Dear Reviewers and Editors,
亲爱的审稿人和编辑,
I would like to express my sincere gratitude for your meticulous review and valuable comments on our manuscript. I have carefully read each of your review comments and am deeply impressed by your professional expertise and keen insights.
我谨对您对我们稿件的细致审阅和宝贵意见表示诚挚的谢意。我仔细阅读了您的每一条审稿意见,您的专业知识和敏锐的洞察力给我留下了深刻的印象。
Through your comments, I have clearly recognized my oversights in describing study details and conducting statistical analyses. Your constructive feedback has not only helped me re-examine various aspects of the research but also provided invaluable guidance for improving the overall quality of the manuscript.
通过您的评论,我清楚地认识到我在描述研究细节和进行统计分析方面的疏忽。您的建设性反馈不仅帮助我重新审视研究的各个方面,而且为提高稿件的整体质量提供了宝贵的指导。
I have carefully considered each of your suggestions and have revised the manuscript accordingly. Your expert opinions have played a crucial role in enhancing the quality of this study and elevating the academic standard of the paper.
我仔细考虑了您的每一个建议,并相应地修改了手稿。你们的专家意见对于提高本研究的质量和论文的学术水平起到了至关重要的作用。
Once again, I sincerely thank you for your hard work and valuable time. Your contributions are indispensable in ensuring the quality of academic research and advancing our field.
再次衷心感谢您的辛勤工作和宝贵的时间。您的贡献对于确保学术研究的质量和推进我们的领域是不可或缺的。
Here are we feedback:
以下是我们的反馈:
Reviewer #2:
评论者#2:
1.Clarify Ablation Selection Criteria: It would be helpful to expand on the clinical decision-making criteria used to select MWA versus RFA, beyond equipment availability. For example, were there specific patient characteristics that guided the choice of technique? This would help contextualize the applicability of each ablation modality.
1.明确消融选择标准:除了设备可用性之外,扩展用于选择 MWA 与 RFA 的临床决策标准将很有帮助。例如,是否有特定的患者特征来指导技术的选择?这将有助于了解每种消融方式的适用性。
Thank you for your valuable comment regarding the ablation selection criteria. We would like to clarify that, as stated in our Methods section, “each center had its own technical expertise and equipment availability, either specializing in MWA or RFA. The choice between MWA and RFA was therefore primarily determined by the patient's geographical location and the center's capabilities.” As we acknowledged in our Discussion section (limitations paragraph): all procedures were performed by highly experienced experts, which may limit the generalizability of the results, and the choice of treatment (MWA or RFA) was primarily determined by the expertise and equipment availability at each center, rather than by individual patient characteristics or lesion features. While this approach helped reduce selection bias in treatment modality, it may not fully reflect the individualized clinical decision-making typically seen in real-world practice.
感谢您对消融选择标准提出的宝贵意见。我们想澄清的是,正如我们的方法部分所述, “每个中心都有自己的技术专长和设备可用性,要么专门从事 MWA,要么专门从事 RFA。因此,MWA 和 RFA 之间的选择主要取决于患者的地理位置和中心的能力。”正如我们在讨论部分(限制段落)中承认的那样:所有程序均由经验丰富的专家执行,这可能会限制结果的普遍性,并且治疗的选择(MWA 或 RFA)主要取决于专业知识和设备可用性每个中心,而不是根据个体患者特征或病变特征。虽然这种方法有助于减少治疗方式的选择偏差,但它可能无法完全反映现实世界实践中常见的个体化临床决策。
2.Confounding Control and Sensitivity Analysis: While your use of IPW and PSM techniques is commendable, I recommend including additional details on the sensitivity analysis conducted. A clearer description of how potential residual confounding was addressed would further support the reliability of your conclusions.
2.混杂控制和敏感性分析:虽然您对 IPW 和 PSM 技术的使用值得赞扬,但我建议包括有关所进行的敏感性分析的其他详细信息。更清晰地描述如何解决潜在的残留混杂因素将进一步支持您的结论的可靠性。
We appreciate the reviewer's suggestions. Regarding confounding factor control and sensitivity analyses, we implemented multiple approaches to ensure the reliability of our results. Initially, we conducted PSM, subsequently employed IPW methodology with weight trimming, both yielding consistent results. Furthermore, we performed subgroup analyses (Figure 5) investigating the impact of various baseline characteristics on treatment outcomes, which serves as an additional form of sensitivity analysis. Moreover, we utilized logistic regression models to evaluate the influence of ablation approach on outcomes (presented in Supplementary Material 2), designating ablation approach as the independent variable and adjusting for covariates, calculating p value, adjusted odds ratios with corresponding 95% confidence intervals. The integration of these analytical methods enables a comprehensive assessment of potential residual confounding effects on study outcomes, thereby substantiating the reliability of our conclusions. We will elaborate on these sensitivity analyses in the revised manuscript to demonstrate our measures for controlling potential confounding factors more explicitly. We again express our gratitude for your valuable feedback.
我们感谢审稿人的建议。在混杂因素控制和敏感性分析方面,我们采用了多种方法来确保结果的可靠性。最初,我们进行了 PSM,随后采用了 IPW 方法和权重调整,两者都产生了一致的结果。此外,我们还进行了亚组分析(图 5),调查各种基线特征对治疗结果的影响,这是敏感性分析的另一种形式。此外,我们利用逻辑回归模型来评估消融方法对结果的影响(在补充材料2中介绍),指定消融方法作为自变量并调整协变量s ,计算p 值,调整优势比与相应的 95% 置信区间。这些分析方法的整合能够全面评估对研究结果的潜在残留混杂影响,从而证实我们结论的可靠性。我们将在修订稿中详细阐述这些敏感性分析,以更明确地展示我们控制潜在混杂因素的措施。我们再次对您的宝贵反馈表示感谢。
Discuss Generalizability of Patient Population: The study focuses on SHPT patients with CKD from a multicenter cohort, which strengthens generalizability. However, discussing the limitations of this population with respect to broader patient demographics would provide additional context on the applicability of the findings.
讨论患者群体的普遍性:该研究重点关注来自多中心队列的患有 CKD 的 SHPT 患者,这增强了普遍性。然而,讨论该人群相对于更广泛的患者人口统计的局限性将为研究结果的适用性提供更多背景。
We appreciate your valuable feedback regarding the external validity of our study. We have carefully considered your suggestion about discussing the limitations of our patient population in a broader context. Accordingly, we have incorporated a detailed discussion of the study's external validity in the "Discussion" section: "...particularly given that patients were predominantly in advanced stages of CKD, potentially underrepresenting those in early stages or with different comorbidities...while the multicenter design enhanced external validity by including diverse clinical settings and patient demographics, geographical and ethnic representation remained limited, potentially affecting the generalizability of our findings across different populations...Given these limitations, future studies with larger sample sizes, more rigorous randomized controlled designs, and extended follow-up periods are needed to validate our findings, better understand the long-term therapeutic benefits of this intervention, and comprehensively explore the influence of these factors' interactions on treatment selection."
我们感谢您对我们研究的外部有效性提出的宝贵反馈。我们仔细考虑了您关于在更广泛的背景下讨论我们患者群体的局限性的建议。因此,我们在“讨论”部分对该研究的外部有效性进行了详细讨论:“......特别是考虑到患者主要处于 CKD 晚期阶段,可能低估了早期阶段或患有不同合并症的患者......同时多中心设计通过纳入不同的临床环境和患者人口统计数据来增强外部有效性,地理和种族代表性仍然有限,可能会影响我们的研究结果在不同人群中的普遍性……鉴于这些限制,未来的研究需要更大的样本量、更严格的随机对照需要设计和延长随访时间来验证我们的研究结果,更好地了解这种干预措施的长期治疗益处,并全面探讨这些因素的相互作用对治疗选择的影响。 ”
We believe these additions provide a more comprehensive context for the applicability of our findings. We are grateful for your insightful suggestions.
我们相信这些补充为我们的研究结果的适用性提供了更全面的背景。我们感谢您富有洞察力的建议。
Balance of Groups and Propensity Score Model: Your transition from PSM to IPW to maintain statistical power is a strong point. I suggest elaborating on the specific covariates chosen for the propensity score model and how these selections contributed to achieving balance post-weighting
群体平衡和倾向评分模型:从 PSM 过渡到 IPW 以保持统计能力是一个强项。我建议详细说明为倾向评分模型选择的具体协变量以及这些选择如何有助于实现权重后的平衡.
We appreciate your attention to covariate selection in our propensity score model. In the Methods section, we noted the incorporation of preoperative serum PTH, phosphorus levels[1,2], and parathyroid gland size[3] as covariates in propensity score modeling, selected based on their well-documented associations with SHPT treatment outcomes in the literature. By incorporating these covariates, we aimed to minimize selection bias and confounding effects. Following weighting, we assessed covariate balance through standardized mean differences, which demonstrated satisfactory equilibrium between MWA and RFA groups. Detailed results of these assessments are presented in the "Results" section, with accompanying Love plots (see Supplementary Material 1) to visually demonstrate the improvement in balance. We believe these supplementary explanations enhance the transparency and scientific rigor of our analysis. We are grateful for your valuable feedback, which has helped us further refine our study.
感谢您关注我们的倾向评分模型中的协变量选择。在方法部分,我们注意到将术前血清 PTH、磷水平[1,2]和甲状旁腺大小[3]作为倾向评分模型中的协变量,这些因素是根据其与 SHPT 治疗结果之间有充分记录的关联而选择的。文学。通过合并这些协变量,我们的目标是最大限度地减少选择偏差和混杂效应。加权后,我们通过标准化均值差评估协变量平衡,这证明了 MWA 和 RFA 组之间令人满意的平衡。这些评估的详细结果显示在“结果”部分,并附有 Love 图(参见补充材料1 ),以直观地展示平衡性的改善。我们相信这些补充解释增强了我们分析的透明度和科学严谨性。我们感谢您的宝贵反馈,这有助于我们进一步完善我们的研究。
[1] Steinl GK, Kuo JH. Surgical Management of Secondary Hyperparathyroidism. Kidney Int Rep. 2020;6(2):254-264. Published 2020 Dec 30. doi:10.1016/j.ekir.2020.11.023
[1] 斯坦尔·GK,郭建华.继发性甲状旁腺功能亢进症的手术治疗。肾脏国际报告 2020;6(2):254-264。发布于 2020 年 12 月 30 日。doi:10.1016/j.ekir.2020.11.023IF: 5.7 Q1 IF: 5.7 Q1
[2]Lin LP, Lin M, Wu SS, et al. Complications after radiofrequency ablation of hyperparathyroidism secondary to chronic kidney disease. Ren Fail. 2023;45(1):2215334. doi:10.1080/0886022X.2023.2215334IF: 3.0 Q1
[2]林列平,林明,吴诗诗,等。继发于慢性肾脏病的甲状旁腺功能亢进症射频消融术后的并发症。任失败。 2023;45(1):2215334。号码:10.1080/0886022X.2023.2215334
[3]Issa PP, Kandil E, Lee GS. Radiofrequency ablation as a treatment modality for primary hyperparathyroidism: a systematic literature review. Gland Surg. 2024;13(1):87-99. doi:10.21037/gs-22-546
[3]伊萨·PP,坎迪尔·E,李·GS。射频消融作为原发性甲状旁腺功能亢进症的治疗方式:系统文献综述。腺外科。 2024;13(1):87-99。 doi:10.21037/gs-22-546IF: 1.5 Q3
Define Complication Criteria: The outcome measures are relevant and clinically meaningful. However, explicitly defining criteria for complications, particularly transient versus persistent hypocalcemia, would enhance clarity and standardize interpretation across readers.
定义并发症标准:结果测量是相关的且具有临床意义。然而,明确定义并发症的标准,特别是短暂性与持续性低钙血症的标准,将提高读者的清晰度并标准化解释。
We appreciate your attention to the definition of complications in our study. In the figure legends beneath Table 3, we have explicitly delineated the criteria for complications. Specifically, persistent hypoparathyroidism is defined as a sustained decline in parathyroid function extending beyond 6 months[1], while persistent voice hoarseness is characterized by a sustained reduction in vocal pitch and volume persisting for more than 6 months[2]. The definitions of transient and persistent hypocalcemia were established based on clinical significance and existing literature standards[3]. We believe these definitions enhance the clarity of our results and provide readers with a consistent interpretative framework.
我们感谢您关注我们研究中并发症的定义。在表 3 下面的图例中,我们明确描述了并发症的标准。具体来说,持续性甲状旁腺功能减退症被定义为甲状旁腺功能持续下降超过6个月[1] ,而持续性声音嘶哑的特点是音调和音量持续下降持续超过6个月[2] 。短暂性和持续性低钙血症的定义是根据临床意义和现有文献标准建立的[3] 。我们相信这些定义增强了我们结果的清晰度,并为读者提供了一致的解释框架。
Walker Harris V, Jan De Beur S. Postoperative hypoparathyroidism: medical and surgical therapeutic options. Thyroid. 2009;19(9):967-973. doi:10.1089/thy.2008.0306
Walker Harris V,Jan De Beur S。术后甲状旁腺功能减退症:药物和手术治疗选择。甲状腺。 2009;19(9):967-973。 doi:10.1089/thy.2008.0306IF: 5.8 Q1
Christakis I, Klang P, Talat N, Galata G, Schulte KM. Long-term quality of voice is usually acceptable after initial hoarseness caused by a thyroidectomy or a parathyroidectomy. Gland Surg. 2019;8(3):226-236. doi:10.21037/gs.2018.09.02
克里斯塔基斯 I、巴生 P、塔拉特 N、加拉塔 G、舒尔特 KM。在甲状腺切除术或甲状旁腺切除术引起的最初声音嘶哑后,长期的声音质量通常是可以接受的。腺外科。 2019;8(3):226-236。 doi:10.21037/gs.2018.09.02IF: 1.5 Q3
Liu J, et al. Risk factors predicting severe hypocalcemia after total parathyroidectomy without autotransplantation in patients with secondary hyperparathyroidism. J Int Med Res. 2020;48(1):0300060519897505.
刘杰等人。继发性甲状旁腺功能亢进症患者行甲状旁腺全切除术而不进行自体移植后预测严重低钙血症的危险因素。国际医学研究杂志。 2020;48(1):0300060519897505。
Consider Longer Follow-up: The 24-month follow-up period is appropriate; however, I encourage mentioning the potential value of even longer follow-up, particularly regarding recurrence rates. This could be suggested as a recommendation for future studies to assess the durability of ablation outcomes.
考虑更长的随访时间:24个月的随访时间是合适的;然而,我鼓励提及更长时间随访的潜在价值,特别是在复发率方面。这可以作为未来研究评估消融结果持久性的建议。
We appreciate your focus on our study's follow-up duration. We concur that the 24-month follow-up period is appropriate for evaluating short- and intermediate-term outcomes. However, we acknowledge that an extended follow-up period would be invaluable for assessing the long-term efficacy and recurrence rates of ablative therapies. Consequently, we have suggested in the discussion section that future investigations consider longer follow-up periods to more comprehensively evaluate the durability and stability of ablation outcomes.
我们感谢您对我们研究的后续持续时间的关注。我们同意 24 个月的随访期适合评估短期和中期结果。然而,我们承认,延长随访期对于评估消融疗法的长期疗效和复发率非常有价值。因此,我们在讨论部分建议未来的研究考虑更长的随访期,以更全面地评估消融结果的持久性和稳定性。
We have incorporated the following content in the Discussion section: "we employed a 24-month follow-up period to evaluate the efficacy and safety profiles of MWA and RFA in treating SHPT. While this duration is adequate for assessing short- and intermediate-term outcomes, we acknowledge that a more extended follow-up period would be necessary to comprehensively evaluate the long-term efficacy and recurrence rates of ablative therapies. Given these limitations, future studies with larger sample sizes, more rigorous randomized controlled designs, and prolonged follow-up periods are needed to validate our findings and better understand the long-term therapeutic benefits of this intervention."
我们在讨论部分纳入了以下内容: “我们采用了 24 个月的随访期来评估 MWA 和 RFA 治疗 SHPT 的疗效和安全性。虽然这个持续时间足以评估短期和中期鉴于这些局限性,我们承认需要更长的随访期来全面评估消融疗法的长期疗效和复发率,未来的研究需要更大的样本量、更严格的随机对照设计和更长的随访时间。需要一段时间来验证我们的发现并更好地了解这种干预措施的长期治疗益处。”
Data Interpretation in Subgroups: The subgroup analysis by variables such as preoperative PTH and nodule size is insightful. Additional discussion on the interaction of these factors may help in identifying patient profiles best suited for MWA or RFA.
亚组数据解释:通过术前 PTH 和结节大小等变量进行的亚组分析很有洞察力。对这些因素相互作用的进一步讨论可能有助于确定最适合 MWA 或 RFA 的患者概况。
We appreciate your recommendations regarding our study. In the current investigation, we conducted subgroup analyses and calculated interaction p-values for several factors. However, no significant interactions were observed (all interaction p-values > 0.05), suggesting comparable therapeutic efficacy between MWA and RFA regardless of these patient characteristics.
我们感谢您对我们的研究提出的建议。在当前的调查中,我们进行了亚组分析并计算了多个因素的交互作用 p 值。然而,没有观察到显着的相互作用(所有相互作用 p 值 > 0.05),这表明无论这些患者特征如何,MWA 和 RFA 之间的治疗效果相当。
Nevertheless, we concur that this remains a worthy area for further investigation. Future studies with larger sample sizes and extended follow-up periods could explore more comprehensively the influence of these factors' interactions on treatment selection. We have incorporated the following section in the discussion: "although our subgroup analyses revealed no significant interactions between treatment effects and factors such as preoperative PTH levels or nodule size (all interaction p-values > 0.05), this remains an area warranting further investigation. Given these limitations, future studies with larger sample sizes, more rigorous randomized controlled designs, and extended follow-up periods are needed to validate our findings, better understand the long-term therapeutic benefits of this intervention, and comprehensively explore the influence of these factors' interactions on treatment selection."
尽管如此,我们一致认为这仍然是一个值得进一步研究的领域。未来具有更大样本量和延长随访期的研究可以更全面地探讨这些因素相互作用对治疗选择的影响。我们在讨论中纳入了以下部分:“尽管我们的亚组分析显示治疗效果与术前 PTH 水平或结节大小等因素之间没有显着的相互作用(所有相互作用 p 值 > 0.05),但这仍然是一个值得进一步研究的领域鉴于这些局限性,未来需要更大的样本量、更严格的随机对照设计和更长的随访时间来验证我们的研究结果,更好地了解这种干预措施的长期治疗益处,并全面探讨这些干预措施的影响。因素相互作用对治疗选择的影响。”
Discussion and Comparison with Literature: The discussion is well-developed, though I recommend expanding the comparison with studies on MWA and RFA for primary hyperparathyroidism. Highlighting distinctions in outcomes between primary and secondary cases could enrich the context and provide further insights for clinical practice.
与文献的讨论和比较:尽管我建议扩大与原发性甲状旁腺功能亢进症 MWA 和 RFA 研究的比较,但讨论已经很充分了。强调原发性病例和继发性病例之间结果的区别可以丰富背景并为临床实践提供进一步的见解。
We appreciate your meticulous review and suggestions regarding our study. We concur that comparing MWA and RFA outcomes between primary and secondary hyperparathyroidism could provide more profound insights for clinical practice. In the revised manuscript, we have expanded the discussion section to highlight the distinctions in outcomes between these two variants, supported by relevant literature citations. We have incorporated the following content in the discussion: "In comparative studies of primary and secondary hyperparathyroidism, both MWA and RFA have demonstrated efficacy. However, primary cases typically involve single gland pathology, whereas secondary cases often present with multiglandular hyperplasia, potentially leading to divergent treatment outcomes. Studies on primary hyperparathyroidism have demonstrated high success rates for ablation, achieving an overall cure rate of 91.2%[30]. In contrast, secondary cases, due to their multiglandular nature, may present an elevated risk of incomplete ablation and recurrence."
我们感谢您对我们研究的细致审查和建议。我们一致认为,比较原发性和继发性甲状旁腺功能亢进症的 MWA 和 RFA 结果可以为临床实践提供更深刻的见解。在修订稿中,我们扩展了讨论部分,以突出这两种变体之间结果的区别,并得到相关文献引用的支持。我们在讨论中加入了以下内容:“在原发性和继发性甲状旁腺功能亢进症的比较研究中,MWA和RFA均显示出疗效。然而,原发病例通常涉及单腺体病理,而继发性病例往往表现为多腺体增生,可能导致对原发性甲状旁腺功能亢进症的研究表明,消融的成功率很高,总体治愈率可达 91.2% [30],而继发性甲状旁腺功能亢进症由于其多腺体性质,可能会达到 91.2% 的治愈率。存在较高的不完全消融和复发风险。”
Strengths and Limitations: While you note the multicenter design as a strength, it would benefit the manuscript to discuss potential biases from non-randomized treatment allocation and other limitations more thoroughly. Greater transparency here would strengthen readers' confidence in the findings.
优点和局限性:虽然您注意到多中心设计是一种优点,但更彻底地讨论非随机治疗分配和其他限制的潜在偏差将有利于手稿。更大的透明度将增强读者对调查结果的信心。
We appreciate the reviewer's valuable suggestions and fully acknowledge the importance of expanding the discussion of study limitations. In the original manuscript's discussion section, we have thoroughly elaborated on the study's limitations, particularly regarding the potential impact of non-randomized treatment allocation. Specifically, the selection of microwave ablation and radiofrequency ablation was primarily determined by geographical location and center capabilities. While this allocation method may somewhat reduce treatment selection bias, we recognize that it might not fully reflect the individualized decision-making process in real clinical practice. To mitigate bias from non-random allocation, we employed inverse probability weighting statistical methods to balance covariate distributions between groups and conducted additional sensitivity analyses (see Supplementary Materials 2) to address potential residual confounding. However, we explicitly acknowledge that even with these statistical approaches, the influence of unobserved confounders may persist. Furthermore, our study is limited by the modest sample size and lack of vitamin D level assessment. The fact that all procedures were performed by experienced specialists may also affect the generalizability of our results. Based on the reviewer's suggestions, we will further expand this section in the revised manuscript to provide a more in-depth discussion of how these limitations potentially influence the interpretation of our findings, emphasizing the need for larger randomized controlled trials to validate our observations.
我们感谢审稿人的宝贵建议,并充分认识到扩大研究局限性讨论的重要性。在原稿的讨论部分,我们彻底阐述了该研究的局限性,特别是关于非随机治疗分配的潜在影响。具体而言,微波消融和射频消融的选择主要根据地理位置和中心能力来决定。虽然这种分配方法可能会在一定程度上减少治疗选择偏差,但我们认识到它可能无法完全反映实际临床实践中的个体化决策过程。为了减轻非随机分配的偏差,我们采用逆概率加权统计方法来平衡组之间的协变量分布,并进行额外的敏感性分析(参见补充材料2 )以解决潜在的残留混杂因素。然而,我们明确承认,即使采用这些统计方法,未观察到的混杂因素的影响可能仍然存在。此外,我们的研究受到样本量较小和缺乏维生素 D 水平评估的限制。所有程序均由经验丰富的专家执行这一事实也可能会影响我们结果的普遍性。根据审稿人的建议,我们将在修订稿中进一步扩展这一部分,以更深入地讨论这些限制如何可能影响我们研究结果的解释,强调需要更大规模的随机对照试验来验证我们的观察结果。
Minor Revisions for Clarity: The manuscript is well-written overall but could benefit from minor grammatical and typographical refinements to improve readability. Simplifying technical explanations, particularly those surrounding ablation techniques, may aid comprehension for a broader audience.
为了清晰度而进行的小修改:手稿总体写得很好,但可以从语法和排版上的细微改进中受益,以提高可读性。简化技术解释,特别是那些围绕消融技术的解释,可能有助于更广泛的受众的理解。
Thank you for your thoughtful comments. We will implement the following revisions: First, we will meticulously review the manuscript's grammar and formatting to ensure fluidity and structural clarity. Particular attention will be paid to the transitions and coherence between paragraphs to enhance readability and comprehension. Second, regarding technical explanations, particularly the descriptions of MWA and RFA in the Introduction section, we will implement appropriate simplifications. This section will be reformulated using more concise and accessible language to elucidate the principles and characteristics of these ablation techniques, reducing excessive technical details to accommodate a broader readership. Simultaneously, we will maintain the necessary academic rigor, ensuring informational accuracy while simplifying the presentation.
感谢您的深思熟虑的评论。我们将进行以下修改:首先,我们将仔细审查稿件的语法和格式,以确保流畅性和结构清晰。将特别注意段落之间的过渡和连贯性,以增强可读性和理解性。其次,对于技术解释,特别是引言部分中MWA和RFA的描述,我们将进行适当的简化。本节将使用更简洁和易于理解的语言重新阐述,以阐明这些消融技术的原理和特征,减少过多的技术细节以适应更广泛的读者群。同时,我们将保持必要的学术严谨性,确保信息准确性,同时简化演示。
Reviewer #5
评论者#5
The authors have modified the revised manuscript as suggested therefore the manuscript should be accepted for the publication.
作者已按照建议修改了修订稿,因此该稿件应被接受出版。
We sincerely thank Reviewer #5 for the careful review of our manuscript and the valuable suggestions provided during the revision process. Your constructive feedback has helped us improve the clarity and readability of our paper, making it more accessible to a broader audience while maintaining its academic rigor.
我们衷心感谢5号审稿人对我们的稿件的仔细审阅以及在修订过程中提供的宝贵建议。您的建设性反馈帮助我们提高了论文的清晰度和可读性,使其更容易被更广泛的受众所理解,同时保持其学术严谨性。
Reviewer #6
评论者 #6
Thank you for the opportunity to review the revised manuscript. After carefully examining the authors' responses and the updated content, I have several persistent concerns:
感谢您有机会审阅修改后的手稿。在仔细检查了作者的回复和更新的内容后,我有几个持续存在的担忧:
Sample Size and Statistical Analysis: In the initial review, I raised significant concerns about the insufficient sample size for conducting reliable logistic regression analysis, citing the "one in ten rule" for Events per Variable (EPV). Upon careful examination of the authors' response document, I find that they have completely failed to address this critical issue. The authors provided no response whatsoever to this fundamental methodological concern. This silence on such a crucial aspect of the study's design and analysis is deeply troubling. The current sample size remains inadequate to support the proposed statistical analyses, potentially invalidating the study's results and conclusions.
样本量和统计分析:在初步审查中,我对样本量不足以进行可靠的逻辑回归分析表示了严重担忧,并引用了每个变量事件 (EPV) 的“十分之一规则”。经过仔细审查作者的回应文件,我发现他们完全没有解决这个关键问题。作者没有对这一基本方法论问题做出任何回应。对研究设计和分析的如此重要方面的沉默令人深感不安。目前的样本量仍然不足以支持拟议的统计分析,可能使研究结果和结论无效。
Thank you for your continued attention to the statistical methodology, particularly regarding the '10 events per variable' rule. We have carefully considered your concern and would like to clarify that we have revised our analytical approach. Rather than analyzing factors affecting treatment failure (which had limited events), we have now focused on analyzing factors associated with treatment success. In our current analysis, we observed 160 successful cases (achievement of target PTH levels) out of 182 total patients, with five predictor variables in the final multivariate model. This provides 32 events per variable, well exceeding the '10 events per variable' rule. Beyond the logistic regression analysis, we employed multiple complementary statistical approaches, including:
感谢您对统计方法的持续关注,特别是“每个变量 10 个事件”规则。我们仔细考虑了您的担忧,并想澄清一下,我们已经修改了分析方法。我们现在不再分析影响治疗失败的因素(其事件有限),而是专注于分析与治疗成功相关的因素。在我们当前的分析中,我们观察了 182 名患者中的 160 名成功病例(达到目标 PTH 水平),最终多变量模型中有5 个预测变量。这为每个变量提供了32 个事件,远远超出了“每个变量 10 个事件”的规则。除了逻辑回归分析之外,我们还采用了多种互补的统计方法,包括:
Inverse probability weighting to balance potential confounders
逆概率加权以平衡潜在的混杂因素
Generalized linear mixed models for longitudinal analysis of biochemical parameters
用于生化参数纵向分析的广义线性混合模型
Subgroup analyses across different patient characteristics
不同患者特征的亚组分析
Sensitivity analyses (detailed in Supplementary Materials 2)
敏感性分析(详见补充材料2 )
We appreciate your rigorous review which has helped us improve the statistical robustness of our study.
我们感谢您的严格审查,这帮助我们提高了研究的统计稳健性。
Data Discrepancies and Adjustments: Reviewer #5 identified inconsistencies in the reported data. The authors' swift modification of these figures to achieve matching values raises serious questions about the integrity and reliability of the data. Such ad hoc adjustments undermine the credibility of the entire study.
数据差异和调整:审稿人 #5 发现报告数据中存在不一致之处。作者对这些数字进行快速修改以实现匹配值,这引发了有关数据完整性和可靠性的严重问题。这种临时调整破坏了整个研究的可信度。
We sincerely appreciate the reviewer's meticulous examination of our data and significant concerns regarding data consistency. We take these concerns with utmost seriousness, as data integrity is fundamental to scientific research. We wish to clarify that the adjustments made were not arbitrary modifications but corrections of errors that occurred during data consolidation. The correct figures are 86 cases in the microwave ablation (MWA) group and 96 cases in the radiofrequency ablation (RFA) group. In the interest of complete transparency, we have reverified the consistency of all original data from each participating center with our database entries; we have thoroughly reviewed all data and corrected this error in the revised manuscript. We would be willing to provide the raw data for verification if required, and we apologize for any confusion this may have caused.
我们衷心感谢审稿人对我们数据的细致检查以及对数据一致性的重大关注。我们非常严肃地对待这些问题,因为数据完整性是科学研究的基础。我们希望澄清,所做的调整并非任意修改,而是对数据合并过程中发生的错误的更正。正确的数字是微波消融(MWA)组86例,射频消融(RFA)组96例。为了完全透明,我们重新验证了每个参与中心的所有原始数据与我们数据库条目的一致性;我们已经彻底审查了所有数据并在修订稿中纠正了这个错误。如果需要,我们愿意提供原始数据进行验证,对于由此可能造成的任何混乱,我们深表歉意。
Methodological Concerns: The authors' decision to proceed with complex statistical analyses on an insufficient sample size, coupled with the identified data discrepancies and subsequent alterations, casts significant doubt on the study's overall validity and reproducibility.
方法论问题:作者决定对样本量不足进行复杂的统计分析,加上已发现的数据差异和随后的更改,使人们对该研究的整体有效性和可重复性产生了重大怀疑。
We sincerely appreciate the reviewer's comprehensive evaluation and concerns regarding our study's validity, reproducibility, and data discrepancies. Firstly, regarding the noted data discrepancies, these represent corrections of initial misinterpretations rather than alterations of data. We have now thoroughly examined and verified all data to ensure accuracy and consistency throughout the manuscript. We are prepared to provide raw data for verification if required.
我们衷心感谢审稿人对我们研究的有效性、可重复性和数据差异的全面评估和关注。首先,关于所指出的数据差异,这些差异代表了对最初误解的纠正,而不是对数据的更改。我们现在已经彻底检查和验证了所有数据,以确保整个手稿的准确性和一致性。如果需要,我们准备提供原始数据以供验证。
Concerning the study's validity and reproducibility, we emphasize that our findings align substantially with previously published results in this field. For instance, our target PTH achievement rates (88.37% for MWA and 87.50% for RFA) correspond with previously reported outcomes [1-3]. Similarly, our observed complication profile, with transient hypocalcemia as the predominant complication, aligns with documented findings in previous studies. This consistency with existing literature substantiates the validity of our findings.
关于该研究的有效性和可重复性,我们强调我们的研究结果与该领域之前发表的结果基本一致。例如,我们的目标 PTH 实现率(MWA 为 88.37%,RFA 为 87.50%)与之前报告的结果相对应 [ 1-3 ]。同样,我们观察到的并发症概况(以短暂性低钙血症为主要并发症)与之前研究中记录的结果一致。这种与现有文献的一致性证实了我们研究结果的有效性。
While acknowledging that a larger sample size would be ideal, our study encompasses 182 patients from five centers, representing one of the larger comparative studies in this field. To address potential limitations in sample size and selection bias, we employed inverse probability weighting instead of the initially planned propensity score matching to preserve all available data, thereby maximizing statistical power. This approach enabled us to balance confounding factors while maintaining the complete sample size. Furthermore, we conducted comprehensive sensitivity analyses (detailed in Supplementary Material 2) to verify the robustness of our findings. We maintain that our statistical methodology is appropriate for the available data and provides valuable insights into the comparative effectiveness of these treatments. While acknowledging these limitations in our discussion section, we advocate for larger randomized controlled trials to further validate our findings.
虽然我们承认较大的样本量是理想的,但我们的研究涵盖了来自五个中心的 182 名患者,代表了该领域较大的比较研究之一。为了解决样本量和选择偏差的潜在限制,我们采用逆概率加权而不是最初计划的倾向评分匹配来保留所有可用数据,从而最大化统计功效。这种方法使我们能够平衡混杂因素,同时保持完整的样本量。此外,我们还进行了全面的敏感性分析(详见补充材料2 ),以验证我们研究结果的稳健性。我们坚持认为,我们的统计方法适合现有数据,并为这些治疗的比较有效性提供了有价值的见解。在我们的讨论部分承认这些局限性的同时,我们主张进行更大规模的随机对照试验来进一步验证我们的发现。
[1] Peng C, Zhang Z, Liu J, Chen H, Tu X, Hu R, et al. Efficacy and safety of ultrasound-guided radiofrequency ablation of hyperplastic parathyroid gland for secondary hyperparathyroidism associated with chronic kidney disease. Head Neck. 2017 Mar;39(3):564-571. doi: 10.1002/hed.24657IF: 2.3 Q1 .
[1]彭春,张正,刘杰,陈红,涂晓,胡瑞,等。超声引导下射频消融增生性甲状旁腺治疗慢性肾脏病相关继发性甲状旁腺功能亢进症的疗效和安全性。头颈。 2017 年 3 月;39(3):564-571。 doi:10.1002/hed.24657
。
[2] Chen CC, Chen HL, Chiang PL, et al. Efficacy and safety of radiofrequency ablation for primary and secondary hyperparathyroidism with or without previous parathyroidectomy: a retrospective study. Int J Hyperthermia. 2022;39(1):907-917. doi:10.1080/02656736.2022.2097324IF: 3.0 Q2
[2]陈CC,陈HL,蒋PL,等。射频消融治疗原发性和继发性甲状旁腺功能亢进症(有或没有既往甲状旁腺切除术)的疗效和安全性:一项回顾性研究。 Int J 热疗。 2022;39(1):907-917。号码:10.1080/02656736.2022.2097324
[3] Gong L, Tang W, Lu J, Xu W. Thermal ablation versus parathyroidectomy for secondary hyperparathyroidism: A meta-analysis. Int J Surg. 2019;70:13-18. doi:10.1016/j.ijsu.2019.08.004IF: 12.5 Q1
[3]龚丽,唐伟,陆健,徐伟。热消融与甲状旁腺切除术治疗继发性甲状旁腺功能亢进症的荟萃分析。国际外科杂志。 2019;70:13-18。 doi:10.1016/j.ijsu.2019.08.004
Novelty and Clinical Significance: The authors' response to the criticism regarding the lack of innovation in this study remains unsatisfactory. As previously noted, and echoed by Reviewer #8, thermal ablation techniques (microwave ablation vs. radiofrequency ablation) for secondary hyperparathyroidism are already well-established in clinical guidelines and consensus statements. The current study fails to provide substantial new insights or meaningful advancements in this field.
新颖性和临床意义:作者对有关本研究缺乏创新的批评的回应仍然不能令人满意。如前所述,并得到第 8 号审稿人的赞同,继发性甲状旁腺功能亢进症的热消融技术(微波消融与射频消融)已在临床指南和共识声明中得到确立。目前的研究未能在该领域提供实质性的新见解或有意义的进展。
Clinical Impact: Given the aforementioned concerns, I maintain my original assessment that this study does not offer substantial insights or practical benefits for clinical practice in the treatment of secondary hyperparathyroidism (SHPT) with ablation techniques.
临床影响:鉴于上述担忧,我维持原来的评估,即这项研究没有为利用消融技术治疗继发性甲状旁腺功能亢进症 (SHPT) 的临床实践提供实质性见解或实际益处。
In conclusion, while I appreciate the authors' efforts to address the initial reviews, the fundamental issues regarding sample size, data integrity, and clinical significance persist. These shortcomings significantly limit the scientific value and potential impact of this research. I recommend that the authors consider conducting a more robust study with an adequate sample size and rigorous methodological approach to meaningfully contribute to the field.
总之,虽然我赞赏作者为解决初步审查所做的努力,但有关样本量、数据完整性和临床意义的基本问题仍然存在。这些缺点极大地限制了这项研究的科学价值和潜在影响。我建议作者考虑进行一项更稳健的研究,提供足够的样本量和严格的方法论,以便为该领域做出有意义的贡献。
We appreciate the reviewer's concerns regarding our study's novelty and clinical impact. While thermal ablation techniques for SHPT treatment are indeed established in clinical guidelines, we believe our study makes several meaningful contributions and offers practical benefits to clinical practice:
我们感谢审稿人对我们研究的新颖性和临床影响的担忧。虽然 SHPT 治疗的热消融技术确实已在临床指南中确立,但我们相信我们的研究做出了一些有意义的贡献,并为临床实践提供了实际好处:
Firstly, this represents the first prospective, multicenter comparative study directly evaluating MWA versus RFA for SHPT treatment. Although both techniques are established, direct comparative studies guiding clinical decision-making were previously lacking. Our research addresses this significant knowledge gap by providing direct evidence of their comparative efficacy and safety.
首先,这是第一个直接评估 MWA 与 RFA 对于 SHPT 治疗的前瞻性、多中心比较研究。尽管这两种技术都已建立,但以前缺乏指导临床决策的直接比较研究。我们的研究通过提供其相对功效和安全性的直接证据来解决这一重大知识差距。
Secondly, despite both MWA and RFA being established treatments, clinicians often face uncertainty when selecting between these options. Our direct comparison provides evidence-based guidance for treatment selection, demonstrating comparable efficacy and safety profiles between the techniques. This information is particularly valuable for centers considering implementing either technology.
其次,尽管 MWA 和 RFA 都是既定的治疗方法,但临床医生在选择这些选项时常常面临不确定性。我们的直接比较为治疗选择提供了基于证据的指导,证明了这些技术之间可比较的疗效和安全性。该信息对于考虑实施任一技术的中心特别有价值。
Thirdly, our analysis identifies post-procedure 2-hour parathyroid hormone (PTH) levels as an independent predictor of treatment success. To our knowledge, this is the first study demonstrating the predictive value of early post-ablation PTH levels for treatment outcomes in SHPT patients undergoing thermal ablation. ROC curve analysis revealed an area under the curve of 0.843, with 80% sensitivity and 81.2% specificity at a post-ablation 2-hour PTH cutoff value of 372 pg/mL.
第三,我们的分析将术后 2 小时甲状旁腺激素 (PTH) 水平确定为治疗成功的独立预测因子。据我们所知,这是第一项证明早期消融后 PTH 水平对接受热消融的 SHPT 患者治疗结果的预测价值的研究。 ROC 曲线分析显示曲线下面积为 0.843,消融后 2 小时 PTH 截止值为 372 pg/mL 时灵敏度为 80%,特异性为 81.2%。
Fourthly, our subgroup analyses demonstrate maintained efficacy of both techniques across varying patient characteristics. This information, particularly relevant for personalized treatment approaches, has not been previously reported in the literature.
第四,我们的亚组分析表明,这两种技术在不同患者特征下均保持疗效。这些信息,特别是与个性化治疗方法相关的信息,此前尚未在文献中报道过。
Fifthly, our comprehensive analysis of complications and their management strategies provides practical guidance for preventing and handling adverse events. The detailed documentation of technical parameters, including ablation protocols and safety measures, offers valuable reference for clinical implementation.
第五,我们对并发症及其处理策略的全面分析为预防和处理不良事件提供了实用指导。详细的技术参数记录,包括消融方案和安全措施,为临床实施提供了宝贵的参考。
Additionally, our multicenter design with standardized protocols and detailed technical parameters provides practical guidance for clinical implementation, addressing real-world variability in center expertise and equipment availability.
此外,我们的多中心设计具有标准化协议和详细的技术参数,为临床实施提供实用指导,解决中心专业知识和设备可用性的现实变化。
While acknowledging that the fundamental techniques are established, we maintain that these novel research aspects provide meaningful clinical insights for patient care and treatment selection in SHPT management.
在承认基本技术已经建立的同时,我们认为这些新颖的研究方面为 SHPT 管理中的患者护理和治疗选择提供了有意义的临床见解。
Reviewer #12
评论者 #12
Thank you to the authors for following the reviewer's and editorial recommendations.
感谢作者遵循审稿人和编辑的建议。
We would like to express our sincere gratitude to Reviewer #12 for taking the time to review our manuscript. Your guidance, along with the editorial recommendations, has been invaluable in improving the quality of our paper. We appreciate your recognition of our efforts to address all the suggested revisions.
我们衷心感谢 12 号审稿人花时间审阅我们的手稿。您的指导以及编辑建议对于提高我们论文的质量非常宝贵。感谢您对我们为解决所有建议修订所做的努力的认可。
Thank editors and reviewers once again for your constructive feedback; it has significantly contributed to enhancing the quality of my research.
再次感谢编辑和审稿人的建设性反馈;它对提高我的研究质量做出了重大贡献。