Impact of Socioeconomic Characteristics and Comorbidities on Therapy Initiation and Outcomes of Newly Diagnosed Multiple Myeloma: Real-World Data From a Resource-Constrained Setting

BackgroundOutcomes of newly diagnosed multiple myeloma (NDMM) in developing regions have not paralleled those in developed settings. Economic disadvantage, comorbidities, and aggressive disease behavior play competing roles on defining outcomes. Our aim was to analyze the impact of socioeconomic characteristics and comorbidities on therapy initiation, drug selection, and survival outcomes of NDMM in a resource-constrained setting.Patients and MethodsThis retrospective single-center cohort included ≥ 18-year-old NDMM patients from January 2006 to December 2018.ResultsA total of 245 patients were included with a median age of 62 years, Eastern Cooperative Oncology Group performance status ≤ 2 in 70.2%, International Staging System score ≥ 2 in 89.4%, and high-risk disease in 31.6%. Comorbidities were reported in 69.4%, and Charlson comorbidity index (CCI) was ≥ 2 in 64.1%. A total of 87.4% (n = 214) received thalidomide-, alkylating-, and bortezomib-based induction in 67.8%, 18.2%, and 13.1%. Patient-related factors including performance status, comorbidities, and CCI, but not myeloma-related factors, were associated with a decreased likelihood of initiating induction therapy. On multivariate analysis, CCI ≥ 2 remained statistically significant (odds ratio, 5.81; P = .005). Overall survival was 44 months. Although both patient- and myeloma-related factors were associated with a decreased overall survival, only International Staging System score > 2 (hazard ratio, 3.53; P = .004) and induction without bortezomib-based regimens (hazard ratio, 4.45; P < .001) were statistically significant on multivariate analysis.ConclusionMyeloma- and treatment-related factors are the main determinants of survival in NDMM induction-eligible patients. Patient-related factors play a pivotal role determining access to therapy and survival outcomes. Comorbidity index and performance status were determinant on defining therapy initiation in this real-world population, which emphasizes the need to improve health baseline conditions in resource-constrained settings.     

Iron homeostasis in arthropathies: From pathogenesis to therapeutic potential

Iron is an essential element for proper functioning of cells within mammalian organ systems; in particular, iron homeostasis is critical for joint health. Excess iron can induce oxidative stress damage, associated with the pathogenesis of iron-storage and ageing-related diseases. Therefore, iron levels in body tissues and cells must be tightly regulated. In the past decades, excess iron content within joints has been found in some patients with joint diseases including hemophilic arthropathy, hemochromatosis arthropathy, and osteoarthritis (OA). Currently, increased evidence has shown that iron accumulation is closely associated with multiple pathological changes of these arthropathies. This review summarizes system-level and intracellular regulation of iron homeostasis, and emphasizes the role of iron in synovial alterations, cartilage degeneration, and subchondral bone of several arthropathies. Of note, we discuss the potential link between iron homeostasis and OA pathogenesis. Finally, we discuss the therapeutic potential of maintaining iron homeostasis in these arthropathies.     

A biocompatible supramolecular hydrogel with multivalent galactose ligands inhibiting Pseudomonas aeruginosa virulence and growth

In recent years, peptide self-assembly proved to be an efficient strategy to create complex structures or functional materials with nanoscale precision. In this work, we designed and synthesized a novel glycopeptide molecule with a galactose moiety through peptide galactosylation. Then relying on peptide self-assembling strategies, we created a supramolecular hydrogel with multivalent galactose ligands on the surface of self-assembled nanofibers for molecular recognition and interactions. Because of multivalent galactose–LecA interactions, the self-assemblies of glycopeptide could target P. aeruginosa specifically, and acted as anti-virulence and antibacterial agents to inhibit biofilm formation and bacterial growth of P. aeruginosa. Moreover, in association with polymyxin B, a common antibiotic, the glycopeptide hydrogel exhibited a synergistic growth inhibition effect on biofilm colonization of P. aeruginosa.

A glycopeptide hydrogel displaying galactoses on their surface was prepared, which inhibited Pseudomonas aeruginosa virulence and growth through multivalent interactions.     

受照脑胶质瘤细胞诱导神经干细胞旁效应

目的 探讨受照脑胶质瘤细胞U251是否可通过在未受照神经干细胞（NSCs）中产生旁效应从而影响神经干细胞的增殖、干性及分化等特性。方法 将细胞分为NSCs组、NSCs+U251组（与U251共培养的NSCs）和NSCs+受照U251组（与10 Gy X射线照射后的U251共培养的NSCs）。采用插入式小室共培养U251和NSCs。通过细胞计数、测量神经球直径等方法评估NSCs增殖、成球能力的变化;采用免疫荧光实验检测Nestin蛋白的表达评估NSCs干性维持能力的变化;检测Tuj1、GFAP蛋白的表达、测量分化后神经元细胞的树突数目、轴突长度以及胶质细胞突起终端数、突起长度等评估神经干细胞分化能力的变化情况。结果 NSCs+受照U251组的细胞数量明显低于NSCs+U251组（t=2.52,P<0.05）;NSCs+受照U251组的Nestin阳性率和成球能力明显低于NSCs+U251组（t=-3.50,P<0.05）;NSCs+受照U251组向神经元和胶质细胞（t=6.09,P<0.05）分化的比例和程度也明显低于NSCs+U251组。结论 受照胶质瘤细胞可通过电离辐射旁效应显著抑制未受照神经干细胞的增殖、干性和分化能力。     

Parathyroid conditions in childhood

This review of parathyroid surgery in children will briefly discuss parathyroid gland embryology and anatomy before focusing on the pathophysiology, clinical presentation, and treatment of hyperparathyroidism in children. Hyperparathyroidism (HPT) is the overproduction of PTH and it is rare in children, with an incidence of 2-5 per 100,000. This rarity means that the principles of caring for children with parathyroid disease are largely extrapolated from the richer adult experience; however, the unique pediatric aspects of parathyroid problems and their surgical treatment, including presentation, imaging, operative approach, and complications, will be considered.