Postoperative Neutrophil to Lymphocyte Ratio as an Overall Mortality Midterm Prognostic Factor following OPCAB Procedures

Round 1

Reviewer 1 Report

Authors examined the usefulness of NLR to predict prognosis for OPCAB.

 

Although this manuscript is potentially interesting, several issues arise.

 

Please compare NLR with other inflammatory markers such as CRP.

 

Please show a survival curve after OPCAB.

 

Please show causes for death after OPCAB.

 

Abstract

Cutoff value of NLR as prognostic marker may be helpful.

 

 

Introduction

It is helpful for the reader that OPCAB is further explained.

Explanation for the complication of OPCAB may be helpful.

 

 

Figure 1 LEVF (AUC=0.892) is good prognostic marker. However, NLR (AUC-0.715) seems to be not good marker.

 

Discussion

Please discuss how do you manage patients with elevated NLR.

Author Response

Dear Reviewer 1,

Thank you for your valuable comments. We corrected the manuscript according to them.

 

1. Please compare NLR with other inflammatory markers such as CRP.

 Response: line 127-130

The whole blood count was the only standard labolatory test presenting inflammatory reaction on 1^st and 7^thpostoperative day. The other inflammatory parameters were not compared in the study as C-reactive protein (CRP) or procalcitonine was perfomed only if infection was suspected.

 

2. Please show a survival curve after OPCAB.

Response: 221-230

Figure 1.

NLR and probability of mid-term survival.

                                         Abbrevialtions:

                                                NLR – neutrophil-to-lymphocyte ratio.

 

 

3. Please show causes for death after OPCAB.

Response: line 179-180

There were 26 deaths in presented analysis related to 15 (58%) coronary syndromes and 11 (42%) secondary to stroke.

4.Abstract

Cutoff value of NLR as prognostic marker may be helpful.

Response: line 69-70

Postoperative NLR increase above 4.6, as an inflammatory reaction marker, is related to mid-term mortality in OPCAB patients.

 5.Introduction

It is helpful for the reader that OPCAB is further explained.

Explanation for the complication of OPCAB may be helpful.

Response: line 74-76

 Surgical revascularization of coronary artery disease can be performed with cardiopulmonary bypass or as “beating heart” technique called off-pump coronary artery bypass grafting (OPCAB). It allows to omit cardiopulmonary circuit with all possible side effects including inflammatory reaction activation [1].

 

6. Figure 1 LEVF (AUC=0.892) is good prognostic marker. However, NLR (AUC-0.715) seems to be not good marker.

Response: line 274-276

The strongest predictor for mid-term survival was left ventricle ejection fraction (AUC=0.895). Results of our study present the NLR as an independent mortality predictor following the OPCAB procedure with moderate significance (AUC = 0.715). This study points out the significance of inflammatory reaction activation as one of the possible prognostic factors

Response: 221-230

Figure 1.

NLR and probability of mid-term survival.

 

 

 

 

                                         Abbreviations:

                                                NLR – neutrophil-to-lymphocyte ratio.

 

 

7. Discussion

Please discuss how do you manage patients with elevated NLR.

Response: 340-343

This was a retrospective study but highlighted possible new approach to patients undergoing OPCAB procedures. We intend to follow up more closely this group f patients (NLR >4,6) regarding to more frequent test including treadmill test and angiographies, if indicated. This group will be more scrutinously monitored regarding cardiovascular risk factors including hypertension, as well.

 

Kind regards

Tomasz Urbanowicz

Reviewer 2 Report

The author aimed to compare postoperative 57 results of NLR with mid-term OPCAB results.

The study is even timely and important but I would highlight the importance of NLR in cardiac surgery area citing and discussing recent articles on this important topic. For example, the study by Serra R, Ielapi N, Licastro N, Provenzano M, Andreucci M, Bracale UM, Jiritano F, de Franciscis S, Mastroroberto P, Serraino GF. Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio as Biomarkers for Cardiovascular Surgery Procedures: A Literature Review. Rev Recent Clin Trials. 2021;16(2):173-179. The discussion section in the current format is too short and needs to be expanded.

