Translational In Vivo Assays in Behavioral Biology.

The failure of preclinical research to advance successful candidate medications in psychiatry has created a paradigmatic crisis in psychiatry. The Research Domain Criteria (RDoC) initiative was designed to remedy this situation with a neuroscience-based approach that employs multimodal and cross-species in vivo methodology to increase the probability of translational findings and, consequently, drug discovery. The present review underscores the feasibility of this methodological approach by briefly reviewing, first, the use of multidimensional and cross-species methodologies in traditional behavioral pharmacology and, subsequently, the utility of this approach in contemporary neuroimaging and electrophysiology research-with a focus on the value of functionally homologous studies in nonhuman and human subjects. The final section provides a brief review of the RDoC, with a focus on the potential strengths and weaknesses of its domain-based underpinnings. Optimistically, this mechanistic and multidimensional approach in neuropsychiatric research will lead to novel therapeutics for the management of neuropsychiatric disorders.

Splicing analysis of 24 potential spliceogenic variants in MMR genes and clinical interpretation based on refined ACMG/AMP criteria.

Lynch syndrome (LS) is a common hereditary cancer syndrome caused by heterozygous germline pathogenic variants in DNA mismatch repair (MMR) genes. Splicing defect constitutes one of the major mechanisms for MMR gene inactivation. Using RT-PCR based RNA analysis, we investigated 24 potential spliceogenic variants in MMR genes and determined their pathogenicity based on refined splicing-related American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria. Aberrant transcripts were confirmed in 19 variants and 17 of which were classified as pathogenic including 11 located outside of canonical splice sites. Most of these variants were previously reported in LS patients without mRNA splicing assessment. Thus, our study provides crucial evidence for pathogenicity determination, allowing for appropriate clinical follow-up. We also found that computational predictions were globally well correlated with RNA analysis results and the use of both SPiP and SpliceAI software appeared more efficient for splicing defect prediction.

Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3/BP4 criteria.

Recommendations from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) for interpreting sequence variants specify the use of computational predictors as "supporting" level of evidence for pathogenicity or benignity using criteria PP3 and BP4, respectively. However, score intervals defined by tool developers, and ACMG/AMP recommendations that require the consensus of multiple predictors, lack quantitative support. Previously, we described a probabilistic framework that quantified the strengths of evidence (supporting, moderate, strong, very strong) within ACMG/AMP recommendations. We have extended this framework to computational predictors and introduce a new standard that converts a tool's scores to PP3 and BP4 evidence strengths. Our approach is based on estimating the local positive predictive value and can calibrate any computational tool or other continuous-scale evidence on any variant type. We estimate thresholds (score intervals) corresponding to each strength of evidence for pathogenicity and benignity for thirteen missense variant interpretation tools, using carefully assembled independent data sets. Most tools achieved supporting evidence level for both pathogenic and benign classification using newly established thresholds. Multiple tools reached score thresholds justifying moderate and several reached strong evidence levels. One tool reached very strong evidence level for benign classification on some variants. Based on these findings, we provide recommendations for evidence-based revisions of the PP3 and BP4 ACMG/AMP criteria using individual tools and future assessment of computational methods for clinical interpretation.

Performance of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Diagnostic Criteria for Infective Endocarditis in Relation to the Modified Duke Criteria and to Clinical Management-Reanalysis of Retrospective Bacteremia Cohorts.

BACKGROUND: Revised diagnostic criteria for infective endocarditis (IE), the 2023 Duke-ISCVID criteria, were recently presented and need validation. Here, we compare the 2000 modified Duke criteria for IE with Duke-ISCVID among patients with bacteremia and relate the diagnostic classification to IE treatment. METHODS: We reanalyzed patient cohorts with Staphylococcus aureus, Staphylococcus lugdunensis, non-ß-hemolytic streptococci, Streptococcus-like bacteria, Streptococcus dysgalactiae, Enterococcus faecalis, and HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) bacteremia. Episodes were classified as definite, possible, or rejected IE with the modified Duke and Duke-ISCVID criteria. Reclassification included the microbiology criteria, positron emission tomography-computed tomography, and cardiac implanted electronic devices. To calculate sensitivity, patients treated for IE were considered as having IE. RESULTS: In 4050 episodes of bacteremia, the modified Duke criteria assigned 307 episodes (7.6%) as definite IE, 1190 (29%) as possible IE, and 2553 (63%) as rejected IE. Using the Duke-ISCVID criteria, 13 episodes (0.3%) were reclassified from possible to definite IE, and 475 episodes (12%) were reclassified from rejected to possible IE. With the modified Duke criteria, 79 episodes that were treated as IE were classified as possible IE, and 11 of these episodes were reclassified to definite IE with Duke-ISCVID. Applying the decision to treat for IE as a reference standard, the sensitivity of the Duke-ISCVID criteria was 80%. None of the 475 episodes reclassified to possible IE were treated as IE. CONCLUSIONS: The Duke-ISCVID criteria reclassified a small proportion of episodes to definite IE at the expense of more episodes of possible IE. Future criteria should minimize the possible IE group while keeping or improving sensitivity.

