Bullous Pemphigoid Associated With the Use of Sacubitril/Valsartan: A Case Report and Literature Review.

 Bullous pemphigoid (BP) is a complex autoimmune blistering disease with an increased incidence in the comorbid population, particularly among older adults. The occurrence of drug-induced BP is associated with an underlying genetic predisposition, triggering an enhanced immune response, the formation of autoantibodies, and alterations in antigenic properties within the basement membrane zone. With over 90 identified drugs capable of precipitating BP, we present the case of an 87-year-old woman with comorbidities who experienced a medication change from losartan to sacubitril/valsartan. Three months later, erythematous lesions appeared on her lower limbs, progressing to a generalized rash accompanied by itching. Over the following month, these lesions evolved into tense blisters with serous content and intense pain. Suspecting the medication switch to sacubitril/valsartan as the cause, the drug was discontinued, and immunomodulatory treatment was initiated, resulting in a notable improvement in the lesions.

Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with granulomatosis with polyangiitis.

OBJECTIVES: Granulomatosis with polyangiitis (GPA) is a chronic relapsing systemic autoimmune vasculitis. Current treatment of GPA is unsatisfactory, as it relies on strong immunosuppressive regimens, with either CYC or rituximab, which reduce the immunogenicity of several vaccines and are risk factors for a severe form of COVID-19. This emphasizes the need to identify new drug targets and to develop treatment strategies with less harmful side effects. Since CD4+ effector memory T cells (TEM) play a key role in the pathogenesis of GPA, we aimed in this study to modulate CD4+TEM cell activity via Kv1.3 blockade using the specific peptide inhibiter, ShK-186. METHODS: Peripheral blood samples from 27 patients with GPA in remission and 16 age- and sex-matched healthy controls (HCs) were pre-incubated in vitro in the presence or absence of ShK-186, followed by stimulation with phorbol myristate acetate, calcium ionophore and brefeldin-A. The effect of ShK-186 on the cytokine production (IFNγ, TNFα, IL-4, IL-17, IL-21) within total and subsets of CD4+ T helper (CD4+TH) cells were assessed using flow cytometry. RESULTS: ShK-186 reduced the expression level of IFNγ, TNFα, IL-4, IL-17 and IL-21 in CD4+TH cells from patients with GPA in vitro. Further analysis performed on sorted CD4+T cell subsets, revealed that ShK-186 predominantly inhibited the cytokine production of CD4+TEM cells. ShK-186 treatment reduced the production of the pro-inflammatory cytokines to the level seen in CD4+ TH cells from HCs. CONCLUSIONS: Modulation of cellular effector function by ShK-186 may constitute a novel treatment strategy for GPA with high specificity and less harmful side effects.

Prevention and treatment of cisplatin-induced ototoxicity in adults: A systematic review.

OBJECTIVES: Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients. METHODS: Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales. RESULTS: Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions. CONCLUSIONS: Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.

Guselkumab for hidradenitis suppurativa: a phase II, open-label, mode-of-action study.

BACKGROUND: The effectiveness of available biologics for the treatment of hidradenitis suppurativa (HS) is limited. Additional therapeutic options are needed. OBJECTIVES: To investigate the efficacy and mode of action of guselkumab [an anti-interleukin (IL)-23p19 monoclonal antibody] 200 mg subcutaneously every 4 weeks for 16 weeks in patients with HS. METHODS: An open-label, multicentre, phase IIa trial in patients with moderate-to-severe HS was carried out (NCT04061395). The pharmacodynamic response in skin and blood was measured after 16 weeks of treatment. Clinical efficacy was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR), the International Hidradenitis Suppurativa Severity Score System (IHS4), and the abscess and inflammatory nodule (AN) count. The protocol was reviewed and approved by the local institutional review board (METC 2018/694), and the study was conducted in accordance with good clinical practice guidelines and applicable regulatory requirements. RESULTS: Thirteen of 20 patients (65%) achieved HiSCR with a statistically significant decrease in median IHS4 score (from 8.5 to 5.0; P = 0.002) and median AN count (from 6.5 to 4.0; P = 0.002). The overall patient-reported outcomes did not show a similar trend. One serious adverse event, likely to be unrelated to guselkumab treatment, was observed. In lesional skin, transcriptomic analysis revealed the upregulation of various genes associated with inflammation, including immunoglobulins, S100, matrix metalloproteinases, keratin, B-cell and complement genes, which decreased in clinical responders after treatment. Immunohistochemistry revealed a marked decrease in inflammatory markers in clinical responders at week 16. CONCLUSIONS: Sixty-five per cent of patients with moderate-to-severe HS achieved HiSCR after 16 weeks of treatment with guselkumab. We could not demonstrate a consistent correlation between gene and protein expression and clinical responses. The main limitations of this study were the small sample size and absence of a placebo arm. The large placebo-controlled phase IIb NOVA trial for guselkumab in patients with HS reported a lower HiSCR response of 45.0-50.8% in the treatment group and 38.7% in the placebo group. Guselkumab seems only to be of benefit in a subgroup of patients with HS, indicating that the IL-23/T helper 17 axis is not central to the pathophysiology of HS.

