CSM

Q: What is Confined Space Medicine (CSM)?

Answer: Confined space medicine is a concept of providing medical treatment when victims can't be moved from the trauma scene mostly after mass casualty scenes such as earthquakes, building collapses, mines entrapment, fire, bomb blasts, etc. The focus stays on initial crush injury care and crush syndrome prevention. 

It requires special training. This training provides knowledge about the medical aspect and managing hazards like dust, temperature extremes, hazardous materials, poisonous gases, fire, explosions, secondary collapse, and wearing personal protective equipment (PPE). 

#trauma

References:

1. Petinaux B, Macintyre AG, Barbera JA. Confined space medicine and the medical management of complex rescues: a case series. Disaster Med Public Health Prep 2014; 8:20.

2. Jensen J, Thompson S. The Incident Command System: a literature review. Disasters 2016; 40:158.

Smoking and HP

Q: Smoking ____________ the risk of Hypersensitivity pneumonitis (HP)? (select one)

A) decreases

B) increases

Answer: A

This is one of the paradoxes of medicine. Hypersensitivity pneumonitis is also known as extrinsic allergic alveolitis. Interestingly, and hard to explain, cigarette smoking decreases the risk of HP. Smokers are less likely to develop different forms of HP, such as farmer's lungs, pigeon breeder's disease, HP-associated contaminated air conditioners, and Japanese summer-type HP. 

Said that once the disease is established, smoking turns it into a more chronic and severe course.

One possible explanation is smokers' diminished antibody responses to inhaled antigens despite similar exposure.

#pulmonary

References:

1. Arima K, Ando M, Ito K, et al. Effect of cigarette smoking on prevalence of summer-type hypersensitivity pneumonitis caused by Trichosporon cutaneum. Arch Environ Health 1992; 47:274.

2. McSharry C, Banham SW, Boyd G. Effect of cigarette smoking on the antibody response to inhaled antigens and the prevalence of extrinsic allergic alveolitis among pigeon breeders. Clin Allergy 1985; 15:487.

3. Ohtsuka Y, Munakata M, Tanimura K, et al. Smoking promotes insidious and chronic farmer's lung disease, and deteriorates the clinical outcome. Intern Med 1995; 34:966.

Botulinum for achalasia

Case: 58 years old male with known history of achalasia is admitted to ICU with aspiration pneumonia. Patient previously had refused surgical interventions for achalasia. Gastrointestinal (GI) service recommends botulinum toxin injection. Botulinum toxin therapy provides permanent cure for achalasia?

A) True

B) False

Answer: B

Achalasia can be cured or contained with various pharmacological and surgical interventions. The more definitive therapy are pneumatic dilation, surgical myotomy, or Peroral Endoscopic Myotomy (POEM). Botulinum toxin injection is a short-term procedure that provides relief for a few months. It has a high relapse rate. It can be repeated but makes other definite therapies difficult in the future.

Botulinum toxin is injected into the Lower Esophageal Sphincter (LES). It paralyzes the excitatory (acetylcholine-releasing) neurons and decreases the basal LES pressure. It makes esophageal emptying easy when esophageal pressures exceed the partially paralyzed LES.

#GI

References:

1. Khashab MA, Vela MF, Thosani N, et al. ASGE guideline on the management of achalasia. Gastrointest Endosc 2020; 91:213.

2. Campos GM, Vittinghoff E, Rabl C, et al. Endoscopic and surgical treatments for achalasia: a systematic review and meta-analysis. Ann Surg 2009; 249:45.

3. Smith CD, Stival A, Howell DL, Swafford V. Endoscopic therapy for achalasia before Heller myotomy results in worse outcomes than heller myotomy alone. Ann Surg 2006; 243:579.

What do hibernating bears have to do with deep venous thrombosis?

 "To better understand how bears avoid dangerous blood clotting, a pair of cardiologists at the Ludwig Maximilian University of Munich, Tobias Petzold and Manuela Thienel, teamed up with a Scandinavian team and other researchers to study hibernating brown bears in Sweden.

For two winters, the researchers trekked through the snow to dig out sleeping brown bears wearing GPS collars. They tranquilized 13 bears, took blood samples, then returned the bears to their dens to finish their winter naps. The following summers, they tracked the same bears and took more blood samples. Collaborators at the Max Planck Institute of Biochemistry looked for seasonal differences in the bears’ blood that might explain why it did not clot in the winter...

The researchers noticed a protein called HSP47 was abundant in the bears’ blood during the summer, but virtually disappeared in the winter, Thienel and her colleagues report...

Previous work by Jon Gibbins, a cell biologist at the University of Reading, in mice had revealed that in addition to other functions, this protein sits on the surface of blood platelets involved in clot formation. Working with mice bred to lack this protein, Gibbins and his colleagues determined that platelets with less HSP47 were less likely to attract and bind to infection-fighting white blood cells called neutrophils—a key step in clot formation."

Full article @ https://www.science.org/content/article/now-we-know-why-hibernating-bears-don-t-get-blood-clots

Clear liquid before surgery

Q: In enhanced recovery after surgery (ERAS), holding clear liquids 12 hours prior to surgery showed early recovery?

A) True

B) False

Answer: B

Although conventional practice asks patients to be NPO 10-12 hours prior to surgery, evidence in the literature for ERAS favors encouraging the consumption of clear liquids until two to four hours before general anesthesia. Most fasting guidelines from international anesthesia societies now favor this practice.

American Society of Anesthesiologists, 2017 guidelines favor 2 hours margin for clear liquids, excluding alcohol. In fact, chewing gum is allowed up until induction. Also, healthy adults are encouraged to drink carbohydrates containing clear liquids. These guidelines apply to healthy patients, not in labor and undergoing elective surgery.

#surgical-critical-care

References:

1. Practice Guidelines for Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration: Application to Healthy Patients Undergoing Elective Procedures: An Updated Report by the American Society of Anesthesiologists Task Force on Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration. Anesthesiology 2017; 126:376.

2. Joshi GP, Abdelmalak BB, Weigel WA, et al. 2023 American Society of Anesthesiologists Practice Guidelines for Preoperative Fasting: Carbohydrate-containing Clear Liquids with or without Protein, Chewing Gum, and Pediatric Fasting Duration-A Modular Update of the 2017 American Society of Anesthesiologists Practice Guidelines for Preoperative Fasting. Anesthesiology 2023; 138:132.

Post COVID pulmonary dysfunction

Q: 44 years old male is getting discharged from ICU to long-term care after recovery from COVID-19-induced respiratory failure. While writing discharge orders, emphasis on which one component may help the patient?

Answer: Enrollment in pulmonary rehabilitation program

Patients who go into "long-COVID" syndrome have some marked benefits from protocolized pulmonary rehabilitation programs. Fatigue and muscle weakness are some of the common symptoms of long-covid. Enrollment in such programs has been shown to improve Short Physical Performance Battery (SPPB) and the Barthel Index. At a functional level, it has shown significant improvement for patients who were unable to stand, rise from a chair, and walk at the start of the program.

6-8 weeks of such programs have been suggested.

#pulmonary

#COVID

References:

1. Zampogna E, Paneroni M, Belli S, et al. Pulmonary Rehabilitation in Patients Recovering from COVID-19. Respiration 2021; 100:416.

2. Liu K, Zhang W, Yang Y, et al. Respiratory rehabilitation in elderly patients with COVID-19: A randomized controlled study. Complement Ther Clin Pract 2020; 39:101166.

Anbx in pregnancy

Q: 24 years old female at 28 weeks gestation is admitted to ICU with urosepsis. Which of the following antibiotics should not be used? (select one)

A) Meropenem

B) Fosfomycin 

C) Nitrofurantoin 

D) Trimethoprim-sulfamethoxazole

E) Fluoroquinolones 

Answer: E

Ideally, fluoroquinolones should not be used in pregnancy (choice E).

Penicillins, cephalosporins, carbapenems (choice A), and fosfomycin (choice B) are considered safe in pregnancy.

Nitrofurantoin (choice C) can be used after the first trimester but may fail to achieve good concentration in renal tissues and may not be effective.

Trimethoprim-sulfamethoxazole (choice D) should also be avoided during the first trimester and in the near term. There is a potential risk of kernicterus in the near term.

#Ob-gyn

#ID

References:

1. Bookstaver PB, Bland CM, Griffin B, et al. A Review of Antibiotic Use in Pregnancy. Pharmacotherapy 2015; 35:1052.

2. Ailes EC, Gilboa SM, Gill SK, et al. Association between antibiotic use among pregnant women with urinary tract infections in the first trimester and birth defects, National Birth Defects Prevention Study 1997 to 2011. Birth Defects Res A Clin Mol Teratol 2016; 106:940.

3. Le J, Briggs GG, McKeown A, Bustillo G. Urinary tract infections during pregnancy. Ann Pharmacother 2004; 38:1692.

Indications - Colon Resection

Q: Colon resection for fulminant Clostridioides difficile colitis is considered? (select one)

A) a benign condition

B) a malignant condition

Answer: A

The objective of this question is to highlight a kind of a misnomer regarding colon resection. Any condition beside malignancy are described as benign disease irrespective of their intensity. It includes: crohn disease, colon polyps, colonic ischemia or trauma, fulminant Clostridioides difficile colitis and volvulus.

All malignant conditions fall into the malignant bucket including: malignant and premalignant colon lesions, appendiceal cancer, colonic carcinoid, colonic gastrointestinal stromal tumors (GISTs), and metastatic tumors

#surgical-critical-care

References:

1. Xynos E, Gouvas N, Triantopoulou C, Tekkis P, Vini L, Tzardi M, Boukovinas I, Androulakis N, Athanasiadis A, Christodoulou C, Chrysou E, Dervenis C, Emmanouilidis C, Georgiou P, Katopodi O, Kountourakis P, Makatsoris T, Papakostas P, Papamichael D, Pentheroudakis G, Pilpilidis I, Sgouros J, Vassiliou V, Xynogalos S, Ziras N, Karachaliou N, Zoras O, Agalianos C, Souglakos J; [the Executive Team on behalf of the Hellenic Society of Medical Oncology (HeSMO)]. Clinical practice guidelines for the surgical management of colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO. Ann Gastroenterol. 2016 Jan-Mar;29(1):3-17. PMID: 26752945; PMCID: PMC4700843.

2. Lieske B, Ahmad H. Colon Resection. [Updated 2022 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431079/

3. https://www.uptodate.com/contents/overview-of-colon-resection (last accessed March 30, 2023)  

Hemorrhoids and positive occult blood tests

Q: Hemorrhoids do not affect the prevalence of positive occult blood tests (OBT).

A) True

B) False

Answer: B

Interestingly, occult Gastrointestinal (GI) bleeding can be due to many causes but hemorrhoids rarely turn occult blood test positive. This is due to the fact that most hemorrhoidal bleeding has whole blood.

A positive occult blood test just guides a physician to the probability of underlying pathology. It can include colon cancer, esophagitis, peptic ulcers, gastritis, inflammatory bowel disease, vascular ectasias, portal hypertensive gastropathy, gastric antral vascular ectasias, GI stromal cell tumor, lymphoma, carcinoid, adenocarcinoma, or polyp.

Hemoptysis and epistaxis can also cause a positive OBT.

#GI

References:

1. van Turenhout ST, Oort FA, Terhaar sive Droste JS, et al. Hemorrhoids detected at colonoscopy: an infrequent cause of false-positive fecal immunochemical test results. Gastrointest Endosc 2012; 76:136.

2. Korkis AM, McDougall CJ. Rectal bleeding in patients less than 50 years of age. Dig Dis Sci 1995; 40:1520.

IV and oral acetaminophen

Q: Intravenous (IV) acetaminophen has better efficacy than oral acetaminophen for perioperative pain?

A) True

B) False

Answer: B

IV acetaminophen's only advantage is its quick onset of action within 5-10 minutes. Oral acetaminophen may take up to an hour for a proper analgesic effect. IV and oral acetaminophen have similar efficacy of analgesia to relieve perioperative pain.

Due to massive differences in cost, the oral form is preferred.

#pharmacology

#surgical-critical-care

Reference:

1. Jibril F, Sharaby S, Mohamed A, Wilby KJ. Intravenous versus Oral Acetaminophen for Pain: Systematic Review of Current Evidence to Support Clinical Decision-Making. Can J Hosp Pharm 2015; 68:238.

2. Plunkett A, Haley C, McCoart A, et al. A Preliminary Examination of the Comparative Efficacy of Intravenous vs Oral Acetaminophen in the Treatment of Perioperative Pain. Pain Med 2017; 18:2466.

3. Hickman SR, Mathieson KM, Bradford LM, et al. Randomized trial of oral versus intravenous acetaminophen for postoperative pain control. Am J Health Syst Pharm 2018; 75:367.

Types of amyloidosis

Q: Which amyloidosis occurs due to recurring inflammation in the body? (select one)

A) AL amyloid 

B) ATTR amyloid 

C) AA amyloidosis

D) Insulin amyloid

Answer: C

There are various 18 different types of systemic and 22 localized forms of amyloidosis. Immunoglobulin light chain (AL) and transthyretin (ATTR) are primary amyloidoses.

AL amyloid is caused by plasma cell dyscrasia (choice A).

ATTR amyloid is usually hereditary or may be associated with aging. It is very common to cause cardiomyopathy (choice B).

AA amyloidosis is a potential complication of chronic diseases with ongoing or recurring inflammation resulting in a high serum amyloid A protein, an acute phase reactant (Choice C).

There are many types of amyloidosis, such as dialysis-related amyloidosis, heritable amyloidoses, organ-specific amyloid, and insulin amyloid (choice D).

#amyloidosis

Reference:

Benson MD, Buxbaum JN, Eisenberg DS, et al. Amyloid nomenclature 2020: update and recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid 2020; 27:217.

CK, Myoglobin and Rhabdomyolysis

Q: In rhabdomyolysis, which appears first in the plasma? (select one)

A) Creatine Kinase (CK)

B) Myoglobin 

Answer: B

The important lesson in rhabdomyolysis is independently reading CK and myoglobin in plasma and urine.

Myoglobin has a short half-life of couple of hours. In contrast, CK has a half-life of one and a half days. Myoglobin is quickly metabolized to bilirubin. Myoglobin appears in the plasma before CK elevation and returns to normal within six to eight hours. In contrast, CK may continue to rise in plasma. CK may remain elevated despite no myoglobinuria. 

Clinically, this is important as pigmenturia may be missing in rhabdomyolysis if a load of myoglobin is insufficient or resolved or the patient receives medical treatment early in the course. 

By conventional definition, rhabdomyolysis is five times or more above the upper limit of normal.

#musculo-skeletal

#nephrology

References:

1. Giannoglou GD, Chatzizisis YS, Misirli G. The syndrome of rhabdomyolysis: Pathophysiology and diagnosis. Eur J Intern Med 2007; 18:90.

2. Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine (Baltimore) 1982; 61:141.

insensible water loss in vent patients

Q: Patients on invasive ventilator have_________ alveolar water losses? (select one)

A) decreased

B) increased

Answer: A

Unfortunately, with electronic medical records and automated data insertion in everyday progress notes, insensible water losses are frequently overlooked. Patients' four major sources of water loss are urine, skin, respiratory tract, and stool. 

Patients who are hyperventilating have higher alveolar water losses. Conversely, patients on ventilators inspire humidified air which is warmed to the body temperature. This decreases the alveolar water/insensible loss via the respiratory tract.

#water-balance

#pulmonary

References:

1. McNeil-Masuka J, Boyer TJ. Insensible Fluid Loss. [Updated 2022 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544219/

2. Jacob M, Chappell D, Hofmann-Kiefer K, Conzen P, Peter K, Rehm M. Determinanten des insensiblen Flüssigkeitsverlustes. Perspiratio, Proteinshift und endotheliale Glykokalyx [Determinants of insensible fluid loss. Perspiration, protein shift and endothelial glycocalyx]. Anaesthesist. 2007 Aug;56(8):747-58, 760-4. German. doi: 10.1007/s00101-007-1235-4. PMID: 17684711.

Falsely elevated international INRs

Q: What is the most common cause of falsely elevated international normalized ratio (INR)?

Answer: Heparin in the blood sample

The two major causes of falsely elevated INRs in ICU are:

1. The presence of heparin in the drawn blood sample, particularly in hospitalized patients, is the most common cause of falsely elevated INRs. It is important to draw blood samples from a peripheral vein. Drawing blood samples from central venous catheters (CVCs) or arterial lines (A-lines) in ICU can give false information. 

2. Second major cause of falsely elevated INRs is drawing less than the optimum quantity of blood. This provides a higher than normal ratio of citrate anticoagulant drawn plasma. 

Also, the presence of a lupus anticoagulant artificially prolongs the INR value.

#hematology

#lab-medicine

References:

1. Froom P, Barak M. Falsely elevated prothrombin international normalized ratio values. Am J Clin Pathol. 2010 Jul;134(1):86-9. doi: 10.1309/AJCPDKQV2UMO2FAB. PMID: 20551271.

2. Delate T, Witt DM, Jones JR, Bhardwaja B, Senser M. Falsely elevated international normalized ratio values in patients undergoing anticoagulation therapy: a descriptive evaluation. Chest. 2007 Mar;131(3):816-822. doi: 10.1378/chest.06-2200. PMID: 17356098.

WBC and MI

Q: White blood cell (WBC) count after an acute ST-elevation myocardial infarction (MI) correlate with mortality? 

A) True

B) False

Answer: A

Relatively less highlighted, but high WBC count correlates with short- and long-term mortality after an acute ST elevation MI. A high WBC count is a marker of inflammation and predicts the extent of infarction. The higher the WBC count, the higher the risk of 30 days mortality, especially in older patients. 

This risk becomes significant once the WBC count goes above 15,000/µL. Unfortunately, this risk persists for months, depending on the WBC count at the time of the event.

#cardiology

References:

1. Madjid M, Awan I, Willerson JT, Casscells SW. Leukocyte count and coronary heart disease: implications for risk assessment. J Am Coll Cardiol 2004; 44:1945.

2. Cannon CP, McCabe CH, Wilcox RG, et al. Association of white blood cell count with increased mortality in acute myocardial infarction and unstable angina pectoris. OPUS-TIMI 16 Investigators. Am J Cardiol 2001; 87:636.

3. Barron HV, Harr SD, Radford MJ, et al. The association between white blood cell count and acute myocardial infarction mortality in patients > or =65 years of age: findings from the cooperative cardiovascular project. J Am Coll Cardiol 2001; 38:1654.

4. Patel MR, Mahaffey KW, Armstrong PW, et al. Prognostic usefulness of white blood cell count and temperature in acute myocardial infarction (from the CARDINAL Trial). Am J Cardiol 2005; 95:614.

A note on paralytic rabies

Although less common, few patients who contract rabies develop an ascending paralysis, very much like of Guillain-Barré syndrome. History and exposure to animal is of paramount importance to distinguish between two. Preceded by prodromal symptoms patient develop a flaccid paralysis. Clinical exam is important as paralysis is more pronounced in the bitten limb. It can ascends either symmetrically or asymmetrically accompanied by possible fasciculations, and loss of deep tendon and plantar reflexes. 

Simultaneously patient complain of headache, pain in the bitten muscles, and mild sensory disturbance. Nuchal rigidity and cranial nerve palsies may be present. Ascending paralysis culminates into dense paraplegia, loss of sphincter tone and fatal paralysis of the muscles of deglutition and respiration.

Interestingly, in contrast to conventional form of rabies hydrophobia is unusual.

#neurology

#ID

References:

1. Hemachudha T, Wacharapluesadee S, Mitrabhakdi E, Wilde H, Morimoto K, Lewis RA. Pathophysiology of human paralytic rabies. J Neurovirol. 2005 Feb;11(1):93-100. doi: 10.1080/13550280590900409. PMID: 15804967.

2. Kalita J, Bhoi SK, Bastia JK, Lashkar S, Mahadevan A, Misra UK. Paralytic rabies: MRI findings and review of literature. Neurol India. 2014 Nov-Dec;62(6):662-4. doi: 10.4103/0028-3886.149394. PMID: 25591681.

3. Mitrabhakdi E, Shuangshoti S, Wannakrairot P, Lewis RA, Susuki K, Laothamatas J, Hemachudha T. Difference in neuropathogenetic mechanisms in human furious and paralytic rabies. J Neurol Sci. 2005 Nov 15;238(1-2):3-10. doi: 10.1016/j.jns.2005.05.004. Epub 2005 Oct 14. PMID: 16226769.

4. Chopra JS, Banerjee AK, Murthy JM, Pal SR. Paralytic rabies: a clinico-pathological study. Brain. 1980 Dec;103(4):789-802. doi: 10.1093/brain/103.4.789. PMID: 7437890.

Ca and acid-base

Q: Acidosis __________ the bonding of albumin-calcium complex? (select one)

A) enhances

B) weakens

Answer: B

The serum calcium level measurement depends on the albumin-calcium complex's equilibrium constant. Acid-base disbalances disturb calcium-albumin bonding. Acidosis reduces this bonding, and alkalosis enhances it. 

