Extravasation Of Red Blood Cells Research Articles

PA24 Concomitant Crohn disease and scurvy: an unusual presentation revealing nutritional challenges

Abstract This case report presents a 15-year-old boy newly diagnosed with Crohn disease (CD), currently under treatment with prednisone and azathioprine. The patient was admitted to the hospital due to diffuse abdominal pain, diarrhoea and fever. Remarkably, after 5 days of hospitalization, he developed purpuric lesions on his wrists, abdomen and lower limbs. Dermoscopic examination of the cutaneous petechiae revealed an intriguing finding: whitish hair follicles exhibiting a distinctive ‘corkscrew’ hair pattern surrounded by a haemorrhagic violaceous halo. This dermoscopic profile strongly suggested the presence of scurvy. Histological analysis provided further insight, demonstrating perifollicular haemorrhage and interstitial extravasation of red blood cells. While nutritional deficiencies are commonly linked to CD, vitamin C deficiency is less frequently identified and reported, despite its prevalence. The challenge lies in the potential overlap of symptoms between active CD and scurvy, making the diagnosis of vitamin C deficiency more elusive in patients with CD. This case underscores the importance of considering vitamin C deficiency in the differential diagnosis of cutaneous manifestations in individuals with CD. Clinicians should be vigilant in identifying such nutritional deficiencies to ensure timely intervention and prevent complications associated with scurvy.

A Cross-Sectional Study of Epidemiological and Clinical Aspects of Pityriasis Rosea along with Dermoscopic Analysis and Histopathology Correlation.

Pityriasis Rosea (PR) is a common, yet enigmatic, dermatological condition characterized by a distinctive clinical presentation. Despite its prevalence, the aetiology and pathogenesis of PR remain elusive. To study the epidemiological and clinical aspects of patients with PR. To study dermoscopic findings and carry out histopathological correlation. A cross-sectional study of 50 patients was conducted. A detailed clinical history was taken and an examination was done followed by a dermoscopy. Quantitative data like age and duration of disease are presented with the help of standard deviation. Qualitative risk factors, like gender, age groups, symptomatology, site of lesion, findings or cutaneous examination, dermoscopy findings, and histopathology findings, are presented with the help of frequency and percentages. PR shows male preponderance and mean age of occurrence being 30.8 ± 15.7 years. Forty per cent of patients had an atypical clinical presentation. The most frequently seen dermoscopy findings were diffuse red background (58%), peripheral collarette scale (62%), and peripheral dotted vessels (50%). On histopathology, the most common findings were spongiosis (44%), parakeratosis (38%), irregular acanthosis (34%), perivascular lymphocytic infiltrate (56%), and red blood cell extravasation (36%). Sample size was less due to COVID. As this was a corss-sectional study follow up of patients could not be done. While the diagnosis of PR is clinical, it is difficult in atypical cases where dermoscopy comes to the aid. It also helps identify the age of lesions, thus helping decide the treatment strategy for patients. Biopsy remains the gold standard in ruling out other differentials of PR.

Therapeutic Approach in Pigmented Purpuric Dermatoses-A Scoping Review.

Pigmented purpuric dermatoses (PPD) encompass a group of chronic skin conditions characterized by the presence of petechiae, purpura, and pigmentation changes. While generally benign, these dermatoses can be persistent and aesthetically bothersome. Key clinical features include red to brownish patches with a distinctive "cayenne pepper" appearance, predominantly localized on the lower extremities, particularly the shins. Subtypes include Schamberg disease, Majocchi's disease, Gougerot-Blum disease, Ducas and Kapetanakis pigmented purpura, and lichen aureus. Diagnosis relies primarily on clinical evaluation of skin lesions, with biopsy as a confirmatory tool. Although the exact cause of PPD remains unclear, capillary fragility and red blood cell extravasation are implicated. Treatment strategies for PPD aim to alleviate symptoms, considering the generally benign and chronic nature of the condition. As there is no standardized treatment, various methods with varying efficacy are employed. After searching SCOPUS and PubMed databases, we assessed 42 original articles to present current knowledge regarding therapy of PPD. This review will compare treatment approaches specifically in Schamberg disease and other manifestations of pigmented purpuric dermatoses.

Ultrastructural insights from myocardial ablation lesions from microsecond pulsed field vs radiofrequency energy

BackgroundUltrastructural findings immediately after pulsed field ablation (PFA) of the myocardium have not been described. ObjectivesThe purpose of this study was to elucidate ultrastructural characteristics and differences between microsecond PFA at the 1- and 4-hour timepoints after pulse delivery and to compare them to irrigated radiofrequency ablation (RFA) lesions. MethodsHealthy swine underwent endocardial PFA or RFA followed by necropsy. Discrete microsecond PFA and irrigated RFA lesions were created in the ventricles with a lattice tip ablation catheter. Lesions were delivered in a manner so as to allow sampling to occur 1 and 4 hours after ablation. All lesions were located at necropsy, and samples were carefully obtained from within the lesion core, lesion periphery, and adjacent healthy myocardium. Transmission electron microscopic assessment was performed after fixation using paraformaldehyde and glutaraldehyde. ResultsOne hour after microsecond PFA delivery, myocytes were noted to be significantly and uniformly disrupted. Clustered, misaligned, swollen mitochondria coupled with degenerating nuclei and condensed chromatin were visualized. These findings progressed over the subsequent few hours with worsening edema. Similar changes were seen with RFA but reduced in severity. However, there was prominent extravasation of red blood cells with occlusion of capillaries that was not seen in PFA. At the lesion periphery, an abrupt change in the degree of myocyte damage was observed with PFA but not RFA. ConclusionTransmission electron microscopy demonstrates evidence of widespread destruction of myocytes as early as an hour after PFA and corroborates known histologic features such as sparing of vessels and sharp lesion margins.

The Connection between Chronic Liver Damage and Sporadic Alzheimer's Disease: Evidence and Insights from a Rat Model.

Junk foods are typically low in essential nutrients, such as vitamins, minerals, and antioxidants. They are also loaded with trans fats and saturated fats, which can increase the level of triglycerides in the blood. High triglyceride levels can contribute to the development of non-alcoholic fatty liver disease (NAFLD), a condition where excess fat accumulates in the liver. A high intake of junk foods can lead to insulin resistance, a condition where the body's cells become less responsive to insulin. A diet lacking in nutrients and loaded with unwanted toxins can impair the liver's ability to detoxify harmful substances and damage its overall function. It is known that the regular consumption of junk food can be linked to memory impairment and cognitive decline. Several studies have shown that diets high in unhealthy fats, sugars, and processed foods can negatively impact brain health, including memory function. In this study, Wistar rats were used to model Late-Onset Alzheimer's Disease (LOAD), which was inspired by knowledge of the liver-brain axis's role in causing dementia. The model mimicked junk-food-induced liver-brain damage, and was developed by using the toxins d-galactosamine, ethanol and d-galactose. To begin with, the model rats demonstrated insulin resistance, a characteristic of LOAD patients. Glucose levels in both the brain and liver tissues were significantly elevated in the model, paralleling clinical findings in LOAD patients. High glucose levels in the brain lead to the increased production of advanced glycation end-products (AGEs), which, along with amyloid beta, harm neighbouring neurons. Histopathological analysis revealed deformed glial nodules, apoptotic neurons, and amyloid plaques in the brain section in the later stages of the disease. Simultaneously, the liver section displayed features of cirrhosis, including an effaced lobular architecture and the extravasation of red blood cells. Liver enzymes ALT, AST and ALP were consistently elevated with disease progression. Furthermore, immunohistochemistry confirmed the presence of amyloid precursor protein (APP) in the diseased brain. The positive expression of Hypoxia-Inducible Factor 3-Alpha (HIF3A) in the brain indicated hypoxic conditions, which is consistent with other LOAD studies. This model also exhibited damaged intestinal villi and excessive bowel and urinary incontinence, indicating malnutrition and a disturbed gut microbiome, which is also consistent with LOAD patients. Bioinformatics analysis on serum protein suggests a few affected molecular pathways, like the amyloid secretase pathway, androgen/oestrogen/progesterone biosynthesis, the apoptosis signalling pathway, the insulin/IGF pathway-protein kinase B signalling cascade, the Metabotropic glutamate receptor group I pathway, the Wnt signalling pathway, etc. Behavioural analysis confirmed memory decline and the loss of muscle strength with disease progression. Overall, this rat model of LOAD sheds valuable light on LOAD pathology and highlights the potential link between liver dysfunction, particularly induced by the excessive consumption of junk food, and LOAD. This study contributes to a deeper understanding of the complex molecular mechanisms involved in LOAD, paving the way for new possibilities in therapeutic interventions.