Cancer and Non-cancer Fatigue Treated With Bupropion: A Systematic Review.

CONTEXT: Fatigue is a predominant and distressing symptom in cancer and non-cancer conditions for which there is a paucity of recommendations for pharmacological interventions. Bupropion is a novel treatment whose efficacy and safety in the treatment of fatigue are unknown. OBJECTIVES: This study aimed to systematically assess the evidence on the efficacy and safety of bupropion in the treatment of fatigue in people with cancer and non-cancer conditions. METHODS: PubMed, EMBASE, and Ovid Medline databases were searched up to July 26, 2022. Studies were included if they reported bupropion as an intervention for cancer and non-cancer-related fatigue and used an objective scale to assess symptom outcomes. Experimental and quasi-experimental studies in adult patients published in English were included. RESULTS: This review reports on seven studies (three randomized studies, three non-randomized studies, and one case series) that enrolled a total of 584 patients. Bupropion was tested in five studies for treating cancer-related fatigue and in two studies for treating fatigue in non-cancer conditions. The reviewed studies were heterogeneous in relation to the scales used to assess fatigue. Six out of seven studies reported that bupropion significantly reduced the fatigue burden without causing major adverse effects. These positive results must be taken with caution caused by the small sample sizes and low quality of the studies reviewed. CONCLUSION: Bupropion may prove to be an effective and safe intervention for fatigue in cancer and non-cancer conditions. A high-quality randomized trial is warranted to test current preliminary results.

Evaluation of Objective Functions for the Optimal Design of an Assistive Robot.

The number of individuals with upper or lower extremities dysfunction (ULED) has considerably increased in the past few decades, resulting in a high economic burden for their families and society. Individuals with ULEDs require assistive robots to fulfill all their activities of daily living (ADLs). However, a theory for the optimal design of assistive robots that reduces energy consumption while increasing the workspace is unavailable. Thus, this research presents an algorithm for the optimal link length selection of an assistive robot mounted on a wheelchair to minimize the torque demands of each joint while increasing the workspace coverage. For this purpose, this research developed a workspace to satisfy a list of 18 ADLs. Then, three torque indices from the literature were considered as performance measures to minimize; the three torque measures are the quadratic average torque (QAT), the weighted root square mean (WRMS), and the absolute sum of torques (AST). The proposed algorithm evaluates any of the three torque measures within the workspace, given the robot dimensions. This proposed algorithm acts as an objective function, which is optimized using a genetic algorithm for each torque measure. The results show that all tree torque measures are suitable criteria for assistance robot optimization. However, each torque measures yield different optimal results; in the case of the QAT optimization, it produces the least workspace with the minimum overall torques of all the joints. Contrarily, the WRMS and AST optimization yield similar results generating the maximum workspace coverage but with a greater overall torque of all joints. Thus, the selection between the three methods depends on the designer's criteria. Based on the results, the presented methodology is a reliable tool for the optimal dimensioning of assistive robots.

