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Long-acting fenofibrate-loaded microparticles for treating retinal disorders.

Age-related macular degeneration (AMD) and Diabetic retinopathy (DR) are the most common forms of retinal disorders and are the leading caus … VT dose of Feno-MP restored both photopic and scotopic electroretinogram (ERG) responses, decreased leukostasis, and enhanced blood-retinal barrier function over a period of 6 months. In Vldlr-/- mice, a wet-AMD model, Feno-MP effectively reduced both subretinal and intraretinal neovascularization and decreased retinal vascular leakage for at least 6 months. …

[Treatment in adult patients with acute myeloid leukemias and hyperleukocytosis at disease onset].

AIM: To evaluate the efficiency of the treatment policy for patients with acute myeloid leukemia (AML) and hyperleukocytosis (HL), which is … the disease. All the examinees received cytoreductive therapy with hydroxyurea and, in presence of leukostasis and/or leukocytosis (≥150-10(9)/1), with leukocytapheresis. In case of reduced leukocytosis, plasmapheresis was carried out to prevent (treat) cytolysis. Daunorubicin was injected on days 3-5 of the 7+3 induction cycle. RESULTS: The signs of leukos …

The pathogenesis of clostridial myonecrosis.

These pieces of evidence can be assimilated into a molecular and cellular model of pathogenesis which is initiated by direct toxin effects u … lting in marked localized edema. These events, combined with intravascular platelet aggregation and leukostasis, would increase venous pressures and favor further loss of fluid and protein in the distal capillary bed. Ultimately, a reduced arteriolar flow would impair oxygen delivery thereby attenuating phagocyte oxidative killing and facilitating anaerobic g …

Occult Neoplasms in Sudden Unexpected Death in Infancy: A Scoping Review of Post-Mortem Findings.

Background: Sudden unexpected death in infancy (SUDI) may occasionally be attributable to neoplasms that were clinically unrecognised before … uded arrhythmia, mechanical obstruction, respiratory failure, haemodynamic compromise, haemorrhage, leukostasis, and diffuse infiltration. Within the published cases included in this review, the review team classified the neoplasm as causal in 16 cases (16/32, 50.0%), contributory in 13 cases (13/32, 40.6%), and incidental in three cases (3/32, 9.4%). Conclus …

The Ins2Akita mouse as a model of early retinal complications in diabetes.

PURPOSE: This study tested the Ins2(Akita) mouse as an animal model of retinal complications in diabetes. The Ins2(Akita) mutation results i … o 36 weeks of hyperglycemia, the retinas were analyzed for vascular permeability, vascular lesions, leukostasis, morphologic changes of micro- and macroglia, apoptosis, retinal degeneration, and insulin receptor kinase activity. RESULTS: The mean blood glucose of Ins2(Akita) mice was significantly elevated, whereas the body weight at death was reduced compar …

[Chronic myeloid leukemia complicated with cerebellar hemorrhage and acute hydrocephalus successfully treated with imatinib and intensive supportive care].

We report a case of a 46-year-old female demonstrating general fatigue and visual disturbances with retinal bleeding. She had a white blood cell count of 419,300/mm. Thereafter, she developed vomiting associated with vertigo caused by cerebellar hemorrhage, deteriorating to acute hydrocephalus secondary to obstruction of the cerebral aqueduct. Emergency procedures for cerebral protection, such as hyperventilation, administration of mannitol, and barbiturate coma, were performed. Bone marrow examination showed a positive BCR-ABL/t(9;22)(q34;q11) chromosomal translocation detected by FISH and RT

Impact of Leukapheresis and Biological Risk Markers on Early Mortality in Patients with Hyperleukocytic Acute Myeloid Leukemia.

Background and Objectives: Hyperleukocytosis in acute myeloid leukemia (AML) is life-threatening, often complicated by leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulation (DIC), with very high early mortality. Leukapheresis (LA) can rapidly reduce circulating blast burden, but its effect on survival and prognostic relevance of disease markers remains unclear. Materials and Methods: We retrospectively analyzed 74 adult AML patients with WBC > 100 × 109/L treated at the University Clinical Center of Serbia between 2014 and 2024: 28 received LA plus cytoreduction (…

Microscopic acute lesions after caustic exposure.

Although lesions related to chemical burns have been studied through case reports, clinical analyses and autopsy series, microscopic lesions have not yet been precisely described. Our study analyses the microscopic lesions recorded after caustic exposure in fourteen lethal and four non-lethal cases. We find that microscopic lesions after caustic exposure are various and non-specific. Moreover, the distribution of gastrointestinal lesions is inconsistent. Histological changes affect the digestive mucosa first, with the entire wall suffering damage in some cases. Multiple factors influence the p

Ischaemia-induced retinal neovascularisation and diabetic retinopathy in mice with conditional knockout of hypoxia-inducible factor-1 in retinal Müller cells.

AIMS/HYPOTHESIS: Retinal Müller cells are known to produce inflammatory and angiogenic cytokines, which play important roles in diabetic retinopathy. Hypoxia-inducible factor (HIF)-1 has been shown to play a crucial role in retinal inflammation and neovascularisation. We sought to determine the role of Müller cell-derived HIF-1 in oxygen-induced retinopathy (OIR) and diabetic retinopathy using conditional Hif-1α (also known as Hif1a) knockout (KO) mice. METHODS: Conditional Hif-1α KO mice were generated by crossing mice expressing cyclisation recombinase (cre, also known as P1_gp003) in Mülle

Light-Sheet Microscopy of the Optic Nerve Reveals Axonal Degeneration and Microglial Activation in NMDA-Induced Retinal Injury.

PURPOSE: Optic nerve degeneration is a feature of neurodegenerative eye diseases and causes irreversible vision loss. Therefore, understandi … duces RGC and its axon loss, we confirmed that NMDA excitotoxicity induced microglia activation and leukostasis, such as increased microglia number, transform its morphology to ameboid or round, and increase in attached leukocytes in vessels. Using LSFM, we observed that CFP expressing nerve fiber was well organized and arranged parallel in vehicle treated op …

The cell in shock: the origin of multiple organ failure.

The immediate organ damage seen after multiple trauma and in shock is a typical example of non-bacterial inflammation triggered by activation of various mediators of both the humoral and cellular systems. Anaphylatoxins and the low-flow syndrome during the shock phase account for increased PMN* margination, which in turn causes pulmonary leukostasis and may provoke massive mediator release by PMN (oxygen radicals, proteinases, eicosanoids, PAF etc). This probably leads to severe endothelial cell damage, especially in the lung. Adherence of PMN to the endothelium appears to create the micro-env…

Angiogenesis and inflammation in the retinopathy risk of insulin and semaglutide - a review.

PURPOSE: To critically evaluate evidence supporting the angiogenesis-inflammation hypothesis in diabetic retinopathy (DR); to examine the ro … the blood-retinal barrier, while promoting endothelial adhesion molecule expression. The resulting leukostasis triggers hypoxia, leukocyte activation, and self-perpetuating ischemic-inflammatory loops. Insulin-like growth factor-1 further enhances retinal VEGF and angiopoietin-2 expression, potentially driving DR to the proliferative stage. Semaglutide, a gl …

Uncovering the potential mechanism and bioactive compounds of Salviae Miltiorrhizae Radix et Rhizoma in attenuating diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a serious microangiopathy resulting from diabetes. Salviae Miltiorrhizae Radix et Rhizoma (Danshen) … underlying mechanisms were predicted by network pharmacology and further validated by Western blot, leukostasis assay and real-time polymerase chain reaction (PCR). The primary active compounds in SWE were identified by integrating in vitro activity analysis and molecular docking. RESULTS: SWE attenuated BRB breakdown in STZ-induced DR mice. Results of netwo …

Superior protection in orthotopic rat lung transplantation with cyclic adenosine monophosphate and nitroglycerin-containing preservation solution.

BACKGROUND: Primary lung graft failure is common, and current lung preservation strategies are suboptimal. Because the decline in lung level … modynamic improvements provided by Columbia University solution were accompanied by decreased graft leukostasis and decreased recipient tumor necrosis factor alpha and interleukin 1alpha levels compared with the other groups. In toto, these improvements translated into superior survival among recipients of Columbia University solution-preserved grafts (100% f …

Neuroprotective Effects of HSF1 in Retinal Ischemia-Reperfusion Injury.

PURPOSE: Retinal ischemia, a common cause of several vision-threatening diseases, contributes to the death of retinal neurons, particularly retinal ganglion cells (RGCs). Heat shock transcription factor 1 (HSF1), a stress-responsive protein, has been shown to be important in response to cellular stress stimuli, including ischemia. This study is to investigate whether HSF1 has a role in retinal neuronal injury in a mouse model of retinal ischemia-reperfusion (IR). METHODS: IR was induced by inserting an infusion needle into the anterior chamber of the right eye and elevating a saline reservoir

Can hyperleukocytosis be caused by a non-hematologic condition? A 10-year retrospective tertiary-care center cohort study.

BACKGROUND: Hyperleukocytosis (HL) is defined as a white blood cell counts typically exceeding 100 G/L and is commonly associated with hematologic malignancies. Efforts to identify and characterize non-hematologic causes of HL have been limited and insufficiently addressed in the literature. METHODS: We conducted a retrospective analysis of adult patient records from 2013 to 2023, screened for cases of HL with a primary focus on the characterization of non-hematologic causes. RESULTS: Out of 878,967 adult patients, 375 patients had HL; 90 were excluded due to opting out of general consent, l

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… These disparities are explained by pathophysiological factors and the potential for leukostasis: While immature myeloid cells and monocytes have a high risk of causing leukostasis, small lymphocytes can reach much higher counts without producing clinical symptoms. … This aligns with a predominance of neutrophils, which are not typically associated with leukostasis. Paraneoplastic HL is driven by the overproduction of G-CSF and cytokines like interleukin-6 [ 15 ]. …

Acute Respiratory Failure in Patients with Hematologic and Solid Malignancies: Global Approach

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… Pulmonary Leukostasis Pulmonary leukostasis is an uncommon cause of severe hypoxemic respiratory failure in patients with acute leukemia who present with extremely high leukocyte or blast counts (>100,000/μL) and is associated with high mortality rates. … It manifests with severe hypoxemia and diffuse infiltrates secondary to leukostasis in the pulmonary vasculature and is associated with perivascular hemorrhage and interstitial edema. …

Multi-Omic Analysis Reveals the Impact of Bortezomib in Hyperleukocytic Acute Myeloid Leukemia.

BackgroundHyperleukocytic acute myeloid leukemia (HL-AML) is associated with early complications and high mortality rates, highlighting the urgent need for more effective therapeutic strategies.MethodsThis study conducted label-free proteomic analysis on serum from HL-AML and non-HL AML (NHL-AML) patients, integrating the data with the OHSU transcriptomic database. Flow cytometry was used to evaluate the in vitro impact of bortezomib. The in vivo effectiveness of bortezomib was assessed using the patient-derived xenograft (PDX) model of HL-AML.ResultsThrough integrated analysis of serum proteo

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… Cashen , “ Leukostasis in Adult Acute Hyperleukocytic Leukemia: A clinician's Digest ,” Hematological Oncology 34 ( 2016 ): 69 – 78 . 27018197 10.1002/hon.2292 6 R. M. Shallis , M. Stahl , J. P. Bewersdorf , J. E. Hendrickson , and A. M. … Rowe , “ Hyperleukocytosis, Leukostasis and Leukapheresis: Practice Management ,” Blood Reviews 26 ( 2012 ): 117 – 122 . 22364832 10.1016/j.blre.2012.01.003 8 P. Porcu , L. D. Cripe , E. W. …

Acute respiratory distress syndrome in patients with hematological malignancies: a one-year retrospective nationwide cohort study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) occurring in patients with hematological malignancies (HM) is a life-threatening condition with specific features. Mortality rate remains high but improvement has been described over the past several years. We aimed to describe characteristics and outcomes of ARDS in HM patients admitted in French ICUs (Intensive Care Units) during a one year-period. Data for this nationwide cohort study were collected from the French national hospital database (Programme de Médicalisation des Systèmes d'Information (PMSI)). All patients (18 years or older

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… leukostasis. Detailed codes for oncological characteristics are listed in appendix 2 . … Reversal of leukostasis-related pulmonary distress syndrome after leukapheresis and low-dose chemotherapy in acute myeloid leukemia. J Clin Oncol off J Am Soc Clin Oncol 10 sept. 2011;29(26):e725–726. 10.1200/JCO.2011.36.2756 10. Angirish B, Sanghavi P, Jankharia B. …