Rasburicase and the uric acid measurement

 Q; 42 years old male is transferred to ICU after he developed Tumor Lysis Syndrome (TLS) due to ongoing chemotherapy. Rasburicase is started. The uric acid will be? (select one) 

A) falsely high 

 B) falsely low 

Answer: B 

After the initiation of the Rasburicase, uric acid cannot be followed reliably to evaluate the response. Rasburicase can spuriously lower the uric acid. Rasburicase causes the enzymatic degradation of uric acid at room temperature in the collected sample. 

Ideally, specific orders should be written to collect the blood sample in a pre-chilled tube. Moreover sample should be placed on ice immediately. Rasburicase induced enzymatic degradation occurs over few hours, so the sample should be run STAT within 3-4 hours. Said that even this precaution may not help to have a reliable value (reference #2).

#oncology

#pharmacology

References:

1. Prescribing information for rasburicase available online at http://products.sanofi-aventis.us/elitek/elitek.html (Accessed on September 03, 2021). 

2. Depreter B, Stove V, Delanghe J. Sampling on ice will not yield reliable uric acid monitoring in rasburicase-treated patients. Clin Biochem. 2016 Dec;49(18):1390-1395. doi: 10.1016/j.clinbiochem.2016.04.011. Epub 2016 Apr 27. PMID: 27129796. 

3. Howard SC, Jones DP, Pui CH. The tumor lysis syndrome [published correction appears in N Engl J Med. 2018 Sep 13;379(11):1094]. N Engl J Med. 2011;364(19):1844-1854. doi:10.1056/NEJMra0904569

PAL

 Q: 52 years old Japanese male is admitted to ICU with fever, and community-acquired pneumonia. Follow-up workup led to the diagnosis of pyothorax-associated lymphoma (PAL). This is the long-standing complication of? (select one) 

A) Tuberculosis

B) Sarcoidosis

C) Smoking

D) Asbestosis

E) Cystic Fibrosis

Answer: A

PAL is a non-Hodgkin's lymphoma of B-cell phenotype. It evolves in the pleural cavity. So far all of these patients have a history of at least more than 20 years of pyothorax. It is mostly reported in patients who had treatment of artificial pneumothorax for pulmonary tuberculosis or tuberculous pleuritis. 

PAL has no association with immunosuppression. Although it is human herpesvirus type 8 (HHV-8) negative, more than two-thirds of these patients are Epstein-Barr virus (EBV)-positive. 5-year survival is around 20 percent. Most of these patients are Japanese males.

#pulmonary

#oncology

#ID

References:

1. Nakatsuka S, Yao M, Hoshida Y, Yamamoto S, Iuchi K, Aozasa K. Pyothorax-associated lymphoma: a review of 106 cases. J Clin Oncol. 2002 Oct 15;20(20):4255-60. doi: 10.1200/JCO.2002.09.021. PMID: 12377970. 

2. Aozasa K, Takakuwa T, Nakatsuka S. Pyothorax-associated lymphoma: a lymphoma developing in chronic inflammation. Adv Anat Pathol. 2005 Nov;12(6):324-31. doi: 10.1097/01.pap.0000194627.50878.02. PMID: 16330929.

COPD - life-threatening

 Q: 58 years old male with COPD exacerbation is admitted to ICU with respiratory rate of more than 30 breaths per minute. His oxygen saturation is 88% on a 35% Venturi mask (VM). ABG showed PCO2 of 58 mmHg. Which of the following will make it a life-threatening respiratory failure? (select one) 

A) use of accessory muscles 

B) acute mental status change

Answer: B 

As per Global Initiative for Chronic Obstructive Lung Disease (GOLD), COPD patients who require hospitalization are classified into three categories

• No respiratory failure 
• Acute nonlife-threatening respiratory failure
• Acute life-threatening respiratory failure

Contrary to popular belief, the use of accessory muscles of respiration is common and can be supported with non-invasive or invasive mechanical ventilation. Acute change in mental status, high oxygen requirement, severe hypercarbia or pH less than 7.25 makes it life-threatening.

#pulmonary

Reference:

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease: 2020 Report. http://www.goldcopd.org (Accessed on August 29, 2021).

Acetaminophen and ASA organ damage

 Q: Combined ingestion of aspirin and acetaminophen tends to cause more? (select one) 

A) Hepatic failure 

B) Renal failure 

Answer: B 

In intentional drug overdoses, it is common to ingest two or more drugs together, particularly easily accessible aspirin and acetaminophen. Acetaminophen after oxidative metabolism becomes reactive quinoneimine and gets conjugated to glutathione. On the other hand, aspirin gets converted to salicylate, which gets highly concentrated in the cortex and papillae of the kidney, where it depletes glutathione. Without glutathione depleted, the reactive quinoneimine of acetaminophen produces lipid peroxides causing necrosis and calcification of the papillae. 

Also, aspirin suppresses prostaglandin production resulting in decreased kidney blood flow and so ischemia potentiating the above mechanism.

#toxicology

References:

1. Duggin GG. Combination analgesic-induced kidney disease: the Australian experience. Am J Kidney Dis 1996; 28:S39. 

2. De Broe ME, Elseviers MM. Over-the-counter analgesic use. J Am Soc Nephrol 2009; 20:2098.

HCV in liver transplant

 Q: Patients with Hepatitis C (HCV) viremia who goes for a liver transplant, the reinfection is almost always with the same strain of the virus as prior to the transplant?

A) True

B) False

Answer: A

The major decision in patients with HCV who goes for liver transplant is to establish the timing for the HCV treatment. It can be either before or after the transplant. It is individualized by the transplant team. Various factors come into consideration such as the Child-Pugh class for cirrhosis, and likelihood of meaningful clinical as well as viremic response before transplant. The biggest caveat in treating HCV prior to transplant is the improvement in Model for End-Stage Liver Disease (MELD) score without any clinical improvement. This may harm the patients by increasing their wait time. 

Treatment of HCV after transplant is possible due to safe and effective HCV therapy with direct-acting antivirals (DAAs). The reinfection of donor's liver is almost always with the same strain of the virus as prior to the transplant.

#transplantation

#hepatology

References: 

1. Wright TL, Donegan E, Hsu HH, et al. Recurrent and acquired hepatitis C viral infection in liver transplant recipients. Gastroenterology 1992; 103:317. 

2. Cholankeril G, Joseph-Talreja M, Perumpail BJ, et al. Timing of Hepatitis C Virus Treatment in Liver Transplant Candidates in the Era of Direct-acting Antiviral Agents. J Clin Transl Hepatol. 2017;5(4):363-367. doi:10.14218/JCTH.2017.00007 

3. Chhatwal J, Samur S, Kues B, Ayer T, Roberts MS, Kanwal F, Hur C, Donnell DM, Chung RT. Optimal timing of hepatitis C treatment for patients on the liver transplant waiting list. Hepatology. 2017 Mar;65(3):777-788. doi: 10.1002/hep.28926. Epub 2017 Jan 6. PMID: 27906468; PMCID: PMC5319880.

Botulism

 Q: Botulism causes? (select one)

A) symmetric ascending weakness 

 B) symmetric descending weakness

Answer: B

The knowledge of the nature of paralysis in botulism is of clinical significance as patients exposed to botulism may be alert, have no fever but may have an acute onset of bilateral cranial neuropathies with symmetric descending weakness. Administration of antitoxin early in the course is of paramount importance. Human-derived botulism immune globulin (called BIG-IV or BabyBIG) is available but is off-label for adults. 

Moreover, intubation may be needed if vital capacity drops below 30 percent of the predicted.

#toxicology

References:

1. Chaudhry R. Botulism: a diagnostic challenge. Indian J Med Res. 2011;134(1):10-12. 

2. Cherington M. Clinical spectrum of botulism. Muscle Nerve. 1998 Jun;21(6):701-10. doi: 10.1002/(sici)1097-4598(199806)21:6<701::aid-mus1 style="color: #0c343d;">3.0.co;2-b. PMID: 9585323.

<701::aid-mus1 style="color: #0c343d;">3. Sobel J. Botulism. Clin Infect Dis. 2005 Oct 15;41(8):1167-73. doi: 10.1086/444507. Epub 2005 Aug 29. PMID: 16163636. 

<701::aid-mus1 style="color: #0c343d;">4. Chalk CH, Benstead TJ, Pound JD, Keezer MR. Medical treatment for botulism. Cochrane Database Syst Rev. 2019 Apr 17;4(4):CD008123. doi: 10.1002/14651858.CD008123.pub4. PMID: 30993666; PMCID: PMC6468196.

Anton Syndrome

 Q: What is Anton Syndrome?

Answer: 

The full nomenclature is Anton-Babinski syndrome. It occurs in the setting of cortical blindness. Patient denies vision loss (visual anosognosia). To compensate the denial, it is associated with confabulation. 

It can occur under various conditions like stroke, preeclampsia, head trauma, hypertensive encephalopathy or posterior reversible encephalopathy syndrome (PRES), autoimmune diseases involving CNS, Multiple sclerosis, fat embolism, and others.

#neurology

References:

1. Chaudhry FB, Raza S, Ahmad U. Anton's syndrome: a rare and unusual form of blindness. BMJ Case Rep. 2019 Dec 3;12(12):e228103. doi: 10.1136/bcr-2018-228103. PMID: 31801772; PMCID: PMC7001702.

2. Maddula M, Lutton S, Keegan B. Anton's syndrome due to cerebrovascular disease: a case report. J Med Case Rep. 2009;3:9028. Published 2009 Sep 9. doi:10.1186/1752-1947-0003-0000009028

CIRCI

 Q: The reason behind adrenal insufficiency in critical illness is? (select one) 

A) Subnormal corticosteroid production 

B) Increased cellular steroid utilization 

Answer: A 

During critical illnesses such as septic shock, the reason behind adrenal insufficiency is subnormal corticosteroid production. The hypothalamic-pituitary-adrenal axis stays intact. This is referred to as functional or relative adrenal insufficiency. Another designated term is "critical illness-related corticosteroid insufficiency (CIRCI)." The administration of steroids during pressor-resistant shock despite adequate fluid resuscitation is to balance the altered hypothalamic-pituitary-adrenal (HPA) axis. 

Despite the intact structure of the HPA axis, there are various reasons which lead to adrenal insufficiency. This includes HPA activation which actually increases the circulating cortisol, HPA impairment which causes adrenocortical hyporesponsiveness, and glucocorticoid resistance. 

Unfortunately, clinicians so far failed to reach any consensus definition of CIRCI, and management mostly depends on clinician's judgment and few guidelines.

#hemodynamics

References:

1. Boonen E, Vervenne H, Meersseman P, et al. Reduced cortisol metabolism during critical illness. N Engl J Med 2013; 368:1477. Malerba G, Romano-Girard F, Cravoisy A, et al. Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med 2005; 31:388. 

2. Cohen J, Pretorius CJ, Ungerer JP, et al. Glucocorticoid Sensitivity Is Highly Variable in Critically Ill Patients With Septic Shock and Is Associated With Disease Severity. Crit Care Med 2016; 44:1034. 

3. Burry LD, Wax RS. Role of corticosteroids in septic shock. Ann Pharmacother 2004; 38:464.

4. Annane D, Pastores SM, Rochwerg B, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Intensive Care Med 2017; 43:1751.

Gender in CHA2DS2-VASc score

 Q: In CHA2DS2-VASc score - what is the point allocation for gender? (select one)

A) Male=0, Female=1

B) Male=1, Female=0

Answer: A

CHA2DS2-VASc is a risk stratification score for estimation of stroke risk for nonvalvular atrial fibrillation (AF) in adults. Contrary to popular belief, females have a higher risk of strokes from nonvalvular AF. Said that it needs to acknowledge that not all experts believe in this discrepancy. This sex category (Sc) in CHA2DS2-VASc came from a strong retrospective cohort study of about 100,000 patients (Swedish registry) with AF which found that the risk of ischemic stroke in women was 6.2 percent vs. 4.2 percent per year in males. 

 C = congestive heart failure 

H = Hypertension

Ag e= Age > 75 years (2 points) 

D = Diabetes mellitus

S = Stroke or TIA or thromboembolism - prior 

V = Vascular disease 

Age = 65 to 74 years 

Sc = Sex category 

#cardiology

#neurology

References:

1. Friberg L, Benson L, Rosenqvist M, Lip GY. Assessment of female sex as a risk factor in atrial fibrillation in Sweden: nationwide retrospective cohort study. BMJ 2012; 344:e3522. 

2. Wagstaff AJ, Overvad TF, Lip GY, Lane DA. Is female sex a risk factor for stroke and thromboembolism in patients with atrial fibrillation? A systematic review and meta-analysis. QJM 2014; 107:955.

Khorana score

 Q: According to Khorana score which organ cancer has the highest risk of venous thromboembolism (VTE)? 

A) Stomach

B) Lung

C) Lymphoma

D) Gynecologic tumors 

E) Testicular 

Answer: A 

Khorana score was developed by Dr. Alok A. Khorana at the Cleveland Clinic and was first published in 2008. It estimates the risk of VTE in cancer patients. It is a validated score and has been re-tested with subsequent trials. It takes into account five factors to determine the risk of VTE 

• Site of the primary tumor 
• Pre-chemotherapy platelet count 
• Hemoglobin level 
• Pre-chemotherapy WBC count 
• BMI 

In Khorana score stomach and pancreas cancers were found to have the highest risk of VTE. Said that patients with brain tumors and myeloma were excluded from the trial published in 2008. 

Khorana score is available via various search engines.  Later on, CASSINI and AVERT trials looked into thromboprophylaxis in cancer patients.  

#oncology

#hematology

References:

1. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111:4902. 

2. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood 2010; 116:5377. 

3. Mandala M, Clerici M, Corradino I, et al. Incidence, risk factors and clinical implications of venous thromboembolism in cancer patients treated within the context of phase I studies: the 'SENDO experience'. Ann Oncol 2012; 23:1416.

4. Langhorne P, Wu O, Rodgers H, Ashburn A, Bernhardt J. A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial. Health Technol Assess. 2017 Sep;21(54):1-120. doi: 10.3310/hta21540. PMID: 28967376; PMCID: PMC5641820.

5. Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T, Streiff MB, Garcia DA, Liebman HA, Belani CP, O'Reilly EM, Patel JN, Yimer HA, Wildgoose P, Burton P, Vijapurkar U, Kaul S, Eikelboom J, McBane R, Bauer KA, Kuderer NM, Lyman GH; CASSINI Investigators. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer. N Engl J Med. 2019 Feb 21;380(8):720-728. doi: 10.1056/NEJMoa1814630. PMID: 30786186.

PAC complications reduction

Q: Most of the trauma while inserting a Pulmonary Artery Catheter (PAC) is due to inflation of the balloon during the catheter advancement?

A) True

B) False

Answer: B

Keeping the balloon at the tip of PAC (Swan-Ganz catheter) inflated while advancing the catheter minimizes the complications. Most of the complications during PAC insertion occur due to the direct exposure of the tip to the cardiac tissues. These include arrhythmias, catheter misplacement, perforation, rupture of the heart valve, and/or rupture of the pulmonary artery.  Once inflated, the balloon covers most of the tip and protects it from causing trauma. 

Similarly, keeping the balloon deflated during retrieval (backing off) is advisable.

#procedures

Reference:

1. Narumiya C, Isobe F. [Insertion procedure of the Swan-Ganz catheter]. Kyobu Geka. 2010 Jul;63(8 Suppl):607-11. Japanese. PMID: 20715426. 

2. Bossert T, Gummert JF, Bittner HB, Barten M, Walther T, Falk V, Mohr FW. Swan-Ganz catheter-induced severe complications in cardiac surgery: right ventricular perforation, knotting, and rupture of a pulmonary artery. J Card Surg. 2006 May-Jun;21(3):292-5. doi: 10.1111/j.1540-8191.2006.00235.x. PMID: 16684066.

feeding (gastric vs intestinal)

A note on Pros and Cons of gastric feeding in ICU

It should be understood that gastric feeding is more physiologic. It buffers gastric acid better. The gastropancreatic reflexes and gastrin release are more balanced. It enhances the pancreatic responses prior to food reaching the upper small bowel. In long term, it is easier to place and convenient to use. Moreover, the stomach can relatively tolerate a larger volume and higher osmotic load. 

Post-pyloric feeding should be utilized in situations where there is a chance of delayed gastric emptying, severe gastroesophageal reflux disease (GERD) and/or esophagitis causing nausea, vomiting, or aspiration pneumonia. Paralytic agents affect gastric motility more and post-pyloric feeding may be required if gastric intolerance may become an issue. 

#GI

References:

1. Tamion F, Hamelin K, Duflo A, Girault C, Richard JC, Bonmarchand G. Gastric emptying in mechanically ventilated critically ill patients: effect of neuromuscular blocking agent. Intensive Care Med. 2003 Oct;29(10):1717-22. doi: 10.1007/s00134-003-1898-5. Epub 2003 Jul 30. PMID: 12897996. 

2. Weledji EP. Perspectives on paralytic ileus. Acute Med Surg. 2020;7(1):e573. Published 2020 Oct 4. doi:10.1002/ams2.573 

3. Murray MJ, DeBlock H, Erstad B, Gray A, Jacobi J, Jordan C, McGee W, McManus C, Meade M, Nix S, Patterson A, Sands MK, Pino R, Tescher A, Arbour R, Rochwerg B, Murray CF, Mehta S. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med. 2016 Nov;44(11):2079-2103. doi: 10.1097/CCM.0000000000002027. PMID: 27755068.

