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1.
Head Neck Pathol ; 18(1): 64, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958850

RESUMO

PURPOSE: There are a number of diagnostic criteria that can be used to support a diagnosis of Sjögren's syndrome (SS), a chronic autoimmune condition often characterised by xerostomia and xerophthalmia. Of the available investigations, the most invasive is the labial gland biopsy (LGB) for histopathology, which is associated with a risk of long-term altered sensation to the lip. A positive histological diagnosis is currently considered to be one of the most objective criteria, however there is debate about the interobserver agreement between pathologists, as well as the sensitivity and specificity of this test. We aim to determine if the diagnostic value of the LGB is significant enough to warrant the surgical procedure and its associated risks. METHODS: This study involved assessing the degree of agreement between members of a pathology team for a cohort of 50 LGBs taken for the purpose of confirming or excluding SS. The Tarpley system was used, which involves the allocation of a 'focus score'. Additionally, the histological diagnoses were compared to the relevant serological findings where available. RESULTS: All cases within the cohort had adequate tissue for assessment. 84% agreement (Cohen's Kappa = 0.585) was seen between the current team's consensus and the original reporting pathologist on whether the appearance was supportive of SS. However, only 58% agreement was seen for focus scores (Weighted Kappa = 0.496). The agreement between the serology result and whether the histology was supportive of SS was 79% (Cohen's Kappa = 0.493). CONCLUSION: The findings raise the possibility that undue emphasis is placed on the value of a histological SS diagnosis. The current system for assessing and grading these biopsies is ambiguous in nature, with a low threshold considered indicative of SS. Due to the risk of complications associated with a LGB, alternative minimally invasive investigations should always be considered. The histological findings in isolation, particularly when a low focus score is seen, may not be predictive of a diagnosis of SS.


Assuntos
Glândulas Salivares Menores , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/patologia , Biópsia , Glândulas Salivares Menores/patologia , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Masculino , Sensibilidade e Especificidade
2.
Front Neurol ; 15: 1420530, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978812

RESUMO

Background: The recommended treatment for cervical spinal cord injury (cSCI) is surgical decompression and stabilization within 24 h after injury. The aims of the study were to estimate our institutional compliance with this recommendation and identify potential factors associated with surgical delay. Methods: Population-based retrospective database study of patients operated for cSCI in 2015-2022 within the South-East Norway Health Region (3.1 million inhabitants). Data extracted were demographics, injury description, management timeline, place of primary triage [local hospital (LH) or neurotrauma center (NTC)]. Main outcome variables were: (1) time from injury to surgery at NTC, (2) time from injury to admission NTC, and (3) time from admission NTC to surgery. Results: We found 243 cSCI patients having acute neck surgery. Their median age was 63 years (IQR 47-74 years), 77% were male, 48% were ≥65 years old. Primary triage at an LH occurred in 150/243 (62%). The median time from injury to acute surgery was 27.8 h (IQR 15.4-61.9 h), and 47% had surgery within 24 h. The median time from injury to NTC admission was 5.6 h (IQR 1.9-19.4 h), and 67% of the patients were admitted to the NTC within 12 h. Significant factors associated with increased time from injury to NTC admission were transfer via LH, severe preinjury comorbidities, less severe cSCI, time of injury other than night, absence of multiple injuries. The median time from NTC admission to surgery was 16.7 h (IQR 9.5-31.0 h), and 70% had surgery within 24 h. Significant factors associated with increased time from NTC admission to surgery were increasing age and non-translational injury morphology. Conclusion: Less than half of the patients with cSCI were operated on within the recommended 24 h time frame after injury. To increase the fraction of early surgery, we suggest the following: (1) patients with clinical suspicion of cSCI should be transported directly to the NTC from the scene of the accident, (2) MRI should be performed only at the NTC, (3) at the NTC, surgery should commence on the same calendar day as arrival or as the first operation the following day.

3.
Ann Vasc Surg ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39004279

RESUMO

OBJECTIVES: Phlebolymphedema is a challenging condition to manage, with limited options for effective treatment. For patients, this may be debilitating and lead to infection, loss of independence and affect quality of life (QOL). This study aims to evaluate patient-reported outcomes of an advanced pneumatic compression device (APCD) in the treatment of lower extremity phlebolymphedema. METHODS: Patients with diagnosis of lower extremity phlebolymphedema at an acute care facility within the New York City Health and Hospitals Cooperation treated with the Flexitouch (FLX; Tactile Systems Technology, Inc, Minneapolis, Minnesota) APCD from December 2021 to March 2023 were evaluated. Patient-perceived subjective outcomes were assessed via a short questionnaire, with subsequent analysis using Chi-squared test. Primary endpoints were subjective improvements in 1) swelling, 2) pain, and 3) ease of use of device as surrogates for patient satisfaction. Secondary endpoint was subjective patient-reported compliance, obtained by investigating 1) if patients were trained to use device, and 2) if patients were using the device. RESULTS: A total of 52 participants were included in this study, consisting of 30.8% male and 69.2% female patients with a mean age of 71.7 years. While selection criteria did not exclude unilateral disease or alternative etiologies, we note that the entire study population had been diagnosed with bilateral lower extremity lymphedema in the setting of chronic venous insufficiency. Other patient characteristics including race, comorbidities and smoking status were documented in Table 1. Table 2 demonstrates the results of Chi-squared analysis. This study noted significant patient-perceived improvement in swelling and pain (91.4% with P < 0.00001; 85.7% with P = 0.00002 respectively) as well as patient-reported ease of use of the FLX device (85.7% with P = 0.00002). Additional secondary findings included a majority of patients reporting being trained on how to use FLX and also maintaining compliance with the device (69.2% with P = 0.005; 67.3% with P = 0.012 respectively). CONCLUSIONS: FLX APCD use has been found to demonstrate desirable patient-reported outcomes as a general trend. The participants in this study noted statistically significant subjective improvement in swelling and pain, ease of use of device as well as adherence to training and compliance with device. FLX appears to be positively received by patients, and the authors recommend its consideration for management of bilateral lower extremity phlebolymphedema.

4.
Medicina (Kaunas) ; 60(6)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38929573

RESUMO

Background and Objectives: Large language models (LLMs) are emerging as valuable tools in plastic surgery, potentially reducing surgeons' cognitive loads and improving patients' outcomes. This study aimed to assess and compare the current state of the two most common and readily available LLMs, Open AI's ChatGPT-4 and Google's Gemini Pro (1.0 Pro), in providing intraoperative decision support in plastic and reconstructive surgery procedures. Materials and Methods: We presented each LLM with 32 independent intraoperative scenarios spanning 5 procedures. We utilized a 5-point and a 3-point Likert scale for medical accuracy and relevance, respectively. We determined the readability of the responses using the Flesch-Kincaid Grade Level (FKGL) and Flesch Reading Ease (FRE) score. Additionally, we measured the models' response time. We compared the performance using the Mann-Whitney U test and Student's t-test. Results: ChatGPT-4 significantly outperformed Gemini in providing accurate (3.59 ± 0.84 vs. 3.13 ± 0.83, p-value = 0.022) and relevant (2.28 ± 0.77 vs. 1.88 ± 0.83, p-value = 0.032) responses. Alternatively, Gemini provided more concise and readable responses, with an average FKGL (12.80 ± 1.56) significantly lower than ChatGPT-4's (15.00 ± 1.89) (p < 0.0001). However, there was no difference in the FRE scores (p = 0.174). Moreover, Gemini's average response time was significantly faster (8.15 ± 1.42 s) than ChatGPT'-4's (13.70 ± 2.87 s) (p < 0.0001). Conclusions: Although ChatGPT-4 provided more accurate and relevant responses, both models demonstrated potential as intraoperative tools. Nevertheless, their performance inconsistency across the different procedures underscores the need for further training and optimization to ensure their reliability as intraoperative decision-support tools.


