Real Clinical Practice Research Articles

Efficacy and safety of regorafenib for the treatment of metastatic colorectal cancer in routine clinical practice: results from a Spanish hospital

IntroductionRegorafenib is indicated as treatment in third-line and beyond in patients with metastatic colorectal cancer.Methods This is a retrospective study of a cohort of patients with mCRC treated with regorafenib in Hospital Universitario Ramón y Cajal, in Madrid, Spain.ResultsWith the aim to assess the efficacy and safety of regorafenib, 91 patients treated between 2013 and 2023 were included. Only 1.1% of patients achieved disease control. Median progression free survival was 2.40 months and median overall survival was 4.76 months. The most frequent adverse events were fatigue and hand-foot skin reaction (59.34% and 28.57%, respectively).DiscussionOur results confirm the safety of regorafenib as treatment of mCRC in real clinical practice. Although our population is less pretreated than in the CORRECT trial, our disease control rate was inferior. This difference may be due to a worse baseline status and a high percentage of hepatic disease showed in our patients.

Tolerability of perioperative chemotherapy for gastric cancer in real clinical practice

Background. The choice of the optimal scheme of perioperative chemotherapy of locally advanced gastric cancer is an urgent problem in real clinical practice. Aim. To analyze therapy tolerability in this cohort of patients. Materials and methods. Perioperative chemotherapy of gastric cancer was performed in 90 patients in the Chemotherapy Department of the Oncology Center №1 of the Yudin City Clinical Hospital from January 2021 to February 2024. Results. The incidence of severe complications at the preoperative stage was 41.9% for the FOLFOX regimen and 40.7% for the FLOT regimen, at the adjuvant stage – 17.4 and 43.2%, respectively. Operative treatment was successfully performed in 79 (87.8%) patients, and the full scope of combined treatment of locally advanced gastric cancer was completed in 59 (65%) patients. 80.8% of pathomorphologic responses in the FOLFOX group and 67.9% in the FLOT group were TRG3-4, with complete response noted in only one patient. Conclusion. High toxicity rates in elderly and comorbid patients on the FOLFOX regimen require the development of an individualized approach to the treatment of this group of patients.

Retrospective analysis of the safety and efficacy of Pembroria® during non-medical switching from the original drug Keytruda® in patients with advanced malignancies of various localizations in real clinical practice

Introduction. The emergence of genetically engineered biological drugs is rightly considered a revolutionary event in medicine. In 2022, the first biosimilar of pembrolizumab, the Russian drug Pembroria®, was approved. One of the study types that can convincingly demonstrate the safety and efficacy of biosimilar is its use for switching from the original drug for non-medical indications (NMS, or non-medical switching) according to standard approaches of real clinical practice and the drug label. Aim. To assess the safety of NMS switching in patients with advanced malignancies of various localizations from the original drug Keytruda® to the biosimilar Pembroria® and to evaluate its effectiveness in real clinical practice. Materials and methods. We analyzed the data of 114 patients with advanced malignancies of various localizations and the last line of treatment with Keytruda® as monotherapy or in combination with other agents within the approved indications and switched to Pembroria® for NMS. After switching to Pemboria®, patients did not change treatment for another checkpoint inhibitor within this line of therapy. Results. The incidence of immune-mediated adverse reactions (imARs) of any severity during treatment with comparators differed slightly: 57% with Keytruda® and 54% with Pembroria®. The majority of imARs with both Keytruda® and Pembroria® were Grade 1 in severity (69% and 86%, respectively). All serious ARs were resolved and did not result in drug discontinuation. When analyzing the best objective response to treatment with Keytruda®, complete response, partial response, and stabilization were observed in 9 (7.9%), 28 (24.6%), and 61 (53.5%) cases, respectively, during treatment with Pemboria® – in 8 (7%), 24 (21%), 52 (45.6%) cases, respectively. Conclusion. The safety profile of Keytruda® and Pembroria® is acceptable and comparable: the imAR rate with Pembroria® when switching from Keytrada® did not exceed that with the original drug Keytruda®; in most patients, switching from Keytruda® to Pembroria® was not associated with an increase in the imAR rate or severity. The majority of patients maintained disease control when switched to Pembroria®.

The combination of lenvatinib and pembrolizumab in the treatment of patients with metastatic kidney cancer and factors of poor prognosis: experience of clinics in Moscow: A prospective observational study

Background. Combination therapy is the standard of care for intermediate and poor prognosis metastatic renal cell carcinoma. In the IMDC prognostic classification, tumor stage and histological type are not considered due to the lack of independent impact on overall survival. The CLEAR study demonstrated the efficacy of lenvatinib and pembrolizumab combination in long-term treatment outcomes, including overall survival in poor prognosis compared to sunitinib. The KEYNOTE-B61 study demonstrated high efficacy of this combination in patients with non-clear cell renal cell carcinoma. Aim. To evaluate the efficacy of the combination of lenvatinib and pembrolizumab in patients with high tumor burden and non-clear cell histotypes. Materials and methods. This prospective observational study included 54 patients with metastatic renal cell carcinoma who received a combination of lenvatinib and pemrolizumab in the first line between 2022 and May 2024 in oncology clinics of the Moscow Department of Health. Clear cell histotype was represented in 79.6% of cases, 14.8% had papillary cancer, and 5.6% of patients had chromophobe cancer. The primary endpoint was the objective response rate. Results. The objective response was assessed in 50 patients. The objective response rate was 38%, including 2% complete response according to RECIST 1.1, disease progression was in 8% of patients. The median depth of response was -25% (from -100% to +28). The median time to response was 12.4 weeks (1.1–38.3). Conclusion. The efficacy of the combination of lenvatinib and pembrolizumab in real-life clinical practice outside the inclusion criteria of the CLEAR study is clinically significant and allows us to expect improvement even in patients with a large volume of metastatic process and non-clear cell histotype, but the expected benefit in patients with unsatisfactory somatic status remains disputed.

Enhancing Clinical Education Training with Immersive Reality (XR)

A core element of clinical education is the observed structured clinical examination (OSCE) that simulates real-life clinical practice. These OSCEs can be enhanced through combining the best elements of emerging technologies in the design of enhanced simulation environments to prepare healthcare graduates for changing clinical practice as it integrates new and emerging technologies. New and emerging immersive reality (XR) headsets that allow digital enhancement of practice with real tools and procedures can be combined with haptic feedback such as a high-fidelity manikin within an interactive immersive room that can replicate a wide variety of real-world scenarios at the touch of a button. In this way XR can enhance authentic learning in clinical and first responder practice by enabling exposure to critical elements of clinical simulation in a safe, contextual learning environment that is cost effective and scalable compared to the expense of simulations involving actors and physical real-life sets. In response this concise paper introduces the development of a framework for enhanced simulation practice using the Blended Learning Simulation Suite (BLISS).

Comparative analysis of the efficacy and safety of non-immunogenic staphylokinase and alteplase in bridging therapy of ischemic stroke

Introduction. Bridging therapy is the main method of treating ischemic stroke (IS) due to proximal occlusion, the effectiveness of which depends on the speed of its implementation. It is possible to increase the speed of systemic thrombolytic therapy (STT) and reduce the delay before mechanical thrombectomy (MT) by using bolus forms of thrombolytic drugs.Aim. To evaluate the efficacy and safety of using non-immunogenic staphylokinase compared to alteplase in bridging therapy of IS in real clinical practice of a regional stroke center (RSC).Materials and methods. A retrospective study of the combined use of STT and MT for the treatment of IS due to proximal occlusion was conducted from the reperfusion therapy registry of the RSC of the Tomsk Regional Clinical Hospital from 2017 to 2023. The final analysis included 49 patients who received non-immunogenic staphylokinase and 26 patients who received alteplase.Results. The time between the stages of bridging therapy was 92.0 [65.0–130.0] min in the non-immunogenic staphylokinase group and 35.0 [25.0–50.0] min in the alteplase group (p < 0.001). No intergroup differences were found in the incidence of symptomatic hemorrhagic transformation: 8.1% in the non-immunogenic staphylokinase group and 3.8% in the alteplase group (p = 0.476). Mortality in both groups did not differ significantly and was 30.6% and 26.9%, respectively. Favorable functional outcome was observed in 40.8% of patients in the non-immunogenic staphylokinase group and in 23.1% in the alteplase group (p = 0.151).Conclusion. Comparable efficacy and safety of non-immunogenic staphylokinase and alteplase in the context of staged reperfusion therapy were revealed. The use of non-immunogenic staphylokinase is associated with a decrease in the time between the stages of bridging therapy.

Four-month real-life response to Tezepelumab in patients with multi-failure to other biologics.

To evaluate the response to Tezepelumab in real clinical practice, we performed an analysis of the clinical, functional, and inflammatory characteristics of 13 patients with severe asthma after completing four doses of Tezepelumab was performed. When comparing clinical parameters such as asthma control test (ACT), FENO value, exacerbations in the last 4 months, blood eosinophils and FEV1%, before receiving Tezepelumab and after four doses of Tezepelumab, statistically significant differences were found in ACT levels (p=0.0072), exacerbations (p=0.018) and FEV1% (p=0.012) before and after four doses of Tezepelumab. No statistically significant differences were found in blood eosinophils or FeNO levels, however, a mean reduction of 102.5±231 cells/mm3 and 14.67±30 ppb, respectively, was observed. Patients with a high T2 profile had significantly higher baseline FeNO (p<0.05), but no significant improvement in lung function or asthma control was observed in this group. Patients with Aspirin-exacerbated respiratory disease (AERD) were evaluated separately. There was no difference in ACT, FeNO, or lung function changes after tezepelumab use compared to patients without AERD (all p>0.05). We demonstrated, in a multicenter study, the clinical improvement associated with tezepelumab treatment in severe uncontrolled asthma, independent of inflammatory biomarkers, eosinophilic profile, or previous biological failure.

Effect of metformin therapy on the development of vitamin B12 deficiency in patients with type 2 diabetes mellitus

Introduction. For the past decades, metformin has been the drug of choice for the treatment of patients with type 2 diabetes mellitus (T2DM). However, its long-term use leads to a number of side effects, such as the development of vitamin B12 deficiency (VB12).Aim. Assess the safety of metformin use in real clinical practice in the treatment of patients with type 2 diabetes based on the analysis of the incidence of VB12 deficiency.Materials and methods. Sixty patients with T2DM aged 27 to 65 years were examined in a city polyclinic. The average anamnestic duration of T2DM was 68 [4; 291] months. All patients were on selected hypoglycemic therapy: 19 patients (31.7%) received metformin monotherapy, and 41 patients (68.3%) received metformin as part of combination therapy. The average duration of metformin therapy was 62 [3; 291] months. All patients underwent analysis of the VB12 content in the blood serum depending on the duration of metformin intake. Results. The average VB12 level in the examined patients was 345 [99; 770] pg/ml. Normal VB12 levels were observed in 51 (85%) patients (386 [221; 770] pg/ml), VB12 deficiency (&lt;200 pg/ml) was detected in 9 (15%) patients (146 [99; 195] pg/ml), the differences between VB12 levels were significant (p &lt; 0.05). At the same time, in 37 (61.7%) patients with normal VB12 levels, its values were assessed as borderline (in the range of 200–450 pg/ml), and amounted to 335 [221; 470] pg/ml. VB12 deficiency developed more often in patients taking metformin for more than 1 year (16.7%), borderline VB12 levels were more often found in patients taking metformin for less than a year (58.3%) and more than 5 years (71%). However, the dependence of VB12 levels on the duration of metformin intake was not significant (p &gt; 0.05).Conclusion. Metformin use results in the development of VB12 deficiency in every sixth patient with T2DM, primarily after one year of treatment.

Observational, cross-sectional study to describe the efficacy and safety of intranasal Esketamine treatment in real clinical practice: INtegrate study

Observational, cross-sectional study to describe the efficacy and safety of intranasal Esketamine treatment in real clinical practice: INtegrate study

Glucosuria as a major mechanism-associated effect of sodium-glucose cotransporter 2 inhibitors: Is there cause for concern?

Introduction. One of the main mechanisms of action of SGLT2 inhibitors is an increase in renal excretion of glucose and sodium, development of glucosuria against the background of decreased levels of daily glycemia. The frequency of glucosuria development in patients without DM/prediabetes, receiving SGLT2 inhibitors for the treatment of CHD or CKD, as a consequence of the mechanism of action of SGLT2 inhibitors inhibitors is poorly studied and seems to be very interesting.Aim. To evaluate in real clinical practice the frequency of the development and severity of glucosuria in patients with CHF treated with inhibitors of SGLT2 inhibitors both on the background of concomitant DM2 and without type 2 DM.Materials and methods. Within the framework of a one-stage, prospective, observational study we evaluated the frequency of development and severity of glucosuria in patients with CHF, receiving SGLT2 inhibitors inhibitors, who were in the cardiology department of V.P. Demikhov State Clinical Hospital of Moscow. A total of 230 patients were included in the analysis.Results. The mean age of the patients was 74 [66; 83] years. Median LVEF was 36 [29; 44] %, NTproBNP 1019 [423; 2355] pg/ml. Heart failure with reduced ejection fraction (HFrEF) was recorded in 64.81% of patients, 17.13% had HF with mildly reduced ejection fraction and 18.06% had a СHF preserved ejection fraction. DM2 was present in 38.7 percent of patients with СHF. Among patients with CHF, the ‘glucosuria phenomenon’ due to the administration of SGLT2 inhibitors was observed in 31.16% of those without DM2, and in 52.27% of СHF patients with concomitant DM2.Conclusion. In patients with CHF receiving SGLT2 inhibitors therapy, the ‘glucosuria phenomenon’ developed in one in three patients without overt carbohydrate metabolism abnormalities and one in two with DM2. The findings suggest that the glucosuria effect of SGLT2 inhibitors is not a required event even in patients with DM2, which may influence the incidence of adverse events in general clinical practice. And the cardioprotective benefits of SGLT2 inhibitors may be due to other mechanisms unrelated to glucose excretion, which, according to recent studies, is considered a surrogate predictor of favorable prognosis concerning CHF and renal outcomes. Nevertheless, additional clinical and experimental studies are required to determine the cardioprotective mechanisms of SGLT2 inhibitors and the predictive value of drug-induced glucosuria.

Gastric neoplasm detection of computer-aided detection-assisted esophagogastroduodenoscopy changes with implement scenarios: a real-world study.

The implementation of computer-aided detection (CAD) devices in esophagogastroduodenoscopy (EGD) could autonomously identify gastric precancerous lesions and neoplasms and reduce the miss rate of gastric neoplasms in prospective trials. However, there is still insufficient evidence of their use in real-life clinical practice. A real-world, two-center study was conducted at Wenzhou Central Hospital (WCH) and Renmin Hospital of Wuhan University (RHWU). High biopsy rate and low biopsy rate strategies were adopted, and CAD devices were applied in 2019 and 2021 at WCH and RHWU, respectively. We compared differences in gastric precancerous and neoplasm detection of EGD before and after the use of CAD devices in the first half of the year. A total of 33 885 patients were included and 32 886 patients were ultimately analyzed. In WCH of which biopsy rate >95%, with the implementation of CAD, more the number of early gastric cancer divided by all gastric neoplasm (EGC/GN) (0.35% vs 0.59%, P=0.028, OR [95% CI]=1.65 [1.0-2.60]) was found, while gastric neoplasm detection rate (1.39% vs 1.36%, P=0.897, OR [95% CI]=0.98 [0.76-1.26]) remained stable. In RHWU of which biopsy rate <20%, the gastric neoplasm detection rate (1.78% vs 3.23%, P<0.001, OR [95% CI]=1.84 [1.33-2.54]) nearly doubled after the implementation of CAD, while there was no significant change in the EGC/GN. The application of CAD devices devoted to distinct increases in gastric neoplasm detection according to different biopsy strategies, which implied that CAD devices demonstrated assistance on gastric neoplasm detection while varied effectiveness according to different implementation scenarios.

Phosphodiesterase inhibitors and testicular torsion: A systematic review and meta-analysis of animal studies.

Testicular torsion is a common urological emergency in children and teenagers that, in most cases, requires surgical exploration and detorsion. However, even after a successful intervention, a high number of patients still develop irreversible damage. To investigate whether the administration of phosphodiesterase inhibitors (PDE) in animal models of testicular torsion can reduce damages caused by the ischemia-reperfusion syndrome. A systematic search of the Medline, Web of Science, Embase, and Ovid databases for studies up to December 2023 was performed using PRISMA guidelines. A detailed search was conducted using the following key terms: "testicles," "ischemia," "reperfusion," and "phosphodiesterase inhibitors." There was no restriction regarding language or year of publication. We investigated spermatogenesis by the Johnsen's biopsy score (JTBS) and histological damage by the Cosentino's biopsy score (CBS). Malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidase (GPx) testicular levels were also analyzed. Initially, 296 articles were identified. However, only 20 studies met the inclusion criteria. PDE inhibitors improved JTBS (MD=2.53, CI=1.94 to 3.13), CBS (MD=-1.11, CI=-1.25 to -0.97) and SOD (SMD=3.27, CI=1.59 to 4.95) outcomes. PDE did not improve MDA (SMD=-0.93, CI=-2.19 to 0.34), NO (SMD=-0.54, CI=-1.56 to 0.48), and GPx (SMD=0.77, CI=-0.38 to 1.92) outcomes. A higher dose of PDE inhibitors only improved CBS outcome. This review indicates that the administration of PDE inhibitors in rats ameliorated the outcomes, representing a promising complementary strategy for spermatogenesis recovery following testicular torsion. Our review suggests that JTBS and CBS could be translated into future human studies, validating and extending these findings within the context of human physiopathology, while providing applicability of interventions in real clinical practice.

Empaglifozin modifies the arterial stiffness in type-2 diabetic patients: a preliminary report.

Abstract Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated beneficial effects on cardiovascular and renal events in patients with type 2 diabetes mellitus. The mechanisms underlying these effects are not fully elucidated. Aim of this study was to investigate whether empagliflozin is able to modify the arterial stiffness in type 2 diabetic patients. Methods Pulse wave velocity (PWV) and other parameters of arterial stiffness were assessed before and after adding empagliflozin to a traditional antidiabetic treatment in 16 consecutive T2DM outpatients folowed for 3 months. Arterial stiffness were evaluted using SphygmoCor ECEL measuring the pulse waveform of the arterial pulse moving from tha descending aorta to the femoral artery (PWV). Data obtained from the diabetic population has been compared to 16 T2DM outpatients not treated with SGLT2 inhibitors. Results In the two groups differences according gender distribution or duration of diabetes mellitus did not emerge. However the empagliflozin group was younger compared to controls (64.1±8.68 vs 74.45±8.13, P &amp;lt; 0.05). Empagliflozin treatment significantly decreased HbA1c after 12 weeks of treatment (7.9±0.78 vs 7.04±1.09%, P &amp;lt; 0.008.). After 12 weeks’ treatment, empagliflozin significantly improved PWV compared to controls not treated with SGLT2-i (ΔPWVV -0.68±1.1 vs 0.89±1,6 p &amp;lt;0.004, P = 0.0065 with age and HbA1c as covariates). Moreover body weight significantly decreased in the empagliflozin group (86.75±16.16 vs 81.71±16.5 kg, p =0.001) compared to controls (in whom remained unchanged) as long as BMI (30.48±5.4 versus 28.75±5.66 kg/m2, P &amp;lt; 0.002) compared to controls (in whom remained unchanged). Estimated glomerular filtration rate (eGFR) remained unchanged in the two groups during the study whereas urine Albumin to Creatinine ratio significantly improved using empagliflozin (17.8±46.8 vs 12.2±35.7 mg/mmol, P = 0.049). Conclusion In this ‘real clinical practice’ experience, the potential effect of empagliflozin treatment on arterial stiffness in T2DM patients was extensively investigated. Arterial stiffness was significantly decreased adding empaglifozin to the traditional treatment and this result has been obtained after 3-month. Significantly improvement in urine Albumin to Creatinine ratio might suggest an amelioration of endothelial function in those patients that could be involved in reducing arterial stiffness.

Adherence to anti-hypertensive therapy with perindopril-based single-pill versus free-pill combinations: a 10-year real-world analysis in Italy

Abstract Background/Introduction Despite the growing availability of blood pressure-lowering drugs, hypertension remains poorly controlled and a significant mortality cause worldwide. The silent course of the disease, suboptimal adherence, and complexity of therapeutic schedules are important factors in reducing the effectiveness of anti-hypertensive treatments at the population level. With the purpose of simplifying patients’ medication self-management, guidelines have strongly endorsed the use of anti-hypertensive therapy with single-pill combinations (SPCs). Perindopril (PER)-based SPCs, including both two- and three-drug combinations, have been available since 2008. Purpose We explored treatment adherence over 10 years in patients receiving PER-based regimens (SPC or free-pill combination) in Italy. Methods A retrospective real-world analysis was conducted on administrative databases covering 6.7 million Italian health-assisted residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, those with PER-based prescriptions were identified, considering combinations with amlodipine (AML) and/or indapamide (IND), either as SPC or free-pill or mixed (SPC+separate pill). The index-date (ID) was that of the first prescription of a PER-based regimen throughout the inclusion period. All patients with at least 12 months of available data before and after the ID were included. A cross-sectional analysis evaluated the yearly adherence for the period 2012-2021, calculating the proportion of days covered (PDC) by drug prescriptions on 1-year follow-up (PDC≥80% indicated high-adherence). Results Over 2012-2021, of 121,397 patients on a PER-based therapy, those treated with SPC ranged from 87% (during 2012) to 94.4% (during 2021), while free-pill and SPC+separate pill cohorts represented, respectively, 10.6-3.5% and 2.4-2.1% of all hypertensive patients. Over the decade, the proportion of adherent patients in SPC users was markedly higher than in free-pill and SPC+separate pill cohorts (Fig. 1). The sudden reduction of adherent patients during 2018-2019 was possibly due to a temporary shortage of PER/AML/IND as SPC in Italy from Nov-2018 to Mar-2019. Multivariate analysis showed that over 2012-2021 decade, free-pill and SPC+separate pill regimens resulted in significantly lower adherence (more than 80% reduction) than SPC formulation, while male gender and older age were predictive of better adherence (Table 1). Conclusions These findings from real clinical practice in Italy highlighted a growing attitude from clinicians to prescribe more manageable anti-hypertensive schemes based on SPC formulations, in line with current guidelines. The higher proportion of adherent patients among the users of PER-based SPCs corroborates the importance of alleviating pill burden, that is a key component in blood pressure control, and so in the reduction of hypertensive complications and cardiovascular risk.

Real-world analysis exploring the association between anti-hypertensive therapy with perindopril-based single-pill combinations (SPC) and cardiovascular outcomes and all-cause mortality in Italy

Abstract Background/Introduction A combination of blood pressure (BP)-lowering medications is recommended by guidelines as an effective strategy to obtain rapid and optimal BP control in hypertensive patients. However, the prescription of multiple BP-lowering medications increases the pill burden, potentially reducing medication adherence. Guidelines also recommend using single pill combinations(SPCs) containing ≥2 anti-hypertensive medications as a practical approach to simplify treatment schedules and possibly improve adherence. Yet, real-world evidence on the association between SPC or free combination of BP-lowering medications and hyperthensive patient outcome remains limited. Purpose We compared the association of SPC versus free-pill combination(free) on cardiovascular outcomes and all-cause mortality in hypertensive patients treated with perindopril(PER)-based therapies in real clinical practice in Italy. Methods A retrospective analysis was conducted using administrative databases covering 6.7 million health-assisted Italian residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, the study included patients prescribed with a combination of PER with amlodipine(AML) and/or indapamide(IND), either as SPC or free or mixed (SPC plus separate pill) combinations. Results The analysis included 24,476 hypertensive subjects receiving a PER-based therapy, 22,663 (93%) of them using SPC, 1458 (6%) free and 355 (1.4%) mixed. The last cohort was not included in the analysis due to the small sample size (N=355). The patients in the free cohort were significantly older than those in the SPC cohort (69.5±12.3 vs. 64.3±12.2 years, p&amp;lt;0.001), showed a higher number of pre-existing comorbidities (0.5±0.8 vs. 0.4±0.7, p&amp;lt;0.001), and received a larger number of different medications (pill burden: 1.2±1.7 vs. 0.7±1.3, p&amp;lt;0.001). To minimize selection bias, the groups were balanced with propensity score and inverse probability weighting (IPW), adjusting for baseline covariates, including comorbidity profile and pill burden. The IPW-adjusted Kaplan-Meier plots and Cox’s proportional hazard model (Table 1) revealed that, compared with SPC users, patients on free regimens had a significantly increased risk of all-cause mortality (36%, p&amp;lt;0.001), all cardiovascular events (45%, p&amp;lt;0.001), ischemic heart disease (29%, p&amp;lt;0.05), cerebrovascular events (84%, p&amp;lt;0.001), and occurrence of the composite outcome cardiovascular events/all-cause mortality (40%, p&amp;lt;0.001). Conclusions This real-world data from a large Italian administrative dataset suggested that PER-based anti-hypertensive therapy with SPC results in significant clinical benefits in terms of lowered risk of cardiovascular/cerebrovascular events and all-cause mortality. Reducing pill burden and simplifying therapeutic schedules is of crucial importance to maximize the potential benefits derived from the prescription of anti-hypertensive treatment.

A higher adherence to perindopril-based anti-hypertensive therapy is associated with a reduced risk of cardiovascular outcomes and all-cause mortality in real clinical practice in Italy

Abstract Background Therapeutic management of hypertension is a landmark of cardiovascular (CV) risk prevention. Combined therapies with at least 2 anti-hypertensive agents are required in many patients in whom monotherapy and lifestyle interventions failed in blood pressure control. It is well-known that poor medication adherence remains a major barrier to achieving the therapeutic targets for all CV drugs, including anti-hypertensives. Purpose We evaluated the relationship between adherence to perindopril (PER)-based therapeutic regimen prescribed as single-pill combination (SPC) or free-pill and CV outcomes and all-cause mortality in a large Italian population. Methods A retrospective analysis was performed using administrative databases corresponding to around 6.7 million health-assisted residents. Hypertensive adults were first identified through hospitalization discharge diagnosis or exemption codes for hypertension between 2010 and 2021. Patients prescribed PER-based therapies were screened for all combinations of PER with amlodipine (AML) and/or indapamide (IND) (all formulations, single-pill or free-pill). Time of the first prescription of a PER-based regimen during the inclusion period was considered the index-date. The analysis included all hypertensive subjects prescribed a PER-based therapy, having available data at least 12 months before and 24 months after the index-date, respectively. Since the analysis was focused on the possible associations between adherence level and CV outcomes and all-cause mortality, adherence was assessed during the first year of follow-up on alive patients and outcomes were assessed during the second year. Adherence was assessed using the proportion of days covered (PDC) approach on 1-year follow-up, and considering a PDC&amp;lt;80% as poor-to-moderate adherence, and PDC ≥80% as good adherence. The Cox’s proportional hazard model was applied to estimate Hazard Ratio (HR) adjusting for baseline covariates, including comorbidity profile and pill burden. Results The included cohort (N=24,476) was divided into sub-groups according to adherence in poor-to-moderate (N=6,781) and good adherent patients (N=17,695) with a mean age of 64.8±13.3 and 64.6±11.9 years old, respectively. The Cox’s proportional hazard model showed that good adherence was associated with a relative risk reduction of 23% in all-cause mortality (Table 1A), 21% in all CV events (Table 1B), 17% in ischemic heart disease (Table 1C), 33% in cerebrovascular events (Table 1E), and 22% in the composite outcome of CV events/all-cause mortality (Table 1G). Conclusions The present analysis provided evidence from the Italian real clinical practice that good adherence to PER-based anti-hypertensive therapy results in significantly lower cardiovascular risk and all-cause mortality. These data further emphasize the importance of promoting cost-effective measures to increase medication adherence in patients on anti-hypertensive treatment.

Side branch interventions late after MFM implantation

Abstract Background MFM prostheses were developed for the endovascular treatment of aortic and great vessel aneurysms. Implanted between two healthy segments of arterial vessel, they centralize blood flow and trough Bernoulli's principle. Thereby hemodynamic stress into the aneurismal sac is reduced. Meantime, the porosity along entire prosthesis length preserves all side branches (SB) patent. Results from real clinical practice confirm the high success rate (nearly 100%) of MFM prostheses regarding side branch preservation at one-year follow-up [1,2]. However, late after MFM implantation SB intervention may be required (due to atherosclerosis or others). The access to SB covered by MFM is challenging due to: impossible ostial engagement of the guiding catheter, distance between target vessel ostium and prosthesis, the necessary for all devices used to cross MFM mesh. Materials and methods For the period 2016-2020 we implanted a specific type of MFM prosthesis in order to treat aneurysm of the abdominal aorta in 34 patients. A total of 129 side branches was covered. Within a mean follow-up period of 5 years, 129 side branches were preserved and 7 affected by stenosis or occlusion (two of them asymptomatic). Intervention on the branch covered by the MFM prosthesis was necessary in 5 patients (two males, two females; mean age 68 years). One patient had endovascular celiac trunk stenosis, one patient had both celiac trunk and superior mesenteric artery stenoses, one patient had superior mesenteric artery stenosis, and one patient had left renal artery stenosis. All lesions were intervened through radial or brachial approach. Guiding 6F Judkins right catheter was navigated close to the target branch ostium and the MFM mesh was crossed with .014¨ coronary wire. When guidewire was placed into target vessel small low-profile, coronary balloon is advanced across the mesh of the multilayer stent. Anchor balloon technique was used in order for guiding catheter to cross the mesh gradually. Once the guiding catheter is engaged, the lesion was treated with balloon pre-dilation and implantation of a low-profile, high radial force stent. Results All 4 patients and 5 affected vessels were successfully endovascularly intervened. We did not observe any procedure complications. Immediate resolution of clinical symptoms was achieved. At 1 year follow-up with CT scan all treated branch arteries were patent. Conclusions In patients with previously implanted multilayer stents, the mesh can be crossed safely with readily available coronary devices together with the balloon anchor technique. As such, endovascular treatment of stent-covered visceral and renal arteries is possible without open surgery.Catheter stabilizationSMA successfully treated

Control of arterial hypertension in the context of metabolically-associated disease: challenges and opportunities in Ukraine

Abstract Background/Introduction Arterial hypertension is a prevalent, but modifiable cardiovascular (CV) risk factor. Effective control of blood pressure (BP) is associated with decreased rates of CV morbidity and mortality, as was convincingly demonstrated in randomized clinical trials. There is a substantial gap between BP control in clinical trials and real clinical practice due to multiple factors – e.g. lack of awareness, low medication compliance, side effects of medications, and insufficient availability of medical care – to name the few. The association between poor BP control and metabolically associated disease (MAD) like diabetes and obesity is widely acknowledged and considered the key challenge in effective management of arterial hypertension. Purpose To determine patterns of awareness and control of arterial hypertension in the context of MAD in Ukrainian outpatient patient sample. Methods We enrolled 309 subjects (108 with MAD and 201 without MAD). MAD was defined as the presence of type 2 diabetes and/or overweight/obesity. All subjects were consented for the structured interview and triple sitting BP measurement with an automated device. Results MAD-positive and MAD-negative groups were comparable by age (54.4±1.34 vs 51.8±1.2 years, p=0.29), systolic BP (141.3±2.0 vs 137.4±1.6 mm Hg, p=0.082), diastolic BP (85.2±1.2 vs 82.5±0.9 mm Hg, p=0.13). Presence of MAD was associated with increased odds of having BP&amp;gt;139/89 mm Hg (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.04-2.67, p=0.035), better awareness on hypertension (OR 2.65, CI 1.64-4.28, p=0.0001), and less prevalent normotension (OR 0.51, CI 0.31-0.84, p=0.008). Among MAD-positive patients without history of HTN, 50% actually had elevated office BP, although it did not reach statistical significance as compared to MAD-negative subjects (OR 1.32 CI 0.68-2.56, p=0.42, see Picture 1). Less MAD-positive patients did not take any antihypertensive drugs (37.0% vs 56.7%, difference -19.7%, CI -8.03 to -30.51%, p=0.001), and more of them were taking 3 antihypertensive drugs (17.6% vs 7.5%, difference 10.1% CI 2.58-18.85. p=0.007). Only 53.7% of MAD-positive subjects and 39.8% of MAD-negative subjects claimed they were taking BP-lowering medications on a regular basis (p=0.02). There was no difference in achievement of BP control between MAD-positive and MAD-negative groups (39.2 vs 38.7% for subjects who were aware of HTN, 31.9 vs 31.3% of all hypertensive individuals, p=NS for both). More MAD-positive than MAD-negative subjects admitted they consume alcohol several times per week or daily (22.2 vs 12.4%, p=0.025). Conclusions MAD disease is associated with more prevalent HTN and better awareness on elevated BP. MAD requires more intensive BP-lowering therapy to achieve target BP, but the compliance to medications is suboptimal.Patterns of awareness and BP control

Oldie but Goldie: The Fundamental Role of Radioiodine in the Management of Thyroid Cancer.

Background/Objectives: The management of differentiated thyroid cancer (DTC) patients has undergone a major paradigm shift in past years, especially regarding the role of a careful postoperative disease assessment both in deciding for or against the use of iodine-131 therapy (i.e., patients' selection) and in selecting the correct goal of the treatment: ablative, adjuvant or therapeutic. Furthermore, diagnostic and risk-oriented uses of iodine isotopes (i.e., 123/124/131I) should always be considered during both postoperative assessment and follow-up of DTC patients to improve early staging and response assessment to initial treatments, respectively. The present review summarizes current (and real-life-related) evidence and the emerging perspectives on the therapeutic, diagnostic, and theragnostic use of radioiodine isotopes. Methods: A review of the pertinent literature was performed in PubMed, Web of Science, and Scopus without language restrictions or time limits and using one or more fitting search criteria and terms. Results: According to the literature evidence and real-life clinical practice, a risk-oriented postoperative iodine-131 therapy remains pivotal for most DTC patients and improves early disease staging through post-therapy functional imaging (i.e., theragnostic aim). Accordingly, the goal of iodine-131 therapy, the optimal strategy (empiric vs. dosimetric approach), the appropriate stimulation method [i.e., levothyroxine (L-T4) withdrawal vs. recombinant human thyrotropin (rhTSH) administration] and, finally, the suggested radioiodine activity to deliver for iodine-131 therapy (RIT) should be personalized, especially in metastatic DTC patients. Conclusions: The evidence related to the diagnostic and theragnostic use of iodine isotopes leads to a significant improvement in the postoperative risk stratification and staging of DTC patients in addition to a more accurate assessment of the response to initial treatments. In conclusion, radioiodine is really an oldie but goldie radiotracer. It has both a current fundamental role and a future perspective for the more careful management of DTC patients.

Assesment of factors for late diagnosis of idiopathic pulmonary arterial hypertension in real clinical practice

Idiopathic (primary) pulmonary arterial hypertension – a rare progressive disease that shortens life, usually diagnosed at a late stage. Therefore, it is critical to have a low threshold for suspicion of pulmonary hypertension (PH) and to refer patients to specialized centers for diagnostic evaluation and treatment as early as possible. Echocardiography is the method of choice for pulmonary hypertension assessing. Aim of the study. To determine the reason for the late diagnosis of idiopathic pulmonary arterial hypertension.Material and methods. Using the developed questionnaire, 41 patients, men and women aged 18 years and older, who were reliably diagnosed with idiopathic pulmonary arterial hypertension, were interviewed.Results and discussion. The diagnosis of idiopathic pulmonary arterial hypertension in clinical practice is made on average 7.1±6.0 years from the onset of the first symptoms of the disease. In 95% of cases, the onset of idiopathic pulmonary arterial hypertension begins with shortness of breath on exertion. Most often, the development of the disease was preceded by an acute respiratory viral infection. All patients underwent diagnostic echocardiography at the time of their first visit, but the diagnosis was established in only 56% of patients.Conclusions. Reasons for late diagnosis of idiopathic pulmonary arterial hypertension: the nature of the disease at its onset and errors in diagnosis.