ABSTRACT Introduction the autopsy is an essential medical procedure; however, its use has declined over the decades. In autoimmune and rheumatological diseases, anatomical and microscopic diagnosis is critical to diagnose of the cause of death. For this reason, our objective is to describe the cause of death in patients diagnosed with autoimmune and rheumatic diseases who underwent an autopsy in a Pathology reference center in Colombia. Materials and methods a retrospective and descriptive study of autopsy reports. Results between January 2004 and December 2019, 47 autopsies of patients with autoimmune and rheumatological diseases were performed. Systemic lupus erythematosus and rheumatoid arthritis were the most common diseases. The leading cause of death was related to infections, being opportunistic infections in the majority of the cases. Conclusions our autopsy-based study was focused on patients with autoimmune and rheumatological conditions. Infections are the leading cause of death, particularly opportunistic infections, diagnosed mainly by microscopy. Thus, the autopsy should continue to be considered the “gold standard” to determine the cause of death in this population. procedure however decades reason Colombia reports 200 2019 4 performed cases autopsybased based conditions microscopy Thus gold standard population 20 201 2

BACKGROUND Topical treatment of New World cutaneous leishmaniasis can be affected by bacterial coinfection, hyperkeratosis, and transdermal drug delivery. OBJECTIVE The aim of this work was to evaluate the therapeutic response and safety of the topical, sequential use of antiseptic, keratolytic, and pentamidine isethionate (PMD) creams (3-PACK kit) on CL-infected BALB/c mice. METHODS A 0.5% chlorhexidine solution (CGH), 10% salicylic acid (SA), and 3% or 6% PMD were used as antiseptic, keratolytic, and antileishmanial drugs, respectively. During the first seven days, antiseptic, followed by 10% SA gel and PMD cream, were applied topically. Subsequently, treatment was performed only with the antiseptic and PMD creams. Skin irritation, reduction of lesion size (mm2), and parasitic load were observed until 30 days of treatment were completed. FINDINGS The 3-PACK treatment using 6% PMD induced a complete lesion reduction in 3/6 mice and a partial reduction in 1/6 mice, with no parasites observed. In contrast, CGH and SA alone, along with the vehicle, were not effective (p < 0.05). Moderate to severe erythema was observed at the application site. MAIN CONCLUSION The topical 3-PACK using 6% PMD was 67% effective in the treatment of CL by Leishmania (Viannia) braziliensis. Currently, work is ongoing to improve PMD isethionate formulation and to determine a dose-response.

Introducción: Las nanoemulsiones son excelentes sistemas de transporte y entrega de fármacos. La ftalocianina de aluminio clorada (PcAlCl) en terapia fotodinámica constituye una alternativa de tratamiento en leishmaniasis cutánea. Objetivo: Determinar la difusión y retención en piel humana de la PcAlCl contenida en una nanoemulsión (nano-PcAlCl) para su optimización en formulaciones tópicas. Materiales y métodos: Se prepararon y caracterizaron fisico-químicamente dos formulaciones (nano-PcAlCl y solución-PcAlCl) y sus vehículos sin-PcAlCl. La permeación se determinó en ensayos en celdas de difusión de Franz y la retención por el método de la cinta adhesiva. La concentración de PcAlCl fue determinada fluorométricamente (nM/cm2). Biopsias de piel fueron analizadas histotécnicamente. Resultados: El tamaño promedio, el potencial Z y el índice de polidispersión de la nano-PcAlCl en agua fue de 132,9 nm, -19,23 y 0,14 y diluida en PBS fue 125,33 nm, -13,69 y 0,139. Las concentraciones de PcAlCl se mantuvieron estables. La PcAlCl no atravesó la piel y fue retenida en sus capas, en estrato córneo y epidermis+dermis con valores de 44,17 nM y 8,48 nM postratamiento con nano-PcAlCl, y 96,90 nM y 9,80 nM postratamiento con solución-PcAlCl. Esta última promovió mayor retención en estrato córneo y ambas formulaciones promovieron similar retención en epidermis+dermis. Se observó desprendimiento del estrato córneo y fragmentación del colágeno. Conclusión: La PcAlCl no atravesó la piel, se retuvo en estrato córneo y epidermis+dermis. Se sugiere realizar ensayos de permeación utilizando piel humana desprovista de estrato córneo y ensayos de distribución en animales con leishmaniasis cutánea.

