Friday, April 16, 2021

folate, folic acid, folinic acid, and 5-methyltetrahydrofolate

 Q: What is the difference between folate, folic acid, folinic acid, and 5-methyltetrahydrofolate (5-MTHF)? 

 Answer: Although folate and folic acid are used interchangeably, technically they are different terms. 

  • Folate in actuality is vitamin B-9 and comes naturally from plant-based foods and fortified grains.  
  • Folic acid is the synthetic oxidized, water-soluble form.
  • Folinic acid and 5-MTHF are also naturally occurring, and are reduced forms of folate. 

 Clinical implications: 

1. Folic acid, folinic acid, and 5-MTHF are all effective in treating folate deficiency. 

2. Folinic acid has a special clinical advantage in preventing toxicities of methotrexate but potentiating the cytotoxicity of fluorouracil (chemotherapy agent).

#pharmacology


References:

1. Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica 2014; 44:480. 

2. Kelly GS. Folates: supplemental forms and therapeutic applications. Altern Med Rev 1998; 3:208.

Thursday, April 15, 2021

AUB and SIS

 Q: 48 years old female is admitted to ICU with severe abnormal uterine bleeding (AUB). Ob-Gyn service is called while ICU service worked on hemodynamic stabilization. At the bedside service requests for sterile saline. What is the purpose of sterile saline in Ob-Gyn examination and in AUB?

Answer: Instilling sterile saline directly into the uterine cavity via the cervix during ultrasound of the uterus enhances endometrial visualization. It helps in delineate different endometrial pathologies like polyps, hyperplasia, cancer, leiomyomas, or adhesions. A recent version of Saline Infusion Sonography (SIS) is to replace saline with hydroxyethylcellulose gel, which provides a relatively more stable filling of the uterine cavity and does not require continuous installation. In severe AUB a balloon tamponade can be used with saline infusion to control heavy bleeding. 

Although SIS is a very safe procedure in experienced hands there is always a concern about disseminating infection and carcinoma. SIS may give rise to false diagnoses due to blood clots, debris, mucus plugs, and other artifacts.

#Ob-Gyn


References:

1. American College of Obstetricians and Gynecologists. ACOG Technology Assessment in Obstetrics and Gynecology No. 5: sonohysterography. Obstet Gynecol 2008; 112:1467. 

2. Guideline developed in collaboration with the American College of Radiology, American College of Obstetricians and Gynecologists, Society of Radiologists in Ultrasound. AIUM Practice Guideline for the Performance of Sonohysterography. J Ultrasound Med 2015; 34:1.

3. Chawla I, Tripathi S, Vohra P, Singh P. To Evaluate the Accuracy of Saline Infusion Sonohysterography (SIS) for Evaluation of Uterine Cavity Abnormalities in Patients with Abnormal Uterine Bleeding. J Obstet Gynaecol India. 2014;64(3):197-201. doi:10.1007/s13224-013-0501-4 

4. Alcázar JL, Errasti T, Zornoza A. Saline infusion sonohysterography in endometrial cancer: assessment of malignant cells dissemination risk. Acta Obstet Gynecol Scand 2000; 79:321.

Wednesday, April 14, 2021

How Linezolid works in anthrax?

 Q: How Linezolid works in anthrax?

Answer: Linezolid has a fascinating mechanism of action in infections with Bacillus anthracis. Although so far it has been mostly demonstrated in vitro it has been proposed as a better treatment option in Anthrax. It abolishes the toxin production 100 percent and reduces the sporulation in Bacillus anthracis. 

Linezolid was found superior to ciprofloxacin, which is so far considered the standard of treatment in Bacillus anthracis (reference # 3)

#ID


References:

1. Head BM, Alfa M, Sitar DS, et al. In vitro evaluation of the effect of linezolid and levofloxacin on Bacillus anthracis toxin production, spore formation and cell growth. J Antimicrob Chemother 2017; 72:417. 

