PD Rating Research Articles

Clinical progression of Parkinson’s disease in the early 21st century: Insights from the Accelerating Medicine Partnership (AMP-PD) data

BackgroundParkinson’s disease (PD) therapeutic strategies have evolved since levodopa introduction in mid 1900s. To understand their impact and research gaps, this study delineated the clinical progression of PD in recent years. MethodsUsing Accelerating Medicine Partnership-PD (AMP-PD) data harmonized from seven biomarker discovery studies (2010-2020), we extracted: overall [Schwab and England (S&E), PD Questionnaire (PDQ-39)]; motor [Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS)-II and -III and Hoehn & Yahr (HY)]; and non-motor [MDS-UPDRS-I, University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), and Epworth Sleepiness Scale (ESS)] scores. Age at diagnosis was set as 0 years, and data were tracked for 15 subsequent years. ResultsAmong 3,001 PD cases identified to be suitable for this study, 2,838 are white, 1,843 are males, with a mean age at diagnosis was 60.2±10.3 years. At baseline evaluation, the disease duration was 9.9±6.0 years overall, 1915 within 0-5, 541 with 6-10, 254 within 11-15, and 163 greater than 15 years. Participants largely reported independence (S&E, 5y: 86.6±12.3; 10y: 78.9±19.3; 15y: 78.5±17.0) and good quality of life (PDQ-39, 5y: 15.5±12.3; 10y: 22.1±15.8; 15y: 24.3±14.4). Motor scores displayed a linear progression, whereas non-motor scores plateaued ∼10-15 years. Younger onset age and female correlated with slower progression. ConclusionsTwenty-first century PD patients remain largely independent in the first decade of disease at tertiary subspecialty care and research centers. There are data gaps for those who are non-whites or longer PD duration, and sensible metrics that can gauge non-motor progression when PD is beyond 10 years.

A preoperative window-of-opportunity study of oral SERD, imlunestrant, in newly diagnosed ER-positive, HER2-negative early breast cancer: Results from EMBER-2 Study.

Imlunestrant is an oral SERD with favorable safety and preliminary efficacy in patients with ABC. PD biomarker data can optimize drug dosing; herein is the PD data from the EMBER-2 study. Postmenopausal women with untreated, operable ER-positive, HER2-negative EBC were randomized to 400mg vs 800mg of imlunestrant daily for ~2 weeks before surgery. A single arm testing 200mg daily was later accrued. PD biomarker changes (ER, PR, Ki-67 by IHC, and mRNA expression of ER-related genes) were evaluated in paired tumor samples (pre-/ post-treatment). Safety and PK were also assessed. Among evaluable paired samples (n=75), PD profiles demonstrated consistent ER targeting between 400 and 800mg doses with less toxicity at the 400mg dose. Although inducing the lowest rate of CCCA, PD and PK results were similar for the 200mg dose. EMBER-2 combined with existing phase 1 data has identified 400mg as the optimal imlunestrant dose.

Nontuberculous mycobacterial pulmonary disease (NTM PD) incidence trends in the United States, 2010–2019

BackgroundNontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that cause chronic lung disease. Rates of NTM pulmonary disease (NTM PD) have increased over the last several decades, yet national estimates in the United States (US) have not been assessed since 2015.MethodsWe used a nationally representative population of Medicare beneficiaries aged ≥ 65 years to assess rates of NTM PD in a high-risk population from 2010 to 2019. Poisson generalized linear models were used to assess the annual percent change in incidence in the overall population and among key demographic groups such as sex, geography, and race/ethnicity. We evaluated the relative prevalence of various comorbid conditions previously found to be associated with NTM PD.ResultsWe identified 59,724 cases of incident NTM PD from 2010 to 2019 from an annual mean population of 29,687,097 beneficiaries, with an average annual incidence of 20.1 per 100,000 population. NTM PD incidence was overall highest in the South and among women, Asian individuals, and persons aged ≥ 80 years relative to other studied demographic groups. The annual percent change in NTM PD incidence was highest in the Northeast, at 6.5%, and Midwest, at 5.9%, and among women, at 6.5%. Several comorbid conditions were highly associated with concurrent NTM diagnosis, including allergic bronchopulmonary aspergillosis, bronchiectasis, and cystic fibrosis.ConclusionsHere we provide current estimates of NTM PD incidence and prevalence and describe increasing trends in the US from 2010 to 2019. Our study suggests a need for improved healthcare planning to handle an increased future caseload, as well as improved diagnostics and therapeutics to better detect and treat NTM PD in populations aged ≥ 65 years.