Clinical significance: This is critically important in ICU, where the patient's acid-base level varies widely. Although formulae are available to adjust calcium per albumin, these formulae are not applicable in such situations. This is due to the fact that overall calcium or albumin level may be constant. Ideally, the ionized calcium should be measured.

#acid-base

#electrolytes

References:

1. Dickerson RN, Alexander KH, Minard G, et al. Accuracy of methods to estimate ionized and "corrected" serum calcium concentrations in critically ill multiple trauma patients receiving specialized nutrition support. JPEN J Parenter Enteral Nutr 2004; 28:133.

2. Schafer AL, Shoback DM. Hypocalcemia: Diagnosis and Treatment. [Updated 2016 Jan 3]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279022/

Sotalol metabolism

Q: Sotalol should be used with caution in patients with? (select one)

A) liver insufficiency

B) renal insufficiency

Answer: B

Sotalol is unique because it gets 100% absorbed, is not metabolized, and has 100% bioavailability - without any significant effect due to age or food. 

It has no first-pass effect and is excreted exclusively via kidneys. The dosing interval must be modified according to creatinine clearance and glomerular filtration rate (GFR).

#pharmacology

References:

1. Antonaccio MJ, Gomoll A. Pharmacology, pharmacodynamics and pharmacokinetics of sotalol. Am J Cardiol 1990; 65:12A.

2. Rizza C, Valderrabano M, Singh BN. Recurrent Torsades de Pointes After Sotalol Therapy for Symptomatic Paroxysmal Atrial Fibrillation in a Patient with End-Stage Renal Disease. J Cardiovasc Pharmacol Ther 1999; 4:129.

leucoreduction

Q: Leukoreduction in transfused blood products is performed? (select one)

A) at the time of blood collection

B) at the end of storage/delivery

Answer: A

Leukoreduction is in simple words filtering out white blood cells using an in-line filter. It is done at the time of blood collection. It is also called "pre-storage leukoreduction." The step helps in decreasing febrile nonhemolytic transfusion reactions (FNHTRs). Moreover, it also decreases the risk of cytomegalovirus (CMV) infection. 

#blood-bank

#hematology

References:

1. Bianchi M, Vaglio S, Pupella S, Marano G, Facco G, Liumbruno GM, Grazzini G. Leucoreduction of blood components: an effective way to increase blood safety? Blood Transfus. 2016 May;14(2):214-27. doi: 10.2450/2015.0154-15. Epub 2015 Dec 16. PMID: 26710353; PMCID: PMC4918553.

2. Bilgin YM, van de Watering LM, Brand A. Clinical effects of leucoreduction of blood transfusions. Neth J Med. 2011 Oct;69(10):441-50. PMID: 22058263.

doripenem warning

Q: FDA has a black box warning for Doripenem about increased mortality rates in which patient population? (select one)

A) Ventilator-associated bacterial pneumonia

B) Dialysis patients with sepsis

Answer: A

Doripenem has excellent clinical efficacy in complicated urinary tract and intra-abdominal infections. It has also shown better in vitro activity against P. aeruginosa than meropenem. Said that the US Food and Drug Administration (FDA) has issued in 2014 about increased mortality in patients with ventilator-associated bacterial pneumonia. It should be noted that this warning was based only on one trial which was stopped due to safety reasons. No further trial was run, and warning still stands valid. 

Critics believed adjunctive use of aminoglycosides may have influenced the results.

#pharmacology

References:

1. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-approves-label-changes-antibacterial-doribax-doripenem-describing (Accessed on March 29, 2023).

2. Kollef MH, Chastre J, Clavel M, et al. A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia. Crit Care 2012; 16:R218.

KS

Q: Kaposi Sarcoma is usually very tender?

A) True

B) False

Answer: B

The most common form of KS is cutaneous. Common sites are lower extremities, nose, face, oral mucosa, and genitalia. They are usually elliptical in shape. Classically, they are arranged in a linear fashion along the skin tension lines. Also, frequently they are distributed symmetrically. 

KS are neither tender nor pruritic. Also, they do not cause necrosis of either overlying skin or underlying tissues. It can be of variety of colors such as pink, red, purple and brown. They can be of various sizes. Clinicians should be mindful of a varieties of KS, where they can be plaque-like, especially on the soles and thighs, or exophytic and fungating with breakdown of overlying skin.

