8521
The assessment of platelet-lymphocyte ratio (plr) and severity index of fournier gangrene (fgsi) as prognostic
factors in fournier gangrene patients
Batara Joseph Sihotang1, Dhirajaya Dharma Kadar2, Syah Mirsya Warli2,3,*
Department of Surgery, Faculty of Medicine, Universitas Sumatera Utara, Haji Adam Malik General Hospital1
Division of Urology, Department of Surgery, Faculty of Medicine, Universitas Sumatera Utara – Haji Adam Malik General Hospital, Medan, Indonesia2
Department of Urology, Universitas Sumatera Utara Hospital, Universitas Sumatera Utara, Medan, Indonesia3
Corresponding author: 2,3*
Keywords: ABSTRACT
platelet-lymphocyte ratio, Fournier gangrene severity index. Fournier gangrene, prognostics
Due to high mortality rates of Fournier Gangrene (FG), this type of gangrene appears to be a potentially fatal disease and has been included as emergency cases in urology. Recent studies have used several methods to estimate the FG patients' prognosis, including the Fournier Gangrene Severity Index (FGSI) and Platelet-Lymphocyte Ratio (PLR) methods. A descriptive study with a cross-sectional approach using secondary data from the medical records (2017-2021 data) of the Department of Surgery, Urology Division, Haji Adam Malik General Hospital Medan, was carried out (approved by the Research Ethics LP Committee). A higher FGSI score (>5.5) was determined, implying to a risk of a Fournier gangrene condition with a sensitivity and specificity of 60% and 60%, respectively, and a positive predictive value of 42.85%.
Higher PLR results (> 228.04) which was found from the records are potentially to be used as a prognostic factor to determine the outcome of a Fournier gangrene condition with a pretty good sensitivity and specificity of 90.00% and 90.00%, respectively as well as a predictive value positive of 81.81%. FGSI and PLR can be used as prognostic factors for cases of Fournier Gangrene.
This work is licensed under a Creative Commons Attribution Non-Commercial 4.0 International License.
1. Introduction
Fournier's Gangrene (FG) is a relatively rare disease, with an incidence rate up to 2 cases in 100,000 male patients with a case fatality rate of 7.5% [1]. Also, FG is a severe and life-threatening disease characterized by necrotic fascia in the perianal and genitourinary regions. Several factors, such as perianal disease, urethral stricture, local trauma, diabetes mellitus, and malignancy, are the reasons behind its development (FG infection) [2]. FG is classified as a potentially fatal disease with a high mortality rate and is included in
8522 emergency cases in urology. A study in America conducted retrospectively in 2017, 54 patients have been reported to be treated with a diagnosis of FG at LAC + USC Medical Center from 2010-2016. The FG infection occurs in polymicrobial, a combination of aerobic and anaerobic bacteria, and it is a progressive necrotizing fasciitis in the penis, scrotum, and perineum. Contrary to earlier description s, the disease is not restricted to young people or men, and its causes are now commonly identifiable [3]. Therefore, early and aggressive intervention is essential, as this condition is associated with high morbidity and mortality rates [4].
Recent studies have used several methods to estimate patient prognosis, including the Fournier Gangrene Severity Index (FGSI) and Platelet-Lymphocyte Ratio (PLR) methods. FGSI is a quantitative method used as a prognostic parameter in FG patients. The FGSI was assessed on the admission day, and the nine parameters of assessment were used to calculate scores of temperature, heart rate, respiratory rate, serum sodium, potassium, creatinine, bicarbonate, hematocrit, and white blood cell count. This score is divided into high level (>9) and low level (≤9) scores. Meanwhile, the PLR is an examination routinely carried out by taking blood samples from the periphery, thus; it is relatively accessible and inexpensive. Therefore, the parameters of PLR test-results can be used as an ideal biomarker to predict the outcome of patients with FG.
The PLR value will be higher in patients who require more than one debridement than in those who undergo only one debridement. As FG causes tissue necrosis which can be characterized by the changes of PLR, a high PLR (>140) could be a prognostic factor that is also useful for assessing the mortality of FG patients. This study aims to assess the role of FGSI and PLR as prognostic factors in patients diagnosed with at H. Adam Malik General Hospital, Medan.
2. Methods
This research is a descriptive study with a cross-sectional approach using secondary data from the medical records of the Department of Surgery, Urology Division, Haji Adam Malik General Hospital Medan (HAM Hospital). This research was conducted at HAM Hospital in Medan after being approved by the Research Ethics Committee with registration number 940/KEPK/USU/2022. In this study, the population was all patients at HAM Hospital who were diagnosed with Fournier Gangrene (FG) recorded from 01 January 2017 to 31 December 2021. The inclusion criteria for this study were; 1. Patients diagnosed with FG in the emergency room at HAM Hospital for January 1, 2017, to December 31, 2021; 2. Complete medical record data, including patient identity, vital signs, and laboratory examinations. The exclusion criteria for this study were; 1. FG patients with myocardial infarction; 2. FG patients diagnosed with other infections; 3.
Data from laboratory tests and incomplete vital signs. The data obtained were then statically analyzed using the Receiving Operator Curve (ROC) to determine the cut-off value of the PLR and FGSI scoring. The Area Under the Curve (AUC) was determined to demonstrate optimal values based on sensitivity and 1- specificity. The cut-off value obtained is then used as a predictive value for mortality.
This manuscript is prepared according to the STARD checklist for diagnostic/prognostic accuracy study [5].
3. Results
Medical records of sixty patients were sampled in this study. All patients are males in which 20 (33.33%) patients with Fournier's Gangrene (FG) mortality were found. A description on the demographical profiles of the data samples is stated in Table 1.
This study found that the mean age of the surviving group was 52.50 (±10.78) years, while that of the deceased group was 51.40 (±13.77) years. For the length of stay, the average length of stay in the deceased
8523 group was 10.71 (± 6.41) days, and in the group that survived, the length of stay was 11.20 (± 4.54) days.
The majority of samples were married in both groups, with comorbid urinary tract infections found in both groups. Based on the FGSI variable data, the platelet and lymphocyte values in Table 2 are noticeably distinguished in terms of the outcomes between those who were survived and deceased.
Based on statistical analysis on the patient characteristics between the survived and deceased groups, there was a statistical difference. According to the temperature characteristic, the mean in the survived group was 37.29 (± 0.84), while in the deceased group was 36.96 (± 0.83) with a p-value of 0.019. Next is the variable pulse and respiratory rates sequentially; the mean values were 92.63 (± 8.31) and 93.24 (± 12.27); 21.00 (±
2.33) and 20.36 (± 2.04), respectively for the survived and deceased groups. Moreover, the respective p- values were 0.067 and 0.066. For the serum sodium levels, the mean in survived patients was 131.00 (±
6.75), and in the deceased group was 129.08 (± 4.98) with a p-value = 0.009.
Based on the serum potassium variable, the mean creatinine serum levels in the survived patients and deceased patients were 1.14 (±0.47) and 1.64 (±1.33), respectively, with a p-value = 0.454. Next is the serum hematocrit, where the mean value in survived patients is 31.94 (±6.52) and the value in deceased patients was 30.36 (±5.30); a statistically significant difference was found with p = 0.065. Two other variables assessed in this study were serum white-blood cells and serum bicarbonate. For the leukocyte serum values, respectively, accounted for the survived and the deceased groups were 14,898.29 (±6,167.92) and 17,660.80 (± 14,009.69); a statistically significant difference was obtained with p-value = 0.045. In the serum bicarbonate variable, the survived group had an average of 16.90 (± 4.96) and the deceased group was 14.88 (± 3.52) with p=0.032. For platelet values, respectively between the survived and deceased groups were 289.05(±119.709) and 334.680(±128.614) with obtained p value = 0.013. In lymphocyte variables, This study evaluated the comparison of the Fournier’s Gangrene Severity Index (FGSI) and Platelets Lymphocyte Ratio (PLR) values on the mortality risks. The FGSI and PLR values can be seen in Table 3.
Based on Table 3, the mean value of the FGSI was 6.27 with the lowest value from 2 to the highest being 15, while the mean PLR was 216.32 with the lowest value being 45 and the highest being 810.
