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Background: Empirical decisions to select therapies for psoriasis (PSO) and atopic dermatitis (AD) can lead to delays in disease control and increased health care costs. However, routine molecular testing for AD and PSO are lacking. Objective: To examine (1) how clinicians choose systemic therapies for patients with PSO and AD without molecular testing and (2) to determine how often the current approach leads to patients switching medications. Methods: A 20-question survey designed to assess clinician strategies for systemic treatment of AD and PSO was made available to attendees of a national dermatology conference in 2022. Results: Clinicians participating in the survey (265/414, 64% response rate) ranked “reported efficacy” as the most important factor governing treatment choice (P

Background: Mast cells (MCs) have recently been implicated in lymphocytic scarring alopecias, which may share a common pathogenesis. MCs in central centrifugal cicatricial alopecia (CCCA) have not been studied. Objective: We looked for the presence of MCs in CCCA using 2 different stains to see if their numbers correlated with the number of hair follicles, the degree of inflammation and perifollicular fibrosis, disease duration and severity, and patient symptoms. Methods: We performed a retrospective review of biopsies of patients diagnosed with CCCA, tabulated MC counts and correlated them with histopathologic and clinical findings. Results: MC counts were significantly greater using immunoperoxidase staining with CD117 than Giemsa stain, and more were present when the isthmus level was included with the infundibulum. MC counts with CD117 immunostain significantly correlated with the degree of inflammation. MC counts with both stains were significantly associated with the degree of fibrosis independently and after controlling for other factors. Limitations: The study was limited by insufficient tissue remaining in a small number of the transversely cut blocks. Conclusion: Our findings may have therapeutic implications for CCCA and other types of lymphocytic scarring alopecia.

Background and objective: Radiation therapy has increasingly been used in the management of pelvic malignancies. However, the use of radiation continues to pose a risk of a secondary malignancy to its recipients. This study investigates the risk of secondary malignancy development following radiation for primary pelvic malignancies. Methods: A retrospective cohort review of the Surveillance, Epidemiology, and End Results database from 1975 to 2016 was performed. Primary pelvic malignancies were subdivided based on the receipt of radiation, and secondary malignancies were stratified as pelvic or nonpelvic to investigate the local effect of radiation. Key findings and limitations: A total of 2 102 192 patients were analyzed (1 189 108 with prostate, 315 026 with bladder, 88 809 with cervical, 249 535 with uterine, and 259 714 with rectal/anal cancer). The incidence rate (defined as cases per 1000 person years) of any secondary malignancies (including but not limited to secondary pelvic malignancies) was higher in radiation patients than in nonradiation patients (incidence rate ratio [IRR] 1.04, confidence interval [CI] 1.03-1.05), with significantly greater rates noted in radiation patients with prostate (IRR 1.22, CI 1.21-1.24), uterine (IRR 1.34), and cervical (IRR 1.80, CI 1.72-1.88) cancer. While the overall incidence rate of any secondary pelvic malignancy was lower in radiation patients (IRR 0.79, CI 0.78-0.81), a greater incidence was still noted in the same cohorts including radiation patients with prostate (IRR 1.42, CI 1.39-1.45), uterine (IRR 1.15, CI 1.08-1.21), and cervical (IRR 1.72, CI 1.59-1.86) cancer. Conclusions and clinical implications: Except for localized cervical cancer, when put in the context of median overall survival, the impact of radiation likely does not carry enough weight to change practice patterns. Radiation for pelvic malignancies increases the risk for several secondary malignancies, and more specifically, secondary pelvic malignancies, but with a relatively low absolute risk of secondary malignancies, the benefits of radiation warrant continued use for most pelvic malignancies. Practice changes should be considered for radiation utilization in malignancies with excellent cancer-specific survival such as cervical cancer. Patient summary: The use of radiation for the management of pelvic malignancies induces a risk of secondary malignancies to its recipients. However, the absolute risk being low, the benefits of radiation warrant its continued use, and a change in practice patterns is unlikely.

Background: Exposure to maternal inflammation is associated with an increased risk of neurocognitive and developmental disorders in offspring. Early diagnosis and intervention improves childhood motor and cognitive functioning. Neonatal cerebral MRI and remote app-based generalised movement assessments (GMAs) are both predictive of adverse neurocognitive outcomes but have only been used in infants at significantly increased risk for these outcomes, rather than following in utero exposure to maternal inflammatory disorders. Methods: Pregnant women with inflammatory bowel disease were assessed clinically and biochemically in each trimester of pregnancy in this single centre prospective study. Neonatal cerebral MRIs were performed at 6–12 weeks post-corrected term. Two GMA videos were filmed using the ‘BabyMoves’ app from 12 to 16 weeks of age. MRIs and GMAs were assessed by a blinded highly qualified practitioner using validated scoring systems. Results: 40/53 of invited maternal-infant dyads were recruited. C-reactive protein was elevated antenatally in less than 13%. 5/37 neonatal MRIs had incidental or obstetric trauma related gross anatomical abnormalities, with none abnormal on validated gross abnormality scoring. 3/35 GMAs were abnormal, with one GMA abnormality being clinically significant. Of those with abnormal GMAs, 2/3 were in exposed to severely active IBD in-utero. Conclusion: Neonatal cerebral MRI and GMA for neurocognitive screening is feasible in the setting of maternal inflammatory bowel disease, where the risk of cerebral palsy is poorly defined and thus burdensome screening interventions are less appealing to parents. Larger studies are required to stratify adverse neurocognitive outcome risk in infants born to women with maternal inflammatory disorders, but these data are reassuring for women with IBD in remission antenatally.

Background: The liver and lungs are the most common sites of colorectal cancer (CRC) metastases. Their involvement can take five different clinical scenarios: lung metastases only, liver metastases only, lung metastases before liver metastases, liver metastases before lung metastases and simultaneous lung and liver metastases. Using clinical and morphological data we studied the clonal trajectory of these scenarios. Materials and methods: A total of 465 (CRC) patients with 7952 liver and 6406 lung metastases were evaluated. Metastases clinical route was deciphered from metastases number, timing, and linear/parallel ratio (LPR)- a computerized parameter used for deducing clonal trajectories. LPR of +1 suggest pure linear dissemination and −1 pure parallel. Results: Lung-only metastases: high percentage of metachronous disease with a long lead time and a low LPR suggest parallel dissemination. Liver-only metastases: Rare metachronous disease with a short lead time, and a high LPR suggest linear spread. Lung-before-liver metastases: rare solitary metastasis, a median gap of 21 months between the organs, high lung and low liver LPRs suggest linear progression to the lungs and parallel dissemination to the liver. Liver-before-lung metastases: low liver and high lung LPRs and a median gap of 16.5 months between the organs suggest parallel dissemination to the liver and linear spread from the liver to the lungs. Simultaneous liver and lung metastases: rare solitary metastasis and similar and high LPRs suggest simultaneous linear progression to both organs. Conclusions: CRC metastases have different dissemination trajectories in different clinical scenarios. This information can potentially impact on clinical management.

