Louis-Ferdinand Destouches’ Medical Writing: an Apologia for Industrial and Social Modernization

This article proposes an analysis of the medical writings of Louis-Ferdinand Destouches. These writings reveal a critical reflection, in no way a whitewash, on hygiene and public health problems imposed by the war of 14–18. These medical writings, immediate post-war products, show thinking which is in line with the social and ideological ideas we find in Semmelweis, the first of the texts collected in Celine Book 3 (The Basedowine closes collection). Contemporary with the debates of the 20s, he questioned medical theses dedicated to the glorification of industrial and social modernization. Here is presented and clarified some data on their acceptance by the medical profession, the development of Destouches’ career, and his vision of his profession, concluding that these medical writings can be considered embryonic of the views of the man who would become Louis-Ferdinand Céline. Written, mostly, on behalf of the League of Nations during the period 1924–1932, these medical writings, like his medical history, provide the main leitmotifs that will illustrate the Celinian universe: miserable conditions, poverty, alcoholism and human degradation, all the things that made it difficult to exercise the profession of doctor in the urban-industrial society of the early twentieth century. Medicine was my calling (…) Since I was a child I have dreamed of becoming a doctor, I dreamed of healing people (…) (Céline, 1961, p. 207)info:eu-repo/semantics/publishedVersio

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe

Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

Background: Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. Methods: A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. Results: Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. Conclusion: aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe

Development and validation of a rabbit model of Pseudomonas aeruginosa non-ventilated pneumonia for preclinical drug development

BackgroundNew drugs targeting antimicrobial resistant pathogens, including Pseudomonas aeruginosa, have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections.MethodsWe report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with Pseudomonas aeruginosa by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression.ResultsIn a rabbit model of non-ventilated pneumonia, endobronchial challenge with live P. aeruginosa strain 6206, but not with UV-killed Pa6206, caused acute respiratory distress syndrome, as evidenced by acute lung inflammation, pulmonary edema, hemorrhage, severe hypoxemia, hyperlactatemia, neutropenia, thrombocytopenia, and hypoglycemia, which preceded respiratory failure and death. Pa6206 increased >100-fold in the lungs and then disseminated from there to infect distal organs, including spleen and kidneys. At 5 h post-infection, 67% of Pa6206-challenged rabbits had PaO2 <60 mmHg, corresponding to a clinical cut-off when oxygen therapy would be required. When administered at 5 h post-infection, humanized dosing regimens of tobramycin and meropenem reduced mortality to 17-33%, compared to 100% for saline-treated rabbits (P<0.001 by log-rank tests). For meropenem which exhibits time-dependent bactericidal activity, rabbits treated with a humanized meropenem dosing regimen of 80 mg/kg q2h for 24 h achieved 100% T>MIC, resulting in 75% microbiological clearance rate of Pa6206 from the lungs. For tobramycin which exhibits concentration-dependent killing, rabbits treated with a humanized tobramycin dosing regimen of 8 mg/kg q8h for 24 h achieved Cmax/MIC of 9.8 ± 1.4 at 60 min post-dose, resulting in 50% lung microbiological clearance rate. In contrast, rabbits treated with a single tobramycin dose of 2.5 mg/kg had Cmax/MIC of 7.8 ± 0.8 and 8% (1/12) microbiological clearance rate, indicating that this rabbit model can detect dose-response effects.ConclusionThe rabbit model may be used to help predict clinical efficacy of new antibacterial drugs for the treatment of non-ventilated P. aeruginosa pneumonia

HER-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival

The original publication is available at the Annals website at www.springerlink.com/content/1534-4681.Background: HER-2/neu (c-erbB-2, HER2) gene amplification and protein overexpression have been associated with poor prognosis in several solid tumors, including breast and gastric cancer. Its incidence and significance in esophageal adenocarcinoma is unknown. Materials and Methods: Tissue microarrays were successfully constructed from 89 paraffin-embedded archival specimens of esophageal adenocarcinomas for HER2 gene amplification by silver-enhanced in situ hybridization (SISH). No patients had undergone neoadjuvant therapy. Protein overexpression was tested with immunohistochemistry (IHC) using automated immunostaining (Ventana Benchmark). Incidence of HER2 positivity, correlation to clinicopathological variables in esophageal cancer patients, and concordance between SISH and IHC were determined. Results: True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression. No significant associations were found among gene amplification and clinicopathological factors. The 5-year survival rates were 57% for esophageal cancer patients with HER2 amplification compared with 32% without, but the difference in overall survival was not significant (P = .37). The correlation between SISH and IHC was statistically significant (P < .0001). Conclusion: While molecular targeting may be possible for approximately 16% of esophageal adenocarcinoma patients, HER2 oncogene amplification did not influence survival in this study.Sarah K. Thompson, Thomas R. Sullivan, Ruth Davies and Andrew R. Ruszkiewic

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic The past and the near future

BackgroundThis study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases.Materials and methodsA survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019.ResultsQuestionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples.ConclusionsThe COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe