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1.
Commun Biol ; 7(1): 869, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020197

ABSTRACT

Electrokinetic convection-enhanced delivery (ECED) utilizes an external electric field to drive the delivery of molecules and bioactive substances to local regions of the brain through electroosmosis and electrophoresis, without the need for an applied pressure. We characterize the implementation of ECED to direct a neutrally charged fluorophore (3 kDa) from a doped biocompatible acrylic acid/acrylamide hydrogel placed on the cortical surface. We compare fluorophore infusion profiles using ECED (time = 30 min, current = 50 µA) and diffusion-only control trials, for ex vivo (N = 18) and in vivo (N = 12) experiments. The linear intensity profile of infusion to the brain is significantly higher in ECED compared to control trials, both for in vivo and ex vivo. The linear distance of infusion, area of infusion, and the displacement of peak fluorescence intensity along the direction of infusion in ECED trials compared to control trials are significantly larger for in vivo trials, but not for ex vivo trials. These results demonstrate the effectiveness of ECED to direct a solute from a surface hydrogel towards inside the brain parenchyma based predominantly on the electroosmotic vector.


Subject(s)
Brain , Convection , Drug Delivery Systems , Hydrogels , Hydrogels/chemistry , Brain/metabolism , Animals , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Fluorescent Dyes/chemistry , Fluorescent Dyes/administration & dosage , Male , Rats
2.
Sci Data ; 11(1): 601, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849407

ABSTRACT

Freshwater macroinvertebrates are a diverse group and play key ecological roles, including accelerating nutrient cycling, filtering water, controlling primary producers, and providing food for predators. Their differences in tolerances and short generation times manifest in rapid community responses to change. Macroinvertebrate community composition is an indicator of water quality. In Europe, efforts to improve water quality following environmental legislation, primarily starting in the 1980s, may have driven a recovery of macroinvertebrate communities. Towards understanding temporal and spatial variation of these organisms, we compiled the TREAM dataset (Time seRies of European freshwAter Macroinvertebrates), consisting of macroinvertebrate community time series from 1,816 river and stream sites (mean length of 19.2 years and 14.9 sampling years) of 22 European countries sampled between 1968 and 2020. In total, the data include >93 million sampled individuals of 2,648 taxa from 959 genera and 212 families. These data can be used to test questions ranging from identifying drivers of the population dynamics of specific taxa to assessing the success of legislative and management restoration efforts.


Subject(s)
Invertebrates , Rivers , Animals , Europe , Fresh Water , Population Dynamics , Water Quality , Biodiversity , Ecosystem
3.
J Chem Phys ; 160(19)2024 May 21.
Article in English | MEDLINE | ID: mdl-38747548

ABSTRACT

The efficient conversion of solar energy to chemical energy represents a critical bottleneck to the energy transition. Photocatalytic splitting of water to generate solar fuels is a promising solution. Semiconductor quantum dots (QDs) are prime candidates for light-harvesting components of photocatalytic heterostructures, given their size-dependent photophysical properties and band-edge energies. A promising series of heterostructured photocatalysts interface QDs with transition-metal oxides which embed midgap electronic states derived from the stereochemically active electron lone pairs of p-block cations. Here, we examine the thermodynamic driving forces and dynamics of charge separation in Sb2VO5/CdSe QD heterostructures, wherein a high density of Sb 5s2-derived midgap states are prospective acceptors for photogenerated holes. Hard-x-ray valence band photoemission spectroscopy measurements of Sb2VO5/CdSe QD heterostructures were used to deduce thermodynamic driving forces for charge separation. Interfacial charge transfer dynamics in the heterostructures were examined as a function of the mode of interfacial connectivity, contrasting heterostructures with direct interfaces assembled by successive ion layer adsorption and reaction (SILAR) and interfaces comprising molecular bridges assembled by linker-assisted assembly (LAA). Transient absorption spectroscopy measurements indicate ultrafast (<2 ps) electron and hole transfer in SILAR-derived heterostructures, whereas LAA-derived heterostructures show orders of magnitude differentials in the kinetics of hole (<100 ps) and electron (∼1 ns) transfer. The interface-modulated kinetic differentials in electron and hole transfer rates underpin the more effective charge separation, reduced charge recombination, and greater photocatalytic efficiency observed for the LAA-derived Sb2VO5/CdSe QD heterostructures.

4.
Transl Anim Sci ; 8: txae072, 2024.
Article in English | MEDLINE | ID: mdl-38745851

ABSTRACT

The objective of this meta-analysis was to develop and evaluate models for predicting nitrogen (N) excretion in feces, urine, and manure in beef cattle in South America. The study incorporated a total of 1,116 individual observations of N excretion in feces and 939 individual observations of N excretion in feces and in urine (g/d), representing a diverse range of diets, animal genotypes, and management conditions in South America. The dataset also included data on dry matter intake (DMI; kg/d) and nitrogen intake (NI; g/d), concentrations of dietary components, as well as average daily gain (ADG; g/d) and average body weight (BW; kg). Models were derived using linear mixed-effects regression with a random intercept for the study. Fecal N excretion was positively associated with DMI, NI, nonfibrous carbohydrates, average BW, and ADG and negatively associated with EE and CP concentration in the diet. The univariate model predicting fecal N excretion based on DMI (model 1) performed slightly better than the univariate model, which used NI as a predictor variable (model 2) with a root mean square error (RMSE) of 38.0 vs. 39.2%, the RMSE-observations SD ratio (RSR) of 0.81 vs. 0.84, and concordance correlation coefficient (CCC) of 0.53 vs. 0.50, respectively. Models predicting urinary N excretion were less accurate than those derived to predict fecal N excretion, with an average RMSE of 43.7% vs. 37.0%, respectively. Urinary and manure N excretion were positively associated with DMI, NI, CP, average BW, and ADG and negatively associated with neutral detergent fiber concentration in the diet. As opposed to fecal N excretion, the univariate model predicting urinary N excretion using NI (model 10) performed slightly better than the univariate model using DMI (model 9) as predictor variable with an RMSE of 36.0% vs. 39.7%, RSR 0.85 vs. 0.93, and CCC of 0.43 vs. 0.29, respectively. The models developed in this study are applicable for predicting N excretion in beef cattle across a broad spectrum of dietary compositions and animal genotypes in South America. The univariate model using DMI as a predictor is recommended for fecal N prediction, while the univariate model using NI is recommended for predicting urinary and manure N excretion because the use of more complex models resulted in little to no benefits. However, it may be more useful to consider more complex models that incorporate nutrient intakes and diet composition for decision-making when N excretion is a factor to be considered. Three extant equations evaluated in this study have the potential to be used in tropical conditions typical of South America to predict fecal N excretion with good precision and accuracy. However, none of the extant equations are recommended for predicting urine or manure N excretion because of their high RMSE, and low precision and accuracy.

