Introduction: Histoplasmosis is a rare opportunistic, inhalation-acquired systemic mycosis caused by Histoplasma capsulatum, endemic to Southeast Asia, including Malaysia. Although classically seen in immunocompromised hosts, it is increasingly reported in immunocompetent individuals. Infection is associated with environmental exposures such as bat or bird droppings and soil disruption. Histoplasmosis is a progressive granulomatous disease that can closely mimic tuberculosis and malignancy, making diagnosis challenging. Case: An 87-year-old Malay male with a history of treated pulmonary tuberculosis presented with a 6-month history of intermittent fever, anorexia, weight loss, and hypotension. Initial computed tomography imaging demonstrated bilateral heterogeneous adrenal masses (right: 2.2 × 3.7 × 5.0 cm; left: 2.0 × 3.7 × 5.2 cm) with indeterminate washout characteristics. Biochemical adrenal evaluation, including a short Synacthen test, confirmed primary adrenal insufficiency. Extensive microbiological and malignancy workup, including bronchoscopy, cultures, and tumor markers, was non-diagnostic. In view of clinical deterioration and epidemiological risk, empirical antituberculous therapy was initiated; however, no clinical improvement was observed after 2 months. PET-FDG revealed intensely hypermetabolic bilateral adrenal masses (SUVmax right 16.7, left 13.2) with no other abnormal foci. Non-invasive fungal investigations were negative. Definitive diagnosis was established via computed tomography-guided adrenal biopsy, which demonstrated necrotizing granulomatous inflammation with intracellular yeasts, subsequently identified as H. capsulatum. The patient was treated with oral itraconazole and corticosteroid replacement, resulting in significant clinical improvement and planned interval radiological reassessment. Conclusion Disseminated histoplasmosis is a diagnostic challenge, particularly in frail elderly patients, where invasive procedures may be delayed. It can mimic tuberculosis and malignancy and may lack an identifiable exposure history. Non-invasive tests may be inconclusive, making tissue biopsy essential. Adrenal involvement may result in primary adrenal insufficiency, further complicating the clinical picture. Early consideration and timely confirmation are crucial for appropriate management.
Adrenal incidentaloma ; Lung Neoplasms

Introduction: Hashimoto's thyroiditis is a common autoimmune thyroid disease; however, pulmonary involvement is a rare manifestation. Lymphocytic interstitial pneumonitis is commonly associated with autoimmune diseases, but its association with Hashimoto's thyroiditis remains poorly understood. Case: A 63-year-old male with prior diagnosis of Hashimoto's thyroiditis presented with recurrent massive pleural effusion and progressive dyspnea. He also experienced fatigue, cold intolerance, and constipation. Physical examination revealed facial puffiness, diffuse goiter, and dry skin. Thyroid function tests performed 6 months before admission confirmed overt hypothyroidism (thyroidstimulating hormone [TSH] 80.30 µIU/mL, free thyroxine 4 [FT4] 0.46 ng/dL). One month prior to admission, laboratory findings showed subclinical hypothyroidism (TSH 9.09 µIU/mL, FT4 1.42 ng/dL). Despite levothyroxine treatment TSH levels remained elevated at 21.8 µIU/mL during admission. Anti-thyroid peroxidase antibodies were positive (13.95 IU/mL). Repeated thoracentesis revealed exudative pleural effusion with lymphocytic predominance and no evidence of malignancy in cytological examination. Infectious etiologies and malignancy were ruled out. Thyroid ultrasonography demonstrated diffuse hypoechoic enlargement of the thyroid gland. Chest radiography showed massive unilateral pleural effusion, while thoracic computed tomography revealed ground-glass opacities with a reticulogranular pattern and interlobular septal thickening, accompanied by multiple thin-walled cysts, highly suggestive of lymphocytic interstitial pneumonitis. Thyroid immunohistochemical analysis was performed (CD 20, CD 3, CD 10, CD 138, Ki 67, BCL 2, BCL 6, Thyroglobulin, MUM 1, Cyclin D1), consistent with lymphocytic thyroiditis. Significant clinical and laboratory improvement was achieved after combined treatment with levothyroxine and corticosteroid. Conclusion This case underscores the importance of considering autoimmune-related lymphocytic interstitial pneumonitis in patients with Hashimoto's thyroiditis who present with unexplained recurrent pleural effusion after exclusion of more common etiologies, such as infection and malignancy. Early recognition may lead to favorable improvement.
Lung Diseases, Interstitial ; Pleural Effusion ; Thyroiditis

BACKGROUND

Bronchial asthma is one of the most common chronic childhood diseases encountered in the primary care setting. Adherence to recommendations from clinical practice guidelines on asthma can be utilized as an indicator of quality of care when evaluating the implementation of the universal health care in the Philippines.

