Development and Validation of a Multiclass Model Defining Molecular Archetypes of Kidney Transplant Rejection: A Large Cohort Study of the Banff Human Organ Transplant Gene Expression Panel.

Gene expression profiling from formalin-fixed paraffin-embedded (FFPE) renal allograft biopsies is a promising approach for feasibly providing a molecular diagnosis of rejection. However, large-scale studies evaluating the performance of models using NanoString platform data to define molecular archetypes of rejection are lacking. We tested a diverse retrospective cohort of over 1400 FFPE biopsy specimens, rescored according to Banff 2019 criteria and representing 10 of 11 United Network of Organ Sharing regions, using the Banff Human Organ Transplant panel from NanoString and developed a multiclass model from the gene expression data to assign relative probabilities of 4 molecular archetypes: No Rejection, Antibody-Mediated Rejection, T Cell-Mediated Rejection, and Mixed Rejection. Using Least Absolute Shrinkage and Selection Operator regularized regression with 10-fold cross-validation fitted to 1050 biopsies in the discovery cohort and technically validated on an additional 345 biopsies, our model achieved overall accuracy of 85% in the discovery cohort and 80% in the validation cohort, with ≥75% positive predictive value for each class, except for the Mixed Rejection class in the validation cohort (positive predictive value, 53%). This study represents the technical validation of the first model built from a large and diverse sample of diagnostic FFPE biopsy specimens to define and classify molecular archetypes of histologically defined diagnoses as derived from Banff Human Organ Transplant panel gene expression profiling data.

Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study.

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.

Infection Rates of an Intraoral Versus Extraoral Approach to Mandibular Fracture Repairs are Equal: A Systematic Review and Meta-Analysis.

PURPOSE: This study investigates whether the intraoral approach to mandibular open reduction and internal fixation, through exposure to the oral cavity's microbiome, results in higher infection rates compared to the extraoral approach, thus addressing a critical public health concern, potentially offering an opportunity to reduce health-care costs, and aiming to guide effective clinical practice. METHODS: In this systematic review with meta-analyses, a review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search was conducted using Embase and PubMed for articles published between 1989 and 2023. Inclusion criteria targeted studies on open reduction and internal fixation mandibular fractures comparing intraoral and extraoral approaches and reporting infection rates. Exclusion criteria eliminated non-English articles, case reports, and studies with insufficient approach-specific data. The primary outcome was the postoperative infection rate, with surgical approach as the predictor. Covariates such as age, sex, diabetes, and smoking status were included when reported. Data were analyzed using R software, employing random-effects models due to anticipated heterogeneity (I2 statistics). RESULTS: From 61 studies, 11 provided direct comparisons involving 1,317 patients-937 intraoral and 380 extraoral. Infection rates were 5.9% for intraoral and 10% for extraoral approaches. Pooled relative risk was 0.94 [95% confidence interval, 0.63, 1.39], suggesting no significant risk difference. Prevalence of infections was estimated at 9% for intraoral and 6.1% for extraoral procedures, with significant heterogeneity (I2 = 84% for intraoral and 56% for extraoral). CONCLUSION: Our meta-analysis found no significant difference in infection rates between the two approaches. There is opportunity to expand on reporting complication rates comparing the various approaches to mandibular fixation. Until these data are presented, surgeon preference may dictate the operative approach to expose the mandible for reduction and fixation.

TransportTools: a library for high-throughput analyses of internal voids in biomolecules and ligand transport through them.

SUMMARY: Information regarding pathways through voids in biomolecules and their roles in ligand transport is critical to our understanding of the function of many biomolecules. Recently, the advent of high-throughput molecular dynamics simulations has enabled the study of these pathways, and of rare transport events. However, the scale and intricacy of the data produced requires dedicated tools in order to conduct analyses efficiently and without excessive demand on users. To fill this gap, we developed the TransportTools, which allows the investigation of pathways and their utilization across large, simulated datasets. TransportTools also facilitates the development of custom-made analyses. AVAILABILITY AND IMPLEMENTATION: TransportTools is implemented in Python3 and distributed as pip and conda packages. The source code is available at https://github.com/labbit-eu/transport_tools. Data are available in a repository and can be accessed via a link: https://doi.org/10.5281/zenodo.5642954. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Ion correlation-driven like-charge attraction in multivalent salt solutions.

The electrostatic double layer force is key to determining the stability and self-assembly of charged colloids and many other soft matter systems. Fully understanding the attractive force between two like-charged surfaces remains a great challenge. Here, we apply the modified Gaussian renormalized fluctuation theory to study ion correlation-driven like-charge attraction in multivalent salt solutions. The effects of spatially varying ion correlations on the structure of overlapping double layers and their free energy are self-consistently accounted for. In the presence of multivalent salts, increasing surface charge or counterion valency leads to a short-range attraction. We demonstrate that although both overcharging and like-charge attraction are outcomes of ion correlation, there is no causal relationship between them. Our theory also captures the non-monotonic dependence of like-charge attraction on multivalent salt concentration. The reduction of attraction at high salt concentrations could be a contributing factor toward the reentrant stability of charged colloidal suspensions. Our theoretical predictions are consistent with the observations reported in experiments and simulations.

Are Surgical Approaches Correlated With BREAST-Q Score Improvements After Reduction Mammoplasty? A Systematic Review.

BACKGROUND: Despite the commonly recognized benefits and drawbacks of each surgical technique for reduction mammoplasty, data on the influence of each surgical approach on patient quality of life and satisfaction remains limited. Our study aims to evaluate the association between surgical factors and BREAST-Q scores for reduction mammoplasty patients. METHODS: A literature review through August 6, 2021, was conducted using the PubMed database to select publications that used the BREAST-Q questionnaire to evaluate outcomes after reduction mammoplasty. Studies examining breast reconstruction, breast augmentation, oncoplastic reduction, or breast cancer patients were excluded. The BREAST-Q data were stratified by incision pattern and pedicle type. RESULTS: We identified 14 articles that met selection criteria. Among 1816 patients, the mean age ranged from 15.8 to 55 years, mean body mass index ranged from 22.5 to 32.4 kg/m 2 , and bilateral mean resected weight ranged from 323 to 1845.96 g. Overall complication rate was 19.9%. On average, satisfaction with breasts improved by 52.1 ± 0.9 points ( P < 0.0001), psychosocial well-being improved by 43.0 ± 1.0 points ( P < 0.0001), sexual well-being improved by 38.2 ± 1.2 points ( P < 0.0001), and physical well-being improved by 27.9 ± 0.8 points ( P < 0.0001). No significant correlations were observed when mean difference was modeled against complication rates or prevalence of superomedial pedicle use, inferior pedicle use, Wise pattern incision, or vertical pattern incision. Complication rates were not correlated with preoperative, postoperative, or mean change in BREAST-Q scores. A negative correlation was noted between the prevalence of superomedial pedicle use and postoperative physical well-being (Spearman rank correlation coefficient [SRCC], -0.66742; P < 0.05). The prevalence of Wise pattern incision was negatively correlated with postoperative sexual well-being (SRCC, -0.66233; P < 0.05) and physical well-being (SRCC, -0.69521; P < 0.05). CONCLUSIONS: Although either preoperative or postoperative BREAST-Q scores may be individually influenced by pedicle or incision type, there was no statistically significant effect of surgical approach or complication rates on the average change of these scores, and overall satisfaction and well-being scores improved. This review suggests that any of the main surgical approaches to reduction mammoplasty provide equally substantial improvements in patient-reported satisfaction and quality of life, but more robust comparative studies would strengthen this area of research.

A Systematic Review of the Impact of Patient Factors on BREAST-Q Outcomes After Reduction Mammoplasty.

