Early Desaturation During 6-Minute Walk Test is a Predictor of Mortality in COPD.

BACKGROUND: Oxygen desaturation during exercise is mainly observed in severe cases of chronic obstructive pulmonary disease (COPD) and is associated with a worse prognosis, but little is known about the type of desaturation that causes the greatest risk of mortality. MATERIAL AND METHODS: We studied all of the 6-min walk tests performed periodically at a tertiary hospital over a period of 12 years in patients with moderate or severe COPD. We classified patients as non-desaturators if they did not suffer a drop in oxygen saturation (SpO2 < 88%) during the test, early desaturators if the time until desaturation was < 1 min, and non-early desaturators if it was longer than 1 min. The average length of follow-up per patient was 5.6 years. RESULTS: Of the 319 patients analyzed, 126 non-desaturators, 91 non-early desaturators and 102 early desaturators were identified. The mortality analysis showed that early desaturators had a mortality of 73%, while it was 38% for non-early desaturators and 28% for non-desaturators, with a survival of 5.9 years compared to 7.5 years and 9.6 years, respectively (hazard ratio of 3.50; 95% CI 2.3-5.3; p < 0.0001). CONCLUSIONS: The early desaturation seen in patients with chronic obstructive pulmonary disease is associated with greater mortality and is likely responsible for the poor prognosis shown globally in patients who desaturate. The survival of patients with early desaturation is almost 4 years less with respect to non-desaturators, and they, thus, require closer observation.

Psychosocial impact of the COVID-19 pandemic on patients with inflammatory bowel disease in Spain. A post lockdown reflection.

OBJECTIVES: This multicenter cross-sectional study was conducted to assess the psychosocial impact of COVID-19 on patients with inflammatory bowel disease (IBD) in Spain during lockdown and the first wave of the pandemic. PATIENTS AND METHODS: A self-report questionnaire that integrated the Spanish version of the Depression, Anxiety and Stress Scale-21 items (DASS-21) and the Perceived Stress Questionnaire (PSS) was designed to gather sociodemographic data and information related to the effects of lockdown on the lives of IBD patients. Twelve IBD units invited their patients to answer the anonymous online survey between the 1st July and the 25th August 2020. RESULTS: Of the 693 survey participants with IBD, 67% were women and the mean age was 43 (SD 12). Sixty-one percent had ulcerative colitis, 36% Crohn's disease and 3% indeterminate colitis. DASS-21 scores indicate that during lockdown the estimated prevalence of depression was 11% [95% CI 8.2-13%], anxiety 20% [95% CI 17 to 23%] and stress 18% [95% CI 8.2-13%]. Multivariate analysis showed that the perceived high risk of COVID-19 infection because of having IBD and maladaptation to government measures to reduce the spread of disease doubled the risk of anxiety and stress during lockdown. CONCLUSIONS: In the short-term, lockdown during the COVID-19 pandemic seemed to have an impact on the already affected mental health of our IBD patients in Spain.

Genome-wide association study of asthma exacerbations despite inhaled corticosteroid use.

RATIONALE: Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies. METHODS: A genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 children of European descent treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed. RESULTS: 10 independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10-6). Of those, one variant at the CACNA2D3-WNT5A locus was nominally replicated in Europeans (rs67026078; p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found. CONCLUSIONS: The intergenic region of CACNA2D3 and WNT5A was revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response.

Efficacy of Human Papillomavirus Vaccination 4 Years After Conization for High-Grade Cervical Neoplasia.

OBJECTIVE: The aim of the study was to estimate human papillomavirus (HPV) vaccination efficacy in reducing recurrence risk within 4 years after conization for high-grade cervical neoplasia. MATERIALS AND METHODS: From January 2012 to June 2015, we performed a longitudinal, observational study (case-series study) on patients diagnosed with cervical intraepithelial neoplasia 2-3 neoplasia. Efficacy was estimated by a 95% CI of the relative risk, relative risk reduction, attributable risk, and number needed to treat. Parametric and nonparametric tests were used as appropriate to compare 160 vaccinated with 171 nonvaccinated patients. To estimate the hazard ratio of the vaccinated status, patients were subjected to multivariable analyses based on the Cox proportional hazard model. To compare recurrence-free survival, a Kaplan-Meier model and a log-rank test were applied. RESULTS: The overall recurrence was 9.4% in the nonvaccinated and 2.5% in the vaccinated group (p = .009). Vaccination was associated with a significant decrease in the relative risk (73.5%, 95% CI = 21.8%-90.9%) with a mean number needed to treat of 14 patients per relapse prevented. Although positive conization margins were related to the highest recurrence risk, not being vaccinated independently increased this risk 3.5-fold in a 4-year follow-up (p = .025). Cumulative recurrence-free rates differed significantly between both groups (log-rank test: p = .009). CONCLUSIONS: Our study corroborates the benefits of HPV vaccination, recommends a closer and longer follow-up in nonvaccinated women, and offers a 4-year prognosis for patients undergoing conization for high-grade cervical lesions.

