bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognizing, defining, and managing CAR-T hematologic toxicities
Authors: Rejeski Kai , Subklewe Marion , Locke Frederick L.
Published: December 2023

Autologous CAR-T cell therapy (CAR-T) has improved outcomes for patients with B-cell malignancies. It is associated with the well-described canonical toxicities cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which may be abrogated by corticosteroids and the anti-IL6 receptor antagonist tocilizumab. Practitioners and researchers should be aware of additional toxicities. Here we review current understanding and management of hematologic toxicities after CAR-T, including cytopenias, coagulopathies, bleeding and clotting events, hemophagocytic-lymphohistiocytosis, and tumor lysis syndrome. We pay particular attention to cytopenias, recently termed immune effector cell-associated hematological toxicity (ICAHT). While the “H” is silent, hematotoxicity is not: ICAHT has the highest cumulative incidence of all immune adverse events following CAR-T. Early cytopenia (day 0-30) is closely linked to lymphodepleting chemotherapy and CRS-related inflammatory stressors. Late ICAHT (after day 30) can present either with or without antecedent count recovery (e.g., “intermittent” vs “aplastic” phenotype), and requires careful evaluation and management strategies. Growth factor support is the mainstay of treatment, with recent evidence demonstrating safety and feasibility of early granulocyte colony-stimulating factor (G-CSF) (e.g., within week 1). In G-CSF refractory cases, autologous stem cell boosts represent a promising treatment avenue, if available. The CAR-HEMATOTOX scoring system, validated for use across lymphoid malignancies (B-NHL, multiple myeloma), enables pretherapeutic risk assessment and presents the potential for risk-adapted management. Recent expert panels have led to diagnostic scoring criteria, severity grading systems, and management strategies for both ICAHT and the recently termed immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), now clarified and defined as a distinct entity from CRS.
Clonal hematopoiesis in frequent whole blood donors
Authors: Karpova Darja
Published: December 2023

Healthy volunteer donors are committed to contributing key medical resources. Repeated, regular donation of whole blood represents a specific trigger of hematopoietic stress. Hematopoietic stem cells (HSCs) are known to respond to environmental triggers by altering their differentiation and/or proliferative behavior. This can manifest in long-term changes in the clonal dynamics of HSCs, such as the age-associated expansion of HSCs carrying somatic mutations in genes associated with hematologic cancers—that is, clonal hematopoiesis (CH). A recent study revealed a higher prevalence of CH in frequent donors driven by low-risk mutations in genes encoding for epigenetic modifiers, with DNMT3A and TET2 being the most common. No difference in the prevalence of known preleukemic driver mutations was detected between the cohorts, underscoring the safety of repetitive blood donations. Functional analyses suggest a link between the presence of selected DNMT3A mutations found in the frequent donor group and the responsiveness of the cells to the molecular mediator of bleeding stress, erythropoietin (EPO), but not inflammation. These findings define EPO as one of the environmental factors that provide a fitness advantage to specific mutant HSCs. Analyzing CH prevalence and characteristics in other donor cohorts will be important to comprehensively assess the health risks associated with the different types of donation.
The dos, don'ts, and nuances of thrombophilia testing
Authors: Chiasakul Thita , Bauer Kenneth A.
Published: December 2023

Considerable progress has been made in elucidating genetic and biologic risk factors for venous thromboembolism (VTE). Despite being able to identify heritable defects in a substantial proportion of patients with VTE, testing has not, in general, proven useful in management. Despite efforts to reduce inappropriate testing, it often falls to the hematologist to consult on patients having undergone thrombophilia testing. Through a series of cases, we discuss how D-dimer testing can be helpful in VTE recurrence risk stratification in younger women as well as how to approach patients with persistently elevated D-dimer levels in the absence of thrombosis. While elevated factor VIII coagulant activity levels are a significant risk factor for a first episode of VTE, its biologic basis is not fully understood, and studies have not shown it to be a useful predictor of recurrence. Abnormal results of genetic tests for methylene tetrahydrofolate reductase or plasminogen activator 1 promoter polymorphisms may be encountered, which carry little if any thrombotic risk and should never be ordered. We also discuss protein S deficiency, the most difficult of the hereditary thrombophilias to diagnose due to a wider “normal” range in the general population as compared with protein C, the presence of both free and bound forms in plasma, and the characteristics of the various assays in use. We also present a rare type of protein C deficiency that can be missed by functional assays using an amidolytic rather than a clotting end point.
How to diagnose and manage antiphospholipid syndrome
Authors: Hubben Anne , McCrae Keith R.
Published: December 2023