Danger Space

 Q: What is "Danger Space" in the anatomy of the head and neck? 

Answer: Going from vertebra to pharyngeal area (posterior to anterior), there are three spaces:

1. Prevertebral space

2. Danger space

3. Retropharnygeal space

Danger Space extends from the base of the skull downwards freely through the entire posterior mediastinum to the level of the diaphragm. Vertebrally it corresponds with T11-T12. 

Clinical significance: Potentially, it provides a very functional route for the contiguous spread between the neck and the chest.

#ID

#anatomy

References: 

1. Reynolds SC, Chow AW (2009). "Severe soft tissue infections of the head and neck: a primer for critical care physicians". Lung. 187 (5): 271–9. doi:10.1007/s00408-009-9153-7. PMID 19653038. 

2. Mark, R., Song, S., & Mark, P. (2018). Taking heed of the 'danger space': acute descending necrotising mediastinitis secondary to primary odontogenic infection. BMJ case reports, 2018, bcr2018225019. https://doi.org/10.1136/bcr-2018-225019 

3. Grodinsky M, Holyoke EA. The fasciae and fascial spaces of the head, neck and adjacent regions. Am J Anat 1938;63:367-408.

CDS

 Q: 64 years old male is admitted to ICU with sudden onset of severe neck pain, stiffness, and fever. CT scan of the neck reads possible "Crowned Dens Syndrome." What is Crowned Dens Syndrome? 

Answer: Crowned dens syndrome is a rheumatological disorder that mimics an acute infectious process. It is due to the deposition of hydroxyapatite crystals, or calcium pyrophosphate in the periodontoid tissues, and gives an appearance of the dens on imagings. CT scan of the neck usually shows periodontoid calcification of C1-C2, with an appearance of a crown or halo surrounding the odontoid process. 

Symptoms of CDS are fever associated with acute severe shoulder girdle and neck stiffness. Diagnosis is via elevation of acute phase reactants. Treatment is nonsteroidal anti-inflammatory drugs (NSAIDs). Colchicine works well too.

#rheumatology

References:

1. Aouba A, Vuillemin-Bodaghi V, Mutschler C, De Bandt M. Crowned dens syndrome misdiagnosed as polymyalgia rheumatica, giant cell arteritis, meningitis or spondylitis: an analysis of eight cases. Rheumatology (Oxford) 2004; 43:1508. 

 2.Uh M, Dewar C, Spouge D, Blocka K. Crowned dens syndrome: a rare cause of acute neck pain. Clin Rheumatol 2013; 32:711.

AP-CML

 Q: Accelerated phase (AP) of Chronic Myeloid Leukemia (CML) should be considered a part of the blast phase (BP) CML? 

A) Yes 

B) No 

Answer: B 

Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with Philadelphia chromosome. The objective of this question is to highlight the fact that chronic phase (CP) CML, accelerated phase (AP) CML, and blast phase (BP) CML are three distinct scenarios.

All three entities are differentiated on the basis of myeloblast count, percentage of basophils, additional chromosomal abnormalities, and clinical features. Further, AP-CML can be a de novo or a transformation of CP CML - where prognosis and treatments may be different.  Like, CP-CML responds well to treatment with a BCR-ABL1 tyrosine kinase inhibitor (TKI). 

There are three usually followed criteria for AP-CML: 1) World Health Organization (WHO), 2) European LeukemiaNet (ELN) and 3) MD Anderson Cancer Center (MDACC). 

#oncology

References:

1. Mukherjee S, Kalaycio M. Accelerated Phase CML: Outcomes in Newly Diagnosed vs. Progression From Chronic Phase. Curr Hematol Malig Rep. 2016 Apr;11(2):86-93. doi: 10.1007/s11899-016-0304-7. PMID: 26932346. 

2. Aladağ E, Haznedaroğlu İC. Current perspectives for the treatment of chronic myeloid leukemia. Turk J Med Sci. 2019 Feb 11;49(1):1-10. doi: 10.3906/sag-1810-81. PMID: 30761815; PMCID: PMC7350850.

HD in Carbamazepine overdose

Q:  What is the best way to assess the effectiveness of hemodialysis in carbamazepine toxicity? 

 Answer:  Unfortunately, hemodialysis (HD) is not very effective in carbamazepine toxicity as it is highly protein-bound. Although, as a last resort it can be employed but only high-flux hemodialysis may work or the use of albumin-containing dialysate. Continuous venovenous hemodialysis (CVVHD) can be employed in hemodynamically unstable patients but results may not be as desirable. 

Another option is to use charcoal hemoperfusion but it is not easily available at most institutions and is not as safe as regular HD. It may cause thrombocytopenia, coagulopathy, hypothermia, hypocalcemia, hypophosphatemia, and hypoglycemia. The data on plasmapheresis/plasma exchange is also very limited. 

If HD is employed to remove carbamazepine, the best way to know if it's working is to measure the concentration of carbamazepine in the dialysate.

Administration of soda bicarbonate with QRS measurement continues to be the mainstay of treatment in carbamazepine overdose (reference #2).

#toxicology

References:

1. Schuerer DJ, Brophy PD, Maxvold NJ, et al. High-efficiency dialysis for carbamazepine overdose. J Toxicol Clin Toxicol 2000; 38:321. 

2. Bradberry SM, Thanacoody HK, Watt BE, et al. Management of the cardiovascular complications of tricyclic antidepressant poisoning : role of sodium bicarbonate. Toxicol Rev 2005; 24:195.

3. Bek K, Koçak S, Ozkaya O, et al. Carbamazepine poisoning managed with haemodialysis and haemoperfusion in three adolescents. Nephrology (Carlton) 2007; 12:33.

Hyperfiltration

 Q: Glomerular hyperfiltration is a protective sign in diabetic patients? 

A) Yes 

B) No 

 Answer: B

Early in the course in some diabetic patients the Glomerular Filtration Rate (GFR) becomes higher than normal. This is called glomerular hyperfiltration, and is defined as "GFR 20 percent or more above that in age-matched, healthy controls without diabetes." Unfortunately, it is not a good sign. Hyperfiltration predicts a higher risk of greater albuminuria and so the progression of Diabetic Kidney Disease (DKD). 

These patients benefit from the nephroprotective effect of the renin-angiotensin system (RAS) and sodium-glucose co-transporter 2 (SGLT2) inhibitors.

#nephrology

References:

1. Vora JP, Dolben J, Dean JD, et al. Renal hemodynamics in newly presenting non-insulin dependent diabetes mellitus. Kidney Int 1992; 41:829. 

2. Tonneijck L, Muskiet MH, Smits MM, et al. Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment. J Am Soc Nephrol 2017; 28:1023. 

3. Magee GM, Bilous RW, Cardwell CR, et al. Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis. Diabetologia 2009; 52:691. 

4. Ruggenenti P, Porrini EL, Gaspari F, et al. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care 2012; 35:2061.

SSRIs and QTc

 Q: 68 years old male collapsed at home, where EMS found him in polymorphic ventricular tachycardia (torsade de pointes). He was revived and is now in ICU. His wife informed that recently the dose of one of his anti-depressants (SSRI) was increased. Which of the following Selective Serotonin Reuptake Inhibitors (SSRIs) is most prone to cause prolong QTc interval?

A) Citalopram 

B) Escitalopram 

C) Fluoxetine 

D) Paroxetine 

E) Sertraline

Answer: A

All of the SSRIs can cause prolonged QTc. It is a dose-dependent effect. Usually, most patients have no clinical impact, but Citalopram (Celexa) may cause a life-threatening arrhythmia, usually torsade de pointes. This effect is likely at the dose of 60 mg per day. It is recommended not to exceed the dose above 40 mg per day. If required serum concentrations of citalopram can be followed. 

Moreover, when a higher dose is needed, close monitoring of electrolytes particularly potassium and magnesium should be done. Also, care should be taken to avoid drug-drug interactions with polypharmacy.

Celexa is one of the most common SSRIs prescribed in the USA.

#psychiatry

#pharmacology

References:

1. FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses http://www.fda.gov/Drugs/DrugSafety/ucm297391.htm (Accessed on August 11, 2021).

2. Girardin FR, Gex-Fabry M, Berney P, et al. Drug-induced long QT in adult psychiatric inpatients: the 5-year cross-sectional ECG Screening Outcome in Psychiatry study. Am J Psychiatry 2013; 170:1468. 

3. Castro VM, Clements CC, Murphy SN, et al. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 2013; 346:f288. 

4. Bird ST, Crentsil V, Temple R, et al. Cardiac safety concerns remain for citalopram at dosages above 40 mg/day. Am J Psychiatry 2014; 171:17.

IBD-PSC

 Q: Primary Sclerosing Cholangitis (PSC) is usually associated with? (select one)

A) Crohn's disease 

B) Ulcerative colitis

Answer: B

Almost 90 percent of patients with PSC have ulcerative colitis (UC), though vice versa is not necessary. This is due to the fact that patients who have both PSC and inflammatory bowel disease (IBD) carry a different phenotype than patients who have only IBD. All patients with IBD who have abnormal liver enzymes particularly serum alkaline phosphatase should undergo workup for PSC. 

Clinically distinct features of patients who have both UC and PSC is pancolitis with active histologic activity despite the minimal endoscopic activity.

#GI

References:

1. Tung BY, Brentnall T, Kowdley KV, et al. Diagnosis and prevalence of ulcerative colitis in patients with sclerosing cholangitis (abstract). Hepatology 1996; 24:169A. 

2. Loftus EV Jr, Harewood GC, Loftus CG, et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut 2005; 54:91. 

3. Boonstra K, van Erpecum KJ, van Nieuwkerk KM, et al. Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis 2012; 18:2270. 

4. Jørgensen KK, Grzyb K, Lundin KE, et al. Inflammatory bowel disease in patients with primary sclerosing cholangitis: clinical characterization in liver transplanted and nontransplanted patients. Inflamm Bowel Dis 2012; 18:536.

Anbx in Nontyphoidal Salmonella gastroenteritis

 Q: All of the following are the indications for antimicrobial therapy in nontyphoidal Salmonella gastroenteritis EXCEPT? 

A) Severe diarrhea 

B) High or persistent fever 

C) Need for hospitalization 

D) Blood-stained diarrhea 

Answer: D

Antimicrobial therapy is usually not recommended for nontyphoidal salmonella gastroenteritis. This increases the risk for asymptomatic Salmonella carriage without any benefit. Antimicrobials should be used only if diarrhea is severe (> 10 stools per day), fever is either high or persistent, or there is a need for hospitalization. 

The blood in the stool is not an indication for antimicrobial in nontyphoidal salmonella gastroenteritis. Moreover, salmonella gastroenteritis is rarely marked by overt blood in the stool. It should raise the suspicion of Shigella or enterohemorrhagic E. coli.

#ID

#GI

References:

1. Onwuezobe IA, Oshun PO, Odigwe CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev 2012; 11:CD001167. 

2. Hung YT, Lay CJ, Wang CL, Koo M. Characteristics of nontyphoidal Salmonella gastroenteritis in Taiwanese children: A 9-year period retrospective medical record review. J Infect Public Health. 2017 Sep-Oct;10(5):518-521. doi: 10.1016/j.jiph.2016.09.018. Epub 2017 Feb 13. PMID: 28209468.

Digi-bind

 Q: Digoxin-specific antibody (Fab) fragments can be given as an IV push in a 'code' situation?

A) Yes

B) No

Answer: A

Ideally, Fab fragments should be given as an intravenous (IV) piggy bag over a half-hour period, but during cardiac arrest (code) or impending cardiac arrest, it can be given as a slow IV push. 

Another objective of this question is to emphasize the need for caution in giving Fab fragments to patients who are chronically on digoxin. In such patients, digoxin induced arrhythmia - such as AV nodal block - without hemodynamic compromise (means only EKG changes), should be treated with half of the calculated dose. Full dose Fab fragments in these patients may unmask the heart failure and may put the patient in cardiogenic shock or atrial fibrillation with the rapid ventricular response (A.fib. with RVR).

#cardiology

#pharmacology

References:

1. Bateman DN. Digoxin-specific antibody fragments: how much and when? Toxicol Rev. 2004;23(3):135-43. doi: 10.2165/00139709-200423030-00001. PMID: 15862081.

2. Chan BS, Buckley NA. Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Clin Toxicol (Phila). 2014 Sep-Oct;52(8):824-36. doi: 10.3109/15563650.2014.943907. Epub 2014 Aug 4. PMID: 25089630.

ESR and APR

 Q: 'Erythrocyte sedimentation rate' (ESR) is a/an ____________ acute phase reactant? (select one)

A) direct

B) indirect

Answer: B

Acute phase reactants (APR) are the proteins whose serum concentrations increase (positive) or decrease (negative) by at least 25 percent during inflammatory states such as infection, trauma, tumor, infarction, or autoimmune diseases. 

'Erythrocyte sedimentation rate' (ESR) is actually not a protein, rather it represents the increased viscosity of the serum due to these acute-phase proteins, mostly fibrinogen. That's why it is called indirect APR.

#inflammation

Reference:

Bedell SE, Bush BT. Erythrocyte sedimentation rate. From folklore to facts. Am J Med 1985; 78:1001.

Quinsy

 Q: 26 years old male is admitted to ICU for airway vigilance and signs of sepsis due to peritonsillar abscess. On physical exam, the uvula is expected to deviate towards? (select one) 

A) the affected side 

B) the unaffected side

Answer: B

Peritonsillar abscess is popularly known as quinsy. This is a suppurative extension of acute tonsillitis into the peritonsillar space. It is common in young adults. It is usually an abscess formation near the superior pole of the tonsil. Signs and symptoms consist of fever, odynophagia, sore throat which tends to be unilateral, otalgia, muffled voice (hot potato voice), trismus, unilateral deviation of the uvula towards the unaffected side, and soft palate edema.  

It requires quick recognization and treatment with drainage and/or antibiotics to avoid airway compromise. In severe edema, steroids can be considered.

#ID

#ENT

#surgical-critical-care

References:

1. Galioto NJ. Peritonsillar Abscess. Am Fam Physician. 2017 Apr 15;95(8):501-506. PMID: 28409615.

2. Steyer TE. Peritonsillar abscess: diagnosis and treatment. Am Fam Physician. 2002 Jan 1;65(1):93-6. Erratum in: Am Fam Physician 2002 Jul 1;66(1):30. PMID: 11804446.

shocks

 Q; Patients with severe acute myocardial infarction (MI) can have? (select one)

A) cardiogenic shock 

B) obstructive shock 

C) hemorrhagic shock 

D) all of the above

Answer: D

The objective of the above question is to highlight the fact that most shock situations are rarely a pure single entity. They may start as a single form of shock such as distributive, hypovolemic, hemorrhagic, or mechanical but soon culminate into a combined form of shock. 

One of the examples is severe acute MI which may start as a pure cardiogenic shock but with a ruptured left ventricular wall, may become an obstructive shock because of cardiac tamponade - or hemorrhagic shock with blood loss. Similarly, septic shock may start as a pure distributive shock bur after massive volume resuscitation, may culminate into mechanical shock due to abdominal compartment syndrome, and/or cardiogenic shock due to acute right heart failure.

#hemodynamics

References:

1. Standl T, Annecke T, Cascorbi I, Heller AR, Sabashnikov A, Teske W. The Nomenclature, Definition and Distinction of Types of Shock. Dtsch Arztebl Int. 2018;115(45):757-768. doi:10.3238/arztebl.2018.0757

2. Kislitsina ON, Rich JD, Wilcox JE, et al. Shock - Classification and Pathophysiological Principles of Therapeutics. Curr Cardiol Rev. 2019;15(2):102-113. doi:10.2174/1573403X15666181212125024

Applying lidocaine while inserting chest-tube

 Q: While anesthetizing the chest area to insert thoracostomy tube (chest tube) - think of a step missing from below as the anesthesia needle moves forward. 

1. Apply lidocaine to skin and subcutaneous (SC) tissues 

 2. Apply lidocaine to the periosteum of the rib above and the rib below 

3. Avoid the lower rib margin 

4. Apply lidocaine into the muscles of the intercostal space where the chest tube is planned 

5. Apply lidocaine to the area of the parietal pleura where the tube will enter the pleural space.

Answer: The objective of this question is to highlight an important step frequently missed by the operators while anesthetizing the area for the chest tube insertion.

After applying lidocaine to the skin and the SC tissues, and going forward, the anesthesia needle should be aspirated back to make sure that the needle is not in the intercoastal artery or vein. The damage to an intercoastal vessels can be fatal. In lean and thin patients this may need to be done as a first step.

#procedure

References:

1. Kwiatt M, Tarbox A, Seamon MJ, et al. Thoracostomy tubes: A comprehensive review of complications and related topics. Int J Crit Illn Inj Sci. 2014;4(2):143-155. doi:10.4103/2229-5151.134182

2. Durai R, Ng PC. How to insert a perfect chest drain. Acta Chir Belg. 2009 Oct;109(5):652-4. doi: 10.1080/00015458.2009.11680510. PMID: 19994817.

Florinef

 A note on Fludrocortisone 

Fludrocortisone is actually 9-alpha-fluorohydrocortisone. It is a synthetic mineralocorticoid. It increases renal sodium and water reabsorption leading to intravascular volume expansion. Fludrocortisone is frequently used in outpatient settings, particularly in End-Stage Renal Disease (ESRD) patients. If possible, it should be continued in ESRD patients in ICU if there is no major contraindication. Independently, it has low efficacy in acute situations. It takes about five to seven days to show clinical effect. The dose is anywhere from 0.05 mg to 0.2 mg per day. 

Said that Dr. Annane showed that the addition of Fludrocortisone with stress dose steroid may reduce 90-days mortality in septic shock (see reference #2) - though the level of evidence is weak. This may be due to the fact that Fludrocortisone by itself provides synergism to the pressor effect of sympathomimetic drugs/drips.  

Fludrocortisone has an interesting side effect of supine hypertension. It may also worsen edema and CHF. It has a tendency to cause hypokalemia, which may be beneficial in renal patients but should be a lookout in other patients.

#hemodynamics

References:

1. Chobanian AV, Volicer L, Tifft CP, et al. Mineralocorticoid-induced hypertension in patients with orthostatic hypotension. N Engl J Med 1979; 301:68. 

2. Annane D, et al. CRICS-TRIGGERSEP Network. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018 Mar 1;378(9):809-818. doi: 10.1056/NEJMoa1705716. PMID: 29490185. 

3. Veazie S, Peterson K, Ansari Y, et al. Fludrocortisone for orthostatic hypotension. Cochrane Database Syst Rev 2021; 5:CD012868.

Lasix-albumin drip

 Q: Albumin-furosemide infusion is usually more efficacious than furosemide (Lasix) infusion alone? 

A) True

B) False

Answer: B

Although this is a very common practice in ICUs to add albumin with furosemide, popularly known as Lasix-albumin drip, to increase the diuresis. This is done with the hope that as these patients usually have low albumin, and the addition of albumin will bring the extracellular fluid within the vascular space and keep furosemide within the vascular space, and so will increase efficacy of the diuresis and natriuresis. 

Unfortunately, this practice lacks any evidence. There is no extra net sodium loss. This has been demonstrated in both nephrotic syndrome and cirrhotic patients.

#nephrology

References:

1. Fliser D, Zurbrüggen I, Mutschler E, et al. Coadministration of albumin and furosemide in patients with the nephrotic syndrome. Kidney Int 1999; 55:629. 

2. Chalasani N, Gorski JC, Horlander JC Sr, et al. Effects of albumin/furosemide mixtures on responses to furosemide in hypoalbuminemic patients. J Am Soc Nephrol 2001; 12:1010.

Whirl sign

 Q: What is 'CT whirl sign' in 'closed-loop bowel obstruction'? 

Answer: As the name implies closed-loop bowel obstruction is a segment of the bowel with no proximal or distal outlet due to obstruction at two places. Although sounds simple, it is a surgical emergency, which requires early intervention, as necrosis due to ischemia and perforation can occur very quickly. Restoration of perfusion is urgently needed. Sometimes it needs full abdominal exploration. Another caveat is its difficult diagnosis via imaging. 

CT whirl sign: A closed-loop obstruction should be suspected if a C or U-shaped distended, fluid-filled bowel segment with prominent mesenteric vessels converging on a point of torsion or incarceration is seen. 

Other clues in imaging are the presence of a triangular bowel loop, the beak sign (gradual narrowing of the bowel), and the two collapsed bowel loops adjacent to the obstruction site.

#surgical-critical-care

References:

1. Mbengue, A., Ndiaye, A., Soko, T. O., Sahnoun, M., Fall, A., Diouf, C. T., Régent, D., & Diakhaté, I. C. (2015). Closed loop obstruction: pictorial essay. Diagnostic and interventional imaging, 96(2), 213–220. https://doi.org/10.1016/j.diii.2013.10.011 

2. Ho YC. "Venous cut-off sign" as an adjunct to the "whirl sign" in recognizing acute small bowel volvulus via CT scan. J Gastrointest Surg 2012; 16:2005. 

3. Elsayes, K. M., Menias, C. O., Smullen, T. L., & Platt, J. F. (2007). Closed-loop small-bowel obstruction: diagnostic patterns by multidetector computed tomography. Journal of computer assisted tomography, 31(5), 697–701. https://doi.org/10.1097/RCT.0b013e318031f516. 

4. Edwards, M. K., Kuppler, C. S., Croft, C. A., & Eason-Bates, H. M. (2018). Adhesive Closed-loop Small Bowel Obstruction. Clinical practice and cases in emergency medicine, 2(1), 31–34. https://doi.org/10.5811/cpcem.2017.10.35927

Vitamin K

 Q: Vitamin K can be administrated after diluting with orange juice?

A) Yes

B) No

Answer: A

Administration of Vitamin K (phytonadione) in ICU via intravenous (IV) infusion is common, but this should always be remembered that despite all precautions such as enough dilution and slow infusion fatal reaction may occur with IV infusion. Extra precaution should be taken if a patient is receiving vitamin K for the first time. Moreover, this can occur via the intramuscular (IM) route too where there is an extra risk of hematoma formation. The subcutaneous route is safe but carries the risk of erratic and unpredictable absorption. 

The objective of this question is to emphasize that the oral route is the best route for vitamin K unless an urgent reversal of coagulopathy is needed. It can also be administrated by diluting in beverages if a pill cannot be swallowed. 

Another mistake many clinicians do is by ordering an ala-carte dose of 10 mg even in non-urgent cases. A lower dose of 1 to 2.5 mg is usually sufficient. 10 mg should be given in extremely urgent cases of bleeding.

#pharmacology

#hematology

References:

1. Vanier MC and Ngo TT. Reversal of overanticoagulation with vitamin K1: A plea for oral administration. Can J Hosp Pharm. 2006;59:125-135. 

2. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2)(suppl):e44s-e88s. doi:10.1378/chest.11-2292

Scleroderma Renal Crisis

 Q: Which of the following is NOT a part of the classic scleroderma renal crisis (SRC)? (select one)? 

A) Abrupt malignant hypertension 

B) Acute oliguric renal failure 

C) Severe proteinuria 

D) Microangiopathic hemolysis anemia 

E) Thrombocytopenia 

 Answer: C 

SRC is one of the most dreaded complications of scleroderma Although some level of kidney involvement is a norm in scleroderma, it rarely progresses to chronic renal failure. SRC may occur in 10-15 percent of cases. What makes it scarier is that it usually occurs early in the course and can catch physicians as well as patients off guard. One clinical predictor is the patient with diffuse cutaneous Systemic Sclerosis (dcSSc). Patients with limited cutaneous systemic sclerosis (lcSSc) are less inclined to develop this. It has the following classic clinical characteristics:

• Abrupt onset of high/malignant hypertension. (some reports of normal blood pressure)
• Acute oliguric renal failure 
• Urinalysis with only mild proteinuria with few cells or casts 
• Microangiopathic hemolytic anemia 
• Thrombocytopenia 

The above pathologies lead to the possible symptoms of shortness of breath from pulmonary edema, headache, blurred vision, retinal microhemorrhages, hypertensive encephalopathy, and seizures. 

Please see reference #3 for recent updates on SRC's management.

#rheumatology

#nephrology

References:

1. Traub YM, Shapiro AP, Rodnan GP, et al. Hypertension and renal failure (scleroderma renal crisis) in progressive systemic sclerosis. Review of a 25-year experience with 68 cases. Medicine (Baltimore) 1983; 62:335. 

2. Shanmugam VK, Steen VD. Renal disease in scleroderma: an update on evaluation, risk stratification, pathogenesis and management. Curr Opin Rheumatol 2012; 24:669.

3. Nagaraja V. (2019). Management of scleroderma renal crisis. Current opinion in rheumatology, 31(3), 223–230. https://doi.org/10.1097/BOR.0000000000000604

Poxes

 Q: 42 years old male recently with a history of HIV is admitted to ICU with COVID-19. On examination, noticed to have large firm, dome-shaped papules on the genitals. ID service made the diagnosis of Molluscum contagiosum virus (MCV) (Poxvirus). Which areas of the body are typically spared providing clues to the diagnosis? (select one) 

 A) palms and soles 

B) axillae and popliteal fossae

Answer: A

Few risk factors for the Molluscum contagiosum virus in adults are sexual transmission, contact sports, inherited immunodeficiencies, and treatment with immunosuppressive drugs. It occurs as firm, dome-shaped papules. Pruritus may not be present. Characteristically, palms and soles are spared. 

In non-sexual transmissions usual areas of involvement are trunk, axillae, antecubital popliteal fossae, and crural folds. It may cause conjunctivitis by touching. Lesions in sexually transmitted MCV are present in the groin, genitals, proximal thighs, and lower abdomen. In HIV and immunocompromised patients, lesions are usually large and called giant molluscum and are widespread in the body due to underlying systemic disease. 

There are four genera of poxviruses 

• Orthopox causes smallpox (variola), vaccinia (Indian-subcontinent), cowpox, monkeypox (west and central africa), and rabbitpox viruses 
• Parapox causes orf, pseudocowpox, bovine papular stomatitis viruses 
• Yatapox causes tanapox and yaba monkey tumor viruses 
• Molluscipox causes molluscum contagiosum virus (MCV) 

Chickenpox is not a true pox virus and is caused by the herpes virus varicella-zoster.

#ID

References:

1. Zorec TM, Kutnjak D, Hošnjak L, et al. New Insights into the Evolutionary and Genomic Landscape of Molluscum Contagiosum Virus (MCV) based on Nine MCV1 and Six MCV2 Complete Genome Sequences. Viruses 2018; 10. 

2. Vora RV, Pilani AP, Kota RK. Extensive Giant Molluscum Contagiosum in a HIV Positive Patient. J Clin Diagn Res. 2015;9(11):WD01-WD2. doi:10.7860/JCDR/2015/15107.6797

DAPT and Diabetes

 Q: The effect of clopidogrel may be ___________ in diabetic patients?

A) decreased

B) increased

Answer: A

Physiologically, diabetic patients tend to have high platelet activation. This leads to relatively higher circulating immature platelets in their blood, and so the decreased function of anti-platelet drugs. The diabetic patients who present with coronary symptoms though should not be treated differently but their potential lack of response to Dual Anti-Platelet Therapy (DAPT) should be kept in mind. 

Diabetic patients who are compliant but less responsive to DAPT, may require a higher dose of Aspirin (ASA) and/or stronger platelet inhibitors like prasugrel or ticagrelor instead of clopidogrel.

#cardiology

#pharmacology

References:

1. Bouman HJ, van Werkum JW, Hackeng CM, et al. The importance of anticoagulant agents in measuring platelet aggregation in patients treated with clopidogrel and aspirin. J Thromb Haemost 2008; 6:1040. 

2. Duzenli MA, Ozdemir K, Aygul N, et al. Comparison of increased aspirin dose versus combined aspirin plus clopidogrel therapy in patients with diabetes mellitus and coronary heart disease and impaired antiplatelet response to low-dose aspirin. Am J Cardiol 2008; 102:396. 

3. Angiolillo DJ, Bernardo E, Zanoni M, et al. Impact of insulin receptor substrate-1 genotypes on platelet reactivity and cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 2011; 58:30. 

4. Grove EL, Hvas AM, Kristensen SD. Immature platelets in patients with acute coronary syndromes. Thromb Haemost 2009; 101:151. 

5. Michos ED, Ardehali R, Blumenthal RS, et al. Aspirin and clopidogrel resistance. Mayo Clin Proc 2006; 81:518. 

6. Gurbel PA, Bliden KP, Butler K, et al. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation 2010; 121:1188.