Critical Assessment of the Management of Unstable Angina in a Specialized Cardiology Emergency Room. / Avaliação Crítica do Manejo da Angina Instável em Pronto-Socorro Terciário de Cardiologia.

BACKGROUND: The management of unstable angina (UA) presents a challenge due to its subjective diagnosis and limited representation in randomized clinical trials that inform current practices. OBJECTIVES: This study aims to identify key factors associated with the indication for invasive versus non-invasive stratification in this population and to evaluate factors associated with stratification test results. METHODS: This retrospective cohort study included patients hospitalized with UA over a consecutive 20-month period. To assess factors associated with stratification strategies, patients were divided into invasive stratification (coronary angiography) and non-invasive stratification (other methods) groups. For the analysis of factors related to changes in stratification tests, patients were categorized into groups with or without obstructive coronary artery disease (CAD) or ischemia, as per the results of the requested tests. Comparisons between groups and multiple logistic regression analyses were performed, with statistical significance set at a 5% level. RESULTS: A total of 729 patients were included, with a median age of 63 years and a predominance of males (64.6%). Factors associated with invasive stratification included smoking (p = 0.001); type of chest pain (p < 0.001); "crescendo" pain (p = 0.006); TIMI score (p = 0.006); HEART score (p = 0.011). In multivariate analysis, current smokers (OR 2.23, 95% CI 1.13-4.8), former smokers (OR 2.19, 95% CI 1.39-3.53), and type A chest pain (OR 3.39, 95% CI 1.93-6.66) were independently associated. Factors associated with obstructive CAD or ischemia included length of hospital stay (p < 0.001); male gender (p = 0.032); effort-induced pain (p = 0.037); Diamond-Forrester score (p = 0.026); TIMI score (p = 0.001). In multivariate analysis, only chest pain (type B chest pain: OR 0.6, 95% CI 0.38-0.93, p = 0.026) and previous CAD (OR 1.42, 95% CI 1.01-2.0, p = 0.048) were independently associated. CONCLUSION: The type of chest pain plays a crucial role not only in the diagnosis of UA but also in determining the appropriate treatment. Our results highlight the importance of incorporating pain characteristics into prognostic scores endorsed by guidelines to optimize UA management.

FUNDAMENTO: O manejo da angina instável (AI) é um desafio devido ao seu diagnóstico subjetivo e à sua escassa representação em ensaios clínicos randomizados que determinem as práticas atuais. OBJETIVOS: O objetivo deste estudo é identificar os principais fatores associados à indicação de estratificação invasiva ou não nessa população e avaliar os fatores associados às alterações nos exames de estratificação. MÉTODOS: Coorte retrospectiva de pacientes internados por AI, em um período de 20 meses consecutivos. Para avaliar os fatores associados à estratégia de estratificação, os pacientes foram divididos em estratificação invasiva (cinecoronariografia) e não invasiva (demais métodos). Para análise de fatores relacionados às alterações nos exames de estratificação, os pacientes foram divididos em grupos com ou sem doença arterial coronariana (DAC) obstrutiva ou isquemia, conforme resultados dos exames solicitados. Foram realizadas comparações entre grupos e análise de regressão logística múltipla, com significância estatística definida em um nível de 5%. RESULTADOS: 729 pacientes foram incluídos, com mediana de idade de 63 anos e predomínio do sexo masculino (64,6%). Estiveram associados à estratificação invasiva: tabagismo (p = 0,001); tipo de dor torácica (p < 0,001); dor "em crescendo" (p = 0,006); escore TIMI (p = 0,006); escore HEART (p = 0,011). Na análise multivariada, tabagistas (OR 2,23, IC 95% 1,13-4,8), ex-tabagistas (OR 2,19, IC 1,39-3,53) e dor torácica tipo A (OR 3,39, IC 95% 1,93-6,66) estiveram associados de forma independente. Estiveram associados à DAC obstrutiva ou isquemia: tempo de internação hospitalar (p < 0,001); sexo masculino (p = 0,032); dor desencadeada por esforço (p = 0,037); Diamond-Forrester (p = 0,026); escore TIMI (p = 0,001). Na análise multivariada, apenas dor torácica (dor torácica tipo B: OR 0,6, IC 95% 0,38-0,93, p = 0,026) e DAC prévia (OR 1,42, IC 95% 1,01-2,0, p = 0,048) estiveram associadas de maneira independente. CONCLUSÕES: O tipo de dor torácica desempenha um papel crucial não apenas no diagnóstico da AI, mas também na definição do tratamento adequado. Nossos resultados destacam a importância de incorporar características da dor aos escores prognósticos endossados pelas diretrizes, para otimização do manejo da AI.

