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Radiology and Oncology Jun 2024This study aimed to assess Ga-DOTA-TATE (-TOC) PET/CT quantitative parameters in monitoring and predicting everolimus response in neuroendocrine tumor (NET) patients...
BACKGROUND
This study aimed to assess Ga-DOTA-TATE (-TOC) PET/CT quantitative parameters in monitoring and predicting everolimus response in neuroendocrine tumor (NET) patients with hepatic metastases (NELM).
PATIENTS AND METHODS
This retrospective analysis included 29 patients with 62 target lesions undergoing everolimus treatment and pre-therapy, and follow-up Ga-DOTA-TATE (-TOC) PET/CT scans. Response evaluation utilized progression-free survival (PFS) categorized as responders (R; PFS > 6 months) and non-responders (NR; PFS ≤ 6 months). Lesion size and density, along with maximum and median standardize uptake value (SUV) in target lesions, liver, and spleen were assessed. Tumor-to-spleen (T/S) and tumor-to-liver (T/L) ratios were calculated, including the tumor-to-spleen (T/S) ratio and tumor-to-liver (T/L) ratio (using SUVmax/SUVmax, SUVmax/SUVmean, and SUVmean/SUVmean).
RESULTS
PET/CT scans were acquired 19 days (interquartile range [IQR] 69 days) pre-treatment and 127 days (IQR 74 days) post-starting everolimus. The overall median PFS was 264 days (95% CI: 134-394 days). R exhibited significant decreases in Tmax/Lmax and Tmean/Lmax ratios compared to NR (p = 0.01). In univariate Cox regression, Tmean/Lmax ratio was the sole prognostic parameter associated with PFS (HR 0.5, 95% CI 0.28-0.92, p = 0.03). Percentage changes in T/L and T/S ratios were significant predictors of PFS, with the highest area under curve (AUC) for the percentage change of Tmean/Lmax (AUC = 0.73). An optimal threshold of < 2.5% identified patients with longer PFS (p = 0.003). No other imaging or clinical parameters were predictive of PFS.
CONCLUSIONS
This study highlights the potential of quantitative SSTR-PET/CT in predicting and monitoring everolimus response in NET patients. Liver metastasis-to-liver parenchyma ratios outperformed size-based criteria, and Tmean/Lmax ratio may serve as a prognostic marker for PFS, warranting larger cohort investigation.
PubMed: 38861687
DOI: 10.2478/raon-2024-0032 -
Proceedings of the National Academy of... Jun 2024Cortical arealization arises during neurodevelopment from the confluence of molecular gradients representing patterned expression of morphogens and transcription...
Cortical arealization arises during neurodevelopment from the confluence of molecular gradients representing patterned expression of morphogens and transcription factors. However, whether similar gradients are maintained in the adult brain remains unknown. Here, we uncover three axes of topographic variation in gene expression in the adult human brain that specifically capture previously identified rostral-caudal, dorsal-ventral, and medial-lateral axes of early developmental patterning. The interaction of these spatiomolecular gradients i) accurately reconstructs the position of brain tissue samples, ii) delineates known functional territories, and iii) can model the topographical variation of diverse cortical features. The spatiomolecular gradients are distinct from canonical cortical axes differentiating the primary sensory cortex from the association cortex, but radiate in parallel with the axes traversed by local field potentials along the cortex. We replicate all three molecular gradients in three independent human datasets as well as two nonhuman primate datasets and find that each gradient shows a distinct developmental trajectory across the lifespan. The gradients are composed of several well-known transcription factors (e.g., and ), and a small set of genes shared across gradients are strongly enriched for multiple diseases. Together, these results provide insight into the developmental sculpting of functionally distinct brain regions, governed by three robust transcriptomic axes embedded within brain parenchyma.
Topics: Humans; Brain; Animals; Adult; Transcription Factors; PAX6 Transcription Factor; Gene Expression Regulation, Developmental; Male; Body Patterning; Female; Nerve Tissue Proteins
PubMed: 38861593
DOI: 10.1073/pnas.2219137121 -
Cureus May 2024An important goal in every lung resection is airtight closure of the resected lung surface. This can be achieved with several techniques, including clamp resection,...
