Cloud-Integrated Smart Nanomembrane Wearables for Remote Wireless Continuous Health Monitoring of Postpartum Women.

Noncommunicable diseases (NCD), such as obesity, diabetes, and cardiovascular disease, are defining healthcare challenges of the 21st century. Medical infrastructure, which for decades sought to reduce the incidence and severity of communicable diseases, has proven insufficient in meeting the intensive, long-term monitoring needs of many NCD disease patient groups. In addition, existing portable devices with rigid electronics are still limited in clinical use due to unreliable data, limited functionality, and lack of continuous measurement ability. Here, a wearable system for at-home cardiovascular monitoring of postpartum women-a group with urgently unmet NCD needs in the United States-using a cloud-integrated soft sternal device with conformal nanomembrane sensors is introduced. A supporting mobile application provides device data to a custom cloud architecture for real-time waveform analytics, including medical device-grade blood pressure prediction via deep learning, and shares the results with both patient and clinician to complete a robust and highly scalable remote monitoring ecosystem. Validated in a month-long clinical study with 20 postpartum Black women, the system demonstrates its ability to remotely monitor existing disease progression, stratify patient risk, and augment clinical decision-making by informing interventions for groups whose healthcare needs otherwise remain unmet in standard clinical practice.

Soft Wireless Bioelectronics Designed for Real-Time, Continuous Health Monitoring of Farmworkers.

Hotter summers caused by global warming and increased workload and duration are endangering the health of farmworkers, a high-risk population for heat-related illness (HRI), and deaths. Although prior studies using wearable sensors show the feasibility of employing field-collected data for HRI monitoring, existing devices still have limitations, such as data loss from motion artifacts, device discomfort from rigid electronics, difficulties with administering ingestible sensors, and low temporal resolution. Here, this paper introduces a wireless, wearable bioelectronic system with functionalities for continuous monitoring of skin temperature, electrocardiograms (ECG), heart rates (HR), and activities, configured in a single integrated package. Advanced nanomanufacturing based on laser machining allows rapid device fabrication and direct incorporation of sensors with a highly breathable substrate, allowing for managing excessive sweating and multimodal stresses. To validate the device's performance in agricultural settings, the device is applied to multiple farmworkers at various operations, including fernery, nursery, and crop. The accurate data recording, including high-fidelity ECG (signal-to-noise ratio: >20 dB), accurate HR (r = 0.89, r2 = 0.65 in linear correlation), and reliable temperature/activity, confirms the device's capability for multiparameter health monitoring of farmworkers.

Regulation of decellularized tissue remodeling via scaffold-mediated lentiviral delivery in anatomically-shaped osteochondral constructs.

Cartilage-derived matrix (CDM) has emerged as a promising scaffold material for tissue engineering of cartilage and bone due to its native chondroinductive capacity and its ability to support endochondral ossification. Because it consists of native tissue, CDM can undergo cellular remodeling, which can promote integration with host tissue and enables it to be degraded and replaced by neotissue over time. However, enzymatic degradation of decellularized tissues can occur unpredictably and may not allow sufficient time for mechanically competent tissue to form, especially in the harsh inflammatory environment of a diseased joint. The goal of the current study was to engineer cartilage and bone constructs with the ability to inhibit aberrant inflammatory processes caused by the cytokine interleukin-1 (IL-1), through scaffold-mediated delivery of lentiviral particles containing a doxycycline-inducible IL-1 receptor antagonist (IL-1Ra) transgene on anatomically-shaped CDM constructs. Additionally, scaffold-mediated lentiviral gene delivery was used to facilitate spatial organization of simultaneous chondrogenic and osteogenic differentiation via site-specific transduction of a single mesenchymal stem cell (MSC) population to overexpress either chondrogenic, transforming growth factor-beta 3 (TGF-ß3), or osteogenic, bone morphogenetic protein-2 (BMP-2), transgenes. Controlled induction of IL-1Ra expression protected CDM hemispheres from inflammation-mediated degradation, and supported robust bone and cartilage tissue formation even in the presence of IL-1. In the absence of inflammatory stimuli, controlled cellular remodeling was exploited as a mechanism for fusing concentric CDM hemispheres overexpressing BMP-2 and TGF-ß3 into a single bi-layered osteochondral construct. Our findings demonstrate that site-specific delivery of inducible and tunable transgenes confers spatial and temporal control over both CDM scaffold remodeling and neotissue composition. Furthermore, these constructs provide a microphysiological in vitro joint organoid model with site-specific, tunable, and inducible protein delivery systems for examining the spatiotemporal response to pro-anabolic and/or inflammatory signaling across the osteochondral interface.

