# Sterile Inflammatory Response and Surgery-Related Trauma in Elderly Patients with Subtrochanteric Fractures

## Abstract

**:**

## 1. Introduction

^{+}in the extracellular matrix [13]. Monocytes have high infiltrative properties that can aid the removal pathogen-associated molecular patterns (PAMPs) and cellular debris through phagocytosis [14]. Lymphocytopenia can predict mortality and was associated with major postoperative complications in multiple studies [15,16,17].

## 2. Materials and Methods

#### 2.1. Study Design and Participants

#### 2.2. Data Acquisition

#### 2.3. Hematologic Derived Markers of Inflammation

- $\mathrm{NLR}=\frac{\mathrm{N}\mathrm{e}\mathrm{u}\mathrm{t}\mathrm{r}\mathrm{o}\mathrm{p}\mathrm{h}\mathrm{i}\mathrm{l}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}{\mathrm{L}\mathrm{y}\mathrm{m}\mathrm{p}\mathrm{h}\mathrm{o}\mathrm{c}\mathrm{y}\mathrm{t}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}$
- $\mathrm{P}\mathrm{L}\mathrm{R}=\frac{\mathrm{P}\mathrm{l}\mathrm{a}\mathrm{t}\mathrm{e}\mathrm{l}\mathrm{e}\mathrm{t}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}{\mathrm{L}\mathrm{y}\mathrm{m}\mathrm{p}\mathrm{h}\mathrm{o}\mathrm{c}\mathrm{y}\mathrm{t}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}$
- $\mathrm{M}\mathrm{L}\mathrm{R}=\frac{\mathrm{M}\mathrm{o}\mathrm{n}\mathrm{o}\mathrm{c}\mathrm{y}\mathrm{t}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}{\mathrm{L}\mathrm{y}\mathrm{m}\mathrm{p}\mathrm{h}\mathrm{o}\mathrm{c}\mathrm{y}\mathrm{t}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}$

- 4.
- $\mathrm{S}\mathrm{I}\mathrm{I}=\frac{\mathrm{N}\mathrm{e}\mathrm{u}\mathrm{t}\mathrm{r}\mathrm{o}\mathrm{p}\mathrm{h}\mathrm{i}\mathrm{l}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}\text{}\times \text{}\mathrm{P}\mathrm{l}\mathrm{a}\mathrm{t}\mathrm{e}\mathrm{l}\mathrm{e}\mathrm{t}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}{\mathrm{L}\mathrm{y}\mathrm{m}\mathrm{p}\mathrm{h}\mathrm{o}\mathrm{c}\mathrm{y}\mathrm{t}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}$
- 5.
- $\mathrm{S}\mathrm{I}\mathrm{R}\mathrm{I}=\frac{\mathrm{M}\mathrm{o}\mathrm{n}\mathrm{o}\mathrm{c}\mathrm{y}\mathrm{t}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}\text{}\times \text{}\mathrm{P}\mathrm{l}\mathrm{a}\mathrm{t}\mathrm{e}\mathrm{l}\mathrm{e}\mathrm{t}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}{\mathrm{L}\mathrm{y}\mathrm{m}\mathrm{p}\mathrm{h}\mathrm{o}\mathrm{c}\mathrm{y}\mathrm{t}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}$
- 6.
- $\mathrm{A}\mathrm{I}\mathrm{S}\mathrm{I}=\frac{\mathrm{N}\mathrm{e}\mathrm{u}\mathrm{t}\mathrm{r}\mathrm{o}\mathrm{p}\mathrm{h}\mathrm{i}\mathrm{l}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}\text{}\times \text{}\mathrm{M}\mathrm{o}\mathrm{n}\mathrm{o}\mathrm{c}\mathrm{y}\mathrm{t}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}\text{}\times \text{}\mathrm{P}\mathrm{l}\mathrm{a}\mathrm{t}\mathrm{e}\mathrm{l}\mathrm{e}\mathrm{t}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}{\mathrm{L}\mathrm{y}\mathrm{m}\mathrm{p}\mathrm{h}\mathrm{o}\mathrm{c}\mathrm{y}\mathrm{t}\mathrm{e}\text{}\mathrm{c}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}}$

#### 2.4. Surgical Procedure

#### 2.5. Statistical Analysis

## 3. Results

^{2}= 4.564, p = 0.813, and Nagelkerke R

^{2}= 0.754). The intrinsic immune response triggered by the invasiveness of the surgical technique was suggestive as a whole through the values obtained in the proposed equation: NLR (OR 2.91, 95% CI 1.28–6.61, p < 0.0001), PLR (OR 1.59, 95% CI 1.34–1.88, p = 0.003), MLR (OR 1.45, 95% CI 1.18–1.78, p = 0.005), SII (OR 1.02, 95% CI 1.001–1.03, p = 0.039), SIRI (OR 1.04, 95% CI 1.01–1.07, p = 0.028), and AISI (OR 1.25, 95% CI 1.05–1.49, p = 0.020).

## 4. Discussion

## 5. Conclusions

## Funding

## Institutional Review Board Statement

## Informed Consent Statement

## Data Availability Statement

## Acknowledgments

## Conflicts of Interest

## References

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**Figure 2.**An 84-year-old patient diagnosed with a subtrochanteric fracture after a fall from the same height treated with CRIF with long Gamma Nail fixation: (

**a**) preoperative radiograph; (

**b**,

**c**) postoperative radiographs.

**Figure 3.**ROC curve representations for open versus closed reduced STFs, concerning: (

**a**) inflammatory markers at admission; (

**b**) surgical factors (days to surgery, duration of surgery, and length of hospital stay); and (

**c**) inflammatory markers on the first day after surgery.

**Figure 4.**Closed versus open reduction groups boxplots at admission and on the first postoperative day: (

**a**) the neutrophil-lymphocyte ratio; (

**b**) platelet–lymphocyte ratio; (

**c**) monocyte–lymphocyte ratio; (

**d**) systemic inflammation index; (

**e**) systemic inflammation response index; (

**f**) aggregate inflammation systemic index. Circles represent the mild outliers and asterisks represent the extreme outliers.

**Table 1.**Optimal cut-off values, AUC, and the accuracy prediction identified by the ROC curve analysis.

Variables | Cut-Off Values | AUC | 95% CI | Sensitivity | Specificity | p-Value |
---|---|---|---|---|---|---|

NLR—Admission | 6.57 | 0.421 | 0.322–0.520 | 31% | 65.9% | 0.109 |

PLR—Admission | 156.76 | 0.451 | 0.354–0.548 | 46.6% | 54.1% | 0.325 |

MLR—Admission | 0.54 | 0.561 | 0.466–0.657 | 55.2% | 58.8% | 0.214 |

SII—Admission | 1353.31 | 0.409 | 0.313–0.505 | 34.5% | 56.5% | 0.065 |

SIRI—Admission | 91.83 | 0.514 | 0.419–0.610 | 62.1% | 47.1% | 0.774 |

AISI—Admission | 834.86 | 0.456 | 0.361–0.552 | 44.8% | 0.51% | 0.377 |

NLR—Postoperative | 6.95 | 0.026 | 0.844–0.947 | 94.8% | 70.6% | <0.0001 |

PLR—Postoperative | 186.13 | 0.039 | 0.698–0.851 | 79.3% | 65.9% | <0.0001 |

MLR—Postoperative | 0.66 | 0.034 | 0.755–0.889 | 89.7% | 61.2% | <0.0001 |

SII—Postoperative | 1970.47 | 0.026 | 0.846–0.947 | 86.2% | 81.2% | <0.0001 |

SIRI—Postoperative | 167.54 | 0.032 | 0.781–0.906 | 87.9% | 68.2% | <0.0001 |

AISI—Postoperative | 1857.45 | 0.025 | 0.849–0.948 | 82.8% | 85.9% | <0.0001 |

Days to days | 2 | 0.049 | 0.509–0.699 | 60.3% | 56.5% | 0.035 |

Duration of surgery (minutes) | 58 | 0.025 | 0.855–0.951 | 82.8% | 83.5% | <0.0001 |

Length of hospital stay (days) | 8 | 0.044 | 0.610–0.783 | 65.5% | 58.8% | <0.0001 |

Variable | All Patients (n = 143) | Closed Reduction Group (n = 85) | Open Reduction Group (n = 58) | p-Value |
---|---|---|---|---|

