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Background:
Targeted radioligand therapy (TRT) is an emerging theranostic modality in oncology. While well established in neuroendocrine and prostate cancers, its role in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) remains investigational. This systematic review summarizes current evidence evaluating TRT in lung cancer.
Methods:
A Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-guided systematic review of PubMed, Embase, and Scopus (2000–November 2025) was conducted. Original studies evaluating TRT in SCLC or NSCLC were included. Primary outcomes were tumor response, disease-control rate, and treatment-related toxicity. Secondary outcomes included progression-free survival, overall survival, and dosimetry. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I) tool.
Results:
From 2,453 records, 15 studies were included, reporting 358 lung cancer patients, of whom 105 received TRT. Disease-control rates reached up to 78% in mixed NSCLC/SCLC cohorts. In SCLC, somatostatin receptor-targeted peptide receptor radionuclide therapy demonstrated heterogeneous disease control (0–50%), with [177Lu]Lu-labeled agents showing more favorable outcomes than [90Y]Y-based therapy. The most favorable outcomes were a median progression-free survival of 11.9 months and an overall survival of 16 months in responders. In NSCLC, fibroblast activation protein (FAP)-targeted agents such as [177Lu]Lu-FAP-2286 demonstrated partial metabolic responses, including a 44.4% response rate and 78% disease control in a mixed cohort. Severe toxicities were infrequent.
Discussion:
TRT is a promising but experimental option for advanced lung cancer. Early efficacy signals exist for strong somatostatin receptor (SSTR)-targeted therapy in SCLC and FAP-targeted therapy in NSCLC, but evidence remains limited. Prospective trials with standardized protocols and dosimetry are needed to define TRT’s role in lung cancer treatment.
Background:
Targeted radioligand therapy (TRT) is an emerging theranostic modality in oncology. While well established in neuroendocrine and prostate cancers, its role in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) remains investigational. This systematic review summarizes current evidence evaluating TRT in lung cancer.
Methods:
A Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-guided systematic review of PubMed, Embase, and Scopus (2000–November 2025) was conducted. Original studies evaluating TRT in SCLC or NSCLC were included. Primary outcomes were tumor response, disease-control rate, and treatment-related toxicity. Secondary outcomes included progression-free survival, overall survival, and dosimetry. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I) tool.
Results:
From 2,453 records, 15 studies were included, reporting 358 lung cancer patients, of whom 105 received TRT. Disease-control rates reached up to 78% in mixed NSCLC/SCLC cohorts. In SCLC, somatostatin receptor-targeted peptide receptor radionuclide therapy demonstrated heterogeneous disease control (0–50%), with [177Lu]Lu-labeled agents showing more favorable outcomes than [90Y]Y-based therapy. The most favorable outcomes were a median progression-free survival of 11.9 months and an overall survival of 16 months in responders. In NSCLC, fibroblast activation protein (FAP)-targeted agents such as [177Lu]Lu-FAP-2286 demonstrated partial metabolic responses, including a 44.4% response rate and 78% disease control in a mixed cohort. Severe toxicities were infrequent.
Discussion:
TRT is a promising but experimental option for advanced lung cancer. Early efficacy signals exist for strong somatostatin receptor (SSTR)-targeted therapy in SCLC and FAP-targeted therapy in NSCLC, but evidence remains limited. Prospective trials with standardized protocols and dosimetry are needed to define TRT’s role in lung cancer treatment.
DOI: https://doi.org/10.37349/etat.2026.1002368
Aim:
Redox-oxidative dysregulation is implicated in the aetiology of several diseases, including schizophrenia, with a possible influence on clinical symptoms. This study investigated the influence of redox, lipid peroxidation, and micronutrient antioxidants on the expression of clinical phenotypes of schizophrenia.
Methods:
A total of 220 consenting drug-naïve volunteers, including 120 participants with schizophrenia and 100 apparently healthy controls, were recruited. Schizophrenia symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Lipid peroxidation (malondialdehyde; MDA) was quantified using the thiobarbituric acid reactive substances (TBARS) spectrophotometric method; glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were assessed using established enzymatic activity assays; total antioxidant capacity (TAC) was determined by the phosphomolybdenum colorimetric method; vitamins C and E were measured using spectrophotometric biochemical assays; and zinc (Zn) and selenium (Se) concentrations were quantified using atomic absorption spectrophotometry (AAS).
Results:
Enzymatic antioxidants, SOD (19.58 ± 0.80; 10.12 ± 0.45 U/L) and CAT (41.73 ± 1.81; 21.33 ± 0.98 U/L), increased in schizophrenia compared with controls (p < 0.05), but decreased non-enzymatic antioxidants; GSH (14.5 ± 0.28; 15.9 ± 1.59 µmol/L, p < 0.05). Furthermore, serum levels of zinc (1.8 ± 0.01; 2.7 ± 0.02 mg/L), selenium (0.08 ± 0.01; 0.10 ± 0.01 mg/L), and vitamin C (12.98 ± 0.49; 15.08 ± 0.37 mg/L) were lowered in schizophrenia compared with controls (p < 0.05). GSH had a negative correlation with positive symptoms (r = –0.285, p = 0.013) while SOD (r = 0.281, p = 0.001) and CAT (r = 0.179, p = 0.034) correlated positively with MDA (p < 0.05). In contrast, GSH (r = –0.247, p = 0.003) and TAC (r = –0.221, p = 0.009) correlated negatively with MDA (p < 0.05).
Conclusions:
Drug-naïve Nigerian individuals with schizophrenia appear to exhibit a pattern of redox imbalance, including increased lipid peroxidation, altered antioxidant enzyme activity, and reduced non-enzymatic antioxidants, with lower GSH levels modestly associated with greater positive symptom severity.
Aim:
Redox-oxidative dysregulation is implicated in the aetiology of several diseases, including schizophrenia, with a possible influence on clinical symptoms. This study investigated the influence of redox, lipid peroxidation, and micronutrient antioxidants on the expression of clinical phenotypes of schizophrenia.
Methods:
A total of 220 consenting drug-naïve volunteers, including 120 participants with schizophrenia and 100 apparently healthy controls, were recruited. Schizophrenia symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Lipid peroxidation (malondialdehyde; MDA) was quantified using the thiobarbituric acid reactive substances (TBARS) spectrophotometric method; glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were assessed using established enzymatic activity assays; total antioxidant capacity (TAC) was determined by the phosphomolybdenum colorimetric method; vitamins C and E were measured using spectrophotometric biochemical assays; and zinc (Zn) and selenium (Se) concentrations were quantified using atomic absorption spectrophotometry (AAS).
Results:
Enzymatic antioxidants, SOD (19.58 ± 0.80; 10.12 ± 0.45 U/L) and CAT (41.73 ± 1.81; 21.33 ± 0.98 U/L), increased in schizophrenia compared with controls (p < 0.05), but decreased non-enzymatic antioxidants; GSH (14.5 ± 0.28; 15.9 ± 1.59 µmol/L, p < 0.05). Furthermore, serum levels of zinc (1.8 ± 0.01; 2.7 ± 0.02 mg/L), selenium (0.08 ± 0.01; 0.10 ± 0.01 mg/L), and vitamin C (12.98 ± 0.49; 15.08 ± 0.37 mg/L) were lowered in schizophrenia compared with controls (p < 0.05). GSH had a negative correlation with positive symptoms (r = –0.285, p = 0.013) while SOD (r = 0.281, p = 0.001) and CAT (r = 0.179, p = 0.034) correlated positively with MDA (p < 0.05). In contrast, GSH (r = –0.247, p = 0.003) and TAC (r = –0.221, p = 0.009) correlated negatively with MDA (p < 0.05).
Conclusions:
Drug-naïve Nigerian individuals with schizophrenia appear to exhibit a pattern of redox imbalance, including increased lipid peroxidation, altered antioxidant enzyme activity, and reduced non-enzymatic antioxidants, with lower GSH levels modestly associated with greater positive symptom severity.
DOI: https://doi.org/10.37349/en.2026.1006134
This commentary discusses the FDA’s drug approvals in 2025, with a particular focus on cancer therapies and the role of companion diagnostics (CDx). Cancer has emerged as the leading therapeutic area, accounting for 35% of all new drug approvals, largely driven by targeted therapies, with kinase inhibitors representing nearly half of these drugs. Many of the drugs have received orphan drug designations and/or have utilized the Accelerated Approval Program. A key finding was the widespread adoption of the drug-diagnostic co-development model, in which a CDx assay is developed along with the drug and used for patient selection in clinical trials. However, a significant challenge is the frequent lack of concurrent drug and CDx assay approvals. The absence of an analytically and clinically validated CDx assay may pose a challenge for healthcare providers in accurately identifying eligible patients, potentially delaying access to appropriate therapy. The FDA’s cancer drug approvals for 2025 highlight an ongoing commitment to precision medicine, with several new targeted treatments, such as antibody-drug conjugates and kinase inhibitors, where CDx assays play an important role in identifying the appropriate patient population.
This commentary discusses the FDA’s drug approvals in 2025, with a particular focus on cancer therapies and the role of companion diagnostics (CDx). Cancer has emerged as the leading therapeutic area, accounting for 35% of all new drug approvals, largely driven by targeted therapies, with kinase inhibitors representing nearly half of these drugs. Many of the drugs have received orphan drug designations and/or have utilized the Accelerated Approval Program. A key finding was the widespread adoption of the drug-diagnostic co-development model, in which a CDx assay is developed along with the drug and used for patient selection in clinical trials. However, a significant challenge is the frequent lack of concurrent drug and CDx assay approvals. The absence of an analytically and clinically validated CDx assay may pose a challenge for healthcare providers in accurately identifying eligible patients, potentially delaying access to appropriate therapy. The FDA’s cancer drug approvals for 2025 highlight an ongoing commitment to precision medicine, with several new targeted treatments, such as antibody-drug conjugates and kinase inhibitors, where CDx assays play an important role in identifying the appropriate patient population.
DOI: https://doi.org/10.37349/etat.2026.1002369
This article belongs to the special issue Precision Oncology: Molecular Classification, Efficacy Prediction, and Treatment Decision-Making
Aim:
Stroke represents a leading cause of mortality and disability globally, yet comprehensive epidemiological analyses for Saudi Arabia remain limited. This study aimed to analyze temporal trends in stroke incidence, mortality, and disability-adjusted life years (DALYs) in Saudi Arabia from 1990 to 2021, examine stroke subtype distributions and risk factor attributions, and compare findings with regional and international benchmarks.
Methods:
We conducted a comprehensive analysis of the Global Burden of Disease (GBD) 2021 study data for Saudi Arabia, supplemented by systematic review findings and hospital-based registry data. Age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates were extracted for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Annual percent change (APC) was calculated using Joinpoint regression. Risk factor attribution was analyzed using comparative risk assessment methodology. Poisson regression models examined sex differences.
Results:
The pooled annual stroke incidence in Saudi Arabia was 29 per 100,000 population (95% CI: 15–47). Ischemic stroke predominated, comprising 79–87% of cases. Age-standardized DALYs showed significant yearly decreases of 9.28 per 100,000 (95% CI: 6.31–12.26, p < 0.001). The age-standardized death rate in the Middle East and North Africa (MENA) region was 87.7 per 100,000 [95% uncertainty interval (UI): 78.2–97.6] in 2019, representing a 27.8% regional decrease from 1990. Mean age at first stroke in Saudi Arabia was 63 years—six years younger than Western populations. Hypertension (57.7%), diabetes mellitus (49.4%), and obesity (42.0%) were the major modifiable risk factors. Intravenous thrombolysis utilization remained critically low at 1–3.6%.
Conclusions:
Despite declining mortality and DALYs, Saudi Arabia faces a substantial stroke burden characterized by a younger onset age and significant treatment gaps. Achieving Vision 2030 health targets requires accelerated primary prevention addressing metabolic risk factors and expansion of acute stroke treatment capacity nationwide.
Aim:
Stroke represents a leading cause of mortality and disability globally, yet comprehensive epidemiological analyses for Saudi Arabia remain limited. This study aimed to analyze temporal trends in stroke incidence, mortality, and disability-adjusted life years (DALYs) in Saudi Arabia from 1990 to 2021, examine stroke subtype distributions and risk factor attributions, and compare findings with regional and international benchmarks.
Methods:
We conducted a comprehensive analysis of the Global Burden of Disease (GBD) 2021 study data for Saudi Arabia, supplemented by systematic review findings and hospital-based registry data. Age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates were extracted for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Annual percent change (APC) was calculated using Joinpoint regression. Risk factor attribution was analyzed using comparative risk assessment methodology. Poisson regression models examined sex differences.
Results:
The pooled annual stroke incidence in Saudi Arabia was 29 per 100,000 population (95% CI: 15–47). Ischemic stroke predominated, comprising 79–87% of cases. Age-standardized DALYs showed significant yearly decreases of 9.28 per 100,000 (95% CI: 6.31–12.26, p < 0.001). The age-standardized death rate in the Middle East and North Africa (MENA) region was 87.7 per 100,000 [95% uncertainty interval (UI): 78.2–97.6] in 2019, representing a 27.8% regional decrease from 1990. Mean age at first stroke in Saudi Arabia was 63 years—six years younger than Western populations. Hypertension (57.7%), diabetes mellitus (49.4%), and obesity (42.0%) were the major modifiable risk factors. Intravenous thrombolysis utilization remained critically low at 1–3.6%.
Conclusions:
Despite declining mortality and DALYs, Saudi Arabia faces a substantial stroke burden characterized by a younger onset age and significant treatment gaps. Achieving Vision 2030 health targets requires accelerated primary prevention addressing metabolic risk factors and expansion of acute stroke treatment capacity nationwide.
DOI: https://doi.org/10.37349/en.2026.1006135
This article belongs to the special issue The Science of Ischemic Stroke
Aim:
This study aims to explore the role of the hashtag #EndoTwitter on the social media platform X by examining its geographical distribution, user demographics, engagement patterns, and post sentiments. With the increasing prevalence of endocrine and metabolic diseases, rapid knowledge exchange is essential. #EndoTwitter provides a unique communication medium for healthcare professionals, researchers, advocacy groups, journalists, and patients; however, its impact has not yet been systematically studied.
Methods:
The Fedica research analytics tool was used to analyze X posts containing #EndoTwitter from July 1, 2019, to July 1, 2023. Parameters assessed included post volume, impressions, sentiment, co-occurring hashtags, and geolocation.
Results:
A total of 58,392 posts with #EndoTwitter were retrieved from around 21,000 users, generating 46.9 million impressions. These posts originated mainly from the United States (N = 29,546, 50.6%), followed by India (N = 6,567, 11.2%) and Mexico (N = 3,310, 5.7%). The top co-occurring hashtags included #MedTwitter, #Diabetes, and #NAFLD. Sentiment analysis revealed 16% positive sentiment, 8% negative, and 76% neutral among all posts.
Conclusions:
#EndoTwitter has the potential to foster evidence-based information sharing and inclusive communities, making it a valuable tool for endocrinology advocacy and patient care. Future research should explore specific post content to deepen insights into its impact.
Aim:
This study aims to explore the role of the hashtag #EndoTwitter on the social media platform X by examining its geographical distribution, user demographics, engagement patterns, and post sentiments. With the increasing prevalence of endocrine and metabolic diseases, rapid knowledge exchange is essential. #EndoTwitter provides a unique communication medium for healthcare professionals, researchers, advocacy groups, journalists, and patients; however, its impact has not yet been systematically studied.
Methods:
The Fedica research analytics tool was used to analyze X posts containing #EndoTwitter from July 1, 2019, to July 1, 2023. Parameters assessed included post volume, impressions, sentiment, co-occurring hashtags, and geolocation.
Results:
A total of 58,392 posts with #EndoTwitter were retrieved from around 21,000 users, generating 46.9 million impressions. These posts originated mainly from the United States (N = 29,546, 50.6%), followed by India (N = 6,567, 11.2%) and Mexico (N = 3,310, 5.7%). The top co-occurring hashtags included #MedTwitter, #Diabetes, and #NAFLD. Sentiment analysis revealed 16% positive sentiment, 8% negative, and 76% neutral among all posts.
Conclusions:
#EndoTwitter has the potential to foster evidence-based information sharing and inclusive communities, making it a valuable tool for endocrinology advocacy and patient care. Future research should explore specific post content to deepen insights into its impact.
DOI: https://doi.org/10.37349/edht.2026.101192
Janus kinase (JAK) inhibitors represent a major advancement in the management of immune-mediated inflammatory diseases. A balanced approach that carefully weighs therapeutic benefits against potential risks is essential. Through appropriate patient selection, close monitoring, and open physician–patient communication, the clinical potential of JAK inhibitors can be optimized while minimizing adverse outcomes. Nine JAK inhibitors have demonstrated utility in hepatogastrointestinal disorders; however, only two have FDA approval. JAK inhibitors are classified into reversible (competitive) and irreversible (covalent) inhibitors according to their chemical binding with amino acids. This review discusses the safety profile, adverse effects, and molecular selectivity of JAK inhibitors, and highlights their therapeutic roles in hepatogastrointestinal diseases, including inflammatory bowel disease, hepatic fibrosis, hepatocellular carcinoma, autoimmune diseases associated with cancer therapy in post-transplant patients, eosinophilic esophagitis, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease, and acute graft-versus-host disease following liver transplantation.
Janus kinase (JAK) inhibitors represent a major advancement in the management of immune-mediated inflammatory diseases. A balanced approach that carefully weighs therapeutic benefits against potential risks is essential. Through appropriate patient selection, close monitoring, and open physician–patient communication, the clinical potential of JAK inhibitors can be optimized while minimizing adverse outcomes. Nine JAK inhibitors have demonstrated utility in hepatogastrointestinal disorders; however, only two have FDA approval. JAK inhibitors are classified into reversible (competitive) and irreversible (covalent) inhibitors according to their chemical binding with amino acids. This review discusses the safety profile, adverse effects, and molecular selectivity of JAK inhibitors, and highlights their therapeutic roles in hepatogastrointestinal diseases, including inflammatory bowel disease, hepatic fibrosis, hepatocellular carcinoma, autoimmune diseases associated with cancer therapy in post-transplant patients, eosinophilic esophagitis, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease, and acute graft-versus-host disease following liver transplantation.
DOI: https://doi.org/10.37349/edd.2026.1005122
This study aimed to characterize and quantify essential and potentially toxic elements in commonly consumed spices in order to evaluate their nutritional value and assess possible food-safety risks related to metal contamination. Four spices: fenugreek (Trigonella foenum-graecum), black pepper (Piper nigrum), turmeric (Curcuma longa), and ginger (Zingiber officinale) were collected from a supermarket in Mehdia (Kenitra, Morocco). Samples were homogenized, sieved (< 250 μm), and digested using a nitric/perchloric acid mixture (3:1, v/v) following AOAC Method 999.10. Sixteen elements were determined using high-resolution inductively coupled plasma mass spectrometry (ICP-MS). Quality assurance was ensured through the use of blanks, duplicate analyses, and certified reference material (NIST SRM 1573a). The results revealed significant elemental variability among the spices: ginger showed the highest sodium and manganese levels, turmeric was rich in potassium and magnesium, black pepper exhibited elevated calcium, and fenugreek contained high phosphorus concentrations. Lead was detected in all samples (3.60–15.90 μg/kg), remaining below Codex Alimentarius limits. Overall, the findings demonstrate the reliability of ICP-MS for ultra-trace elemental analysis in spices and confirm their dual nutritional and toxicological relevance. Although toxic metal levels were within regulatory limits, continuous monitoring and strengthened safety controls are recommended to minimize potential health risks.
This study aimed to characterize and quantify essential and potentially toxic elements in commonly consumed spices in order to evaluate their nutritional value and assess possible food-safety risks related to metal contamination. Four spices: fenugreek (Trigonella foenum-graecum), black pepper (Piper nigrum), turmeric (Curcuma longa), and ginger (Zingiber officinale) were collected from a supermarket in Mehdia (Kenitra, Morocco). Samples were homogenized, sieved (< 250 μm), and digested using a nitric/perchloric acid mixture (3:1, v/v) following AOAC Method 999.10. Sixteen elements were determined using high-resolution inductively coupled plasma mass spectrometry (ICP-MS). Quality assurance was ensured through the use of blanks, duplicate analyses, and certified reference material (NIST SRM 1573a). The results revealed significant elemental variability among the spices: ginger showed the highest sodium and manganese levels, turmeric was rich in potassium and magnesium, black pepper exhibited elevated calcium, and fenugreek contained high phosphorus concentrations. Lead was detected in all samples (3.60–15.90 μg/kg), remaining below Codex Alimentarius limits. Overall, the findings demonstrate the reliability of ICP-MS for ultra-trace elemental analysis in spices and confirm their dual nutritional and toxicological relevance. Although toxic metal levels were within regulatory limits, continuous monitoring and strengthened safety controls are recommended to minimize potential health risks.
DOI: https://doi.org/10.37349/eff.2026.1010139
High-sensitivity cardiac biomarkers have transformed modern cardiology by enabling earlier diagnosis and refined risk stratification in acute coronary syndromes and heart failure. However, increasing analytical sensitivity has also amplified the clinical impact of immunoassay interferences, particularly those caused by heterophile antibodies. These endogenous antibodies can interact with assay antibodies and generate false-positive or false-negative results, most notably in sandwich immunoassays used for cardiac troponins and natriuretic peptides. Persistent, clinically implausible biomarker elevations related to heterophile antibody interference have led to unnecessary invasive procedures, inappropriate pharmacologic treatment, repeated hospital admissions, and prolonged diagnostic uncertainty. Conversely, false-negative results may delay diagnosis, result in inappropriate discharge, and contribute to adverse clinical outcomes in high-risk patients. This review summarizes the immunological basis and analytical mechanisms of heterophile antibody interference, highlights cardiac biomarkers most commonly affected, and outlines key clinical red flags that should prompt suspicion. Practical laboratory strategies include polyethylene glycol precipitation as an initial approach to detect antibody-mediated interference, followed by dilution studies, heterophile blocking reagents, and cautiously interpreted alternative platform testing within assay-specific reference frameworks, together with close clinician-laboratory collaboration. Greater awareness of analytical interference is critical as cardiology becomes increasingly biomarker-driven. Integrating clinical judgment with structured laboratory verification can substantially reduce diagnostic error, improve patient safety, and prevent avoidable healthcare utilization in contemporary cardiovascular practice.
High-sensitivity cardiac biomarkers have transformed modern cardiology by enabling earlier diagnosis and refined risk stratification in acute coronary syndromes and heart failure. However, increasing analytical sensitivity has also amplified the clinical impact of immunoassay interferences, particularly those caused by heterophile antibodies. These endogenous antibodies can interact with assay antibodies and generate false-positive or false-negative results, most notably in sandwich immunoassays used for cardiac troponins and natriuretic peptides. Persistent, clinically implausible biomarker elevations related to heterophile antibody interference have led to unnecessary invasive procedures, inappropriate pharmacologic treatment, repeated hospital admissions, and prolonged diagnostic uncertainty. Conversely, false-negative results may delay diagnosis, result in inappropriate discharge, and contribute to adverse clinical outcomes in high-risk patients. This review summarizes the immunological basis and analytical mechanisms of heterophile antibody interference, highlights cardiac biomarkers most commonly affected, and outlines key clinical red flags that should prompt suspicion. Practical laboratory strategies include polyethylene glycol precipitation as an initial approach to detect antibody-mediated interference, followed by dilution studies, heterophile blocking reagents, and cautiously interpreted alternative platform testing within assay-specific reference frameworks, together with close clinician-laboratory collaboration. Greater awareness of analytical interference is critical as cardiology becomes increasingly biomarker-driven. Integrating clinical judgment with structured laboratory verification can substantially reduce diagnostic error, improve patient safety, and prevent avoidable healthcare utilization in contemporary cardiovascular practice.
DOI: https://doi.org/10.37349/ec.2026.1012105
Aim:
Pneumonia is the leading cause of morbidity and mortality among elderly individuals. This has led to the search for reliable tools such as inflammatory biomarkers, including C-reactive protein (CRP), procalcitonin (PCT), and neutrophil-to-lymphocyte ratio (NLR), to predict disease severity and prognosis. However, the prognostic value of inflammatory biomarkers in elderly women is not fully understood, as the population is often underrepresented in clinical studies.
Methods:
This retrospective study was conducted at Wahidin Sudirohusodo Hospital, Indonesia. The samples used were elderly women aged ≥ 60 years who were hospitalized with community-acquired pneumonia (CAP) between January and December 2023. CRP, PCT, and NLR levels collected within 24 hours of admission were evaluated and correlated with pneumonia severity index (PSI) scores and in-hospital mortality (IHM). Subsequently, receiver operating characteristic (ROC) curve analysis, logistic regression, and Kaplan-Meier survival analysis were performed.
Results:
A total of 262 patients (median age 66 years) were included, of whom 83.2% had mild CAP, and 87.0% survived. Among inflammatory biomarkers, CRP showed the highest, with limited discriminatory ability for mortality [area under the curve (AUC) 0.543], followed by NLR (AUC 0.495), and PCT (AUC 0.466). All markers had high sensitivity (91.2%) but low specificity, and CRP ≥ 14.5 mg/L was significantly associated with reduced survival (p = 0.018).
Conclusions:
CRP shows a modest prognostic value in predicting mortality among elderly women with CAP, while NLR and PCT have limited utility. These results show the need for gender- and age-specific studies to improve risk stratification and outcomes in the vulnerable population.
Aim:
Pneumonia is the leading cause of morbidity and mortality among elderly individuals. This has led to the search for reliable tools such as inflammatory biomarkers, including C-reactive protein (CRP), procalcitonin (PCT), and neutrophil-to-lymphocyte ratio (NLR), to predict disease severity and prognosis. However, the prognostic value of inflammatory biomarkers in elderly women is not fully understood, as the population is often underrepresented in clinical studies.
Methods:
This retrospective study was conducted at Wahidin Sudirohusodo Hospital, Indonesia. The samples used were elderly women aged ≥ 60 years who were hospitalized with community-acquired pneumonia (CAP) between January and December 2023. CRP, PCT, and NLR levels collected within 24 hours of admission were evaluated and correlated with pneumonia severity index (PSI) scores and in-hospital mortality (IHM). Subsequently, receiver operating characteristic (ROC) curve analysis, logistic regression, and Kaplan-Meier survival analysis were performed.
Results:
A total of 262 patients (median age 66 years) were included, of whom 83.2% had mild CAP, and 87.0% survived. Among inflammatory biomarkers, CRP showed the highest, with limited discriminatory ability for mortality [area under the curve (AUC) 0.543], followed by NLR (AUC 0.495), and PCT (AUC 0.466). All markers had high sensitivity (91.2%) but low specificity, and CRP ≥ 14.5 mg/L was significantly associated with reduced survival (p = 0.018).
Conclusions:
CRP shows a modest prognostic value in predicting mortality among elderly women with CAP, while NLR and PCT have limited utility. These results show the need for gender- and age-specific studies to improve risk stratification and outcomes in the vulnerable population.
DOI: https://doi.org/10.37349/ei.2026.1003250
Implantable cardioverter defibrillators (ICDs) play a central role in the prevention of sudden cardiac death. Although implantation is generally safe, rare but clinically significant complications may occur. One such complication is inadvertent placement of a transvenous ICD lead into the left ventricle via a patent foramen ovale (PFO), which carries a risk of systemic thromboembolism and may remain clinically silent for prolonged periods. We report a case of an ICD lead malpositioned in the left ventricle through a PFO, detected 17 months after implantation during transthoracic echocardiography performed for worsening dyspnoea. Imaging demonstrated the lead traversing the interatrial septum and mitral valve into the left ventricle. The patient underwent successful transvenous extraction and reimplantation of a new right ventricular lead without complications. This case highlights the limitations of electrocardiographic clues alone and underscores the importance of multimodality imaging and meticulous implantation technique. A focused narrative review integrates current literature regarding mechanisms, diagnostic strategies, management options, and preventive considerations.
Implantable cardioverter defibrillators (ICDs) play a central role in the prevention of sudden cardiac death. Although implantation is generally safe, rare but clinically significant complications may occur. One such complication is inadvertent placement of a transvenous ICD lead into the left ventricle via a patent foramen ovale (PFO), which carries a risk of systemic thromboembolism and may remain clinically silent for prolonged periods. We report a case of an ICD lead malpositioned in the left ventricle through a PFO, detected 17 months after implantation during transthoracic echocardiography performed for worsening dyspnoea. Imaging demonstrated the lead traversing the interatrial septum and mitral valve into the left ventricle. The patient underwent successful transvenous extraction and reimplantation of a new right ventricular lead without complications. This case highlights the limitations of electrocardiographic clues alone and underscores the importance of multimodality imaging and meticulous implantation technique. A focused narrative review integrates current literature regarding mechanisms, diagnostic strategies, management options, and preventive considerations.
DOI: https://doi.org/10.37349/ec.2026.1012104
The global rise in consumption of added sugars and confectionery parallels the increasing prevalence of obesity, metabolic dysfunction, and male hypogonadism. Testosterone is essential for male reproductive, metabolic, and cardiovascular health, and growing evidence indicates that excessive sugar intake may disrupt hormonal regulation. This narrative review synthesizes data from human observational and interventional studies and experimental animal models to evaluate the effects of sugar consumption on testosterone homeostasis and male reproductive outcomes. Acute glucose ingestion is associated with hyperinsulinemia and inflammatory cytokine release, which may contribute to transient reductions in circulating testosterone of approximately 20–30%, although findings vary across populations and study designs. Chronic high-sugar intake, particularly from sugar-sweetened beverages, promotes oxidative stress, adiposity, insulin resistance, and leptin dysregulation, which may collectively impair Leydig cell steroidogenesis and contribute to testosterone suppression. Animal studies consistently demonstrate testicular structural damage, downregulation of steroidogenic enzymes, and impaired spermatogenesis under high-sugar dietary conditions. Epidemiological studies associate frequent intake of sugar-sweetened beverages and confectionery with lower testosterone levels and poorer semen parameters. Emerging evidence suggests partial reversibility with dietary interventions emphasizing reduced sugar intake and increased antioxidant consumption. Overall, current data support a biologically plausible link between excessive sugar intake and impaired testosterone regulation, underscoring the need for longitudinal studies and public health strategies targeting added sugar reduction.
The global rise in consumption of added sugars and confectionery parallels the increasing prevalence of obesity, metabolic dysfunction, and male hypogonadism. Testosterone is essential for male reproductive, metabolic, and cardiovascular health, and growing evidence indicates that excessive sugar intake may disrupt hormonal regulation. This narrative review synthesizes data from human observational and interventional studies and experimental animal models to evaluate the effects of sugar consumption on testosterone homeostasis and male reproductive outcomes. Acute glucose ingestion is associated with hyperinsulinemia and inflammatory cytokine release, which may contribute to transient reductions in circulating testosterone of approximately 20–30%, although findings vary across populations and study designs. Chronic high-sugar intake, particularly from sugar-sweetened beverages, promotes oxidative stress, adiposity, insulin resistance, and leptin dysregulation, which may collectively impair Leydig cell steroidogenesis and contribute to testosterone suppression. Animal studies consistently demonstrate testicular structural damage, downregulation of steroidogenic enzymes, and impaired spermatogenesis under high-sugar dietary conditions. Epidemiological studies associate frequent intake of sugar-sweetened beverages and confectionery with lower testosterone levels and poorer semen parameters. Emerging evidence suggests partial reversibility with dietary interventions emphasizing reduced sugar intake and increased antioxidant consumption. Overall, current data support a biologically plausible link between excessive sugar intake and impaired testosterone regulation, underscoring the need for longitudinal studies and public health strategies targeting added sugar reduction.
DOI: https://doi.org/10.37349/eemd.2026.101468
The growing awareness of gluten-related health issues, such as celiac disease, non-celiac gluten sensitivity, and wheat allergies, has led to an increased demand for gluten-free (GF) bread. Producing GF bread, however, presents significant challenges due to the absence of gluten, which plays a crucial role in the texture and structure of traditional bread. Recent research efforts have been directed towards addressing these challenges through the use of alternative ingredients, the adoption of novel processing techniques, and the implementation of quality improvement strategies. This review critically examines the current state of GF bread production, focusing on the difficulties in replicating the properties of conventional bread and exploring various approaches to enhance product quality, including sourdough technology, alternative polymer networks such as arabinoxylans (AXs), enzyme technology, and high hydrostatic pressure (HHP). Key issues include the use of alternative flours, starches, hydrocolloids, enzyme applications, fermentation processes, non-conventional baking and packaging technologies, with particular attention to their impact on sensory and nutritional attributes. The findings suggest that while progress has been made, ongoing research is essential to meet consumer expectations for high-quality GF bread.
The growing awareness of gluten-related health issues, such as celiac disease, non-celiac gluten sensitivity, and wheat allergies, has led to an increased demand for gluten-free (GF) bread. Producing GF bread, however, presents significant challenges due to the absence of gluten, which plays a crucial role in the texture and structure of traditional bread. Recent research efforts have been directed towards addressing these challenges through the use of alternative ingredients, the adoption of novel processing techniques, and the implementation of quality improvement strategies. This review critically examines the current state of GF bread production, focusing on the difficulties in replicating the properties of conventional bread and exploring various approaches to enhance product quality, including sourdough technology, alternative polymer networks such as arabinoxylans (AXs), enzyme technology, and high hydrostatic pressure (HHP). Key issues include the use of alternative flours, starches, hydrocolloids, enzyme applications, fermentation processes, non-conventional baking and packaging technologies, with particular attention to their impact on sensory and nutritional attributes. The findings suggest that while progress has been made, ongoing research is essential to meet consumer expectations for high-quality GF bread.
DOI: https://doi.org/10.37349/eff.2026.1010138
Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that typically arise from the pleura but may occur in various extrathoracic sites. Primary intraparenchymal pulmonary SFTs without pleural attachment are exceptionally uncommon and often pose diagnostic and therapeutic challenges. We report the case of a middle-aged female patient presenting with progressive dyspnea and a large mass in the left lower lobe on imaging. Computed tomography revealed a well-circumscribed, hypervascular mass occupying the left lower lobe. Bronchoscopic and percutaneous biopsies were nondiagnostic, and surgical resection was pursued. Intraoperatively, the tumor was found to arise from the lung parenchyma without pleural involvement. Histopathological examination demonstrated a spindle-cell neoplasm with the typical “patternless pattern,” and immunohistochemistry confirmed nuclear STAT6 positivity, establishing the diagnosis of SFT. The postoperative course was uneventful apart from a transient pulmonary embolism, which was successfully treated. The patient was discharged in good condition and is under regular radiologic surveillance. SFTs of the lung are rare and often mimic more common pulmonary tumors radiologically. Histologic confirmation with STAT6 immunohistochemistry is crucial for accurate diagnosis. Complete surgical excision remains the mainstay of treatment. Given the risk of late recurrence—especially in large tumors—long-term imaging follow-up is mandatory. This case highlights the importance of considering SFT in the differential diagnosis of large pulmonary masses, the critical role of STAT6-based histopathologic confirmation, and the necessity for prolonged surveillance even after complete resection.
Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that typically arise from the pleura but may occur in various extrathoracic sites. Primary intraparenchymal pulmonary SFTs without pleural attachment are exceptionally uncommon and often pose diagnostic and therapeutic challenges. We report the case of a middle-aged female patient presenting with progressive dyspnea and a large mass in the left lower lobe on imaging. Computed tomography revealed a well-circumscribed, hypervascular mass occupying the left lower lobe. Bronchoscopic and percutaneous biopsies were nondiagnostic, and surgical resection was pursued. Intraoperatively, the tumor was found to arise from the lung parenchyma without pleural involvement. Histopathological examination demonstrated a spindle-cell neoplasm with the typical “patternless pattern,” and immunohistochemistry confirmed nuclear STAT6 positivity, establishing the diagnosis of SFT. The postoperative course was uneventful apart from a transient pulmonary embolism, which was successfully treated. The patient was discharged in good condition and is under regular radiologic surveillance. SFTs of the lung are rare and often mimic more common pulmonary tumors radiologically. Histologic confirmation with STAT6 immunohistochemistry is crucial for accurate diagnosis. Complete surgical excision remains the mainstay of treatment. Given the risk of late recurrence—especially in large tumors—long-term imaging follow-up is mandatory. This case highlights the importance of considering SFT in the differential diagnosis of large pulmonary masses, the critical role of STAT6-based histopathologic confirmation, and the necessity for prolonged surveillance even after complete resection.
DOI: https://doi.org/10.37349/etat.2026.1002367
Aim:
This study aimed to investigate how the presence or absence of disulfide bonds affects the antimicrobial activity and thermal stability of pediocin PA-1.
Methods:
To achieve this, the native pediocin peptide and a Cys → Ser mutant lacking the disulfide bridge were evaluated using both in vitro assays and molecular dynamics simulations. Antimicrobial activities of pediocin PA-1 and the mutant peptide were tested at varying temperatures (25–100°C) against selected indicator microorganisms. In parallel, molecular dynamics simulations were performed for both peptides, and RMSD, RMSF, and DSSP analyses were conducted to evaluate structural stability and secondary structure profiles.
Results:
The Cys → Ser mutant peptide exhibited a substantial loss of antimicrobial activity, especially at elevated temperatures, demonstrating the necessity of the disulfide bridge for functional stability. In contrast, pediocin PA-1 retained approximately 96% of its activity even after exposure to 100°C. In silico analyses revealed that while the mutant partially preserved α-helix and β-sheet elements, it displayed pronounced disruption in its three-dimensional conformation.
Conclusions:
The results highlight the critical structural role of Cys residues and disulfide bonds in ensuring both antimicrobial functionality and thermal resilience of pediocin PA-1. These findings provide valuable insights for the rational design of thermally stable antimicrobial peptides for food industry applications.
Aim:
This study aimed to investigate how the presence or absence of disulfide bonds affects the antimicrobial activity and thermal stability of pediocin PA-1.
Methods:
To achieve this, the native pediocin peptide and a Cys → Ser mutant lacking the disulfide bridge were evaluated using both in vitro assays and molecular dynamics simulations. Antimicrobial activities of pediocin PA-1 and the mutant peptide were tested at varying temperatures (25–100°C) against selected indicator microorganisms. In parallel, molecular dynamics simulations were performed for both peptides, and RMSD, RMSF, and DSSP analyses were conducted to evaluate structural stability and secondary structure profiles.
Results:
The Cys → Ser mutant peptide exhibited a substantial loss of antimicrobial activity, especially at elevated temperatures, demonstrating the necessity of the disulfide bridge for functional stability. In contrast, pediocin PA-1 retained approximately 96% of its activity even after exposure to 100°C. In silico analyses revealed that while the mutant partially preserved α-helix and β-sheet elements, it displayed pronounced disruption in its three-dimensional conformation.
Conclusions:
The results highlight the critical structural role of Cys residues and disulfide bonds in ensuring both antimicrobial functionality and thermal resilience of pediocin PA-1. These findings provide valuable insights for the rational design of thermally stable antimicrobial peptides for food industry applications.
DOI: https://doi.org/10.37349/eff.2026.1010137
This article belongs to the special issue Natural Bioactive Compounds in Functional Foods: From Foodomics Insights to Clinical Relevance
Obesity is a determinant of the risk of developing various diseases, including asthma. It can also contribute to asthma severity. Obvious determinants of the risk of developing obesity and conditions associated with obesity are the diet an individual consumes and their energy expenditure, as determined by activity. Therefore, diet and exercise are important non-pharmacological components in the management and prevention of many diseases. Several individual elements in diet, including certain fatty acids and vitamins, as well as types of diets, notably the Mediterranean diet, have been studied in asthmatic patients, but the literature is not consistent. This review explores the relationship between asthma and obesity, exercise, and multiple dietary components and regimens, including the Mediterranean diet; polyunsaturated fats; vitamins A, C, D, and E; flavonoids; probiotics; and sodium intake in the published randomized clinical trials. Overall, the data have many shortcomings, but there is no single component of diet that is consistently associated with improved asthma outcomes, nor any component found to be clearly harmful. However, a diet that helps an individual lose weight may indirectly improve their lung function and asthma control, even if the diet itself does not impact asthma outcomes. Exercise, now known to be safe and widely recommended in asthma, has various forms. This review looked at meta-analyses, as well as recently published data addressing this question, categorizing exercise as aerobic activity, pulmonary rehabilitation, and yoga. The most evidence for benefit is for aerobic exercise, but yoga also has potential for modest improvement in asthma symptoms. There is conflicting data as to whether supervised exercise programs are superior to unsupervised physical activity. Overall, exercise is helpful in asthma, but it is still unclear how much exercise should be done, and this should be tailored to each individual.
Obesity is a determinant of the risk of developing various diseases, including asthma. It can also contribute to asthma severity. Obvious determinants of the risk of developing obesity and conditions associated with obesity are the diet an individual consumes and their energy expenditure, as determined by activity. Therefore, diet and exercise are important non-pharmacological components in the management and prevention of many diseases. Several individual elements in diet, including certain fatty acids and vitamins, as well as types of diets, notably the Mediterranean diet, have been studied in asthmatic patients, but the literature is not consistent. This review explores the relationship between asthma and obesity, exercise, and multiple dietary components and regimens, including the Mediterranean diet; polyunsaturated fats; vitamins A, C, D, and E; flavonoids; probiotics; and sodium intake in the published randomized clinical trials. Overall, the data have many shortcomings, but there is no single component of diet that is consistently associated with improved asthma outcomes, nor any component found to be clearly harmful. However, a diet that helps an individual lose weight may indirectly improve their lung function and asthma control, even if the diet itself does not impact asthma outcomes. Exercise, now known to be safe and widely recommended in asthma, has various forms. This review looked at meta-analyses, as well as recently published data addressing this question, categorizing exercise as aerobic activity, pulmonary rehabilitation, and yoga. The most evidence for benefit is for aerobic exercise, but yoga also has potential for modest improvement in asthma symptoms. There is conflicting data as to whether supervised exercise programs are superior to unsupervised physical activity. Overall, exercise is helpful in asthma, but it is still unclear how much exercise should be done, and this should be tailored to each individual.
