• Some Cases of Primary Unexplained Infertility Might Have a Viral Cause
• Statins in Patients with Coronary Disease Who Are Older than 80
• One Hour of Exercise Daily Can Offset Mortality Risk of Sitting at Work All Day
• Bariatric Surgery Linked to Higher Fracture Risks and Changed Fracture Patterns
• Integrity of Breast Milk Is Maintained After Freezing for 9 Months
• Hope and Hype over Stem Cell Treatments for ALS
• How Reliable Is Mammographic Assessment of Breast Density?
• CDC: Kratom an "Emerging Public Health Threat" in U.S.
• A Quarter of U.S. Adults Have at Least Two Chronic Conditions
MM: There have been numerous examples of Low Dose Naltrexone (LDN) showing benefit for infertility but the mechanism of success has been largely unknown. This article and its association of viral infection and infertility may be one of the conditions that LDN has assisted reproduction while being sort of "under the radar". It may also explain why other natural approaches seem to complement treatments for fertility such as probiotics and higher doses of vitamin D3.
PLoS One 2016 Jul 1; 11:e0158304
Some Cases of Primary Unexplained Infertility Might Have a Viral Cause
Half of women with primary infertility — but no controls — harbored herpesvirus-6A in endometrial cells.
Viral infections have long been suspected to be a cause of primary unexplained infertility, but no viruses have been implicated. Italian investigators studied 30 women with unexplained primary infertility and a control group of 36 age-matched women with at least one successful pregnancy.
Half of women with primary infertility — but no controls — harbored human herpesvirus (HHV)-6A in endometrial cells. In contrast, no HHV-6B (a different herpesvirus) was found in any endometrial samples. Moreover, the concentration of HHV-6A was substantial, and HHV-6A proteins also were detected by immunohistochemistry. Striking differences between groups were seen in the endometrial “immune milieu”: Different types of natural killer lymphocytes were found, as well as different immune mediators (cytokines) in uterine flushing samples. Finally, infertile women had higher levels of circulating estradiol than did controls.
COMMENT: This study shows endometrial infections with a particular virus, HHV-6A, in nearly half of women with unexplained infertility. Many people are permanently infected with this virus during childhood or early adulthood. The study also shows some striking differences between infertile and fertile women in their endometrial immune milieu. Whether the viral infection is the cause or an effect of the immune changes is unclear. Nevertheless, because some antivirals successfully eradicate HHV-6A, we might have a new approach to treating some women with primary unexplained infertility.
CITATION(S): Marci R et al. Presence of HHV-6A in endometrial epithelial cells from women with primary unexplained infertility. PLoS One 2016 Jul 1; 11:e0158304.
(http://dx.doi.org/10.1371/journal.pone.0158304)
http://www.ncbi.nlm.nih.gov/pubmed/27367597?access_num=27367597&link_
type=MED&dopt=Abstract
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J Am Geriatr Soc 2016 Jul; 64:1475
Statins in Patients with Coronary Disease Who Are Older than 80
In an observational study, statins were not associated with significantly lower mortality.
For people in their 80s and 90s who have no history of cardiovascular disease, using statins for primary prevention is unlikely to confer substantial benefit. But what about prescribing statins for patients in this age group who have known coronary disease?
In this single-center study from Washington University in St. Louis, researchers conducted a retrospective analysis of 1262 older patients (age, ≥80; median age, 85) who were discharged alive after hospitalizations for acute myocardial infarction, unstable angina, or chronic coronary disease; 72% were discharged on statins, and 28% were not. In two types of analyses with propensity-score adjustments for baseline differences between statin recipients and non-recipients, a small but statistically nonsignificant mortality difference was found between the statin and nonstatin groups during median follow-up of 3 years (hazard ratio, ≈0.90).
COMMENT: On one hand, a larger study might have shown the above-noted 10% relative mortality difference to be significant, and nonfatal outcomes that could favorably affect quality of life were not reported in this study. On the other hand, we have no information on statin side effects among these patients. In the absence of randomized trials of statin therapy for secondary prevention in patients who are older than 80, observational data, clinical intuition, and patient preferences will have to guide clinical decision making.
