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The potential of combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict disability worsening in multiple sclerosis (MS) remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across thirteen European hospitals, spanned from July 15, 1994, to August 18, 2022, with follow-up until September 26, 2023. We enrolled MS patients who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, median age was 34.2 years (IQR, 27.6-42.4), and 509 patients (70.2%) were female. Median follow-up duration was 6.43 years (IQR, 4.65-9.81). Higher sNfL values associated with an elevated risk of RAW (HR of 1.45; 95% CI 1.19-1.76; P < 0.001), PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003), and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We further examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values (NLGL) exhibited a low risk of all outcomes and served as reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA, and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values (NLGH) showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in MS may identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response.
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BACKGROUND: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. METHODS: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. RESULTS: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. CONCLUSIONS: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.
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Untreated HCV mono and HCV/HIV coinfected women have lower degrees of liver fibrosis (LF) compared to men. Direct acting antiviral (DAA) therapy attains viral eradication in > 90% of patients with progressive LF decline in parallel. Gender-related differences in LF regression in the long term assessed by non-invasive liver fibrosis markers (NILFM) in HCV mono and HCV/HIV coinfected after DAA treatment have not been explored so far. 374 HCV-infected adult patients, 214 of them HCV/HIV coinfected, were followed-up for 24 months after starting DAA therapy. LF was assessed by NILFM: transient elastometry (TE) and several biochemical indexes (APRI, Forns, FIB-4). Men had significantly more advanced LF at baseline than women assessed by NILFM. No LF differences at baseline in age, HIV coinfection course (CD4, HIV viral load), and HCV features (HCV viral load, genotype) were detected. No significant gender differences in LF decline after comparing 24-month and baseline LF values were observed. LF changes after DAA therapy were similar in HCV mono and HCV/HIV coinfected patients and in both sexes. Gender did not influence the course of LF decline after DAA assessed by NILFM: TE (P = 0.8), APRI (P = 0.9), Forns (P = 0.4) and FIB-4 (P = 0.7) by multivariate analysis. No gender differences in the 24 month LF decline after DAA with independence of having HCV mono or HCV/HIV coinfection were found.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Adulto , Masculino , Humanos , Femenino , Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Factores Sexuales , Coinfección/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Hepacivirus/genéticaRESUMEN
INTRODUCTION: Migraine is one of the most common causes of transient visual loss. Optical coherence tomography angiography (OCTA) provides fast and non-invasive imaging of the retinal vessels. We report one case of monocular retinal oligemia demonstrated using OCTA during a migraine attack with aura. CASE DESCRIPTION: A 27-year-old man with a previous history of migraine with visual aura was seen in the emergency room due to acute left hemicranial pain with positive visual symptoms in his right eye. The patient reported a blue stain in his right eye. Optical coherence tomography angiography (OCT-A) showed an extensive area of hypoperfusion in the macular region of his right eye. Forty-eight hours later visual symptoms had improved and the OCT-A showed a significant reduction in the area of hypoperfusion. Seven days later the patient was asymptomatic and retinal perfusion had returned to normal values. CONCLUSION: Monocular involvement suggests that these retinal vascular changes are independent from cerebral vascular changes, supporting the hypothesis of selective retinal ganglion cell layer spreading depression as the possible cause of some cases of retinal migraine.
