MICa/b-dependent activation of natural killer cells by CD64+ inflammatory type 2 dendritic cells contributes to autoimmunity.

Primary Sjögren's syndrome (pSS) is an inflammatory autoimmune disorder largely mediated by type I and II interferon (IFN). The potential contribution of innate immune cells, such as natural killer (NK) cells and dendritic cells (DC), to the pSS pathology remains understudied. Here, we identified an enriched CD16+ CD56hi NK cell subset associated with higher cytotoxic function, as well as elevated proportions of inflammatory CD64+ conventional dendritic cell (cDC2) subtype that expresses increased levels of MICa/b, the ligand for the activating receptor NKG2D, in pSS individuals. Circulating cDC2 from pSS patients efficiently induced activation of cytotoxic NK cells ex vivo and were found in proximity to CD56+ NK cells in salivary glands (SG) from pSS patients. Interestingly, transcriptional activation of IFN signatures associated with the RIG-I/DDX60 pathway, IFN I receptor, and its target genes regulate the expression of NKG2D ligands on cDC2 from pSS patients. Finally, increased proportions of CD64hi RAE-1+ cDC2 and NKG2D+ CD11b+ CD27+ NK cells were present in vivo in the SG after poly I:C injection. Our study provides novel insight into the contribution and interplay of NK and cDC2 in pSS pathology and identifies new potential therapy targets.

Nefropatía endémica mesoamericana: una enfermedad renal crónica de origen no tan desconocido / Mesoamerican nephropathy: A not so unknown chronic kidney disease

Desde el año 2000, la región de Mesoamérica ha presentado una elevada incidencia de casos de enfermedad renal crónica de origen desconocido. Bajo el nombre de nefropatía endémica mesoamericana (NeM) han concurrido numerosas hipótesis incluyendo la deshidratación, el estrés por calor, la exposición a contaminantes ambientales e incluso determinadas infecciones, sin que actualmente exista unanimidad en la etiología de dicha patología. La NeM afecta principalmente a varones jóvenes dedicados a actividades agrícolas con antecedente de exposición a temperaturas especialmente elevadas. Clínicamente cursa con síntomas inespecíficos como febrícula y disuria y, analíticamente, con deterioro de la función renal y alteraciones hidroelectrolíticas. El diagnóstico exige de la realización de una biopsia renal que muestra invariablemente datos de nefritis tubulointersticial, principalmente crónica. A pesar de que la NeM condiciona una elevada morbimortalidad en las regiones endémicas, no existe un tratamiento específico, por lo que la prevención, basada en disminuir la exposición a elevadas temperaturas y asegurar el correcto estado de hidratación son de gran importancia. En la presente revisión, y basándonos en un caso clínico, actualizamos la evidencia disponible sobre un problema de salud pública con relevantes consecuencias renales. (AU)

From 2000, Mesoamerican region has reached an important rate of chronic kidney disease of unknown etiology. Under the name of Meroamerican Nephropathy (MeN) several hypotheses (including dehydration, heat stress, environmental or toxic exposure or even infections) have tried to explain the etiology this new disease. MeN affects young men, agricultural workers exposed to high temperatures. MeN courses with unspecific symptoms as low-grade fever and dysuria and progressive kidney disease with impaired renal function and hydroelectrolyte disturbances. The diagnosis requires kidney biopsy showing tubule-interstitial nephritis (usually at chronic stage). Although MeN conditions a high morbi-mortality in endemic regions, there is a lack of specific treatment and only preventive measures have demonstrated some effect of prognosis (avoid heat stress, constant hydration). In this review we aim to summarize the available information of MeN, illustrating the information in a case report. (AU)

Tumor-Associated Granulomas Preceding a Diagnosis of Thoracic Sarcoidosis: A Retrospective, Single-Center Cohort Study.

There is a relationship between systemic sarcoidosis (SS) and malignancy. Sarcoidosis results from an exaggerated immune response in genetically susceptible individuals. In oncologic patients with sarcoidosis, tumoral antigens and antineoplastic treatment are considered potential triggering factors. The observation of a patient with granulomas in a parotid carcinoma who later developed SS led us to review the previous tumors of patients with SS. The aim of the study is to see whether granulomas were already present in the tumors that preceded sarcoidosis. We identified 196 sarcoidosis patients, 47 of whom had previously had a tumor. We were able to review 29 cases, 12 of which showed tumor-associated granulomas (TAGs) (41.4%). This ratio is much higher than that of the normal population (4.4-13.8). We analyzed five control patients without sarcoidosis for each tumor. In conclusion, we observed an increased number of TAGs in patients who later developed SS. This finding reinforces a pathogenic relationship between SS and neoplasia. The histology of tumors in patients with SS should be reviewed in an attempt to identify granulomas.

Mesoamerican nephropathy: A not so unknown chronic kidney disease. / Nefropatía endémica mesoamericana: una enfermedad renal crónica de origen no tan desconocido.

