Low preoperative serum uric acid is associated with early acute kidney injury after living donor liver transplantation.

BACKGROUND: Liver transplantation is treatment option for patients with end stage liver disease and hepatocellular carcinoma. Renal function deterioration significantly impacts the survival rates of liver recipients, and serum uric acid (SUA) is associated with both acute and chronic renal function disorders. Thus, our study aimed to assess the relationship and predictive value of preoperative SUA level and postoperative acute kidney injury (AKI) in living donor liver transplantation (LDLT). METHODS: We conducted a prospective observational study on 87 patients undergoing LDLT. Blood samples were collected immediately prior to LDLT, and renal function status was followed up for 3 consecutive days postoperatively. RESULTS: Low SUA levels (cutoff value 4.15 mg/dL) were associated with a high risk of early post-transplantation AKI. The area under the curve was 0.73 (sensitivity, 79.2%; specificity, 59.4%). Although not statistically significant, there were no deaths in the non-AKI group but two in the early AKI group secondary to liver graft dysfunction in addition to early AKI within the first month after LDLT. CONCLUSION: AKI after liver transplantation may lead to a deterioration of patient status and increased mortality rates. We determined low preoperative SUA levels as a possible risk factor for early postoperative AK.

Protein phosphatase 6 activates NF-κB to confer sensitivity to MAPK pathway inhibitors in KRAS- and BRAF-mutant cancer cells.

The Ras-mitogen-activated protein kinase (MAPK) pathway is a major target for cancer treatment. To better understand the genetic pathways that modulate cancer cell sensitivity to MAPK pathway inhibitors, we performed a CRISPR knockout screen with MAPK pathway inhibitors on a colorectal cancer (CRC) cell line carrying mutant KRAS. Genetic deletion of the catalytic subunit of protein phosphatase 6 (PP6), encoded by PPP6C, rendered KRAS- and BRAF-mutant CRC and BRAF-mutant melanoma cells more resistant to these inhibitors. In the absence of MAPK pathway inhibition, PPP6C deletion in CRC cells decreased cell proliferation in two-dimensional (2D) adherent cultures but accelerated the growth of tumor spheroids in 3D culture and tumor xenografts in vivo. PPP6C deletion enhanced the activation of nuclear factor κB (NF-κB) signaling in CRC and melanoma cells and circumvented the cell cycle arrest and decreased cyclin D1 abundance induced by MAPK pathway blockade in CRC cells. Inhibiting NF-κB activity by genetic and pharmacological means restored the sensitivity of PPP6C-deficient cells to MAPK pathway inhibition in CRC and melanoma cells in vitro and in CRC cells in vivo. Furthermore, a R264 point mutation in PPP6C conferred loss of function in CRC cells, phenocopying the enhanced NF-κB activation and resistance to MAPK pathway inhibition observed for PPP6C deletion. These findings demonstrate that PP6 constrains the growth of KRAS- and BRAF-mutant cancer cells, implicates the PP6-NF-κB axis as a modulator of MAPK pathway output, and presents a rationale for cotargeting the NF-κB pathway in PPP6C-mutant cancer cells.

Regulatory safeguards needed if preimplantation genetic testing for polygenic risk scores (PGT-P) is permitted in Singapore.

Singapore, a highly affluent island city-state located in Southeast Asia, has increasingly leveraged new assisted reproductive technologies (ART) to overcome its dismal fertility rates in recent years. A new frontier in ART is preimplantation genetic testing (PGT) for polygenic risk scores (PRS) to predict complex multifactorial traits in IVF (in vitro fertilisation) embryos, such as type 2 diabetes, cardiovascular diseases and various other characteristics like height, intelligence quotient (IQ), hair and eye colour. Unlike well-known safety risks with human genome editing, there are negligible risks with PGT-P, because there are no man-made genetic modifications that can be transmitted to future generations. Nevertheless, the current efficacy of using PGT-P to select IVF embryos for either increased or decreased probability of developing specific polygenic traits is still far from certain. Hence, the regulatory safeguards proposed here will be based on the assumption that the efficacy of this new technology platform has already been validated. These include: (1) restricting the application of PGT-P only for prevention of clinically relevant polygenic disease traits, (2) securely blocking patients' access to the raw genomic DNA sequencing data of their IVF embryos, (3) validating diagnosis of polygenic disease traits in the prospective parents/grandparents of IVF embryos, and restricting PGT-P only for preventing specifically diagnosed polygenic disease traits and (4) mandating rigorous and comprehensive genetic counselling for IVF patients considering PGT-P. There is an urgent and dire need to prevent abuse of the PGT-P technique, as well as protect the interests and welfare of patients if its clinical application is to be permitted in the country.

