Search Results (1,288)

Background: Menstrual migraine (MM), including pure menstrual migraine (PMM) and menstrually related migraine (MRM), is characterized by attacks occurring in close temporal association with menstruation and is often more severe, longer lasting, and less responsive to treatment than non-menstrual migraine. Prostaglandin-mediated inflammation and calcitonin gene-related peptide (CGRP) release play a key role in MM pathophysiology. Phycocyanin (PC) and palmitoylethanolamide (PEA) are nutraceutical compounds with anti-inflammatory, analgesic, and neuroprotective properties that may be beneficial as short-term perimenstrual prophylaxis. Objectives: To evaluate the effectiveness of an oral supplementation combining phycocyanin and palmitoylethanolamide as a short-term prophylaxis for menstrual migraine in a real-world clinical setting, a retrospective observational study without a control group was conducted in five Italian centers between May 2023 and June 2025. Methods: Clinical records of 800 women were reviewed, and 220 patients receiving perimenstrual supplementation with phycocyanin and palmitoylethanolamide were screened. Sixty-one women diagnosed with migraine without aura, according to the International Classification of Headache Disorders, met all inclusion criteria and were analyzed. Phycocyanin and palmitoylethanolamide were taken at a dosage of two capsules daily from five days before to five days after the onset of menstruation for three consecutive months. Outcomes during the perimenstrual window were compared with a three-month period without supplementation. Primary outcomes included migraine severity, frequency, and duration of the attacks; secondary outcomes included analgesic consumption and menstrual migraine-associated symptoms. Results: Among the 61 included patients, phycocyanin and palmitoylethanolamide supplementation was associated with a significant reduction in migraine severity across all monitored perimenstrual days (p < 0.0001). While the overall monthly frequency of migraine attacks did not change, the number of migraine days during the perimenstrual window significantly decreased from the first month of supplementation (p < 0.05). Moreover, migraine duration during the perimenstrual window was significantly reduced at one, two, and three months of phycocyanin and palmitoylethanolamide supplementation compared with baseline. Analgesic use and the number of days with migraine-associated symptoms (nausea, vomiting, photophobia/phonophobia) were also significantly reduced. Treatment was well tolerated. Conclusions: In this real-world retrospective study, perimenstrual supplementation with phycocyanin and palmitoylethanolamide was associated with reduced severity, duration, and perimenstrual frequency of menstrual migraine attacks, along with decreased analgesic use, suggesting a safe and potentially beneficial short-term prophylactic strategy for women with menstrual migraine. Full article

Background: Persistent cervical human papillomavirus (Human papillomavirus) infection remains a significant public health concern, as it is the primary etiological factor in the development of cervical cancer and its precursor lesions. While prophylactic vaccination and standard screening programs are cornerstones of prevention, a substantial proportion of women with established infection are managed conservatively, often with prolonged follow-up and associated psychological burden. Interest has therefore grown in supportive interventions that may facilitate viral clearance during routine clinical management. Methods: This retrospective cohort study included 239 women with confirmed cervical Human papillomavirus infection followed at a tertiary referral center between February 2023 and August 2025. Participants were classified into a treatment group receiving oral Papivir/Pavirona^® twice daily for six months (n = 119) and a control group managed with routine clinical follow-up alone (n = 120). Human papillomavirus DNA testing and cervical cytology were evaluated at baseline and at 6 and 12 months. Results: Human papillomavirus clearance rates were significantly higher in the Papivir/Pavirona^® group compared with controls at both 6 and 12 months. Cytological regression was also more frequent in the treatment group at both time points. In multivariate logistic regression analysis, Papivir/Pavirona^® use emerged as the only independent predictor of both Human papillomavirus clearance and cytological regression, while demographic, reproductive, behavioral, and virological baseline characteristics were not significantly associated with outcomes. Conclusions: Papivir/Pavirona^® supplementation was associated with increased Human papillomavirus clearance and cytological regression rates in women with cervical Human papillomavirus infection, suggesting a potential supportive role alongside standard clinical follow-up. Full article

