Neutralizing antibodies for SARS-CoV-2 infection.

The COVID-19 pandemic has boosted significant research in developing monoclonal antibodies (mAbs) to treat and prevent SARS-CoV-2 infection. Clinical trials have shown that mAbs are safe and effective in preventing hospitalization and death in patients with mild to moderate COVID-19 risk factors for progression. mAbs have also been effective for treating severe disease in seronegative patients and preventing COVID-19. So far, studies have been carried out in a largely unvaccinated population at a time when the omicron variant was not described. Future research should address these limitations and provide information on specific population groups, including immunosuppressed and previously infected individuals.

Efecto de la erradicación del VHC sobre la frecuencia crítica de parpadeo en pacientes coinfectados por VIH/VHC con cirrosis avanzada / Effect of HCV eradication on critical flicker frequency in HIV/HCV coinfected patients with advanced cirrhosis

Antecedentes La frecuencia crítica de parpadeo (FCP), definida como la frecuencia a la que un sujeto percibe una luz parpadeante como continua, se asocia directamente con el nivel de alerta del sistema nervioso central. Métodos Mediante el Hepatonorm analyzer (Medi-Business Freiburg GmGH, Germany) hemos estudiado la FCP en el momento basal y tras la erradicación del virus de la hepatitis C (VHC) en 47 pacientes coinfectados por virus de la inmunodeficiencia humana (VIH)/VHC y cirrosis. Los pacientes tenían una edad media de 52 años; el 81% eran varones y el 80% tenía antecedentes de consumo de drogas. Resultados Observamos un incremento en la FCP al final del tratamiento del VHC comparado con el momento basal (42,3 ± 8,5 Hz vs. 45,9 ± 7,8 Hz; p = 0,001), y una reducción en la proporción de pacientes con encefalopatía hepática subclínica (definida como una FCP < 39 Hz) desde 15 (32%) de los 47 pacientes al inicio a 7 (17%) de los 41 pacientes tras el tratamiento del VHC (p = 0,180). Conclusión La erradicación del VHC en pacientes coinfectados por VIH/VHC aumenta la FCP indicando una mejoría de la función hepática (AU)

Background Critical flicker frequency (CFF), defined as the frequency at which a subject perceives a flickering light as continuous, is directly associated with central nervous system alertness. Methods We studied CFF using the Hepatonorm analyzer (Medi-Business Freiburg GmGH, Germany) at baseline and after hepatitis C virus (HCV) eradication in 47 patients with human immunodeficiency virus (HIV)/HCV coinfection and cirrhosis. Patients had a mean age of 52 years, 81% were male, and 80% had a history of drug use. Results We observed an increase in the CFF at the end of HCV therapy compared to baseline (42.3 ± 8.5 Hz vs. 45.9 ± 7.8 Hz; p = 0.001), and a reduction in the proportion of patients with subclinical hepatic encephalopathy (defined as a CFF <39 Hz) from 15 (32%) of 47 patients at baseline to 7 (17%) of 41 patients after HCV therapy (p = 0.180). Conclusion HCV eradication in HIV/HCV coinfected patients increases CFF, indicating improved liver function (AU)

Effect of HCV eradication on critical flicker frequency in HIV/HCV coinfected patients with advanced cirrhosis.

BACKGROUND: Critical flicker frequency (CFF), defined as the frequency at which a subject perceives a flickering light as continuous, is directly associated with central nervous system alertness. METHODS: We studied CFF using the Hepatonorm analyzer (Medi-Business Freiburg GmGH, Germany) at baseline and after hepatitis C virus (HCV) eradication in 47 patients with human immunodeficiency virus (HIV)/HCV coinfection and cirrhosis. Patients had a mean age of 52 years, 81% were male, and 80% had a history of drug use. RESULTS: We observed an increase in the CFF at the end of HCV therapy compared to baseline (42.3 ±â€¯8.5 Hz vs. 45.9 ±â€¯7.8 Hz; p = 0.001), and a reduction in the proportion of patients with subclinical hepatic encephalopathy (defined as a CFF <39 Hz) from 15 (32%) of 47 patients at baseline to 7 (17%) of 41 patients after HCV therapy (p = 0.180). CONCLUSION: HCV eradication in HIV/HCV coinfected patients increases CFF, indicating improved liver function.