Differential diagnosis includes purpura, hematomas, angiomas, dermatofibromas, and nevi. 

#oncology

#HIV

#dermatology

References:

1. Cesarman E, Damania B, Krown SE, Martin J, Bower M, Whitby D. Kaposi sarcoma. Nat Rev Dis Primers. 2019 Jan 31;5(1):9. doi: 10.1038/s41572-019-0060-9. PMID: 30705286; PMCID: PMC6685213.

2. Bishop BN, Lynch DT. Kaposi Sarcoma. 2022 Jun 11. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 30521260.

Two generations of 5HT3 receptor antagonists

Q; 44 years old male is admitted to ICU with severe hypovolemia due to chemotherapy-induced vomiting. Which of the following is the second-generation 5-HT3 receptor antagonist? (select one)

A) dolasetron

B) ondansetron

C) ramosetron

D) tropisetron

E) palonosetron

Answer: E

This question aims to introduce two generations of 5-HT3 receptor antagonists, which are used in severe nausea and vomiting, particularly in oncology patients. 5HT3 receptor antagonists are 5hydroxytryptamine receptor antagonists, also known as serotonin blockers or receptor antagonists.

The most common 5HT3 receptor antagonists are first-generation, such as azasetron, dolasetron, granisetron, ondansetron, ramosetron, and tropisetron. They particularly have an effect on QTc and may induce arrhythmia.

Palonosetron is the only second-generation agent available in the USA. It has 30- to 100-fold higher affinity for 5-HT3 receptor with a marked longer half-life of up to 40 hours. Moreover, QTc prolongation is very unlikely. Also, when combined with glucocorticoids, it effectively on delays emesis.

Updated antiemetic guidelines from the National Comprehensive Cancer Network (NCCN) recommend palonosetron as the preferred 5-HT3 antagonist for patients who receive moderately emetogenic chemotherapy.

Oral and intravenous (IV) forms have similar efficacy. The dose is 0.5 mg. 

#pharmacology

#oncology

References:

1. Likun Z, Xiang J, Yi B, et al. A systematic review and meta-analysis of intravenous palonosetron in the prevention of chemotherapy-induced nausea and vomiting in adults. Oncologist 2011; 16:207.

2. Saito M, Aogi K, Sekine I, et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol 2009; 10:115.

3. Gonullu G, Demircan S, Demirag MK, et al. Electrocardiographic findings of palonosetron in cancer patients. Support Care Cancer 2012; 20:1435.

4. Gralla R, Lichinitser M, Van Der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 2003; 14:1570.

serotonin modulators

Q: Trazodone is an atypical antidepressant?

A) True

B) False

Answer: B

The objective of this question is to bring to light a district group of centrally acting drugs called serotonin modulators. Drugs in this group are distinct from selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, tricyclics, and monoamine oxidase inhibitors (MAOIs). 

Serotonin modulators act as antagonists as well as agonists at postsynaptic serotonin receptors. By this dual effect, they inhibit reuptake of postsynaptic serotonin, with minimal effect upon norepinephrine reuptake.

Drugs in this group includes: Trazodone, Nefazodone, Vilazodone, and Vortioxetine. 

#pharmacology

#psychiatry

References:

1. Mishra A, Sarangi SC, Maiti R, Sood M, Reeta KH. Efficacy and Safety of Adjunctive Serotonin-Dopamine Activity Modulators in Major Depression: A Meta-Analysis of Randomized Controlled Trials. J Clin Pharmacol. 2022 Jun;62(6):721-732. doi: 10.1002/jcph.2022. Epub 2022 Feb 8. PMID: 34967946.

2. Morrissette DA, Stahl SM. Modulating the serotonin system in the treatment of major depressive disorder. CNS Spectr. 2014 Dec;19 Suppl 1:57-67; quiz 54-7, 68. doi: 10.1017/S1092852914000613. Erratum in: CNS Spectr. 2015 Aug;20(4):452-3. PMID: 25544378.

GI regimen in ICU

Q: Polyethylene glycol (PEG), lactulose, and sorbitol are? (select one)

A) Hyper-osmolar laxatives

B) Hypo-osmolar laxatives 

Answer: A

PEG, lactulose and sorbitol are frequently used in ICU for gastrointestinal regimen protocols, particularly when narcotics are in use. They works via their hyperosmolar composition. PEG has the advantage that it does not cause gas or bloating.