Modifications in self-care, quality of life and therapeutic adherence in patients with rheumatoid arthritis during the SARS-CoV-2 pandemic treated by telehealth

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, causing pain and stiffness in the joints. SARS-CoV-2 increases the clinical vulnerability of the population with RA and has led to the implementation and/or development of telemedicine. Objective: To describe changes in level of therapeutic adherence, quality of life and capacity for self-care agency, during the follow-up period of a group of patients linked to a non-face-to-face multidisciplinary consultation model during the SARS-CoV-2 pandemic. Methodology: Descriptive cohort study (July to October 2020). Description of the level of therapeutic adherence (Morisky Green Test), quality of life (EuroQOL-5-Dimensions-3-Level-version) and self-care capacity (ASA-R Scale) in the context of a telehealth model. A univariate and bivariate analysis was performed (Stata Software, Considered p-value <0.05). Results: Of 71 patients treated under the telehealth model, 85.9% were women, the age range was between 33 and 86 years with a median of 63. The most prevalent comorbidity was arterial hypertension (35.2%). Quality of life did not change during follow-up nor did adherence to treatment, apart from in one item [the patients did not stop taking the medication when they were well (p = 0.029)]. In self-care capacity, there were significant improvements in five dimensions (p < 0.05), without significant differences in the global score. Conclusion: Patients with RA evaluated in the context of telehealth in a period of pandemic did not present significant changes in quality of life, adherence to treatment, or capacity for self-care, and remained close to baseline values when they attended a traditional face-to-face assessment.

INTRODUCCIÓN: La artritis reumatoide (AR) es una enfermedad autoinmune caracterizada por una inflamación crónica que produce dolor y rigidez articular. El SARS-CoV-2 aumenta la vulnerabilidad clínica en pacientes con AR, lo que ha conllevado la implementación o el desarrollo de la telesalud. OBJETIVO: Describir los cambios en el nivel de adherencia terapéutica, la calidad de vida y la capacidad de autocuidado durante el periodo de seguimiento, en un grupo de pacientes con AR vinculados con un modelo de consulta multidisciplinar no presencial, en el curso de la pandemia por SARS-CoV-2. METODOLOGÍA: Estudio de cohorte descriptiva (julio a octubre del 2020). Descripción del nivel de adherencia terapéutica (TEST MORISKY GREEN), calidad de vida (EUROQOL-5-DIMENSIONS-3-LEVEL-VERSION) y capacidad de autocuidado (Escala ASA-R) en el contexto de un modelo de telesalud. Se realizó análisis univariado y bivariado (SOFTWARE Stata®, valor de p considerado <0,05). RESULTADOS: De 71 pacientes atendidos en modalidad de telesalud, el 85,9% fueron mujeres, la mediana de la edad fue de 63 (33-86) anos. La comorbilidad más prevalente fue la hipertensión (35,2%). La calidad de vida no tuvo cambios durante el seguimiento, al igual que la adherencia al tratamiento, excepto en uno de los ítems (los pacientes no dejaron de tomar la medicación cuando se encontraban bien; p = 0,029). En la capacidad de autocuidado hubo mejoras significativas en 5 dimensiones (p < 0,05), sin diferencias significativas en el puntaje global. CONCLUSIÓN: Los pacientes con AR evaluados en el contexto de la telesalud, en un periodo de pandemia, no presentaron cambios significativos en la calidad de vida, la adherencia al tratamiento y la capacidad de autocuidado; se mantuvieron en niveles similares a los valores basales cuando asistían a valoración tradicional presencial.

The biological basis of disease recurrence in psoriasis: a historical perspective and current models.

A key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological 'memory' that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4+ phenotype and forming a local memory. Increasing knowledge of the interleukin (IL)-23/T helper 17 (Th17) cell pathway in psoriasis immunopathology is pointing away from the historical classification of psoriasis as primarily a Th1-type disease. Research undertaken from the 1990s to the mid-2000s provided evidence for the existence of a large population of CD8+ and CD4+ tissue-resident memory T cells in resolved skin, which can initiate and perpetuate immune responses of psoriasis in the absence of T-cell recruitment from the blood. Dendritic cells (DCs) are antigen-presenting cells that contribute to psoriasis pathology via the secretion of IL-23, the upstream regulator of Th17 cells, while plasmacytoid DCs are involved via IL-36 signalling and type I interferon activation. Overall, the evidence discussed in this review indicates that IL-23-driven/IL-17-producing T cells play a critical role in psoriasis pathology and recurrence, making these cytokines logical therapeutic targets. The review also explains the clinical efficacy of IL-17 and IL-23 receptor blockers in the treatment of psoriasis.