BACKGROUND: As reduction mammoplasty rises in popularity, it will become increasingly important to understand the patient-reported outcome measurements associated with a successful operation. There has been a growing body of literature on BREAST-Q outcomes for patients undergoing reduction mammoplasty, but meta-analyses of patient factors and BREAST-Q Reduction Module scores are lacking. This study sought to ascertain which patient factors were associated with improvements in BREAST-Q scores compared with preoperative levels. METHODS: A literature review through August 6, 2021, was conducted using the PubMed database to select publications using the BREAST-Q questionnaire to evaluate outcomes after reduction mammoplasty. Studies examining breast reconstruction, breast augmentation, oncoplastic reduction, or breast cancer patients were excluded. BREAST-Q data were stratified by comorbidities, age, body mass index (BMI), complication rate, and resection weight. RESULTS: Among 14 articles and 1816 patients, the mean age ranged from 15.8 to 55 years, mean BMI ranged from 22.5 to 32.4 kg/m2, and bilateral mean resected weight ranged from 323 to 1845.96 g. Overall complication rate was 19.9%. On average, satisfaction with breasts improved by 52.1 ± 0.9 points (P < 0.0001), psychosocial well-being improved by 43.0 ± 1.0 points (P < 0.0001), sexual well-being improved by 38.2 ± 1.2 points (P < 0.0001), and physical well-being improved by 27.9 ± 0.8 points (P < 0.0001). The mean age was positively correlated with preoperative sexual well-being (Spearman rank correlation coefficient [SRCC]: 0.61, P < 0.05). Body mass index was negatively correlated with preoperative physical well-being (SRCC: -0.78, P < 0.01) and positively correlated with postoperative satisfaction with breasts (SRCC: 0.53, P < 0.05). The mean bilateral resected weight was significantly positively correlated with postoperative satisfaction with breasts (SRCC: 0.61, P < 0.05). No significant correlations were observed between complication rate and preoperative, postoperative, or mean change in BREAST-Q scores. CONCLUSIONS: Reduction mammoplasty improves patient satisfaction and quality of life as reflected by the BREAST-Q. Although preoperative or postoperative BREAST-Q scores may be individually influenced by age and BMI, these variables demonstrated no statistically significant effect on the average change between these scores. This literature review suggests that reduction mammoplasty delivers high satisfaction across a diverse range of patient populations, and additional prospective cohort or comparative studies gathering robust data on other patient factors would benefit this area of research.

Natural Plasmodium falciparum Infection Stimulates Human Antibodies to MSP1 Epitopes Identified in Mice Infection Models upon Non-Natural Modified Peptidomimetic Vaccination.

(1) Background: Malaria, a vector-borne infectious disease, is caused by parasites of the Plasmodium genus, responsible for increased extreme morbidity and mortality rates. Despite advances in approved vaccines, full protection has not yet been achieved upon vaccination, thus the development of more potent and safe immuno-stimulating agents for malaria prevention is a goal to be urgently accomplished. We have focused our research on a strategy to identify Plasmodium spp. epitopes by naturally acquired human antibodies and rodent malaria infection models immunized with site-directed non-natural antigens. (2) Methods: Some predictive algorithms and bioinformatics tools resembling different biological environments, such as phagosome-lysosome proteolytic degradation, affinity, and the high frequency of malaria-resistant and -sensitive HLA-II alleles were regarded for the proper selection of epitopes and potential testing. Each epitope's binding profile to both host cells and HLA-II molecules was considered for such initial screening. (3) Results: Once selected, we define each epitope-peptide to be synthesized in terms of size and hydrophobicity, and introduced peptide-bond surrogates and non-natural amino acids in a site-directed fashion, and then they were produced by solid-phase peptide synthesis. Molecules were then tested by their antigenic and immunogenic properties compared to human sera from Colombian malaria-endemic areas. The antigenicity and protective capacity of each epitope-peptide in a rodent infection model were examined. The ability of vaccinated mice after being challenged with P. berghei ANKA and P. yoelii 17XL to control malaria led to the determination of an immune stimulation involving Th1 and Th1/Th2 mechanisms. In silico molecular dynamics and modeling provided some interactions insights, leading to possible explanations for protection due to immunization. (4) Conclusions: We have found evidence for proposing MSP1-modified epitopes to be considered as neutralizing antibody stimulators that are useful as probes for the detection of Plasmodium parasites, as well as for sub-unit components of a site-directed designed malaria vaccine candidate.

Self-Consistent Description of Vapor-Liquid Interface in Ionic Fluids.

Inhomogeneity of ion correlation widely exists in many physicochemical, soft matter, and biological systems. Here, we apply the modified Gaussian renormalized fluctuation theory to study the classic example of the vapor-liquid interface of ionic fluids. The ion correlation is decomposed into a short-range contribution associated with the local electrostatic environment and a long-range contribution accounting for the spatially varying ionic strength and dielectric permittivity. For symmetric salt, both the coexistence curve and the interfacial tension predicted by our theory are in quantitative agreement with simulation data reported in the literature. Furthermore, we provide the first theoretical prediction of interfacial structure for asymmetric salt, highlighting the importance of capturing local charge separation.

Myocardial Dysfunction in Patients with Cancer.

Myocardial dysfunction in patients with cancer is a major cause of morbidity and mortality. Cancer therapy-related cardiotoxicities are an important contributor to the development of cardiomyopathy in this patient population. Furthermore, cardiac AL amyloidosis, cardiac malignancies/metastases, accelerated atherosclerosis, stress cardiomyopathy, systemic and pulmonary hypertension are also linked to the development of myocardial dysfunction. Herein, we summarize current knowledge on the mechanisms of myocardial dysfunction in the setting of cancer and cancer-related therapies. Additionally, we briefly outline key recommendations on the surveillance and management of cancer therapy-related myocardial dysfunction based on the consensus of experts in the field of cardio-oncology.

Adverse clinical outcomes in patients undergoing both PCI and TAVR: Analysis from a pooled multi-center registry.

BACKGROUND: There is a paucity of data regarding the optimum timing of PCI in relation to TAVR. OBJECTIVE: We compared the major adverse cardiovascular and cerebrovascular events (MACCE) rates among patients who underwent percutaneous coronary intervention (PCI) before transcatheter aortic valve replacement (TAVR) with those who received PCI with/after TAVR. METHODS: In this multicenter study, we pooled all consecutive patients who underwent TAVR at three high volume centers. RESULTS: Among 3,982 patients who underwent TAVR, 327 (8%) patients underwent PCI within 1 year before TAVR, 38 (1%) had PCI the same day as TAVR and 15 (0.5%) had PCI within 2 months after TAVR. Overall, among patients who received both PCI and TAVR (n = 380), history of previous CABG (HR:0.501; p = .001), higher BMI at TAVR (HR:0.970; p = .038), and statin therapy after TAVR (HR:0.660, p = .037) were independently associated with lower MACCE while warfarin therapy after TAVR was associated with a higher risk of MACCE (HR:1.779, p = .017). Patients who received PCI within 1 year before TAVR had similar baseline demographics, STS scores, clinical risk factors when compared to patients receiving PCI with/after TAVR. Both groups were similar in PCI (Syntax Score, ACC/AHA lesion class) and TAVR (valve types, access) related variables. There were no significant differences in terms of MACCE (log rank p = .550), all-cause mortality (log rank p = .433), strokes (log rank p = .153), and repeat PCI (log rank p = .054) in patients who underwent PCI with/after TAVR when compared to patients who received PCI before TAVR. CONCLUSION: Among patients who underwent both PCI and TAVR, history of CABG, higher BMI, and statin therapy had lower, while those discharged on warfarin, had higher adverse event rates. Adverse events rates were similar regardless of timing of PCI.

Treatment of Multiple Myeloma With Daratumumab in a Kidney Transplant Patient.

CLINICAL FEATURES: A middle-aged man with history of kidney transplantation was diagnosed with multiple myeloma (MM); he was treated with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) for induction therapy. However, a repeat bone marrow biopsy after treatment revealed 10% clonal plasma cell involvement. Given residual disease, his treatment regimen was changed to daratumumab, bortezomib, and dexamethasone in an attempt to achieve minimal residual disease. THERAPEUTIC CHALLENGE: Daratumumab was recently approved for treatment of relapsed or refractory MM; there are no data regarding the safety and effectiveness in solid organ transplant patients. SOLUTION: Our patient was treated with a daratumumab-based regimen for MM. His renal function was monitored closely along with donor-specific antibody to assess for risk of graft rejection. His renal function remained stable with minimal proteinuria and negative donor-specific antibody during the treatment course.

Circulating endothelial cells as predictor of long-term mortality and adverse cardiovascular outcomes in hemodialysis patients.

Circulating endothelial cells (CEC) are thought to be markers of endothelial injury. We hypothesized that the numbers of CEC may provide a novel means for predicting long-term survival and cardiovascular events in hemodialysis patients. 54 hemodialysis patients underwent enumeration of their CEC number. We retrospectively analyzed their survival and incidence of adverse cardiovascular events. 22 deaths (41%) were noted over the median follow up period of 3.56 years (IQR 1.43-12) and 6 were attributed to cardiovascular deaths (11%) of which 1 (4%) was in the low CEC (CEC<20 cells/ml) and 5 (19%) in the high CEC (CEC≥20 cells/ml) group. High CEC was associated with worse cardiovascular survival (p = 0.05) and adverse cardiac events (p = 0.01). In multivariate analysis, CEC >20 cells/ml was associated with a 4-fold increased risk of adverse cardiac events (OR, 4.16 [95% CI,1.38-12.54],p = 0.01) while all-cause mortality and cardiovascular mortality were not statistically different. In this hemodialysis population, a single measurement of CEC was a strong predictor of long term future adverse cardiovascular events. We propose that CEC may be a novel biomarker for assessing cardiovascular risk in dialysis patients.

Incidence and risk factors of kidney allograft loss due to BK nephropathy in the pediatric population: A retrospective analysis of the UNOS/OPTN database.

BACKGROUND: BK virus infection can lead to graft dysfunction and loss in kidney transplant recipients. Risk factors for BKV and BKVN have been inadequately studied in children. Here, we evaluate the incidence and risk factors of allograft loss due to BKVN in the pediatric population of the UNOS data set. METHODS: We conducted a retrospective cohort analysis of the UNOS database and identified all pediatric recipients of kidney transplantation between 2000 and 2018. We compared donor and recipient characteristics, including cause of ESRD, among patients who lost their graft due to BKVN or other causes, and those with functioning allograft. Kaplan-Meier curve and Cox regression analysis were performed to evaluate the risk factors. RESULTS: A total of 66 patients (0.47%) suffered graft failure from BKVN. Older age, male gender, HLA mismatch, and rejection at 1 year were significantly associated with BKVN graft failure, compared to recipients with functioning allograft. In comparison with graft loss due to other causes, male gender, higher HLA mismatch, rejection in 1st year and tacrolimus use at discharge were significantly associated with BKVN graft loss. Recipients who received mycophenolate at time of discharge were at reduced risk for BKVN graft failure. Compared to graft failure from other causes, BKVN graft failure had shorter death censored graft survival [P = .001]. ESRD due to urologic causes and Alport syndrome had higher rate of BKVN graft failure. CONCLUSION: Incidence of graft loss from BKVN in the pediatric population was 10.2 per 10 000 patient-years in this study. BKVN is associated with early allograft failure in the pediatric population, compared to other causes of graft loss. Male gender, HLA mismatch, rejection in 1st year, and urological cause of ESRD are risk factors for graft failure from BKVN in children.

Liposomes with pH responsive 'on and off' switches for targeted and intracellular delivery of antibiotics.

pH responsive drug delivery systems are one of the new strategies to address the spread of bacterial resistance to currently used antibiotics. The aim of this study was to formulate liposomes with 'On' and 'Off'' pH responsive switches for infection site targeting. The vancomycin (VCM) loaded liposomes had sizes below 100 nm, at pH 7.4. The QL-liposomes had a negative zeta potential at pH 7.4 that switched to a positive charge at acidic pH. VCM release from the liposome was quicker at pH 6 than pH 7.4. The OA-QL-liposome showed 4-fold lower MIC at pH 7.4 and 8- and 16-fold lower at pH 6.0 against both MSSA and MRSA compared to the bare drug. OA-QL liposome had a 1266.67- and 704.33-fold reduction in the intracellular infection for TPH-1 macrophage and HEK293 cells respectively. In vivo studies showed that the amount of MRSA recovered from mice treated with formulations was 189.67 and 6.33-fold lower than the untreated and bare VCM treated mice respectively. MD simulation of the QL lipid with the phosphatidylcholine membrane (POPC) showed spontaneous binding of the lipid to the bilayer membrane both electrostatic and Van der Waals interactions contributed to the binding. These studies demonstrated that the 'On' and 'Off' pH responsive liposomes enhanced the activity targeted and intracellular delivery VCM.

A Systematic Review of Wellness in Plastic Surgery Training.

BACKGROUND: Physician and resident wellness has been increasingly emphasized as a means of improving patient outcomes and preventing physician burnout. Few studies have been performed with a focus on wellness in plastic surgery training. OBJECTIVES: The aim of this study was to systematically review what literature exists on the topic of wellness in plastic surgery training and critically appraise it. METHODS: A PubMed search was performed to identify journal articles related to wellness in plastic surgery residency. Seventeen studies (6 cohort and 11 cross-sectional) met inclusion criteria and were appraised with the Newcastle-Ottawa Quality Assessment Scale (NOQAS) to determine the quality of the studies based on selection, comparability, and outcome metrics. RESULTS: Critical assessment showed that the studies were highly variable in focus. Overall, the quality of the data was low, with an average NOQAS score of 4.1. Only 2 studies focused on plastic surgery residents, examining work hours and social wellness, respectively; they were awarded NOQAS scores of 3 and 4 out of 10. CONCLUSIONS: The results of this systematic review suggest that little research has been devoted to wellness in surgery training, especially in regard to plastic surgery residents, and what research that has been performed is of relatively low quality. The available research suggests a relatively high prevalence of burnout among plastic surgery residents. Evidence suggests some organization-level interventions to improve trainee wellness. Because outcomes-based data on the effects of such interventions are particularly lacking, further investigation is warranted.

Laparoscopic cholecystectomy in patients with portal cavernoma without portal vein decompression.

INTRODUCTION: Laparoscopic cholecystectomy (LC) in patients with extrahepatic portal vein obstruction causing portal cavernoma (PC) is considered high risk because of portosystemic collateral veins in the hepatocystic triangle. The literature is limited to isolated case reports. We describe our experience of LC in patients with PC. PATIENTS AND METHODS: Data of patients with PC who underwent LC for symptomatic gallstones or related complications was reviewed. Patients with simultaneous cholecystectomy with splenorenal shunt and open cholecystectomy were excluded. Pre-operative evaluation consisted of complete blood count, international normalisation ratio and liver function tests, ultrasound of the abdomen with Doppler, contrast-enhanced computerised tomography, magnetic resonance cholangiopancreatography and esophagogastroscopy as indicated. A standard four-port LC was performed. The technical principles followed were to avoid injury to the collateral veins, liberal use of energy sources and division of dominant collateral veins between clips. RESULTS: Seven adult patients including three females underwent LC. Three patients had thrombosis of previous surgical shunt with persistent PC. The remaining four patients did not have any indication for shunt surgery. Successful LC was performed in six patients. The median duration of surgery was 170 (130-250 min). Blood transfusion was not required. All the patients had uneventful post-operative recovery. The histopathology of gall bladder consists of acute cholecystitis in three patients and chronic cholecystitis in four. CONCLUSION: LC is feasible in patients with PC at a centre with experience in both laparoscopic and portal hypertension surgeries. Excellent outcome with low rate of conversion to open surgery can be achieved.

COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium.

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.

New Insights into Mechanisms of Immune Checkpoint Inhibitor-Induced Cardiovascular Toxicity.

PURPOSE OF REVIEW: The review aims to summarize the present knowledge about cardiovascular toxicities associated with immune checkpoint inhibitors (ICI) and dissect underlying mechanism associated with individual cardiovascular toxicity. RECENT FINDINGS: Widespread use of ICI therapy has allowed for increasing recognition of a wide spectrum of immune-related adverse events that leave all organ systems vulnerable. Immune-mediated cardiovascular toxicities, initially thought to be rare, are more often being reported and present considerable challenges due to their non-specific clinical presentation, potential to have a fulminant progression, and overlap with other cardiovascular and general medical illnesses. Myocarditis is the most common manifestation of ICI-associated cardiovascular toxicity. Pericardial diseases, vasculitis, Takotsubo syndrome, conduction abnormalities, and destabilization of atherosclerotic lesions constitute other significant adverse events. At this stage, mechanisms underlying fundamental biology of cardiac toxicity have not been studied comprehensively and there remain gaps of knowledge in the current literature concerning the underlying pathomechanisms. It is hypothesized that immune-mediated myocarditis is a result of an exaggerated adaptive immune response against shared epitopes in the myocardium and tumor cells. Further, underlying mechanism of other cardiovascular toxicities is still unclear, further compounded by sparsity of epidemiological data. It is paramount to understand the mechanisms behind ICI-induced cardiovascular toxicities to develop appropriate treatment and prevention strategies and minimize the morbidity and mortality of cancer patients undergoing ICI therapy.

A poly(acrylic acid)-modified copper-organic framework for electrochemical determination of vancomycin.

A copper(II) benzene-1,3,5-tricarboxylate (BTC) metal-organic framework (MOF) was modified with poly(acrylic acid) (PAA) and then used in an electrochemical sensor for vancomycin. The MOF, synthesized via a single-pot method, has enhanced solubility and dispersibility in water as compared to HKUST-1 but without compromising its crystallinity and porosity. The MOF was placed on a glassy carbon electrode (GCE) where it shows enhanced electrocatalytic properties. This is assumed to be due to the presence of the poly(acrylic acid) that forms a network between various HKUST-1 crystals through dimer formation between the carboxy groups of BTC and PAA. This also led to better dispersion of the MOF and to improved interaction between MOF and vancomycin. The structural, spectral and electrochemical properties of the MOFs and their vancomycin complexes was characterized. The modified GCE is shown to be a viable tool for electrochemical determination (best at a working potential of 784 mV vs. Ag/AgCl) of the antibiotic vancomycin in spiked urine and serum samples. Response is linear in the 1-500 nM vancomycin concentration range, and the detection limit is 1 nM, with a relative standard deviation of ±4.3%. Graphical abstractSchematic representation of a method for determination of vancomycin. Poly(acrylic acid) modified HKUST-1 (P-HKUST-1) forms a complex with vancomycin [Van-P-HKUST-1] which is coated over glassy carbon electrode (GCE). The decrease in peak current is recorded as response to vancomycin via cyclic voltammetry.