Genome-wide association study of inhaled corticosteroid response in admixed children with asthma.

BACKGROUND: Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response. OBJECTIVE: We aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings. METHODS: A meta-analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10-6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations. RESULTS: A total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10-6 ). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10-3 ) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10-3 ). Additionally, the reported association of the L3MBTL4-ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified. CONCLUSIONS AND CLINICAL RELEVANCE: This study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment.

The COPD Comorbidome in the Light of the Degree of Dyspnea and Risk of Exacerbation.

The BODE group designed a bubble chart, analogous to the solar system, which depicts the prevalence of each disease and its association with mortality and called it a "comorbidome". Although this graph was used to represent mortality and, later, the risk of needing hospital admission, it was not applied to visualize the association between a set of comorbidities and the categories of the GOLD 2017 guidelines, neither according to the degree of dyspnea nor to the risk of exacerbation. For the purpose of knowing to which extent each comorbidity associates with each of the two conditions-most symptomatic group (groups B and D) and highest risk of exacerbation (groups C and D)-we performed a analysis based on the comorbidome. 439 patients were included. Cardiovascular comorbidity (especially cardiac and renal disease) is predominantly observed in patients with a higher degree of dyspnea, whereas bronchial asthma and stroke occur more frequently in subjects at higher risk of exacerbation. This is the first time that the comorbidome is presented based on the categories of the GOLD 2017 document, which we hope will serve as a stimulus for scientific debate.

Health Status in Patients with COPD According to GOLD 2017 Classification: Use of the COMCOLD Score in Routine Clinical Practice.

The COMCOLD score was developed to quantify the impact of comorbidities on health status in patients with chronic obstructive pulmonary disease (COPD). The objective of this study is to evaluate the association between health status in outpatients with COPD according to COMCOLD score and the GOLD 2017 groups according to symptoms (B and D vs. A and C) and exacerbations (C and D vs. A and B). 439 patients were included. The average score was 2.4 ± 3. 48% of cases had a COMCOLD score >0. The most symptomatic patients (B and D vs. A and C) had a higher score: 3 ± 3.3 vs. 1.3 ± 2.1 (p < 0.001), in contrast with the groups with a higher risk of exacerbation (C and D vs. A and B) in which there was no significant difference: 3 ± 3.5 vs. 2.2 ± 3.0 (p = 0.055). The most symptomatic patients (B and D) showed a greater prevalence of depression, peripheral artery disease and heart disease with an adjusted OR of 3.04 [CI95%: 1.36; 6.86], 2.49 [CI95%: 1.17; 5.29], and 4.41 [CI95%: 2.50; 7.75], respectively. Moreover, no relationship was found between the comorbidities defined by the COMCOLD score and the GOLD 2017 groups with the greatest risk of exacerbation (C and D). The greatest effect on health status was found in those patients with COPD belonging to the most symptomatic groups (B and D), with depression, peripheral artery disease, and heart disease being the main comorbidities involved.

A Quantile Analysis of Plateau and Driving Pressures: Effects on Mortality in Patients With Acute Respiratory Distress Syndrome Receiving Lung-Protective Ventilation.

OBJECTIVES: The driving pressure (plateau pressure minus positive end-expiratory pressure) has been suggested as the major determinant for the beneficial effects of lung-protective ventilation. We tested whether driving pressure was superior to the variables that define it in predicting outcome in patients with acute respiratory distress syndrome. DESIGN: A secondary analysis of existing data from previously reported observational studies. SETTING: A network of ICUs. PATIENTS: We studied 778 patients with moderate to severe acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau pressure, and driving pressure evaluated at 24 hours after acute respiratory distress syndrome diagnosis while ventilated with standardized lung-protective ventilation. We derived our model using individual data from 478 acute respiratory distress syndrome patients and assessed its replicability in a separate cohort of 300 acute respiratory distress syndrome patients. Tidal volume and positive end-expiratory pressure had no impact on mortality. We identified a plateau pressure cut-off value of 29 cm H2O, above which an ordinal increment was accompanied by an increment of risk of death. We identified a driving pressure cut-off value of 19 cm H2O where an ordinal increment was accompanied by an increment of risk of death. When we cross tabulated patients with plateau pressure less than 30 and plateau pressure greater than or equal to 30 with those with driving pressure less than 19 and driving pressure greater than or equal to 19, plateau pressure provided a slightly better prediction of outcome than driving pressure in both the derivation and validation cohorts (p < 0.0000001). CONCLUSIONS: Plateau pressure was slightly better than driving pressure in predicting hospital death in patients managed with lung-protective ventilation evaluated on standardized ventilator settings 24 hours after acute respiratory distress syndrome onset.

Age, PaO2/FIO2, and Plateau Pressure Score: A Proposal for a Simple Outcome Score in Patients With the Acute Respiratory Distress Syndrome.

OBJECTIVES: Although there is general agreement on the characteristic features of the acute respiratory distress syndrome, we lack a scoring system that predicts acute respiratory distress syndrome outcome with high probability. Our objective was to develop an outcome score that clinicians could easily calculate at the bedside to predict the risk of death of acute respiratory distress syndrome patients 24 hours after diagnosis. DESIGN: A prospective, multicenter, observational, descriptive, and validation study. SETTING: A network of multidisciplinary ICUs. PATIENTS: Six-hundred patients meeting Berlin criteria for moderate and severe acute respiratory distress syndrome enrolled in two independent cohorts treated with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using individual demographic, pulmonary, and systemic data at 24 hours after acute respiratory distress syndrome diagnosis, we derived our prediction score in 300 acute respiratory distress syndrome patients based on stratification of variable values into tertiles, and validated in an independent cohort of 300 acute respiratory distress syndrome patients. Primary outcome was in-hospital mortality. We found that a 9-point score based on patient's age, PaO2/FIO2 ratio, and plateau pressure at 24 hours after acute respiratory distress syndrome diagnosis was associated with death. Patients with a score greater than 7 had a mortality of 83.3% (relative risk, 5.7; 95% CI, 3.0-11.0), whereas patients with scores less than 5 had a mortality of 14.5% (p < 0.0000001). We confirmed the predictive validity of the score in a validation cohort. CONCLUSIONS: A simple 9-point score based on the values of age, PaO2/FIO2 ratio, and plateau pressure calculated at 24 hours on protective ventilation after acute respiratory distress syndrome diagnosis could be used in real time for rating prognosis of acute respiratory distress syndrome patients with high probability.

A clinical classification of the acute respiratory distress syndrome for predicting outcome and guiding medical therapy*.

OBJECTIVE: Current in-hospital mortality of the acute respiratory distress syndrome (ARDS) is above 40%. ARDS outcome depends on the lung injury severity within the first 24 hours of ARDS onset. We investigated whether two widely accepted cutoff values of PaO2/FIO2 and positive end-expiratory pressure (PEEP) would identify subsets of patients with ARDS for predicting outcome and guiding therapy. DESIGN: A 16-month (September 2008 to January 2010) prospective, multicenter, observational study. SETTING: Seventeen multidisciplinary ICUs in Spain. PATIENTS: We studied 300 consecutive, mechanically ventilated patients meeting American-European Consensus Conference criteria for ARDS (PaO2/FIO2 ≤ 200 mm Hg) on PEEP greater than or equal to 5 cm H2O, and followed up until hospital discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Based on threshold values for PaO2/FIO2 (150 mm Hg) and PEEP (10 cm H2O) at ARDS onset and at 24 hours, we assigned patients to four categories: group I (PaO2/FIO2 ≥ 150 on PEEP < 10), group II (PaO2/FIO2 ≥ 150 on PEEP ≥ 10), group III (PaO2/FIO2 < 150 on PEEP < 10), and group IV (PaO2/FIO2 < 150 on PEEP ≥ 10). The primary outcome was all-cause in-hospital mortality. Overall hospital mortality was 46.3%. Although at study entry, patients with PaO2/FIO2 less than 150 had a higher mortality than patients with a PaO2/FIO2 greater than or equal to 150 (p = 0.044), there was minimal variability in mortality among the four groups (p = 0.186). However, classification of patients in each group changed markedly after 24 hours of usual care. Group categorization at 24 hours provided a strong association with in-hospital mortality (p < 0.00001): group I had the lowest mortality (23.1%), whereas group IV had the highest mortality (60.3%). CONCLUSIONS: The degree of lung dysfunction established by a PaO2/FIO2 of 150 mm Hg and a PEEP of 10 cm H2O demonstrated that ARDS is not a homogeneous disorder. Rather, it is a series of four subsets that should be considered for enrollment in clinical trials and for guiding therapy. A major contribution of our study is the distinction between survival after 24 hours of care versus survival at the time of ARDS onset.

Common variants of NFE2L2 gene predisposes to acute respiratory distress syndrome in patients with severe sepsis.

INTRODUCTION: The purpose of this study was to investigate whether common variants across the nuclear factor erythroid 2-like 2 (NFE2L2) gene contribute to the development of the acute respiratory distress syndrome (ARDS) in patients with severe sepsis. NFE2L2 is involved in the response to oxidative stress, and it has been shown to be associated with the development of ARDS in trauma patients. METHODS: We performed a case-control study of 321 patients fulfilling international criteria for severe sepsis and ARDS who were admitted to a Spanish network of post-surgical and critical care units, as well as 871 population-based controls. Six tagging single-nucleotide polymorphisms (SNPs) of NFE2L2 were genotyped, and, after further imputation of additional 34 SNPs, association testing with ARDS susceptibility was conducted using logistic regression analysis. RESULTS: After multiple testing adjustments, our analysis revealed 10 non-coding SNPs in tight linkage disequilibrium (0.75 ≤ r (2) ≤ 1) that were associated with ARDS susceptibility as a single association signal. One of those SNPs (rs672961) was previously associated with trauma-induced ARDS and modified the promoter activity of the NFE2L2 gene, showing an odds ratio of 1.93 per T allele (95 % confidence interval, 1.17-3.18; p = 0.0089). CONCLUSIONS: Our findings support the involvement of NFE2L2 gene variants in ARDS susceptibility and reinforce further exploration of the role of oxidant stress response as a risk factor for ARDS in critically ill patients.

Does the new staging system proposed for mycosis fungoides and Sézary syndrome provide reliable agreement for T1 and T2 disease?

BACKGROUND: Patch or plaque stages in mycosis fungoides (MF) have different prognoses. The recent staging system proposed for MF discriminates between patches and plaques based upon clinical features. OBJECTIVE: To estimate interdermatologist agreement on the morphological evaluation of MF lesions. METHODS: Twenty-four patients with MF were enrolled. Two dermatologists evaluated every lesion face to face and independently with respect to the patch-plaque status. Cohen's κ was used to determine the rate of agreement. RESULTS: Agreement was 67% with respect to the patch or plaque status [95% confidence interval (CI) = 49-85%; p < 0.001]. Current systemic treatment (56%; p = 0.01) was associated with lower agreement. Younger age at diagnosis [odds ratio (OR) 1.03 (95% CI 1.02-1.05)], younger age at enrolment [OR 1.03 (95% CI 1.02-1.04)] and time on systemic treatment [OR 1.02 (95% CI 1.01-1.04)] were independent risk factors for disagreement (p < 0.001). CONCLUSION: The new system for MF staging carries a significant risk of disagreement regarding patch and plaque subsets.

Comparative study of weekly and three-weekly neoadjuvant carboplatin in triple-negative breast cancer: retrospective analysis in real-world settings.

PURPOSE: Tri-weekly carboplatin is an established neoadjuvant treatment for triple-negative breast cancer, enhancing pathological complete response (pCR) and overall survival. This study explores if weekly carboplatin provides lower toxicity and comparable pCR rates. METHODS/PATIENTS: A retrospective multicenter study (January 2021 to March 2023) compares outcomes of weekly and tri-weekly carboplatin. RESULTS: Among 104 participants, 60% received weekly and 40% tri-weekly treatments. Weekly administration had fewer discontinuations (56.5 vs. 70.7%, p = 0.154). Both schedules exhibited similar overall toxicity (p = 0.087), with slightly higher grade 3-4 toxicity in the tri-weekly group (56.1 vs. 48.4%, p = 0.126). Hematological toxicity was comparable, but the weekly group experienced more diarrhea (p = 0.432) and asthenia (p = 0.012). Weekly treatment correlated with more frequent breast-conserving surgeries (p = 0.004). pCR rates were 50% with weekly and 61% with tri-weekly regimens (p = 0.186). CONCLUSIONS: Weekly carboplatin exhibited comparable toxicity, a trend toward fewer interruptions, and similar pCR rates. Prospective studies are essential for validating these findings.

