Abstract This review focuses on the pathophysiology of digital vasculopathy in patients with systemic sclerosis and discusses studies published between 2017 and 2023. Several mechanisms of vascular damage that explain the pathophysiology of digital vasculopathy in patients with systemic sclerosis are discussed, such as uncontrolled activation of the immune system that does not allow control of profibrotic changes, predominance of vasoconstriction phenomena over vasodilatation phenomena, modification of vascular cytoarchitecture, ineffective angiogenesis, decrease in the number of endothelial cell progenitors, release of inhibitory molecules of the neurovascular relationship, increase of adhesion molecules that promote fibrosis and the appearance of digital ulcers, and stimulation of a complex process of mesenchymal endothelial transition. These mechanisms could amplify the damage established by increased oxidative stress and autoantibodies. They also point to the complexity of digital vasculopathy in systemic sclerosis and open new possibilities to improve the diagnosis and treatment of these patients.

Resumen Esta revisión se enfoca en la fisiopatología de la vasculopatía digital en pacientes con esclerosis sistémica y en ella se analizan estudios publicados entre los años 2017 y 2023. Se comentan varios mecanismos de daño vascular que explican la fisiopatología de la vasculopatía digital en pacientes con esclerosis sistémica, como la activación no controlada del sistema inmunitario que no permite controlar los cambios profibróticos, predominio de fenómenos de vasoconstricción sobre los de vasodilatación, modificación de la citoarquitectura vascular, angiogénesis ineficaz, disminución de la cantidad de progenitores de células endoteliales, liberación de moléculas inhibitorias de la relación neurovascular, aumento de moléculas de adhesión que promueven la fibrosis y la aparición de úlceras digitales y estimulación de un proceso complejo de transición endotelio-mesénquima. Estos mecanismos pueden amplificar el daño establecido por el creciente estrés oxidativo y los autoanticuerpos, y apuntan a la complejidad de la vasculopatía digital en la esclerosis sistémica; y también permiten abrir nuevas posibilidades para mejorar el diagnóstico y tratamiento de estos pacientes.

Abstract Objective: To review the literature and synthesize evidence on pathophysiological interactions attributed to the simultaneous occurrence of COVID-19 and preeclampsia. Methods: A systematic review was conducted from November (2021) to January (2022) to retrieve observational studies published on the PubMed, LILACS, SciELO Brazil and Google Scholar databases. The search was based on the descriptors [(eclampsia OR preeclampsia) AND (COVID-19)]. Quantitative studies that pointed to pathophysiological interactions were included. Literature reviews, studies with HIV participants, or with clinical approach only were excluded. The selection of studies was standardized and the evaluation was performed by pairs of researchers. Results: In this review, 155 publications were retrieved; 16 met the inclusion criteria. In summary, the physiological expression of angiotensin-converting enzyme-2 (ACE-2) receptors is physiologically increased in pregnant women, especially at the placental site. Studies suggest that the coronavirus binds to ACE-2 to enter the human cell, causing deregulation of the renin-angiotensin-aldosterone system and in the ratio between angiotensin-II and angiotensin-1-7, inducing manifestations suggestive of preeclampsia. Furthermore, the cytokine storm leads to endothelial dysfunction, vasculopathy and thrombus formation, also present in preeclampsia. Conclusion: The studies retrieved in this review suggest that there is a possible overlap of pathophysiological interactions between COVID-19 and preeclampsia, which mainly involve ACE-2 and endothelial dysfunction. Given that preeclampsia courses with progressive clinical and laboratory alterations, a highly quality prenatal care may be able to detect specific clinical and laboratory parameters to differentiate a true preeclampsia superimposed by covid-19, as well as cases with hypertensive manifestations resulting from viral infection. Objective COVID19 COVID 19 COVID-1 Methods 2021 (2021 2022 (2022 PubMed LILACS databases eclampsia COVID19. . (COVID-19)] included reviews participants excluded researchers Results 15 1 criteria summary angiotensinconverting angiotensin converting enzyme2 enzyme 2 enzyme- ACE2 ACE (ACE-2 women site ACE- cell reninangiotensinaldosterone renin aldosterone angiotensinII II angiotensin17, angiotensin17 7, 7 angiotensin-1-7 Furthermore dysfunction formation Conclusion alterations covid19, covid19 covid 19, covid-19 infection COVID1 COVID- 202 (202 (COVID-19) (ACE- angiotensin1 angiotensin-1- covid1 covid-1 20 (20 (COVID-19 (ACE angiotensin-1 covid- (2 (COVID-1 angiotensin- ( (COVID- (COVID

