[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

The prevalence of accessory renal arteries in sudanese population in Khartoum State: a cross-sectional CT study from 2017 to 2020.

BACKGROUND: Renal artery variations are clinically significant due to their implications for surgical procedures and renal function. However, data on these variations in Sudanese populations are limited. This study aimed to determine the prevalence and characteristics of renal artery variations in a Sudanese population. METHODS: A cross-sectional retrospective study was conducted in Khartoum state from October 2017 to October 2020. A total of 400 Sudanese participants who underwent abdominal CT scans were included. Data on demographic characteristics, kidney measurements, and renal vasculature were collected and analyzed using descriptive statistics and inferential tests. RESULTS: The mean age of participants was 46.7 ± 18 years, with a nearly equal gender distribution. Overall, renal artery variations were present in 11% of participants, with accessory renal arteries observed in 6% of the study population. Among those with accessory vessels, 50% were on the right side, 29.2% on the left, and 20.8% bilateral, distributed across hilar 29.2%, lower polar 29.2%, and upper polar 41.7% regions. No significant associations were found between accessory renal arteries and age or gender (p-value > 0.05). However, participants with accessory renal arteries exhibited significantly narrower width 5.0 ± 1.4 than those with no with accessory renal arteries 5.8 ± 1.1 (p-value 0.002) Early dividing renal arteries were found in 5% of participants, with nearly half being bilateral. No significant associations were found between the presence of early dividing renal arteries and demographic or renal measurements (p-value > 0.05). CONCLUSION: This study provides valuable insights into the prevalence and characteristics of renal artery variations in a Sudanese population. The findings contribute to our understanding of renal anatomy in this demographic and can inform clinical practice and surgical planning, particularly in renal transplantation and other renal procedures.

A Unique Delusion with Depression in Early Stage of Neurocognitive Disorder Due to Vascular Disease: Considerations for Clinicians.

As global aging becomes more prominent, neurocognitive disorders (NCD) incidence has increased. Patients with NCD usually have an impairment in one or more cognitive domains, such as attention, planning, inhibition, learning, memory, language, visual perception, and spatial or social skills. Studies indicate that 50-80% of these adults will develop neuropsychiatric symptoms (NPS), such as apathy, depression, anxiety, disinhibition, delusions, hallucinations, and aberrant motor behavior. The progression of NCD and subsequent NPS requires tremendous care from trained medical professionals and family members. The behavioral symptoms are often more distressing than cognitive changes, causing caregiver distress/depression, more emergency room visits and hospitalizations, and even earlier institutionalization. This signifies the need for early identification of individuals at higher risk of NPS, understanding the trajectory of their NCD, and exploring treatment modalities. In this case report and review, we present an 82-year-old male admitted to our facility for new-onset symptoms of depression, anxiety, and persecutory delusions. He has no significant past psychiatric history, and his medical history is significant for extensive ischemic vascular disease requiring multiple surgeries and two episodes of cerebrovascular accident (CVA). On further evaluation, the patient was diagnosed with major NCD, vascular subtype. We discuss differential diagnoses and development of NPS from NCD in order to explain the significance of more thorough evaluation by clinicians for early detection and understanding of NCD prognosis.

Exertional Lower Extremity Pain in a Triathlete Caused by External Iliac Artery Endofibrosis: A Case Report.

CASE: This report describes a 25-year-old female professional triathlete with right external iliac artery endofibrosis (EIAE) that was definitively diagnosed on contrast-enhanced magnetic resonance images obtained immediately after treadmill running. The EIAE was treated by percutaneous transluminal angioplasty. By 8 weeks after surgery, she had no symptoms of claudication or pain in the right thigh after a 1-hour running session. There has been no recurrence in 1 year postoperatively. CONCLUSION: EIAE is a rare condition and difficult to diagnose in a timely manner because symptoms and radiographic imaging features appear only during intense exercise. Our patient was successfully treated with percutaneous transluminal angioplasty.

Portal vein gas is a sign of intestinal necrosis after pesticide poisoning: a case report.

Portal vein gas accumulation and intestinal pneumatosis are uncommon signs indicating a high mortality risk in cases of intestinal ischemic necrosis. However, the widespread use of computed tomography has led to an increase in detection of benign lesions. We report a case of portal vein gas accumulation resulting from organophosphorus pesticide poisoning. A male patient was brought to the hospital in a comatose state with bilateral pupils that measured 1.0 mm, and he showed shortness of breath and wet rattles in the lungs. A cholinesterase concentration of 214 U/L was detected on an auxiliary examination. The patient was diagnosed with organophosphorus pesticide poisoning and underwent mechanical ventilation, hemoperfusion, and continuous renal replacement therapy according to the poisoning guidelines. On the fifth day, considerable abdominal distension was observed. An abdominal computed tomography scan revealed dilation of the small bowel and ascending colon with fluid and gas accumulation, as well as gas within the intestinal wall and hepatic veins. Although portal vein gas and intestinal pneumatosis are a sign of mortality requiring immediate surgical intervention, an increasing number of benign cases suggests potential benefits of conservative treatment approaches.

Paradox pain sensitivity using cuff pressure or algometer testing in patients with hemophilia.

INTRODUCTION: Pain is a common comorbidity in patients with hemophilia (PwH) due to hemophilic arthropathy. This study aims to explore pain sensitivity in PwH methodologically investigating in cuff pressure testing compared to algometer testing. METHODS: 37 PwH and 35 healthy control subjects (Con) enrolled in this study. Joint health status was assessed. Subjective pain was evaluated using numeric rating scales. Pain sensitivity was measured with pressure algometry and cuff pressure algometry. Pressure pain thresholds of the algometer (PPTa) were measured at knee, ankle joints, and forehead. Subsequently, thresholds of cuff pressure were measured at the left and right lower legs (PPTcuff). In both, lower values represent higher pain sensitivity. RESULTS: PwH exerted a worse joint health status than Con. Pain sensitivity was higher in PwH compared to Con as PPTa of the knee and ankle joints were lower in PwH. No difference was observed in PPTa at the forehead. Contrastingly, lower pain sensitivity was detected in PwH by higher PPTcuff values compared to Con in both legs. CONCLUSION: While PPTa of the knee and ankle joints are lower in PwH, PPTcuff are higher in PwH compared to Con. This reveals a paradox situation, highlighting that PwH experience local, joint- and hemophilic arthropathy-related pain, whereas pain sensitivity of non-affected soft tissue structures is lower. The reasons explaining the PPTcuff results remain elusive but might be explained by coping strategies counteracting chronic joint pain, resulting in lower sensitivity at non-affected structures.

Combination of diuretics for acute heart failure: a protocol for a systematic review of randomised clinical trials with network meta-analysis and trial sequential analysis.

INTRODUCTION: Acute heart failure (AHF) is a critical, costly condition with high mortality rates, affecting millions annually. Despite advances in cardiovascular care, AHF treatment lacks robust evidence. AHF commonly manifests with sudden heart failure symptoms such as pulmonary congestion, and the pathophysiology involves fluid overload. Initial treatment is based on intravenous diuretics typically, but the optimal combination of drugs remains uncertain. METHODS AND ANALYSIS: We will systematically review randomised controlled trials enrolling patients with AHF and volume overload undergoing in-hospital diuretic treatment. We aim to investigate any diuretic intervention. Our search strategy includes the following databases: Embase, Medline, Latin American and Caribbean Health Sciences Literature, Web of Science and the Cochrane Central Register of Controlled Trials. The primary outcome is all-cause mortality. Secondary outcomes are serious adverse events, hospital readmission and kidney failure. Study results reported at the most extended follow-up will be used for all outcomes. If appropriate, we will conduct meta-analysis, trial sequential analysis and network meta-analysis. ETHICS AND DISSEMINATION: No ethics approval is required for this study. The results will be published in a peer-reviewed journal in this field. PROSPERO REGISTRATION NUMBER: CRD42023463979.

Congestive Hepatopathy: Pathophysiology, Workup, and Imaging Findings with Pathologic Correlation.

Liver congestion is increasingly encountered in clinical practice and presents diagnostic pitfalls of which radiologists must be aware. The complex altered hemodynamics associated with liver congestion leads to diffuse parenchymal changes and the development of benign and malignant nodules. Distinguishing commonly encountered benign hypervascular lesions, such as focal nodular hyperplasia (FNH)-like nodules, from hepatocellular carcinoma (HCC) can be challenging due to overlapping imaging features. FNH-like lesions enhance during the hepatic arterial phase and remain isoenhancing relative to the background liver parenchyma but infrequently appear to wash out at delayed phase imaging, similar to what might be seen with HCC. Heterogeneity, presence of an enhancing capsule, washout during the portal venous phase, intermediate signal intensity at T2-weighted imaging, restricted diffusion, and lack of uptake at hepatobiliary phase imaging point toward the diagnosis of HCC, although these features are not sensitive individually. It is important to emphasize that the Liver Imaging Reporting and Data System (LI-RADS) algorithm cannot be applied in congested livers since major LI-RADS features lack specificity in distinguishing HCC from benign hypervascular lesions in this population. Also, the morphologic changes and increased liver stiffness caused by congestion make the imaging diagnosis of cirrhosis difficult. The authors discuss the complex liver macro- and microhemodynamics underlying liver congestion; propose a more inclusive approach to and conceptualization of liver congestion; describe the pathophysiology of liver congestion, hepatocellular injury, and the development of benign and malignant nodules; review the imaging findings and mimics of liver congestion and hypervascular lesions; and present a diagnostic algorithm for approaching hypervascular liver lesions. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Isolated gastric varices associated with antiphospholipid syndrome and protein S deficiency: a case report and review of the literature.

The mortality rate of gastric varices bleeding can reach 20% within 6 weeks. Isolated gastric varices (IGVs) refer to gastric varices without esophageal varices and typically arise as a common complication of left portal hypertension. Although IGVs commonly form in the setting of splenic vein occlusion, the combination of antiphospholipid syndrome and protein S deficiency leading to splenic vein occlusion is rare. We herein present a case of a 28-year-old woman with intermittent epigastric pain and melena. She was diagnosed with antiphospholipid syndrome based on the triad of pregnancy morbidity, unexplained venous occlusion, and positive lupus anticoagulant. Laparoscopic splenectomy and pericardial devascularization were performed for the treatment of IGVs. During the 6-month postoperative follow-up, repeated endoscopy and contrast-enhanced computed tomography revealed disappearance of the IGVs. This is the first description of splenic vein occlusion associated with both antiphospholipid syndrome and protein S deficiency. We also provide a review of the etiology, clinical manifestations, diagnosis, and treatment methods of IGVs.

RhoA/rho kinase pathway activation in age-associated endothelial cell dysfunction and thrombosis.

The small GTPase RhoA and the downstream Rho kinase (ROCK) regulate several cell functions and pathological processes in the vascular system that contribute to the age-dependent risk of cardiovascular disease, including endothelial dysfunction, excessive permeability, inflammation, impaired angiogenesis, abnormal vasoconstriction, decreased nitric oxide production and apoptosis. Frailty is a loss of physiological reserve and adaptive capacity with advanced age and is accompanied by a pro-inflammatory and pro-oxidative state that promotes vascular dysfunction and thrombosis. This review summarises the role of the RhoA/Rho kinase signalling pathway in endothelial dysfunction, the acquisition of the pro-thrombotic state and vascular ageing. We also discuss the possible role of RhoA/Rho kinase signalling as a promising therapeutic target for the prevention and treatment of age-related cardiovascular disease.

Near-Infrared Spectroscopy During Reactive Hyperemia for the Assessment of Lower Limb Vascular Function.

Vascular diseases of the lower limb contribute substantially to the global burden of cardiovascular disease and comorbidities such as diabetes. Importantly, microvascular dysfunction can occur prior to, or alongside, macrovascular pathology, and both potentially contribute to patient symptoms and disease burden. Here, we describe a non-invasive approach using near-infrared spectroscopy (NIRS) during reactive hyperemia, which provides a standardized assessment of lower limb vascular (dys)function and a potential method to evaluate the efficacy of therapeutic interventions. Unlike alternative methods, such as contrast-enhanced ultrasound, this approach does not require venous access or sophisticated image analysis, and it is inexpensive and less operator-dependent. This description of the NIRS method includes representative results and standard terminology alongside the discussion of measurement considerations, limitations, and alternative methods. Future application of this work will improve standardization of vascular research design, data collection procedures, and harmonized reporting, thereby enhancing translational research outcomes in the areas of lower limb vascular (dys)function, disease, and treatment.

In-field use of I-VED electrical impedance sensor for assessing post-dive decompression stress in humans.

Purpose: Ultrasound imaging is commonly used in decompression research to assess venous gas emboli (VGE) post-dive, with higher loads associated with increased decompression sickness risk. This work examines, for the first time in humans, the performance of a novel electrical impedance spectroscopy technology (I-VED), on possible detection of post-dive bubbles presence and arterial endothelial dysfunction that may be used as markers of decompression stress. Methods: I-VED signals were recorded in scuba divers who performed standardized pool dives before and at set time points after their dives at 35-minute intervals for about two hours. Two distinct frequency components of the obtained signals, Low-Pass Frequency-LPF: 0-0.5 Hz and Band-Pass Frequency-BPF: 0.5-10 Hz, are extracted and respectively compared to VGE presence and known flow-mediated dilation trends for the same dive profile for endothelial dysfunction. Results: Subjects with VGE counts above the median for all subjects were found to have an elevated average LPF compared to subjects with lower VGE counts, although this was not statistically significant (p=0.06), as well as significantly decreased BPF standard deviation post-dive compared to pre-dive (p=0.008). Conclusions: I-VED was used for the first time in humans and operated to provide qualitative in-vivo electrical impedance measurements that may contribute to the assessment of decompression stress. Compared to ultrasound imaging, the proposed method is less expensive, not operator-dependent and compatible with continuous monitoring and application of multiple probes. This study provided preliminary insights; further calibration and validation are necessary to determine I-VED sensitivity and specificity.

Antithrombin deficiency caused by SERPINC1 gene mutation in white matter lesions: A case report.

RATIONALE: White matter lesions (WMLs) are structural changes in the brain that manifest as demyelination in the central nervous system pathologically. Vasogenic WMLs are the most prevalent type, primarily associated with advanced age and cerebrovascular risk factors. Conversely, immunogenic WMLs, typified by multiple sclerosis (MS), are more frequently observed in younger patients. It is crucial to distinguish between these 2 etiologies. Furthermore, in cases where multiple individuals exhibit WMLs within 1 family, genetic testing may offer a significant diagnostic perspective. PATIENT CONCERNS: A 25-year-old male presented to the Department of Neurology with recurrent headaches. He was healthy previously and the neurological examination was negative. Brain magnetic resonance imaging (MRI) showed widespread white matter hyperintensity lesions surrounding the ventricles and subcortical regions on T2-weighted and T2 fluid-attenuated inversion recovery images, mimicking immunogenic disease-MS. DIAGNOSES: The patient was diagnosed with a patent foramen ovale, which could explain his headache syndrome. Genetic testing unveiled a previously unidentified missense mutation in the SERPINC1 gene in the patient and his father. The specific abnormal laboratory finding was a reduction in antithrombin III activity, and the decrease may serve as the underlying cause for the presence of multiple intracranial WMLs observed in both the patient and his father. INTERVENTIONS: The patient received percutaneous patent foramen ovale closure surgery and took antiplatelet drug recommended by cardiologists and was followed up for 1 month and 6 months after operation. OUTCOMES: While the lesions on MRI remain unchanging during follow-up, the patient reported a significant relief in headaches compared to the initial presentation. LESSONS: This case introduces a novel perspective on the etiology of cerebral WMLs, suggesting that hereditary antithrombin deficiency (ATD) could contribute to altered blood composition and may serve as an underlying cause in certain individuals with asymptomatic WMLs.

Spectrum of Ischemic Heart Disease Throughout a Woman's Life Cycle.

Ischemic heart disease (IHD) is the leading cause of morbidity and mortality in both genders; however, young women fare the worst, likely reflecting the more complex spectrum of IHD in women when compared to men. Substantial sex-based differences exist in the underlying risk factors, risk enhancers, presentation, diagnosis, and pathophysiology of IHD that are mainly attributed to the influence of female sex hormones. This article reviews the spectrum of IHD including obstructive epicardial coronary artery disease (CAD), myocardial infarction with no obstructive coronary artery disease, ischemia with no obstructive coronary artery disease, spontaneous coronary artery dissection, coronary microvascular dysfunction, vasospastic angina, and coronary thrombosis/embolism that occur in women throughout various stages of their life cycle. We aim to update clinicians on the diagnosis and management of these various types of IHD and highlight where further randomized controlled studies are needed to determine optimal treatment and inform guideline-directed medical therapy.

[Moyamoya disease in adults: treatment methods in modern era]. / Sovremennyi podkhod k lecheniyu angiopatii moyamoya u vzroslykh.

Moyamoya angiopathy is a chronic progressive cerebrovascular disease characterized by stenosis and occlusion of the distal segments of the internal carotid arteries and/or proximal segments of the middle and anterior cerebral arteries, with a gradual compensatory restructuring of the cerebral circulation to the system of the external carotid arteries. Today, the main treatment method for Moyamoya angiopathy is surgical revascularization of the brain. A search and analysis of publications on the treatment of adult patients with Moyamoya angiopathy was carried out in the PubMed and Medscape databases over the past 10 years. We present a case of an adult female patient with a hemorrhagic form of Moyamoya angiopathy stage IV according to J. Suzuki, who underwent staged combined revascularization of both cerebral hemispheres. Surgical revascularization included the creation of a low-flow extra-intracranial shunt combined with a combination of indirect synangiosis. The combination of direct and indirect methods of surgical revascularization enables to achieve the development of an extensive network of collaterals and fully compensate for cerebral circulatory disorders both in the early and late postoperative periods, which is confirmed by instrumental diagnostic data. Combined revascularization is the most effective modern method of treating patients with Moyamoya angiopathy due to the complementary influence of direct and indirect components of revascularization.