2. Hendricks KA, Wright ME, Shadomy SV, et al. Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014; 20. 

3. Louie A, Vanscoy BD, Heine HS 3rd, Liu W, Abshire T, Holman K, Kulawy R, Brown DL, Drusano GL. Differential effects of linezolid and ciprofloxacin on toxin production by Bacillus anthracis in an in vitro pharmacodynamic system. Antimicrob Agents Chemother. 2012 Jan;56(1):513-7. doi: 10.1128/AAC.05724-11. Epub 2011 Nov 7. PMID: 22064542; PMCID: PMC3256020.

Tuesday, April 13, 2021

CHL and B symptoms

 Q: Which of the following is NOT considered a part of B symptoms in Classic Hodgkins Lymphoma (CHL)? - select one

A) Fever 

 B) Sweats 

 C) Weight loss 

 D) Pruritus 


 Answer:

It should be understood that B symptoms have a formal definition in Lugano classification. It has three components with its own defined delineations. 

1. Fever should be persistent and above  38°C (>100.4°F). There is a variation of fever known as Pel-Ebstein fever that may be present. This variation of fever cyclically increases and decreases over a period of one to two weeks. In most cases, the patient complains of subjective fever more in the evening time.

2. Sweats should be described by the patient as drenching night sweats 

3. Weight loss should not be explained by any other means and should be more than 10 percent of actual body weight over the past six months.

Pruritus (choice D) though is not considered as a B symptom but has a high diagnostic value. In some patients, it precedes by many months before an actual diagnosis is made. It is usually generalized and can be severe enough to cause intense scratching and excoriations. 

#oncology


References:

1. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; 32:3059.

2. Good GR, DiNubile MJ. Images in clinical medicine. Cyclic fever in Hodgkin's disease (Pel-Ebstein fever). N Engl J Med 1995; 332:436. 

3. Gobbi PG, Cavalli C, Gendarini A, et al. Reevaluation of prognostic significance of symptoms in Hodgkin's disease. Cancer 1985; 56:2874

Monday, April 12, 2021

COVID and GI

 Q: In patients with inflammatory bowel disease (IBD), use of which of the following is found to have increased risk of COVID-19? (select one) 

 A) glucocorticoids 

B) anti-TNF therapy 


 Answer:

Overall patients with IBD have found to have no higher risk than the general population to acquire COVID-19, although patients on active treatment may have higher risk. Surprisingly, patients on glucocorticoids are found to have higher risk than patients on anti-TNF therapy (TNF = Tumor necrosis Factor). 

The gastrointestinal (GI) symptoms in COVID are due to the presence of widely expressed angiotensin-converting enzyme 2 (ACE2) receptors in the intestine. They are most prevalent in the cytoplasm of gastric cells, intestinal epithelial cells, and the cilia of glandular epithelial cells.

Caution: Literature on COVID-19 is still evolving.


#COVID

#GI


References:

1. Norsa L, Indriolo A, Sansotta N, et al. Uneventful Course in Patients With Inflammatory Bowel Disease During the Severe Acute Respiratory Syndrome Coronavirus 2 Outbreak in Northern Italy. Gastroenterology 2020; 159:371. 

2. Rubin DT, Feuerstein JD, Wang AY, Cohen RD. AGA Clinical Practice Update on Management of Inflammatory Bowel Disease During the COVID-19 Pandemic: Expert Commentary. Gastroenterology 2020; 159:350. 

3.  Brenner EJ, Ungaro RC, Gearry RB, et al. Corticosteroids, But Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry. Gastroenterology 2020; 159:481.

Sunday, April 11, 2021

Radiology in NSTIs

 Q: Due to gas formation in tissues which is the best diagnostic modality in necrotizing soft tissue infections (NSTIs)? (select one)

A) CT scan

B) MRI

C) Ultrasound


Answer: A

Though MRI and ultrasound can be performed in NSTIs, they are not as reliable to delineate surgical demarcation as a CT scan. MRI is oversensitive and cannot distinguish well between necrotizing cellulitis and deeper infection. Ultrasound can be used due to the presence of gas but so far evidence for its use is not very supportive. 

CT scan can reliably show gas presence in soft tissues, collection of fluid, heterogeneity of tissue enhancement, and inflammatory changes.

