Search Results (346)

Choosing the optimal first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangements can be challenging in daily practice. Although clinical trials with next-generation ALK-tyrosine kinase inhibitors (TKIs) have played a key role in evaluating their efficacy and safety, which patients benefit from a specific ALK-TKI may still be questioned. The methodological inconsistencies in these trials, which led to the inclusion of different patient populations, appear to have been inadequately addressed. ALK-rearranged NSCLC is a heterogeneous disease, and co-existing molecular alterations may affect the outcome. The questions explored in these trials appear insufficient to support a personalized approach to the first-line treatment, while defining long-term responders and early progressors would be clinically useful. This narrative review presents several considerations from oncologists’ and pathologists’ perspectives. We propose defining favorable and unfavorable features, such as histology, type of ALK fusion, co-existing molecular alterations, plasma circulating tumor DNA (ctDNA, performance status, and brain metastases, to help identify patients with lower and higher risk of progression. Consequently, the most potent ALK-TKI to date, Lorlatinib, may be considered as the first-line treatment for high-risk patients with unfavorable features, while sequencing of ALK-TKIs may be appropriate for low-risk patients with favorable features. Although ALK signal inhibition is critical in this disease, it may not be sufficient for clinical control due to de novo co-alterations. A more personalized approach to first-line therapy requires consideration of risk factors for each patient. Full article

Background: Our study investigated the association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer (TC). Methods: A retrospective review of 1670 patients who underwent thyroid surgery between October 2022 to February 2025 was performed. The clinicopathological characteristics of patients with TC and CLT were collected. CLT was diagnosed histopathologically. Results: Patients with a positive CLT result (60.39%) compared to a negative CLT result (34.12%) had more frequently TC (p < 0.001), predominantly PTC. In univariate analysis, patients with malignancy + CLT-positive compared to malignancy + CLT-negative were found to be younger in age (p < 0.001), female gender (p < 0.001), smaller tumours focus (p = 0. 013), smaller mass of thyroid removed (p < 0.001) and more often Bethesda category V and VI (p = 0.019), true positive fine needle aspiration biopsy (FNAB) for PTC (p = 0.009), and microcarcinoma (p = 0.021). There were no differences in multifocality, the presence of LNM, or the number of LNMs. The location of metastases at neck lymph nodes was at the borderline of significance (p = 0.065). In multivariate analysis, after accounting for Bethesda and age, CLT+ was found to increase the risk of TC by 73% (OR = 1.73; 95%CI, 1.15-2.29), while the risk of PTC increased more than 2-fold (OR = 2.12; 95% CI, 1.45–3.11). CLT had no statistically significant effect on the presence of LNM. Conclusions: We found that CLT is a risk factor for TC. One should be vigilant concerning the coexistence of these two diseases. We suggest that total thyroidectomy should be considered in patients referred for thyroid nodules and suspected CLT. However, this issue requires further research. Full article

Background/Objectives: Patients with inflammatory bowel disease (IBD) are at an increased risk of various cancers; such as colorectal cancer; skin cancer; bile duct cancer; or lymphoma; with IBD itself not being the sole cause. Inappropriate or ineffective IBD therapy with a continuous inflammatory burden within the gut leads to an increased risk of malignancy. Our study aimed to investigate the risk of malignancy in our patient cohort; focusing on concomitant therapy; disease duration; and inflammatory burden. Methods: A total of 333 consecutive adult patients with IBD (Crohn’s disease; ulcerative colitis; and IBD unclassified) were included in this study. Data from patients were collected retrospectively using patient charts. The patients were treated in the gastroenterological outpatient clinic of the University Hospital of Augsburg; Germany; between 1 January 2014 and 31 December 2018. Results: The study group included 333 patients; 32 (9.61%) of whom suffered from malignancy (any form). Men (n = 21; 65.62%) tended to develop malignancy more often than women (n = 11; 34.38%, p = 0.051). It was also observed that the probability of developing cancer was 2.40 times higher in male patients than in female patients in our cohort. However, this trend was non-significant (HR = 2.412; p = 0.075). Furthermore; the probability of developing cancer increased with the increasing age at the time of the first diagnosis of IBD (HR = 1.088; p < 0.025). A total of 20 patients (6.00%) received their cancer diagnosis after being diagnosed with IBD. The majority of those patients had skin (n = 6; 30.00%) or colon cancer (n = 5; 25.00%). Other diseases such as CML; NHL; HL; HCC; liver sarcoma; prostate cancer; breast cancer; seminoma; thyroid cancer (a second cancer in one of the patients); or CUP syndrome/lung cancer were diagnosed in single patients. Patients with IBD and colon cancer (n = 5; 25.00%) shared some of the known risk factors for tumour development; such as a long-lasting IBD (n = 5; 100.00%), diagnosis at a young age (under 30; n = 3; 60.00%), and the coexistence of PSC (n = 1; 20.00%). The cancer prevalence rate was relatively low in our cohort despite the use of diverse biologics and immunosuppressive drugs. Faecal calprotectin was confirmed as a relevant tool for inflammation monitoring in this cohort. Conclusions: In our study cohort; we could show a low prevalence rate of malignancy in IBD. There were more malignancies in men and in patients who were diagnosed with IBD at later ages. It can be observed that the prevalence rate of cancer was relatively low despite the use of diverse biologics and immunosuppressive drugs; which is the major conclusion of this study. Additionally; the known correlation between elevated levels of faecal calprotectin and gut inflammation was confirmed through our statistical analysis. The use of calprotectin as a non-invasive screening tool for gut inflammation is advised. Full article

Objectives: Upper urinary tract urothelial cell carcinoma (UTUC) in kidney transplant recipients (KTRs) presents distinct clinical challenges due to the complexities of managing both cancer and the long-term immunosuppressive therapy required to preserve graft function. UTUC in this population often presents at advanced stages, contributing to poorer outcomes compared to immunocompetent individuals. Methods: This systematic review (SR) evaluates the incidence, clinical presentation, treatment approaches, and survival outcomes of UTUC in KTRs, based on 16 retrospective studies including 526 patients. Results: The present study highlights a predominance of female patients (ranging from 50% to 91.6%) and significant variability in time to diagnosis (from 7 to 181 months post-transplant). Tumor characteristics also showed considerable heterogeneity, with high-grade and advanced-stage (T3–T4) tumors being more common. The standard treatment for UTUC in KTRs remains radical nephroureterectomy (RNU), with additional resection of the bladder (TURB) when bladder cancer (BC) coexists. Survival outcomes vary significantly, with 5-year overall survival (OS) rates ranging from 16.7% to 90.9%, strongly influenced by tumor stage at diagnosis. This SR further reports high rates of bladder recurrence (18.8% to 61.2%) and challenges in balancing effective cancer treatment with graft preservation. The variability in immunosuppressive regimens across studies complicates the assessment of their role in UTUC progression. The limitations of the current evidence include small sample sizes, retrospective designs, and inconsistent follow-up durations. Conclusions: This SR underscores the need for tailored treatment strategies and improved long-term surveillance. Future research should focus on prospective studies with larger cohorts, exploring the impact of immunosuppression and novel therapies on UTUC outcomes in KTRs. Full article

Background: Idiopathic pulmonary fibrosis (IPF) and emphysema often coexist in patients with lung cancer (LC), forming a syndrome with combined pulmonary fibrosis and emphysema (CPFE). The three share the pathogenic mechanisms of smoking, chronic inflammation, and oxidative stress. The clinical management of CPFE patients is challenging, but its impact on tumor characteristics, acute exacerbation (AE), and prognosis is still controversial. The purpose of this study was to clarify the effect of CPFE on tumor biological behavior, AE risk, and survival outcome in patients with IPF-LC so as to optimize individualized treatment strategies. Methods: This was a retrospective and single-center study. Newly diagnosed LC patients with IPF, COPD, and normal lungs were recruited in the west China hospital. Patients with IPF were further categorized into CPFE-LC and isolated IPF-LC groups based on the presence of emphysema. Clinical and tumor features, lung function parameters, and prognosis were obtained and compared. Results: Patients with IPF and LC were more common in older men and heavy smokers. IPF-associated tumors had a higher proportion of carrying EGFR wild-type, occurring in the lower lobe of the lung and developing adenocarcinoma and squamous cell carcinoma. Among IPF-LC patients, 68.2% (103/151) met CPFE criteria. Pulmonary function tests demonstrated preserved VC% but significantly reduced FEV1/FVC in CPFE versus non-emphysema IPF (76.3% vs. 80.7%, p = 0.004), alongside elevated CPI and impaired DLCO. CPI ≥ 40 (HR = 2.087, 95%CI: 1.715–6.089, p = 0.012), combined with COPD (HR = 2.281, 95%CI: 1.139–4.569, p = 0.040), isolated IPF (HR = 5.703, 95%CI: 2.516–12.925, p < 0.001), and CPFE (HR = 6.275, 95%CI: 3.379–11.652, p < 0.001), were independent prognostic risk factors in LC patients. The incidence of treatment-induced AEs (49.5% vs. 29.2%, p = 0.038) and AE-related mortality (28.0% vs. 11.8%, p = 0.045) were significantly higher in the CPFE group than in the isolated IPF group. Logistic regression analysis showed that CPFE (OR: 3.494, 95%CI: 2.014–6.063, p = 0.001) was independently associated with the risk of AE-related mortality in patients with LC and IPF. Conclusions: Compared to LC patients with solely IPF, the presence of emphysema had no significant impact on overall survival, but CPFE increased the risk of treatment-triggered AE and was associated with AE-related mortality. In patients with LC, CPFE with AEs had a worse prognosis than IPF with AEs. Full article

Helicobacter pylori and Candida spp. are widespread microorganisms found in the human gastrointestinal tract, often coexisting in the same ecological niche. H. pylori, a Gram-negative bacterium, is a well-known pathogen responsible for gastritis, peptic ulcers, and gastric cancer. In contrast, Candida fungi, often detected in food, particularly Candida albicans, are generally considered commensal organisms, but can become opportunistic pathogens under certain conditions. Recent studies suggest a possible link between these microorganisms, highlighting a new survival strategy of H. pylori, that is, its ability to internalize in Candida vacuoles. This phenomenon, confirmed by various microscopic and molecular techniques, may provide H. pylori with protection against adverse environmental conditions, especially clinically important antibiotic therapy. The basic premise of this theory is the ability of H. pylori to penetrate vacuoles in fungal cells, which then become a reservoir of infection, allowing the infection to recur. Understanding the interaction between H. pylori and Candida may offer new insights into the pathogenesis of gastrointestinal diseases and may lead to the development of treatments targeting both organisms simultaneously. The purpose of this article is to review the literature, considering the first observations on this problem in the literature and the current state of knowledge, and to suggest a direction for further research. Full article

Background and Objectives: Along with the ageing of the population, cancer and cardiovascular (CV) diseases more frequently coexist, complicating patients’ management. Here, we focus on elderly oncologic patients, describing clinical features and comorbidities, discussing therapeutic management CV risk factors and CV complications risen during our CV follow-up, and exploring the different items of the comprehensive geriatric assessment (CGA) and the correlation between cardiac function by means of standard 2D echocardiography and each of the CGA items. Methods: A total of 108 consecutive patients (mean age 73.55 ± 5.43 years old; 40.7% females) referred to our cardio-oncology unit were enrolled, and three different groups were identified: Group 1, patients naïve for oncologic treatments (mean age 73.32 ± 5.40; 33% females); Group 2, patients already on antineoplastic protocols (mean age 73.46 ± 5.09; 44.1% females); and Group 3, patients who had already completed cancer treatments (mean age 74.34 ± 6.23; 55% female). The correlation between CGA, performed in a subgroup of 62 patients (57.4%), and echocardiographic parameters was assessed. Results: Group 2 patients had the highest incidence of CV events (CVEs) (61.8% vs. 14.8% in Group 1, 15% in Group 3; p ≤ 0.001) and withdrawals from oncologic treatments (8.8% vs. none in Group 1; p = 0.035). Group 2 had worse 48-month survival (47.1% vs. 22.2% in Group 1, 20% in Group 3; p = 0.05), which was even more evident when focusing on patients who died during follow-up. When assessing echocardiographic parameters, physical activity showed an inverse correlation with the left ventricular mass index (p = 0.034), while the Frailty index showed a direct correlation with the E/e’ ratio (p = 0.005). Conclusions: A thorough baseline CV assessment is important in elderly oncologic patients eligible for anticancer treatment. In this population, CGA can be a simple, feasible screening tool that might help identify patients at a greater risk of developing CVEs correlating to several pivotal cardiovascular parameters. Full article

Cancer constitutes a significant global health challenge, ranking among the leading contributors to worldwide mortality. The inherent limitations of conventional oncologic interventions, particularly their frequent inability to induce durable remissions in advanced malignancies, continue to drive transformative explorations into novel therapeutic paradigms. In recent years, bacteria-based therapies have gained recognition in the management of solid tumors. Compared to traditional therapeutic modalities, extensive research has demonstrated that bacteria possess remarkable anticancer properties. Gut bacteria, which naturally coexist within the human body, represent a unique category of living cells with inherent advantages for solid tumor treatment. These microorganisms are characterized by their relative safety, ease of cultivation, and potential for use in precision medicine through genetic modifications. Furthermore, gut bacteria exhibit diverse mechanisms of action against tumor cells, with different bacterial species potentially exerting synergistic effects. However, the precise anticancer mechanisms of these bacteria, particularly those of gut microbiota, require further detailed investigation. This review categorizes anticancer gut bacteria according to their effects on cancer cells and elucidates their anticancer mechanisms across five domains: modification of the tumor microenvironment, competitive inhibition, activation of immune cells, vectors for gene therapy, and production of bacterial anticancer biomolecules. Additionally, we discuss the potential challenges of utilizing different gut bacteria for cancer treatment, highlight their anticancer advantages, and suggest promising directions for future research. Ultimately, this review serves as a comprehensive guide for utilizing both natural and engineered gut bacteria as therapeutic agents against solid tumors in cancer treatment. Full article

A detailed analysis was carried out on the impact of cardiovascular disease on the risk of death of patients hospitalized at a temporary hospital in Gdańsk during the third and fifth waves of the COVID-19 pandemic (in 2021 and 2022, respectively). Background/Objectives: The documentation of 1244 patients was analyzed, of which 701 were hospitalized in 2021 (the Delta variant) and 543 in 2022 (the Omicron variant). The aim of this study was to assess the risk of death of patients with COVID-19 depending on the co-existence of cardiovascular diseases. Methods: A model of logistic regression was used to identify the impact of the patients’ age, the coexistence of cardiovascular disease, and the length of hospitalization on the risk of death. Results: In 2021, patients were younger (median of 66 years) than in 2022 (median of 74 years), the length of hospitalization was shorter in 2022 (9 days) than in 2021 (11 days), and there was a higher proportion of patients with cardiovascular and respiratory diseases and a medical history of cancer in 2022. The odds of death were also observed to be higher in older patients with cardiovascular disease, particularly those under 73 years of age. In older patients (over 73 years), the odds were paradoxically reduced. Conclusions: The age of the patient, cardiovascular disease, and duration of hospitalization affect the risk of death. The Delta variant (2021) was more virulent than Omicron (2022). Cardiovascular disease significantly increases the risk of death in patients with COVID-19. The comprehensive diagnosis and treatment of patients with these conditions may reduce mortality. Further studies are needed on the long-term effects of COVID-19 on the cardiovascular system. Full article

Background: Recent evidence has shown that insulin resistance (IR), a hallmark of nonalcoholic fatty liver disease, predicts bladder cancer (BC) presence. However, the best surrogate marker of IR in predicting BC is still unclear. This study examined the relationships among ten surrogate markers of IR and the presence of BC. Methods: Data from 209 patients admitted to two urology departments from September 2021 to October 2024 were retrospectively analyzed. Individuals (median age 70 years) were divided into two groups (123 and 86 patients, respectively) based on the presence/absence after cystoscopy/TURB of non-metastatic BC. Univariate logistic regression was used to determine the relationships between groups, and the following IR parameters: Triglyceride–Glucose (TyG) index, TyG-BMI, HOMA-IR HOMAB, MetS-IR, Single Point Insulin Sensitivity Estimator, Disposition Index, non-HDL/HDL, TG/HDL-C ratio and Lipoprotein Combine Index. Stepwise logistic regressions were carried out to evaluate the significant predictions and LASSO regression to confirm any significant variable(s). The predictive value of the index test for coexistent BC was evaluated using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). Results: The univariate analysis revealed that the TyG index and MetS-IR were associated with the BC presence. Specifically, the associations of the TyG index and MetS-IR were more significant in participants =/> 65 years old. In multivariate analysis, the stepwise logistic regression, evaluating the most representative variables at univariate analysis, revealed a prediction of BC by only TyG index (OR 2.51, p = 0.012), confirmed by LASSO regression, with an OR of 3.13, p = 0.004). Assessing the diagnostic reliability of TyG, it showed an interesting predictive value for the existence of BC (AUC = 0.60; 95% CI, 0.51–0.68, cut-off 8.50). Additionally, a restricted cubic spline model to fit the dose–response relationship between the values of the index text (TyG) and the BC evidenced the presence of a non-linear association, with a high predictive value of the first knot, corresponding to its 10th percentile. The decision curve analysis confirmed that the model (TyG) has utility in supporting clinical decisions. Conclusions: Compared to other surrogate markers of IR, the TyG index is effective in identifying individuals at risk for BC. A TyG threshold of 8.5 was highly sensitive for detecting BC subjects and may be suitable as an auxiliary diagnostic criterion for BC in adults, mainly if less than 65 years old. Full article

Candida species, particularly Candida albicans, are causative agents of oral infections to which immunocompromised patients are especially susceptible. Reduced saliva flow (xerostomia) can lead to Candida overgrowth, as saliva contains antibacterial components such as histatins and β-defensins that inhibit fungal growth and adhesion to the oral mucosa. Candida adheres to host tissues, forms biofilms, and secretes enzymes required for tissue invasion and immune evasion. Secretory asparaginyl proteinases (Saps) and candidalysin, a cytolytic peptide toxin, are vital to Candida virulence, and agglutinin-like sequence (Als) proteins are crucial for adhesion, invasion, and biofilm formation. C. albicans is a risk factor for dental caries and may increase periodontal disease virulence when it coexists with Porphyromonas gingivalis. Candida infections have been suggested to heighten the risk of oral cancer based on a relationship between Candida species and oral squamous cell carcinoma (OSCC) or oral potentially malignant disorder (OPMD). Meanwhile, β-glucan in the Candida cell wall has antitumor effects. In addition, Candida biofilms protect viruses such as herpesviruses and coxsackieviruses. Understanding the intricate interactions between Candida species, host immune responses, and coexisting microbial communities is essential for developing preventive and therapeutic strategies against oral Candida infections, particularly in immunocompromised individuals. Full article

South Africa has the highest HIV prevalence globally, often co-occurring with helminth infections in impoverished regions. The coexistence of these infections leads to immunological interactions, potentially enhancing oncogenesis by upregulating immune checkpoint molecules (ICs) among other effects. Notably, most ICs are overexpressed in cancer and correlated with its progression. Helminth infections trigger Th2-type immunity, increasing immunosuppressive M2 macrophages, regulatory T cells, and associated IC molecules. PD-L2 is reported to contribute to Th2-type immunity induced by helminth infections. Similarly, TIM-3, elevated during chronic viral infections, induces a similar immunosuppressive profile. CTLA-4 and PD-1 impact T-cell function by interacting with CD28, crucial for T-cell function. CD28 is downregulated in chronic infections and cancer. This study investigated the impact of HIV-helminth co-infection on co-stimulatory and co-inhibitory molecule profiles associated with antitumor immunity. Using 78 serum samples collected from March 2020 to May 2021, participants were categorized into uninfected control (no HIV and helminth infections), HIV-infected, helminth-infected, and HIV-helminth co-infected groups. Multiplex immune regulatory molecule assay analysis was conducted. The data were analyzed using multivariate regression analysis and adjusted for confounders (age, gender, BMI, ART, supplements, and other chronic diseases). The uninfected control group was used as the baseline reference group for analysis. HIV-infected individuals had higher PD-1 (adjusted β = 0.12, p = 0.034) and TIM-3 (adjusted β = 23.15, p = 0.052) levels, with the latter showing a trend toward significance. However, lower CD28 levels (adjusted β = −651.95, p = 0.010) were observed. Helminth-infected individuals had higher TIM-3 levels (adjusted β = 20.98, p = 0.020). The co-infected group had higher PD-1 (unadjusted β = 0.18, p = 0.0046) and PD-L2 (adjusted β = 7.95, p = 0.033) levels. A significant decrease in CD28 profile was observed across all infected groups: HIV-infected (adjusted β = −651.95, p = 0.010), helminth-infected (adjusted β = −674.32, p = 0.001), and co-infected (adjusted β = −671.55, p = 0.044). The results suggest that HIV-helminth co-infections alter immune checkpoint markers, potentially increasing cancer risk by promoting an immunosuppressive microenvironment that hinders anti-cancer immunity. CD28’s downregulation underscores immune inefficiency in chronic diseases. Addressing these co-infections is crucial for improving HIV care and potentially reducing cancer risks through targeted strategies. Full article