CITATION(S): Rothschild DP et al. Effect of statin therapy on mortality in older adults hospitalized with coronary artery disease: A propensity-adjusted analysis. J Am Geriatr Soc 2016 Jul; 64:1475.
(http://dx.doi.org/10.1111/jgs.14207)
http://www.ncbi.nlm.nih.gov/pubmed/27295083?access_num=
27295083&link_type=MED&dopt=Abstract
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One Hour of Exercise Daily Can Offset Mortality Risk of Sitting at Work All Day
By Amy Orciari Herman, Edited by Susan Sadoughi, MD
Engaging in about an hour of brisk walking or other moderate-intensity activity each day can negate the increased mortality risk associated with sitting for prolonged periods, suggests a meta-analysis in Lancet's physical activity series.
The analysis comprised 16 prospective cohort studies that reported on adult sitting or TV viewing time, physical activity, and mortality; over one million men and women were included. Among the least active participants (those engaging in about 5 minutes of moderate activity daily), sitting more than 8 hours daily was associated with a 27% increased mortality risk compared with sitting fewer than 4 hours daily. Prolonged sitting was also associated with increased mortality, albeit to a lesser extent, among more active individuals. However, among the most active individuals — those getting 60–75 minutes of activity daily — prolonged sitting was no longer associated with mortality.
In addition, watching TV for more than 3 hours daily was associated with increased mortality in all but the most active group. The most active participants had to watch TV for 5 hours a day to see a mortality increase.
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Bariatric Surgery Linked to Higher Fracture Risks and
Changed Fracture Patterns
By Joe Elia, Edited by Susan Sadoughi, MD
Bariatric surgery for severe obesity is associated with higher risks for bone fracture as well as a changed pattern in fracture sites, a study in The BMJ finds. Fractures before surgery were typically believed to be obesity-related (i.e., distal lower limb), while those after surgery followed an osteoporotic pattern (i.e., upper limb, clinical spine, pelvis, hip, and femur).
Canadian researchers used provincial medical records to study some 13,000 severely obese patients who had undergone bariatric surgery. Patients' rates of fracture — both before and after surgery — were compared with rates among 38,000 obese and 127,000 nonobese controls who had not undergone surgery.
Before surgery, the bariatric group had experienced more fractures (10.5% prevalence) than the obese (8.1%) or nonobese (6.6%) controls. After surgery, the differences persisted during a mean follow-up of 4.4 years, although fracture site patterns changed in the surgery group.
http://www.bmj.com/content/354/bmj.i3794
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J Pediatr 2016 Jul13
Integrity of Breast Milk Is Maintained After Freezing for 9 Months
Freezing freshly expressed or briefly refrigerated breast milk for 9 months maintains macronutrients but reduces pH.
Freezing expressed breast milk is a means of providing nourishment when maternal contact isn't possible (e.g., when neonates are hospitalized.) Various protocols have been recommended for freezing, although the optimal duration is unclear. These investigators obtained 100 mL of freshly expressed breast milk from each of 40 mothers (mean age, 32 years, 61 days postpartum) and divided each sample into 9 aliquots: 4 were frozen at −20°C and 4 were refrigerated for 72 hours and subsequently frozen at −20°C. Aliquots were stored for 1, 3, 6, or 9 months, and were then placed at −80°C until they were analyzed simultaneously. One aliquot was stored directly at −80°C at baseline.
The study was supported by a maker of breast-feeding products.
Total bacterial colony counts declined over time — more rapidly in the pre-refrigerated samples — and were minimal by 3 to 6 months. Gram positive bacteria declined more rapidly than gram negative bacteria. Mean pH declined over time to a mean of 6.3 at 9 months. Nonesterified fatty acid concentration increased over time. Total protein, lactoferrin, secretory IgA, and osmolality did not change over time.