Prevalence of hospital readmissions and related factors in patients with autoimmune diseases.

OBJECTIVE: Autoimmune diseases generate an impact on the morbidity and mortality of patients and are a burden for the health system through hospital admissions and readmissions. The prevalence of readmission of patients with these diseases has not yet been described as a group, but rather as sub-phenotype. The objective of this study is to determine the prevalence of hospital readmissions in a Colombian population with autoimmunity and the factors related to readmission. METHODS: All patients with autoimmune diseases who were evaluated by the rheumatology service and hospitalized between August 2018 and December 2019 at the Fundación Hospital Infantil Universitario De San José de Bogotá were described. A bivariate analysis was done, and three multivariate logistic regression models were built with the dependent variable being readmission. RESULTS: Of the total 199 admissions, 131 patients were evaluated and 32% were readmitted. The most frequent sub-phenotype in both groups (readmission and no readmission) was SLE (51% and 59%). The most frequent cause of hospitalization and readmission was disease activity (68.7% and 64.3%). History of hypertension was associated with readmission (adjusted OR: 2.98-95% CI: 1.15-7.72). In a second model adjusted for confounding variables, no factor was associated. In a third model analyzing the history of kidney disease and previous use of immunosuppressants (adjusted for confounding variables), the previous use of immunosuppressants was related to readmission (OR: 2.78-95% CI 1.12-6.89). CONCLUSION: Up to a third of patients with autoimmunity were readmitted and arterial hypertension was an associated factor. This suggested a greater systemic compromise and accumulated damage in patients who have these two conditions that may favor readmission. A history of immunosuppressant use may play a role in readmission, possibly by increasing the risk of developing infections.

IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE).

BACKGROUND: Guselkumab is an interleukin (IL)-23 pathway blocker with proven efficacy in patients with moderate-to-severe plaque psoriasis. Early intervention with guselkumab may result in changes to the clinical disease course versus later intervention. METHODS AND ANALYSIS: Here we present the rationale and design of a phase 3b, randomised, double-blind, multicentre study (GUIDE), comparing treatment effects of guselkumab in patients with short (≤2 years) or longer (>2 years) duration of plaque-type psoriasis, measured from first appearance of psoriatic plaques. Participants achieving skin clearance (Psoriasis Area and Severity Index (PASI)=0) by week 20 and maintaining complete clearance at week 28 visit ('super-responders' (SRe)) will be randomised to continue approved maintenance dosing every 8 weeks (q8w) versus an investigational maintenance dosing interval of 16 weeks (q16w) until week 68. Primary endpoint: proportion of participants in the q8w vs q16w arms with absolute PASI <3 at week 68. Participants with PASI <3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks. Participants not achieving SRe criteria (non-SRe) will remain in the study with q8w guselkumab dosing through week 68. Additional to serum samples obtained from all patients, skin biopsies and whole-blood samples will be taken from SRe and non-SRe participants at various time points in optional substudies. Analyses include: genetics; immunophenotyping (fluorescence-activated cell sorting); gene and protein expression profiling; immunohistology. By merging clinical endpoints with mechanistic findings, this study aims to elucidate how IL-23 blockade with guselkumab can modify the disease course by altering molecular and cellular drivers that cause relapse after treatment withdrawal, particularly among SRe. ETHICS AND DISSEMINATION: Approval obtained from ethics committee Medical Council Hamburg, Germany (PVN5925). GUIDE is compliant with the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: Registered at ClinicalTrials.gov (NCT03818035). All primary endpoint results (prespecified analyses) will be submitted to peer-reviewed, international journals within 18 months after primary completion date.

Palmo-plantar hyperkeratosis associated with HTLV-1 infection: a case report.

