Characterization of Disease Patterns in Children with Intracranial Abscesses for Enhanced Clinical Decision-Making
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsQ1: Introduction: The background and context are clear, and the justification for this study is well presented. However, I suggest expanding the rationale for the retrospective time frame chosen (December 2022 to May 2023) and how the observed cases might relate to broader epidemiological trends.
Q2: Introduction: It would be beneficial to mention any recent changes in the incidence of intracranial abscesses in children (such as the potential influence of post-pandemic respiratory infections, which is mentioned later but not connected here).
Q3: Methods: The methodology is well explained, but the use of statistical tools such as "Cramer’s V" and "Fisher’s exact test" could benefit from a brief explanation of why these tests were chosen for the specific data types analyzed. Please address why Fisher’s exact test was preferred over other potential tests for smaller datasets (like chi-square) could provide better scientific justification.　 For readers less familiar with these methods, it would be helpful to provide context on how a Cramer’s V value of 0.7 indicates a strong association.
Q4: Methods:it would be helpful to clarify the exclusion criteria, specifically why meningitis and meningoencephalitis were excluded.
Q5:Methods: The paper references p-values, but it might be helpful to briefly explain how p-value thresholds were chosen (e.g., ≤ 0.05).
Q6: Methods The patient inclusion criteria mention the use of ICD-10 codes to identify relevant cases. This section would benefit from additional details about how potential cases were screened or cross-verified. For instance, explain whether any misclassified cases were identified and how those were handled, particularly the processes used to ensure the accuracy of diagnosis.
Q7: Results: The statistical analysis appears sound, but it would be beneficial to provide more detailed interpretations of key findings (e.g., sinusitis correlation with Streptococcus pyogenes). You may consider to extend in your results by explaining what this means for day-to-day clinical decision-making. Will earlier recognition of sinusitis as a risk factor for certain pathogens change diagnostic procedures and/or treatment protocols?
Q8 Results: Outcomes: When discussing outcomes, it would be useful to relate the clinical sequlae (e.g., left-sided paralysis) to potential long-term quality-of-life impacts on pediatric patients. Are these residual symptoms common in other studies, and how might this study’s findings influence prognosis or rehabilitation efforts?
Q9: Results: This section is very data-heavy, which can make it difficult for readers to interpret. Rewrite and reorganize the content may help your potential readers easily follow your thinking flow.
Q10: Some figures (e.g., Figure 1) contain a lot of data, but the presentation is slightly crowded. It might be beneficial to separate these into multiple figures or ensure they are more legible for readers when published.
Q11: Discussion: While the discussion is thorough, it might benefit from greater integration with the findings. Consider explicitly linking each major finding from the results to a corresponding explanation or comparison to existing literature. A specific statement about the limitations posed by the small sample size (9 cases) and the retrospective nature of the study should he high-lighted in this part.
Q12: Discussion: You mention that streptococci were the most common pathogens. Have you considered that the pathogen patterns you identified consistent globally, or might there be regional differences due to healthcare practices, climate, or other factors?
Q13: discussion: the discussion highlights that the prevalence of anaerobic bacteria is higher than commonly reported—this finding should be further explored. Could this point to potential environmental or hospital-specific factors? Addressing these could make the contribution of your paper clearer.
Q14 Discussion: While the study followed a particular treatment regimen, the absence of abscess drainage in your cases is noted but not explained in detail. Given that abscess drainage is a common practice in some centers, adding a brief discussion about the decision to forego drainage (citing relevant studies) could help readers understand this choice.
Q15 Discussion: Although the discussion briefly acknowledges the retrospective design and small sample size, a dedicated section discussing limitations in greater detail would enhance the transparency of the study. In addition to the small sample size, consider discussing any potential biases in data collection (e.g., reliance on medical records) or limitations in the statistical analyses used.
Q16 Discussion:: A strengths section (or incorporation into the discussion) could highlight the aspects of the study that make it robust, such as the detailed collection of clinical data and the use of advanced statistical methods like Cramer’s V to explore correlations in this dataset.