Based on Figure 1, the area of the PLR curve was larger than that of the FGSI curve. The ROC of PLR curve also showed an intersection point of 0.951, and the FGSI curve showed an intersection point at 0.729.
There was a significant association between the FGSI score and the cut-off value of 5.5 with the grouping of FGSI values <5.5 to >5.5. There were 16 patients who survived and 12 patients who died in the group with a score > 5.5. Whilst, in the group with a score of <5.5, there were 24 patients who survived and 8 patients who died. Statistical analysis showed a significance with a p value of 0.176. For the PLR score, a cut-off value of 228.04 was obtained with a grouping of > 228.04 to < 228.04, and there were 4 patients who survived with a PLR score of > 228.04 (18 patients were deceased). In the PLR score of <228.04, 36 patients survived while 2 patients were deceased. Statistical analysis also showed significance with a p value of 0.0001.
From the data, for the FGSI scoring, a cut-off that was > 5.5 with a sensitivity value of 60.00% and a specificity value of 60.00% were obtained. In the PLR scoring, we obtained a cut-off of >228.04 and a higher sensitivity value than the FGSI score, namely 90.00% and a specificity value of 90.00%.
Figure 2 illustrates the PLR and FGSI scores as prognostic factors in FG patients at HAM Hospital for the
8524 period 2017-2021 on the Pearson correlation test results with a strong correlation (r = 0.669).
4. Discussions
This study found that the mean age of the patients in the survived group was 52.50 (±10.78) years, while those of the deceased group was 51.40 (±13.77) years. Most of the sample were married in both groups (70.6% and 22.4%), with comorbid urinary tract infections (UTI) found in both groups. Several previous studies have found an average that is quite similar to this study. In the [6], the average age of the sample was 53.13 ± 15.36 years.
Similar results were obtained in the Uzunoglu study in Turkey in 2019 with an average age of 53.38 ± 11.94 years in the survived group and 53.11 ± 11.61 years in the deceased group [7]. Another report by Aridogan, the average age value was reported to be 61.3 years, varying from 36 to 92 years. From several of these studies, the ages of patients with Fournier's Gangrene (FG) appear to distribute widely, ranging from 20 years to 92 years of age [8]. Several risk factors that are associated with FG are diabetes mellitus, alcohol consumption, hypertension, smoking,
The duration of treatment is another variable assessed in this study. In the deceased group, the mean of treatment duration was 10.71 (± 6.41) days, and in the survived group was 11.20 (± 4.54) days. Previous studies have shown varying results, i.e., [6] reported the average length of stay in survived patients was 21.02 ± 14.79 days and in deceased patients was 6.78 ± 6.71 days. Another finding has also reported that the survived patients were treated for 28 days, while deceased patients were 8 days (Essay, 2007). Unalp and co-workers reported the length of stay in survived patients was longer (31.54 days) than those in the deceased group (12.8 days) [9]. Another study reported that the length of stay of patients who lived was 29.6 days compared to 6 in the deceased group [10].
Other parameters assessed from the FGSI score is serum bicarbonate. In our study, the bicarbonate levels of survived patients were 21.19 (±2.55) mEq/L compared to those in deceased group, 18.87 (± 4.14) mEq/L with a value of p=0.032. In contrast, Lin's findings in 2014 and 2019 statistically determined the p = 0.410 and p = 0.732 [11], [12].
In the assessment of neutrophils between the group that survived and the group that were deceased were 81.39 (±11.075) and 91.82 (±12.24) respectively, also; the obtained p- p = 0.013 which was statistically significant. In the lymphocyte variable, the survived group had an average of 11.18(±4.80) and the deceased group was 8.57(±2.92) with a p=0.508. In Pehlivanli's 2018 study, there was no statistically significant difference in neutrophil monitoring with a p-value = 0.062, but there was a significant difference in lymphocyte monitoring with a p = 0.016 [13].
Several previous studies have attempted to utilize FGSI as a pre-determined methods to evaluate the mortality risks in FG patients. Most studies have confirmed a cut-off value of > 9 with sensitivity and specificity values ranging from 71-88% and 78-90%, respectively [14- 16]. Meanwhile, in a study conducted by [17], it had a cut-off value of > 10 and obtained a sensitivity and specificity value of 65% and 100%, respectively. Another study from [18] obtained a cut-off value of > 3 and obtained a sensitivity of 77% and a specificity of 70%. There was a significant association between the FGSI score and the cut-off value of 5.5 with the grouping of FGSI values <5.5 to >5.5. Furthermore, there were 16 patients who survived, while 12 patients who died in the group with a score > 5.5. In the group with a score of <5.5, there were 24 patients in the survived group and 8 patients in the deceased groups, with statistical analysis of p value = 0.176.
8525 In Bozkurt's 2014 study, a significant difference was found between the FGSI cut-off values ≥4 and the FGSI mortality incidences (p <0.01), and a sensitivity of 66.7% and a specificity of 86.7% were confirmed [19]. Mehmet's study in FGSI and the prognosis of mortality cases with a cut-off value of ≥4 demonstrated an average FGSI value of 7 (4.25–9.25) in deceased patients and 2 (1–4) in survived patients with a value of p=0.013 (with a total sample of 60 patients consisted of 50 survived patients and 10 deceased patients) [20].
Another study also has reported a difference in FGSI values in survived patients with a value of 6.78 ± 2.49, while in the deceased group, a value of 14.40 ± 2.19 was found with a p-value <0.001; there was a significant difference [13].
For the PLR score, a cut-off value of 228.04 was obtained with a grouping of > 228.04 to < 228.04. There were 4 patients who survived with a PLR score of > 228.04 whereas at a PLR score of <228.04, there were 36 patients who survived. Statistical analysis showed significance with a p value of 0.0001. In Pehlivanli's study, the average PLR value in the survived patients was 6.95 ± 6.31 and in deceased patients, the value was 22.30 ± 30.31 with a p = 0.003 which was statistically significant [13]. Bozkurt and co-workers also obtained significant results when comparing PLR ≥10 and PLR <10 to the mortality prognosis, and they found a statistically significant difference (p <0.05) between these two PLR groups [19]. Moreover, significant differences were also found in terms of the need for intensive care and duration of stay [19]. [6], have also obtained PLR sensitivity and specificity values of 70.73% and 70.37% which were statistically significant for mortality (p=0.002), determined via cut-off value of 8.595. The PLR values of patients who were deceased according to Uzunoglu's study were significantly higher than those who were alive; even though observations were performed at different times (when the patient first entered the hospital (p = 0.002) and during treatments (p = 0.002). 002) when using a cut-off value of 8,595 [6]. The PLR values of patients who died according to Uzunoglu's study were significantly higher than patients who were alive even though observations were made at different times, namely when the patient first entered the hospital (p
= 0.002) and during treatment (p = 0.002) [7].
Several scoring systems have been developed to determine the severity of FG as well as to predict the morbidity/death. One of the scoring systems that have been considered to have a potential is the FGSI score.
This system is well-known when it was first introduced. However, several studies have reported that this scale is not statistically significant. With no analysis between the association of the onset of Fournier's disease and the gangrene infection (in the arrival time to the emergency room) limits the predictive value.
Another limitation is that there is no observation of comorbidities that might affect the patient's prognosis as well as the administration of certain drugs; in which in this study may contribute particularly in the inflammatory and healing processes among patients with FG.
5. Conclusions
A higher score of Fournier Gangrene Severity Index (FGSI - > 5.5) is the potential to be used as a prognostic factor in determining the outcome of a Fournier’s Gangrene (FG) condition with an equal sensitivity and specificity of 60%; a positive predictive value of 42.85%. Higher Platelets-to-Lymphocyte Ratio (PLR) results (> 228.04) can be an indication of a prognostic factor for determining FG condition with acceptable sensitivity and specificity (90% equally) with a positive predictive value of 81.81%. The FGSI demonstrated to be a positive predictive value (42.85%) which was lower than the PLR ratio (81.81%).
Ethical clearance
This study was approved by the Research Ethics Committee with registration number 940/KEPK/USU/2022 and was conducted according Helsinki Declaration. Informed consent was approved
8526 by all study subjects and a proper explanation was given to the patient.
Acknowledgements
The authors would like to thank everyone who supported this study. Special thanks are given to Adam Malik general hospital and Universitas Sumatera Utara which fully supported the authors during writing period.
Author Contributions
Study concept and design: Syah Mirsya Warli, Batara Joseph Sihotang Data acquisition: Batara Joseph Sihotang
Data analysis: Batara Joseph Sihotang, Dhirajaya Dharma Kadar Drafting of manuscript: Batara Joseph Sihotang
Critical revision of the manuscript: Batara Joseph Sihotang, Syah Mirsya Warli, Dhirajaya Dharma Kadar Conflicts of Interest
The authors declare no conflict of interest.
Funding None.
6. References
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Table 1. Demographic Characteristics
Characteristics Survived (n=40) Deceased (n=20)
Age (years) (mean±SD) 52.50 (± 10.78) 51.40 (±13.77)
8528 Length of Treatment (days) (mean±SD) 11.20 (±4.54) 10.71 (±6.41)
Employment (n, %)
Civil servant 6 (15%) 4 (20%)
Farmer 8 (20%) 6 (30%)
Laborer 9 (22.5%) 3 (15%)
Employee 6 (15%) 5 (25%)
Self-employed 11 (27.5%) 2 (10%)
Education (n,%)
Elementary school 0 (0%) 3 (15%)
Junior High School 8 (20%) 4 (20%)
Senior High School 25 (62.5%) 10 (50%)
University 7 (17.5%) 3 (15%)
Marriage History (n, %)
Yes 36 (90%) 15 (75%)
Not 4 (10%) 5 (25%)
History of Urinary Tract Infection (n, %)
Yes 10 (25%) 8 (40%)
Not 30 (75%) 12 (60%)
Table 2. Characteristics of Survived and Deceased Patients
Characteristics Survived Deceased p-value
Temperature (°C) 37.29 (±0.84) 36.96 (± 0.83) 0.019a
Pulse rate (x/minute) 92.63 (± 8.31) 93.24 (±12.27) 0.067a Respiratory rate (x/min) 21.00 (± 2.33) 20.36 (± 2.04) 0.066a Serum Sodium (mmol/L) 131.00 (± 6.75) 129.08 (±4.98) 0.009a Serum Potassium (mmol/L) 3.61 (±0.44) 4.03 (±0.91) 0.495a
Serum Creatinine (mg/dL) 1.14 (±0.47) 1.64 (±1.33) 0.018b
Serum Hematocrit (%) 31.94 (±6.52) 30.36 (±5.30) 0.065b
Leukocyte Serum (/mm3) 14,898.29 (±6,167.92)
17,660.80 (± 14,009.69)
0.045a
Serum Bicarbonate(mEq/L) 16.90 (± 4.96) 14.88 (± 3.52) 0.041a
Platelets 289.05(±119.709) 334,680(±128,614) 0.013a
Lymphocytes 14.59(±4.12) 8.61 (±4.55) 0.508a
aBy independent T-test (p-value <0.05 is considered significant)
bBy Mann-Whitney test (p-value <0.05 is considered significant)
Table 3. FGSI and PLR mean values
8529
Characteristics Mean (Min-Max)
FGI 6.27 (2-15)
PLR 216.32 (45-810)
Table 4. FGSI and PLR Mean Scores based on mortality
Variable Life
Mean(±SD)
Die
Mean(±SD)
FGI score 5.00 (± 2.00) 8.00 (± 4.00)
PLR score 142.00 (± 47.00) 320.00 (± 142.00)
Table 5. Association between FGSI and Mortality
Variable Deceased Survived Total p-values
FGSI score > 5.5 12 16 28 0.176
FGSI score < 5.5 8 24 32
Total 20 40 60
FGI sensitivity :60% FGSI Specificity: 60%
PPV FGSI :42.85% NPV FGSI :75%
Table 6. Association of PLR and Mortality
Variable Deceased Survived Total p-values
PLR score > 228.04 18 4 22 0.0001
PLR score < 228.04 2 36 38
Total 20 40 58
PLR sensitivity :90.00% PLR Specificity: 90.00%
PPV PLR :81.81% PLR NPV: 94.00%
8530 Figure 1. ROC curves for FGSI and PLR on mortality
Figure 2. FGI and PLR Scatter Diagrams
