Real-life Patients Research Articles

Differences in clinical features of patients with heart failure and reduced, mildly reduced, and preserved ejection fraction in a contemporary cohort: is the clinical profile changing?

Abstract Introduction Heart failure is a serious health problem and continues to have a high mortality and incidence of decompensations, despite advances in its management. The type of HF, defined by the LVEF value, has a great influence on treatment, since not all drugs and procedures have been shown to improve prognosis in the different subtypes of HF (reduced-HFrEF, mildly reduced-HFmrEF, and preserved-HFpEF). In addition, there are differences in clinical characteristics and comorbidities that may also influence these aspects, although the demographic and social changes that have occurred in recent years may have changed this perspective. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the differences in clinical and demographic characteristics and comorbidities among the three subtypes of HF. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1716 patients with HF included between 2019 and 2021 by 45 specialized HF units accredited by the SEC. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. The clinical and demographic characteristics and comorbidities of the patients were compared according to the type of HF. Results Of the 1716 patients, 55.5% were HFrEF, 11.9% HFmrEF and 32.6% HFpEF. Figure 1 shows the main demographic and cardiovascular characteristics of the three subgroups. The median LVEFs were 30% (23-35), 45% (42-48) and 58% (53-65), respectively. Figure 2 shows the prevalence of major comorbidities. Patients with HFpEF were older and female in higher proportion, and presented a significantly higher prevalence of atrial fibrillation, valvular heart disease, obesity, hypertension, and anemia. Patients with HFrEF had a higher prevalence of coronary artery disease, smoking, admissions for HF in the previous year, and left bundle branch block. There were no differences between the three groups in the remaining comorbidities, including chronic kidney disease and chronic respiratory diseases. The characteristics of HFmrEF were intermediate between HFrEF and HFpEF (figures 1 and 2). Conclusions In our contemporary cohort of real-life HF patients, slight differences were observed between the 3 types of HF, particularly in relation to age, proportion of women, and prevalence of cardiac diseases. However, the prevalence of most of the major comorbidities did not show significant differences between the 3 groups, suggesting that a shift toward greater similarity in clinical characteristics between the 3 types of HF may be occurring.

Heart failure and advanced chronic kidney disease: differences in characteristics, treatment and outcomes in patients with glomerular filtration rate greater or less than 30 ml/minute/m2

Abstract Introduction Heart failure (HF) is a serious health problem and continues to have a high mortality and incidence of decompensation, despite advances in its management. Chronic kidney disease (CKD) is very prevalent in patients with HF, hinders their treatment and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate-GFR <30 ml(min/m2). It is important to know the differential characteristics of these patients to improve their management. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the differences in clinical characteristics and treatment between patients with HF and advanced CKD. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1716 patients with HF included between 2019 and 2021 by 45 specialized HF units accredited by the SEC. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. The clinical and demographic characteristics and comorbidities of the patients were compared according to GFR < or > 30ml/min/m2. Results Of the 1,716 patients, 11.1% had a GFR<30 and 88.9% >30 mL/min/m2. Figure 1 shows the main clinical characteristics and comorbidities of the 2 groups. Median LVEF was similar in both groups: 42 (30-58) vs 38% (29-54). The group with advanced CKD was older (77±9.6 vs 70.5±12.6 years; p<0.001), had greater HF severity (more admissions for HF in the last year, worse NYHA functional class and longer evolution time), and a higher prevalence of coronary heart disease, hypertension, diabetes mellitus, cognitive impairment, anemia, iron deficiency and hyponatremia. There were no differences in sex, BMI, serum potassium or other comorbidities (Figure 1). Figure 2 shows the treatment received in each group. Patients with GFR <30 received in a significantly lower proportion all drugs for HF (p<0.001), except diuretics and potassium binders (ACEI/ARA, sacubitril-valsartan, MRA, beta-blockers, digoxin and SLGT2 inhibitors), and less cardiac rehabilitation (5.2 vs 10.4%; p=0.029). Incidence of one-year mortality was significantly higher in patients with GFR<30 ml/min/m2 (37.2 vs 14.4 per 100 persons-year, p<0.001), as were HF hospitalizations (61.3 vs 33.0; p<0.001) and HF decompensations without hospitalization (24.1 vs 11; p<0.001). Conclusions In our contemporary cohort of real-life HF patients, the prevalence of advanced CKD was 11.1%. These patients had a higher severity of HF, despite which, the utilization of HF drugs, including SGLT2 inhibitors was much lower than in those with GFR >30 ml/min/m2. One-year mortality, HF hospitalization and HF decompensations were almost 3-times higher. This treatment trend needs to be modified to improve the prognosis of these patients.