Introduction: The nanoemulsions constitute excellent drug delivery systems for carrying and delivering active drugs. Chloroaluminum phthalocyanine (ClAlPc) in photodynamic therapy constitutes an interesting alternative in cutaneous leishmaniasis treatment. Objective: To determine the diffusion and retention of ClAlPc contained in a nanoemulsion (nano-ClAlPc) in human skin membranes for optimization of topical formulations. Materials and methods: Two formulations (ClAlPc-nano- and ClAlPc-solution) and vehicles without ClAlPc were prepared and physicochemical characterized. The permeation was tested in Franz-diffusion cells and the retention by the tape stripping method. ClAlPc concentration was determined fluorometrically (nM/cm2). Skin biopsies were analyzed by histologic technics. Results: The ClAlPc-nano average size, zeta potential and polydispersity index diluted in water was 132.9 nm, -19.23 and 0.14 and diluted in phosphate-buffer-saline was 25.33 nm, -13.69 and 0.139. ClAlPc maintains its stability in each formulation. ClAlPc was unable to pass completely through the skin; it was retained in the different skin layers. A ClAlPc retention in stratum corneum and epidermis+dermis was observed with values of 44.17 nM and 8.48 nM after ClAlPc-nano treatment and 96.90 nM and 9.80 nM after ClAlPc-solution treatment. The ClAlPc-solution promoted greater retention in stratum corneum and both formulations showed similar ClAlPc-retention in epidermis+dermis. Histological changes as stratum corneum detachment and collagen-fragmentation were observed. Conclusion: ClAlPc was not able to cross completely the skin, it was retained in stratum corneum and epidermis+dermis Human permeation test using skin membranes without stratum corneum, and distribution assays in cutaneous leishmaniasis-infected animals, are suggested.

Introdução: as nanoemulsões são excelentes sistemas de transporte e entrega de fármacos. A ftalocianina de alumínio clorada (PcAlCl) em terapia fotodinâmica constitui uma alternativa de tratamento em leishmaniose cutânea. Objetivo: determinar a difusão e retenção em pele humana da PcAlCl contida em uma nanoemulsão (nano-PcAlCl) para sua otimização em formulações tópicas. Materiais e métodos: se prepararam e caracterizaram fisico-quimicamente duas formulações (nano-PcAlCl e solução-PcAlCl) e seus veículos sem-PcAlCl. A permeação determinou-se em ensaios em celas de difusão de Franz e a retenção pelo método da fita adesiva. A concentração de PcAlCl foi determinada fluorometricamente (nM/cm²). Biopsias de pele foram analisadas histotecnicamente. Resultados: o tamanho médio, o potencial Z e o índice de polidispersão da nano-PcAlCl em água foi de 132,9 nm, -19,23 e 0,14 e diluída em PBS foi 125,33 nm, -13,69 e 0,139. As concentrações de PcAlCl mantiveram-se estáveis. A PcAlCl não atravessou a pele, foi retido em suas capas. A PcAlCl foi retida em estrato córneo e epiderme+derme com valores de 44,17 nM e 8,48 nM pós-tratamento com nano-PcAlCl e 96,90 nM e 9,80 nM pós-tratamento com solução-PcAlCl. A solução-PcAlCl promoveu maior retenção em estrato córneo e ambas as formulações promoveram similar retenção em epiderme+derme. Observou-se desprendimento do estrato córneo e fragmentação do colágeno. Conclusão: a PcAlCl não atravessou a pele; reteve-se em estrato córneo e epiderme+derme. Sugere-se realizar ensaios de permeação utilizando pele humana desprovida de estrato córneo e ensaios de distribuição em animais com leishmaniose cutânea.

Introducción: describir tres casos fatales de tuberculosis meníngea y establecer correlación clinicopatológica. Materiales y métodos: revisión de protocolos de autopsia entre enero 1 y junio 30 de 2010 en el Departamento de Patología de la Universidad Industrial de Santander (UIS). Entre 121 protocolos de necropsias se encontraron 3 casos de tuberculosis meníngea, de los cuales se revisaron historias clínicas, preparaciones histopatológicas y fotografías. Resultados: tres casos de adultos con edad promedio de 39 años, sin inmunosupresión con tuberculosis meníngea. Las manifestaciones clínicas fueron cefalea, vómito, fiebre, disartria, compromiso de pares craneales, alteraciones motoras y del estado de conciencia. Conclusiones: la tuberculosis meníngea es la forma más grave de la enfermedad, con desenlace fatal en casos no diagnosticados. El bajo índice de sospecha y la similitud con otras infecciones del sistema nervioso central, no permiten diagnostico precoz ni tratamiento oportuno. Salud UIS 2012; 44 (1): 57-66

Introduction: to describe three fatal cases of tuberculous meningitis and to establish clinical pathological correlation. Materials and methods: Revision of autopsy protocols between 01 january and june 30 of 2010 in the Department of Pathology of the Industrial University of Santander (UIS). Between 121 protocols of autopsies were 3 cases of tuberculous meningitis, of which clinical histories, histopathological slides and photographies were rewieved. Results: three cases of adults with age average of 39 years, without inmunosupresión with tuberculous meningitis. The clinical manifestations were migraine, vomit, fever, disartria, commitment of cranial nerves, motor alterations and disorders of consciousness. Conclusions: the tuberculous meningitis is the most serious form of the disease, with fatal course in nondiagnosed cases. The low index of suspicion and the similarity with other infections of the central nervous system, do not allow early diagnostic and nor opportune treatment. Salud UIS 2012; 44 (1): 57-66

Introducción: Los tumores carcinoides son las neoplasias más frecuentes del apéndice cecal, se caracterizan por un crecimiento lento y curso clínico asintomático, su incidencia se calcula en 1-2 casos por cada 100,000 habitantes, se encuentran en menos del 1% de las apendicetomías y se presentan con mayor frecuencia en mujeres entre la cuarta a quinta época de la vida. Por lo general se trata de lesiones pequeñas que se diagnostican luego de la apendicetomía. Metodología El presente trabajo corresponde a una descripción de casos de tumor carcinoide del apéndice cecal, realizado en el laboratorio de patología MEGA, de la Clínica Ardila Lulle (CAL) que incluye revisión de protocolos de especímenes quirúrgicos analizados entre enero 1 de 2000 y diciembre 31 de 2010. Resultados: Durante el periodo propuesto se encuentran cuatro casos de tumor carcinoide confinado al apéndice cecal en cuatro mujeres jóvenes. Tres de las lesiones presentan patrón histológico tipo A o insular y el restante un patrón tipo B o trabecular, en todos los casos se documentó reactividad con las sales de plata con la coloración de Fontana Masson y en los cuatro se encontró positividad con el marcador neuroendocrino cromogranina. Conclusión: Los tumores carcinoides de apéndice son lesiones de origen neuroendocrino, la mayoría circunscritas a la punta del órgano y de curso clínico indolente, sin embargo algunos de estos tumores tienen un comportamiento agresivo, que depende de su tamaño y de la actividad mitótica de sus células, por lo que se recomienda incluir en la evaluación diagnostica la cromogranina y el Ki67, marcadores neuroendocrino y de proliferación celular. Salud UIS 2011; 43 (2): 203-210

Introduction: The carcinoids tumours are the most common neoplasm of the cecal appendix, are characterized by a slow growth and asymptomatic clinical course, its incidence is estimated at 1-2 cases per 100.000 inhabitants, are less than 1% of appendicectomies and occur most often in women between the fourth o fifth decade of life. Usually these are small lesions diagnosed after appendicectomy. Methodology: This work belongs to a description of cases of carcinoid tumor of cecal appendix, conduced in the MEGA anatomic pathology laboratory of Carlos Ardila Lulle Clinic (CAL), wich includes protocols review of surgical specimens analized between January 1, 2000 and December 31, 2010. Results: During the proposed period are four cases of carcinoid tumor confined to the cecal appendix in four young women. Three of the lesions have the A histological type or insular pattern, and the remainder have the B histological type or trabecular pattern, in all cases documented reactivity with silver salts with Masson-Fontana stain and all four were found positive with the neuroendocrine marker chromogragin. Conclusion: The carcinoid tumors of the apenddix are lesions of neuroendocrine origen, most of them located at the tip of the organ, and having a indolent clinical course; however some of these tumors have an aggressive behavior, which depends on its size and the mitotic activity of its cells, that's the reason why the diagnostic evaluation of neuroendocrine markers like chromogranin, and Ki67 (proliferation cell index) are recommended. Salud UIS 2011; 43 (2): 203-210

