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IntroductionAs personalized medicine advances, the need to explore periodontal health across different sexes and gender identities becomes crucial. This narrative review addresses the gap in understanding how biological sex and gender-affirming hormone therapy (GAHT) influence periodontitis risk.ResultsResearch has uncovered significant sex-based immunological disparities driven by X and Y chromosome gene expression and sex-hormones, which may influence susceptibility to periodontitis. Additionally, preliminary findings suggest that GAHT, particularly testosterone therapy in transgender men, could exacerbate pro-inflammatory cytokine production and alter immune cell responses, which may exacerbate inflammatory pathways crucial in the progression of periodontitis. Conversely, the effects of estrogen therapy in transgender women, although less extensively studied, suggest modifications in B cell functionality. These observations highlight the complex role of GAHT in modulating immune responses that are central to the development and exacerbation of periodontal disease.DiscussionThe review highlights a complex interaction between sex hormones, gene expression patterns, immune responses, and periodontitis risk. While cisgender males show increased susceptibility to periodontitis that could be linked to specific immune pathways, GAHT appears to modify these pathways in transgender individuals, potentially altering their risk and disease progression patterns.ConclusionThere is a critical need for more focused research on the direct impacts of GAHT on periodontal health. Understanding the nuances of immune modulation by GAHT will aid in crafting personalized periodontal care for transgender individuals, aligning with the broader goals of inclusive and effective healthcare.

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by a variety of both signs and symptoms; it mainly affects women of childbearing age, with an estimated prevalence of 24/100,000 people in Europe and North America. SLE is often described as an antibodies-driven disease as its clinical manifestations are usually associated with the presence or the absence of specific antibodies.ObjectivesTo evaluate clinical manifestations in patients with SLE and to assess the relationship with the presence of specific antibodies by using real-world data.MethodsA retrospective study was performed; the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus were used to classify patients with SLE. Data concerning serological profiles (which included Antinuclear antibodies – ANA, anti dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-Smith) were gathered along with medical records of clinical manifestations. Complement levels were also tested for possible clinical correlations. χ² or Fisher’s exact tests were utilized to establish associations between autoantibodies and symptoms. The odds ratios (OR) and their 95% confidence intervals (CI) were computed. No correction was made for multiple testing; only a p-value 0.01 ≤ was considered significant.ResultsOne-hundred and twenty-seven patients (n=127, mean age 53.43 ± 14.02) were enrolled in this study. Anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies showed an association with photosensitivity and pericarditis; furthermore, a strong association was found between anti-Ro antibodies and proteinuria, but only if anti-dsDNA antibodies were present as well. Patients who tested positive for anti-La/SSB antibodies correlated with a threefold increase in the risk of developing pericarditis. Lastly, anti-Smith appeared to be associated with NPSLE as well as an increased risk for both autoimmune hemolytic anemia and thrombocytopenia.ConclusionsIn our study, many associations confirmed those found in previous studies; however, new relationships between antibodies and clinical manifestations were found thus indicating the need for additional evaluations to assess these correlations further.

MRI-guided focused ultrasound (MRgFUS) lesioning is an innovative, safe and effective treatment which provides an innovative development in the field of minimally invasive stereotactic neurosurgery. Based on the application of focused ultrasound energy under full MR planning and thermal imaging control, unilateral lesioning of the thalamus, subthalamic nucleus, and globus pallidus is indicated for the treatment of movement disorders, including essential tremor, Parkinson’s disease, and dystonia. We started to apply this technique in February 2019 for the treatment of patients with movement disorders. The authors developed a diagnostic therapeutic care pathway, which is herewith proposed and applied as an explication of standard clinical practice in use. The project was the result of the application of different methods such as Health Technology Assessment (HTA), Strengths, Weaknesses, Opportunities and Threats analysis (SWOT) and Demin -Plan, Do, Check, Act (PDCA) cycle. The aim of this project was to standardize the MRgFUS diagnostic-therapeutic pathway (DTP), describe its application and the appropriateness of different phases (patient selection, intervention phase and follow-up). Here, we described in detail our experience in the DTP application from 2019 up to now in 610 patients with movement disorders.

IntroductionAtrial fibrillation secondary to dilated cardiomyopathy (DCM) frequently affects large-breed dogs. The aim of the present study was to identify risk factors for the development of atrial fibrillation in dogs of different breeds with an echocardiographic diagnosis of DCM.MethodsIn this multicenter retrospective study, we searched the electronic databases of five cardiology referral centers for dogs with an echocardiographic diagnosis of DCM. A comparison of clinical and echocardiographic variables was performed between dogs developing atrial fibrillation and those not developing atrial fibrillation and the ability to distinguish between these two groups of dogs was evaluated by receiver operating characteristic curve analysis. Univariate and multivariable logistic regression analysis estimated the odds ratio (OR) with 95% confidence interval (CI) of developing atrial fibrillation.ResultsWe included 89 client-owned dogs with occult and overt echocardiographic DCM. Of these, 39 dogs (43.8%) had atrial fibrillation, 29 dogs (32.6%) maintained a sinus rhythm, and 21 dogs (23.6%) showed other cardiac arrhythmias. Left atrial diameter had high accuracy (area under the curve = 0.816, 95% CI = 0.719–0.890) to predict the development of atrial fibrillation at the cut-off of >4.66 cm. After multivariable stepwise logistic regression analysis, only increased left atrial diameter (OR = 3.58, 95% CI = 1.87–6.87; p < 0.001) and presence of right atrial enlargement (OR = 4.02, 95% CI = 1.35–11.97; p = 0.013) were significant predictors of atrial fibrillation development.DiscussionAtrial fibrillation is a common complication of DCM in the dog and is significantly associated with increased absolute left atrial diameter and right atrial enlargement.

Food allergy is a global health problem affecting up to 10% of the world population. Accurate diagnosis of food allergies, however, is still a major challenge in medical offices and for patients seeking alternative avenues of diagnosis. A flawless test to confirm or rule out a food allergy does not exist. The lack of optimum testing methods to establish precise clinical correlations remains a major obstacle to effective treatment. Certain IgE measurement methods, including component testing, have received FDA clearance, but they have been used primarily as an analytical tool and not to establish clinical correlations. Most allergy tests are still carried out within the laboratory, and skin tests outside a laboratory setting that are used for food allergy diagnosis rely on non-standardized allergens, according to the FDA definition. Epitope mapping and basophil activation test (BAT) have recently been proposed as a means of establishing better clinical correlations. Yet neither have received FDA clearance for widespread distribution. Of the two methods, the BAT has the advantage of being a functional assay. Over the past few years, several large private practice groups in the United States, have developed BAT as a clinical assay and have started using it in patient care. Given this clinical experience, the vast number of papers published on BAT (more than 1,400 as of 2022) and the trend toward increasing FDA regulation, it is essential to understand the roadmap for regulatory clearance of this assay.

IntroductionFunctional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications. The study aimed to identify clinical subtypes of combined FMDs using a data-driven approach to overcome possible limits related to “a priori” classifications and clinical overlapping.MethodsData were obtained by the Italian Registry of Functional Motor Disorders. Patients identified with multiple or “combined” FMDs by standardized clinical assessments were selected to be analyzed. Non-hierarchical cluster analysis was performed based on FMDs phenomenology. Multivariate analysis was then performed after adjustment for principal confounding variables.ResultsFrom a study population of n = 410 subjects with FMDs, we selected n = 188 subjects [women: 133 (70.7%); age: 47.9 ± 14.4 years; disease duration: 6.4 ± 7.7 years] presenting combined FMDs to be analyzed. Based on motor phenotype, two independent clusters were identified: Cluster C1 (n = 82; 43.6%) and Cluster C2 (n = 106; 56.4%). Cluster C1 was characterized by functional tremor plus parkinsonism as the main clinical phenotype. Cluster C2 mainly included subjects with functional weakness. Cluster C1 included older subjects suffering from anxiety who were more treated with botulinum toxin and antiepileptics. Cluster C2 included younger subjects referring to different associated symptoms, such as pain, headache, and visual disturbances, who were more treated with antidepressants.ConclusionUsing a data-driven approach of clinical data from the Italian registry, we differentiated clinical subtypes among combined FMDs to be validated by prospective studies.

Surgical staging is essential in the management of ovarian cancers. This staging has traditionally been performed by laparotomy, but minimally invasive techniques are increasingly employed. Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) is a promising technique in the field of gynecological oncology. We report 2 cases of vNOTES surgical staging for suspicious ovarian tumors. We operated on 2 patients aged of 81 and 62 years for low-grade serous ovarian carcinoma and ovarian cystadenofibroma, respectively. We performed surgical staging with a pure vNOTES technique for the first patient and used a hybrid approach for the second. No intraoperative or postoperative complications were observed. We suggest that vNOTES is a feasible and effective approach to surgically manage early-stage ovarian cancers.

Deep brain stimulation (DBS) is used for the treatment of movement disorders, including Parkinson’s disease, dystonia, and essential tremor, and has shown clinical benefits in other brain disorders. A natural path for the improvement of this technique is to continuously observe the stimulation effects on patient symptoms and neurophysiological markers. This requires the evolution of conventional deep brain stimulators to bidirectional interfaces, able to record, process, store, and wirelessly communicate neural signals in a robust and reliable fashion. Here, we present the architecture, design, and first use of an implantable stimulation and sensing interface (AlphaDBSR System) characterized by artifact-free recording and distributed data management protocols. Its application in three patients with Parkinson’s disease (clinical trial n. NCT04681534) is shown as a proof of functioning of a clinically viable implanted brain-computer interface (BCI) for adaptive DBS. Reliable artifact free-recordings, and chronic long-term data and neural signal management are in place.

Plasmatic dimethylarginines, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are considered biomarkers of endothelial and renal dysfunction, respectively, in humans. We hypothesize that plasmatic concentration of dimethylarginines in dogs with myxomatous mitral valve disease (MMVD) is influenced by heart disease stage. Eighty-five client-owned dogs with MMVD, including 39, 19, and 27 dogs in ACVIM stages B1, B2, and C+D, respectively, and a control group of 11 clinically healthy dogs were enrolled. A prospective, multicentric, case-control study was performed. Each dog underwent a complete clinical examination, arterial blood pressure measurement, thoracic radiography, six-lead standard electrocardiogram, transthoracic echocardiography, CBC, biochemical profile, and urinalysis. Plasmatic concentration of dimethylarginines was determined through high-performance liquid chromatography coupled with tandem mass spectrometry. Median ADMA was significantly increased in dogs of group C+D (2.5 μmol/L [2.1–3.0]) compared to those of group B1 (1.8 μmol/L [1.6–2.3]; p < 0.001) and healthy dogs (1.9 μmol/L [1.7–2.3]; p = 0.02). Median SDMA was significantly increased in dogs of group C+D (0.7 μmol/L [0.5–0.9]) compared to those of groups B1 (0.4 μmol/L [0.3–0.5]; p < 0.001), B2 (0.4 μmol/L [0.3–0.6]; p < 0.01), and the control group (0.4 μmol/L [0.35–0.45]; p = 0.001). In the final multivariable analysis, ADMA and SDMA were significantly associated with left atrium to aorta ratio (p < 0.001), and creatinine (p < 0.001), respectively. Increased plasmatic concentrations of dimethylarginines suggest a possible role as biomarkers of disease severity in dogs with decompensated MMVD.

Changes of lipidic storage, oxidative stress and mitochondrial dysfunction may be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Although the knowledge of intracellular pathways has vastly expanded in recent years, the role and mechanisms of circulating triggering factor(s) are debated. Thus, we tested the hypothesis that factors circulating in the blood of NAFLD patients may influence processes underlying the disease. Huh7.5 cells/primary human hepatocytes were exposed to plasma from 12 NAFLD patients and 12 healthy subjects and specific assays were performed to examine viability, H2O2 and mitochondrial reactive oxygen species (ROS) release, mitochondrial membrane potential and triglycerides content. The involvement of NLRP3 inflammasome and of signaling related to peroxisome-proliferator-activating-ligand-receptor-γ (PPARγ), sterol-regulatory-element-binding-protein-1c (SREBP-1c), nuclear-factor-kappa-light-chain-enhancer of activated B cells (NF-kB), and NADPH oxidase 2 (NOX2) was evaluated by repeating the experiments in the presence of NLRP3 inflammasome blocker, MCC950, and through Western blot. The results obtained shown that plasma of NAFLD patients was able to reduce cell viability and mitochondrial membrane potential by about 48 and 24% (p < 0.05), and to increase H2O2, mitochondrial ROS, and triglycerides content by about 42, 19, and 16% (p < 0.05), respectively. An increased expression of SREBP-1c, PPARγ, NF-kB and NOX2 of about 51, 121, 63, and 46%, respectively, was observed (p < 0.05), as well. Those effects were reduced by the use of MCC950. Thus, in hepatocytes, exposure to plasma from NAFLD patients induces a NAFLD-like phenotype by interference with NLRP3-inflammasome pathways and the activation of intracellular signaling related to SREBP-1c, PPARγ, NF-kB and NOX2.

The frontal aslant tract (FAT) is a recently identified white matter tract connecting the supplementary motor complex and lateral superior frontal gyrus to the inferior frontal gyrus. Advancements in neuroimaging and refinements to anatomical dissection techniques of the human brain white matter contributed to the recent description of the FAT anatomical and functional connectivity and its role in the pathogenesis of several neurological, psychiatric, and neurosurgical disorders. Through the application of diffusion tractography and intraoperative electrical brain stimulation, the FAT was shown to have a role in speech and language functions (verbal fluency, initiation and inhibition of speech, sentence production, and lexical decision), working memory, visual–motor activities, orofacial movements, social community tasks, attention, and music processing. Microstructural alterations of the FAT have also been associated with neurological disorders, such as primary progressive aphasia, post-stroke aphasia, stuttering, Foix–Chavany–Marie syndrome, social communication deficit in autism spectrum disorders, and attention–deficit hyperactivity disorder. We provide a systematic review of the current literature about the FAT anatomical connectivity and functional roles. Specifically, the aim of the present study relies on providing an overview for practical neurosurgical applications for the pre-operative, intra-operative, and post-operative assessment of patients with brain tumors located around and within the FAT. Moreover, some useful tests are suggested for the neurosurgical evaluation of FAT integrity to plan a safer surgery and to reduce post-operative deficits.

Cancer patients are a population at high risk of contracting COVID-19 and, also of developing severe complications due to the infection, which is especially true when they are undergoing immunosuppressive treatment. Despite this, they had still to go to hospital to receive chemotherapy during lockdown. In this context, we have evaluated the psychological status of onco-hematological outpatients receiving infusion and not deferrable anti-neoplastic treatment for lymphoproliferative neoplasms, with the aim of both measuring the levels of post-traumatic symptoms, depression, and anxiety during the pandemic and also of investigating the perception of risk of potential nosocomial infection. The Impact of Event Scale-Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS) were administered to all patients. Moreover, patients were investigated about their worries regarding the impact of COVID-19 on their lives as onco-hematologic patients. Since the 2nd to the 29th April 2020 (during the first phase of the lockdown period in Italy), 77 outpatients were prospectively evaluated. They were diagnosed with non-Hodgkin's lymphoma, classical Hodgkin lymphoma, and Chronic lymphocytic leukemia/Small lymphocytic lymphoma. The mean age was 56.6 (range 22–85). We found that 36% of patients had anxiety (HADS-A), 31% depression (HADS-D), and 43% were above the cut-off for the HADS-General Scale; 36% fulfilled the diagnostic criteria for post-traumatic stress disorder (PTSD). Women and younger patients were found to be more vulnerable to anxiety and PTSD. The study firstly analyzes the psychological impact of the COVID-19 pandemic on the frail population of patients affected by lymphoproliferative neoplasms, to underly the importance of screening patients for emotional and distress conditions and then offering them psychological support.

Research Question: Does reproductive outcome differ among the various subgroups of poor ovarian responders according to the Bologna criteria?Design: This was a retrospective, cohort study including poor ovarian responders according to Bologna criteria, undergoing an ICSI cycle from January 2011 until December 2017. Patients were divided into four groups: (1) age ≥ 40 years and abnormal ovarian response test, (2) age ≥ 40 years, abnormal ovarian reserve test and one previous poor response to stimulation, (3) age ≥ 40 years and one previous poor response, (4) abnormal ovarian reserve test and one previous poor response.Result(s): Overall, 846 cycles in 706 Bologna poor ovarian responders were included: 310 cycles in group 1, 169 in group 2, 52 in group 3, and 315 in group 4. There were significant differences in age, antral follicle count, antimüllerian hormone, cycle cancellation rates, and number of retrieved oocytes between the four groups. Live birth and cumulative live birth rate differed significantly between groups and were highest in Group 4 [Live birth rate: 7.4% (1) vs. 4.1% (2) vs. 5.8% (3) vs. 13.4% (4), p = 0.001 and Cumulative live birth rate: 8.3% (1) vs. 4.1 % (2) vs. 9.6% (3) vs. 16.8% (4) p < 0.001]. The multivariate GEE analysis revealed that the number of MIIs and the Bologna criteria pattern were the variables which were significantly associated with cumulative live birth rate.Conclusion(s): Poor ovarian responders represent a heterogeneous population. The young subpopulation has a better clinical prognosis in terms of fresh and cumulative live birth rate.

Background: Bologna criteria poor ovarian responders have a very low prognosis. Although, it has been proposed that LH supplementation could be beneficial in women with previous hypo-response to FSH. There are no studies comparing the cumulative live birth rates (LBRs) between corifollitropin alfa (CFA) and highly purified human menopausal gonadotrophin (hp-hMG).Objective: To compare cumulative LBRs in Bologna poor ovarian responders undergoing ovarian stimulation with CFA followed by hp-hMG vs. hp-hMG alone in a GnRH antagonist protocol.Design: This is a retrospective cohort study. We included in total 917 poor responders fulfilling the Bologna criteria for poor ovarian response (POR) at a university-affiliated tertiary center from January 2011 until March 2017. Patients were administered either fixed daily doses of 300–450 IU of hp-hMG (group A) or a single dose of 150 μg of CFA followed by daily injections of ≥300 IU of hp-hMG from Day 8 of stimulation until the day of ovulation trigger (group B), in a fixed GnRH antagonist protocol.Results: LBRs after fresh embryo transfer (ET) were similar in group A 71/510 (14%) and B 42/407 (10%). Cumulative LBR per cycle was significantly higher in group A (16.9%) compared to group B (11.8%); (P = 0.03). However, logistic regression analysis showed no association between the type of gonadotropin administered and cumulative LBR. Only age was significantly associated with cumulative LBR (OR = 0.93, P = 0.007).Conclusion: Cumulative LBRs are similar in Bologna poor responders stimulated with CFA followed by hp-hMG compared to hp-hMG monotreatment in an antagonist protocol.

Several infertile patients, who may even represent around 40% of the infertile cohort, may respond “suboptimally” (4–9 oocytes retrieved) following IVF, despite being predicted as normal responders. The aim of our longitudinal study was to evaluate the ovarian response of suboptimal responders in terms of the number of oocytes retrieved, following their second IVF cycle, evaluating exclusively patients who had the same stimulation protocol and used the same or higher initial dose of the same type of gonadotropin compared to their previous failed IVF attempt. Overall, our analysis included 160 patients treated with a fixed antagonist protocol in their second cycle with the same [53 (33.1%)] or higher [107 (66.9%)] starting dose of rFSH. The number of oocytes retrieved was significantly higher in the second IVF cycle [6 (5–8) vs. 9 (6–12), p < 0.001]. According to our results, a dose increment of rFSH remained the only significant predictor of the number of oocytes retrieved in the subsequent IVF cycle (coefficient 0.02, p-value = 0.007) after conducting GEE multivariate regression, while adjusting for relevant confounders. A regression coefficient of 0.02 for the starting dose implies that an increase of 50 IU of the initial rFSH dose would lead to 1 more oocyte.