Q17: Line 134: You mentioned that all your cases did not receive drainage, but in the conclusion part you mentioned that Prompt surgical drainage of the abscess should be aimed Abscess drainage was not used in any case. Traditionally, surgical drainage is preferred over non-invasive treatments. Further elaboration on why abscess drainage was not employed
Q18. Conclusion: While you mention the need for larger, multicenter studies, you could also suggest specific avenues for future research. For instance, would a prospective study on the use of rapid PCR for pathogen identification be feasible? What about investigating the long-term outcomes of children with residual neurological effects?
Q19:Line 98, 100: "55,56%" should be corrected to "55.56%"
Q20: Line 15,58, 73, 94, 137, 177, and 203 : “nine cases” of intracranial infections were analyzed from “eight patients." could be confusing. (line 74). Please clarify that one patient had two separate infections, if that is the case.
Q21: Line 99: "10,22" should be "10.22"
Author Response
Q1: Introduction: The background and context are clear, and the justification for this study is well presented. However, I suggest expanding the rationale for the retrospective time frame chosen (December 2022 to May 2023) and how the observed cases might relate to broader epidemiological trends.
We appreciate the reviewer's comment regarding the specified timeframe. The study's retrospective period (December 2022 to May 2023) was deliberately chosen due to an observed cluster of intracranial abscesses in children during this period. The initial hypothesis postulated a possible effect of the easing of COVID-19 pandemic restrictions and a potentially reduced exposure to post-pandemic respiratory infections during that time. Brain abscesses are exceedingly rare, making this specific time window valuable for further analysis. The rationale was to derive statistical-based clinical characteristics from this specific patient cohort to enhance understanding of this generally under-researched condition.
Q2: Introduction: It would be beneficial to mention any recent changes in the incidence of intracranial abscesses in children (such as the potential influence of post-pandemic respiratory infections, which is mentioned later but not connected here).
Thank you for your insightful feedback. Accorsi eta al. 2023 indicate a recent change in the incidence of pediatric intracranial infections. The study, using data from 37 children's hospitals across 19 states and the District of Columbia from January 2016 to March 2023, observed a higher-than-expected number of these infections starting in August 2021, culminating in a large peak during the winter of 2022–2023. This increase followed a period of lower-than-expected cases after the onset of the COVID-19 pandemic. The report suggests a potential link between this rise and increased circulation of respiratory pathogens during the winter of 2022-2023. This timeframe aligns with the post-lockdown period mentioned, suggesting a potential correlation [1].
Q3: Methods: The methodology is well explained, but the use of statistical tools such as "Cramer’s V" and "Fisher’s exact test" could benefit from a brief explanation of why these tests were chosen for the specific data types analyzed. Please address why Fisher’s exact test was preferred over other potential tests for smaller datasets (like chi-square) could provide better scientific justification.　 For readers less familiar with these methods, it would be helpful to provide context on how a Cramer’s V value of 0.7 indicates a strong association.
In response to the concerns raised regarding our statistical methodology, we would like to clarify our choice of Fisher's Exact Test and Cramer’s V for analyzing the categorical data. Fisher's Exact Test was specifically selected due to its appropriateness for small sample sizes; unlike the Chi-Square Test, which requires a minimum expected frequency that can be difficult to achieve in smaller datasets, Fisher's Exact Test delivers precise probability calculations without such constraints. This ensures the validity of our results, particularly when dealing with rare events. Additionally, we utilized Cramer’s V which is a measure of association between two categorical variables, ranging from 0 to 1. A Cramer’s V value of 0 indicates no association, while a value closer to 1 indicates a stronger association. A Cramer’s V value of 0.7 suggests a strong association between the variables being analyzed. This implies that changes in one variable are closely related to changes in another, indicating potentially significant underlying relationships that warrant further investigation. This high association suggests that changes in one variable are closely linked to changes in another, highlighting potentially significant dynamics within our data. Together, these statistical tools provide a robust framework for analyzing our findings and support a deeper understanding of the associations present in our study.
Q4: Methods: it would be helpful to clarify the exclusion criteria, specifically why meningitis and meningoencephalitis were excluded.
Thank you for your insightful feedback regarding our exclusion criteria. We chose to exclude cases of meningitis and meningoencephalitis to focus specifically on neurosurgical patients where clear surgical interventions were indicated. Meningitis and meningoencephalitis often present with complex clinical features that can confound our analysis, as they involve inflammation of the membranes surrounding the brain and can lead to a range of neurological complications that are not directly amenable to surgical intervention. By concentrating on cases requiring neurosurgical procedures, we aimed to produce more homogeneous study groups, allowing for more accurate assessments of surgical outcomes and treatment efficacy. This focused approach ensures that our findings are relevant and applicable to the specific patient population undergoing surgical intervention, ultimately contributing to more targeted clinical insights. We appreciate the opportunity to clarify this rationale.
Q5: Methods: The paper references p-values, but it might be helpful to briefly explain how p-value thresholds were chosen (e.g., ≤ 0.05).
Thank you for your thoughtful comment. The p-values in our analysis were interpreted according to conventional statistical standards, with a threshold set at ≤ 0.05 to denote statistical significance. This threshold is widely accepted in the field and signifies a 5% probability that the observed results could be due to random chance. P-values exceeding this threshold were considered statistically non-significant, indicating insufficient evidence to reject the null hypothesis.
Moreover, we recognize that while a p-value of 0.05 serves as a common benchmark, it is essential to interpret these values in the context of the study design and the clinical relevance of the findings. In our results, we emphasize that statistical significance does not necessarily equate to clinical significance, and we encourage careful consideration of both when making clinical decisions. Thank you for the opportunity to clarify how p-value thresholds were chosen in our analysis.
Q6: Methods The patient inclusion criteria mention the use of ICD-10 codes to identify relevant cases. This section would benefit from additional details about how potential cases were screened or cross-verified. For instance, explain whether any misclassified cases were identified and how those were handled, particularly the processes used to ensure the accuracy of diagnosis.
In response to the reviewer’s request for clarification regarding our methods for case identification, we appreciate the opportunity to provide further details. Our patient inclusion criteria relied on ICD-10 codes to systematically identify relevant cases. To enhance the reliability of our findings, we implemented a rigorous screening process where potential cases were cross-verified against clinical records. This involved a manual review of diagnosis notes to ensure accurate classification and to identify any misclassified cases. If any misclassifications were detected, we employed a standardized protocol to reassess those cases, which included consultation with clinical experts and re-evaluation of diagnostic criteria. This careful approach not only ensured the accuracy of our diagnoses but also reinforced the integrity of our dataset. By prioritizing thorough validation, we aimed to minimize any potential biases and enhance the robustness of our study's conclusions. Thank you for highlighting this aspect, as we believe it is crucial for understanding the precision of our analytical approach.
Q7: Results: The statistical analysis appears sound, but it would be beneficial to provide more detailed interpretations of key findings (e.g., sinusitis correlation with Streptococcus pyogenes). You may consider to extend in your results by explaining what this means for day-to-day clinical decision-making. Will earlier recognition of sinusitis as a risk factor for certain pathogens change diagnostic procedures and/or treatment protocols?
Thank you for your constructive feedback regarding the interpretation of our findings. The correlation, e.g. between sinusitis and Streptococcus pyogenes, particularly in the context of intracranial abscesses in children, underscores the need for heightened clinical awareness. Recognizing sinusitis as a risk factor for these serious infections may lead clinicians to adopt more proactive diagnostic strategies, such as a lower threshold for conducting MRI when children present with sinusitis and concerning neurological symptoms. Additionally, this insight could prompt earlier consideration of antibiotic therapy tailored to target Streptococcus pyogenes in these cases. By implementing these changes in diagnostic and treatment protocols, we can facilitate earlier intervention, potentially preventing the progression to severe complications like brain abscesses which then might need an emergency surgery. We appreciate the chance to clarify the practical implications of our results, emphasizing their importance in day-to-day clinical decision-making for pediatric patients.
Q8 Results: Outcomes: When discussing outcomes, it would be useful to relate the clinical sequalae (e.g., left-sided paralysis) to potential long-term quality-of-life impacts on pediatric patients. Are these residual symptoms common in other studies, and how might this study’s findings influence prognosis or rehabilitation efforts?
Thank you for your insightful feedback regarding the discussion of outcomes related to clinical sequelae and their long-term impacts on quality of life for pediatric patients. In our study, we acknowledge that the presence and severity of residual symptoms, such as left-sided paralysis, are associated on the location of the abscess and the specific cerebral compartments affected. Research highlights that the timing of intervention is critical, as “time is brain”. Delays in treatment can lead to significant exacerbation of neurological deficits. For example, complications such as space-occupying lesions, midline shift, elevated intracranial pressure, and herniation can occur rapidly and may culminate in adverse outcomes, including death.
In reviewing related literature of Bodilsen et al. 2024, it’s evident that neurological deficits (and epilepsy) affect approximately 70% of adult survivors. A study in this paper shows long-term consequences impacting employment and disability pensions in adults. Inferring from this to children, a sequelae such as left-sided paralysis would significantly affect their daily life, education, and social interactions, resulting in considerable long-term quality-of-life impacts. The paper highlights as well the crucial role of specialized neurorehabilitation in regaining functional capacity, emphasizing the need for proactive intervention given the potential severity of such deficits. Therefore, its findings strongly support the reviewer's point about considering the long-term consequences of residual symptoms [2].
Furthermore, understanding these potential long-term sequelae is crucial for informing prognosis and tailoring rehabilitation efforts. Early intervention strategies focusing on physical and occupational therapy may facilitate better recovery of motor function and enhance overall quality of life. Additionally, ongoing neuropsychological assessment is important to address cognitive and emotional difficulties that may arise post-treatment.
In summary, our findings underscore the importance of early diagnosis and intervention in managing pediatric cerebral abscesses to minimize residual neurological deficits. By integrating our findings with existing research, we hope to contribute to a better understanding of the prognosis associated with this condition and the need for comprehensive rehabilitation programs to support affected pediatric patients.
Q9: Results: This section is very data-heavy, which can make it difficult for readers to interpret. Rewrite and reorganize the content may help your potential readers easily follow your thinking flow.
Thank you for your valuable feedback regarding the Results section of our manuscript. We appreciate your concern about its data-heavy nature, and we have taken your suggestion to reorganize the content for improved clarity and readability. We have restructured the Results section into the following key subsections: Epidemiology; Clinical Symptoms; Treatment; Etiology and Statistical Feature Correlation Analysis. By implementing this new structure, we aim to enhance the flow of information and facilitate a more accessible interpretation of the data for our readers.
Q10: Some figures (e.g., Figure 1) contain a lot of data, but the presentation is slightly crowded. It might be beneficial to separate these into multiple figures or ensure they are more legible for readers when published.
Thank you for your feedback regarding Figure 1. We appreciate your perspective and would like to provide some context for our design choices. We believe that the current arrangement of the data in Figure 1 enhances clarity and allows for a comprehensive understanding of the relationships presented. The layout was carefully structured to ensure that all relevant information is included. We prioritized a balance between detail and readability, striving to present the data in a manner that is both informative and accessible. Additionally, we aimed to create a figure that conveys a complete narrative at a glance, which can be beneficial for readers seeking to grasp the wider implications of the results quickly. By maintaining the current design, we hope to facilitate connections between different data points that might be lost if the information were separated into multiple figures. We appreciate your insights and believe that our current approach effectively communicates the key findings of the descriptive analysis of our study.
Q11: Discussion: While the discussion is thorough, it might benefit from greater integration with the findings. Consider explicitly linking each major finding from the results to a corresponding explanation or comparison to existing literature. A specific statement about the limitations posed by the small sample size (9 cases) and the retrospective nature of the study should he high-lighted in this part.
Thank you for your thoughtful feedback on the discussion section. We appreciate your suggestions and would like to elaborate on how we will incorporate them into our revision. In Section 4.1 of the discussion, we have begun to place the results of the descriptive analysis in the context of the current literature. However, we will ensure that the significant findings from the results is explicitly linked to a corresponding explanation or comparison to existing studies. This will strengthen the integration of our findings and highlight their relevance within the broader research landscape.
Regarding the limitations posed by the small sample size (9 cases) and the retrospective nature of the study, we agree that this is an important point. We will include specific statements about these limitations in the discussion and further elaborate on their implications to provide a balanced view of our study’s strengths and challenges section. We believe these adjustments will enhance the discussion and contribute to a more thorough understanding of our findings.
Q12: Discussion: You mention that streptococci were the most common pathogens. Have you considered that the pathogen patterns you identified consistent globally, or might there be regional differences due to healthcare practices, climate, or other factors?