Clinicopathological analysis of sclerosing angiomatoid nodular transformation in the spleen.

Splenic sclerosing angiomatoid nodular transformation (SANT) is a rare benign nodular lesion in the red medulla of the spleen. In the past, SANT has not been consistently recognized as the name for this condition and was often misdiagnosed for other conditions. In recent years, SANT has been acknowledged by most scholars as multiple reports have been published. To assess the clinicopathological features of SANT to identify the histological characteristics of SANT to improve diagnosis and clinical treatment. We assessed 25 cases of SANT diagnosed at Zhongshan Hospital affiliated with Fudan University from September 2014 to October 2021, including 14 men and 11 women, aged 24-62 years old. Fourteen cases were complicated with benign tumors of the liver, pancreas, kidney, uterus, and prostate. One case was complicated with renal clear cell carcinoma, and one was complicated with hepatocellular carcinoma. The gross neoplasm is multinodular and well defined. Histologically, angiomatoid nodules are composed of fattened, round, or irregular blood vessels, with or without red blood cells in the lumen, with unequal red blood cell extravasation, and fibrocytes around the nodules. The hemangiomatous nodules were positive for CD31 and CD34, while the vascular wall smooth muscle cells and fibrocytes around the nodules were positive for SMA. The diagnosis of SANT requires a combination of immunohistochemical and histological features, and early splenectomy is crucial for treatment.

Interdependence of Tissue Temperature, Cavitation, and Displacement Imaging During Focused Ultrasound Nerve Sonication.

Focused ultrasound (FUS) peripheral neuromodulation has been linked to nerve displacement caused by the acoustic radiation force; however, the roles of cavitation and temperature accumulation on nerve modulation are less clear, as are the relationships between these three mechanisms of action. Temperature directly changes tissue stiffness and viscosity. Viscoelastic properties have been shown to affect cavitation thresholds in both theoretical and ex vivo models, but the direct effect of temperature on cavitation has not been investigated in vivo. Here, cavitation and tissue displacement were simultaneously mapped in response to baseline tissue temperatures of either 30°C or 38°C during sciatic nerve sonication in mice. In each mouse, the sciatic nerve was repeatedly sonicated at 1.1 MHz, 4 MPa peak-negative pressure, 5 ms pulse duration, and either 15 Hz or 30 Hz pulse repetition frequency for 10 s at each tissue temperature. Cavitation increased by 1.8-4.5 dB at a tissue temperature of 38°C compared to 30°C, as measured both by passive cavitation images and cavitation doses. Tissue displacement also increased by 1.3-1.8 μm at baseline temperatures of 38°C compared to 30°C. Histological findings indicated small increases in red blood cell extravasation in the 38°C baseline temperature condition compared to 30°C at both PRFs. A strong positive correlation was found between the inertial cavitation dose and displacement imaging noise, indicating the potential ability of displacement imaging to simultaneously detect inertial cavitation in vivo. Overall, tissue temperature was found to modulate both in vivo cavitation and tissue displacement, and thus both tissue temperature and cavitation can be monitored during FUS to ensure both safety and efficiency.

Hyperpigmentation after sclerotherapy: modern possibilities for prevention and treatment

Sclerotherapy is one of the most popular and most common techniques for the removal of delated reticular veins and telangiectasias on the lower limbs. Despite the vast pooled experience, this procedure can be accompanied by a number of undesirable side effects, of which post-injection hyperpigmentation, which frequency reaches 80%, is the most unpleasant one. The development of postsclerotherapy hyperpigmentation (PSHP) is associated with extravasation and destruction of red blood cells, which results in transformation of haemoglobin into hemosiderin pigment. PSHP is, by definition, a variant of post-traumatic hemosiderin pigmentation. The likelihood of occurrence and persistence of PSHP is determined by a number of hard controllable factors, including the calibre and location of the target veins, the type, concentration and physical form of the sclerosing agent, the sclerotherapy technique, the method and duration of post-procedural compression, patients’ ethnicity, iron metabolism disorders, concomitant use of a number of drugs, a menstrual cycle phase in women, etc. Hyperpigmentation significantly decreases the patients’ quality of life, which determines the need for the prevention and treatment of this undesirable side effect of phlebosclerosing treatment. Recommendations for prevention of PSHP include a detailed history taking aimed at identifying potential risk factors, in the presence of which it is advisable to use various systemic and topical drugs in the post-procedural period in order to prevent the skin hemosiderin deposition, as well as to apply the extended-cycle compression. In the case of PSHP, procedures aimed at the destruction and utilization of hemosiderin, such as Q-Switched laser and IPL therapy, as well as various peeling options intended to speed up the replacement of pigmented skin with normal, can be applied. For the PSHP prevention and treatment, the use of Contractubex containing cepalin onion extract in combination with allantoin and heparin is a matter of interest. Contractubex is a drug originally intended to optimize wound healing and prevent the formation of hypertrophic scars. At the same time, there is ample publications discussing the possible use of this drug for the management of post-traumatic hyperpigmentation due to the combined action of its components. Our clinical experience confirms the effectiveness of Contractubex in the treatment of PSHP, which determines the feasibility of conducting full-fledged clinical trials and accumulating more pooled experience in this area.

SGLT2 inhibitor dapagliflozin alleviates intramyocardial hemorrhage and adverse ventricular remodeling via suppressing hepcidin in myocardial ischemia-reperfusion injury

Intramyocardial hemorrhage (IMH), a reperfusion therapy-associated complication, is the extravasation of red blood cells caused by severe microvascular injury. IMH is an independent predictor of adverse ventricular remodeling (AVR) after acute myocardial infarction (AMI). Hepcidin, a major regulator of iron uptake and systemic distribution, is a key factor affecting AVR. However, the role of cardiac hepcidin in the development of IMH has not been completely elucidated. This study aimed to explore if sodium-dependent glucose co-transporter 2 inhibitor (SGLT2i) exerts therapeutic effects on IMH and AVR by suppressing hepcidin and to elucidate the underlying mechanisms. SGLT2i alleviated IMH and AVR in the ischemia-reperfusion injury (IRI) mouse model. Additionally, SGLT2i downregulated the cardiac levels of hepcidin in IRI mice, suppressed M1-type macrophage polarization, and promoted M2-type macrophage polarization. The effects of hepcidin knockdown on macrophage polarization were similar to those of SGLT2i in RAW264.7 cells. SGLT2i treatment or hepcidin knockdown inhibited the expression of MMP9, an inducer of IMH and AVR, in RAW264.7 cells. Regulation of macrophage polarization and reduction of MMP9 expression by SGLT2i and hepcidin knockdown is achieved through activation of pSTAT3. In conclusion, this study demonstrated that SGLT2i alleviated IMH and AVR by regulating macrophage polarization. The potential mechanism through which SGLT2i exerted its therapeutic effect seems to involve the downregulation of MMP9 via the hepcidin-STAT3 pathway.

Enhanced Vulnerability of Diabetic Mice to Hypervirulent Streptococcus agalactiae ST-17 Infection.

