Citations

AbstractAcute pancreatitis (AP) is a severe inflammatory condition of the pancreas with significant morbidity and mortality, particularly in its necrotizing form. This review explores the management of peripancreatic collections and in particular necrotizing pancreatitis, focusing on the evolution from traditional open surgical methods to contemporary minimally invasive image-guided techniques. AP can lead to various local complications, including pancreatic pseudocysts, acute necrotic collections, and walled-off necrosis. Imaging plays a crucial role in diagnosing complications of AP, while treatment approaches have shifted toward a step-up strategy involving percutaneous, endoscopic, and minimally invasive methods. Percutaneous necrosectomy, combining mechanical and chemical debridement, has shown promising results. Mechanical necrosectomy uses devices like baskets and retrieval nets, while chemical necrosectomy adds agents like hydrogen peroxide and streptokinase. Current evidence suggests that the step-up approach, starting with percutaneous drainage or necrosectomy and escalating to endoscopic or surgical interventions, if necessary, improves patient outcomes. The review underscores the need for a multidisciplinary approach in managing complicated AP and highlights ongoing advancements in minimally invasive techniques.

AbstractHistorically, cementless patellar implants were fraught with issues of fixation and polyethylene wear. However, contemporary cementless patellar implants incorporate modern technologies for implant design and offer the potential for improved biological fixation and longevity. As such, an evaluation of the performance of modern cementless patellae is needed. The purpose of this study was to perform a systematic review and meta-analysis of contemporary cementless patellar implants used during primary total knee arthroplasty (TKA), with a particular focus on aseptic loosening of the patellar component. A systematic review of the literature was performed from January 2000 to February 22, 2024. We included all peer-reviewed studies that reported the number of revisions in patients who had cementless patellae placed in 2000 or later during primary TKA. Reviews and case reports were excluded. Out of 639 studies, 13 were included with a total of 3,005 cementless patellae analyzed. The mean patient age was 64 years and the mean body mass index (BMI) was 31 kg/m2. Meta-analyses were performed to calculate the pooled revision rate per person-year of revision for aseptic loosening of the patellar component and revision for any patellar failure. Upon analysis of 13 studies involving a total of 3,005 cementless patellae, the revision rate for aseptic loosening of the patella was 0.2 per 1,000 person-years and the revision rate for any patellar failure was 1 per 1,000 person-years. Contemporary cementless patellar implants showed an overall revision rate of 1 per 1,000 person-years, demonstrating excellent longevity. The high survivorship, together with a low rate of loosening, show the utility and effectiveness of these implants. Given the nature of biologic fixation, these results are promising for long-term implant stability but additional follow-up is warranted.

Abstract Cholecystectomy (CCY) is the standard treatment for acute cholecystitis. For non-surgical patients, percutaneous cholecystostomy tube (PT-GBD) is recommended but is associated with high readmission rates and poor quality of life. Endoscopic gallbladder decompression techniques, including endoscopic transpapillary gallbladder drainage (ET-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD), are alternatives. Studies comparing ET-GBD and EUS-GBD have shown EUS-GBD to have superior outcomes. However, these studies assessed ET-GBD mostly via single transcystic stent placement (SSET-GBD). This study aimed to compare outcomes of dual transcystic stents (DSET-GBD) and EUS-GBD in non-surgical candidates with acute cholecystitis. A multicenter analysis was conducted on patients who underwent ET-GBD or EUS-GBD between January 2019 and January 2023. Data were extracted from electronic medical records and outcomes including technical success, success, adverse events (AEs), and recurrence rates of cholecystitis were measured. Of 129 procedures (56 EUS-GBD; 73 ET-GBD), technical success was achieved in 87.5% of EUS-GBD and 86.3% of ET-GBD attempts. Immediate clinical success was achieved in 98.1% for EUS-GBD and 100% for DSET-GBD. AE rates were similar between the groups. Recurrent cholecystitis rates were 5.3% for EUS-GBD and 8.2% for DSET-GBD (P = 0.692). This study demonstrates that DSET-GBD has similarly low rates of recurrent acute cholecystitis compared with EUS-GBD. DSET-GBD should be considered as an alternative management strategy for management of acute cholecystitis in patients who are unable to undergo CCY.

Abstract Immune reactions to medical implants often lead to encapsulation by fibrotic tissue and impaired device function. This process is thought to initiate by protein adsorption, which enables immune cells to attach and mount an inflammatory response. Previously, several antifibrotic materials have been either designed to reduce protein adsorption or discovered via high‐throughput screens (HTS) to favorably regulate inflammation. The present work introduces antifouling immunomodulatory (AIM) copolymer coatings, which combine both strategies to effectively enhance implant protection. AIM copolymers synergistically integrate zwitterionic moieties to resist protein fouling, HTS‐derived antifibrotics for immunomodulation, and silane monomers for grafting to diverse substrates including elastomers, ceramics, and metals. Interestingly, simply combining these monomers into conventional random or block copolymer architectures yielded no significant advantage over homopolymers. By contrast, an unusual polymer chain architecture — a zwitterionic block flanked by a mixed zwitterionic immunomodulatory segment — showed superior fibrosis resistance in both peritoneal and subcutaneous sites over one month in immunocompetent mice. This architecture also improved the performance of two different HTS‐derived antifibrotic monomers, suggesting that tailoring AIM architectures may broadly complement immunomodulatory chemistries and provide a versatile approach to improving implant longevity.

ResumenLa tabaquera anatómica, una región triangular en la porción dorso-radial de la muñeca, es un punto de referencia anatómico clave. Está delimitada por los tendones del extensor largo del pulgar, extensor corto del pulgar y abductor largo del pulgar, y alberga la arteria radial y ramas nerviosas. Patologías como quistes sinoviales, fracturas y osteofitos pueden alterar su apariencia. Estudios sobre lesiones del ligamento escafolunar (SLL) muestran que el daño crónico provoca el desplazamiento dorso-radial del escafoides, iniciando un proceso degenerativo conocido como colapso avanzado escafolunar (SLAC). Esto a menudo resulta en la "desaparición" de la tabaquera anatómica, lo que facilita la identificación de pacientes con muñeca SLAC junto con síntomas como dolor y rigidez. La afección es impulsada por la formación de osteofitos, subluxación del escafoides y sinovitis, lo que conduce a inestabilidad articular y deformidad. Los tratamientos tradicionales, como la estiloidectomía, pueden no resolver completamente la inestabilidad. Nuevos enfoques que consideran la dinámica tridimensional de la muñeca podrían ser más efectivos para manejar el SLAC. Estudios biomecánicos sugieren que las lesiones del SLL, junto con la pérdida de estabilizadores secundarios, provocan que el escafoides se pronuncie y flexione, resultando en una proyección dorso-radial dentro de la fosa del escafoides. Sin tratamiento, esto puede progresar a SLAC, frecuentemente caracterizado por el "bulto dorso-radial de la muñeca".

ABSTRACTBackgroundThe self‐expanding, supra‐annular Evolut valve is an established platform for Transcatheter Aortic Valve Implantation (TAVI). Evolut PRO introduced an outer sealing wrap to mitigate paravalvular leakage. We evaluated the 3‐year clinical outcomes and valve performance of the Evolut PRO in standard clinical practice for severe aortic stenosis (AS) patients at intermediate or higher risk for surgery.MethodsThe FORWARD PRO prospective, single‐arm, multicentre, post‐market clinical study enrolled 638 patients with native aortic valve stenosis or failed surgical bioprosthetic aortic valve undergoing TAVI, at intermediate or high risk, with the Evolut PRO valve. Clinical and serial echocardiographic outcomes were followed‐up for 3 years.ResultsTAVI using Evolut PRO was attempted in 629 AS patients (implanted in 97%) (mean age 81.7 years; STS PROM score, 4.7%). At 3 years all‐cause mortality was 25.0%, disabling stroke 6.5% (all‐cause mortality or disabling stroke, 28.5%) and rate of new permanent pacemaker implantation 24.7%. Excellent valve haemodynamics were maintained (mean gradient 8.8 ± 4.7 mm Hg; mean effective orifice area 2.0 ± 0.5 cm2) at 3 years. In a paired analysis of patients with ≥ mild paravalvular leakage (PVL) at discharge, more than two‐thirds demonstrated improved PVL at 3 years. Patients with ≥ mild PVL at discharge had higher median total calcium volume than those with no/trace PVL (p < 0.001).ConclusionsIn clinical practice TAVI with the Evolut PRO valve is associated with favorable clinical outcomes and excellent haemodynamic performance out to 3 years. The observation of improvements in PVL over time warrants further research.

Introduction Plasmablastic lymphoma (PBL) is a rare aggressive subtype of lymphoma. It is more common in HIV positive patients, and is often associated with Epstein-Barr virus (EBV) and MYC rearrangements. PBL is characterized by markers of plasmacytic differentiation including CD138 and MUM1/IRF4, and loss of B-cell markers such as CD20, which suggests a cell of origin similar to that of multiple myeloma (MM) or activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL). The standard of care for PBL is CHOP-based chemotherapy but this is frequently not curative. Other than EBV-negative status, which defines a high-risk group, no other biological features have been discovered that are associated with outcomes. Methods Here, we provide a comprehensive analysis of the genomic and transcriptomic landscape of PBL using a collection of 176 exomes and genomes (n=55 new, contributed by Lymphoma/Leukemia Molecular Profiling Project [LLMPP] sites and centrally reviewed by the LLMPP pathology panel [WHO 2016]; n=121 previously published [PMID: 33225311, 33951889, 34465776, 34714908]), 65 transcriptomes (n=44 new; n=21 published) and 37 in situ single cell transcriptomic profiles (CosMx Spatial Molecular Imager) from archival diagnostic tissue biopsies. Somatic mutations (SNVs/Indels) were identified using an ensemble of four variant callers (Strelka2, Lofreq, Mutect2, SAGE). Salmon and DESeq2 were used to identify differentially expressed genes. This multi-omics dataset was compared to other known B-cell malignancies including 92 MM, 238 Burkitt lymphomas (BL), and 208 DLBCLs. Cell segmentation of the CosMx data was performed using Baysor and downstream analyses were conducted using the Seurat workflow. For functional validation, cell viability assays (CellTiter-Glo Luminescent Assay) were conducted in the PBL cell line, PBL-1, and 4 control DLBCL cell lines. Results Within the cohort, 63% (106/169) of primary PBL cases were EBV-positive (EBV+) and 57% (82/144) harbored MYC rearrangements (MYC+). When stratifying patients by EBV and MYC rearrangement status, mutations in different genes were enriched in each group: STAT3 occurred in 55% (29/53) of EBV+/MYC+ PBLs; NOTCH1 in 19% (7/36) of EBV+/MYC-; MYC in 24% (6/25) and TP53 in 40% (10/25) of EBV-/MYC+ tumors; TET2 was mutated in 38% (9/24) and KRAS in 25% (6/24) of EBV-/MYC- PBLs. EBV-/MYC+ tumors represented a subgroup of patients with dismal outcomes. The 2-year overall survival (OS) of these patients was 22% compared to 61%, 78%, and 54% of EBV+/MYC+, EBV+/MYC-, and EBV-/MYC- PBL patients, respectively (log-rank test p-adj. &lt; 0.05). Consistent with previous studies, we observed recurrent mutations affecting JAK-STAT (STAT3, SOCS1, SOCS3, DUSP2) in 41% of cases and RAS-RAF (NRAS, KRAS, BRAF) signaling in 38% of all PBLs. In contrast to ABC-DLBCL, very few mutations occurred in the NF-κB signalling pathway. Accordingly, PBL showed marked downregulation of genes involved in B-cell receptor and NF-κB signaling. Consistent with the lack of reliance on these pathways, functional analyses in PBL-1 showed resistance to treatment to ibrutinib as well as PI3K- and MALT1-inhibitors. Moreover, constitutive expression of the IκBα super-repressor did not affect viability of PBL-1 cells. In situ single cell transcriptomic data analyses showed a sparse tumor microenvironment (TME) in PBL, with the primary non-malignant cell types being, on average, 10% macrophages, 7% NK/T cells, and 4% stromal cells of all represented cell types. EBV+/MYC+ tumors displayed a more abundant immune cell population with higher levels of macrophages (median 12%) and NK/T cells (median 9%), whereas EBV-/MYC- tumors were composed of the lowest levels of immune cells (median 4% macrophages and 1% NK/T cells). With respect to malignant cell phenotypes, we noted a novel population of SPP1-expressing cells that were enriched in EBV+/MYC+ tumors and a population of CD44-expressing cells that were enriched in EBV+/MYC- tumors. Conclusion Here we present novel subgroups of PBL with unique biology and clinical outcomes. We show that PBL does not rely on B-cell receptor signaling, instead relying on potentially targetable vulnerabilities in JAK-STAT, NOTCH, and RAS-RAF signaling according to EBV positivity and MYC rearrangement status. Lastly, we provide insight into the TME of PBL and demonstrate a novel population of SPP1 and CD44 expressing malignant cells in EBV+ tumors.

Progression of liver disease is dependent on intercellular signaling, including those mediated by extracellular vesicles (EVs). Within these EVs, microRNAs (miRNAs) are packaged to selectively silence gene expression in recipient cells for upregulating or downregulating a specific pathway. Injured hepatocytes secrete EV-associated miRNAs which can be taken up by liver sinusoidal endothelial cells, immune cells, hepatic stellate cells, and other cell types. In addition, these recipient cells will secrete their own EV-associated miRNAs to propagate a response throughout the tissue and the circulation. In this review, we comment on the implications of EV-miRNAs in the progression of alcohol-associated liver disease, metabolic dysfunction-associated steatohepatitis, viral and parasitic infections, liver fibrosis, and liver malignancies. We summarize how circulating miRNAs can be used as biomarkers and the potential of utilizing EVs and miRNAs as therapeutic methods to treat liver disease.

Abstract We investigated the extent of access to Meckel's cave (MC) and the middle cranial fossa (MCF) protecting the internal carotid artery (ICA) using the retrosigmoid approach with endoscopic-assisted reverse anterior petrosectomy (EA-RAP). Five specimens were dissected using the limited and extended EA-RAP. Based on the bone removal of the internal acoustic meatus (IAM) and subarcuate fossa, exposure of the MC and ICA were statistically compared. The limited and extended EA-RAP allowed access to the medial and anterior MC (4 mm posterior to the first genu of the cavernous ICA, and 20 mm posterior to foramen rotundum [FR]). The access to the lateral MC varied with distance of 12 and 8 mm medial to the foramen ovale for the limited and extended EA-RAP, respectively. In the extended EA-RAP, the exposure of the ICA was gained by drilling with the 0-degree endoscope (3 mm) versus 45-degree endoscope (9 mm). The working distances from the midpoint of the IAM to the most medial point of the exposed ICA was 24 mm. The most lateral point of the exposed ICA varied between 0- and 45-degree endoscopes with a distance of 21 and 13 mm, respectively. A coronal plane from the posterior genu of the cavernous ICA and a sagittal plane to the common crus of the semicircular canals can define the area of MCF accessed by the EA-RAP. Drilling of the temporal bone should be carefully customized according to the patient and can be aided by endoscopic assistance for direct visualization to minimize the risk of injuries to ICA.

The field of ribonucleic acid (RNA) biology has revealed an array of noncoding RNA species, particularly long noncoding RNAs (lncRNAs), which play crucial roles in liver disease pathogenesis. This review explores the diverse functions of lncRNAs in liver pathology, including metabolic-associated steatotic liver disease, hepatocellular carcinoma, alcohol-related liver disease, and cholangiopathies such as primary sclerosing cholangitis and cholangiocarcinoma. We highlight key lncRNAs that regulate lipid metabolism, inflammation, fibrosis, and oncogenesis in the liver, demonstrating their diagnostic and therapeutic potential. Emerging RNA-based therapies, such as mRNA therapy, RNA interference, and antisense oligonucleotides, offer approaches to modulate lncRNA activity and address liver disease at a molecular level. Advances in sequencing technologies and bioinformatics pipelines are simultaneously enabling the identification and functional characterization of novel lncRNAs, driving innovation in personalized medicine. In conclusion, this review highlights the potential of lncRNAs as biomarkers and therapeutic targets in liver disease and emphasizes the need for further research into their regulatory mechanisms and clinical applications.