Estrategia de captación para vacunación en una zona de transformacion social / Recruitment strategy for vaccination in a social transformation area

En zona de transformación social del sur de España, se realiza una estrategia de captación para vacunación COVID-19 de personas que cumplen con los requisitos establecidos. Se realiza captación en zona de 360 personas de etnia gitana, mediante un equipo de asistencia social apoyado por Protección Civil. Se reparten mascarillas como reclamo para entablar contacto y dar información del proceso de vacunación. Posteriormente, se procede a la vacunación. Se consiguió vacunar al 40% de la población. Un 14% correspondían a aquellos con enfermedad reciente o vacunados; el resto eran menores. Se recogió, el argumento que tenían para rechazar vacunarse. La organización, y buena integración de los servicios sociales en programas de Salud Pública, ha tenido un importante papel en la creación y aceptación de programas específicos con, resultados evaluables. Tanto la estrategia de captación como la respuesta obtenida se consideraron buenas. Encontramos necesarias este tipo de intervenciones en determinados colectivos.(AU)

In an area of social transformation in southern Spain, a recruitment strategy for COVID-19 vaccination of people who meet the established requirements. A social assistance team, supported by Civil Protection, is recruiting 360 gypsy people in the area. Masks are distributed as a lure to establish contact and provide information on the vaccination process. Subsequently, vaccination is carried out. We managed to vaccinate 40% of the population. Some 14% corresponded to those with recent disease or vaccinated; the rest were minors. The argument they had for refusing to be vaccinated was collected. The organization and good integration of social services in Public Health programs has played an important role in the creation and acceptance of specific programs with evaluable results. Both the recruitment strategy and the response obtained were considered good. We found this type of intervention necessary in certain groups.(AU)

ARAMIS: From systematic errors of NGS long reads to accurate assemblies.

NGS long-reads sequencing technologies (or third generation) such as Pacific BioSciences (PacBio) have revolutionized the sequencing field over the last decade improving multiple genomic applications like de novo genome assemblies. However, their error rate, mostly involving insertions and deletions (indels), is currently an important concern that requires special attention to be solved. Multiple algorithms are available to fix these sequencing errors using short reads (such as Illumina), although they require long processing times and some errors may persist. Here, we present Accurate long-Reads Assembly correction Method for Indel errorS (ARAMIS), the first NGS long-reads indels correction pipeline that combines several correction software in just one step using accurate short reads. As a proof OF concept, six organisms were selected based on their different GC content, size and genome complexity, and their PacBio-assembled genomes were corrected thoroughly by this pipeline. We found that the presence of systematic sequencing errors in long-reads PacBio sequences affecting homopolymeric regions, and that the type of indel error introduced during PacBio sequencing are related to the GC content of the organism. The lack of knowledge of this fact leads to the existence of numerous published studies where such errors have been found and should be resolved since they may contain incorrect biological information. ARAMIS yields better results with less computational resources needed than other correction tools and gives the possibility of detecting the nature of the found indel errors found and its distribution along the genome. The source code of ARAMIS is available at https://github.com/genomics-ngsCBMSO/ARAMIS.git.

Potentially inappropriate medications in older adults living with HIV.