External Validation of the 2023 Duke-International Society for Cardiovascular Infectious Diseases Diagnostic Criteria for Infective Endocarditis.

BACKGROUND: The 2023 Duke-International Society of Cardiovascular Infectious Diseases (ISCVID) criteria for infective endocarditis (IE) were introduced to improve classification of IE for research and clinical purposes. External validation studies are required. METHODS: We studied consecutive patients with suspected IE referred to the IE team of Amsterdam University Medical Center (from October 2016 to March 2021). An international expert panel independently reviewed case summaries and assigned a final diagnosis of "IE" or "not IE," which served as the reference standard, to which the "definite" Duke-ISCVID classifications were compared. We also evaluated accuracy when excluding cardiac surgical and pathologic data ("clinical" criteria). Finally, we compared the 2023 Duke-ISCVID with the 2000 modified Duke criteria and the 2015 and 2023 European Society of Cardiology (ESC) criteria. RESULTS: A total of 595 consecutive patients with suspected IE were included: 399 (67%) were adjudicated as having IE; 111 (19%) had prosthetic valve IE, and 48 (8%) had a cardiac implantable electronic device IE. The 2023 Duke-ISCVID criteria were more sensitive than either the modified Duke or 2015 ESC criteria (84.2% vs 74.9% and 80%, respectively; P < .001) without significant loss of specificity. The 2023 Duke-ISCVID criteria were similarly sensitive but more specific than the 2023 ESC criteria (94% vs 82%; P < .001). The same pattern was seen for the clinical criteria (excluding surgical/pathologic results). New modifications in the 2023 Duke-ISCVID criteria related to "major microbiological" and "imaging" criteria had the most impact. CONCLUSIONS: The 2023 Duke-ISCVID criteria represent a significant advance in the diagnostic classification of patients with suspected IE.

Evaluation of the HANDOC score and the 2023 ISCVID and ESC Duke clinical criteria for the diagnosis of infective endocarditis among patients with streptococcal bacteremia.

BACKGROUND: Streptococci are a common cause of infective endocarditis (IE). We aimed to evaluate the performance of the HANDOC score to identify patients at high-risk for IE and the Duke clinical criteria of the European Society of Cardiology (ESC; 2015 and 2023 versions) and the 2023 version from the International Society of Cardiovascular Infectious Diseases (ISCVID) in diagnosing IE among patients with streptococcal bacteremia. METHODS: This retrospective study included adult patients with streptococcal bacteremia hospitalized at Lausanne University Hospital. Episodes were classified as IE by the Endocarditis Team. A HANDOC score >2 classified patients as high-risk for IE. RESULTS: Among 851 episodes with streptococcal bacteremia, IE was diagnosed in 171 episodes (20%). Among 607 episodes with non-beta-hemolytic streptococci, 213 (35%) had HANDOC scores >2 points; 132 (22%) had IE. The sensitivity of the HANDOC score to identify episodes at high-risk for IE was 95% (90-98%), the specificity 82% (78-85%), and the NPV 98% (96-99%). 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria classified 114 (13%), 145 (17%), and 126 (15%) episodes as definite IE, respectively. Sensitivity for the 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria was calculated at 65% (57-72%), 81% (74-86%), and 73% (65-79%), respectively, with specificity at 100% (98-100%), 99% (98-100%), and 99% (98-100%), respectively. CONCLUSIONS: The HANDOC score showed an excellent NPV to identify episodes at high-risk for IE. Among the different versions of the Duke criteria, the 2023 Duke-ISCVID version fared better for the diagnosis of IE among streptococcal bacteremia.