Regarding this question, Bodilsen et al. 2024 showed that. the most common causative pathogens in community-acquired brain abscesses are oral cavity bacteria, including the Streptococcus anginosus group, Fusobacterium spp., and Aggregatibacter spp., often associated with dental and chronic ear infections.Less frequent causes include Staphylococcus aureus and Gram-negative bacilli in post-neurosurgical brain abscesses, Mycobacterium tuberculosis in endemic areas, and Nocardia spp., fungi, and parasites in severely immunocompromised individuals. Historically, risk factors included head trauma, cyanotic congenital heart disease, and chronic ear infections; however, in recent decades, dental infections and immunocompromise have also become significant predisposing conditions [2]. Additionally, emerging molecular diagnostics have significantly expanded the ability to identify pathogens, particularly anaerobic bacteria (115 of 173 cases) of brain abscesses caused by oral cavity bacteria which aligns with our findings [2].
The reviewer raised an important point regarding the potential for regional differences in pathogen patterns. While there may not be specific literature directly linking pediatric brain abscesses with climate change, it is widely recognized that climate change influences infectious diseases more broadly [3]. Furthermore, social, demographic, cultural, and financial factors generally exert a significant influence on health outcomes. It is essential to recognize that access to and utilization of rapid diagnostics and therapies can display both intra- and interregional disparities, which must be considered, especially in pediatric health care. Moreover, the COVID-19 pandemic has further complicated these dynamics, significantly impacting the availability and accessibility of healthcare services for children. Disruptions in routine immunizations, delays in diagnosis and treatment, and increased mental health challenges during this period have exacerbated existing inequalities. It is crucial to acknowledge these aspects as they play a critical role in understanding health equity and ensuring that all populations can receive timely and effective care [4].
Q13: discussion: the discussion highlights that the prevalence of anaerobic bacteria is higher than commonly reported—this finding should be further explored. Could this point to potential environmental or hospital-specific factors? Addressing these could make the contribution of your paper clearer.
Bodilsen et al. 2024 support the reviewer's comment and aligns with findings regarding anaerobic infections in children with intracranial abscesses. The guidelines extensively discuss the role of oral cavity bacteria (often anaerobic) as a significant cause of community-acquired brain abscesses, stating that they are "often associated with dental and chronic ear infections". The meta-analysis revealed a significantly higher prevalence of anaerobic bacteria than previously reported, prompting the reviewer's request for further exploration of potential environmental or hospital-specific factors contributing to this finding. Therefore, the paper's findings are directly relevant to the prevalence of anaerobic infections in this population, and addressing the reviewer's concerns regarding potential contributing factors would strengthen the paper's contribution by clarifying the reasons behind the observed higher prevalence of anaerobic bacteria.
In addition to that, Antibiotic stewardship is crucial in managing brain abscesses, as highlighted in the guidelines' discussion of treatment duration and oral antimicrobial transition. The optimal duration of antimicrobial therapy requires balancing the risk of relapse/recurrence with the potential for drug toxicity and the principles of antimicrobial stewardship. The guidelines acknowledge the frequent use of oral consolidation therapy after intravenous treatment, but also emphasize the need to weigh potential benefits against increased risks of drug reactions and antimicrobial stewardship considerations. The lack of robust evidence regarding early oral antimicrobial transition highlights the importance of judicious antibiotic use, emphasizing a need for further research in this area.
Q14 Discussion: While the study followed a particular treatment regimen, the absence of abscess drainage in your cases is noted but not explained in detail. Given that abscess drainage is a common practice in some centers, adding a brief discussion about the decision to forego drainage (citing relevant studies) could help readers understand this choice.
Thank you for your thoughtful feedback regarding the absence of abscess drainage in our study. We appreciate your suggestion to provide additional context for our decision. Our rationale for not performing abscess drainage was based on several considerations. Firstly, available literature does not definitively demonstrate that abscess drainage is superior to radical evacuation in terms of patient outcomes. In examining the literature, it is evident that – on the one hand - open surgical techniques present several advantages in clinical practice. Particularly, the study indicates that these methods may lower the need for further imaging, surgical interventions, and antibiotic therapy. This reduction can lead to a more streamlined patient management pathway, thereby minimizing the associated complications of additional treatments. [5] On the other hand, the approach of Double-Cavity Sleeve Tube combines the beneficial aspects of both burr hole aspiration and open craniotomy. By integrating these techniques, clinicians can provide a more accessible and less invasive treatment option for patients. This not only simplifies the procedural approach but also enhances patient safety and comfort, making it a compelling choice for managing complex cases. [6] Additionally, our cases involved acute, large, space-occupying abscesses, which presented a potentially life-threatening clinical scenario for the children involved. In such situations, we believed that radical intervention was warranted to address the urgency and severity of the clinical presentation.
