Early clinical, histological, and immunohistochemical findings in suspected acute graft-versus-host disease and their association with patient outcomes.

BACKGROUND/OBJECTIVES: Acute graft-versus-host disease (aGVHD) is a serious condition after allogeneic hematopoietic stem cell transplantation (HSCT), frequently involving skin, gut, and liver. It can be difficult to diagnose early, yet this is vital for adequate management. We sought to identify initial clinical and histopathological features in children with suspected GVHD and the association with clinical course and outcomes. METHODS: Retrospective study of patients with skin biopsies for suspected aGVHD from 2006 to 2016. We collected demographic and clinical information, histologic, and immunohistochemical (IHC) findings, and outcomes during follow-up. Bivariate and multivariate analyses were done to identify risk factors associated with remission, development of severe/life-threatening aGVHD, and mortality. RESULTS: We included 42 patients, 15 females. Skin manifestations occurred 51 days (median) after HSCT. On biopsy, 76.2% had mild (stage 1-2) skin aGVHD; during the course of the disease, severity and systemic involvement increased to global grade III/IV in 66.6%. All patients received treatment; 15 are in remission from aGVHD and 23 have died. Histologic features were diagnostic in 83.3%. On bivariate and multivariate analysis, we identified initial clinical and histologic findings that were associated with the measured outcomes: odds of remission from aGVHD were increased when focal vacuolar changes were found on skin biopsy (OR 6.028; 95%CI:1.253-28.992) but decreased by initial hepatic aGVHD (OR 0.112; 95%CI: 0.017-0.748); severe/life-threatening aGVHD was associated with initial gastrointestinal aGVHD (OR 6.054; 95%CI:1.257-29.159); and odds of mortality were decreased with male donor (OR 0.056; 95%CI:0.004-0.804), nulliparous female donor (OR 0.076; 95%CI:0.009-0.669), and focal vacuolar changes on skin biopsy (OR 0.113; 95%CI:0.017-0.770). CONCLUSIONS: We found novel indicators predictive of remission, severity, and mortality in children with aGVHD. Further studies of this condition in children are needed.

Usefulness of the skin biopsy as a tool in the diagnosis of silvery hair syndrome.

BACKGROUND/OBJECTIVES: Silvery hair syndrome is a rare, autosomal-recessive entity characterized by silvery gray hair, eyebrows, and eyelashes and may be associated or not with immunologic or neurologic alterations. Two main types have been recognized: Chediak-Higashi syndrome and Griscelli syndrome. Hair shaft examination under light microscopy has been a useful tool to differentiate Chediak-Higashi syndrome from Griscelli syndrome, although distribution of melanin varies according to hair color related to ethnicity. The objective was to compare the pattern of melanin in the skin and with the pattern of melanin distribution in the hair shaft. METHODS: Sixteen patients with silvery hair syndrome were selected (Chediak-Higashi syndrome 5, Griscelli syndrome 11). The distribution of melanin granules in skin and hair shafts was compared and correlated with clinical diagnoses. RESULTS: Chediak-Higashi syndrome was characterized by small granules of melanin uniformly distributed throughout the thickness of the epidermis. Griscelli syndrome was characterized by an irregular pigment distribution in the epidermal basal layer with large and dense granules alternating with areas lacking melanin pigment. In two cases, study of the hair was not conclusive, but the skin showed the characteristic pattern of Griscelli syndrome. CONCLUSION: Skin biopsy is a useful tool in differentiating Chediak-Higashi syndrome from Griscelli syndrome and as a complementary study in cases in which hair shaft pigment distribution does not support the diagnosis, especially in patients with fair hair. The distribution of melanin granules in the skin correlates with that observed in the hair shaft, allowing Chediak-Higashi syndrome to be differentiated from Griscelli syndrome, at any age.

Hepatorenal Tyrosinemia in Mexico: A Call to Action.

Hepatorenal tyrosinemia is a treatable metabolic disease characterized by progressive liver failure, renal damage and pronounced coagulopathy. Its clinical diagnosis is difficult because of its low prevalence and heterogeneous symptoms. In developed countries, expanded newborn screening, based on succinylacetone quantification by tandem mass spectrometry, has been very valuable in the early detection of hepatorenal tyrosinemia, providing the opportunity for rapid treatment of affected patients. In developing countries without systematic expanded newborn screening, however, diagnosis and treatment of this disease remain major challenges, as genetic diseases in these countries are not a health priority and there are few referral centers for infants with inherited errors of metabolism. This chapter describes the diagnosis, follow-up and outcome of 20 Mexican patients with hepatorenal tyrosinemia. This chapter also constitutes a call to action to pediatricians, gastroenterologists, geneticists and other health professionals, and to academic organizations, health authorities and patient advocacy groups, to promote early patient detection and treatment, reducing the unacceptably high mortality rate (75%) in Mexican infants with this potentially deadly but eminently treatable condition.

Video-assisted thoracoscopy for diaphragmatic plication: experimental study in a canine model.

BACKGROUND: Plication of a nonfunctional hemidiaphragm usually restores altered ventilatory mechanics. This study compared two techniques in performing diaphragmatic plication: video-assisted thoracoscopy (group A) and thoracotomy (group B). MATERIALS AND METHODS: Twenty dogs with induced paralysis of the right hemidiaphragm were randomly assigned to one of the two groups. Evaluations were performed before and after plication of the respiratory frequency (f) and lung area (LA) of the affected side. Operative time, time to resumption of walking, ingestion of fluids and solid food, pain intensity, and postoperative complications were measured. RESULTS: Group A had less pain after the surgery (P < 0.0001), earlier fluid ingestion (P < 0.05), and earlier resumption of walking (P < 0.019). Four weeks after the procedure, LA was similar in both groups, while a significant decrease in f was recorded in group A (P < 0.02). The remaining evaluated variables showed no differences. CONCLUSION: Both approaches were effective. Pain recorded in the postoperative period was less and recovery was faster in group A. Complications and surgical times were similar. The video-assisted thoracoscopy is a safe and efficient option for performing diaphragmatic plication in dogs.

[Clinicopathologic cases]. / Los casos clínicopatológicos.

The clinicopathologic conference (CPC) was introduced by Dr. Richard C. Cabot at the Massachusetts General Hospital in the U.S. early in the past century. In a short time, it became one of the most popular medical teaching tools in the world. Despite certain differences between beside diagnosis and CPC diagnosis, the latter is a valuable teaching exercise. During the past few decades, interest in CPCs has declined due to several issues: excessive concern with anatomic diagnosis at the expense of molecular pathogenesis and pathophysiology; emphasis on uncommon diseases; the pathologist being considered an adversary who enjoys demonstrating clinical discussion errors; autopsies failing to reveal abnormalities in physiopathologic disorders and it is not rare to fail to reveal cause of death, and the fact that very few cases are true diagnostic problems, due to advances in diagnostic techniques. In addition, with the decline of interest in autopsies during the past years, in several CPCs, many final diagnosis is performed by biopsy, laboratory tests, or imaging studies. The ideal CPC case to conserve the educational role of this exercise is an autopsy case with adequated clinical, laboratory and/or imaging studies.

Intestinal/Peritoneal tuberculosis in children: an analysis of autopsy cases.

Infection by Mycobacterium bovis is not infrequently identified in Mexico. Its relation to nonpasteurized milk products ingestion is well recognized with primary infection usually in the intestinal tract. The term "abdominal tuberculosis" includes peritoneal as well as primary and secondary intestinal tuberculosis. The clinical differentiation of these conditions is difficult. In this work, we reviewed the clinical and pathological features of 24 cases of children dying with tuberculosis in whom autopsy revealed abdominal disease in a referral hospital in Mexico City. We identified 8 cases of primary intestinal tuberculosis, with documentation of M. bovis in 6 of them, and 9 cases of secondary intestinal tuberculosis (primary pulmonary disease), all negative to M. bovis. Seven patients had peritoneal tuberculosis without intestinal lesions and with active pulmonary disease in 4 of them, and of the remaining three, two had mesenteric lymph node involvement suggesting healed intestinal disease. In this approach to abdominal tuberculosis, postmortem analysis was able to differentiate primary from secondary intestinal tuberculosis and to define the nature of peritoneal involvement. This discrimination gives rise to different diagnostic approaches and epidemiological and preventive actions, particularly in countries where tuberculosis is endemic and infection by M. bovis continues to be identified.

Portopulmonary hypertension in children. A study in pediatric autopsies.

