Applied physiology: gut microbiota and antimicrobial therapy.

The gut microbiota plays an important role in maintaining human health and in the pathogenesis of several diseases. Antibiotics are among the most commonly prescribed drugs and have a significant impact on the structure and function of the gut microbiota. The understanding that a healthy gut microbiota prevents the development of many diseases has also led to its consideration as a potential therapeutic target. At the same time, any factor that alters the gut microbiota becomes important in this approach. Exercise and antibacterial therapy have a direct effect on the microbiota. The review reflects the current state of publications on the mechanisms of intestinal bacterial involvement in the pathogenesis of cardiovascular, metabolic, and neurodegenerative diseases. The physiological mechanisms of the influence of physical activity on the composition of the gut microbiota are considered. The mechanisms of the common interface between exercise and antibacterial therapy will be considered using the example of several socially important diseases. The aim of the study is to show the physiological relationship between the effects of exercise and antibiotics on the gut microbiota.

Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota.

Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.

Tourette syndrome and obsessive-compulsive disorder: A comprehensive review of structural alterations and neurological mechanisms.

Currently, it is possible to study the pathogenesis of Tourette's syndrome (TS) in more detail, due to more advanced methods of neuroimaging. However, medical and surgical treatment options are limited by a lack of understanding of the nature of the disorder and its relationship to some psychiatric disorders, the most common of which is obsessive-compulsive disorder (OCD). It is believed that the origin of chronic tic disorders is based on an imbalance of excitatory and inhibitory influences in the Cortico-Striato-Thalamo-Cortical circuits (CSTC). The main CSTCs involved in the pathological process have been identified by studying structural and neurotransmitter disturbances in the interaction between the cortex and the basal ganglia. A neurotransmitter deficiency in CSTC has been demonstrated by immunohistochemical and genetic methods, but it is still not known whether it arises as a consequence of genetically determined disturbances of neuronal migration during ontogenesis or as a consequence of altered production of proteins involved in neurotransmitter production. The aim of this review is to describe current ideas about the comorbidity of TS with OCD, the involvement of CSTC in the pathogenesis of both disorders and the background of structural and neurotransmitter changes in CSTC that may serve as targets for drug and neuromodulatory treatments.

Epidemiology of small intestinal bacterial overgrowth.

Small intestinal bacterial overgrowth (SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The presence of SIBO is detected in 33.8% of patients with gastroenterological complaints who underwent a breath test, and is significantly associated with smoking, bloating, abdominal pain, and anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicates the course of a number of diseases and may be of pathogenetic significance in the development of their symptoms. SIBO is significantly associated with functional dyspepsia, irritable bowel syndrome, functional abdominal bloating, functional constipation, functional diarrhea, short bowel syndrome, chronic intestinal pseudo-obstruction, lactase deficiency, diverticular and celiac diseases, ulcerative colitis, Crohn's disease, cirrhosis, metabolic-associated fatty liver disease (MAFLD), primary biliary cholangitis, gastroparesis, pancreatitis, cystic fibrosis, gallstone disease, diabetes, hypothyroidism, hyperlipidemia, acromegaly, multiple sclerosis, autism, Parkinson's disease, systemic sclerosis, spondylarthropathy, fibromyalgia, asthma, heart failure, and other diseases. The development of SIBO is often associated with a slowdown in orocecal transit time that decreases the normal clearance of bacteria from the small intestine. The slowdown of this transit may be due to motor dysfunction of the intestine in diseases of the gut, autonomic diabetic polyneuropathy, and portal hypertension, or a decrease in the motor-stimulating influence of thyroid hormones. In a number of diseases, including cirrhosis, MAFLD, diabetes, and pancreatitis, an association was found between disease severity and the presence of SIBO. Further work on the effect of SIBO eradication on the condition and prognosis of patients with various diseases is required.

Clostridioides difficile infection in patients with nonalcoholic fatty liver disease-current status.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, leading to fibrosis, cirrhosis and hepatocellular carcinoma and also associated with increased cardiovascular disease mortality. The pathogenesis of NAFLD is not fully understood, although NAFLD is thought to be a hepatic form of metabolic syndrome. There is an increasing understanding of the role of microbiota disturbances in NAFLD pathogenesis, and as with many other conditions affecting the microbiota, NAFLD may be a novel risk factor for Clostridioides difficile (C. difficile) colonization (CDC) and C. difficile infection (CDI). CDI is an emerging nosocomial disease, and community-acquired cases of infection are growing, probably due to an increase in CDC rates. The association of NAFLD with CDI has been shown in only 4 studies to date, three of which included less than 1000 patients, although the frequency of NAFLD in these studies was observed in almost 20% of the total patient cohort. These data revealed that NAFLD is a risk factor for CDI development and, moreover, is a risk factor for intestinal complications of CDI. More studies are needed to investigate this association and move forward CDC and CDI screening efforts for this group of patients.

Identifying sex-specific injury predictors as a key factor in maintaining optimal physical activity levels.

BACKGROUND: Optimal physical activity is known to reduce cardiovascular, respiratory and endocrine system diseases and, as a consequence, improve quality of life. An important risk factor for reinjuries during normal exercise is the initial connective tissue pathology. The variety of clinical dysplastic manifestations significantly complicate the timely diagnosis of this comorbidity. AIM: To establish pathognomonic sex-specific dysplasia phenotypes that indicate a particular sensitivity to physical exertion. METHODS: The study involved 117 participants with recurrent musculoskeletal injuries that occurred during normal exercise. There were 67 women (57.26%) and 50 men (42.74%), which made it possible to compare the presence of the identified signs between sexes. A validated questionnaire was used to screen their connective tissue status. RESULTS: Ranking the most commonly revealed dysplasia signs depending on their clinical significance made it possible to establish pathognomonic sex-specific phenotypes that indicated a particular susceptibility to injuries. Individualized programs of optimal physical activity are necessary for men with chest deformities, flat-valgus feet, dolichostenomelia, arachnodactylia, hemorrhoids, abdominal muscle diastasis and recurrent hernias. In women, special sensitivity to physical exertion was associated with a combination of signs such as asthenic body, joint hypermobility, overly soft auricles, thin hyperelastic skin, atrophic striae, telangiectasias and varicose veins. Of particular importance were universal signs such as gothic palate, scoliosis, kyphosis, leg deformities, temporomandibular joint crunching, and moderate to high myopia. CONCLUSION: Participants' connective tissue condition should be considered when designing optimal physical activity programs. Identifying the established sex-specific dysplasia phenotypes will allow timely optimization of training loads, thus reducing the risk of injury.

Anatomical basis for pancreas transplantation via isolated splenic artery perfusion: A literature review.

The variability of vascular anatomy of the pancreas underlines the difficulty of its transplantation. Research regarding the consistency of anatomical variations shows splenic arterial dominance in most cases. This can significantly improve transplantation success. A systematic literature review was performed according to the quality standards described in the AMSTAR measurement tool and the PRISMA guidelines. We valuated existing literature regarding the vascularization and blood perfusion patterns of the pancreas in terms of dominance and variability. The collected data was independently analyzed by two researchers. Variance of vascular anatomy was seen to be underreported in literature, though significant findings have been included and discussed in this study, providing valuable insight into the dynamics of pancreatic perfusion and feasibility of transplantation on several different supplying arteries. The splenic artery (SA) has a high percentage of consistency in all found studies (over 90%). High frequency of anastomoses between arterial pools supplying the pancreas can mediate sufficient blood supply through a dominant vessel, such as the SA, which is present in most cases. Pancreatic transplantation with isolated SA blood supply can provide sufficient arterial perfusion of the pancreas for stable transplant viability due to high anatomical consistency of the SA and vast communications with other arterial systems.

Risk modeling of femoral neck fracture based on geometric parameters of the proximal epiphysis.

BACKGROUND: Fractures of the proximal femur epiphysis are problematic for state health care because they are associated with severe medical and social problems and high morbidity and mortality rates. AIM: To model the potential risk of hip fracture via femur geometric parameters. METHODS: Seventy educational cadaveric femurs from people aged 14 to 80 years, 10 X-ray images from the records of the Human Anatomy Department and 10 X-ray images from the Department of Traumatology, Orthopedics and Disaster Surgery of Sechenov University, were evaluated. The parameters of the fractured bone were measured using images captured with a Canon d60 camera. The projection values of the proximal epiphysis of the cadaveric femurs and geometric parameters of the bones shown in the X-ray images were measured with Autodesk software (AutoCAD 2018). Analysis of the video frames showing bone rotation reveal that the greater trochanter can be inscribed in a parallelepiped, where one of the faces is parallel to the plane of view in the frontal standard projection and is rectangular. The angle of bone rotation obtained by turning the cube corresponded to the angle measured with the second technique. This reliable method of calculating the rotation of the bone relative to the anterior projection was employed in subsequent calculations. The geometric parameters of the femur were measured using X-ray images according to the proposed method. RESULTS: The geometric parameters of 70 femurs were analyzed, and correlation coefficients were calculated. Our measurement results were compared with those reported by other authors. The potential influence of femur geometry on force distribution in the proximal epiphysis of the femur was described, and a 2-dimensional model of the femur epiphysis associated with minimal neck fracture risk was provided. The assessment of the geometric parameters of the femoral epiphysis indicated the greatest risk of a varus fracture of the neck if the angle of the minimal resistance zone (AMRZ) index > 24° and the neck-shaft angle (NSA) < 127.5°. In contrast, the minimum risk was observed at AMRZ < 14° and NSA > 128.87°. CONCLUSION: The proposed method provides the potential femur neck fracture risk based on geometric parameters.

Rare primary mature teratoma of the liver: A case report.

BACKGROUND: Primary liver teratoma is an extremely rare tumor usually affecting children under the age of 3 years. Specific signs of teratoma on ultrasound, computed tomography (CT) or magnetic resonance imaging are lacking, which makes morphology the only diagnostic tool. Misdiagnosis of a mature teratoma may lead to excessive liver resection, whereas misdiagnosis of an immature teratoma may result in spread, causing a life-threatening condition. Consequently, a careful tumor examination is important, and the rarest types of tumors must be accounted for. CASE SUMMARY: We describe a 52 years old female who presented with a solid mass in the left liver lobe. Contrast-enhanced CT and magnetic resonance imaging (MRI) revealed a round, heterogeneous lesion containing a number of fluid areas and areas of calcification in the middle, and the provisional diagnosis was cholangiocarcinoma. The patient underwent resection of liver segment I. Immunohistochemistry analysis of the resected lesion indicated thyroid follicular epithelium; however, the thyroid gland was intact. 10 years prior to presentation the patient underwent a surgery due to mature teratoma of the right ovary, nevertheless the tumor was benign and could not spread to the liver, in addition teratoma of the liver was also benign. This led to the final diagnosis of primary mature liver teratoma. CONCLUSION: Primary hepatic teratoma, including heterotopia of the thyroid gland in the liver, is an extremely rare condition in adults that needs to be considered in the differential diagnosis of solid-cystic neoplasms in the liver and cholangiocarcinoma. This case adds to the limited literature on the patient presentation, clinical workup and management of liver teratomas.

Perihilar cholangiocarcinoma: A different concept for radical resection.

BACKGROUND: Long-term outcomes depend heavily on the possibility of performing radical resection. PURPOSE: To evaluate long-term results in perihilar cholangiocarcinoma (PHC) patients from the perspective of a new understanding of radical resection. METHODS: Consecutive PHC patients who underwent surgical resection at A.V. Vishnevsky Center of Surgery from 2011 to 2018 were retrospectively reviewed. Fifty eight (87.9%) patients underwent hemihepatectomy (14 extended hemihepatectomies), while 2 (3%) underwent extrahepatic bile duct resection only, 6 (9.1%) underwent S4b, and 5 underwent en bloc resection of the extrahepatic bile duct. The influence of the bile duct wedge R status, nodal status, microvascular invasion, microlymphatic invasion, perineural invasion, liver invasion, and surrounding adipose tissue invasion on survival was tested by Cox's models. Survival rates depending on pathological parameter numbers were compared by log-rank tests. RESULTS: Wedge resection, nodal status, microvascular invasion, microlymphatic invasion, perineural invasion, liver invasion, and surrounding adipose tissue invasion served as extended criteria for curability (R+, 1 to 7 parameters). For R0 resection status and R1 resection status (R+1, R+2), 7 and 5 parameters were negative, respectively. For R1+ resection status (R+3, R+4, R+5, R+6, R+7), 3 to 7 parameters were positive. Patients who underwent R0 and R1 resections had 5-year survival rates of 100%; the 1- 2- 3-year survival rates were 63%, 49%, 33% for patients who underwent R1+ resections, respectively. The expanded criteria for determining radical resection levels correlated with long-term outcomes (р = 0.0001). CONCLUSION: The new concept for radical resection can accurately reflect surgical treatment results and contribute to selecting appropriate adjuvant therapies in PHC patients. TRIAL REGISTRATION: The study was carried out in accordance with the framework of the "Multimodal treatment of primary and secondary malignant tumors of the liver and pancreas" (state registration № 315030310062).

Adrenocorticotropic hormone-producing pheochromocytoma: A case report.

INTRODUCTION: Cases of ectopic production of adrenocorticotropic hormone are considerably rare, but persistent in clinical practice. Extremely rare cases of ectopic production, such as via pheochromocytoma secretion, require special clinical attention and prior knowledge. It is important to understand the diagnostic algorithm for identifying ectopic sources of adrenocorticotropic hormone production. PRESENTATION OF CASE: In this clinical vignette we report a patient with a complex variety of clinical symptoms and no discernable cause for hypercriticism. Our clinical case outlines the diagnostic struggles, treatment challenges and surgical tactic for management of a rare ectopic ACTH producing pheochromocytoma. DISCUSSION: Highly variable clinical manifestations of ectopic ACTH producing pheochromocytoma, with typical signs of Cushing's syndrome and pheochromocytoma account for significant diagnostic difficulties and low incidence of verification of this pathology. Correction of symptoms and patient stabilization are of utmost importance throughout treatment. CONCLUSION: ACTH-dependent Cushing's syndrome, caused by a pheochromocytoma is extremely rare, but should be considered as a possible source for ACTH production. The diagnostic challenges of this condition can be met with confidence when a strict search protocol is conducted for detection of ACTH source.