Change in clinical parameters after subgingival instrumentation for the treatment of periodontitis and timing of periodontal re-evaluation: A systematic review and meta-analysis.

AIM: To evaluate the changes in periodontal parameters (reduction in probing pocket depth [PPD], gain in clinical attachment level [CAL] and reduction in full-mouth bleeding on probing [BoP]) after subgingival instrumentation of periodontal pockets at different time points in systemically healthy patients suffering from periodontitis. MATERIALS AND METHODS: Four databases were searched for RCTs that carried out subgingival instrumentation in periodontal pockets and evaluated PPD at a minimum of two consecutive time points other than baseline. The analysis was conducted for both all pocket depths and stratified for initially shallow (4-5 mm) and deep (≥6 mm) pockets and data were extracted for various time points, 1-2, 3-4 and 5-6 months. Weighted mean effects (WMEs) were calculated with 95% confidence interval (CI) and predictive intervals were calculated. RESULTS: Twenty-nine RCTs were identified, and all of them were included in the meta-analysis. The results showed that for both shallow and deep pockets there was a small though clinically meaningful change between 1- to 2-month and 3- to 4-month time points and between these and 5-6 months. CONCLUSIONS: In systemically healthy patients, the greater part of reduction in PPD and gain in CAL occurs within the first 1-2 months after subgingival instrumentation. However, additional benefits in terms of pocket depth reduction occur beyond these early time points.

Re-evaluation of the reduced heart weights in male rats in a 28-day oral repeated-dose toxicity study of tetramethylammonium hydroxide.

We recently conducted a detailed hazard assessment of tetramethylammonium hydroxide (TMAH), a priority chemical substance under the Japan Chemical Substances Control Law. During this assessment, there was debate regarding the reduced heart weight observed in the treated male groups in the 28-day rat oral repeated-dose toxicity study. This finding was not observed in females in this study and in both sexes of oral toxicity studies for tetramethylammonium chloride (TMAC) or tetramethylammonium hydrogen phthalate (TMAHP). Unpublished individual data from the oral TMAH developmental and reproductive toxicity (DART) screening study were also obtained; no effect on heart weight was observed. In addition, background data on rat heart weight from six 28-day oral toxicity studies conducted in the same facility, year, strain, age, and breeder as the TMAH study were obtained from the Japan Existing Chemical Substances Database (JECDB). These investigations suggest that the statistically significant lower heart weight in the treated males in the 28-day toxicity study is likely caused by an incidental skewing of individuals with heavier heart weights toward control male groups and is not due to TMAH treatment. Thus, it is worthwhile to include as much relevant data as possible to confirm or refute unexpected findings in toxicity studies.

Identification of the anti-inflammatory quality markers of Chrysanthemi Flos (Juhua) using spectrum-effect relationships combined with bioactivity re-evaluation.

Chrysanthemi Flos (Juhua), an edible herbal medicine that possesses efficacies of dispersing wind, clearing heat and detoxifying. Studies have demonstrated that the health benefits of Chrysanthemi Flos are largely attributable to its anti-inflammatory effects. However, the correlation between the compounds monitored by the current quality control methods and the anti-inflammatory effects of Chrysanthemi Flos is unclear. In order to better control the quality of Chrysanthemi Flos, the identification of anti-inflammatory quality markers (Q-markers) of Chrysanthemi Flos was performed. The chemical components of Chrysanthemi Flos were profiled by HPLC fingerprints combined with chemometrics methods. Simultaneously, the anti-inflammatory activities of 10 batches of water extracts of Chrysanthemi Flos were evaluated in lipopolysaccharide-activated RAW 264.7 macrophages cells. Gray correlation analysis was performed to assess the relationship between the anti-inflammatory activity and chemical properties. The results showed that 13 common peaks were closely correlated with the anti-inflammatory effect, and further bioactivity re-evaluation confirmed that 10 known compounds exerted a strong anti-inflammatory effect. The quantitative analysis of the 10 Q-markers showed that the 25 batches of samples could be discriminated into different zones according to their producing areas. Conclusively, the present work identified 10 anti-inflammatory Q-markers of Chrysanthemi Flos using spectrum-effect relationships combined with bioactivity re-evaluation.

[Challenges and Influencial Factors in Autism-Specific Diagnostics in Toddlers]. / Herausforderungen und Einflussfaktoren bei der autismusspezifischen Diagnostik im Kleinkindalter.

Challenges and Influencial Factors in Autism-Specific Diagnostics in Toddlers Abstract. Objective: What are the particular challenges that make early diagnosis of young children difficult in the clinical routine? What recommendations can be derived from this in practice? Methods: Our interdisciplinary social pediatric team examined 31 toddlers aged 2 to 3 years twice in intervals of 6-9 months in the for outpatient diagnostics regarding suspected autism spectrum disorder (ASD). In addition, we conducted an online survey with further experts. Results: After the first anamnestic interview, 8 of the 31 (26 %) children were diagnosed with a differential diagnosis of ASD. Comorbid disorders, familial peculiarities, and challenges posed by the examination setting and anamnesis made a reliable clinical classification difficult. Conclusion: In our experience, many toddlers can only receive a valid diagnosis after a follow-up examination after starting one or more therapies and regularly carrying out these therapies over a period of 6-9 months and possibly also after structural changes have taken place (care in nursery, implementation of youth welfare measures, or similar).

Re-evaluation of neurobehavioural toxicity of clothianidin using statistical methods for ordered alternatives assuming dose-response effect.

Neurobehavioural toxicity of clothianidin in previous studies was re-evaluated using statistical methods for ordered alternatives assuming a dose-response effect. In a maternal exposure study, clothianidin was added into the diet to provide levels of 0% (control), 0.002%, 0.006% and 0.018% during the gestation and lactation periods in mice. In exploratory behaviour of male offspring in the F1 generation, average speed increased significantly in a dose-related manner in the Jonckheere test. Total distance lengthened in the high-dose group and average speed increased in the high-dose group in the Shirley-Williams test. In a two-generation toxicity study, clothianidin was added in the diet to provide levels of 0% (control), 0.003%, 0.006% and 0.012% from 5 weeks of age of the F0 generation to 11 weeks of age of the F1 generation in mice. The exploratory behaviour of adult males in the F0 generation, the average time of movement, and the number of rearing and rearing time increased significantly in a dose-related manner in the Jonckheere test. The average speed increased in the middle- and high-dose groups, number of rearing increased in the high-dose group and rearing time lengthened in middle- and high-dose groups in the Shirley-Williams test. These results suggest that the use of the appropriate statistical methods adjusted to the objectives of the study and the characteristics of the data could provide more definite conclusions.

[Research progress on adverse reactions and pseudo-allergic reactions of traditional Chinese medicine injections].

Since the safety re-evaluation of traditional Chinese medicine(TCM) injections began in 2009, some TCM injection companies and research institutes have done a lot of work. And with the increase of drug development and drug production technology levels in China, the safety of some TCM injections has been greatly improved. There are safety risks in TCM injections, which are mainly reflected in unclear basis of medicinal materials, simple production process, poor controllability of quality standards, nonstan-dard drug instructions and irrational medication in the use process. This paper describes the research progress of the above-mentioned aspects of TCM injections. In addition, the author team found that adverse reactions of TCM injections are mainly pseudo-allergic reactions. Therefore, a lot of work has been done in detection of pseudo-allergic reactions, mechanism research and risk control. This part of the work is also described in this article.

Postmortem examination protocol and systematic re-evaluation reduce the proportion of unexplained stillbirths.

Background Stillbirth often remains unexplained, mostly due to a lack of any postmortem examination or one that is incomplete and misinterpreted. Methods This retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, Helsinki University Hospital, Finland, and comprised 214 antepartum singleton stillbirths from 2003 to 2015. Maternal and fetal characteristics and the results of the systematic postmortem examination protocol were collected from medical records. Causes of death were divided into 10 specific categories. Re-evaluation of the postmortem examination results followed. Results Based on our systematic protocol, the cause of death was originally defined and reported as such to parents in 133 (62.1%) cases. Re-evaluation of the postmortem examination results revealed the cause of death in an additional 43 (20.1%) cases, with only 23 (10.7%) cases remaining truly unexplained. The most common cause of stillbirth was placental insufficiency in 56 (26.2%) cases. A higher proportion of stillbirths that occurred at ≥39 gestational weeks remained unexplained compared to those that occurred earlier (24.1% vs. 8.6%) (P = 0.02). Conclusion A standardized postmortem examination and a re-evaluation of the results reduced the rate of unexplained stillbirth. Better knowledge of causes of death may have a major impact on the follow-up and outcome of subsequent pregnancies. Also, closer examination and better interpretation of postmortem findings is time-consuming but well worth the effort in order to provide better counseling for the grieving parents.

The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target.

The concept of leukaemic stem cells (LSCs) was experimentally suggested 25 years ago through seminal data from John Dick's group, who showed that a small fraction of cells from acute myeloid leukaemia (AML) patients were able to be adoptively transferred into immunodeficient mice. The initial estimation of the frequency was 1:250 000 leukaemic cells, clearly indicating the difficulties ahead in translating knowledge on LSCs to the clinical setting. However, the field has steadily grown in interest, expanse and importance, concomitantly with the realisation of the molecular background for AML culminating in the sequencing of hundreds of AML genomes. The literature is now ripe with contributions describing how different molecular aberrations are more or less specific for LSCs, as well as reports showing selectivity in targeting LSCs in comparison to normal haematopoietic stem and progenitor cells. However, we argue here that these important data have not yet been fully realised within the clinical setting. In this clinically focused review, we outline the difficulties in identifying and defining LSCs at the individual patient level, with special emphasis on intraclonal heterogeneity. In addition, we suggest areas of future focus in order to realise the concept as real-time benefit for AML patients.

Marked yield of re-evaluating phenotype and exome/target sequencing data in 33 individuals with intellectual disabilities.

The diagnosis of intellectual disability/developmental delay (ID/DD) benefits from the clinical application of target/exome sequencing. The yield in Mendelian diseases varies from 25% to 68%. The aim of the present study was to identify the genetic causes of 33 ID/DD patients using target/exome sequencing. Recent studies have demonstrated that reanalyzing undiagnosed exomes could yield additional diagnosis. Therefore, in addition to the normal data analysis, in this study, re-evaluation was performed prior to manuscript preparation after updating OMIM annotations, calling copy number variations (CNVs) and reviewing the current literature. Molecular diagnosis was obtained for 19/33 patients in the first round of analysis. Notably, five patients were diagnosed during the re-evaluation of the geno/phenotypic data. This study confirmed the utility of exome sequencing in the diagnosis of ID/DD. Furthermore, re-evaluation leads to a 15% improvement in diagnostic yield. Thus, to maximize the diagnostic yield of next-generation sequencing (NGS), periodical re-evaluation of the geno/phenotypic data of undiagnosed individuals is recommended by updating the OMIM annotation, applying new algorithms, reviewing the literature, sharing pheno/genotypic data, and re-contacting patients.

Influence of operator skill level on the clinical outcome of non-surgical periodontal treatment: a retrospective study.

OBJECTIVES: The aim of this study is to evaluate the effect of operators experience and skill on treatment results of initial non-surgical periodontal therapy. MATERIALS AND METHODS: Initial periodontal treatment was carried out by either second-year periodontal residents (PR) or last year dental students (DS). From the treatment records of patients in each group, plaque and bleeding indices, and pocket depth (PD) at baseline and at re-evaluation were collected retrospectively on each tooth at six locations. Data were separated according to tooth type, area, and probing depth categories, sub-grouped to 1-3, 4-5, and ≥ 6 mm. RESULTS: Fifty and 49 records of DS and PR patients, accordingly, were analyzed. Initial periodontal treatment improved patient compliance in both groups and reduced signs of inflammation with significantly superior results in the PR group. Significant change in percentage of pockets was recorded in each category. The increase in percentage of sites with PD 1-3 mm and decrease in percentage of PD ≥ 6 mm pockets was significantly (p ≤ 0.001) superior in patients treated by PR. Percentage of 4-5 mm pockets was significantly reduced in both groups (p ≤ 0.01), with a significantly greater reduction in the mandibular molar and anterior teeth in the PR group. CONCLUSIONS: Experience and skill significantly affect the outcome of non-surgical periodontal therapy, with more positive improvement in patient compliance and clinical parameters when performed by a more qualified operator. CLINICAL RELEVANCE: Improvement of operator skills may decrease the number of residual pockets and increase patient compliance following non-surgical periodontal treatment.

[Technical specification for re-evaluation of post-marketing clinical effectiveness of traditional Chinese medicine (first draft)].

The post-marketing re-evaluation of traditional Chinese medicine (TCM) is a crucial stage for drug evaluation. Due to the particularity of TCM, it is necessary to re-evaluate the effectiveness of certain Chinese medicines by studying and collecting the studies on safety of long-term/extensive populations under actual clinical application, in order to verify the effectiveness of post-marketing TCM. However, there is an absence in technical specifications for relevant clinical trials on re-evaluation of effectiveness at present. As a consequence, the preliminary technical specifications were drafted in this article, focusing on several perspectives related to the re-evaluation of post-marketing clinical effectiveness of TCM, including ethical protection, research plan formulation, real-world research methods, randomized controlled trial methods, research methods of clinical pharmacological mechanism, sublimation method of TCM theory and so on. The objective of writing this article is to provide general methodological guidance for the re-evaluation of TCM post-marketing effectiveness, so that the process and results of post-marketing re-evaluation of TCM can be more scientific and reasonable.

[Restraint in geriatric care, an overview]. / La contention en gériatrie, état des lieux.

Restraint is a deprivation of liberty which in certain, clearly codified situations is a necessary part of the care process. The multidisciplinary objective evaluation of the risk/benefit ratio must take into consideration the person's dignity. The situation is often encountered in geriatric care where the fundamental principles are the maintaining of autonomy or the functional improvement of the patient or resident.

Autochthonous human alveolar echinococcosis in a Hungarian patient.

BACKGROUND: Alveolar echinococcosis is a zoonotic parasitic disease causing a severe clinical condition and is known as the most deadly of all helminth infections. Moreover, this disease is also an increasing concern in Northern and Eastern Europe due to its spread in the wildlife animal host. CASE PRESENTATION: An asymptomatic 70-year-old woman from south-western Hungary was diagnosed with multiple liver lesions. Imaging techniques (ultrasound, computed tomography and magnetic resonance imaging), serology (ELISA, indirect hemagglutination and Western blot), and conventional staining methods (hematoxylin-eosin and periodic acid-Schiff) were used for the detection of the disease. A histopathological re-evaluation of formalin-fixed paraffin block by immunohistochemical staining with the monoclonal antibody Em2G11 definitively confirmed the diagnosis of alveolar echinococcosis. CONCLUSIONS: To our knowledge, this is the first confirmed autochthonous case of human alveolar echinococcosis in Hungary. To what extent diagnostic difficulties may contribute to underestimate this zoonosis in Eastern Europe is unknown. Differential diagnosis with alveolar echinococcosis should be considered for patients with multiple, tumor-like cystic lesions of the liver, in countries where this parasite is emerging.

[Post-marketing study on clinical safety of ginkgo diterpene lactone meglumine injection in 6 300 patients with ischemic stroke].

To further evaluate the safety of ginkgo diterpene lactone meglumine injection in the clinical use in ischemic stroke patients. Clinical safety study was conducted in 82 clinical units and 6 300 cases were completed and included from June 2013 to December 2014 by using multicenter, prospective, open and uncontrolled design methods for clinical research. A total of 29 cases of adverse reactions were observed in the experiment. Adverse reaction ratio (ADR) was 0.46%, and about 86.21% (25 cases) of them was mild with transient response which could be alleviated or disappeared without intervention; about 13.79% (4 cases) was moderate, including 2 cases of headache, 1 case of dizziness and 1 case of rash; no serious adverse reactions were found. The adverse reactions occurred in this study were pre-known adverse reactions or common adverse reactions of Chinese medicine injection. The overall incidence of adverse reactions was low, and the risk was controllable.

Evaluation of rational extent lymphadenectomy for local advanced gastric cancer.

Based upon studies from randomized clinical trials, the extended (D2) lymph node dissection is now recommended as a standard procedure for local advanced gastric cancer worldwide. However, the rational extent lymphadenectomy for local advanced gastric cancer has remained a topic of debate in the past decades. Due to the limitation of low metastatic rate in para-aortic nodes (PAN) in JCOG9501, the clinical benefit of D2+ para-aortic nodal dissection (PAND) for patients with stage T4 and/or stage N3 disease, which is very common in China and other countries except Japan and Korea, cannot be determined. Furthermore, the role of splenectomy for complete resection of No.10 and No.11 nodes has been controversial, and however, the final results from the randomized trial of JCOG0110 have yet to be completed. Gastric cancer with the No.14 and No.13 lymph node metastasis is defined as M1 stage in the current version of the Japanese classification. We propose that D2+No.14v and +No.13 lymphadenectomy may be an option in a potentially curative gastrectomy for tumors with apparent metastasis to the No.6 nodes or infiltrate to duodenum. The examined lymph node and extranodal metastasis are significantly associated with the survival of gastric cancer patients.

Feasibility re-evaluation of 75 mg/m² docetaxel in Japanese patients with previously treated non-small cell lung cancer.

OBJECTIVE: The primary objective of this study was to re-evaluate the feasibility of docetaxel at doses of up to 75 mg/m² in Japanese patients with previously treated non-small cell lung cancer. METHODS: Patients received escalated doses of docetaxel at 70 mg/m² (level 1) or 75 mg/m² (level 2) every 3 weeks until disease progression or unacceptable toxicities. Dose escalation was decided on the basis of dose-limiting toxicity in the first cycle of chemotherapy. RESULTS: At dose level 1, dose-limiting toxicity--Grade 3 febrile neutropenia--was observed in one of the six patients and at dose level 2, it was seen in one of the first six patients. Therefore, an additional 14 patients were enrolled at dose level 2, as originally planned. Among the total of 20 patients at dose level 2, 6 (<33%) developed dose-limiting toxicity in the first cycle: febrile neutropenia in 5 and pneumonia in 1. Finally, 10 (50%) of the 20 patients experienced toxicities that met the dose-limiting toxicity criteria, including 8 with febrile neutropenia throughout the treatment period, but this was manageable with dose reduction or appropriate supportive care. Other observed toxicities were predictable from the safety profile of decetaxel and were also well managed. Four partial responses were observed, giving an overall response rate of 15.4%. The median progression-free survival period of the patients overall was 4.0 months (95% confidence interval 1.4-6.6 months). CONCLUSIONS: Although docetaxel administration at an initial dose of 75 mg/m² requires careful attention because of the high incidence of febrile neutropenia, this dose is considered feasible according to the protocol definition in Japanese patients with previously treated non-small cell lung cancer.

Can face recognition be selectively preserved in some cases of amnesia? A cautionary tale.

Evidence suggests that some patients with isolated hippocampal damage appear to present with selective preservation of unfamiliar face recognition relative to other kinds of visual test stimuli (e.g., words). Bird and Burgess (2008) formulated a review and secondary analysis of a group of 10 cases all tested on a clinical assessment of word and face recognition memory (RMT, Warrington, 1984), which confirmed the key memory dissociation at the group level. The current work provides an updated secondary analysis of such cases with a larger published sample (N = 52). In addition to group-level analyses, we also re-evaluate evidence using a single case statistical approach (Crawford & Garthwaite, 2005), enabling us to determine how many would make criteria for a 'classical dissociation' (Crawford, Garthwaite, & Gray, 2003). Overall, group-level analyses indicated the key pattern of significant differences confined to words was limited to small control sample comparisons. When using the large control sample provided by Bird and Burgess (2008), hippocampal cases as a group were significantly poorer for both classes of items. Furthermore, our single-case approach indicated few had a performance pattern of a relative difference across face > word categories that would meet statistical significance; namely within individual differences across categories that would warrant a significant 'classical dissociation'. Moreover, these analyses also found several cases with a 'classical dissociation' in the reverse direction: namely preserved recognition of words. Such analyses serve to demonstrate the need for a more conservative statistical approach to be undertaken when reporting selective 'preservation' of a category in recognition memory. Whilst material specificity has important implications for understanding the role of the hippocampus in memory, our results highlight the need for statistical methods to be unquestionably rigorous before any claims are made. Lastly, we highlight other methodological issues critical to group analyses and make suggestions for future work.

Re-evaluation and operative indications after induction therapy for thymic epithelial tumors.

Thymic epithelial tumors (TETs), encompassing thymoma and thymic carcinoma, represent a rare and heterogeneous group of thoracic malignancies with varying prognoses and treatment strategies. Surgical resection is the cornerstone of therapy for localized stages, but the management of locally advanced or unresectable TETs often involves induction therapy, including chemotherapy and/or radiation therapy, as a neoadjuvant approach aimed at downstaging the tumor to facilitate subsequent resection. This review synthesizes current knowledge on the re-evaluation process and operative indications following induction therapy for TETs, highlighting the pivotal role of accurate assessment in guiding surgical decisions and optimizing patient outcomes. Induction therapy's efficacy is contingent upon precise re-evaluation methods to accurately gauge treatment response and assess resectability post-therapy. This review discusses the various modalities employed in re-evaluation, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT), and the significance of tumor markers, underlining their strengths and limitations. The adoption of modified RECIST criteria for TETs by the International Thymic Malignancy Interest Group (ITMIG) underscores the necessity for standardized assessment guidelines to ensure consistency and reliability across studies and clinical practices. Furthermore, we explore the implications of induction therapy on surgical decision-making, emphasizing the criteria for determining the suitability of patients for surgical intervention post-therapy. The review addresses the challenges and future perspectives associated with the re-evaluation process, including the potential for advanced imaging techniques and the integration of molecular and genetic markers to enhance the precision of treatment response assessment. In conclusion, the re-evaluation of TETs post-induction therapy is a complex but critical component of the multidisciplinary management approach for these patients. Standardizing re-evaluation methodologies and incorporating novel diagnostic tools could significantly improve the prognostication and treatment stratification, ultimately enhancing the therapeutic outcomes for patients with advanced TETs.

The safety and effectiveness of music medicine as an intervention for depression: A systematic evaluation and re-evaluation.

BACKGROUND: As the methodological quality and evidence level of the existing systematic reviews (SRs) on music as an intervention for depression have not been thoroughly evaluated, a systematic evaluation and re-evaluation (SERE) was conducted. METHODS: Multiple databases including PubMed, Web of Science, Embase, China National Knowledge Infrastructure, SinoMed, Wanfang, and the VIP database were searched for SRs and meta-analyses (MAs) on the effectiveness of music as an intervention for depression. The literature screening, evaluation of methodological quality, and assessment of evidence level were carried out by a team of researchers. The methodological quality was evaluated using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) scale in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria were utilized to assess the level of evidence. RESULTS: A total of 18 SRs were included in the analysis. The 2020 PRISMA guidelines were utilized to evaluate various aspects such as search terms, funding sources, statistical methods for missing values, subgroup and sensitivity analyses, certainty assessment, excluded literature citations, assessment of publication bias, protocol information, conflicts of interest, and data availability, which were rarely reported. The evaluation of the studies using the AMSTAR 2 scale revealed that one article was rated as high quality, six were rated as low quality, and 11 were rated as very low quality. Based on the GRADE criteria evaluation, the quality of the evidence was found to be inconsistent, with reports primarily consisting of medium-quality evidence. CONCLUSION: The methodological quality of SRs/MAs of music as an intervention in depression is generally poor, and the level of evidence is generally low.

Compound heterozygous mutations in three Chinese patients of Segawa syndrome and their treatment outcomes.

Segawa syndrome is a rare autosomal recessive form of dopa-responsive dystonia resulting from TH gene dysfunction. Patients typically exhibit symptoms such as generalized dystonia, rigidity, tremors, infantile Parkinsonism, and pseudo-spastic paraplegia. Levodopa is often an effective treatment. Due to its rarity, high heterogeneity, and poorly understood pathological mutation and phenotype spectrums, as well as genotype-phenotype and genotype-treatment outcome correlations, Segawa syndrome poses diagnostic and therapeutic challenges. In our study, through clinical and molecular analyses of three Chinese Segawa patients, we re-evaluated the pathogenicity of a TH mutation (c.880G>C;p.G294R) previously categorized as "Conflicting classifications of pathogenicity" in ClinVar. Also, we summarized the clinical phenotypes of all reported Segawa syndrome cases until 2023 and compared them with our patients. We identified a novel phenotype, "cafe-au-lait macules," not previously observed in Segawa patients. Additionally, we discussed the correlation between specific genotypes and phenotypes, as well as genotypes and treatment outcomes of our three cases. Our findings aim to enhance the understanding of Segawa syndrome, contributing to improved diagnosis and treatment approaches in the future.