Lessons learned from a multi-site collaborative working toward a digital health use screening tool.

Digital health has the potential to expand health care and improve outcomes for patients-particularly for those with challenges to accessing in-person care. The acceleration of digital health (and particularly telemedicine) prompted by the Coronavirus-19 (COVID-19) pandemic facilitated continuity of care in some settings but left many health systems ill-prepared to address digital uptake among patients from underserved backgrounds, who already experience health disparities. As use of digital health grows and the digital divide threatens to widen, healthcare systems must develop approaches to evaluate patients' needs for digital health inclusion, and consequentially equip patients with the resources needed to access the benefits of digital health. However, this is particularly challenging given the absence of any standardized, validated multilingual screening instrument to assess patients' readiness for digital healthcare that is feasible to administer in already under-resourced health systems. This perspective is structured as follows: (1) the need for digital health exclusion risk screening, (2) our convening as a group of stakeholders, (3) our review of the known digital health screening tools and our assessment, (4) formative work with patients regarding their perceptions on language and concepts in the digital health screening tools, and (5) conclusion with recommendations for digital health advocates generated by this collaborative of digital health researchers and operations leaders. There is a need to develop a brief, effective tool to screen for digital health use that can be widely implemented in diverse populations. We include lessons learned from our experiences in developing and testing risk of digital health exclusion screening questions in our respective health systems (e.g., patient perception of questions and response options). Because we recognize that health systems across the country may be facing similar challenges and questions, this perspective aims to inform ongoing efforts in developing health system digital exclusion screening tools and advocate for their role in advancing digital health equity.

Uterine torsion in pregnancy: A case report.

INTRODUCTION AND IMPORTANCE: Uterine torsion are extremely rare in pregnancy as few cases have been reported. Torsion of the pregnant uterus is defined as the rotation more than 45 degrees around the long axis of the uterus. It has been referred as, once-in-a-lifetime diagnosis by obstetricians and gynecologists. This paper reports a case of uterine torsion and velamentous cord insertion from our obstetrical practice, along with a review of reported cases. CASE PRESENTATION: The 30-year-old patient (G2P1) at 38 weeks' gestation with a singleton pregnancy, was admitted to the Obstetrical Unit with uterine cramping and decreased fetal movement. Her prior obstetrical history included one uncomplicated term Cesarean section (2016), the current pregnancy had been velamentous cord insertion at 20 weeks' gestation and intra-uterine growth restriction at the 33rd -week gestation until the presentation date. Emergency Cesarean section was performed the 90 degrees uterine torsion and was diagnosed intra-operatively. This patient and her baby recovered and were discharged home on the fifth post-operative day. CLINICAL DISCUSSION: Uterine torsion, a rare pregnancy complication, should be considered when evaluating acute abdominal pain or performing a Cesarean delivery, especially in cases of abnormal fetal presentation, pelvic adhesions, uterine fibroids, malformations, or ovarian tumors. Early diagnosis and proper treatment are crucial due to the negative prognosis for both mother and baby. CONCLUSION: Uterine torsion along with velamentous cord insertion is difficult to diagnosis due to its rarity. It is essential to focus on uterine malformations during ultrasound examinations in the first, second, and third trimesters.

Acute cancer-related symptoms and concerns among patients receiving chemotherapy: current state of the science.

PURPOSE: This study provides an updated evaluation of the prevalence and severity of acute cancer-related symptoms and quality of life (QOL) concerns among patients treated with emetogenic chemotherapy. METHODS: Patients were recruited to a larger, multi-site observational study prior to starting chemotherapy. Participants completed sociodemographic questionnaires and clinical data were abstracted via medical record review. Symptoms and QOL were assessed 5 days after starting moderately or highly emetogenic chemotherapy. Functional Assessment of Cancer Therapy - General assessed QOL concerns. Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events evaluated symptoms. Symptoms were considered severe when participants responded "severe" or "very severe." RESULTS: Participants (N = 1174) were on average 58 ± 13 years, mostly female (73%), non-Hispanic (89%), and White (87%). Most participants were diagnosed with breast (38.1%), gynecological (20%), and gastrointestinal (17.1%) cancer. The most common QOL concerns of any severity were fatigue (94%), anhedonia (89%), dissatisfaction with QOL (86%), and sleep disturbance (86%). The most common severe QOL concerns were anhedonia (44%), fatigue (40%), and inability to work (38%). Decreased appetite (74%), pain (71%), and constipation (70%) were the most common symptoms of any severity, as well as most common severe symptoms (13%, 18%, and 18%, respectively). CONCLUSION: Herein, updates are provided in regard to QOL concerns and symptoms reported by patients in the days after chemotherapy and demonstrates that concerns and symptoms have shifted in the last decade.

A Versatile Intestine-on-Chip System for Deciphering the Immunopathogenesis of Inflammatory Bowel Disease.

The multifactorial nature of inflammatory bowel disease (IBD) necessitates reliable and practical experimental models to elucidate its etiology and pathogenesis. To model the intestinal microenvironment at the onset of IBD in vitro, it is important to incorporate relevant cellular and noncellular components before inducing stepwise pathogenic developments. A novel intestine-on-chip system for investigating multiple aspects of IBD's immunopathogenesis is presented. The system includes an array of tight and polarized barrier models formed from intestinal epithelial cells on an in-vivo-like subepithelial matrix within one week. The dynamic remodeling of the subepithelial matrix by cells or their secretome demonstrates the physiological relevance of the on-chip barrier models. The system design enables introduction of various immune cell types and inflammatory stimuli at specific locations in the same barrier model, which facilitates investigations of the distinct roles of each cell type in intestinal inflammation development. It is showed that inflammatory behavior manifests in an upregulated expression of inflammatory markers and cytokines (TNF-α). The neutralizing effect of the anti-inflammatory antibody Infliximab on levels of TNF-α and its inducible cytokines could be explicitly shown. Overall, an innovative approach to systematically developing a microphysiological system to comprehend immune-system-mediated disorders of IBD and to identify new therapeutic strategies is presented.

Endoscopic Anterior Lumbar Interbody Fusion: Systematic Review and Meta-Analysis.

Laparoscopic anterior lumbar interbody fusion (L-ALIF), which employs laparoscopic cameras to facilitate a less invasive approach, originally gained traction during the 1990s but has subsequently fallen out of favor. As the envelope for endoscopic approaches continues to be pushed, a recurrence of interest in laparoscopic and/or endoscopic anterior approaches seems possible. Therefore, evaluating the current evidence base in regard to this approach is of much clinical relevance. To this end, a systematic literature search was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the following keywords: "(laparoscopic OR endoscopic) AND (anterior AND lumbar)." Out of the 441 articles retrieved, 22 were selected for quantitative analysis. The primary outcome of interest was the radiographic fusion rate. The secondary outcome was the incidence of perioperative complications. Meta-analysis was performed using RStudio's "metafor" package. Of the 1,079 included patients (mean age, 41.8±2.9 years), 481 were males (44.6%). The most common indication for L-ALIF surgery was degenerative disk disease (reported by 18 studies, 81.8%). The mean follow-up duration was 18.8±11.2 months (range, 6-43 months). The pooled fusion rate was 78.9% (95% confidence interval [CI], 68.9-90.4). Complications occurred in 19.2% (95% CI, 13.4-27.4) of L-ALIF cases. Additionally, 7.2% (95% CI, 4.6-11.4) of patients required conversion from L-ALIF to open surgery. Although L-ALIF does not appear to be supported by studies available in the literature, it is important to consider the context from which these results have been obtained. Even if these results are taken at face value, the failure of endoscopy to have a role in the ALIF approach does not mean that it should not be incorporated in posterior approaches.

Techniques for restoring optimal spinal biomechanics to alleviate symptoms in Bertolotti syndrome: illustrative case.

