Multiple Pathologies Research Articles

Abstract 406: Normalization Of Erythrocyte Morphology In Scarb1 -/- Mice By Bacterial Serum Opacity Factor Is Dependent On HDL-free Cholesterol

Compared to wild-type mice, HDL-receptor-deficient (Scarb1 -/- ) mice have higher plasma levels of free cholesterol (FC)-rich HDL and exhibit multiple pathologies—female infertility and deranged platelet and erythrocyte morphology and function. These pathologies are associated with a low mol% FC in ovaries, platelets, and erythrocytes, effects that are reversed by the HDL-lowering drug probucol. Some strains of Streptococcus pyogenes secrete a protein, serum opacity factor (SOF), which catalyzes the clouding i.e., opacification, of plasma. SOF specifically targets and quantitatively converts HDL into three products, that include a cholesteryl ester-rich microemulsion containing all the cholesterol content of >100,000 HDL particles as well as APOE and its heterodimer with APOA2 as its sole apolipoproteins. Delivery of SOF with an adeno-associated virus (AAV SOF ) constitutively lowers plasma HDL-FC and reverses female infertility in Scarb1 -/- mice. Thus, we tested the hypothesis—AAV SOF delivery to Scarb1 -/- mice will normalize erythrocyte morphology in an HDL-FC dependent way. The erythrocyte morphology and FC content expressed as mol% FC of three groups of mice—WT, untreated Scarb1 -/- mice (control) and Scarb1 -/- mice receiving AAV SOF —were compared and correlated with their respective HDL-mol% FC. Among Scarb1 -/- mice, AAV SOF treatment normalized reticulocyte number, erythrocyte morphology and erythrocyte mol% FC. Plasma- and HDL-mol% FC positively correlated (p < 0.0001) across all three groups of mice. HDL-mol% FC also positively correlated with erythrocyte mol% FC (p < 0.0001). Finally, the erythrocyte mol% FC positively correlated with both the number of reticulocytes (p = 0.006) and abnormal erythrocytes (p < 0.0001). Although less profound, AAV SOF treatment also reduced the FC contents of some extravascular tissues. HDL-FC spontaneously transfers from plasma lipoproteins to cell membranes in multiple tissues sites on a time scale of minutes to a few hours. FC-enrichment of erythrocytes, which are in contact with plasma HDL, was more profound than FC enrichment in tissues. AAV SOF treatment lowers both plasma HDL-FC and erythrocyte-FC and normalizes erythrocyte morphology and lipid composition in an HDL-FC dependent way.

Could hyperlipidemia be a risk factor for corticobasal syndrome? - a pilot study.

Corticobasal syndrome (CBS) is a specific clinical manifestation shared by multiple pathologies. The exact mechanism of this phenomenon remains unclear. Differential diagnosis of CBS in everyday clinical practice is challenging, as this syndrome can overlap with other entities, especially progressive supranuclear palsy Richardson-Steele phenotype (PSP-RS). Several papers have suggested a possible role of vascular pathology as a linking factor in the pathogenesis of CBS based on different neuropathologies. This paper analyses differences in the occurrence of the most common vascular risk factors such as hypertension and lipid profile with respect to dietary habits among patients who fulfill the diagnostic criteria for probable/possible CBS and PSP-RS. Seventy (70) patients in total were included in the study. Exclusion criteria comprised hydrocephalus, stroke in the past, the presence of marked vascular changes in white matter defined as the presence of vascular change ≥ 1 mm in 3T MRI, medical history of hyperlipidemia or the use of drugs that could impact upon lipid metabolism before the initiation of the neurodegenerative disease, and neoplastic focuses in the central nervous system. Patients with diabetes, or with BMI exceeding 18-25, or who were smokers, or who were affected by chronic stress were also excluded. Data was analysed statistically using the Shapiro-Wilk test, the U Mann-Whitney test for group comparison, and a Bonferroni correction to control the false discovery rate (FDR). Our obtained results indicated a statistically significantly higher level of total cholesterol in the CBS group (p = 0.0039) without a correlation with dietary habits. The results obtained in our study may suggest a possible role of vascular pathology in CBS development. This issue requires further research.

Intrinsic features of the cancer cell as drivers of immune checkpoint blockade response and refractoriness.