Streptococcus agalactiae (Group B Streptococcus, GBS) is the leading cause of neonatal sepsis and meningitis but has been recently isolated from non-pregnant adults with underlying medical conditions like diabetes. Despite diabetes being a key risk factor for invasive disease, the pathological consequences during GBS infection remain poorly characterized. Here, we demonstrate the pathogenicity of the GBS90356-ST17 and COH1-ST17 strains in streptozotocin-induced diabetic mice. We show that GBS can spread through the bloodstream and colonize several tissues, presenting a higher bacterial count in diabetic-infected mice when compared to non-diabetic-infected mice. Histological sections of the lungs showed inflammatory cell infiltration, collapsed septa, and red blood cell extravasation in the diabetic-infected group. A significant increase in collagen deposition and elastic fibers were also observed in the lungs. Moreover, the diabetic group presented red blood cells that adhered to the valve wall and disorganized cardiac muscle fibers. An increased expression of KC protein, IL-1β, genes encoding immune cell markers, and ROS (reactive oxygen species) production was observed in diabetic-infected mice, suggesting GBS promotes high levels of inflammation when compared to non-diabetic animals. Our data indicate that efforts to reverse the epidemic of diabetes could considerably reduce the incidence of invasive infection, morbidity and mortality due to GBS.

Imaging and Histopathological Analysis of Microvascular Angiogenesis in Photodynamic Therapy for Oral Cancer.

The objective of this study is to use imaging and histopathological analysis to characterize and monitor microvascular responses to photodynamic therapy (PDT). In vivo chicken chorioallantoic membranes (CAMs) and a stimulated malignant oral lesions animal model were used to determine the blood flow and the biological activities of Photofrin® (2.5 mg/kg) exposed to different laser power densities at 630 nm. The vascular changes, the velocity of the blood flow, the speckle flow index (SFI) of fluorescence changes, and ultrastructure damage in the microvasculature before and after PDT were recorded. The subcellular localization of Photofrin® revealed satisfactory uptake throughout the cytoplasm of human red blood cells at 10 s and 20 s before PDT. The mean blood-flow velocities of the veins and arteries were 500 ± 40 and 1500 ± 100 μm/s, respectively. A significant decrease in the velocities of the blood flow in the veins and arteries was detected in the CAM model after PDT. The veins and arteries of CAMs, exposed to the power densities of 80, 100, and 120 mW/cm2, had average blood-flow velocities of 100 ± 20, 60 ± 10, and 0 μm/s and 300 ± 50, 150 ± 30, and 0 μm/s, respectively. In the stimulated malignant oral lesions animal model, the treated tumors exhibited hemorrhage and red blood cell extravasation after PDT. The oxyhemoglobin and total hemoglobin levels decreased, which resulted in a decrease in tissue oxygen saturation, while the deoxyhemoglobin levels increased. PDT using Photofrin® has the ability to cause the destruction of the targeted microvasculature under nonthermal mechanisms selectively.

Utility of Dermoscopy in Cutaneous Small Vessel Vasculitis: Preliminary Observations from a Study of 30 Cases.

Dermoscopy is a non-invasive diagnostic technique that provides an added advantage to the routine clinical diagnostic exercise. Role of dermoscopy in cutaneous small vessel vasculitis has not been explored well. This study was intended to delineate the dermoscopic features of cutaneous small vessel vasculitis and to correlate them with histopathological findings of the disease. This was a cross-sectional study involving 30 patients with cutaneous small vessel vasculitis confirmed by histopathology and direct immunofluorescence. In each patient, dermoscopic features of early/evolving and established lesions were recorded. Dermoscopic-histopathological correlation was assessed for established lesions. On dermoscopy, the early/evolving lesions showed a dull red background in all the 30 (100%) patients, red globules in 8 (26.7%), and red dots in 4 (13.30%) patients. The established lesions showed red background in 28 (93.3%) patients, white and yellow structureless areas in 19 (63.33%) patients each, red globules in 18 (60%), and red dots in 16 (53.3%) patients. A statistically significant association between red globules and red blood cell extravasation was noted (P-0.01). White and yellow structureless areas also showed a statistically significant association between sparse (P-0.023) and dense (P-0.007) perivascular infiltrates, respectively. Dermoscopy of cutaneous small vessel vasculitis exhibits fairly reliable and reproducible features correlating well with histopathological aspects of the disease. Hence, inclusion of dermoscopy in the clinical diagnostic protocol for cutaneous small vessel vasculitis is beneficial in complementing the clinical diagnosis and in differentiating from other inflammatory purpuras.

Cavitation Feedback Control of Focused Ultrasound Blood-Brain Barrier Opening for Drug Delivery in Patients with Parkinson's Disease.

