Objective To characterize the risk factors, clinical course, and treatment of patients with progressive multifocal leukoencephalopathy (PML) diagnosed and followed over a 25-year epoch at 2 academic hospitals. Methods Patients with a definite diagnosis of PML were identified by positive CSF PCR for JC virus or histopathology between January 1, 1994, and January 1, 2019. Demographic and PML-specific variables were recorded on symptomatic presentation and at follow-up, including risk factors, clinical outcome, neuroimaging findings, and modified Rankin Scale (mRS) score at last follow-up. Results There were 91 patients with confirmed PML. HIV infection was the most common risk factor, identified in 49% (n = 45). Other frequent risk factors included lymphoma, leukemia, or myelodysplasia, identified in 31% of patients (n = 28); exposure to chemotherapeutic medications (30%, n = 27); and exposure to monoclonal antibody therapies (19%, n = 17). Thirty percent of the cohort was alive at the time of censoring, with a median mRS of 2 points, indicating slight disability at last follow-up. Median survival following PML diagnosis in HIV-infected patients was longer than in HIV-uninfected patients (1,992 vs 101 days, p = 0.024). Forty patients survived more than 1 year after PML symptom onset, of whom 24 were HIV infected (60%). Thirteen patients survived more than 10 years after PML symptom onset, all HIV infected, of the 59 patients diagnosed before June 1, 2009, and eligible for 10-year survivor status (22%). Conclusions We add to the limited literature on PML by reporting its epidemiology in a large observational cohort. These parameters may be useful for future clinical trials that measure survival and clinical outcomes.

https://nn.neurology.org/content/nnn/6/6/e618.full.pdf

Progressive multifocal leukoencephalopathy: A 25-year retrospective cohort study.

Cellulosic fines: Properties and effects

OBJECTIVE: To determine the burden of comorbidities in OA and their temporal relationships in the UK. METHODS: The Clinical Practice Research Datalink (CPRD) GOLD was used to identify people with incident OA and age, gender and practice matched non-OA controls from UK primary care. Controls were assigned the same index date as matched cases (date of OA diagnosis). Associations between OA and 49 individual comorbidities and multimorbidities (two or more comorbidities excluding OA) both before and after OA diagnosis were estimated, adjusting for covariates, using odds ratios (aORs) and hazard ratios (aHRs), respectively. RESULTS: During 1997-2017, we identified 221 807 incident OA cases and 221 807 matched controls. Of 49 comorbidities examined, 38 were associated with OA both prior to and following the diagnosis of OA and 2 (dementia and systemic lupus erythematosus) were associated with OA only following the diagnosis of OA. People with OA had a higher risk of developing heart failure [aHR 1.63 (95% CI 1.56, 1.71)], dementia [aHR 1.62 (95% CI 1.56, 1.68)], liver diseases [aHR 1.51 (95% CI 1.37, 1.67)], irritable bowel syndrome [aHR 1.51 (95% CI 1.45, 1.58)], gastrointestinal bleeding [aHR 1.49 (95% CI 1.39, 1.59)], 10 musculoskeletal conditions and 25 other conditions following OA diagnosis. The aOR for multimorbidity prior to the index date was 1.71 (95% CI 1.69, 1.74), whereas the aHR for multimorbidity after the index date was 1.29 (95% CI 1.28, 1.30). CONCLUSIONS: People with OA are more likely to have other chronic conditions both before and after the OA diagnosis. Further study on shared aetiology and causality of these associations is needed.

/pdf/temporal-relationship-between-osteoarthritis-and-315op8ypdz.pdf

Temporal relationship between osteoarthritis and comorbidities: a combined case control and cohort study in the UK primary care setting.

Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders.

Nutrition in Chronic Liver Disease: Consensus Statement of the Indian National Association for Study of the Liver.

Almost all patients with chronic liver diseases (CLD) show altered bone metabolism. Depending on the etiology, this manifests in a severe osteoporosis in up to 75% of the affected patients. Due to high prevalence, the generic term hepatic osteodystrophy (HOD) evolved, describing altered bone metabolism, decreased bone mineral density, and deterioration of bone structure in patients with CLD. Once developed, HOD is difficult to treat and increases the risk of fragility fractures. Existing fractures affect the quality of life and, more importantly, long-term prognosis of these patients, which presents with increased mortality. Thus, special care is required to support the healing process. However, for early diagnosis (reduce fracture risk) and development of adequate treatment strategies (support healing of existing fractures), it is essential to understand the underlying mechanisms that link disturbed liver function with this bone phenotype. In the present review, we summarize proposed molecular mechanisms favoring the development of HOD and compromising the healing of associated fractures, including alterations in vitamin D metabolism and action, disbalances in transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signaling with histone deacetylases (HDACs) as secondary regulators, as well as alterations in the receptor activator of nuclear factor kappa B ligand (RANKL)–osteoprotegerin (OPG) system mediated by sclerostin. Based on these mechanisms, we give an overview on the limitations of early diagnosis of HOD with established serum markers.

https://www.mdpi.com/1422-0067/20/10/2555/pdf

Hepatic Osteodystrophy-Molecular Mechanisms Proposed to Favor Its Development.

Purpose: Paraduodenal pancreatitis (PP) is a unique form of focal chronic pancreatitis that selectively involves the duodenum and aberrant pancreatic tissue located near the minor papilla (beyond the pancreas proper). The pseudotumoral nature of the disease often generates considerable clinical quandary and patient apprehension, and therefore merits a better understanding. The present study appraises the clinicoradiological manifestations of PP in 33 patients. Materials and Methods: Clinical, laboratory, and radiological manifestations of 33 patients of PP treated in gastroenterology/hepatology and hepato-pancreatico-biliary surgery units during June 2010-August 2014 were retrospectively reviewed. Results: All patients were young to middle-aged men (100%) with history of alcohol abuse (93.9%) and/or smoking (42.4%), who presented either with acute or gradually worsening abdominal pain (90.9%). Pancreatic enzymes and serum tumor markers remained normal or were mildly/transiently elevated. Cystic variant was detected in 57.6% (solid in 42.4%); the disease remained confined to the groove/duodenum (pure form) in 45.4%. Medial duodenal wall thickening with increased enhancement was seen in 87.87 and 81.81%, respectively, and duodenal/paraduodenal cysts were seen in 78.78%. Pancreatic calcifications and biliary stricture were seen 27.3% patients. Peripancreatic arteries were neither infiltrated nor encased. Conclusion: PP has a discrete predilection for middle-aged men with history of longstanding alcohol abuse and/or smoking. Distinguishing imaging findings include thickening of the pancreatic side of duodenum exhibiting increased enhancement with intramural/paraduodenal cysts. This may be accompanied by plate-like scar tissue in the groove region, which may simulate groove pancreatic carcinoma. However, as opposed to carcinoma, the peripancreatic arteries are neither infiltrated nor encased, rather are medially displaced.

Clinicoradiological appraisal of 'paraduodenal pancreatitis': Pancreatitis outside the pancreas!

Purpose: To study the imaging findings in gangrenous acute cholecystitis. Materials and Methods: Retrospective analysis of imaging findings in 31 histopathologically confirmed cases of gangrenous cholecystitis was done. The following imaging findings were analyzed: wall thickness, gallbladder distension, intraluminal membranes, mural striation, edema, wall enhancement, gallstones, gas, pericholecystic fluid, stranding, hemorrhage, hyperaemia in adjacent liver, mucosal/wall irregularity, complications. Statistical Analysis: Appropriate statistical tests were used using SPSS.22.0 software. The two proportions were compared using Chi-square or Fisher exact test and two means were compared using student t test. Results: Mean gallbladder wall thickening was 6 ± 1.93 mm. Gallstones, mural edema, mural striation, pericholecystic fluid, intraluminal membranes, gas were seen in 30, 27, 18, 20, 14 and 3 cases respectively. The mean short-axis distension of gallbladder lumen was 4.24 ± 0.91 cm. Gallbladder wall enhancement was studied in only 10 cases. Complete absence of enhancement was seen in 1, focal decreased enhancement in 8 cases. Mucosal/wall irregularity was seen in 28 cases. 74.2% cases had ≥4 cm gallbladder distension. Intraluminal membranes were present in 14 cases with mean short-axis distension of 4.6 cm and absent in 17 (P = 0.041), in 11 cases with mural striation (P = 0.036). Mean wall thickening was 6.69mm in patients with intraluminal membranes and 5.46 mm with absence of membranes (P = .078). Conclusion: Presence of more than one of these findings - gallbladder distension (short axis diameter of ≥4 cm), intraluminal membranes, mural striation, absent or decreased enhancement of gallbladder wall suggest high probability of gangrenous change in acute cholecystitis.

/pdf/gangrenous-cholecystitis-analysis-of-imaging-findings-in-47hbl24ttq.pdf

Gangrenous cholecystitis: Analysis of imaging findings in histopathologically confirmed cases

Beating or refining is an energy intensive process in paper industry. In India, most of the paper industries blend long fibered softwood pulps with short fibered hardwood or agro based pulps to get the paper properties of competitive level. Refining characteristics of the blend of pulps is very crucial with respect to freeness and strength properties. This study has been carried out to understand the refining behavior of three hardwood pulps and a softwood pulp. The hardwood and softwood pulps are blended in different proportions in two different ways; a) blending after their separate refining, and b) blending before refining followed by mixed refining of the blended pulps. Freeness of pulp, strength, optical and surface properties of paper along with formation have been determined and compared for both the refining methods. The fiber classification of refined pulps was also carried out to analyze the effect of refining method on fiber morphology. The mixed refining of hardwood and softwood pulps marginally affects the fiber morphology in comparison to separate refining of pulps. The strength and other properties of paper prepared from mixed refining of pulps are either better or comparable than those of separately refined pulps.

Effect of separate and mixed refining of hardwood and softwood pulps on paper properties

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 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).

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

Musculoskeletal problems in patients with liver disease are common; however, they are not so well described in the literature. Therefore, there is a need to collate information on these disorders, as their incidence is on a constant rise and some of these pathologies can severely debilitate the patient's quality of life. These disorders are parietal wall varices with or without bleeding, spontaneous intramuscular haematoma (e.g. rectus sheath), abdominal wall hernia, anasarca, hepatic osteodystrophy, septic arthritis, osteomyelitis, necrotizing fasciitis, osseous metastases from hepatocellular carcinoma etc. While portal hypertension plays a key role in disorders, in others, dysregulation of the coagulation system or a compromised immune system are responsible. Imaging plays an essential role in the assessment of these complications and awareness of these musculoskeletal manifestations is vital for establishing a timely diagnosis and planning of appropriate therapy, as these disorders can significantly impact the morbidity and mortality and also influence candidacy for liver transplantation. We herein comprehensively appraise various musculoskeletal complications associated with chronic liver disease/liver cirrhosis especially from an imaging perspective which, to the best of our knowledge, have not been collectively described in English literature.

Shalini Thapar

Papers

Clinicoradiological appraisal of 'paraduodenal pancreatitis': Pancreatitis outside the pancreas!

Gangrenous cholecystitis: Analysis of imaging findings in histopathologically confirmed cases

Effect of separate and mixed refining of hardwood and softwood pulps on paper properties

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

Cirrhosis-related musculoskeletal disease: radiological review.