Q15 Discussion: Although the discussion briefly acknowledges the retrospective design and small sample size, a dedicated section discussing limitations in greater detail would enhance the transparency of the study. In addition to the small sample size, consider discussing any potential biases in data collection (e.g., reliance on medical records) or limitations in the statistical analyses used.
Thank you for your valuable feedback regarding the discussion of limitations in our study. We completely agree that a dedicated section addressing limitations would enhance the transparency and rigor of our work.
Our study has several limitations that must be acknowledged. First, it employed a retrospective design, which can introduce biases related to data collection and interpretation and limits our ability to establish causal relationships. Additionally, our reliance on medical records for data extraction may contribute to data collection bias, as the accuracy and completeness of these records can vary; thus, any missing or incomplete data may influence our findings. Furthermore, the patients included in our study were drawn from a specific clinical setting, which raises concerns about selection bias and limits the generalizability of our findings to broader populations or different healthcare environments. Lastly, our statistical analyses were constrained by the small sample size, potentially affecting the power to detect significant differences or associations and leading to the possibility of overlooking important findings.
We appreciate your suggestion for a more comprehensive discussion of these limitations, and created a new strengths and limitations Section
Q16 Discussion:: A strengths section (or incorporation into the discussion) could highlight the aspects of the study that make it robust, such as the detailed collection of clinical data and the use of advanced statistical methods like Cramer’s V to explore correlations in this dataset.
Thank you for your insightful suggestion to incorporate a strengths section into the discussion. In response to your feedback, we have added a dedicated section that highlights the robust aspects of our study. We emphasize the meticulous collection of clinical data, which enhances the reliability and validity of our findings. Furthermore, we employed advanced statistical methods such as Cramer’s V to explore correlations within our dataset. This approach not only allows us to quantify the strength of associations between variables but also adds depth to our analysis, ultimately contributing to a more nuanced understanding of the relationships we examined. We believe that addressing these strengths will enhance the overall quality of our discussion and provide readers with a clearer appreciation of the rigor behind our research. A new strengths and limitations Section is created.
Q17: Line 134: You mentioned that all your cases did not receive drainage, but in the conclusion part you mentioned that Prompt surgical drainage of the abscess should be aimed Abscess drainage was not used in any case. Traditionally, surgical drainage is preferred over non-invasive treatments. Further elaboration on why abscess drainage was not employed
Thank you for your careful review and observation regarding the terminology used in our manuscript. We acknowledge the inconsistency in our phrasing, where we mentioned "drainage" instead of accurately referring to "evacuation." We revised the text accordingly to clarify that the implantation of an abscess drainage was not employed in any of our cases. As well, we implemented a detailed explanation for our rationale.
Q18. Conclusion: While you mention the need for larger, multicenter studies, you could also suggest specific avenues for future research. For instance, would a prospective study on the use of rapid PCR for pathogen identification be feasible? What about investigating the long-term outcomes of children with residual neurological effects?
Thank you for your thoughtful suggestions regarding future research directions. We agree that a prospective study on the use of rapid PCR for pathogen identification is an excellent idea. Implementing rapid PCR could enhance the accuracy and speed of pathogen identification, potentially leading to more tailored and effective treatment strategies for patients. This approach may also help in reducing the time to appropriate therapy, which is crucial in managing infections effectively.
Regarding the long-term outcomes of children with residual neurological effects, we established an own discussion section now. Additionally, we perform follow-up assessments of the patients. These follow-ups take place during outpatient visits at intervals of 3, 6, 12, and 24 months. By monitoring these patients over time, we aim to gather valuable data on their neurological outcomes and further inform the management of similar cases in the future.
Q19:Line 98, 100: "55,56%" should be corrected to "55.56%"
Thank you very much. We adapted this.
Q20: Line 15,58, 73, 94, 137, 177, and 203 : “nine cases” of intracranial infections were analyzed from “eight patients." could be confusing. (line 74). Please clarify that one patient had two separate infections, if that is the case.
Thank you very much. We adapted this.
Q21: Line 99: "10,22" should be "10.22"
Thank you very much. We adapted this.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Comments and Suggestions for AuthorsYour manuscript has been reviewed. Although I found merit in your study, I have raised a number of major concerns that preclude its acceptance in the present form. I would therefore be grateful if you would consider these points and send a suitably revised manuscript.
Comments to the author
General
Main suggestions are to consider reviewing with a native English speaker. This retrospective monocentric study aims to explore the clinical features associated with intracranial abscesses to identify specific disease patterns that can expedite management in clinical practice. Due to its non specific clinical symptoms, this pathology is quit tricky to diagnose promptly and subsequently start an appropriate treatment. The main objective of the study is rather vague and should be focused on a major specific target. Furthermore, the single-center retrospective nature of the study limits some of the evaluations and inferences the authors were able to make. The discussion should be more detailed as well.
Specific
Line 131 “As soon as an intracranial abscess was suspected, a cMRI imaging was performed.” In how many cases the CT scan was performed as well?
Line 193 “The prevalence of streptococci and staphylococci mirrors the distribution observed in previous studies. Our study highlights that anaerobes constitute a larger proportion than what is commonly reported in the existing literature” Please add more details and numbers concerning the data expressed in other studies.
Line 208 “Based on our study, the high prevalence of sinusitis with the above-mentioned pathogens as the underlying cause of the development of intracranial infections goes in line with the current literature” To enrich to discussion, please add more data concerning mastoiditis, its impact on intracranial abscesses and its relationship with your mentioned pathogens. Please make reference to “Sarno LD, Cammisa I, Curatola A, Pansini V, Eftimiadi G, Gatto A, Chiaretti A. A scoping review of the management of acute mastoiditis in children: What is the best approach? Turk J Pediatr. 2023;65(6):906-918. doi: 10.24953/turkjped.2023.320. PMID: 38204305.”
Comments on the Quality of English Language
Your manuscript has been reviewed. Although I found merit in your study, I have raised a number of major concerns that preclude its acceptance in the present form. I would therefore be grateful if you would consider these points and send a suitably revised manuscript.
Comments to the author
General
Main suggestions are to consider reviewing with a native English speaker. This retrospective monocentric study aims to explore the clinical features associated with intracranial abscesses to identify specific disease patterns that can expedite management in clinical practice. Due to its non specific clinical symptoms, this pathology is quit tricky to diagnose promptly and subsequently start an appropriate treatment. The main objective of the study is rather vague and should be focused on a major specific target. Furthermore, the single-center retrospective nature of the study limits some of the evaluations and inferences the authors were able to make. The discussion should be more detailed as well.
Specific
Line 131 “As soon as an intracranial abscess was suspected, a cMRI imaging was performed.” In how many cases the CT scan was performed as well?
Line 193 “The prevalence of streptococci and staphylococci mirrors the distribution observed in previous studies. Our study highlights that anaerobes constitute a larger proportion than what is commonly reported in the existing literature” Please add more details and numbers concerning the data expressed in other studies.
Line 208 “Based on our study, the high prevalence of sinusitis with the above-mentioned pathogens as the underlying cause of the development of intracranial infections goes in line with the current literature” To enrich to discussion, please add more data concerning mastoiditis, its impact on intracranial abscesses and its relationship with your mentioned pathogens. Please make reference to “Sarno LD, Cammisa I, Curatola A, Pansini V, Eftimiadi G, Gatto A, Chiaretti A. A scoping review of the management of acute mastoiditis in children: What is the best approach? Turk J Pediatr. 2023;65(6):906-918. doi: 10.24953/turkjped.2023.320. PMID: 38204305.”
Author Response
Main suggestions are to consider reviewing with a native English speaker.
Thank you for your suggestion regarding the review of our manuscript by a native English speaker. We have taken this recommendation seriously and have thoroughly revised the text. This review has helped us improve the clarity, coherence, and overall quality of the language used in the manuscript.
This retrospective monocentric study aims to explore the clinical features associated with intracranial abscesses to identify specific disease patterns that can expedite management in clinical practice. Due to its non specific clinical symptoms, this pathology is quit tricky to diagnose promptly and subsequently start an appropriate treatment. The main objective of the study is rather vague and should be focused on a major specific target.
Thank you for your insightful feedback regarding the clarity and specificity of the study's main objective. We acknowledge that the initial phrasing may have seemed vague, and we appreciate the opportunity to clarify our aims. This retrospective monocentric study was conducted during a specific timeframe (December 2022 to May 2023) due to an observed cluster of intracranial abscesses in children during this period. Our primary hypothesis focused on a potential association between the easing of COVID-19 pandemic restrictions and implications for respiratory infections post-pandemic, which could impact the incidence of brain abscesses. Given that these abscesses are extremely rare, analyzing this particular time window allows us to derive valuable statistical insights into the clinical features of the condition. Our intent is to identify specific disease patterns that will enhance the understanding of this generally under-researched pathology and expedite management in clinical practice. The objective is articulated more explicitly in the revised manuscript to reflect this focused approach.
Furthermore, the single-center retrospective nature of the study limits some of the evaluations and inferences the authors were able to make. The discussion should be more detailed as well.
Thank you for your constructive feedback regarding the limitations of our single-center retrospective study. We have carefully reviewed and revised the discussion section to provide a more detailed analysis of our findings, ensuring that we address the implications of our study's design. Additionally, we have added a comprehensive Strengths and Limitations section to clearly outline the advantages and constraints of our research. This section highlights the insights gained from our specific clinical setting while acknowledging the limitations inherent to a single-center study, including potential biases and the need for further validation in multi-center cohorts. We appreciate your suggestion, as it has allowed us to enhance the rigor and clarity of our discussion.
Specific
Line 131 “As soon as an intracranial abscess was suspected, a cMRI imaging was performed.” In how many cases the CT scan was performed as well?
Thank you for your question regarding the imaging modalities used in our study. To clarify, in none of the cases was a CT scan (cCT) performed. The modality of choice for suspected intracranial abscesses in emergency situations was an MRI, as it provides superior soft tissue contrast and avoids the potential radiation exposure associated with CT scans, which can pose long-term risks, especially in pediatric populations. We have emphasized this in the updated manuscript.
Line 193 “The prevalence of streptococci and staphylococci mirrors the distribution observed in previous studies. Our study highlights that anaerobes constitute a larger proportion than what is commonly reported in the existing literature” Please add more details and numbers concerning the data expressed in other studies.
Thank you for your constructive feedback regarding anaerobic pathogen distribution. Please have a look at the answer of Q13 where we discussed this in detail.
Line 208 “Based on our study, the high prevalence of sinusitis with the above-mentioned pathogens as the underlying cause of the development of intracranial infections goes in line with the current literature” To enrich to discussion, please add more data concerning mastoiditis, its impact on intracranial abscesses and its relationship with your mentioned pathogens. Please make reference to “Sarno LD, Cammisa I, Curatola A, Pansini V, Eftimiadi G, Gatto A, Chiaretti A. A scoping review of the management of acute mastoiditis in children: What is the best approach? Turk J Pediatr. 2023;65(6):906-918. doi: 10.24953/turkjped.2023.320. PMID: 38204305.”
Thank you for your thoughtful suggestions. Brain abscesses are encapsulated collections of pus that can be caused by various pathogens, including bacteria, mycobacteria, fungi, protozoa, or helminths. Acute mastoiditis (AM), an infection of the mastoid bone behind the ear, can lead to life-threatening intracranial complications such as brain abscesses. The Streptococcus anginosus group pathogens, which have the potential to cause head and neck space infections, including intracranial abscesses, are increasingly being implicated in mastoiditis. In a recent study, complications of mastoiditis, including meningitis, brain abscess, and sinus vein thrombosis, were more common in adults than in children. The mentioned paper highlights the lack of consensus on the optimal management of AM, suggesting a complex interplay of factors influencing its development and progression. The fact that conservative management (including antibiotics) shows a relatively low success rate (24.6% for antibiotics alone) suggests the possibility of severe complications, including potentially intracranial infections if the infection is not adequately controlled. Furthermore, the high success rate of mastoidectomy (97%) underscores the severity that AM can reach. Given the proximity of the mastoid air cells to the brain, it's plausible that untreated or poorly treated AM could lead to intracranial complications. [7]
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsAccepted.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript can be accepted in present form
