Conclusions: With our study, we showed that having an objective perfusion scoring rubric aids in improved PWI interpretation. Although PWI is a powerful tool for CNS lesion diagnosis, methodological radiology evaluation greatly improves the accurate assessment and characterization of tumor recurrence versus treatment effects by all neuroradiologists. Further work should focus on standardizing and validating scoring rubrics for PWI evaluation in tumor patients to improve diagnostic accuracy.Introduction: Imaging surveillance of contrast-enhancing lesions after the treatment of malignant brain tumors with radiation is plagued by an inability to reliably distinguish between tumor recurrence and treatment effects. Magnetic resonance perfusion-weighted imaging (PWI)—among other advanced brain tumor imaging modalities—is a useful adjunctive tool for distinguishing between these two entities but can be clinically unreliable, leading to the need for tissue sampling to confirm diagnosis. This may be partially because clinical PWI interpretation is non-standardized and no grading criteria are used for assessment, leading to interpretation discrepancies. This variance in the interpretation of PWI and its subsequent effect on the predictive value has not been studied. Our objective is to propose structured perfusion scoring criteria and determine their effect on the clinical value of PWI. Methods: Patients treated at a single institution between 2012 and 2022 who had prior irradiated malignant brain tumors and subsequent progression of contrast-enhancing lesions determined by PWI were retrospectively studied from CTORE (CNS Tumor Outcomes Registry at Emory). PWI was given two separate qualitative scores . The first (control) was assigned by a neuroradiologist in the radiology report in the course of interpretation with no additional instruction. The second  was assigned by a neuroradiologist with additional experience in brain tumor interpretation using a novel perfusion scoring rubric. The perfusion assessments were divided into three categories, each directly corresponding to the pathology-reported classification of residual tumor content. The interpretation accuracy in predicting the true tumor percentage, our primary outcome, was assessed through Chi-squared analysis, and inter-rater reliability was assessed using Cohen’s Kappa. Results: Our 55-patient cohort had a mean age of 53.5 ± 12.2 years. The percentage agreement between the two scores was 57.4% (κ: 0.271). Upon conducting the Chi-squared analysis, we found an association with the experimental group reads ( Magnetic resonance imaging (MRI) remains the conventional non-invasive modality in assessing the disease progression and treatment response of central nervous system (CNS) tumors . EmerginOne of the great diagnostic challenges in longitudinal brain tumor management is the differentiation of tumor progression versus treatment effect, particularly in the post-radiation setting. Despite the utilization of many modalities including DWI to distinguish between these two entities, considerable clinical difficulties remain with non-invasive imaging alone. Invasive modalities such as biopsy and/or resection of these lesions for pathologic confirmation remain the only definitive methods of diagnosis in many cases. This inability to reliably identify disease progression affects all aspects of long-term management, resulting in increased imaging frequency and number, delayed initiation of salvage therapy in the setting of recurrence, increased duration of neurological symptoms in certain patients, and interventions such as biopsy and surgical resection to make a correct diagnosis to guide further therapy. The complexity of the underlying pathophysiology as well as variability in how PWI is interpreted can contribute to inconsistencies in PWI results, which in turn may diminish the overall usefulness of these studies. Although PWI has been reported to be a good marker of indicating recurrence ,9, many Given the complexity of perfusion scan interpretations of previously irradiated brain lesions, this study evaluates the utility of a novel PWI scoring rubric created by our group as a supplemental tool for neuroradiologists to improve diagnostic accuracy. The authors aim to assess the validity of the scoring rubric by comparing the study group evaluations to matched pathologic biopsy or tissue resection results at a large tertiary care institution with significant recurrent tumor volume.This retrospective cohort study was conducted at multiple Emory University Healthcare hospitals between 2012 and 2022. The study protocol received approval from the institutional review board at Emory University, and an informed consent waiver was obtained.We collected data from the CNS Tumor Outcomes Registry at Emory (CTORE), a prospectively managed patient outcomes database for central nervous system (CNS) tumors treated at participating sites. The study cohort consisted of patients treated at two tertiary, academic referral hospitals, as well as two mid-sized community hospitals. Our group pooled all patients within the Emory University Hospital system who exhibited suspicion of tumor recurrence in the irradiated area and required re-operation. From this patient population, we included those who had undergone pre-operative perfusion-weighted imaging (PWI) with dynamic susceptibility perfusion (DSC) for data collection and subsequent analyses. The eligibility criteria included patients aged 18 years and older with a history of previously radiated malignant brain tumor and subsequent progression of the contrast-enhancing disease, raising concerns about treatment effects versus tumor recurrence. Specifically, we focused on cases that underwent re-resection following imaging studies of the lesion. All included cases had pre-operative magnetic resonance imaging (MRI) scans, which encompassed PWI evaluation.The cohort was stratified based on patients with a previous history of gliomas or metastasis. The primary outcome of interest was the tumor percentage of the total surgical specimen, as reported by pathology. The pathology reports classified residual tumor contents into three categories: ≤25%, 26–75%, and >75%. These categories were aligned with the corresponding perfusion reads graded by the neuro-radiologists as low, intermediate, and high, respectively.We used electronic medical records to retrospectively collect patient information regarding age, gender, presenting symptoms, pre-operative BMI, pre- and post-operative Karnofsky performance scale (KPS) and modified Rankin scale (MRS), prior systemic therapies, prior radiation dosing and fraction number, post-surgical therapies, post-operative complications, and histopathological findings. Each patient who underwent re-resection had two separate perfusion ratings assigned. The first perfusion rating (the control group) was assigned based on the radiology report generated at the time of pre-operative study evaluation by the neuro-radiology faculty at Emory University School of Medicine. The control group comprised neuroradiologists who subjectively assessed the perfusion levels in the radiology reports available in the electronic medical records. These reports were retrospectively retrieved and analyzed by our research team at CTORE. Based on the text in the radiology report, each study was characterized as high, intermediate, or low perfusion based on the interpretation intended by the initial prospective reader. This classification was subsequently validated by an attending neurosurgeon and a radiology resident, who independently reviewed the electronic medical record interpretations to determine the extent to which the radiologists’ assessments aligned with the progression versus pseudo-progression criteria.The second perfusion rating  was assigned in a blinded retrospective review by a fellowship-trained neuroradiologist, who also played a crucial role in developing the grading rubric for the experimental group. This neuroradiologist employed our novel perfusion scoring rubric  to deterTo account for potential bias in the experimental group, the neuroradiologist evaluating the experimental group was blinded to the control group’s perfusion ratings. Additionally, the same cases were used for both the control and experimental groups to ensure consistency and comparability.Intra-reader agreement was assessed by having the neuroradiologist involved in the experimental group re-read a subset of cases after a certain period to evaluate the consistency of the perfusion scores assigned using the novel perfusion scoring rubric. This additional analysis provides a more sensitive and specific measure to examine the potential effect of the rubric on PWI scoring.Statistical analysis was performed using JMP Pro 16  and R 4.1.3 . Descriptive statistics were performed for pre-, intra-, and post-operative characteristics of our patient cohort as well as all demographic data. For variables that had their normality assumptions met, means with standard deviations were reported; for those that did not meet the normality assumptions, medians with interquartile ranges were reported. p-value. If these assumptions were not met, the two-sided p-value from the Fisher’s exact test was reported. Statistical significance was set at an alpha value of 0.05.A Chi-squared or Fisher’s exact test was performed to assess the accuracy of the non-specialized neuroradiology reads as well as the specialized neuroradiology reads in predicting the true percentage of tumors from the PWI. If the assumptions of the Chi-squared test of at least 80% of cells having an expected value greater than 5 and no cells having an expected value less than 1 were met, we reported the Pearson Inter-rater reliability between the radiologists was calculated using Cohen’s kappa.A total of 55 patients were included in our study after meeting the eligibility criteria. Our patient cohort had a mean age of 53.5 ± 12.2 years , with 32Upon PWI interpretation of the control group , 38 69., 26  patients underwent craniotomies for resection, while 5 (9.1%) patients underwent biopsies. Of the patients who underwent craniotomies, 27 (54.0%) achieved gross-total resection (GTR). Upon histopathological analysis of the biopsied brain tissues, 18 (32.7%) samples had at most 25% tumor, 24 (43.6%) samples had between 26 and 75% tumor, and 13 (23.6%) samples had greater than 75% tumor. p-value: 0.014) and the post-operative tumor content in the pathology report, differentiating between tumor recurrence and treatment effects. In contrast, we observed no association  and the ability to differentiate between tumor recurrence and treatment effects. We further stratified the cohort by the previous history of metastasis or glioma . However, there was no association between the perfusion reads for the experimental group in predicting the tumor percentage stratified by their previous history of metastasis . In comparison, there was no association  or metastasis . After stratifying with 0.5, 1, 1.5, and 2 years, we found no statistically significant evidence that the time between radiation and the perfusion scan predicted the tumor percentage. Upon analysis, we discovered a significant association . Conversely, the experimental group using the grading rubric characterized areas of the lesion as being hypoperfused. Consequently, pathological findings, which were significant for treatment-related effects, coincided with the latter PWI read for the experimental group. Our study demonstrated considerable variation between interpretations of perfusion-weighted imaging provided during the course of normal interpretation without additional guidance versus those provided using a specifically structured rating scale. These ratings differed in their accuracy of assessing recurrent tumor versus treatment effects using PWI, highlighting the need for methodical evaluation of perfusion imaging in the case of previously treated tumors. These results suggest that using a structured grading scale would more reliably predict tumor recurrence, thereby conserving surgical tissue sampling (and its inherent risks) for cases where recurrence is truly present  or only symptomatic radiation necrosis. A standardized grading scale would also better guide systemic and re-irradiation therapies and non-invasively monitor disease progression and the long-term administration of medications such as steroids. After stratification of our data, our hypothesis is supported for the tissue samples of patients with a previous history of glioma but not for metastasis. Our conclusion may be limited by the small sample size of our metastasis cohort, so future studies should focus on