1.A Hidden Diagnosis: Disseminated Histoplasmosis Mimicking Tuberculosis in the Elderly
Wan Muhamad Amir Wan Md Zin ; Moon Yan Yap ; Meroshini Sundaran ; Siti Nabilah &lsquo ; Atiqah Othman ; Siti Nabihah Mohamed Hatta ; Maz Anirah Abdul Azis
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):28-
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
2.Hashimoto's Thyroiditis Presenting With Recurrent Massive Pleural Effusion Suggestive of Lymphocytic Interstitial Pneumonitis
Endah Pratamaningtias ; Nyoman Satvika Dharma Yudha
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):106-
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
3.Molecular mechanisms of lung cancer induced by the insecticide lambda-cyhalothrin.
Yongshun DUAN ; Zifei WANG ; Mengxuan WU ; Shuo WANG ; Xin GUO ; Zhihua NI
Chinese Journal of Biotechnology 2025;41(10):3801-3816
The inappropriate utilisation of the agricultural insecticide lambda-cyhalothrin (LCT) has the potential to result in residues that compromise food safety and human health. Respiratory exposure represents a major route of LCT contact in humans. Nevertheless, its deleterious effects on the respiratory system remain inadequately characterized. It is imperative to elucidate the potential relationship and mechanisms by which lung cancer, a significant malignant neoplasm of the respiratory system, is associated with exposure to LCT. The objective of this study is to utilise bioinformatics methodologies to screen and analyse the key target molecules affected by LCT in the occurrence of lung cancer, and their mechanisms of action. Specifically, network toxicology methods were employed to identify core targets of LCT-induced lung cancer. Subsequently, functional annotation to delineate associated cellular pathways, and finally, molecular docking to simulate binding modes between LCT and shared core targets. Core target screening identified 50 targets for large cell lung cancer, 54 for small cell lung cancer, 29 for lung squamous cell carcinoma, and 28 for lung adenocarcinoma, with EGFR, HSP90AA1, JUN, CCL2, MYC, CXCL8, and HSPA4 shared in all subtypes. Functional annotation revealed that LCT-triggered oncogenic pathways predominantly involved ubiquitination, chemotaxis, and tumor immune signaling. Molecular docking demonstrated spontaneous binding of LCT to core targets mediated by hydrogen bonds and π-cation interactions. These results establish a theoretical framework for evaluating LCT-associated risks of lung cancer and respiratory system damage.
Lung Neoplasms/metabolism*
;
Pyrethrins/toxicity*
;
Humans
;
Insecticides/toxicity*
;
Nitriles/toxicity*
;
Molecular Docking Simulation
4.Thermal Ablation of Pulmonary Nodules by Electromagnetic Navigation Bronchoscopy Combined With Real-Time CT-Based 3D Fusion Navigation:Report of One Case.
Yuan XU ; Qun LIU ; Chao GUO ; Yi-Bo WANG ; Xiao-Fang WU ; Chen-Xi MA ; Gui-Ge WANG ; Qian-Shu LIU ; Nai-Xin LIANG ; Shan-Qing LI
Acta Academiae Medicinae Sinicae 2025;47(1):137-141
A nodule in the right middle lobe of the lung was treated by a combination of cone-beam CT,three-dimensional registration for fusion imaging,and electromagnetic navigation bronchoscopy-guided thermal ablation.The procedure lasted for 90 min,with no significant bleeding observed under the bronchoscope.The total radiation dose during the operation was 384 mGy.The patient recovered well postoperatively,with only a small amount of blood in the sputum and no pneumothorax or other complications.A follow-up chest CT on the first day post operation showed that the ablation area completely covered the lesion,and the patient was discharged successfully.
Humans
;
Bronchoscopy/methods*
;
Catheter Ablation/methods*
;
Cone-Beam Computed Tomography
;
Electromagnetic Phenomena
;
Imaging, Three-Dimensional
;
Lung Neoplasms/diagnostic imaging*
;
Tomography, X-Ray Computed
5.Endobronchial Metastasis From Rectal Cancer Treated by High-Frequency Electrocautery Ablation via Bronchoscope and Targeted Drugs:Report of One Case.
Jian-Hua YUAN ; Zong-Zhou XIE ; Y U WEI-LING ; Rong-Hua CUI ; L I JIAN-WANG
Acta Academiae Medicinae Sinicae 2025;47(1):142-145
The lungs are the most common sites of metastases from non-pulmonarymalignancies. Endobronchial metastases are rare and have no specificity in clinical manifestations,thus being prone to misdiagnosis and delayed treatment.The common tumors associated with endobronchial metastasis are renal,breast,and colorectal cancers.This article reported one case of postoperative rectal cancer with endobronchial and lung metastases,which was relieved by high-frequency electrocautery ablation via bronchoscope,chemotherapy,and targeted drugs,aiming to provide a reference for clinical diagnosis and treatment.
Humans
;
Rectal Neoplasms/pathology*
;
Electrocoagulation/methods*
;
Bronchial Neoplasms/drug therapy*
;
Bronchoscopy
;
Lung Neoplasms/secondary*
;
Bronchoscopes
6.Interstitial Lung Disease With CA19-9 Elevation After Oxaliplatin and Capecitabine Adjuvant Therapy for Ileocecal Carcinoma:Report of One Case.