From 2000, Mesoamerican region has reached an important rate of chronic kidney disease of unknown etiology. Under the name of Meroamerican Nephropathy (MeN) several hypotheses (including dehydration, heat stress, environmental or toxic exposure or even infections) have tried to explain the etiology this new disease. MeN affects young men, agricultural workers exposed to high temperatures. MeN courses with unspecific symptoms as low-grade fever and dysuria and progressive kidney disease with impaired renal function and hydroelectrolyte disturbances. The diagnosis requires kidney biopsy showing tubule-interstitial nephritis (usually at chronic stage). Although MeN conditions a high morbi-mortality in endemic regions, there is a lack of specific treatment and only preventive measures have demonstrated some effect of prognosis (avoid heat stress, constant hydration). In this review we aim to summarize the available information of MeN, illustrating the information in a case report.

Cytologic Features of Lipogranulomatous Reaction in an Axillary Sentinel Lymph Node.

INTRODUCTION: Multinucleated giant cells (MGC) are a rare finding when evaluating axillary sentinel lymph nodes. Some are described as foreign body-type MGC accompanied by foamy macrophages. They have been rarely reported in nodes from patients in which a previous breast biopsy was performed. The tissue damage induced by biopsy results in secondary changes including fat necrosis and hemorrhage that can migrate to axillary nodes. In this report, we illustrate a lipogranulomatous reaction in cytologic samples obtained during a sentinel lymph node examination of a woman previously biopsied because of breast carcinoma. We have found no previous cytologic descriptions and consider it an interesting finding that should be known to avoid diagnostic misinterpretations. CASE: A 51-year-old woman underwent mastectomy of the right breast with a sentinel lymph node biopsy at our medical center. One month before, a control mammography revealed suspicious microcalcifications and a vacuum-assisted breast biopsy resulted in a diagnosis of high-grade intraductal carcinoma with comedonecrosis. Surgery with a sentinel lymph node biopsy was performed. The sentinel node was processed as an intraoperative consultation. Frozen sections and air-dried Diff-Quik stained samples were obtained. They showed abundant lymphocytes with MGC and tumoral cells. MGC showed ample cytoplasm with evident vacuoles of variable size. Occasional hemosiderin-laden macrophages were also present. The complete histologic analysis and immunohistochemical studies revealed no malignant cells. Histologic analysis showed, in subcapsular location, occasional MGC phagocyting lipid droplets. Hemosiderin-laden macrophages were a common finding. CONCLUSION: Lipogranulomas may appear at axillary sentinel lymph nodes because of fat necrosis induced by previous breast biopsy. The most important consideration is not confounding MGC with epithelial cell clusters. This can occur with not well-processed samples, especially if unmounted.

Mesoamerican nephropathy: A not so unknown chronic kidney disease.

From 2000, Mesoamerican region has reached an important rate of chronic kidney disease of unknown etiology. Under the name of Meroamerican Nephropathy (MeN) several hypotheses (including dehydration, heat stress, environmental or toxic exposure or even infections) have tried to explain the etiology this new disease. MeN affects young men, agricultural workers exposed to high temperatures. MeN courses with unspecific symptoms as low-grade fever and dysuria and progressive kidney disease with impaired renal function and hydroelectrolyte disturbances. The diagnosis requires kidney biopsy showing tubule-interstitial nephritis (usually at chronic stage). Although MeN conditions a high morbi-mortality in endemic regions, there is a lack of specific treatment and only preventive measures have demonstrated some effect of prognosis (avoid heat stress, constant hydration). In this review we aim to summarize the available information of MeN, illustrating the information in a case report.

Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage: an autopsy study with clinical correlation and review of the literature.

Pulmonary megakaryocytes participate in the pathogenesis of lung damage, particularly in acute lung injury. Although megakaryocytes are not mentioned as a characteristic histologic finding associated to pulmonary injury, a few studies reveal that their number is increased in diffuse alveolar damage (DAD). In this autopsy study, we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute lung injury (7.61 ± 5.59 megakaryocytes per 25 high-power fields vs. 1.14 ± 0.86 for the control group, p < 0.05). We analyzed samples of 18 patients, most of whom died after prolonged disease and use of mechanical ventilation. Most patients showed advanced DAD and abnormal coagulation parameters with high levels of fibrinogen, D-dimers, and variable thrombocytopenia. For comparison, pulmonary samples from a group of 14 non-COVID-19 patients dying with DAD were reviewed. They showed similar pulmonary histopathologic findings and an increase in the number of megakaryocytes (4 ± 4.17 vs. 1.14 ± 0.86 for the control group, p < 0.05). Megakaryocyte count in the COVID-19 group was greater but did not reach statistical significance (7.61 ± 5.59 vs. 4 ± 4.17, p = 0.063). Regardless of the cause, pulmonary megakaryocytes are increased in patients with DAD. Their high number seen in COVID-19 patients suggests a relation with the thrombotic events so often seen these patients. Since the lung is considered an active site of megakaryopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response.

