Efficacy and Safety of Two-Drug Regimens with Dolutegravir plus Rilpivirine or Lamivudine in HIV-1 Virologically Suppressed People Living with HIV.

BACKGROUND: The high effectiveness and safety of the two-drug (2DRs) strategy using dolutegravir (DTG) plus lamivudine (3TC) have led to international guidelines recommending their use for treatment-naive HIV patients. In virologically suppressed patients, de-escalating from 3DRs to DTG plus either rilpivirine (RPV) or 3TC has shown high rates of virological suppression. OBJECTIVES: This study aimed to compare the real-life data of two multicenter Spanish cohorts of PLWHIV treated with DTG plus 3TC (SPADE-3) or RPV (DORIPEX) as a switch strategy, not only in terms of virological suppression, safety, and durability but also in terms of immune restoration. The primary endpoint was the percentage of patients with virological suppression on DTG plus 3TC and DTG plus RPV at weeks 24 and 48. The secondary outcomes included the proportion of patients who experienced the protocol-defined loss of virological control by week 48; changes in immune status in terms of CD4+ and CD8+ T lymphocyte counts and the CD4+/CD8+ ratio; the rate, incidence, and reasons for discontinuation of treatment over the 48-week study period; and safety profiles at weeks 24 and 48. METHODS: We conducted a retrospective, observational, multicenter study of 638 and 943 virologically suppressed HIV-1-infected patients in two cohorts who switched to 2DRs with DTG plus RPV or DTG plus 3TC. RESULTS: The most frequent reasons for starting DTG-based 2DRs were treatment simplification/pill burden or drug decrease. The virological suppression rates were 96.9%, 97.4%, and 99.1% at weeks 24, 48, and 96, respectively. The proportion of patients with virological failure over the 48-week study period was 0.01%. Adverse drug reactions were uncommon. Patients treated with DTG+3TC increased CD4, CD8, and CD4/CD8 parameters at 24 and 48 weeks. CONCLUSIONS: We conclude that DTG-based 2DRs (combined with 3TC or RPV) in clinical practice were effective and safe as a switching strategy, with a low VF and high viral suppression rates. Both regimens were well tolerated, and ADR rates were low, including neurotoxicity and induced treatment discontinuations.

Dolutegravir Plus 3TC in Virologically Suppressed PLWHIV: Immunological Outcomes in a Multicenter Retrospective Cohort in Spain during the COVID-19 Pandemic.

Dolutegravir (DTG) based dual therapies for treating PLWHIV are a standard of care nowadays. Switching to DTG and lamivudine (3TC) safety and efficacy were proven in TANGO randomized clinical trial. This multicenter retrospective study included 1032 HIV virologically suppressed patients switching to DTG+3TC from 13 Spanish hospitals. DTG+3TC provided high rates of undetectable viral load over 96%, corresponding to 96.6% (889/921) at 24 weeks, 97.5% (743/763) at 48 weeks, and 98.3% (417/425) at 96 weeks. No significant differences are evident when comparing the total population according to sex, presence of comorbidity, or presence of AIDS. The analysis for paired data showed an increase in CD4+ cell count. A statistically significant increase in CD4+ lymphocyte count was found in those without comorbidities in the three-time series analyzed [average increase at 24 weeks: 48.7 (SD: 215.3) vs. 25.8 (SD: 215.5), p-value = 0.050; a mean increase at 48 weeks: 75.1 (SD: 232.9) vs. 42.3 (SD: 255.6), p-value = 0.003; a mean increase at 96 weeks: 120.1 (SD: 205.0) vs. 63.8 (SD:275.3), p-value = 0.003]. In conclusion, our cohort demonstrates that DTG+3TC is an effective treatment strategy for virologically-suppressed PLWHIV independent of age, sex, and HIV stage, as well as a safe and durable strategy.

An NMR-Based Model to Investigate the Metabolic Phenoreversion of COVID-19 Patients throughout a Longitudinal Study.

