An AI-driven clinical care pathway to reduce 30-day readmission for chronic obstructive pulmonary disease (COPD) patients.

Healthcare regulatory agencies have mandated a reduction in 30-day hospital readmission rates and have targeted COPD as a major contributor to 30-day readmissions. We aimed to develop and validate a simple tool deploying an artificial neural network (ANN) for early identification of COPD patients with high readmission risk. Using COPD patient data from eight hospitals within a large urban hospital system, four variables were identified, weighted and validated. These included the number of in-patient admissions in the previous 6 months, the number of medications administered on the first day, insurance status, and the Rothman Index on hospital day one. An ANN model was trained to provide a predictive algorithm and validated on an additional dataset from a separate time period. The model was implemented in a smartphone app (Re-Admit) incorporating four input risk factors, and a clinical care plan focused on high-risk readmission candidates was then implemented. Subsequent readmission data was analyzed to assess impact. The areas under the curve of receiver operating characteristics predicting readmission with ANN is 0.77, with sensitivity 0.75 and specificity 0.67 on the separate validation data. Readmission rates in the COPD high-risk subgroup after app and clinical intervention implementation saw a significant 48% decline. Our studies show the efficacy of ANN model on predicting readmission risks for COPD patients. The AI enabled Re-Admit smartphone app predicts readmission risk on day one of the patient's admission, allowing for early implementation of medical, hospital, and community resources to optimize and improve clinical care pathways.

Sleep-Disordered Breathing and Idiopathic Normal-Pressure Hydrocephalus: Recent Pathophysiological Advances.

PURPOSE OF REVIEW: Idiopathic normal-pressure hydrocephalus (iNPH) is characterized clinically by ventriculomegaly, abnormal gait, falls, incontinence, and cognitive decline. This article reviews recent advances in the pathophysiology of iNPH concerning sleep-disordered breathing (SDB) and glymphatic circulation during deep sleep. RECENT FINDINGS: The authors found iNPH frequently associated with obstructive sleep apnea (OSA). A critical factor in iNPH is intracranial venous hypertension delaying drainage of cerebrospinal fluid (CSF) into the cerebral venous sinuses. CSF-venous blood circulates in the jugular veins and finally drains into the heart. During SDB, repeated reflex attempts to breathe induce strong respiratory efforts against a closed glottis thereby increasing the negative intrathoracic pressure. This causes atrial distortion and decreases venous return to the heart resulting in retrograde intracranial venous hypertension. Additionally, repeated awakenings from OSA impede sleep-associated circulation of interstitial CSF into the glymphatic circulation contributing to hydrocephalus. Sleep has become a critical element in the cognitive changes of aging including iNPH.

Hippocampal Sclerosis in Older Patients: Practical Examples and Guidance With a Focus on Cerebral Age-Related TDP-43 With Sclerosis.

CONTEXT: - Autopsy studies of the older population (≥65 years of age), and particularly of the "oldest-old" (≥85 years of age), have identified a significant proportion (∼20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. OBJECTIVE: - To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). DATA SOURCES: - Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. CONCLUSIONS: - In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology.

Post-traumatic amaurosis secondary to paraophthalmic internal carotid artery pseudoaneurysm treated with pipeline embolization device.

During evaluation for monocular visual loss, a 48-year-old woman was found to have a posttraumatic paraophthalmic internal carotid artery (ICA) pseudoaneurysm. She underwent reconstruction of the ophthalmic segment of the right ICA with a Pipeline embolization device but her vision did not return.

Risk factors for delayed hematuria following photoselective vaporization of the prostate.

PURPOSE: Photoselective vaporization of the prostate has become an increasingly popular option for the treatment of benign prostatic hyperplasia. However, delayed bleeding has been raised as a potential issue as more cases are performed. We characterize delayed bleeding after photoselective vaporization of the prostate and identify associated risk factors. MATERIALS AND METHODS: We defined delayed gross hematuria as any complaint of hematuria following hospital discharge, and further stratified it as delayed gross hematuria requiring emergency department evaluation, hospital admission, continuous bladder irrigation, transfusions or reoperation. We performed an explicit chart review of 290 patients who underwent photoselective vaporization of the prostate at a single center from 2002 through 2009. Exposures of interest included age, prostate volume, followup duration, operative factors (watts/joules), and use of oral anticoagulation therapy or 5α-reductase inhibitors. RESULTS: Delayed gross hematuria occurred in 33.8% of patients during an average followup of 33 months. For 8.5% of patients the bleeding was severe enough to prompt presentation to the emergency department. For 4.8% of patients hospitalization was required and for 4.5% reoperation was required. Multivariate analysis revealed that the odds of bleeding increased with prostate size (OR 1.08, 1.03-1.14), longer followup (OR 1.35, 1.12-1.62) and anticoagulant use (OR 3.35, 1.43-7.83), and decreased with increasing age (OR 0.71, 0.51-0.98) and use of a 5α-reductase inhibitor (OR 0.41, 0.24-0.73). CONCLUSIONS: Delayed hematuria occurs commonly after photoselective vaporization of the prostate but severe hematuria is rare. Larger prostate size, longer followup and use of anticoagulation were associated with a higher risk of delayed gross hematuria while preoperative 5α-reductase inhibitor use and older age were protective.

Effects of semen storage and separation techniques on sperm DNA fragmentation.

