Search Results (1,079)

Background: The introduction of targeted therapy in oncology has led to several challenges. These medicines are relatively new in clinical practice and are not well known to specialists with regard to adverse drug reactions (ADRs) and potential drug–drug interactions (pDDIs). In addition, cancer affects multiple body systems, including weight loss, anemia, liver and kidney function, depression, and pain. Patients frequently have comorbidities, leading to polypharmacy and the use of special foods, nutritional supplements, and herbal products for self-medication. Identification of pDDIs is essential, as concomitant use of multiple medicinal products increases the risk of ADRs and may compromise treatment. Objective: This study aims to retrospectively review and analyze data on ADRs and pDDIs in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) inhibitors and to evaluate the relationship between them. Method: EudraVigilance and UpToDate^® Lexidrug™ application were used to screen suspected ADRs and pDDIs, respectively. Descriptive statistical analysis was performed. Results: After reviewing Line Listing Reports (LLRs) from 2021 to 2023 in EudraVigilance, the number of suspected adverse drug reactions (ADRs) reported was higher when drug interactions classified as risk categories D and X were identified, compared with cases involving EGFR inhibitor monotherapy or other drug combinations. Of the 144 cases involving category D and/or X interactions, 63 demonstrated a possible association with the reported ADRs of EGFR inhibitors. The most common pDDIs detected were erlotinib–ranitidine (14 cases, category D) and osimertinib–amiodarone (13 cases, category D). Conclusions: Although EGFR inhibitors improve overall and progression-free survival in NSCLC, screening for pDDIs before treatment is essential to improve safety and quality of life. Full article

Chronic autoimmune thyroiditis (CAT), a common autoimmune thyroid disorder, is the leading cause of hypothyroidism in iodine-sufficient regions and is characterized by thyroid autoimmunity, chronic inflammation, and progressive structural thyroid changes. Although levothyroxine (LT4) restores biochemical euthyroidism, it does not directly address the underlying autoimmune process, highlighting the need for adjunctive therapeutic strategies. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), has been proposed as a non-invasive intervention with potential immunomodulatory and tissue-level effects. A systematic narrative review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting principles. PubMed/MEDLINE, Google Scholar, and additional databases were searched for original human clinical studies evaluating PBM/LLLT in CAT, including studies using the term Hashimoto’s thyroiditis (HT), and reporting thyroid-related outcomes. Due to heterogeneity in study designs and PBM protocols, findings were synthesized narratively. Six eligible clinical studies published between 2010 and 2025 were identified. Across studies, PBM was associated with reductions in thyroid autoantibodies, improvements in thyroid hormone indices, and decreases in LT4 dose requirements. Longer follow-up studies reported ultrasonographic changes, while one sham-controlled trial demonstrated improvements in oxidative stress markers and quality of life (QoL) without short-term endocrine changes. However, current evidence is limited by the small number of human studies, heterogeneous PBM protocols, and the frequent use of concomitant interventions such as selenium or vitamin D. Overall, PBM may represent a promising adjunctive approach in CAT, although randomized sham-controlled trials are required before clinical implementation. Full article

Background/Objectives: Endometrial cancer is one of the most common malignancies of the female reproductive system. Fortunately, risk-adapted therapy offers a promising chance of recovery, even from locally advanced disease. In particular, older patients with higher risk factors benefit markedly from adjuvant radiotherapy with or without chemotherapy. Nevertheless, this also carries a risk of higher cumulative toxicity thereafter. Although this phenomenon has been observed in older patients, it has not yet been adequately evaluated. Methods: This retrospective study compared the clinical features of patients receiving adjuvant radiotherapy with or without sequential chemotherapy or radiotherapy with concomitant chemotherapy between 2011 and 2023. The cohort was divided into two groups: patients over 65 years old and those under 65. Results: 100 patients received adjuvant radiotherapy at our center between 2011 and 2023. The mean age of patients was 66.87 years. We observed that neither diabetes, obesity, concurrent, sequential chemotherapy, nor para-aortic field irradiation was associated with an increased incidence of acute radiogenic side effects such as cystitis, diarrhea, proctitis, radiodermatitis, nausea, or vaginal dryness according to CTCAE ≥ 2 (all p > 0.50). No difference was found between the two groups in terms of the incidence of radiotherapy-associated toxicity. Conclusions: We found no increase in toxicity in elderly patients after adjuvant radiotherapy with or without chemotherapy. Full article

Background: Metabolic syndrome is a disorder characterised by the concomitant presence of obesity, hyperglycaemia, hypertension, hyperlipidaemia, and insulin resistance. An increasing body of research indicates that chronic inflammation, accompanied by oxidative stress and angiogenesis, plays a key role in the pathogenesis of the metabolic syndrome. Spice herbs may exert a beneficial effect when consumed daily in generally accepted amounts (1–3 g), thus providing relatively small quantities of bioactive compounds with anti-inflammatory properties. Their potential arises from regular long-term use rather than from the amount of bioactive substances delivered in a single dose. Methods: In this narrative review, we analysed data from the international literature on the effects of spice herbs (coriander, sage, mint, basil, rosemary, oregano and thyme) consumption on inflammation associated with metabolic syndrome in women. Results: The available literature provides limited data on the impact of spice herbs in the context of anti-inflammatory effects. A total of 124 publications were analysed, including 72 original research studies (48 involving humans) and 52 review articles and meta-analyses. Among the research articles included in the review, only 20 addressed both inflammation and at least one of the seven selected herbs: five were human studies, six involved laboratory animals, and eight were conducted in vitro. Analysis of the results from human studies demonstrated anti-inflammatory effects (decreases in TNF-α, IL-1β, IL-6, TLR4, hs-CRP) at daily doses not exceeding 3 g of individual herbs or 6.6 g of an herbal mixture. The use of spice herbs as a nutritional strategy to prevent chronic inflammation is supported by a growing body of scientific evidence. It should be emphasised that these studies are concerned with dietary support and prevention rather than with treatments that substitute for standard medical therapy. Incorporating spice herbs into the daily diet may represent a simple and safe approach to increasing the intake of anti-inflammatory bioactive compounds. Conclusions: Future research should focus on the precise determination of optimal doses and combinations of spice herbs to maximise benefits while avoiding potential adverse effects resulting from excessive intake of certain compounds or inappropriate selection of spice herbs. Long-term studies conducted in larger populations of women with metabolic syndrome are required, as physiological differences, particularly those related to oestrogens, may result in sex-specific effects. This review provides up-to-date information for further basic and clinical research on herbal medicine in metabolic syndrome. Full article

Background: Mitragynine pseudoindoxyl (MP) is a semi-synthetic kratom metabolite increasingly sold online and over-the-counter, marketed misleadingly as “kratom” or “7-OH,” despite lacking FDA approval and safety data in humans. Methods: This case report describes a 44-year-old male with polysubstance use history who developed opioid withdrawal symptoms after regular MP use (400 mg daily for pain management following neck injury). Vital signs, alcohol and opioid withdrawal scores and clinical outcomes were recorded. Results: The patient presented exhibiting symptoms of moderate opioid withdrawal in the absence of other opioid use. A buprenorphine macro-induction protocol was initiated. Following pre-treatment using chlorpromazine as an anti-emetic and diazepam to treat concomitant alcohol withdrawal, 32 mg buprenorphine were provided (16 mg × 2) on day one, with subsequent maintenance dosing and adjunctive medications. The patient demonstrated significant symptomatic improvement with decreased COWS scores and expressed interest in long-acting injectable buprenorphine maintenance therapy. Discussion: This represents the first documented case of suspected MP withdrawal successfully managed with buprenorphine macro-induction, demonstrating the potential efficacy of this approach for novel semi-synthetic kratom metabolites when standard withdrawal management protocols are insufficient. Further studies should evaluate long term outcomes and validate findings. Full article

Background: Chronic Obstructive Pulmonary Disease (COPD) is a common condition that can cause dyspnea, pain, and biomechanical-postural alterations, especially when overlapping with Myofascial Pain Syndrome (MPS). Balneological rehabilitation medicine can help manage COPD and MPS, but it lacks homogeneity and detailed descriptions of effective therapeutic protocols. Therefore, we conducted a case series to preliminarily evaluate the clinical effects of a detailed and codified approach, called Bio-Physico-Metric Integrated Thermal Care (BPM-ITC), for COPD+MPS. Methods: 10 patients were observed while undergoing 20 sessions of BPM-ITC in 4 weeks. Patients were assessed before and after the protocol using the Medical Research Council (MRC) dyspnea scale, Numeric Pain Rating Scale (NPRS), and the Bio-Postural Questionnaire (BPQ) for bio-physical health status. Treatments included manual therapy of key myofascial trigger points combined with crenotherapy, steam inhalations, mud therapy, vascular path, and water-based motor re-education. Results: At the end of the protocol, clinically relevant improvements were observed in almost all parameters considered in single observed cases; overall statistical analysis of the data highlighted significant positive effects in concomitance with the BPM-ITC protocol. Conclusions: The BPM-ITC protocol was followed by significant clinical improvements in the observed cases, suggesting its potential as a complementary approach for COPD+MPS. Further studies on this topic are recommended. Full article

Background: Furosemide is one of the most frequently prescribed loop diuretics for cardiovascular conditions, particularly in the management of volume overload and acute elevations in blood pressure. However, detailed real-world data describing its utilization characteristics and documented safety outcomes in primary healthcare settings remain limited, especially in underrepresented health systems. Objective: This study aimed to describe real-world patterns of furosemide utilization, including indications and concomitant treatment patterns, and to document associated adverse drug events and short-term clinical outcomes in routine primary healthcare practice. Methods: A retrospective pharmacoepidemiological observational study was conducted between January and December 2025 in a primary healthcare center. Medical records of 1300 adult patients who received furosemide for cardiovascular indications were reviewed. Indications included arterial hypertension, hypertensive crises, and conditions related to volume overload. Utilization characteristics were operationalized as indication distribution, monotherapy versus combination therapy, and recurrence patterns within the study period. Data collected included demographic characteristics, primary and comorbid diagnoses, blood pressure values recorded before and after administration, furosemide dose and route of administration, concomitant antihypertensive therapy, documented adverse drug events as recorded in routine clinical documentation, recurrent presentations related to hypertensive crises, and the need for hospital referral. Descriptive statistics and paired comparative analyses were performed, with statistical significance set at p < 0.05. Results: The mean patient age was 62.4 ± 11.8 years, with a male predominance (54.1%). Arterial hypertension was the most frequent recorded indication (78.6%), while 32.4% of patients had multiple cardiovascular diagnoses. A statistically significant reduction in systolic blood pressure (from 176.3 ± 18.5 mmHg to 148.7 ± 16.2 mmHg, p < 0.001) and diastolic blood pressure (from 101.2 ± 11.4 mmHg to 89.6 ± 9.8 mmHg, p < 0.001) was observed between measurements recorded before and after administration during the same clinical episode. Recurrent presentations related to hypertensive crises were documented in 27.9% of patients during the study period. Adverse drug events were documented in 9.6% of cases, most commonly dehydration and suspected electrolyte disturbances as noted in routine clinical records. Hospital referral was required in 6.8% of patients. Conclusions: In this real-world primary healthcare cohort, furosemide was commonly used across a heterogeneous mix of cardiovascular indications, predominantly in combination with other antihypertensive agents. Observed temporal reductions in blood pressure and documented adverse events reflect routine clinical practice rather than controlled treatment effects. These findings provide descriptive pharmacoepidemiological evidence from a primary care setting and underscore the importance of careful monitoring, documentation, and rational prescribing in patients receiving loop diuretics. Full article

Background: Orthostatic intolerance (OI) is an important factor affecting daily functional capacity in patients with long COVID. Traditionally, most OI symptoms have been attributed to exaggerated sympathetic nervous system activation associated with postural orthostatic tachycardia syndrome (POTS). Disequilibrium, also referred to as postural instability, may contribute to the development of OI in patients with long COVID. Methods: This study evaluated 32 patients with long COVID using neurological examinations and the active 10-min standing test. Disequilibrium was assessed using the Romberg and tandem gait tests. OI was defined as the inability to complete the active 10-min standing test. Results: Seven patients (22%) were diagnosed with OI. None of them had POTS, whereas six (86%) demonstrated disequilibrium, as detected by the Romberg and/or tandem gait test. POTS was observed in eight patients (25%), none of whom had OI. Disequilibrium was observed in nine patients (28%), six of whom (67%) had OI. Multiple regression analysis revealed that disequilibrium was positively associated with OI (r = 0.64, p < 0.001), whereas POTS was inversely associated (r = −0.38, p < 0.05). After 6 weeks of oral minocycline treatment in six patients and 2 weeks of repetitive transcranial magnetic stimulation therapy following minocycline in the other one patient, symptom amelioration was reported in six patients with OI. OI concomitant with disequilibrium recovered in five of the six patients treated and tested, although one patient who experienced symptom recovery failed to undergo the repeated standing test. Conclusions: Disequilibrium, rather than POTS, was the primary determinant of OI in patients with long COVID. Full article

Background/Objectives: The standard surgical treatment of muscle-invasive bladder cancer (MIBC) comprises neoadjuvant systemic therapy followed by radical cystectomy (RC). However, a notable number of patients achieve a favorable response to neoadjuvant systemic therapy, a finding associated with improved outcomes, and questioning the necessity of RC in this subset of patients. The objective of this review is to summarize the available evidence regarding the feasibility, efficacy and toxicity of bladder-preserving chemoradiotherapy (CRT) following clinical response (CR) to neoadjuvant systemic therapy in patients with MIBC. Methods: A literature search was performed using the PubMed database to identify studies evaluating the use of CRT for bladder preservation in MIBC patients with CR following neoadjuvant therapy. Results: Clinical complete response (cCR) rates to neoadjuvant systemic treatment ranged from 31% to 87.5%, with subsequent CRT enabling 50–97% of responders to retain their bladder. Long-term outcomes were favorable for cCR patients, with 3- to 5-year overall survival (OS) ranging from 65% to 89%, disease-free survival (DFS) of 64–86%, and bladder-intact survival up to 80%. Achievement of cCR, T2 tumor stage, absence of concomitant carcinoma in situ or hydronephrosis, and complete transurethral resection of the bladder tumor (TURBT) were prognostic factors for improved oncologic outcomes. Treatment-related toxicity was generally acceptable, concerning mainly hematological and gastrointestinal events, while severe late toxicity was uncommon. Conclusions: Bladder-preserving CRT is a promising, effective, and well-tolerated option for MIBC patients achieving CR to neoadjuvant systemic therapy. While further prospective validation and longer follow-up are required before it can universally replace radical cystectomy in this subset of patients, advances in neoadjuvant treatments, imaging and molecular biomarkers may improve response assessment and patient selection for bladder preservation. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease effectively treated with dupilumab, a monoclonal antibody that inhibits IL-4 and IL-13 signaling. Dupilumab is an effective treatment for type 2 inflammatory diseases such as CRSwNP. Although efficacy of dupilumab in controlling upper airway inflammation is well established, concerns have emerged regarding its potential cardiovascular effects. Emerging evidence suggests that IL-4/IL-13 signaling plays a protective role in post-myocardial infarction remodeling by promoting anti-inflammatory macrophage polarization, angiogenesis, and controlled fibrosis, especially during the early healing phase. Pharmacological blockade of the IL-4/IL-13 signaling pathway, such as that induced by dupilumab, may theoretically impair myocardial repair mechanisms, particularly in male patients who appear more responsive to these cytokines. Although rare, dupilumab-associated hypereosinophilia and myocarditis have been reported. In patients with pre-existing ischemic heart disease or heart failure, a multidisciplinary risk–benefit evaluation should be considered. Concomitant use of cardioprotective agents such as sacubitril/valsartan or SGLT2 inhibitors may help mitigate potential cardiac risks. Future studies are needed to clarify the safety and therapeutic implications of combining dupilumab with cardiovascular therapies in patients with coexisting CRSwNP and heart disease. This review critically evaluates emerging evidence of potential interference with post-infarction myocardial repair and highlights the importance of a multidisciplinary approach in managing patients with coexisting inflammatory and cardiovascular diseases. The aim of this review is to explore the available data on the cardiovascular impact of dupilumab and to provide possible future perspectives. Full article

