Evolving role of the health system CIO: perspectives from 33 health systems.

OBJECTIVES: This study explores the evolving position of the health system chief information officer (CIO) by identifying new core roles for success. METHODS: An advisory board of industry executives and system leaders guided the study. Purposeful sampling was used to invite chief executive officer and CIOs from 65 not-for-profit US health systems to participate. Interviews were conducted with 51 executives from 33 different systems, using a comprehensive interview topic guide. Interview transcripts were analysed using NVivo software, focusing on themes related to the evolving role of the health system CIO. RESULTS: Analyses revealed three main themes, with the CIO as (1) enabler of strategic change and transformation, (2) strategic developer of technology and leadership talent and (3) driver of organisational culture. DISCUSSION: The role of CIO has undergone transformation from technology and information system management to strategic leadership within the broader health system context. It highlights the importance of comprehensive business knowledge for CIOs and the need for other C-suite executives to have a deeper understanding of information and technology. CONCLUSION: As healthcare continues to evolve, the role of the CIO is expected to expand further, requiring a blend of technical and strategic business skills. This evolution presents opportunities for health systems to enhance their leadership development programmes, preparing leaders for the complexities of the contemporary health system sector.

Investigating the Immune-Stimulating Potential of ß-Glucan from Aureobasidium pullulans in Cancer Immunotherapy.

ß-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified soluble ß-1,3/1,6-glucan derived from Aureobasidium pullulans. The refined PPTEE-glycan demonstrated robust immune stimulation in vitro, activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo, promoting antigen-specific antibodies and CD8+ T cell proliferation. Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans-derived ß-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.

A novel treatment strategy targeting cellular pathways with natural products to alleviate sarcopenia.

Sarcopenia is a condition marked by a significant reduction in muscle mass and strength, primarily due to the aging process, which critically impacts muscle protein dynamics, metabolic functions, and overall physical functionality. This condition leads to increased body fat and reduced daily activity, contributing to severe health issues and a lower quality of life among the elderly. Recognized in the ICD-10-CM only in 2016, sarcopenia lacks definitive treatment options despite its growing prevalence and substantial social and economic implications. Given the aging global population, addressing sarcopenia has become increasingly relevant and necessary. The primary causes include aging, cachexia, diabetes, and nutritional deficiencies, leading to imbalances in protein synthesis and degradation, mitochondrial dysfunction, and hormonal changes. Exercise remains the most effective intervention, but it is often impractical for individuals with limited mobility, and pharmacological options such as anabolic steroids and myostatin inhibitors are not FDA-approved and are still under investigation. This review is crucial as it examines the potential of natural products as a novel treatment strategy for sarcopenia, targeting multiple mechanisms involved in its pathogenesis. By exploring natural products' multi-targeted effects, this study aims to provide innovative and practical solutions for sarcopenia management. Therefore, this review indicates significant improvements in muscle mass and function with the use of specific natural compounds, suggesting promising alternatives for those unable to engage in regular physical activity.

Combination of rituximab and methotrexate followed by rituximab and cytarabine in elderly patients with primary central nervous system lymphoma.

The optimal treatment strategy for newly diagnosed primary central nervous system lymphoma (PCNSL) has yet to be established, especially in the elderly. In the current study, we conducted a phase II study to evaluate the efficacy and safety of rituximab plus high-dose MTX followed by rituximab plus cytarabine in patients aged ≥60 years newly diagnosed with PCNSL. Patients received an induction treatment of high-dose methotrexate plus rituximab followed by two cycles of a consolidation treatment of cytarabine plus rituximab. The primary end-point was a 2-year progression-free survival (PFS) rate. A total of 35 patients were recruited, and their median age was 73 (range: 60-81). After induction treatment, the complete and partial responses (PRs) were 56% and 20% respectively. Twenty-six patients proceeded to the consolidation treatment; the complete and PRs were 59% and 9% respectively. After a median follow-up duration of 36.0 months, the 2-year PFS rate was 58.7%. Treatment was generally well-tolerated as only three patients were withdrawn from the study due to toxicity, and no treatment-related mortality was reported. The 2-year overall survival rate was 77.9%. The current study may suggest the feasibility of administering high-dose MTX plus cytarabine in PCNSL patients aged ≥60 years and the potential role of additive rituximab.

Intravascular Casting Radiopaque Hydrogel Systems for Transarterial Chemo/Cascade Catalytic/Embolization Therapy of Hepatocellular Carcinoma.

This paper introduces catheter-directed intravascular casting hydrogels for transarterial chemo/starvation/chemodynamic embolization (TACSCE) therapy of hepatocellular carcinoma (HCC). Comprising Mn ion-crosslinked hyaluronic acid-dopamine (HD) with glucose oxidase (for glucose decomposition to H2O2 in starvation therapy), doxorubicin (for chemotherapy), and iopamidol (for X-ray imaging), these hydrogels are fabricated for transarterial embolization therapy guided by X-ray fluoroscopy. Mn4+ (from MnO2) demonstrates strong coordination with the catechol group of HD, providing hypoxia relief through O2 generation and cellular glutathione (GSH) consumption, compared to the OH radical generation potential of Mn2+. The gelation time-controlled, catheter-injectable, and rheologically tuned multitherapeutic/embolic gel system effectively reaches distal arterioles, ensuring complete intravascular casting with fewer complications related to organic solvents. Glucose deprivation, cascade reactive oxygen species (ROS) generation, GSH depletion, and sustained release profiles of multiple drug cargos from the hydrogel system are also achieved. The combined chemo/starvation/chemodynamic efficacies of these designed hydrogel systems are confirmed in HCC cell cultures and HCC-bearing animal models. The developed radiopaque/injectable/embolic/sol-to-gel transformable systems for TACSCE therapy may offer enhanced therapeutic efficacies compared to typical transarterial embolization and transarterial chemoembolization procedures for HCC.

Financial Benefits of Renal Dose-Adjusted Dipeptidyl Peptidase-4 Inhibitors for Patients with Type 2 Diabetes and Chronic Kidney Disease.

Background: Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes. Methods: This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models. Results: In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m2, respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m2 and 30.4% for eGFR <30 mL/min/1.73 m2. According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity. Conclusion: Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.

The expression of PD-L1 on tumor-derived exosomes enhances infiltration and anti-tumor activity of αCD3 × αPD-L1 bispecific antibody-armed T cells.

Anti-cluster of differentiation (CD) 3 × α programmed death-ligand 1 (PD-L1) bispecific T-cell engager (BsTE)-bound T-cells (BsTE:T) are a promising new cancer treatment agent. However, the mechanisms of action of bispecific antibody-armed activated T-cells are poorly understood. Therefore, this study aimed to investigate the anti-tumor mechanism and efficacy of BsTE:T. The BsTE:T migration was assessed in vivo and in vitro using syngeneic and xenogeneic tumor models, flow cytometry, immunofluorescence staining, transwell migration assays, microfluidic chips, Exo View R100, western blotting, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology. In murine B16 melanoma, MC38 colon cancer, and human multiple myeloma cells, BsTE:T exhibited superior tumor elimination relative to that of T-cells or BsTE alone. Moreover, BsTE:T migration into tumors was significantly enhanced owing to the presence of PD-L1 in tumor cells and secretion of PD-L1-containing exosomes. Furthermore, increased infiltration of CD44highCD62Llow effector memory CD8+ T-cells into tumors was closely associated with the anti-tumor effect of BsTE:T. Therefore, BsTE:T is an innovative potential anti-tumor therapy, and exosomal PD-L1 plays a crucial role both in vitro and in vivo in the anti-tumor activity of BsTE:T.

Impact of COVID-19 on brain connectivity and rehabilitation outcome after stroke.

Background: Coronavirus disease (COVID-19) may induce neurological issues, impacting brain structure and stroke recovery. Limited studies have explored its effects on post-stroke rehabilitation. Our study compares brain structure and connectivity, assessing rehabilitation outcomes based on pre-stroke COVID-19 infection. Methods: A retrospective analysis of 299 post-stroke rehabilitation cases from May 2021 to January 2023 included two groups: those diagnosed with COVID-19 at least two weeks before stroke onset (COVID group) and those without (control group). Criteria involved first unilateral supratentorial stroke, <3 months post-onset, initial MR imaging, and pre- and post-rehabilitation clinical assessments. Propensity score matching ensured age, sex, and initial clinical assessment similarities. Using lesion mapping, tract-based statistical analysis, and group-independent component analysis MRI scans were assessed for structural and functional differences. Results: After propensity score matching, 12 patients were included in each group. Patient demographics showed no significant differences. Analyses of MR imaging revealed no significant differences between COVID and control groups. Post-rehabilitation clinical assessments improved notably in both groups, however the intergroup analysis showed no significant difference. Conclusions: Previous COVID-19 infection did not affect brain structure or connectivity nor outcomes after rehabilitation.

Chromatin remodeling-driven autophagy activation induces cisplatin resistance in oral squamous cell carcinoma.

It is still challenging to predict the efficacy of cisplatin-based therapy, particularly in relation to the activation of macroautophagy/autophagy in oral squamous cell carcinoma (OSCC). We studied the effect of selected chromatin remodeling genes on the cisplatin resistance and their interplay with autophagy in 3-dimensional tumor model and xenografts. We analyzed gene expression patterns in the cisplatin-sensitive UMSCC1, and a paired cisplatin-resistant UM-Cis cells. Many histone protein gene clusters involved in nucleosome assembly showed significant difference of expression. Gain- and loss-of-function analyses revealed an inverse correlation between cisplatin resistance and HIST1H3D expression, while a positive correlation was observed with HIST3H2A or HIST3H2B expression. In UM-Cis, HIST3H2A- and HIST3H2B-mediated chromatin remodeling upregulates autophagy status, which results in cisplatin resistance. Additionally, knockdown of HIST3H2A or HIST3H2B downregulated autophagy-activating genes via chromatin compaction of their promoter regions. MiTF, one of the key autophagy regulators upregulated in UM-Cis, negatively regulated transcription of HIST1H3D, suggesting an interplay between chromatin remodeling-dependent cisplatin resistance and autophagy. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, protein expression pattern of the selected histone protein genes were matched with the in vitro data. By examining the relationship between autophagy and chromatin remodeling genes, we identified a set of candidate genes with potential use as markers predicting chemoresistance in OSCC biopsy samples.

Pre-procedural nursing home length of stay and outcomes of transcatheter aortic valve replacement.

BACKGROUND: Older adults with severe aortic stenosis (AS) may receive care in a nursing home (NH) prior to undergoing transcatheter aortic valve replacement (TAVR). NH level of care can be used to stabilize medical conditions, to provide rehabilitation services, or for long-term care services. Our primary objective is to determine whether NH utilization pre-TAVR can be used to stratify patients at risk for higher mortality and poor disposition outcomes at 30 and 365 days post-TAVR. METHODS: We conducted a retrospective cohort study among Medicare beneficiaries who spent ≥1 day in an NH 6 months before TAVR (2011-2019). The intensity of NH utilization was categorized as low users (1-30 days), medium users (31-89 days), long-stay NH residents (≥ 100 days, with no more than a 10-day gap in care), and high post-acute rehabilitation patients (≥90 days, with more than a 10-day gap in care). The probabilities of death and disposition were estimated using multinomial logistic regression, adjusting for age, sex, and race. RESULTS: Among 15,581 patients, 9908 (63.6%) were low users, 4312 (27.7%) were medium users, 663 (4.3%) were high post-acute care rehab users, and 698 (4.4%) were long-stay NH residents before TAVR. High post-acute care rehabilitation patients were more likely to have dementia, weight loss, falls, and extensive dependence of activities of daily living (ADLs) as compared with low NH users. Mortality was the greatest in high post-acute care rehab users: 5.5% at 30 days, and 36.4% at 365 days. In contrast, low NH users had similar mortality rates compared with long-stay NH residents: 4.8% versus 4.8% at 30 days, and 24.9% versus 27.0% at 365 days. CONCLUSION: Frequent bouts of post-acute rehabilitation before TAVR were associated with adverse outcomes, yet this metric may be helpful to determine which patients with severe AS could benefit from palliative and geriatric services.

Induction of Cell Death by Bifidobacterium infantis DS1685 in Colorectal and Breast Cancers via SMAD4/TGF-Beta Activation.