BACKGROUND: Lumbosacral transitional vertebrae (LSTVs) are congenital anomalies that occur in the spinal segments of L5-S1. These vertebrae result from sacralization of the lowermost lumbar segment or lumbarization of the uppermost sacral segment. When the lowest lumbar vertebra fuses or forms a false joint with the sacrum (pseudoarticulation), it can cause pain and manifest clinically as Bertolotti syndrome. OBSERVATIONS: A 36-year-old female presented with severe right-sided low-back pain. Computed tomography was unremarkable except for a right-sided Castellvi type IIA LSTV. The pain proved refractory to physical therapy and lumbar epidural spinal injections, but targeted steroid and bupivacaine injection of the pseudoarticulation led to 2 weeks of complete pain relief. She subsequently underwent minimally invasive resection of the pseudoarticulation, with immediate improvement in her low-back pain. The patient continued to be pain free at the 3-year follow-up. LESSONS: LSTVs alter the biomechanics of the lumbosacral spine, which can lead to medically refractory mechanical pain requiring surgical intervention. Select patients with Bertolotti syndrome can benefit from operative management, including resection, fusion, or decompression of the pathologic joint.

Patient-Reported Outcomes among Multiple Myeloma Patients Treated with Standard of Care Idecabtagene Vicleucel.

Idecabtagene vicleucel (ide-cel) was the first FDA-approved chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma (RRMM) patients. This was the first study to evaluate patient-reported outcomes (PROs) among RRMM patients receiving ide-cel in standard of care (SOC). We prospectively assessed health-related quality of life (HRQOL) and symptoms from pre-infusion (baseline) through day (D)90 post-infusion. Baseline PRO associations with patient characteristics, mean PRO changes, and time to stable change were evaluated with t-tests, linear mixed-effects models, and Kaplan-Meier analyses, respectively. Within-person change scores and minimally important difference thresholds determined clinical and meaningful significance. Participants (n = 42) were a median of 66 years old (range: 43-81). At baseline, extramedullary disease was associated with worse physical well-being (p = 0.008), global pain (p < 0.001), performance status (p = 0.002), and overall symptom burden (p < 0.001). Fatigue (p < 0.001) and functional well-being (p = 0.003) worsened by D7 before returning to baseline levels. Overall HRQOL (p = 0.008) and physical well-being (p < 0.001) improved by D60. Most participants reported PRO improvement (10-57%) or maintenance (23-69%) by D90. The median time it took to stabile deterioration in functional well-being was 14 days. The median time it took to stabile improvement in physical and emotional well-being was 60 days. Overall, RRMM patients reported improvements or maintenance of HRQOL and symptom burden after SOC ide-cel.

Assessing survival outcomes and complication profiles following surgical excision and radiotherapy as interventions for skull base chordoma: a systematic review of operative margins and surgical approaches.

