Impacto de la evaluación pulmonar ecográfica durante un lavado pulmonar total: caso pediátrico de proteinosis alveolar pulmonar / The impact of lung ultrasound assessment during a whole lung lavage: a paediatric case of pulmonary alveolar proteinosis

El lavado pulmonar total (LPT) es la principal terapia para la proteinosis alveolar pulmonar (PAP). Formulamos la hipótesis de la aplicabilidad de la ecografía pulmonar (EP) para guiar el alcance de la inundación alveolar en un varón de 15 años. El LPT de cada pulmón consistió en la instilación de solución salina, seguida de quinesioterapia y drenaje de líquidos. En el primer LPT, el proceso se repitió hasta observar el aclaramiento macroscópico progresivo del líquido de lavado, con visualización simultánea de las fases de aireación pulmonar mediante EP. En la segunda etapa, se utilizó un patrón de EP para guiar la extensión del lavado. La aparición del patrón de tipo tisular mediante broncograma del fluido definió la terminación temprana de la infusión salina. En conclusión, la EP contribuyó a monitorizar las fases de la desaireación pulmonar a lo largo del LPT, y redujo la cantidad total de solución salina instilada, con el fin de minimizar sus complicaciones inherentes.(AU)

Whole lung lavage (WLL) is the first-line treatment for pulmonary alveolar proteinosis. We hypothesized that lung ultrasound (LUS) would guide flooding during treatment in a 15-year-old boy. WLL of each lung consisted of instillation of saline followed by kinesiotherapy and fluid drainage. In the first WLL, the lung was repeatedly flooded until the lavage fluid was clear on macroscopic examination. During this process, LUS was used to visualise lung aeration. In the second WLL, we used LUS signs to guide the lavage volume. The appearance of the fluid bronchogram sign showed that saline infusion could be stopped earlier than in the first lavage. In conclusion, LUS helped monitor the different stages of controlled lung de-aeration during WLL and reduce the total amount of saline used. This technique will also reduce the risk of WLL-related complications.(AU)

The impact of lung ultrasound assessment during a whole lung lavage: A paediatric case of pulmonary alveolar proteinosis.

Whole lung lavage (WLL) is the first-line treatment for pulmonary alveolar proteinosis. We hypothesized that lung ultrasound (LUS) would guide flooding during treatment in a 15-year-old boy. WLL of each lung consisted of instillation of saline followed by kinesiotherapy and fluid drainage. In the first WLL, the lung was repeatedly flooded until the lavage fluid was clear on macroscopic examination. During this process, LUS was used to visualise lung aeration. In the second WLL, we used LUS signs to guide the lavage volume. The appearance of the fluid bronchogram sign showed that saline infusion could be stopped earlier than in the first lavage. In conclusion, LUS helped monitor the different stages of controlled lung de-aeration during WLL and reduce the total amount of saline used. This technique will also reduce the risk of WLL-related complications.

The year's new drugs and biologics 2019.

Highlights of our annual review of new approvals and launches on global drug markets include the approval and launch of Trikafta, the most widely applicable treatment to date for cystic fibrosis; approval of the first Ebola vaccine for general (rather than emergency) use; the pilot rollout in three African countries of the world's first malaria vaccine; approval of a new treatment option for multidrug-resistant bacterial infections; and the approval and launch in China of the first new drug to treat Alzheimer's disease in more than a decade. Several new immune checkpoint inhibitors and antibody-drug conjugates were approved for cancer indications, confirming continued industry enthusiasm for cancer immunotherapy. The most notable trend of 2019 was the granting by the Food and Drug Administration (FDA) of a record number of accelerated approvals, many of which were issued several months ahead of the expected action date.

The year's new drugs and biologics 2018: Part II - News that shaped the industry in 2018.

This eagle's-eye overview of the drug industry in 2018 provides insight into some of last year's top stories, including a large and still growing outbreak of Ebola in the Democratic Republic of the Congo, as well as the potential uses (and abuses) of CRISPR technology. As in previous years, we also review orphan drug development, new regulatory agency-supported programs such as Priority Medicines Scheme (PRIME) and Sakigake, pipeline attrition, and pharma/biotech mergers and acquisitions of note. Finally, we take a glimpse into the crystal ball to anticipate the new drugs that will be approved in 2019.

The year's new drugs and biologics 2018: Part I.

Sixty-four new drugs and biologics reached their first global markets in 2018, the greatest number in at least a decade. In addition, 19 important new line extensions (new indications, new combinations or new formulations of previously marketed drugs) were introduced over the course of 2018. Twenty-three other new products and new line extensions were approved but not launched before December 31. As has been the trend in recent years, oncology was the most active therapeutic area in terms of new launches, with cancer drugs accounting for 25% of all novel drugs and biologics introduced worldwide last year. Eight first-in-class agents were launched for the first time in 2018, including the first RNA interference agent as well as the photo-finish approval and rollout of the first three members of a radically different class of non-vasoconstricting antimigraine agents, the anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies. Twenty-nine of the drugs launched last year were designated orphan drugs, reflecting the continued upswing in investment in the area of neglected diseases. This is especially true in the U.S., which welcomed 25 of the newly launched orphan drugs. Overall, the U.S. was the most active market for new drugs and biologics, accounting for two-thirds of all new launches in 2018.

The year's new drugs & biologics, 2017, part II - News that shaped the industry in 2017.

This eagle's-eye overview of the drug industry in 2017 provides insight into some of last year's top stories, including the growing opioid crisis affecting the U.S. and other developed countries and the 2017-2018 influenza epidemic, with a spotlight on the need for a universal flu vaccine. As in previous years, we also review orphan drug development, new agency-supported programs such as PRIME and RMAT, pipeline attrition and drug pricing, as well as pharma/biotech mergers and acquisitions of note. Finally, we take a glimpse into the crystal ball to anticipate the new drugs that will be approved in 2018.

The year's new drugs and biologics 2017: Part I.

This review presents the 113 new drugs and biologics that were approved or launched for the first time globally in 2017. Fifty-two new drugs and biologics reached their first markets worldwide in 2017. Seven of the new launches were first-in-class agents, meaning the first drug with a novel mechanism of action to be approved and launched anywhere in the world. In addition, 36 notable line extensions (i.e., new indications, new combinations and new formulations of previously marketed products) were introduced last year. The remaining 25 products discussed in this article were approved for the first time during the year just passed, but had not yet been launched as of December 31, 2017. The United States was the most active market for new drugs, and oncology was the most active therapeutic group. Information on these new arrivals is covered in depth in part I of our annual review of the pharma and biotech industry.

The year's new drugs & biologics 2016: Part I.

Nearly 90 new drugs and biologics, including important new line extensions, were approved or launched for the first time globally in 2016, a comparatively lower number with respect to previous years. Forty-four new drugs and biologics reached their first markets worldwide in 2016, nearly 10% fewer than the previous year. Seven of the new launches were first-in-class agents, meaning the first drug with a novel mechanism of action to be approved and launched anywhere in the world. In addition, 23 novel line extensions (i.e., new formulations, new combinations and new indications) were introduced last year. The remaining 21 products discussed in this article were approved for the first time during the year just passed, but had not yet been launched as of December 15, 2016. Information on these new arrivals is covered in depth in part I of our annual review of the pharma and biotech industry.

Association between sleep stages and hunger scores in 36 children.

BACKGROUND: Childhood obesity is a growing health challenge. Recent studies show that children with late bedtime and late awakening are more obese independent of total sleep time. In adolescents and adults, a delayed sleep phase has been associated with higher caloric intake. Furthermore, an adult study showed a positive correlation between REM sleep and energy balance. This relationship has not been demonstrated in children. However, it may be important as a delayed sleep phase would increase the proportion of REM sleep. OBJECTIVES: This study investigated the relationship between hunger score and sleep physiology in a paediatric population. METHODS: Thirty-six patients referred for a polysomnogram for suspected obstructive sleep apnoea were enrolled in the study. Sleep stages were recorded as part of the polysomnogram. Hunger scores were obtained using a visual analogue scale. Mean age was 9.6 ± 3.5 years. RESULTS: Mean hunger scores were 2.07 ± 2.78. Hunger scores were positively correlated with percentage of total rapid eye movement (REM) sleep (r = 0.438, P < 0.01) and REM sleep duration in minutes (r = 0.471, P < 0.05). Percentage slow wave sleep (SWS) was negatively correlated with hunger score (r = -0.360, P < 0.05). There were no correlations between age, sex, body mass index percentiles, apnoea-hypopnoea index, total sleep time, sleep efficiency, sleep onset latency, stage 2 sleep duration and hunger scores. CONCLUSIONS: These findings suggest that delayed bedtime, which increases the proportion of REM sleep and decreases the proportion of SWS, results in higher hunger levels in children.

[Acceptance of influenza vaccination by caregivers in a geriatric and long-term care institution]. / Acceptation de la vaccination antigrippale par les soignants au sein d'une institution gériatrique et médicosociale.

INTRODUCTION: Seasonal influenza is a viral transmissible infectious disease causing increased morbidity or mortality in frail subjects, especially those living in institutions. Measures to prevent the impact of infectious diseases were proposed based on the use of influenza vaccination among health-care professionals. We wanted to evaluate the acceptance of our institutional vaccination procedure initiated in 2005 and possible improvement. METHODS: A questionnaire was sent in May 2007 to all health-care professionals (n=730) to identify their current vaccine status in 2006 and their opinion concerning vaccination against influenza in 2007. RESULTS: Subsequently, 369 (50.2%) responses were obtained. Amongst those responding, 31.7% were vaccinated in 2006, 77.8% using the institutional procedure. Also, 221 (87.7%) nonvaccinated health-care professionals indicated their position concerning influenza vaccination: 37% of them would accept the vaccination in 2007 (on the condition that our current institutional procedure be improved), 63% of them would refuse influenza vaccines in spite of any improvement. CONCLUSION: Our study emphasizes that the use of an adapted procedure for influenza vaccination among health-care professionals could improve vaccine coverage. It also emphasizes that a margin of those professionals are still reluctant to vaccination.

[Epidemiology of candidemia: results of a one month French hospitals-based surveillance study in 2004]. / Epidémiologie des fongémies dans les hôpitaux français non universitaires en 2004: enquête multicentrique ColBVH.

INTRODUCTION: The aim of our study was to determinate the frequency of candidemia, the species encountered and their susceptibility to antifungal agents in French hospitals in 2004. METHODS: A prospective survey of septicaemia, including candidaemia was conducted among 193 non teaching French hospitals during October 2004. All bloodstream infections were reported and the bloodstream isolates sent to two coordinating centers. Species identification and susceptibility were performed by biologists as usual, and further confirmed by use of alternative methods, including Minimal Inhibitory Concentration (MIC) determination. RESULTS: The survey was effective in 93 hospitals, where 2013 bloodstream infections were noticed, including 46 candidaemia (2.3%). Candida sp. Is the 7th pathogen responsible for bloodstream infection, without concern of the origin of the infection. Candidaemia was hospital acquired in 80.4% of cases (N=37/46). Candidaemia represents 0.7% (N=9/1211) of community-acquired bloodstream infections but 4.5% (N=37/802) of nosocomial cases, placing Candida sp. at the 5th row of frequency in this last group. No mistakes were noticed during identification, but two strains were not named. After confirmation of identification, species are distributed as follows: 23 C.albicans (50%), 13 C.glabrata (28.3%), 5 C.tropicalis (10.9%), 3 C.parapsilosis (6.5%), 1 C.krusei (2.2%), and 1 C.kefyr (2.2%). The overall susceptibility is 97.7% for amphotericin B, 93.2% for 5-fluorocytosin, 88.6% for fluconazole, 70.5% for itraconazole, 95.5% for voriconzole and 100% of strains had very low MIC for caspofungin. Concerning the two main species isolated, 95.5% of C.albicans strains remain susceptible to fluconazole, but only 69% of C.glabrata strains. Two strains, 1 C.albicans and 1 C.glabrata exhibit cross resistance to azoles. The majority of amphotericin, fluconazole, and itraconazole decreased susceptibility strains are found into C.glabrata strains, but susceptibility to 5-fluorocytosin and very low MCI to caspofungin remained in this species. CONCLUSION: Our survey allowed us to get data from French non-teaching hospitals in 2004 about frequency of candidaemia among septicaemia. Candida species distribution and in vitro susceptibility patterns of the strains isolated. Candidaemia is not a rare event, specially when septicaemia is nosocomially acquired. C.albicans is the main species isolated and remains highly in vitro susceptible to antifungals. One important feature is the frequency of C.glabrata in our survey. Considering its decreased susceptibility to azoles, this finding confirms the need for rapid identification of yeast isolated from bloodstream samples, and antifungal susceptibility testing each time it is available.

A subgroup of HOX Abd-B gene is differentially expressed in cervical cancer.

The HOX genes are a family of transcription factors that bind to specific sequences of DNA in target genes regulating their expression. The role of HOX genes in adult cell differentiation is still obscure, but growing evidence suggests that they may play an important role in the development of cancer. In order to study the role of the HOX Abd-B genes in cervical cancer, we analyzed their expression in cervical tissues. Reverse transcription-polymerase chain reaction and RNA in situ hybridization were used to detect HOX Abd-B messenger RNA expression in nine normal cervical tissues and ten cervical carcinomas. The normal tissues were human papillomavirus (HPV) negative, whereas all invasive carcinomas included were HPV16 positive. In this study, we show that HOXA9, A10, A11, A13, B9, D11, and D13 genes are expressed in both the epithelium of normal tissues and neoplastic cells from squamous cervical carcinomas. Interestingly, the HOXC10 and D12 genes were not expressed in any cervical tissues; however, HOXB13, C9, C11, C12, C13, D9, and D10 genes were expressed only in the tumoral tissues but not in the normal cervix. Our findings suggest that the expression of HOXB13, D9, D10, and HOXC cluster (HOXC9, C11-C13) genes might be an important step involved in cervical cancer.

HOXB homeobox gene expression in cervical carcinoma.

The homeobox (HOX) genes are a family of transcription factors that bind to specific DNA sequences in target genes regulating gene expression. Thirty-nine HOX genes have been mapped in four conserved clusters: A, B, C, and D; they act as master genes regulating the identity of body segments along the anteroposterior axis of the embryo. The role played by HOX genes in adult cell differentiation is unclear to date, but growing evidence suggests that they may play an important role in the development of cancer. To study the role played by HOX genes in cervical cancer, in the present work, we analyzed the expression of HOXB genes and the localization of their transcripts in human cervical tissues. Reverse transcription-polymerase chain reaction analysis and nonradioactive RNA in situ hybridization were used to detect HOXB expression in 11 normal cervical tissues and 17 cervical carcinomas. It was determined that HOXB1, B3, B5, B6, B7, B8, and B9 genes are expressed in normal adult cervical epithelium and squamous cervical carcinomas. Interestingly, HOXB2, HOXB4, and HOXB13 gene expression was found only in tumor tissues. Our findings suggest that the new expression of HOXB2, HOXB4, and B13 genes is involved in cervical cancer.

[Surveillance of antimicrobial resistance of bacteria isolated from bloodstream infections: data of the French National Observatory for Epidemiology of Bacterial Resistance to Antibiotics (ONERBA), 1998-2003]. / Surveillance de la résistance bactérienne aux antibiotiques dans les bactériémies: données de l'observatoire national de l'épidémiologie de la résistance bactérienne aux antibiotiques (ONERBA) 1998-2003.

UNLABELLED: The French national observatory for epidemiology of bacterial resistance to antibiotics (ONERBA) includes numerous networks for the surveillance of bacterial resistance to antibiotics. OBJECTIVE: The aim of this study was to update antimicrobial resistance data of bacterial pathogens isolated from blood cultures. METHOD: Data was collected from several surveillance surveys reviewed by the ONERBA scientific committee during 2003. RESULTS: Gram positive cocci and Gram negative bacilli accounted respectively for 45 and 49% of all bacteria isolated from blood cultures (N=19 882). The frequency of MRSA among S. aureus was 35%. The frequencies of resistance to penicillin, amoxicillin and cefotaxime of S. pneumoniae were 10, 2, and 0.2%, respectively. In 2002, 70% of coagulase negative staphylococci were resistant to methicillin. Only 50 and 60% of E. coli isolates were susceptible to aminopenicillin and a combination amoxicillin-clavulanic acid, respectively. Since 2001, the susceptibility of E. coli isolates to ciprofloxacin has been regularly decreasing. Imipenem and ceftazidime were the most active antimicrobial agents against P. aeruginosa with a susceptibility rates below 90%. CONCLUSION: Data provided by the ONERBA should allow to improve the quality of empiric antimicrobial treatments.

Comparative in vitro activity of faropenem and 11 other antimicrobial agents against 250 invasive Streptococcus pneumoniae isolates from France.

The aim of the study presented here was to evaluate the in vitro activity of faropenem, a new member of the penem class intended for oral administration, compared with 11 other antimicrobial agents against a large number of Streptococcus pneumoniae strains isolated from adults and children with bloodstream infections in France. The minimum inhibitory concentration of faropenem against 90% of the pediatric strains tested was generally one to two dilutions lower than the most potent beta-lactam agents (i.e., 0.5 micro g/ml for faropenem vs. 1 for amoxicillin, 1 for cefotaxime and 0.5 micro g/ml for ceftriaxone). Against the adult strains, only moxifloxacin had a MIC(90) value similar to faropenem (i.e., 0.25 micro g/ml for both agents). Faropenem seems to be a promising antimicrobial agent for the treatment of adult and pediatric Streptococcus pneumoniae infections.

Frequency of isolation and antimicrobial susceptibility of bacterial pathogens isolated from patients with bloodstream infections: a French prospective national survey.

All bloodstream strains, total 1463, isolated during a 1 month period in 105 hospitals representing all geographical areas in France were collected to study their antimicrobial susceptibility. The three major species were Escherichia coli, Staphylococcus aureus and coagulase-negative staphylococci. Among the 242 S. aureus, 87 were resistant to methicillin and among those 99% were resistant to ciprofloxacin, 11.5% to gentamicin, 1% to quinupristin/dalfopristin and 8% were heterogeneously resistant to vancomycin. Study of the methicillin-resistant S. aureus indicated that 12 clones had disseminated in French hospitals, six being heterogeneously resistant to vancomycin. Among the Streptococcus pneumoniae, 43% showed decreased susceptibility to the penicillins and 42% to erythromycin. One isolate was highly resistant to fluoroquinolones. Gentamicin, cefotaxime, ciprofloxacin and gatifloxacin resistance was rare in Enterobacteriaceae with 95% of strains susceptible. The incidence of extended-spectrum beta-lactamases was quite low. Moreover more than 25% of Pseudomonas aeruginosa strains were resistant to ciprofloxacin and gentamicin. The magnitude of antibiotic resistance in bloodstream isolates, in particular Gram-positive bacteria, emphasizes the importance of hospital control measures, rational prescribing policies and new vaccine strategies.

A simple method for the construction of small format tissue arrays.

Tissue arrays can evaluate molecular targets in high numbers of samples in parallel. Array construction presents technical difficulties and tissue arrayers are expensive, particularly for small and medium sized laboratories. This report describes a method for the construction of 36 sample arrays using widely available materials. A blunted 16 gauge needle for bone marrow aspiration was used to extract paraffin wax cylinders and manually define a 6 x 6 matrix on a blank paraffin wax block. Tissue cores from 36 paraffin wax embedded premalignant lesions and invasive cervical carcinomas were injected into the matrix using a 14 gauge needle. This tissue array was sectioned using a standard microtome and used for the immunodetection of CD44 variant 9 and interleukin 18 with satisfactory results. This method can be applied in any laboratory, without the need of specialised equipment, offering a good alternative for the wider application of tissue arrays.