Therapeutic advancements in treatments for cancer, a leading cause of mortality worldwide, have lagged behind the increasing incidence of this disease. There is a growing interest in multifaceted approaches for cancer treatment, such as chemotherapy, targeted therapy, and immunotherapy, but due to their low efficacy and severe side effects, there is a need for the development of new cancer therapies. Recently, the human microbiome, which is comprised of various microorganisms, has emerged as an important research field due to its potential impact on cancer treatment. Among these microorganisms, Bifidobacterium infantis has been shown to significantly improve the efficacy of various anticancer drugs. However, research on the role of B. infantis in cancer treatment remains insufficient. Thus, in this study, we explored the anticancer effect of treatment with B. infantis DS1685 supernatant (BI sup) in colorectal and breast cancer cell lines. Treatment with BI sup induced SMAD4 expression to suppress cell growth in colon and breast cancer cells. Furthermore, a decrease in tumor cohesion was observed through the disruption of the regulation of EMT-related genes by BI sup in 3D spheroid models. Based on these findings, we anticipate that BI sup could play an adjunctive role in cancer therapy, and future cotreatment of BI sup with various anticancer drugs may lead to synergistic effects in cancer treatment.

Three-Dimensional Integrated Synaptic Devices Based on a Silver-Cluster Conduction Mechanism with High Thermostability.

During the operation of synaptic devices based on traditional conductive filament (CF) models, the formation and dissolution of CFs are usually uncertain. Moreover, when the device is operated for a long time, the CFs may dissolve due to both the Joule heat generated by the device itself and the thermal coupling between the devices. These problems seriously reduce the reliability and stability of the synaptic device. Here, an artificial synapse device based on polyimide-molybdenum disulfide quantum dot (MoS2 QD) nanocomposites is presented. Research has shown that MoS2 QDs doped into the active layer can effectively induce the reduction of Ag ions into Ag atoms, leading to the formation of Ag clusters and thereby achieving control over the growth of the CFs. Therefore, the device is capable of stably realizing various basic synaptic functions. Moreover, the long-term potentiation/long-term depression (LTP/LTD) of this device shows good linearity. In addition, due to the change in the shape of the CFs, the highly integrated devices with a three-dimensional (3D) stacked structure can operate normally even in a high-temperature environment of 110 °C. Finally, the synaptic characteristics of the devices on learning and inference tests show that their recognition rates are approximately 90.75% (room temperature) and 90.63% (110 °C).

Enhancing the cytotoxicity of immunotoxins by facilitating their dissociation from target receptors under the reducing conditions of the endocytic pathway.

Immunotoxins (ITs) are recombinant chimeric proteins that combine a protein toxin with a targeting moiety to facilitate the selective delivery of the toxin to cancer cells. Here, we present a novel strategy to enhance the cytosolic access of ITs by promoting their dissociation from target receptors under the reducing conditions of the endocytic pathway. We engineered monobodySS, a human fibronectin type III domain-based monobody with disulfide bond (SS)-containing paratopes, targeting receptors such as EGFR, EpCAM, Her2, and FAP. MonobodySS exhibited SS-dependent target receptor binding with a significant reduction in binding under reducing conditions. We then created monobodySS-based ITs carrying a 25 kDa fragment of Pseudomonas exotoxin A (PE25), termed monobodySS-PE25. These ITs showed dose-dependent cytotoxicity against target receptor-expressing cancer cells and a wider therapeutic window due to higher efficacy at lower doses compared to controls with SS reduction inhibited. ERSS/28-PE25, with a KD of 28 nM for EGFR, demonstrated superior tumor-killing potency compared to ER/21-PE25, which lacks an SS bond, at equivalent and lower doses. In vivo, ERSS/28-PE25 outperformed ER/21-PE25 in suppressing tumor growth in EGFR-overexpressing xenograft mouse models. This study presents a strategy for developing solid tumor-targeting ITs using SS-containing paratopes to enhance cytosolic delivery and antitumor efficacy.

Highly Conductive and Stretchable Hydrogel Nanocomposite Using Whiskered Gold Nanosheets for Soft Bioelectronics.

