Primary Sclerosing Cholangitis: Gender Effects in Valencia's Low-Prevalence Region.

BACKGROUND AND AIMS: Recent studies point out to epidemiological changes in primary sclerosing cholangitis (PSC). Our aims were to determine in PSC patients followed in several centers in a Mediterranean geographic area: (i) changes in baseline features and (ii) effect of gender on clinical course. METHODS: Retrospective multicenter study of PSC patients treated in 8 hospitals in a Mediterranean area between 2000 and 2021. Charts were reviewed compiling demographic, clinical, radiological, and histological variables. RESULTS: Cohort of 112 PSC patients included, 42% women, 70% diagnosed after 2010. Women were increasingly diagnosed in recent cohorts. The median time from diagnosis to the combined endpoint liver transplantation (Lt) and/or death was 6.9 years. Asthenia at diagnosis (p = 0.009) was associated with lower transplant-free survival, while diagnosis before 2005 was associated with greater LT-free survival (p < 0.001). By Cox regression, LT-free survival was not influenced by age, sex, or cirrhosis at the time of diagnosis. Women were found to have less jaundice at diagnosis (2 vs 14%; p = 0.013), higher prevalence of ANA antibodies (43.9 vs 15.7%; p = 0.003), and lower GGT levels at diagnosis (GGT 123 vs 209U/L; p = 0.014) than men. CONCLUSION: In an area traditionally considered to have low prevalence, the prevalence of affected women surpasses expectations based on existing literature. There appear to be gender-related variations in the presentation of the condition, highlighting the need for confirmation through larger-scale studies.

Characterization of drug-induced liver injury associated with drug reaction with eosinophilia and systemic symptoms in two prospective DILI registries.

Idiosyncratic drug-induced liver injury (DILI) associated with drug reactions with eosinophilia and systemic symptoms (DRESS) is poorly characterized among patients of Western countries. We aimed to comprehensively assess the clinical characteristics, outcomes, and causative agents in a prospective, well-vetted cohort of DILI patients with DRESS (DILI-DRESS). We identified 53 DILI-DRESS cases from the Spanish DILI Registry and the Latin American DILI Network. For comparison purposes, we defined a group of DILI patients (n = 881). DILI-DRESS cases were younger (47 vs. 53 years, respectively; p = 0.042) and presented more frequently with cholestatic/mixed damage (p = 0.018). Most DILI-DRESS patients showed moderate liver injury, 13% developed severe damage, and only one patient (with hepatocellular injury due to anti-tuberculosis drugs) progressed to acute liver failure and died. DILI-DRESS cases showed a distinctive causative drug pattern compared to DILI cases. The most frequent drugs were carbamazepine (13%), anti-tuberculosis drugs (13%), amoxicillin-clavulanate (11%), and allopurinol and lamotrigine (7.6% each). Among all cases of DILI due to allopurinol and lamotrigine, 67% presented with a DILI-DRESS phenotype, respectively. Higher total bilirubin (TBL) levels at DILI recognition (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.04-1.45) and absence of eosinophilia (OR 8.77; 95% CI 1.11-69.20) increased the risk for developing a severe-fatal injury in DILI-DRESS patients. DILI-DRESS patients have a more frequent cholestasis/mixed pattern of injury at presentation, with antiepileptics as distinctive causative drug class. Most of the lamotrigine and allopurinol cases present with this phenotype. Higher TBL levels and absence of eosinophilia at DILI recognition are markers of poor outcomes.

Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries.

