Sickle Cell Screening in Adults: A Current Review of Point-of-Care Testing.

In adults, the sickle cell solubility test (SCST) is the most common screening test to determine the presence of hemoglobin S (HbS) within a blood sample. The assay is inexpensive, rapid, highly sensitive and specific. However, the SCST cannot accurately quantify the level of HbS in a test sample and requires confirmatory testing to distinguish between sickle trait and sickle cell disease. Despite these limitations, it remains the standard screening tool for HbS in a variety of settings such as screening in the US military or by the National Collegiate Athletic Association. With an increased awareness of the importance of screening for sickle cell in adults, we herein describe the current sensitivity, specificity, positive predictive value, and negative predictive value of this test. We also review overall clinical utility of this laboratory measure and briefly discuss new point-of-care techniques designed to overcome the SCST's shortcomings.

A pilot trial of Thymalfasin (Ta1) to prevent covid-19 infection and morbidities in renal dialysis patients: Preliminary report.

PURPOSE: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are considered particularly susceptible to infection with SARS-CoV2 on the basis of the immunodeficiency associated with advanced age, comorbidity burden, medication use, and need for frequent visits to dialysis clinics. In prior studies, thymalfasin (thymosin alpha 1, Ta1) has been shown to enhance antibody response to influenza vaccine and reduce influenza infection in geriatric populations, including hemodialysis patients, when used as an adjunct to influenza vaccine. Early in the COVID-19 pandemic we speculated that administration of Ta1 to HD patients would result in reduced rate and severity of COVID-19 infection. We also hypothesized that HD patients treated with Ta1 who did become infected with COVID-19 would have a milder course of infection in terms of hospitalization rates, requirement for and length of ICU stays, requirement for mechanical ventilation, and survival. Further, we proposed that patients who avoided COVID-19 infection during the study would have decreased non-COVID-19 infections and hospitalizations compared to controls. PROCEDURES: The study launched in January 2021 and, as of July 1, 2022, 254 ESRD/ HD patients from five dialysis centers in Kansas City, MO have been screened. Of these, 194 patients have been randomized 1:1 to either Group A (1.6 mg Ta1 given subcutaneously twice weekly for 8 weeks), or Group B (control group not receiving Ta1). After the 8-week treatment period, subjects were followed for an additional 4 months and monitored for safety and efficacy. A data safely monitoring board reviewed all reported adverse effects and commented on study progress. RESULTS: To date, only 3 deaths have occurred in subjects treated with Ta1 (Group A), compared to 7 in the control (Group B). There have been 12 COVID-19 related serious adverse effects (SAEs; 5 in Group A, and 7 in Group B). The majority of patients have received a COVID-19 vaccine (91 patients in group A, and 76 patients in Group B) at various times throughout the study. Nearing completion of the study, blood samples have been collected and antibody responses to COVID-19 will be analyzed along with safety and efficacy endpoints when all subjects have completed the study.

Hemoglobin and End-Organ Damage in Individuals with Sickle Cell Disease.

Background: Sickle cell disease (SCD) is an inherited, chronic, multifaceted blood disorder. Patients with SCD develop anemia, which has been associated with end-organ damage (EOD). Objectives: This retrospective, observational, repeated-measures study systematically characterizes the relationship between hemoglobin (Hb) level and EOD in adolescent and adult patients with SCD. Methods: The study population comprised patients with SCD aged ≥12 years with available Hb data from a US provider-centric health care database. For each patient, each Hb value over time was included as a separate observation. Study outcomes-the onset of any new EOD, including chronic kidney disease, pulmonary hypertension, stroke, and leg ulcer-were ascertained during the 1-year period after each Hb assessment. The association between Hb levels and risk of new EOD was estimated using multivariable generalized estimating equations. Results: A total of 16,043 unique patients with SCD contributed 44,913 observations. Adjusted odds of any EOD during the 1-year follow-up were significantly lower with higher Hb level. Risk reductions with higher Hb levels for chronic kidney disease, pulmonary hypertension, and leg ulcer were comparable. The risk of new EOD was significantly lower among adolescent and adult patients with higher Hb levels. Conclusions: In patients with SCD, higher Hb levels are associated with a reduced risk of developing EOD. Therapeutic strategies that result in higher Hb levels may offer clinical and economic value for patients with SCD. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

Unexplained anemia of aging: Etiology, health consequences, and diagnostic criteria.

BACKGROUND: Up to 15% of people aged 60 and over are anemic, and the prevalence of anemia increases with age. In older men and women, anemia is associated with increases in the risk of death and all-cause hospitalization, poor functional capacity, quality of life, and depression. METHODS AND RESULTS: We reviewed the literature describing anemia in aging populations, focusing on the specific diagnostic criteria of anemia and potential causes in older men and women. Even after extensive etiologic workup that involves careful medical history, physical examination, laboratory measurements, and additional studies such as bone marrow biopsy, anemia of aging is unexplained in up to 40% of older patients with anemia. As a result, treatment options remain limited. CONCLUSIONS: The prevalence of unexplained anemia of aging (UAA; also called unexplained anemia of the elderly, UAE), its deleterious impacts on health, physical function, and quality of life, and the lack of effective treatment or therapy guidelines represent a compelling unmet clinical need. In this review and consensus document, we discuss the scope of the problem, possible causes of UAA, diagnostic criteria, and potential treatment options. Because even mild anemia is strongly linked to poor clinical outcomes, it should receive clinical attention rather than simply being considered a normal part of aging.

Remote Home Monitoring of Patients With Cancer During the COVID Pandemic: A Pilot Study.

PURPOSE: The COVID-19 pandemic has posed significant challenges in the care of patients with cancer, including how to manage outpatients who are COVID-positive but do not require hospitalization. We explored the use of a remote patient monitoring (RPM) program to care for such outpatients. METHODS: Consecutive patients who were tested for COVID-19 because of symptom onset but were clinically stable were offered enrollment into a pilot RPM program. Patients were provided equipment for vital sign measurements and a computer tablet to enter results three times per day. The results were monitored centrally by clinical staff. The goal was to closely monitor patients and escalate care as warranted. RESULTS: Between March and June of 2020, 29 patients were approached and 26 were enrolled. The mean age was 57 years old (range, 30-88), 14 were women, and patients remained in the program for an average of 16 days (range, 2-63). Twenty-four patients (83%) were on active anticancer therapy. During that time period, only one patient was admitted to the hospital for worsening respiratory symptoms. The percentage of days during which at least one set of data and all three sets of data were entered was 97.2% and 65.7%, respectively. There was no association between the demographic factors of age, sex, or the reason for being monitored with the level of engagement (P > .05). CONCLUSION: In this pilot study, patients with cancer were readily enrolled in a remote home monitoring program. Monitoring was feasible, and there was a high rate of engagement with the program. The role of RPM should be further tested as the COVID pandemic continues.

Unexplained Anemia in the Elderly.

The prevalence of anemia increases with advancing age, and despite thorough investigation, approximately one-third will be classified as "unexplained." Unexplained anemia (UA) is typically hypoproliferative, normocytic, and with low reticulocyte count. Serum erythropoietin levels are lower than expected for degree of anemia. Chronic inflammation, low testosterone levels, malnutrition, and possibly nascent myelodysplasia are variably contributing factors. No clearly established beneficial treatment strategy has been established, but the association of UA with a wide range of adverse outcomes, including impaired quality of life, physical function, and mortality, is sufficiently compelling to justify expanding clinical research focused on basic and clinical aspects.

A cell transportation solution that preserves live circulating tumor cells in patient blood samples.

BACKGROUND: Circulating tumor cells (CTCs) are typically collected into CellSave fixative tubes, which kills the cells, but preserves their morphology. Currently, the clinical utility of CTCs is mostly limited to their enumeration. More detailed investigation of CTC biology can be performed on live cells, but obtaining live CTCs is technically challenging, requiring blood collection into biocompatible solutions and rapid isolation which limits transportation options. To overcome the instability of CTCs, we formulated a sugar based cell transportation solution (SBTS) that stabilizes cell viability at ambient temperature. In this study we examined the long term viability of human cancer cell lines, primary cells and CTCs in human blood samples in the SBTS for transportation purposes. METHODS: Four cell lines, 5 primary human cells and purified human PBMCs were tested to determine the viability of cells stored in the transportation solution at ambient temperature for up to 7 days. We then demonstrated viability of MCF-7 cells spiked into normal blood with SBTS and stored for up to 7 days. A pilot study was then run on blood samples from 3 patients with metastatic malignancies stored with or without SBTS for 6 days. CTCs were then purified by Ficoll separation/microfilter isolation and identified using CTC markers. Cell viability was assessed using trypan blue or CellTracker™ live cell stain. RESULTS: Our results suggest that primary/immortalized cell lines stored in SBTS remain ~90% viable for > 72 h. Further, MCF-7 cells spiked into whole blood remain viable when stored with SBTS for up to 7 days. Finally, live CTCs were isolated from cancer patient blood samples kept in SBTS at ambient temperature for 6 days. No CTCs were isolated from blood samples stored without SBTS. CONCLUSIONS: In this proof of principle pilot study we show that viability of cell lines is preserved for days using SBTS. Further, this solution can be used to store patient derived blood samples for eventual isolation of viable CTCs after days of storage. Therefore, we suggest an effective and economical transportation of cancer patient blood samples containing live CTCs can be achieved.

A prospective randomized wait list control trial of intravenous iron sucrose in older adults with unexplained anemia and serum ferritin 20-200 ng/mL.

Anemia is common in older persons and is associated with substantial morbidity and mortality. One third of anemic older adults have unexplained anemia of the elderly (UAE). We carried out a randomized, wait list control trial in outpatients with UAE and serum ferritin levels between 20 and 200 ng/mL. Intravenous iron sucrose was given as a 200-mg weekly dose for 5 weeks either immediately after enrollment (immediate intervention group) or following a 12-week wait list period (wait list control group). The primary outcome measure was changed in 6-minute walk test (6MWT) distances from baseline to 12 weeks between the two groups. Hematologic, physical, cognitive, and quality of life parameters were also assessed. The study was terminated early after 19 subjects enrolled. The distance walked in the 6MWT increased a mean 8.05±55.48 m in the immediate intervention group and decreased a mean 11.45±49.46 m in the wait list control group (p=0.443). The hemoglobin increased a mean 0.39±0.46 g/dL in the immediate intervention group and declined a mean 0.39±0.85 g/dL in the wait list control group (p=0.026). Thus, a subgroup of adults with UAE may respond to intravenous iron. Enrollment of subjects into this type of study remains challenging.

Iron deficiency anemia--bridging the knowledge and practice gap.

Despite its high prevalence, anemia often does not receive proper clinical attention, and detection, evaluation, and management of iron deficiency anemia and iron-restricted erythropoiesis can possibly be an unmet medical need. A multidisciplinary panel of clinicians with expertise in anemia management convened and reviewed recent published data on prevalence, etiology, and health implications of anemia as well as current therapeutic options and available guidelines on management of anemia across various patient populations and made recommendations on the detection, diagnostic approach, and management of anemia. The available evidence confirms that the prevalence of anemia is high across all populations, especially in hospitalized patients. Anemia is associated with worse clinical outcomes including longer length of hospital stay, diminished quality of life, and increased risk of morbidity and mortality, and it is a modifiable risk factor of allogeneic blood transfusion with its own inherent risks. Iron deficiency is usually present in anemic patients. An algorithm for detection and management of anemia was discussed, which incorporated iron study (with primary emphasis on transferrin saturation), serum creatinine and glomerular filtration rate, and vitamin B12 and folic acid measurements. Management strategies included iron therapy (oral or intravenous), erythropoiesis-stimulating agents, and referral as needed.

Multiple myeloma in the very old: an IASIA conference report.

Multiple myeloma (MM) in patients aged greater than 80 years poses an increasingly common challenge for oncology providers. A multidisciplinary workshop was held in which MM-focused hematologists/oncologists, geriatricians, and associated health-care team members discussed the state of research for MM therapy, as well as themes from geriatric medicine that pertain directly to this patient population. A summary statement of our discussions is presented here, in which we highlight several topics. MM disproportionately affects senior adults, and demographic trends indicate that this trend will accelerate. Complex issues impact cancer in seniors, and although factors such as social environment, comorbidities, and frailty have been well characterized in nononcological geriatric medicine, these themes have been inadequately explored in cancers such as MM, despite their clear relevance to this field. Therapeutically, novel agents have improved survival for MM patients of all ages, but less so for seniors than younger patients for a variety of reasons. Lastly, both MM- and treatment-related symptoms and toxicities require special attention in senior adults. Existing research provides limited insight into how best to manage these often complex patients, who are often not reflected in typical clinical trial populations. We hence offer suggestions for clinical trials that address knowledge gaps in how to manage very old and/or frail patients with MM, given the complicated issues that often surround this patient population.

The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men.

Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation. Potential limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one participant. Conclusion Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort.

Is cancer incidence decreased in the frail elderly? Evidence from a prospective cohort study.

OBJECTIVES: Lower rates of cancer in the oldest old and in nursing home populations may reflect the increasing prevalence of frailty and a diminished capacity to sustain cancer cell growth and proliferation. This study aimed to determine cancer incidence in the frail relative to non-frail community resident older adults. MATERIALS AND METHODS: Data from 3969 participants free of diagnosed cancer at the sixth follow-up from three sites of the Established Populations for Epidemiologic Studies of the Elderly (EPESE), a population-based cohort study. Frailty status was determined from physical performance testing and self reported dependency in activities of daily living. Cancer incidence over the four subsequent years was identified through linkage with Medicare claims data. Logistic regression was used to estimate the odds of cancer incidence with respect to frailty status in multiple models with progressive adjustment for covariates. RESULTS: Of the 3969 participants, 1340 (33.8%) were identified as frail. Cancer incidence at 4years was lower in frail participants overall (OR 0.64; 95% CI 0.46-0.89) and frail men in particular (OR 0.54; 95% CI 0.33-0.87). Incidence was lower in women (3.7%) than in men (8.8%), but was not lower in frail women compared with non-frail women (OR 0.77; 95% CI 0.48-1.23). CONCLUSION: Frailty status was associated with decreased cancer incidence, particularly in men, and suggests that mechanisms related to the pathogenesis of frailty may also play a role in inhibiting tumorigenesis. Why this would be more apparent in men than women remains to be clarified.

Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades.

BACKGROUND: Acute myeloid leukemia (AML) is the common form of acute leukemia in adults, accounting for over 80% of all acute leukemias in individuals aged >18 years. Overall 5-year survival remains poor in older AML patients; it is <5% in patients aged >65 years. In this study, the authors examined whether survival has improved for subsets of geriatric AML patients over 3 successive decades. METHODS: Surveillance, Epidemiology and End Results (SEER) data were used to determine trends in relative survival by age among 19,000 patients with AML over 3 successive decades (1977-1986, 1987-1996, and 1997-2006). Relative survival rates (RRs) with 95% confidence intervals (CIs) were calculated as measures of survival. RESULTS: Overall, the RRs increased for each successive decade (1977-1986, 1987-1996, and 1997-2006) in patients ages 65 to 74 years, with improvements in 12-month survival from 20%, to 25%, to 30%, respectively. Findings were similar for 24-month, 36-month, 48-month, and 60-month survival. However, survival rates did not improve in patients aged ≥75 years. The oldest old patients (aged ≥85 years) had the lowest survival rates, with no apparent improvement. CONCLUSIONS: This analysis of a large data set demonstrated that, although overall survival remained unsatisfactory among older patients, it improved in the younger old (ages 65-74 years). Survival of older old AML patients has not been favorably impacted by available AML therapies or supportive care, and intervention in this age group is best undertaken on a clinical trial.

Association of the red cell distribution width with red blood cell deformability.

The red cell distribution width (RDW) is a component of the automated complete blood count (CBC) that quantifies heterogeneity in the size of circulating erythrocytes. Higher RDW values reflect greater variation in red blood cell (RBC) volumes and are associated with increased risk for cardiovascular disease (CVD) events. The mechanisms underlying this association are unclear, but RBC deformability might play a role. CBCs were assessed in 293 adults who were clinically examined. RBC deformability (expressed as the elongation index) was measured using a microfluidic slit-flow ektacytometer. Multivariate regression analysis identified a clear threshold effect whereby RDW values above 14.0% were significantly associated with decreased RBC deformability (ß = -0.24; p = 0.003). This association was stronger after excluding anemic participants (ß = -0.40; p = 0.008). Greater variation in RBC volumes (increased RDW) is associated with decreased RBC deformability, which can impair blood flow through the microcirculation. The resultant hypoxia may help to explain the previously reported increased risk for CVD events associated with elevated RDW.

Superior vena cava syndrome as a presentation of metastatic prostate cancer.

Superior vena cava (SVC) syndrome is an uncommon complication of malignant disease caused by the obstruction of venous blood flow in the SVC. When present, a diagnosis of lung cancer or lymphoma will be made in approximately 95% of cases. Although other malignant diseases are occasionally associated with SVC, its occurrence in patients with prostate cancer is rare. We present a case of a patient presenting with SVC obstruction who was subsequently diagnosed with prostate adenocarcinoma. The patient has been successfully treated with GnRH agonist. This case reflects the importance of a full clinical assessment and pathological confirmation of suspected tumour prior to treatment.

Long-term survival of older breast cancer patients: population-based estimates over three decades.

Significant progress has been made in the treatment of breast cancer. However, treatment effect on survival in older patients, particularly the "oldest old" (85+ years), with breast cancer is not clear. Data from the Surveillance, Epidemiology, and End Results databases were used to determine relative survival of older patients with breast cancer for up to 9 years following diagnosis. We compared trends in survival and stage distribution in the years 1977-1986, 1987-1996, and 1997-2006 in patients from 65 to 74, 75 to 84, and 85+ years of age. Between 1977-1986 and 1997-2006, 1 year survival increased from 94.9 to 97.9 %, 93.6 to 96.7 %, and 88.5 to 93.5 % in the 65-74, 75-84, and 85+ age groups, respectively. Survival gains increased with each year in all three age groups with the largest improvement seen at 9 years of follow-up. Although the "oldest old" had the lowest survival rates, improvement in survival was greatest in this age group with greater than 20 % increase in survival at 9 years. There was an increased diagnosis of localized breast cancer and decrease in regional disease in all age groups over the three decades. In conclusion, relative survival for older patients has increased considerably in the interval between 1977 and 2006, with the largest improvement seen in those 85 years and older. These results likely indicate that the benefit from advances in therapy and supportive care also extends to older patients with breast cancer, including the 'oldest old', but the impact of early diagnosis on survival requires further clarification.