The low electrical conductivity of conductive hydrogels limits their applications as soft conductors in bioelectronics. This low conductivity originates from the high water content of hydrogels, which impedes facile carrier transport between conductive fillers. This study presents a highly conductive and stretchable hydrogel nanocomposite comprising whiskered gold nanosheets. A dry network of whiskered gold nanosheets is fabricated and then incorporated into the wet hydrogel matrices. The whiskered gold nanosheets preserve their tight interconnection in hydrogels despite the high water content, providing a high-quality percolation network even under stretched states. Regardless of the type of hydrogel matrix, the gold-hydrogel nanocomposites exhibit a conductivity of ≈520 S cm-1 and a stretchability of ≈300% without requiring a dehydration process. The conductivity reaches a maximum of ≈3304 S cm-1 when the density of the dry gold network is controlled. A gold-adhesive hydrogel nanocomposite, which can achieve conformal adhesion to moving organ surfaces, is fabricated for bioelectronics demonstrations. The adhesive hydrogel electrode outperforms elastomer-based electrodes in in vivo epicardial electrogram recording, epicardial pacing, and sciatic nerve stimulation.

Validation of Claims-Based Frailty Index for Identifying Moderate-to-Severe Dementia in Medicare Beneficiaries.

OBJECTIVE: Previous research using the National Health and Aging Trends Study showed that a claims-based frailty index (CFI) could be useful for identifying moderate-to-severe dementia in Medicare claims data. This study aims to validate the findings in an independent cohort. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: The study included 658 fee-for-service beneficiaries with dementia who participated in the 2016-2020 Medicare Current Beneficiary Survey in the community-dwelling. METHODS: We operationalized the Functional Assessment Staging Test (FAST) scale (range: 1-7, stages 5-7 indicate moderate-to-severe dementia) using survey information. CFI (range: 0-1, higher scores indicate greater frailty) was calculated using Medicare claims 12 months before the participants' interview date. Using the previously proposed cut point of 0.280, we calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying moderate-to-severe dementia. Survey procedures were used to account for survey design and weighted to reflect national estimates. RESULTS: The population had a mean age (SD) of 80.7 (8.9) years, 58.5% female, and 101 beneficiaries (14.8%) had moderate-to-severe dementia. The CFI cut point of 0.280 demonstrated sensitivity 0.49 (95% CI, 0.38-0.59), specificity 0.80 (0.77-0.84), PPV 0.30 (0.23-0.38), and NPV 0.90 (0.87-0.93). Compared with those with a CFI <0.280, beneficiaries with a CFI ≥0.280 had an elevated risk of mortality (2.9% vs 4.1%) over 1 year. CONCLUSIONS AND IMPLICATIONS: These results confirm our previous findings that CFI among beneficiaries with a dementia diagnosis is a useful measure of moderate-to-severe dementia for Medicare claims data.

Learning curve analysis for hand-assisted laparoscopic living donor nephrectomy: an analysis of 96 consecutive cases performed by a trained gastrointestinal surgeon.

Purpose: This study aims to analyze the learning curve of hand-assisted laparoscopic living donor nephrectomy (HLDN) conducted by a trained gastrointestinal surgeon. Methods: A retrospective analysis was performed on the perioperative clinical data of 96 consecutive patients who underwent HLDN from May 2013 to March 2023. The learning curve was evaluated using the cumulative sum (CUSUM) test based on operation time and risk-adjusted CUSUM for postoperative complications. Patients were divided into three groups (novice, development, and competency phases) based on changes in operation time. Patient demographics and perioperative outcomes were compared between each group. Results: Among the patients, 35 were male, with a mean age of 48.9 ± 11.3 years and a mean body mass index (BMI) of 24.5 ± 3.2 kg/m2. The novice phase (phase 1) included the first 30 cases, with the development phase (phase 2) up to the 65th case. Operation times were significantly different across phases, averaging 263.2 ± 33.4, 211.1 ± 34.4, and 161.1 ± 31.3 minutes for phases 1, 2, and 3, respectively (P < 0.001). Blood loss decreased gradually across phases (phase 1, 264.7 ± 144.4 mL; phase 2, 239.7 ± 166.3 mL; phase 3, 198.8 ± 103.5 mL), though not statistically significant. BMI impacted operation time only in phase 1. Overall postoperative complications occurred in 13 cases (Clavien-Dindo grade I, 4 cases; grade II, 9 cases), with no significant differences across phases. Conclusion: HLDN can be safely performed by a trained gastrointestinal surgeon, with approximately 30 cases needed to achieve proficiency.