Amputation-free survival in the long-term follow-up and gender-related characteristics in patients revascularized for critical limb ischemia.

OBJECTIVE: Patients with Critical Limb Ischemia (CLI) present a high risk of cardiovascular events and death. Revascularization is the cornerstone of therapy to relieve ischemic pain and prevent limb loss. Literature data suggest that women tend to present with worse outcomes after revascularization. The aim of the present study is to determine amputation-free survival in a long-term follow-up in women and men following endovascular revascularization procedure for CLI. METHODS: From November 2013 to December 2020, 357 consecutive patients were retrospectively included. Clinical and biological parameters were recorded at baseline before endovascular revascularization. During follow-up until February 2023, overall survival and amputation-free survival (freedom from major amputation) were analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed to study the parameters associated with amputation-free survival. A P<0.05 was considered as statistically significant. RESULTS: A total of 357 consecutive patients were included, 189 men and 168 women with CLI, with a mean age of 78.6±12 years. Treated hypertension (79%), diabetes mellitus (48%), coronary artery disease (39%) and protein malnutrition (61%) were the most prevalent comorbidities. Women were older than men with a mean age of 82.4±11.4 years (versus 75.4±11 years in men) and presented more frequently with protein malnutrition (70% of women). Prevalence of diabetes, tobacco use and history of coronary heart disease were significantly higher in men. During the 10-year follow-up period, 241 patients had died (68%) and 38 (11%) underwent major amputation, of whom 22 patients were still alive on February 2023. Median survival was 35.5 months [IQR: 29.5; 43] in the overall population, 38.5 [32; 50.4] months in women and 33.5 months [24.7; 43.5] in men. No gender-related differences were noted according to peri-procedural complications, survival probability and amputation-free survival. In multivariate analysis for amputation-free survival, age, previous coronary heart disease, C-reactive protein level, left ventricular ejection fraction (LVEF)<60% and albumin level<35g/L were correlated with poor outcome. In particular, protein malnutrition, as a treatable risk factor, appears significantly correlated with poor outcome in both men and women (HR=2.50 [1.16;5.38], P=0.0196 in men; HR=1.77 [1.00;3.13], P=0.049 in women). CONCLUSION: The present results highlight that mortality in patients after endovascular revascularization remains high with a mortality rate of 28% at 1 year, 40% at 2 years and 51% at 3 years. Women represented a distinct population, almost 10-year older than their male counterparts, with more prevalent protein malnutrition. However, no gender-related difference was noted according to amputation-free survival on the long-term follow-up. Associated risk factors are mainly age, a history of coronary heart disease, pre-procedural inflammatory syndrome and protein malnutrition. Correction of malnutrition could have the potential to improve functional and general long-term prognosis in patients with CLI together with optimal medical and interventional management.

Peri-procedural complications following endovascular revascularization for critical limb ischemia.

OBJECTIVE: Revascularization procedures are considered the cornerstone of therapy in patients with critical limb ischemia (CLI) and multiple procedures are often required to attain limb salvage. The aim of the present study is to determine the prevalence of peri-procedural complications after endovascular procedure, and to determine the clinical and biological characteristics of patients associated to the risk of peri-procedural complications. METHODS: From November 2013 to May 2021, 324 consecutive patients were retrospectively included, of whom 99 underwent more than one revascularization procedure for contralateral CLI or clinical recurrence of CLI. A total of 532 revascularizations were performed. Clinical and biological parameters were recorded at baseline before endovascular revascularization. The occurrence of a peri-procedural complication (local complications, fatal and non-fatal major bleeding or cardiovascular events) was recorded up to 30days after revascularization. Univariate and multivariate analyses were performed to study the parameters associated with per-procedural complications. A P<0.05 was considered as statistically significant. RESULTS: A total of 324 consecutive patients were included, 177 men and 147 women with CLI, with a mean age of 77.6±11.9years. Most of these patients had cardiovascular comorbidities (41% with a history of coronary heart disease, 78% treated hypertensive patients, 49% diabetic patients). Peri-procedural mortality occurred in 13 patients (4%) and 9 patients (2.8%) experienced major amputation at one-month following revascularization. Among the 532 revascularization procedures, 99 major bleeding events (22.8% of the cohort population) and 31 cardiovascular events (8.6% of the cohort population), were recorded in the peri-procedural period. Cardiovascular events were associated with peri-procedural mortality. Complications at the puncture site occurred during 38 of the 532 procedures (10.2% of the cohort population). Compared with patients undergoing a single revascularization procedure, patients with multiple procedures presented a higher risk of major bleeding events (48.5% vs. 11.6%, P<0.0001) and access site complications (20.2% vs. 5.78%, P<0.0001). In multivariate analysis, pulse pressure <60mmHg and hemoglobin level <10g/dl were correlated with the occurrence of major bleeding events; left ventricular ejection fraction<60% and the absence of statin treatment were correlated with the occurrence of cardiovascular complications; a high chronological rank of revascularization was correlated with the occurrence of local complication. Finally, age and gender were not associated with the occurrence of peri-procedural complication. CONCLUSION: The present results highlight that multiple revascularization procedures for limb salvage are required in almost one third of the population with critical limb ischemia and were associated with the risk of major bleeding events and access site complications. The most frequent complications of peripheral vascular interventions were major bleeding events. Adverse cardiovascular events were related with peri-procedural mortality. Anemia, blood pressure, left ventricular ejection fraction and statin treatment are important parameters to consider for peri-procedural outcomes, independently of age, gender and the chronological rank of revascularization procedure.

[French data from the Continuing to Confront COPD (C2C) survey]. / Données françaises dans l'enquête internationale Continuing to confront COPD (C2C).

INTRODUCTION: This article describes the French data which contributed to the international "Continuing to Confront COPD" (C2C) survey conducted in 2013 across 12 countries. Its objective was to describe the characteristics, symptoms and impact of COPD on health status, daily activities and working life in adults identified with the study definition as COPD; i.e., reporting a diagnosis of COPD, emphysema, chronic bronchitis (CB) or symptoms of CB either currently present or for which they had been treated in the past. METHODS: Subjects 40 years or older were screened using random-digit-dialing and those fulfilling the study COPD definition were invited to complete the full survey. RESULTS: The proportion of respondents with COPD (according to study definition) in France was estimated at 7.5%. Among 300 respondents with COPD and complete questionnaire data, 48% were male, 44% aged over 70years, 45% were overweight and 72% had a smoking history. COPD had a severe or very severe impact (COPD assessment test score>20) on health for 43%. Dyspnea (mMRC ≥ 1) was reported by 70% and a limitation of at least 20% of daily activities by 65%. The mean number of exacerbations was 2/year and 16% had been admitted to hospital for respiratory problems during the past year. However, using direct questions, 80% subjects considered that they had mild to moderately severe disease and 78% reported an acceptable health status. CONCLUSION: The impact of COPD is markedly underestimated by respondents with COPD despite a high level of symptoms, poor health status and frequent exacerbations as assessed with validated measures.

[Prevention of venous thromboembolic events by fondaparinux 2.5mg in patients hospitalized for an acute medical illness. ArchiMed Study]. / Prévention des évènements thromboemboliques veineux par fondaparinux 2,5mg chez des patients hospitalisés pour une affection médicale aiguë. Étude ArchiMed. ArchiMed hôpital - étude observationnelle d'usage du fondaparinux 2,5mg en vie réelle ; 718 patients inclus par 107 pharmaciens hospitaliers.

OBJECTIVE: To evaluate the average duration of in-hospital treatment with fondaparinux 2.5mg prescribed for venous thromboprophylaxis in acutely ill medical patients and to describe the treatment population. METHODS: Prospective, observational, national, multicentre, epidemiological study, performed in France at the request of the Transparency Commission of the French National Health Authority (Haute Autorité de Santé). This is part of a larger study program that also included a study with similar design in the general practice setting. The hospital practice part of the study was conducted by hospital pharmacists who were asked to include the first 15 adult subjects hospitalized in a non-surgical ward for whom fondaparinux 2.5mg was initiated for prophylaxis. RESULTS: Fifty-three pharmacists (49.5%) included a total of 718 patients. The average age was 71 ± 16 years (47%<75 years old); 54% were women. For 41% of patients, duration of fondaparinux 2.5mg administration ranged from 6 to 14 days. Eighty-five percent of patients had at least one acute illness related to the prescription of fondaparinux 2.5mg for thromboprophylaxis. Ten percent of the population had at least one risk factor listed on the Case Report Form. Characteristics of patients from the hospital practice study differ from those included in the general practice part of the ArchiMed Study program. CONCLUSION: The hospital practice part of the ArchiMed Study, which is similar to "audits of practices", shows that the real-life conditions of prescription of fondaparinux 2.5mg in patients hospitalized are generally in line with guidelines with respect to indication for thromboprophylaxis in acute medical illness.

Mobilization and collection of peripheral blood stem cells: guidelines for blood volume to process, based on CD34-positive blood cell count in adults and children.

We report 189 mobilizations and 489 collections of peripheral blood stem cells (PBSC) performed in 139 autologous transplantation patients and in 28 donors for allogeneic transplantations whose ages ranged from 2-68 years. We observed a correlation (P < .001; Pearson's coefficient 0.64) between CD34-positive cells and granulocyte-macrophage colony-forming units examined to estimate PBSC. In a subset of 287 collections (97 adults and 49 children) we obtained peripheral blood (PB) CD34-positive cell counts at 2 to 4 hours before leukapheresis. We noted a correlation between PB CD34-positive cell counts before leukapheresis and the number of CD34-positive cells per kilogram of body weight collected in the whole apheresis of the day (P < .001; Pearson's coefficient 0.82). An even better correlation was obtained between PB CD34-positive cells preapheresis and the yield of each individual blood volume (BV) processed (P < .001; Pearson's coefficient 0.87). Healthy donors and patients in each age group behaved similarly. In addition, the collection yield was greater among children than adults. These findings allowed us to develop a simple predictive model to estimate the BV to process for a target dose of CD34-positive cells per kilogram, based on the level of PBSC before apheresis in children and adults.

Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in the acute oral treatment of migraine: a double-blind, randomised, three-attack study.

This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients took at least one dose of study medication (326 took zolmitriptan and 340 took acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2-hour headache response after the first dose for all 3 attacks (the primary end point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p = 0.7228]. For the majority of secondary end points, the two treatments demonstrated comparable efficacy. However, post hoc analysis showed that significantly more patients receiving zolmitriptan were free of pain 2 h after the first dose in all 3 attacks compared with patients receiving acetylsalicylic acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p = 0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free response rate was consistently higher with zolmitriptan (34.6%) than with acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09-1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting, phonophobia and photophobia. There were no important inter-group differences with respect to the onset of meaningful migraine relief, the frequency of headache recurrence, the usage or efficacy of a second dose of medication or the use of escape medication. However, at the last attack, the proportion of patients who expressed overall satisfaction with the treatment was significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340) of those treated with acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and the combination regimen (1.5%); the latter percentage included 1 patient who withdrew from the study due to phlebitis, which was classified as a serious adverse event. This study showed that zolmitriptan is effective and well tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan was at least as effective as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache response, but significantly more effective than the combination therapy for other end points, including the 2-hour pain-free response.

The effect of zafirlukast on repetitive exercise-induced bronchoconstriction: the possible role of leukotrienes in exercise-induced refractoriness.

BACKGROUND: Single doses of zafirlukast attenuate exercise-induced bronchoconstriction (EIB), but previous studies have not measured zafirlukast's effects after regular dosing or its duration of effect beyond 4 hours. OBJECTIVE: The purpose of this study was to assess the effects of zafirlukast 20 mg and 80 mg twice daily compared with placebo on exercise challenges performed at 2 and 8 hours after the last dose of regular administration. METHODS: Twenty-four adult patients with stable asthma taking beta(2)-agonists, inhaled corticosteroids, or both received treatment with zafirlukast (20 mg and 80 mg) and placebo. The patients were treated twice daily for 14 days in a randomized, double-blind, 3-way cross-over fashion, with a 7-day washout period between each treatment. Exercise challenges were performed at 2 and 8 hours after the morning dose on day 14. FEV(1) was measured before exercise and at set intervals after exercise until it returned to within 7% of its baseline value. RESULTS: Both zafirlukast treatments significantly reduced EIB, as measured by the area under the FEV(1) time curve after the 2-hour (P <.001) and 8-hour (P <.001) exercise challenges and maximum fall in FEV(1) at the 2-hour challenge (P <.001). The comparison at 8 hours between treatments was affected by the unexpected finding that EIB was less in the placebo group after the 8-hour challenge than after the 2-hour challenge, as measured by the within-group change in the maximum fall in FEV(1) (P <.001) and the area under the FEV(1) time curve (P =.0023). CONCLUSION: Regular zafirlukast treatment protects against EIB for at least 8 hours after regular dosing. A refractory period, which may be caused by exercise-induced leukotriene release, may last for up to 6 hours after the initial response to exercise.

[Education of patients who have had arterial surgery. Procedure and results]. / L'éducation des opérés artériels. Modalités et résultats.

Teaching preventive measures to patients which have been operated on for arterial diseases with the goal of preventing recurrent lesions or complications related to the surgical procedure itself is an ethical obligation because of its medical and economic consequences. The aim is to convince the patients of the need to change their lifestyle, to consult their physician rapidly in certain precise circumstances, to present regularly for yearly check-ups and sometimes to avoid certain movements or carefully comply to anticoagulant controls. We have had 25 years experience. Oral explanations were complemented early with a booklet given to the patients before discharge. Since 1991, discussion groups are organized each week around a 20-minute film. An audit has shown that about 80% the patients were well informed. Since 1994, the group sessions were held after distributing a questionnaire. Read before the film, it helps the patients become aware of the problems. After the film, each patient raises personal questions in a guided discussion. Since this method has been used, the percentage of well informed patients has risen to 95%. In a very active surgical unit, transmission of information should not be handled to chance. It should be well organized and periodically evaluated. To be effective it should focus on precise goals, be understandable by all, follow a clear presentation of the problems, involve the entire health care team and rely on well prepared support material. Group discussions around a film help to improve patient comprehension and participation. The booklet and the questionnaire will guide the patients when back home.

[Teratogenic effect of pyrimethamine in the rat. In vivo prevention by calcium folinate]. / Effet tératogène de la pyriméthamine chez le rat. Prévention in vivo par le folinate de calcium.

In vivo prevention of malformations induced by pyrimethamine was studied in the rat. The administration of calcium folinate had an almost complete antiteratogenic effect on external, visceral and skeletal malformations, provided that the vitamin was administered together with the pyrimethamine and that the treatment was continued for the following two days.

Pathogenesis of limb and facial malformations induced by pyrimethamine in the rat.

The temporal sequence of morphological events resulting in limb and face malformations was studied in pyrimethamine (PY) treated female rats, 30 mg/kg of PY in a 10 ml/kg suspension of 0.9% NaCl were administered i.p. on days 12, 13 and 14 of gestation. Controls received only 0.9% NaCl solution. The females were killed at different stages of gestation (between 14 and 21 days). Early PY treated embryos showed mainly haematomas in the extremities and the mandibulo-maxillary areas. During the course of gestation, fewer haematomas and more malformations were observed. At term, malformations were observed in the same localisations where haematomas were previously seen.