COMMENT: The integrity of breast milk appears to be maintained during 9 months of freezing at −20°C, and is not affected by pre-refrigerating for 48 hours. Current freezing protocols appear to be safe and appropriate. The authors raise the interesting question of whether the loss of bacteria with freezing might alter the development of the child's microbiome. This is a great topic for future study. Still, breast milk is best.
CITATION(S): Ahrabi AF et al. Effects of extended freezer storage on the integrity of human milk. J Pediatr 2016 Jul13; [e-pub].
(http://dx.doi.org/10.1016/j.jpeds.2016.06.024)
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Neurology 2016 Jun 29
Hope and Hype over Stem Cell Treatments for ALS
An interim report of data from an ongoing open-label trial supports the safety of intraspinal cord injection of stem cells but suggests that dose-limiting toxicity may have been reached.
Intra–spinal cord injection of neural stem cells derived from human spinal cord is one of many stem cell–based approaches being investigated to treat amyotrophic lateral sclerosis (ALS). Researchers now report 9-month safety data from an ongoing, partially manufacturer-funded (Neuralstem, Inc.) phase II study (n=15), along with data from a previously reported phase I study (n=9). Participants received one of three escalating doses (cells/injection) and numbers of injections in the cervical and lumbar spinal cord.
Most participants had uneventful surgical and postoperative courses. Two of the six patients in the highest dosing group (20 injections of 800,000 cells/injection, spread across both sides of the lumbar and cervical cord) had severe complications from the treatment: One had postoperative spinal-cord swelling with pain, sensory loss, and paraparesis. The other had severe delayed-onset neuropathic pain in the extremities. Overall, disease trajectories did not differ from those of three historically derived control groups.
COMMENT: This is the fifth publication describing the Neuralstem phase I trials, phase II trials, or both (Stem Cells 2012; 30:1144, Neurosurgery 2012; 71:405, Neurosurgery 2014; 74:77, and Ann Neurol 2014; 75:363). Although safety thresholds were not defined a priori, occurrence of spinal cord complications in two of six patients in the highest dosing group suggests that dose-limiting toxicity may have been reached. This publication provides encouraging safety data but raises many questions. Why were results from a previously completed and reported phase I study included? How should readers reconcile discrepancies among the five publications in the clinical characteristics (e.g., disease duration at the time of stem cell transplantation) of the same patients? How did this trial, billed as a phase Ib study (NIH Project Reporter number 5R01NS077982-04,https://projectreporter.nih.gov), become a phase II study? Why are the results of predefined secondary endpoints not reported? Of particular concern are the multiple overlapping publications of the same small cohort of patients, each time reporting incomplete data from ongoing trials, making it especially difficult for the reader to acquire a clear view of this therapeutic approach. Clarity is critical given the hype that already surrounds stem cell therapies.
CITATION(S): Glass JD et al. Transplantation of spinal cord–derived neural stem cells for ALS: Analysis of phase 1 and 2 trials. Neurology 2016 Jun 29; [e-pub]. (http://dx.doi.org/10.1212/WNL.0000000000002889); Appel SH and Armon C.Stem cells in amyotrophic lateral sclerosis: Ready for prime time? Neurology2016 Jun 29; [e-pub].
(http://dx.doi.org/10.1212/WNL.0000000000002906)
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MM: It would seem from this article that density assessments vary widely from radiologist reading to radiologist and even appear to get multiple interpretations by the same doctor looking at the same mammogram. We need to be vigilant and to have testing available. However, at this time we do not seem to have a better method, to date, that is accepted and is both cost effective and accurate. It appears that the human factor in reading mammograms is not optimally effective. That should mean that we need a better tool for assessment. One problem is that this equipment is expensive and that there may be resistance from hospitals and clinicians who have purchased the expensive equipment. That is a shame.
Ann Intern Med 2016 Jul 18
How Reliable Is Mammographic Assessment of Breast Density?
Observational analysis of large data set finds wide variation in density assessment by radiologists.