OBJECTIVES: We assessed the prevalence of potentially inappropriate medication (PIM) among older (≥ 65 years) people living with HIV (O-PLWH) in the region of Madrid. METHODS: We analysed the dispensation registry of community and hospital pharmacies from the Madrid Regional Health Service (SERMAS) for the period between 1 January and 30 June 2017, looking specifically at PIMs according to the 2019 Beers criteria. Co-medications were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. RESULTS: A total of 6 636 451 individuals received medications. Of these individuals, 22 945 received antiretrovirals (ARVs), and of these 1292 were O-PLWH. Overall, 1135 (87.8%) O-PLWH were taking at least one co-medication, and polypharmacy (at least five co-medications) was observed in 852 individuals (65.9%). A PIM was identified in 482 (37.3%) O-PLWH. Factors independently associated with PIM were polypharmacy [adjusted odds ratio (aOR) 7.08; 95% confidence interval (CI) 5.16-9.72] and female sex (aOR 1.75; 95% CI 1.30-2.35). The distribution of PIMs according to ATC drug class were nervous system drugs (n = 369; 28.6%), musculoskeletal system drugs (n = 140; 10.8%), gastrointestinal and metabolism drugs (n = 72; 5.6%), cardiovascular drugs (n = 61; 4.7%), respiratory system drugs (n = 13; 1.0%), antineoplastic and immunomodulating drugs (n = 10; 0.8%), and systemic anti-infectives (n = 2; 0.2%). Five drugs accounted for 84.8% of the 482O PLWH with PIMs: lorazepam (38.2%), ibuprofen (18.0%), diazepam (10.2%), metoclopramide (9.9%), and zolpidem (8.5%). CONCLUSIONS: Prescription of PIMs is highly prevalent in O-PLWH. Consistent with data in uninfected elderly people, the most frequently observed PIMs were benzodiazepines and nonsteroidal anti-inflammatory drugs . Targeted interventions are warranted to reduce inappropriate prescribing and polypharmacy in this vulnerable population.

Afasia en paciente con encefalopatía hepática aguda asociada a lesiones corticales cerebrales multifocales / Aphasia in a patient with acute hepatic encephalopathy associated with multifocal cortical brain lesions

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Bacterial translocation and clinical progression of HCV-related cirrhosis in HIV-infected patients.

The aim of the study was to evaluate whether bacterial translocation (BT) predicts the clinical outcome in HIV/HCV-coinfected patients with compensated cirrhosis. A cohort of 282 HIV/HCV-coinfected patients with cirrhosis and no previous liver decompensation (LD) was recruited. Serum levels of the DNA sequences encoding the well-conserved 16S rRNA subunit (16S rDNA), the lipopolysaccharide (LPS) and soluble CD14 (sCD14) at diagnosis of cirrhosis were measured. Primary endpoint was the emergence of the first LD and/or death of any cause. Secondary endpoints were LD, liver-related death (LRD) and death of any cause. After a median (Q1-Q3) follow-up of 51 (27-72) months, 67 patients (24%; 95% CI: 19-29) developed their first LD or died during follow-up. Baseline levels of 16S rDNA, LPS and sCD14 were not associated with the probability of developing the primary endpoint of the study. The mean (SD) survival time free of LD and/or death according to levels of 16S rDNA (<83, 83-196, 197-355, >355 [copies/µL]) was 78 (5), 72 (5), 81 (4) and 82 (4) months, respectively (P = .5). The corresponding figures for LPS (<0.1, 0.1-0.6, 0.6-1.5, > 1.5 [IU/mL]) were 76 (5), 71 (5), 77 (5) and 81 (4) months, respectively (P = .4). Baseline levels of BT serum markers were not associated with any of the secondary endpoints analysed in the study. Thus, BT does not seem to be a relevant predictor of clinical outcome in HIV/HCV-coinfected patients with compensated cirrhosis.

A single mutation in cyclodextrin glycosyltransferase from Paenibacillus barengoltzii changes cyclodextrin and maltooligosaccharides production.

Cyclodextrin glycosyltransferases (CGTases) are bacterial enzymes that catalyze starch conversion into cyclodextrins, which have several biotechnological applications including solubilization of hydrophobic compounds, masking of unpleasant odors and flavors in pharmaceutical preparations, and removal of cholesterol from food. Additionally, CGTases produce maltooligosaccharides, which are linear molecules with potential benefits for human health. Current research efforts are concentrated in the development of engineered enzymes with improved yield and/or particular product specificity. In this work, we analyzed the role of four residues of the CGTase from Paenibacillus barengoltzii as determinants of product specificity. Single mutations were introduced in the CGTase-encoding gene to obtain mutants A137V, A144V, L280A and M329I and the activity of recombinant proteins was evaluated. The residue at position 137 proved to be relevant for CGTase activity. Molecular dynamics studies demonstrated additionally that mutation A137V produces a perturbation in the catalytic site of the CGTase, which correlates with a 10-fold reduction in its catalytic efficiency. Moreover, this mutant showed increased production of maltooligosaccharides with a high degree of polymerization, mostly maltopentaose to maltoheptaose. Our results highlight the role of residue 137 as a determinant of product specificity in this CGTase and may be applied to the rational design of saccharide-producing enzymes.

Effects of CPAP in patients with obstructive apnoea: is the presence of allergic rhinitis relevant?

PURPOSE: The aim of the study is to compare the effects of continuous positive airway pressure (CPAP) on the nasal cavities of patients with obstructive sleep apnoea (OSA) and with or without allergic rhinitis (AR/nonAR). METHODS: This paper is a prospective, longitudinal study. Thirty-four consecutive CPAP treatment-adherent patients with OSA (17 AR and 17 nonAR) were evaluated before and 2 months after treatment, by means of clinical (otorhinolaryngological symptoms, daytime sleepiness, overall and rhinoconjunctivitis-specific quality of life), anatomical (otorhinolaryngological examination), functional (auditory function, tubal function, nasal airflow, and mucociliary clearance), and biological variables (nasal cytology). No humidifier or anti-allergy medicines were used during treatment. RESULTS: Before treatment, patients with AR presented a higher score, compared to nonAR in rhinitis symptoms (4.82 ± 2.53 vs. 0.93 ± 1.02, p = 0.000), otologic symptoms (2.06 ± 1.95 vs. 0.44 ± 0.72, p = 0.004), cutaneous/ocular symptoms (2.12 ± 2.17 vs. 0.65 ± 1.17, p = 0.052), immunoglobulin E (181.82 ± 126.09 vs. 66.13 ± 97.97, p = 0.004), and nasal neutrophils (14.42 ± 31.94 vs. 0.16 ± 0.39, p = 0.031). After treatment, nonAR and AR groups improved in daytime sleepiness (11.53 ± 4.60 vs. 7.53 ± 2.87, p = 0.000 and 13.76 ± 4.93 vs. 7.53 ± 4.41, p = 0.001) respectively and increased nasal neutrophil (0.16 ± 0.39 vs. 5.78 ± 9.43, p = 0.001 and 14.42 ± 31.94 vs. 79.47 ± 202.08, p = 0.035). The symptoms and quality of life improved in patients with AR. NonAR patients, significantly increase nasal dryness (1.65 ± 1.27 vs. 0.00, p = 0.002) and mucociliary clearance times (38.59 ± 24.90 vs. 26.82 ± 23.18, p = 0.016). CONCLUSIONS: CPAP produces inflammation with increased nasal neutrophil levels in AR and nonAR patients. Nevertheless, patients with AR observed an improvement in nasal symptoms and quality of life, whereas in patients without AR, a relevant worsening of nasal dryness and mucociliary transport was observed.

Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

OBJECTIVES: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. METHODS: All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. RESULTS: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/µL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/µL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. CONCLUSIONS: Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control.

Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir- vs. efavirenz-based antiretroviral therapy.

OBJECTIVES: Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). METHODS: A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. RESULTS: After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. CONCLUSIONS: When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.

Luminescent pentafluorophenyl-cycloplatinated complexes: synthesis, characterization, photophysics, cytotoxicity and cellular imaging.