We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer’s disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, expression of pluripotency markers, and maintains a normal karyotype.

Summary: Introduction: Both high- and low-income countries reported increased antibiotic consumption among COVID-19 patients during the first months of the pandemic. To date, however, no studies have examined changes in antibiotic consumption during the COVID-19 pandemic within humanitarian emergency contexts. Method: Data was collected by Médecins Sans Frontières (MSF) for the years 2018–2021 across the following humanitarian settings: Afghanistan (Lashkar Gah), Bangladesh (Kutupalong), the Democratic Republic of Congo (Mweso and Baraka), and South Sudan (Bentiu). Inpatient and outpatient antibiotic consumption was calculated as Daily Defined Dose (DDD) per 1000 inhabitants per day, as per the World Health Organisation's (WHO) Collaborating Centre for Drug Statistics Methodology. Interrupted time series (ITS) analysis, using an autoregressive integrated moving average (ARIMA) model was used to analyse retrospective monthly antibiotic consumption. The impact of COVID-19 pandemic was evaluated as total antibiotic consumption and according to WHO Access, Watch, Reserve (AWaRe) group classifications within each humanitarian setting. Results: The COVID-19 pandemic had no statistically significant impact on total antibiotic consumption in South Sudan (Bentiu) and Bangladesh (Kutupalong). Similarly, the pandemic had no impact on total antibiotic consumption in DR Congo (Baraka), despite an initial 0.27% (estimate=.274, p-value=0.006) increase in March 2020 driven by Access group antibiotics. Meanwhile, total antibiotic consumption in DR Congo (Mweso) and Afghanistan (Lashkar Gah) declined by 0.74% (estimate = −.744, p = 0.003) and 0.26% (estimate = −.26, p < 0.001), respectively with the COVID-19 pandemic. Conclusion: Further studies are required to investigate what may have contributed to these results.

Esophageal dysmotility is identified as a contraindication to lung transplantation at some centers due to increased risks of acute rejection, pulmonary infection, and chronic lung allograft dysfunction. Phosphodiesterase-type 5 inhibitors (PDE5i) are a cornerstone pharmacotherapy for pulmonary arterial hypertension (PAH) and are known to exert off-target effects that may impact lung transplant candidacy, including impaired esophageal contractility and decreased lower esophageal sphincter tone. We report 2 patients with PAH who were initially declined listing for lung transplantation due to iatrogenic esophageal dysmotility induced by PDE5is. Upon discontinuation of PDE5i therapy, these patients experienced significant improvement in esophageal motility within 14 days and met the criteria for transplant listing at their centers. Recognizing and mitigating the off-target effects of PDE5i medications is critical for maximizing access to transplant for patients with PAH.

Disparities in endometrial cancer has increased during the past decade with Black women more likely to be diagnosed at a later stage and have higher mortality. The majority of research has been focused on cultural barriers, socioeconomic status, lack of access to care, comorbidities, and tumor histology to explain these disparities. Limited studies have been conducted on the disparity in the treatment of endometrial intraepithelial neoplasia(EIN). We sought to analyze the differences in treatment used in the management of postmenopausal women with EIN to evaluate whether race/ethnicity is a contributing factor. An IRB approved retrospective study was conducted amongst women at a single institution diagnosed with EIN. Ethnicity/race was defined as non-Hispanic White, non-Hispanic Black, Hispanic, and Asian. Demographic and clinical data was extracted. Multivariable logistic regression was used to examine the association between ethnicity/race and treatment, adjusted for age, BMI, and underlying medical conditions such as cardiovascular disease and diabetes. In total, 254 patients were analyzed. A significant association between ethnicity/race and treatment with non-Hispanic Black women less likely to be treated with surgical management compared to non-Hispanic White women (OR = 0.326, 95 %CI 0.129–0.827, p = 0.026). Importantly, after adjusting for clinical risk factors(age, BMI, CVD, diabetes), non-Hispanic Black women remained at an increased risk of not undergoing surgical intervention (OR = 0.333, 95 % CI 0.125–0.882, p = 0.027). Future research is imperative to evaluate the root cause of this disparity in the healthcare system.

Background: Catheter ablation (CA) for ventricular tachycardia (VT) can be a useful treatment strategy, however, few studies have compared CA to medical therapy (MT) in the sarcoidosis population. Objective: To assess in-hospital outcomes and unplanned readmissions following CA for VT compared to MT in patients with sarcoidosis. Methods: Data was obtained from the Nationwide Readmissions Database between 2010 and 2019 to identify patients with sarcoidosis admitted for VT either undergoing CA or MT during elective and non-elective admission. Primary endpoints were a composite endpoint of inpatient mortality, cardiogenic shock, cardiac arrest and 30-day hospital readmissions. Procedural complications at index admission and causes of readmission were also identified. Results: Among 1581 patients, 1217 with sarcoidosis and VT underwent MT compared to 168 with CA during non-elective admission. 63 patients admitted electively underwent CA compared with 129 managed medically. There was no difference in the composite outcome for patients undergoing catheter ablation or medical therapy during both non-elective (9.0 % vs 12.0 %, p = 0.312) and elective admission (3.2 % vs. 7.8 %, p = 0.343). The most common cause of readmission were ventricular arrhythmias (VA) in both groups, however, those undergoing elective CA were less likely to be readmitted for VA compared to non-elective CA. The most common complication in the CA group was cardiac tamponade (4.8 %). Conclusion: VT ablation is associated with similar rates of 30-day readmission compared to MT and does not confer increased risk of harm with respect to inpatient mortality, cardiogenic shock or cardiac arrest. Further research is warranted to determine if a subgroup of sarcoidosis patients admitted with VT are better served with an initial conservative management strategy followed by VT ablation.

Individuals with congenital heart disease (CHD) have an increased risk of neurodevelopmental impairments. Given the hypothesized complexity linking genomics, atypical brain structure, cardiac diagnoses and their management, and neurodevelopmental outcomes, unsupervised methods may provide unique insight into neurodevelopmental variability in CHD. Using data from the Pediatric Cardiac Genomics Consortium Brain and Genes study, we identified data-driven subgroups of individuals with CHD from measures of brain structure. Using structural magnetic resonance imaging (MRI; N = 93; cortical thickness, cortical volume, and subcortical volume), we identified subgroups that differed primarily on cardiac anatomic lesion and language ability. In contrast, using diffusion MRI (N = 88; white matter connectivity strength), we identified subgroups that were characterized by differences in associations with rare genetic variants and visual-motor function. This work provides insight into the differential impacts of cardiac lesions and genomic variation on brain growth and architecture in patients with CHD, with potentially distinct effects on neurodevelopmental outcomes.

