Extra Corporeal Membrane Oxygenation in the Treatment of Human Immunodeficiency Virus-Related P. jirovecii Pneumonia

Round 1

Reviewer 1 Report

The authors show a case series of ECMO support in HIV patients with PJP. The article is well written, easily readable.

I've only detected one mistake during the manuscript: Please correct Table 1 (row indicating CD4+ T-cell count is incorrect)

 

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

The authors report on the successful application of ECMO in AIDS patients following advanced/untreated HIV.  This case series rises great interest as far as less data are available considering success rate of ECMO in AIDS patients due to HIV. Presented report may encourage clinicians throughout the world to apply this method in such settings.

ECMO therapy is known to be one of the most challenging approach in the field of intensive medicine and reporting colleagues and their medical stuff did undoubtedly an excellent job as far as all four patients survived such a critical complication as PJP and intensive therapy as ECMO itself. I would like to address several points which in my opinion could improve this very interesting and valuable report:

Major:

1. Although all patients have criteria of AIDS, as far as CD4+ cells were below 200 cells/mm3 at admission, the authors do not use this term in patient’s description. I propose to mention this aspect in each case aiming to highlight the severity of immunodeficiency on the one side and to ease understanding of CD4 values for readers on the other side.
2. CT scans at diagnosis and follow-up are presented separately in two figures which make the visual comparison more complicated. It would be better to place CT scans at diagnosis (e.g. left column) and at follow-up (e.g. right column) in front of each other within one figure.
3. Please provide the dosages of TMP-SMX and cortison which were used to make an article more valuable for readers. I suggest TMP-SMX was continued as a prophylaxis in each case following recovering after PJP but still AIDS according to CD4 values given in table 1. Please, mention that in the text.
4. Case 3. Please provide information considering treatment of cerebral toxoplasmosis.
5. Viral load dropped significantly and CD4+ count increased following initiation of ART according to the Table 1. This is a very important message showing that patients in critical conditions like PJP with ECMO treatment benefit rapidly from ART afterwards. To highlight this point, I would propose to present their dynamics as a figure with two lines: a. viral load and b. CD4 count (alongside Y axis) with a time point for ECMO/IMV and ART start (alongside X axis) for each patient. I understand that such a figure would cost additional efforts and that is why I do not insist on that. However, in my opinion, it would make the article more valuable for readers and inspire physicians more to work with such patients.
6. ECMO suggests a very invasive approach with an increased risk for medical stuff to have a contact to body fluids of patients. Please, mention this as a challenge for medical stuff caring about HIV patients with ongoing ECMO.

Minor points:

Line 79, 92: second opening bracket should be added, e.g. ((Figure 1 (a)).

Line 85: VV-ECMO. Please provide explanation for vv (Venovenous) before using directly an abbreviation

Table 1: Put CD4+ count and viral load in distinct lines

Table 1: no explanations to used abbreviations are given below the table. This has to be added.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 3 Report

The manuscript entitled “Extra corporeal membrane oxygenation in the treatment of Human Immunodeficiency virus related P. jirovecii pneumonia” by Sara Lacerda Pereira et al. presents extracorporeal membrane oxygenation (ECMO) as a viable therapeutic strategy for HIV-infected patients discussing its indications and possible role in the prevention of barotrauma in cases of P. jirovecii pneumonia (PJP) and acute respiratory distress syndrome (ARDS).

The manuscript is generally clear and well written, and may be helpful in order to investigate the possible benefits of ECMO support even in those patients who were previously considered less likely to benefit, such as HIV-infected patients, and to understand how to best utilize and optimize ECMO therapy in patients with severe immunosuppression. In fact, authors demonstrate that ECMO should be considered in HIV-positive patients with worsening gas exchange despite protective mechanical ventilation as it may achieve a favorable clinical outcome. From this perspective, the article is highly relevant and informative to the reader. Therefore, after the revision of the following minor points, I would suggest that the manuscript is suitable for publication in Infectious Disease Reports.

Abstract, Page 1, line 15: the sentence “ventilator-associated lung injury (VILI)” should please be corrected in “ventilator-induced lung injury (VILI)”, as ventilator-associated lung injury and ventilator-induced lung injury are not synonyms

Case Reports (Case 1), Page 2, line 70: authors should please check the sentence “29-year-old male HIV-positive since 2016” as in Table 1, Page 7 Diagnosis is stated in 2015

Page 2, line 85: authors should please spell out the acronym VV-ECMO

Table 1, Page 7: authors should please spell out the acronyms HFOT and NIVM, and check the misalignments in Table 1

Discussion, Page 8, lines 187-189: it seems to this reviewer that reference number 11 cited about the sentence “In Europe, in 2018, 49% of HIV-infected patients were diagnosed at a late stage, and the same in Portugal, with 34.3% diagnosed with T-lymphocyte CD4+ count below 200 cells/mm3 and 15.9% of new diagnosis with AIDS”, is not appropriate and should be checked by authors (reference number 11 regards a retrospective study, from May 2011 to October 2014, conducted in South Africa, thus it does not reflect the situation in Europe in 2018)

Discussion, Page 8, lines 200-202: the following sentence does not seem correctly worded, please check: “With ART, immunosuppression in HIV infection is potentially reversible, and the prognosis appears to be better than PJP in patients immunosuppressed for other causes [13].”

Discussion, Page 8, lines 219-221: the following sentence does not seem correctly worded, please check: “In fact, there is growing evidence that use of ECMO is not necessarily futile immunocompromised patients with HIV and the experience from our case series is consistent with those reports.”

References, Page 9, lines 273-274: I would suggest to update References 6 and 7 (i.e. Garland JM, et al. Care of Critically Ill Patients with Human Immunodeficiency Virus. Ann Am Thorac Soc. 2020 Jun;17(6):659-669; Barbier F, et al. Management of HIV-infected patients in the intensive care unit. Intensive Care Med. 2020 Feb;46(2):329-342)

Some typos have to be corrected all over the text (i.e., lines 143, 154, 174, 273)

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 4 Report

This is a well written review on the role of extra corporeal membrane oxygenation in HIV patients. It would be beneficial to the readers to explain how it works in the introduction

The authors mention about ART, a table of current ARTs would be insightful. 

Please delete pretend in line 65. 

"With this review, we pretend to present our experience with ECMO support in HIV infected patients and discuss its indications and possible role in the prevention of barotrauma in cases of PJP and ARDS."

Author Response

Please see the attachment.

Author Response File: Author Response.docx