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BACKGROUND: This study aimed to compare the regressive effects of aflibercept and faricimab on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration. METHODS: In total, 41 eyes of 40 patients diagnosed with type 1 macular neovascularization were retrospectively analyzed using multimodal imaging. Of these, 23 eyes were treated with intravitreal aflibercept injections (IVA group), and 18 eyes were treated with intravitreal faricimab (IVFa group), with 3 consecutive injections administered as loading dose therapy. Before treatment and at 1, 2, and 3 months after the first treatment, the maximum height (MH) and maximum diameter (MD) of the PED were measured using optical coherence tomography in each treatment group. RESULTS: In the IVA group, the MH at baseline (215 ± 177 µm) was reduced to 141 ± 150 (P = 0.06), 119 ± 150 (P < 0.01), and 107 ± 150 µm (P < 0.0001) at 1, 2, and 3 months after treatment, respectively. Similarly, in the IVFa group, the MH decreased from 240 ± 195 µm before treatment to 165 ± 170 µm (P = 0.24), 139 ± 142 µm (P < 0.05), and 117 ± 112 µm (P < 0.01) at 1, 2, and 3 months after treatment, respectively. The reduction at 2 and 3 months was significant in both treatments. The mean changes of MH from baseline were -108 ± 142 µm in the IVA group and -124 ± 112 µm in the IVFa group, with no significant difference (P = 0.21). In both groups, the MD did not regress significantly. CONCLUSIONS: The results suggested that the MH of the PED between the IVA and IVFa groups regressed similarly after each loading therapy.
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Inhibidores de la Angiogénesis , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Desprendimiento de Retina , Epitelio Pigmentado de la Retina , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Masculino , Femenino , Estudios Retrospectivos , Desprendimiento de Retina/tratamiento farmacológico , Desprendimiento de Retina/diagnóstico , Anciano , Tomografía de Coherencia Óptica/métodos , Inhibidores de la Angiogénesis/uso terapéutico , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/fisiopatología , Anciano de 80 o más Años , Persona de Mediana Edad , Angiografía con Fluoresceína , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Tissue mechanical properties are determined mainly by the extracellular matrix (ECM) and actively maintained by resident cells. Despite its broad importance to biology and medicine, tissue mechanical homeostasis remains poorly understood. To explore cell-mediated control of tissue stiffness, we developed mutations in the mechanosensitive protein talin 1 to alter cellular sensing of ECM. Mutation of a mechanosensitive site between talin 1 rod-domain helix bundles R1 and R2 increased cell spreading and tension exertion on compliant substrates. These mutations promote binding of the ARP2/3 complex subunit ARPC5L, which mediates the change in substrate stiffness sensing. Ascending aortas from mice bearing these mutations showed less fibrillar collagen, reduced axial stiffness, and lower rupture pressure. Together, these results demonstrate that cellular stiffness sensing contributes to ECM mechanics, directly supporting the mechanical homeostasis hypothesis and identifying a mechanosensitive interaction within talin that contributes to this mechanism.
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Matriz Extracelular , Homeostasis , Talina , Talina/metabolismo , Talina/genética , Animales , Ratones , Matriz Extracelular/metabolismo , Humanos , Mecanotransducción Celular , Mutación , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Complejo 2-3 Proteico Relacionado con la Actina/genética , Aorta/metabolismo , Unión Proteica , Fenómenos BiomecánicosRESUMEN
Thanatophoric dysplasia (TD) is a rare and severe type of skeletal dysplasia. Typical clinical findings include macrocephaly, shortening of the four limbs, underdeveloped lungs, and thoracic hypoplasia. Neonates with TD develop severe respiratory problems due to thoracic hypoplasia and require respiratory management for survival. Despite the resolution of respiratory problems, long-term survival cases are rare. Previous studies have reported that surgical procedures in patients with TD are limited to those necessary for survival, including tracheostomy, laminectomy, and ventricular shunt. A 1-year-old boy with TD was treated with laparoscopic herniorrhaphy. To the best of our knowledge, this is the first report of TD treated with laparoscopic procedure.
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Hernia Inguinal , Herniorrafia , Laparoscopía , Displasia Tanatofórica , Humanos , Masculino , Hernia Inguinal/cirugía , Hernia Inguinal/complicaciones , Herniorrafia/métodos , Displasia Tanatofórica/cirugía , Displasia Tanatofórica/complicaciones , LactanteRESUMEN
Endothelial cell responses to fluid shear stress from blood flow are crucial for vascular development, function and disease. A complex of PECAM-1, VE-cadherin, VEGF receptors (VEGFRs) and PlexinD1 located at cell-cell junctions mediates many of these events. But available evidence suggests that another mechanosensor upstream of PECAM-1 initiates signaling. Hypothesizing that GPCR and Gα proteins may serve this role, we performed siRNA screening of Gα subunits and found that Gαi2 and Gαq/11 are required for activation of the junctional complex. We then developed a new activation assay, which showed that these G proteins are activated by flow. We next mapped the Gα residues required for activation and developed an affinity purification method that used this information to identify latrophilin-2 (Lphn-2/ADGRL2) as the upstream GPCR. Latrophilin-2 is required for all PECAM-1 downstream events tested. In both mice and zebrafish, latrophilin-2 is required for flow-dependent angiogenesis and artery remodeling. Furthermore, endothelial specific knockout demonstrates that latrophilin plays a role in flow-dependent artery remodeling. Human genetic data reveal a correlation between the latrophilin-2-encoding Adgrl2 gene and cardiovascular disease. Together, these results define a pathway that connects latrophilin-dependent G protein activation to subsequent endothelial signaling, vascular physiology and disease.
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Endothelial cell responses to fluid shear stress from blood flow are crucial for vascular development, function, and disease. A complex of PECAM-1, VE-cadherin, VEGF receptors (VEGFRs), and Plexin D1 located at cell-cell junctions mediates many of these events. However, available evidence suggests that another mechanosensor upstream of PECAM-1 initiates signaling. Hypothesizing that GPCR and Gα proteins may serve this role, we performed siRNA screening of Gα subunits and found that Gαi2 and Gαq/11 are required for activation of the junctional complex. We then developed a new activation assay, which showed that these G proteins are activated by flow. We next mapped the Gα residues required for activation and developed an affinity purification method that used this information to identify latrophilin-2 (Lphn2/ADGRL2) as the upstream GPCR. Latrophilin-2 is required for all PECAM-1 downstream events tested. In both mice and zebrafish, latrophilin-2 is required for flow-dependent angiogenesis and artery remodeling. Furthermore, endothelial-specific knockout demonstrates that latrophilin plays a role in flow-dependent artery remodeling. Human genetic data reveal a correlation between the latrophilin-2-encoding Adgrl2 gene and cardiovascular disease. Together, these results define a pathway that connects latrophilin-dependent G protein activation to subsequent endothelial signaling, vascular physiology, and disease.
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Uniones Intercelulares , Mecanotransducción Celular , Receptores Acoplados a Proteínas G , Receptores de Péptidos , Animales , Humanos , Ratones , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Uniones Intercelulares/metabolismo , Uniones Intercelulares/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de Péptidos/metabolismo , Receptores de Péptidos/genética , Estrés Mecánico , Pez Cebra/metabolismo , Pez Cebra/genéticaRESUMEN
PURPOSE: To investigate the association between the arm-to-choroidal circulation time (ACT) on indocyanine green angiography (IA) and clinical profile in patients with polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: Single-center retrospective study. METHODS: We included 38 eyes of 38 patients with PCV diagnosed using multimodal imaging and did not undergo previous treatment. All patients were treated with monthly aflibercept injections for 3 months and treat-and-extend regimens for the subsequent 12 months. Posterior vortex vein ACT was assessed on the first visit using Heidelberg IA. The patients were divided into two groups: ACT ≥20 s (L group; eight eyes) and ACT <20 s (S group; 30 eyes). The clinical profiles before and after treatment were analyzed to assess associations with ACT. RESULTS: The mean ACT was 16.39±3.3 s (L group: 21.25±1.49 s, women:men=2:6, mean age: 77.3±6.5 years; S group: 15.10±2.17 s, women:men=7:23, mean age: 75.5±6.9 years). No significant difference was observed in the mean subfoveal choroidal thickness between the L and the S groups (176±75 µm vs. 230±79 µm, P=0.10). However, there were significant differences between the L and S groups in retinal fluid accumulation and hemorrhage recurrence (eight/eight eyes, 100% vs. 13/30 eyes, 43%, P<0.001), mean aflibercept injections (8.8±1.6 vs. 7.0±1.6, P<0.01) during the 12-month period, and the number of polypoidal lesions (1.8±0.7 vs. 1.3±0.5, P<0.05). CONCLUSION: Patients with PCV and ACT >20 s are more likely to experience exudative change recurrence in the retina during treatment because they have more polypoidal lesions.
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Coroides , Fondo de Ojo , Vasculopatía Coroidea Polipoidea , Pólipos , Receptores de Factores de Crecimiento Endotelial Vascular , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Velocidad del Flujo Sanguíneo/fisiología , Coroides/irrigación sanguínea , Coroides/diagnóstico por imagen , Colorantes/administración & dosificación , Angiografía con Fluoresceína/métodos , Estudios de Seguimiento , Verde de Indocianina/administración & dosificación , Inyecciones Intravítreas , Imagen Multimodal , Vasculopatía Coroidea Polipoidea/diagnóstico , Vasculopatía Coroidea Polipoidea/tratamiento farmacológico , Pólipos/diagnóstico , Pólipos/tratamiento farmacológico , Pólipos/fisiopatología , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Flujo Sanguíneo Regional/fisiología , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Agudeza VisualRESUMEN
PURPOSE: To assess the changes in intraocular pressure (IOP) after intravitreal aflibercept injections in Japanese patients with neovascular age-related macular degeneration (nAMD) complicated by glaucoma. STUDY DESIGN: Retrospective observational study. METHODS: We retrospectively reviewed 27 eyes of 25 Japanese patients diagnosed with nAMD complicated by glaucoma. The patients were treated with 2 mg/0.05 ml of aflibercept and followed for 52 weeks according to a treat-and-extend (TAE) regimen after 3 consecutive monthly injections. The IOP of each eye was measured at each visit using non-contact tonometry. IOP changes as well as additional glaucoma treatments during 52 weeks were recorded. RESULTS: The mean of aflibercept injections was 8.3 ± 1.9. The mean IOP at baseline was 14.0 ± 3.1 mmHg, and the mean IOP after aflibercept therapy was 13.0 ± 2.4 mmHg at the final visit (P = 0.0463). No patients received additional glaucoma treatment of eye drops or surgery. CONCLUSION: Our results suggest that intravitreal aflibercept injections may be beneficial for patients with nAMD complicated by glaucoma.
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Glaucoma , Degeneración Macular , Humanos , Inhibidores de la Angiogénesis , Glaucoma/tratamiento farmacológico , Presión Intraocular , Inyecciones Intravítreas , Japón/epidemiología , Degeneración Macular/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: Hernioplasty is one of the most commonly performed surgeries. However, the optimal procedure for young adults has not been defined yet. Our study compared the outcomes of laparoscopic percutaneous extraperitoneal closure (LPEC) in young adults with outcomes in children. MATERIAL AND METHODS: We retrospectively reviewed patients aged 0-30 years who underwent LPEC. Data regarding age, sex, hernia type, surgical time, pre-intraoperative laterality, contralateral patent processus vaginalis (CPPV), and complications were analyzed. RESULTS: LPEC was performed on 2642 patients in our hospital. Of these, 51 patients were young adults (aged 15-30 years). Asymptomatic CPPV in unilateral patients was frequent in the <15-year age group (50.2%) compared to the 15-30-year age group (15.9%). The median surgical time was shorter in the <15-year age group (19 min, interquartile range [IQR]: 24-33) compared to that of the 15-30-year age group (33 min, IQR: 23.3-40.8). CONCLUSIONS: This is the first report on the outcomes in young adult patients who underwent LPEC. The median surgical time was longer in the 15-30-year age group than in the <15-year age group. The median follow-up was 4.7 years with no intra-postoperative complications, such as postoperative bleeding, infection, persistent pain, and recurrence. LPEC is an effective, cosmetic, and safe surgical treatment in young adults and children.
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Hernia Inguinal , Laparoscopía , Niño , Humanos , Adulto Joven , Lactante , Adolescente , Adulto , Hernia Inguinal/cirugía , Resultado del Tratamiento , Estudios Retrospectivos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Herniorrafia/métodosRESUMEN
It is widely believed that tissue mechanical properties, determined mainly by the extracellular matrix (ECM), are actively maintained. However, despite its broad importance to biology and medicine, tissue mechanical homeostasis is poorly understood. To explore this hypothesis, we developed mutations in the mechanosensitive protein talin1 that alter cellular sensing of ECM stiffness. Mutation of a novel mechanosensitive site between talin1 rod domain helix bundles 1 and 2 (R1 and R2) shifted cellular stiffness sensing curves, enabling cells to spread and exert tension on compliant substrates. Opening of the R1-R2 interface promotes binding of the ARP2/3 complex subunit ARPC5L, which mediates the altered stiffness sensing. Ascending aortas from mice bearing these mutations show increased compliance, less fibrillar collagen, and rupture at lower pressure. Together, these results demonstrate that cellular stiffness sensing regulates ECM mechanical properties. These data thus directly support the mechanical homeostasis hypothesis and identify a novel mechanosensitive interaction within talin that contributes to this mechanism.
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Sixty-seven patients (38 woman; median age, 69 years) were enrolled to assess complement activation products (CAPs) in tear fluid with/without dry eye (DE) and with/without meibomian gland dysfunction (MGD). Patients were divided into four groups based on the presence/absence of DE and MGD: group DM had both DE and MGD, group DN had DE without MGD, group NM had MGD without DE, and group NN had neither DE nor MGD. The levels of C3a and C5a in the collected tears were analyzed using a cytometric bead array. The C3a concentrations in the DM, DN, NM, and NN groups were 2326 pg/ml, 1411 pg/ml, 1821 pg/ml, and 978 pg/ml, respectively. The C5a concentrations in the DM, DN, NM, and NN groups were 24.7 pg/ml, 15.3 pg/ml, 24.1 pg/ml, and 12.9 pg/ml, respectively. The concentrations of C3a and C5a in the DM and NM groups were significantly higher than in the NN group (P < 0.05 for both comparisons). The CAPs in the tear fluid in MGD and DE increased. Local dysregulation of the innate immune system can be associated with the development of MGD and DE in elderly patients.
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Síndromes de Ojo Seco , Disfunción de la Glándula de Meibomio , Femenino , Humanos , Anciano , Glándulas Tarsales , Lágrimas , Activación de ComplementoRESUMEN
PURPOSE: Due to technological advancements, surgical invasiveness has been reduced. However, cataract surgery has been implicated in causing postoperative inflammation, including dry eye syndrome. The innate immune system may be involved in postoperative inflammation, and complement activation could potentially play a crucial role in defense against pathogens, homeostasis, and wound healing. To investigate changes in the tear film complement activation products (CAPs) and ocular surface after vitrectomy combined with cataract surgery. METHODS: Forty-three patients (23 women; median age, 69 years) were enrolled in this prospective study and underwent phacoemulsification and vitrectomy. We measured Schirmer's test (ST) and CAPs in the tears at baseline (the day before surgery), 4 days and 1 month after the surgery. Tears were collected in microtubes. The CAPs in the tear fluid were analyzed by cytometric bead array. RESULTS: The median ST (8.5 mm) at baseline increased to 16 mm at 4 days ( P < 0.001) and 10 mm at 1 month (P = 0.44). The C3a levels (1202 pg/ml) at baseline increased to 2753 pg/ml at 4 days (P < 0.001), and 1763 pg/ml at 1 month (P = 0.049). The C4a levels (476 pg/ml) at baseline increased to 880 pg/ml at 4 days (P < 0.001), and 657 pg/ml at 1 month (P = 0.013). The C5a levels (22.6 pg/ml) at baseline increased to 470.9 pg/ml at 4 days (P < 0.001), and 38.3 pg/ml at 1 month (P = 0.0048). The surgical eyes were divided into the short ST group (⦠10 mm, n = 22) and long ST group (> 10 mm, n = 21) based on the preoperative ST values. At 1 month postoperatively, the C3a levels were 2194 pg/ml in the preoperative short ST group and 1391 pg/ml in the long ST group, with significantly higher C3a concentrations in the short ST group (P < 0.001). CONCLUSIONS: The CAPs levels in tears increased after vitrectomy combined with cataract surgery. A preoperative deficit in tear secretion might induce prolonged complement activation and delayed recovery of ocular surface parameters postoperatively.
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Catarata , Síndromes de Ojo Seco , Oftalmología , Humanos , Femenino , Anciano , Estudios Prospectivos , Síndromes de Ojo Seco/etiología , Lágrimas/fisiología , Catarata/complicaciones , Activación de ComplementoRESUMEN
BACKGROUND: Marfan syndrome, caused by mutations in the gene for fibrillin-1, leads to thoracic aortic aneurysms (TAAs). Phenotypic modulation of vascular smooth muscle cells (SMCs) and ECM (extracellular matrix) remodeling are characteristic of both nonsyndromic and Marfan aneurysms. The ECM protein FN (fibronectin) is elevated in the tunica media of TAAs and amplifies inflammatory signaling in endothelial and SMCs through its main receptor, integrin α5ß1. We investigated the role of integrin α5-specific signals in Marfan mice in which the cytoplasmic domain of integrin α5 was replaced with that of integrin α2 (denoted α5/2 chimera). METHODS: We crossed α5/2 chimeric mice with Fbn1mgR/mgR mice (mgR model of Marfan syndrome) to evaluate the survival rate and pathogenesis of TAAs among wild-type, α5/2, mgR, and α5/2 mgR mice. Further biochemical and microscopic analysis of porcine and mouse aortic SMCs investigated molecular mechanisms by which FN affects SMCs and subsequent development of TAAs. RESULTS: FN was elevated in the thoracic aortas from Marfan patients, in nonsyndromic aneurysms, and in mgR mice. The α5/2 mutation greatly prolonged survival of Marfan mice, with improved elastic fiber integrity, mechanical properties, SMC density, and SMC contractile gene expression. Furthermore, plating of wild-type SMCs on FN decreased contractile gene expression and activated inflammatory pathways whereas α5/2 SMCs were resistant. These effects correlated with increased NF-kB activation in cultured SMCs and mgR aortas, which was alleviated by the α5/2 mutation or NF-kB inhibition. CONCLUSIONS: FN-integrin α5 signaling is a significant driver of TAA in the mgR mouse model. This pathway thus warrants further investigation as a therapeutic target.
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Aneurisma de la Aorta Torácica , Síndrome de Marfan , Ratones , Animales , Porcinos , Síndrome de Marfan/complicaciones , Síndrome de Marfan/genética , Síndrome de Marfan/metabolismo , Integrina alfa5/uso terapéutico , Fibronectinas , FN-kappa B , Aneurisma de la Aorta Torácica/genética , Aneurisma de la Aorta Torácica/prevención & control , Fibrilina-1/genéticaRESUMEN
BACKGROUND: Inguinal hernia repair is one of the most common operations performed worldwide. No consensus currently exists regarding the most appropriate operation for inguinal hernia in adolescent and young adult (AYA) patients. This study aimed to evaluate the outcomes in AYA patients undergoing high ligation or mesh repair under laparoscopy by examining the location and size of the hernia orifice defect. METHODS: We retrospectively reviewed all patients aged 15 to 40 years old who underwent laparoscopic hernia repair. Under single port laparoscopy, we classified the anatomic location (lateral, medial, or femoral) and size of the hernia orifice according to the classification by the European Hernia Society (EHS). A laparoscopic percutaneous extraperitoneal closure (LPEC) was performed on the patients with a lateral hernia with a hernia orifice defect size of ≤1.5 cm (L1). Transabdominal preperitoneal (TAPP) repair was performed on the patients with a lateral hernia with a hernia orifice defect size of >1.5 cm (L2 or 3). RESULTS: Overall, 40 patients underwent the mentioned surgical procedures. We performed LPEC on 22 patients, and TAPP on 18 patients. There were no intraoperative or postoperative complications and recurrences. CONCLUSIONS: This is the first report that evaluated the outcomes of AYA patients who underwent high ligation or mesh repair under laparoscopy by examining the location and size of the hernia orifice defect. Our data indicated that LPEC were effective and safe for AYA patients with small hernia orifice defect.
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Hernia Inguinal , Laparoscopía , Humanos , Adolescente , Adulto Joven , Adulto , Hernia Inguinal/cirugía , Estudios Retrospectivos , Mallas Quirúrgicas , Laparoscopía/métodos , Complicaciones PosoperatoriasRESUMEN
PURPOSE: Screening for undescended testis (UDT) in Japan is performed as a neonate, then at 1, 3, 10, and 18 months old, and 3 years old. Incidence of ascending testis (AT) after screening was reviewed. METHODS: All orchiopexy/orchiectomy at a single institute between July 2005 and June 2022 were reviewed retrospectively. RESULTS: 376 boys had 422 procedures; 54/422 (12.8%) were in 48 boys ≥ 4 years old (mean age: 6.7 years; range: 4-13); testes were normal (n = 22; 40.7%), small (n = 25; 46.2%), or atrophied (n = 7; 1.3%). There were 47 orchiopexies and 7 orchiectomies for atrophy. Incidence of AT in boys ≥ 4 years old was 24/422 (5.7%). Of these, 16/422 (3.8%) developed after normal descent and 8/422 (1.9%) were associated with retractile testis (AT + RET). Other indications included delayed treatment for UDT (n = 13), late referral by pediatricians (n = 10), and iatrogenic UDT (n = 6). Surgical intervention in boys ≥ 4 years old (12.8%) was less than that reported in the West (range: 30-50%) as was AT: (5.7% versus 15.4%) and AT + RET (1.9% versus 13.8%). CONCLUSIONS: Comprehensive UDT screening probably contributed to the lower incidence of surgery and AT (especially AT + RET) in boys ≥ 4 years old.
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Criptorquidismo , Masculino , Recién Nacido , Humanos , Lactante , Niño , Preescolar , Criptorquidismo/diagnóstico , Criptorquidismo/epidemiología , Criptorquidismo/cirugía , Testículo , Incidencia , Estudios Retrospectivos , Japón/epidemiología , Orquidopexia/métodosRESUMEN
Vascular complications are a major cause of illness and death in patients with type 1 diabetes (T1D). Diabetic vascular basement membranes are enriched in fibronectin (FN), an extracellular matrix protein that amplifies inflammatory signaling in endothelial cells through its main receptor, integrin α5ß1. Binding of the integrin α5 cytoplasmic domain to phosphodiesterase 4D5 (PDE4D5), which increases phosphodiesterase catalytic activity and inhibits antiinflammatory cAMP signaling, was found to mediate these effects. Here, we examined mice in which the integrin α5 cytoplasmic domain is replaced by that of α2 (integrin α5/2) or the integrin α5 binding site in PDE4D is mutated (PDE4Dmut). T1D was induced via injection of streptozotocin and hyperlipidemia induced via injection of PCSK9 virus and provision of a high-fat diet. We found that in T1D and hyperlipidemia, the integrin α5/2 mutation reduced atherosclerosis plaque size by â¼50%, with reduced inflammatory cell invasion and metalloproteinase expression. Integrin α5/2 T1D mice also had improved blood-flow recovery from hindlimb ischemia and improved biomechanical properties of the carotid artery. By contrast, the PDE4Dmut had no beneficial effects in T1D. FN signaling through integrin α5 is thus a major contributor to diabetic vascular disease but not through its interaction with PDE4D.
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Diabetes Mellitus Tipo 1 , Fibronectinas , Integrina alfa5 , Animales , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo , Células Endoteliales/metabolismo , Fibronectinas/metabolismo , Integrina alfa5/metabolismo , Ratones , Transducción de SeñalRESUMEN
OBJECTIVE: To examine pathophysiology of parameatal urethral cyst (PUC) with comparison between the surgical excision group and the spontaneous resolution group. METHODS: We retrospectively reviewed all patients diagnosed with PUC and aged ≤15 years. Initially, all the patients received observation without any treatment. The indication of surgical excision was family preference. The patients were analyzed according to their sex, age, symptoms, clinical course, and pathological examination findings. RESULTS: Among the 54 boys visited our hospital for PUC. The median age at presentation was 35 (IQR: 12-50) months, including 7 (13.0%) neonates cases. In total, 38 (70.4%) patients were underwent surgical excision, 12 (22.2%) had spontaneous resolution during observation, 1 (1.9%) had observation without resolution, and 3 (5.6%) were lost to follow-up. The median size of PUC at the first visit was significantly larger in the surgical excision group (5 mm median, IQR 3-5) than in the spontaneous resolution group (1.5 mm median, IQR 1-2.5) (P <.0001). In this study, PUC ≥5 mm in diameter did not have spontaneous resolution. CONCLUSION: This is the largest study of PUC conducted at a single institute. This study indicated that 22% of PUCs had spontaneous resolution, and PUCs <5 mm had potential for spontaneous resolution. The results recommend an observation of at least 5.5 months for patients with asymptomatic PUC <5 mm. By contrast, we recommend the surgical excision for symptomatic PUC ≥5 mm according to the family preference.
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Quistes , Niño , Quistes/cirugía , Humanos , Recién Nacido , Masculino , Estudios RetrospectivosRESUMEN
Bochdalek hernia (BH) is characterized by a defect of the posterolateral diaphragm and intrathoracic herniation of abdominal organs. The laparoscopic or thoracoscopic approach has recently become the surgical standard. However, studies on combined approaches are limited. An 8-year-old boy diagnosed with left BH was treated using a combined laparoscopic and thoracoscopic approach. On laparoscopy, BH with hernia sac was identified. Spleen, pancreas tail, kidney, and transverse colon had herniated into the left thoracic cavity. After the adhesion between transverse colon and hernia sac was dissected, all abdominal organs were restored to the abdominal cavity. On thoracoscopy, an 8 × 8 cm hernia orifice defect was identified and closed by suture. The postoperative course was uneventful, with no recurrence. A combined laparoscopic and thoracoscopic approach is safe and effective with a good field of view for left BH with hernia sac in children. To the best of our knowledge, this is the first case with left BH reporting the use of both approaches in a child without conversion.
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Hernias Diafragmáticas Congénitas , Laparoscopía , Niño , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Hernias Diafragmáticas Congénitas/cirugía , Humanos , Masculino , Toracoscopía , Tórax , Adherencias Tisulares/cirugíaRESUMEN
INTRODUCTION: In pediatric surgery, the umbilicus with humid environment prone to bacterial colonization has become the most common site of entrance into the peritoneum. However, the umbilical flora in children has never been reported. This study aimed to describe the characteristics of umbilical microflora in children before antiseptic skin preparation. PATIENTS AND METHODS: We prospectively reviewed all children (age, ≤ 15 years) undergoing surgical procedures using umbilical access between April 2020 and June 2021. Before antiseptic skin preparation, culture swabs were taken from the umbilicus. Data on age, sex, and surgical procedure as well as microflora results and clinical findings were analyzed. RESULTS: Overall, data on 123 children aged between 9 days and 15 years (median: 3 years) were obtained. In the umbilicus, the most frequent colonizing bacteria were coagulase-negative Staphylococcus species and Corynebacterium. The isolation of intestinal bacteria from children aged ≤ 3 years was significantly increased (P = 0.03). The results of the multidrug resistance test revealed that the bacteria from the umbilicus exhibited a high frequency of cefazolin (CEZ) resistance (46.1%). No postoperative surgical site infection was recorded in our study. CONCLUSIONS: This prospective study is the first report to investigate the umbilical microflora in over 100 children. In this study, a large spectrum of both resident and transient microflora was cultured from the umbilicus. This umbilical microflora was similar to previous reports of adult microflora except in children aged ≤ 3 years. Our data suggest that in children ≤ 3 years, preoperative and postoperative antibiotics should be chosen by considering CEZ resistance and intestinal bacteria. The result of umbilical microflora would be useful to select the antibiotics for treatment of surgical site infection (SSI), and the culture swabs from the umbilicus before the operation for the children at high risk for SSI are highly recommended.
Asunto(s)
Antiinfecciosos Locales , Ombligo , Abdomen , Adulto , Niño , Humanos , Estudios Prospectivos , Infección de la Herida Quirúrgica/epidemiología , Ombligo/cirugíaRESUMEN
BACKGROUND: Testicular appendage torsion (TAT) is a medical emergency that presents as an acute scrotum, usually in children and preadolescents. In previous reports of TAT, most cases have been treated conservatively, but some necessitate surgical treatment. Our aim was to examine the incidence, clinical examination findings, etiology, and treatment of TAT. METHODS: We retrospectively reviewed records of all patients with TAT (aged ≤15 years) treated at the Juntendo University Urayasu Hospital between January 2012 and September 2020. Surgical treatment was performed when a diagnosis of testicular torsion could not be completely ruled out or if pain recurred after conservative treatment. Patients with a hard scrotum or scrotal erythema were hospitalized for conservative treatment. Data regarding age, diagnosis, blood test results, and clinical findings were analyzed. RESULTS: Among 101 boys with TAT, the median age was 10 years. The incidence of TAT varied significantly according to age and was highest among patients aged 8-11 years. Sixty-seven boys (66.3%) underwent inpatient surgical treatment, 10 boys (9.9%) received inpatient conservative treatment, and 24 boys (23.8%) received outpatient conservative treatment. The median duration of hospitalization was significantly shorter among those who underwent surgery (2.0 days) than among those who received inpatient conservative treatment group (3.5 days). CONCLUSIONS: Operations were short, uncomplicated, and safe; they shortened the hospital stay; and they would certainly prevent recurrence of TAT and testicular torsion on one side. Furthermore, we recommended that TAT patients presenting with signs of severe inflammation, such as hard scrotum or scrotal erythema, receive early surgical treatment to minimize duration of hospitalization.
Asunto(s)
Epididimitis , Torsión del Cordón Espermático , Masculino , Niño , Humanos , Estudios Retrospectivos , Epididimitis/complicaciones , Epididimitis/diagnóstico , Epididimitis/terapia , Torsión del Cordón Espermático/diagnóstico , Torsión del Cordón Espermático/epidemiología , Torsión del Cordón Espermático/cirugía , Escroto/cirugía , Dolor/etiología , Enfermedad AgudaRESUMEN
We evaluated changes in the complement system resulting from anti-vascular endothelial growth factor (VEGF) in eyes with age-related choroidal neovascularization (CNV) including neovascular age-related macular degeneration, pachychoroid neovasculopathy, and polypoidal choroidal neovasculopathy. We measured the concentrations of the complement activation products (C3a, C4a), VEGF, and monocyte chemotactic protein-1 in the aqueous humor during intravitreal anti-VEGF injections for CNV. The VEGF level decreased significantly (P < 0.001), while the C3a and C4a levels increased significantly (P < 0.001 for both comparisons) 1 month after two monthly anti-VEGF injections. The VEGF level was correlated with the C3a (R = 0.328, P = 0.007) and C4a (R = - 0.237, P = 0.055) levels at baseline, but the correlation between the VEGF and C3a levels (R = - 0.148, P = 0.242) changed significantly (P = 0.028 by analysis of covariance) after anti-VEGF treatment. The C3a increase after anti-VEGF therapy did not change the visual outcomes in eyes with CNV for 1 year. Dysregulation of the complement system can be induced after anti-VEGF therapy.