1. health and fitness
2. disease

Issue 25 | November 2014
NAAMA MEDICAL NEWSLETTER
Dear Members and Friends,
It is my pleasure to send you
the 25th issue of NAAMA
Medical Newsletter. I hope
the information included in
this issue will further help you
to deliver better care to your
patients. If you have any
questions or comments don’t hesitate
to contact me at 917 921-1833 or
email me at [email protected].
Nidal Isber, MD, FACC, FHRS
Director, Cardiac
Electrophysiology Services
Richmond University Medical Center
Staten Island, New York
Cover, oil painting by artist Rami Sabour
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Issue 25| November 2014
COLOGUARD, A NEW STOOL DNA TEST ACCURATELY DETECTS COLON
CANCER AND ADVANCED ADENOMA
Colonoscopy
is the gold
standard
test
for colon cancer screening.
Guidelines recommend that all
adults age 50 to
75 years old be
screened. Colonoscopy use has tripled in the past decade which resulted
in 30% reduction in the numbers of colon cancer. However, there are 25 million adult candidates for screening that
do not get colonoscopies, partly due to colonoscopy’s Invasive nature and inconvenience. The FDA has approved
an innovative non-invasive screening test that could be
a good alterntive option to colonoscopy. Cologuard is a
stool-based test that is designed to detect the presence
of hemoglobin and certain DNA mutations in cells shed
by advanced adenomas. The FDA approval was based on
a study published in New England Journal of Medicine
(
). The study included 10,000 subjects who
were screened by Cologuard. The test was 92% effective
for detecting colon cancer and 94% effective at detecting
early stage cancer (I, II) when tumors are most curable.
The test was also effective in detecting 42% of advanced
adenoma while fecal immunochemical test (FIT), an already approved test, detected 74% of cancer and 24%
of advanced adenoma. Patients with positive Cologuard
are advised to undergo a diagnostic colonoscopy. On the
same day the FDA approved the Cologuard, the CMS has
proposed National Coverage. (NEJM 2014; 370:1287).
EATING 10 PORTIONS OF TOMATOES A WEEK SIGNIFICANTLY REDUCES
THE RISK FOR PROSTATE CANCER
Dietary and lifestyle changes may reduce the risk for
cancer. In this study, researchers assessed the effect
of dietary and lifestyle changes specifically on prostate
cancer (PC) risk. Guidelines published 8 recommendations for cancer prevention. These include 1) be as
lean as possible, 2) be physically active, 3) avoid sugary
drinks, 4) eat more vegetables and fruits, whole grains
and legumes, 5) limit consumption of red meat and avoid
processed foods, 6) limit alcohol consumption, 7) avoid
salt, 8) do not use supplements to protect against cancer.
Researchers investigated whether adherence to recommendations is associated with PC risk. The study included 1800 men with PC (ages 50-69 years) who were
compared with 12,000 men without cancer. Results
showed that greater adherence to recommendations to
increase plant foods and tomato products were inversely
associated with overall risk for PC. Men who ate over
10 portions of tomatoes and tomato products, such as
tomato sauce, had an 18% reduced risk for developing
PC. The findings suggest that tomatoes may be important in PC prevention. Tomatoes are rich in lycopene,
a carotenoid that gives fruits and vegetables a red color.
Lycopine has been linked previously to improved blood
vessel function in cardiovascular disease patients. (Cancer Epidemiology, Biomarkers and Preventions 2014).
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Issue 25| November 2014
SYNCOPE DUE TO SUBCLAVIAN
STEAL SYNDROME
A 58-year-old female
was referred for evaluation of near syncope and
fall. The patient had a
history of hypertension,
diabetes and coronary
artery disease with stent
placement in the right
coronary artery. The patient was on Metformin, Ace-inhibitor, beta blocker, statin and aspirin. The patient for
a year had been complaining of left arm pain when doing
physical activity using that arm which was attributed to
arthritis. The patient also complained of dizziness when
doing activities that require raising her left arm over her
head. A week prior to evaluation, the patient experienced
an episode of blurred vision, vertigo and dizziness that resulted in a fall when she was cleaning the upper shelf of
her kitchen cabinet. Patient denied losing consciousness.
On physical examination, her blood pressure in the left
arm was 90/60 and in the right arm 120/80. Based on
the patient’s symptoms and the difference in blood pressure between her two arms, the patient was suspected of
having subclavian steal syndrome (SSS). This diagnosis
was confirmed by an aortic arteriography which showed
obstruction of the left subclavian artery with late phase
showing retrograde filling via the ipsilateral posterior
vertebral artery. The disease was treated with carotidsubclavian artery bypass grafting. On several follow-ups
the patient remained asymptomatic. SSS is a rare cause
of syncope and near syncope that is caused by occlusion
or stenosis of the proximal subclavian artery with subsequent retrograde filling of this artery via the ipsilateral
vertebral artery. Symptoms result from vertebrobasilar
insufficiency. These include vertigo, diplopia, blurred vision, syncope and fall. Atherosclerotic plaque that develops in the proximal portion of the subclavian artery
is the most common cause of subclavian obstruction.
Other causes include Takayasu arteritis and congenital anomalies of
the aortic arch.
The diagnosis of
SSS can be confirmed by MRA
or aortic arch
angiography. The
disease is treated
with
carotidsubclavian
bypass or subclavian artery angioplasty and stenting.
ONE HOUR OF MODERATE PHYSICAL
ACTIVITY REDUCES THE RISK OF
HEART FAILURE BY 46%
The American Heart
Association
recommends 150 minutes
of moderately intense
physical activity every
week. Physical activity
lowers many heart disease risk factors. The
association between levels of physical activity and the
risk of heart failure (HF) is little known. Researchers investigated the association of total and leisure time physical activity with the risk of heart failure. The prospective
study included 40,000 participants who were evaluated
in 1997; none of them had HF at the beginning of the
study. Participants were followed until the end of 2010
to see how their activity is related to the risk of developing HF. The results showed that the more active a person
was, the lower the risk of HF. The participants who had
more than 1 hour of moderate exercise or 30 minutes of
vigorous exercise per day had their risk of HF lowered
by 46%. Moderate exercise such as brisk walking, dancing, gardening, housework and domestic chores and active involvement in games and sports with children lowers the risk of HF. (Circulation, Heart Failure 2014).
INCRETIN TREATMENT FOR
DIABETES DOES NOT INCREASE
THE RISK OF PANCREATITIS
Acute pancreatitis is a serious
condition. Incretin-based treatment for type 2 diabetes has been
reported to increase the risk of
pancreatitis. Researchers investigated the risk of pancreatitis associated with the use of incretinbased treatment in patients with type 2 diabetes. In a
meta analysis of 55 trials that included 33,000 patients,
only one out of 1000 patients taking GLP-1 receptor
agonist and DPP-4 inhibitor experienced acute pancreatitis. Incretin-based treatment was not associated with
increased risk of pancreatitis. In a cohort of 73,000
patients, incretin-based drugs were compared with sulfonylureas. No association was found between incretinbased drugs and acute pancreatitis after 1.4 years. The
data indicate that incretin-based treatment for patients
with type 2 diabetes does not increase the risk of pancreatitis. The data should reassure physicians about
the safety of these drugs. (BMJ 2014, 348:g2366).
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Issue 25| November 2014
RECURRENT SYNCOPE DUE TO SYSTEMIC MASTOCYTOSIS
A
43-year-old
male was referred
for evaluation of
syncope of unknown origin. Patient suffered from
syncope for many
years. During an
episode, the patient experiences
flushing of his face, palpitations, shortness of breath and
hypotension which was documented by a family member
who is a nurse, the patient then loses consciousness. On
several occasions, the patient complains of pruritus and
a headache. His symptoms spontaneously disappear after
a short period. He had extensive cardiac and neurologic
work-up done several times without revealing the etiology of syncope. Because of his complaint of flushing, the
patient underwent work-up for carcinoid syndrome, thyroid medulary carcinoma and pheochromocytoma with
negative results. These tests included urine 24 hour collection for 5-hydroxyindolacetic acid (5HIAA), vanillylmandelic acid (VMA), total metanephrins and CT scan
of chest and abdomen. At this time systemic mastocytosis (SMC) was considered in the differential diagnosis
of flushing and hypotension. Therefore, bone marrow
biopsy and bone scan were ordered which were diagnostic of SMC. Bone marrow showed spindle appearance
of mast cells and bone scan showed increased bone activity. Diagnosis of SMC was made and the patient was
treated with H1 and H2 blockers to block histamines.
He was also given high doses of aspirin to block prostaglandin synthesis. Subcutaneous epinephrine is used to
abort an acute vasomotor attack. The patient remained
asymptomatic on follow-ups 18 months after treatment.
SMC is a rare neoplastic disease that is characterized by
abnormal proliferation of most cells and their CD34T
that may infiltrate various organs, including skin, gastrointestinal, liver, spleen, bone marrow and lymph nodes.
SMC should be included in the differential diagnosis of
unexplained recurrent syncope that is associated with
flushing. Flushing is caused by the release histamines and
vasoactive prostaglandins (PGD2). Most of the symptoms of SMC are limited to cutaneous manifestations.
Urticaria pigmentosa associated with Dariers sign (wheal
and flare after gently stroking a skin lesion) is considered a pathognomonic signs of SMC. SMC without urticaria pigmentosa is rare. Essentially the diagnosis cannot
be made until a rash is recognized to be urticaria pigmentosa. A biopsy
of the rash confirmed the diagnosis of mastocytosis.
PREMATURE ATRIAL CONTRACTION DETECTED ON ROUTINE EKG
IS ASSOCIATED WITH INCREASED MORTALITY IN HEALTHY INDIVIDUALS
Premature atrial (PAC) and ventricular (PVC) contractions are common cardiac arrhythmias and frequently
detected on routine EKG. These arrhythmias are not
considered by themselves an abnormal finding. Researchers evaluated the prognostic significance of premature ectopic beats (PAC and PVC) diagnosed during 12
Lead EKG in healthy individuals. They reviewed data
on 7500 adults (mean age 60 years) who had normal sinus rhythm and no cardiovascular disease or other EKG
abnormalities. 1.2% of the cohort had PACs and 1.5%
had PVCs. During mean follow-up of 13 years, 2,386
(32%) participants died. All-cause mortality, cardiovascular mortality and ischemic heart disease mortality were
all higher in both the PAC and PVC groups than in the
group with premature ectopic beats. APCs were associated with significant increased risk of 40% for all-cause
mortality, 60% for cardiovascular mortality and 100%
for ischemic heart disease. PVCs were not an indepen-
dent risk factor for any mortality after adjustment for demographic and comorbidity. PACs are often completely
asymptomatic, but occasionally they manifest as a feeling
of skipped beats or a jolt in the chest. The mechanism for
increased risk associated with PACs is unknown. However, it is known that the PACs can trigger atrial fibrillation or atrial flutter. (Am J Cardiol 2014; 114:59).
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Issue 25| November 2014
RECURRENT SYNCOPE IN A PATIENT WITH BOTH CONGENITAL
LONG QT SYNDROME AND VASOVAGAL SYNCOPE
A 25-yearold female
was referred
for the evaluation of recurrent syncope since
she was a
t e e n a g e r.
The patient
had initially
rare episodes but recently her episodes increased in frequency. Her episodes were triggered by emotional stress
and were not preceded by significant warning symptoms
except a few seconds of dizziness that progressed quickly
to loss of consciousness. The patient regained consciousness in a very short period, and she denied any weakness,
nausea, vomiting, seizures or sphincter incontinence.
The patient reported that her mother died suddenly at
age 38. Physical examination was normal. She did not
have orthostatic hypotension. Her echocardiogram was
normal. Her EKG showed normal sinus rhythm with
QTc interval of 480 msec. A tilt table test using Isu-
COMPLETE REVASCULARIZATION HAS
BETTER OUTCOME THAN LESION
ONLY PRIMARY PCI AFTER
MYOCARDIAL INFARCTION
When a patient presents with acute
myocardial infarction, he or she has
30% to 40% chance of having multivessel coronary artery disease on
coronary angiogram. During PCI it
is difficult to predict which lesion
will go on to cause events vs. lesions that will remain stable. Current guidelines recommend “staged” procedure:
to deal with urgent lesions, then schedule patients for
treatment of other lesions at a different time. Researchers
conducted a study to compare the outcome of complete vs.
infarct-related artery (IRA) only PCI. In their CULPRIT
trial researchers randomized 146 primary PCI patients to
treatment of IRA only and 150 patients to complete revascularization that treated the culprit plus any other artery
> 70% stenosis at the time of the primary PCI. The study
showed a striking benefit for complete revascularization
in these patients. There was a 65% reduction in major
adverse cardiovascular events over a mean follow-up of 23
months with total vs. culprit artery PCI. The results will
be considered in future guidelines. (ESC 2014 Congress).
prel was positive for vasovagal syncope. The patient was
placed on beta blocker with a decrease in her symptoms.
However, because of her family history of sudden cardiac death and because her EKG showed slight prolongation of QT an insertable loop monitor was implanted
to rule out an arrhythmic cause. Three months later,
the patient reported a pre-syncopal episode. Interrogation of the insertable loop monitor showed an episode of
polymorphic ventricular tachycardia. The combination
of slightly prolonged QT on 12 lead EKG and the presence of polymorphic ventricular tachycardia recorded on
the loop monitor along with a family history of sudden
cardiac death is highly suggestive of congenital long QT
syndrome LQTS. In this case the patient had a positive
tilt table test for vasovagal syncope. The lack of significant warning symptoms is consistent with an arrhythmic
cause for syncope. However, some patients with vasovagal syncope may develop asystole rapidly that leads
to syncope without prodromal symptoms. The patient’s
syncopal episodes were triggered by emotional stress
which points to both vasovagal response and arrhythmic cause. The presence of family history in this patient
prompted the implantation of the insertable lop recorder
to correlate future episodes with EKG recordings. The
patient received an ICD to prevent sudden cardiac death.
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Issue 25| November 2014
BEE STING AFTER TAKING NONSTEROIDAL ANTIINFLAMMATORY
MAY TRIGGER A SYSTEMIC REACTION
An interesting report was published regarding systemic
allergic reaction (SAR) to bee stings in bee keepers after
taking non-steroidal anti-inflammatory drugs (NSAID).
The report described 3 lifelong beekeepers with tolerance to stings. These individuals suffered SAR when
they were stung by bees shortly after taking NSAID. After the episodes, all 3 bee keepers demonstrated tolerance
to stings and to NSAID when exposed to each separately.
The implication for those who are known to have bee allergies is that they are at risk for systemic reactions and
should start immunotherapy. Venom immunotherapy is
effective in 98%. Venom immunotherapy is administered
every 4 to 8 weeks for 5 years. Self injection devices
should be prescribed to patients at risk for this allergic
reaction. SAR occurs in about 1-3% of people with bee
stings and may present with urticaria, angioedema, airway obstruction and hypotension. At least 50 fatal reactions to insect stings are reported each year in the US
and many sting fatalities may not be recognized. 50% of
fatal reactions occur in persons with no history of allergic
sting reactions. In a study of unexplained sudden deaths,
post-partum blood samples often were found to contain
venom specific IgE antibodies and elevated serum tryptase, demonstrating the anaphylaxis pathophysiology of
the fatal episode. Epinephrine is the treatment of choice
for acute anaphylaxis. (Ann Allergy Immunol 2014).
PATIENTS WITH AUTOIMMUNE
RHEUMATOLOGICAL DISEASES
SHOULD BE VACCINATED BEFORE
BIOLOGICAL THERAPY
Both autoimmune rheumatological diseases (AIRD)
and their treatment with biological agents predispose for
infections. Some infections can be prevented by vaccination. Therefore, patients’ vaccination status should
be reviewed prior to starting biological therapy such as
rituximab (which depletes B cell) and tocilizumab (an
anti-tumor necrosis factor). No formal recommendations were published, but a recent review of the subject
provided valuable recommendation for vaccination in
adult patients with AIRD undergoing treatment with
biological agents. Inactivated influenza and pneumococcal vaccines are strongly recommended. The 13-valent
pneumococcal conjugated vaccine PCV13 should be
used first, and then the 23 valent pneumococcal polysaccharide vaccine PPSV23 should be given two months
later and a boost of PPSV23 every 5 years. Tetanus toxoid should be administered as in the general population.
Live attenuated vaccines such as herpes zoster should
be avoided in patients receiving biological therapy but
such vaccine can be given to patients who are taking low
dose steroid (< 20 mg per day) or low dose methotrexate (< 0.4 mg/kg) or both. No guidelines were provided
for human papilloma virus (HPV), hepatitis A, hepatitis B, meningococcal and hemophilia influenza b vaccine
because they have not been studied in this population.
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Issue 25| November 2014
VACCINATION COVERAGE AMONG
ADULTS REMAINS LOW
Vaccinations are an important part of staying healthy.