BACKGROUND & AIMS: Idiosyncratic drug-induced liver injury (DILI) with autoimmune features is a liver condition with laboratory and histological characteristics similar to those of idiopathic autoimmune hepatitis (AIH), which despite being increasingly reported, remains largely undefined. We aimed to describe in-depth the features of this entity in a large series of patients from two prospective DILI registries. METHODS: DILI cases with autoimmune features collected in the Spanish DILI Registry and the Latin American DILI Network were compared with DILI patients without autoimmune features and with an independent cohort of patients with AIH. RESULTS: Out of 1,426 patients with DILI, 33 cases with autoimmune features were identified. Female sex was more frequent in AIH patients than in the other groups (p = .001). DILI cases with autoimmune features had significantly longer time to onset (p < .001) and resolution time (p = .004) than those without autoimmune features. Interestingly, DILI patients with autoimmune features who relapsed exhibited significantly higher total bilirubin and transaminases at onset and absence of peripheral eosinophilia than those who did not relapse. The likelihood of relapse increased over time, from 17% at 6 months to 50% 4 years after biochemical normalization. Statins, nitrofurantoin and minocycline were the drugs most frequently associated with this phenotype. CONCLUSIONS: DILI with autoimmune features shows different clinical features than DILI patients lacking characteristics of autoimmunity. Higher transaminases and total bilirubin values with no eosinophilia at presentation increase the likelihood of relapse in DILI with autoimmune features. As the tendency to relapse increases over time, these patients will require long-term follow-up.

Utilidad de la ecografía de la arteria femoral complementaria a la exploración carotídea para la detección de ateromatosis subclínica en pacientes con infección por el virus de la inmunodeficiencia humana / Usefulness of artery femoral ultrasound complementary to carotid exploration for the detection of subclinical atheromatosis in patients with human immunodeficiency virus infection

Introducción La detección de la enfermedad ateromatosa subclínica (EAS) en los pacientes con el virus de la inmunodeficiencia humana (VIH) se basa habitualmente en la ecografía carotídea. Sin embargo, estudios en otras enfermedades muestran una infraestimación de la EAS cuando se explora exclusivamente la región carotídea. Este estudio evalúa el impacto de la exploración combinada carotídea y femoral en la detección de la EAS. Métodos Estudio transversal y prospectivo de pacientes con VIH, diagnosticados entre 2008 y 2017. Se realizó ecografía carotídea y femoral. La EAS fue definida según los criterios de Mannheim. Resultados Se incluyeron 102 pacientes (edad media: 40 años, el 73,5% varones). La prevalencia de la EAS por exploración carotídea fue del 15,7% (n=16), y por exploración femoral fue del 18,6% (n=19). La proporción de pacientes con criterios de EAS global (afectación carotídea o femoral) fue del 23,5% (n=24) lo que implica un aumento absoluto de la detección de EAS del 7,84% (IC 95%: 2,63-13,06%). Conclusiones La detección de la EAS aumenta de forma importante con el uso combinado de la ecografía carotídea y femoral en la población con VIH. (AU)

Introduction Detection of subclinical atheromatosis disease (SAD) in patients with human immunodeficiency virus (HIV) infection is usually based on carotid ultrasound. However, studies in other pathologies have shown a probable underestimation of SAD when its detection is exclusively based on carotid exploration. This study evaluates the impact on detection of SAD in patients with HIV through combined carotid and femoral exploration. Methods Cross-sectional and prospective study of patients with HIV, diagnosed between 2008-2017. Carotid and femoral ultrasound examination was performed in all patients. EAS was defined according to Mannheim criteria. Results One hundred two patients were included (mean age: 40 years, 73.5% being male). The prevalence of carotid SAD in the total sample was 15.7% (n=16), and the prevalence of femoral SAD was 18.6% (n=19). The proportion of patients with global SAD criteria (carotid or femoral) was 23.5% (n=24), which implies an absolute increase in SAD detection of 7.84% (95% CI; 2.63-13.06%) at the total sample. Conclusions Detection of SAD is significantly increased by the combined use of carotid and femoral arterial ultrasound in the population affected by HIV infection. (AU)

Bloodstream Infection in Children With Epidermolysis Bullosa.