After SARS-CoV-2 infection, the molecular phenoreversion of the immunological response and its associated metabolic dysregulation are required for a full recovery of the patient. This process is patient-dependent due to the manifold possibilities induced by virus severity, its phylogenic evolution and the vaccination status of the population. We have here investigated the natural history of COVID-19 disease at the molecular level, characterizing the metabolic and immunological phenoreversion over time in large cohorts of hospitalized severe patients (n = 886) and non-hospitalized recovered patients that self-reported having passed the disease (n = 513). Non-hospitalized recovered patients do not show any metabolic fingerprint associated with the disease or immune alterations. Acute patients are characterized by the metabolic and lipidomic dysregulation that accompanies the exacerbated immunological response, resulting in a slow recovery time with a maximum probability of around 62 days. As a manifestation of the heterogeneity in the metabolic phenoreversion, age and severity become factors that modulate their normalization time which, in turn, correlates with changes in the atherogenesis-associated chemokine MCP-1. Our results are consistent with a model where the slow metabolic normalization in acute patients results in enhanced atherosclerotic risk, in line with the recent observation of an elevated number of cardiovascular episodes found in post-COVID-19 cohorts.

Dolutegravir plus rilpivirine: benefits beyond viral suppression: DORIPEX retrospective study.

ABSTRACT: Switching dual therapy with dolutegravir (DTG) plus rilpivirine (RPV) was assessed in the SWORD-1 and SWORD-2 studies. Real-life data regarding the immunological impact of this approach on CD4+ and CD8+ T lymphocyte counts and the CD4/CD8 ratio are scarce. We evaluated this strategy on the basis of clinical practice data.A multicentric retrospective cohort study.Treatment-experienced virologically suppressed HIV-1-infected patients who were switched to DTG plus RPV were included. Using different models for paired data, we evaluated the efficacy and immune status in terms of CD4+ and CD8+ T-cell counts and CD4/CD8 ratio at 24 and 48 weeks of treatment.The study population comprised of 524 patients from 34 centers in Spain. Men accounted for 76.9% of patients, with a median age of 53 years. Patients receiving DTG plus RPV reached weeks 24 and 48 in 99.4% and 83.8% of cases, respectively, with only three (0.57%) virological failures. We found a significant decrease in CD8+ T-cell count (log OR -40) at week 24 and an increase in CD4+ T-cell count at week 48 (log OR +22.8). In acquired immunodeficiency syndrome-diagnosed patients, we found a significant increase in the CD4+ T-cell count at week 48 (log OR = 41.7, P = .0038), but no significant changes in the CD8+ T-cell count (log OR = -23.4, P = .54). No differences were found in the CD4/CD8 ratio between the acquired immunodeficiency syndrome subgroup and sex or age.In patients with controlled treatment, dual therapy with DTG plus RPV slightly improved the immune status during the first 48 weeks after switching, not only in terms of CD4+ T-cell count but also in terms of CD8+ T-cell count, with persistently high rates of viral control.

Choroid Plexus Papilloma of the Fourth Ventricle: A Pediatric Patient.

Choroid plexus papilloma is a low-frequency entity in both the adult and pediatric populations. Its clinical presentation is very variable as it depends on its location and length. We must always do the differential diagnosis between papilloma and other intraventricular pathologies. This article is about a case report of a pediatric patient with a Choroid plexus papilloma located in the fourth ventricle, a location that is atypical for the pediatric population.

Recurrent Pituicytoma in a Pediatric Patient: A Case Report

Pituicytoma is a rare tumor that arises from the glial cells of the neurohypophysis. For a long time, it was believed that pituicytomas only appeared in adults. Currently, at least three cases of this entity occurring in children have been reported in the literature. The aim of the present report is to describe the case of a 5-year-old girl who presented to the emergency department with visual disturbances, and the diagnosis was a recurrent pituicytoma. Therefore, the clinical presentation, the radiological features of the tumor, and the corresponding surgical management are described. Additionally, a brief review of the management of this unusual entity was performed.

O pituicitoma é um tumor raro que surge das células gliais da neurohipófise. Durante muito tempo, acreditou-se que os pituicitomas só aparecessem em adultos. Atualmente, pelo menos três casos desta entidade ocorrendo em crianças foram relatados na literatura. O objetivo do presente artigo é descrever o caso de uma menina de 5 anos que chegou à emergência com distúrbios visuais, e o diagnóstico foi um pituicitoma recorrente. A apresentação clínica, as características radiológicas do tumor, e o correspondente manejo cirúrgico foram, portanto, descritos. Além disso, foi realizada uma breve revisão do tratamento desta entidade incomum.

Cerebrospinal Fluids Leaks of the Cranial Vault Management with Compression Cap: Case Series.

Cerebrospinal fluid leaks of the cranial vault, constitute one of the most common complications after neurosurgical procedures. In this paper we introduce to you an observational study, in which a series of patients with this complication where managed by using elastic compression hat during 18 hours per day, for two weeks to four months. Every one of them presented complete resolution of the leak, without any recurrence until actual controls. After that we perform a review of the literature, demonstrating this is a new therapeutic management, being us the first group on reporting it. According to the observed results, it was concluded that despite more studies are required, the use of elastic compression hats for this kind of patients could be effective and safe.

Electrocardiogram classification using reservoir computing with logistic regression.

An adapted state-of-the-art method of processing information known as Reservoir Computing is used to show its utility on the open and time-consuming problem of heartbeat classification. The MIT-BIH arrhythmia database is used following the guidelines of the Association for the Advancement of Medical Instrumentation. Our approach requires a computationally inexpensive preprocessing of the electrocardiographic signal leading to a fast algorithm and approaching a real-time classification solution. Our multiclass classification results indicate an average specificity of 97.75% with an average accuracy of 98.43%. Sensitivity and positive predicted value show an average of 84.83% and 88.75%, respectively, what makes our approach significant for its use in a clinical context.

Glucocorticoids and irreversible damage in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to analyse the relationship between glucocorticoids and damage accrual in SLE. METHODS: We report an observational cohort study including 230 patients with SLE enrolled at diagnosis with 5 years of follow-up. Damage was calculated using the SLICC damage index. Glucocorticoid-related damage was defined as avascular osteonecrosis, osteoporotic fractures, diabetes mellitus or cataracts. Prednisone doses were calculated at the end of the fourth year of follow-up (prednisone-4). A categorical prednisone-4 variable was constructed: no prednisone, ≤7.5 mg/day (low dose), >7.5 mg/day (medium-high dose). The relationship between methylprednisolone pulses and damage was also tested. RESULTS: By the fifth year, 188 patients (82%) had been treated with prednisone. Eighty-seven patients (37.8%) had accrued damage at 5 years. Patients with damage at year 5 had received a higher mean daily prednisone-4 dose (10.4 vs 6 mg/day, P < 0.001). The mean daily prednisone-4 dose was higher in patients accruing glucocorticoid-attributable damage (11 vs 7 mg/day, P = 0.04). Patients taking medium-high doses of prednisone-4 had a higher risk of accruing damage than those taking no prednisone [adjusted odds ratio (OR) 5.39, 95% CI 1.59, 18.27]. Patients taking medium-high doses of prednisone-4 were more likely to develop glucocorticoid-related damage than those on no prednisone (adjusted OR 9.9, 95% CI 1.1, 84). No differences were seen between patients on low doses and those on no prednisone. The cumulative dose of i.v. methylprednisolone-4 was not associated with global or glucocorticoid-related damage. CONCLUSION: Prednisone causes damage in SLE. Doses <7.5 mg/day and methylprednisolone pulses are not associated with damage accrual.

Pain relief in chronic pancreatitis by pancreatico-jejunostomy. An institutional experience

Effective pain control in chronic pancreatitis can be accomplished by pancreatic resection or decompression. Pancreatico-jejunostomy (PJ) has been reported to be effective for relieving pain in 70-80 perecnet, of cases. The present study analyses the authors's long term results with PJ in the treatment of pancreatic pain. From 1963 to 1993, 49 patients with chronic pancreatitis underwent PJ for uncotrollable pain. General and radiologic characteristics, intraoperative findings and outcome were ana-lyzed. Mean age was 35 ñ 13 years, 34 were male and 15 female. Alcoholic etiology was documented in 23 patients. Multiple pancreatic calcifications were found in 33 patients. Pancreatic biopsy confirmed chronica pancreatitis in all patients. There was one operative mortality, 12 minor, and 4 major complications. In a mean follow-up of 6.5 years, 98 perecent of the total group was found to be free of pain. Pancreatic function remained stable in most patients. PJ is an excellent procedure for pain control that allows stable pancreatic function

