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Background: LAMA2-related dystrophies (LAMA2-RDs) represent one of the most common forms of congenital muscular dystrophy and have historically been classified into two subtypes: complete or partial deficiency of laminin-211 (merosin). Patients with LAMA2-RD with the typical congenital phenotype manifest severe muscle weakness, delayed motor milestones, joint contractures, failure to thrive, and progressive respiratory insufficiency. Objective: While a comprehensive prospective natural history study has been performed in LAMA2-RD patients over 5 years of age, the early natural history of patients with LAMA2-RD 5 years and younger has not been comprehensively characterized. Methods: We extracted retrospective data for patients with LAMA2-RD ages birth through 5 years via the Congenital Muscle Disease International Registry (CMDIR). We analyzed the data using a phenotypic classification based on maximal motor milestones to divide patients into two phenotypic groups: "Sit" for those patients who attained that ability to remain seated and "Walk" for those patients who attained the ability to walk independently by 3.5 years of age. Results: Sixty patients with LAMA2-RD from 10 countries fulfilled the inclusion criteria. Twenty-four patients had initiated non-invasive ventilation by age 5 years. Hospitalizations during the first years of life were often related to respiratory insufficiency. Feeding/nutritional difficulties and orthopedic issues were commonly reported. Significant elevations of creatine kinase (CK) observed during the neonatal period declined rapidly within the first few months of life. Conclusions: This is the largest international retrospective early natural history study of LAMA2-RD to date, contributing essential data for understanding early clinical findings in LAMA2-RD which, along with the data being collected in international, prospective early natural history studies, will help to establish clinical trial readiness. Our proposed nomenclature of LAMA2-RD1 for patients who attain the ability to sit (remain seated) and LAMA2-RD2 for patients who attain the ability to walk independently is aimed at further improving LAMA2-RD classification.

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The issue of left against medical advice (LAMA) patients is common in today's emergency departments (EDs). This issue represents a medico-legal risk and may result in potential readmission, mortality, or revenue loss. Thus, understanding the factors that cause patients to "leave against medical advice" is vital to mitigate and potentially eliminate these adverse outcomes. This paper proposes a framework for studying the factors that affect LAMA in EDs. The framework integrates machine learning, metaheuristic optimization, and model interpretation techniques. Metaheuristic optimization is used for hyperparameter optimization-one of the main challenges of machine learning model development. Adaptive tabu simulated annealing (ATSA) metaheuristic algorithm is utilized for optimizing the parameters of extreme gradient boosting (XGB). The optimized XGB models are used to predict the LAMA outcomes for patients under treatment in ED. The designed algorithms are trained and tested using four data groups which are created using feature selection. The model with the best predictive performance is then interpreted using the SHaply Additive exPlanations (SHAP) method. The results show that best model has an area under the curve (AUC) and sensitivity of 76% and 82%, respectively. The best model was explained using SHAP method.

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BACKGROUND: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS. METHODS: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA. RESULTS: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters. CONCLUSION: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.

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Background: LAMA2-related muscular dystrophy (LAMA2-RD) is an autosomal-recessive disorder and one of the most common congenital muscular dystrophies. Due to promising therapies in preclinical development, there is an increasing effort to better define the epidemiology and natural history of this disease. Objective: The present study aimed to describe a well-characterized baseline cohort of patients with LAMA2-RD in Switzerland. Methods: The study used data collected by the Swiss Registry for Neuromuscular Disorders (Swiss-Reg-NMD). Diagnostic findings were derived from genetics, muscle biopsy, creatine kinase-level and electrophysiological testing, as well as from brain MRIs. Further clinical information included motor assessments (CHOP INTEND, MFM20/32), joint contractures, scoliosis, ophthalmoplegia, weight gain, feeding difficulties, respiratory function, cardiac investigations, EEG findings, IQ and schooling. Results: Eighteen patients with LAMA-RD were included in the Swiss-Reg-NMD as of May 2023 (age at inclusion into the registry: median age 8.7 years, range 1 month - 31 years F = 8, M = 10). Fourteen patients presented with the severe form of LAMA2-RD (were never able to walk; CMD), whereas four patients presented with the milder form (present or lost walking capability; LGMD). All patients classified as CMD had symptoms before 12 months of age and 11/14 before the age of six months. 15 carried homozygous or compound heterozygous pathogenic or likely pathogenic variants in LAMA2 and two were homozygous for a variant of unknown significance (one patient unknown). Brain MRI was available for 14 patients, 13 had white matter changes and 11 had additional structural abnormalities, including cobblestone malformations, pontine hypoplasia and an enlarged tegmento-vermial angle not reported before. Conclusion: This study describes the Swiss cohort of patients with LAMA2-RD and gives insights into measuring disease severity and disease progression, which is important for future clinical trials, as well as for a better clinical understanding and management of patients with LAMA2-RD.

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BACKGROUND: LAMA2-related dystrophies (LAMA2-RD) are a rare group of neuromuscular disorders with a broad spectrum of phenotype severity, ranging from mild to severe. We performed a cross-sectional study of LAMA2-RD through motor function and pulmonary tests to establish the disease's natural history. METHODS: Forty-four individuals with LAMA2-RD were included and evaluated once through functional outcome measures including Motor Function Measure 32 (MFM32), Revised Upper Limb Module (RULM), goniometry, and Forced Vital Capacity (FVC). Fixed Effect Regression Model (ERM) and Kaplan-Meier curve were used for calculating the rate of the disease progression RESULTS: Patients were between 2 and 25 years old (mean 11.4), the most frequent phenotype presentation was non-ambulant (N=36, 81.8%) while eight patients (18,2 %) were ambulant. The non-ambulant group presented a more severe progression of the disease. Non-ambulant patients had a 1.85 % decrease in FVC/year against 1.32 %/year among ambulant patients. In the non-ambulant group, there was a 4.2 % drop/year in the MFM32-D2 domain (p<0.00001), a 2.6 % drop/year in the D3 domain (p<0.0001), and a 2.7 % drop/year in the MFM32 global assessment (p<0.0001). However, the non-ambulant group's evaluation of upper limb function through the RULM scale did not show a statistically significant reduction. In the non-ambulant group, elbow and knee retractions worsened 3.22 degrees/year (p=0.00087) and 1.92 degrees/year, respectively. While in those patients who acquired gait, elbow and knee retractions worsened 2.45 degrees/year (p=0.0003) and 1.73 degrees/year (p=0.01), respectively. CONCLUSION: This study confirmed the progressive nature of LAMA2-RD, both in ambulant and non-ambulant patients. MFM32, FVC, and goniometry were identified as promising outcome measures for natural history studies and clinical trials in LAMA2-RD.

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OBJECTIVE: In Japan, the optimal initiation timing and efficacy of single-inhaler triple therapy (SITT) in asthma management remain unexplored. This study investigated SITT initiation timing following an asthma exacerbation, and examined patient demographics and clinical characteristics. METHODS: Observational, retrospective cohort study in patients with asthma aged ≥15 years who initiated SITT following their earliest observed asthma exacerbation (February-November 2021), using data from Japanese health insurance claims databases (JMDC and Medical Data Vision [MDV]). The study period ended May 2022 for JMDC and September 2022 for MDV. Descriptive analyses were performed independently by database. Variables evaluated included timing of SITT initiation post exacerbation (prompt, delayed and late, ≤30, 31-180 and >180 days post index, respectively), patient demographics, clinical characteristics, and pre-index treatment. RESULTS: Of patients in the JMDC and MDV databases, most initiated SITT promptly after an asthma exacerbation, 60.8% (n = 951/1565) and 44.4% (n = 241/543), respectively. Delayed initiation occurred in 22.6% (n = 354/1565) and 26.3% (n = 143/543) of patients, and late initiation occurred in 16.6% (n = 260/1565) and 29.3% (n = 159/543), respectively. Most patients were indexed on a moderate asthma-related exacerbation, 97.1% (n = 1519/1565) and 68.7% (n = 373/543), respectively. CONCLUSION: Most patients with asthma initiated SITT promptly following a moderate exacerbation, with delayed and late initiation more common among patients with complex clinical profiles. The findings underscore the necessity for future research to examine the interaction between patient characteristics, clinical outcomes, and the timing of SITT initiation to optimize treatment strategies, as clinical practice may vary by exacerbation severity.

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BACKGROUND: At present, immunotherapy has become a powerful treatment for advanced gastric cancer (AGC), but not all patients can benefit from it. According to the latest research, the impact of B cell subpopulations on the immune microenvironment of gastric cancer (GC) is unknown. Exploring whether the interaction between B cells and tumor cells in GC affects the effectiveness of immunotherapy has attracted our interest. METHODS: This study involved the re-analysis of single-cell RNA (scRNA) and spatial transcriptomics (ST) data from publicly available datasets. The focus was on investigating the subpopulations and differentiation trajectories of B cells in the gastric cancer (GC) tumor immune microenvironment (TIME). Spatial transcriptomics (ST) and multiple immunofluorescence (mIF) revealed a clear co-localization pattern between B cells and tumor cells. Multiple immunotherapy datasets were collected to identify unique immunotherapy biomarkers. The unique immunotherapeutic potential of targeting CCL28 was validated through a mouse gastric cancer model. In addition, flow cytometry revealed changes in the tumor immune microenvironment targeting CCL28. RESULTS: The re-analysis of ST data from multiple cancer types revealed a co-localization pattern between B cells and tumor cells. A significant number of IgA plasma cells were identified in the GC TIME. Five different tumor-infiltrating B cell subpopulations and two unique B cell differentiation trajectories were characterized, along with seven GC-related states. By analyzing the communication between GC cells and B cells, it was further discovered that tumor cells can influence and recruit plasma cells through CCL28-CCR10 signaling. Additionally, there was a crosstalk between GC cells and B cells. Finally, we identified the LAMA/CD44 signaling axis as a potential prognostic marker for immunotherapy through a large amount of immunotherapy data. We also validated through various animal tumor models that targeting CCL28 can significantly promote CD8+T cell infiltration and function in the TME by regulating B cell and plasma cell functions, and has the ability to synergize immunotherapy. CONCLUSION: The co-localization and crosstalk between GC cells and B cells significantly affect the efficacy of immunotherapy, and inhibiting the CCL28-CCR10 signal axis is a potential immunotherapy target for GC. Meanwhile, LAMA/CD44 pair may be a potential adverse indicator for immunotherapy and tumor prognosis.

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BACKGROUND AND STUDY AIMS: Laminin is an extracellular matrix molecule that is the major component of the basement membrane and plays a key role in regulating various processes. However, the association between the laminin gene family and the prognosis of pancreatic carcinoma has not been systematically investigated. PATIENTS AND METHODS: The role of the laminin gene family in pancreatic cancer was evaluated using data from the TCGA database. The effects of different expressions of members of the laminin gene family on pancreatic cancer survival were compared, and their primary cellular roles were examined. The effects of different expressions of positive family genes on proliferation, metastasis, and invasion, as well as EMT and ferroptosis in pancreatic cancer, were also examined. RESULTS: Based on univariate and multifactorial analysis of pancreatic cancer patients, LAMA3 was identified as an independent prognostic factor for overall survival in pancreatic cancer. LAMA3 was found to be enriched in the actin cytoskeleton, P53 signaling pathway, adhesion molecule junctions, pentose phosphate pathway, and regulatory differences in the cell cycle and focal adhesion. Additionally, high expression of LAMA3 was found to promote cancer proliferation, invasion, and metastasis, facilitate the EMT process, and inhibit ferroptosis. CONCLUSIONS: Our results identified LAMA3 was associated with the prognosis of patients with pancreatic cancer and may serve as a prognostic biomarker for pancreatic cancer.

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Mutations in the alpha-2 subunits of the laminin gene (LAMA2) cause an autosomal recessive congenital muscular dystrophy (CMD) subtype known as laminin a2-related muscular dystrophies (LAMA2-RD). LAMA2-RD can present with a wide range of phenotypes ranging from severe infantile congenital muscular dystrophy to milder adult-onset limb-girdle muscular dystrophy. This case describes a 28-year-old Indian gentleman having childhood-onset focal seizures, gradually progressive proximal predominant lower-limb weakness for the past three years, elevated creatinine phosphokinase levels, and MRI brain suggestive of diffuse symmetrical periventricular white matter hyperintensities. The whole exome sequencing revealed a rare homozygous missense variant in exon 4 of the LAMA2 gene on chromosome 6 (c.442C>T[p.Arg148Trp]). Adult-onset limb-girdle muscular dystrophy with white matter imaging abnormalities, hyperCKemia, and seizures should evoke suspicion of LAMA2-RD. This case brings forth an ultra-rare genetic mutation that has not been previously reported in individuals of South Asian ethnicity leading to LAMA2-RD. More cases of late-onset LAMA2-RD from various ethnicities need to be reported to expand our understanding of the clinical-genetic spectrum of the disease.

