Keratin 20 positive SDH-deficient renal cell carcinoma: a case report and literature review.

This study aims to broaden the morphological scope of SDH-deficient renal cell carcinoma and to assist clinicians and pathologists in better understanding this entity to prevent misdiagnosis. This study used immunohistochemistry staining and the first-generation sequencing Sanger method for gene detection. It retrospectively analysed the clinical pathology, molecular characteristics, biological behaviour, and treatment information of one case of SDH-deficient renal cell carcinoma. The patient was a 57-year-old female with right back pain for more than 20 days and had no personal or family history of kidney tumours. In addition, the tumour cells had clear boundaries in morphology, and residual normal renal tubules could be seen around them. There were also ossification and adipose tissue around the tumour centre. The tumour cells were arranged in a glandular tubular and cord-like manner. Vacuolar and eosinophilic inclusion bodies could be observed in the cytoplasm. The nucleus was regular, the chromatin distribution was fine, and there were no obvious nucleoli. They were low-grade nuclei. In addition, no atypical mitosis or necrosis could been found. Furthermore, immunohistochemistry staining showed SDHB-negative and keratin 20 -positive tumour. Meanwhile, the first-generation sequencing also pointed out the presence of SDHB gene mutations in the tumour. After 12 months of follow-up, there was no evidence of disease recurrence in the patient. SDH-deficient renal cell carcinoma is a rare tumour associated with SDH gene germline mutations, and suspected cases should undergo SDHB immunohistochemistry staining. Most SDH-deficient renal cell carcinomas have a good prognosis, but undifferentiated cases require long-term follow-up.

Spinal RAMP1-mediated neuropathic pain sensitisation in the aged mice through the modulation of CGRP-CRLR pain signalling.

Pain sensitivity varies depending on both the state and age of an individual. For example, chronic pain is more common in older individuals, but the underlying mechanisms remain unknown. This study revealed that 18-month-old mice (aged) experienced more severe and long-lasting allodynia and hyperalgesia in the chronic constriction injury (CCI)-induced pain state compared to 2-month-old mice. Interestingly, the aged mice had a higher baseline mechanical pain threshold than the adult mice. The expression of spinal receptor-active modification protein 1 (RAMP1), as a key component and regulator of the calcitonin gene-related peptide (CGRP) receptor for nociceptive transmission from the periphery to the spinal cord, was reduced in the physiological state but significantly increased after CCI in the aged mice compared to the adult mice. Moreover, when RAMP1 was knocked down using shRNA, the pain sensitivity of adult mice decreased significantly, and CCI-induced allodynia in aged mice was reduced. These findings suggest that spinal RAMP1 is involved in regulating pain sensitivity in a state- and age-dependent manner. Additionally, interfering with RAMP1 could be a promising strategy for alleviating chronic pain in older individuals.

Identification of Chemical Scaffolds That Inhibit the Mycobacterium tuberculosis Respiratory Complex Succinate Dehydrogenase.

Drug-resistant Mycobacterium tuberculosis is a significant cause of infectious disease morbidity and mortality for which new antimicrobials are urgently needed. Inhibitors of mycobacterial respiratory energy metabolism have emerged as promising next-generation antimicrobials, but a number of targets remain unexplored. Succinate dehydrogenase (SDH), a focal point in mycobacterial central carbon metabolism and respiratory energy production, is required for growth and survival in M. tuberculosis under a number of conditions, highlighting the potential of inhibitors targeting mycobacterial SDH enzymes. To advance SDH as a novel drug target in M. tuberculosis, we utilized a combination of biochemical screening and in-silico deep learning technologies to identify multiple chemical scaffolds capable of inhibiting mycobacterial SDH activity. Antimicrobial susceptibility assays show that lead inhibitors are bacteriostatic agents with activity against wild-type and drug-resistant strains of M. tuberculosis. Mode of action studies on lead compounds demonstrate that the specific inhibition of SDH activity dysregulates mycobacterial metabolism and respiration and results in the secretion of intracellular succinate. Interaction assays demonstrate that the chemical inhibition of SDH activity potentiates the activity of other bioenergetic inhibitors and prevents the emergence of resistance to a variety of drugs. Overall, this study shows that SDH inhibitors are promising next-generation antimicrobials against M. tuberculosis.

Imaging finding of renal masses associated with pathogenic variation in succinate dehydrogenase subunit B gene.

PURPOSE: Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a newly defined, rare subtype of renal cancer, associated with pathogenic variations in the Succinate Dehydrogenase Subunit B (SDHB) gene. Our aim is to investigate the imaging findings of SDHB-associated renal tumors, utilizing cross-sectional and FDG-PET imaging in patients with pathogenic variations in SDHB gene, to facilitate accurate tumor characterization. METHODS: Twenty SDH-deficient tumors from 16 patients with pathogenic variations in SDHB gene were retrospectively evaluated using cross-sectional and FDG-PET imaging. Clinical findings such as demographics, family history, extra-renal findings and metastases were recorded. Tumor imaging characteristics on CT/MRI included were laterality, size, homogeneity, morphology, margins, internal content, T1/T2 signal intensity, enhancement features, and restricted diffusion. RESULTS: Sixteen patients (median age 31 years, IQR 19-41, 8 males) were identified with 68.8 % of patients having a known family history of SDHB variation. 81.3 % of lesions were solitary and majority were solid (86.7 % on CT, 87.5 % on MRI) with well-defined margins in >62.5 % of lesions, without evidence of internal fat, calcifications, or vascular invasion. 100 % of lesions demonstrated restricted diffusion and avid enhancement, with degree >75 % for most lesions on CT and MRI. On FDG-PET, all renal masses showed increased radiotracer uptake. 43.8 % of patients demonstrated extra-renal manifestations and 43.8 % had distant metastasis. CONCLUSION: SDHB-associated RCC is predominantly noted in young patients with no gender predilection. On imaging, SDH-deficient RCC are frequently unilateral, solitary, and solid with well-defined margins demonstrating avid enhancement with variability in enhancement pattern and showing restricted diffusion.

Novel heterocyclic amide derivatives containing a diphenylmethyl moiety: systematic optimizations, synthesis, antifungal activity and action mechanism.

BACKGROUND: The development of fungicides with low cross resistance, high efficacy and low resistance plays a central role in protecting crops, reducing yield losses, improving quality and maintaining global food security. Based on this important role, after a systematic optimization strategy, novel heterocyclic amide derivatives bearing diphenylmethyl fragment were screened, synthesized and verified with the spectrographic and x-ray diffraction analysis. RESULTS: In this study, the aforementioned optimization obtained compound B19 that was measured for antifungal activity against Rhizoctonia solani (median effective concentration, EC50 = 1.11 µg mL-1). Meanwhile, the anti-R. solani protective effect (79.34%) of compound B19 was evaluated in vivo at 100 µg mL-1, which is comparable to that of the control agent fluxapyroxad (80.67%). Thence, morphological observations revealed that compound B19 induced mycelium disruption and shrinking, mitochondrial number reduction and apoptosis acceleration, consistent with the results of the mitochondrial membrane potential and cell membrane permeability. Further investigations found that the potential target enzyme of compound B19 was SDH, which exerted fluorescence quenching dynamic curves similar to that of the commercialized SDHI fluxapyroxad. Additionally, research by molecular docking and MD simulations demonstrated that compound B19 had a similar binding mode acting on the surrounding residues in the SDH active pocket to that offluxapyroxad. CONCLUSION: The above results demonstrated that heterocyclic amide derivatives containing a diphenylmethyl moiety are promising scaffolds for targeting SDH of fungi and provide valuable antifungal leads with the potential to develop new SDH inhibitors. © 2024 Society of Chemical Industry.

Discovery of Novel Nicotinamide Derivatives by a Two-Step Strategy of Azo-Incorporating and Bioisosteric Replacement.