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Epilepsia , Trastornos Migrañosos , Migraña con Aura , Masculino , Humanos , Adulto , Migraña con Aura/complicaciones , Migraña con Aura/diagnóstico , Tomografía de Coherencia Óptica/métodos , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/diagnóstico , Angiografía , Angiografía con FluoresceínaRESUMEN
Background: Data on coronavirus disease 2019 (COVID-19) incidence in patients with multiple sclerosis (MS) during the first wave have been published but are scarce for the remaining waves. Factors associated with COVID-19 infection of any grade are also poorly known. The aim of this study was to analyze the incidence, clinical features, and risk factors for COVID-19 infection of any grade in patients with MS (pwMS) during waves 1-5. Methods: This study prospectively analyzes the cumulative incidence of COVID-19 from the first to the fifth waves by periodic case ascertainment in pwMS followed at the University Hospital of Getafe (UHG). Global and stratified cumulative incidence was calculated. Logistic regression models were used to estimate the weight of selected variables as risk and prognostic factors. Results: We included 431 pwMS, of whom 86 (20%) were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The overall cumulative incidence of confirmed cases was similar to that of Madrid (13,689 vs. 13,307 per 100,000 habitants) but 3 times higher during the first wave and slightly lower from the second to the fifth waves. The majority (86%) of pwMS developed mild forms of COVID-19. Smoking was the only factor associated with a decreased risk of SARS-CoV2 infection of any grade [odds ratio (OR) 0.491; 95% CI 0.275-0.878; p = 0.017]. Risk factors associated with severe forms were Expanded Disability Severity Scale (EDSS) ≥3.5 (OR 7.569; 95% CI 1.234-46.440) and pulmonary disease (OR 10.763; 95% CI 1.27-91.254). Conclusion: The incidence of COVID-19 was similar in this MS cohort to the general population. Smoking halved the risk of being infected. Higher EDSS and pulmonary comorbidity were associated with an increased risk of severe forms.
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INTRODUCTION: Standard therapy for HIV treatment has consisted of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug regimens (2DR) has been considered for selected patients in part to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase inhibitor (INSTI)-based three-drug regimens (3DR) versus 2DR of dolutegravir (DTG) + rilpivirine (RPV) or DTG + lamivudine (3TC). METHODS: All patients in the Spanish VACH cohort switching to INSTI-based 3DR or a 2DR consisting of DTG + RPV or DTG + 3TC between May 2, 2016 and May 15, 2019 were included. Kaplan-Meier curves and Cox proportional hazard models were used to assess time to/risk of discontinuation due to treatment failure (TF) (defined as virologic failure [VF], immunologic failure, or disease progression) and adverse events (AEs). Three secondary analyses were performed: (1) in restricting the analysis to patients who were virologically suppressed (HIV RNA < 50 copies/mL) at switch; (2) matched analysis (2:1, matched by age, sex, number of previous VFs, and line of regimen), and (3) using VF as the primary endpoint in all patients. RESULTS: Overall, 5047 3DR and 617 2DR patients were analyzed. Baseline characteristics differed between groups; 2DR patients were older, more treatment experienced, and more likely to be virologically suppressed at switch. Time to discontinuation due to TF was significantly shorter for 2DR (P = 0.002). The hazard ratio (HR) for discontinuation due to TF on 2DR vs 3DR was 2.33 (P = 0.003). No difference was observed for time to discontinuation (P = 0.908) or risk of discontinuation due to AEs (HR = 0.80; P = 0.488). Results were qualitatively similar in virologically suppressed patients, matched analysis, and for VF. CONCLUSION: In the real world, the risks of discontinuation due to TF and VF were more than two times higher in patients switching to DTG-based 2DR than INSTI-based 3DR, with no difference in discontinuation due to AEs.
People living with HIV (PLHIV) need lifelong treatment to prevent progression to AIDS. Standard HIV treatments use three different drugs in combination, but these can potentially cause unwanted side effects. Treatments using just two drugs have been developed. These aim to reduce side effects and treat HIV effectively. This study included 5664 participants in Spain who were split into two groups: 5047 participants switched from their old treatment to a three-drug regimen (3DR), and 617 participants switched to a two-drug regimen (2DR). The researchers measured how long it took for the participants to stop taking their treatment because it was not working, or it caused too many side effects. At the end of the study, more than 70% of participants in either group were still taking the same treatment. Of the 30% of participants who stopped treatment because it stopped working, those taking a 2DR stopped sooner than those taking a 3DR. This difference started to appear at about 18 months and got bigger until the study ended, which was 3 years after starting treatment. Participants taking a 2DR were twice as likely to stop treatment because it was not working than those taking a 3DR. There was no difference between the groups for how long it took for participants to stop their treatment because of side effects. These results show that for some PLHIV, the 2DR stopped working sooner than 3DR, without the benefit of fewer side effects.
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Long term liver fibrosis (LF) changes and their best -monitoring non-invasive markers (NILFM) after effective anti-HCV DAA therapy are little- known. Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs) are pivotal in liver inflammation repair. Their plasma levels might assess long-term LF changes after therapy. Overall 374 HCV-infected adult patients, 214 HCV-HIV coinfected, were followed-up for 24 months after starting DAA. LF was assessed by transient elastometry (TE), biochemical indexes (APRI, Forns, FIB-4) and, in 61 individuals, by MMPs and TIMP-1 plasma levels. Several MMPs and TIMP-1 SNPs were genotyped in 319 patients. TE was better than biochemical indexes for early and long-term LF monitoring. MMPs-2,-8,-9 and-TIMP-1 levels and TE displayed parallel declining curves although only TIMP-1 correlated with TE (P = 0.006) and biochemical indexes (P < 0.02). HCV monoinfected had significantly higher baseline NILFM and TIMP-1 plasma values, but lower MMPs levels than coinfected patients. No differences in NILFM course were observed between mono-and coinfected or between different DAA regimens. Only the MMP-2 (-1306 C/T) variant TT genotype associated with higher values of NILFM NILFM decline extends 24 months after therapy. TE and TIMP1 are reliable LF-monitoring tools. NILFM courses were similar in mono-and coinfected patients, DAA regimens type did not influence NILFM course.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Adulto , Antivirales/uso terapéutico , Biomarcadores , Coinfección/complicaciones , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Humanos , Cirrosis Hepática/complicaciones , Metaloproteinasas de la Matriz/genética , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/uso terapéuticoRESUMEN
BACKGROUND: Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF) as it increases the risk of progressive multifocal leukoencephalopathy. A pronounced reduction in absolute lymphocyte counts (ALCs) early after treatment initiation has been suggested to be associated with the occurrence of lymphopenia thereafter. OBJECTIVES: To identify risk factors for DMF-induced lymphopenia and evaluate whether the degree of decrease in the ALCs three months after initiation of DMF treatment is a predictor of the subsequent development of lymphopenia. METHODS: In this real-world Spanish prospective multicenter study conducted in MS patients who started DMF between 2014 and 2019, we analyzed the association between DMF-related lymphopenia and the percentage of early ALCs decline using regression models, considering both, significant lymphopenia (grades 2 + 3) and severe lymphopenia (grade 3). The cutoff values of early ALCs declines were obtained using the ROC curve. RESULTS: Among 532 MS patients treated with DMF, 193 (36.3%) developed any grade of lymphopenia. Older age and lower ALCs at treatment onset predicted the risk for lymphopenia but the best predictive risk factor was the reduction of ALCs within the three first months of treatment. Specifically, a reduction in ALCs≥21.2% was associated with a 6.5-fold higher risk of developing significant lymphopenia, and a decrease in ALCs≥40.2% with a 12.7-fold higher risk of developing severe lymphopenia. CONCLUSIONS: A pronounced reduction in ALCs early after initiation of DMF in MS patients is the best predictive risk factor for the subsequent development of significant lymphopenia.
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Linfopenia , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Dimetilfumarato/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Linfopenia/inducido químicamente , Esclerosis Múltiple/inducido químicamente , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/inducido químicamente , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Estudios Prospectivos , Factores de RiesgoRESUMEN
OBJECTIVES: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. METHODS: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. RESULTS: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). CONCLUSIONS: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Cirrosis Hepática/epidemiología , ARN/uso terapéutico , España/epidemiologíaRESUMEN
Background: Evidence from clinical practice on the effects of switching from emtricitabine/tenofovir disoproxil fumarate (F/TDF) to emtricitabine/tenofovir alafenamide (F/TAF)-based triple-therapy (TT) regimens on renal parameters is limited.Objective: This retrospective analysis evaluated the effects on renal function of switching from F/TDF to F/TAF-based TT regimens with no change in third agent among people living with HIV (PLWH).Methods: Data were from a multicenter Spanish PLWH cohort. Patients with a baseline estimated glomerular filtration rate (eGFR-EPI) measurement, ≥1 follow-up measurement, ≥30 days treatment with F/TAF, and who switched from F/TDF to F/TAF with no change in third agent were included. Multivariate mixed linear models were used to evaluate change from baseline over time in eGFR-EPI. eGFR-EPI changes before and after switch were analyzed in a matched patient subgroup.Results: Overall, 340 patients were included. Mean (95% CI) eGFR-EPI in patients with baseline eGFR-EPI <90 ml/min/1.73m2 (n = 125) was 79.6 (78.0; 81.2) ml/min/1.73m2 at baseline and 81.3 (79.9; 82.7) ml/min/1.73m2 at 12 months after switch. In the patient-matched subgroup (n = 175), median annual eGFR-EPI declined -4.24 ml/min/1.73m2 while on F/TDF and increased +0.93 ml/min/1.73m2 after switch to F/TAF (P < 0.0001). In patients with baseline eGFR-EPI <90 ml/min/1.73m2, median annual eGFR-EPI increased +4.19 mL/min/1.73m2 after switch (P < 0.0001).Conclusion: Switching from F/TDF to F/TAF-based TT regimens while maintaining the same third agent numerically improved eGFR-EPI in PLWH with baseline eGFR-EPI <90 mL/min/1.73m2. eGFR-EPI improved significantly when comparing progression while on F/TDF vs progression after switch, confirming beneficial renal effects of switching to F/TAF in a clinical practice setting.
