Previous Diagnosis Research Articles

Serological Survey of Severe Acute Respiratory Syndrome Coronavirus -2 (Sars-Cov-2) among Frontline Health Workers in Northwest Nigeria

Background: Serological testing of SARS-CoV-2-specific IgG/IgM antibodies is an important complement to Real Time-PCR (RT-PCR) for surveillance and outbreak investigations. The study therefore aimed to assess the serological survey of SARS-COV-2 among frontline health workers using specific IgG/IgM antibodies.
 Methods: The study was a cross-sectional design. A self-administered questionnaire was used to obtain biodata. Rapid diagnostic test kits were used for the study in which samples reacted with COVID-19 antigen-coated particles in the test cassette and the complex formed produced readable bands indicating the presence of SARS-COV19 in the tested subject. Data obtained were analyzed using Stata v15.
 Results: The prevalence of SARS-CoV-2 among the study sample was 39.0% and 14.9% for IgG and IgM respectively. Prevalence was highest in the outpatient department (IgG; 70.0%, IgM; 17.1%). IgG positivity was observed more among doctors while positivity for IgG was seen in 78.6% of persons with previous diagnoses. IgM was significantly associated with contact with patients having shortness of breath, p-value < 0.05.
 Conclusion: This study demonstrated a high level of SARS-COV19 IgG indicating past infection and IgM suggesting recent exposure or ongoing infection among this group of workers compared to others within the hospital settings. The role of serological testing cannot be over-emphasized in the periodic screening and prompt treatment of health workers before they manifest symptoms or become capable of spreading the disease to innocent patients and or co-health workers.

Socio-Demographic and Disability Disparities in Stroke by Citizenship Status: A Cross-Sectional Analysis.

This study aims to assess relationships between previous stroke diagnosis and demographic or disability status variables, stratified by U.S. citizenship status. The2019 and 2021 National Health Interview Survey data were analyzed for both descriptive statistics and logistic regression models. Age, sex, income level, race/ethnicity, health insurance status, and indicators of disability common after stroke were predictor variables of interest. For each disability predictor variable, higher odds of having stroke were seen regardless of citizenship status, except for the 'difficulty remembering' variable. For U.S. citizens, increasing age corresponded with higher odds of stroke diagnosis. For noncitizens, odds ratios decreased from 40.3 (95% CI 38.88-41.82) for the 40-65 age group to 29.6 (95% CI 28.38-30.77) in the 80 + group, when compared with the 18-39 age reference group. Female noncitizens had higher odds of stroke, while male citizens had higher odds. Non-Hispanic Black citizens had higher odds of stroke, while the other racial/ethnic groups had higher odds for noncitizens. The results indicated the existence of several socio-demographic disparities in stroke. Notably, noncitizens experienced stroke at a younger age and reported more severe disability outcomes after stroke diagnosis than citizens.

Prevalence of Highly Sensitive Personality and Its Relationship With Depression, and Anxiety in the Saudi General Population.

Background Highly sensitive personality (HSP) occurs in those who experience stronger processing of emotions and responses to both internal and external stimuli; this, in turn, could cause persons with highly sensitive personalities tosuffer from affective disorders such as depression and anxiety at higher rates. This study aimed to measure the prevalence ofhighly sensitive personality and its relationship with depressionand anxiety among the Saudi general population. Subject and methods This cross-sectional study was conducted among the general population in Saudi Arabia. A self-administered questionnaire was sent to the target population using an online survey. The questionnaire includes sociodemographic data (i.e., age, gender, marital status, etc.), the Highly Sensitive PersonScaleto measure the degree ofsensitivity, and the Hospital Anxiety and Depression Scale (HADS) to measure anxiety and depression. Results Of the 438 participants, 72.6% were females, and 48.9% were aged between 18 to 25 years. The prevalence of HSP in this study was 29%. Abnormal levels of anxiety and depression were found in 29.5% and 19.9%, respectively. Significant relationships were observed between HSP in terms of anxiety (p<0.001) and depression (p=0.001). It is interesting to note that a previous diagnosis of mental disorder was identified as a significant risk factor for HSP, anxiety, and depression. Conclusion There was ahigh prevalence of HSP in our population, which was significantly associated with anxiety and depression. Further, female participants were more likely to exhibit HSP and anxiety but not depression. These findings highlight the importance of prevention programs intended for highly sensitive persons with associated mental conditions.

Abstract B023: Monoclonal gammopathy of undetermined significance and multiple myeloma survival among Hispanics living in Puerto Rico

Abstract Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a pre-malignant condition that may progress to multiple myeloma (MM). The aim of this study was to investigate the effect of previous MGUS diagnosis on MM survival. Methods: Data from the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database were analyzed. The study included incident cases of MM diagnosed between 2010 and 2016. Patients with a previous MGUS diagnosis were identified through a claims-based algorithm. Competing-risk modeling was used to estimate the impact of previous MGUS on MM survival, adjusting for sex, age, comorbidity index, and insurance. The results were stratified by sociodemographic characteristics. Results: Of the 1,205 patients diagnosed with MM, 9.7% (n=117) had a previous diagnosis of MGUS. Patients with a previous MGUS diagnosis were found to be older, with a higher comorbidity index, and had Medicare compared to those without a previous MGUS diagnosis. Additionally, these patients were less likely to die from MM (SHR: 0.48, 95%CI=0.33-0.71) than those without a previous MGUS diagnosis. The magnitude of the association between MGUS and MM mortality varied by sociodemographic characteristics. For example, patients between 40-69 years with a previous MGUS diagnosis were less likely to die from MM (SHR:0.23, 95%CI=0.09-0.60) than those without MGUS. Patients with MGUS and ≤1 comorbidity index were also less likely to die from MM (SHR:0.31, 95%CI=0.18-0.55) than those without MGUS with the same comorbidity index. Males with MGUS were less likely to die from MM (SHR:0.41, 95%CI=0.22-0.73), but the association was weaker among females. Patients with MGUS and Medicare were less likely to die from MM (SHR:0.43, 95%CI=0.25-0.74) than those without MGUS who also had Medicare. No significant association was found between MGUS and MM mortality among patients with other insurance types, other age groups, and other comorbidities index. Conclusion: Findings show that males, younger adults, and those with low comorbidity may benefit from a prior MGUS diagnosis, indicating that patients with a previous MGUS diagnosis may have improved survival due to earlier access to more effective treatments for MM. Further research is necessary to gain a comprehensive understanding of the underlying mechanisms. Citation Format: Maira Castañeda-Avila, Tonatiuh Suárez-Ramos, Carlos R. Torres-Cintrón, Axel Gierbolini-Bermúdez, Karen J. Ortiz-Ortiz. Monoclonal gammopathy of undetermined significance and multiple myeloma survival among Hispanics living in Puerto Rico [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B023.