assessing whether our grading scale is supported for patients with a history of metastases. This is obviously a cohort where the determination of treatment effect versus tumor recurrence is paramount given the increasing prevalence of brain metastases and widespread radiation treatment. Given the general difficulty in distinguishing treatment effects with recurrent tumors in the immediate post-treatment period (3 months to 1 year after radiation completion), we calculated and stratified the time between the last radiation and time of perfusion scan collected to assess whether this could have affected the prediction of tumor percentage. The incorporation of PWI into the standard follow-up protocol for high-grade patients remains a challenge ,13,14,15Many studies have retrospectivelyand prospectively confirmed the efficacy of PWI in diagnosing tumor recurrence . In partThis study is the first to address such a discrepancy, thus yielding a lower κ value. The PWI analysis performed by the proposed grading criteria could accurately predict tumor recurrence versus treatment effects, similar to previous studies on PWI. Although PWI is a powerful tool for CNS lesion diagnosis, standardized grading criteria must be present in order for PWI to be useful. A limitation is that the grading rubric was used by only a single reader, who likely read these cases with more granularity and care, which may have contributed to the improvement using this method. However, the structured rating scale is easily teachable and can be extended to other readers in the future. We hope to bridge the gap for this disconnect with our grading scale and further generalize our findings through subsequent studies with greater numbers of raters and external validation from other sites.


Transport in porous media plays an essential role for many physical, engineering, biological and environmental processes. Novel synchrotron imaging techniques and image-based models have enabled more robust quantification of geometric structures that influence transport through the pore space. However, image-based modelling is computationally expensive, and end users often require, while conducting imaging campaign, fast and agile bulk-scale effective parameter estimates that account for the pore-scale details. In this manuscript we enhance a pre-existing image-based model solver known as OpenImpala to estimate bulk-scale effective transport parameters. In particular, the boundary conditions and equations in OpenImpala were modified in order to estimate the effective diffusivity in an imaged system/geometry via a formal multi-scale homogenisation expansion. Estimates of effective pore space diffusivity were generated for a range of elementary volume sizes to estimate when the effective diffusivity values begin to converge to a single value. Results from OpenImpala were validated against a commercial finite element method package COMSOL Multiphysics (abbreviated as COMSOL). Results showed that the effective diffusivity values determined with OpenImpala were similar to those estimated by COMSOL. Tests on larger domains comparing a full image-based model to a homogenised  domain that used the effective diffusivity parameters showed differences below 2 % error, thus verifying the accuracy of the effective diffusivity estimates. Finally, we compared OpenImpala’s parallel computing speeds to COMSOL. OpenImpala consistently ran simulations within fractions of minutes, which was two orders of magnitude faster than COMSOL providing identical supercomputing specifications. In conclusion, we demonstrated OpenImpala’s utility as part of an on-site tomography processing pipeline allowing for fast and agile assessment of porous media processes and to guide imaging campaigns while they are happening at synchrotron beamlines.The online version contains supplementary material available at 10.1007/s11242-023-01993-7. Advancements in precision engineering and imaging technologies have enabled studies of porous media in unprecedented detail than ever before. In particular, micro-X-ray computed tomography (XRCT) has shown great promise in enhancing understanding of how pore-scale structures influence mass transport  provides a beneficial avenue to supplement XRCT imaging , which can be potentially subjective. Other methods discretise the images via a pore network modelling approach  for varying elementry volume (EV) sizeUse the time-dependent FEM solver to estimate the error between the effective parameters in the homogenised model and the full image-based modelDetermine time efficiency when using OpenImpala as opposed to the commercial FEM packageWe will start by providing a brief overview of the theoretical framework used in the study. We will then describe the imaged domain used for generating effective parameter estimates for varying EVs. Subsequently, we generate a periodically repeating imaged domain to test the efficacy of the effective parameter. Lastly, we will compare the computational time between OpenImpala and the commercial FEM package and discuss similarities and differences in the context of different scientific disciplines.The dual imaging and diffraction (DIAD) beamline at the diamond light source , it is often more productive and informative to obtain effective transport parameters for a bulk domain rather than include all of the nuanced geometric complexities . For an in-depth derivation, see SI. Considering the diffusion equation:c is dependent X independently we getThe dimensional differential operator can be expanded into a large scale estimate and a small-scale corrector of the spatial derivativeentclass1pt{minimablem Eq. .In this study, we take a detailed pore space segmentation from XRCT scans obtained from the TOMCAT beamline at the Paul Scherrer Institute, Villigen Switzerland Fig. B Daly etx, y, and z directions) and the mean values of all the tensor components. Values obtained for FDM and FEM were compared for the different EVs. Convergence behaviour was also monitored for increasing EVs.The effective parameter is calculated numerically using the finite difference method (FDM) in OpenImpala and the finite element method (FEM) in COMSOL Multiphysics (abbreviated as COMSOL) Multiphysics . For FEMFurthermore, using OpenImpala, we generate a region of interest of a fixed size at ten random locations within the small-scale