However, 60% of people think that healthy adults do
not need to be vaccinated. Adult vaccination coverage
in the US remains low. This results in 30,000 deaths
per year from vaccination-preventable disease; 95% of
these deaths are among adults. Several vaccines are recommended for adults. First, all adults should be vaccinated against influenza every year. If not administered
as an adolescent, all adults should receive the one-time
TDAP vaccine, in addition to a booster called Td that
should be administered every 10 years. The TDAP vaccine should also be given to women every time they are
pregnant (between 27-36 weeks gestation). All women
aged up to 26 years should receive HPV vaccine if they
did not have it during adolescence. Men up to age 21
years should also have the HPV vaccine. Pneumococcal vaccine is recommended for all adults aged 65 years
and older. The vaccine protects against pneumonia and
meningitis. This vaccine is also recommended for those
at high risk for pneumococcal disease such as individuals with diabetes, heart disease, lung disease and those
who smoke. The zoster vaccine is recommended for
adults aged 60 and older. Hepatitis B, MMR, varicella
(chicken pox) and meningococcal vaccine may be recommended for health care workers who are more likely to be exposed to a wider array of infective diseases.
Current seasonal influenza vaccine coverage in adults
18 years and older is only 41% and the pneumococcal
vaccine coverage among adults aged 65 years and older
is 60%. Physicians should raise awareness of immunization in adults and they should discuss and encourage their patients to receive recommended vaccines.
WOMEN NEED MORE THAN OB/GYN
FOR PREVENTIVE CARE SERVICES
Guidelines recommend annual well-women visits by OB/
GYN, but it does not state whether OB/GYN should also
serve as primary care. However, it is widely recognized
that OB/GYNs play a part in primary care. Researchers analyzed data on 63 million preventive care visits
to see what services women typically receive during a
well-women visit with a primary care doctor (PCD) compared to an OB/GYN. The study showed that women
who see PCDs for their annual checkup tend to receive
a broader range of services than women who see OB/
GYNs. Women who saw OB/GYNs were more likely to
get screened for cervical and breast cancer, Chlamydia
and OP compared to those who went to PCDs. Those
who went to PCDs were more likely to get screened for
colon cancer, cholesterol, diabetes and to be counseled
about diet, exercise and obesity. Counseling about smoking was low by both OB/GYNs and PCDs. Women of
reproductive age who see OBGYNs only for preventive
care may not be receiving the full spectrum of recommended screenings and counseling. Services that should
be considered during an annual visit include mammogram, breast exam, blood pressure, screening for hypercholesteremia, diabetes, colon cancer, Pap smear,
OP and immunizations. (JAMA intern med 2014).
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Issue 25| November 2014
ANGIOTENSIN-NEPRILYSIN INHIBITOR IS SUPERIOR TO ENALAPRIL
TREATMENT IN HEART FAILURE
The activation of renin-angiotensin-aldosterone system
(RAAS) and adrenergic nervous system plays a central role
in the pathogenesis of heart
failure (HF). The widespread
use of drugs that block these
systems has improved dramatically the survival of patients
with HF. There is an evidence that natriuretic peptide
(NP) system, which mediates a beneficial cardiovascular
effect, is also impaired in HF. Therefore, it was hypothesized that an approach to upgrade NPs may be of therapeutic benefit. A novel drug, angiotensin receptor neprilysin inhibitor (ARNI) was introduced for HF. This drug
targets both neurohormonal systems by inhibiting neprilysin, which prevents natriuretic peptide degradation,
while concomitantly blocking the angiotensin receptors.
Researchers conducted a study to compare ARNI with
enalapril in HF. The study included 8400 patients with
class 2-4 HF with ejection fraction < 40%. Patients were
randomized to receive either ARNI 200 mg twice daily
or enalapril 10 mg twice daily on top of other recommended therapy. At 2 years of follow-up, the primary
outcome of cardiovascular mortality or first hospitalization for HF was reduced by 20% with ARNI compared
with enalapril. Cardiovascular death occurred in 13.3%
of the ARNI group vs. 16.5% of the enalapril group.
The number of patients needed to be treated with ARNI
to prevent one cardiovascular death was 32. This study
indicates that the new angiotensin receptor neprilysin inhibitor is superior to enalapril in patients with HF.
This new class of drugs
may become a standard
of care. (NEJM 2014).
NOCTURNAL SYNCOPE, A RARE CASE OF
MALIGNANT NEUROCARDIOGENIC SYNCOPE
A 30-year-old male was referred for evaluation of recurrent syncope. He reported having 10 episodes over the
past year, all of them occurred while sleeping in bed except for 2 episodes that occurred while the patient was
sleeping in his seat on the airplane. During a typical episode, the patient usually wakes up at night with nausea,
diaphoresis and an urge to defecate, and then he loses
consciousness for less than one minute. After regaining
consciousness, he feels extremely weak and drained of
energy. On one occasion, the patient had incontinence of
urine and feces. On another occasion, he was observed
by his wife to have transient myoclonic jerking. Physical examination, EKG, echocardiogram, and laboratory
tests were all normal. Neurologic evaluation including
EEG and video EEG were normal. A tilt table test was
positive for vasovagal syncope with both vasodepressor
and prominent cardioinhibitory component manifesting
with 11 second ventricular asystole. The patient was
diagnosed with nocturnal malignant vasovagal syncope
and because of the long asystole, the patient received a
dual chamber permanent pacemaker. On follow-up, the
patient reported dramatic improvement in his symptoms.
He no longer had syncope. However he continued to be
awakened with diaphoresis and dizziness. The patient
was treated with beta blocker that further improved his
symptoms. This patient has symptoms that are typical
of vasovagal syncope but because syncope during sleep,
he was suspected to have a seizure disorder, especially
that he was observed to have muscle jerking. Transient
myoclonic jerking is seen frequently in syncope when
severe cerebral hypoperfusion occurs secondary to transient asystole. The patient did not have any of the reliable features of a seizure such as tongue biting, postictal
confusion or hypersomnolence. The unsolved question is
what is the trigger for this patient’s nocturnal syncope?
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Issue 25| November 2014
INFLUENZA VACCINE DURING THE
SECOND HALF OF PREGNANCY
PROTECTS BOTH THE MOTHER
AND THE INFANT
Guidelines
recommend
vaccination of pregnant
women against influenza
to protect both women
and their infants. The vaccine is given in the second
half of pregnancy but only
50% of pregnant women receive it. There is limited data
on the efficacy of vaccination during pregnancy in protecting women and their infants. Researchers followed
2000 women between 20 and 36 weeks of pregnancy
who received intramuscular inactivated trivalent influenza vaccine or placebo. They found that the vaccine
was immunogenic in pregnant women and their infants.
The respective vaccine efficacy rates were 50% and
49%. Women who received influenza vaccine were less
likely to develop influenza than those who received placebo (1.8% vs. 3.6%) as were their infants (1.9% vs.
3.6%). The results of this study indicate that influenza
vaccine is effective in preventing influenza in mothers
and their infants. Therefore, physicians should promote
the vaccine during pregnancy. (NEJM 2014; 371:918).
ASPIRIN REDUCES THE RISK OF
RECURRENT VENOUS
THROMBOEMBOLISM
Deep vein thrombosis (DVT) without apparent etiology is associated with a 10% risk of recurrence in the
first year and 5% risk each year thereafter. Treatment
of DVT usually consists of taking an oral anticoagulant
for 6 to 12 months. However, patients continue to be
at risk for recurrence. To assess whether aspirin could
be used as an alternative to oral anticoagulation for the
prevention of recurrent DVTs, researchers analyzed 2
studies that involved 1200
patients with venous thromboembolism (VTE) who
were given 100 mg of aspirin a day. During 2 years
of follow-up, treatment
with aspirin was associated
with 42% reduction in the
risk of VTE. The study
indicates that aspirin could be a promising and longterm alternative treatment for patients who are
stopping oral anticoagulant therapy or who are unable to undergo this treatment. (Circulation 2014).
SEVERE ORTHOSTATIC INTOLERANCE AND
SYNCOPE SECONDARY TO ACUTE
PANDYSAUTONOMIA NEUROPATHY
A 21-year-old female was admitted to the hospital for
recurrent syncope. The patient was completely healthy
until 4 weeks ago when she started to experience severe disabling orthostatic hypotension, lightheadedness
and syncope. She complained of dizziness that developed
soon after she rose from the supine position. She developed several syncopal episodes after attempting to stand
up. Her symptoms were so severe that she had to sit in
a chair with her knees pulled up close to her chest. The
patient also complained of dry mouth, decreased sweating and constipation. Tilt table test showed immediate
drop in blood pressure from 136/80 mmHg to 64/32
when the patient was placed in the tilt position without
change in her heart rate, and the patient became severely
pre-syncopal. Renal and liver function tests, CBC, ESR,
ANA, serologic testing for syphilis, abdominal CT, neuroconduction study, EMG and EEG were all normal.
The patient was diagnosed with acute pandysautonomia
neuropathy (PDAN ). This disease is characterized by
severe postganglionic sympathetic and parasympathetic
dysfunction with sparing of motor and sensory function.
