Early treatment with rifaximin during epileptogenesis reverses gut alterations and reduces seizure duration in a mouse model of acquired epilepsy.

The gut microbiota is altered in epilepsy and is emerging as a potential target for new therapies. We studied the effects of rifaximin, a gastrointestinal tract-specific antibiotic, on seizures and neuropathology and on alterations in the gut and its microbiota in a mouse model of temporal lobe epilepsy (TLE). Epilepsy was induced by intra-amygdala kainate injection causing status epilepticus (SE) in C57Bl6 adult male mice. Sham mice were injected with vehicle. Two cohorts of SE mice were fed a rifaximin-supplemented diet for 21 days, starting either at 24 h post-SE (early disease stage) or at day 51 post-SE (chronic disease stage). Corresponding groups of SE mice (one each disease stage) were fed a standard (control) diet. Cortical ECoG recording was done at each disease stage (24/7) for 21 days in all SE mice to measure the number and duration of spontaneous seizures during either rifaximin treatment or control diet. Then, epileptic mice ± rifaximin and respective sham mice were sacrificed and brain, gut and feces collected. Biospecimens were used for: (i) quantitative histological analysis of the gut structural and cellular components; (ii) markers of gut inflammation and intestinal barrier integrity by RTqPCR; (iii) 16S rRNA metagenomics analysis in feces. Hippocampal neuronal cell loss was assessed in epileptic mice killed in the early disease phase. Rifaximin administered for 21 days post-SE (early disease stage) reduced seizure duration (p < 0.01) and prevented hilar mossy cells loss in the hippocampus compared to epileptic mice fed a control diet. Epileptic mice fed a control diet showed a reduction of both villus height and villus height/crypt depth ratio (p < 0.01) and a decreased number of goblet cells (p < 0.01) in the duodenum, as well as increased macrophage (Iba1)-immunostaining in the jejunum (p < 0.05), compared to respective sham mice. Rifaximin's effect on seizures was associated with a reversal of gut structural and cellular changes, except for goblet cells which remained reduced. Seizure duration in epileptic mice was negatively correlated with the number of mossy cells (p < 0.01) and with villus height/crypt depth ratio (p < 0.05). Rifaximin-treated epileptic mice also showed increased tight junctions (occludin and ZO-1, p < 0.01) and decreased TNF mRNA expression (p < 0.01) in the duodenum compared to epileptic mice fed a control diet. Rifaximin administered for 21 days in chronic epileptic mice (chronic disease stage) did not change the number or duration of seizures compared to epileptic mice fed a control diet. Chronic epileptic mice fed a control diet showed an increased crypt depth (p < 0.05) and reduced villus height/crypt depth ratio (p < 0.01) compared to respective sham mice. Rifaximin treatment did not affect these intestinal changes. At both disease stages, rifaximin modified α- and ß-diversity in epileptic and sham mice compared to respective mice fed a control diet. The microbiota composition in epileptic mice, as well as the effects of rifaximin at the phylum, family and genus levels, depended on the stage of the disease. During the early disease phase, the abundance of specific taxa was positively correlated with seizure duration in epileptic mice. In conclusion, gut-related alterations reflecting a dysfunctional state, occur during epilepsy development in a TLE mouse model. A short-term treatment with rifaximin during the early phase of the disease, reduced seizure duration and neuropathology, and reversed some intestinal changes, strengthening the therapeutic effects of gut-based therapies in epilepsy.

A randomized prospective comparative study on sinonasal morbidity and quality of life of transsphenoidal endoscopic surgery for pituitary adenomas: endonasal versus trans-septal approach.

PURPOSE: Endoscopic endonasal transsphenoidal approach (Endonasal approach) is commonly used to treat pituitary adenomas. The extent of dissection possibly changes the anatomy and the physiology of the nasal cavities and could give rise to post-operative morbidity and the quality of life (QoL). The purpose of this study was to investigate sinonasal morbidity and general QoL in patients who underwent surgery for treatment of pituitary adenoma, comparing Endonasal and endoscopic trans-septal transsphenoidal approach (Trans-septal approach). METHODS: A prospective observational study, recruiting 40 patients undergoing surgery for pituitary adenoma, 20 via Endonasal approach and 20 via Trans-septal approach at our institution. Surveys with Sinonasal Outcome Test-22 (SNOT-22), Chronic Sinusitis Survey (CSS), and Short Form Health Survey 36 version 2 (SF-36v2) were obtained to collect QoL data pre- and postoperatively. RESULTS: All the 40 patients completed the questionnaires. At 6 months postoperatively, the SNOT-22 and CSS score shows significant improvements both in Endonasal approach (p = 0.01) and in Trans-septal approach (p = 0.02). No significant difference in sinonasal morbidity is observed between the two groups for SNOT-22 (p = 0.13) and CSS scores, except for sinus headache (p = 0.49), with a better score in Endonasal approach. The mean SF-36v2 scores remain the same in pre- and post-operative periods, but an improvement in time is seen in general health (p = 0.027), and general health compared to one year ago (p < 0.001). CONCLUSIONS: Endoscopic transsphenoidal surgery has negligible morbidity and does not negatively affect the nasal function in the long term. Endonasal approach and Trans-septal approach are comparable in terms of morbidity outcomes and general QoL, leaving the choice of the approach to the surgeon preference.

Preoperative systemic inflammatory markers as prognostic factors in differentiated thyroid cancer: a systematic review and meta-analysis.

BACKGROUND: Inflammation has been associated with tumor development and circulating inflammatory biomarkers have been proposed as possible predictors of recurrence of several solid tumors. However, the role of inflammation markers in differentiated thyroid carcinoma (DTC) is still uncertain. OBJECTIVE: This meta-analysis aimed to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in patients with DTC. METHODS: Studies investigating the association between survival and preoperative circulating inflammatory markers in DTC patients were included. The primary outcome was disease-free survival (DFS). Cumulative logarithms of the hazard ratio (log-HRs) with 95% CI were calculated through the inverse variance method using a random-effects model. RESULTS: A total of 7599 patients with a mean age of 48.89 (95% CI 44.16-53.63) were included. The estimated pooled log-HRs for DFS were 0.07 for NLR (95% CI -0.12-0.26; p = 0.43), -0.58 for LMR (95% CI -1.21-0.05; p = 0.06), and 0.01 (95% CI 0-0.01; p = 0.21) for PLR. CONCLUSIONS: Our meta-analysis showed no association between NLR, PLR, LMR and DFS in DTC; however, more prospective data are needed to better define the association between inflammatory status and prognosis of DTC.

Psychiatric Burden in Chronic Sinonasal Diseases: A Single-Center Cross-Sectional Observational Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis (CRS) and nasal septum deviation (SD) are two widely diffused clinical conditions in otorhinolaryngology clinical practice. Albeit nasal symptoms are the most commonly referred by patients affected by both conditions, recent evidence has explored the impairment of nasal function beyond its local implication. Indeed, the prevalence of psychiatric disorders, specifically anxiety and depression, was found higher in patients suffering from SD or CRS than in the general population. The aim of this study was to evaluate the psychiatric burden of these conditions in terms of anxiety and depression and to assess its relationship with clinical phenotype and age. METHODS: Monocentric cross-sectional observational study. Consecutive patients affected by CRS with or without nasal polyps or by SD were considered eligible. At referral, each patient underwent nasal endoscopy for clinical diagnosis and had to fill in the Hospital Anxiety and Depression Scale (HADS), the Sinonasal Outcome Test-22 (SNOT-22), and the Visual Analogue Scale (VAS) for global nasal symptoms. The population was grouped according to disease and age. RESULTS: One hundred fifty patients were enrolled. We observed a statistically significant difference in mean HADS score between patients affected by CRS with nasal polyps and those suffering from CRS without nasal polyps or SD both in the overall population and by age groups. Nevertheless, there was no significant difference in the HADS score between younger patients affected by CRS and SD. The mean HADS score was significantly higher in younger patients affected by SD compared to older. Furthermore, we observed an inverse correlation between age and HADS score in each disease group, statistically significant for SD. On the contrary, in the overall population, HADS score and patient-related outcomes (PROs) were directly correlated.  Conclusions: In the era of personalized medicine, our work remarks on the critical impact of anxiety and depression on the quality of life (QoL) of patients affected by sinonasal conditions. According to our results, age affects patient-reported outcomes (PROs) and should, therefore, be enhanced in the therapeutic decision process.

Development of machine learning models to predict lymph node metastases in major salivary gland cancers.

INTRODUCTION: Indications for elective treatment of the neck in patients with major salivary gland cancers are still debated. Our purpose was to develop a machine learning (ML) model able to generate a predictive algorithm to identify lymph node metastases (LNM) in patients with major salivary gland cancer (SGC). METHODS: A Retrospective study was performed with data obtained from the Surveillance, Epidemiology, and End Results (SEER) program. Patients diagnosed with a major SGC between 1988 and 2019 were included. Two 2-class supervised ML decision models (random forest, RF; extreme gradient boosting, XGB) were used to predict the presence of LNM, implementing thirteen demographics and clinical variables collected from the SEER database. A permutation feature importance (PFI) score was computed using the testing dataset to identify the most important variables used in model prediction. RESULTS: A total of 10 350 patients (males: 52%; mean age: 59.9 ± 17.2 years) were included in the study. The RF and the XGB prediction models showed an overall accuracy of 0.68. Both models showed a high specificity (RF: 0.90; XGB: 0.83) and low sensitivity (RF: 0.27; XGB: 0.38) in identifying LNM. According, a high negative predictive value (RF: 0.70; XGB: 0.72) and a low positive predictive value (RF: 0.58; XGB: 0.56) were measured. T classification and tumor size were the most important features in the construction of the prediction algorithms. CONCLUSIONS: Classification performance of the ML algorithms showed high specificity and negative predictive value that allow to preoperatively identify patients with a lower risk of LNM. LAY SUMMARY: Based on data from the Surveillance, Epidemiology, and End Results (SEER) program, our study showed that machine learning algorithms owns a high specificity and negative predictive value, allowing to preoperatively identify patients with a lower risk of lymph node metastasis.

Sentinel lymph node biopsy in high-risk cutaneous squamous cell carcinoma of the head and neck: Systematic review and meta-analysis.

The aim of our study was to better define the role of sentinel lymph node biopsy (SLNB) in high-risk cutaneous squamous cell carcinoma of the head and neck (cSCCHN). A systematic review and meta-analysis was performed according to the PRISMA statement. Seven-hundred and five patients were included from 20 studies. The pooled SLN identification rate was 98.8% (95%CI: 97.0-99.8). The median number of SLN excised was 3.6 (n = 371, 95%CI: 2.0-4.4). The pooled SLNB positive rate and cumulative regional recurrence rate (RRR) in negative SLNB were 5.6% (95%CI: 2.6-9.6) and 2.9% (95%CI: 0.5-7.2), respectively. The high SLN identification rate demonstrates SLNB feasibility in cSCCHN. The low SLNB positive rate and the relatively high RRR raise some doubts concerning its clinical utility. Further studies are mandatory to define predictors of lymph node metastases able to better select patients that may benefit from a SLNB.