An alternative dosing strategy for ropeginterferon alfa-2b may help improve outcomes in myeloproliferative neoplasms: An overview of previous and ongoing studies with perspectives on the future

Ropeginterferon alfa-2b is a novel, long-acting mono-pegylated proline-IFN-alpha-2b approved for treatment of polycythemia vera in adults, regardless of thrombotic risk level or treatment history. Clinical trial data indicate the dose and titration of ropeginterferon alfa-2b is safe and effective. However, additional studies may provide rationale for an amended, higher initial dosage and rapid titration. This article is an overview of current and upcoming studies of ropeginterferon alfa-2b in myeloproliferative neoplasms that support the exploration of an amended dosing scheme in order to optimize patient tolerability and efficacy outcomes

Metastatic primary neuroendocrine carcinoma of the breast (NECB)

Neuroendocrine carcinoma of the breast (NECB) is a subtype of breast cancer. The diagnostic criteria of primary NECB were established in 2003 and updated in 2012. It is a rare entity, and few studies have reported the histogenesis, immunohistochemistry for a pathological diagnosis, clinical behavior, therapeutic strategies, and the prognostic factors. Because of the rarity of this disease, consistent diagnostic criteria will remind physicians of this disease when making a differential diagnosis to enable a timely diagnosis and prompt treatment. Herein, we report a case of primary NECB who presented with a history of right hip pain arising from an osteolytic lesion in the right acetabulum and ischium. The course of investigation started with metastasis in the right hip and concluded with a diagnosis of NECB. In addition to the case report, we also conducted a literature review

Post-weaning high-fat diet results in growth cartilage lesions in young male rats.

To determine if a high-fat diet (HF) from weaning would result in a pro-inflammatory state and affect joint cartilage, we fed male rats either HF or Chow diet post-weaning, and voluntary wheel exercise (EX) or cage only activity (SED) after 9 weeks of age. At 17 weeks body composition, plasma biomarkers and histomorphology scores of femoro-tibial cartilages of HF-SED, HF-EX, Chow-SED and Chow-EX groups were compared. Food intake and activity were not significantly different between groups. HF diet resulted in significantly higher weight gain, %fat, fat:lean ratio, and plasma leptin, insulin and TNFα concentrations, with significant interactions between diet and exercise. No abnormal features were detected in the hyaline articular cartilage or in the metaphyseal growth plate in all four groups. However, collagen type X- positive regions of retained epiphyseal growth cartilage (EGC) was present in all HF-fed animals and significantly greater than that observed in Chow-fed sedentary rats. Most lesions were located in the lateral posterior aspect of the tibia and/or femur. The severity of lesions was greater in HF-fed animals. Although exercise had a significantly greater effect in reducing adiposity and associated systemic inflammation in HF-fed rats, it had no effect on lesion incidence or severity. Lesion incidence was also significantly associated with indices of obesity and plasma markers of chronic inflammation. Clinically, EGC lesions induced by HF feeding in rats from very early in life, and possibly by insufficient activity, is typical of osteochondrosis in animals. Such lesions may be the precursor of juvenile osteochondritis dissecans requiring surgery in children/adolescents, conservative management of which could benefit from improved understanding of early changes in cellular and gene expression

Post-weaning high-fat diet results in growth cartilage lesions in young male rats - Fig 3

<p>(A) Representative sections of Grade 0 and Grade 1 lesions from all 4 groups. (B) Grade 2 lesions were detected in high fat-fed rats only (total of 4 lesions detected) * indicates regions of fibrosis at the interface of the subchondral bone and EPG lesion; arrows indicate fissures within the lesion. (C) Incidence (%) of rats in which one or more lesions were detected. (D) Mean (±SEM) severity score (sum of grades from all 6 sites examined in each joint). n = 8 for SED groups, n = 10 for EX groups. * p < 0.05, **p < 0.01, ***p < 0.001. * indicates comparisons between chow and HF diets and + indicates comparisons between exercised groups.</p

Post-weaning high-fat diet results in growth cartilage lesions in young male rats - Fig 5

<p>(A) Collagen type X labelling (brown) in the hyaline articular cartilage region in a section graded 0. Staining is specifically localised in hypertrophic cells below the tidemark. (B) Collagen type X distribution in the metaphyseal growth plate. (C) Negative control (no primary antibody) section of a Grade 1 lesion. (D) Collagen type X distribution within the retained epiphyseal growth cartilage.</p

Mean (± SEM) body weight (g), body fat (%), lean mass (g), leptin (ng/ ml), insulin (ng/ml) and plasma cytokines (pg/ ml) in groups of animals with or without a lesion.

<p>Statistical significance of the association was assessed by Mann-Whitney U test. No lesion (n = 18) and lesion (n = 22) groups and * p < 0.05 was considered statistically significant.</p

Diet and exercise changes in body parameters on d117 rats.

<p>(A) body mass (g), (B) gain (g) from d63-d121, (C) total body fat (%) (D) lean mass (g) (E) fat:lean ratio, and (F) femur length (mm). Data represents the mean (±SEM) from n = 10 rats/ group. Exercise data: (G) distance travelled (m) on d70, 80, 90, 100 and 110 in Chow and HF pairs and, (F) total distance travelled over the exercise intervention period. Exercise data (G, H) represents data obtained from running wheel per cage (2 animals/ per cage).</p

Epiphyseal growth cartilage grading system.

<p>Epiphyseal growth cartilage grading system.</p

Representative toluidine-stained sagittal knee sections illustrating distal femoral epiphyseal cartilage graded 0, 1, 2 using a modified scoring detailed in Table 1.

<p>Grade 0 shows hyaline articular cartilage (HAC) and tidemark (black arrow). Grades 1and 2 show retained epiphyseal growth cartilage (EGC) containing hypertrophic cells with toluidine blue stained lacunae (arrowheads; Grade 1), and in grade 2 fibrosis, stained blue, is present between the retained EPG and the subchondral bone (black arrow) and a cavity/ cyst within the fibrotic tissue (*). Grade 3 lesions were not detected in this study.</p

Representative toluidine stained sagittal sections of d117 metaphyseal growth plates from all four groups.

<p>No lesions or areas of retained growth cartilage were detected in any group. * indicates regions of acellularity, a common characteristic of physes of rats older than 16 weeks.</p