Search Results (3,348)

One characteristic of tumor cells is the increased anaerobic metabolism through glycolysis leading to an acidic environment of the tumor. This acidity is linked to tumor progression, invasion and metastasis, besides stimulated survival pathways in the malignant cells. The aim of our analysis is to investigate the role of systemic acid–base parameters such as the pH, bicarbonate, baseexcess and lactate in lung cancer patients. Furthermore, alterations in electrolytes and hemoglobin were investigated regarding their impact on overall survival. Data of 937 non-small-cell lung cancer (NSCLC) patients, who underwent anatomic video-assisted thoracoscopic surgery (VATS) resection, was collected in a prospectively maintained database and analyzed. To minimize confounding effects and due to the retrospective study design, we decided to use data from the first arterial blood gas analysis during surgery and the most recent lab results prior to surgery. We found significant correlations between low systemic bicarbonate (<20 mEq/L) and overall survival (p = 0.006). Hyponatremia (<135 mmol/L) correlated with lower 5-year overall survival (p = 0.004) and decreased disease-free survival (p = 0.017). Hypochloremia (<98 mmol/L) was linked to reduced overall survival (p = 0.003) and hypocalcemia (<1.15 mmol/L) with worse disease-free survival (p = 0.015). Hemoglobin under 12 g/dL for women and 13 g/dL for men was associated with poorer outcomes (p < 0.001). Other acid–base parameters such as the pH (p = 0.563), baseexcess (BE) (p = 0.290) and lactate (p = 0.527) did not show significant differences in overall or disease-free (pH: p = 0.130; BE: p = 0.148; lactate: p = 0.418) survival. Systemic bicarbonate, sodium, calcium, chloride and hemoglobin levels were found as prognostic markers and possible therapeutic targets to improve overall survival. Further investigations are necessary to develop therapeutic strategies. Full article

Background/Objectives: The application of additive manufacturing in medicine, and specifically in personalised medicine, has achieved notable development. This article aims to present the results and benefits of applying a comprehensive methodology to simulate, plan, and manufacture customised three-dimensional medical prosthetic devices for use in surgery to restore bone structures with congenital and acquired malformations. Methods: To digitally reconstruct a bone structure in three dimensions from a medical image, a segmentation process is developed to correlate the anatomical model. Then, this model is filtered using a post-processing step to generate stereolithography (STL) files, which are rendered using specialised software. The segmentation of tomographic images is achieved by the specific intensity selection, facilitating the analysis of compact and soft tissues within the anatomical region of interest. With the help of a thresholding algorithm, a three-dimensional digital model of the anatomical structure is obtained, ready for printing the required structure. Results: The described cases demonstrate that the use of anatomical test models, cutting guides, and customised prostheses reduces surgical time and hospital stay, and achieves better aesthetic and functional results. Using materials such as polylactic acid (PLA) for presurgical models, appropriate resins for cutting guides, and biocompatible materials such as polyether ether ketone (PEEK) or polymethylmethacrylate (PMMA) for prostheses, the described improvements are achieved. Conclusions: The achievements attained demonstrate the feasibility of applying these techniques, their advantages and their accessibility in Ecuador. They also reinforce the ideas of personalised medicine in the search for medical treatments and procedures tailored to the needs of each patient. Full article

Perioperative/neoadjuvant chemo-immunotherapy is a standard treatment for patients with resectable non-small cell lung cancer (NSCLC). However, several key clinical questions remain unresolved, including the monitoring of tumor response during neoadjuvant treatment, detection of residual disease after neoadjuvant treatment or after surgery, stratification of recurrence risk, and earlier detection of disease recurrence. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker to address these challenges. Data from several recent clinical trials of perioperative/neoadjuvant chemo-immunotherapy demonstrated that ctDNA clearance before surgery was associated with higher rates of major pathological response. Additionally, landmark ctDNA positivity after surgery identified patients at high risk of disease recurrence, and longitudinal ctDNA monitoring enabled earlier detection of recurrence compared with radiographic surveillance. Several ongoing trials are incorporating ctDNA as a biomarker to guide treatment decisions, including optimizing the duration of neoadjuvant therapy, evaluating the need for surgery, and tailoring adjuvant strategies. These trials, together with further development of ctDNA detection technologies, will clarify the role of ctDNA analysis in refining perioperative treatment strategies and may ultimately enable individualized care in patients with resectable NSCLC. In this review, we discuss the current research data on ctDNA analysis in NSCLC in this era of perioperative chemo-immunotherapy. Full article

Background: Pulmonary tuberculosis (TB) is increasingly recognized as a risk factor for chronic obstructive pulmonary disease (COPD), but its impact on COPD onset and severity remains poorly characterized, particularly in low- and middle-income countries. This multicenter study aimed to assess the impact of prior pulmonary TB on COPD onset, severity, the timing of the first severe exacerbation, and progression among Romanian patients with and without a history of pulmonary TB. Methods: This retrospective multicenter study included adults hospitalized for their first severe COPD exacerbation at two tertiary care centers in Romania between April 2020 and April 2025. Patients were grouped based on smoking status and prior TB history. Propensity score matching was used to control for confounding factors. Clinical characteristics, spirometry, and radiological TB patterns were analyzed comparatively between patients with prior TB and TB-naïve patients. Results: Among 403 COPD patients, those with prior TB had significantly earlier COPD onset (mean age 48.67 ± 6.42 vs. 65.61 ± 5.14 years in smokers, p < 0.001) and shorter intervals to their first severe COPD exacerbation compared to patients without prior TB (6.35 ± 4.71 vs. 15.14 ± 6.93 years in smokers, p < 0.001). COPD prevalence was higher among TB survivors compared to those without TB history, especially in smokers (OR = 5.73; 95% CI, 3.30–9.94, p < 0.001), versus non-smokers (OR =2.23; 95% CI, 1.37–3.64, p = 0.001). Radiological severity of TB lesions significantly influenced COPD prevalence among smokers (OR = 10.79, p < 0.001). Conclusions: Prior pulmonary TB substantially accelerates COPD onset, exacerbation timing, and disease severity, particularly in smokers. This multicenter comparative study demonstrates that prior pulmonary TB significantly accelerates COPD onset, exacerbation timing, and disease severity, especially among smokers. Recognizing TB history as a significant COPD risk factor underscores the importance of targeted COPD screening and tailored management in populations with high TB prevalence. Full article

Background/Objectives: Despite the significant advancements made in the diagnosis of lung cancer, the traditional diagnostic methods remain limited because they are often invasive, expensive, and not suitable for regular screening, creating a need for more accessible and non-invasive alternatives. In this context, the analysis of miRNAs in EVs and free circulating microRNA may be used as liquid biopsies in lung cancer to identify individuals at risk. This study aimed to compare miRNA profiles in the serum and EVs derived from lung cancer patients by focusing on Let-7a-5p and miR-21-3p. Materials and Methods: Serum and EVs were isolated from lung cancer patients and healthy controls. EVs were characterized using nanoparticle tracking analysis, electron microscopy, and Western blotting for surface markers (CD63, CD81, TSG101). Total miRNA levels were quantified in the serum and EVs, and specific miRNAs (hsa-let-7a-5p and hsa-miR-21-3p) were analyzed using RT-qPCR. Statistical analysis evaluated miRNA expression across clinicopathological features, including age, gender, smoking status, tumor stage, cancer type, and EGFR mutation status. Results: Total miRNA levels were significantly enriched in EVs compared to the serum. Let-7a-5p was downregulated in EVs from patients with advanced-stage lung cancer (Stage III–IV) compared to those with early-stage cancer and controls (p < 0.05), while no differences were observed in the serum. Conversely, miR-21-3p was significantly upregulated in EVs and serum from advanced-stage patients (p < 0.01) and in adenocarcinoma compared to squamous cell carcinoma (p < 0.05). No significant differences were observed for age, gender, or smoking status. Conclusions: Our findings highlight the differential expression of miRNAs in EVs and the serum, emphasizing the diagnostic potential of EV-associated Let-7a-5p and miR-21-3p in lung cancer. These results suggest that EVs are a more robust source for miRNA biomarkers compared to the serum. Full article

Background: The optimal surgical approach for malignant pleural mesothelioma (PM) remains a topic of debate. While extrapleural pneumonectomy (EPP) offers radical resection, it is associated with significant morbidity. Pleurectomy/decortication (P/D) is less extensive but may offer comparable oncologic outcomes with reduced perioperative risk. This study aimed to conduct a comprehensive systematic review and meta-analysis to systematically evaluate and quantitatively compare survival outcomes, 30-day postoperative mortality, and baseline characteristics between patients undergoing P/D and EPP for PM. Methods: A systematic review was conducted in accordance with the PRISMA guidelines. MEDLINE, Embase, and Scopus were searched up to May 2025. Studies comparing EPP and P/D in PM that reported on survival, mortality, or baseline demographics were included. Data from 24 retrospective studies were extracted. Pooled estimates were calculated using random-effects models. Meta-regression and subgroup analyses were performed by geographic region and publication year. Results: P/D was associated with a significantly improved overall survival compared to EPP in the primary analysis (mean difference = 7.01 months; 95% CI: 1.15–12.86; p = 0.018), with substantial heterogeneity (I² = 98.5%). In a sensitivity analysis excluding one statistical outlier, the survival benefit remained significant (mean difference = 4.31 months; 95% CI: 1.69–6.93), and heterogeneity was markedly reduced. The 30-day mortality rate was also significantly lower for P/D (odds ratio = 0.34; 95% CI: 0.13–0.88; p = 0.027). Patients undergoing P/D were, on average, 3.78 years older than those undergoing EPP (p < 0.001), whereas no significant difference was observed in the sex distribution between groups. Subgroup analyses by region and publication year confirmed the robustness of the findings. Meta-regression did not reveal substantial modifiers of survival. Conclusions: P/D demonstrates superior overall survival and reduced perioperative mortality compared to EPP, without evidence of baseline demographic confounding. These findings, derived from retrospective comparative studies, support the preferential use of P/D in eligible patients, particularly in high-volume centers, given its favorable safety profile and superior median survival. However, the absence of randomized trials directly comparing P/D and EPP and the potential influence of patient selection warrant cautious interpretation, and surgical decisions should be tailored to individual patient factors within a multidisciplinary setting. Full article

Pulmonary carcinoids (PCs) are rare tumors, with an incidence ranging from 0.2 to 2 cases per 100,000 population per year. They account for 1–2% of all invasive pulmonary malignancies and represent approximately one-fourth to one-third of all well-differentiated neuroendocrine tumors (NETs) in the body. PCs are generally classified as low- to intermediate-grade malignant tumors, further subdivided into typical carcinoid (TC) and atypical carcinoid (AC), respectively. These tumors exhibit neuroendocrine morphology and differentiation, originating from mature cells of the pulmonary diffuse neuroendocrine system. Traditionally, they are categorized as central or peripheral based on their location relative to the bronchial tree; however, they can arise anywhere within the lung parenchyma. Over 40% of cases may be detected incidentally on a standard chest X-ray, although contrast-enhanced computed tomography (CT) remains the diagnostic gold standard. Surgical resection is the treatment of choice for PCs, with the goal of complete tumor removal while preserving as much healthy lung tissue as possible. In contrast, advanced cases are typically not amenable to surgery, and medical management is focused on controlling hormone-related symptoms and limiting tumor progression. This review aims to provide an overview of the current diagnostic and therapeutic approaches to pulmonary carcinoids. Full article

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by the accumulation of fibrotic tissue in the lungs, leading to impaired gas exchange and respiratory failure, with a poor prognosis and limited treatment options. Oleuropein, a compound extracted from olive leaves, demonstrates a range of pharmacological activities, including benefits for non-alcoholic fatty liver disease and cardiac fibrosis. This study investigates the therapeutic potential of oleuropein for IPF and its underlying mechanisms. We first established a bleomycin-induced mouse model of pulmonary fibrosis and evaluated the in vivo efficacy of oleuropein. Our findings demonstrated that oleuropein significantly alleviated lung fibrosis and improved pulmonary function. Through in vitro experiments, we found that oleuropein inhibited TGF-β1-induced fibroblast migration, activation, autophagy, and apoptotic resistance, and mechanistically, oleuropein could regulate the TGF-β1/Smad and TGF-β1/mTOR signaling pathways in fibroblasts. Additionally, molecular docking analysis indicated that FAP-α is a potential target of oleuropein, displaying strong binding affinity. The effects of oleuropein on fibroblasts were markedly disrupted in FAP-α knockout cells. In conclusion, oleuropein exerts its beneficial effects by targeting FAP-α and inhibiting TGF-β1-related signaling pathways, improving the pathological characteristics of pulmonary fibrosis in mouse models, and demonstrating promising application prospects for the treatment of IPF. Full article

Background and Clinical Significance: Spinal arachnoid cysts are rare lesions that may become symptomatic through progressive spinal cord compression. We present a complex case of a thoracic extradural SAC in a 17-year-old male, managed through a stepwise, multidisciplinary approach. Case Presentation: The patient presented with progressive lower limb weakness, right knee paresthesia, and urinary hesitancy following physical exertion. MRI revealed a large posterior extradural SAC extending from T2–T3 to T8, with associated spinal cord compression. Initial management involved T8 laminectomy and cyst fenestration under intraoperative neurophysiological monitoring, with partial clinical improvement. However, early recurrence with pseudomeningocele formation prompted a second surgery, including external CSF drainage. Persistent cerebrospinal fluid (CSF) leakage led to targeted epidural blood patching, followed by temporary stabilization. Due to continued cyst enlargement and spinal cord compression, definitive surgical repair was undertaken: fistula clipping at T3 and embolization with platinum coils inside the cystic cavity, combined with a new blood patch. This novel technique resulted in radiological improvement and clinical stabilization. Conclusions: This case highlights the diagnostic and therapeutic challenges of managing symptomatic extradural SACs, particularly in young patients. Our experience underscores the utility of a staged approach involving surgical decompression, neuroimaging-guided interventions, and definitive dural repair. The combination of fistula clipping and coil embolization may offer a promising strategy for refractory cases, potentially reducing recurrence and preserving neurological function. Full article

Background/Objectives: Patients with inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) exhibit complex clinical profiles due to autonomic dysfunction. While sinus node sparing (SNS) hybrid ablation is emerging as a promising therapy, there are no established guidelines worldwide for post-procedure patient management and care is mainly based on telemonitoring. In contrast, our hybrid cardiac rehabilitation (HCR) program integrates inpatient care and home-based telerehabilitation. We aim to evaluate the implementation of the HCR program, patient acceptance and adherence, and the effectiveness of the Malmö POTS scoring system in monitoring disease progression and rehabilitation outcomes. Methods: Patients underwent a personalized HCR program after SNS. The program included early mobilization, psychological support, respiratory therapy, and structured exercise. Clinical outcomes were assessed using symptom burden (Malmö POTS score), ECG parameters, exercise duration, perceived exertion, and rehabilitation adherence. Results: All patients completed the inpatient phase, and 87% completed the home-based phase. In the early postoperative period, pericarditis, anemia, and benign rhythm disturbances were mild and self-limiting. The Malmö POTS score decreased from 65.3 to 25.7. Lower perceived exertion early in the program correlated with clinical improvement. At the 2-month follow-up, 81% of patients no longer met the clinical criteria for IST/POTS without the use of medications. The program was evaluated as safe, feasible, and well-tolerated, with high patient satisfaction. Conclusions: A well-organized hybrid cardiac rehabilitation program after SNS is feasible, safe, and well-tolerated in IST/POTS patients. The Malmö POTS score may support outcome monitoring. The integration of individualized training and telemedicine represents a promising development for patients post-SNS ablation. While this study demonstrates feasibility and potential benefits, further controlled studies are needed to evaluate its impact on long-term recovery and symptom control. Full article

Background/Objectives. Heart rate variability (HRV) is the variability in the beat-by-beat heart period. Primary focal hyperhidrosis (PFHH) is a disease characterized by excessive sweat production, strongly affecting social life. Several authors define this condition as a dysautonomic disorder, mainly driven by exaggerated sympathetic activity. The aim of the study was to demonstrate a possible cardiac involvement in the disease. Other outcomes were the occurrence of dysautonomic disorders after surgery and its possible correlation with baseline characteristics. Methods. This observational, controlled trial enrolled patients with a confirmed clinical diagnosis of severe PFHH candidates to thoracoscopic sympathetic chain clamping. Before and after surgery, ECG was obtained using KardiaMobile 6L (AliveCor^®, Mountain View, CA, USA) device with a five-minute recording and HRV was analyzed using Kubios HRV Premium (Kubios©) software. Results. 111 patients were compared to 222 healthy control subjects. No differences were seen in HRV analysis between the two groups at baseline (time-domain p > 0.05, frequency-domain p > 0.05, autonomic indexes p > 0.05). When comparing autonomic function indexes in patients before and after the surgical procedure, no differences were seen in frequency-domain HRV analysis, but a blunted increase in SNS index (0.2 vs. 1.38, p 0.02). No development of systemic dysautonomic disorders nor significant compensatory hyperhidrosis were seen after the surgery. Conclusions. This study shows that PFHH is a peripheral autonomic nervous system derangement, rather than central. Sympathetic chain clamping resulted safe and effective in improving patients’ conditions, with no risks of dysautonomic disorders. Full article

Objectives: To evaluate outcomes of patients undergoing lung segmentectomy using open thoracotomy, Video-Assisted Thoracoscopic Surgery (VATS), or Robotic-Assisted Thoracoscopic Surgery (RATS) approaches. Methods: A total of 157 patients (mean age: 68.7 years; 58% male) who underwent lung segmentectomy from 2015 to 2024 at the Thoracic Surgery of Siena were retrospectively enrolled and divided into groups based on the surgical approach: thoracotomy (n = 60), VATS (n = 58), and RATS (n = 39). No significant differences were observed between groups in terms of age, gender, or tumor stage. Peri-operative outcomes, and, in patients with non-small cell lung cancer (NSCLC, n = 104), long-term outcomes, were analyzed. Group comparisons were conducted using Kruskal–Wallis, Dunn’s test, Chi-squared, or Fisher’s exact test and Kaplan–Meier analysis with log-rank test. Results: Conversion rate was 13% and 0% for VATS and RATS, respectively (p = 0.005). Pleural effusion on first post-operative day was lower in RATS than VATS (p = 0.0006) and open (p < 0.0001). The maximum Visual Analogue Scale (VAS) value recorded was lower in RATS than open (p = 0.016) and VATS (p = 0.013). Surgery time was longer for RATS than open (p = 0.001) and VATS (p = 0.013). No differences were found in hospital stay and post-operative complications. In patients with NSCLC, the median follow-up was 25 months. The 90-day mortality rate was 9.5% in thoracotomy, 0% in VATS and RATS (p = 0.05). The 1- and 2-year overall survival was higher in VATS and RATS groups than thoracotomy (p = 0.001 and p = 0.040, respectively). The number of harvested lymph nodes was larger in the open group (p = 0.010), while a higher number of stations were harvested in RATS and open than VATS (p = 0.001). No differences were found in local recurrence (p= 0.08). Conclusions: RATS segmentectomy ensures a lower conversion rate, less post-operative pain, reduced daily pleural effusion, and a greater number of harvested lymph node stations compared to VATS, providing comparable peri-operative outcomes. RATS and VATS segmentectomy offer an advantage over the open approach in short- and long-term survival. Full article

