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Pineal cysts are benign, nonneoplastic lesions of the pineal gland, often identified incidentally on MRI scans. Although these cysts are usually asymptomatic, they can occasionally enlarge and compress adjacent structures, leading to neurological complications such as obstructive hydrocephalus and Parinaud's syndrome. The underlying mechanisms of pineal cyst development remain largely unclear, although inflammation - common in rheumatological conditions such as fibromyalgia - and mechanical stress have been suggested as contributing factors. In addition, the incomplete blood-brain barrier of the pineal gland raises the possibility that chronic lithium therapy, commonly used for psychiatric disorders and also known for its hyperplastic effects, could facilitate cysts formation through lithium accumulation and epithelial stimulation.We report the case of a 49-year-old woman with bipolar disorder on long-term lithium treatment who presented with a pineal cyst and clinical symptoms consistent with fibromyalgia. A review of the literature highlights possible links between pineal cyst formation, systemic inflammation associated with rheumatological disorders and prolonged lithium exposure.Although the hyperplastic properties of lithium in glandular tissue are well documented, there is no conclusive evidence directly linking lithium use to the development of pineal cysts in humans. The possibility of cystic growth driven by the pro-inflammatory environment of fibromyalgia remains plausible and warrants further investigation of the complex interactions between lithium therapy, systemic inflammation and pineal cystogenesis, particularly in patients with coexisting rheumatological and psychiatric disorders.

Background: Combining osteotomies and soft tissue procedures is believed to reduce sesamoids in their anatomical position and maintain long-term correction when treating hallux valgus deformity. This study determines if a radiologic association exists between a radiolucent sign and a full percutaneous adductor tendon release (PATR), including a cadaveric study and a consecutive case series. Another aim was to determine the intra- and interobserver reliability of these observations. Methods: A prospective observational study was made between 2018 and 2019. First, a PATR was done on cadaveric specimens and, after the procedures, dissected to correlate what was seen fluoroscopically. The clinical group included 39 feet that presented mild-to-moderate HV deformity and were treated with percutaneous osteotomies associated with PATR. Results: Observers 1 and 2 saw a radioscopic radiolucent sign in 100% of cadavers and the patient population. They also observed a triangle-shaped image with an incidence of 75%, which we have named the “triangle sign.” Conclusion: The triangle sign may be helpful in the intraoperative confirmation of PATR and latero-plantar capsule release using this percutaneous technique. Level of Evidence: Level II, development of diagnostic criteria.

Objective:. To evaluate the influence of enhanced recovery pathway (ERP) on patient-reported outcome measures (PROMs) and return to intended oncologic therapy (RIOT) after colorectal surgery. Background:. ERP improves early outcomes after colorectal surgery; however, little is known about its influence on PROMs and on RIOT. Methods:. Prospective multicenter enrollment of patients who underwent colorectal resection with anastomosis was performed, recording variables related to patient-, institution-, procedure-level data, adherence to the ERP, and outcomes. The primary endpoints were PROMs (administered before surgery, at discharge, and 6 to 8 weeks after surgery) and RIOT after surgery for malignancy, defined as the intended oncologic treatment according to national guidelines and disease stage, administered within 8 weeks from the index operation, evaluated through multivariate regression models. Results:. The study included 4529 patients, analyzed for PROMs, 1467 of which were analyzed for RIOT. Compared to their baseline preoperative values, all PROMs showed significant worsening at discharge and improvement at late evaluation. PROMs values at discharge and 6 to 8 weeks after surgery, adjusted through a generalized mixed regression model according to preoperative status and other variables, showed no association with ERP adherence rates. RIOT rates (overall 54.5%) were independently lower by aged > 69 years, ASA Class III, open surgery, and presence of major morbidity; conversely, they were independently higher after surgery performed in an institutional ERP center and by ERP adherence rates > median (69.2%). Conclusions:. Adherence to the ERP had no effect on PROMs, whereas it independently influenced RIOT rates after surgery for colorectal cancer.

Category: Bunion Introduction/Purpose: Percutaneous or minimally invasive surgery (MIS) forefoot surgery has experienced a vertiginous and sustained growth especially in the last decade. This is supported by numerous studies among which can be mentioned: clinical series, comparative studies, technique reports, radiological validations. Two cadaveric studies considered percutaneous forefoot surgery safe and has reported minimal risk which is consistent with clinical studies. We can consider that MIS forefoot surgery is transiting a sustained and responsible experience based on Third generation (TG) techniques (Open Chevron like). The purpose of this cadaveric study was to investigate the risk of iatrogenic neurovascular and tendon injury in a TG technique. Particularly, this study evaluated the Percutaneous, Intraarticular, Chevron Osteotomy (PICO) for the correction of hallux valgus. Methods: Eight unpaired feet, from Caucasian fresh frozen voluntary donor specimens were carefully dissected. One surgeon (JJDV) performed all of the procedures. In each foot, the surgeon performed a PICO and a lateral release of the first metatarsophalangeal joint (MTPJ). To evaluate the safety of the procedure the following data was obtained: 1. Distance between (DB) PICO portal (PP) and lateral border of the extensor hallucis longus (EHLT); 2. DB PP and dorsomedial digital nerve (DMDN); 3. DB PP and MTPJ; 4. DB Osteosynthesis portal (OP) and MTPJ; 5. DB OP and lateral border of EHLT; 6. DB OP and DMDN. This anatomical study also assessed if any arterial plexus damage was present via an indirect method by examination of the capsule and soft tissue around the first metatarsal. In addition, the following measurements were taken: angulation of osteotomy in the sagittal plane (Reproducibility) and IMA and HV angles (Correction power). Results: Two independent observers made all the assessments. The results of the safety measurements were as follow: 1. Average: 17,64 (range: 12,72-21,31); 2. Average: 7,29 (range:1,62-10,41); 3. Average: 15,72 (range: 9,48-20,52); 4. Average: 25,55 (range: 22,06-30,44); 5. Average: 12,77 (range: 8,04-16,71); 6. Average: 4,14 (range:1,72-8,20). There were no iatrogenic injuries. Nevertheless, the DB OP and DMDN showed the lowest average distance. With respect of the osteotomy angulation in the sagittal plane (Reproducibility), the average was: 85,62º (range: 78-100). Mean preoperative intermetatarsal angle (IMA) was 9,75° (range: 8-18°), and postoperatively the mean IMA was 8° (range: 4-13°). Before surgery the mean hallux valgus angle (HVA) was 22° (range: 13-40°) and the average postoperative HVA was 13,5° (range: 6-34°). Conclusion: The “Third generation” (TG) techniques reliably mimics the open Chevron procedure with all its known virtues whilst does not reproduce its disadvantages and complications. Also, according to several studies, these surgeries are useful, effective and (maybe) easier than open procedures. The proposed surgery (PICO) has shown to be safe, reproducible and have effective correction power when performed by a single surgeon (Trained in MIS surgery). We emphasize that percutaneous surgery has an extensive learning curve and therefore it may be difficult to reproduce the results initially.

Category: Midfoot/Forefoot Introduction/Purpose: Bunionette refers to painful lateral prominence at the fifth metatarsal head. For refractory cases, surgical intervention is indicated. Several operative treatments have been used to treat this deformity. Open surgery has been associated with wound healing problems, symptomatic hardware and infection. Recently, there has been a growing interest in the u utilization of minimally invasive surgery (MIS) essentially because of its inherent advantages, including less surgical trauma and preservation of blood supply. This has a direct impact in the patient leading to lower morbidity rates and faster recovery with immediate weight bearing. The purpose of the study was to describe both clinical and radiographic medium-term results of a sliding distal metatarsal minimally invasive osteotomy (S-DMMO) for correction of bunionette deformity. Methods: This is a retrospective review of patients who underwent S-DMMO to treat symptomatic bunionette deformity. We studied 46 feet from 36 patients, who were treated between Feb 2012 and March 2016. The surgeries were performed by two surgeons trained in minimally invasive surgery or percutaneous. The average follow-up was 49,74 years (33-70). The average age was 48 years (25-76). Radiographic measurements and clinical assessment were obtained preoperatively, six weeks postoperatively, and at final follow-up. Radiographic assessment includes evaluation of the fifth metatarsophalangeal angle, 4-5 intermetatarsal angles and medial osteotomy displacement (mm). Clinical evaluation included the lesser toe American Orthopaedic Foot and Ankle Society (AOFAS) score. The subjective satisfaction rate was measured using the Coughlin Score. Results: The mean 4-5 intermetatarsal angles was reduced from 10,88° to 7,1° and the fifth metatarsophalangeal angle was reduced from 14,7° to 6,47° postoperatively. Functional and clinical outcome, as assessed by a postoperative lesser toe AOFAS score showed good and excellent results (80-100 points) in all feet. The mean AOFAS score improved from 62,81pre-operatively to 92,42 points at final follow-up. Consolidation of the osteotomy site was achieved in all cases with a periosteal callus. According to the Coughlin classification system patient’s subjective assessments were: excellent (32 feet), good (12 feet) and fair (2 feet). No mayor complications were seen. One patient required reoperation (resection of symptomatic residual fifth metatarsal). Other complications found were: 1 superficial infection and 1 wound dehiscence. Conclusion: Our results showed that S-DMMO to be a safe and reliable technique for surgeons trained in MIS surgery. The mentioned is a novel, extrarticular and epiphasary technique that doesn´t need to be stabilized with osteosynthesis and provides a definite advantage over other techniques described. It is necessary to emphasize the importance of prevention of complications by a careful preoperative planning, a correct surgical procedure (specific instruments are required) and a strict postoperative control.

What Is This Summary About?: In this article, we summarize results from the ongoing phase 3 CheckMate 76K clinical study published online in Nature Medicine in October 2023. The study goal was to learn whether nivolumab works as an adjuvant therapy (that is, helps to keep cancer from coming back when it is given after surgery) for stage 2 melanoma (skin cancer) that has not spread to other parts of the body. Nivolumab is an immunotherapy that activates a person's immune system so it can destroy cancer cells. In melanoma, staging describes the severity of the cancer. Melanoma staging ranges from 0 (very thin and confined to the upper layer of the skin) to 4 (spread to distant parts of the body), with earlier stages removed by surgery. The people in this study had stage 2 melanoma that had not spread to the lymph nodes or other organs in the body., How Was the Study Designed?: People 12 years and older with stage 2 melanoma that had not spread and had been removed by surgery were included in CheckMate 76K. People were randomly assigned to receive either nivolumab (526 patients) or placebo (264 patients). A placebo resembles the test medicine but does not contain any active medicines. The researchers assessed whether people who received nivolumab lived longer without their cancer returning and/or spreading to other parts of their bodies (compared with placebo) and if nivolumab was well tolerated., What Were the Results?: Researchers found that people who received nivolumab were 58% less likely to have their cancer return and 53% less likely of having their cancer spread to distant parts of their body, compared with placebo. These reductions in risk with nivolumab were seen in different subgroups of people with a range of characteristics, and regardless of how deep the melanoma had gone into the skin. People taking nivolumab had more side effects than those taking placebo, but most were mild to moderate and manageable., What Do the Results Mean?: Results from CheckMate 76K support the benefit of using nivolumab as a treatment option for people with stage 2 melanoma post-surgery.

We provide evidence of geographical variations in the use of private health insurance (PHI) in Italy. Our study offers an original contribution, using a 2016 dataset on the use of PHI amongst a population of more than 200,000 employees of a major company. The average claim per enrolee was €925, representing approximately 50% of public health expenditure per capita, primarily for dental care (27.2%), specialist outpatient services (26.3%) and inpatient care (25.2%). Residents in northern regions and metropolitan areas respectively claimed reimbursements for €164 and €483 more than those in southern regions and in non-metropolitan areas. Both supply and demand factors can explain these large geographical differences. The study suggests the urgency for policymakers to address the considerable disparities in the Italian healthcare system, revealing the overall social, cultural and economic conditions that shape the demand for healthcare., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Since the second-half of the twentieth century, intracranial electroencephalography (iEEG), including both electrocorticography (ECoG) and stereo-electroencephalography (sEEG), has provided an intimate view into the human brain. At the interface between fundamental research and the clinic, iEEG provides both high temporal resolution and high spatial specificity but comes with constraints, such as the individual's tailored sparsity of electrode sampling. Over the years, researchers in neuroscience developed their practices to make the most of the iEEG approach. Here we offer a critical review of iEEG research practices in a didactic framework for newcomers, as well addressing issues encountered by proficient researchers. The scope is threefold: (i) review common practices in iEEG research, (ii) suggest potential guidelines for working with iEEG data and answer frequently asked questions based on the most widespread practices, and (iii) based on current neurophysiological knowledge and methodologies, pave the way to good practice standards in iEEG research. The organization of this paper follows the steps of iEEG data processing. The first section contextualizes iEEG data collection. The second section focuses on localization of intracranial electrodes. The third section highlights the main pre-processing steps. The fourth section presents iEEG signal analysis methods. The fifth section discusses statistical approaches. The sixth section draws some unique perspectives on iEEG research. Finally, to ensure a consistent nomenclature throughout the manuscript and to align with other guidelines, e.g., Brain Imaging Data Structure (BIDS) and the OHBM Committee on Best Practices in Data Analysis and Sharing (COBIDAS), we provide a glossary to disambiguate terms related to iEEG research., (Copyright © 2022. Published by Elsevier Inc.)

Background: Outcomes of patients with metastatic melanoma discontinuing BRAF-targeted therapy for cumulative toxicity after sustained response are unknown., Materials and Methods: This retrospective case series analysis conducted at a single Cancer Center in Italy included patients with BRAF mutated metastatic melanoma treated with a BRAF inhibitor as a single agent or in combination with a MEK inhibitor between June 1, 2011 and January 1, 2020 and interrupted treatment due to cumulative toxicity after achieving complete response (CR) or long-lasting partial response (PR; i.e. >12 months)., Results: We included 24 patients with a median treatment duration of 59.4 months (95% confidence interval [CI], 55.4-63.4; range, 12-88). CR and PR were achieved in 71% and 29% of patients, respectively. At a median follow-up after treatment discontinuation of 37.8 months (95% CI, 33.7-41.9), the 12-month progression-free survival after discontinuation (dPFS) rate was 70.8% (95% CI 54.8-91.6) and 24-month dPFS rate was 58.3% (95% CI, 41.6-81.8). Baseline patient and tumor characteristics as well as treatment duration and best response did not significantly impact on dPFS. Patients with CR and negative circulating tumor DNA (ctDNA) at time of discontinuation had a significantly improved dPFS compared with patients with either radiological residual disease or ctDNA positivity (p = .007). No patient in CR with undetectable ctDNA experienced progression., Conclusion: The risk of progression is high even in patients with sustained sensitivity to BRAF/MEK inhibitors. Integration of liquid biopsy in clinical trials investigating the optimal management of patients with sustained sensitivity to BRAF/MEK inhibitors is warranted., Implications for Practice: Outcomes of patients with metastatic melanoma discontinuing BRAF-targeted therapy for cumulative toxicity are unknown. This study analyzed patients with sustained responses (median treatment duration 59.4 months). Twelve- and 24-month progression-free survival following discontinuation were 70.8% and 58.3%, respectively. Complete response and negative circulating tumor DNA at time of discontinuation are promising prognostic biomarkers in this setting., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

The objective of the present work was to identify electroencephalographic (EEG) components in order to distinguish between braking and accelerating intention in simulated car driving. To do so, we collected high-density EEG data from thirty participants while they were driving in a car simulator. The EEG was separated into independent components that were clustered across participants according to their scalp map topographies. For each component, time-frequency activity related to braking and acceleration events was determined through wavelet analysis, and the cortical generators were estimated through minimum norm source localisation. Comparisons of the time-frequency patterns of power and phase activations revealed that theta power synchronisation distinguishes braking from acceleration events 800 ms before the action and that phase-locked activity increases for braking 800 ms before foot movement in the theta-alpha frequency range. In addition, source reconstruction showed that the dorso-mesial part of the premotor cortex plays a key role in preparation of foot movement. Overall, the results illustrate that dorso-mesial premotor areas are involved in movement preparation while driving, and that low-frequency EEG rhythms could be exploited to predict drivers' intention to brake or accelerate., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAF V600 mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population., Patients and Methods: In this open-label, multicentre study, patients with previously treated or untreated melanoma and the BRAF V600 mutation received vemurafenib 960 mg twice daily. The primary endpoint was safety. In a post hoc analysis, overall survival (OS) was analysed according to a prognostic scoring system developed using Eastern Cooperative Oncology Group performance status, existence of brain metastases and baseline serum lactate dehydrogenase level. The index was validated using data from patients treated with vemurafenib or dacarbazine in three clinical trials and data from patients treated with vemurafenib plus cobimetinib in two studies. The study is registered with ClinicalTrials.gov (NCT01307397)., Results: Between March 2011 and January 2013, 3224 patients were enrolled, and 3219 patients received ≥1 dose of vemurafenib (safety population); median follow-up time was 33.4 months. Vemurafenib's long-term benefits were confirmed, and no new safety signals identified. The prognostic index showed between-group differences in OS, with tight, non-overlapping confidence intervals. Validation in a pooled group of 666 vemurafenib-treated clinical trial patients revealed a similar pattern; the pattern was similar in 280 patients treated with vemurafenib plus cobimetinib., Conclusions: Final results from the vemurafenib safety study confirm vemurafenib's tolerability in BRAF V600 mutation-positive patients and resemble those seen in real-world clinical practice. This index may be useful in patients on combination therapy and as a basis for further work., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this review article, yeast model-based research advances regarding the role of Amyloid-β (Aβ), Tau and frameshift Ubiquitin UBB +1 in Alzheimer’s disease (AD) are discussed. Despite having limitations with regard to intercellular and cognitive AD aspects, these models have clearly shown their added value as complementary models for the study of the molecular aspects of these proteins, including their interplay with AD-related cellular processes such as mitochondrial dysfunction and altered proteostasis. Moreover, these yeast models have also shown their importance in translational research, e.g., in compound screenings and for AD diagnostics development. In addition to well-established Saccharomyces cerevisiae models, new upcoming Schizosaccharomyces pombe , Candida glabrata and Kluyveromyces lactis yeast models for Aβ and Tau are briefly described. Finally, traditional and more innovative research methodologies, e.g., for studying protein oligomerization/aggregation, are highlighted.