Episodes Of Swelling Research Articles

Prolonging the circulatory half-life of C1 esterase inhibitor via albumin fusion.

Hereditary Angioedema (HAE) is an autosomal dominant disease characterized by episodic swelling, arising from genetic deficiency in C1-esterase inhibitor (C1INH), a regulator of several proteases including activated Plasma kallikrein (Pka). Many existing C1INH treatments exhibit short circulatory half-lives, precluding prophylactic use. Hexahistidine-tagged truncated C1INH (trC1INH lacking residues 1-97) with Mutated N-linked Glycosylation Sites N216Q/N231Q/N330Q (H6-trC1INH(MGS)), its murine serum albumin (MSA) fusion variant (H6-trC1INH(MGS)-MSA), and H6-MSA were expressed in Pichia pastoris and purified via nickel-chelate chromatography. Following intravenous injection in mice, the mean terminal half-life of H6-trC1INH(MGS)-MSA was significantly increased versus that of H6-trC1INH(MGS), by 3-fold, while remaining ~35% less than that of H6-MSA. The extended half-life was achieved with minimal, but significant, reduction in the mean second order rate constant of Pka inhibition of H6-trC1INH(MGS)-MSA by 33% relative to that of H6-trC1INH(MGS). Our results validate albumin fusion as a viable strategy for half-life extension of a natural inhibitor and suggest that H6-trC1INH(MGS)-MSA is worthy of investigation in a murine model of HAE.

Novel mutation in XPNPEP3 in a patient with heart failure without nephronophthisis-like nephropathy (NPHPL1): case report and literature review

Background X-prolyl aminopeptidase 3(XPNPEP3) mutations are known to cause nephronophthisis-like nephropathy-1 (NPHPL1), a rare autosomal-recessive kidney disease characterized by progressive kidney failure and cystic kidney disease in childhood. The full phenotypic spectrum associated with mutations in XPNPEP3 is not fully elucidated.Case presentationA 13-year-old Chinese female patient with intellectual disability presented with a 2-year history of convulsions and fatigue, with a recent episode of swelling, breathlessness, and nocturnal dyspnea lasting 10 days. The patient was diagnosed with heart failure and kidney failure. Whole exome sequencing revealed a homozygous c.970–2 A > G mutation in XPNPEP3 associated with severe cardiac dysfunction and neurological symptoms, including epilepsy and intellectual disability. Notably, kidney ultrasound did not reveal the typical changes of NPHPL1, and kidney failure was hypothesized to be secondary to cardiac dysfunction rather than primary kidney pathology.ConclusionsThis case suggests the possible association of additional phenotypic features associated with XPNPEP3 mutations, emphasizing the need for further investigation into the heterogeneous clinical presentations associated with XPNPEP3 mutations. The findings highlight the importance of considering alternative phenotypes in patients with genetic mutations traditionally associated with specific diseases. Segregation and functional analyses are necessary to determine causality between the c.970–2 A > G XPNPEP3 mutation and disease.

Initial Experience of Long-Term Prophylaxis with Lanadelumab for Hereditary Angioedema in China: A Clinical Observation Study on Six Patients

Plain Language SummaryHereditary angioedema (HAE) is a rare genetic disease characterized by recurring episodes of painful swelling of the subcutaneous and submucosal tissue, and its pathogenesis is due to the deficiency or dysfunction C1-esterase inhibitors. HAE attacks can affect many areas of the body, but most frequently involve the extremities, gastrointestinal tract, genitals, face, and upper airway. Swelling of the larynx can occur, with potentially fatal consequences owing to asphyxiation. Since 2020, China has had the only first-line treatment drug that can prevent HAE attacks – lanadelumab. Our study evaluated the efficacy and safety of lanadelumab by observing the 6 patients in China mainland who were the first to use it. Our research showed that lanadelumab can prevent the attack of HAE, greatly improve the quality of life of patients, and has good safety. A reasonable dosage plan can ensure stable therapeutic effects of lanadelumab. In addition, the efficacy of lanadelumab remained stable during COVID-19 vaccination and infection.

Parotite ricorrente giovanile: inquadramento clinico e approccio diagnostico-terapeutico

Juvenile recurrent parotitis is an uncommon condition characterised by recurrent episodes of parotid swelling that affects school-aged and pre-school children and shows a typical tendency to self-resolution during adolescence. To date, etiopathogenetic hypotheses and treatment options are still debated, as there are no current guidelines for its diagnosis and treatment so far. This article aims to provide valid recommendations for the management of children with recurrent episodes of parotitis and tips to identify cases worthy of further investigation and referral to the specialist.

Long term outcome of C1-esterase inhibitor deficiency.

Hereditary angioedema (HAE) is a rare hereditary disorder characterized by episodic swelling and life-threatening airway obstruction caused by laryngeal angioedema. In most HAE patients, reduced level of serum C1-Inhibitor (type-I-HAE) or presence of aberrant C1-Inhibitor (type-II-HAE) result in the lost of regulation of the complementary system and contact activation system with downstream over-activation of bradykinin - the chief mediator leading to angioedema. Type-III HAE (HAE-nl-C1INH) is rare without deficient or dysfunction of C1-Inhibitor, often with genetic aberrant related to the contact activation system. The prevalence of HAE in the population is estimated at 1 in 50,000 individuals, often with early onset, but due to the heterogeneity of the disease, there is frequently a significant delay in diagnosis. Recently, better awareness by physicians, more access to diagnostic tools, better management and prophylaxis has decreased morbidity and mortality. A focus in HAE patient care shift from management of attacks with on-demand medication, to use of prophylaxis to reduce attacks has improved the overall quality of life of patients with HAE. One area in HAE research that has not been emphasized is the long-term consequence of C1-INH deficiency in HAE patients, other than the typical manifestations of HAE, as evidence have emerged linking this disorder with increased risk of cardiovascular diseases, auto-immune disorders, and malignancy. This review aims to gather the current knowledge and evidence of potential consequence of C1-Inhibitor deficiency in HAE aside from angioedema with emphasis in the improvement of long-term care and overall quality of life for HAE patients.

Delayed Hypersensitivity Reaction to Dermal Fillers Following mRNA COVID-19 Vaccination

Dear Editor, I wish to bring attention to a potential delayed immune reaction associated with dermal fillers in the context of mRNA COVID-19 vaccines. While severe vaccine reactions remain uncommon, the widespread administration of mRNA vaccines and the prevalent use of dermal fillers necessitate a closer examination of their possible interactions. We recently encountered a 59-year-old female patient who developed persistent facial swelling months after receiving the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine. Notably, the patient had a history of dermal filler injections, predominantly hyaluronic acid, administered three to four years prior. Despite various therapeutic interventions, including antihistamines, corticosteroids, and ACE inhibitors, she experienced recurrent episodes of swelling. Ultrasound assessment revealed the absence of residual filler material, leading us to consider an immune-mediated response potentially triggered by the mRNA vaccine. This case highlights the importance of further research into the interaction between mRNA COVID-19 vaccines and dermal fillers. It suggests that individuals with a history of dermal fillers may be susceptible to delayed inflammatory reactions post-vaccination. Clinicians should be aware of this potential adverse event, particularly when evaluating patients with unexplained facial swelling following vaccination.

Centralized care model for hereditary angioedema overcomes geographical barriers.

Hereditary angioedema due to C1 inhibitor deficiency (HAE) is a rare inborn error of immunity that presents with episodic swelling. Management is multifaceted and includes on-demand treatment of swelling episodes, short-term prophylaxis to prevent swelling episodes from procedures, and long-term prophylaxis (LTP) to prevent angioedema on an ongoing basis. All approved on-demand therapies are parenteral, necessitating patient training for home administration, particularly intravenous C1 inhibitor. These complexities can result in care gaps for rural HAE patients. We conducted a cross-sectional study at our Angioedema Center of Reference and Excellence to assess the care provided to urban and rural patients. The proportion of patients receiving LTP, proportion of patients diagnosed as children, and disease control measured using the Angioedema Control Test (AECT) were collected. Logistic and Poisson regression models adjusted for age and sex were used to compare the two groups. The proportion using LTP was similar at 62% and 61% in urban and rural patients, respectively (odds ratio [OR] 1.01 (CI 95% 0.34-2.99)). Among urban patients, 52% were diagnosed as children compared to 60% among rural residents (1.43 (0.37-5.56)). The mean (IQR) AECT score was 14.0 (8.5-15.5) in urban patients and 13.0 (10.0-14.0) in rural patients (Poisson β -0.001 (-0.23-0.23). These data indicate that rural patients received similar high-quality care. We attribute these findings to the centralized care model employed in which HAE patients in the region are seen at a single comprehensive care clinic.

Global, regional, and national burden of gout, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Gout is an inflammatory arthritis manifesting as acute episodes of severe joint pain and swelling, which can progress to chronic tophaceous or chronic erosive gout, or both. Here, we present the most up-to-date global, regional, and national estimates for prevalence and years lived with disability (YLDs) due to gout by sex, age, and location from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, as well as forecasted prevalence to 2050. Gout prevalence and YLDs from 1990 to 2020 were estimated by drawing on population-based data from 35 countries and claims data from the USA and Taiwan (province of China). Nested Bayesian meta-regression models were used to estimate prevalence and YLDs due to gout by age, sex, and location. Prevalence was forecast to 2050 with a mixed-effects model. In 2020, 55·8 million (95% uncertainty interval 44·4-69·8) people globally had gout, with an age-standardised prevalence of 659·3 (525·4-822·3) per 100 000, an increase of 22·5% (20·9-24·2) since 1990. Globally, the prevalence of gout in 2020 was 3·26 (3·11-3·39) times higher in males than in females and increased with age. The total number of prevalent cases of gout is estimated to reach 95·8 million (81·1-116) in 2050, with population growth being the largest contributor to this increase and only a very small contribution from the forecasted change in gout prevalence. Age-standardised gout prevalence in 2050 is forecast to be 667 (531-830) per 100 000 population. The global age-standardised YLD rate of gout was 20·5 (14·4-28·2) per 100 000 population in 2020. High BMI accounted for 34·3% (27·7-40·6) of YLDs due to gout and kidney dysfunction accounted for 11·8% (9·3-14·2). Our forecasting model estimates that the number of individuals with gout will increase by more than 70% from 2020 to 2050, primarily due to population growth and ageing. With the association between gout disability and high BMI, dietary and lifestyle modifications focusing on bodyweight reduction are needed at the population level to reduce the burden of gout along with access to interventions to prevent and control flares. Despite the rigour of the standardised GBD methodology and modelling, in many countries, particularly low-income and middle-income countries, estimates are based on modelled rather than primary data and are also lacking severity and disability estimates. We strongly encourage the collection of these data to be included in future GBD iterations. Bill & Melinda Gates Foundation and the Global Alliance for Musculoskeletal Health.

Insulin-induced Lipohypertrophy in a Patient with Type 2 Diabetes

Abstract Lipohypertrophy (LH) is a common side effect of insulin treatment in patients with diabetes, characterized by soft, benign nodules in the subcutaneous tissue. This case report describes the management of insulin-induced LH in a 66-year-old male with type 2 diabetes. The patient had been on a combination of oral antidiabetic agents (ODAs) and biphasic human insulin for 5 years, experiencing the symptoms of numbness, leg swelling, fatigue, and frequent hypoglycemic episodes. Upon examination, LH with skin pigmentation was observed at the insulin injection sites on both calves. The patient’s laboratory investigations revealed poor glycemic control with high glycated hemoglobin percentage. To address the condition, the patient was advised to change the injection site, use proper site rotation, and change the insulin needle daily. The insulin therapy was modified by switching to biphasic premixed analog insulin injected 5 min before meals using the insulin pen. In addition, ODAs were adjusted for better glycemic control. Following these interventions, the patient reported improved glucose levels and stable kidney function. This case report emphasizes the importance of early detection and appropriate management of insulin-induced LH through patient education and insulin therapy adjustments. Health-care providers should remain vigilant for LH and educate patients on proper injection practices to optimize diabetes management and prevent complications.

Internal Jugular Vein Phlebectasia with Situs Inversus Totalis: A Rare Association in a Child

Background: Phlebectasia is a term used for the dilatation of a vein without tortuosity. Rarely, the condition may affect the internal jugular vein (IJV), causing prominence in the neck, which may be confused with other neck swellings. Clinical Description: A 6-year-old boy presented with bilateral episodic swelling in the neck noticed since 2 years of age and a hoarse voice since 3 years of age. On examination, the neck swelling was soft, cystic, compressible, nontender, and nonpulsatile, increasing in size by all maneuvers increasing intrathoracic pressure. Systemic examination revealed the apex beat was on the right side, and the liver was palpable below the left subcostal margin. Management and Outcome: The workup for tuberculosis was negative, and direct laryngoscopy was normal. X-ray of the chest with abdomen showed dextrocardia and stomach shadow on the right side. Color Doppler revealed nontortuous dilatation of both IJVs. Dynamic computed tomography venography confirmed the diagnosis of bilateral IJV phlebectasia (IJVP). The child was started on speech therapy. The mother was counseled regarding the benign nature of the disease and advised regular follow-up. The child had no complications, and his voice improved with speech therapy at 1-year follow-up. Conclusion: Pediatricians should be aware that IJVP may rarely be the cause of neck swelling associated with hoarseness of voice. Increase in the size of the swelling with Valsalva maneuvers and color Doppler ultrasound helps to confirm the diagnosis.

The effects of garetosmab in people with fibrodysplasia ossificans progressiva (FOP): A plain language summary of the LUMINA-1 study

What is this summary about? This is a plain language summary of a clinical research study called LUMINA-1. This study investigated a medicine called garetosmab in adults with fibrodysplasia ossificans progressiva, or FOP. FOP is a very rare disease that causes new bone to form in places where it does not usually develop (also known as heterotopic ossification). In FOP, when bone is formed in areas it is not supposed to, it results in mature heterotopic bone. The build-up of new bone makes it difficult for people with FOP to move, which means they often require the use of a wheelchair or other mobility aid. People with FOP who took part in the study were experiencing bone formation in areas where new bone should not form, flare-ups (episodes of localized swelling, pain, and/or warmth), and worsening joint movement. What were the results? People with FOP were given garetosmab or placebo every 4 weeks as a liquid infusion through a vein for 28 weeks. After 28 weeks, those who were receiving placebo were switched to garetosmab and treated for 28 weeks. This part was known as the open-label portion of the trial, which is when all people received garetosmab treatment. Treatment with garetosmab did not change the mature heterotopic bone in people with FOP, but it did stop new bone lesions from forming in areas where they should not. Treatment with garetosmab also reduced the number of flare-ups. During the trial, common side effects were nosebleeds, loss of eyebrows or eyelashes, and skin and soft tissue infections. Five people died during the open-label portion of the trial, when all were on garetosmab. Their deaths appeared consistent with the known causes of death and life expectancy of people with FOP who were of a similar age and severity of disease. There was no clear pattern that linked the deaths with how garetosmab works. However, a causal relationship between deaths and garetosmab could not be ruled out. What do the results of the study mean? The LUMINA-1 study showed that in people with FOP, garetosmab stopped new heterotopic bone from developing in areas that it should not and also reduced flare-ups. This shows that garetosmab may be a useful treatment for people with FOP. More testing is needed to better understand the benefits and risks of garetosmab. Clinical Trial Registration: NCT03188666 ( ClinicalTrials.gov ) (LUMINA-1)

Complex MEFV and MVK Variations in a Syrian Child: Implications for Clinical Phenotypes and Treatment Response-A Case Report.

This case report presents a 10-year-old Syrian boy with concurrent mutations in the Mediterranean fever (MEFV) and mevalonate kinase (MVK) genes, resulting in overlapping symptoms of Familial Mediterranean Fever (FMF) and Hyperimmunoglobulinemia D syndrome (HIDS), both classified as Periodic Fever Syndromes (PFSs). The co-occurrence of these mutations within a single individual is highly unusual. He presented with pallor, intermittent fever, and recurrent respiratory infections from an early age, along with anemia, splenomegaly, hepatomegaly, cervical lymphadenopathy, and growth failure noted in initial investigations. Still's disease was initially considered as the most likely differential diagnosis, leading to the initiation of treatment with methylprednisolone; however, the parents did not follow-up with the treatment. The child returned at 5 years old with appendicitis, which was surgically removed, and parents reported recurrent episodes of arthralgia and joint swelling accompanied by nearly daily fever. Although the child experienced delayed motor development, his cognitive abilities were normal. Genetic analysis identified a homozygous likely pathogenic variant in the MVK gene and a heterozygous likely pathogenic variant in the MEFV gene. The child remains reliant on corticosteroids, with limited response to colchicine and improvement noted after transitioning from tocilizumab to infliximab. The latest follow-up demonstrated significant improvement with no fever, joint swelling, or lymphadenopathy; however, signs of growth failure persist. The atypical manifestations observed in this case may indicate a synergistic effect between the 2 mutations, contributing to the overall clinical picture. Therefore, although HIDS may dominate the clinical presentation, we cannot entirely dismiss the possibility that the FMF mutation plays a role in modulating these symptoms.

Hereditary angioedema with normal C1 inhibitor associated with carboxypeptidase N deficiency

BackgroundHereditary angioedema (HAE) is a potentially life-threatening disorder characterized by recurrent episodes of subcutaneous or submucosal swelling. HAE with normal C1 Inhibitor (HAE-nC1-INH) is an under-diagnosed condition. Although the association with genetic variants has been identified for some families, the genetic causes in many patients with HAE-nC1-INH remain unknown. The role of genes associated with bradykinin catabolism is not fully understood. ObjectiveWe investigated the biological parameters and the genes related to kallikrein-kinin system (KKS) in families with a clinical phenotype of HAE-nC1-INH and presenting with a carboxypeptidase N (CPN) deficiency. MethodsThis study includes four families presenting with HAE-nC1-INH and CPN deficiency. Patients’ clinical records were examined, biological parameters of KKS measured, genetics was analyzed by next-generation sequencing and Sanger sequencing. Predictive algorithms (HSF®, SIFT®, Polyphen-2®, MutationTaster®, ClinPred®) were used to classify variants as affecting splicing, as benign to deleterious, or as disease-causing. ResultsPatients presented with angioedema and urticaria, mainly on face/lips, but also with abdominal pain or laryngeal symptoms. Affected patients displayed low CPN activity –30 to 50% of median value in plasma. We identified three variants of the CPN1 gene encoding the catalytic 55-kDa subunit of CPN at: c.533G>A, c.582A>G and c.734C>T. CPN deficiency associated with genetic variants segregated with HAE-nC1-INH symptoms in affected family members. ConclusionsCPN1 gene variants are associated with CPN deficiency and HAE-nC1-INH symptoms in four unrelated families. Genetic CPN deficiency may contribute to bradykinin and anaphylatoxins accumulation, with synergistic effects in angioedema and urticarial symptoms.

Arteriovenous malformation of quadriceps tendon

Abstract Objective: There have been few reported cases of muscle arteriovenous malformations in the literature to date. Case Report: We present the case of a 24-year-old male with an arteriovenous malformation involving the quadriceps tendon, presenting with recurrent episodes of pain and swelling in the right knee. The patient was treated with selective embolization of feeding arteries to the tumor, followed by surgical excision of the mass, and showed resolution of symptoms at 1 month follow-up. Conclusion: Selective embolization of the feeding artery results in the reduction of the tumor mass, and excision of the tumor becomes bloodless, easy, and safe.

Epidemiology and treatment of children with hereditary angioedema in Germany: A retrospective database study.

Hereditary angioedema (HAE) is a potentially life-threatening inherited disease that causes recurrent, serious, and debilitating episodes of swelling. While evidence has improved in adult patients, data on the epidemiology and treatment of pediatric patients with HAE remain very limited. The aim of this study was to determine the incidence and prevalence of pediatric patients with HAE aged <12years, as well as treatment patterns, co-medication, and specialties involved. In this retrospective study (2016-2021), the German IQVIATM pharmacy claims (LRx) database was used to analyze prescriptions of HAE-specific treatments and co-medications. We found an HAE prevalence in pediatric patients aged <12years of 2.51:100,000 and a 12-month prevalence of up to 1.02:100,000 between 2016 and 2021. Most HAE treatments were prescribed by outpatient clinics and pediatricians, with an increasing proportion of icatibant as an on-demand treatment and low rates of long-term prophylaxis (LTP). The prescription rate of analgesics as the most common co-medication decreased notably after HAE diagnosis. Our findings provide insights into the epidemiology and current pediatric HAE treatment landscape in Germany. The obtained HAE prevalence in pediatric patients aged <12years was even higher than the previously reported average of overall cohorts, whereas the LTP rate was low, which might indicate an unmet need for newer LTP treatment options in pediatric patients.

Evolution of Guidelines for the Management of Hereditary Angioedema due to C1 Inhibitor Deficiency.

Hereditary angioedema (HAE) is a severe and disabling condition characterized by recurrent episodes of subcutaneous or mucosal swelling in the skin and respiratory and gastrointestinal tracts. HAE due to C1-esterase inhibitor deficiency (C1-INH-HAE) is the most prevalent subtype. The present Iberian study compared C1-INH-HAE treatment guidelines published between 2010 and 2022 to identify the main differences in therapeutic approaches for on-demand treatment and short- and long-term prophylaxis (LTP). HAE guidelines evolved with the availability of new treatments and with a change in the management paradigm towards an individualized, patient-centered approach, where quality of life (QOL) is central. A parallel trend was observed towards increasingly frequent home-based treatment, which potentially facilitates timely interventions, provides greater flexibility and convenience, and is associated with increased QOL, enabling patients to lead more normal lives. Most innovations over the years were made for LTP, together with the advent of new therapies and awareness of patients' needs. Several prophylactic therapies with a high level of evidence became available, although formal head-to-head comparisons are lacking. The treatment goals became more ambitious, ranging from a reduction in the frequency, severity, and duration of attacks to achieving total disease control and normalization of patients' lives. The document also addresses relevant items such as changes in terminology (eg, the introduction of designations as "first-line") and the introduction of patient-reported outcome measures to assess patients' perceptions of their self-experienced QOL and well-being. Unmet needs in the management of C1-INH-HAE are identified.

FRI503 HCG-induced And Autoimmune Hyperthyroidism In A Male Patient With HCG Secreting Germ Cell Tumor

Abstract Disclosure: A.H. Mohamed: None. M. Basina: None. Background: While Graves’ disease is the most common cause of hyperthyroidism, other rare causes include HCG secreting germ cell tumors. We describe a hyperthyroidism case with metastatic HCG secreting germ tumor and Graves’ disease. Case: 34 years old smoker male presented in 2016 with weakness and hypokalemia 2.7 mmol/L with concerns of paroxysmal periodic paralysis and was found to have hyperthyroidism consistent with Graves’ disease per work up (suppressed TSH &amp;lt;0.01- uIU/ml (ref 0.27-4.2 uIU/ml), elevated FT4 4.08 ng/dl (ref 0.93-1.7 ng/dl), elevated Free T3 15.0 (ref 2.3 - 4.0 pg/ml), and (thyroid stimulating immunoglobulin (TSI) 354 (ref 0 - 139 %). He was started on methimazole 20 mg that he did not use and lost follow up. In May 2022, he presented with expressive aphasia and seizures along with 4 months of right scrotal swelling, generalized lymphadenopathy, and hemoptysis episodes. He had intermittent palpitations, 30 Ibs weight loss and eye bulging. On exam he was tachycardic 120 bpm, enlarged thyroid, brisk reflexes and mild tremors. His eye exam was significant for stare, lid lag, proptosis and bilateral lid edema. His labs were remarkable for suppressed TSH &amp;lt;0.01 uIU/ml, FT4 &amp;gt;7.7 ng/dl , Total T3 394 ng/dl (80 - 200 ng/dl)Thyrotropin receptor antibodies (TRAb) 29 IU/L (ref 0-1.75 IU/L), TSI 4.8 (ref &amp;lt;1.3 index), Thyroglobulin Ab 5.8 IU/ml (ref &amp;lt;4IU/ml), TPO-Ab &amp;gt;900 (ref &amp;lt;9.0) and HCG &amp;gt;1,000,000 (ref &amp;lt;2mIU/ml). Thyroid US showed diffuse heterogeneous enlargement of the thyroid with increased vascularity and without a discrete well-defined nodule. His lymphadenopathy work revealed high grade stage III C non-seminomatous mixed germ tumors (60% teratoma and 40% choriocarcinoma) with metastasis to brain, lungs, liver, spine, iliac and sacral bones. He was started on methimazole (MMI) 20 mg TID, propranolol 40 mg TID, dexamethasone 2 mg q6hrs and chemotherapy. His thyroid labs improved in 3 days to FT4 2.83 ng/dl and TT3 93 ng/dl while TSH and HCG were unchanged. He was discharged on MMI 25 mg daily. Over 3 months, he subsequently underwent right orchiectomy, cyber knife radiation of the brain metastatic lesions and 4 chemotherapy cycles. His HCG levels fluctuated (1,000,000-&amp;gt;3980-&amp;gt; 120,181) as well thyroid function test (TSH &amp;lt;0.01-&amp;gt; 5.1-&amp;gt;0.01 uIU/ml, FT4 1.02-&amp;gt;0.65-&amp;gt;5.7 ng/dl and TSI 6.4 ). He required multiple methimazole adjustments. Discussion: Co-occurrence of HCG secreting germ tumors and Graves’ hyperthyroidism is rare. HCG can bind TSH receptors and in high levels has thyrotropic effects. The interplay between HCG thyrotropic effects and thyroid autoimmunity can be challenging and use of both binding and functional bioassays maybe helpful. Close thyroid function monitoring and frequent adjustment of thioamides are needed as patients undergo treatment of the primary HCG source as well as long term follow up. Presentation: Friday, June 16, 2023

Hereditary angioedema in older adults: Understanding the patient perspective

BackgroundHereditary angioedema (HAE) is a rare condition characterized by potentially fatal, recurrent episodes of painful swelling. Whereas there are limited studies evaluating the quality of life of individuals with HAE, none have evaluated the impact of HAE on older adults. ObjectiveTo evaluate the effect of HAE on older adults through qualitative methodology. MethodsA group of 3 physicians with extensive research and clinical experience in HAE developed a focus group guidebook highlighting issues of importance to older adults. A total of 17 patients with HAE (type I or II) aged 60 years and older participated in focus groups. Three independent reviewers coded each focus group transcript using a thematic saturation approach. ResultsReviewers identified 7 core themes from the focus groups. The themes identified encompassed the following: (1) challenges with securing medications and insurance concerns; (2) the experience of living with HAE before the advent of newer and more effective therapeutic options; (3) a worsening of HAE attack frequency and severity with aging; (4) the effects of comorbid conditions such as arthritis, memory loss, and irritable bowel syndrome; (5) changes in HAE with menopause; and (6) changing perspective on HAE with age, the effect of HAE on interpersonal relationships including the decision to have children, and goals for future care and research including support groups and a desire to be included in clinical trials. ConclusionOlder adults with HAE have specific challenges and concerns that may be unique compared with younger populations. Health care providers should address these to provide optimal care.

Key Findings and Experience in the Management of Juvenile Recurrent Parotitis with Sialoendoscopies—A Retrospective Study

Introduction: Juvenile recurrent parotitis (JRP) is characterized by intermittent swelling of one or both parotid glands, accompanied by pain and associated with non-obstructive sialectasia. Sialoendoscopy is considered a significant treatment for JRP, being a safe and minimally invasive treatment method with good clinical outcomes. The purpose of this study was to assess the procedure of sialoendoscopy as a treatment modality for JRP and discuss the relevant literature on this topic. Methods: This study retrospectively reviewed clinical records of children diagnosed with JRP who were treated in the Maxillofacial Department of the Tzafon Medical Center, Poriya, Israel, with sialoendoscopy between May 2016 and March 2023. Data on demographics, the site of symptoms, follow-up duration, treatment outcome, and complications were collected for each patient. The inclusion criteria were patients not older than 16 years of age, with at least two episodes of swelling of the parotid gland unilaterally or bilaterally during a time period of 6 months. The exclusion criteria were patients older than 16 years of age, and patients who were diagnosed with sialolithiasis or Sjogren’s syndrome. Results: The study included 17 children, of whom 12 (70%) were boys and 5 (30%) were girls. The mean age of the children at the time of the procedure was 6.7 years and ranged from 3 to 16. The affected parotid gland was the left in 7 children (41%), right in 9 children (53%), and bilateral in 1 child (6%). The average follow-up time was 45.17 months and ranged from 5 to 81 months. A total of 15 children (88%) were deemed to have a successful treatment result regarding the frequency of episodes after therapy and subjective improvement. Full resolution was seen in 10 children (59%). The sialoendoscopy findings were avascularity in the walls of the parotid duct, strictures, and mucous plugs. Pathological findings in sialoendoscopy were found in 11 out of 12 asymptomatic contralateral glands (p-value &gt; 0.001). Conclusions: Sialoendoscopy under general anesthesia is a worthwhile and practicable treatment method for treating JRP. Satisfactory results were seen in the vast majority of patients. It is recommended to perform bilateral sialoendoscopy also in cases of a unilateral symptomatic gland. This treatment method is effective, safe, and potentially repeatable.

Clinical efficiency of the cleaved high-molecular-weight kininogen detection in the diagnosis of hereditary angioedema

Hereditary angioedema (HAE) is an orphan genetically determined disorder with recurrent episodes of swelling in various localization. HAE is divided into two groups: HAE with C1-inhibitor deficiency and without C1-inhibitor deficiency. The main diagnostic tests are: meas urements of levels and function of C1-inhibitor, and levels of C4. These tests are not useful in all cases, for example, in HAE without C1-inhibitor deficiency. The detection of cleaved high-molecular-weight kininogen (cHK), which, even in remission, is expected to be elevated both in patients with HAE due to C1-inhibitor deficiency and in HAE with normal C1-inhibitor is a promising biomarker. The aim of this study was to determine the clinical efficiency of the cHK detection in the diagnosis of HAE. According to the results of the measurements of cHK, the patients were divided into two groups. Group №1 (100% of cHK): 27 patients, of which 19 in the study regions had variants associated with HAE, 8 didn’t have. Group №2 (not 100% of cHK): 13 patients, of which one patient had a variant associated with HAE, 12 didn’t have. The obtained data demonstrate acceptable results of using the measurement of cleaved high- molecular-weight kininogen in laboratory practice in the diagnosis of HAE.