Risk of Acute Ischemic Stroke in Patients With Monocular Vision Loss of Vascular Etiology.

BACKGROUND: To evaluate the risk of concurrent acute ischemic stroke and monocular vision loss (MVL) of vascular etiology. DESIGN: Retrospective, cross-sectional study. SUBJECTS: Patients aged 18 or older diagnosed with MVL of suspected or confirmed vascular etiology who had no other neurologic deficits and who received brain MRI within 7 days of onset of visual symptoms were included. METHODS: A medical record review was performed from 2013 to 2016 at Yale New Haven Hospital. Patients were included if vision loss was unilateral and due to transient monocular vision loss (TMVL), central retinal artery occlusion (CRAO), or branch retinal artery occlusion (BRAO). Any patients with neurologic deficits other than vision loss were excluded. Other exclusion criteria were positive visual phenomena, nonvascular intraocular pathology, and intracranial pathology other than ischemic stroke. MAIN OUTCOME MEASURES: The presence or absence of acute stroke on diffusion-weighted imaging (DWI) on brain MRI. RESULTS: A total of 641 records were reviewed, with 293 patients found to have MVL. After excluding those with focal neurologic deficits, there were 41 patients who met the inclusion criteria and received a brain MRI. Eight of the 41 subjects (19.5%) were found to have findings on brain MRI positive for acute cortical strokes. The proportion of lesion positive MRI was 1/23 (4.3%) in TMVL subjects, 4/12 (33.3%) in CRAO subjects, and 2/5 (40%) in BRAO subjects. Brain computed tomography (CT) scans were not able to identify the majority of acute stroke lesions in this study. CONCLUSIONS: Patients with MVL of vascular etiology such as TMVL, CRAO, or BRAO may have up to 19.5% risk of concurrent ischemic stroke, even when there are no other neurologic deficits. These strokes were detected acutely with brain MRI using DWI but were missed on CT.

UV-independent p53 mutations in sebaceous carcinoma of the eyelid.

PURPOSE: Sebaceous carcinoma of the eyelid is a potentially fatal malignancy that has been associated with p53 gene mutations. The purpose of this study is to determine the frequency of p53 mutations in sebaceous carcinoma of the eyelid and to determine whether there is any relationship between the presence of p53 mutations and tumor invasiveness. METHODS: Retrospective case series. Fourteen samples of sebaceous carcinoma that had been resected from Caucasian patients between 1994 and 2010 were analyzed for p53 gene mutations with PCR and Sequencher software. Patient charts were reviewed to draw clinicopathologic correlations in relation with the presence of p53 gene mutations. RESULTS: Seven of 14 (50%) sebaceous carcinoma samples were found to have p53 gene mutations. None of the samples had tandem mutations, which are caused by UV exposure. No statistically significant trend was found between the presence of p53 mutations and metastasis, recurrence, tumor size, TNM stage, and pagetoid spread. There was a similar frequency of p53 gene mutations found in stage T1, T2, and T3 tumors. CONCLUSIONS: p53 Mutations are found in a high percentage of sebaceous carcinomas in the Caucasian population. The absence of tandem mutations is consistent with the belief that sebaceous carcinoma develops as a UV-independent process. There does not appear to be a significant correlation between the presence of p53 mutations and tumor size, recurrence, metastasis, pagetoid spread, or location. The similar frequency of p53 mutations in both low- and high-stage tumors implies that p53 gene mutations may be involved in early stages of carcinogenesis of sebaceous carcinoma.

