Demographic, clinical, symptom, and psychological characteristics of patients (N = 203) prior to surgery.

<p>Demographic, clinical, symptom, and psychological characteristics of patients (N = 203) prior to surgery.</p

Preoperative Pain, Symptoms, and Psychological Factors related to Higher Acute Pain Trajectories during Hospitalization for Total Knee Arthroplasty - Fig 4

<p>Trajectories of worst pain by gender (A), average preoperative pain intensity prior to surgery (B), and worst preoperative pain intensity (C) from before surgery until postoperative day 4. Higher/lower differences in Fig 4 B to C were calculated based on 1 standard deviation above/below the mean. The coefficients are adjusted for all other variables in the model.</p

Potential predictors of intercept (I), piecewice 1 (PW1), piecewice 2 (PW2), linear (L), quadratic (Q) and cubic (C) components for average and worst pain.

<p>Potential predictors of intercept (I), piecewice 1 (PW1), piecewice 2 (PW2), linear (L), quadratic (Q) and cubic (C) components for average and worst pain.</p

Hierarchical linear models of the trajectories for average and worst postoperative pain.

<p>Hierarchical linear models of the trajectories for average and worst postoperative pain.</p

Differences between the lymphedema and no lymphedema groups.

<p>A – Differences between the lymphedema and no lymphedema groups in the percentages of patients who were homozygous for the common allele (AA) or heterozygous or homozygous for the rare allele (AG+GG) for rs315721 in lymphocyte cytosolic protein 2 (LCP2). B – Differences between the lymphedema and no lymphedema groups in the percentages of patients who were homozygous or heterozygous for the common allele (TT+TG) or homozygous for the rare allele (GG) for rs849530 in neuropilin-2 (NRP2). C – Differences between the lymphedema and no lymphedema groups in the percentages of patients who were homozygous or heterozygous for the common allele (AA+AT) or homozygous for the rare allele (TT) for rs158689 in protein tyrosine kinase (SYK). D – Differences between the lymphedema and no lymphedema groups in the percentages of patients who were homozygous for the common allele (CC) or heterozygous or homozygous for the rare allele (CT+TT) for rs3176861 in vascular cell adhesion molecule 1 (VCAM1).</p

Multiple logistic regression analyses for FOXC2. LCP2, NRP2, SYK, VCAM1, and VEGF-C genotypes and halotypes to predict the development of lymphedema.

<p>For each model, the first three principal components identified from the analysis of ancestry informative markers as well as self-report race/ethnicity (i.e., White, Black, Asian/Pacific Islander, Hispanic/Mixed ethnic background/Other) were retained in all models to adjust for potential confounding due to race or ethnicity (data not shown). Predictors evaluated in each model included genotype (FOXC2 haplotype A03 composed of the rs34221221 “C” allele and the rs1035550 “C” allele; LCP2 rs315721: AA versus AG+GG; NRP2 rs849530: TT+TG versus GG; NPR2 haplotype F01 composed of the rs849530 “G” allele, the rs950219 “G” allele, and the rs3771052 “G” allele; SYK rs158689: AA+AT versus TT; VCAM1 rs3176861: CC versus CT + TT; VEGFC haplotype B03 composed of the rs3775202 “G” allele and the rs3775195 “C” allele), BMI (kilograms/meter squared), stage of disease, SLNB, number of lymph nodes removed, receipt of chemotherapy prior to or following surgery, and receipt of radiation therapy following surgery.</p><p>Abbreviations: BMI  =  body mass index; CI  = confidence interval; FOXC2  =  Forkhead box protein C2; LCP2  =  Lymphocyte cytosolic protein 2; NRP  =  neuropilin-2; SLNB  =  sentinel lymph node biopsy; SYK  =  spleen tyrosine kinase; VCAM1  =  vascular cell adhesion molecule 1; VEGFC  =  vascular endothelial growth factor-C.</p

NRP2 Gene Structure and Linkage Disequilibrium.