Antiphospholipid antibodies (aPL) are autoimmune antibodies directed toward phospholipids or phospholipid-protein complexes, particularly those containing β2-glycoprotein I (β2GPI). Persistently positive aPL accompanied by arterial or venous thrombosis, or recurrent pregnancy loss, constitutes the antiphospholipid syndrome (APS). Several types of aPL with different specificities have been defined and may be detected in the clinical lab, including lupus anticoagulants (detected using clotting assays) and anticardiolipin, anti-β2GPI and anti-prothrombin/phosphatidylserine antibodies (detected by ELISA); each of the last 3 aPL may be either IgG, IgM, or IgA, though IgA antibodies are not included in criteria for APS. Due to the relative rarity of APS and the heterogeneity of aPL, thrombosis risk stratification is challenging, and randomized clinical trials for thrombosis treatment and prevention have been limited. This lack of high-quality data has made the clinical management of APS difficult, and existing guidelines are few and could not possibly cover many of the scenarios encountered in managing patients with APS. In this review, we present 3 patients with aPL and/or APS who highlight treatment dilemmas, and we discuss background information that may help guide clinical judgment in developing individualized treatment plans for patients with these enigmatic antibodies.
Sex, lies, and iron deficiency: a call to change ferritin reference ranges
Authors: Martens Kylee , DeLoughery Thomas G.
Published: December 2023

Iron deficiency is a very common and treatable disorder. Of all the tests available to diagnose iron deficiency, the serum ferritin is the most able to discriminate iron deficiency from other disorders. However, the reference range for ferritin in many laboratories will lead to underdiagnosis of iron deficiency in women. Studies have shown that 30%-50% of healthy women will have no marrow iron stores, so basing ferritin cutoffs on the lowest 2.5% of sampled ferritins is not appropriate. In addition, several lines of evidence suggest the body physiologic ferritin “cutoff” is 50  ng/mL. Work is needed to establish more realistic ferritin ranges to avoid underdiagnosing a readily treatable disorder.
Intravenous iron therapy in pediatrics: who should get it and when is the right time?
Authors: Cohen Clay T. , Powers Jacquelyn M.
Published: December 2023

Iron-deficiency anemia occurs most commonly in young children due to a low-iron diet and adolescent girls due to menstrual blood loss. However, children with gastrointestinal conditions such as intestinal failure, inflammatory bowel disease, celiac disease, and/or other chronic conditions, including chronic kidney disease and heart failure, also commonly have iron deficiency. Many patients with classic iron-deficiency anemia will improve with oral iron therapy. However, in children who have an incomplete response to oral iron, intravenous iron therapy is increasingly being used. Benefits of intravenous iron therapy include a rapid repletion of iron stores in addition to resolution of anemia, less gastrointestinal side effects, and relief for patients and families struggling with long-term iron supplementation. Indications for first-line therapy with intravenous iron in children with chronic conditions have also increased. Four intravenous iron formulations have approved indications in pediatrics, and many are increasingly used off-label in children as well. Here we discuss the indications and appropriate timing of intravenous iron therapy in children with a wide range of underlying etiologies.
Alloimmunization and hyperhemolysis in sickle cell disease
Authors: Pirenne France , Pondarré Corinne
Published: December 2023

Alloimmunization against red blood cell antigens and delayed hemolytic transfusion reaction (DHTR) are major barriers to transfusion in sickle cell disease (SCD). In SCD, DHTR is a potentially life-threatening. Blood group polymorphism in SCD patients, who are of African ancestry and frequently exposed to antigens they do not carry; an inflammatory clinical state; and occasional transfusion in acute situations are risk factors for alloimmunization and DHTR. In patients at risk, the transfusion indication must be balanced against the risk of developing DHTR. However, when transfusion is absolutely necessary, protocols combining the prevention of exposure to immunogenic antigens with immunosuppressive treatments must be implemented, and patients should be carefully monitored during posttransfusion follow-up. This close monitoring makes it possible to diagnose hyperhemolysis as soon as possible; to avoid retransfusion, which can exacerbate hemolysis; and to administer specific treatments, such as anticomplement therapy, in severe cases. Finally, in patients with severe disease, hematopoietic stem cell transplantation may be indicated. However, transfusion is also required in this context, and its management is complex because these risks must be taken into account.
Consumptive coagulopathy in the ICU
Authors: Retter Andrew , Hunt Beverley J.
Published: December 2023

A consumptive coagulopathy describes a situation where there is a loss of hemostatic factors, which leads to an increased risk of bleeding. Some recent studies have used the term interchangeably with disseminated intravascular coagulation (DIC), but we have reverted to the older definition, which covers a broader range of issues where there is loss of hemostatic factors due to multiple causes, which includes systemic activation of coagulation as seen in DIC. Therefore, the term consumptive coagulopathy covers conditions from the hemostatic effects of major hemorrhage to the use of extracorporeal circuits to true DIC. We review the current understanding of the pathophysiology, diagnosis, and management of common consumptive coagulopathy in critical care patients, focusing on recent advances and controversies. Particular emphasis is given to DIC because it is a common and often life-threatening condition in critical care patients and is characterized by the simultaneous occurrence of widespread microvascular thrombosis and bleeding. Second, we focus on the effect of modern medical technology, such as extracorporeal membrane oxygenation, on hemostasis.
Thrombotic anti-PF4 immune disorders: HIT, VITT, and beyond
Authors: Greinacher Andreas , Warkentin Theodore E.
Published: December 2023

Antibodies against the chemokine platelet factor 4 (PF4) occur often, but only those that activate platelets induce severe prothrombotic disorders with associated thrombocytopenia. Heparin-induced thrombocytopenia (HIT) is the prototypic anti-PF4 disorder, mediated by strong activation of platelets through their FcγIIa (immunoglobulin G [IgG]) receptors (FcγRIIa). Concomitant pancellular activation (monocytes, neutrophils, endothelium) triggers thromboinflammation with a high risk for venous and arterial thrombosis. The classic concept of HIT is that anti-PF4/heparin IgG, recognizing antigen sites on (cationic) PF4 that form in the presence of (anionic) heparin, constitute the heparin-dependent antibodies that cause HIT. Accordingly, HIT is managed by anticoagulation with a nonheparin anticoagulant. In 2021, adenovirus vector COVID-19 vaccines triggered the rare adverse effect “vaccine-induced immune thrombotic thrombocytopenia” (VITT), also caused by anti-PF4 IgG. VITT is a predominantly heparin-independent platelet-activating disorder that requires both therapeutic-dose anticoagulation and inhibition of FcγRIIa-mediated platelet activation by high-dose intravenous immunoglobulin (IVIG). HIT and VITT antibodies bind to different epitopes on PF4; new immunoassays can differentiate between these distinct HIT-like and VITT-like antibodies. These studies indicate that (1) severe, atypical presentations of HIT (“autoimmune HIT”) are associated with both HIT-like (heparin-dependent) and VITT-like (heparin-independent) anti-PF4 antibodies; (2) in some patients with severe acute (and sometimes chronic, recurrent) thrombosis, VITT-like antibodies can be identified independent of proximate heparin exposure or vaccination. We propose to classify anti-PF4 antibodies as type 1 (nonpathogenic, non– platelet activating), type 2 (heparin dependent, platelet activating), and type 3 (heparin independent, platelet activating). A key concept is that type 3 antibodies (autoimmune HIT, VITT) require anticoagulation plus an adjunct treatment, namely high-dose IVIG, to deescalate the severe anti-PF4 IgG-mediated hypercoagulability state.
Mastocytosis demystified
Authors: Veitch Scott , Radia Deepti H.
Published: December 2023

Mastocytosis is a rare, clinically heterogenous clonal hematological neoplasm. Over 95% of patients harbor the driver KIT D816V mutation resulting in mast cell (MC) accumulation and proliferation in various organs, leading to variable symptom manifestations that result from MC mediator release in patients with systemic mastocytosis (SM) and end-organ damage in those with advanced SM. The accurate diagnostic and clinical classification of patients with SM is vital to underpin appropriate treatment options and personalize therapy. This review evaluates the current diagnostic criteria, clinical classification, risk stratification, and therapeutic options available for adult patients with nonadvanced and advanced SM.
Variable Curvature Modeling Method of Soft Continuum Robots with Constraints
Authors: Liu Yuwang , Shi Wenping , Chen Peng , Cheng Liang , Ding Qing , Deng Zhaoyan
Published: December 2023

The inherent compliance of continuum robots holds great promise in the fields of soft manipulation and safe human–robot interaction. This compliance reduces the risk of damage to the manipulated object and its surroundings. However, continuum robots possess theoretically infinite degrees of freedom, and this high flexibility usually leads to complex deformations when subjected to external forces and positional constraints. Describing these complex deformations is the main challenge in modeling continuum robots. In this study, we investigated a novel variable curvature modeling method for continuum robots, considering external forces and positional constraints. The robot configuration curve is described using the developed mechanical model, and then the robot is fitted to the curve. A ten-section continuum robot prototype with a length of 1 m was developed in order to validate the model. The feasibility and accuracy of the model were verified by the ability of the robot to reach target points and track complex trajectories with a load. This work was able to serve as a new perspective for the design analysis and motion control of continuum robots.
Regulator of G protein signaling protein 6 alleviates acute lung injury by inhibiting inflammation and promoting cell self-renewal in mice
Authors: Song Juan , Li Miao , Chen Cuicui , Zhou Jian , Wang Linlin , Yan Yu , She Jun , Tong Lin , Song Yuanlin
Published: December 2023

Background

Acute respiratory distress syndrome (ARDS) is a disease with high mortality and morbidity. Regulator of G protein signaling protein 6 (RGS6), identified as a tumor suppressor gene, has received increasing attention owing to its close relationship with oxidative stress and inflammation. However, the association between ARDS and RGS6 has not been reported.

Methods

Congruously regulated G protein-coupled receptor (GPCR)-related genes and differentially expressed genes (DEGs) in an acute lung injury (ALI) model were identified, and functional enrichment analysis was conducted. In an in vivo study, the effects of RGS6 knockout were studied in a mouse model of ALI induced by lipopolysaccharide (LPS). HE staining, ELISA, and immunohistochemistry were used to evaluate pathological changes and the degree of inflammation. In vitro, qRT‒PCR, immunofluorescence staining, and western blotting were used to determine the dynamic changes in RGS6 expression in cells. The RGS6 overexpression plasmid was constructed for transfection. qRT‒PCR was used to assess proinflammatory factors transcription. Western blotting and flow cytometry were used to evaluate apoptosis and reactive oxygen species (ROS) production. Organoid culture was used to assess the stemness and self-renewal capacity of alveolar epithelial type II cells (AEC2s).

