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1.
Cell Rep Med ; 5(9): 101738, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39293401

RESUMO

The gut microbiome is crucial for nutrient metabolism, immune regulation, and intestinal homeostasis with changes in its composition linked to complex diseases like inflammatory bowel disease (IBD). Although the precise host-microbial mechanisms in disease pathogenesis remain unclear, high-throughput sequencing have opened new ways to unravel the role of interspecies interactions in IBD. Systems biology-a holistic computational framework for modeling complex biological systems-is critical for leveraging multi-omics datasets to identify disease mechanisms. This review highlights the significance of multi-omics data in IBD research and provides an overview of state-of-the-art systems biology resources and computational tools for data integration. We explore gaps, challenges, and future directions in the research field aiming to uncover novel biomarkers and therapeutic targets, ultimately advancing personalized treatment strategies. While focusing on IBD, the proposed approaches are applicable for other complex diseases, like cancer, and neurodegenerative diseases, where the microbiome has also been implicated.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/genética , Biologia de Sistemas/métodos , Animais , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Proteômica/métodos , Metabolômica , Genômica/métodos , Multiômica
2.
J Surg Res ; 302: 883-890, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260043

RESUMO

INTRODUCTION: Robotic surgery continues to drive evolution in minimally invasive surgery. Due to the confined operative fields encountered, pediatric surgeons may uniquely benefit from the precise control offered by robotic technologies compared to open and laparoscopic techniques. We describe a unique collaborative implementation of robotic surgery into an academic pediatric surgery practice through adult robotic surgeon partnership. We compare robotic cholecystectomy (RC) and laparoscopic cholecystectomy (LC) outcomes, hypothesizing that RC will be equivalent to LC in key quality outcomes. METHODS: We evaluate 14 mo of systems development and training, and 24 mo of collaborative operative experience evoking a purposeful tiered case progression, establishing core robotic competencies, prior to advancing operative complexity. Univariate analyses compared LC versus RC. RESULTS: 36 robotic operations were performed in children aged 8-18 y, in a tiered progression from 24 cholecystectomies to 2 ileocecectomies, 2 paraesophageal hernia repairs, 1 anterior rectopexy, 1 spleen-preserving distal pancreatectomy, 1 Heller myotomy, 1 choledochal cyst resection with roux-en-y hepaticojejunostomy, 1 median arcuate ligament release, and 1 thoracic esophageal duplication cyst resection. For LC and RC, there were no significant differences in procedure duration, discharge opioids, hospital readmission, or rates of surgical site infection or bile duct injury. CONCLUSIONS: Robotic surgery has potential to significantly enhance pediatric surgery. RC appears equivalent to LC but presents multiple additional theoretical benefits in pediatric patients. Our pilot program experience supports the feasibility and safety of pediatric robotic surgery. We emphasize the importance of a stepwise progression in operative difficulty and collaboration with adult robotic surgery experts.

3.
Epilepsia ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39096434

RESUMO

OBJECTIVE: Stereoelectroencephalography (SEEG) is increasingly utilized worldwide in epilepsy surgery planning. International guidelines for SEEG terminology and interpretation are yet to be proposed. There are worldwide differences in SEEG definitions, application of features in epilepsy surgery planning, and interpretation of surgical outcomes. This hinders the clinical interpretation of SEEG findings and collaborative research. We aimed to assess the global perspectives on SEEG terminology, differences in the application of presurgical features, and variability in the interpretation of surgery outcome scores, and analyze how clinical expert demographics influenced these opinions. METHODS: We assessed the practices and opinions of epileptologists with specialized training in SEEG using a survey. Data were qualitatively analyzed, and subgroups were examined based on geographical regions and years of experience. Primary outcomes included opinions on SEEG terminology, features used for epilepsy surgery, and interpretation of outcome scores. Additionally, we conducted a multilevel regression and poststratification analysis to characterize the nonresponders. RESULTS: A total of 321 expert responses from 39 countries were analyzed. We observed substantial differences in terminology, practices, and use of presurgical features across geographical regions and SEEG expertise levels. The majority of experts (220, 68.5%) favored the Lüders epileptogenic zone definition. Experts were divided regarding the seizure onset zone definition, with 179 (55.8%) favoring onset alone and 135 (42.1%) supporting onset and early propagation. In terms of presurgical SEEG features, a clear preference was found for ictal features over interictal features. Seizure onset patterns were identified as the most important features by 265 experts (82.5%). We found similar trends after correcting for nonresponders using regression analysis. SIGNIFICANCE: This study underscores the need for standardized terminology, interpretation, and outcome assessment in SEEG-informed epilepsy surgery. By highlighting the diverse perspectives and practices in SEEG, this research lays a solid foundation for developing globally accepted terminology and guidelines, advancing the field toward improved communication and standardization in epilepsy surgery.

4.
J Neural Eng ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39178901

RESUMO

OBJECTIVE: The proportion of patients becoming seizure-free after epilepsy surgery has stagnated. Large multi-center stereo-electroencephalography datasets can allow comparing new patients to past similar cases and making clinical decisions with the knowledge of how cases were treated in the past. However, the complexity of these evaluations makes the manual search for similar patients impractical. We aim to develop an automated system that electrographically and anatomically matches seizures to those in a database. Additionally, since features that define seizure similarity are unknown, we evaluate the agreement and features among experts in classifying similarity. Approach: We utilized 320 stereo-electroencephalography seizures from 95 consecutive patients who underwent epilepsy surgery. Eight international experts evaluated seizure-pair similarity using a four-level similarity score. As our primary outcome, we developed and validated an automated seizure matching system by employing patient data marked by independent experts. Secondary outcomes included the inter-rater agreement and features for classifying seizure similarity. Main results: The seizure matching system achieved a median area-under-the-curve of 0.76 (interquartile range, 0.1), indicating its feasibility. Six distinct seizure similarity features were identified and proved effective: onset region, onset pattern, propagation region, duration, extent of spread, and propagation speed. Among these features, the onset region showed the strongest correlation with expert scores (Spearman's rho=0.75, p<0.001). Additionally, the moderate inter-rater agreement confirmed the practicality of our approach with an agreement of 73.9% (7%), and Gwet's kappa of 0.45 (0.16). Further, the interoperability of the system was validated on seizures from five centers. Significance: We demonstrated the feasibility and validity of a stereo-electroencephalography seizure matching system across patients, effectively mirroring the expertise of epileptologists. This novel system can identify patients with seizures similar to that of a patient being evaluated, thus optimizing the treatment plan by considering the results of treating similar patients in the past, potentially improving surgery outcome. .

5.
Epilepsia ; 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180417

RESUMO

OBJECTIVE: In addition to the oscillatory brain activity, the nonoscillatory (scale-free) components of the background electroencephalogram (EEG) may provide further information about the complexity of the underlying neuronal network. As epilepsy is considered a network disease, such scale-free metrics might help to delineate the epileptic network. Here, we performed an analysis of the sleep oscillatory (spindle, slow wave, and rhythmic spectral power) and nonoscillatory (H exponent) intracranial EEG using multiple interictal features to estimate whether and how they deviate from normalcy in 38 adults with drug-resistant epilepsy. METHODS: To quantify intracranial EEG abnormalities within and outside the seizure onset areas, patients' values were adjusted based on normative maps derived from the open-access Montreal Neurological Institute open iEEG Atlas. In a subset of 29 patients who underwent resective surgery, we estimated the predictive value of these features to identify the epileptogenic zone in those with a good postsurgical outcome. RESULTS: We found that distinct sleep oscillatory and nonoscillatory metrics behave differently across the epileptic network, with the strongest differences observed for (1) a reduction in spindle activity (spindle rates and rhythmic sigma power in the 10-16 Hz band), (2) a higher rhythmic gamma power (30-80 Hz), and (3) a higher H exponent (steeper 1/f slope). As expected, epileptic spikes were also highest in the seizure onset areas. Furthermore, in surgical patients, the H exponent achieved the highest performance (balanced accuracy of .76) for classifying resected versus nonresected channels in good outcome patients. SIGNIFICANCE: This work suggests that nonoscillatory components of the intracranial EEG signal could serve as promising interictal sleep candidates of epileptogenicity in patients with drug-resistant epilepsy. Our findings further advance the understanding of epilepsy as a disease, whereby absence or loss of sleep physiology may provide information complementary to pathological epileptic processes.

6.
J R Coll Physicians Edinb ; : 14782715241265144, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39069719

RESUMO

A 57-year-old man with a background of chronic pancreatitis presented with acutely worsening abdominal pain and vomiting. He previously had a pancreatic duct stent in situ which had been removed 1 year prior to presentation. Initially suspected to be acute-on-chronic pancreatitis, a computed tomography (CT) scan of the abdomen and pelvis revealed an atrophic pancreas and a new mass in the pancreatic head, raising the suspicion of pancreatic malignancy. An urgent endoscopic ultrasound (EUS)-guided fine needle biopsy of the pancreatic head mass surprisingly revealed the presence of actinomyces colonies on histological evaluation. Prompt initiation of a prolonged antibiotic course led to significant clinical and radiological improvement. This case highlights the rare presentation of pancreatic actinomycosis which can often masquerade as malignancy. Although a gut commensal, actinomyces can elicit pathogenic effects if allowed to enter tissues through a breach in the mucosal lining such as following abdominal surgery or pancreatic duct intervention as observed in this case. Early recognition and appropriate treatment with antibiotics can lead to clinical recovery and complete resolution of the infection.

7.
J Hand Surg Glob Online ; 6(2): 227-232, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38903832

RESUMO

Purpose: Distal radius fractures (DRFs) indicated for operative intervention are most commonly treated with volar-locked plating (VLP); however, dorsal bridge plating (DBP) has been used as an alternative fixation method. The purpose of this study was to use a propensity score to match and compare the radiographic and clinical outcomes of patients undergoing isolated VLP or DBP for DRFs. Methods: We performed a retrospective, propensity score-matched analysis of patients undergoing isolated VLP or DBP treatment for isolated DRFs from 2015 to 2022 at a single level-1 trauma center. Patients were propensity score-matched by a total of eight demographic and comorbidity factors, AO Foundation/Orthopedic Trauma Association classification, and preoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores. Our primary outcomes included postoperative complications, wrist and forearm range of motion (ROM), grip strength, and radiographic measurements, including radial height, radial inclination, volar tilt, and articular step-off. Results: Overall, 415 DBP and 2075 VLP were successfully propensity score-matched and included in this study. Grip strength and ROM measurements at the 6-month follow-up, including wrist flexion, wrist extension, forearm pronation, forearm supination, radial deviation, and ulnar deviation, were increased in the VLP compared with DBP (P < .05). Complication rates among both the groups were relatively low; however, the rates of malunion and nonunion were significantly higher among the DBP group (P < .05). Radial height, radial inclination, and articular step-off were improved in the VLP group compared with the DBP group (P < .05); however, volar tilt was similar between groups. PROMIS upper extremity and physical function were significantly higher among the VLP group (P < .05). No significant difference was noted in PROMIS pain interference between the groups. Conclusions: When compared with DBP, patients undergoing VLP are more likely to have improved clinical and radiographic outcomes. Although improvement in wrist and forearm ROM and radiographic parameters is statistically significant, it may not be clinically relevant. Type of study/level of evidence: Therapeutic III.

8.
Eur Radiol ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842692

RESUMO

OBJECTIVES: To develop an automated pipeline for extracting prostate cancer-related information from clinical notes. MATERIALS AND METHODS: This retrospective study included 23,225 patients who underwent prostate MRI between 2017 and 2022. Cancer risk factors (family history of cancer and digital rectal exam findings), pre-MRI prostate pathology, and treatment history of prostate cancer were extracted from free-text clinical notes in English as binary or multi-class classification tasks. Any sentence containing pre-defined keywords was extracted from clinical notes within one year before the MRI. After manually creating sentence-level datasets with ground truth, Bidirectional Encoder Representations from Transformers (BERT)-based sentence-level models were fine-tuned using the extracted sentence as input and the category as output. The patient-level output was determined by compilation of multiple sentence-level outputs using tree-based models. Sentence-level classification performance was evaluated using the area under the receiver operating characteristic curve (AUC) on 15% of the sentence-level dataset (sentence-level test set). The patient-level classification performance was evaluated on the patient-level test set created by radiologists by reviewing the clinical notes of 603 patients. Accuracy and sensitivity were compared between the pipeline and radiologists. RESULTS: Sentence-level AUCs were ≥ 0.94. The pipeline showed higher patient-level sensitivity for extracting cancer risk factors (e.g., family history of prostate cancer, 96.5% vs. 77.9%, p < 0.001), but lower accuracy in classifying pre-MRI prostate pathology (92.5% vs. 95.9%, p = 0.002) and treatment history of prostate cancer (95.5% vs. 97.7%, p = 0.03) than radiologists, respectively. CONCLUSION: The proposed pipeline showed promising performance, especially for extracting cancer risk factors from patient's clinical notes. CLINICAL RELEVANCE STATEMENT: The natural language processing pipeline showed a higher sensitivity for extracting prostate cancer risk factors than radiologists and may help efficiently gather relevant text information when interpreting prostate MRI. KEY POINTS: When interpreting prostate MRI, it is necessary to extract prostate cancer-related information from clinical notes. This pipeline extracted the presence of prostate cancer risk factors with higher sensitivity than radiologists. Natural language processing may help radiologists efficiently gather relevant prostate cancer-related text information.

9.
Biotechnol Bioeng ; 121(9): 2662-2677, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38708676

RESUMO

Gene therapy using recombinant adeno-associated virus (rAAV) as delivery vehicles has garnered much interest in recent years. There are still significant gaps in our fundamental understanding of the manufacturing processes to deliver sufficient products. Manufacturing efforts of rAAV using HEK293 cells have commonly relied on fixed bed falling film bioreactors like the iCELLis®. We used computational fluid dynamics (CFD) to validate the operating conditions required for a predictive iCELLis® 500 scale-down model. The small-scale and at-scale systems have different flow paths causing validation of the corresponding agitation rates required to achieve the same linear flow through the fixed bed across scales to be non-trivial. Therefore, we used CFD to predict the theoretical scaling relationship. In addition, CFD could predict kLa differences between the two systems and the operating conditions required to match kLa between scales. We also confirmed that the location of DO control must be the same in both systems to achieve proper scaling. Experimental runs confirming the validity of the novel scale-down model showed that based on the modifications to the iCELLis® Nano system, we achieved similar DO, key metabolite, pH, and GC titer trends in both systems.


Assuntos
Reatores Biológicos , Dependovirus , Terapia Genética , Hidrodinâmica , Dependovirus/genética , Humanos , Terapia Genética/métodos , Células HEK293 , Simulação por Computador , Vetores Genéticos/genética
10.
J Biotechnol ; 388: 96-106, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38642816

RESUMO

Bioprocess scale-up and technology transfer can be challenging due to multiple variables that need to be optimized during process development from laboratory scale to commercial manufacturing. Cell cultures are highly sensitive to key factors during process transfer across scales, including geometric variability in bioreactors, shear stress from impeller and sparging activity, and nutrient gradients that occur due to increasing blend times. To improve the scale-up and scale-down of these processes, it is important to fully characterize bioreactors to better understand the differences that will occur within the culture environment, especially the hydrodynamic profiles that will vary in vessel designs across scales. In this study, a comprehensive hydrodynamic characterization of the Ambr® 250 mammalian single-use bioreactor was performed using time-accurate computational fluid dynamics simulations conducted with M-Star computational fluid dynamics software, which employs lattice-Boltzmann techniques to solve the Navier-Stokes transport equations at a mesoscopic scale. The single-phase and two-phase fluid properties within this small-scale vessel were analyzed in the context of agitation hydrodynamics and mass transfer (both within the bulk fluid and the free surface) to effectively characterize and understand the differences that scale-down models possess when compared to their large-scale counterparts. The model results validate the use of computational fluid dynamics as an in-silico tool to characterize bioreactor hydrodynamics and additionally identify important free-surface transfer mechanics that need to be considered during the qualification of a scale-down model in the development of mammalian bioprocesses.