Azobenzene moieties can serve as active fragments in antimicrobials and exert trans/cis conversions of molecules. Herein, a series of novel nicotinamide derivatives (NTMs) were developed by employing a two-step strategy, including azo-incorporating and bioisosteric replacement. Azo-incorporation can conveniently provide compounds that can be easily optically interconverted between trans/cis isomers, enhancing the structural diversity of azo compounds. It is noteworthy that the replacement of the azo bond with a 1,2,4-oxadiazole motif through further bioisosteric replacement led to the discovery of a novel compound, NTM18, which made a breakthrough in preventing rice sheath blight disease. A control effect value of 94.44% against Rhizoctonia solani could be observed on NTM18, while only 11.11% was determined for boscalid at 200 mg·L-1. Further mechanism validations were conducted, and the molecular docking analysis demonstrated that compound NTM18 might have a tight binding with SDH via an extra π-π interaction between the oxadiazole ring and residue of D_Y586. This work sets up a typical case for the united applications of azo-incorporating and bioisosteric replacement in fungicide design, posing an innovative approach in structural diversity-based development of pesticides.

Amitriptyline and duloxetine attenuate activities of superficial dorsal horn neurons in a rat reserpine-induced fibromyalgia model.

Fibromyalgia (FM) is an intractable disease with a chief complaint of chronic widespread pain. Amitriptyline (AMI) and duloxetine (DLX), which are antidepressant drugs, have been reported to ameliorate pain in patients with FM and pain-related behaviors in several rodent models of FM. However, the mechanisms of action of AMI and DLX are not yet fully understood. Here, we examined the effects of these drugs on the responsiveness of superficial dorsal horn (SDH) neurons in the spinal cord, using a rat FM model developed by injecting a biogenic amine depleter (reserpine). Extracellular recordings of SDH neurons in vivo demonstrated that bath application of AMI and DLX at concentrations of 0.1-1.0 mM on the dorsal surface of the spinal cord markedly suppressed spontaneous discharge and von Frey filament-evoked mechanical firing in SDH neurons. The suppression induced by the drugs was noted in a concentration-dependent manner and the suppressive effects resolved after washing the spinal cord surface. These results show that SDH neurons are the site of action for AMI and DLX in a rat reserpine-induced FM model. Spinal mechanisms may underlie the therapeutic effects of these drugs in patients with FM.

ß-Cyclodextrin-optimized supramolecular nanovesicles enhance the droplet/foliage interface interactions and inhibition of succinate dehydrogenase (SDH) for efficient treatment of fungal diseases.

BACKGROUND: Plant fungal diseases present a major challenge to global agricultural production. Despite extensive efforts to develop fungicides, particularly succinate dehydrogenase inhibitors (SDHIs), their effectiveness is often limited by poor retention of fungicide droplets on hydrophobic leaves. The off-target losses and unintended release cause fungal resistance and severe environmental pollution. RESULTS: To update the structure of existing SDHIs and synchronously realize the efficient utilization, we have employed a sophisticated supramolecular strategy to optimize a structurally novel SDH inhibitor (AoH25), creating an innovative supramolecular SDH fungicide (AoH25@ß-CD), driven by the host-guest recognition principle between AoH25 and ß-cyclodextrin (ß-CD). Intriguingly, AoH25@ß-CD self-assembles into biocompatible supramolecular nanovesicles, which reinforce the droplet/foliage (liquid-solid) interface interaction and the effective wetting and retention on leaf surfaces, setting the foundation for enhancing fungicide utilization. Mechanistic studies revealed that AoH25@ß-CD exhibited significantly higher inhibition of SDH (IC50 = 1.56 µM) compared to fluopyram (IC50 = 244.41 µM) and AoH25 alone (IC50 = 2.29 µM). Additionally, AoH25@ß-CD increased the permeability of cell membranes in Botryosphaeria dothidea, facilitating better penetration of active ingredients into pathogenic cells. Further experimental outcomes confirmed that AoH25@ß-CD was 88.5% effective against kiwifruit soft rot at a low-dose of 100 µg mL-1, outperforming commercial fungicides such as fluopyram (52.4%) and azoxystrobin (65.4%). Moreover, AoH25@ß-CD showed broad-spectrum bioactivity against oilseed rape sclerotinia, achieving an efficacy of 87.2%, outstripping those of fluopyram (48.7%) and azoxystrobin (76.7%). CONCLUSION: This innovative approach addresses key challenges related to fungicide deposition and resistance, improving the bioavailability of agricultural chemicals. The findings highlight AoH25@ß-CD as a novel supramolecular SDH inhibitor, demonstrating its potential as an efficient and sustainable solution for plant disease management.

Management of bilateral head and neck paragangliomas at a single-institution across four decades.

BACKGROUND: Bilateral head and neck paragangliomas (HNPGLs) require nuanced management to balance tumor control with functional preservation. METHODS: All patients seen at a single-institution for bilateral paraganglioma between 1983 and 2023 were retrospectively reviewed. Demographics, genetic testing results, and tumor characteristics were analyzed and compared to treatment modality and cranial nerve outcomes. RESULTS: There were 49 patients with 116 tumors (90 carotid body tumors [CBTs], 15 vagal paragangliomas [VPs], and 11 jugular paragangliomas [JPs]). Twenty-six patients had SDH pathologic variants (PV). Surgical management was more commonly utilized in younger patients (OR: 0.97, 95% CI: 0.950-0.992) and for JPs (OR: 9, 95% CI: 1.386-58.443). In surgical cases, CBTs had a lower risk of postoperative cranial nerve deficits compared to JPs and VPs (OR: 0.095, 95% CI: 0.013-0.692). CONCLUSIONS: Younger patients with bilateral HNPGLs, especially those with JP and CBT, are more often treated with surgery. CBTs have lowest risk of cranial nerve deficits after surgery.

A Case of Spontaneous Atraumatic Subdural Hematoma Without Known Precipitating Factors.

Subdural hematoma (SDH) is a disease commonly seen in both the emergency department and the intensive care unit. Here, we present a case of a woman who developed acute SDH, without any precipitating trauma nor predisposing risk factors. She was managed with hemicraniectomy and SDH evacuation, with subsequent cranioplasty. Routine surveillance imaging found a subsequent, small, and again idiopathic SDH. Comprehensive hematologic workup demonstrated no evidence of coagulopathy. To our knowledge, there are minimal prior case reports published in the literature regarding idiopathic, unprovoked SDH.

Discovery of Novel Acethydrazide-Containing Flavonol Derivatives as Potential Antifungal Agents.

In this study, a series of novel hydrazide-containing flavonol derivatives was designed, synthesized, and evaluated for antifungal activity. In the in vitro antifungal assay, most of the target compounds exhibited potent antifungal activity against seven tested phytopathogenic fungi. In particular, compound C32 showed the best antifungal activity against Rhizoctonia solani (EC50 = 0.170 µg/mL), outperforming carbendazim (EC50 = 0.360 µg/mL) and boscalid (EC50 = 1.36 µg/mL). Compound C24 exhibited excellent antifungal activity against Valsa mali, Botrytis cinerea, and Alternaria alternata with EC50 values of 0.590, 0.870, and 1.71 µg/mL, respectively. The in vivo experiments revealed that compounds C32 and C24 were potential novel agricultural antifungals. 3D quantitative structure-activity relationship (3D-QSAR) models were used to analyze the structure-activity relationships of these compounds. The analysis results indicated that introducing appropriate electronegative groups at position 4 of a benzene ring could effectively improve the anti-R. solani activity. In the antifungal mechanism study, scanning electron microscopy and transmission electron microscopy analyses revealed that C32 disrupted the normal growth of hyphae by affecting the structural integrity of the cell membrane and cellular respiration. Furthermore, compound C32 exhibited potent succinate dehydrogenase (SDH) inhibitory activity (IC50 = 8.42 µM), surpassing that of the SDH fungicide boscalid (IC50 = 15.6 µM). The molecular dynamics simulations and docking experiments suggested that compound C32 can occupy the active site and form strong interactions with the key residues of SDH. Our findings have great potential for aiding future research on plant disease control in agriculture.

Itaconate and dimethyl itaconate upregulate IL-6 production in the LPS-induced inflammation in mice.