Compared Performance of the 2023 Duke-International Society for Cardiovascular Infectious Diseases, 2000 Modified Duke, and 2015 European Society of Cardiology Criteria for the Diagnosis of Infective Endocarditis in a French Multicenter Prospective Cohort.

BACKGROUND: The 2023 Duke-International Society for Cardiovascular Diseases (ISCVID) criteria for infective endocarditis (IE) were proposed as an updated diagnostic classification of IE. Using an open prospective multicenter cohort of patients treated for IE, we compared the performance of these new criteria to that of the 2000 Modified Duke and 2015 European Society of Cardiology (ESC) criteria. METHODS: Cases of patients treated for IE between January 2017 and October 2022 were adjudicated as certain IE or not. Each case was also categorized as either definite or possible/rejected within each classification. Sensitivity, specificity, and accuracy were estimated with 95% confidence intervals. RESULTS: Of the 1194 patients analyzed (mean age, 66.1 years; 71.2% males), 414 (34.7%) had a prosthetic valve and 284 (23.8%) had a cardiac implanted electronic device (CIED); 946 (79.2%) were adjudicated as certain IE; 978 (81.9%), 997 (83.5%), and 1057 (88.5%) were classified as definite IE in the 2000 modified Duke, 2015 ESC, and 2023 Duke-ISCVID criteria, respectively. The sensitivity of each set of criteria was 93.2% (95% confidence interval [CI], 91.6-94.8), 95.0% (95% CI, 93.7-96.4), and 97.6% (95% CI, 96.6-98.6), respectively (P < .001 for all 2-by-2 comparisons). Corresponding specificity rates were 61.3% (95% CI, 55.2-67.4), 60.5% (95% CI, 54.4-66.6), and 46.0% (95% CI, 39.8-52.2), respectively. In patients without CIED, sensitivity rates were 94.8% (95% CI, 93.2-96.4), 96.5% (95% CI, 95.1-97.8), and 97.7% (95% CI, 96.6-98.8); specificity rates were 59.0% (95% CI, 51.6-66.3), 56.6% (95% CI, 49.3-64.0), and 53.8% (95% CI, 46.3-61.2), respectively. CONCLUSIONS: Overall, the 2023 Duke-ISCVID criteria had a significantly higher sensitivity but a significantly lower specificity compared with older criteria. This decreased specificity was mainly attributable to patients with CIED.

Evaluation of the 2023 Duke-ISCVID and 2023 Duke-ESC Clinical Criteria for the Diagnosis of Infective Endocarditis in a Multicenter Cohort of Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: The Duke criteria for infective endocarditis (IE) diagnosis underwent revisions in 2023 by the European Society of Cardiology (ESC) and the International Society for Cardiovascular Infectious Diseases (ISCVID). This study aims to assess the diagnostic accuracy of these criteria, focusing on patients with Staphylococcus aureus bacteremia (SAB). METHODS: This Swiss multicenter study conducted between 2014 and 2023 pooled data from three cohorts. It evaluated the performance of each iteration of the Duke criteria by assessing the degree of concordance between definite S. aureus IE (SAIE) and the diagnoses made by the Endocarditis Team (2018-23) or IE expert clinicians (2014-17). RESULTS: Among 1344 SAB episodes analyzed, 486 (36%) were identified as cases of SAIE. The 2023 Duke-ISCVID and 2023 Duke-ESC criteria demonstrated improved sensitivity for SAIE diagnosis (81% and 82%, respectively) compared to the 2015 Duke-ESC criteria (75%). However, the new criteria exhibited reduced specificity for SAIE (96% for both) compared to the 2015 criteria (99%). Spondylodiscitis was more prevalent among patients with SAIE compared to those with SAB alone (10% vs 7%, P = .026). However, when patients meeting the minor 2015 Duke-ESC vascular criterion were excluded, the incidence of spondylodiscitis was similar between SAIE and SAB patients (6% vs 5%, P = .461). CONCLUSIONS: The 2023 Duke-ISCVID and 2023 Duke-ESC clinical criteria show improved sensitivity for SAIE diagnosis compared to 2015 Duke-ESC criteria. However, this increase in sensitivity comes at the expense of reduced specificity. Future research should aim at evaluating the impact of each component introduced within these criteria.

Cutibacterium species valvular and cardiac device-related infective endocarditis: contemporary data from the GAMES prospective cohort (2008-2023).

BACKGROUND: Information on infective endocarditis (IE) caused by Cutibacterium spp. is limited and new Duke-ISCVID criteria have not yet been properly assessed. We examined clinical characteristics, outcomes and performance of diagnostic tests for Cutibacterium valvular and cardiac implantable electronic device-related IE (CIED-IE). METHODS: Data corresponding to all episodes of Cutibacterium IE recorded from 2008 to 2023 in a prospective national cohort including 46 Spanish hospitals were examined. Possible IE cases were reassessed using the new criteria. The sensitivity of blood cultures, valvular and CIED cultures, and PCR of the 16SrRNA gene and sequencing (16SPCR) was evaluated. RESULTS: There were 67/6,692 (1%) episodes of IE caused by Cutibacterium spp., 85% affecting men. Of these, 50 were valve-related (45 prosthetic, 5 native) and 17 CIED-related. The new criteria identified 8 additional cases and reclassified 15 as definite IE. Intracardiac complications (abscess, pseudoaneurysm, perforation or intracardiac fistula) occurred in 23/50 (46%) valvular IE episodes, leading to 18% mortality, and up to 40% mortality if surgery was indicated but could not be performed. All CIED-IE cases underwent device removal and no deaths were recorded. Positive diagnosis rates for blood cultures, valve/device cultures and 16SPCR were 52%, 70% and 82%, respectively. CONCLUSION: Cutibacterium IE is a rare yet potentially life-threatening condition that warrants a high index of suspicion in men with endovascular prosthetic material. The new Duke-ISCVID criteria and molecular techniques are useful for its diagnosis. Considering a significant complication rate, cardiac surgery and removal of CIEDs play a key role in reducing mortality.

Comparison of the 2015 and 2023 European Society of Cardiology versions of the Duke criteria among patients with suspected infective endocarditis.

BACKGROUND: Diagnosing infective endocarditis (IE) poses a significant challenge. This study aimed to compare the diagnostic accuracy of the 2015 and 2023 Duke clinical criteria introduced by the European Society of Cardiology (ESC) in a cohort of patients suspected of having IE. METHODS: Conducted retrospectively at two Swiss University Hospitals between 2014-2023, the study involved patients with suspected IE. Each hospitals' Endocarditis Team categorized case as either IE or not IE. The performance of each iteration of the Duke-ESC clinical criteria was assessed based on the agreement between definite IE and the diagnoses made by the Endocarditis Team. RESULTS: Among the 3127 episodes with suspected IE, 1177 (38%) were confirmed to have IE. Using the 2015 Duke-ESC clinical criteria, 707 (23%) episodes were deemed definite IE, with 696 (98%) receiving a final IE diagnosis. With the 2023 Duke-ESC clinical criteria, 855 (27%) episodes were classified as definite IE, of which 813 (95%) were confirmed as IE. The 2015 and 2023 Duke-ESC clinical criteria categorized 1039 (33%) and 1034 (33%) episodes, respectively, as possible IE. Sensitivity for the 2015 Duke-ESC and the 2023 Duke-ESC clinical criteria was calculated at 59% (95% CI: 56-62%), and 69% (66-72%), respectively, with specificity at 99% (99-100%), and 98% (97-98%), respectively. CONCLUSIONS: The 2023 ESC criteria demonstrated significant improvements in sensitivity compared to the 2015 version, although one-third of episodes were classified as possible IE by both versions.

Eyes Wide Shut: A Cohort Study Questioning the Role of Fundoscopy in Infective Endocarditis Diagnosis.

In this retrospective/prospective study, we assessed the role of fundoscopy in 711 episodes with suspected infective endocarditis (IE); 238 (33%) had IE. Ocular embolic events (retinal emboli or chorioretinitis/endophthalmitis) and Roth spots were found in 37 (5%) and 34 (5%) episodes, respectively, but had no impact on IE diagnosis.

Evaluation of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Criteria in a Multicenter Cohort of Patients With Suspected Infective Endocarditis.

BACKGROUND: Since publication of Duke criteria for infective endocarditis (IE) diagnosis, several modifications have been proposed. We aimed to evaluate the diagnostic performance of the Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) 2023 criteria compared to prior versions from 2000 (Duke-Li 2000) and 2015 (Duke-ESC [European Society for Cardiology] 2015). METHODS: This study was conducted at 2 university hospitals between 2014 and 2022 among patients with suspected IE. A case was classified as IE (final IE diagnosis) by the Endocarditis Team. Sensitivity for each version of the Duke criteria was calculated among patients with confirmed IE based on pathological, surgical, and microbiological data. Specificity for each version of the Duke criteria was calculated among patients with suspected IE for whom IE diagnosis was ruled out. RESULTS: In total, 2132 episodes with suspected IE were included, of which 1101 (52%) had final IE diagnosis. Definite IE by pathologic criteria was found in 285 (13%), 285 (13%), and 345 (16%) patients using the Duke-Li 2000, Duke-ESC 2015, or the Duke-ISCVID 2023 criteria, respectively. IE was excluded by histopathology in 25 (1%) patients. The Duke-ISCVID 2023 clinical criteria showed a higher sensitivity (84%) compared to previous versions (70%). However, specificity of the new clinical criteria was lower (60%) compared to previous versions (74%). CONCLUSIONS: The Duke-ISCVID 2023 criteria led to an increase in sensitivity compared to previous versions. Further studies are needed to evaluate items that could increase sensitivity by reducing the number of IE patients misclassified as possible, but without having detrimental effect on specificity of Duke criteria.

Genome characteristics and the ODV proteome of a second distinct alphabaculovirus from Spodoptera litura.

BACKGROUND: Spodoptera litura is a harmful pest that feeds on more than 80 species of plants, and can be infected and killed by Spodoptera litura nucleopolyhedrovirus (SpltNPV). SpltNPV-C3 is a type C SpltNPV clone, that was observed and collected in Japan. Compared with type A or type B SpltNPVs, SpltNPV-C3 can cause the rapid mortality of S. litura larvae. METHODS: In this study, occlusion bodies (OBs) and occlusion-derived viruses (ODVs) of SpltNPV-C3 were purified, and OBs were observed by scanning electron microscopy (SEM). ODVs were observed under a transmission electron microscope (TEM). RESULTS: Both OBs and ODVs exhibit morphological characteristics typical of nucleopolyhedroviruses (NPVs).The genome of SpltNPV-C3 was sequenced and analyzed; the total length was 148,634 bp (GenBank accession 780,426,which was submitted as SpltNPV-II), with a G + C content of 45%. A total of 149 predicted ORFs were found. A phylogenetic tree of 90 baculoviruses was constructed based on core baculovirus genes. LC‒MS/MS was used to analyze the proteins of SpltNPV-C3; 34 proteins were found in the purified ODVs, 15 of which were core proteins. The structure of the complexes formed by per os infectivity factors 1, 2, 3 and 4 (PIF-1, PIF-2, PIF-3 and PIF-4) was predicted with the help of the AlphaFold multimer tool and predicted conserved sequences in PIF-3. SpltNPV-C3 is a valuable species because of its virulence, and the analysis of its genome and proteins in this research will be beneficial for pest control efforts.

Prevalence and correlates of diagnosed and probable polycystic ovary syndrome (PCOS) in a cohort of parous women.

OBJECTIVES: To assess correlates of diagnosed and probable polycystic ovary syndrome (PCOS) among parous women. METHODS: This study includes 557 women recruited from multi-specialty clinics in eastern Massachusetts. We categorized women as "diagnosed PCOS" based on medical records and self-reported clinician-diagnoses. Next, we constructed a category of "probable PCOS" for women without a diagnosis but with ≥2 of the following: ovulatory dysfunction (cycle length<21 or ≥35 days), hyperandrogenism (free testosterone>75th percentile), or elevated anti-Müllerian hormone (>75th percentile). We classified the remaining as "no PCOS," and compared characteristics across groups. RESULTS: 9.7% had diagnosed and 9.2% had probable PCOS. The frequency of irregular cycles was similar for diagnosed and probable PCOS. Free testosterone and AMH were higher for probable than diagnosed PCOS. Frequency of irregular cycles and both hormones were higher for the two PCOS groups vs. the no PCOS group. Obesity prevalence for diagnosed PCOS was twice that of probable PCOS (43.9% vs. 19.6%), yet the two groups had similar HbA1c and adiponectin. CONCLUSIONS: Women with probable PCOS are leaner but have comparable glycemic traits to those with a formal diagnosis, highlighting the importance of assessing biochemical profiles among women with irregular cycles, even in the absence of overweight/obesity.

Radiographic and serologic response in patients with unresectable hepatocellular carcinoma receiving systemic antineoplastic treatments: A trial-level analysis.

BACKGROUND: In a disease like unresectable hepatocellular carcinoma, overall survival is an inadequate outcome measure for evaluating the effectiveness of treatments given the high risk of death from liver failure. There is an unmet need for reliable alternative end points for clinical trials and daily clinical practice. To evaluate treatment response in patients with unresectable or metastatic hepatocellular carcinoma (mHCC), imaging-related end points are often used, whereas serologic end points have been developed for patients with serum alpha-fetoprotein levels >20 ng/mL. The objective of this study was to evaluate clinical trials that report concomitant assessment of radiographic and serologic response in patients with mHCC. METHODS: After a systematic review, studies that evaluated response according to radiographic and serologic criteria were selected. A correlation between progression-free survival (PFS) and overall survival (OS) was performed, and a linear regression of each response-related outcome measure with OS was reported. Finally, the effect of eight baseline variables on OS and response-related measures was evaluated. RESULTS: Twenty-six studies were included, including 16 first-line studies and 10 second-line studies. PFS and response rates demonstrated a significant relationship with OS, whereas disease control rates did not. The responses were correlated with OS, particularly in the first-line setting, after targeted therapy, and whenever assessment was early. Among the baseline variables, only performance status had a prognostic role, whereas hepatitis B virus-related liver disease was associated with higher radiographic response rates. CONCLUSIONS: PFS and radiographic and serologic response rates appear to be reliable intermediate end points in patients with mHCC who are undergoing systemic antineoplastic therapy. However, the serologic response is available earlier.

Summary of a consensus conference on heart-liver transplantation.

Patients with severe heart disease may have coexisting liver disease from various causes. The incidence of combined heart-liver transplant (CHLT) is increasing as more patients with congenital heart disease survive to adulthood and develop advanced heart failure with associated liver disease from chronic right-sided heart or Fontan failure. However, the criteria for CHLT have not been established. To address this unmet need, a virtual consensus conference was organized on June 10, 2022, endorsed by the American Society of Transplantation. The conference represented a collaborative effort by experts in cardiothoracic and liver transplantation from across the United States to assess interdisciplinary criteria for liver transplantation in the CHLT candidate, surgical considerations of CHLT, current allocation system that generally results in the liver following the heart for CHLT, and optimal post-CHLT management. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical issues related to multiorgan transplantation were also debated. The findings and consensus statements are presented.

Unique report of iliocaval endovascular reconstruction successfully enabling a kidney transplant.

Patients with end-stage renal disease and iliocaval venous obstruction are normally nonviable recipients of kidney transplantation. We report a case of a 34-year-old male patient who has been receiving hemodialysis as renal replacement therapy for 6 years due to immunoglobulin A nephropathy. Past medical history included multiple central venous catheter infections and catheter-associated thrombosis. Iliac confluence and inferior vena cava occlusion previously excluded the patient from the renal transplantation list. The exhaustion of venous access sites was already documented. After multidisciplinary discussion, the patient was proposed for endovascular iliocaval reconstruction aiming for a future kidney transplant. Iliocaval recanalization was achieved through bilateral femoral access. Inferior vena cava and iliac angioplasty were performed. A dedicated venous stent was deployed in the inferior vena cava, followed by a double-barrel reconstruction of the iliac confluence. Successful iliocaval recanalization was accomplished. Five months after kidney transplantation was performed with a deceased donor graft in the right iliac fossa. The postoperative period was uneventful. After 12 months, the patient remained free from kidney replacement therapies with a serum creatinine level of 1.3 mg/dL. To the best of our knowledge, this is the first clinical description of a successful kidney transplant in a patient with a previous iliocaval reconstruction.

Liver machine perfusion technology: Expanding the donor pool to improve access to liver transplantation.

The imbalance between organ supply and demand continues to limit the broader benefits of organ transplantation. Machine perfusion (MP) may increase the supply of donor livers by expanding the use of extended-criteria donors. Using the United Network for Organ Sharing/Organ Procurement and Transplantation Network and the Standard Transplant Analysis and Research dataset, we reviewed the effect of MP implementation on the behavior of transplant centers. We identified 15 high-utilizing MP centers that were matched to suitable controls based on volume and geographical proximity. We conducted a differences-in-differences analysis using linear regression to estimate the impact of MP adoption on the transplant centers' donor utilization. We found a significant increase in cold ischemia time and organs with donor warm ischemia time over 30 minutes (P < .05). After removing one outlier center, the analysis showed that these centers through MP accepted overall more donation after circulatory death donors, donation after circulatory death donors over 50 years old, donors with macrovesicular steatosis greater than 30% on liver biopsy, and donor warm ischemia time over 30 minutes (P < .05). MP has allowed centers to expand their use of extended-criteria donors beyond traditional cutoffs and to increase patient access to liver transplantation.

Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Recently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Concern remains regarding whether the evidence generated under the NAFLD definition can be used for MASLD. We compared the clinical profile and outcomes of NAFLD to MASLD using tertiary care- and population-based data. METHODS: Comparison data were obtained from our NAFLD database and the National Health and Nutrition Examination Survey (NHANES III). Clinical profiles and non-invasive tests (enhanced liver fibrosis [ELF] score, fibrosis-4 index [FIB-4] and vibration-controlled transient elastography) were compared. Mortality data were obtained from NHANES-National Death Index. All-cause mortality was assessed by Cox proportional hazards regression models and cause-specific mortality by competing risk analysis. RESULTS: There were 6,429 patients in the NAFLD database (age: 54 ± 12 years, 42% male, BMI 35.4 ± 8.3, waist circumference 112 ± 17 cm, 52% type 2 diabetes). Average scores for ELF, FIB-4 and liver stiffness were 9.6 ± 1.2, 1.69 ± 1.24,14.0 ± 11.8 kPa, respectively; 99% met MASLD criteria; 95% met MASLD on BMI only. Predictive accuracy of ELF and FIB-4 were identical between MASLD and NAFLD. We included 12,519 eligible participants from NHANES (age 43.00 years, 47.38% male, 22.70% obese, 7.28% type 2 diabetes, 82.51% ≥1 cardiometabolic criteria). Among the NHANES study population, there was excellent concordance between MASLD and NAFLD diagnoses: Cohen's kappa coefficient: 0.968 (95% CI 0.962-0.973) with 5.29% of NAFLD cases not meeting MASLD criteria. After a median follow-up of 22.83 years, there were no mortality differences between MASLD and NAFLD diagnoses (p values ≥0.05). CONCLUSIONS: NAFLD and MASLD are similar except individuals with MASLD seem to be older with slightly higher mortality risk, likely owing to cardiometabolic risk factors. Clinical profiles and non-invasive test thresholds were also identical. These data provide evidence that NAFLD and MASLD terminologies can be used interchangeably. For the small proportion of patients with NAFLD who do not meet MASLD criteria, further consideration is needed. IMPACT AND IMPLICATIONS: In June 2023, new terminology (MASLD) was adopted to replace the term NAFLD as a means to better describe what the liver disease is rather than what it is not, as well as to potentially reduce stigma. Given that MASLD requires at least one cardiometabolic risk factor, questions were raised as to whether this change in the definition would nullify the similarities between NAFLD and MASLD and require new evidence to be generated for MASLD. We used our NAFLD database and a US population-based database to show that the vast majority of patients with NAFLD fulfill criteria for MASLD. Non-invasive tests performed similarly in both groups. Mortality risk was slightly higher in those with MASLD, which is attributed to the presence of cardiometabolic risks. These results provide evidence that data generated in the past three decades for NAFLD can be used interchangeably for MASLD.

Non-criteria antiphospholipid antibodies and calprotectin as potential biomarkers in pediatric antiphospholipid syndrome.

Our study aimed to evaluate the presence, clinical associations, and potential mechanistic roles of non-criteria antiphospholipid antibodies (aPL) and circulating calprotectin, a highly stable marker of neutrophil extracellular trap release (NETosis), in pediatric APS patients. We found that 79% of pediatric APS patients had at least one non-criteria aPL at moderate-to-high titer. Univariate logistic regression demonstrated that positive anti-beta-2 glycoprotein I domain 1 (anti-D1) IgG (p = 0.008), anti-phosphatidylserine/prothrombin (aPS/PT) IgG (p < 0.001), and aPS/PT IgM (p < 0.001) were significantly associated with venous thrombosis. Positive anti-D1 IgG (p < 0.001), aPS/PT IgG (p < 0.001), and aPS/PT IgM (p = 0.001) were also associated with non-thrombotic manifestations of APS, such as thrombocytopenia. Increased levels of calprotectin were detected in children with APS. Calprotectin correlated positively with absolute neutrophil count (r = 0.63, p = 0.008) and negatively with platelet count (r = -0.59, p = 0.015). Mechanistically, plasma from pediatric APS patients with high calprotectin levels impaired platelet viability in a dose-dependent manner.