Publications by authors named "Tahmineh Romero"

21 Publications

  • Page 1 of 1

Overwhelmed: a Dementia Caregiver Vital Sign.

J Gen Intern Med 2021 Aug 13. Epub 2021 Aug 13.

Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Background: The emotional stress of caring for someone with Alzheimer's disease and related dementias is high and results in adverse effects on caregivers and the persons living with disease. In preliminary work, caregiver reports of regularly feeling "completely overwhelmed" were associated with lack of measurable clinical benefit from a comprehensive dementia care program.

Objective: To examine the sociodemographic and clinical characteristics of all caregivers who felt overwhelmed at entry into a comprehensive dementia care program, the trajectory of this symptom over 1 year, and its predictive value for 1-year caregiver outcomes.

Design: Longitudinal cohort study SETTING: Academic health center PARTICIPANTS: Caregivers of patients enrolled in a comprehensive dementia care program EXPOSURES: Caregiver report of feeling "completely overwhelmed" at baseline MAIN MEASURES: Caregiver report of feeling "completely overwhelmed" at baseline and 1 year, and validated scales of caregiver strain, distress, depressive symptoms, burden, mortality, and long-term nursing home placement KEY RESULTS: Compared to caregivers who were not overwhelmed, overwhelmed caregivers had more distress from behavioral symptoms of the person living with dementia, worse depression scores, and higher composite dementia burden scores at baseline. They also had worse depressive symptoms, strain, and composite burden scores at 1 year, after adjustment for baseline scores. Having an overwhelmed caregiver did not predict long-term nursing home placement or mortality among persons with dementia.

Conclusions: A single question about whether a caregiver is overwhelmed might indicate caregivers who have considerable current and future symptom burden and who may benefit from increased support and resources.
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http://dx.doi.org/10.1007/s11606-021-07054-3DOI Listing
August 2021

Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features.

JAMA Netw Open 2021 Jul 1;4(7):e2115312. Epub 2021 Jul 1.

Department of Urology, Brady Urological Institute, Johns Hopkins University, Baltimore, Maryland.

Importance: The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown.

Objective: To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment.

Design, Setting, And Participants: This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020.

Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT).

Main Outcomes And Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression models.

Results: A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer-specific mortality; there was no difference in prostate cancer-specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer-specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P < .001).

Conclusions And Relevance: These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.15312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251338PMC
July 2021

Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer.

Eur Urol 2021 Aug 10;80(2):142-146. Epub 2021 May 10.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p < 0.001) and PCSM (p < 0.001). These data suggest that radiorecurrent HRPCa has an aggressive natural history and that DM is clinically evident early after BCR. These findings underscore the importance of further investigations into upfront risk assessment and prompt systemic evaluation upon recurrence in HRPCa. PATIENT SUMMARY: High-risk prostate cancer that recurs after radiation therapy is an aggressive disease entity and spreads to other parts of the body (metastases). Some 60% of metastases occur within 1 yr. Approximately 30% of these patients die from their prostate cancer.
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http://dx.doi.org/10.1016/j.eururo.2021.04.035DOI Listing
August 2021

Adverse Childhood Experiences and Association With Pediatric Asthma Severity in the 2016-2017 National Survey of Children's Health.

Acad Pediatr 2021 08 1;21(6):1025-1030. Epub 2021 May 1.

University of California Los Angeles, Department of Pediatrics, General Pediatrics (PG Szilagyi), Los Angeles, Calif.

Objectives: Prior studies have found that adverse childhood experiences (ACEs) are associated with asthma prevalence and onset, presumably related to stress and increased inflammation. We hypothesized that ACEs may be associated with asthma severity as well. We studied the 2016-2017 US National Survey of Children's Health dataset to explore the relationship between ACEs and pediatric asthma severity.

Methods: We analyzed children ages 0 to 17 years old who had current caregiver-reported asthma diagnosed by a healthcare provider. We reported descriptive characteristics using chi-square analysis of variance (ANOVA) and used multivariable regression analysis to assess the relationship of cumulative and individual ACEs with asthma severity. Survey sampling weights and SAS survey procedures were implemented to produce nationally representative results.

Results: Our analysis included 3691 children, representing a population of 5,465,926. Unadjusted analysis demonstrated that ACEs - particularly household economic hardship, parent/guardian served time in jail, witnessed household violence, or victim/witness of neighborhood violence - were each associated with higher odds of moderate/severe caregiver-reported asthma. After controlling for confounders possibly associated with both exposure (ACEs) and outcome (asthma severity), children who witnessed parent/adult violence had higher adjusted odds of caregiver-reported moderate/severe asthma. (1.67, confidence interval 1.05-2.64, P = .03) CONCLUSIONS: Intrafamilial witnessed household violence is significantly associated with caregiver-reported moderate/severe asthma.
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http://dx.doi.org/10.1016/j.acap.2021.04.021DOI Listing
August 2021

Caregiver outcomes of a dementia care program.

Geriatr Nurs 2021 Mar-Apr;42(2):447-459. Epub 2021 Mar 11.

Jona Goldrich Center for Alzheimer's and Memory Disorders, Department of Neurology, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd, A6600, Los Angeles, CA 90048, United States.

The University of California, Los Angeles Alzheimer's and Dementia Care (ADC) program enrolls persons living with dementia (PLWD) and their family caregivers as dyads to work with nurse practitioner dementia care specialists to provide coordinated dementia care. At one year, despite disease progression, overall the PLWDs' behavioral and depressive symptoms improved. In addition, at one-year, overall caregiver depression, strain, and distress related to behavioral symptoms also improved. However, not all dyads enrolled in the ADC program showed improvement in these outcomes. We conducted a mixed qualitative-quantitative study to explore why some participants did not benefit and what could be changed in this and other similar dementia management programs to increase the percentage who benefit. Semi-structured interviews (N=12) or surveys (N=41) were completed with 53 caregivers by telephone, mail and online. Seven areas for potential program improvement were identified from the first 12 interviews. These included: recommendations that did not match caregivers' perceived care needs, barriers to accessing care and utilizing resources, differing care needs based on stage of dementia, needing services not offered by the ADC, needing more education or support, behavioral recommendations that the caregiver felt did not work, and poor rapport of the dementia expert with caregivers. Despite having been identified as having had no clinical benefit from participating in the program, most caregivers (85%) reported that the program was very beneficial or extremely beneficial. Respondents identified the close, longitudinal relationship and access to a dementia care expert as particularly beneficial. This dichotomy highlights that perceived benefit for most of the interviewed caregivers was not captured with the formal instruments used by the program.
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http://dx.doi.org/10.1016/j.gerinurse.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084597PMC
March 2021

Growth Failure Prevalence in Neonates with Gastroschisis : A Statewide Cohort Study.

J Pediatr 2021 06 26;233:112-118.e3. Epub 2021 Feb 26.

Division of Neonatology and Developmental Biology, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA.

Objectives: To perform a multicenter study to assess growth failure in hospitalized infants with gastroschisis.

Study Design: This study included neonates with gastroschisis within sites in the University of California Fetal Consortium. The study's primary outcome was growth failure at hospital discharge, defined as a weight or length z score decrease >0.8 from birth. Regression analysis was performed to assess changes in z scores over time.

Results: Among 125 infants with gastroschisis, the median gestational age was 37 weeks (IQR 35-37). Length of stay was 32 days (23-60); 55% developed weight or length growth failure at discharge (28% had weight growth failure, 42% had length growth failure, and 15% had both weight and length growth failure). Weight and length z scores at 14 days, 30 days, and discharge were less than birth (P < .01 for all). Weight and length z scores declined from birth to 30 days (-0.10 and -0.11 z score units/week, respectively, P < .001). Length growth failure at discharge was associated with weight and length z score changes over time (P < .05 for both). Lower gestational age was associated with weight growth failure (OR 0.70 for each gestational age week, 95% CI 0.55-0.89, P = .004).

Conclusions: Growth failure, in particular linear growth failure, is common in infants with gastroschisis. These data suggest the need to improve nutritional management in these infants.
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http://dx.doi.org/10.1016/j.jpeds.2021.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154735PMC
June 2021

Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate (SHARP) Consortium: Analysis of 344 Prospectively Treated Patients.

Int J Radiat Oncol Biol Phys 2021 07 23;110(3):731-737. Epub 2021 Jan 23.

Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California. Electronic address:

Purpose: To explore the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in high-risk prostate cancer (HRPCa) in a consortium of 7 institutional phase 2 trials and prospective registries.

Methods And Materials: Individual patient data were pooled for 344 patients with a minimum follow-up of 24 months. Biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) were estimated using a Kaplan-Meier framework. Fine and Gray competing risk and Cox proportional hazards regression models were developed to assess the association between time to BCR and time to distant metastasis and prespecified variables of interest. Logistic regression models were developed to evaluate associations between acute and late grade ≥2 genitourinary and gastrointestinal and the following a priori-specified variables: age, dose per fraction, ADT use, and nodal radiation therapy.

Results: Median follow-up was 49.5 months. Seventy-two percent of patients received ADT, with a median duration of 9 months, and 19% received elective nodal radiation therapy. Estimated 4-year BCRFS and DMFS rates were 81.7% (95% CI, 77.2%-86.5%) and 89.1% (95% CI, 85.3%-93.1%). The crude incidences of late grade ≥3 genitourinary and gastrointestinal toxicity were 2.3% and 0.9%.

Conclusions: These data support a favorable toxicity and efficacy profile for SBRT for HRPCa. Further prospective studies are needed to evaluate the optimal dose and target volume in the context of SBRT for HRPCa.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.016DOI Listing
July 2021

Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses.

Sci Rep 2021 01 21;11(1):1949. Epub 2021 Jan 21.

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, 1000 Veteran Avenue, Room 1-520, Los Angeles, CA, 90095, USA.

Endothelial cells (EC) coordinate vascular homeostasis and inflammation. In organ transplantation, EC are a direct alloimmune target. We posited that tissue specific heterogeneity of vascular EC may partly underlie the disparate organ-specific alloimmune risk. We examined the vascular endothelial response to inflammation across six primary endothelial beds from four major transplanted organs: the heart, lung, kidney and liver. First, we reanalyzed a public dataset of cardiac allograft rejection and found that endothelial inflammatory response genes were elevated in human cardiac allograft biopsies undergoing rejection compared with stable grafts. Next, the inducible inflammatory phenotypes of EC from heart, lung, kidney, and liver were characterized in vitro, focused on expression of adhesion molecules and chemokines, and recruitment of allogeneic peripheral blood mononuclear immune cells. Large vessel cardiac EC most highly upregulated VCAM-1, particularly compared with hepatic EC, supported greater leukocyte adhesion and had distinct chemokine profiles after stimulation with cytokines and complement. Differentially expressed gene candidates that are known regulators of cytokine signaling and inflammatory programming were verified in publicly available datasets of organ-specific endothelial transcriptomes. In summary, differential baseline expression of immune regulating genes may contribute to differential vascular inflammatory responses depending on organ.
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http://dx.doi.org/10.1038/s41598-020-80102-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820348PMC
January 2021

Validation of a Brief Multi-Dimensional Assessment of Dementia Severity.

J Am Geriatr Soc 2021 02 30;69(2):512-516. Epub 2020 Nov 30.

Department of Medicine, Division of Geriatrics, University of California Los Angeles, Los Angeles, California, USA.

Background/objectives: Briefer measures of symptoms and functional limitations may reduce assessment burden and facilitate monitoring populations of persons with dementia (PWD).

Design: Prospective follow-up study.

Setting: University-based dementia care management program.

Participants: 1,091 PWD.

Measurements: We assessed cognition (Mini Mental State Examination (MMSE)-11 tasks), neuropsychiatric symptom severity (Neuropsychiatric Inventory Questionnaire Severity Scale (NPIQ-S)-12 items), and functional ability (Activities of Daily Living (ADL)-6 items; Functional Activities Questionnaire (FAQ)-10 items). Item response theory was used to select subsets of items by identifying low item discrimination (<1.50), poor item fit (χ ), local dependence (LD), and with difficulty similar to other items. We estimated correlations between original and shorter scales and compared their associations with mortality. We added two symptoms (trouble swallowing, coughing when eating) reflecting late-stage dementia complications, created a multi-dimensional dementia assessment composite, and examined its association with mortality.

Results: Five MMSE tasks were eliminated: two with low discrimination, two with difficulty similar to other items, and one with poor fit. The remaining tasks were correlated with the full MMSE at r = 0.82. We retained three ADLs that were correlated with the total ADL set at r = 0.95 and kept five FAQ items that were not LD (correlation with full FAQ, r = 0.97). Associations with mortality were similar between the longer and shorter scales. A higher score on the composite (range 0-100) indicates worse dementia impact and was associated with mortality (hazard ratio (HR) per scale point: 1.03 (1.02-1.04)).

Conclusion: These brief assessments and dementia composite may reduce administration time while preserving validity.
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http://dx.doi.org/10.1111/jgs.16930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269957PMC
February 2021

The intraprostatic immune environment after stereotactic body radiotherapy is dominated by myeloid cells.

Prostate Cancer Prostatic Dis 2021 03 9;24(1):135-139. Epub 2020 Jul 9.

Radiation Oncology at UCLA, Los Angeles, CA, USA.

Background: Hundreds of ongoing clinical trials combine radiation therapy, mostly delivered as stereotactic body radiotherapy (SBRT), with immune checkpoint blockade. However, our understanding of the effect of radiotherapy on the intratumoral immune balance is inadequate, hindering the optimal design of trials that combine radiation therapy with immunotherapy. Our objective was to characterize the intratumoral immune balance of the malignant prostate after SBRT in patients.

Methods: Sixteen patients with high-risk, non-metastatic prostate cancer at comparable Gleason Grade disease underwent radical prostatectomy with (n = 9) or without (n = 7) neoadjuvant SBRT delivered in three fractions of 8 Gy over 5 days completed 2 weeks before surgery. Freshly resected prostate specimens were processed to obtain single-cell suspensions, and immune-phenotyped for major lymphoid and myeloid cell subsets by staining with two separate 14-antibody panels and multicolor flow cytometry analysis.

Results: Malignant prostates 2 weeks after SBRT had an immune infiltrate dominated by myeloid cells, whereas malignant prostates without preoperative treatment were more lymphoid-biased (myeloid CD45 cells 48.4 ± 19.7% vs. 25.4 ± 7.0%; adjusted p-value = 0.11; and CD45 lymphocytes 51.6 ± 19.7% vs. 74.5 ± 7.0%; p = 0.11; CD3 T cells 35.2 ± 23.8% vs. 60.9 ± 9.7%; p = 0.12; mean ± SD).

Conclusion: SBRT drives a significant lymphoid to myeloid shift in the prostate-tumor immune infiltrate. This may be of interest when combining SBRT with immunotherapies, particularly in prostate cancer.
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http://dx.doi.org/10.1038/s41391-020-0249-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794088PMC
March 2021

Transcriptomic Heterogeneity of Gleason Grade Group 5 Prostate Cancer.

Eur Urol 2020 09 24;78(3):327-332. Epub 2020 May 24.

Department of Urology, University of California, Los Angeles, CA, USA; Department of Human Genetics, University of California, Los Angeles, CA, USA.

Gleason grade group (GG) 5 prostate cancer has been associated with an aggressive natural history, and retrospective data support a role for treatment intensification. However, clinical outcomes remain heterogeneous in this cohort, and intensified treatments carry an increased risk of adverse events. We sought to explore the transcriptomic heterogeneity of GG 5 tumors by querying transcriptomic data from the tumors of 2138 patients with GG 5 disease who underwent prostatectomy. Four distinct consensus clusters were identified with respect to differential transcriptional activation of hallmark pathways, with distinct molecular subtyping profiles and different average genomic risks (AGRs). One cluster, accounting for 325 tumors (15.2% of the population), was enriched for genes related to the cell cycle/proliferation, metabolic pathways, androgen response pathways, and DNA repair, and had a higher AGR than the other clusters (p < 0.001). This clustering, with an identification of a high genomic risk cluster, was subsequently validated in a separate cohort of 1921 patients as well as a third cohort of 201 patients. The latter cohort had outcomes available, and it was found that patients in the high genomic risk cluster had significantly worse distant metastasis-free survival than the other clusters. Tumors in this high genomic risk cluster of GG 5 disease may be particularly likely to benefit from treatment intensification. PATIENT SUMMARY: In this report, we examined differences in gene expression in tumors from men with Gleason grade group 5 prostate cancer. We identified significant diversity, with one specific subgroup of tumors associated with expression profiles that suggest a worse prognosis.
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http://dx.doi.org/10.1016/j.eururo.2020.05.009DOI Listing
September 2020

Adenoma and Advanced Adenoma Detection Rates of Water Exchange, Endocuff, and Cap Colonoscopy: A Network Meta-Analysis with Pooled Data of Randomized Controlled Trials.

Dig Dis Sci 2021 04 25;66(4):1175-1188. Epub 2020 May 25.

David Geffen School of Medicine, University of California, Los Angeles, 757 Westwood Plaza, Suite 7236, Los Angeles, CA, 90095-7417, USA.

Background And Aims: A network meta-analysis showed that low-cost optimization of existing resources was as effective as distal add-on devices in increasing adenoma detection rate (ADR). We assessed the impacts of water exchange (WE), Endocuff, and cap colonoscopy on ADR and advanced adenoma detection rate (AADR). We hypothesized that WE may be superior at improving ADR and AADR.

Methods: The literature was searched for all randomized controlled trials (RCTs) that reported ADR as an outcome and included the keywords colonoscopy, and water exchange, Endocuff, or cap. We performed traditional network meta-analyses with random effect models comparing ADR and AADR of each method using air insufflation (AI) as the control and reported the odds ratios with 95% confidence interval. Performances were ranked based on P-score.

Results: Twenty-one RCTs met inclusion criteria. Fourteen RCTs also reported AADR. Both WE [1.46 (1.20-1.76)] and Endocuff [1.39 (1.17-1.66)] significantly increase ADR, while cap has no impact on ADR [1.00 (0.82-1.22)]. P-scores for WE (0.88), Endocuff (0.79), cap (0.17), and AI (0.17) suggest WE has the highest ADR. WE [1.38 (1.12-1.70)], but not Endocuff [0.96 (0.76-1.21)] or cap [1.06 (0.85-1.32)], significantly increases AADR. P-scores for WE (0.98), cap (0.50), AI (0.31), and Endocuff (0.21) suggest WE is more effective at increasing AADR. The results did not change after adjusting for age, proportion of males, and withdrawal time.

Conclusion: WE may be the modality of choice to maximally improve ADR and AADR.
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http://dx.doi.org/10.1007/s10620-020-06324-0DOI Listing
April 2021

Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa, Busulfan, and Cyclophosphamide Conditioning Regimen.

Clin Lymphoma Myeloma Leuk 2020 07 20;20(7):468-479. Epub 2020 Feb 20.

Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.

Background: High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and non-Hodgkin lymphoma (NHL) with CNS involvement and has shown promising results.

Patients And Methods: A retrospective analysis was performed of 48 consecutive patients who had undergone HDC/ASCT with TBC (thiotepa, busulfan, cyclophosphamide) conditioning for PCNSL (27 patients), secondary CNS lymphoma (SCNSL) (8 patients), or relapsed disease with CNS involvement (13 patients) from July 2006 to December 2017. Of the 27 patients with PCNSL, 21 had undergone ASCT at first complete remission (CR1).

Results: The 2-year progression-free survival (PFS) rate was 80.5% (95% confidence interval [CI], 69.9-92.9) and the 2-year overall survival (OS) rate was 80.1% (95% CI, 69.2%-92.7%) among all patients. The 2-year PFS and OS rate for patients with PCNSL in CR1 was 95.2% (95% CI, 86.6%-100%) and 95.2% (95% CI, 86.6%-100%), respectively. On univariate analysis of the patients with PCNSL, ASCT in CR1 was the only variable statistically significant for outcome (P = .007 for PFS; P = .008 for OS). Among patients with SCNSL or CNS relapse, the 2-year PFS and OS rate were comparable at 75.9% (95% CI, 59.5%-96.8%) and 75.3% (95% CI, 58.6%-98.6%), respectively. The most common side effects were febrile neutropenia (89.6%; of which 66.7% had an infectious etiology identified), nausea/vomiting (85.4%), diarrhea (93.8%), mucositis (89.6%), and electrolyte abnormalities (89.6%). Four patients (8.3%) died of treatment-related overwhelming infection; of these patients, 3 had SCNSL.

Conclusion: HDC and ASCT using TBC conditioning for both PCNSL and secondary CNS NHL appears to have encouraging long-term efficacy with manageable side effects.
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http://dx.doi.org/10.1016/j.clml.2020.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138188PMC
July 2020

Tumor Size Matters-Understanding Concomitant Tumor Immunity in the Context of Hypofractionated Radiotherapy with Immunotherapy.

Cancers (Basel) 2020 Mar 18;12(3). Epub 2020 Mar 18.

Department of Radiation Oncology, University of California at Los Angeles (UCLA), Los Angeles, CA 90095-1714, USA.

The purpose of this study was to determine the dynamic contributions of different immune cell subsets to primary and abscopal tumor regression after hypofractionated radiation therapy (hRT) and the impact of anti-PD-1 therapy. A bilateral syngeneic FSA1 fibrosarcoma model was used in immunocompetent C3H mice, with delayed inoculation to mimic primary and microscopic disease. The effect of tumor burden on intratumoral and splenic immune cell content was delineated as a prelude to hRT on macroscopic T1 tumors with 3 fractions of 8 Gy while microscopic T2 tumors were left untreated. This was performed with and without systemic anti-PD-1. Immune profiles within T1 and T2 tumors and in spleen changed drastically with tumor burden in untreated mice with infiltrating CD4+ content declining, while the proportion of CD4+ Tregs rose. Myeloid cell representation escalated in larger tumors, resulting in major decreases in the lymphoid:myeloid ratios. In general, activation of Tregs and myeloid-derived suppressor cells allow immunogenic tumors to grow, although their relative contributions change with time. The evidence suggests that primary T1 tumors self-regulate their immune content depending on their size and this can influence the lymphoid compartment of T2 tumors, especially with respect to Tregs. Tumor burden is a major confounding factor in immune analysis that has to be taken into consideration in experimental models and in the clinic. hRT caused complete local regression of primary tumors, which was accompanied by heavy infiltration of CD8+ T cells activated to express IFN-γ and PD-1; while certain myeloid populations diminished. In spite of this active infiltrate, primary hRT failed to generate the systemic conditions required to cause abscopal regression of unirradiated microscopic tumors unless PD-1 blockade, which on its own was ineffective, was added to the RT regimen. The combination further increased local and systemically activated CD8+ T cells, but few other changes. This study emphasizes the subtle interplay between the immune system and tumors as they grow and how difficult it is for local RT, which can generate a local immune response that may help with primary tumor regression, to overcome the systemic barriers that are generated so as to effect immune regression of even small abscopal lesions.
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http://dx.doi.org/10.3390/cancers12030714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140082PMC
March 2020

Growth from Birth to 30 months for Infants Born with Congenital Gastrointestinal Anomalies and Disorders.

Am J Perinatol 2021 08 13;38(S 01):e33-e38. Epub 2020 Mar 13.

Division of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Mattel Children's Hospital at UCLA, Los Angeles, California.

Objective: This study aimed to investigate growth among neonates with gastrointestinal disorders.

Study Design: Inclusion criteria included neonates with gastroschisis, omphalocele, intestinal atresia, tracheoesophageal fistula, Hirschsprung's disease, malabsorption disorders, congenital diaphragmatic hernia, and imperforate anus born between 2010 and 2018. Anthropometrics were collected for the first 30 months, and a subgroup analysis was performed for gastroschisis infants.

Results: In 61 subjects, 13% developed severe growth failure within the first month. One-, four-, and nine-month weight and length -scores were less than birth weight in all infants ( < 0.05). In infants with gastroschisis, a similar pattern was observed for weight -scores only ( < 0.05). From birth to 15 months, head circumference -score increased over time in all infants ( = 0.001), while in gastroschisis infants, weight, length, and head circumference -scores increased over time ( < 0.05).

Conclusion: In a cohort of infants with gastrointestinal disorders, growth failure was followed by catch-up growth.
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http://dx.doi.org/10.1055/s-0040-1705136DOI Listing
August 2021

Disease characteristics of diffuse large B-cell lymphoma predicting relapse and survival after autologous stem cell transplantation: A single institution experience.

Hematol Oncol 2020 Feb 3;38(1):38-50. Epub 2019 Dec 3.

Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.

While various tools such as the International Prognostic Index (IPI) and its derivatives exist for risk-stratification of diffuse large B-cell lymphoma (DLBCL) at diagnosis, patient and disease characteristics capable of predicting outcome after high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) are not clearly defined. We retrospectively analyzed medical records of 111 DLBCL patients (78 relapsed and 33 refractory) who underwent HDC/ASCT at our institution from 2010-2015. After a median follow-up time of 4.6 years (interquartile range [IQR] 2.2-8.1), the likelihood of 5-year progression-free survival (PFS) was 62.2% (95% CI, 53.4%-72.4%) and the likelihood of 5-year overall survival (OS) was 68.9% (95% CI, 60.7%-78.2%). More than three chemotherapy regimens prior to ASCT was the only variable associated with lower likelihood of PFS (P = .004) and OS (P = 0.026). Male gender and high IPI score at time of ASCT were also associated with lower likelihood of PFS (P = .043; P = .013). NCCN IPI and age-adjusted IPI at time of ASCT were not predictive of outcome following ASCT. Patients with refractory and relapsed disease had similar outcomes post-ASCT (P = .207 for PFS, P = .073 for OS).
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http://dx.doi.org/10.1002/hon.2690DOI Listing
February 2020

Association Between Neonatal Neuroimaging and Clinical Outcomes in Zika-Exposed Infants From Rio de Janeiro, Brazil.

JAMA Netw Open 2019 07 3;2(7):e198124. Epub 2019 Jul 3.

Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Importance: Congenital Zika virus (ZIKV) infection may present with a spectrum of clinical and neuroradiographic findings.

Objective: To determine whether neuroimaging findings for infants with a history of ZIKV exposure are associated with infant clinical outcomes and gestational age at antenatal ZIKV infection.

Design, Setting, And Participants: This cohort study retrospectively reviewed neuroimaging results (computed tomography and/or magnetic resonance imaging scans) of 110 ZIKV-exposed infants from a maternity and children's hospital in Rio de Janeiro, Brazil, following the 2015 to 2016 ZIKV epidemic. Neuroimaging from March 1, 2016, to June 30, 2017, was evaluated to determine whether findings were associated with clinical outcomes and the timing of maternal ZIKV infection. Data were analyzed from July 1, 2017, to August 30, 2018.

Exposures: Neuroimaging (computed tomography and/or magnetic resonance imaging) was performed on ZIKV-exposed infants after birth. Blood and/or urine specimens from mothers and infants were tested for ZIKV by polymerase chain reaction assay.

Main Outcomes And Measures: Neuroimaging studies were evaluated for structural abnormalities and other forms of brain injury.

Results: A total of 110 infants with a mean (SD) gestational age of 38.4 (2.1) weeks had neuroimaging and clinical outcome data reviewed. Of these, 71 (65%) had abnormal neuroimaging findings, with the majority (96%) classified as having severe ZIKV infection at birth. The most common neuroimaging abnormalities were structural abnormalities including brain calcifications, especially at the cortico-subcortical white matter junction, cortex malformations, ventriculomegaly, and reduced brain volumes, followed by brainstem hypoplasia, cerebellar hypoplasia, and corpus callosum abnormalities. Frequency of abnormal imaging was higher in infants with specific clinical findings as opposed to those without them; these findings included fetal brain disruption sequence (100% vs 35%), microcephaly (100% vs 30%), congenital contractures (100% vs 58%), ophthalmologic abnormalities (95% vs 44%), hearing abnormalities (100% vs 58%), and neurologic symptoms (94% vs 10%). Four of 39 infants (10%) without initial evidence of severe ZIKV infection and normal findings on neurologic evaluation at birth had abnormal neuroimaging findings. Neuroimaging abnormalities differed by trimester of maternal ZIKV infection, with 63% of infants born to mothers infected in the first trimester, 13% of infants born to mothers infected in the second trimester, and 1% of infants born to mothers infected in the third trimester exhibiting neuroimaging abnormalities. The odds of abnormal neuroimaging were 7.9 times greater for infants with first trimester ZIKV exposure compared with other trimesters combined (odds ratio, 7.9; 95% CI, 3.0-20.4; P < .001).

Conclusions And Relevance: Neuroimaging abnormalities of computed tomography and/or magnetic resonance imaging scans were common in ZIKV-exposed infants. While neuroimaging abnormalities were seen in 10% of infants without clinically severe ZIKV, most occurred almost exclusively among those with clinically severe ZIKV, especially among those with a history of ZIKV exposure in the first trimester.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.8124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669783PMC
July 2019

Patient and Caregiver Benefit From a Comprehensive Dementia Care Program: 1-Year Results From the UCLA Alzheimer's and Dementia Care Program.

J Am Geriatr Soc 2019 11 29;67(11):2267-2273. Epub 2019 Jul 29.

Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

Background/objectives: Persons with Alzheimer disease and related dementias (ADRDs) require comprehensive care that spans health systems and community-based organizations. This study examined the clinical outcomes of a comprehensive dementia care program and identified subgroups who were more likely to benefit.

Design: Observational, baseline and 1 year after intervention.

Setting: Urban, academic medical center.

Participants: A total of 554 persons with dementia and their caregivers who had 1-year follow-up evaluations and data on clinical outcomes.

Intervention: Health system-based comprehensive dementia care management program using nurse practitioner dementia care managers.

Measurements: Patient measures included the Mini-Mental State Examination (MMSE), the Functional Activities Questionnaire, Basic and Instrumental Activities of Daily Living scales, the Cornell Scale for Depression in Dementia, and the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity. Caregiver measures included the Modified Caregiver Strain Index, the Patient Health Questionnaire-9, NPI-Q Distress, and the Dementia Burden Scale-Caregiver). We used established minimal clinically important differences and lowest tertiles of baseline symptoms to define improving symptoms and maintaining low symptoms as clinical benefit for patients and caregivers.

Results: At year 1, persons with ADRD improved on all scales, except MMSE and functional status measures; caregivers improved on all scales. Using validated instruments, 314/543 (58%) of patients, 282/447 (63%) of caregivers, and 376/501 (75%) of patients or caregivers demonstrated clinical benefit. In adjusted multivariate models, at year 1, more behavioral symptoms and fewer depression symptoms at baseline were associated with patient improvement; and fewer baseline depression symptoms were associated with maintaining low behavioral symptoms. Male caregiver sex, higher baseline caregiver burden, and caring for patients with fewer baseline depression symptoms were associated with caregiver improvement. Male caregiver sex and patients with fewer depression symptoms, fewer behavioral symptoms, and more functional impairment at baseline were associated with caregivers maintaining low burden at 1 year.

Conclusions: Health system-based comprehensive dementia care management is a promising approach to improving clinical outcomes, with benefits for both patients and caregivers. J Am Geriatr Soc 67:2267-2273, 2019.
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http://dx.doi.org/10.1111/jgs.16085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861615PMC
November 2019

Early Clinical Infancy Outcomes for Microcephaly and/or Small for Gestational Age Zika-Exposed Infants.

Clin Infect Dis 2020 06;70(12):2663-2672

Department of Biostatistics, David Geffen School of Medicine, University of California-Los Angeles, California, USA.

Background: Zika-exposed infants with microcephaly (proportional or disproportional) and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.Antenatal Zika virus (ZIKV) exposure may lead to adverse infant outcomes including microcephaly and being small for gestational age (SGA). ZIKV-exposed infants with a diagnosis of microcephaly (proportional [PM] or disproportional [DM]) or SGA at birth were evaluated with anthropometric measurements and health outcomes.

Methods: Infants had laboratory-confirmed ZIKV exposure in Brazil. PM, DM, or SGA classification was based on head circumference and weight. First-year growth parameters and clinical outcomes were recorded with analyses performed.

Results: Among the 156 ZIKV-exposed infants, 14 (9.0%) were SGA, 13 (8.3%) PM, 13 (8.3%) DM, and 116 (74.4%) were neither SGA nor had microcephaly (NSNM). High rates of any neurologic, ophthalmologic, and hearing abnormalities were observed for PM (100%), DM (100%), and SGA (42.9%) vs NSNM infants (18.3%; P <.001); odds ratio [OR], 3.4 (95% confidence interval [CI], 1.1-10.7) for SGA vs NSNM. Neuroimaging abnormalities were seen in 100% of PM and DM and in 42.9% of SGA vs NSNM infants 16%; (P <.001); OR 3.9 (95% CI, 1.2-12.8) for SGA vs NSNM. Growth rates by z score, particularly for microcephaly infants, were poor after birth but showed improvement beyond 4 months of life.

Conclusions: ZIKV-exposed infants with microcephaly (PM and DM) had similarly high rates of adverse outcomes but showed improvement in growth measurements beyond 4 months of life. While SGA infants had fewer adverse outcomes compared with microcephaly infants, notable adverse outcomes were observed in some; their odds of having adverse outcomes were 3 to 4 times greater compared to NSNM infants.Zika-exposed infants with microcephaly, irrespective of being proportional or disproportional, and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.
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http://dx.doi.org/10.1093/cid/ciz704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286378PMC
June 2020

The Effect of a Comprehensive Dementia Care Management Program on End-of-Life Care.

J Am Geriatr Soc 2019 03 24;67(3):443-448. Epub 2019 Jan 24.

Multicampus Program in Geriatric Medicine and Gerontology, David Geffen School Medicine, University of California, Los Angeles, California.

Background/objectives: Although Alzheimer disease and other dementias are life limiting, only a minority of these patients or their proxy decision makers participate in advance care planning. We describe end-of-life care preferences and acute care and hospice use in the last 6 months of life for persons enrolled in a comprehensive dementia care management program.

Design: Observational, retrospective cohort.

Setting: Urban, academic medical center.

Participants: A total of 322 persons enrolled in dementia care management after July 1, 2012, who died before July 1, 2016.

Intervention: Dementia care comanagement model using nurse practitioners partnered with primary care providers and community organizations to provide comprehensive dementia care, including advance care planning.

Measurements: Advance care preferences, use of Physician Orders for Life Sustaining Treatment (POLST), hospice enrollment, and hospitalizations and emergency department (ED) visits in the last 6 months of life obtained from electronic health record data.

Results: Nearly all decedents (99.7%, N = 321) had a goals-of-care conversation documented (median = 3 conversations; interquartile range = 2-4 conversations), and 64% had advance care preferences recorded. Among those with recorded preferences, 88% indicated do not resuscitate, 48% limited medical interventions, and 35% chose comfort-focused care. Most patients (89%) specified limited artificial nutrition, including withholding feeding tubes. Over half (54%) had no hospitalizations or ED visits in the last 6 months of life, and intensive care unit stays were rare (5% of decedents). Overall, 69% died on hospice. Decedents who had completed a POLST were more likely to die in hospice care (74% vs 62%; P = .03) and die at home (70% vs 59%; P = .04).

Conclusions: Enrollees in a comprehensive dementia care comanagement program had high engagement in advance care planning, high rates of hospice use, and low acute care utilization near the end of life. Wider implementation of such programs may improve end-of-life care for persons with dementia. J Am Geriatr Soc 67:443-448, 2019.
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http://dx.doi.org/10.1111/jgs.15769DOI Listing
March 2019

Obese- and allergic-related asthma phenotypes among children across the United States.

J Asthma 2019 05 3;56(5):512-521. Epub 2018 Jul 3.

a University of California, Pediatrics, Pediatric Pulmonology , Los Angeles , California , United States.

Objectives: Pediatric asthma is heterogeneous with phenotypes that reflect differing underlying inflammation and pathophysiology. Little is known about the national prevalence of certain obesity- and allergy-related asthma phenotypes or associated characteristics. We therefore assessed the national prevalence, risk factors, and caregiver-reported severity of four asthma phenotypes: not-allergic-not-obese, allergic-not-obese, obese-not-allergic, and allergic-and-obese.

Methods: We analyzed data from the 2007-2008 National Survey of Children's Health (NSCH) of 10-17 year-olds with caregiver-reported asthma. We described sociodemographic and health risk factors of each phenotype and then applied logistic and ordinal regression models to identify associated risk factors and level of severity of the phenotypes.

Results: Among 4427 children with asthma in this NSCH cohort, the association between race and phenotype was statistically significant (p < 0.0001); white children with asthma were most likely to have allergic-not-obese asthma while black and Hispanic children with asthma were most likely to have the obese-nonallergic phenotype (p < 0.001). Attention-deficit disorder/attention-deficit hyperactivity disorder was more likely to be present in allergic-not-obese children (odds ratio (OR) 1.50, confidence interval (CI) 1.14-1.98, p = 0.004). The phenotype with the highest risk for more severe compared to mild asthma was the obese-and-allergic asthma phenotype (OR 3.34, CI 2.23-5.01, p < 0.001).

Conclusions: Allergic-not-obese asthma comprised half of our studied asthma phenotypes, while obesity-related asthma (with or without allergic components) comprised one-fifth of asthma phenotypes in this cohort representative of the US population. Children with both obese and allergic asthma are most likely to have severe asthma. Future management of childhood asthma might consider more tailoring of treatment and management plans based upon different childhood asthma phenotypes.
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http://dx.doi.org/10.1080/02770903.2018.1466317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195487PMC
May 2019
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