This disorder may be autoimmune in nature and it could
be a variant of guillain barre syndrome. Ganglionic Acetylcholine Receptor (AChR) Autoantibody is the most
encountered antibody. Cancer is detected in a third of
patients with seropositivity. Therefore, a search for cancer is justified in patients with seropositive PDAN. This
patient was treated with Florinef and Midodrine and she
was instructed and trained to do maneuvers to help reduce the symptoms of orthostatic hypotension. Squatting
is an effective physical maneuver for increasing venous
return rapidly. This maneuver can be an emergency measure to prevent loss of consciousness when pre-syncopal
symptoms rapidly develop. Squatting can increase the
systolic blood pressure by 50 mmHg. Leg crossing is
also an effective maneuver to prevent lightheadedness
in the sitting position in patients with autonomic failure. Leg crossing can increase the systolic blood pressure by 20 mmHg. This patient improved significantly
and after several months she was able to stand still for
a few minutes. Spontaneous resolution of PDAN is
not infrequent. Partial recovery occurred after an average of 2.5 years and residual disability was not uncommon. In a case report a patient that was treated with
intravenous immunoglobulin obtained rapid recovery.
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Issue 25| November 2014
METFORMIN IMPROVES LONGEVITY
IN DIABETICS
FEMALE WITH SYNCOPE DUE TO
CONVERSION REACTION
It is estimated that diabetes shortens life expectancy by 8 years. Metformin
has been shown to have a
beneficial effect on cancer,
cardiovascular disease and
progression of prediabetes
to diabetes. Researchers
conducted a study to compare all-cause mortality in diabetic patients treated firstline with either sulfonylurea or Metformin monotherapy
with that in matched cohort without diabetes. The study
included 78,000 subjects treated with Metformin and
12,000 treated with sulfonylurea, along with 90,000
matched subjects without diabetes. There were 7400
deaths in total representing unadjusted mortality rate
14.4 per 1000 person-years for Metformin and 15.2 per
1000 person years for their matched controls. The unadjusted mortality rates for sulfonylurea and their matched
controls were 50 and 28 per 1000 person-years respectively. Therefore, patients treated with Metformin had a
small but statistically significant improvement in survival
compared with non-diabetics whereas those treated with
sulfonylurea had a reduced survival compared with nondiabetics. The findings indicate that Metformin may have
beneficial effects not only on patients with diabetes but
also for people without diabetes. Those treated with sulfonylurea had markedly reduced survival compared with
both matched and those receiving Metformin. The study
findings support the position of Metformin as first-line
therapy and imply that Metformin may confirm benefit in
non-diabetics. (Diabetes, obesity and metabolism 2014).
A 19-year-old female was referred for evaluation of recurrent syncope. She had 20 episodes of syncope over
the past 2 years. There were no triggers or warning
symptoms associated with syncope. Her previous work
up revealed no abnormalities. This included EKG, echocardiogram, 24-hour holter monitor, EEG, MRI, stress
test and EP study. Her physical examination, EKG and
laboratory values were all normal. The patient had a tilt
table test and at minute 15 she developed apparent loss of
consciousness. She suddenly closed her eyes and stopped
responding to verbal stimuli. This was associated with
stable blood pressure and heart rate. After 1 minute the
patient recovered suddenly after receiving a painful stimulus. Isuprel and sublingual nitroglycerrin testing were
negative. The patient was thought to have pseudosyncope secondary to conversion reaction. Therefore, she was
referred for psychiatric evaluation. Psychogenic pseudosyncope (PPS) is the appearance of transient loss of consciousness (LOC) in the absence of true LOC. PPS and
psychogenic pseudo seizure are common disorders but are
difficult to identify. Most cases of PPS are probably conversion reaction, which is hypothesized to represent the
physical manifestation of internal stressors. Conversion
implies that anxiety is converted into physical symptoms.
Conversion reaction is formerly known as hysteria. Conversion disorder presents with neurological symptoms including numbness, blindness, syncope, seizure or paralysis. The incidence of PPS is unknown, but it is likely to
be under-recognized and under-investigated. In the unexplained syncope population, patients are more likely to
be young females who frequently experience symptoms
prior to syncope including lightheadedness, shortness of
breath and tingling. The diagnosis is confirmed if during a
tilt table test, the patient develops apparent LOC without
any change in blood pressure or heart rate along with a negative EEG and possibly combined with vi eo. Conversion
reaction is assoc ated with disability and poor quality of
life.There is no treatment available for patients with PPS.
11
Issue 25| November 2014
ASYMPTOMATIC ATRIAL FIBRILLATION DETECTED DURING
SCREENING WITH EKG IS ASSOCIATED WITH
DOUBLING RISK OF STROKE
The incidence of atrial fibrillation is increasing. The first
manifestation of asymptomatic atrial fibrillation could
be stroke. Atrial fibrillation is responsible for 20-30%
of all strokes and 20-45% of individuals who have an
atrial fibrillation related stroke did not have prior diagnosis of atrial fibrillation. No recommendation is available for screening for asymptomatic atrial fibrillation
despite the risk of stroke. Researchers compared the
outcome of 5500 patients with asymptomatic atrial fibrillation that was detected on 12 lead EKG with that of
24,700 matched controls. Participants were followed for
3.5 years. The incidence of stroke was 19.4 events per
1000 person years in atrial fibrillation patients and 8.4
in the control. The incidence of all-cause mortality was
40 deaths per 1000 person-years among the atrial fibrillation patients vs. 21 in the control. Adjusted cumulative incidence of stroke at 18 months was just over 4%
among the untreated atrial fibrillation patients, and 1%
in patients treated with oral anticoagulation. All-cause
mortality was reduced from 7% to
4% and the risk of fatal and nonfatal MI reduced from 3% to 1.5%
at 18 months. The risk of stroke
was reduced to the same level as the
matched controls without atrial fibrillation. Treatment with aspirin provided no benefit. In this study, incidentally detected asymptomatic atrial fibrillation was 1.5% in persons above
65 years of age. This study also showed that treating
asymptomatic atrial fibrillation that is detected incidentally is associated with increased risk of stroke and MI.
Patients should be treated with anticoagulation. Screening on a wide scale can reduce the burden of atrial fibrillation and stroke. (Thrombosis and Hemostasis 2014).
WOMEN WITH LBBB AND SHORTER QRS (130-149 msec) BENEFIT
FROM CARDIAC RESYNCHRONIZATION THERAPY
FOR HEART FAILURE
Cardiac resynchronization
therapy (CRT) has dramatically improved symptoms
and prognosis in heart failure (HF). Recent guidelines
limit the class I indication
for CRT-ICD to patients
with systolic HF, LBBB and
QRS duration of 150 msec
or longer. Women were under-represented in CRT trials.
Therefore women with shorter QRS duration may benefit from CRT. To evaluate whether women with LBBB
benefit from CRT-ICD at shorter QRS durations than
men with LBBB do, FDA researchers analyzed combined
data from 3 randomized clinical trials. 4,000 participants
with systolic heart failure (80% mild) were randomized
to CRT plus ICD (CRT-D) or ICD alone. Among patients with LBBB, CRT-D was associated with a greater
reduction in the risk for HF events or death in women
than in men overall. This difference was seen mostly in
patients with LBBB and QRS duration of 130-149 msec.
In this group, absolute risk of HF or death was 23%
lower with CRT-D than with ICD in women compared
with a 4% (non-significant) lower absolute risk in men.
With QRS duration less than 130 msec, there was no
benefit for women or men from CRT-D over ICD. With
QRS duration > 150 msec, men and women benefited
significantly from CRT-D. The results of this study indicate that women with HF and QRS of 130-149 msec
benefit from CRT treatment. (JAMA intern med 2014).
12
Issue 25| November 2014
BETA BLOCKERS DO NOT IMPROVE PROGNOSIS IN PATIENTS WITH HEART
FAILURE IF THEY ALSO HAVE ATRIAL FIBRILLATION
Beta blocker
(BB) is the
mainstay
treatment to
improve prognosis in systolic
heart
failure. BB is
also used for
rate control in
patients with atrial fibrillation and heart failure. Researchers investigated the magnitude of beneficial effect of beta blocker on patients with both atrial fibrillation and heart failure. They conducted a meta analysis
of 10 randomized controlled trials that compared beta
blocker and placebo in systolic heart failure. The study
included 18,000 patients, 14000 of whom were in sinus rhythm and 3000 in atrial fibrillation. After a mean
follow-up of 15 years, 15% of patients in sinus rhythm
had died compared to 21% of those with atrial fibrillation. BBs were associated with a 27% reduction in
all-cause mortality among patients with sinus rhythm.
AMIODARONE-INDUCED PERIPHERAL
NEUROPATHY THAT WAS REVERSED
AFTER AMIODARONE
DISCONTINUATION
A 64-year-old man with a history of
paroxysmal atrial fibrillation that was
well controlled by Amiodarone 200
mg per day. On follow-up patient
complained of progressive weakness
of his legs and difficulty walking over the past 4 months.
