Background/Objectives: Human papillomavirus (HPV) is the most common sexually transmitted virus worldwide and is frequently detected in women of reproductive age. In this population, HPV-related diseases and their management may affect reproductive health and pregnancy outcomes. This narrative review summarizes the current evidence on HPV infection and HPV-related diseases in relation to fertility, pregnancy, and neonatal outcomes, and discusses preventive strategies, with a particular focus on HPV vaccination. Methods: An international, multidisciplinary team of clinicians from the European Society of Gynaecological Oncology (ESGO) Prevention Committee reviewed the literature on HPV, HPV-related diseases, HPV vaccination, and reproductive outcomes, without time restrictions, prioritizing studies judged to meaningfully reflect the available evidence. Results: The most consistent evidence linking HPV-related conditions to adverse pregnancy outcomes relates to the treatment of cervical precancer, particularly excisional procedures, which are associated with an increased risk of preterm birth and mid-trimester pregnancy loss. In contrast, evidence that maternal HPV detection alone causes adverse pregnancy or neonatal outcomes remains limited and inconsistent. Data on HPV infection and subfertility are scarce and heterogeneous. Management of HPV-related lesions during pregnancy remains challenging and requires careful balancing of maternal safety with avoidance of unnecessary interventions. HPV DNA has been detected in neonatal samples, but convincing evidence for clinically relevant vertical transmission is lacking. Available data indicate that inadvertent HPV vaccination shortly before or during pregnancy is not associated with adverse pregnancy outcomes. Conclusions: Current evidence suggests that reproductive risks are more strongly associated with the treatment of HPV-related diseases than with HPV infection itself. Preventive strategies—especially HPV vaccination—remain central to reducing HPV-related disease burden. Although HPV vaccines are not routinely recommended during pregnancy, evidence supports the safety of inadvertent exposure around conception or during gestation, while potential long-term benefits of vaccination regarding reproductive health require further study.
Glucagon is a key regulator of amino acid metabolism, and elevated levels are frequently observed in maintenance hemodialysis (MHD) patients. Yet, the relationship between plasma glucagon levels, nutritional parameters, and prognosis in MHD patients remains unclear. We evaluated whether glucagon levels in MHD patients are associated with normalized protein catabolic rate (nPCR), glucagon-like peptide-1 (GLP-1), nutritional status, and all-cause mortality. In this prospective observational study, plasma hormone levels were measured alongside clinical, biochemical, anthropometric, bioimpedance-derived nutritional markers, and inflammatory indices. Mortality was assessed using Kaplan–Meier and Cox regression analyses. This study included 82 prevalent MHD patients. Patients were followed for 18.0 ± 4.9 months. Glucagon correlated positively with nPCR (r = 0.25, p = 0.03) and inversely with phase angle (PhA) (r = − 0.24, p = 0.03) after adjustment. Additional correlations with GLP-1 became marginal after adjustment. The subgroup with high glucagon and low nPCR showed the lowest PhA (p = 0.03), and remained significant after multivariable adjustment. Patients with glucagon ≥ 120 pg/mL (ROC-derived cutoff) had higher mortality (log-rank p = 0.05); however, the discriminative power of this cutoff was limited (AUC 0.63). In multivariable models, the association persisted after adjustment for age and diabetes but was attenuated after further controlling for PhA, GLP-1, or MIS. Elevated glucagon in MHD patients was modestly associated with altered protein metabolism, impaired nutritional integrity, and borderline higher all-cause mortality. The independent prognostic value of glucagon remains uncertain, and a concept of a glucagon resistance phenotype is speculative.
Background The potential of walnut oral immunotherapy (OIT) to cross-desensitize for hazelnut has been anecdotally reported. Objective To identify rates and predictors of hazelnut cross-desensitization following walnut OIT. Methods A prospective cohort study was conducted in the Institute of Allergy at the Shamir Medical Center between July 2016 and July 2021. The rate of hazelnut cross-desensitization in walnut-hazelnut coallergic patients aged 4 years or older following walnut OIT was compared with hazelnut allergy resolution in observational controls. Immunologic markers at baseline and following walnut desensitization were examined, and clinical and molecular predictors of cross-desensitization were sought. Results Hazelnut cross-desensitization occurred in 53 of 99 (53.5%) patients who began walnut OIT, and in 53 of 80 (66.2%) walnut-desensitized patients challenged for hazelnut, compared with 3 of 19 (15.8% resolution rate) controls (odds ratio [OR], 6.1, 95% CI, 1.7-22.4, P = .003, and OR, 10.5, 95% CI, 2.8-39.1, respectively). Immunologic desensitization (decreased hazelnut sensitization and basophil reactivity, and increased specific IgG4) followed. On multivariate analysis, a higher hazelnut skin prick test wheal diameter (OR, 1.28, 95% CI, 1.07-1.54, P = .008) and a hazelnut reaction dose of 60 mg or less (OR, 8.3, 95% CI, 2.0-34.5, P = .003) at baseline predicted persistent hazelnut allergy. Baseline specific IgE levels greater than or equal to 7 kUA/L to Cor a 14, but not to Cor a 9 and 16, were associated with persistent hazelnut allergy. Cor a 14–specific IgG4 significantly increased only in cross-desensitized patients, whereas Cor a 9– and Cor a 16–specific IgG4 increased in persistent hazelnut-allergic patients, as well. Conclusions Most walnut-hazelnut–allergic patients benefit from single walnut OIT. Lower hazelnut sensitization and a higher reaction dose predict cross-desensitization. Cor a 14 plays a role in persistent hazelnut allergy.
Objective Temporal bone dissection poses a significant challenge due to its intricate three-dimensional (3D) anatomy. Traditional learning methods involving cadaver dissections are limited by practical constraints. Augmented reality (AR) offers a potential solution by providing 3D anatomical visualization of key anatomical landmarks based on computed tomography (CT) scans, superimposed directly onto the cadaver specimen. This pilot study evaluated the feasibility of integrating AR to support temporal bone dissection of cadavers and enhance otolaryngology residents' grasp of anatomy.Methods Four otolaryngology residents performed a total of seven temporal bone dissections during a dedicated dissection course. AR models were developed using specimen-specific CT data and overlaid onto cadaveric specimens using the Microsoft HoloLens 2 headset. Participants' dissection accuracy and efficiency were evaluated using predefined metrics, and their feedback was collected through questionnaires to assess the system's contribution to learning.Results In this pilot feasibility study, the AR system was successfully integrated into the dissection workflow, with participants reporting improved understanding of these complex anatomical structures as well as enhanced spatial orientation. Dissection quality was high, and the participants expressed overall satisfaction with the course.Conclusion AR technology shows significant potential as an adjunct to traditional temporal bone dissection training by providing enhanced visualization that leads to greater anatomical understanding.Level of Evidence N/A.
Abstract Introduction Gestational diabetes mellitus (GDM) is associated with increased neonatal morbidity in singleton pregnancies, but evidence in multifetal pregnancies is limited. Current diagnostic thresholds are largely extrapolated from singleton data; It remains unclear whether plurality modifies GDM‐associated neonatal and long‐term offspring outcomes. We wanted to evaluate neonatal complications and long‐term offspring healthcare utilization associated with GDM in multifetal versus singleton pregnancies, and to assess effect modification by plurality and the impact of gestational age at delivery. Material and Methods This multicenter retrospective cohort study utilized electronic medical records across six university‐affiliated medical centers in Israel (1/1/2010–6/30/2024). All live births at 22 weeks' gestation or later or with birthweight of >500 g were included. Four exposure groups were defined by plurality and GDM status (ICD‐9 code 648.8x): singleton without GDM, singleton with GDM, multifetal without GDM, and multifetal with GDM. Short‐term neonatal complications (neonatal hypoglycemia, neonatal ICU admission, respiratory distress, intraventricular hemorrhage, and growth abnormalities) and long‐term offspring outcomes were assessed by hospital‐based health‐care utilization (e.g., neurology, ophthalmology, cardiology). Multivariable Firth logistic and ordinary least squares regression models were adjusted for maternal age, body mass index, parity, and fertility treatment. Additional models adjusted for gestational age were performed. False discovery rate correction and GDM‐by‐plurality interaction terms were applied. Results Of 134 517 pregnancies (136 579 live‐born offspring) to 104 023 mothers, 10 605 singleton (7.9%) and 256 multifetal (0.2%) pregnancies were complicated by GDM. In multifetal pregnancies, GDM was not associated with increased short‐term neonatal complications nor with lower adjusted odds of neonatal hypoglycemia (adjusted odds ratio [aOR], 0.30; 95% CI: 0.18–0.49), neurologic (aOR, 0.37; 95% CI: 0.24–0.59), or ophthalmologic (aOR, 0.49; 95% CI: 0.31–0.77) health‐care utilization. Adjustment for gestational age attenuated associations for neonatal intensive care unit admission but did not fully explain interactions for hypoglycemia or selected long‐term outcomes. Conversely, GDM in singleton pregnancies was associated with increased neonatal morbidity. Conclusions Associations between GDM and neonatal and offspring outcomes differ by plurality. Risk stratification strategies derived from singleton pregnancies may not fully capture risk profiles in multifetal pregnancies.