Having mammographically dense breasts impedes performance of screening mammography and has been associated with excess risk for breast cancer. Radiological categories of breast density are: almost entirely fat, scattered fibroglandular densities, heterogeneously dense, or extremely dense (the first two categories defined as “nondense” and the latter two as “dense”). Many states have mandated that information on breast density be communicated to women, focusing attention on supplemental breast imaging. Investigators analyzed prospectively collected observational data from screening mammograms performed between 2011 and 2013 (145,123 women, 216,783 screens; mean age, 58; 80% non-Hispanic white) from 30 U.S. radiology centers (83 radiologists). Data on consecutive screens were available for 45,313 women.
Overall, 37% of mammograms were assessed as dense. Radiologists varied substantially in assigning the four breast density categories. Based on the “dense versus nondense” classification, 25% of radiologists rated <29% of mammograms as dense, while 25% indicated ≥51% were dense. The least variation among ratings occurred for the “extremely dense” category. Among women with consecutive mammograms read by different radiologists, differing density categories between readings were noted in 33%. When stratified as dense versus nondense, consecutive readings were discordant 17% of the time for different radiologists and 10% of the time for the same radiologist.
COMMENT: The substantial variation among radiologists regarding breast density assessment supports previous guidance from the American College of Obstetricians and Gynecologists and others that a screening mammography report of dense breasts should not routinely trigger a recommendation for supplemental breast imaging (NEJM JW Womens Health May 2014 and Obstet Gynecol 2014; 123:910; NEJM JW Womens Health Jun 2015 and Ann Intern Med 2015 May 18; [e-pub]). However, when radiologists report extremely dense breast tissue, clinicians may consider recommending that the subsequent screen include concomitant breast tomosynthesis (NEJM JW Womens Health Jun 2016 and JAMA 2016 Apr 26; [e-pub]).
CITATION(S): Sprague BL et al. Variation in mammographic breast density assessments among radiologists in clinical practice: Findings from a multicenter observational study. Ann Intern Med 2016 Jul 18; [e-pub].
(http://dx.doi.org/10.7326/M15-2934)
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CDC: Kratom an "Emerging Public Health Threat" in U.S.
By Amy Orciari Herman, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
Calls to U.S. poison centers for exposures to the botanical kratom rose 10-fold between 2010 and 2015, according to a report in MMWR. Kratom (Mitragyna speciosa) is used as a stimulant and an opioid substitute.
Overall, there were 660 kratom-associated calls. Roughly three-quarters of exposures were intentional, and 90% were through ingestion. Medical outcomes were considered minor in 25%, moderate (requiring treatment but having no residual disability) in 42%, and major (life-threatening with residual disability) in 7%. There was one death, in a person also exposed to paroxetine and lamotrigine. Outcomes were not reported for the remainder of the cases.
The most common symptoms of exposure included tachycardia, agitation/irritability, drowsiness, nausea, and hypertension.
"Kratom use appears to be ... an emerging public health threat," the authors write. "Health care providers should be aware that the use of kratom can lead to severe adverse effects, especially when consumed in combination with alcohol or other drugs."
http://www.cdc.gov/mmwr/volumes/65/wr/mm6529a4.htm
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A Quarter of U.S. Adults Have at Least Two Chronic Conditions
By Amy Orciari Herman, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
Roughly one-fourth of U.S. adults are living with two or more chronic conditions, according to an MMWR article.
CDC researchers used data from the 2014 National Health Interview Survey to estimate the proportion of adults in each state with two or more chronic conditions. The conditions in question were arthritis, asthma, cancer, chronic obstructive pulmonary disease, coronary heart disease, diabetes, hepatitis, hypertension, stroke, and renal weakness or failure.
Overall, women were more affected than men (27% vs. 24%). By age group, the prevalence ranged from 7% among those aged 18–44 to 62% among those aged 65 and older. The prevalence was highest in Kentucky, at 38%, and lowest in Colorado, at 19%. See how your state measures up at the link below
http://www.cdc.gov/mmwr/volumes/65/wr/mm6529a3.htm
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