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Article
Peer-Review Record

Early Diagnosis of Neutropenic Enterocolitis by Bedside Ultrasound in Hematological Malignancies: A Prospective Study

J. Clin. Med. 2021, 10(18), 4277; https://doi.org/10.3390/jcm10184277
by Edoardo Benedetti 1,2,*, Benedetto Bruno 3, Francesca Martini 1, Riccardo Morganti 4, Emilia Bramanti 5, Francesco Caracciolo 1, Sara Galimberti 1, Piero Lippolis 6, Emanuele Neri 7, Chiara Arena 7, Francesca Cerri 7, Vittorio Ricchiuto 8, Matteo Pelosini 1, Enrico Orciuolo 1 and Mario Petrini 1
Reviewer 1: Anonymous
Reviewer 2: Anonymous
J. Clin. Med. 2021, 10(18), 4277; https://doi.org/10.3390/jcm10184277
Submission received: 3 July 2021 / Revised: 23 August 2021 / Accepted: 13 September 2021 / Published: 21 September 2021
(This article belongs to the Section Hematology)

Round 1

Reviewer 1 Report

Early diagnosis of neutropenic enterocolitis by bed-side ultra-

sound in hematological malignancies: a prospective study

 

General comments:

Thank you very much for the opportunity to review this study. the study prospectively examines the use of ultrasound for neutropenic colitis in particular. The study was performed on a large patient collective (1754 cases). Although the findings are interesting, there are some major issues that need to be addressed.

 

 

Major aspects:

 

Material and Methods:

- very heterogeneous patient collective! In particular, the patients after allogeneic stem cell transplantation pose a problem and would have to be evaluated separately. How are important differential diagnoses excluded, such as acute GvHD of the intestine and CMV colitis? Did the patients have other acute GvHD manifestations at the time of the diagnosis of neutropene colitis?Other differential diagnoses, such as Closs. Diff. colitis can also play a role in the other patients. A subgroup analysis would have to be performed  

Ultrasound:

 

for a study with sonography focus, less information are given to the methodology of ultrasound!

- What does it mean, the first ultrasound examination was performed when the study started? Does that mean start of symptoms or did all patients (including the "control group" without symptoms) receive a baseline ultrasound after agreeing to the study? This would be of crucial importance

- who performed the ultrasound? Bowl ultrasound is one of the most difficult compartments and requires an experienced examiner

-Were the baseline and follow up examinations performed by the same examiner? This would also be significant because of the limitation that sonography is a method that is dependent on the examiner

- Did the control group also receive an ultrasound examination as part of the neutropenia?

- was ultrasound performed according to a standard protocol?  

- did the sonography also reveal other diagnoses for abdominal pain?

 

Results:

- data are missing. When did neutropenic colitis occur- Numbers of neutropenic colitis are very low, especially after Allo and Auto-Tx, since patients often have diarrhea associated with drugs.

-did ALL patients receive the mentioned prophylaxis or only after Allo-TX?+

-What therapies and diagnoses did the patients in the control group have?

- How was the diagnosis made and how was it differentiated from differential diagnoses?- the conclusion is not clear ... how ultrasound made the early diagnosis? This is not clear, as sonography was only performed when there were symptoms; it must be adjusted in the revised manuscript-

 

Mortality

how can you make sure it was the NEC? a septic shock can also have other causes in neutropenia.

 

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Dear authors,

 

I applaud and welcome echocardiography by the bedside, however your manuscript needs major clarification of several endpoints.

Research question: Endpoint of the study was to prospectively verify the hy-58 pothesis that bedside ultrasonography could

detect early signs of NEC: All practicing hematologists with experience in intensive chemotherapy know that this is a complication which is to be expected in certain patient populations. Early depends on cancer and treatment type. Fever develops as a consequence of bacteremia in a leaky gut due to mucosal damage. This process invariably leads to NEC in some patients. So early is to my opinion a function of treatment and duration of neutropenia.

leading to prompt 59 medical treatment ( compared towhich standard practice?) ,

You discuss medical treatment of bacteremia, but the treatment of NEC is not defined in this population but a very important step is decreasing the duration of neutropenia ( GCSF?)

eventually, reducing mortality.  I have to guess that this is the primary endpoint because it is not clearly stated: IN case this is the primary endpoint I miss a power calculation. It is therefore also unclear how you conclude that your intervention reduced mortality and in my opinion your research question remains unanswered.  

 

 

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Early diagnosis of neutropenic enterocolitis by bed-side ultra-

sound in hematological malignancies: a prospective study

 

General comments:

Thank you very much for the opportunity to review this revised manuscript. Thank you for the corrections. Now I recommends  publication of the manuscript.

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