Alloantibodies after simultaneous liver-kidney transplant: A story of primary nonfunction, retransplantation, and antibody-mediated rejection.

Simultaneous liver-kidney transplant (SLKT) in the presence of antihuman leukocyte antigen (HLA) donor-specific antibodies (DSA) is a well-accepted practice. Herein, we describe the evolution of alloantibodies in a patient who received an SLKT. The pre-SLKT serum sample showed multiple strong DSA. As expected, all DSA cleared in a sample collected 4 days after the SLKT. Because of the primary nonfunction of the liver in the SLKT, the patient had a second liver transplant 4 days later. An abrupt increase in DSA levels against the kidney was detected 10 days after the second liver transplant. These DSA were refractory to treatment, and the transplanted kidney was lost due to antibody-mediated rejection (AMR). A detailed study of the HLA epitopes recognized by DSA and, after normalization with third-party alloantibodies to address the effect of multiple transfusions and liver allograft neutralization, showed that the elimination of these antibodies depended on the HLA antigens expressed by the transplanted liver cells. The return of DSA after removal of the first transplanted liver was associated with AMR in the transplanted kidney.

Effectiveness of Telemedicine Compared with Standard Care for Patients with Rheumatic Diseases: A Systematic Review.

Objective: The aim of this study was to systematically review the evidence on the effectiveness of telemedicine compared to standard care for patients with rheumatic diseases. Methods: A search was performed in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews; for the gray literature, GREYNET databases and a snowball search were used. MeSH or Emtree terms. Three authors independently selected systematic reviews, randomized controlled trail (RCTs), or non-RCTs with patients with autoimmune or inflammatory rheumatic diseases, where telemedicine was compared with standard care. Effectiveness was measured in terms of disease activity, quality of life, and functional activity. The patients' satisfaction was also measured. The risk of bias was assessed by the Cochrane collaboration tool for RCTs and AMSTAR II for systematic reviews. Results: Four RCTs, one cross-out study, and five systematic reviews were included. The studies were conducted with rheumatoid arthritis patients, and one study involved patients with systematic lupus erythematosus. The interventions mainly involved teleconsultation and telemonitoring, with patient-reported outcomes (PROs) being compared with standard care. Four studies measured the effectiveness of telemedicine using PROs, in which three of the RCTs did not find differences in the clinical outcomes, and one found that telemedicine improved the remission of diseases, functional impairment, and radiographic joint damage progression. Two studies measured patient satisfaction with telemedicine and standard care without a significant difference between the groups. Conclusions: Despite heterogeneity between studies, the findings were remarkably consistent in demonstrating that there was no significant difference between the telemedicine group and the control group in terms of PROs and patient satisfaction. Patients should be offered the option of telemedicine to manage their diseases as part of health-care support. Further research is needed on the effectiveness of telemedicine in the long term for patients with rheumatic diseases.

Rituximab for Inflammatory Myopathies in a Colombian Cohort.

INTRODUCTION/OBJECTIVES: Rituximab (RTX) is a treatment for refractory inflammatory myopathies, such as dermatomyositis (DM) and polymyositis (PM). This study describes the characteristics of patients receiving RTX for myositis in our institution to evaluate its efficacy. METHOD: We collected demographic data from all patients diagnosed with DM or PM who received RTX between 2011 and 2018. Clinical and serological variables (including creatine phosphokinase [CPK] levels) were analyzed. Remission of disease was defined as no evidence of disease activity (active myositis) for longer than a 6-month continuous period while undergoing myositis therapy or no medication. RESULTS: Eighteen patients who had received first-line immunosuppressants were included. Fifteen (83%) had DM, 2 (11%) had PM, 1 had juvenile dermatomyositis, and 14 (77%) were women. All patients received glucocorticoids. Three patients (16.6%) were treated with RTX as monotherapy, and 15 (83.3%) were treated with RTX combined with other immunosuppressants. On average, there were 2 RTX treatment cycles. Improved muscular weakness was found in 13 cases (72%), and improved serum CPK levels were found in 15 cases (83%). Twelve patients (66%) achieved remission. CONCLUSIONS: Most patients experienced an objective improvement, as reflected in their serum CPK values and degree of muscular weakness. This suggests that RTX could be helpful in treating refractory myositis.

Vastly underestimated species richness of Amazonian salamanders (Plethodontidae: Bolitoglossa) and implications about plethodontid diversification.

We present data showing that the number of salamander species in Amazonia is vastly underestimated. We used DNA sequences of up to five genes (3 mitochondrial and 2 nuclear) of 366 specimens, 189 corresponding to 89 non-Amazonian nominal species and 177 Amazonian specimens, including types or topotypes, of eight of the nine recognized species in the region. By including representatives of all known species of Amazonian Bolitoglossa, except for one, and 73% of the currently 132 recognized species of the genus, our dataset represents the broadest sample of Bolitoglossa species, specimens, and geographic localities studied to date. We performed phylogenetic analyses using parsimony with tree-alignment and maximum likelihood (ML) with similarity alignment, with indels as binary characters. Our optimal topologies were used to delimit lineages that we assigned to nominal species and candidate new species following criteria that maximize the consilience of the current species taxonomy, monophyly, gaps in branch lengths, genetic distances, and geographic distribution. We contrasted the results of our species-delimitation protocol with those of Automated Barcode Gap Discovery (ABGD) and multi-rate Poisson Tree Processes (mPTP). Finally, we inferred the historical biogeography of South American salamanders by dating the trees and using dispersal-vicariance analysis (DIVA). Our results revealed a clade including almost all Amazonian salamanders, with a topology incompatible with just the currently recognized nine species. Following our species-delimitation criteria, we identified 44 putative species in Amazonia. Both ABGD and mPTP inferred more species than currently recognized, but their numbers (23-49) and limits vary. Our biogeographic analysis suggested a stepping-stone colonization of the Amazonian lowlands from Central America through the Chocó and the Andes, with several late dispersals from Amazonia back into the Andes. These biogeographic events are temporally concordant with an early land bridge between Central and South America (~10-15 MYA) and major landscape changes in Amazonia during the late Miocene and Pliocene, such as the drainage of the Pebas system, the establishment of the Amazon River, and the major orogeny of the northern Andes.

Duodenal microbiome in patients with or without Helicobacter pylori infection.

BACKGROUND: Intestinal microbiota are recognized as an organ with important physiological functions whose alterations have been associated with common diseases including inflammatory intestinal conditions, malnutrition, type-2 diabetes, and cardiovascular diseases. The composition and function of the microbiota in the distal part of the intestine has been mainly described, while there is limited information on the small intestine microbiota. The objective of the present study was to describe the duodenal microbiome in individuals with dyspepsia in the presence or absence of Helicobacter pylori gastric infection. MATERIALS AND METHODS: Thirty-eight biopsies from the proximal duodenum of uninfected and 37 from H pylori-infected individuals were analyzed. Microbiota composition was assessed by PCR amplification and sequencing of 16S rRNA and ITS genes; sequences were analyzed with QIIME2. RESULTS AND CONCLUSIONS: At the phyla level, Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, and Fusobacteria were predominant in the mucosal associated duodenal microbiota (MAM); at the genera level, we observed the predominance of Ralstonia, Streptococcus, Pseudomonas, Haemophilus, Herbaspirillum, Neisseria, and Veillonella. Microbiota α-diversity was higher in H pylori-infected individuals than in non-infected ones. In terms of ß-diversity metrics, there was a statistically significant difference between groups. Also, relative abundance of Haemophilus, Neisseria, Prevotella pallens, Prevotella 7, and Streptococcus was greater in H pylori-infected patients. In infected patients, several types of H pylori were present in duodenal MAM. Finally, the majority of duodenal samples had fungi sequences; the most common taxa observed were Recurvomyces followed by Ascomycota and Basidiomycota.

Correlation between quantitative and semiquantitative magnetic resonance imaging and histopathology findings in dermatomyositis.