Results

A total of 110 congruously regulated genes (61 congruously upregulated and 49 congruously downregulated genes) were identified among GPCR-related genes and DEGs in the ALI model. RGS6 was downregulated in vivo and in vitro in the ALI model. RGS6 was expressed in the cytoplasm and accumulated in the nucleus after LPS stimulation. Compared with the control group, we found higher mortality, more pronounced body weight changes, more serious pulmonary edema and pathological damage, and more neutrophil infiltration in the RGS6 knockout group upon LPS stimulation in vivo. Moreover, AEC2s loss was significantly increased upon RGS6 knockout. Organoid culture assays showed slower alveolar organoid formation, fewer alveolar organoids, and impaired development of new structures after passaging upon RGS6 knockout. In addition, RGS6 overexpression decreased ROS production as well as proinflammatory factor transcription in macrophages and decreased apoptosis in epithelial cells.

Conclusions

RGS6 plays a protective role in ALI not only in early inflammatory responses but also in endogenous lung stem cell regeneration.

Graphical Abstract
Preoptic and hypothalamic regulation of multi-tiered, chronologically arranged female rat sexual behavior
Authors: Sakuma Yasuo
Published: December 2023

As in many mammalian behaviors, sexual behavior exhibits structure. Each modular components of the structure, that are linked together over time, occur in probabilistic manner. Endocrine milieu, in particular sex hormones, define the probability to synchronize the behavior with the production of gametes. Developmental experience and environmental cues affect the hormonal milieu of the brain. This is especially true in female mammals, in which ova mature with certain intervals along with ovarian secretion of sex hormones. Estrogens secreted by mature ovarian follicles support both affiliative and executive components of female sexual behavior. In the absence of the ovarian steroids, females avoid males when possible, or antagonize and reject males when put together. Female sexual behavior is intimately linked with the estrous cycle in many species such that females are only receptive for a brief period at the estrus stage surrounding ovulation. Thus, in the rat, females strongly influence the outcome of mating encounter with a male. Affiliative or solicitatory behavior shown by females in estrus leads to the female adapting the lordosis posture, which is characterized by hindleg postural rigidity and lordotic dorsiflexion of the spine, in response to touch-pressure somatosensory stimuli on the skin of the flanks, rump-tail base, perineum region given by male partner. The posture facilitates intromission and consequently fertilization. Although dependence on estrogens is the most important feature of female rat sexual behavior, cervical probing combined with palpation of the hindquarter skin acts as a supranormal stimulus to elicit lordosis. Thus, lordosis behavior is a hub of multi-tiered, chronologically arranged set of behaviors and estrogen appear to alter excitability of neural network for lordosis.
Microsatellites reveal divergence in population genetic diversity, and structure of osyris lanceolata (santalaceae) in Uganda and Kenya
Authors: Mugula Ben Belden , Omondi S. F. , Curto Manuel , Kiboi Samuel Kuria , Kanya James Ireri , Egeru Anthony , Okullo Paul , Meimberg Harald
Published: December 2023

Background

Osyris lanceolata (Hochst. & Steud.) (Santalaceae) is a multipurpose plant highly valued culturally and economically in Africa. However, O. lanceolata populations have rapidly dwindled in East Africa due to overexploitation and this is believed to cause further consequences on the species’ genetic diversity and structure within the region. Information regarding a species’ genetic diversity and structure is necessary for conservation but this is currently lacking for O. lanceolata in Uganda and Kenya. Lack of adequate scientific data hinders conservation efforts hence threatening the species survival and livelihoods. This study investigated patterns in genetic diversity and structure of O. lanceolata in Uganda and Kenya. Ten polymorphic microsatellite loci were used to genotype 210 individuals: 96 from Ugandan and 114 from Kenyan populations.

Results

All populations were highly polymorphic (80–100% polymorphism). A genetic differentiation was found between Kenyan and Ugandan populations. The highest genetic differentiation was among individuals and the least among populations. The Kenyan populations showed higher genetic diversity than Ugandan populations. The Ugandan populations showed more marker deviations from Hardy-Weinberg equilibrium and inbreeding coefficient. Two populations showed evidence of going through a recent bottleneck. There was significant genetic differentiation and structuring at higher K values into larger clusters and observed admixture between populations. The populations were significantly isolated by altitude as opposed to distance and climatic variables. Main barriers were associated with altitude differences. The data supports the idea of long-distance gene-flow between high altitude populations in both countries.

Conclusion

The divergence in genetic structure suggests unrecognised taxonomic units within O. lanceolata which are characteristic to lower altitudes and higher altitudes including most Kenyan populations with divergent evolutionary patterns. Geographical barriers and environmental gradients could have influenced this genetic divergence, and such patterns may escalate the species microevolutionary processes into full allopatric speciation. Further investigations into the species’ genetic admixture and emerging taxonomic units are necessary to guide conservation strategies in the region.
Full-length transcriptome characterization and comparative analysis of Gleditsia sinensis
Authors: Xiao Feng , Zhao Yang , Wang Xiurong , Jian Xueyan
Published: December 2023