Baseline characteristics | ||||

Age (years), mean ± SD | 73.71 ± 14.34 | 73.27 ± 14.30 | 74.34 ± 14.49 | 0.662 |

Sex, n (%) Male Female | 55 (38.5) 88 (61.5) | 31 (36.5) 54 (63.5) | 24 (41.4) 34 (58.6) | 0.554 |

Alcohol (yes), n (%) | 34 (23.8) | 20 (23.5) | 14 (24.1) | 0.933 |

Smoking (yes), n (%) | 35 (24.5) | 23 (27.1) | 12 (20.7) | 0.384 |

Obesity (yes), n (%) | 73 (51.0) | 40 (47.1) | 33 (56.9) | 0.248 |

Living area, n (%) Rural Urban | 72 (50.3) 71 (49.7) | 41 (48.2) 44 (51.8) | 31 (53.4) 27 (46.6) | 0.540 |

SD (yes), n (%) | 18 (12.6) | 10 (11.8) | 8 (13.8) | 0.918 |

EH (yes), n (%) | 95 (66.4) | 57 (67.1) | 38 (65.5) | 0.848 |

AF (yes), n (%) | 26 (18.2) | 13 (15.3) | 13 (22.4) | 0.278 |

CIHD (yes), n (%) | 78 (54.8) | 43 (50.6) | 35 (60.3) | 0.250 |

PVI (yes), n (%) | 42 (29.4) | 20 (23.5) | 22 (37.9) | 0.063 |

PF (yes), n (%) | 22 (15.4) | 13 (15.3) | 9 (15.9) | 0.971 |

COPD (yes), n (%) | 38 (26.6) | 19 (22.4) | 19 (32.8) | 0.167 |

Dyslipidemia (yes), n (%) | 46 (32.2) | 30 (35.3) | 16 (27.6) | 0.333 |

Diabetes (yes), n (%) | 26 (18.2) | 17 (20.0) | 9 (15.5) | 0.495 |

Surgical factors | ||||

Side of the fracture, n (%) Left Right | 58 (40.6) 85 (59.4) | 34 (40.0) 51 (60.0) | 24 (41.4) 34 (58.6) | 0.869 |

ASA score, n (%) ˂III ≥III | 49 (34.3) 94 (65.7) | 30 (35.3) 55 (64.7) | 19 (32.8) 39 (67.2) | 0.754 |

Type of anesthesia, n (%) Spinal General | 92 (64.3) 51 (35.7) | 56 (65.9) 29 (34.1) | 36 (62.1) 22 (37.9) | 0.640 |

Days to surgery, 0–2 cut-off >2 | 71 (49.7) 72 (50.3) | 48 (56.5) 37 (43.5) | 23 (39.7) 35 (60.3) | 0.048 |

LOHS (days), 0–8 cut-off >8 | 70 (49.0) 73 (51.0) | 50 (58.8) 35 (41.2) | 20 (34.5) 38 (65.5) | 0.004 |

Duration of surgery (min), 0–58 cut-off >58 | 81 (56.6) 62 (43.4) | 71 (83.5) 14 (16.5) | 10 (17.2) 48 (82.8) | <0.0001 |

Laboratory data at admission | ||||

Neutrophil count (×10^{3}/µL),median (IQR) | 6.99 (4.20) | 7.89 (4.32) | 6.77 (3.63) | 0.059 |

Lymphocyte count (×10^{3}/µL),median (IQR) | 1.38 (0.88) | 1.33 (0.75) | 1.45 (1.04) | 0.528 |

Monocyte count (×10^{3}/µL),median (IQR) | 0.71 (0.39) | 0.70 (0.30) | 0.73 (0.40) | 0.177 |

PLT count (×10^{3}/µL),median (IQR) | 212 (94) | 224 (98) | 202 (80) | 0.068 |

AST/ALT (>1, reference), median (IQR) | 1.44 (0.59) | 1.45 (0.61) | 1.36 (0.59) | 0.710 |

WBC (×10^{3}/µL), median (IQR) | 10.20 (4.20) | 10.39 (4.53) | 9.90 (3.41) | 0.335 |

RBC (×10^{6}/µL), median (IQR) | 3.91 (1.26) | 4.02 (1.22) | 3.68 (1.06) | 0.123 |