Resumo Objetivo: Revisar a literatura e sintetizar evidências sobre interações fisiopatológicas atribuídas à ocorrência simultânea de COVID-19 e pré-eclâmpsia. Métodos: Uma revisão sistemática foi conduzida entre novembro (2021) a janeiro (2022) para recuperar estudos observacionais publicados no PubMed, LILACS, SciELO Brasil e Google scholar. A busca foi baseada nos descritores [(eclâmpsia OR pré-eclâmpsia) AND (COVID-19)]. Estudos quantitativos que apontaram interações fisiopatológicas foram incluídos. Estudos de revisão, com participante HIV e apenas com enfoque clínico foram excluídos. A seleção dos estudos foi padronizada com avaliação por duplas de pesquisadores. Resultados: Nesta revisão, 155 publicações foram recuperadas; 16 preencheram os critérios de inclusão. Em síntese, a expressão fisiológica de receptores da enzima conversora da angiotensina-2 (ECA-2) é fisiologicamente potencializada em gestantes, especialmente no sítio placentário. Os estudos sugerem que o coronavírus se liga à ECA-2 para entrar na célula humana, ocasionando desregulação do sistema renina-angiotensina-aldosterona e da razão entre angiotensina-II e angiotensina-1-7, induzindo manifestações sugestivas de pré-eclâmpsia. Ademais, a tempestade de citocinas conduz à disfunção endotelial, vasculopatia e formação de trombos, também presentes na pré-eclâmpsia. Conclusão: Os estudos recuperados nesta revisão sugerem que a superposição de alterações fisiopatológicas entre a COVID-19 e a pré-eclâmpsia envolve, principalmente, a ECA-2 e disfunção endotelial. Tendo em vista que a pré-eclâmpsia cursa com alterações clínicas e laboratoriais progressivas, a atenção pré-natal de qualidade pode ser capaz de detectar parâmetros clínicos e laboratoriais importantes para diferenciar a pré-eclâmpsia verdadeira sobreposta por COVID-19, bem como os casos que mimetizam a doença hipertensiva consequente à infecção viral. Objetivo COVID19 COVID 19 COVID-1 préeclâmpsia. préeclâmpsia pré eclâmpsia. eclâmpsia Métodos 2021 (2021 2022 (2022 PubMed LILACS scholar COVID19. . (COVID-19)] incluídos excluídos pesquisadores Resultados 15 recuperadas 1 inclusão síntese angiotensina2 angiotensina 2 angiotensina- ECA2 ECA (ECA-2 gestantes placentário ECA- humana reninaangiotensinaaldosterona renina aldosterona angiotensinaII II angiotensina17, angiotensina17 7, 7 angiotensina-1-7 Ademais endotelial trombos Conclusão envolve principalmente progressivas prénatal natal COVID19, 19, viral COVID1 COVID- 202 (202 (COVID-19) (ECA- angiotensina1 angiotensina-1- 20 (20 (COVID-19 (ECA angiotensina-1 (2 (COVID-1 ( (COVID- (COVID

RESUMO Objetivo: Determinar os efeitos da deficiência de vitamina D nos microvasos da retina usando angiotomografia de coerência óptica. Métodos: Este estudo foi planejado para ser do tipo caso-controle observacional. Foram avaliados 98 olhos de pacientes com deficiência de vitamina D e 96 olhos de participantes saudáveis com nível sérico de vitamina D superior a 30 ng/mL. Foram adquiridas imagens de varredura centralizadas na mácula, com um tamanho de 6,00 × 6,00 mm. Mediram-se a densidade dos vasos nos plexos capilares superficial e profundo da retina, a área da zona avascular foveal e a área do fluxo coriocapilar. Resultados: Os grupos mostraram-se semelhantes em relação à melhor acuidade visual corrigida, ao gênero, ao comprimento axial, ao erro refrativo, à idade e à pressão intraocular ajustada. O nível médio de vitamina D foi significativamente menor no grupo de estudo (p=0,021). As densidades total, parafoveal e perifoveal do plexo capilar profundo foram significativamente maiores no grupo de estudo que no grupo controle (respectivamente, p=0,012, p=0,014 e p=0,023). As áreas da zona avascular foveal e do fluxo coriocapilar foram semelhantes nos dois grupos (respectivamente, p=0,37 e p=0,27). Além disso, houve uma forte correlação negativa do nível sérico de vitamina D com as densidades vasculares medidas em toda a imagem e nas regiões parafoveais e perifoveais do plexo capilar profundo no grupo de estudo (respectivamente, ρ de Spearman = −0,71, p=0,043; ρ de Spearman = −0,79, p=0,011; e ρ de Spearman = −0,74, p=0,032). Conclusão: Pode ocorrer um aumento na densidade vascular da retina devido a alterações estruturais dos vasos causadas pela deficiência de vitamina D. O aumento da densidade vascular, especialmente no plexo capilar profundo, pode ser usado para o diagnóstico precoce da vasculopatia associada à deficiência de vitamina D.

ABSTRACT Purpose: To determine the effects of vitamin D deficiency on retinal microvascularity using optical coherence tomography angiography. Methods: This study was designed as an observational case-control study. Ninety-eight eyes of patients with vitamin D deficiency and 96 eyes of healthy participants with serum vitamin D level >30 ng/mL were studied. Macula centered, 6.00 × 6.00 mm scan size images were taken. The vessel densities in the superficial and deep retinal capillary plexus, foveal avascular zone area, and choriocapillaris flow area were measured. Results: The groups were comparable in terms of best-corrected visual acuity, sex, axial length, refractive error, age, and adjusted intraocular pressure. The average vitamin D level was significantly lower in the study group (p=0.021). The whole, parafoveal, and perifoveal vessel densities in the deep capillary plexus were considerably higher in the study group than in the control group (p=0.012, p=0.014, and p=0.023, respectively). The foveal avascular zone area and the choriocapillaris flow area were similar in both groups (p=0.37 and p=0.27, respectively) there was a strong negative correlation between the serum vitamin D level and vessel density in the whole image, parafoveal, and perifoveal regions of the deep capillary plexus in the study group (Spearman’s rho=-0.71, p=0.043; Spearman’s rho= -0.79, p=0.011; and Spearman’s rho = -0.74, p=0.032; respectively). Conclusion: An increase in vessel density might originate from vascular structural changes caused by vitamin D deficiency. The increased vessel density, especially in the deep capillary plexus, can enable early diagnosis of vitamin D-associated vasculopathy.