BACKGROUND: Epidermolysis bullosa (EB) is frequently complicated by skin infection, which can lead to bacteremia. However, bloodstream infections (BSI) in patients with EB have not been well described. METHODS: Retrospective study of BSI in children 0-18 years with EB from a national reference unit in Spain, in 2015-2020. RESULTS: Among 126 children with EB, we identified 37 BSI episodes in 15 patients (14 recessive dystrophic EB, 1 junctional EB). The most frequent microorganisms were Pseudomonas aeruginosa (n = 12) and Staphylococcus aureus (n = 11). Five P. aeruginosa isolates were ceftazidime-resistant (42%), 4 of which were also resistant to meropenem and quinolones (33%). As for S. aureus , 4 (36%) were methicillin-resistant and 3 (27%) clindamycin-resistant. In 25 (68%) BSI episodes skin cultures had been performed in the previous 2 months. The most frequent isolates were also P. aeruginosa (n = 15) and S. aureus (n = 11). In 13 cases (52%), smear and blood cultures grew the same microorganism, with the same antimicrobial resistance pattern in 9 isolates. Twelve patients (10%) died during follow-up (9 RDEB and 3 JEB). BSI was the cause of death in 1 case. In patients with severe RDEB, a history of BSI was associated with higher mortality (OR 6.1, 95% CI: 1.33-27.83, P = 0.0197). CONCLUSIONS: BSI is an important cause of morbidity in children with severe forms of EB. The most frequent microorganisms are P. aeruginosa and S. aureus , with high rates of antimicrobial resistance. Skin cultures can help guide treatment decisions in patients with EB and sepsis.

[Usefulness of artery femoral ultrasound complementary to carotid exploration for the detection of subclinical atheromatosis in patients with human immunodeficiency virus infection]. / Utilidad de la ecografía de la arteria femoral complementaria a la exploración carotídea para la detección de ateromatosis subclínica en pacientes con infección por el virus de la inmunodeficiencia humana.

INTRODUCTION: Detection of subclinical atheromatosis disease (SAD) in patients with human immunodeficiency virus (HIV) infection is usually based on carotid ultrasound. However, studies in other pathologies have shown a probable underestimation of SAD when its detection is exclusively based on carotid exploration. This study evaluates the impact on detection of SAD in patients with HIV through combined carotid and femoral exploration. METHODS: Cross-sectional and prospective study of patients with HIV, diagnosed between 2008-2017. Carotid and femoral ultrasound examination was performed in all patients. EAS was defined according to Mannheim criteria. RESULTS: One hundred two patients were included (mean age: 40 years, 73.5% being male). The prevalence of carotid SAD in the total sample was 15.7% (n=16), and the prevalence of femoral SAD was 18.6% (n=19). The proportion of patients with global SAD criteria (carotid or femoral) was 23.5% (n=24), which implies an absolute increase in SAD detection of 7.84% (95% CI; 2.63-13.06%) at the total sample. CONCLUSIONS: Detection of SAD is significantly increased by the combined use of carotid and femoral arterial ultrasound in the population affected by HIV infection.

Budesonide as first-line treatment in patients with autoimmune hepatitis seems inferior to standard predniso(lo)ne administration.

BACKGROUND AND AIMS: In patients with non-severe acute or chronic autoimmune hepatitis (AIH) without cirrhosis, clinical practice guidelines recommend indistinct use of prednisone or budesonide. However, budesonide is infrequently used in clinical practice. We aimed to describe its use and compare its efficacy and safety with prednisone as first-line options. APPROACH AND RESULTS: This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone. Efficacy was assessed using logistic regression and validated using inverse probability of treatment weighting propensity score. The median time to biochemical response (BR) was 3.1 months in patients treated with budesonide and 4.9 months in those with prednisone. The BR rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). The probability of achieving BR, assessed using the inverse probability of treatment weighting propensity score, was significantly lower in the budesonide group (OR = 0.20; 95% CI: 0.11-0.38) at any time during follow-up, and at 6 (OR = 0.51; 95% CI: 0.29-0.89) and 12 months after starting treatment (0.41; 95% CI: 0.23-0.73). In patients with transaminases <2 × upper limit of normal, BR was similar in both treatment groups. Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%, p = 0.047). CONCLUSIONS: In the real-life setting, the use of budesonide as first-line treatment is low, and it is generally prescribed to patients with perceived less disease activity. Budesonide was inferior to prednisone as a first-line drug but was associated with fewer side effects.

[Capillaroscopy, microangiopathy, and HIV. Descriptive study of capillaroscopy findings in HIV positive patients].

BACKGROUND: In this study, we aim to evaluate microangiopathy in HIV positive patients by using capillaroscopy. To date, few studies have been published on the topic. Capillaroscopy may be a tool for early diagnosis of cardiovascular involvement in this patient population. METHODOLOGY: Cross-sectional study with HIV positive patients >18 years. The enrolment period was set from January to June 2018. The following data were collected: demographic (sex, age), laboratory tests (duration of infection, CD4 cell count, CD4:CD8 ratio, coinfection with other viruses), antiretroviral treatment, dyslipidemia, and comorbidities (active smoking, alcoholism, high blood pressure, dyslipidaemia, diabetes, cardiopathy). The capillaroscopy and blood tests were performed simultaneously. The following alterations were evaluated in the capillaroscopy: congestion, tortuosity, haemorrhage, dilations, capillary loss, and presence of megacapillaries. RESULTS: One hundred and two patients were included; 73.5% were male, mean age was 40 years (SD: 10), and mean duration of infection 4.5 years (SD: 3.1). At diagnosis, mean CD4 cell count was 408/mm3 and CD4/CD8 ratio 0.4. A number of patients (14.7%) were coinfected with the hepatitis B virus; 31.3% were active smokers and 13.7% alcoholics. Capillaroscopy alterations were found in most study patients (93.1%): congestion (78.5%), tortuosity (77.5%), haemorrhage (13.8%), dilations (11.8%), capillary loss (5%), and megacapillaries (1%). Capillary tortuosity was associated with age and smoking; and haemorrhage with age, CD4, antiretroviral treatment, and hypertension. CONCLUSION: Prevalence of capillaroscopy alterations is high in HIV positive patients, particularly tortuosity and congestion. To the best of our knowledge, the later alteration has not been previously reported in this group of patients.

Capilaroscopia, microangiopatía y VIH. Estudio descriptivo de hallazgos capilaroscópicos en pacientes con VIH / Capillaroscopy, microangiopathy, and HIV. Descriptive study of capillaroscopy findings in HIV positive patients

Fundamento: El objetivo de este estudio fue valorar la afectación microangiopática mediante capilaroscopia en pacientes infectados por el virus de la inmunodeficiencia humana (VIH). Apenas ha sido estudiada y podría constituir una herramienta de diagnóstico precoz de afectación cardiovascular en estos pacientes. Material y métodos: Estudio transversal que incluyó pacientes mayores de 18 años, diagnosticados de infección por VIH entre 2008 y 2018. Se recogieron variables demográficas (sexo, edad), analíticas (tiempo de infección, CD4, CD4/CD8, coinfección por otros virus), tratamiento antirretroviral y comorbilidades (tabaquismo, enolismo, hipertensión arterial, dislipemia, diabetes, cardiopatía). Se realizó una capilaroscopia y un análisis de sangre en el mismo acto. Las alteraciones capilaroscópicas evaluadas fueron: congestión, tortuosidades, hemorragias, dilataciones, pérdida capilar y megacapilares. Resultados: Se incluyeron 102 pacientes, 73,5% hombres, edad media 40 años (DE: 10) y tiempo medio de infección 4,5 años (DE: 3,1). Al diagnóstico, la media de CD4 fue 408 células/mm3 y la razón CD4/CD8 fue 0,4. El 14,7% presentaban coinfección por el virus de la hepatitis B, el 31,3% tabaquismo y el 13,7% enolismo. El 93,1% de pacientes mostró alguna alteración capilaroscópica. Se observaron, por orden de frecuencia, congestión (78,5%), tortuosidades (77,5%), hemorragias (13,8%), dilataciones (11,8%), pérdida capilar (5%) y megacapilares (1%). Las torutuosidades se asociaron a edad y tabaquismo, y las hemorragias a edad, CD4, tratamiento antirretroviral, e hipertensión. Conclusiones: Los pacientes con infección por VIH presentan una prevalencia importante de alteraciones capilaroscópicas, principalmente tortuosidades y congestión. Es la primera descripción de áreas de congestión como hallazgo capilaroscópico en este grupo de pacientes.(AU)