<p>An ideogram of neuropilin 2 (NRP2) is presented above the white bar that represents the physical distance along human chromosome 2 (chr2: 206,255,469–206,371,102; genome assembly 36.3, NM_201266.1). Exons are represented as thick bars. Gray lines connecting the exons represent introns. Reference sequence identifiers (rsID) for each single nucleotide polymorphism (SNP) are plotted both in terms of their physical distance (i.e., the white bar at the top of the figure) and equidistantly to render the pairwise linkage disequilibrium (LD) estimates that were calculated and visualized with Haploview 4.2. The gene structure for NRP2 was rendered with FancyGene 1.4. The correlation statistics (r² and D') are provided in the heatmap. LD-based haplotype block definition was based on the D' confidence interval method. The haploblock is indicated in a bolded triangle and its component SNPs are rendered in bold font. Pairwise D' values (range: 0–1, inclusive) were rendered in color, with darker red diamonds representing D' values approaching 1.0. When the r² values (range of 0–100, inclusive) are not equal to 0 or 100, they are provided in a given diamond. The 3-SNP haplotype associated with LE consists of one rare and two common alleles of three SNPs (rs849530 “G” rare allele, rs950219 “G” common allele, rs3771052 “G” common allele) located in intron 1 of the gene.</p

VEGFC Gene Structure and Linkage Disequilibrium.

<p>An ideogram of vascular endothelial growth factor C (VEGFC) is presented above the white bar that represents the physical distance along human chromosome 4 (chr4: 177,841,685–177,950,889; genome assembly 36.3, NM_005429.2). Exons are represented as thick bars. Gray lines connecting the exons represent introns. Reference sequence identifiers (rsID) for each single nucleotide polymorphism (SNP) are plotted both in terms of their physical distance (i.e., the white bar at the top of the figure) and equidistantly to render the pairwise linkage disequilibrium (LD) estimates that were calculated and visualized with Haploview 4.2. The gene structure for VEGFC was rendered with FancyGene 1.4. The correlation statistics (r² and D') are provided in the heatmap. LD-based haplotype block definition was based on the D' confidence interval method. The haploblock is indicated in a bolded triangle and its component SNPs are rendered in bold font. Pairwise D' values (range: 0–1, inclusive) were rendered in color, with darker red diamonds representing D' values approaching 1.0. When the r² values (range of 0–100, inclusive) are not equal to 0 or 100, they are provided in a given diamond. The 2-SNP haplotype associated with LE consists of one rare and one common allele of two SNPs (rs3775202 “G” rare allele, rs3775195 “C” common allele) located in intron 4 of the gene. Of note, the strong linkage disequilibrium estimates observed in public databases (i.e., HapMap) resulted in the selection of 8 SNPs that tagged the entire coding region of the VEGFC gene.</p

FOXC2 Gene Structure and Linkage Disequilibrium.

<p>An ideogram of forkhead box C2 (FOXC2) is presented above the white bar that represents the physical distance along human chromosome 16 (chr16: 85,158,358–85,160,040; genome assembly 36.3, NM_005251.2). Exons are represented as thick bars. Reference sequence identifiers (rsID) for each single nucleotide polymorphism (SNP) are plotted both in terms of their physical distance (i.e., the white bar at the top of the figure) and equidistantly to render the pairwise linkage disequilibrium (LD) estimates that were calculated and visualized with Haploview 4.2. The gene structure for FOXC2 was rendered with FancyGene 1.4. The correlation statistic (r² and D') is provided in the heatmap. LD-based haplotype block definition was based on the D' confidence interval method. The haploblock is indicated in a bolded triangle and its component SNPs are rendered in bold font. Pairwise D' value (range: 0–1, inclusive) was rendered in color, with darker red diamond representing D' value approaching 1.0. When the r² value (range of 0–100, inclusive) is not equal to 0 or 100, it is provided in a given diamond. The 2-SNP haplotype associated with LE is composed of one rare and one common allele of two SNPs located in the immediate early promoter (rs34221221; rare “C” allele) and immediately downstream of the FOXC2 coding region (rs1035550; common “C” allele).</p

Differences in demographic and clinical characteristics between patients with (n = 155) and without (n = 387) lymphedema.

<p>Abbreviations: kg  =  kilograms, m² – meter squared, NS  =  not significant, SD  =  standard deviation.</p