VA QI Morning Report – PICC?

This morning at the VA we did a mini M&M based on this case regarding the appropriateness of PICC lines in a patient with CKD/ESRD with diabetes and osteomyelitis.

PICCs should generally be avoided in patients with an eGFR <45 ml/min/1.73m2 or placed only after consultation with a nephrologist. The reason for this is PICC placement can harm future candidacy for AV fistula placement, the safest and most effective method of hemodialysis.

There are alternatives for patients needing long-term IV access that may preserve the central and peripheral vasculature in the event HD is needed. The MAGIC criteria have helped to delineate the most appropriate intravenous catheter for your patient. The original paper, published in 2015, can be found here. The authors have also developed an app, which can be found here.


Parkland Morning Report 7/18 – Lupus Cerebritis

At today’s morning report at Parkland R2 Corbin Eule presented a case of a 68 year-old female with 2 weeks of confusion and lower extremity motor and sensory neuropathy, on a background of chronic fatigue, malaise and unintentional weight loss.

Our case discussion was led by pulmonary/ critical care faculty Dr Carlos Girod. The initial differential was broad and included malignancy with paraneoplastic syndrome, connective tissue disorders, and infiltrative disorders such as amyloidosis and sarcoidosis. The patient’s admission labs were notable for pancytopenia and normal renal function and urine sediment. An autoimmune panel was revealing with ANA >1:2560, positive anti-dsDNA antibodies, and low complement levels. Subsequent studies included a bone marrow biopsy showing LE cells and peripheral nerve biopsy consistent with vasculitis.

The patient was diagnosed with systemic lupus erythematosus (SLE) and received a course of “pulse” dose methylprednisolone followed by initiation of mycophenolate and an oral prednisone taper, with which she clinically improved.

SLE Pearls:

–     SLE may present with a wide variety of neuropsychiatric manifestations, including cognitive dysfunction, encephalopathy, polyneuropathy, psychosis, mood disorders, and coma1.

–     Neuropathy associated with SLE is thought to be due to vasculopathy of the small arteries supplying nerves; given the systemic nature of the disease, multiple nerves can be affected at once2.

–     LE cells were first described in 1948 by hematologists Dr Malcolm Hargraves and Dr Robert Morton, who found cells in the bone marrow of patients with SLE that appeared to have had their nuclei phagocytosed by mature polymorphonuclear cells3.

Clinical Presentation:

–     SLE is diagnosed by likelihood (definite, probable or possible SLE) using clinical and immunologic criteria such as that described by the American College of Rheumatology (ACR)4 or the Systemic Lupus International Collaborating Clinics (SICC)5.

–     The presence of neurologic manifestations in the absence of other known causes is one of the clinical criteria described by both societies, as is the presence of blood cell dyscrasias (hemolytic anemia, thrombocytopenia, leuko- or lympho-penia), and serum autoantibodies (ANA, anti-dsDNA, anti-Sm or antiphospholipid antibodies) that were seen in this case.


–     Treatment of SLE depends on the severity of the flare, with systemic corticosteroids and immunosuppressants forming the mainstay of treatment.

–     Determining dosing intensity and duration of corticosteroid therapy for treatment of SLE is challenging. Whereas historically “pulse” steroids (methylprednisolone 0.5 to 1g/day for 3 days) were commonly regarded as the gold standard for severe SLE flares, more recent evidence suggests that lower doses may be equally efficacious, with reduction in infectious side effects6.


1. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis and rheumatism. 1999;42(4):599-608.

2. Florica B, Aghdassi E, Su J, Gladman DD, Urowitz MB, Fortin PR. Peripheral neuropathy in patients with systemic lupus erythematosus. Seminars in arthritis and rheumatism. 2011;41(2):203-211.

3. Hepburn AL. The LE cell. Rheumatology (Oxford). 2001;40(7):826-827.

4. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis and rheumatism. 1997;40(9):1725.

5. Petri M, Orbai AM, Alarcon GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis and rheumatism. 2012;64(8):2677-2686.

6. Badsha H, Edwards CJ. Intravenous pulses of methylprednisolone for systemic lupus erythematosus. Seminars in arthritis and rheumatism. 2003;32(6):370-377.

