Hereditary angioedema due to C1 inhibitor deficiency in Belarus: epidemiology, access to diagnosis and seven novel mutations in SERPING1 gene.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease. Few states in developing countries have an adequate management of HAE, but none of them belongs to the former USSR area. This study analyses data from C1-INH-HAE patients from Belarus. METHODS: Data about clinical characteristics, genetics, access to diagnosis and treatment were collected from 2010 by the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology in Minsk. A questionnaire about attacks, prophylactic (LTP) and on-demand therapy (ODT) was administered to patients. RESULTS: We identified 64 C1-INH-HAE patients belonging to 26 families, 27 (42.2%) of which were diagnosed in the last 3 years. The estimated minimal prevalence was 1:148,000. Median age at diagnosis was 29 years, with diagnostic delay of 19 years. Thirty-eight patients answered a questionnaire about therapy. Eleven patients did not use any treatment to resolve HAE attacks. Twenty-seven patients underwent ODT: 9 with appropriate treatments, and 18 with inappropriate treatments. Nine patients used LTP with attenuated androgens and 1 with tranexamic acid. Thirty-two patients answered a questionnaire about attacks and triggers: 368 angioedema attacks were reported, with an average of 10 attacks per year. We found 24 different SERPING1 variants: 9 missenses, 6 in splice sites, 6 small deletions, 2 nonsense, 1 large deletion; 7 have not been previously described. De novo variants were found in 11 patients. CONCLUSIONS: C1-INH-HAE diagnosis and management in Belarus is improved as seen from the high number of new diagnosis in the last 3 years. Next steps will be to reduce the diagnostic delay and to promote the LTP and ODT.

The Dilemma of Falls in Older Persons: Never Forget to Investigate the Syncope.

Background and objectives: Falls represent a major cause of morbidity, hospitalizations, and mortality in older persons. The identification of risk conditions for falling is crucial. This study investigated the presence of syncope as a possible cause of falls in older persons admitted to a Sub-Acute Care Unit (SACU) with a diagnosis of accidental fall after initial management in an emergency department and acute hospitalization. Materials and methods: A retrospective monocentric study of patients aged ≥65 years, consecutively admitted to a SACU with a diagnosis of fall-related trauma. All patients underwent a complete assessment of the index event and clinical status. Patients were categorized into three groups according to the identified cause of falls: (1) transient loss of consciousness (T-LOC), (2) unexplained fall (UF), and (3) definite accidental fall (AF). Results: A total of 100 patients were evaluated. T-LOC was present in 36 patients, UF in 37, and AF in 27. Of the 36 patients with T-LOC, a probable origin was identified in most cases (n = 33, 91%), 19 subjects (53%) had orthostatic hypotension, 9 (25%) a cardiac relevant disturbance, 2 (6%) a reproduced vaso-vagal syncope, 2 (6%) severe anemia, and 1 (3%) severe hypothyroidism. The T-LOC group was older and more clinically complex than the other groups. Conclusion: In older patients who recently experienced a fall event, the prevalence of syncope is relevant. In frail and clinically complex patients with falls, the identification of the underlying cause is pivotal and can be achieved through prolonged monitoring and a comprehensive assessment of the person.

Pediatric angioedema: Essential features and preliminary results from the Hereditary Angioedema Global Registry in Italy.

Isolated angioedema, which is a localized, non-pitting, and transient swelling of the subcutaneous or submucosal tissue not associated with pruritus, urticaria, or anaphylaxis, may be classified, based on genetic pattern and mediators, respectively, as acquired or hereditary and histamine- or non-histamine-induced. The pediatric population with C1-INH-HAE (Hereditary angioedema due to C1-inhibitor deficiency) is mostly symptomatic. The frequency of symptoms in such a population compared to adults seems to be lower, but we need more prospective data to conclude on this point. The HGR (Hereditary angioedema global registry), which collects symptoms in real time, will probably provide such information. In terms of treatments, pediatric patients are significantly disadvantaged due to the few studies aimed at registering treatment for this population.