OBJECTIVE: To determine the effect of semen storage and separation techniques on sperm DNA fragmentation. DESIGN: Controlled clinical study. SETTING: An assisted reproductive technology laboratory. PATIENT(S): Thirty normoozospermic semen samples obtained from patients undergoing infertility evaluation. INTERVENTION(S): One aliquot from each sample was immediately prepared (control) for the sperm chromatin dispersion assay (SCD). Aliquots used to assess storage techniques were treated in the following ways: snap frozen by liquid nitrogen immersion, slow frozen with Tris-yolk buffer and glycerol, kept on ice for 24 hours or maintained at room temperature for 4 and 24 hours. Aliquots used to assess separation techniques were processed by the following methods: washed and centrifuged in media, swim-up from washed sperm pellet, density gradient separation, density gradient followed by swim-up. DNA integrity was then measured by SCD. MAIN OUTCOME MEASURE(S): DNA fragmentation as measured by SCD. RESULT(S): There was no significant difference in fragmentation among the snap frozen, slow frozen, and wet-ice groups. Compared to other storage methods short-term storage at room temperature did not impact DNA fragmentation yet 24 hours storage significantly increased fragmentation. Swim-up, density gradient and density gradient/swim-up had significantly reduced DNA fragmentation levels compared with washed semen. Postincubation, density gradient/swim-up showed the lowest fragmentation levels. CONCLUSION(S): The effect of sperm processing methods on DNA fragmentation should be considered when selecting storage or separation techniques for clinical use.

Modulation of cellular invasion by VEGF-C expression in squamous cell carcinoma of the head and neck.

OBJECTIVE: To determine how vascular endothelial growth factor C (VEGF-C) affects tumor cell invasion and motility in squamous cell carcinoma of the head and neck (SCCHN). DESIGN: A molecular biology study. The VEGF-C coding sequence was cloned into an expression vector and stably transfected into the SCCHN cell line SCC116 to create the SCC116-VEGFC line. RNA interference (RNAi) was used to block VEGF-C expression. An adenoviral system for expressing VEGF-C RNAi was developed and tested. SETTING: An academic hospital laboratory. MAIN OUTCOME MEASURES: Relative VEGF-C RNA levels were determined by real-time quantitative reverse transcriptase-polymerase chain reaction, and protein expression was evaluated by Western blot. Cellular invasion was evaluated by 24-hour semipermeable membrane transit assay. RESULTS: SCC116-VEGFC cells had markedly increased expression of VEGF-C protein and RNA compared with normal SCC116 controls. SCC116-VEGFC cells produced marked increases in cellular invasion and motility compared with SCC116 cells. Blockade of VEGF-C expression by transfection of a VEGF-C RNAi expression plasmid into both SCC116 and SCC116-VEGFC cells induced a 38% decrease in SCCHN invasion and motility as tested by a semipermeable membrane invasion assay. We developed an adenoviral expression system for VEGF-C RNAi, which also induced a dose-dependent decrease in cellular invasion in the highly invasive DM12 cell line. CONCLUSIONS: These studies demonstrate that intracellular VEGF-C levels modulate in vitro SCCHN motility and invasion. Further work is needed to clarify the specific receptors and signaling pathways that are involved in SCCHN motility. Molecular therapies that inhibit the VEGF-C pathway may have clinical potential in the treatment of lymphatic metastasis in SCCHN.

Differential activity of sulindac metabolites against squamous cell carcinoma of the head and neck is mediated by p21waf1/cip1 induction and cell cycle inhibition.

Sulindac sulfide and sulindac sulfone have demonstrated anti-neoplastic and chemo-preventive activity against various human tumors, but few studies have examined the relative effectiveness of these drugs against squamous cell carcinoma of the head and neck (SCCHN). These compounds are metabolites of the nonsteroidal anti-inflammatory drug sulindac and differ in their ability to inhibit cyclooxygenase-2 (COX-2) enzyme function. Sulindac sulfide (the sulindac metabolite with COX-2 inhibitory function) demonstrated strong cell growth inhibition as measured by MTT and growth assays in UM-SCC-1 and SCC-25 cells, while sulindac sulfone had only moderate effect. Growth inhibition by sulindac sulfide was associated with a significant increase in percent G cells and activation of caspase-3. Sulindac sulfide induced expression of p21wafl/cipl in a dose-dependent fashion, decreased cyclin D1 protein levels, and increased Rb hypophosphorylation. p21waf1/cip1 protein levels increased without a significant increase in wild-type p53, suggesting that sulindac sulfide induces a p53-independent pathway regulating p2lwafl/ciP1 protein levels in SCCHN. Sulindac sulfide also induced dose-dependent expression of PPAR-gamma. In contrast, sulindac sulfone did not significantly alter apoptosis, cell cycle distribution or G1 checkpoint protein expression at doses below 200 microM. These results demonstrate the differential activity of sulindac metabolites and support the hypothesis that sulindac sulfide induced perturbations in SCCHN cellular proliferation could be regulated both by p21waf1/cip1-dependent cytostatic and caspase-dependent cytotoxic pathways.

Screening for esophageal luminal narrowing--a magnetic disc tablet as a bolus challenge: preliminary report.

Narrowing of the esophageal lumen often exists for months before being noted by the patient. Screening tests for such lesions would be useful, if applicable to office use. A magnetic disc tablet (14 mm in diameter and 5 mm thick) was fashioned by hand using dental acrylic material to enclose the magnet with a smooth watertight sheath. A magnetic detector was held on the anterior abdominal wall 2.5 cm below the xiphoid cartilage and 2.5 cm to its left. A significant change in reading indicated that the tablet had reached the cardia of the stomach. The magnetic tablet was readily detected in 11 patients without organic narrowing. Our method attempts to detect narrowing of the esophageal lumen by use of a magnetic disc tablet. Perhaps this will be of clinical usefulness in detecting esophageal disease before symptoms become apparent.