  

Author Response

Reviewer 2.

 

Dear Reviewer thank you for your valuable comments. We corrected the manuscript according to them.

 

The study is even timely and important but I would highlight the importance of NLR in cardiac surgery area citing and discussing recent articles on this important topic. For example, the study by Serra R, Ielapi N, Licastro N, Provenzano M, Andreucci M, Bracale UM, Jiritano F, de Franciscis S, Mastroroberto P, Serraino GF. Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio as Biomarkers for Cardiovascular Surgery Procedures: A Literature Review. Rev Recent Clin Trials. 2021;16(2):173-179. The discussion section in the current format is too short and needs to be expanded.

 

Response:

Line 273-276

The strongest predictor for mid-term survival was left ventricle ejection fraction (AUC=0.895). Results of our study present the NLR as an independent mortality predictor following the OPCAB procedure with moderate significance (AUC = 0.715). This study points out the significance of inflammatory reaction activation as one of the possible prognostic factors.

 

Line 289-293.

The association between increased preoperative NLR and cardiovascular risk and cardiovascular and cerebrovascular events (MACE) in 30-days postoperative period in non-cardiac surgery was presented by Larman [12].

Tan in his review postulated association increased preoperative values of NLR (>3.3 in cardiac surgery) with increased mortality at a mean follow-up of 34.8 months [13].

 

Line 329-333.

The results from our retrospective analysis, present the link between inflammatory reaction activation and risk for mid-term mortality. The NLR was found be found a marker of moderate significance in presented study. The significance of NLR in perioperative period of cardiovascular procedures was already presented [32]. Never less, the deaths were related to cardiovascular complications with know linkage to inflammatory processes [22].

 

Kind regards

Tomasz Urbanowicz

Round 2

Reviewer 1 Report

Although this manuscript has been improved, several issues arise.

 

・What is the title of Table 1 and 2?

・Table 3: “mean ±　SD” may not be correct.

・The relationship between NLR and LEVF or NLR and Troponin.

・Authors performed statistical analysis for the difference between 2 groups using the Mann-Whitney test. Dara may be better to be presented as “Median: range”  

・Line 203-204 and Table 3 title should be further explained.

Author Response

Dear Reviewer1,

Thank you for your valuable comments. We corrected the manuscript according to them.

1. What is the Title of Table 1 and 2

Response: line 98-99

Table 1.

Demographical and clinical data & hospitalization.

 

Response: line 126-127

Table 2.

Perioperative laboratory results.

 

2. Table 3: mean +/- SD may be corrected.

We believe you wanted us to change Table 2 that was corrected.

Response: 126-129

Parameters	Group 1 Survivors (n=198)	Group 2 Deceased (n=26)	p-value
Preoperative: 1.    WBC, x109/l Me [Q1 – Q3] 2.    Neutrophils, x109/l Me [Q1 – Q3] 3.    Lymphocyte, x109/l Me [Q1 – Q3] 4.    Hb, mmol/l Me [Q1 – Q3] 5.    Plt, x109/l Me [Q1 – Q3] 6.    NLR Me [Q1 – Q3] 7.    Troponin, ng/mL Me [Q1 – Q3]	7.8 [6.6 - 9.4] 5.1 [4.2 - 6.2] 1.8 [1.4 - 2.3] 8.8 [8.2 - 9.2] 221 [188 - 259] 2.7 [2.1 - 3.71] 0.01 [0.01 - 0.02]	7.6 [6.8 - 9.2] 4.9 [4.3 - 6.1] 1.7 [1.4 - 2] 8.7 [7.9 - 9.3] 215 [197 - 265] 2.7 [2.1 – 4.0] 0.01 [0.01 - 0.03]	p = 0.6780 p = 0.7849 p = 0.4513 p = 0.9893 p = 0.9397 p = 0.7119 p = 0.1442
Postoperative 1st day): 1.      WBC, x109/l Me [Q1 – Q3] 2.      Neutrophils, x109/l Me [Q1 – Q3] 3.      Lymphocyte, x109/l Me [Q1 – Q3] 4.      Hb, mmol/l Me [Q1 – Q3] 5.      Plt, x109/l Me [Q1 – Q3]   6.      NLR Me [Q1 – Q3] 7.      Troponin, ng/mL Me [Q1 – Q3]	8.4 [6.6 - 10.5] 4.7 [3.7 - 6.4] 1.9 [1.5 - 2.6] 6.8 [6.5 - 7.2] 288 [238 - 346] 2.5 [1.8 - 3.3] 1.5 [0.7 - 3.7]	9.3 [7.9 - 10.9] 6.6 [5 - 7.7] 1.8 [1.2 - 2.4] 7 [6.5 - 7.4] 358.5 [265 - 420] 4.4 [2.6 - 7.2] 2.7 [0.6 - 10.6]	p = 0.0331 p = 0.0012 p = 0.0779 p = 0.3570 p = 0.0157 p = 0.0003 p = 0.1206
Postoperative 7th day): 1.      WBC, x109/l Me [Q1 – Q3] 2.      Neutrophils, x109/l Me [Q1 – Q3] 3.      Lymphocyte, x109/l Me [Q1 – Q3] 4.      Hb, mmol/l Me [Q1 – Q3] 5.      Plt, x109/l Me [Q1 – Q3] 6.      NLR Me [Q1 – Q3] 7.      Troponin, ng/mL Me [Q1 – Q3]	8.4 [6.6 - 10.4] 4.7 [3.7 - 6.3] 1.9 [1.5 - 2.6] 6.8 [6.4 - 7.2] 290 [237 - 351] 2.5 [1.8 - 3.3] 0.01 [0.01 - 0.01]	8.5 [6.9 - 11] 5.2 [3.5 - 6.4] 2.2 [1.6 - 2.7] 7 [6.6 - 7.3] 273.5 [236 - 309] 2.5 [2 - 3.6] 0.01 [0.01 - 0.01]	p = 0.4047 p = 0.3956 p = 0.4216 p = 0.1483 p = 0.2592 p = 0.6694 p = 0.7638

 

3. The relation between NLR and LVEF or NLR and Troponin.

 

Pair of Variables	Spearman Rank Order Correlations (baza 2018 OPCAB z przezyciem dla NLR_242) MD pairwise deleted Marked correlations are significant at p <.05000
	Valid N	Spearman R	t(N-2)	p-value
N/L_przed & TROP 0	240	0 .043111	0 .665699	0 .506248
N/L_przed & EF_przed	241	0 .039159	0 .605841	0 .545195

 

 

 

 

Pair of Variables	Spearman Rank Order Correlations (baza 2018 OPCAB z przezyciem dla NLR_242) MD pairwise deleted Marked correlations are significant at p <.05000
	Valid N	Spearman R	t(N-2)	p-value
N/L_po & EF_po	242	-0 .182080	-2 .86873	0 .004488
N/L_po & Trop MAX	242	0 .105162	1 .63824	0 .102682

Correlation – 0.18 (p=0.0045) but it’s below 0.20 that is interpretated as no correlation

 

4. Authors performed statistical analysis for difference between 2 groups using the Mann -Whitney test. Data may be better to be presented as Median range.

Response: line 156-157.

Continuous variables were reported as mean ± standard deviation (SD) or medians and interquartile ranges Me [Q₁ – Q₃] in case data did not follow normal distribution.

5. Line 203-204 and Table 3 title should be further explained.

Response: line 190-195

 Univariable and multivariable Cox’s proportional hazard regression analysis was performed and is presented in Table 3. In univariable Cox’s analysis, there were several factors including preoperative (stroke, peripheral artery disease), echocardiographic results (including left ventricle diameter and ejection fraction) and laboratory results on 1^stpostoperative day (neutrophils, platelets and NLR). The multivariable analysis left ventricle ejection fraction (LVEF) and whole blood count parameters (white blood count, neutrophils, platelets and NLR) appeared significant.

 

 

Kind regards

Tomasz Urbanowicz

Reviewer 2 Report

amended manuscript is acceptable

Author Response

Dear Reviewer,

thank you for your positive opinion.

 

Kind regards

Tomasz Urbanowicz