INTRODUCTION: Despite their precarious behavioral classification (benign and low grade on histopathology yet behaviorally malignant), great strides have been taken to improve prognostication and treatment paradigms for patients with skull base chordoma. With respect to surgical techniques, lateral transcranial (TC) approaches have traditionally been used, however endoscopic endonasal approaches (EEA) have been advocated for midline lesions. Nonetheless, due to the rarity of this pathology (0.2% of all intracranial neoplasms), investigations within the literature remain limited to small retrospective series. Furthermore, radiotherapeutic treatments investigated to date have proven largely ineffective. METHODS: Accordingly, we performed a systematic review in order to profile surgical and survival outcomes for skull base chordoma. Fixed and random-effect meta-analyses were performed for categorical variables including GTR, STR, 5-year OS, 10-year OS, 5-year PFS, and 10-year PFS. Additionally, we pooled eligible studies for formal meta-analysis to compare outcomes by surgical approach (lateral versus midline). Statistical analyses were performed using R Studio 'metafor' package or Cochrane Review Manager. Furthermore, meta-analysis of pooled mortality rates and sub-analyses of operative margin and surgical complications were used to compare midline versus lateral approaches via the Mantel-Haenszel method. We considered all p-values < 0.05 to be statistically significant. RESULTS: Following the systematic search and screen, 55 studies published between 1993 and 2022 reporting data for 2453 patients remained eligible for analysis. Sex distribution was comparable between males and females, with a slight predominance of male-identifying patients (0.5625 [95% CI: 0.5418; 0.3909]). Average age at diagnosis was 42.4 ± 12.5 years, while average age of treatment initiation was 43.0 ± 10.6 years. Overall, I2 value indicated notable heterogeneity across the 55 studies [I2 = 56.3% (95%CI: 44.0%; 65.9%)]. With respect to operative margins, the rate of GTR was 0.3323 [95% CI: 0.2824; 0.3909], I2 = 91.9% [95% CI: 90.2%; 93.4%], while the rate of STR was significantly higher at 0.5167 [95% CI: 0.4596; 0.5808], I2 = 93.1% [95% CI: 91.6%; 94.4%]. The most common complication was CSF leak (5.4%). In terms of survival outcomes, 5-year OS rate was 0.7113 [95% CI: 0.6685; 0.7568], I2 = 91.9% [95% CI: 90.0%; 93.5%]. 10-year OS rate was 0.4957 [95% CI: 0.4230; 0.5809], I2 = 92.3% [95% CI: 89.2%; 94.4%], which was comparable to the 5-year PFS rate of 0.5054 [95% CI: 0.4394; 0.5813], I2 = 84.2% [95% CI: 77.6%; 88.8%] and 10-yr PFS rate of 0.4949 [95% CI: 0.4075; 0.6010], I2 = 14.9% [95% CI: 0.0%; 87.0%]. There were 55 reported deaths for a perioperative mortality rate of 2.5%. The relative risk for mortality in the midline group versus the lateral approach group did not indicate any substantial difference in survival according to laterality of approach (-0.93 [95% CI: -1.03, -0.97], I2 = 95%, (p < 0.001). CONCLUSION: Overall, these results indicate good 5-year survival outcomes for patients with skull base chordoma; however, 10-year prognosis for skull base chordoma remains poor due to its radiotherapeutic resistance and high recurrence rate. Furthermore, mortality rates among patients undergoing midline versus lateral skull base approaches appear to be equivocal.

The WW domain of IQGAP1 binds directly to the p110α catalytic subunit of PI 3-kinase.

IQGAP1 is a multi-domain cancer-associated protein that serves as a scaffold protein for multiple signaling pathways. Numerous binding partners have been found for the calponin homology, IQ and GAP-related domains in IQGAP1. Identification of a binding partner for its WW domain has proven elusive, however, even though a cell-penetrating peptide derived from this domain has marked anti-tumor activity. Here, using in vitro binding assays with human proteins and co-precipitation from human cells, we show that the WW domain of human IQGAP1 binds directly to the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K). In contrast, the WW domain does not bind to ERK1/2, MEK1/2, or the p85α regulatory subunit of PI3K when p85α is expressed alone. However, the WW domain is able to bind to the p110α/p85α heterodimer when both subunits are co-expressed, as well as to the mutationally activated p110α/p65α heterodimer. We present a model of the structure of the IQGAP1 WW domain, and experimentally identify key residues in the hydrophobic core and beta strands of the WW domain that are required for binding to p110α. These findings contribute to a more precise understanding of IQGAP1-mediated scaffolding, and of how IQGAP1-derived therapeutic peptides might inhibit tumorigenesis.

speedingCARs: accelerating the engineering of CAR T cells by signaling domain shuffling and single-cell sequencing.

Chimeric antigen receptors (CARs) consist of an antigen-binding region fused to intracellular signaling domains, enabling customized T cell responses against targets. Despite their major role in T cell activation, effector function and persistence, only a small set of immune signaling domains have been explored. Here we present speedingCARs, an integrated method for engineering CAR T cells via signaling domain shuffling and pooled functional screening. Leveraging the inherent modularity of natural signaling domains, we generate a library of 180 unique CAR variants genomically integrated into primary human T cells by CRISPR-Cas9. In vitro tumor cell co-culture, followed by single-cell RNA sequencing (scRNA-seq) and single-cell CAR sequencing (scCAR-seq), enables high-throughput screening for identifying several variants with tumor killing properties and T cell phenotypes markedly different from standard CARs. Mapping of the CAR scRNA-seq data onto that of tumor infiltrating lymphocytes further helps guide the selection of variants. These results thus help expand the CAR signaling domain combination space, and supports speedingCARs as a tool for the engineering of CARs for potential therapeutic development.