To determine the clinical profile of pediatric patients with bronchial asthma; and to evaluate the prescription patterns for asthma treatment in a primary care setting.

This was a retrospective cohort study that involved review of the electronic medical records in a rural site of the Philippine Primary Care Studies (PPCS). All patients less than 19 years old who were diagnosed with asthma from April 2019 to March 2021 were included. Quality indicators for asthma care were based on adherence to recommendations from the 2019 Global Initiative for Asthma (GINA) Guidelines.

This study included 240 asthmatic children with mean age of 6 years (SD ± 4.9) and a slight male preponderance (55.4%). Majority (138 children or 57.5%) were less than 6 years old. Out of the 240 children, 224 (93.3%) were prescribed inhaled short-acting beta-agonists (SABA) and 66 (27.5%) were prescribed oral SABA. Only 14 children (5.8%) were prescribed inhaled corticosteroids (ICS), with 13 children (5.4%) given ICS with longacting beta-agonists (LABA) preparations, and one child (0.4%) given ICS alone. Quality indicators used in this study revealed underutilization of ICS treatment across all age groups, and an overuse of SABA-only treatment in children 6 years old and above. Moreover, 71.3% of the total patients were prescribed antibiotics despite the current GINA recommendation of prescribing antibiotics only for patients with strong evidence of lung infection, such as fever or radiographic evidence of pneumonia.

There were 240 children diagnosed with asthma over a 2-year period in a rural community, with a mean age of 6 years old and a slight male predominance. This quality-of-care study noted suboptimal adherence of rural health physicians to the treatment recommendations of the GINA guidelines, with overuse of SABA and underuse of ICS for asthma control.

BACKGROUND AND OBJECTIVES

Cell lines serve as invaluable tools in studying lung cancer biology and developing new therapies to combat the disease. However, commercially available cell lines are typically of Caucasian origin and may be less representative of the local genetic background. To address this, our lab previously immortalized cells from pleural fluid of a Filipino non-small cell lung cancer (NSCLC) patient via CDK4 transduction. Copy number variations (CNVs) are a type of genetic variation which may affect physiology and disease by disrupting gene function or altering gene expression, and in cancer, these may be associated with patient outcomes. CNV profiling can be valuable for understanding the biology of our immortalized cells and identifying genes that could serve as potential targets for diagnostic, prognostic, and therapeutic interventions. This study aimed to characterize previously immortalized NSCLC-derived cells, GL01, in comparison with an established lung adenocarcinoma (LUAD) cell line, A549, through whole-genome microarray-based copy number profiling.

DNA was extracted from GL01 and A549 cells using a commercially-available silica-based DNA extraction kit. DNA extracts were quantified and normalized for microarray analysis. Whole-genome copy number profiling was done using the OncoScan CNV Plus Assay following the manufacturer’s protocols, and data was analyzed using the Chromosome Analysis Suite software. Functional analysis of genes identified to be involved in copy number aberrations was done using the PANTHER Classification System.

Copy number aberrations span 1,592,737,105 bp in GL01 and 1,715,708,552 bp in A549, with a high degree of concordance between the two. Large-scale and focal copy number aberrations previously identified to be recurrent in various LUAD cohorts were present in both GL01 and A549. Focal copy number aberrations associated with previously described lung cancer-related genes involve the PDE4D gene in GL01 and the SKIL and CDKN2A/CDKN2B genes in both GL01 and A549. PANTHER Pathway analysis of genes positively correlated with mRNA expression showed that the ubiquitin proteasome pathway was significantly overrepresented in both GL01 (FDR p = 0.000074) and A549 (FDR p = 0.000075), with 20 genes involved. Additionally, the KRAS:p.G12C/S:c.34G>T/A somatic mutation variant was detected in both GL01 and A549.

