Impact Of Therapeutic Strategies Research Articles

Long-Term Outcome of Multiple Myeloma Patients Receiving Autologous Stem Cell Transplantation (ASCT) - Impact of Therapeutic Strategy Following ASCT

Introduction Despite all the therapeutic progress made in multiple myeloma (MM), the standard of care for eligible patients remains an intensive induction therapy followed by high dose melphalan and autologous stem cell transplantation (ASCT). Material and methods This present retrospective study included MM patients treated in Lyon between 1997 and 2020. All patients received induction chemotherapy followed by intensive chemotherapy and ASCT, with or without consolidation and maintenance therapy. Number and type of therapeutic lines administered for relapse after ASCT were analyzed. All data were reported in the European blood and marrow transplantation (EBMT) PROMISE registry. Statistical analysis Descriptive analyses were used for demographic variables, biological parameters, and treatment characteristics. Overall survival (OS) and progression-free survival (PFS) were presented using the Kaplan-Meier method and log-rank tests were performed to compare survival curves. Univariate and multivariate analyses were computed using Cox regressions and the multivariate analyses considered the variables for which the univariate ANOVA p-value was≤ 10%. Statistical analyses and graphics were computed with R v4.1.2, with the help of ‘survival’ and ‘ggplot2‘ packages. Results Before ASCT A total of 342 patients were included in the study (median 60 years (range: 28-73), 58% were male, 89.4% were diagnosed with a type III myeloma according to the Salmon and Durie classification. No genetic analysis was performed at that time. Most patients (92.5%) had a performance status (PS) of 0 or 1. The type of myeloma was heavy chain and light chain myeloma for 75.7% patients (68.9% of IgG kappa) and light chain myeloma in 23.1%. The median delay between diagnosis and ASCT was 4.8 months. Before ASCT, patients received an induction therapy with VTD in 54.1% of cases, VD in 30.1%, and more recently VRD in 16.1%. Disease status before ASCT was complete remission (CR) for 17.5% of the patients, partial remission (PR) and very good partial remission (VGPR) for 79.2% of patients and progressive disease or relapse for 3.0% of them. After ASCT The median duration of aplasia was 11 days. At day 100, the response was CR in 166 patients (50.5%), 182 patients (54.7%) received a consolidation treatment and 71 patients (20.8%) a maintenance therapy (Revlimid® for 90% of them). Overall, 227 (66.4%) patients relapsed. The median delay between ASCT and relapse was 22.5 months (0.89-229.13) and the median follow-up duration was 46.7 months (0.33-287.97). Among the 227 patients who relapsed, 6 patients were not treated, 79 patients (23.1%) received one chemotherapy line, 32 patients (9.4%) received two lines, 38 (11.1%) received 3 and 72 (21.1%) received at least 4 lines and up to 8. Overall survival and progression free survival The median OS was 132 [95% CI 110.6; NR] months from diagnosis and 122.8 [100.9; NR] months from ASCT. The median PFS was 39.35 [36.25; 43.37] months from diagnosis and 31.07 [28.42; 35.91] months from ASCT (Figure 1 A, B). In multivariate analysis on OS, the shorter aplasia duration (p<0.001) and consolidation and maintenance (p<0.001) were significantly associated with a significant better OS. The median OS was not reached from ASCT for patients who have received both consolidation and maintenance treatments and no death was reported. (Figure 1 C). For patients receiving chemotherapy lines for relapses after ASCT (Figure 1D) regardless of the number of lines the median OS was102.4 months and the 10-year OS probability was 45.6%. The OS of patients who received 3 lines of treatment was identical to that of patients who received one or 2 lines after ASCT. The median OS after 1 to 2 lines of chemotherapy after ASCT was not reached and was 127.15 months [70.6-NR] for those receiving 3 lines (Figure 4B). The OS of patients who received more than 4 chemotherapy lines after ASCT was significantly lower compared to the OS (p=0.0096) with a median [95%CI] OS of 85.5 months [65.61-106.15]. In conclusion this study showed the significant positive impact on OS of the association consolidation and maintenance. We have also studied the impact of number of chemotherapy lines and the impact on OS and PFS of kind of treatment will be discussed.

Impact of therapeutic strategy on disease‐free and overall survival of early‐stage cervical cancer: Surgery alone versus preoperative radiation

There is no international consensus for management of early-stage cervical cancer (ESCC). This study aimed to retrospectively investigate disease-free survival (DFS) and overall survival (OS) in patients with ESCC according to the therapeutic strategy used, surgery alone versus preoperative radiation following by surgery. Data were retrospectively collected from 1998 to 2015 using the Gynecological Cancer Registry of the Côte d'Or. The inclusion criteria were FIGO 2018 ≤ IB2; squamous cell carcinoma, adenocarcinoma or adenosquamous type. Survival curves were compared using the log-rank test. One hundred twenty-six patients were included. Median survival was 90 months. There was no significant difference in DFS (HR = 0.91, 95%CI [0.32-2.53], p = 0.858) or in OS between surgery alone versus preoperative radiation following by surgery (HR = 0.97, 95%CI [0.31-2.99], p = 0.961). In the subgroup of patients with stage ≥IB1, there was no significant difference in DFS (HR = 3.26, p = 0.2) or in OS (HR = 3.87, p = 0.2). Our study did not identify any difference in survival according to the treatment strategy. Preoperative radiation following by surgery can be an alternative to surgery alone for ESCC.

Impact of therapeutic strategy on disease-free and overall survival of early-stage cervical cancer: Surgery alone versus preoperative radiotherapy.

e17517 Background: At present, there is no international consensus for management of early-stage cervical cancer. This study aimed to retrospectively investigate disease-free survival (DFS) and overall survival (OS) in patients with early cervical cancer according to the therapeutic strategy used, surgery alone versus pre-operative radiotherapy following by surgery. Methods: Data from patients with early-stage cervical cancer were retrospectively collected from January 1998 to December 2015 using the Breast & Gynecological Cancer Registry of the Côte d’Or, regrouping data from 7 centers. The inclusion criteria were: FIGO 2009 stage IB1 or lower; epidermoid, adenocarcinoma or adenosquamous type. The exclusion criteria were: history of pelvic radiation; concomitant radiochemotherapy; adjuvant radiotherapy; total radiation dose less than 50 Gy, or more than 66 Gy or not documented. In the surgery group, patients had only a surgical treatment for early-stage cervical cancer. The surgical treatment was either a hysterectomy, a trachelectomy or a conization. In the radiation group; patients had radiotherapy, brachytherapy and/or radiotherapy followed by surgery. DFS and OS were determined using the Kaplan-Meier method .Survival curves were compared using the log-rank test. Results: A total of 126 patients were included. Median survival in the whole population was 90 months (47-148); 72 months for those receiving primary surgery, and 135.5 months for those receiving primary radiation therapy. There was no significant difference in DFS between the surgery and radiation groups (HR=2.82, 95%CI (0.82-9.65), p=0.08). Similarly, there was no significant difference in OS between groups (HR=1.35, 95%CI (0.6-3.05), p=0.5). In the sub-group of patients with stage IB1 (FIGO 2009), there was no significant difference in DFS (HR=3.26, 95%CI (0.4-26.76), p=0.2) or in OS (HR=3.87, 95%CI (0.49-30.35), p=0.2) between groups. Conclusions: Cervical cancer counts among the only solid tumors for which increasing mortality has been observed in recent years. Radiation therapy is still a major source of morbidity for young patients. Therefore, key issues remain outstanding for the future management of young patients with cervical cancer and include reducing the morbidity of existing therapeutic options by identifying subgroups of patients at low or intermediate risk, and facilitating fertility-sparing surgery.

Clinical and Microbiological Characteristics of Neonates with Candidemia and Impacts of Therapeutic Strategies on the Outcomes.

Neonatal candidemia is associated with significant morbidities and a high mortality rate. We aimed to investigate the clinical characteristics of Candida bloodstream infections in neonates and the impact of therapeutic strategies on the outcomes. We identified all the neonates with candidemia from a medical center in Taiwan over an 18-year period (2003–2021) and analyzed them. Clinical isolates were confirmed by DNA sequencing, and antifungal susceptibility testing was performed. The prognostic factors associated with clinical treatment failure (30-day, all-cause mortality and persistent candidemia > 72 h after antifungal agents) and in-hospital mortality were analyzed using logistic regression modeling. A total of 123 neonates with 139 episodes of candidemia were included in the study. The median (IQR) gestational age and birth weight of the neonates with candidemia were 29.0 (26.0–35.0) weeks and 1104.0 (762.0–2055) g, respectively. The most common Candida spp. was Candida albicans (n = 57, 41.0%), followed by C. parapsilosis (n = 44, 31.7%), Candida guilliermondii (n = 12, 8.6%), and C. glabrata (n = 11, 7.9%). The overall susceptibility to fluconazole was 81.3%, and the resistant rates against other antifungal agents were less than 3%. The cumulative mortality rate at 7 and 30 days after the first episode of candidemia was 11.3% and 32.3%, respectively. The overall in-hospital mortality rate was 42.3%. The treatment outcomes did not change over the study period and were not affected by delayed initiation of antifungal agents. Multivariate analysis showed that delayed catheter removal (odds ratio [OR], 5.54; 95% confidence interval [CI]: 1.93–15.86, p = 0.001), septic shock (OR, 7.88; 95% CI: 2.83–21.93, p < 0.001), and multiple chronic comorbidities (OR, 8.71; 95% CI: 1.82–41.81, p = 0.007) were independently associated with the final in-hospital mortality. We concluded that the overall mortality of neonatal candidemia has remained consistently high over the past decade. Prompt early catheter removal and an aggressive treatment strategy for neonatal candidemia with septic shock would be critical to improving patient outcomes.

A French National Study on Gastropleural and Gastrobronchial Fistulas After Bariatric Surgery: the Impact of Therapeutic Strategy on Healing.

Gastropleural and gastrobronchial fistulas (GPF/GBFs) are serious but rare complications after bariatric surgery whose management is not consensual. The aim was to establish a cohort and evaluate different clinical presentations and therapeutic options. A multicenter and retrospective study analyzing GPF/GBFs after bariatric surgery in France between 2007 and 2018, via a questionnaire sent to digestive and thoracic surgery departments. The study included 24 patients from 9 surgical departments after initial bariatric surgery (21 sleeve gastrectomies; 3 gastric bypass) for morbid obesity (mean BMI = 42 ± 8kg/m2). The GPF/GBFs occurred, on average, 124days after bariatric surgery, complicating an initial post-operative gastric fistula (POGF) in 66% of cases. Endoscopic digestive treatment was performed in 79% of cases (n= 19) associated in 25% of cases (n= 6) with thoracic endoscopy. Surgical treatment was performed in 83% of cases (n= 20): thoracic surgery (n= 5), digestive surgery (n= 8), and combined surgery (n= 7). No patient died. Overall morbidity was 42%. The overall success rate of the initial and secondary strategies was 58.5% and 90%, respectively. The average healing time was approximately 7months. Patients who had undergone thoracic surgery (n= 12) had more initial management failures (n= 9/12) than patients who had not (n= 3/12), p= 0.001. Complex and life-threatening fistulas that are revealed late require a multidisciplinary strategy. Thoracic surgery should be reserved once the abdominal leak heals; otherwise, it is associated with a higher risk of failure.

Clinical and microbiological characteristics, and impact of therapeutic strategies on the outcomes of children with candidemia

We aimed to determine the clinical and microbiological characteristics of Candida bloodstream infections in children and the impact of therapeutic strategies on outcomes. All pediatric patients with candidemia from a medical center in Taiwan over a 13-year period (2003–2015) were included and a total of 262 patients with 319 episodes of candidemia were analyzed. Overall susceptibility to fluconazole was 86.1%. Cumulative mortality at 7 and 30 days after the first episode of candidemia was 13.4% and 25.2%, respectively. The overall in-hospital mortality rate was 35.1%. The treatment outcomes did not change over the study period. Multivariate analysis showed that delayed catheter removal (odds ratio [OR], 5.52; 95% confidence interval [CI]: 2.97–10.25), septic shock (OR, 5.49; 95% CI: 2.85–10.57), and breakthrough candidemia (OR, 3.66; 95% CI: 1.43–9.35) were independently associated with clinical treatment failure. In children with candidemia, underlying renal insufficiency and hematological/oncological malignancy, delayed catheter removal, and septic shock at onset were independently associated final in-hospital mortality. Analyzing the subgroup of non-neonatal children did not change the findings. We concluded overall mortality of pediatric candidemia remains high during the past decade. Prompt early catheter removal and aggressive treatment strategy in patients with septic shock would be critical to improve outcomes.

Epidemiology and outcome of candidaemia in patients with oncological and haematological malignancies: results from a population-based surveillance in Spain

A prospective, population-based surveillance on candidaemia was implemented in five metropolitan areas of Spain from May 2010 to April 2011. We aimed to describe the distribution and susceptibility pattern of Candida species, and to evaluate risk factors for mortality in patients with oncological (solid tumours) and haematological malignancies. Adults (≥16 years) with cancer were included in the present report. Impact of therapeutic strategies on 7- and 30-day mortality were analysed by logistic regression, adjusting for propensity score by inverse weighting probability of receiving early antifungal treatment and catheter removal. We included 238 (32.6%) patients (195 oncological, 43 haematological). Compared with oncological patients, haematological patients were more likely to have received chemotherapy (53.5% versus 17.4%, p < 0.001) or corticosteroids (41.9% versus 21%, p < 0.001), and have neutropenia (44.2% versus 1.5%, p < 0.001). Overall, 14.8% of patients developed breakthrough candidaemia. Non-albicans Candida species (71.1% versus 55.6%, p 0.056) and Candida tropicalis (22.2% versus 7.6%, p 0.011) were more frequent in haematological patients. Based on EUCAST breakpoints, 27.6% of Candida isolates were non-susceptible to fluconazole. Resistance to echinocandins was negligible. Mortality at 7 and 30 days was 12.2% and 31.5%, respectively, and did not differ significantly between the patient groups. Prompt antifungal therapy together with catheter removal (≤48 hours) was associated with lower mortality at 7 days (adjusted OR 0.05; 95% CI 0.01–0.42) and 30 days (adjusted OR 0.27; 95% CI 0.16–0.46). In conclusion, non-albicans species are emerging as the predominant isolates, particularly in haematological patients. Prompt, adequate antifungal treatment plus catheter removal may lead to a reduction in mortality.

IMPACT of Therapeutic Strategy and Time to Therapy Initiation on Clinical Evolution of Patients with NEWLY Diagnosed Chronic Myelomonocytic Leukemia. a Report from Erasme Study

IntroductionChronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by a heterogeneous clinical and morphological expression that shares features of both myelodysplastic syndromes (MDS) and chronic myeloproliferative disorders. In the last years therapy of CMML has undergone a change with the inclusion of the demethylating agents but data regarding their impact on the “real life” setting are still scarce. The aim of our study was to evaluate the use of the different therapies and the time to therapy in an unselected Spanish population within the ERASME study.Materials and methodsThe ERASME study (CEL-SMD-2012-01) is an observational, post-authorization, prospective, multicenter study that will include a total of 600 patients with MDS and CMML and follow them during a minimum of three years (or until death). The primary objective of this study is to describe the disease progression in routine clinical practice, based on the initial therapeutic strategy, in patients with newly diagnosed MDS and CMML. We present here the results of a pre-specified interim analysis with data of CMML patients enrolled in the ERASME study. Initial patient management strategy is classified in three groups: Observation (OB) & support (SP) (including blood and platelet transfusions and growth factors), active therapy (AT) (including chemotherapy, azacitidine, lenalidomide, etc) and allogenic hematopoietic cell transplant (HCT) (including those patients receiving other therapies before transplant).ResultsA total of 41 CMML patients (34% women) with a median age of 80 years (range 49-91) have been recruited between January 2013-June 2014. The median follow-up time was 6.7 months (range 0.4-15.1). Morphological subtypes according WHO classification were CMML-1 (blasts count <10%) in 35 patients (85%) and CMML-2 (blasts count 10% to 19%) in 6 (15%). According to FAB criteria, 30 patients (73%) had CMML-MD depending on absolute leukocyte count at diagnosis (WBC ≤13x109/L) and 11 (27%) had CMML-MP (WBC >13x109/L).Karyotype was normal in 32 patients (86%). Five patients displayed cytogenetic abnormalities; 3 out of 5 patients with trisomy 8 (isolated or with one additional abnormality). The CMML-GESMD cytogenetic risk classification was low/intermediate/high risk in 83%/10%/5% of patients, respectively. The CPSS was low/int-1/int-2/high in 46%/32%/15%/5% of patients, respectively. Nine out of 41 patients were transfusion dependent at diagnosis.Median bone marrow blast count was 3% (range 0-33). Hemoglobin, platelet and neutrophil count was: 11.1 g/dL (range 7.8-16.7), 106x103/µL (4.2-415), and 3.98x109/L (range 0.48-57.2), respectively. After diagnosis, 33, 7 and 1 of CMML patients were considered candidate to SP/OB, AT and HCT strategy, respectively. The main reasons for treatment selection were risk-disease (90%), symptomatology (83%), age (73%), and comorbidities (46%).The median time to AT initiation from diagnosis for AT/OB&SP was 0.52/2.5 months (range 0.22-2.29) and (range 1.0-4.7) for each group, respectively. Patients in active therapy received azacitidine (n=2, 29%), other low-dose chemotherapy (n=4, 57%) and other therapy (erythropoietin and azacitidine) (n=1, 14%), respectively. Only one patient was considered candidate for HCT and this patient received azacitidine prior the transplant. At last follow-up, a total of 5 (12%) of patients have died (2, 29% of active therapy and 3, 9% of support group) after a median of 3.6 months (range 3.1-4.1) and 1.7 months (range 0.7-10), for each group respectively.ConclusionsCMML patients were treated on an individualized therapy strategy after diagnostic evaluation and prognosis assessment. More data on disease progression in routine clinical practice may be useful in characterizing the newly diagnosed CMML patients. Our prospective study confirms that azacitidine has been considered a therapy for CMML patients, including for HCT candidates. DisclosuresOff Label Use: Vidaza, erythropoietin stimulating agents, revlimid. Valcarcel:Celgene: Honoraria, Speakers Bureau. Rafel:Celgene: Employment. Garcia:Celgene, Novartis: Consultancy, Speakers Bureau.

IMPACT of Therapeutic Strategy and Time to Therapy Initiation on Clinical Evolution in Higher-Risk Myelodysplastic Syndromes. a Report from Erasme Study

IntroductionThe therapy of myelodysplastic syndromes (MDS) has undergone a dramatic change in the last years with the inclusion of the demethylating agents but data regarding their impact on the “real life” setting are still scarce. Moreover the time to therapy from diagnosis, that has been evaluated in acute myeloid leukemia has not formally been evaluated in the MDS. The aim of our study was to evaluate the use of the different therapies and the time to therapy in an unselected Spanish population within the ERASME study. Here we present data from a pre-specified interim analysis of MDS patients who fall into higher-risk categories (Group-2: int-2/high) included in the ERASME study.Materials and methodsThe ERASME study (CEL-SMD-2012-01) is an observational, post-authorization, prospective, multicenter study that will include a total of 600 patients with MDS and Chronic myelomonocytic leukemia (CMML) according to the World Health Organization 2008 classification and that follow them for at least three years (or until death). The primary objective of this study is to describe disease progression in routine clinical practice, based on the initial therapeutic strategy, in patients with newly diagnosed MDS and CMML.The patients are classified in three groups: 1) low/Int-1 IPSS, 2) int-2/high and 3) CMML. Initial patient management strategy is classified in three groups: Observation (OB) & support (SP) (including blood and platelet transfusions and growth factors), active therapy (AT) (including chemotherapy, azacitidine, lenalidomide, etc) and allogenic hematopoietic cell transplant (HCT) (including those patients receiving other therapies before transplant). Initial data from the pre-specified interim analysis are presented.ResultsA total of 87 at int-2/high risk out of 254 MDS patients, 45% women with a median age of 73 years (range 39-87) were recruited between January 2013-June 2014. Of all patients, 57% had int-2 risk and 43% had high risk MDS. Median follow-up was 5.5 months (range 0-14.9). The most common MDS types were refractory anemia excess of blast type 1 and 2 (15% and 67%, respectively) and refractory cytopenia with multilineage dysplasia (16%). Cytogenetic abnormalities were present in 70% of patients (11% complex and 33% very complex Karyotype). Median bone marrow blast count was 12% (range 0-27). Hemoglobin, platelet, and neutrophil count was: 9.5 g/dL (range 6.7-13.3), 65x103/µL (9.7-439), and 1x109/L (range 0-24), respectively. In this patient population, the first therapeutic decision taken by the investigating physician was: AT in 49 (56%), HCT in 18 (21%) and OB&SP in 20 (23%) patients, each one. The main reason for treatment selection were risk-disease disease (94%), age (82%), symptomatology (66%) and comorbidities (55%). Patients in AT received azacitidine (n=44, 90%), chemotherapy plus azacitidine (n=4, 8%) and immunomodulatory therapy (n=1, 2%). Of those patients considered for HCT (n=18), 2 (11%) received transplant without prior therapy, and 16 (89%) received prior therapy with: azacitidine (n=10, 56%) chemotherapy (n=3, 17%), or both in (n=3, 17%). At last follow-up, 8 out of 18 HCT patients had undergone transplant within a median of 9.1 months (range 3.2-11) from diagnosis; 3 patients died before transplant, and 7 are still waiting for transplant. At last follow-up, a total of 26 (30%) have died: 11/6/9 patients for AT/HCT/OB&SP respectively (22%, 33%, 45%) (Log Rank, p= 0.1823). The overall survival was not reached (NR)/11.6/7.89 months (95% CI: 9.86-NR), (95% CI: 5.59-NR) and (95% CI: 2.17-NR), for each group, respectively. The median time from diagnosis to death in each group was 4.2, 4.8 and 2.2 months, respectively.The median time between diagnosis and therapy for AT/HCT/OB&SP was 0.77/0.24/5.3 months (range 0.09-2.75), (range 0.03-2.79), (range 2.2-6.0), for each group, respectively.ConclusionsHigher-risk MDS patients were treated on an individualized therapy strategy after diagnostic evaluation and prognosis assessment. Our prospective study confirms that azacitidine has become the most common therapy for higher-risk MDS patients, including most of HCT candidates. DisclosuresOff Label Use: Vidaza, erythropoietin -stimulating agents, Revlimid. Valcarcel:Celgene: Honoraria, Speakers Bureau. Sanchez:Celgene: Consultancy, Speakers Bureau. Rafel:Celgene: Employment.

Impact of histological variants on the outcomes of nonmuscle invasive bladder cancer after transurethral resection.

The scoring system used after transurethral resection of the bladder (TURB) to guide clinical decision-making regarding nonmuscle invasive bladder cancer (NMIBC) largely assumes that NMIBCs are pure urothelial carcinomas and does not take into account the role of variant histology. This review outlines pathological and clinical characteristics of major histological variants to determine their potential impact in therapeutic strategies for the management of NMIBC. Assessing the presence of histological variants in NMIBCs after TURB currently remains challenging because of limited tissue sample sizes. However, the presence of these variants often indicates poor prognosis with increased risk for recurrence and progression. Among them, only the following histological variants are indications for Bacillus Calmette-Guerin intravesical instillations: squamous or glandular differentiations and deceptively benign or lymphoepithelioma-like carcinomas. However, patients diagnosed with any other variants should be promptly considered for early radical cystectomy, and only those with small cell carcinoma might benefit from neoadjuvant chemotherapy with a neuroendocrine-specific regimen. Based on the available literature (e.g., small case studies and retrospective studies), the existence of histological variants after TURB appears to massively impact NMIBC outcomes.

Determinants of quality of life in patients with atrial fibrillation

Atrial fibrillation (AF) is the most common chronic arrhythmia [1]. Lots of studies focused on the impact of therapeutic strategies on reducing morbidity and mortality in patients with AF [2–4]. However, any therapeutic interventions to control rhythm or rate in patients with AF have not shown to have an impact on mortality or morbidity [2]. Thereafter, it has been suggested that reduction of symptoms and improvement of Quality of Life (QOL) might be better therapeutic target for the management of AF [3].

Impact of Medical Therapy on Atheroma Volume Measured by Different Cardiovascular Imaging Modalities

Atherosclerosis is a systemic disease that affects most vascular beds. The gold standard of atherosclerosis imaging has been invasive intravascular ultrasound (IVUS). Newer noninvasive imaging modalities like B-mode ultrasound, cardiac computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) have been used to assess these vascular territories with high accuracy and reproducibility. These imaging modalities have lately been used for the assessment of the atherosclerotic plaque and the response of its volume to several medical therapies used in the treatment of patients with cardiovascular disease. To study the impact of these medications on atheroma volume progression or regression, imaging modalities have been used on a serial basis providing a unique opportunity to monitor the effect these antiatherosclerotic strategies exert on plaque burden. As a result, studies incorporating serial IVUS imaging, quantitative coronary angiography (QCA), B-mode ultrasound, electron beam computed tomography (EBCT), and dynamic contrast-enhanced magnetic resonance imaging have all been used to evaluate the impact of therapeutic strategies that modify cholesterol and blood pressure on the progression/regression of atherosclerotic plaque. In this review, we intend to summarize the impact of different therapies aimed at halting the progression or even result in regression of atherosclerotic cardiovascular disease evaluated by different imaging modalities.

Lipid lowering targets are easier to attain than those for treatment of hypertension in type 2 diabetes

To assess the impact of therapeutic strategies to reduce cardiovascular risk in patients with type 2 diabetes. Five-hundred patients with type 2 diabetes were studied, using retrospective case note analysis in 1997 (followed by a unit policy targeting vascular risk) and again in 2001. The mean BP of the hypertensive patients was unchanged, 151/83 +/- 23/12 mmHg (1997) and 149/84 +/- 19.1/9.8 mmHg (P=0.2) (2001) (despite increase in patients receiving 23 antihypertensives (4.2% to 18.0%, P<0.01). The mean cholesterol improved from 5.34 +/- 1.1 mmol/L to 4.72 +/- 0.94 mmol/L (P<0.01). 2.9% compared with 44.6% (P<0.01) of hypercholesterolaemic patients, achieved target cholesterol. Antiplatelet therapy increased from 27.6% to 61.2% (P<0.01). Reduced mean HbA1c, 7.91 +/- 1.61% to 7.12 +/- 1.41% (P<0.01). Improved lipid profiles, aspirin uptake and glycaemic control, but no improvement in blood pressure targets were achieved. Additional strategies are required to achieve cardiovascular risk factor targets.

Interleukin-10: An Anti-Inflammatory and Immunosuppressive Cytokine in the Normal and Pathological Immune Response

The immunoregulatory cytokine IL-10 plays a key role in normal and pathological immune responses due to its pleiotropic action on cells of the innate and specific immune system, influencing their differentiation, proliferation and activity. During the immune response an appropriate balance between pro- and anti-inflammatory cytokines, as well as the induction and maintenance of peripheral tolerance are critical. IL-10, mainly produced by antigen presenting and T helper type 2 cells, is engaged in these processes predominantly displaying anti-inflammatory and immunosuppressive properties, but it exerts stimulatory effects as well. The review focuses on the biological activities of IL-10 on cells of myeloid and lymphoid origin and summarizes the current knowledge regarding molecular mechanisms involved in the regulation of IL-10 expression. The pathophysiological role of IL-10 in inflammation and autoimmunity (sepsis, brain-induced immunosuppression, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosis), as well as in allergy and its impact in therapeutic strategies are discussed. Keywords: Interleukin, pathophysiological, rheumatoid

Pathophysiology of Hypertension in the Elderly.

The onset and progression of hypertension is associated with alterations in structure, function, and hemodynamics of the heart, vascular system, and other major organs. An understanding of the structural and functional changes in the cardiovascular system associated with this process would allow for early detection and the development of treatment strategies. In this paper, we focus on the anatomic alterations that accompany vascular aging and the resulting cardiovascular dynamics. Techniques to measure changes in cardiovascular dynamics and left ventricular performance are reviewed. The impact of therapeutic strategies on cardiovascular dynamics and left ventricular function are also discussed. (c)2000 by CVRR, Inc.