Clinicopathologic correlation of textural interface opacities in descemet stripping automated endothelial keratoplasty: a case study.

PURPOSE: The aim of this study was to describe the clinicopathologic correlation of textural interface opacities (TIOs) in a Descemet stripping automated endothelial keratoplasty (DSAEK) donor button after its removal. METHODS: A 75-year-old woman underwent combined phacoemulsification with intraocular lens placement and DSAEK in her right eye. She had TIOs 1 week postoperatively and continued to have poor visual acuity 8 months postoperatively. The original DSAEK graft was removed, and a repeat DSAEK procedure with a new donor disc was performed. A control corneal button was obtained from a 79-year-old woman who suffered chronic rejection and had a failed DSAEK. Both corneal specimens were sent for light and electron microscopy. RESULTS: Light microscopy of the donor tissue from the patient with TIOs showed stromal irregularities projecting from the cut anterior surface and the expected decrease in the endothelial cell density associated with the procedure and with artifacts. Electron microscopy examination showed irregular collagen fibrils of varying lengths at the stromal surface. Light and electron microscopy examination of the donor tissue from the control patient showed a smooth anterior stromal surface without projecting collagen fibrils. CONCLUSIONS: The histopathology of the endothelial disc from the patient with TIOs demonstrated variably irregular lamellae that extended from the anterior donor corneal stromal surface. These extending lamellae were absent on the anterior stromal surface of the control corneal disc, suggesting that they are one possible cause of TIOs and the subsequent suboptimal best-corrected visual acuity and quality of vision experienced by a subset of DSAEK-operated patients.

Histopathology of streptococcus mitis/oralis endophthalmitis after intravitreal injection with bevacizumab: a report of 7 patients.

PURPOSE: To report the histopathologic findings of a series of patients from an outbreak of Streptococcal endophthalmitis after intravitreal injection of bevacizumab prepared by a single compounding pharmacy. DESIGN: Case series. PARTICIPANTS: Seven surgical specimens (5 enucleated globes and 2 evisceration specimens) from 7 patients with endophthalmitis after intravitreal injection of bevacizumab. METHODS: Retrospective case series, including clinical data and histopathologic specimens examined by light microscopy. MAIN OUTCOME MEASURES: Review of clinical data included baseline visual acuity, clinical intervention, and time elapsed from injection to loss of globe. Histopathologic specimens were reviewed for pathologic changes at all tissue levels. RESULTS: Seven of 12 total patients (4 women, 3 men; mean age, 77.7 years) from an outbreak of Streptococcus mitis/oralis endophthalmitis after bevacizumab injection ultimately sustained loss of the affected globe, with an average of 139.1 days elapsed between injection and globe loss. Mean time from injection to presentation was 2.86 days (range, 1-6), and all patients were initially treated with vitreous tap and injection. Although histologic review of surgical specimens disclosed a wide range of pathologic tissue changes, recurring patterns of tissue damage were evident. All 5 enucleated globes displayed retinal detachment, fibrous proliferation with cyclitic membrane formation, rubeosis iridis, and secondary angle closure. All 7 specimens displayed persistent choroidal inflammation, in 1 case 208 days after injection. Six of 7 specimens had foci of retinal necrosis. Although vitreous cultures were positive in all cases, no organisms were identified by light microscopy in any of the 7 specimens. CONCLUSIONS: S. mitis/oralis endophthalmitis is a devastating complication of intravitreal injection with bevacizumab with a high rate of globe loss (7 of 12 patients, 58.3%) and a wide variety of severe pathologic tissue changes. Although no organisms were identified in the examined tissues, persistent inflammation was present in all cases, and fibrous proliferation resulted in cyclitic membrane formation and retinal detachment in all enucleated globes. These findings suggest that potential globe-salvaging interventions must address a pattern of changes involving persistent, chronic inflammation and fibrovascular proliferation as key components.

Conjunctival keratoacanthoma.

An 83-year-old man presented with a 1-month history of a rapidly enlarging conjunctival mass. On examination, slit lamp biomicroscopy revealed a leukoplakic tumour at the temporal limbus. The lesion was excised with cryotherapy application to the limbus and conjunctival margins. Histopathology revealed a keratoacanthoma (KA). KA typically occurs on sun-exposed areas of the skin. Conjunctival KA is very rare, and differentiation between conventional squamous cell carcinoma (SCCA) and KA can be challenging. The present case highlights the indication for excisional surgery in patients with conjunctival KA using the no touch technique, cryotherapy, amniotic membrane and the histopathological differentiation between KA and SCCA.

Diagnosis of ocular surface lesions using ultra-high-resolution optical coherence tomography.

PURPOSE: To assess the use of ultra-high-resolution (UHR) optical coherence tomography (OCT) in the diagnosis of ocular surface lesions. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Fifty-four eyes of 53 consecutive patients with biopsy-proven ocular surface lesions: 8 primary acquired melanosis lesions, 5 amelanotic melanoma lesions, 2 nevi, 19 ocular surface squamous neoplasia lesions, 1 histiocytosis lesion, 6 conjunctival lymphoma lesions, 2 conjunctival amyloidosis lesions, and 11 pterygia lesions. INTERVENTION: Ultra-high-resolution OCT imaging of the ocular surface lesions. MAIN OUTCOME MEASURES: Clinical course and photographs, UHR OCT image, and histopathologic findings. RESULTS: Ultra-high-resolution OCT images of all examined ocular surface lesions showed close correlation with the obtained histopathologic specimens. When clinical differential diagnosis of ocular surface lesions was broad, UHR OCT images provided optical signs indicating a more specific diagnosis and management. In cases of amelanotic melanoma, conjunctival amyloidosis, and primary histiocytosis and in 1 case of ocular surface squamous neoplasia, UHR OCT was instrumental in guiding the diagnosis. In those cases, UHR OCT suggested that the presumed clinical diagnosis was incorrect and favored a diagnosis that later was confirmed by histopathologic examination. CONCLUSIONS: Correlations between UHR OCT and histopathologic findings confirm that UHR OCT is an adjunctive diagnostic method that can provide a noninvasive means to help guide diagnosis and management of ocular surface lesions. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Molecular histopathology using gold nanorods and optical coherence tomography.

PURPOSE: To examine the novel application of a commercially available optical coherence tomography (OCT) system toward molecular histopathology using gold nanorod (GNR) linked antibodies as a functionalized contrast agent to evaluate ocular surface squamous neoplasia (OSSN). METHODS: GNRs were synthesized and covalently attached to anti-glucose transporter-1 (GLUT-1) antibodies via carbodiimide chemistry. Three specimens from each of three distinct categories of human conjunctival tissue were selected for analysis, including conjunctiva without epithelial atypia (controls); conjunctival intraepithelial neoplasia, carcinoma in situ (CIS); and conjunctival squamous cell carcinoma (SCC). Tissue sections were incubated initially with GNR tagged anti-GLUT-1 antibodies and then with a fluorescent-tagged secondary antibody. Immunofluorescence and OCT imaging of the tissue was performed and the results were correlated to the light microscopic findings on traditional hemotoxyin and eosin stained sections. RESULTS: No binding of the functionalized GNRs was observed within the epithelium of three normal conjunctiva controls. While immunofluorescence disclosed variable binding of the functionalized GNRs to atypical epithelial cells in all six cases of OSSN, the enhancement of the OCT signal in three cases of CIS was insufficient to distinguish these specimens from normal controls. In two of three cases of SCC, binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to atypical epithelial cells which stained intensely on immunofluorescence imaging. Binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to regions of erythrocytes and hemorrhage which stained intensely on immunofluorescence imaging within all nine tested samples. CONCLUSIONS: We have demonstrated the use of OCT for molecular histopathology using functionalized gold nanorods in the setting of OSSN. Our results suggest a threshold concentration of functionalized GNRs within tissue is required to achieve a detectable enhancement in scattering of the OCT signal.