OBJECTIVES: The aim of this study was to compare muscle biopsy findings, as well as clinical and analytical features, with those of magnetic resonance imaging (MRI) studies of muscle in patients with dermatomyositis. METHODS: All patients from the Longitudinal Myopathy Cohort of the Hospital Clínic de Barcelona were prospectively included in the study from 2009 to 2016. MRI images of muscle and fascial oedema were compared with muscle pathology results using both quantitative and semi-quantitative scores. RESULTS: We found a statistically significant association between the inflammatory infiltrate and both muscle (r2=0.54, p=0.001) and fascial oedema (r2=0.54, p<0.001). In addition, muscle oedema was significantly associated with punched-out vacuoles (p=0.04) and muscle enzymes in serum (r2=0.34, p=<0.01 for CK and r2=0.22, p<0.05 for aldolase). The number of treatment drugs received at the time of MRI was inversely associated with the number of muscle inflammatory cells in the biopsy and with both muscle and fascial oedema (all p<0.05). CONCLUSIONS: Key MRI findings correlate with the main features of dermatomyositis muscle biopsy results, suggesting that MRI findings could be used as a surrogate marker of disease activity.

Deceased organ donor screening for human immunodeficiency virus, hepatitis B virus and hepatitis C virus: Discordant serology and nucleic acid testing results.

BACKGROUND: Before the 2014 policy change pertaining to infectious disease screening, many organ procurement organizations (OPOs) were supplementing serologic screening of deceased organ donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), and hepatitis C virus (HCV). The number of seronegative, NAT-positive donors has not been directly measured. METHODS: HIV, HBV, and HCV screening results of 11 229 donor referrals evaluated from 2010 to 2013 were obtained from 3 OPO-affiliated laboratories, capturing 35% of all donors in the United States. Laboratories used either polymerase chain reaction assay or transcription-mediated amplification assay to test 9643 deceased donors by NAT. RESULTS: The NAT results were positive in 21 (0.2%), 1 (0.02%), and 11 (0.1%) donors who were seronegative for HIV, HBV, and HCV, respectively. All discordant HIV-1 results were from one laboratory using a polymrease chain reaction assay. Thirteen of the reactive HIV NAT results in seronegative referrals were repeated and were non-reproducibly positive (NRP). Ten (0.1%), 452 (7.8%), and 197 (2.2%) of HIV-, HBV-, and HCV-seropositive donors, respectively, were negative by NAT. CONCLUSIONS: This study highlights the importance of robust quality assurance to minimize NRP NAT results. NAT may allow for increased utilization of organs from HBV- and HCV-seropositive, NAT-negative donors.

Solvothermal Synthesis and Photocatalytic Activity of BiOBr Microspheres with Hierarchical Morphologies.

BiOBr microspheres with hierarchical morphologies (BiOBr-MicSphe) has potential application in heterogeneous photocatalysis for decontamination of water and air. For this reason, the synthesis, characterization an evaluation of photocatalytic activity of these materials become important. In this article, BiOBr-MicSphe were synthesized using different ranges of reaction temperature (120-200 °C) and reaction time (12 h - 24 h). Samples grown at 145 °C and 18 h showed the higher photocatalytic activity on gallic acid degradation. Morphological properties, chemical composition and structural analysis revealed that sample with higher photocatalytic activity exhibited a microspherical morphology with pure BiOBr tetragonal phase. Besides, adsorption-desorption analysis showed a smaller pore diameter for sample grown at 145 °C and 18 hrs. The results showed that the reaction temperature has a strong influence on the different properties of the material, affecting the photocatalytic activity.

The unusual minimum of sunspot cycle 23 caused by meridional plasma flow variations.

Direct observations over the past four centuries show that the number of sunspots observed on the Sun's surface varies periodically, going through successive maxima and minima. Following sunspot cycle 23, the Sun went into a prolonged minimum characterized by a very weak polar magnetic field and an unusually large number of days without sunspots. Sunspots are strongly magnetized regions generated by a dynamo mechanism that recreates the solar polar field mediated through plasma flows. Here we report results from kinematic dynamo simulations which demonstrate that a fast meridional flow in the first half of a cycle, followed by a slower flow in the second half, reproduces both characteristics of the minimum of sunspot cycle 23. Our model predicts that, in general, very deep minima are associated with weak polar fields. Sunspots govern the solar radiative energy and radio flux, and, in conjunction with the polar field, modulate the solar wind, the heliospheric open flux and, consequently, the cosmic ray flux at Earth.

