Novel Clinical, Immunological, and Metabolic Features Associated with Persistent Post-Acute COVID-19 Syndrome.

The coronavirus disease 2019 (COVID-19) survivors are frequently observed to present persistent symptoms constituting what has been called "post-acute COVID-19 syndrome" (PACS) or "long COVID-19". Some clinical risk factors have been identified to be associated with PACS development; however, specific mechanisms responsible for PACS pathology remain unknown. This study investigates clinical, immunological, and metabolomic risk factors associated with post-acute COVID-19 syndrome (PACS) in 51 patients, assessed 7-19 months after acute infection. Among the participants, 62.7% were male and 37.2% were female, with an average age of 47.8 years. At the follow-up, 37.2% met the criteria for PACS, revealing significant differences in immunological and metabolomic profiles at the time of acute infection. Patients with PACS were characterized by elevated levels of mature low-density granulocytes (LDGs), interleukin-8 (IL-8), pyruvate, pseudouridine, and cystine. Baseline multivariate analysis showed increased pyruvate and decreased alpha tocopherol levels. At follow-up, there was a decrease in absolute B lymphocytes and an increase in non-classical monocytes and 3-hydroxyisovaleric acid levels. These findings suggest that specific immunological and metabolomic markers during acute infection can help identify patients at higher risk of developing persistent PACS.

Development of modular polymeric nanoparticles for drug delivery using amine reactive chemistry.

Curcumin has been explored for its anti-cancer potential, but is severely limited by its hydrophobicity and sensitivity to light and water. In this study, poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were synthesized to encapsulate curcumin via single emulsion method to improve curcumin stability and bioavailability. The PLGA NPs were coated with oligomeric chitosan (COS) and RGD peptide (a peptide consisting of Arg-Gly-Asp) using amine-reactive chemistry (NHS and EDC). Both COS and RGD had been previously shown to accumulate and target many different types of cancer cells. NPs were characterised based on size distribution, zeta potential, and binding efficiency of RGD peptide. They were also evaluated on encapsulation efficiency, and stability, of curcumin within the NPs. OVCAR-3 cancer cells were treated with COS and RGD-coated PLGA NPs loaded with Coumarin-6 dye for fluorescent imaging of cell uptake. They were also treated with curcumin-loaded NPs to determine cytotoxicity and effectiveness of delivery. The NPs exhibited size distribution and zeta potential within expected values, though binding efficiency of RGD was low. Curcumin-loaded NPs showed significant increase in cytotoxicity over free (unencapsulated) curcumin, and void (empty) NPs, suggesting successful delivery of curcumin as an anti-cancer agent; the performance of COS and RGD coated NPs over bare PLGA NPs was inconclusive, however, optimization will be required to improve formulation during the coating steps. This method of NP synthesis serves as proof of concept for a modular solution to the development of various coated polymeric NPs for other drugs or applications.

The anti-inflammatory properties of green tea extract protect against gentamicin-induced kidney injury.

We assessed in vivo the protective effects and underlying antioxidant and anti-inflammatory properties of dry green tee extract (GTE) on glomerular and tubular kidney function and structure in an experimental model of gentamicin (GEN)-induced nephrotoxicity. Wistar rats were divided into four groups and treated daily for 10 days. The control group received distilled water; the GTE group received 20 µg/g body weight (BW) GTE by gavage; the GEN group received 100 mg/g BW GEN intraperitoneally; and the GEN+GTE group received GTE and GEN simultaneously, as described above. At the beginning and end of treatment, the serum creatinine, fractional excretion of sodium and potassium, and plasma heme oxygenase (HO)-1 levels and oxidative stress (OS) were assessed. At the end of the experiment, kidney fragments were collected for histological evaluation and immunohistochemical studies of cyclooxygenase (COX)-2 and nuclear factor (NF)kB. The levels of interleukin (IL)-1b, IL-4, IL-6, IL-10 and monocyte chemotactic protein (MCP)-1 were measured in kidney tissue. The results showed that GTE attenuated significantly kidney structural injury and prevented GEN-induced kidney functional injury (glomerular and tubular function). GTE significantly attenuated the kidney tissue increase of the proinflammatory mediators NF-kB, COX2, IL-1b and MCP-1 and significantly increased the kidney expression of the anti-inflammatory cytokines IL-6 and IL-10. However, GTE did not prevent OS increase in GEN-treated animals. In conclusion, GTE protected against GEN nephrotoxicity, likely due to direct blockade of the inflammatory cascade, which might had occurred independently of its antioxidant effect.

Life Cycle Assessment and Net Energy Analysis of an Integrated Hydrothermal Liquefaction-Anaerobic Digestion of Single and Mixed Beverage Waste and Sewage Sludge.

The conversion of biomass to bioenergy is one of the approaches to creating a sustainable society. In this study, the life cycle assessment and the net energy analysis of converting mixed sewage sludge and beverage waste into bioenergy via a combined hydrothermal liquefaction-anaerobic digestion (HTL-AD) system was carried out. Primary sludge (PS), winery rose lees (RL), brewery Trub (BT), the mixture of brewery trub and primary sludge (BTPS) and the mixture of winery rose lees and primary sludge (RLPS) were the feedstocks considered. Efficient energy utilization [in form of net energy ratio (NER)], and environmental emissions were evaluated. The NER of BT (2.07) and RL (1.76) increased when mixed with PS (3.18) to produce BTPS (3.20) and RLPS (2.85). Also, the HTL phase of the combined HTL-AD system produced a greater NER than the AD phase in BT, BTPS, and PS and vice-versa in RL and RLPS. Six environmental impact categories were studied namely global warming, terrestrial acidification, ionizing radiation, terrestrial ecotoxicity, human carcinogenic toxicity, and human non-carcinogenic toxicity. RL produced the greatest environmental impact while BTPS produced the least impact, thus indicating the advantage of feedstock combination. This study shows that the combination of feedstocks for bioenergy production in an HTL-AD system does not only increase the quality and quantity of products but also increases the overall NER as well as reducting the environmental impacts. The study also proved that an integrated HTL-AD system is an energy efficient system with greater resource utilization and less environmental footprint than the constituent systems.

Primary Hodgkin Lymphoma of the Breast: A Case Report and Literature Review Examining the Use of Different Chemotherapy Regimens.

Primary classic Hodgkin lymphoma (HL) of the breast is a rare type of breast disease. The diagnosis is mostly confirmed by an excisional biopsy. The first line of treatment commonly used for Hodgkin lymphoma is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Our case report is about a 48-year-old lady who was diagnosed with bilateral breast Hodgkin lymphoma following an excisional biopsy and was treated with brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD). The patient responded positively after the initiation of the regimen. There is scarce data on the classic Hodgkin lymphoma of the breast, and even with the wide use of first-line treatment using ABVD, the disease is still difficult to manage. Hence, patients with breast masses should be screened for classic HL of the breast, and larger studies are needed to establish specific treatment guidelines concerning HL of the breast to prevent relapse and other complications.

Targeting MERTK on tumour cells and macrophages: a potential intervention for sporadic and NF2-related meningioma and schwannoma tumours.

Meningioma and schwannoma are common tumours of the nervous system. They occur sporadically or as part of the hereditary NF2-related schwannomatosis syndrome. There is an unmet need for new effective drug treatments for both tumour types. In this paper, we demonstrate overexpression/activation of TAM (TYRO3/AXL/MERTK) receptors (TAMs) and overexpression/release of ligand GAS6 in patient-derived meningioma tumour cells and tissue. For the first time, we reveal the formation of MERTK/TYRO3 heterocomplexes in meningioma and schwannoma tissue. We demonstrate the dependence of AXL and TYRO3 expression on MERTK in both tumour types, as well as interdependency of MERTK and AXL expression in meningioma. We show that MERTK and AXL contribute to increased proliferation and survival of meningioma and schwannoma cells, which we inhibited in vitro using the MERTK/FLT3 inhibitor UNC2025 and the AXL inhibitor BGB324. UNC2025 was effective in both tumour types with superior efficacy over BGB324. Finally, we found that TAMs are expressed by tumour-associated macrophages in meningioma and schwannoma tumours and that UNC2025 strongly depleted macrophages in both tumour types.

Comparison of plasma clearance of [51Cr]CrEDTA based on three, two and single samples to measure the glomerular filtration rate in patients with solid tumors: a prospective cross-sectional analysis.

OBJECTIVES: [51Cr]CrEDTA is used to measure the Glomerular Filtration Rate (GFR) in different clinical conditions. However, there is no consensus on the ideal number of blood samples to be taken and at what time points to measure its clearance. This study aimed to compare Slope Intercept (SI) and Single-Sample (SS) methods for measuring GFR in patients with solid tumors, stratified by age, GFR, and Body Mass Index (BMI). METHODS: 1,174 patients with cancer were enrolled in this prospective study. GFR was calculated by the SI method using blood samples drawn 2-, 4-, and 6-hours after [51Cr]CrEDTA injection (246-GFR). GFR was also measured using the SI method with samples at 2 and 4 hours (24-GFR) and at 4 and 6 hours (46-GFR), and SS methods according to Groth (4Gr-GFR) and Fleming (4Fl-GFR). Statistical analysis was performed to assess the accuracy, precision, and bias of the methods. RESULTS: Mean 246-GFR was 79.2 ± 21.9 mL/min/1.73 m2. ANOVA indicated a significant difference between 4Gr-GFR and the reference 246-GFR. Bias was lower than 5 mL/min/1.73 m2 for all methods, except for SS methods in subgroups BMI > 40 kg/m2; GFR > 105 or < 45. Precision was adequate and accuracy of 30 % was above 98% for all methods, except for SS methods in subgroup GFR < 45. CONCLUSION: 46-GFR and 246-GFR have high agreement and may be used to evaluate kidney function in patients with solid tumors. Single-sample methods can be adopted in specific situations, for non-obese patients with expected normal GFR.

Microbiome Dysbiosis, Dietary Intake and Lifestyle-Associated Factors Involve in Epigenetic Modulations in Colorectal Cancer: A Narrative Review.

Background: Colorectal cancer is the second cause of cancer mortality and the third most commonly diagnosed cancer worldwide. Current data available implicate epigenetic modulations in colorectal cancer development. The health of the large bowel is impacted by gut microbiome dysbiosis, which may lead to colon and rectum cancers. The release of microbial metabolites and toxins by these microbiotas has been shown to activate epigenetic processes leading to colorectal cancer development. Increased consumption of a 'Westernized diet' and certain lifestyle factors such as excessive consumption of alcohol have been associated with colorectal cancer.Purpose: In this review, we seek to examine current knowledge on the involvement of gut microbiota, dietary factors, and alcohol consumption in colorectal cancer development through epigenetic modulations.Methods: A review of several published articles focusing on the mechanism of how changes in the gut microbiome, diet, and excessive alcohol consumption contribute to colorectal cancer development and the potential of using these factors as biomarkers for colorectal cancer diagnosis.Conclusions: This review presents scientific findings that provide a hopeful future for manipulating gut microbiome, diet, and alcohol consumption in colorectal cancer patients' management and care.

Agile scores in MASLD and ALD: External validation and their utility in clinical algorithms.

BACKGROUND & AIMS: Agile scores, including liver stiffness measurements (LSM) and routine clinical/laboratory biomarkers, have been developed for advanced fibrosis (F≥3) and cirrhosis (F4), respectively, in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We independently validated the diagnostic accuracy of these scores in MASLD, alcohol-related liver disease (ALD) and chronic hepatitis B or C (CHB/C) and assessed them in clinical algorithms with FIB-4 and LSM. METHODS: We included 4,243 patients (MASLD: 912, ALD: 386, CHB: 597, CHC: 2,348) with LSM, liver biopsy and laboratory tests within 6 months. FIB-4, Agile 3+ and Agile 4 scores were calculated. RESULTS: For F≥3, the diagnostic accuracy of Agile 3+ and LSM were similar in MASLD (AUC: 0.86 vs. 0.86, p = 0.831) and ALD (0.92 vs. 0.94, p = 0.123). For cirrhosis, Agile 4 was similar to LSM in MASLD (0.89 vs. 0.90, p = 0.412) and ALD (0.94 vs. 0.95, p = 0.513). Agile 3+/4 performed worse than LSM in CHB/C. Using predefined dual thresholds of 90% sensitivity/specificity, correct classification rates in MASLD were 66% vs. 61% using Agile 3+ vs. LS dual cut-offs and 71% vs. 67% in ALD, respectively. When using Agile 3+ or LSM as a second step after FIB-4 >1.3, correct classification rates were higher with Agile 3+ than LSM, both for MASLD (75% vs. 71%) and ALD (76% vs. 72%), with fewer indeterminate results. Positive agreement of LSM and Agile 3+/4 significantly increased the specificity of a diagnosis of advanced fibrosis/cirrhosis. CONCLUSION: Agile 3+ and Agile 4 have equal diagnostic accuracy with LSM in both MASLD and ALD but result in fewer indeterminate results. Sequential use of FIB-4 and Agile 3+/4 or concurrent Agile 3+/4 and LSM can be used to further optimize F≥3 diagnosis. IMPACT AND IMPLICATIONS: As of today, it is accepted that there will be no single non-invasive test or an isolated cut-off for identifying patients with advanced chronic liver disease. Here, we confirmed that Agile 3+ and Agile 4 scores are useful alternatives to simple liver stiffness measurement in diagnosing advanced fibrosis/cirrhosis in steatotic liver disease, but they do not perform as well in chronic viral hepatitis. Agile scores can help optimize the diagnosis of advanced fibrosis/cirrhosis in a dual cut-off strategy by reducing the number of indeterminate results either alone or in a sequential strategy after FIB-4. The combination of Agile scores and liver stiffness measurement can further increase our confidence in a positive diagnosis of advanced fibrosis/cirrhosis. These novel combination strategies can be useful tools to predict the likelihood of advanced stages of liver disease with the highest possible accuracy in a secondary/tertiary healthcare setting.