#surgical-critical-care

#radiology


References:

1. Zacharias N, Velmahos GC, Salama A, et al. Diagnosis of necrotizing soft tissue infections by computed tomography. Arch Surg 2010; 145:452. 

2. Schmid MR, Kossmann T, Duewell S. Differentiation of necrotizing fasciitis and cellulitis using MR imaging. AJR Am J Roentgenol 1998; 170:615.

Saturday, April 10, 2021

Acute flare of gout in ICU

 Q: 55 years old male with brittle diabetes and recent GI bleed is recovering from Diabetes Keo Acidosis (DKA) in ICU. Patient developed an acute flare of his gout. Patient uses colchicine as prophylaxis at home. Can colchicine be used to control the flare of gout?

A) Yes

B) No


Answer: A

Although glucocorticoids or NSAIDs are preferred to control acute gout in ICU, many patients may not be a candidate for either like our patient in the above question. In such cases, colchicine can be used. Colchicine is most effective if taken early in the course. 

Said that care should be taken as overdosing on colchicine is common and interaction/toxicity is common due to various commonly used drugs in ICU. 

The maximum dose is 1.8 mg in a divided dose on day one of the flare.

#rheumatology 


Reference:

1. Engel B, Just J, Bleckwenn M, Weckbecker K. Treatment Options for Gout. Dtsch Arztebl Int. 2017;114(13):215-222. doi:10.3238/arztebl.2017.0215

Friday, April 9, 2021

acute prostatis

 Q: 34 years old male with history of diabetes mellitus is transferred to ICU from the medical ward due to septic shock. Patient was admitted to hospital two days prior to transfer with acute prostatitis with an abscess formation. Which of the following part of the management may have led to septic shock in this patient? (select one)

A) failure to add a second antibiotic

B) failure of immediate surgical drainage

C) insertion of foley catheter

D) failure to do gram-stain of urine


Answer: C

The most common entry of infection in a susceptible male with acute severe prostatitis is through the urethra. Insertion of foley catheter in such an inflamed and infected urethra may lead to septic shock and possible rupture of the abscess. A suprapubic catheter is preferred.

Monotherapy with quinolone is usually sufficient in acute severe prostatis (choice A) although aminoglycoside may be added.

Emergent surgical drainage is not required but should be considered if antibiotics failed to resolve the abscess (choice B).

Gram-stains and cultures should be carried out as part of treatment but with the initiation of broad-spectrum antibiotics failure to do so should not cause septic shock by itself (choice D).

#ID

#urology


References:

1. Davis NG, Silberman M. Bacterial Acute Prostatitis. 2021 Jan 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 29083799.

2. Coker TJ, Dierfeldt DM. Acute Bacterial Prostatitis: Diagnosis and Management. Am Fam Physician. 2016 Jan 15;93(2):114-20. PMID: 26926407.

Thursday, April 8, 2021

SSZ MOA

 Q:  How Sulfasalazine (SSZ) works to be used in the management of two different diseases? 

Answer: SSZ is a unique drug that is used in two very different diseases via its route of elimination. It goes through a very interesting roller coaster ride after its oral ingestion. SSZ is a combination (inactive prodrug) of two compounds - 5-aminosalicylic acid (5-ASA) and sulfapyridine. 5-ASA helps in inflammatory bowel disease and sulfapyridine is used as a disease-modifying antirheumatic drug (DMARD). 

About one-third of SSZ absorbed by the small bowel and returned back intact via enterohepatic circulation into the bile. And from here most of the SSZ reaches the large intestine. SSZ needs coliform bacteria in the colon to be effective. Azoreductase is the enzyme that comes from the bacteria and breaks SSZ into its two compounds 5-ASA and sulfapyridine. 

5-ASA gets excreted in the feces making it very useful in the treatment of inflammatory bowel disease. Sulfapyridine is a DMARD. Sulfapyridine gets metabolized in the liver.

#pharmacology


References:

1. Box SA, Pullar T. Sulphasalazine in the treatment of rheumatoid arthritis. Br J Rheumatol 1997; 36:382.

2. Smedegård G, Björk J. Sulphasalazine: mechanism of action in rheumatoid arthritis. Br J Rheumatol 1995; 34 Suppl 2:7.

3. Das KM. Sulfasalazine therapy in inflammatory bowel disease. Gastroenterol Clin North Am. 1989 Mar;18(1):1-20. PMID: 2563989.

