IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections.

UNLABELLED: Interleukin (IL)-22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL-22 may also cause inflammation and abnormal cell proliferation. The binding of IL-22 to its receptor is competed by IL-22 binding protein (IL-22BP), which may limit the deleterious effects of IL-22. The role of IL-22 and IL-22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL-22 transcripts and inhibit accumulation of IL22-BP transcripts in schistosome-infected mice, and that schistosome eggs selectively stimulate production of IL-22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL-22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL-22/IL-22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL-22BP, and found that the genotypes, AA, GG of rs6570136 (P = 0.003; odds ratio [OR] = 2), and CC, TT of rs2064501 (P = 0.01; OR = 2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P = 0.0007; OR = 8.2], rs2064501 TT [P = 0.02; OR = 3.1]), and Brazilians (rs6570136 GG [P = 0.003; OR = 26], rs2064501 TC, TT (P = 0.03; OR = 11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV-induced fibrosis and cirrhosis (rs6570136 GG, GA [P = 0.007; OR = 1.7], rs2064501 TT, TC (P = 0.004; OR = 2.4]). CONCLUSIONS: These results provide strong evidence that IL-22 protects against and IL-22BP aggravates liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological modulation of IL-22 BP may be an effective strategy to limit cirrhosis.

C2 versus C3 or C4 as the upper instrumented vertebra for long-segment cervical fusions: a systematic review and meta-analysis.

OBJECTIVE: Selecting C2 versus C3 or C4 (i.e., C3/C4) as the rostral anchoring level in long-segment cervical fusions is a common clinical conundrum. The data regarding proximal failure in long constructs of the cervical spine is scarce. The objective of this study was to systematically review the published literature and perform a meta-analysis of the incidence for proximal adjacent-segment disease (ASD) in the context of long cervical fusions and cervicothoracic fusions ending in C2 versus those ending in the subaxial spine (C3 or C4). METHODS: Using the PRISMA guidelines, the authors performed a search of the PubMed/MEDLINE, Embase/Ovid, and Cochrane Central databases to identify all full-text articles in the English-language literature with the following inclusion criteria: 1) studies including patients with the upper instrumented vertebra (UIV) at C2 versus C3/C4; 2) patients undergoing ≥ 3-level posterior cervical fusion; and 3) indication for surgery of degenerative disc disease, cervical spondylotic myelopathy, or cervical deformity. Studies that were not published in the English language, case reports, review articles, letters to the editor, and meeting abstracts were excluded. A meta-analysis was conducted using a fixed-effects model when I2 values were below 70%. Conversely, when I2 values were equal to or greater than 70%, a random-effects model was used. A funnel plot was used to assess the presence of publication bias. RESULTS: Seven studies consisting of 1215 patients were included in the meta-analysis. There were 403 (32.8%) patients in the C2 UIV group and 812 (67.2%) patients in the C3/C4 UIV group. When the 7 studies were analyzed, the overall rate of reoperation was comparable between the C2 (9.2%) and C3/C4 (9.4%) UIV groups (p = 0.93) but the rate of surgical ASD due to proximal pathology was 1.2% and 3%, respectively (OR 0.36, 95% CI 0.15-0.86; p = 0.02). When comparing between groups, no statistical difference was found regarding the rate of reoperation due to distal pathology or surgical infection. CONCLUSIONS: Long-segment cervical or cervicothoracic constructs that anchor into C2 may have similar complication rates but lower revision rates for proximal ASD than constructs that anchor into the subaxial spine.

Clinical Outcomes and Complication Profile of Spine Surgery in Septuagenarians and Octogenarians: Case Series.

OBJECTIVE: The aging global population presents an increasing challenge for spine surgeons. Advancements in spine surgery, including minimally invasive techniques, have broadened treatment options, potentially benefiting older patients. This study aims to explore the clinical outcomes of spine surgery in septuagenarians and octogenarians. METHODS: This retrospective analysis, conducted at a US tertiary center, included patients aged 70 and older who underwent elective spine surgery for degenerative conditions. Data included the Charlson Comorbidity Index (CCI), ASA classification, surgical procedures, intraoperative and postoperative complications, and reoperation rates. The objective of this study was to describe the outcomes of our cohort of older patients and discern whether differences existed between septuagenarians and octogenarians. RESULTS: Among the 120 patients meeting the inclusion criteria, there were no significant differences in preoperative factors between the age groups (P > 0.05). Notably, the septuagenarian group had a higher average number of fused levels (2.36 vs. 0.38, P = 0.001), while the octogenarian group underwent a higher proportion of minimally invasive procedures (P = 0.012), resulting in lower overall bleeding in the oldest group(P < 0.001). Mobility outcomes were more favorable in septuagenarians, whereas octogenarians tended to maintain or experience a decline in mobility(P = 0.012). A total of 6 (5%) intraoperative complications and 12 (10%) postoperative complications were documented, with no statistically significant differences observed between the groups. CONCLUSIONS: This case series demonstrates that septuagenarians and octogenarians can achieve favorable clinical outcomes with elective spine surgery. Spine surgeons should be well-versed in the clinical and surgical care of older adults, providing optimal management that considers their increased comorbidity burden and heightened fragility.

Indications for Fusion With Intradural Spine Tumor Resection in Adults: A Systematic Review and Meta-analysis.

BACKGROUND: The evidence for instrumented fusion in the setting of degenerative, traumatic, or congenital deformity is well established. Data on fusion indications in intradural spinal tumors (IDST) are scarce and reduced to retrospective studies. The objective of this work is to systematically review the published literature since 2015 and analyze the change of practice patterns for stabilization and fusion after intradural tumor resection in adults. METHODS: A systematic literature review was performed via PubMed with the terms: "intradural spinal tumors", "intramedullary spinal tumors", and "intraspinal tumors". The analysis was limited to adult patients with IDST and studies with more than 10 patients. Data on the proportion of patients who underwent instrumentation and had postoperative deformity was pooled in a meta-analysis. RESULTS: A total of 1073 articles were identified and 47 papers were selected. All the studies were retrospective series and a total of 2473 patients were included. The follow-up ranged from 1 to 96 months, the pooled spinal fixation rate was 6% (95% CI 4.5%-7.6%), the pooled laminoplasty rate was 14.4% (95% CI 5.9%-23%), the pooled rate of postoperative deformity or malalignment in patients with a follow up of at least 6 months was 2.1% (95% CI 1.2%-3%) and just 7 patients were reoperated due to progressive deformity. CONCLUSIONS: Based on existing evidence, the rate of fusion during resection of intradural spinal tumors is low. Prophylactic fixation is often unnecessary and only indicated in unique cases that require extensive bony resection.

Ultrasound findings in urinary shistosomaisis infection in school children in the Gezira State Central Sudan.

To evaluate the ultrasound findings of urinary schistosomiasis in Quran school (Khalwas) children in Gezira State Sudan, we studied all the students from two schools. A total of 103 boys were tested for urinary schistosomiasis using the urine filtration method. Schistosoma haematobium (S. haematobium) eggs were counted. Ultrasound was performed for all the positive subjects. Seventy-three (71%) subjects were positive for S. haematobium. The mean age was 11.3 ± 2.9 years. Sixty-six (90.4%) subjects showed urinary tract abnormalities. The findings revealed the following degrees of wall thickening: 53.0% mild, 18.2% moderate and 21.2% severe. Urinary bladder polyp(s) were noted in 43.3% (single) and 40.9% (multiple) of the subjects, and calcification of the bladder wall was observed in 7.6% subjects. Ureteric dilatation was noted in 38/73 (52.0%), while hydronephrosis was detected in 19/73 (26.3%). The vast majority of urinary tract schistomiasis lesions were in the urinary bladder. Ultrasound is a useful tool for identifying the morbidity of S. haematobium in endemic areas.

Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with schistosomes.

Abnormal fibrosis occurs during chronic hepatic inflammations and is the principal cause of death in hepatitis C virus and schistosome infections. Hepatic fibrosis (HF) may develop either slowly or rapidly in schistosome-infected subjects. This depends, in part, on a major genetic control exerted by genes of chromosome 6q23. A gene (connective tissue growth factor [CTGF]) is located in that region that encodes a strongly fibrogenic molecule. We show that the single nucleotide polymorphism (SNP) rs9402373 that lies close to CTGF is associated with severe HF (P = 2 x 10(-6); odds ratio [OR] = 2.01; confidence interval of OR [CI] = 1.51-2.7) in two Chinese samples, in Sudanese, and in Brazilians infected with either Schistosoma japonicum or S. mansoni. Furthermore, SNP rs12526196, also located close to CTGF, is independently associated with severe fibrosis (P = 6 x 10(-4); OR = 1.94; CI = 1.32-2.82) in the Chinese and Sudanese subjects. Both variants affect nuclear factor binding and may alter gene transcription or transcript stability. The identified variants may be valuable markers for the prediction of disease progression, and identify a critical step in the development of HF that could be a target for chemotherapy.