecular-weight heparin

C. Aspirin

D. Clopidogrel

14. All of the following are risk factors for obstructive sleep apnea, except

A. Obesity

B. Short neck

C. Enlarged tonsils

D. Female gender

15. A 70-year-old male, who is diabetic for the last 20 years, is scheduled for an

elective surgery. Which of the following is not a sign of autonomic diabetic

neuropathy?

A. History of recurrent diarrhea

B. History of postural hypotension

C. History of recurrent constipation

D. History of urinary retention

16. Which of the following perioperative factors in patients undergoing dialysis prior to

surgery predicts the possibility of hypotension (due to increased volume removed)?

A. Change in serum sodium

B. Change in body weight

C. Change in serum potassium

D. Change in pH after dialysis

17. A patient with a history of severe asthma is scheduled for an appendectomy. Which

of the following induction agents will cause the least respiratory depression?

A. Ketamine

B. Propofol

C. Etomidate

D. Thiopental

18. Which of the following drugs can significantly prolong the QT interval on the ECG?

A. Dexamethasone

B. Droperidol

C. Aprepitant

D. Glycopyrrolate

19. Which of the following tests is used to confirm coagulation after stopping lowmolecular-weight heparin (LMWH)?

A. PT

B. aPTT

C. ACT

D. None of the above

20. Effect of combined administration of midazolam and fentanyl is

A. Additive

B. Synergistic

C. Competitively antagonistic

D. Noncompetitively antagonistic

21. Preoperative anesthetic evaluation is likely to bring down the incidence of all the

following, except

A. Case cancellations

B. Patient morbidity

C. Preoperative anxiety

D. Direct procedural costs

22. For elective procedures, an anesthesia provider must obtain informed and preferably

written consent

A. Just prior to transferring the patient to the operating room for surgery

B. During preoperative anesthetic evaluation

C. At the same time that a surgeon obtains consent for the surgical procedure

D. Just prior to induction of anesthesia in the operating room

23. An optimal preoperative evaluation is designed

A. To screen for and properly manage comorbid conditions

B. To assess the risk of anesthesia and surgery and lower it

C. To identify patients who may require special anesthetic techniques or

postoperative care

D. All the above

24. ASA classification for risk stratification is validated for predicting preoperative

morbidity associated with the following, except

A. General or regional anesthesia

B. Conscious sedation

C. Monitored anesthesia care

D. Surgical procedure

25. A healthy pregnant patient in labor has which of the following ASA classifications?

A. I

B. II

C. III

D. IV

 1,001

QUESTIONS AND ANSWERS

Paul Sikka, MD, PhD

Department of Anesthesia and

Perioperative Medicine

Signature Healthcare Brockton Hospital,

Brockton, Massachusetts

Af iliate of Beth Israel Deaconess Medical

Center, Boston, Massachusetts (Former

Faculty—Brigham and Women’s Hospital,

Harvard Medical School)

Edward A. Bittner, MD, PhD, FCCP, FCCM

Program Director, Critical Care Medicine-Anesthesiology

Fellowship, Associate

Director, Surgical Intensive Care Unit,

Assistant Professor of Anaesthesia,

Harvard Medical School, Massachusetts

General Hospital, Department of

Anesthesia, Critical Care, and Pain

Medicine, Boston, Massachusetts

Thomas M. Halaszynski, DMD, MD, MBA

Associate Professor of Anesthesiology,

Director of Regional Anesthesia/

Acute Pain Medicine, Department of

Anesthesiology, Yale University School of

Medicine, Yale New Haven Hospital, New

Haven, Connecticut

Thoha M. Pham, MD

Associate Clinical Professor, University

of California, San Francisco (UCSF),

Department of Anesthesia and

Perioperative Care, San Francisco, California

Ashish C. Sinha, MD, PhD, DABA

Vice Chairman, Anesthesiology &

Critical Care, Drexel University College

of Medicine, Hahnemann University

Hospital, Philadelphia, Pennsylvania

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Product Development Editor: Nicole Dernoski

Editorial Assistant: Lindsay Burgess

Production Project Manager: Bridgett Dougherty

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Marketing Manager: Dan Dressler

Prepress Vendor: S4C Publishing Services

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Lippincott’s anesthesia review : 1001 questions and answers / Paul Sikka, Edward Bittner, Thomas Halaszynski, Thoha

Pham, Ashish Sinha.

p. ; cm.

Anesthesia review

E-ISBN: 978-1-4698-3101-5

I. Bittner, Edward A., 1967- author. II. Halaszynski, Thomas, author. III. Pham, Thoha, author. IV. Sinha, Ashish, author.