This study provides a method for identifying potentially clinically-relevant genes associated with a sample’s copy number aberrations and the pathways they represent, providing personalized mechanistic, prognostic, and therapeutic insights into the cancer biology of our cells.

BACKGROUND

COVID-19 infection poses a continuing challenge especially to those already with prior lung disease. To analyze such patients’ profile is essential in today’s health care management.

The study aimed to compare the outcomes of COVID-19 confirmed patients with and without primary lung cancer in terms of hospital stay, recovery, and mortality.

The study employed a retrospective cohort design. Chart review of all adult COVID-19 patients in Philippine General Hospital from January 2021 to June 2021 was done. A matched cohort study was conducted between COVID-19 patients with and without primary lung cancer.

Among the 953 COVID-19 patients, there were 14 patients with primary lung cancer. In terms of length of hospital stay, patients with primary lung cancer had shorter days from 1.32 to 15.1 days compared to 2.28 to 18.36 days in patients without primary lung cancer (p-value 0.271). Furthermore, they had 64% recovery rate compared to 78% in those without primary lung cancer (p-value 0.118). In terms of overall mortality rate, primary lung cancer patients had 36% rate as compared to 22% in the non-lung cancer group (p-value 0.119). Diabetes mellitus, mild to severe COVID, Remdesivir, and antibiotic use were associated with longer hospital stay while oxygen support via nasal cannula and invasive ventilation led to shorter hospital stay. Age above 50 years, chronic liver disease, other malignancy, shortness of breath, oxygen support via face mask, high flow nasal cannula, invasive ventilation, antibiotic use, hemoperfusion and nebulization showed a decrease chance of recovery while on contrary, Remdesivir showed an increase chance of recovery. An increase mortality rate was seen among age above 50 years, chronic liver disease, other malignancy, shortness of breath, oxygen support via facemask, high flow nasal cannula, invasive ventilation, antibiotics, hemoperfusion, and nebulization, in contrast to a decrease in Remdesivir therapy.

Among all admitted COVID-19 patients, primary lung cancer patients were associated with shorter hospital stay (8.21+6.89days), lower rate of recovery (64%), and higher mortality rate (36%) as compared to those without primary lung cancer. However, based on the computed p-values for each outcome, these differences are not statistically significant.

INTRODUCTION

Most cancer-related deaths globally are caused by lung cancer. The diagnosis is typically made following the evaluation of respiratory symptoms such as chronic cough or incidental finding of pulmonary lesions such as nodules and mass. Cardiac metastasis occurs in 2-18% of lung cancers, but cardiac tamponade complicating malignant pericardial effusion is an extremely rare and life-threatening initial presentation of non-small cell lung carcinoma.

A 59-year-old-male with a smoking history of 72 pack-year presented at the emergency room with severe dyspnea and was assessed to be in cardiac tamponade. The patient arrested for 16 minutes but returned to spontaneous circulation after 650mL of serosanguinous fluid was removed by pericardiocentesis. The work-up for infectious and immunologic causes was negative. Chest CT scan with contrast did not reveal any pulmonary mass. However, the pericardial fluid cytology immunohistochemical stains pointed to a primary lung adenocarcinoma. PET scan was requested which confirmed hypermetabolic focus in the left lung base. included patients admitted at East Avenue Medical Center for DFU. The primary endpoint was major amputation of the lower extremities. Data were analyzed using Receiver Operating Characteristic (ROC) analysis and logistic regression.

This case showed an extremely rare situation where life-threatening cardiac tamponade was the initial presentation of non-small cell lung adenocarcinoma, which highlights the need for vigilance in atypical presentation. Comprehensive diagnostic approach, including PET scans and cytologic analysis, must be done when standard imaging is inconclusive.

Both carcinoembryonic antigen and CA19-9 are considered as predictive markers of intestinal cancer recurrence and metastasis.In addition,CA19-9 elevation is considered as a predictive marker of connective tissue disease-related interstitial lung disease.The incidence of oxaliplatin and capecitabine-associated interstitial lung disease is low,and there is no report about CA19-9 as a predictive marker of oxaliplatin and capecitabine-associated interstitial lung disease.This paper reports a case of interstitial lung disease with CA19-9 elevation caused by oxaliplatin and capecitabine adjuvant therapy for ileocecal carcinoma.The change trend of serum carcinoembryonic antigen in this patient was consistent with tumor recurrence and metastasis,and that of serum CA19-9 was consistent with the severity of interstitial lung disease.Therefore,CA19-9 elevation after intestinal cancer surgery does not necessarily indicate the tumor recurrence and metastasis,and attention should be paid to the possibility of oxaliplatin and capecitabine-associated interstitial lung disease.
Humans ; CA-19-9 Antigen/blood* ; Capecitabine ; Cecal Neoplasms/drug therapy* ; Chemotherapy, Adjuvant ; Deoxycytidine/administration & dosage* ; Fluorouracil/administration & dosage* ; Lung Diseases, Interstitial/blood* ; Organoplatinum Compounds/administration & dosage* ; Oxaliplatin

Lung cancer is the malignancy with the highest incidence and mortality burden globally, ranking first in both morbidity and mortality among all types of malignant tumors. Pathologically, lung cancer is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for approximately 85% of cases. Due to the often subtle or nonspecific clinical manifestations in early-stage disease, many patients are diagnosed at a locally advanced or metastatic stage, where treatment options are limited and prognosis remains poor. Therefore, molecular targeted therapy focusing on driver genes has become a key strategy to improve the survival outcomes of patients with advanced NSCLC. The epidermal growth factor receptor (EGFR) is one of the most common driver genes in NSCLC. While EGFR mutations occur in approximately 12% of advanced NSCLC patients globally, the incidence rises to 55.9% in Chinese patients. Among EGFR mutations, P-loop and αC-helix compressing (PACC) mutations account for about 12.5%. Currently, EGFR tyrosine kinase inhibitors (TKIs) have become the first-line standard treatment for advanced NSCLC patients with classical EGFR mutations, with efficacy well-established through clinical studies and real-world evidence. However, with rapid advancements in NSCLC precision medicine and deeper exploration of the EGFR mutation spectrum, EGFR PACC mutations have emerged as a key clinical focus. The structural characteristics of these mutations lead to significant variability in responses to EGFR TKIs, leaving therapeutic options still limited, while detection challenges persist due to the sensitivity constraints of current testing technologies, driving increasing demand for improved diagnostic and treatment approaches. The current clinical evidence primarily stems from retrospective analyses and small-scale exploratory studies, while prospective, large-scale, high-level evidence-based medical research specifically targeting this mutation subtype remains notably insufficient. This evidence gap has consequently led to the absence of standardized guidelines or expert consensus regarding optimal treatment strategies for advanced NSCLC with EGFR PACC mutations. As a clinical consensus specifically addressing EGFR PACC-mutant NSCLC, this document provides a comprehensive framework encompassing the clinical rationale for EGFR PACC mutation testing, therapeutic strategies for advanced-stage disease, management of treatment-related adverse events, and follow-up protocols. The consensus underscores the pivotal role of EGFR PACC mutation detection in precision medicine implementation while offering evidence-based recommendations to guide personalized therapeutic decision-making. By establishing clear clinical pathways encompassing molecular testing, therapeutic intervention, and long-term monitoring for EGFR PACC-mutant NSCLC, this consensus aims to meaningfully improve patient survival outcomes while serving as a robust, evidence-based foundation for developing personalized clinical management approaches.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; ErbB Receptors/antagonists & inhibitors* ; Mutation ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/therapeutic use* ; Molecular Targeted Therapy ; Consensus

