Alzheimer’s Disease among American Minority Populations: An Ecological Exploratory Study

A significant public health concern with regards to increasing rates of Alzheimer’s is that it disproportionately affects minority groups in the United States. The present ecological exploratory study uses secondary aggregate data from the fifty United States in the year of 2019. The purpose of this study was to address the disparities in Alzheimer’s in minority populations in the US and explore associated factors. The “minority” populations considered were African American and Hispanic populations, and the “majority” population was referred to as “white”. The data were extracted from the United States Census Bureau, the CDC National Center for Health Statistics, and the Behavioral Risk Factor Surveillance System (BRFSS) Dataset. The prevalence rates of Alzheimer’s disease are greatest in both older Hispanic (12.2%) and African Americans (13.8%), compared to older whites (10.3%) in the investigated time period. Our results showed that being over 65 years old (p=.009), with a below-average ($62,843) median household income (p=.024), history of stroke (p=.029), and being a part of the Hispanic population (p=.036), were significantly associated with Alzheimer’s mortality rates in the United States. By identifying disparities in access to Alzheimer’s healthcare and at-risk communities, more comprehensive intervention strategies can be developed to promote change and advocate for more Alzheimer’s education and resource allocation for minority populations

A human organoid model of aggressive hepatoblastoma for disease modeling and drug testing

Hepatoblastoma is the most common childhood liver cancer. Although survival has improved significantly over the past few decades, there remains a group of children with aggressive disease who do not respond to current treatment regimens. There is a critical need for novel models to study aggressive hepatoblastoma as research to find new treatments is hampered by the small number of laboratory models of the disease. Organoids have emerged as robust models for many diseases, including cancer. We have generated and characterized a novel organoid model of aggressive hepatoblastoma directly from freshly resected patient tumors as a proof of concept for this approach. Hepatoblastoma tumor organoids recapitulate the key elements of patient tumors, including tumor architecture, mutational profile, gene expression patterns, and features of Wnt/β-catenin signaling that are hallmarks of hepatoblastoma pathophysiology. Tumor organoids were successfully used alongside non-tumor liver organoids from the same patient to perform a drug screen using twelve candidate compounds. One drug, JQ1, demonstrated increased destruction of liver organoids from hepatoblastoma tumor tissue relative to organoids from the adjacent non-tumor liver. Our findings suggest that hepatoblastoma organoids could be used for a variety of applications and have the potential to improve treatment options for the subset of hepatoblastoma patients who do not respond to existing treatments

Resistance of stem-like cells from neuroblastoma cell lines to commonly used chemotherapeutic agents

Background Cancer stem cell theory suggests that the presence of tumor initiating stem-like cells in cancers may be responsible for cancer progression and relapse. CD133 cell surface maker expression has been used to identify stem-like cells in cancer cell lines. Our goal was to identify such cells in neuroblastoma cell lines and to study the cytotoxicity of common anticancer drugs for those cells. Materials and Methods CD133+ cells from SK-N-SH and SK-N-BE cell lines were isolated using magnetic microbeads. Cytotoxicity of four anticancer drugs was studied on CD133+ and CD133− populations. The percentage of live, apoptotic, and dead cells in each population after drug treatment was estimated by MTT and PI/Annexin-binding assays. Western blot analyses were used to identify differences in the expression of kinases. Results Eight to 10% of SK-N-SH and 3–5% of SK-N-BE cells were CD133+. These cells were more resistant than CD133− cells to all four chemotherapeutic agents tested in the MTT assay. Decreased apoptosis was observed in CD133+ cells compared to CD133− cells by PI/Annexin V-binding assay. Western blot analysis showed that CD133+ cells expressed less MKP-1. Phosphorylated forms of both ERK and P-38 kinases were expressed at higher levels in CD133+ cells than in CD133− cells. Conclusions This study suggests that CD133+ cells are more resistant to anticancer drugs than CD133− cells. Differences in the expression and phosphorylation of kinases could be partially responsible for this difference. Targeting CD133-expressing cells could be a strategy to develop more effective treatments for neuroblastoma. Pediatr Blood Cancer 2010;54:361–368. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64907/1/22351_ftp.pd

Differentiated thyroid carcinoma in children and adolescents

From 1936 to 1990, 89 children and adolescents (72 girls and 17 boys) were treated for differentiated thyroid carcinoma at the University of Michigan Medical Center; 58 of these patients were first reported in 1971. Thirty (34%) patients had previously received external irradiation to the head and neck, although only 1 (3%) patient of the last 33 patients seen had this history. Patients first presenting from 1971 to 1990 had less advanced disease than those seen earlier. Also, during this time period, the rate of initial palpable cervical adenopathy fell from 63% to 36%, local infiltration of primary cancer from 31% to 6%, and initial pulmonary metastases from 19% to 6%. The incidence of cervical nodal metastases has remained 88% for 54 years. Papillary or the follicular variant of papillary carcinoma was found in 93% of all patients. Seventy-nine (89%) patients had total or completion total thyroidectomy. Surgical management of lymphatic metastases varied from regional excision of nodes to radical neck dissection. The overall rate of permanent accidental recurrent laryngeal nerve palsy and hypoparathyroidism was 4.5%, although neither has occurred in a child or adolescent undergoing surgery at the center in the past 25 years. The most recent 33 patients had a low rate of local/regional persistence or recurrence. Cervical nodal persistence occurred in 21%; there were no thyroid recurrences. Eighty-two percent of patients received 131 I. The long-term mortality rate was 2.2%. We continue to advocate total thyroidectomy, cervical lymph node dissection, and postoperative 131 I therapy as the most conservative treatment regimen for children with differentiated thyroid carcinoma. Entre 1936 et 1990, 89 enfants et adolescents (72 filles et 17 garons) ont été traités pour cancer différencie de la thyroïde au Centre Médical de l'Université de Michigan. Cinquante huit d'entre eux ont fait l'objet d'une publication en 1971. Trente de ces patients (34%) avaient eu une radiothérapie externe au niveau de la tête et/ou du cou, mais ce facteur n'a été retrouvé que chez un des 33 derniers patients (3%). Les patients vus entre 1971 et 1990 avaient une maladie moins avancée. Pendant cette période, le taux d'adénopathies cervicales palpables est passée de 63 à 36%; le pourcentage de patients ayant une infiltration locale, de 31 à 6%, et celui de métastases pulmonaires de 19 à 6%. L'incidence des métastases ganglionnaires cervicales, par contre, est restée de 88% depuis 54 ans. Le cancer était papillaire ou folliculaire dans 93% des cas. Soixante-neuf patients (89%) ont eu une thyroïdectomie totale, soit d'embl%ee soit secondairement. La thérapeutique des métastases ganglionnaires a varié depuis l'exérèse régionale et le curage ganglionnaire cervical. Le taux global de paralysie récurrentielle et de l'hypoparathyroïde était de 4.5%, mais aucune de ces deux complications n'a été observée pour les enfants opérés dans notre centre au cours des 25 dernières années. Parmi les 33 derniers patients, le taux de tissu résiduel ou de récidive était bas. Dans 21% des cas, il persistait du tissu néoplasique après chirurgie, sans récidive. Quatre-vingt pour cent de ces patients ont eu un traitement par l'iode 131. La mortalité à distance était de 2.2%. Nous continuous de recommander une thyroïdectomie totale, une lymphadénectomie cervicale et une iodothérapie post-opératoire par l'iode 131 comme le traitement les plus conservateurs du cancer différencié de la thyroïde chez l'enfant. Ochenta y nueve niños y adolescentes (72 de sexo femenino y 17 de sexo masculino) fuiron tratados por carcinoma tiroideo diferenciado en el Centro Médico de la Universidad de Michigan; 58 de estos pacientes fueron reportados por primera vez en 1971. Treinta pacientes (34%) tenían historia de irradiación a la cabeza y el cuello; sin embargo, solamente uno de los últimos 33 (3%) presentó tal historia. Los pacientes vistos entre 1971 y 1990 exhibían enfermedad menos avanzada que aquellos vistos previamente. Así mismo, la incidencia de adenopatías cervicales palpables descendió de 63% a 36%, la de infiltración local por cáncer primario de 31% a 6% y la de metástasis pulmonares iniciales de 19% a 6%. La incidencia de metástasis ganglionares cervicales se ha mantenido en 88% por 54 años. La variante papilar o folicular del carcinoma papilar se encontró en 93% de los pacientes de la serie. Setenta y nueve pacientes (89%) fueron sometidos a toroidectomía total o a reoperación para completar la tiroidectomía total. El manejo quirúrgico de las metástasis linfáticas varió desde la resección regional de los ganglios hasta la disección radical del cuello. La tasa global de lesión accidental, permanente o temporal, del nervio recurrente laríngeo y de hopoparatiroidismo fue 4.5%, aunque ninguna de estas complicaciones ha ocurrido en un niño o en un adolescente sometido a cirugía en nuestro centro médico en los últimos 25 años. Los últimos 33 pacientes exhibieron una tasa reducida de persistencia o de recurrencia local/regional. La persistencia ganglionar cervical se presentó en 21% de los casos; no hubo recurrencias tiroideas. Ochenta y dos por ciento de los pacientes recibió 131 I. La tassa de mortalidad a largo plazo fui 2.2%. Nuestro grupo continúa preconizando tiroidectomía total, disección ganglionar cervical y terapia postoperatoria con 131 I como la modalidad terapéutica más conservadora en carcinoma diferenciado de la glándula tiroidea en la niñez.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41290/1/268_2005_Article_BF02067317.pd

Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study

BackgroundTo better characterize short- term and long- term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD).MethodsPatients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long- term pancreatic function, recurrence, and survival) were collected.ResultsSixty- five patients from 18 institutions with a median age of 13 years (4 months- 22 years) and a median (IQR) follow- up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30- day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non- SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival.ConclusionThis is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156233/2/pbc28425.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156233/1/pbc28425_am.pd

Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study

Background: To better characterize short-term and long-term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD). Methods: Patients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long-term pancreatic function, recurrence, and survival) were collected. Results: Sixty-five patients from 18 institutions with a median age of 13 years (4 months-22 years) and a median (IQR) follow-up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30-day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non-SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival. Conclusion: This is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology

New insights into perinatal testicular torsion

Perinatal testicular torsion is a relatively rare event that remains unrecognized in many patients or is suspected and treated accordingly only after an avoidable loss of time. The authors report their own experience with several patients, some of them quite atypical but instructive. Missed bilateral torsion is an issue, as are partial torsion, possible antenatal signs, and late presentation. These data are discussed together with the existing literature and may help shed new light on the natural course of testicular torsion and its treatment. The most important conclusion is that a much higher index of suspicion based on clinical findings is needed for timely detection of perinatal torsion. It is the authors’ opinion that immediate surgery is mandatory not only in suspected bilateral torsions but also in cases of possible unilateral torsions. There is no place for a more fatalistic “wait-and-see” approach. Whenever possible, even necrotic testes should not be removed during surgery because some endocrine function may be retained

Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma

Background: Neuroblastoma (NB) tumours have the highest incidence of spontaneous remission, especially among the stage 4s NB subgroup affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical for therapeutic decisions. The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups. Methods: Thirty-five NB tumours from patients diagnosed at < 18 months (25 stage 4 and 10 stage 4s), were evaluated by allelic and gene expression analyses. Results: All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36), 23% 11q and/or 14q LOH (27%) and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 < 12 months tumours revealed distinct gene expression profiles. A significant portion of genes mapped to chromosome 1 (P < 0.0001), 90% with higher expression in stage 4s, and chromosome 11 (P = 0.0054), 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 < 18m, yet, association with chromosomes 1 (P < 0.0001) and 11 (P = 0.005) was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 < 18 months without MYCN amplification. Conclusion: Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour