Evaluating the learning curve and outcomes of a new rectangular femoral stem in total hip arthroplasty: A comparative study

Abstract

Background

Total hip arthroplasty (THA) is a widely successful procedure, but the adoption of new femoral stems is often met with hesitation due to concerns regarding a learning curve and potential complications. This study evaluates the impact of introducing a new rectangular femoral stem by comparing radiographic, clinical, and functional outcomes with those of an established metaphyseal loading stem.

Methods

A retrospective comparative study was conducted between January 2022 and January 2024. Patients were categorized into three groups: (1) control group receiving an established metaphyseal loading stem, (2) “learning curve” group (first half of patients receiving the new rectangular stem), and (3) “experienced” group (second half of patients receiving the rectangular stem). Primary outcomes included femoral stem subsidence and diaphyseal canal filling. Secondary outcomes comprised Oxford Hip Scores (OHS), EQ-5D-5L scores, length of hospital stay, complications, and readmission rates. Statistical analysis utilized ANOVA and chi-square tests, with significance set at p < 0.05.

Results

A total of 115 patients (33 control, 41 learning curve, 41 experienced) were included. No significant differences were found in demographics. Subsidence was comparable across groups (p = 0.381). AP canal filling showed no significant differences (p = 0.839), but lateral canal filling was greater in the rectangular stem groups (p<0.001). Functional outcomes (p = 0.646), complications (p = 0.318), and readmission rates (p = 0.402) were similar across groups. However, hospital stay was significantly shorter in the rectangular stem groups (p = 0.015).

Conclusion

The introduction of a new rectangular femoral stem did not result in a significant learning curve affecting subsidence, complications, or functional outcomes. The stem demonstrated improved lateral canal filling and was associated with reduced hospital stay, suggesting a safe transition to this design without compromising early outcomes.

1. Introduction

Total hip arthroplasty (THA) is one of the most common and most successful procedures in medicine.¹ Even though the majority of outcomes for THA's are positive, there are ongoing innovations in various aspects of the surgery. One ongoing area of study is improvement to the THA components, including both the femoral stem and acetabular shell.².

Although a new component may have theoretical technological advances over an older model, a surgeon may be reluctant to introduce new components into their practice. This can result from many factors, including comfort with the current implant, satisfaction with outcomes with the current implant, and the potential for a learning curve associated with the introduction of new components. Femoral stem innovations include, but are not limited to, changes to the stem shape to provide improved metaphyseal fitting, changes to the contour and the addition of collars to potentially decrease fracture risk, and changes to the materials used to support greater bony ingrowth.2, 3, 4

Despite the existing literature^3,5, 6, 7, 8, 9 evaluating the learning curve associated with the introduction of new femoral stems in total hip arthroplasty, there are significant limitations in the current literature that highlight the need for our study. Notably, previous research has focused solely on patients receiving new femoral stems without directly comparing outcomes to those of previously established stems. This lack of a control group makes it difficult to determine whether observed complications are truly related to the learning curve of a new implant or are influenced by other factors such as poor surgical technique, approach, experience of the surgeon, or addition of trainees in the operating room. Additionally, some studies did demonstrate an increased risk of adverse events with the introduction of a new femoral stem^3,4,8 while others did not see a clear learning curve and deemed the adoption of a new femoral stem, safe.5, 6, 7

We have therefore conducted a retrospective comparative study assessing the learning curve with the introduction of a new femoral stem. We determined if the introduction of the new femoral stem will affect radiographic outcomes, length of stay, complications and functional outcomes compared to the established femoral stem.

2. Methods

2.1. Participants

This retrospective comparative study was performed from January 2022 until January 2024. Patients undergoing primary THA for osteoarthritis and avascular necrosis were included. Exclusion criteria involved patients with previous acetabular or femoral surgery, post-traumatic arthritis, post-infectious arthritis or childhood conditions such as Perthe's disease, hip dysplasia or slipped capital femoral epiphysis (see Fig. 5).

Fig. 5.

Diaphyseal Canal Filling on Lateral Radiographs

Measurement of diaphyseal canal filling on lateral radiographs. Measurement was taken 100.0 mm distal to the tip of the greater trochanter. The stem diameter at this level was measured and was compared to the inner cortical diameter at the same level.

Patients were separated into 3 groups by both chronologic time and femoral stem used. Group 1, underwent a THA using a metaphyseal loading stem (ML-Taper, Zimmer Biomet, Warsaw, In, USA)⁹ (See Fig. 6). This stem was used by the senior author for the preceding 10 years, and the patients included in Group 1 were the final patients receiving this stem prior to the introduction of the rectangular stem. The second and third group both used a rectangular stem (Collared Aviner Complete stem, Zimmer Biomet, Warsaw, In, USA),¹⁰ and were subdivided further into the “learning curve” group (First half of THA patients performed with the rectangular stem) and the “experienced” group (Second half of THA patients performed with the rectangular stem).

Fig. 6.

Flowchart of included patients.

2.2. Operative technique

All patients received appropriate pre-operative counselling. They were given an appropriate anesthetic, including either a general or spinal anesthetic, based on the anesthesiologists’ recommendations. All surgeries were performed by the same fellowship-trained high-volume arthroplasty surgeon, accompanied by a trained surgical assistant and surgical learners.

Patients were positioned in a lateral decubitus position and supported with a stable positioner. A posterior approach was used for all surgeries, and a minimally invasive approach was used when possible. A cementless titanium hemispherical acetabular cup augmented with one or two screws was used in all patients (Trilogy IT or G7 acetabular shell, Zimmer-Biomet, Warsaw, IN, USA).^11,12 Acetabular liners were either neutral or elevated as deemed necessary by the operative surgeon. The femoral stems were implanted according to the manufacturer's recommended surgical technique aiming for global anteversion of 35–50°.^9,10

All patients were enrolled in a standardized post-operative protocol. If able, patients were discharged early from hospital on post-operative day 1 with a multi-modal analgesic regimen. Patients were instructed to adhere with postoperative hip precautions for 3 months following surgery, involving no flexion past 90°, no adduction past neutral and no internal rotation of the hip.

2.3. Femoral components (see Fig. 1, Fig. 2)

Fig. 1.

Metaphyseal-Loaded Stem (Approval obtained from Zimmer Biomet, Warsaw, Indiana, USA).

Fig. 2.

Rectangular Stems (Approval obtained from Zimmer Biomet, Warsaw, Indiana, USA).

2.3.1. Metaphyseal loaded stem: ML taper stem (Zimmer Biomet, IN, Warsaw, USA)

This is a wedge shaped cementless stem which gains primary stability in the proximal femur due to press-fit implantation. The wedge-shaped contour leads to axial and rotational stability. It is made of titanium alloy (Ti-6AI-4V) and has a proximal metaphyseal porous coating to allow bony ingrowth.⁹

2.3.2. Rectangular stems: Aviner complete stem (Zimmer Biomet, IN, Warsaw, USA)

The stem has a rectangular cross-section with smooth edges to provide rotational stability. The distal tip of the stem features a lateral radius and an anterior-posterior taper to avoid distal potting and to accommodate various femoral morphologies. It is made of a forged titanium alloy which is plasma sprayed of pure titanium coated with a thin layer of hydroxyapatite to enhance bony ingrowth.¹⁰

2.4. Primary outcomes

The primary radiographic outcomes were the amount of subsidence of the femoral component and the percentage of diaphyseal canal filling. Subsidence was compared on the 6-week post-operative supine AP pelvis radiograph to the supine post-operative radiograph performed on the day of surgery. The measurement was taken from the tip of the greater trochanter to the shoulder of the femoral stem (Fig. 3). The distance from the inter-teardrop line to the lesser trochanter was used as a secondary measurement to determine leg lengths. Diaphyseal canal filling was measured on both AP and lateral radiographs of the operative hip, also on 6-week post-operative radiographs. On the AP radiograph, the canal filling was measured 100.0 mm distal to the shoulder of the femoral stem. The diameter between inner cortices of the femoral canal as well as the diameter of the femoral stem at this location were measured, and the percentage of filling was calculated. On the lateral radiograph, the percentage was calculated in the same technique 100.0 mm distal to the tip of the greater trochanter. The trochanter was selected as a landmark as the two femoral stems have different shoulder profiles on the lateral view (see Fig. 4).

Fig. 3.

Subsidence Measurement

Measurement of subsidence on AP radiographs. Measurement was compared between immediate post-operative images and images at six-week follow up. Stem position was measured from the tip of the greater trochanter to the shoulder of the stem in a trajectory parallel to the lateral cortex.

Fig. 4.

Diaphyseal Canal Filling on AP Radiographs

Measurement of diaphyseal canal filling on AP radiographs. Measurement was taken 100.0 mm distal to the shoulder of the stem. The stem diameter at this level was measured and was compared to the inner cortical diameter at the same level.

2.5. Secondary outcomes

Patient-reported outcome measurements included the Oxford Hip Score (OHS) and the EQ-5D-5L Score.^13,14 The OHS is specifically designed to assess pain and function in patients who have undergone hip replacement surgery. It consists of 12 questions, each with five possible responses. It is scored out of 48 with a higher score indicating better hip function and less pain. The minimal clinically important difference (MCID) for the OHS ranges between 5 and 9 points.¹³ The EQ-5D-5L includes factors such as pain and discomfort, mobility, self-care, ability to complete usual activities, and anxiety and depression, as well as an overall health score. Subgroups are scored from 1 to 5 and the health score is scored from 0 to 100. Lower scores in the subgroups indicate better quality of life, while higher scores in the overall health score indicates greater health. The MCID for the EQ-5D-5L score ranges between 8 and 12.¹⁴

We also determined the length of stay for each group, and orthopedic complication rates in each group.

2.6. Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics Version 29.¹⁵

Scale variables were assessed using a one-way analysis of variance (ANOVA) to assess for statistical significance in comparing all three groups. An associated post-hoc Tukey's Test was performed to assess for differences between each combination of individual groups. These scale variables were presented as mean and standard deviation.

Nominal variables were assessed using a Chi-Square test and Pearson's Correlation Coefficient. All variables were compared between all groups in one analysis as well as between each combination of groups in individual analyses.

For all tests, statistical significance was defined as p < 0.05.

3. Results

3.1. Patient characteristics

A total of 115 patients were included in the final analysis. 33 patients were in the control group, 41 in the learning curve group, and 41 in the experienced group. Patient characteristics and surgical factors are shown in Table 1. There were no statistically significant differences between groups in any patient or surgical characteristics.

Table 1.

Patient characteristics.

Demographic		Control Group (n = 33)	Learning Group (n = 41)	Experienced Group (n = 41)	P-value
Age [mean ± SD]		70.1±8.8	65.2±11.3	68.7±10.6	0.113
Sex [n (%)]	Male	19 (57.6)	15 (36.6)	18 (43.9)	0.192
	Female	14 (42.4)	26 (63.4)	23 (56.1)
BMIa [mean ± SD]		28.5±4.6	31.1±5.7	29.4±6.2	0.192
Operative Side [n (%)]	Left	14 (42.4)	22 (53.7)	14 (34.1)	0.202
	Right	19 (57.6)	19 (46.3)	27 (65.9)
Anesthetic Type [n (%)]	General	2 (6.1)	3 (7.3)	4 (9.8)	0.832
	Spinal	31 (93.9)	38 (92.7)	37 (9.0)
Liner [n (%)]	Neutral	14 (42.4)	19 (46.3)	17 (41.5)	0.608
	Elevated	18 (54.5)	22 (53.7)	24 (58.5)
	Other	1 (3.0)	0 (0.0)	0 (0.0)

^aBMI: Body Mass Index.

3.2. Primary outcomes

Primary radiographic outcomes are listed in Table 2.

Table 2.

Radiographic outcomes.

Outcome	Control Group (n = 33)	Learning Group (n = 41)	Experienced Group (n = 41)	P-values (Between All Groups; Control vs Learning; Control vs Experienced; Learning vs Experienced)
Subsidence [mean (mm) ± SD (mm)]	3.7±2.4	3.0±1.6	3.3±2.2	0.381; 0.349; 0.668; 0.839
Canal Filling AP Radiographs [mean (%) ± SD (%)]	86.4±12.0	86.9±8.6	85.6±7.5	0.839; 0.974; 0.939; 0.826
Canal Filling Lateral Radiographs [mean (%) ± SD (%)]	55.0±9.0	66.3±9.0	69.3±10.9	<0.001; < 0.001; < 0.001; 0.346

Femoral stem subsidence was measured as a change in stem position between original post-operative radiographs and radiographs taken 6 weeks after surgery. The control group had a mean subsidence of 3.71 mm, while the learning curve and experienced groups had mean subsidence's of 3.04 mm and 3.30 mm, respectively. These differences were not statistically significant between any group (P-values (between all groups; control vs learning; control vs experiences; learning vs experienced): 0.381 0.349; 0.668; 0.839).