Mutations in the human epidermal growth factor receptor 2 (HER-2) gene are recognized as significant but relatively rare driver alterations in non-small cell lung cancer (NSCLC). These mutations predominantly manifest as gene mutation, amplification, and protein overexpression, with an estimated prevalence from 2.8% to 15.4% among NSCLC patients in China. Research indicates that HER-2 mutations, particularly exon 20 insertions (ex20ins), are strongly correlated with aggressive tumor biology, poor prognosis, and limited responsiveness to immunotherapy, thereby exhibiting characteristics of "cold tumors". Overexpression and amplification of HER-2 are also indicative of a heightened risk of chemotherapy resistance and unfavorable survival outcomes, suggesting a distinct molecular subtype with unique biological behaviors. In recent years, novel antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), have demonstrated groundbreaking efficacy in HER-2-mutant advanced NSCLC patients. These ADCs have shown significant clinical benefits, including high objective response rates and progression-free survival advantages, making T-DXd the first targeted therapy approved for this patient population globally. Additionally, ADCs have exhibited therapeutic potential in patients with HER-2 overexpression, thus broadening the scope of their indications. To standardize the clinical diagnosis and treatment of HER-2 variant NSCLC, the Chinese Anti-cancer Association convened multidisciplinary experts from oncology, pulmonology, thoracic surgery, pathology, and molecular diagnostics to develop this consensus based on the latest evidences from both domestic and international studies, coupled with China's clinical practice experience. This consensus focuses on the molecular characteristics, clinical significance, diagnostic strategies, treatment options, and safety management of HER-2 alterations, addressing ten critical clinical questions in a systematic manner. It is recommended that HER-2 status be routinely tested at initial diagnosis, disease progression, or recurrence in NSCLC. Mutation detection should prioritize next-generation sequencing (NGS), while protein overexpression may be assessed using immunohistochemistry (IHC) standards for gastric cancer. Fluorescence in situ hybridization (FISH) is recommended for detecting HER-2 amplification. Regarding treatment, for HER-2-mutant patients, first-line therapy may involve chemotherapy with or without immune checkpoint inhibitors (ICIs), similar to treatment approaches for driver-gene negative populations. Upon failure of first-line treatment, trastuzumab deruxtecan, may be considered as alternative therapeutic options. For patients with HER-2 overexpression, ADCs should be considered after failure of standard systemic therapy. However, the management of HER-2 amplification remains insufficiently supported by evidence, necessitating a cautious, individualized approach. The consensus also includes detailed recommendations for screening and managing adverse effects associated with ADCs, such as interstitial lung disease (ILD), emphasizing the crucial role of safety management in ensuring treatment efficacy. The publication of this consensus aims to drive the standardization of molecular diagnosis and treatment pathways for HER-2 variant NSCLC, improve clinical outcomes and quality of life for patients, and facilitate the implementation of personalized precision treatment strategies.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Receptor, ErbB-2/metabolism* ; Mutation ; Immunoconjugates/therapeutic use* ; Consensus ; Trastuzumab/therapeutic use* ; Camptothecin/analogs & derivatives*

OBJECTIVE: To observe the skin surface temperature at the related back-shu points in the patients with the different levels of pulmonary ventilation function in chronic persistent asthma, and to explore the correlation between the skin temperature at the back-shu points and pulmonary ventilation function indexes based on "lung governing the skin and hair". METHODS: Sixty-one patients with chronic persistent asthma, based on the level of pulmonary ventilation function, were assigned into a reduced pulmonary ventilation function group (reduced function group, 32 cases) and a normal pulmonary ventilation function group (normal function group, 29 cases). In the two groups, the skin surface temperature was measured in the sites of bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23); and the pulmonary ventilation function indexes (the percentage of predicted value of forced vital capacity [FVC%pred], the percentage of predicted value of forced expiratory volume in the first second [FEV1%pred], the percentage of predicted value of FEV1/FVC [FEV1/FVC%pred] and the percentage of predicted value of the peak expiratory flow [PEF%pred]) were recorded. The correlation between the skin surface temperature of acupoints and pulmonary ventilation function was analyzed. RESULTS: Compared with the normal function group, the surface skin temperature at the bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23) was higher in the reduced function group (P<0.05, P<0.01). Compared with the normal function group, FEV1%pred, FEV1/FVC%pred and PEF%pred were decreased in the reduced function group (P<0.001). There was no significant difference in FVC%pred between the two groups (P>0.05). The skin surface temperature at the bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23) was negatively correlated with FVC%pred, FEV1%pred, FEV1/FVC%pred and PEF%pred in 61 patients with chronic persistent asthma (P<0.001, P<0.01, P<0.05). CONCLUSION The skin surface temperature at back-shu points is elevated in line with the the decline of pulmonary ventilation function in the patients with chronic persistent asthma, presenting a negative correlation with pulmonary ventilation function indexes. It is preliminarily verified that back-shu point is characterized by reflecting the visceral disorders.
Humans ; Female ; Male ; Asthma/therapy* ; Middle Aged ; Adult ; Skin Temperature ; Lung/physiopathology* ; Acupuncture Points ; Pulmonary Ventilation ; Aged ; Chronic Disease/therapy* ; Young Adult ; Hair