Search Results (327)

Multiple sclerosis (MS) is characterized by a continuum of diverse neuroinflammatory and neurodegenerative processes that contribute to disease progression from the earliest stages. This leads to a highly heterogeneous clinical course, requiring early and accurate prognostic assessment: the identification of reliable prognostic biomarkers is crucial to support therapeutic decision-making and guide personalized disease management. In this narrative review, we critically examined the current MS literature, investigating prognostic factors associated with disease progression and irreversible disability in adult-onset MS, with a focus on different clinical, radiological, and molecular biomarkers. Particular attention is directed toward the prognostic value of baseline clinical and neuroimaging factors, emerging biomarkers of smoldering disease, and progression independent of relapse activity (PIRA) events. Additionally, we discussed the role of integrated prognostic tools and risk scores, as well as their potential impact on clinical practice. We aim to provide a comprehensive and clinically oriented synthesis of available evidence in the MS biomarkers field, supporting multifaceted prognostication strategies to improve long-term outcomes in people with MS. Full article

Background/Objectives: This single-cohort follow-up study describes the median overall survival (OS) in patients with unresectable head and neck squamous cell carcinoma (HNSCC) due to invasion of vital structures, which is under-represented in the current literature. Secondarily, subgroups were evaluated according to the type of presentation, in order to identify clinical characteristics and contribute to developing an appropriate treatment plan and managing patient’s expectations. Methods: This single-cohort observational study analysed the OS of 39 patients from the Otolaryngology Department with advanced-stage head and neck cancer with invasion of vital anatomical structures considered ineligible for surgical treatment. Secondarily, subgroups were evaluated according to type of presentation and various clinical characteristics. Results: A total of 39 patients radiologically classified as having unresectable HNSCC (i.e., unsuitable for surgical resection), with a mean age of 66.87 years, were included during a 24-month follow-up. By the end of the study, 56.4% of the patients had died. The median OS was 16.09 months. Statistically significant differences were observed when comparing human papilloma virus (HPV)-positive and -negative status and when comparing initial and recurrent tumours. Conclusions: The invasion of anatomical structures such as the skull base, internal carotid artery, and prevertebral space was associated with a marked decrease in survival, with an OS time of 16 months. This study provides valuable evidence in patients with unresectable HNSCC, highlighting tumour recurrence and HPV-negative status as important indicators of poor prognosis. Full article

Background: Multisegmental lumbar degenerative disease (ms-LDD) is a common condition in older adults, often requiring surgical intervention. While rigid stabilization remains the gold standard, it is associated with complications such as adjacent segment disease (ASD), higher blood loss, and longer recovery times. The Dynesys dynamic stabilization system offers an alternative by preserving motion while stabilizing the spine. However, data comparing Dynesys with fusion in multisegmental cases are limited. Objective: This study evaluates the clinical and radiographic outcomes of Dynesys dynamic stabilization versus rigid stabilization in the treatment of ms-LDD. Methods: A retrospective analysis was conducted on 53 patients (mean age: 62.25 ± 15.37 years) who underwent either Dynesys dynamic stabilization (n = 27) or PLIF (n = 26) for ms-LDD involving at least seven motion segments. Clinical outcomes were assessed using the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI), while radiological parameters such as lumbar lordosis (LL), sagittal vertical axis (SVA), and spinopelvic parameters (pelvic incidence, pelvic tilt and, sacral slope) were analyzed. A two-stage surgical approach was employed in the Dynesys group to enhance osseointegration, particularly in elderly osteoporotic patients. Results: Both groups showed significant improvements in VAS and ODI scores postoperatively (p < 0.001), with no significant differences between them. However, the Dynesys group demonstrated superior sagittal alignment correction, with a significant increase in LL (p < 0.002) and a significant decrease in SVA (p < 0.0015), whereas changes in the rigid stabilization group were not statistically significant. Additionally, the Dynesys group had fewer complications, including a lower incidence of ASD (0 vs. 6 cases). The two-stage technique facilitated improved screw osseointegration and reduced surgical risks in osteoporotic patients. Conclusions: Dynesys dynamic stabilization is an effective alternative to rigid stabilization in ms-LDD, offering comparable pain relief and functional improvement while preserving motion and reducing ASD risk. The two-stage approach enhances long-term stability, making it particularly suitable for elderly or osteoporotic patients. Further long-term studies are needed to confirm these findings. Full article

