Corrigendum: Quantification of joint mobility limitation in adult type 1 diabetes.

[This corrects the article DOI: 10.3389/fendo.2023.1238825.].

Quantification of joint mobility limitation in adult type 1 diabetes.

Aims: Diabetic cheiroarthropathies limit hand mobility due to fibrosis and could be markers of a global profibrotic trajectory. Heterogeneity in definitions and lack of a method to measure it complicate studying associations with organ involvement and treatment outcomes. We measured metacarpophalangeal (MCP) joint extension as a metric and describe magnetic resonance (MR) imaging determinants of MCP restriction. Methods: Adults with type 1 diabetes were screened for hand manifestations using a symptom questionnaire, clinical examination, and function [Duruoz hand index (DHI) and grip strength]. Patients were segregated by mean MCP extension (<20°, 20°-40°, 40°-60°, and >60°) for MR imaging (MRI) scanning. Patients in the four groups were compared using ANOVA for clinical features and MRI tissue measurements (tenosynovial, skin, and fascia thickness). We performed multiple linear regression for determinants of MCP extension. Results: Of the 237 patients (90 men), 79 (33.8%) with cheiroarthropathy had MCP extension limitation (39° versus 61°, p < 0.01). Groups with limited MCP extension had higher DHI (1.9 vs. 0.2) but few (7%) had pain. Height, systolic blood pressure, and nephropathy were associated with mean MCP extension. Hand MRI (n = 61) showed flexor tenosynovitis in four patients and median neuritis in one patient. Groups with MCP mobility restriction had the thickest palmar skin; tendon thickness or median nerve area did not differ. Only mean palmar skin thickness was associated with MCP extension angle on multiple linear regression. Conclusion: Joint mobility limitation was quantified by restricted mean MCP extension and had structural correlates on MRI. These can serve as quantitative measures for future associative and interventional studies.

Indirect Magnetic Resonance Arthrography May Help Avoid Second Look Arthroscopy for Assessment of Healing After Bucket Handle Medial Meniscus Repairs: A Prospective Clinico-Radiological Observational Study.

OBJECTIVES: The objectives were: (1) to analyze the MRI healing rates of bucket-handle meniscus repair; (2) to compare the accuracy of assessment of meniscus healing for conventional MRI and Indirect Magnetic Resonance Arthrography (IMRA); and (3) to identify patients who may require second-look arthroscopy after meniscus repair. METHODS: This is a prospective observational case series of thirty-seven patients with repaired bucket-handle medial meniscus tear with a minimum one year follow-up. Meniscus healing rates were assessed on direct MRI and IMRA using Henning's criteria. At the same time, patients' symptoms were evaluated according to Barrett's criteria and functional outcomes were recorded using International Knee Documentation Committee (IKDC) score, Knee Osteoarthritis and Outcomes Score (KOOS) and Tegner-Lysholm scores. A further clinical review was performed 18 months after the imaging to assess the evolution of symptoms. RESULTS: At a mean of 22.3 ± 7.8 months after the meniscus repair, 56.7% patients showed complete healing and 40.5% patients demonstrated incomplete repair healing on IMRA. 52% patients with complete healing and 40% patients with incomplete healing demonstrated meniscus symptoms. At the second clinical review, 19% patients with complete healing and 20% patients with incomplete healing had meniscus symptoms. There was no co-relation between symptoms, PROMs and healing on MRI. CONCLUSION: Indirect MR arthrography offers distinct advantages over direct MRI for assessment of meniscus healing, especially in symptomatic patients. Patient-reported outcome measures and symptomatology are not co-related with the healing status of the meniscus and they resolve in the majority on longer follow-up. A more conservative approach guided by IMRA to assess meniscus healing will avoid early re-operations.

Occurrence of a Clonal T-Cell Population in a Case of Chronic Myelomonocytic Leukemia.

