Outcomes of patients undergoing third hematopoietic cell transplantation for hematologic malignancies.

With advancements in novel therapeutics, it is unclear whether third hematopoietic cell transplantation (HCT3) has a place in the treatment of recurrent hematopoietic malignancies. We evaluated patients with hematologic malignancies who underwent HCT3 between 2000-2020. Nine patients, with a median age of 18 (9-68) years at HCT3 with acute myelogenous leukemia (n = 5), acute lymphoblastic leukemia (n = 2), myelodysplastic syndrome (n = 1), or undifferentiated acute leukemia (n = 1), were identified. The median time between first HCT and HCT3 was 3.9 (0.7-13.6) years. Indication for HCT3 was relapse (n = 8) or graft failure (n = 1) after second HCT. At HCT3, seven of nine patients were in complete remission by flow cytometry. All experienced robust donor engraftment by one month after HCT3 (≥ 90% CD3) while one died at day + 24 of multi-organ failure and was not evaluable for chimerism. In total, eight patients died from relapse (n = 4), non-relapse, (n = 3) or unknown (n = 1) causes at a median of 0.6 (range, 0.1 - 9.9) years after HCT3. After HCT3, estimated overall survival at 6 months, 1 year, and 5 years was 88%, 63%, and 22%, respectively. In this highly selected group, HCT3 provided a treatment option although long-term survival was still dismal.

The impact of temperature on Ophthalmic Viscoelastic Devices and clinical implications - a pilot study: Temperature effect on Ophthalmic Viscoelastic Devices.

PURPOSE: To evaluate how temperature impacts the rheology of common Ophthalmic Viscoelastic Devices (OVDs) and clinical implications. SETTING: Tennent Institute of Ophthalmology, Glasgow, with Department of Mechanical and Aerospace Engineering, and Advanced Materials Research Laboratory, University of Strathclyde, Glasgow, UK. DESIGN: Laboratory pilot study. METHODS: The viscous and elastic responses of three OVDs (Eyefill-SC/Eyefill-C/Eyefill-HD; Bausch & Lomb) were measured using rotational and extensional rheometers at clinically relevant temperatures (5°C, 25°C, 37°C). Thermal properties were evaluated using differential scanning calorimetry and laser-flash analysis. RESULTS: The OVDs tested exhibited viscoelastic properties and shear-thinning behaviour. Apparent viscosities and relaxation time were higher at lower temperatures. The Eyefill-C and Eyefill-SC exhibited predominantly viscous character at low frequencies with a transition to predominantly elastic behaviour at high frequencies. An increase in temperature led to a decrease in relaxation time under shear and extension. At low frequencies, Eyefill-C and Eyefill-SC moduli increase with decreasing temperatures. Eyefill-HD at 25°C and 37°C displays two cross-over points, with the storage modulus dominating at low and high frequencies indicating a predominantly elastic behaviour. Thermal property analysis revealed Eyefill-C had the lowest thermal conductivity. CONCLUSIONS: This pilot study confirms our clinical experience that OVD properties are affected by low temperatures, with increased viscosities at low shear rates and higher relaxation times.Cold OVD can cause greater resistance to initiation of IOL injection system forces (compared to warmer OVD). Excessively forced injection using cold OVD could contribute to inadvertent cannula detachment if incorrectly assembled, or uncontrolled IOL release leading to avoidable injury.

Sex differences in neural projections of fear memory processing in mice and humans.

It remains unexplored in the field of fear memory whether functional neuronal connectivity between two brain areas is necessary for one sex but not the other. Here, we show that chemogenetic silencing of centromedial (CeM)-Tac2 fibers in the lateral posterior BNST (BNSTpl) decreased fear memory consolidation in male mice but not females. Optogenetic excitation of CeM-Tac2 fibers in the BNSTpl exhibited enhanced inhibitory postsynaptic currents in males compared to females. In vivo calcium imaging analysis revealed a sex-dimorphic fear memory engram in the BNSTpl. Furthermore, in humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) (TAC3R) decreased CeM-BNST connectivity in a fear task, impaired fear memory consolidation, and increased the expression of the TAC3R mRNA in AA-carrier men but not in women. These sex differences in critical neuronal circuits underlying fear memory formation may be relevant to human neuropsychiatric disorders with fear memory alterations such as posttraumatic stress disorder.

Superior Canal Dehiscence and the Risk of Additional Dehiscences: A Retrospective CT Cohort Study.

OBJECTIVE: Determine if superior canal dehiscence (SCD) found on flat-panel CT increases the risk for other defects in the otic capsule. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: One hundred ears (50 with SCD and 50 matched controls without SCD). INTERVENTIONS: Flat-panel CT imaging. MAIN OUTCOME MEASURES: (1) Prevalence of other dehiscences in SCD ears, (2) dehiscences in controls, and (3) otic capsule thickness in other reported dehiscence locations (cochlea-carotid, lateral semicircular canal [SCC] and mastoid, facial nerve-lateral SCC, vestibular aqueduct, posterior SCC-jugular bulb, posterior SCC-posterior fossa). Between-group comparisons were considered significant at p < 0.007 after applying the Bonferroni correction for multiple comparisons. RESULTS: Not including the SCD, there was a mean of 0.04 additional dehiscences in the SCD group (n = 2/50, 4%) and 0.04 non-SCD dehiscences in the controls (n = 2/50, 4%, p > 0.007). In the SCD group, there was one dehiscence between the cochlea and carotid artery and one between the posterior SCC and posterior fossa. The control group had one enlarged vestibular aqueduct and one dehiscence between the facial nerve and lateral SCC. As a group, SCD ears had wider vestibular aqueducts (0.68 ± 0.20 vs 0.51 ± 0.30 mm, p < 0.007) and thinner bone between the posterior SCC and posterior fossa (3.12 ± 1.43 vs 4.34 ± 1.67 mm, p < 0.007). The bone between the facial nerve and lateral SCC was thicker in SCD ears (0.77 ± 0.23 vs 0.55 ± 0.27 mm, p < 0.007) and no different for cochlea-carotid, and lateral SCC and mastoid (p > 0.007). CONCLUSIONS: SCD does not increase the likelihood of a second dehiscence in the same otic capsule. SCD patients may have congenitally thinner otic capsule bones compared to controls, particularly near the posterior SCC, where the vestibular aqueduct may be enlarged.

Regulators of rDNA array morphology in fission yeast.

Nucleolar morphology is a well-established indicator of ribosome biogenesis activity that has served as the foundation of many screens investigating ribosome production. Missing from this field of study is a broad-scale investigation of the regulation of ribosomal DNA morphology, despite the essential role of rRNA gene transcription in modulating ribosome output. We hypothesized that the morphology of rDNA arrays reflects ribosome biogenesis activity. We established GapR-GFP, a prokaryotic DNA-binding protein that recognizes transcriptionally-induced overtwisted DNA, as a live visual fluorescent marker for quantitative analysis of rDNA organization in Schizosaccharomyces pombe. We found that the morphology-which we refer to as spatial organization-of the rDNA arrays is dynamic throughout the cell cycle, under glucose starvation, RNA pol I inhibition, and TOR activation. Screening the haploid S. pombe Bioneer deletion collection for spatial organization phenotypes revealed large ribosomal protein (RPL) gene deletions that alter rDNA organization. Further work revealed RPL gene deletion mutants with altered rDNA organization also demonstrate resistance to the TOR inhibitor Torin1. A genetic analysis of signaling pathways essential for this resistance phenotype implicated many factors including a conserved MAPK, Pmk1, previously linked to extracellular stress responses. We propose RPL gene deletion triggers altered rDNA morphology due to compensatory changes in ribosome biogenesis via multiple signaling pathways, and we further suggest compensatory responses may contribute to human diseases such as ribosomopathies. Altogether, GapR-GFP is a powerful tool for live visual reporting on rDNA morphology under myriad conditions.

Variations in emergency hemorrhage panel turnaround times in 2 major medical centers using the same laboratory methods.

OBJECTIVES: Demand for rapid coagulation testing for massive transfusion events led to development of an emergency hemorrhage panel (EHP; hemoglobin, platelet count, prothrombin time/international normalized ratio, and fibrinogen), with laboratory turnaround time (TAT) of less than 20 minutes. Ten years on, we asked if current laboratory practices were meeting that TAT goal and differences were evident in TAT between the 2 major institutions in our system. METHODS: We identified EHPs ordered at our 2 largest hospitals, February 2, 2021, to July 17, 2022, comparing order to specimen draw time, specimen draw to specimen received time, laboratory analytic time, and total TAT results from emergency department and operating room. Site 1 houses a level I trauma center; site 2 includes tertiary care, transplant, and obstetrics services. RESULTS: In total, 1137 EHPs were recorded in our study period. Laboratory TAT was significantly faster at site 1 (~14 vs ~27 minutes, P < .01). Average laboratory TAT was under 20 minutes at site 1 but only for 50% of specimens at site 2. Outlier specimens were collection delays at site 1 and specimen processing delays at site 2. CONCLUSIONS: The EHP can be performed as rapidly as described. However, compromises in laboratory location, available personnel, and processing differences can degrade performance.

Necropsy findings in heart transplant recipients with or without primary graft dysfunction.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of death in the first year after heart transplant (HT), but pathophysiology and histology are not completely understood. This study describes and compares morphological findings of hearts of patients with and without PGD. METHODS: We included adult patients submitted to HT in a single center who died within the first 14 days after HT and were submitted to necropsy. Clinical and histological data were recorded retrospectively. All heart slides were reviewed by a blinded pathologist. We categorized patients in two groups (PGD and non-PGD) and compared findings between them. RESULTS: Among 322 HTs, 26 patients were included. Median age was 51.5 years, 57.7% were male, 46.1% had non-ischemic cardiomyopathy, 30.8% Chagas cardiomyopathy and 23% ischemic cardiomyopathy. Eleven patients presented PGD, while 15 patients did not. PGD was severe in 72.7% of cases and moderate in 27.3%. PGD group had longer ischemic time (p=0.08), higher incidence of mechanical circulatory support (p=0.004), lower post-transplant biventricular ejection fraction (p=0.005). However, necropsy findings were similar between groups. Necrosis was detected in 80.7% of all cases (p=0.907 comparing groups), taking ≥ 10% of myocardial area in 46.1% of them, and 4 types of necrosis were found either in patients with and without PGD. CONCLUSION: Cardiac pathological findings were similar in HT patients with or without PGD who died within 14 days after the transplant and necrosis was frequent in both groups, raising the hypothesis necrosis is not the cause of cardiac dysfunction in PGD.

Establishing normal Lindegaard Ratio in healthy children 10-16 years of age.

PURPOSE: Transcranial doppler based diagnostic criteria for cerebral vasospasm are not well established in the pediatric population because there is no published normative data to support the diagnosis. Studies have relied on expert consensus, but the definitions have not been validated in children diagnosed with angiographic evidence of vasospasm. Obtaining normative data is a prerequisite to defining pediatric cerebral vasospasm and the Lindegaard Ratio (LR). In this study, we obtained normative data and calculation of the normal LR from healthy children aged 10-16 years. METHODS: TCD and carotid ultrasonography was used to measure steady state velocities of both the middle cerebral artery (VMCA) and the extracranial internal cerebral artery (VEICA) in healthy children aged 10-16 years. Demographic information, hemodynamic characteristics and the calculated LR (VMCA/VEICA) was determined for each subject using descriptive statistics. RESULTS: Of the 26 healthy children, 13 were male and 13 were female. VMCA ranged between 53 and 93 cm/sec. LR ranged between 1 and 2.2 for the cohort. VMCA for both males and females were within 2 standard deviations (SD) of the normal mean flow velocity. As the VMCA velocities approached 2 SD above the mean, LR did not exceed 2.2. CONCLUSION: Our results help define a threshold for LR which can be used to establish radiographic criteria for cerebral vasospasm in children. Our data suggests that using VMCA criteria alone would overestimate cerebral vasospasm and raises question of whether an LR threshold other than 3 is more appropriate for the cut off between hyperemia versus vasospasm in children.

The relationship between healthcare satisfaction after miscarriage and perinatal grief symptoms: A cross-sectional study on Portugal residents.

OBJECTIVE: 15-20% of identified pregnancies result in miscarriage, which may lead to persistent symptoms of psychological morbidities in some women. Healthcare satisfaction is among the factors believed to influence such negative psychological responses. Here, we present the results of a study conducted in Portugal that analyzes the relationship between healthcare satisfaction, information and support provision and perinatal grief symptoms. METHODS: In a cross-sectional study, symptoms of perinatal grief, degree of satisfaction with healthcare received, and information and support provision data were collected through an online survey aimed at women in Portugal who suffered a miscarriage. 873 were considered eligible. Correlations were performed between perinatal grief scores and healthcare satisfaction rates. Finally, the proportions of information and support received were compared after distributing the sample in groups according to their perinatal grief levels. RESULTS: Healthcare satisfaction correlated significantly with perinatal grief scores, the latter increasing as satisfaction levels decreased. 61.1% of our sample received information about the physical consequences of miscarriage and showed a significantly lower rate of above-threshold perinatal grief symptoms in this group. 18.2% received information about its mental health consequences, with no significant differences in above-threshold symptom rates. 11.7% were offered or recommended mental health support, but no significant differences in above-threshold symptom rates were found. CONCLUSION: Healthcare satisfaction and information on after-miscarriage physical changes correlated significantly with reduced perinatal grief rates after miscarriage. However, any effects of mental health information and psychological support provision need further studies. Training for healthcare providers dealing with pregnancy loss, implementing national guidelines that include follow-up on the parents' physical and psychological health, and including a specialized area in medical structures are advised.

Social gradient and rural-urban disparities in cancer mortality in Costa Rica.

INTRODUCTION: Data on social inequalities in cancer mortality are sparse, especially in low- and middle-income countries. We aimed to analyze the socioeconomic inequalities in cancer mortality in Costa Rica between 2010 and 2018. METHODS: We linked 9-years of data from the National Electoral Rolls, National Birth Index and National Death Index to classify deaths due to cancer and socioeconomic characteristics of the district of residence, as measured by levels of urbanicity and wealth. We analyzed the fifteen most frequent cancer sites in Costa Rica among the 2.7 million inhabitants aged 20 years and older. We used a parametric survival model based on a Gompertz distribution. RESULTS: Compared to urban areas, mixed and rural area residents had lower mortality from pancreas, lung, breast, prostate, kidney, and bladder cancers, and higher mortality from stomach cancer. Mortality from stomach, lung and cervical cancer was higher, and mortality from colorectal cancer, non-Hodgkin lymphoma and leukemia was lower in the most disadvantaged districts, compared to the wealthiest ones. CONCLUSION: We observed marked disparities in cancer mortality in Costa Rica in particular from infection- and lifestyle- related cancers. There are important opportunities to reduce disparities in cancer mortality by targeting cancer prevention, early detection and opportune treatment, mainly in urban and disadvantaged districts.

Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

Exploring Integrin α5ß1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights from Comprehensive Multicenter Preclinical Studies.

Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PA) and progressive increase in pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Although several drugs are approved for the treatment of PAH, mortality remains high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets. However, their role in PAH remains largely unexplored. We found that the arginine-glycine-aspartate (RGD)-binding integrin α5ß1 is upregulated in PA endothelial cells (PAEC) and PA smooth muscle cells (PASMC) from PAH patients and remodeled PAs from animal models. Blockade of the integrin α5ß1 or depletion of the α5 subunit resulted in mitotic defects and inhibition of the pro-proliferative and apoptosis-resistant phenotype of PAH cells. Using a novel small molecule integrin inhibitor and neutralizing antibodies, we demonstrated that α5ß1 integrin blockade attenuates pulmonary vascular remodeling and improves hemodynamics and RV function in multiple preclinical models. Our results provide converging evidence to consider α5ß1 integrin inhibition as a promising therapy for pulmonary hypertension. One sentence summary: The α5ß1 integrin plays a crucial role in pulmonary vascular remodeling.

Racial and Ethnic Differences in Time to Completion of Academic Enrichment Program Applications.

INTRODUCTION: Diversity in healthcare and research is integral to serving our increasingly diverse population. Access to academic enrichment programs, an important pathway to science, technology, engineering, and mathematics (STEM) careers promotes educational attainment through academic preparation and increased interest, useful strategies for improving diverse representation in higher learning. Given this important pathway to STEM fields, attention to equity in enrichment programs admissions is as important as the increasing focus on mitigating racial/ethnic disparities in undergraduate and graduate admissions.  Methods: In a retrospective cohort study at the University of Washington, we used descriptive and Chi-Square statistics to compare a hybrid competitive summer application program with stipend with an asynchronous first-come, first-served enrollment program in injury and violence prevention research. The three main outcomes were: 1) time to application, measured by number of days to apply/enroll after application or enrollment period start date, 2) percentage of application/enrollment period, measured by when application or enrollment occurred in relation to the total application or enrollment period, and 3) differences in Black, Hispanic, and Native American applicants and enrollees.  Results: In a study examining two injury and violence prevention programs, which reached educational institutions including Historically Black Colleges and Universities (HBCU) and Tribal Colleges: 1) Applicants were 9.6% and 6.4% Black (application vs enrollment programs; p<0.0001), 0.4% and 0% Native American to the application and enrollment programs, and 9.1% and 10.3% Hispanic (application vs enrollment programs; p=0.6), 2) Across all racial and ethnic groups, students applied later (last 15% percent of application period) in the competitive application program than to the first-come first-served enrollment program in which students enrolled throughout the enrollment period, and 3) Across both program types, there were racial and ethnic differences in time to application and enrollment start and completion. CONCLUSION: Findings show that free enrollment programs alone do not incentivize educational attainment for all groups and that application rolling admissions processes may not equally promote racial and ethnic diversity for all groups.

Perme ICU Physical Therapy Competency: Development of an ICU Knowledge and Skills Assessment Tool.

BACKGROUND: Physical therapy for patients in the ICU is advanced practice demanding specialized knowledge and skills. However, ICU physical therapy competency standards lack uniformity or defined processes. OBJECTIVES: To describe the development process of the Perme ICU Physical Therapy Competency and to assess its face and content validity. METHODS: Quantitative research study for the content validation of the Perme ICU Physical Therapy Competency using a panel of experts. The face validity assessment consisted of two informal surveys and discussions with clinicians representing various disciplines in ICU. MAIN OUTCOME MEASURES: A content validation survey included analysis of sufficiency, clarity, coherence, and relevance for items in the Perme ICU Physical Therapy Competency. For the quantitative analysis of content validity, the item-level content validity index (I-CVI) was used. Scale-level content validity index based on the universal agreement method (S-CVI/UA) was calculated as the proportion of items on the scale that achieve a relevance scale of 3 or 4 by all experts. Scale-level content validity index was calculated based on the average method (S-CVI/Ave). RESULTS: The sufficiency, clarity, coherence, and relevance of the Perme ICU Physical Therapy Competency items presented S-CVI/Ave greater than 80 % (97 %, 97 %, 99 %, 95 %, respectively). CONCLUSION: This study establishes that the Perme ICU Physical Therapy Competency has a satisfactory level of face and content validity. IMPLICATIONS FOR CLINICAL PRACTICE: The Perme ICU Physical Therapy Competency, with its solid framework, is a valuable assessment tool applicable for integration in any ICU competency program. It can be utilized as a self-assessment tool by individual therapists or in collaboration with mentors and evaluators to evaluate knowledge and skills effectively. This innovative tool not only enhances clinical practice but also presents an opportunity for advancing the physical therapy profession within the ICU setting.

Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects.

Background: Anti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of patients with high-risk neuroblastoma (HR-NB). Serious adverse events (AEs), including pain, within hours of antibody infusion, have limited the development of these therapies. In this study, we provide evidence of Autonomic Nervous System (ANS) activation as the mechanism to explain the main side effects of anti-GD2 mAbs. Methods: Through confocal microscopy and computational super-resolution microscopy experiments we explored GD2 expression in postnatal nerves of infants. In patients we assessed the ANS using the Sympathetic Skin Response (SSR) test. To exploit tachyphylaxis, a novel infusion protocol (the Step-Up) was mathematically modelled and tested. Results: Through confocal microscopy, GD2 expression is clearly visible in the perineurium surrounding the nuclei of nerve cells. By computational super-resolution microscopy experiments we showed the selective expression of GD2 on the cell membranes of human Schwann cells in peripheral nerves (PNs) significantly lower than on NB. In patients, changes in the SSR were observed 4 minutes into the anti-GD2 mAb naxitamab infusion. SSR latency quickly shortened followed by gradual decrease in the amplitude before disappearance. SSR response did not recover for 24 hours consistent with tachyphylaxis and absence of side effects in the clinic. The Step-Up protocol dissociated on-target off-tumor side effects while maintaining serum drug exposure. Conclusion: We provide first evidence of the ANS as the principal non-tumor target of anti-GD2 mAbs in humans. We describe the development and modeling of the Step-Up protocol exploiting the tachyphylaxis phenomenon we demonstrate in patients using the SSR test.

Real-World Treatment Patterns Among Patients with Type 2 Diabetes Mellitus Initiating Treatment with Oral Semaglutide.

INTRODUCTION: The treatment landscape for type 2 diabetes mellitus (T2DM) is complex and constantly evolving, and real-world evidence of prescribing patterns is limited. The objectives of this study were to characterize lines of therapy (LOTs), calculate the length of time spent on each LOT, and identify the reasons for the LOT end among patients who initiated oral semaglutide for T2DM. METHODS: This retrospective, claims-based study included commercial and Medicare Advantage adults with T2DM. Data from November 1, 2019, and June 30, 2020, were obtained from Optum Research Database. Patients with ≥ 1 claim for oral semaglutide and continuous health plan enrollment for ≥ 12 months prior to (baseline period) and ≥ 6 months following (follow-up period) the date of the first oral semaglutide claim were included. LOT 1 began on the date of the first oral semaglutide claim. The start date of any subsequent LOTs was the date of the first claim for an additional non-insulin anti-diabetic drug class or a reduction in drug class with use of commitment medications. The LOT ended at the first instance of medication class discontinuation, change in regimen or end of follow-up. RESULTS: Of the 1937 patients who initiated oral semaglutide, 950 (49.0%) remained on their initial regimen over the 6-month follow-up period, 844 (43.6%) had at least one subsequent LOT, and 89 (4.6%) had at least two subsequent LOTs. Among patients with more than one LOT, approximately 20%-25% used oral semaglutide as monotherapy or combination therapy during LOTs 2 and 3. Metformin was frequently used during treatment across all LOTs. CONCLUSION: This study provides insight for physicians and payers into the real-world prescribing practices within the first 6 months following oral semaglutide initiation and fills the gap in understanding the frequency of regimen changes in the constantly evolving and complex environment of T2DM care.

Type 2 diabetes mellitus is a disease which, over time, can cause higher than normal levels of sugar in the blood (hyperglycemia) which can be harmful if not treated. Treatment for type 2 diabetes mellitus can be complex, and how doctors prescribe medications is always changing. For some people with type 2 diabetes mellitus who are overweight or obese, it is recommended for patients to use certain medications that can help with weight management such as semaglutide and metformin. This study aims to fill gaps in current treatment knowledge about type 2 diabetes mellitus patients and their treatment of oral semaglutide. Researchers in this study explored how patients treated with oral semaglutide differentiated among line of therapies, how long patients stuck to them and why they stopped. The study found that those patients who started with oral semaglutide, almost half of those patients stuck to their initial treatment plan for the entire 6 months. When it came to the top ten treatment plans, about 20% of patients used oral semaglutide alone and about 25% of patients used oral semaglutide plus an additional treatment option. Metformin was frequently used during treatment across all line of therapies. There is little information on the real-life setting of treatment after the start of therapy for type 2 diabetes mellitus. The results from this study show what happens when patients start using oral semaglutide and helps healthcare providers understand how often treatment plans can change in type 2 diabetes mellitus care.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

Protective role for kidney TREM2high macrophages in obesity- and diabetes-induced kidney injury.

Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression-high-fat diet (HFD)-fed mice aged to 90-100 weeks and BTBR ob/ob mice (a genetic model)-and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD.

Acupuncture knowledge, attitudes, beliefs and health service needs after traumatic brain injury: a cross-sectional survey.

BACKGROUND: Acupuncture is a promising treatment for common symptoms after traumatic brain injury (TBI). Our objectives were to explore knowledge, attitudes and beliefs about acupuncture, identify health service needs and assess the perceived feasibility of weekly acupuncture visits among individuals with TBI. METHODS: We surveyed adults 18 years of age and older with TBI who received care at the University of Washington. Respondents were asked to complete 143 questions regarding acupuncture knowledge, attitudes and beliefs, injury-related symptoms and comorbidities, and to describe their interest in weekly acupuncture. RESULTS: Respondents (n = 136) reported a high degree of knowledge about acupuncture as a component of Traditional Chinese Medicine, needle use and safety, but were less knowledgeable regarding that the fact that most conditions require multiple acupuncture treatments to achieve optimal therapeutic benefit. Respondents were comfortable talking with healthcare providers about acupuncture (63.4%), open to acupuncture concurrent with conventional treatments (80.6%) and identified lack of insurance coverage as a barrier (50.8%). Beliefs varied, but respondents were generally receptive to using acupuncture as therapy. Unsurprisingly, respondents with a history of acupuncture (n = 60) had more acupuncture knowledge than those without such a history (n = 66) and were more likely to pursue acupuncture without insurance (60%), for serious health conditions (63.3%) or alongside conventional medical therapy (85.0%). Half of all respondents expressed interest in participating in weekly acupuncture for up to 12 months and would expect almost a 50% improvement in symptoms by participating. CONCLUSION: Adults with TBI were receptive and interested in participating in weekly acupuncture to address health concerns. These results provide support for exploring the integration of acupuncture into the care of individuals with TBI.

Improving Post-Injury Follow-up Survey Response: Incorporating Automated Modalities.

Background: Incorporating post-discharge data into trauma registries would allow for better research on patient outcomes, including disparities in outcomes. This pilot study tested a follow-up data collection process to be incorporated into existing trauma care systems, prioritizing low-cost automated response modalities. Methods: This investigation was part of a larger study that consisted of two protocols with two distinct cohorts of participants who experienced traumatic injury. Participants in both protocols were asked to provide phone, email, text, and mail contact information to complete follow-up surveys assessing patient-reported outcomes six months after injury. To increase follow-up response rates between protocol 1 and protocol 2, the study team modified the contact procedures for the protocol 2 cohort. Frequency distributions were utilized to report the frequency of follow-up response modalities and overall response rates in both protocols. Results: A total of 178 individuals responded to the 6-month follow-up survey: 88 in protocol 1 and 90 in protocol 2. After implementing new follow-up contact procedures in protocol 2 that relied more heavily on the use of automated modalities (e.g., email and text messages), the response rate increased by 17.9 percentage points. The primary response modality shifted from phone (72.7%) in protocol 1 to the combination of email (47.8%) and text (14.4%) in protocol 2. Conclusions: Results from this investigation suggest that follow-up data can feasibly be collected from trauma patients. Use of automated follow-up methods holds promise to expand longitudinal data in the national trauma registry and broaden the understanding of disparities in patient experiences.