Influenza transmission dynamics quantified from RNA in wastewater in Switzerland.

INTRODUCTION: Influenza infections are challenging to monitor at the population level due to many mild and asymptomatic cases and similar symptoms to other common circulating respiratory diseases, including COVID-19. Methods for tracking cases outside of typical reporting infrastructure could improve monitoring of influenza transmission dynamics. Influenza shedding into wastewater represents a promising source of information where quantification is unbiased by testing or treatment-seeking behaviours. METHODS: We quantified influenza A and B virus loads from influent at Switzerland's three largest wastewater treatment plants, serving about 14% of the Swiss population (1.2 million individuals). We estimated trends in infection incidence and the effective reproductive number (Re) in these catchments during a 2021/22 epidemic and compared our estimates to typical influenza surveillance data. RESULTS: Wastewater data captured the same overall trends in infection incidence as laboratory-confirmed case data at the catchment level. However, the wastewater data were more sensitive in capturing a transient peak in incidence in December 2021 than the case data. The Re estimated from the wastewater data was roughly at or below the epidemic threshold of 1 during work-from-home measures in December 2021 but increased to at or above the epidemic threshold in two of the three catchments after the relaxation of these measures. The third catchment yielded qualitatively the same results but with wider confidence intervals. The confirmed case data at the catchment level yielded comparatively less precise R_e estimates before and during the work-from-home period, with confidence intervals that included one before and during the work-from-home period. DISCUSSION: Overall, we show that influenza RNA in wastewater can help monitor nationwide influenza transmission dynamics. Based on this research, we developed an online dashboard for ongoing wastewater-based influenza surveillance in Switzerland.

Efficient Transferase Engineering for SAM Analog Synthesis from Iodoalkanes.

S-Adenosyl-l-methionine (SAM) is an important cosubstrate in various biochemical processes, including selective methyl transfer reactions. Simple methods for the (re)generation of SAM analogs could expand the chemistry accessible with SAM-dependent transferases and go beyond methylation reactions. Here we present an efficient enzyme engineering strategy to synthesize different SAM analogs from "off-the-shelf" iodoalkanes through enzymatic alkylation of S-adenosyl-l-homocysteine (SAH). This was achieved by mutating multiple hydrophobic and structurally dynamic amino acids simultaneously. Combinatorial mutagenesis was guided by the natural amino acid diversity and generated a highly functional mutant library. This approach increased the speed as well as the scale of enzyme engineering by providing a panel of optimized enzymes with orders of magnitude higher activities for multiple substrates in just one round of enzyme engineering. The optimized enzymes exhibit catalytic efficiencies up to 31 M-1 s-1, convert various iodoalkanes, including substrates bearing cyclopropyl or aromatic moieties, and catalyze S-alkylation of SAH with very high stereoselectivities (>99 % de). We further report a high throughput chromatographic screening system for reliable and rapid SAM analog analysis. We believe that the methods and enzymes described herein will further advance the field of selective biocatalytic alkylation chemistry by enabling SAM analog regeneration with "off-the-shelf" reagents.

Comparing the latent state-trait structure of the PANSS in cariprazine-medicated and placebo-controlled patients with acute schizophrenia.

After over a hundred years of research, the question whether the symptoms of schizophrenia are rather trait-like (being a relatively stable quality of individuals) or state-like (being substance to change) is still unanswered. To assess the trait and the state component in patients with acute schizophrenia, one group receiving antipsychotic treatment, the other not. Data from four phase II/III, 6-week, randomized, double-blind, placebo-controlled trials of similar design that included patients with acute exacerbation of schizophrenia were pooled. In every trial, one treatment group received a third-generation antipsychotic, cariprazine, and the other group placebo. To assess symptoms of schizophrenia, the Positive and Negative Symptom Scale (PANSS) was applied. Further analyses were conducted using the five subscales as proposed by Wallwork and colleagues. A latent state-trait (LST) model was developed to estimate the trait and state components of the total variance of the observed scores. All symptom dimensions behaved more in a trait-like manner. The proportions of all sources of variability changed over the course of the observational period, with a bent around weeks 3 and 4. Visually inspected, no major differences were found between the two treatment groups regarding the LST structure of symptom dimensions. This high proportion of inter-individual stability may represent an inherent part of symptomatology that behaves independently from treatment status.

Diagnostic potential of exosomal extracellular vesicles in oncology.

Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles (EVs), such as apoptotic bodies, microvesicles, exomeres, and exosomes. Exosomes contain proteins and nucleic acids (DNA/RNA) that can modify the microenvironment and promote cancer progression, playing significant roles in cancer pathology. Clinically, the proteins and nucleic acids within the exosomes from liquid biopsies can be biomarkers for the detection and prognosis of cancer. We review EVs protein and miRNA biomarkers identified for select cancers, specifically melanoma, glioma, breast, pancreatic, hepatic, cervical, prostate colon, and some hematological malignancies. Overall, this review demonstrates that EV biomolecules have great potential to expand the diagnostic and prognostic biomarkers used in Oncology; ultimately, EVs could lead to earlier detection and novel therapeutic targets. Clinical implicationsEVs represent a new paradigm in cancer diagnostics and therapeutics. The potential use of exosomal contents as biomarkers for diagnostic and prognostic indicators may facilitate cancer management. Non-invasive liquid biopsy is helpful, especially when the tumor is difficult to reach, such as in pancreatic adenocarcinoma. Moreover, another advantage of using minimally invasive liquid biopsy is that monitoring becomes more manageable. Identifying tumor-derived exosomal proteins and microRNAs would allow a more personalized approach to detecting cancer and improving treatment.

Exercise-Induced Fluid Retention, Cardiac Volume Overload, and Peripheral Edema in Ultra-Distance Cyclists.

Introduction: Ultracyclists expose themselves to extreme physical challenges. This study aimed to elucidate the effects of ultracycling on electrolyte and fluid balance and investigate the potential occurrence of peripheral edema. Methods: A total of 4 clinical visits were performed before, during, and after a 6-day bicycle ride in 13 ultracyclists (5 female, 8 male) including serial laboratory analyses of blood and urine, bioelectrical impedance, and echocardiography. Throughout the ride, participants continuously tracked fluid intake, measured extremity circumferences daily, and self-tested urinary electrolytes using a point-of-care testing device. Portrait photos were judged by 20 physicians for occurrence of facial and eyelid edema. Results: Participants covered a mean distance of 1205 km and 19,417 vertical meters. From baseline to day 6, body weight remained stable (P = 0.479); however, body composition changed with increasing total body water (TBW) (+1.98 l ± 1.37, P = 0.003) and plasma volume (+18.86 % ± 10.7, P < 0.001). A significant increase in N-terminal pro brain natriuretic peptide (NT-proBNP) (+297.99 ng/l ± 190.42, P < 0.001) until day 6 indicates concomitant cardiac volume overload. Swelling of face and eyelids peaked on day 5 (both P ≤ 0.033). On recovery, changes partly resolved. Although urinary sodium concentration showed a nadir on day 4 (-32.18 mmol/l ± 23.88, P = 0.022), plasma osmolality (+5.69 mmosmol/kg ± 5.88, P = 0.004) and copeptin (+38.28 pg/ml ± 18.90, P < 0.001) increased steadily until day 6. Conclusion: Ultracycling over multiple days induces extracellular volume expansion, peripheral edema, and cardiac volume overload. Renal sodium and water retention is likely contributing to this condition.

α1,3-fucosylation treatment improves cord blood CD34 negative hematopoietic stem cell navigation.

For almost two decades, clinicians have overlooked the diagnostic potential of CD34neg hematopoietic stem cells because of their limited homing capacity relative to CD34posHSCs when injected intravenously. This has contributed to the lack of appeal of using umbilical cord blood in HSC transplantation because its stem cell count is lower than bone marrow. The present study reveals that the homing and engraftment of CD34negHSCs can be improved by adding the Sialyl Lewis X molecule via α1,3-fucosylation. This unlocks the potential for using this more primitive stem cell to treat blood disorders because our findings show CD34negHSCs have the capacity to regenerate cells in the bone marrow of mice for several months. Furthermore, our RNA sequencing analysis revealed that CD34negHSCs have unique adhesion pathways, downregulated in CD34posHSCs, that facilitate interaction with the bone marrow niche. Our findings suggest that CD34neg cells will best thrive when the HSC resides in its microenvironment.