Assuntos
Reatores Biológicos , Técnicas de Cultura de Células , Simulação por Computador , Hidrodinâmica , Animais , Técnicas de Cultura de Células/métodos , Gases/metabolismo , Cricetulus , Células CHO , Modelos Biológicos
11.
Cureus ; 16(2): e53623, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38449952

RESUMO

Acute vision loss is a prevalent clinical manifestation associated with a broad spectrum of differential diagnoses, encompassing demyelinating diseases, neoplastic processes, autoimmune disorders, and infectious conditions. A rare but noteworthy infectious etiology contributing to acute vision loss is neurological Lyme disease (Lyme neuroborreliosis)-induced optic neuritis. Lyme disease, a vector-borne illness caused by the spirochete Borrelia burgdorferi, has the potential to affect multiple physiological systems and unfolds in three distinct stages. Another significant contributor to acute vision loss is giant cell arteritis, an autoimmune vasculitis that commonly affects large- and medium-sized vessels, including the temporal and ophthalmic arteries. This relatively common condition may manifest with symptoms, such as jaw claudication, headaches, and visual disturbances. The precise identification of the underlying cause of acute visual loss is of utmost importance for physicians, as it is instrumental in averting undesirable complications. An 80-year-old female presents to the emergency room with a sudden onset of blurry vision of the left eye, right-sided weakness, dysarthria, jaw pain, headache, and left facial droop. Following consultations with rheumatology and ophthalmology specialists, giant cell arteritis emerged as a primary consideration in the differential diagnosis for the observed vision loss. Subsequently, a temporal artery biopsy was conducted, definitively confirming the diagnosis of giant cell arteritis. Considering the patient's residence in an area endemic to Lyme disease, a Lyme immunoglobulin G (IgG) titer was ordered. The results returned positive, suggesting the presence of Lyme neuroborreliosis.

12.
J Hand Surg Glob Online ; 6(1): 58-61, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38313628

RESUMO

Purpose: Perilunate fracture dislocation (PLFD) injuries are associated with the development of acute carpal tunnel syndrome (CTS). The purpose of our study was to identify the factors that increase the likelihood of developing CTS in patients with PLFD. Additionally, we attempted to classify patients who did not initially undergo carpal tunnel release (CTR) at the time of injury but eventually underwent CTR within the follow-up period. Methods: Patients presenting to a level-1 trauma center with isolated PLFDs (Mayfield III-IV) were retrospectively identified by using CPT and ICD-10 codes. Polytraumatized patients, those with a history of previous wrist trauma, or those with previous carpal tunnel symptoms or surgery were excluded. Outcomes of interest included the development of acute CTS, pre- and post-reduction changes in CTS symptoms, and associated hand and wrist fractures. Chi-square tests, Kruskal-Wallis tests, and multivariate logistic regression were used to examine the predictors of developing CTS after a PLFD. Results: In total, 43 patients were included in the final cohort, with a mean age of 44 years, of which 77% were men. The most common fracture of the carpus included scaphoid fractures (9/43, 21%). The average time from presentation to reduction was 636 minutes. Acute CTS symptoms before reduction were present in 26% of the patients and increased post-reduction to 28%. No difference exists between the time to sedation and the presence of acute carpal tunnel symptoms (P >.05). During initial surgical intervention, 79% underwent CTR (27/34). Of the seven patients who did not initially undergo a CTR, 57% (4/7) required a CTR within the follow-up period. Conclusion: Reduction of PLFDs did not significantly improve the number of patients with acute CTS. More than 50% of the patients who did not undergo a CTR at the initial surgery required a CTR within the follow-up period. Type of study/level of evidence: Prognostic III.

13.
Brain ; 147(7): 2496-2506, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38325327

RESUMO

We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone compared with other leading interictal biomarkers in a multicentre, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centres who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection [International League Against Epilepsy Class 1 outcome (ILAE 1)] and those with persistent seizures (ILAE 2-6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80-500 Hz), ripple (80-250 Hz) and fast ripple (250-500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Overall, 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001 and P < 0.001, respectively). Among ILAE 1 subjects, the mean spike ripple rate was higher in the resected volume (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared with ILAE 2-6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01) or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicentre cohort, when surgical resection was successful, the majority of spike ripples were removed. Furthermore, automatically detected spike ripples localize the epileptogenic tissue better than spikes, spike-gamma, wideband HFOs, ripples and fast ripples.