The patient also complained of numbness of his legs and
hands. Physical exam showed muscle wasting of the lower
extremity, distal sensory and motor neuropathy with decreased reflexes. Nerve conduction study showed mixed
sensory and motor peripheral neuropathy. Amiodarone
was thought to be the culprit of the patient’s peripheral
neuropathy. Therefore, Amiodarone was discontinued.
On 3 month follow-up, patient reported significant improvement in his symptoms. He could walk normally
and his sensory symptoms completely disappeared. This
patient developed sensory motor neuropathy from treatment with Amiodarone. He developed the condition after
being on low dose Amiodarone for 2 years. His symptoms
resolved by discontinuance of Amiodarone. Although
Amiodarone-induced peripheral neuropathy is rare, physicians should have high index of suspicion when a patient
on Amiodarone develops similar symptoms to this patient.
However, no mortality reduction was seen for patients
with atrial fibrillation. The results of this study is disappointing but physicians will probably continue to
prescribe BB for rate control in patients with atrial fibrillation and heart failure, since other rate control medications such as calcium channel blockers and digoxin
might be associated with a worse outcome. This study
also indicates that we should always strive to keep patients with heart failure in sinus rhythm. (Lancet 2014).
DISCOVERY OF A BIOMARKER AND
SMALL MOLECULE TO TARGET
A MUTATION IN ALS
Amiotrophic lateral sclerosis (ALS) is
a progressive neurodegenerative disorder that affects both the upper and
lower motor neurons. The disease leads
to progressive loss of voluntary muscle
movement and eventually complete paralysis. The vast majority of patients die within 2 to 3 years but 5% survive 20
years. Frontofemoral dementia (FTD) is another neurodegenerative disease in which neurons in the frontal lobe
are destroyed. Both familial ALS and FTD are caused by a
mutation in a gene called C90RF72. This mutation results
in the production of a toxic protein called C9RAN which
accumulate in neurons and form inclusions. Researchers
found that this toxic C9RAN protein can be measured
in the spinal fluids of patients with ALS. This potential
biomarker in the CSF may provide a direct means to measure a patient’s response to treatment that blocks C9RAN
protein production. These researchers have developed for
the first time a small molecule drug candidate that can target the mutation with resultant inhibition of the C9RAN
protein. The compound dramatically decreased levels of
the toxic protein. The highest dosage reduced the toxic
protein by 50%. Further research
to refine and enhance the potency
of the compound might delay the
progression of ALS. Researchers are hoping to monitor the response of treatment by measuring
the level of the toxic protein in the
13
Issue 25| November 2014
BUERGER’S DISEASE IN HEAVY SMOKER WITH ACUTE
ARTERIAL CLOT OF LOWER EXTREMITY
A 55-year-old
man
heavy
smoker
for
many
years
was referred
for the evaluation of asymptomatic
PVCs. The
patient had normal left ventricular systolic function and,
he had no myocardial ischemia. His ventricular ectopies
were deemed benign and patient was offered no treatment for it. However, on further questioning, patient
had symptoms suggestive of buerger’s disease. Therefore,
I wanted to share this case with you. The patient reported that when he was in Egypt a few years ago, he
had acute arterial embolism of his left leg from which
he was treated successfully. Patient complained of progressive symptoms including leg pain on minimal walking and tingling of his feet, legs and hands. Patient had
several skin lesions on his lower extremities. Pthe continued to smoke until now. After suspecting Buerger’s
RECURRENT FALLS DUE TO
VASOVAGAL SYNCOPE
A 65-year-old female was admitted to the hospital with recurrent falls. Patient had a history of hypertension for which
she was treated with enalapril.
Patient had 5 episodes of falls
over the previous 2 months. She reported no warning
symptoms before the episodes and she did not remember
anything except finding herself on the floor. Her physical examination, EKG, echocardiogram and holter monitor were all normal. A tilt table test was done. At minute 6 of Isuprel test, her blood pressure dropped from
136/80 to 70/36 mmHg and heart rate decreased from
80 b/m to 40 b/m. A positive tilt table test suggests that
this patient’s falls are due to vasovagal syncope. 50% of
falls are actually secondary to syncope. Cardiovascular
syncope appears to be the main cause of unexplained
falls. Carotid sinus hypersensitivity, over the age
of 50, presents with unexplained falls. Falls also
can be caused by orthostatic hypotension or neurocardiogenic
syncope.
disease, patient was highly encouraged to stop smoking
immediately. Buerger’s disease or thromboangiitis obliterans is a rare form of vasculitis that is believed to be
an autoimmune reaction triggered by some component of
tobacco. The disease manifests with acute inflammation
and thrombosis of arteries and veins affecting the arms
and legs. The diminished blood flow may lead to critical
limb ischemia or claudication. The disease can present
also with rest pain and skin ulceration and gangrene of
the fingers and toes. The disease almost exclusively occurs in young heavy smokers. The disease should be differentiated from peripheral arterial disease (PAD) that is
caused by atherosclerosis, endocarditis and other types of
vasculitis, severe Raynaud’s phenomenon associated with
connective tissue disease and
clotting disorder. The only
known treatment for Buerger’s disease is complete cessation of smoking. Steroid and
oral anticoagulants have not
been proven to be effective.
SCREENING FOR MELANOMA BY
PRIMARY CARE PHYSICIAN LOWERS
SKIN CANCER MORTALITY
Guidelines in the United
States do not recommend
routine skin cancer screening by primary care physicians (PCP). Based on a
study published in JAAD
in 2012, a group of experts
in dermatology issued recommendations for screening for
melanoma by PCP. That one-year pilot study included
360,000 people who were examined by PCP trained to
identify skin cancer. Suspected lesions were evaluated
by dermatologists. Screening identified 34% more malignant skin tumors than would have been expected in
this population. After five years, melanoma death was
0.79 per 100,000 men vs. expected 2 per 100,000 and
0.66 vs. 1.30 expected per 100,000 women. This study
provides an evidence showing mortality benefits from
screening for skin cancer. The results should change the
current guidelines. Until guidelines are changed physicians should screen high risk population identified by
history and physical examination. Established risk factors include: family history of skin cancer and personal
history of excessive sun exposure or tanning bed usage,
excessive fair skin, many nevi, atypical or changing nevi,
high density of freckles. (JAMA Dermatology 2014).
14
Issue 25| November 2014
IN VIVO DETECTION OF CREUTZFIELDT
JAKOB DISEASE
Recently significant advances in the detection of
Creutzfieldt Jakob disease (CJD) in vivo were discovered. CJD is a fatal neurodegenerative disease with an
incident 1 per million per year that is characterized by
rapidly progressive dementia and myoclonus. It is caused
by an infectious agent called prion. It is a new biological
principle of infection. Actually, it is an abnormal version of a kind of protein. Normally these proteins are
harmless but when they are misshapen and folded they
become infectious and can destroy the normal biologic
processes. The defective protein can be transmitted by
contaminated harvested human brain products. Cannibalism (which is banned in African tribes) can transmit
prion leading to a disease known as kuru. A variant of
CJD has been linked to contaminated beef. 5 to 10% of
all CJD can acquire the disease genetically through a mutation of the gene that codes for the prion protein PRNP.
Prion is dangerous because it promotes refolding of native protein forming amyloids. This protein leads to progressive death of the brain cells resulting microscopically
in a sponge-like appearance hence the name transmissible
spongiform encephalopathy. Most victims die within six
months often from pneumonia due to impaired coughing reflexes. The diagnosis of CJD is made usually after
death. However, the presence of triphasia spikes on EEG,
14-33 proteins in the SCF, and high signal intensity in
the caudate nucleus and putamen bilaterally on MRI may
point to the diagnosis. Now in recent study researchers
found that prion protein (prpsc) can be detected in the
urine of patients with variant CJD (VCJD) using a protein misfolding amplification technique. The researchers
also found that prpsc was negative in the other two forms
of CJD namely sporadic CJD and the genetic CJD. Of
the 14 VCJD patient’s urine samples, 13 tested positive
for prpsc. Another research team tested olfactory epithelium samples from nasal brushing in 14 living patients
with sporadic CJD (SCJD). Real time quaking-induced
conversion (RT-Quick) testing had a sensitivity of 97%
and specificity of 100% in detecting SCJD. These two
tests represent significant advances in detecting variant
and sporadic CJD in vivo. (NEJM 2014; 371:5301).
EATING MORE FRUITS AND VEGETABLES IMPROVES SKIN COLOR TONE
AND INCREASES FACIAL ATTRACTIVENESS
Skin
coloration
plays an important role in facial
attractiveness. A
study published in
2012 showed that
eating more fruits
and vegetables can
change skin tone leading it to a healthier glow within
weeks. In the current study researchers asked a group of
participants to rate which face color they deemed most
attractive, those who used sunbathing or fake tanning to
achieve skin coloration vs. those who ate more fruits and
vegetables. Researchers found that just two extra portions of fruits and vegetables a day for six weeks was
enough to cause a detectable change in skin tone. The
yellowish coloration created by dietary carotenoids was
perceived as a healthy glow. 86% of participants rated
the high carotenoid version of faces as more attractive
than low carotenoid version and that skin coloration
in high carotenoid faces more attractive than the high
melanin faces (achieved by sunbathing,
sun beds or tanning lotions). The skin
color change from eating fruits and vegetables is attributed to carotenoids, an
organic pigment found in colored fruits
and vegetables such as carrots, apricots, oranges, mangos and spinach. 75%
of people do not eat enough fruits and
vegetables. The rapid achievement of a
healthy diet on attractiveness will be a
strong incentive for people to eat more
healthy foods. (The Quarterly Journal of experimental psychology 2014).
15
Issue 25| November 2014
COMBINATION OF VARENICLINE AND
NICOTINE REPLACEMENT THERAPY IS MORE EFFECTIVE THAN
VARENICLINE ALONE FOR SMOKING CESSATION
Nicotine from
cigarettes
stimulates the
release of dopamine which
triggers feelings of pleasure.
After
quitting smoking, the lack of nicotine leads to a reduction in dopamine release causing feelings of cravings
and withdrawal. Nicotine replacement and Varenicline
(Chantix) are useful for the treatment of smoking cessation. Varenicline acts as both nicotine antagonist and a
partial agonist. In another word, Varenicline is a partial
agonist, which means it blocks the nicotine receptors (reducing the addictive power of the drug) and stimulates
moderate release of dopamine to alleviate withdrawal
symptoms. No significant benefit was seen from combination of Varenicline and nicotine replacement therapy.
It was believed previously that the action of Varenicline
might neutralize nicotine effect. Researchers in the current study tested the efficacy of combining both drugs in
the success of quitting smoking. They randomized 446
smokers to 3 months of Varenicline titrated to 1 mg twice
a day plus nicotine replacement patches (15 mg worn for
16 hours daily) or to Varenicline plus placebo patches.
Abstinence at 4 weeks was 55% for combination therapy
vs. 40% for Varenicline only. At 24 weeks, abstinence
rates were 50% and 33% respectively. The results indicate that the combination of Varenicline and nicotine
replacement therapy is more effective than Varenicline
alone in smoking cessation. (JAMA 2014; 312:155).
PSA SCREENING DECREASED PROSTATE
CANCER RELATED MORTALITY BY 21%
FRACTIONAL FLOW RESERVE-GUIDED
PCI FOR STABLE CORONARY ARTERY
DISEASE IS SUPEROR TO OPTIMAL
MEDICAL THERAPY
Previous studies have shown conflicting results of PSA
screening regarding prostate cancer related mortality.
Because of that along with concern about the substantial harms that can result from over diagnosis, the US
Preventive Services Task Force recommended against
PC screening. Now 13 year follow-up data on the
PSA screening study was published. The trial included
160,000 men who were randomized to PSA screening
every 2-4 years or no screening. Participants underwent further evaluation if PSA level was more than
3 ng/mL. After 13 years of follow-up, PSA screening
was associated with a 21% improvement in prostate
cancer related mortality. The number needed to screen
and the numbers needed to treat to prevent one prostate cancer-related death were 780 men and 27 men respectively. The results confirm a significant reduction
in prostate cancer mortality from PSA screening. The
results of this long follow-up should not alter the current recommendation against screening. (Lancet 2014).
Optimal medical therapy (OMT) in stable coronary artery disease has
been shown to be as effective as percutaneous
coronary intervention
(PCI). In previous studies, PCI and stent placement were guided by subjective assessment of coronary
stenosis during coronary angiography. Fractional flow
reserve-guided PCI has been shown to be more accurate
in defining a significant coronary lesion that needs to be
stented. Researchers conducted a trial called FAME-2 to
compare FFR-guided PCI plus OMT with OMT alone.
The study included 1220 patients with stable CAD with
at least one stenosis with a FFR of 0.80 or less. Patients
were randomly assigned to undergo FFR-guided PCI plus
medical therapy or to receive medical therapy alone. After 2 years of follow-up the rate of death or myocardial
infarction was 44% lower in the PCI group than in the
medical therapy group 4.6 vs. 8%. The composite rate of
endpoint (death, MI or urgent revascularization) was 61%
lower in the PCI group than in the medical group 8% vs.
19%. The difference was driven entirely by a 77% relative reduction in urgent revascularization (4% and 16%
respectively). The results indicate that FFR-guided PCI
is superior to optimal medical therapy. (NEJM 2014).
16
Issue 25| November 2014
INCREASED BODY MASS INDEX RAISES THE RISK OF SEVERAL CANCERS
Epidemiologic studies have
shown that being overweight
(BMI 25-29.9 Kg/m2) or
obese (BMI > 30) increases
the risk of developing cancer.
Increased risk has been attributed to the excessive production of hormones and substances by fat cells including
estrogen, insulin and insulin-like grown factors (IGF-1),
Leptin and inflammatory factors. In the current study researchers have conducted a large study to assess the link
between body mass index (BMI) and specific cancer risk.
The study included 5.24 million people who were free of
cancer and who were followed for an average of 7.5 years.
166,955 participants developed 1 of 22 cancers during
follow up. Researchers found that BMI was linked to the
development of 17 cancers and the link was particularly
strong for 10 of these cancers. They found that every 5
kg/m2 increase in BMI was associated with a 62% higher
risk for uterine, 31% for gallbladder, 25% for kidney,
10% for cervical, 9% for thyroid and 9% for leukemia.
Higher BMI was also associated with a 19% higher risk
for liver cancer, 10% higher risk for colon, 9% higher
risk for ovarian and 5% higher risk for breast cancer.
Recent results from the NHANES survey showed that
68% of US adults age 20 years and older are overweight
or obese. A projection of obesity in 2030 estimated that
continuation of existing trends in obesity will lead to
about 500,000 additional cases of cancer in the US by
2030. This analysis also found that if every adult reduced their BMI by 1% (weight loss of 1 kg) for an adult
of average weight, this would prevent the increase in the
number of cancer cases and result in the avoidance of
about 100,000 new cases of cancer. (The Lancet, 2014).
ASPIRIN HALVES BREAST CANCER
RECURRENCE IN OVERWEIGHT WOMEN
work within the tumor. The results show that aspirin
benefits more with a disease driven by inflammation and
not just obesity. Limiting inflammatory signaling may be
an effective, less toxic approach to alternating the cancer promoting effects of obesity and improving patient’s
response to hormonal therapy. (Cancer research 2014).
Aspirin has been shown to have anti-cancer effects.
Researchers investigated the effect of aspirin on recurrence of breast cancer (BC). They examined data from
440 women diagnosed with invasive, estrogen receptor positive BC. In this study about 60% of the participants were overweight and 26% were obese. 80%
of the women took aspirin. The researchers found that
women with a body mass index of more than 30 had a
52% lower rate of BC recurrences and a 28-month delay in time to recurrence if they were regularly taking
aspirin or other NSAIDs. Researchers conducted a lab
experiment with cancer cells, fat cells and inflammation-promoting immune cells. The team observed that
factors associated with obesity promoted tumor growth
and resistance to therapy by initiating a signaling net-
17
Issue 25| November 2014
THROMBOLYSIS FOR ACUTE ISCHEMIC
STROKE SHOULD BE USED
RAPIDLY AND REGARDLESS
OF AGE OF INFARCT SIZE
ELECTIVE NON-CARDIAC SURGERY
SHOULD BE DELAYED IN PATIENTS
WITH STROKE FOR AT
LEAST 9 MONTHS
Thrombolysis is an effective treatment for ischemic
stroke when given quickly.
Such treatment is a race
against the clock, and every
minute counts. Researchers
conducted a meta analysis of
pooled data on 6700 patients with acute ischemic stroke
who were treated with thrombolysis. 25% of participants
were older than 80 years of age. Researchers showed that
patients with ischemic stroke were offered thrombolysis
too rarely or, if they were offered it, too slowly. Treatment within 3 hours with alteplase resulted in 75% higher good outcome when compared to receiving placebo.
For those given alteplase 3 to 4.5 hours after onset of
symptoms, there was 26% increased chance of a good
outcome. Those with a delay of more than 4.5 hours in
receiving treatment had a non-statistically significant
15% increase in the chance of good recovery. Irrespective
of age or stroke severity, treatment with alteplase within 4.5 hours of stroke onset significantly improves the
likelihood of a good outcome. Therefore, elderly should
be treated the same as young. In addition, both severe
and mild strokes should also be treated with thrombolysis. Reducing time to treatment requires team approach,
pre-hospital recognition of stroke, ED efficiency, rapid
simple imaging and use of telemedicine. (Lancet 2014).
Patients with recent stroke have a
higher risk for complications after noncardiac surgery (NCS). However for
how long stroke patients have to wait
to have elective surgery after stroke
is unknown. Researchers investigated
the best timing to perform elective
surgery in patients with recent stroke.
They analyzed data on half a million
people who underwent elective NCS.
7500 patients had a history of stroke (TIA and hemorrhagic strokes were excluded). Those who had strokes
had a higher risk of major adverse cardiovascular events
(myocardial infarction, ischemic stroke, cardiovascular
related death). The risk was dependent on the time between stroke and NCS. The odds ratio was 14.0 if stroke
was within 3 months before surgery, 5.0 if stroke was 3-6
months before surgery, 3.0 if stroke was 6-12 months
before surgery and 2.5 if stroke occurred 12 months
or more before surgery.
The risk leveled off at
9 months. The results
of this study indicate
that physicians should
wait at least 9 months
before scheduling stroke
patients for elective
non-cardiac
surgery.
CARDIOVERSION IS SAFE IN PATIENTS WITH ATRIAL FIBRILLATION
TREATED WITH RIVAROXABAN
Current guidelines
recommend at least
3 weeks of anticoagulation
before electrical cardioversion, followed by at least 4 weeks of anticoagulation
after the procedure. Little data exists on the safety of
cardioversion in patients taking one of the novel oral
anticoagulants. Researchers conducted a study to compare the outcome of cardioversion in atrial fibrillation
patients who are taking rivaroxaban vs. warfarin. The
study included 1500 patients who were assigned to rivaroxaban 20 mg or to warfarin. Patients were assigned to
early (1-5 days) vs. delayed (3-8 weeks) cardioversion
strategy. The primary efficacy outcome (PEO) was the
composite of stroke, TIA, peripheral embolism, myocardial infarction and cardiovascular death. The PEO occurred in 0.5% in the rivaroxaban group and in 1.0%
in the warfarin group. In the rivaroxaban group the rate
of PEO was 0.7% following early cardioversion and
0.24% following delayed cardioversion. In the warfarin
group, 1.0% had PEO following early cardioversion and
0.93% following delayed cardioversion. Major bleeding
occurred in 0.6% in the rivaroxaban group and 0.8 in
the warfarin group. It is important to note that the rate
of stroke in the non-anticoagulated patients who underwent cardioversion was 5% to 7%. This study indicates
that rivaroxaban is effective and safe in patients who undergo electrical cardioversions. (ESE Congress 2014).
18
Issue 25| November 2014
SELF-MONITORING AND MANAGEMENT OF HYPERTENSION IS MORE
EFFECTIVE THAN USUAL CARE
Hypertension (HTN) is defined as blood pressure (BP) >
140/90 mmHg, normal BP < 120/80 and pre-hypertension is between 121/81 and 139/89 mmHg. Self monitoring and medication self titration may be more effective
than usual care but it is not done commonly in the US.
Researchers conducted a study to compare self-management of HTN with usual care. 450 high risk patients
were randomized to self monitoring and self management
protocol or to usual care. Self management patients were
trained to take their BP daily and were instructed to adjust their medications according to their BP readings and
instructions in the plan. Usual care patients relied on
their doctors to take periodic readings and to make medication changes. Mean BP at baseline was 143/80 mmHg
and target BP was 120/70. At 1 year, the BP of self management patients was significantly lower than the usual
VITAMIN D DEFICIENCY INCREASES
THE RISK FOR DEMENTIA AND
ALZHEIMER’S DISEASE
To determine whether
low vitamin D levels are
associated with dementia
and Alzheimer’s disease,
a study was conducted
to assess this association.
The study included 1700
older adults without dementia, stroke and cardiovascular disease (CVD) who
underwent serum vitamin D level measurement and
they were followed for six years. During that period,
170 participants developed dementia and 100 developed
Alzheimer’s disease. Compared with participants with
baseline vitamin D level of 50 nmol/L or higher, those
with a level of 25-50 had 50% higher risk for dementia and 70% higher risk for Alzheimer’s disease. The
risk was increased dramatically in those with severely
deficient vitamin D levels. Those who had serum vitamin D level of < 25 had an odds ratio of 2.25 and
those who had a deficient level of 25-50 had an odds
ratio of 1.53 for dementia or Alzheimer’s disease. The
results indicate that vitamin D deficiency is associated
with an increased risk for dementia and Alzheimer’s
disease. People should be screened for vitamin D and
people with low vitamin D level should be advised to
take vitamin D supplementation. (Neurology 2014).
care patients 128/73 vs. 138/76 mmHg, a difference of
10 mmHg in systolic and 3 for diastolic. Therefore, this
study indicates that even people at significant risk for
cardiovascular disease and stroke can take an active role
in reducing their BP by self measurement and self adjustment of their medications. (JAMA 2014, 312:799).
ORAL USE OF BISPHOSPHONATE
INCREASES THE RISK FOR
OSTEONECROSIS OF THE JAW
Osteonecrosis of the jaw (ONJ)
is a severe bone disease that presents initially as a lesion in the
gingiva that does not heal. The
lesion may be asymptomatic for
weeks and months until the lesion with exposed bone appears.
ONJ was reported initially after
high dose intravenous bisphosphonate treatment for malignant conditions. The condition was observed spontaneously or after invasive dental
work. However, the possible risk from lower oral doses
of bisphosphonate taken to prevent or treat osteoporosis
remains uncertain. Researchers conducted a study to investigate the association between ONJ and oral alendronate or raloxifene for osteoporosis. Among 7332 patients
who were taking oral alendronate, 40 (0.55%) were diagnosed with ONJ, an average of four years after initiation of alendronate. In a control group of 1882 patients
who were treated for osteoporosis with raloxifene, only
one patient developed ONJ. This represents an incidence
of ONJ that is seven-fold higher with alendronate than
with raloxifene. Risk factors for developing ONJ among
users of alendronate include diabetes, rheumatoid arthritis, older age
and alendronate use for more than
3 years. Treatment of severe cases
of ONJ requires surgical removal
of the affected bone. Atypical femur fracture after long-term use of
bisphosphonate was also described.
(J Clin Endo Metab 2014; 99:2729).
19
Issue 25| November 2014
MAJORITY OF ELIGIBLE PATIENTS DO NOT RECEIVE ASPIRIN FOR PRIMARY
PREVENTION OF MYOCARDIAL INFARCTION AND STROKE
Primary prevention trials
showed that aspirin use for
primary prevention reduced
the risk of myocardial infarction (MI) by 32% in men and
the risk of stroke by 17% in
women. Therefore, the US Preventive Services Task
Force recommends aspirin for men ages 45-79 years to
reduce the risk of MI and for women ages 55-79 years to
reduce the risk of ischemic stroke. However, aspirin remains underused in the primary prevention settings. Researchers examined physician records for aspirin use in
individuals 40 years of age and older to see the adherence
to guidelines. Using the 2011-2012 NHANES data, it
was estimated that among 3000 participants, 87% of men
and 16% of women were eligible for aspirin use based on
the Framingham risk equation. Just 34% of eligible men
recalled recommendations to take low dose aspirin each
day to prevent MI, stroke or cancer. Just over 40% of
eligible women recalled receiving such recommendation.
In 470 patients with actual cardiovascular disease, 76%
FDA APPROVED AN
INHALED INSULIN
The FDA has approved Afrezza, an inhaled human insulin
product for the treatment of
patients with type 1 and type
2 diabetes who require mealtime insulin. Inhaled insulin
could be a good option for people who do not like needles. The drug is taken before each meal. The inhaled
powder is absorbed rapidly from the cells in the lungs.
It peaks in the blood in 15-20 minutes, while injected
insulin takes about an hour to peak. The inhaled insulin
is also cleared more quickly than injected insulin. The
FDA approval of Afrezza was based on 3000 patients
with diabetes. At 24 weeks, the drug reduced HbA1c
level by 0.4% in both type 1 and type 2 diabetes. Afrezza
and injected insulin-controlled blood sugar equally well
in a 24 week study. In another study Afrezza resulted
in better control of blood sugar in patients with type 2
diabetes who were not controlled on oral medications.
Inhaled insulin can lead to cough and throat pain or irritation and bronchospasm. It is not recommended for
patients who smoke or who have COPD. Afrezza will
not replace the need for injected long-acting insulin
for those who need it. (ADA scientific session 2014).
recall their physicians recommending they take aspirin to
prevent MI or stroke. The benefit from aspirin depends
on the presence of risk factors in men such as age, diabetes, high cholesterol, low HDL, hypertension, smoking
and sedentary lifestyle.
Stroke risk factors for
women include age,
atrial fibrillation, coronary artery disease,
hypertension, left ventricular hypertrophy,
smoking and diabetes.