Nitrogen-rich sulfur-containing heterocyclic adsorbents for effective selective adsorption of Au(III)/Pd(II)/Pt(IV)

Recovering precious metals from secondary resources has elicited considerable attention, and exploring an efficient adsorbent is a challenge. In this work, we have specifically tailored three highly effective adsorbents (THDA@PEI, DCTA@PEI and DCTD@PEI) by crosslinking PEI with sulfur-containing heterocyclic cross-linking agents (2,5-thiophenedicarboxaldehyde, 2,4-dichlorothiazole and 3,4-dichloro-1,2,5-thiadiazole) for recovery of Au(III), Pd(II), and Pt(IV). These agents are distinguished by a range of nitrogen atom counts that extend from zero to two, offering a foundation for exploring the correlation between their molecular structure and adsorption performance. THDA@PEI, DCTA@PEI, and DCTD@PEI exhibit remarkable adsorption capacities for Au(III), Pd(II), and Pt(IV), with values reaching up to 2169, 2240, and 2536 mg/g for Au(III), 771, 886, and 846 mg/g for Pd(II), and 832, 1021, and 887 mg/g for Pt(IV), respectively. Among the three materials, DCTD@PEI stands out with a broader pH applicability range for both gold (pH 2 to 9) and platinum (pH 1 to 11) adsorption and exhibits a more rapid adsorption rate for Au and Pd. The adsorption processes of the three adsorbents on precious metals are spontaneous and entropy-increasing processes. Increasing the adsorption temperature could improve the adsorption performance of the three adsorbents, except for Pd adsorption by DCTD@PEI. All of the three adsorbents exhibit good selectivity and reusability for Au, Pd, and Pt, with DCTA@PEI being the most outstanding. It is observed that an increase in nitrogen content in the adsorbents correlates positively with the improvement of key performance indicators, including a wider pH range, higher adsorption capacity, faster kinetics, better selectivity, and enhanced reusability, while the substituent positions of crosslinking agents also have a strong impact on the adsorption performance, especially for Pd and Pt.

Intracranial outcomes of 1L selpercatinib in advanced RET fusion-positive NSCLC: LIBRETTO-431 study.

199 Background: Selpercatinib is a highly selective and potent CNS active RET inhibitor approved for treatment of advanced RET fusion-positive ( RET+) NSCLC. Treatment or prevention of CNS disease is critical in RET+ NSCLC patients (pts), who have nearly a 50% lifetime prevalence of brain metastases (mets) (Drilon et al. JTO 2018). LIBRETTO-431 is the first study to compare intracranial (IC) efficacy of a targeted therapy to chemo/IO in pts with oncogene driven NSCLC. Methods: LIBRETTO-431 (NCT04194944) is a randomized, open-label, phase 3 trial comparing 1L selpercatinib vs chemotherapy (cisplatin/carboplatin + pemetrexed) +/- pembrolizumab. As previously reported, the study met its primary endpoint of PFS by blinded independent central review (BICR) at the pre-planned interim analysis. IC analyses included CNS and non-CNS PD, IC PFS and IC responses by BICR per RECIST 1.1 in all pts who had a baseline and one or more post-baseline CNS scans (CNS-evaluable) and were designated to receive pembrolizumab if randomized to the control arm (CNS-pembro population). Adverse events were evaluated in the CNS safety population. Results: A total of 192 of 261 pts enrolled were CNS-evaluable (selpercatinib: 120, control: 72). Baseline characteristics were generally balanced with the selpercatinib arm having a slightly lower proportion of pts with BICR-assessed baseline brain mets (21% vs 25%) and prior CNS radiotherapy (RT; 6% vs 10%) compared to the control arm. Selpercatinib delayed CNS PD as evidenced by a lower 12 mo cumulative incidence rate (CIR) for CNS PD, as well as delaying non-CNS PD compared to control in pts with and without brain mets (Table). In pts with measurable brain mets at baseline (n=29), median time to IC response per RECIST 1.1 was similar between selpercatinib and control (1.4 mo [range: 1.2-2.9] vs 1.6 mo [range: 1.2-2.9]); however, as previously reported the IC response rates were higher (82% vs 58%) and more durable (12 mo DOR rate 76% vs 63%) with selpercatinib vs control (Zhou et al. NEJM 2023). IC responses to selpercatinib were more common in pts without prior CNS RT (14/15, 93%) than with prior CNS RT (3/6, 50%). Conclusions: Selpercatinib delayed IC progression in advanced RET+ NSCLC pts with or without baseline brain mets and achieved higher IC response rates compared to chemotherapy + pembrolizumab. LIBRETTO-431 is the first study to demonstrate IC efficacy improvement of a targeted therapy vs chemo/IO in a biomarker selected NSCLC population. These data further support selpercatinib as the preferred 1L regimen in pts with advanced RET+ NSCLC. Clinical trial information: NCT04194944 . [Table: see text]

Analysis of mortality in Parkinson disease in China: Exploration of recent and future trends

AbstractObjectivesParkinson disease (PD) is the third leading cause of mortality among middle‐aged and older individuals in China. This study aimed to explore the trends and distribution features of PD mortality in China from 2013 to 2021 and make predictions for the next few decades.MethodsRelevant data were obtained from the Chinese Center for Disease Control and Prevention Disease Surveillance Point system. The joinpoint regression model was used to evaluate trends. The R software was used to predict future trends.ResultsAge‐standardized mortality rate (ASMR) of PD increased from 0.59 per 100,000 individuals to 1.22 per 100,000 individuals from 2013 to 2021, with an average annual percent change (AAPC) of 9.50 (95% CI: 8.24–10.78). The all‐age ASMR of PD were higher in male individuals than in female individuals, and ASMR increased with age. The number of deaths and ASMR increased gradually from west to east and from rural to urban areas. Furthermore, ASMR is expected to increase to 2.66 per 100,000 individuals by 2040.ConclusionsThe heightened focus on the ASMR of PD among male individuals, urban areas, eastern China, and individuals aged ≥85 years has become a key determinant in further decreasing mortality, thereby exhibiting novel challenges to effective strategies for disease prevention and control.

Effective Transport Recovery of Palladium(II) from Hydrochloric Acid Solutions Using Polymer Inclusion Membrane with Tetrabutylammonium Bromide.

This article reports on the extraction of palladium(II) from hydrochloric acid (HCl) solutions using polymer inclusion membranes (PIMs) containing tetrabutylammonium bromide (TBAB) as the ion carrier. The membranes were based on cellulose triacetate (CTA) as the polymer support. The main aim of this study is to determine the possibility of TBAB's application as the effective ion carrier/extractant of Pd(II) from hydrochloric acid solutions. At first, the effect of the hydrochloric acid concentration in the aqueous phase on palladium(II) extraction was investigated. Next, cellulose triacetate membranes with TBAB as the carrier were prepared and applied for the recovery of Pd(II) from HCl solutions. As a result of the investigations, the optimal composition of the receiving phase was determined to be 0.5 M thiourea in 0.1 M hydrochloric acid. The effect of the acid concentration in the source phase was investigated. The results show a linear decrease in the permeability coefficient and initial flux of palladium(II) with an increase in the hydrochloric acid concentration in the source phase. The separation of Pd(II) from Pt(IV) from the hydrochloric acid solution was also studied. The transport rate of Pd(II) was higher than Pt(IV). The separation coefficient SPd/Pt was 1.3. The results show that transport through PIMs with TBAB can be used as an effective method to recover Pd(II) from hydrochloric acid, especially at a low concentration of this acid.

#1125 CAPD in ESRD and CLD patients with refractory ascites: a 12-month follow-up study

Abstract Background and Aims Refractory ascites secondary to chronic liver disease among ESRD patients are a major source of morbidity and mortality. Hemodialysis is frequently interrupted due to intradialytic hypotension and other complications which make ultrafiltration removal among CLD patients, a big challenge. This results in sub-optimal clearance which translates into poor quality of life along with recurrent admissions. CAPD in these patients is effective in providing a good clearance as well as removal of ascites with adequate ultrafiltration removal. There is a lack of data regarding the feasibility, safety, and clinical outcomes of CAPD among CLD patients with ascites. We conducted a study with objectives to evaluate serum albumin levels at baseline and 12 months, and to determine peritonitis rates and dialysis modality suitability in CLD patients. Method Study Design A retrospective cohort study. Study Population All hemodialysis patients with refractory ascites due to CLD. Refractory ascites was defined as the need for >5 therapeutic paracentesis in the last 3 months after optimal clinical, dietary and fluid management. All CLD patients were extensively counselled regarding high protein intake. Each patient visited either the Nephrologist or PD Nurse, renal dietician at least once in 4-6 weeks. Results Over a period of five years, 34 patients were included in the analysis to assess the efficacy of Continuous Ambulatory Peritoneal Dialysis (CAPD) for ascites management in chronic liver disease. Baseline characteristics are presented in Table 1. The frequency of ascites drainage prior to CAPD was every 3.4 weeks. Open catheter insertion was performed in 31 out of 34 patients. Serum albumin levels increased from 2.98 ± 0.4 g/dL at baseline to 3.1 ± 0.28 g/dL at 12 months (p = 0.21) (Fig. 1). Child-Pugh Score and MELD score remained stable. Bacterial peritonitis episodes were higher at 12 months (3 vs 9; p = 0.04). PD-related complications at one year included one omental wrap, three pericatheter leaks, and one umbilical hernia. At the 12-month follow-up, 32 patients survived. One patient died from myocardial infarction, and another experienced severe hepatic encephalopathy and aspiration pneumonia. Conclusion PD was well tolerated in patients with refractory ascites, presenting no additional hypoalbuminemia risk. Continuous multidisciplinary monitoring for malnutrition remains critical. Peritonitis risk was elevated relative to SBP in HD patients yet was on par with typical PD rates, without an increase in hospital admissions.