A case of highly disabling orthostatic hypotension: when an integrated cardiac rehabilitation approach makes the difference.

SUMMARY: Orthostatic hypotension (OH) is a disabling condition accompanying several diseases. It has increased morbidity and mortality, and limited chances of treatment. We report a case of a patient with stable ischemic heart disease and severe OH unresponsive to usual care. A baseline 75° head-up tilt test (HUT) was positive for symptomatic OH, i.e. pre-syncope with a systolic arterial pressure drop of 35 mmHg. On top of optimal treatment, ivabradine was started. Symptoms improved within 24 hours. At a repeated HUT, the patient could tolerate the up-right position up to 25 minutes. He was able to undergo an individualized training program with further amelioration of quality of life. Thereafter, titration of ACE inhibitors became possible. Lasting benefits were present at a 6-month follow-up. To our knowledge, this is the first reported case of successful use of ivabradine to integrate cardiac rehabilitation for management of a highly disabling OH.

Cardiovascular Autonomic Nervous System in a Patient With Hereditary Angioedema Affected by COVID-19.

Autonomic nervous system (ANS) regulation in hereditary angioedema (HAE) and coronavirus disease 2019 (COVID-19) is unknown. ANS alterations could be manifested during both the acute and post-acute phases of COVID-19. Implications of acute and chronic inflammation on ANS in HAE need to be addressed. In this case report, we monitored the systolic arterial blood pressure variability and baroreflex sensitivity in a female HAE patient both before experiencing COVID-19 symptoms and one month afterward. We also tracked the heart rate variability on the day preceding symptom onset, the day of symptom onset (SYM), the day following SYM, five days after SYM, the day of the first negative nasopharyngeal swab (i.e., 12 days after SYM), and one month after symptom onset. The results of this case report provide the characterization of vascular and cardiac autonomic profiles in an HAE patient until the resolution of an acute infection, a potential trigger for the acute HAE attack.

Cardiac autonomic profile, perceived stress and environmental comfort in healthy employees during remote and in-office work.

Remote work (REMOTE) causes an overlap between working and domestic demands. The study of the cardiac autonomic profile (CAP) by means of heart rate variability (HRV) provides information about the impact of REMOTE on workers' health. The primary aim was to determine whether CAP, self-perceived stress, environmental and workstation comfort are modified during REMOTE. The secondary aim was to explore how these indices are influenced by individual and environmental work-related factors. Fifty healthy office employees alternating REMOTE and in-office (OFFICE) working were enrolled, rated self-perceived stress, environmental and workstation comfort using a visual analogue scale and performed a 24-h electrocardiogram during REMOTE and OFFICE. Stress was lower (5.6 ± 2.2 vs. 6.4 ± 1.8), environmental comfort higher (7.7 ± 1.9 vs. 7.0 ± 1.5), and the workstation comfort poorer (6.2 ± 1.8 vs. 7.5 ± 1.2) during REMOTE. CAP was similar during REMOTE and OFFICE. CAP was influenced by some work-related factors, including the presence of offspring, absence of a dedicated workspace during REMOTE and number of working hours. All these variables determined a decreased vagal modulation. The working setting seems to impact the levels of perceived stress and comfort, but not the CAP. However, individual and environmental work-related factors reduce cardiac vagal modulation during REMOTE, potentially increasing the risk of developing cardiovascular diseases.

Physiological and Psychological Response to Acute Mental Stress in Female Patients Affected by Chronic Pulmonary Arterial Hypertension: An Explorative Controlled Pilot Trial.