Luminescent mono(pentafluorophenyl) cycloplatinated complexes [Pt(C^N-κC,N)(HC^N-κN)(C6F5)] [HC^N = Hthpy (2-(2-thienyl)pyridine) 2a, Hbt (2-phenylbenzothiazole) 2b, Hpq (2-phenylquinoline) 2c] have been prepared by C­H activation of a HC^N ligand in the corresponding [Pt(HC^N-κN)2(C6F5)2] (1a, 1b, 1c) complexes. Complexes 2 evolve in DMSO solution into solvate complexes and we present here successful routes for the synthesis of [Pt(C^N)(C6F5)(DMSO)] (C^N = thpy 3a, bt 3b). They have been fully characterized (X-ray for 1a, 1c, 2b, 3a and 3b), their electronic absorption and emission properties have been investigated and DFT and TD-DFT calculations for 1a, 1c, 2b and 3a have been carried out. Complexes 3a, 3b and [Pt(ppy)(C6F5)(DMSO)] 4 (Hppy = 2-phenylpyridine) show remarkable stability in a mixed DMSO-cellular medium and their cytotoxicity towards the human lung tumor (A549) and bronchial epithelial non-tumorigenic (NL20) cell lines has been evaluated by MTS assays. Their cellular localization in A549 and NL20 human cells and in mouse embryonic fibroblasts obtained from lungs (LMEFs) has also been investigated by fluorescence microscopy.

Increased risk of non-AIDS-related events in HIV subjects with persistent low CD4 counts despite cART in the CoRIS cohort.

The aim was to analyze clinical complications in HIV-infected subjects who persistently maintain low CD4 levels despite virological response to cART in the Spanish CoRIS cohort. The main inclusion criteria were CD4 counts <200cells/mm(3) at cART-initiation and at least 2years under cART achieving a viral load <500copies/mL. Those patients with CD4 counts <250cells/mm(3) 2years after cART were classified as the Low-CD4 group, and clinical events were collected from this time-point. Poisson regression models were used to calculate incidence rate ratios of death, AIDS-defining events, serious non-AIDS-defining events (NAE) and of each specific NAE category (non-AIDS-defining malignancies (non-ADM), cardiovascular, kidney- and liver-related events). Of 9667 patients in the cohort, a total of 1128 met the criteria and 287 (25.4%) were classified in the Low-CD4 group. A higher risk of death (aIRR: 4.71; 95% CI: 1.88-11.82; p-value=0.001) and of non-ADM were observed in this group (aIRR: 2.23; 95% CI: 1.07-4.63; p=0.03). Our results stress the need to control accelerated aging in this population to counter their increased risk of non-AIDS-defining diseases, particularly cancer, and are consistent with the concept that clinical complications are potentially affected by genetics and lifestyle.

Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients.

Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07-26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.

Switching from zidovudine/lamivudine to tenofovir/emtricitabine improves fat distribution as measured by fat mass ratio.

OBJECTIVES: Fat mass ratio (FMR) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV-infected patients. METHODS: A subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV-1-infected men switching from zidovudine (ZDV)/lamivudine (3TC) to emtricitabine (FTC)/tenofovir (TDF) versus continuing on ZDV/3TC was carried out. FMR was assessed by dual X-ray absorptiometry (DEXA) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted. RESULTS: Sixty-five men were randomized and treated (28 in the FTC/TDF arm and 37 in the ZDV/3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC/TDF arm, adjusted mean FMR decreased by 0.52 at week 72 (P = 0.014), and in the ZDV/3TC arm it increased by 0.13 (P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 (P = 0.003) in the FTC/TDF arm and increased by 0.21 (P = 0.411; P between arms = 0.009) in the ZDV/3TC arm. Baseline FMR and treatment group were significant predictors (P < 0.05) of post-baseline changes in FMR. CONCLUSIONS: Switching from ZDV/3TC to FTC/TDF led to an improvement in FMR, compared with progressive worsening of FMR in subjects receiving ZDV/3TC, showing that fat mass not only increased but was also distributed in a healthier way after the switch.

Amiloidosis leptomeníngea debida a la mutación A25T TTR. A propósito de un caso / Leptomeningeal amyloidosis due to A25T TTR mutation: a case report

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