Potential Indicators of Intestinal Necrosis in Portal Venous Gas: A Case Report of an 82-Year-Old Woman on Long-Term Hemodialysis with Ascites and Pneumatosis Coli.

BACKGROUND Several factors have been reported as possible predictors of intestinal necrosis in patients with portal venous gas (PVG). We describe potential indicators of intestinal necrosis in PVG identified by contrasting 3 episodes of PVG in a patient on hemodialysis against previously verified factors. CASE REPORT An 82-year-old woman undergoing hemodialysis was admitted to our hospital thrice for acute abdominal pain. On first admission, she was alert, with a body temperature of 36.3°C, blood pressure (BP) of 125/53 mmHg, pulse rate of 60/min, respiratory rate of 18/min, and 100% oxygen saturation on room air. Computed tomography (CT) revealed PVG, intestinal distension, poor bowel wall enhancement, bubble-like pneumatosis in the intestinal wall, and minimal ascites. PVG caused by intestinal ischemia was diagnosed, and she recovered after bowel rest and hydration. Three months later, she had a second episode of abdominal pain. BP was 115/56 mmHg. CT revealed PVG and a slight accumulation of ascites, without pneumatosis in the intestinal wall. She again recovered after conservative measures. Ten months later, the patient experienced a third episode of abdominal pain, with BP of 107/52 mmHg. CT imaging indicated PVG, considerable ascites, and linear pneumatosis of the intestinal walls. Despite receiving conservative treatment, the patient died. CONCLUSIONS A large accumulation of ascites and linear pneumatosis in the intestinal walls could be potential indicators of intestinal necrosis in patients with PVG caused by intestinal ischemia. As previously reported, hypotension was further confirmed to be a reliable predictor of intestinal necrosis.

[A case of COVID-19 associated ischemic colitis].

Ischemic colitis is a disease in which local tissue in the intestinal wall dies to varying degrees due to insufficient blood supply to the colon. Risk factors include cardiovascular disease, diabetes, chronic kidney disease, chronic obstructive pulmonary disease, etc. Typical clinical manifestations of the disease are abdominal pain and hematochezia. The most common locations are the watershed areas of splenic flexure and rectosigmoid junction. The lesions are segmental and clearly demarcated from normal mucosa under endoscopy. The digestive tract is a common extra-pulmonary organ affected by the novel coronavirus, which can be directly damaged by the virus or indirectly caused by virus-mediated inflammation and hypercoagulability. The corona virus disease 2019 (COVID-19) associated intestinal injury can be characterized by malabsorption, malnutrition, intestinal flora shift, etc. CT can show intestinal ischemia, intestinal wall thickening, intestinal wall cystoid gas, intestinal obstruction, ascites, intussusception and other signs. In this study, we reported a case of ischemic colitis in a moderate COVID-19 patient. The affected area was atypical and the endoscope showed diffuse lesions from the cecum to the rectosigmoid junction. No signs of intestinal ischemia were found on imaging and clear thrombosis in small interstitial vessels was found in pathological tissue. Combined with the fact that the patient had no special risk factors in his past history, the laboratory tests indicated elevated ferritin and D-dimer, while the autoantibodies and fecal etiology results were negative, we speculated that the hypercoagulability caused by novel coronavirus infection was involved in the occurrence and development of the disease in this patient. After prolonged infusion support and prophylactic anti-infection therapy, the patient slowly resumed diet and eventually went into remission. Finally, we hoped to attract clinical attention with the help of this case of moderate COVID-19 complicated with ischemic colitis which had a wide range of lesions and a slow reco-very. For patients with abdominal pain and blood in the stool after being diagnosed as COVID-19, even if they are not severe COVID-19, they should be alert to the possibility of ischemic colitis, so as not to be mistaken for gastrointestinal reactions related to COVID-19.

