Search Results (383)

Background/Objectives: Understanding the relationship between reactogenicity and immunogenicity after repeated BNT162b2 vaccination is critical for optimizing vaccination strategies. This study quantified their progressive dissociation across four vaccine doses. Methods: We conducted a prospective longitudinal cohort study among Croatian healthcare workers vaccinated with BNT162b2 from January 2021 to January 2024. Anti-SARS-CoV-2 IgG antibodies were measured at 16 timepoints using chemiluminescent immunoassay. Local (pain, erythema, swelling) and systemic (fever, fatigue, headache, myalgia, arthralgia, nausea) reactions were recorded for 7 days using FDA toxicity scale. Correlations were analyzed with Spearman’s method and Bonferroni correction. Fourth-dose responses were predicted by exponential modeling. Results: Of 631 participants, 524 completed primary immunization, 418 received a third dose (173 with complete data), and 56 received a fourth dose (22 with complete paired data). Local reactions declined from 82.4% after the first dose to 42.9% after the fourth (p < 0.001). Systemic reactions peaked at 44.8% after the second dose, then decreased to 26.0% after the third and 19.6% after the fourth. In contrast, median antibody levels rose from 9910 AU/mL after the primary series to 29,002 AU/mL after the third and 38,274 AU/mL after the fourth. Correlations between reactions and antibody titer progressively weakened: r = 0.37 (95% CI 0.29–0.44, p < 0.001) after the primary series, r = 0.08 (95% CI −0.07 to 0.23, p = 0.30) after the third, and r = 0.04 (95% CI −0.39 to 0.45, p = 0.86) after the fourth dose. Conclusions: Progressive dissociation between reactogenicity and immunogenicity was observed across four BNT162b2 doses. Booster doses maintain robust antibody responses despite reduced reactogenicity, reinforcing that minimal side effects are consistent with sustained humoral responses. Full article

Background: Pembrolizumab is a novel immunotherapy agent that improves oncological outcomes for various cancers. This study aimed to investigate immune-related adverse events (irAEs) that occurred after neoadjuvant chemotherapy (NAC) with pembrolizumab for triple-negative breast cancer (TNBC) and to identify fatal irAEs that should be addressed before surgery under general anesthesia. Methods: A total of 82 patients who received NAC with pembrolizumab followed by surgery were reviewed based on their medical records. All irAEs during NAC were evaluated and classified into nine categories: systemic, dermatologic, central nervous, musculoskeletal, endocrine, gastrointestinal, respiratory, ocular, and hematologic systems. Clinicopathologic characteristics were compared between patients with and without irAEs, and cases in which surgery was postponed due to irAEs were reviewed and analyzed. Results: Fifty-nine patients (72.0%) experienced irAEs after NAC with pembrolizumab. The mean NAC period was 140.3 days, with a 39.8-day window to surgery. The most common and second most common irAEs were myalgia (n = 33, 40.3%) and skin rash/dermatitis (n = 31, 37.8%), respectively. There were 1 case (1.2%) of adrenal insufficiency and 16 cases (19.5%) of thyroid dysfunction as irAEs. In 6 cases (7.3%), surgery was postponed due to irAEs [systemic (n = 2, 33.3%); endocrine (n = 3, 50.0%); increased transaminase (n = 1, 16.7%)], with a mean delay of 64.5 days (range, 57–80 days). Conclusions: IrAEs following NAC with pembrolizumab in TNBC were diverse and included those severe enough to affect the timing of surgery under general anesthesia. These irAEs should be monitored continuously during NAC and detected early to address them when they occur. Full article

Background/Objectives: Temporomandibular disorders (TMDs) are a group of multifactorial conditions affecting the temporomandibular joints (TMJs), masticatory muscles, and associated structures. TMDs are identified as the main cause of non-dental orofacial pain in children and adolescents. This scoping review aims to explore recent evidence on prevalence, clinical presentation, associated factors, and treatment approaches of TMDs in children and adolescents. Methods: A systematic search was conducted across PubMed, Scopus and Embase for studies published between 2015 and 2025, following PRISMA-ScR guidelines. Results: Thirty-eight studies were included. TMD prevalence in children and adolescents ranged from 16.9% to 40% through clinical examination, with painful TMD rates ranging from 16.2% to 25.5%, while symptom-based surveys reported prevalences of 9–35.3%. The most frequent diagnoses were myofascial pain, myalgia, arthralgia and disc displacement with reduction. Female sex and increasing age were consistent risk factors. Psychosocial variables, such as anxiety and depression, showed strong associations with pain-related TMDs. Structural and systemic conditions such as musculoskeletal alterations, joint hypermobility, respiratory conditions and headaches/migraines were also frequently reported. Evidence on treatment appears to be limited. In juvenile idiopathic arthritis (JIA), TMJ involvement is prevalent (32.6–64%), particularly in the persistent oligoarticular subtype. Conclusions: TMDs in children and adolescents are prevalent and multifactorial conditions, mainly of muscular origin, presenting more frequently in adolescents and females. Psychosocial factors, functional habits, clenching, mouth breathing and systemic conditions may be associated with TMD presence or severity. Substantial heterogeneity persists in diagnostic criteria, assessment tools and outcome measures. Research on therapeutic interventions is scarce and often limited to small samples. Standardized diagnostic protocols, improvements in research consistency, longitudinal cohorts and RCTs are needed to clarify etiological pathways, validate diagnostic criteria and establish effective, evidence-based strategies for the management of TMDs in children and adolescents. Full article

Introduction: Disc displacement with reduction (DDwR) and myalgia are among the most common temporomandibular disorders, frequently affecting young adults. While conservative therapy is considered the first-line approach, the evidence on long-term outcomes is still limited. Case Presentation: A 22-year-old female had a 7-month history of left-sided TMJ clicking, deviation to the left during opening, and 2 months of bilateral masticatory pain, which was worsened by mastication. During clinical examination, reproducible left TMJ clicking and tenderness of the masseter and temporal muscles were observed. Based on DC/TMD Axis 1, DDwR with myalgia diagnosis was made. Intervention and Results: A full maxillary stabilization splint was constructed and delivered together with patient education, dietary adjustments, and guided mandibular exercises. At baseline, pain intensity was VAS 6/10 with a maximum unassisted mouth opening of 41 mm and reproducible joint clicking. After 2 weeks, the patient reported a decrease in pain, VAS 2/10, mouth opening was 44 mm, and joint sounds were absent. After 1 year, the patient was asymptomatic (VAS 0/10) with stable function, preserved mouth opening, and completion of daily activities without limitations. Clinical Relevance and Conclusions: This case shows that multi-directional non-invasive therapy can result in complete and long-term remission of DDwR with myalgia. It emphasizes the need for careful diagnosis, through standardized instruments such as DC/TMD, and the need for personalized treatment to ensure durable clinical success. Full article

Background/Objectives: The COVID-19 pandemic led to profound lifestyle changes and long-term functional consequences, particularly among individuals with chronic respiratory diseases. Patients with asthma and chronic obstructive pulmonary disease (COPD) may be especially vulnerable to reductions in physical activity and persistent post-COVID-19 symptoms. This study aimed to compare lifestyle characteristics, physical activity levels, and post-COVID-19 symptom persistence in patients with asthma and COPD with those of individuals without chronic disease in the post-pandemic period. Methods: This national, multicenter, cross-sectional study was conducted in 2022 at five pulmonary outpatient clinics. Participants were categorized into three groups: asthma (n = 165), COPD (n = 82), and individuals without chronic disease (n = 431). Demographic and clinical data were collected through face-to-face structured interviews. Physical activity levels were assessed using the short form of the International Physical Activity Questionnaire and expressed as metabolic equivalent of task (MET) scores before and after the pandemic. Dyspnea severity was evaluated using the modified Medical Research Council scale. COVID-19 history, disease severity, and persistent symptoms were recorded. Results: A total of 678 participants were included. The median age was highest in the COPD group (68 (61–74) years), followed by the asthma group (54 (42–64) years) and individuals without chronic disease (38 (27–50) years). Female sex predominated among patients with asthma (77%), whereas male sex was more frequent in the COPD group (83%); sex distribution was similar among individuals without chronic disease (51% female). Across all groups, post-COVID-19 symptoms—including dyspnea, cough, fatigue, and myalgia—persisted for at least six months after infection. Physical activity levels, assessed by metabolic equivalent of task (MET) scores, declined significantly in the post-pandemic period in all groups, with the lowest levels observed in patients with COPD. COVID-19 severity and hospitalization rates were higher in patients with COPD, while intensive care unit admission rates were comparable between patients with asthma and individuals without chronic disease. Conclusions: In the post-pandemic period, physical activity levels declined markedly, and lifestyle changes were negatively affected in patients with asthma and COPD. Post-COVID-19 symptoms persisted longer than expected even in those without chronic disease. Therefore, individualized home-based exercise programs and psychosocial support should be considered to improve physical activity and quality of life, particularly in patients with chronic respiratory diseases, while preventive strategies should also be implemented at the population level. Full article

Murine typhus (also called flea-borne or endemic typhus) is an undifferentiated febrile illness caused by the bacterium Rickettsia typhi. The disease, transmitted by rat and cat fleas, is endemic to seaboard regions worldwide. Recently, murine typhus has reemerged as an increasingly recognized cause of febrile illness in the United States, especially in Texas and Southern California. In addition to fever, manifestations often include headache, malaise, myalgias, and a maculopapular rash in approximately half of cases. Although usually considered a mild illness, when untreated, symptoms can last up to 3 weeks. Severe manifestations such as pneumonitis, acute kidney injury, and meningoencephalitis may occur. Historically, death has occurred in 0.4%, but in Southern California, the case fatality rate has been recently recorded at 1.8%. As murine typhus has reemerged, there have been growing reports that this infection has triggered hemophagocytic lymphohistiocytosis, a life-threatening hyperinflammatory syndrome. We herein report two fatal cases of hemophagocytic lymphohistiocytosis secondary to murine typhus. Autopsy revealed typhus group rickettsial antigen in tissues via immunohistochemistry, along with hemophagocytosis. Interestingly, the classic vascular and perivascular histopathologic findings associated with disseminated rickettsial infection were absent. These findings highlight an aberrant inflammatory cascade leading to hemophagocytic lymphohistiocytosis. Full article

Oropouche virus (OROV) has emerged as a significant arboviral pathogen in South America, responsible for recurrent outbreaks of febrile illness. In the Loreto region of Peru, more than 600 cases were reported in 2024, markedly exceeding expected incidence rates. We conducted a retrospective observational study using clinical–epidemiological records of all RT-qPCR-confirmed cases of Oropouche fever from the Regional Health Directorate of Loreto between October 2024 and March 2025. A total of 100 confirmed cases were identified. The most frequent symptoms were fever (88%), headache (78%), and myalgia (72%). No atypical or neurological presentations were reported. No severe cases or deaths occurred. Eight patients required hospitalization, mainly due to severe abdominal pain, persistent vomiting, arthralgia, and pregnancy. Six pregnant women were identified; three experienced pregnancy complications, though no fetal malformations or miscarriages were observed. This outbreak represents a new OROV epidemic in the region, with fewer cases than in 2024 and predominantly mild clinical courses. Although outcomes were generally favorable, the occurrence of complications in pregnant women underscores the importance of continued molecular surveillance and targeted public health interventions. Full article

Background and Clinical Significance: Isolated mediastinal lymphadenopathy is an exceptionally rare and diagnostically challenging initial manifestation of microscopic polyangiitis (MPA), often mimicking malignancy or infection. This case highlights the pivotal role of an innovative minimally invasive technique in achieving a definitive diagnosis. To the best of our knowledge, this is the first reported case of MPA diagnosed via EBUS-TMC. Case Presentation: A 55-year-old male livestock farmer from a rural area with a history of recurrent pneumonia presented with four weeks of persistent fever, significant weight loss (7 kg), myalgia, and asthenia. Physical examination revealed fever and cachexia. Notable findings included leukocytosis (17,000/μL), normocytic anemia, thrombocytosis (672,000/μL), highly elevated inflammatory markers (CRP 145 mg/L, ESR 120 mm/h), and strongly positive MPO-ANCA (>134 U/mL). Serological testing was significant for IgG antibodies against Coxiella burnetii (Phase I 1:64, Phase II 1:256). PET-CT imaging demonstrated hypermetabolic bilateral hilar and mediastinal lymphadenopathy. Diagnostic challenges included overlapping serological findings suggestive of past Coxiella burnetii exposure. Endobronchial ultrasound–guided transbronchial mediastinal cryobiopsy (EBUS-TMC) of a subcarinal lymph node was performed, providing a high-quality sample that revealed neutrophilic small-vessel vasculitis with fibrinoid necrosis, definitive for MPA. Immunosuppressive therapy with high-dose corticosteroids and rituximab (1000 mg on days 1 and 15) was initiated, leading to the complete resolution of all constitutional symptoms. Conclusions: This case illustrates that EBUS-TMC is a safe and highly effective diagnostic tool for obtaining critical histological evidence in systemic vasculitides with atypical presentations. This technique should be considered in the diagnostic algorithm for unexplained mediastinal lymphadenopathy to avoid more invasive surgical procedures. Full article

Background: Some patients suffer from persistent symptoms following a COVID-19 infection, referred to as long COVID. The aims of the study were to estimate the prevalence of long COVID and study its determinants in Tunisia. Methods: We conducted a nationwide cross-sectional study among a representative sample of COVID-19 survivors residing in Tunisia between June and August 2022. We selected a random sample, stratified by age and region, among residents registered in the national surveillance database with a SARS-CoV-2 positive test taken from September 2020 to September 2021 (n = 479,743). The expected sample size was 384. We defined a patient with long COVID as having at least one self-reported symptom persisting for more than four weeks after the first confirmation of SARS-CoV-2 infection (RT-PCR or Ag-RDT) and not explained by an alternative diagnosis. Trained healthcare workers interviewed consenting respondents by phone using a structured questionnaire. We described continuous variables using median and interquartile range (IQR). We measured the prevalence of long COVID and its 95% confidence interval (95% CI). We estimated the association between explanatory variables (socio-demographic, lifestyle and comorbidities, SARS-CoV-2 history infection, COVID-19 vaccination status) and long COVID using a log-binomial model, reporting adjusted prevalence ratios (a-PR) and its 95% CI. Results: Of 1094 persons contacted, 416 were enrolled (response rate: 38%). Long-COVID prevalence was 64% (267/416); 95% CI [59–69%]. The sex ratio (M:F) was 0.72. Age ranged from 1 to 101 years, with a median of 41 years (IQR:31–55 years). The most common symptoms were fatigue (63%), myalgia/arthralgia (33%), and cognitive symptoms (52%). Median duration of long-COVID symptoms was 11 months (IQR: 3–14 months). In multivariate analysis, experiencing acute COVID-19 (a-PR = 1.5; 95% CI [1.0–2.1]), being a woman of childbearing age (a-PR = 1.2; 95% CI [1.0–1.4]) and residing in the central region (a-PR = 1.5; 95% CI [1.1–2.0]) were significantly associated with a higher prevalence of long COVID. Conclusions: Long COVID is prevalent in Tunisia affecting patients with multiple symptoms initially, those residing in the central region and young women. We recommend to enhance healthcare access and medical follow-up both during and after the infection, focusing on identified risk groups. We also recommend to conduct further research to optimize management of long-COVID patients. Full article

Background and Clinical Significance: Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders that may present as paraneoplastic syndromes. Although most frequently associated with solid-organ malignancies, hematological neoplasia, particularly lymphomas, is also likely linked. Case Presentation: We describe a sexagenarian female with progressive proximal muscle weakness, myalgias, and lymphadenopathy. Laboratory evaluation revealed markedly elevated creatine phosphokinase and myositis-specific antibodies: anti-Mi-2α and anti-EJ. Magnetic resonance imaging of the thighs confirmed active myositis. Lymph node biopsy reported follicular lymphoma. The patient was initiated on methotrexate and rituximab, with which she reported significant symptomatic relief. Conclusions: Inflammatory myopathy is an exceedingly rare presentation of follicular lymphoma. This case emphasizes that lymphomas can closely mimic other disease processes and present significant diagnostic challenges, and they should be included in the differential diagnosis of myopathies. Improved awareness and early diagnosis of lymphoproliferative neoplasia often yield better overall clinical outcomes. Full article

Background and Clinical Significance: Statins are widely prescribed for cardiovascular risk reduction and generally demonstrate a favorable safety profile. While myalgia and elevations in liver enzymes are well-recognized adverse effects, headaches are less commonly reported and often underrecognized in clinical practice. This may result in unnecessary diagnostic evaluations, increased healthcare costs, and delayed identification of the underlying cause. Case Presentation: We describe an adult patient who developed intractable headaches that emerged after many years of statin therapy. The headaches persisted despite conventional analgesic treatment and resolved completely following discontinuation of the statin. Secondary causes were excluded, and comorbid conditions were systematically ruled out. Statin-associated headache is uncommon but clinically relevant. Proposed mechanisms include nitric-oxide-mediated vasodilation, central effects of lipophilic statins, and mitochondrial involvement. In this case, the patient was taking metoprolol succinate, lisinopril, simvastatin, clopidogrel, and tamsulosin. Except for lisinopril, none of the other comedications are strongly linked to new-onset headaches. Holding it did not resolve his headache, making simvastatin the most plausible contributor. This was confirmed by resolution of headache through its discontinuation. Because such headaches may be overlooked, clinicians should consider a statin-related cause when symptoms begin after initiation and may manage this by switching to a hydrophilic statin or using alternative lipid-lowering therapy. Conclusions: Clinicians should remain vigilant about the possibility of statin-induced headache, even in long-term users. Early recognition can prevent unnecessary diagnostic investigations, expedite symptom resolution, and support optimal management of both cardiovascular risk and treatment-related adverse effects. Full article

Influenza and other respiratory viruses pose significant public health threats among SARI patients, yet comprehensive surveillance data remain limited in Pakistan. This prospective, multi-center study characterized the burden, distribution, and molecular evolution of respiratory viruses among hospitalized SARI patients across seven tertiary hospitals from November 2022 to June 2025. Specimens were tested using RT-PCR for influenza, SARS-CoV-2, and RSV, with 375 samples sequenced via Oxford Nanopore Technology. Among 11,451 specimens, 2818 (24.6%) tested positive: RSV (1648, 14.4%), influenza (855, 7.5%; 45% H1N1pdm09, 35% H3N2, 20% influenza B), and SARS-CoV-2 (315, 2.8%). RSV predominantly affected children under 2 years (63%), while influenza and SARS-CoV-2 primarily impacted adults aged 15–40 years. Male predominance (65–79%) reflected healthcare access barriers. Strong winter seasonality (December–February) was observed for influenza and RSV. ICU admission rates were 17% for influenza, 16% for RSV, and 4% for SARS-CoV-2. Shortness of breath was associated with influenza (OR = 1.62) and RSV (OR = 1.27), while malaise (OR = 2.24) and myalgia (OR = 3.87) was associated with SARS-CoV-2. Phylogenetic analysis revealed vaccine-matched influenza clades and rapid SARS-CoV-2 variant succession (3–4 months). RSV is the primary SARI pathogen in young children, necessitating maternal vaccines and nirsevimab implementation. Sustained genomic surveillance remains essential for pandemic preparedness. Full article

Background: Temporomandibular disorders (TMDs) are the most common source of non-dental orofacial pain, with peak prevalence during adolescence and young adulthood—the same age group when orthodontic treatment is typically initiated. Although orthodontics is not a proven cause of TMD, pre-existing dysfunction may be aggravated during treatment, creating clinical and medico-legal risks. Objective: This paper proposes a structured diagnostic questionnaire and scoring framework for pre-orthodontic TMD assessment. The protocol aims to enhance the early recognition of high-risk patients, facilitate interdisciplinary communication, and lay a foundation for systematic validation. Methods: The framework was developed through synthesis of international diagnostic criteria (DC/TMD), a targeted narrative review of the literature, and expert clinical input. Diagnostic categories were selected based on prevalence, impact on orthodontic outcomes, and medico-legal significance. Weighted scoring stratifies patients into three pathways: (1) proceed with orthodontics without concern, (2) proceed with monitoring, or (3) defer orthodontics until TMD is managed. Results: The proposed questionnaire is designed to address inconsistencies in the literature by applying standardized diagnostic items and objective thresholds (e.g., jaw opening < 38 mm) and structured follow-up intervals. Case scenarios illustrate how risk stratification guides decision-making. The questionnaire includes intra-articular and pain-related TMD entities such as disk displacement, degenerative joint disease, myalgia, myofascial pain, arthralgia, headache, and trismus. The framework provides orthodontists with defensible baseline documentation while supporting safe and individualized patient care. Conclusions: Inconsistent diagnostic frameworks, malocclusion classifications, and outcome measures have fragmented the evidence base in orthodontics and TMD. The framework aims to provide orthodontists with structured baseline documentation that may support clinical decision-making and medico-legal risk management. Validation studies are required to establish psychometric reliability and international applicability. Full article

Background: The global incidence of dengue has markedly increased over the last decades. Consequently, the risk of infection has increased significantly, resulting in record numbers of imported cases in various European countries and elsewhere in 2024. Methods: In early 2023, TAK-003, a novel, live attenuated vaccine against dengue, became available in Germany. At the Berlin Centre for Travel & Tropical Medicine, we delivered 56,459 doses during the first 24 months of its availability, from February 2023 to February 2025. To obtain data on the tolerability of the vaccine in travelers, an active follow-up survey was initiated. Results: In total, 30,306 (53.7%) vaccinees agreed to being contacted. Of these, 11,827 (39.0%) completed an anonymous questionnaire ≥ 4 weeks after the vaccination. Overall, 6856 (58.0%) were female, and 565 (4.8%) reported having had a prior dengue infection. The average age was 38.3 years (range 4–86 years). An endemic area had been visited by 6309 subjects before answering the questionnaire, and among these, 46 (0.7%) reported a dengue infection while abroad. All cases were mild, and no complications were reported. TAK-003 was applied with other vaccines in 7363 (62.3%) travelers. Local adverse reactions, mostly local pain, were reported by 5263 (47.5%) subjects. Systemic reactions were reported by 4891 subjects (41.4%) and were most frequently fatigue, myalgia, and flu-like symptoms. The majority of adverse events manifested in the second week after vaccination (median 8 days) and were mostly limited to a duration of 1–3 days. A macular exanthema was described by 1844 subjects (15.6%), typically during the second week after the vaccination. Conclusions: Side effects were frequently reported but generally well tolerated. Age groups above 50 years showed a decline in reactogenicity. Co-vaccination was frequent and led to an increase in systemic adverse events. Denominator data of the study population suggest a strong reporting bias towards adverse events. This survey adds evidence of the chronology and characteristics of adverse events associated with TAK-003 and may support decision making when vaccinating dengue-naïve travelers. Full article

Background/Objectives: Muscle biopsy is traditionally considered a cornerstone in the diagnosis of myopathies. Advances in the clinical and laboratory evaluation of myopathies warrant re-evaluation of the diagnostic yield. Methods: Results of muscle biopsies performed between 1 January 2009 and 31 January 2023 in patients with symptoms indicative of myopathy were evaluated and set in relation to clinical diagnosis, based on phenotype, electromyography, laboratory results, and available antibody testing. Biopsies were classified as diagnostic (changed or specified clinical diagnosis), confirmative (same as clinical diagnosis), or non-informative (normal/unspecific findings). Genetic testing followed muscle biopsy at later follow-up, upon availability of genetic testing. Results: One-hundred sixty-two patients were included and divided into five groups based on clinical phenotype: inflammatory myopathy, n = 54; mitochondrial myopathy, n = 33; muscular dystrophy, n = 23; metabolic myopathy, n = 3; and non-specific phenotype (isolated hyperCKemia/myalgia), n = 49. Muscle biopsy was diagnostic in 21.0%, confirmative in 38.3% and non-informative in 40.7% of patients. The percentage of diagnostic biopsies was 66.7% in metabolic myopathy, 54.5% in mitochondrial myopathy, 17.4% in muscular dystrophy, 14.8% in inflammatory myopathy, and 4.1% in the non-specific phenotype. Conclusions: Overall, in our cohort, muscle biopsy yielded a new diagnosis or additional information in 21.0% of patients. In the majority, a diagnosis was established based on clinical and laboratory evaluation, and muscle biopsy was either confirmative or non-informative. We propose muscle biopsy in cases where serological and genetic tests are inconclusive, in the presence of specific signs indicative of myopathy, or when in-tissue genetic testing is necessary to obtain a comprehensive diagnosis. Full article