Urinary neutrophil gelatinase-associated lipocalin predicted to contrast-associated acute kidney injury after planned percutaneous coronary intervention in elderly patients.

AIM: To determine the proportion of contrast-associated acute kidney injury (CA-AKI) after percutaneous coronary intervention (PCI) and the predictive value of urine neutrophil gelatinase-associated lipocalin (uNGAL) for CA-AKI in elderly patients with chronic coronary artery disease. METHODS: A total of 509 patients who had planned percutaneous coronary intervention (mean age was 63.58 ± 11.63 years and 63.3% of males) were divided into two groups: group 1 (n = 153; elderly patients) with ≥70 years old and group 2 (n = 356) with <70 years old. Urine NGAL was measured by the ELISA method. Clinical and laboratory data were collected on the day before intervention. CA-AKI was defined based on Kidney Disease: Improving Global Outcomes criteria. RESULTS: The ratio of CA-AKI in group 1 was 23.5% which was higher than that of group 2 (8.7%) with a p-value < 0.001. Urine NGAL level in group 1 was significantly higher than that of group 2 [31.3 (19.16-55.13) ng/ml vs. 19.86 (13.21-29.04) ng/ml, p < 0.001]. At a cut-off value of 44.43 ng/ml, uNGAL had a predictive value for CA-AKI in all patients (AUC = 0.977, p < 0.001). Especially at a cut-off value of 44.14 ng/ml, uNGAL had a predictive value for CA-AKI in elderly patients (AUC = 0.979, p < 0.001). CONCLUSIONS: The rate of CA-AKI after PCI in elderly patients was 23.5%. Urine NGAL before PCI had a good predictive value for CA-AKI in elderly patients with chronic coronary artery disease.

Cardiac glycosides stimulate endocytosis of GLUT1 via intracellular Na+ ,K+ -ATPase α3-isoform in human cancer cells.

Glucose transporter GLUT1 plays a primary role in the glucose metabolism of cancer cells. Here, we found that cardiac glycosides (CGs) such as ouabain, oleandrin, and digoxin, which are Na+ ,K+ -ATPase inhibitors, decreased the GLUT1 expression in the plasma membrane of human cancer cells (liver cancer HepG2, colon cancer HT-29, gastric cancer MKN45, and oral cancer KB cells). The effective concentration of ouabain was lower than that for inhibiting the activity of Na+ ,K+ -ATPase α1-isoform (α1NaK) in the plasma membrane. The CGs also inhibited [3 H]2-deoxy- d-glucose uptake, lactate secretion, and proliferation of the cancer cells. In intracellular vesicles of human cancer cells, Na+ ,K+ -ATPase α3-isoform (α3NaK) is abnormally expressed. Here, a low concentration of ouabain inhibited the activity of α3NaK. Knockdown of α3NaK significantly inhibited the ouabain-decreased GLUT1 expression in HepG2 cells, while the α1NaK knockdown did not. Consistent with the results in human cancer cells, CGs had no effect on GLUT1 expression in rat liver cancer dRLh-84 cells where α3NaK was not endogenously expressed. Interestingly, CGs decreased GLUT expression in the dRLh-84 cells exogenously expressing α3NaK. In HepG2 cells, α3NaK was found to be colocalized with TPC1, a Ca2+ -releasing channel activated by nicotinic acid adenine dinucleotide phosphate (NAADP). The CGs-decreased GLUT1 expression was significantly inhibited by a Ca2+ chelator, a Ca2+ -ATPase inhibitor, and a NAADP antagonist. The GLUT1 decrease was also attenuated by inhibitors of dynamin and phosphatidylinositol-3 kinases (PI3Ks). In conclusion, the binding of CGs to intracellular α3NaK elicits the NAADP-mediated Ca2+ mobilization followed by the dynamin-dependent GLUT1 endocytosis in human cancer cells.

Fluorescence-Shadowing Nanoparticle Clusters for Real-Time Monitoring of Tumor Progression.

Monitoring tumor progression is important for elucidating appropriate therapeutic strategies in response to anticancer therapeutics. To fluorescently monitor the in vivo levels of tumor-specific enzymes, we prepared matrix metalloprotease (MMP)-responsive gold nanoparticle (AuNP) clusters to sense tumor microenvironments. Specifically, AuNPs and quantum dots (QDs) were surface-engineered with two poly(ethylene glycol) [PEG] shells and cyclooctyne moieties, respectively, for the copper-free click reaction. Upon "peeling off" of the secondary shell from the double-PEGylated AuNPs under MMP-rich conditions, shielded azide moieties of the AuNPs were displayed toward the QD, and those two particles were clicked into nanoparticle clusters. This consequently resulted in a dramatic size increase and fluorescence quenching of QDs via fluorescence energy transfer (FRET) due to the molecular proximity of the particles. We observed that FRET efficiency was modulated via changes in MMP levels and exposure time. Cancer cell numbers exhibited a strong correlation with FRET efficiency, and in vivo studies that employed solid tumor models accordingly showed that FRET efficiency was dependent on the tumor size. Thus, we envision that this platform can be tailored and optimized for tumor monitoring based on MMP levels in solid tumors.

An Immunocompetent Microphysiological System to Simultaneously Investigate Effects of Anti-Tumor Natural Killer Cells on Tumor and Cardiac Microtissues.

Existing first-line cancer therapies often fail to cope with the heterogeneity and complexity of cancers, so that new therapeutic approaches are urgently needed. Among novel alternative therapies, adoptive cell therapy (ACT) has emerged as a promising cancer treatment in recent years. The limited clinical applications of ACT, despite its advantages over standard-of-care therapies, can be attributed to (i) time-consuming and cost-intensive procedures to screen for potent anti-tumor immune cells and the corresponding targets, (ii) difficulties to translate in-vitro and animal-derived in-vivo efficacies to clinical efficacy in humans, and (iii) the lack of systemic methods for the safety assessment of ACT. Suitable experimental models and testing platforms have the potential to accelerate the development of ACT. Immunocompetent microphysiological systems (iMPS) are microfluidic platforms that enable complex interactions of advanced tissue models with different immune cell types, bridging the gap between in-vitro and in-vivo studies. Here, we present a proof-of-concept iMPS that supports a triple culture of three-dimensional (3D) colorectal tumor microtissues, 3D cardiac microtissues, and human-derived natural killer (NK) cells in the same microfluidic network. Different aspects of tumor-NK cell interactions were characterized using this iMPS including: (i) direct interaction and NK cell-mediated tumor killing, (ii) the development of an inflammatory milieu through enrichment of soluble pro-inflammatory chemokines and cytokines, and (iii) secondary effects on healthy cardiac microtissues. We found a specific NK cell-mediated tumor-killing activity and elevated levels of tumor- and NK cell-derived chemokines and cytokines, indicating crosstalk and development of an inflammatory milieu. While viability and morphological integrity of cardiac microtissues remained mostly unaffected, we were able to detect alterations in their beating behavior, which shows the potential of iMPS for both, efficacy and early safety testing of new candidate ACTs.

Atom transfer radical-polymerized cationic shells on gold nanoparticles for near infrared-triggered photodynamic therapy of tumor-bearing animals.

Gold nanoparticles (AuNPs) were surface-engineered with a cationic corona to enhance the incorporation of photosensitizers for photodynamic therapy (PDT). The cationic corona composed of poly(2-(dimethylamino)ethyl methacrylate) was atom transfer radical-polymerized on the surface of the AuNPs. The cationic corona of the engineered surface was characterized by dynamic light scattering, electron microscopy, Raman spectroscopy, and mass spectroscopy. Chlorin-e6 (Ce6) incorporated onto the surface-engineered AuNPs exhibited higher cell incorporation efficiency than bare AuNPs. Ce6-incorporated AuNPs were confirmed to release singlet oxygen upon NIR irradiation. Compared to Ce6, Ce6-incorporated AuNPs exhibited higher cellular uptake and cytotoxicity against cancer cells in an irradiation time-dependent manner. Near-infrared-irradiated animals administered Ce6-incorporated AuNPs exhibited higher levels of tumor suppression without noticeable body weight loss. This result was attributed to the higher localization of Ce6 at the tumor sites to induce cancer cell apoptosis. Thus, we envision that engineered AuNPs with cationic corona can be tailored to effectively deliver photosensitizers to tumor sites for photodynamic therapy.

Self-assembled cell sheets composed of mesenchymal stem cells and gelatin nanofibers for the treatment of full-thickness wounds.

Cell sheet engineering has attracted great attention because thin layers of tissue can be easily transplanted to defect sites. Wound-dressing materials are required to support fast re-epithelization, both with keratinocytes and fibroblasts, to enhance the prognosis and therapeutic outcomes. We prepared self-assembled cell sheets composed of adipocyte-derived stem cells (ADSCs) and surface-engineered nanofibrils (NFs). NFs were surface-engineered with multilayers of gelatin so that the cell sheets could spontaneously assemble within 3 days in cell culture plates. Dorsal wounds transplanted with the cell sheets exhibited higher wound-healing rates when a high concentration of gelatin was immobilized on the surfaces of the NFs. Histochemical staining revealed that those with gelatin-immobilized NFs showed a higher expression of cytokeratin and collagen in the re-epithelized epidermis. Keratinocytic differentiation of the epidermis was molecularly evidenced by the higher expression of keratinocyte-specific genes.

The Clinical Course after Long-Term Acute Care Hospital Admission among Older Medicare Beneficiaries.

OBJECTIVES: Long-term acute care (LTAC) hospitals provide extended complex post-acute care to more than 120 000 Medicare beneficiaries annually, with the goal of helping patients to regain independence and recover. Because little is known about patients' long-term outcomes, we sought to examine the clinical course after LTAC admission. DESIGN: Nationally representative 5-year cohort study using 5% Medicare data from 2009 to 2013. SETTING: LTAC hospitals. PARTICIPANTS: Hospitalized Medicare fee-for-service beneficiaries 65 years of age or older who were transferred to an LTAC hospital. MEASUREMENTS: Mortality, recovery (defined as achieving 60 consecutive days alive without inpatient care), time spent in an inpatient facility following LTAC hospital admission, receipt of an artificial life-prolonging procedure (feeding tube, tracheostomy, hemodialysis), and palliative care physician consultation. RESULTS: Of 14 072 hospitalized older adults transferred to an LTAC hospital, median survival was 8.3 months, and 1- and 5-year survival rates were 45% and 18%, respectively. Following LTAC admission, 53% never achieved a 60-day recovery. The median time of their remaining life a patient spent as an inpatient after LTAC admission was 65.6% (interquartile range = 21.4%-100%). More than one-third (36.9%) died in an inpatient setting, never returning home after the LTAC admission. During the preceding hospitalization and index LTAC admission, 30.9% received an artificial life-prolonging procedure, and 1% had a palliative care physician consultation. CONCLUSION: Hospitalized older adults transferred to LTAC hospitals have poor survival, spend most of their remaining life as an inpatient, and frequently undergo life-prolonging procedures. This prognostic understanding is essential to inform goals of care discussions and prioritize healthcare needs for hospitalized older adults admitted to LTAC hospitals. Given the exceedingly low rates of palliative care consultations, future research is needed to examine unmet palliative care needs in this population. J Am Geriatr Soc 67:2282-2288, 2019.

Predicting all-cause readmissions using electronic health record data from the entire hospitalization: Model development and comparison.