BACKGROUND: Palmoplantar hyperkeratosis is a cutaneous manifestation that had not been clearly associated with infection by the human T-cell lymphotropic virus, which is a retrovirus that in most cases does not develop clinical pathologies and its symptoms may be undetected. The skin is one of the most affected organs, however until now only seborrheic dermatitis, xerosis/ichthyosis and infective dermatitis associated with HTLV-1 have been described as cutaneous clinical manifestations of this disease. CASE PRESENTATION: We present the case of a 36-year-old male patient with serologically documented HTLV-1 infection, who presented symptoms of diarrhea, malabsorption due to Strongyloides stercoralis, and in whom a physical examination revealed an association with generalized xerosis and palmoplantar keratoderma confirmed by skin biopsy. Other infectious etiologies and malignancy were ruled out. This clinical manifestation was managed with dermal hydration, and skin care which improved the thickened skin and make it less noticeable. CONCLUSIONS: According to our experience, this is the first reported case of palmoplantar keratoderma associated with a human lymphotropic virus infection. This is a skin manifestation that has not been confirmed in conjunction with HTLV-I before. This implies that palmoplantar keratoderma is a new clinical manifestation of this infection, that should be considered in the initial approach of patients in endemic areas with these dermatological characteristics.

C3 Glomerulopathy, a pathology with scarce evidence. A case report.

C3 Glomerulonephritis (C3GN) is a rare disease with an estimated incidence of 1-2 cases per million, caused by an alteration in the alternative complement pathway, although its complete physiopathology remains uncertain. Treatment evidence is poor. Immunosuppressive therapy can be initiated in more severe cases. Progression rates to end stage kidney disease are of up to 50% within a decade, and the posttransplant recurrence rates of 45-60%. We describe the case of a young man without any past medical history, with lower extremities edema, dyspnea, and kidney function deterioration. The patient was ultimately diagnosed with C3GN.

Is there any relationship between massive ascites and elevated CA-125 in systemic lupus erythematosus? Case report and review of the literature.

Systemic lupus erythematosus (SLE) is a chronic, multisystemic autoimmune disease of variable presentation. Massive ascites in the context of SLE is infrequent. Even so, it has been reported that ascites may be the first manifestation of SLE. It is difficult to diagnose due to the multiple possible aetiological causes of ascites. There is a rare entity called Pseudo-Pseudo Meigs Syndrome (PPMS) in patients with SLE who have ascites, pleural effusion, and CA-125 elevation unrelated to malignancy. We present two cases of massive ascites, pleural effusion and elevation of CA-125 with a history of SLE diagnosis. One of these cases was diagnosed with PPMS and another associated with neoplasm of ovarian origin.

Tercer caso de vasculitis leucocitoclástica cutánea secundaria al uso de oxacilina: reporte de caso / Third case in the literature of cutaneous leukocytoclastic vasculitis secondary to oxacilin use

Resumen La vasculitis leucocitoclastica es una patologìa que compromete los vasos pequeños y cuya causa predominantemente se ha descrito como idiopatica. Se presenta el caso de una mujer de 78 años hipertensa, diabética y con enfermedad renal crónica en estadio 5, que presentó lesiones limitadas a la piel posterior a la administración de oxacilina para manejo de bacteremia por SAMS. La presentación clínica se basó en purpuras palpables predominantemente en miembros inferiores y lesiones dolorosas coalescentes que formaban ampollas de contenido hemorrágico. Estas lesiones resolvieron gradualmente después del cambio de la terapia mencionada anteriormente. La biopsia fue compatible con vasculitis leucocitoclástica, con paraclínicos que descartaron causas infecciosas y autoinmunes.

Abstract Leukocytoclastic vasculitis is a pathology that involves small vessels and whose cause has been predominantly described as idiopathic. The clinical case of a 78-year-old woman with hypertension, diabetic and chronic stage 5 kidney disease, who presented limited skin lesions after administration of oxacillin for management of bacteremia by MSSA. The clinical presentation consisted on palpable purpura predominantly in the lower limbs and painful coalescent lesions that formed blisters of hemorrhagic content. Lesions gradually resolved after the change of the therapy mentioned above. The biopsy was compatible with leukocytocastic vasculitis, with paraclinics who ruled out infectious and autoimmune causes.

Criptococosis y linfocitopenia T CD4 idiopática: Reporte de un caso / Cryptococcosis and idiopathic CD4 T lymphocytopenia: A case report

Resumen La linfocitopenia T CD4 idiopática (LCI) es un síndrome clínico inusual que se caracteriza por un déficit de células T CD4+ circulantes en ausencia de infección por VIH u otra condición de inmunosupresión. Los pacientes con dicha enfermedad pueden presentarse asintomáticos o con infecciones oportunistas, las más frecuentes son por criptococo, micobacterias o virales como herpes zoster. Presentamos el caso de un hombre de 32 años, sin antecedentes, en quien se descartó infección por retrovirus, con recuento de linfocitos T CD4+ menor a 300 células/m3; se diagnosticó LCI posterior al diagnóstico de criptococomas cerebrales mediante hallazgos imagenológicos los cuales fueron congruentes con estudios microbiológicos.

Summary Idiopathic CD4 T lymphocytopenia (ICL) is an unusual clinical syndrome characterized by a deficit of circulating CD4 + T cells in the absence of HIV infection or another immunosuppression condition. Patients with this disease may present asymptomatic or with opportunistic infections, the most frequent are cryptococcus, mycobacteria or viral such as herpes zoster. We present a case of a 32-year-old man with no prior disease, in whom retrovirus infection was discarded, with CD4 + T lymphocyte count less than 300 cells/m3; ICL was diagnosed after the diagnosis of brain cryptococomas by imaging findings which were consistent with microbiological studies.

Clinical questionnaires for chronic obstructive pulmonary disease diagnosis: A systematic review and meta-analysis / Cuestionarios clínicos para el diagnóstico de la enfermedad pulmonar obstructiva crónica. Revisión sistemática y metaanálisis

Abstract Introduction: The use of early screening questionnaires for chronic obstructive pulmonary disease (COPD) in primary health care could improve underdiagnosis. Several instruments are currently available, but there is scant information on their diagnostic performance. Objective: To determine the validity of different questionnaires for COPD diagnosis. Materials and methods: A systematic review and a meta-analysis of diagnostic test accuracy were carried out. A search of the literature published between July 1, 1997, and June 30, 2019 was performed in PubMed, EMBASE, and LILACS databases using MeSH and DeCS terms and the PICO strategy. Based on the inclusion and exclusion criteria, two reviewers selected the articles for complete analysis. Article quality was assessed using the QUADAS instrument. Results: 19 articles were included for analysis. Overall results were: sensitivity: 68.1% (95%CI: 66.7% -69.4%); specificity: 64.9% (95%CI: 64.3-65.5); positive likelihood ratio: 2.024 (95%CI: 1.7152.388); negative likelihood ratio: 0.407 (95%CI: 0.289-0.573); and receiver operating characteristic area under the curve (ROC AUC): 0.75. The COPD-PS questionnaire reported the highest performance with sensitivity of 0.673 (95%CI: 0.653-0.692), specificity of 0.663 (95%CI: 0.65.5- 0.651), and ROC AUC of 0.750. It was followed by LFQ with sensitivity of 0.840 (95%CI: 0.806-0.871), specificity of 0.312 (95%CI: 0.289-0.336), and ROC AUC of 0.730. Finally, CDQ had sensitivity of 0.798 (95%CI: 0.764-0.829), specificity of 0.517 (95%CI: 0.495-0.538), and ROC AUC of 0.727. Conclusion: Clinical prediction instruments for COPD diagnosis have an acceptable performance. The COPD-PS, LFQ and CDQ questionnaires show a similar performance.

