PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.

BACKGROUND: The diagnosis and treatment of fibro-adipose vascular anomaly (FAVA) of the limb remains challenging since this entity is rare and complex. This paper is aimed to describe the clinical and imaging features, staging and management of this underrecognized disease of the limb.
METHODS: Patients diagnosed with FAVA and managed between September 2019 and May 2022 in department of pediatric surgery & vascular anomalies of Xi\'an international medical center hospital were retrospectively reviewed. Data extracted include age at presentation, previous diagnosis, affected muscles, symptoms, previous treatment, our management, and follow-up.
RESULTS: Thirty-two patients with FAVA were diagnosed and managed in our center. There was a female sex predominance, with 23 female (72%) and 9 male (28%) in the cohort. Only one lesion was noticed during infancy; the remaining presented at age 1 to 20 years (median, 7 years). The most commonly involved muscles were gastrocnemius (14/32, 44%) and soleus (13/32, 40%). Swelling (mass), pain and contractures were the most common presentations. MRI featured a heterogeneous and ill-defined intramuscular high signal intensity. Diseases were staged according to clinical features: stage I (pain stage, n = 4), stage II (contracture stage, n = 20) and stage III (deformity stage, n = 8). Patients with stage I disease underwent radical resection and obtained a cure. Patients with stage II disease received radical resection and possible Achilles lengthening, having an outcome of cure. Personalized treatment was required in patients with stage III disease, including radical/partial/staged resection, Achilles lengthening/tenotomy, joint capsulotomy, neurolysis/neurectomy, tendon transfer, stretching exercises, and oral sirolimus/alpelisib. Significant improvement of symptoms was achieved in most.
CONCLUSIONS: The most distinct features of FAVA include enlarging mass, severe pain and contracture. Based on distinct clinical and radiologic features, it is not difficult to make the diagnosis of FAVA. Earlier awareness of this disease can reduce misdiagnoses. Surgery-based comprehensive management can typically improve pain and contracture. Oral sirolimus or alpelisib plays an important role in treatment of unresectable lesions and major nerve involvement. Surgery alone can be curative in early stage FAVA.

UNASSIGNED: Patient-reported outcomes (PROs) are increasingly becoming an important part of clinical trials as they are helpful in analyzing the safety and efficacy of treatment in chronic diseases like cancer.
UNASSIGNED: We report PROs and health-related quality of life (HRQoL) with selpercatinib treatment among Chinese patients with rearranged in transfection (RET) fusion-positive non-small-cell lung cancer (NSCLC), RET fusion-positive thyroid cancer (TC), and RET-mutant medullary TC (MTC) as an exploratory analysis of the LIBRETTO-321 trial.
UNASSIGNED: A total of 77 patients (47 RET fusion-positive NSCLC, 1 RET fusion-positive TC, and 29 RET-mutant MTC) were enrolled. Compliance for European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) was 100% at baseline and >90% at each time point.
UNASSIGNED: PROs were assessed using the EORTC QLQ-C30, and a bowel diary assessment for MTC patients with baseline diarrhea using the Systemic Therapy-Induced Diarrhea Assessment Tool. Data were collected at pre-dose; every 8 weeks from cycle 3; and every 12 weeks after cycle 13. A >10-point change from baseline was considered clinically meaningful. PRO changes were summarized through cycle 13.
UNASSIGNED: Most patients with NSCLC or MTC showed improvement or remained stable on the global health status and functional subscales. For global health status, 47.4% of NSCLC and MTC patients showed definite improvement with only 19.7% showing definite worsening. For functional subscales, less than 30% of the patients showed definite worsening. For symptom subscales, more than 64% of the patients either improved or remained stable for the symptoms. For MTC patients with bowel diary assessment (n = 5), there was no severity or worsening from baseline in the diarrheal episodes observed during treatment with selpercatinib.
UNASSIGNED: The study demonstrated favorable PROs in Chinese patients with RET fusion-positive NSCLC, TC, and RET-mutant MTC treated with selpercatinib. HRQoL was improved or stable as assessed by EORTC QLQ-30.
UNASSIGNED: This study was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04280081) ClinicalTrials.gov Identifier: NCT04280081.

