EUH Morning Report: Do specific blood pressure medications lead to higher prevalence of Orthostatic Hypotension syncope or recurring syncope in older adults with dementia?

The Bottom Line: In older adults with dementia, nitrates and alpha-blockers alone and the combinations of ACE-Is and diuretics, alpha-blockers and diuretics, and ACE-Is and nitrates are more frequent in patients with syncope due to OH than in those without (Testa et al, 2018).

References: Testa G, Ceccofiglio A, Mussi C, Bellelli G, et al. Hypotenstive drugs and syncope due to orthostatic hypotension in older adults with dementia (syncope and dementia study). J Am Geriatr Soc. 2018 Aug;66(8):1532-1537. Doi:10/1111/jgs.15421.

Ungar A, Mussi C, Nicosia F, et al. Etiology of syncope and unexplained falls in elderly adults with dementia: Syncope and Dementia (SYD) Study. J Am Geriatr Soc. 2016 Aug;64(8):1567-1573. Doi:10.1111/jgs.14225.

Summary: The recent Syncope and Dementia (SYD) Study found that syncope due to OH was the most common type (50%) of syncope in a population of older adults with dementia and recurrent syncope. Additionally, in nearly half of the study’s participants, dementia was vascular in origin (Unger et al, 2016). Aggressive blood pressure treatment has been related to OH, although the role of specific drugs and combinations is unclear (Testa et al, 2018).

Testa et al (2018) found that the number of drugs administered and particular hypotensive drugs, specifically nitrates alone and combinations of ACE-Is and diuretics and of ACE-Is and nitrates, significantly increase the risk of syncope due to OH. Testa et al (2018) recommend using extreme caution when using these drugs in older adults with dementia.


EUH Morning Report: Should lasix (furosemide) be considered in the setting of hypercalcemia?

The Bottom Line: Avoid loop diuretics in the setting of acute hypercalcemia, except it may be considered for patients with concomitant volume overload.

DynaMed Plus provides the following information on loop diuretics:

  • inhibits calcium resorption in distal renal tubule
  • may worsen volume depletion and electrolyte derangements and should be used with caution
  • no evidence to support use in acute hypercalcemia
    • may be used to control volume overload
    • associated with hypokalemia and possibly contributes to dehydration

References: DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 116018, Hypercalcemia; [updated 2016 Dec 27, cited 2018 Jul 19]; [about 10 screens]. Emory login required.

LeGrand SB, Leskuski D, Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Annals of Internal Medicine. 2008;149(4):259-263.

Summary: The following is a review of LeGrand et al’s 2008 article (NEJM Journal Watch):

A literature review found little support for the use of the diuretic furosemide to treat hypercalcemia.

Many textbooks recommend saline and furosemide as first-line management for hypercalcemia. Investigators searched the literature since 1950 for studies of furosemide or bisphosphonate use for hypercalcemia in people.

They identified nine reports — the most recent from 1983 — involving 37 patients treated with furosemide for hypercalcemia; doses ranged from 240 mg to 2400 mg. Calcium normalized in 14 of 39 episodes, and within 12 hours in only two cases. Intensive monitoring was accompanied by replacement of fluid and electrolyte losses. Complications included hypernatremia, coma, metabolic acidosis, hypophosphatemia and hypomagnesemia, altered mental status, and tetany.

Investigators identified 56 clinical studies of bisphosphonates — 34 were randomized and included more than 1000 patients. In a systematic review of 26 studies of bisphosphonate use in hypercalcemia of cancer, calcium levels normalized in more than 70% of patients. The authors conclude that volume repletion and bisphosphonate therapy should be the standard management strategy for hypercalcemia, with furosemide used only for managing fluid overload.


Forced saline diuresis for hypercalcemia is a long-standing practice that persists, even in authoritative texts, despite the absence of evidence for its efficacy, the existence of known risks, and the availability of other proven treatments. Saline and bisphosphonates, with or without calcitonin, are the standard of care for hypercalcemia.

EUH Morning Report: What is Sister Mary Joseph’s nodule?