Introducción: El hemangioendotelioma hepático infantil es el tumor primario del hígado más común en la infancia. Se presenta en pacientes menores de 6 meses, puede ser diagnosticado in útero, donde las grandes comunicaciones arteriovenosas producen hidrops fetal no inmune. Objetivo: Se describe un caso de un feto muerto con un hemangioendotelioma hepático infantil y se realiza una discusión sobre este tema. Caso clínico: Producto de un embarazo de 33 semanas de gestación de una mujer de 23 años, la ecografía obstétrica evidencio hidrops fetal secundario a presencia de tumor hepático, el paciente fallece minutos después de su nacimiento. En la necropsia se evidencia feto de sexo masculino de 3250 gr de peso, con tumor hepático de características sólidas, cuyo examen histopatológico corresponde con un hemangioendotelioma hepático infantil. Conclusiones: Se presenta el estudio anatomopatológico de una autopsia perinatal realizada a un feto con tumor congénito, un hemangioendotelioma hepático infantil que produjo hidrops fetal no inmune. Salud UIS 2010; 42: 123-126

Introduction: Infantile hepatic hemangioendothelioma (HHI) is the primary liver tumor more common in childhood. Usually occurs before the 6 months of age. These tumors can be diagnosed in utero, where the large arteriovenous shunting cause non-inmune hydrops fetalis. Objetive: Describe a case of a dead fetus with a hepatic hemangioendothelioma and a discussion on this topic is done. Clinical case: Product of pregnancy of 33 weeks of gestation in a 23 years old woman, obstetrical ultrasound evidenced fetal hydrops secondary to the presence of liver tumor, the patient died minutes after birth. The necropsy showed a male fetus of 3250gr in weight, with a liver tumor with solid features, which histopathological examination corresponds to a HHI. Conclusions: We report the pathological study of a perinatal autopsy done to a fetus with a congenital tumor, an HHI that cause non-inmune hydrops fetalis. Salud UIS 2010; 42: 123-126.

Introducción: La rabia es una zoonosis letal producida por un virus ARN del género Lyssavirus que se trasmite al hombre por la saliva del animal infectado por mordedura, contaminación de una herida abierta, arañazo, abrasión o laceración de una membrana mucosa o tejido nervioso infectado. Se ha comprobado, además, la transmisión a humanos por inhalación del virus de la rabia presente en aerosoles suspendidos en el aire de cavernas en las que habitan gran cantidad de murciélagos, así como en accidentes de laboratorio y mediante el trasplante de órganos infectados con el virus. Este penetra desde la herida a las terminaciones nerviosas y por transporte axonal retrogrado ingresa al sistema nervioso central, cuyo compromiso explica las manifestaciones clínicas de la enfermedad en sus formas encefalítica y paralitica, la última de las cuales se caracteriza por pérdida de la fuerza iniciada en la extremidad mordida y se extiende a las demás extremidades como una parálisis flácida, semejando un Síndrome de Guillain Barré (SGB). Objetivo: Presentar un caso de una paciente, residente de una zona urbana de Barrancabermeja, muerta por rabia humana cuyo cuadro clínico fue diagnosticado como un SGB y su necropsia evidenció una encéfalo-mielo- neuritis rábica. Resultado: Mujer adulta con manifestaciones clínicas de cuadriparesia flácida, disfagia y disnea, diagnosticada como SGB, hospitalizada en la unidad de cuidados intensivos de una institución de salud de III nivel de la ciudad de Bucaramanga quien fallece 23 días después de iniciar su sintomatología neurológica. Por interrogatorio a familiares se estableció el antecedente de mordedura por murciélago 2 meses antes y por estudio de autopsia se diagnosticó encefalitis rábica. Discusión: El presente informe busca llamar la atención sobre un nuevo caso de rabia humana trasmitida por quirópteros en una zona urbana del departamento de Santander, Colombia para que se realicen actividades preventivas que eviten la ocurrencia de nuevos pacientes y alertar al personal médico para que actúe de manera diligente y precoz ante cualquier posible accidente rábico, ya que el manejo inadecuado de los mismos puede favorecer un nuevo caso de la fatal enfermedad. También, dada la frecuencia de casos de SGB en nuestras instituciones hospitalarias contemplar en su diagnóstico diferencial la rabia en su forma paralítica e insistir en los antecedentes de mordedura por murciélagos u otros animales así haya sido meses o incluso años antes. Salud UIS 2010; 42: 139-151