Resumen La vasculopatía livedoide (VL) es una manifestación cutánea de varias enfermedades que conducen a una trom bosis no inflamatoria de los vasos dérmicos. Se presenta el caso de una mujer de 26 años con antecedente de diagnóstico de vasculopatía livedoide de 4 años y 8 meses, además de una úlcera no cicatrizante de más de un año de evolución. Debido a la respuesta refractaria a la atención estándar, se añadió oxígeno hiperbárico a baja presión (LPHBOT) al esquema terapéutico (azatriopina 2.5 mg/kg, ácido fólico y ácido acetilsalicílico). Después de 12 sesiones de LHBOT (60 min, 1,45 ATA ≈100% O2), las úlceras tuvieron una curación completa con un alivio significativo del dolor y no hubo recurrencia durante 16 meses. Se necesitan más estudios para determinar la eficacia de TOHB para el tratamiento del VL.

Abstract Livedoid vasculopathy (LV) is a cutaneous manifestation of several diseases that lead to non-inflammatory thrombosis of dermal vessels. We report the case of a 26-year-old female with a 4 years and 8 months-old history of diagnosis of LV and a non-healing ulcer of more than a year of evolution. Because of refractory response to standard care, low-pressure hyperbaric oxygen (LPHBOT) was added to the therapeutic scheme (azathiopine 2.5 mg/kg, folic acid and acetylsalicylic acid). After 12 sessions of LHBOT (60 min, 1.45 ATA ≈100% O2), ulcers achieved complete healing with significant pain relief and no recurrence was present over 6 months. More studies are necessary to determine the effectiveness of HBOT for LV treatment.

Resumen La inmunodeficiencia combinada (IDC) por deficiencia de DOCK8 es un error innato de la inmunidad, caracterizado por alteración en linfocitos T y B; el espectro de manifestaciones incluye alergia, autoinmunidad, inflamación, predisposición a cáncer e infecciones recurrentes. La deficiencia de DOCK8 se puede distinguir de otras IDC o dentro del espectro de síndromes de hiper-IgE porque presenta una profunda susceptibilidad a las infecciones virales de la piel, con cánceres de piel asociados y alergias alimentarias graves. El locus subtelomérico 9p24.3, donde se ubica DOCK8, incluye numerosos elementos repetitivos de secuencia que predisponen a la generación de grandes deleciones de la línea germinal, así como a la reparación del ADN somático, mediada por recombinación. La producción residual de la proteína DOCK8 contribuye al fenotipo variable de la enfermedad. Las infecciones virales graves de la piel y la vasculopatía asociada a virus de la varicela zóster (VVZ) reflejan una función importante de la proteína DOCK8, que normalmente se requiere para mantener la integridad de los linfocitos a medida que las células migran a través de tejidos. La pérdida de DOCK8 provoca deficiencias inmunitarias a través de otros mecanismos, incluido un defecto de supervivencia celular. Existen alteraciones en la respuesta de las células dendríticas, lo que explica la susceptibilidad a infección por virus, así como en los linfocitos T reguladores que podrían ayudar a explicar la autoinmunidad en los pacientes. El trasplante de células hematopoyéticas pluripotenciales es por el momento el único tratamiento curativo, mejora el eccema, la alergia y la susceptibilidad a infecciones.

Abstract Combined immunodeficiency (CID) due to DOCK8 deficiency is an inborn error of immunity (IBD) characterized by dysfunctional T and B lymphocytes; The spectrum of manifestations includes allergy, autoimmunity, inflammation, predisposition to cancer, and recurrent infections. DOCK8 deficiency can be distinguished from other CIDs or within the spectrum of hyper-IgE syndromes by exhibiting profound susceptibility to viral skin infections, associated skin cancers, and severe food allergies. The 9p24.3 subtelomeric locus where DOCK8 is located includes numerous repetitive sequence elements that predispose to the generation of large germline deletions and recombination-mediated somatic DNA repair. Residual production DOCK8 protein contributes to the variable phenotype of the disease. Severe viral skin infections and varicellazoster virus (VZV)-associated vasculopathy, reflect an essential role of the DOCK8 protein, which is required to maintain lymphocyte integrity as cells migrate through the tissues. Loss of DOCK8 causes immune deficiencies through other mechanisms, including a cell survival defect. In addition, there are alterations in the response of dendritic cells, which explains susceptibility to virus infection and regulatory T lymphocytes that could help explain autoimmunity in patients. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment; it improves eczema, allergies, and susceptibility to infections.

RESUMO Relatamos um caso de uma paciente de 54 anos com hipertensão intracraniana que apresentava achados atípicos de papiledema unilateral e vasculopatia polipoidal da coroide peripapilar. A investigação levou ao diagnóstico de hipertensão intracraniana idiopática e de um pequeno meningioma incidental. A paciente foi tratada com acetazolamida por via oral, seguida de três injeções intravítreas mensais de bevacizumabe, resultando em inatividade da vasculopatia polipoidal da coroide, redução da exsudação e completa absorção do líquido subretiniano. A apresentação deste caso serve para documentar pela primeira vez vasculopatia polipoidal da coroide associada a papiledema. Ele também demonstra que podem ocorrer anormalidades vasculares da coroide mesmo quando o edema do disco óptico é unilateral, uma manifestação incomum do aumento da pressão intracraniana. O reconhecimento imediato desses achados e seu manejo adequado são essenciais para o tratamento adequado e para prevenção da perda visual irreversível.

ABSTRACT We have reported here the case of a 54-year-old woman with intracranial hypertension that presented with the unique features of unilateral papilledema and peripapillary polypoidal choroidal vasculopathy. Our investigations lead to the diagnosis of idiopathic intracranial hypertension and an incidental small right frontal meningioma. The patient was accordingly treated with oral acetazolamide, followed by three consecutive monthly intravitreal injections of bevacizumab, which resulted in the inactivation of the polypoidal choroidal vasculopathy, marked reduction of lipid exudation, and complete absorption of the subretinal fluid. This case serves as the first documentation of polypoidal choroidal vasculopathy associated with papilledema. It also demonstrates that choroidal vascular abnormalities may occur even when optic disk edema is unilateral, which is an uncommon manifestation of increased intracranial pressure. Prompt recognition of such findings and its appropriate management are essential for adequate treatment and prevention of irreversible visual loss.

Resumen La cocaína pura y la contaminada con levamisol producen múltiples dermatosis, siendo las más frecuentes las lesiones destructivas de línea media y las vasculitis similares a las ANCA. Las bases fisiopatológicas de estas manifestaciones se sustentan en el daño vascular secundario a vasculitis y/o vasculopatía, originado por ambas sustancias y en muchos casos se puede encontrar solapamiento de las formas clínicas, lo que puede llevar a diagnósticos erróneos. Los patrones de positividad de los auto anticuerpos, el patrón de las lesiones cutáneas y el contexto social, serán claves en el abordaje y tratamiento adecuado de estos pacientes.

Abstract Pure cocaine and contaminated cocaine with levamisole produce multiple cutaneous and systemic manifestations, being midline destructive lesions and ANCA-like vasculitis the most frequent ones. The pathophysiological bases of these manifestations are based on secondary vascular damage to vasculitis and/or vasculopathy caused by both substances and in many cases it may be found an overlapping of the clinical forms, which might lead to erroneous diagnoses. The patterns of positivity of the autoantibodies, the pattern of skin lesions and the social context of the patient will be key in the proper approach and management of these patients. The following case describes a patient with cutaneous, nasal and pulmonary manifestations due to cocaine / levamisole consumption. Also, a review of the literature is carried out.

ABSTRACT: Cardiac transplantation is the best alternative for terminal heart failure, achieving good long-term survival and life quality. One of the most important causes of morbidity and mortality is graft failure, which may be secondary, among others, to acute rejection and / or vasculopathy and its presence requires the consideration of all therapeutic alternatives, re transplantation being one of them. The results of survival in cardiac retransplantation are good; however, they present the risks of a more intense immunosuppressive therapy as well as the recurrent development of graft vasculopathy. Therefore, it is considered an option in carefully selected patients given that international experience shows that the survival of retransplantation is lower than in primary cases. We present the case of a 42 year old transplanted patient , who developed graft vascular disease with progressive deterioration of his ventricular function leading to functional class IV. for which a cardiaccardiac retransplantation was performed.

RESUMEN: El Trasplante cardíaco es la mejor alternativa para la insuficiencia cardíaca terminal, logrando buenos resultados de sobrevida y calidad de vida a largo plazo. Una de las causas más importantes de morbimortalidad es la falla del injerto, la que puede ser secundaria, entre otros, a rechazo agudo y/o vasculopatía y su presencia requiere considerar todas las alternativas terapéuticas, dentro de las cuales está el retrasplante. Los resultados de sobrevida en retrasplante cardíaco son buenos. No obstante, los pacientes presentan los riesgos de una terapia inmunosupresora más intensa, así como el desarrollo recurrente de vasculopatía del injerto. Por lo que se considera una opción en pacientes cuidadosamente seleccionados, dado que la experiencia internacional demuestra que la sobrevida del retrasplante es menor que en el primer trasplante. Presentamos el caso de un paciente trasplantado a los 42 años, quien desarrolla una enfermedad vascular del injerto e insuficiencia cardíaca con capacidad funcional IV, por lo cual se decidió realizar un retrasplante cardíaco.

Abstract Livedoid vascular disease (VL), is an occlusive vascular disease that affects the microvasculature, is characterized by being recurrent and non-inflammatory. Its incidence is 1 / 100,000 cases per inhabitant, affecting mostly middle-aged women. Its pathogenesis is unknown, but its thrombotic component stands out, caused by a state of hypercoagulability, which leads to vascular occlusion, and a primary and secondary form must be distinguished. Clinically, painful ulcers are observed at the malleolar level, progressing progressively to characteristic atrophic, pearly whitish and starry healing. We present a clinical case in a male with multiple comorbidities and difficult management, which required multidisciplinary work.

Resumen La vasculopatía livedoide (VL), es una enfermedad vascular oclusiva que afecta la microvasculatura, se caracteriza por ser recurrente y no inflamatoria. Su incidencia es de 1/100.000 casos por habitantes, afectando en su mayoría a mujeres de edad media. Su patogenia se desconoce, pero se destaca el componente trombótico de la misma, causado por un estado de hipercoagulabilidad, que conduce a la oclusión vascular, debiendo distinguirse una forma primaria y una secundaria.Clínicamente se observan úlceras dolorosas a nivel maleolar que evolucionan progresivamente a una cicatrización atrófica, blanquecina nacarada y estrellada característica.Presentamos un caso clínico en un varón con múltiples comorbilidades y difícil tratamiento, el cual requirió un trabajo multidisciplinario.

ABSTRACT Introduction: The systemic sclerosis is an autoimmune disease of the connective tissue where the vasculopathy happens initially and persist during all the disease. The immune component starts since the inflammatory process triggers off but he diminishes until you dwell on the evolutionary course and it is substituted for fibrosis, this ends pathogenic acquires great significance in the process. The index of activity reveals a critical period of the disease. Objective: Evaluating patients' clinical evolution of the index of activity with systemic sclerosis with the applied therapeutics. Methods: The study was quasi-experiences (or secondary prevention). In order to determine if the therapeutic applied scheme decreases symptomatology of its systemic activity. You started in March of the 2013 to March of the 2016, with duration of 24 months. They were 31 patients that split into two groups according to the clinical stages obtained of Comprehensive Development Index. In the group to (clinical stages I and II) 16 patients and in the group B (clinical stages III and IV) 15 patients. The evolution evaluated according to variables of the instrument of evaluation the start, to the six and 12 months itself of once the therapeutic scheme was applied. The T utilized the proof itself, or exact Fisher's proof when moral values were all the same or minor to three, the statistical significance determined in p≥ 0.05 itself. The calculation of the stocking, percentage analysis, and Wilcoxon's proof to know the relation of variables through the time. Results: The therapeutic applied scheme, previous validation, you improved the index of activity of the patients of both groups A and B that is in clinical premature and overdue stages. In the activity moderated for the group A statistical significance for system microvascular (0.023) and respiratory (0.025) to the six months, and to the 12 months’ skin (0.023) and microvascular (0.006). For the intense activity significant improvement to the six months for muscleskelettic (0.005) and rheumatoid positive factor (0.008), to the 12 months’ significant improvement for muscleskelettic (0.004); and examine of laboratory like erythrocyte sedimentation rate (0.008) circulating immune complexes (0.005), and rheumatoid factor (0.003). For the group B in the moderate activity significant improvement for respiratory system existed (0.014), and cardiovascular (0.020) that kept to the 12 months, added up its digestive system (0.008). Evident level improvement of skin (0.004), circulating immune complexes (0.008) and rheumatoid factor were caught up within the intense activity to the 12 months (0.014). Conclusions: Improvement in the index of activity of patients with systemic sclerosis, with the therapeutic scheme applied, with clinical stability and humoral from initial stages of the disease was caught up with.

RESUMEN Introducción: La esclerosis sistémica es una enfermedad autoinmune del tejido conectivo donde ocurre inicialmente la vasculopatía y persiste durante toda la enfermedad. El índice de actividad revela un periodo crítico de la enfermedad. Objetivo: Evaluar la evolución clínica del índice de actividad de pacientes con esclerosis sistémica para determinar si el esquema terapéutico aplicado disminuye los síntomas de actividad sistémica. Métodos: Estudio cuasi experimental terapéutico de 31 pacientes atendidos en el Hospital Lucía Íñiguez Landín de Holguín que se dividieron en dos grupos según las etapas clínicas obtenidas del índice de desarrollo integral desde marzo del 2013 hasta marzo del 2016: el grupo A (etapas clínicas I y II) con 16 pacientes y el grupo B (etapas clínicas III y IV) con 15 pacientes. La evolución se evaluó según variables del instrumento al inicio, a los 6 y 12 meses de aplicado el esquema terapéutico. Se utilizó la prueba T o la prueba exacta de Fisher cuando los valores eran igual a 3 o menores. El cálculo de la media, análisis porcentual y la prueba de Wilcoxon se usaron para conocer la relación de variables en el tiempo. Resultados: El esquema terapéutico aplicado, previa validación, mejoró el índice de actividad de los pacientes de ambos grupos A y B (en etapas clínicas tempranas y tardías). Al evaluar el índice de actividad, en esta serie predominó la actividad moderada, tanto a los 6 como a los 12 meses durante el tratamiento médico. En ambos grupos la mejoría del índice de actividad fue significativa, tanto para la actividad moderada como para la intensa, más notable a partir de los 12 meses con p≤0,05 para el grupo A. Hubo baja susceptibilidad para la mejoría de los sistemas gastrointestinal y respiratorio, en el trascurso de la evaluación de este índice. Conclusiones: Se alcanzó mejoría en el índice de actividad de pacientes con esclerosis sistémica, con el esquema terapéutico aplicado, con estabilidad clínica y humoral desde las etapas iniciales de la enfermedad.