Outcome-based Risk Assessment of Non-HLA Antibodies in Heart Transplantation: A Systematic Review.

BACKGROUND: Current monitoring after heart transplantation (HT) employs repeated invasive endomyocardial biopsies (EMB). Although positive EMB confirms rejection, EMB fails to predict impending, subclinical, or EMB-negative rejection events. While non-human leukocyte antigen (non-HLA) antibodies have emerged as important risk factors for antibody-mediated rejection after HT, their use in clinical risk stratification has been limited. A systematic review of the role of non-HLA antibodies in rejection pathologies has the potential to guide efforts to overcome deficiencies of EMB in rejection monitoring. METHODS: Databases were searched to include studies on non-HLA antibodies in HT recipients. Data collected included the number of patients, type of rejection, non-HLA antigen studied, association of non-HLA antibodies with rejection, and evidence for synergistic interaction between non-HLA antibodies and donor-specific anti-human leukocyte antigen antibody (HLA-DSA) responses. RESULTS: A total of 56 studies met the inclusion criteria. Strength of evidence for each non-HLA antibody was evaluated based on the number of articles and patients in support versus against their role in mediating rejection. Importantly, despite previous intense focus on the role of anti-major histocompatibility complex class I chain-related gene A (MICA) and anti-angiotensin II type I receptor antibodies (AT1R) in HT rejection, evidence for their involvement was equivocal. Conversely, the strength of evidence for other non-HLA antibodies supports that differing rejection pathologies are driven by differing non-HLA antibodies. CONCLUSIONS: This systematic review underscores the importance of identifying peri-HT non-HLA antibodies. Current evidence supports the role of non-HLA antibodies in all forms of HT rejection. Further investigations are required to define the mechanisms of action of non-HLA antibodies in HT rejection.

Comparison of 10% vs. 30% Velocity Loss during Squat Training with Low Loads on Strength and Sport-Specific Performance in Young Soccer Players.

The aim of this study was to compare the effects of two velocity-based resistance training (RT) programs using moderate loads (45-60% 1RM) but different magnitudes of velocity loss (VL) limits (10% vs. 30%) on the changes in physical performance in young soccer players. Twenty young soccer players were randomly allocated into two groups: VL10% (n = 10) and VL30% (n = 10). All participants were assessed before and after the 8-week RT program (twice a week) involving the following tests: 20 m running sprint (T20), countermovement jump (CMJ), kicking a ball (KB), and progressive loading test in the full squat (SQ) exercise. The RT program was conducted using only the SQ exercise and movement velocity was monitored in all repetitions. Significant 'time × group' interaction (p < 0.05) was observed for sprint performance, KB and 1RM in the SQ exercise in favor of VL10%. No significant changes between groups at post-test were observed. The VL10% resulted in significant (p < 0.05-0.001) intra-group changes in all variables analyzed, except for KB, whereas VL30% only showed significant (p < 0.05) performance increments in a sprint test and 1RM in the SQ exercise. The percentage of change and the intra-group's effect size were of greater magnitude for VL10% in all variables analyzed compared to VL30%. In conclusion, our results suggest that, for non-trained young soccer players, squat training with low to moderate relative loads and 10%VL is sufficient to elicit significant increases in muscle strength and sport-specific actions compared to 30%VL in the set.

Using the dipolar and quadrupolar moments to improve solar-cycle predictions based on the polar magnetic fields.

The solar cycle and its associated magnetic activity are the main drivers behind changes in the interplanetary environment and Earth's upper atmosphere (commonly referred to as space weather and climate). In recent years there has been an effort to develop accurate solar cycle predictions, leading to nearly a hundred widely spread predictions for the amplitude of solar cycle 24. Here we show that cycle predictions can be made more accurate if performed separately for each hemisphere, taking advantage of information about both the dipolar and quadrupolar moments of the solar magnetic field during minimum.

Crossmatch assays in transplantation: Physical or virtual?: A review.

The value of the crossmatch test in assessing pretransplant immunological risk is vital for clinical decisions, ranging from the indication of the transplant to the guidance of induction protocols and treatment with immunosuppressants. The crossmatch tests in transplantation can be physical or virtual, each with its advantages and limitations. Currently, the virtual crossmatch stands out for its sensitivity and specificity compared to the physical tests. Additionally, the virtual crossmatch can be performed in less time, allowing for a reduction in cold ischemia time. It shows a good correlation with the results of physical tests and does not negatively impact graft survival. Proper communication between clinicians and the transplant immunology laboratory will lead to a deeper understanding of each patient's immunological profile, better donor-recipient selection, and improved graft survival.

Study of association between antibodies to non-HLA kidney self-antigens and progression to chronic immune injury after kidney transplantation.

BACKGROUND: Immune response to several kidney self-antigens (KSAg) such as Collagen IV (Col-IV), Perlecan (PL), and Fibronectin (FN) have been associated with antibody-mediated damage and poor allograft survival. Thus, the aim of this study was to determine if humoral immune responses to KSAg correlates with progression of chronic immune injury (CII) changes at 1 year or 2 years. METHODS: Kidney transplant recipients who underwent 1- or 2-year biopsies, with chronic interstitial inflammation (ci > 1) and/or glomerular membrane double contouring (cg > 0) were analyzed with matched controls. Sera were analyzed retrospectively for antibodies against KSAg using ELISA. The presence of antibodies to KSAg were compared at 0, 4, 12, and 24 months using logistic regression. RESULTS: We identified a cohort of 214 kidney transplant recipients. Of these, we identified 33 cases and matched 66 controls. Logistical regression showed an odds ratio of 1 with the confidence interval crossing 1 for the presence of response to KSAg at all the time points. CONCLUSIONS: Humoral immune responses to either KSAg alone or in combination with donor-specific anti-HLA antibodies are not associated with progression to CII at 1 and 2 years after kidney transplantation.

Clinical outcomes and complications of single anastomosis duodenal-ileal bypass with sleeve gastrectomy: A 2-year follow-up study in Bogotá, Colombia.

BACKGROUND: The global prevalence of obesity has increased over the past 40 years, and bariatric surgery has proven to be the most effective therapy for long-term weight loss. Its principles are based on modifying the brain-gut axis by altering the gastrointestinal anatomy and affecting the function of gastrointestinal hormones, thereby modifying satiety signals. Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) combines both techniques and has become an alternative to gastric bypass and biliopancreatic diversion procedures for treating severe obesity and associated metabolic diseases in selected patients. AIM: To describe the outcomes and complications of SADI-S. METHODS: We retrospectively analyzed the data of patients who underwent SADI-S laparoscopically at the Clínica Reina Sofía in Bogotá, Colombia. This study assessed the therapeutic effectiveness of SADI-S in terms of short-term preoperative clinical characteristics, postoperative complications, comorbidities, nutritional defi-ciencies, and intraoperative complications during a 2-year follow-up. RESULTS: Sixty-one patients with a mean body mass index (BMI) of 50 ± 7.1 kg/m2 underwent laparoscopic SADI-S. The mean operative time and hospital stays were 143.8 ± 42 min and 2.3 ± 0.8 d, respectively. The mean follow-up period was 18 mo, and the mean BMI decreased to 28.5 ± 12.2 kg/m2. The excess BMI loss was 41.8% ± 13.5%, and the weight loss percentage was 81.1% ± 17.0%. Resolution of obesity-related comorbidities, including type 2 diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea, was achieved and defined as complete or partial remission. No intraoperative complications were observed. Short-term complications were observed in four (6.8%) patients. However, larger studies with longer follow-up periods are required to draw definitive conclusions. CONCLUSION: SADI-S has a low intraoperative and postoperative complication rate and is effective for weight loss and improving obesity-related comorbidities, including hypertension, type 2 diabetes mellitus, dyslipidemia, and sleep apnea syndrome.

Design and Validation of a Test to Evaluate the Execution Time and Decision-Making in Technical-Tactical Football Actions (Passing and Driving).

Reaction time and decision-making (DMA) in football have usually been evaluated using edited images or videos of game situations. The purpose of this research is to design and validate a test that simultaneously evaluates execution time (ET) and decision-making (DMA) in the subcategories of type of action (TA) and direction of movement (DM). METHODOLOGY: A quantitative, cross-sectional, and descriptive study of 30 young players. A total of 32 stimuli were programmed, corresponding to 64 responses, from which the total index (TI) was obtained from the division between DMA and ET. RESULTS: The content validity index (CVI = 0.78) showed a high degree of consensus among experts. In the validation process, the intraclass correlation coefficient (ICC) was used to assess intraclass and interobserver reliability, and a moderate level of agreement was found between subjects for the TA (ICC = 0.593) and ET (ICC = 0.602) and a moderate high level of concordance for DM (ICC = 0.804) and TI (ICC = 0.855). Regarding interobserver reliability, an excellent level of agreement was found for all variables: TA (ICC = 0.998), DM (ICC = 0.998), ET (ICC = 1.000), and TI (ICC = 1.000). For the relationship between intraobserver and interobserver variables, statistical significance was established as p < 0.01. Finally, the intraobserver ETM (5.40%) and interobserver ETM (0.42%) was low compared with the reference value (5.9%). CONCLUSION: The designed test meets the validity criteria since the variables show sufficient intraclass reliability (test-retest) and reliability among observers.

Scarcity in abundance? Spatial inequalities in Rheumatoid Arthritis in a health system with financial equity.

BACKGROUND: This paper estimates spatial inequalities of Rheumatoid Arthritis (RA) in Colombia and explores correlates of those disparities from a health system perspective. METHODS: We apply descriptive epidemiology to healthcare administrative records for estimation of crude and age-standardized prevalences, and health systems thinking for identification of barriers to effective access in RA diagnosis. RESULTS: The crude and age-standardized RA prevalence for Colombia in 2018 is estimated at 0.43% and 0.36%, respectively. In the contributory regime, the binding constraint is effective access to rheumatologists in rural and sparsely populated areas; this constraint in workforce affects service delivery, and ultimately comes from the lack of a differentiated model for effective provision of healthcare in those areas (governance). CONCLUSIONS: There are opportunities for implementation of public health policies and health system interventions that would lead to a better identification of RA patients and the subsequent more precise estimation of RA prevalence, and most importantly, to reduce exposition to risk factors and accurate diagnosis and treatment of RA patients.

Profiling the Physical Performance of Young Boxers with Unsupervised Machine Learning: A Cross-Sectional Study.

Mexico City is the location with the largest number of boxers in Mexico; in fact, it is the first city in the country to open a Technological Baccalaureate in Education and Sports Promotion with a pugilism orientation. This cross-sectional study aimed to determine the physical-functional profile of applicants for admission to the baccalaureate in sports. A total of 227 young athletes (44F; 183M; 15.65 (1.79) years; 63.66 (14.98) kg; >3 years of boxing experience) participated in this study. Body mass (BM), maximal isometric handgrip (HG) strength, the height of the countermovement jump (CMJ), the velocity of straight boxing punches (PV), and the rear hand punch impact force (PIF) were measured. The young boxers were profiled using unsupervised machine learning algorithms, and the probability of superiority (ρ) was calculated as the effect size of the differences. K-Medoids clustering resulted in two sex-independent significantly different groups: Profile 1 (n = 118) and Profile 2 (n = 109). Except for BM, Profile 2 was statistically higher (p < 0.001) with a clear distinction in terms of superiority on PIF (ρ = 0.118), the PIF-to-BM ratio (ρ = 0.017), the PIF-to-HG ratio (ρ = 0.079) and the PIF-to-BM+HG ratio (ρ = 0.008). In general, strength levels explained most of the data variation; therefore, it is reasonable to recommend the implementation of tests aimed at assessing the levels of isometric and applied strength in boxing gestures. The identification of these physical-functional profiles might help to differentiate training programs during sports specialization of young boxing athletes.