Immune checkpoint blockade represents the latest revolution in cancer treatment by substantially increasing patients' lifetime and quality of life in multiple neoplastic pathologies. However, this new avenue of cancer management appeared extremely beneficial in a minority of cancer types and the sub-population of patients that would benefit from such therapies remain difficult to predict. In this review of the literature, we have summarized important knowledge linking cancer cell characteristics with the response to immunotherapy. Mostly focused on lung cancer, our objective was to illustrate how cancer cell diversity inside a well-defined pathology might explain sensitivity and refractoriness to immunotherapies. We first discuss how genomic instability, epigenetics and innate immune signaling could explain differences in the response to immune checkpoint blockers. Then, in a second part we detailed important notions suggesting that altered cancer cell metabolism, specific oncogenic signaling, tumor suppressor loss as well as tight control of the cGAS/STING pathway in the cancer cells can be associated with resistance to immune checkpoint blockade. At the end, we discussed recent evidences that could suggest that immune checkpoint blockade as first line therapy might shape the cancer cell clones diversity and give rise to the appearance of novel resistance mechanisms.

Sister Marie Joseph Nodule in a Polypathological Patient: Study of an Observation at the Dermatology Hospital of Bamako (Mali)

Summary: Sister Mary Joseph nodule is a metastatic localization with a generally abdominal-pelvic origin and secondary to a primary adenocarcinoma in 90% of cases. We report an observation of Sister Mary Joseph nodule revealing a primary adenocarcinoma of the colon in a young adult with multiple pathologies. Observation: A 57-year-old patient, followed for hepatitis B, HIV1+, and benefiting from a therapeutic regimen (Tenofovir+Lamivudine+Dolutegravir) since 2019 and later a hyperthyroidism of incidental discovery. For one year he has had a firm nodular ulceration measuring 07 cm in its longest axis, with a reddish-pink appearance and whitish deposits, a haemorrhagic ooze on contact, and located at the umbilicus. Also, a tongue laden with whitish coatings that are easily removed with a tongue depressor and the inner surface of the cheeks and palate are erythematous. Bilateral exophthalmos abolished vocal vibrations in both lung bases; two hard left inguinal adenopathies adhering to the deep plane, painless, 3 cm in diameter each. He also described episodes of alternating constipation and diarrhoea accompanied by abdominal pain, coughing, physical asthenia and weight loss (40% loss in 2 years). Anatomopathology of a fragment of the nodule revealed a well-differentiated adenocarcinoma whose tumour cells were of colorectal origin and expressed CK20 and CK8/18. Colonoscopy revealed a multilobed polyploid tumour of the ascending colon and histology concluded that it was a liberkuhnian adenocarcinoma. A chest CT scan revealed pulmonary and abdominal-pelvic metastases and the diagnosis of a Sister Mary Joseph nodule revealing a colonic and metastatic adenocarcinoma was made. The patient was referred to the oncology department for palliative care after the surgical opinion. Conclusion: The nodule of Sister Marie Joseph is a cutaneous metastasis revealing a cancer of the abdominopelvic sphere. This rare and characteristic tumour deserves to be known by practitioners .......

Comparative Study of Time-Dependent Aluminum Exposure and Post-Exposure Recovery Shows Better Improvement in Synaptic Changes andNeuronal Pathology in Rat Brain After Short-Term Exposure.

Aluminum is a ubiquitous metal that causes multiple brain pathologies such as, cognitive dysfunction and Alzheimer's disease like symptoms. Exposure to aluminum through drinking water is responsible for hampering learning and memory. This study aimed to compare (1) the time-dependent effect of aluminum exposure (keeping total exposure of 5850mg/kg same) in two durations, 30 and 45days, and (2) to compare post-exposure self-recovery effect after 20days in both (30 and 45days exposure) groups. Rats were given 130 and 195mg/kg of AlCl3·6H2O for 45 and 30days respectively, to see the time-dependent exposure effect. At the end of exposure, rats were given distilled water and allowed to self-recover for 20days to study the recovery. Expressionlevelsof synaptic genes (Syp, SNAP25, Nrxn1/2, PSD95, Shank1/2, Homer1, CamkIV, Nrg1/2 and Kalrn) were measured using qPCR and compared in the exposure and recovery groups. Cellular morphology of the rat brain cortex and hippocampus was also investigated. Damage in lipid and protein profile was measured by employing FTIR. Results showed downregulation of mRNA expression of synaptic genes, plaques deposition, disorganization in lipid and protein profile by increasing membrane fluidity, and disorder and alteration of protein secondary structure after both exposure periods. However, better improvement/recovery in these parameters were observed in recovery group of 30days aluminum exposure compared to 45days aluminum exposure group. Taken together, these results suggested that short-term exposure resulted in better restoration of lipid and protein profile after time-dependent exposure of aluminum than prolonged exposure.

Soft Tissue Benign Hand Masses in the First Web Space: A Retrospective Case Series.

Hand masses arefairly common. While most of these massesare either ganglion cysts or benign tumors, masses in the first web space are not rare, and they may in fact represent a variety of lesions. These include both benign and malignant tumors, metastases, or congenital and anomalous structures, and may involve nerves, vascular structures, connective tissue, and joints. In this retrospective case series, data on 12 cases of first dorsal web space hand mass treated at our center over a period of five years were collected and analyzed. Twelve consecutive patients presenting with a first dorsal web space hand massover a period of five years were reviewed.This represented a group of nine females and three males, with a mean age of 53 years (range = 16-70 years). Seven patients had a mass on the right side and five on the left side. The surgical approach to resect the mass in all 12 patients was dorsal. The most common diagnosis was ganglion cyst(50%), followed by lipoma(25%) and aneurysm(16.6%).There was one case of eccrinespiradenoma. Firstdorsal web space hand masses can encompass multiple different pathologies, and the first web space has an intricate anatomy.Both of these factors mandatea careful approach that includes meticulous preoperative planning with appropriate advanced imaging studies, which helps to make the surgical procedure more efficient and accurate.

Foveal avascular zone segmentation using deep learning-driven image-level optimization and fundus photographs.

The foveal avascular zone (FAZ) is a retinal area devoid of capillaries and associated with multiple retinal pathologies and visual acuity. Optical Coherence Tomography Angiography (OCT-A) is a very effective means of visualizing retinal vascular and avascular areas, but its use remains limited to research settings due to its complex optics limiting availability. On the other hand, fundus photography is widely available and often adopted in population studies. In this work, we test the feasibility of estimating the FAZ from fundus photos using three different approaches. The first two approaches rely on pixel-level and image-level FAZ information to segment FAZ pixels and regress FAZ area, respectively. The third is a training mask-free pipeline combining saliency maps with an active contours approach to segment FAZ pixels while being trained on image-level measures of the FAZ areas. This enables training FAZ segmentation methods without manual alignment of fundus and OCT-A images, a time-consuming process, which limits the dataset that can be used for training. Segmentation methods trained on pixel-level labels and image-level labels had good agreement with masks from a human grader (respectively DICE of 0.45 and 0.4). Results indicate the feasibility of using fundus images as a proxy to estimate the FAZ when angiography data is not available.

Chapter 17: Vascular Lesions

Vascular diseases are among the most common disorders that neurologists treat on a daily basis. Ischemic stroke is generally what comes to mind on mention of vascular disorders. However, the term is inclusive of multiple other pathologies. This chapter allows readers to appreciate the breadth of this field by exploring various types of vascular lesions. In addition to ischemic strokes, we will discuss cases of hemorrhagic strokes, vascular malformations, and other uncommon vascular entities such as dynamic occlusions and rare genetic disorders.

Remyelination by surviving oligodendrocytes is inefficient in the inflamed mammalian cortex

In multiple sclerosis, an inflammatory attack results in myelin loss, which can be partially reversed by remyelination. Recent studies suggest that mature oligodendrocytes could contribute to remyelination by generating new myelin. Here, we show that in a mouse model of cortical multiple sclerosis pathology, surviving oligodendrocytes can indeed extend new proximal processes but rarely generate new myelin internodes. Furthermore, drugs that boost myelin recovery by targeting oligodendrocyte precursor cells did not enhance this alternate mode of myelin regeneration. These data indicate that the contribution of surviving oligodendrocytes to myelin recovery in the inflamed mammalian CNS is minor and inhibited by distinct remyelination brakes.

Growing old together: What we know about the influence of diet and exercise on the aging host's gut microbiome.

The immune system is critical in defending against infection from pathogenic microorganisms. Individuals with weakened immune systems, such as the elderly, are more susceptible to infections and developing autoimmune and inflammatory diseases. The gut microbiome contains a plethora of bacteria and other microorganisms, which collectively plays a significant role in immune function and homeostasis. Gut microbiota are considered to be highly influential on host health and immune function. Therefore, dysbiosis of the microbiota could be a major contributor to the elevated incidence of multiple age-related pathologies. While there seems to be a general consensus that the composition of gut microbiota changes with age, very little is known about how diet and exercise might influence the aging microbiome. Here, we examine the current state of the literature regarding alterations to the gut microbiome as hosts age, drawing particular attention to the knowledge gaps in addressing how diet and exercise influence the aging microbiome. Further, we will demonstrate the need for more controlled studies to investigate the roles that diet and exercise play driving the composition, diversity, and function of the microbiome in an aging population.