Chronic myelo-monocytic leukemia (CMML) is an aggressive myeloid neoplasm with some features of a myelodysplastic syndrome (MDS) and others of a myeloproliferative neoplasm (MPN). Rarely, patients with CMML have a co-existing lympho-proliferative disorder (LPD). In most cases, the lymphoid neoplasm is diagnosed first, and the CMML is considered to be a secondary therapy-induced form of leukemia. We report herein a unique case of de-novo CMML, with an underlying clonal T-cell population and describe its clinical presentation and laboratory findings. A 70-year old male presented with a 3-month history of cough, dsypnea, abdominal distension, and low-grade fever. Physical and radiological examination revealed hepatosplenomegaly but no lymphadenopathy. Peripheral blood had absolute monocytosis with marrow showing CMML with 10% blasts along with dysplasia in myeloid and erythroid lineages. Flow cytometry indicated possibility of chronic myelo-monocytic leukemia with 13% monocytic cells along with an additional clonal population of gamma/delta T cells (15%) with aberrant immunophenotype. Polymerase chain reaction (PCR) analysis was positive for clonal T-cell rearrangement. A diagnosis of CMML with an underlying clonal T-CLPD was made. The synchronous occurrence of CMML and T-cell neoplasm may be attributed to a genetic mutation common to both. Currently, there are no treatment guidelines for group of patients; hence individualized therapeutic strategies should be implemented to enable symptomatic improvement and provide optimum care.

Viscoelastic test-based bleeding risk score reliably predicts coagulopathic bleeding in decompensated cirrhosis and ACLF patients.

BACKGROUND AND AIMS: Coagulopathic bleeding risk prediction is challenging in decompensated cirrhosis (DC) by conventional assays. Viscoelastic tests (VETs) are likely to be more useful for assessing coagulation status in these patients. We investigated whether the VET (Sonoclot) parameters with fibrinogen could predict coagulopathic bleeding in these patients. PATIENTS AND METHODS: Coagulation parameters studied in 874 patients [124 compensated cirrhosis (CC), 521 DC, and 229 acute-on-chronic liver failure (ACLF)] and 190 controls. DC patients were enrolled in derivation (n = 266) and validation (n = 255) cohorts. Sonoclot variables [activated clotting time (ACT), clot rate (CR), platelet function (PF), time to peak (TP) and peak amplitude (PA)] and fibrinogen levels were measured. Coagulopathic bleeding was recorded along with 1-year survival. RESULTS: DC patients had prolonged ACT (p < 0.001), depressed CR (p = 0.059), reduced PF (p = 0.09), longer TP (p < 0.001) and smaller PA (p < 0.001), compared to CC and controls (p < 0.001 each). In derivation cohort, 32.3% patients had coagulopathic bleeding. Cox regression analysis of derivation cohort revealed; ACT > 190 s, PF < 1.25 and fibrinogen < 1.2 g/l could predict coagulopathic bleeding and were used to develop a bleeding risk score. In validation cohort; this score was comparable, correlated to real events, and had similar bleed free events with time. The score was also useful in predicting bleed in ACLF patients. In DC patients, 1-year mortality was higher those who bled and received transfusions. CONCLUSION: Viscoelasticity-based bleeding risk score using ACT, PF and fibrinogen, predicts coagulopathic bleeding in DC patients and should be useful in rationalizing transfusion of blood products. We designed a viscoelastic test-based bleeding risk score which is useful in advanced liver disease to predict the coagulation-related bleeding. This figure shows the lower bleeding-free events in advanced cirrhosis with each incremental bleeding risk score.

Inflammatory pseudotumors of the liver: Importance of a multimodal approach with the insistance of needle biopsy.

CONTEXT: Inflammatory pseudotumor (IPT) of the liver is a rare, tumor-like lesion that is considered to be biologically benign but often mimics malignancy. AIMS: The aim of the study was construe clinicopathological features, imaging findings, differential diagnosis, management, and follow-up of IPT involving the liver. SETTINGS AND DESIGN: It is a retrospective study. SUBJECTS AND METHODS: Cases included were of IPT, diagnosed on histopathology, at our center from June 2009 to December 2016. Details studied were clinical presentation, imaging studies, laboratory investigations, pathological features, treatment, and follow-up of the cases and compared with reports in the literature. RESULTS: A total of cases of IPT included were 17. The age of the patients ranged from 21 to 62 years. Common presenting features were intermittent fever, upper abdominal pain, and weight loss. Radiological diagnosis varied from neoplastic (13) to infectious etiologies (4), with hepatocellular carcinoma being the most common differential (7/17). Laboratory investigations revealed leukocytosis, hyperbilirubinemia, raised transaminases, and raised serum alkaline phosphatase. Core biopsy of a tumor conceded increased fibrosis along with mixed inflammatory cell infiltrates. Eleven cases were managed conservatively and showed regression or complete recovery. Six patients underwent surgical resection. None of these had any recurrence in median follow-up of 22 months. CONCLUSIONS: IPT of the liver can masquerade as a fatality, either primary or metastatic. It will be well managed with conservative modalities and can avoid redundant hepatectomy, reserved for complicated cases. For this intent, accurate preoperative diagnosis is the requisite, and needle biopsy with or without fine-needle aspiration cytology plays as a significant rescuer in this field.

Suboptimal Level of Bone-Forming Cells in Advanced Cirrhosis are Associated with Hepatic Osteodystrophy.

Bone loss is common in advanced cirrhosis, although the precise mechanisms underlying bone loss in cirrhosis are unknown. We studied the profile and functionality of bone-forming cells and bone-building proteins in bone marrow (BM) of individuals with cirrhosis (n = 61) and individuals without cirrhosis as normal controls (n = 50). We also performed dual energy X-ray absorptiometry for clinical correlation. BM mesenchymal cells (MSCs) were analyzed for colony-forming units-fibroblasts and their osteogenic (fibronectin-1 [FN1], insulin-like growth factor binding protein 3 [IGFBP3], collagen type 1 alpha 1 chain [COL1A1], runt-related transcription factor 2 [RUNX2], and alkaline phosphatase, liver [ALPL]) and adipogenic ( adiponectin, C1Q, and collagen domain containing [ADIPOQ], peroxisome proliferator-activated receptor gamma [PPARγ], and fatty acid binding protein 4 [FABP4]) potentials. Colony-forming units-fibroblasts were lower in patients with cirrhosis (P = 0.002) than in controls. Cirrhotic BM-MSCs showed >2-fold decrease in osteogenic markers. Compared to controls, patients with cirrhosis showed fewer osteocytes (P = 0.05), osteoblasts, chondroblasts, osteocalcin-positive (osteocalcin+) area, clusters of differentiation (CD)169+ macrophages (P < 0.001, each), and nestin+ MSCs (P = 0.001); this was more apparent in Child-Turcotte-Pugh (CTP) class C than A (P < 0.001). Multivariate logistic regression showed low nestin+ MSCs (P = 0.004) as a predictor of bone loss. Bone-resolving osteoclasts were comparable among CTP groups, but >2-fold decreased anti-osteoclastic and increased pro-osteoclastic factors were noted in patients with CTP C compared to CTP A. Bone-building proteins (osteocalcin [P = 0.008], osteonectin [P < 0.001], and bone morphogenic protein 2 [P = 0.001]) were decreased while anti-bone repair factors (fibroblast growth factor 23 [P = 0.015] and dipeptidyl peptidase 4 [P < 0.001]) were increased in BM and peripheral blood; this was more apparent in advanced cirrhosis. The dual energy X-ray absorptiometry scan T score significantly correlated with the population of osteoblasts, osteocytes, MSCs, and CD169+ macrophages. Conclusion: Osteoprogenitor cells are substantially reduced in patients with cirrhosis and more so in advanced disease. Additionally, increased anti-bone repair proteins enhance the ineffective bone repair and development of osteoporosis in cirrhosis. Hepatology Communications 2018;0:0-0).

Antimicrobial-Induced Cytopenia and Bone Marrow Hypocellularity in Patients with Cirrhosis.

There is great variation in cytopenias in cirrhotic patients with same severity and hypersplenism and their causative factors are not clear. Recent studies have highlighted the role of gut microbiome in regulation of constant and emergency hematopoiesis. Broad-spectrum antibiotics can disrupt the homeostatic or adaptive microbiota in cirrhosis, leading to impaired hematopoiesis and a higher susceptibility to infections. We studied all patients with cirrhosis with cytopenia (anemia, leucopenia, and/or thrombocytopenia), admitted in the Institute of Liver & Biliary Sciences, between January 2016 and July 2017, who underwent a bone marrow examination. The effect of the different antimicrobial agents on peripheral blood counts and bone marrow cellularity was assessed. A total of 196 patients' data was analyzed for this study. Patients on antimicrobials (n = 115) had significantly lower hemoglobin (p < 0.001), total leucocyte count (p = 0.048), and platelet count (p = 0.043) compared to patients not on antimicrobials. On unadjusted analysis, significant association with thrombocytopenia existed in beta-lactams (OR = 1.56, 95% CI = 1.06-2.40), quinolones (OR = 1.66, 95% CI = 1.11-2.61), and antifungals (OR = 2.24, 95% CI = 1.96-4.34). Cephalosporins were found to be significantly associated with anemia (OR = 1.91, 95% CI = 1.07-3.41). Patients who received antimicrobials had hypocellular marrow (p < 0.001) as compared to nonrecipients of antibiotics. The adjusted analysis showed that quinolones and beta-lactam antibiotics are the drug classes having significant association with thrombocytopenia and alternative class of drug should be explored in these patients to avoid severe thrombocytopenia.