As an economically important tree, Gleditsia sinensis Lam. is widely planted. A lack of background genetic information on G. sinensis hinders molecular breeding. Based on PacBio single-molecule real-time (SMRT) sequencing and analysis of G. sinensis, a total of 95,183 non-redundant transcript sequences were obtained, of which 93,668 contained complete open reading frames (ORFs), 2,858 were long non-coding RNAs (LncRNAs) and 18,855 alternative splicing (AS) events were identified. Genes orthologous to different Gleditsia species pairs were identified, stress-related genes had been positively selected during the evolution. AGA, AGG, and CCA were identified as the universal optimal codon in the genus of Gleditsia. EIF5A was selected as a suitable fluorescent quantitative reference gene. 315 Cytochrome P450 monooxygenases (CYP450s) and 147 uridine diphosphate (UDP)-glycosyltransferases (UGTs) were recognized through the PacBio SMRT transcriptome. Randomized selection of GsIAA14 for cloning verified the reliability of the PacBio SMRT transcriptome assembly sequence. In conclusion, the research data lay the foundation for further analysis of the evolutionary mechanism and molecular breeding of Gleditsia.
Karyotyping of aneuploid and polyploid plants from low coverage whole-genome resequencing
Authors: Zhao Kanglu , Bai Yanbo , Zhang Qingyu , Zhao Zhen , Cao Yao , Yang Lu , Wang Ni , Xu Junxiong , Wang Bo , Wu Lei , Gong Xiufeng , Lin Tuanrong , Wang Yufeng , Wang Wei , Cai Xingkui , Yin Yuhe , Xiong Zhiyong
Published: December 2023

Background

Karyotype, as a basic characteristic of species, provides valuable information for fundamental theoretical research and germplasm resource innovation. However, traditional karyotyping techniques, including fluorescence in situ hybridization (FISH), are challenging and low in efficiency, especially when karyotyping aneuploid and polyploid plants. The use of low coverage whole-genome resequencing (lcWGR) data for karyotyping was explored, but existing methods are complicated and require control samples.

Results

In this study, a new protocol for molecular karyotype analysis was provided, which proved to be a simpler, faster, and more accurate method, requiring no control. Notably, our method not only provided the copy number of each chromosome of an individual but also an accurate evaluation of the genomic contribution from its parents. Moreover, we verified the method through FISH and published resequencing data.

Conclusions

This method is of great significance for species evolution analysis, chromosome engineering, crop improvement, and breeding.
Improving outcomes in single chamber leadless pacemakers: strategies for minimizing vascular complications
Authors: Kouranloo Koushan , Lawson Joanne , Goode Angelic , Goode Grahame , Abozguia Khalid
Published: December 2023

Background

Leadless pacemaker therapy is associated with a significant reduction in lead-related complication rate compared to conventional transvenous single chamber pacemaker therapy. However, a significant complication rate of 1.2% was observed in vascular access due to the use of large delivery femoral sheath (27Fr). The aim of this study was to evaluate the effectiveness of real-time ultrasound guidance and Z suture technique in reducing total and major vascular complications in leadless pacemaker therapy.

Method

In this study, we performed a retrospective and prospective analysis of all adverse events associated with leadless pacemaker (Micra) implantation by two operators at a single tertiary center from December 2016 to December 2018. To mitigate the risk of vascular complications, all patients underwent real-time ultrasound-guided venipuncture for vascular access, as well as the application of a Z-suture technique for hemostasis at the end of the procedure. Data were collected on implant indications, implant procedure details, complications, and follow-up information.

Results

In this study, 45 patients with an age range of 24 to 94 years (mean 76 ± 14 years) were recruited, with 21 (46.6%) being female. The pacing indications for the patients included atrial fibrillation (24, 53.3%), vascular (7, 15.5%), infection (9, 20%), cognitive/frailty (3, 6.6%), and occupational (2, 4.4%). The implant procedures were performed under general anesthesia in 6 (13.3%) of the cases, and under local anesthesia and sedation in 39 (86.6%) of the cases. A single deployment was achieved in 43 (95.5%) of the patients, while 2 deployments were required in 2 (4.4%) of the patients. Notably, no vascular or major complications were reported in our cohort of patients.

Conclusions

The results of this observational study indicate that incorporating real-time ultrasound guidance during venipuncture and the use of a Z-suture technique significantly reduce the occurrence of both total and major vascular complications associated with the implantation of leadless pacemaker. However, more robust and larger studies are required in order to confirm these results and implications for clinical practice.
Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study
Authors: Wang Grace Hsin-Min , Chen Wei-Han , Chang Shao-Hsuan , Zhang Tianxiao , Shao Hui , Guo Jingchuan , Lo-Ciganic Wei-Hsuan
Published: December 2023

Background

Prior studies suggested that antidepressant use is associated with an increased risk of dementia compared to no use, which is subject to confounding by indication. We aimed to compare the dementia risk among older adults with depression receiving first-line antidepressants (i.e., SSRI/SNRI) versus psychotherapy, which is also considered the first-line therapy for depression.

Methods

This retrospective cohort study was conducted using the US Medical Expenditure Panel Survey from 2010 to 2019. We included adults aged ≥ 50 years diagnosed with depression who initiated SSRI/SNRI or psychotherapy. We excluded patients with a dementia diagnosis before the first record of SSRI/SNRI use or psychotherapy. The exposure was the patient’s receipt of SSRI/SNRI (identified from self-report questionnaires) or psychotherapy (identified from the Outpatient Visits or Office-Based Medical Provider Visits files). The outcome was a new diagnosis of dementia within 2 years (i.e., survey panel period) identified using ICD-9/ICD-10 codes from the Medical Conditions file. Using a multivariable logistic regression model, we reported adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We also conducted subgroup analyses by patient sex, age group, race/ethnicity, severity of depression, combined use of other non-SSRI/SNRI antidepressants, and presence of underlying cognitive impairment.

Results

Among 2,710 eligible patients (mean age = 61 ± 8, female = 69%, White = 84%), 89% used SSRIs/SNRIs, and 11% received psychotherapy. The SSRI/SNRI users had a higher crude incidence of dementia than the psychotherapy group (16.4% vs. 11.8%), with an aOR of 1.36 (95% CI = 1.06–1.74). Subgroup analyses yielded similar findings as the main analyses, except no significant association for patients who were aged < 65 years (1.23, 95% CI = 0.93–1.62), male (1.34, 95% CI = 0.95–1.90), Black (0.76, 95% CI = 0.48–1.19), had a higher PHQ-2 (1.39, 95% CI = 0.90–2.15), and had underlying cognitive impairment (1.06, 95% CI = 0.80–1.42).

Conclusions

Our findings suggested that older adults with depression receiving SSRIs/SNRIs were associated with an increased dementia risk compared to those receiving psychotherapy.
Stakeholders’ experiences of comprehensive geriatric assessment in an inpatient hospital setting: a qualitative systematic review and meta-ethnography
Authors: O’Shaughnessy Íde , Fitzgerald Christine , Hayes Christina , Leahy Aoife , O’Connor Margaret , Ryan Damien , Shchetkovsky Denys , Steed Fiona , Carey Leonora , Quinn Colin , Shanahan Elaine , Galvin Rose , Robinson Katie
Published: December 2023

Background

Comprehensive geriatric assessment (CGA) is considered the gold standard approach to improving a range of outcomes for older adults living with frailty admitted to hospital. To date, research has predominantly focused on quantitative syntheses of the international evidence with limited focus on qualitative synthesis of stakeholder perspectives. This review aims to resolve this research gap by identifying and synthesising qualitative studies reporting multiple stakeholders’ experiences of inpatient CGA.

Methods

A systematic search of five electronic databases was conducted. Qualitative or mixed methods studies that included qualitative findings on the experiences of CGA in an inpatient hospital setting from the perspective of healthcare professionals (HCP), older adults, and those important to them were included. The protocol was registered on PROSPERO (Registration: CRD42021283167) and the 10-item Critical Appraisal Skills Programme checklist was used to appraise the methodological quality of included studies. Results were synthesised as a meta-ethnography.

Results

Eleven studies, which reported on the experiences of 153 HCPs, 91 older adults and 57 caregivers were included. The studies dated from 2011 to 2021 and three key themes were identified: (1) HCPs, older adults and caregivers report conflicting views on CGA as a holistic process, (2) most HCPs, but only some older adults and caregivers view CGA goalsetting and care planning as collaborative, and (3) all stakeholders value care continuity during the transition from hospital to home but often fail to achieve it.

Conclusion

While HCPs, older adults, and caregivers’ values and ambitions related to CGA broadly align, their experiences often differ. The identified themes highlight organisational and relational factors, which positively and negatively influence CGA practices and processes in an inpatient hospital setting.
Potentially inappropriate medications among older patients with Parkinson’s disease: a cross-sectional analysis of a national health insurance database in China
Authors: Fu Mengyuan , Li Can , Zhao Zinan , Ling Kexin , Gong Zhiwen , Li Huangqianyu , Li Ting , Li Jianchun , Cao Weihang , Hu Xin , Shi Luwen , Jin Pengfei , Guan Xiaodong
Published: December 2023

Background

With the rapid aging trend of China's population, the issue of drug rational use in older adults has become more and more prominent. Parkinson’s disease (PD) is the one of the most common age-related neurodegenerative disorders. Pharmaceutical treatment plays a cardinal role in alleviating motor and non-motor symptoms to improve the quality of life of patients with PD. Patients with PD have complex medical needs yet little is known about the use of potentially inappropriate medications (PIM) among them in China. We quantify the prevalence of PIM use and identify its predictors among older persons with PD in China.

Methods

We conducted a cross-sectional analysis using a national representative database of all medical insurance beneficiaries across China, extracting records of ambulatory visits of older adults with PD between 2015 and 2017. Beneficiaries aged 65 and above were eligible for inclusion. The prevalence of patients exposed to overall PIMs and PIMs related to motor and cognitive impairment was calculated based on Beers Criteria 2015 version. Potential predictors of PIM concerning patients’ characteristics were estimated using multivariate logistic regression.

Results

A total of 14,452 older adults with PD were included. In total, 8,356 (57.8%) patients received at least one PIM; 2,464 (17.1%) patients received at least one motor-impairing PIM and 6,201 (42.9%) patients received at least one cognition-impairing PIM. The prevalence of overall PIM use was higher in patients of older age group (54.7% [65–74] vs. 59.5% [75–84; OR, 1.22; 95% CI, 1.14–1.31] vs.65.5% [≥ 85; OR, 1.58; 95% CI, 1.38–1.80) and females (61.4% [female] vs. 55.0% [males; OR, 0.77; 95% CI, 0.72–0.82).

Conclusions

Prescribing PIMs for older adults with PD was common in China, especially for females and older age groups, yet younger patients were more inclined to be prescribed with motor or cognition-impaired PIMs. Our findings represent a clear target awaiting multidimensional efforts to promote the rational prescribing of medications for this vulnerable population.
A randomized, double-blinded, placebo-controlled clinical trial of sterile filtered human amniotic fluid for treatment of COVID-19
Authors: Tonna Joseph E. , Pierce Jan , Brintz Benjamin J. , Bardsley Tyler , Hatton Nathan , Lewis Giavonni , Phillips John D. , Skidmore Chloe R. , Selzman Craig H.
Published: December 2023

Importance

Acellular human amniotic fluid (hAF) is an antimicrobial and anti-inflammatory fluid that has been used to treat various pro-inflammatory conditions. In a feasibility study, we have previously demonstrated that hAF could be safely administered to severely ill patients with coronavirus disease-19 (COVID-19). The impact of acellular hAF on markers of systemic inflammation and clinical outcomes during COVID-19 infection remain unknown.

Objective

To determine the safety and efficacy of acellular, sterile processed intravenously administered hAF on markers of systemic inflammation during COVID-19.

Design, settings and participants

This single-center Phase I/II randomized, placebo controlled clinical trial enrolled adult (age ≥ 18 years) patients hospitalized for respiratory symptoms of COVID-19, including hypoxemia, tachypnea or dyspnea. The study was powered for outcomes with an anticipated enrollment of 60 patients. From 09/28/2020 to 02/04/2022 we enrolled and randomized 47 (of an anticipated 60) patients hospitalized due to COVID-19. One patient withdrew consent after randomization but prior to treatment. Safety outcomes to 30 days were collected through hospital discharge and were complete by the end of screening on 6/30/2022.

Interventions

Intravenous administration of 10 cc sterile processed acellular hAF once daily for up to 5 days vs placebo.

Main outcome and measures

Blood biomarkers of inflammation, including C-Reactive protein (CRP), lactate dehydrogenase, D-dimer, and interleukin-6 (IL-6), as well as safety outcomes.

Results

Patients who were randomized to hAF (n = 23) were no more likely to have improvements in CRP from baseline to Day 6 than patients who were randomized to placebo (n = 24) hAF: -5.9 [IQR -8.2, -0.6] vs placebo: -5.9 [-9.4, -2.05]; p = 0.6077). There were no significant differences in safety outcomes or adverse events. Secondary measures of inflammation including lactate dehydrogenase, D-dimer and IL-6 were not statistically different from baseline to day 6.

Conclusions and relevance

In this randomized clinical trial involving hospitalized patients with COVID-19, the intravenous administration of 10 cc of hAF daily for 5 days did not result in statistically significant differences in either safety or markers of systemic inflammation compared to placebo, though we did not achieve our enrollment target of 60 patients.

Trial registration

This trial was registered at ClinicalTrials.gov as #NCT04497389 on 04/08/2020.
Value of inversion imaging to diagnosis in differentiating malignant from benign breast masses
Authors: Li Na , Hou Zhongguang , Wang Jiajia , Bi Yu , Wu Xiabi , Zhan Yunyun , Peng Mei
Published: December 2023

Background

We aimed to evaluate the added value of inversion imaging in differentiating between benign and malignant breast masses when combined with the Breast Imaging Reporting and Data System (BI-RADS).

Methods

A total of 364 patients with 367 breast masses (151 benign and 216 malignant) who underwent conventional ultrasound and inversion imaging prior to breast surgery were included. A 5-point inversion score (IS) scale was proposed based on the masses’ internal echogenicity and distribution characteristics in the inversion images. The combination of IS and BI-RADS was compared with BI-RADS alone to evaluate the value of inversion imaging for breast mass diagnosis. The diagnostic performance of the BI-RADS and its combination with IS for breast masses were analyzed using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Results

The IS for malignant breast masses (3.96 ± 0.77) was significantly higher than benign masses (2.58 ± 0.98) (P < 0.001). The sensitivity, specificity, accuracy, PPV, and NPV of BI-RADS were 86.1%, 81.5%, 84.2%, 86.9%, and 80.4%, respectively, and an AUC was 0.909. By compared with BI-RADS, 72 breast masses were downgraded from suspected malignancy to benign, and 6 masses were upgraded from benign to suspected malignancy. Thus, the specificity was increased from 81.5 to 84.8%, it allows 72 benign masses avoid biopsy.

Conclusion

The combination of inversion imaging with BI-RADS can effectively improve the diagnostic efficacy of breast masses, and inversion imaging could help benign masses avoid biopsy.
A differential diagnosis between uterine leiomyoma and leiomyosarcoma using transcriptome analysis
Authors: Kim Kidong , Kim Sarah , Ahn TaeJin , Kim Hyojin , Shin So-Jin , Choi Chel Hun , Park Sungmin , Kim Yong-Beom , No Jae Hong , Suh Dong Hoon
Published: December 2023

Background

The objective of this study was to estimate the accuracy of transcriptome-based classifier in differential diagnosis of uterine leiomyoma and leiomyosarcoma. We manually selected 114 normal uterine tissue and 31 leiomyosarcoma samples from publicly available transcriptome data in UCSC Xena as training/validation sets. We developed pre-processing procedure and gene selection method to sensitively find genes of larger variance in leiomyosarcoma than normal uterine tissues. Through our method, 17 genes were selected to build transcriptome-based classifier. The prediction accuracies of deep feedforward neural network (DNN), support vector machine (SVM), random forest (RF), and gradient boosting (GB) models were examined. We interpret the biological functionality of selected genes via network-based analysis using GeneMANIA. To validate the performance of trained model, we additionally collected 35 clinical samples of leiomyosarcoma and leiomyoma as a test set (18 + 17 as 1st and 2nd test sets).