Diaphyseal canal filling on the AP radiographs was measured on 6-week postoperative x-rays as a percentage. The control group had a mean of 86.3 % of the canal filled by the stem, while the learning curve group filled a mean of 86.9 % and the experienced group filled a mean of 85.6 %. These differences were not statistically significant (P-values (between all groups; control vs learning; control vs experiences; learning vs experienced): 0.839; 0.974; 0.939; 0.826).

Diaphyseal canal filling on the lateral radiographs was measured in the same fashion. The control group had a mean canal filling of 55.0 %, the learning curve group had a mean of 66.4 %, and the experienced group of 69.3 %. These differences were statistically significant between the control group and the learning curve group, as well as between the control group and the experienced group. The difference between the learning curve and experienced groups were not significant (P-values (between all groups; control vs learning; control vs experiences; learning vs experienced): <0.001; < 0.001; < 0.001; 0.346).

3.3. Secondary outcomes

3.3.1. Patient-reported outcomes

Patient-reported outcomes were collected through the Oxford Hip Score and the EQ-5D-5L score. Outcomes are listed in Table 3.

Table 3.

Patient-reported outcomes.

Outcome		Control Group (n = 19)	Learning Group (n = 15)	Experienced Group (n = 22)	P-values (Between All Groups; Control vs Learning; Control vs Experienced; Learning vs Experienced)
Oxford Hip Score [mean ± SD]a		43.4±5.0	42.9±9.1	41.4±6.7	0.646; 0.979; 0.642; 0.806
EQ-5D-5L Score [mean ± SD]b	Mobility	1.6±0.8	1.5±0.8	1.6±0.9	0.944; 0.953; 1.000; 0.953
	Self Care	1.3±0.7	1.1±0.3	1.3±0.7	0.512; 0.572; 1.000; 0.572
	Ability to Complete Usual Activities	1.6±0.8	1.4±0.7	1.7±1.0	0.677; 0.787; 0.981; 0.676
	Pain/Discomfort	1.8±1.0	1.3±0.5	1.7±0.9	0.181; 0.167; 0.833; 0.419
	Anxiety/Depression	1.4±0.9	1.3±0.6	1.5±0.9	0.665; 0.861; 0.921; 0.640
	Overall	83.3±14.4	84.9±10.5	77.6±18.5	0.299; 0.956; 0.539; 0.301

^aOxford Hip Score recorded from 0 to 48, with higher scores indicating greater satisfaction.

^bEQ-5D-5L: EuroQol Score consists of 5 subsections graded from 1 to 5, with lower scores indicating greater satisfaction, and an overall score graded from 0 to 100, with higher scores indicating greater satisfaction.

In the Oxford Hip Score there were no statistically significant differences between any groups in the overall score (P-values (between all groups; control vs learning; control vs experienced; experienced vs learning): 0.646; 0.979; 0.642; 0.806).

There were likewise no statistically significant differences in EQ-5D-5L scores in any of the five domains, nor in the overall health score (P-values for overall score: 0.299; 0.956; 0.539; 0.301).

3.3.2. Complications

Complications, length of stay, and readmission rate are listed in Table 4.

Table 4.

Complications, length of stay, readmission rate.

Outcome Complications [n (%)]		Control Group (n = 33)	Learning Group (n = 41)	Experienced Group (n = 41)	P-values (Between All Groups; Control vs Learning; Control vs Experienced; Learning vs Experienced)
		3a	2b	0	0.318; 0.445; 0.143; 0.359
Length of Stay [n (%)]	<24 h	0 (0.0)	0 (0.0)	3 (7.3)	0.015; 0.021; 0.054; 0.186
	24–48 h	24 (72.7)	38 (92.7)	34 (82.9)
	>48 h	9 (27.3)	3 (7.3)	4 (9.8)
Readmissions [n (%)]		0 (0.0)	1 (2.4)	0 (0.0)	0.402; 0.366; 1.000; 0.314

^aComplications in the control group included two intraoperative calcar fractures and one anterior hip dislocation.

^bComplications in the learning group included one intraoperative calcar fracture and one prosthetic joint infection.