Background and Objectives: Hereditary angioedema (HAE) represents a specific form of life-threatening inborn errors of immunity. Current guidelines recommend regular assessment of the disease burden, disease control and quality of life. This study describes the profile of HAE patients in Slovakia, disease control, quality of life, states of anxiety and depression, and socioeconomic situation. Materials and Methods: We used a set of standardized questionnaires—AE-QoL, AECT, HADS and Socioeconomic Status Questionnaire, and a non-standardized questionnaire—to describe the characteristics of the population. Results: We collected data on 56.44% (57 out of 101) of HAE adult patients registered in Slovakia. Moderate to severe HAE was present in 61.40% of patients; 73.68% were on long-term prophylactic treatment; and 19.30% received rescue treatment due to an acute HAE attack during the last 4 weeks. Most patients achieved lower AE-QoL scores, indicating a good quality of life. The AECT score indicated well-controlled disease in 91.23% of patients. Anxiety and/or depression scores were higher than normal in 17.54% of patients. Patients with HAE earned less than the average population, but most of them were economically active with relatively low rates of presenteeism and absenteeism. Only a minority of patients used social system benefits. Patients were exclusively cared for by relatives. Conclusions: The QoL scores achieved in all three standardized questionnaires indicate a good quality of life of HAE patients in Slovakia, which is associated with a high and specialized standard of care. Anxiety and/or depression were present in 17.54% of patients. Direct patients costs and social care costs are low, but there is an indirect socioeconomic burden on patients and their families. Full article

Background: Mirvetuximab soravtansine (MIRV) improves outcomes in FRα-positive, platinum-resistant ovarian cancer; however ocular adverse events (OAEs), particularly corneal epithelial toxicity, are frequent and warrant structured ophthalmologic monitoring. Methods: In this retrospective observational study, 31 consecutive patients receiving MIRV for FRα-positive gynecologic malignancies underwent standardized ophthalmic assessments at baseline and prior to each treatment cycle (every 21 days). The protocol included best corrected visual acuity (BCVA), slit-lamp biomicroscopy, anterior-segment optical coherence tomography (AS-OCT), corneal topography, and tear film analysis. OAEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, based on symptom severity and functional impairment. Results: OAEs occurred in all patients (31/31, 100%), predominantly grade 1–2. Corneal epithelial toxicity was documented in 28/31 patients (90.3%), while no grade ≥ 3 events were observed. Symptoms typically developed 7–14 days after the second infusion. AS-OCT and corneal topography consistently revealed epithelial microcysts and surface irregularities, which were usually detected during scheduled pre-cycle ophthalmologic evaluations. Tear-film instability (break-up time ≤ 5 s) developed in 19/31 patients (61.3%), generally within 10 days after the second infusion, and improved in all but 2 patients (6.5%) following prophylactic lubrication. Transient refractive changes occurred in 28/31 patients (90.3%) and were associated with a temporary BCVA reduction (mean nadir ~20/32 Snellen), followed by recovery during follow-up. Conclusions: MIRV-related ocular alterations are frequent but reversible and clinically manageable. Multimodal imaging combined with functional and refractive assessment provides sensitive markers of corneal epithelial toxicity and supports integrated ophthalmologic monitoring to preserve visual function and maintain oncologic treatment continuity. Full article

Drug-induced nephrotoxicity is a leading cause of acute kidney injury (AKI) and subsequent chronic kidney disease. Nephrotoxicity often develops as a consequence of treatment with commonly prescribed aminoglycoside antibiotics, and remains a significant clinical challenge. One approach to treating AKI and its associated complications is caloric restriction or its pharmacological mimetics. This study aimed to evaluate the effects of caloric restriction mimetic hydroxycitrate (HC) in gentamicin-induced nephrotoxicity, with particular focus on the influence of treatment duration and the underlying molecular mechanisms. In vitro renal tubular epithelial cells models were used to assess HC’s effects on viability, proliferation, and autophagy activation. For in vivo validation, rats with gentamicin-induced AKI received HC treatment via two distinct regimens (3-week and 7-week administration). Experiments on renal tubule cells showed that HC significantly increased cell viability and proliferation and led to the activation of autophagy. In the rat model, only the 7-week administration of HC demonstrated significantly attenuated renal dysfunction in gentamicin-induced AKI. Moreover, it reduced macrophage infiltration, increased renal cell tolerance to apoptosis, activated autophagy, and reduced oxidative stress. Thus, our results indicate that 7-week HC administration could be used as a prophylactic strategy against antibiotic nephrotoxicity, exerting its effects by promoting autophagy, resisting apoptosis, and attenuating oxidative damage. Full article

Background: Sleep disturbance is a well-recognized contributor to headache burden, yet the specific sleep domains associated with disability may differ between episodic migraine (EM) and episodic cluster headache (ECH). Methods: In this prospective observational study, 20 EM patients, 21 ECH patients, and 18 age-, sex-, and BMI-matched healthy controls (HCs) were evaluated during interictal periods. None of the patients were receiving prophylactic headache treatment. Sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and Sleep Hygiene Index (SHI). Psychological status was measured with the Hospital Anxiety and Depression Scale (HADS). Headache-related disability was assessed using the Headache Impact Test-6 (HIT-6) as a continuous outcome. Separate multivariable linear regression models were constructed for each headache group. Results: Both headache groups showed significantly impaired sleep and higher anxiety and depression scores compared with controls (all p < 0.001). HIT-6 scores did not differ between EM and ECH (p = 0.770 after Bonferroni correction). In multivariable regression, excessive daytime sleepiness (ESS) independently predicted disability in EM (B = 1.633, p = 0.033; R² = 0.571). In ECH, global sleep quality (PSQI; B = 0.701, p = 0.004) and sleep hygiene (SHI; B = 0.557, p = 0.033) were independently associated with HIT-6 (R² = 0.562). No significant multicollinearity was observed (all VIF < 2.5). Conclusions: Sleep disturbance is prevalent in both EM and ECH; however, the sleep domains associated with disability differ between phenotypes. Daytime sleepiness is more relevant in EM, whereas global sleep quality and sleep hygiene are more strongly associated with disability in ECH. These findings support a phenotype-specific approach to sleep assessment in headache management. Full article

Background: An appropriate and effective management of haemophilia is currently based on a multidimensional evaluation of treatment adequacy. Current clinical practice however is still lacking standardised tools able to combine clinical, functional, and patient-reported outcomes. In this study a structured Monitoring Tool for haemophilia A and B was developed and validated through a Delphi-based expert consensus process. This study represents an expert consensus-based validation of a monitoring framework, rather than a clinical validation in patient cohorts. The tool is intended for use by haemophilia treaters during routine follow-up visits to support structured treatment reassessment. Score categories reflect the need for clinical re-evaluation or potential treatment optimisation, rather than disease severity. Methods: Italian haemophilia specialists were asked to participate to a panel over a two-round Delphi process. Experts rated the relevance of several predefined clinical domains—pharmacokinetics, bleeding episodes, joint health, adherence and quality of life (QoL)—and the individual items within each domain for patients on prophylactic or on-demand treatment. Consensus was defined by responses within an interquartile range (IQR) < 8. Section and item weights and Likert-based scoring values were used to reach a composite score between 0 and 100. Results: Consensus was achieved for all domains and items across haemophilia types and treatments, prophylaxis and on demand (Haemophilia A: 16 and 12 participants; Haemophilia B: 12 and 9, respectively). With reference to prophylaxis domains, bleeding episodes received the highest domain weight (31–32%), followed by joint health (27–29%) and adherence/QoL (21–23%) and pharmacokinetics (18–19%). For on-demand treatment, pharmacokinetics was excluded; bleeding episodes (38–40%) and joint health (35–37%) remained dominant. At the item level, dynamic joint health indicators (HJHS and HEAD-US changes) and longitudinal QoL changes consistently received the highest weights. The final scoring system categorised results as Excellent (0–25), Suboptimal (26–50), Poor (51–75), or Critical (76–100). Conclusions: The Delphi-validated Monitoring Tools provide a structured, weighted, and clinically relevant framework for assessing treatment adequacy in haemophilia A and B across prophylactic and on-demand settings. These tools allow multidimensional outcome assessment and may support a more consistent, personalised therapeutic decision-making. A prospective validation of the tool in clinical cohorts is warranted. Full article

Background and Objectives: The benefits of prophylactic supraclavicular lymph node dissection for esophageal squamous cell carcinoma (ESCC) remain controversial. This study investigated whether prophylactic supraclavicular (cervical) lymphadenectomy improves the long-term outcomes of patients with upper or middle thoracic esophageal squamous cell carcinoma. Materials and Methods: This retrospective, single-center study included 290 patients who underwent thoracoscopic esophagectomy between January 2010 and December 2017. Patients treated with two-field lymphadenectomy (2FL) were compared with those who underwent prophylactic three-field lymphadenectomy (p3FL) after propensity score matching based on age, tumor location, clinical T and N stage, and preoperative treatment. The primary outcome was overall survival (OS), and secondary outcomes included postoperative complications and recurrence patterns. In a secondary analysis, the long-term outcomes were assessed in patients with solitary postoperative cervical (supraclavicular) lymph node recurrence in the 2FL group. Results: In the overall cohort, statistically significant differences were observed between the groups with respect to age, tumor location (p = 0.0002), cT and cN stages (p < 0.0001 and p < 0.0001), preoperative treatment (p = 0.02). No significant differences were observed between groups regarding age, organ for reconstruction, or postoperative complications. After propensity score matching, no significant differences were observed between the 2FL and p3FL groups in terms of overall survival or postoperative complications. Six patients (4.4%) in the p3FL group had pathologically confirmed supraclavicular lymph node metastasis, whereas four patients (2.6%) in the 2FL group developed solitary postoperative cervical lymph node recurrence. Patients with isolated cervical recurrence achieved favorable long-term survival following additional treatment. Conclusions: Prophylactic cervical lymphadenectomy did not improve the survival of patients with upper or middle thoracic esophageal squamous cell carcinoma. Given the low incidence of isolated cervical lymph node recurrence and the favorable outcomes achievable with additional treatment, routine prophylactic supraclavicular dissection appears unnecessary when two-field lymphadenectomy is feasible. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus are dangerous respiratory pathogens with high pandemic potential. Since 2021, these two viruses have been co-circulating, which implies additional risks of co-infection with both pathogens. Prophylactic vaccination is widely recognized as the most effective way to prevent COVID-19 and influenza and to reduce the severity of these diseases. This review analyzes recent data on the simultaneous circulation of influenza and SARS-CoV-2 viruses worldwide, including epidemiological data and the pathogenetic mechanisms of co-infection. Next, we focus on current approaches to simultaneous and combined vaccination against influenza and COVID-19. We outline the types of vaccines and summarize the available findings on the effectiveness and safety of co-vaccination. Methods: A comprehensive search was conducted using PubMed, Scopus, Web of Science, and ClinicalTrials to identify data relevant to SARS-CoV-2 and influenza co-circulation and dual vaccination. Results: Influenza and SARS-CoV-2 cause similar symptoms, and co-infection can significantly enhance the risks of pneumonia and acute respiratory distress syndrome progressing with a poor outcome, especially among children and the elderly. A range of influenza and COVID-19 vaccines built on different technological platforms is currently available on the market, with proven effectiveness, immunogenicity, and safety. A co-vaccination approach is more convenient for patients and is associated with better response to treatment, while also improving vaccine coverage and compliance and offering significant resource savings for healthcare systems. Conclusions: The concurrent circulation of SARS-CoV-2 and influenza viruses presents a growing public health challenge. Simultaneous and combination vaccination strategies have emerged as effective tools to streamline immunization, enhance protection, and reduce healthcare burden. Future studies should elucidate the mechanisms of the exacerbation of respiratory disease caused by co-infection, as well as the optimal strategies for co-administering influenza and COVID-19 vaccines for long-term control of seasonal and potentially pandemic respiratory viruses. Full article

The development of antimicrobial resistance (AMR) and the emergence of multiresistant pathogens represent a growing global threat to both human and animal health. Beyond the excessive and improper use of antimicrobials in human medicine, irrational use in veterinary medicine, agriculture, and aquaculture significantly contributes to the selection and spread of resistant microorganisms, which can enter the food chain and reach humans through food consumption or handling. Based on results from a recent meta-analysis, the prevalence of antimicrobial-resistant foodborne pathogens in food samples exceeds 10%. The veterinary sector is of particular concern, as a large proportion of antimicrobials are used in animal production, generating strong selective pressure and favoring the dissemination of AMR along the food chain. In an increasingly interconnected global context, resistant pathogens and resistance determinants can disseminate rapidly across sectors and national borders, making strategies confined to a single sector insufficient; therefore, effectively addressing AMR requires a One Health approach encompassing the human, veterinary, and environmental domains. Key mitigation strategies include strengthening antimicrobial stewardship programs, also in animal production, reducing routine prophylactic use of antimicrobials, and improving surveillance, coordinated across sectors and, where possible, further supported by advanced technologies such as artificial intelligence and machine learning. Further efforts are also needed to improve microbiological diagnostics, particularly through rapid and molecular methods, to support timely, targeted therapies and reduce inappropriate empirical treatments. In parallel, investment in new therapeutic options, including innovative molecules, drug combinations, and alternative approaches, remains crucial to effectively countering the growing burden of antimicrobial resistance. Full article

Objective: To investigate how the high-altitude environment modifies severe pertussis in young infants and analyze its pathophysiological mechanisms and clinical management implications. Methods: Clinical data of two young infants with severe pertussis residing at 3650 m were retrospectively analyzed, including presentation, laboratory findings, pathogen detection, treatment, and outcomes. A literature review explored synergistic interactions between high-altitude factors and pertussis pathophysiology. Results: Case 1 had macrolide-resistant Bordetella pertussis (MRBP, 23S rRNA A2047G) with peak WBC 52.25 × 10⁹/L, and received cefoperazone-sulbactam, piperacillin-tazobactam and azithromycin, and was successfully treated with trimethoprim-sulfamethoxazole combined with exchange transfusion. Case 2 had Bordetella pertussis confirmed by PCR with peak WBC 36.55 × 10⁹/L, receiving cefoperazone-sulbactam and azithromycin, and recovered. Both developed respiratory failure requiring non-invasive ventilation and survived without pulmonary hypertension. High-altitude stressors—hypoxia, enhanced pulmonary vascular reactivity, and hypercoagulability—synergize with pertussis-induced hyperleukocytosis as a “dual hit,” accelerating cardiopulmonary deterioration and elevating thrombotic risks. Conclusions: High altitude is an independent risk modifier in infantile pertussis, demanding heightened vigilance and proactive interventions: early non-invasive ventilation, prophylactic anticoagulation, and timely exchange transfusion before pulmonary hypertension develops. This is the first high-altitude case series that provides essential insights for clinicians in similar environments globally, guiding early recognition and proactive management strategies to improve outcomes in this vulnerable population. Full article

Venothromboembolic (VTE) events are considered rare complications following foot and ankle surgery. Most instances of VTE following surgical procedures occur in particularly high-risk patient populations; therefore, VTE prophylactic anticoagulation is initiated based on risk/benefit stratification for each individual patient undergoing foot and ankle surgery. We present a case report on a 40-year-old male who underwent isolated Lisfranc ligament repair and subsequently developed an acute saddle pulmonary embolism and deep vein thrombosis 1 month postoperatively. The patient was on prophylactic Lovenox, yet still developed a life-threatening complication. The patient was found to be on a selective estrogen receptor modulator for the off-label treatment of male infertility. This medication, surgical intervention, and a period of non-weight bearing are believed to be contributory to the patient’s relatively increased hypercoagulable state. This case depicts a rare complication of foot and ankle surgery and highlights the importance of VTE prophylaxis during the postoperative period. Full article

Background/Objectives: Prophylactic mastectomy can significantly reduce the risk of breast cancer in patients carrying gene mutations such as BRCA1 and BRCA2. Patients who opt for breast removal are offered tailored reconstructive options based on their medical history and prior treatments, and in these often young patients with limited autologous tissue reserves, implant-based reconstruction is frequently the option of choice. Complication rates of these procedures are relatively high and account for up to 30%. Subcutaneous mastectomy with primary implant reconstruction carries risks such as hematoma, seroma, skin necrosis, necrosis of the nipple–areola complex, and wound healing issues, which may necessitate revision surgery. This university-center retrospective analysis aims to improve outcomes by identifying patient- and surgery-related risk factors associated with postoperative complications in allogenic breast reconstruction following subcutaneous mastectomy. Methods: We analyzed 61 female patients and 122 breasts who underwent primary implant-based reconstruction after skin- or nipple-sparing subcutaneous mastectomy over three years between January 2021 and December 2023. Demographic and surgical variables were systematically collected and analyzed. Results: The mean patient age was 41.5 ± 10.3 years. A total of 13% of patients were active smokers, and 1.6% had diabetes mellitus. Overall, skin flap necrosis occurred in 27.9% of patients (22.1% of breasts), wound healing disorders in 19.7% of patients, wound infections in 9.8%, and revision surgery in 18.0%. A history of pregnancy was associated with skin flap necrosis (OR 10.07, 95% CI 1.79–190.06; p = 0.032); however, this finding must be interpreted with caution due to limited statistical power and model instability. Conclusions: This investigation revealed clinically relevant patterns suggesting potential risk factors for wound healing disorders and skin necrosis. Prospective studies are planned to further substantiate these findings and to help reduce overall complication rates associated with the procedure. Full article

Porcine epidemic diarrhea virus (PEDV), a coronavirus responsible for severe watery diarrhea in neonatal piglets, leads to significant economic losses globally. Effective prevention and treatment of PEDV infection is critical to the swine industry. Currently, there are no available therapeutic drugs for PEDV. Porcine interferons (poIFNs) have been identified as promising molecules against a series of swine viruses due to their broad-spectrum antiviral and immunomodulatory properties. In this study, we demonstrated that type I interferon-α (IFN-α) offered both prophylactic and therapeutic benefits against PEDV infection. Recombinant poIFN-α produced by a prokaryotic expression system was purified through affinity chromatography, and its prophylactic and therapeutic effects against PEDV infection were evaluated in vitro and in vivo through RT-qPCR, clinical symptom monitoring, and pathological examination. In vitro studies revealed a strong antiviral activity of poIFN-α against PEDV in Vero E6 cells, with a more pronounced prophylactic effect compared to therapeutic outcomes. In vivo studies showed that poIFN-α significantly alleviated clinical diarrhea in PEDV-infected piglets and reduced intestinal viral loads. These findings suggest that poIFN-α holds considerable promise as an antiviral agent for PEDV and provides a foundation for the development of therapeutic strategies targeting this virus. Full article

Background/Objectives: Messenger RNA (mRNA) vaccine technology has shown great potential in the prevention of infectious diseases and treatment of cancers, but its full potential is limited by non-specific delivery mediated by the current lipid nanoparticle (LNP) platform. Methods: Here, we developed a dendritic cell (DC)-targeting LNP incorporated with an ultra-high-affinity CLEC9A-specific nanobody that facilitates enhanced DC uptake but reduced liver accumulation. We assessed the therapeutic efficacy of nanobody-functionalized lipid nanoparticles (Nb-LNPs) in a mouse Lewis lung carcinoma (LLC) model, alongside an evaluation of T cell-mediated immune responses and dendritic cell activation, facilitated by the delivery of mRNA-based neoantigen vaccines. Results: Compared with the use of an unfunctionalized LNP, personalized mRNA cancer vaccines encapsulated with this Nb-LNP demonstrated not only superior anti-tumor effects but also a favorable bio-safety profile in a mouse Lewis lung carcinoma model. The mRNA Nb-LNP neoantigen vaccines also induced substantially higher levels of DC maturation and more potent antigen-specific T cell responses, in particular CD4⁺ T cell responses, which are critical for initiation of anti-tumor immunity and immune memory. Conclusions: Taken together, these results suggest that precision-engineered LNPs conjugated with a CLEC9A-specific antibody or nanobody could be a promising platform for delivering mRNA vaccines specifically to dendritic cells, improving their prophylactic or therapeutic effects. Full article