Abstract
Background
The foot posture is age dependent. The purpose of this study was to investigate the relationship between the 6-item version of the foot posture index (FPI) and other clinical, foot anthropometric, radiological measurements for the foot position in 5–8-year-old children.
Methods
A total of 301 participants with a mean age of 6.4 ± 1.14 years were enrolled in the study. Children were examined physically, clinically, and radiologically to measure the FPI and navicular drop (ND) test, resting calcaneal stance position (RCSP) angle, Chippaux–Smirak index (CSI), Staheli index (SI), calcaneal pitch (CP) angle, talocalcaneal angle (TCA), and the first lateral metatarsal angle. Tibial torsions, internal rotation of the hip as an indirect method of femoral anteversion, and Beighton scale were analyzed for factors associated with flatfoot prevalence.
Results
The study included children with normal and flexible flatfeet. Statistical analysis showed a significant FPI score correlation with other parameters (SI, CSI, RCSP, ND, CP, TMA, and TCA showed strong and moderate correlations, p < 0.001). Overall, the strongest associates are CSI (β = 0.34) and ND (β = 0.28). Other indicators have relatively small relationships with the FPI.
Conclusion
A positive correlation was observed between FPI-6 and ND test, CSI in 5–8-year-old children. All three prominent foot posture indicators (FPI-6, ND, and CSI) might be used as a primary or preferred tool in clinical practice.
1 Introduction
Flatfoot is a common foot posture in children and a frequent concern for parents by the appearance of children’s feet [1,2]. The foot posture is age dependent and the exact time when the medial longitudinal arch of the foot is formed is still not exactly known [2]. According to studies, a flat arch is typical for children at birth but resolves spontaneously until 6 years of age [1,3]. In contrast to other studies, the arch of the child’s feet is fully formed in about 10 years of age [2,4].
In most clinical practices, a non-dynamic assessment of children’s feet is performed to classify foot posture excluding pathological feet [1,5]. This includes four main methods of assessment: (a) non-quantitative visual assessment, (b) anthropometric measurements (resting calcaneal stance position [RCSP] angle, navicular drop [ND] test, and medial longitudinal arch angle), (c) various footprint-based analysis (Chippaux–Smirak index [CSI], Staheli arch index [SI], etc.), and (d) radiological examinations with various measurements. This includes MRI, ultrasound, and laser scanners [5,6,7,8]. Radiographic procedure is the golden standard for evaluating the medial longitudinal arch height [9,10], even though radiographic measures typically provide only a uni-plantar assessment of the foot posture [5]. In contrast, the foot posture index (FPI-6) is a clinical and multiplanar tool that displays three planes for the assessment of the foot. FPI-6 classifies the posture of the foot in pronated, supinated, or neutral positions [5,10]. Previous studies showed that FPI-6 is a reliable test for measuring the foot position; therefore, it has acquired popularity over the years [1,4,5,11,12].
Another biomechanical parameter is widely used to diagnose resting foot posture – RCSP [1,5,13]. The RCSP has a high degree of reliability, independent of age, height, and weight [13]. According to studies, validity and reliability of RCSP angle are relatively less common than those of FPI-6 [5], especially at different ages of the child.
ND represents the medial ‘drift’ of the navicular bone from neutral to resting stance position. It reflects movements of the medial longitudinal arch and is associated with the pronated foot [6]. In a cohort of adults, the FPI-6 showed an excellent correlation with the ND [10]. However, a recent study has concluded an ND as an unreliable measure with only fair agreement across test sessions [5].
Various footprint-based analyses for foot arch assessment have been developed and are used widely. The CSI and SI are regarded as reliable by many investigators in calculating arch development and are recommended in screening for flatfoot in preschool-aged children [7,14,15]. The FPI-6 showed a good correlation with the CSI and SI in adults [10].
The configuration of the arch is determined by age, height, weight, foot progression angle, sex, joint hypermobility, tibial torsion, femoral anteversion, hindfoot alignment, and occurrence of physiological knock knee [16].
Because of this, in our study, inclusion criteria were set for 5–8 years children after the rapid progression of the plantar arch. In addition, the relationship between FPI-6 and RCSP, ND, SI, CSI, X-ray measurements – calcaneal pitch (CP) angle, talocalcaneal angle (TCA), lateral first metatarsal angle (TMA), tibial torsions, and internal/external rotation of hip is currently unclear. Therefore, the purpose of this study was to investigate the relationship between FPI-6 and other clinical (tibial torsion, femoral anteversion), footprint (CSI, SI), foot anthropometric (ND, RCSP), radiological (TCA, CP, and TMA) measurements for foot position in 5–8-year-old children.
Results of this study could provide information on whether ND, RCSP, SI, CSI, X-ray measurements, and clinical measurements could be used as a clinical, radiological measuring tool for pediatric flatfoot. This is the first study to reveal a correlation between FPI-6 scores for foot posture and footprint parameters (CSI, SI), clinical parameters (tibial, femoral torsions, RCSP, and ND), and radiological parameters (TMA, CP, and TCA) in 5–8 years flexible flatfeet and non-flatfeet children.
2 Methods
2.1 Patients
The sample of interest was 5–8-year-old children. Between April 2019 and February 2020, a total of 301 participants (146 boys and 145 girls) with a mean age of 6.4 ± 1.14 years were enrolled in the cross-sectional comparative study. The study participants visited the hospital for general orthopedic and foot examination without pain as a regular checkup that is mandatory in the country. The eligibility was defined as follows:
Inclusion criteria: asymptomatic flexible flatfeet (positive Jack’s test, FPI ≥ 6); non-flatfeet, with no evident joint deformities (FPI 0–5); aged 5–8 years;
Exclusion criteria: foot pain, injury to the lower limbs during the previous 12 months, congenital abnormalities, cerebral palsy, motor dysfunction, prior foot surgery, the use of foot orthoses, a fixed foot deformity.
We obtained information about age, sex, body weight, height, and underlying diseases. The sample was well balanced regarding gender and age, with a slight overrepresentation of a 5-year-old group. Table 1 shows the demographic and anthropometric profile of the participants.