Three patients in the control group experienced complications. This included two periprosthetic fractures (calcar fractures), both of which were identified at the time of surgery and treated with cerclage wiring and full weight bearing postoperatively without any further intervention. One patient had an anterior hip dislocation, which was found in the recovery unit and required immediate revision surgery without any further intervention.

Two patients in the learning curve group experienced complications. This included one periprosthetic fracture (calcar fracture), which was again identified intraoperatively and immediately repaired with cerclage wiring and no change in weight-bearing status, and one prosthetic joint infection, requiring a two-stage revision.

There were no complications in the experienced group. The difference in complication rate was not statistically significant (P-values (between all groups; control vs learning; control vs experienced; learning vs experienced): 0.318; 0.445; 0.143; 0.359).

3.3.3. Length of stay

Length of stay was recorded for all patients. Length was characterized into three groups: those remaining in hospital for less than 24 h, for between 24 and 48 h, and for greater than 48 h.

The majority of patients were discharged between 24 and 48 h post-operatively. Only 3 patients were discharged within 24 h of surgery, all of which were in the experienced group. Of the 16 patients discharged greater than 48 h post-operatively, nine were in the control group, three in the learning group, and four in the experienced group. These differences were statistically significant overall, as well as in focused analysis between the control and learning group, but not between the control and experienced group or between the learning and experienced group (P-values: 0.015; 0.021; 0.054; 0.186).

3.3.4. Readmission rates

Readmission events were recorded for every patient. Only one from the learning group was readmitted, and no patients in the other groups. This difference was not statistically significant overall or between any groups (P-values: 0.402; 0.366; 1.000; 0.314).

4. Discussion

In this study, there was a statistically significant difference in lateral femoral canal filling in favour of the rectangular stem design compared to the metaphyseal loading stem. Length of stay was significantly shorter in the rectangular stem design group compared to the metaphyseal loading group. There were no statistical differences between the groups in regards to subsidence, complications, readmission, PROMS and AP canal filling.

4.1. Canal filling

There was statistically significant difference in antero-posterior canal filling (AP – canal filling) (P-values (between all groups; control vs learning; control vs experiences; learning vs experienced): <0.001; < 0.001; < 0.001; 0.346). This can be mainly explained by design differences. The Metaphyseal loading stem design is a tapered design from the medial to the lateral side. It emphasizes a proximal fitting design to help improve better load-sharing in the metaphyseal area. It also has a smaller antero-posterior taper to help with stability. The AP-taper is in the range of 3–5° compared to the ML taper which ranges between 5 and 7°.^9,10 In contrast, the rectangular stems have a quadrangular cross-section with smooth edges to improve rotational stability. Due to the increased dimension in the Antero-Posterior plane of the rectangular stem, we can deduct that the AP- filling will be larger but the medial-lateral plane will be comparable to the metaphyseal loading stems.^9,10 Comparing the median AP diameter of the metaphyseal loading stem to the rectangular stem it measures 11.8 mm and 13.08 mm respectively. The medial lateral diameter measures 28.6 mm and 29.6 respectively.^9,10

4.2. Learning curve

Multiple studies have evaluated the learning curve following the introduction of new femoral stems in total hip arthroplasty.3, 4, 5, 6, 7, 8 The number of included patients in these studies has ranged between 92 and 451. All the studies are retrospective and follow up ranges from 90 days to 61 months.

The results are quite conflicting regarding the learning curve, with some studies demonstrating a clear risk with introducing new femoral stems,^3,4,8 while others do not demonstrate an increased risk.5, 6, 7 Interestingly, two studies associated the direct anterior approach with an increased risk of adverse events with the introduction of a new femoral stem.^3,7

4.3. Subsidence

Minimizing subsidence postoperatively is crucial in the success of total hip arthroplasty. It is demonstrated that subsidence more than 2–3 mm leads to poorer outcomes.^16,17 Multiple studies have demonstrated a low subsidence rate with metaphyseal loading stems.^18,19 Both cited studies were retrospective with follow-up periods ranging between 1 and 6.1 years. They concluded that vigorous broaching, avoidance of under sizing of the femoral component, maximizing mediolateral stem dimensions and confirmation of broach stability with the torsional test optimizes stability of the final component.¹⁸

Increased surgeon experience has been associated with an improved survivorship of the femoral stem.²⁰ One retrospective cohort study demonstrated that for every five revision surgical procedures performed by a surgeon, the risk for revision decreases by a factor of 0.93 (95 % confidence interval, 0.58–0.90).²¹ In the current study, all the procedures were performed by the senior author who is a high-volume adult reconstruction surgeon at a tertiary center. This may explain why no statistically significant differences were detected in the patient reported outcome measures, postoperative complications or 90-day readmissions.

