Safety and Immunogenicity of a Delayed Heterologous Avian Influenza A(H7N9) Vaccine Boost Following Different Priming Regimens: A Randomized Clinical Trial.

BACKGROUND: Influenza A (H7N9) has caused multiple disease waves with evidence of strain diversification. Optimal influenza A (H7N9) prime-boost vaccine strategies are unknown. METHODS: We recruited participants who had received monovalent inactivated A/Shanghai/2/2013 (H7N9) vaccine (MIV) approximately 5 years earlier, as follows: MIV with MF59 (MF59 × 2 group), MIV with AS03 (AS03 × 2 group), unadjuvanted MIV (No Adj group), MIV with MF59 or AS03 followed by unadjuvanted MIV (Adjx1 group), and A/H7-naive (unprimed group). Participants were randomized to receive 1 dose of AS03-adjuvanted or unadjuvanted A/Hong Kong/125/2017 (H7N9) MIV and were followed for safety and immunogenicity using hemagglutination inhibition (HAI) and neutralizing antibody assays. RESULTS: We enrolled 304 participants: 153 received the adjuvanted boost and 151 received the unadjuvanted boost. At 21 days postvaccination, the proportion of participants with HAI antibody titers against the boosting vaccine strain of ≥40 in the adjuvanted and unadjuvanted arms, respectively, were 88% and 49% in MF59 × 2 group, 89% and 75% in AS03 × 2 group, 59% and 20% in No Adj group, 94% and 55% in Adjx1group, and 9% and 11% in unprimed group. CONCLUSIONS: Serologic responses to a heterologous A(H7N9) MIV boost were highest in participants primed and boosted with adjuvant-containing regimens. CLINICAL TRIALS REGISTRATION: NCT03738241.

Potential diagnostic and prognostic biomarkers of pediatric Burkitt lymphoma identified through miRNA expression profiling.

BACKGROUND: Pediatric Burkitt lymphoma (pBL) is the most common non-Hodgkin lymphoma in children. These patients require prompt diagnosis and initiation of therapy due to rapid tumor growth. The roles of tumor tissue and circulating microRNAs (miRNAs) in the diagnosis or prognostication have not been fully elucidated in pBLs. METHODS: Differentially expressed (DE) miRNAs were identified with microRNA sequencing (miRNA-Seq) in tumor tissues and plasma of diagnostic pBLs. The diagnostic potential of total miRNA concentrations and overexpressed miRNAs were evaluated through receiver operating characteristic (ROC) analyses. Log-rank test was employed to evaluate survival differences associated with DE miRNAs. Selected miRNA expressions were cross-validated with quantitative reverse transcription PCR (qRT-PCR). RESULTS: Total circulating cell-free miRNAs were higher in pBL cases compared to controls. Cancer-associated pathways were enriched among miRNAs differentially expressed in pBL tumor tissues. Several upregulated miRNAs in pBL tumors demonstrated high diagnostic potential. Similarly, ROC analysis of overexpressed plasma miRNAs revealed circulating cell-free or exosomal miRNAs that can distinguish pBLs from control cases. Indeed, integrative analysis of overexpressed circulating exosomal miRNAs showed an enhanced diagnostic potential for certain triple combinations. Kaplan-Meier analyses of DE miRNAs in tumor tissues identified miRNAs predicting overall survival. CONCLUSIONS: Differentially expressed miRNAs in tumor tissue and plasma of pBL have the potential to improve diagnosis and prognosis. IMPACT: Differentially expressed miRNAs in treatment-naive pediatric Burkitt lymphoma cases have diagnostic or prognostic biomarker potential. This is the first study that applied miRNA-Seq on treatment-naive pediatric Burkitt lymphoma cases for identification of differentially expressed miRNAs both in tumor tissue and plasma samples with diagnostic potential. Through systematic analysis of differentially expressed miRNAs, tumor tissue miRNAs associated with the overall survival of pBLs have been discovered. The clinically significant, differentially expressed miRNAs identified in pediatric Burkitt lymphoma cases can potentially improve the current tissue-based or non-invasive clinical practice in terms of diagnosis or prognostication.

Pediatric paravertebral tumors: analysis of 96 patients.

PURPOSE: The most important complication of paravertebral tumors is cord compression (CC), which is an oncologic emergency. Early and appropriate intervention is important in terms of reducing morbidity and mortality. Here, we report our clinical experience with paravertebral tumors. METHODS: The files of patients who were followed up for benign/malignant paravertebral tumors between 1988 and 2022 were evaluated retrospectively. RESULTS: There were 96 patients with paravertebral tumors. The median age at diagnosis was 5 years (1 month-17 years). The male/female ratio was 1.13. The median time to diagnosis was 4 weeks (0-28 weeks). The most common presenting complaint was pain (62.5%). The diagnosis distribution was as follows: sympathetic nervous system (SNS) tumors (n: 38), soft tissue sarcomas (STS) (n: 23), Langerhans cell histiocytosis (LCH) (n: 12), central nervous system (CNS) tumors (n: 9), germ cell tumor (n: 6), lymphomas (n: 4), and benign tumors (n: 4). Sixty-five patients (67.7%) had CC, 40% of whom received chemotherapy as first-line treatment. Decompression surgery was performed in 58.5% of the patients. For patients with CC, 26 patients had advanced disease at admission. Serious neurologic sequelae were observed in seventeen (17.7%) patients. CONCLUSION: Pain and neurological findings in childhood are warning signs for paravertebral tumors and CC. A detailed neurologic examination and radiodiagnostic imaging should be performed, and a definitive diagnosis should be made quickly. Anticancer treatment should be planned multidisciplinary. Decompression surgery should be discussed for patients with severe neurological deficits. Childhood cancers are chemosensitive; if possible, treatment should be initiated with chemotherapy to avoid neurological sequelae.

Model-Informed Clinical Practice - Determining an Appropriate Ampicillin-Sulbactam Redosing Regimen in Surgical Patients by Utilizing Population Pharmacokinetics and Target Attainment Analysis.

In the current study, population pharmacokinetic (PK) of ampicillin-sulbactam was performed based on the clinical pharmacokinetics data collected from a prospective study conducted in 40 surgical patients undergoing prolonged surgery where antibiotic redosing was implemented. A population PK model was successfully developed to characterize the disposition of ampicillin and sulbactam. The final models were two-compartment models for both drugs, with creatinine clearance and heart failure affecting clearance and body surface area having an impact on the central volume of distribution of both ampicillin and sulbactam. Comprehensive Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of 24 different redosing scenarios. Simulation results indicated that the ampicillin-sulbactam 2-h redosing scheme recommended by ASHP guidelines is likely too conservative given that 3-g dose (2-g ampicillin/1-g sulbactam) with 4-h redosing interval can reach the breakpoint of 2 mg/L for ampicillin in all populations even with the aggressive pharmacokinetic/pharmacodynamic (PK/PD) target of 100% fT > MIC. With the target 50% fT > MIC, all redosing schemes evaluated, including the 8-h redosing scenario, are predicted to be able to reach the breakpoint of 64 mg/L in all patients. According to our findings, redosing of ampicillin-sulbactam should be every 4 h instead of the currently recommended 2-h redosing schedule. Our PTA results should inform future updates to existing general antibiotic redosing guidelines; and, when used in combination with the availability of institution- and/or unit-specific ampicillin susceptibility patterns, our PTA results may be used to customize SSI prophylaxis redosing recommendations for ampicillin-sulbactam at individual hospitals.

The association of miR-204 and mir-483 5p expression with clinicopathological features of Wilms tumor: Could this provide foresight?

BACKGROUND: Wilms tumor is the most common cancer of the kidney that occurs during childhood, and histologically, it mimics renal embryogenesis. With the development and improvement of up-to-date treatment protocols, the survival rates of Wilms tumor have increased. However, metastases or local relapses are still observed in 15% of patients. The search for reliable biomarkers to identify at-risk patients is ongoing to predict the variability in treatment success. Currently, the evaluation of clinical, histopathological and genetic features are common diagnostic methods; however, epigenetic features can be examined with microRNA expression analyses and might allow us to comment on the behavior of the tumor and treatment response. METHODS: In this study, we aimed to evaluate the relationship between microRNA-204 and microRNA-483-5p expression with clinicopathological data and the effect on Wilms tumor survival. For this purpose, the expression levels of RNU6B, microRNA-204 and microRNA-483-5p were evaluated in tumor and normal tissue by qreal time-polymerase chain reaction. We also investigated the relationship between microRNA expression levels with the clinicopathological and histological features of Wilms tumor. RESULTS AND CONCLUSION: The results of our study indicate that the relative expression levels of microRNA-204 in Wilms tumor tissues were significantly lower than that in adjacent normal tissues. By contrast, tumor tissue had a higher microRNA-483-5p expression than the corresponding normal tissues. A statistically significant difference between microRNA-204 expression level with age and the presence of anaplasia was observed. The upregulation of microRNA-483-5p was found to have a significant correlation with patients after preoperative chemotherapy and complete tumor necrosis. Taken together, our data suggest that microRNA-204 could play a critical role as a tumor suppressor, whereas microRNA-483-5p acts as an oncogene in Wilms tumor progression. More importantly, microRNA-204 might be a novel predictive biomarker for anaplastic histology and could be useful for developing therapeutic interventions targeting this marker.

Days of Antibiotic Spectrum Coverage: A Novel Metric for Inpatient Antibiotic Consumption.

BACKGROUND: Days of therapy (DOT), the most widely used benchmarking metric for antibiotic consumption, may not fully measure stewardship efforts to promote use of narrow-spectrum agents and may inadvertently discourage the use of combination regimens when single-agent alternatives have greater adverse effects. To overcome the limitations of DOT, we developed a novel metric, days of antibiotic spectrum coverage (DASC), and compared hospital performances using this novel metric with DOT. METHODS: We evaluated 77 antibiotics in 16 categories of antibacterial activity to develop our spectrum scoring system. DASC was then calculated as cumulative daily antibiotic spectrum coverage (ASC) scores. To compare hospital benchmarking using DOT and DASC, we conducted a retrospective cohort study of adult patients admitted to acute care units within the Veterans Health Administration system in 2018. Antibiotic administration data were aggregated to calculate each hospital's DOT and DASC per 1000 days present (DP) for ranking. RESULTS: The ASC score for each antibiotic ranged from 2 to 15. There was little correlation between DOT per 1000 DP and DASC per DOT, indicating that lower antibiotic consumption at a hospital does not necessarily mean more frequent use of narrow-spectrum antibiotics. The differences in each hospital's ranking between DOT and DASC per 1000 DP ranged from -29.0% to 25.0%, respectively, with 27 hospitals (21.8%) having differences >10%. CONCLUSIONS: We propose a novel composite metric for antibiotic stewardship, DASC, that combines consumption and spectrum as a potential replacement for DOT. Further studies are needed to evaluate whether benchmarking using the DASC will improve evaluations of stewardship.

Real-World Impact of the Accelerate PhenoTest BC Kit on Patients With Bloodstream Infections in the Improving Outcomes and Antimicrobial Stewardship Study: A Quasiexperimental Multicenter Study.

BACKGROUND: Bloodstream infections (BSIs) are a leading cause of morbidity and mortality. The Improving Outcomes and Antimicrobial Stewardship study seeks to evaluate the impact of the Accelerate PhenoTest BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs. METHODS: This multicenter, quasiexperimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX, to evaluate the impact this technology has on patients with BSIs. Laboratory and clinical data from hospitalized patients with BSIs (excluding contaminants) were compared between 2 arms, 1 that underwent testing on AXDX (post-AXDX) and 1 that underwent alternative organism identification and susceptibility testing (pre-AXDX). The primary outcomes were time to optimal therapy (TTOT) and 30-day mortality. RESULTS: A total of 854 patients with BSIs (435 pre-AXDX, 419 post-AXDX) were included. Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared with the pre-AXDX arm (40.9 hours; P<.0001). Compared with pre-AXDX, median time to first antimicrobial modification (24.2 vs 13.9 hours; P<.0001) and first antimicrobial deescalation (36.0 vs 27.2 hours; P=.0004) were shorter in the post-AXDX arm. Mortality (8.7% pre-AXDX vs 6.0% post-AXDX), length of stay (7.0 pre-AXDX vs 6.5 days post-AXDX), and adverse drug events were not significantly different between arms. Length of stay was shorter in the post-AXDX arm (5.4 vs 6.4 days; P=.03) among patients with gram-negative bacteremia. CONCLUSIONS: For BSIs, use of AXDX was associated with significant decreases in TTOT, first antimicrobial modification, and time to antimicrobial deescalation.

Evaluation of the Infectious Diseases Society of America's Core Antimicrobial Stewardship Curriculum for Infectious Diseases Fellows.

BACKGROUND: Antimicrobial stewardship (AS) programs are required by Centers for Medicare and Medicaid Services and should ideally have infectious diseases (ID) physician involvement; however, only 50% of ID fellowship programs have formal AS curricula. The Infectious Diseases Society of America (IDSA) formed a workgroup to develop a core AS curriculum for ID fellows. Here we study its impact. METHODS: ID program directors and fellows in 56 fellowship programs were surveyed regarding the content and effectiveness of their AS training before and after implementation of the IDSA curriculum. Fellows' knowledge was assessed using multiple-choice questions. Fellows completing their first year of fellowship were surveyed before curriculum implementation ("pre-curriculum") and compared to first-year fellows who complete the curriculum the following year ("post-curriculum"). RESULTS: Forty-nine (88%) program directors and 105 (67%) fellows completed the pre-curriculum surveys; 35 (64%) program directors and 79 (50%) fellows completed the post-curriculum surveys. Prior to IDSA curriculum implementation, only 51% of programs had a "formal" curriculum. After implementation, satisfaction with AS training increased among program directors (16% to 68%) and fellows (51% to 68%). Fellows' confidence increased in 7/10 AS content areas. Knowledge scores improved from a mean of 4.6 to 5.1 correct answers of 9 questions (P = .028). The major hurdle to curriculum implementation was time, both for formal teaching and for e-learning. CONCLUSIONS: Effective AS training is a critical component of ID fellowship training. The IDSA Core AS Curriculum can enhance AS training, increase fellow confidence, and improve overall satisfaction of fellows and program directors.

White paper on antimicrobial stewardship in solid organ transplant recipients.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a "one-size-fits-all" style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Outpatient and peri-operative antibiotic stewardship in solid organ transplantation.

BACKGROUND: The consequences of inappropriate antimicrobial use including resistance are increasingly recognized as a global public health threat and many steps have been taken over the last few decades to advance antimicrobial stewardship initiatives with most organ transplant centers currently part of institutions with active antimicrobial stewardship programs. METHODS: A review of the literature was conducted and articles were categorized according to the topic and relevance in the judgment of the two authors. RESULTS: A summary review of the currently available literature was created with a focus on periprocedural and outpatient antimicrobial stewardship. Limitations in the data were significant and discussed in the review. CONCLUSION: The principles of antimicrobial stewardship remain important throughout all phases starting with periprocedural prophylactic antimicrobial selection all the way through to discharge and subsequent healthcare encounters. Despite the broad advances in stewardship initiatives and the rapidly progressing supportive data overall there continue to be significant opportunities for additional research within various special patient populations including recipients of solid organ transplantation (SOT). The recent white paper published in the American Journal of Transplantation called to action the transplant and stewardship communities to have an increased focus and awareness of the issues that antimicrobial overuse can present in the SOT patient population. This is an important step that will hopefully generate more data in this group of patients that arguably faces the greatest vulnerability to the consequences of increased antimicrobial resistance.

Gene-Specific DNA Methylation Profiles in Pediatric Medulloblastomas.

INTRODUCTION: Medulloblastoma is the most common pediatric central nervous tumor of high malignancy that has been classified into both histological subtypes and molecular subgroups by the 2016 World Health Organization classification. However, there is a still need to understand the genomic characteristics and predict the clinical course. The aim of the study is to investigate the significance of the methylation profiles in molecular subclassification and precision medicine of the disease. METHODS: The study enrolled 47 pediatric medulloblastoma patients. DNA methylation levels of KLF4, SPINT2, RASSF1A, EZH2, ZIC2, and PTCH1 genes were analyzed using methylation-specific pyrosequencing. The significance of the statistical relationship between methylation profiles and clinicopathological parameters including molecular subgroups and histological subtypes, the status of metastasis, and event-free survival were analyzed. RESULTS: DNA methylation analysis demonstrated that KLF4, PTCH1, and ZIC2 hypermethylation were associated with the SHH-activated subgroup, whereas both SPINT2 and RASSF1A hypermethylation were associated with metastatic disease. EZH2 gene was not methylated in any of the samples. CONCLUSION: We think that customized DNA methylation profiling may be a useful tool in the molecular subclassification of pediatric medulloblastoma and a potential technical approach in precision medicine.

The effect of text message reminders on nausea, vomiting and quality of life in children with cancer receiving cisplatin.

PURPOSE: This study was conducted to examine the effect of text message reminders on nausea, vomiting, and quality of life in children with cancer receiving cisplatin. METHODS: The study was conducted with a pretest-posttest unpaired group model design. The study included 80 children with cancer and their parents (40 controls and 40 experiments) aged between 8 and 18 years, who were on cisplatin treatment, who did not have cognitive disability as a clinical diagnosis, who received chemotherapy during their stay in the clinic, who were literate in Turkish and who volunteered to participate in the study. The educational contents prepared by the researchers to reduce nausea and vomiting were sent to the parents in the experimental group in the form of a text message every day for three weeks. Descriptive statistics, correlation analysis, and regression analysis were used to evaluate the data. RESULTS: While NVTS, ARINVc, ARINVp, Quality of Life Scale pretest and posttest mean scores of both 8-12 and 13-18 age control group children were similar, it was determined that the experimental group's posttest mean scores were higher than the pretest mean scores, and there was a statistically significant difference between the experimental group's pretest and posttest mean scores in terms of the group, time and group*time. In this study, the education program explains 42%, 15%, 16%, 43%, and 43% of the increase in the mean scores of NVTS, ARINVc, ARINVp, Quality of Life Scale Child and Parent Form, respectively, in children aged 8-12. Also, the education program explains 10%, 27%, 28%, 38%, and 39% of the increase in the mean scores of NVTS, ARINVc, ARINVp, Quality of Life Scale Adolescent and Parent Form, respectively, in children aged 13-18. CONCLUSIONS: It has been observed that text message reminders effectively reduce the level of nausea and vomiting and increase the quality of life. PRACTICE IMPLICATIONS: The results of this study, text message reminders can be applied as an alternative intervention method, and including technology-based practices in the care of children with cancer is important in increasing the quality of care.

PD-L1 and PD-L2 Mutations in Pediatric Hodgkin Lymphoma: Do They Have Any Prognostic Significance?

Background: Reed-Sternberg cells can escape from the immune system by enhancement of the expression of PD-L1 and PD-L2. Objectives: The aim of the present study was to investigate the significance PD-L1 and PD-L2 gene mutations in childhood Hodgkin Lymphoma's (HL). Methods: The study included 39 pediatric classical HL cases. PD-L1 and PD-L2 mutations were determined by Sanger sequencing. Clinicopathological parameters were obtained from patients' records. Results: Eight cases (20.5%) showed p.R260C mutations, and three (7.7%) p.R234L in the exome 5 of PD-L1 gene. None of the cases had PD-L2 mutations. p.R260C mutation exhibited a significant relationship with older age and nodular sclerosing (NS) histology and was associated with longer event free survival. Conclusions: Although PD-L1 mutational status did not show statistically significance with well-established prognostic factors, our preliminary data indicate that p.R260C mutation of PD-L1 gene may be associated with longer event free survival in older patients and NS histology in pediatric HL.

The clinical follow-up and management of COVID-19 in children and adolescents with an immunocompromised state or a malignancy.

BACKGROUND: It is still not known how an immunosuppressive state affects the response to coronavirus disease 2019 (COVID-19) in children and adolescents. The aim of this study was to evaluate clinical characteristics, outcomes, and follow-up results of COVID-19 in pediatric patients with a history of immunocompromise or malignancy, retrospectively. METHODS: Patients with a diagnosis of COVID-19 who were under 18 years of age and had a history of immunosuppressive chronic disease or under immunosuppressant treatment were included in the study. Patients were applied to our outpatient clinic or consulted to our department in a tertiary center during the first year of the pandemic. RESULTS: We evaluated 18 patients with a median age of 15.0 (0.6-17.8) years. Twelve patients (66.6%) were tested because of a symptom and the most common symptom was fever (44.4%, n = 8). Ten of the symptomatic patients (55.5% of all cohort) had a mild disease, the remaining two patients (11.1%) with an end-stage malignancy had critical diseases. Twelve patients (66.7%) were managed on an outpatient basis and were followed up at home, while the remaining six (33.3%) required hospitalization. One patient, who had Ewing sarcoma, died during the follow-up in the intensive care unit, and others were recovered without any morbidities. Lymphocyte (LYM) counts were significantly lower, C-reactive protein (CRP), and ferritin levels were higher in the individuals that needed hospitalization (p = 0.039, 0.027, and 0.039, respectively). DISCUSSION: Immunocompromised children and adolescents with COVID-19 should be monitored closely, especially those with an end-stage malignancy, low LYM count, or high CRP and ferritin levels.

Investing in the Future: A Role for Professional Societies to Prepare the Next Generation of Healthcare Leaders Through Curriculum Development and Dissemination.

Professional societies serve many functions that benefit constituents; however, few professional societies have undertaken the development and dissemination of formal, national curricula to train the future workforce while simultaneously addressing significant healthcare needs. The Infectious Diseases Society of America (IDSA) has developed 2 curricula for the specific purpose of training the next generation of clinicians to ensure the future infectious diseases (ID) workforce is optimally trained to lead antimicrobial stewardship programs and equipped to meet the challenges of multidrug resistance, patient safety, and healthcare quality improvement. A core curriculum was developed to provide a foundation in antimicrobial stewardship for all ID fellows, regardless of career path. An advanced curriculum was developed for ID fellows specifically pursuing a career in antimicrobial stewardship. Both curricula will be broadly available in the summer of 2021 through the IDSA website.

Improving outcomes and antibiotic stewardship (IOAS) for patients with Gram-positive bloodstream infections through use of rapid testing: a quasi-experimental multicentre study of the Accelerate PhenoTest™ BC Kit.

BACKGROUND: Data from the Improving Outcomes and Antibiotic Stewardship for Patients with Bloodstream Infections: Accelerate PhenoTest™ BC Kit (AXDX) Registry Study were analysed to determine the impact of rapid organism identification and antimicrobial susceptibility testing (AST) for Gram-positive bacteraemia. PATIENTS AND METHODS: This multicentre, quasi-experimental study evaluated clinical and antimicrobial stewardship metrics following the implementation of AXDX. Data from hospitalized patients with bacteraemia were compared between groups, one that underwent testing on AXDX (post-AXDX) and one that underwent traditional identification and AST (pre-AXDX). An analysis of patients with Gram-positive bacteraemia was performed. The primary outcome was time to optimal therapy (TTOT). Secondary outcomes included time to first antibiotic modification (overall and Gram-positive), duration of unnecessary MRSA coverage, incidence of adverse events, length of stay and mortality. RESULTS: A total of 219 (109 pre-AXDX, 110 post-AXDX) patients with Gram-positive bacteraemia were included. Median TTOT was 36.3 h (IQR, 16.9-56.7) in the pre-AXDX group and 20.4 h (IQR, 7.5-36.7) in the post-AXDX group (P = 0.01). Compared with pre-AXDX, median time to first antibiotic modification (29.1 versus 15.9 h; P = 0.002), time to first Gram-positive antibiotic modification (33.2 versus 17.2 h; P = 0.003) and median duration of unnecessary MRSA coverage (58.4 versus 29.7 h; P = 0.04) were reduced post-AXDX. A trend towards decreased acute kidney injury (24% versus 13%; P = 0.06) was observed in the post-AXDX group. Groups did not differ in other secondary outcomes. CONCLUSIONS: Implementation of AXDX testing for patients with Gram-positive bacteraemia shortened the TTOT and reduced unnecessary antibiotic exposure due to faster antibiotic modifications.

Operational challenges in the COVID-19 era: Asymptomatic infections and vaccination timing.

The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid testing (NAT) for SARS-CoV-2 is unclear, as this result may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of robust outcomes data, transplant professionals at US adult kidney transplant centers were surveyed (February 13, 2021 to April 29, 2021) to determine community practice (N: 92 centers, capturing 41% of centers and 57% of transplants performed). The majority (97%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 32% of centers proceed with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with kidney transplant in patients with positive SARS-CoV-2 NAT results due to presumed viral shedding. Furthermore, few centers are requiring COVID-19 vaccination prior to transplantation at this time.

Evaluation of Risk Factors Causing Ototoxicity in Childhood Cancers Located in the Head and Neck Region Treated With Platinum-based Chemotherapy.

The aim of this study is to evaluate risk factors contributing to the development of ototoxicity in children who received platinum-based chemotherapy for malignancies located in the head and neck region. Eighty-four children who received platinum-based chemotherapy were included. Audiologic evaluations were performed before and after each chemotherapy session through pure tone audiometry, distortion product otoacoustic emissions, and auditory brainstem response tests. Ototoxicity was evaluated using Brock, Muenster, and Chang classifications. Factors such as cranial irradiation, cumulative doses of cisplatin, age, sex, cotreatment with aminoglycosides, schedule of platinum, and type of chemotherapeutic agent were analyzed. Using χ2 tests, all risk factors were matched with the 3 ototoxicity classifications, and multivariate analyses were conducted using statistically significant risk factors. In univariate analyses, being between 5 and 12 years of age, cranial irradiation and being treated with both cisplatin and carboplatin were found to be related to ototoxicity in all 3 classifications. Logistic regression modeling analyses with these 3 risk factors showed that being between 5 and 12 years of age and being treated with both cisplatin and carboplatin significantly increased the risk of ototoxicity.

MRI-based texture analysis for differentiating pediatric craniofacial rhabdomyosarcoma from infantile hemangioma.

OBJECTIVES: To evaluate the diagnostic performance of MRI texture analysis (TA) for differentiation of pediatric craniofacial rhabdomyosarcoma (RMS) from infantile hemangioma (IH). METHODS: This study included 15 patients with RMS and 42 patients with IH who underwent MRI before an invasive procedure. All patients had a solitary lesion. T2-weighted and fat-suppressed contrast-enhanced T1-weighted axial images were used for TA. Two readers delineated the tumor borders for TA independently and evaluated the qualitative MRI characteristics in consensus. The differences of the texture features' values between the groups were assessed and ROC curves were calculated. Logistic regression analysis was used to analyze the value of TA with and without the combination of the qualitative MRI characteristics. A p value < 0.05 was considered statistically significant. RESULTS: Thirty-eight texture features were calculated for each tumor. Eighteen features on T2-weighted images and 25 features on contrast-enhanced T1-weighted images were significantly different between the RMSs and IHs. On contrast-enhanced T1-weighted images, the short-zone emphasis (SZE), which was a gray-level zone length matrix (GLZLM) parameter, had the largest area under the curve: 0.899 (sensitivity 93%, specificity 87%). The independent predictor for the RMS among the qualitative MRI characteristics was heterogeneous contrast enhancement (p < 0.001). Using only a GLZLM_SZE value of lower than 0.72 was found to be the best diagnostic parameter in predicting RMS (p < 0.001; 95% CI, 8.770-992.4). CONCLUSION: MRI-based TA may contribute to differentiate RMS from IH without invasive procedures. KEY POINTS: • Texture analysis may help to distinguish between rhabdomyosarcoma and infantile hemangioma without invasive procedures. • The gray-level zone length matrix parameters, especially the short-zone emphasis, may be a potential predictor for rhabdomyosarcoma. • Using contrast-enhanced T1-weighted images may be superior to T2-weighted images to differentiate rhabdomyosarcoma from infantile hemangioma in texture analysis.

Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study.

Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS), and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of Taenia solium and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety, and tolerability of oxfendazole were evaluated in healthy volunteers in this phase 1 first-in-human (FIH) study. Seventy subjects were randomly assigned to receive a single oral dose of oxfendazole (0.5, 1, 3, 7.5, 15, 30, or 60 mg oxfendazole/kg body weight) or placebo and were followed for 14 days. Blood and urine samples were collected, and the concentrations of oxfendazole were measured using a validated ultraperformance liquid chromatography mass spectrometry method. The pharmacokinetic parameters of oxfendazole were estimated using noncompartmental analysis. Oxfendazole was rapidly absorbed with a mean plasma half-life ranging from 8.5 to 11 h. The renal excretion of oxfendazole was minimal. Oxfendazole exhibited significant nonlinear pharmacokinetics with less than dose-proportional increases in exposure after single oral doses of 0.5 mg/kg to 60 mg/kg. This nonlinearity of oxfendazole is likely due to the dose-dependent decrease in bioavailability that is caused by its low solubility. Oxfendazole was found to be well tolerated in this study at different escalating doses without any serious adverse events (AEs) or deaths. There were no significant differences in the distributions of hematology, biochemistry, or urine parameters between oxfendazole and placebo recipients. (This study has been registered at ClinicalTrials.gov under identifier NCT02234570.).