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Neurosurgical Focus Oct 2022Neuropathic pain is undertreated in children. Neurosurgical treatments of pediatric chronic pain are limited by the absence of both US Food and Drug Administration... (Meta-Analysis)
Meta-Analysis
Spinal cord stimulation for treatment of chronic neuropathic pain in adolescent patients: a single-institution series, systematic review, and individual participant data meta-analysis.
OBJECTIVE
Neuropathic pain is undertreated in children. Neurosurgical treatments of pediatric chronic pain are limited by the absence of both US Food and Drug Administration approval and pediatric-specific hardware, as well as weak referral patterns due to a lack of physician education. This study presents a single-institution retrospective case series of spinal cord stimulation (SCS) in children ≤ 19 years of age and a systematic review of SCS in children. The authors' findings may further validate the role of SCS as an effective treatment modality for varied neuropathic pain syndromes found in pediatric patients.
METHODS
The study was a single-center, single-surgeon, retrospective case series of individuals treated between July 2017 and May 2022. The outcomes for pediatric patients with chronic neuropathic pain syndromes indicated by the multidisciplinary pain clinic for evaluation for SCS were cataloged. A systematic review and individual participant data (IPD) meta-analysis was performed for cases treated until May 2022, using PubMed, EMBASE, and Scopus to characterize outcomes of children with neuropathic pain treated with SCS.
RESULTS
Twelve patients were evaluated and 9 were indicated for percutaneous or buried lead trials. Seven female and 2 male patients between the ages of 13 and 19 years were implanted with trial leads. Eight of 9 (89%) patients went on to receive permanent systems. The average trial length was 6 days, and the length of stay for both trial and implant was less than 1 day. Complication rates due to CSF leaks were 22% and 0% for trial and implant, respectively. Visual analog scale pain scores decreased from 9.2 to 2.9 (p = 0.0002) and the number of medications decreased from 4.9 to 2.1 (p = 0.0005). Functional status also improved for each patient. A systematic review identified 13 studies describing pediatric patients with SCS, including 12 providing IPD on 30 patients. In the IPD meta-analysis, pain was reduced in 16/16 (100%) of patients following surgery and in 25/26 (96.2%) at last follow-up. Medication use was decreased in 16/21 (76.2%), and functional outcomes were improved in 29/29 (100%). The complication rate was 5/30 (16.7%).
CONCLUSIONS
SCS effectively decreases pain and medication use for pediatric neuropathic pain syndromes. Patients also report improved functional status, including improved matriculation, gainful employment, and physical activity. There is minimal high-quality literature describing neuromodulation for pain in children. Neuromodulation should be considered earlier as a viable alternative to escalating use of multiple drugs and as a potential mechanism to address tolerance, dependence, and addiction in pediatric patients.
Topics: Adolescent; Adult; Child; Chronic Pain; Female; Humans; Male; Neuralgia; Retrospective Studies; Spinal Cord; Spinal Cord Stimulation; Syndrome; Treatment Outcome; Young Adult
PubMed: 36183181
DOI: 10.3171/2022.7.FOCUS22330 -
European Urology Focus Jan 2023Although the management of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of new systemic agents, still few patients experience a long-term... (Review)
Review
CONTEXT
Although the management of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of new systemic agents, still few patients experience a long-term durable response. Stereotactic ablative radiotherapy (SABR) is nowadays commonly used as metastasis-directed therapy (MDT), but limited data exist on how best to implement this strategy as part of a multimodal approach.
OBJECTIVE
To evaluate the potential role of extracranial SABR in mRCC and to identify future therapeutic developments of SABR in different disease settings.
EVIDENCE ACQUISITION
A systematic review was conducted in May 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement on the PubMed database. Thirty-four studies were selected for inclusion in this systematic review.
EVIDENCE SYNTHESIS
SABR has been used with four main goals: (1) eradication of the whole metastatic burden in synchronous and metachronous oligometastatic patients, resulting in a long-term local control (LC) rate of >90% and median progression-free survival (PFS) ranging between 8 and 15 mo; (2) eradication of oligoprogressive lesions, enabling an extension of the duration of the systemic therapy by approximately 9 mo; (3) improvement of the response to systemic therapy in polymetastatic patients, resulting in an overall response rate ranging from 17% to 56%; and (4) cytoreduction in polymetastatic mRCC patients, with LC rates ranging between 71% and 100%, and preservation of the renal function, but unclear PFS and overall survival impact. Overall, the combination of SABR and systemic agents has been associated with overall good tolerance, with grade ≥3 toxicity ranging from 0% to 13%.
CONCLUSIONS
Current data highlight the role of SABR as an emerging MDT treatment option in both oligometastatic and oligoprogressive extracranial mRCC, able to ensure long-term disease control and delay the use of next-line systemic therapies. The use of SABR for cytoreduction in the de novo metastatic disease and as an immunological booster in the polymetastatic setting remains investigational and warrants further investigations.
PATIENT SUMMARY
Radiotherapy delivered with ablative doses (>6 Gy per fraction) is a promising treatment strategy for patients diagnosed with metastatic renal cell carcinoma. Excellent outcome results have been observed in patients with a limited number of metastases, improving metastasis-free survival by several months. For patients with a few metastases progressing under systemic therapy, radiotherapy allows an extension of the duration of the ongoing therapy by several months.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Progression-Free Survival; Radiosurgery
PubMed: 36151031
DOI: 10.1016/j.euf.2022.08.016 -
Cardiovascular Diabetology Sep 2022People with intermediate hyperglycemia (IH), including impaired fasting glucose and/or impaired glucose tolerance, are at higher risk of developing type 2 diabetes (T2D)...
BACKGROUND
People with intermediate hyperglycemia (IH), including impaired fasting glucose and/or impaired glucose tolerance, are at higher risk of developing type 2 diabetes (T2D) than those with normoglycemia. We aimed to evaluate the performance of published T2D risk prediction models in Chinese people with IH to inform them about the choice of primary diabetes prevention measures.
METHODS
A systematic literature search was conducted to identify Asian-derived T2D risk prediction models, which were eligible if they were built on a prospective cohort of Asian adults without diabetes at baseline and utilized routinely-available variables to predict future risk of T2D. These Asian-derived and five prespecified non-Asian derived T2D risk prediction models were divided into BASIC (clinical variables only) and EXTENDED (plus laboratory variables) versions, with validation performed on them in three prospective Chinese IH cohorts: ACE (n = 3241), Luzhou (n = 1333), and TCLSIH (n = 1702). Model performance was assessed in terms of discrimination (C-statistic) and calibration (Hosmer-Lemeshow test).
RESULTS
Forty-four Asian and five non-Asian studies comprising 21 BASIC and 46 EXTENDED T2D risk prediction models for validation were identified. The majority were at high (n = 43, 87.8%) or unclear (n = 3, 6.1%) risk of bias, while only three studies (6.1%) were scored at low risk of bias. BASIC models showed poor-to-moderate discrimination with C-statistics 0.52-0.60, 0.50-0.59, and 0.50-0.64 in the ACE, Luzhou, and TCLSIH cohorts respectively. EXTENDED models showed poor-to-acceptable discrimination with C-statistics 0.54-0.73, 0.52-0.67, and 0.59-0.78 respectively. Fifteen BASIC and 40 EXTENDED models showed poor calibration (P < 0.05), overpredicting or underestimating the observed diabetes risk. Most recalibrated models showed improved calibration but modestly-to-severely overestimated diabetes risk in the three cohorts. The NAVIGATOR model showed the best discrimination in the three cohorts but had poor calibration (P < 0.05).
CONCLUSIONS
In Chinese people with IH, previously published BASIC models to predict T2D did not exhibit good discrimination or calibration. Several EXTENDED models performed better, but a robust Chinese T2D risk prediction tool in people with IH remains a major unmet need.
Topics: Adult; China; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Prospective Studies; Risk Assessment; Risk Factors
PubMed: 36100925
DOI: 10.1186/s12933-022-01622-5 -
Breast Cancer Research and Treatment Jun 2022Radiation therapy (RT) for triple-negative breast cancer (TNBC) treatment is currently delivered in the adjuvant setting and is under investigation as a booster of... (Review)
Review
PURPOSE
Radiation therapy (RT) for triple-negative breast cancer (TNBC) treatment is currently delivered in the adjuvant setting and is under investigation as a booster of neoadjuvant treatments. However, TNBC radioresistance remains an obstacle, so new biomarkers are needed to select patients for any integration of RT in the TNBC therapy sequence. MicroRNAs (miRs) are important regulators of gene expression, involved in cancer response to ionizing radiation (IR) and assessable by tumor tissue or liquid biopsy. This systematic review aimed to evaluate the relationships between miRs and response to radiation in TNBC, as well as their potential predictive and prognostic values.
METHODS
A thorough review of studies related to miRs and RT in TNBC was performed on PubMed, EMBASE, and Web of Science. We searched for original English articles that involved dysregulation of miRs in response to IR on TNBC-related preclinical and clinical studies. After a rigorous selection, 44 studies were chosen for further analysis.
RESULTS
Thirty-five miRs were identified to be TNBC related, out of which 21 were downregulated, 13 upregulated, and 2 had a double-side expression in this cancer. Expression modulation of many of these miRs is radiosensitizing, among which miR-7, -27a, -34a, -122, and let-7 are most studied, still only in experimental models. The miRs reported as most influencing/reflecting TNBC response to IR are miR-7, -27a, -155, -205, -211, and -221, whereas miR-21, -33a, -139-5p, and -210 are associated with TNBC patient outcome after RT.
CONCLUSION
miRs are emerging biomarkers and radiosensitizers in TNBC, worth further investigation. Dynamic assessment of circulating miRs could improve monitoring and TNBC RT efficacy, which are of particular interest in the neoadjuvant and the high-risk patients' settings.
Topics: Biomarkers; Biomarkers, Tumor; Circulating MicroRNA; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Radiation Tolerance; Triple Negative Breast Neoplasms
PubMed: 35397079
DOI: 10.1007/s10549-022-06533-3 -
The Science of the Total Environment Jun 2022The biphasic hormetic response to stress, defined by low-dose stimulation and high-dose inhibition is frequently observed in insects. Various molecular and biochemical...
The biphasic hormetic response to stress, defined by low-dose stimulation and high-dose inhibition is frequently observed in insects. Various molecular and biochemical responses associated with hormesis in insects have been reported in many studies, but no synthesis of all these findings has been undertaken. We conducted a systematic literature review, analyzing papers demonstrating phenotypic stimulatory effect(s) following exposure to stress where molecular or biochemical response(s) were also examined. Responses observed included stimulation of reproduction, survival and longevity, growth and development, and tolerance to temperature, chemical, or starvation and desiccation, in response to stressors including pesticides, oxidative stress, temperature, crowding and starvation, and radiation. Phenotypic stimulation ranged from <25% increased above controls to >100%. Reproductive stimulation was frequently <25% increased above controls, while stimulated temperature tolerance was frequently >100% increased. Molecular and biochemical responses had obvious direct connections to phenotypic responses in many cases, although not in all instances. Increased expression of heat shock proteins occurred in association with stimulated temperature tolerance, and increased expression of detoxification genes with stimulated pesticide or chemical tolerance, but also stimulated reproduction. Changes in the expression or activity of antioxidants were frequently associated with stimulation of longevity and reproduction. Stress induced changes in vitellogenin and juvenile hormone and genes in the IIS/TOR signalling pathway - which are directly responsible for regulating growth, development, and reproduction - were also reported. Our analysis showed that coordination of expression of genes or proteins associated with protection from oxidative stress and DNA and protein damage is important in the hormetic responses of insects.
Topics: Animals; Antioxidants; Hormesis; Insecta; Oxidative Stress; Reproduction
PubMed: 35218848
DOI: 10.1016/j.scitotenv.2022.154085 -
The Medical Journal of Malaysia Jan 2022Treatment of head and neck cancer patients amidst the COVID-19 pandemic is challenging, whereas prolonged treatment initiation in head and neck squamous cell carcinoma...
INTRODUCTION
Treatment of head and neck cancer patients amidst the COVID-19 pandemic is challenging, whereas prolonged treatment initiation in head and neck squamous cell carcinoma may increase mortality and likelihood of recurrence. Special attention is needed to ensure safe and appropriate care of these patients. This article aims to review and discuss existing research on treatment prioritization and risk stratification of head and neck cancer patients during the pandemic.
MATERIALS AND METHODS
The authors conducted literature search in three databases (PubMed, Cochrane, and Clinical Key) on July 15th, 2020. The keywords were ("Head and Neck Mucosal Malignancy" OR "Head and Neck Cancer") AND ("Management" OR "Head and Neck Surgery") AND ("COVID-19" OR "Pandemic"). The inclusion criteria were cancer in adult patients, published from 2020 in English, and with available access to full text. The exclusion criteria were comments, letters, and case reports. The articles were critically appraised using the Centre of Evidence-based Medicine (CEBM), University of Oxford and Duke University. The literature search strategy is illustrated using Preferred Reporting Items for Systematic review and meta-analysis (PRISMA) flow diagram.
RESULTS
A total of 150 articles were identified; 21 articles were gathered from Clinical Key, 33 from Cochrane, and 96 from Pubmed. After screening abstracts and reviewing the full text, the authors determined five articles met the inclusion criteria. There are several key points of head and neck cancer management in the COVID-19 pandemic. Head and neck cancer management is considered a high-risk procedure; the clinician should use proper personal protective equipment. Before operative treatment, all patients should undergo a PCR test 14 days before surgery. In diagnosing head and neck cancer, laryngoscopy should be considered carefully; and cytology should be preferred instead. Medically Necessary, Time-sensitive (MeNTS) score is recommended for risk stratification and surgery prioritization; it has three domains: procedure, disease, and patient. However, it is not specified to head and neck cancer; therefore, it should be combined with other references. Stanford University Head and Neck Surgery Division Department of Otolaryngology made surgery prioritization into three groups, urgent (should be operated immediately), can be postponed for 30 days, and can be postponed for 30- 90 days. Some urgent cases and should be operated on immediately include cancers involving the airways, decreased renal function, and metastases. For chemoradiation decision to delay or continue should refer to the goal of treatment, current oncologic status, and tolerance to radiation. In terms of patient's follow up, telephone consultation should be maximized.
CONCLUSION
MeNTS scoring combined with Guideline from Department of Otolaryngology at Stanford University prioritizing criteria can be helpful in decision making of stratifying Risk and prioritizing surgery in head and neck cancer management.
Topics: COVID-19; Head and Neck Neoplasms; Humans; Pandemics; Referral and Consultation; Risk Assessment; SARS-CoV-2; Telephone
PubMed: 35086995
DOI: No ID Found -
BioMed Research International 2021The previous lab and clinical studies of the correlation between the ultraviolet B and age-related cataract (ARC) did not reach in the universal agreement, especially in... (Meta-Analysis)
Meta-Analysis
PURPOSE
The previous lab and clinical studies of the correlation between the ultraviolet B and age-related cataract (ARC) did not reach in the universal agreement, especially in different morphological types of ARC. It is important to systemically summarize those previous data of epidemiological studies, which might penetrate the relevance between three morphological types of ARC, cortical, nuclear, and posterior capsular (PSC), with sunlight exposure.
METHODS
PubMed, Web of Science, CNKI, Embase, and Cochrane were searched online. Data were extracted and recalculated, and quality check was performed by hand. Review Manager was used to perform the fixed effects meta-analysis on ARC and its morphological types. The highest exposed dose group was defined as the exposed group, and the lowest dose group as the control group as possible.
RESULTS
Finally, the number of analyzed studies was 31: 20 for ARC and twelve, eleven, and nine for the morphological types cortical, nuclear, and PSC, respectively. The pooled OR for ARC was 1.15 (range 1.00~43.78, 95% CI 1.09 to 1.21). The cortical cataract revealed a slightly higher risk, and pooled OR was 1.03 (range 0.67~2.91, 95% CI 1.02 to 1.03). But the pooled OR for nuclear and PSC were 1.00 (range 0.50~5.35, 95% CI 1.00 to 1.00) and 0.99 (range 0.57~1.87, 95% CI 0.95 to 1.01), respectively.
CONCLUSIONS
The systemic analysis of epidemiological articles reported till now reveals a significantly increased risk of ARC for those exposed with more sunlight, especially the morphological type of cortical cataract.
Topics: Aging; Cataract; Dose-Response Relationship, Radiation; Humans; Risk Factors; Sunlight; Ultraviolet Rays
PubMed: 34805407
DOI: 10.1155/2021/8748463 -
International Journal of Molecular... Jul 2021Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and... (Meta-Analysis)
Meta-Analysis
Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and genotoxicity associated with increased risk of cancer. This review aims to identify the genotoxicity biomarkers that are the most elevated in IR-exposed vs. unexposed health workers. A systematic review of the literature was performed to retrieve relevant studies with various biomarkers of genotoxicity. Subsequent meta-analyses produced a pooled effect size for several endpoints. The search procedure yielded 65 studies. Chromosome aberrations (CA) and micronuclei (MN) frequencies were significantly different between IR-exposed and unexposed workers (θ = 3.19, 95% CI 1.46-4.93; and θ = 1.41, 95% CI 0.97-1.86, for total aberrant cells and MN frequencies, respectively), which was not the case for ring chromosomes and nucleoplasmic bridges. Although less frequently used, stable translocations, sister chromatid exchanges (SCE) and comet assay endpoints were also statistically different between IR-exposed and unexposed workers. This review confirms the relevance of CA and MN as genotoxicity biomarkers that are consistently elevated in IR-exposed vs. unexposed workers. Other endpoints are strong candidates but require further studies to validate their usefulness. The integration of the identified biomarkers in future prospective epidemiological studies is encouraged.
Topics: Biomarkers; Chromosome Aberrations; DNA Damage; Dose-Response Relationship, Radiation; Health Personnel; Humans; Occupational Exposure; Radiation, Ionizing
PubMed: 34299125
DOI: 10.3390/ijms22147504 -
Leukemia Research Sep 2021Non-Hodgkin's lymphoma continues to be a highly prevalent entity in the general population. Currently, there are multiple treatment schemes based on chemotherapeutic... (Review)
Review Meta-Analysis
Non-Hodgkin's lymphoma continues to be a highly prevalent entity in the general population. Currently, there are multiple treatment schemes based on chemotherapeutic agents with a great success rate. However, there is a non-negligible percentage of patients who may relapse or be refractory. In this sense, new therapeutic options have emerged in the search for adequate responses, such as monoclonal antibodies that target the CD20 molecule. Another valid option is radioimmunotherapy (RIT), which combines using monoclonal antibodies for the specific targeting of malignant cells and radiation to destroy these cells. Despite the promising results that favor RIT in several clinical studies in different target populations and types of NHL, one situation to consider is the association of this therapy and second neoplasms (acute myeloid leukemia (AML) or myelodysplastic syndrome (MSD)). In this sense, we have proposed this meta-analysis to analyze the published information and determine the incidence of this association and determine this therapy's safety.
Topics: Humans; Lymphoma, Non-Hodgkin; Radiation Tolerance; Radioimmunotherapy; Treatment Outcome
PubMed: 34052662
DOI: 10.1016/j.leukres.2021.106615 -
BMC Cancer May 2021It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid...
Efficacy and safety of peptide receptor radionuclide therapy in advanced radioiodine-refractory differentiated thyroid cancer and metastatic medullary thyroid cancer: a systematic review.
BACKGROUND
It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC.
METHODS
For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews.
RESULTS
Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported.
CONCLUSION
Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events.
TRIAL REGISTRATION
PROSPERO registration number: CRD42019125245 .
Topics: Carcinoma, Neuroendocrine; Hematologic Diseases; Humans; Iodine Radioisotopes; Octreotide; Organometallic Compounds; Radiation Injuries; Radiation Tolerance; Radiopharmaceuticals; Renal Insufficiency; Thyroid Neoplasms; Treatment Outcome; Yttrium Radioisotopes
PubMed: 34016077
DOI: 10.1186/s12885-021-08257-x