Characteristics of participants
Characteristic | Value | n | % |
---|---|---|---|
Gender | Boys | 146 | 50.2 |
Girls | 145 | 49.8 | |
Age | 5 years | 81 | 27.8 |
6 years | 70 | 24.1 | |
7 years | 70 | 24.1 | |
8 years | 70 | 24.1 | |
Mean ± SD | 6.4 ± 1.14 | ||
Weight (kg) | Mean ± SD | 25.0 ± 4.98 | |
Height (cm) | Mean ± SD | 121.8 ± 8.07 | |
BMI | Mean ± SD | 16.69 ± 1.953 |
Abbreviation: SD, standard deviation.
This study is based on a screening protocol to determine the foot posture of both feet using the FPI-6 [17]. Participants were allocated to one of the two-foot posture groups based on the screening protocol and qualified for the non-flatfeet normal group if static foot measurements were within one standard deviation of the mean of normative data for the FPI-6. Participants were assigned to the flexible flatfeet group if static foot measurements were greater than one standard deviation of the mean of normative data for the FPI-6.
The following functional tests were performed to assess the ability to correct deformities: (1) the great toe extension test (Jack’s test) and (2) the tip-toe standing test [13].
The study was conducted under the Declaration of Helsinki and approved by the local research ethics committee on April 08, 2019, under registration number BE-2-2. All parents and/or legal guardians of the participating children signed a written informed consent statement before these participants were brought into the study.
2.2 Clinical examination
The clinical examination was documented on a standard document sheet developed for routine use in orthopedic examination and was conducted in the same way for all patients. Parameter groups specifically for flexible flatfoot (FFF) diagnosis were evaluated in this study [3]: (1) passive ankle dorsiflexion and plantar flexion was measured with ruler-based goniometry. The patient was positioned supine, the knee extended (dorsiflexion knee 0°), and the ankle was redressed to the neutral position and the foot was prevented from supinating during dorsiflexion. The dorsiflexion was repeated with the knee flexed (dorsiflexion knee 90°). The dorsiflexion was performed looking for a tight Achilles tendon, thus differentiating between the equinovalgus and the planovalgus subtypes of FFF [18]. Less than 10° of dorsiflexion with the knee 0°, 90° suggests that the entire Achilles tendon is tightened. Less than 10° of dorsiflexion just with the knee 0° implies isolated gastrocnemius tightness [4]. (2) Torsional deformities: for tibial torsion deformity, the thigh-foot angle was calculated for both legs with the patient prone and the knees flexed to 90° and the ankle positioned in neutral [19]. A goniometer was placed along the long axis of the thigh and a line bisecting the calcaneus and ray of the second metatarsal. The angle between the second ray and the thigh axis was regarded as the thigh-foot angle. The negative value refers to the internal rotation of the tibia, whereas the positive value refers to the external rotation [20]. For the femoral torsion deformity, internal and external hip rotation was measured with the patient prone and the knees flexed to 90°. The hip midpoint of rotation was measured. Normal internal rotation of the hips limited to 50°. Raised internal rotation of the hip is considered to have an angle above 60° [3,21] and it is an indirect measurement for femoral anteversion in children. Moreover, it has the relationship between the flatfoot and femoral anteversion [21].
2.2.1 Beighton
In this study, the Beighton hypermobility score was used to measure joint mobility. This scale consists of five items, with a total score ranging from 0 to 9 [22,23]. This scale is relatively insensitive and inappropriate for different ages, sex, and ethnic groups. A total score of >4 is used to define generalized hypermobility of joints in this study [22,24].
2.2.2 Anthropometric measures
Height and weight were measured using a calibrated altimeter and digital scales with subjects wearing minimal clothing. The BMI was then calculated (weight (kg)/height (m2)).
2.2.3 Foot posture assessments
The ND was used to measure the medial longitudinal arch according to Brody [5,10]. To evaluate the ND, the navicular height was measured by maintaining the subtalar joint in the neutral position under non-weight-bearing and weight-bearing conditions. ND test >9 mm represented a pronated foot type, 5–9 mm a neutral foot, and <5 mm a supinated foot [5]. This test has been reported to demonstrate moderate intra-tester reliability (intra-class correlation coefficient 0.61–0.79) and fair inter-rater reliability (0.57) [5,22,25].
The FPI-6 was used to evaluate the weight-bearing foot posture in the standing position [11]. Each criterion of the FPI-6 is scored on a 5-point scale (ranging from −2 to +2), and the scores are summed to provide a total score (ranging from −12 to +12) for the determination of foot posture [1] [22,26]. The FPI-6 is commonly used in research and clinical practice. It can be highly pronated (+10 to +12), pronated (+6 to +9), normal (0 to +5), supinated (−1 to −4), and highly supinated (−5 to −12). The index has been reported to demonstrate good reliability in adults and children [27]. Inter-observer reliability for the FPI-6 in the pediatric population is reflected in the consistent weighted Kappa value obtained (K w = 0.86) by Morrison and Ferrari in a sample of children aged 5–16 years [27,28]. For every child in this study, the FPI-6 measurements were obtained for both feet by one experienced podiatrist.
RCSP was assessed based on the method described by Root [29]. Briefly, participants were asked to lie face-down on a bed parallel to the ground with their feet over the edge of the bed. An investigator examined their feet manually and put three dots on the upper, middle, and lower parts of the calcaneus to draw a bisection line regardless of fat around the calcaneus. RCSP was measured when individuals were standing with their feet fist-width apart. The angle between the bisector of the calcaneus and the perpendicular line to the ground was measured. Flatfoot was defined when either of the feet had greater than 4° valgus of RCSP angle [1,30].
2.2.4 Footprint-based examination
Each patient was asked to put both feet on two Harris and Beath footprint mats while sitting on a chair [31]. The child then stood up to a standing position with even weight on both feet and returned to the sitting position to complete the footprint recording. Footprint data were rejected when apparent overshoot or imbalance had occurred on standing up or significant foot movement had occurred during recording. The footprint data from both feet were used [32]. Then the CSI and SI were used to measure the flatness of the footprint. The foot arch index measurements had previously shown excellent inter-rater reliability (SI 0.95; CSI 0.98) and test–retest reliability (SI 0.96; CSI 0.97) [32].