Background: Atypical carcinoid of the thymus is an exceptionally rare neuroendocrine tumor originating from neuroendocrine cells within the thymus. These tumors often present with no symptoms or with nonspecific clinical signs, making early diagnosis particularly challenging. Despite their rarity, atypical carcinoids are clinically significant due to their aggressive nature and relatively poor prognosis. Early detection and appropriate management are therefore crucial to improving patient outcomes. Results: In this report, we present the case of a 64-year-old patient in whom an atypical carcinoid of the thymus was incidentally discovered following a thoracic computed tomography scan performed for unrelated reasons. Imaging revealed a suspicious anterior mediastinal mass, which was subsequently surgically resected. Histopathological examination, supported by immunohistochemical analysis, confirmed the diagnosis of an atypical carcinoid of the thymus. The tumor demonstrated coexpression of epithelial and neuroendocrine markers, consistent with this rare entity. Conclusions: This case adds to the limited body of literature on atypical carcinoid of the thymus and highlights the importance of considering this diagnosis when evaluating anterior mediastinal masses. It also underscores the value of thorough radiological and pathological assessment in identifying early-stage disease, which may significantly influence prognosis and therapeutic strategies. Full article

Background: Secukinumab is a fully human monoclonal antibody that targets interleukin (IL)-17A and is used to treat axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Treating axSpA and PsA can be challenging in patients with comorbidities. In this multicenter retrospective study, we aimed to evaluate the efficacy and safety of secukinumab treatment in patients with axSpA and PsA who had a history of tuberculosis, multiple sclerosis (MS), or congestive heart failure (CHF). Methods: The study included 44 patients with a diagnosis of axSpA and PsA and a history of tuberculosis, MS, or CHF who received secukinumab treatment at 13 centers in our country. Erythrocyte sedimentation rate, C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Disease Activity Score CRP, visual analog scale, and Disease Activity Score-28 CRP markers at months 0, 3, and 12 of secukinumab treatment were analyzed. Alongside this, tuberculosis, MS, and CHF were evaluated at follow-up using clinical assessments and imaging methods such as chest radiographs, brain magnetic resonance, and echocardiography. Results: A statistically significant improvement in inflammatory markers and disease activity scores was observed in patients treated with secukinumab. There was no reactivation in patients with a history of tuberculosis. In most MS patients, the disease was stable, while clinical and radiological improvement was observed in one patient. No worsening of CHF stage was observed in patients with a history of CHF. Conclusions: With regular clinical monitoring, secukinumab may be an effective and safe treatment option for axSpA and PsA patients with a history of tuberculosis, MS, or CHF. Full article

Background/objectives: Despite advancements in early diagnosis and clinical practices guided by standardized care protocols, Merkel cell carcinoma (MCC) is marked by an unfavorable prognosis with a 5-year relative survival rate of 65%, based primarily on data collected prior to the introduction of immunotherapy. Regional nodal metastases affect 40–50% of MCC patients, while approximately 33% experience distant dissemination. Among these, bone and bone marrow metastases are particularly notable, although the characteristics and clinical implications of this metastatic disease in MCC remain poorly understood. Methods: A comprehensive review was conducted using the Medline database (via PubMed) up to January 2025. The search strategy included the string “(Merkel cell carcinoma AND (bone OR marrow))”. Results: A total of 1133 (69.3% male and 30.7% female) patients diagnosed with advanced MCC were collected. The median (IQR) age at diagnosis was 67.5 (12.65) years old. Overall, 201 (20.8%) cases of bone and/or bone marrow metastases were identified and linked to a primary known MCC in 75.7% of cases. Bone metastases (BMs) appear as the third most common metastatic site, following the liver (second) and lymph nodes (first). They show mixed biological and radiological behavior, with a marked preference for the axial skeleton over the appendicular one. Addressing the characteristics of metastatic bone disease, neurological symptoms were the most documented, whereas bone marrow involvement and leukemic spread seemed to be primarily related to immunosuppression. Multimodal treatment strategies, including platinum-based chemotherapy and radiotherapy, were the primary approaches adopted, reflecting therapeutic practices from the pre-immunotherapy era. Conclusions: The pattern of metastatic spread in MCC differs among studies, with the bones resulting as the third most common site of distant spread. Excluding head and neck MCC, which seems to be more regularly associated with liver metastases, the relationship between the primary tumor site and the development of bone or bone marrow metastases appears inconsistent. Overall, BMs mostly correlated with advanced MCC stages and poorer survival outcomes, with a median overall survival (OS) of 8 months (range 12.75–4). The integration of international guidelines, evolving evidence from clinical trials, and the expanding role of immune checkpoint inhibitors (ICIs) will contribute to improving systemic disease control and enhance patient care. Full article

