Cross-cultural adaptation and validation of a Spanish version of the self-administered foot evaluation questionnaire (SAFE-Q).

BACKGROUND: The self-administered foot evaluation questionnaire is a comprehensive measure for assessing the perception of patients regarding their foot-related problems. However, it is currently only available in English and Japanesse. Therefore, this study aimed to cross-culturally adapt the questionnaire to Spanish and assess its psychometric properties. METHODS: The methodology recommended by the International Society for Pharmaco Economics and Outcomes Research for translating and validating patient-reported outcome measures was followed for the Spanish translation. After a pilot study with 10 patients and 10 controls, an observational study was carried out between March and December 2021. The Spanish version of the questionnaire was filled by 100 patients with unilateral foot disorders, and the time spent to complete each questionnaire was recorded. Cronbach's alpha was calculated to analyze the internal consistency of the scale and Pearson's correlation coefficients for the degree of inter-subscale associations. RESULTS: The maximum correlation coefficient for the Physical Functioning, Daily Living, and Social Functioning subscales was 0.768. The inter-subscale correlation coefficients were significant (p < 0.001). Additionally, the value of Cronbach's alpha for the whole scale was 0.894 (95% confidence interval, 0.858-0.924). The values of Cronbach's alpha varied between 0.863 and 0.889 when the value of one of the five subscales was suppressed, which can be considered a measure of good internal consistency. CONCLUSION: The Spanish version of the questionnaire is valid and reliable. The method followed for its transcultural adaptation ensured its conceptual equivalence with the original questionnaire. Health practitioners can use the self-administered foot evaluation questionnaire as a complementary method to assess the interventions performed for ankle and foot disorders among native Spanish speakers; however, further research is necessary to assess its consistency for use by populations from other Spanish-speaking countries.

Temporal Changes in Clinical Outcomes after Minimally Invasive Surgery for Hallux Valgus Correction in Women without Postoperative Complications.

Minimally invasive surgery (MIS) is currently used to correct hallux valgus deformities. Most studies reporting on MIS techniques to correct hallux valgus deformities included patients with postoperative complications. These reported complications, with an average rate of 23%, had significant negative effects on the clinical outcomes in this patient population. In the present study, a cohort of 63 women who underwent MIS hallux valgus correction was assessed preoperatively and at a mean follow-up of 1.0, 4.7, and 6.5 years using the American Orthopaedic Foot and Ankle Society (AOFAS) scale and the Manchester Oxford Foot Questionnaire (MOXFQ). The main criterion for inclusion in this cohort was a lack of complications during the entire follow-up period. The results showed significant improvements in both AOFAS and MOXFQ scores between the preoperative and 1-year follow-up assessments. By contrast, clinically small and nonsignificant changes were observed among postoperative follow-up values. The number of enrolled patients needs to be increased in future studies, with different surgeons and techniques included. Nevertheless, our study findings will inform patients about the outcomes they can expect over the years if no complications occur.

Isometric Knee Muscle Strength and Patient-Reported Measures Five Years after Anterior Cruciate Ligament Reconstruction: Comparison of Single versus Dual Autograft Hamstring Tendon Harvesting.

There is some controversy regarding the use of one or two hamstring tendons for anterior cruciate ligament reconstruction (ACLR). In this study, two cohorts of 22 male patients underwent an ACLR with hamstring tendon autografts. One cohort was reconstructed through an all-inside technique with the semitendinosus tendon (ST group) and the other with the semitendinosus and gracilis tendons (ST-G group). Anterior tibial translation (ATT), Lysholm, and IKDC scores were assessed preoperatively and five years postoperation. Additionally, isometric knee muscle strength was manually measured in both groups and in another cohort of 22 uninjured control male subjects five years after the operation. There were no significant differences in ATT and Lysholm scores between the operated groups. The IKDC score was lower in the ST-G group than in the ST group­9.57 (CI 14.89−4.25) (p < 0.001). No significant differences between injured and uninjured knees were detected in hamstring to quadriceps ratio strength and quadriceps limb symmetry index of the two operated groups, but the hamstring limb symmetry index was significantly lower in the ST-G group than in the ST and control groups. This study shows that using an ST-G autograft for ACLR yielded less flexor strength and worse results in some patient-reported outcome measures (PROM) than using an ST autograft five years after the operation. The observed results let us suggest that the use of one autograft hamstring tendon for ACLR is clinically preferable to the use of two hamstring tendons.

Pre- and Post-Operative Relationship between Radiological Measures and Clinical Outcomes in Women with Hallux Valgus.

The surgical correction of a hallux valgus (HV) deformity improves radiological parameters and clinical outcomes. However, it is not known how these improvements are related between themselves. In this retrospective study, 73 women were assessed preoperatively and 60 months after HV surgical correction. Several radiological parameters were measured: the hallux valgus angle (HVA), I−II intermetatarsal angle (IMA) and sesamoid position. The functional outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) Hallux Metatarsophalangeal-Interphalangeal (HMI) scale, and patient-reported outcomes (PROMs) were recorded with the Manchester−Oxford Foot Questionnaire (MOXFQ). A pre−post-surgery comparison of radiological and clinical values was performed, the correlation among them was studied and the differences pre−post-surgery in the radiological measurements compared with those for the clinical outcomes were studied. The results show that all the radiological parameters, functional outcomes and PROMs improved significantly from their pre-operative values to the follow-up values. Multivariate regression analysis showed a significant relationship (p < 0.001) between the differential pre−post-surgery AOFAS scoring only with two sesamoid position differential pre−post-surgery measures: position of medial sesamoid (PMS) and translation of the first metatarsal head (TMH). However, no significant association was observed between the pre−post-surgery radiological differences and the pre−post-surgery MOXFQ scoring.

Impedance Planimetry and the Changing Paradigm of Esophageal Dysphagia.

OBJECTIVES: Patients presenting with dysphagia can encounter a pathway to therapy and relief that is expensive and frustrating. High resolution impedance planimetry (HRIP) is a new mechanism for enhancing and possibly hastening that process. A balloon with integrated pressure sensors is utilized to measure luminal geometry and pressure by volume-controlled distention. Esophagogastric junction (EGJ) distensibility and body contractility are assessed at the time of other endoscopic procedures. Here we describe a single-center experience utilizing HRIP in the endoscopic evaluation of patients presenting with dysphagia. METHODS: A prospectively maintained registry of patients undergoing impedance planimetry assessments at an academic medical center was queried for demographics, procedural details, and patient-reported outcomes. RESULTS: Data was reviewed for 122 procedures performed by two providers. HRIP was performed in 63 (52%) patients for initial dysphagia assessment, 36 (30%) for follow-up assessment, and 20 (16%) as a procedural adjunct at the time of other planned procedures. HRIP contractile response was characterized as normal in 36%, absent in 32%, and diminished/disorganized in 14%. These results motivated clinical planning for surgical referral in 7 (5%) patients, 31 (26%) additional testing, and 82 (68%) continued medical management and follow-up. DISCUSSION: HRIP is an emerging endoscopic modality which can streamline diagnostic work-up and therapeutic planning for patients with symptomatic dysphagia. Using functional esophageal assessment at the time of other diagnostic and therapeutic procedures, HRIP may expedite care and lead to improved patient satisfaction and clinical outcomes.

Correlation among Knee Muscle Strength and Self-Reported Outcomes Score, Anterior Tibial Displacement, and Time Post-Injury in Non-Coper Anterior Cruciate Ligament Deficient Patients: A Cross-Sectional Study.

Little attention has been paid to knee muscle strength after ACL rupture and its effect on prognostic outcomes and treatment decisions. We studied hamstrings (H) and quadriceps (Q) strength correlation with a patient-reported outcome measures score (International Knee Documentation Committee, IKDC), anterior tibial translation (ATT), and time post-injury in 194 anterior cruciate ligament deficient patients (ACLD) who required surgery after a failed rehabilitation program (non-copers). The correlation between knee muscle strength and ATT was also studied in 53 non-injured controls. ACLD patients showed decreased knee muscle strength of both the injured and non-injured limbs. The median (interquartile range) values of the H/Q ratio were 0.61 (0.52-0.81) for patients' injured side and 0.65 (0.57-0.8) for the non-injured side (p = 0.010). The median H/Q ratio for the controls was 0.52 (0.45-0.66) on both knees (p < 0.001, compared with the non-injured side of patients). The H/Q, ATT, and time post-injury were not significantly correlated with the IKDC score. ATT was significantly correlated with the H/Q of the injured and non-injured knees of patients, but not in the knees of the controls. Quadriceps strength and H/Q ratio were significantly correlated with ATT for both limbs of the patients. IKDC score correlated significantly with the quadriceps and hamstrings strengths of the injured limb but not with the H/Q ratio, ATT or time passed after injury.

Anterior tibial translation and patient-reported outcomes after anterior cruciate ligament reconstruction with a tape locking screw: A 5-year follow-up study.

BACKGROUND: The Tape Locking Screw system (TLS) is a recognised technique used in anterior cruciate ligament reconstruction (ACLR). However, only a few previous studies have reported associated outcomes, all of which had been examined over a short-term period. The aim of this study was to assess the time-dependent changes in the objective and patient-reported outcome measures (PROM) in a group of patients with anterior cruciate ligament deficiency who have been operated on with this technique. HYPOTHESIS: Previously reported satisfactory short-term outcomes following TLS persist for several years after the operation. PATIENTS AND METHODS: This study was a retrospective observational study including 26 patients, who were followed after unilateral ACLR with TLS. Anterior tibial translation (ATT) was measured in both knees using the KT-1000 arthrometer and two PROMs: International Knee Documentation Committee (IKDC) and Lysholm subjective form scores were examined preoperatively, 6 months postoperatively, and annually for 5 years thereafter in all patients. RESULTS: One patient suffered a rupture of the graft, and one patient had a screw loosening. Two patients were lost for follow-up, so 22 patients were the final study group. Median (25-75%) ATT side-to-side differences between the injured and uninjured sides were 4 (3,5-4)mm preoperatively, 0,75 (0-1)mm 1 year postoperatively, and 0,75 (0-1)mm 5 years after the operation (P<0.001). Median (25-75%) IKDC scores were 44.25 (35.6-55.15), 92.55 (87.08-96.6), and 95.4 (90.8-97.7) points preoperatively and 1 year (P<0.001) and 5 years postoperatively, respectively. Median (25-75%) Lysholm scores were 52 (38.75-64.5), 95.5 (94.75-99.25), and 97.5 (95-99) points preoperatively and 1 year (P<0.001) and 5 years postoperatively, respectively. DISCUSSION: ACLR with TLS might already achieve favourable outcomes 1 year postoperatively, when measured objectively (ATT) and with PROMs. These outcomes persist 5 year postoperatively. LEVEL OF EVIDENCE IV: retrospective cohort study.

In Vitro Testing of 2 Adjustable-Loop Cortical Suspensory Fixation Systems Versus Interference Screw for Anterior Cruciate Ligament Reconstruction.