Enhancing 7-dehydrocholesterol suppresses brain ferroptosis and tissue injury after neonatal hypoxia-ischemia.

Neonatal hypoxic-ischemic brain injury (HIBI) results in part from excess reactive oxygen species and iron-dependent lipid peroxidation (i.e. ferroptosis). The vitamin D precursor 7-dehydrocholesterol (7-DHC) may inhibit iron-dependent lipid peroxidation. Primary neurons underwent oxygen and glucose deprivation (OGD) injury and treatment with 7-DHC-elevating medications such as cariprazine (CAR) or vehicle. Postnatal day 9 mice underwent sham surgery or carotid artery ligation and hypoxia and received intraperitoneal CAR. In neurons, CAR administration resulted in significantly increased cell survival compared to vehicle controls, whether administered 48 h prior to or 30 min after OGD, and was associated with increased 7-DHC. In the mouse model, malondialdehyde and infarct area significantly increased after HIBI in the vehicle group, which were attenuated by post-treatment with CAR and were negatively correlated with tissue 7-DHC concentrations. Elevating 7-DHC concentrations with CAR was associated with improved cellular and tissue viability after hypoxic-ischemic injury, suggesting a novel therapeutic avenue.

Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury.

The positive effects of female sex hormones, particularly estradiol and progesterone, have been observed in treatment of various pathologies. Acute kidney injury (AKI) is a common condition in hospitalized patients in which the molecular mechanisms of hormone action are poorly characterized. In this study, we investigated the influence of estradiol and progesterone on renal cells during ischemic injury. We performed both in vivo experiments on female and male rats and in vitro experiments on renal tubular cells (RTCs) obtained from the kidneys of intact animals of different sexes. Since mitochondria play an important role in the pathogenesis of AKI, we analyzed the properties of individual mitochondria in renal cells, including the area, roundness, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening time. We found that pre-treatment with progesterone or estradiol attenuated the severity of ischemia/reperfusion (I/R)-induced AKI in female rats, whereas in male rats, these hormones exacerbated renal dysfunction. We demonstrated that the mPTP opening time was higher in RTCs from female rats than that in those from male rats, which may be one of the reasons for the higher tolerance of females to ischemic injury. In RTCs from the kidneys of male rats, progesterone caused mitochondrial fragmentation, which can be associated with reduced cell viability. Thus, therapy with progesterone or estradiol displays quite different effects depending on sex, and could be only effective against ischemic AKI in females.

H2S alleviates renal ischemia and reperfusion injury by suppressing ERS-induced autophagy.

BACKGROUND: Ischemia/reperfusion injury (IRI) can lead to acute kidney injury and result in high disability and mortality rates. Cystathionine γ-lyase (CSE)-produced hydrogen sulfide (H2S) has been confirmed to play a protective role in renal IRI. While autophagy is involved in renal IRI, its role in the regulation by endoplasmic reticulum stress (ERS) has not been considered. Our study explored the role of CSE/H2S in protecting against renal IRI by regulating ERS-induced autophagy. METHODS: C57/BL6 mice were subjected to 30-min renal ischemia followed by .24-h reperfusion injury (IRI). The H2S donor sodium hydrosulfide hydrate (NaHS) or the CSE inhibitor D,L-propargylglycine (PAG) was injected intraperitoneally (i.p) into the mice. Serum creatinine and urea nitrogen levels were analyzed to evaluate renal function. Renal tubule epithelial cell damage was measured by HE and PAS staining. ERS and microtubule-associated protein light chain 3 (LC3) autophagy (LC3-I to LC3-II conversion) were analyzed by using western blotting. RESULTS: In a C57/BL6 mouse model of acute renal IRI, the application of IRI impaired the renal function, which was accompanied by elevated serum creatinine (P < 0.001) and urea nitrogen levels (P < 0.001). While NaHS pretreatment dramatically attenuated renal IRI, PAG administration exacerbated renal IRI (P < 0.001). Furthermore, NaHS treatment inhibited the ERS-induced increased LC3II/I protein ratio (P < 0.001); increased Beclin-1 protein expression (P < 0.001); PAG pretreatment exacerbated the effects of ERS on both the LC3II/I ratio (P < 0.001) and the Beclin-1 protein expression (P < 0.001). CONCLUSIONS: Our results suggest that the CSE/H2S system is an important therapeutic target for protecting against renal IRI, and it may protect renal tubule epithelial cells from IRI by suppressing ERS-induced autophagy.

Association of EEG Background With Diffusion-Weighted Magnetic Resonance Neuroimaging and Short-Term Outcomes After Pediatric Cardiac Arrest.

BACKGROUND AND OBJECTIVES: EEG and MRI features are independently associated with pediatric cardiac arrest (CA) outcomes, but it is unclear whether their combination improves outcome prediction. We aimed to assess the association of early EEG background category with MRI ischemia after pediatric CA and determine whether addition of MRI ischemia to EEG background features and clinical variables improves short-term outcome prediction. METHODS: This was a single-center retrospective cohort study of pediatric CA with EEG initiated ≤24 hours and MRI obtained ≤7 days of return of spontaneous circulation. Initial EEG background was categorized as normal, slow/disorganized, discontinuous/burst-suppression, or attenuated-featureless. MRI ischemia was defined as percentage of brain tissue with apparent diffusion coefficient (ADC) <650 × 10-6 mm2/s and categorized as high (≥10%) or low (<10%). Outcomes were mortality and unfavorable neurologic outcome (Pediatric Cerebral Performance Category increase ≥1 from baseline resulting in ICU discharge score ≥3). The Kruskal-Wallis test evaluated the association of EEG with MRI. Area under the receiver operating characteristic (AUROC) curve evaluated predictive accuracy. Logistic regression and likelihood ratio tests assessed multivariable outcome prediction. RESULTS: We evaluated 90 individuals. EEG background was normal in 16 (18%), slow/disorganized in 42 (47%), discontinuous/burst-suppressed in 12 (13%), and attenuated-featureless in 20 (22%) individuals. The median percentage of MRI ischemia was 5% (interquartile range 1-18); 32 (36%) individuals had high MRI ischemia burden. Twenty-eight (31%) individuals died, and 58 (64%) had unfavorable neurologic outcome. Worse EEG background category was associated with more MRI ischemia (p < 0.001). The combination of EEG background and MRI ischemia burden had higher predictive accuracy than EEG alone (AUROC: mortality: 0.92 vs 0.87, p = 0.03) or MRI alone (AUROC: mortality: 0.92 vs 0.84, p = 0.02; unfavorable: 0.83 vs 0.73, p < 0.01). Addition of percentage of MRI ischemia to clinical variables and EEG background category improved prediction for mortality (χ2 = 19.1, p < 0.001) and unfavorable neurologic outcome (χ2 = 4.8, p = 0.03) and achieved high predictive accuracy (AUROC: mortality: 0.97; unfavorable: 0.92). DISCUSSION: Early EEG background category was associated with MRI ischemia after pediatric CA. Combining EEG and MRI data yielded higher outcome predictive accuracy than either modality alone. The addition of MRI ischemia to clinical variables and EEG background improved short-term outcome prediction.

Oral post-treatment supplementation with a combination of glutamine, citrulline, and antioxidant vitamins additively mitigates jejunal damage, oxidative stress, and inflammation in rats with intestinal ischemia and reperfusion.

INTRODUCTION: Intestinal ischemia and reperfusion (IIR) injury is closely associated with oxidative stress. Evidence shows that oral supplementation with glutamine and citrulline alleviates IIR-induced jejunal damage. We investigated the effects of a combination of glutamine, citrulline, and antioxidant vitamins on IIR-induced jejunal damage, oxidative stress, and inflammation. METHOD: Male Wistar rats that underwent 60 min of superior mesenteric artery occlusion were orally administered glutamine plus citrulline (GC), vitamin C plus E (CE), or a combination of GC and CE 15 min before and 3, 9, and 21 h after reperfusion. Healthy rats without IIR were used as controls. RESULTS: After reperfusion for 24 h, rats with IIR showed lower levels of red blood cells, hemoglobin, serum glucose, and jejunal DNA and increased white blood cell counts compared to controls (1-way ANOVA with the least significant difference, P < 0.05). The IIR-induced decrease in serum albumin and increase in plasma interleukin-6 and jejunal thiobarbituric acid-reactive substances (TBARS) were significantly reversed by GC and/or CE. The results of the 2-way ANOVA indicated that GC was the main factor that increased jejunal villus height and muscularis DNA, and CE was the main factor that increased jejunal muscularis protein and decreased jejunal proinflammatory cytokine levels and myeloperoxidase activity. In addition, GC and CE are the main factors that decrease plasma proinflammatory cytokine levels and the jejunal apoptotic index. CONCLUSION: Oral post-treatment supplementation with glutamine and citrulline, combined with vitamins C and E, may alleviate IIR-induced oxidative stress, inflammation, and jejunal damage.

Acute superior mesenteric artery syndrome complicated by severe gastric, pancreatic and renal ischaemia.

Superior mesenteric artery syndrome (SMAS) is a rare and potentially life-threatening cause of small bowel obstruction in which the superior mesenteric artery impinges on the third portion of the duodenum. SMAS is typically encountered in patients with low body fat and a history of rapid weight loss and is often diagnosed as a chronic or subacute condition. Here, we describe a case of a healthy adolescent boy without typical SMAS prodromal symptoms presenting with a severe, hyperacute proximal small bowel obstruction due to SMAS. Complications arising from massive gastric and duodenal distension, including gastric, pancreatic and renal ischaemia, necessitated emergent surgical intervention consisting of the duodenojejunostomy bypass with partial gastric resection. The patient recovered without significant lasting consequences.

Transmission of high arterial pressure into renal microvessels during venous-clamping augments ischaemia/reperfusion-induced acute kidney injury in anaesthetized rats.

AIM: In two recent studies, we observed that a 30-min renal vein clamping caused formation of interstitial haemorrhagic congestion in ischaemic and ischaemic/reperfused kidney along with the development of severer acute kidney injury (AKI) than renal artery or pedicle clamping. It was suggested that the transmission of high arterial pressure into renal microvessels during vein occlusion probably causes the occurrence of interstitial haemorrhagic congestion that augments AKI. The present investigation aimed to evaluate this suggestion by reducing renal perfusion pressure (RPP) during renal venous occlusion. METHODS: Anaesthetized male Sprague-Dawley rats were divided into three groups (n = 8), which underwent a 2-h reperfusion period following 30-min bilateral renal venous clamping along with reduced RPP (VIR-rRPP group) or without reduced RPP (VIR group) and an equivalent period after sham-operation (Sham group). RESULTS: The VIR-rRPP group compared with VIR group had lower levels of kidney malondialdehyde and tissue damages as epithelial injuries of proximal tubule and thick ascending limb, vascular congestion, intratubular cast and oedema, along with the less reductions in renal blood flow, creatinine clearance, Na+ -reabsorption, K+ and urea excretion, urine osmolality and free-water reabsorption. Importantly, the formation of intensive interstitial haemorrhagic congestion in the VIR group was not observed in the VIR-rRPP group. CONCLUSION: These results indicate that the transmission of high arterial pressure into renal microvessels during venous occlusion leads to rupturing of their walls and the formation of interstitial haemorrhagic congestion, which has an augmenting impact on ischaemia/reperfusion-induced renal structural damages and haemodynamic, excretory and urine-concentrating dysfunctions.

Mesenteric ischemia in the acute care setting.

ABSTRACT: Mesenteric ischemia is a group of disorders requiring prompt identification, supportive care, and treatment. Chronic mesenteric ischemia can develop into acute mesenteric ischemia, which has high mortality. Acute mesenteric ischemia can be occlusive (caused by arterial embolism, arterial thrombosis, or mesenteric venous thrombosis) or nonocclusive, with treatment depending on the underlying cause.

Dyslipidemia and Efficacy of Remote Ischemic Conditioning in Acute Moderate Ischemic Stroke: A Post Hoc Analysis of the RICAMIS Study.

BACKGROUND: Ischemic conditioning-induced cardioprotection was attenuated by dyslipidemia in some animal and clinical studies, which is not investigated in patients with stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to investigate the association of dyslipidemia on admission with the efficacy of remote ischemic conditioning (RIC). METHODS AND RESULTS: In this analysis, eligible patients were divided into dyslipidemia and normal-lipid groups according to the levels of 4 blood lipid profiles (total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), which were further subdivided into RIC and control subgroups. We analyzed the differences in functional outcome between RIC and control subgroups in dyslipidemia and normal-lipid patients, respectively, and the interaction effects of RIC treatment with blood lipid levels were evaluated. Among 1776 patients from intention-to-treat analysis, 1419 patients with data of blood lipid profiles were included in the final analysis. A significantly higher proportion of modified Rankin Scale score 0 to 1 was identified in the RIC versus control subgroup across the normal-total cholesterol group (69.9% versus 63.5%; P=0.04), normal-triglycerides group (68.1% versus 60.5%; P=0.016), high-low-density lipoprotein cholesterol group (65.7% versus 57.7%; P=0.025), and normal-high-density lipoprotein cholesterol group (68.3% versus 60.5%; P=0.005). Similar statistical trends were found in the high-total cholesterol group (62.8% versus 55.5%; P=0.059), high-triglycerides group (67.8% versus 60.1%; P=0.099), normal-low-density lipoprotein cholesterol group (69.8% versus 63.7%; P=0.105), but no statistical significance was found in the low-high-density lipoprotein cholesterol group (63.4% versus 61%; P=0.705). Furthermore, no significant interaction effect of RIC intervention by blood lipid profiles was found. Similar results were obtained for lipids as continuous variables. CONCLUSIONS: Blood lipids on admission was not associated with the neuroprotective effect of RIC.

From neglect to peril: diabetic ketoacidosis unleashing colonic necrosis and perforation in an adolescent girl with type 1 diabetes mellitus.

OBJECTIVES: Abdominal pain is a common presentation in patients of diabetic ketoacidosis (DKA). However, this pain generally resolves with resolution of dehydration and acidosis. Persistence of abdominal pain even after resolution of ketosis and acidosis should warrant careful reassessment to find evidence of sepsis and concomitant abdominal pathology. CASE PRESENTATION: We report a rare case of type 1 diabetes mellitus in a 15 year old girl diagnosed 6 months ago who presented with mild DKA (pH 7.24, HCO3 - 13.5 mmol/L). Her hospital course was extremely stormy and despite best of our efforts she succumbed due to colonic ischemia and perforation peritonitis. CONCLUSIONS: A high index of suspicion for gut ischemia or perforation should be kept if DKA is associated with septic shock and there is suboptimal response to standard treatment. Mesenteric ischemia can occur in pediatric patients even with mild DKA having very poor diabetes control.

Advances in lung ischemia/reperfusion injury: unraveling the role of innate immunity.

BACKGROUND: Lung ischemia/reperfusion injury (LIRI) is a common occurrence in clinical practice and represents a significant complication following pulmonary transplantation and various diseases. At the core of pulmonary ischemia/reperfusion injury lies sterile inflammation, where the innate immune response plays a pivotal role. This review aims to investigate recent advancements in comprehending the role of innate immunity in LIRI. METHODS: A computer-based online search was performed using the PubMed database and Web of Science database for published articles concerning lung ischemia/reperfusion injury, cell death, damage-associated molecular pattern molecules (DAMPs), innate immune cells, innate immunity, inflammation. RESULTS: During the process of lung ischemia/reperfusion, cellular injury even death can occur. When cells are injured or undergo cell death, endogenous ligands known as DAMPs are released. These molecules can be recognized and bound by pattern recognition receptors (PRRs), leading to the recruitment and activation of innate immune cells. Subsequently, a cascade of inflammatory responses is triggered, ultimately exacerbating pulmonary injury. These steps are complex and interrelated rather than being in a linear relationship. In recent years, significant progress has been made in understanding the immunological mechanisms of LIRI, involving novel types of cell death, the ability of receptors other than PRRs to recognize DAMPs, and a more detailed mechanism of action of innate immune cells in ischemia/reperfusion injury (IRI), laying the groundwork for the development of novel diagnostic and therapeutic approaches. CONCLUSIONS: Various immune components of the innate immune system play critical roles in lung injury after ischemia/reperfusion. Preventing cell death and the release of DAMPs, interrupting DAMPs receptor interactions, disrupting intracellular inflammatory signaling pathways, and minimizing immune cell recruitment are essential for lung protection in LIRI.

Antineutrophil Cytoplasmic Autoantibody-negative Pauci-immune Necrotizing Glomerulonephritis with Plasma Cell-rich Tubulointerstitial Nephritis Complicated with Pleuritis and Digital Ischemia.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) predominantly affects small vessels. Almost all AAV patients are positive for myeloperoxidase- or proteinase 3-ANCA, and ANCA plays a crucial role in the pathogenesis of AAV. We herein report an ANCA-negative AAV patient with pauci-immune necrotizing glomerulonephritis and plasma cell-rich tubulointerstitial nephritis who was complicated with pleuritis and digital ischemia. ANCA-negative AAV is a rare clinical entity that is difficult to diagnose, and pleuritis and digital ischemia are rare manifestations of AAV. An early diagnosis and appropriate treatment are important, as any delay in the diagnosis may worsen the prognosis.

Pax protein depletion in proximal tubules triggers conserved mechanisms of resistance to acute ischemic kidney injury preventing transition to chronic kidney disease.

Acute kidney injury (AKI) is a common condition that lacks effective treatments. In part, this shortcoming is due to an incomplete understanding of the genetic mechanisms that control pathogenesis and recovery. Identifying the molecular and genetic regulators unique to nephron segments that dictate vulnerability to injury and regenerative potential could lead to new therapeutic targets to treat ischemic kidney injury. Pax2 and Pax8 are homologous transcription factors with overlapping functions that are critical for kidney development and are re-activated in AKI. Here, we examined the role of Pax2 and Pax8 in recovery from ischemic AKI and found them upregulated after severe AKI and correlated with chronic injury. Surprisingly, proximal-tubule-selective deletion of Pax2 and Pax8 resulted in a less severe chronic injury phenotype. This effect was mediated by protection against the acute insult, similar to pre-conditioning. Prior to injury, Pax2 and Pax8 mutant mice develop a unique subpopulation of proximal tubule cells in the S3 segment that displayed features usually seen only in acute or chronic injury. The expression signature of these cells was strongly enriched with genes associated with other mechanisms of protection against ischemic AKI including caloric restriction, hypoxic pre-conditioning, and female sex. Thus, our results identified a novel role for Pax2 and Pax8 in mature proximal tubules that regulates critical genes and pathways involved in both the injury response and protection from ischemic AKI.

Vascular neuro-otology: vestibular transient ischemic attacks and chronic dizziness in the elderly.

PURPOSE OF REVIEW: To explore the differential diagnosis of posterior fossa transient ischemic attacks (TIA) associated with vertigo and/or imbalance.To review the contribution of cerebral small vessel (SVD) disease to balance dysfunction and dizziness in the elderly. MAIN FINDINGS: TIAs involving vestibular structures that mediate the vestibulo-ocular and vestibulospinal reflexes remain a diagnostic challenge because they overlap with causes of benign episodic vertigo. Here, we summarize the results of multidisciplinary specialty efforts to improve timely recognition and intervention of peripheral and central vestibular ischemia. More papers confirm that SVD is a major cause of gait disability, falls and cognitive disorder in the elderly. Recent work shows that early stages of SVD may also be responsible for dizziness in the elderly. The predominant location of the white matter changes, in the frontal deep white matter and genu of the corpus callosum, explains the association between cognitive and balance dysfunction in SVD related symptoms. SUMMARY: The evaluation of patients with intermittent vascular vertigo represent a major diagnostic challenge, recent reviews explore the ideal design approach for a multidisciplinary study to increase early recognition and intervention. Hemispheric white matter microvascular ischemia has been the subject of research progress - advanced stages are known to cause gait disorder and dementia but early stages are associated with "idiopathic" dizziness in the elderly.

MULTIPLE MACHINE LEARNING METHODS AND COMPARATIVE TRANSCRIPTOMICS IDENTIFY PIVOTAL GENES FOR ISCHEMIA-REPERFUSION INJURY IN HUMAN DONOR TISSUE UNDERGOING ORTHOTOPIC LIVER TRANSPLANTATION.

ABSTRACT: Background: Hepatic ischemia-reperfusion injury (HIRI) is a major complication affecting patient prognosis during the period after orthotopic liver transplantation (OLT). Although an increasing number of scientists have investigated the molecular biology of ischemia-reperfusion injury (IRI) during OLT in animal and cellular models in recent years, studies using comprehensive and high-quality sequencing results from human specimens to screen for key molecules are still lacking. Aims: The objective of this study is to explore the molecular biological pathways and key molecules associated with HIRI during OLT through RNA sequencing and related bioinformatics analysis techniques. Methods: The study was done by performing mRNA sequencing on liver tissue samples obtained from 15 cases of in situ liver transplantation patients who experienced ischemia and reperfusion injury within 1 year at Guizhou Medical University, and combined with bioinformatics analysis and machine learning methods, we identified the genes and transcription factors that are closely associated with IRI during in situ liver transplantation surgery. Results: There were 877 differentially expressed genes (DEGs) identified in the included liver samples, of which 817 DEGs were upregulated and 60 were downregulated. Functional enrichment analysis revealed significant enrichment of immune-related terms, such as inflammation, defense responses, responses to cytokines, immune system processes, and cellular activation. In addition, core gene enrichment analysis after cytoHubba screening suggested that liver reperfusion injury might be associated with translation-related elements as a pathway together with protein translation processes. Machine learning with the weighted correlation network analysis screening method identified PTGS2, IRF1, and CDKN1A as key genes in the reperfusion injury process. Conclusions: This study demonstrated that the pathways and genomes whose expression is altered throughout the reperfusion process might be critical for the progression of HIRI during OLT.

Incidence, Risk Factors and Management of Postoperative Complications in Horizontal Strabismus Surgery.

OBJECTIVE: To report the incidence, risk factors and management of postoperative complications after horizontal strabismus surgery. DESIGN: Retrospective Cohort study. PARTICIPANTS: The study assessed 1,273 patients with 1,035 cases of exotropia and 238 cases of esotropia, with a minimum 18-month follow-up. METHODS: Retrospective review of strabismus operation patients' medical records included baseline demographics, age at surgery, pre/postoperative visual acuity, and deviation. Complications were categorized as surgical site (infection, scarring, cyst, granuloma, ischemia) and strabismus-related (recurrence, diplopia), with analysis of incidence, risk factors, and management. RESULTS: Among surgical site complications, the incidence of infection, pyogenic granuloma, and anterior segment ischemia were similar between the exotropia (0.3%, 0.3%, 0.2%) and esotropia (0.8%, 0%, 0.4%) groups (p = .221, 0.406, 0.515). In contrast, the esotropia group presented a higher risk of conjunctival inclusion cyst and conjunctival scar than the exotropia group, with incidences of 5.0% vs 2.2% and 6.3% vs 1.3%, respectively (p = .004, <0.001). Regarding strabismus complications, the incidence of early recurrence was not significant between the two groups, with 10.0% in the exotropia group and 10.5% in the esotropia group (p = .553). Older age and poor initial visual acuity were associated with early recurrence (p < .001). The esotropia group had a higher risk of persistent diplopia than the exotropia group, with incidences of 4.2% vs 2.0%, respectively (p = .003). CONCLUSION: Esotropia carries a higher risk of conjunctival inclusion cysts, conjunctival scarring, and persistent diplopia compared to the exotropia group, while both groups exhibit similar rates of early recurrence and other surgical site complications.