DOI: https://doi.org/10.37349/eaa.2026.1009124
This article belongs to the special issue The Complex Interactions Between Lifestyles and Asthma
Aim:
This study aimed to determine the best formulation of gluten-free biscuits made from red rice and cassava composite flour and to evaluate their physicochemical properties, shelf life, and consumer acceptability.
Methods:
Five biscuit formulations (F1: 100:0, F2: 75:25, F3: 50:50, F4: 25:75, F5: 0:100; red rice flour:cassava flour) were prepared. Sensory evaluation using a nine-point hedonic scale identified the optimal formulation. The selected biscuit was further analyzed for proximate composition, dietary fiber, total energy, and physical properties (hardness, color, spread ratio, and bulk density). Shelf life was monitored over eight weeks through microbiological counts, water activity, and texture changes. Consumer acceptance was assessed via a market survey.
Results:
F3 (50:50) achieved the highest scores for color, aroma, taste, crispiness, and overall acceptance. It contained lower moisture (2.87%) and protein (5.45%) but higher ash (0.81%), carbohydrate (72.46%), dietary fiber (3.57%), and energy (474.03 kcal/100 g) than the control (p < 0.05). Fat and crude fiber contents did not differ significantly among the formulations (p > 0.05). F3 showed lower hardness, darker color, higher spread ratio, and greater bulk density. Microbial counts remained at < 10 CFU g⁻1 and water activity ≤ 0.65 during storage, while hardness gradually decreased. Over 70% of consumers rated the product as highly acceptable.
Conclusions:
A 50:50 red rice-cassava formulation produced gluten-free biscuits with favorable nutritional, physical, and sensory qualities and good storage stability, indicating strong potential as a functional snack product.
Aim:
This study aimed to determine the best formulation of gluten-free biscuits made from red rice and cassava composite flour and to evaluate their physicochemical properties, shelf life, and consumer acceptability.
Methods:
Five biscuit formulations (F1: 100:0, F2: 75:25, F3: 50:50, F4: 25:75, F5: 0:100; red rice flour:cassava flour) were prepared. Sensory evaluation using a nine-point hedonic scale identified the optimal formulation. The selected biscuit was further analyzed for proximate composition, dietary fiber, total energy, and physical properties (hardness, color, spread ratio, and bulk density). Shelf life was monitored over eight weeks through microbiological counts, water activity, and texture changes. Consumer acceptance was assessed via a market survey.
Results:
F3 (50:50) achieved the highest scores for color, aroma, taste, crispiness, and overall acceptance. It contained lower moisture (2.87%) and protein (5.45%) but higher ash (0.81%), carbohydrate (72.46%), dietary fiber (3.57%), and energy (474.03 kcal/100 g) than the control (p < 0.05). Fat and crude fiber contents did not differ significantly among the formulations (p > 0.05). F3 showed lower hardness, darker color, higher spread ratio, and greater bulk density. Microbial counts remained at < 10 CFU g⁻1 and water activity ≤ 0.65 during storage, while hardness gradually decreased. Over 70% of consumers rated the product as highly acceptable.
Conclusions:
A 50:50 red rice-cassava formulation produced gluten-free biscuits with favorable nutritional, physical, and sensory qualities and good storage stability, indicating strong potential as a functional snack product.
DOI: https://doi.org/10.37349/eff.2026.1010136
Pollen-related allergic diseases, including allergic rhinoconjunctivitis and asthma, affect a growing proportion of the population and have substantial consequences for quality of life and healthcare systems. Conventional pollen forecasts, which rely on fixed pollen traps and meteorological data, are limited in spatial granularity, real-time responsiveness, and individual relevance. Recent advances in artificial intelligence (AI) and machine learning (ML) offer a paradigm shift in the modelling of pollen release, forecast exposure, and alert allergic patients. This article provides a comprehensive overview of ML-based pollen forecasting systems, clarifying their underlying principles in accessible terms for clinicians and presenting practical and published tools that allergologists can integrate into routine practice. By combining aerobiological data, meteorological models, and patient-reported outcomes, ML enables more personalized, precise, and timely allergy management. We review the fundamental mechanisms of pollen release and dispersion and illustrate how ML models can improve predictive accuracy. Key platforms are compared in terms of clinical usability. We present real-world use cases showing how ML-driven alerts can help optimize treatment plans and support patient education. Practical insights are provided on the evaluation, implementation, and limitations of these tools. ML is not a distant technology—it is already transforming pollen forecasting and allergy alerts. This article aims to equip allergologists with the knowledge needed to evaluate and adopt these tools, enabling a more proactive and personalized approach to managing pollen allergies.
Pollen-related allergic diseases, including allergic rhinoconjunctivitis and asthma, affect a growing proportion of the population and have substantial consequences for quality of life and healthcare systems. Conventional pollen forecasts, which rely on fixed pollen traps and meteorological data, are limited in spatial granularity, real-time responsiveness, and individual relevance. Recent advances in artificial intelligence (AI) and machine learning (ML) offer a paradigm shift in the modelling of pollen release, forecast exposure, and alert allergic patients. This article provides a comprehensive overview of ML-based pollen forecasting systems, clarifying their underlying principles in accessible terms for clinicians and presenting practical and published tools that allergologists can integrate into routine practice. By combining aerobiological data, meteorological models, and patient-reported outcomes, ML enables more personalized, precise, and timely allergy management. We review the fundamental mechanisms of pollen release and dispersion and illustrate how ML models can improve predictive accuracy. Key platforms are compared in terms of clinical usability. We present real-world use cases showing how ML-driven alerts can help optimize treatment plans and support patient education. Practical insights are provided on the evaluation, implementation, and limitations of these tools. ML is not a distant technology—it is already transforming pollen forecasting and allergy alerts. This article aims to equip allergologists with the knowledge needed to evaluate and adopt these tools, enabling a more proactive and personalized approach to managing pollen allergies.
DOI: https://doi.org/10.37349/eaa.2026.1009123
This article belongs to the special issue Climate Change, Allergy, and Immunotherapy
Major depressive disorder (MDD) is increasingly understood as a multifactorial psychiatric disorder involving interacting neural, immune, metabolic, and microbial processes. Within this framework, the microbiota–gut–brain axis and mitochondrial bioenergetics have emerged as potentially intersecting contributors to depressive symptomatology. Preclinical studies suggest that microbial metabolites—especially short-chain fatty acids (SCFAs)—can influence oxidative phosphorylation, redox balance, neuroinflammation, and synaptic plasticity, whereas inflammatory signals such as lipopolysaccharide may disrupt mitochondrial dynamics. However, the strength of evidence is uneven: mechanistic support is strongest in cell and animal models, whereas human data remain heterogeneous and largely associative. This narrative review critically synthesizes current evidence on microbiota–mitochondria crosstalk in MDD, distinguishing established findings from emerging hypotheses. It also examines recent psychobiotic trials, metabolomic and biomarker studies, and microglia–mitochondria mechanisms, and discusses the translational limitations that currently constrain clinical application. Overall, this axis represents a plausible and clinically relevant framework for hypothesis generation and adjunctive intervention development, but it should not yet be regarded as a fully validated causal pathway or stand-alone therapeutic target in MDD.
Major depressive disorder (MDD) is increasingly understood as a multifactorial psychiatric disorder involving interacting neural, immune, metabolic, and microbial processes. Within this framework, the microbiota–gut–brain axis and mitochondrial bioenergetics have emerged as potentially intersecting contributors to depressive symptomatology. Preclinical studies suggest that microbial metabolites—especially short-chain fatty acids (SCFAs)—can influence oxidative phosphorylation, redox balance, neuroinflammation, and synaptic plasticity, whereas inflammatory signals such as lipopolysaccharide may disrupt mitochondrial dynamics. However, the strength of evidence is uneven: mechanistic support is strongest in cell and animal models, whereas human data remain heterogeneous and largely associative. This narrative review critically synthesizes current evidence on microbiota–mitochondria crosstalk in MDD, distinguishing established findings from emerging hypotheses. It also examines recent psychobiotic trials, metabolomic and biomarker studies, and microglia–mitochondria mechanisms, and discusses the translational limitations that currently constrain clinical application. Overall, this axis represents a plausible and clinically relevant framework for hypothesis generation and adjunctive intervention development, but it should not yet be regarded as a fully validated causal pathway or stand-alone therapeutic target in MDD.
DOI: https://doi.org/10.37349/en.2026.1006133
This article belongs to the special issue Depression: From Pathophysiology to Treatment Innovation
Background:
Atrial fibrillation (AF) substantially increases the risk of ischemic stroke (IS), underscoring the need for effective anticoagulation strategies. Direct oral anticoagulants (DOACs) have largely supplanted vitamin K antagonists (VKAs) due to their favorable safety profile and ease of use. Factor XI (FXI) inhibitors, which target the intrinsic coagulation pathway, are emerging as potential alternatives that may offer reduced bleeding risk. This systematic review evaluates the efficacy and safety of FXI inhibitors compared with DOACs for stroke prevention in AF.
Methods:
A total of 20 studies fulfilled the inclusion criteria, comprising 11 randomized controlled trials (RCTs), five systematic reviews or meta-analyses, and four narrative, cohort, or modeling studies. Eligible investigations compared FXI inhibitors with DOACs in patients diagnosed with AF. The primary outcomes assessed were stroke or systemic embolism, major bleeding, and all-cause mortality. Methodological quality was evaluated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, the revised Cochrane Risk of Bias 2 (RoB 2) tool for RCTs, and the Newcastle-Ottawa Scale (NOS).
Results:
FXI inhibitors were associated with a significant reduction in major bleeding [relative risk (RR) 0.31; 95% confidence interval (CI) 0.21–0.46] and clinically relevant non-major bleeding (RR 0.66; 95% CI 0.47–0.93) compared with DOACs. Conversely, FXI inhibitors demonstrated an increased risk of stroke or systemic embolism (RR 3.17; 95% CI 2.18–4.62), as observed in the OCEANIC-AF trial [hazard ratio (HR) 3.79; 95% CI 2.46–5.83]. No significant difference was noted in all-cause mortality (RR 0.85; 95% CI 0.67–1.08). Limited evidence suggests that FXI inhibitors may also reduce bleeding-related hospitalizations.
Discussion:
FXI inhibitors provide a favorable bleeding profile but are less effective than DOACs for stroke prevention in patients with AF. Further long-term RCTs are warranted to delineate their role, particularly in populations at high risk of bleeding.
Background:
Atrial fibrillation (AF) substantially increases the risk of ischemic stroke (IS), underscoring the need for effective anticoagulation strategies. Direct oral anticoagulants (DOACs) have largely supplanted vitamin K antagonists (VKAs) due to their favorable safety profile and ease of use. Factor XI (FXI) inhibitors, which target the intrinsic coagulation pathway, are emerging as potential alternatives that may offer reduced bleeding risk. This systematic review evaluates the efficacy and safety of FXI inhibitors compared with DOACs for stroke prevention in AF.
Methods:
A total of 20 studies fulfilled the inclusion criteria, comprising 11 randomized controlled trials (RCTs), five systematic reviews or meta-analyses, and four narrative, cohort, or modeling studies. Eligible investigations compared FXI inhibitors with DOACs in patients diagnosed with AF. The primary outcomes assessed were stroke or systemic embolism, major bleeding, and all-cause mortality. Methodological quality was evaluated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, the revised Cochrane Risk of Bias 2 (RoB 2) tool for RCTs, and the Newcastle-Ottawa Scale (NOS).
Results:
FXI inhibitors were associated with a significant reduction in major bleeding [relative risk (RR) 0.31; 95% confidence interval (CI) 0.21–0.46] and clinically relevant non-major bleeding (RR 0.66; 95% CI 0.47–0.93) compared with DOACs. Conversely, FXI inhibitors demonstrated an increased risk of stroke or systemic embolism (RR 3.17; 95% CI 2.18–4.62), as observed in the OCEANIC-AF trial [hazard ratio (HR) 3.79; 95% CI 2.46–5.83]. No significant difference was noted in all-cause mortality (RR 0.85; 95% CI 0.67–1.08). Limited evidence suggests that FXI inhibitors may also reduce bleeding-related hospitalizations.
Discussion:
FXI inhibitors provide a favorable bleeding profile but are less effective than DOACs for stroke prevention in patients with AF. Further long-term RCTs are warranted to delineate their role, particularly in populations at high risk of bleeding.
DOI: https://doi.org/10.37349/ent.2026.1004148
This article belongs to the special issue Interdisciplinary Approach to Therapeutic Strategies of Neuroprotection in Present and Future
Recurrent infections in children often prompt evaluation for primary immunodeficiency diseases, particularly those affecting humoral immunity. Assessment of memory B cell subsets and vaccine-specific antibody responses provides critical insight into long-term protective immunity. While peripheral blood mononuclear cell (PBMC) isolation is common, direct whole blood staining offers faster processing, reduced cell loss, and better preservation of fragile B cell populations. This comprehensive protocol describes a standardised whole blood flow cytometry method for memory B cell phenotyping, alongside ELISA-based measurement of vaccine-specific antibody titres as part of assessing children with recurrent infections.
Recurrent infections in children often prompt evaluation for primary immunodeficiency diseases, particularly those affecting humoral immunity. Assessment of memory B cell subsets and vaccine-specific antibody responses provides critical insight into long-term protective immunity. While peripheral blood mononuclear cell (PBMC) isolation is common, direct whole blood staining offers faster processing, reduced cell loss, and better preservation of fragile B cell populations. This comprehensive protocol describes a standardised whole blood flow cytometry method for memory B cell phenotyping, alongside ELISA-based measurement of vaccine-specific antibody titres as part of assessing children with recurrent infections.
DOI: https://doi.org/10.37349/ei.2026.1003248