The Bottom Line: Sister Mary Joseph’s nodule is a metastatic cancer of the umbilicus that is typically associated with adult cancers of the gastrointestinal tract and ovary (Albano and Kanter, 2005). It is a rare but important physical finding and is a sign of advanced stage of malignancy (Tso et al, 2013).

References: Albano EA, Kanter J. Sister Mary Joseph’s Nodule. N Engl J Med. 5 May 2005;352(18):193.

Tso S, Brockley J, Recica H, Ilchyshyn A. Sister Mary Joseph’s Nodule: an unusual but important characteristic of widespread internal malignancy. Br J Gen Pract. 2013 Oct;63(615):551-552. Doi: 10.3399/bjgp13X673900.

Summary: The condition is named after Sister Mary Joseph (1856-1939), a surgical assistant for Dr. William Mayo, who noted the association between paraumbilical nodules observed during skin preparation for surgery and metastatic intraabdominal cancer confirmed at surgery (Albano and  Kanter, 2005).

EUH Hunt Conference: What is the prognosis for adenocarcinoma of the lung?

The Bottom Line: There is an overall survival rate of less than 5 years.

  • Stage I: 68-92%
  • Stage II: 53-60%
  • Stage III: 13-36%
  • Stage IV: 0-10%

Reference: DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 114774, Non-small cell lung cancer; [updated 2018 May 01, cited 15 May 2018]; [about 31 screens]. Emory access required.

Summary: Five-year survival is only 5-8% in patients with unresectable NSCL cancer. Patients with untreated T1 tumors have a survival rate of 9%. Five-year mortality is higher in men than in women.

5-year survival for patients with lung and bronchus cancer by stage at diagnosis:

  • 18% with disease at all stages
  • 55% with localized disease
  • 28% with regional disease
  • 4% with distant stage disease

A study considering intervention and age found that older age and less intervention is associated with poorer survival:

  • > 80 years: 47% no radiation/surgery, 7.4% 5-year survival
  • 70-79 years: 28% no radiation/surgery, 12.3% 5-year survival
  • < 70 years: 19% no radiation/surgery, 15.5% 5-year survival

Additional Information: DynaMed Plus provides breakdowns by stage, age, and other factors.

For information on the staging of lung cancer, see the IASLC Lung Cancer Staging Project.

EUH Hunt Conference: A review of Horner syndrome

The Bottom Line: Horner syndrome results from an interruption of sympathetic innervation to the eye. The classic triad is unilateral ptosis (slight narrowing of the ocular fissure), miosis (smaller pupil on the affected side), and anhidrosis (lack of perspiration on the forehead or face). Horner syndrome is not likely to cause any functional visual disturbance but is of great importance clinically as a “red flag” warning that the oculosympathetic pathway has been interrupted and thus there may be potentially life-threatening lesions in the head, neck, and chest.

Reference: Martin TJ. Horner syndrome: a clinical review. ACS Chem Neuroscience. 2018 Feb 21;9(2):177-186. Doi:10.1021/acschemneuro.7b00405

Summary: The first, and perhaps most important, aspect of evaluating suspected Horner syndrome is a careful history. The history often reveals an obvious cause, such as trauma or neck/chest surgery, or will show that the Horner syndrome had been present for many years and therefore may not require an extensive investigation. The history may also reveal other symptoms that would help localize the lesion causing the Horner syndrome. A careful examination is obviously also critical, as other causes of anisocoria or ptosis may need to be considered rather than Horner syndrome, and concomitant signs (for example, a sixth nerve paresis) may help localize a potential lesion. After this, pharmacologic testing can be helpful to confirm diagnosis. Many clinicians will elect not to evaluate Horner syndrome if it has been present for greater than two years.

Though often benign or idiopathic, the cause of Horner syndrome can be very threatening or even lethal, so understanding how to recognize, diagnose, and appropriately evaluate Horner syndrome is important to all clinicians.

Krakow Conference: What are therapy options for DRESS syndrome?

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a rare, severe cutaneous adverse reaction characterised by fever, rash, lymphadenopathy, eosinophilia and/or other leukocyte abnormalities, and internal organ involvement and often has a relapsing–remitting course despite withdrawal of the drug.