Improving the Gleason grading accuracy of transrectal ultrasound-guided biopsy.

BACKGROUND: Transrectal ultrasound (TRUS)-guided prostate biopsy is the technique of choice for the assessment of clinical suspicion of prostate cancer (PC) based on abnormal digital rectal examination (DRE) and/or elevated or rising levels of prostate-specific antigen (PSA). PURPOSE: To identify factors involved in TRUS-guided prostate biopsy, which can be modified by radiologists in order to improve Gleason score (GS) accuracy, and to assess the influence of clinical variables. MATERIAL AND METHODS: We carried out a retrospective review of the records of 185 patients with PC treated surgically at our hospital between 2005 and 2008. Biopsy schemes were classified according to the number of cores (≤7, 8-9, 10-11, 12-15) and the needle length (11, 16, 20 mm). Clinical characteristics - age, family history of PC, DRE, PSA levels, and sonographic data - and prostatectomy GS (pGS) were collected. RESULTS: Non-random concordance between biopsy Gleason score (bGS) and pGS was obtained for 36% of patients (P < 0.001). Under- and over-staging were 30% and 4%, respectively. Concordance was correlated with the core number (45% for ≤7, 54% for 8-9, 85% for 10-11, and 80% for 12-15; P < 0.001), but not with the needle length. The concordance rate showed a seven-fold increase when 10-11 cores were obtained (95% CI, 2-18; P < 0.001) compared to those cases in which the core number obtained was ≤7. Among clinical variables, only PSA correlated with concordance, showing an inverse relationship. CONCLUSION: The Gleason correlation values were not improved when 12 or more cores were collected. These values reached a plateau beyond that number of samples. Therefore, when determining treatment strategies, physicians must consider the biopsy scheme used since it has proven to be a predictor of the accuracy of the PC grading system.

Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome.

Mortality is a frequently reported outcome in clinical studies of acute respiratory distress syndrome (ARDS). However, timing of mortality assessment has not been well characterized. We aimed to identify a crossing-point between cumulative survival and death in the intensive care unit (ICU) of patients with moderate-to-severe ARDS, beyond which the number of survivors would exceed the number of deaths. We hypothesized that this intersection would occur earlier in a successful clinical trial vs. observational studies of moderate/severe ARDS and predict treatment response. We conducted an ancillary study of 1580 patients with moderate-to-severe ARDS managed with lung-protective ventilation to assess the relevance and timing of measuring ICU mortality rates at different time-points during ICU stay. First, we analyzed 1303 patients from four multicenter, observational cohorts enrolling consecutive patients with moderate/severe ARDS. We assessed cumulative ICU survival from the time of moderate/severe ARDS diagnosis to ventilatory support discontinuation within 7-days, 28-days, 60-days, and at ICU discharge. Then, we compared these findings to those of a successful randomized trial of 277 moderate/severe ARDS patients. In the observational cohorts, ICU mortality (487/1303, 37.4%) and 28-day mortality (425/1102, 38.6%) were similar (p = 0.549). Cumulative proportion of ICU survivors and non-survivors crossed at day-7; after day-7, the number of ICU survivors was progressively higher compared to non-survivors. Measures of oxygenation, lung mechanics, and severity scores were different between survivors and non-survivors at each point-in-time (p < 0.001). In the trial cohort, the cumulative proportion of survivors and non-survivors in the treatment group crossed before day-3 after diagnosis of moderate/severe ARDS. In clinical ARDS studies, 28-day mortality closely approximates and may be used as a surrogate for ICU mortality. For patients with moderate-to-severe ARDS, ICU mortality assessment within the first week of a trial might be an early predictor of treatment response.

Can Achilles tendinosis be treated effectively with lidocaine and glucose infiltrations, and if so, is the effect lasting? A longitudinal, observational on 27 consecutive patients.

OBJECTIVE: Our aim was to add to the small but growing body of evidence on the effectiveness of ultrasound-guided Achilles intratendinous hyperosmolar dextrose prolotherapy and introduce a novel, preceding step of paratenon hydrodissection with lidocaine in patients with chronic Achilles tendinosis resistant to rehabilitation therapy. METHODS: We conducted a longitudinal, observational study on 27 consecutive patients diagnosed with Achilles tendinosis, in whom conservative treatment, ie, physiotherapy or shock wave therapy, had failed. A 2% lidocaine paratenon anesthesia and hydrodissection was followed by ultrasound-guided, intratendinous injections of 25% glucose every 5 weeks. Visual analogue scales (VAS) were used for pain assessment at rest, for activities of daily living, and after moderate exercise at the begining and at the end of the treatment. Moreover, tendon thickness and vascularisation were recorded at baseline and final treatment consultation. Effectiveness was estimated from scoring and relative pain reduction using a 95% CI. The non-parametric Wilcoxon test and a general linear model for repeated measures were applied. Statistical significance was established as p < 0.05. RESULTS: A median of 5 (1-11) injection consultations per patient were required. Pain scores decreased significantly in all three conditions (p < 0.001). Relative reductions were 75% in pain at rest (95% CI;61-93%), 69% in pain with daily living activities (95% CI; 55-83%), and 70% in pain after moderate exercise (95% CI; 57-84%). Tendon neo-vascularisation was significantly reduced (p < 0.001). We did not observe significant changes in tendon thickness (p = 0.083). CONCLUSIONS: Achilles tendinosis treatment with paratenon lidocaine hydrodissection and subsequent prolotherapy with hyperosmolar glucose solution is safe, effective, inexpensive, and virtually painless with results maintained over time.

Interleukin-1 receptor-associated kinase 3 gene associates with susceptibility to acute lung injury.

Sepsis is the most common cause of acute lung injury (ALI), leading to organ dysfunction and death in critically ill patients. Previous studies associated variants of interleukin-1 receptor-associated kinase genes (IRAKs) with differential immune responses to pathogens and with outcomes during sepsis, and revealed that increased expression levels of the IRAK3 gene were correlated with poor outcomes during sepsis. Here we explored whether common variants of the IRAK3 gene were associated with susceptibility to, and outcomes of, severe sepsis. After our discovery of polymorphism, we genotyped a subset of seven single-nucleotide polymorphisms (SNPs) in 336 population-based control subjects and 214 patients with severe sepsis, collected as part of a prospective study of adults from a Spanish network of intensive care units. Whereas IRAK3 SNPs were not associated with susceptibility to severe sepsis, rs10506481 showed a significant association with the development of ALI among patients with sepsis (P = 0.007). The association remained significant after adjusting for multiple comparisons, population stratification, and clinical variables (odds ratio, 2.50; 95% confidence interval, 1.15-5.47; P = 0.021). By imputation, we revealed three additional SNPs independently associated with ALI (P < 0.01). One of these (rs1732887) predicted the disruption of a putative human-mouse conserved transcription factor binding site, and demonstrated functional effects in vitro (P = 0.017). Despite the need for replication in independent studies, our data suggest that common SNPs in the IRAK3 gene may be determinants of sepsis-induced ALI.

A risk tertiles model for predicting mortality in patients with acute respiratory distress syndrome: age, plateau pressure, and P(aO(2))/F(IO(2)) at ARDS onset can predict mortality.

BACKGROUND: Predicting mortality has become a necessary step for selecting patients for clinical trials and defining outcomes. We examined whether stratification by tertiles of respiratory and ventilatory variables at the onset of acute respiratory distress syndrome (ARDS) identifies patients with different risks of death in the intensive care unit. METHODS: We performed a secondary analysis of data from 220 patients included in 2 multicenter prospective independent trials of ARDS patients mechanically ventilated with a lung-protective strategy. Using demographic, pulmonary, and ventilation data collected at ARDS onset, we derived and validated a simple prediction model based on a population-based stratification of variable values into low, middle, and high tertiles. The derivation cohort included 170 patients (all from one trial) and the validation cohort included 50 patients (all from a second trial). RESULTS: Tertile distribution for age, plateau airway pressure (P(plat)), and P(aO(2))/F(IO(2)) at ARDS onset identified subgroups with different mortalities, particularly for the highest-risk tertiles: age (> 62 years), P(plat) (> 29 cm H(2)O), and P(aO(2))/F(IO(2)) (< 112 mm Hg). Risk was defined by the number of coexisting high-risk tertiles: patients with no high-risk tertiles had a mortality of 12%, whereas patients with 3 high-risk tertiles had 90% mortality (P < .001). CONCLUSIONS: A prediction model based on tertiles of patient age, P(plat), and P(aO(2))/F(IO(2)) at the time the patient meets ARDS criteria identifies patients with the lowest and highest risk of intensive care unit death.

Evaluation of neutropenia secondary to mycophenolate mofetil associated with valganciclovir in liver transplant patients.

OBJECTIVE: Immunosuppressive drugs are necessary to avoid or reduce the risk of rejection of transplanted organs. The immunosuppression generated may result in these patients needing  antibiotics and antivirals to be prescribed to them in conjunction with their immunosuppressants to avoid the risk of infection. This has generated an increase in neutropenia in patients treated with mycophenolate mofetil in combination with valganciclovir. The purpose of this study is to estimate the risk of neutropenia attributable to combination treatment of mycophenolate mofetil with valganciclovir in patients with a transplanted liver. METHOD: This is a retrospective cohort study. It included patients who received a liver transplant between 2012 and 2017 and who were treated with mycophenolate mofetil or with a combination of mycophenolate mofetil and valganciclovir. Minimum follow-up was 100 days posttransplantation. Children under 16 years of age and patients who died during follow-up were excluded. Binary logistic regression analysis was used to determine the association of neutropenia with sex, age, diabetes, creatinine at baseline and at discharge, and concomitant treatment of mycophenolate mofetil with valganciclovir. Relative risk and 95% CI were calculated using logistic regression coefficients. RESULTS: 144 patients were analyzed, 87 were treated with mycophenolate mofetil and 57 received mycophenolate mofetil and valganciclovir together. An overall risk of neutropenia of 37% [95% CI (29- 45)] was observed. The risk was significantly higher in patients who received the combination of mycophenolate mofetil and valganciclovir (56%) than in those treated with mycophenolate mofetil alone (24%), p = 0.001. Binarylogistic-regression analysis revealed that concomitant use of mycophenolate mofetil with valganciclovir was associated with an increased risk of neutropenia: Relative risk = 4.97, 95% CI [2.25-11.00]. CONCLUSIONS: Our study shows that concomitant use of mycophenolate mofetil and valganciclovir increases the risk of neutropenia in patients with a transplanted liver.

Objetivo: Los fármacos inmunosupresores son necesarios para evitar o reducir el riesgo de rechazo de órganos trasplantados. La inmunosupresión generada puede dar lugar a que estos pacientes necesiten recibir antibióticos y antivíricos con los inmunosupresores para evitar el riesgo de infecciones. Esto ha generado un incremento de neutropenia en pacientes tratados conjuntamente con micofenolato de mofetilo y valganciclovir. El objetivo de este estudio es estimar el riesgo de neutropenia atribuible al tratamiento concomitante de micofenolato de ofetilo y valganciclovir en pacientes trasplantados hepáticos.Método: Estudio de cohorte retrospectiva. Se incluyeron pacientes receptores de hígado entre 2012 y 2017 tratados con micofenolato de mofetilo o con la combinación de micofenolato de mofetilo y valganciclovir, con al menos 100 días de seguimiento postrasplante. Se excluyeron menores de 16 años y pacientes fallecidos durante el seguimiento. El análisis de regresión logística binaria se utilizó para determinar la asociación del riesgo de neutropenia con el sexo, edad, diabetes, creatinina basal y al alta, y tratamiento concomitante de micofenolato de mofetilo y valganciclovir. El riesgo relativo y los IC 95% se calcularon mediante los coeficientes de regresión logística.Resultados: Un total de 144 pacientes fueron analizados, 87 se trataron con micofenolato de mofetilo y 57 recibieron conjuntamente micofenolato de mofetilo y valganciclovir, observándose un riesgo de neutropenia del 37%, IC 95% [29-45]. Este riesgo fue significativamente mayor en pacientes que recibieron la combinación de micofenolato de mofetilo y valganciclovir (56%) respecto a los tratados solo con micofenolato de mofetilo (24%), p = 0,001. El análisis de regresión logística binaria reveló que el uso concomitante de micofenolato de mofetilo y valganciclovir se asociaba a un mayor riesgo de neutropenia: riesgo relativo = 4,97, IC 95% [2,25-11,00].Conclusiones: Nuestro estudio demuestra que el uso concomitante de micofenolato de mofetilo y valganciclovir aumenta el riesgo de neutropenia en pacientes trasplantados hepáticos.