Objective
Enlarged vestibular aqueduct (EVA) is a congenital condition that can lead to various outcomes in pediatric patients including hearing loss and vestibular dysfunction. Our goal was to ...critically appraise the literature on the proportion of patients with EVA who report vestibular dysfunction, determine relevant risk factors for the development of these symptoms, and describe vestibular tests and interventions used to improve outcomes.
Methods
A systematic review was performed in accordance with the PRISMA guidelines. We queried the EMBASE, Ovid Medline, and Cochrane Library databases for relevant literature. Studies were included if they had n > 10, reported vestibular symptoms or vestibular function testing in patients with EVA, and were published in English. Nonhuman studies, systematic reviews, and review articles were excluded.
Results
Of 808 identified studies, 20 met inclusion criteria. Subjective vestibular symptoms included dizziness, episodic vertigo, and imbalance. Seventeen studies reported subjective vestibular symptoms, ranging from 2% to 71% of patients between studies. Seventeen studies performed some form of vestibular function test, including physical exam maneuvers (Dix‐Hallpike), caloric testing, electronystagmography, and vestibular evoked myogenic potentials. Of those who had vestibular function testing, 7% to 92% had an abnormal result. Two studies identified head trauma as a risk factor. One study successfully treated patients with BPPV using the Epley maneuver, but other vestibular symptoms were not targeted with treatment.
Conclusion
The degree to which vestibular symptoms impact patients with EVA varies significantly. Performing vestibular function testing may help identify asymptomatic patients with vestibular dysfunction. Future studies should target improving treatment of vestibular symptoms in EVA patients. Laryngoscope, 132:873–880, 2022
The application of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the treatment of acute promyelocytic leukemia (APL). More than 80-90% of patients are expected to be ...cured with a combination of ATRA, ATO and/or chemotherapy. In this review, we focus on the remaining obstacles to a cure for all patients with APL. We review the issue of early death and coagulopathy and discuss the particular challenges in the care of patients with high-risk APL and patients with relapsed APL. We also give recommendations and highlight ongoing efforts to improve the persistently high early death rate and the outcomes of high risk and relapsed APL patients.
Purpose of Review
Immune checkpoint therapy has dramatically changed the therapeutic landscape of solid malignancies. Here, we review the scientific rationale and current data evaluating immune ...checkpoint inhibitors in acute myeloid leukemia (AML).
Recent Findings
Immune checkpoint inhibitor monotherapy has shown limited clinical activity in AML. Initial results from early-phase clinical trials suggest that rational combinations of immune checkpoint inhibition with hypomethylating agents (HMAs) are safe and potentially more promising. There are currently no data directly comparing immune checkpoint inhibition to standard therapies. Emerging immune targets more specific for leukemia cells including LILRB4 may improve future therapeutic efficacy.
Summary
The success of immune checkpoint inhibition in AML has been modest to date. However, an improved understanding of the biology and the use of rational combinations has potential to improve rates of durable responses. Multiple clinical trials in AML are currently evaluating the use of immune checkpoints alone and in combination.
Epigenetics refers to the regulation of gene expression mainly by changes in DNA methylation and modifications of histone proteins without altering the actual DNA sequence. While epigenetic ...modifications are essential for normal cell differentiation, several driver mutations in leukemic pathogenesis have been identified in genes that affect epigenetic processes, such as DNA methylation and histone acetylation. Several therapeutic options to target epigenetic alterations in acute myeloid leukemia (AML) have been successfully tested in preclinical studies and various drugs have already been approved for use in clinical practice. Among these already approved therapeutics are hypomethylating agents (azacitidine and decitabine) and isocitrate dehydrogenase inhibitors (ivosidenib, enasidenib). Other agents such as bromodomain-containing epigenetic reader proteins and histone methylation (e.g. DOT1L) inhibitors are currently in advanced clinical testing. As several epigenetic therapies have only limited efficacy when used as single agents, combination therapies that target AML pathogenesis at different levels and exploit synergistic mechanisms are also in clinical trials. Combinations of either epigenetic therapies with conventional chemotherapy, different forms of epigenetic therapies, or epigenetic therapies with immunotherapy are showing promising early results. In this review we summarize the underlying pathophysiology and rationale for epigenetically-based combination therapies, review current preclinical and clinical data and discuss the future directions of epigenetic therapy combinations in AML.
Nasal fracture is one of the most common pediatric fractures, and diagnosis can be made with clinical findings or with radiographic imaging. The objective of this study is to determine the extent of ...x-ray utilization in decision-making regarding closed reduction of pediatric nasal fracture.
This a case-control study of 117 patients ages 0–18 with a diagnosis of nasal fracture seen at University Hospitals Cleveland Medical Center between January 2015 and January 2020. The exposure group had x-ray imaging of the nasal bones, and the control group had no x-ray imaging.
A total of 59 (50.4%) patients had surgical intervention. The odds ratio to compare x-ray utilization to the control group for patients who underwent closed reduction surgery was .3951 (95% CI: 0.1848-0.8448, p-value = .0166).
The statistical analysis suggests that x-ray use is associated with decreased rates of closed reduction surgery. It is likely that while not necessary for the diagnosis of nasal fracture, x-ray serves as an additional data point for diagnosis confirmation, and may reduce the rate of unnecessary surgery for false positive cases of nasal fracture.
Immunosuppressive therapy (IST) is one therapy option for treatment of patients with lower-risk myelodysplastic syndromes (MDS). However, the use of several different immunosuppressive regimens, the ...lack of high-quality studies, and the absence of validated predictive biomarkers pose important challenges. We conducted a systematic review and meta-analysis according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and searched MEDLINE
PubMed, Ovid EMBASE, COCHRANE registry of clinical trials (CENTRAL), and the Web of Science without language restriction from inception through September 2018, as well as relevant conference proceedings and abstracts, for prospective cohort studies or clinical trials investigating IST in MDS. Fixed and Random-effects models were used to pool response rates. We identified nine prospective cohort studies and 13 clinical trials with a total of 570 patients. Overall response rate was 42.5% 95% confidence interval (CI): 36.1-49.2% including a complete remission rate of 12.5% (95%CI: 9.3-16.6%) and red blood cell transfusion independence rate of 33.4% (95% CI: 25.1-42.9%). The most commonly used forms of IST were anti-thymocyte globulin alone or in combination with cyclosporin A with a trend towards higher response rates with combination therapy. Progression rate to acute myeloid leukemia was 8.6% per patient year (95%CI: 3.3-13.9%). Overall survival and adverse events were only inconsistently reported. We were unable to validate any biomarkers predictive of a therapeutic response to IST. IST for treatment of lower-risk MDS patients can be successful to alleviate transfusion burden and associated sequelae.
Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a systematic review and ...meta-analysis and searched MEDLINE and EMBASE via Ovid, Scopus, COCHRANE registry of clinical trials, and Web of Science from inception through 03/2019 for studies of pegylated IFN (peg-IFN) and non-pegylated IFN (non-peg-IFN) in PV and ET patients. Random-effects models were used to pool response rates for the primary outcome of overall response rate (ORR) defined as a composite of complete response, partial response, complete hematologic response (CHR) and partial hematologic response. Peg-IFN and non-peg-IFN were compared by meta-regression analyses. In total, 44 studies with 1359 patients (730 ET, 629 PV) were included. ORR were 80.6% (95% confidence interval: 76.6-84.1%, CHR: 59.0% 51.5%-66.1%) and 76.7% (67.4-84.0%; CHR: 48.5% 37.8-59.4%) for ET and PV patients, respectively. In meta-regression analyses results did not differ significantly for non-peg-IFN vs. peg-IFN. Annualized rates of thromboembolic complications and treatment discontinuation due to adverse events were low at 1.2% and 8.8% for ET and 0.5% and 6.5% for PV patients, respectively. Both peg-IFN and non-peg-IFN can be effective and safe long-term treatments for ET and PV.
Categorization systems for adverse events are not standardized across care settings and specialties and do not always include near miss events (events where there was potential for patient harm, but ...where no actual harm occurred), making it difficult to effectively assess patient safety for quality improvement.
To develop and assess interrater agreement on a classification system for adverse events reporting that incorporates events in both inpatient and outpatient settings across medical and surgical subspecialties including near miss events.
A cross-sectional study in a tertiary care center including 174 patient cases occurring from 2018 to 2020 was carried out. Data were abstracted from a Department of Otorhinolaryngology-Head and Neck Surgery Quality Assurance database. The cases were comprised of near miss and adverse events occurring in adult and pediatric patients in inpatient, outpatient, and emergency department settings. The ratings took place in March and April of 2022.
Four raters (2 attending physicians and 2 senior resident physicians) were recruited to classify these cases according to 3 classification systems: the National Coordinating Council for Medication Error Reporting and Prevention (NCC-MERP), Clavien-Dindo, and our novel Quality Improvement Classification System (QICS).
The primary outcome was overall interrater agreements using Fleiss κ.
Across all 4 raters grading 174 cases, the NCC-MERP, Clavien-Dindo, and QICS received a κ score. Fair-to-moderate interrater reliability was observed between the resident and attending physician groups across the 3 classification systems: NCC-MERP (κ = 0.33; 95% CI, 0.30-0.35), Clavien-Dindo (κ = 0.47; 95% CI, 0.43-0.50), and QICS (κ = 0.42; 95% CI, 0.39-0.44). Strong interrater concordance was observed for complications across all scenarios.
This cross-sectional study found that the new QICS classification scheme was applicable to wide-ranging clinical scenarios with a focus on patient-centered outcomes including near miss events. In addition, QICS allowed for the comparison of patient outcome data in a multitude of settings.
Background
Up to 20% of patients with acute myeloid leukemia (AML) present with hyperleukocytosis, usually defined as a white blood cell (WBC) count greater than 100 × 109/L. Given the high early ...mortality rate, emergent cytoreduction with either leukapheresis, hydroxyurea, or chemotherapy is indicated, but the optimal strategy is unknown.
Study Design and Methods
For this systematic review and meta‐analysis we searched MEDLINE and EMBASE via Ovid, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception through March 2020 for multiarm studies comparing early mortality rates of patients with AML treated with leukapheresis and those who were not. The risk ratio (RR) of early death for patients who received leukapheresis vs patients who did not was estimated using a sum of the log‐ratio of individual study estimates weighted by sample size.
Results
Among 13 two‐arm, retrospective studies with 1743 patients (486 leukapheresis and 1257 nonleukapheresis patients), leukapheresis did not improve the primary outcome of early mortality compared to treatment strategies in which leukapheresis was not used (RR, 0.88; 95% confidence interval CI, 0.69‐1.13; P = .321) without statistically significant heterogeneity between studies (Cochranʼs Q, 18; P = .115; I2, 33.4%). Patients presenting with clinical leukostasis tended to be more likely to undergo leukapheresis (odds ratio, 2.01; 95% CI, 0.99‐4.08; P = .052).
Conclusion
As we did not find evidence of a short‐term mortality benefit and considering the associated complications and logistic burden, our results argue against the routine use of leukapheresis for hyperleukocytosis among patients with AML.
See editorial on page 2161–2163, in this issue
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