Lymphocyte and Neutrophil to Lymphocyte Ratio do not Predict Mortality in Hip Fracture Patients

DAN VASILE POP1, CRISTINA VLAD DALIBORCA2*, DANIELA RADU3, DINU VERMESAN1, BOGDAN DELEANU1, AHMED ABU AWWAD1, ADRIAN TODOR4 1Victor Babes University of Medicine and Pharmacy, Department of Orthopedics and Trauma, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 2Victor Babes University of Medicine and Pharmacy, Department of Pharmacology, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 3Victor Babes University of Medicine and Pharmacy, Department of Surgery, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania 4Iuliu Hatieganu University of Medicine and Pharmacy, Department of Orthopedics, Traumatology and Pediatric Orthopedics, 8 Victor Babes Str.,400012, Cluj Napoca, Romania

Our study aimed to assess whether admission hemoglobin, lymphocyte count and neutrophil to lymphocyte ratio (N/R) can predict 1-year survival in patients with hip fractures. In the study, data from 54 patients with femoral neck fractures, 119 with trochanteric fractures respectively 24 with subtrochanteric fractures was analyzed. All the included patients were older than 55 years and were followed up to 2 years or until the decease occurred. The following parameters were recorded in patients with femoral neck, trochanteric respectively subtrochanteric fractures: average age: 76; 79.7 respectively 73.3 years; male to female ratio: 1:2.86; 1:3.1 respectively 1:2; average hemoglobin at admission: 13.13, 11.56 respectively 11.81; average lymphocyte count: 1.69; 1.7 respectively 1.75. At the logistic regression model built having the death as outcome and the lymphocytes respectively the N/L as predictors, we did notfound any significant associations in neither of the groups (p values of 0.837, 0.171 and 0.162 for lymphocyte and 0.920, 0.764 and 0.168 for N/ L respectively). When age, gender and hemoglobin at admittance were accounted for, only for fractures of the trochanteric region age was predictive of survival with p<0.001. Our study showed no prediction for survival of hip fracture patients by using perioperatively collected total lymphocyte count and neutrophil to lymphocyte ratio. Keywords: hip fracture; femoral neck; survival; lymphocyte; neutrophil to lymphocyte ratio Hip fractures are a major social and healthcare burden. They occur in elderly frail population and have high mortality [1,2].
Several factors have been shown to be predictive of outcome, such as age, male gender, extracapsular fracture, delay of surgery, comorbidities and nutritional status. Routine blood tests are readily available for preoperative planning and have been shown to be predictive for cancer and cardiovascular events outcome [3,4].
In hip fracture patients there is some evidence that several simple laboratory markers could predict survival [5,6].
We aimed to determine whether admission hemoglobin, lymphocyte count and neutrophil to lymphocyte ratio can predict 1-year survival after hip fracture patients.

Experimental part
We performed a retrospective, single center observational study of with prospectively collected data for survival. Hip fracture patients over 55 years old admitted for surgical treatment over 9 months (Oct.2015 to Jun.2016) were scrutinized. Electronic charts were subsequently reviewed by two authors. 197 patients were included for analysis. Those who did not undergo surgical treatment, had total arthroplasty or extramedullary fixation were excluded. Age, gender, hemoglobin, neutrophil and lymphocyte at admittance and type of surgical treatment were recorded in Excel (Microsoft Office 10). Hematology panel was determined using ADVIA 2120 flow cytometry and spectrophotometry. Patients were then prospectively followed up until Oct.2017 (1.25-2 years) when survival status was retrieved. The study was approved by the Hospital's Ethics Committee and Research department.
To assess the association between the studied parameters and the risk of death, we built logistic regression models in which the outcome was considered the death event, while the different parameters from the study were considered possible predictors.

Results and discussions
We included 54 femoral neck fractures, 119 fractures of the trochanteric region and 24 subtrochanteric. The displaced femoral neck fractures were treated using press fit hemiarthroplasty (Biomet, Warsaw, USA) through a lateral approach. For extracapsular fractures internal fixation was performed using standard or long Gamma3 nails (Stryker, USA). Surgical techniques adhered to the manufacturer's recommendations and were performed under regional anesthesia (spinal, epidural or combined spinal-epidural). Comparative demographic data is presented in table 1.
Influence of lymphocyte and neutrophil to lymphocyte ratio (N/L) was determined in each of the 3 groups as well as overall. For the femoral neck fractures, fractures of the trochanteric and subtrochanteric region respectively, the associations from the logistic regression model proved to be not significant, with p values of 0.837, 0.181 and 0.162 for lymphocyte and 0.920, 0.794 and 0.168 for N/L respectively (Table 2). When age, gender and hemoglobin at admittance were accounted for, only for the fractures of the trochanteric region age was an independent predictor of survival with p<0.001.
In our study, the absolute lymphocyte number as well as N/L were not predictive of survival up to 2 years after surgical treatment of a proximal hip fracture. In addition, neither was hemoglobin at admittance nor male gender. Age was only significant for the subgroup of trochanteric fractures.
These findings differ from some of our previous analysis on survival, as well as other data from the literature [1,5,6].
This might account for the differences in results as well as underline what we consider to be the main weakness of our study. Discrepancies between several studies in the literature are also noted regarding the predictive weight each parameter has.
Mosfeldt et al found a much higher influence of serum creatinine on survival; in their study, mortality in patients with elevated levels of creatinine was three times higher compared with those with values in the normal range. Mortality was also associated with age, low hemoglobin, high plasma potassium, and low plasma albumin levels [9].
Hip fracture patients are generally addressed as subgroup populations. However, treatment may sometimes require adjustment from the norms is peculiar cases such as amputations or malignancy [1,10,12].
The ability to obtain prediction of outcome and adverse events from simple, readily available lab values is very tempting. Unlike specialized tests, standard blood count and routine biochemistry are performed for preoperative planning and general assessment [5,11,13,14].
Lymphocyte count is regarded as a marker for energetic malnutrition whereas the neutrophil to lymphocyte ratio is a marker of inflammation [5,6,15].
There might be some value for the N/L ratio in knee arthroplasty for osteoarthritis (OA). N/L ≥2.1 emerged as independent predictor indicating severity of knee OA [16].
It has a faster normalization than CRP (C-reactive protein) and thus could represent a potentially better biomarker to follow post-operative inflammation or early infection after total knee replacement [17].
In addition, other factors also contribute to successful treatment of hip fractures. Large sample research and use of standardized outcome measures such as patient reported outcomes may bring a better way of assessing and predicting postoperative follow up [21,23].

Conclusions
Our study showed no prediction for survival of hip fracture patients by using perioperatively collected total lymphocyte count and neutrophil to lymphocyte ratio.