Dietary Exposure to Environmentally Relevant Levels of Chemical Contaminants Reduces Growth and Survival in Juvenile Chinook Salmon.

Chemical pollution can degrade aquatic ecosystems. Chinook salmon in contaminated habitats are vulnerable to health impacts from toxic exposures. Few studies have been conducted on adverse health outcomes associated with current levels and mixtures of contaminants. Fewer still address effects specific to the juvenile life-stage of salmonids. The present study evaluated contaminant-related effects from dietary exposure to environmentally relevant concentrations and mixture profiles in juvenile Chinook salmon from industrialized waterways in the U.S. Pacific Northwest using two end points: growth assessment and disease susceptibility. The dose and chemical proportions were reconstituted based on environmental sampling and analysis using the stomach contents of juvenile Chinook salmon recently collected from contaminated, industrialized waterways. Groups of fish were fed a mixture with fixed proportions of 10 polychlorinated biphenyls (PCBs), 3 dichlorodiphenyltrichloroethanes (DDTs), and 13 polycyclic aromatic hydrocarbons (PAHs) at five concentrations for 35 days. These contaminant compounds were selected because of elevated concentrations and the widespread presence in sediments throughout industrialized waterways. Fork length and otolith microstructural growth indicators were significantly reduced in fish fed environmentally relevant concentrations of these contaminants. In addition, contaminant-exposed Chinook salmon were more susceptible to disease during controlled challenges with the pathogen Aeromonas salmonicida. Our results indicate that dietary exposure to contaminants impairs growth and immune function in juvenile Chinook salmon, thereby highlighting that current environmental exposure to chemicals of potential management concern threatens the viability of exposed salmon.

Digest: The importance of genetic background in bacterial evolution.

How does genetic background influence a population's evolutionary response to an environmental change? Which traits are selected for and how quickly does the population adapt? Filipow et al. (2024) address these questions by exploiting the natural genetic variation of Pseudomonas aeruginosa, a bacterium often found in the lungs of cystic fibrosis patients. They find that while genetic background influences the rate of phenotypic evolution, it does not alter the evolutionary outcome. Their findings contribute to a growing body of work that connects genetic background to future evolvability.

Frequency of Painful Crisis and Other Associated Complications of Sickle Cell Anemia Among Children.

Background Sickle cell disease (SCD) represents a group of inherited health conditions that affect red blood cells. SCD is a relatively common genetic disorder in Saudi Arabia, with the highest prevalence found in the Eastern Province region. The most common complications of SCD include acute chest syndrome, vaso-occlusive crisis, stroke, and avascular necrosis of the femoral head. The disease itself is not a cause of mortality but systemic complications are. Methodology In this retrospective study, we aimed to determine the frequency of painful crisis and the associated complications of sickle cell anemia (SCA) among children at King Saud Medical City (KSMC) in Riyadh, Saudi Arabia. Results This study included a total of 70 children with SCA below the age of 14 years who were admitted to KSMC from January 2021 to December 2021. Overall, 60% of the participants had one painful crisis attack per year, whereas 27% had two attacks. Furthermore, 94% of the participants were being treated with hydroxyurea. The most frequent cause of admission was painful crises with acute chest syndrome. Conclusions This study highlights the frequency of hydroxyurea use among SCA patients. Our results showed that participants who developed one to two painful crises per year were hospitalized for four to nine days on average with increased utilization of hydroxyurea.

Why are different estimates of the effective reproductive number so different? A case study on COVID-19 in Germany.

The effective reproductive number Rt has taken a central role in the scientific, political, and public discussion during the COVID-19 pandemic, with numerous real-time estimates of this quantity routinely published. Disagreement between estimates can be substantial and may lead to confusion among decision-makers and the general public. In this work, we compare different estimates of the national-level effective reproductive number of COVID-19 in Germany in 2020 and 2021. We consider the agreement between estimates from the same method but published at different time points (within-method agreement) as well as retrospective agreement across eight different approaches (between-method agreement). Concerning the former, estimates from some methods are very stable over time and hardly subject to revisions, while others display considerable fluctuations. To evaluate between-method agreement, we reproduce the estimates generated by different groups using a variety of statistical approaches, standardizing analytical choices to assess how they contribute to the observed disagreement. These analytical choices include the data source, data pre-processing, assumed generation time distribution, statistical tuning parameters, and various delay distributions. We find that in practice, these auxiliary choices in the estimation of Rt may affect results at least as strongly as the selection of the statistical approach. They should thus be communicated transparently along with the estimates.