The Choice of Tactics for Surgical Treatment of Acute De Bakey Type I Aortic Dissection in a Multidisciplinary Surgical Hospital

BACKGROUND Acute proximal aortic dissection (Stanford type A) remains the most common fatal pathology of the thoracic aorta. Despite the improvement of surgical technologies, hospital mortality after emergency surgical interventions is 17–25%, in complicated cases it can reach 80–90%.AIM OF STUDY Description of the perioperative treatment tactics adopted at the N.V. Sklifosovsky Research Institute for Emergency Medicine as well as the evolution of approaches that make it possible to obtain satisfactory hospital and long-term results in the treatment of aortic dissection.MATERIAL AND METHODS the study included 278 patients operated on from 2015 to 2021 in the acute stage of aortic dissection (less than 48 hours from the moment of manifestation of the disease). The operated patients were divided into two groups, depending on the presence of complicated forms: group A, 102 patients with uncomplicated course of the disease; group B, 176 patients with complicated course of the disease. Additionally, patients were divided depending on the level of distal reconstruction performed: group I, 83 patients, surgery was limited to prosthetics of the ascending aorta, without removing the clamp; group II, 137 patients who underwent hemi-arch surgery; group III, 58 patients, with distal reconstruction involving the aortic arch.RESULTS Total hospital mortality was 28.1%: 25.3% in group I, 29.1% in group II, 29.3% in group III. In the group of uncomplicated dissection, postoperative mortality was 18.6%, while in the group of complicated dissection it was 33.5%.CONCLUSION An integrated multidisciplinary approach with the formation of an “aortic team”, an individual approach to surgery, depending on the anatomy of the dissection and the clinical status of the patient, will improve the results of the treatment of acute aortic dissection, as the most severe and multiple organ pathology of the aorta.FINDING 1. Hospital mortality of complicated forms of dissection remains significantly higher — 33.5% versus 18.5% of uncomplicated course. 2. The most optimal method of distal reconstruction in patients with the peracute stage of dissection is an open anastomosis with the aorta using the “hemi-arch” technique. 3. If it is necessary to extend the surgical intervention on the aortic arch, a distal anastomosis in areas 0, 1, 2 with the possibility of a subsequent endovascular stage is the priority.

Magnetic resonance imaging of fetal abdominal pathology: a complementary tool to prenatal ultrasound.

Fetal magnetic resonance imaging (MRI) is increasingly being used worldwide as a complementary tool to prenatal ultrasound (US)for multiple fetal pathologies. The aim of this article is to describe and illustrate how MRI can help US to evaluate fetal abdominal anomalies, based on cases performed in a tertiary public university hospital. Prenatal US, fetal MRI and postnatal imaging of these cases will be shown side-by-side to describe and illustrate the added value of fetal MRI in the different organs/systems and its impact on clinical management.

Revisiting the Role of NAG across the Continuum of Kidney Disease.

Acute and chronic kidney diseases are an evolving continuum for which reliable biomarkers of early disease are lacking. The potential use of glycosidases, enzymes involved in carbohydrate metabolism, in kidney disease detection has been under investigation since the 1960s. N-acetyl-beta-D-glucosaminidase (NAG) is a glycosidase commonly found in proximal tubule epithelial cells (PTECs). Due to its large molecular weight, plasma-soluble NAG cannot pass the glomerular filtration barrier; thus, increased urinary concentration of NAG (uNAG) may suggest injury to the proximal tubule. As the PTECs are the workhorses of the kidney that perform much of the filtration and reabsorption, they are a common starting point in acute and chronic kidney disease. NAG has previously been researched, and it is widely used as a valuable biomarker in both acute and chronic kidney disease, as well as in patients suffering from diabetes mellitus, heart failure, and other chronic diseases leading to kidney failure. Here, we present an overview of the research pertaining to uNAG's biomarker potential across the spectrum of kidney disease, with an additional emphasis on environmental nephrotoxic substance exposure. In spite of a large body of evidence strongly suggesting connections between uNAG levels and multiple kidney pathologies, focused clinical validation tests and knowledge on underlining molecular mechanisms are largely lacking.

Chimeric Peptides from Californiconus californicus and Heterodontus francisci with Antigen-Binding Capacity: A Conotoxin Scaffold to Create Non-Natural Antibodies (NoNaBodies).

Research into various proteins capable of blocking metabolic pathways has improved the detection and treatment of multiple pathologies associated with the malfunction and overexpression of different metabolites. However, antigen-binding proteins have limitations. To overcome the disadvantages of the available antigen-binding proteins, the present investigation aims to provide chimeric antigen-binding peptides by binding a complementarity-determining region 3 (CDR3) of variable domains of new antigen receptors (VNARs) with a conotoxin. Six non-natural antibodies (NoNaBodies) were obtained from the complexes of conotoxin cal14.1a with six CDR3s from the VNARs of Heterodontus francisci and two NoNaBodies from the VNARs of other shark species. The peptides cal_P98Y vs. vascular endothelial growth factor 165 (VEGF165), cal_T10 vs. transforming growth factor beta (TGF-β), and cal_CV043 vs. carcinoembryonic antigen (CEA) showed in-silico and in vitro recognition capacity. Likewise, cal_P98Y and cal_CV043 demonstrated the capacity to neutralize the antigens for which they were designed.

Avidity-Based Method for the Efficient Generation of Monoubiquitinated Recombinant Proteins.

Monoubiquitination of proteins governs diverse physiological processes, and its dysregulation is implicated in multiple pathologies. The difficulty of preparing sufficient material often complicates the biophysical studies of monoubiquitinated recombinant proteins. Here we describe a robust avidity-based method that overcomes this problem. As a proof-of-concept, we produced milligram quantities of two monoubiquitinated targets, Parkinson's protein α-synuclein and ESCRT-protein ALIX, using NEDD4-family E3 ligases. Monoubiquitination hotspots were identified by quantitative chemical proteomics. Using FRAP and dye-binding assays, we uncovered strikingly opposite effects of monoubiquitination on the phase separation and fibrillization properties of these two amyloidogenic proteins, reflecting differences in their intermolecular interactions, thereby providing unique insights into the impact of monoubiquitination on protein aggregation.

The DNA methylome of human vascular endothelium and its use in liquid biopsies

Vascular endothelial cells (VECs) are an essential component of each tissue, contribute to multiple pathologies, and are targeted by important drugs. Yet, there is a shortage of biomarkers to assess VEC turnover. To develop DNA methylation-based liquid biopsies for VECs, we determined the methylome of VECs isolated from freshly dissociated human tissues. A comparison with a human cell-type methylome atlas yielded thousands of loci that are uniquely unmethylated in VECs. These sites are typically gene enhancers, often residing adjacent to VEC-specific genes. We also identified hundreds of genomic loci that are differentially methylated in organotypic VECs, indicating that VECs feeding specific organs are distinct cell types with a stable epigenetic identity. We established universal and lung-specific VEC markers and evaluated their presence in circulating cell-free DNA (cfDNA). Nearly 2.5% of cfDNA in the plasma of healthy individuals originates from VECs. Sepsis, graft versus host disease, and cardiac catheterization are associated with elevated levels of VEC-derived cfDNA, indicative of vascular damage. Lung-specific VEC cfDNA is selectively elevated in patients with chronic obstructive pulmonary disease (COPD) or lung cancer, revealing tissue-specific vascular turnover. VEC cfDNA biomarkers inform vascular dynamics in health and disease, potentially contributing to early diagnosis and monitoring of pathologies, and assessment of drug activity. This work was supported by the Beutler Research Program, Helmsley Charitable Trust, JDRF, Grail and the DON Foundation (to Y.D.). Y.D holds the Walter& Greta Stiel Chair in heart studies. B.G., R.S., J.M., D.N., T.K., and Y.D. filed patents on cfDNA analysis.

Acute delirium as a form of presentation of a thalamic hemorrhagic stroke

Delirium is a frequent cause of decompensation in the elderly, especially with higher prevalence in highly dependent patients, in advanced ages and senile dementia. It is important to always look for the principal cause before treating only the symptom. This case describes a 79-year-old woman with an episode of agitation and disorientation lasting several days, underestimated by its mild nature, but which ends up being a thalamic hemorrhagic stroke. Hemorrhagic stroke is a less common pathology than ischemic stroke but with higher morbidity and mortality. Specifically focused on the thalamus produces behavioral and sensory alterations that can be confused with multiple pathologies. Early identification and approach influence recovery and the sequelae that are being worked with different physiotherapeutic therapies.

MitoEVs: A new player in multiple disease pathology and treatment.

Mitochondrial damage plays vital roles in the pathology of many diseases, such as cancers, neurodegenerative diseases, aging, metabolic diseases and many types of organ injury. However, the regulatory mechanism of mitochondrial functions among different cells or organs in vivo is still unclear, and efficient therapies for attenuating mitochondrial damage are urgently needed. Extracellular vesicles (EVs) are cell-derived nanovesicles that can deliver bioactive cargoes among cells or organs. Interestingly, recent evidence shows that diverse mitochondrial contents are enriched in certain EV subpopulations, and such mitoEVs can deliver mitochondrial components to affect the functions of recipient cells under different conditions, which has emerged as a hot topic in this field. However, the overview and many essential questions with respect to this event remain elusive. In this review, we provide a global view of mitoEVs biology and mainly focus on the detailed sorting mechanisms, functional mitochondrial contents, and diverse biological effects of mitoEVs. We also discuss the pathogenic or therapeutic roles of mitoEVs in different diseases and highlight their potential as disease biomarkers or therapies in clinical translation. This review will provide insights into the pathology and drug development for various mitochondrial injury-related diseases.

Patients' Perceived Importance of Medication and Adherence in Polypharmacy, a Quantitative, Cross-Sectional Study Using a Questionnaire Administered in Three Doctors' Private Practices in France.

Among the determinants of nonadherence, polypharmacy (common in people with multiple pathologies and especially in elderly patients), plays a major role. In patients who are subject to polypharmacy involving different classes of medications, the first aim is to assess the impact of medication importance given by patients on (i) medication adherence and (ii) the respective effect of intentionality and habit in medication importance and medication adherence. The second objective is to compare the importance given to medication and adherence in the different therapeutic classes. Patients taking 5-10 different medications for at least 1 month were included in a cross-sectional survey in three private practices in one region in France. This study included 130 patients (59.2 % female) with 851 medications in total. The mean ± standard deviation (SD) age was 70.5 ± 12.2 years. The mean ± SD of medications taken was 6.9 ± 1.7. Treatment adherence had a strong positive correlation with the patient-perceived medication importance (p < 0.001). Counter-intuitively, taking a large number of medications (≥7) was associated with being fully adherent (p = 0.02). A high intentional nonadherence score was negatively associated with high medication importance (p = 0.003). Furthermore, patient-perceived medication importance was positively associated with taking treatment by habit (p = 0.03). Overall nonadherence more strongly correlated with unintentional nonadherence (p < 0.001) than with intentional nonadherence (p = 0.02). Compared to the antihypertensive class, a decrease in adherence by medication was observed in psychoanaleptics (p < 0.0001) and drugs used in diabetes class (p = 0.002), and a decrease in importance in lipid-modifying agents class (p = 0.001) and psychoanaleptics (p < 0.0001). The perception of the importance of a medicine is associated with the place of intentionality and habit in patient adherence. Therefore, explaining the importance of a medicine should become an important part of patient education.

IMC-Denoise: a content aware denoising pipeline to enhance Imaging Mass Cytometry

Imaging Mass Cytometry (IMC) is an emerging multiplexed imaging technology for analyzing complex microenvironments using more than 40 molecularly-specific channels. However, this modality has unique data processing requirements, particularly for patient tissue specimens where signal-to-noise ratios for markers can be low, despite optimization, and pixel intensity artifacts can deteriorate image quality and downstream analysis. Here we demonstrate an automated content-aware pipeline, IMC-Denoise, to restore IMC images deploying a differential intensity map-based restoration (DIMR) algorithm for removing hot pixels and a self-supervised deep learning algorithm for shot noise image filtering (DeepSNiF). IMC-Denoise outperforms existing methods for adaptive hot pixel and background noise removal, with significant image quality improvement in modeled data and datasets from multiple pathologies. This includes in technically challenging human bone marrow; we achieve noise level reduction of 87% for a 5.6-fold higher contrast-to-noise ratio, and more accurate background noise removal with approximately 2 × improved F1 score. Our approach enhances manual gating and automated phenotyping with cell-scale downstream analyses. Verified by manual annotations, spatial and density analysis for targeted cell groups reveal subtle but significant differences of cell populations in diseased bone marrow. We anticipate that IMC-Denoise will provide similar benefits across mass cytometric applications to more deeply characterize complex tissue microenvironments.