Little is known about physiological and psychological responses to mental stress in stable patients affected by pulmonary arterial hypertension (PAH). The current explorative controlled pilot study was conducted to investigate whether heart rate (HR) and perceived stress would differ during standardized mental stress testing in PAH patients compared to healthy subjects. Correlation analysis between HR, perceived stress, participants' psychological status and performance on the mental stress task was also performed. The study included 13 female PAH patients (average age: 44.38 ± 10.88 years; average education: 14 ± 3.07 years; mean duration of illness: 9.15 ± 5.37 years) and 13 female controls similar in age (mean age: 47.85 ± 6.36 years) and education (15.92 ± 1.55 years). Participants performed a standardized 9 min mental stress test (computer based, adaptive math task). HR and perceived stress during the task were compared to resting baseline and correlated with psychological state and task performance. Both HR and perceived stress significantly increased during mental stress in a similar way in both groups. A significant correlation was found between HR and perceived stress. Our data show that moderate mental stress has a comparable effect on HR and perceived stress increase in stable PAH patients and control subjects.

The degree of engagement of cardiac and sympathetic arms of the baroreflex does not depend on the absolute value and sign of arterial pressure variations.

Objective.The percentages of cardiac and sympathetic baroreflex patterns detected via baroreflex sequence (SEQ) technique from spontaneous variability of heart period (HP) and systolic arterial pressure (SAP) and of muscle nerve sympathetic activity (MSNA) burst rate and diastolic arterial pressure (DAP) are utilized to assess the level of the baroreflex engagement. The cardiac baroreflex patterns can be distinguished in those featuring both HP and SAP increases (cSEQ++) and decreases (cSEQ--), while the sympathetic baroreflex patterns in those featuring a MSNA burst rate decrease and a DAP increase (sSEQ+-) and vice versa (sSEQ-+). The present study aims to assess the modifications of the involvement of the cardiac and sympathetic arms of the baroreflex with age and postural stimulus intensity.Approach.We monitored the percentages of cSEQ++ (%cSEQ++) and cSEQ-- (%cSEQ--) in 100 healthy subjects (age: 21-70 years, 54 males, 46 females), divided into five sex-balanced groups consisting of 20 subjects in each decade at rest in supine position and during active standing (STAND). We evaluated %cSEQ++, %cSEQ--, and the percentages of sSEQ+- (%sSEQ+-) and sSEQ-+ (%sSEQ-+) in 12 young healthy subjects (age 23 ± 2 years, 3 females, 9 males) undergoing incremental head-up tilt.Main results.We found that: (i) %cSEQ++ and %cSEQ-- decreased with age and increased with STAND and postural stimulus intensity; (ii) %sSEQ+- and %sSEQ-+ augmented with postural challenge magnitude; (iii) the level of cardiac and sympathetic baroreflex engagement did not depend on either the absolute value of arterial pressure or the direction of its changes.Significance.This study stresses the limited ability of the cardiac and sympathetic arms of the baroreflex in controlling absolute arterial pressure values and the equivalent ability of both positive and negative arterial pressure changes in soliciting them.

Autonomic cardiac profile in male and female healthcare professionals with and without preschoolers: differences evidenced by heart rate variability analysis.

A reduced nocturnal cardiac vagal modulation has been observed in working women with preschoolers. Whether this adaptation also occurs in men remains an open question. The aim of this study was to analyze the cardiac autonomic profile of two groups of healthcare male professionals, one with and one without preschoolers, to be compared to females. Twenty-five working men with preschoolers (M_KID, age 35.41 ± 4.01 years) and 25 without (M_NOKID, 34.48 ± 6.00 years) were compared with 25 working women with preschoolers (W_KID, 37.7 ± 5.6 years) and 25 without (W_NOKID, 35.4 ± 7.2 years). A 24-h Holter electrocardiogram was performed for time and frequency domain analysis of the beat-to-beat variations of RR interval (RR) variability, during daytime (DAY) and nighttime (NIGHT). The power of RR variability in the high frequency band (HFRR) was considered as an index of cardiac vagal modulation. RR variability indices were similar in M_KID and M_NOKID during both DAY and NIGHT. In contrast, W_KID showed a reduced nocturnal HFRR compared to W_NOKID. The comparison of working men with and without preschoolers revealed no differences in the cardiac autonomic profile, in contrast with women. This suggests that sex and/or gender may represent a crucial factor in the cardiac neural control in the parental condition.

Improvement of Sympathovagal Balance by Regular Exercise May Counteract the Ageing Process. A Study by the Analysis of QT Variability.

QT interval (QT) variability analysis provides pathophysiological and prognostic information utilized in cardiac and non-cardiac diseases, complementary to those obtained from the analysis of heart period (HP) variability. An increased QT variability has been associated to a higher risk for cardiac events and poorest prognosis. Autonomic cardiovascular adaptation to internal and external challenges, such those occurring in athletes exposed to high levels of physical stress and in ageing could also be deepen by analyzing QT variability, searching for early prognostic signatures. The aim of the study was to analyze the QT variability and cardiac control complexity in a group of middle-aged half-marathon runners at baseline (B) and at a 10-year follow-up (FU). We found that the overall QT variability decreased at FU, despite the inescapable increase in age (52.3 ± 8.0 years at FU). This change was accompanied by an increase of the HP variability complexity without changes of the QT variability complexity. Of notice, over the years, the group of athletes maintained their regular physical activity by switching to a moderate intensity rather than strenuous. In conclusion, regular and moderate exercise over the years was beneficial for this group of athletes, as reflected by the decreased overall QT variability that is known to be associated to lower cardiovascular risk. The concomitant enhanced cardiac control complexity also suggests a trend opposite to what usually occurs with ageing, resulting in a more flexible cardiac control, typical of younger people.

Renin Angiotensin System Blockers and Risk of Mortality in Hypertensive Patients Hospitalized for COVID-19: An Italian Registry.

BACKGROUND: It is uncertain whether exposure to renin-angiotensin system (RAS) modifiers affects the severity of the new coronavirus disease 2019 (COVID-19) because most of the available studies are retrospective. METHODS: We tested the prognostic value of exposure to RAS modifiers (either angiotensin-converting enzyme inhibitors [ACE-Is] or angiotensin receptor blockers [ARBs]) in a prospective study of hypertensive patients with COVID-19. We analyzed data from 566 patients (mean age 75 years, 54% males, 162 ACE-Is users, and 147 ARBs users) hospitalized in five Italian hospitals. The study used systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the primary outcome. RESULTS: Sixty-six patients died during hospitalization. Exposure to RAS modifiers was associated with a significant reduction in the risk of in-hospital mortality when compared to other BP-lowering strategies (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.32 to 0.90, p = 0.019). Exposure to ACE-Is was not significantly associated with a reduced risk of in-hospital mortality when compared with patients not treated with RAS modifiers (OR: 0.66, 95% CI: 0.36 to 1.20, p = 0.172). Conversely, ARBs users showed a 59% lower risk of death (OR: 0.41, 95% CI: 0.20 to 0.84, p = 0.016) even after allowance for several prognostic markers, including age, oxygen saturation, occurrence of severe hypotension during hospitalization, and lymphocyte count (adjusted OR: 0.37, 95% CI: 0.17 to 0.80, p = 0.012). The discontinuation of RAS modifiers during hospitalization did not exert a significant effect (p = 0.515). CONCLUSIONS: This prospective study indicates that exposure to ARBs reduces mortality in hospitalized patients with COVID-19.

Current Use of Oral Anticoagulation Therapy in Elderly Patients with Atrial Fibrillation: Results from an Italian Multicenter Prospective Study-The ISNEP Study.

Background: Atrial fibrillation (AF) is the most common heart arrhythmia, and its prevalence increases with age. Oral Anticoagulant Therapy (OAT) with non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) is essential to avoid thromboembolic events in AF. However, this treatment is associated with a high risk of bleeding and low adherence in elderly patients. Aim: The aim was to evaluate the real-world use of OAT in a population of patients aged ≥80 years in twenty-three Italian centers and to investigate the tolerance of and patient satisfaction with this therapy. Methods: The ISNEP Study is a multicenter cross-sectional study enrolling patients with AF and aged ≥80 years and treated with either NOACs or VKAs. A written questionnaire was administered to each patient to evaluate the adherence to and patient satisfaction with this therapy. Results: The study included 641 patients with a mean age of 85 (82−87) years. The use of NOACs was reported in 93.0% of cases, with the remaining 7.0% treated with VKAs. A history of stroke events was reported in five (11.1%) and one (0.2%) patients in the VKA and NOAC groups, respectively. The rate of referred ecchymosis/epistaxis was significantly higher in the VKA group compared to the NOAC group (p < 0.001). Patients receiving NOACs reported a substantial improvement in their quality of life compared to the VKA group. Conclusions: A small, but not negligible, proportion of elderly AF patients is still treated with VKAs. Patients treated with NOAC have a higher level of satisfaction with the therapy and complete adherence.

How the first years of motherhood impact the cardiac autonomic profile of female healthcare professionals: a study by heart rate variability analysis.

The conciliation between career and family is a relevant issue for working women, in particular during the first years of motherhood. Data about the state of the cardiac autonomic regulation in working women with preschoolers are lacking. Aim of this study was to compare the cardiac autonomic profile of female healthcare professionals with and without preschoolers via the analysis of the variability of the time distance between two consecutive R-wave peaks (RR) from standard 24-h Holter electrocardiogram (ECG). Fifty healthy active female healthcare professionals were enrolled: 25 with at least one preschooler (W_KID) and 25 without (W_NOKID). A standard Holter ECG was obtained during a regular working day. Segments of 5000 consecutive RRs were selected during daytime (DAY) and nighttime (NIGHT). Heart rate variability analysis was performed and the following parameters were considered for comparison between the two groups: mean (µRR), variance (σ2RR), and the absolute power in high frequency component (HF) of RR (HFRR) series. HFRR was considered as a marker of vagal cardiac modulation. Only µRR significantly increased from DAY to NIGHT in both groups (699 ± 88 vs 887 ± 140 ms in W_KID and 728 ± 90 vs 942 ± 166 ms in W_NOKID). Instead, σ2RR and HFRR increased from DAY to NIGHT only in W_NOKID (from 3334 ± 2153 to 4816 ± 4063 ms2 and from 356 ± 334 to 1397 ± 1629 ms2, respectively). W_KID showed lower σ2RR and HFRR during NIGHT, compared to W_NOKID (2336 ± 3170 vs 4816 ± 4063 ms2 and 556 ± 950 vs 1397 ± 1629 ms2, respectively). The perceived stress according to the visual analogue scale was similar in the two groups (4.7 ± 2.1 in W_KID, 5.7 ± 2.1 in W_NOKID). The presence of preschoolers lowered nocturnal cardiac vagal modulation in female healthcare professionals. This might represent an adaptation with a finalistic purpose, scilicet the facilitation of a prompt reaction in case of a child's need.

Effects of Algorithmic Music on the Cardiovascular Neural Control.

Music influences many physiological parameters, including some cardiovascular (CV) control indices. The complexity and heterogeneity of musical stimuli, the integrated response within the brain and the limited availability of quantitative methods for non-invasive assessment of the autonomic function are the main reasons for the scarcity of studies about the impact of music on CV control. This study aims to investigate the effects of listening to algorithmic music on the CV regulation of healthy subjects by means of the spectral analysis of heart period, approximated as the time distance between two consecutive R-wave peaks (RR), and systolic arterial pressure (SAP) variability. We studied 10 healthy volunteers (age 39 ± 6 years, 5 females) both while supine (REST) and during passive orthostatism (TILT). Activating and relaxing algorithmic music tracks were used to produce possible contrasting effects. At baseline, the group featured normal indices of CV sympathovagal modulation both at REST and during TILT. Compared to baseline, at REST, listening to both musical stimuli did not affect time and frequency domain markers of both SAP and RR, except for a significant increase in mean RR. A physiological TILT response was maintained while listening to both musical tracks in terms of time and frequency domain markers, compared to baseline, an increase in mean RR was again observed. In healthy subjects featuring a normal CV neural profile at baseline, algorithmic music reduced the heart rate, a potentially favorable effect. The innovative music approach of this study encourages further research, as in the presence of several diseases, such as ischemic heart disease, hypertension, and heart failure, a standardized musical stimulation could play a therapeutic role.

Analysis of Heart-Rate Variability during Angioedema Attacks in Patients with Hereditary C1-Inhibitor Deficiency.

C1-inhibitor hereditary angioedema (C1-INH-HAE) is a rare disease characterized by self-limiting edema associated with localized vasodilation due to increased levels of circulating bradykinin. C1-INH-HAE directly influences patients' everyday lives, as attacks are unpredictable in frequency, severity, and the involved anatomical site. The autonomic nervous system could be involved in remission. The cardiac autonomic profile has not yet been evaluated during the attack or prodromal phases. In this study, a multiday continuous electrocardiogram was obtained in four C1-INH-HAE patients until attack occurrence. Power spectral heart rate variability (HRV) indices were computed over the 4 h preceding the attack and during the first 4 h of the attack in three patients. Increased vagal modulation of the sinus node was detected in the prodromal phase. This finding may reflect localized vasodilation mediated by the release of bradykinin. HRV analysis may furnish early markers of an impending angioedema attack, thereby helping to identify patients at higher risk of attack recurrence. In this perspective, it could assist in the timing, titration, and optimization of prophylactic therapy, and thus improve patients' quality of life.

Lack of association between heart period variability asymmetry and respiratory sinus arrhythmia in healthy and chronic heart failure individuals.

Temporal asymmetry is a peculiar aspect of heart period (HP) variability (HPV). HPV asymmetry (HPVA) is reduced with aging and pathology, but its origin is not fully elucidated. Given the impact of respiration on HPV resulting in the respiratory sinus arrhythmia (RSA) and the asymmetric shape of the respiratory pattern, a possible link between HPVA and RSA might be expected. In this study we tested the hypothesis that HPVA is significantly associated with RSA and asymmetry of the respiratory rhythm. We studied 42 middle-aged healthy (H) subjects, and 56 chronic heart failure (CHF) patients of whom 26 assigned to the New York Heart Association (NYHA) class II (CHF-II) and 30 to NYHA class III (CHF-III). Electrocardiogram and lung volume were monitored for 8 minutes during spontaneous breathing (SB) and controlled breathing (CB) at 15 breaths/minute. The ratio of inspiratory (INSP) to expiratory (EXP) phases, namely the I/E ratio, and RSA were calculated. HPVA was estimated as the percentage of negative HP variations, traditionally measured via the Porta's index (PI). Departures of PI from 50% indicated HPVA and its significance was tested via surrogate data. We found that RSA increased during CB and I/E ratio was smaller than 1 in all groups and experimental conditions. In H subjects the PI was about 50% during SB and it increased significantly during CB. In both CHF-II and CHF-III groups the PI was about 50% during SB and remained unmodified during CB. The PI was uncorrelated with RSA and I/E ratio regardless of the experimental condition and group. Pooling together data of different experimental conditions did not affect conclusions. Therefore, we conclude that the HPVA cannot be explained by RSA and/or I/E ratio, thus representing a peculiar feature of the cardiac control that can be aroused in middle-aged H individuals via CB.

Joint effect of heart failure and coronary artery disease on the risk of death during hospitalization for COVID-19.

AIMS: heart failure (HF) and coronary artery disease (CAD) are independent predictors of death in patients with COVID-19. The adverse prognostic impact of the combination of HF and CAD in these patients is unclear. METHODS AND RESULTS: we analysed data from 954 consecutive patients hospitalized for SARS-CoV-2 in five Italian Hospitals from February 23 to May 22, 2020. The study was a systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the outcome measure. Mean duration of hospitalization was 33 days. Mortality was 11% in the total population and 7.4% in the group without evidence of HF or CAD (reference group). Mortality was 11.6% in the group with CAD and without HF (odds ratio [OR]: 1.6, p = 0.120), 15.5% in the group with HF and without CAD (OR: 2.3, p = 0.032), and 35.6% in the group with CAD and HF (OR: 6.9, p<0.0001). The risk of mortality in patients with CAD and HF combined was consistently higher than the sum of risks related to either disorder, resulting in a significant synergistic effect (p<0.0001) of the two conditions. Age-adjusted attributable proportion due to interaction was 64%. Adjusting for the simultaneous effects of age, hypotension, and lymphocyte count did not significantly lower attributable proportion which persisted statistically significant (p = 0.0360). CONCLUSION: The combination of HF and CAD exerts a marked detrimental impact on the risk of mortality in hospitalized patients with COVID-19, which is independent on other adverse prognostic markers.

San Francisco Syncope Rule, Osservatorio Epidemiologico sulla Sincope nel Lazio risk score, and clinical judgment in the assessment of short-term outcome of syncope.

OBJECTIVE: The study aimed to compare the efficacy of the Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score, San Francisco Syncope Rule, and clinical judgment in assessing the short-term prognosis of syncope. METHODS: We studied 488 patients consecutively seen for syncope at the emergency department of 2 general hospitals between January and July 2004. Sensitivity, specificity, predictive values, and likelihood ratios for short-term (within 10 days) severe outcomes were computed for each decision rule and clinical judgment. Severe outcomes comprised death, major therapeutic procedures, and early readmission to hospital. RESULTS: Clinical judgment had a sensitivity of 77%, a specificity of 69%, and would have admitted less patients (34%, P < .05 vs decision rules). The OESIL risk score was characterized by a sensitivity of 88% and a specificity of 60% (admission 43%). San Francisco Syncope Rule sensitivity was 81% and specificity was 63% (admission 40%). According to both clinical rules, no discharged patient would have died. With combined OESIL risk score and clinical judgment, the probability of adverse events was 0.7% for patients with both low risk scores, whereas that for both high risk scores was roughly 16%. CONCLUSION: Because of a relatively low sensitivity, both risk scores were partially lacking in recognizing patients with short-term high-risk syncope. However, the application of the decision rules would have identified all patients who subsequently died, and OESIL risk score and clinical judgment combined seem to improve the decision-making process concerning the identification of high-risk patients who deserve admission.

Lanadelumab Injection Treatment For The Prevention Of Hereditary Angioedema (HAE): Design, Development And Place In Therapy.

Despite the efficacy of the on-demand treatment for the control of acute attacks of Hereditary Angioedema due to C1-Inhibitor Deficiency (C1-INH-HAE), the number and severity of attacks and the impairment in the quality of life of the affected patients have led to the development of a new monoclonal antibody, lanadelumab, directly addressed to the blockage of bradykinin, the principal mediator of vasodilation during angioedema attacks. It is indicated for the prophylactic treatment, it is easy to administer, highly effective and with known limited side effects. The current review summarizes the development of the drug, its clinical background and its perspectives.

Current and emerging biologics for the treatment of hereditary angioedema.

INTRODUCTION: Hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) is a rare disease with unpredictable, self-limiting and localized swelling episodes involving the cutaneous and subcutaneous tissues. In the last decade, the spectrum of the possibilities to control the disease has considerably changed with the development of biologic therapies making necessary a careful evaluation of the differences among current and emerging treatments to properly optimize the management of patients. AREAS COVERED: This review serves to summarize the literature regarding the use of biologics for the treatment of C1-INH-HAE. Medications already available on the market and new drugs in different phases of development are addressed. EXPERT OPINION: The advent of biologic therapies dramatically improved the lives of patients with C1-INH-HAE although further improvement is still needed. Whether this is cost/effective will be answered in the next years when we will see if these major advances will benefit the majority of the patients.