Fernando, S.L. (2013). Drug-reaction eosinophilia and systematic symptoms and drug-induced hypersensitivity syndrome. Australasian Journal of Dermatology, 55(1), 15-23. .

The French Society of Dermatology formulated guidelines on the management of DRESS/DIHS as follows:

1. Absence of signs of severity: topical corticosteroids, emollients and H1-antihistamines.

2. Presence of signs of severity (transaminases > fivefold normal, renal impairment, pneumonia, haemophagocytosis and cardiac involvement): prednisone 1 mg/kg per day.

3. Life-threatening signs: (haemophagocytosis with bone marrow failure, encephalitis, severe hepatitis, renal failure, respiratory failure): prednisone and i.v. Ig 2 g/kg over 5 days.

4. Presence of signs of severity with confirmation of major viral reactivation: prednisone and valgangciclovir +/− i.v. Ig

EUH Dressler Conference: What are HIV elite controllers and HIV long-term nonprogressors?

The Bottom Line: Long-term nonprogressors (LTNP) account for 1-5% of HIV-infected individuals characterized by documented infection for more than 7-10 years, a stable CD4+ T cell count over 500/mm3 and low viremia in the absence of antiretroviral treatment. They are able to remain clinically health for more than 10 years in the absence of ART (Lugue et al, 2014).

Elite controllers (EC) are a small number of untreated HIV-1-postivite patients (approx. 1 in 300 infected people) who have undetectable viral loads in commercial PCR assays. Most definitions of EC require HIV-1 replication to be below the level of detection on at least three occasions during a 12-month period. Epidemiological studies have shown that the spontaneous control of HIV-1 replications can last more than 30 years, although loss of immune control is observed in some individuals (Walker and Yu, 2013).

References: Luque MC, Santos CC, Mairena EC, Wilkinson P, et al. Gene expression profile in long-term non progressor HIV infected patients: In search of potential resistance factors. Mol Immunol. 2014 Nov;62(1):63-70. doi:10.1016/j.molimm.2014.05.016.

Walker BD and Yu XG. Unravelling the mechanisms of durable control of HIV-1. Nat Rev Immunol. 2013 Jul;13(7):487-98. doi:10.1038/nri3478.

Summary: From “Genetics of HIV” [chapter 84] in Clinical Genomics: Practical Applications in Adult Patient Care (via AccessMedicine):

Long-term Nonprogressors: A significant number of studies have evaluated this population and among this group, the CCR5 mutations are most well characterized in terms of their ability to prevent HIV acquisition and delay AIDS progression through impaired HIV entry into cells. The Δ32 variant is the most prevalent mutation in this population and has been demonstrated to have prevalence in these individuals of 30%. It is on the basis of this understanding that the entry inhibitor class of antiretrovirals has been developed. By contrast, some mutations that interact or inhibit or downregulate CCR5 are associated with accelerated progression to AIDS. HLA typing subsets have also been implicated in this group, specifically related to individuals with the HLA-B*5705 and HLA-B*2705 who demonstrate substantially longer HIV course before progression to AIDS. In small sample sizes greater than 80% of LTNPs posses these alleles compared with approximately 10% of chronic progressors. An additional class of LTNPs has been identified who suppress viral progression on the basis of antibodies to HIV surface proteins including gp120 and gp41.

Elite Controllers/Suppressors: The APOBEC group of genes is important in the study of long-term nonprogressors and elite controllers, as mutations in APOBEC3G have been shown to relate to delayed AIDS progression. This group of proteins is made up of cytidine deaminases that catalyze the deamination of cytosine to uracil in the nascent viral DNA causing mutations that are lethal for the virus. HLA complex P5 (HCP5) has been implicated as associated with 1% of HIV patients who demonstrate slowed progression of disease. The HCP5 gene is located on chromosome 6, and the associated variant is known to be in high linkage disequilibrium with the HLA allele B*5701. HLA-B*57 and B*58 are associated with low viral load that is thought to boost cytotoxic T-lymphocyte activity. KIR3DS1 or KIR3DL1 allele and HLA class I alleles that encode an isoleucine at position 80 (HLA-Bw480I) had the slowest rates of progression to AIDS.