5.
World Neurosurg ; 187: e1062-e1071, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38744375

ABSTRACT

OBJECTIVES: The modified 5-item frailty index (mFI-5) is a comorbidity-based risk stratification tool to predict adverse events following various neurologic surgeries. This study aims to quantify the association between increased mFI-5 and postoperative complications and mortality following surgical fixation of traumatic thoracolumbar fractures. METHODS: The 2011-2021 American College of Surgeons - National Surgical Quality Improvement Program (ACS-NSQIP) dataset was used to identify patients undergoing fusion surgeries for thoracolumbar spine fractures. The mFI-5 score was calculated based on the presence of 5 major comorbidities: congestive heart failure within 30 days before surgery, insulin-dependent or noninsulin-dependent diabetes mellitus, chronic obstructive pulmonary disease, partially dependent or totally dependent functional health status at the time of surgery, and hypertension requiring medication. Multivariate analysis assessed the independent impact of increasing mFI-5 scores on postoperative 30-day morbidity and mortality while controlling for baseline clinical characteristics. RESULTS: A total of 66,904 patients were included in our analysis (54.2% female, mean age 62.27 ± 12.93 years). On univariate analysis, higher mFI-5 score was significantly associated with increased risks of superficial surgical site infection, deep surgical site infection, wound dehiscence, unplanned reoperation, pneumonia, unplanned intubation, postoperative ventilator use, progressive renal insufficiency, acute renal failure, urinary tract infection, stroke, myocardial infarction, cardiac arrest, pulmonary embolism, deep vein thrombosis, bleeding requiring transfusion, sepsis, septic shock, and longer hospital length of stay (LOS). On multivariate logistic regression, increasing mFI-5 score versus a mFI-5 score of zero was associated with higher odds of overall complications (mFI-5 ≥2: odds ratio [OR] 1.38 CI: 1.24-1.54, P < 0.001; mFI-5 = 1: OR 1.18 CI: 1.11-1.24, P < 0.001) and 30-day mortality (mFI-5 ≥2: OR 2.33 CI: 1.60-3.38, P < 0.001). CONCLUSION: This study demonstrates that frailty, when measured using the mFI-5, independently predicts postoperative complications, hospital LOS, and 30-day mortality after surgical repair of thoracolumbar fractures. These findings are important for risk stratification in patients undergoing thoracolumbar fusion surgery and for standardization in reporting outcomes after those procedures.


Subject(s)
Frailty , Lumbar Vertebrae , Postoperative Complications , Spinal Fractures , Thoracic Vertebrae , Humans , Female , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/mortality , Thoracic Vertebrae/surgery , Thoracic Vertebrae/injuries , Spinal Fractures/surgery , Spinal Fractures/mortality , Aged , Lumbar Vertebrae/surgery , Frailty/complications , Spinal Fusion/adverse effects , Spinal Fusion/methods
6.
World Neurosurg ; 188: e34-e40, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38710406

ABSTRACT

OBJECTIVE: This study aims to assess race as an independent risk factor for postoperative complications after surgical fixation of traumatic thoracolumbar fractures for African American and Asian American patients compared with White patients. METHODS: The 2011-2021 American College of Surgeons - National Surgical Quality Improvement Program (ACS-NSQIP) dataset was used to identify patients undergoing fusion surgeries for thoracolumbar spine fractures. Patient comorbidity burden was assessed using a modified 5-item frailty index score (mFI-5). Chi-squared and ANOVA tests were used to compare baseline clinical characteristics between groups. Multivariate analysis was performed to compare African American and Asian American patients with White patients controlling for age, BMI, and American Society of Anesthesiologists (ASA) score. RESULTS: African American patients experienced longer operative times compared to Asian American and White patients (3.74 ± 1.87 hours vs. 3.04 ± 1.71 hours and 3.48 ± 1.81 hours, P < 0.001). African American and Asian American patients demonstrated higher comorbidity burden with mFI-5>2 compared to White patients (30.7% and 25.6% vs. 19.9%, P < 0.001). African American and Asian American patients had a higher risk of postoperative complications than White patients (22.4% and 20% vs. 19.7%, P < 0.001). African American race was an independent risk factor of postoperative 30-day morbidity (OR 1.19, CI 1.11-1.28, P < 0.001). CONCLUSIONS: African American and Asian American patients undergoing thoracolumbar fusion surgeries exhibit disproportionate comorbidity burden, longer LOS, and greater postoperative complications compared with White patients. Furthermore, the African American race was associated with an increased rate of 30-day postoperative complications.


