Κυριακή 26 Ιουνίου 2022

Severity of hearing loss after platinum chemotherapy in childhood cancer survivors

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Abstract

Background

Hearing loss is a potential side effect from childhood cancer treatment. We described the severity of hearing loss assessed by audiometry in a representative national cohort of childhood cancer survivors (CCS) and identified clinical risk factors.

Procedure

We included all CCS from the Swiss Childhood Cancer Registry who were diagnosed ≤18 age and treated with platinum-based chemotherapy between 1990 and 2014. We extracted audiograms, treatment-related information, and demographic data from medical records. Two reviewers independently assessed the severity of hearing loss at latest follow-up using the Münster Ototoxicity Scale. We used ordered logistic regression to identify clinical risk factors for severity of hearing loss.

Results

We analyzed data from 270 CCS. Median time from cancer diagnosis to last audiogram was 5 years (interquartile range 2.5–8.1 years). We found 53 (20%) CCS with mild, 78 (29%) with moderate, and 75 (28%) with severe hearing loss. Higher severity grades were associated with (a) younger age at cancer diagnosis (odds ratio [OR] 5.4, 95% confidence interval [CI]: 2.5–12.0 for <5 years); (b) treatment in earlier years (OR 4.8, 95% CI: 2.1–11.0 for 1990–1995); (c) higher cumulative cisplatin doses (OR 13.5, 95% CI: 4.7–38.8 for >450 mg/m2); (d) concomitant cranial radiation therapy (CRT) (OR 4.4, 95% CI: 2.5–7.8); and (e) hematopoietic stem cell transplantation (HSCT) (OR 2.7, 95% CI: 1.0–7.2).

Conclusion

Three of four CCS treated with platinum-based chemotherapy experienced some degree of hearing loss. We recommend closely monitoring patient's hearing function if treated at a young age with high cumulative cisplatin doses, and concomitant CRT as part of long-term care.
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Metastatic rhabdomyosarcoma: evidence of the impact of radiotherapy on survival. A retrospective single‐center experience

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Abstract

Background

The prognosis for patients with metastatic rhabdomyosarcoma (RMS) remains largely unsatisfactory despite the adoption of intensive multimodal therapy. To assess the role of different treatments adopted over the years, we retrospectively analyzed a cohort of patients <21 years old with metastatic RMS, treated from 1990 to 2020 at a referral center for pediatric sarcomas.

Methods

Patients were treated using a multimodal approach that included surgery, radiotherapy and chemotherapy (both high-dose chemotherapy and maintenance therapy in some cases). The type of radiotherapy administered was categorized as: radical (to all sites of disease); partial (to at least one, but not all sites of disease); or none. A landmark analysis was used to examine the impact of radiotherapy on survival, i.e. patients who had an event before day 221 were excluded from the analysis.

Results

The series included 80 patients. Event-free survival (EFS) and overall survival (OS) rates at 5 years were 17.3% and 21.3%, respectively. Survival was significantly associated with radiotherapy to metastatic sites, and with the radiotherapy category. In particular, 5-year EFS and OS rates were 70.6% and 76.0% for patients given radical radiotherapy, and 4.8% and 10.7%, respectively, for those given partial radiotherapy or none. Using the Cox multivariable analysis, OS correlated significantly with radiotherapy category.

Conclusions

While confirming the poor overall outcome of patients with metastatic RMS, this study identified radiotherapy – when given to all sites of disease (including metastases) - as the main variable influencing survival.

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Prospective registration of symptoms and times to diagnosis in children and adolescents with central nervous system tumors: A study of the Swedish Childhood Cancer Registry

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Abstract

Background

The elapsed time taken to diagnose tumors of the central nervous system in children and adolescents varies widely. The aim of the present study was to investigate such diagnostic time intervals at a national level in Sweden as they correlate with clinical features.

Methods

Data prospectively accumulated over a 4-year period in the Swedish Childhood Cancer Registry from patients aged 0–18 years were pooled, and diagnostic time intervals were analyzed considering tumor location, tumor type, patient age and sex, initial symptoms, and clinical timelines. All six pediatric oncology centers in Sweden contributed to collection of data. Time points for calculating the total diagnostic interval (TDI) defined as the time from symptom onset to diagnosis were reported in 257 of 319 patients (81%).

Results

The time from symptom onset to the first healthcare consultation, median 2.6 weeks, did not vary significantly between patients categorized according to tumor type or location. The median TDI was 8.3 weeks for the 4-year study period. Patients with optic pathway glioma (TDI 26.6 weeks), those with tumors of the spinal cord (TDI 25.9 weeks), and those with midline tumors (TDI 24.6 weeks) had the longest lead times. Additionally, older age, too few initial symptoms, and seeking initial redress outside an emergency ward were factors associated with a longer time to diagnosis.

Conclusion

This study identified several factors associated with delayed diagnosis of central nervous system tumors among Swedish children and adolescents. These novel data ought to help direct future efforts toward clinical improvement.
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Asphericity of tumor [123I]mIBG uptake as a prognostic factor in high‐risk neuroblastoma

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Abstract

Background

In recent years, many research groups have attempted to identify a subgroup of "ultra-high risk" patients within the high-risk neuroblastoma (NB) category. The aim of our study was to evaluate the prognostic significance of parameters derived from pretherapeutic 123I-meta-iodobenzylguanidine ([123I]mIBG) integrated single photon emission computed tomography and computed tomography in high-risk patients with NB.

Methods

The established parameters metabolic tumor volume (MTV), maximal standardized uptake value (SUVmax) and the novel parameter tumor asphericity as well as clinical (age, stage) and genetic factors (1p/11q deletions and MYCN amplification) were analyzed in this single-center retrospective study of high-risk patients with newly diagnosed NB. Univariate/multivariable Cox regression and propensity score matching were performed for clinical and radiological parameters.

Results

Twenty-eight high-risk patients with NB were included (14 males, median age 28.8 (11.3–41.0), range 3–74 months). Multivariable analysis of "full" cohort identified high asphericity (≥65%, adjusted hazard ratio [HR] 5.32, 95% confidence interval [CI]: 1.18–24.07, p = .03) and MTV (≥50 ml, adjusted HR 4.31, 95% CI: 1.18–15.80, p = .027) as the only factors associated with worse event-free survival. In matched cohort, tumor asphericity was a significant predictor of relapse/progression (HR 3.83, 95% CI: 1.03–14.26, p = .046).

Conclusion

In this exploratory study, imaging parameters related to tumor metabolic activity, tumor asphericity and MTV, provided prognostic value for event-free survival in high-risk NB patients. Asphericity ≥65% and MTV ≥50 ml may serve as additional prognostic factors to those already used.
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Systematic review and meta‐analysis of celiac plexus neurolysis for abdominal pain associated with unresectable pancreatic cancer

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Abstract

Introduction

Celiac plexus neurolysis (CPN) has been developed as adjunctive therapy to medical management (MM) of abdominal pain associated with unresectable pancreatic cancer. We aimed to conduct a systematic review and meta-analysis to obtain updated and more accurate evidence on the efficacy of additional types of CPN, including endoscopic ultrasound-guided CPN (EUS-CPN).

Methods

On March 16, 2021, we performed searches of PubMed, Web of Science, and CENTRAL for original randomized controlled trials (RCTs). We defined the primary outcome as a standardized pain intensity score with a range of 0-10, and evaluated the mean difference between the CPN+MM and MM groups at 4, 8, and 12 weeks after the initiation of treatment. We used a random-effects model to synthesize the mean differences across RCTs.

Results

We selected 10 RCTs involving 646 individuals. The synthesized mean difference in the pain intensity score between the CPN+MM and MM groups was -0.58 (95% confidence interval [CI]: -1.09 to -0.07) (P = 0.034) in favor of CPN+MM at 4 weeks, -0.46 (95%CI: -1.00 to 0.08) (P = 0.081) at 8 weeks, and -1.35 (95%CI: -3.61 to 0.92) (P = 0.17) at 12 weeks.

Conclusions

This updated meta-analysis of CPN demonstrates its efficacy for managing abdominal pain at 4 weeks. Although there are various limitations, when abdominal pain in patients with unresectable pancreatic cancer is poorly controlled with MM alone, CPN should be an option even if the duration of effect is short-lived, taking into account the absence of serious adverse events.
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Increased local concentrations of growth factors from leucocyte‐ and platelet‐rich fibrin do not translate into improved alveolar ridge preservation: an intraindividual mechanistic randomized controlled trial

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Abstract

Aims

Leucocyte- and platelet-rich fibrin (L-PRF) has been tested for enhancing alveolar ridge preservation (ARP), but little is known about the local release profile of growth factors (GF) and the clinical equipoise related to its efficacy remains. This study compared the patterns of GF release, early soft tissue healing and alveolar ridge resorption following unassisted healing and L-PRF application in non-molar extraction sockets.

Materials and Methods

Atraumatic tooth extraction of two hopeless teeth per patient was followed by unassisted healing or L-PRF placement to fill the socket in 18 systemically healthy, nonsmoking subjects. This intraindividual trial was powered to assess changes in horizontal alveolar ridge dimensions 1 mm below the crest of alveolar bone. GF concentrations in wound fluid were assessed with a multiplex assay at 6, 24, 72 and 168 hours. Early healing was evaluated with the wound-healing index and changes in soft tissue volumes on serial digital scans. Hard tissue changes were measured on superimposed CBCT images after 5 months of healing.

Results

L-PRF resulted in higher GF concentrations in WF as compared to the control, but no differences in release patterns or time of peak were observed. No intergroup differences in early healing parameters were observed. Alveolar bone resorption was observed in both groups. No significant intergroup differences were observed in hard tissue healing 1, 3 or 5 mm apical to the original bone crest, or in ability to digitally plan a prosthetically guided implant with or without bone augmentation.

Conclusions

L-PRF increased the GF concentrations in wound fluid of extraction sockets without shifting the pattern observed in unassisted healing, while the increased delivery did not translate into clinical benefits in early wound healing or ARP. The current findings question the assumption that increased local concentrations of GF by L-PRF translate into improved clinical outcomes. Additional definitive studies are needed to establish the benefits of L-PRF in ARP. (clinicaltrials.gov NCT03985033)
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Recovery from chronic periodontal disease is associated with lower risk for incident diabetes

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Abstract

Objective

The presence of periodontal disease (PD) at a single time point has been suggested as a predictor of diabetes risk, but whether changes in PD status are associated with altered risk of diabetes has yet to be reported on a population scale. This study investigated whether recovery from or development of PD in a population is associated with an altered risk for diabetes occurrence.

Methods

Data of subjects who received health screening from 2002 to 2007 were obtained from the National Health Insurance Service - National Health Screening cohort database of Korea. Patients with a history of diabetes were excluded. Changes in PD status were determined from the first two health screenings. Study subjects were divided into 4 groups according to the changes of PD status: PD-free, PD-recovered, PD-developed, and PD-chronic. The outcome was the occurrence of diabetes.

Results

Overall, 111,611 subjects were included for analysis. During a median follow-up of 9.10 years, diabetes developed in 6,102 subjects. The adjusted hazard ratios (HR) for incident diabetes across various PD change groups (in reference to the PD-free group) were: PD-chronic group=1.096 (95% CI 1.026-1.170, P 0.006); PD-developed group=1.073 (95% CI 0.993-1.159, P 0.075); PD-recovered group=1.019 (CI 0.945-1.100, P 0.622). The subjects who recovered from PD had a lower diabetes risk than those who had consistent PD (adjusted HR 0.930, 95% CI 0.865-1.000, P 0.050), whereas those who developed PD had a higher risk for diabetes than those who remained PD-free.

Conclusion

Longitudinal change in PD status is associated with incident diabetes risk. Future intervention studies are necessary to determine if PD treatment can prevent incident diabetes.

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When Effects Cannot be Estimated: Redefining Estimands to Understand the Effects of Naloxone Access Laws

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Violations of the positivity assumption (also called the common support condition) challenge health policy research and can result in significant bias, large variance, and invalid inference. We define positivity in the single- and multiple-timepoint (i.e., longitudinal) health policy evaluation setting, and discuss real-world thr eats to positivity. We show empirical evidence of the practical positivity violations that can result when attempting to estimate the effects of health policies (in this case, Naloxone Access Laws). In such scenarios, an alternative is to estimate the effect of a shift in law enactment (e.g., the effect if enactment had been delayed by some number of years). Such an effect corresponds to what is called a modified treatment policy, and dramatically weakens the required positivity assumption, thereby offering a means to estimate policy effects even in scenarios with serious positivity problems. We apply the approach to define and estimate the longitudinal effects of Naloxone Access Laws on opioid overdose rates. Violations of the positivity assumption (also called the common support condition) challenge health policy research and can result in significant bias, large variance, and invalid inference. We define positivity in the single- and multiple-timepoint (i.e., longitudinal) health policy evaluation setting, and discuss real-world threats to positivity. We show empirical evidence of the practical positivity violations that can result when attempting to estimate the effects of health policies (in this case, Naloxone Access Laws). In such scenarios, an alternative is to estimate the effect of a shift in law enactment (e.g., the effect if enactment had been delayed by some number of years). Such an effect corresponds to what is called a modified treatment policy, and dramatically weakens the required positivity assumption, thereby offering a means to estimate policy effects even in scenarios with serious positivity problems. We apply the approach to define and estimate the longitudinal effec ts of Naloxone Access Laws on opioid overdose rates. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Complications of sinus floor elevation procedure and management strategies: A systematic review

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Abstract

Aim

This systematic review aimed to investigates the types and incidences of complications following sinus floor elevations (SFE) along with their prevention and management strategies.

Materials and methods

Electronic database and hand search were conducted to screen the literature published from January 1960 to June 2021. The selected studies had to report well-described SFE techniques, complications during, and post-SFE. Data extraction included types of SFE techniques, complications, and their treatment strategies.

Results

A total of 74 studies with 4411 SFE procedures met the inclusion criteria. Different SFE techniques demonstrated varying patterns for both complications and complication rates. Postoperative pain, swelling, and edema were widely reported. The most common complications that required intervention following Lateral SFE (LSFE) were sinus membrane perforation (SMP), wound dehiscence, graft exposure and failure, and sinusitis. LSFE had more SMPs and sinusitis cases compared with a transcrestal SFE (TSFE). The presence of benign paroxysmal positional vertigo following TSFE was significant in certain selected studies.

Conclusion

Given the inherent limitations, this systematic review showed distinct features of complications in SFE using varying techniques. Treatment planning for these procedures should incorporate strategies to avoid complication occurrence.
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Effect of body weight on bleeding events of aspirin in ischemic stroke or transient ischemic attack patients

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Effect of body weight on bleeding events of aspirin in ischemic stroke or transient ischemic attack patients

Bodyweight and combination with SSRIs are related to bleeding adverse reaction of aspirin. Patients weighted less than 60 kg will be at a higher risk of adverse bleeding events.


Abstract

What is Known and Objectives

Bleeding is the most common adverse reaction to aspirin and can lead to drug discontinuation or even be life-threatening in the secondary prevention of stroke or transient ischemic attack. The aim of this study was to evaluate risk factors for bleeding adverse reaction of aspirin in ischemic stroke or transient ischemic attack.

Methods

This retrospective analysis included patients treated with aspirin (100 mg) as a secondary prevention for ischemic stroke or transient ischemic attack. The bleeding events that occurred during the first year were collected, including gastrointestinal, skin, nasal cavity, gum, and urinary tract bleeding events. Then, univariate and multivariate logistic regression analyses were used to identify independent factors associated with bleeding events of aspirin.

Results and Discussion

A total of 578 patients were enrolled in this study, and 58 patients developed bleeding during the first year of secondary prevention. Body weight and combination with selective serotonin reuptake inhibitors were found to be significant risk factors for overall bleeding (p = 0.025 and 0.012). Body weight below 60 kg was a risk factor for overall bleeding and gastrointestinal bleeding events.

What is new and conclusion

Patients weighing less than 60 kg were at increased risk of bleeding with 100 mg aspirin for secondary prevention of cerebral infarction transient ischemic attack.
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