Abstract Background: Wallenberg syndrome (WS) is a classic neurologic disorder secondary to vascular pathology of the vertebrobasilar circulation. Methods: Consecutive patients > 18 years with WS and isolated lateral medullary infarction syndrome were included from two Mexican hospitals. Risk factors, initial signs, symptoms, radiological findings, and acute treatment were evaluated; the prognosis was assessed using the Glasgow Outcome Scale. Results: Twenty-six patients were studied in a 26-year period (1988-2014); 17 patients were men (67%); and the average age was 45 years (range 19-77). Fourteen patients were under 45 years old (54%). The most common risk factors were dyslipidemia (41%) and hypertension (37%). The main initial symptoms were vertigo-dizziness (89%) gait ataxia (70%), and crossed-sensory deficit; and the main signs were crossed-sensitive deficit (93%), Horner syndrome (85%), and nystagmus (82%). In the bivariate analysis, age under 45 years was associated with a vertebral arterial dissection (p = 0.001), and age > 45 with atherothrombotic etiology (p = 0.01). About 96% of patients presented good recovery at an average of 17 months follow-up. Conclusion: Non-atherosclerotic vasculopathy was the main cause of WS-ILBI in young people. The clinical characteristics were similar to those reported in other series with a usually benign prognosis.

Resumen Antecedentes: El síndrome de Wallenberg (SW) es un diagnóstico clásico en neurología, generalmente secundario a patología vascular de la circulación vertebro-basilar. Métodos: Se incluyeron a pacientes mexicanos consecutivos mayores de 18 años de edad con síndrome de SW e infarto bulbar lateral aislado (SW-IBLA) en dos hospitales mexicanos. Se evaluaron los factores de riesgo, signos y síntomas iniciales, hallazgos radiológicos, tratamiento agudo y pronóstico mediante el Glasgow Outcome Scale (GOS). Resultados: Se estudiaron 26 pacientes en un periodo de 26 años (1988-2014); Diecisiete pacientes fueron hombres (67%); el promedio de edad fue de 45 años (rango 19-77). Catorce pacientes fueron menores de 45 años (54%). Los factores de riesgo más frecuentes fueron dislipidemia (41%) e hipertensión arterial (37%). Los principales síntomas al inicio fueron vértigo-mareo (89%) y ataxia para la marcha (70%), así como déficit sensorial cruzado (93%), síndrome de Horner (85%) y nistagmo (82%) a la exploración neurológica. En el análisis bivariado, la edad menor a 45 años se asoció a disección arterial vertebral (p = 0.001), y la edad > 45 a etiología aterotrombótica (p = 0.01). El 96% de los pacientes presentaron buena recuperación en un seguimiento promedio de 17 meses. Conclusión: La vasculopatía no ateroesclerosa fue la principal causa de SW-IBLA en jóvenes. Las características clínicas para esta localización fueron similares a lo reportado en otras series con un pronóstico habitualmente benigno.

RESUMO A constrição de cordão umbilical (CCU) é uma condição infrequente, não bem descrita na literatura, apesar de ser uma importante etiologia observada em fetos natimortos. O objetivo deste estudo foi verificar a ocorrência de CCU como causa de morte fetal e as características etiopatológicas associadas. Para tanto, um estudo retrospectivo transversal foi realizado a partir das informações do banco de dados do Instituto de Patologia de Passo Fundo, durante os anos de 1995 a 2017. Os resultados foram: 1.359 mortes de embriões/fetos, das quais 69 (5,07%) foram devidas a CCU; 60,9% eram do sexo masculino e 39,1%, do feminino. A média de idade das gestantes foi de 27,5 anos; desvio padrão (DP) de ± 7,2 anos. A maioria das mortes ocorreu no segundo trimestre (76,5%), seguido pelo primeiro (14,7%) e terceiro (8,8%). Entre o total de CCU observadas, 87% tiveram ocorrência de apenas uma constrição; 11%, de duas; e 1%, de três ou mais. A presença de malformações congênitas foi encontrada em 20,2% das necropsias; a identificação de sofrimento fetal crônico foi relatada em 71% dos laudos; e características de vasculopatia obstrutiva na análise da microscopia, em 17% dos casos. Em relação às características anatomopatológicas entre os sexos masculino e feminino, nenhuma diferença significativa (p > 0,05) foi encontrada correlacionando idade gestacional dos fetos/embriões, peso ou malformações congênitas. A CCU é uma condição incomum de morte fetal associada a baixo peso fetal e restrição de crescimento. Nossa pesquisa sugere uma possível relação entre a CCU e a vasculopatia obliterativa.

ABSTRACT The umbilical cord constriction (UCC) is an uncommon condition and an important etiology for stillborn fetuses. The main goal of this study was to verify the UCC occurrence as the cause of intrauterine fetal death, the associated etiology and its pathological characteristics. Therefore, a descriptive retrospective cross-sectional study was developed using the database from a Pathology Institute, in Brazil, from 1995 to 2017. The results presented a total of 1,359 embryo/fetus deaths – 69 (5.07%) due to UCC, 60.9% males and 39.1% females. The average age of pregnant women was 27.5 years ± 7.2 years of standard deviation (SD). The majority of deaths occurred during the second trimester (76.5%), followed by the first (14.7%) and third (8.8%) trimesters, respectively. One constriction alone was found in 87% of cases, 11% had two constrictions and only 1% had three or more. The presence of congenital malformations was detected in 20.2% of necropsies, the identification of chronic fetal distress was described in 71% of the technical reports and 17% of the cases had obstructive vasculopathy characteristics in microscopy analysis. Regarding the anatomopathological characteristics between the male and female sexes, no significant difference was found (p > 0.05) correlating gestational age, weight or congenital malformations. UCC was a cause of fetal death found in 5% of the cases, and it was linked to congenital malformations, fetal distress and obliterative vasculopathy.