Resumen Introducción. El uso de cuestionarios de predicción clínica para el diagnóstico de la enfermedad pulmonar obstructiva crónica (EPOC) en atención primaria en salud podría mejorar el subdiagnóstico de esta enfermedad. Hoy en día existen varios instrumentos de este tipo; sin embargo, hay poca información sobre su rendimiento diagnóstico. Objetivo. Determinar la validez del uso de los diferentes cuestionarios de predicción clínica para el diagnóstico de la EPOC. Materiales y métodos. Se realizó una revisión sistemática con metaanálisis de prueba diagnóstica en las bases de datos PubMed, EMBASE y LILACS a partir de la estrategia PICO y utilizando términos MeSH y DeCS. Se incluyeron los estudios publicados entre julio 1 de 1997 y junio 30 de 2019. Dos revisores seleccionaron los artículos para análisis completo con base en los criterios de inclusión y exclusión. La calidad de los artículos se evaluó con el instrumento QUADAS. Resultados. Se incluyeron 19 artículos para el análisis. En cuanto a la evaluación global de los cuestionarios se obtuvieron los siguientes datos: sensibilidad: 68.1% (IC95%: 66.7-69.4); especificidad: 64.9% (IC95%: 64.3-65.5); razón de verosimilitud positiva: 2.024 (IC95%: 1.715-2.388); razón de verosimilitud negativa: 0.407 (IC95%: 0.289-0.573) y el área bajo la curva de características del receptor (ACOR): 0.75. El cuestionario COPD-PS reportó el mayor rendimiento -sensibilidad: 0.673 (IC95%: 0.653-0.692), especificidad: 0.663 (IC95%: 0.655-0.671) y ACOR: 0.750-; seguido de LFQ -sensibilidad: 0.840 (IC95%: 0.806-0.871), especificidad: 0.312 (IC95%: 0.289-0.336) y ACOR: 0,730-, y CDQ -sensibilidad: 0.798 (IC95%: 0.764-0.829), especificidad: 0.517 (IC95%: 0.495-0.538) y ACOR: 0.727-. Conclusión. Los instrumentos de predicción clínica para el diagnóstico de EPOC tienen un rendimiento aceptable, pues los valores de sensibilidad obtenidos a través de estos son superiores a los de la evaluación individual de la sintomatología respiratoria que se puede hacer a través de la historia clínica habitual.

Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab.

Cellular sources of IL-23 and IL-17A driving skin inflammation in psoriasis remain unclear. Using high-dimensional unsupervised flow cytometry analysis, mononuclear phagocytes and T cells were examined in the same lesions of patients before and during guselkumab (IL-23p19 blocker) or secukinumab (IL-17A blocker) treatment. Among CD11c+HLA-DR+ mononuclear phagocytes, CD64brightCD163-CD14brightCD1c-CD1a‒ inflammatory monocyte‒like cells were the predominant IL-23-producing cells and, together with CD64-CD163-CD14-IL-23p19-TNF-α+ inflammatory dendritic cell‒like cells, were increased in lesional compared with those in nonlesional skin taken from the same patient. Within T cells, CD8+CD49a+ and/or CD103+ tissue-resident memory T cells, CD4+CD25+FoxP3+ regulatory T cells, and CD4+CD49a-CD103- T cells were increased. Moreover, CD4+CD49a-CD103- T cells and the relatively rare CD8+ memory T cells equally contributed to IL-17A production. Both treatments decreased the frequencies of inflammatory monocyte‒like, inflammatory dendritic cell‒like, and CD4+CD49a-CD103- T cells. In contrast, guselkumab reduced memory T cells while maintaining regulatory T cells and vice versa for secukinumab. Neither drug modified the frequencies of IL-17A+IL‒17F+/- CD4+ or CD8+ T cells. This study reveals the identity of the major IL-23+ mononuclear phagocyte and IL-17+ T-cell subsets in psoriatic skin lesions and paves the way for a better understanding of the mode of action of drugs targeting the IL-23/IL-17A pathway in psoriasis.

Kinematics and Workspace Analysis of xArm6 Robot for Activities of Daily Living.

Recent statistics reveal that the number of individuals with upper or lower extremity dysfunctions has increased alarmingly. It is estimated that approximately 3.3 million Americans use a wheelchair, with an expected 2 million new wheelchair users every year. To assist powered wheelchair users with limited upper limb function, we have been exploring assistive robots that can be mounted on a wheelchair to perform essential activities of daily living (ADL), such as picking/placing an object from out of reach, feeding, etc. In this research, a 6DoF robot, xArm-6 was used as an assistive robot to provide ADL assistance. Experiments were conducted with xArm6 Robot to investigate the motion trajectories and workspace covering essential ADLs. In kinematic analysis, modified Denavit-Hartenberg parameters are used to identify the Robot's motion path and workspace. On the other hand, the iterative Newton-Euler method was used for dynamic analysis to estimate the joint torques corresponding to each ADL. Experimental results show that xArm-6 can be used for some selected ADLs tasks but not for all essential ADLs.