The CSI is the ratio between the smallest length of mid-foot and the largest length of the metatarsal head regions. Five categories are described for the medial longitudinal arch classification according to CSI: 0%: foot with elevated arch; 0.1–29.9%: foot with a morphological normal arch; 30–39.9%: intermediate foot; 40–44.9%: foot with a lowered arch; and 45% or higher flatfoot [14].
The SI is the ratio between the smallest length of the mid-foot and the largest length of the heel. Values between 0.44 and 0.89 were considered as normal values [14].
2.2.5 Radiological measurements
Two bilateral radiographs consisting of lateral and anteroposterior views were obtained with the children in the bipedal standing position under weight-bearing conditions. On lateral weight‐bearing radiography, three angles were obtained: the talo-first metatarsal angle (TMA), talo‐calcaneal angle (TCA), and CP angle [33]. Flatfoot was defined as one of the following abnormal radiological findings: TCA > 45°, TMA > 4°, or CP < 20° [17,34]. The lateral X-ray measurements have a wide variation inter-rater reliability (TCA 0.568; TMA 0.46; CP 0.95) and intra-rater reliability (TCA 0.66; TMA 0.68; CP 0.96) in the assessment of pediatric flatfoot deformity [35].
The main descriptive characteristics of analyzed indicators under study are shown in Table 2.
Descriptive characteristics of analyzed indicators
Indicators | Mean | SD | Normality | Percentiles | |||
---|---|---|---|---|---|---|---|
Skewness | Kurtosis | 25th | 50th | 75th | |||
Foot posture index (FPI-6) | 5.49 | 3.948 | −0.06 | −1.68 | 2.0 | 7.0 | 9.0 |
Staheli arch index (SI) | 1.05 | 0.37 | 0.13 | −1.11 | 0.7 | 1.2 | 1.3 |
Chippaux–Smirak index (CSI) | 60.27 | 21.31 | −0.05 | −1.70 | 38.2 | 69.5 | 79.2 |
Navicular drop (ND) test | 10.91 | 5.410 | −0.08 | −1.66 | 5.0 | 12.0 | 16.0 |
Resting calcaneal stance position (RCSP) | 5.62 | 2.969 | −0.16 | −0.89 | 3.0 | 6.0 | 8.0 |
Beighton score (hypermobility) | 4.06 | 1.669 | 0.65 | 0.22 | 3.0 | 4.0 | 5.0 |
Tibial torsion (thigh-foot angle) | 4.24 | 8.317 | 0.17 | 0.35 | −2.0 | 5.0 | 9.0 |
Foot dorsiflexion (knee 90°) | 26.27 | 3.384 | 0.14 | −0.07 | 25.0 | 25.0 | 30.0 |
Foot dorsiflexion (knee 0°) | 17.35 | 2.778 | −0.17 | −0.13 | 15.0 | 17.5 | 20.0 |
Foot plantar flexion | 38.86 | 3.967 | −0.17 | −0.10 | 36.0 | 40.0 | 40.0 |
Internal hip rotation | 54.53 | 11.521 | 0.42 | 0.26 | 45.0 | 55.0 | 60.0 |
External hip rotation | 47.40 | 9.099 | 1.02 | 0.57 | 42.0 | 45.0 | 52.0 |
Calcaneal pitch (CP) | 16.46 | 6.211 | 0.11 | −1.20 | 10.0 | 17.0 | 22.0 |
Lateral talo-first metatarsal angle (TMA) | 12.51 | 9.582 | 0.65 | −0.93 | 4.0 | 9.0 | 21.0 |
Talocalcaneal angle (TCA) | 44.20 | 10.900 | −0.11 | −1.15 | 34.0 | 45.5 | 53.0 |
Abbreviation: SD, standard deviation.
The mean of the FPI-6 was 5.5 pts, and the mean of the Beighton score was 4.1 pts.
2.3 Data analysis
Statistical analysis was performed with “IBM SPSS Statistics for Windows” (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.). The descriptive analysis included means ± standard deviations (SD), the percentiles for continuous data as well as check for normality using skewness and kurtosis indicators. The categorical variables were described in absolute numbers (n) and percentages.
The comparison of means was conducted using Student’s t-test for independent samples concerning Levene’s test for equality of variances. The strength of associations between particular indicators and FPI was assessed using three ways: (1) correlation coefficient, (2) effect size, and (3) linear regression. The bivariate associations with FPI were assessed using Pearson’s correlation coefficient. The effect sizes were calculated using Cohen’s d coefficient. The multivariate analysis included linear regression modeling. The three scenarios to define the strongest associates of FPI were chosen to see how consistent the findings are and if the strongest associates are robust independently from analytical scenarios.
The level of statistical significance was set at p < 0.05.
3 Results
The study included 301 children with normal and flexible flatfeet. By comparing these two groups, majority of indicators differed significantly – footprint-based parameters (SI, CSI, p < 0.001), foot anthropometric parameters (ND, RCSP, p < 0.001), radiological foot parameters (CP, TMA, TCA, p < 0.001), and hypermobility parameter (Beighton score, p < 0.001). The majority of associated indicators showed highly significant differences between study groups (Table 3).
Comparison of study indicators in children with flat and non-flatfeet
Indicators | Non flatfeet | Flatfeet | Difference | |||
---|---|---|---|---|---|---|
Mean | SD | Mean | SD | t | p | |
Staheli arch index (SI) | 0.68 | 0.12 | 1.35 | 0.20 | −49.35 | <0.001 |
Chippaux–Smirak index (CSI) | 37.71 | 3.84 | 78.75 | 7.38 | −86.22 | <0.001 |
Navicular drop (ND) | 5.23 | 1.31 | 15.56 | 1.93 | −76.71 | <0.001 |
Beighton score (hypermobility) | 3.69 | 1.70 | 4.37 | 1.58 | −5.00 | <0.001 |
Tibial torsion (thigh-foot angle) | 4.69 | 7.97 | 3.87 | 8.59 | 1.19 | 0.234 |
Foot dorsiflexion (knee 90°) | 26.40 | 3.50 | 26.17 | 3.29 | 0.81 | 0.417 |
Foot dorsiflexion (knee 0°) | 17.51 | 2.83 | 17.22 | 2.73 | 1.26 | 0.207 |
Foot plantar flexion | 38.50 | 4.11 | 39.16 | 3.82 | −1.99 | 0.047 |
Internal hip rotation | 53.00 | 11.10 | 55.79 | 11.72 | −2.92 | 0.004 |
External hip rotation | 46.80 | 8.83 | 47.89 | 9.30 | −1.44 | 0.151 |
Resting calcaneal stance position (RCSP) | 2.90 | 1.72 | 7.84 | 1.63 | −35.54 | <0.001 |
Calcaneal pitch (CP) | 22.34 | 3.00 | 11.65 | 3.37 | 39.95 | <0.001 |
Lateral talo-first metatarsal angle (TMA) | 4.64 | 2.73 | 18.95 | 8.28 | −29.04 | <0.001 |
Talocalcaneal angle (TCA) | 34.54 | 6.73 | 52.11 | 6.31 | −32.43 | <0.001 |
Abbreviation: SD, standard deviation; t, Student’s t-test.
Statistical analysis showed a significant FPI score correlation with other parameters (SI, CSI, RCSP, ND, CP, TMA, and TCA showed strong and moderate correlations, p < 0.001) based on Pearson’s coefficient (r). Because of similarity, effect sizes (d) among indicators were counted and the largest were CSI (d = 6.98), SI (d = 4.02), ND (d = 6.27), and CP (d = 3.35). Overall, the correlation and effect size calculations revealed very consistent patterns (Table 4).
Study indicators and FPI: correlations and effect sizes
Indicators | r | p | d |
---|---|---|---|
Staheli arch index (SI) | 0.862 | <0.001 | 4.02 |
Chippaux–Smirak index (CSI) | 0.919 | <0.001 | 6.98 |
Navicular drop (ND) | 0.913 | <0.001 | 6.27 |
Beighton score (hypermobility) | 0.173 | <0.001 | 0.42 |
Tibial torsion (thigh-foot angle) | −0.052 | 0.211 | 0.10 |
Foot dorsiflexion (knee 90°) | −0.033 | 0.429 | 0.07 |
Foot dorsiflexion (knee 0°) | −0.053 | 0.203 | 0.10 |
Foot plantar flexion | 0.092 | 0.027 | 0.17 |
Internal hip rotation | 0.123 | 0.003 | 0.24 |
External hip rotation | 0.090 | 0.029 | 0.12 |
Resting calcaneal stance position (RCSP) | 0.781 | <0.001 | 2.95 |
Calcaneal pitch (CP) | 0.826 | <0.001 | 3.35 |
Lateral talo-first metatarsal angle (TMA) | 0.720 | <0.001 | 2.32 |
Talocalcaneal angle (TCA) | 0.774 | <0.001 | 2.69 |
Abbreviation: r: Pearson’s correlation coefficient, d: Cohen coefficient for the effect sizes.
To eliminate possible interaction effects between the analyzed indicators, we conducted a multivariate analysis. The linear regression revealed the same pattern – that the strongest associates are footprint-based parameters CSI (β = 0.34) and ND (β = 0.28). Other strong correlations are SI and CP, with all other indicators having relatively small relationships with the FPI (Table 5).
Comparison of study indicators as potential predictors of FPI: linear regression analysis
Indicator | B | β | p | VIF |
---|---|---|---|---|
Staheli arch index (SI) | 1.65 | 0.16 | <0.001 | 4.82 |
Chippaux–Smirak index (CSI) | 0.06 | 0.34 | <0.001 | 8.22 |
ND (ND) | 0.20 | 0.28 | <0.001 | 8.53 |
Beighton score (hypermobility) | −0.04 | −0.02 | 0.253 | 1.09 |
Tibial torsion (thigh-foot angle) | −0.01 | −0.02 | 0.114 | 1.07 |
Foot dorsiflexion (knee 90°) | 0.01 | 0.01 | 0.754 | 2.36 |
Foot dorsiflexion (knee 0°) | −0.03 | −0.02 | 0.393 | 2.39 |
Foot plantar flexion | 0.01 | 0.01 | 0.603 | 1.19 |
Internal hip rotation | 0.00 | 0.00 | 0.887 | 1.12 |
External hip rotation | 0.01 | 0.02 | 0.108 | 1.10 |
Resting calcaneal stance position (RCSP) | 0.06 | 0.04 | 0.067 | 3.16 |
Calcaneal pitch (CP) | 0.07 | 0.12 | <0.001 | 3.58 |
Lateral talo-first metatarsal angle (TMA) | 0.01 | 0.03 | 0.112 | 2.36 |
Talocalcaneal angle (TCA) | 0.02 | 0.05 | 0.035 | 2.92 |
Abbreviation: VIF, the variance inflation factor.
4 Discussion
The FFF topic, especially asymptomatic form, is under very tense discussion widely by doctors, representatives of various fields of science, scientists, and parents of anxious children. However, this debate is still stuck at the lowest level of the evidentiary pyramid in evidence-based medicine and to treat or not to treat FFF is in the experienced physician’s hands – opinion [2]. The strength of the present study is that the topic of the study is of importance to practitioners given the high number of (clinical, anthropometrical, and radiological) presentations to pediatric orthopedic services that are related to lower limb conditions. The foot only constitutes 14% of all the musculoskeletal consultations and parental concerns regarding foot development are high on that list [36]. Parents who are often worried about the child’s feet posture bring the child to an orthopedic. These children are usually with “abnormal” rotational deformities of the lower extreme [6,21,37]. Zafiropoulos et al. [21] showed that children, aged between 3 and 6 years with a raised internal rotation of the hip (≥60°) and as an indirect measurement of femoral anteversion, have a relationship between flatfoot and femoral anteversion (F = 168.1, p < 0.001, r = 0.53). They concluded that it is necessary to investigate further with ages above 6 years. In our study, the FPI-6 tool was used to include the patients instead of footprint measurement contact index II. The internal rotation of the hip was 55.79° ± 11.72 in the flatfoot group and 53.00° ± 11.10 in the non-flatfoot group. This is statistically nonsignificant and we did not notice any statistically significant correlations with the FPI.
Some studies [38,1] assessed the correlation between FPI-6 and RCSP angle in elementary school students (8–13 years) and adolescents (11–16 years), and declared moderate correlation. In the current study, we also found a moderate correlation to FPI-6 (flatfeet r = 0.781 and r = 0.714, respectively, p < 0.001). However, no correlation was observed between the first three measures after comparing the effect sizes. This raises doubts, because FPI-6 that is proven with validity and reliability is widely used by clinicians. On the contrary, RCSP angle is used by orthotic specialists. Furthermore, Cho, Park, and Nam found no statistically significant association of BMI with FPI-6. Martinez-Nova et al. [39] have also shown the FPI-6 minimal relationship with weight, height, and BMI. Because of this fact, we have not searched the relationships between these factors. Yet, several reports have shown that obesity and overweight children typically display flatter feet relative to their leaner counterparts; however, the cause of their flatter feet is unknown [38,40,41,42].
In the current study, we demonstrated that the ND and footprint indexes – CSI and SI – had the strongest correlations with FPI-6 in flatfoot children and a moderate relationship in non-flatfoot children. This finding is consistent with other recent findings by our group. It agrees with other studies [10,38], where the correlation between the ND and the FPI-6 was excellent (P < 001; r = 0.818), including that between the footprint parameters and the FPI-6 was good as well (P < 0.001; r s = |0.663–0.703|). Contrary to findings in our study and based on the data of the study by Langley, Cramp, and Morrison, [5], it was recently reported that an ND is not an acceptable measure for characterizing the foot. Interestingly, ND was the least consistent measure for classifying the foot (K w = 4). As opposed to our study, the ND test was the second choice indicator as a potential predictor of FPI-6. It might be explained by age, where the adult population was studied (29 ± 6 years). However, the vast majority of studies in literature have been conducted with adults. As children’s feet are changing over time (cessation of time is unknown [2]), comparisons made with adults can mask other related factors. Further research is needed.
On the contrary, most of the studies have highlighted the frequent use of FPI-6 as a sensitive, specific, and predictive tool in the evaluation of pediatric FFF, which is very important not only for researchers but also for clinicians [43,44]. However, in the pediatric population, this excellent diagnostic tool has its limitations in terms of its sensitivity at different ages of the child. Limitations occur when the natural history of the pediatric FFF, as a morphology that usually reduces with age, is not taken into account [2]. The FPI-6 score would be predicted to change with each year of childhood [2,39]. Martínez-Nova et al., in the prospective 3-year study [39], demonstrated a pronated and highly pronated FPI-6 category where the pediatric foot had converted to a neutral FPI-6 foot type as age increased. They declared that pronated foot posture can be expected in children aged less than 9–10 years and there can be a spontaneous reduction without any treatment. Other studies also confirm this [36,45]. What is more, in clinical practice, is that this fact should be a strong signal to the pediatric orthopedist, because it highlights the need for caution when interpreting results based on the FPI-6 diagnostic tool in the pediatric population. A future follow-up of patients as they grow older is necessary. Despite this important observation, the majority of existing studies have generally included the larger age gap of children such as 6–18, 3–15, and 3–17 years old [2,44]. The results do not emphasize at what age gap the pediatric foot posture changes during development. Therefore, much of the existing literature has limited external validity for practitioners working with children with FFF. Our research addresses two of these discussed concerns by including non-flatfeet and asymptomatic flatfeet participants of ages 5–8 where the majority of outcome measures are valid and reliable indicators of FFF or related to FFF.
Even though the high prevalence of flatfoot in children is related to both the anatomy of the foot variability [46] and the lack of diagnostic criteria and diagnostic test latitudes [47], the difference between symptomatic FFF and asymptomatic FFF remains an assessment of pain, fatigue in the child’s feet, and other subjective sensations [48]. Interestingly, differences in foot kinematics between symptomatic and asymptomatic FFF could not be found [3,49]. Bohm et al. [3] concluded the substudy that it is important to differentiate decompensated FFF, because those are more prone and require surgical interventions, even if they are not yet associated with pain. This means we need to go back to surgical planning and radiological evaluation pre- and post-surgery in asymptomatic FFF. However, studies on the correlation of FPI-6 with footprints, clinical evaluation, gait analysis, and radiographs are limited. In our study, lateral radiographic measurements of feet were included (TMA, TCA, and CP angles). Radiography is a highly reliable gold-standard measure for the assessment of the skeletal alignment of the foot in static weight bearing position [44]. All these angles had moderate-to-strong correlations with FPI-6 in our researched population. However, the linear regression analysis showed that CP has the highest potentiality to predict FPI-6. This conflicts the results of previous studies [33,44,50], where the TMA angle was chosen to represent the foot posture based on ease of measurement, good reliability, and the degree to which it reflects the static foot posture. Lee et al. [33] had found that RCSP significantly correlated with the TMA angle, but the CP angle was not significantly correlated with either TMA or TCA. However, they used RCSP in their study instead of FPI-6. Furthermore, they declared that TMA, the most predictable parameter obtained on simple X‐ray, was well correlated with TCA and RCSP. In general, clinical and radiologic measurements did not show significant correlations. This observation in our study found that the CP angle has the greatest potential to predict FPI-6. It allows future studies in the pediatric population to make a more targeted choice of a more valuable measured angle, as well as a more reliable choice for radiologists.
To the best of our knowledge, this paper also appears to be original in terms of participants and outcome measure approaches. The result is potentially valuable, particularly for practitioners, radiologists, rehabilitation professionals, orthotic shoe manufacturers, and those presenting with symptoms of FFF or asymptomatic FFF. Understanding the posture of the foot in developing children helps to detect any persisting deviations beyond a certain stage of development. It also provides a margin for timely intervention to avoid possible deformities and dysfunctions. Although there are several methods available, one of the main limitations with static measurements of foot posture is that generally only one clinical technique is used in each investigation. Because of the differences in sample characteristics and measurement procedures, it is difficult to compare the results of different studies and make an informed decision on the most appropriate technique. As the foot complex is almost developed in adolescence, there is a need for normative baseline data in this population, which can help to compare the deviations seen in children with impaired foot posture. These values can also be used to monitor the outcome of regular examinations for foot impairments. Finally, this research is one of the few in the area that is attempting to answer questions raised in the pediatric orthopedic community, which are listed in the systematic review paper by Uden et al. [2]. In multiple literature, FFF is a very targeted foot type and often “diagnosed” using one or more non-validated assessments [47]. This raised the first question regarding which of these foot measures, if any, should be used to assess the posture of the developing foot. The FPI-6 is a validated and accurate method for quantifying standing foot posture and determining pediatric FFF [27,44,51]. According to our study results from the footprint-based measures, the CSI had the strongest associations with FPI-6 as well as with the ND parameter. In addition, the CP angle had the strongest correlation from radiological foot posture characteristics in comparison to most usable parameters for diagnosing FFF. The second question was about the level of importance of these indicators and, if any, should be placed on the static posture of the developing foot, because of the notable absence of functional and clinical data in the literature. The use of foot anthropometric measurements is found to be a salient role in the analysis of the foot types using the ND, RCSP, and other parameters in the 5–8-year age group. Our study noted, next to FPI-6 which is very important method in daily practice [43], stands firmly and ND, CP, CSI, and SI in the pediatric 5–8 years population. However, this needs to be highlighted for caution when directly interpreting results.
This study had several limitations. First, this was a cross-sectional study. The enrolled sample and results cannot be extrapolated to the entire population. In addition, further longitudinal studies should be conducted to investigate between clinical, radiological, and gait analysis assessments. Second, all measurements were performed by the same practitioner and recorded as one measurement. Intra-rater reliability was not confirmed in FPI and other measurements. The high reliability of FPI-6 is described in the literature [52]. Third, we did not include children with symptomatic FFF. In the literature review, we did not succeed to find any articles evaluating the totality of visual, anthropometric, clinical, radiological, and gait analyses indicators in the study. Nothing was found by comparing the characteristics of normal feet, asymptomatic FFF, and symptomatic FFF, especially studies on larger sample size in larger and varied geographical regions. Finally, all measurements and examinations of the patient were performed in 1 day. By assessing the scope of the data and the age of the children (aged 5–8 years), it could have affected error even if there were breaks between measurements.
5 Conclusions
A positive correlation was observed between FPI-6 and ND test, CSI in 5–8-year-old children. In addition, all three prominent foot posture indicators (FPI-6, ND, and CSI) might be used as primary or preferred tools in clinical practice determining the shape of the foot. This is the first research investigation that shows a correlation between FPI-6 and other clinical, anthropometrical, and radiological parameters together in children at 5–8 years. There is potential for future research in this field with more longitudinal designs and across different samples and races to see if these findings are consistent or specific to certain subgroups.
Abbreviations
- BMI
-
body mass index
- CP
-
calcaneal pitch angle
- CSI
-
Chippaux–Smirak index
- FFF
-
flexible flatfoot
- FPI-6
-
foot posture index six
- ND
-
navicular drop
- RCSP
-
resting calcaneal stance position
- SI
-
Staheli arch index
- TCA
-
talocalcaneal angle
- TMA
-
lateral first metatarsal angle
Appendix
Study parameters of the investigations into paediatric foot posture and foot posture index six (FPI-6), show that FPI-6 and footprint measures have dominated foot posture assessment
Study: author, country | Year of publication | Design | Participans (n) | Age (years) | Method of foot posture assessment | Highlights of the study |
---|---|---|---|---|---|---|
Fatma A Hegazy et al., United Arab Emirates, Egypt | 2020 | A cross-sectional | 612 | 6–18 | FPI-6Foot X-ray: TMA | FPI-6 is valid and with moderate diagnostic accuracy for determining paediatric FFF |
Yongjin Cho et al., Republic of Korea | 2019 | Retrospective comparative | 208 | 8–13 | FPI-6RCSP | Moderate correlation between FPI-6 and RCSP angle |
Alfonso Martínez-Nova et al., Spain | 2018 | Prospective | 1,032 | 5–118–14 | FPI-6 | Assessing FPI-6: children’s foot posture shifts toward neutral as age increases |
Sriraghunath S et al., India | 2018 | A cross-sectional | 391 | 11–16 | FPI-6RCSPND | A large correlation both in adolescent girls and boys between FPI-6 and anthropometric measurements (ND, RCSP) |
Fiona Hawke et al., Australia, New Zeland | 2016 | Cross-sectional | 30 | 7–15 | FPI-6 | Children with a more pronated foot type exhibited greater lower limb and whole-body flexibility, but not greater ankle joint flexibility |
Gill et al., USA | 2016 | Cross-sectional | 254384 | 2–1718–80 | Footprints: CSI, KIND | Arch height indices (CSI, KI) were correlated with navicular height (ND) |
Isabel CN Sacco et al., Brazil, Germany | 2015 | Longitudinal for German populatio,Brazilian – Cross-sectional | 94391 | 3–10 | Footprints: CSI,SI | Revealed anthropometric differences in absolute forefoot and rearfoot widths of German and Brazilian children, but a similar longitudinal arch development |
Angela M Evans, Australia | 2011 | Cross-sectional | 140 | 7–10 | FPI-6 | Did not find a positive relationship between increased body weight and flatter foot posture |
George Zafiropoulos et al., UK and Greece | 2009 | Prospective | 621 | 3–6 | Footprints: CI IIClinical: internal hip rotation | A highly significant correlation between flat foot and raised internal rotation of hip |
Jung H. Lee et al., Korea | 2009 | Observational | 13 | 6.6 ± 2.3 | Clinical: femoral anteversion, femoral internal rotation, femoral external rotation, tibial torsion (thigh -foot angle)RCSPFoot X-ray: TMA, TCA, CP, metatarsal adductionCTGait | TMA was related to the degree of RCSP. Larger TCA contributed to decreased maximal external rotation and increased maximal internal rotation |
-
Funding statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
-
Competing interests: The authors declare that they have no competing interests. The authors declare no conflict of interest. This manuscript has been read and approved by all authors and is not under consideration for publication elsewhere.
-
Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
-
Author contributions: ŽS designed the study and collected data. ŽS and ČE analyzed the data. ŽS, ČE, and BV wrote the manuscript. ŽS and BV reviewed and edited the manuscript. All authors read and approved the final manuscript.
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© 2021 Saidas Žukauskas et al., published by De Gruyter
This work is licensed under the Creative Commons Attribution 4.0 International License.
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- Clinical analysis of 11 cases of nocardiosis
- Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
- Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
- Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
- Relation between IL-8 level and obstructive sleep apnea syndrome
- circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
- Nomogram prediction model for renal anaemia in IgA nephropathy patients
- Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
- NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
- A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
- Clinical and prognostic features of MMP-2 and VEGF in AEG patients
- The value of miR-510 in the prognosis and development of colon cancer
- Functional implications of PABPC1 in the development of ovarian cancer
- Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
- Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
- Prediction of improvement after anterior cruciate ligament reconstruction
- Effluent Osteopontin levels reflect the peritoneal solute transport rate
- circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
- Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
- Association between hair cortisol concentration and metabolic syndrome
- Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
- Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
- Knee alterations in rheumatoid arthritis: Comparison of US and MRI
- Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
- lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
- Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
- Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
- Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
- Travelers’ vaccines and their adverse events in Nara, Japan
- Association between Tfh and PGA in children with Henoch–Schönlein purpura
- Can exchange transfusion be replaced by double-LED phototherapy?
- circ_0005962 functions as an oncogene to aggravate NSCLC progression
- Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
- Serum intact fibroblast growth factor 23 in healthy paediatric population
- Algorithm of rational approach to reconstruction in Fournier’s disease
- A meta-analysis of exosome in the treatment of spinal cord injury
- Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
- Dexmedetomidine may decrease the bupivacaine toxicity to heart
- Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
- Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
- External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
- miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
- HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
- Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
- Cell population data in identifying active tuberculosis and community-acquired pneumonia
- Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
- Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
- 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
- Association of gene polymorphisms with women urinary incontinence
- Influence of COVID-19 pandemic on stress levels of urologic patients
- miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
- miR-519d downregulates LEP expression to inhibit preeclampsia development
- Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
- Fluorescent light energy modulates healing in skin grafted mouse model
- Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
- Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
- Severe postoperative hyperbilirubinemia in congenital heart disease
- Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
- Clinical factors predicting ureteral stent failure in patients with external ureteral compression
- Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
- Triple-Endobutton and clavicular hook: A propensity score matching analysis
- Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
- Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
- miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
- Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
- The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
- Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
- No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
- circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
- Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
- Educational program for orthopedic surgeons’ influences for osteoporosis
- Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
- GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
- lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
- Anticoagulation is the answer in treating noncritical COVID-19 patients
- Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
- Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
- VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
- Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
- Treatment of osteoporosis with teriparatide: The Slovenian experience
- New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
- Superenhancer–transcription factor regulatory network in malignant tumors
- β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
- Clinical features of atypical tuberculosis mimicking bacterial pneumonia
- Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
- Effect of electromagnetic field on abortion: A systematic review and meta-analysis
- miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
- MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
- Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
- miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
- Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
- MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
- Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
- circATP2A2 promotes osteosarcoma progression by upregulating MYH9
- Prognostic role of oxytocin receptor in colon adenocarcinoma
- Review Articles
- The function of non-coding RNAs in idiopathic pulmonary fibrosis
- Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
- Role of cesarean section in the development of neonatal gut microbiota: A systematic review
- Small cell lung cancer transformation during antitumor therapies: A systematic review
- Research progress of gut microbiota and frailty syndrome
- Recommendations for outpatient activity in COVID-19 pandemic
- Rapid Communication
- Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
- Use of microspheres in embolization for unruptured renal angiomyolipomas
- COVID-19 cases with delayed absorption of lung lesion
- A triple combination of treatments on moderate COVID-19
- Social networks and eating disorders during the Covid-19 pandemic
- Letter
- COVID-19, WHO guidelines, pedagogy, and respite
- Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
- COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
- What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
- Case Report
- Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
- CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
- Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
- Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
- Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
- Pulmonary parenchymal involvement caused by Tropheryma whipplei
- Mediastinal mixed germ cell tumor: A case report and literature review
- Ovarian female adnexal tumor of probable Wolffian origin – Case report
- Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
- Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
- Primary orbital ganglioneuroblastoma: A case report
- Primary aortic intimal sarcoma masquerading as intramural hematoma
- Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
- Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
- Chondroblastoma of mandibular condyle: Case report and literature review
- Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
- Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
- Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
- High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
- Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
- Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
- Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
- Retraction
- Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
- An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
- Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
Articles in the same Issue
- Research Articles
- Identification of ZG16B as a prognostic biomarker in breast cancer
- Behçet’s disease with latent Mycobacterium tuberculosis infection
- Erratum
- Erratum to “Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome”
- Research Articles
- GPR37 promotes the malignancy of lung adenocarcinoma via TGF-β/Smad pathway
- Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
- Additional baricitinib loading dose improves clinical outcome in COVID-19
- The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
- SLC12A8 plays a key role in bladder cancer progression and EMT
- LncRNA ATXN8OS enhances tamoxifen resistance in breast cancer
- Case Report
- Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy
- Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background
- Research Articles
- TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137
- CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis
- LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs
- Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates
- Rapid Communication
- COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution
- Case Report
- Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature
- An infertile female delivered a baby after removal of primary renal carcinoid tumor
- Research Articles
- Hypertension, BMI, and cardiovascular and cerebrovascular diseases
- Case Report
- Coexistence of bilateral macular edema and pale optic disc in the patient with Cohen syndrome
- Research Articles
- Correlation between kinematic sagittal parameters of the cervical lordosis or head posture and disc degeneration in patients with posterior neck pain
- Review Articles
- Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
- Research Articles
- Thermography in the diagnosis of carpal tunnel syndrome
- Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
- Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
- The influence of smoking in minimally invasive spinal fusion surgery
