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Correspondence Regarding Lee et al.: Placebo Control is Vital in Assessing Therapy in Chronic Cough.Lung Jul 2024
PubMed: 38955862
DOI: 10.1007/s00408-024-00726-x -
The Oncologist Jul 2024With the widespread use of next-generation sequencing (NGS) for solid tumors, mesenchymal-to-epithelial transition factor (MET) rearrangement/fusion has been confirmed...
With the widespread use of next-generation sequencing (NGS) for solid tumors, mesenchymal-to-epithelial transition factor (MET) rearrangement/fusion has been confirmed in multiple cancer types. MET amplification and MET exon 14 skipping mutations induce protein autophosphorylation; however, the pathogenic mechanism and drug sensitivity of MET fusion remain unclear. The following report describes the clinical case of a patient diagnosed with squamous lung cancer bearing a TFG-MET gene fusion. In vitro assays demonstrated MET phosphorylation and oncogenic capacity due to the TFG-MET rearrangement, both of which were inhibited by crizotinib treatment. The patient was treated with crizotinib, which resulted in sustained partial remission for more than 17 months. Collectively, cellular analyses and our case report emphasize the potential of MET fusion as a predictive biomarker for personalized target therapy for solid tumors.
PubMed: 38954846
DOI: 10.1093/oncolo/oyae166 -
Hepatology (Baltimore, Md.) Jul 2024Alpha-1 antitrypsin deficiency (A1ATD) is a life-threatening condition caused by inheritance of the SERPINA1 'Z' genetic variant (PiZ) driving AAT protein misfolding in...
Alpha-1 antitrypsin deficiency (A1ATD) is a life-threatening condition caused by inheritance of the SERPINA1 'Z' genetic variant (PiZ) driving AAT protein misfolding in hepatocytes. There remain no approved medicines for this disease. Here, we report the results of a small molecule screen performed in patient derived iPSC-hepatocytes that identified Leucine-rich repeat kinase-2 (LRRK2) as a potentially new therapeutic target. Of the commercially available LRRK2 inhibitors tested, we identified CZC-25146, a candidate with favorable pharmacokinetic properties, as being capable of reducing polymer load, increasing normal AAT secretion, and reducing inflammatory cytokines in both cells and PiZ mice. Mechanistically, this effect was achieved through induction of autophagy. Our findings support the use of CZC-25146 and LRRK2 inhibitors in hepatic proteinopathy research and their further investigation as novel therapeutic candidates for A1ATD.
PubMed: 38954820
DOI: 10.1097/HEP.0000000000000969 -
The Journal of Pharmacy and Pharmacology Jul 2024The management of asthma and chronic obstructive pulmonary disease (COPD) poses considerable challenges due to the intricate nature of these respiratory conditions....
The management of asthma and chronic obstructive pulmonary disease (COPD) poses considerable challenges due to the intricate nature of these respiratory conditions. Fostair™ and Trimbow™, two pressurized metered dose inhalers, have emerged as noteworthy therapeutic options for treating both asthma and COPD. Fostair combines an inhaled corticosteroid, specifically beclometasone dipropionate, with a long-acting beta2-agonist, formoterol fumarate dihydrate, offering a dual-action approach to mitigate airway inflammation and bronchoconstriction. Conversely, Trimbow integrates a tri-particulate formulation consisting of beclometasone dipropionate, formoterol fumarate dihydrate, and glycopyrronium bromide, providing a comprehensive strategy to target the pathophysiology of COPD and asthma. Recent clinical trials have underscored Trimbow's superior efficacy compared with Fostair, particularly in terms of reducing exacerbation rates and enhancing lung function. However, despite their therapeutic promise, both inhalers encounter challenges, including limited generalizability of study findings and a disparity between in vitro and human trial results. This literature review offers an in-depth analysis of Fostair and Trimbow, delving into their mechanisms of action, clinical applications, and outcomes in human studies for asthma and COPD. Additionally, the review discusses the role of combination therapy in managing respiratory diseases and underscores the necessity for further research to address existing knowledge gaps and optimize therapeutic outcomes.
PubMed: 38954755
DOI: 10.1093/jpp/rgae090 -
Current Oncology Reports Jul 2024Immune-related adverse events (irAEs) are pivotal in the management of immune checkpoint inhibitors (ICIs) across various human neoplasms. While common irAEs are... (Review)
Review
PURPOSE OF REVIEW
Immune-related adverse events (irAEs) are pivotal in the management of immune checkpoint inhibitors (ICIs) across various human neoplasms. While common irAEs are manageable by oncologists, the detailed features of rare complications related to ICI therapy remain elusive. Among these, immune-related myasthenia gravis (irMG) stands out as a life-threatening disease.
RECENT FINDINGS
Research articles published in English between 2017 and 2023 were identified using the PubMed database. Forty-six relevant research studies were examined to collate information for this review. The incidence of ICI-induced MG was found to be less than 1.0%, with approximately 20-30% of irMG patients presenting with overlap syndrome involving myocarditis and myositis. The detection of acetylcholine receptor antibodies (AChR-Ab) and elevated creatinine kinase (CK) levels proved useful in identifying 50-70% and 60-80% of cases, respectively. However, the utility of muscle-specific kinase antibodies (MuSK-Ab) in detecting irMG was limited due to a low positivity rate (0-5.3%). Ptosis emerged as the most common initial symptom of irMG, with an approximate positivity rate of 80%. Recommended treatment for irMG involves high-dose steroids in conjunction with plasmapheresis or immunoglobulins to mitigate the increased mortality associated with irMG. Early initiation of immunosuppressive therapy is imperative to prevent the worsening of irMG. Furthermore, facilitating a fulfilling social life post-hospitalization is crucial. This review sheds light on the clinical aspects and management strategies pertaining to irMG.
PubMed: 38954314
DOI: 10.1007/s11912-024-01571-0 -
Multidisciplinary Respiratory Medicine Jul 2024Lung ultrasound (LUS) is a non-invasive point of care diagnostic tool used to assess the presence and severity of various lung disorders for more than two decades....
BACKGROUND
Lung ultrasound (LUS) is a non-invasive point of care diagnostic tool used to assess the presence and severity of various lung disorders for more than two decades. Within the healthcare professionals are the respiratory therapists (RTs) who play a vital role in managing ventilated and other patients requiring respiratory support, but the incorporation of LUS into their scope of practice has not been well highlighted. This international cross-sectional survey was specifically designed to evaluate the knowledge, attitude, and practice of RTs with respect to LUS.
METHODS
This observational cross-sectional study was conducted among RTs from different parts of the world using a questionnaire-based study tool. 514 RTs responded to all the questions and were considered for statistical analysis. Descriptive statistics, Analysis of variance, Fisher's exact, Chi-square, Bonferroni post-hoc analysis, and Binomial logistic regression analyses were performed to identify the significance of the data.
RESULTS
From 22 countries, 514 RTs responded to the survey, with the major share from the middle eastern countries. Out of the 514 responders, 44.9% of the responders were in the age group of 23-30 years; 67.1% were bachelor's degree holders; and 40.9% of participants had more than 10 years of experience. The knowledge-based questions revealed that RTs with higher experience and academic qualification provided more positive responses. While in the attitude-related domain it is observed that standardized training in LUS helps them to enhance the current practice and to add LUS to the academic curriculum of respiratory therapy schools; however there remains barriers to practice LUS based on their responses. The practice-based questions revealed that RTs expect some additional seminars/workshops/webinars to be done on LUS frequently. More than half of the participants are found to be knowledgeable with a positive attitude and working towards the inclusion of LUS in respiratory therapy profession.
CONCLUSION
It is concluded that respiratory therapists have a positive attribute towards the inclusion of lung ultrasound in their clinical practice. Providing more structured training for professional respiratory therapists and including lung ultrasound modules in the respiratory therapy school curriculum may facilitate mastering their diagnostic skills, thereby expanding the scope of practice.
PubMed: 38953856
DOI: 10.5826/mrm.2024.980 -
Indian Journal of Public Health Apr 2024We conducted the study to assess the effect of patient-tailored diet counseling on the nutritional status of chronic respiratory disease (CRD) patients under the...
Effect of Diet Counseling on Nutritional Status of Chronic Respiratory Diseases Patients Enrolled in the Pulmonary Rehabilitation Program in a Teaching Hospital: A Pre-Post Intervention Study.
We conducted the study to assess the effect of patient-tailored diet counseling on the nutritional status of chronic respiratory disease (CRD) patients under the pulmonary rehabilitation program from June 2021-May 2022. These patients completed 2 months of patient-tailored diet counseling sessions under the pulmonary rehabilitation program, which consisted of 4-5 interactive diet counseling sessions fortnightly. The pre- and postassessment was done using standardized outcomes: Malnutrition Universal Screening Tool (MUST), body mass index (BMI), and ideal body weight. The study enrolled 110 CRD patients. There was a statistically significant improvement in pre- and postassessment in MUST score, appetite, and unintentional weight loss (P < 0.001). Most of the patient's BMI normalized. In prenutritional assessment, most of the patients were malnourished and in postassessment, the number of malnourished and anemic patients was reduced. This study concludes that nutritional counseling effectively improves nutritional status and anemia.
Topics: Humans; Female; Male; Nutritional Status; Hospitals, Teaching; Middle Aged; Counseling; Malnutrition; Body Mass Index; Chronic Disease; Aged; Adult; India; Nutrition Assessment; Anemia
PubMed: 38953821
DOI: 10.4103/ijph.ijph_45_23 -
Journal of Bronchology & Interventional... Jul 2024CT-to-body divergence-described as the difference between preprocedural CT scans and intraprocedural lung architecture-is a significant barrier to improving diagnostic... (Observational Study)
Observational Study
BACKGROUND
CT-to-body divergence-described as the difference between preprocedural CT scans and intraprocedural lung architecture-is a significant barrier to improving diagnostic yield during navigational bronchoscopy. A major proposed contributor to CT-to-body divergence is the development of atelectasis, which can confound visualization of peripheral lung lesions via radial probe endobronchial ultrasound (RP-EBUS). High positive end-expiratory pressure (PEEP) ventilatory strategies have been used to decrease atelectasis, allowing the lesion to re-APPEAR on intraprocedure imaging. However, standardized PEEP levels may not be appropriate for all patients due to hemodynamic and ventilatory impacts.
METHODS
We performed a multicenter, prospective observational study in which patients were imaged with RP-EBUS under general anesthesia to determine if subsegmental atelectasis would resolve as incremental increases in PEEP were applied. Resolution of atelectasis was based on the transition from a non-aerated pattern to an aerated appearance on RP-EBUS. RP-EBUS images were reviewed by 3 experienced operators to determine correlation.
RESULTS
Forty-three patients underwent RP-EBUS examination following navigational bronchoscopy. Thirty-seven patients underwent incremental PEEP application and subsequent RP-EBUS imaging. Atelectasis was determined to have resolved in 33 patients (88.2%) following increased PEEP. The intraclass correlation coefficient between reviewers was 0.76. A recruitment maneuver was performed in 7 (16.3%) patients after atelectasis persisted at maximal PEEP. Atelectasis was not identified in the examined subsegments in 6 (10.8%) patients despite zero PEEP.
CONCLUSION
RP-EBUS is an effective tool to monitor what pressure atelectasis within a lung segment has resolved with increasing levels of PEEP.
Topics: Humans; Positive-Pressure Respiration; Pulmonary Atelectasis; Bronchoscopy; Prospective Studies; Male; Female; Aged; Middle Aged; Endosonography; Tomography, X-Ray Computed
PubMed: 38953737
DOI: 10.1097/LBR.0000000000000969 -
Ugeskrift For Laeger Jun 2024This case report describes laryngeal oedema occurring in a 35-year-old woman with chronic bowel-associated dermatosis-arthritis syndrome, and stenosis of the left main...
This case report describes laryngeal oedema occurring in a 35-year-old woman with chronic bowel-associated dermatosis-arthritis syndrome, and stenosis of the left main bronchus. The oedema was attributed to persistent cough exacerbated by delayed treatment and intubation-related irritation. Evaluations ruled out inflammatory, autoimmune, and malignant causes. Literature lacks on specific descriptions of cough-induced laryngeal oedema, emphasizing the need for a multidisciplinary approach and early intervention in complex cases to prevent severe hospitalizations in patients with known serious conditions and symptom exacerbation.
Topics: Humans; Adult; Female; Cough; Laryngeal Edema; Respiration, Artificial; Intubation, Intratracheal
PubMed: 38953687
DOI: 10.61409/V12230792 -
General Physiology and Biophysics Jul 2024Chronic obstructive pulmonary disease (COPD), characterized by clinical sub-phenotypes such as emphysema (E) and chronic bronchitis (CB), is associated with a greater...
Chronic obstructive pulmonary disease (COPD), characterized by clinical sub-phenotypes such as emphysema (E) and chronic bronchitis (CB), is associated with a greater risk of lung cancer (LC). This study aimed to assess the expression patterns of circRNA and their potential functional involvement in LC patients with COPD. A circRNA microarray was used to characterize differentially expressed circRNAs (DEcircRNAs) profiles. A total of 176, 240, 163, and 243 DEcircRNAs were identified in comparisons between CB vs. LC patients (Con), E vs. Con, E vs. CB, and CBE vs. Con, respectively. DEcircRNAs in all comparison groups were primarily associated with immune-related GO terms and were also enriched in immune and inflammatory pathways. In total, 49 DEcircRNAs were significantly correlated with the infiltration of multiple immune cells. Among them, hsa-MROH9_0001 and hsa-RP11-35J10_0013 were positively and negatively correlated with plasma cells and T-cell CD4 memory resting cells, respectively; these two DEcircRNA-sponged miRNAs have good diagnostic performance. WGCNA identified six key circRNAs associated with CB progression. The expression patterns of hsa-MROH9_0001 and circRNA_21729 in E and CB groups were confirmed by RT-qPCR. In conclusion, we reported circRNA profiles and the findings demonstrated that hsa-MROH9_0001 and circRNA_21729 may be potential therapeutic targets for LC with COPD.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; RNA, Circular; Lung Neoplasms; Pilot Projects; Male; Female; Aged; Gene Expression Profiling; Middle Aged; Transcriptome; Gene Expression Regulation, Neoplastic
PubMed: 38953571
DOI: 10.4149/gpb_2024013