Assuntos
Eletrocorticografia , Humanos , Masculino , Feminino , Adulto , Eletrocorticografia/métodos , Adulto Jovem , Adolescente , Eletroencefalografia/métodos , Pessoa de Meia-Idade , Epilepsia/fisiopatologia , Epilepsia/cirurgia , Criança , Ondas Encefálicas/fisiologia , Encéfalo/fisiopatologia
14.
J Indian Assoc Pediatr Surg ; 29(1): 19-22, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405251

RESUMO

Aims: Intussusception is a common pediatric surgical emergency and an indicator for primary healthcare. We report our experience with childhood intussusception at a tertiary care hospital in the private sector in Central Kerala and add our refinement to the technique of hydrostatic saline reduction which had more desirable outcome. Settings and Design: Children presenting with the diagnosis of intussusception which were managed in our department of pediatric surgery at a private hospital in Kerala, India. Subjects and Methods: Eighty children, up to 15 years of age, (43 boys, 37 girls) confirmed to have intussusception on ultrasound and managed in our institution from October 2016 to July 2020 with hydrostatic saline reduction. Sixty-two (77%) of them were aged 3 months to 3 years (numbers <10 to be written in words); the age of idiopathic intussusception. Statistical Analysis Used: SPSS V25. Association between variables using Chi square test and independent t test. Results: A total of 80 children met the criteria out of that (n = 79) had successful nonoperative reduction. Hydrostatic saline enema 73, One Barium and five air enema. A child presented in shock was taken up for laparotomy and reduced operatively. Six recurred within 24 h (7% early recurrence) and a second attempt at nonoperative reduction succeeded in all six of them. (numbers <10 in words). Eleven children (14%) had a late recurrence, the attempt at saline hydrostatic reduction was successful in only 3 (27%) and 8 went on to have surgery. Six were successfully reduced operatively and 2 had resection anastomosis. Conclusions: After excluding those who need surgery on clinical grounds, we report a 98.7% success with nonoperative reduction for the first instance of intussusception, a 24 h recurrence of 7%, with successful repeat reductions in all. With the refinement in the technique, we could achieve a desirable outcome. At the first presentation, surgery was indicated in 1 of the 80 children. We report a late recurrence rate of 14%, with a 27% success rate for nonoperative reduction. No pathological lead points were identified even in this group. All the children had an uneventful and a faster recovery. In our series, we had 97.5% follow-up rate.

15.
Sci Adv ; 9(49): eadl2108, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38055822

RESUMO

The catalytic cycle of topoisomerase 2 (TOP2) enzymes proceeds via a transient DNA double-strand break (DSB) intermediate termed the TOP2 cleavage complex (TOP2cc), in which the TOP2 protein is covalently bound to DNA. Anticancer agents such as etoposide operate by stabilizing TOP2ccs, ultimately generating genotoxic TOP2-DNA protein cross-links that require processing and repair. Here, we identify RAD54 like 2 (RAD54L2) as a factor promoting TOP2cc resolution. We demonstrate that RAD54L2 acts through a novel mechanism together with zinc finger protein associated with tyrosyl-DNA phosphodiesterase 2 (TDP2) and TOP2 (ZATT/ZNF451) and independent of TDP2. Our work suggests a model wherein RAD54L2 recognizes sumoylated TOP2 and, using its ATPase activity, promotes TOP2cc resolution and prevents DSB exposure. These findings suggest RAD54L2-mediated TOP2cc resolution as a potential mechanism for cancer therapy resistance and highlight RAD54L2 as an attractive candidate for drug discovery.


Assuntos
Adutos de DNA , Proteínas de Ligação a DNA , Humanos , Adutos de DNA/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Diester Fosfórico Hidrolases/genética , DNA Topoisomerases Tipo II/genética , DNA/genética , Instabilidade Genômica , DNA Helicases/genética
16.
J Hand Surg Glob Online ; 5(6): 849-851, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38106933

RESUMO

We present the case of a 54-year-old right-handed woman with no medical history of rheumatic disease or trauma to the upper extremities who developed painful nodules along her left upper extremity and torso immediately after receiving the mRNA-1273 SARS-CoV-2 vaccine booster for COVID-19 in her left upper extremity. Most of the nodules subsided within several days, but several persisted over the dorsum of the left wrist with physical examination and imaging findings consistent with second and fourth extensor compartment tenosynovitis. She ultimately underwent excision of the left wrist extensor tenosynovitis, followed by a repeat excision for recurrence of symptoms.

17.
J Orthop ; 46: 102-106, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37969227

RESUMO

Study design: Retrospective Multi-Institutional Database Study. Objective: Investigate the effect of metabolic syndrome (MetS) on the outcomes of Transforaminal Lumbar Interbody Fusion (TLIF). Summary of background data: TLIF procedures in lumbar spine pathology are common. MetS is a combination of conditions, including medication required hypertension, diabetes mellitus (DM), and body mass index (BMI) of 30 kg/m2s or more. The prevalence of MetS has increased drastically over the past two decades. Our study aimed to understand the effect of MetS on morbidity and mortality of TLIF postoperatively. Methods: Our study used American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) data from 2006 to 2019 to find all patients who underwent TLIF. Patients with MetS were compared to those without MetS. Fisher's test identified univariate relationships between MetS and preoperative/postoperative variables. Multivariable logistic regression models were utilized to analyze the association between MetS and postoperative morbidity and mortality. Results: 54,980 patients were identified who received TLIF. 10.7 % had MetS preoperatively. Patients with and without MetS showed statistically significant univariate differences in most preoperative and postoperative variables. After adjusting for preoperative comorbidities, patients with MetS had greater multivariate-adjusted odds of wound infections (aOR = 1.5889, CI 1.1952-2.112, p = 0.00144), pulmonary events (aOR = 1.5517, CI 1.1207-2.1485, p = 0.00813), renal events (aOR = 2.8685, CI 1.5511-5.3045, p = 0.00078), sepsis (aOR = 1.6773, CI 1.1647-2.4155, p = 5.44E-03), and return to OR (aOR = 1.4764, CI 1.2201-1.7866, p = 6.19E-05). Conclusions: Patients with MetS are at elevated risk for various morbidity and mortality markers after TLIF. Surgeons performing TLIFs on these patients should be aware of the increased potential for postoperative events that may complicate the patient's recovery. Level of evidence: Level III.

18.
Cureus ; 15(10): e46515, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37927648

RESUMO

Physicians regularly use corticosteroids to treat various conditions, attributing their anti-inflammatory and immunosuppressive properties. Cases of allergic sensitivity reactions and dermatitis induced by corticosteroids are relatively uncommon. We present a case regarding an 81-year-old male with a history of actinic keratosis, atopic dermatitis, and psoriasis, who experienced a Type I hypersensitivity reaction with facial angioedema and urticaria on his axilla, torso, and popliteal fossa that developed after treatment with oral prednisolone. This episode also exacerbated his previously diagnosed psoriasis. To treat psoriasis, a dermatologist prescribed clobetasol topical ointment, which did not alleviate the symptoms; instead, it only exacerbated the rash, and he was subsequently referred for corticosteroid allergy testing. North American 85 Comprehensive Series patch testing revealed a positive test for various classes of steroids, including clobetasol-17-propionate, budesonide, and dexamethasone, thus proving a T cell-mediated allergy to corticosteroids.

19.
Eur Radiol ; 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37889268

RESUMO

OBJECTIVES: To evaluate the impact of susceptibility artifacts from hip prosthesis on cancer detection rate (CDR) in prostate MRI. MATERIALS AND METHODS: This three-center retrospective study included prostate MRI studies for patients without known prostate cancer between 2017 and 2021. Exams with hip prosthesis were searched on MRI reports. The degree of susceptibility artifact on diffusion-weighted images was retrospectively categorized into mild, moderate, and severe (> 66%, 33-66%, and < 33% of the prostate volume are evaluable) by blind reviewers. CDR was defined as the number of exams with Gleason score ≥7 detected by MRI (PI-RADS ≥3) divided by the total number of exams. For each artifact grade, control exams without hip prosthesis were matched (1:6 match), and CDR was compared. The degree of CDR reduction was evaluated with ratio, and influential factors were evaluated by expanding the equation. RESULTS: Hip arthroplasty was present in 548 (4.8%) of the 11,319 MRI exams. CDR of the cases and matched control exams for each artifact grade were as follows: mild (n = 238), 0.27 vs 0.25, CDR ratio = 1.09 [95% CI: 0.87-1.37]; moderate (n = 143), 0.18 vs 0.27, CDR ratio = 0.67 [95% CI: 0.46-0.96]; severe (n = 167), 0.22 vs 0.28, CDR ratio = 0.80 [95% CI: 0.59-1.08]. When moderate and severe artifact grades were combined, CDR ratio was 0.74 [95% CI: 0.58-0.93]. CDR reduction was mostly attributed to the increased frequency of PI-RADS 1-2. CONCLUSION: With moderate to severe susceptibility artifacts from hip prosthesis, CDR was decreased to 74% compared to the matched control. CLINICAL RELEVANCE STATEMENT: Moderate to severe susceptibility artifacts from hip prosthesis may cause a non-negligible CDR reduction in prostate MRI. Expanding indications for systematic prostate biopsy may be considered when PI-RADS 1-2 was assigned. KEY POINTS: • We proposed cancer detection rate as a diagnostic performance metric in prostate MRI. • With moderate to severe susceptibility artifacts secondary to hip arthroplasty, cancer detection rate decreased to 74% compared to the matched control. • Expanding indications for systematic prostate biopsy may be considered when PI-RADS 1-2 is assigned.

20.
J Hand Surg Am ; 48(12): 1229-1235, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37877916

RESUMO

PURPOSE: Given the relatively high false negative rate of electrodiagnostic studies (EDX) in patients with clinically diagnosed ulnar neuropathy at the elbow (UNE), we sought to determine whether an alternative objective test could more effectively detect UNE. Additionally, we proposed to determine the relationship between the cross-sectional area (CSA) of the ulnar nerve on ultrasound (US), EDX, and clinical symptoms. METHODS: This was a retrospective study of patients presenting with symptomatic UNE. The performance characteristics of EDX versus ultrasound were calculated using the clinical diagnosis of UNE as the reference standard. Standard EDX studies and US of the ulnar nerve were analyzed. Maximal CSA of the ulnar nerve and EDX severity were analyzed for patients with each combination of US-positive/negative and EDX-positive/negative findings. RESULTS: Analysis was performed on 89 patients and 115 nerves with signs and symptoms of cubital tunnel syndrome. In total, 56 (49%) nerves were diagnosed as mild UNE, 32 (28%) nerves were diagnosed as moderate UNE, 17 (15%) nerves were diagnosed as severe UNE, and 10 (8%) nerves were negative for UNE by EDX. Maximal-maximal CSA was highly correlated with disease severity as determined by nerve conduction studies/electromyography. Compared with EDX+/US+, patients with EDX-/US+ showed higher rates of ulnar sensory loss and elbow tenderness with similar rates of positive Tinel and intrinsic muscle atrophy. In this sample of patients with clinically diagnosed UNE, 91.3% of the patients demonstrated positive EDX studies, whereas 94.8% had a positive US. CONCLUSIONS: Ultrasound is an alternative to EDX that could be incorporated clinically in the diagnosis and management of UNE. Ultrasound was able to consistently detect clinically positive cubital tunnel syndrome demonstrating its utility as a confirmatory or supplemental test to the clinical assessment if one is required. Ultrasound additionally may be able to better identify patients with early stages of UNE with negative EDX findings. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.


Assuntos
Síndrome do Túnel Ulnar , Articulação do Cotovelo , Neuropatias Ulnares , Humanos , Cotovelo/diagnóstico por imagem , Síndrome do Túnel Ulnar/diagnóstico por imagem , Estudos Retrospectivos , Neuropatias Ulnares/diagnóstico por imagem , Nervo Ulnar/diagnóstico por imagem , Condução Nervosa/fisiologia , Eletrodiagnóstico
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