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Background: Laminin-α2 (LAMA2) chain-deficient muscular dystrophy (LAMA2-MD) is the most common congenital muscular dystrophy (CMD) in the world. Its main manifestations are muscle weakness and hypotonia that occur after birth or at early infancy. Case Description: We reported a case of a 3-year-old and 6-month-old boy presented with delayed motor development, elevated creatine kinase (CK) levels, and abnormal white matter in the brain. Whole exome sequencing (WES) showed compound heterozygous variants of the LAMA2 gene. This case reports for the first time the compound heterozygous LAMA2 variants c.5476C>T (p.R1826*) (paternal inheritance) with c.2749 + 2dup (maternal inheritance), as both variants are interpreted as pathogenic/potentially pathogenic variants. Conclusions: This study reports a novel heterozygous variant, including two pathogenic variants in the LAMA2 gene, and highlights the effectiveness of highly efficient exome sequencing applying in patients with undefined CMDs.

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Lamanema chavezi is an entero-hepatic strongylid parasite specific to South American camelids. It has been reported only on few occasions outside South America. Due to its hepatic migration, it can cause extensive liver damage, leading to granulomatous and fibrotic hepatitis and manifesting with lethargy, anorexia, and even death. We are reporting the second case of L. chavezi infection in Europe and the first in Switzerland. The patient was a three-year old neutered male llama (Lama glama). Clinical examination revealed bloody mucous discharge from the anus. Fecal sedimentation/flotation revealed strongylid eggs consistent with L. chavezi, which were molecularly confirmed by a PCR targeting the ITS2 plus 5.8S and 28S rDNA flanking regions and amplicon sequencing. Eighteen weeks after administration of a single dose of eprinomectin (0.2 mg/kg i.m.), no further L. chavezi eggs were detected in the feces. The source of infection could not be traced back. The entire herd consisted of llamas bred in Switzerland. L. chavezi has been rarely reported outside South America, but its potential for pathogenicity and establishment should not be underestimated. Fecal sedimentation/flotation techniques should be routinely performed to ensure early detection of the parasite.

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LAMA2-related muscular dystrophies (LAMA2-RDs) constitute the most prevalent subtype of congenital muscular dystrophies (CMDs). The clinical spectrum of LAMA2-RDs exhibits considerable diversity, particularly in motor development and disease progression. Phenotypic variability ranges from severe, early-onset presentation, known as merosin-deficient CMD type 1A, to milder, late-onset presentations, including limb-girdle muscular dystrophy-like phenotype. In this study, whole exome sequencing (WES) was applied to a family with a single proband affected by severe muscular dystrophy. The identified causative mutation was a biallelic splice-site mutation in intron 58 of the LAMA2 gene, leading to a premature termination codon in the critical G domain of laminin-α2 and resulting in a severe phenotype. Additionally, we summarized previously reported splice-site mutations to investigate the clinical and transcription consequences of these mutations. Our findings conclude that splice-site mutations predominantly lead to severe MDC1A, whether in a homozygous or heterozygous state, often associated with another loss-of-function mutation. Besides, splice-site mutations with available analysis of their transcriptional consequences were found to be responsible for exon skipping in most cases and the loss of the reading frame. These findings revealed the importance of WES in identifying disease-causing mutations, particularly in highly diversified pathologies like LAMA2-RDs. The results also underscore the importance of transcriptional analysis in determining the impact of splice-site mutations and the phenotype of LAMA2-RDs on patients.

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Background: Uncover the pivotal link between lymphocyte-specific protein tyrosine kinase (Lck)-related genes and clinical risk stratification in pancreatic cancer. Methods: This study identifies shared genes between differentially expressed genes (DEGs) and Lck-related genes in pancreatic cancer using a methodological framework rooted in The Cancer Genome Atlas database. Feature gene selection is accomplished and a signature model is constructed. Statistical significant clinical endpoints such as overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were defined. Results: After performing random survival forest, Lasso regression, and multivariate Cox regression model, 7 trait genes out of 272 Lck-associated DEGs are selected to create a signature model that is independent of other clinical factors and can predict OS and DSS. It appears that high-risk patients have activated the TP53 signaling pathway and the cell cycle signaling pathway. LAMA3 turned out to be the hub gene of the signature with high expression in pancreatic cancer. Patients with increased expression of LAMA3 had a short OS, DSS, and PFI in comparison. The candidate competing endogenous RNA network of LAMA3 turned out to be OPI5-AS1/hsa-miR-186-5p/LAMA3 axis. Conclusions: A characteristic signature of seven Lck-related genes, especially LAMA3, has been shown to be a key factor in clinical risk stratification for pancreatic cancer.

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Background: Chronic obstructive pulmonary disease (COPD) is a preventable, progressive disease and the third leading cause of death worldwide. The epidemiological data of COPD from Gulf countries are very limited, as it remains underdiagnosed and underestimated. Risk factors for COPD include tobacco cigarette smoking, water pipe smoking (Shisha), exposure to air pollutants, occupational dusts, fumes, and chemicals. Inadequate treatment of COPD leads to worsening of disease. The 2024 GOLD guidelines recommend use of inhaled bronchodilators, corticosteroids, and adjunct therapies for treatment and management of COPD patients based on an individual assessment of the severity of symptoms and risk of exacerbations. This article reviews COPD pharmacotherapy in the Gulf countries and explores the role of nebulization in the management of COPD in this region. Methods: To review the COPD pharmacotherapy in the Gulf Countries, literature search was conducted using PubMed, Medline, Cochrane Systematic Reviews, and Google Scholar databases (before December 2022), using search terms such as COPD, nebulization, inhalers/inhalation, aerosols, and Gulf countries. Relevant articles from the reference list of identified studies were reviewed. Consensus statements, expert opinion, and other published review articles were included. Results: In the Gulf countries, pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers, and nebulizers are used for drug delivery to COPD patients. pMDIs and DPIs are most prone to errors in technique and other common device handling errors. Nebulization is another mode of inhalation drug delivery, which is beneficial in certain patient populations such as the elderly and patients with cognitive impairment, motor or neuromuscular disorders, and other comorbidities. Conclusion: There is no major difference between Gulf countries and rest of the world in the approach to management of COPD. Nebulizers should be considered for patients who have difficulties in accessing or using MDIs and DPIs, irrespective of geographical location.

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LAMA2-related congenital muscular dystrophy (LAMA2-CMD), characterized by laminin-α2 deficiency, is debilitating and ultimately fatal. To date, no effective therapy has been clinically available. Laminin-α1, which shares significant similarities with laminin-α2, has been proven as a viable compensatory modifier. To evaluate its clinical applicability, we establish a Lama2 exon-3 deletion mouse model (dyH/dyH). The dyH/dyH mice exhibit early lethality and typical LAMA2-CMD phenotypes, allowing the evaluation of various endpoints. In dyH/dyH mice treated with synergistic activation mediator-based CRISPRa-mediated Lama1 upregulation, a nearly doubled median survival is observed, as well as improvements in weight and grip. Significant therapeutical effects are revealed by MRI, serum biochemical indices, and muscle pathology studies. Treating LAMA2-CMD with LAMA1 upregulation is feasible and that early intervention can alleviate symptoms and extend lifespan. Additionally, we reveal limitations of LAMA1 upregulation, including high-dose mortality and non-sustained expression, which require further optimization in future studies.

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BACKGROUND: Real-world data assessing characteristics of patients with asthma initiating inhaled corticosteroid/long-acting muscarinic antagonist/long-acting ß2-agonist (ICS/LAMA/LABA) triple therapy in Japan are limited. METHODS: Descriptive, observational study of patients with asthma aged ≥15 years newly initiating single- or multiple-inhaler triple therapy (SITT: fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI], SITT: indacaterol/glycopyrronium bromide/mometasone furoate [IND/GLY/MF] or MITT) or ICS/LABA using JMDC/Medical Data Vision (MDV) health insurance databases from February 2021-February 2022 (first prescription date: index date). Patients were assigned to three non-mutually exclusive cohorts: A) new FF/UMEC/VI initiators; B) new FF/UMEC/VI, IND/GLY/MF, or MITT initiators; C) new FF/UMEC/VI, IND/GLY/MF, MITT or ICS/LABA initiators as initial maintenance therapy (IMT). Patient characteristics were assessed descriptively for 12-months pre-treatment initiation (baseline period). RESULTS: Cohort A: among new FF/UMEC/VI initiators, 12.8% and 0.1% (JMDC) and 21.7% and 0.9% (MDV) of patients had ≥1 moderate and severe exacerbation; 52.0% (JMDC) and 79.2% (MDV) had ICS/LABA use. Cohort B: most patients initiated FF/UMEC/VI and IND/GLY/MF over MITT (JMDC: 91.3% vs 8.7%; MDV: 67.8% vs 32.2%), with fewer exacerbations and lower rescue medication use. Cohort C: a greater proportion of FF/UMEC/VI initiators as IMT experienced a moderate exacerbation at index versus ICS/LABA initiators as IMT (JMDC: 17.8% vs 10.7%; MDV: 8.0% vs 5.1%). CONCLUSIONS: Patient characteristics were generally similar between treatment groups; SITT initiators had fewer exacerbations and lower rescue medication use than MITT initiators, represented by the greater proportion of IMT among SITT versus MITT initiators. Physicians may have prescribed triple over dual therapy as IMT in response to an exacerbation.

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BACKGROUND: We report a rare case of primary clinical presentation featuring elevated creatine kinase (CK) levels in a neonate, which is associated with the LAMA2 gene. In this case, a heterozygous mutation in exon5 of the LAMA2 gene, c.715C>G (resulting in a change of nucleotide number 715 in the coding region from cytosine to guanine), induced an amino acid alteration p.R239G (No. 239) in the patient, representing a missense mutation. This observation may be elucidated by the neonatal creatine monitoring mechanism, a phenomenon not previously reported. CASE SUMMARY: We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment. The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d. Admission occurred at 18 d of age, and despite prolonged treatment with creatine and vitamin C, the elevated CK levels showed limited improvement. Whole exome sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn, correlating with a clinical phenotype. However, the available information offers insufficient evidence for clinical pathogenicity. CONCLUSION: Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels, for which no specific treatment exists. Whole genome sequencing facilitates early diagnosis.

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INTRODUCTION: Long-acting muscarinic antagonists (LAMA) or beta-2 agonists (LABA) have been recommended for symptom control in group A COPD patients as a first-line bronchodilator treatment in GOLD guidelines. However, there is no mention of priority/superiority between the two treatment options. We aimed to compare the effectiveness of these treatments in this group. METHODS: The study cohort was formed of all subjects from six pulmonology clinics with an initial diagnosis of COPD who were new users of a LAMA or LABA from January 2020 to December 2021. Seventy-six group A COPD patients, in whom LABA or LAMA therapy had been started in the last 1 month as a first-line treatment, were included in our study. Participants were evaluated with spirometry, COPD Assessment Test (CAT), mMRC scale, and St. George Respiratory Questionnaire (SGRQ) for three times (baseline, 6-12th months). RESULTS: There were 76 group A COPD patients with LAMA (67.1%) and LABA (32.9%). The number of patients who improved in CAT score at the end of the first year was significantly higher in patients using LAMA than those using LABA (p = 0.022); the improvement at minimum clinically important difference (MCID) in CAT score of LAMA group at 1st year was also significant (p = 0.044). SGRQ total and impact scores were found to be statistically lower at 1st year compared to baseline in patients using LAMA (p = 0.010 and 0.006, respectively). Significant improvement was detected in CAT and SGRQ scores at the 6th month visit in the LAMA group having emphysema (p = 0.032 and 0.002, respectively). CONCLUSION: According to significant improvements in CAT and SGRQ score, LAMA may be preferred over LABA as a bronchodilator agent in group A COPD patients, especially in emphysema-dominant phenotype.

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