Differences in the optimization of pharmacological treatment in patients with heart failure and reduced ejection fraction and advanced chronic kidney disease

Abstract Introduction Chronic kidney disease is very prevalent in patients with HF, makes their treatment difficult and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate <30 mL/min/m2). Renal insufficiency increases the risk of drug intolerance and an increase in serious side effects, which can lead to underuse, with consequent negative effects on patient prognosis. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the achievement of dose targets for the most used drugs in HF with reduced ejection fraction (HFrEF) and the impact of advanced CKD. Methods We analyzed 914 patients with HFrEF consecutively included between 2019 and 2021 in the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology in 45 centers. We evaluated the proportion of patients treated with ACEI, ARA, ARNI, MRA, beta-blockers and SGLT2 inhibitors at the registry inclusion visit, the causes of non-prescription, and the achievement of the maximum dose recommended in the ESC clinical practice guidelines or the maximum tolerated dose in these patients, comparing the GFR groups, greater or less than 30 ml/min/m2. Results Of the 914 patients, 8.9% had a GFR<30 mL/min/m2. Their age was 76.9±9.7 years, 39.7% women, mean LVEF 32.8±9-6%. Patients with GFR<30 received in a significantly lower proportion all HF drugs except diuretics, ARBs and potassium chelators: sacubitril-valsartan 30.5% vs 59.2%; MRAs 31.7 vs 77.8%; SGLT2 inhibitors 34.1 vs 52.9% (p<0.001; Figure 1). The main reason for non-use was intolerance/contraindication for beta-blockers and "other" for the rest of the drugs (Figure 1). The proportion of patients in whom the maximum recommended, or maximum tolerated dose was reached was low in both groups, less than 40-50% for all drugs except MRA. There were no significant differences between the two groups in relation to the degree of renal dysfunction, although there was a tendency for the recommended doses to be obtained more frequently in the group with lower GFR (Figure 2). Conclusions In our contemporary cohort of real-life patients with HFrEF and advanced CKD, the use of recommended drugs for HF was significantly lower than in those patients with better renal function. However, where they were used, maximum recommended or tolerated doses were achieved in a higher proportion of patients. This indicates that with adequate selection it is possible to achieve the objectives proposed by the clinical practice guidelines in this complex group of patients.

Effectiveness of anti-IL5/5Rα biologics in severe asthma in real world studies: a systematic review and meta-analysis

BackgroundThree biologics targeting interleukin 5 (anti-IL5) or its receptor-α (anti-IL5Ra) are approved for patients with severe asthma.MethodsWe conducted a systematic search until May 1, 2023, to identify observational studies and non-randomised trials that assess the response to anti-IL5/5Rα of real-life patients with severe eosinophilic asthma in MEDLINE and EMBASE. We performed random-effects meta-analyses.ResultsWe identified 6,401 studies of which 92 with 9546 patients were analysed. Biologics use was associated with 62% reduction in severe exacerbations (risk ratio, RR, 0.38, 95%CI 0.29 to 0.50) and 54% reduction in hospitalisations (RR 0.46, 95%CI 0.35 to 0.61) at 12 months of treatment, compared to pre-treatment. Biologics improved asthma control [decrease in asthma control questionnaire (ACQ) by 1.11 points (95%CI −1.29 to −0.94) and increase in asthma control test (ACT) by 6.41 points (95%CI 5.66 to 7.16)], and increased the asthma quality of life questionnaire (AQLQ) by 1.08 points (95%CI 0.88 to 1.28) and forced expiratory volume in 1 s (FEV1) by 0.21 L (95% CI 0.15 to 0.27) at 12 months. There was a significant reduction in oral corticosteroids use by 51% (RR 0.49, 95%CI 0.42 to 0.56), with a mean dose reduction of 6.01 mg/d (95%CI −7.55 to −4.48) at 12 months of treatment. Similar findings were observed at 3–4, 6 and 24 months. Biomarker-related response to treatment was also noted.ConclusionsThis comprehensive meta-analysis summarises the significant clinical response to anti-IL5/5Rα biologics in real-life studies, providing important insights for clinical practice use of these agents.