Are Pediatric Residents in Saudi Arabia Equipped to Provide Breastfeeding Care? A Cross-Sectional Study.

Background: There is a progressive reduction in breastfeeding rates in Saudi Arabia. Counseling and support from health-care providers are useful in overcoming barriers to continuing breastfeeding. However, medical education and residency programs often do not adequately provide breastfeeding training. Objective: To determine the knowledge, comfort level, perception, and clinical practices of pediatric residents regarding breastfeeding in Saudi Arabia and to measure the level and type of education received during their residency training. Materials and Methods: This cross-sectional study included pediatric residents from across Saudi Arabia who were registered with the Saudi Commission for Health Sciences and was conducted from February 2021 to January 2022. A validated self-reported questionnaire was used to elicit information from the respondents. Knowledge score was calculated as a percentage of correct answers. Results: A total of 253 residents completed the survey. The mean knowledge score was 58.4% ± 22.7%, which was lower than the cut-off threshold of good knowledge. Almost half of the residents (49.4%) were confident about addressing breastfeeding-related concerns. Although nearly all residents (91.7%) agreed that breastfeeding promotion is part of their role, 35% never or rarely met the mother before birth to discuss breastfeeding. Didactic teaching was the most prevalent educational tool during their training (34.3%); however, most residents preferred learning through interactive workshops (83.7%) and following lactation consultants (82.8%). Conclusion: Despite positive perceptions and confidence in providing breastfeeding care, pediatric residents in Saudi Arabia lack optimal knowledge of breastfeeding. These findings indicate the need for enhancing breastfeeding curricula in pediatric residency programs to improve breastfeeding consultation and management.

The association between the admission to wards with open- vs. closed-door policy and the use of coercive measures.

Introduction: Psychiatric treatment on a ward with open-door policy is associated with reduced numbers of coercive measures. The effect of the door policy of previous stays, however, has not been investigated. Methods: The data set consisted of 22,172 stays by adult inpatients in a psychiatric university hospital between 2010 and 2019. Pairs of consecutive stays were built. The outcome variable was the occurrence of coercive measures during the second stay. Results: Compared to treatments on wards with a closed-door policy at both stays, treatments on wards with an open-door policy at the second stay had smaller odds for coercive measures (OR ranging between 0.09 and 0.33, p < 0.01). In addition, coercive measures were more frequent in treatment histories where patients previously treated on a closed ward were admitted to a ward with an open-door policy and subsequently transferred to a ward with a closed-door policy at the second stay (OR=2.97, p = 0.046). Discussion: Treatment under open-door policy is associated with fewer coercive measures, even in patients with previous experience of closed-door settings. The group of patients who were admitted to a ward with an open-door, then transmitted to a ward with a closed-door policy seem to be prone to experience coercive measures. Clinical strategies to keep these patients in treatment in an open-door setting could further reduce coercive measures.

Sub-Bandgap Sensitization of Perovskite Semiconductors via Colloidal Quantum Dots Incorporation.

By taking advantage of the outstanding intrinsic optoelectronic properties of perovskite-based photovoltaic materials, together with the strong near-infrared (NIR) absorption and electronic confinement in PbS quantum dots (QDs), sub-bandgap photocurrent generation is possible, opening the way for solar cell efficiencies surpassing the classical limits. The present study shows an effective methodology for the inclusion of high densities of colloidal PbS QDs in a MAPbI3 (methylammonium lead iodide) perovskite matrix as a means to enhance the spectral window of photon absorption of the perovskite host film and allow photocurrent production below its bandgap. The QDs were introduced in the perovskite matrix in different sizes and concentrations to study the formation of quantum-confined levels within the host bandgap and the potential formation of a delocalized intermediate mini-band (IB). Pronounced sub-bandgap (in NIR) absorption was optically confirmed with the introduction of QDs in the perovskite. The consequent photocurrent generation was demonstrated via photoconductivity measurements, which indicated IB establishment in the films. Despite verifying the reduced crystallinity of the MAPbI3 matrix with a higher concentration and size of the embedded QDs, the nanostructured films showed pronounced enhancement (above 10-fold) in NIR absorption and consequent photocurrent generation at photon energies below the perovskite bandgap.

Ophthalmic Self-Medication Practices and Associated Factors of Using Steroid Eye Drops Among Adult Ophthalmic Patients.

BACKGROUND: Self-medication is defined as the selection of medicines by individuals to treat self-diagnosed ophthalmic symptoms without consultation of healthcare professionals. Topical steroids can produce severe eye-threatening complications, including the elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage. In recent times, many over-the-counter (OTC) ophthalmic preparations are possible without a prescription. There are a lot of concerns about the safety of long-term use of nonprescription ophthalmic drugs, which may lead to a variety of serious ocular complications. OBJECTIVE: To determine the prevalence of self-medication ocular topical steroid practices and associated factors among adult ophthalmic patients attending ophthalmology clinics at King Saud Medical City (KSMC) in Riyadh. METHODS: A cross-sectional study targeted adults aged 18 or older who had used topical steroids eye drops. The data were collected through interviews, and an online questionnaire was distributed among patients who attended ophthalmology clinics between December 2022 and February 2023. RESULT: From a total of 308 responses, 92 (29.8%) were using ocular topical, 58 (18.8%) with a prescription, five (1.6%) without a prescription, and 29 (9.4%) with and without a prescription, while 216 (70.1%) did not use it. The frequency of using ocular topical steroids without a prescription among participants was 11 (12%) once and 33 (35%) many times. Additionally, 26 (28.3%) were having complications, mostly eye infections (11, 12.4%), glaucoma (8, 9%), and cataracts (6, 6.7%). The reasons for practicing self-medication of steroid eye drops among participants were 14 (15.2%) repeated symptoms, 11 (15.2%) had heard advice from friends, and 11 (15.2%) think they had enough knowledge. CONCLUSION: The study reported the use of self-medication with steroids in ophthalmology clinics at KSMC, even though detecting a high level of perception and acceptable practices among participants. This practice is mainly due to participants having repeated symptoms and thinking they have enough knowledge. Educating the patients would help in reducing the incidence of self-medication steroid eye drops and its associated complications.

COVID-19 outcomes in patients with a history of immune-mediated glomerular diseases.

Introduction: Patients with immune-mediated glomerular diseases are considered at high risk for severe COVID-19 outcomes. However, conclusive evidence for this patient population is scarce. Methods: We created a global registry and retrospectively collected clinical data of patients with COVID-19 and a previously diagnosed immune-mediated glomerular disease to characterize specific risk factors for severe COVID-19 outcomes. Results: Fifty-nine patients with a history of immune-mediated glomerular diseases were diagnosed with COVID-19 between 01.03.2020 and 31.08.2021. Over a mean follow-up period of 24.79 ± 18.89 days, ten patients (16.9%) developed acute kidney injury. Overall, 44.1% of patients were managed in an outpatient setting and therefore considered as having "non-severe" COVID-19, while 55.9% of patients had severe COVID-19 requiring hospitalization including worse outcomes. Comparing both groups, patients with severe COVID-19 were significantly older (53.55 ± 17.91 versus 39.77 ± 14.95 years, p = .003), had lower serum albumin levels at presentation (3.00 ± 0.80 g/dL versus 3.99 ± 0.68 g/dL, p = .016) and had a higher risk of developing acute kidney injury (27% versus 4%, p = .018). Male sex (p <.001) and ongoing intake of corticosteroids at presentation (p = .047) were also significantly associated with severe COVID-19 outcomes, while the overall use of ongoing immunosuppressive agents and glomerular disease remission status showed no significant association with the severity of COVID-19 (p = .430 and p = .326, respectively). Conclusion: Older age, male sex, ongoing intake of corticosteroids and lower serum albumin levels at presentation were identified as risk factors for severe COVID-19 outcomes in patients with a history of various immune-mediated glomerular diseases.

estimateR: an R package to estimate and monitor the effective reproductive number.