Psyllium, methylcellulose, and calcium polycarbophil are bulk forming laxatives due their fiber makeup. 

Magnesium hydroxide (Milk of Magnesia) and magnesium citrate are called saline laxatives and worked more like hyperosmolar laxatives.

Senna  and bisacodyl are stimulants.

#GI

References:

1. Paré P, Fedorak RN. Systematic review of stimulant and nonstimulant laxatives for the treatment of functional constipation. Can J Gastroenterol Hepatol. 2014 Nov;28(10):549-57. doi: 10.1155/2014/631740. PMID: 25390617; PMCID: PMC4234355.

2. Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut. 2011 Feb;60(2):209-18. doi: 10.1136/gut.2010.227132. PMID: 21205879.

Folate in depression

Q: Folate is a useful adjuvant treatment in major depressive disorder?

A) True

B) False

Answer: B

Many adjuvant treatments have been described for treatment-refractory depression but failed to stand credibility in trials. These include

• Buspirone
• Cannabis
• Folate
• Inositol 
• Lamotrigine
• Magnesium
• Memantine 
• Metyrapone
• Pindolol
• Pioglitazone
• Riluzole 
• Testosterone for females 

#psychiatry

Reference -

Michael Thase, K Ryan Connolly - https://www.uptodate.com/contents/unipolar-depression-in-adults-management-of-highly-resistant-refractory-depression - © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

perimesencephalic subarachnoid hemmorhage (PM-NASAH)

Q: What is perimesencephalic subarachnoid hemorrhage?

Answer: Perimesencephalic subarachnoid hemorrhage is a subtype of nonaneurysmal SAH (NASAH). It is not very common, but clinical identification is important as these patients usually have a benign course and do well. They may require different management strategies. These patients have a characteristic pattern of localized blood on computed tomography (CT) and have normal cerebral angiography. 

The initial clinical presentation may be the same, but rebleeding and vasospasm are less common. The efficacy of nimodipine is not very clear but is still a part of the standard of care.

#neurology

#neuro-surgery

References:

1. Rinkel GJ, Wijdicks EF, Hasan D, et al. Outcome in patients with subarachnoid haemorrhage and negative angiography according to pattern of haemorrhage on computed tomography. Lancet 1991; 338:964.

2. Flaherty ML, Haverbusch M, Kissela B, et al. Perimesencephalic subarachnoid hemorrhage: incidence, risk factors, and outcome. J Stroke Cerebrovasc Dis 2005; 14:267.

3. Mensing LA, Vergouwen MDI, Laban KG, et al. Perimesencephalic Hemorrhage: A Review of Epidemiology, Risk Factors, Presumed Cause, Clinical Course, and Outcome. Stroke 2018; 49:1363.

MS in thyroid storm

Q: Altered mental status is statistically associated with mortality in thyroid storm?

A) Yes

B) No

Answer: Yes

Not all patients present with classic symptoms of thyroid storm, particularly if they are already on beta-blocker (BB) or anti-thyroid medication. They may already be in "compensated hyperthyroidism." These patients may just present with altered mental status, which is found to be statistically associated with mortality in thyroid storms. Other factors associated with high mortality are older age, mechanical ventilation, and discontinuation of anti-thyroid medication or BB.

Non-compensated thyroid storm patients may present with high grades ever. Fever of 104 to 106°F is common in thyroid storms, besides nausea, vomiting, diarrhea, abdominal pain, jaundice, lid lag, tremor, and warm moist skin.

#endocrinology

#physical-exam

References:

1. Swee du S, Chng CL, Lim A. Clinical characteristics and outcome of thyroid storm: a case series and review of neuropsychiatric derangements in thyrotoxicosis. Endocr Pract 2015; 21:182.

2. Angell TE, Lechner MG, Nguyen CT, et al. Clinical features and hospital outcomes in thyroid storm: a retrospective cohort study. J Clin Endocrinol Metab 2015; 100:451.

3. Ono Y, Ono S, Yasunaga H, et al. Factors Associated With Mortality of Thyroid Storm: Analysis Using a National Inpatient Database in Japan. Medicine (Baltimore) 2016; 95:e2848.