Systemic lupus erythematosus and damage: What has changed over the past 20 years?

The young age of onset and chronic/relapsing nature of systemic lupus erythematosus (SLE) make SLE patients prone to develop and accrue organ damage as a result of long-standing disease activity and side effects of treatment. There is a growing interest in objectifying damage and identifying its risk factors. Still, the lack of therapeutic alternatives has led to difficulties in avoiding immunosuppressives particularly corticosteroids, which have been implicated in a large spectrum of organ damage in SLE patients. Moreover, it continues to be very challenging to determine what actually causes damage in different organ-systems. Cardiovascular disease continues to be one of the leading types of damage in patients with SLE, reported as early as 1976. Since then, many researchers have focused on identifying SLE or treatment-related and traditional risk factors. The same considerations are valid for other conditions, such as the occurrence of metabolic syndrome, osteoporosis, avascular necrosis, susceptibility to infections, etc. On the other hand, diverse risk factors contribute to the development of chronic kidney disease (CKD) in SLE. Most evidence suggests that high initial levels of serum creatinine, hypocomplementemia, nephrotic range proteinuria, concomitant uncontrolled hypertension, Black and Hispanic ancestry, non-adherence to treatment, and biopsy findings such as diffuse proliferative lupus nephritis (LN), a high chronicity index, tubular atrophy, and tubulointerstitial inflammation are risk factors for progression to end stage renal disease (ESRD) in LN. While cardiovascular disease, CKD and infections are leading causes of mortality in patients with SLE, hospitalizations are caused mostly by SLE disease flares and infections. Cognitive impairment and mood disorders are common in SLE but continue to impose a challenge on how to measure, manage and decipher the underlying pathogenesis. Nevertheless, they have a great impact on SLE patients' health-related quality of life (HRQoL) and social functioning. Also, skin manifestations, such as alopecia and scaring, cataracts, and sicca symptoms result in a significant decrease in HRQoL. In light of recent developments in SLE treatment, we can expect to enter a period of new-age targeted therapies that will enable us to reduce disease activity and glucocorticoid usage further and positively alter the trajectory of damage development and accrual in SLE.

Omentin-1 Levels in Hypothyroid Patients with Autoimmune Thyroiditis.

OBJECTIVE: To determine Omentin-1 in hypothyroid patients with autoimmune thyroiditis compared to controls. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Internal Medicine and Endocrinology, University of Health Sciences, Antalya Training and Research Hospital, Turkiye, between August 2017 and March 2020. METHODOLOGY: The study included 63 newly diagnosed hypothyroid patients with autoimmune thyroiditis and 40 healthy volunteers. Body mass index, fasting blood glucose, homeostasis model assessment for insulin resistance, lipid profile, thyroid function tests, thyroid autoantibodies, and omentin-1 levels were determined before and after treatment with levothyroxine sodium in all participants. RESULTS: Omentin-1 was significantly higher in the control subjects [15.05 (12.12-18.06) ng/ml] than in the hypothyroid patients with autoimmune thyroiditis [3.04 (2.39-3.76) ng/ml, p<0.001]. There was no significant difference in omentin-1 level in patients who achieved euthyroidism by treatment (p=0.26). In correlation analysis, serum omentin-1 level was found to correlate negatively with thyroid-stimulating hormone (r=-0.27, p=0.006), anti-thyroid peroxidase (r=-0.32, p=0.001), and anti-thyroglobulin antibodies (r=-0.26, p=0.007), whereas it correlated positively with free triiodothyronine (r=0.22, p=0.021) and free thyroxine (r=0.24, p=0.012). CONCLUSION: Lower omentin-1 levels in hypothyroid patients with autoimmune thyroiditis and its negative correlation with thyroid-stimulating hormone suggest that omentin-1 may play some role in hypothyroidism and autoimmune thyroiditis. KEY WORDS: Hypothyroidism, Chronic autoimmune thyroiditis, Omentin-1.

GMFCS level improvement in children with cerebral palsy treated with repeat botulinum toxin injections and intensive rehabilitation: A retrospective study.

PURPOSE: The Gross Motor Functional Classification System (GMFCS) provides a standardized classification of motor disability in children with cerebral palsy (CP) that is typically considered longitudinally stable. Here, changes in GMFCS levels of children with CP who received repeated botulinum toxin A (BoNT-A) injections within an intensive rehabilitation approach were evaluated. METHODS: This retrospective, observational study included 503 children with CP (GMFCS I-V) treated in a single university rehabilitation clinic. Individualized treatment plans and a variety of rehabilitation techniques were incorporated within an integrated model of care. Each child received≥2 repeated BoNT-A injections as well as an intensive rehabilitation program. RESULTS: GMFCS level following repeat treatment improved in 42.1% of the patients and worsened in 3 patients; 14.9% of children showed improvement after 1 treatment cycle, 12.3% after 2 cycles, 7.6% after 3 cycles, 3.6% after 4 cycles, and 3.8% after≥5 cycles. Type of involvement (p < 0.001), baseline GMFCS (p = 0.001), number of treatment cycles (p < 0.001) and presence of severe dystonia (p = 0.032) were significant predictors of GMFCS improvement, but age and gender were not. CONCLUSION: Children with CP may change GMFCS level when intensive rehabilitation programs are combined with repeated BoNT-A injections.

Preparation and characterization of novel albumin-sericin nanoparticles as siRNA delivery vehicle for laryngeal cancer treatment.

Small interfering RNA (siRNA)-based gene silencing strategy has high potential on suppressing specific molecular targets, involved in cancer progression. However, the lack of an effective nanocarrier system that safely delivers siRNA to its target still limits the clinical applications of siRNA. This study aimed to develop albumin-sericin nanoparticles (Alb-Ser NPs) as a novel siRNA delivery system for laryngeal cancer treatment. Nanoparticle formulations composed of albumin and sericin at different ratios (1:1, 2:1, 1:2 w/w) were synthesized by desolvation method. The nanoparticles were modified with poly-L-lysine (PLL) for siRNA binding and decorated with hyaluronic acid (HA) to target laryngeal cancer cell line, Hep-2. HA/PLL/Alb-Ser NPs were individually loaded with siRNAs for casein kinase 2 (CK2), Absent, Small, or Homeotic-Like (ASH2L), and Cyclin D1 genes, which are overexpressed in Hep-2 cells. Downregulation of genes was confirmed by real-time PCR (RT-PCR). Size, morphological, and thermogravimetric characterizations revealed that Alb-Ser NPs having 2:1 (w/w) ratio are the most optimized formulation. Between 36.8 and 61.3% of siRNA entrapment efficiencies were achieved. HA/PLL-siRNA/Alb-Ser (2:1) NPs-mediated gene silencing resulted in a significant inhibition of cell growth and induction of apoptosis in cells. Our findings showed that HA/PLL/Alb-Ser (2:1) NPs were promising as a siRNA carrier.