BACKGROUND: Accurate estimation of the effective reproductive number ([Formula: see text]) of epidemic outbreaks is of central relevance to public health policy and decision making. We present estimateR, an R package for the estimation of the reproductive number through time from delayed observations of infection events. Such delayed observations include confirmed cases, hospitalizations or deaths. The package implements the methodology of Huisman et al. but modularizes the [Formula: see text] estimation procedure to allow easy implementation of new alternatives to the currently available methods. Users can tailor their analyses according to their particular use case by choosing among implemented options. RESULTS: The estimateR R package allows users to estimate the effective reproductive number of an epidemic outbreak based on observed cases, hospitalization, death or any other type of event documenting past infections, in a fast and timely fashion. We validated the implementation with a simulation study: estimateR yielded estimates comparable to alternative publicly available methods while being around two orders of magnitude faster. We then applied estimateR to empirical case-confirmation incidence data for COVID-19 in nine countries and for dengue fever in Brazil; in parallel, estimateR is already being applied (i) to SARS-CoV-2 measurements in wastewater data and (ii) to study influenza transmission based on wastewater and clinical data in other studies. In summary, this R package provides a fast and flexible implementation to estimate the effective reproductive number for various diseases and datasets. CONCLUSIONS: The estimateR R package is a modular and extendable tool designed for outbreak surveillance and retrospective outbreak investigation. It extends the method developed for COVID-19 by Huisman et al. and makes it available for a variety of pathogens, outbreak scenarios, and observation types. Estimates obtained with estimateR can be interpreted directly or used to inform more complex epidemic models (e.g. for forecasting) on the value of [Formula: see text].

Nationwide evaluation of pancreatic cancer networks ten years after the centralization of pancreatic surgery.

BACKGROUND: Due to centralization of pancreatic surgery, patients with pancreatic cancer are treated in pancreatic cancer networks, composed of referring hospitals (Spokes) and an expert center (Hub). This study aimed to investigate I) how pancreatic cancer networks are organized and II) evaluated by involved clinicians. METHODS: Two online surveys were sent out between January-May 2022. Part I was sent out to the surgical network directors of all hospitals of the Dutch Pancreatic Cancer Group (DPCG). Part II was sent out to all involved clinicians in the Hubs-and-Spokes networks. RESULTS: There was a large variety between the 15 networks concerning number of affiliated Spokes (1-7), annual pancreatoduodenectomies (20-129), and use of a service level agreement (SLA) (40%). More Spoke clinicians considered the Spoke the best location for diagnostic workup (74% vs 36%, P < 0.001). Only 30% of Spoke clinicians attended the Hubs multidisciplinary team meeting frequently. More Hub clinicians thought that exchange of patient information should be improved (37% vs 51%, P = 0.005). CONCLUSION: A large variety in Dutch pancreatic cancer networks was observed concerning number of affiliated Spokes, use of SLAs, and logistic aspects of network care. Improvement of network care concern agreements on diagnostic workup, use of SLA, Spoke participation in the MDT, and patient information exchange.

Sex and gender in infection and immunity: addressing the bottlenecks from basic science to public health and clinical applications.

Although sex and gender are recognized as major determinants of health and immunity, their role is rarely considered in clinical practice and public health. We identified six bottlenecks preventing the inclusion of sex and gender considerations from basic science to clinical practice, precision medicine and public health policies. (i) A terminology-related bottleneck, linked to the definitions of sex and gender themselves, and the lack of consensus on how to evaluate gender. (ii) A data-related bottleneck, due to gaps in sex-disaggregated data, data on trans/non-binary people and gender identity. (iii) A translational bottleneck, limited by animal models and the underrepresentation of gender minorities in biomedical studies. (iv) A statistical bottleneck, with inappropriate statistical analyses and results interpretation. (v) An ethical bottleneck posed by the underrepresentation of pregnant people and gender minorities in clinical studies. (vi) A structural bottleneck, as systemic bias and discriminations affect not only academic research but also decision makers. We specify guidelines for researchers, scientific journals, funding agencies and academic institutions to address these bottlenecks. Following such guidelines will support the development of more efficient and equitable care strategies for all.

