geoffrey modest medical blogs

The International Agency for Research on Cancer (IARC) working group just assessed the relationship between overweight/obesity and cancers, finding 8 more cancers associated with obesity (see  obesity and cancer nejm2016  in  dropbox , or  Lauby-Secretan  B. N  Engl  J Med 201; 375: 794). They relied on over  1000 epidemiological/observational studies to assess this association, since there really are no large r andomized clinical intervention  trials with long-term  followup  assessing the effects of weight- loss vs maintaining weight to see if there is a difference in cancer incidence. -- background, worldwide estimates: --in 2014:  640 million adults in 2014 (an increase by a factor of 6 since 1975) were obese --in 2013: 110 million children and adolescents (an increase by a factor of 2 since 1980) were obese --in 2014: prevalence of obesity was 10.8% among men, 14.9% among women,...

vasovagal syncope is pretty common, but there are no documented effective treatments. Fludrocortisone has potential by improving venous return: its efficacy was evaluated in the Prevention of Syncope Trial 2 -- POST 2 trial (see  syncope fludrocortisone jacc2016​  in  dropbox , or Sheldon R. JACC 2016; 68: 1). details: --210 patients (71% female, median age 30, BMI 24, HR 70 bpm, BP 112/70) with a mean of 15 syncopal episodes over 9 years --randomized to fludrocortisone at the highest tolerated doses (from 0.05-0.2 mg/d, titrated over 2 weeks, with most achieving the 0.2  mg dose) vs placebo and followed for 1 year --inclusion criteria: >13  yo , >2 lifetime syncopal episodes; exclusions: diabetes, hepatic disease BP>135/85, "significant comorbidities", or if when standing 5 minutes they had postural tachycardia of >30 bpm, or orthostatic hypotension of >20/10 mmHg. --results     --9...

the NY Times had a recent story looking at the role of the microbiome (sorry to those microbiome-phobic) in the development of type 1 diabetes (T1D), see http://www.nytimes.com/2016/06/05/opinion/sunday/educate-your-immune-system.html?smprod=nytcore-iphone&smid=nytcore-iphone-share . this article was based on a recent clinical study (see  microbiome type1 diabetes cell2016  in dropbox, or doi.org/10.1016/j.chom.2015.01.001). --33 infants genetically predisposed to T1D through specific HLA alleles, following changes in their gut microbiota frequently --though microbiota varied greatly between individuals, it remained stable throughout infancy in each individual --after 3 years, 4 of the children developed T1D --at the time of T1D diagnosis, there was a marked 25% drop in diversity of the microbiome occurring after anti-islet cell autoantibody development/seroconversion (not found in those who did not seroconvert) but 1 year before clinical T1D, alo...

and, the final blog on NAFLD (finally): Clinical practice guidelines from European Association for the Study of Liver Diseases, and others (see  nafld guidelines EASL2016  in dropbox, or J Hepatol 2016; 64: 1388). Several of the studies referenced here were included in the prior 2 blogs. --NAFLD is characterized by increased hepatic fat, insulin resistance (IR), and steatosis in >5% of hepatocytes. Diagnosis of NASH requires a liver biopsy. The NAS score (NAFLD activity score) cannot be used to diagnose NASH and has a low prognostic value --diagnosis is based on exclusion of secondary causes (hepatitis C, drug and other causes of liver injury) and daily alcohol consumption of >30g/d for men or >20 g/d for women (it's arbitrarily considered alcoholic liver disease if above that). --recommendations:     --patients with IR (and/or metabolic syndrome or obesity) should get "diagnostic procedures for the diagnosis ...

This is the second part of the series on NAFLD,  a review of therapies, with more detail on a couple of topics (eg the roles of fructose and the microbiome) -------------------------------------------------------------------------------------------------------------------------- (see  nafld lifestyle interventions digdissci2016  in dropbox, or Hannah WN. Dig Dis Sci 2016; 61:1365) It is pretty clear that weight loss in those overweight/obese is the best documented therapy for NAFLD. Those who can lose 3-5% of their body weight tend to improve hepatic steatosis; and those who can lose >5% in one large study found 58% had resolution of NASH and 82% had a 2-point reduction in their NAS (NAFLD Activity Score on biopsy). Those who lost >10% of their body weight (n=29) had 100% had resolution of NAS,  90% had resolution of NASH, and 45% had regression of fibrosis. Other studies suggest that the type of diet is not so important: it's ...