Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting.

BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

Case report: Unilateral panuveitis as a manifestation of Alport syndrome in a Chinese pediatric patient.

Purpose: The study aimed to report a rare case of a patient with Alport syndrome, which was manifested as unilateral non-infectious uveitis after bilateral cataract surgery. Methods: A case report. Results: A 2-year-old boy was diagnosed with unilateral panuveitis based on the clinical and multimodal imaging findings. Intraocular fluid samples for metagenomic next-generation sequencing (mNGS) and microbial culture were negative. However, urine tests found proteinuria and microscopic hematuria. Pathologic findings of the kidney revealed a thickened membrane, and a diagnosis of Alport syndrome was considered. Gene analysis found deletions in exon 1 of COL4A5 and exons 1 and 2 of COL4A6. The uveitis resolved gradually, following the administration of oral steroids. Conclusion: Uveitis may be an ocular manifestation of Alport syndrome.

A robust, low-cost instrument for real-time colorimetric isothermal nucleic acid amplification.

The COVID-19 pandemic has highlighted the need for broader access to molecular diagnostics. Colorimetric isothermal nucleic acid amplification assays enable simplified instrumentation over more conventional PCR diagnostic assays and, as such, represent a promising approach for addressing this need. In particular, colorimetric LAMP (loop-mediated isothermal amplification) has received a great deal of interest recently. However, there do not currently exist robust instruments for performing these kinds of assays in high throughput with real-time readout of amplification signals. To address this need, we developed LARI, the LAMP Assay Reader Instrument. We have deployed over 50 LARIs for routine use in R&D and production environments, with over 12,000 assays run to date. In this paper, we present the design and construction of LARI along with thermal, optical, and assay performance characteristics. LARI can be produced for under $1500 and has broad applications in R&D, point-of-care diagnostics, and global health.

Quantitative Evaluation of Retinal Microvascular Abnormalities in Patients With Type 2 Diabetes Mellitus Without Clinical Sign of Diabetic Retinopathy.

Purpose: To evaluate microvascular abnormalities in the macula and peripapillary area in diabetic patients without clinical signs of diabetic retinopathy (DR) and compare them with healthy control eyes, using optical coherence tomography angiography (OCTA). Methods: A prospective study was performed of 49 eyes from 49 diabetic patients without clinical signs of DR and a control group of 52 eyes from 52 healthy normal individuals. The 3 × 3 mm macular scans and 4.5 × 4.5 mm optic disc scans were obtained with the OCTA RTVue-XR Avanti system. Angiograms from the superficial capillary plexus, the deep capillary plexus of the macula scans, and radial peripapillary capillary plexus of the optic disc scans were analyzed with MATLAB. Multivariate binary logistic regression and the least absolute shrinkage and selection operator (LASSO) regression were used to select ideal parameters that distinguish diabetic eyes without DR from normal eyes. A receiver operating characteristic (ROC) curve was generated, and sensitivity and specificity were calculated. Results: Our final model identified FD-300 (foveal vessel density in a 300-µm-wide region around foveal avascular zone) as the only parameter selected by both the LASSO regression and the final multivariate logistic regression model that significantly differentiates diabetic eyes without clinical signs of DR from healthy normal eyes. The area under the ROC curve of FD-300 was 0.685, and sensitivity and specificity were 65.3% and 71.2%, respectively. Conclusions: Quantitative evaluation of retinal microvascular abnormalities using OCTA identified FD-300 as a useful biomarker versus the other macular and peripapillary OCTA metrics in the early detection of preclinical diabetic retinal abnormalities. Translational Relevance: OCTA may be useful in detecting early retinal microvascular abnormalities in diabetic patients before the clinical findings of DR become visible.

Case Report: Multimodal Imaging of Acute Idiopathic Maculopathy in a Chinese Woman.

SIGNIFICANCE: Acute idiopathic maculopathy is a rare disease with the characteristics of sudden, severe, unilateral central vision loss after a flu-like illness. The prognosis is generally good, and poor vision usually results from complications such as choroidal neovascularization or subfoveal pigment degeneration. Multimodal imaging is helpful in the diagnosis and follow-up of this disease. PURPOSE: We report a case of acute idiopathic maculopathy and present multimodal imaging results in the diagnosis of this condition. CASE REPORT: A 37-year-old Chinese woman noted a central scotoma in her right eye a day after a prodrome of flu-like symptoms. Best-corrected visual acuity of the right eye was 20/40. Multimodal imaging was performed, and a diagnosis of acute idiopathic maculopathy was made. The variable clinical appearance of acute idiopathic maculopathy on autofluorescence, near-infrared reflectance, and optical coherence tomography (OCT) was shown. The patient's vision spontaneously recovered to 20/20 two weeks after the onset of the disease, but macular sensitivity, as measured by microperimetry, did not return to normal until 1 month. Retrobulbar injection of triamcinolone was done at 3 weeks to prevent retinal pigment epithelium hyperplasia and choroidal neovascularization. Written informed consent was obtained from the patient. CONCLUSIONS: Our findings suggest that near-infrared reflectance corresponds to the change of the outer retina and retinal pigment epithelium on OCT and complements autofluorescence in the diagnosis and follow-up of acute idiopathic maculopathy. Fundus autofluorescence, near-infrared reflectance, and OCT are recommended as routine examinations in this disease.

Detection of the Microvascular Changes of Diabetic Retinopathy Progression Using Optical Coherence Tomography Angiography.

Purpose: To investigate microvascular parameters that are related to the severity of diabetic retinopathy (DR) with optical coherence tomography angiography (OCTA). Methods: In total, 105 eyes from 105 diabetic patients were recruited in this prospective cross-sectional study, including 37 eyes with no clinical signs of DR (NoDR), 43 eyes with nonproliferative diabetic retinopathy (NPDR), and 25 eyes with proliferative diabetic retinopathy (PDR). Angiogram images from the parafoveal superficial capillary plexus (SCP), the deep capillary plexus (DCP), and the radial peripapillary capillary plexus were analyzed, and metrics were compared among groups. Multivariate regression analysis was used to identify the best OCTA parameters that could distinguish DR severity among groups. Results: Parafoveal vessel diameter index in the SCP and vessel density (VD) in the DCP showed the strongest correlation with the severity of DR (P < 0.01). Extrafoveal avascular area in the SCP was the parameter that could most distinguish NoDR from NPDR (P < 0.01) with sensitivity and specificity of 83.72% and 78.38%, respectively. VD in the DCP also was the most sensitive biomarker to distinguish NPDR from PDR (P < 0.01) with sensitivity and specificity of 84.00% and 79.07%, respectively. Conclusions: The microvascular changes in the SCP and DCP in DR may have different characteristics that could be identified with specific OCTA parameters. OCTA serves as a promising technology to discriminate eyes with different severity of DR. Translational Relevance: Our study investigated OCTA metrics and severity of DR. At different stages of DR, ophthalmologists may focus on specific OCTA parameters to predict the progression of retinopathy in individual patients.

Case Report: Adult Retinoblastoma Progression in 19 Months.

SIGNIFICANCE: Retinoblastoma is the most common intraocular malignancy in childhood, comprising 4% of all pediatric cancers. Adult onset is extremely rare. Enucleation is usually performed in adult cases because of the atypical presentations and malignant features of the tumor, which lead to misdiagnosis. PURPOSE: We report a case of a 34-year-old woman who presented with an intraocular mass that was present for 19 months without any treatment before enucleation. CASE REPORT: A 34-year-old woman with a history of a dark shadow in her right eye for 2 weeks presented with a whitish-pink mass in the nasal superior retina. Angiography revealed leakage of vessels on the surface of the tumor. Ultrasound showed a midrange echogenic mass in the right eye. The patient denied treatment and was not seen again until 19 months after her first visit. B-scan ultrasound showed enlargement of intraocular growth without calcification. The patient subsequently underwent enucleation, and retinoblastoma was confirmed with histopathology of the enucleated eye. CONCLUSIONS: Retinoblastoma in adulthood is very rare. It has different clinical characteristics that need to be differentiated from other retinal tumors, such as primitive neuroectodermal tumor. They can develop very fast, but needle biopsy is not recommended. Eye care practitioners should be aware of the possibility of this malignancy in adults.

Public Health Role of Academic Medical Center in Community Outbreak of Hepatitis A, San Diego County, California, USA, 2016-2018.