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Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/uso terapéutico , Estudios de Cohortes , Tasa de Filtración Glomerular , Infecciones por VIH/tratamiento farmacológico , Humanos , Estudios RetrospectivosRESUMEN
BackgroundRecent and reliable estimates on the prevalence of coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in Europe are lacking.AimLeveraged on a study designed to assess HIV/HCV coinfection prevalence, we assessed the prevalence of HIV/HBV coinfection in Spain in 2018 and compared the results with five similar studies performed since 2002.MethodsThis cross-sectional prevalence study was carried out in 43 centres, and patients were selected using simple random sampling. The reference population comprised 40,322 patients and the sample size were 1,690 patients.ResultsThe prevalence of HIV/HBV coinfection in Spain at the end of 2018 was 3.2%. The prevalence in 2002, 2009, 2015, 2016 and 2017 was 4.9%, 3.4%, 3%, 3.9% and 3%, respectively. Among the HIV/HBV-coinfected patients identified in 2018, 16.7% had cirrhosis according to transient elastography and 26.3% tested positive for antibodies against hepatitis D virus. All HIV/HBV-coinfected patients were receiving drugs with activity against HBV, and 97% of those tested for HBV DNA had an HBV DNA load < 80 IU/mL.ConclusionsThe prevalence of HIV/HBV coinfection in Spain remained stable at around 3% for a decade. Our data could facilitate the design of national programmes to control HBV infection and help identify areas of patient management that need improvement.
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Coinfección , Infecciones por VIH , Hepatitis B , Coinfección/epidemiología , Estudios Transversales , Europa (Continente) , Infecciones por VIH/epidemiología , Hepatitis B/epidemiología , Virus de la Hepatitis B , Humanos , Prevalencia , España/epidemiologíaRESUMEN
BACKGROUND: Since 1996, the standard of care (SOC) therapy for HIV treatment has consisted of a backbone of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug combinations (2DC) has been considered for selected patients to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase strand transfer inhibitor (INSTI)-containing triple therapy (TT) to dolutegravir- (DTG) and/or boosted protease inhibitor (bPI)-based 2DC in a large Spanish cohort of HIV patients. METHODS: A retrospective analysis was performed using data from the VACH cohort, a prospective multicentre Spanish cohort of adult HIV patients. All treatment experienced patients initiating a TT of an INSTI combined with two NRTIs or a 2DC-containing DTG and/or a bPI between 01/01/2012 and 01/06/2017 were included. The unit of analysis was patient-regimens. The overall sample analysis was complemented with two sub-analyses. The first sub-analysis focused on patients treated with a backbone plus DTG compared to those treated with DTG+ one other antiretroviral. The second sub-analysis focused on patients with HIV RNA<50 copies/mL at baseline, irrespective of the regimen used. The following endpoints were assessed: time to discontinuation for any reason, time to switch due to virologic failure, and time to switch due to toxicity (reasons for discontinuation according to clinician report in the database). Time-to-event analyses were conducted using Kaplan-Meier survival curves and Cox regression models. RESULTS: Overall 7,481 patients were included in the analysis, contributing to 9,243 patient-regimens. Patient characteristics at baseline differed among groups, with the 2DC group being significantly older and having a higher proportion of women, a longer time on ART and a higher number of previous virologic failures. Median (95% Confidence Interval [C.I.]) time to switch was 2.5 years (2.3, 2.7) in 2DC group versus 2.9 years (2.7, 3.0) in TT. Adjusted hazard ratios (95% C.I.) for discontinuation due to any reason, virologic failure and toxicity in the 2DC vs TT group were 1.29 (1.15; 1.44), 2.06 (1.54; 2.77) and 1.18 (0.94; 1.48), respectively. Results were consistent in the two sub-analyses. CONCLUSION: In this analysis, time to discontinuation and probability of remaining free of virologic failure were significantly higher in patients on INSTI-based TT compared to DTG- and/or bPI-containing 2DC, with no differences in toxicity.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Nivel de Atención/estadística & datos numéricos , Carga Viral , Combinación de Medicamentos , Femenino , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Introducción. La reconstrucción de lesiones del labio superior supone un reto para lograr conservar la función, la competencia labial y la obtención de resultado estético satisfactorio. Se estudian pacientes con lesiones malignas en labio superior y su respectivo tratamiento resectivo y reconstructivo, y se realiza revisión bibliográfica de los principios del abordaje labial y las técnicas reconstructivas con colgajos locales. Material y métodos. Presentación de cuatro casos de pacientes con carcinoma basocelular en labio superior, en quienes se realiza resección con margen de seguridad y técnicas de reconstrucción en "V", en forma pentagonal, avance en VY, colgajo digital nasogeniano y colgajo de avance de mejilla según el defecto obtenido tras la escisión de la lesión cutánea maligna. Resultados. Adecuada coloración y vitalidad de los colgajos, conservación de competencia labial y función de apertura y cierre bucal, cicatrices emplazadas en pliegues naturales. Discusión. Evaluación de opciones reconstructivas para defectos de labio superior según bibliografía. Conclusión. La reconstrucción de labio mediante las técnicas expuestas constituyen excelentes opciones para el tratamiento de defectos de hasta un tercio de longitud del labio superior, ya que conservan la competencia labial y proveen un resultado estético satisfactorio.
Introduction. The reconstruction of defects of the upper lip is a challenge in order to preserve function, lip competence and obtain a satisfactory aesthetic result. Patients with malignant lesions in the upper lip and their respective resective and reconstructive treatment were studied, and a bibliographic review of the principles of the labial approach and reconstructive techniques with local flaps was carried out. Material and methods. Presentation of four cases of patients with basal cell carcinoma of the upper lip, in whom resection is performed with a safety margin and reconstruction techniques in a "V" shape, in a pentagonal shape, VY advancement flap, nasogenian digital flap and cheek advancement flap. Results. Adequate color and vitality of the flaps, preservation of lip competence and function of mouth, scars located in natural folds. Discussion. Evaluation of reconstructive options for upper lip defects according to bibliography. Conclusion. Lip reconstruction using the exposed techniques are excellent options for the treatment of defects of the upper lip, since they preserve lip competence and provide a satisfactory aesthetic result
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Humanos , Masculino , Femenino , Anciano de 80 o más Años , Colgajos Quirúrgicos/inervación , Colgajos Quirúrgicos/trasplante , Neoplasias de los Labios/cirugía , Procedimientos de Cirugía Plástica/métodos , Neoplasias/terapiaRESUMEN
BACKGROUND: Potential increase of cancer incidence is one of the main safety concerns of the disease-modifying therapies employed in Multiple Sclerosis (MS). OBJECTIVE: Detailed description of patients who developed cancer among a prospective cohort of Spanish MS patients on dimethyl fumarate (DMF) treatment. METHODS: We describe patients who developed cancer among a cohort of 886 MS patients on DMF treatment (2681 patient-years), with a median time of exposure of 39.5 months (IQR 23-51.5), who participated in a multicentre and prospective real-world study conducted in 16 Spanish National Health System hospitals from February 2014 to May 2019. Local researchers were periodically contacted by the investigation team to monitor safety issues. Cancer histories were collected from the medical records and the information was updated at July 30th 2020. RESULTS: Eight Caucasian women developed cancer, which accounts for 0.9% and an accumulated malignancy rate of 298.39 cases per 100,000 patient-years of DMF exposure. At the time of cancer diagnosis, age was between 33 to 67 years and median time on DMF treatment 16.5 months (range 1-53). Two patients had familiar history of cancer. No specific cancer lines were found (breast cancer in 2 cases, thyroid in 3, urothelial carcinoma, cervix and a progression to leiomyosarcoma from a mitotically active leiomyoma). DMF was withdrawn during cancer treatment in 6 patients and reintroduced later. All cancers except one are in complete remission. The patient with leiomyosarcoma died by cancer progression. CONCLUSION: A relationship between cancers and DMF is unlikely because the malignancy rate was similar to that of the age-and sex-matched general population, and because of the absence of specific tumour cell lines. Nevertheless, as with other immunosuppressive DMTs, clinicians treating MS should be aware of any potential cancer symptom and demand proper testing.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Neoplasias , Adulto , Anciano , Dimetilfumarato/efectos adversos , Femenino , Humanos , Inmunosupresores/efectos adversos , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Estudios ProspectivosRESUMEN