Case report of primary squamous carcinoma of the rectum

Objetivo. Informar un caso de carcinoma primario epidermoide del recto. Reporte del caso. Se estudió a una mujer de 40 años con hematoquezia y cambios de los hábitos intestinales. La principal alteración de laboratorio fue una anemia leve. El colon por enema y la proctoscopía revelaron una neoplasia rectal a ocho cm del margen anal. La biopsia transendoscópica demostró un carcinoma epidermoide del recto. El ultrasonido transrectal y la TAC de abdomen revelaron una gran masa rectal, con afección transmural, y posible afección de ganglios linfáticos. El antígeno carcinoembrionario estaba elevado (32 ng/mL). La paciente fue sometida a radioterapia con 46 Gy, y 5-fluorouracilo como radiosensibilizador. Tres meses después, una nueva TAC de abdomen demostro reducción significativa del tramaño de la masa, y la paciente se operó realizándose una resección anterior muy baja de recto con técnica de doble engrapadora. El análisis del espécimen demostró un carcinoma epidermoide del tercio medio del recto, invadiendo a través de las muscularis propria, sin afección de ganglios linfáticos, y con bordes proximales, distales y radiales libres de tumor. El antígeno carcinoembrionario postoperatorio regresó a lo normal (1.3 ng/mL). La paciente se encuentra viva y sin evidencia de enfermedad 18 meses después de la operación. Conclusión. El carcinoma epidermoide del recto es una enfermedad rara y la cirugía es una buena opción de tratamiento, con posibilidad de preservación del esfinter dependiendo de la localización del tumor

Simposio: enfermedades del páncreas. Pseudoquistes del páncreas: resultados del tratamiento quirúrgico / Symposium Diseases of pancreas: pseudocysts of pancreas: surgical treatment results

Objetivo: Evaluar los resultados del tratamiento quirúrgico de un grupo de pacientes con pseudoquistes pancreáticos. Sede: Departamentos de cirugía, gastroenterología y endoscopia del Instituto Nacional de la Nutrición "Salvador Zubirán", institución de tercer nivel de atención médica. Diseño: Análisis retrolectivo de una cohorte de pacientes. Pacientes y métodos: Se analizaron los datos demográficos, estudios diagnósticos, hallazgos transoperatorios, tipo de intervención con pseudoquistes pancreáticos que fueron atendidos en el período comprendido entre 1956 y 1994, estableciéndose el último estatus en 1994. Resultados: Hubo predominio de lesiones en pacientes del sexo masculino (63), con edad promedio de 41 años. La frecuencia de pseudoquistes secundarios a un brote de pancreatitis aguda o un episodio de agudización de pancreatitis crónica fue similar. De la misma forma, la etiología alcohólica y biliar como causas de la pancreatitis se presentaron con igual frecuencia. A 47 pacientes se les practicó drenaje externo y al resto drenaje interno o resección. La mortalidad operatoria fue del 7 por ciento. En un periodo promedio de seguimiento de 7 años, se observo desaparición definitiva del pseudoquiste en el 92 por ciento de los pacientes. Conclusiones: De acuerdo a los resultados se propone un esquema terapéutico basado en la relación del pseudoquiste con el conducto pancreático y las condiciones de este último

Endoscopía y laparoscopía en el tratamiento de la colecistitis litiásica asociada a obstrucción beningna de vía biliar / Treatment of gallstones associated to bile duct obstruction using ERCP and laparoscopic cholecystectomy

Objetivo. Analizar la eficacia del tratamiento combinado (endoscopía-laparoscopía) en el manejo de la colecistitis crónica litiástica asociada a obstrucción benigna de la vía biliar. Diseño. Estudio prospectivo. Lugar. Centro de tercer nivel de atención médica. Pacientes. Entre octubre de 1991 y enero de 1994, 270 pacientes con colecistitis crónica litiásica, candidatos a resolución quirúrgica mediante colecistectomía laparoscípica, fueron atendidos en el Instituto Nacional de la Nutrición SalvadorZubirán. En 25 pacientes se prqctico colangiografía retrógrada preoperatoria por sospecha de obstrucción de la vía biliar. Este grupo constituye nuestro grupo de estudio. Resultados. En nueve pacientes (36 por ciento) se corroboró la existencia de colédocolitiasis, extrayéndose exitosamente los litos por esta vía en ocho de ellos. En cinco pacientes más se estableció el diagnóstico de odditis, practicándose papilotomía. En los 11 restantes la vía biliar fue normal. Posteriomente se practicó colecistectomía laparoscópica al grupo de pacientes con vía biliar permeable. Hubo una complicación relacionada con la papilotomía que consistió en perforación duodenal que culminó en defunción. Conclusión. El abordaje combinado (endoscópia/laparoscópica) de la colelitiasis asociada a colédocolitiasis parece ser una alternativa eficiente de manejo