Background/Objectives: The most common limb-salvage procedure for end-stage ankle arthropathy with severe bone defect is arthrodesis. Successful fusion requires rigid metal fixation, effective filling of the bone defect space, and maximal securing of the contact area between the tibia and talus. In cases with severe bone defect, sufficient grafting using autogenous bone alone is limited, and there is still controversy regarding the effectiveness of allogeneic or xenogeneic bone grafting. This study aimed to evaluate the intermediate-term clinical outcomes after shortening arthrodesis using fibular osteotomy for ankle arthropathy with severe bone defect. Methods: Twenty-two patients with shortening ankle arthrodesis were followed up ≥ 3 years. All operations were performed by one senior surgeon and consisted of internal fixation with anterior fusion plate, fibular osteotomy, and autogenous bone grafting. The causes of ankle joint destruction were failed total ankle arthroplasty (7 cases), neglected ankle fracture (6 cases), delayed diagnosis of degenerative arthritis (5 cases), avascular necrosis of talus (2 cases), and diabetic neuroarthropathy (2 cases). Clinical outcomes including daily living and sport activities were evaluated with the Foot and Ankle Outcome Score (FAOS) and the Foot and Ankle Ability Measure (FAAM). Radiological evaluation included fusion rate, time to fusion, leg length discrepancy, and degenerative change in adjacent joints. Results: The FAOS and FAAM scores significantly improved from a mean of 21.8 and 23.5 points preoperatively to 82.2 and 83.4 points at final follow-up, respectively (p < 0.001). Visual analogue scale for pain during walking significantly improved from a mean of 7.7 points preoperatively to 1.4 points at final follow-up (p < 0.001). The average time to complete fusion was 16.2 weeks, and was achieved in all patients. The average difference in leg length compared to the contralateral side was 11.5 mm based on physical examination, and 13.8 mm based on radiological examination. During the average follow-up of 56.2 months, no additional surgery was required due to progression of degenerative arthritis in the adjacent joints, and no cases required the use of height-increasing insoles in daily life. Conclusions: Shortening ankle arthrodesis using fibular osteotomy and anterior fusion plate demonstrated satisfactory intermediate-term clinical outcomes and excellent fusion rate. Advantages of this procedure included rigid fixation, preservation of the subtalar joint, effective filling of the bone defect space, and maximal securing of the contact area for fusion. The leg length discrepancy, which was concerned to be a main shortage, resulted in no significant clinical symptoms or discomfort in most patients. Full article

Background and Objectives: The clinical value of HER2-low breast cancer (BC), defined by immunohistochemistry (IHC) scores of 1+ or 2+/ISH-negative without HER2 amplification, remains unclear in the neoadjuvant setting. This study aimed to determine whether HER2-low and HER2-zero tumors differ in pathological complete response (pCR) rates and disease-free survival (DFS) among early-stage breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Materials and Methods: We retrospectively analyzed 134 early BC patients treated with NAC between 2017 and 2023. Patients were categorized as HER2-zero (IHC 0) or HER2-low (IHC 1+ or 2+/ISH–). The primary endpoint was total pCR (tpCR); secondary endpoints included breast (bpCR), nodal (npCR), and radiologic complete response (rCR), alongside DFS analysis stratified by hormone receptor (HR) status. Results: Of the cohort, 91 patients (67.9%) were HER2-zero and 43 (32.1%) were HER2-low. There was no statistically significant difference in tpCR (26.4% vs. 27.9%, p = 0.852), bpCR (28.6% vs. 30.2%, p = 0.843), npCR (37.4% vs. 32.6%, p = 0.588), and rCR (23.1% vs. 30.2%, p = 0.374) between HER2-zero and HER2-low groups. DFS did not significantly differ between HER2-zero and HER2-low groups overall (p = 0.714), nor within HR-positive (p = 0.540) or TNBC (p = 0.523) subgroups. Conclusions: HER2-low tumors demonstrated similar pathological responses and survival outcomes compared to HER2-zero tumors. While a HER2-low status does not appear to define a distinct biological subtype in early BC, it remains a relevant classification for emerging HER2-targeted therapies, needing further investigation in prospective studies. Full article

Background: Eighty-five percent of peri-implant malignancies are oral squamous cell carcinomas (OSCCs), and most of them are misdiagnosed as peri-implantitis because of their clinical and radiological presentation; few studies have focused on addressing and solving the diagnostic issues related to peri-implant OSCCs. Objectives: The study aimed to describe the clinicopathological features of peri-implant OSCCs and to report the staging issues related to the diagnosis of these lesions. Methods: This retrospective cohort study included patients who received a diagnosis of and treatment for peri-implant OSCCs at the Unit of Dentistry of the “Aldo Moro” University of Bari (Italy) from 2018 to 2024. By using descriptive statistics, the authors highlighted the diagnostic issues related to the clinical presentation, radiological features, and histology of peri-implant OSCCs. Results: A total of 13 women and 8 men with a mean age of 70.6 ± 11.7 years met the inclusion criteria; the medical history of the participants showed potentially malignant disorders (OPMDs) in 52.4% of patients, whereas 14.3% had already developed an OSCC. The patients showed 24 peri-implant OSCCs; the clinical presentation was leuko-erythroplakia-like (41.7%) or erythroplakia-like (58.3%), thus simulating peri-implantitis; in addition, 52.0% of dental implants involved had a probing pocket depth ≥ 10 mm, further mimicking peri-implantitis. Panoramic radiograms and cone beam computed tomography were of little use in studying bundle bone–implant interfaces; in particular, the tomography showed circumferential bone resorption only in peri-implantitis-like OSCCs. In total, 91.6% of histological examinations of OSCCs showed peri-implantitis-like inflammation; early-stage lesions (pTNM I-II) accounted for 33.3%, whereas late-stage lesions (pTNM III-IV) accounted for 66.7%; lymph nodal metastases occurred in 25.0% and 62.5%, respectively. The mean follow-up was 3.4 ± 1.0 years; all patients with OPMDs had poorly differentiated tumors and thus showed a worse prognosis than those without OPMDs (mean disease-free survival of 15.5 ± 7.7 months and 44.7 ± 12.1 months, respectively). Conclusions: The results of the study showed that peri-implant OSCCs occurred most frequently in patients with OPMDs or previous OSCC; in addition, peri-implant OSCCs required demolition rather than conservative excision, and the prognosis of patients strictly depended on the grade of the cancer. In the authors’ experience, the clinical–radiological presentation simulating peri-implantitis was the feature that concurred most in complicating the diagnosis of those tumors. Full article

Background and Objectives: The accurate segmentation of pulmonary nodules in computed tomography (CT) remains a critical yet challenging task due to variations in nodule size, shape, and boundary ambiguity. This study proposes CAAF-ResUNet (Context-Aware Adaptive Attention Fusion ResUNet), a novel deep learning model designed to address these challenges through adaptive feature fusion and edge-sensitive learning. Materials and Methods: Central to our approach is the Adaptive Attention Controller (AAC), which dynamically adjusts the contribution of channel and position attention based on contextual features in each input. To further enhance boundary localization, we incorporate three complementary boundary-aware loss functions: Sobel, Laplacian, and Hausdorff. Results: An extensive evaluation of two benchmark datasets demonstrates the superiority of the proposed model, achieving Dice scores of 90.88% on LUNA16 and 85.92% on LIDC-IDRI, both exceeding prior state-of-the-art methods. A clinical validation of a dataset comprising 804 CT slices from 35 patients at the University Medical Center of Ho Chi Minh City confirmed the model’s practical reliability, yielding a Dice score of 95.34% and a notably low Miss Rate of 4.60% under the Hausdorff loss configuration. Conclusions: These results establish CAAF-ResUNet as a robust and clinically viable solution for pulmonary nodule segmentation, offering enhanced boundary precision and minimized false negatives, two critical properties in early-stage lung cancer diagnosis and radiological decision support. Full article

Background: The role of neoadjuvant endocrine therapy (NET) in patients with luminal tumors is still not well defined in everyday clinical practice. To assess the efficacy of combination NET, we analyzed the outcomes of fulvestrant and aromatase inhibitors (AI) in combination in a real-world population. Methods: This was a single-arm, retrospective longitudinal study of the total population of patients diagnosed with locoregionally advanced, clinical stage II-III, HR+ HER2-, luminal-type eBC, who were treated with the neoadjuvant combination of fulvestrant and AI between 2019 and 2024 at the Clinical University Hospital of Split, Croatia. Results: We enrolled 44 patients in the intention-to-treat (ITT) population, while 34 completed NET and surgery (per-protocol population; PPP). The median duration of NET was 11 months (interquartile range [IQR] of 9–16 months). The best radiological objective response rate (partial or complete response) was achieved by 30 (68.2%) in ITT, and 26 (76.5%) in PPP, defined by radiological examination, breast ultrasound, or MR. In the PPP, the minimal or moderate pathological response according to residual cancer burden (I or II) was observed in 29 (85.3%) patients. The median of absolute changes in Ki-67 was −5 (95% CI: −9 to 0), and the median of relative Ki67 changes was −40% (95% CI: −72% to 0%). Post-surgical Ki-67 was significantly predicted by initial Ki-67, positive lymph nodes, and time from diagnosis to the initiation of NET. Treatment was well tolerated, with no therapy discontinuation or dose reductions needed due to toxicity. The most commonly reported side effects included musculoskeletal pain (45.5%), asthenia (34.1%), and hot flashes (29.5%). Conclusions: Dual hormonal therapy with fulvestrant and AI is an active, easily given, non-toxic, promising neoadjuvant treatment in real-world patients with locally advanced luminal-type eBC who are not candidates for chemotherapy. Full article

Background: Invasive aspergillosis with orbital apex and intracranial involvement is rare and often misdiagnosed due to nonspecific imaging findings. Misinterpretation may lead to inappropriate therapies, such as corticosteroids, which can exacerbate fungal infections. Case Presentation: A 50-year-old immunocompetent woman with diabetes mellitus presented with right ptosis and systemic malaise. Magnetic resonance imaging (MRI) performed three months prior had shown a subtle low-signal lesion in the right orbital apex. The lesion was small and thought to represent a granulomatous process, with minimal systemic inflammation and only mild surrounding changes on imaging. Biopsy was considered too invasive at that stage, and the patient was placed under observation. Over time, her condition progressed, and repeat imaging revealed intracranial extension, including involvement of the cavernous sinus and frontal lobe. Differential diagnoses included granulomatous diseases such as sarcoidosis or tuberculosis, prompting empirical anti-tuberculosis treatment. However, the patient’s condition worsened, and biopsy of the sphenoid sinus revealed septated fungal hyphae consistent with Aspergillus species on Grocott staining. Voriconazole therapy was initiated, resulting in significant clinical and radiological improvement. Discussion: This case highlights the diagnostic challenge of identifying orbital apex aspergillosis with early MRI changes and demonstrates the risk of misdiagnosis as granulomatous disease. Differentiating fungal infections from other inflammatory etiologies based on subtle imaging features is critical, especially when considering immunosuppressive therapy. Conclusion: Clinicians should maintain a high index of suspicion for fungal infections in patients with progressive orbital apex lesions, even in the absence of classic immunosuppression. Early imaging review and biopsy are essential to prevent misdiagnosis and inappropriate treatment. Full article

Lung cancer remains the leading cause of cancer-related mortality globally, largely due to late-stage diagnoses. While low-dose computed tomography (LDCT) has improved early detection and reduced mortality in high-risk populations, traditional screening strategies often adopt a one-size-fits-all approach based primarily on age and smoking history. This can lead to limitations, such as overdiagnosis, false positives, and the underrepresentation of non-smokers, which are especially prevalent in Asian populations. Precision medicine offers a transformative solution by tailoring screening protocols to individual risk profiles through the integration of clinical, genetic, environmental, and radiological data. Emerging tools, such as risk prediction models, radiomics, artificial intelligence (AI), and liquid biopsies, enhance the accuracy of screening, allowing for the identification of high-risk individuals who may not meet conventional criteria. Polygenic risk scores (PRSs) and molecular biomarkers further refine stratification, enabling more personalized and effective screening intervals. Incorporating these innovations into clinical workflows, alongside shared decision-making (SDM) and robust data infrastructure, represents a paradigm shift in lung cancer prevention. However, implementation must also address challenges related to health equity, algorithmic bias, and system integration. As precision medicine continues to evolve, it holds the promise of optimizing early detection, minimizing harm, and extending the benefits of lung cancer screening to broader and more diverse populations. This review explores the current landscape and future directions of precision medicine in lung cancer screening, emphasizing the need for interdisciplinary collaboration and population-specific strategies to realize its full potential in reducing the global burden of lung cancer. Full article

Periodontitis is a severe infection that damages the bone surrounding teeth, making severity assessment challenging for dentists. Utilizing artificial intelligence (AI) techniques enhances diagnostic accuracy in radiographic analysis, enabling a more efficient and precise diagnosis. The aim of this research is to develop an AI-based diagnostic system comprising two deep learning stages, designed to efficiently detect and classify periodontitis from panoramic radiographs. In the proposed two-stage system, a binary classifier is first utilized to determine the presence of periodontal bone loss, which is then localized and classified by the second AI model. Based on our extensive research, we concluded that convolutional neural networks (CNNs) are the most effective type of neural network for addressing our problem. To ensure the accuracy and reliability of results, we developed two robust CNN models, YOLOv8 and MobileNet-v2, that have shown significant performance in similar applications. The primary model, MobileNet-v2, was utilized to detect periodontitis in panoramic radiographs, while the secondary model, YOLOv8, was developed to localize the affected regions and classify the severity level of the periodontitis. A custom dataset was created to comprise 817 panoramic images. Our developed YOLOv8 model achieved a testing precision of 0.74 and a recall of 0.7, while the MobileNet-v2 model achieved a testing accuracy of 0.88 and a recall of 1.0. These results were further validated by an oral radiology specialist to ensure their accuracy and reliability. Our proposed system is considered to be efficient, cost-effective, and easy to use compared to existing systems in the literature and similar software services available in the market for enhancing diagnosis of periodontitis in clinical practice. Full article

Background/Objectives: This retrospective study evaluates the predictive role of magnetic resonance imaging (MRI) in complications and recurrence in rectal cancer patients undergoing surgery and neoadjuvant therapy, highlighting the impact of structured reporting templates on MRI quality. Compared to traditional free-text reports, structured radiology reports offer a point-by-point evaluation, improving clarity and completeness by thoroughly addressing all relevant findings. MRI is critical in rectal cancer staging, guiding treatment based on tumor characteristics like T stage, sphincter involvement, vascular invasion, and lymph node status. Methods: A retrospective analysis of MRI and reports from 67 rectal cancer patients at the time of diagnosis, who were subsequently treated with neoadjuvant radiochemotherapy and surgery, was conducted. MRI report features, including tumor location, morphology, T stage, sphincter infiltration, mesorectal fascia involvement, lymph nodes, and extramural vascular invasion, were evaluated against European Society of Gastrointestinal and Abdominal Radiology (ESGAR) recommendations. Multivariate and univariate analyses were performed to correlate MRI findings with postoperative outcomes such as complications, local recurrence, bleeding, and 30-day anastomotic leaks. Results: Sphincter involvement showed a strong association with increased complications (multivariate β = 0.410, univariate r = 0.270). Extramural vascular invasion was linked to higher rates of local recurrence (multivariate β = 0.199, univariate r = 0.127). Lymph node involvement correlated with an elevated risk of postoperative bleeding (multivariate β = 0.133, univariate r = 0.293). Additionally, advanced T staging predicted a higher incidence of 30-day anastomotic leaks (multivariate β = 0.210, univariate r = 0.261). These findings may provide clinically relevant insights to support personalized surgical planning and improve preoperative risk stratification. Conclusions: Detailed MRI reporting, aligned with structured templates, significantly guides surgical and therapeutic strategies in rectal cancer management. However, the retrospective nature of the study and the limited sample size may affect the generalizability of the results. Full article