Background: This case report describes the rare coexistence of cervical cancer with pregnancy, a challenging scenario requiring careful balance between maternal treatment and fetal safety. In Poland, cervical cancer remains a significant health issue, highlighting the need for effective multidisciplinary strategies. Methods: This case report was prepared based on CARE guidelines for medical case reporting. The patient was observed by a clinical psycho-oncologist–midwife and a psychologist (also specializing in clinical psycho-oncology) from the start of oncological treatment until delivery and early postpartum. During pregnancy, the pregnant woman was asked three times (at the 23rd, 32nd, and 38th weeks of pregnancy) to complete questionnaires: a self-report questionnaire collecting sociodemographic data, clinical information, and perception of causes and effects of fatigue, the Chalder Fatigue Questionnaire (CHFQ-PL), the Fatigue Management Barriers Questionnaire (FMBQ), the Multidimensional Social Support Scale (MSPSS), and the Walsh Family Resilience Questionnaire (WFRQ-PL). Results: The patient, a 37-year-old woman in her second pregnancy, presented with cervical cancer diagnosed in the first trimester. Major concerns included fatigue, emotional distress, and treatment-related uncertainties. Throughout the pregnancy, she underwent four chemotherapy cycles and participated in psycho-oncological assessments to monitor fatigue, which increased as treatment progressed and affected daily functioning and emotional well-being. To enable the early continuation of oncology treatment, the pregnancy was electively terminated by cesarean section at 37+5 weeks, resulting in the good condition of the infant and a stable maternal postpartum condition, though anemia and emotional concerns required further management. Conclusions: As research on fatigue in pregnant oncology patients is limited, this case underscores the value of structured psycho-oncological support to enhance care and outcomes for both mother and child. Full article

Background: Parathyroid cancers are rare endocrine malignancies that pose diagnostic and therapeutic challenges, particularly when discovered incidentally or in the presence of multiple endocrine disorders. This study aims to provide clinical, biochemical and pathological insights into these malignancies through a retrospective case series. Methods: We analyzed retrospectively, from a tertiary and an endocrine surgery referral center, 13 cases of parathyroid cancers, where 4 cases were associated with thyroid cancers, including demographic data, clinical presentation, biochemical markers, imaging, surgical interventions, histopathological findings and follow-up outcomes. Descriptive statistics were used to summarize patient characteristics. Results: The median age of the cohort was 64 (range: 40–81 years), with a female-to-male ratio of 8:5. More than half of the cases (61.53%) were diagnosed incidentally, with common biochemical findings including elevated parathyroid hormone (PTH) levels (median: 430 pg/mL) and hypercalcemia in 80% of the patients. All patients underwent surgery, with parathyroid resections with concomitant total thyroidectomy (62%) or lobectomy (23%) as the most common interventions. Histopathological analysis confirmed parathyroid carcinoma in all cases, with coexisting thyroid malignancies observed in 31%. An immunohistochemical profile performed in about half of the patients was in accordance with previously published data. Postoperative normalization of PTH levels was achieved in 77% of patients, and no recurrence or metastasis was observed in 85% of cases during follow-up. Conclusions: Despite the exceptional rarity of the disease, this case series highlights the importance of preoperative biochemical and imaging evaluation and the efficacy of surgical management. Long-term outcomes remain favorable with early diagnosis and diligent postoperative monitoring. Further research into molecular biomarkers and targeted therapies is warranted to improve the management of advanced or recurrent disease. Full article

Background: Aging is characterized by shared cellular and molecular processes, and aging-related diseases might co-exist in a cluster of comorbidities, particularly in vulnerable individuals whose phenotype meets the criteria for frailty. Whilst the multidimensional definition of frailty is still controversial, there is an increasing understanding of the common pathways linking metabolic syndrome, cognitive decline, and sarcopenia, frequent conditions in frail elderly patients. Methods: We performed a systematic search in the electronic databases Cochrane Library and PubMed and included preclinical studies, cohort and observational studies, and trials. Discussion: Metabolic syndrome markers, such as insulin resistance and the triglyceride/HDL C ratio, correlate with early cognitive impairment. Insulin resistance is a cause of synaptic dysfunction and neurodegeneration. Conversely, fasting and fasting-mimicking agents promote neuronal resilience by enhancing mitochondrial efficiency, autophagy, and neurogenesis. Proteins acting as cellular metabolic sensors, such as SIRT1, play a pivotal role in aging, neuroprotection, and metabolic health. In AD, β-amyloid accumulation and hyperphosphorylated tau in neurofibrillary tangles can cause metabolic reprogramming in brain cells, shifting from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect in cancer. The interrelation of metabolic syndrome, sarcopenia, and cognitive decline suggests that targeting these shared metabolic pathways could mitigate all the conditions. Pharmacological interventions, including GLP-1 receptor agonists, metformin, and SIRT 1 inducers, demonstrated neuroprotective effects in animals and some preliminary clinical models. Conclusions: These findings encourage further research on the prevention and treatment of neurodegenerative diseases as well as the drug-repurposing potential of molecules currently approved for diabetes, dyslipidemia, and metabolic syndrome. Full article