OBJECTIVE: This review aimed to determine how successful aging is operationalized in the oral heath context, and to determine the use of Patient Reported Outcomes (PROs) and Dental Patient Reported Outcomes (dPROs).
METHODS: A scoping review was conducted and was registered with PROSPERO (CRD42021232668). The reporting of the review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework.
RESULTS: Five databases were searched and 1288 potentially relevant publications were identified. A total of 263 \'effective\' studies informed this review. Most studies were observational in nature (94.3%, 250) and the majority were cross-sectional (52.5%, 139). Most studies (89.4%, 235) were unidimensional in their operationalization of successful aging. Successful aging was mainly operationalized in terms of the \'biomedical model\' (81.4%, 214) with limited consideration of psychological and social dimensions/models. Regarding biological health, commonly considered components were \'nutrition\' (33.6%, 72/214) and \'longevity\' (28.9%, 62/214). PROs were most frequently employed in the assessment of nutrition (88.8%, 64/72), albeit in response to standardized assessments. Regarding the psychological dimension (28.9%, 76), \'cognition\' was most frequently assessed (69.7%, 53/76) - typically by the use of PROs (83.0%, 44/53). Social dimensions were only rarely considered (1.5%, 4). In terms of oral health - a range of aspects were considered including: \'number of teeth\' (58.2%, 153 - dPROs (31.6%, 49/155)); and prosthesis use (30.4%, 80 - dPROS (31.3%, 25/80)).
CONCLUSIONS: The operationalization of successful aging in oral health is typically unidimensional and focuses primarily on the \'biomedical model\'. PROs and dPROS are both widely used in the assessment of successful aging in the oral health context.

BACKGROUND: Mental retardation is a complex neurodevelopmental disorder. NPAT, a component of the histone locus body (HLB), has been implicated as a candidate gene for mental retardation, with a mechanism yet to be elucidated.
RESULTS: We identified that mxc, the Drosophila ortholog of NPAT, is required for the development of nervous system. Knockdown of mxc resulted in a massive loss of neurons and locomotion dysfunction in adult flies. In the mxc mutant or RNAi knockdown larval brains, the neuroblast (NB, also known as neural stem cell) cell fate is prematurely terminated and its proliferation potential is impeded concurrent with the blocking of the differentiation process of ganglion mother cells (GMCs). A reduction of transcription levels of histone genes was shown in mxc knockdown larval brains, accompanied by DNA double-strand breaks (DSBs). The subsidence of histone transcription levels leads to prematurely termination of NB cell fate and blockage of the GMC differentiation process. Our data also show that the increase in autophagy induced by mxc knockdown in NBs could be a defense mechanism in response to abnormal HLB assembly and premature termination of NB cell fate.
CONCLUSIONS: Our study demonstrate that Mxc plays a critical role in maintaining neural stem cell fate and GMC differentiation in the Drosophila larval brain. This discovery may shed light on the understanding of the pathogenesis of NPAT-related mental retardation in humans.

BACKGROUND: There has been a delay in the detection and treatment of lymphedema in breast cancer patients during the lockdown owing to quarantine and limited social activity. Moreover, this scenario has caused psychosocial issues in these patients. Given that there is scarce information on the prevalence and influence of lymphedema during the coronavirus disease (COVID-19) pandemic, we aimed to estimate the prevalence of lymphedema recurrence and its influencing factors among discharged breast cancer patients during the COVID-19 pandemic.
METHODS: This was a multicenter, cross-sectional, hospital-based survey of discharged breast cancer patients was conducted during the COVID-19 pandemic in eight first-class hospitals in Wuhan, China. The Norman Questionnaire was used to assess lymphedema. Univariable and multivariable binary logistic regression analyses were performed to identify factors influencing moderate or severe lymphedema. Differences in living characteristics, anxiety, and depression were compared between the no/mild lymphedema group and the moderate/severe lymphedema groups. Preferences for lymphedema management during the pandemic were determined.
RESULTS: Overall, 202 patients were included in this study, and 191 of them reported recurrent lymphedema (prevalence: 94.6%, 95% confidence interval [CI] 90.5% to 97.3%). Among them, 134 and 57 had mild and moderate/severe lymphedema, respectively. In 191 patients, the main symptoms were swelling (140; 69.3%) and pain (56, 27.7%). Multivariable regression showed that older age (odds ratio [OR], 1.06; 95% CI: 1.02-1.10), radical surgery (OR = 4.35, 95% CI: 1.54-12.50), and fully complete radiotherapy (OR = 2.62, 95% CI: 1.17-5.87, p = 0.019) were associated with an elevated risk of moderate/severe lymphedema. The moderate/severe lymphedema group experienced a higher rate of anxiety and depression than the no/mild lymphedema group did. Patients equally preferred treatment in the hospital and self-care at home.
CONCLUSIONS: During the COVID-19 pandemic, high prevalence of lymphedema was observed in patients Age, radical surgery and fully completed radiotherapy were associated with increased risk of severer lymphedema. Meanwhile, the patients with severe lymphedema experienced psychological distress. While the Covid-19 pandemic was still raging, continuous efforts should be made to identify patient at risk of lymphedema and distribute feasible guidance and education for self-management in lymphedema.

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PIK3CA-related overgrowth spectrum (PROS) is a series of congenital, sporadic disorders that are associated with segmental overgrowth phenotypes and postzygotic, somatic gene mutations in the PIK3CA-ATK-mTOR pathway. The variability and overlapping phenotypes between PROS and other complex vascular malformations make the differential diagnosis confusing and challenging. PROS should be considered for the differential diagnosis with other complex vascular malformations and syndromes with a tissue overgrowth phenotype, such as Parkes-Weber syndrome (PWS).Herein, we diagnosed one unique clinically challenging case manifested as capillary malformation (CM), limb overgrowth, as well as increased skin temperature and peripheral venous dilatation of lower limb that indicated a potential fast-flow lesion. The patient was initially diagnosed with PWS. Contrary to the previous diagnosis, based on further MR imaging and digital subtraction angiography (DSA), which ruled out the existence of AVMs and AVFs, and molecular analysis with targeted next-generation sequencing (NGS) revealing a somatic PIK3CA mutation, we ultimately diagnosed that the patient had a unique form of PROS simulating PWS phenotypes. We suggest that it is important to propose the differential diagnosis of PWS and PROS, two diseases that share a common overgrowth phenotype. We recommended radiological diagnosis such as MRI, CT and DSA as well as further molecular diagnosis to provide more information for the assessment of vascular lesions and to further guide clinical treatment strategies.

Late-onset Pompe Disease (LOPD) is a rare, heterogeneous disease manifested by a range of symptoms varying in severity. Research establishing the frequency of these symptoms and their impact on patients\' daily lives is limited. The objective of this study was to develop a conceptual model that captures the most relevant symptoms and functional limitations experienced by patients with LOPD, to inform the development of new patient-reported outcome (PRO) tools.
A preliminary conceptual model was constructed following a literature review and revised through interviews with expert clinicians to identify important and relevant concepts regarding symptoms and impacts of LOPD. This preliminary model informed the development of a qualitative patient interview guide, which was used to gather the patient perspective on symptoms and impacts relating to LOPD or its treatment (including symptom/impact frequency and levels of disturbance). Patient interviews aided further refinement of the conceptual model. The findings from the patient interviews were triangulated with the literature review and clinician interviews to identify the most relevant and significant effects of LOPD from the patient perspective.
Muscle weakness, fatigue, pain, and breathing difficulties (especially while lying down) were the most common and highly disturbing symptoms experienced by patients. Limitations associated with mobility (e.g., difficulty rising from a sitting position, getting up after bending) and activities of daily living, (e.g., reduced ability to participate in social/family activities or work/study) were the most frequently reported impacts with the highest levels of disturbance on the patient\'s daily life. These identified symptoms and impacts were included in the new conceptual model of disease.
This qualitative patient interview study, also informed by a literature review and clinician interviews, identified the most frequent and relevant symptoms and the functional impact of LOPD on patients. The study interviews also captured the patient-preferred language to describe symptoms and impacts of LOPD. The results from this study can be used to develop future PRO instruments that are tailored to the specific symptoms and impacts experienced by patients with LOPD.

BACKGROUND: Antithrombin (AT) deficiency is associated with an increasing risk of thrombosis.
METHODS: 15 unrelated patients with AT deficiency defined by thrombophilic assays were recruited and detailed clinical information about patients, focusing on the personal and family history of thromboembolism (TE), were recorded. Mutation analysis was performed by direct sequencing of an AT gene (SERPINC1) in the patients and their family members.
RESULTS: A total of 15 heterozygous causative mutations, each being identified in one family, were identified. Five mutations (33.3%) were reported here for the first time, including three null mutations (Ser36X, Lys70X and Try307X) and two missense mutations (Phe123Cys and Leu340Phe) probably impairing the structural integrity and stability of protein based on the AT structural analysis. Of the 15 patients, 33.3% (5/15) had additional risk factors and only one patient presented with additional genetic alteration causing an early onset of thrombosis. Fourteen patients (93.9%) suffered from multisite recurrent thrombotic episodes after a first episode of thrombosis. 93.3% of the patients experienced deep vein thrombosis (DVT) and 40.0% presented with mesenteric venous thrombosis (MVT). In addition, both venous and arterial thrombosis was present in two unrelated patients. 51.0% subjects with AT deficiency in the 15 unrelated pedigrees experienced TE events.
CONCLUSIONS: Prophylactic anticoagulation may be suggested in AT-deficient patients to avoid the recurrent and multisite thrombosis. The association of primary MVT and AT deficiency is highlighted.