Xanthogranulomatous Pyelonephritis Caused by Stenotrophomonas maltophilia—The First Case Report and Brief Review

Xanthogranulomatous pyelonephritis (XGP) represents a rare and severe pathology secondary to chronic urinary obstruction and recurrent infections. Commonly, this condition leads to loss of kidney function, and frequently, surgical approach is the only optional treatment. Proteus mirabilis and Escherichia coli are the most frequent pathogens associated with XGP. The actual changes in the pathogen’s characteristics increased the risk of newly acquired infections once considered opportunistic. Stenotrophomonas malthophilia is one of those agents more related to immunocompromised patients, presenting an increased incidence and modified antibiotic resistance profile in the modern era. This case report presents a healthy female patient with an underlying renal stone pathology diagnosed with XGP related to S. maltophilia urinary infection. After a complete biological and imagistic evaluation, the case was treated as pyonephrosis. Empirical antibiotic administration and a surgical approach were considered. A total nephrectomy was performed, but the patient’s condition did not improve. The patient’s status improved when specific antibiotics were administered based on the bacterial identification and antibiotic susceptibility pattern of drained perinephric fluid. Levofloxacin and Vancomycin were considered the optimal combination in this case. The histopathological examination revealed XGP secondary to chronic renal stone. The present study describes the first case of XGP related to an aerobic Gram-negative pathogen such as S. maltophilia, once considered opportunistic, in an apparently healthy female adult.

Signature laminar distributions of pathology in frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) with either tau (FTLD-tau) or TDP-43 (FTLD-TDP) inclusions are distinct proteinopathies that frequently cause similar frontotemporal dementia (FTD) clinical syndromes. FTD syndromes often display macroscopic signatures of neurodegeneration at the level of regions and networks, but it is unclear if subregional laminar pathology display patterns unique to proteinopathy or clinical syndrome. We hypothesized that FTLD-tau and FTLD-TDP accumulate pathology in relatively distinct cortical layers independent of clinical syndrome, with greater involvement of lower layers in FTLD-tau. The current study examined 170 patients with either FTLD-tau (n = 73) or FTLD-TDP (n = 97) spanning dementia and motor phenotypes in the FTD spectrum. We digitally measured the percent area occupied by tau and TDP-43 pathology in upper layers (I–III), lower layers (IV–VI), and juxtacortical white matter (WM) from isocortical regions in both hemispheres where available. Linear mixed-effects models compared ratios of upper to lower layer pathology between FTLD groups and investigated relationships with regions, WM pathology, and global cognitive impairment while adjusting for demographics. We found lower ratios of layer pathology in FTLD-tau and higher ratios of layer pathology in FTLD-TDP, reflecting lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology, respectively (p < 0.001). FTLD-tau displayed lower ratios of layer pathology related to greater WM tau pathology (p = 0.002) and to earlier involved/severe pathology regions (p = 0.007). In contrast, FTLD-TDP displayed higher ratios of layer pathology not related to either WM pathology or regional severity. Greater cognitive impairment was associated with higher ratios of layer pathology in FTLD-tau (p = 0.018), but was not related to ratios of layer pathology in FTLD-TDP. Lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology are proteinopathy-specific, regardless of clinical syndromes or regional networks that define these syndromes. Thus, patterns of laminar change may provide a useful anatomical framework for investigating how degeneration of select cells and corresponding laminar circuits influence large-scale networks and clinical symptomology in FTLD.

