Oncologic Outcomes of Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma Initially Managed with Chemoradiation.

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan-Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11-47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5-66.5%), 54.5% (95% CI 44.4-66.8%), and 26.8% (95% CI 18.6-38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16-46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99-42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05-6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

Anal Adenocarcinoma Treated in the Era of Total Neoadjuvant Therapy and Nonoperative Management.

BACKGROUND: Anal adenocarcinoma bears a treatment strategy unique to other anal cancers. OBJECTIVE: This study aimed to describe oncologic outcomes of total neoadjuvant therapy followed by watch-and-wait approach for anal adenocarcinoma. DESIGN: Retrospective analysis. SETTINGS: This study was conducted at a comprehensive cancer center. PATIENTS: Patients with anal adenocarcinoma treated between 2004 and 2019 were selected. INTERVENTIONS: Fifty-four patients received neoadjuvant therapy and were divided into 2 groups according to their treatment strategy: total neoadjuvant therapy versus single neoadjuvant modality therapy. MAIN OUTCOME MEASURES: Organ preservation, tumor regrowth, local failure, distant metastasis rates, recurrence-free survival, and overall survival. RESULTS: This study included 70 patients with anal adenocarcinoma. Fifty-four patients (77%) received neoadjuvant therapy, of whom 30 (42%) received total neoadjuvant therapy and 24 (34%) received single neoadjuvant modality. Twenty-three (33%) patients achieved complete clinical response and were managed by watch-and-wait approach. The proportion of patients able to continue to watch-and-wait approach was higher after receiving total neoadjuvant therapy (60%) compared with single neoadjuvant modality therapy (20%; p = 0.004). A tumor regrowth rate of 22% was observed in the total neoadjuvant therapy group. The 5-year overall survival rate was 70% (95% CI, 59%-83%), including 61% (95% CI, 42%-88%) for the total neoadjuvant therapy and 65% (95% CI, 48%-88%) for the single neoadjuvant modality groups. Colostomy was avoided in 50% of patients who received total neoadjuvant therapy and 83% of watch-and-wait patients. Five-year recurrence-free survival rates of 55% (95% CI, 39%-79%) and 30% (95% CI, 15%-58%) were observed in the total neoadjuvant therapy and single neoadjuvant modality groups. LIMITATIONS: Retrospective nature. CONCLUSIONS: This is the first report in the literature describing the safety and feasibility of nonoperative management for anal adenocarcinoma. Anal adenocarcinoma treated with total neoadjuvant therapy and nonoperative management achieve regrowth rates comparable to those observed in rectal cancer, with oncologic outcomes similar to those of traditional treatment strategies. See Video Abstract . ADENOCARCINOMA ANAL TRATADO EN LA ERA DE LA TERAPIA NEOADYUVANTE TOTAL Y EL TRATAMIENTO NO QUIRRGICO: ANTECEDENTES:El adenocarcinoma anal conlleva una estrategia de tratamiento único para otros cánceres anales.OBJETIVO:Describir los resultados oncológicos de la terapia neoadyuvante total seguida de observar y esperar en adenocarcinoma anal.DISEÑO:Análisis retrospectivo.AJUSTE:Este estudio se llevó a cabo en un centro oncológico integral.PACIENTES:Se seleccionaron pacientes con adenocarcinoma anal tratados entre 2004-2019.INTERVENCIONES:Cincuenta y cuatro pacientes recibieron terapia neoadyuvante y se dividieron en dos grupos según su estrategia de tratamiento: terapia neoadyuvante total versus terapia de modalidad neoadyuvante única.PRINCIPALES MEDIDAS DE RESULTADO:Preservación de órganos, recurrencia tumoral, falla local, tasas de metástasis a distancia, libre de recurrencia y supervivencia general.RESULTADOS:El estudio incluyó a 70 pacientes con adenocarcinoma anal. Cincuenta y cuatro pacientes (77%) recibieron terapia neoadyuvante, de los cuales 30 (42%) recibieron terapia neoadyuvante total y 24 (34%) recibieron modalidad neoadyuvante única. Veintitrés (33%) pacientes presentaron una respuesta clínica completa y fueron tratados con vigilancia y espera. La proporción de pacientes capaces de continuar en observar y esperar fue mayor después de recibir terapia neoadyuvante total (60%) en comparación con la terapia de modalidad neoadyuvante única (20%) ( p = 0,004). Se observó una tasa de recurrencia tumoral del 22% en el grupo de terapia neoadyuvante total. La tasa de supervivencia general a 5 años fue del 70% (IC95% 59%-83 %), incluido el 61% (IC95% 42%-88%) para la terapia neoadyuvante total y el 65% (IC95% 48%-88%) para grupos de modalidad neoadyuvante única. Se evitó la colostomía en el 50% de los pacientes que recibieron terapia neoadyuvante total y el 83% de los pacientes en observar y esperar. Se observaron tasas de supervivencia libre de recurrencia a cinco años del 55% (IC95% 39%-79%) y del 30% (IC95% 15%-58%) en los grupos de terapia neoadyuvante total y modalidad neoadyuvante única, respectivamente.LIMITACIONES:Diseño retrospectivo.CONCLUSIONES:Este es el primer informe en la literatura que describe la seguridad y viabilidad del tratamiento no quirúrgico del adenocarcinoma anal. El adenocarcinoma anal tratado con terapia neoadyuvante total y manejo no quirúrgico logra tasas de recurrencia comparables a las observadas en el cáncer de recto, con resultados oncológicos similares a las estrategias de tratamientos tradicionales. (Traducción-Dr. Fidel Ruiz Healy ).

Concurrent immunotherapy and re-irradiation utilizing stereotactic body radiotherapy for recurrent high-grade gliomas.

BACKGROUND: Clinical trials evaluating immune checkpoint inhibition (ICI) in recurrent high-grade gliomas (rHGG) report 7%-20% 6-month progression-free survival (PFS), while re-irradiation demonstrates 28%-39% 6-month PFS. AIMS: We evaluate outcomes of patients treated with ICI and concurrent re-irradiation utilizing stereotactic body radiotherapy/fractionated stereotactic radiosurgery (SBRT) compared to ICI monotherapy. METHODS AND RESULTS: Patients ≥18-years-old with rHGG (WHO grade III and IV) receiving ICI + SBRT or ICI monotherapy between January 1, 2016 and January 1, 2019 were included. Adverse events, 6-month PFS and overall survival (OS) were assessed. Log-rank tests were used to evaluate PFS and OS. Histogram analyses of apparent diffusion coefficient maps and dynamic contrast-enhanced magnetic resonance perfusion metrics were performed. Twenty-one patients with rHGG (ICI + SBRT: 16; ICI: 5) were included. The ICI + SBRT and ICI groups received a mean 7.25 and 6.2 ICI cycles, respectively. There were five grade 1, one grade 2 and no grade 3-5 AEs in the ICI + SBRT group, and four grade 1 and no grade 2-5 AEs in the ICI group. Median PFS was 2.85 and 1 month for the ICI + SBRT and ICI groups; median OS was 7 and 6 months among ICI + SBRT and ICI groups, respectively. There were significant differences in pre and posttreatment tumor volume in the cohort (12.35 vs. 20.51; p = .03), but not between treatment groups. CONCLUSIONS: In this heavily pretreated cohort, ICI with re-irradiation utilizing SBRT was well tolerated. Prospective studies are warranted to evaluate potential therapeutic benefits to re-irradiation with ICI + SBRT in rHGG.

Time to administration of stereotactic radiosurgery to the cavity after surgery for brain metastases: a real-world analysis.

OBJECTIVE: Publications on adjuvant stereotactic radiosurgery (SRS) are largely limited to patients completing SRS within a specified time frame. The authors assessed real-world local recurrence (LR) for all brain metastasis (BM) patients referred for SRS and identified predictors of SRS timing. METHODS: The authors retrospectively identified BM patients undergoing resection and referred for SRS between 2012 and 2018. Patients were categorized by time to SRS, as follows: 1) ≤ 4 weeks, 2) > 4-8 weeks, 3) > 8 weeks, and 4) never completed. The relationships between timing of SRS and LR, LR-free survival (LRFS), and survival were investigated, as well as predictors of and reasons for specific SRS timing. RESULTS: In a cohort of 159 patients, the median age at resection was 64.0 years, 56.5% of patients were female, and 57.2% were in recursive partitioning analysis (RPA) class II. The median preoperative tumor diameter was 2.9 cm, and gross-total resection was achieved in 83.0% of patients. All patients were referred for SRS, but 20 (12.6%) did not receive it. The LR rate was 22.6%, and the time to SRS was correlated with the LR rate: 2.3% for patients receiving SRS at ≤ 4 weeks postoperatively, 14.5% for SRS at > 4-8 weeks (p = 0.03), and 48.5% for SRS at > 8 weeks (p < 0.001). No LR difference was seen between patients whose SRS was delayed by > 8 weeks and those who never completed SRS (48.5% vs 50.0%; p = 0.91). A similar relationship emerged between time to SRS and LRFS (p < 0.01). Non-small cell lung cancer pathology (p = 0.04), earlier year of treatment (p < 0.01), and interval from brain MRI to SRS (p < 0.01) were associated with longer intervals to SRS. The rates of receipt of systemic therapy also differed significantly between patients by category of time to SRS (p = 0.02). The most common reasons for intervals of > 4-8 weeks were logistic, whereas longer delays or no SRS were caused by management of systemic disease or comorbidities. CONCLUSIONS: Available data on LR rates after adjuvant SRS are often obtained from carefully preselected patients receiving timely treatment, whereas significantly less information is available on the efficacy of adjuvant SRS in patients treated under "real-world" conditions. Management of these patients may merit reconsideration, particularly when SRS is not delivered within ≤ 4 weeks of resection. The results of this study indicate that a substantial number of patients referred for SRS either never receive it or are treated > 8 weeks postoperatively, at which time the SRS-treated patients have an LR risk equivalent to that of patients who never received SRS. Increased attention to the reasons for prolonged intervals from surgery to SRS and strategies for reducing them is needed to optimize treatment. For patients likely to experience delays, other radiotherapy techniques may be considered.

[68Ga]-DOTATATE PET/MRI as an adjunct imaging modality for radiation treatment planning of meningiomas.

BACKGROUND: Meningiomas express high levels of somatostatin receptor 2 (SSTR2). SSTR2-targeted PET imaging with [68Ga]-DOTATATE can aid with distinguishing residual meningioma from reactive changes in the postoperative setting. We present initial dosimetric analyses, acute events, and local control data utilizing [68Ga]-DOTATATE PET/MRI-assisted target delineation for prospectively-treated intermediate-risk meningiomas. METHODS: Twenty-nine patients underwent DOTATATE PET/MRI meningioma evaluation in 2019. Eight patients with 9 postoperative meningiomas met RTOG 0539 intermediate-risk criteria (recurrent WHO grade I, 1/9; WHO grade II, 8/9). Target volumes were created using DOTATATE PET/MRI to determine residual disease and received a nominal dose of 35.0 Gy over 5 fractions. For comparison, cases were recontoured and planned with MRI alone per RTOG 0539 guidelines. Mean and maximum equivalent 2 Gy doses were generated for target volumes and organs at risk (OAR) within 1 cm of the PTV and compared using Wilcoxon matched pairs signed rank test. RESULTS: DOTATATE PET/MRI-guided planning significantly reduced mean PTV (11.12 cm3 compared to 71.39 cm3 based on MRI alone, P < .05) and mean and max dose to the whole brain, optic nerves, and scalp. PET/MRI plans resulted in at least 50% reduction of mean and max doses to the lens, eyes, chiasm, cochlea, brainstem, and hippocampi. One patient experienced focal alopecia. There were no local recurrences at 6 months. CONCLUSION: Incorporating DOTATATE-PET/MRI for postoperative target delineation in patients with intermediate-risk intracranial meningiomas results in PTV reduction and decreased OAR dose. Our findings warrant larger studies evaluating DOTATATE-PET/MRI in the radiotherapeutic planning of postoperative meningiomas.

Timing of Adjuvant Fractionated Stereotactic Radiosurgery Affects Local Control of Resected Brain Metastases.

PURPOSE: For resected brain metastases (BMs), stereotactic radiosurgery (SRS) is often offered to minimize local recurrence (LR). Although the aim is to deliver SRS within a few weeks of surgery, a variety of socioeconomic, medical, and procedural issues can cause delays. We evaluated the relationship between timing of postoperative SRS and LR. METHODS AND MATERIALS: We retrospectively identified a consecutive series of patients with BM managed with resection and SRS or fractionated SRS at our institution from 2012 to 2018. We assessed the correlation of time to SRS and other demographic, disease, and treatment variables with LR, local recurrence-free survival, distant recurrence, distant recurrence-free survival, and overall survival. RESULTS: A total of 133 patients met inclusion criteria. The median age was 64.5 years. Approximately half of patients had a single BM, and median BM size was 2.9 cm. Gross total resection was achieved in 111 patients (83.5%), and more than 90% of patients received fractionated SRS. The median time to SRS was 37.0 days, and the LR rate was 16.4%. Time to SRS was predictive of LR. The median time from surgery to SRS was 34.0 days for patients without LR versus 61.0 days for those with LR (P < .01). The LR rate was 2.3% with SRS administered ≤4 weeks postoperatively, compared with 23.6% if SRS was administered >4 weeks postoperatively (P < .01). Local recurrence-free survival was also improved for patients who underwent SRS at ≤4 weeks (P = .02). Delayed SRS was also predictive of distant recurrence (P = .02) but not overall survival. CONCLUSIONS: In this retrospective study, the strongest predictor of LR after postoperative SRS for BM was time to SRS, and a cutoff of 4 weeks was a reliable predictor of recurrence. These findings merit investigation in a prospective, randomized trial.

Experimental evolution of external immune defences in the red flour beetle.

The red flour beetle, Tribolium castaneum, secretes quinones that control the microbial flora in the surrounding environment. These secretions act as an external immune defence that provides protection against pathogens. At high concentrations, however, these secretions are harmful to the host itself, and selection may thus have optimized the level of expression under natural conditions. Here, we show that the expression of external immunity responded to selection during experimental evolution within a few generations. At the same time, one component of internal immune defence (phenoloxidase activity) was compromised in beetles selected for either high or low external defences. Intriguingly, offspring protection against a natural pathogen was reduced in flour obtained from beetle lines selected for low amounts of secretions. Altogether, this suggests that external and internal immune defences work together efficiently under natural conditions, whereas every manipulation on the side of external immune defence comes with costs to the internal immune defence.

Male mate choice relies on major histocompatibility complex class I in a sex-role-reversed pipefish.

Mate choice for compatible genes is often based on genes of the major histocompatibility complex (MHC). Although MHC-based mate choice is commonly observed in female choice, male mate choice remains elusive. In particular, if males have intense paternal care and are thus the choosing sex, male choice for females with dissimilar MHC can be expected. Here, we investigated whether male mate choice relies on MHC class I genes in the sex-role reversed pipefish Syngnathus typhle. In a mate choice experiment, we determined the relative importance of visual and olfactory cues by manipulating visibility and olfaction. We found that pipefish males chose females that maximize sequence-based amino acid distance between MHC class I genotypes in the offspring when olfactory cues were present. Under visual cues, large females were chosen, but in the absence of visual cues, the choice pattern was reversed. The use of sex-role reversed species thus revealed that sexual selection can lead to the evolution of male mate choice for MHC class I genes.

No post-conditioning in the human heart with thrombolysis in myocardial infarction flow 2-3 on admission.

AIMS: Proof-of-concept evidence suggests that mechanical ischaemic post-conditioning (PostC) reduces infarct size when applied immediately after culprit coronary artery re-opening in ST-elevation myocardial infarction (STEMI) patients with thrombolysis in myocardial infarction 0-1 (TIMI 0-1) flow grade at admission. Whether PostC might also be protective in patients with a TIMI 2-3 flow grade on admission (corresponding to a delayed application of the post-conditioning algorithm) remains undetermined. METHODS AND RESULTS: In this multi-centre, randomized, single-blinded, controlled study, STEMI patients with a 2-3 TIMI coronary flow grade at admission underwent direct stenting of the culprit lesion, followed (PostC group) or not (control group) by four cycles of (1 min inflation/1 min deflation) of the angioplasty balloon to trigger post-conditioning. Infarct size was assessed both by cardiac magnetic resonance at Day 5 (primary endpoint) and cardiac enzymes release (secondary endpoint). Ninety-nine patients were prospectively enrolled. Baseline characteristics were comparable between control and PostC groups. Despite comparable size of area at risk (AAR) (38 ± 12 vs. 38 ± 13% of the LV circumference, respectively, P = 0.89) and similar time from onset to intervention (249 ± 148 vs. 263 ± 209 min, respectively, P = 0.93) in the two groups, PostC did not significantly reduce cardiac magnetic resonance infarct size (23 ± 17 and 21 ± 18 g in the treated vs. control group, respectively, P = 0.64). Similar results were found when using creatine kinase and troponin I release, even after adjustment for the size of the AAR. CONCLUSION: This study shows that infarct size reduction by mechanical ischaemic PostC is lost when applied to patients with a TIMI 2-3 flow grade at admission. This indicates that the timing of the protective intervention with respect to the onset of reperfusion is a key factor for preventing lethal reperfusion injury in STEMI patients. CLINICAL TRIAL NUMBER: NCT01483755.

[Prehospital treatment with bivalirudin in acute myocardial infarction referred for primary angioplasty. About 152 consecutive patients study]. / Traitement préhospitalier par bivalirudine de l'infarctus aigu du myocarde orienté vers une angioplastie primaire. À propos d'une série consécutive de 152 cas.

OBJECTIVE OF THE STUDY: Bivalirudin, a direct thrombin inhibitor, demonstrated an improvement in the prognosis of acute coronary syndromes by a decrease in major bleeding complications. This observational study evaluated inhospital outcome of patients with acute myocardial infarction treated by prehospital bivalirudin before primary angioplasty. PATIENTS AND METHODS: We included, from June 2010 to June 2012, all patients with acute myocardial infarction receiving prehospital bivalirudin with bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg per hour until the arrival in the catheterization laboratory. Bivalirudin was possibly continued after primary angioplasty. RESULTS: We included 152 patients aged 57.6±11.6 years. A prehospital 60mg loading dose of prasugrel was given in 77% of patients. Coronary angiography with radial access (77.6%) was performed before a successful angioplasty in 97.3% of cases. The bivalirudin infusion was continued after the procedure in 81.6% of patients. Inhospital outcome showed two deaths (1.3%) and two re-infarctions (1.3%) of which one was related to the single acute stent thrombosis (0.6%). Major bleeding complications were limited irrespective of the Gusto (0.6%), Timi (0.6%) or Horizons-MI (4.6%) classification. Bleeding complications rate was similar when bivalirudin was followed or not after primary angioplasty. CONCLUSION: The use of bivalirudin in the prehospital setting for primary angioplasty seems to be effective and safe about ischemic and bleeding complications during the inhospital outcome.

Bateman's principle and immunity in a sex-role reversed pipefish.

In diverse animal species, from insects to mammals, females display a more efficient immune defence than males. Bateman's principle posits that males maximize their fitness by increasing mating frequency whereas females gain fitness benefits by maximizing their lifespan. As a longer lifespan requires a more efficient immune system, these implications of Bateman's principle may explain widespread immune dimorphism among animals. Because in most extant animals, the provisioning of eggs and a higher parental investment are attributes of the female sex, sex-role reversed species provide a unique opportunity to assess whether or not immune dimorphism depends on life history and not on sex per se. In the broad-nosed pipefish Syngnathus typhle, males brood and nourish the eggs in a ventral pouch and thus invest more into reproduction than females. We found males to have a more active immune response both in field data from four populations and also in an experiment under controlled laboratory conditions. This applied to different measures of immunocompetence using innate as well as adaptive immune system traits. We further determined the specificity of immune response initiation after a fully factorial primary and secondary exposure to a common marine pathogen Vibrio spp. Males not only had a more active but also a more specific immune defence than females. Our results thus indeed suggest that the sex that invests more into the offspring has the stronger immune defence.

[Non ST elevation acute coronary syndromes and normal coronary angiography: is it truly good news?]. / Coronarographie normale au cours des syndromes coronariens aigus non ST+: une fausse bonne nouvelle?

Among 10% of all patients presenting with non ST elevation acute coronary syndromes (ACS), coronary angiography do not show non lesions at all (50%) or mild atheromatous stenosis (50%). ACS without angiographic stenosis are more prevalent in female sex and young patients but can be seen in older ones and in men. Pathogenic mechanisms include acute evolution of vulnerable non-significant plaques and endothelial dysfunction. In hospital and mean term prognosis is not as benign as expected. Six months deaths and myocardial infarction incidence is around 6%. Numerous rehospitalizations due to ischemic recurrences are also very often seen. Therefore, such surprising coronary angiograms do not preclude a fair follow-up. These patients need a careful therapeutic strategy.

The stimulation of immune defence accelerates development in the red flour beetle (Tribolium castaneum).

The timing of the transition between life stages is of key importance for an organism. Depending on the environmental conditions, maturing earlier at a smaller size or maturing later at a larger size can be advantageous for fitness. Exposure to parasites and subsequent immune activation may lead to alterations in development. Immune defence often comes at a cost, such as energy drain towards immune function, which is likely to delay development. On the other hand, animals may react to an anticipated risk of infection with a phenotypically plastic shift in life history, which may more likely lead to accelerated development and earlier maturation. We tested these alternatives in the red flour beetle, Tribolium castaneum. Young larvae were exposed to a non-infectious immune challenge with heat-killed bacteria (either Escherichia coli or Bacillus thuringiensis) and they were followed up for their development, survival, adult size and reproduction. We found that animals that had experienced a bacterial challenge developed into adults earlier than sham-treated beetles, while they did not differ significantly in survival or adult size. Beetles exposed to E. coli produced fewer offspring, while exposure to B. thuringiensis did not affect offspring number. Taken together, our results indicate that T. castaneum is able to speed up its development when facing a risk of infection.

[Feasibility and results of transcatheter treatment of patent foramen ovale associated with atrial septal aneurysm. Experience of a general hospital in Mulhouse, France]. / Faisabilité et résultats de la fermeture percutanée des foramens ovals perméables avec anévrisme du septum interauriculaire. Expérience du centre hospitalier général de Mulhouse.

OBJECTIVE: To evaluate the results and the feasibility of the technique of percutaneous closing of patent foramen oval (PFO) with Atrial Septal Aneurysm (ASA) among young patients having presented a cryptogenic cerebral ischemia. PATIENTS AND METHODS: Eighteen patients: 14 cryptogenic stroke and 4 TIA with a broad PFO (rank III) and an important ASA (excursion higher than 15 mm) at transesophageal echocardiography (TEE). The average age is 48.2 years: man 61%, women 39%. The patients have little cardiovascular risk factor (0.83/patient) and 38% presented recurrent thromboembolic events. Percutaneous closing is carried out under general anaesthesia with TEE and Amplatzer devices implantation. A control TEE is carried out 6 months after closing. RESULTS: No complication occurred at the time of the procedures. After 72 hours, one patient presented a major complication: one arteriovenous fistula requiring a surgery. Five patients presented a minor complication: two non complicated femoral hematoma, two atrial arrhytmias and one asymptomatic secondary displacement of the device without need for surgery. Seven-teen patients had TEE at six months: the shunt disappeared for 95% from the patients, no thrombus was found. No recurrent thromboembolic event appeared for the 18 patients (median follow-up 19.2 months). CONCLUSION: The installation of a technique of percutaneous closing of the PFO+ASA is safe and effective.

[Acute myocardial infarction with cardiogenic shock following stress echocardiography: case report]. / Infarctus myocardique aigu compliqué de choc cardiogénique après échocardiographie de stress: à propos d'un cas.

Acute myocardial infarction is a rare complication of dobutamine stress echocardiography (DSE). We report the case of a 60-year-old man with moderate apical sequela of a myocardial infarction (MI) which had an inferior MI complicated with cardiogenic shock and circulatory arrest two hours after a positive DSE in that very circulatory topography. Emergency coronarography objectivizes a dissection of the circumflex artery. The patient required a circulatory assistance device. He survived the episode and left the hospital with 50% left ventricular ejection fraction.

[Acute myocardial infarction in octogenarians treated by primary coronary angioplasty: in hospital outcome, social evolution and long-term mortality. About a forty-seven consecutive patients study]. / Infarctus du myocarde chez l'octogénaire traité par angioplastie primaire: pronostic hospitalier, devenir social et mortalité à long terme. Etude à propos d'une série de 47 patients.

This study evaluated the hospital outcome of octogenarian patients treated by primary angioplasty for acute myocardial infarction less than 12 hours. The long-term mortality and social outcome were evaluated, social outcome was based on IADL and IADL-E scales corresponding to physical autonomy and level of dependence. We included from 1999 to 2005 47 old patients of 83.5+/-3.2 years. The reperfusion of the obstructed coronary artery was obtained in 45 patients (95.7%) with TIMI 3 flow. Hospital mortality was 25.5% and 4.2% without hemodynamic complication. A multivariate analysis identified a Killip score>1 as predictive factor of hospital mortality (OR=8.9 and p=0.05). The long-term survival without death with a follow-up of 26.3+/-18.3 months was 82.2% at 24 months and 70.6% at 48 months according to the Kaplan-Meier method. In an multivariate analysis, hospitalization exit without aspirine was associated with a higher long term mortality (OR=34.8 and p=0.04). According to the evolution of scores of IADL and IADL-E scales, patients had an excellent autonomy and good capacities before the infarction and they kept them on the long term. Thus octogenarians with acute myocardial infarction treated by primary angioplasty have a high in hospital and long term mortality but the survivors preserve an excellent daily autonomy.

[Heart failure and myocardial infarction in the elderly. For its more specific management]. / Insuffisance cardiaque et infarctus myocardique chez le sujet âgé. Pour une prise en charge plus déterminée.

UNLABELLED: TWO NEGATIVE FACTORS: Heart failure, whether present during the first hours of myocardial infarction, whether it worsens or whether it occurs during the first days, or persists during the acute phase, is a highly unfavourable predictive factor of hospital mortality and mortality secondary to myocardial infarction. Furthermore, old age is the most negative predictive factor of late mortality following myocardial infarction. THERAPEUTIC IMPLICATIONS: These two negative predictive elements that considerably enhance immediate and secondary mortality after myocardial infarction, notably when they are combined, require more specific and voluntary management (in terms of medical--thrombolysis, beta-blockers, CEI--and interventional treatments) in these patients. THE NEED TO EXTEND THE INDICATIONS: Since the efficacy of these medical treatments and myocardial revascularisation techniques (during the acute phase in the case of contraindication for thrombolysis or during the secondary phase) is even greater, in terms of immediate and secondary mortality after myocardial infarction in patients at high risk (elderly patients and those suffering from heart failure), it would appear essential to widen their indications to this group of patients in whom the spontaneous prognosis is worst.

[Epidemiology and prognosis of cardiac insufficiency]. / Epidémiologie et pronostic de l'insuffisance cardiaque.

Cardiac insufficiency, the outcome in the majority of cardiac diseases, is common and serious. The frequency is rising, and the fatality, even if it has diminished thanks to various treatments, remains elevated. The epidemiology of cardiac insufficiency is relatively little known in France, despite its considerable economic impact on the health system, while this constraint is ever increasing. Some significant French statistics: the number of cardiac insufficiency cases is about 500,000, there are 120,000 new cases each year. The incidence rises from 4@1000 of males and 3@1000 of females aged between 55 and 64 years to 50@1000 of males and 85@1000 of females aged 85 to 94 years. The average age for occurrence of cardiac insufficiency is 73.5 years; two thirds of patients are over 70 years. There are about 3.5 million consultations and 150,000 hospitalizations for cardiac insufficiency every year. The average length of stay is 11 days. There are more than 32,000 deaths annually from cardiac insufficiency. The costs linked to cardiac insufficiency represent more than 1% of total medical costs. Cardiac insufficiency is a major problem for public health, and it is more and more so. This must prompt us to treat our patients better, and to undertake more preventive measures.