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ARTICLE DETAILS
TITLE (PROVISIONAL)
AUTHORS
Predicting the outcome of hip fracture patients by using N-terminal
fragment of pro-B-type natriuretic peptide
Nordling, Pauliina; Kiviniemi, Tuomas; Strandberg, Marjatta;
Strandberg, Niko; Airaksinen, Juhani
VERSION 1 - REVIEW
REVIEWER
REVIEW RETURNED
Lorena Maries, MD, PhD
Intermedica Medical Center, Romania
10-Aug-2015
GENERAL COMMENTS
As you acknowledge in the "Discussion" section, "the idea was to
obtain
NT-proBNP samples preoperatively in all patients, but due to
weekends and public holidays, preoperative
tests were obtained in 64 % of the patients only". And instead, "NTProBNP was measured during hospitalization in all 182 patients,
preoperatively in 117
(64 %) and postoperatively in 86 (47 %) patients; in 96 patients
preoperative only, in 21 both pre- and
postoperatively and in 65 postoperatively only". But, in the same
time, "blinded TnT
measurements and ECG recordings were performed on admission,
before operation and on 1st and 2nd
postoperative days". Yet, you name as one of the strengths of your
study, "the combined effect of TnT and NT-pro-BNP".
As the samples were obtained in different moments of the patients'
admission to the hospital (preopertively, postoperatively), you cannot
combine them, and say they all reflect the same thing, especially as
it is known, as you state yourselves, that " major trauma and
surgery.... may cause stress on the heart and lead to elevated NTproBNP levels". This is making your results, not objective.
Also, I didn't find in your study anything about, what the age of the
patients was, about their medical history or the medication they have
been taking before coming to have this hip fracture intervention. All
of these are known to influence the levels of NT-pro-BNP.
Half of your references are more than 5 years old, which doesn't
mean "up to date".
REVIEWER
Sylvia Farzi
Medical University of Graz
15-Aug-2015
REVIEW RETURNED
GENERAL COMMENTS
Congratulations on your work! You were able to demonstrate the
additional value of NT-proBNP on top of troponin in the setting of hip
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fracture surgery patients for the first time. Elevated NT-pro-BNP
levels do have the potential to single out those patients at risk that
otherwise go undetected. The clinical applicability of this knowledge
remains to be tested in interventional studies.
VERSION 1 – AUTHOR RESPONSE
Reviewer #1:
-As the samples were obtained in different moments of the patients' admission to the hospital
(preopertively, postoperatively), you cannot combine them, and say they all reflect the same thing,
especially as it is known, as you state yourselves, that " major trauma and surgery.... may cause
stress on the heart and lead to elevated NT-proBNP levels". This is making your results, not objective.
Response 1_1: This is an important comment. Our goal was to obtain preoperative NT-proBNP
measurements in all the patients. Due to logistic issues (weekends, public holidays etc) this was not
possible. We agree that this is a limitation and a target for future studies expanding our findings.
Nevertheless, the present study shows that any perioperative troponin or NT-proBNP elevation in this
patient group identifies patients at risk for mortality compared to patients without these elevations.
Moreover, the highest NT-proBNP level appeared a strong predictor of mortality. There is a comment
on variable timing of perioperative NT-proBNP measurements in the Limitation chapter of Discussion.
Also, I didn't find in your study anything about, what the age of the patients was, about their medical
history or the medication they have been taking before coming to have this hip fracture intervention.
All of these are known to influence the levels of NT-pro-BNP.
Response 1_2: Table 1 presents baseline clinical characteristics of the study population, including
mean ages and their medical history, while tables 2 and 3 compare the characteristics of patients who
died vs. survived 30 days and 1000 days after hospital admission.
We have now added information on the medication that the patients had been taking before hospital
admission to table 1.
Half of your references are more than 5 years old, which doesn't mean "up to date".
Response 1_3: It is true that we have cited several older articles because of the lack of more recent
studies on the subject.
Reviewer #2:
-Congratulations on your work! You were able to demonstrate the additional value of NT-proBNP on
top of troponin in the setting of hip fracture surgery patients for the first time. Elevated NT-pro-BNP
levels do have the potential to single out those patients at risk that otherwise go undetected. The
clinical applicability of this knowledge remains to be tested in interventional studies.
Response 2_1: Thank you very much for your comment. We do hope to raise awareness of the
subject.
We have also made an additional minor change in the manuscript. In the original version of the
manuscript each patient was assigned an ASA physical status class based on the information in the
medical records as interpreted by the investigators. We have recently acquired the ASA scores that
the on-call anesthesiologist assigned to each patient preoperatively. In this revised manuscript we
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have used these more accurate, preoperatively assigned, ASA scores. This has also been changed to
the Methods section. This minor qualification caused no change in any of the findings or conclusions
of the study
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Predicting the outcome of hip fracture
patients by using N-terminal fragment of
pro-B-type natriuretic peptide
Pauliina Nordling, Tuomas Kiviniemi, Marjatta Strandberg, Niko
Strandberg and Juhani Airaksinen
BMJ Open 2016 6:
doi: 10.1136/bmjopen-2015-009416
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