ABSTRACT: Background: Carbapenemase-producing Citrobacter freundii has been reported as a leading cause of healthcare-associated infections. Particularly, C. freundii belonging to the sequence type (ST) 18 is considered to be an emerging nosocomial clone. Objectives: To report the genomic background and phylogenomic analysis of a multidrug-resistant NDM-1-producing C. freundii ST18 (strain CF135931) isolated from an endangered green sea turtle affected by plastic pollution in Brazil. Methods: Genomic DNA was extracted and sequenced using the Illumina NextSeq platform. De novo assembly was performed by CLC Workbench, and in silico analysis accomplished by bioinformatics tools. For phylogenomic analysis, publicly available C. freundii (txid:546) genome assemblies were retrieved from the NCBI database. Results: The genome size was calculated at 5 290 351 bp, comprising 5263 total genes, 4 rRNAs, 77 tRNAs, 11ncRNAs, and 176 pseudogenes. The strain belonged to C. freundii ST18, whereas resistome analysis predicted genes encoding resistance to β-lactams (blaNDM-1, blaOXA-1, blaCMY-117, and blaTEM-1C), aminoglycosides (aph(3′')-Ib, aadA16, aph(3′)-VI, aac(6′)-Ib-cr, and aph(6)-Id), quinolones (aac(6′)-Ib-cr), macrolides (mph(A) and erm(B)), sulphonamides (sul1 and sul2), tetracyclines (tetA and tetD), and trimethoprim (dfrA27). The phylogenomic analysis revealed that CF135931 strain is closely related to international human-associated ST18 clones producing NDM-1. Conclusion: Genomic surveillance efforts are necessary for robust monitoring of the emergence of drug-resistant strains and WHO critical priority pathogens within a One Health framework. In this regard, this draft genome and associated data can improve understanding of dissemination dynamics of nosocomial clones of carbapenemase-producing C. freundii beyond hospital walls. In fact, the emergence of NDM-1-producing C. freundii of global ST18 in wildlife deserves considerable attention.

As summer heat events cause a further increase of heat load in buildings, the need for indoor overheating assessment by building performance simulations (BPS) for planning is rising. Besides other boundary conditions, the selection of proper weather data is known to significantly influence the outcome of overheating evaluation. Our research pointed out that current standards do not consider weather data including regional differences, urban climate effects or future climate in a sufficient way.We suggest a new approach to create weather data sets for an average present and an average future summer based on meteorological data from weather stations. Therefore, we define characteristic summer values as indicators. In addition, urban climate is taken into account by mapping the outdoor temperature differences between urban areas and surrounding countryside using Local Climate Zones. We analyse the developed weather data sets for four regions in Germany by comparing the indoor overheating risk by BPS for an exemplary building. The results show that the overheating risk differs significantly between the regions. It is very low for the region of Hamburg, moderate for Dresden and Potsdam and highly critical for Stuttgart. The indoor heat load is at least more than doubled if the building is located in the city centre instead of its surroundings or if future climate conditions are applied. Furthermore, high night-time outdoor temperatures appear to significantly increase indoor overheating. Our approaches are first suggestions and show the relevance of regional and urban climate for indoor overheating assessment by BPS.

Summary: Background: Approximately 20% of adults in Vietnam have hypertension, and management of this chronic condition remains challenging. This study aimed to assess the effectiveness of a multicomponent intervention in reducing blood pressure (BP) in adults with uncontrolled hypertension. Methods: This cluster randomised controlled trial was conducted in sixteen communities (8 intervention and 8 comparison) in a rural setting in Vietnam (2017–2022). Consenting adults (aged ≥ 18 years) with uncontrolled hypertension were enrolled. Sixteen communities were equally randomised to an intervention or comparison group stratified by district. Consenting adults were assigned to study groups by community. The comparison arm received training sessions about hypertension prevention and management for health workers, and patient education materials. The intervention arm received training sessions about hypertension prevention and management for health workers, and patient education materials and three enhancement components including a storytelling intervention, home BP self-monitoring, and expanded community health worker services. The primary outcome was the difference in changes in patient's levels of systolic BP between the study groups over a 12-month follow-up period. Patients and outcome assessors were masked. Findings: A total of 671 patients (340: intervention, 331: comparison) were enrolled in the trial. The mean age was 66 years and 45% were men. At the 12-month follow-up, the mean systolic BP declined by 18.4 mmHg in the intervention group and 3.7 mmHg in the comparison group (differential decline of 14.7 mmHg [95% CI: 11.8–17.6]). The intervention group also achieved better BP control and medication adherence than the comparison group. There were no serious adverse events related to study participation. Interpretation: The results of this trial demonstrate that a multicomponent intervention can effectively reduce elevated BP in individuals with uncontrolled hypertension in Vietnam. Trial registration: This trial was registered at ClinicalTrials.gov, NCT03590691. Funding: National Heart, Lung, and Blood Institute.

Objective: This study aimed to compare microvascular Doppler sonography (MDS) and laser speckle contrast imaging (LSCI) for assessing vessel patency and aneurysm occlusion during microsurgical clipping of intracranial aneurysms. Methods: MDS and LSCI were used after clip placement during six neurovascular procedures including six patients, and agreement between the two techniques was assessed. LSCI was performed in parallel or right after MDS evaluation. The Doppler response was assessed through listening while flow in the LSCI videos was evaluated by three blinded neurovascular surgeons after the surgery. Statistical analysis determined the agreement between the techniques in assessing flow in 18 regions of interest (ROIs). Results: Agreement between MDS and LSCI in assessing vessel patency was observed in 87 % of the ROIs. LSCI accurately identified flow in 93.3 % of assessable ROIs, with no false positive or negative measurements. Three ROIs were not assessable with LSCI due to motion artifacts or poor image quality. No complications were observed. Conclusions: LSCI demonstrated high agreement with MDS in assessing vessel patency during microsurgical clipping of intracranial aneurysms. It provided continuous, real-time, full-field imaging with high spatial resolution and temporal resolution. While MDS allowed evaluation of deep vascular regions, LSCI complemented it by offering unlimited assessment of surrounding vessels.

Summary: Retinal ganglion cell (RGC) differentiation is tightly controlled by extrinsic and intrinsic factors. Growth and differentiation factor 15 (GDF-15) promotes RGC differentiation, opposite to GDF-11 which inhibits RGC differentiation, both in the mouse retina and in human stem cells. To deepen our understanding of how these two closely related molecules confer opposing effects on retinal development, here we assess the transcriptional profiles of mouse retinal progenitors exposed to exogenous GDF-11 or -15. We find a dichotomous effect of GDF-15 on RGC differentiation, decreasing RGCs expressing residual pro-proliferative genes and increasing RGCs expressing non-proliferative genes, suggestive of greater RGC maturation. Furthermore, GDF-11 promoted the differentiation of photoreceptors and amacrine cells. These data enhance our understanding of the mechanisms underlying the differentiation of RGCs and photoreceptors from retinal progenitors and suggest new approaches to the optimization of protocols for the differentiation of these cell types.

