Diffuse Edema Research Articles

Preliminary evidence that Bunyamwera virus causes severe disease characterized by systemic vascular and multiorgan necrosis in an immunocompromised mouse model.

Bunyamwera virus (BUNV) is the prototypical member of the Bunyamwera serogroup within the Orthobunyvirus genus. BUNV is transmitted by mosquito vectors of the genera Culex, Aedes and Anopheles and has historically circulated in East Africa, though the transmission has been observed in Argentina. BUNV has been identified as an agent of human and animal disease and has also been misdiagnosed as other agents. BUNV is often thought to be an agent of mild febrile illness in humans, though it can cause abortions in ruminants and neurological disease in horses. Joint pain and gastritis have also been attributed to BUNV. There are limited data concerning the possible spectrum of disease and extent of pathogenesis of BUNV infection, and there are currently no therapeutics or vaccines available. Furthermore, options for animal models for Orthobunyaviruses in general - of which BUNV is the prototypical member - are limited. Eight mice deficient in the type I interferon response were infected with BUNV, and all developed overt disease. All mice developed detectable viraemia and clinical signs, including weight loss, hunched posture and lethargy. Three of the eight mice developed severe diseases, including vascular necrosis and necrosis in the liver, lungs, reproductive organs, bone marrow and spleen, as well as haemorrhages (n=1) and severe diffuse facial oedema (n=3), reminiscent of the pathology of Schmallenberg and the Arenaviruses Lassa and Lujo viruses. Thus, BUNV infection of IRF3/7 DKO mice could serve as a BSL-2 model for severe diseases of higher-risk group viruses, which often must be studied at BSL-4. Additionally, our results suggest that BUNV may have the ability to cause severe disease in immunocompromised hosts. Thus, further investigation into the potential spectrum of pathogenesis due to BUNV is important to prioritize for outbreak response, diagnostics and the development of countermeasures.

P49 Belimumab as a potential therapy for lupus enteritis – a case report

Abstract Introduction Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with varied clinical manifestations. Gastrointestinal (GI) complaints are common in 40–60% of SLE patients. Most are mild; however severe life-threatening manifestations may occur. Lupus enteritis (LE) is a rare but severe GI manifestation of SLE, characterised by vasculitis or inflammation of the bowel. Belimumab is a recombinant human monoclonal antibody against the soluble B-lymphocyte stimulator protein (BLyS) and was the first licensed treatment for SLE and lupus nephritis. Herein, we report a case of lupus enteritis that responded well to belimumab therapy. Case description We present a 42-year-old Sri Lankan woman who was diagnosed with SLE in 2015 based on arthritis, Raynaud’s, haemoproteinuria, positive antinuclear antibodies (ANA), anti-double stranded DNA (dsDNA), and anti-Ro antibodies with low complements C3, C4. Renal biopsy confirmed class III a+c lupus nephritis. She was managed with prednisolone, mycophenolate mofetil, hydroxychloroquine and ramipril. She responded well to treatment. She was admitted in August 2018 with recurrent abdominal pains, distension, diarrhoea, nausea, vomiting, 20kg unintentional weight loss, arthritis, lymphadenopathy, and peripheral oedema. Over the last 12 months, she had 5 admissions with similar GI symptoms, which were managed as viral gastroenteritis. Investigations showed nephrotic range proteinuria - urine PCR 330 (0-15 mg/mmol), low albumin = 27 (40-52 g/L), positive anti-dsDNA antibodies = 211 (0-10 IU/ml), CRP 7 (0-4 mg/L), ESR 44 (0-12 mm/hr) with low complements C3 0.36 (0.90-1.80 g/L) and C4 0.07 (0.10-0.40 g/L). Contrast enhanced computed tomography (CECT) scan of the abdomen revealed diffuse oedema of the large bowel extending from the splenic flexure to the rectum, several areas of small bowel thickening, peritoneal enhancement, and moderate volume ascites. Infective causes for colitis were ruled out including abdominal tuberculosis. Sigmoidoscopy and biopsy ruled out inflammatory bowel disease, whereas surgical and gastroenterology reviews ruled out other causes for her presentation. She was diagnosed with lupus enteritis with flare of lupus nephritis and managed with pulsed intravenous methylprednisolone followed by tapering high dose oral prednisolone. Her symptoms gradually improved, and she was discharged. Unfortunately, over the next month, she had recurrent admissions with flares of lupus enteritis requiring further intravenous methylprednisolone. As a result, she was commenced on monthly IV belimumab. Since starting belimumab, she has not had any further flares of lupus enteritis and her anti-dsDNA antibody and complements C3, C4 levels have normalised. Discussion Lupus enteritis (LE) presents with non-specific GI symptoms such as abdominal pain (most common), nausea, vomiting, diarrhoea and ascites. In most cases, it develops months to years after SLE diagnosis but in some cases, may be the presenting feature. Its pathogenesis remains unknown; however, mesenteric vasculitis and/or thromboses are thought to play a role. Contrast enhanced computed tomography (CECT) abdomen is the gold-standard investigation and usually shows bowel wall oedema, dilated bowel loops (>3 cm), bowel wall thickening with peripheral enhancement (“target sign”/”double halo sign”), engorgement of mesenteric vessels with a palisade pattern (“comb-sign”), increased attenuation of mesenteric fat and/or ascites. Laboratory investigations usually reveal markers of active lupus. Significant proteinuria (>0.5 g/24 h) is usually found in around 50% of patients. LE is very steroid responsive, with most patients achieving disease remission with steroids alone. Additional immunosuppression (such as cyclophosphamide, MMF, azathioprine, HCQ or rituximab) may be used concomitantly, for other manifestations of SLE or in those with relapsing or refractory disease. Belimumab has previously been licensed for use in SLE and lupus nephritis; however, there is sparse literature about its use in lupus enteritis. Our patient responded very well to belimumab, with both clinical and immunological remission. Key learning points • Lupus enteritis is a rare but severe gastrointestinal (GI) manifestation of SLE that presents with non-specific GI symptoms such as abdominal pain (most common), nausea, vomiting, diarrhoea and ascites. Clinicians managing SLE patients should have a high index of suspicion regarding the diagnosis, else it may be easily missed leading to recurrent admissions and delayed treatment. • Contrast enhanced CT abdomen is the gold-standard investigation and shows characteristic changes - bowel wall oedema, dilated bowel loops (>3 cm), bowel wall thickening with peripheral enhancement (“target sign”/”double halo sign”), engorgement of mesenteric vessels with a palisade pattern (“comb-sign”), increased attenuation of mesenteric fat and/or ascites • Lupus enteritis is very steroid responsive, with most patients achieving disease remission with steroids alone. Some patients with other SLE manifestations, or relapsing/refractory disease may require additional immunosuppression. Belimumab may be another option to consider in such patients.

Combined PVI and LAAC is feasible using RFA or PFA in a canine model despite acute tissue edema in PFA versus RFA

Abstract Background Combined procedure with pulmonary vein isolation (PVI) using thermal energy followed by left atrial appendage closure (LAAC) has been used in select patient populations with positive results. Pulsed field ablation (PFA) is a novel non-thermal ablation modality that ablates cardiac tissue by irreversible electroporation. The effect of PFA on cardiac tissue and its interaction with a LAAC device in a single procedure has not been studied. Purpose To evaluate using transesophageal echo (TEE) imaging the acute tissue response following ablation by PFA compared to radiofrequency ablation (RFA) and its interaction with the WATCHMAN FLX Pro LAAC device when used in a combined procedure in a healthy canine model. Methods Nine mongrel canines underwent PVI using either circumferential PFA (FARAPULSE) energy application (n=6) or RFA energy (n=3). TEE imaging was obtained at the time of the procedure before and immediately after ablation energy application. The general appearance and echogenicity of the left lateral ridge was assessed and the os of the left atrial appendage (LAA) was measured in the four standard TEE views (0, 45, 90, and 135 degrees). Decisions about device sizing were made accordingly. PVI was evaluated by entry and exit block in all veins except the right inferior pulmonary vein (RIPV), which was not ablated. Following ablation, the LAAC device was implanted using TEE and fluoroscopic guidance in all animals and the percentage of compression measured. PASS criteria were assessed before the release of each device. All animals received dual antiplatelet therapy post implant. Results PVI was confirmed in all animals (except RIPV which was not targeted for ablation) using PFA and RFA. LAA dimensions (at device landing site) did not change substantially after RF ablation. With PFA, there was evidence of more diffuse edema and decrease in LAA diameter (Table). The LAAC device was implanted successfully after meeting PASS criteria in all animals within 30 minutes post ablation. The device size was decreased following PFA in two (2/6) animals, whereas there was no deviation from baseline measurements in device size for any of the RFA animals. Average LAAC device compression was higher for PFA versus RFA animals (Table). TEE post implant confirmed absence of any peri-device leaks in all animals. Conclusion Concomitant PVI using PFA (FARAPULSE) and LAAC (WATCHMAN FLX Pro) is feasible with 100% success and no residual acute peri-device leak. In the canine model, PFA is associated with more diffuse edema compared to RFA, which might affect device sizing. Long term consequences of this acute edema need to be evaluated in serial imaging and future larger clinical trials.Table

Acute necrotizing encephalopathy caused by bacterial infection

PurposeAcute necrotizing encephalopathy (ANE), a rare and severe brain disorder, is typically linked to prior infections. ANE predominantly affects children, with most reported cases attributed to viral infections. However, instances of bacterial-induced ANE are infrequent. Here, we present a case of adult-onset ANE associated with bacterial infection.Case descriptionsThe patient exhibited a hyperinflammatory state following a urinary tract bacterial infection, with neurological function rapidly declining into a coma as the illness progressed. Gram culture of blood suggested Escherichia coli infection. A magnetic resonance imaging (MRI) scan of the brain showed symmetrical hyperintense lesions involving bilateral thalami and pons in T2-weighted and fluid-attenuated inversion recovery images. These lesions also presented with diffuse cerebral edema and diffusion restriction and subacute hemorrhage. Based on clinical symptoms and typical brain MRI, ANE was diagnosed, and the patient underwent immunotherapy.ConclusionsThis case underscores the occurrence of ANE triggered by bacterial infection, expanding our understanding of the pathogens associated with this condition. It suggests that ANE may be an immune-mediated disorder rather than solely an infectious disease.

8790 A Case Of Ectopic Cushing’s Syndrome Secondary To Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH)

Abstract Disclosure: T. Goettemoeller: None. R. Lopez Fanas: None. K. Cedeno: None. A. Manavalan: None. Introduction: Ectopic Cushing’s syndrome is a rare disease accounting for <20% of cases of endogenous Cushing’s syndrome. DIPNECH is a poorly understood lung disease characterized by abnormal proliferation of neuroendocrine cells in the bronchial mucosa. It can be a precursor to pulmonary carcinoid tumors and has rarely been associated with ACTH production. Clinical Case: A 70-year-old female with intellectual disability and hypertension presented with diffuse edema and weakness. Examination was notable for hypertension, anasarca, and hirsutism. In addition to hypokalemia and metabolic alkalosis, hypercortisolism was observed: random serum cortisol - 50.1 ug/dL, late-night salivary cortisol - 1.72 mcg/dL (normal < 0.09 mcg/dL) and 24-hour urine free cortisol - 1,845.9 mcg (normal: 4.0 – 50.0 mcg/24h). Cortisol level remained > 25 ug/dL after high-dose dexamethasone suppression test. Ketoconazole was initiated and titrated to achieve normal 24-hour urine free cortisol levels and spironolactone was added to manage hypokalemia. An MRI of the sella and pituitary was unremarkable while an abdomen and chest CT identified a 2.5 cm well-circumscribed right middle lobe pulmonary nodule and mild thickening of the bilateral adrenal glands. A gallium-DOTATATE scan revealed a 2.1 cm right middle lobe pulmonary nodule with mildly increased uptake. A transbronchial biopsy of the right middle lobe nodule confirmed a carcinoid tumor. Immunohistochemistry (IHC) staining was positive for CHR, SYN, CD56, and AE1/3. Ki-67 stain showed a low proliferative index. A right middle lobectomy was performed with pathology revealing two typical carcinoid tumors measuring 2.8 and 0.7 cm each, with multiple carcinoid tumorlets and foci of neuroendocrine cell hyperplasia consistent with DIPNECH. IHC staining for ACTH was positive in the carcinoid tumors and tumorlets. Four days after surgery, AM cortisol was 8.1 ug/dL and potassium levels and blood pressure normalized off ketoconazole and spironolactone. The patient was discharged, but was readmitted a month later for anasarca, lethargy, hypokalemia, and metabolic alkalosis. A recurrence of Cushing’s syndrome was confirmed, and medical therapy was resumed. A chest CT revealed post-surgical changes. Her course was complicated by an aspiration event, septic shock, PEA arrest, resuscitation, and intubation. The patient’s care was ultimately transitioned to hospice. Conclusion: Florid Cushing’s syndrome due to ectopic ACTH production associated with DIPNECH is an exceedingly rare condition. Early recognition and treatment are crucial to prevent the numerous complications that may arise, and close follow-up after tumor removal is critical to ensure continued remission has been achieved. Presentation: 6/1/2024

8790 A Case of Ectopic Cushing’s Syndrome Secondary to Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH)

Abstract Disclosure: T. Goettemoeller: None. R. Lopez Fanas: None. K. Cedeno: None. A. Manavalan: None. Introduction: Ectopic Cushing’s syndrome is a rare disease accounting for <20% of cases of endogenous Cushing’s syndrome. DIPNECH is a poorly understood lung disease characterized by abnormal proliferation of neuroendocrine cells in the bronchial mucosa. It can be a precursor to pulmonary carcinoid tumors and has rarely been associated with ACTH production. Clinical Case: A 70-year-old female with intellectual disability and hypertension presented with diffuse edema and weakness. Examination was notable for hypertension, anasarca, and hirsutism. In addition to hypokalemia and metabolic alkalosis, hypercortisolism was observed: random serum cortisol - 50.1 ug/dL, late-night salivary cortisol - 1.72 mcg/dL (normal < 0.09 mcg/dL) and 24-hour urine free cortisol - 1,845.9 mcg (normal: 4.0 – 50.0 mcg/24h). Cortisol level remained > 25 ug/dL after high-dose dexamethasone suppression test. Ketoconazole was initiated and titrated to achieve normal 24-hour urine free cortisol levels and spironolactone was added to manage hypokalemia. An MRI of the sella and pituitary was unremarkable while an abdomen and chest CT identified a 2.5 cm well-circumscribed right middle lobe pulmonary nodule and mild thickening of the bilateral adrenal glands. A gallium-DOTATATE scan revealed a 2.1 cm right middle lobe pulmonary nodule with mildly increased uptake. A transbronchial biopsy of the right middle lobe nodule confirmed a carcinoid tumor. Immunohistochemistry (IHC) staining was positive for CHR, SYN, CD56, and AE1/3. Ki-67 stain showed a low proliferative index. A right middle lobectomy was performed with pathology revealing two typical carcinoid tumors measuring 2.8 and 0.7 cm each, with multiple carcinoid tumorlets and foci of neuroendocrine cell hyperplasia consistent with DIPNECH. IHC staining for ACTH was positive in the carcinoid tumors and tumorlets. Four days after surgery, AM cortisol was 8.1 ug/dL and potassium levels and blood pressure normalized off ketoconazole and spironolactone. The patient was discharged, but was readmitted a month later for anasarca, lethargy, hypokalemia, and metabolic alkalosis. A recurrence of Cushing’s syndrome was confirmed, and medical therapy was resumed. A chest CT revealed post-surgical changes. Her course was complicated by an aspiration event, septic shock, PEA arrest, resuscitation, and intubation. The patient’s care was ultimately transitioned to hospice. Conclusion: Florid Cushing’s syndrome due to ectopic ACTH production associated with DIPNECH is an exceedingly rare condition. Early recognition and treatment are crucial to prevent the numerous complications that may arise, and close follow-up after tumor removal is critical to ensure continued remission has been achieved. Presentation: 6/1/2024

Association Between SARS-CoV-2 Infection and Acute Ischemic Colitis.

Ischemic colitis appears to be a rare but serious complication of COVID-19. About 33.3% hospitalized COVID-19 patients who underwent endoscopy showed features resembling ischemic colitis. The aim of this prospective study was to describe the symptoms, treatment, and outcomes of these patients, particularly their colonoscopy and histologic findings. We conducted a prospective study on ischemic bowel disease associated with COVID-19 across four centers from December 2022 to January 2023. All cases were identified through a comprehensive search of electronic medical records for procedure-related data. The initial diagnosis of ischemic bowel disease was confirmed using colonoscopy and biopsy findings. After the patients were discharged, a 12-month follow-up was conducted through regular phone interviews to assess their clinical outcomes. Overall, the study included 3 male patients and 9 female patients (age range, 33-76 years). Abdominal pain and hematochezia always occurred within 2weeks after COVID-19 infection (average 5.5 days). Gastrointestinal manifestations did not parallel the severity of COVID-19 infection. The descending colon was the most susceptible segment, which was involved in 10 patients (83.33%). Colonoscopy revealed diffuse redness, edema, bleeding, erosion, and ulceration of the intestinal mucosa, similar to the findings of ischemic colitis, and biopsy revealed crypt atrophy, reduction, and interstitial bleeding. All patients were self-limited without converting to chronic changes in the next 12 months. SARS-CoV-2 infection may induce transient acute colon ischemia within 2weeks, accompanied by severe clinical symptoms such as acute abdominal pain and hematochezia, which are self-limiting and do not lead to chronic symptoms.

A Splice Site Variant in ADAMTS3 Is the Likely Causal Variant for Pulmonary Hypoplasia with Anasarca in Persian/Persian-Cross Sheep.

Pulmonary hypoplasia with anasarca, or hydrops fetalis, is characterized by stillbirth, diffuse oedema, and generalized lymph node hypoplasia. The enlarged fetus frequently causes dystocia. The disease has been reported in cattle and sheep as an inherited condition with a recessive mode of inheritance. This is the first report of the disease in Persian/Persian-cross sheep in Australia. Affected fetuses were reported from three flocks, and a total of eleven affected, eleven obligate carrier, and 188 related Persian/Persian-cross animals were available for analysis, as well as unrelated control animals. SNP genotyping revealed a region of homozygosity in affected animals on ovine chromosome six, which contained the functional candidate gene ADAMTS3. Whole genome sequencing of two affected fetuses and one obligate carrier ewe revealed a single nucleotide deletion, ENSOARG00000013204:g.87124344delC, located 3 bp downstream from a donor splice site region in the ADAMTS3 gene. Sanger sequencing of cDNA containing this variant further revealed that it is likely to introduce an early splice site in exon 14, resulting in a loss of 6 amino acids at the junction of exon 14 and intron 14/15. A genotyping assay was developed, and the ENSOARG00000013204:g.87124344delC segregated with disease in 209 animals, allowing for effective identification of carrier animals.

Taurochenodeoxycholic acid ameliorates the Staphylococcus aureus infection-induced acute lung injury through toll-like receptor 2 in mice

Acute lung injury (ALI) is a significant clinical problem associated with high morbidity and mortality. Inflammation induced by gram-positive bacterial pathogens, specifically Staphylococcus aureus (S. aureus), plays a major role in ALI development and other infectious diseases. Taurochenodeoxycholic acid (TCDCA) exhibits diverse biological activities and pharmacological effects. Nevertheless, the potential preventive and therapeutic effects of TCDCA and the underlying mechanism in the ALI induced by S. aureus infection remain poorly understood. Our results showed that the TCDCA (0.1 μg/g) had a beneficial effect on lung damage in mice infected with S. aureus. Specifically, TCDCA could lead to a reduction in pulmonary focal or diffuse oedema and a decrease in the infiltration of neutrophils in the S. aureus-infected lungs. We observed that TCDCA could significantly down-regulate the expression of HMGB1 in lung from S. aureus-infected mice. Furthermore, TCDCA could attenuate the production of inflammatory mediators in lungs and serum from S. aureus-infected mice. This finding further supported the notion that TCDCA potentially protects against tissue injury. In addition, TCDCA regulated the secretion of the proinflammatory cytokine, the activation of MAPK and NF-κB signaling pathways, and the activation of TLR2 in macrophages. Notably, TCDCA might reduce the secretion levels of inflammatory mediators and lung damage through the TLR2 in S. aureus-infected macrophages or mice. Altogether, TCDCA shows promise as a potential drug for preventing and treating ALI by modulating or inhibiting inflammatory mediators through TLR2.

A fatal pediatric case of acute fulminant cerebral edema with COVID-19 in Korea: a case report

Although most children with coronavirus disease 2019 (COVID-19) infection present with mild symptoms, a few pediatric patients develop severe neurological manifestations. Herein, we describe the case of a pediatric patient who presented with rapidly progressive diffuse and fatal cerebral edema associated with COVID-19. A previously healthy 6-year-old boy was diagnosed with acute fulminant cerebral edema (AFCE), which resulted in transtentorial downward herniation within 48 hours after the initial onset of fever. Detailed history-taking, close monitoring of the consciousness level with serial neurological examinations, and prompt diagnosis and treatment are required in patients suspected to have AFCE. Further research is needed to identify the pathogenesis of AFCE associated with COVID-19 and the related risk factors.

Giant unruptured middle cerebral artery aneurysm revealed by intracranial hypertension: is a systematic decompressive hemicraniotomy mandatory?

Our study aimed to evaluate the postoperative outcome of patients with unruptured giant middle cerebral artery (MCA) aneurysm revealed by intracranial hypertension associated to midline brain shift. From 2012 to 2022, among the 954 patients treated by a microsurgical procedure for an intracranial aneurysm, our study included 9 consecutive patients with giant MCA aneurysm associated to intracranial hypertension with a midline brain shift. Deep hypothermic circulatory flow reduction (DHCFR) with vascular reconstruction was performed in 4 patients and cerebral revascularization with aneurysm trapping was the therapeutic strategy in 5 patients. Early (< 7 days) and long term clinical and radiological monitoring was done. Good functional outcome was considered as mRS score ≤ 2 at 3 months. The mean age at treatment was 44 yo (ranged from 17 to 70 yo). The mean maximal diameter of the aneurysm was 49 mm (ranged from 33 to 70 mm). The mean midline brain shift was 8.6 mm (ranged from 5 to 13 mm). Distal MCA territory hypoperfusion was noted in 6 patients. Diffuse postoperative cerebral edema occurred in the 9 patients with a mean delay of 59 h and conducted to a postoperative neurological deterioration in 7 of them. Postoperative death was noted in 3 patients. Among the 6 survivors, early postoperative decompressive hemicraniotomy was required in 4 patients. Good functional outcome was noted in 4 patients. Complete aneurysm occlusion was noted in each patient at last follow-up. We suggest to discuss a systematic decompressive hemicraniotomy at the end of the surgical procedure and/or a partial temporal lobe resection at its beginning to reduce the consequences of the edema reaction and to improve the postoperative outcome of this specific subgroup of patients. A better intraoperative assessment of the blood flow might also reduce the occurrence of the reperfusion syndrome.

Pink urine syndrome in an anuric patient during continuous renal replacement therapy: A case report.

Pink urine syndrome is a rare, poorly understood condition, often prompted by obesity, insulin resistance, and the drug propofol. It is characterized by pink urine or urine sediment and occurs in the absence of a heme or food-based pigment. The pathophysiology of this syndrome is not yet fully understood but is linked to a uric acid metabolism disorder. Pink urine syndrome is less familiar to anesthesiologists than other propofol infusion complications. Our case report aims to highlight this rarely encountered syndrome, whose both diagnosis and therapeutic may be challenging. We have reported the first case of this syndrome evidenced by the change in color of the effluent bag during continuous veno-venous hemofiltration (CVVHF). A 61-year-old woman was admitted to the intensive care unit following a recovered cardiorespiratory arrest due to ventricular arrhythmia. She was placed in hypothermia, sedated with propofol (300 mg/h), and started on CVVHF for oligo-anuric acute kidney injury associated with severe metabolic acidosis. A few hours after initiation of CVVHF, the effluent bag turned bright pink. Given the pink color of the effluent bag and the hypothesis of propofol-induced pink urine syndrome, propofol was replaced by midazolam. After stopping propofol, the color of effluent bag lightened. Unfortunately, the patient died on the third day of hospitalization due to diffuse cerebral edema. We report here the first case of pink urine syndrome as revealed by the change in color of the contents of the CVVHF effluent bag in an anuric patient. This syndrome is rare but significant in anesthesia/intensive care settings, where propofol is a frequently used sedative. Knowledge of this syndrome appears to be important to avoid irrelevant additional investigations and to optimize the therapeutic strategy.

Unusual metastases to the breast from different extramammary malignancies: a multimodality imaging approach in a case series.

Extramammary metastases are uncommon and usually related to a poor prognosis, but the radiologist can suspect the diagnosis based on the patient's clinical history and specific imaging findings. Several imaging procedures may be used to evaluate breast metastases from different extramammary malignancies, including mammography, ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography-CT (PET-CT). The clinical and imaging presentation of these metastases is contingent upon how the illness spreads, however, they have the potential to resemble either benign or malignant breast tumors. Metastases that disseminate hematologically tend to appear as a single round or oval mass with circumscribed margins. Sonographically, they are usually hypoechoic, and with CT or MRI, they usually enhance. Lymphatic dissemination, for example, frequently reveals significant asymmetry with skin thickening and diffuse breast edema, which is compatible with an inflammatory breast carcinoma. Knowing the many types of cancers that have the potential to spread to the breast as well as being able to accurately diagnose them is crucial to prevent a needless mastectomy and provide guidance for subsequent treatment. The purpose of this article is to provide a better understanding of the imaging features and immunohistochemistry (IHC) of secondary tumors of the breast by presenting eight distinctive cases, which will enable radiologists to recognize this entity.

CPT1A-IL-10-mediated macrophage metabolic and phenotypic alterations ameliorate acute lung injury.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common acute respiratory failure due to diffuse pulmonary inflammation and oedema. Elaborate regulation of macrophage activation is essential for managing this inflammatory process and maintaining tissue homeostasis. In the past decades, metabolic reprogramming of macrophages has emerged as a predominant role in modulating their biology and function. Here, we observed reduced expression of carnitine palmitoyltransferase 1A (CPT1A), a key rate-limiting enzyme of fatty acid oxidation (FAO), in macrophages of lipopolysaccharide (LPS)-induced ALI mouse model. We assume that CPT1A and its regulated FAO is involved in the regulation of macrophage polarization, which could be positive regulated by interleukin-10 (IL-10). After nasal inhalation rIL-10 and/or LPS, wild type (WT), IL-10-/-, Cre-CPT1Afl/fl and Cre+CPT1Afl/fl mice were sacrificed to harvest bronchoalveolar lavage fluid, blood serum and lungs to examine cell infiltration, cytokine production, lung injury severity and IHC. Bone marrow-derived macrophages (BMDMs) were extracted from mice and stimulated by exogenous rIL-10 and/or LPS. The qRT-PCR, Seahorse XFe96 and FAO metabolite related kits were used to test the glycolysis and FAO level in BMDMs. Immunoblotting assay, confocal microscopy and fluorescence microplate were used to test macrophage polarization as well as mitochondrial structure and function damage. In in vivo experiments, we found that mice lacking CPT1A or IL-10 produced an aggravate inflammatory response to LPS stimulation. However, the addition of rIL-10 could alleviate the pulmonary inflammation in mice effectively. IHC results showed that IL-10 expression in lung macrophage decreased dramatically in Cre+CPT1Afl/fl mice. The in vitro experiments showed Cre+CPT1Afl/fl and IL-10-/- BMDMs became more "glycolytic", but less "FAO" when subjected to external attacks. However, the supplementation of rIL-10 into macrophages showed reverse effect. CPT1A and IL-10 can drive the polarization of BMDM from M1 phenotype to M2 phenotype, and CPT1A-IL-10 axis is also involved in the process of maintaining mitochondrial homeostasis. CPT1A modulated metabolic reprogramming and polarisation of macrophage under LPS stimulation. The protective effects of CPT1A may be partly attributed to the induction of IL-10/IL-10 receptor expression.

The emerging role of cardiovascular magnetic resonance in the evaluation of cardiac involvement in systemic sclerosis

Abstract Systemic sclerosis (SSc) is an autoimmune rheumatic disease, characterized by vascular, inflammatory and fibrotic alterations. Cardiac involvement is the « fatal tip of the iceberg» in SSc, as it leads to high morbidity/mortality. Cardiovascular imaging modalities play an important role in the early diagnosis and treatment assessment of cardiac involvement. Echocardiography is the corner stone for evaluation of cardiac involvement, providing information about function, wall motion, pulmonary pressure, pericardium and valvular disease. It is a low-cost modality, widely available, without radiation and with great experience among cardiologists. However, it is a window and operator dependent modality and cannot provide tissue characterization information, absolutely necessary for diagnosis and treatment of cardiac involvement in SSc. Cardiovascular magnetic resonance (CMR) can perform myocardial function and tissue characterization in the same examination without radiation, has excellent reproducibility and is window and operator independent. The great advantage of CMR is the capability to assess peri- myo-vascular inflammation, myocardial ischemia and presence of replacement and diffuse myocardial fibrosis in parallel with ventricular function assessment. The modified Lake Louise criteria including T2, native T1 mapping and extracellular volume fraction (ECV) has been recently used to diagnose inflammatory cardiomyopathy. According to expert recommendations, myocardial inflammation should be considered if at least 2 indices, one T2 and one T1 parameter are positive, whereas native T1 mapping and ECV assess diffuse fibrosis or oedema, even in the absence of late gadolinium enhancement (LGE). Moreover, transmural/subendocardial LGE following the distribution of coronary arteries and diffuse subendocardial fibrosis not related with epicardial coronary arteries are indicative of epicardial and micro-vascular coronary artery disease, respectively. To conclude, CMR can overcome the limitations of echocardiography by identifying acute/active or chronic myocardial inflammation/fibrosis, ischemia and myocardial infarction using classic and parametric indices in parallel with biventricular function assessment

The Silent Threat: Unraveling the Rare Catastrophic Complication after Elective Cranioplasty

AbstractAlthough cranioplasty seems to be a simple procedure, fatal complication of development of diffuse severe cerebral edema following cranioplasty although unusual have been reported in a few cases. The mechanism for this occurrence is still speculative. A 38-year-old male patient presented with a history of having undergone left decompressive hemicraniectomy following a road traffic accident with traumatic left intracranial internal carotid artery dissection leading to anterior cerebral artery and middle cerebral artery territory infarct and endovascular embolization of traumatic type 1 left caroticocavernous fistula. The preoperative computed tomography scan of the brain revealed left frontotemperoparietal craniectomy defect with sunken flap and diffuse encephalomalacia with gliosis of the entire left cerebral hemisphere. Immediately following an uneventful cranioplasty surgery with titanium mesh, the patient developed severe hypotension and dilated fixed pupils. Postoperative imaging revealed diffuse severe cerebral edema in bilateral hemispheres with a significant midline shift toward the ipsilateral (left) side, that is, toward the side of cranioplasty. The patient immediately underwent removal of the titanium mesh, and despite all efforts, the patient had a fatal outcome on postoperative day 5. Although this type of fatal complication of diffuse severe cerebral edema is rare in postcranioplasty patients, neurosurgeons must be aware of this complication and close monitoring postprocedure is important, especially in patients with a large craniectomy defect and sunken skin flap.

VASCULAR PARKINSONISM WITH EARLY COGNITIVE IMPAIRMENT: A CASE REPORT AND LITERATURE REVIEW

Cerebral venous sinus thrombosis (CVST) is an uncommon condition of cerebral venous sinus thrombosis with a varied clinical presentation that can be diagnostically challenging. Intravenous heparin is the optimal immediate anticoagulant according to the European Academy of Neurology (EAN) guideline 2017. This report aims to describe highly suspicious CVST clinical features and suggest a diagnostic algorithm based on two cases of CVST found in our center. The first case is a 52-year-old man who presented with serial seizures preceded by subacute headache and diparesis. Non-contrast head CT (NCCT) showed multifocal haemorrhages and cord signs. The second case is a 19-year-old woman who presented with slowly decreased consciousness, headache, and a history of upper respiratory infection. Diffuse cerebral edema was revealed in NCCT. Both of these patients had thrombosis in superior sagittal sinus, right transverse, and sigmoid sinus. Heparinization was conducted and continued with rivaroxaban with a good response. CVST is rare case and often unrecognized; since it has serious complications, early diagnosis and treatment improve prognosis and survival.

IMG-03. PRE-TREATMENT EVIDENCE OF ABNORMAL SUPRATENTORIAL WHITE MATTER IN CHILDREN WITH POSTERIOR FOSSA TUMOURS USING DIFFUSION MRI

Abstract BACKGROUND Over half of childhood brain tumours originate in the posterior fossa, which includes low-grade (e.g. pilocytic astrocytoma) and high-grade (e.g. medulloblastoma) tumours. Even though overall survival rates of paediatric brain tumours have substantially increased, survivors face neuropsychological impairments impacting behaviour, cognition, language and motor skills. Post-treatment outcomes are associated with structural changes within the brain, but it is unclear if observed microstructural damage is caused exclusively by radiotherapy or if there is earlier damage from the tumour and related effects. Diffusion MRI is a non-invasive technique that can be used to better understand white matter microstructure by quantifying water diffusion in the brain. Diffusion tensor imaging (DTI) can be used to assess white matter damage. METHODS In this work, we used DTI to understand white matter microstructure in 8 posterior fossa tumour patients prior to surgery. We compared individual patients to age- and sex-matched healthy controls in a one-against-many approach. RESULTS We demonstrate the presence of supratentorial white matter abnormalities prior to treatment in 3 patients. Before treatment, all patients are found to have significantly enlarged lateral ventricles relative to total brain volume (p&amp;lt;0.05). Patients with ventricle volumes &amp;gt;4% relative to brain volume correspond to significant changes in DTI parameters found in pre-treatment images, suggesting that hydrocephalus impacts white matter microstructure before surgery. Observed white matter changes are complex and patient-dependent, patients demonstrate compression (increased fractional anisotropy; FA) or diffuse oedema and damage (decreased FA). These white matter abnormalities persist over time, which could lead to cumulative damage, for example when adjuvant treatment involves radiotherapy. CONCLUSIONS To improve patient outcomes, pre-treatment imaging could be considered during individual treatment planning and risk evaluation to avoid further injury to white matter. Pre-treatment white matter abnormalities may have a bearing on neurocognitive patient outcomes, which will be the focus of future work.

Primary Amoebic Meningoencephalitis with Progression to Brain Death Following Naegleria Fowleri Infection in a Teenage Female

Abstract Naegleria fowleri is a high-temperature freshwater-living amoeba that causes primary amoebic meningoencephalitis (PAM) by invading nasal epithelium. N. fowleri lives ubiquitously in high-temperature freshwater, but only around 400 cases of PAM have been published worldwide. The mortality rate is 98%. No treatment is 100% effective. A previously healthy 17-year-old female presented to an urgent care center with fever, headache, sore throat, ear pain, and dizziness. She had swum in freshwater 5 days prior. Her symptoms progressed to altered mental status, photo- and phonophobia, and neck stiffness. Within 4 days, she developed increased intracranial pressure (ICP) and eventually brain death. Two unsuccessful lumbar punctures were attempted before the third provided cerebrospinal fluid (CSF) for polymerase chain reaction (PCR) analysis. Magnetic resonance imaging showed diffuse cerebral edema, effacement of basal cisterns, tonsillar herniation with diffuse loss of gray–white matter differentiation, leptomeningitis, bifrontal encephalitis with evolving frontal lobe cortical infarcts, and ventriculitis. She was treated with metronidazole, vancomycin, ceftriaxone, acyclovir, and doxycycline. Her increased ICP progressed to brain death, and she died 11 days after lake exposure. CSF PCR was reported positive for N. fowleri the day after her death. Despite advances in diagnostic testing for N. fowleri with PCR, mortality rate is high and current treatments are highly ineffective. This case highlights the importance of epidemiological exposure and considering PAM on the differential diagnosis. Although headache and fever are benign symptoms, they could also represent the first stages of a deadly disease and their progression should be addressed promptly.

MYOCARDITIS: VIRUS OR DESMOSOME?

Abstract Patient Profile Female, 56 yo, arterial hypertension, FH of autoimmune diseases, no history of sudden death. Medical History: • At the age of 46: Hospitalized for chest pain. Coronary angiography: negative. Diagnosis: myocardial ischemia with normal coronary arteries. • 2018: Hospitalized again for angina. ECG showed low voltages, flat T–waves in the inf–lat. leads. Coronary angiography: negative. Biopsy Mild hypertrophy and cytoplasmic vacuolization, minimal increase in interstitial fibrosis, no necrosis or inflammatory infiltrates. Mild nonspecific cardiomyopathy. Viral DNA test positive for HHV–6. Serology: HHV–6 in blood (neg), IgG HHV–6 (pos), IgM (neg). Diagnosis: myocarditis due to HHV–6. • San Camillo Cardiomyopathy Center: Echocardiogram: basal ant–lat. hypokinesia, EF 60%. Therapy: Bisoprolol 3.75 mg, Ramipril 5 mg, Ranolazine 1000 mg. MRI: basal transmural ant–lat. and subepicardial lateral LGE. Oedema and hypokinesia coexists. Subacute myocarditis. MRI at 1 year: mild left ventricular dilation, EF 60%, meso–subepicardial LGE in the ant–lat and inf mid–basal regions without oedema. Serial Holter ECGs: frequent polymorphic ventricular ectopics, couplets, and runs. CPET: normal exercise capacity, pVO2 19.4 (ml/min)/kg (90%). Genetic testing VUS in DSC, probably pathogenic, and VUS in ABCC9, PKP2, DSP (2 mutations) with uncertain clinical significance. • In 2022: Readmitted for angina. Elevated Troponin levels. Coro CT angiography: negative. MRI: EF 45%, akinesia of the apex and apical lat. wall; diffuse LGE and edema. Pericardial effusion. Patient refused biopsy. Discharged after recovery (EF 52%) with the diagnosis of recurrent myocarditis. Empagliflozin added. • Follow up. ECG: progression of repolarization abnormalities (TWI in V1–V3 + inf.–lat. leads). Biopsy: fibroadipose replacement, no necrosis or inflammatory infiltrates. Chronic myocarditis and sequels. Viral tests: negative. CPET and stress echo: VO2peak 20.7 (ml/kg)/min (88%), normal work capacity. Very rare monomorphic PVCs. EF 50%, preserved contractile reserve. Conclusions Diagnosis of left dominant arrhythmogenic cardiomyopathy with a typical pattern for hot phases of myocardial inflammation. The first episode could have been triggered by a viral infection on a predisposing genetic substrate. Nadolol 40 mg x2 was introduced. The possibility of ICD implantation was discussed, and patient refused. A six–month follow–up was planned. Family screening results were negative.