BACKGROUND: Incorporating clinical information from the full hospital course may improve prediction of 30-day readmissions. OBJECTIVE: To develop an all-cause readmissions risk-prediction model incorporating electronic health record (EHR) data from the full hospital stay, and to compare "full-stay" model performance to a "first day" and 2 other validated models, LACE (includes Length of stay, Acute [nonelective] admission status, Charlson Comorbidity Index, and Emergency department visits in the past year), and HOSPITAL (includes Hemoglobin at discharge, discharge from Oncology service, Sodium level at discharge, Procedure during index hospitalization, Index hospitalization Type [nonelective], number of Admissions in the past year, and Length of stay). DESIGN: Observational cohort study. SUBJECTS: All medicine discharges between November 2009 and October 2010 from 6 hospitals in North Texas, including safety net, teaching, and nonteaching sites. MEASURES: Thirty-day nonelective readmissions were ascertained from 75 regional hospitals. RESULTS: Among 32,922 admissions (validation = 16,430), 12.7% were readmitted. In addition to many first-day factors, we identified hospital-acquired Clostridium difficile infection (adjusted odds ratio [AOR]: 2.03, 95% confidence interval [CI]: 1.18-3.48), vital sign instability on discharge (AOR: 1.25, 95% CI: 1.15-1.36), hyponatremia on discharge (AOR: 1.34, 95% CI: 1.18-1.51), and length of stay (AOR: 1.06, 95% CI: 1.04-1.07) as significant predictors. The full-stay model had better discrimination than other models though the improvement was modest (C statistic 0.69 vs 0.64-0.67). It was also modestly better in identifying patients at highest risk for readmission (likelihood ratio +2.4 vs. 1.8-2.1) and in reclassifying individuals (net reclassification index 0.02-0.06). CONCLUSIONS: Incorporating clinically granular EHR data from the full hospital stay modestly improves prediction of 30-day readmissions. Given limited improvement in prediction despite incorporation of data on hospital complications, clinical instabilities, and trajectory, our findings suggest that many factors influencing readmissions remain unaccounted for. Further improvements in readmission models will likely require accounting for psychosocial and behavioral factors not currently captured by EHRs. Journal of Hospital Medicine 2016;11:473-480. © 2016 Society of Hospital Medicine.

National Use of Safety-Net Clinics for Primary Care among Adults with Non-Medicaid Insurance in the United States.

OBJECTIVE: To describe the prevalence, characteristics, and predictors of safety-net use for primary care among non-Medicaid insured adults (i.e., those with private insurance or Medicare). METHODS: Cross-sectional analysis using the 2006-2010 National Ambulatory Medical Care Surveys, annual probability samples of outpatient visits in the U.S. We estimated national prevalence of safety-net visits using weighted percentages to account for the complex survey design. We conducted bivariate and multivariate logistic regression analyses to examine characteristics associated with safety-net clinic use. RESULTS: More than one-third (35.0%) of all primary care safety-net clinic visits were among adults with non-Medicaid primary insurance, representing 6,642,000 annual visits nationally. The strongest predictors of safety-net use among non-Medicaid insured adults were: being from a high-poverty neighborhood (AOR 9.53, 95% CI 4.65-19.53), being dually eligible for Medicare and Medicaid (AOR 2.13, 95% CI 1.38-3.30), and being black (AOR 1.97, 95% CI 1.06-3.66) or Hispanic (AOR 2.28, 95% CI 1.32-3.93). Compared to non-safety-net users, non-Medicaid insured adults who used safety-net clinics had a higher prevalence of diabetes (23.5% vs. 15.0%, p<0.001), hypertension (49.4% vs. 36.0%, p<0.001), multimorbidity (≥2 chronic conditions; 53.5% vs. 40.9%, p<0.001) and polypharmacy (≥4 medications; 48.8% vs. 34.0%, p<0.001). Nearly one-third (28.9%) of Medicare beneficiaries in the safety-net were dual eligibles, compared to only 6.8% of Medicare beneficiaries in non-safety-net clinics (p<0.001). CONCLUSIONS: Safety net clinics are important primary care delivery sites for non-Medicaid insured minority and low-income populations with a high burden of chronic illness. The critical role of safety-net clinics in care delivery is likely to persist despite expanded insurance coverage under the Affordable Care Act.