OBJECTIVES: Sex differences in adult cellulitis, a frequent cause of hospitalization, have not been analyzed. These differences were investigated in a large cellulitis series. METHODS: This was a prospective observational study of 606 Spanish hospitalized cellulitis patients. Different comorbidities, clinical, diagnostic, and treatment data were compared between the sexes. Multiple logistic regression modeling was performed to determine the variables independently associated with sex. RESULTS: Overall 606 adult cellulitis patients were enrolled; 314 (51.8%) were male and 292 (48.2%) were female. Females were older (mean age 68.8 vs 58.9 years, p < 0.0001), less likely to have prior wounds (p = 0.02), and more likely to have venous insufficiency (p = 0.0002) and edema/lymphedema (p = 0.0003) than males. The location of the infection differed between the sexes (p = 0.02). Males were more likely to have positive pus cultures (p = 0.0008), the causing agent identified (p = 0.04), and higher rates of Staphylococcus aureus infection (p = 0.04) and received longer antibiotic treatment (p = 0.03). Factors independently associated with female sex in the multivariate analysis were older age (p < 0.0001), prior cellulitis (p = 0.01), presence of edema/lymphedema as the predisposing factor (p = 0.004), negative versus positive pus culture (p = 0.0002), and location of cellulitis other than in the lower extremities (p = 0.035). CONCLUSIONS: Differences between male and female patients with cellulitis were age, recurrence, presence of edema/lymphedema, positivity of pus culture, and topography of the infection.
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Celulitis (Flemón)/diagnóstico , Celulitis (Flemón)/fisiopatología , Adulto , Anciano , Antibacterianos/uso terapéutico , Celulitis (Flemón)/tratamiento farmacológico , Celulitis (Flemón)/microbiología , Edema , Femenino , Hospitalización , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Caracteres Sexuales , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND: Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited. OBJECTIVE: The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting. METHODS: We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated. RESULTS: Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6-41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy. CONCLUSIONS: Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies.
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Dimetilfumarato/administración & dosificación , Inmunosupresores/administración & dosificación , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/fisiopatología , Estudios Prospectivos , Recurrencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
This study evaluated whether the interval from the first clinic visit until the start of antiretroviral treatment (ART) was correlated with common parameters of immunological recovery among patients with early HIV infection (EHI).We reviewed the medical records of patients with EHI who started ART using integrase strand-transfer inhibitors (ISTIs) within the first 6 months after diagnosis. Simple linear regression analyses were performed to determine whether the interval from the first visit to the start of ART was correlated with 1-year changes in CD4+ cell count, CD8+ cell count, CD4+ percentage, and CD4+/CD8+ ratio.Fifty-three patients with probable or definite EHI started ART using ISTIs between April 2014 and August 2016. Forty-nine patients completed 1 year of follow-up, including 48 men. The routes of HIV transmission were 1 case of needle sharing, 5 cases of heterosexual activity, and 43 cases of men who had sex with men. None of the immunological recovery parameters were correlated with time to the start of ART (CD4+ cell count: Râ=â.12, Pâ=â.42; CD8+ cell count: Râ=â.107, Pâ=â.5; CD4+ percentage: Râ=â.14, Pâ=â.34; CD4+/CD8+ ratio: Râ=â.23, Pâ=â.14). Furthermore, subgroup sensitivity analyses failed to detect significant correlations based on definite or probable diagnoses, treatment using elvitegravir or dolutegravir, or the time from HIV diagnosis to ART initiation.This series of EHI cases indicate that using ART with ISTI-based regimens is efficacious and well-tolerated. However, earlier initiation of treatment was not significantly correlated with common parameters of immunological recovery.
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Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Adulto , Recuento de Linfocito CD4 , Relación CD4-CD8 , Femenino , Infecciones por VIH/inmunología , Humanos , Modelos Lineales , Recuento de Linfocitos , Masculino , Factores de Tiempo , Resultado del TratamientoRESUMEN
Purpose: The presence of the so called disc at risk (a small disc with no cupping) has been considered the main risk factor for the development of non-arteritic anterior ischemic optic neuropathy (NAION). However its role as a prognostic factor has not been studied. Our aim was to determine the weight of disc configuration as a risk and a prognostic factor for NAION. Methods: Case control study. Forty eyes of 40 patients who were diagnosed with NAION between 2008 and 2017, and 120 controls (3 controls for each patient) were included in the study. Disc diameter (DD), cup to disc ratio (CDR), and peripapillar retinal nerve fiber layer thickness (RNFLT) of the non-affected eye were measured using optic coherence tomography (3D OCT 2000, Topcon). Crowding index (CI) was defined as the quotient of average RNFLT and disc area. Mean deviation (MD) at the time of diagnosis and at least three months later was determined using a Humphrey Visual Field Analyzer (SITA standard 24-2 strategy). Visual acuity (VA) was measured using Snellen charts and transformed into LogMAR values. Results: Only CDR was found to be a risk factor for NAION. No correlationship was found between CI and visual loss. Conclusions: DD and CI did not show value as either prognostic or risk factors. Glial tissue may be a part of the content of the optic disc as important as axons. Our results are in line with the latest studies about NAION pathophysiology. Contrary to classic thinking, these papers have not found smaller disc diameters, but smaller values of lamina cribosa depth in NAION patients.
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Disco Óptico/fisiopatología , Neuropatía Óptica Isquémica/fisiopatología , Trastornos de la Visión/fisiopatología , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Pronóstico , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual/fisiología , Pruebas del Campo Visual , Campos Visuales/fisiologíaRESUMEN
BACKGROUND: Cellulitis is a frequent cause of hospital admission of adult patients. Increasing prevalence of multiresistant microorganisms, comorbidities, predisposing factors and medical and surgical therapies might affect cellulitis response and recurrence rate. METHODS: Prospective and observational study of 606 adult patients with cellulitis admitted to several Spanish hospitals. Comorbidities, microbiological, clinical, diagnostic, treatment (surgical and antibiotic) data were analyzed according to the cellulitis response. Good response implied cure. Poor response implied failure to cure or initial cure but relapse within 30 days of hospital discharge. RESULTS: Mean age was 63.3 years and 51.8% were men. Poor responses were significantly associated with age, previous episodes of cellulitis, prior wounds and skin lesions, venous insufficiency, lymphedema, immunosuppression and lower limbs involvement. No differences in ESR or CRP blood levels, leukocyte counts, pus or blood cultures positivity or microbiological or imaging aspects were observed in those with good or poor responses. Regarding antimicrobials, no differences in previous exposition before hospital admission, treatment with single or more than one antibiotic, antibiotic switch, days on antimicrobials or surgical treatment were observed regarding good or poor cellulitis response. Prior episodes of cellulitis (P = 0.0001), venous insufficiency (P = 0.004), immunosuppression (P = 0.03), and development of sepsis (P = 0.05) were associated with poor treatment responses, and non-surgical trauma (P = 0.015) with good responses, in the multivariate analysis. CONCLUSIONS: Prior episodes of cellulitis, non-surgical trauma, venous insufficiency, sepsis and immunosuppression were independently associated with treatment response to cellulitis, but not the causative microorganism, the number of antimicrobials administered or its duration.