Recurrence of progressive multifocal leukoencephalopathy despite immune recovery in two HIV seropositive individuals

We present two cases of recurrent progressive multifocal leukoencephalopathy (PML) in patients with long standing virally suppressed human immunodeficiency virus (HIV) and normal CD4+ T cell count who were taking stable regimens of highly active antiretroviral therapy (HAART). This has significant implications for other patients with a past history of PML, not just those with HIV but also those on medications such as natalizumab or fumarates.     

A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

Presenting features and prognosis of chronic lymphocytic leukemia in younger adults

We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.     

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma

Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.     

Prevalence and Risk Factors of Spine,Shoulder, Hand,Hip, and Knee Osteoarthritis in Community-dwelling Koreans Older Than Age 65 Years

Background

Osteoarthritis (OA) is common and disabling among older patients around the world. Data exploring the prevalence and risk factors of OA are of paramount importance in establishing healthcare policies. However, few studies have evaluated these topics among Asian populations.

Questions/purposes

This study was conducted to determine the prevalence and risk factors of radiographic OA in the spine, shoulder, hand, hip, and knee in Koreans older than age 65 years.

Methods

A simple random sample (N = 1118) was drawn from a roster of elderly individuals older than age 65 years in Seongnam. Of the 1118 invited subjects, 696 (males = 298, females = 398) participated in this study (a response rate of 62%). The mean age of respondents was 72 ± 5 years (range, 65–91 years). Radiographs of the lumbar spine, shoulder, hand, hip, and knee were taken and afterward evaluated for radiographic OA. The Kellgren-Lawrence grading system was used for all mentioned joints, and radiographic OA was defined as Grade 2 changes or higher. The association of sex, aging, and obesity with OA in each of the mentioned joints was determined with the help of multivariate logistic regression.

Results

The highest prevalence of radiographic OA was seen in the spine (number of subjects with OA/number of whole population = 462 of 696 [66%]) followed by the hand (415 of 692 [60%]), knee (265 of 696 [38%]), shoulder (36 of 696 [5%]), and hip (15 of 686 [2%]). Female sex was associated with knee OA (odds ratio [OR], 5.7; 95% confidence interval [CI], 3.9–8.4; p < 0.001) and hand OA (OR, 2.3; 95% CI, 1.6–3.1; p < 0.001), and male sex was associated with spine OA (OR, 0.7; 95% CI, 0.5–1.0; p = 0.025). Aging was associated with radiographic OA in the spine, knee, and hand (OR per 5-year increments, 1.3 [95% CI, 1.1–1.6; p = 0.001], 1.6 [95% CI, 1.4–1.9; p < 0.001], and 1.4 [95% CI, 1.2–1.7; p < 0.001]), respectively) but not associated with OA in the hip and shoulder. Obesity was associated with knee OA (OR, 3.4; 95% CI, 2.4–5.0; p < 0.001) and spine OA (OR, 1.5; 95% CI, 1.1–2.2; p = 0.014) but not with OA in other joints.

Conclusions

OA of the spine, hand, and knee is likely to become a major public health problem rather than shoulder and hip OA in Korea. Associations of demographic factors with radiographic OA differed among each joint, and that would be valuable information to assess the role and influence of risk factors of OA in various joints.

Level of Evidence

Level III, prognostic study.