Wednesday, April 7, 2021

Severe hyperthyroidism in pregnancy

 Q: 27 years old 20 weeks pregnant female never been under clinical care is admitted to ICU with severe hyperthyroidism. All of the following can be parts of management EXCEPT?

A) Thionamides 

B) Beta-blockers 

C) Thyroidectomy

D) Plasmapheresis 

E) Radioiodine


Answer: E

Pregnancy presents special challenges in hyperthyroidism, particularly in an acute situation. One of the objectives of this question is to introduce the readers the use of plasmapheresis (choice D) in an acutely decompensating pregnant female with hyperthyroidism.

Thionamides (choice A) continues to be the mainstay of severe hyperthyroidism in pregnancy. When it comes to B-blockers (choice B), it should be remembered that atenolol is not recommended in pregnant patients, though metoprolol or propranolol can be used. Thyroidectomy (choice C) is reserved for rare cases like females who are not candidates for thionamides treatment.

Radioiodine (choice E) is absolutely contraindicated in pregnancy.

#ob-gyn
#endocrine


References:

1. De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97:2543. 

2. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016; 26:1343. 

3. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid 2017; 27:315. 

4. Adali E, Yildizhan R, Kolusari A, et al. The use of plasmapheresis for rapid hormonal control in severe hyperthyroidism caused by a partial molar pregnancy. Arch Gynecol Obstet 2009; 279:569. 

5. Stoffer SS, Hamburger JI. Inadvertent 131I therapy for hyperthyroidism in the first trimester of pregnancy. J Nucl Med 1976; 17:146.

Tuesday, April 6, 2021

VBG in ICU

 Q: Which venous blood gas (VBG) is preferable? (select one)

A) Central venous 

 B) Peripheral venous


Answer: A

In ICUs arterial blood gas (ABG) is preferred. During hemodynamic instability the discrepancy between ABG and VBG becomes significantly high and VBG cannot be relied upon. In shock state, the difference between mixed venous (SvO2) and arterial PCO2 increased by three times. 

Said that, in otherwise hemodynamically stable patients, VBG can be utilized. If a central venous catheter (CVC) (central line) is present VBG should be obtained from it. This is due to the fact that during normal hemodynamics HCO3 tends to be the same in ABG and CVC-VBG. In peripheral VBG, HCO3 is about 2-3 meq/L higher. Moreover, inappropriate use of a tourniquet during peripheral blood draw can make VBG unreliable due to transient local ischemia.

#acid-base


References:

1. Malinoski DJ, Todd SR, Slone S, et al. Correlation of central venous and arterial blood gas measurements in mechanically ventilated trauma patients. Arch Surg 2005; 140:1122. 

2. Walkey AJ, Farber HW, O'Donnell C, et al. The accuracy of the central venous blood gas for acid-base monitoring. J Intensive Care Med 2010; 25:104.

Monday, April 5, 2021

acute dysphagia

Q: 74 years old male while recovering from community-acquired pneumonia in ICU complained of food stuck in his esophagus at mid-chest (acute dysphagia). There is no shortness of breath and saturation stayed 100%. Which drug can be tried to relieve acute dysphagia before emergent endoscopy is called?


Answer: Glucagon

Intravenous glucagon relaxes the lower esophageal sphincter. This may prompt the food to pass in the stomach. The dose is 0.5 to 1-mg once. Patient may experience transient nausea. 

#GI


Reference:

Colon V, Grade A, Pulliam G, et al. Effect of doses of glucagon used to treat food impaction on esophageal motor function of normal subjects. Dysphagia 1999; 14:27.

Sunday, April 4, 2021

KS and steroid

 Q: Extent of Kaposi Sarcoma (KS) can be controlled with the maintenance of low dose steroid? 

 A) True 

B) False 


 Answer: B

The objective of the above question is to highlight the inverse relationship between steroids and KS. Steroids tend to worsen KS and weaning/withdrawal of steroid is associated with regression of KS lesions. 