HGB (g/dL), median (IQR) | 11.90 (3.38) | 12.30 (3.20) | 11.60 (3.04) | 0.096 |

NLR (>6.57, cut-off), n (%) | 46 (32.2) | 29 (34.1) | 17 (29.3) | 0.546 |

PLR (>156.76, cut-off), n (%) | 66 (46.2) | 39 (45.9) | 27 (46.6) | 0.937 |

MLR (>0.54, cut-off), n (%) | 69 (49.3) | 37 (45.1) | 32 (55.2) | 0.241 |

SII (>1353.31, cut-off), n (%) | 57 (39.9) | 37 (43.5) | 20 (34.5) | 0.278 |

SIRI (>91.83, cut-off), n (%) | 81 (56.6) | 45 (52.9) | 36 (62.1) | 0.306 |

AISI (>834.86), n (%) | 67 (46.9) | 41 (48.2) | 26 (44.8) | 0.688 |

Laboratory data after surgery | ||||

Neutrophil count (×10^{3}/µL),median (IQR) | 9.08 (5.52) | 7.29 (4.35) | 11.67 (4.55) | <0.0001 |

Lymphocyte count (×10^{3}/µL),median (IQR) | 1.17 (0.67) | 1.36 (0.63) | 0.93 (0.50) | <0.0001 |

Monocyte count (×10^{3}/µL), mean ± SD | 0.92 ± 0.41 | 0.81 ± 0.36 | 1.07 ± 0.42 | <0.0001 |

PLT count (×10^{3}/µL)median (IQR) | 230 (96) | 224 (97) | 255.5 (70) | 0.008 |

WBC (×10^{3}/µL),median (IQR) | 10.01 (5.81) | 9.25 (4.14) | 11.80 (6.74) | <0.0001 |

RBC (×10^{6}/µL),median (IQR) | 2.98 (0.78) | 3.12 (0.83) | 2.82 (0.55) | 0.002 |

HGB (g/dL) mean ± SD | 9.27 ± 1.69 | 9.60 ± 1.64 | 8.78 ± 1.65 | 0.004 |

NLR (>6.95, cut-off), n (%) | 67 (46.9) | 18 (21.2) | 49 (84.5) | <0.0001 |

PLR (>186.13, cut-off), n (%) | 76 (53.1) | 30 (35.3) | 46 (79.3) | <0.0001 |

MLR (>0.66, cut-off), n (%) | 68 (48.2) | 27 (32.1) | 41 (71.9) | <0.0001 |

SII (>1970.47, cut-off), n (%) | 76 (53.1) | 22 (25.9) | 54 (93.1) | <0.0001 |

SIRI (>167.54, cut-off), n (%) | 78 (54.5) | 27 (31.8) | 51 (87.9) | <0.0001 |

AISI (>1857.45), n (%) | 60 (42.0) | 12 (14.1) | 48 (82.8) | <0.0001 |

Variable | Sterile Inflammation | p-Value | |
---|---|---|---|

OR | 95% CI | ||

NLR Postoperative | 2.91 | 1.28–6.61 | <0.0001 |

PLR Postoperative | 1.59 | 1.34–1.88 | 0.003 |

MLR Postoperative | 1.45 | 1.18–1.78 | 0.005 |

SII Postoperative | 1.02 | 1.001–1.03 | 0.039 |

SIRI Postoperative | 1.04 | 1.01–1.07 | 0.028 |

AISI Postoperative | 1.25 | 1.05–1.49 | 0.020 |

Days to surgery | 1.34 | 1.04–1.72 | 0.009 |

Duration of surgery (min) | 1.21 | 1.12–1.30 | 0.019 |

LOHS (days) | 1.34 | 1.10–1.64 | 0.011 |

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**MDPI and ACS Style**

Moldovan, F.
Sterile Inflammatory Response and Surgery-Related Trauma in Elderly Patients with Subtrochanteric Fractures. *Biomedicines* **2024**, *12*, 354.
https://doi.org/10.3390/biomedicines12020354

**AMA Style**

Moldovan F.
Sterile Inflammatory Response and Surgery-Related Trauma in Elderly Patients with Subtrochanteric Fractures. *Biomedicines*. 2024; 12(2):354.
https://doi.org/10.3390/biomedicines12020354

**Chicago/Turabian Style**

Moldovan, Flaviu.
2024. "Sterile Inflammatory Response and Surgery-Related Trauma in Elderly Patients with Subtrochanteric Fractures" *Biomedicines* 12, no. 2: 354.
https://doi.org/10.3390/biomedicines12020354