V. Title. VI. Title: Anesthesia review.

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ABSTRACT

The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility. It is unclear whether these side effects are coupled to the chemotherapeutic efficacy. Doxo, Daun, Epi, and Ida execute two cellular activities: DNA damage, causing double-strand breaks (DSBs) following poisoning of topoisomerase II (Topo II), and chromatin damage, mediated through histone eviction at selected sites in the genome. Here we report that anthracycline-induced cardiotoxicity requires the combination of both cellular activities. Topo II poisons with either one of the activities fail to induce cardiotoxicity in mice and human cardiac microtissues, as observed for aclarubicin (Acla) and etoposide (Etop). Further, we show that Doxo can be detoxified by chemically separating these two activities. Anthracycline variants that induce chromatin damage without causing DSBs maintain similar anticancer potency in cell lines, mice, and human acute myeloid leukemia patients, implying that chromatin damage constitutes a major cytotoxic mechanism of anthracyclines. With these anthracyclines abstained from cardiotoxicity and therapy-related tumors, we thus uncoupled the side effects from anticancer efficacy. These results suggest that anthracycline variants acting primarily via chromatin damage may allow prolonged treatment of cancer patients and will improve the quality of life of cancer survivors.

PMID:32554494 | DOI:10.1073/pnas.1922072117

05:03

PubMed articles on: Cancer & VTE/PE

Cancer-associated venous thromboembolism: Treatment and prevention with rivaroxaban

Bauersachs R, et al. Res Pract Thromb Haemost 2020 - Review.

ABSTRACT

Cancer-associated venous thromboembolism (VTE) is a frequent, potentially life-threatening event that complicates cancer management. Anticoagulants are the cornerstone of therapy for the treatment and prevention of cancer-associated thrombosis (CAT); factor Xa-inhibiting direct oral anticoagulants (DOACs; apixaban, edoxaban, and rivaroxaban), which have long been recommended for the treatment of VTE in patients without cancer, have been investigated in this setting. The first randomized comparisons of DOACs against low-molecular-weight heparin for the treatment of CAT indicated that DOACs are efficacious in this setting, with findings reflected in recent updates to published guidance on CAT treatment. However, the higher risk of bleeding events (particularly in the gastrointestinal tract) with DOACs highlights the need for appropriate patient selection. Further insights will be gained from additional studies that are ongoing or awaiting publication. The efficacy and safety of DOAC thromboprophylaxis in ambulatory patients with cancer at a high risk of VTE have also been assessed in placebo-controlled randomized controlled trials of apixaban and rivaroxaban. Both studies showed efficacy benefits with DOACs, but both studies also showed a nonsignificant increase in major bleeding events while on treatment. This review summarizes the evidence base for rivaroxaban use in CAT, the patient profile potentially most suited to DOAC use, and ongoing controversies under investigation. We also describe ongoing studies from the CALLISTO (Cancer Associated thrombosis-expLoring soLutions for patients through Treatment and Prevention with RivarOxaban) program, which comprises several randomized clinical trials and real-world evidence studies, including investigator-initiated research.

PMID:32548552 | PMC:PMC7292665 | DOI:10.1002/rth2.12327

05:03

PubMed articles on: Cardio-Oncology

Successful Heart Transplant in a Childhood Cancer Survivor With Chemoradiotherapy-Induced Cardiomyopathy

Sipahi NF, et al. Exp Clin Transplant 2020.

ABSTRACT

Cancer therapy-related cardiotoxicity has been presenting a major problem in cancer survivors, who constitute a growing population caused by a significant improvement in cancer therapy during the past decades. Although some listing criteria have been defined for these patients, it is still a compelling decision to list patients with a complex cancer anamnesis. We describe herein a childhood cancer survivor after a cancer anamnesis with 2 different malignancies and an end-stage heart failure following chemoradiotherapy who was successfully treated with orthotopic heart transplant.

PMID:32552629 | DOI:10.6002/ect.2020.0062

05:03

PubMed articles on: Cancer & VTE/PE

microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors

Oto J, et al. Cancers (Basel) 2020.

ABSTRACT

Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with intracranial tumors are more likely to develop VTE than patients with cancers at other sites. Conversely, limited tools exist to identify patients with high thrombotic risk. Upon activation, neutrophils release their content through different mechanisms triggering thrombosis. We explored the ability of microRNAs (miRNAs) and plasma markers of neutrophil activation measured before surgery to predict the risk of early post-surgical pulmonary embolism (PE) in glioma and meningioma patients. We recruited and prospectively followed 50 patients with glioma and 50 with meningioma, 34% of whom in each group developed an early objectively-diagnosed post-surgical PE. We measured miRNA expression and neutrophil markers (cell-free DNA, nucleosomes, calprotectin and myeloperoxidase) before surgery. In glioma patients, we adjusted and validated a predictive model for post-surgical PE with 6 miRNAs: miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p and miR-140-3p (AUC = 0.78; 95% Confidence Interval (CI) [0.63, 0.94]) and another with cfDNA and myeloperoxidase as predictors (AUC = 0.71; 95%CI [0.52, 0.90]). Furthermore, we combined both types of markers and obtained a model with myeloperoxidase and miR-140-3p as predictors (AUC = 0.79; 95%CI [0.64, 0.94]). In meningioma patients we fitted and validated a predictive model with 6 miRNAs: miR-29a-3p, miR-660-5p, miR-331-3p, miR-126-5p, miR-23a-3p and miR-23b-3p (AUC = 0.69; 95%CI [0.52, 0.87]). All our models outperformed the Khorana score. This is the first study that analyzes the capability of plasma miRNAs and neutrophil activation markers to predict early post-surgical PE in glioma and meningioma patients. The estimation of the thrombotic risk before surgery may promote a tailored thromboprophylaxis in a selected group of high-risk patients, in order to minimize the incidence of PE and avoid bleedings.

PMID:32545233 | DOI:10.3390/cancers12061536

05:03

PubMed articles on: Cancer & VTE/PE

In vivo performance of gold nanoparticle-loaded absorbable inferior vena cava filters in a swine model

Huang SY, et al. Biomater Sci 2020.

 

ABSTRACT

PURPOSE: With the increasing interest in treatment decision-making based on risk prediction models, it is essential for clinicians to understand the steps in developing and interpreting such models.

METHODS: A retrospective registry of 20 Dutch hospitals with data on patients treated for castration-resistant prostate cancer was used to guide clinicians through the steps of developing a prediction model. The model of choice was the Cox proportional hazard model.

RESULTS: Using the exemplary dataset several essential steps in prediction modelling are discussed including: coding of predictors, missing values, interaction, model specification and performance. An advanced method for appropriate selection of main effects, e.g. Least Absolute Shrinkage and Selection Operator (LASSO) regression, is described. Furthermore, the assumptions of Cox proportional hazard model are discussed, and how to handle violations of the proportional hazard assumption using time-varying coefficients.

CONCLUSION: This study provides a comprehensive detailed guide to bridge the gap between the statistician and clinician, based on a large dataset of real-world patients treated for castration-resistant prostate cancer.

PMID:32556680 | DOI:10.1007/s00432-020-03286-8

05:03

PubMed articles on: Cancer & VTE/PE

Effect of chemotherapy and longitudinal analysis of circulating extracellular vesicle tissue factor activity in patients with pancreatic and colorectal cancer

Kasthuri RS, et al. Res Pract Thromb Haemost 2020.

ABSTRACT

INTRODUCTION: We conducted a longitudinal study in patients with pancreatic and colorectal cancer. We determined the effect of chemotherapy on extracellular vesicle tissue factor (EVTF) activity and the association of plasma EVTF activity with venous thromboembolism (VTE) and survival.

MATERIAL AND METHODS: We enrolled 13 patients with pancreatic and 22 patients with colorectal cancer. Plasma samples were collected during the 85-day study period. Patients were followed for 3 months after the study period. We recorded symptomatic VTE during the study period (3 months) or asymptomatic deep vein thrombosis detected by ultrasound at day 85. We measured EVTF activity before and after chemotherapy.

RESULTS AND CONCLUSIONS: In the pancreatic cancer group, 2 patients had elevated levels of EVTF activity. One of these patients developed symptomatic VTE and died, and the second patient did not have a VTE but died. Chemotherapy decreased EVTF activity in 2 pancreatic patients with high levels. In the colorectal cancer group, 4 patients developed VTE, but EVTF activity was not elevated in any patient and no patient died. We observed a borderline significant correlation between EVTF activity and D-dimer in the patients with pancreatic but not colorectal cancer. In this small descriptive study, 2 patients with pancreatic cancer had an elevated level of EVTF activity. Both patients died during the study period, and one had a VTE. Chemotherapy decreased EVTF activity in these patients. In contrast, elevated levels of EVTF activity were not observed in patients with colorectal cancer with or without VTE.

PMID:32548563 | PMC:PMC7292676 | DOI:10.1002/rth2.12317

05:03

PubMed articles on: Cardio-Oncology

Gender differences in quality of life in coronary artery disease patients with comorbidities undergoing coronary revascularization

Oreel TH, et al. PLoS One 2020.

ABSTRACT

In comparison to male patients with coronary artery disease, female patients suffer from more comorbidities, experience symptoms of coronary artery disease differently and report poorer health-related quality of life (HRQoL) after coronary revascularization. However, there is limited data on the impact of comorbidity burden on the recovery in HRQoL in female and male patients. We investigated the impact of comorbidity burden on the change in HRQoL following coronary revascularization in female patients versus male patients. 230 patients (60 female) with coronary artery disease were assessed before, and two weeks, three months and six months after coronary revascularization. Disease-specific HRQoL was measured with the Short-Form Seattle Angina Questionnaire. Physical and mental health was measured with the Short-Form Health Survey. Comorbidity burden was assessed by the total number of identified comorbidity conditions and by the Charlson comorbidity score. Linear mixed models were used to estimate the effects of time, gender and comorbidity burden on HRQoL. Whereas HRQoL improved after coronary revascularization in all patients, female patients reported poorer physical health and disease-specific HRQoL and their physical health improved more slowly than male patients. A higher comorbidity burden was related with poorer physical health and disease-specific HRQoL in male patients, but not in female patients. A higher comorbidity burden was associated with slower improvement in HRQoL for both female and male patients. Female patients reported poorer HRQoL and their physical health improved more slowly after coronary revascularization, irrespective of comorbidity burden. Higher comorbidity burden was associated with poorer physical health and disease-specific HRQoL in male patients only. Our results indicate that female and male patients recover differently after coronary revascularization. These findings highlight the importance of comorbidity- and gender-specific approaches for evaluating coronary artery disease and coronary revascularization procedures.

PMID:32555617 | PMC:PMC7299316 | DOI:10.1371/journal.pone.0234543

05:03

PubMed articles on: Cancer & VTE/PE

Direct oral anticoagulants compared to low-molecular-weight heparin for the treatment of cancer-associated thrombosis: Updated systematic review and meta-analysis of randomized controlled trials

Moik F, et al. Res Pract Thromb Haemost 2020.

ABSTRACT

BACKGROUND: Low-molecular-weight-heparins (LMWHs) have been established for the treatment of cancer-associated venous thromboembolism (VTE). Recently published randomized controlled trials (RCTs) have compared direct oral anticoagulants (DOACs) with LMWHs. The aim of this systematic review and meta-analysis was to evaluate efficacy and safety of DOACs versus LMWHs and update the evidence for treatment of VTE in cancer.

METHODS: Biomedical databases were screened for RCTs evaluating DOACs for cancer-associated VTE. Primary efficacy and safety outcomes of this meta-analysis were recurrent VTE and major bleeding at 6 months. Secondary outcomes comprised clinically relevant nonmajor bleeding (CRNMB), major gastrointestinal (GI) and genitourinary bleeding, mortality, fatal bleeding/pulmonary embolism, and treatment discontinuation rate. We performed prespecified subgroup analyses. Pooled relative risk (RR) and 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effect model.

RESULTS: We screened 759 articles and included 4 RCTs (n = 2894). DOACs significantly reduced recurrent VTEs compared to LMWHs (5.2% vs 8.2%; RR, 0.62 [95% CI, 0.43-0.91]), but were associated with a nonsignificant increase in major bleedings (4.3% vs 3.3%; RR, 1.31 [95% CI, 0.83-2.08]) and a significant increase in CRNMB (10.4% vs 6.4%; RR, 1.65 [95% CI, 1.19-2.28]). Mortality risks were comparable between groups (RR, 0.99 [95% CI, 0.83-1.18]). Preterm treatment discontinuation was less common with DOACs (RR, 0.88 [95% CI, 0.81-0.96]). Major bleeding was more frequent in patients with GI cancer treated with DOACs (RR, 2.30 [95% CI, 1.08-4.88]).

CONCLUSION: In patients with cancer-associated VTE, DOACs are more effective in preventing recurrent VTE compared to LMWH. However, risk of bleeding is increased with DOACs, especially in patients with GI cancer.

PMID:32548553 | PMC:PMC7292654 | DOI:10.1002/rth2.12359

05:03

PubMed articles on: Cardio-Oncology

Uncoupling DNA damage from chromatin damage to detoxify doxorubicin

Qiao X, et al. Proc Natl Acad Sci U S A 2020.