Joey Harrington Publishes!


R3 Dr. Josephine Harrington published her new review “Should Metformin Remain First-Line Therapy for Patients with Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease? An Alternative Approach” today in Current Diabetes Reports.


Dr. Harrington reviews the evidence for cardiovascular effects of antihyperglycemic agents, proposing the major aim of therapy of type 2 diabetes should be to reduce CV events and deaths. In the face of newly developed diabetes therapies with proven CV safety, is metformin the best option to improve CV outcomes?


Dr. Harrington publishes this review with former UTSW IM resident and current UTSW cardiology fellow Natalia de Albuquerque Rocha, UTSW cardiology fellow Kershaw Patel , Dr. Subodh Verma, and UTSW Cardiologist Dr. Darren McGuire. The review can be found here.

Cox’s Conference: Enteric Fever

In last week’s Ambulatory Cox’s Conference, Dr. Roger Fan presented a case of a young female who presented with fevers, rash, and headache. Our expert discussant, Dr. James Luby guided us through the differential diagnosis for the constellation of symptoms – fever, rash, and headache.

In a patient with an acute presentation of fever, rash, and headache the differential diagnosis is broad and includes infectious, autoimmune, and drug-related reactions etiologies. It is important to elicit a thorough history from the patient including travel history, exposures (insects, animals, sick contacts), medications, immunization history, and immune status of the host. The patient had history of recent travel to Nepal to visit family. Our differential diagnosis in this patient included common viral illnesses (EBV, CMV, and HIV), tick-born illnesses (Rocky Mountain spotted fever, Ehrlichiosis/anaplasmosis, and Lyme disease), meningococcal infection, disseminated gonococcal infection, and travel related illnesses (Malaria, Dengue fever, Typhoid/paratyphoid (enteric fever), Zika and Chikungunya). The patient was diagnosed with Salmonella typhi (enteric fever).


Enteric Fever Pearls:

  • Classically caused by Salmonella enterica serotype Typhi, however other serotypes including S. enterica Paratyphi A, B, or C can cause a similar syndrome.1
  • Typhoid and enteric fever can be used interchangeably
  • More common in children and young adults
  • Most prevalent in poor areas with overcrowding and poor access to sanitation (south-central Asia, Southeast Asia, and southern Africa have the highest incidence of S. Typhi infection).
  • US has ~ 200-300 cases of S. Typhi per year (80% of these cases are in travels to countries where enteric fever is endemic). 2

Clinical Presentation:

  • Classic presentation includes fever, abdominal pain, constipation/diarrhea, “rose spots” (salmon-colored macules on trunk and abdomen), and headaches. Less common manifestations include cough, arthralgias/myalgias, intestinal perforation, and neurologic manifestations (encephalopathy, acute psychosis, myelitis, and disorded sleep patterns).1
  • Symptoms begin ~ 5-21 days after ingestion of the causative organism (typically through contaminated water or food).
  • Common laboratory derangements include cytopenias – anemia, leukopenia (leukocytosis more common in children), and elevated liver enzymes.


  • Must have high clinical suspicion in patients who have traveled to endemic areas.
  • Blood and stool cultures should be obtained. Blood cultures are 40-80% sensitive. Stool studies have a 30-40% sensitivity.1
  • Positive cultures can take several days to incubate, empiric therapy should be started in patients with a high clinical suspicion.
  • Serology testing can be performed, however positive results may represent prior exposure.


  • In patients with severe or complicated disease (organ dysfunction, systemic toxicity, or requires hospitalization), initial therapy with ceftriaxone is appropriate.3
  • In patients with uncomplicated disease who can be treated as an outpatient, fluroquinolone or azithromycin is first line.3
  • Multi-drug resistant strains of S.Typhi are prevalent worldwide. These strains can be commonly resistant to ampicillin, trimethoprim-sulfamethaxazole, and chloramphenicol. Increasing resistance to fluroquinolones is also a growing issue, particularly in South Asia.3



  1. Parry CM, Hien TT, Dougan G, et al. Typhoid fever. N Engl J Med 2002; 347:1770.
  2. Lynch MF, Blanton EM, Bulens S, et al. Typhoid fever in the United States, 1999-2006. JAMA 2009; 302:859.
  3. Kariuki S, Gordon MA, Feasey N, Parry CM. Antimicrobial resistance and management of invasive Salmonella disease. Vaccine 2015; 33 Suppl 3:C21.

Metformin and B12 deficiency

Today at VA Morning Report, a question came up about metformin and B12 deficiency and how often to screen for B12 deficiency in patients being treated with metformin. The short answer is that there are no set guidelines. The long answer is:

Metformin has been reported to cause a decrease in serum B12 concentrations. Cross-sectional studies report a wide range of prevalence of biochemical vitamin B12 deficiency with metformin exposure, ranging from 5.8% to as high as 40%. Though the exact mechanism is not known, it is thought to be caused by B12 malabsorption: it is thought that metformin interferes with the calcium-dependent membrane action responsible for vitamin B12-intrinsic factor absorption in the terminal ileum.

A recent report from the Diabetes Prevention Program (DPP) / DPP outcomes study (DPPOS) assessed the risk of B12 deficiency with metformin. The study contained adult participants from 27 centers in the US. Patients treated with metformin 850 mg BID vs placebo. B12 levels were assessed at 5 years (n = 857, n = 858) and 13 years (n = 756, n = 764). Low B12 (≤ 203 pg/mL) occurred more often in the Metformin group than the Placebo group at 5 years (4.3 vs 2.3%; P = .02) but not at 13 years (7.4 vs 5.4%; P = .12). Combined low and borderline-low B12 (≤ 298 pg/mL) was more common in metformin group at 5 years (19.1 vs 9.5%; P < .01) and 13 years (20.3 vs 15.6%; P = .02). Anemia prevalence was higher in metformin group but did not differ by B12 status. The prevalence of neuropathy was higher in the metformin group with low B12 levels. In the patients with biochemical B12 deficiency, homocysteine levels were was elevated consistent with true B12 tissue deficiency.

Several researchers globally have made recommendation to screen those with T2DM on metformin for B12 deficiency. The group above proposed screening for B12 deficiency prior to initiating metformin (>/= 3-4 years), use of high doses of metformin (>/= 2 g/day), clinically worsening diabetic distal polyneuropathy in the presence or absence of anemia. The most recent American Diabetes Association Standards of Medical Care in Diabetes – 2018 makes the following statement: “Long-term use of metformin may be associated with biochemical vitamin B12 deficiency, and periodic measurement of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy.” (Grade B). No formal recommendations have been provided by USPSTF.

Please refer to this article for more information! Vanita R. Aroda et al and the Diabetes Prevention Program Research Group. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016 Apr; 101(4): 1754–1761.

Cox Conference July 5

Cox’s Conference: Libman-Sacks Endocarditis

In this week’s Ambulatory Cox’s Conference, Dr. Vishnu Prathap presented a case of a female with history of systemic lupus erythematosus (SLE) who presented with a chief complaint of shortness of breath. Our expert discussant and program director, Dr. Dino Kazi guided us through the differential diagnosis for shortness of breath in a patient with SLE.

In a patient with SLE, the differential for shortness of breath is broad due to the wide range of clinical manifestations. Our differential diagnosis included thromboembolic disease (due to possible antiphospholipid syndrome), renal failure (possible lupus nephritis), pulmonary vasculitis, pleuritis with effusion, interstitial lung disease, pulmonary hypertension, myocarditis/pericarditis, pericardial effusion, premature coronary artery disease, and valvular heart disease. Our patient was found to have vegetations on both the posterior and anterior leaflets of the mitral valve with associated severe mitral stenosis. She was diagnosed with Libman-Sacks Endocarditis and the shortness of breath was attributed to valvular heart disease.

Libman-Sacks Endocarditis Pearls:

  • Sterile, valvular vegetations of fibrous tissue made up of proliferating endothelial cells, myocytes, and mono-nuclear cells.1
  • Valvular vegetations are not uncommon in patients with SLE. In a study of asymptomatic patients with SLE, valvular vegetations were found in 7 to 11% of patients on transthoracic echocardiography and 43% of patients on transesophageal echocardiography .2,3
  • Left sided valves are most commonly affected with the mitral valve more commonly involved.
  • Risk factors include presence of lupus nephritis, antiphospholipid antibodies, and high disease activity.