INTRODUCTION
An important goal in every lung resection is airtight closure of the resected lung surface. This can be achieved with several techniques, including clamp resection, stapler, laser, and various high-frequency methods. By quantitatively measuring the air fistula across the resection surface of porcine lungs, two resection techniques were compared in our study: BipoJet dissecting scissors (Aesculap, Inc., Tuttlingen, Germany) and laser (Ceralas HPD®, Biolitec Inc., Jena, Germany).
METHODS
Following a stencil, wedge resections were performed in porcine lungs using water-irrigated bipolar scissors and laser (1350 nm, 40 watts, non-contact mode). The volume of the air fistula was then measured. The irrigation technique involved the attachment of an irrigation channel to a pair of standard surgical scissors. A sodium chloride (NaCl) solution was fed at a defined flow rate, along the blades of the scissors onto the parenchyma. This technique was used on a total of 10 specimens each.
RESULTS
Somewhat better pneumostasis was achieved with laser resection, though the difference was small and not statistically significant. The flow rate was 124 mL/min/cm² after laser resection and 145 mL/min/cm² after using the BipoJet scissors. The difference was not statistically significant. Water irrigation during resection with the BipoJet scissors prevents the temperature in the tissue from exceeding 100°C thus avoiding tissue carbonization. These scissors offer the following advantages: ease of use, no need to change instruments, no need for staff training, no protective measures, all-in-one incision/coagulation/dissection, low cost, and a clear surgical field due to the irrigation effect.
CONCLUSIONS
Resection of lung parenchyma, e.g., during resection of metastases, is easier with BipoJet scissors and comparable to laser resection. This was established both experimentally and by resecting lung metastases.
PubMed: 38860077
DOI: 10.7759/cureus.60088 -
Cureus May 2024This article highlights the case of a 37-year-old male who presented with a recurrent, exponentially enlarging head mass, emphasizing the diagnostic and therapeutic...
This article highlights the case of a 37-year-old male who presented with a recurrent, exponentially enlarging head mass, emphasizing the diagnostic and therapeutic challenges associated with a very rare type of tumor, fibrosarcomatous dermatofibrosarcoma protuberans (DFSP) of the head. Our patient presented with a rapidly growing head mass, initially diagnosed as a spindle cell tumor, and was managed with surgical excision and skin flap grafting. Follow-up revealed relapse and interval development of hemiparesis and hemisensory loss. MRI revealed tumor recurrence, with compression of the right parietal lobe and superior sagittal sinus. Histopathology revealed stroma with fascicles of spindle cells homogenous to fibrillar cytoplasm, with oval vesicular nuclei. Immunohistochemical staining showed positivity for CD34 and SMA. Oral chemotherapy with imatinib 800 mg/day was started. Follow-up imaging showed a marked reduction in the size of the tumor and resolution of the compression of the underlying brain parenchyma with cystic degeneration and decreased contrast enhancement. Future plans include possible surgical tumor debulking and/or radiation therapy. Although extremely rare, awareness of this tumor, with a multi-disciplinary approach to the management of the case, is vital to maximize treatment outcomes.
PubMed: 38860065
DOI: 10.7759/cureus.60110 -
Infectious Agents and Cancer Jun 2024A proportion of head and neck carcinomas (HNSCCs) are induced by high-risk human papillomaviruses (HPVs) and are associated with better patient outcomes compared to...
BACKGROUND
A proportion of head and neck carcinomas (HNSCCs) are induced by high-risk human papillomaviruses (HPVs) and are associated with better patient outcomes compared to patients with HNSCCs related to tobacco and alcohol abuse. In the microenvironment of solid tumors, including HNSCCs, oxygen levels are often reduced, and a hypoxic state is induced. This can lead to a poor treatment response and a worse patient prognosis. One of the hypoxia-responsive genes is aspartate-β-hydroxylase (ASPH), whose activity promotes the growth, invasiveness, and metastasis of many types of solid tumors.
METHODS
In our study, HNSCC samples were analyzed for the expression of ASPH and selected endogenous hypoxia markers by real-time PCR and/or multiplex fluorescence immunohistochemistry.
RESULTS
Except for the EPAS1 gene, which had higher mRNA expression in the HPV-negative group of HNSCC (p < 0.05), we found no other differences in the expression of the tested genes that were related to HPV status. On the contrary, a statistically significantly higher number of cells producing ASPH (p < 0.0001), HIF1A (p < 0.0001), GLUT1 (p < 0.0001), and MMP13 (p < 0.05) proteins were detected in the HPV-positive tumor group than in the HPV-negative sample group. All the evaluated markers, except for MMP9/13, were more abundant in the tumor parenchyma than in the tumor stroma. The Cox proportional hazard models showed that increased numbers of cells with GLUT1 and HIF1A protein expression were positive prognostic markers for overall and disease-specific survival in patients independent of HPV tumor status.
CONCLUSION
The study examined HNSCC samples and found that elevated ASPH and hypoxia marker proteins, typically associated with poor prognosis, may actually indicate active HPV infection, the strongest prognostic factor in HNSCC patients. In cases where HPV status is uncertain, increased expression of HIF1A and GLUT1 can serve as positive prognostic factors.
PubMed: 38858774
DOI: 10.1186/s13027-024-00588-1 -
Fluids and Barriers of the CNS Jun 2024Oedema occurs when higher than normal amounts of solutes and water accumulate in tissues. In brain parenchymal tissue, vasogenic oedema arises from changes in... (Review)
Review
Oedema occurs when higher than normal amounts of solutes and water accumulate in tissues. In brain parenchymal tissue, vasogenic oedema arises from changes in blood-brain barrier permeability, e.g. in peritumoral oedema. Cytotoxic oedema arises from excess accumulation of solutes within cells, e.g. ischaemic oedema following stroke. This type of oedema is initiated when blood flow in the affected core region falls sufficiently to deprive brain cells of the ATP needed to maintain ion gradients. As a consequence, there is: depolarization of neurons; neural uptake of Na and Cl and loss of K; neuronal swelling; astrocytic uptake of Na, K and anions; swelling of astrocytes; and reduction in ISF volume by fluid uptake into neurons and astrocytes. There is increased parenchymal solute content due to metabolic osmolyte production and solute influx from CSF and blood. The greatly increased [K] triggers spreading depolarizations into the surrounding penumbra increasing metabolic load leading to increased size of the ischaemic core. Water enters the parenchyma primarily from blood, some passing into astrocyte endfeet via AQP4. In the medium term, e.g. after three hours, NaCl permeability and swelling rate increase with partial opening of tight junctions between blood-brain barrier endothelial cells and opening of SUR1-TPRM4 channels. Swelling is then driven by a Donnan-like effect. Longer term, there is gross failure of the blood-brain barrier. Oedema resolution is slower than its formation. Fluids without colloid, e.g. infused mock CSF, can be reabsorbed across the blood-brain barrier by a Starling-like mechanism whereas infused serum with its colloids must be removed by even slower extravascular means. Large scale oedema can increase intracranial pressure (ICP) sufficiently to cause fatal brain herniation. The potentially lethal increase in ICP can be avoided by craniectomy or by aspiration of the osmotically active infarcted region. However, the only satisfactory treatment resulting in retention of function is restoration of blood flow, providing this can be achieved relatively quickly. One important objective of current research is to find treatments that increase the time during which reperfusion is successful. Questions still to be resolved are discussed.
Topics: Humans; Brain Edema; Animals; Brain; Blood-Brain Barrier; Brain Ischemia
PubMed: 38858667
DOI: 10.1186/s12987-024-00534-8 -
PloS One 2024Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the dysfunctional metabolism of carbohydrates, fats, and proteins caused by impaired insulin...
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the dysfunctional metabolism of carbohydrates, fats, and proteins caused by impaired insulin secretion and insulin resistance. This study investigated the feasibility of using point shear wave elastography (pSWE) of the pancreas by comparing the shear wave velocity (SWV) measurements of three anatomical areas in patients with T1DM and healthy volunteers. This study included 30 patients with T1DM (9 male, 21 female) and 23 healthy controls (11 men, 12 women). Two experienced certified operators performed the examinations and took the SWV measurements. The mean SWV of the entire pancreas parenchyma differed significantly between patients and controls (1.1 ± 0.29 and 0.74 ± 0.19 m/s, respectively; p ≤ 0.001). Moreover, the SWVs of the pancreatic segments were significantly different in patients and controls; the mean SWV values of the pancreas head, body, and tail (respectively) in patients vs. controls were 0.99 ± 0.36 vs. 0.76 ± 0.26 m/s (p = 0.012), 1.1 ± 0.52 vs. 0.74 ± 0.23 (p ≤ 0.001), and 1.0 ± 0.34 vs. 0.73 ± 0.28 (p ≤ 0.001). This study confirmed the feasibility of quantifying pancreas tissue stiffness with pSWE and revealed that patients with T1DM had higher pancreas tissue stiffness than controls. Further studies are required to determine the potential value of pSWE as a screening tool in patients with prediabetes.
Topics: Humans; Elasticity Imaging Techniques; Male; Female; Adult; Diabetes Mellitus, Type 1; Pancreas; Feasibility Studies; Middle Aged; Healthy Volunteers; Case-Control Studies
PubMed: 38857243
DOI: 10.1371/journal.pone.0303098 -
Annals of Indian Academy of Neurology May 2024Glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune inflammatory disorder affecting the central nervous system, involving the meninges, brain...
Glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune inflammatory disorder affecting the central nervous system, involving the meninges, brain parenchyma, and spinal cord. The distinctive radiologic feature observed on magnetic resonance imaging (MRI) is characterized by periventricular radial and linear contrast enhancement. This case report details a 45-year-old male who initially exhibited constitutional symptoms, followed by encephalitis, lower limb weakness, and urinary retention. The MRI findings revealed meningoencephalitis with longitudinal extensive myelitis. Notably, the cerebrospinal fluid analysis confirmed the presence of anti-GFAP antibodies.
PubMed: 38856160
DOI: 10.4103/aian.aian_1134_23 -
Exploration (Beijing, China) Apr 2024The glymphatic system plays a key role in the clearance of waste from the parenchyma, and its dysfunction has been associated with the pathogenesis of Alzheimer's...
The glymphatic system plays a key role in the clearance of waste from the parenchyma, and its dysfunction has been associated with the pathogenesis of Alzheimer's disease (AD). However, questions remain regarding its complete mechanisms. Here, we report that efflux of cerebrospinal fluid (CSF)/interstitial fluid (ISF) solutes occurs through a triphasic process that cannot be explained by the current model, but rather hints at the possibility of other, previously undiscovered routes from paravenous spaces to the blood. Using real-time, in vivo observation of efflux, a novel drainage pathway was discovered, in which CSF molecules enter the bloodstream directly through dynamically assembled, trumpet-shaped pores (basolateral <8 μm; apical < 2 μm) on the walls of brain venules. As Zn could facilitate the brain clearance of macromolecular ISF solutes, Zn-induced reconstruction of the tight junctions (TJs) in vascular endothelial cells may participate in pore formation. Thus, an updated model for glymphatic clearance of brain metabolites and potential regulation is postulated. In addition, deficient clearance of Aβ through these asymmetric venule pores was observed in AD model mice, supporting the notion that impaired brain drainage function contributes to Aβ accumulation and pathogenic dilation of the perivascular space in AD.
PubMed: 38855622
DOI: 10.1002/EXP.20230029 -
World Journal of Critical Care Medicine Jun 2024Mechanical ventilation (MV) is an important strategy for improving the survival of patients with respiratory failure. However, MV is associated with aggravation of lung...
Mechanical ventilation (MV) is an important strategy for improving the survival of patients with respiratory failure. However, MV is associated with aggravation of lung injury, with ventilator-induced lung injury (VILI) becoming a major concern. Thus, ventilation protection strategies have been developed to minimize complications from MV, with the goal of relieving excessive breathing workload, improving gas exchange, and minimizing VILI. By opting for lower tidal volumes, clinicians seek to strike a balance between providing adequate ventilation to support gas exchange and preventing overdistension of the alveoli, which can contribute to lung injury. Additionally, other factors play a role in optimizing lung protection during MV, including adequate positive end-expiratory pressure levels, to maintain alveolar recruitment and prevent atelectasis as well as careful consideration of plateau pressures to avoid excessive stress on the lung parenchyma.
PubMed: 38855266
DOI: 10.5492/wjccm.v13.i2.92441