Why do physicians practice osteopathic manipulative treatment (OMT)? A survey study.

Few osteopathic physicians (Doctors of Osteopathic Medicine [DOs]) utilize osteopathic manipulative treatment (OMT) in their clinical practice, although all DOs are trained to do so. The reasons why many do not utilize OMT are not entirely clear. Anecdotally, these authors have observed that if a physician utilizes OMT, it is because they witnessed the efficacy for themselves in real-life clinical diagnoses found on patients or volunteers. This study seeks to explore this phenomenon. This study seeks to explore the relationship between witnessing the efficacy of OMT and the future use of OMT in clinical practice. Surveys were sent to DOs who work with Des Moines University's College of Osteopathic Medicine (COM) clinical students as well as osteopathic medical students enrolled at the Des Moines University's COM. Survey data were analyzed by separating physicians into cohorts based on their use of OMT and students into cohorts based on their interest in utilizing OMT in future practice. DOs who practice OMT reported at least one, and often multiple, instances of witnessing the efficacy of OMT on real-life patients or volunteers while in their first 2 years of medical school. Those who do not utilize OMT reported few opportunities to witness the efficacy of OMT on a real-life patient. For physicians, 96.1 % of those who utilize OMT in their practice had the opportunity to see it work positively during the first 2 years of medical school, whereas only 7.4 % who do not utilize OMT had the opportunity. These findings are mirrored in the experience of current osteopathic medical students who are interested and uninterested in utilizing OMT in their future practice. These findings emphasize the importance of exposing our medical students to some type of 'real-life' experience early in their careers; the data show that these experiences can be very beneficial in expanding the interest in utilizing osteopathic manipulative medicine (OMM) in future practice. COMs can consider the implementation of programs that provide this experience to students, including extracurricular activities dedicated to the use of OMT.

Mask side-effects are related to gender in long-term CPAP: results from the InterfaceVent real-life study

BackgroundOver the past three decades, our understanding of sleep apnea in women has advanced, revealing disparities in pathophysiology, diagnosis, and treatment compared to men. However, no real-life study to date has explored the relationship between mask-related side effects (MRSEs) and gender in the context of long-term CPAP.MethodsThe InterfaceVent-CPAP study is a prospective real-life cross-sectional study conducted in an apneic adult cohort undergoing at least 3 months of CPAP with unrestricted mask-access (34 different masks, no gender specific mask series). MRSE were assessed by the patient using visual analog scales (VAS). CPAP-non-adherence was defined as a mean CPAP-usage of less than 4 h per day. The primary objective of this ancillary study was to investigate the impact of gender on the prevalence of MRSEs reported by the patient. Secondary analyses assessed the impact of MRSEs on CPAP-usage and CPAP-non-adherence depending on the gender.ResultsA total of 1484 patients treated for a median duration of 4.4 years (IQ25–75: 2.0–9.7) were included in the cohort, with women accounting for 27.8%. The prevalence of patient-reported mask injury, defined as a VAS score ≥ 5 (p = 0.021), was higher in women than in men (9.6% versus 5.3%). For nasal pillow masks, the median MRSE VAS score for dry mouth was higher in women (p = 0.039). For oronasal masks, the median MRSE VAS score for runny nose was higher in men (p = 0.039). Multivariable regression analyses revealed that, for both women and men, dry mouth was independently and negatively associated with CPAP-usage, and positively associated with CPAP-non-adherence.ConclusionIn real-life patients treated with long-term CPAP, there are gender differences in patient reported MRSEs. In the context of personalized medicine, these results suggest that the design of future masks should consider these gender differences if masks specifically for women are developed. However, only dry mouth, a side effect not related to mask design, impacts CPAP-usage and non-adherence.Trial Registration: InterfaceVent is registered with ClinicalTrials.gov (NCT03013283).First registration date is 2016–12-23.

Description of Baseline Quality of Life in Patients Diagnosed with Metastatic Renal Cell Carcinoma

Introduction: Renal cancer (RC) is not typically symptomatic until it reaches a considerable size and an advanced stage [World J Oncol. 2020;11(3):79–87]. The 5-year survival rate for metastatic renal cancer (mRC) is estimated at 13% [CA Cancer J Clin. 2021;71(1):7–33]. Health-related quality of life (HRQoL), obtained as patient-reported outcomes (PRO), reflects the patient’s subjective perception of the disease and treatment impact on their normal activity and well-being [Lancet Oncol. 2016;17(11):e510–4]. Measuring HRQoL can facilitate doctor-patient communication, aid in decision-making, and improve clinical outcomes [Eur Urol Focus. 2020;6(1):26–30]. We will analyse the baseline quality of life of patients diagnosed with mRC, who are candidates for systemic treatment, in our setting, as measured by responses to the NCCN-FKSI 19 questionnaire. Methods: We analysed 78 consecutive patients diagnosed and treated for mRC from September 2012 to September 2019. We described the baseline questionnaire responses of our patients before initiating systemic treatment and analysed their responses. Results: Over 60% of the patients reported some degree of lack of energy or fatigue, 60.8% were very or extremely worried about their disease worsening, and 47.9% had some issues related to rest. Additionally, 26.8% of the patients were not at all satisfied with their quality of life at that time. Conclusions: Patients diagnosed with mRC exhibit deterioration in their quality of life, mostly showing asthenia and concern about their disease. The quality of life of “real-life patients” seems to be worse than that of those included in clinical trials.

Overexpression of CCL-20 and CXCL-8 genes enhances tumor escape and resistance to cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with locally advanced and metastatic cutaneous squamous cell carcinoma

ABSTRACT Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed. We enrolled 81 patients with a median age of 82 years. After 16.4 months of median follow-up, 12- and 24-months PFS were 53% and 42%, respectively; while 12- and 24-months OS were 71% and 61%, respectively. Treatment was well tolerated. Overall response rate (ORR) was 58%, with a disease control rate (DCR) of 77.8%. The difference between genes expressed in responder versus non-responder patient samples was substantial, particularly for genes involved in immune system regulation. Cemiplimab-resistant tumors were associated with over-expression of CCL-20 and CXCL-8. Cemiplimab confirmed efficacy and safety data in real-life cSCC patients. Overexpression of CCL-20 and CXCL-8 could represent biomarkers of lack of response to immunotherapy.

Apixaban Versus Vitamin K Antagonists in Patients With Antiphospholipid Syndrome: A Cohort Study.

Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in patients with APS on apixaban versus vitamin K antagonists (VKA). We enrolled 152 patients with APS (aged 44 years [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target international normalized ratio [INR] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism, ischemic stroke, or myocardial infarction, along with major bleeding. We observed 4 thrombotic events (6.1%, 3 venous thromboembolism and 1 ischemic stroke) in patients on apixaban and 12 events (14%, 9 venous thromboembolism, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. Patients with APS on apixaban had similar risk of recurrent thromboembolism compared with those on warfarin (hazard ratio [HR] = 0.327, 95% confidence interval [CI]: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs. 50%, P = 0.01) and more frequently in triple-positive APS (50% vs. 22.1%, P = 0.028) and in patients with higher D-dimer at baseline ( P = 0.023); the latter difference was present in the apixaban group ( P = 0.02). Patients on apixaban had similar risk of major bleeding compared with warfarin (HR = 0.54, 95% CI: 0.201-1.448). In real-life patients with APS, apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some patients with APS could be treated with apixaban.

Impact of universal immunization program with monoclonal antibody nirsevimab on reducing the burden of serious bronchiolitis that need pediatric intensive care.

Nirsevimab appears to have an important impact on reducing the number and length of stay of PICU admissions due to RSV bronchiolitis. • Bronchiolitis is the mostcommon viral infection of the lower respiratory tract in infants. • It represents 13% of the total pediatric intensive care admissions, typically during winter. This is one of the causes that produces a collapse in the health care systems all around the world. • In October 2023, universal immunization with monoclonal antibody nirsevimab of all children under 6 months of age was started in the majority of autonomous communities in Spain. • Recent publications from the nirsevimab clinical trials have evidenced a high RSV protective effect, but data on its effect on real life patients who require pediatric intensive care unit admission are missing.

Arthralgia and myalgias associated with aromatase inhibitors: Frequency and characterization in real-life patients.

e12504 Background: Adjuvant treatment with aromatase inhibitors (AI) in estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer (BC) has been shown to increase overall survival (OS). However, arthralgias and myalgias are common adverse effects in patients treated with AI. Objective: To evaluate the frequency and characteristics of arthralgias and myalgias in patients with early BC, treated adjuvantly with AI at the Mastology Unit of the Oncology Service of the Hospital de Clínicas and the Soriano Departmental Hospital. Methods: A prospective, cross-sectional, descriptive study was conducted. A questionnaire was administered to the patients to assess the presence and characteristics of arthralgias and myalgias associated with AI. Statistical analysis: "Age" was described using measures of central tendency and dispersion. Qualitative variables were presented in absolute and relative frequencies. Logistic models were used to assess the association between patient, tumor, and treatment characteristics and the presence of pain. Results: Results were presented using Odds Ratio and p-value, using R software (version 4.1.2) with a significance threshold of 5%. 83 patients were included, with a median age of 69 years. 75.9% presented treatment-related arthralgias and/or myalgias, with an average intensity of 5 to 7. 80.9% received NSAIDs, achieving satisfactory analgesia. The presence of arthralgias and myalgias was significantly associated with age and time since last menstruation, being more frequent in patients over 50 years old and those with more than 5 years since the last menstruation. Conclusions: Approximately 70% of the patients presented arthralgias or myalgias. These findings suggest a possible role of estrogen withdrawal in their development mechanism. It is crucial to carry out multidisciplinary and translational research to evaluate the etiology and therapeutic options for patients with AI-related arthralgia.

Ischaemic and haemorrhagic risk distribution in real-life patients with acute coronary syndromes

Background Effective treatment of non-ST-segment elevation acute coronary syndromes (NSTEACS) requires careful assessment of both ischaemic and bleeding risks. We aimed to analyse risk distribution and evaluate antiplatelet prescription behaviours in real-life settings. Methods Data from 1100 NSTEACS patients in Buenos Aires, Argentina, from the Buenos Aires I Registry, with a 15-month follow-up, were analysed. In-hospital and 6-month GRACE scores, CRUSADE, and Precise DAPT scores were calculated. Results The mean age was 65.4 ± 11.5 years with a majority being male (77.2%). In-hospital mortality was 2.7%, primarily due to cardiovascular causes (1.8%). Bleeding events occurred in 20.9% of patients, with 4.9% classified as ≥ BARC 3. Predominance of low bleeding (71.3%) and ischaemic (55.8%) risks on admission was observed. At 6 months, the low-risk Precise category (70.9%) and GRACE (44.1%) categories prevailed. Linear correlation analysis showed a moderately positive correlation (r = 0.61, p < .05) between ischaemic–haemorrhagic risks. Regarding the prescription of antiplatelet agents, in the low ischaemic–haemorrhagic risk group, there was a predominance of aspirin + clopidogrel (41.2%) over other high-potency antiplatelet regimens (aspirin + ticagrelor or prasugrel). In the low ischaemic and high haemorrhagic risk group, aspirin and clopidogrel were also predominant (58%). Conclusions Our analysis underscores the significant relationship between ischaemic and haemorrhagic risks during NSTEACS hospitalisation. Despite the majority of patients falling into the low-intermediate risk category, the prescription of P2Y12 inhibitors in real-life settings does not consistently align with these risks.

#2119 Long-term efficacy of tolvaptan therapy in patients with ADPKD

Abstract Background and Aims Currently, the only available therapy to ameliorate disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) is tolvaptan, a vasopressin V2 receptor antagonist. Real-life data on tolvaptan treatment effect is sparce, with several limitations including restricted follow-up, relatively small patient groups, no control groups, or only data reported on kidney function without total kidney volume. We studied, therefore, the long-term effect of tolvaptan on kidney function as well as kidney growth in a relatively large number of real-life ADPKD patients and controls. Moreover, we investigated the effect of salt and protein intake on long-term treatment efficacy. Method Data from two national ADPKD cohorts were pooled. Kidney function (creatinine-based eGFR) was measured at least yearly and total kidney volume (TKV, measured by MRI or CT) at least 3-yearly. Salt and protein intake were measured by 24 h urine excretion. To investigate the long-term effects of tolvaptan we assessed change in eGFR and TKV before as well as after start of tolvaptan using linear mixed effects models. For this purpose, we excluded the acute treatment effect from start to 6 months after initiation of tolvaptan. As a control group, we included all patients who were not treated with tolvaptan, assessing change in eGFR and TKV before and after the theoretical start of treatment (based on the average time of tolvaptan initiation observed in the tolvaptan-treated group) as well as a matched control group. Subgroup analyses of salt and protein intake were based on the median urinary excretion of sodium or urea. Results 697 patients (47 ± 12 years, 59.1% female) were included, of which 104 patients used tolvaptan. Mean duration of tolvaptan use was 6.0 ± 4.5 years (range: 0.8 to 15.6). Tolvaptan use reduced yearly eGFR decline by 17.4% (−4.43 to −3.66 mL/min/1.73 m2/year, p = 0.03, number of measurements: n = 817), whereas in the non-tolvaptan control group after the theoretical start of treatment, eGFR decline increased by 13.3% (−1.95 to −2.21 mL/min/1.73 m2/year, p = 0.2, n = 2804). Long-term TKV growth did not change after start of tolvaptan treatment (4.90 to 5.53%/year, p = 0.5, n = 316). Similar results were obtained in the matched control group. A more substantial treatment effect of tolvaptan on eGFR slope was noted in patients with high compared to low salt intake (assessed as ≥ versus &amp;lt; median urinary sodium excretion of 146 mmol/24 h (difference 1.62 (0.22 to 3.02) mL/min/1.73 m2/year, p = 0.02). Subgroup analysis according to median protein intake did not show a significant difference in tolvaptan treatment effect. Conclusion In this study, with real-life patient data, long-term follow-up, and a control group, we found that tolvaptan attenuated long-term kidney function decline but, notably, did not influence kidney growth. Higher daily salt intake was associated with a more substantial tolvaptan treatment effect, perhaps due to higher vasopressin levels before treatment, and consequently more vasopressin antagonism by tolvaptan.

Development of a bio-inspired wound model for debridement training

Wound debridement is commonplace in expediting wound healing in the clinic. Despite this, there are limited resources available for simulation training for practitioners prior to facing real-life patients. Typically, citrus peels or porcine skin are employed in a vain attempt to improve debridement proficiency, yet these fail to provide a realistic experience of the textures and consistencies of wounds. Therefore, there is a clear unmet need for a safe and effective tool that can facilitate hands-on learning under the instruction of an experienced debrider. To fill this niche, a life-like wound model was designed and developed, featuring leathery necrotic eschar, an intermediary sloughy layer, and a rough granulation tissue in the bottommost layer, all within a healthy skin base. The healthy tissue portion of the model was designed to exhibit similar mechanical properties to those found in human skin. Likewise, the sloughy layer was viscous enough to remain within the model under static conditions yet could be removed using any appropriate debriding tool synonymous with real slough. Mechanical testing of the necrotic eschar revealed brittle fracture behaviour, akin to what is observed in patients. Each layer of the wound model provided the visual and haptic feedback of how it would look and feel to debride a patient’s wound in the clinic, giving invaluable experience for potential trainees in a safe and effectual way. It is envisaged that these models can be developed in a personalised way to suit the individual needs of the user, such as incorporating underlying models of bone or tendon, while retaining the key elements of the wound, which make it successful. This model is proposed as an important step forward in bridging the gap between becoming a newly qualified debriding practitioner and encountering the first wound in the clinic, subsequently improving the confidence of the debrider and enhancing patient outcomes.

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients

Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

Arthralgia and myalgia associated with aromatase inhibitors: frequency and characterization in real-life patients.

Adjuvant treatment with aromatase inhibitors (AI) in oestrogen receptor-positive and/or progesterone receptor-positive breast cancer (BC) has been shown to increase overall survival. However, arthralgias and myalgias are common adverse effects in patients treated with AI. To evaluate the frequency and characteristics of arthralgias and myalgias in patients with early BC-treated adjuvantly with AI in the Mastology Unit of the Oncology Service of the Hospital de Clínicas and the Departmental Hospital of Soriano. A prospective, cross-sectional and descriptive study was performed. A questionnaire was administered to patients to assess the presence and characteristics of arthralgias and myalgias associated with AI. 'Age' was described with measures of central tendency and dispersion. Qualitative variables were presented in absolute and relative frequencies. Logistic models were used to evaluate the association between patient characteristics, tumour characteristics, treatment characteristics and the presence of pain. Results were presented by odds ratio and p-value, using R software (version 4.1.2) with a significance threshold of 5%. 83 patients were included, with a median age of 69 years. 75.9% presented arthralgias and/or myalgias related to treatment, with an average intensity of 5-7. 80.9% received non-steroidal anti-inflammatory drugs (NSAIDs), achieving satisfactory analgesia. The presence of arthralgias and myalgias was significantly associated with age and time since the last menstrual period (LMP), being more frequent in patients older than 50 years and those with more than 5 years since the LMP. Approximately 70% of the patients presented arthralgias or myalgias. These findings suggest a possible role of oestrogen withdrawal in its mechanism of development. Multidisciplinary and translational research is crucial to evaluate the ethology and therapeutic options for patients with AI-related arthralgia.

Real-world experience with pertuzumab and trastuzumab combined with chemotherapy in neoadjuvant treatment for patients with early-stage HER2-positive breast cancer: the NEOPERSUR study

PurposeHER2-targeted therapies have dramatically improved outcomes of patients with HER2-positive breast cancer (BC), as demonstrated in neoadjuvant trials. This study aims to provide real-world evidence on the use and effectiveness of combined pertuzumab, trastuzumab and chemotherapy (CT) in early-stage HER2-positive BC.MethodsA retrospective, multicentre study was conducted on patients diagnosed with HER2-positive early BC treated with neoadjuvant pertuzumab and trastuzumab plus CT at 13 Spanish sites. The primary endpoint was pathological complete response (pCR).ResultsA total of 310 patients were included. Pertuzumab and trastuzumab were combined with anthracyclines and taxanes, carboplatin and docetaxel, and taxane-based CT in 77.1%, 16.5%, and 6.5% of patients, respectively. Overall, the pCR rate was 62.2%. The pCR was higher amongst patients with hormone receptor-negative tumours and with tumours expressing higher levels of Ki-67 (> 20%). After postoperative adjuvant treatment, 13.9% of patients relapsed. Those patients who did not achieve pCR, with tumours at advanced stages (III), and with node-positive disease were more likely to experience distant relapse. Median overall survival (OS) and distant disease-free survival (D-DFS) were not reached at the study end. The estimated mean OS and D-DFS times were 7.5 (95% CI 7.3–7.7) and 7.3 (95% CI 7.1–7.5) years, respectively (both were significantly longer amongst patients who achieved pCR). Grade 3–4 anti-HER2 related toxicities were reported in six (1.9%) patients.ConclusionNeoadjuvant pertuzumab and trastuzumab plus CT achieve high pCR rates in real-life patients with HER2-positive early BC, showing an acceptable safety profile. Innovative adjuvant strategies are essential in patients at high risk of distant disease recurrence.

Intracranial Efficacy of Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel in Real-World Patients with Non-Small-Cell Lung Cancer and EGFR or ALK Alterations.

Contrary to Pemetrexed-containing chemo-immunotherapy studies, Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel (ABCP) treatment has consistently shown clinical benefit in prospective studies in patients with lung cancer and actionable mutations, where intracranial metastases are common. Here, we aimed to describe the real-life population of patients fit to receive ABCP after targeted therapy and quantify its clinical effect in patients with brain metastases. Patients treated in Cheshire and Merseyside between 2019 and 2022 were identified. Data were collected retrospectively. A total of 34 patients with actionable EGFR or ALK alterations had treatment with a median age of 59 years (range 32-77). The disease control rate was 100% in patients with PDL1 ≥ 1% (n = 10). In total, 19 patients (56%) had brain metastases before starting ABCP, 17 (50%) had untreated CNS disease, and 4 (22%) had PDL1 ≥ 1%. The median time to symptom improvement was 12.5 days (range 4-21 days), with 74% intracranial disease control rates and 89.5% synchronous intracranial (IC) and extracranial (EC) responses. IC median Progression Free Survival (mPFS) was 6.48 months, EC mPFS was 10.75 months, and median Overall Survival 11.47 months. ABCP in real-life patients with brain metastases (treated or untreated) was feasible and showed similar efficacy to that described in patients without actionable mutations treated with upfront chemo-immunotherapy.

Impact of diagnostic investigations in the management of CAR T-cell–associated neurotoxicity

AbstractInternational guidelines regarding the management of immune effector cell–associated neurotoxicity syndrome (ICANS) recommend several diagnostic investigations, including magnetic resonance imaging (MRI), lumbar puncture (LP), and electroencephalogram (EEG) based on ICANS grade. However, the impact of these investigations has not yet been evaluated. Here, we aimed to describe the role of MRI, LP, and EEG in the management of ICANS in a cohort of real-life patients treated with chimeric antigen receptor (CAR) T cells at the University Hospital of Rennes, France. Between August 2018 and January 2023, a total of 190 consecutive patients were treated with CAR T cells. Among those, 91 (48%) developed ICANS. MRI was performed in 71 patients (78%) with ICANS, with a therapeutic impact in 4% of patients, despite frequent abnormal findings. LP was performed in 43 patients (47%), which led to preemptive antimicrobial agents in 7% of patients, although no infection was eventually detected. Systematic EEG was performed in 51 patients (56%), which led to therapeutic modifications in 16% of patients. Our study shows that EEG is the diagnostic investigation with the greatest therapeutic impact, whereas MRI and LP appear to have a limited therapeutic impact. Our results emphasize the role of EEG in the current guidelines but question the need for systematic MRI and LP, which might be left to the discretion of the treating physician.

Subclinical atrial fibrillation in embolic stroke of undetermined source: Management and stroke recurrence

Subclinical atrial fibrillation (SAF) represents the most prevalent underlying etiology detected after an embolic stroke of undetermined source (ESUS). Investigating SAF is strongly recommended during the diagnostic work-up. The efficacy of oral anticoagulant (OAC) therapy in reducing the risk of stroke recurrence post-SAF detection remains a conundrum. Thus, our study aimed to analyze the management of secondary antithrombotic prophylaxis and the rate of 12-month stroke recurrence in real-life ESUS patients. We retrospectively analyzed clinical, radiographic, and echocardiographic findings of patients with ESUS who underwent non-implantable 2-week electrocardiogram (ECG) monitoring after discharge. Episodes of SAF of any duration were considered diagnostic. Antithrombotic treatment at hospital discharge and after ECG monitoring, as well as 12-month recurrence, were registered. We compared the rate of stroke recurrence between patients with and without detection of SAF. One hundred and fifty-nine patients (75 females) with a median age of 73.5 (interquartile range [IQR] = 66.75 &amp;ndash; 79) years represented the study population. At hospital discharge, 96.9% of patients received antiplatelet therapy as secondary antithrombotic prophylaxis. SAF was detected in 82 patients (51.5%), and OAC was prescribed in 98.6% of them. The median time from stroke onset to OAC prescription was 143 (IQR = 94 &amp;ndash; 178) days. Overall, 12-month stroke recurrence occurred in eight patients (5%). The stroke recurrence rate was lower in patients prescribed OAC compared with those not prescribed it, although the difference was not significant (3.7% vs. 6.25%; P = 0.7202). In our study, OACs prescribed post-SAF detection in patients with ESUS reduced, but not significantly, the risk of stroke recurrence. Future research and prospective multicenter studies are warranted.