BACKGROUND: It is not clear whether the mechanical strength of adjustable-loop suspension devices (ALDs) in anterior cruciate ligament (ACL) reconstruction is device dependent and if these constructs are different from those of an interference screw. PURPOSE: To compare the biomechanical differences of 2 types of ALDs versus an interference screw. STUDY DESIGN: Controlled laboratory study. METHODS: ACL reconstruction was performed on porcine femurs and bovine extensor tendons with 3 types of fixation devices: interference screw, UltraButton (UB) ALD, and TightRope (TR) ALD (n = 10 for each). In addition to specimen testing, isolated testing of the 2 ALDs was performed. The loading protocol consisted of 3 stages: preload (static 150 N load for 5 minutes), cyclic load (50-250 N at 1 Hz for 1000 cycles), and load to failure (crosshead speed 50 mm/min). Displacement at different cycles, ultimate failure load, yield load, stiffness, and failure mode were recorded. RESULTS: In specimen testing, displacement of the ALDs at the 1000th cycle was similar (3.42 ± 1.34 mm for TR and 3.39 ± 0.92 mm for UB), but both were significantly lower than that of the interference screw (7.54 ± 3.18 mm) (P < .001 for both). The yield load of the UB (547 ± 173 N) was higher than that of the TR (420 ± 72 N) (P = .033) or the interference screw (386 ± 51 N; P = .013), with no significant difference between the latter 2. In isolated device testing, the ultimate failure load of the TR (862 ± 64 N) was significantly lower than that of the UB (1879 ± 126 N) (P < .001). CONCLUSION: Both ALDs showed significantly less displacement in cyclic loading at ultimate failure than the interference screw. The yield load of the UB was significantly higher than that of the other 2. The ultimate failure occurred at a significantly higher load for UB than it did for TR in isolated device testing. CLINICAL RELEVANCE: Both UB and TR provided stronger fixation than an interference screw. Although difficult to assess, intrinsic differences in the mechanical properties of these ALDs may affect clinical outcomes.

Racial differences in protein S Tokushima and two protein C variants as genetic risk factors for venous thromboembolism.

BACKGROUND: Racial differences in genetic risk factors for venous thromboembolism (VTE) are elucidated, with factor V Leiden and prothrombin G20210A being prevalent among the Caucasian population but rare among non-Caucasians. OBJECTIVES: To assess the worldwide distribution of three gene polymorphisms previously identified as genetic risk factors among East Asian subpopulations: protein S (PS) Tokushima (p.Lys196Glu), protein C (PC) p.Arg189Trp, and PC p.Lys193del. METHODS: An international collaborative study group of seven centers in five countries-Japan, South Korea, Singapore, Hungary, and Brazil-was created, and genotype analyses were performed. A total of 2850 unrelated individuals (1061 patients with VTE and 1789 controls) were included. RESULTS: PS Tokushima was confined to Japanese patients with VTE (allele frequency, 2.35%) and controls (1.12%), with an odds ratio (OR) of 2.15 (95% confidence interval, 1.16-3.99). PC p.Arg189Trp carriers were prevalent among Chinese and Malay patients with VTE in Singapore, with allele frequencies of 10.53% and 22.73%, respectively. Carriers of PC p.Lys193del were identified among Japanese and Korean patients with VTE (0.87% and 2.35%, respectively) and controls (0.36% and 1.07%, respectively), with the OR for VTE not being significant, and Chinese patients with VTE in Singapore (5.26%). In contrast, no carriers of PS Tokushima and two PC gene variants were found among patients with VTE or controls from Hungary, Brazil, or Indians in Singapore. CONCLUSION: The three variants were prevalent among East and Southeast Asians, having some differences in geographic distribution, but were absent among Caucasian subpopulations and Brazilians.

The screening of rare blood donors in a highly admixed population: A new approach for Holley and Diego genotyping and impact of genomic and self-reported ancestry.

OBJECTIVES: The present study aimed to develop strategies for genotyping DO*HY (Dombrock system) and DI*A/DI*B (Diego system) alleles and to evaluate the impact of genomic and self-declared ancestry on rare donor screening in admixed populations. BACKGROUND: The antigens Hy and Dib demonstrate clinical importance. The lack of antisera for the serological evaluation of these antigens makes it necessary to develop molecular methods. In addition, considering that some rare red blood cell phenotypes present differences in frequency between ethnic groups, it is important to assess the applicability of self-declared ancestry in the search for rare donors in admixed populations. METHODS: DO*HY and DI*A/DI*B genotyping based on real-time polymerase chain reaction (PCR) was standardised. A total of 457 blood donors clustered by self-defined skin colour/race categories were genotyped. Furthermore, individual genomic ancestry was used in the analyses. RESULTS: The assays developed are reproducible and provide satisfactory results even at low concentrations of DNA, which make them useful in situations where the DNA is scarce, such as dried blood spots on filter paper, or when screening for pooled samples. No significant difference was observed in the frequencies of the DI*A, DI*B and DO*HY, comparing the self-declared White (branco) donors with those who are Black (preto) and Brown (pardo). CONCLUSION: Real-time PCR, especially using pooled samples, is a promising strategy to screen rare blood donors. Although both self-reported race/colour and some blood group phenotypes are associated with ancestry, the results point to a greater complexity in the application of self-declared race/colour in the screening of rare donors in admixed populations.