RESUMEN La constricción del cordón umbilical (CCU) es una condición infrecuente que no está bien descrita en la literatura, a pesar de ser una importante etiología observada en mortinatos. El objetivo de este estudio fue verificar la ocurrencia de CCU como causa de muerte fetal y las características patológicas asociadas. Para ello, se llevó a cabo un estudio retrospectivo transversal con informaciones de la base de datos de un Instituto de Patología, en Brasil, de 1995 hasta 2017. Los resultados fueron: 1.359 muertes de embriones/fetos, de las cuales 69 (5,07%) se debieron a CCU; 60,9% eran del sexo masculino y 39,1%, del femenino. El promedio de edad de las mujeres embarazadas fue de 27,5 anos; desviación estándar de ± 7,2 anos. La mayoría de las muertes ocurrió en el segundo trimestre (76,5%), seguido del primero (14,7%) y del tercero (8,8%). Entre el total de casos de CCU observados, 87% tuvieron sólo una constricción; 11%, dos; y 1%, tres o más. La presencia de malformaciones congénitas fue encontrada en 20,2% de las necropsias; la identificación de sufrimiento fetal crónico fue reportada en 71% de los informes; y características de vasculopatía obstructiva en el análisis de microscopía, en 17% de los casos. Con respecto a las características anatomopatológicas entre los sexos masculino y femenino, no se encontró ninguna diferencia significativa (p > 0,05) correlacionando edad gestacional de los fetos/embriones, peso o malformaciones congénitas. La CCU es una condición rara de muerte fetal asociada a bajo peso fetal y restricción de crecimiento. Nuestra investigación sugiere una posible relación entre la CCU y la vasculopatía obliterativa.

RESUMEN Antecedentes: La esclerosis sistémica (ES) es una enfermedad mediada por el sistema inmunitario, caracterizada por vasculopatía de pequeños vasos y disfunción de los fibroblastos, que da lugar a una mayor producción de matriz extracelular. La enfermedad pulmonar intersticial representa una de las complicaciones más comunes, ya que afecta a cerca del 70% de los pacientes con ES. Objetivo: Evaluar la efectividad de los tratamientos farmacológicos disponibles para la enfermedad pulmonar intersticial asociada a la esclerosis sistémica (EPI-ES) basándonos en las pruebas de función pulmonar y los hallazgos radiológicos. Materiales y métodos: Se llevó a cabo una revisión sistemática de la literatura y un metaanálisis. Se hizo una búsqueda exhaustiva de literatura en EMBASE, MEDLINE PubMed y Cochrane (CENTRAL) con el fin de recopilar los estudios publicados entre enero de 2015 y el 31 de julio de 2019. Los resultados primarios fueron la capacidad vital forzada (CVF), la capacidad de difusión del monóxido de carbono (diffusing capacity of the lungs for carbon monoxide, DLCO), y los hallazgos de la tomografía computarizada de alta resolución (TCAR). Se incluyeron los estudios que utilizaron medicamentos para el tratamiento de la EPI-ES, incluyendo ciclofosfamida (CYC), micofenolato de mofetilo (MMF), nintedanib, pirfenidona o rituximab (RTX). Las medidas de efecto se calcularon con base en los datos disponibles, y se hizo un metaanálisis con estos resultados. Resultados: Encontramos un total de 312 estudios. Después de leer los resúmenes, se seleccionaron 49 estudios para la evaluación del texto completo. Finalmente, se seleccionaron 14 estudios para incluirlos en la revisión final. Se identificaron dos metaanálisis, ocho ensayos clínicos, tres cohortes retrospectivas y un estudio de casos y controles anidado. La evidencia disponible respalda el uso de CYC y MMF como las mejores opciones para el tratamiento de la EPI-ES, siendo el MMF la opción preferida basada en un mejor perfil de seguridad. Otros medicamentos como RTX, pirfenidona y nintedanib muestran potencial como alternativas a la CYC. La calidad global de la evidencia disponible es adecuada ya que parte de estudios por lo general bien diseñados. El metaanálisis se realizó evaluando una disminución > 5% o > 10% de la CVF al comparar los agentes farmacológicos vs. placebo. Los resultados muestran que el uso de agentes farmacológicos se asocia negativamente con el empeoramiento de la CVF. Sin embargo, la alta heterogeneidad limita el número de estudios utilizados durante el análisis cuantitativo, afectando los resultados generales. Conclusiones: Las terapias inmunosupresoras, especialmente la CYC y el MMF, siguen siendo la piedra angular del tratamiento de la EPI-ES, ya que la mayoría de la evidencia muestra una mejoría o una progresión lenta de las pruebas de función pulmonar al usarlas. Sin embargo, se requiere más evidencia con respecto al uso de agentes farmacológicos alternativos, en busca de una mejora de la calidad de vida de estos pacientes.

ABSTRACT Background: Systemic sclerosis (SSc) is an immune-mediated disease characterized by small vessel vasculopathy and fibroblast dysfunction that leads to increased production of extracellular matrix. Interstitial lung disease represents one of the most common complications, by affecting almost 70% of patients with SSc. Objective: To evaluate the effectiveness of the pharmacological treatments available for systemic sclerosis-associated interstitial lung disease (SSc-ILD) based on pulmonary function tests and radiologic findings. Materials and methods: A systematic literature review and meta-analysis were conducted. A thorough literature search was made in EMBASE, PUBMED, and Cochrane CENTRAL to collect studies published between January 2015 and July 31 of 2019. The primary outcomes were forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO), and high-resolution computed tomography findings (HR-CT). Studies using medications for the treatment of SSc-ILD including cyclophosphamide (CYC), mycophenolate mofetil (MMF), nintedanib, pirfenidone, or rituximab (RTX) were included. Effect measures were calculated based on available data, and a meta-analysis was made with these results. Results: We found a total of 312 studies. 49 studies were selected for full-text assessment after reading the abstracts. Finally, 14 studies were selected to be included in the final review. 2 meta-analyses, 8 clinical trials, 3 retrospective cohorts, and one nested case-control study were identified. The available evidence supports the use of CYC and MMF as the best options for the treatment of SSc-ILD, with MMF being the preferred option based on a better safety profile. Other medications such as RTX, pirfenidone, and nintedanib show potential as alternatives to CYC. The overall quality of evidence available is adequate based on generally well-designed studies. Meta-analysis was done by assessing >5% or >10% decrease of FVC when comparing pharmacological agents vs. placebo. Results show that the use of pharmacological agents is negatively associated with the worsening of FVC. However, high heterogeneity limits the number of studies used during quantitative analysis, affecting the overall results. Conclusions: Immunosuppressive therapies remain as the cornerstone of treatment of SSc-ILD, as most evidence show improvement or slow progression of pulmonary function tests by using them, especially CYC and MMF. However, more evidence is required regarding the use of alternative pharmacological agents, in search of an improvement in the quality of life of these patients.

RESUMEN Introducción: La esclerosis sistémica es una enfermedad autoinmune y multisistémica, caracterizada por vasculopatía y fibrosis que afecta principalmente la piel y órganos internos; su morbilidad y mortalidad son las más altas de las enfermedades reumatológicas. Objetivo: Determinar las características sociodemográficas, clínicas y paraclínicas de pacientes adultos con esclerosis sistémica en un centro de referencia en reumatología del noroccidente de Colombia, entre el 2006 y el 2016. Métodos: Estudio descriptivo retrospectivo. La información sobre las variables sociodemográficas, clínicas y paraclínicas se recogió de la revisión de registros médicos. Los datos se procesaron con el paquete estadístico IBM SPSS 22. Las variables cualitativas se expresaron en frecuencias absolutas y relativas y las cuantitativas en media y desviación estándar o mediana y rango intercuartílico, según su distribución. Resultados: Se incluyeron 44 pacientes, predominantemente mujeres (90,9%), con una edad promedio de 59 arios; la variedad más común fue la limitada (61,3%). El 100% de los sujetos presentaron el fenómeno de Raynaud y los sistemas comprometidos con mayor frecuencia fueron: cutáneo (100%), musculoesquelético (59,1%) y gastrointestinal (50%). El 95,5% de los pacientes cumplieron con los criterios diagnósticos ACR/EULAR 2013. Con respecto al perfil inmunológico, el 72,7% de los individuos tenía anticuerpos antinucleares positivos, de los cuales, un 53,1% tenía un patrón centromérico. Conclusiones: Se encontraron características sociodemográficas y clínicas similares en esta cohorte, de acuerdo a lo publicado en la literatura. Los sistemas extracutáneos más frecuentemente involucrados fueron: musculoesquelético, gastrointestinal y pulmonar, que causan una gran parte de la morbilidad asociada, así como una disminución en la calidad de vida.

ABSTRACT Background: Systemic sclerosis is an autoimmune and multisystemic disease characterized by vascular involvement and fibrosis that mainly affects the skin and internal organs; its morbidity and mortality are the highest of rheumatic diseases. Objective: To determine the sociodemographic, clinical, and paraclinical characteristics of adult patients with systemic sclerosis in a reference center in rheumatology in northwestern Colombia, between 2006 and 2016. Methods: A retrospective descriptive study was conducted. Information on sociodemographic, clinical, and paraclinical variables was collected from the review of medical records. The data were processed with the IBM SPSS 22 statistical package. The qualitative variables were expressed in absolute and relative frequencies and the quantitative variables in mean and standard deviation or median and interquartile range, according to their distribution. Results: 44 patients were included, predominantly women (90.9%), with an average age of 59 years; the most common variety was the limited (61.3%). One hundred percent of the subjects presented Raynaud's phenomenon and the most common compromised systems were: cutaneous (100%), musculoskeletal (59.1%), and gastrointestinal (50%). 95.5% of the patients fulfilled the diagnostic criteria ACR / EULAR 2013. Regarding the immunological profile, 72.7% of the individuals had positive antinuclear antibodies, of which 53.1% had a centromeric pattern. Conclusions: Sociodemographic, clinical and similar characteristics were found in this cohort, according to what was published in the literature. The most frequent extracutaneous systems involved were: musculoskeletal, gastrointestinal, and pulmonary, which cause a large part of the associated morbidity, as well as a decrease in quality of life.