Calcium sulfate powder materials containing terbium ions at 0, 1.0, or 2.0 mol.% were obtained. They are characterized by the presence of a CaSO4 × 0.5H2O phase, while Tb3+ is incorporated into the lattice at ≤1.0 mol.%. Specific surface area enlarged from 2.1 to 22.5 m2/g as crystallite size decreased from 68 to 31 nm. Thermal analysis showed that terbium slightly raises the temperature of CaSO4 × 2H2O-to-CaSO4 transition. Studies of solubility in SBF solution showed the presence of a calcium phosphate layer in terbium-containing cements on the 7th day. Luminescent properties were studied by excitation at 266 nm and 489 nm corresponding to absorption bands of the host and Tb3+ (7F6 - 5D4 absorption band). The recorded emission peaks of the materials showed that the luminescence of the samples was green, with the luminescence intensity increasing when Tb3+ was introduced. The developed materials can find applications in medicine as bioimplants with a possibility of noninvasive visualization of the bone restoration process.

The self-assembly of graphene oxide (GO) and M13 bacteriophage results in the formation of micro-porous structures, known as GraPhage13 aerogels (GPA). Given the limited applications of aerogels in industry due to their nanomechanical properties, along with the previously observed temperature-dependent characteristics in graphene-based nanocomposites, a thorough exploration of the thermosensitive nanomechanical properties of GPA is essential. Herein, a comprehensive characterisation of the morphology, composition, and spectroscopic analysis of the GPA for a range of temperatures has been conducted and correlated with its nanomechanical properties. Elevated temperatures have been found to lead to gradual removal of oxygen-containing functional groups (OCFGs) from GPA, resulting in increased structural defects and reduced stiffness. Notably, unique nanomechanical behaviours of GPA have been further identified, where the thermal expansion of sp3 bonds exceeds that of a crystalline sp3 structure, while the thermal contraction of sp2 bonds in GPA is found to be between graphite and GO. This underscores the impact of GO functionalisation on the thermal expansion behaviour of GPA. The obtained insights enhance the overall comprehension of the temperature annealing impact on GPA and highlight the tunability of its nanomechanical properties, showcasing a broad potential of this novel nanocomposite across a diverse range of applications.

Acute cellular rejection (ACR) is one of the main risk factors for chronic allograft dysfunction, the primary contributor to poor long-term survival in lung transplant recipients. We sought to develop a blood-based transcriptomic risk score (TRS) to detect ACR in lung transplant recipients. We tested for the association of the TRS with ACR in a logistic mixed model. We analyzed 101 samples from 75 individuals. We identified 4 genes after application of the least absolute shrinkage and selection operator. The TRS was significantly associated with ACR (odds ratio (OR) 3.43, 95% confidence interval (CI) 1.86-7.14, p

Uhl anomaly is characterized by the morphologic absence of right ventricular myocardium and is an exceedingly rare cause of nonischemic cardiomyopathy. We report the first case of a successful heart transplantation in a 41-year-old patient who presented in cardiogenic shock from Uhl anomaly causing decompensated right ventricular failure.

Background and purpose: To determine the potential prognostic value of proliferation and angiogenesis plasma proteins following CT-guided high dose rate brachytherapy (HDR-BT) of hepatocellular carcinoma (HCC). Materials and methods: For this prospective study, HDR-BT (1 × 15 Gy) was administered to 24 HCC patients. Plasma was obtained and analyzed using an Olink proteomics Target-96 immuno-oncology-panel that included multiple markers of angiogenesis and proliferation. Fold-change (FC) ratios were calculated by comparing baseline and 48 h post HDR-BT paired samples. Patients were classified as responders (n = 12) if they had no local progression within 6 months or systemic progression within 2 years. Non-responders (n = 12) had recurrence within 6 months and/or tumor progression or extrahepatic disease within 2 years. Results: Proliferation marker EGF was significantly elevated in non-responders compared to responders (p = 0.0410) while FGF-2, HGF, and PlGF showed no significant differences. Angiogenesis markers Angiopoietin-1 and PDGF-B were likewise significantly elevated in non-responders compared to responders (p = 0.0171, p = 0.0462, respectively) while Angiopoietin-2, VEGF-A, and VEGFR-2 did not differ significantly. Kaplan-Meier analyses demonstrated significantly shorter time to systemic progression in patients with increased EGF and Angiopoietin-1 (p = 0.0185, both), but not in patients with one of the remaining proteins elevated (all p > 0.1). Pooled analysis for these 9 proteins showed significantly shorter time to systemic progression for FC ≥1.3 and ≥1.5 for at least 3 proteins elevated (p = 0.0415, p = 0.0193, respectively). Conclusion: Increased plasma levels of EGF and Angiopoietin-1 after HDR-BT for HCC are associated with poor response and may therefore function as predictive biomarkers of outcome.

Purpose: Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery. Design: Preclinical study using a rabbit model of glaucoma filtration surgery. Subjects: Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes. Methods: Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring. Main Outcome Measures: The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology. Results: Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P

Background and Aims: Anxiety over food choices and symptoms related to food consumption diminish quality of life (QoL) in inflammatory bowel disease (IBD) patients. However, the specific factors that impact QoL among IBD patients remain unclear. In this study, we analyzed the relationships of demographic and disease factors with food-related QoL (FRQoL) in a large, diverse US cohort of IBD patients. Methods: In this cross-sectional analysis of 1108 IBD patients aged ≥18 years, we measured FRQoL with the 29-item Food-Related Quality of Life Questionnaire (FR-QoL-29) and disease activity with the Harvey-Bradshaw index in Crohn’s disease (CD) patients or the Simple Clinical Colitis Activity Index in ulcerative colitis (UC) patients. Latinx immigrants completed a Spanish translation of the FR-QoL-29. A subset of patients had colonoscopy and inflammatory marker data available. We used univariate, multivariate, and subgroup analyses to examine the factors that influence FRQoL. Results: In our cohort, 55% of IBD patients self-identified as Latinx. Latinx and non-Latinx patients had similar FR-QoL-29 scores. Female patients had significantly lower FRQoL than male patients (P = .001). Increasing age and IBD duration correlated with higher FRQoL (P < .0001). In UC patients, higher Simple Clinical Colitis Activity Index scores (P < .0001), higher Mayo scores (P = .0009), and longer disease duration (P = .03) predicted significantly lower FRQoL. Disease activity and FRQoL were not significantly related in CD patients. Conclusion: This is the largest study to date to examine FRQoL in American IBD patients, and the first to include Latinx patients. Disease-related factors had a greater impact on FRQoL than ethnicity. Clinical and endoscopic disease activity had a more detrimental impact on FRQoL in UC than in CD. Diet intervention studies are needed to alleviate symptoms and improve FRQoL in the IBD population.

