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1.
Appl Immunohistochem Mol Morphol ; 30(5): 358-365, 2022.
Article in English | MEDLINE | ID: mdl-35293362

ABSTRACT

Classic Hodgkin lymphoma (cHL) is one of the most common pediatric solid tumors and is responsible for cancer-related deaths in children. Therefore, to modulate the active antitumor T-cell immune response in cHL can be a treatment strategy. In the present study, we aimed to investigate the expression profiles of selected antitumor immune response genes in pediatric cHL and their relationships with clinical and prognostic parameters to determine their significance in precision medicine. Thirty-nine pediatric nodal cHL patients were enrolled in the study. We analyzed mRNA expression of selected immune response regulatory genes such as PD-L1, CSF2, CTLA4, CXCL5, IDO1, CXCL8, MIF, NOS2, PDCD1, PTGS2, and TGFß1 using real-time quantitative polymerase chain reaction. Only PD-L1 overexpression was statistically related to bulky disease, advanced tumor stage, and high-risk disease category and seen significantly in Epstein-Barr virus-negative pediatric cHL. No expression profiles were correlated with relapse or survival. We conclude that PD-L1 overexpression in pediatric cHL cases is a strong predictor of high-risk categorization. In addition to being a prognostic biomarker, PD-L1 blockade is also a druggable marker for the targeted therapy in Epstein-Barr virus-negative pediatric Hodgkin lymphoma.


Subject(s)
Epstein-Barr Virus Infections , Hodgkin Disease , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Child , Herpesvirus 4, Human/metabolism , Hodgkin Disease/genetics , Humans , Immunity , Neoplasm Recurrence, Local
2.
J Pediatr Nurs ; 64: e109-e118, 2022.
Article in English | MEDLINE | ID: mdl-34955361

ABSTRACT

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.


Subject(s)
Neoplasms , Text Messaging , Adolescent , Child , Cisplatin/adverse effects , Humans , Nausea/chemically induced , Nausea/drug therapy , Neoplasms/drug therapy , Quality of Life , Vomiting/chemically induced , Vomiting/drug therapy
3.
Clin Infect Dis ; 75(4): 567-576, 2022 Sep 10.
Article in English | MEDLINE | ID: mdl-34910130

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents , Antimicrobial Stewardship , Adult , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Drug Utilization , Humans , Inpatients , Retrospective Studies
4.
Clin Infect Dis ; 2021 Oct 27.
Article in English | MEDLINE | ID: mdl-34718456

ABSTRACT

BACKGROUND: Bloodstream infections (BSI) are a leading cause of morbidity and mortality in hospitalized patients. The IOAS (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, quasi-experimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX testing, to evaluate the impact this technology has on patients with BSI. Laboratory and clinical data from hospitalized patients with BSI (excluding contaminants) were compared between two arms, one that underwent testing on AXDX (post-AXDX) and one that underwent alternative organism identification and susceptibility testing (pre-AXDX). The primary outcomes were time to optimal therapy (TTOT) within 96 hours of blood culture positivity and 30-day mortality. RESULTS: A total of 854 patients with BSI (435 pre-AXDX, 419 post-AXDX) were included. Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared to the pre-AXDX arm (40.9 hours; P<0.0001). Compared with pre-AXDX, median time to first antimicrobial modification (24.2 versus 13.9 hours; P<0.0001) and first antimicrobial de-escalation (36.0 versus 27.2 hours; P=0.0004) were shorter in the post-AXDX arm. Mortality (8.7% pre-AXDX versus 6.0% post-AXDX), length of stay (7.0 pre-AXDX versus 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 versus 6.4 days; P=0.03) 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 de-escalation.

5.
Lancet Respir Med ; 9(12): 1365-1376, 2021 12.
Article in English | MEDLINE | ID: mdl-34672949

ABSTRACT

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19 , Interferon beta-1a/therapeutic use , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/therapeutic use , COVID-19/drug therapy , Double-Blind Method , Female , Humans , Japan , Male , Mexico , Middle Aged , Oxygen , Oxygen Saturation , Republic of Korea , SARS-CoV-2 , Singapore , Treatment Outcome , United States
6.
Turk Patoloji Derg ; 38(2): 99-105, 2022.
Article in English | MEDLINE | ID: mdl-34558657

ABSTRACT

OBJECTIVE: Neuroblastoma (NB) is the most common extracranial solid tumor in children and is responsible for 12% of cancer-related deaths. The status of metastatic disease in the bone marrow (BM) is a predictor of poor outcome. The purpose of this study was to investigate the predictive significance of histopathological examination of BM in NB. MATERIAL AND METHOD: The study included 61 cases with archival bone marrow biopsy tissues. The cases were evaluated regarding the percentage of metastatic tissue and its differentiation. Primary tumor slides were also reviewed to perform the Shimada classification based on the differentiation status and mitosis-karyorrhexis index. The patients' age, gender, NMYC amplification, clinical risk group, and disease outcome were also noted. RESULTS: Of the 61 cases, 17 had BM involvement. Of those, eight cases (47.1%) were refractory NB showing disease relapse. Based on BM examination, five cases (29.4%) were categorized as complete response, seven (41.2%) as progressive disease, three (17.6%) as minimal disease, and two (11.8%) as stable disease. The progressive disease category was significantly related with refractory disease and NMYC amplification along with the high-risk category (p =0.002 and p= 0.003 respectively). Undifferentiated histology and presence of more than 20% of tumor tissue in the BM biopsy at diagnosis were significantly associated with the progressive disease category (p=0.01 and p < 0.001, respectively). CONCLUSION: We conclude that evaluating the percentage of metastatic tumor tissue and tumor differentiation in BM biopsies is of clinical importance in the management of neuroblastoma patients.


Subject(s)
Bone Marrow Diseases , Neuroblastoma , Bone Marrow/pathology , Bone Marrow Diseases/pathology , Child , Humans , Infant , Neuroblastoma/diagnosis , Prognosis
7.
Pediatr Dev Pathol ; 25(2): 82-90, 2022.
Article in English | MEDLINE | ID: mdl-34554028

ABSTRACT

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.


Subject(s)
Cerebellar Neoplasms , DNA Methylation , Medulloblastoma , Cerebellar Neoplasms/genetics , Cerebellar Neoplasms/pathology , Child , Genomics , Humans , Medulloblastoma/diagnosis , Medulloblastoma/genetics
8.
Clin Transplant ; 35(11): e14437, 2021 11.
Article in English | MEDLINE | ID: mdl-34297878

ABSTRACT

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.


Subject(s)
COVID-19 , Adult , Asymptomatic Infections , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccination
9.
Am J Transplant ; 22(1): 96-112, 2022 01.
Article in English | MEDLINE | ID: mdl-34212491

ABSTRACT

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.


Subject(s)
Antimicrobial Stewardship , Organ Transplantation , Anti-Bacterial Agents/therapeutic use , Humans , Tissue Donors , Transplant Recipients , United States
10.
Clin Infect Dis ; 74(6): 965-972, 2022 03 23.
Article in English | MEDLINE | ID: mdl-34192322

ABSTRACT

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.


Subject(s)
Antimicrobial Stewardship , Communicable Diseases , Aged , Communicable Diseases/drug therapy , Curriculum , Education, Medical, Graduate , Fellowships and Scholarships , Humans , Medicare , Surveys and Questionnaires , United States
11.
Gastroenterol Clin North Am ; 50(2): 415-430, 2021 06.
Article in English | MEDLINE | ID: mdl-34024449

ABSTRACT

Infectious gastroenteritis is common after transplantation and can lead to increased morbidity and mortality. A wide range of organisms can lead to gastroenteritis in this patient population. Clostridioides difficile, cytomegalovirus, and norovirus are the most common pathogens. Newer diagnostic methods, especially multiplex polymerase chain reaction, have increased the diagnostic yield of infectious etiologies. In this review, we describe the epidemiology and risk factors for common infectious pathogens leading to gastroenteritis.


Subject(s)
Gastroenteritis , Hematopoietic Stem Cell Transplantation , Norovirus , Organ Transplantation , Diarrhea , Gastroenteritis/diagnosis , Gastroenteritis/epidemiology , Gastroenteritis/etiology , Humans , Norovirus/genetics , Organ Transplantation/adverse effects
12.
J Antimicrob Chemother ; 76(9): 2453-2463, 2021 08 12.
Article in English | MEDLINE | ID: mdl-34021752

ABSTRACT

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.


Subject(s)
Antimicrobial Stewardship , Bacteremia , Anti-Bacterial Agents/therapeutic use , Bacteremia/diagnosis , Bacteremia/drug therapy , Humans
13.
J Pediatr Hematol Oncol ; 43(7): e930-e934, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-33885038

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cranial Irradiation/adverse effects , Head and Neck Neoplasms/drug therapy , Ototoxicity/etiology , Adolescent , Carboplatin/administration & dosage , Child , Child, Preschool , Cisplatin/administration & dosage , Female , Follow-Up Studies , Head and Neck Neoplasms/pathology , Humans , Infant , Male , Ototoxicity/pathology , Prognosis , Retrospective Studies , Risk Factors
14.
Clin Infect Dis ; 73(5): 911-918, 2021 09 07.
Article in English | MEDLINE | ID: mdl-33730751

ABSTRACT

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.


Subject(s)
Antimicrobial Stewardship , Communicable Diseases , Curriculum , Delivery of Health Care , Humans , Societies
15.
Turk J Pediatr ; 63(1): 86-94, 2021.
Article in English | MEDLINE | ID: mdl-33686830

ABSTRACT

BACKGROUND: Catheter-related bloodstream infection (CRBSI) is one of the most common complications of central lines. Data concerning the effectiveness and safety of antibiotic lock therapy (ALT), especially in pediatric hematology and oncology patients, have not yet reached sufficient levels of evidence. We aimed to share our center`s experience on ALT in pediatric cancer and to investigate the causes of ALT failure. METHODS: All cases with CRBSI and treated with ALT administiration in children with cancer between January 2015 and May 2019 were reviewed. Patients characteristics, laboratory and clinical findings, treatments, outcome of ALT, recurrences and reinfections were recorded. Patients with successful and unsuccessful ALT outcomes were compared in order to identify the risk factors for ALT failure. RESULTS: Sixteen eligible CRBSI treated with adjunctive ALT were identified. The most common pathogens were coagulase negative staphylococci (8/16, 50%). Treatment failure was observed in 31.2% (5/16). Younger age alone was an independent risk factor for treatment failure (0.9 vs 6.8 years, p = 0.038). Recurrence and reinfection rates were 23.1% and 16.7%. Mild bleeding occured in two cases (12.5%) and occlusion causing catheter removal was seen in one (6.3%). CONCLUSIONS: ALT was found to be a safe modality with a success rate of 68.8% in children with cancer at our center and younger age was an independent risk factor for treatment failure. Future studies with larger sample sizes are needed to determine the factors affecting the ALT outcome, especially in childhood malignancies.


Subject(s)
Bacteremia , Catheter-Related Infections , Catheterization, Central Venous , Neoplasms , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Catheter-Related Infections/drug therapy , Child , Humans , Retrospective Studies , Risk Factors
17.
Transplant Proc ; 52(9): 2693-2697, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32972761

ABSTRACT

Kidney injury is a well-known complication in people with coronavirus disease 2019 (COVID-19). In kidney transplant recipients with COVID-19, presentation with nephrotic syndrome has not been well described. We report on a 49-year-old black female kidney transplant recipient who presented 25 years after transplant with clinical features of nephrotic syndrome following a diagnosis of COVID-19. Histologic examination showed acute tubular injury with unremarkable glomeruli on light microscopy and diffuse foot process effacement of podocytes on electron microscopy, consistent with minimal change-like podocyte injury. Apolipoprotein L1 (APOL1) genetic testing confirmed 2 high-risk APOL1 alleles in the kidney donor. We speculate that COVID-19-induced systemic or local cytokine release could serve as a second hit in the presence of APOL1 risk alleles and mediate a podocytopathy manifesting as nephrotic syndrome. The presented case with minimal change-like disease, occurring in the context of the donor high-risk APOL1 genotype, extends the spectrum of clinical manifestations in COVID-19-associated nephropathy.


Subject(s)
Apolipoprotein L1/genetics , Coronavirus Infections/immunology , Immunocompromised Host , Nephrosis, Lipoid/genetics , Nephrosis, Lipoid/virology , Pneumonia, Viral/immunology , Betacoronavirus , COVID-19 , Female , Humans , Kidney Transplantation , Middle Aged , Pandemics , SARS-CoV-2
18.
Open Forum Infect Dis ; 7(6): ofaa173, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32587875

ABSTRACT

BACKGROUND: The prevalence of infections due to nontuberculous mycobacteria (NTM) is increasing worldwide, yet little is known about the epidemiology and pathophysiology of these ubiquitous environmental organisms. Pulmonary disease due to Mycobacterium avium complex is most prevalent, but many other NTM species can cause disease in virtually any organ system. As NTM becomes an increasingly common cause of morbidity and mortality, more information is needed about the epidemiology of NTM disease. METHODS: We conducted a retrospective chart review of all patients with cultures that grew NTM at a Midwestern tertiary hospital from 1996 to 2017. Information on demographics, medical history, clinical findings, treatment, and outcome was obtained from medical records of all NTM isolates. American Thoracic Society/Infectious Diseases Society of America criteria were used to define pulmonary NTM infections. RESULTS: We identified 1064 NTM isolates, 365 of which met criteria for NTM infection. Pulmonary cases predominated (185 of 365; 50.7%), followed by skin/soft tissue (56 of 365; 15.3%), disseminated (40 of 365; 11%), and lymphatic (28 of 365; 7.7%) disease. Mycobacterium avium complex was the most common species (184 of 365; 50.4%). Individuals aged >50 years were most affected (207 of 365; 56.7%). Common comorbidities included structural lung disease (116 of 365; 31.8%), use of immunosuppressive medications (78 of 365; 21.4%), malignancy (59 of 365; 16.2%), and human immunodeficiency virus (42 of 365; 11.5%). CONCLUSIONS: This large cohort provides information on the demographics, risk factors, and disease course of patients with pulmonary and extrapulmonary NTM infections. Most patients had medical comorbidities that resulted in anatomic, genetic, or immunologic risk factors for NTM infection. Further population-based studies and increased disease surveillance are warranted to further characterize NTM infection prevalence and trends.

19.
Curr Transplant Rep ; 7(1): 1-11, 2020.
Article in English | MEDLINE | ID: mdl-32432022

ABSTRACT

PURPOSE OF REVIEW: Early diagnosis of infections and immediate initiation of appropriate antimicrobials are crucial in the management of patients before and after organ transplantation. We reviewed the most recent literature and guidelines in this field and organized the current recommendations for healthcare professionals caring for critically ill organ transplant recipients. RECENT FINDINGS: The incidence of multidrug-resistant organisms is increasing. Multidrug-resistant Gram-negative bacteria comprise about 14% of organisms. Vancomycin-resistant enterococci bloodstream infections are also on the rise, as 20.5% of nosocomial enterococci are now vancomycin-resistant, changing empiric antibiotic selection. Fluconazole-resistant Candida species comprise up to 46% of cases of candidemia in hospitalized patients. Consequently, new guidelines recommend primary use of echinocandins in patients with candidemia who have moderate-to-severe disease. Finally, the incidence of emergence of ganciclovir-resistant cytomegalovirus infection in patients is 5-12%, requiring early recognition and change to alternative regimens in the case of poor response to therapy. SUMMARY: Bloodstream infections are a major cause of mortality and morbidity in solid organ transplantation. Mortality as high as 24% and 50% have been reported with sepsis and septic shock respectively. As such, bloodstream infections should be diagnosed rapidly and intravenous antibiotics should be started immediately. Appropriate resuscitation should be initiated and the number and/or dose of immunosuppressive drugs should be reduced. Proper source control must also be achieved with radiologic drainage or surgical intervention as appropriate. Initial antibiotic treatment of these patients should cover both Gram-positive organisms, especially in the presence of intravascular catheters, and Gram-negative bacteria. Echinocandins like caspofungin should also be considered especially in critically ill patients, particularly if a patient has been on total parenteral nutrition or broad-spectrum antibiotics.

20.
Fetal Pediatr Pathol ; 41(1): 49-57, 2022 Feb.
Article in English | MEDLINE | ID: mdl-32401663

ABSTRACT

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.


Subject(s)
B7-H1 Antigen , Hodgkin Disease , Programmed Cell Death 1 Ligand 2 Protein/genetics , Aged , B7-H1 Antigen/genetics , Child , Hodgkin Disease/genetics , Humans , Mutation , Prognosis
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