Itaconate is one of the most studied immunometabolites produced by myeloid cells during inflammatory response. It mediates a wide range of anti-inflammatory and immunoregulatory effects and plays a role in a number of pathological states, including autoimmunity and cancer. Itaconate and its derivatives are considered potential therapeutic agents for the treatment of inflammatory diseases. While immunoregulatory effects of itaconate have been extensively studied in vitro and using knockout mouse models, less is known about how therapeutic administration of this metabolite regulates inflammatory response in vivo. Here, we investigate the immunoregulatory properties of exogenous administration of itaconate and its derivative dimethyl itaconate in a mouse model of lipopolysaccharide-induced inflammation. The data show that administration of itaconate or dimethyl itaconate controls systemic production of multiple cytokines, including increased IL-10 production. However, only dimethyl itaconate was able to suppress systemic production of IFNγ and IL-1ß. In contrast to in vitro data, administration of itaconate or dimethyl itaconate in vivo resulted in systemic upregulation of IL-6 in the blood. Electrophilic stress due to itaconate or dimethyl itaconate was not responsible for IL-6 upregulation. However, inhibition of succinate dehydrogenase with dimethyl malonate also resulted in elevated systemic levels of IL-6 and IL-10. Taken together, our study reports a novel effect of exogenous itaconate and its derivative dimethyl itaconate on the production of IL-6 in vivo, with important implications for the development of itaconate-based anti-inflammatory therapies.

Newer treatment paradigm improves outcomes in the most common neurosurgical disease of the elderly: a literature review of middle meningeal artery embolization for chronic subdural hematoma.

Chronic subdural hematoma (cSDH) is one of the most prevalent neurosurgical diseases, especially in the elderly. Yet, its incidence is predicted to increase further, paralleling the growth of the geriatric population. While surgical evacuation is technically straightforward, it is associated with significant morbidity and mortality. In fact, 30% of patients are expected to have hematoma recurrence and to need repeat surgical evacuation, and 20% of patients are expected to lose independence and require long-term care. A pathophysiology more complex than originally presumed explains the disappointing results observed for decades. At its core, the formation of microcapillaries and anastomotic channels with the middle meningeal artery (MMA) perpetuates a constant cycle resulting in persistence of hematoma. The rationale behind MMA embolization is simple: to stop cSDH at its source. Over the last few years, this "newer" option has been heavily studied. It has shown tremendous potential in decreasing hematoma recurrence and improving neurological outcomes. Whether combined with surgical evacuation or performed as the only treatment, the scientific evidence to its benefits is unequivocal. Here, we aimed to review cSDH in the elderly and discuss its more recent treatment options with an emphasis on MMA embolization.

Quercetin induces itaconic acid-mediated M1/M2 alveolar macrophages polarization in respiratory syncytial virus infection.

BACKGROUND: Quercetin has received extensive attention for its therapeutic potential treating respiratory syncytial virus (RSV) infection diseases. Recent studies have highlighted quercetin's ability of suppressing alveolar macrophages (AMs)-derived lung inflammation. However, the anti-inflammatory mechanism of quercetin against RSV infection still remains elusive. PURPOSE: This study aims to elucidate the mechanism about quercetin anti-inflammatory effect on RSV infection. METHODS: BALB/c mice were intranasally infected with RSV and received quercetin (30, 60, 120 mg/kg/d) orally for 3 days. Additionally, an in vitro infection model utilizing mouse alveolar macrophages (MH-S cells) was employed to validate the proposed mechanism. RESULTS: Quercetin exhibited a downregulatory effect on glycolysis and tricarboxylic acid (TCA) cycle metabolism in RSV-infected AMs. However, it increased itaconic acid production, a metabolite derived from citrate through activating immune responsive gene 1 (IRG1), and further inhibiting succinate dehydrogenase (SDH) activity. While the suppression of SDH activity orchestrated a cascading downregulation of Hif-1α/NLRP3 signaling, ultimately causing AMs polarization from M1 to M2 phenotypes. CONCLUSION: Our study demonstrated quercetin stimulated IRG1-mediated itaconic acid anabolism and further inhibited SDH/Hif-1α/NLRP3 signaling pathway, which led to M1 to M2 polarization of AMs so as to ameliorate RSV-induced lung inflammation.

Fungicide Sensitivity Profile of Pyrenophora teres f. teres in Field Population.

Pyrenophora teres f. teres (Ptt) is a severe pathogen to spring barley in Northern Europe. Ptt with relevant mutations in fungicide target proteins, sterol 14α-demethylase (CYP51A), cytochrome b (Cyt b), and succinate dehydrogenase (SDH) would put efficient disease control at risk. In the growing seasons of 2021 and 2022, 193 Ptt isolates from Estonia were analysed. In this study, mutation detection and in vitro fungicide sensitivity assays of single-spore isolates were carried out. Reduced sensitivity phenotype to mefentrifluconazole was evident in Ptt isolates with a F489L mutation in CYP51A or with 129 bp insert in the Cyp51A gene-promoter region. However, sensitivity to a prothioconazole-desthio remained high regardless of these molecular changes. The Ptt population was mostly sensitive to bixafen, fluxapyroxad, pyraclostrobin, and azoxystrobin. The sensitivity of fluxapyroxad and bixafen has been affected by two mutations, C-S135R and D-H134R, found in SDH subunits. The F129L mutation in Cyt b influenced azoxystrobin but not pyraclostrobin sensitivity. In total, 30 isolates from five fields had relevant mutations in three target protein genes simultaneously. Most of these isolates had a reduced sensitivity phenotype to mefentrifluconazole, fluxapyroxad, and azoxystrobin, while sensitivity to other tested fungicides remained high. Furthermore, possible sexual reproduction may enhance the pathogen's fitness and help it adapt to fungicides.

Mitochondrial membrane transporters as attractive targets for the fermentative production of succinic acid from glycerol in Saccharomyces cerevisiae.

Previously, we reported an engineered Saccharomyces cerevisiae CEN.PK113-1A derivative able to produce succinic acid (SA) from glycerol with net CO2 fixation. Apart from an engineered glycerol utilization pathway that generates NADH, the strain was equipped with the NADH-dependent reductive branch of the TCA cycle (rTCA) and a heterologous SA exporter. However, the results indicated that a significant amount of carbon still entered the CO2-releasing oxidative TCA cycle. The current study aimed to tune down the flux through the oxidative TCA cycle by targeting the mitochondrial uptake of pyruvate and cytosolic intermediates of the rTCA pathway, as well as the succinate dehydrogenase complex. Thus, we tested the effects of deletions of MPC1, MPC3, OAC1, DIC1, SFC1, and SDH1 on SA production. The highest improvement was achieved by the combined deletion of MPC3 and SDH1. The respective strain produced up to 45.5 g/L of SA, reached a maximum SA yield of 0.66 gSA/gglycerol, and accumulated the lowest amounts of byproducts when cultivated in shake-flasks. Based on the obtained data, we consider a further reduction of mitochondrial import of pyruvate and rTCA intermediates highly attractive. Moreover, the approaches presented in the current study might also be valuable for improving SA production when sugars (instead of glycerol) are the source of carbon.

Middle meningeal artery embolization reduces recurrence following surgery for septated chronic subdural hematomas.

BACKGROUND: Septated chronic subdural hematomas (cSDH) have high rates of recurrence despite surgical evacuation. Middle meningeal artery embolization (MMAE) has emerged as a promising adjuvant for secondary prevention, yet its efficacy remains ill-defined. METHODS: This is a retrospective review of septated cSDH cases treated at our institution. The surgery-only group was derived from cases performed before 2018, and the surgery+MMAE group was derived from cases performed 2018 or later. The primary outcome was reoperation rate. Secondary outcomes were recurrence, change in hematoma thickness, and midline shift. RESULTS: A total of 34 cSDHs in 28 patients (surgery+MMAE) and 95 cSDHs in 83 patients (surgery-only) met the inclusion criteria. No significant difference in baseline characteristics between groups was identified. The reoperation rate was significantly higher in the surgery-only group (n = 16, 16.8%) compared with the surgery+MMAE cohort (n = 0, 0.0%) (p=0.006). A reduced incidence of recurrence (p=0.011) was also seen in the surgery+MMAE group. CONCLUSIONS: MMAE for septated cSDH was found to be highly effective in preventing recurrence and reoperation. MMAE is an adjunct to surgical evacuation may be of particular benefit in this patient cohort.

Case report: Concurrent low-volume subdural hematoma and ipsilateral ischemic stroke presenting as capsular warning syndrome: a complex case with anticoagulation dilemma and dual pathology.

Background: The simultaneous emergence of low-volume subdural hematoma and ipsilateral ischemic stroke in an atrial fibrillation patient who is under anticoagulation therapy is a rare and intricate clinical case. This report accentuates the diagnostic and treatment complexities associated with these consecutive neurological conditions. Case presentation: An 83 years-old male patient initially presented with acute dyspnea, raising the suspicion of pulmonary embolism. After exclusion of pulmonary embolism through CT angiography, the patient experienced a sudden onset of left-sided hemiparesis without prior history of head trauma but with chronic intake of apixaban due to atrial fibrillation. Subsequent cranial CT tomography revealed a small right parietal subdural hematoma. After reversal of the anticoagulation therapy, surgical evacuation of the subdural hematoma was successfully performed. However, in the postoperative period, the patient developed new neurological symptoms that could not be explained by the reduced size of the subdural hematoma on a follow-up CT scan. Cranial MRI revealed the coexistence of acute ischemic stroke in the right corona radiata. The recent surgical procedure precluded guideline-recommended stroke treatment. Discussion: This case underscores the complexities of diagnosing and treating concomitant small volume subdural hematoma and ischemic stroke, especially if the latter occurs in the corona radiata resulting in fluctuating symptoms known as "capsular warning syndrome." Reversal and secondary discontinuation of anticoagulant therapy for surgical intervention highlight the inherent risk of thrombotic events in anticoagulated patients. The development of tailored treatment strategies requires a multidisciplinary approach, and further research and guidelines are required in similar complex scenarios. Conclusion: The presence of both a small subdural hematoma and an ipsilateral ischemic stroke presenting as capsular warning syndrome in an anticoagulated patient highlights the intricacy of their care. This case calls for a comprehensive and collaborative strategy to address complicated clinical scenarios.

Social determinants of health rather than race impact health-related quality of life in 10-year-old children born extremely preterm.

Background: Reducing healthcare disparities among children is extremely important given the potential impact of these disparities on long-term health-related quality of life (HRQL). Race and parental socioeconomic status (SES) are associated with child HRQL, but these associations have not been studied in infants born extremely preterm (EP), a population at increased risk for physical, cognitive, and psychosocial impairments. Achieving health equity for infants born EP across their life course requires identifying the impact of racism and SES on HRQL. Objective: We aimed to evaluate the association between self-reported maternal race, SES factors, and HRQL among 10-year-old children born EP. Design/methods: Participants were identified from an ongoing multicenter prospective longitudinal study of Extremely Low Gestational Age Newborns (ELGAN Study), born between 2002 and 2004, and evaluated at 10 years of age using the Pediatric quality of life (QoL) Inventory completed by their parent or guardian, assessing physical, emotional, social, school, and total (composite) QoL domains. Multivariable regression models were used to evaluate the relationship between QoL scores and self-identified maternal race, adjusting for SES factors (education level, marital status, and public insurance). Results: Of 1,198 study participants who were alive at 10 years of age, 863 (72.0%) were evaluated at 10 years of age. Differences in mean 10-year QoL scores across racial groups were observed and were significant on univariate analysis. However, these associations attenuated when adjusted for the marital status, public insurance status, and education status of mothers. A comparison of children with English as the primary language spoken at home vs. any other language revealed a significant difference only in school QoL, in which non-English language was associated with more favorable school QoL scores. Conclusions: Among 10-year-old children born EP, differences in parent-reported QoL were associated with maternal SES factors but not with race. Our results suggest that interventions designed to improve the SES of mothers may enhance the QoL of children born EP. Furthermore, these results underscore that race is a social construct, rather than a biological variable, as we work toward greater equity in care provision.