Long-Term Outcomes of a Percutaneous Wide-Diameter Bone-Anchored Hearing Implant: A Clinical Evaluation of More than 800 Implants.

OBJECTIVE: This study evaluates the clinical outcomes of 807 percutaneous wide-diameter bone-anchored hearing implants (BAHIs) in 701 patients. In addition, it compares patient groups and examines bone conduction device (BCD) usage. STUDY DESIGN: Retrospective cohort study. Mean follow-up period of 3.8 years. SETTING: Tertiary referral center. PATIENTS: All patients implanted with a percutaneous wide-diameter BAHI until December 2020 were included. Patients were divided into age groups, "loading-time" groups, and, if applicable, specific subgroups thought to be at risk for complications postsurgery, e.g., intellectual disability and comorbidities. MAIN OUTCOME MEASURES: Soft tissue reaction, implant survival, revision surgery, and BCD usage. RESULTS: In 9.1% of the 5,188 observations of 807 implants, an adverse soft tissue reaction was reported according to the Holgers' scale. Significantly more (adverse) soft tissue reactions were observed in children and intellectually disabled (ID) patients (p < 0.05). Comorbidity subgroups showed no significant differences in soft tissue reactions. Implant loss percentage, including explantations, was 6.2%. Implant survival was significantly worse in patients with ID (14.1%; p = 0.021). Pediatric age, early loading, or comorbidities did not significantly influence implant survival. At least 592 implants (73.4%) were used for bone conduction hearing, of which 65.4% were used daily. CONCLUSION: Both children and ID patients are more prone to (adverse) soft tissue reactions, ID patients only have a higher risk of implant loss. The rate of implant loss in children seemed to be reduced compared to previous studies and thus more comparable to adults since using wide-diameter implants.

Gaussian processes modeling for the prediction of polymeric nanoparticle formulation design to enhance encapsulation efficiency and therapeutic efficacy.

Conventional drugs have been facing various drug delivery obstacles, including first-pass metabolism for oral medications, drug degradation by cellular enzymes, off-target effects, and cytotoxicity of healthy cells. Nanoparticles (NP) application in drug delivery can compensate for these drawbacks to a great extent. NPs can be fabricated using different materials and structures to achieve desired therapeutic effects. For each type of NP material, its physicochemical properties determine compatibility with specific drugs and other supplemental compositions. The optimized material selection becomes prominent in NP development to improve NP performances. Due to the nature of NP fabrication, the process is long and expensive. To accelerate NP composition optimization, machine learning (ML) techniques are among the most promising methods for efficient data predictions and optimizations.As a proof-of concept, we created Gaussian Process (GP) models to make predictions for drug encapsulation efficiency (EE%) and therapeutic efficacy of 32 poly (lactic-co-glycolic acid) (PLGA) NPs that are formed with materials with different physicochemical properties. Two model drugs, doxorubicin (DOX) and docetaxel (DTX) were loaded separately. The IC50 values for the various NPs formulations were evaluated using the OVCAR3 epithelial ovarian cancer cell line. EE% GP model has the highest prediction accuracy with the lowest normalized root-mean-squared-error (RMSE) of 0.187. The DOX and DTX IC50 GP models have normalized RMSEs of 0.296 and 0.206, respectively, which are higher than that of the EE% GP model.

From Black Stools to Gastrointestinal Stromal Tumor (GIST): A Case Report and Literature Review on This Unsuspected Danger.

This case report presents the clinical details of a 42-year-old female without previous medical issues who presented with upper gastrointestinal bleeding (UGIB) characterized by melanotic stools. Initial examination revealed mild anemia and subsequent endoscopy identified a 4 cm submucosal gastric mass displaying recent bleeding indicators. Subsequent surgical pathology confirmed a high-grade gastrointestinal stromal tumor (GIST) of grade 2 with a heightened risk of recurrence. The significance of this case lies in underscoring the necessity of considering GIST in the differential diagnosis of UGIB, particularly among middle-aged individuals with no identifiable risk factors such as recent or chronic non-steroidal anti-inflammatory drug (NSAID) use, peptic ulcer disease, or alarm symptoms. Early detection and prompt surgical intervention assume paramount importance in enhancing patient outcomes. While complete resection stands as the cornerstone of treatment, adjuvant imatinib therapy is recommended for high-risk patients to mitigate the risk of recurrence.

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis.

BACKGROUND & AIMS: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions. METHODS: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported. RESULTS: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%. CONCLUSIONS: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.

Predictive Value of Transrectal Ultrasonic Doppler and Elastographic Features in Prostate Cancer Detection in Lagos University Teaching Hospital.

Introduction: This study aimed at determining the predictive value (PV) of transrectal ultrasonic Doppler and elastographic features in prostate cancer (PCa) detection among patients in Lagos University Teaching Hospital. Materials and Methods: This prospective study involved patients that underwent evaluation for PCa. Participants had digital rectal examination (DRE), prostate-specific antigen (PSA) assay, and transrectal ultrasound-guided prostate biopsy using colour Doppler (CD) and elastography. All cores were sent for histopathology. Data were analysed using Statistical Package for the Social Sciences Version 22.0. CD and elastography PV in PCa detection and their relationships to the Gleason score (GS) were analysed (P < 0.05). Results: Seventy men (aged between 45 and 87 years) were enrolled. Forty-three (61.4%) patients had PCa with a mean age of 69.37 ± 8.22years. The sensitivity, specificity, positive PV (PPV), negative PV (NPV) and accuracy of CD were 8.50%, 97.44%, 64.10%, 66.42% and 66.31%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of elastography were 84.21%, 94.59%, 88.89%, 92.11% and 91.07%, respectively. Conclusion: There is a significant association between decreased elasticity (elastography) and PCa detection but a weak association between increased vascularity (CD) and PCa detection. A positive correlation exists between extent of prostatic stiffness and GS.

Idiopathic CD4 Lymphocytopenia: A Case Report and Literature Review.

Idiopathic CD4 lymphocytopenia (ICL) is a rare condition where CD4 T cell counts are low, similar to advanced human immunodeficiency virus (HIV) infection but without acquired immunodeficiency syndrome (AIDS)-related symptoms. The cause is unknown, and theories suggest issues with T cell production, survival, migration, or immune system dysregulation. Diagnosis involves ruling out other causes of low CD4 T cells. Treatment is based on managing infections and may include immunomodulatory therapies, but evidence is limited. Clinical presentations vary widely, including infections, autoimmune disorders, and malignancies. This study explores challenges in diagnosing persistent fevers and lymphopenia, the role of medical history in treatment, HIV screening issues, UTI management in recurrent cases, and the importance of follow-up care for unresolved symptoms or abnormal lab results. This study utilized a case study approach, focusing on the detailed presentation, evaluation, and management of the patient. Data were collected from the patient's medical records, including laboratory tests. Relevant literature was reviewed to provide context and support for the discussion of diagnostic challenges and management strategies. This case highlights the importance of considering uncommon presentations of common infections in patients with complex medical histories. It underscores the need for thorough evaluation, including comprehensive medical history, diagnostic testing, and follow-up care, to ensure accurate diagnosis and appropriate management. By sharing this case, we aim to enhance the awareness and understanding of such presentations among healthcare providers, leading to improved patient care and outcomes.

Cost-effectiveness of a pediatric operating room installation in Sub-Saharan Africa.

The unmet need for pediatric surgery imposes enormous health and economic consequences globally, predominantly shouldered by Sub-Saharan Africa (SSA) where children comprise almost half of the population. Lack of knowledge about the economic impact of improving pediatric surgical infrastructure in SSA inhibits the informed allocation of limited resources towards the most cost-effective interventions to bolster global surgery for children. We assessed the cost-effectiveness of installing and running two dedicated pediatric operating rooms (ORs) in a hospital in Nigeria with a pre-existing pediatric surgical service by constructing a decision tree model of pediatric surgical delivery at this facility over a year, comparing scenarios before and after the installation of the ORs, which were funded philanthropically. Health outcomes measured in disability-adjusted life years (DALYs) averted were informed by the hospital's operative registry and prior literature. We adopted an all healthcare payor's perspective including costs incurred by the local healthcare system, the installation (funded by the charity), and patients' families. Costs were annualized and reported in 2021 United States dollars ($). The incremental cost-effectiveness ratios (ICERs) of the annualized OR installation and operation were presented. One-way and probabilistic sensitivity analyses were performed. We found that installing and operating two dedicated pediatric ORs averted 538 DALYs and cost $177,527 annually. The ICER of the ORs' installation and operation was $330 per DALY averted (95% uncertainty interval [UI] 315-336) from the all healthcare payor's perspective. This ICER was well under the cost-effectiveness threshold of the country's half-GDP per capita in 2020 ($1043) and remained cost-effective in one-way and probabilistic sensitivity analyses. Installation of additional dedicated pediatric operating rooms in Nigeria with pre-existing pediatric surgical capacity is therefore very cost-effective, supporting investment in children's global surgical infrastructure as an economically sound intervention.

Glomerular Filtration Rate Estimation Using ß2-Microglobulin and ß-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study.

RATIONALE & OBJECTIVE: ß2-Microglobulin (B2M) and ß-trace protein (BTP) are novel endogenous filtration markers that may improve the accuracy of estimated glomerular filtration rate (eGFR) beyond creatinine and cystatin C (eGFRcr-cys), but they have not been assessed in patients with cancer. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Prospective cohort of 1,200 patients with active solid tumors recruited between April 2015 and September 2017. EXPOSURE: CKD-EPI equations without race combining B2M and/or BTP with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR). OUTCOME: Performance of equations compared with eGFRcr-cys and non-GFR determinants of serum B2M and BTP (SB2M, and SBTP, respectively). Measured GFR (mGFR) was determined using the plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA). ANALYTICAL APPROACH: Bias was defined as the median of the differences between mGFR and eGFR, and 1-P30 was defined as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). Linear regression was used to assess association of clinical and laboratory variables with SB2M, and SBTP after adjustment for mGFR. RESULTS: Mean age and mGFR were 58.8±13.2 SD years and 78.4±21.7 SD mL/min/1.73m2, respectively. Performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys (lesser bias and 1-P30). Performance of 2-marker panel equations was as good as eGFRcr-cys (lesser bias and similar 1-P30). SB2M and SBTP were not strongly influenced by cancer site. LIMITATIONS: Participants may have had better clinical performance status than the general population of patients with solid tumors. CONCLUSIONS: B2M and BTP can improve the accuracy of eGFR and may be useful as confirmatory tests in patients with solid tumors, either by inclusion in a multimarker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine. PLAIN-LANGUAGE SUMMARY: The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys). We studied whether using ß2-microglobulin (B2M) and/or ß-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys. Performance of 2-marker panel equations was as good as eGFRcr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients.

BACKGROUND: Structural disconnectivity was found to precede dementia. Global white matter abnormalities might also be associated with postoperative delirium (POD). METHODS: We recruited older patients (≥65 years) without dementia that were scheduled for major surgery. Diffusion kurtosis imaging metrics were obtained preoperatively, after 3 and 12 months postoperatively. We calculated fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), and free water (FW). A structured and validated delirium assessment was performed twice daily. RESULTS: Of 325 patients, 53 patients developed POD (16.3%). Preoperative global MD (standardized beta 0.27 [95% confidence interval [CI] 0.21-0.32] p < 0.001) was higher in patients with POD. Preoperative global MK (-0.07 [95% CI -0.11 to (-0.04)] p < 0.001) and FA (0.07 [95% CI -0.10 to (-0.04)] p < 0.001) were lower. When correcting for baseline diffusion, postoperative MD was lower after 3 months (0.05 [95% CI -0.08 to (-0.03)] p < 0.001; n = 183) and higher after 12 months (0.28 [95% CI 0.20-0.35] p < 0.001; n = 45) among patients with POD. DISCUSSION: Preoperative structural disconnectivity was associated with POD. POD might lead to white matter depletion 3 and 12 months after surgery.