Introduction: Stereotactic radiotherapy (SRT) is increasingly used in oligometastatic non-small-cell lung cancer (NSCLC) and is known to elicit systemic immune effects, although the underlying mechanisms remain not fully understood. Methods: In this prospective pilot study, we evaluated plasma cytokine variations in 19 patients with oligometastatic or oligoprogressive NSCLC undergoing SRT. Peripheral blood samples were collected before treatment (T0) and one month after SRT (T1) and the concentrations of nine cytokines (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A and TNF-α) were quantified using a multiplex Luminex assay. Non-parametric tests and Cox regression models were used to investigate associations between cytokine levels, clinical variables, systemic treatments, and survival outcomes. SRT induced significant post-treatment increases in IFN-γ, IL-2, and IL-6, consistent with systemic pro-inflammatory activation and T-cell stimulation. Cytokine dynamics were influenced by patient- and tumor-related factors: female sex was associated with higher IL-2 and TNF-α levels; oncogene-addicted tumors showed lower IL-6 levels; and oligoprogressive disease exhibited attenuated cytokine variations compared with metachronous oligometastatic disease. Tyrosine kinase inhibitors were associated with globally reduced cytokine levels and blunted IL-1/IL-2 changes, whereas patients receiving immune checkpoint inhibitors displayed higher IL-2 and IL-6 concentrations and greater post-SRT increases in IFN-γ. Oncogene-addicted status and IL-12 variation emerged as independent predictors of overall survival and a composite model integrating these variables significantly stratified prognosis. Conclusions: These findings suggest that SRT triggers measurable systemic immune activation in oligometastatic NSCLC, which is further shaped by tumor biology, disease burden, and concomitant systemic therapies. Although limited by the small sample size, this study supports the feasibility and potential utility of cytokine profiling to refine patient selection and guide biomarker-driven combinations of SRT with targeted and immune-based treatments, warranting validation in larger prospective cohorts. Full article

Pharmacotherapy is a key component of obesity management, yet treatment failure remains a prevalent challenge in clinical practice. Such failure may present as insufficient pharmacological response, early discontinuation, or post-treatment weight regain, underscoring the discrepancy between clinical trial efficacy and real-world outcomes. The effectiveness of anti-obesity medications (AOMs) is influenced by psychiatric comorbidities, including depression, anxiety, and disordered eating patterns, as well as environmental and socioeconomic factors such as limited healthcare access, weight-related stigma, and high medication costs. Individual characteristics, including physical activity, body composition, visceral adiposity, and microbiome profile, further modulate treatment outcomes. Pharmacokinetic and pharmacotherapeutic limitations such as drug-phenotype mismatch, route of administration, suboptimal formulations, and exposure to counterfeit products also compromise efficacy. No less important are genetic and immunological factors, comprising pharmacogenomic variants of both incretin and melanocortin receptors along with antidrug antibodies (ADAs), which may constitute therapy resistance. Concomitant medications and comorbid endocrine disorders can additionally attenuate weight-loss effects. The objective of this review is to characterize the multifactorial nature of resistance and refractoriness to anti-obesity therapy, and the importance of identifying pretreatment predictive factors for recognizing individuals at risk of inadequate or lack of response, thereby enabling personalized management strategies and improving long-term clinical outcomes, particularly in “difficult-to-treat” patients. Full article

Background/Objectives: Familial Mediterranean fever (FMF) is the most common periodic fever syndrome worldwide, and persistent subclinical inflammation has been reported in 10–20% of cases during attack-free periods. Although the immunomodulatory effects of vitamin D, vitamin B12 and folate have been investigated in various conditions, data on their relationship with subclinical inflammation in FMF patients remain limited. This study aimed to evaluate the association between micronutrient levels and subclinical inflammation in pediatric FMF. Methods: Children aged 2–18 years with an FMF diagnosis of more than two years, receiving regular colchicine therapy, and attack-free for at least two months were included. Patients with other autoinflammatory diseases, colchicine resistance, concomitant renal disease, active infection, or inadequate follow-up were excluded. Demographic, clinical, genetic, and biochemical data were analyzed. Results: A total of 253 patients were included, with a median age of 14 years (range, 3–18), and 133 (52.6%) were female. Persistent subclinical inflammation was observed in 31 patients (12.3%). Genetic analysis revealed homozygous M694V mutations in 71 patients (28%). Median vitamin levels were as follows: vitamin D 17.3 ng/mL (IQR 10.6–27.1), vitamin B12 288 pg/mL (IQR 214–367), and folate 6.4 ng/mL (IQR 4.8–7.6). Comparison between patients with and without subclinical inflammation showed no significant differences in micronutrient levels. Conclusions: Although micronutrients have been reported to play immunomodulatory roles, we did not observe significant association between vitamin levels and subclinical inflammation in pediatric FMF patients in our study. Full article

Background: Acquired hemophilia A (AHA) is a bleeding disorder caused by autoantibodies against coagulation factor VIII. Treatment includes controlling bleeding and eliminating the inhibitor. Emicizumab has been increasingly used to prevent bleeding in patients with AHA. Rituximab is used as a first-line immunosuppressive therapy (IST) for AHA, either in combination with corticosteroids in high-risk patients or as monotherapy in low-risk patients who cannot tolerate corticosteroids. However, evidence regarding concomitant emicizumab and rituximab as first-line treatment for AHA is limited. Case presentations: We present five cases of AHA diagnosed at a single institution. The first three high-risk AHA cases in the era before emicizumab resulted in poor outcomes due to bleeding (Cases 1 and 3) or infection (Case 2). The recent cases (Cases 4 and 5) were successfully treated with emicizumab and rituximab-containing IST without severe bleeding and infections. Since emicizumab effectively relieved pain in these patients, rehabilitation could be initiated promptly, resulting in earlier hospital discharge. Complete remission was achieved on Day 42 in Case 4 and on Day 22 in Case 5, respectively, and emicizumab was subsequently discontinued in both cases. Conclusions: Our case series suggests that early initiation of emicizumab for patients with AHA is effective in preventing severe bleeding and subsequent immobility, and it can be combined with rituximab-containing IST to achieve remission, potentially with fewer adverse effects than standard IST. Further studies are warranted to establish the optimal treatment protocol involving emicizumab and IST for AHA. Full article

Background/Objectives: Type 2 diabetes (T2DM) and hypothyroidism often coexist, worsening cardiometabolic risk. Oral semaglutide and levothyroxine each improve metabolic parameters, but the effect of combined therapy is understudied. This study aimed to evaluate whether oral semaglutide administered concomitant with levothyroxine provides additive benefits on lipid profile, glycemic control, and body weight in patients with both conditions. Methods: This prospective comparative observational study assessed a total of 210 patients who were enrolled (70 per group) with a 6-month follow-up. Group A (T2DM and hypothyroidism) received semaglutide and levothyroxine, group B (hypothyroidism only) received levothyroxine, and group C (T2DM only) received oral semaglutide. Lipid profile, glycemic profile (HbA1c), thyroid profile, and anthropometric parameters were comparable across groups at baseline and after 6 months. Results: Group A demonstrated significant improvements in lipid parameters: LDL-cholesterol decreased by 12.7%, HDL increased by 9.0%, and triglycerides decreased by 6.7% (all comparisons p < 0.001 unless otherwise specified). In contrast, group B experienced worsening lipid profiles (LDL increased by 11.0%, HDL decreased by 0.5%, and triglycerides increased by 9.1%), while group C showed modest changes (LDL increased by 4.5%). Glycemic control improved among diabetic patients, with HbA1c declining by 7.7% in group A and 12.6% in group C. Body mass index (BMI) decreased in groups A (4.9%) and C (6.0%). Conclusions: The concurrent administration of oral semaglutide and levothyroxine produces additive cardiometabolic advantages in individuals with T2DM and hypothyroidism. These findings suggest that combined treatment may optimize metabolic outcomes in this particularly high-risk population. Full article