Friday, 21 July 2017

My lost lecture on FLCs test in kidney diseases

Last year, I was honoured to give a lecture on the clinical use of the Free Light Chains test in kidney diseases. It was my first time as a presenter in one of the most popular Universities of Rome.

It was very exciting to take the stage after such a big name of Clinical Medicine as Prof Giampaolo Merlini. Fortunately, it was a success.

Many delegates asked me to share my slides, but, moving back at home, I lost my USB drive... I found it only two days ago.

So, here's my Lost Lecture 

A lecture on the use of Body Composition Monitor

A few months ago, I gave a lecture con BCM use in dialysis.
Here's the link to the slides: 

Tuesday, 9 May 2017

Physical examination skills and NNT: number needed to teach

A number of physical examination techniques have been abandoned because of poor reproducibility. Studies have shown that many physicians are unable to use them appropriately. Thus it seems, they simply don't work. Is this type of evidence really applicable to the teaching of physical examination?
Is there any threshold or any NNT (number needed to teach) to justify the emerging practice of omitting the teaching of this techniques?
Why shouldn't we continue to teach these techniques even if there will be only 1 of 1000 students skilled enough to perform them successfully?

Tuesday, 22 November 2016

A Spoiler of Two RCTs on Extracorporeal FLCs Removal (Eulite and MYRE)

At the time of Multiple myeloma (MM) diagnosis, severe AKI secondary to Myeloma Cast Nephrpathy is a common complication. Recovery of renal function is a key prognostic factor. Two RCTs have recently investigated the use of extracorporeal dialysis strategies to rapidly remove circulating monoclonal free light chains (FLC).
Waiting for final results publication, this is a spoiler of available data:
-          Eulite Study90 patients with severe de novo dialysis-dependent AKI secondary to biopsy–proven Myeloma cast nephropathy were randomised to receive either standard high-flux dialysis (n=47) or free light chain (FLC) removal haemodialysis using a HCO dialyzer (n=43).  Dialysis sessions in HCO group were longer (6 hours on day 0, then 8 hours on days 2, 3, 5–7, 9+10. After day 12, participants received 8 hours of haemodialysis on alternate days. After day 21, if patients still required renal support the dialysis schedule was reduced to 6 hours three times per week) and more frequent than the conventional dialysis received by the control arm (4h x3/wk). All patients received standardised chemotherapy (bortezomib based regime). The primary endpoint of the study I, i.e. independence of dialysis at 3 months from enrolment, was achieved in 55.8% of patients in HCO group and 51.6% in standard HF-HD group (p=0.65). An increase in mortality was reported in the treatment group mainly due to delay in chemotherapy and infection.
-          MYRE Study. Patients with severe de novo dialysis-dependent AKI secondary to biopsy–proven Myeloma cast nephropathy received 21-day courses of Bortezomib and dexamethasone (BD), reinforced by cyclophosphamide after 3 cycles in the absence of haematological response (HR). Patients were randomized to receive  conventional high-flux dialysis or  intensive HD (8 sessionsof 5 hours over the first 10 days, then thrice weekly) using a HCO dialyzer. Baseline characteristics in the control arm (n=48) and HCO arm (n=46) were close, including similarly high serum FLC levels (median 6,015mg/L).  HD independence was achieved in 33% and 43% (p= 0.31) at 3 and in 37.5% and 60 % (p=0.03) at 6 months, in the control and HCO arms, respectively. HR rate at 3 months based on FLC was 48% in control and 59% in HCO groups (p=0.29). At 12 months, 17 pts have died (10 vs 7).  

Differences in clinical outcomes could be theoretically justified by the more intensive treatment regimen adopted in Eulite Study. 

Tuesday, 1 November 2016

Cryoglobulinemic Syndrome: the essentials (My first ebook)

My first e-book, Cryoglobulinemic Syndrome: the essentials, is now freely available for Download

I hope you will enjoy it.

Monday, 3 October 2016

A Lecture on CKD-MBD

If you are interested in my last presentation on CKD-MBD please follow this link:


Comments are welcome.

Monday, 27 June 2016

The Original Water Deprivation Test from 1963

Risultati immagini per assetato

In the 1940s, in order to distinguish between primary polydipsia and diabetes insipidus a number iof dehydration tests were proposed  However, it was only in 1963 that Dashe et al published in JAMA a standardized water deprivation test, solving the problem of differential diagnosis of polyuric syndromes.

How to Perform a Water Deprivation Test according to the original Dashe's protocol: 

1.      On the morning of the test day, the patient is allowed to drink fluids ad lib until 8:30 am, and to eat breakfast prior to that time, but coffee, tea, and smoking are interdicted.
2.      For 7 hours after 8:30 am, the subjects are allowed no food or fluids.
3.      Serum and urine specimens are obtained for determination of osmolality
4.       Body weight is measured at the beginning and end of the experiment
5.      The subject voids urine at 8:30 am, and urine is subsequently collected by voiding at 9:30 and 11:30 am, and 12:30, 2:30 and 3:30 pm.
6.      Serum osmolality and serum sodium levels are to be measured at 9:00 am, 12 noon, and 3:00 pm

Dashe et al. compared changes in in the ratio Uosm-to-Sosm in several groups:

1)      Group A: Normal subjects. There weren’t significant changes in serum osmolality (285->286 mOsm/Kg). All normal subjects were able to excrete a highly concentrated urine (range of final-hour urine concentration, 756 to 1,496 mOsm/kg). The ratio of urine to serum osmolality ( urine-to-serum ) for the last hour of the test was 3.8 ± 0.9, with a range from 1.9 to 5.2
2)      Group B: patients with known diabetes insipidus. Six of the 13 patients had initial serum osmolalities within or below the normal range; however, all subjects developed a serum osmolality of 300 mOsm/kg or greater by the end of the test. The final osmolar concentration of the serum exceeded the initial level by an average of 12.0 mOsm/kg; the greatest change was +47 and the least was + 1.  Not surprisingly, patients with diabetes insipidus excreted urine which was less concentrated. The mean urine-to-serum ratio was  0.93 ± 0.45.
3)      Group C: Primary polydipsia. There was no change in serum osmolality during the test. The urine-to-serum ratio was comparable to group 1 ( > 2).

Interestingly, whereas the test is currently stopped when body weight decreases by 3% from baseline, in the original study by Dashe et al. an average of 2.6% of body weight was lost by the patients with severe diabetes insipidus. Indeed, the authors used a fixed duration of 6.5 h

These are Dashe’s conclusions, reporting clinical results for each diagnosis

1)      Mildest degree of diabetes insipidus currently identifiable:  Stability of serum osmolality with subnormal urine-to-serum osmolal ratio
2)      Moderate diabetes insipidus: supernormal serum concentration or supernormal increment in serum osmolar concentration. The serum concentration, however, is not greater than 300 mOsm/kg at any time.
3)      Severe diabetes insipidus: a serum osmolality which is greater than 300 at the end of the experiment
4)      A urine-to-serum ratio above 1.0 excludes the diagnosis of diabetes insipidus. Although some patients with rather severe diabetes insipidus may achieve a urine-to-serum ratio greater than 1.0, they do so only at a time when serum osmolalities were greater than 300 mOsm/kg.

Values before and after a Water Deprivation Test according to Dashe et al.

Initial Sosm
Post-test Uosm-to-Sosm ratio
Normal subjects
> 1
Diabetes Insipidus
High (or High Normal)
< 1
Primary polydipsia
Low (or Low Normal)
> 1

Reference: Dashe et al: A Water Deprivation Test for the Differential Diagnosis of Polyuria. JAMA Vol. 185, No 9. Aug 31, 1963.