Added value of buccal cell FISH analysis in the diagnosis and management of Turner syndrome.

STUDY QUESTION: Is there an added diagnosis value of buccal cell FISH analysis compared with blood lymphocyte chromosomal investigations in patients with Turner syndrome (TS)? SUMMARY ANSWER: Buccal cell FISH analysis, a non-invasive technique, modified the chromosomal results obtained with the blood karyotype in 17 patients (12%) of our cohort. WHAT IS KNOWN ALREADY: Few studies have evaluated buccal cell FISH analysis and compared them with blood karyotype in patients with TS. STUDY DESIGN, SIZE, DURATION: A prospective, monocentric cohort study was conducted in a rare diseases centre (CMERC) between July 2017 and August 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 142 adult patients with TS, and at least 5% 45,X cells in a previous blood karyotype, were recruited. All the patients' files were included in the CEMARA database. This national database has been declared to the French data protection agency (CNIL approval number 1187326). In compliance with French law, consent regarding non-opposition to collect and use the data was obtained from each patient. A FISH analysis on a buccal smear was performed. MAIN RESULTS AND THE ROLE OF CHANCE: The percentage of 45,X cells was identical between the two tissues in only 32.4% of cases. The discrepancy was higher than 41% for 12% of the cohort. The percentage of 45,X cells was higher in blood in 53 (37.3%) patients, and higher in buccal cells in 43 (30.3%) of cases. In 17 (12%) cases, the blood karyotype had to be reconsidered in regard to the buccal cell analysis. LIMITATIONS, REASONS FOR CAUTION: It would have been interesting to evaluate karyotypes in cells from other tissues such as cells from skin biopsy or from the urinary tract and even from blood vessels or gonads in case of surgery and to compare them with each patient's phenotype. However, most of the time, these tissues are not available. WIDER IMPLICATIONS OF THE FINDINGS: Although blood lymphocyte karyotype remains the gold standard for the diagnosis of TS, buccal cell FISH analysis is an efficient tool to evaluate the global chromosomal constitution in these patients, thus allowing them to have better care and follow-up. For instance, identifying a Y chromosome can prevent the occurrence of a gonadoblastoma, as gonadectomy should be discussed. On the other hand, finding normal XX cells in a patient with a previous diagnosis of homogenous 45,X TS, may be psychologically helpful and relevant for gynaecological care. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was sought for the study. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Infections caused by naturally AmpC-producing Enterobacteriaceae: Can we use third-generation cephalosporins? A narrative review.

The burden of antibiotic-resistant infections among Gram-negative bacteria is increasing. Resistance to third-generation cephalosporins (3GCs) in Enterobacteriaceae is mainly conferred by the acquisition of ß-lactamases or by deregulation of natural genetically-encoded ß-lactamase enzymes. Enterobacteriaceae such as Enterobacter spp., Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (ESCPM group) possess chromosomally-encoded inducible AmpC ß-lactamases. AmpC can be overproduced as a response to ß-lactam antibiotic exposure or by constitutive dysfunction of the AmpC regulation system. This overproduction can lead to the inactivation of 3GCs. Based on small clinical studies, international guidelines and expert recommendations suggest that 3GCs should be avoided as definitive therapy for infections caused by ESCPM group organisms. In this narrative review, we discuss the published literature and evaluate the risk related to 3GC use in the case of documented ESCPM infection.

[Osteochondroplastic tracheobronchopathy: About three cases]. / Trachéobronchopathie ostéochondroplastique : à propos de 3 cas.

INTRODUCTION: Osteochondroplastic tracheobronchopathy (OCTB) is a rare disorder of unknown cause that affects the tracheobronchial tree. It is characterized by multiple cartilaginous formations or bone nodules projecting into the tracheal or proximal bronchial lumen. It is usually asymptomatic because of the slow progression of the nodules. However, chronic cough, recurrent hemoptysis or recurrent respiratory infections have been reported. OBSERVATIONS: We describe the cases of three patients with symptomatic OCTB: two men and one woman consulting for bronchial infections or pneumonia with sputum difficulties (2 cases) or simply for chronic cough (1 case). In all three cases, the diagnosis was suspected because of irregularities of the tracheal or bronchial wall with calcification seen on imaging and confirmed at bronchoscopy with biopsy specimens. No specific therapy was initiated in these patients except for the treatment of associated complications or comorbidities. CONCLUSION: OCTB is a benign pathology which can lead to bronchial symptoms ranging from mild cough to severe airway obstruction due to tracheobronchial stenosis. A key to diagnosis, limiting non-essential examinations and biopsies, is to consider OCTB based on CT scan or bronchoscopy based on irregularities of the tracheal or bronchial wall with calcification.

[Benign pulmonary metastases from a leiomyoma]. / Métastases pulmonaires bénignes d'un léiomyome.

INTRODUCTION: Benign metastasizing leiomyoma (BML) is a rare cause of pulmonary nodules. They can occur in women of reproductive age who have undergone hysterectomy for uterine leiomyoma. OBSERVATION: We report the case of a 46-year-old women, who was incidentally found to have bilateral pulmonary cavitating nodules. Pathology exam was consistent with BML. CONCLUSION: Although BML is a rare cause of pulmonary nodules, it should be considered as one of the possibilities especially in young women with a history of hysterectomy for leiomyoma.

[Adverse events related to medication in hospitals from the Valencian Community. EPIDEA Study 2005-2013]. / Eventos adversos relacionados con la medicación en los hospitales de la Comunidad Valenciana. Estudio EPIDEA 2005-2013.

OBJECTIVE: To determine the prevalence of Adverse Events related to Medication (AEM) in hospitals of the Valencian Community in the 2005-2013 study period, and to describe the associated risk factors and their impact. METHODS: This study is based on data and methodology of the Study of Prevalence of Adverse Events in hospitals (EPIDEA), since its inception in 2005 until 2013. AEM produced in each year were analyzed. RESULTS: We identified 344 AEM that occurred in 337 patients, among 35,103 patients studied, giving a prevalence of patients with AEM of 0.96% (IC95% 0.89-1.07). The most prevalent intrinsic risk factors for AEM were hypertension, diabetes and cancer. The most prevalent extrinsic risk factors were peripheral venous catheter, urinary catheter and central venous catheter. Therapeutic groups most frequently involved were systemic antibiotics, cardiovascular drugs and antineoplastics. The 61.17% of AEM was classified as moderate, followed by 27.18% as mild and 11.65% as severe. The 33.99% of EAM caused increase of the patient's stay and 39.90% of EAM caused the re-entry of patient. The 58.5% of AEM were avoidable. Mild AEM were avoidable in 46.3%, moderate AEM were avoidable in 60.3% and severe AEM were in 75% (p = 0.013). CONCLUSIONS: The prevalence of patients with AEM in hospitals of the Community of Valencia for the period 2005- 2013 was 0.96%. More than half of AEM were preventable, and preventability increases significantly with the severity of the event.

Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de pneumologie de langue française (summary).

Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.

Clinical validation of a prognostic tool in a population of outpatients treated for incurable cancer undergoing anticancer therapy: PRONOPALL study.

BACKGROUND: In 2008, a study of the characteristics of hospitalised patients led to the development of a prognostic tool that distinguished three populations with significantly different 2-month survival rates. The goal of our study aimed at validating prospectively this prognostic tool in outpatients treated for cancer in terminal stage, based on four factors: performance status (ECOG) (PS), number of metastatic sites, serum albumin and lactate dehydrogenase. PATIENTS AND METHODS: PRONOPALL is a multicentre study of current care. About 302 adult patients who met one or more of the following criteria: life expectancy under 6 months, performance status ≥ 2 and disease progression during the previous chemotherapy regimen were included across 16 institutions between October 2009 and October 2010. Afterwards, in order to validate the prognostic tool, the score was ciphered and correlated to patient survival. RESULTS: Totally 262 patients (87%) were evaluable (27 patients excluded and 13 unknown score). Median age was 66 years [37-88], and women accounted for 59%. ECOG PS 0-1 (46%), PS 2 (37%) and PS 3-4 (17%). The primary tumours were: breast (29%), colorectal (28%), lung (13%), pancreas (12%), ovary (11%) and other (8%). About 32% of patients presented one metastatic site, 35% had two and 31% had more than two. The median lactate dehydrogenase level was 398 IU/l [118-4314]; median serum albumin was 35 g/l [13-54]. According to the PRONOPALL prognostic tool, the 2-month survival rate was 92% and the median survival rate was 301 days [209-348] for the 130 patients in population C, 66% and 79 days [71-114] for the 111 patients in population B, and 24% and 35 days for [14-56] the 21 patients in population A. These three populations survival were statistically different (P <0.0001). CONCLUSION: PRONOPALL study confirms the three prognostic profiles defined by the combination of four factors. This PRONOPALL score is a useful decision-making tool in daily practice.

Effectiveness of a programme to reduce the burden of catheter-related bloodstream infections in a tertiary hospital.

The objective of this study was to assess the effectiveness of a catheter-related bloodstream infection (CR BSI) reduction programme and healthcare workers' compliance with recommendations. A 3-year surveillance programme of CR BSIs in all hospital settings was implemented. As part of the programme, there was a direct observation of insertion and maintenance of central venous catheters (CVCs) to determine performance. A total of 38 education courses were held over the study period and feedback reports with the results of surveillance and recommendations were delivered to healthcare workers every 6 months. A total of 6722 short-term CVCs were inserted in 4982 patients for 58 763 catheter-days. Improvements of compliance with hand hygiene was verified at the insertion (87·1-100%, P < 0·001) and maintenance (51·1-72·1%, P = 0·029) of CVCs; and the use of chlorhexidine for skin disinfection was implemented at insertion (35·7-65·4%, P < 0·001) and maintenance (33·3-45·9%, P < 0·197) of CVCs. There were 266 CR BSI incidents recorded with an annual incidence density of 5·75/1000 catheter-days in the first year, 4·38 in the second year [rate ratio (RR) 0·76, 95% confidence interval (CI) 0·57-1·01] and 3·46 in the third year (RR 0·60, 95% CI 0·44-0·81). The education programme clearly improved compliance with recommendations for CVC handling, and was effective in reducing the burden of CR BSIs.

[Comorbidities of COPD]. / Les comorbidités dans la BPCO.

COPD is a slowly progressive chronic respiratory disease causing an irreversible decrease in air flow. The main cause is smoking, which provokes inflammatory phenomena in the respiratory tract. COPD is a serious public health issue, causing high morbidity, mortality and disability. Related comorbidities are linked to ageing, common risk factors and genetic predispositions. A combination of comorbidities increases healthcare costs. For instance, patients with more than two comorbidities represent a quarter of all COPD sufferers but account for half the related health costs. Our review describes different comorbidities and their impact on the COPD prognosis. The comorbidities include: cardiovascular diseases, osteoporosis, denutrition, obesity, ageing, anemia, sleeping disorders, diabetes, metabolic syndrome, anxiety-depression and lung cancer. The prognosis worsens with one or more comorbidities. Clinicians are faced with the challenge of finding practical and appropriate ways of treating these comorbidities, and there is increasing interest in developing a global, multidisciplinary approach to management. Managing this chronic disease should be based on a holistic, patient-centred approach and smoking cessation remains the key factor in the care of COPD patients.

Catheter-related bloodstream infection: burden of disease in a tertiary hospital.

BACKGROUND: Surveillance programmes have become the most effective tool for controlling catheter-related bloodstream infections (CRBSI). However, few studies have investigated programmes covering all hospital settings. AIM: To describe the results of a control and prevention programme for CRBSI based on compliance with recommendations for insertion and maintenance, using annual burden of disease in a tertiary level hospital. METHODS: A CRBSI control and prevention programme involving all hospital settings was implemented. The programme consisted of CRBSI surveillance, direct observation of insertion and maintenance of catheters to determine performance, and education for healthcare workers. FINDINGS: In total, 2043 short-term catheters were inserted in 1546 patients for 18,570 catheter-days, and 279 long-term catheters were inserted in 243 patients for 40,440 catheter-days. The annual incidence density was 5.98 (first semester 6.40, second semester 5.64) CRBSI per 1000 catheter-days for short-term catheters, and 0.57 (first semester 0.66, second semester 0.43) CRBSI per 1000 catheter-days for long-term catheters. One hundred and forty insertion procedures were observed, with an average insertion time of 13 (standard deviation 7) min. Compliance with recommendations was as follows: hand hygiene, 86.8%; use of alcoholic chlorhexidine solution for skin disinfection, 35.5%; use of mask, 93.4%; use of gloves, 98.7%; use of gown, 75.0%; use of sterile cloth, 93.8%; use of cap, 92.2%; bandage application, 62.7%; and use of aseptic technique, 89.5%. Forty-five maintenance procedures were observed, and compliance rates were as follows: hand hygiene, 42.1%; use of gloves, 78.1%; and port disinfection with alcoholic chlorhexidine solution, 32.5%. CONCLUSION: The CRBSI control and prevention programme implemented at the study hospital has decreased the rate of CRBSI, provided important information about the total burden of disease, and revealed possible ways to improve interventions in the future.

[Treatment of distal airways involvement in COPD]. / Prise en charge thérapeutique de l'atteinte des voies aériennes distales dans la BPCO.

INTRODUCTION: The current pharmacological treatment of COPD provides only partial beneficial effects on symptoms, exercise tolerance, frequency of exacerbations and quality of life. This could be related to poor targeting of the distal airways by current treatments, yet these airways are particularly involved in airflow obstruction and its consequences such as hyperinflation. BACKGROUND: Many treatments used in COPD could have effects on distal airways, including bronchodilators, corticosteroids, mucolytics and antibiotics. However, these possible effects remain poorly understood. VIEWPOINTS: New treatments targeting more specifically the mechanisms of inflammation, oxidative stress and tissue remodeling that characterize COPD, could prove useful in its management, but most are still only in the early stages of their development. Advances could also come from improvements in inhalation devices, delivering more of the medication to the distal airways. CONCLUSIONS: Improvement in the management of COPD could come from progress in terms of both molecules and their mode of administration.

Update on the roles of distal airways in COPD.

This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD), which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure), were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils), dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life) and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.

A bridge from bioimpedance spectroscopy to 50 kHz bioimpedance analysis: application to total body water measurements.

This paper presents a method for extrapolating the total body water (TBW) resistance R(t50) from the resistance measured at 50 kHz (R(50)). A DXA examination and impedance measurements were carried out in a 1st group of 57 healthy volunteers with a Xitron 4200 multifrequency impedancemeter, in order to determine their values of R(t50) by comparison with resistances extrapolated at an infinite frequency by the Xitron (R(infinity)). TBW volumes were calculated using our modified BIS method (Jaffrin et al 2006 Med. Biol. Eng. Comput. 44 873-82) from R(infinity), R(t50) and from the fat-free mass measured by DXA, assuming a hydration rate of 73.2%. The same protocol and calculations were also carried out on a 2nd group of 21 subjects for independent validation. Data of the 1st group showed that values of R(t50), not significantly different from those of R(infinity), could be obtained by dividing R(50) by 1.231 in men and by 1.224 in women. Applying this method to the 2nd group yielded also values of R(t50) not significantly different from R(infinity). TBW volumes V(t50) obtained from R(t50) were not significantly different from those of our modified BIS method V(tn), or from TBW volumes obtained from DXA in both groups. A comparison with three BIA methods of TBW determination showed that our new method gave results in better agreement with TBW from DXA and from our modified BIS method.

[Invasion of the pulmonary artery by an undifferentiated carcinoma]. / Obstruction tumorale de l'artère pulmonaire par un carcinome indifférencié

INTRODUCTION: The diagnosis of chronic obstruction of the pulmonary artery is difficult. We present the case of a woman with an invasive, undifferentiated carcinoma of the pulmonary artery. CASE REPORT: A 61 year old woman complained of increasing dyspnoea. This was evaluated by computed tomography which showed a defect in the main pulmonary artery. There was no clinical or radiological improvement following anticoagulant treatment for two months. A repeat CT scan showed a persisting intravascular defect and the diagnoses considered included post-embolic pulmonary arterial hypertension and angiosarcoma. A surgical biopsy was performed and pericardial and aortic tumour nodules were found during the operation. The pathological examination revealed undifferentiated carcinoma. Further investigations failed to reveal the primary site. CONCLUSION: Invasion of the pulmonary artery by angiosarcoma or other tumour is part of the differential diagnosis of chronic thromboembolic disease. The diagnosis rests on histology obtained by an intravascular or surgical procedure. Complete surgical excision may be possible in angiosarcoma but it was impossible in our patient. The patient died despite two courses of chemotherapy and targeted therapy with erlotinib.

[Miliary induced by intravesical BCG immunotherapy for carcinoma of the bladder: CT Findings]. / Miliaire pulmonaire secondaire à une immunothérapie intravésicale par le Bacille de Calmette-Guérin: aspect TDM.

The authors describe the case of a patient presenting miliary involvement of the lung due to mycobacterium bovis after intravesical BCG administration. After initial transurethral resection, the patient was treated with immunotherapy by intravesical instillation of BCG and received 9 treatments without any problem. After the 10th treatment, the patient presented with cough and signs of urinary infection. At admission the chest radiograph showed a miliary pattern, better seen at high resolution CT, and using helical technique with the maximum intensity projection (MIP) reconstructions. MIP demonstrated to better advantage the well defined contours of the nodules, distributed evenly and randomly in the whole lung. After anti-TB treatment, the patient had regained full activity with persistence of the miliary pattern but a decreased number and size of nodules and calcification in some of them. This case illustrates a rare complication of intravesical immunotherapy, and points out the superiority of Sliding Thin Slab MIP (STS-MIP) compared with standard HRCT which allows a better detection of extent and follow-up of a military pattern, notably in moderate forms, by improvement of the anatomical resolution.