In immunocompromised patients, there is a frequent need to use steroids such as during PJP treatment in AIDS patients. The risk of KS or proliferation of existing KS lesions should be kept in mind if steroids are instituted in immunocompromised patients such as AIDS, post-transplant, autoimmune and lymphoproliferative diseases.

#oncology


References:

1. Trattner A, Hodak E, David M, Sandbank M. The appearance of Kaposi sarcoma during corticosteroid therapy. Cancer 1993; 72:1779. 

2. Gill PS, Loureiro C, Bernstein-Singer M, et al. Clinical effect of glucocorticoids on Kaposi sarcoma related to the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1989; 110:937.

Saturday, April 3, 2021

B-blockers selectivity

 Q: Which of the following is a selective beta-1 adrenergic blocker? (select one)

A) atenolol 

B) propranolol


Answer: 

Atenolol being a selective beta-1 adrenergic blocker can be alternatively used where beta-blockers can not be used due to the effect on B--2 receptors such as asthma or bronchospasm. One of the drawbacks of atenolol is that its efficacy goes down at a higher dose i.e., above 100 mg per day. 

It is a drug with decades of experience and uses worldwide in a wide range of clinical conditions including angina, hypertension, rate control in atrial fibrillation/flutter, Marfan syndrome with an aortic aneurysm, migraine prophylaxis, thyrotoxicosis, anxiety, and essential tremor. 

Interestingly, in clinical practice atenolol is prescribed more for off-label uses than approved indications. 

#pharmacology


References:

1. Lin HW, Phan K, Lin SJ. Trends in off-label beta-blocker use: a secondary data analysis. Clin Ther. 2006 Oct;28(10):1736-46; discussion 1710-1. doi: 10.1016/j.clinthera.2006.10.015. PMID: 17157130.

2. Rehman B, Sanchez DP, Shah S. Atenolol. [Updated 2020 Oct 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539844/

Friday, April 2, 2021

Lyme carditis

 Q: Which finding on EKG is the best predictor of impending AtrioVentricular (AV) block in patients with Lyme carditis? 

Answer: PR interval greater than 300 milliseconds (ms) 

It takes about one to two months after infection for disseminated Lyme disease to show cardiac effects. Other systemic effects may occur at the same time including neurological symptoms. Once the heart gets involved patient may complain of palpitations and shows signs of conduction abnormalities, myocarditis, pericarditis, and CHF. Impending AV conduction abnormality sets off quickly and can be life-threatening. First-degree AV block quickly progresses to second or complete AV block. 

A PR interval greater than 300 milliseconds is a good predictor of impending AV block. Fortunately, it is reversible with treatment in few weeks. The drug of choice is IV ceftriaxone, which should be continued till the PR interval drops below 300 ms. Oral antibiotic maintained with doxycycline is required for few weeks.

#cardiology
#rheumatology


References:

1. Steere AC, Batsford WP, Weinberg M, et al. Lyme carditis: cardiac abnormalities of Lyme disease. Ann Intern Med 1980; 93:8.

2. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The Clinical Assessment, Treatment, and Prevention of Lyme disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006; 43:1089.

Thursday, April 1, 2021

cupola sign

 Q; What is  cupola sign?

Answer: Cupola sign is visible on the chest or abdominal x-ray and signifies the presence of pneumoperitoneum. "Cupola" is a Latin word and means "little cup". 

In a supine patient with pneumoperitoneum when non-dependent air rises up it can be seen as a lucency under the central area of the diaphragm. This lucency makes the lower thoracic vertebral bodies more prominent. This lucency appears as a cup with a well-defined upper border, Lower border of the cup remains unremarkable.



#radiology
#surgical-critical-care

Reference:

1. Fleming J, Honour H, Pevsner N. The Penguin Dictionary of Architecture: Fourth Edition. Penguin Books. ISBN:0140512411

2. Mindelzun RE, McCort JJ. The cupola sign of pneumoperitoneum in the supine patient. Gastrointest Radiol. 1986;11(3):283-5. doi: 10.1007/BF02035091. PMID: 3743953.