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Background. Clinical trial demonstrated that SARS-CoV-2 vaccines have the ability of reduce mortality and morbidity due to COVID-19. The aim of this study is to describe the effect of vaccination in term of mortality, type of ventilation and ICU admission among patients hospitalized for COVID-19 from May to December 2021 in a Ligurian Hospital. Methods. This is a retrospective, single-center study conducted in San Martino Hospital (Genoa, Italy), including patients >= 18 years hospitalized for COVID-19 in Infectious Disease and Emergency Units from 1st May to 31st December 2021. We collected demographical data, multimorbidity and disability score, vaccination time ("vaccinated" all patients hospitalized >= 14 days after first dose or >= 7 days after second/ third dose), therapy for COVID-19, mortality at 7 and 30 days, ICU admission, ventilation type. Characteristics of vaccinated (group A) versus non vaccinated (group B) patients were compared using Chi-squared/Fisher's exact test for categorical variables and t-test /Kruskal-Wallis test for the continuous ones. Cox proportional hazards models for death at 30 days were performed as univariate analysis as well as adjusting for age, Cumulative Illness Rating Scale [CIRS], gender, Remdesivir, Monoclonal antibodies, Tocilizumab use. Results. Overall, 405 patients SARS-CoV-2 infected were enrolled. Data about timing of vaccination were available for 360 patients (89%). We compared clinical characteristics and outcomes of group A (32%) versus group B (68%). In group A patients were older (p< 0.001) and frailer (higher CIRS score and lower Barthel index, p< 0.001) than in group B. Among patients requiring oxygen, 76 (31.5%) in group B vs 26 (22.41%) in group A needed high flow ventilation (p=0.036);33 (13.52%) vs 3 (2.59%) respectively were admitted to ICU (Figure 1). Mortality at 30 days after hospitalization was higher in group A at univariate analysis [HR(95%CI) 1.44(0.82;2.53), p=0.208], lower at multivariate analysis [0.57(0.31;1.02), p=0.059]. Conclusion. The results of this study confirm that SARS-CoV-2 vaccination reduces rate of admission to ICU and 30 days mortality among patients hospitalized for COVID-19. In our cohort mortality among vaccinated patients remains high and we hypothesized this is due to high frailty of evaluated population.
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BACKGROUND: New worldwide intensive studies of a new virus called severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) have shown that in its clinical manifestations, the virus has an extremely different expression in different population groups, with age being found to be one of the most common and significant variables. AIM: The objective of this study is to categorize the difference between clinical and laboratory parameters of a sample of patients infected with SARS-COV-2 in the Specialized Hospital for Geriatric and Palliative Medicine "November 13" - Skopje, between survived and deceased patients, impact on the number and severity of comorbidities on the severity of the clinical picture and the survival rate. MATERIALS AND METHODS: In our study, we analyzed data from a sample of 113 patients hospitalized in our institution. The study is cross-sectional and observational, and in the methodology, we analyzed demographic data by gender and age groups, analysis of comorbidities, functional and nutritional status of patients, and risk factors for mortality and survival rate. For this purpose, we used several geriatric scores: Cumulative Illness Rating Scale scale-Geriatric (CIRS-G), degree of functional ability (Bartel), and the Geriatric Nutritional Index (GNRI) score. RESULT(S): The deceased patients had a significantly higher CIRS-G score, while no significant difference in functional (Bartel) and GNRI scores was found. Multivariate regression analysis showed that lymphocytopenia and low saturation were high-risk factors for death in the geriatric population. CONCLUSION(S): Providing hospital-level care for the elderly with SARS-COV-2 contributes to a lower mortality rate. Copyright © 2022 Lidija Veterovska-Miljkovic, Salija Ljatif-Petrushovska, Lazo Jordanovski, Marika Ivanovska, Olivera Bundaleska, Elena Brezovska, Natasha Zdraveska, Emilija Velkova.
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Background: The introduction of venetoclax into clinical practice has improved the outcome of patients with relapsed/refractory chronic lymphocytic leukemia (RR-CLL). The results of the MURANO trial published in March 2018 showed significantly longer progression-free survival (PFS) and overall survival (OS) in RR-CLL patients treated with venetoclax and rituximab (VEN-R) comparing to bendamustine and rituximab (BR) and resulted in the approval of VEN-R in the therapy of RR-CLL in the European Union and the United States. It should be noted that the results of registration studies often do not correspond with the data from real-life observations. Aims: To study the clinical efficacy and safety profile of VEN-R treatment in RR-CLL patients outside clinical trials. Methods: We performed retrospective analysis of RR-CLL patients treated with VEN-R in hematology centers of the Polish Adult Leukemia Study Group (PALG) from 2019 to 2021. Results: Clinical data of 117 RR-CLL patients treated with VEN-R were collected. Median patient age upon initiation of VEN-R therapy was 67 years (range 33 - 84 years). Seventy-two patients (61.5%) were men. Median Cumulative Illness Rating Scale (CIRS) was 6 (range 2 -16). Patients were treated with a median of 2 (range 1-9) previous lines of therapy, whereas 32 patients (27.4%) had relapsed following the first line of treatment. Overall, 25 patients (21.4%) had 17p deletion, whereas TP53 mutation was identified in 13 patients (11.1%). The median follow-up was 9.96 months (range 0.27 -29.13). The overall response rate (ORR) was 95.2%. Seventeen patients (14.5%) achieved complete remission (CR), 83 (70.9%) partial remission (PR), while in 5 patients (4.3%) disease progression was noted. In the patients with 17p deletion (n=22) or TP53 mutation (n=11), CR and PR were observed in 4 (12.1%) and 29 (87.9%) patients, respectively. The median PFS in the whole cohort was 20.8 (95% CI 18.43 -not reached) months and the median OS was not reached. In our study none of the analyzed clinico-pathological factors had significant impact on ORR, PFS and OS. During the follow-up time four (3.4%) cases of Richter transformation were diagnosed. There were 18 deaths recorded during the course of observation;3 (16.7%) due to disease progression and 7 (38.9%) due to COVID-19 infection. The others were due to infections other than SARS-CoV-2 (n=3, 16.7%) and the cause of death could not be specified in five cases (27.8%). Eighty-three patients (70.9%) remain on treatment, while treatment was discontinued in thirty-four cases (29.1%). Reasons for therapy discontinuation included patient's death (52.9%), treatment-related cytopenias (17.6%), disease progression (14.7%), Richter's transformation (11.8%), autoimmune hemolytic anemia (5.9%), diarrhea (2.9%) and infections (8.8%). In one case treatment discontinuation was due to consent withdrawal and one patient was lost to follow-up. The following adverse events of VEN-R treatment were reported during the study: all grade neutropenia (71.8% with grade 3/4 in 55.6%), anemia (51.3%), thrombocytopenia (47%), pneumonia (9.4%), neutropenic fever (6.8%), autoimmune hemolytic anemia (4.3%), immune thrombocytopenic purpura (1.7%), diarrhea (4.3%) and in one case exacerbation of heart failure was observed. Summary/Conclusion: In this retrospective analysis the outcomes of treatment with the VEN-R regimen in real-life setting were worse than those reported in the MURANO trial.
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Introduction: The geriatric patient cohort is at high risk of falling and sustaining a fragility fracture, leading to an admission to the orthopaedic rehabilitation ward. Outbreaks of COVID-19 on wards were a common occurrence, with 13% of cases classified as 'healthcare acquired'. This study examines a group in whom these two scenarios coincided, those who sustained a fragility fracture, and later contracted COVID-19 during their rehabilitation stay. The study aims to identify whether access to orthopaedic rehabilitation services during the acute phase of COVID-19 was associated with better patient outcomes. Methods: A retrospective, cohort observational study was carried out. Data from 26 rehabilitation patients aged over 65 years with confirmed COVID-19 at two Irish orthopaedic rehabilitation wards were collected from health records. Symptom profile, COVID-19 severity level based on Irish Thoracic Society guidelines, Clinical Frailty Scale (CFS), Cumulative Illness Rating Scale-Geriatric (CIRS-G) scores and radiological data were reviewed and compared with outcomes from a similar study carried out in the hospital setting. Results: Patient mortality rate was 7.7% (n = 2) in the orthopaedic rehabilitation population compared to 23.2% (n = 16) in the acute hospital orthopaedic population. Median survivor age was 79.5 years (IQR 70-85.5) and 81.5 years (IQR 76.5-86.5), respectively. Mean CFS was 4.15 (SD 1.6) and 5 (SD 1.6), respectively. Mean CIRS-G scores were 10.6 (SD 4.3) and 8.19 (SD 4.4). Most patients were categorised as mild COVID-19 cases (n = 25, 96%), (n = 56, 81.1%). Eight patients (n = 8, 30.8%) in rehabilitation group were asymptomatic compared to five (n = 5, 7%) in the acute hospital group. Atypical symptom presentation was 15.4% (n = 4) and 7% (n = 5) respectively. Delirium was noted in 11.6% (n = 3) of rehabilitation patients compared to 30.4% (n = 21) of acute patients. Non-invasive ventilation was required in 3.8% (n = 1) of rehab patients and 2.9% (n = 2) of acute hospital patients. Conclusion: Orthopaedic rehabilitation patients were younger, less frail, had a milder COVID-19 disease profile and lower mortality rate when compared with orthopaedic patients in the acute hospital setting. Rehabilitation patients had lower rates of reported delirium. Rehabilitation patients' better outcomes may have been associated with an increased accessibility to allied healthcare, increased time between sustaining a fragility fracture and being diagnosed with COVID-19 and a hospital environment more conducive to recuperation.
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Background: Patients with chronic lymphocytic leukemia (CLL) are known to have a suboptimal immune response of both humoral and cellular arms. Recently, a BNT162b2 mRNA COVID-19 vaccine was introduced with a high efficacy of 95% in immunocompetent individuals. Approximately half of the patients with CLL fail to mount a humoral response to the vaccine, as detected by anti-spike antibodies. Currently, there is no data available regarding T-cell immune responses following the vaccine of these patients. Aim of the study: To investigate T-cell response determined by interferon gamma (IFNγ) secretion in patients with CLL following BNT162b mRNA Covid-19 vaccine, in comparison with serologic response. Methods: CLL patients from 3 medical centers in Israel were included in the study. All patients received two 30-μg doses of BNT162b2 vaccine (Pfizer), administered intramuscularly 3 weeks apart. For evaluation of SARS-CoV-2 Spike-specific T-cell responses, blood samples were stimulated ex-vivo with Spike protein and secreted IFNγ was quantified (ELISA DuoSet, R&D Systems, Minneapolis, Minnesota, USA). T-cell immune response was considered to be positive for values above 25 pg/ml of Spike-specific response. T-cell subpopulations were characterized by flow cytometry (CD3, CD4, CD8). Anti-spike antibody tests were performed using the Architect AdviseDx SARS-CoV-2 IgG II (Abbot, Lake Forest, Illinois, USA). Statistical analysis was performed using Mann-Whitney test for continuous variables while the Wald Chi-square test was used for comparing categorical variables. Results: 83 patients with CLL were tested for T-cell response. Blood samples were collected after a median time of 139 days post administration of the second dose of vaccine (IQ range 134-152). Out of 83 patients, 68 were eligible for the analysis (with positive internal control). Median age of the cohort was 68 years (56-72);and 44 (65%) were males. 19 (28%) patients were treatment-naïve, most of whom were Binet stage A or B. 31 (46%) patients were on therapy: 17 with a BTK-inhibitor, and 13 with a venetoclax-based regimen. 29 (42%) patients were previously treated with anti-CD20, 13 of whom in the 12 months period prior to vaccination. T cell immune response to the vaccine was evident in 22 (32%) patients. CIRS Score>6 and specifically hypertension were statistically significantly associated with a lower T-cell response (univariate analysis, p-value<0.05). Variables that were associated with the development of T-cell response were presence of del(13q), IgM ≥ 40 mg/dL, and IgA ≥ 80 mg/dL (p-value 0.05-0.1). There was no significant difference with regards to age, gender, other CLL-specific prognostic markers, treatment, and T-cell subpopulation distribution according to flow cytometry (Table 1). The presence of T-cell response highly correlated with both the detection of anti-spike IgG antibodies following the second dose (p=0.0239) and at the time of T-cell testing (n=66, p=0.048, Table 2). While 50% of patients who tested positive for anti-spike IgG antibodies also developed positive T-cell response, only 17% of patients who did not develop T-cell response, tested positive for antispike antibodies. Importantly, 24% of the patients who tested negative for anti-spike IgG antibodies, developed positive T cell response. Moreover, the level of the T-cell response (log transformed) correlated linearly with (log transformed) anti-spike IgG titer (adjusted r=0.26 and p =0.026 according to Pearson correlation, Figure 1). Conclusion: We show that cellular immune response to the BNT162b2 mRNA COVID-19 vaccine, is blunted in most CLL patients and that there is a correlation between T-cell response and serologic response to the vaccine. These results need to be validated in a larger cohort.
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Ibrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs. chemo- and/or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited. Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in a real-world setting in Italy in terms of retention rate: the study's primary end point. Methods EVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile. The median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3, 29.7, and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in the TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN =52.1%, R/R = 48.6%), while IGHV was unmutated in 35.0% (TN =33.3% and R/R = 36.15) and mutated in 15.0% (TN =14.6%, R/R = 15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs. R/R 7.27 yrs). At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%;COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%;grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%), and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7 vs. 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts. Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN =8, R/R = 24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%). Permanent discontinuation was observed in 56 (18%) of the pts (TN =17.2%, R/R = 18.7%) and it mostly occurred within the first 6 months. The main causes of discontinuation were toxicity (6.1%), PD (3.8%), and death (3.5%). Temporary interruptions (≤3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN =35.3%, R/R = 27.2%) and 37.7% (TN =37.5%, R/R = 37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment. Finally, in this first IA after 17.3 months (range 1.1-27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2-86.1%] with no difference between TN 83.2% (95% CI, 75.2-89.4%) and R/R 81.2% pts (95% CI, 74.9-86.4%). EVIDENCE is the first realw rld study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL.
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Introduction Ibrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs chemo- and /or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited. Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in real-world setting in Italy in terms of retention rate: the study's primary end point. Methods EVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile. Results The median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3%, 29.7% and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN=52.1%, R/R=48.6%), while IGHV was unmutated in 35.0% (TN=33.3% and R/R=36.15) and mutated in 15.0% (TN=14.6%, R/R=15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs R/R 7.27 yrs). At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%;COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%;grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%) and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7% vs 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts. Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN=8, R/R=24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%). Permanent discontinuation was observed in 56 (18%) of the pts (TN=17.2%, R/R=18.7%) and it mostly occurred within the first 6 months. Main causes of discontinuation were toxicity (6.1%), PD (3.8%) or death (3.5%). Temporary interruptions (≤ 3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN=35.3%, R/R=27.2%) and 37.7% (TN=37.5%, R/R=37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment. Finally, in this first IA after 17.3 months (range 1.1 - 27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2% - 86.1%] with no difference between TN 83.2% (95% CI, 75.2% - 89.4%) and R/R 81.2% pts (95% CI, 74.9% - 86.4%). Conclusions EVIDENCE is the irst real-world study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL. Disclosures: Molica: Janssen: Consultancy, Honoraria;Abbvie: Consultancy, Honoraria;Astrazeneca: Honoraria. Scarfo: Astra Zeneca: Honoraria;Abbvie: Honoraria;Janssen: Honoraria, Other: Travel grants. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation;Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;AbbVie: Consultancy, Honoraria. Frigeri: Celgene: Consultancy, Speakers Bureau;Abbvie: Speakers Bureau;Janssen: Consultancy, Speakers Bureau;Amgen: Speakers Bureau. Sanna: Janssen: Consultancy;Abbvie: Consultancy;Astra Zeneca: Consultancy. Coscia: Janssen: Honoraria, Other, Research Funding;AbbVie: Honoraria, Other;AstraZeneca: Honoraria;Gilead: Honoraria. Reda: Abbvie: Consultancy;Astra Zeneca: Consultancy;Beigene: Consultancy;Janssen: Consultancy. Tafuri: Novartis: Research Funding;Roche: Research Funding;Celgene: Research Funding. Grugnetti: Janssen: Current Employment. Magarotto: Janssen: Current Employment. Mauro: Tskeda: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Speakers Bureau;Abbvie: Consultancy, Honoraria, Speakers Bureau;Roche: Consultancy, Honoraria;Astra Zeneca: Consultancy, Honoraria, Speakers Bureau.