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1.
Int J Rheum Dis ; 27(1): e14878, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37592395

ABSTRACT

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) is a rare chronic inflammatory disease that develops in adults. We present a case of SAPHO syndrome in a 37-year-old male presenting with gradually worsening back and neck pain for a 7-year period. The episodes were preceded by a history of pustular skin eruptions, which first appeared on the upper trunk and then involved his face and were pustular and scarring. The purpose of presenting this case report from Iraq is to raise awareness about this rare condition, which is frequently misdiagnosed and under-recognized.


Subject(s)
Acne Vulgaris , Acquired Hyperostosis Syndrome , Osteitis , Synovitis , Male , Adult , Humans , Acquired Hyperostosis Syndrome/complications , Acquired Hyperostosis Syndrome/diagnosis , Acquired Hyperostosis Syndrome/drug therapy , Synovitis/diagnosis , Back Pain/diagnosis , Back Pain/etiology , Skin , Acne Vulgaris/diagnosis
2.
Article in English | MEDLINE | ID: mdl-38071615

ABSTRACT

BACKGROUND: Many older adults with cancer have ≥2 impairments on geriatric assessment which impacts present and future frailty status, treatment tolerability, and outcomes. Our objective was to identify and describe distinct geriatric assessment impairment classes using latent class analysis (LCA) in older patients with gastrointestinal malignancies and assess 1-year mortality. METHODS: We used the Cancer & Aging Resilience Evaluation (CARE) Study, a registry of older adults (≥60 years) at University of Alabama at Birmingham. The analytic cohort included patients with gastrointestinal malignancies who completed a self-administered geriatric assessment (CARE tool) before chemotherapy and had ≥1 geriatric assessment impairment. Thirteen geriatric assessment impairments were used as indicators in LCA. Resultant classes were described, mortality was estimated, and risk contrasts (differences, hazard ratios) were calculated with 95% confidence intervals. For comparison, estimates were provided for frailty categories (robust, pre-frail, frail) determined from 44 items in the CARE tool. Stratified analyses included high-risk (pancreatic, hepatobiliary, esophageal) vs. low-risk gastrointestinal cancers, and stage (IV vs. I-III). RESULTS: Six geriatric assessment impairment classes were identified: Mild impairment (LC1); Social support impairment (LC2); Weight loss alone (LC3); Impaired, low anxiety/depression (LC4); Impaired with anxiety/depression (LC5); Global impairment (LC6). One-year mortality was 14%, 22%, 29%, 34%, 50% and 50% for LC1-LC6, respectively. For frailty categories, estimates ranged from 18% (robust) to 40% (frail). In stratified analyses, LC4-LC6 consistently had higher mortality estimates compared to LC1. CONCLUSIONS: The 6 geriatric assessment impairment classes showed a wider spread of mortality estimates compared to frailty categories and could be used to identify vulnerable patients and to plan interventions.

3.
eNeurologicalSci ; 33: 100486, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38053652

ABSTRACT

Background: Dandy-Walker malformation or syndrome is the most common posterior fossa malformation. It is commonly associated with other congenital anomalies such as cardiac defects; however, association with a giant occipital meningocele is extremely rare, as only around 34 cases have been described. Case description: We report a case of a 2-month-old female infant who presented with a midline, gigantic mass in the back of the head. It was first discovered on a prenatal ultrasound. The mass measured about 15 × 5 cm, extending to the midback, not changing in size with crying, not attached to the back, and with a positive transillumination test. The diagnosis was confirmed after doing a brain computed tomography, which revealed hypoplasia of the vermis with an enlarged posterior fossa as well as cystic dilation of both ventricles with herniation through a bone defect. Conclusion: Our case highlights a rare association between giant occipital meningocele and Dandy-Walker syndrome that is rarely discussed or reported in the medical literature. By reporting this extremely rare case of Dandy-Walker syndrome associated with a giant occipital meningocele, we hope to contribute to the creation of a database for future research so that a management protocol can be established for use by clinicians and neurosurgeons for better management of the condition.