Background: This study investigated whether branched thoracic endovascular aortic repair (bTEVAR), a treatment for distal aortic arch diseases, could serve as an alternative to open aortic surgery (OAS). Methods: This single-center, retrospective, observational cohort study comprised 80 patients (bTEVAR, n = 28; TAR, n = 52) treated from October 2012 to June 2018. The median age and median follow-up periods were 73 years (interquartile range [IQR], 66–79 years) and 6.0 years (IQR, 2.8–9.7 years). Results: The patients in the bTEVAR group were older than those in the OAS group (p < 0.001), and the EuroSCORE2 was significantly higher in the bTEVAR group (6.6%) than in the OAS group (2.4%; p < 0.001). There were no 30-day or in-hospital mortalities in either group. Stroke was observed in four (5.0%) patients, all of whom were in the bTEVAR group (p = 0.013). However, no other significant differences were observed between the two groups in other early aortic events. Kaplan–Meier curves regarding the survival, aorta-related death, and aortic events showed no significant differences between the two groups. Conclusions: Although bTEVAR involves an older patient population and a higher surgical risk, the early and mid-term outcomes were comparable to those of OAS, except for cerebral infarction. However, because cerebral infarction significantly reduces a patient’s quality of life, for bTEVAR to become more widespread, it is necessary to reduce the incidence of cerebral infarction. Full article

Early diagnosis of lung cancer, essential for reducing its high mortality rate, is currently challenging, partly due to the lack of specific biomarkers. Here, we attempted to develop a noninvasive and potentially sensitive screening method based on the proteomic analysis of unstimulated and stimulated saliva samples, collected by passive drooling and salivary swabs, respectively, from healthy heavy smokers enrolled in a nonprofit screening project. Protein content analyzed before and after sample cryopreservation for various periods and the associated two-dimensional electrophoresis revealed that protein extraction after short-term cryopreservation prevented the loss of detectable proteins. Mass spectrometric analysis of these electrophoretically resolved proteins revealed the presence of salivary proteins whose levels may be dysregulated in various types of lung cancer. Finally, in pilot experiments conducted on stimulated saliva from a patient with a lung cancer nodule, we detected altered content or selective presence of proteins involved in lung carcinogenesis, such as serpin B3 or the proteins S100A14 and aldoketoreductase-A1, respectively. While acknowledging that these findings require further validation, we believe that the use of saliva and related proteomic analyses may contribute to the identification of potential early lung cancer biomarkers, which could hopefully improve clinical management of the tumor and patient survival. Full article

Background: Thymoma is a malignant tumor originating from the thymic epithelium and can be associated with over 100 paraneoplastic syndromes (PNSs). Due to the low incidence of thymoma and the relative rarity of alopecia areata (AA) as an associated autoimmune disease, patients with thymoma combined with AA are relatively uncommon in clinical practice. As a result, the clinicopathological features and pathogenesis of such patients have been rarely investigated. Methods: This study retrospectively analyzed the clinical records of thymoma patients who underwent surgical treatment at Peking Union Medical College Hospital and Beijing Tongren Hospital from August 2014 to July 2019, with a focus on the clinicopathological features of thymoma patients with AA. Propensity score matching (PSM) was employed to create a 1:5 matched comparison group with thymoma patients without AA. Results: A total of 428 thymoma patients were included, among which 9 had AA. Using PSM, we matched 45 control patients without AA based on age and gender. The analysis revealed that thymoma patients with AA had a significantly higher proportion of myasthenia gravis (MG) [100.00% (9/9) vs. 66.67% (30/45), p = 0.049], although there were no significant differences between the AChR antibodies, Titin antibodies, MG severity, and the incidence of postoperative myasthenic crisis. However, the proportion of thymoma patients with AA who also had other PNSs besides MG was significantly higher [88.89% (8/9) vs. 6.67% (3/45), p < 0.001]. Additionally, CD4⁺/CD8⁺ T-cell inversion in the serum was observed at a much higher rate in thymoma patients with AA [100.00% (9/9) vs. 24.44% (11/45), p < 0.001]. Conclusions: We hypothesize that the pathogenesis of thymoma with AA differs from that of thymoma with MG, though there may be a correlation. The etiology of thymoma with AA may be attributed to abnormal autoimmune CD8⁺ T lymphocytes produced by the thymoma, which can also lead to other cytotoxic T-cell-mediated autoimmune diseases. Full article