A new index to discriminate between iron deficiency anemia and thalassemia trait.

BACKGROUND: The most common microcytic and hypochromic anemias are iron deficiency anemia and thalassemia trait. Several indices to discriminate iron deficiency anemia from thalassemia trait have been proposed as simple diagnostic tools. However, some of the best discriminative indices use parameters in the formulas that are only measured in modern counters and are not always available in small laboratories. The development of an index with good diagnostic accuracy based only on parameters derived from the blood cell count obtained using simple counters would be useful in the clinical routine. Thus, the aim of this study was to develop and validate a discriminative index to differentiate iron deficiency anemia from thalassemia trait. METHODS: To develop and to validate the new formula, blood count data from 106 (thalassemia trait: 23 and iron deficiency: 83) and 185 patients (thalassemia trait: 30 and iron deficiency: 155) were used, respectively. Iron deficiency, ß-thalassemia trait and α-thalassemia trait were confirmed by gold standard tests (low serum ferritin for iron deficiency anemia, HbA2>3.5% for ß-thalassemia trait and using molecular biology for the α-thalassemia trait). RESULTS: The sensitivity, specificity, efficiency, Youden's Index, area under receiver operating characteristic curve and Kappa coefficient of the new formula, called the Matos & Carvalho Index were 99.3%, 76.7%, 95.7%, 76.0, 0.95 and 0.83, respectively. CONCLUSION: The performance of this index was excellent with the advantage of being solely dependent on the mean corpuscular hemoglobin concentration and red blood cell count obtained from simple automatic counters and thus may be of great value in underdeveloped and developing countries.

Lipoxin A4 Is Increased in the Plasma of Preeclamptic Women.

BACKGROUND: Excessive inflammation is involved in preeclampsia (PE) pathogenesis. Lipoxin A4 (LXA4) is an eicosanoid that counter-regulates inflammation. The main objective of this study was to determine LXA4 plasma levels in PE women. The correlations among LXA4 levels, ultrasensitive C-reactive protein (us-CRP) levels, and clinical/laboratory parameters of the studied participants were also investigated. METHODS: LXA4 plasma levels were determined by ELISA in 23 nonpregnant, 26 normotensive pregnant, and 27 PE women (early PE (N = 10) and late PE (N = 17)), according to gestational age (GA) at clinical symptoms onset). The clinical/laboratory parameters included in Spearman's correlation analysis were: systolic and diastolic blood pressure (SBP and DBP, respectively), lactate dehydrogenase (LDH) activity, platelet count, proteinuria, and white blood cell count (WBC). RESULTS: LXA4 levels were higher in PE women than in nonpregnant and normotensive pregnant women, and similar between nonpregnant and normotensive pregnant women. LXA4 plasma levels were higher in early PE vs. normotensive pregnancy (GA < 34 weeks) and in late PE vs. normotensive pregnancy (GA ≥ 34 weeks). No significant differences were detected between early and late PE. LXA4 levels were positively correlated with us-CRP levels, SBP, DBP, and WBC. No significant correlation was detected between LXA4 levels and the other laboratory parameters. CONCLUSIONS: Chronic inflammation in PE, in spite of increased levels of LXA4, points to a possible failure in this regulatory pathway. Further studies are necessary to clarify this issue and to evaluate the role of LXA4 and other proresolving mediators of inflammation in the pathogenesis of PE.

Association between Von Willebrand factor, disintegrin and metalloproteinase with thrombospondin type 1 motif member 13, d-Dimer and cystatin C levels with retinopathy in type 1 diabetes mellitus.

BACKGROUND: We evaluated the association between plasma levels of VWF, ADAMTS13 and d-Dimer, which consist on endothelial dysfunction and hypercoagulability biomarkers, and cystatin C with retinopathy in type 1 diabetic patients. METHODS: Patients were classified according to presence (n=55) or absence (n=70) of retinopathy. Plasma levels of VWF, ADAMTS13, d-Dimer and cystatin C were evaluated by ELISA and ADAMTS13 activity was evaluated by FRET. RESULTS: Plasma levels of VWF (p=0.033), ADAMTS13 activity (p=0.014), d-Dimer (p=0.002) and cystatin C (p<0.001) were elevated in diabetic patients with retinopathy compared to those without this complication. The multivariate logistic regression analysis showed that ADAMTS13 activity (p=0.031) d-Dimer (p=0.015) and cystatin C (p=0.001) remained associated with retinopathy after adjustment for age, diabetes duration, use of statin, use of ACEi or angiotensin antagonist, use of acetylsalicylic acid and glomerular filtration rate. CONCLUSION: ADAMTS13 activity, d-Dimer and cystatin C are associated with retinopathy in type 1 diabetic patients and are promising biomarkers for the diagnosis and monitoring of diabetic retinopathy.

Tissue factor-dependent pathway in severe preeclampsia revisited: a Brazilian cohort study.

Previously we investigated the tissue factor (TF)-dependent coagulation pathway and key haemostatic cofactors in white women with preeclampsia (P-EC) and suggested that plasma factor VII (FVII) levels can differentiate women with P-EC from healthy nonpregnant women or normal pregnant women, at the same trimester, with high sensitivity, specificity, positive and negative predictive values. Here we re-examine the TF-dependent pathway in a large cohort of Brazilian women. A total of 240 women were studied. These included healthy nonpregnant women (n = 79), normotensive pregnant women (n = 80) and women with severe P-EC (n = 81). Commercially available enzyme-linked immunosorbent assays were used to measure plasma FVII, activated factor VII (FVIIa), TF and tissue factor pathway inhibitor (TFPI). All study participants were matched for age. Pregnant women (with/without P-EC) were matched for gestational age and parity. Plasma levels of FVII, FVIIa and TFPI were significantly increased in women with severe P-EC compared with healthy nonpregnant women (P < 0.01) or normotensive pregnant women (P < 0.01). FVIIa was also higher in normotensive pregnant women compared with nonpregnant women (P < 0.01). However, no such significant trends were observed for plasma TF levels (P = 0.074). In conclusion, circulating FVII, FVIIa and TFPI were significantly elevated in women with severe P-EC in the absence of comparable changes in plasma TF levels. The present work is in agreement with our previous report on FVII levels in white women with P-EC. Thus, this lends further support to the notion that plasma FVII levels are potentially valuable diagnostic marker for P-EC, irrespective of ethnicity.

A new index to discriminate between iron deficiency anemia and thalassemia trait

BACKGROUND: The most common microcytic and hypochromic anemias are iron deficiency anemia and thalassemia trait. Several indices to discriminate iron deficiency anemia from thalassemia trait have been proposed as simple diagnostic tools. However, some of the best discriminative indices use parameters in the formulas that are only measured in modern counters and are not always available in small laboratories. The development of an index with good diagnostic accuracy based only on parameters derived from the blood cell count obtained using simple counters would be useful in the clinical routine. Thus, the aim of this study was to develop and validate a discriminative index to differentiate iron deficiency anemia from thalassemia trait. METHODS: To develop and to validate the new formula, blood count data from 106 (thalassemia trait: 23 and iron deficiency: 83) and 185 patients (thalassemia trait: 30 and iron deficiency: 155) were used, respectively. Iron deficiency, ß-thalassemia trait and a-thalassemia trait were confirmed by gold standard tests (low serum ferritin for iron deficiency anemia, HbA2 > 3.5% for ß-thalassemia trait and using molecular biology for the a-thalassemia trait). RESULTS: The sensitivity, specificity, efficiency, Youden's Index, area under receiver operating characteristic curve and Kappa coefficient of the new formula, called the Matos & Carvalho Index were 99.3%, 76.7%, 95.7%, 76.0, 0.95 and 0.83, respectively. CONCLUSION: The performance of this index was excellent with the advantage of being solely dependent on the mean corpuscular hemoglobin concentration and red blood cell count obtained from simple automatic counters and thus may be of great value in underdeveloped and developing countries.

