Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

Purpose:

The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF]) in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR.

Materials and Methods:

Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control) were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1), interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA) were simultaneously measured using enzyme-linked immunoassay.

Results:

Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05) higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times) compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (P < 0.05) positive correlations were observed between vitreous concentrations of VEGF and IL-17A (r = 0.45), VEGF and IL-8 (r = 0.48), VEGF and IL-4 (r = 0.51), PEDF and IL-17A (r = 0.48), PEDF and IL-8 (r = 0.59), MCP-1 and PEDF (r = 0.72), MCP-1 and IL-8 (r = 0.45), IL-4 and IL-17A (r = 0.65), IL-4 and IL-8 (r = 0.71), IL-8 and IL-17A (r = 0.59).

Conclusions:

Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.     

Postoperative pain due to an occult spinal infection: A case report

BACKGROUNDA high degree of vigilance is warranted for a spinal infection, particularly in a patient who has undergone an invasive procedure such as a spinal injection. The average delay in diagnosing a spinal infection is 2-4 mo. In our patient, the diagnosis of a spinal infection was delayed by 1.5 mo.CASE SUMMARYA 60-year-old male patient with a 1-year history of right-sided lumbar radicular pain failed conservative treatment. Six weeks to prior to surgery he received a spinal injection, which was followed by increasing lumbar radicular pain, weight loss and chills. This went unnoticed and surgery took place with right-sided L4-L5 combined microdiscectomy and foraminotomy via a posterior approach. The day after surgery, the patient developed left-sided lumbar radicular pain. Blood cultures grew Staphylococcus aureus (S. aureus). Magnetic resonance imaging showed inflammatory aberrations, revealing septic arthritis of the left-sided L4/L5 facet joint as the probable cause. Revision surgery took place and S. aureus was isolated from bacteriological samples. The patient received postoperative antibiotic treatment, which completely eradicated the infection.CONCLUSIONThe development of postoperative lower back pain and/or lumbar radicular pain can be a sign of a spinal infection. A thorough clinical and laboratory work-up is essential in the preoperative evaluation of patients with spinal pain.     

Genetics of acute and chronic pancreatitis: An update

Progress made in identifying the genetic susceptibility underlying acute and chronic pancreatitis has benefitted the clinicians in understanding the pathogenesis of the disease in a better way. The identification of mutations in cationic trypsinogen gene(PRSS1 gene; functional gain mutations) and serine protease inhibitor kazal type 1(SPINK1 gene; functional loss mutations) and other potential susceptibility factors in genes that play an important role in the pancreatic secretory functions or response to inflammation during pancreatic injury has changed the current concepts and understanding of a complex multifactorial disease like pancreatitis. An indi-vidual's susceptibility to the disease is governed by ge-netic factors in combination with environmental factors. Candidate gene and genetic linkage studies have iden-tified polymorphisms in cationic trypsinogen(PRSS1), SPINK1, cystic fibrosis trans-membrane conductance regulator(CFTR), Chymotrypsinogen C(CTRC), Ca-thepsin B(CTSB) and calcium sensing receptor(CASR). Individuals with polymorphisms in the mentioned genes and other as yet identified genes are at an enhanced risk for the disease. Recently, polymorphisms in genes other than those involved in "intra-pancreatic trypsin regulatory mechanism" namely Claudin-2(CLDN2) andCarboxypeptidase A1(CPA1) gene have also been iden-tified for their association with pancreatitis. With ever growing number of studies trying to identify the genetic susceptibility in the form of single nucleotide polymor-phisms, this review is an attempt to compile the avail-able information on the topic.     

Variation of cervical sagittal alignment parameters according to gender,pelvic incidence and age

European Spine Journal - The aim was to describe radiographic cervical sagittal alignment variations according to age, gender and pelvic incidence (PI) and to investigate relationships with...     

Enteroendocrine K Cells Exert Complementary Effects to Control Bone Quality and Mass in Mice

The involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K cells were involved in this process. The bone phenotype of transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or enteroendocrine K cells (GIP-DT) was investigated. Mice deficient in GIP secretion exhibited lower bone strength, trabecular bone mass, trabecular number, and cortical thickness, notably due to higher bone resorption. Alterations of microstructure, modifications of bone compositional parameters, represented by lower collagen cross-linking, were also apparent. None of these alterations were observed in GIP-DT mice lacking enteroendocrine K cells, suggesting that another K-cell secretory product acts to counteract GIP action. To assess this, stable analogues of the known K-cell peptide hormones, xenin and GIP, were administered to mature NIH Swiss male mice. Both were capable of modulating bone strength mostly by altering bone microstructure, bone gene expression, and bone compositional parameters. However, the two molecules exhibited opposite actions on bone physiology, with evidence that xenin effects are mediated indirectly, possibly via neural networks. Our data highlight a previously unknown interaction between GIP and xenin, which both moderate gut-bone connectivity. © 2020 American Society for Bone and Mineral Research.     

Non-invasive real-time assessment of hepatic macrovesicular steatosis in liver donors:Hypothesis,design and proof-of-concept study

Macrovesicular Steatosis(MS) is an independent risk factor for adverse post-liver transplant(LT) outcomes. The degree of MS is intimately related to the viability of the liver graft, which in turn is crucial to the success of the operation. An ideal liver graft should have no MS and most centres would find it unacceptable to use a donor liver with severe MS for LT. While a formal liver biopsy is the goldstandard diagnostic test for MS, given the logistical and time constraints it is not universally feasible. Other tests like a frozen section biopsy are plagued by issues of fallibility with reporting and sampling bias making them inferior to a liver biopsy. Hence, the development of an accurate, non-invasive, easy-to-use,handheld, real-time device for quantification of MS would fill this lacuna in the deceased donor selection process. We present the hypothesis, design and proof-ofconcept of a study, which aims to standardise and determine the feasibility and accuracy of a novel handheld device applying the principle of diffuse reflectance spectroscopy for real-time quantification of MS.     

Severe nosocomial pneumonia – emphasis on nebulized tobramycin

ObjectiveTo estimate the efficacy and safety of nebulized tobramycin (NT) as an adjunct to systemic antibiotics in the treatment of severe nosocomial pneumonia (NP).Methods25 mechanically ventilated patients (out of 150 screened) were enrolled in the current observational single-center study. They were randomized to receive either NT (300 mg, BID; group 1, n=15) as an adjunct to systemic antibiotics or for a correction of the regimen of systemic antibiotics (group 2, n=10). The primary outcome measure was resolution of NP and acute respiratory insufficiency. The CPIS, signs of systemic inflammatory response syndrome (SIRS) and oxygenation index were used as objective indicators of the clinical progress.ResultsThe following signs of NT efficacy were detected in 87% of group 1 patients: a decrease of SIRS and CPIS scores within (2.3±1.2) d of NT therapy (P<0.05); decrease of microbes titer to 10³–10⁴ CFU/mL (P<0.05); increase of microbes sensitivity to systemic antibiotics in 40% of patients; positive X-ray dynamics in 60% of patients within (9.0±2.5) d of NT therapy. No serious side effects of NT were observed.ConclusionsAdministration of NT as an adjunct to systemic antibiotics is efficient and safe in 87% of patients with severe NP caused by multiresistant gram-negative bacteria.