4.
J Geriatr Oncol ; 14(8): 101644, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37806291

ABSTRACT

INTRODUCTION: Although geriatric assessments (GAs) are recommended for use in older adults with cancer, their integration into oncology practice remain suboptimal. Here, we report our experience integrating web-enabled GA (WeCARE) into oncology practice as an augmented delivery method and provider interface format to overcome implementation barriers. MATERIALS AND METHODS: Older patients (≥60 years) with a gastro-intestinal (GI) malignancy presenting for an initial visit to medical oncology clinic at a single institution between December 7, 2021 and October 10, 2022 were contacted by staff two days in advance of their visits and sent a link to the WeCARE GA, rather than the paper version used previously. Results were directly embedded into the medical record. We describe our initial implementation outcomes and the results of a provider usability survey. RESULTS: Of 266 eligible patients, 221 (83.1%) were successfully contacted by telephone and 200 (75.2%) completed the WeCARE prior to their appointment. More than one phone call was required to make contact for 35.7% of patients, with a mean duration of phone conversation of 2.8 min. Most patients preferred email delivery to text (63% vs 31%); 4.5% were unable to access surveys due to inadequate technology, and 25.7% brought up additional logistical concerns. Among GI oncology providers surveyed, all six found the WeCARE tool and dashboard acceptable, appropriate, and feasible. However, only a third of providers often or always used the dashboard to inform treatment decisions and guide interventions. DISCUSSION: With nearly three-quarters of patients completing the WeCARE prior to their visits with minimal staff support and time required, this method of administration may be a viable format to overcome barriers to GA implementation. Additional work is needed to integrate the results meaningfully into clinical practice.


Subject(s)
Neoplasms , Outpatients , Humans , Aged , Neoplasms/therapy , Medical Oncology , Geriatric Assessment , Aging
6.
Clin Case Rep ; 11(6): e7559, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37323252

ABSTRACT

Key Clinical Message: Azathioprine, used for vasculitis and connective tissue diseases, carries long-term cancer risks. This case report raises awareness among healthcare providers about such risks and emphasizes the need for taking necessary precautions to avoid them while treating such diseases. Abstract: We present an Azathioprine-induced lymphoma case in a 51-year-old male patient with Takayasu arteritis who presented with painless cervical swelling, itching, weight loss, and decreased appetite. This case report aims to increase awareness of the potential long-term cancer risks associated with azathioprine use in the treatment of chronic diseases.

7.
Cancer Med ; 12(12): 13846-13855, 2023 06.
Article in English | MEDLINE | ID: mdl-37245226

ABSTRACT

BACKGROUND: Basic resource needs related to transportation, housing, food, and medications are important social determinants of health and modifiable indicators of poverty, but their role in modifying the risk of frailty and health-related quality of life (HRQoL) remains unknown. The goal of our study was to examine the prevalence of unmet basic needs and their association with frailty and HRQoL in a cohort of older adults with cancer. METHODS: The CARE registry prospectively enrolls older adults (≥60 years) with cancer. Assessments of transportation, housing, and material hardship were added to the CARE tool in 8/2020. The 44-item CARE Frailty Index was used to define frailty, and subdomains of physical and mental HRQoL were assessed using the PROMIS® 10-global. Multivariable analysis examined the association between unmet needs with frailty and HRQoL subdomains, adjusting for covariates. RESULTS: The cohort included 494 participants. Median age of 69 years, 63.6% were male and 20.2% were Non-Hispanic (NH) Black. Unmet basic needs were reported in 17.8% (transportation 11.5%, housing 2.8%, and material hardship 7.5%). Those with unmet needs were more often NH Black (33.0% vs. 17.8%, p = 0.006) and less educated (

Subject(s)
Frailty , Neoplasms , Humans , Male , Aged , Female , Quality of Life , Frailty/epidemiology , Neoplasms/epidemiology , Neoplasms/therapy , Ethnicity , Registries
8.
Dis Colon Rectum ; 66(9): 1245-1253, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37235857

ABSTRACT

BACKGROUND: Despite the known influences of both race- and aging-related factors in colorectal cancer outcomes and mortality, limited literature is available on the intersection between race and aging-related impairments. OBJECTIVE: To explore racial differences in frailty and geriatric deficit subdomains among patients with colorectal cancer. DESIGN: Retrospective study using data from the Cancer and Aging Resilience Evaluation registry. SETTINGS: A comprehensive cancer center in the Deep South. PATIENTS: Older adults (aged ≥60 years) with colorectal cancer. MAIN OUTCOME MEASURES: Measure of frailty and geriatric assessment subdomains of physical function, functional status, cognitive complaints, psychological function, and health-related quality of life. RESULTS: Black patients lived in areas with a higher social vulnerability index compared to White patients (0.69 vs 0.49; p < 0.01) and had limited social support more often (54.5% vs 34.9%; p = 0.01). After adjustment for age, cancer stage, comorbidities, and social vulnerability index, Black patients were found to have a higher rate of frailty than White patients (adjusted OR 3.77; 95% CI, 1.76-8.18; p = 0.01). In addition, Black patients had more physical limitations (walking 1 block: adjusted OR 1.93; 95% CI, 1.02-3.69; p = 0.04), functional limitations (activities of daily living: adjusted OR 3.21; 95% CI, 1.42-7.24; p = 0.01), and deficits in health-related quality of life (poor global self-reported health: adjusted OR 2.45; 95% CI, 1.23-5.13; p = 0.01). Similar findings were shown after stratification by stage I to III vs IV. LIMITATIONS: Retrospective study at a single institution. CONCLUSIONS: Among older patients with colorectal cancer, Black patients were more likely to be frail than White patients, with deficits observed specifically in physical function, functional status, and health-related quality of life. Geriatric assessment may provide an important tool in addressing racial inequities in colorectal cancer. DIFERENCIAS RACIALES EN LOS DFICITS RELACIONADOS CON EL ENVEJECIMIENTO ENTRE ADULTOS MAYORES CON CNCER COLORRECTAL: ANTECEDENTES: A pesar de las influencias conocidas de los factores relacionados con la raza y el envejecimiento en los resultados y la mortalidad del cáncer colorectal, hay muy poca literatura sobre la intersección entre los impedimentos relacionados con la raza y el envejecimiento.OBJETIVO: El objetivo era explorar las diferencias raciales en los subdominios de fragilidad y déficit geriátrico entre los pacientes con cáncer colorectal.DISEÑO: Estudio retrospectivo utilizando datos del registro Cancer and Aging Resilience Evaluation.AJUSTES: Un centro oncológico integral en el Sur Profundo.PACIENTES: Adultos mayores (≥60 años) con cáncer colorrectal de raza Negra o Blanca.PRINCIPALES MEDIDAS DE RESULTADO: Medida compuesta de fragilidad y subdominios de evaluación geriátrica de función física, estado funcional, quejas cognitivas, función psicológica y calidad de vida relacionada con la salud.RESULTADOS: De los 304 pacientes incluidos, el 21,7% (n = 66) eran negros y la edad media era de 69 años. Los pacientes negros vivían en áreas con un índice de vulnerabilidad social (SVI) más alto en comparación con los pacientes blancos (SVI 0,69 vs 0,49; p < 0,01) y con mayor frecuencia tenían apoyo social limitado (54,5% vs 34,9%; p = 0,01). Después de ajustar por edad, estadio del cáncer, comorbilidades y SVI, los pacientes de raza negra tenían una mayor tasa de fragilidad en comparación con los pacientes de raza blanca (ORa 3,77, IC del 95%: 1,76-8,18; p = 0,01). Además, los pacientes negros tenían más limitaciones físicas (caminar 1 cuadra: ORa 1,93, IC 95% 1,02-3,69; p = 0,04), limitaciones funcionales (actividades de la vida diaria: ORa 3,21, IC 95% 1,42-7,24; p = 0,01 ) y déficits en la calidad de vida relacionada con la salud (mala salud global autoinformada: ORa 2,45, IC 95% 1,23-5,13; p = 0,01). Las quejas cognitivas y las funciones psicológicas no difirieron según la raza (p > 0,05). Se mostraron hallazgos similares después de la estratificación por estadio I-III frente a IV.LIMITACIONES: Estudio retrospectivo en una sola institución.CONCLUSIONES: Entre los pacientes mayores con cáncer colorrectal, los pacientes negros tenían más probabilidades que los pacientes blancos de ser frágiles, observándose déficits específicamente en la función física, el estado funcional y la calidad de vida relacionada con la salud. La evaluación geriátrica puede proporcionar una herramienta importante para abordar las desigualdades raciales en el cáncer colorrectal.


Subject(s)
Colorectal Neoplasms , Frailty , Humans , Aged , Activities of Daily Living , Quality of Life , Race Factors , Retrospective Studies , Aging
9.
J Geriatr Oncol ; 14(4): 101505, 2023 05.
Article in English | MEDLINE | ID: mdl-37087962

ABSTRACT

INTRODUCTION: Rural-urban disparities persist in cancer mortality, despite improvement in cancer screening and treatment. Although older adults represent the majority of cancer cases and are over-represented in rural areas, few studies have explored rural-urban disparities in mortality and age-related impairments among older adults with cancer. MATERIALS AND METHODS: We included 962 newly-diagnosed older adults (≥60 years) with cancer who underwent geriatric assessment (GA) at their first pre-chemotherapy visit to an academic medical center in the Southeastern United States. We used Rural-Urban Commuting Area (RUCA) codes to classify residence at time of diagnosis into urban and rural areas. We used one-year survival and pre-treatment frailty as outcomes. We used Cox proportional hazards regression to evaluate the association between residence and one-year mortality, and logistic regression to evaluate the association between residence and pre-treatment frailty. All tests were two-sided. RESULTS: Median age at GA was 68.0 (interquartile rage [IQR]: 64.0, 74.0) years; most had colorectal cancer (24.3%) with advanced stage (III/IV 73.2%) disease. Overall, 11.4% resided in rural and 88.6% in urban areas. Rural areas had a higher proportion of White and less educated participants. After adjustment for age, sex, race, education, employment status, and cancer type/stage, rural residence was associated with higher hazard of one-year mortality (hazard ratio [HR] = 1.78, 95% confidence interval [CI] = 1.23, 2.57) compared to urban residence. Frailty was an effect modifier of this association (HROverall = 1.83, 95% CI = 1.27, 2.57; HRFrail = 2.05, 95% CI = 1.23, 3.41; HRNot Frail = 1.55, 95% CI = 0.90, 2.68). DISCUSSION: Among older adults with newly diagnosed cancer, rural residence was associated with reduced one-year survival, particularly among frail older adults. The rural-urban disparities observed in the current study may be due to frailty in conjunction with disparities in social determinants of health across rural and urban areas. Future studies should focus on understanding and intervening on underlying causes of these disparities.


Subject(s)
Frailty , Neoplasms , Humans , Aged , Geriatric Assessment , Frailty/diagnosis , Frailty/epidemiology , Rural Population , Registries , Aging
10.
Medicine (Baltimore) ; 102(14): e33456, 2023 Apr 07.
Article in English | MEDLINE | ID: mdl-37026903

ABSTRACT

RATIONALE: Pancreatic insulinomas are the most frequent pancreatic endocrine neoplasms. They are insulin-secreting pancreatic tumors that induce extreme, recurrent, and near-fatal hypoglycemia. Insulinomas affect 1 to 4 individuals in a million of the general population and account for about 1% to 2% of all pancreatic tumors. PATIENT CONCERNS: Recurrent episodes of sweating, tremor, weakness, confusion, palpitation, blurred vision, and fainting for 2 months and was misdiagnosed as having atrial fibrillation. DIAGNOSIS: He was misdiagnosed as having atrial fibrillation to highlight the importance of atrial fibrillation as unusual mimicker of insulinoma and to encourage clinicians about the importance of early and appropriate management in such cases. INTERVENTIONS: Endoscopic ultrasound for the pancreatic parenchyma was done, and it showed a hypoechoic homogenous mass located at the pancreatic head measuring 12 mm × 15 mm with no local vascular involvement, blue in elastography, hypervascular with Doppler study, and a normal pancreatic duct diameter. OUTCOMES: His condition was stable, and he was discharged home 2 days later. CONCLUSION: The diagnosis of insulinoma is usually difficult and late due to the extremely low incidence of the disease and the similarity of its clinical presentation to numerous other conditions, the most reported is epilepsy.


Subject(s)
Atrial Fibrillation , Insulinoma , Pancreatic Neoplasms , Male , Humans , Insulinoma/diagnostic imaging , Insulinoma/pathology , Atrial Fibrillation/diagnosis , Iraq , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Diagnostic Errors
11.
Clin Case Rep ; 11(3): e7120, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36941840

ABSTRACT

By reporting this case, we hope to encourage medical professionals to concentrate on diagnosing old patients with unusual presentation of rheumatoid arthritis.

12.
eNeurologicalSci ; 30: 100449, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36845277

ABSTRACT

Background: An encephalocele is a congenital neural tube defect that is estimated to have an incidence of 1-2 cases per 10,000 live births. There have been a few cases of double encephaloceles reported in the medical literature. We report an extremely rare case of double encephalocele with an atrial septal defect in Iraq. Case presentation: A 2-month-old female infant presented with two swellings at the back of her head since birth. Her mother received poor prenatal care. The examination revealed a microcephaly head and two sacs in the occipital region, which were not connected and were covered completely by skin. The surgery includes a transverse incision, excision of both sacs with necrotic tissue, a duroplasty, and a water-tight dural closure. The operation proceeded without any neurological sequelae or cerebrospinal fluid leakage. Conclusion: Double encephalocele is a congenital neural tube defect that is rarely discussed or reported in the medical literature. The management of this condition might be difficult because it requires a special approach for each patient. This case report from Iraq is used to raise awareness about this particular disorder and to motivate clinicians about the importance of early and appropriate management for such cases.

13.
Mar Pollut Bull ; 187: 114610, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36669300

ABSTRACT

This paper presents experimental measurements of beaching times for buoyant microplastic particles released, both in the pre-breaking region and within the surf zone. The beaching times are used to quantify cross-shore Lagrangian transport velocities of the microplastics. Prior to breaking the particles travel onshore with a velocity close to the Lagrangian fluid particle velocity, regardless of particle characteristics. In the surf zone the Lagrangian velocities of the microplastics increase and become closer to the wave celerity. Furthermore, it is demonstrated that particles having low Dean numbers (dimensionless fall velocity) are transported at higher mean velocities, as they have a larger tendency to be at the free-surface relative to particles with higher Dean numbers. An empirical relation is formulated for predicting the cross-shore Lagrangian transport velocities of buoyant microplastic particles, valid for both non-breaking and breaking irregular waves. The expression matches the present experiments well, in addition to two prior studies.


Subject(s)
Microplastics , Water Pollutants, Chemical , Plastics , Water Pollutants, Chemical/analysis , Environmental Monitoring
14.
J Am Geriatr Soc ; 71(1): 136-144, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36208421

ABSTRACT

BACKGROUND: Older adults with cancer are at increased risk of treatment-related toxicities and excess mortality. We evaluated whether a patient-reported geriatric assessment (GA) based frailty index can identify those at risk of adverse outcomes. METHODS: Older adults (≥60 years) enrolled in a single-institutional prospective registry underwent patient-reported GA at initial evaluation in our medical oncology clinic. Using deficit accumulation method, we constructed a 44-item frailty index (CARE-FI), categorizing patients as robust, pre-frail, and frail. The primary outcome was overall survival (OS). Secondary outcomes included (a) functional decline at 3 months post-therapy (b) incident grade ≥3 treatment-related toxicities at six-month post-treatment. We used multivariate Cox and logistic regression models respectively to study the impact of frailty on primary and secondary outcomes. RESULTS: We identified 589 older adults with a median age of 69 years; 55% males and 73% Whites. Overall, 168 (29%) were pre-frail and 230 (39%) frail. Being frail (vs. robust) was associated with worse OS (Hazards Ratio, HR 1.83, 95% Confidence Interval, CI 1.34-2.49, p < 0.001) after adjusting for age, sex, race/ethnicity, cancer type, cancer stage, and line of therapy. Similarly, frailty was associated with increased risk of functional decline (OR 3.01; 95% CI 1.33-6.81; p = 0.008) and grade ≥3 non-hematologic toxicities (OR 3.65; 95% CI 1.54-8.69; p = 0.003) but not hematologic toxicities (OR 1.01; 95% CI 0.46-2.22; p = 0.97). CONCLUSIONS: Our frailty index using a patient-reported GA is a robust predictor of survival, functional decline, and treatment related toxicity among older adults with GI malignancies.


Subject(s)
Frailty , Gastrointestinal Neoplasms , Male , Aged , Humans , Female , Frailty/epidemiology , Frail Elderly , Geriatric Assessment/methods , Patient Reported Outcome Measures
15.
Clin Case Rep ; 10(12): e6775, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36545557

ABSTRACT

This case report presents the first H-syndrome rarity in Iraq, a 12-year-old female patient who was attending the Rheumatology out clinic for progressive hands joint deformities. She has a history of a multi-systemic collection of diseases with various clinical features that include beta thalassemia minor, sensorineural deafness, and celiac disease.

16.
Support Care Cancer ; 30(12): 9793-9801, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36329186

ABSTRACT

PURPOSE: The impact of pain on functional status and mental health among older adults with cancer is a relevant, yet understudied. We sought to identify the prevalence of pain at diagnosis in older adults with gastrointestinal (GI) malignancies and evaluate the association of pain with functional status limitations, cognition, and mental health. METHODS: This prospective cross-sectional study included older adults (age ≥ 60) with GI cancers enrolled in the CARE Registry. Pain measured in numeric rating scale from 0 to 10. We utilized the literature based cutoff for moderate-severe as ≥ 4. Logistic regression used to assess differences in functional status, falls, cognitive complaints, and depression/anxiety associated with moderate/severe pain, adjusted for sex, race, education, ethnicity, marital status, cancer type/stage, and treatment phase. RESULTS: Our cohort included 714 older adults with an average mean age of 70 years and 59% male. Common diagnoses included colorectal (27.9%) and pancreatic (18%). A total of 43.3% reported moderate/severe pain. After multivariate adjusting for covariates, participants with self-reported moderate/severe pain were more likely to report limitations in instrumental activities of daily living (adjusted odds ratio [aOR] 4.3 95% confidence interval [CI] 3.1-6.1, p < .001), limitation in activities of daily living (aOR 3.2 95% CI 2.0-5.1, p < .001), cognitive complaints (aOR 2.9 95% CI 1.4-6.0, p < .004), anxiety (aOR 2.2 95% CI 1.4-3.4, p < 0.01), and depression (aOR 3.7 95% CI 2.2-6.5, p < .001). CONCLUSIONS: Pain is common among older adults with GI cancers and is associated with functional status limitations, cognitive complaints, and depression/anxiety. Strategies to reduce pain and minimize its potential impact on function and mental health warrant future research.


Subject(s)
Activities of Daily Living , Gastrointestinal Neoplasms , Humans , Male , Aged , Female , Activities of Daily Living/psychology , Cross-Sectional Studies , Prospective Studies , Aging , Pain/epidemiology , Pain/etiology , Gastrointestinal Neoplasms/complications , Gastrointestinal Neoplasms/epidemiology , Registries
17.
Front Immunol ; 13: 975233, 2022.
Article in English | MEDLINE | ID: mdl-36189285

ABSTRACT

Gene-modified cellular therapies carry inherent risks of severe and potentially fatal adverse events, including the expansion of alloreactive cells or malignant transformation due to insertional mutagenesis. Strategies to mitigate uncontrolled proliferation of gene-modified cells include co-transfection of a suicide gene, such as the inducible caspase 9 safety switch (ΔiC9). However, the activation of the ΔiC9 fails to completely eliminate all gene-modified cells. Therefore, we tested a two suicide gene system used independently or together, with the goal of complete cell elimination. The first approach combined the ΔiC9 with an inducible caspase 8, ΔiC8, which lacks the endogenous prodomain. The rationale was to use a second caspase with an alternative and complementary mechanism of action. Jurkat cells co-transduced to co-express the ΔiC8, activatable by a BB homodimerizer, and the ΔiC9 activatable by the rapamycin analog sirolimus were used in a model to estimate the degree of inducible cell elimination. We found that both agents could activate each caspase independently, with enhanced elimination with superior reduction in cell regrowth of gene-modified cells when both systems were activated simultaneously. A second approach was employed in parallel, combining the ΔiC9 with the RQR8 compact suicide gene. RQR8 incorporates a CD20 mimotope, targeted by the anti-CD20 monoclonal antibody rituxan, and the QBend10, a ΔCD34 selectable marker. Likewise, enhanced cell elimination with superior reduction in cell regrowth was observed when both systems were activated together. A dose-titration effect was also noted utilizing the BB homodimerizer, whereas sirolimus remained very potent at minimal concentrations. Further in vivo studies are needed to validate these novel combination systems, which may play a role in future cancer therapies or regenerative medicine.


Subject(s)
Genes, Transgenic, Suicide , Sirolimus , Caspase 8/genetics , Caspase 9/genetics , Caspase 9/metabolism , Genes, Transgenic, Suicide/genetics , Humans , Rituximab , Sirolimus/pharmacology
18.
JCO Clin Cancer Inform ; 6: e2200065, 2022 09.
Article in English | MEDLINE | ID: mdl-36070529

ABSTRACT

PURPOSE: Identifying older patients with GI malignancies who are at increased risk of mortality remains challenging. The goal of our study was to examine geriatric assessment (GA) predictors of 1-year mortality and explore the use of a survival tree analysis in a prospective cohort of older adults (≥ 60 years) with newly diagnosed GI malignancies. METHODS: Survival tree analysis was performed to understand variable interactions and identify predictors of overall survival, computed from time of GA to death or last follow-up. Cox regression was used to estimate associations of 1-year mortality, first using a base model (age, race, cancer stage, cancer risk group, and planned chemotherapy), then using all significant predictors from the univariable analyses, and finally only those identified in survival tree analysis. RESULTS: A total of 478 participants met eligibility, with a mean age of 70 years. The survival tree analysis identified nutrition, cancer stage, physical and emotional health, age, and functional status as predictors of mortality. Older patients without malnutrition or depression had the best 1-year survival, whereas those with malnutrition, stage IV disease, and functional limitations had the worst 1-year survival. Our base model demonstrated good discrimination (area under curve [AUC] 0.76) but was improved with the addition of GA variables (AUC 0.82) or from survival tree analysis (AUC 0.82). CONCLUSION: Measures of function, nutrition, and mental health are important predictors of mortality in older adults with GI cancers. Using GA as part of clinical management can aid in the prediction of survival and help inform treatment decision making.


Subject(s)
Malnutrition , Neoplasms , Aged , Geriatric Assessment , Humans , Neoplasms/drug therapy , Prospective Studies , Survival Analysis
19.
JCO Oncol Pract ; 18(11): e1796-e1806, 2022 11.
Article in English | MEDLINE | ID: mdl-36075013

ABSTRACT

PURPOSE: Frailty predicts poor outcomes in older adults with cancer, but how it differs between different cancer types is unknown. We examined differences in pretreatment frailty between colorectal (CRC), pancreatic, and hepatobiliary cancers. METHODS: We included older adults age 60 years or older with the above cancer types enrolled in the Cancer and Aging Resilience Evaluation registry. Frailty was defined using a 44-item Cancer and Aging Resilience Evaluation frailty index constructed on the basis of the principles of deficit accumulation (including several geriatric assessment impairments encompassing malnutrition, functional status, comorbidities, anxiety, depression, cognitive complaints, health-related quality of life, falls, ability to walk one block, interference in social activities, and polypharmacy). Multivariable logistic regression models were used to examine the adjusted odds ratio (aOR) of frailty between cancer types. RESULTS: A total of 505 patients were included (mean age 70 years, 59% male): 211 (41.8%) CRC, 178 (35.2%)pancreatic cancer, and 116 (23.0%) hepatobiliary cancer. Patients with pancreatic cancer had the highest prevalence of frailty (23.3% CRC, 40.6% pancreatic, 34.3% hepatobiliary; P = .001). Both pancreatic (aOR, 2.18; 95% CI, 1.38 to 3.45), and hepatobiliary cancer (aOR, 1.73; 95% CI, 1.03 to 2.93) were independently associated with higher odds of frailty relative to CRC. Frailty was driven by higher rates of malnutrition and instrumental activities of daily living impairments in patients with pancreatic cancer and higher number of comorbidities in patients with hepatobiliary cancer. CONCLUSION: Older adults with pancreatic and hepatobiliary cancers are at high-risk of pretreatment frailty. Early interventions to improve nutritional and functional status and optimization of comorbidities may help improve outcomes.


Subject(s)
Frailty , Gastrointestinal Neoplasms , Malnutrition , Pancreatic Neoplasms , Humans , Male , Aged , Middle Aged , Female , Frailty/complications , Frailty/epidemiology , Activities of Daily Living , Quality of Life , Gastrointestinal Neoplasms/complications , Gastrointestinal Neoplasms/epidemiology , Malnutrition/epidemiology , Aging , Registries , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/epidemiology
20.
J Cancer Surviv ; 2022 Sep 17.
Article in English | MEDLINE | ID: mdl-36114326

ABSTRACT

PURPOSE: Longitudinal change in patient-reported cognitive complaints (CC) in older adults with cancer is poorly understood. The purpose of this study was to evaluate early longitudinal CC and predictors among older adults with cancer. METHODS: We examined early CC change on the PROMIS® Short Form4a Cognitive Function among adults ≥ 60 years with GI cancer enrolled in the Cancer and Aging Resilience Evaluation (CARE) undergoing geriatric assessment (GA) at baseline and one 3-6-month follow-up. Multivariable linear regression examined associations of demographics, socioeconomics, GA domains, baseline cognitive score, and treatment toxicities on follow-up cognitive score. Bayesian analysis of covariance (ANCOVA) determined best fitting model. RESULTS: A total of 218 participants were included. The median follow-up was 3.7 months, the mean age was 69.2 ± 7.1, and 57.3% were male. The most common cancer was colorectal (30.7%) with most stage III/IV (73.7%). About half (51.8%) had stable cognition baseline to follow-up (follow-up t-score ± 5 points of baseline), 20.6% improved (≥ 5 increase), and 27.5% declined (≥ 5 decrease). After adjustment, there were no significant baseline predictors of follow-up cognitive t-score. Baseline t-score was the best-fitting predictor of follow-up t-score. CONCLUSIONS: In this first study, examining early change in CC among older adults with cancer, ~ 28% exhibited cognitive decline. Baseline cognition is the most important early predictor of follow-up cognition. Longer follow-up is needed to identify long-term predictors of CC change in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Cognitive decline, even early, may occur in many older adults with cancer. Baseline and regular follow-up assessments of cognitive symptoms are an important component of survivorship care.

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