Real-world analysis of main clinical outcomes in patients with polycythemia vera treated with ruxolitinib or best available therapy after developing resistance/intolerance to hydroxyurea.

BACKGROUND: Ruxolitinib is approved for patients with polycythemia vera (PV) who are resistant/intolerant to hydroxyurea, but its impact on preventing thrombosis or disease-progression is unknown. METHODS: A retrospective, real-world analysis was performed on the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to subsequent treatment with ruxolitinib (n = 105) or the best available therapy (BAT; n = 272). Survival probabilities and rates of thrombosis, hemorrhage, acute myeloid leukemia, myelofibrosis, and second primary cancers were calculated according to treatment. To minimize biases in treatment allocation, all results were adjusted by a propensity score for receiving ruxolitinib or BAT. RESULTS: Patients receiving ruxolitinib had a significantly lower rate of arterial thrombosis than those on BAT (0.4% vs 2.3% per year; P = .03), and this persisted as a trend after adjustment for the propensity to have received the drug (incidence rate ratio, 0.18; 95% confidence interval, 0.02-1.3; P = .09). There were no significant differences in the rates of venous thrombosis (0.8% and 1.1% for ruxolitinib and BAT, respectively; P = .7) and major bleeding (0.8% and 0.9%, respectively; P = .9). Ruxolitinib exposure was not associated with a higher rate of second primary cancers, including all types of neoplasia, noncutaneous cancers, and nonmelanoma skin cancers. After a median follow-up of 3.5 years, there were no differences in survival or progression to acute leukemia or myelofibrosis between the 2 groups. CONCLUSIONS: The results suggest that ruxolitinib treatment for PV patients with resistance/intolerance to hydroxyurea may reduce the incidence of arterial thrombosis. LAY SUMMARY: Ruxolitinib is better than other available therapies in achieving hematocrit control and symptom relief in patients with polycythemia vera who are resistant/intolerant to hydroxyurea, but we still do not know whether ruxolitinib provides an additional benefit in preventing thrombosis or disease progression. We retrospectively studied the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to whether they subsequently received ruxolitinib (n = 105) or the best available therapy (n = 272). Our findings suggest that ruxolitinib could reduce the incidence of arterial thrombosis, but a disease-modifying effect could not be demonstrated for ruxolitinib in this patient population.

Cytoreductive treatment in patients with CALR-mutated essential thrombocythaemia: a study comparing indications and efficacy among genotypes from the Spanish Registry of Essential Thrombocythaemia.

The present study assessed the criteria for initiating cytoreduction and response to conventional therapies in 1446 patients with essential thrombocythemia (ET), 267 (17%) of which were CALR-mutated. In low risk patients, time from diagnosis to cytoreduction was shorter in CALR-positive than in the other genotypes (2·8, 3·2, 7·4 and 12·5 years for CALR, MPL, JAK2V617F and TN, respectively, P < 0·0001). A total of 1104 (76%) patients received cytoreductive treatment with hydroxycarbamide (HC) (n = 977), anagrelide (n = 113), or others (n = 14). The estimated cumulative rates of complete haematological response (CR) at 12 months were 40 % and 67% in CALR and JAK2V617F genotypes, respectively. Median time to CR was 192 days for JAK2V617F, 343 for TN, 433 for MPL, and 705 for CALR genotypes (P < 0·0001). Duration of CR was shorter in CALR-mutated ET than in the remaining patients (P = 0·003). In CALR-positive patients, HC and anagrelide had similar efficacy in terms of response rates and duration. CALR-mutated patients developed resistance/intolerance to HC more frequently (5%, 23%, 27% and 15% for JAK2V617F, CALR, MPL and TN, respectively; P < 0·0001). In conclusion, conventional cytoreductive agents are less effective in CALR-mutated ET, highlighting the need for new treatment modalities and redefinition of haematologic targets for patients with this genotype.

In-hospital postoperative infection after heart transplantation: Risk factors and development of a novel predictive score.

INTRODUCTION: Infection is one of the most significant complications following heart transplantation (HT). The aim of this study was to identify specific risk factors for early postoperative infections in HT recipients, and to develop a multivariable predictive model to identify HT recipients at high risk. METHODS: A single-center, observational, and retrospective study was conducted. The dependent variable was in-hospital postoperative infection. We examined demographic and epidemiological data from donors and recipients, surgical features, and adverse postoperative events as independent variables. Backwards, stepwise multivariable logistic regression with a P-value < 0.05 was used to identify clinical factors independently associated with the risk of in-hospital postoperative infections following HT. RESULTS: Six hundred seventy-seven patients were included in this study. During the in-hospital postoperative period, 348 episodes of infection were diagnosed in 239 (35.9%) patients. Seven variables were identified as independent clinical predictors of early postoperative infection after HT: history of diabetes mellitus, previous sternotomy, preoperative mechanical ventilation, primary graft failure, major surgical bleeding, use of mycophenolate mofetil, and use of itraconazole. Based on the results of multivariable models, we constructed a 7-variable (8-point) score to predict the risk of in-hospital postoperative infection in HT recipients, which showed a reasonable ability to predict the risk of in-hospital postoperative infection in this population. Prospective external validation of this new score is warranted to confirm its clinical applicability. CONCLUSIONS: In-hospital postoperative infection is a common complication after HT, affecting 35% of patients who underwent this procedure at our institution. Diabetes mellitus, previous sternotomy, preoperative mechanical ventilation, primary graft failure, major surgical bleeding, use of mycophenolate mofetil, and itraconazole were all independent clinical predictors of early postoperative infection after HT.

Donor Polymorphisms in Genes Related to B-Cell Biology Associated With Antibody-Mediated Rejection After Heart Transplantation.

BACKGROUND: Heart transplantation (HT) is a well-established lifesaving treatment for endstage cardiac failure. Antibody-mediated rejection (AMR) represents one of the main problems after HT because of its diagnostic complexity and the poor evidence for supporting treatments. Complement cascade and B-cells play a key role in AMR and contribute to graft damage. This study explored the importance of variants in genes related to complement pathway and B-cell biology in HT and AMR in donors and in donor-recipient pairs.Methods and Results:Genetic variants in 112 genes (51 complement and 61 B-cell biology genes) were analyzed on next-generation sequencing in 28 donor-recipient pairs, 14 recipients with and 14 recipients without AMR. Statistical analysis was performed with SNPStats, R, and EPIDAT3.1. We identified one single nucleotide polymorphism (SNP) in donors in genes related to B-cell biology,interleukin-4 receptor subunitα (p.Ile75Val-IL4Rα), which correlated with the development of AMR. Moreover, in the analysis of recipient-donor genotype discrepancies, we identified another SNP, in this case inadenosine deaminase(ADA; p.Val178(p=)), which was related to B-cell biology, associated with the absence of AMR. CONCLUSIONS: Donor polymorphisms and recipient-donor discrepancies in genes related to the biology of B-cells, could have an important role in the development of AMR. In contrast, no variants in donor or in donor-recipient pairs in complement pathways seem to have an impact on AMR.

Noninvasive monitoring of acute and chronic rejection in heart transplantation.

PURPOSE OF REVIEW: Recent years have seen advances in the early detection of cardiac graft rejection. RECENT FINDINGS: We review the possibilities offered by tissue Doppler imaging and speckle tracking echocardiography, cardiac magnetic resonance, cardiac computed tomography, single positron emission tomography, gene expression profiling, and quantitation of donor-derived cell-free DNA, and microRNAs. SUMMARY: Noninvasive monitoring of acute and chronic rejection after cardiac transplantation is an unmet need and remains a challenge. Imaging techniques and peripheral blood biomarkers are the most commonly used approaches, and in recent years there has been great progress. Gene expression profiling seems to be useful for ruling out the presence of a moderate to severe acute cellular rejection in stable, low-risk patients. Newer monitoring tools, like donor-derived cell-free DNA or microRNA, seem to be promising for individualizing immunosuppressive therapies and better understanding the mechanisms of rejection.

Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera.

The clinical significance of resistance/intolerance to hydroxycarbamide (HC) was assessed in a series of 890 patients with polycythaemia vera (PV). Resistance/intolerance to HC was recorded in 137 patients (15·4%), consisting of: need for phlebotomies (3·3%), uncontrolled myeloproliferation (1·6%), failure to reduce massive splenomegaly (0·8%), development of cytopenia at the lowest dose of HC to achieve a response (1·7%) and extra-haematological toxicity (9%). With a median follow-up of 4·6 years, 99 patients died, resulting in a median survival of 19 years. Fulfilling any of the resistance/intolerance criteria had no impact on survival but when the different criteria were individually assessed, an increased risk of death was observed in patients developing cytopenia [Hazard ratio (HR): 3·5, 95% confidence interval (CI): 1·5-8·3, P = 0·003]. Resistance/intolerance had no impact in the rate of thrombosis or bleeding. Risk of myelofibrotic transformation was significantly higher in those patients developing cytopenia (HR: 5·1, 95% CI: 1·9-13·7, P = 0·001) and massive splenomegaly (HR: 9·1, 95% CI: 2·3-35·9, P = 0·002). Cytopenia at the lowest dose required to achieve a response was also an independent risk factor for transformation to acute leukaemia (HR: 20·3, 95% CI: 5·4-76·5, P < 0·001). In conclusion, the unified definition of resistance/intolerance to HC delineates a heterogeneous group of PV patients, with those developing cytopenia being associated with an adverse outcome.

Clinical evaluation of rosuvastatin in heart transplant patients with hypercholesterolemia and therapeutic failure of other statin regimens: short-term and long-term efficacy and safety results.

We conducted an observational study of 30 heart transplant recipients with serum low-density lipoprotein cholesterol (LDL-c) >100 mg/dl despite previous statin therapy, who were treated with rosuvastatin 10 mg daily (5 mg in case of renal dysfunction). Serum lipids, creatine phosphokinase (CPK), bilirubin, and hepatic enzymes were prospectively measured 2, 4, and 12 weeks after the initiation of the drug. Clinical outcomes of patients who continued on long-term rosuvastatin therapy beyond this 12-week period were reviewed in February 2015. Over the 12-week period following rosuvastatin initiation, serum levels of total cholesterol (TC) and LDL-c and the ratio TC/high-density lipoprotein cholesterol (HDL-c) decreased steadily (P < 0.001). Average absolute reductions of these three parameters were -48.7 mg/dl, -46.6 mg/dl, and -0.9, respectively. Seventeen (57%) achieved a serum LDL-c < 100 mg/dl. No significant changes from baseline were observed in serum levels of triglycerides, HDL-c, hepatic enzymes, bilirubin, or CPK. Twenty-seven (90%) patients continued on long-term therapy with rosuvastatin over a median period of 3.6 years, with no further significant variation in lipid profile. The drug was suspended due to liver toxicity in 1 (3.3%) patient and due to muscle toxicity in 2 (6.7%) patients. All adverse reactions resolved rapidly after rosuvastatin withdrawal. Our study supports rosuvastatin as a reasonable alternative for heart transplant recipients with hypercholesterolemia and therapeutic failure of other statin regimens.

Decision-making in Nasal Dorsum Reconstruction in Revision Rhinoplasty.

Background: The approach to revision rhinoplasty is a challenge that plastic surgeons often face. The objective of this communication is to describe a surgical algorithm for patients undergoing revision rhinoplasty based on the stability of the nasal dorsum. Methods: The study included 18 patients, six men and 12 women, aged 19-54 years, who had previously undergone rhinoplasty and who visited our clinic to request a new procedure due to unsatisfactory results in those procedures. A surgical algorithm developed by the main author (N.A.) was followed for revision rhinoplasty, and then a validated rhinoplasty outcome evaluation questionnaire was applied 1 year after surgery to assess aesthetic outcomes. Results: The questionnaire was applied to all participants, showing a significant increase in patient satisfaction. Before surgery, a minimum value of six and a maximum of 21 (mean of 12) were found. After revision rhinoplasty following the proposed surgical algorithm, a minimum value of 21 and a maximum of 30 (mean of 29) were found, and this difference was statistically significant (P < 0.001). Conclusions: The surgical algorithm used for nasal dorsum reconstruction in patients undergoing revision rhinoplasty improved patient satisfaction and could be a feasible procedure to approach patients who have previously undergone rhinoplasty.

Connective tissue amyloidosis in patients referred for orthopedic surgery. CONNECT-AMY study. / Amiloidosis del tejido conectivo en pacientes referidos a cirugía ortopédica. Estudio CONNECT-AMY.

INTRODUCTION AND OBJECTIVE: Clinical manifestations secondary to amyloid deposition in connective tissue may allow early detection of amyloidosis. We sought to identify the prevalence of connective tissue amyloidosis in patients undergoing orthopedic surgery and evaluate for cardiac involvement. MATERIAL AND METHODS: Descriptive cross-sectional study that included patients >50 years referred for orthopedic surgery at our center. A sample of the affected connective tissue was taken during the intervention to evaluate the presence of amyloid material. Those with confirmed amyloidosis were further evaluated with complementary tests for cardiac involvement. RESULTS: Forty-eight patients were included. Mean age was 65.4 years and 41.7% were women. The most frequent surgery was supraspinatus tendon rupture (50%). Transthyretin amyloid deposits were detected in 2 patients (4.2%). The absence of variants in the protein gene established the diagnosis of ATTRwt in both cases. None of them presented cardiac involvement. CONCLUSIONS: In this study, 4.2% of patients referred for orthopedic surgery presented transthyretin amyloidosis in the affected connective tissue.

Prognostic value of the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio in cardiac amyloidosis.

INTRODUCTION AND OBJECTIVES: The tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/SPAP) ratio is a noninvasive surrogate of right ventricular to pulmonary circulation that has prognostic implications in patients with heart failure (HF) or pulmonary hypertension. Our purpose was to evaluate the prognostic value of the TAPSE/SPAP ratio in patients with cardiac amyloidosis. METHODS: We used the database of the AMIGAL study, a prospective, observational registry of patients with cardiac amyloidosis recruited in 7 hospitals of the Autonomous Community of Galicia, Spain, from January 1, 2018 to October 31, 2022. We selected patients whose baseline TAPSE/SPAP ratio was calculated with transthoracic echocardiography. Long-term survival and survival free of HF hospitalization were assessed by means of 5 different multivariable Cox regression models. Median follow-up was 680 days. RESULTS: We studied 233 patients with cardiac amyloidosis, among whom 209 (89.7%) had transthyretin type. The baseline TAPSE/SPAP ratio correlated significantly with clinical outcomes. Depending on the multivariable model considered, the adjusted hazard ratios estimated per 0.1mm/mmHg increase of baseline TAPSE/SPAP ratio ranged from 0.76 to 0.84 for all-cause mortality. Similarly, the ratios for all-cause mortality of HF hospitalization ranged from 0.79 to 0.84. The addition of the baseline TAPSE/SPAP ratio to the predictive model of the United Kingdom National Amyloidosis Centre resulted in an increase in Harrell's c-statistic from 0.662 to 0.705 for all-cause mortality and from 0.668 to 0.707 for all-cause mortality or HF hospitalization. CONCLUSIONS: Reduced TAPSE/SPAP ratio is an independent adverse prognostic marker in patients with cardiac amyloidosis.

Prevalence of transthyretin cardiac amyloidosis in patients with heart failure with preserved ejection fraction: the PRACTICA study.

INTRODUCTION AND OBJECTIVES: Transthyretin cardiac amyloidosis (ATTR-CA) is a frequent cause of heart failure with preserved ejection fraction (HFpEF). This study sought to determine the prevalence of ATTR-CA among HFpEF patients in a multicenter nationwide study. METHODS: Consecutive ambulatory or hospitalized patients aged ≥ 50 years with HFpEF and left ventricle hypertrophy ≥ 12mm were studied at 20 Spanish hospitals. Screening for cardiac amyloidosis was initiated according to the usual clinical practice of each center. Positive scintigraphs were centrally analyzed. RESULTS: 422 patients were included, of whom 387 underwent further screening for cardiac amyloidosis. A total of 65 patients (16.8%) were diagnosed with ATTR-CA, none below 75 years. There was an increase of prevalence with age. Of them, 60% were male, with a mean age of 85.3±5.2 years, mean left ventricle ejection fraction of 60.3±7.6% and a mean maximum left ventricle wall thickness of 17.2 [12-25] mm. Most of the patients were New York Heart Association class II (48.4%) or III (46.8%). Besides being older than non-ATTR-CA patients, ATTR-CA patients had higher median NT-proBNP levels (3801 [2266-7132] vs 2391 [1141-4796] pg/mL; P=.003). There was no statistical difference in the prevalence of ATTR-CA by sex (19.7% for men and 13.8% for women, P=.085). A ∼7% (4/56) of the patients exhibited a genetic variant (ATTRv). CONCLUSIONS: This multicenter nationwide study found a prevalence of 16.8%, confirming that ATTR-CA is a significant contributor to HFpEF in male and female patients with left ventricle hypertrophy and more than 75 years.

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.

Introduction and objectives: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies. Methods: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA. Results: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group. Conclusion: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

[Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis]. / Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL).

INTRODUCTION AND OBJETIVES: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease. MATERIAL AND METHODS: One hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations. RESULTS: During a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2). AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). CONCLUSIONS: CA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions.

Prognostic value of response to first-line hydroxyurea according to IPSET stratification in essential thrombocythemia.

Hydroxyurea (HU) constitutes the first-line treatment in most patients with essential thrombocythemia (ET), but criteria for changing therapy are not clearly established. The prognostic value of complete hematological response (CHR) and resistance/intolerance to HU was assessed in 1080 patients from the Spanish Registry of ET, classified according to revised IPSET-Thrombosis stratification (Very low- n = 61, Low- n = 83, Intermediate- n = 261, and High-risk n = 675). With a median therapy duration of 5 years, CHR was registered in 720 (67%) patients (1-year probability 51%) and resistance/intolerance in 219 (20%) patients (5-years probability 13%). After correction by other risk factors, High-risk patients achieving CHR showed a reduced risk of arterial thrombosis (HR: 0.35, 95%CI: 0.2-0.6, p = 0.001) and a trend towards lower risk of venous thrombosis (HR: 0.45, 95%CI: 0.2-1.02, p = 0.06) whereas no association was observed for intermediate- or low-risk patients. In comparison with non-responders, intermediate- and high-risk patients achieving CHR had longer survival and lower myelofibrosis incidence. Development of resistance/intolerance to HU, mainly cytopenia, was associated with higher probability of myelofibrosis but no effect on survival or thrombotic risk was demonstrated. In conclusion, CHR with HU is associated with better outcomes and might be an early indicator for selecting candidates to second-line clinical trials.

Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response: The Multicenter ENACT-HF Study.

BACKGROUND: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload. METHODS: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms. RESULTS: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P<0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P<0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P<0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P=0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P=0.852). CONCLUSIONS: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.

Preservation Rhinoplasty: A New Approach to Mestizo Noses.

Preservation rhinoplasty is a widely used technique; however, its use on mestizo noses is poorly documented. Our objective was to assess the level of satisfaction of our mestizo patients 1 year after their preservation rhinoplasty. Methods: The Rhinoplasty Outcome Evaluation (ROE), a Likert-type questionnaire validated in Spanish, was used to assess the level of satisfaction of 14 mestizo patients who underwent preservation rhinoplasty from March to July 2021 at 1 year after their surgery at the Higuereta Clinic in Lima, Peru. Results: The study included 14 patients, three men and 11 women, who underwent preservation rhinoplasty. A presurgical ROE questionnaire was applied, presenting a minimum value of 6, a maximum value of 21, and a mean of 12. When applied 1 year after surgery, the same ROE questionnaire presented a minimum value of 28, a maximum value of 30, and a mean of 30. The variation had a minimum value of 9 and a maximum value of 23, with a mean of 17 (P < 0.001). Conclusions: Preservation rhinoplasty can be successfully implemented in mestizo noses with good aesthetic results.

Soluble HLA-G levels in heart transplant recipients: Dynamics and correlation with clinical outcomes.

PURPOSE: To describe the evolution of the serum levels of soluble HLA-G (s-HLA-G) during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes. METHODS: Observational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. Soluble HLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of s-HLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of s-HLA-G levels over time and correlated with the acute rejection burden -as assessed by a rejection score-, the presence of coronary allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year; as well as with long-term patient and graft survival. Mean follow-up was 12.4 years. RESULTS: Soluble HLA-G levels decreased over the first post-transplant year (p = 0.020). The AUC of s-HLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV. Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of s-HLA-G levels higher or lower than the median of the study population. CONCLUSIONS: Soluble HLA-G levels decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival.