Effectiveness and safety of tacrolimus with or without eltrombopag, as a part of immunosuppressive treatment of aplastic anemia in adults: a retrospective case series.

First-line treatment of aplastic anemia(AA) and for AA patients ineligible for hematopoietic stem cell transplantation (HSCT) has consisted of antithymocyte globulin (ATG), the calcineurin inhibitor cyclosporine A (CsA), and more recently eltrombopag. However, at our institution, we have successfully substituted another calcineurin inhibitor, tacrolimus, as a part of immunosuppressive threatment (IST) for AA due to more favorable toxicity profile. Since there is limited data on the use of tacrolimus in aplastic anemia, we conducted a retrospective review of twenty patients treated with tacrolimus-based immunosuppressive therapy (IST) as a first- or second-line treatment. The overall response rate was comparable to that of patients treated with CsA (18 patients). However, there were no cutaneous side effects observed in patients receiving tacrolimus, a relatively common finding with CsA use. Our data suggest that tacrolimus-based IST is a potential option in AA and might have a more favorable toxicity profile compared to CsA.

Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation.

Telomeres are repetitive DNA sequences that protect the ends of linear chromosomes, and they are maintained by a ribonucleoprotein complex called telomerase. Variants in genes encoding for telomerase components have been associated with a spectrum of disease in the lung, skin, bone marrow, and liver. Mutations in the telomerase reverse transcriptase and telomerase RNA component genes have been observed at a higher prevalence in patients with liver disease compared with the general population; however, the presence of variants in other components of the telomerase complex and their impact on clinical outcomes has not been explored. We evaluated 86 patients with end-stage liver disease for variants in an expanded panel of eight genes, and found that 17 patients (20%) had likely deleterious variants by in silico analysis. Seven unique likely deleterious variants were identified in the regulator of telomere elongation helicase 1 (RTEL1) gene that encodes for a DNA helicase important in telomere maintenance and genomic stability. In gene burden association analysis of their clinical data, the presence of any RTEL1 variant was associated with a 29% lower baseline white blood cell count (95% confidence interval [CI], -7% to -46%; P Value = 0.01) compared with patients without RTEL1 variants, and the presence of any exonic missense RTEL1 variant was associated with a 42% lower baseline platelet count (95% CI, -5% to -65%: P Value = 0.03). The presence of any telomerase variant was associated with an increased number of readmissions within 1 year after transplantation demonstrated by an incident rate ratio (IRR) of 3.15 (95% CI, 1.22 to 8.57). No association with survival was observed. Conclusion: Among patients who underwent liver transplantation, the presence of any exonic missense variant was associated with a longer postoperative length of stay with an IRR of 2.16 (95% CI, 1.31 to 3.68).

Cardiac birth defects in a twin infant born to a woman with chronic myeloid leukemia on dasatinib.

Preclinical animal studies have demonstrated an association between maternal use of tyrosine kinase inhibitors and embryofetal toxicity; yet, multiple clinical case series have reported normal pregnancy outcomes and healthy infants in women on these medications during the course of their pregnancy. We describe a case of a woman with chronic myeloid leukemia who had taken the second-generation tyrosine kinase inhibitor dasatinib during the first 12 weeks of her dichorionic diamniotic twin pregnancy and subsequently delivered two low-birth weight infants, one with severe cardiac malformations and the other without apparent birth abnormalities. To our knowledge, this is the first reported case of fetal cardiovascular defects in an infant born to a woman on dasatinib during a twin pregnancy and supports current recommendations to avoid this medication during pregnancy. We also review relevant preclinical and clinical studies of tyrosine kinase inhibitor use during pregnancy and explore alternative therapeutic options for patients with chronic myeloid leukemia during pregnancy to aid clinicians in the appropriate management of these patients so as to minimize both maternal and fetal risks.

Management of the Incidental Pulmonary Embolism.

OBJECTIVE: The incidental pulmonary embolism (PE) is being identified at an increasing rate because of use of MDCT and presents a management challenge because of a lack of prospective data. Most clinicians treat patients with proximal or segmental incidental PE in the same manner as patients with suspected PE. CONCLUSION: The treatment of subsegmental PE may be guided by an assessment of patient symptoms, risk factors for recurrent venous thrombosis, and concomitant deep venous thrombosis.

Hispanic/Latino Ethnicity is an Independent Predictor of Worse Survival for Gastric Cancer in a Multicenter Safety-Net Patient Population.

BACKGROUND: Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients. METHODS: We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016 to December 31, 2020 within Los Angeles County's safety-net hospital system. Gastric cancer-specific survival was compared between the two cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. RESULTS: 448 patients who received care from five medical centers were included. 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34-2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs 60.7 years, p <0.01), demonstrate higher state area deprivation index (6.4 vs 5.0, p <0.01), and present with metastatic disease (59.8% vs 45%, p =0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival (HR 1.56, [95% CI 1.06-2.28], p = 0.02). CONCLUSIONS: Hispanic patients treated within a large, multi-center safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors. IMPACT: Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care.

Rare malignant glomus tumor of the esophagus with pulmonary metastasis: a case report.

Background: Glomus tumors are typically benign soft tissue neoplasms that arise in peripheral cutaneous structures. Visceral organ involvement is exceedingly rare. Case Description: Here we present a case of malignant glomus tumor of the esophagus with pulmonary metastases in a 57-year-old woman presenting with three weeks of progressive dysphagia, epigastric pain, and 35-pound weight loss. Upper endoscopy revealed a 5×3.5×2.5 cm vascular esophageal mass. Contrast-enhanced CT showed multiple, scattered sub-centimeter pulmonary nodules bilaterally. Diagnosis of metastatic glomus tumor was confirmed immunohistochemically on primary tumor and lung biopsies. Localized resection was not feasible due to the patient's poor condition. A trial of gemcitabine and docetaxel was planned, but the patient experienced rapid clinical deterioration after a single dose of gemcitabine before electing for hospice care. Conclusions: We have reviewed the 11 other published cases of esophageal glomus tumors, only one of which was similarly metastatic at time of presentation. Of those patients with localized disease treated with surgical excision, all were alive and had no evidence of recurrence (NER) at their times of publication. In contrast, disease ultimately progressed despite surgery and chemoradiotherapy in the sole other case of metastatic glomus tumor of the esophagus. Although glomus tumors are largely benign entities, this case highlights their rare and aggressive malignant potential.

Medical care needs of returning veterans with PTSD: their other burden.

BACKGROUND: There has been considerable focus on the burden of mental illness (including post-traumatic stress disorder, PTSD) in returning Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans, but little attention to the burden of medical illness in those with PTSD. OBJECTIVES: (1) Determine whether the burden of medical illness is higher in women and men OEF/OIF veterans with PTSD than in those with No Mental Health Conditions (MHC). (2) Identify conditions common in those with PTSD. DESIGN: Cross-sectional study using existing databases (Fiscal Year 2006-2007). SETTING: Veterans Health Administration (VHA) patients nationally. PATIENTS: All 90,558 OEF/OIF veterans using VHA outpatient care nationally, categorized into strata: PTSD, Stress-Related Disorders, Other MHCs, and No MHC. MEASUREMENTS: (1) Count of medical conditions; (2) specific medical conditions (from ICD9 codes, using Agency for Health Research and Quality's Clinical Classifications software framework). MAIN RESULTS: The median number of medical conditions for women was 7.0 versus 4.5 for those with PTSD versus No MHC (p<0.001), and for men was 5.0 versus 4.0 (p<0.001). For PTSD patients, the most frequent conditions among women were lumbosacral spine disorders, headache, and lower extremity joint disorders, and among men were lumbosacral spine disorders, lower extremity joint disorders, and hearing problems. These high frequency conditions were more common in those with PTSD than in those with No MHC. CONCLUSIONS: Burden of medical illness is greater in women and men OEF/OIF veteran VHA users with PTSD than in those with No MHC. Health delivery systems serving them should align clinical program development with their medical care needs.

Characterizing the relationships between tertiary and community cancer providers: Results from a survey of medical oncologists in Southern California.

BACKGROUND: Tertiary cancer centers offer clinical expertise and multi-modal approaches to treatment alongside the integration of research protocols. Nevertheless, most patients receive their cancer care at community practices. A better understanding of the relationships between tertiary and community practice environments may enhance collaborations and advance patient care. METHODS: A 31-item survey was distributed to community and tertiary oncologists in Southern California using REDCap. Survey questions assessed the following attributes: demographics and features of clinical practice, referral patterns, availability and knowledge of clinical trials and precision medicine, strategies for knowledge acquisition, and integration of community and tertiary practices. RESULTS: The survey was distributed to 98 oncologists, 85 (87%) of whom completed it. In total, 52 (61%) respondents were community practitioners and 33 (38%) were tertiary oncologists. A majority (56%) of community oncologists defined themselves as general oncologists, whereas almost all (97%) tertiary oncologists reported a subspecialty. Clinical trial availability was the most common reason for patient referrals to tertiary centers (73%). The most frequent barrier to tertiary referral was financial considerations (59%). Clinical trials were offered by 97% of tertiary practitioners compared to 67% of community oncologists (p = 0.001). Most oncologists (82%) reported only a minimal-to-moderate understanding of clinical trials available at regional tertiary centers. CONCLUSIONS: Community oncologists refer patients to tertiary centers primarily with the intent of clinical trial enrollment; however, significant gaps exist in their knowledge of trial availability. Our results identify the need for enhanced communication and collaboration between community and tertiary providers to expand patients' access to clinical trials.

Altered balance of proteolytic isoforms of pro-brain-derived neurotrophic factor in autism.

Defects in synaptic development and plasticity may lead to autism. Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptogenesis and synaptic plasticity. BDNF is synthesized as a precursor, pro-BDNF, which can be processed into either a truncated form or into mature BDNF. Previous studies reported increased BDNF-immunoreactive protein in autism, but the mechanism of this increase has not been investigated. We examined BDNF mRNA by real-time reverse transcription-polymerase chain reaction and BDNF protein by Western blotting and enzyme-linked immunosorbent assay in postmortem fusiform gyrus tissue from 11 patients with autism and 14 controls. BDNF mRNA levels were not different in the autism versus control samples, but total BDNF-like immunoreactive protein, measured by enzyme-linked immunosorbent assay, was greater in autism than in controls. Western blotting revealed greater pro-BDNF and less truncated BDNF in autism compared with controls. These data demonstrate that increased levels of BDNF-immunoreactive protein in autism are not transcriptionally driven. Increased pro-BDNF and reduced truncated BDNF are consistent with defective processing of pro-BDNF to its truncated form. Distortion of the balance among the 3 BDNF isoforms, each of which may exhibit different biological activities, could lead to changes in connectivity and synaptic plasticity and, hence, behavior. Thus, imbalance in proteolytic isoforms is a possible new mechanism for altered synaptic plasticity leading to autism.

Mental illness and warfarin use in atrial fibrillation.

OBJECTIVES: To determine whether atrial fibrillation (AF) patients with mental health conditions (MHCs) were less likely than AF patients without MHCs to be prescribed warfarin and, if receiving warfarin, to maintain an International Normalized Ratio (INR) within the therapeutic range. STUDY DESIGN: Detailed chart review of AF patients using a Veterans Health Administration (VHA) facility in 2003. METHODS: For a random sample of 296 AF patients, records identified clinician-diagnosed MHCs (independent variable) and AF-related care in 2003 (dependent variables), receipt of warfarin, INR values below/above key thresholds, and time spent within the therapeutic range (2.0-3.0) or highly out of range. Differences between the MHC and comparison groups were examined using X2 tests and logistic regression controlling for age and comorbidity. RESULTS: Among warfarin-eligible AF patients (n = 246), 48.5% of those with MHCs versus 28.9% of those without MHCs were not treated with warfarin (P = .004). Among those receiving warfarin and monitored in VHA, highly supratherapeutic INRs were more common in the MHC group; for example, 27.3% versus 1.6% had any INR >5.0 (P <.001). Differences persisted after adjusting for age and comorbidity. CONCLUSIONS: MHC patients with AF were less likely than those without MHC to have adequate management of their AF care. Interventions directed at AF patients with MHC may help to optimize their outcomes.

Gender disparities in Veterans Health Administration care: importance of accounting for veteran status.

BACKGROUND: In an effort to assess and reduce gender-related quality gaps, the Veterans Health Administration (VHA) has promoted gender-based research. Historically, such appraisals have often relied on secondary databases, with little attention to methodological implications of the fact that VHA provides care to some nonveteran patients. OBJECTIVES: To determine whether conclusions about gender differences in utilization and cost of VHA care change after accounting for veteran status. DESIGN: Cross-sectional. SUBJECTS: All users of VHA in 2002 (N = 4,429,414). MEASURES: Veteran status, outpatient/inpatient utilization and cost, from centralized 2002 administrative files. RESULTS: Nonveterans accounted for 50.7% of women (the majority employees) but only 3.0% of men. Among all users, outpatient and inpatient utilization and cost were far lower in women than in men, but in the veteran subgroup these differences decreased substantially or, in the case of use and cost of outpatient care, reversed. Utilization and cost were very low among women employees; women spouses of fully disabled veterans had utilization and costs similar to those of women veterans. CONCLUSIONS: By gender, nonveterans represent a higher proportion of women than of men in VHA, and some large nonveteran groups have low utilization and costs; therefore, conclusions about gender disparities change substantially when veteran status is taken into account. Researchers seeking to characterize gender disparities in VHA care should address this methodological issue, to minimize risk of underestimating health care needs of women veterans and other women eligible for primary care services.