Utility of multiparametric renal CT for differentiation of low-grade from high-grade cT1a clear cell renal cell carcinoma.

OBJECTIVE: To determine if CT can differentiate low-grade from high-grade clear cell renal cell carcinoma (ccRCC) in cT1a solid ccRCC. METHODS AND MATERIALS: This retrospective cross-sectional study evaluated 78 < 4 cm solid (>25% enhancing) ccRCC in 78 patients with renal CT within 12 months of surgery between January 2016 and December 2019. Two radiologists (R1/R2), blinded to pathology, independently recorded mass:size, calcification, attenuation and heterogeneity (5-point Likert scale) and recorded a 5-point ccRCC CT Score. Multivariate logistic regression (LR) was performed. RESULTS: There were 64.1% (50/78) low-grade (5/50 Grade 1 and 45/50 Grade 2) and 35.9% (28/78) high-grade (27/28 Grade 3 and 1/28 Grade 4) tumors.Unenhanced CT attenuation was higher (35.9±10.3 R1 and 34.9±10.7 R2 high-grade vs 29.7±10.2 R1 and 29.5±9.8 R2 low-grade, p=0.01-0.02), absolute corticomedullary phase attenuation ratio (CMphase-ratio; 0.67±0.16 R1 and 0.66±0.16 R2 vs 0.93±0.83 R1 and 0.80±0.33 R2, p=0.04-0.05) and 3-tiered stratification of CMphase-ratio (p=0.02) lower in high-grade tumors.A two-variable LR-model including unenhanced CT attenuation and CM.phase-ratio achieved area under the receiver operator characteristic curve of: 73% (95% confidence intervals 59-86%) and 72% (59-84%) for R1 and R2.ccRCC CT score differed by ccRCC grade (p<0.01 R1, R2) with high-grade tumors occurring most commonly in moderately enhancing ccRCC score 4 (46.4% [13/28] R1 and 54% [15/28]). CONCLUSION: Among cT1a ccRCC, high-grade tumors have higher unenhanced CT attenuation and are less avidly enhancing. ADVANCES IN KNOWLEDGE: High-grade ccRCC have higher attenuation (possibly due to less microscopic fat) and lower corticomedullary phase enhancement compared to low-grade tumors. This may result in categorization of high-grade tumors in lower ccRCC diagnostic algorithm categories.

Prospective External Validation of an Algorithm Predicting Hourly Basal Insulin Infusion Rates from Characteristics of Patients with Type 1 Diabetes Treated with Insulin Pumps.

BACKGROUND: We previously published an algorithm predicting 24 h basal insulin infusion profiles in insulin pump-treated subjects with type 1 diabetes profiles from six subject characteristics. This algorithm was to be externally validated in an independent environment and patient population. METHODS: Thirty-two patients with pump-treated type diabetes were switched to their individually algorithm-derived basal insulin infusion profile, and the appropriateness of fasting glycemic control was scrutinized by means of a supervised 24 h fast. Primary endpoint was appropriate fasting glycemic control according to pre-defined criteria in at least 80% of the cohort. RESULTS: In 24 out of 32 patients switching to the algorithm-derived basal insulin infusion rate and undergoing a 24-h fasting period, appropriate glycemic control was achieved (=75%, lower than the pre-defined threshold of 80%), two patients discontinued the fast due to hyperglycemia, and six finished the fasting period, however, with inappropriate fasting glycemic control (entirely due to hyperglycemic episodes). There were no obvious differences in baseline characteristics between those with appropriate vs. inappropriate fasting glycemic control on the basal insulin infusion rate provided by the algorithm. CONCLUSION: In conclusion, when testing fasting glycemic control with an algorithm-derived individual basal insulin infusion profile during a 24 h fasting period in a cohort unrelated in terms of the hospital environment and catchment area, the success rate was lower than a pre-defined threshold for concluding utility of this algorithm. Therefore, applying this algorithm in order to initiate or optimize basal insulin infusion profiles in type 1 diabetes cannot be generally recommended.