Results

We discovered genes expressed in a highly variable way in leiomyosarcoma while these genes are expressed in a conserved way in normal uterine samples. These genes were mainly associated with DNA replication. As gene selection and model training were made in leiomyosarcoma and uterine normal tissue, proving discriminant of ability between leiomyosarcoma and leiomyoma is necessary. Thus, further validation of trained model was conducted in newly collected clinical samples of leiomyosarcoma and leiomyoma. The DNN classifier performed sensitivity 0.88, 0.77 (8/9, 7/9) while the specificity 1.0 (8/8, 8/8) in two test data set supporting that the selected genes in conjunction with DNN classifier are well discriminating the difference between leiomyosarcoma and leiomyoma in clinical sample.

Conclusion

The transcriptome-based classifier accurately distinguished uterine leiomyosarcoma from leiomyoma. Our method can be helpful in clinical practice through the biopsy of sample in advance of surgery. Identification of leiomyosarcoma let the doctor avoid of laparoscopic surgery, thus it minimizes un-wanted tumor spread.
Effects of different interventions on internet addiction: a systematic review and network meta-analysis
Authors: Zhu Yuqiong , Chen Haihan , Li Junda , Mei Xian , Wang Wenjuan
Published: December 2023

Background

Globally, Internet is a recognized form of leisure, but there are growing apprehensions about the increasing number of individuals developing an addiction to it. Recent research has focused on social issues associated with internet addiction (IA). However, the treatment of IA is currently unclear. This study aimed to explore the relationship between IA treatment outcomes and different intervention strategies through systematic review and data analysis of patients who received different intervention modes.

Methods

A meta-analysis was conducted using RevMan 5.4 and Stata 14.2 on 57 literature research data from five Chinese and English databases, PubMed, Embase, Web of Science, Wanfang and CNKI.

Result

A total of 57 randomized controlled trials (RCTs) were included in this network meta-analysis involving 3538 IA patients and 13 different interventions. The network meta-analysis results demonstrated that the top four interventions were: rTMS + CBT, drug + others, rTMS, and electro-acupuncture + CBT.

Conclusion

Our study indicated that comprehensive therapy had an optimal therapeutic effect on IA patients and rTMS + CBT ranked first among all therapeutic indicators of intervention, indicating optimal clinical effectiveness.
Effects of brief cognitive behavioral therapy on mental health in substance-related disorder: a randomized controlled trial
Authors: Alavi Seyed Mohammad Amin , Irani Reza Davasaz , Fattahi Payam , Pakseresht Sirus
Published: December 2023

Background & objectives

Population and aging are major contributing factors influencing the increase in substance use disorder (SUD), which in itself affects mental health, particularly anxiety and depression. Cognitive behavioral therapy (CBT) and pharmacotherapy co-treatment are considered the gold standard for the treatment of SUD. Thus, the present study has been carried out to investigate the efficacy of brief CBT on the general health of opioid users.

Methods

A randomized controlled trial (RCT) was conducted with forty opioid users whose addiction was dully confirmed by a psychiatrist at the drop-in center of the Ahvaz Jundishapur University of Medical Sciences. The patients were then randomly divided into two equal groups (n = 20). The control group was treated solely using methadone maintenance therapy (MMT); however, the intervention group underwent four sessions of CBT in addition to MMT. The general health questionnaire (GHQ) consisting of 28 items (Goldberg, 1979) was applied to both groups at the beginning and end of the study. The collected data was analyzed using IBM SPSS ver. 26, and data analysis was carried out using chi-square, t-test, Mann-Whitney, and Poisson regression model. P < 0.05 was statistically significant for all the aforementioned tests.

Results

The mean age for the control and intervention groups were 37.95 ± 7.64 and 43.85 ± 9.92, respectively (p = 0.042). There was no statistically significant difference in terms of gender and levels of education (p = 0.311 and p = 0.540). Both groups differed statistically regarding marital status and occupation (p = 0.025 and 0.002). There was no significant statistical difference in all subclasses and the total scores of GHQ-28 for both groups, except for anxiety and insomnia in the intervention group (p = 0.038). After applying a Likert scale with a 23-point cut-off score, there was no statistically significant difference in terms of psychosis after intervention in the intervention group (p = 0.077).

Conclusion

The results of the current study show that brief CBT is effective on psychiatric health, especially anxiety and sleep disorders, whereas brief CBT fails to affect the patient’s depression, somatic symptoms, and social dysfunction.

Trial registration

The Iranian Registry of Clinical Trials (IRCT) approved the study design (IRCT registration number: IRCT20190929044917N1, registration date: 13/01/2020).