Introduction: Rabies is fatal zoonoses caused by an RNA virus of the gender Lyssavirus, it is transmitted to humans through the saliva of infected animal bite, contamination of an open wound, scratch, abrasion or laceration of a mucous membrane or infected nervous tissue. It has been found further transmission to humans by inhalation of rabies virus present in aerosol suspended in the air of caves where bats live in large numbers, as well as in laboratory accidents and by transplanting organs infected with the virus. This penetrates from the injury to the nerve endings and by retrograde axonal transport enters to the Central Nervous System whose commitment explains the clinical manifestations in its encephalitic and paralytic forms, the latter of which is characterized by loss of force initiated in the bitten limb and spread to the other limns as a flaccid paralysis, resembling a Guillain Barré syndrome (GBS). Objective: To present a case of a patient female, resident from a urban area of Barrancabermeja, died of rabies, whose clinic picture was diagnosed as a GBS and necropsy revealed a rabies encephalitis. Results: Adult female with clinical features of flaccid quadriparesis, dysphagia, and dyspnea, diagnosed as GBS and hospitalized in the intensive care unit of a health institution level III of the city of Bucaramanga, who died 23 days after starting his neurological symptoms. By questioning her family it was established a bat bite 2 months before and autopsy determined rabies encephalitis. Discussion: This report seeks to draw attention on a new episode of human rabies transmitted by bats in an urban area of the department of Santander, Colombia to carry out preventive activities to prevent the occurrence of new cases and alert medical personnel to act diligently and early to any possible rabies accident, and that improper handling of these can contribute to a new case of fatal disease. Also, given the frequency of cases of GBS in our hospitals to bear in mind in its differential diagnosis, the rabies in its paralytic form and insist on a history of being bitten by bats or other animals thus have been months or even years before. Salud UIS 2010; 42: 139-151.

Introducción: Los teratomas sacrococcígeos, constituyen una neoplasia que pese a su baja frecuencia, es una de las más comunes en neonatos. Se describe un caso de un feto muerto con hallazgos histopatológicos de un teratoma sacro coccígeo inmaduro.Pacientes y Métodos: Mujer de 26 años de edad en su cuarto embarazo de 32 semanas de gestación, quien presenta amenaza de parto pre término. Se le realiza una ecografía obstétrica que informa la presencia de una masa sacra fetal, e hidrops fetal. Se realizó cesárea y se obtiene un óbito fetal de sexo femenino. El estudio anatomopatológico evidenció un teratoma sacrococcígeo inmaduro. Conclusiones: En los teratomas sacrococcígeos fetales, el desarrollo de hidrops fetal, insuficiencia cardiaca y gran tamaño tumoral son indicadores de mal pronóstico. El diagnóstico prenatal, la planificación del parto, la estabilización perinatal y la resección quirúrgica del tumor, pueden hacer posible la sobre vida en estos pacientes. Salud UIS 2010; 42: 127-131

Introduction: Sacrococcygeal teratomas are neoplasm that despite their low frequency, are one of the most common in newborns. We describe a case of a dead fetus with an immature sacrococcygeal teratoma, its radiological and histological findings. Patients and Methods: A 26 years old woman in the fourth pregnancy of 32 weeks' of gestation, who presented the threat of pre-term birth. We performed obstetric ultrasound reporting the presence of a fetal sacral mass and fetal hydrops. Caesarean section was run and got a female fetal death. Pathologic study showed immature sacrococcygeal teratoma. Conclusions: In fetal sacrococcygeal teratomas, the development of fetal hydrops, heart failure and large tumor size are indicators of poor prognosis. Prenatal diagnosis, planning delivery, the postnatal stabilization period and surgical resection of the tumor, can make survival possible in these patients. Salud UIS 2010; 42: 127-131.