HAE Patients Research Articles

Physician awareness and understanding of hereditary angioedema: A web‐based study in Japan

AbstractObjectivesHereditary angioedema (HAE) is a rare disease with acute attacks in the skin and mucosa throughout the body including life‐threatening laryngeal edema and abdominal attacks with severe pain. Physicians, regardless of specialty, may encounter HAE patients in their daily practice; however, low disease awareness may attribute to a considerable number of undiagnosed HAE patients in Japan. This study aims to identify issues associated with the diagnosis processes of HAE and to determine levels of HAE awareness among Japanese physicians from various specialties.MethodsA web‐based quantitative survey was conducted using a physicians panel. Physicians from the following departments were included in the survey: internal medicine, dermatology, pediatrics, emergency medicine, and gastroenterological surgery.ResultsThe proportions of physicians in dermatology, pediatrics, emergency medicine, internal medicine, and gastroenterological surgery who were able to select the C1‐INH activity test as a diagnosis test for potential HAE patients were 71.8%, 59.7%, 57.1%, 40.3%, and 25.7%, respectively. Multivariate analysis showed significant association between physicians who selected “strongly suspected” AE based on the case‐scenario and physicians who had knowledge of the essential HAE symptoms (laryngeal edema, swelling after tooth extraction, swelling of the tongue, and abdominal pain).ConclusionsThis study showed that disease awareness of HAE varied among medical specialties, suggesting the importance of educational activities in academic societies and specialist accreditation in raising HAE awareness. Proper knowledge of complement testing and HAE symptoms may help not only to diagnose patients with AE‐like symptoms as AE but also to differentially diagnose HAE from AE.

Gut microbiome alterations in hereditary angioedema

BackgroundHereditary angioedema (HAE) is a rare disease with wide intra- and interindividual clinical variation. There are no reliable indicators available in clinical practice to predict the onset and severity of HAE. Uncovering the changes in the gut microbiota in HAE patients may offer insight into a missing piece of the pathogenesis and help explain the clinical heterogeneity. ObjectiveExplore whether dysbiosis exists in patients with HAE and whether there are biomarkers to indicate the episodes. MethodsFecal samples and clinical data were collected from patients with C1-inhibitor–related HAE and their healthy family members. Patients were grouped on the basis of the most recent conditions of HAE episodes and major clinical manifestations. The gut microbiota was evaluated by sequencing the 16S ribosomal RNA gene and analyzed for diversity. ResultsMicrobial richness and diversity were significantly reduced among patients who had recent HAE attacks, especially for those presenting with abdominal symptoms (P = .003 and P = .048 compared with healthy controls and patients with no recent episodes, respectively). Decreased Firmicutes and increased Proteobacteria were found among the individuals with a recent episode, along with a marked increase of pathogenic bacteria on the basis of the predictive functional profiling. Dysbiosis was restored after regular use of danazol or tranexamic acid. A combined biomarker composed of Bifidobacterium, Lachnospira, Paraprevotella, Desulfovibrio, and Staphylococcus was proposed to detect the recent edema episodes. ConclusionWe reported alterations of the gut microbiome in patients with HAE and explored the possible role of bacteria in the etiology of edema episodes, which may provide new clues for the prediction of disease course, clinical treatment, and therapeutic evaluation.

Depression and anxiety may be cause or effect of attacks in hereditary angioedema

Introduction: The study aims to determine the depression and anxiety levels of patients with hereditary angioedema using the Beck depression inventory(BDI), Beck anxiety inventory (BAI) and to compare the results with the patients' demographic characteristics, the number of attacks, attack types, and healthy controls.Methods: 60 hereditary angioedema patients and 60 healthy controls were included in the study. The demographic characteristics of the patients, the total number of attacks/months before treatment, the number of attacks according to the localization of the attacks, and the number of attacks/month after treatment were filled in retrospectively from their hospital records. BDI and BAI were used for anxiety and depression levels.Results: Median BAI (11 vs 5; p=0.001) and BDI (11 vs 7; p=0.024) in HAE patients, the ratio of patients with moderate anxiety (21.7% vs 1.7%; p=0.001) and the ratio of patients with severe anxiety (8.3% vs. 0%; p=0.001) were compared to the control group, was high. There was no statistically significant difference between the number of attacks under treatment and the BAI and BDI scores. A positive correlation was found between the number of untreated attacks and the number of attacks under treatment and the BAI score (r=0.759; p=0.001) and BDI score (r=0.599; p=0.001).Conclusions: Due to the high prevalence of depression and anxiety in HAE patients, health care providers should be attentive of this comorbidity and refer patients to mental health specialists, when needed.Keywords: Hereditary Angioedema, Beck Depression Inventory, Beck Anxiety Inventory

The prevalence of hereditary angioedema in a Chinese cohort with decreased complement 4 levels

ObjectiveHereditary angioedema (HAE) is a rare, life-threatening autosomal dominant disorder. We aimed to investigate the prevalence of HAE in a Chinese population with a decreased Complement 4 (C4) level. MethodsAll the patients present in Tongji Hospital with C4 below lower normal range were included from January 2019 to June 2020. The individual data were extracted from the database and categorized by diagnosis. Patients suspected of HAE were further evaluated by C1 inhibitor level and function test to confirm the HAE diagnosis. ResultsA total of 8226 patients were enrolled in our study, among whom 18 had symptoms similar to HAE and received C1 inhibitor level and function tests. Two (1 male and 1 female) of the 18 patients were identified as HAE patients. This means the prevalence of HAE was 2.43/10 000 among the C4-decreased population and 10.1/10 000 in the C4-decreased population with etiology undetermined. The 2 HAE patients had experienced skin and oropharynx edema attack and received tracheotomy. The female patient had a family history. Laboratory tests showed significant decrease of C4 and C1 inhibitor levels in the 2 patients, both of whom were diagnosed as type 1 HAE. ConclusionThe prevalence of HAE is low in C4-decreased patients. In a large cohort, C4 level can serve as a practical indicator to screen the HAE patients, but further testing of C1 inhibitor activity and levels is needed to confirm the diagnosis of HAE.

Validation of diagnostic and predictive biomarkers for hereditary angioedema via plasma N-glycomics.

BackgroundHereditary angioedema (HAE) is a rare disease with heterogeneous clinical symptoms. It is vitally important to predict whether an HAE patient will develop severe symptoms in clinical practice, but there are currently no predictive biomarkers for HAE stratification. Plasma N‐glycomes are disease‐specific and have great potential for the discovery of non‐invasive biomarkers. In this study, we profiled the plasma N‐glycome of HAE patients from two independent cohorts to identify candidate biomarkers.MethodsLinkage‐specific sialylation derivatization combined with matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry detection and automated data processing was employed to analyze the plasma N‐glycome of two independent type‐1 HAE cohorts.ResultsHAE patients had abnormal glycan complexity, galactosylation, and α2,3‐ and α2,6‐linked sialylation compared to healthy controls (HC). The classification models based on dysregulated glycan traits could successfully discriminate between HAE and HC with area under the curves (AUCs) being greater than 0.9. Some of the aberrant glycans showed response to therapy. Moreover, we identified a series of glycan traits with strong associations with the occurrence of laryngeal or gastrointestinal angioedema or disease severity score. Predictive models based on these traits could be used to predict disease severity (AUC > 0.9). These results were replicated in an independent cohort.ConclusionsWe reported the full plasma N‐glycomic signature of HAE for the first time, and identified potential biomarkers. These findings may play a critical role in predicting disease severity and guide the treatment of HAE in clinical practice. Further protein‐specific and prospective studies are needed to validate our findings.

Learning Curve of Ex Vivo Liver Resection and Autotransplantation in Treating End-Stage Hepatic Alveolar Echinococcosis: A RA-CUSUM Analysis.

Background: This retrospective study aimed to evaluate the safety and learning curve of ex vivo liver resection and autotransplantation (ELRA).Methods: A total of 102 consecutive end-stage HAE patients who underwent ELRA between 2014 and 2020 in West China Hospital were enrolled. The primary endpoint was major postoperative complications (comprehensive complication index, CCI > 26). The ELRA learning curve was evaluated using risk-adjusted cumulative sum (RA-CUSUM) methods. The learning phases were determined based on RA-CUSUM analysis and tested for their association with intra- and post-operative endpoints.Results: The median surgery time was 738 (659–818) min, with a median blood loss of 2,250 (1,600–3,000) ml. The overall incidence of major morbidity was 38.24% (39/102). Risk-adjusted cumulative sum analysis demonstrated a learning curve of 53 ELRAs for major postoperative complications. The learning phase showed a significant association with the hemodynamic unstable time (HR −30.29, 95% CI −43.32, −17.25, P < 0.0001), reimplantation time (HR −13.92, 95% CI −23.17, −4.67, P = 0.004), total postoperative stay (HR −6.87, 95% CI −11.33, −2.41, P = 0.0033), and postoperative major morbidity (HR 0.25, 95% CI 0.09, 0.68, p = 0.007) when adjusted for age, disease course, liver function, and remote metastasis.Discussion: Ex vivo liver resection and autotransplantation is feasible and safe with a learning curve of 53 cases for major postoperative complications.

D005 CONSISTENTLY LOW HEREDITARY ANGIOEDEMA (HAE) ATTACK RATES OBSERVED IN US PATIENTS TREATED WITH BEROTRALSTAT

Berotralstat is an oral once-daily prophylactic treatment shown to reduce HAE attack rates. Here we report the efficacy and safety of berotralstat 150mg in 72 HAE patients in the United States (US) who completed 12 months of treatment in the open-label international APeX-S study (NCT03472040).

GC1qR Antibody Can Modulate Endothelial Cell Permeability in Angioedema.

Angioedema is characterized by swelling of the skin or mucous membranes. Overproduction of the vasodilator bradykinin (BK) is an important contributor to the disease pathology, which causes rapid increase in vascular permeability. BK formation on endothelial cells results from high molecular weight kininogen (HK) interacting with gC1qR, the receptor for the globular heads of C1q, the first component of the classical pathway of complement. Endothelial cells are sensitive to blood-flow-induced shear stress and it has been shown that shear stress can modulate gC1qR expression. This study aimed to determine the following: (1) how BK or angioedema patients' (HAE) plasma affected endothelial cell permeability and gC1qR expression under shear stress, and (2) if monoclonal antibody (mAb) 74.5.2, which recognizes the HK binding site on gC1qR, had an inhibitory effect in HK binding to endothelial cells. Human dermal microvascular endothelial cells (HDMECs) grown on Transwell inserts were exposed to shear stress in the presence of HAE patients' plasma. Endothelial cell permeability was measured using FITC-conjugated bovine serum albumin. gC1qR expression and HK binding to endothelial cell surface was measured using solid-phase ELISA. Cell morphology was quantified using immunofluorescence microscopy. The results demonstrated that BK at 1µg/mL, but not HAE patients' plasma and/or shear stress, caused significant increases in HDMEC permeability. The mAb 74.5.2 could effectively inhibit HK binding to recombinant gC1qR, and reduce HAE patients' plasma-induced HDMEC permeability change. These results suggested that monoclonal antibody to gC1qR, i.e., 74.5.2, could be potentially used as an effective therapeutic reagent to prevent angioedema.

The crux of C1-INH testing in everyday lab work

BackgroundThe determination of functional C1-INH is complex and depends on methodology, sample transport, and storage conditions. In clinical practice, we encounter individuals with pathological values which then cannot be proved true, and HAE patients in whom the values were wrongly found to be normal under non-optimum conditions. We aimed to test realistic real-life sample processing conditions for accurate C1-INH determination. MethodsWe conducted two national inter-laboratory comparisons with optimal sample preparation but different dispatch conditions. We also investigated variations of temperature and time, and their influence on C1-INH. ResultsC1-INH levels showed a significantly wider dispersion under suboptimal transport conditions than under optimal conditions (p < 0.00001). Two putatively healthy patient samples turned out to be pathological. Contrary to our expectations, we found no significant trend in a specific direction when the variables of temperature, time and sample material were combined and varied under realistic conditions. However, the range of variation in [%] functionality was markedly greater in supposedly healthy volunteers. Thus, under experimental conditions we obtained false pathological results that were not far from reality. ConclusionC1- INH determination is crucial for the diagnosis of HAE. Time, temperature, and sample handling have a significant impact on this laboratory value, sometimes leading to incorrect values, inaccurate diagnoses, and inappropriate therapies. This underlines the importance of proper handling of samples. If a patient has ambiguous C1-INH values despite optimized conditions, thus hindering a conclusive diagnosis of HAE, we recommend genetic testing.

Psychosocial burden of type 1 and 2 hereditary angioedema: a single-center Canadian cohort study

BackgroundHereditary angioedema (HAE) is a rare but serious disorder associated with a multifaceted burden of illness including a high prevalence of psychiatric symptoms and impaired health-related quality of life (HRQoL). Despite recent efforts to clarify the psychosocial implications of HAE, important gaps still remain. The aim of this study was to characterize the psychosocial burden associated with HAE types 1 and 2.MethodsType 1 or 2 HAE patients (n = 17), aged 19 years or older, completed the Depression, Anxiety, Stress Scale (DASS-21) and the DSM-5 cross cutting measures to identify psychiatric symptomatology, Angioedema Quality of Life Questionnaire (AE-QoL) and the Short-Form 36-Item Health Survey version 2 (SF-36v2) to assess disease-related and generic HRQoL respectively, and the Work Productivity and Activity Impairment Questionnaire (WPAI) to measure impact on work productivity and daily activities. Data analyses were conducted using SPSS statistical software (Version 25.0; IBM, Armonk, NY). Descriptive statistics were used to summarize continuous demographics and clinical characteristics and outcomes of interest while frequency distributions were used for categorical variables. T tests were used to compare SF-36v2 domain scores to Canadian norms and sex differences in scale scores.ResultsDepression [DASS-21 score = 6.8 ± 10.2; n = 12 (71%)] anxiety [DASS-21 score = 6.2 ± 8.2; n = 13 (76%)] and stress [DASS-21 score = 10 ± 10.2; n = 13 (76%)] were prevalent. Other psychiatric symptoms warranting inquiry included mania (n = 14, 82.4%), anger (n = 14, 82.4%), sleep disturbances (n = 13, 76.5%), somatic symptoms (n = 11, 64.7%) and impaired personality functioning (n = 9, 52.9%). Mean AE-QoL score was 39 ± 18.2. Mean SF-36v2 domain scores were significantly lower than Canadian normative data for the entire sample (p < 0.05). Impairment in work productivity was minimal; mean activity impairment was 20.6% ± 21.1% [n = 11 (64.7%)]. Female participants reported significantly greater HAE-related stress [DASS; t(15) = − 2.2, p = 0.04], greater HAE-related fears [AEQoL; t(5.6) = − 2.7, p = 0.04), and lower SF-36v2 domain scores than male patients.ConclusionsStudy findings offer specific, valuable insight into the psychosocial burden of HAE with the potential to improve clinical management of HAE. Best practices for effective management of HAE should include providing holistic care to address the psychosocial and mental health of HAE patients.

Prognostic value of plasma IL-27 on biological viability of hepatic cystic echinococcosis

ObjectivesTo investigate potential biomarkers for distinguishing biological viability of hepatic cystic echinococcosis. MethodsUsing Luminex assay we measured plasma concentrations of cytokine and chemokine in patients with active and non-active cysts (hepatic cystic echinococcosis (HCE), n = 47) and stable/progressive hepatic alveolar echinococcosis (HAE, n = 38), and in comparable infection-free volunteers (n = 48). Disease progression was staged according to the classification standard. ResultsCompared with healthy controls, enhanced elevation was found of T helper 22 type cytokine interleukin (IL)-22 and chemokines Eotaxin, interferon-γ inducible protein-10, monocyte chemoattractant protein-1, and stromal cell-derived factor-1α concentrations in HAE patients, and IL-22, growth-related oncogene α, monocyte chemoattractant protein-1, regulated on activation normal T-expressed and secreted, and stromal cell-derived factor-1α concentrations in HCE patients (P < 0.05–0.001). For HCE patients, only IL-27 concentrations in non-active HCE were significantly lower than in active HCE. In logistic regression analysis, IL-27 <20.79 pg/mL was an independent risk factor for HCE biological viability with receiver operating characteristic analysis at a 44.23 pg/mL cut-off resulting in 0.72 area under the curve. ConclusionsOur findings correlate multiple cytokine and chemokine secretion patterns in HAE and HCE patients with different disease progression stages. IL-27 could serve as a referring biomarker for distinguishing HCE biological viability and provide a preliminary foundation for clinical decision-making.

Clinical profile of hereditary angioedema from a tertiary care centre in India

IntroductionHereditary angioedema (HAE) is a clinical condition which could be fatal if not identified and managed appropriately. Knowledge of this condition is mostly confined to individual case reports and literature reviews in India. In this retrospective study we describe HAE cases which presented to a tertiary care centre in India over a period of three and half years. Materials and methodsClinical case records of forty-two HAE patients diagnosed based on clinical and laboratory features were accessed after due approval from the Ethics committee. C1 esterase inhibitor (C1 INH) and C4 levels were measured using nephelometry. All relevant data was entered into Microsoft EXCEL worksheet and analysed using simple statistical tools. ResultsAmong the 42 patients diagnosed as having HAE, 37 had low C1INH levels and were diagnosed to have type 1 HAE. The remaining 5 had normal C1 INH levels and were considered probable HAE based on family history and response to HAE specific treatment. The median age of onset of symptoms was 15 years (range 5–49) and median age at diagnosis, 27.5 years (range 5–55). The median delay in diagnosis was 10 years (range 1–27 years). Family history of HAE was observed in 52.6% and 29% reported deaths in the family with HAE like disease. Low dose androgens or tranexamic acid or both were prescribed in 64.2% of the patients. Orofacial edema was the commonest clinical presentation (76%) followed by edema of the extremities (38%), GI tract symptoms (19%) and genital involvement (11.9%). ConclusionMany cases of HAE may be going undetected in India. There is a need for clinical awareness and laboratory means to accurately identify and administer appropriate treatment.

How Angioedema Quality of Life Questionnaire Can Help Physicians in Treating C1-Inhibitor Deficiency Patients?

The Angioedema Quality of Life Questionnaire (AE-QoL) is an angioedema (AE)-specific validated questionnaire, which surveys the quality of life of diagnosed patients. The questionnaire has been used in multiple clinical trials. Our aim was to investigate how the questionnaire can assist physicians in the everyday practice of following up and managing C1-inhibitor deficiency patients. In a prospective trial conducted in our center between 2016 and 2018, 125 hereditary angioedema and 10 diagnosed with acquired angioedema completed an AE-QoL during their annual follow-up visit. Laboratory indices (i.e., complement levels) were obtained for each patient. Statistical analysis comparing clinical data with QoL parameters was performed. Results of the analysis show that AE-QoL total score and number of AE attacks per year correlated well (r = 0.47; p < 0.0001). Women reached higher AE-QoL total score values than men, over a 3-year period (p = 0.0014). The highest AE-QoL total scores were reached by the 41–60-year age group; we obtained a similar result, when analyzing the four domains. No correlation was found between the AE-QoL total score and complement parameters. Patients with a negative correlation between AE-QoL total score and number of AE attacks had a positive correlation with psychologic attributes like fatigue/mood and fears/shame domains. Patients that acquired HAE showed a significant correlation between the annual number of AE attacks and the AE-QoL total scores (r = 0.46; p < 0.0001). The study establishes the use of AE-QoL as a clinical tool for follow-up which can help in the complex assessment of both hereditary and acquired HAE patients, and help to develop better therapeutic strategies.

P163 QUALITY OF LIFE OF HEREDITARY ANGIOEDEMA (HAE) PATIENTS WITH DEPRESSION OR ANXIETY RECEIVING LANADELUMAB

The objective of this post-hoc analysis was to assess health-related quality of life (HRQoL) of HAE patients with a medical history of depression or anxiety treated with lanadelumab in the HELP open-label extension (OLE), a long-term safety and efficacy extension study of HELP.

The natural course of hereditary angioedema in a Chinese cohort

BackgroundHereditary angioedema (HAE) is a rare disease with potential life-threatening risks. To study the natural course of HAE under therapy-free conditions throughout patient life is essential for practitioners and patients to avoid possible risk factors and guide treatment.ObjectivesDescribe the natural course of HAE and explore possible risk factors, providing new clues for guiding clinical prevention and treatment.MethodsA web-based survey was conducted in 103 Chinese patients with type 1 HAE. Disease progression at different age stages was provided by each participant. The data for exploring the natural course of HAE composed of two parts: one came from the participants who had never adopted any prophylactic drug for HAE; the other was from the patients with a history of medication, but only the periods before they got confirmed diagnosis and received medications were analyzed. The demographic characteristics, lifestyles, disease severity, and family history were also collected.ResultsAmong 103 patients, 14 (13.6%) had their first HAE attack before 10 years old and 51 (49.5%) between 10 and 19. The disease worsened in 83.3% of the patients in their twenties. The proportion of patients with symptoms alleviated increased after the age of 30 years old, but the disease maintained relatively severe in most cases before 50. The participants also reported 233 members shared similar symptoms of angioedema in their family and 30 had died of laryngeal edema with the median death age of 46 years old. The disease severity was not observed to be affected significantly by gender, BMI, alcohol or smoking.ConclusionsWe summarized HAE progression patterns under therapy-free conditions, showing the natural course of HAE development along with aging. Long-term prophylaxis and symptomatic treatment are recommended for all HAE patients, especially young and middle-aged and might be adjusted depending on the disease progression.

A Germany-wide survey study on the patient journey of patients with hereditary angioedema

BackgroundHereditary angioedema (HAE) is a rare genetic disease and characterized by clinical features such as paroxysmal, recurrent angioedema of the skin, the gastrointestinal tract, and the upper airways. Swelling of the skin occurs primarily in the face, extremities and genitals. Gastrointestinal attacks are accompanied by painful abdominal cramps, vomiting and diarrhea. Due to the low prevalence and the fact that HAE patients often present with rather unspecific symptoms such as abdominal cramps, the final diagnosis is often made after a long delay. The aim of this German-wide survey was to characterize the period between occurrence of first symptoms and final diagnosis regarding self-perceived health, symptom burden and false diagnoses for patients with HAE.ResultsOverall, 81 patients with HAE were included and participated in the telephone-based survey. Of those, the majority reported their current health status as “good” (47.5%) or “very good” (13.8%), which was observed to be a clear improvement compared to the year before final diagnosis (“good” (16.3%), “very good” (11.3%)). Edema in the extremities (85.2%) and in the gastrointestinal tract (81.5%) were the most currently reported symptoms and occurred earlier than other reported symptoms (mean age at onset 18.1 and 17.8 years, respectively). Misdiagnoses were observed in 50.6% of participating HAE patients with appendicitis and allergy being the most frequently reported misdiagnoses (40.0 and 30.0% of those with misdiagnosis, respectively). Patients with misdiagnosis often received mistreatment (80.0%) with pharmaceuticals and surgical interventions as the most frequently carried out mistreatments (65.6 and 56.3% of those with mistreatment, respectively). The mean observed diagnostic delay was 18.1 years (median 15.0 years). The diagnostic delay was higher in older patients and index patients.ConclusionsThis study showed that self-perceived status of health for patients is much better once the final correct diagnosis has been made and specific treatment was available. Further challenge in the future will still be to increase awareness for HAE especially in settings which are normally approached by patients at occurrence of first symptoms to assure early referral to specialists and therefore increase the likelihood of receiving an early diagnosis.

Prophylaxis of Acute Attacks with a Novel Short-term Protocol in Hereditary Angioedema Patients Requiring Periodontal Treatment.

C1-inhibitor (C1-INH) related hereditary angioedema (C1-INH-HAE) is a rare pathological condition caused by a deficiency or a functional alteration of serum protein C1-INH. Clinical manifestations are represented by recurrent, potentially life-threatening episodes of cutaneous or mucosal oedema. The present study analysed the effectiveness of a specific short-term prophylaxis protocol for the management of C1-INH-HAE patients requiring chronic periodontitis treatment. Ten consecutive C1-INH-HAE patients with mild to moderate chronic periodontitis were treated by non-surgical periodontal therapy with a full-mouth scaling approach (FMS) in two sessions 24 h apart. All patients underwent a short-term prophylaxis protocol of acute attacks based on the association of attenuated androgen (danazol), from 5 days before the first FMS session to 2 days after the second FMS session, and C1-INH concentrate given 1 h before the first FMS session. Patients were examined for periodontal changes over a 6-month period. None of patients developed complications or oedema up to 1 week postoperatively. Compared to baseline, scaling and root planing (SRP) treatment yielded, at 6 months, a statistically significant improvement in probing depth (PD) (baseline: 5.24 mm ± 0.85 mm vs 6 months: 2.96 ± 0.31 mm), clinical attachment level (CAL) (baseline: 5.46 ± 0.81 vs 6 months: 3.89 ± 0.38 mm), full-mouth bleeding score (FMBS) (baseline: 27.6 ± 2.2% vs 6 months: 18.5 ± 2.1%) and in full-mouth plaque score (FMPS) (baseline: 28.6 ± 2.4% vs 6 months: 21.66 ± 3.3%). This study showed the clinical effectiveness of the reported prophylaxis protocol in preventing acute attacks in HAE patients requiring non-surgical periodontal treatment, with no complications up to 1 week after FMS.

Resection of retrohepatic inferior vena cava without reconstruction in ex vivo liver resection and autotransplantation: a retrospective study

BackgroundRetrohepatic inferior vena cava (RIVC) resection without reconstruction in ex vivo liver resection and autotransplantation (ERAT) for advanced alveolar echinococcosis (HAE) is unclear.MethodsThis is a retrospective study of consecutive patients referred to our hospital from 2014 to 2018. Depending on the presence of a rich collateral circulation and stable blood volume in ERAT, patients did not rebuild the RIVC. Then, patients were selected some appropriate revascularization techniques for the hepatic and renal veins. Finally, all ERAT procedures were completed, and short- and long-term outcomes were observed.ResultsFive advanced HAE patients underwent ERAT without RIVC reconstruction. One patient died of circulatory failure 1 day after surgery. Another four patients, with a median follow-up duration of 18 months (range, 10–25 months), demonstrated normal liver and kidney function, no thrombosis and no HAE recurrence.ConclusionsThrough the long-term results of ERAT, the pros and cons of not reconstructing the RIVC need to be re-examined. In cases with a rich collateral circulation, the RIVC cannot be reconstructed. However, in cases requiring the resection of multiple organs, RIVC without reconstruction was prudential.

A novel functional C1 inhibitor activity assay in dried blood spot for diagnosis of Hereditary angioedema

BackgroundHereditary angioedema (HAE) is a rare genetic disease caused by deficiency or dysfunction of C1 esterase inhibitor (C1-INH). Timely and accurate diagnosis is an ongoing challenge. Measurement of plasma C1-INH activity is currently the critical standard test. We describe a novel and highly robust point-of-care assay to quantify C1-INH activity in dried blood spot (DBS). MethodsC1-INH was extracted from 3 mm punches of DBS samples and incubated with excess amount of C1 esterase (C1s). The mixture was subsequentially incubated with C1s substrate, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitation of the enzyme reaction product. ResultsThe assay was validated within a quantification range from 100 to 1500 mU/mL. The intra-day precision and accuracy ranged from 4.0% to 11.6% and −11.1% to −2.1%, and the inter-day precision and accuracy were 8.1–13.1% and −10.3% to 0.9%, respectively. Normal C1-INH activity (n = 103) ranged from 311 to 1090 mU/mL, whereas 23 out of 24 HAE patients exhibited C1-INH activity lower than 100 mU/mL. ConclusionDBS specimen collection for measurement of functional C1-INH activity in a physician’s office is straightforward and not limited by logistic considerations and therefore, appropriate for the diagnosis of HAE in high throughput diagnostic laboratories.

Health-related quality of life and its risk factors in Chinese hereditary angioedema patients

BackgroundHereditary angioedema (HAE) is a rare but serious condition characterized by unpredictable and recurrent attacks affecting the skin and mucosa. HAE has wide-ranging impacts on the health-related quality of life (HRQoL) of patients. This study aims to assess the HRQoL of Chinese patients with HAE using the 36-item Short Form Health Survey (SF-36v2) and to explore potential risk factors for low HRQoL.MethodsA total of 104 patients (47 male and 57 female) over age 18 living in China with a known diagnosis of HAE due to C1-INH deficiency completed the SF-36v2 (generic HRQoL questionnaire). The results were compared to Chinese population norms. Subgroup analysis and logistic regression were used to interpret the data.ResultsSF-36v2 showed a significant reduction in all dimensions of HRQoL (p < 0.001) in patients with HAE compared with the general Chinese population. Female patients reported significantly lower bodily pain (BP) (p = 0.039) and physical component scores (PCSs) (p = 0.027) than male patients. Patients with mucosal edema tended to report lower role-physical (RP) limitations (p = 0.031) than patients with only skin edema. There were no differences between the mean scores of the SF-36 in relation to disease subtype, age, disease severity and long-term prophylaxis. Among female patients on long-term prophylaxis, social functioning (SF) (r = − 0.404, p = 0.010), role-emotional (RE) (r = − 0.320, p = 0.044) and mental component scores (MCSs) (r = − 0.313, p = 0.049) were negatively correlated with danazol dosage. A correlation between decreased disease control and decreased HRQoL scores was found, although the correlation was not significant in terms of RE or mental health (MH) scores. The logistic regression model revealed uncontrolled disease to be a risk factor for a low PCS (odds ratio 10.77, 95% confidence interval [CI] 1.78–65.06; p = 0.010) and laryngeal edema to be a risk factor for a low MCS (odds ratio 4.75, 95% CI 1.09–20.69; p = 0.038).ConclusionsChinese HAE patients reported significantly lower HRQoL scores than the general population. Unsatisfactory disease control is a risk factor for decreased PCSs. Laryngeal edema is a risk factor for decreased MCSs.