Assuntos
Cirurgia Plástica , Humanos , Cirurgia Plástica/métodos , Idioma , Procedimentos de Cirurgia Plástica/métodos , Sistemas de Apoio a Decisões Clínicas
5.
J Pers Med ; 14(6)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38929832

RESUMO

In the U.S., diagnostic errors are common across various healthcare settings due to factors like complex procedures and multiple healthcare providers, often exacerbated by inadequate initial evaluations. This study explores the role of Large Language Models (LLMs), specifically OpenAI's ChatGPT-4 and Google Gemini, in improving emergency decision-making in plastic and reconstructive surgery by evaluating their effectiveness both with and without physical examination data. Thirty medical vignettes covering emergency conditions such as fractures and nerve injuries were used to assess the diagnostic and management responses of the models. These responses were evaluated by medical professionals against established clinical guidelines, using statistical analyses including the Wilcoxon rank-sum test. Results showed that ChatGPT-4 consistently outperformed Gemini in both diagnosis and management, irrespective of the presence of physical examination data, though no significant differences were noted within each model's performance across different data scenarios. Conclusively, while ChatGPT-4 demonstrates superior accuracy and management capabilities, the addition of physical examination data, though enhancing response detail, did not significantly surpass traditional medical resources. This underscores the utility of AI in supporting clinical decision-making, particularly in scenarios with limited data, suggesting its role as a complement to, rather than a replacement for, comprehensive clinical evaluation and expertise.

6.
Sci Rep ; 14(1): 14573, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38914649

RESUMO

The concept of functional localization within the brain and the associated risk of resecting these areas during removal of infiltrating tumors, such as diffuse gliomas, are well established in neurosurgery. Global efficiency (GE) is a graph theory concept that can be used to simulate connectome disruption following tumor resection. Structural connectivity graphs were created from diffusion tractography obtained from the brains of 80 healthy adults. These graphs were then used to simulate parcellation resection in every gross anatomical region of the cerebrum by identifying every possible combination of adjacent nodes in a graph and then measuring the drop in GE following nodal deletion. Progressive removal of brain parcellations led to patterns of GE decline that were reasonably predictable but had inter-subject differences. Additionally, as expected, there were deletion of some nodes that were worse than others. However, in each lobe examined in every subject, some deletion combinations were worse for GE than removing a greater number of nodes in a different region of the brain. Among certain patients, patterns of common nodes which exhibited worst GE upon removal were identified as "connectotypes". Given some evidence in the literature linking GE to certain aspects of neuro-cognitive abilities, investigating these connectotypes could potentially mitigate the impact of brain surgery on cognition.


Assuntos
Encéfalo , Imagem de Tensor de Difusão , Humanos , Masculino , Feminino , Adulto , Encéfalo/cirurgia , Encéfalo/diagnóstico por imagem , Conectoma , Pessoa de Meia-Idade , Neoplasias Encefálicas/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-38866214

RESUMO

PURPOSE: Primary soft tissue sarcoma (STS) is rare, with many tumors occurring in extremities. Local management is limb-sparing surgery and preoperative/postoperative radiation therapy (RT) for patients at high risk of local recurrence. We prospectively investigated late normal tissue toxicity and limb function observed after intensity modulated RT (IMRT) in extremity STS. METHODS AND MATERIALS: Patients with extremity STS, age ≥16 years. Two treatment cohorts: IMRT 50 Gy in 25 × 2 Gy fractions (preoperative) or 60/66 Gy in 30/33 × 2 Gy fractions (postoperative). The primary endpoint was the rate of grade ≥2 late soft tissue fibrosis (subcutaneous tissue) at 24 months after IMRT (Radiation Therapy Oncology Group late radiation morbidity scoring). RESULTS: One hundred sixty-eight patients were registered between March 2016 and July 2017. Of those, 159 (95%) received IMRT (106, 67% preoperative RT; and 53, 33% postoperative RT) with a median follow-up of 35.2 months (IQR, 32.9-36.6); 62% men, median age 58 years. Of 111 patients assessable for the primary endpoint at 24 months, 12 (10.8%; 95% CI, 5.7%-18.1%) had grade ≥2 subcutaneous fibrosis. The overall rate at 24 months of Radiation Therapy Oncology Group late skin, bone, and joint toxicity was 7 of 112 (6.3%), 3 of 112 (2.7%), and 10 of 113 (8.8%), respectively, and for Stern's scale edema was 6 of 113 (5.3%). More wound complications were observed with preoperative than postoperative RT (29.2% vs 3.8%). Overall survival at 24 months was 84.6%, and the local recurrence event rate at 24 months was 10%. CONCLUSIONS: The rate of grade ≥2 subcutaneous fibrosis at 24 months after IMRT was 10.8%, consistent with other recent trials of IMRT and lower than historically reported rates in patients treated with 3-dimensional conformal RT. This trial provides further evidence for the benefits of IMRT in this patient population.

8.
Urology ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38830555

RESUMO

OBJECTIVE: To evaluate outcomes in cancer patients with ureteral obstruction by comparison of retrograde stenting and percutaneous nephrostomy techniques. METHODS: Systematic review of all studies up to October 2023. Studies were identified from all major databases including MEDLINE, Cochrane, and EMBASE. All comparative studies between retrograde stenting and percutaneous nephrostomy were searched; studies with paediatric populations were excluded. Primary outcomes were procedure and intervention failure rates; secondary outcomes were infection, blockage, displacement, and unplanned exchange rates along with procedure time and length of stay. RESULTS: Eighteen studies with 1228 patients contributed to the summative outcome. Percutaneous nephrostomy was statistically superior to retrograde stenting for procedure failure rate (P <.00001) and intervention failure rate (P =.0004). Retrograde stenting was statistically superior to percutaneous nephrostomy for displacement rates (P = .003), procedure time (P <.00001), and length of stay (P <.00001). Retrograde stenting showed no difference to percutaneous nephrostomy for infection rates (P = .94), blockage rates (P = .93), unplanned exchange rates (P = .48), CONCLUSION: There is no absolute superiority for retrograde stenting or percutaneous nephrostomy for malignant ureteral obstruction. Both techniques have their advantages and disadvantages, with some comparable outcomes; patients are key when selecting the best technique. Larger studies are required to assess the outcomes of both techniques.

9.
Healthcare (Basel) ; 12(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891158

RESUMO

Since their release, the medical community has been actively exploring large language models' (LLMs) capabilities, which show promise in providing accurate medical knowledge. One potential application is as a patient resource. This study analyzes and compares the ability of the currently available LLMs, ChatGPT-3.5, GPT-4, and Gemini, to provide postoperative care recommendations to plastic surgery patients. We presented each model with 32 questions addressing common patient concerns after surgical cosmetic procedures and evaluated the medical accuracy, readability, understandability, and actionability of the models' responses. The three LLMs provided equally accurate information, with GPT-3.5 averaging the highest on the Likert scale (LS) (4.18 ± 0.93) (p = 0.849), while Gemini provided significantly more readable (p = 0.001) and understandable responses (p = 0.014; p = 0.001). There was no difference in the actionability of the models' responses (p = 0.830). Although LLMs have shown their potential as adjunctive tools in postoperative patient care, further refinement and research are imperative to enable their evolution into comprehensive standalone resources.

10.
NPJ Precis Oncol ; 8(1): 137, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942998

RESUMO

Oral epithelial dysplasia (OED) is a premalignant histopathological diagnosis given to lesions of the oral cavity. Its grading suffers from significant inter-/intra-observer variability, and does not reliably predict malignancy progression, potentially leading to suboptimal treatment decisions. To address this, we developed an artificial intelligence (AI) algorithm, that assigns an Oral Malignant Transformation (OMT) risk score based on the Haematoxylin and Eosin (H&E) stained whole slide images (WSIs). Our AI pipeline leverages an in-house segmentation model to detect and segment both nuclei and epithelium. Subsequently, a shallow neural network utilises interpretable morphological and spatial features, emulating histological markers, to predict progression. We conducted internal cross-validation on our development cohort (Sheffield; n = 193 cases) and independent validation on two external cohorts (Birmingham and Belfast; n = 89 cases). On external validation, the proposed OMTscore achieved an AUROC = 0.75 (Recall = 0.92) in predicting OED progression, outperforming other grading systems (Binary: AUROC = 0.72, Recall = 0.85). Survival analyses showed the prognostic value of our OMTscore (C-index = 0.60, p = 0.02), compared to WHO (C-index = 0.64, p = 0.003) and binary grades (C-index = 0.65, p < 0.001). Nuclear analyses elucidated the presence of peri-epithelial and intra-epithelial lymphocytes in highly predictive patches of transforming cases (p < 0.001). This is the first study to propose a completely automated, explainable, and externally validated algorithm for predicting OED transformation. Our algorithm shows comparable-to-human-level performance, offering a promising solution to the challenges of grading OED in routine clinical practice.

11.
ACS Omega ; 9(24): 26540-26548, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38911793

RESUMO

Bio-oil production from rice husk, an abundant agricultural residue, has gained significant attention as a sustainable and renewable energy source. The current research aims to employ artificial neural network (ANN) and support vector machine (SVM) modeling techniques for the optimization of operating parameters for bio-oil extracted from rice husk ash (RHA) through pyrolysis. ANN and SVM methods are employed to model and optimize the operational conditions, including temperature, heating rate, and feedstock particle size, to enhance the yield and quality of bio-oil. Additionally, ANN modeling is utilized to create a predictive model for bio-oil properties, allowing for the efficient optimization of pyrolysis conditions. This research provides valuable insights into the production and properties of bio-oil from RHA. By harnessing the capabilities of ANN and SVM, this research not only aids in understanding the intricate relationships between process variables and bio-oil properties but also provides a means to systematically enhance the production process. The predictive results obtained from the ANN were found to be good when compared with the SVM. Several models with different numbers of neurons have been trained with different transfer functions. R values for the training, validation, and test phases are around 1.0, i.e., 0.9981, 0.9976, and 0.9978, respectively. The overall R-value was 0.9960 for the proposed network. The findings were considered acceptable, as the overall R-value was close to 1.0. The optimized operational parameters contribute to the efficient conversion of RHA into bio-oil, thereby promoting the use of this sustainable resource for renewable energy production. This approach aligns with the growing emphasis on reducing the environmental impact of traditional fossil fuels and advancing the utilization of alternative and environmentally friendly energy sources.

12.
J Clin Med ; 13(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38792374

RESUMO

Background: OpenAI's ChatGPT (San Francisco, CA, USA) and Google's Gemini (Mountain View, CA, USA) are two large language models that show promise in improving and expediting medical decision making in hand surgery. Evaluating the applications of these models within the field of hand surgery is warranted. This study aims to evaluate ChatGPT-4 and Gemini in classifying hand injuries and recommending treatment. Methods: Gemini and ChatGPT were given 68 fictionalized clinical vignettes of hand injuries twice. The models were asked to use a specific classification system and recommend surgical or nonsurgical treatment. Classifications were scored based on correctness. Results were analyzed using descriptive statistics, a paired two-tailed t-test, and sensitivity testing. Results: Gemini, correctly classifying 70.6% hand injuries, demonstrated superior classification ability over ChatGPT (mean score 1.46 vs. 0.87, p-value < 0.001). For management, ChatGPT demonstrated higher sensitivity in recommending surgical intervention compared to Gemini (98.0% vs. 88.8%), but lower specificity (68.4% vs. 94.7%). When compared to ChatGPT, Gemini demonstrated greater response replicability. Conclusions: Large language models like ChatGPT and Gemini show promise in assisting medical decision making, particularly in hand surgery, with Gemini generally outperforming ChatGPT. These findings emphasize the importance of considering the strengths and limitations of different models when integrating them into clinical practice.

13.
Acta Radiol ; : 2841851241249161, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38751050

RESUMO

BACKGROUND: Advances in molecular imaging strategies have had an effect on precise diagnosis and treatment. Research has been intensified to develop more effective and versatile radiopharmaceuticals to uplift diagnostic efficiency and, consequently, the treatment. PURPOSE: To label the flutamide (FLUT) coupled with diethylenetriamine pentaacetate (DTPA) with technetium-99 m (99mTc) and to evaluate its binding efficiency with rhabdomyosarcoma (RMS) cancer cells. MATERIAL AND METHODS: Radiolabeling of FLUT with 185 MBq freshly eluted 99mTcO4-1 was carried out via DTPA bifunctional chelating agent using stannous chloride reducing agent at pH 5. The labeled compound was assessed for its purity using chromatography analysis, stability in saline and blood serum, AND charge using paper electrophoresis. Normal biodistribution was studied using a mouse model, while binding affinity with RMS cancer cells was studied using an internalization assay. The in vivo accumulation of RMS cancer cells in a rabbit model was monitored using a SPECT gamma camera. RESULTS: Radiolabeling reaction displayed a pharmaceutical yield of 97% and a stability assay showed >95% intact radiopharmaceutical up to 6 h in saline and blood serum. In vitro internalization studies showed the potential of [99mTc]DTPA-FLUT to enter into cancer cells. This biodistribution study showed rapid blood clearance and minimum uptake by body organs, and scintigraphy displayed the [99mTc]DTPA-FLUT uptake by lesion, induced by RMS cancer cell lines in rabbit. CONCLUSION: Stable, newly developed [99mTc]DTPA-FLUT seeks its way to internalize into RMS cancer cells, indicating it could be a potential candidate for the diagnosis of RMS cancer.

15.
Imaging Sci Dent ; 54(1): 109-113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38571770

RESUMO

A 54-year-old male patient presented for a periodic check-up at the dental clinic. A panoramic radiograph showed bilateral ossification of the stylohyoid ligament with an oval radiopacity on the right side. Cone-beam computed tomography revealed a well-defined, homogenous hyperdense entity from the lower third of the ossified stylohyoid ligament on the right side. The differential diagnosis of osteoma on the stylohyoid chain includes Eagle syndrome and benign tumors of the stylohyoid chain and adjacent structures. Osteoma rarely manifests in the neck. Even more infrequent are tumors originating from the stylohyoid chain, with only a single documented case of osteoma reported in the literature in 1993. Due to the asymptomatic status, no surgical intervention was advised, and the case would be monitored periodically. This case report describes the details of an osteoma that emerged from the stylohyoid chain, marking it as the second recorded occurrence of this highly rare condition.

16.
Eplasty ; 24: QA3, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38501142
17.
Kidney Int ; 106(1): 115-125, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38521406

RESUMO

Cardiovascular disease, infection, malignancy, and thromboembolism are major causes of morbidity and mortality in kidney transplant recipients (KTR). Prospectively identifying monogenic conditions associated with post-transplant complications may enable personalized management. Therefore, we developed a transplant morbidity panel (355 genes) associated with major post-transplant complications including cardiometabolic disorders, immunodeficiency, malignancy, and thrombophilia. This gene panel was then evaluated using exome sequencing data from 1590 KTR. Additionally, genes associated with monogenic kidney and genitourinary disorders along with American College of Medical Genetics (ACMG) secondary findings v3.2 were annotated. Altogether, diagnostic variants in 37 genes associated with Mendelian kidney and genitourinary disorders were detected in 9.9% (158/1590) of KTR; 25.9% (41/158) had not been clinically diagnosed. Moreover, the transplant morbidity gene panel detected diagnostic variants for 56 monogenic disorders in 9.1% KTRs (144/1590). Cardiovascular disease, malignancy, immunodeficiency, and thrombophilia variants were detected in 5.1% (81), 2.1% (34), 1.8% (29) and 0.2% (3) among 1590 KTRs, respectively. Concordant phenotypes were present in half of these cases. Reviewing implications for transplant care, these genetic findings would have allowed physicians to set specific risk factor targets in 6.3% (9/144), arrange intensive surveillance in 97.2% (140/144), utilize preventive measures in 13.2% (19/144), guide disease-specific therapy in 63.9% (92/144), initiate specialty referral in 90.3% (130/144) and alter immunosuppression in 56.9% (82/144). Thus, beyond diagnostic testing for kidney disorders, sequence annotation identified monogenic disorders associated with common post-transplant complications in 9.1% of KTR, with important clinical implications. Incorporating genetic diagnostics for transplant morbidities would enable personalized management in pre- and post-transplant care.


Assuntos
Sequenciamento do Exoma , Testes Genéticos , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Testes Genéticos/métodos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Complicações Pós-Operatórias/genética , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Transplantados/estatística & dados numéricos , Idoso , Predisposição Genética para Doença
18.
bioRxiv ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38405969

RESUMO

Schistosomiasis, or bilharzia, is a neglected tropical disease caused by Schistosoma spp. blood flukes that infects over 200 million people worldwide. Just one partially effective drug is available, and new drugs and drug targets would be welcome. The 20S proteasome is a validated drug target for many parasitic infections, including those caused by Plasmodium and Leishmania. We previously showed that anticancer proteasome inhibitors that act through the Schistosoma mansoni 20S proteasome (Sm20S) kill the parasite in vitro. To advance these initial findings, we employed Multiplex Substrate Profiling by Mass Spectrometry (MSP-MS) to define the substrate cleavage specificities of the three catalytic ß subunits of purified Sm20S. The profiles in turn were used to design and synthesize subunit-specific optimized substrates that performed two to eight fold better than the equivalent substrates used to measure the activity of the constitutive human proteasome (c20S). These specific substrates also eliminated the need to purify Sm20S from parasite extracts - a single step enrichment was sufficient to accurately measure substrate hydrolysis and its inhibition with proteasome inhibitors. Finally, we show that the substrate and inhibition profiles for the 20S proteasome from the three medically important schistosome species are similar, suggesting that data arising from an inhibitor development campaign that focuses on Sm20S can be extrapolated to the other two targets with consequent time and cost savings.

19.
Artif Organs ; 48(6): 675-682, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38321771

RESUMO

INTRODUCTION: For the Veterans Health Administration (VHA) to continue to perform complex cardiothoracic surgery, there must be an established pathway for providing urgent/emergent extracorporeal life support (ECLS). Partnership with a nearby tertiary care center with such expertise may be the most resource-efficient way to provide ECLS services to patients in post-cardiotomy cardiogenic shock or respiratory failure. The goal of this project was to assess the efficiency, safety, and outcomes of surgical patients who required transfer for perioperative ECLS from a single stand-alone Veterans Affairs Medical Center (VAMC) to a separate ECLS center. METHODS: Cohort consisted of all cardiothoracic surgery patients who experienced cardiogenic shock or refractory respiratory failure at the local VAMC requiring urgent or emergent institution of ECLS between 2019 and 2022. The primary outcomes are the safety and timeliness of transport. RESULTS: Mean time from the initial shock call to arrival at the ECLS center was 2.8 h. There were no complications during transfer. Six patients (86%) survived to decannulation. CONCLUSION: These results suggest that complex cardiothoracic surgery can be performed within the VHA system and when there is an indication for ECLS, those services can be safely and effectively provided at an affiliated, properly equipped center.


Assuntos
Oxigenação por Membrana Extracorpórea , Hospitais de Veteranos , Choque Cardiogênico , United States Department of Veterans Affairs , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Estados Unidos , Choque Cardiogênico/terapia , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Insuficiência Respiratória/terapia , Procedimentos Cirúrgicos Cardíacos/métodos , Estudos Retrospectivos , Transferência de Pacientes
20.
Clin Transplant ; 38(1): e15242, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38289895

RESUMO

INTRODUCTION: Incidental kidneys cysts are typically considered benign, but the presence of cysts is more frequent in individuals with other early markers of kidney disease. We studied the association of donor kidney cysts with donor and recipient outcomes after living donor kidney transplantation. METHODS: We retrospective identified 860 living donor transplants at our center (1/1/2011-7/31/2022) without missing data. Donor cysts were identified by review of pre-donation CT scan reports. We used linear regression to study the association between donor cysts and 6-month single-kidney estimated glomerular filtration rate (eGFR) increase, and time-to-event analyses to study the association between donor cysts and recipient death-censored graft failure. RESULTS: Among donors, 77% donors had no kidney cysts, 13% had ≥1 cyst on the kidney not donated, and 11% only had cysts on the donated kidney. In adjusted linear regression, cysts on the donated kidney and kidney not donated were not significantly associated with 6-month single-kidney eGFR increase. Among transplants, 17% used a transplanted kidney with a cyst and 6% were from donors with cysts only on the kidney not transplanted. There was no association between donor cyst group and post-transplant death-censored graft survival. Results were similar in sensitivity analyses comparing transplants using kidneys with no cysts versus 1-2 cysts versus ≥3 cysts. CONCLUSIONS: Kidney cysts in living kidney donors were not associated with donor kidney recovery or recipient allograft longevity, suggesting incidental kidney cysts need not be taken into account when determining living donor candidate suitability or the laterality of planned donor nephrectomy.


Assuntos
Cistos , Transplante de Rim , Humanos , Doadores Vivos , Estudos Retrospectivos , Rim , Taxa de Filtração Glomerular , Sobrevivência de Enxerto
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