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Ethnopharmacological Relevance: Olea europaea L. and Hyphaene thebaica L. are commonly employed by traditional healers in Africa for treating and preventing hypertension, either individually or in a polyherbal preparation (Ifanosine)., Aim of the Study: The primary aim was to assess the antihypertensive effects of Olea europaea L. leaves aqueous extract (OEL), Hyphaene thebaica L. mesocarp extract (HT), and the Ifanosine on isolated rat aorta rings. The secondary objective was to evaluate the clinical benefits of a new oral formulation of Ifanosine., Materials and Methods: In vitro studies using an isometric transducer examined the antihypertensive effects of HT, OEL, and Ifanosine on rat aorta. Ussing chambers technic were employed to measure mucosal to serosal fluxes and total transepithelial electrical conductance (Gt) to assess the intestinal bioavailability of HT, OEL, and Ifanosine. HPLC was utilized to determine the phytochemical composition of OEL and HT extracts. Subchronic toxicity investigations involved two groups of rats, treated with either water (control) or Ifanosine at 5 g/kg for 28 days. Clinical benefits of the new Ifanosine formulation were evaluated in an observational study with 32 hypertensive patients receiving a fixed oral dose of 3.5 mg three times a day for 30 days., Results: Aqueous extracts induced dose-dependent relaxation of rat aorta rings, with HT and OEL having higher IC50 values than Ifanosine (IC50 = 44.76 ± 1.35 ng/mL, 58.67 ± 1.02 ng/mL, and 29.46 ± 0.26 ng/mL, respectively). The pA2 values of OEL and HT were 1 and 0.6, respectively, while Ifanosine was 0.06. Intestinal bioavailability studies revealed better Prazosin bioavailability than plant extracts. Toxicological studies demonstrated the safety of Ifanosine, supported by histological examinations and biochemical parameters in rat blood. Biochemical analyses indicated flavonoids and phenolic acids as dominant active constituents. Clinical benefits in humans included reduced SBP, DBP, LDL-c, VLDL-c, and TAG, and increased HDL-c without overt adverse effects., Conclusion: This study validates the traditional use of OEL and HT for hypertension and advocates for alternative and combinatorial polyphytotherapy (ACP) to enhance traditional remedies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Medication adherence is vital for patients suffering from Chronic Obstructive Pulmonary Disease (COPD) to mitigate long-term consequences. The impact of poor medication adherence on inferior outcomes like exacerbations leading to hospital admissions is yet to be studied using real-world data. Using Swiss claims data from 2015-2020, we group patients into five categories according to their medication possession ratio. By employing a logistic regression, we quantify each category's average treatment effect of the medication possession ratio on hospitalized exacerbations. 13,557 COPD patients are included in the analysis. Patients with high medication adherence (daily medication reserve of 80% to 100%) are 51% less likely to incur exacerbation following a hospital stay than patients with the lowest medication adherence (daily medication reserve of 0% to 20%). The study shows that medication adherence varies strongly among Swiss COPD patients. Furthermore, high medication adherence immensely decreases the risk of hospitalized exacerbations., (© 2024. The Author(s).)

Non-small cell lung cancer is often diagnosed at advanced stages, and many patients are still treated with classical chemotherapy. The unselective nature of chemotherapy often results in severe myelosuppression. Previous studies showed that protein-coding mutations could not fully explain the predisposition to myelosuppression. Here, we investigate the possible role of enhancer mutations in myelosuppression susceptibility. We produced transcriptome and promoter-interaction maps (using HiCap) of three blood stem-like cell lines treated with carboplatin or gemcitabine. Taking advantage of publicly available enhancer datasets, we validated HiCap results in silico and in living cells using epigenetic CRISPR technology. We also developed a network approach for interactome analysis and detection of differentially interacting genes. Differential interaction analysis provided additional information on relevant genes and pathways for myelosuppression compared with differential gene expression analysis at the bulk level. Moreover, we showed that enhancers of differentially interacting genes are highly enriched for variants associated with differing levels of myelosuppression. Altogether, our work represents a prominent example of integrative transcriptome and gene regulatory datasets analysis for the functional annotation of noncoding mutations., (© 2024 Zhigulev et al.)

Background: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the FLCN gene coding for folliculin. Its clinical expression includes cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts, and recurrent spontaneous pneumothoraces. Data on lung function in BHD are scarce and it is not known whether lung function declines over time. We retrospectively assessed lung function at baseline and during follow-up in 96 patients with BHD., Results: Ninety-five percent of BHD patients had multiple pulmonary cysts on computed tomography and 59% had experienced at least one pneumothorax. Mean values of forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC ratio, and total lung capacity were normal at baseline. Mean (standard deviation) residual volume (RV) was moderately increased to 116 (36) %pred at baseline, and RV was elevated > 120%pred in 41% of cases. Mean (standard deviation) carbon monoxide transfer factor (DLco) was moderately decreased to 85 (18) %pred at baseline, and DLco was decreased < 80%pred in 33% of cases. When adjusted for age, gender, smoking and history of pleurodesis, lung function parameters did not significantly decline over a follow-up period of 6 years., Conclusions: Cystic lung disease in BHD does not affect respiratory function at baseline except for slightly increased RV and reduced DLco. No significant deterioration of lung function occurs in BHD over a follow-up period of 6 years.

Background: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) primarily due to tobacco smoking has been reported in connective tissue disease, but little is known about its characteristics in systemic sclerosis (SSc)., Methods: In this retrospective multi-center case-control study, we identified 36 SSc patients with CPFE, and compared them with 72 SSc controls with interstitial lung disease (ILD) without emphysema., Results: Rate of CPFE in SSc patients with CT scan was 3.6%, and 7.6% among SSc patients with ILD. CPFE-SSc patients were more likely to be male (75 % vs 18%, p < 0.0001), smokers (83 % vs 33%, p < 0.0001), and to have limited cutaneous SSc (53 % vs 24% p < 0.01) than ILD-SSc controls. No specific autoantibody was significantly associated with CPFE. At diagnosis, CPFE-SSc patients had a greater decrease in carbon monoxide diffusing capacity (DLCO 39 ± 13 % vs 51 ± 12% of predicted value, p < 0.0001) when compared to SSc-ILD controls, whereas lung volumes (total lung capacity and forced vital capacity) were similar. During follow-up, CPFE-SSc patients more frequently developed precapillary pulmonary hypertension (PH) (44 % vs 11%, p < 10 -4 ), experienced more frequent unscheduled hospitalizations (50 % vs 25%, p < 0.01), and had decreased survival (p < 0.02 by Kaplan-Meier survival analysis) as compared to ILD-SSc controls., Conclusions: The CPFE syndrome is a distinct pulmonary manifestation in SSc, with higher morbidity and mortality. Early diagnosis of CPFE by chest CT in SSc patients (especially smokers) may result in earlier smoking cessation, screening for PH, and appropriate management., (Copyright © 2018. Published by Elsevier Inc.)

Introduction: Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease affecting mainly young women., Background: The respiratory manifestations are characterized by a progressive cystic destruction of the lung parenchyma. Extrapulmonary involvement includes benign renal tumours called angiomyolipomas and abdominal lymphatic masses called lymphangioleiomyomas. At the pathological level, the cellular proliferation found in LAM is in part due to the presence of mutations in the tumour suppressor genes TSC1 and TSC2 (Tuberous Sclerosis Complex). These mutations lead to the activation of the mTOR pathway, which is currently the main therapeutic target. mTOR inhibitors such as sirolimus or everolimus have shown a beneficial effect on the decline in pulmonary function and a reduction of angiomyolipoma size, but are necessary in only some patients., Perspectives: LAM cells have migratory properties mediated by the formation of new lymphatic vessels. They are also able to secrete metalloproteases, which enhance their invasiveness. Moreover, the expression of estrogen and progesterone receptors by LAM cells suggests a possible role for sex hormones in the pathogenesis of the disease., Conclusion: A better understanding of mTOR-independent mechanisms would allow the development of novel therapeutic approaches., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Pulmonary Mucosa-Associated Lymphoid Tissue (MALT)-type lymphoma is the most frequent primary pulmonary lymphoma. We report the case of a patient who presented a pulmonary MALT-type lymphoma treated with chloraminophen, with a recurrence 5 years later characterized with pulmonary lesions associated with a gastric location. This observation underlines some anatomical and clinical aspects of pulmonary MALT-type lymphoma, and leads to discuss the evolution of its physiopathological and therapeutic concepts. In particular, the contributions of positron emission tomography and molecular biology allow the analysis of possible multifocal affections of this disease., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: In contrast to conventional laparoscopic partial nephrectomy, the approach of robot-assisted partial nephrectomy (RAPN) shows a steep learning curve with shorter warm ischaemia times (WIT) and comparable postoperative outcomes. Therefore RAPN is considered a good minimally-invasive surgical procedure for patients presenting with a renal cell carcinoma in clinical stage cT1a. The aim of the presented study was to evaluate the perioperative outcomes of our patients after RAPN and to illustrate the learning curve based on characteristic perioperative parameters such as WIT., Material and Methods: The data of 109 patients treated by RAPN in our clinic between January 2010 and April 2015 were retrospectively analysed regarding perioperative, laboratory and oncological outcomes. Postoperative complications until 30 days after surgery were documented. We analysed the data of the largest patient population treated by a single urologist, comparing WIT, operating time, blood loss and decline of the glomerular filtration rate between the first and the second 30 consecutive cases., Results: Mean WIT was 18.4 min (SD±10.2), mean operating time was 199 min (SD±20), and mean estimated blood loss was 657 millilitres (SD±715 ml). Mean loss of GFR was reported to be 4.99 mg/dl/1.73 m (2) (SD±15.44). 83 (76%) malignant lesions were removed. 11 patients (10%) had a R1 resection, one patient had a R2 resection and in 2 cases the resection status was Rx. 22% of patients developed postoperative complications. Intraoperative complications were documented in 2 cases. According to the Clavien-Dindo Classification, 6% of patients had grade 1 and 2 complications and 13% developed grade 3 and 4 complications. WIT was significantly lower after 30 consecutive cases treated by one urologist. Regarding operating time, GFR or blood loss no significant correlation was found., Conclusion: Our data is in line with the surgical outcomes described in the literature. RAPN is a safe surgical technique with a steep learning curve. In our experience, 30 surgical cases provide a urologist with sufficient expertise to achieve good perioperative results. Weaknesses of this report include the retrospective design and insufficient documentation in some cases., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Amyopathic dermatomyositis associated with anti-MDA5 autoantibodies is a rare and very recently described clinical entity., Case Report: A 58-year-old woman was admitted with subacute onset of dyspnea (NYHA class IV) associated with cough, oligoarthritis of the wrists, myalgia and intermittent fever. Examination demonstrated skin lesions with heliotrope rash, Gottron's papules, "mechanics hands", and basal inspiratory crackles on lung auscultation. Pulmonary function tests showed a restrictive ventilatory defect, with decreased carbon monoxide diffusion capacity and marked hypoxemia (PaO2 61 mmHg). The chest high-resolution computed tomography appearances were consistent with organizing pneumonia. Bronchoalveolar lavage differential cell count demonstrated 22 % neutrophils. Serum creatine kinase and electromyography were normal ; the serum ferritin level was elevated. Antinuclear antibodies were present and anti-MDA5 autoantibodies were identified. Significant improvement was obtained with systemic corticosteroids, later converted to mycophenolate mofetil as a steroid-sparing agent., Conclusion: Amyopathic dermatomyositis associated with anti-MDA5 autoantibodies shares some characteristics with those associated with anti-synthetase antibodies. Muscular involvement may be mild or absent. Early diagnosis and treatment may improve outcome., (Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.)