Pseudotumoral calcinosis of the elbow with ulnar and radial nerve deficits.

We report here a rare case of an acute peripheral nerve compression by pseudotumoral calcinosis (PCT) at the right elbow in a patient with severe tertiary hyperaparathyroidism. This complication required urgent multidisciplinary management. Surgical decompression by PCT resection enabled rapid motor and sensory recovery.

AMH protects the ovary from doxorubicin by regulating cell fate and the response to DNA damage.

Anti-Müllerian hormone (AMH) protects the ovarian reserve from chemotherapy, and this effect is most pronounced with Doxorubicin (DOX). However, the mechanisms of DOX toxicity and AMH rescue in the ovary remain unclear. Herein, we characterize these mechanisms in various ovarian cell types using scRNAseq. In the mesenchyme, DOX activates the intrinsic apoptotic signaling pathway through p53 class mediators, particularly affecting theca progenitors, while co-treament with AMH halts theca differentiation and reduces apoptotic gene expression. In preantral granulosa cells, DOX upregulates the cell cycle inhibitor Cdkn1a and dysregulates Wnt signaling, which are ameliorated by AMH co-treatment. Finally, in follicles, AMH induces Id3 , a protein involved in DNA repair, which is necessary to prevent the accumulation of DNA lesions marked by γ-H2AX in granulosa cells. Altogether this study characterizes cell, and follicle stage-specific mechanisms of AMH protection of the ovary, offering promising new avenues for fertility preservation in cancer patients undergoing chemotherapy. Highlights: Doxorubicin treatment induces DNA damage that activates the p53 pathway in stromal and follicular cells of the ovary.AMH inhibits the proliferation and differentiation of theca and granulosa cells and promotes follicle survival following Doxorubicin insult.AMH treatment mitigates Doxorubicin-induced DNA damage in the ovary by preventing the accumulation of γ-H2AX-positive unresolved foci, through increased expression of ID3, a protein involved in DNA repair.

Lysosomal exocytosis: From cell protection to protumoral functions.

Lysosomes are single membrane bounded group of acidic organelles that can be involved in a process called lysosomal exocytosis which leads to the extracellular release of their content. Lysosomal exocytosis is required for plasma membrane repair or remodeling events such as bone resorption, antigen presentation or mitosis, and for protection against toxic agents such as heavy metals. Recently, it has been showed that to fulfill this protective role, lysosomal exocytosis needs some autophagic proteins, in an autophagy-independent manner. In addition to these crucial physiological roles, lysosomal exocytosis plays a major protumoral role in various cancers. This effect is exerted through tumor microenvironment modifications, including extracellular matrix remodeling, acidosis, oncogenic and profibrogenic signals. This review provides a comprehensive overview of the different elements released in the microenvironment during lysosomal exocytosis, i.e. proteases, exosomes, and protons, and their effects in the context of tumor development and treatment.

Joint modeling of monocyte HLA-DR expression trajectories predicts 28-day mortality in severe SARS-CoV-2 patients.

The recent SarsCov2 pandemic has disrupted healthcare system notably impacting intensive care units (ICU). In severe cases, the immune system is dysregulated, associating signs of hyperinflammation and immunosuppression. In the present work, we investigated, using a joint modeling approach, whether the trajectories of cellular immunological parameters were associated with survival of COVID-19 ICU patients. This study is based on the REA-IMMUNO-COVID cohort including 538 COVID-19 patients admitted to ICU between March 2020 and May 2022. Measurements of monocyte HLA-DR expression (mHLA-DR), counts of neutrophils, of total lymphocytes, and of CD4+ and CD8+ subsets were performed five times during the first month after ICU admission. Univariate joint models combining survival at day 28 (D28), hospital discharge and longitudinal analysis of those biomarkers' kinetics with mixed-effects models were performed prior to the building of a multivariate joint model. We showed that a higher mHLA-DR value was associated with a lower risk of death. Predicted mHLA-DR nadir cutoff value that maximized the Youden index was 5414 Ab/C and led to an AUC = 0.70 confidence interval (95%CI) = [0.65; 0.75] regarding association with D28 mortality while dynamic predictions using mHLA-DR kinetics until D7, D12 and D20 showed AUCs of 0.82 [0.77; 0.87], 0.81 [0.75; 0.87] and 0.84 [0.75; 0.93]. Therefore, the final joint model provided adequate discrimination performances at D28 after collection of biomarker samples until D7, which improved as more samples were collected. After severe COVID-19, decreased mHLA-DR expression is associated with a greater risk of death at D28 independently of usual clinical confounders.

CONSORT statement adherence and risk of bias in randomized controlled trials on deep caries management: a meta-research.

BACKGROUND: Recently, trials have supported changes in deep caries management. However, reporting might lack details, affecting interpretation and implementation. Thus, we aimed to evaluate the adherence to the CONSORT statement and the risk of bias of randomized controlled trials (RCTs) on deep caries management published in pediatric dental journals. METHODS: We searched PubMed for RCTs in six pediatric dental journals between 2010 and 2022, focusing on deep caries lesion management. Adherence to the CONSORT guideline and the risk of bias were assessed using a modified tool with 19 items; each scored from 0 to 2 (maximum of 38 points), and the Cochrane risk-of-bias (RoB 2) tool. We performed descriptive and regression analyses (α = 5%). RESULTS: We analyzed 127 RCTs. The mean (standard deviation) CONSORT adherence score was 21.1 (6.7). Notably, 96.1% of the studies received a score of 2 for the "intervention" item, whereas 83.5% scored 0 for the "estimated effect size". The risk of bias assessment revealed that 40.2% of the RCTs were at high risk, 59% were at low risk, and 0.8% were at low risk. RCTs with a high risk of bias had lower CONSORT scores (p<0.001) than those with low or some concerns. RCTs published in journals without the endorsement of the CONSORT statement had lower scores than those in journals with the endorsement of the CONSORT statement. Older RCTs (6-10 years old and more than 10 years old) showed significantly lower CONSORT statement compliance than trials published recently within 5 years. CONCLUSION: Adherence to the CONSORT was relatively low among the investigated RCTs. Moreover, lower adherence to the CONSORT was associated with a higher risk of bias. TRIAL REGISTRATION: This study protocol was prospectively registered on the Open Science Framework - DOI ( 10.17605/OSF.IO/V6SYZ ).

Outcomes of chemotherapy-induced nausea and vomiting guideline adherence in pediatric and adult patients: a systematic review.

PURPOSE: This study describes chemotherapy-induced nausea and vomiting (CINV) control rates in pediatric and adult patients who did or did not receive guideline-consistent CINV prophylaxis. METHODS: We conducted a systematic literature review of studies published in 2000 or later that evaluated CINV control in patients receiving guideline-consistent vs. guideline-inconsistent CINV prophylaxis and reported at least one CINV-related patient outcome. Studies were excluded if the guideline evaluated was not publicly available or not developed by a professional organization. Over-prophylaxis was defined as antiemetic use recommended for a higher level of chemotherapy emetogenicity than a patient was receiving. RESULTS: We identified 7060 citations and retrieved 141 publications for full-text evaluation. Of these, 21 publications (14 prospective and seven retrospective studies) evaluating guidelines developed by six organizations were included. The terms used to describe CINV endpoints and definition of guideline-consistent CINV prophylaxis varied among studies. Included studies either did not address over-prophylaxis in their definition of guideline-consistent CINV prophylaxis (48%; 10/21) or defined it as guideline-inconsistent (38%; 8/21) or guideline-consistent (3/21; 14%). Eleven included studies (52%; 11/21) reported a clinically meaningful improvement in at least one CINV endpoint in patients receiving guideline-consistent CINV prophylaxis. Ten reported a statistically significant improvement. CONCLUSIONS: This evidence supports the use of guideline-consistent prophylaxis to optimize CINV control. Institutions caring for patients with cancer should systematically adapt CINV CPGs for local implementation and routinely evaluate CINV outcomes.

Intransitive Stability Collapses Under the Influence of Dominant Competitors.

AbstractIntransitive competition has received much attention over the past decade. Indeed, these cyclic arrangements of species interactions have the potential to promote and stabilize species coexistence. However, the importance of intransitive interactions in real-world species-rich communities containing a mixture of hierarchic and intransitive interactions remains unknown. Here, using simulations, we explore the behavior of intransitive loops when they interact with outer competitors, as would be expected in real-world communities. Our results show that dominant competitors often cancel the beneficial effects of intransitive loops of inferior competitors. These results call for caution when inferring beneficial effects of intransitivity on species coexistence. Although intransitive loops are a frequent motif in competition networks, their positive effects on species coexistence may be less important than previously thought. The specific properties of a subnetwork-such as stabilization by intransitive loops-should thus not be interpreted independently of the global network.

In vivo biodistribution and tumor uptake of [64Cu]-FAU nanozeolite via positron emission tomography Imaging.

Nanoparticles have emerged as promising theranostic tools for biomedical applications, notably in the treatment of cancers. However, to fully exploit their potential, a thorough understanding of their biodistribution is imperative. In this context, we prepared radioactive [64Cu]-exchanged faujasite nanosized zeolite ([64Cu]-FAU) to conduct positron emission tomography (PET) imaging tracking in preclinical glioblastoma models. In vivo results revealed a rapid and gradual accumulation over time of intravenously injected [64Cu]-FAU zeolite nanocrystals within the brain tumor, while no uptake in the healthy brain was observed. Although a specific tumor targeting was observed in the brain, the kinetics of uptake into tumor tissue was found to be dependent on the glioblastoma model. Indeed, our results showed a rapid uptake in U87-MG model while in U251-MG glioblastoma model tumor uptake was gradual over the time. Interestingly, a [64Cu] activity, decreasing over time, was also observed in organs of elimination such as kidney and liver without showing a difference in activity between both glioblastoma models. Ex vivo analyses confirmed the presence of zeolite nanocrystals in brain tumor with detection of both Si and Al elements originated from them. This radiolabelling strategy, performed for the first time using nanozeolites, enables precise tracking through PET imaging and confirms their accumulation within the glioblastoma. These findings further bolster the potential use of zeolite nanocrystals as valuable theranostic tools.

Monitoring monocyte HLA-DR expression and CD4 + T lymphocyte count in dexamethasone-treated severe COVID-19 patients.

BACKGROUND: A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented. RESULTS: To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30-6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09-4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72-13.57), p = 0.001). CONCLUSIONS: By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches.

Green synthesis of (R)-3-hydroxy-decanoic acid and analogs from levoglucosenone: a novel access to the fatty acid moiety of rhamnolipids.

Rhamnolipids (RLs) are highly valuable molecules in the cosmetic, pharmaceutic, and agricultural sectors with outstanding biosurfactant properties. In agriculture, due to their potential to artificially stimulate the natural immune system of crops (also known as elicitation), they could represent a critical substitute to conventional pesticides. However, their current synthesis methods are complex and not aligned with green chemistry principles, posing a challenge for their industrial applications. In addition, their bioproduction is cumbersome with reproducibility issues and expensive downstream processing. This work offers a more straightforward and green access to RLs, crucial to decipher their mechanisms of action and design novel potent and eco-friendly elicitors. To achieve this, we propose an efficient seven-step synthetic pathway toward (R)-3-hydroxyfatty acid chains present in RLs, starting from cellulose-derived levoglucosenone, with Michael addition, Baeyer-Villiger oxidation, Bernet-Vasella reaction, and cross-metathesis homologation as key steps. This method allowed the production of (R)-3-hydroxyfatty acid chains and derivatives with an overall yield ranging from 24% to 36%.

Lats1 and Lats2 regulate YAP and TAZ activity to control the development of mouse Sertoli cells.

Recent reports suggest that the Hippo signaling pathway regulates testis development, though its exact roles in Sertoli cell differentiation remain unknown. Here, we examined the functions of the main Hippo pathway kinases, large tumor suppressor homolog kinases 1 and 2 (Lats1 and Lats2) in developing mouse Sertoli cells. Conditional inactivation of Lats1/2 in Sertoli cells resulted in the disorganization and overgrowth of the testis cords, the induction of a testicular inflammatory response and germ cell apoptosis. Stimulated by retinoic acid 8 (STRA8) expression in germ cells additionally suggested that germ cells may have been preparing to enter meiosis prior to their loss. Gene expression analyses of the developing testes of conditional knockout animals further suggested impaired Sertoli cell differentiation, epithelial-to-mesenchymal transition, and the induction of a specific set of genes associated with Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ)-mediated integrin signaling. Finally, the involvement of YAP/TAZ in Sertoli cell differentiation was confirmed by concomitantly inactivating Yap/Taz in Lats1/2 conditional knockout model, which resulted in a partial rescue of the testicular phenotypic changes. Taken together, these results identify Hippo signaling as a crucial pathway for Sertoli cell development and provide novel insight into Sertoli cell fate maintenance.

European Organisation for Caries Research and the European Federation of Conservative Dentistry Consensus Report on Clinical Recommendations for Caries Diagnosis: Paper III - Caries Diagnosis at the Individual Level.

OBJECTIVES: The aim of the present consensus paper was to provide recommendations for clinical practice on the individual etiological and modifying factors to be assessed in the individual diagnosis of caries, and the methods for their assessment, supporting personalized treatment decisions. MATERIAL AND METHODS: The executive councils of the European Organisation for Caries Research (ORCA) and the European Federation of Conservative Dentistry (EFCD) nominated ten experts each to join the expert panel. The steering committee formed three work groups which were asked to provide recommendations on (1) caries detection and diagnostic methods, (2) caries activity assessment, and (3) forming individualized caries diagnoses. The experts responsible for "individualised caries diagnosis" searched and evaluated the relevant literature, drafted this manuscript and made provisional consensus recommendations. These recommendations were discussed and refined during the structured process in the whole work group. Finally, the agreement for each recommendation was determined using an anonymous eDelphi survey. The threshold for approval of recommendations was determined at 70% agreement. RESULTS: Ten recommendations were approved and agreed by the whole expert panel, covering medical history, caries experience, plaque, diet, fluoride, and saliva. While the level of evidence was low, the level of agreement was typically very high, except for one recommendation on salivary flow measurement, where 70% agreed. CONCLUSION: It is recommended that all aspects of caries lesion progression and activity, recent caries experience, medical conditions and medications, plaque, diet, fluoride and saliva should be synthesized to arrive at an individual diagnosis. CLINICAL RELEVANCE: The expert panel merged evidence from existing guidelines and scientific literature with practical considerations and provided recommendations for their use in daily dental practice.

Do Acoustic Characteristics of Dysarthria in People With Parkinson's Disease Differ Across Languages?

PURPOSE: Cross-language studies suggest more similarities than differences in how dysarthria affects the speech of people with Parkinson's disease (PwPD) who speak different languages. In this study, we aimed to identify the relative contribution of acoustic variables to distinguish PwPD from controls who spoke varieties of two Romance languages, French and Portuguese. METHOD: This bi-national, cross-sectional, and case-controlled study included 129 PwPD and 124 healthy controls who spoke French or Portuguese. All participants underwent the same clinical examinations, voice/speech recordings, and self-assessment questionnaires. PwPD were evaluated off and on optimal medication. Inferential analyses included Disease (controls vs. PwPD) and Language (French vs. Portuguese) as factors, and random decision forest algorithms identified relevant acoustic variables able to distinguish participants: (a) by language (French vs. Portuguese) and (b) by clinical status (PwPD on and off medication vs. controls). RESULTS: French-speaking and Portuguese-speaking individuals were distinguished from each other with over 90% accuracy by five acoustic variables (the mean fundamental frequency and the shimmer of the sustained vowel /a/ production, the oral diadochokinesis performance index, the relative sound level pressure and the relative sound pressure level standard deviation of the text reading). A distinct set of parameters discriminated between controls and PwPD: for men, maximum phonation time and the oral diadochokinesis speech proportion were the most significant variables; for women, variables calculated from the oral diadochokinesis were the most discriminative. CONCLUSIONS: Acoustic variables related to phonation and voice quality distinguished between speakers of the two languages. Variables related to pneumophonic coordination and articulation rate were the more effective in distinguishing PwPD from controls. Thus, our research findings support that respiration and diadochokinesis tasks appear to be the most appropriate to pinpoint signs of dysarthria, which are largely homogeneous and language-universal. In contrast, identifying language-specific variables with the speech tasks and acoustic variables studied was less conclusive.

Short- and long-term morbidity after Taylor flap (oblique rectus abdominis flap) for perineal reconstruction after abdominoperineal resection: A single-center series of 140 patients.

BACKGROUND: Abdominoperineal resection (APR) leads to a substantial loss of tissue and a high rate of complications. The Taylor flap is a musculocutaneous flap used in reconstruction after APR. OBJECTIVES: We aimed to analyze the short and long-term morbidity of reconstruction with a Taylor flap (oblique rectus abdominis flap) after APR and to identify the risk factors for postoperative complications. METHODS: We retrospectively included all patients who had undergone APR with immediate reconstruction with a Taylor flap in our department between July 2000 and June 2018. Demographics, oncological data, treatment, and short- and long-term morbidity were reviewed. RESULTS: Among the 140 patients included, we identified early minor complications in 42 patients (30%) and 14 early major complications (10%). Total necrosis of the flap requiring its removal occurred in four patients (2.8%). Eleven patients (7.9%) presented with a midline incision hernia, and seven (5%) presented with a subcostal incision hernia. No perineal hernia was found. No risk factors for the complications were identified. CONCLUSION: The Taylor flap is a safe procedure with few complications and limited donor site morbidity. Moreover, it prevents perineal hernias. These results confirm that the Taylor flap is a well-suited procedure for reconstruction after APR.

The biological controls of soil carbon accumulation following wildfire and harvest in boreal forests: A review.

Boreal forests are frequently subjected to disturbances, including wildfire and clear-cutting. While these disturbances can cause soil carbon (C) losses, the long-term accumulation dynamics of soil C stocks during subsequent stand development is controlled by biological processes related to the balance of net primary production (NPP) and outputs via heterotrophic respiration and leaching, many of which remain poorly understood. We review the biological processes suggested to influence soil C accumulation in boreal forests. Our review indicates that median C accumulation rates following wildfire and clear-cutting are similar (0.15 and 0.20 Mg ha-1 year-1, respectively), however, variation between studies is extremely high. Further, while many individual studies show linear increases in soil C stocks through time after disturbance, there are indications that C stock recovery is fastest early to mid-succession (e.g. 15-80 years) and then slows as forests mature (e.g. >100 years). We indicate that the rapid build-up of soil C in younger stands appears not only driven by higher plant production, but also by a high rate of mycorrhizal hyphal production, and mycorrhizal suppression of saprotrophs. As stands mature, the balance between reductions in plant and mycorrhizal production, increasing plant litter recalcitrance, and ectomycorrhizal decomposers and saprotrophs have been highlighted as key controls on soil C accumulation rates. While some of these controls appear well understood (e.g. temporal patterns in NPP, changes in aboveground litter quality), many others remain research frontiers. Notably, very little data exists describing and comparing successional patterns of root production, mycorrhizal functional traits, mycorrhizal-saprotroph interactions, or C outputs via heterotrophic respiration and dissolved organic C following different disturbances. We argue that these less frequently described controls require attention, as they will be key not only for understanding ecosystem C balances, but also for representing these dynamics more accurately in soil organic C and Earth system models.

Real-life use of letermovir prophylaxis for cytomegalovirus in heart transplant recipients.

INTRODUCTION: Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high-risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR). METHODS: In this observational, retrospective, single-center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen. RESULTS: The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor-positive, recipient-negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3-12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir. CONCLUSION: This real-life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post-treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted.

Tooth wear and bruxism: A scoping review.

OBJECTIVE: This study presents a scoping review to determine the association between tooth wear and bruxism. DATA: A protocol was developed a priori (Open Science Framework (DOI 10.17605/OSF.IO/CS7JX)). Established scoping review methods were used for screening, data extraction, and synthesis. Risk of bias was assessed using JBI tools. Direct associations between tooth wear and bruxism were assessed. SOURCES: Embase, SCOPUS, Web of Science, Cochrane, and PubMed were searched. STUDY SELECTION: Any clinical study containing tooth wear and bruxism assessment done on humans in any language was included. Animal, in-vitro studies and case reports were excluded. CONCLUSIONS: Thirty publications reporting on the association between tooth wear and bruxism were included. The majority of publications were cross-sectional studies (90%) while only three were longitudinal (10%). Eleven papers assessed definitive bruxism for analysis (instrumental tools), one paper assessed probable bruxism (clinical inspection with self-report) and eighteen assessed possible bruxism (self-report). Of the eleven papers assessing definitive bruxism, eight also reported outcomes of non-instrumental tools. Tooth wear was mostly scored using indexes. Most studies reported no or weak associations between tooth wear and bruxism, except for the studies done on cervical tooth wear. When bruxism assessment was done through self-report, more often an association was found. Studies using multivariate analyses did not find an association between tooth wear and bruxism, except the cervical wear studies. Evidence shows inconclusive results as to whether bruxism and tooth wear are related or not. Therefore, well-designed longitudinal trials are needed to address this gap in the literature. CLINICAL SIGNIFICANCE: Based on the evidence, dental clinicians should not infer bruxism activity solely on the presence of tooth wear.

Tacrolimus Monitoring in Liver Transplant Recipients, Posttransplant Cholestasis: A Comparative Between 2 Commercial Immunoassays and a Liquid Chromatography-Tandem Mass Spectrometry Method.

BACKGROUND: Cholestasis commonly occurs after orthotopic liver transplantation. It can be extrahepatic because of mechanical obstruction or intrahepatic because of various causes. During cholestasis episodes, blood concentrations of tacrolimus (TAC) metabolites may increase, potentially affecting TAC concentrations measured by immunoassays. This study aimed to simultaneously evaluate the analytical performance of 2 TAC immunoassays, a quantitative microsphere system (QMS) immunoassay, and chemiluminescence microparticle immunoassay, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a reference method in liver transplant recipients. METHODS: This single-center study included 265 patients who underwent orthotopic liver transplantation. In total, 942 blood samples were collected. TAC trough concentrations were measured using LC-MS/MS and 2 immunoassays in parallel. The plasma concentrations of conjugated bilirubin were measured in all samples. The results were analyzed using Bland-Altman plots and Passing-Bablok regressions. RESULTS: The Bland-Altman plot analysis showed that the TAC QMS immunoassay has a significant bias (+37%) compared with LC-MS/MS, and this bias was higher in patients with cholestasis with hyperbilirubinemia (≤+70% in patients with conjugated bilirubin >150 µmol/L). In comparison, the chemiluminescence microparticle immunoassay showed acceptable analytical performance in patients with hyperbilirubinemia (bias <10%). CONCLUSIONS: In agreement with previous findings, the TAC QMS immunoassay showed a positive bias compared with LC-MS/MS. This bias is remarkably high in patients with cholestasis and hyperbilirubinemia, suggesting the cross-reactivity of TAC metabolites with the monoclonal antibody used in the QMS immunoassay.

Organization for Caries Research-European Federation of Conservative Dentistry Consensus Report on Clinical Recommendations for Caries Diagnosis Paper II: Caries Lesion Activity and Progression Assessment.

INTRODUCTION: This consensus paper provides recommendations for oral health professionals on why and how to assess caries activity and progression with special respect to the site of a lesion. METHODS: An expert panel was nominated by the executive councils of the European Organization for Caries Research (ORCA) and the European Federation of Conservative Dentistry (EFCD). The steering committee built three working groups that were asked to provide recommendations on (1) caries detection and diagnostic methods, (2) caries activity and progression assessment, and (3) obtain individualized caries diagnoses. The experts of work group 2 phrased and agreed on provisional general and specific recommendations on caries lesion activity and progression, based on a review of the current literature. These recommendations were then discussed and refined in a consensus workshop followed by an anonymous Delphi survey to determine the agreement on each recommendation. RESULTS: The expert panel agreed on general (n = 7) and specific recommendations (n = 6). The specific recommendations cover coronal caries on pits and fissures, smooth surfaces, proximal surfaces, as well as root caries and secondary caries/caries adjacent to restorations and sealants. 3/13 recommendations yielded perfect agreement. CONCLUSION: The most suitable method for lesion activity assessment is the visual-tactile method. No single clinical characteristic is indicative of lesion activity; instead, lesion activity assessment is based on assessing and weighing several clinical signs. The recall intervals for visual and radiographic examination need to be adjusted to the presence of active caries lesions and recent caries progression rates. Modifications should be based on individual patient characteristics.