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1.
J Clin Anesth ; 98: 111588, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39173241

RESUMO

STUDY OBJECTIVE: To compare the effects of neostigmine/glycopyrrolate (a traditional agent) and sugammadex on bowel motility recovery and the occurrence of digestive system complications after colorectal surgery. DESIGN: Prospective, randomized controlled trial. SETTING: A single tertiary center. PATIENTS: 111 patients undergoing laparoscopic colorectal surgery. INTERVENTIONS: Patients were randomized into two groups based on the block reversal agent: 1) a mixture of 50 µg.kg-1 of neostigmine and 10 µg.kg-1 of glycopyrrolate (neostigmine group) and 2) 2 mg.kg-1 of sugammadex (sugammadex group). MEASUREMENTS: The primary outcome was the time from the surgery's completion to the first flatus. The time to the first postoperative defecation, incidences of postoperative nausea or vomiting, ileus, and dry mouth, as well as postoperative length of stay, were also assessed. MAIN RESULTS: The time to the first flatus was significantly shorter in the sugammadex group than in the neostigmine group (59 [42-79] h vs 69 [53-90] h, P = 0.027). The time to the first defecation and the incidences of postoperative nausea or vomiting and ileus did not differ between the groups, nor did the postoperative length of stay. However, the incidence of postoperative dry mouth was significantly lower in the sugammadex group than in the neostigmine group (7 patients [13%] vs 39 patients [71%], P < 0.001). CONCLUSIONS: The time to the first flatus was shorter using 2 mg.kg-1 sugammadex to reverse the neuromuscular block for laparoscopic colorectal surgery compared to reversal with conventional neostigmine/glycopyrrolate.

2.
Cell Death Dis ; 15(8): 589, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138148

RESUMO

It is still challenging to predict the efficacy of cisplatin-based therapy, particularly in relation to the activation of macroautophagy/autophagy in oral squamous cell carcinoma (OSCC). We studied the effect of selected chromatin remodeling genes on the cisplatin resistance and their interplay with autophagy in 3-dimensional tumor model and xenografts. We analyzed gene expression patterns in the cisplatin-sensitive UMSCC1, and a paired cisplatin-resistant UM-Cis cells. Many histone protein gene clusters involved in nucleosome assembly showed significant difference of expression. Gain- and loss-of-function analyses revealed an inverse correlation between cisplatin resistance and HIST1H3D expression, while a positive correlation was observed with HIST3H2A or HIST3H2B expression. In UM-Cis, HIST3H2A- and HIST3H2B-mediated chromatin remodeling upregulates autophagy status, which results in cisplatin resistance. Additionally, knockdown of HIST3H2A or HIST3H2B downregulated autophagy-activating genes via chromatin compaction of their promoter regions. MiTF, one of the key autophagy regulators upregulated in UM-Cis, negatively regulated transcription of HIST1H3D, suggesting an interplay between chromatin remodeling-dependent cisplatin resistance and autophagy. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, protein expression pattern of the selected histone protein genes were matched with the in vitro data. By examining the relationship between autophagy and chromatin remodeling genes, we identified a set of candidate genes with potential use as markers predicting chemoresistance in OSCC biopsy samples.


Assuntos
Autofagia , Carcinoma de Células Escamosas , Montagem e Desmontagem da Cromatina , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Bucais , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Humanos , Autofagia/efeitos dos fármacos , Autofagia/genética , Resistencia a Medicamentos Antineoplásicos/genética , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Histonas/metabolismo , Camundongos Nus , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Small ; : e2404251, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39175372

RESUMO

Peripheral vascular interventions (PVIs) offer several benefits to patients with lower extremity arterial diseases, including reduced pain, simpler anesthesia, and shorter recovery time, compared to open surgery. However, to monitor the endovascular tools inside the body, PVIs are conducted under X-ray fluoroscopy, which poses serious long-term health risks to physicians and patients. Shortwave infrared (SWIR) imaging of quantum dots (QDs) has shown great potential in bioimaging due to the non-ionizing penetration of SWIR light through tissues. In this paper, a QD-based magnetic guidewire and its system is introduced that allows X-ray-free detection under SWIR imaging and precise steering via magnetic manipulation. The QD magnetic guidewire contains a flexible silicone tube encapsulating a QD polydimethylsiloxane (PDMS) composite, where HgCdSe/HgS/CdS/CdZnS/ZnS/SiO2 core/multi-shell QDs are dispersed in the PDMS matrix for SWIR imaging upon near-infrared excitation, as well as a permanent magnet for magnetic steering. The SWIR penetration of the QD magnetic guidewire is investigated within an artificial tissue model (1% Intralipid) and explore the potential for non-fluoroscopic PVIs within a vascular phantom model. The QD magnetic guidewire is biocompatible in its entirety, with excellent resistance to photobleaching and chemical alteration, which is a promising sign for its future clinical implementation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39177114

RESUMO

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the usefulness of corner osteotomy (CO) in patients with adult spinal deformity (ASD) by comparing with pedicle subtraction osteotomy (PSO) for lordosis correction. SUMMARY OF BACKGROUND DATA: PSO remains a valuable procedure for patients with ASD, but it has a limit to obtaining correction angles exceeding 45° in patients with a large pelvic incidence or with previous spinal fusion surgeries. Theoretically, CO can exceed the limitation of PSO and can achieve a wide range of correction angles. However, no study has analyzed the clinical data and usefulness of CO. METHODS: This study included 115 patients (mean age 71.1 y, mean follow-up period 78.9 mo) with ASD who underwent deformity correction using PSO or CO. Comparative analysis was performed on spinopelvic parameters including segmental angle (SA) around the osteotomy site, and clinical and surgical assessment between the PSO and corner groups. RESULTS: In the corner group, the postoperative SA (35° vs. -39.3°, P=0.004) and the degree of SA correction (34.8° vs. 39.7°, P=0.004) were greater, and a broader range of SA correction was also possible (18-51° vs. 18-61°). Although the operative time was longer in the corner group (316.8 min vs. 342.3 min, P=0.014), the estimated blood loss (EBL) was lower (2841.3 mL vs. 2465.4 mL, P=0.032). There was no difference in major complication rates, but the frequency of rod fracture (RF) was lower in the corner group (36/27 vs. 1/51, P<0.05). CONCLUSION: CO showed a greater SA correction and achieved a broader range of SA correction angles than PSO with no difference in the incidence of major complications. In addition, the EBL and the frequency of RF were lower. Based on these results, we expect that CO can serve as a promising surgical alternative to PSO for spinal deformity correction among patients with ASD.

5.
EJHaem ; 5(4): 690-697, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39157592

RESUMO

Serious infection is common in patients with multiple myeloma due to immune deficiency from the underlying disease and/or its treatment. Immunoglobulin replacement is one approach to reduce infection risk in these patients. However, few real-world data exist on its use in patients with myeloma. We investigated immunoglobulin use in Australia, New Zealand and Asia-Pacific using registry data and explored its association with survival outcomes. A total of 2374 patients with a median follow-up time of 29.5 months (interquartile range 13.3-54.3 months) were included in the analysis - 1673 from Australia, 313 Korea, 281 New Zealand and 107 Singapore. Overall, 7.1% of participants received immunoglobulin replacement within 24 months of diagnosis. Patients who received immunoglobulin replacement were likely to be younger, had lower baseline IgG levels (excluding paraprotein), were more likely to have baseline hypogammaglobulinaemia, baseline severe hypogammaglobulinaemia and abnormal baseline fluorescent in-situ hybridisation status, receive first-line myeloma treatment with immunomodulatory drugs or anti-CD38 therapy and undergo upfront autologous stem cell transplant. In our patient cohort, the use of immunoglobulin was not associated with overall survival benefit at the time of last follow-up (adjusted hazard ratio 0.72, 95% CI 0.46-1.14, p = 0.16). Understanding treatment approaches in clinical practice can help support future planning and provision of immunoglobulin resources.

6.
J Neurosurg Case Lessons ; 8(8)2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39159496

RESUMO

BACKGROUND: In recent developments, full endoscopic and unilateral biportal endoscopic (UBE) spine surgery have emerged to aid the transforaminal lumbar interbody fusion (TLIF) procedure. Yet, both approaches present a challenge due to limited space for cage insertion, potentially leading to complications such as cage subsidence or nonfusion in long-term assessments. Utilizing double cages may mitigate these concerns. This paper presents a unique case in which a patient successfully underwent computed tomography (CT) navigation-guided UBE-TLIF with 2 converging cages, highlighting the potential benefits and feasibility of this innovative approach. OBSERVATIONS: A 59-year-old female diagnosed with degenerative spondylolisthesis at the L4-5 level underwent a UBE-TLIF. The operation is detailed step by step and supported by illustrative figures and surgical videos. Postsurgery results revealed a significant improvement in the patient's condition, with the visual analog scale score decreasing from 7 to 3 on the first day, leading to a satisfaction rate of 90% at the last follow-up. LESSONS: Utilizing endoscopic visualization complemented by contrast medium has substantially elevated the quality of disc preparation. From their observations, the authors affirm that the integration of intraoperative CT navigation systems significantly augments safety and pinpoint accuracy in UBE-TLIF procedures. The strategy of employing 2 converging cages through a unilateral technique stands as a practical solution, potentially optimizing the fusion outcomes of UBE-TLIF surgery. https://thejns.org/doi/10.3171/CASE23512.

7.
J Korean Med Sci ; 39(32): e229, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39164054

RESUMO

BACKGROUND: We aimed to evaluate long-term outcomes of gamma knife radiosurgery (GKS) for cerebral cavernous malformations (CCMs). METHODS: Among the 233 CCM patients who underwent GKS, 79 adult patients (96 lesions) followed for over 10 years were included and analyzed retrospectively. Annual hemorrhage rate (AHR) was analyzed the entire cohort of 233 patients and the subset of 79 enrolled patients by dividing lesions into overall CCM lesions and brainstem lesions. AHR, neurologic outcome, adverse radiation effect (ARE), and changes of lesions in magnetic resonance imaging (MRI) were compared before and after GKS. Cox-regression analysis was performed to identify risk factors for hemorrhage following GKS. RESULTS: Mean follow-up duration of 79 enrolled patients was 14 years (range, 10-23 years). The AHR of all CCMs for entire cohort at each time point was 17.8% (pre-GKS), 5.9% (≤ 2 years post-GKS), 1.8% (≤ 10 years post-GKS). The AHR of all CCM for 79 enrolled patients was 21.4% (pre-GKS), 3.8% (2 years post-GKS), 1.4% (10 years post-GKS), and 2.3% (> 10 years post-GKS). The AHR of brainstem cavernous malformation (CM) for entire cohort at each time point was 22.4% (pre-GKS), 10.1% (≤ 2 years post-GKS), 3.2% (≤ 10 years post-GKS). The AHR of brainstem CM for 79 enrolled patients was 27.2% (pre-GKS), 5.8% (2 years post-GKS), 3.4% (10 years post-GKS), and 3.5% (> 10 years post-GKS). Out of the 79 enrolled patients, 35 presented with focal neurologic deficits at the initial clinical visit. Among these patients, 74.3% showed recovery at the last follow-up. Symptomatic ARE occurred in five (6.4%) patients. No mortality occurred. Most lesions were decreased in size at the last follow-up MRI. Previous hemorrhage history (hazard ratio [HR], 8.38; 95% confidence interval [CI], 1.07-65.88; P = 0.043), and brainstem location (HR, 3.10; 95% CI, 1.26-7.64; P = 0.014) were significant risk factors for hemorrhage event. CONCLUSION: GKS for CCM showed favorable long-term outcomes. GKS should be considered for CCM, especially when it has a previous hemorrhage history and brainstem location.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Imageamento por Ressonância Magnética , Radiocirurgia , Humanos , Adulto , Masculino , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem , Adolescente , Seguimentos , Modelos de Riscos Proporcionais , Idoso , Fatores de Risco , Tronco Encefálico/patologia , Tronco Encefálico/diagnóstico por imagem
8.
Cancer Res Treat ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39118525

RESUMO

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of TCGA and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in disease control rate per the TP53 mutation status (p=0.503); however, female patients with TP53 mutated (MT) had a significantly prolonged median progression-free survival (PFS) compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). PD-L1 high (≥50%) expression was significantly enriched in female patients with TP53 MT (p=0.001). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p<0.001). In TCGA analysis, expression of immune-related genes, and TMB score in TP53 MT females were higher than in males without TP53 MT. Conclusion: Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

9.
Chemosphere ; : 143108, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39151586

RESUMO

In the previous study (Im et al., 2022), we revealed microplastic (MP) was accumulated and cleared through the kidneys via PET imaging. Here, we aimed to identify the renal dysfunction due to polyethylene (PE) MP in the kidney tissue. Mice were exposed to 100 ppm (∼equivalent to 0.1mg/mL) /100 µL of PE for 12 weeks (n =10). PE uptake in the kidney tissues was confirmed using confocal microscopy. QuantSeq analysis was performed to determine gene expression. Renal function assessment was performed using 99mTc-Diethylene triamine penta acetic acid or 99mTc-Dimercaptosuccinic acid. Measurement of creatinine, BUN, and albumin levels in serum and urine samples was also estimated. [18F]-FDG was also acquired. PE increased expression of Myc, CD44, Programmed Death-Ligand 1 (PD-L1), and Hypoxia-Inducible Factor (HIF)-1α, which indicates a potential link to an increased risk of early-onset cancer. An increase in glucose metabolism of [18F]-FDG were observed. We assessed renal failure using 99mTc-Diethylene triamine penta acetic acid and 99mTc-Dimercaptosuccinic acid scintigraphy to determine the renal function. Renal failure was confirmed using serum and urine creatinine, serum blood urea nitrogen levels, serum albumin levels, and urine albumin levels in PE exposed mice, relative to the control. In sum, PE exposure induced renal dysfunction in a murine model.

10.
Acc Chem Res ; 57(16): 2395-2413, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39101684

RESUMO

ConspectusGas sensors are used in various applications to sense toxic gases, mainly for enhanced safety. Resistive sensors are particularly popular owing to their ability to detect trace amounts of gases, high stability, fast response times, and affordability. Semiconducting metal oxides are commonly employed in the fabrication of resistive gas sensors. However, these sensors often require high working temperatures, bringing about increased energy consumption and reduced selectivity. Furthermore, they do not have enough flexibility, and their performance is significantly decreased under bending, stretching, or twisting. To address these challenges, alternative materials capable of operating at lower temperatures with high flexibility are needed. Two-dimensional (2D) materials such as MXenes and transition-metal dichalcogenides (TMDs) offer high surface area and conductivity owing to their unique 2D structure, making them promising candidates for realization of resistive gas sensors. Nevertheless, their sensing performance in pristine form is typically weak and unacceptable, particularly in terms of response, selectivity, and recovery time (trec). To overcome these drawbacks, several strategies can be employed to enhance their sensing properties. Noble-metal decoration such as (Au, Pt, Pd, Rh, Ag) is a highly promising method, in which the catalytic effects of noble metals as well as formation of potential barriers with MXenes or TMDs eventually contribute to boosted response. Additionally, bimetallic noble metals such as Pt-Pd and Au/Pd with their synergistic properties can further improve sensor performance. Ion implantation is another feasible approach, involving doping of sensing materials with the desired concentration of dopants through control over the energy and dosage of the irradiation ions as well as creation of structural defects such as oxygen vacancies through high-energy ion-beam irradiation, contributing to enhanced sensing capabilities. The formation of core-shell structures is also effective, creating numerous interfaces between core and shell materials that optimize the sensing characteristics. However, the shell thickness needs to be carefully optimized to achieve the best sensing output. To reduce energy consumption, sensors can operate in a self-heating condition where an external voltage is applied to the electrodes, significantly lowering the power requirements. This enables sensors to function in energy-constrained environments, such as remote or low-energy areas. An important advantage of 2D MXenes and TMDs is their high mechanical flexibility. Unlike semiconducting metal oxides that lack mechanical flexibility, MXenes and TMDs can maintain their sensing performance even when integrated onto flexible substrates and subjected to bending, tilting, or stretching. This flexibility makes them ideal for fabricating flexible and portable gas sensors that rigid sensors cannot achieve.

11.
Pediatr Surg Int ; 40(1): 233, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39158792

RESUMO

PURPOSE: This study evaluates the inter-rater agreements of both the Glans-Urethral Meatus-Shaft (GMS) hypospadias score and Hypospadias Objective Penile Evaluation (HOPE) score, aiming to standardize disease classification for consistent agreement in clinically relevant characteristics of hypospadias. METHODS: Photos of hypospadias in children were collected from two separate institutions. Three raters scored the photos using GMS and HOPE, excluding penile torsion and curvature assessment in HOPE due to photo limitations. RESULTS: A total of 528 photos were included. With GMS, Fleiss' multi-rater kappa showed an agreement of 0.745 for glans-urethral plate, 0.869 for meatus, and 0.745 for shaft. For HOPE scores, the agreements were 0.888 for position of meatus, 0.669 for shape of meatus, 0.730 for shape of glans, and 0.708 for the shape of the skin. The lower agreement in the shape of the meatus evaluation may be attributed to the lack of a quantitative classification method in HOPE. Experts rely on their subjective judgment based on the provided example photos and their index patient. CONCLUSIONS: While there is high agreement among experts when evaluating hypospadias using the GMS and HOPE scoring criteria, only the position of the meatus achieved nearly perfect agreement highlighting that the current scoring systems entail a subjective element in disease classification.


Assuntos
Hipospadia , Pênis , Uretra , Humanos , Hipospadia/classificação , Masculino , Lactente , Fotografação/métodos , Pré-Escolar , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Criança
12.
Mol Carcinog ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136580

RESUMO

Gene fusions are common somatic alterations in cancers, and fusions with tumorigenic features have been identified as novel drivers of cancer and therapeutic targets. Few studies have determined whether the oncogenic ability of fusion genes is related to the induction of stemness in cells. Cancer stem cells (CSCs) are a subset of cells that contribute to cancer progression, metastasis, and recurrence, and are critical components of the aggressive features of cancer. Here, we investigated the CSC-like properties induced by CD63-BCAR4 fusion gene, previously reported as an oncogenic fusion, and its potential contribution for the enhanced metastasis as a notable characteristic of CD63-BCAR4. CD63-BCAR4 overexpression facilitates sphere formation in immortalized bronchial epithelial cells. The significantly enhanced sphere-forming activity observed in tumor-derived cells from xenografted mice of CD63-BCAR4 overexpressing cells was suppressed by silencing of BCAR4. RNA microarray analysis revealed that ALDH1A1 was upregulated in the BCAR4 fusion-overexpressing cells. Increased activity and expression of ALDH1A1 were observed in the spheres of CD63-BCAR4 overexpressing cells compared with those of the empty vector. CD133 and CD44 levels were also elevated in BCAR4 fusion-overexpressing cells. Increased NANOG, SOX2, and OCT-3/4 protein levels were observed in metastatic tumor cells derived from mice injected with CD63-BCAR4 overexpressing cells. Moreover, DEAB, an ALDH1A1 inhibitor, reduced the migration activity induced by CD63-BCAR4 as well as the sphere-forming activity. Our findings suggest that CD63-BCAR4 fusion induces CSC-like properties by upregulating ALDH1A1, which contributes to its metastatic features.

13.
Cancer Cell Int ; 24(1): 282, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135074

RESUMO

BACKGROUND: Risk stratification in multiple myeloma (MM) patients is crucial, and molecular genetic studies play a significant role in achieving this objective. Enrichment of plasma cells for next-generation sequencing (NGS) analysis has been employed to enhance detection sensitivity. However, these methods often come with limitations, such as high costs and low throughput. In this study, we explore the use of an error-corrected ultrasensitive NGS assay called positional indexing sequencing (PiSeq-MM). This assay can detect somatic mutations in MM patients without relying on plasma cell enrichment. METHOD: Diagnostic bone marrow aspirates (BMAs) and blood samples from 14 MM patients were used for exploratory and validation sets. RESULTS: PiSeq-MM successfully detected somatic mutations in all BMAs, outperforming conventional NGS using plasma cells. It also identified 38 low-frequency mutations that were missed by conventional NGS, enhancing detection sensitivity below the 5% analytical threshold. When tested in an actual clinical environment, plasma cell enrichment failed in most BMAs (14/16), but the PiSeq-MM enabled mutation detection in all BMAs. There was concordance between PiSeq-MM using BMAs and ctDNA analysis in paired blood samples. CONCLUSION: This research provides valuable insights into the genetic landscape of MM and highlights the advantages of error-corrected NGS for detecting low-frequency mutations. Although the current standard method for mutation analysis is plasma cell-enriched BMAs, total BMA or ctDNA testing with error correction is a viable alternative when plasma cell enrichment is not feasible.

14.
Future Oncol ; : 1-11, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39114870

RESUMO

WHAT IS THIS SUMMARY ABOUT?: Researchers wanted to study whether the research drug zanidatamab could help people with a type of cancer called biliary tract cancer. In some people, biliary tract cancer cells make extra copies of a gene called HER2 (also called ERBB2). This is known as being HER2-amplified. Zanidatamab is an antibody designed to destroy cancer cells that have higher-than-normal HER2 protein or gene levels. Zanidatamab is currently under research and is not yet approved for any diseases. Participants in this phase 2b clinical study had tumors that were HER2-amplified and at the advanced or metastatic stage. Participants also had cancer which had become worse after previous chemotherapy or had side effects that were too bad to continue chemotherapy. They also had to meet other requirements to be enrolled. Researchers measured the amount of HER2 protein in the tumor samples of the participants who were enrolled. There were 80 participants with tumors that were both HER2 amplified and had higher-than-normal HER2 protein amounts (considered to be 'HER2-positive'). There were 7 participants with tumors that were HER2-amplified, but had little-to-no levels of the HER2 protein (considered to be 'HER2-low'). All participants in the study were treated with zanidatamab and no other cancer treatments once every 2 weeks. WHAT ARE THE KEY TAKEAWAYS?: In the HER2-positive group, 33 of 80 (41%) participants had their tumors shrink by 30% or more of their original size. In half of these participants, their tumors did not grow for 13 months or longer. No participant in the HER2-low group had their tumors shrink by 30% or more. In total, 63 of 87 participants (72%) had at least one side effect believed to be related to zanidatamab treatment. Most side effects were mild or moderate in severity. No participant died from complications related to zanidatamab. Diarrhea was one of the more common side effects and was experienced by 32 of 87 participants (37%). Side effects related to receiving zanidatamab through the vein, such as chills, fever, or high blood pressure, were experienced by 29 of 87 participants (33%). WHAT ARE THE CONCLUSIONS REPORTED BY THE RESEARCHERS?: The results of this study support the potential for zanidatamab as a new therapy for people with HER2-positive biliary tract cancer after they had already received chemotherapy. More research is occurring to support these results.Clinical Trial Registration: NCT04466891 (HERIZON-BTC-01 study).


The HERIZON-BTC-01 study revealed zanidatamab as a potentially effective treatment for HER2-positive biliary tract cancer after standard chemotherapy fails. Read more in the lay summary by @hardingjjmd, @DrShubhamPant, and coauthors. #BiliaryTractCancer #HER2 #zanidatamab.

15.
Cancer Rep (Hoboken) ; 7(8): e2155, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39118235

RESUMO

OBJECTIVES: In ovarian and other cancers, low muscle mass and density are associated with poorer clinical outcomes. However, screening for cancer-related sarcopenia (typically defined as low muscle mass) is not routinely conducted. The European Working Group on Sarcopenia in Older People (EWGSOP) recommends an algorithm for sarcopenia screening and diagnosis in clinical settings, with sarcopenia based on muscle strength and mass, and severity on physical performance. We explored the application of the EWGSOP2 algorithm to assess sarcopenia in six ovarian cancer patients receiving neoadjuvant chemotherapy. METHODS: We assessed sarcopenia risk with the SARC-F screening questionnaire (at risk ≥4 points), muscle strength with a handgrip strength test (cut point <16 kg) and five times sit-to-stand test (cut point >15 s), muscle mass by skeletal muscle index (SMI in cm2/m2 from a single computed tomography [CT] image; cut point <38.5 cm2/m2), and physical performance with a 4-m gait speed test (cut point ≤0.8 m/s). RESULTS: Of six participants, none were identified as "at risk" for sarcopenia based on SARC-F scores. Two participants were severely sarcopenic based on EWGSOP2 criteria (had low muscle strength, mass, and physical performance), and five participants were sarcopenic based on muscle mass only. DISCUSSION: Ovarian cancer patients with low muscle mass during neoadjuvant chemotherapy may not be identified as sarcopenic based on the EWGSOP2 diagnostic algorithm. While lacking a universally accepted definition for cancer-related sarcopenia and cancer-specific recommendations for the screening, diagnosis, and treatment of sarcopenia, ovarian cancer clinicians should focus on the diagnosis and treatment of low muscle mass and density.


Assuntos
Terapia Neoadjuvante , Neoplasias Ovarianas , Sarcopenia , Humanos , Feminino , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Sarcopenia/induzido quimicamente , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Idoso , Pessoa de Meia-Idade , Força da Mão , Força Muscular , Músculo Esquelético/patologia , Algoritmos , Quimioterapia Adjuvante/efeitos adversos , Estadiamento de Neoplasias
16.
Int J Surg ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39116448

RESUMO

BACKGROUND: Accurate forecasting of clinical outcomes after kidney transplantation is essential for improving patient care and increasing the success rates of transplants. Our study employs advanced machine learning (ML) algorithms to identify crucial prognostic indicators for kidney transplantation. By analyzing complex datasets with ML models, we aim to enhance prediction accuracy and provide valuable insights to support clinical decision-making. MATERIALS AND METHODS: Analyzing data from 4077 KT patients (June 1990 - May 2015) at a single center, this research included 27 features encompassing recipient/donor traits and peri-transplant data. The dataset was divided into training (80%) and testing (20%) sets. Four ML models-eXtreme Gradient Boosting (XGBoost), Feedforward Neural Network, Logistic Regression, and Support Vector Machine-were trained on carefully selected features to predict the success of graft survival. Performance was assessed by precision, sensitivity, F1 score, Area Under the Receiver Operating Characteristic (AUROC), and Area Under the Precision-Recall Curve. RESULTS: XGBoost emerged as the best model, with an AUROC of 0.828, identifying key survival predictors like T-cell flow crossmatch positivity, creatinine levels two years post-transplant and human leukocyte antigen mismatch. The study also examined the prognostic importance of histological features identified by the Banff criteria for renal biopsy, emphasizing the significance of intimal arteritis, interstitial inflammation, and chronic glomerulopathy. CONCLUSION: The study developed ML models that pinpoint clinical factors crucial for KT graft survival, aiding clinicians in making informed post-transplant care decisions. Incorporating these findings with the Banff classification could improve renal pathology diagnosis and treatment, offering a data-driven approach to prioritizing pathology scores.

17.
Int J Surg ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39116451

RESUMO

BACKGROUND: The increasing use of kidneys from elderly donors raises concerns due to age-related nephron loss. Combined with nephrectomy, this loss of nephrons markedly increases the risk of developing chronic kidney disease (CKD). This study aimed to investigate the prognostic value of preoperative kidney cortex volume in predicting the loss of kidney function in elderly donors, by developing an artificial intelligence (AI)-based model for precise kidney volume measurement and applying it to living kidney donors. MATERIALS METHODS: A multicenter retrospective cohort study using data from living donors who underwent donor nephrectomy between January 2010 and December 2020 was conducted. An AI segmentation model was developed and validated to measure kidney cortex volume from pre-donation computer tomographic (CT) images. The association between measured preoperative kidney volumes and post-nephrectomy renal function was analyzed through a generalized additive model. RESULTS: A total of 1074 living kidney donors were included in the study. Validation of the developed kidney cortex volume model showed a Dice similarity coefficient of 0.97 and a Hausdorff distance of 0.76 mm. The measured cortex volumes exhibited an age-related decrease, which correlated with declining kidney function. Elderly donors showed greater decreases in estimated glomerular filtration rates (eGFR) post-donation compared to young donors (P=0.041). Larger preoperative remnant kidney cortex volume was associated with significantly less decline of eGFR post-donation than those with smaller preoperative remnant kidney cortex volume (P<0.001). CONCLUSION: This study highlights the critical role of preoperative kidney cortex volume in the donor assessment process, particularly for elderly donors. The fully automated model for measuring kidney cortex volume provides a valuable tool for predicting post-donation renal function and holds promise for enhancing donor evaluation and safety.

18.
World J Emerg Surg ; 19(1): 27, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090705

RESUMO

BACKGROUND: No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment. METHODS: This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26). RESULTS: Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p < 0.001, respectively). Conversely, initial heart rate and body temperature were significantly lower in group 2 (92.5 ± 21.0 vs. 109.0 ± 28.1 beat/min, p < 0.001, and 37.3 ± 0.8 °C vs. 37.0 ± 0.9 °C, p = 0.011, respectively). Logistic regression analysis identified low initial body temperature, high lactic acid level, and shock index as independent predictors of surgical intervention (p = 0.029, p = 0.027, and p = 0.049, respectively). Regarding the causes of PPH, tone was significantly more prevalent in group 1 (57.2% vs. 35.2%, p = 0.002), whereas trauma was significantly more prevalent in group 2 (24.5% vs. 39.4%, p = 0.030). Group 2 had worse overall outcomes and prognoses than group 1. The subgroup analysis showed significantly higher rates of uterine atony combined with other causes, hysterectomy, and disseminated intravascular coagulopathy in the delayed surgical intervention group than the immediate surgical intervention group (42.2% vs. 69.2%, p = 0.027; 51.1% vs. 73.1%, p = 0.049; and 17.8% vs. 46.2%, p = 0.018, respectively). CONCLUSIONS: Patients with PPH presenting with increased lactic acid levels and shock index and decreased body temperature may be surgical candidates. Additionally, immediate surgical intervention in patients with uterine atony combined with other causes of PPH could improve prognosis and reduce postoperative complications.


Assuntos
Hemorragia Pós-Parto , Humanos , Feminino , Estudos Retrospectivos , Adulto , Prognóstico , Gravidez , Ácido Láctico/sangue
19.
J Pediatr Urol ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39089950

RESUMO

INTRODUCTION: Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are structural disorders originating prenatally and present at birth. Affecting 4.2 to 1000 per 10,000 births globally, CAKUT includes conditions like posterior urethral valves, cloacal anomalies, and reflux nephropathy. These anomalies can lead to chronic kidney disease (CKD) or end-stage kidney disease (ESKD) in children, necessitating renal replacement therapy or transplantation. OBJECTIVES: This article aims to provide an updated perspective on pediatric kidney transplantation for children with CAKUT, emphasizing pre-transplant evaluation and management to optimize long-term outcomes. METHODS: A comprehensive urologic evaluation is essential for children with ESKD being considered for kidney transplantation. Key pre-transplant investigations include kidney/bladder ultrasound (US), voiding cystourethrogram (VCUG), uroflowmetry, and urodynamics (UDS)/video-urodynamics (VUDS). Non-operative interventions such as pharmacotherapy and clean intermittent catheterization (CIC) are also considered. Surgical interventions, like augmentation cystoplasty or continent catheterizable channels, are evaluated based on individual patient needs. RESULTS: Kidney/bladder US and VCUG provide essential anatomical information. UDS offers comprehensive functional data, identifying hostile bladders needing pre-transplant optimization. Non-surgical measures like anticholinergics and CIC improve bladder function, while surgical options enhance compliance and capacity. Concurrent interventions during transplantation are feasible but require careful consideration of risks and benefits. DISCUSSION: Children with CAKUT undergoing kidney transplantation exhibit comparable or better graft survival rates than those without CAKUT. However, those with lower urinary tract obstructions (LUTO) may have poorer long-term outcomes. UDS is crucial for evaluating bladder function pre-transplant, guiding the need for interventions. Long-term monitoring for urinary tract infections (UTIs) and bladder dysfunction is essential. CONCLUSION: Optimal outcomes in pediatric kidney transplantation for CAKUT patients require thorough pre-transplant evaluation and management, particularly for those with LUTO. Multidisciplinary approaches ensure careful monitoring and timely interventions, improving graft survival and quality of life for these patients.

20.
Eur J Anaesthesiol ; 41(9): 687-694, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087414

RESUMO

BACKGROUND: Hypoxaemia occurs frequently during paediatric laryngeal microsurgery. OBJECTIVE: The oxygen reserve index is a noninvasive and continuous parameter to assess PaO2 levels in the range of 100 to 200 mmHg. It ranges from 0 to 1.0. We investigated whether monitoring the oxygen reserve index can reduce the incidence of SpO2 90% or less. DESIGN: Randomised controlled trial. SETTING: A tertiary care paediatric hospital. PARTICIPANTS: Paediatric patients aged 18 years or less scheduled to undergo laryngeal microsurgery. INTERVENTION: The patients were randomly allocated to the oxygen reserve index or control groups, and stratified based on the presence of a tracheostomy tube. Rescue intervention was performed when the oxygen reserve index was 0.2 or less and the SpO2 was 94% or less in the oxygen reserve index and control groups, respectively. MAIN OUTCOME MEASURE: The primary outcome was the incidence of SpO2 90% or less during the surgery. RESULTS: Data from 88 patients were analysed. The incidence of SpO2 ≤ 90% did not differ between the oxygen reserve index and control groups [P = 0.114; 11/44, 25% vs. 18/44, 40.9%; relative risk: 1.27; and 95% confidence interval (CI): 0.94 to 1.72]. Among the 128 rescue interventions, SpO2 ≤ 90% event developed in 18 out of 75 events (24%) and 42 out of 53 events (79.2%) in the oxygen reserve index and control groups, respectively (P < 0.001; difference: 55.2%; and 95% CI 38.5 to 67.2%). The number of SpO2 ≤ 90% events per patient in the oxygen reserve index group (median 0, maximum 3) was less than that in the control group (median 0, maximum 8, P = 0.031). CONCLUSION: Additional monitoring of the oxygen reserve index, with a target value of greater than 0.2 during paediatric airway surgery, alongside peripheral oxygen saturation, did not reduce the incidence of SpO2 ≤ 90%.


Assuntos
Hipóxia , Saturação de Oxigênio , Humanos , Masculino , Feminino , Hipóxia/prevenção & controle , Hipóxia/sangue , Hipóxia/etiologia , Pré-Escolar , Oxigênio/sangue , Criança , Lactente , Microcirurgia/métodos , Laringe , Oximetria/métodos , Monitorização Intraoperatória/métodos , Adolescente
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