Annexin A1 Is Increased in the Plasma of Preeclamptic Women.

BACKGROUND: Preeclampsia (PE) is a pregnancy disease associated with exacerbated inflammatory response. Annexin A1 (AnxA1) is a glucocorticoid-regulated protein endowed with anti-inflammatory and proresolving properties that has been much studied in various animal models of inflammation but poorly studied in the context of human inflammatory diseases. The main objective of this study was to measure AnxA1 levels in PE women and to compare those levels in normotensive pregnant and non-pregnant women. We evaluated the association among AnxA1, ultrasensitive C reactive protein (us-CRP) and soluble tumor necrosis factor alpha receptor type 1 (sTNF-R1) plasma levels of the study participants. METHODS: This study included 40 non-pregnant, 38 normotensive pregnant and 51 PE women. PE women were stratified in early (N = 23) and late (N = 28) subgroups, according to gestational age (GA) at onset of clinical symptoms. Protein AnxA1 and us-CRP plasma levels were determined by ELISA and immunoturbidimetric assays, respectively. Transcript levels of AnxA1 in peripheral blood mononuclear cells (PBMC) were measured by real time RT-PCR. RESULTS: Increased levels of AnxA1 coincided with higher us-CRP levels in the plasma of PE women. Pregnant women with early PE had higher levels of AnxA1 and us-CRP than normotensive pregnant women with GA <34 weeks. No significant difference was found for AnxA1 and us-CRP, comparing late PE and normotensive pregnant women with GA ≥ 34 weeks. AnxA1 mRNA levels in PBMC were similar among the studied groups. AnxA1 was positively correlated with sTNF-R1, but not with us-CRP. CONCLUSIONS: Our data show that increased AnxA1 levels were associated with a systemic inflammatory phenotype in PE, suggesting AnxA1 deregulation in PE pathogenesis. However, more studies are needed to clarify the role of AnxA1 and other proresolving molecules in the context of the systemic inflammatory response in this intriguing disease.

Severe preeclampsia: association of genes polymorphisms and maternal cytokines production in Brazilian population.

INTRODUCTION: Preeclampsia (PE) is a multi-system disorder of pregnancy characterized by hypertension and proteinuria. Healthy pregnancy is associated with a controlled inflammatory process, which is exacerbated in PE in response to excessive placental stimuli. Gene expression levels can affect inflammation and immune regulation. It is known that differences in cytokine allele frequencies amongst populations may contribute to difference in the incidence of several diseases. OBJECTIVE: The aim of this study was to investigate the frequency of TNF-α, IL-6, IFN-γ and IL-10 genes polymorphisms and their relationship with the cytokines plasma levels in PE. METHODS: A total of 281 women were included in this study; 116 with severe PE, 107 normotensive pregnant and 58 non-pregnant women. Cytokine genotyping was carried out by the polymerase chain reaction. The analyzed polymorphisms were: TNF-α (-308 G→A), IL-10 (-1082 G→A), IL-6 (-174 G→C), and IFN-γ (+874 A→T). Cytokine plasma levels were measured by Cytometric Bead Array method. RESULTS: A higher frequency of the IFN-γ (+874) T/T genotype in severe PE comparing to normotensive pregnant women was found (P<0.001). TNF-α, IL-6 and IFN-γ plasma levels were higher in PE women compared to non-pregnant women (P<0.001; P<0.001; P=0.004). IL-6 and IFN-γ levels were also higher in PE women compared to normotensive pregnant (P<0.001; P=0.010). IL-10 levels were higher in normotensive pregnant women compared to PE (P<0.001). IFN-γ and IL-6 genes polymorphisms influenced the genic expression in PE and normotensive pregnant women, respectively. CONCLUSIONS: These results suggest that IFN-γ seems to play a role in PE occurrence.