Somatic PIK3CA Variants Are Associated With Eccrine Angiomatous Hamartomas

Objectives: Eccrine angiomatous hamartoma (EAH) is a rare vascular anomaly with mixed eccrine and vascular components, typically identified in children. While benign, EAH can cause significant morbidity and be difficult to treat. The aims of this case series were to identify all patients with EAH that have been seen at the Queensland Children’s Hospital and describe their phenotypic and somatic genotypic details, in an effort to contribute to the limiting understanding and literature surrounding this condition. Methods: Individuals with EAH were retrospectively identified through engagement in a multidisciplinary vascular anomaly clinic in a tertiary Australian children’s hospital. All individuals had a previous histological diagnosis of EAH. High-read-depth sequencing of a panel of 27 genes known to be associated with vascular anomalies was undertaken on affected tissue. Samples were rereviewed by a senior pathologist and geneticist for this study. Results: Five cases of EAH were identified. All were associated with 1 of 3 somatic PIK3CA variants (c.1633G&gt;A;p.Glu545Lys, c.1624G&gt;A;p.Glu542Lys, and c.3140A&gt;G;p.Histo1047Arg) in low allele fractions. These variants have previously been reported in a range of tumors and vascular anomalies, including PIK3CA-related overgrowth spectrum, but not in EAH. Conclusion: Occurrence of somatic PIK3CA variants in EAH provides evidence for a novel gene-disease association and is plausibly the cause of EAH in some individuals. This finding expands the phenotypic spectrum of PIK3CA, contributes to understanding of the pathophysiology of this rare condition, and may avail molecularly targeted therapy in the future.

P112: Valladolid Multicenter Study: Diagnostic agreement between physicians and liaison psychiatry units in an elderly population in 7 hospitals in Spain.

Objective:The objective of this study is to describe the diagnostic agreement between physicians and liaison psychiatry units (LPU) in 7 general hospitals of Spain for elderly patients and to analyze possible factors related to it.Methods:This is an observational., cross-sectional, multicenter study. We obtained data from a sample of 165 patients (≥65 years) admitted to 7 general hospitals in Spain referred from different departments to each liaison psychiatry unit. Data was collected for a month and a half period. Psychiatric evaluations were performed while the patients were on wards.Results:We obtained a sample of 165 patients (78 women, 88 men) with a mean age of 76,03 years old (42.10% &lt;75 years, 57,83% ≥ 75 years). Most of them were married and they lived accompanied (67,27%). Only 5,45% lived in a nursing home.In 55.15% the main reason to referral was anxiety/depression symptoms. 42,42% had no psychiatry medical background. After LPU visit a new diagnosis was done in 56.96%. Main diagnoses were adjustments disorders (26,66%), delirium (20,6%) and no psychiatric pathology (14,54%)Cohen’s kappa statistics were used to estimate the agreement between the diagnoses made by LPU and the diagnoses considered by the referring doctors. We obtained a moderate global agreement (kappa= 0,4971) between observers (0,424 for &lt;75 years, 0,557 for ≥65 years) Moderate agreement was found for alcohol or substance abuse (kappa= 0,41) and low agreement was found for affective disorders (kappa= 0,3278) and delirium/ psychological and behavioral symptoms in dementia (Kappa= 0,2341).We analyzed factors which might affect de agreement between physicians and LPU such is group of age, functional impairment, comorbidity by Charlson index and previous diagnosis of dementia.Conclusions:Further longitudinal studies might help in the future to analyze the factors related to agreement between doctors and might help to establish educational programs

P152: Early detection and evolution of Mild Behavioral Impairment in a sample of people with subjective cognitive complaints

Objective:Mild behavioral impairment (MBI) is a validated diagnostic entity, that describes the emergence of later life neuropsychiatric symptoms (NPS) in pre-dementia states. The aim of this study was to estimate the prevalence of MBI in people with subjective cognitive complains (SCCs) in primary care centers and observe the evolution in a longitudinal study.Methods:Three hundred twenty-three participants belonging to the CompAS longitudinal study who attended primary care centers with SCCs and without previous diagnosis of dementia and other neurological or psychiatric disturbances underwent clinical, neurological, and neuropsychological examinations at baseline and at two follow-up times (around 24 and 60 moths). At each evaluation point participants were diagnosed as Cognitively Unimpaired (UC), Mild Cognitive Impairment (MCI) and SDC; at the follow-up assessments dementia was diagnosed as well. Diagnosis of MBI was made via a series of semistructured independent interviews with patients and relatives in accordance with the ISTAART-AA criteria and using the Spanish MBI-C cut-off point (Mallo et al, 2019). Frequencies of participants diagnosed in each category were obtained and evolution of the MBI along the follow-up evaluations was studied.Results:MBI diagnosis prevalence was 22.9% at baseline corresponding to 74 individuals of which at 24 months follow-up were MBI stable 31.1%, 14.9% evolved to MCI, 1.3% to dementia and 40% to CU, (attrition 12.2%). At 60 months follow-up, from the 23 individuals with MBI, 6 remained stable (26.1%), 6 (21.1%) evolved to MCI, 2 (8.7%) to dementia, 3 (13%) to CU, (attrition 26.1%) (Figure 1).Conclusions:Results indicated that almost a quarter of individuals attending primary care centers with SCCs without previous diagnosis of dementia or psychiatric disorders are MBI. An important part of them evolve to UC or MCI, and only a minority progress to dementia. More studies are needed to analyze the cognitive, personal, and biological factors that determine this evolution.

Evaluating the Association Between Sociodemographic and Health Variables With Baseline Concussion Testing in Young Athletes

Background: Baseline concussion testing can be helpful to perform when providing concussion care for young athletes. To appropriately interpret these data, it is important to understand how certain factors may affect concussion testing. Purpose: To examine the relationship of sociodemographic and health variables with baseline concussion testing in young athletes. Study Design: Cross-sectional study; Level of evidence, 3. Methods: High school and middle school athletes competing in sports or positions at high risk for concussion (football, soccer, ice hockey, wrestling, lacrosse, and pitchers/catchers in baseball/softball) during the 2020-2021 or 2021-2022 academic years completed annual baseline concussion testing and were included in the study. Baseline data included self-reported demographic and medical information, a graded symptom checklist, the Standardized Assessment of Concussion, and the King-Devick test. A validated measure, HOUSES (HOUsing-based index of SocioEconomic Status), was used to determine participants’ socioeconomic status (SES) by linking personal address information to publicly available property data. Multivariable linear regression models were fit to analyze the relationship of concussion baseline testing to sociodemographic and health variables. Results: Among the eligible 2747 athletes (mean age, 15.4 ± 1.5 years; 73.6% male), the mean Standardized Assessment of Concussion score was 26.7 ± 2.0 and the mean best King-Devick test time was 50.3 ± 10.1 seconds. Higher baseline symptom severity scores were related to lower SES ( P = .002). A lower (ie, poorer) mean Standardized Assessment of Concussion score was significantly associated with the following in the multivariable model: male sex ( P &lt; .001), younger age ( P &lt; .001), Black/African American race ( P = .029), Hispanic ethnicity ( P = .016), previous diagnosis of learning disorder or attention-deficit hyperactivity disorder ( P &lt; .001), and lower SES ( P = .003). A higher (ie, poorer) mean King-Devick test time was related to younger age, previous diagnosis of a learning disorder or attention-deficit hyperactivity disorder, and lower SES (all P &lt; .001). Conclusion: Baseline concussion testing was found to be associated with certain sociodemographic variables and underlying health conditions in high school and middle school athletes.

Lung transplantation for emphysema: only emphysema or something else?

Some studies have reviewed lung explants histology to determine the frequency of pretransplant non-identified neoplasms or explore its diagnostic correlation with a previous diagnosis of interstitial lung disease (ILD). This study aims to review the histopathology of explants from patients who underwent lung transplantation (LT). A retrospective, single-center study that included patients who underwent LT for emphysema between 01 January 2011 and 31 October 2021. The control group was composed of patients with lung cancer who underwent a lung resection between 01 November 2011 and 31 December 2019 and had a previous diagnosis of chronic obstructive pulmonary disease (COPD) prior to lung resection surgery. A systematic review was performed of histological findings to compare the frequency of additional histological diagnoses. The study sample included 160 patients (43.8%) who received a lung transplant for emphysema and 205 patients with COPD and lung cancer treated surgically. Although the patients in the cancer group were significantly older and had more comorbidities and higher cumulative tobacco consumption, transplant recipients received an additional significative histologic diagnosis more frequently (58.1% vs. 12.7%; P<0.001) including ILD, pneumoconiosis and others. Significant additional histological findings were more frequent in the group of lung transplant recipients with emphysema. Notably, these findings were not explained by tobacco use, and they were significantly more frequent in transplant recipients than in patients with a previous diagnosis of COPD and higher cumulative tobacco consumption but with a better respiratory functional status.

Myelomatous Ascitis, a Rare Presenting Symptom of Multiple Myeloma

Abstract Introduction/Objective In 2022, plasma cell neoplasms accounted for approximately 1.8% of all new cancers in the United States with an estimated 34,470 new cases of multiple myeloma. Diagnosis is often straight forward in ~80% of cases by performing serum protein electrophoresis (SPEP), serum immunofixation (SIFE), and/or urine immunofixation (UIFE) with M-spike quantification. The diagnostic challange is in the remainder of asymptomatic myeloma cases (~20%) which are found incidentally. Specialized laboratory technicians are often the first step in identifying plasma cells in body fluids and/or peripheral blood smears. These incidental findings on routine labs, paired with the keen eye of a specialist, are one of the first steps in early detection of multiple myeloma. Methods/Case Report A 62 year-old male, originally from Cambodia, presented to an outside hospital emergency department with abdominal distention and pain. His past medical history was significant for dialysis-dependent end- stage renal disease and insulin-dependent diabetes mellitus type 2. Abdominal CT showed ascites with no other diagnostic findings. Cardiac, renal and hepatic etiologies of ascites were ruled out. Body fluid analysis of the ascites in the Clinical Pathology laboratory revealed numerous plasma cells. Cytologic examination, after consultation with Clinical Pathology, also revealed numerous plasma cells. Subsequent SPEP and SIFE disclosed an IgA lambda monoclonal protein. A diagnosis of multiple myeloma was confirmed by bone marrow biopsy with FISH studies. Results showed several high-risk abnormalities including translocations of 4::14, 14::16, and 14::20, denoting a “triple hit” multiple myeloma. Results (if a Case Study enter NA) NA Conclusion Plasmacytosis in ascites is an extremely rare initial presentation for multiple myeloma. With only a few cases reported in the literature, many technicians and pathologists might easily overlook plasma cells on routine cytology, especially with normal imaging and no previous diagnosis of myeloma. In this case, flagged peritoneal fluid by a skilled medical laboratory technician was key to making a diagnosis. Without any signs of a plasmacytoma or lytic bone lesions on imaging, a normal CBC with non-specific labs, and an unsuspecting surgical pathology report, multiple myeloma was not on the differential. Fast interdepartmental consultation, communication, and teamwork between surgical pathology and clinical pathology, lead to a rapid diagnosis and prompt treatment of this patient.

Focal Plasmacytoid and Fibrotic Hepatic Lesion In An Autopsy Examination Of A Patient With Multiple Myeloma

Abstract Introduction/Objective Multiple Myeloma (MM) is a plasma cell neoplasm mainly affecting the bone marrow. Common sites of extramedullary dissemination are skin, liver, kidneys, and the central nervous system. Though diffuse plasma cell infiltration of the liver has been described in autopsy literature in about 50% of patients with multiple myeloma, it is usually not associated with focal infiltration. Rare cases of plasma cell infiltration leading to non-obstructive cholestasis and acute hepatic failure have been described. Methods/Case Report We hereby present a case of 54-year-old decedent male with past medical history of obesity, hypertension, and diabetes mellitus who presented to the emergency department with complains of productive cough, dyspnea, vomiting and back discomfort. Labs showed leukocytosis, thrombocytopenia and hypercalcemia. Additionally, there was an increase in lactate and serum monoclonal protein levels and derangements in renal and liver function tests. Skeletal bone survey showed a 1.4 cm well-circumscribed lucent lesion within the distal third of the left clavicle and in the calvarium which raised concern for multiple myeloma and tumor lysis syndrome. During the hospital course, the patient’s overall clinical condition declined rapidly, and he passed away on the third day of admission. During the autopsy examination, the patient’s bone marrow revealed diffuse infiltration of plasma cells confirming multiple myeloma. In addition, the histopathological examination of the liver revealed focal plasmacytoid fibrosis, moderate periportal inflammation with plasma cell infiltration and microsteatosis. Immunohistochemical stains with CD138, MUM-1, ISH kappa and lambda and trichrome highlighted the focal plasma cell infiltration and fibrosis in the liver, respectively. Results (if a Case Study enter NA) NA Conclusion Our case shows the importance of utilizing histopathological and immunohistochemical examination in confirming the diagnosis of multiple myeloma, specifically in the autopsy cases where there is no previous diagnosis of multiple myeloma. In addition, it highlights the awareness of rare focal plasmacytoid fibrosis and infiltration as an extramedullary presentation of multiple myeloma.

Healthcare Resource Utilization and Costs Among Newly Diagnosed and Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients: A Retrospective Cohort Study Using Contemporary US Claims

Introduction: Prognosis for acute myeloid leukemia (AML) patients is generally poor, with rapid progression and high probability of relapse. AML has previously been associated with high healthcare resource utilization (HRU). Changes in the AML treatment landscape may have impacts on the economic burden of AML: since 2017, seven new systemic therapies have been approved for various AML patient populations, including those unfit for intensive therapy. The frequency of hematopoietic stem cell transplantation (HSCT) has also increased over this period. This retrospective cohort study aims to characterize first-line (1L) and second-line (2L) healthcare resource utilization (HRU) and costs in newly diagnosed (ND) and relapsed/refractory (R/R) AML patients, in the context of newly available AML treatments from 2017-2022. Methods: A large US administrative claims database (Optum) was used to identify ND AML patients between January 1, 2016, and August 31, 2022. The “ND index date” was defined as the first date a non-R/R AML diagnosis code was observed. To confirm that the initial AML diagnosis represented a true case of AML, ≥2 subsequent AML diagnoses within 60 days post-index were required. A washout period of 12 months was used to confirm no previous AML diagnosis. ND patients were required to have continuous enrollment from 1 year prior to the index until at least 30 days after the index date or death, whichever was earlier. A subgroup of R/R patients was then identified: all ND cohort members who 1) had an R/R AML diagnosis code, 2) had continuous enrollment between ND and at least 30 days after the R/R index date, and 3) did not receive 1L HSCT after the ND index date were eligible for inclusion. In this subgroup, the “R/R index date” was defined as the first date an R/R AML diagnosis code was observed. Patient per-patient-per-month (PPPM) HRU and costs were followed through the earliest of HSCT, clinical trial enrollment, death, loss of enrollment, end of data availability (September 30, 2022),or R/R diagnosis (for ND patients only). All results were reported descriptively by line of therapy and treatment received (HSCT vs. non-HSCT). Subgroup analyses were performed by age category. Results: We identified 3,145 ND and 644 R/R AML patients who received treatment over the study period. 3.4% of all treated ND patients received HSCT in 1L (n=107), while 19% of all treated R/R patients received HSCT in 2L (n=122). HSCT patients were younger and healthier than non-HSCT patients, reflecting selection into HSCT treatment by underlying patient characteristics (for ND patients, mean age at diagnosis 71.4 vs. 61.1; Mean Charlson Comorbidity Index (CCI) score 2.8 vs. 2.0; unfit for intensive chemotherapy 69% vs. 36%, Table 1). Patients receiving HSCT in 1L and 2L appeared to have more outpatient encounters (ND: mean 7.4 vs. 5.6; RR: mean 7.5 vs. 6.1, PPPM) than those not receiving HSCT. Number of inpatient days appeared somewhat higher among transplant recipients in 1L, but were similar to non-transplant recipients in 2L ( Table 2). While baseline pre-AML costs increased with age in 1L ($4,478 among patients 75 or older, $3,508 among patients younger than 65, PPPM), 1L follow-up costs were highest in the youngest cohort and lowest in the oldest cohort ($74,083 vs. $40,547, PPPM). Treatment-associated PPPM costs (medical + pharmacy) appeared higher in 1L vs. 2L ($54,457 vs. $48,595). When stratified by transplant status, total PPPM costs for patients receiving HSCT in 1L were higher than for those not receiving HSCT ($74,538 vs. $53,751), driven primarily by higher medical costs ($70,757 vs. $50,283). The same pattern was observed in 2L transplant vs. non-transplant patients ($56,380 vs. $46,979 total costs, $51,712 vs. $41,986 medical costs). Conclusions: The economic burden of AML for both ND and R/R patients in the context of newly available therapies remains substantial. Total costs were comparable but slightly higher for 1L therapy as compared to 2L, and significantly higher among patients receiving HSCT compared to those not receiving HSCT in both 1L and 2L. Decreasing economic burden with age was driven by lower medical costs associated with higher rates of supportive/palliative care, suggesting a lack of available active treatment options among older AML patients.

Real-World Treatment Patterns and Overall Survival Among Newly Diagnosed and Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients: A Retrospective Cohort Study Using Claims Data

Introduction: Acute myeloid leukemia (AML) is a malignant disorder of the bone marrow, characterized by abnormal clonal proliferation and differentiation arrest of myeloid progenitor cells. Prognosis is generally poor and worsens with age. While curative therapies are available, they are often unavailable to older patients and those with significant comorbidities due to high morbidity and mortality associated with intensive therapy. Since 2017, seven new systemic therapies have been approved for various AML patient populations, including those unfit for intensive therapy. This study aims to characterize first-line (1L) and second-line (2L) treatment patterns and outcomes in newly diagnosed (ND) and relapsed/refractory (R/R) AML patients, in the context of these newly available therapies. Methods: A large US administrative claims database (Optum) was used to identify ND AML patients between January 1, 2016, and August 31, 2022. The “ND index date” was defined as the first date a non-R/R AML diagnosis code was observed. To confirm that the initial AML diagnosis represented a true case of AML, ≥2 subsequent AML diagnoses within 60 days post-index were required. A washout period of 12 months was used to confirm no previous AML diagnosis. ND patients were required to have continuous enrollment from 1 year prior to the index until ≥30 days after the index date or death, whichever was earlier. A subgroup of R/R patients was then identified: all ND cohort members who 1) had an R/R AML diagnosis code, 2) had continuous enrollment between ND index date and ≥30 days after the RR index date, and 3) did not receive 1L hematopoietic stem cell transplant (HSCT) after the ND index date were eligible for inclusion. In this subgroup, the “RR index date” was defined as the first date an R/R AML diagnosis code was observed. Demographic characteristics, clinical characteristics, and treatment patterns over time were reported descriptively. Treatment regimens over time were described using the following classification: HSCT, intensive chemotherapy without targeted agents, intensive chemotherapy with targeted agents, hypomethylating agent (HMA) therapy only, other targeted therapy, Venetoclax-based therapy, unspecified/other treatment, no treatment/supportive care only. Overall survival (OS) was described using the Kaplan-Meier estimator. All analyses were stratified by line of therapy and transplant status. Results: We identified 5,135 ND AML patients and 934 R/R AML patients (ND cohort: mean age at initial AML diagnosis 73.5 years, mean follow-up time 6.1 months). ND patients receiving transplant in 1L tended to be younger and had fewer comorbidities than those not receiving transplant ( Table 1). Over the entire study period, 61% of ND patients and 69% of R/R patients received some treatment for AML; older patients were more likely to receive supportive care only. In 1L, Venetoclax-based and intensive chemotherapy without targeted agents were the most common treatment regimens (21% and 17% of all ND patients). In 2L, Venetoclax-based and HMA-only therapies were most common (17% and 16% of all R/R patients). Increases in the use of novel therapies (Venetoclax, intensive chemotherapy with targeted agents, or other targeted therapies) were observed in both 1L and 2L over the study period ( Figure 1). 1-year OS among ND patients was 32% in non-transplant recipients, and 84% in transplant recipients; among R/R patients, 1-year OS from RR index date was 21% in non-transplant recipients and 81% in transplant recipients. Conclusions: The findings from the present study indicate substantial disease burden and ongoing unmet need among ND and R/R AML patients in the USA. While treatment patterns for AML have changed significantly following the advent of novel therapies (with 41% of 1L patients and 31% of 2L patients being treated with novel therapies in 2022), OS remained low. Notably, around 1/3 of patients with RR AML did not receive active treatment; these patients tended to be older and were more frail. Increasing off-label use of Venetoclax in 2L further underscores high unmet need for patients who require more effective treatment options.

The ELEMENT-MDS Trial: A Phase 3 Randomized Study Evaluating Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent-Naive, Non-Transfusion-Dependent, Lower-Risk Myelodysplastic Syndromes

Background and Significance: Anemia is a common and debilitating symptom in patients with myelodysplastic syndromes (MDS), frequently leading to dependence on red blood cell (RBC) transfusions. Transfusion-dependent (TD) patients have worse overall survival and quality of life, and repeat transfusions are associated with complications, including iron overload. Erythropoiesis-stimulating agents (ESAs) are the standard treatment for anemia in patients with lower-risk (LR)-MDS, but many patients are ineligible for or refractory to ESAs, and responses are limited. Luspatercept, a late-stage erythroid maturation agent, is approved to treat TD patients with LR-MDS after ESA failure. In the phase 3 COMMANDS study, in ESA-naive patients with LR-MDS requiring transfusions, a significantly higher proportion of patients receiving luspatercept than epoetin alfa achieved RBC transfusion independence for ≥ 12 weeks with concurrent hemoglobin (Hb) increase ≥ 1.5 g/dL (weeks 1-24) (Platzbecker U, et al. Lancet 2023. doi: 10.1016/S0140-6736(23)00874-7). The potential of luspatercept to improve moderately severe chronic anemia and reduce RBC transfusion dependence has not yet been investigated in the majority non-transfusion-dependent (NTD) LR-MDS patient population. Preventing transfusion dependence is crucial for improving LR-MDS patient outcomes. The aim of this actively enrolling, phase 3, randomized, multicenter study is to compare the safety and efficacy of luspatercept versus epoetin alfa in reducing progression to RBC transfusion dependence in ESA-naive, NTD adult patients with anemia due to LR-MDS. Study design and methods: The ELEMENT-MDS study includes a 5-week screening period, a 96-week treatment period, an extension phase, and a post-treatment follow-up period (Figure). Target enrollment is 360 patients with anemia due to Revised International Prognostic Scoring System (IPSS-R) Very low-, Low-, or Intermediate-risk MDS. Eligible patients are ≥ 18 years of age with a confirmed MDS diagnosis, baseline serum erythropoietin (sEPO) levels ≤ 500 U/L, and symptomatic anemia defined as a score of moderate or worse on ≥ 1 Patient Global Impression of Severity (PGI-S) item (fatigue, shortness of breath, weakness, or dizziness). Participants must be RBC transfusion-independent per International Working Group 2018 criteria (no RBC transfusions within 16 weeks prior to randomization) and have baseline Hb ≤ 9.5 g/dL. Patients will be excluded if they have a del(5q) cytogenetic abnormality, unclassifiable MDS or myelodysplastic/myeloproliferative neoplasms, anemia due to reasons other than MDS, bleeding disorders, low absolute neutrophil or platelet counts, uncontrolled hypertension, previous acute myeloid leukemia diagnosis, or history of recent malignancies, among other reasons. Participants will be randomized 1:1 to receive luspatercept or epoetin alfa. Stratification factors include baseline sEPO levels, ring sideroblast status, and IPSS-R risk category. Patients will receive luspatercept once every 3 weeks at a starting dose of 1.0 mg/kg (escalation up to 1.75 mg/kg allowed) or epoetin alfa once a week at a starting dose of 450 IU/kg (escalation up to 1050 IU/kg allowed). The primary endpoint will compare the proportion of patients becoming TD (defined as requiring ≥ 3 RBC units/16 weeks) during any continuous 16-week interval in weeks 1-96. The key secondary endpoint is a Hb increase ≥ 1.5 g/dL sustained for ≥ 16 weeks during weeks 1-48. Additional secondary endpoints include time to RBC transfusion dependence, transfusion-free survival, time to achieve modified hematologic improvement-erythroid response, transfusion independence ≥ 24 weeks, and quality of life assessment. Safety endpoints include type and severity of adverse events and relationship to treatment, overall survival, and progression to high-risk MDS and acute myeloid leukemia. Summary: The results of this phase 3 study will determine the efficacy and safety of luspatercept as a therapy for ESA-naive NTD patients with LR-MDS, who have limited treatment options for anemia. The study is registered at ClinicalTrials.gov (NCT05949684) and EudraCT (2022-500430-29-00).

Pregnancy and Immune Mediated Thrombotic Thrombocytopenic Purpura (iTTP); A Descriptive Analysis from the U.S. Thrombotic Microangiopathy (USTMA) Registry

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is defined by thrombocytopenia and microangiopathic hemolytic anemia without an alternative explanation, confirmed by severely deficient ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) to &amp;lt;10%. It is caused by autoantibodies against the ADAMTS13 protease. Pregnancy can precipitate iTTP, but the diagnosis and treatment are challenging, since it is often difficult to differentiate from other TMAs associated with pregnancy The aim of this study was to describe the clinical presentation, treatment, and outcomes of pregnancy related iTTP. Methods: Data was obtained from the USTMA retrospective database, including 15 large USTMA referral centers. Patients were identified based on the diagnosis of iTTP provoked by pregnancy between 9/6/1990 and 6/18/2018. The study cohort included participants with a clinical diagnosis of iTTP, confirmed by ADAMTS13 activity &amp;lt;10% who had a pregnancy or recent delivery within 30 days of presenting with iTTP. For participants diagnosed before the ADAMTS13 assay was developed (2006), the iTTP diagnosis was based on the clinical course and absence of alternative causes. iTTP exacerbation was defined as clinical disease recurrence within 30 days of PLEX (plasma exchange) discontinuation, and clinical relapse was defined as disease recurrence after 30 days of last PLEX. Maternal and fetal outcomes were additionally collected from 7/15 sites. Results: 42 patients had 55 iTTP episodes provoked by pregnancy. Median age for patients was 29. Sixteen (38.1%) were white, 20 (47.6%) were black. The most common presenting symptoms were headache and fatigue in 11/55 (20%) episodes. Thirty nine (70.9%) episodes had a platelet count &amp;lt;30 x10 9/L, and 46 (83.6%) had laboratory findings concerning for hemolysis as evidenced by elevated lactate dehydrogenase (LDH) and/or schistocytes present on peripheral smear. Only 5 (9%) episodes presented with a creatinine &amp;gt;2 mg/dL. ADAMTS13 activity was documented in 33 (60%) episodes and was &amp;lt;10% in 30 (90.9%) (Table 1). Treatment with PLEX was described in 30 (54.5%) episodes with a median duration of 6 days (2-26 days). Further immunosuppression included prednisone in 38 (69.1%) episodes and rituximab in 11 (20%), of which 7 (63.6%) had no future exacerbations or relapses during the study period.Seventeen (40.5%) patients had a prior diagnosis of iTTP. There were 10 exacerbations in 8 patients (19%), and 34 relapses in 13 (30%) patients after the 55-pregnancy provoked iTTP episodes. Five of those relapses were triggered again by pregnancy. Pregnancy related outcomes were obtained in 16 patients. Twenty five percent (4/16) of patients had a prior history of iTTP; median time of last iTTP to current presentation was 34 months (10-108). Of 16 patients, iTTP occurred with first pregnancy in 8 patients. Of the remaining eight patients, iTTP occurred in the eleventh (n=1), ninth (n=1), sixth (n=1), fifth (n=1), fourth (n=2), and unknown (n=2) pregnancy. Only 13 of 16 patients had further pregnancy specific outcomes available (Table 2). Preeclampsia was noted in 3 patients. Seven and 1 patients, presented with iTTP within 30 days postpartum or after miscarriage, respectively. The remaining patients (n=5) developed iTTP during the antepartum period. Of these, 2 pregnancies were terminated due to iTTP (second trimester and third trimester). One of the three remaining pregnancies resulted in fetal demise at 24 weeks. The latter two patients delivered healthy infants. There were no maternal deaths in our cohort. Conclusions: This is first multicenter descriptive analysis of pregnancy related iTTP from the USTMA registry. The clinical presentation of this cohort is consistent with iTTP triggered by other causes, and the low rate of acute kidney injury is helpful in identifying iTTP from other TMAs in pregnancy. We observed that pregnancy is a risk not only for acute episodes of iTTP in first pregnancy, but also in subsequent pregnancies and in the relapse setting of those with previous diagnosis of iTTP. While there was a 20% and 30% exacerbation and relapse rate respectively, maternal mortality was not observed. Rituximab did not affect maternal mortality. Fetal mortality was affected by iTTP in the antepartum period. These findings will serve as bases of prospective USTMA study for standardize management of this population.

Late Hematologic Recovery after CPX-351 Induction Chemotherapy in AML: Predictive Disease and Patient's Factors and Their Impact on Survival

In a randomized Phase III trial, CPX-351has shown to be more effective than conventional 3+7 chemotherapy as frontline treatment for secondary or therapy-related AML. However, longer time for haematologic recovery (HR) after induction cycle (IC) was observed among CPX-351 treated patients. Later real-world evidences confirmed this observation, noting in addition that the time to HR was quite variable among different patients, as some patients showed quick recovery whereas others showed very delayed HR. However, despite the high clinical relevance, no specific factors related to a longer time to HR have been identified in CPX-351 treated patients so far.The aim of this study was to identify patients-related factors related to delayed HR and the outcome of patients showing a late HR. Data from 130patientswith newly diagnosed AML who received 1 or 2 cycles of CPX-351 were retrospectively collected. All patients received the EMA-approved dosing and schedule of CPX-351. Median age was 66 years (32-78). MDS-related cytogenetic abnormalities(CA) were found in 68 patients (52%), whereas MDS-related genetic abnormalities in absence of CA were found in 30 patients (23%). 32 patients had t-AML (24%) and 61 (47%) had a previous diagnosis of MDS. The CR+CRi rate after induction cycle was 67%. 89/130 pts received a second course of CPX-351 after IC, with CR+CRi rate of 71% after the second induction course. Among 92 pts who achieved CR/Cri, 88 were evaluable for flow cytometry-based MRD and among them 62 (71%) had reached negativity. Forty-two patients underwent allogeneic stem cell transplantation (ASCT) in first CR (32%, 46% of responding patients), with a median time to transplant of 213 days (range 52-638). Nine more patients received ASCT in second CR. After a median follow-up of 23 months (IC 95% 14.4 - 36.7), the median OS was 21 months (95% CI 17.5-25.7). In responding patients, median time to neutrophils (PMN) &amp;gt;0.5×109/L and platelet (PLT)&amp;gt;20×109/L recovery was 32 (14-54) and 31 (10-94) days, respectively. Seven patients never achieved PMN or PLT recovery even if in CRi. A total of 23 patients (18%) showed a late HR, defined as a time to PMN &amp;gt;500 recovery &amp;gt; 35 days and/or PLT&amp;gt;20.000 &amp;gt; 40 days). Only a low bone marrow cellularity at diagnosis correlated with late HR (p&amp;lt;0.05), whereas no correlation between late HR and baseline patient's characteristics (sex, age), disease characteristics at diagnosis (cytogenetic risk, AML subtypes, diagnostic qualifiers, molecular profiles) or adverse events (bleeding, FUO, sepsis) was disclosed. Most patients with late HR showed no CA (68%), 26% of patients showed int risk CA, and only two patients (9%) had high risk CA. Interestingly, patients with late HR showed very high MRD negativity rate (19/22, 86%) and, while time to allo-HSCT was significantly longer, OS was not different from what observed in patients achieving CR without late HR. In conclusions, CPX-treated patients who show a late HR are likely to be affected by AML progressing form MDS with low cellularity, having less adverse cytogenetic risk (hypoplastic/aplastic MDS). Those patients, despite the long time to HR, usually show a good response to CPX and an outcome superimposable with responding patients with normal time to HR time.

Sotagliflozin: Efficacy, Safety, and Potential Therapeutic Applications in Heart Failure.

To describe the pharmacology, clinical efficacy, and safety evidence of sotagliflozin, the first approved dual inhibitor of sodium-glucose cotransporter (SGLT) 1 and SGLT2, in heart failure (HF) management. A literature search of studies published between January 2012 and September 2023 were identified using PubMed, MEDLINE, and clinicaltrials.gov with search terms of "sotagliflozin," "Inpefa," or "LX4211." All available studies in English were considered. Studies were included if they investigated drug pharmacology, efficacy, or safety information. Two phase 3 trials of sotagliflozin, SOLOIST-WHF and SCORED, evaluated sotagliflozin compared with placebo in patients with type 2 diabetes mellitus (T2DM). SOLOIST-WHF reported a statistically decreased rate of cardiovascular and HF events with sotagliflozin (hazard ratio [HR] = 0.67, 95% CI = 0.52-0.85), while SCORED found a statistically significant decrease in incidence of cardiovascular events in patients with T2DM, chronic kidney disease (CKD), and risk factors for cardiovascular disease in patients in the sotagliflozin group (HR = 0.74, 95% CI = 0.63-0.88). While approval of sotagliflozin expands treatment options for patients with HF, the SGLT2 inhibitors, dapagliflozin and empagliflozin, have more data supporting their use in HF, additional risk reduction benefits in patients with CKD, and approval for use in T2DM. Landmark trials of sotagliflozin required a previous diagnosis of T2DM, despite the broader approved indication. Where sotagliflozin will be adopted into the treatment of HF is unclear due to the evidence and benefits of already established SGLT2 inhibitors and the need for comparison with SGLT2 inhibitors. Given the limitations of currently available evidence, including difficulty in fully interpreting the trial results due to changes in primary endpoints, not adjudicating the events, and not reaching the original power calculations, more investigation is warranted to determine the benefit of sotagliflozin compared with SGLT2 inhibitors.

A cross-sectional study in type 2 diabetes patients reveals that elevated pulse wave velocity predicts asymptomatic peripheral arterial disease associated with age and diabetes duration

BackgroundPeripheral arterial disease (PAD) reduces functional capacity and raises cardiovascular risks, but underdiagnosis is common, resulting in less comprehensive care than other cardiovascular conditions. While diabetes has long been viewed as a key risk factor for PAD, recent studies indicate that its impact is influenced by the presence of concurrent cardiovascular risk factors. The aim of this study is to elucidate the intricate relationship between the prevalence of PAD, diabetic complications, and cardiovascular risk factors among asymptomatic patients with type 2 diabetes mellitus (T2DM). MethodsNinety-one patients with T2DM and no symptoms or previous diagnosis of PAD were recruited from the outpatient diabetic clinic. Clinical data were extracted from electronic medical records, and the screening for PAD was conducted using MESI mTABLET. ResultsScreening for PAD among asymptomatic individuals with T2DM revealed that 5.49 % of patients exhibit a low ankle-brachial index (ABI). Patients who had previously experienced major adverse cardiovascular events or exhibited albuminuria displayed lower ABI values. Furthermore, a striking 45.05 % of the participants displayed an abnormally high carotid-femoral pulse wave velocity (cfPWV) value, with elevated PWV values correlating with advanced age and longer diabetes duration. ConclusionsThe prevalence of elevated cfPWV is more pronounced than that of decreased ABI in T2DM patients with asymptomatic PAD and is associated with older age and longer diabetes duration, therefore measurement of both ABI and PWV is crucial for the cardiovascular risk assessment protocol for patients with T2DM and timely PAD diagnosis.

Unspoken Truths: Mental Health Among Academic Surgeons.

To characterize the current state of mental health within the surgical workforce in the United States. Mental illness and suicide is a growing concern in the medical community; however, the current state is largely unknown. Cross-sectional survey of the academic surgery community assessing mental health, medical error, and suicidal ideation. The odds of suicidal ideation adjusting for sex, prior mental health diagnosis, and validated scales screening for depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol use disorder were assessed. Of 622 participating medical students, trainees, and surgeons (estimated response rate=11.4%-14.0%), 26.1% (141/539) reported a previous mental health diagnosis. In all, 15.9% (83/523) of respondents screened positive for current depression, 18.4% (98/533) for anxiety, 11.0% (56/510) for alcohol use disorder, and 17.3% (36/208) for PTSD. Medical error was associated with depression (30.7% vs. 13.3%, P <0.001), anxiety (31.6% vs. 16.2%, P =0.001), PTSD (12.8% vs. 5.6%, P =0.018), and hazardous alcohol consumption (18.7% vs. 9.7%, P =0.022). Overall, 13.2% (73/551) of respondents reported suicidal ideation in the past year and 9.6% (51/533) in the past 2 weeks. On adjusted analysis, a previous history of a mental health disorder (aOR: 1.97, 95% CI: 1.04-3.65, P =0.033) and screening positive for depression (aOR: 4.30, 95% CI: 2.21-8.29, P <0.001) or PTSD (aOR: 3.93, 95% CI: 1.61-9.44, P =0.002) were associated with increased odds of suicidal ideation over the past 12 months. Nearly 1 in 7 respondents reported suicidal ideation in the past year. Mental illness and suicidal ideation are significant problems among the surgical workforce in the United States.

Enhanced robust diagnosis of multiple‐type demagnetisation fault for permanent magnet synchronous motor based on D‐axis magnetic network model using magnetic field reconstruction

AbstractDemagnetisation fault (DF) is a common rotor fault in the permanent magnet synchronous motor (PMSM). DF can cause obvious changes in the magnetic field of PMSMs. As a result, previous DF diagnosis methods mainly depends on magnetic field analysis. However, conventional analysis methods based on the magnetic potential‐permeability method, sub‐domain method and magnetic equivalent circuit method are not suitable for DF condition. In addition, DF diagnosis is further complicated by various operating conditions. To address these issues, a robust DF diagnosis method is proposed for PMSM based on d‐axis magnetic network model using magnetic field reconstruction. The proposed fault diagnosis method employs magnetic field reconstruction to obtain the radial air‐gap flux density under the open‐circuit condition. Subsequently, a d‐axis magnetic network is established to solve the demagnetisation coefficient matrix in the DF state. Finally, the effectiveness of the proposed method is validated through simulations and experiments. Both results demonstrate that the proposed method can accurately recognise uniform DF and partial DF with multiple demagnetised permanent magnets, exhibiting great robustness against different operating conditions.