BACKGROUND AND AIMS: The relative frequency and risk factors of portopulmonary hypertension in children have not been defined with precision. The few published reports refer to isolated cases or small series from selected populations. The development of pulmonary hypertension in patients with portal hypertension is seldom suspected or documented during life. The examination of autopsy material can identify these cases because pulmonary hypertension produces characteristic histological changes in the pulmonary vasculature. METHODS: Autopsy cases with evidence of portal hypertension were retrieved. Slides of pulmonary tissue from these cases were examined in search of histopathological changes of hypertensive arteriopathy RESULTS: Seventy six cases of portal hypertension were identified among 7060 autopsies collected between January 1971 and January 2008 (1.07%). Four cases with histopathological evidence of pulmonary hypertension were identified. This represents 5.2% of all cases with portal hypertension. These four patients were females in late childhood or adolescence with idiopathic portal hypertension. Pulmonary hypertension was not diagnosed during their lifetime. CONCLUSIONS: Idiopathic portal hypertension in adolescent girls should be considered a risk factor for the development of portopulmonary hypertension, very likely as a consequence of the functional preservation of hepatic tissue that allows a prolonged survival. An oriented search for early signs of pulmonary hypertension in these patients would appear advisable in order to install timely treatment.

Exogenous lipoid pneumonia superinfected with acid-fast bacilli in infants: a report of nine cases.

Super-infection of an exogenous lipoid pneumonia by nontuberculous mycobacteria has been described in the literature. It produces a distinctive histologic picture with suppurative, noncaseating granulomas surrounding lipid vacuoles containing acid-fast bacilli. Mainly isolated cases have been found, but seldom in children. We describe a series of 9 children with similar histological findings. All our patients were under 1 year of age, malnourished, and with chronic respiratory symptoms. The diagnosis, based on the characteristic histology with acid-fast rods, was established at autopsy in 4 cases, on lobectomy specimens in 4 and by open lung biopsy in 1. Mycobacterium fortuitum-chelonei was cultured in 1 case. Gastro-esophageal reflux was documented in all 4 cases in which it was explored. Aspiration of lipid gastric contents or of oil given as medication can result in exogenous lipoid pneumonia, which in turn becomes super-infected with mycobacteria. Recognition of the distinctive histology permits the diagnosis of this complication.

Las sesiones anatomoclinicas en Mexico en los albores del siglo XXI / Postmortem clinical anatomy sessions in Mexico at the dawn of the 21st. century

The authors present a defense of postmortem clinical anatomy sessions, which contributed enormously to the development of clinical medicine but which today draw little interest in medical studies. Nevertheless, the sessions still provide an unrivalled exercise in diagnosis for medical students and an excellent method of continuing education for practicing professionals. Autopsies make it possible to confirm or correct clinical diagnoses, including those obtained through highly complex technological procedures; they contribute to the discovery of new diseases and other abnormalities; they promote research; they provide reliable statistics on morbidity and mortality; they produce useful genetic information; they facilitate interdisciplinary discussion and knowledge exchange; and they can serve as an indicator of the quality of medical care. The authors recommend reviving the high academic standards of postmortem clinical anatomy sessions and urge professionals in health institutions to contribute as much as possible to the continuation and improvement of these sessions

Papel de la biopsia hepática en el diagnóstico de la colestasis prolongada en lactantes / Liver biopsy in the diagnosis of prolonged cholestasis in infants

Se presentan los resultados de una investigación retrospectiva que tiene como objetivo evaluar la eficacia del análisis histopatológico del hígado obtenido por biopsia percutánea para el diagnóstico diferencial de la colestasis prolongada en lactantes. Para tal efecto se comparan las características clínicas, las cifras de bilirrubinas en suero, los estudios de gamagrafía hepática y el resultado de la biopsia entre dos grupos de pacientes. Un grupo está constituído por 56 pacientes con obstrucción biliar extrahepática (atresia de vías biliares: 42; quiste de colédoco: 9; obstrucción extrínseca: 4; y enfermedad de Caroli: 1). El otro grupo de 54 niños tiene colestasis intrahepática con vías biliares permeables (hepatitis: 38; colestasis inespecífica: 14; y cirrosis: 2). Se concluye que la biopsia hepática por punción es el procedimiento más útil para el diagnóstico diferencial entre hepatitis y atresia, y se sugiere que este recurso diagnóstico debe practicarse en pacientes con colestasis prolongada cuando otros estudios no invasivos no hayan descartado un problema obstructivo, y antes de decidir la laparotomía exploradora.

Hipertensión porta en el niños: correlación clínico-patológica / Portal hypertension in children: clinico-pathologic correlation

Se analizan los sintomas predominantes en 80 niños con hipertensión porta, 37 femininos y 43 masculinos, con edades comprendidas de 8 meses a 17 años; se mencionan las causas más frecuentes que incluyeron la trombosis de la vena porta, la cirrosis, la degeneración cavernomatosa de la vena porta y la fibrosis hepática congenética, entre otras. Se hace un análisis estadístico con respecto a la sintomatologia de estos niños, según el tipo de obstrucción que presentaron

Encefalitis viral: revisión de 83 casos postmortem / Viral encephalitis: review of 83 cases postmortem

Se analizan algunas características anatomoclínicas de 83 casos de encefalitis viral diagnosticados en autopsias pediátricas. La frecuencia global de esta patología es del 2.13% de los estudios postmortem y en la mitad de los casos responsables de la muerte. La causa más frecuente en prescolares y escolares es la rabia, mientras que en niños más pequeños, la etiología predominante es el sarampión, el herpes y el citomegalovirus. Un grupo importante por su frecuencia e interés epidemiológico es la encefalitis viral de etiología no determinada. Este grupo constituye el 20% de esta serie y la falta de identificación etiológica se debe en parte a la poca utilización de los recursos diagnósticos tanto serológico como de cultivo

Hipertensión porta en el niño: diagramas de flujo para su diagnóstico / Portal hypertension in the child: flow diagrams to its diagnosis

Se revisan los signos y síntomas que se observan en los niños que cursan con elevación de la presión del sistema venoso porta. Se propone una forma de estudio sistematizado, para el análisis de los mismos, mediante los cuales se pueda llegar al diagnóstico del sitio de la obstrucción y de la causa que originó el problema

Las causas de muerte por hipotiroidismo congénito: un estudio realizado en necropsias / Causes of death in congenital hypothyroidism: a postmortem study

Los niños con hipotiroidismo congénito se hallan en riesgo de fallecer en forma inesperada. Con el propósito de probar esta hipótesis, se estudiaron las causas de muerte y las enfermedades concomitantes en 16 necropsias de casos con hipotiroidismo congénito. Cuatro pacientes con atireosis fallecieron sin diagnóstico ni tratamiento. El resto fueron diagnosticados tardíamente(después de los dos meses de edad), por exhibir niveles bajos de T3 y T4. Nueve casos de la serie fallecieron inesperadamente, tres en el hospital y seis en su domicilio. Los hallazgos de la necropsia sugieren broncoaspiración en cinco casos y falla cardíaca en cuatro. Los siete casos restantes fallecieron por complicaciones de índole infecciosa. Se concluye que en el hipotiroidismo congénito diagnosticado y tratado tardíamente, existen trastornos orgánicos sistémicos, que asociados al daño neurológico pueden provocar la muerte. Una atención particular a la función cardíaca y a los trastornos en la deglución, podrían detectar los casos de alto riesgo

Anomalía de Ebstein / Ebstein's anomaly

La anomalía de Ebstein, descrita por primera vez en 1866, es una malformación congénita poco frecuente. Se caracteriza morfológicamente por la implantación baja de la válvula tricúspide, principalmente de la valva posterior, con adosamiento de las tres a la pared del ventrículo derecho, que se encuentra reducido y con su porción superior auriculizada. Es una cardiopatía que puede ser tolerable, aun sin tratamiento, dependiendo de la gravedad de la malformación, de la capacidad funcional de las valvas, y de la presencia de anomalías concomitantes. Se asocia frecuentemente a foramen oval amplio, conducto arterioso permeable, y estenosis o atresia pulmonar. Se han descrito casos asociados a síndrome de Down, Marfán y Noonan, entre otros. En nuestra serie de 4,320 autopsias (1970-1986), hubo 654 cardiopatías congénitas, de las cuales seis fueron diagnosticadas como Ebstein (0.9%), aproximándose de esta forma a las estadísticas informadas por numerosos autores. Las edades variaron entre 7 y 120 días; no hubo diferencias por sexo. En todos los casos, esta anomalía se asoció a foramen oval amplio y conducto arterioso permeable; en dos casos a estenosis valvular e hipoplasia de la pulmonar y en dos con atresia valvular pulmonar. En dos pacientes se identificaron anomalías extracardiacas. Tres casos fueron diagnosticados en vida con estudios especiales de cateterismo y estudio fonomecanocardiográfico