Enfermedad ampollosa autoimnume de cavidad oral: pénfigo vulgar. A propósito de un caso clínico / Blistering autoimmune disease of the oral cavity: pemphigus vulgaris. Case report

Las enfermedades ampollosas de cavidad oral son un grupo de enfermedades poco frecuente y de carácter autoinmune. Se conocen seis formas de pénfigo: vulgar, vegetante, inmunoglobulina A, foliáceo, eritematoso y paraneoplásico. Este tipo de lesiones pueden presentarse de los 50 a los 65 años de edad, existiendo una predilección por el sexo femenino. La manifestación inicial se produce en la cavidad oral como ulceraciones múltiples precedidas por ampollas que se rompen y luego se extienden a otras membranas mucosas y la piel, y en ciertas ocasiones a nivel esofágico, cursando este con odinofagia y disfagia. Es fundamental el diagnóstico, así como un tratamiento precoz de estos pacientes. Actualmente se obtiene un mejor pronóstico y evolución en aquellos pacientes que presentan una respuesta rápida al tratamiento con corticoides

Blistering diseases of the oral cavity are rare and autoimmune disease. Six types of penis are characterized: vulgar, vegetative, immunoglobulin A, foliaceous, erythematous and paraneoplastic. This type of injury can occur at 50 years of age, with a predilection for females. The initial manifestation occurs in the oral cavity as multiple ulcerations preceded by blisters that rupture and then spread to other mucous membranes and skin, and sometimes at the esophageal level, with odynophagia and dysphagia. It is fundamental the diagnosis as well as an early treatment of these patients, currently there is a better prognosis and a better evolution in those patients who present a rapid response to treatment with corticosteroids

Lesiones cerebrovasculares asintomáticas y su relación con factores de riesgo vascular en pacientes con insuficiencia renal crónica terminal en hemodiálisis / Asymptomatic cerebrovascular lesions and their relationship to vascular risk factors in patients with end stage renal disease on hemodialysis program

Objetivo: Determinar la relación entre los factores de riesgo vascular y la presencia de lesiones cerebrovasculares en pacientes con insuficiencia renal crónica terminal (IRCT) en programa de hemodiálisis. Material y Métodos: Se realizó un estudio prospectivo, transversal y analítico en el Hospital Nacional Essalud Carlos Alberto Seguín Escobedo de Arequipa, en 106 pacientes con IRCT en programa de hemodiálisis, sin historia de patología neurológica previa. Se realizó una resonancia magnética nuclear cerebral para detectar lesiones cerebrovasculares (lesiones de sustancia blanca y/o infartos cerebrales silentes). Se determinó los factores de riesgo vascular ôtradicionalesõ y ôno tradicionalesõ mediante revisión de historias clínicas y cuestionarios. Resultados: Se encontró lesiones cerebrovasculares asintomáticas en 86 pacientes (81,1%) de los cuales 69 pacientes (80,2%) tuvieron ambas lesiones (lesión de sustancia blanca e infarto cerebral silente). Los factores ôtradicionalesõ de riesgo vascular que tuvieron una relación significativa (p < 0,05) con la presencia de lesiones cerebrovasculares asintomáticas fueron edad avanzada, hipertensión arterial, diabetes mellitus, hipercolesterolemia, elevación de LDL-c e hiperuricemia; y, de los factores ôno tradicionalesõ fueron trastornos del fósforo sérico, hipoalbuminemia y elevación de proteína C reactiva. El mayor tiempo en hemodiálisis también tuvo una relación significativa (p<0,05) con la presencia de lesiones cerebrovasculares. Conclusión: Se concluye que existe relación entre los factores de riesgo vascular con la presencia de lesiones cerebrovasculares asintomáticas en los pacientes evaluados en este estudio.

Objective. To determine the relationship between traditional and non-traditional vascular risk factors and the presence of asymptomatic cerebrovascular lesions on end stage renal disease (ESRD) patients in hemodialysis. Material and Methods. A prospective, cross-sectional and analytical study was carried on in Carlos Alberto Seguin Escobedo Hospital, Arequipa, on 106 patients with ESRD on hemodialysis and with no previous neurological event. All patients underwent a magnetic resonance imaging of the brain in order to detect cerebrovascular lesions (white matter lesions and/or silent brain infarcts). Traditional and non-traditional vascular risk factors were identified by reviewing medical records and filling out questionnaires. Results. Asymptomatic cerebrovascular lesions occurred in 86 patients (81,1%), both lesions (white matter lesions and silent brain infarcts) occurred in 69 (80,2%) of patients. Traditional vascular risk factors that correlated (p<0,05) with the presenceof asymptomatic cerebrovascular lesions were: old-age, hypertension, diabetes, hypercholesterolemia, elevation of low density lipoprotein, hyperuricemia, serum phosphate disorder, hypoalbuminemia and elevation of the C-reactive protein. Time in hemodialysis too correlated with the presence of cerebrovascular lesions (p < 0,05). Conclusion. There was a significant relationship between vascular risk factors and asymptomatic cerebrovascular lesions in ESRD patients.