Background: Infants with hypoplastic left heart syndrome (HLHS) or a variant are at risk of ventricular dysfunction (VD) and atrioventricular valve regurgitation (AVVR) prior to superior cavopulmonary connection (SCPC). Although the impact of these complications in isolation has been described, their effect in combination on attrition is poorly defined. Methods: A retrospective observational study of patients with HLHS or variants undergoing a Norwood procedure between 2008 and 2020 at a single center was performed. VD and AVVR were defined as moderate or severe when seen on 2 sequential echocardiograms outside the perioperative period. Attrition was defined as death, listing for heart transplant, or unsuitability for SCPC or transplant. Descriptive statistics and regression models were used for analysis. Results: A total of 397 patients were included, of whom 75% had HLHS and 57% had received a Blalock-Thomas-Taussig shunt. Isolated VD occurred in 9% of patients, AVVR occurred in 13%, and both occurred in 6%. Attrition prior to SCPC occurred in 19% of the overall cohort, in 52% of patients with combined VD and AVVR (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.3-12.0; P

ABSTRACT: The objective of this observational study was to describe variations in partial direct costs of clinical mastitis (CM) treatments among 37 dairy herds using data obtained from herd management records. Animal health and drug purchase records were retrospectively collected from 37 Wisconsin dairy herds for a period of 1 yr. Each farm was visited to verify case definitions, recording accuracy, and detection criteria of CM cases. Descriptive statistics were used to summarize cost of drugs and milk discard. Differences in costs among protocols, intramammary (IMM) products, parities, days in milk, and recurrence were analyzed using ANOVA. Of 20,625 cases of CM, 31% did not receive antimicrobial treatment. The average cost of drugs and milk discard (including cases that were not treated) was $192.36 ± 8.90 (mean ± SE) per case and ranged among farms from $118.13 to $337.25. For CM cases treated only with IMM antimicrobials, milk discard accounted for 87% of total costs and was highly influenced by duration of therapy. Differences in costs were observed among parities, recurrence, and stage of lactation at case detection. Eight different treatment protocols were observed, but 64% of cases were treated using only IMM antimicrobials. Treatment costs varied among protocols; however, cases treated using both IMM and injectable antimicrobials as well as supportive therapy had the greatest costs as they were also treated for the longest duration. Ceftiofur was used for 82% of cases that received IMM antimicrobials while ampicillin was used for 51% of cases treated using injectable antimicrobials. With the exception of ceftiofur and pirlimycin IMM products, many IMM products were given for durations that exceeded the maximum labeled duration. For cases treated using only IMM therapy, as compared with observed costs, we estimated that partial direct costs could be reduced by $65.20 per case if the minimum labeled durations were used. Overall, partial direct costs per case varied among herds, cow factors, and treatment protocols and were highly influenced by the duration of therapy.

Background: To determine if take home laparoscopic trainer boxes with only self-directed learning can develop laparoscopic skills in surgically naive learners. Methods: 74 starting PGY1 OB/Gyn residents and OB/Gyn clerkship medical students volunteered for the study. Learners performed a laparoscopic peg transfer task with only task instructions and no additional training. Initial tasks were recorded and scored. The participants took home a laparoscopic trainer box for 3 weeks to practice without guidance and returned to perform the same task for a second/final score. Initial and final scores were compared for improvement. This improvement was compared to practice and variables such as demographics, surgical interest, comfort with laparoscopy, and past experiences. Results: Mean peg transfer task scores improved from 287 (SD = 136) seconds to 193 (SD = 79) seconds (p

Introduction: Rupture of intracranial aneurysms is the most frequent cause of subarachnoid hemorrhage and is associated with high morbidity. Recommendations for preventive treatment of unruptured aneurysms (UIAs) remain controversial due to inconsistent data on their natural history and the risks associated with treatment. The awareness of being diagnosed with one or more UIAs can provoke feelings of anxiety and psychosocial distress. Therefore, the impact of management on a patients’ health perception and quality of life (QoL) is an essential factor to be considered in the treatment decision-making process. Objective: The aim of this study was to assess and compare QoL in patients diagnosed with one or more UIAs depending on their treatment as well as their pre- or postoperative status. Material and methods: Demographic and clinical data as well as results of the 15D quality of life (15D QoL) questionnaire of 189 patients were prospectively collected and retrospectively analyzed. Patients were categorized into different subgroups, depending on their treatment modalities (conservative, microsurgery or endovascular treatment) and their pre- or postoperative status at the time of completion of the questionnaire. Statistical analysis was performed to compare the different subgroups. Results: Conservatively treated patients had similar mean 15D QoL scores as preoperative patients. Despite an initial postoperative QoL reduction and a trend towards recovery and even an improvement of QoL in the long term after UIA occlusion, neither clinically relevant nor statistically significant differences between preoperative and postoperative mean 15D QoL scores were observed. Conclusions: Health-related QoL does not significantly change after treatment of UIAs when compared to the preoperative period. Further studies are needed to confirm long-term postoperative quality of life changes as well as treatment-related influencing factors on patients’ quality of life.

We evaluated the invasion of plague bacteria Yersinia pestis into a population of black-tailed prairie dogs (Cynomys ludovicianus; BTPDs) in South Dakota. We aimed to ascertain if Y. pestis invaded slowly or rapidly, and to determine if vector (flea) control or vaccination of BTPDs assisted in increasing survival rates. We sampled BTPDs in 2007 (before Y. pestis documentation), 2008 (year of confirmed invasion), and 2009 (after invasion). We estimated annual BTPD re-encounter rates on three 9-ha plots treated annually with deltamethrin dust for flea control and three 9-ha plots lacking dust. In 2007 and 2008, approximately half the adult BTPDs live-trapped were injected subcutaneously with either an experimental plague vaccine (F1–V fusion protein) or placebo formulation; the remaining individuals were not inoculated. From 2007 to 2009, we sampled 1559 BTPDs on 2542 occasions. During 2007–2008, the prevalence and intensity of fleas on BTPDs were 69–97% lower on the dusted vs. no dust plots. From 2007 to 2008, the annual re-encounter rate of non-inoculated BTPDs was 150% higher on the dusted vs. no dust plots. During the same interval on the dusted plots, the re-encounter rate was 55% higher for vaccinated adult female BTPDs vs. nonvaccinated adult females, but the annual re-encounter rate was 19% lower for vaccinated adult males. By late August 2008, BTPDs were nearly extirpated from the no dust plots. During 2007–2008 and 2008–2009 on the dusted plots, which persisted, the BTPD re-encounter rate was 41% higher for vaccinated vs. non-vaccinated adult females but 35% lower for vaccinated adult males. Yersinia pestis erupted with vigor as it invaded. Flea control enhanced BTPD survival but did not offer full protection. Flea control and F1–V vaccination seemed to have additive, positive effects on adult females. Annual re-encounter rates were reduced for vaccinated adult males; additional experimentation is needed to further evaluate this trend.

Summary: The nature and function of perisaccadic receptive field (RF) remapping have been controversial. We use a delayed saccade task to reduce previous confounds and examine the remapping time course in the lateral intraparietal area and frontal eye fields. In the delay period, the RF shift direction turns from the initial fixation to the saccade target. In the perisaccadic period, RFs first shift toward the target (convergent remapping), but around the time of saccade onset/offset, the shifts become predominantly toward the post-saccadic RF locations (forward remapping). Thus, unlike forward remapping that depends on the corollary discharge (CD) of the saccade command, convergent remapping appears to follow attention from the initial fixation to the target. We model the data with attention-modulated and CD-gated connections and show that both sets of connections emerge automatically in neural networks trained to update stimulus retinal locations across saccades. Our work thus unifies previous findings into a mechanism for transsaccadic visual stability.