4.4. Collared stems

The rectangular stem utilized in the learning and experienced groups was collared. Theoretical advantages of collared stems include axial stability and rotational stability.²² Collared stems have shown decreased revision rates compared to collarless stems at 20 years (5.7 % vs 7.5 %, respectively).²³ This holds true for direct anterior approach, anterolateral approach and posterolateral approach. Multiple studies have demonstrated less migration with collared stems compared to collarless stems.^16,17 In contrast, one randomized controlled trial of 204 THAs, followed for 45 months, demonstrated no difference in subsidence, osteolysis, radiolucencies or proximal femoral remodeling between collarless and collared femoral stems.²⁴

4.5. Length of stay

The length of stay was significantly shorter in the learning group (rectangular stem) compared to the control group (established stem). One potential confounding reason for this decrease in length of stay is the introduction of rapid discharge criteria at our institution at the same time as the introduction of the new rectangular femoral stem. Factors instituted to decrease the length of stay included a great emphasis on perioperative hydration, aggressive treatment of nausea and vomiting, adequate counselling of patients preoperatively to prepare them for rapid discharge, multimodal pain management postoperatively, and early mobilization.^25,26

4.6. Clinical implications

Because the rectangular studies do demonstrate better AP filling, surgeons can speculate that there might be better initial rotation stability, with potentially better long-term osteointegration. One caveat with better canal filling is alteration of load distribution with the potential for increased proximal stress shielding. Seeing that the patient-reported outcome measures, complications, and readmission rates were statistically similar, it is reassuring that surgeons can adopt a new stem without compromise to patient care.

4.7. Future research

Future research should focus on long term outcome studies assessing implant survivorship, functional outcomes, radiographic outcomes (stress shielding or bone remodeling), and late complications.

4.8. Strengths and limitations

This study does have strengths and limitations. It has a large sample size with multiple outcome measures. However, it is a retrospective study that lacks generalizability. It was performed by a single adult reconstruction surgeon in a tertiary academic center.

The study does have a relatively short follow up period, which limits assessment of long-term implant survival, bone remodeling, late functional differences, and late complications. As the authors mainly looked at two types of stems, it is difficult to make conclusions of other femoral stems.

It is also possible that the learning curve may be shorter than the 41 patients included in this study and therefore the study was unable to detect a difference in the learning curve group. However, decreasing the size of the learning curve group would decrease the power of the study, and preventing this would only be possible through analysis of multiple surgeons’ learning curve groups to increase the sample size. Reproducing the statistical analysis with only the first 10 patients in the learning curve group produces a mean subsidence of 4.3 mm ± 1.7 mm. This is not statistically significant compared to the control group, which is reassuring though not statistically sound.

5. Conclusion

This study demonstrates that the adaptation of a new stem can be safely achieved with similar complication, subsidence, and readmission rates. In addition, patient functional outcomes in the short term were similar. Surgeons should, however, understand the geometry of the new stem being adopted, especially if study of long-term outcomes in the literature is lacking. Because all surgeries were performed by a single adult reconstruction surgeon at a single tertiary academic center, the results should be interpreted with caution and cannot be generalized.

CRediT authorship contribution statement

Kyle Goldstein: Methodology, Formal analysis, Investigation, Resources, Writing – original draft, Writing – review & editing, Supervision, Project administration. Michaela Nickol: Writing – review & editing, Supervision, Project administration. Johannes M. van der Merwe: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Resources, Data curation, Writing – original draft, Writing – review & editing, Visualization, Supervision, Project administration.

Informed consent

N/A.

Patient and guardian consent

This is not applicable to this study – No identifiable names, images, videos are in the manuscript.

Ethical approval and consent to participate

Approved on the August 1, 2023; Bio-Reb 3704, Consent obtained from all patients to participate in the study.

Availability of supporting data

All the raw data and materials described in the manuscript is available upon requests to any scientist wishing to use them for non-commercial purposes.

Consent for publication

Not applicable.

Disclosures

The authors have no conflicts of interest to declare.

Ethics statement

Approved on the August 1, 2023; Bio-Reb 3704.

Data available statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.