Magnetic resonance-guided focused ultrasound (MRgFUS), in conjunction with circulating microbubbles, is an emerging technology that can transiently enhance the permeability of the blood-brain barrier (BBB) locally and non-invasively to facilitate targeted drug delivery to the brain. In this clinical trial, the feasibility and safety of BBB modulation in the putamen were evaluated for biweekly therapeutic agent delivery in patients with Parkinson's disease. The performance of the clinical MRgFUS system's cavitation feedback controller for active power modulation throughout the exposures was examined. The putamen was targeted unilaterally by an ExAblate Neuro MRgFUS system operating at 220 kHz. Definity microbubbles were infused via a saline bag gravity drip at a rate of 4 µL/kg per 5 min. A cavitation emissions-based feedback controller was employed to modulate the acoustic power automatically according to prescribed target cavitation dose levels. BBB opening was measured by Gadolinium (Gd)-enhanced T1-weighted MR imaging, and the presence of potential micro-hemorrhages induced by the exposures was assessed via T2*-weighted MR imaging. A total of 12 treatment sessions were carried out across four patients, with target cavitation dose levels ranging from 0.20-0.40. BBB permeability in the targeted putamen was elevated successfully in all treatments, with a 14% ± 6% mean increase in Gd-enhanced T1-weighted MRI signal intensity relative to the untreated contralateral side. No indications of red blood cell extravasations were observed on MR imaging scans acquired one day following each treatment session. The cavitation emissions-based feedback controller was effective in modulating acoustic power levels to ensure BBB permeability enhancement while avoiding micro-hemorrhages, however, further technical advancements are warranted to improve its performance for use across a wide variety of brain diseases.

PSUN62 A Rare Case of Atorvastatin Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome - A Case Report.

Abstract Clinical Case A 77 year-old female presented to emergency department with progressively worsening rash that started one week ago. On physical examination blanching erythema was noted in lower back, buttocks and extremities. There was no desquamation or involvement of oral mucosa. No lymphadenopathy or hepatosplenomegaly was noted. Laboratory investigations showed white blood cell count of 21.2×10^3/uL, with 33.1% eosinophils. Creatinine was elevated at 2.8mg/dL from baseline of 0.8mg/dL. Further lab work revealed alkaline phosphate 2314 IU/L, aspartate transaminase 587 IU/L, and alanine transaminase 620 U/L, total bilirubin 7.3mg/dL with direct bilirubin of 5.1mg/dL, Immunoglobulin E level of 2000 IU/ml and normal Tryptase levels. Serology for viral hepatitis, Epstein-Barr virus, Cytomegalovirus and Human immunodeficiency virus was negative. Autoimmune workup including antinuclear Antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), mitochondrial antibody, smooth muscle antibody, double stranded DNA, anti-histone antibody, rheumatoid factor, Sjogren's antibody and centromere antibody were negative. Urinalysis, urine protein electrophoresis and serum protein electrophoresis were also normal. Computed tomography (CT) scan of chest showed mild supraclavicular and mediastinal lymphadenopathy. Review of medical records revealed that patient was recently discharged from hospital with a prescription of Atorvastatin following admission for transient ischemic attack 6 weeks ago. Skin biopsy showed superficial perivascular dermatitis with extravasation of red blood cells with no diagnostic evidence of vasculitis, granuloma or malignancy. Based on biopsy findings, recent drug administration followed by appearance of rash, hematological abnormality, lymphadenopathy and multi-system involvement and after exclusion of other possible causes, diagnosis of DRESS syndrome was made. Atorvastatin was held and patient was given Methylprednisolone for three days followed by Prednisone 1mg/kg with taper. Rash as well as kidney and liver functions improved drastically within two days. Discussion Our patient presented with one week of rash associated with deteriorating kidney and liver functions. Atorvastatin was initiated five weeks prior to development of rash. All the possible infectious etiologies and malignancy was ruled out based on the laboratory work mentioned above. Work up for vasculitis was also negative. DRESS syndrome is a late onset drug induced hypersensitivity reaction which usually manifests 3 weeks to months after the offending drug is started. It is very rare with an incidence of 0.9-2 per 100,000 patients per year and accounts for 10-20% of all cutaneous adverse drug reactions. DRESS syndrome if untreated carries significant risk of mortality, between 10-20%. RegiSCAR (European Registry of Severe Cutaneous Adverse Reaction) scoring system can be used to help diagnose DRESS syndrome. It takes into account multiple factors including fever, lymphadenopathy, eosinophilia, rash, number of organs involved, disease duration, skin biopsy findings and negative results of investigations to rule out alternate causes of patient's symptoms. Patient responded well to systemic steroids followed by oral steroids with taper. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Rapidly progressing dyspnea and retiform purpura

Rapidly progressing dyspnea and retiform purpura

High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection.

Low-intensity transcranial focused ultrasound (FUS) has gained momentum as a non-/minimally-invasive modality that facilitates the delivery of various pharmaceutical agents to the brain. With the additional ability to modulate regional brain tissue excitability, FUS is anticipated to confer potential neurotherapeutic applications whereby a deeper insight of its safety is warranted. We investigated the effects of FUS applied to the rat brain (Sprague-Dawley) shortly after an intracortical injection of fluorescent interstitial solutes, a widely used convection-enhanced delivery technique that directly (i.e., bypassing the blood–brain-barrier (BBB)) introduces drugs or interstitial tracers to the brain parenchyma. Texas Red ovalbumin (OA) and fluorescein isothiocyanate-dextran (FITC-d) were used as the interstitial tracers. Rats that did not receive sonication showed an expected interstitial distribution of OA and FITC-d around the injection site, with a wider volume distribution of OA (21.8 ± 4.0 µL) compared to that of FITC-d (7.8 ± 2.7 µL). Remarkably, nearly half of the rats exposed to the FUS developed intracerebral hemorrhaging (ICH), with a significantly higher volume of bleeding compared to a minor red blood cell extravasation from the animals that were not exposed to sonication. This finding suggests that the local cerebrovascular injury inflicted by the micro-injection was further exacerbated by the application of sonication, particularly during the acute stage of injury. Smaller tracer volume distributions and weaker fluorescent intensities, compared to the unsonicated animals, were observed for the sonicated rats that did not manifest hemorrhaging, which may indicate an enhanced degree of clearance of the injected tracers. Our results call for careful safety precautions when ultrasound sonication is desired among groups under elevated risks associated with a weakened or damaged vascular integrity.

Diffuse Alveolar Hemorrhage as an Unusual Pulmonary Manifestation of Multisystem Inflammatory Syndrome in Adults

Multisystem inflammatory syndrome–A (MIS-A) is a rare postacute complication of COVID-19 infection in adults. It is a hyperinflammatory condition presenting as cardiogenic and vasogenic shock leading to multiorgan failure. Diffuse alveolar hemorrhage (DAH) is a rare pulmonary condition, with diverse etiologies ultimately leading to the extravasation of red blood cells into alveoli, resulting in respiratory compromise. The association between MIS-A and DAH has not been reported in the literature. Here, we describe a case of a 33-year-old man who presents with shock and diffuse alveolar hemorrhage in the setting of a highly inflammatory state, consistent with MIS-A.

ORAL HIV-ASSOCIATED KAPOSI'S SARCOMA WITH ATYPICAL CLINICAL PRESENTATION: REPORT OF A CASE

Kaposi's sarcoma is a multifocal angioproliferative malignant neoplasm caused by human herpesvirus 8 (HHV-8) and commonly associated with acquired immunodeficiency syndrome (AIDS). A 25-year-old male patient recently diagnosed with AIDS was referred for consultation reporting multiple intraoral lesions with 2 months of evolution. Physical examination revealed diffuse multinodular purplish-red lesions of fibroelastic consistency, associated with spontaneous bleeding, affecting the whole maxillary and mandibular keratinized mucosa. Incisional biopsy was performed. Histopathologic examination revealed a mucosal fragment covered by stratified squamous epithelium exhibiting a large amount of blood vessels in the connective tissue and vascular proliferation associated with a large number of spindle-shaped neoplastic cells and red blood cell extravasation. Immunohistochemistry for HHV-8 was positive, confirming the diagnosis of Kaposi's sarcoma. After 3 months of systemic chemotherapy with liposomal doxorubicin the patient showed improvement of the oral lesions.

LB876 Acute inflammatory edema: A challenging diagnosis in a critically ill patient

A 55-year-old man with a prior history of fibrotic lung disease was admitted to the hospital for bilateral lung transplantation. His post-operational course was complicated by severe volume overload requiring initiation of continuous veno-venous hemodialysis (CVVHD). During this hospitalization, he had developed erythematous plaques over his bilateral thighs. Examination revealed erythematous and edematous plaques with a peau d’orange appearance extending over his bilateral thighs and abdominal pannus. Importantly, the inguinal and infra-abdominal folds were spared. The clinical differential diagnosis included acute inflammatory edema (AIE), early lipodermatosclerosis (LDS), and stasis change. Punch biopsy of a thigh lesion revealed prominent dermal edema, a sparse perivascular and interstitial lymphohistiocytic infiltrate, ectactic vessels, and fibrosis: findings consistent with a diagnosis of AIE. Improvement of the patient’s volume status, increased mobility, and frequent position changes were recommended. AIE is a variant of pseudocellulitis characterized by erythematous and edematous plaques primarily found on the thighs and abdomen that spare areas of increased pressure, such as the inguinal folds. AIE is an acute lymphedema that predominantly affects critically ill patients with hypoalbuminemia, increased body mass index, renal impairment, and evidence of fluid overload. LDS and stasis dermatitis can also present on the thighs and pannus; however, these conditions also commonly manifest on the distal lower extremities and do not spare skin folds. Additionally, LDS and stasis are typically chronic rather than acute. LDS is a lobular panniculitis with fat necrosis, lipomembranous change, and septal fibrosis. In stasis, there are an increased number of thickened capillaries, red blood cell extravasation, and siderophages.

A new mouse model of radiation-induced liver disease reveals mitochondrial dysfunction as an underlying fibrotic stimulus

Background & AimsHigh-dose irradiation is an essential tool to help control the growth of hepatic tumors, but it can cause radiation-induced liver disease (RILD). This life-threatening complication manifests itself months following radiation therapy and is characterized by fibrosis of the pericentral sinusoids. In this study, we aimed to establish a mouse model of RILD to investigate the underlying mechanism of radiation-induced liver fibrosis.MethodsUsing a small animal image-guided radiation therapy platform, an irradiation scheme delivering 50 Gy as a single dose to a focal point in mouse livers was designed. Tissues were analyzed 1 and 6 days, and 6 and 20 weeks post-irradiation. Irradiated livers were assessed by histology, immunohistochemistry, imaging mass cytometry and RNA sequencing. Mitochondrial function was assessed using high-resolution respirometry.ResultsAt 6 and 20 weeks post-irradiation, pericentral fibrosis was visible in highly irradiated areas together with immune cell infiltration and extravasation of red blood cells. RNA sequencing analysis showed gene signatures associated with acute DNA damage, p53 activation, senescence and its associated secretory phenotype and fibrosis. Moreover, gene profiles of mitochondrial damage and an increase in mitochondrial DNA heteroplasmy were detected. Respirometry measurements of hepatocytes in vitro confirmed irradiation-induced mitochondrial dysfunction. Finally, the highly irradiated fibrotic areas showed markers of reactive oxygen species such as decreased glutathione and increased lipid peroxides and a senescence-like phenotype.ConclusionsBased on our mouse model of RILD, we propose that irradiation-induced mitochondrial DNA instability contributes to the development of fibrosis via the generation of excessive reactive oxygen species, p53 pathway activation and a senescence-like phenotype.Lay summaryIrradiation is an efficient cancer therapy, however, its applicability to the liver is limited by life-threatening radiation-induced hepatic fibrosis. We have developed a new mouse model of radiation-induced liver fibrosis, that recapitulates the human disease. Our model highlights the role of mitochondrial DNA instability in the development of irradiation-induced liver fibrosis. This new model and subsequent findings will help increase our understanding of the hepatic reaction to irradiation and to find strategies that protect the liver, enabling the expanded use of radiotherapy to treat hepatic tumors.