Purpose: To present a rare case of dedifferentiated liposarcoma of the orbit. Observations: A 61-year-old male complained of left-sided proptosis, diplopia, and limited ocular motility for two years. Biopsy results at that time were suggestive of an atypical lipomatous neoplasm. Ten years later, he presented with increase in size of the mass and worsening of his symptoms. Imaging showed a multi-lobulated mass in the left orbit involving the intraconal, medial, and anterior orbit. Decompression and orbitotomy with biopsy were performed to debulk the mass. Pathology showed a low-grade well-differentiated liposarcoma and the patient was monitored thereafter annually. Eight years later, he complained of persistent proptosis and mass effect from the tumor resulting in ptosis and diplopia and underwent orbital exenteration. Histopathological analysis of the exenterated orbit revealed a focal area of dedifferentiated liposarcoma. Conclusions and importance: Dedifferentiation of an orbital mass can occur as a late complication years after the diagnosis of well-differentiated liposarcoma. Compared to the previously published cases of orbital liposarcoma, this presentation shows a prolonged timeline prior to dedifferentiation (18 years after initial diagnosis). Symptoms of growth or invasive features could indicate dedifferentiation and should warrant a biopsy.

Hydroxyapatite (HA) remains one of the most popular materials for various biomedical applications and its fields of application have been expanding. Lithium (Li+) is a promising candidate for modifying the biological behavior of HA. Li+ is present in trace amounts in the human body as an alkaline and bioelectric material. At the same time, the introduction of Li+ into the HA structure required charge balance compensation due to the difference in oxidation degree, and the scheme of this compensation is still an open question. In the present work, the results of the theoretical and experimental study of the Li+-doped HA synthesis are presented. According to X-ray diffraction data, Fourier transform infrared spectroscopy as well as the combination of electron paramagnetic resonance methods, the introduction of Li+ in the amount up to 0.05 mol% resulted in the preservation of the HA structure. Density functional theory calculations show that Li+ preferentially incorporates into the Ca (1) position with a small geometry perturbation. The less probable positioning in the Ca (2) position leads to a drastic perturbation of the anion channel.

Angiopoietin-like protein 3 (ANGPTL3) is a hepatically secreted protein and therapeutic target for reducing plasma triglyceride-rich lipoproteins and low-density lipoprotein (LDL) cholesterol. Although ANGPTL3 modulates the metabolism of circulating lipoproteins, its role in triglyceride-rich lipoprotein assembly and secretion remains unknown. CRISPR-associated protein 9 (CRISPR/Cas9) was used to target ANGPTL3 in HepG2 cells (ANGPTL3−/−) whereupon we observed ∼50% reduction of apolipoprotein B100 (ApoB100) secretion, accompanied by an increase in ApoB100 early presecretory degradation via a predominantly lysosomal mechanism. Despite defective particle secretion in ANGPTL3−/− cells, targeted lipidomic analysis did not reveal neutral lipid accumulation in ANGPTL3−/− cells; rather ANGPTL3−/− cells demonstrated decreased secretion of newly synthesized triglycerides and increased fatty acid oxidation. Furthermore, RNA sequencing demonstrated significantly altered expression of key lipid metabolism genes, including targets of peroxisome proliferator-activated receptor α, consistent with decreased lipid anabolism and increased lipid catabolism. In contrast, CRISPR/Cas9 LDL receptor (LDLR) deletion in ANGPTL3−/− cells did not result in a secretion defect at baseline, but proteasomal inhibition strongly induced compensatory late presecretory degradation of ApoB100 and impaired its secretion. Additionally, these ANGPTL3−/−;LDLR−/− cells rescued the deficient LDL clearance of LDLR−/− cells. In summary, ANGPTL3 deficiency in the presence of functional LDLR leads to the production of fewer lipoprotein particles due to early presecretory defects in particle assembly that are associated with adaptive changes in intrahepatic lipid metabolism. In contrast, when LDLR is absent, ANGPTL3 deficiency is associated with late presecretory regulation of ApoB100 degradation without impaired secretion. Our findings therefore suggest an unanticipated intrahepatic role for ANGPTL3, whose function varies with LDLR status.

Infectivity assays are essential for the development of viral vaccines, antiviral therapies, and the manufacture of biologicals. Traditionally, these assays take 2–7 days and require several manual processing steps after infection. We describe an automated viral infectivity assay (AVIATM), using convolutional neural networks (CNNs) and high-throughput brightfield microscopy on 96-well plates that can quantify infection phenotypes within hours, before they are manually visible, and without sample preparation. CNN models were trained on HIV, influenza A virus, coronavirus 229E, vaccinia viruses, poliovirus, and adenoviruses, which together span the four major categories of virus (DNA, RNA, enveloped, and non-enveloped). A sigmoidal function, fit between virus dilution curves and CNN predictions, results in sensitivity ranges comparable to or better than conventional plaque or TCID50 assays, and a precision of ∼10%, which is considerably better than conventional infectivity assays. Because this technology is based on sensitizing CNNs to specific phenotypes of infection, it has potential as a rapid, broad-spectrum tool for virus characterization, and potentially identification.

Background: Patients with chronic lymphocytic leukemia (CLL) are immunocompromised and have both a higher incidence of and more aggressive skin cancers, often requiring treatment with Mohs micrographic surgery. Objective: Characterize operative expectations for Mohs surgery in patients with CLL. Methods: Multicenter retrospective cohort study. Results: One hundred fifty-nine tumors from 99 patients with CLL were matched 1:4 with controls. Cases had higher odds for requiring at least 3 stages during Mohs surgery compared to controls (odds ratio = 1.91; 95% CI [1.21-3.02]; P = .01). The mean number of Mohs stages in cases was 1.97 (±0.92) compared with 1.67 (±0.87) in controls (P = .0001). A regression analysis showed that cases had larger postoperative tumor areas (cm2) versus controls (mean = 5.57 vs 4.47; estimate difference Δβ = 1.10 cm2; 95% CI [0.18-2.03]; P = .02). In logistic regression, cases were twice as likely to receive a flap repair compared to controls (odds ratio = 2.45; 95% CI [1.58-3.8]). Limitations: Retrospective cohort study and lack of histologic subtyping of tumors. Conclusion: Patients with CLL require more Mohs stages to attain clear surgical margins, have larger postoperative defect areas, and require more advanced repair techniques compared to a control population without CLL. These findings are essential for preoperative planning and patient counseling and further support the use of Mohs surgery in patients with CLL.

Introduction: Spontaneous intracranial hypotension (SIH) is an important cause of devastating headaches and caused by CSF-leaks in the spine. Research question: The aim of this analysis was to gain an overview of the progress of research on SIH over time. The global publication landscape relating to SIH was analyzed and comparisons between regions were made. Material and methods: A bibliometric analysis was performed by searching for research articles on SIH in PubMed published between 1983 and 2022. Countries responsible for the publications were ranked by the sum of citations. An average annual growth rate was calculated and the density of SIH publications per 100 000 physicians was determined. Results: We identified 974 articles. In 1983 only one SIH patient was reported; in 2021 the number of patients had increased to 4230. The average annual growth rate of SIH publications during this period was 12.7%. The most common publication type were case reports (n = 570). The most common medical specialty of the first author was neurology (n = 251) followed by neurosurgery (n = 250) and radiology (n = 191). Although most publications originated from the United States of America (USA), South Korea had the highest density of SIH investigators (37.86 publications per 100 000 medical doctors). The most cited paper (296 citations) was published in 2006 in JAMA (USA). Discussion and conclusion: Research on SIH has increased exponentially over the past four decades. The international community of SIH researchers is growing, and with it the opportunities for global networks involved in research, treatment, and patient education.

Introduction: Accessing the posterior base of the skull is complex because of the vital neurovascular structures in the area. However, the retrosigmoid approach (RSA) offers a solution to this challenge. Research question: To analyze surgical outcome of RSA. Material and methods: This study involved a retrospective review of patient charts from a single center, focusing on the surgical procedure and outcomes following the operation. Results: The study included 517 patients suffering from conditions like vestibular schwannomas (VS), metastatic cancers, and trigeminal neuralgia. The most frequent symptoms reported were balance disorders (42.7%), hearing loss (36.5%), walking difficulties (21.2%), headaches (18.9%), facial pain (17.1%), issues with trigeminal nerve function (14.1%), cerebellar dysfunction (13.5%), and facial nerve paralysis (10.2%). The rate of complications stood at 21.1%, with 11.3% of patients needing revision surgery. The median score on the Clavien-Dindo scale was 2, and the rate of mortality related to surgery was 1.0%. Permanent symptom improvement was seen in 72.1% of cases. Temporary new deficits occurred in 43.2% of patients, with facial nerve paralysis being the most common (14.1%). No significant correlation was found between the size of the craniotomy and the extent of tumor resection (p = 0.155), except in the case of VS (p = 0.041). Larger craniotomy sizes were associated with higher rates of complications (p = 0.016), especially CSF leaks (p = 0.006). Complications significantly affected the likelihood and number of new deficits (p

Background: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. Objective: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. Methods: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. Results: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8–95.2) and negative predictive value (NPV; 97.8 %, 96.5–98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8–95.5; NPV 99.7 %, 98.3–100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2–40.1), myalgia (8.9, 2.1–38.2) and higher core body temperature (1.9, 1.1–3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. Conclusion: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

Background: Personal care products (PCPs), a source of endocrine-disrupting chemical exposure, may be associated with the risk of hormone-sensitive cancers. Few studies have investigated associations for PCP use with the incidence of hormone-sensitive cancers or considered the joint effect of multiple correlated PCPs. We examined associations between frequently used, or “everyday”, PCPs and incident cancers of the breast, ovary, and uterus with a fucus on the joint effect of multiple product exposure. Methods: Sister Study participants (n=49 899) self-reported frequency of use in the year before enrollment (2003–2009) for 41 PCPs. Using five-level frequency categories based on questionnaire options, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the associations between multiple PCP use and incident breast, ovarian, and uterine cancer using quantile-based g-computation with Cox proportional hazards regression as the underlying model. Multiple PCP use was examined using groupings (beauty, hygiene, and skincare products) determined by both a priori knowledge and Spearman correlation coefficients for co-occurring product use. Associations between individual PCPs and the three cancers were also examined using Cox proportional hazards models coupling with Benjamini-Hochberg procedure for multiple comparisons. Results: Over an average of 11.6 years, 4 226 breast, 277 ovarian, and 403 uterine cancer cases were identified. Positive associations were observed between the hygiene mixture and ovarian cancer (HR=1.35, 95%CI=1.00, 1.83) and the beauty mixture with postmenopausal breast cancer (HR=1.08, 95%CI=1.01, 1.16). Additionally, we observed an inverse association between the skincare mixture and breast cancer (HR=0.91, 95%CI=0.83, 0.99). No significant associations were observed for individual products after corrected for multiple comparison. Conclusions: Findings from this multi-product, joint-effect approach contribute to the growing body of evidence for associations between PCPs and breast cancer and provides novel information on ovarian and uterine cancer.

Summary: Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI −11.4 to 27.8) and 1.7% (95% CI −17.0 to 17.4) at 2–4 and 4–6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0–6, and 6–12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.

Objective: To describe visual acuity data representation in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) Registry and present a data-cleaning strategy Design: Reliability and validity study. Participants: Patients with visual acuity records from 2018 in the IRIS Registry. Methods: Visual acuity measurements and metadata were identified and characterized from 2018 IRIS Registry records. Metadata, including laterality, assessment method (distance, near, and unspecified), correction (corrected, uncorrected, and unspecified), and flags for refraction or pinhole assessment were compared between Rome (frozen April 20, 2020) and Chicago (frozen December 24, 2021) versions. We developed a data-cleaning strategy to infer patients’ corrected distance visual acuity in their better-seeing eye. Main Outcome Measures: Visual acuity data characteristics in the IRIS Registry. Results: The IRIS Registry Chicago data set contains 168 920 049 visual acuity records among 23 001 531 unique patients and 49 968 974 unique patient visit dates in 2018. Visual acuity records were associated with refraction in 5.3% of cases, and with pinhole in 11.0%. Mean (standard deviation) of all measurements was 0.26 (0.41) logarithm of the minimum angle of resolution (logMAR), with a range of − 0.3 to 4.0 A plurality of visual acuity records were labeled corrected (corrected visual acuity [CVA], 39.1%), followed by unspecified (37.6%) and uncorrected (uncorrected visual acuity [UCVA], 23.4%). Corrected visual acuity measurements were paradoxically worse than same day UCVA 15% of the time. In aggregate, mean and median values were similar for CVA and unspecified visual acuity. Most visual acuity measurements were at distance (59.8%, vs. 32.1% unspecified and 8.2% near). Rome contained more duplicate visual acuity records than Chicago (10.8% vs. 1.4%). Near visual acuity was classified with Jaeger notation and (in Chicago only) also assigned logMAR values by Verana Health. LogMAR values for hand motion and light perception visual acuity were lower in Chicago than in Rome. The impact of data entry errors or outliers on analyses may be reduced by filtering and averaging visual acuity per eye over time. Conclusions: The IRIS Registry includes similar visual acuity metadata in Rome and Chicago. Although fewer duplicate records were found in Chicago, both versions include duplicate and atypical measurements (i.e., CVA worse than UCVA on the same day). Analyses may benefit from using algorithms to filter outliers and average visual acuity measurements over time. Financial Disclosure(s): Proprietary or commercial disclosure may be found found in the Footnotes and Disclosures at the end of this article.

Objective: To report the incidence of and evaluate demographic, ocular comorbidities, and intraoperative factors for rhegmatogenous retinal detachment (RRD) and retinal tear (RT) after cataract surgery in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight). Design: Retrospective cohort study. Participants: Patients aged ≥ 40 years who underwent cataract surgery between 2014 and 2017. Methods: Multivariable logistic regression was used to evaluate demographic, comorbidity, and intraoperative factors associated with RRD and RT after cataract surgery. Main Outcome Measures: Incidence and risk factors for RRD or RT within 1 year of cataract surgery. Results: Of the 3 177 195 eyes of 1 983 712 patients included, 6690 (0.21%) developed RRD and 5489 (0.17%) developed RT without RRD within 1 year after cataract surgery. Multivariable logistic regression odds ratios (ORs) showed increased risk of RRD and RT, respectively, among men (OR 3.15; 95% confidence interval [CI], 2.99–3.32; P < 0.001 and 1.79; 95% CI, 1.70–1.89; P < 0.001), and younger ages compared with patients aged > 70, peaking at age 40 to 50 for RRD (8.61; 95% CI, 7.74–9.58; P < 0.001) and age 50 to 60 for RT (2.74; 95% CI, 2.52–2.98; P < 0.001). Increased odds of RRD were observed for procedure eyes with lattice degeneration (LD) (10.53; 95% CI, 9.82–11.28; P < 0.001), hypermature cataract (1.61; 95% CI, 1.06–2.45; P = 0.03), complex cataract surgery (1.52; 95% CI, 1.4–1.66; P < 0.001), posterior vitreous detachment (PVD) (1.24; 95% CI, 1.15–1.34; P < 0.001), and high myopia (1.2; 95% CI, 1.14–1.27; P < 0.001). Lattice degeneration conferred the highest odds of RT (43.86; 95% CI, 41.39–46.49; P < 0.001). Conclusion: In the IRIS Registry, RRD occurs in approximately 1 in 500 cataract surgeries in patients aged > 40 years within 1 year of surgery. The presence of LD conferred the highest odds for RRD and RT after surgery. Additional risk factors for RRD included male gender, younger age, hypermature cataract, PVD, and high myopia. These data may be useful during the informed consent process for cataract surgery and help identify patients at a higher risk of retinal complications. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Summary: Background: As a precursor to gastric cancer, gastric intestinal metaplasia (GIM) represents a target for surveillance. US-based guidelines recommend surveillance of racial/ethnic minorities and immigrants from high incidence gastric cancer regions, yet there is marked variability in prevalence amongst these subgroups and within groups from high incidence regions. There is a paucity of information regarding country of birth as a risk factor for GIM and we sought to determine the association between country of birth and GIM in an ethnically and racially diverse US population. Methods: This was a retrospective cohort study of persons who underwent esophagogastroduodenoscopy (EGD) with gastric biopsy at University of Miami Hospital between 2011 and 2021. A natural language processing (NLP) algorithm was developed and implemented to extract diagnoses of GIM and Helicobacter pylori (HP) infection from endoscopic pathology reports. Multivariable logistic regression was performed to evaluate risk factors for GIM, accounting for important covariates, including country of birth. Findings: A total of 21,108 persons from 130 varying countries of birth were included in the study. A total of 1699 cases of GIM were identified yielding a prevalence of 8.0% (95% CI: 7.7–8.4%). Multivariable analysis was restricted to countries with at least 100 persons in the cohort, yielding 15 countries with 1208 cases of GIM. Country of birth (p

Purpose: The Retinal Ganglion Cell (RGC) Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) consortium was founded in 2021 to help address the numerous scientific and clinical obstacles that impede development of vision-restorative treatments for patients with optic neuropathies. The goals of the RReSTORe consortium are: (1) to define and prioritize the most critical challenges and questions related to RGC regeneration; (2) to brainstorm innovative tools and experimental approaches to meet these challenges; and (3) to foster opportunities for collaborative scientific research among diverse investigators. Design and Participants: The RReSTORe consortium currently includes > 220 members spanning all career stages worldwide and is directed by an organizing committee comprised of 15 leading scientists and physician-scientists of diverse backgrounds. Methods: Herein, we describe the structure and organization of the RReSTORe consortium, its activities to date, and the perceived impact that the consortium has had on the field based on a survey of participants. Results: In addition to helping propel the field of regenerative medicine as applied to optic neuropathies, the RReSTORe consortium serves as a framework for developing large collaborative groups aimed at tackling audacious goals that may be expanded beyond ophthalmology and vision science. Conclusions: The development of innovative interventions capable of restoring vision for patients suffering from optic neuropathy would be transformative for the ophthalmology field, and may set the stage for functional restoration in other central nervous system disorders. By coordinating large-scale, international collaborations among scientists with diverse and complementary expertise, we are confident that the RReSTORe consortium will help to accelerate the field toward clinical translation. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

To assess the spatial heat resilience of buildings in urban development we test the suitability of a toolchain approach from microscale meteorological simulations, resolving the spatial influences on local urban climate, to building performance simulations, evaluating the indoor overheating risk in buildings. This approach makes it possible to investigate how much microscale effects (e.g. buildings, trees e.g. roads) in open space influence the overheating intensity in a building depending on its location within a district. In this context, the question arises how realistic the microscale meteorological simulation is to be used as input for indoor overheating evaluation. In this context, we applied a 3D urban climate model (ENVI-met) and a 1D boundary layer model (HIRVAC) for two urban districts in Germany as meteorological input for an indoor thermal comfort evaluation of two representative buildings. The results demonstrate that ENVI-met simulations without using measured temperature data create unrealistically low diurnal variations in outdoor air temperature despite an overestimated solar irradiance. The implementation to building simulation leads to a significant underestimation of the heat resilience for both buildings and to wrong conclusions about the efficacy of passive heat adaptation measures. In contrast, the HIRVACsimulations show a more realistic representation of the meteorological variables (when measured data is used for calibration) but are not able to resolve urban 3D structures. Our findings point out that an adjusted boundary layer representation in microscale meteorological simulations is crucial to provide meteorological input suitable for realistic spatially resolved indoor overheating analysis.

Olive ridley (Lepidochelys olivacea) turtles migrate across tropical regions of the Atlantic, Pacific, and Indian Oceans. Worryingly, olive ridley populations have been declining substantially and is now considered a threatened species. In this regard, habitat degradation, anthropogenic pollution, and infectious diseases have been the most notorious threats for this species. We isolated a metallo-β-lactamase (NDM-1)-producing Citrobacter portucalensis from the blood sample of an infected migratory olive ridley turtle found stranded sick in the coast of Brazil. Genomic analysis of C. portucalensis confirmed a novel sequence type (ST), named ST264, and a wide resistome to broad-spectrum antibiotics. The production of NDM-1 by the strain contributed to treatment failure and death of the animal. Phylogenomic relationship with environmental and human strains from African, European and Asian countries confirmed that critical priority clones of C. portucalensis are spreading beyond hospital settings, representing an emerging ecological threat to marine ecosystems.

Purpose: The natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation. Methods: 1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test. Results: Median follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p