subdomain. For different fixed sizes, we estimate ensemble means of the effective diffusivity and monitor the variability associated with the different-sized regions of interest.OpenImpala was chosen for the FDM simulations as it is an open-source image-based modelling tool capable of leveraging advantages from HPC infrastructure, such as massive parallelisation  and spatially within each solution. Due to the differences in solution between directions we expect the effective diffusion parameters  for different EV domain sizes Fig. B. The rez et al. ), these Simulations comparing larger domains with heterogeneous structure to the homogenised uniform 1D domains were carried out in COMSOL, as OpenImpala cannot currently carry out time-dependent simulations Fig. . Using tWhile this work has highlighted the utility of OpenImpala for general porous media transport studies, there are still certain restrictions that need to be overcome in the future. OpenImpala can only solve time independent, i.e. stationary, problems. While this was sufficient for estimating the effective diffusivity tensor, OpenImpala was limited in its ability to run verification independently. For a diffusion equation (no convection), an explicit time solver (i.e. Euler time stepping) might be sufficient. However, given the presence of advection, the solver will likely have to consider implicit time stepping approaches, such as Crank-Nicolson Crank and Nicolson .Another major use of multi-scale asymptotic homogenisation in porous media is quantifying hydraulic conductivity or permeability derived from Stokes flow Supplementary file2 (ZIP 1081 KB)Below is the link to the electronic supplementary material.


The spread of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) represents a significant global public health threat. We identified putative risk factors for ESCrE and CRE colonization among patients in 1 urban and 3 rural hospitals in Kenya.During a January 2019 and March 2020 cross-sectional study, stool samples were collected from randomized inpatients and tested for ESCrE and CRE. The Vitek2 instrument was used for isolate confirmation and antibiotic susceptibility testing, and least absolute shrinkage and selection operator (LASSO) regression models were used to identify colonization risk factors while varying antibiotic use measures.P < .001), intubated patients , and persons living with human immunodeficiency virus . CRE colonization odds were higher among patients receiving ceftriaxone  and for every additional day of antibiotic use .Most (76%) of the 840 enrolled participants received ≥1 antibiotic in the 14 days preceding their enrollment, primarily ceftriaxone (46%), metronidazole (28%), or benzylpenicillin-gentamycin (23%). For LASSO models that included ceftriaxone administration, ESCrE colonization odds were higher among patients hospitalized for ≥3 days (odds ratio, 2.32 ; While CRE colonization was strongly associated with ceftriaxone use and duration of antibiotic use, the odds of ESCrE colonization increased with exposure to the hospital setting and invasive medical devices, which may reflect nosocomial transmission. These data suggest several areas where hospitals can intervene to prevent colonization among hospitalized patients, both through robust infection prevention and control practices and antibiotic stewardship programs. The healthcare risk factors for colonization with extended-spectrum cephalosporin-resistant Enterobacterales and carbapenem-resistant Enterobacterales in Kenya highlight the importance of controlling antimicrobial resistance in hospitals, which may be best accomplished through antibiotic stewardship and hospital infection prevention and control interventions. Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae. The spread and impact of antibiotic-resistant bacteria in parts of the world worsened during the coronavirus disease 2019 pandemic [In 2019, an estimated 929 000 global deaths were caused by 6 antibiotic-resistant bacteria and another 3.57 million deaths were attributable to antimicrobial-resistant bacteria [Extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) represent a clinically important group of antibiotic-resistant bacteria given the magnitude of β-lactam use worldwide and few treatment alternatives, particularly in resource-limited settings . Among iAlthough routine antibiotic resistance surveillance systems rely largely on microbiology data from clinically suspected infections, ESCrE and CRE prevalence estimates among bacteria recovered from colonization specimens can provide insights into the prevailing burden of antibiotic resistance and emerging mechanisms of resistance, sometimes before they are recognized as pathogens of clinical concern . FurtherThese data may in turn represent actionable areas to inform hospital prevention and control activities with the goal of reducing transmission of antibiotic-resistant organisms, as envisioned in Kenya's National Action Plan on prevention and containment of antimicrobial resistance . BuildinThis cross-sectional study, which happened between January 2019 and March 2020, was part of the ARCH studies conducted across 6 countries to evaluate the population-based prevalence of colonization with clinically significant antimicrobial-resistant organisms. No deviations were made from the main ARCH protocol, and 3 target microorganisms were investigated. Prevalence data on the target microorganisms , includiOne urban  and 3 rural hospitals  were included in this study. Patients, regardless of age, were selected by simple random sampling from a serialized list of inpatient beds to attain a sample size of 509 rural and 509 urban participants. Patient selection in rural hospitals was proportional to the number of inpatient beds at each hospital . MedicalInformed consent was obtained from adult patients (aged ≥18 years), and adult guardians of unconscious or sedated patients or children <18 years old. Informed assent was also obtained from conscious children aged 7–17 years. Data on potential risk factors for colonization, including duration of hospitalization, admission ward, medical history, invasive procedures, insertion of medical devices, and antibiotic exposure during hospitalization, were abstracted from patient medical records. A stool or rectal swab sample was collected from enrolled individuals