During 2016-2018, San Diego County, California, USA, experienced one of the largest hepatitis A outbreaks in the United States in 2 decades. In close partnership with local healthcare systems, San Diego County Public Health led a public health response to the outbreak that focused on a 3-pronged strategy to vaccinate, sanitize, and educate. Healthcare systems administered nearly half of the vaccinations delivered in San Diego County. At University of California San Diego Health, the use of informatics tools assisted with the identification of at-risk populations and with vaccine delivery across outpatient and inpatient settings. In addition, acute care facilities helped prevent further disease transmission by delaying the discharge of patients with hepatitis A who were experiencing homelessness. We assessed the public health roles that acute care hospitals can play during a large community outbreak and the critical nature of ongoing collaboration between hospitals and public health systems in controlling such outbreaks.

The Effect of Clostridioides difficile Diagnostic Stewardship Interventions on the Diagnosis of Hospital-Onset Clostridioides difficile Infections.

BACKGROUND: Public reporting of Clostridioides difficile infection (CDI) using laboratory-identified events has led some institutions to revert from molecular-based tests to less sensitive testing modalities. At one academic medical center, researchers chose to use nucleic acid amplification test alone in CDI diagnosis with institutional protocols aimed at diagnostic stewardship. METHODS: A single-center, quasi-experimental study was conducted to introduce and analyze the effects of various diagnostic stewardship interventions. In April 2017 an order report was created to inform providers of patients' recent bowel movements, laxative use, and prior Clostridioides difficile (CD) testing (Intervention 1). In November 2017 nursing staff were empowered to not send nondiarrheal stools for testing (Intervention 2). In February 2019, an interruptive alert was implemented to prevent testing that was not indicated (Intervention 3). CD testing rates and healthcare facility-onset CDI (HO-CDI) rates were compared before and after the interventions using one-way analysis of variance (ANOVA). RESULTS: At baseline, testing for CD after 3 days of admission was performed at mean ± standard deviation of 15.9 ± 1.7 tests/1,000 patient-days. After Intervention 1, it decreased to 12.1 ± 1.1 tests. This further decreased to 10.6 ± 0.8 after Intervention 2 and to 8.1 ± 0.1 after Intervention 3 (p < 0.001). HO-CDI cases per 10,000 patient-days declined from 12.7 ± 1.4 cases at baseline to 10.7 ± 1.2 after Intervention 1, to 8.7 ± 2.4 after Intervention 2, and to 5.8 ± 0.2 after Intervention 3 (p = 0.03). CONCLUSION: A multidisciplinary approach optimizing electronic health record support tools and leveraging nursing education can reduce both testing and HO-CDI rates while using the most sensitive testing modality.

Evaluation of the National Healthcare Safety Network standardized infection ratio risk adjustment for healthcare-facility-onset Clostridioides difficile infection in intensive care, oncology, and hematopoietic cell transplant units in general acute-care hospitals.

OBJECTIVE: To evaluate the National Health Safety Network (NHSN) hospital-onset Clostridioides difficile infection (HO-CDI) standardized infection ratio (SIR) risk adjustment for general acute-care hospitals with large numbers of intensive care unit (ICU), oncology unit, and hematopoietic cell transplant (HCT) patients. DESIGN: Retrospective cohort study. SETTING: Eight tertiary-care referral general hospitals in California. METHODS: We used FY 2016 data and the published 2015 rebaseline NHSN HO-CDI SIR. We compared facility-wide inpatient HO-CDI events and SIRs, with and without ICU data, oncology and/or HCT unit data, and ICU bed adjustment. RESULTS: For these hospitals, the median unmodified HO-CDI SIR was 1.24 (interquartile range [IQR], 1.15-1.34); 7 hospitals qualified for the highest ICU bed adjustment; 1 hospital received the second highest ICU bed adjustment; and all had oncology-HCT units with no additional adjustment per the NHSN. Removal of ICU data and the ICU bed adjustment decreased HO-CDI events (median, -25%; IQR, -20% to -29%) but increased the SIR at all hospitals (median, 104%; IQR, 90%-105%). Removal of oncology-HCT unit data decreased HO-CDI events (median, -15%; IQR, -14% to -21%) and decreased the SIR at all hospitals (median, -8%; IQR, -4% to -11%). CONCLUSIONS: For tertiary-care referral hospitals with specialized ICUs and a large number of ICU beds, the ICU bed adjustor functions as a global adjustment in the SIR calculation, accounting for the increased complexity of patients in ICUs and non-ICUs at these facilities. However, the SIR decrease with removal of oncology and HCT unit data, even with the ICU bed adjustment, suggests that an additional adjustment should be considered for oncology and HCT units within general hospitals, perhaps similar to what is done for ICU beds in the current SIR.

A Smartphone-Based Tool for Rapid, Portable, and Automated Wide-Field Retinal Imaging.

PURPOSE: High-quality, wide-field retinal imaging is a valuable method for screening preventable, vision-threatening diseases of the retina. Smartphone-based retinal cameras hold promise for increasing access to retinal imaging, but variable image quality and restricted field of view can limit their utility. We developed and clinically tested a smartphone-based system that addresses these challenges with automation-assisted imaging. METHODS: The system was designed to improve smartphone retinal imaging by combining automated fixation guidance, photomontage, and multicolored illumination with optimized optics, user-tested ergonomics, and touch-screen interface. System performance was evaluated from images of ophthalmic patients taken by nonophthalmic personnel. Two masked ophthalmologists evaluated images for abnormalities and disease severity. RESULTS: The system automatically generated 100° retinal photomontages from five overlapping images in under 1 minute at full resolution (52.3 pixels per retinal degree) fully on-phone, revealing numerous retinal abnormalities. Feasibility of the system for diabetic retinopathy (DR) screening using the retinal photomontages was performed in 71 diabetics by masked graders. DR grade matched perfectly with dilated clinical examination in 55.1% of eyes and within 1 severity level for 85.2% of eyes. For referral-warranted DR, average sensitivity was 93.3% and specificity 56.8%. CONCLUSIONS: Automation-assisted imaging produced high-quality, wide-field retinal images that demonstrate the potential of smartphone-based retinal cameras to be used for retinal disease screening. TRANSLATIONAL RELEVANCE: Enhancement of smartphone-based retinal imaging through automation and software intelligence holds great promise for increasing the accessibility of retinal screening.

Ketamine: A Cause of Urinary Tract Dysfunction.

Drug addiction as a result of improper use of prescribed and illicit use has been on the increase globally. The effects of such use have implications in the urologic disease space. To this end, Ketamine has been reported to affect urologic function, causing a number of voiding symptoms. It may also confound the differential diagnosis of urologic diseases, such as interstitial cystitis, among others.

Emphysematous pyelonephritis: the impact of urolithiasis on disease severity.

BACKGROUND: Emphysematous pyelonephritis is a severe infection of the kidney associated with formation of gas in the renal parenchyma and/or collecting system. The purpose of this study was to evaluate outcomes of patients with emphysematous pyelonephritis in a contemporary cohort and to evaluate the impact of urolithiasis on disease severity. METHODS: A search of all imaging reports at University of California San Francisco (UCSF) for the term "emphysematous pyelonephritis" was undertaken from 2003-2014. Patients were included if there was clinical evidence of infection, no recent urologic instrumentation, and computerized tomography (CT) demonstrating gas in the renal parenchyma or collecting system. Clinical and laboratory variables were obtained from medical records. RESULTS: A total of 14 cases were identified. The majority of patients (57%) had gas confined to the collecting system. Three patients (21%) had gas in the renal parenchyma and 3 patients (21%) had gas extending into perirenal tissues. A total of 8 patients (57%) had concomitant urolithiasis. Seven patients (50%) were managed with antibiotic therapy alone while 6 patients (43%) required percutaneous drainage. No patients required immediate nephrectomy. There were no deaths. Patients with urolithiasis had less severe emphysematous pyelonephritis than patients without urolithiasis (P<0.05). CONCLUSIONS: The majority of patients in this study had gas contained within the collecting system and were treated successfully with antibiotics alone. Percutaneous drainage was successfully utilized in patients with more advanced disease. No patients required emergent nephrectomy. Emphysematous pyelonephritis in patients with urolithiasis was less severe than in patients without urolithiasis.

Standardized Infection Ratio for Surgical Site Infection after Colon Surgery: Discord in Models Measuring Healthcare Quality.

The government publishes 3 different public report surgical site infection (SSI) metrics, all called standardized infection ratios (SIRs), that impact perceived hospital quality. We conducted a non-random cross-sectional observational pilot study of 20 California hospitals that voluntarily submitted colon surgery and SSI data. Discordant SIR values, leading to contradictory conclusions, occurred in 35% of these hospitals. Infect Control Hosp Epidemiol 2016;1-5.