Clinical Presentation:

  • Often times the vegetations are small and clinically silent, however some patients can develop significant valvular disease, valvular heart failure, or systemic embolic phenomena.
  • Severe valvular regurgitation and heart failure symptoms occur in ~ 10% of patients with SLE who have valvular lesions.3,4


  • Thorough history and physical exam (cardiac murmurs, splinter hemorrhages, or other evidence of embolization)
  • Echocardiography – transesophageal echocardiogram more sensitive
  • Rule out infectious endocarditis with blood cultures


  • Anticoagulation is indicated if there is no contraindication and should be continued indefinitely.
  • Surgical intervention in select cases.
  • Treatment of underlying disease. However steroids or cytotoxic therapy have no known effect on the valvular lesions.
  • Antibiotic prophylaxis is appropriate during dental procedures or when patients are suspected to be transiently bacteremic.


  1. Eiken PW, Edwards WD, Tazelaar HD, McBane RD, Zehr KJ. Surgical pathology of nonbacterial thrombotic endocarditis in 30 patients, 1985-2000. Mayo Clin Proc 2001;76:1204-1212
  2. Moyssakis I, Tektonidou MG, Vasilliou VA, et al. Libman-Sacks endocarditis in systemic lupus erythematosus: prevalence, associations, and evolution. Am J Med 2007;120:636-642
  3. Roldan CA, Shively BK, Crawford MH. An echocardiographic study of valvular heart disease associated with systemic lupus erythematosus. N Engl J Med 1996;335:1424-1430
  4. Tarter L, Yazdany J, Moyers B, et al. The Heart of the Matter. N Engl J Med 2013; 368:944-950.


CAR-T Review

The advent of CAR-T cells represent one of the most novel improvements in the treatment of cancer in several decades.

In this week’s New England Journal of Medicine, Dr. June publishes a review on CAR-T cells and their efficacy and toxicities. As CUH has recently begun offering this therapy to select patients with multiple myeloma, this is a great read for anyone rotating through the BMT and MICU services.

The article can be accessed here.

Morning Report July 5 – QI/HVC: Echocardiograms in Patients with Syncope

Today’s morning report was part of our quality improvement morning report series. The lecture was based on this article published in the Journal of Hospital Medicine by Madeira and colleagues.


The case they present is a middle-aged woman who presented following a witnessed syncope with no lingering effects. The patient had no cardiac history a normal exam, normal EKG, and normal labs. The question that was posed is “Does my patient need an echo?”

Syncope is responsible for 1% of all ED visits in the US and is independently associated with increased all-cause mortality. The goal of investigating into causes of syncope is to identify modifiable underlying causes with particular attention to cardiac causes of syncope.

The approach to these patients has been made clearer following the publication of the ACC/AHA/HRS guidelines published in 2017 (featuring Dr. Link of the Division of Cardiology @ UTSW).



In patients with syncope, all should receive a history, physical examination, and EKG. The history should be performed carefully with particular attention paid to cardiac risk factors. EKGs are widely recommended due to the availability, ease of performing, low cost, and lack of risks to the patient. EKGs may identify arrhythmogenic substrates, WPW, Brugada syndrome, long QT syndrome, HCM, and arrhythmogenic right ventricular cardiomyopathy. Other than these, however, there are doubts as to the utility of EKG in subsequent management of patients and prognostic use of EKGs.

But after EKGs, how do we know if our patient needs an echocardiogram?

Data suggest that echos are performed in 39-91% of patients presenting with syncope. Most common reasons (and those elicited during morning report) are for evaluation of depressed ejection fractions, aortic stenosis, pulmonary hypertension, and hypertrophic cardiomyopathy. However, these findings in patients without any known cardiac history are only identified in 3% of patients presenting with syncope. It has been estimated that $60,000-132,000 would need to be spent to find one new significant abnormality if all patients without a cardiac history received an echocardiogram in order to identify one significant abnormality.

However, the diagnostic utility of echocardiograms does increase in patients with a cardiac history or abnormal EKG – 27% of patients with known cardiac history or abnormal EKG were found to have an EF<40%.

So how should we approach patients with syncope? All patients should have a careful history and physical exam, with attention paid to findings suggestive of cardiac disease. All patients should have an EKG and orthostatic vital signs. Echocardiograms should only be performed in patients with known cardiac disease or findings suggestive of a cardiac cause of syncope.

J Hosp Med. 2017 Dec;12(12):984-988. doi: 10.12788/jhm.2864. Epub 2017 Oct 18

Heart Rhythm. 2017 Aug;14(8):e155-e217. doi: 10.1016/j.hrthm.2017.03.004. Epub 2017 Mar 9

J Am Coll Cardiol. 2001;37(7): 1921-1928

Morning Report July 3 – Tenofovir and Osteoporosis

For the last two days, the topic of tenofovir and the risk of osteoporosis has been discussed at the VA morning report.

In general, patients with HIV have a 3-4 times increased risk of developing osteoporosis compared to those without HIV. In vitro experiments have demonstrated viral proteins induce osteoclastic activation and osteoblastic dysfunction, potentially through TNF-a- and IL-6-mediated mechanisms.

However, with initiation of ART, bone mineral density decreases 2-6% over the course of 96 months. Tenofovir, a NNRTI, is increasingly used as first-line therapy in patients receiving ART and in patients receiving PrEP.

In addition to interfering with HIV DNA polymerase, tenofovir also acts directly on the proximal renal tubular cells to decrease phosphate resorption resulting in renal phosphate loss. Tenofovir has also has been associated with elevated PTH, particularly among patients who also had concomitant vitamin D deficiency. Further, even in the absence of HIV infection, tenofovir still produced a small (but significant) decrease in bone mineral density in a prospective study, further supporting a possible direct effect of the drug.

While the mechanism is still incompletely understood, it is important to address risk factors for osteoporosis in this population. Currently, it is recommended to obtain baseline bone densitometry in postmenopausal women and men aged 50 and older with HIV.



Liu, AY, et. al. PLoS One. 2011; 6(8): e23688.

Brown, TT et. al. J Acqu Immune Defic Syndr. 2009 Aug 15:51 (5): 554-61

Rosenvinge, MM, et. al. J Acquir Immune Defic Syndr. 2010 Aug;54(5):496-9.

Brown, TT et. al. Antivir Ther. 2011 16(7); 1063-72

Aberg, JA. Clin Infect Dis. 2014;58(1):e1.

Morning Report July 2 – Hypercalcemia

This morning, a case of hypercalcemia from sarcoidosis was presented in morning report at Parkland.

Sarcoidosis is a multisystem disease of noncaseating granulomas involving two or more organs. The cause of sarcoidosis remains unknown but is felt to be a result of infectious or noninfectious agent that causes an immune response (P acnes and mKatG from Mycobacterium tuberculosis are under investigation).

The granulomas are formed through a complex process. Macrophages present the antigen to CD4 T cells  via the HLA-CD4 complex. Macrophages release IFN-g, IL-12, IL-18, and TNF, CD4 t-cells then release IL-2 and IFN-g, supporting the formation of granulomas.

Hypercalcemia occurs in about 10% as a result of autonomous 1,25-dihydroxyvitamin D production from the granulomas. This 1,25-dihydroxyvitamin D is identical to vitamin D the body otherwise produces and results in increased intestinal calcium absorption, resulting in hypercalcemia with suppressed PTH. Further, this can worsen with sunlight and with exogenous vitamin D, although the latter is still under investigation.

Other causes of 1,25-dihydroxyvitamin D-mediated hypercalcemia include granulomatous disease (tuberculosis, Hansen’s disease, silicosis), lymphoma, Crohn’s disease, histoplasmosis, and granulomatosis with polyangiitis.

The patient in question was treated with high-dose steroids with which her hypercalcemia improved. She was discharged on a steroid taper for continued outpatient follow-up.



CC BY-SA 3.0,

Source: Harrisons 19e Chapter 390 Sarcoidosis.

UTSW Internal Medicine

%d bloggers like this: