Non-motor fluctuations (NMFs) in Parkinson’s disease (PD) significantly affect patients’ well-being. Despite being identified over two decades ago, NMFs remain largely underrecognized, undertreated, and poorly understood. While they are often temporally associated with motor fluctuations (MFs) and can share common risk factors and pathophysiologic mechanisms, NMFs and MFs are currently considered distinct entities. The prevalence and severity of NMFs, often categorized into neuropsychiatric, sensory, and autonomic subtypes, vary significantly across studies due to the heterogeneous PD populations screened and the diverse evaluation tools applied. The consistent negative impact of NMFs on PD patients’ quality of life underscores the importance of further investigations via focused and controlled studies, validated assessment instruments and novel digital technologies. High-quality research is essential to illuminate the complex pathophysiology and clinical nuances of NMFs, ultimately enhancing clinicians’ diagnostic and treatment options in routine clinical practice.

The RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.

Background: and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods: ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results: Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Endoscopic vacuum therapy (EVT) has emerged as a transformative approach for managing gastrointestinal (GI) transmural defects, offering a less invasive and more promising alternative to surgery. Initially developed to address anastomotic leaks after rectal surgery, the application of EVT has expanded to include other locations within the GI tract. This review investigated the principles, indications, procedures, outcomes, challenges, and future perspectives of EVT for the management of GI transmural defects. In conclusion, EVT has demonstrated favorable outcomes in GI defect closure, with reduced complications, shortened hospital stay, and decreased morbidity rates as compared with conventional treatments. Although EVT faces challenges in some specific anatomical locations and in managing severe complications such as major bleeding, ongoing advancements in technology and standardization efforts offer promise for broader indications and better outcomes. Future perspectives include exploring novel EVT devices, refining patient selection criteria and pre-emptive applications, and standardizing procedural protocols.

Laparoscopic total pancreatectomy (LTP) is technically challenging and infrequently documented in the literature. In this paper, we present a new approach for performing fully LTP, a pancreatic tail-first approach with a counterclockwise technique, to accomplish total mesopancreas dissection and standard lymphadenectomy en bloc. Firstly, the tail and body of the pancreas without the spleen were dissected retrogradely, starting from the lower border of the body of pancreas and then from left to right. After that, a counterclockwise dissection of the tail and body of the pancreas was performed. The splenic artery and vein were divided at the terminal end of the pancreatic tail. The spleen was preserved. The entire body and tail of the pancreas were then pulled to the right side. This maneuver facilitated the isolation and dissection of arteries in the retropancreatic region more easily via laparoscopy, including the splenic artery, gastroduodenal artery, and supporting superior mesenteric artery first-approach. It also enabled total mesopancreas dissection.The inferior pancreaticoduodenal artery was resected last during this phase. The remainder of the dissection was like that of a laparoscopic pancreaticoduodenectomy with total mesopancreas dissection, involving two laparoscopic manual anastomoses. The operative time was 490 minutes and the total blood loss was 100 mL. Pathology revealed a low-grade intraductal papillary mucinous neoplasm extending from the head to the tail of the pancreas.

Methods: This study included 41 patients with single-level grades 1 or 2 LS from February 2023 to February 2024. Clinical outcomes were assessed using the Visual Analog Scale (VAS) for back and leg pain and the Oswestry Disability Index (ODI). Bridwell fusion grades were evaluated via lumbar spine computed tomography performed 6 months postoperatively. Results: Over a mean follow-up period of 10.6 months (range, 7–18 months), significant improvements were observed in VAS scores for low back pain (from 7.8±0.8 to 2.1±1.4) and leg pain (from 8.1±1.3 to 1.9±1.5) as well as ODI scores (from 50.4±15.4 to 14.8±10.5). The cohort consisted of patients with grades 1 (73.2%) and 2 LS (26.8%) at L4–L5 (58.6%), L5–S1 (34.1%), and L3–L4 (7.3%) levels. The mean operation time was 182.8±36.4 minutes, with a mean intraoperative blood loss of 190.5±81.3 mL and a mean hospital stay of 7.2±3.6 days. Successful fusion (Bridwell grades I/II) was achieved in 82.9% of the cases, with a 4.9% incidence of cage subsidence. Minor complications included durotomies in two patients (4.9%), whereas no major complications, such as nerve root injury, hardware-related issues, or postoperative infections, were reported. Conclusions The described BE-LIF technique, using HA bone grafts, which are an autologous bone from the preserved IAP, and a TLIF cage, is a viable, safe, and effective option for treating low-grade LS. This approach achieves favorable clinical outcomes and high fusion rates, which provides a cost-effective alternative to advanced surgical implants.