Prevalence, treatment, and outcomes of coexistent ocular surface squamous neoplasia and pterygium.

PURPOSE: The purpose of this study was to determine the prevalence of ocular surface squamous neoplasia (OSSN) coexisting with pterygia in South Florida and to study the treatment and related outcomes. DESIGN: Noninterventional retrospective study. PARTICIPANTS: A total of 2005 patients with surgically excised pterygia at the Bascom Palmer Eye Institute from 2000 to 2010. METHODS: Pathology reports of patients with pterygia were reviewed for evidence of OSSN. Patients were divided into the following groups: pterygium and no OSSN (group 1), clinically suspected OSSN with pterygium (group 2), and unexpected OSSN with pterygium found on histopathology (group 3). Clinical charts of patients in groups 2 and 3 were reviewed. MAIN OUTCOME MEASURES: Period prevalence, treatment, and outcome. RESULTS: In surgically excised pterygia, the prevalence of coexistent OSSN was 1.7% (n = 34), of which 41% (n = 14) were clinically suspected preoperatively (group 2) and 59% (n = 20) were unexpectedly found on histopathology (group 3). Clinically suspected OSSN with pterygia was generally treated with wide surgical margins and cryotherapy, whereas unexpected OSSN with pterygia was treated with simple excision, followed by adjuvant interferon treatment in 30% (n = 6). After a mean follow-up of 2 years, there were no recurrences in the suspected OSSN group and 2 recurrences in the unexpected OSSN group. The recurrence rate in the latter group was 11% at 1 year and 24% at 2 years. CONCLUSIONS: Ocular surface squamous neoplasia is uncommonly found to coexist with pterygium. The prognosis in suspected OSSN cases is excellent, with no recurrences noted despite positive margins in 50% of cases. The recurrence rates of unexpected OSSN mirrors that of OSSN not associated with pterygium, and thus vigilance for recurrence is important.

Prevalence of diabetes mellitus in biopsy-positive giant cell arteritis.

BACKGROUND: We tested the hypothesis that patients with diabetes mellitus (DM) develop biopsy-positive giant cell arteritis (GCA) significantly less frequently than nondiabetic patients. METHODS: We compared the prevalence of DM in patients with positive temporal artery biopsy (TAB) with that in patients with negative TAB via a retrospective study of 215 patients who underwent TAB. Patients were classified as having biopsy-positive GCA if microscopic examination disclosed active or healed arteritis. Patients were classified as having DM if they had a diagnosis of diabetes in their medical history or were taking oral hypoglycemic medications and/or insulin at or before the time of biopsy. In addition, we performed a meta-analysis of 8 previously published articles with a total of 1,401 additional biopsy-proven cases of GCA in patients whose status was recorded as diabetic or nondiabetic. RESULTS: Of 44 cases with biopsy-positive GCA in our patient cohort, only 4 (9.1%) were diabetic at or before the time of biopsy. Of 171 patients with negative TAB, 61 (35.7%) had DM (P = 0.0006). The prevalence of DM among recorded cases of biopsy-positive GCA ranged from 0% to 13.8% in the 8 studies included in our meta-analysis, with a combined frequency of 89 diabetic patients in a total of 1,401 cases (6.35%). CONCLUSION: The low frequency of a positive TAB in diabetic GCA suspects should be considered when formulating an index of suspicion in the evaluation of patients with possible GCA. More research is needed to delineate the nature of the interaction between DM and GCA.