Analysis of vitamin D availability of premature infants in the south of Russia

Introduction. Inadequate vitamin D supply worldwide is a public health problem. Low vitamin D levels during pregnancy can lead to abnormal placentation, placental insufficiency and abnormal fetal development, which contributes to poor health after birth.Objective of the study is to analyze the vitamin D status of premature infants born in the south of Russia.Materials and methods. A total of 141 premature infants were examined. Extremely low birth weight was found in 19 (13.4%) newborns, very low birth weight in 35 (24.8%), and low birth weight in 75 (53.2%).Results and discussion. Premature infants had vitamin D deficiency in the majority of cases (51%), with a median of 16.9 [11.7; 22.9] ng/mL. Correlation analysis demonstrated a positive association between 25(OH)D levels and body weight in very low birth weight infants (r = 0.34, p = 0.043). Serum vitamin D concentrations were 1.6 times lower in infants whose mothers did not receive multivitamins than in those whose mothers received multivitamins, 13.8 [9.7; 20.9] and 21.6 [16.9; 28.6] ng/mL, respectively (p = 0.001). Infants with an Apgar score of 7-10 had higher vitamin D levels, 17.8 [11.9; 22.7] ng/mL, than infants with severe asphyxia, 13.8 [9.9; 16.8] ng/mL (p = 0.036). Premature infants with congenital infection had lower 25(OH)D levels than infants without an infectious process, 15.6 [10.8; 22.9] and 18.4 [14.2; 22.7] ng/mL, respectively. Children with an infectious process that subsequently ended in death had lower 25(OH)D levels than children without an infectious process (p = 0.001). Children with cerebral ischemia had lower 25(OH)D concentrations than children without cerebral ischemia (p = 0.001).Conclusions. Premature infants born in the south of Russia have vitamin D deficiency in more than half of the cases. Administration of preparations containing cholecalciferol reduces the proportion of newborns with severe vitamin D deficiency, but does not ensure optimal serum levels. Initially low levels of 25(OH)D can be considered as an unfavorable prognostic sign against the background of the development of congenital infection

EXPERIENCE WITH EFFECTIVE COMBINED ANTI-B-CELL THERAPY WITH RITUXIMAB AND BELIMUMAB FOR REFRACTORY GRANULOMATOSIS WITH POLYANGIITIS (WEGENER'S) WITH SEVERE LUNG DAMAGE

Systemic vasculitis (SV) associated with antineutrophil cytoplasmic antibodies (ANCA) is characterized by severe multiple organ lesions with a poor prognosis. The successful introduction of standard therapy with cyclophosphamide (CP) and innovative anti-B-cell therapy with rituximab (RTM) for the treatment of ANCA SV gives no grounds to stop further searching for effective and safe therapy since about 10–15% of patients with ANCA SV are refractory to standard therapy with CP; after the latter, approximately 40% of patients develop recurrences, and granulomatous inflammation in the respiratory organs in granulomatosis with polyangiitis (GPA) can be resistant to RTM treatment, especially following its single cycle. There is increasing evidence that the efficiency of anti-B-cell therapy can be enhanced by adding belimumab (BLM). The paper describes a clinical case of effective sequential combined anti-B-cell therapy with BLM and RTM for remission induction in a female patient who has GPA with severe granulomatous lung injury refractory to previous therapy with CP (a total dose of 6.2 g) and a single cycle of therapy with RTM (a total dose of 2.6 g). BLM was used 12 months after RTM administration because there were no positive changes in lung injury. At 12 months after initiations of treatment with BLM (800 mg twice at a weekly interval, then 800 mg monthly), there was a substantial reduction in the lung parenchymal foci, as evidenced by multislice spiral computed tomography (MSCT); and the treatment was continued for another 6 months, thereafter discontinued due to the occurrence of ulcerative stomatitis. After its relief, RTM was again given at reduced dose cycles of 500 mg every 6 months; lung MSCT showed further improvement and remission achieved. BLM may be effective in treating the GPA patients who are refractory to CP and have an insufficient response to RMT treatment. Combined anti-B-cell therapy aimed at depleting SD20+ B-cells and at blocking BAFF may be a promising area for the treatment of patients with ANCA SV

PROBLEMS IN THE DIAGNOSIS AND TREATMENT OF ANCA-ASSOCIATED SYSTEMIC VASCULITIS: IN THE FOCUS OF ANCA-NEGATIVE PAUCI-IMMUNE GLOMERULONEPHRITIS

One of the most common  causes of rapidly progressive glomerulonephritis (GN)  is the so-called pauci-immune crescentic GN that is characterized  by no luminescence  in kidney tissue samples during immunofluorescence microscopy and by the hyperproduction of antineutrophil cytoplasmic antibodies (ANCA). At the same time, serum ANCAs are absent in a number of cases of pauci-immune GN. Based on their own experience, the authors present the clinical and morphological characteristics of patients with ANCA-negative  pauci-immune GN and analyze the data available in the literature.Subjects and methods. This retrospective study included 8 patients with ANCA-negative  pauci-immune GN,  who were followed up at two Russian centers (the Center of Nephrology and the Center of Rheumatology) in 2011 to 2015. Results and discussion. According to our data, ANCAs are not detectable in 6% of the patients with ANCA-associated systemic vasculitis (SV) with renal involvement and/or pauci-immune GN.  The mean age at onset of the disease in the ANCA-negative  patients was 50±18 years (range 19 to 74 years); the male/female  ratio was 1:1. Four (50%) cases were diagnosed with microscopic polyangiitis; 2 cases had granulomatosis with polyangiitis; isolated renal injury was present in other 2 patients. The Birmingham SV activity index averaged 19.6±7.9.  Hematuria  was observed in all cases and it was massive in 4. The mean daily urinary protein level was 3.4±2.7 g; three (38%) patients were observed to have nephrotic  syndrome. The blood creatinine  level averaged 704±405 μmol/l;  GN was characterized  by a rapidly progressive course in 6 (75%) patients; hemodialysis was needed in 5. A morphological study of the kidney determined  crescents (in on an average of 52 glomeruli) in the majority of cases and glomerulosclerosis in one patient. All the patients were observed to have varying degrees of interstitial fibrosis. Three (38%) treated patients achieved remission. The mortality rates were 38%. Interestingly,  the data from our group as well those obtained by the study of European  cohorts were slightly different from those of the studies conducted  in Asia, according to which a renal biopsy more frequently revealed glomerular crescents; the levels of protein in the urine were higher and renal survival was worse.Thus, serum ANCAs are absent in 3–39% of cases of pauci-immune crescentic GN,  but the clinical and morphological picture corresponds to ANCA-associated  SV. A kidney biopsy helps establish the correct diagnosis, timely use induction  treatment, and improve prognosis

EXPERIENCE WITH TOCILIZUMAB, AN INTERLEUKIN 6 INHIBITOR, USED FOR THE TREATMENT OF GIANT CELL ARTERITIS WITH SEVERE COMORBIDITY

Giant cell arteritis (GCA), formerly known as Horton's disease, is among the most common diseases from a group of systemic vasculitides; its clinical significance is complemented with the potential involvement of the coronary arteries, aorta, and cranial arteries with development of ischemic optic neuropathy if there is no timely treatment that results in rapid and irreversible visual loss. The elderly age of patients is one of the key aspects of GCA. Therefore, the disease is often accompanied by various comorbidities that have considerable impact on the choice of a treatment regimen and limit the use of standard therapy with glucocorticoids (GCs). The complications due to GC treatment can be competitive in severity with GCA, especially in elderly multimorbid patients. Progress in rheumatology due to the introduction of biological agents (BAs) has created the preconditions for the development of a new area of pharmacotherapy for GCA associated with interleukin 6 (IL6) inhibition using tocilizumab (TCZ). According to the results of two randomized placebocontrolled trials (RPCTs), which were published in 2016, the rate of remission with TCZ treatment was significantly higher in patients with GCA than that in the placebo group (p = 0.03–0.0001), as is relapse-free survival after 52 weeks of TCZ treatment (85 and 20%, respectively; p ≤ 0.001), the incidence of serious adverse events (AE) was 14–35%. In 2017, the results of Phase III GiACTA RPCT became the basis for approval of the use of TCZ for the treatment of GCA in the United States and Europe. The authors present their own results of a small prospective study of TCZ in 7 patients with active GCA with severe comorbidity, including multimorbidity, that potentially increases the risk for AE due to GC therapy. The mean age of the patients was 71.3±7.6 years; among them there was one man and 6 women. The administration of TCZ in a monthly dose of 2.3–8.8 mg/kg for 1–10 months with a cumulative dose of 10–58.1 mg/kg could reduce the mean daily dose of prednisolone to 15 (5–32.5) mg, thereby preventing the development or progression of AE, and all the 7 patients could rather rapidly achieve GCA remission. A recurrence after therapy discontinuation was noted in one patient. TCZ treatment was accompanied by serious AE (purulent elbow bursitis); and other two patients had AE a few months after TCZ discontinuation. There were no fatal outcomes. Thus, the presented results suggest that the use of IL6 inhibitors in patients with GCA, including those with severe comorbidity, can be regarded as a potentially effective innovative (off-label) treatment strategy with an acceptable safety profile. The further expansion of an evidence base and the clarification of the medical and economic aspects of TCZ treatment in some groups of GCA will help justify the choice of BAs