Subject(s)
Lumbar Vertebrae , Postoperative Complications , Spinal Fractures , Thoracic Vertebrae , Adult , Aged , Female , Humans , Male , Middle Aged , Asian , Black or African American , Databases, Factual , Healthcare Disparities/ethnology , Lumbar Vertebrae/surgery , Lumbar Vertebrae/injuries , Operative Time , Postoperative Complications/epidemiology , Postoperative Complications/ethnology , Risk Factors , Spinal Fractures/surgery , Spinal Fractures/ethnology , Spinal Fusion , Thoracic Vertebrae/surgery , Thoracic Vertebrae/injuries , Treatment Outcome , United States/epidemiology , White
7.
Int J Mol Sci ; 25(10)2024 May 10.
Article in English | MEDLINE | ID: mdl-38791228

ABSTRACT

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals effectively. This review is a summary of current information about CGA, including its natural sources, biosynthesis, metabolism, toxicology, role in combatting chemoresistance, and protective effects against chemotherapy-induced toxicity. It also emphasizes the potential of CGA as a pharmacological adjuvant in cancer treatment with drugs such as 5-fluorouracil, cisplatin, oxaliplatin, doxorubicin, regorafenib, and radiotherapy. By analyzing more than 140 papers from PubMed, Google Scholar, and SciFinder, we hope to find the therapeutic potential of CGA in improving cancer therapy.


Subject(s)
Chlorogenic Acid , Drug Resistance, Neoplasm , Neoplasms , Humans , Chlorogenic Acid/pharmacology , Chlorogenic Acid/therapeutic use , Neoplasms/drug therapy , Neoplasms/metabolism , Drug Resistance, Neoplasm/drug effects , Animals , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology
8.
Nat Prod Res ; : 1-6, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38567750

ABSTRACT

Polysaccharides from wood-rooting fungi have attracted attention due to their broad pharmacological properties. Herein, we report the antitumor and immunomodulatory activities of acid polysaccharides isolated from fungi Gloeosoma mirabile. The polysaccharide extracts displayed significant antiproliferative activity against cancer cell lines (MCF-7, HCT-116, U-937) in a dose-dependent manner and induction of IL-6 in macrophage RAW 264.7. Furthermore, flow cytometry analysis showed that high polysaccharide concentrations induced apoptosis by 83% in HL-60 cells. Based on gas chromatography-mass spectrometry (GC-MS) and Fourier transform infra-red (FT-IR) spectroscopy studies, acidic polysaccharides from G. mirabile were mainly composed of arabinose, α-D-galactopyranose and methyl ß-D-galactopyranoside.

9.
J Arthroplasty ; 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38364878

ABSTRACT

BACKGROUND: Anterior knee pain (AKP) following total knee arthroplasty (TKA) with patellar preservation is a common complication that significantly affects patients' quality of life. This study aimed to develop a machine-learning model to predict the likelihood of developing AKP after TKA using radiological variables. METHODS: A cohort of 131 anterior stabilized TKA cases (105 patients) without patellar resurfacing was included. Patients underwent a follow-up evaluation with a minimum 1-year follow-up. The primary outcome was AKP, and radiological measurements were used as predictor variables. There were 2 observers who made the radiological measurement, which included lower limb dysmetria, joint space, and coronal, sagittal, and axial alignment. Machine-learning models were applied to predict AKP. The best-performing model was selected based on accuracy, precision, sensitivity, specificity, and Kappa statistics. Python 3.11 with Pandas and PyCaret libraries were used for analysis. RESULTS: A total of 35 TKA had AKP (26.7%). Patient-reported outcomes were significantly better in the patients who did not have AKP. The Gradient Boosting Classifier performed best for both observers, achieving an area under the curve of 0.9261 and 0.9164, respectively. The mechanical tibial slope was the most important variable for predicting AKP. The Shapley test indicated that high/low mechanical tibial slope, a shorter operated leg, a valgus coronal alignment, and excessive patellar tilt increased AKP risk. CONCLUSIONS: The results suggest that global alignment, including sagittal, coronal, and axial alignment, is relevant in predicting AKP after TKA. These findings provide valuable insights for optimizing TKA outcomes and reducing the incidence of AKP.

10.
Int J Gynecol Cancer ; 34(4): 504-509, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38378695

ABSTRACT

OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. RESULTS: Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. CONCLUSION: Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.


Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/pathology , Lymphatic Metastasis/pathology , Consensus , Lymph Node Excision/methods , Sentinel Lymph Node Biopsy/methods , Indocyanine Green , Lymph Nodes/pathology
12.
Science ; 383(6679): 183-189, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38207020

ABSTRACT

A dense system of pre-Hispanic urban centers has been found in the Upano Valley of Amazonian Ecuador, in the eastern foothills of the Andes. Fieldwork and light detection and ranging (LIDAR) analysis have revealed an anthropized landscape with clusters of monumental platforms, plazas, and streets following a specific pattern intertwined with extensive agricultural drainages and terraces as well as wide straight roads running over great distances. Archaeological excavations date the occupation from around 500 BCE to between 300 and 600 CE. The most notable landscape feature is the complex road system extending over tens of kilometers, connecting the different urban centers, thus creating a regional-scale network. Such extensive early development in the Upper Amazon is comparable to similar Maya urban systems recently highlighted in Mexico and Guatemala.

13.
Crit Care Explor ; 6(1): e1034, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38259864

ABSTRACT

OBJECTIVES: To explore gamification as an alternative approach to healthcare education and its potential applications to critical care. DATA SOURCES: English language manuscripts addressing: 1) gamification theory and application in healthcare and critical care and 2) implementation science focused on the knowledge-to-practice gap were identified in Medline and PubMed databases (inception to 2023). STUDY SELECTION: Studies delineating gamification underpinnings, application in education or procedural mentoring, utilization for healthcare or critical care education and practice, and analyses of benefits or pitfalls in comparison to other educational or behavioral modification approaches. DATA EXTRACTION: Data indicated the key gamification tenets and the venues within which they were used to enhance knowledge, support continuing medical education, teach procedural skills, enhance decision-making, or modify behavior. DATA SYNTHESIS: Gamification engages learners in a visual and cognitive fashion using competitive approaches to enhance acquiring new knowledge or skills. While gamification may be used in a variety of settings, specific design elements may relate to the learning environment or learner styles. Additionally, solo and group gamification approaches demonstrate success and leverage adult learning theory elements in a low-stress and low-risk setting. The potential for gamification-driven behavioral modification to close the knowledge-to-practice gap and enable guideline and protocol compliance remains underutilized. CONCLUSIONS: Gamification offers the potential to substantially enhance how critical care professionals acquire and then implement new knowledge in a fashion that is more engaging and rewarding than traditional approaches. Accordingly, educational undertakings from courses to offerings at medical professional meetings may benefit from being gamified.

14.
J Neural Eng ; 21(1)2024 02 01.
Article in English | MEDLINE | ID: mdl-38237175

ABSTRACT

Peripheral nerve interfaces (PNIs) are electrical systems designed to integrate with peripheral nerves in patients, such as following central nervous system (CNS) injuries to augment or replace CNS control and restore function. We review the literature for clinical trials and studies containing clinical outcome measures to explore the utility of human applications of PNIs. We discuss the various types of electrodes currently used for PNI systems and their functionalities and limitations. We discuss important design characteristics of PNI systems, including biocompatibility, resolution and specificity, efficacy, and longevity, to highlight their importance in the current and future development of PNIs. The clinical outcomes of PNI systems are also discussed. Finally, we review relevant PNI clinical trials that were conducted, up to the present date, to restore the sensory and motor function of upper or lower limbs in amputees, spinal cord injury patients, or intact individuals and describe their significant findings. This review highlights the current progress in the field of PNIs and serves as a foundation for future development and application of PNI systems.


Subject(s)
Amputees , Peripheral Nerves , Humans , Amputation, Surgical , Electrodes , Paralysis/surgery
15.
Cancer Discov ; 14(1): 120-141, 2024 01 12.
Article in English | MEDLINE | ID: mdl-37934001

ABSTRACT

Failure of adoptive T-cell therapies in patients with cancer is linked to limited T-cell expansion and persistence, even in memory-prone 41BB-(BBz)-based chimeric antigen receptor (CAR) T cells. We show here that BBz-CAR T-cell stem/memory differentiation and persistence can be enhanced through epigenetic manipulation of the histone 3 lysine 9 trimethylation (H3K9me3) pathway. Inactivation of the H3K9 trimethyltransferase SUV39H1 enhances BBz-CAR T cell long-term persistence, protecting mice against tumor relapses and rechallenges in lung and disseminated solid tumor models up to several months after CAR T-cell infusion. Single-cell transcriptomic (single-cell RNA sequencing) and chromatin opening (single-cell assay for transposase accessible chromatin) analyses of tumor-infiltrating CAR T cells show early reprogramming into self-renewing, stemlike populations with decreased expression of dysfunction genes in all T-cell subpopulations. Therefore, epigenetic manipulation of H3K9 methylation by SUV39H1 optimizes the long-term functional persistence of BBz-CAR T cells, limiting relapses, and providing protection against tumor rechallenges. SIGNIFICANCE: Limited CAR T-cell expansion and persistence hinders therapeutic responses in solid cancer patients. We show that targeting SUV39H1 histone methyltransferase enhances 41BB-based CAR T-cell long-term protection against tumor relapses and rechallenges by increasing stemness/memory differentiation. This opens a safe path to enhancing adoptive cell therapies for solid tumors. See related article by Jain et al., p. 142. This article is featured in Selected Articles from This Issue, p. 5.


Subject(s)
Neoplasms , Receptors, Chimeric Antigen , Animals , Humans , Mice , Chromatin , Immunotherapy, Adoptive , Methyltransferases/genetics , Methyltransferases/metabolism , Neoplasms/genetics , Neoplasms/therapy , Recurrence , Repressor Proteins/genetics , Repressor Proteins/metabolism
16.
Future Oncol ; 20(7): 351-360, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37994649

ABSTRACT

WHAT IS THIS SUMMARY ABOUT?: This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder. WHAT WERE THE RESULTS?: In the 45 patients studied, around 16% did have serious side effects, but most side effects were manageable. Twenty-four percent of patients, however, stopped the study treatment because of their side effects. Within about 2 months of starting treatment, most patients' (73%) tumors were smaller and stayed smaller, on average, for more than 2 years. WHAT DO THE RESULTS MEAN?: The combination of enfortumab vedotin plus pembrolizumab is a new treatment option for patients with locally advanced or metastatic urothelial cancer when they cannot receive the typical treatment, cisplatin. Advanced or metastatic urothelial cancer is a type of cancer where the cancer has already spread outside of the bladder or urinary tract.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Urologic Neoplasms , Humans , Urologic Neoplasms/drug therapy , Urologic Neoplasms/pathology , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal/adverse effects , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology
17.
Eur J Cancer ; 196: 113434, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38008031

ABSTRACT

BACKGROUND: Accumulation of the HIF-2α transcription factor is an oncogenic event implicated in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). In the phase I LITESPARK-001 study, the first-in-class HIF-2α inhibitor belzutifan demonstrated antitumor activity and an acceptable safety profile for pretreated patients with advanced ccRCC. Updated data with additional follow-up of > 40 months are presented. METHODS: LITESPARK-001 is an ongoing open-label study with a 3 + 3 dose-escalation design followed by an expansion phase. Patients with ccRCC enrolled at 7 sites received belzutifan 120 mg orally once daily until disease progression, unacceptable toxicity, or patient withdrawal. The data cutoff date was July 15, 2021. The primary end point was identifying the maximum tolerated dose and/or the recommended phase II dose. Secondary end points included objective response rate (ORR) and duration of response (DOR) per RECIST v1.1 by investigator assessment and safety. RESULTS: Median follow-up was 41.2 months (range, 38.2-47.7). Patients received a median of 3 (range, 1-9) prior systemic therapies. Of 55 patients, 14 (25 %) achieved an objective response. Median DOR was not reached (range, 3.1 + to 38.0 + months). Adverse events (AEs) attributed to study treatment by investigator assessment were reported in 53 patients (96 %). 22 patients (40 %) had grade 3 treatment-related AEs; the most common were anemia (n = 13; 24 %) and hypoxia (n = 7; 13 %). No grade 4 or 5 treatment-related AEs occurred. CONCLUSION: After a median follow-up of 41.2 months, belzutifan monotherapy demonstrated durable antitumor activity in patients with advanced ccRCC and acceptable safety. CLINICALTRIALS: gov. NCT02974738.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Follow-Up Studies , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Basic Helix-Loop-Helix Transcription Factors/therapeutic use
18.
Oper Neurosurg (Hagerstown) ; 26(3): 309-313, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37890096

ABSTRACT

BACKGROUND AND OBJECTIVES: Intrathecal drug therapy is a common treatment for dystonia, pain, and spasticity using implanted pump and catheter systems. Standardized management of intrathecal drug pump (ITDP) migration and flipping has not been well established in the literature. This study reports the use of soft tissue to address less common pump complications such as pump flipping, migration, and difficulty in medication refill. METHODS: A retrospective chart review of intrathecal pump cases performed by two surgeons between February 2020 and August 2022 was conducted. Patients with complications such as pump flipping, migration, or challenges in medication refill treated with soft tissue flaps were included. Patient demographics, comorbidities, and perioperative data were collected. RESULTS: A total of five patients with ITDP complicated by pump flipping, migration, malposition, or difficulty in medication refill that were treated using fascial flaps were included in the study. Three technical considerations when revising ITDP complications are secure pump anchoring, reliable wound closure, and ease of pump medication refill. Cases 1 and 2 demonstrate the technique of secure pump anchoring with a rectus fascial flap. Cases 3 and 4 show a technique to achieve reliable vascularized wound closure, and case 5 describes a technique to solve an uncommon problem of a thick subcutaneous abdominal tissue preventing the refill of the ITDP medication. CONCLUSION: Soft tissue flaps may serve as a treatment option for patients with uncommon ITDP complications. De-epithelialized dermal fasciocutaneous or fascial flaps may be developed to anchor the pump more securely. Cross-discipline collaboration may further delineate the technique, benefits, and outcomes of this approach.


Subject(s)
Infusion Pumps, Implantable , Surgical Flaps , Humans , Retrospective Studies , Infusion Pumps, Implantable/adverse effects , Muscle Spasticity/drug therapy , Muscle Spasticity/surgery , Muscle Spasticity/etiology , Abdomen
20.
PeerJ ; 11: e16533, 2023.
Article in English | MEDLINE | ID: mdl-38099301

ABSTRACT

The avifauna of South America is one of the most widely studied groups of vertebrates. However, certain species, such as the Andean Ibis (Theristicus branickii), have received limited attention regarding their ecological patterns, biology, current distribution, and environmental requirements. This study analyzed observation data from the Global Biodiversity Information Facility (GBIF) on the Andean Ibis in four countries to identify and understand critical variables that determine the species' presence, assess the proportion of its habitat within protected areas and identify possible threats to the species. Additionally, this study considered environmental and ecological variables to model ecological niches using the maximum entropy approach in MaxEnt to map the suitable habitat of the species. The findings revealed the extent of suitable Andean Ibis habitats in Ecuador, Peru, Bolivia and Chile. The variables that most determined the presence of the species were: altitude (36.57%), distance to lakes (23.29%) and ecological isothermality (13.34%). The distribution area of the Andean Ibis totaled 300,095.00 km2, spanning both sides of the Andean mountains range. Human activities have left a significant impact on the Andean Ibis habitat, with 48% of this area impacted by the human footprint and only 10% of the territory falling within protected areas designated by the respective countries. The results of this study show that the Andean Ibis presents characteristics of a specialist species due to its adaptation to the climate conditions of the plateau and highlands, including low temperatures, herbaceous vegetation and the presence of water bodies. The species is distributed in disconnected Andean landscape areas, whose functionality could be compromised by increased human activities. Complementary studies will be necessary to understand the ecological role and effectiveness of protected areas for conserving the species.


Subject(s)
Birds , Animals , Humans , Peru , Ecuador , Bolivia , Chile
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