Bevacizumab as a treatment for hereditary hemorrhagic telangiectasia in children: a case report

Case description: Five-year-old female patient with hereditary hemorrhagic telangiectasia.Clinical Findings: Deterioration of cardiopulmonary function with higher oxygen requirements secondary to pulmonary arteriovenous shunts, epistaxis.Treatment and Outcome: The patient was treated with the monoclonal antibody bevacizumab, which inhibits the vascular endothelial growth factor, with good clinical outcome.Clinical Relevance: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by arteriovenous malformations in different organs, making its clinical presentations varied. Systemic therapeutic options for a generalized disease are limited. The monoclonal antibody bevacizumab, seems to be a good option in this disorder. Although reported as successful in adult population, its use in pediatric population has not yet been reported. Here we report the use of bevacizumab in a 5-year-old female patient with hereditary hemorrhagic telangiectasia, showing clinical benefits and good outcome.

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Management of Refractory Gastrointestinal Bleeding in Hereditary Hemorrhagic Telangiectasia with Bevacizumab

Case Reports in Gastrointestinal Medicine ◽

10.1155/2021/2242178 ◽

2021 ◽

Vol 2021 ◽

pp. 1-4

Author(s):

Muaaz Masood ◽

Michael Coles ◽

Humberto Sifuentes

Keyword(s):

Monoclonal Antibody ◽

Gastrointestinal Bleeding ◽

Hereditary Hemorrhagic Telangiectasia ◽

Autosomal Dominant ◽

Vascular Malformations ◽

Vascular Endothelial ◽

Gi Bleeding ◽

Autosomal Dominant Disorder ◽

Recombinant Monoclonal Antibody ◽

Endothelial Growth Factor

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder resulting in vascular malformations of several organs including the pulmonary, cerebral, and gastrointestinal systems. One sequela is recurrent gastrointestinal (GI) bleeding. Bevacizumab (Bev) is emerging as an effective treatment of recurrent gastrointestinal bleeding in HHT. Bev is a recombinant monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), an integral part of angiogenesis.

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A Novel Missense Mutation in the Endoglin Gene in Hereditary Hemorrhagic Telangiectasia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655946 ◽

1997 ◽

Vol 77 (02) ◽

pp. 243-247 ◽

Cited By ~ 15

Author(s):

Hiroshi Yamaguchi ◽

Hiroyuki Azuma ◽

Toshio Shigekiyo ◽

Hideo Inoue ◽

Shiro Saito

Keyword(s):

Missense Mutation ◽

Hereditary Hemorrhagic Telangiectasia ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Autosomal Dominant Disorder ◽

Her Family ◽

Normal Individuals ◽

Oligonucleotide Hybridization ◽

Vascular Dysplasia ◽

Exon 4

SummaryHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystem vascular dysplasia and recurrent hemorrhage. Recent investigation has mapped one of the responsible genes for HHT to chromosome 9q33-q34; subsequently, nine different mutations have been identified in the endoglin gene, which encodes a transforming growth factor β(TGF-β) binding protein, in nine unrelated families with HHT. We examined the endoglin gene in a Japanese patient with HHT and her family members. Using PCR-SSCP. analysis followed by sequencing, we identified a C to A missense mutation in exon 4 which changed an Ala160 codon(GCT) to an Asp160 codon (GAT). Since this mutation destroys one of three Fnu4H I sites in exon 4, the Fnu4H I digestion patterns of the PCR-amplified exon 4 fragments from each family member were analyzed. In affected members, the restriction patterns were all consistent with a phenotype of HHT. PCR-amplified exon 4 fragments from 150 normal individuals were also analyzed by allele-specific oligonucleotide hybridization analysis. As a result, the mutation was not found in any of them. We conclude that the C to A mutation in exon 4 of the endoglin gene in this proband is responsible for the occurrence of HHT in this family.

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Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development, Characterization and Applications

Molecules ◽

10.3390/molecules26144127 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4127

Author(s):

Aline de Cristo Soares Alves ◽

Franciele Aline Bruinsmann ◽

Silvia Stanisçuaski Guterres ◽

Adriana Raffin Pohlmann

Keyword(s):

Monoclonal Antibody ◽

Physicochemical Characterization ◽

Vascular Endothelial ◽

Organic Nanoparticles ◽

Humanized Monoclonal Antibody ◽

Angiogenesis Process ◽

Endothelial Growth Factor ◽

Drug Pharmacokinetics

Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.

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Kaposiform Hemangioendothelioma: clinicopathological characteristics of 8 cases of a rare vascular tumor and review of literature

Diagnostic Pathology ◽

10.1186/s13000-021-01080-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Qurratulain Chundriger ◽

Muhammad Usman Tariq ◽

Jamshid Abdul-Ghafar ◽

Arsalan Ahmed ◽

Nasir Ud Din

Keyword(s):

Pediatric Population ◽

Adult Population ◽

Correct Diagnosis ◽

Kaposi Sarcoma ◽

Minor Component ◽

Vascular Tumor ◽

Giant Cells ◽

Clinicopathological Characteristics ◽

Multinucleated Giant Cells ◽

Kaposiform Hemangioendothelioma

Abstract Background Kaposiform Hemangioendothelioma (KHE) is a rare vascular tumor of intermediate malignant potential which shows locally aggressive growth but only rarely metastasizes. It is mostly considered to be a tumor of pediatric population but its occurrence in the adults is not uncommon as once considered. Histologically, KHE can mimic other soft tissue neoplasms of different behaviors (e.g. Kaposi Sarcoma, hemangioma) and establishing the correct diagnosis is important for appropriate treatment. Herein, we describe the clinicopathological features of 8 cases of KHE which will be helpful in making their diagnosis. Methods We reviewed pathology reports, microscopy glass slides and obtained follow up information about 8 cases of KHE which were diagnosed at our institution from January 2008 till June 2020. Immunohistochemical stain for HHV8 was also performed. Results Age ranged from 7 months to 25 years. Seven patients were less than 20 years of age and one patient was 25 years old. Equal gender distribution was observed. Extremities were the most common sites of involvement, followed by head and neck, pancreas and ischiorectal region. 2 cases were resection specimen and all others were incisional biopsies. The largest tumor size was 5.5 cm in one of the resections. The incisional/fragmented tissues were all less than 5 cm in aggregate. Most cases showed predominance of nodular growth and a minor component of spindle cell population along with lymphangiomatosis like vascular channels, with evidence of microthrombi in 2 cases. Few multinucleated giant cells were observed in 2 cases. None of the cases exhibited significant nuclear atypia or mitotic activity. One of the cases arising in dermis showed underlying bone involvement. HHV8 was negative in 7/7 cases. Conclusions KHE can also involve adult population and it should always be considered in the differential diagnoses of a vascular lesion. Presence of multinucleated giant cells is a rare finding. Knowledge about histological features and potential mimics is helpful in avoiding misdiagnosis.

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Choroidal neovascular membrane in paediatric patients: clinical characteristics and outcomes

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-310497 ◽

2017 ◽

Vol 102 (9) ◽

pp. 1232-1237 ◽

Cited By ~ 2

Author(s):

Tapas Ranjan Padhi ◽

Bradley J Anderson ◽

Ashkan M Abbey ◽

Yoshihiro Yonekawa ◽

Maxwell Stem ◽

...

Keyword(s):

Clinical Characteristics ◽

Adult Population ◽

Initial Therapy ◽

Macular Dystrophy ◽

Vascular Endothelial ◽

Fluorescein Angiogram ◽

Anti Vegf ◽

Treatment Indications ◽

Endothelial Growth Factor

PurposeTo analyse the clinical characteristics and treatment outcomes of choroidal neovascular membranes (CNVM) in paediatric subjects at three paediatric retina referral centres.MethodsMedical charts of patients aged 18 years or less with a diagnosis of CNVM were retrospectively reviewed. The demographic profile, laterality, presenting complaint, corrected vision, underlying pathology, fundus, fundus fluorescein angiogram and optical coherence tomogram (OCT) were analysed. CNVM type, frequency, treatment indications, recurrences and final visual acuity were noted.ResultsThere were a total of 35 subjects (43 eyes) with a mean age of 11.2 years. The CNVMs were mostly type 2 (90.0%), classic (90.9%), subfoveal (59.09%) and active (84.1%). Best vitelliform macular dystrophy was found to be the most common association (32.5%). Intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent was the initial therapy of choice in all. Eyes with CNVMs responsive to anti-VEGF alone required a mean of 2.11 injections. Patients with recurrent disease (21.21%) had an average of 1.14 episodes per eye. While 50% of recurrent CNVMs stabilised with repeat anti-VEGF treatment, the remaining patients required photodynamic therapy, laser or surgery.ConclusionPaediatric CNVMs in this series differed from those in the adult population with regard to aetiology, OCT and angiographic characteristics, treatment response and rate of recurrence.

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Therapeutic Management of a Substantial Pelvic Aneurysmatic Bone Cyst Including the Off-Label Use of Denosumab in a 35-Year-Old Female Patient

Case Reports in Orthopedics ◽

10.1155/2017/9125493 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5

Author(s):

D. Ntalos ◽

M. Priemel ◽

C. Schlickewei ◽

D. M. Thiesen ◽

J. M. Rueger ◽

...

Keyword(s):

Monoclonal Antibody ◽

Female Patient ◽

Therapeutic Agent ◽

Surgical Intervention ◽

Case Reports ◽

Bone Cyst ◽

Off Label Use ◽

Aneurysmal Bone Cysts ◽

Promising Therapeutic Agent

Aneurysmal bone cysts (ABC) are benign bone tumors, which are highly vascularized. The main course of treatment is curettage followed by bone grafting or cement insertion. Still recurrence remains a main problem for patients. Denosumab is a monoclonal antibody, which acts as an inhibitor of the RANK/RANKL pathway, diminishing bone turnover. Recent case reports have shown that Denosumab can be a promising therapeutic agent for people suffering from therapy-resistant ABC. We report the case of a 35-year-old female patient presenting with a pronounced ABC of the pelvis. Since the tumor was inoperable, Denosumab was administered, leading to a significant shrinkage of the lesion, which allowed surgical intervention. Upon recurrence, Denosumab was restarted putting the patient once more into remission. Follow-up was four years overall with a clinical and radiological stable disease for fifteen months after final discontinuation of the monoclonal antibody. Therefore, our case further underlines the potential of Denosumab in the treatment of ABC.

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Pediatric Lung Transplantation: Perspectives for the Pathologist

Pediatric and Developmental Pathology ◽

10.2350/07-09-0347.1 ◽

2008 ◽

Vol 11 (2) ◽

pp. 85-105 ◽

Cited By ~ 3

Author(s):

Megan K. Dishop ◽

George B. Mallory ◽

Frances V. White

Keyword(s):

Lung Transplantation ◽

Pediatric Population ◽

Adult Population ◽

Bronchiolitis Obliterans Syndrome ◽

Pulmonary Vascular Disease ◽

Pathologic Evaluation ◽

Routine Surveillance ◽

Pediatric Pathologist ◽

Future Challenges ◽

Cellular Rejection

Lung transplantation offers life-saving and life-extending treatment for children and adolescents with congenital and acquired forms of pulmonary and pulmonary vascular disease, for whom medical therapy is ineffective or insufficient for sustained response. This review summarizes the pathology related to lung transplantation for the practicing pediatric pathologist and also highlights aspects of lung transplantation unique to the pediatric population. Clinical issues related to availability of organs, candidate eligibility, surgical technique, and postoperative monitoring are discussed. Pathologic evaluation of routine surveillance transbronchial biopsies requires attention to acute cellular rejection, opportunistic infection, and other forms of acute and resolving lung injury. These findings are correlated in some cases with endobronchial biopsies and bronchoalveolar lavage as adjunctive tools in surveillance. Open or thoracoscopic biopsies also have diagnostic utility in cases with acute or chronic graft deterioration of uncertain etiology. Future challenges in pediatric lung transplantation are similar to those in the adult population, with continued efforts focused on prolonging graft survival, prevention of bronchiolitis obliterans syndrome due to chronic cellular rejection, and evaluation of humoral rejection.

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MR-Proadrenomedullin as biomarker of renal damage in urinary tract infection in children

BMC Pediatrics ◽

10.1186/s12887-021-02765-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Rafael Peñalver Penedo ◽

Marta Rupérez Lucas ◽

Luis Antonio Álvarez-Sala Walther ◽

Alicia Torregrosa Benavent ◽

María Luisa Casas Losada ◽

...

Keyword(s):

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Pediatric Patients ◽

Pediatric Population ◽

Adult Population ◽

Roc Curves ◽

Renal Scintigraphy ◽

Reactive Protein ◽

Sensitivity Specificity

Abstract Background Midregional-proadrenomedullin (MR-proADM) is a useful prognostic peptide in severe infectious pathologies in the adult population. However, there are no studies that analyze its utility in febrile urinary tract infection (fUTI) in children. An accurate biomarker would provide an early detection of patients with kidney damage, avoiding other invasive tests like renal scintigraphy scans. Our objective is to study the usefulness of MR-proADM as a biomarker of acute and chronic renal parenchymal damage in fUTI within the pediatric population. Methods A prospective cohort study was conducted in pediatric patients with fUTI between January 2015 and December 2018. Plasma and urine MR-proADM levels were measured at admission in addition to other laboratory parameters. After confirmation of fUTI, renal scintigraphy scans were performed during the acute and follow-up stages. A descriptive study has been carried out and sensitivity, specificity and ROC curves for MR-proADM, C-reactive protein, and procalcitonin were calculated. Results 62 pediatric patients (34 female) were enrolled. Scintigraphy showed acute pyelonephritis in 35 patients (56.5%). Of those patients, the median of plasmatic MR-proADM (P-MR-proADM) showed no differences compared to patients without pyelonephritis. 7 patients (11.3%) developed renal scars (RS). Their median P-MR-proADM levels were 1.07 nmol/L (IQR 0.66–1.59), while in patients without RS were 0.48 nmol/L (0.43–0.63) (p < 0.01). The AUC in this case was 0.92 (95% CI 0.77–0.99). We established an optimal cut-off point at 0.66 nmol/L with sensitivity 83.3% and specificity 81.8%. Conclusion MR-ProADM has demonstrated a poor ability to diagnose pyelonephritis in pediatric patients with fUTI. However, P-MR-proADM proved to be a very reliable biomarker for RS prediction.

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High frequency of otolaryngology/ENT encounters in Canadian primary care despite low medical undergraduate

Canadian Medical Education Journal ◽

10.36834/cmej.72328 ◽

2021 ◽

Author(s):

Brendan Sorichetti ◽

Julie Pauwels ◽

Thomas Jacobs ◽

Neil Chadha ◽

Emelie Kozak ◽

...

Keyword(s):

Primary Care ◽

Medical Students ◽

Primary Care Physicians ◽

Pediatric Population ◽

Adult Population ◽

Care Facility ◽

Symptom Presentation ◽

Undergraduate Medical Students ◽

Related Symptom ◽

Medical Undergraduate

Otolaryngology involves the treatment of patients with diseases and disorders of the ear, nose, throat (ENT), and related structures of the head and neck. Many medical students in Canada have limited experiences in ENT and a vast majority of these students go on to pursue a career as primary care physicians. Physicians at a primary care facility classified patient’s visits as either being “ENT” related or not, to assess the amount of ENT related concerns they typically encounter. The data was collected separately in the summer and winter months to assess any seasonal variability. One in eight patient encounters presented with an ENT related concern. The percentage of ENT related symptom presentation visits in the pediatric population for both data collection periods (29%) was more than three times that of the adult population (9%). The rate of ENT symptom presentation in both adult and pediatric populations was not affected by seasonality. Primary care physicians will encounter new patients presenting with ENT related concerns quite frequently. This is especially true in the pediatric patient population. Increased ENT medical education is both necessary and essential for undergraduate medical students, residents, and primary care physicians.

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Primary Cardiac Fibroma in an Adult

Case Reports in Cardiology ◽

10.1155/2015/713702 ◽

2015 ◽

Vol 2015 ◽

pp. 1-3

Author(s):

Samuel H. Cho ◽

Timothy Fritz ◽

Lynn J. Cronin ◽

Stephen D. Cohle

Keyword(s):

Connective Tissue ◽

Left Ventricle ◽

Pediatric Population ◽

Adult Population ◽

Surgical Excision ◽

Imaging Modalities ◽

Cardiac Fibroma ◽

Primary Tumors ◽

Immunohistological Analysis ◽

Unusual Finding

Cardiac fibromas are benign primary tumors composed of connective tissue and fibroblasts. These uncommon tumors are primarily found in the pediatric population, and their prevalence among the adult population is exceedingly rare. We report a case of an adult with nonspecific symptoms, who was subsequently found to have a solitary mass located in the left ventricle. This case highlights an unusual finding in an adult who through various imaging modalities, surgical excision, and immunohistological analysis was found to have a cardiac fibroma.

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