For additional reading: Madhavi V, Wines BD, Amin J, Emery S, et al. HIV Env- and Vpu-specific antibody-dependent cellular cytotoxicity responses associated with elite control of HIV.  J Virol. 2017 Aug 24; 91(18): pii:e00700-17. doi:10.1128/JVI.0700-17.

Pereyra F, Addo MM, Kaufman DE, Liu Y, et al. Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy. J Infect Dis. 2008 Feb 15;197(4):563-71. doi:10.1086/526786.

EUH Hunt Conference: What is plastic bronchitis?

The Bottom Line: Plastic bronchitis (PB) is an uncommon pulmonary disease characterized by production of cohesive and branching casts filling the airways. The diagnosis of PB is confirmed by a history of expectoration of branching airways casts, or by removing branching casts at the time bronchoscopy. Life-threatening respiratory distress can occur because of obstruction of airways with casts in children with congenital heart disease or as a consequence of lymphatic engorgement following surgical correction of congenital heart disease (Rubin 2016).


Figure: Typical expectorated branching cast from a child with plastic bronchitis caused by congenital heart disease (Rubin 2016).

Reference: Rubin BK. “Plastic bronchitis.” Clinics in Chest Medicine. 2016 Sept; 37(3): 405-408.

Summary: Key points as outlined by Rubin (2016):

  • Plastic bronchitis associated with congenital heart disease or with lymphatic anomalies is caused by aberrant pulmonary lymphatic vessels and drainage. This true form of plastic bronchitis can usually be treated by selective lymphatic vessel ablation.
  • Plastic bronchitis is probably more common than reported. This speculation is based on the observation that many clinicians are unfamiliar with the disease and may fail to recognize milder forms of the syndrome.
  • Plastic bronchitis with cohesive branching airway casts should not be confused with the more common, but smaller and more etiologically distinct, casts that are associated with mucus plugging.
  • For nonlymphatic plastic bronchitis associated with eosinophils and Charcot-Leyden crystals within casts, the most effective therapy seems to be cast removal followed by high-dose or pulse corticosteroids.

EUH Dressler Conference: For how long does the Hepatitis B vaccine provide protection?

The Bottom Line: The duration of protection in children and adults resulting from hepatitis B vaccination is unknown. In a 30-year study done on 1528 Alaska Natives it was found, based on anti-HBs level ≥10 mIU/mL at 30 years and an 88% booster dose response, that ≥90% of participants had evidence of protection 30 years later. Booster doses are not needed.

Reference: Bruce MG, Bruden D, Hurlburt D, Zanic C, et al. Antibody levels and protection after hepatitis b vaccine: Results of a 30-year follow-up study and response to a booster dose. Journal of Infectious Diseases. 2016 July; 214(1): 16-22. Doi: 10.1093/infdis/jiv748.

Summary: Among 243 persons (56%) who responded to the original primary series but received no subsequent doses during the 30-year period, 125 (51%) had an anti-HBs level ≥10 mIU/mL. Among participants with anti-HBs levels

EUH Krakow Conference: How prevalent are autoimmune diseases in HIV patients?

The Bottom Line: The spectrum of autoimmune diseases associated with HIV infection seems to be unexpectedly wide, involving several organs, such as lungs (sarcoidosis), thyroid gland (Graves’ disease), liver (autoimmune hepatitis), connective tissue (systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa and other types of vasculitis, antiphospholipid syndrome) or hematopoietic system (autoimmune cytopenias).

Reference: Roszkiewicz J and Smolewska E. Kaleidoscope of autoimmune diseases in HIV infection. Rheumatology International. 2016 Nov; 36(11):1481-1491.

Summary: The coincidence of autoimmune diseases in the setting of immunocompetence loss during HIV infection may seem paradoxical. Nevertheless, the list of diseases with underlying autoimmune mechanism is long and, as a matter of fact, almost every organ of the body can be affected by the immune process. The occurrence of a particular autoimmune disease depends on degree of immunosuppression of the HIV-positive patient. As the clinical manifestations of autoimmunization often mimic those inscribed in the course of HIV infection, health care providers should be aware of this rare but potentially deadly association and actively seek for its symptoms in their patients.