Analysis of the correlation between peri-implant probing depth and radiographic bone level

Objective: To evaluate the correlation between peri-implant probing depth (PPD) and radiographic bone level (rBL) in implants with peri-implantitis. Methods: From January 2019 to December 2022, 24 patients with 30 implants who suffered from peri-implantitis at the Department of Periodontology, Peking University School and Hospital of Stomatology were included in the present research. SPSS 26.0 software was used to simple random sampling select 30 healthy implants from which with electronic examination records in Department of Periodontology, Peking University School and Hospital of Stomatology from January 2007 to June 2023 as the control group. On the premise of retaining the implant prosthesis, PPD (distance between pocket bottom and peri-implant soft tissue margin) was examined using a Williams periodontal probe with a light force (about 0.2 N), and a total of 4 sites were recorded for each implant. Periapical radiography and cone beam CT were applied to measure the rBL (distance between the reference point at the neck of the implant and the apical point of the bone defect) and the width of the bone defect (DW), and the type of the bone defect was recorded. The correlation and consistency between the diagnosis of PPD and rBL were analyzed. Results: PPD was significantly correlated with rBL in a total of 60 implants in 180 sites (r=0.64, P<0.001). The chi-square test showed an 8.15-fold increase in the detection rate of PD≥6 mm at sites with rBL≥1 mm (P<0.001). Multivariate logistic regression analysis showed that rBL was still statistically associated with PPD after adjustment for jaw position and examination position of implants. Take rBL <1 mm as reference, the odds ratios (OR) of 1 mm≤rBL<2 mm, 2 mm≤rBL<3 mm and rBL≥3 mm group with PPD were 6.23 (P=0.014), 2.77 (P=0.183) and 10.87 (P=0.001), respectively. Conclusions: There is a positive correlation between PPD and rBL in implants with peri-implantitis. PPD can be used as a clinical examination index to assist in estimating the level of peri-implant bone under the premise of retaining the prosthesis.

Efficacy and Safety of Cell-based Immunotherapy in The Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma – A Systematic Review and Meta-analysis

BackgroundRecurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective. MethodsWe systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias. ResultsWe screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %–29 %), median PFS of 2.37 months (95 %CI = 1.23–3.51) and median OS of 10.16 months (95 %CI = 0.67–19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %–93 %), SD rate was 22 % (95 %CI = 2 %–75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %–98 %), SD rate of 11 % (95 % CI = 0 %–82 %) and incidence rate of any grade adverse events of 29 % was achieved. ConclusionCBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.

Leaching of palladium from spent Pd/Al2O3 catalysts by coupled ultrasound-microwave technique

The recycling and reuse of spent Pd/Al2O3 catalysts have tremendous social, environmental, and economic benefits. Calcined-ClO2 and NH4Cl aqueous leaching method was investigated to recover Pd from spent Pd/Al2O3 catalysts, and ultrasound-microwave was introduced to intensify the leaching process, after which the surface morphology, valence, and content of major elements, and crystalline shape of carriers of the spent Pd/Al2O3 catalysts before and after the leaching were determined and analyzed. The results showed that ultrasonic-microwave-enhancement increased the leaching rate and shortened the leaching time of Pd in comparison with the conventional leaching experiments, and the leaching rate of Pd at 10 min of ultrasonic-microwave-enhanced leaching was 31.1 %, which was 13.6 % higher than that of the conventional conditions. The optimal process conditions: calcination temperature was 200 °C, calcination time was 90 min, the dosage of ClO2 was 15 % (V/Vall), the concentration of NH4Cl was 2 mol/L, the dosage of HCl (1 mol/L) was 15 % (V/Vall), the leaching power was 400 W, leaching temperature was 90 °C, leaching time was 60 min, and the liquid–solid ratio was 10:1. Eventually, the leaching rate of palladium was 80.6 %, and the average retention rate of carrier was about 94 %.

Can Dance Improve Turning in People With Parkinson's Disease?

Objective: To investigate the effects of a dance intervention on selected functional parameters during the 180° turning phase of the Timed Up & Go (TUG) test in people with Parkinson's Disease (PwPD). Methods: Fifteen adults clinically diagnosed with idiopathic PD were allocated into dance intervention (DIG; n = 7 ; age 73 ± 2 years) and control (CG; n = 8; age 64 ± 5 years) groups. The dance intervention lasted for 3 months (1 hour, twice a week). At baseline, all participants completed the Unified PD Rating Scale-part III, the International Physical Activity Questionnaire-short form, and the Hoehn & Yahr scale. Pre- and post-intervention, the primary outcomes were measured (number of steps and time to complete the 180° turning phase of the TUG test) at 2 speeds (comfortable walking and as quickly and safely speed) while using the Xsens® 3D motion suit. The secondary outcome (girdle dissociation) was assessed by calculating the difference between pelvis and affected shoulder orientation in the transverse plane (dissociation angles) at each data point during the TUG test's 180° turning phase. Results: At participant's comfortable walking speed, the functionality during the 180° turning remained unaffected following the dance intervention. However, at participant's fast speed, the dance intervention group significantly reduced the number of steps with a large effect size, and the total time taken to complete the 180° turning with a medium effect size. Post-intervention, most participants in the dance intervention group reduced the affected shoulder and pelvic girdle dissociation and turned more "en bloc." Conclusion: Dance can improve selected functional parameters during the 180° turning at fast speed in PwPD. The current results should be considered in rehabilitation programs.

Efficacy analysis of hepatic arterial infusion chemotherapy combined with targeted and immune therapy followed by 125I seeds implantation in the treatment of hepatocellular carcinoma with portal vain tumor thrombus

Objective: To investigate the safety and efficacy of Hepatic Arterial Infusion Chemotherapy(HAIC) combined with targeted and immune therapy followed by 125I seeds implantation in portal vain tumor thrombus (PVTT) in the treatment of hepatocellular carcinoma(HCC) with PVTT. Methods: A retrospective study was performed on the clinical data of 21 patients [ (11 men, 10 women) aged 34-73 (52.6±13.7) years] with HCC with PVTT in The First Affiliated Hospital of Zhengzhou University from October 2020 to October 2022, all of them were treated with HAIC plus targeted and immune therapy,and 125I seeds implanted into PVTT. The patients were followed up to January 2023, the efficacy was evaluated according to the modified version of the solid tumor efficacy evaluation criteria (mRECIST). The progression-free survival (PFS) rate, overall survival(OS) rate and portal tumor thrombus control rate at 3, 6, 12 and 18 months after treatment were recorded, and PFS and OS time were followed up. The changes of liver function, AFP, coagulation function and adverse events were observed. Results: Each patient received 2 to 7 (mean: 3.3±1.2) cycles of HAIC. 10-37 seeds (mean:16.6±6.7) were implanted per patients. The median follow-up time was 15 (range from 5 to 25) months.During the follow-up time, 15 patients showed progression and 6 patients died, and the PFS rates at 3, 6, 12, and 18 months after treatment were 90.5%, 71.4%, 42.9%, and 23.8%, respectively, and at 3, 6, 12, and 18-month OS rates were 100%, 100%, 81.0%, and 61.9%, respectively.The PVTT control rates at 3, 6, and 12 months were 90.5%, 90.5%, and 62.5%, respectively. Overall efficacy evaluation of CR rate 0, PR rate 47.6% (10/21), SD rate 38.1% (8/21), and PD rate 14.3% (3/21). The total incidence of treatment-related adverse events was 100%.Grade 3 treatment related adverse events were observed for 4 cases, the rest wereⅠtoⅡadverse events. Right upper abdominal pain, fever and hemorrhage in liver capsule related to the procedures were observed in 11(52.4%), 5(23.8%) and 3(14.3) patients, respectively. Conclusion: HAIC combined with targeted and immune therapy followed by 125I seeds implantation in PVTT is a safe and efficacy therapy for HCC with PVTT.

Molecular predictors of response to first-line systemic therapies in advanced hepatocellular carcinoma.

534 Background: With numerous advances in systemic therapy for advanced hepatocellular carcinoma (HCC) over the past several years, there are now multiple first-line treatment options which can be considered. These options include combination atezolizumab with bevacizumab (atezo/bev), programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) targeted agents, and oral multikinase inhibitor monotherapy. However, further guidance is needed to predict which patients will respond to best to each regimen. Methods: We performed a single center, retrospective study to determine the association between responses to first-line therapies in advanced HCC and various molecular alterations. Patients received first-line therapy with either atezo/bev, PD-1/PD-L1 monotherapy, or oral multikinase inhibitor monotherapy with treatment responses determined by imaging. All patients underwent next-generation sequencing (NGS) with testing performed on peripheral blood or tumor tissue. Results: A total of 116 patients with advanced HCC were included in this study. For first-line therapies, 45 (38.8%) patients received atezo/bev, 41 (35.3%) received oral multikinase inhibitor monotherapy, and 30 (25.9%) received PD-1/PD-L1 monotherapy. There was no association between treatment responses and patient ethnicity, age, or underlying cirrhosis etiology for any regimen. However, when analyzing NGS results, atezo/bev recipients with telomerase reverse transcriptase (TERT) promoter alterations had significantly higher rates of disease progression (PD) compared those without TERT promoter alterations (91.7% vs 54.6%, p = 0.03). In addition, in the oral multikinase inhibitor monotherapy group, those with CTNNB1 alterations had significantly greater PD rates compared to patients without these alterations (66.7% vs 31%, p = 0.04). There were no significant correlations between molecular alterations and responses in the PD-1/PD-L1 monotherapy group (Table). Conclusions: In our study, advanced HCC patients who received first-line systemic therapies were found to have significant correlations between TERT promoter and CTNNB1 alterations and responses to atezo/bev and oral multikinase inhibitor monotherapy, respectively. Given the widespread use of these regimens in the HCC treatment paradigm, additional studies are needed to confirm these findings and determine their impact on survival outcomes.[Table: see text]

Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors for muscle invasive bladder cancer: a systematic review and meta-analysis.

This meta-analysis aims to evaluate the efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors [PD-(L)1 inhibitors] for muscle-invasive bladder carcinoma (MIBC). Four databases (Medline, Embase, Web of Science, and 21 CENTRAL) were searched for articles studying neoadjuvant PD-(L)1 inhibitors for MIBC. The search time period was from the establishment of each database to 21 July 2023. Meta-analyses of pCR, pPR, Grade≥ 3 irAEs rate, RFS, and OS were performed. In total, 22 studies were included for meta-analysis. The overall pooled pCR of neoadjuvant PD-(L)1 inhibitors was 0.36 (95%CI=0.30-0.42, p=0.00). In subgroup meta-analysis, the pooled PCR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.27 (95%CI=0.19-0.35, p=0.1), 0.41 (95%CI=0.21-0.62, p=0.01), 0.43 (95%CI=0.35-0.50, p=0.06), respectively. The overall pooled pPR of neoadjuvant PD-(L)1 inhibitors was 0.53 (95%CI=0.46-0.60, p=0.00). In subgroup meta-analysis, the pooled pPR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.36 (95%CI=0.22-0.51, p=0.01), 0.51 (95%CI=0.39-0.62, p=0.43), and 0.61 (95%CI=0.53-0.69, p=0.01), respectively. Kaplan-Meier curves for OS and RFS were reconstructed, but there was no significant difference among three groups in terms of OS or RFS. The pooled result of Grade≥ 3 irAEs rate for neoadjuvant PD-(L)1 inhibitors was 0.15 (95%CI=0.09-0.22, p=0.00%). In subgroup analysis, the pooled result of Grade≥ 3 irAEs rate for PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.07 (95%CI=0.04-0.11, p=0.84), 0.31 (95%CI=0.16-0.47, p=0.06), and 0.17 (95%CI=0.06-0.31, I2 = 71.27%, p=0.01), respectively. Neoadjuvant PD-(L)1 inhibitors were feasible and safe for muscle invasive bladder cancer. Compared with PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI and PD-(L)1 inhibitors plus chemotherapy were associated with higher pCR and pPR, but higher Grade≥3 irAEs. Kaplan-Meier curves for OS and RFS indicated that neoadjuvant PD-(L)1 inhibitors had an acceptable long-term prognostic, but it was not possible to discern statistical differences between the three neoadjuvant subgroups. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023452437, identifier PROSPERO (CRD42023452437).

Magnetization and self-sharpening mechanism of polymerized diamond abrasive based on magnetorheological polishing technology

In magnetorheological polishing (MRP), the abrasive grains are confined in a semi-fixed mode by the chain strings formed by the magnetorheological particles to achieve the polishing of workpiece surfaces. The force of the abrasive particles on the workpiece comes from the force of the magnetic chain strings acting on the abrasives. However, the angular surface of the abrasive is generally smooth, resulting in a limited holding force on the abrasive by the magnetic chain strings. Therefore, the polishing force of the abrasives on the workpiece is small, and it is easy to slip and escape from the polishing area. In this paper, the sintering method is used to prepare polymerized diamond abrasive(PD) with microstructures on the surface, to increase the surface area of the abrasive and to improve the control force of the magnetic chain string on the abrasive. The prepared PD has a particle size of about 25.7 μm, with a rough surface and a large amount of 3 μm single-crystal diamond particles exposed. The MRP results show that the PD have more surface micro-cutting edges and stronger machinability than the commonly used single-crystal diamond abrasives(SCD). The material removal rate(MRR) of PD on silicon wafers and sapphire wafers was increased by 173.3 % and 122.2 %, respectively. The morphological changes of the PD were traced by scanning electron microscope(SEM), and it was found that: when polishing low-hardness materials, the wear of the PD was in the form of ceramic bond wear and diamond grit dislodgement; and when polishing high-hardness materials, the wear of the PD was in the form of ceramic bond breakage and PD fragmentation. When abrasive grit dislodgment occurs on the surface of the PD, the formed hole enhances the force between the PD and the magnetic chain strings. Which further enhances the holding force of the magnetic chain string on the PD, and can effectively improve the magnetorheological polishing efficiency.

Association between motor symptoms of Parkinson’s disease and swallowing disorders

BackgroundParkinson’s disease (PD) presents with motor symptoms that hinder physical activity. This study aimed to thoroughly investigate swallowing dysfunction in patients with PD using videofluoroscopy (VF) and the Movement Disorder Society (MDS)-Unified PD Rating Scale (UPDRS) sub-scores.MethodsThis study was part of an intervention project to evaluate the effectiveness of cervical percutaneous interferential current stimulation in patients with Hoehn and Yahr stages 2–4 PD. Baseline data, including swallowing-related indicators such as VF, were obtained and compared to the MDS-UPDRS sub-scores including rigidity, tremor, postural instability/gait difficulty, and limb scores.ResultsTwenty-seven patients were included in this study. In the VF analysis, laryngeal penetration/aspiration, oral cavity residue, epiglottic vallecular residue, and pharyngeal residue were observed with remarkable frequency. The multivariate analysis revealed that the mean rigidity score of UPDRS was an independent and significantly correlated factor with laryngeal penetration/aspiration during the ingestion of 10 mL of water (odds ratio 1.294, 95% confidence interval 1.035–1.617; p = 0.024).ConclusionThis study revealed a correlation between muscle rigidity and laryngeal penetration or aspiration risk. The detailed comparative analysis of various individual PD symptoms and swallowing disorders was substantial, which enabled early detection of the risk of swallowing disorder and the implementation of appropriate measures.Trial registration numberjRCTs062220013.

HPB P30 The role of interventional radiology in managing post-pancreatectomy hemorrhage at a major hepatobiliary centre in the UK

Abstract Background Pancreatoduodenectomy (PD) is a common surgery performed by hepatobiliary surgeons. Mortality is 5% and morbidity is 30-40%. An important cause is post-pancreatectomy hemorrhage (PPH). As per the International Study Group for Pancreatic Surgery (ISGPS), grade C PPH represents most cases of hemorrhage post-PD and always requires intervention. They tend to be arterial in origin and CT angiogram of the celiac axis and superior mesenteric artery is recommended. Historically, the treatment for PPH was a re-look laparotomy. With the development of interventional radiology (IR) techniques, morbidity and mortality has improved. Transcatheter arterial embolization is a well-established treatment for bleeding. Methods Southampton General Hospital is a tertiary centre for hepatobiliary surgery and interventional radiology. All patients who underwent PD between 2019 and 2023 were checked for complications. Patients who developed PPH were selected and their PACs was checked for what investigation they underwent. The findings of the angiogram and intervention done were recorded. Morbidity and mortality data was also collected including whether patients returned to theatre. Results Seven male patients aged 57 to 75 had type C PPH. Symptom onset including melaena and haematemesis was between 24 hours to 38 days. The time to CT from the request was between one to six hours. One patient was bleeding from the gastroduodenal artery stump. The other six patients had no obvious bleeding point identified. Of the seven patients, five had bleeding points identified on angiograms done by IR and underwent embolization. One patient returned-to-theatre for a re-look laparotomy. Two of seven patients died within one year of PPH. One had repeated PPH and had embolization multiple times. Conclusions Harnoss et al., (2014) reported that the rate of PPH post PD was 5.9%. The use of angiography with embolization is being adopted worldwide for arterial bleeding in hemodynamically stable patients due to its minimal invasiveness. Even if embolization fails, angiography can help identify the bleeding point and guide surgical management. The reported immediate mortality rate from PPH is 30% and at our centre it was 0% in our small sample size.

A novel hydrangea-like magnetic composite Fe3O4@MnO2@ZIF-67 for efficient selective adsorption of Pd(II) from metallurgical wastewater

The selective adsorption of palladium from wastewater is a feasible solution to solving palladium pollution and resource scarcity. Because traditional solvent extraction methods often involve the use of considerable amounts of organic solvents, research is focused on investigating adsorption techniques that can selectively remove palladium from wastewater. In this paper, the magnetic composite Fe3O4@MnO2@ZIF-67 was synthesized and its performance for the adsorption of Pd(II) in acidic water was investigated. Fe3O4@MnO2@ZIF-67 was characterized by various analytical methods such as TEM, SEM, EDS, BET, XRD, FTIR, zeta potential analysis, VSM, and TGA. The effects of palladium ion concentration, contact time, pH, and temperature on adsorption were evaluated. The kinetics were shown to follow the pseudo-second-order kinetic model and Elovich model, and the rate-limiting step was chemisorption. Thermodynamic studies showed that increasing the temperature promoted the adsorption of Pd(II), and the maximum uptake capacity of Fe3O4@MnO2@ZIF-67 for Pd(II) was 531.91 mg g−1. Interestingly, Fe3O4@MnO2@ZIF-67 exhibited superior selectivity for Pd(II) in the presence of Ir(IV), Pt(IV), and Rh(III). The adsorbent can be used repeatedly for selective adsorption of palladium. Even at the fifth cycle, the uptake rate of Pd(II) remained as high as 83.1%, and it showed a favorable adsorption capacity and selectivity for Pd(II) in real metallurgical wastewater. The adsorption mechanism was analyzed by SEM, FTIR, XRD, XPS, and DFT calculations, which indicated that electrostatic interactions and coordination with nitrogen-containing groups were involved. Fe3O4@MnO2@ZIF-67 is a promising adsorbent for the efficient adsorption and selective separation of palladium ions.

THU511 Somatostatin Analogs Or Active Surveillance In Sporadic And MEN1 Associated Non-functioning Pancreatic Neuroendocrine Tumors

Abstract Disclosure: S. Raia: None. S. Chiloiro: None. M. Maratta: None. B. Maiorano: None. E. Rossi: None. M. Brizi: None. V. Rufini: None. L. De Marinis: None. G. Rindi: None. G. Schinzari: None. A. Pontecorvi: None. G. Tortora: None. A. Bianchi: None. Introduction: Non-functioning (NF), sporadic and MEN1 associated, G1-G2 pancreatic neuroendocrine tumors (PanNETs) usually display an indolent course. Surgery is the first-choice treatment for localized tumors &amp;gt;2 cm. Unresectable or metastatic PanNETs expressing somatostatin receptors (SSTRs) are treated with somatostatin analogs (SSAs). The standard treatment for patients with PanNETs ≤2cm is active surveillance (AS). Yet no evidence of the value of SSA treatment exist in such patient population. Aim(s): To assess the clinical value of SSAs in patients with PanNETs ≤2cm. Material and methods: Data from patients (pts) NF, G1-G2 PanNETs≤2cm were retrospectively collected. Median progression-free survival (mPFS) and response rate (RR) were analyzed in SSA group and AS group. Results: From June 2007 to June 2022, data from 46 pts were considered: 29 pts, who declined an AS program but had not indication for surgery, entered in the SSA group (21 sporadic and 8 MEN1 associatd PanNET) and 17 in the AS group. At a median follow-up of 64.8 months for sporadic and of 63.9 for MEN1 associated PanNET, no disease progression (PD) was reported in the SSA group, without differences between sporadic and MEN1 associated PanNET. While the PD rate was 23.5 % in the AS group, with a mPFS of 36.2 months. Conclusion: SSAs therapy showed significant antiproliferative activity in patients with both sporadic and MEN1 associated NF, G1-G2 PanNETs ≤2cm. SSAs treatment delay tumor progression and distant spread in small lesions that sometimes may reveal an unpredictable aggressiveness. Presentation: Thursday, June 15, 2023