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1.
Blood ; 139(11): 1619-1630, 2022 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-35030255

RESUMEN

The Kasabach-Merritt phenomenon (KMP) in kaposiform hemangioendothelioma (KHE) is characterized by life-threatening thrombocytopenia and consumptive coagulopathy. This study compared the efficacy and safety of sirolimus plus prednisolone vs sirolimus monotherapy as treatment strategies for KHE with KMP in the largest cohort to date. Participants were randomized to receive either sirolimus in combination with a short course of prednisolone or sirolimus monotherapy for at least 12 months. The primary outcome was defined as achievement of a durable platelet response (platelet count >100 × 109/L) at week 4. Participants completed efficacy assessments 2 years after the initial treatment. At week 4, a durable platelet response was achieved by 35 of 37 patients given sirolimus and prednisolone compared with 24 of 36 patients given sirolimus monotherapy (difference 27.9%; 95% confidence interval, 10.0-44.7). Compared with the sirolimus monotherapy group, the combination treatment group showed improvements in terms of measures of durable platelet responses at all points during the initial 3-week treatment period, median platelet counts during weeks 1 to 4, increased numbers of patients achieving fibrinogen stabilization at week 4, and objective lesion responses at month 12. Patients receiving combination therapy had fewer blood transfusions and a lower total incidence of disease sequelae than patients receiving sirolimus alone. The frequencies of total adverse events and grade 3-4 adverse events during treatment were similar in both groups. The responses seen in patients with KHE with KMP were profound and encouraging, suggesting that sirolimus plus prednisolone should be considered a valid treatment of KHE with KMP. This trial was registered at www.clinicaltrials.gov as #NCT03188068.


Asunto(s)
Hemangioendotelioma , Síndrome de Kasabach-Merritt , Sarcoma de Kaposi , Hemangioendotelioma/complicaciones , Hemangioendotelioma/tratamiento farmacológico , Hemangioendotelioma/patología , Humanos , Lactante , Síndrome de Kasabach-Merritt/complicaciones , Síndrome de Kasabach-Merritt/tratamiento farmacológico , Síndrome de Kasabach-Merritt/patología , Prednisolona/uso terapéutico , Sarcoma de Kaposi/complicaciones , Sirolimus/uso terapéutico
2.
Int J Cancer ; 153(3): 600-608, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36916140

RESUMEN

Treatment with sirolimus, an inhibitor of the mammalian target of rapamycin pathway, has improved the prognosis of patients with kaposiform hemangioendothelioma (KHE). However, the efficacy, durability and tolerability of long-term sirolimus treatment in patients with KHE have not been well elucidated. We performed efficacy and safety assessments based on more than 4.5 years of follow-up in patients receiving sirolimus therapy for KHE. One hundred sixty-seven patients were analyzed, including 102 (61.1%) patients with the Kasabach-Merritt phenomenon (KMP). Follow-up was conducted after a median of 56.0 months. A total of 154 (92.2%) patients had a durable response to sirolimus treatment. No difference in durable response was found between patients without KMP and patients with KMP (95.4% vs 90.2%; difference, 5.2%; 95% confidence interval [CI], -4.0% to 13.1%). Rebound growth occurred in 17.3% of patients upon sirolimus discontinuation. Early treatment discontinuation (odds ratio [OR]: 3.103; 95% CI: 1.529-6.299; P = .002) and mixed lesion type (OR: 2.271; 95% CI: 0.901-5.727; P = .047) were associated with tumor rebound growth. No KHE-related deaths occurred in this cohort. At the last follow-up, approximately 17.4% of patients had active disease and/or changes in body structures to a variable extent. Serious adverse events occurred most commonly during the first year of sirolimus therapy. Follow-up of almost 4.5 years demonstrated that the efficacy of sirolimus persisted over time and that long-term treatment with sirolimus was not associated with unacceptable cumulative toxicities. However, nonresponse, tumor relapse and long-term sequelae remained challenges despite intensified and prolonged sirolimus therapy.


Asunto(s)
Hemangioendotelioma , Síndrome de Kasabach-Merritt , Sarcoma de Kaposi , Humanos , Síndrome de Kasabach-Merritt/tratamiento farmacológico , Sirolimus/efectos adversos , Hemangioendotelioma/tratamiento farmacológico , Sarcoma de Kaposi/tratamiento farmacológico
3.
J Transl Med ; 21(1): 85, 2023 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-36740704

RESUMEN

BACKGROUND: Infantile hemangioma (IH) is the most common tumor among infants, but the exact pathogenesis of IH is largely unknown. Our previous study revealed that glucose metabolism may play an important role in the pathogenesis of IH and that the inhibition of the glycolytic key enzyme phosphofructokinase-1 suppresses angiogenesis in IH. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a metabolic enzyme that converts fructose-6-bisphosphate to fructose-2,6-bisphosphate (F-2,6-BP), which is the most potent allosteric activator of the rate-limiting enzyme phosphofructokinase-1. This study was performed to explore the role of PFKFB3 in IH. METHODS: Microarray analysis was performed to screen the differentially expressed genes (DEGs) between proliferating and involuting IH tissues. PFKFB3 expression was examined by western blot and immunohistochemistry analyses. Cell migration, apoptosis and tube formation were analyzed. Metabolic analyses were performed to investigate the effect of PFKFB3 inhibition by PFK15. Mouse models were established to examine the effect of PFKFB3 inhibition in vivo. RESULTS: PFKFB3 was identified as one of the most significant DEGs and was more highly expressed in proliferating IH tissues and hemangioma-derived endothelial cells (HemECs) than in involuting IH tissues and human umbilical vein endothelial cells, respectively. PFKFB3 inhibition by PFK15 suppressed HemEC glucose metabolism mainly by affecting glycolytic metabolite metabolism and decreasing the glycolytic flux. Moreover, PFK15 inhibited HemEC angiogenesis and migration and induced apoptosis via activation of the apoptosis pathway. Treatment with the combination of PFK15 with propranolol had a synergistic inhibitory effect on HemECs. Moreover, PFKFB3 knockdown markedly suppressed HemEC angiogenesis. Mechanistically, inhibition of PFKFB3 suppressed the PI3K-Akt signaling pathway and induced apoptotic cell death. More importantly, the suppression of PFKFB3 by PFK15 or shPFKFB3 led to markedly reduced tumor growth in vivo. CONCLUSIONS: Our findings suggest that PFKFB3 inhibition can suppress IH angiogenesis and induce apoptosis. Thus, targeting PFKFB3 may be a novel therapeutic strategy for IH.


Asunto(s)
Hemangioma , Fosfatidilinositol 3-Quinasas , Lactante , Ratones , Animales , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfofructoquinasa-2/metabolismo , Hemangioma/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Glucólisis , Glucosa/metabolismo , Proliferación Celular
4.
BMC Gastroenterol ; 23(1): 402, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37986145

RESUMEN

BACKGROUND: The objective of this study was to evaluate the safety and efficacy of laparoscopic Ladd's procedure (LL) for intestinal malrotation (IM) in small infants. METHODS: All patients aged < 6 months with IM who underwent Ladd's procedures between January 2012 and December 2019 were enrolled. The perioperative demographics and midterm follow-up results were retrospectively reviewed and compared between patients who underwent LL and open Ladd's operation (OL). RESULTS: Fifty-five patients were enrolled for analysis. The baseline characteristics were well matched in the two groups. The rate of volvulus was similar in the two groups (76.2% vs. 73.5%, P = 0.81). Two cases in the LL group were converted to OL due to intraoperative bleeding and intestinal swelling. The operative time (ORT) was not significantly different between the two groups (73.8 ± 18.7 vs. 66.8 ± 11.6 min, P = 0.76). Compared to the OL group, the LL group had a shorter time full feed (TFF) (3.1 ± 1.2 vs. 7.3 ± 1.9 days, P = 0.03) and a shorter postoperative hospital stay (PHS) than the OL group (5.5 ± 1.6 vs. 11.3 ± 2.7 days, P = 0.02). The rate of postoperative complications was similar in the two groups (9.5% vs. 11.8%, P = 0.47). The LL group had a lower rate of adhesive obstruction than the OL group, but the difference was not significant (0.0% vs. 11.8%, P = 0.09). One patient suffered recurrence in the LL group, while 0 patients suffered recurrence in the OL group (4.8% vs. 0.0%, P = 0.07). The rate of reoperation in the two groups was similar (4.8% vs. 8.8%). CONCLUSIONS: The LL procedure for IM in small infants was a safe and reliable method that had a satisfactory cosmetic appearance and shorter TFF and PHS than OL.


Asunto(s)
Vólvulo Intestinal , Laparoscopía , Lactante , Humanos , Vólvulo Intestinal/cirugía , Vólvulo Intestinal/complicaciones , Estudios de Seguimiento , Estudios Retrospectivos , Tiempo de Internación , Laparoscopía/efectos adversos , Laparoscopía/métodos
5.
BMC Surg ; 23(1): 204, 2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37464354

RESUMEN

BACKGROUND: The aim was to investigate the characteristics, surgical management, and outcomes of asymptomatic patients with antenatally diagnosed choledochal cysts (ADCCs) and to justify the strategy of laparoscopic surgery (LS) for them in our hospital. METHODS: We developed our LS strategy for asymptomatic ADCCs. Patients with asymptomatic ADCCs who underwent LS or open surgery (OS) during January 2010 and January 2020 were included. Patients with recorded symptomatic ADCCs were exclude. All data of group LS and group OS were statistically compared and analyzed. RESULTS: Twenty-five patients received LS and 18 patients received OS were included. There was no significant difference in baseline characteristics between the groups. A total of 65.1% of biliary sludge formation was detected preoperatively by ultrasonography (US) (72.0% in group LS, 55.6% in group OS, P = 0.26). Compared to the OS group, the LS group had a longer operative time (313.4 ± 27.2 vs. 154.0 ± 11.9 min, P = 0.02), shorter postoperative fasting period (3.1 ± 1.2 vs. 6.2 ± 2.3 days, P = 0.03), and shorter postoperative hospital stay (5.1 ± 1.9 vs. 9.2 ± 1.1 days, P = 0.03). The incidence of late complications, such as reflux cholangitis, adhesive intestinal obstruction, and biliary enteric anastomotic stricture with stone formation, was not significantly different between the two groups. The liver function and liver stiffness of all patients in the two groups were normal. CONCLUSIONS: Based on the strategy for asymptomatic ADCCs in our hospital, the perioperative safety and midterm follow-up results after LS were satisfactory and comparable to those after OS.


Asunto(s)
Quiste del Colédoco , Laparoscopía , Humanos , Quiste del Colédoco/diagnóstico por imagen , Quiste del Colédoco/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Laparoscopía/métodos , Hospitales , Complicaciones Posoperatorias/epidemiología , Tiempo de Internación
6.
J Vasc Surg ; 74(5): 1673-1681.e3, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34082006

RESUMEN

OBJECTIVE: Complicated vascular anomalies (VAs) can be intractable and uncontrollable using conventional treatment and can result in lethal outcomes. We undertook a prospective, multicenter phase II trial to evaluate the efficacy and safety of sirolimus in pediatric patients with complicated VAs. METHODS: Eligible patients were required to be aged 0 to 14 years and to have a complicated VA. The patients were treated with daily oral sirolimus for 12 months. The primary endpoint was the response, which was measured using sequential volumetric magnetic resonance imaging. The secondary endpoints were the disease severity score and quality of life. RESULTS: Of 126 patients enrolled on an intention-to-treat basis, 98 (77.8%) had had an objective response to sirolimus, with a ≥20% decrease in lesion volume. Compared with those with arteriovenous malformations, the response rates were higher (>80%) for patients with common lymphatic malformations, venous malformations, kaposiform hemangioendothelioma, and combined malformations with a prominent venous and/or lymphatic component (P < .05). Improvements in the disease severity score and quality of life were obtained in 83.3% and 79.4% of patients, respectively. The most common adverse event was mucositis in 47 patients. More serious adverse events included reversible grade 4 pneumonitis in 3 patients and grade 4 upper respiratory infection in 1 patient. All these adverse events were considered at least possibly related to the treatment. CONCLUSIONS: Sirolimus is an apparently effective option for pediatric patients with various types of complicated VAs. Close monitoring of possible adverse events is required. The results from the present trial are the basis for future prospective studies using new therapeutic approaches.


Asunto(s)
Sirolimus/uso terapéutico , Malformaciones Vasculares/tratamiento farmacológico , Adolescente , Niño , Preescolar , China , Femenino , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Sirolimus/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Malformaciones Vasculares/complicaciones , Malformaciones Vasculares/diagnóstico por imagen
7.
J Am Acad Dermatol ; 84(5): 1378-1384, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33285272

RESUMEN

BACKGROUND: Abdominal ultrasonography has been proposed to screen for infantile hepatic hemangioma (IHH) in patients with multiple cutaneous infantile hemangiomas (IHs). OBJECTIVES: The aim of this study was to establish the optimal cutoff point for the number of cutaneous IHs needed to screen for IHH. METHODS: We performed a prospective, multicenter study to screen for IHH in patients younger than 9 months who had multiple cutaneous IHs (n ≥ 3) on ultrasonography. For comparison, a group of patients with 1 or 2 focal cutaneous IHs was also recruited. RESULTS: In total, 676 patients with at least 3 cutaneous IHs and 980 patients with 1 or 2 focal cutaneous IHs were enrolled. Thirty-one patients were found to have IHH. A higher number of cutaneous IHs was associated with an increased risk of IHH (R = 0.973; P < .001). Receiver operating characteristic curve analysis showed that 5 cutaneous IHs was the optimal cutoff point to screen for IHH, with an area under the curve of 0.872 (P < .001; 95% confidence interval, 0.789-0.955). LIMITATIONS: This was an uncontrolled study. CONCLUSIONS: Screening for IHH is recommended in patients younger than 9 months who present with 5 or more cutaneous IHs.


Asunto(s)
Hemangioma/epidemiología , Neoplasias Hepáticas/epidemiología , Hígado/diagnóstico por imagen , Neoplasias Cutáneas/epidemiología , Comorbilidad , Femenino , Hemangioma/diagnóstico , Humanos , Incidencia , Lactante , Hígado/irrigación sanguínea , Neoplasias Hepáticas/diagnóstico , Masculino , Estudios Prospectivos , Factores de Riesgo , Piel/irrigación sanguínea , Ultrasonografía/estadística & datos numéricos
12.
Heliyon ; 10(7): e28802, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38576567

RESUMEN

The coexistence of kaposiform hemangioendothelioma (KHE) and capillary malformation (CM) is quite rare, and few relevant studies can be found to confirm whether this phenomenon is accidental. We diagnosed and treated two such patients, revealing interesting phenomena associated with the development of vascular diseases. These cases offer the possibility that the coexistence of KHE and CM is not accidental and open up a new field of research related to pediatric vascular tumors and vascular malformations. Personalization and precision are required in the diagnosis and treatment of such patients, and the present findings provide a reliable theoretical and practical basis for further research on the pathogenesis and therapy of patients with multiple vascular diseases.

13.
Biomed Pharmacother ; 178: 117181, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39059349

RESUMEN

Infantile hemangioma (IH) is the most common benign tumor in infants and usually resolves on its own. However, a small portion of IH cases are accompanied by serious complications and other problems, impacting the physical and psychological health of the children affected. The pathogenesis of IH is highly controversial. Studies have shown that abnormal blood vessel formation is an important pathological basis for the development of IH. Compared with that in normal tissues, the equilibrium of blood vessel growth at the tumor site is disrupted, and interactions among other types of cells, such as immune cells, promote the rapid proliferation and migration of vascular tissue cells and the construction of vascular networks. Currently, propranolol is the most common systemic drug used to inhibit the growth of IHs and accelerate their regression. The purpose of this review is to provide the latest research on the mechanisms of angiogenesis in IH. We discuss the possible roles of three major factors, namely, estrogen, hypoxia, and inflammation, in the development of IH. Additionally, we summarize the key roles of tumor cell subpopulations, such as pericytes, in the proliferation and regression of IH considering evidence from the past few years, with an emphasis on the possible mechanisms of propranolol in the treatment of IH. Angiogenesis is an important event during the development of IH, and an in-depth understanding of the molecular mechanisms of angiogenesis will provide new insights into the biology and clinical treatment of IH.

14.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(5): 496-502, 2024 May.
Artículo en Zh | MEDLINE | ID: mdl-38845496

RESUMEN

OBJECTIVE: To analyze the impact of cecal ligation and puncture (CLP)-induced sepsis on the proliferation and differentiation of intestinal epithelial cells. METHODS: (1) Animal experiment: sixteen male C57BL/6 mice were divided into sham operation group (Sham group) and CLP-induced sepsis model group (CLP group) by random number table method, with 8 mice in each group. After 5 days of operation, the jejunal tissues were taken for determination of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and intestinal alkaline phosphatase (IAP) by polymerase chain reaction (PCR). The translation of LGR5 was detected by Western blotting. The expression of proliferating cell nuclear antigen (Ki67) was analyzed by immunohistochemistry. IAP level was detected by modified calcium cobalt staining and colorimetry. Immunofluorescence staining was used to detect the expression of Paneth cell marker molecule lysozyme 1 (LYZ1) and goblet cell marker molecule mucin 2 (MUC2). (2) Cell experiment: IEC6 cells in logarithmic growth stage were divided into blank control group and lipopolysaccharide (LPS) group (LPS 5 µg/mL). Twenty-four hours after treatment, PCR and Western blotting were used to analyze the transcription and translation of LGR5. The proliferation of IEC6 cells were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining. The transcription and translation of IAP were detected by PCR and colorimetric method respectively. RESULTS: (1) Animal experiment: the immunohistochemical results showed that the positive rate of Ki67 staining in the jejunal tissue of CLP group was lower than that of Sham group [(41.7±2.5)% vs. (48.7±1.4)%, P = 0.01]. PCR and Western blotting results showed that there were no statistical differences in the mRNA and protein expressions of LGR5 in the jejunal tissue between the CLP group and Sham group (Lgr5 mRNA: 0.7±0.1 vs. 1.0±0.2, P = 0.11; LGR5/ß-actin: 0.83±0.17 vs. 0.68±0.19, P = 0.24). The mRNA (0.4±0.1 vs. 1.0±0.1, P < 0.01) and protein (U/g: 47.3±6.0 vs. 73.1±15.3, P < 0.01) levels of IAP in the jejunal tissue were lower in CLP group. Immunofluorescence saining analysis showed that the expressions of LYZ1 and MUC2 in the CLP group were lower than those in the Sham group. (2) Cell experiment: PCR and Western blotting results showed that there was no significant difference in the expression of LGR5 between the LPS group and the blank control group (Lgr5 mRNA: 0.9±0.1 vs. 1.0±0.2, P = 0.33; LGR5/ß-actin: 0.71±0.18 vs. 0.69±0.04, P = 0.81). The proliferation rate of IEC6 cells in the LPS group was lower than that in the blank control group, but there was no significant difference [positivity rate of EdU: (40.5±3.8)% vs. (46.5±3.6)%, P = 0.11]. The mRNA (0.5±0.1 vs. 1.0±0.2, P < 0.01) and protein (U/g: 15.0±4.0 vs. 41.2±10.4, P < 0.01) of IAP in the LPS group were lower than those in the blank control group. CONCLUSIONS: CLP-induced sepsis inhibits the proliferation and differentiation of intestinal epithelial cells, impairing the self-renewal ability of intestinal epithelium.


Asunto(s)
Diferenciación Celular , Proliferación Celular , Ratones Endogámicos C57BL , Receptores Acoplados a Proteínas G , Sepsis , Células Madre , Animales , Masculino , Sepsis/metabolismo , Ratones , Receptores Acoplados a Proteínas G/metabolismo , Células Madre/metabolismo , Células Madre/citología , Ciego , Mucosa Intestinal/metabolismo , Ligadura , Mucina 2
15.
J Pediatr Surg ; 59(4): 599-604, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38158257

RESUMEN

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor that often occurs in infants and young children. The goal of this study was to analyze the clinical characteristics of KHE patients with bone destruction and provide clinical guidance for diagnosis and treatment. METHODS: We conducted a descriptive cohort study with follow-up from January 2007 to January 2023 to collect demographic information and tumor-related clinical information from KHE patients with bone destruction. RESULTS: A total of 269 KHE patients were included in the study, of whom 70 (26.0%) patients had tumors with bone destruction. The median age at diagnosis of patients with bone destruction was 19.0 months, which was much later than that of patients without bone destruction (P < 0.001). Patients with bone destruction were more likely to have a decreased range of motion (ROM) (P < 0.001). Metaphysis involvement was more likely to occur in the lower limb bones (P = 0.039), and the lower limb bones were more likely to be associated with decreased ROM (P = 0.001). Tumors involving extracompartmental bone were more likely to have decreased ROM (P = 0.003) and exhibit the Kasabach-Merritt phenomenon (P = 0.006). CONCLUSIONS: Based on the rarity and significant heterogeneity of KHE patients with bone destruction, we should give full play to the role of multidisciplinary teams in addressing disease to reduce the long-term complications of KHE with bone destruction and improve the quality of life of patients. TYPE OF STUDY: Prognostic Study. LEVEL OF EVIDENCE: Level II.


Asunto(s)
Hemangioendotelioma , Síndrome de Kasabach-Merritt , Sarcoma de Kaposi , Lactante , Niño , Humanos , Preescolar , Síndrome de Kasabach-Merritt/terapia , Síndrome de Kasabach-Merritt/tratamiento farmacológico , Estudios de Seguimiento , Estudios de Cohortes , Calidad de Vida , Estudios Retrospectivos , Hemangioendotelioma/diagnóstico , Hemangioendotelioma/terapia , Hemangioendotelioma/complicaciones , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/terapia , Sarcoma de Kaposi/complicaciones , Pronóstico
16.
J Pediatr Surg ; 59(4): 621-626, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38182536

RESUMEN

INTRODUCTION: There are limited studies revealing the association between serum albumin concentrations and acute kidney injury (AKI) in critically ill children. METHODS: This was a multicenter retrospective study. Children consecutively admitted to four pediatric surgical intensive care units (PSICUs) between January 2016 and December 2020 were screened for analysis. Patients without recorded albumin values during the PSICU stay were excluded. Data were extracted from the electronic medical records systems of the hospitals. AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. The associations between serum albumin levels and AKI were assessed by using logistic regression models. RESULTS: A total of 7802 children were included in the analysis. The median age of the children was 1.0 (interquartile range (IQR), 0.0-4.0) years. There were 3214 (41.2 %) children who developed AKI. In the univariate logistic regression model, serum albumin levels were associated with AKI (odds ratio (OR) = 1.04, 95 % confidence interval (CI) 1.04-1.05). After adjusting for covariates, serum albumin showed an independent association with AKI (OR = 1.04, 95 % CI 1.03-1.05). Albumin levels above 39.43 g/L (OR = 1.036, 95 % CI 1.002-1.070) were associated with AKI in the unadjusted cubic spline. In the adjusted cubic spline, albumin levels above 40.41 g/L (OR = 1.061, 95 % CI 1.003-1.122) were associated with AKI. CONCLUSION: High serum albumin was associated with AKI in critically ill children in the PSICU. Further studies are needed to validate our findings. TYPE OF STUDY: Prognostic Study. LEVEL OF EVIDENCE: LEVEL II.


Asunto(s)
Lesión Renal Aguda , Enfermedad Crítica , Niño , Humanos , Estudios Retrospectivos , Factores de Riesgo , Unidades de Cuidado Intensivo Pediátrico , Albúmina Sérica , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Cuidados Críticos , Unidades de Cuidados Intensivos
17.
Front Pediatr ; 11: 1203336, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37664553

RESUMEN

Introduction: Kaposiform lymphangiomatosis (KLA) is a rare and complex lymphatic anomaly with a poor prognosis. There is no standard treatment, and drug therapies are the most common therapeutic method. However, some patients' symptoms become gradually aggravated despite medical treatment. Splenectomy may be an alternative option when pharmacological therapies are ineffective. Materials and Methods: We reviewed and evaluated the cases of 3 patients with KLA who ultimately underwent splenectomy. Results: The lesions were diffusely distributed and involved the lungs and spleens of the 3 patients. Laboratory examinations revealed that all three patients had thrombocytopenia and reduced fibrinogen levels. All patients underwent symptomatic splenectomy after the medication failed. Surprisingly, their symptoms greatly improved. Histopathological investigation of the splenic lesions of the three patients confirmed the diagnosis of KLA. Immunohistochemical staining showed positivity for CD31, CD34, podoplanin, Prox-1 and angiopoietin 2 (Ang-2). Discussion: This study aimed to review the features of KLA patients treated by splenectomy and explore the underlying link between splenectomy and prognosis. The reason for the improvement after splenectomy may be related to increased Ang-2 levels and platelet activation in patients with KLA. Future research should seek to develop more targeted drugs based on molecular findings, which may give new hope for the treatment of KLA.

18.
Front Oncol ; 13: 1097997, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37205203

RESUMEN

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that causes progressive angiogenesis and lymphangiogenesis, which often occurs in the skin or soft tissue, with an acute onset and rapid progression. A 4-year-old girl was admitted to our hospital with a 2-year history of thrombocytopenia, combined with right hepatic atrophy and pancreatic lesion for 3 months. At the age of two, she developed purpura and thrombocytopenia was detected, after treatment with gamma globulin and corticosteroids, the platelet count normalized, but it dropped immediately at lower doses. One year after the cessation of corticosteroids therapy, the patient presented with abdominal pain and abnormal liver function and the magnetic resonance imaging (MRI) revealed right hepatic atrophy and pancreatic occupancy, but the first liver biopsy did not reveal any positive pathological results. By analyzing the clinical manifestations in conjunction with MRI and abnormal coagulation, we considered that the patient might be diagnosed as KHE with Kasabach-Merritt phenomenon, however, sirolimus treatment was ineffective and pancreatic biopsy only showed a tendency for tumors of vascular origin. Finally, we performed a Whipple operation after the right hepatic artery embolization, histological and immunohistochemical examination suggested KHE. Three months postoperatively, the patient's liver function, pancreatic enzymes and blood clotting function gradually returned to normal. KHEs may result in significant blood loss with worsening of the coagulopathy and functional impairment, timely surgical intervention for KHE is necessary when non-invasive or minimally invasive treatment is ineffective, or the symptoms of tumor compression are obvious.

19.
Front Physiol ; 14: 1199063, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37700759

RESUMEN

Introduction: The aim of this study was to investigate the status of serum procalcitonin (PCT) in patients stung by wasps and evaluate the association between PCT levels and acute kidney injury (AKI). Methods: Patients stung by wasps admitted to two tertiary hospitals between January 2017 and December 2020 were screened for enrollment. We evaluated serum PCT levels on admission in patients stung by wasps. The patients were divided into an AKI group and a non-AKI group. A logistic regression model was used to analyze the association between PCT status and AKI. The performance of PCT concentrations in predicting the occurrence of AKI was evaluated by the area under the receiver operating characteristic curve (AUROC). Results: A total of 138 patients were enrolled, and 66 patients suffered AKI. PCT levels were elevated in 78.99% of patients stung by wasps. Nearly half of the patients (47.83%) developed AKI. PCT levels were correlated with creatinine levels on admission (r = 0.787, 95% CI: 0.713-0.844). PCT levels in patients with AKI were higher than those in patients without AKI (p < 0.001). After adjustment for covariates, PCT levels on admission were independently associated with AKI (OR: 1.575, 95% CI: 1.071-2.317, p = 0.021). The AUROC of PCT levels on admission was 0.837 (95% CI, 0.771-0.902, p < 0.001). A PCT level of 0.57 µg/L was the cutoff for maximizing the Youden index; the specificity was 79.45%, and the sensitivity was 73.43%. Conclusion: Serum PCT levels may be a potential biomarker of AKI in patients stung by wasps.

20.
Biochem Pharmacol ; 218: 115922, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37956892

RESUMEN

Infantile hemangioma (IH) is the most common benign tumor in children. Propranolol is the first-line treatment for IH, but the underlying mechanism of propranolol treatment in IH is not completely understood. Integrated transcriptional and metabolic analyses were performed to investigate the metabolic changes in hemangioma-derived endothelial cells (HemECs) after propranolol treatment. The findings were then further validated through independent cell experiments using a Seahorse XFp analyzer, Western blotting, immunohistochemistry and mitochondrial functional assays. Thirty-four differentially expressed metabolites, including the glycolysis metabolites glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-bisphosphate, were identified by targeted metabolomics. A KEGG pathway enrichment analysis showed that the disturbances in these metabolites were highly related to glucose metabolism-related pathways, including the pentose phosphate pathway, the Warburg effect, glycolysis and the citric acid cycle. Transcriptional analysis revealed that metabolism-related pathways, including glycine, serine and threonine metabolism, tyrosine metabolism, and glutathione metabolism, were highly enriched. Moreover, integration of the metabolomic and transcriptomic data revealed that glucose metabolism-related pathways, particularly glycolysis, were altered after propranolol treatment. Cell experiments demonstrated that HemECs exhibited higher levels of glycolysis than human umbilical vein ECs (HUVECs) and that propranolol suppressed glycolysis in HemECs. In conclusion, propranolol inhibited glucose metabolism in HemECs by suppressing glucose metabolic pathways, particularly glycolysis.


Asunto(s)
Células Endoteliales , Hemangioma , Niño , Humanos , Células Endoteliales/metabolismo , Propranolol/farmacología , Propranolol/metabolismo , Transducción de Señal , Proliferación Celular , Hemangioma/tratamiento farmacológico , Hemangioma/metabolismo , Hemangioma/patología , Glucosa/metabolismo , Fosfatos/farmacología
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