per the study protocol, as described elsewhere . SamplesStool and rectal samples were cultured using commercially prepared HardyCHROM extended-spectrum ß-lactamase agar plates and HardyCHROM CRE agar plates. After incubation (18–24 hours at 37°C), up to 3 morphologically distinct colonies were selected from each extended-spectrum ß-lactamase and CRE plate. All isolates were cultured on tryptic soy agar, archived as glycerol stocks, and identified using a Vitek2 instrument with gram-negative (GN) identification cards. Interpretation of minimum inhibitory concentration values from antibiotic susceptibility testing (AST)–GN71 cards was based on the Clinical and Laboratory Standards Institute guidelines, 2020 .Data from the VITEK2 assays were used to classify individuals as ESCrE positive if their stool samples had ≥1 bacterial isolate classified as nonsusceptible (intermediate or resistant) to ceftriaxone but susceptible to the 3 carbapenems tested , and CRE positive if ≥ 1 isolate was classified as nonsusceptible to ≥1 carbapenem.Least absolute shrinkage and selection operator (LASSO) logistic regression models  were useSimilar independent variables, including duration of antibiotic therapy, types of antibiotics administered, comorbid conditions, use of invasive medical devices, history of invasive procedures, patient residence , and duration of hospitalization were retained in each of the 3 models. The duration of the hospital stay was dichotomized from a continuous variable  into a variable indicating whether patient had been admitted for ≥3 days. Additional variable selection information is provided in the xplogit command , which applied the cross-fit partialing-out method (or double machine learning) to estimate the effects of predictor variables and to select from potential control variables to be retained in the model. The xplogit process runs the LASSO estimation across a series of resampled data sets, 10 in our case, using estimates from previous runs to improve subsequent estimation.LASSO regression analysis was used to estimate the effects of putative risk factors on ESCrE and CRE colonization. LASSO regression performs variable selection using a penalty parameter (λ) to “shrink” coefficients that are less relevant to the outcomes  or that exhibit collinearity to zero. This reduces bias issues associated with model overfitting. Models were run using the vce option was used to correct standard errors to account for intragroup correlations. Control variables were included to limit the potential confounding effects of variables on both outcomes and predictors to be weighted in the final estimates [Covariate selection was performed by applying a penalty parameter (λ) to the coefficients of the covariates. To tune λ, a “plugin” estimator was used to determine a value of λ that dominates the noise in the estimating equations to ensure that selected variables had a high probability of belonging to the model . The vcestimates . Data westimates .This study was approved by the Kenyatta National Hospital/University of Nairobi Ethical Review Committee (no. P164/03/2018) with reliance agreements from the Washington State University Institutional Review Board (no. 16742-001), the Kenya Medical Research Institute, and the Centers for Disease Control and Prevention (no. 7111). This project was licensed by the Kenya National Commission for Science, Technology & Innovation (NACOSTI-P-21-12461).A total of 852 participants enrolled at the hospital sites provided a stool sample . Twelve Patients hospitalized for ≥3 days had a higher probability of being ESCrE positive  across all models; patients intubated during the current hospitalization had 1.64–1.73 times higher odds of being ESCrE positive across all models . PatientThe only factor significantly associated with the odds of CRE colonization across all models was the total number of days antibiotics were administered to a patient. Each additional day of antibiotic administration increased the chances of CRE colonization by 1.07–1.08 times . For patThis study sought to identify the drivers of colonization with ESCrE and CRE in the Kenyan hospital context, with the aim of identifying potential areas of intervention to reduce colonization acquisition which can lead to infection and transmission. We observed differences in the importance of non–antibiotic-related risk factors between ESCrE- and CRE-colonized patients. The main risk factors for ESCrE colonization in our study population included primarily non–antibiotic-related risk factors , althougThe higher risk of ESCrE colonization among patients with ≥3 days of hospitalization highlights the importance of the healthcare setting as a risk for colonization. This may represent nosocomial transmission facilitated via patient-to-patient contact, healthcare worker-to-patient contact, or fomites , especiaS. aureus colonization and infection among persons living with HIV [Most literature on HIV and colonization with multidrug-resistant nontuberculous bacteria focuses on high rates of methicillin-resistant with HIV , 26. Evewith HIV , data onwith HIV , 29. Furwith HIV The association between CRE colonization and antibiotic use across all models along with the absence of other associations suggest that CRE colonization may be driven primarily by antibiotic-related sequelae, such as selection pressure for resistant organisms or changes to the microbiome leading to dysbiosis and increased susceptibility to colonization. In our study, the use of ceftriaxone, which can select for CRE , posed tWe acknowledge several limitations of this study. Its cross-sectional nature did not allow us to determine whether ESCrE- or CRE-colonized patients were likely to require longer hospitalization or more antibiotic administration, respectively, or whether these factors contributed to their colonization during hospitalization . Disentangling these relationships will require longitudinal study designs that include other important factors not collected in the current study, such as previous hospitalizations. In addition, despite the inclusion of different hospitals and different wards, we did not collect data on ward-specific or hospital-specific risk factors, which are critical to understanding prevention activities that are broader than those that focus on the patient alone. We did not collect data on HIV control or measures of immunosuppression, so we were unable to evaluate whether the association of ESCrE colonization and HIV positivity was influenced by ART or metrics of HIV severity. Finally, as in most epidemiological studies, the risk factors identified in our study could be surrogates for other causative factors that were not otherwise accounted for.In conclusion, the risk factors for colonization identified in this study—limiting the use of invasive devices, judicious use of antibiotics, and reducing the transmission risk—are similar to those associated with nosocomial infections. This emphasizes not only the importance of infection prevention and control activities but also the utility of colonization data—rather than data on nosocomial infections—in evaluating the effectiveness of hospital interventions. Further research, particularly longitudinal, is needed to parse out the association between HIV and colonization with ESCrE, with attention to measures of disease severity and control . Intervening to prevent colonization with ESCrE and CRE will not only benefit the individual patient, by reducing the risk of infection, but will also help reduce the overall colonization pressure within a facility, leading to decreases in nosocomial transmission more broadly and reduced healthcare costs.Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.ciad258_Supplementary_DataClick here for additional data file.


However, despite significant advancements and increasing expenditure on asthma medications, incidences of asthma-related admissions to hospital and deaths have not improved over the last decade.6 Risk of exacerbations is observed to be even higher when both FeNO and blood eosinophils are raised.6,7 It is proposed that, while FeNO reflects the degree to which blood eosinophils are attracted to the airways, the blood eosinophil count reflects the systemic pool of available eosinophils.8 These two components interact synergistically to increase exacerbation risk  is a non-invasive breath test that provides an objective measure of type-2 airway inflammation, which is typically steroid responsive. Higher FeNO levels have been shown to predict increased risk of acute exacerbations in patients with moderate-to-severe asthma.ion risk .910Stratified analyses of data from randomised controlled trials (RCTs) studying the effectiveness of inhaled corticosteroids (ICS) or biologic therapies in patients with mild, moderate, and moderate-to-severe asthma have shown these treatments to be more effective in patients with biomarkers indicating high levels of type-2 inflammation.11 recommended that FeNO should be used to support diagnosis of asthma. A high FeNO result is reported to have a positive predictive value of 54% to 95% in adults and 90% in school-aged children.12 However, patient-reported symptoms have poor sensitivity and specificity, and published data on peak flow monitoring are unreliable as it is unclear whether monitoring took place when patients were symptomatic.The 2017 National Institute for Health and Care Excellence (NICE) guideline on asthma diagnosis, monitoring, and management13 However, more than half of patients with asthma may have normal spirometry12 and bronchial challenge testing is not readily accessible in primary care.Home peak flow and symptom monitoring, spirometry, and serial bronchial challenge testing in patients with physician-diagnosed asthma recruited from 10 cities across Canada found that around one-third of patients had been incorrectly diagnosed.11 also highlighted the need for more robust evidence to determine the role of FeNO in guiding management of asthma. A systematic review of RCTs comparing FeNO-guided asthma management strategies with other strategies (mainly symptom guided)14 found that the number of patients who experienced an acute exacerbation during follow-up periods lasting 18 to 52 weeks was significantly lower in patients whose management was guided by FeNO; numbers needed to benefit were 12 in adults and 9 in children. However, the implications of these findings for clinical practice are unclear because of the considerable heterogeneity between RCTs in relation to study population characteristics, algorithm decision points , and definitions of acute exacerbations. These factors are highly relevant in determining the extent to which a FeNO-guided algorithm can provide sufficiently different management recommendations and clinical outcomes versus decisions made without FeNO.15The 2017 NICE guideline16 found that adding FeNO to a symptom-guided management strategy did not lead to a significant reduction in acute exacerbations. However, baseline FeNO values of trial participants were typically consistent with low type-2 inflammation, suggesting that opportunities to improve outcomes using a FeNO-guided approach were limited. A post-hoc analysis also found that algorithm recommendations were similar in both arms of the trial, suggesting good correlation between FeNO and symptoms in this study population.A recent RCT conducted in children with asthma who had experienced an acute exacerbation within the last 12 months17 found that, in patients with a low FeNO at baseline, FeNO-guided management was associated with significantly lower ICS consumption and medication costs. However, FeNO-guided management was not associated with any significant changes in asthma control, acute exacerbations, or asthma-related quality of life.A subgroup analysis of data from a primary care trial comparing FeNO- and symptom-guided strategies2 Additionally, avoiding incorrect asthma diagnoses through use of FeNO testing could save the NHS around £32 million.2Although FeNO testing may initially lead to either increased or decreased medication costs when treatment adjustments are made, maintenance costs are likely to be reduced because of fewer follow-up visits and better control of asthma symptoms, resulting in an estimated saving of £114 million in 2023 from using FeNO to optimise asthma treatment.18 The programme included provision of equipment and consumables, two national training modules, and an implementation toolkit, and is estimated to have led to just over half of Primary Care Networks (PCNs) in England now having access to FeNO testing. The National FeNO programme impact report estimated that the programme supported around 58 000 new asthma diagnoses with around two-thirds of FeNO tests being used for diagnostic purposes and around one-third being used for monitoring.18Between April 2021 and March 2023, all 15 Academic Health Sciences Networks (AHSNs) in England delivered a national programme to support introduction and integration of FeNO testing into primary care as part of the NHS England Accelerated Access Collaborative (AAC) Rapid Uptake Products (RUP) Programme.19,20 Patients feel that including FeNO in their routine asthma review would help them understand their asthma better, facilitate more open discussions, and guide more tailored management of their asthma. Clinicians feel that FeNO could be a useful objective measure to help them provide more personalised management plans, educate patients about their asthma,21 and feel more confident about their clinical decisions.20Pilot studies show that children, adults, and clinicians are receptive in principle to using FeNO in primary care and find it to be a feasible and acceptable test.22 FeNO-guided management decisions could potentially lead to a reduction in acute exacerbations in patients with high type-2 inflammation10 and reduced prescribing of asthma medications in patients with low type-2 inflammation without worsening clinical outcomes or quality of life.17Clinicians have been shown to modify patients’ management plans in around one-third of cases after a FeNO result is made available to them. Around 90% of these changes relate to starting, stopping, or adjusting doses of ICS.8Identifying patients with high FeNO results despite high-dose ICS treatment may also lead to earlier referral of patients for consideration of biologic therapies. A FeNO-predominant type-2 inflammation profile is strongly predictive of a positive clinical response to treatments such as dupilumab and tezepelumab, which target airway rather than systemic inflammation.23 Potential barriers to acceptance include increasing complexity of diagnostic and management algorithms and care pathways, and concerns about clinic space requirements.18,23,24 Developing FeNO testing as an additional service may also require existing staff to take on more work, or new staff to be recruited and trained; this may be complicated without sufficient local funding or infrastructure.24Imbalances between institutional recommendations versus established professional practices and standards are well-recognised challenges when introducing new clinical practice guidelines and innovations, including FeNO testing.12 nor NICE11 guidelines recommend that FeNO should routinely be used to monitor patients with asthma. However, NICE recommends that FeNO testing should be considered to support asthma management in patients who have poorly controlled symptoms despite ICS treatment.Additionally, differences between clinical practice guidelines can lead to confusion and non-adherence to recommendations. Neither British Thoracic Society/Scottish Intercollegiate Guidelines Network16 However, non-adherence to both step-up and step-down treatment recommendations generated by a composite type-2 biomarker-guided algorithm in patients with severe asthma led to worse clinical outcomes.25Non-adherence to algorithm recommendations was not found to have implications for numbers of exacerbations in children recruited from a combination of primary and secondary care settings.26 the most common reason for non-adherence in primary care is not stepping down treatment when advised to do so.27Although there is evidence to suggest that FeNO can be used to help guide reductions in ICS treatment without increasing exacerbations in patients with mild-to-moderate asthma,Future research should aim to explore these uncertainties in greater detail, understand how they can be addressed, and provide high-quality evidence to inform clear guidance to inform clinically and cost-effective models for using FeNO to guide asthma management in primary care.18 Asthma + Lung UK’s recent report on timely diagnosis of respiratory conditions24 particularly highlighted the need for Integrated Care Boards (ICBs) to develop and implement strategies to identify local population needs and make plans to ensure that sufficient workforce, equipment, training, and other resources are provided to meet these needs.The National FeNO programme impact report identified the need for strong clinical leadership and long-term infrastructure to provide the financial and logistical resources needed for FeNO testing to be incorporated into clinical pathways for asthma diagnosis and management in primary care.11 was introduced at a time when most general practices did not possess FeNO analysers and were expected to purchase these from their own funds.23 Although the national FeNO programme considerably increased access to relevant equipment and consumables,18 the programme also identified major financial challenges to sustaining this access, including the absence of any ongoing funding or remuneration routes for FeNO testing.The 2017 NICE guideline24 Such initiatives require collaborative working and operational pathways that are tailored according to local needs and availability of resources.Local initiatives designed to support and sustain FeNO testing services include provision of PCN-level respiratory champions, maximising staff resources by training lower-band members of staff to deliver testing and higher-band colleagues to interpret and report findings, setting up of primary care respiratory clinics that may run in a fixed location, rotate around practices, or review patients outside of usual working hours (when there is more space and flexibility), and introduction of referral pathways from primary care to local community hospital clinics that can provide support with diagnosis, treatment advice, and patient education.FeNO testing can potentially provide a non-invasive, feasible way of delivering more personalised asthma management in the community using a ‘treatable traits’ approach. However, more research is needed to develop evidence-based, efficient, sustainable clinical pathways that maximise improvement in clinical decisions and outcomes compared with symptom- or guideline-based strategies. FeNO service delivery models that centralise staff and equipment should be optimised and tailored according to local resource availability and patients’ needs.


Zoster, commonly known as shingles, is a syndrome caused by the reactivation of the varicella-zoster virus (VZV) that results in characteristic vesicular eruptions in a unilateral dermatomal distribution. Timely diagnosis of zoster sine herpete (ZSH), a variant of shingles without the typical vesicular rash, can be challenging due to the absence of visual cues and limited application of traditional diagnostic methods. Recent case reports have demonstrated the utility of VZV DNA polymerase chain reaction (PCR) analysis of involved skin exudates for confirming ZSH. This report presents a case of acute ZSH involving the left trigeminal nerve, where the diagnosis was confirmed using VZV DNA PCR analysis of skin scrapings. The patient initially presented with radicular pain and was treated for presumed shingles, but persistent neuropathic pain persisted. The confirmatory VZV DNA PCR analysis of the involved skin scraping sample aided in establishing the diagnosis of ZSH. The case highlights the potential of using intact skin scrapings for VZV DNA PCR in confirming ZSH. Prompt initiation of antiviral therapy is crucial for minimizing the duration and severity of radicular pain in ZSH cases. Larger studies are needed to further evaluate the utility of VZV DNA PCR analysis for accurately diagnosing ZSH. Zoster, or shingles, is the reactivation of the varicella-zoster virus (VZV) that manifests as clusters of characteristic vesicular eruptions distributed unilaterally in a dermatomal pattern. In the United States, approximately 1 million cases of herpes zoster occur annually as of 2015, approaching a 30% individual lifetime risk -6. In thThe patient was a 74-year-old Hispanic female who presented to our clinic with a complaint of sudden onset constant burning, and hyperesthesia in her left-sided upper facial area, which involved the left scalp, frontal, ophthalmic, and maxillary regions for a few weeks. Prior to the clinic encounter, the patient visited the hospital emergency department one week after the initial onset of symptoms and was prescribed acetaminophen, oxycodone, and valacyclovir for seven days for presumed shingles. Despite these treatments, she experienced persistent neuropathic pain without visible skin findings. The patient had also been seen by a neurologist for a known chronic non-specific neuralgia-type headache and had briefly taken carbamazepine without symptomatic relief, which was then switched to gabapentin 300 mg three times daily. On physical examination, facial skin findings were unremarkable, with an absence of vesicles or erythematous patchy scales. Palpation on the left upper facial area elicited sharp tenderness and a burning sensation. Laboratory tests showed no leukocytosis, a sedimentation rate of 62 mm, and a C-reactive protein level of 0.08 mg/dL. A follow-up neurology visit was made with concerns of worsening neuralgia-type headaches or paroxysmal hemicrania. However, the mentioned diagnoses were deemed unlikely based on the lack of clinical improvement despite the previously described multimodal medical regimen. Upon reassessment, clinical suspicion for presumed post-herpetic neuralgia was raised, and the dosage of gabapentin was subsequently increased to 800 mg three times daily for optimal symptom control. To definitively diagnose VZV involvement, a skin scraping sample was taken from the affected area for VZV DNA PCR, which yielded a positive result. The serum varicella zoster IgM antibody test, however, was negative. With the confirmed diagnosis of ZSH based on the skin sample, the patient was prescribed 3% lidocaine topical cream as needed, in addition to continuing with gabapentin. Over a few weeks, her radicular pain gradually improved, as observed during repeat cranial nerve examinations at subsequent close follow-up visits. The patient was also referred to an ophthalmologist, who confirmed the absence of herpes zoster ophthalmicus.Zoster sine herpete is a condition characterized by radicular pain along a dermatomal distribution without the presence of an erythematous or vesicular rash, which is typical of shingles . The diaRecent case reports have demonstrated the utility of VZV DNA PCR analysis of involved skin exudates in diagnosing ZSH. These cases involved vesicles or open skin lesions from vesicular eruptions that were subjected to PCR analysis, confirming the diagnosis of herpes zoster -6. HowevOur patient presented with isolated radicular pain along a dermatomal distribution of the left trigeminal nerve without the characteristic herpetic rash. The patient received early antiviral therapy for a presumed shingles infection, and later the diagnosis of ZSH was confirmed when VZV DNA PCR of the involved skin scraping sample yielded a positive result. Our case illustrates that scraping intact skin samples from the affected area, even without any exudates or open vesicles, can be used to confirm ZSH. Although the diagnosis of ZSH requires confirmatory testing, antiviral therapy against VZV should be initiated as soon as clinical suspicion for ZSH arises to minimize the duration and severity of radicular pain.