(J of gen int med 2014).
NSAID AND ANTIPLATELET AGENTS
INCREASE THE RISK FOR
LOWER GI BLEED
The risk for upper gastrointestinal
(GI) bleed increases
by taking NSAID
and
antiplatelet
agents. The association of these drugs
and lower GI bleed
is not well known. In a retrospective study, researchers analyzed drug use and clinical data from 320 patients
with lower GI bleed confirmed by colonoscopy and they
compared it to 3300 individuals who received colonoscopy but without bleeding. NSAIDs were associated
with lower GI bleed with adjusted odds ratio (AOR) of
2.3 for nonselective and 2.8 for COX-2 inhibitors. Antiplatelet drugs alone were not significantLY associated
with lower GI bleed. NSAID plus antiplatelets were associated with low GI bleed with AOR of 4.5. Low dose
aspirin with thienopyridine or other antiplatelet were
associated with lower GI bleed with AOR 2.2 and 3.6
respectively. Use of 2 different NSAIDs was associated
with AOR of 4.9 while use of a single NSAID was associated with an AOR of 2.3 for lower GI bleed. The
effect of combined antithrombotic drug regimen on lower GI bleed remains unknown. (Gastro Endosc 2014).
20
Issue 25| November 2014
TICK BITE CAN TRIGGER SEVERE ALLERGIC REACTION AFTER
RED MEAT INGESTION
A new bizarre illness of red meat allergic reaction after
a lone star tick bite was described. This tick originated
in Texas and was named for the yellow spot on its back.
The tick has sugar (the culprit) that human bodies do
not have (galactose-alpha-1, 3 galectose) or alpha-gal.
This sugar is also naturally found in red meat. The sugar
is fine when ingested through foods but a tick bite may
trigger an immune response. When a person with a tick
bite eats red meat the body sees the sugar as a foreign
substance and releases antibodies to attack it. The illness
is characterized by delayed reaction of urticaria or anaphylaxis appearing 4 to 8 hours after consumption of red
meat. This condition was first described in 2011 and has
been spreading from the southwest and the east to more
parts of the US. It is unknown if the allergy is permanent.
The lone star tick is
most common in wooded areas, particularly in
forests with thick underbrush and large trees.
Doctors should recognize
this condition. A blood test can confirm the meat allergy.
MUTATION IN PALB2 GENE INCREASES THE RISK OF BREAST CANCER AS
MUCH AS BRCA MUTATIONS
Mutations in BRCA genes greatly raise the risk for breast
cancer (BC). It is estimated that 5-10% of BC is caused
by BRCA mutations. Now scientists identified a new
gene PALB2 mutation that increases the risk of BC. This
gene encodes for a protein that works similar to BRCA in
DNA repair and as a tumor suppressor. Cancer can flourish when these genes are mutated. Researchers examined
BC risk among 360 members of 154 families in which at
least one person had BC and a loss of function mutation
in PALB2 (but no BRCA mutations). They found that
BC risk was 9 times higher among mutation carriers than
in the general population, similar to the risk of BRCA
gene mutations. The absolute BC risk by age 70 among
women with PALB2 mutation was 35% and 60% among
women with 2 or more close relatives with BC. This
mutation also increases the risk in men. This high risk
from PALB2 mutation will justify adding it to genetic
testing along with BRCA1 and BRCA2. (NEJM 2014).
21
Issue 25| November 2014
SEEDING OF HIV RESERVIOR
OCCURS EARLY IN THE FIRST
FEW DAYS OF INFECTION
The most critical factor for curing HIV infection is the
presence of viral reservoir in which the virus can stay
dormant in the cells for many years and avoid elimination by antiretroviral drugs. The early seeding of the
virus represents a challenge to HIV eradication according to a new study. The study looked at when the viral
reservoir is established during HIV infection and the effects of antiretroviral therapy (ART) on the reservoir.
In this study, researchers initiated suppressive ART in
a group of monkeys on day 3, 7, 10 and 14 after intrarectal SIV infection. They found that the reservoir
was established in tissues during the first few days of
infection before the virus was ever detected in the blood.
Animals treated on day 3 following infection showed
no evidence of virus in the blood and did not generate
any SIV-specific immune responses. However, after 6
months of ART, all the animals in the study exhibited
viral resurgence when treatment was stopped. The publication of this study coincided with a report of HIV resurgence in a baby who was believed to have been cured
by early administration of ART. The data suggests that
extremely early initiation, extended ART duration, and
probably additional intervention to target viral reservoir
will be required for HIV eradication. (Nature, 2014).
NOVEL MENINGOCOCCAL VACCINE TO
DECREASE BACTERIAL CARRIAGE AND
PERSON TO PERSON TRANSMISSION
The aim of vaccination is to induce antibodies in the blood
to prevent diseases. Two novel vaccines were introduced
for the aim of preventing the transmission of meningitis
bacteria from person to person by decreasing bacterial
carriage in the throat and nose. Scientists produced the
vaccines by analyzing the genetic structure of thousands
of B strains, looking for shared features which could be
targeted. Meningococcal bacteria are common and are
carried harmlessly in the nose or throat by about 10%
of people. Bacteria are passed on through close contact.
Babies and young children are most vulnerable for meningitis. Researchers tested the effect of the quadrivalent
meningococcal ACWY-CRM and 4CMenB on meningococcal carriage in a phase 3 randomized trial. Participants
who were 18 to 24 years old were either given two doses
of a control vaccine, two doses of the 4CMenB vaccine or
one dose of MEN ACWY-CRM and then a placebo. The
results showed that MEN ACWY-CRM reduced carriage
rate by 39% while 4CMenB vaccine reduced carriage rate
between 20 % and 30%. This discovery may change the
way new vaccines are made in the future. (Lancet 2014).
22
Issue 25| November 2014
PROPHYLAXIS WITH PALIVIZUMAB FOR THE PREVENTION OF
RSV IN PREMATURE INFANTS
Premature infants are uniquely vulnerable to infection with respiratory syncytial virus (RSV). The degree of prematurity is associated with increased risk of
broncholitis-associated death. Palivizumab (Synagis)
is a monoclonal antibody that is used prophylactically as passive immunization for the prevention of RSV
infection in high risk infants. A new guideline limits prophylaxis treatment with synagis to infants born
before 29 weeks gestation and pre-term infants born
less than 32 weeks of gestation with chronic lung disease (CLD) and those with significant congenital heart
disease. Synagis prophylaxis is recommended during the second year only for premature infants with
CLD who require continued medical support for CLD.
DAILY ASPIRIN USE REDUCES CANCER RISK
and 7% in women. 9% reduction does not seem to be
impressive, but along with other simple measures such
as stopping alcohol consumption, avoiding red meat and
animal fat, reducing weight and performing exercise can
have significant effects. (Annals of oncology 2014).
Recent review showed that low-dose daily aspirin (75325 mg) initiated at 50 to 65 years of age reduced cancer incidence and mortality. There was relation between
the length of aspirin use and the degree of benefit. Taking aspirin for 10 years reduced the risk by 9% in men
23
Issue 25| November 2014
KIDNEY STONES ARE ASSOCIATED WITH INCREASED RISK
OF CORONARY HEART DISEASE
are associated with increased risk of coronary artery disease (CAD). Researchers found that patients with kidney stones were 15% more likely to experience a CHD
incident, myocardial infarction or coronary artery bypass
grafting compared with patients who did not have kidney
stones. The association between kidney stones and CHD
suggests that a thorough cardiovascular assessment should
be considered in patients who develop kidney stones. Patients with kidney stones should adapt lifestyle modifications that could reduce the risk of both kidney stones and
CV problems, such as weight loss, a healthy diet, smoking cessation and exercise. (Am J kidney diseases 2014).
The incident of kidney stones has been increasing over
the past 3 decades. Ten percent of people will have a
kidney stone at some point in their lives. Kidney stones
increase the risk of developing coronary heart disease
(CHD). The current study indicates that kidney stones
DRAMATIC IMPROVEMENT IN CARDIOVASCULAR
OUTCOMES IN THE PAST DECADE
and treatment of hypertension and hyperlipidemia, decline in smoking and other factors. Researchers examined the acute CVD outcome during the past decade.
They reviewed data on 30 million Medicare beneficiaries. They found that hospitalization rates have declined
for unstable angina (UA), myocardial infarction (MI),
heart failure (HF), and ischemic stroke (IS). MI hospitalization dropped 4.6% annually from 1999 through
2011. The adjusted rate of 30 day mortality during that
period declined 21% for MI, 13% FOR UA, 16% for
HF and 5% for IS. Similar declines were observed for 1
year mortality. Additional efforts are necessary to further the reduction in CVD burden. (Circulation 2014).
We have witnessed dramatic improvement in cardiovascular disease (CVD). The improvement was a reflection of advances in the identification of risk factors
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