Wen-Jing YANG ; Guo-Wang YANG ; Ying LI ; Hao WANG ; Lin YANG ; Wei-Ru XU
Acta Academiae Medicinae Sinicae 2025;47(4):660-665
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
7.Comparison of treatment regimens for unresectable stage III epidermal growth factor receptor ( EGFR ) mutant non-small cell lung cancer.
Xin DAI ; Qian XU ; Lei SHENG ; Xue ZHANG ; Miao HUANG ; Song LI ; Kai HUANG ; Jiahui CHU ; Jian WANG ; Jisheng LI ; Yanguo LIU ; Jianyuan ZHOU ; Shulun NIE ; Lian LIU
Chinese Medical Journal 2025;138(14):1687-1695
BACKGROUND:
Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen.
METHODS:
We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints.
RESULTS:
A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis.
CONCLUSIONS:
For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy.
REGISTRATION
PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans
;
Carcinoma, Non-Small-Cell Lung/therapy*
;
ErbB Receptors/genetics*
;
Lung Neoplasms/drug therapy*
;
Mutation/genetics*
;
Protein Kinase Inhibitors/therapeutic use*
;
Chemoradiotherapy
;
Antibodies, Monoclonal/therapeutic use*
8.Development and multicenter validation of machine learning models for predicting postoperative pulmonary complications after neurosurgery.
Ming XU ; Wenhao ZHU ; Siyu HOU ; Hongzhi XU ; Jingwen XIA ; Liyu LIN ; Hao FU ; Mingyu YOU ; Jiafeng WANG ; Zhi XIE ; Xiaohong WEN ; Yingwei WANG
Chinese Medical Journal 2025;138(17):2170-2179
BACKGROUND:
Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery.
METHODS:
PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed.
RESULTS:
PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model.
CONCLUSIONS:
The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes.
TRIAL REGISTRATION
ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult
;
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
Algorithms
;
Lung Diseases/etiology*
;
Machine Learning
;
Neurosurgical Procedures/adverse effects*
;
Postoperative Complications/diagnosis*
;
Risk Factors
;
ROC Curve
9.Real-world long-term outcomes of non-small cell lung cancer patients undergoing neoadjuvant treatment with or without immune checkpoint inhibitors.
Bolun ZHOU ; Lin LI ; Fan ZHANG ; Qilin HUAI ; Liang ZHAO ; Fengwei TAN ; Qi XUE ; Wei GUO ; Shugeng GAO
Chinese Medical Journal 2025;138(22):2963-2973
BACKGROUND:
Immune checkpoint inhibitors (ICIs) have been included in various neoadjuvant therapy (NAT) regimens for non-small cell lung cancer (NSCLC). However, due to the relatively short period for the use of ICIs in NAT, patients' clinical outcomes with different regimens are uncertain. Our study aims to examine the efficacy of neoadjuvant immunotherapy (NAIT) for NSCLC patients and compare the overall survival (OS) and event-free survival (EFS) of patients receiving different NAT regimens.
METHODS:
This study retrospectively included 308 NSCLC patients treated with different NAT regimens and subsequent surgery in National Cancer Center between August 1, 2016 and July 31, 2022. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the prognosis of patients.
RESULTS:
With a median follow-up of 27.5 months, the 1-year OS rates were 98.8% and 96.2%, and the 2-year OS rates were 96.6% and 85.8% in patients of the NAIT and neoadjuvant chemotherapy (NACT) group, respectively (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.160-0.720; P = 0.003). The 1-year EFS rates were 96.0% and 88.0%, and the 2-year EFS rates were 92.0% and 77.7% for patients in the NAIT and NACT groups, respectively (HR, 0.438; 95% CI, 0.276-0.846; P = 0.010). For patients who did not achieve pathological complete response (pCR), significantly longer OS ( P = 0.012) and EFS ( P = 0.019) were observed in patients receiving NAIT than those receiving NACT. Different NAT regimens had little effect on surgery and the postoperative length of stay (6 [4, 7] days vs . 6 [4, 7] days, Z = -0.227, P = 0.820).
CONCLUSIONS
NAIT exhibited superior efficacy to NACT for NSCLC, resulting in longer OS and EFS. The OS and EFS benefits were also observed among patients in the NAIT group who did not achieve pCR.
Humans
;
Carcinoma, Non-Small-Cell Lung/mortality*
;
Male
;
Female
;
Lung Neoplasms/mortality*
;
Middle Aged
;
Immune Checkpoint Inhibitors/therapeutic use*
;
Neoadjuvant Therapy/methods*
;
Retrospective Studies
;
Aged
;
Adult
;
Kaplan-Meier Estimate
;
Treatment Outcome
;
Immunotherapy/methods*
10.Clinical practice guidelines for perioperative multimodality treatment of non-small cell lung cancer.
Wenjie JIAO ; Liang ZHAO ; Jiandong MEI ; Jia ZHONG ; Yongfeng YU ; Nan BI ; Lan ZHANG ; Lvhua WANG ; Xiaolong FU ; Jie WANG ; Shun LU ; Lunxu LIU ; Shugeng GAO
Chinese Medical Journal 2025;138(21):2702-2721
BACKGROUND:
Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment.
METHODS:
The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process.
RESULTS:
The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC.
CONCLUSIONS
This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans
;
Carcinoma, Non-Small-Cell Lung/therapy*
;
Lung Neoplasms/therapy*
;
Combined Modality Therapy
;
Perioperative Care


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