A Guiding Model for Undergraduate Medical Education Well-Being Programs.

ABSTRACT: Most medical schools have instituted undergraduate medical education (UME) well-being programs in recent years in response to high rates of medical student distress, but there is currently significant variability in the structure of UME well-being programs and limited guidance on how to best structure such programs to achieve success. In this article, the authors, all leaders of medical student well-being programs at their home institutions and members of the Association of American Medical Colleges Group on Student Affairs Committee on Student Affairs Working Group on Medical Student Well-Being between 2019 and 2023, offer guidance to the national community on how best to structure a UME well-being program. They use the current literature and their professional experiences leading well-being efforts at 7 different institutions to review the case for addressing medical student well-being, propose a guiding model, and make recommendations for strategies to implement this model.The proposed guiding model emphasizes the importance of the learning environment and efficiency of learning to medical student well-being, as well as personal resilience. Based on this model, the authors recommend specific and tangible well-being strategies to implement systemic interventions to improve the learning environment, efficiency of learning, and personal resilience, including: formalizing the well-being program; hiring qualified, dedicated, and empowered well-being leadership with clear responsibilities; acting as a central hub for resources and as a liaison with mental health care; and establishing robust program evaluation methods.

Economic Evaluation of Nirmatrelvir/Ritonavir Among Adults Against Hospitalization During the Omicron Dominated Period in Malaysia: A Real-World Evidence Perspective.

BACKGROUND AND OBJECTIVES: Nirmatrelvir/ritonavir was administered orally to manage mild to moderate symptoms of COVID-19 in adult patients. The objectives of this study were to (i) evaluate the cost-effectiveness of prescribing nirmatrelvir/ritonavir within 5 days of a COVID-19 illness in order to avert hospitalization within a 30-day period in the Malaysia setting; (ii) determine how variations in pricing and hospitalization rates will affect the cost-effectiveness of nirmatrelvir/ritonavir. METHODS: The 30-day hospitalization related to COVID-19 was determined using 1 to 1 propensity score-matched real-world data in Malaysia from 14 July 2022 to 14 November 2022. To determine the total per-person costs related to COVID-19, we added the cost of drug (nirmatrelvir/ritonavir or control), clinic visits and inpatient care. Incremental cost-effectiveness ratio (ICER) per hospitalization averted was calculated. RESULTS: Our cohort included 31,487 patients. The rate of hospitalization within 30 days was found to be 0.35% for the group treated with nirmatrelvir/ritonavir, and 0.52% for the control group. The nirmatrelvir/ritonavir group cost an additional MYR 1,625.72 (USD 358.88) per patient. This treatment also resulted in a reduction of 0.17% risk for hospitalization, which corresponded to an ICER of MYR 946,801.26 (USD 209,006.90) per hospitalization averted. CONCLUSION: In Malaysia, where vaccination rates were high, nirmatrelvir/ritonavir has been shown to be beneficial in the outpatient treatment of adults with COVID-19 who have risk factors; however, it was only marginally cost effective against hospitalization for healthy adults during the Omicron period.

Row Transmission for High Volume-Rate Ultrasound Imaging with a Matrix Array.

The widely used Vermon 1024-element matrix array for three-dimensional (3D) ultrasound imaging has three blank rows in the elevational direction, which breaks the elevation periodicity, thus degrading volumetric image quality. To bypass the blank rows in elevation while maintaining the steering capability in azimuth, we proposed a row transmission (RT) scheme to improve 3D spatial resolution. Specifically, we divided the full array into four apertures, each with multiple rows along the elevation. Each multi-row aperture (MRA) was further divided into subapertures to transmit diverging waves sequentially. Coherent diverging wave compounding (CDWC) was realized in azimuth, while the elevation was multi-element synthetic aperture (M-SA) imaging by regarding each row as an array of dashed line elements. An in-house spatiotemporal coding strategy, cascaded synthetic aperture (CaSA), was incorporated into the RT scheme as RT-CaSA to increase the signal-to-noise ratio (SNR). We compared the proposed RT with conventional bank-by-bank transmission-reception (Bank) and sparse-random-aperture compounding (SRAC) in a wire phantom and the in vivo human abdominal aorta to assess the performance of anatomical imaging and aortic wall motion estimation. Phantom results demonstrated superior lateral resolution achieved by our RT scheme (+19.52% and +16.88% versus Bank, +15.32% and +19.72% versus SRAC, in the azimuth-depth and elevation-depth planes, respectively). Our RT-CaSA showed excellent contrast ratios (+8.19dB and +8.08dB versus Bank, +6.81dB and +5.85dB versus SRAC, +0.99dB and +0.90dB versus RT) and the highest in vivo aortic wall motion estimation accuracy. The RT scheme was demonstrated to have potential for various matrix array-based 3D imaging research.

Carbohydrate-Mediated Pregnancy Gut Microbiota and Neonatal Low Birth Weight.

The effects of gut microbiota on the association between carbohydrate intake during pregnancy and neonatal low birth weight (LBW) were investigated. A prospective cohort study was conducted with 257 singleton-born mother-child pairs in Taiwan, and maternal dietary intake was estimated using a questionnaire, with each macronutrient being classified as low, medium, or high. Maternal fecal samples were collected between 24 and 28 weeks of gestation, and gut microbiota composition and diversity were profiled using 16S rRNA amplicon gene sequencing. Carbohydrates were the major source of total energy (56.61%), followed by fat (27.92%) and protein (15.46%). The rate of infant LBW was 7.8%, which was positively correlated with maternal carbohydrate intake. In the pregnancy gut microbiota, Bacteroides ovatus and Dorea spp. were indirectly and directly negatively associated with fetal growth, respectively; Rosenburia faecis was directly positively associated with neonatal birth weight. Maternal hypertension during pregnancy altered the microbiota features and was associated with poor fetal growth. Microbiota-accessible carbohydrates can modify the composition and function of the pregnancy gut microbiota, thus providing a potential marker to modulate deviations from dietary patterns, particularly in women at risk of hypertension during pregnancy, to prevent neonatal LBW.

Impact of Transgenerational Nutrition on Nonalcoholic Fatty Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and Immunity.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent pediatric liver disorder, primarily attributed to dietary shifts in recent years. NAFLD is characterized by the accumulation of lipid species in hepatocytes, leading to liver inflammation that can progress to steatohepatitis, fibrosis, and cirrhosis. Risk factors contributing to NAFLD encompass genetic variations and metabolic disorders such as obesity, diabetes, and insulin resistance. Moreover, transgenerational influences, resulting in an imbalance of gut microbial composition, epigenetic modifications, and dysregulated hepatic immune responses in offspring, play a pivotal role in pediatric NAFLD development. Maternal nutrition shapes the profile of microbiota-derived metabolites in offspring, exerting significant influence on immune system regulation and the development of metabolic syndrome in offspring. In this review, we summarize recent evidence elucidating the intricate interplay between gut microbiota, epigenetics, and immunity in fetuses exposed to maternal nutrition, and its impact on the onset of NAFLD in offspring. Furthermore, potential therapeutic strategies targeting this network are also discussed.

Specialized connectivity of molecular layer interneuron subtypes leads to disinhibition and synchronous inhibition of cerebellar Purkinje cells.

Molecular layer interneurons (MLIs) account for approximately 80% of the inhibitory interneurons in the cerebellar cortex and are vital to cerebellar processing. MLIs are thought to primarily inhibit Purkinje cells (PCs) and suppress the plasticity of synapses onto PCs. MLIs also inhibit, and are electrically coupled to, other MLIs, but the functional significance of these connections is not known. Here, we find that two recently recognized MLI subtypes, MLI1 and MLI2, have a highly specialized connectivity that allows them to serve distinct functional roles. MLI1s primarily inhibit PCs, are electrically coupled to each other, fire synchronously with other MLI1s on the millisecond timescale in vivo, and synchronously pause PC firing. MLI2s are not electrically coupled, primarily inhibit MLI1s and disinhibit PCs, and are well suited to gating cerebellar-dependent behavior and learning. The synchronous firing of electrically coupled MLI1s and disinhibition provided by MLI2s require a major re-evaluation of cerebellar processing.

The Epidemiology, Management and Therapeutic Outcomes of Subdural Empyema in Neonates with Acute Bacterial Meningitis.

Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels (p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes.

Racial Disparities in Selected Complications and Comorbidities among People with Type 2 Diabetes.

Type 2 diabetes (T2D) is a growing public health concern, disproportionately impacting racial and ethnic minorities. Assessing disparities is the first step towards achieving the translation goal to reduce disparities in diabetes outcomes, according to the Centers for Disease Control and Prevention (CDC)'s Division of Diabetes. We analyzed the data of patients (18+ years) diagnosed with T2D between 1 January 2012 and 31 March 2017, using the electronic health records of the University of Texas Medical Branch at Galveston. We compared the crude rate and age-standardized rate (using direct method) of selected micro- and macrovascular complication rates, associated obesity, and insulin dependence among racial and ethnic groups. Our sample included 20,680 patients who made 394,106 visits (9922 non-Hispanic White patients, 4698 non-Hispanic Black patients, and 6060 Hispanic patients). Our results suggest a higher risk of acquiring macrovascular (hypertension, ischemic disease, and stroke) and microvascular (renal, ophthalmic, and neurological) complications in Black patients compared to non-Hispanic White and Hispanic patients. The rates of stage I or II obesity were higher in Black patients compared with White and Hispanic patients. The rates of insulin use rather than oral hypoglycemics were also higher in Black patients than White and Hispanic patients. The disparities in terms of the higher susceptibility to complications among Black patients are possibly linked to the socioeconomic disadvantages of this population, leading to poorer management. Prevention strategies are warranted to reduce the incidence of T2D complications in racial minorities.

The use of interventional procedures for cancer pain. A brief review.

CONTEXT: Pain is a common experience in people living with cancer. Concerns around opioid prescribing have seen a move toward a multi-modality management approach, which includes interventional pain procedures. PURPOSE: In this paper we discuss the interventional pain procedures used to treat cancer pain at two major tertiary centers in Australia. METHODS AND RESULTS: This expert review provides practical insights on cancer pain management from healthcare providers in different specialties. These insights can be used to guide the management of a wide range of cancer pain types. CONCLUSIONS: Furthermore, this review identifies the need for a systematic and comprehensive approach to the management of cancer pain that is broader than that of a single specialty. With recent advances in pain management procedures, an interdisciplinary approach is essential in order to provide an up to date, patient tailored approach to pain management. This review will help inform the development of a cancer pain intervention registry.

Development of a zinc chloride-based chemo-mechanical system for potential minimally invasive dental caries removal system.

Background/purpose: The chemo-mechanical caries-removal technique is known to offer advantages of selective dentin caries treatment while leaving healthy dental tissues intact. However, current sodium hypochlorite based reagents usually excessively damage dentin collagen. Therefore, the purpose of this study was to develop a novel chemo-mechanical caries-removal system to preserve the collagen network for subsequent prosthetic restorations. Materials and methods: The calfskin-derived collagen was chosen as a model system to investigate the dissolution behavior of collagen under different operating conditions of chemical-ultrasonic treatment systems. The molecular weight, triple-helix structure, the morphology, and functional group of collagen after treatment were investigated. Results: Various concentrations of sodium hypochlorite or zinc chloride together with ultrasonic machinery were chosen to investigate. The outcomes of circular dichroism (CD) spectra demonstrated stability of the triple-helix structure after treatment of a zinc chloride solution. In addition, two apparent bands at molecular weights (MWs) of 130 and 121 kDa evidenced the stability of collagen network. The positive 222 nm and 195 nm negative CD absorption band indicated the existence of a triple-helix structure for type I collagen. The preservation of the morphology and functional group of the collagen network on the etched dentin surface were investigated by in vitro dentin decalcification model. Conclusion: Unlike NaOCl, the 5 wt% zinc chloride solution combined with ultra-sonication showed dissolution rather than denature as well as degradation of the dentin collagen network. Additional in vivo evaluations are needed to verify its usefulness in clinical applications.

Establishing a novel deep learning model for detecting peri-implantitis.

BACKGROUND/PURPOSE: The diagnosis of peri-implantitis using periapical radiographs is crucial. Recently, artificial intelligence may apply in radiographic image analysis effectively. The aim of this study was to differentiate the degree of marginal bone loss of an implant, and also to classify the severity of peri-implantitis using a deep learning model. MATERIALS AND METHODS: A dataset of 800 periapical radiographic images were divided into training (n = 600), validation (n = 100), and test (n = 100) datasets with implants used for deep learning. An object detection algorithm (YOLOv7) was used to identify peri-implantitis. The classification performance of this model was evaluated using metrics, including the specificity, precision, recall, and F1 score. RESULTS: Considering the classification performance, the specificity was 100%, precision was 100%, recall was 94.44%, and F1 score was 97.10%. CONCLUSION: Results of this study suggested that implants can be identified from periapical radiographic images using deep learning-based object detection. This identification system could help dentists and patients suffering from implant problems. However, more images of other implant systems are needed to increase the learning performance to apply this system in clinical practice.

Efficacy of aerobic and resistance exercises on cancer pain: A meta-analysis of randomised controlled trials.

Purpose: To evaluate effects of aerobic and resistance exercises for cancer-related pain in adults with and surviving cancer. Secondary objectives were to a) evaluate the effect of exercise on fatigue, psychological function, physical function, b) assess fidelity to exercise. Design: A systematic search of MEDLINE, EMBASE, AMED, CINAHL and Cochrane Central Register of Controlled Trials was conducted to identify randomised controlled trials (RCTs) comparing aerobic and/or resistance exercise to control groups. The primary endpoint were changes in cancer-related pain intensity from baseline to post intervention. Meta-regression analysis evaluated predictors for heterogeneity between study findings. Tolerability was defined as reporting of exercise-induced adverse events while fidelity evaluated by reported intervention dropout. Results: Twenty-three RCTs including 1954 patients (age 58 ± 8.5 years; 78 % women); 1087 (56 %) and 867 (44 %) allocated to aerobic/resistance exercise therapy and control group, respectively. Exercise therapy was associated with small to moderate decreases in cancer-related pain compared to controls (SMD = 0.38, 95 % CI: 0.17, 0.58). Although there was significant heterogeneity between individual and pooled study effects (Q = 205.25, p < 0.0001), there was no publication bias. Meta-regression including supervision, age, duration and exercise type as moderators showed no significant differences in reported outcomes. Analysis of secondary outcomes revealed a moderate effect for improvements in physical function, fatigue and psychological symptoms. Conclusions: Aerobic and resistance exercises are tolerable and effective adjunct therapies to reduce cancer-related pain while also improving physical function, fatigue and mood. Future RCTs of dose, frequency, compliance and exercise type in specific cancer settings are required.

Technical Variations and Considerations around OAGB in IFSO-APC and IFSO-MENAC Chapters, an Expert Survey.

OBJECTIVE: This study aimed to evaluate the technical variations of one-anastomosis gastric bypass (OAGB) among IFSO-APC and MENAC experts. BACKGROUND: The multitude of technical variations and patient selection challenges among metabolic and bariatric surgeons worldwide necessitates a heightened awareness of these issues. Understanding different perspectives and viewpoints can empower surgeons performing OAGB to adapt their techniques, leading to improved outcomes and reduced complications. METHODS: The scientific team of IFSO-APC, consisting of skilled bariatric and metabolic surgeons specializing in OAGB, conducted a confidential online survey. The survey aimed to assess technical variations and considerations related to OAGB within the IFSO-APC and IFSO-MENAC chapters. A total of 85 OAGB experts participated in the survey, providing their responses through a 35-question online format. The survey took place from January 1, 2024, to February 15, 2024. RESULTS: Most experts do not perform OAGB for children and adolescents younger than 18 years. Most experts create the gastric pouch over a 36-40-F bougie and prefer to create a gastrojejunostomy, at the posterior wall of the gastric pouch. An anti-reflux suture during OAGB is performed in all patients by 51.8% of experts. Most experts set a common limb length of > 4 m in revisional and conversional OAGBs to prevent nutritional complications. CONCLUSION: The ongoing debate among metabolic and bariatric surgeons regarding the technical variations and patient selection in OAGB remains a significant point of discussion. This survey demonstrated the variations in technical aspects and patient selection for OAGB among MBS surgeons in the IFSO-APC and IFSO-MENAC chapters. Standardizing the OAGB technique is crucial to ensure optimal safety and efficacy in this procedure.

Different Splice Isoforms of Peripheral Triggering Receptor Expressed on Myeloid Cells 2 mRNA Expressions are Associated With Cognitive Decline in Mild Dementia Due to Alzheimer's Disease and Reflect Central Neuroinflammation.

Triggering receptor expressed on myeloid cells 2 (TREM2) is upregulated in activated microglia and may be related to cognitive decline in patients with Alzheimer's disease (AD). There is conflicting evidence regarding the association of peripheral TREM2 mRNA expression/soluble TREM2 (the extracellular domain of TREM2) with cognitive function/neuroinflammation in patients with AD. Herein, we studied the TREM2 and TREM2alt mRNA expression and their association with the cognitive performance in subjects with mild dementia due to AD and healthy controls. In a subgroup of patients with AD, magnetic resonance spectroscopy was used to measure the myo-inositol level in the posterior cingulate cortex, a surrogate marker for neuroinflammation. The results showed that increased TREM2 and TREM2alt mRNA expression is associated with AD pathogenesis at the mild dementia stage, thereby serving as a potential biomarker for early symptomatic stage of AD. TREM2 may exert protective effects on both cognition and central neuroinflammation.

Hope for vascular cognitive impairment: Ac-YVAD-cmk as a novel treatment against white matter rarefaction.

Vascular cognitive impairment (VCI) is the second leading cause of dementia with limited treatment options, characterised by cerebral hypoperfusion-induced white matter rarefaction (WMR). Subcortical VCI is the most common form of VCI, but the underlying reasons for region susceptibility remain elusive. Recent studies employing the bilateral cortical artery stenosis (BCAS) method demonstrate that various inflammasomes regulate white matter injury and blood-brain barrier dysfunction but whether caspase-1 inhibition will be beneficial remains unclear. To address this, we performed BCAS on C57/BL6 mice to study the effects of Ac-YVAD-cmk, a caspase-1 inhibitor, on the subcortical and cortical regions. Cerebral blood flow (CBF), WMR, neuroinflammation and the expression of tight junction-related proteins associated with blood-brain barrier integrity were assessed 15 days post BCAS. We observed that Ac-YVAD-cmk restored CBF, attenuated BCAS-induced WMR and restored subcortical myelin expression. Within the subcortical region, BCAS activated the NLRP3/caspase-1/interleukin-1beta axis only within the subcortical region, which was attenuated by Ac-YVAD-cmk. Although we observed that BCAS induced significant increases in VCAM-1 expression in both brain regions that were attenuated with Ac-YVAD-cmk, only ZO-1 and occludin were observed to be significantly altered in the subcortical region. Here we show that caspase-1 may contribute to subcortical regional susceptibility in a mouse model of VCI. In addition, our results support further investigations into the potential of Ac-YVAD-cmk as a novel treatment strategy against subcortical VCI and other conditions exhibiting cerebral hypoperfusion-induced WMR.

The utility of endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TBMC) for the diagnosis of mediastinal lymphoma.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a revolutionary tool for the diagnosis and staging of mediastinal disorders. Nevertheless, its diagnostic capability is reduced in certain disorders such as lymphoproliferative diseases. EBUS-guided transbronchial mediastinal cryobiopsy (EBUS-TBMC) is a novel technique that can provide larger samples with preserved tissue architecture, with an acceptable safety profile. In this case report, we present a middle-aged gentleman with a huge anterior mediastinal mass and bilateral mediastinal and hilar lymphadenopathy. He underwent EBUS-TBNA with rapid on-site evaluation (ROSE) followed by EBUS-TBMC, all under general anaesthesia. Histopathological analysis showed discordance between EBUS-TBNA and EBUS-TBMC in which only TBMC samples provided adequate tissue to attain a diagnosis of primary mediastinal large B-cell lymphoma. This case report reinforced the diagnostic role of EBUS-TBMC in the diagnosis of lymphoproliferative diseases.