Using an extended treatment regimen of lanadelumab in the prophylaxis of hereditary angioedema: a single-centre experience.

Aim: To explore and compare the efficacy of standard (300 mg every 2 weeks) and extended (300 mg every 4 weeks) dosing regimens of lanadelumab for long-term prophylaxis of hereditary angioedema (HAE). Methods: We conducted a retrospective chart review of all patients with HAE on lanadelumab, which identified a total of 9 patients: 5 females and 4 males. The median age of patients was 31 years (IQR 20.7). The mean number of attacks per month before starting lanadelumab was 5.9 (SD 6.3). Patients were started on 300 mg of lanadelumab subcutaneously, every 2 weeks (standard group, n = 5) or every 4 weeks (extended group, n = 4). Results: We observed a statistically significant improvement in the number of angioedema attacks per month in all 9 patients (p = 0.007). Five out of 9 patients (56%) achieved complete remission from attacks after starting lanadelumab. The effect of lanadelumab on number of angioedema attacks was significant in both groups; extended group (p = 0.03) and standard group (p = 0.01). Conclusion: Lanadelumab is a safe and effective agent for long-term prophylaxis of HAE. An extended dosing regimen was equally effective as prophylaxis compared to a standard regimen. Further studies are needed to compare the 2 regimens in a larger patient group.

Demographic and clinical patterns of severe asthma in the Middle East.

BACKGROUND: Severe asthma is a major burden on health-economic resources; hence, knowing the epidemiology of these patients is important in planning and provision of asthma care. In addition, identifying and managing the comorbidities helps improve symptoms and reduce associated morbidity and mortality. OBJECTIVES: Epidemiology of difficult asthma has not been well studied in the Middle East, so in this study, we present the demographic and clinical characteristics of severe asthma in the United Arab Emirates (UAE). METHODS: We retrospectively reviewed the notes of severe asthma patients attending three tertiary care hospitals between May 2015 and December 2019. Data on baseline demographics, asthma characteristics, treatment, and comorbidities were collected. RESULTS: We reviewed the notes of 458 patients (271 females and 187 males) that fulfilled the 2019 Global Initiative for Asthma guidelines for the diagnosis of severe asthma. The mean age was 47.7 (standard deviation 17.2) years. Males had significantly higher asthma control test scores (17.9 vs. 16, P = 0.01) and mean blood eosinophils (0.401 vs. 0.294, P <0.01) than females. The most common comorbidity observed was allergic rhinitis (52.2%) followed by gastroesophageal reflux disease (27.1%). In total, 109 (23.8%) patients were on biological therapies with most patients being on omalizumab and dupilumab (29 and 18 patients, respectively). Most patients were nonsmokers (97.2%), and majority were of TH2-high phenotype (75.7%). CONCLUSIONS: In this first report of severe asthma characteristics in the UAE, we found a pattern of female preponderance and most patients having a Th2-high phenotype. The findings are likely to help optimize asthma care in the region in the era of biologic therapies.

Serum Copeptin levels in the emergency department predict major clinical outcomes in adult trauma patients.

BACKGROUND: Early prognostication in trauma patients is challenging, but particularly important. We wanted to explore the ability of copeptin, the C-terminal fragment of arginine vasopressin, to identify major trauma, defined as Injury Severity Score (ISS) > 15, in a heterogeneous cohort of trauma patients and to compare its performances with lactate. We also evaluated copeptin performance in predicting other clinical outcomes: mortality, hospital admission, blood transfusion, emergency surgery, and Intensive Care Unit (ICU) admission. METHODS: This single center, pragmatic, prospective observational study was conducted at Arcispedale Santa Maria Nuova, a level II trauma center in Reggio Emilia, Italy. Copeptin determination was obtained on Emergency Department (ED) arrival, together with venous lactate. Different outcomes were measured including ISS, Revised Trauma Score (RTS), hospital and ICU admission, blood transfusion, emergency surgery, and mortality. RESULTS: One hundred and twenty five adult trauma patients admitted to the ED between June 2017 and March 2018. Copeptin showed a good ability to identify patients with ISS > 15 (AUC 0.819). Similar good performances were recorded also in predicting other outcomes. Copeptin was significantly superior to lactate in identifying patients with ISS > 15 (P 0.0015), and in predicting hospital admission (P 0.0002) and blood transfusion (P 0.016). Comparable results were observed in a subgroup of patients with RTS 7.84. CONCLUSIONS: In a heterogeneous group of trauma patients, a single copeptin determination at the time of ED admission proved to be an accurate biomarker, statistically superior to lactate for the identification of major trauma, hospital admission, and blood transfusion, while no statistical difference was observed for ICU admission and emergency surgery. These results, if confirmed, may support a role for copeptin during early management of trauma patients.

Efficacy and Safety of Biologic Agents in Chronic Urticaria, Asthma and Atopic Dermatitis - A Real-life Experience.

INTRODUCTION: Several biologic agents have been approved for the treatment of asthma, chronic urticaria and atopic dermatitis. These therapeutic agents are especially useful for patients with severe or refractory symptoms. We present the real-life experience of four of the commonly used biologic agents in the United Arab Emirates. METHODS: In this retrospective observational study, we reviewed the demographic, clinical, laboratory and treatment parameters for all patients treated with biologic agents. RESULTS: 270 patients received biologics at our centre between May 2015 and December 2019 with a median age of 36.5 years. Omalizumab was the most prescribed agent (n=183, 67.8%) followed by dupilumab (n=54, 20%), benralizumab (n=22, 8.1%) and mepolizumab (n=11, 4.1%). Urticaria was the commonest treatment indication (n=148, 55%) followed by asthma (n=105, 39%) and atopic dermatitis (n=13, 5%). All chronic urticaria patients were treated with omalizumab and showed improvement in the mean urticaria control test score from 6.7±4.47 to 12.02±4.17, with a p-value of 0.001. Dupilumab was found to be the most commonly prescribed drug for asthma (37%), followed by omalizumab (32%), benralizumab (21%) and mepolizumab (10%). The mean Asthma control test score for all asthmatics combined increased from 17.06 ± 5.4 to 19.44 ± 5.6, with p-value 0.0012 with treatment; FeNO reduced from 60.02 ± 45.74 to 29.11 ± 27.92, with p-value 0.001 and mean FEV1 improved from 2.38L ± 0.8 to 2.67L ± 0.78, with p-value 0.045. Only 4 patients in the entire cohort reported adverse events. CONCLUSION: Our study demonstrated that biological agents are a safe and effective treatment for atopic asthma, chronic urticaria and atopic dermatitis.

Improved Detection of Tuberculosis and Multidrug-Resistant Tuberculosis among Tibetan Refugees, India.

The incidence of tuberculosis (TB) among Tibetan refugees in India is 431 cases/100,000 persons, compared with 181 cases/100,000 persons overall in India in 2010. More than half of TB cases in these refugees occur among students, monks, and nuns in congregate settings. We sought to increase TB case detection rates for this population through active case finding and rapid molecular diagnostics. We screened 27,714 persons for symptoms of TB and tested 3,830 symptomatic persons by using an algorithm incorporating chest radiography, sputum smear microscopy, culture, and a rapid diagnostic test; 96 (2.5%) cases of TB were detected (prevalence 346 cases/100,000 persons). Of these cases, 5% were multidrug-resistant TB. Use of the rapid diagnostic test and active case finding enabled rapid detection of undiagnosed TB cases in congregate living settings, which would not have otherwise been identified. The burden of TB in the Tibetan exile population in India is extremely high and requires urgent attention.

Severe breathing and swallowing difficulties during routine restorative dentistry.

UNLABELLED: Although sporadically reported after dental examination, subcutaneous emphysema may be erroneously confused with an allergic, or anaphylactic, reaction. We herein report a case of a 57-year-old Caucasian woman who came to our attention after restorative treatment for a carious mandibular right second primary molar. During dental examination, an air driven hand-piece was used to restore occlusal caries. Suddenly, swallowing and breathing difficulties and a facial swelling involving the neck and, partially, the face occurred. She was urgently transported to the Emergency Department with the suspicious of allergic reaction. Clinical examination revealed palpable crepitus at the level of the head, neck and pre-sternal region but no inflammation, trismus or fluid collection was detected. A Chest X-ray first and a computed tomography scan later showed air in the deeper regions from the peri-mandibular and retro-mandibular spaces to the sub-maxillary and latero-cervical area along the vascular sulcus and retropharyngeal space descending into the mediastinal space. So, the patient was admitted for respiratory monitoring and started intravenous administration of largespectrum antibiotics and analgesics. Her hospital course was unremarkable and 5 days later she was discharged after regression of symptoms and complete radiological resolution. Three months after discharge, the patient was clinically free of recurrence. KEY WORDS: Dental care, Pneumomediastinum, Restorative dentistry.

"Freezing" parasites in pre-Himalayan region, Himachal Pradesh: Experience with mini-FLOTAC.

BACKGROUND: Helminths and protozoa infections pose a great burden especially in developing, countries, due to morbidity caused both by acute and chronic infections. Data on distribution of intestinal parasitic infections among the native and expatriates populations in Himachal Pradesh are scarce. The aim of our survey was to analyze the intestinal parasitic burden in communities from Dharamsala, Kangra district, in clinical and public health settings. We also field-tested the mini- FLOTAC, an innovative diagnostic device. METHODS: Subjects referring to the Tibetan Delek Hospital for abdominal discomfort and all children of the Tibetan Primary School in Dharamsala were screened for intestinal parasitic infections with direct smear, formol-ether concentration (FEC) method and mini-FLOTAC, their clinical history was recorded, and correlations between clinical symptoms and infections analyzed. RESULTS: 152 subjects were screened for intestinal parasites, of which 72 subjects in the outpatients department (OPD) (36 expatriates and 36 natives) and 80 in the school. 60% of schoolchildren and 57% of OPD patients were found positive for any infection, the most represented were protozoa infections (50%), whereas helminthic infections accounted only for 13% and 20% in OPD patients and schoolchildren, respectively. The most prevalent among helminths was Ascaris lumbricoides (11%). Giardia intestinalis was more present among schoolchildren than the OPD patients (20% vs 6%) and E. histolytica/dispar was more prevalent among the OPD patients (42%) than the school children (23%). Correlations were found between nausea and loose or watery stools and parasitic infections, particularly in expatriates, whereas schoolchildren, despite being as infected as adults, were completely asymptomatic. Mini-FLOTAC detected higher number of helminth infections whereas FEC method was more accurate for the diagnosis of protozoa. CONCLUSIONS: This study presents an accurate snapshot of intestinal parasitic infections in Dharamsala, and their high prevalence calls for more awareness and control measures. Mini-FLOTAC is a promising and simple technique for the diagnosis of helminth infections.

Mini-FLOTAC, an innovative direct diagnostic technique for intestinal parasitic infections: experience from the field.

BACKGROUND: Soil-transmitted helminths and intestinal protozoa infection are widespread in developing countries, yet an accurate diagnosis is rarely performed. The aim of this study was to evaluate the recently developed mini-FLOTAC method and to compare with currently more widely used techniques for the diagnosis of intestinal parasitic infections in different settings. METHODOLOGY/PRINCIPAL FINDINGS: The study was carried out in Dharamsala, Himachal Pradesh, India, and in Bukumbi, Tanzania. A total of 180 pupils from two primary schools had their stool analyzed (n = 80 in Dharamsala and n = 100 in Bukumbi) for intestinal parasitic infections with three diagnostic methods: direct fecal smear, formol-ether concentration method (FECM) and mini-FLOTAC. Overall, 72% of the pupils were positive for any intestinal parasitic infection, 24% carried dual infections and 11% three infections or more. The most frequently encountered intestinal parasites were Entamoeba coli, Entamoeba histolytica/dispar, Giardia intestinalis, hookworm, (and Schistosoma mansoni, in Tanzania). Statistically significant differences were found in the detection of parasitic infections among the three methods: mini-FLOTAC was the most sensitive method for helminth infections (90% mini-FLOTAC, 60% FECM, and 30% direct fecal smear), whereas FECM was most sensitive for intestinal protozoa infections (88% FECM, 70% direct fecal smear, and 68% mini-FLOTAC). CONCLUSION/SIGNIFICANCE: We present the first experiences with the mini-FLOTAC for the diagnosis of intestinal helminths and protozoa. Our results suggest that it is a valid, sensitive and potentially low-cost alternative technique that could be used in resource-limited settings--particularly for helminth diagnosis.

Pentraxin-3 as a marker of disease activity in Takayasu arteritis.

BACKGROUND: Because pentraxin-3 (PTX3) is produced by immune and vascular cells in response to proinflammatory signals, it may be a useful biomarker for defining disease activity in patients with Takayasu arteritis. OBJECTIVE: To compare PTX3 levels in patients who have Takayasu arteritis with those in healthy and infected controls, and to compare accuracy of PTX3 levels with that of C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) for distinguishing active and inactive disease. DESIGN: Cross-sectional, noninterventional study conducted between September 2005 and October 2008. SETTING: Immunology and rheumatology clinic at a university hospital in Italy. PATIENTS: 57 consecutive patients with Takayasu arteritis and known disease activity, 57 healthy blood donor controls, and 15 patients with acute infection. MEASUREMENTS: Disease activity by clinical criteria; plasma PTX3 and CRP levels and ESR. RESULTS: 27 patients had active Takayasu arteritis; 30 had inactive disease. Levels of PTX3 were higher in patients with active disease (median, >2.14 ng/mL [range, 0.57 to 48.18 ng/mL]) than in those with inactive disease (median, 0.63 ng/mL [range, 0.00 to 1.64 ng/mL]) and were higher than in healthy patients (median, 0.11 ng/mL [range, 0 to 1.20 ng/mL]) or those with acute infection (median, 0.26 ng/mL [range, 0 to 0.75 ng/mL]). A plasma PTX3 level greater than 1 ng/mL was more accurate than normal thresholds of CRP or ESR for distinguishing active from inactive disease. LIMITATION: The study excluded patients with unknown or equivocal disease status. CONCLUSION: Plasma levels of PTX3 could help distinguish active from inactive Takayasu arteritis but should not be adopted for clinical use until the findings are confirmed in a broader spectrum of patients whose disease activity is unknown or equivocal before testing.

Efficacy of traditional and biologic agents in different clinical phenotypes of adult-onset Still's disease.

OBJECTIVE: To evaluate the efficacy of antiinflammatory agents, steroids, immunosuppressants, and biologic agents in patients with adult-onset Still's disease (AOSD) who have either chronic articular disease or nonchronic disease. METHODS: Forty-five patients with AOSD were seen and followed up for at least 2 years at our institution, from 1991 to 2008. The majority of patients were treated with several therapeutic regimens; a total of 152 efficacy trials were administered. Data regarding the type of medication, the dosage used, and the outcome of these trials were collected and analyzed. RESULTS: Our data showed that the efficacy of monotherapy with a nonsteroidal antiinflammatory drug was very low (16%) and confirmed good efficacy of steroid therapy (63%), particularly in patients without chronic articular disease (78%). Patients whose disease did not respond to steroid therapy at the time of disease onset were at risk of the subsequent development of chronic arthritis. Disease-modifying antirheumatic drug (DMARD) monotherapy was successful in controlling steroid-resistant or steroid-dependent disease in 60% of patients. Methotrexate and cyclosporine showed the best response rates. The combination of high-dose steroids and cyclosporine was administered to successfully control some acute life-threatening complications. Only 6 patients had disease that was both steroid resistant and DMARD resistant. Treatment with biologic agents eventually led to satisfactory control of disease manifestations in 5 (83%) of these 6 patients. CONCLUSION: Steroids were less effective in patients with chronic articular disease than in those with nonchronic disease. The administration of DMARDs early after disease onset could be beneficial in patients with steroid-resistant disease who are at risk of the development of chronic articular disease. Biologic agents proved to be highly effective in both steroid-resistant and DMARD-resistant AOSD.