- Impact of body mass index on left atrial dimension in HOCM patients
- Expression and clinical significance of CMTM1 in hepatocellular carcinoma
- miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
- Comparison of multiple flatfoot indicators in 5–8-year-old children
- Early MRI imaging and follow-up study in cerebral amyloid angiopathy
- Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
- miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
- Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
- Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
- Review Articles
- The ambiguous role of mannose-binding lectin (MBL) in human immunity
- Case Report
- Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
- Fertility problems in males carrying an inversion of chromosome 10
- Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
- Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
- Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
- Skull hemophilia pseudotumor: A case report
- Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
- Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
- Clinicopathologic features of Good’s syndrome: Two cases and literature review
- Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
- Research Articles
- Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
- Significance of nucleic acid positive anal swab in COVID-19 patients
- circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
- Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
- Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
- Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
- Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
- Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
- FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
- Platelet-rich fibrin: Basics of biological actions and protocol modifications
- Accurate diagnosis of prostate cancer using logistic regression
- miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
- Prognostic significance of TRIM28 expression in patients with breast carcinoma
- Integrative bioinformatics analysis of KPNA2 in six major human cancers
- Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
- A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
- Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
- Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
- Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
- COVID-19 severity in relation to sociodemographics and vitamin D use
- Clinical analysis of 11 cases of nocardiosis
- Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
- Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
- Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
- Relation between IL-8 level and obstructive sleep apnea syndrome
- circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
- Nomogram prediction model for renal anaemia in IgA nephropathy patients
- Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
- NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
- A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
- Clinical and prognostic features of MMP-2 and VEGF in AEG patients
- The value of miR-510 in the prognosis and development of colon cancer
- Functional implications of PABPC1 in the development of ovarian cancer
- Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
- Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
- Prediction of improvement after anterior cruciate ligament reconstruction
- Effluent Osteopontin levels reflect the peritoneal solute transport rate
- circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
- Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
- Association between hair cortisol concentration and metabolic syndrome
- Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
- Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
- Knee alterations in rheumatoid arthritis: Comparison of US and MRI
- Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
- lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
- Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
- Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
- Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
- Travelers’ vaccines and their adverse events in Nara, Japan
- Association between Tfh and PGA in children with Henoch–Schönlein purpura
- Can exchange transfusion be replaced by double-LED phototherapy?
- circ_0005962 functions as an oncogene to aggravate NSCLC progression
- Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
- Serum intact fibroblast growth factor 23 in healthy paediatric population
- Algorithm of rational approach to reconstruction in Fournier’s disease
- A meta-analysis of exosome in the treatment of spinal cord injury
- Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
- Dexmedetomidine may decrease the bupivacaine toxicity to heart
- Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
- Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
- External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
- miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
- HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
- Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
- Cell population data in identifying active tuberculosis and community-acquired pneumonia
- Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
- Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
- 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
- Association of gene polymorphisms with women urinary incontinence
- Influence of COVID-19 pandemic on stress levels of urologic patients
- miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
- miR-519d downregulates LEP expression to inhibit preeclampsia development
- Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
- Fluorescent light energy modulates healing in skin grafted mouse model
- Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
- Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
- Severe postoperative hyperbilirubinemia in congenital heart disease
- Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
- Clinical factors predicting ureteral stent failure in patients with external ureteral compression
- Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
- Triple-Endobutton and clavicular hook: A propensity score matching analysis
- Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
- Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
- miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
- Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
- The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
- Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
- No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
- circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
- Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
- Educational program for orthopedic surgeons’ influences for osteoporosis
- Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
- GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
- lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
- Anticoagulation is the answer in treating noncritical COVID-19 patients
- Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
- Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
- VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
- Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
- Treatment of osteoporosis with teriparatide: The Slovenian experience
- New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
- Superenhancer–transcription factor regulatory network in malignant tumors
- β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
- Clinical features of atypical tuberculosis mimicking bacterial pneumonia
- Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
- Effect of electromagnetic field on abortion: A systematic review and meta-analysis
- miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
- MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
- Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
- miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
- Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
- MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
- Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
- circATP2A2 promotes osteosarcoma progression by upregulating MYH9
- Prognostic role of oxytocin receptor in colon adenocarcinoma
- Review Articles
- The function of non-coding RNAs in idiopathic pulmonary fibrosis
- Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
- Role of cesarean section in the development of neonatal gut microbiota: A systematic review
- Small cell lung cancer transformation during antitumor therapies: A systematic review
- Research progress of gut microbiota and frailty syndrome
- Recommendations for outpatient activity in COVID-19 pandemic
- Rapid Communication
- Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
- Use of microspheres in embolization for unruptured renal angiomyolipomas
- COVID-19 cases with delayed absorption of lung lesion
- A triple combination of treatments on moderate COVID-19
- Social networks and eating disorders during the Covid-19 pandemic
- Letter
- COVID-19, WHO guidelines, pedagogy, and respite
- Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
- COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
- What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
- Case Report
- Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
- CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
- Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
- Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
- Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
- Pulmonary parenchymal involvement caused by Tropheryma whipplei
- Mediastinal mixed germ cell tumor: A case report and literature review
- Ovarian female adnexal tumor of probable Wolffian origin – Case report
- Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
- Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
- Primary orbital ganglioneuroblastoma: A case report
- Primary aortic intimal sarcoma masquerading as intramural hematoma
- Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
- Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
- Chondroblastoma of mandibular condyle: Case report and literature review
- Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
- Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
- Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
- High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
- Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
- Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
- Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
- Retraction
- Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
- An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
- Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning