Factors influencing quality of life in children with low-flow vascular malformations: a qualitative study using focus groups.

BACKGROUND: Very few studies have evaluated the quality of life (QoL) of children suffering from low-flow vascular malformations. This is the first study investigating the influencing factors. OBJECTIVES: To identify the factors influencing QoL in children with low-flow vascular malformations. METHODS: We conducted a qualitative study employing focus group interviews (Clinical Trials Number: NCT03440827). The study was a prospective, interventional, non-comparative, multicentre study performed in four expert centres for vascular anomalies. Qualitative data about personal experiences, feelings, difficulties, needs and various factors influencing behaviours were collected. Theme-based content analysis (manual and specialist textural software guided) were used to analyse the verbatim transcripts of all focus group sessions. Manual qualitative discourse analysis was performed to identify the different themes and categories. Informatics' analyses were subsequently performed for each individual category. RESULTS: Ten focus groups (26 individuals including 10 children aged 11 to 15 years) were conducted until saturation. Influencing factors were related to 4 categories: medical care, self-image, social impact on daily activities and challenging social relationships. These factors were responsible for intrafamily upheavals and may lead to future identity-building problems. CONCLUSIONS: This study provides an essential framework from which physicians can develop strategies to improve patient care and quality of life. These data may also be useful to develop specific age-sensitive QoL questionnaires.

Phonon Engineering in Isotopically Disordered Silicon Nanowires.

The introduction of stable isotopes in the fabrication of semiconductor nanowires provides an additional degree of freedom to manipulate their basic properties, design an entirely new class of devices, and highlight subtle but important nanoscale and quantum phenomena. With this perspective, we report on phonon engineering in metal-catalyzed silicon nanowires with tailor-made isotopic compositions grown using isotopically enriched silane precursors (28)SiH4, (29)SiH4, and (30)SiH4 with purity better than 99.9%. More specifically, isotopically mixed nanowires (28)Si(x)(30)Si(1-x) with a composition close to the highest mass disorder (x ∼ 0.5) were investigated. The effect of mass disorder on the phonon behavior was elucidated and compared to that in isotopically pure (29)Si nanowires having a similar reduced mass. We found that the disorder-induced enhancement in phonon scattering in isotopically mixed nanowires is unexpectedly much more significant than in bulk crystals of close isotopic compositions. This effect is explained by a nonuniform distribution of (28)Si and (30)Si isotopes in the grown isotopically mixed nanowires with local compositions ranging from x = ∼0.25 to 0.70. Moreover, we also observed that upon heating, phonons in (28)Si(x)(30)Si(1-x) nanowires behave remarkably differently from those in (29)Si nanowires suggesting a reduced thermal conductivity induced by mass disorder. Using Raman nanothermometry, we found that the thermal conductivity of isotopically mixed (28)Si(x)(30)Si(1-x) nanowires is ∼30% lower than that of isotopically pure (29)Si nanowires in agreement with theoretical predictions.

Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial.

Early evidence suggests the efficacy of voriconazole for chronic pulmonary aspergillosis (CPA). We conducted a prospective, open, multicenter trial to evaluate the efficacy and safety of voriconazole for proven CPA in minimally or non-immunocompromised patients. Patients had CPA confirmed by chest computed tomography (CT) and/or endoscopy, positive Aspergillus culture from a respiratory sample, and positive serologic test for Aspergillus precipitins. Patients received voriconazole (200 mg twice daily) for a period of 6-12 months and were followed for 6 months after the end of therapy (EOT). The primary endpoint was global success at 6 months, defined as complete or partial (≥50 % improvement) radiological response and mycological eradication. Forty-one patients with confirmed CPA were enrolled. All patients had A. fumigatus as the etiologic agent. By EOT, five patients had died from comorbidities and seven had discontinued voriconazole due to toxicity. The global success rate at 6 months was 13/41 (32 %): 10/19 (53 %) for chronic necrotizing aspergillosis and 3/22 (14 %) for chronic cavitary aspergillosis (p = 0.01). The respective success rates at EOT were 58 and 32 %. Clinical symptoms and quality of life also improved during treatment. Voriconazole is effective for CPA, with acceptable toxicity. The response rate is higher and obtained more rapidly in necrotizing than cavitary forms.

[Updated indications and contraindications in 2022 for lung transplantation in France]. / Transplantation pulmonaire en France : actualisation des indications et contre-indications en 2022.

Lung transplantation (LTx) is the last-resort treatment for end-stage respiratory insufficiency, whatever its origin, and represents a steadily expanding field of endeavor. Major developments have been impelled over the years by painstaking efforts at LTx centers to improve donor and recipient selection, and multifaceted attempts have been made to meet the challenges raised by surgical management, perioperative care, and long-term medical complications. The number of procedures has increased, leading to improved post-LTx prognosis. One consequence of these multiple developments has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. With these considerations in mind, the Francophone Pulmonology Society (Société de Pneumology de Langue Française [SPLF]) has set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force has examined the most recent literature and evaluated the risk factors that continue to limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.

[Pneumocystis jirovecii and quantitative PCR: Pneumonia or colonization?] / Pneumocytis jirovecii et PCR quantitative : pneumonie ou colonisation à Pneumocystis jirovecii ?

BACKGROUND: Quantitative PCR to detect Pneumocystis jirovecii (Pj) is a new tool for the diagnosis of Pneumocystis jirovecii pneumonia (PJP). The yield of this technique, in cases of low fungal burden, when the standard technique using immunofluorescence (IF) is negative, needs to be evaluated. METHODS: We retrospectively reviewed the charts of all patients with a positive PCR but negative IF test (PCR+/IF-) in bronchoalveolar lavage (BAL) fluid performed over one year. We used an algorithm based on underlying immunosuppression, clinical picture, thoracic CT scan appearances, existence of an alternative diagnosis and the patient's outcome on treatment. Using this, each case was classified as probable PJP, possible PJP or colonization. RESULTS: Among the 416 BAL performed, 48 (12%) were PCR+/IF- and 43 patients were analyzed. Patients were mostly male (56%) with a median age of 60 years. Thirty-five (84%) were immunocompromised: 4 (9%) HIV-infected patients, 26 (60%) with hematologic or solid organ cancer, 3 (7%) were renal transplant recipients. Seven (16%) were classified as probable PPJ and 9 (21%) as possible PJP. Patients with a probable or possible PJP were more frequently admitted to the ICU (P<0.02) and had higher risk of death (P<0.01) when compared to those with colonization. Median PCR levels were very low and were not different between PJP or colonized patients (P=0.23). CONCLUSIONS: Among patients with a positive Pj PCR in BAL but with negative IF, only 37% had probable or possible PJP and PCR could not discriminate PJP from colonization.

Clinical characteristics and prognostic factors of pulmonary MALT lymphoma.

Mucosa-associated lymphoid tissue-derived (MALT) lymphoma, a low grade B-cell extranodal lymphoma, is the most frequent subset of primary pulmonary lymphoma. Our objective was to evaluate the initial extent of disease and to analyse the characteristics and long-term outcome of these patients. All chest and pathological departments of teaching hospitals in Paris were contacted in order to identify patients with a histological diagnosis of primary pulmonary lymphoma of the MALT subtype. 63 cases were identified. The median age was 60 yrs. 36% of cases had no symptoms at diagnosis. 46% of patients had at least one extrapulmonary location of lymphoma. The estimated 5- and 10-yr overall survival rates were 90% and 72%, respectively. Only two of the nine observed deaths were related to lymphoma. Age and performance status were the only two adverse prognostic factors for survival. Extrapulmonary location of lymphoma was not a prognostic factor for overall survival or for progression-free survival. Treatment with cyclophosphamide or anthracycline was associated with shorter progression-free survival, when compared with chlorambucil. The survival data confirm the indolent nature of pulmonary MALT lymphoma. Better progression-free survival was observed with chlorambucil when compared with cyclophosphamide or anthracycline.

IFNgamma and antibody responses among French nurses during a tuberculosis contact tracing investigation.

STUDY: A comparative study which compared PPD skin testing inserted according to the French Society of Pneumology's recommendations and interferon gamma release assay (IGRA) (QuantiFERON((R)) TB Gold In-tube, QF-TB-IT, Cellestis, Carnegie, Australia) was performed during a tuberculosis contact investigation in our hospital. PATIENTS: Nineteen French health-care workers (HCWs) volunteered to participate. All of the HCW enrolled were BCG vaccinated and had a normal chest X-ray at entry. RESULTS: Among the HCW, 68.4% were TST positive. By comparison, only 31.6% had a positive QF-TB-IT result. We took advantage of the negative tube and the corresponding plasma for antibody detection by ELISA. None were ELISA positive. Fourteen HCWs were followed up. None of the HCWs accepted a course of antiTB chemoprophylaxis. Despite the difficulty in establishing a trend in kinetics, we saw the complexity of interpretation of a dynamic T-cell response after contact with an index case. CONCLUSION: This initial and first French picture provides us with the observation that only 44% of TST-positive HCW were IGRA positive, and the IGRA test allowed the detection of LTBI in two TST negative HCWs.

[Non-infectious pulmonary complications of myelodysplastic syndromes and chronic myeloproliferative disorders]. / Complications pulmonaires non infectieuses des maladies myéloprolifératives et des syndromes myélodysplasiques.

Introduction Non-infectious pulmonary complications of myelodysplasic syndromes and chronic myeloproliferative disorders are not rare but remain little known to the respiratory physician. He may be confronted with various clinical pictures corresponding to different pathophysiological causes. Background There are few data in the literature relating only to isolated cases or small series. The non infectious pulmonary complications of myelodysplasic syndromes and chronic myeloproliferative disorders can be classified into several clinical entities: tumoural syndrome, pulmonary fibrosis or diffuse infiltration, auto-immune reactions including vasculitis, Sweet's syndrome, organizing pneumonia, pulmonary alveolar proteinosis..., pleural effusion and pulmonary arterial hypertension. The diagnosis is provided by the histology and the management depends on the underlying pathology. Viewpoints and conclusion Myelodysplasic syndromes and myeloproliferative disorders are entities which are becoming better characterized and understood. Better knowledge of the pathophysiological mechanisms involved in these complications should improve their diagnosis and their management which still remains complex.

[Prospective evaluation of the efficacy of the combination of budesonide/formoterol in obstructive airway disease after allogeneic hematopoietic stem cell transplantation]. / Efficacité de l'association budésonide/formotérol dans le trouble ventilatoire obstructif survenant après allogreffe de cellules souches hématopoïétiques.

BACKGROUND: Although it has not been evaluated prospectively, the usual treatment for obstructive airway disease after allogeneic hematopoietic stem cell transplantation, which is related to graft versus host disease, consists of intensification of systemic immunosuppressive therapy. However, this treatment has a limited efficacy and is associated with a significant number of serious adverse effects, particularly infectious. Alternative treatments are therefore required. Recently, clinical and functional improvement in patients with obstructive airway disease following allogenic hematopoietic stem cell transplantation treated with inhaled combined Budesonide/Formoterol has been retrospectively reported. METHODS: The present prospective multi-centered, randomised double-blind trial is designed to evaluate the efficacy of the combination of budesonide/formoterol (400/12 microg 2 inhalations bid) versus placebo in patients with moderate to severe obstructive airway disease, not requiring initiation or intensification of systemic immunosuppressive therapy for extra thoracic graft versus host disease. The primary outcome will be the improvement of FEV1 at 1 month of treatment. The secondary outcomes will be the clinical and functional pulmonary improvements at 6 months. EXPECTED RESULTS: The leading hypothesis is that patients treated with inhaled combined Budesonide/Formoterol will show significant improvement of their clinical symptoms and pulmonary functional testing.

[The role of new antibiotics in the treatment of acute adult community acquired pneumonia]. / Place des nouveaux antibiotiques dans le traitement de la pneumonie aiguë communautaire de l'adulte.

INTRODUCTION: Several new antibiotics (ceftaroline, ceftobiprole, omadacycline, solithromycine and delafloxacin) have recently been developed. Their place in the management of community acute pneumonia (CAP) needs to be clarified. STATE OF THE ART: Because multiresistant bacteria are infrequently involved in CAP, usual regimens using third generation cephalosporins, fluoroquinolones or macrolides, alone or in combination, are effective in the overwhelming majority of cases. Several studies have highlighted the non-inferiority of the new molecules regarding their clinical efficacy compared to usual regimens. The use of these new antibiotics could reduce the treatment duration of CAP and in some cases avoid combined therapy. These antibiotics do not offer real benefits in terms of spectrum of activity compared to the current recommended treatment. The anti-toxin effect of ceftaroline and the anti-inflammatory properties of solithromycin could potentially justify their prescription over molecules currently used. CONCLUSION: Results are still pending regarding the efficacy and any possible advantages of these new molecules, and also the emergence of drug resistant bacteria. Although these drugs share some advantages, they should not be selected over antibiotics usually prescribed for the treatment of CAP.

Bacillus Calmette-Guerin infection following intravesical instillation: Does the strain matter?

PURPOSE: Intravesical BCG is the standard treatment of non-muscle invasive bladder cancer. No difference has yet been reported in the safety profiles of the various BCG strains. METHODS: A nationwide multidisciplinary retrospective survey was conducted between January 2013 and December 2016 to identify cases of BCG infection and differentiate them based on the type of BCG strain used. RESULTS: Forty patients were identified (BCG RIVM 28; other strains 8; unknown 4). Patients treated with BCG RIVM were less severely ill, with fewer occurrences of septic shock (3.6% vs. 50%, P=0.003) and ICU admission (7.1% vs. 62.5%, P=0.003). A higher frequency of pulmonary miliaries (71.4% vs. 12.5%, P=0.005) but lower transaminase levels (mean AST 65 vs. 264 U/L, P=0.001) were observed in these patients. No difference in terms of recovery was reported. CONCLUSION: The type of BCG strain could correlate with the frequency and severity of subsequent BCG infections.

Fixation neurons in the superior colliculus encode distance between current and desired gaze positions.

A visual scene is scrutinized during sequential periods of steady fixation, connected by saccades that shift the visual axis (gaze) to new positions. During such exploratory scan paths, gaze frequently strays from and then returns to salient features. How the brain keeps track of major end-goals and intermediate subgoals is not understood. We studied the discharge of fixation neurons of the brainstem's superior colliculus during multiple-step gaze shifts composed of a sequence of saccades made in the dark and separated by short periods of steady fixation. Cells were initially silent. As sequential gaze saccades approached the goal, firing began; its frequency increased progressively and peaked when gaze was on the remembered target location. We conclude that these fixation neurons encode the error between desired and actual gaze positions, irrespective of trajectory characteristics.

[Late onset, non-infectious pulmonary complications after haematological stem cell transplantation]. / Les complications pulmonaires tardives non infectieuses après allogreffe de cellules souches hématopoïétiques.

INTRODUCTION: Non infectious pulmonary complications which frequently occur in the late follow-up of haemopoietic stem cell transplant (HSCT) recipients account for an increase in mortality and morbidity. Different histological entities have been described among which bronchiolitis obliterans is the most common. BACKGROUND: Because of the absence of prospective epidemiological studies and the difficulties in obtaining surgical lung biopsies from these frail patients little is known about these conditions. Although their pathogenesis is poorly understood they probably result from a chronic pulmonary graft versus host disease (GVHD). The introduction of or increase in systemic immunosuppressive treatment, usually indicated for controlling extra-thoracic manifestations of GVHD, may lead to the resolution of an organising pneumonia but is usually ineffective in the treatment of bronchiolitis obliterans. VIEWPOINTS: Current prospective cohort studies together with randomised prospective studies evaluating more targeted treatments should help determine the frequency, the risk factors and the precise characteristics of the different entities of late non-infectious pulmonary diseases following HSCT and should also improve their management. Furthermore, the recent demonstration of lung abnormalities in animal models of chronic GVHD, similar to those observed in humans, should allow a better understanding of the pathogenesis. CONCLUSION: The prevalence of these diseases is increasing throughout the world. More precise analysis, the identification of risk factors and study of the pathophysiological mechanisms involved should allow better understanding and management than at present.

[BCG infection following intravesicular immunotherapy for bladder cancer]. / BCGites après immunothérapie pour cancer de vessie, une pathologie hétérogène: physiopathologie, description clinique, prise en charge diagnostique et thérapeutique.

BACKGROUND: Bacille of Calmette et Guérin (BCG) immunotherapy is the most effective treatment for non-muscle-invasive bladder cancer. Yet, potentially severe localized or systemic mycobacterial infections can happen. STATE OF KNOWLEDGE: In a patient who underwent BCG instillation for bladder cancer, the diagnosis of BCG infection is usually suggested by more than 3 days of high-grade fever and systemic and/or local symptoms with no other plausible alternative diagnosis. BCG infection can be localized (usually to the genitourinary tract, the bones or blood vessels) or systemic (mainly with pulmonary and hepatic involvements). The presence of granuloma in tissue biopsies (other than from the genitourinary tract) supports the diagnosis. The advent of polymerase chain reaction has recently improved the sensitivity of microbiological investigations. The management of BCG infection is not well established but relies on broad-spectrum antimycobacterial therapy (with the exclusion of pyrazinamide), glucocorticoids (in the context of general symptoms refractory to antimicrobial therapy alone) and occasionally surgery. CONCLUSION: BCG infection is a rare but not exceptional complication of BCG immunotherapy with heterogeneous clinical presentation. Prospective studies are warranted in order to improve treatment outcomes.

Reticulated platelets and uninhibited COX-1 and COX-2 decrease the antiplatelet effects of aspirin.

BACKGROUND: The mechanisms for the variability in antiplatelet effects of aspirin are unclear. Immature (reticulated) platelets may modulate the antiplatelet effects of aspirin through uninhibited cyclooxygenase (COX)-1 and COX-2. OBJECTIVES: To evaluate the role of reticulated platelets in the antiplatelet effects of aspirin. METHODS: Sixty healthy volunteers had platelet studies performed before and 24 h after a single 325-mg dose of aspirin. Platelet studies included light transmission aggregometry; P-selectin and integrin alpha(IIb)beta(3) expression, and serum thromboxane B(2) (TxB(2)) levels. Reticulated platelets and platelet COX-2 expression were measured using flow cytometry. RESULTS: Subjects were divided into tertiles based on the percentage of reticulated platelets in whole blood. Baseline platelet aggregation to 1 microg mL(-1) collagen, and postaspirin aggregations to 5 microm and 20 microm ADP and collagen, were greater in the upper than in the lower tertile of reticulated platelets. Stimulated P-selectin and integrin alpha(IIb)beta(3) expression were also higher in the upper tertile both before and after aspirin. Platelet COX-2 expression was detected in 12 +/- 7% (n = 10) of platelets in the upper tertile, and in 7 +/- 3% (n = 12) of platelets in the lower two tertiles (P = 0.03). Postaspirin serum TxB(2) levels were higher in the upper (5.5 +/- 4 ng mL(-1)) than in the lower tertile (3.2 +/- 2.5 ng mL(-1), P = 0.03), and decreased even further with ex vivo additional COX-1 and COX-2 inhibition. The incidence of aspirin resistance (>or= 70% platelet aggregation to 5 microm ADP) was significantly higher in the upper tertile (45%) than in the lower tertile (5%, P < 0.0001). CONCLUSIONS: Reticulated platelets are associated with diminished antiplatelet effects of aspirin and increased aspirin resistance, possibly because of increased reactivity, and uninhibited COX-1 and COX-2 activity.

Combined inhaled steroids and bronchodilatators in obstructive airway disease after allogeneic stem cell transplantation.

Bronchiolitis obliterans (BO) is a potentially life-threatening complication following allogeneic stem cell transplantation (SCT) and usually carries a poor prognosis. Immunosuppressive medications are the main treatment, but are rarely effective, especially when the disease is severe. Thus, both early detection and alternative therapeutic approaches of post SCT BO are needed. We report our experience with Budesonide/Formoterol, an inhaled steroid and long-acting bronchodilatator combination, in a group of patients with mild to moderately severe BO after SCT whose systemic immunosuppressive treatment had not been modified. Thirteen patients were treated. The diagnosis of BO was based on the presence of respiratory symptoms and air-trapping on expiratory lung high-resolution computed tomography in all patients, associated with irreversible airflow obstruction in seven cases. The median follow-up was 12.8 months (range: 5-29 months). All patients improved clinically, and both forced expiratory volume in 1 (FEV(1)) and mean expiratory flow values increased significantly during follow-up (534+/-268 ml in absolute values and 36+/-27% compared to pretreatment values for FEV(1); P<0.02). These encouraging results provide new insights in the therapeutic approach of BO after SCT and require confirmation in a larger group of patients with a longer follow-up.

[Respiratory infections caused by slow-growing bacteria: Nocardia, Actinomyces, Rhodococcus]. / Infections respiratoires à bactéries à croissance lente : Nocardia, Actinomyces, Rhodococcus.

INTRODUCTION: Pneumonia caused by slow-growing bacteria is rare but sometimes severe. STATE OF THE ART: These infections share many similarities such as several differential diagnoses, difficulties to identify the pathogen, the importance of involving the microbiologist in the diagnostic investigation and the need for prolonged antibiotic treatment. However, major differences distinguish them: Nocardia and Rhodococcus infect mainly immunocompromised patients while actinomycosis also concerns immunocompetent patients; the severity of nocardioses is related to their hematogenous spread while locoregional extension by contiguity makes the gravity of actinomycosis. PROSPECTIVE: For these diseases, molecular diagnostic tools are essential, either to obtain a species identification and guide treatment in the case of nocardiosis or to confirm the diagnosis from a biological sample. Treatment of these infections is complex due to: (1) the limited data in the literature; (2) the need for prolonged treatment of several months; (3) the management of toxicities and drug interactions for the treatment of Nocardia and Rhodococcus. CONCLUSION: Close cooperation between pneumonologists, infectious disease specialists and microbiologists is essential for the management of these patients.