Cytoadherence Properties of Plasmodium knowlesi-Infected Erythrocytes

Plasmodium knowlesi is responsible for zoonotic malaria infections that are potentially fatal. While the severe pathology of falciparum malaria is associated with cytoadherence phenomena by Plasmodium falciparum-infected erythrocytes (IRBC), information regarding cytoadherence properties of P. knowlesi-IRBC remained scarce. Here, we characterized the cytoadherence properties of RBC infected with the laboratory-adapted P. knowlesi A1-H.1 strain. We found that late-stage IRBC formed rosettes in a human serum-dependent manner, and rosettes hampered IRBC phagocytosis. IRBC did not adhere much to unexposed (unstimulated) human endothelial cell lines derived from the brain (hCMEC/D3), lungs (HPMEC), and kidneys (HRGEC). However, after being “primed” with P. knowlesi culture supernatant, the IRBC-endothelial cytoadherence rate increased in HPMEC and HRGEC, but not in hCMEC/D3 cells. Both endothelial cytoadherence and rosetting phenomena were abrogated by treatment of P. knowlesi-IRBC with trypsin. We also found that different receptors were involved in IRBC cytoadherence to different types of endothelial cells. Although some of the host receptors were shared by both P. falciparum- and P. knowlesi-IRBC, the availability of glycoconjugates on the receptors might influence the capacity of P. knowlesi-IRBC to cytoadhere to these receptors.

Total Talar Replacement with Ceramic Implant in Combination with Tibial Component of Ankle Endoprosthesis: A Case Report

Background. Surgical treatment of patients with talus posttraumatic aseptic necrosis and its consequences usually includes tibiotalocalcaneal arthrodesis with various foot joints according to additional indications. This type of surgical treatment has number of significant disadvantages: traumatic surgical technique, permanent loss of movement in functionally significant joints, high risk of non-union, high frequency of residual deformities, the need for long periods of limb immobilization. The question arises: how to overcome the existing disadvantages and improve the results of talus posttraumatic aseptic necrosis treatment? A potential solution to this problem is the total talus endoprosthetics. Clinical case. A 64-year-old patient came to the clinic complaining of pain and deformity of the right foot and ankle area. After the examination, talus posttraumatic aseptic necrosis was diagnosed. The patient underwent ankle joint arthroplasty using total talus ceramic endoprosthesis in combination with the tibial component of the ankle joint endoprosthesis, a course of rehabilitation treatment was performed. Results. The VAS and AOFAS scales indicators showed a significant improvement both in the pain decrease (from 75 mm before surgery to 10 mm after), and in the functional state according to AOFAS by 2.2 times (from 36 to 80 points 20 months after surgery). By the last follow-up the patient could take more than 8000 steps a day. Conclusion. Considering the good clinical result achieved, the ankle joint arthroplasty using total talus ceramic endoprosthesis in combination with the tibial component of the ankle joint endoprosthesis can be considered a promising method of treatment of this severe pathology.

Phenotype from SAMD9 Mutation at 7p21.1 Appears Attenuated by Novel Compound Heterozygous Variants at RUNX2 and SALL1

Sterile α motif domain-containing protein 9 (SAMD9) is a regulatory protein centrally involved in cell proliferation and apoptosis. Mapped to 7p21.1, variants in SAMD9 have been reported in <50 pediatric cases worldwide, typically with early lethality. Germline gain-of-function SAMD9 variants are associated with MIRAGE syndrome (myelodysplasia, infection, restricted growth, adrenal hypoplasia, genital anomalies, and enteropathy). Spalt like transcription factor 1 (SALL1) is a zinc finger transcriptional repressor located at 16q12.1 where only two transcript variants in SALL1 are known. RUNX2 (6p21.1) encodes a nuclear protein with a Runt DNA-binding domain critical for osteoblastic differentiation, skeletal morphogenesis, and serves as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. RUNX2 and SALL1 are thus both “master regulators” of tissue organization and embryo development. Here, we describe exome sequencing and copy number variants in two previously unknown mutations—R824Q in SAMD9, and Q253H in SALL1. A multiexon 3′ terminal duplication of RUNX2 not previously encountered is also reported. This is the first known phenotype assessment for an intersection of all three variants in a healthy 46,XX adult. Focusing on developmental progress, ultrastructural renal anatomy, and selected reproductive aspects, we describe this unique genotype diagnosed incidentally during coronavirus disease 2019 (COVID-19) illness. Individually, disruption in SAMD9, RUNX2, or SALL1 would be expected to give a bleak prognosis. However, this variant convergence appears to dampen severe pathology perhaps by cross-gene silencing of effects normally deleterious when such changes occur alone.

Identifying Key Antigens that Drive Antibody-Mediated Regulation of Chronic Schistosomiasis

<p><b>Chronic schistosomiasis is a spectral illness where patients present with either moderate intestinal (INT) schistosomiasis or severe hepatosplenic schistosomiasis (HS). The different clinical manifestations are associated with the immune response in the patient against schistosome eggs that end up lodged in the liver and other organs. Inbred male CBA/J mice infected with Schistosoma mansoni present with two distinct syndromes, moderate splenomegaly syndrome (MSS) and hypersplenomegaly syndrome (HSS); the pathologies of which parallel human INT and HS forms, respectively. Furthermore, antibody with a cross-reactive idiotype (CRI) is produced in MSS mice and INT patients (Montesano, Freeman et al. 1990a) that is absent in HSS mice and HS patients and is believed to play a protective role against severe pathology.</b></p> <p>Our primary aim was to determine the specific antigens in soluble egg antigen (SEA) that react to protective CRI+ anti-SEA antibodies using the CBA/J mouse model of disease. Using one-dimensional Western blotting, we have shown that the specificities of anti-SEA antibodies present in MSS and HSS forms of schistosomiasis are different. Using two-dimensional differential in-gel electrophoresis, we isolated six spots that were of significant interest as disease-specific candidates and a further six candidates that were infection-specific. Finally, we characterized these antigens using mass spectrometry, where we managed to identify several of these isolated antigens. Our infection-specific antigens can be useful in developing diagnostic tools to identify individuals infected withschistosomiasis, and individuals who are at risk of developing severe disease. Additionally, we found evidence for antigens that are specifically reactive to CRI+ antibodies and these can be used as candidates for the development of a vaccine that can drive the production of these protective antibodies. We also found evidence of CRI- antibody-specific antigens, and further analysis of these antigens may help increase our understanding of severe disease induction in chronic patients. Overall, this study identified several unique candidate antigens that merit further research in developing diagnostic and therapeutic tools, and added to our understanding of helminth interactions in human biology.</p>

Identifying Key Antigens that Drive Antibody-Mediated Regulation of Chronic Schistosomiasis

<p><b>Chronic schistosomiasis is a spectral illness where patients present with either moderate intestinal (INT) schistosomiasis or severe hepatosplenic schistosomiasis (HS). The different clinical manifestations are associated with the immune response in the patient against schistosome eggs that end up lodged in the liver and other organs. Inbred male CBA/J mice infected with Schistosoma mansoni present with two distinct syndromes, moderate splenomegaly syndrome (MSS) and hypersplenomegaly syndrome (HSS); the pathologies of which parallel human INT and HS forms, respectively. Furthermore, antibody with a cross-reactive idiotype (CRI) is produced in MSS mice and INT patients (Montesano, Freeman et al. 1990a) that is absent in HSS mice and HS patients and is believed to play a protective role against severe pathology.</b></p> <p>Our primary aim was to determine the specific antigens in soluble egg antigen (SEA) that react to protective CRI+ anti-SEA antibodies using the CBA/J mouse model of disease. Using one-dimensional Western blotting, we have shown that the specificities of anti-SEA antibodies present in MSS and HSS forms of schistosomiasis are different. Using two-dimensional differential in-gel electrophoresis, we isolated six spots that were of significant interest as disease-specific candidates and a further six candidates that were infection-specific. Finally, we characterized these antigens using mass spectrometry, where we managed to identify several of these isolated antigens. Our infection-specific antigens can be useful in developing diagnostic tools to identify individuals infected withschistosomiasis, and individuals who are at risk of developing severe disease. Additionally, we found evidence for antigens that are specifically reactive to CRI+ antibodies and these can be used as candidates for the development of a vaccine that can drive the production of these protective antibodies. We also found evidence of CRI- antibody-specific antigens, and further analysis of these antigens may help increase our understanding of severe disease induction in chronic patients. Overall, this study identified several unique candidate antigens that merit further research in developing diagnostic and therapeutic tools, and added to our understanding of helminth interactions in human biology.</p>

Experimental Modeling of Osteoporosis in Animals

Experimental studies on animals under conditions of osteopenia and osteoporosis modeling significantly expand the view of the mechanisms of primary and secondary osteoporosis development, help determining the effect of various factors affecting the bone tissue, evaluate the effect of medications, new biomaterials, etc. Osteoporosis is a multifactorial disease; its clinical manifestations depend on a complex interplay of environmental, lifestyle and genetic factors. The review of the literature analyzes the data on the use of animals to assess the features of osteoporosis course when modeling this pathology by surgical and non-surgical methods. The article features the models of osteoporosis which are reproduced on rats and mice being the most accessible objects and the most frequently used by experimenters. The details of modeling the course of such types of osteoporosis as postmenopausal, senile, glucocorticoid-induced, testosterone deficiency (orchiectomy)-induced, immobilization, hypothermia, radiation-induced, etc. are explored. A specific aspect of recent advances in modeling osteoporosis is the creation of transgenic and knockout mice, whose models may be used to detect components of genetic lesions and will certainly contribute to the development of new methods of prevention and therapy of this severe pathology. The similarity and difference of experimental models of osteoporosis describing the pathophysiological changes in humans due to osteoporosis are noted. Emphasis is placed on bioethical norms of working with experimental animals.

Tactics of a general practitioner in case of suspected acute cerebrovascular accident and measures to prevent it

Acute cerebrovascular accident (stroke) is a fairly common severe pathology, which is one of the main causes of death in most countries. Every year in the world, a stroke occurs in 15 million people, of whom about 5 million die, and the same number become disabled. The disease is based on a sudden sharp failure of the normal blood supply to the brain substance due to a rupture or blockage of a blood vessel. Mortality in the first weeks after a stroke can reach 30-35%. Depending on the pathogenesis of the lesion, stroke can be ischemic and hemorrhagic (ischemic occurs about 6 times more often); clinical symptoms will depend on which area of the brain is involved in the pathological process. Predisposing factors include heredity, gender (more often observed in men), age (in elderly age, the risk of stroke increases every year), arterial hypertension, diabetes mellitus, obesity, hypodynamia. Since in 80% of cases after a stroke people become disabled, often unable to take care of themselves, the problem of acute cerebrovascular accident has long passed from the category of purely medical issues to the category of socio-economic ones. The tasks of the general practitioner include the timely identification of factors predisposing to the development of a stroke and minimization of the possible risks of this formidable condition, and in the case of a stroke, active participation in the patient's rehabilitation process.

Characteristics of clinical signs, laboratory and instrumental examinations in various mechanisms of development of type 2 myocardial infarction

Aim. To identify different pathogenetic variants of myocardial infarction type 2 (MI-2). Material and methods. Reviewed 4168 cases of MI admitted in multidisciplinary hospital for 10 years. 353 patients met the criteria for MI-2 without signs of coronary atherothrombosis (CA). In the study group, the features of clinical and laboratory-instrumental manifestations were evaluated. Results. Cases of IM-2 were subdivided into 4 clinical-pathogenic variants (CPV): 1-CPV developed due an increasing in myocardial oxygen demand; 2-CPV, arising from a decrease in the supply of oxygen; 3-CPV associated with local coronary circulation disorder; 4-CPV developed due to the combined oxygen-energy imbalance. In 72 (20.4%) cases, 1-CPV was detected, caused by a hypertensive crisis and/or tachyarrhythmias; 2-CPV observed in 73 (20.68%) patients with hypotension, anemia, microvascular dysfunction, respiratory failure; 3-CPV caused by spasm and embolism of CA was detected in 47 (13.31%) cases; in 161 (45.61%) patients, IM-2 is associated with increased myocardial oxygen demand with reduced oxygen delivery. The gender and risk factors in groups are comparable. The average age of 1-CPV- and 3-CPV-patients was less and amounted to 65.7 and 56.5 versus 70.2 and 73.8 years in the 2-CPV and 4-CPV. Typical clinical and laboratory-instrumental signs of MI were common for patients with 1-CPV and 3-CPV, while 2-CPV and 4-CPV more often had chronic severe pathology, multivessel coronary disorder, and the clinical presentation and ischemic signs were less common. Conclusion. Clinical manifestations and results of examination of patients with MI-2 depend on the mechanism of its development.