Clinical characteristics and surgical management of facial infiltrating lipomatosis: a single center experience.

BACKGROUND: Facial infiltrating lipomatosis (FIL) is a rare condition characterized by congenital facial enlargement. Beyond its impact on physical appearance, FIL can also impair essential facial functions such as swallowing, chewing, vision, and breathing, imposing a substantial physiological and psychological burden. Currently, fewer than 80 cases of FIL have been reported, and the characteristics and management strategies for FIL remain unclear. METHODS: We reviewed the clinical, surgical, and radiological records of 39 FIL patients who were treated at our center. Of these, genetic testing was performed for 21 patients. RESULTS: Aberrant overgrowth involves subcutaneous fat, bones, muscles, glands, tongue, lips, and teeth. Epidermal nevi could be observed in the dermatomes innervated by the three branches of the trigeminal nerve, with the highest frequency seen in the dermatome of the mandibular branch. Four patients exhibited concurrent hemimegalencephaly (HMEG), with one case presenting HMEG on the opposite side of the FIL. Nineteen patients were confirmed to harbor the PIK3CA mutation. Thirty-three patients underwent surgical procedures, with a post resection recurrence rate of approximately 25%. CONCLUSIONS: A variety of maxillofacial structures may be involved in FIL. PIK3CA mutations are important pathogenic factors. Emerging targeted therapies could present an additional treatment avenue in the future. However, surgery currently remains the predominant treatment choice for FIL. The timing and modality of surgery should be individually customized, taking into account each patient's unique circumstances. Notably, there is a significant possibility of postoperative recurrence during childhood and adolescence, necessitating early strategic planning of disease management.

Delineation of the phenotypes and genotypes of facial infiltrating lipomatosis associated with PIK3CA mutations.

BACKGROUND: Facial infiltrating lipomatosis (FIL) is a rare congenital disorder characterized by unilateral facial swelling, for which surgery is the prevailing therapeutic option. Several studies have shown that the development of FIL is closely associated with PIK3CA mutations. This study aimed to further identify rare clinical features and underlying molecular variants in patients with FIL. RESULTS: Eighteen patients were included in this study, and all patients presented with infiltrating adipose tissues confirmed by magnetic resonance imaging. Macrodactyly, polydactyly, hemimegalencephaly and hemihyperplasia were also observed in patients with FIL. In total, eight different PIK3CA mutations were detected in tissues obtained from sixteen patients, including the missense mutations p.His1047Arg (n = 4), p.Cys420Arg (n = 2), p.Glu453Lys (n = 2), p.Glu542Lys (n = 2), p.Glu418Lys (n = 1), p.Glu545Lys (n = 1), and p.His1047Tyr (n = 1) and the deletion mutation p.Glu110del (n = 3). Furthermore, the GNAQ mutation p.Arg183Gln was detected in the epidermal nevus tissue of one patient. Imaging revealed that several patients carrying hotspot mutations had more severe adipose infiltration and skeletal deformities. CONCLUSIONS: The abundant clinical presentations and genetic profiles of FIL make it difficult to treat. PIK3CA mutations drive the pathogenesis of FIL, and PIK3CA hotspot mutations may lead to more extensive infiltration of lipomatosis. Understanding the molecular variant profile of FIL will facilitate the application of novel PI3K-targeted inhibitors.

Facial infiltrating lipomatosis with hemimegalencephaly and lymphatic malformations caused by nonhotspot phosphatidylinositol 3-kinase catalytic subunit alpha mutation.

We report an unusual case of facial infiltrating lipomatosis with hemimegalencephaly and lymphatic malformations. In addition to the clinical data and imaging findings, detection of a heterozygous PIK3CA nonhotspot known pathogenic variant C420R in a facial epidermal nevus provided novel insight into the pathogenic effect of somatic PIK3CA mutations.

Chest tube-free video-assisted thoracoscopic surgery secured by quantitative air leak monitoring: a case series.

Background: Although chest tube-omitted video-assisted thoracoscopic surgery (VATS) has been proven to be safe and efficacious, its universal application is precluded by a varying morbidity rate due to a lack of standardization. Since digital chest drainage has already shown improved accuracy and consistency in the management of postoperative air leak, we incorporated it in the strategy of intraoperative chest tube withdrawal, aiming to achieve better results. Methods: We collected the clinical data of 114 consecutive patients who underwent elective uniportal VATS pulmonary wedge resection at the Shanghai Pulmonary Hospital from May 2021 to February 2022. Their chest tubes were withdrawn intraoperatively after an air-tightness test facilitated by digital drainage: the end flow rate had to be kept ≤30 mL/min for >15 s at the setting of -8 cmH2O suctioning. The recordings and patterns of the air suctioning process were documented and analyzed as potential standards of chest tube withdrawal. Results: The mean age of the patients was 49.7±11.7 years. The mean size of the nodules was 1.0±0.2 cm. The location of the nodules encompassed all lobes, and 90 (78.9%) patients received preoperative localization. The postoperative morbidity and mortality rates were 7.0% and 0%, respectively. Six patients had clinically overt pneumothorax and two patients had postoperative bleeding that required intervention. All of the patients recovered on conservative treatment except for one case of pneumothorax that required additional tube thoracostomy. The median length of postoperative stay was 2 days; and the median time of suctioning, peak flow rate, and end flow rate were 126 s, 210 mL/min, and 0 mL/min, respectively. The median numeric rating scale for pain was 1 on postoperative day (POD) 1 and 0 on the day of discharge. Conclusions: Chest tube-free VATS assisted by digital drainage is feasible with minimal morbidity. Its strength of quantitative air leak monitoring produces important measurements for the prediction of postoperative pneumothorax and future standardization of the procedure.

Updates on Diagnosis and Treatment of PIK3CA-Related Overgrowth Spectrum.

ABSTRACT: Hyperactivation of the PI3K/AKT/mTOR signaling pathway caused by PIK3CA mutations is associated with a category of overgrowth syndromes that are defined as PIK3CA -related overgrowth spectrum (PROS). The clinical features of PROS are highly heterogeneous and usually present as vascular malformations, bone and soft tissue overgrowth, and neurological and visceral abnormalities. Detection of PIK3CA variants is necessary for diagnosis and provides the basis for targeted therapy for PROS. Drugs that inhibit the PI3K pathway offer alternatives to conventional therapies. This article reviews the current knowledge of PROS and summarizes the latest progress in precise treatment, providing new insights into future therapies and research goals.

Protection against Doxorubicin-Related Cardiotoxicity by Jaceosidin Involves the Sirt1 Signaling Pathway.

The clinical use of doxorubicin (DOX) is largely limited by its cardiotoxicity. Previous studies have shown that jaceosidin has many biological activities. However, little is known about whether jaceosidin can attenuate DOX-related acute cardiotoxicity. Here, we investigated the therapeutic effects of jaceosidin on DOX-induced acute cardiotoxicity. Mice were intraperitoneally injected with a single dose of DOX to establish an acute cardiac injury model. To explore the protective effects, mice were orally administered jaceosidin daily for 7 days, with dosing beginning 2 days before DOX injection. The results demonstrated that jaceosidin dose-dependently reduced free radical generation, inflammation accumulation, and cell loss induced by DOX in cardiomyocytes. Further studies showed that jaceosidin treatment inhibited myocardial oxidative damage and the inflammatory response and attenuated myocardial apoptotic death, thus improving cardiac function in mice injected with DOX. The inhibitory effects of jaceosidin on DOX-related acute cardiotoxicity were mediated by activation of the sirtuin1 (Sirt1) signaling pathway. Jaceosidin lost its protective effect against DOX-related injury in Sirt1-deficient cardiomyocytes and mice. In conclusion, jaceosidin has protective potential in treating DOX-related cardiac injury through activation of the Sirt1 signaling pathway.

C1qTNF-related protein 1 attenuates doxorubicin-induced cardiac injury via activation of AKT.

AIMS: The clinical use of doxorubicin (Dox) is limited due to a degenerative irreversible cardiac toxicity, but the precise mechanisms that contribute to this pathological response are not understood. C1q/TNF-related protein 1 (CTRP1), which is a conserved protein of the C1q family, has notable metabolic and cardiovascular functions. However, whether CTRP1 can attenuate Dox-induced cardiac injury remains unclear. Our study aimed to investigate the effect of CTRP1 on Dox-induced cardiotoxicity and assessed the mechanisms of this effect. MATERIALS AND METHODS: We manipulated CTRP1 expression in the heart using in vivo gene delivery system. Two weeks after gene delivery, the mice received a single intraperitoneal injection of Dox (20 mg/kg) to induce cardiac injury. KEY FINDINGS: Cardiac CTRP1 protein levels were decreased in DOX-treated mice. CTRP1 overexpression reduced plasma cardiac troponin I, restored cardiac function and attenuated cardiomyocyte apoptosis in Dox-treated mice. CTRP1 also improved cell viability and reduced lactate dehydrogenase release in vitro. Dox resulted in the decreased the protein kinase B (PKB/AKT) phosphorylation, which were restored by CTRP1 overexpression. AKT inhibition offset the inhibitory effects of CTRP1 on myocyte apoptosis in vitro. CTRP1 lost its protection against Dox-induced cardiac injury in mice with AKT deficiency. Furthermore, infusion of recombinant CTRP1 protein could reverse pre-established injury in heart induced by Dox treatment. SIGNIFICANCE: In conclusion, CTRP1 protected against Dox-induced cardiotoxicity via activation of AKT. CTRP1 has the therapeutic potential to treat Dox-induced cardiotoxicity.