In-Flow Generation of Thionyl Fluoride (SOF2) Enables the Rapid and Efficient Synthesis of Acyl Fluorides from Carboxylic Acids.

Herein, we report an approach for generating thionyl fluoride (SOF2) from the commodity chemicals thionyl chloride (SOCl2) and potassium fluoride (KF). The methodology relies on a microfluidic device that can efficiently produce and dose this toxic gaseous reagent under extremely mild and safe conditions. Subsequently, the in situ-generated thionyl fluoride is reacted with an array of structurally and electronically differing carboxylic acids, leading to the direct and efficient synthesis of highly sought-after acyl fluorides. Importantly, our investigation also highlights the inherent modularity of this flow-based platform. We demonstrate the adaptability of this approach by not only synthesizing acyl fluorides but also directly converting carboxylic acids into a diverse array of valuable compounds such as esters, thioesters, amides, and ketones. This versatility showcases the potential of this approach for a wide range of synthetic applications, underscoring its significance in the realm of chemical synthesis.

A unified flow strategy for the preparation and use of trifluoromethyl-heteroatom anions.

The trifluoromethyl group (CF3) is a key functionality in pharmaceutical and agrochemical development, greatly enhancing the efficacy and properties of resulting compounds. However, attaching the CF3 group to heteroatoms such as sulfur, oxygen, and nitrogen poses challenges because of the lack of general synthetic methods and reliance on bespoke reagents. Here, we present a modular flow platform that streamlines the synthesis of heteroatom-CF3 motifs. Our method uses readily available organic precursors in combination with cesium fluoride as the primary fluorine source, facilitating the rapid generation of N-trifluoromethyl(R) [NCF3(R)], SCF3 (trifluoromethylthio), and OCF3 (trifluoromethoxy) anions on demand without reliance on perfluoroalkyl precursor reagents. This strategy offers a more environmentally friendly synthesis of trifluoromethyl(heteroatom)-containing molecules, with the potential for scalability in manufacturing processes facilitated by flow technology.

Revie ⊕: Impact of a resource-based life review intervention on patients with advanced cancer: A waitlist controlled trial.

PURPOSE: Life review interventions aim to support individuals facing an incurable disease accompanied by existential concerns and health-related challenges. Based on encouraging feasibility results, this study assessed the effects of Revie ⊕ life review intervention on the self-esteem of patients with advanced cancer, and the effects on well-being, post-traumatic growth, life satisfaction, symptom burden and interaction with nurses. METHOD: The study consisted of a two-arm parallel-group, waitlist-controlled trial (WCT) in the oncology division of a Swiss-French University Hospital. Revie ⊕ was composed of nurse-led meeting with the patient to address and document significant life events using a strengths-focused approach and targeting the life project. RESULTS: Due to Covid-19 pandemic, adjustments were made regarding study duration and participant's allocation: Fifty-eight patients received Revie ⊕, 39 completed all the measurements. Self-esteem was high at baseline and maintained stability over time. The social well-being decreased in the intervention group before-after Revie ⊕ (-1.7 (3.9), p = 0.044) while emotional and functional well-being showed stability. The intensity of symptoms decreased in the intervention group before-after Revie ⊕: 4.9 (9.4), p = 0.020. CONCLUSIONS: This study suggests that patients living with an advanced cancer and who received Revie ⊕ intervention may have maintained their self-esteem high over time. Observed results are promising, particularly considering the influence of the pandemic. Nevertheless, these findings do not allow us to draw definitive conclusions regarding the efficacy of the intervention on self-esteem. WCT seems not to be the appropriate design to highlight the added value of Revie ⊕ for this particularly vulnerable population. CLINICAL TRIAL REGISTRATION NUMBER: NCT04254926.

[Mindfulness meditation in somatic medicine. A management tool for physical and psychological pain]. / Applications de la méditation de pleine conscience dans différents secteurs de médecine somatique. Un outil de gestion de la douleur physique et morale.

Mindfulness meditation is a mind-body approach that helps to cope with psychological or physical symptoms such as pain. To date, this approach is still not widely available to patients in our French-speaking somatic clinical settings, despite its scientific validation. This article describes three mindfulness meditation programs delivered at Lausanne University Hospital (CHUV) to people living with HIV, cancer or chronic pain. It highlights the issues related to the involvement of participants in these programs as well as those related to their implementation in a Swiss somatic, teaching French-speaking hospital.

La méditation de pleine conscience est une approche corps-esprit qui permet de faire face à des symptômes psychiques ou physiques tels que la douleur. À ce jour, malgré sa validation scientifique, cette approche reste peu accessible pour les patient-e-s dans nos contextes cliniques somatiques romands. Cet article décrit trois programmes de méditation de pleine conscience délivrés au sein du CHUV (Lausanne), à des personnes qui vivent avec un VIH, un cancer ou une douleur chronique. Il met en lumière les enjeux liés à l'engagement des participant-e-s dans ces programmes mais aussi ceux en lien avec leur implémentation dans un contexte hospitalier somatique romand.

Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines.

The Pd-catalyzed N-arylation method for the synthesis of eighteen N,1-diaryl-1H-tetrazol-5-amine derivatives is reported. By running the reactions at 35 °C, compounds were isolated as single isomers since the undesired Dimroth rearrangement was completely suppressed. Furthermore, the Dimroth rearrangement of N,1-diaryl-1H-tetrazol-5-amines was rationalized by conducting comprehensive experiments and NMR analysis as well as density functional theory (DFT) calculations of thermodynamic stability of the compounds. It was established that the Dimroth rearrangement is thermodynamically controlled, and the equilibrium of the reaction is determined by the stability of the corresponding isomers. The mechanism was investigated by additional DFT calculations, and the opening of the tetrazole ring was shown to be the rate-determining step. By maneuvering Pd-catalyzed N-arylation and the subsequent Dimroth rearrangement, two more N,1-diaryl-1H-tetrazol-5-amine derivatives were acquired, which otherwise cannot be synthesized by employing the C-N cross-coupling reaction.

[Breast cancer: perspectives from integrative medicine]. / Cancer du sein: perspectives de médecine intégrative.

Integrative medicine combines the virtues of conventional medicine and complementary medicine in order to improve the quality of life of patients suffering from cancer. Thanks to a multidisciplinary and multi-professional team, the Center for integrative and complementary medicine (CEMIC) allows since 2017 cancer patients at CHUV to have access to certain therapies, for which there are sufficient data suggesting a benefit in terms of quality of life. The concepts of tolerance, safety, risk of interactions and potential adverse biological effects remain central. In this article, we discuss acupuncture, art therapy, mindfulness and some natural therapies that are encountered regularly.

La médecine intégrative propose aux patients touchés par le cancer une combinaison des soins offerts par la médecine conventionnelle et la médecine complémentaire avec comme objectif l'amélioration de la qualité de vie des patients. Grâce à des équipes multidisciplinaires et multiprofessionnelles, le Centre de médecine intégrative et complémentaire (CEMIC) permet depuis 2017 aux patients oncologiques du CHUV d'avoir accès à certaines thérapies pour lesquelles il existe des données suggérant un bénéfice en termes de qualité de vie. Les notions de tolérance aux traitements, de sécurité, de risque d'interactions et d'éventuels effets biologiques non souhaités restent centrales. Dans cet article, nous discutons de l'acupuncture, de l'art-thérapie, de la méditation et de certaines substances et thérapies naturelles rencontrées régulièrement.

Experiences of newly diagnosed cancer patients in confronting the finitudes of life: a qualitative systematic review protocol.

REVIEW QUESTION: What is the experience of newly diagnosed patients with cancer when facing the finitude of life and undergoing initial anti-cancer treatment?

Frequencies of EGFR single nucleotide polymorphisms in non-small cell lung cancer patients and healthy individuals in the Republic of Serbia: a preliminary study.

The purpose of this study was to determine the frequencies of EGFR -216G>T, -191C>A, and 181946C>T in Serbian non-small cell lung cancer (NSCLC) patients, as well as to compare it with healthy individuals, in order to assess their potential importance for lung cancer in Serbia. The study involved 56 NSCLC patients and 53 unrelated healthy volunteers, and genotyping was performed on DNA samples obtained from formalin-fixed paraffin-embedded lung tumor tissue and blood, respectively. This was the first time to show genotype frequencies of those single nucleotide polymorphisms for this study group from the territory of the Republic of Serbia. There was very strong evidence of association between age and death due to lung cancer (Pearson chi-square = 43.439, df = 2, p < 0,001), as well as between ever smoking and death due to lung cancer (Pearson chi-square = 31.727, df = 1, p < 0.001). When dominant genetic model (GG vs. GT+TT) was used for -216G>T, we have found significant association (p = 0.012) between -216GG genotype and NSCLC patients within smokers' subgroup. So, carriers of -216GG genotype had higher risk (OR = 4.33, 95 % CI = 1.324-14.179) than noncarriers (GT and TT) for developing non-small cell lung cancer in our patients.

Pneumothorax after transbronchial needle biopsy.

Currently there several diagnostic techniques that re used by radiologists and pulmonary physicians for lung cancer diagnostics. In several cases pneumothorax (PNTX) is induced and immediate action is needed. Both radiologists and pulmonary physicians can insert a chest tube for symptom relief. However; only pulmonary physicians and thoracic surgeons can provide a permanent solution for the patient. The final solution would be for a patient to undergo surgery for a final solution. In our current work we will provide all those diagnostic cases where PNTX is induced and treatment from the point of view of expert radiologists and pulmonary physicians.

Successful treatment of pseudomembranous necrotizing aspergillus tracheobronchitis in a patient with acute myeloid leukemia.

INTRODUCTION: Pseudomembranous necrotizing Aspergillus tracheobronchitis is a rare form of pulmonary aspergillosis which occurs in immunocompromised patients. CASE OUTLINE: A female patient aged 71, suffering from acute myeloid leukemia, developed the symptoms of progressive shortness of breath and inspiratory stridor. The diagnosis in our case was made on the histological findings from tissues obtained by bronchoscopy. A chest CT scan suggested the state of the compromised trachea and left principal bronchus lumen. The long-term regimen with itraconazole in the dose of 400 mg/24 hours proved efficient in our patient. CONCLUSION: Progressive shortness of breath and inspiratory stridor in immunocompromised patients along with radiological and CT changes should be also considered as pulmonary aspergillosis in differential diagnosis.

Pneumothorax after transthoracic needle biopsy of lung lesions under CT guidance.

Transthoracic needle biopsy (TTNB) is done with imaging guidance and most frequently by a radiologist, for the aim is to diagnose a defined mass. It is integral in the diagnosis and treatment of many thoracic diseases, and is an important alternative to more invasive surgical procedures. FNAC is a method of aspiration cytopathology, which with transthoracic biopsy ("core biopsy") is a group of percutaneous minimally invasive diagnostic procedures for exploration of lung lesions. Needle choice depends mostly upon lesion characteristics and location. A recent innovation in biopsy needles has been the introduction of automatic core biopsy needle devices that yield large specimens and improve the diagnostic accuracy of needle biopsy. Both computed tomography and ultrasound may be used as imaging guidance for TTNB, with CT being more commonly utilized. Common complications of TTNB include pneumothorax and hemoptysis. The incidence of pneumothorax in patients undergoing TTNB has been reported to be from 9-54%, according to reports published in the past ten years, with an average of around 20%. Which factors statistically correlate with the frequency of pneumothorax remain controversial, but most reports have suggested that lesion size, depth and the presence of emphysema are the main factors influencing the incidence of pneumothorax after CT-guided needle biopsy. On the contrary, gender, age, and the number of pleural passes have not been shown to correlate with the incidence of pneumothorax. The problem most responsible for complicating outpatient management, after needle biopsy was performed, is not the presence of the pneumothorax per se, but an increase in the size of the pneumothorax that requires chest tube placement and patient hospitalization. Although it is a widely accepted procedure with relatively few complications, precise planning and detailed knowledge of various aspects of the biopsy procedure is mandatory to avert complications.

Patient-related independent clinical risk factors for early complications following Nd: YAG laser resection of lung cancer.

INTRODUCTION: Neodymium:yttrium aluminum garnet (Nd:YAG) laser resection is one of the most established interventional pulmonology techniques for immediate debulking of malignant central airway obstruction (CAO). The major aim of this study was to investigate the complication rate and identify clinical risk factors for complications in patients with advanced lung cancer. METHODS: In the period from January 2006 to January 2011, data sufficient for analysis were identified in 464 patients. Nd:YAG laser resection due to malignant CAO was performed in all patients. The procedure was carried out in general anesthesia. Complications after laser resection were defined as severe hypoxemia, global respiratory failure, arrhythmia requiring treatment, hemoptysis, pneumothorax, pneumomediastinum, pulmonary edema, tracheoesophageal fistulae, and death. Risk factors were defined as acute myocardial infarction within 6 months before treatment, hypertension, chronic arrhythmia, chronic obstructive pulmonary disease (COPD), stabilized cardiomyopathy, previous external beam radiotherapy, previous chemotherapy, and previous interventional pulmonology treatment. RESULTS: There was 76.1% male and 23.9% female patients in the study, 76.5% were current smokers, 17.2% former smokers, and 6.3% of nonsmokers. The majority of patients had squamous cell lung cancer (70%), small cell lung cancer was identified in 18.3%, adenocarcinoma in 3.4%, and metastases from lung primary in 8.2%. The overall complication rate was 8.4%. Statistically significant risk factors were age (P = 0.001), current smoking status (P = 0.012), arterial hypertension (P < 0.0001), chronic arrhythmia (P = 0.034), COPD (P < 0.0001), and stabilized cardiomyopathy (P < 0.0001). Independent clinical risk factors were age over 60 years (P = 0.026), arterial hypertension (P < 0.0001), and COPD (P < 0.0001). CONCLUSION: Closer monitoring of patients with identified risk factors is advisable prior and immediately after laser resection. In order to avoid or minimize complications, special attention should be directed toward patients who are current smokers, over 60 years of age, with arterial hypertension or COPD.

Autofluorescence imaging videobronchoscopy in the detection of lung cancer: from research tool to everyday procedure.

Autofluorescence imaging videobronchoscopy (AFI) is one of the new systems of autofluorescence bronchoscopy designed for thorough examination of bronchial mucosa. The integration of autofluorescence and videobronchoscopy provides clear images of normal and pathologically altered bronchial mucosa. Major indications for AFI include evaluation of early-stage lung cancer and detection of precancerous lesions. However, in recent years, the indications for AFI are widening, and this tool might find its place in routine daily bronchoscopic practice. With new indications for AFI, such as evaluation of tumor extension or follow-up after surgical resection, this tool might be more often used by bronchoscopists. A sharp learning curve and clear distinction between healthy and pathologically altered mucosa make this technology acceptable for young and inexperienced bronchoscopists. One of the major disadvantages of AFI is low specificity in the detection of premalignant lesions and early-stage lung cancer. This disadvantage could be overcome with the appearance of new and improved technologies in autofluorescence, such as the addition of backscattered light analysis, ultraviolet spectra, fluorescence-reflectance or dual digital systems. Quantitative image analysis is also one of the ways to improve objectivity and minimize observer errors. However, one of the most appropriate solutions would be the addition of AFI to narrow band imaging, and merging the two technologies into one videobronchoscope.

Clinical trials in advanced stage lung cancer: a survey of patients' opinion about their treatment.

BACKGROUND: The major aim of this study was to investigate what patients with advanced stage lung cancer, enrolled in a clinical trial, thought about their treatment. We also wanted to investigate if there exist any characteristics that could influence patients' opinion about the clinical trial. PATIENTS AND METHODS: Over the period from June 2008 to June 2009, 59 eligible patients were enrolled in this study. The major inclusion criteria were: participation in a clinical trial, previously treated advanced stage lung cancer, and good performance status (ECOG 0-2). All patients were asked to answer a questionnaire designed to investigate their impressions about participation in a clinical trial. The questionnaire was deposited in a sealed box which was opened at the end of the study.We investigated a possible influence of age, gender, education, lung cancer stage, chemotherapy line and tumor type on the patients' opinion about some aspects of the clinical trial. RESULTS: The majority of the patients were aware they were participating in the clinical trial and a significant number of them were very satisfied with the treatment. Of the investigated factors, only the level of education had a statistically significant influence on some of the questions raised in the questionnaire. CONCLUSIONS: Patients participating in clinical trials are satisfied with their treatment, ready to proceed with it and would recommend it to other patients. It depends mainly on health professionals to maintain this level of confidence and justify their trust.

Intrathoracic malignant peripheral nerve sheath tumor with poor outcome: a case report.

We report a case of intrathoracic malignant peripheral nerve sheath tumor in a 65-year old woman revealed after a few-month history of progressive dyspnea, appetite and body mass loss. The chest magnetic resonance (MR) examination revealed the presence of a large tumor occupying the mediastinum and a major portion of the right hemithorax. The diagnostic tumor sample was obtained by parasternal biopsy in local anesthesia. The surgical resection of the tumor could not be performed due to its excessive size, intrathoracic involvement and bad respiratory reserves of a patient. The chemotherapy and irradiation were performed as palliative measures. The lethal outcome appeared 10 months after the diagnosis was established.