Background: In this study, we aim to evaluate microangiopathy in HIV positive patients by using capillaroscopy. To date, few studies have been published on the topic. Capillaroscopy may be a tool for early diagnosis of cardiovascular involvement in this patient population. Methodology: Cross-sectional study with HIV positive patients >18 years. The enrolment period was set from January to June 2018. The following data were collected: demographic (sex, age), laboratory tests (duration of infection, CD4 cell count, CD4:CD8 ratio, coinfection with other viruses), antiretroviral treatment, dyslipidemia, and comorbidities (active smoking, alcoholism, high blood pressure, dyslipidaemia, diabetes, cardiopathy). The capillaroscopy and blood tests were performed simultaneously. The following alterations were evaluated in the capillaroscopy: congestion, tortuosity, haemorrhage, dilations, capillary loss, and presence of megacapillaries. Results: One hundred and two patients were included; 73.5% were male, mean age was 40 years (SD: 10), and mean duration of infection 4.5 years (SD 3.1). At diagnosis, mean CD4 cell count was 408/mm3 and CD4/CD8 ratio 0.4. A number of patients (14.7%) were coinfected with the hepatitis B virus; 31.3% were active smokers and 13.7% alcoholics. Capillaroscopy alterations were found in most study patients (93.1%): congestion (78.5%), tortuosity (77.5%), haemorrhage (13.8%), dilations (11.8%), capillary loss (5%), and megacapillaries (1%). Capillary tortuosity was associated with age and smoking; and haemorrhage with age, CD4, antiretroviral treatment, and hypertension. Conclusion. Prevalence of capillaroscopy alterations is high in HIV positive patients, particularly tortuosity and congestion. To the best of our knowledge, the later alteration has not been previously reported in this group of patients.(AU)

Ertapenem neurotoxicity in liver transplantation.

Carbapenems are antibiotics of the cephalosporin family with a good penetrance into the central nervous system. Neurotoxicity is a rare adverse effect, most often associated with imipenem (0.4-10 %) and unusual with ertapenem. It usually presents as seizures, although encephalopathy or hallucinations may develop. However, a recent large study (n = 544) found neurotoxicity associated to the use of ertapenem with an incidence of 4.6 %. There were associated factors such as advanced age or renal dysfunction (ertapenem has a renal metabolism level of 80 %).

Interlaboratory Analytical Validation of a Next-Generation Sequencing Strategy for Clonotypic Assessment and Minimal Residual Disease Monitoring in Multiple Myeloma.

CONTEXT.­: Minimal residual disease (MRD) is a major prognostic factor in multiple myeloma, although validated technologies are limited. OBJECTIVE.­: To standardize the performance of the LymphoTrack next-generation sequencing (NGS) assays (Invivoscribe), targeting clonal immunoglobulin rearrangements, in order to reproduce the detection of tumor clonotypes and MRD quantitation in myeloma. DESIGN.­: The quantification ability of the assay was evaluated through serial dilution experiments. Paired samples from 101 patients were tested by LymphoTrack, using Sanger sequencing and EuroFlow's next-generation flow (NGF) assay as validated references for diagnostic and follow-up evaluation, respectively. MRD studies using LymphoTrack were performed in parallel at 2 laboratories to evaluate reproducibility. RESULTS.­: Sensitivity was set as 1.3 tumor cells per total number of input cells. Clonality was confirmed in 99% and 100% of cases with Sanger and NGS, respectively, showing great concordance (97.9%), although several samples had minor discordances in the nucleotide sequence of rearrangements. Parallel NGS was performed in 82 follow-up cases, achieving a median sensitivity of 0.001%, while for NGF, median sensitivity was 0.0002%. Reproducibility of LymphoTrack-based MRD studies (85.4%) and correlation with NGF (R2 > 0.800) were high. Bland-Altman tests showed highly significant levels of agreement between flow and sequencing. CONCLUSIONS.­: Taken together, we have shown that LymphoTrack is a suitable strategy for clonality detection and MRD evaluation, with results comparable to gold standard procedures.

Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes.

Drug-induced liver injury (DILI) is an adverse toxic hepatic clinical reaction associated to the administration of a drug that can occur both at early clinical stages of drug development, as well after normal clinical usage of approved drugs. Because of its unpredictability and clinical relevance, it is of medical concern. Three DILI phenotypes (hepatocellular, cholestatic, and mixed) are currently recognized, based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values. However, this classification lacks accuracy to distinguish among the many intermediate mixed types, or even to estimate the magnitude and progression of the injury. It was found desirable to have additional elements for better evaluation criteria of DILI. With this aim, we have examined the serum metabolomic changes occurring in 79 DILI patients recruited and monitored using established clinical criteria, along the course of the disease and until recovery. Results revealed that free and conjugated bile acids, and glycerophospholipids were among the most relevant metabolite classes for DILI phenotype characterization. Using an ensemble of PLS-DA models, metabolomic information was integrated into a ternary diagram to display the disease phenotype, the severity of the liver damage, and its progression. The modeling implemented and the use of such compiled information in an easily understandable and visual manner facilitates a straightforward DILI phenotyping and allow to monitor its progression and recovery prediction, usefully complementing the concise information drawn out by the ALT and ALP classification.

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry.

BACKGROUND & AIMS: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. METHODS: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. RESULTS: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%). CONCLUSIONS: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management. LAY SUMMARY: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes.

Potentially inappropriate prescriptions and therapeutic complexity in older HIV patients with comorbidities.

BACKGROUND: The prolonged current survival of human immunodeficiency virus (HIV) patients exposes them to new problems arising from the comorbidities they face. OBJECTIVES: To describe the situation of comorbidities, polypharmacy, therapeutic complexity and adherence in people living with HIV over 65 years of age and to assess the presence of potentially inappropriate prescriptions (PIP) by applying deprescription criteria. METHODS: Observational study including HIV people (> 65 years) from a university tertiary level hospital. Demographic, clinical and pharmacotherapeutic characteristics of the patients and their treatments were studied. The prevalence of polypharmacy (> 5 medications) and the pharmacotherapy complexity, quantified by the Medication Regimen Complexity Index (MRCI), were calculated. Therapeutic adherence was assessed by the Simplified Medication Adherence Questionnaire (SMAQ) and the medication possession ratio, according to prescription dispensing records. The Screening Tool of Older People's Prescriptions (STOPP) and List of Evidence-baSed depreScribing for CHRONic patients (LESS-CHRON) criteria were applied to identify PIP. MAIN OUTCOME MEASURE: PIP in elderly people living with HIV. RESULTS: Thirty patients were included, 73% of whom were men, with a median age of 71 years (IQR 67 - 76) and a median duration of infection of 17 years (IQR, 9 - 21). Seventy percent of the patients suffered from dyslipemia, 66.7% from hypertension, 43.3% from diabetes and 26.7% from mental health disorders. Seventy percent of the patients took more than 5 medications and 30% more than 10. The MRCI of concomitant medications was higher (18.3 points) than the MRCI of antiretroviral therapy (5.1 points), 66.7% of the studied population was classified as adherent. Finally, 70% of the patients present some PIP according to the STOPP or LESS-CHRON criteria. The polypharmacy was significantly associated (p = 0.008) with meeting deprescription criteria. CONCLUSION: The elderly people living with HIV present numerous comorbidities and met the criteria for polypharmacy. Their pharmacotherapy complexity is mainly determined by the concomitant treatments. There is a high prevalence of meeting deprescription criteria in people living with HIV over the age of 65 and a clear relationship between polypharmacy and deprescription. The optimization of pharmacotherapy is necessary in this population.

Effectiveness and safety of obeticholic acid in a Southern European multicentre cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid.

BACKGROUND: Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials. AIM: To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy. METHODS: Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI). RESULTS: One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus). CONCLUSIONS: This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability.

Beneficial Effect of Systemic Allogeneic Adipose Derived Mesenchymal Cells on the Clinical, Inflammatory and Immunologic Status of a Patient With Recessive Dystrophic Epidermolysis Bullosa: A Case Report.

Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable inherited mucocutaneous fragility disorder characterized by recurrent blisters, erosions, and wounds. Continuous blistering triggers overlapping cycles of never-ending healing and scarring commonly evolving to chronic systemic inflammation and fibrosis. The systemic treatment with allogeneic mesenchymal cells (MSC) from bone marrow has previously shown benefits in RDEB. MSC from adipose tissue (ADMSC) are easier to isolate. This is the first report on the use of systemic allogeneic ADMSC, correlating the clinical, inflammatory, and immunologic outcomes in RDEB indicating long-lasting benefits. We present the case of an RDEB patient harboring heterozygous biallelic COL7A1 gene mutations and with a diminished expression of C7. The patient presented with long-lasting refractory and painful oral ulcers distressing her quality of life. Histamine receptor antagonists, opioid analgesics, proton-pump inhibitors, and low-dose tricyclic antidepressants barely improved gastric symptoms, pain, and pruritus. Concomitantly, allogeneic ADMSC were provided as three separate intravenous injections of 106 cells/kg every 21 days. ADMSC treatment was well-tolerated. Improvements in wound healing, itch, pain and quality of life were observed, maximally at 6-9 months post-treatment, with the relief of symptoms still noticeable for up to 2 years. Remarkably, significant modifications in PBL participating in both the innate and adaptive responses, alongside regulation of levels of profibrotic factors, MCP-1/CCL2 and TGF-ß, correlated with the health improvement. This treatment might represent an alternative for non-responding patients to conventional management. It seems critical to elucidate the paracrine modulation of the immune system by MSC for their rational use in regenerative/immunoregulatory therapies.

Comparison of next-generation sequencing (NGS) and next-generation flow (NGF) for minimal residual disease (MRD) assessment in multiple myeloma.

Detecting persistent minimal residual disease (MRD) allows the identification of patients with an increased risk of relapse and death. In this study, we have evaluated MRD 3 months after transplantation in 106 myeloma patients using a commercial next-generation sequencing (NGS) strategy (LymphoTrack®), and compared the results with next-generation flow (NGF, EuroFlow). The use of different marrow pulls and the need of concentrating samples for NGS biased the applicability for MRD evaluation and favored NGF. Despite that, correlation between NGS and NGF was high (R2 = 0.905). The 3-year progression-free survival (PFS) rates by NGS and NGF were longer for undetectable vs. positive patients (NGS: 88.7% vs. 56.6%; NGF: 91.4% vs. 50%; p < 0.001 for both comparisons), which resulted in a 3-year overall survival (OS) advantage (NGS: 96.2% vs. 77.3%; NGF: 96.6% vs. 74.9%, p < 0.01 for both comparisons). In the Cox regression model, NGS and NGF negativity had similar results but favoring the latter in PFS (HR: 0.20, 95% CI: 0.09-0.45, p < 0.001) and OS (HR: 0.21, 95% CI: 0.06-0.75, p = 0.02). All these results reinforce the role of MRD detection by different strategies in patient prognosis and highlight the use of MRD as an endpoint for multiple myeloma treatment.