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Diagnostic Cytopathology Feb 2023Hepatocellular carcinoma (HCC) accounts for most primary tumors of the liver. Although bone metastasis does not occur in a high percentage of patients, bone metastasis...
Hepatocellular carcinoma (HCC) accounts for most primary tumors of the liver. Although bone metastasis does not occur in a high percentage of patients, bone metastasis is often found first, which leads to the diagnosis of HCC. In this report, we describe a case of bone metastasis from HCC in which bone lesions were detected incidentally, and in which a cytological diagnosis was difficult to make. The patient was a 78-year-old man with a history of renal dysfunction after orthopedic surgery. He underwent a thorough examination after a bone tumor was incidentally found on abdominal CT. Plasmacytoma was suspected. Fine needle aspiration cytology revealed irregular clusters of medium-to-large atypical epithelioid polygonal cells with relatively abundant eosinophilic, somewhat granular cytoplasm, and indistinct cell borders, which led to a diagnosis of malignancy. Histologically and immunohistochemically, the tumor was diagnosed as bone metastasis of HCC. Re-examination of the cytological specimen revealed characteristic Mallory hyaline bodies (MHBs). Immunohistochemistry using a cell transfer method revealed that they were positive for low molecular weight cytokeratin, Cam5.2, in a densely granular fashion. In this case, the cytological diagnosis of HCC was difficult to make due to the unclear cytoplasmic borders and absence of bile pigment. However, the identification of MHBs can potentially guide me to the correct cytological diagnosis.
Topics: Male; Humans; Aged; Carcinoma, Hepatocellular; Liver Neoplasms; Hyalin; Bone Neoplasms
PubMed: 36345980
DOI: 10.1002/dc.25072 -
Journal of Clinical and Experimental... 2022Excessive alcohol consumption is a global healthcare problem with enormous social, economic, and clinical consequences. While chronic, heavy alcohol consumption causes... (Review)
Review
Excessive alcohol consumption is a global healthcare problem with enormous social, economic, and clinical consequences. While chronic, heavy alcohol consumption causes structural damage and/or disrupts normal organ function in virtually every tissue of the body, the liver sustains the greatest damage. This is primarily because the liver is the first to see alcohol absorbed from the gastrointestinal tract via the portal circulation and second, because the liver is the principal site of ethanol metabolism. Alcohol-induced damage remains one of the most prevalent disorders of the liver and a leading cause of death or transplantation from liver disease. Despite extensive research on the pathophysiology of this disease, there are still no targeted therapies available. Given the multifactorial mechanisms for alcohol-associated liver disease pathogenesis, it is conceivable that a multitherapeutic regimen is needed to treat different stages in the spectrum of this disease.
PubMed: 36340300
DOI: 10.1016/j.jceh.2022.05.004 -
Molecules (Basel, Switzerland) Oct 2022Griseofulvin is an antifungal polyketide metabolite produced mainly by ascomycetes. Since it was commercially introduced in 1959, griseofulvin has been used in treating... (Review)
Review
Griseofulvin is an antifungal polyketide metabolite produced mainly by ascomycetes. Since it was commercially introduced in 1959, griseofulvin has been used in treating dermatophyte infections. This fungistatic has gained increasing interest for multifunctional applications in the last decades due to its potential to disrupt mitosis and cell division in human cancer cells and arrest hepatitis C virus replication. In addition to these inhibitory effects, we and others found griseofulvin may enhance ACE2 function, contribute to vascular vasodilation, and improve capillary blood flow. Furthermore, molecular docking analysis revealed that griseofulvin and its derivatives have good binding potential with SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp), and spike protein receptor-binding domain (RBD), suggesting its inhibitory effects on SARS-CoV-2 entry and viral replication. These findings imply the repurposing potentials of the FDA-approved drug griseofulvin in designing and developing novel therapeutic interventions. In this review, we have summarized the available information from its discovery to recent progress in this growing field. Additionally, explored is the possible mechanism leading to rare hepatitis induced by griseofulvin. We found that griseofulvin and its metabolites, including 6-desmethylgriseofulvin (6-DMG) and 4- desmethylgriseofulvin (4-DMG), have favorable interactions with cytokeratin intermediate filament proteins (K8 and K18), ranging from -3.34 to -5.61 kcal mol. Therefore, they could be responsible for liver injury and Mallory body (MB) formation in hepatocytes of human, mouse, and rat treated with griseofulvin. Moreover, the stronger binding of griseofulvin to K18 in rodents than in human may explain the observed difference in the severity of hepatitis between rodents and human.
Topics: Mice; Humans; Rats; Animals; Griseofulvin; Antifungal Agents; SARS-CoV-2; Angiotensin-Converting Enzyme 2; Molecular Docking Simulation; Spike Glycoprotein, Coronavirus; COVID-19; Keratins; RNA-Dependent RNA Polymerase; Polyketides
PubMed: 36296627
DOI: 10.3390/molecules27207034 -
Diseases of the Esophagus : Official... Mar 2023Transcervical esophagectomy allows for esophagectomy through transcervical access and bypasses the thoracic cavity, thereby eliminating single lung ventilation. A... (Review)
Review
BACKGROUND
Transcervical esophagectomy allows for esophagectomy through transcervical access and bypasses the thoracic cavity, thereby eliminating single lung ventilation. A challenging surgical approach demands thorough understanding of the encountered anatomy. This study aims to provide a comprehensive overview of surgical anatomy encountered during the (robot-assisted) minimally invasive transcervical esophagectomy (RACE and MICE).
METHODS
To assess the surgical anatomy of the lower neck and mediastinum, MR images were made of a body donor after, which it was sliced at 24-μm intervals with a cryomacrotome. Images were made every 3 slices resulting in 3.200 images of which a digital 3D multiplanar reconstruction was made. For macroscopic verification, microscopic slices were made and stained every 5 mm (Mallory-Cason). Schematic drawings were made of the 3D reconstruction to demonstrate the course of essential anatomical structures in the operation field and identify anatomical landmarks.
RESULTS
Surgical anatomy 'boxes' of three levels (superior thoracic aperture, upper mediastinum, subcarinal) were created. Four landmarks were identified: (i) the course of the thoracic duct in the mediastinum; (ii) the course of the left recurrent laryngeal nerve; (iii) the crossing of the azygos vein right and dorsal of the esophagus; and (iv) the position of the aortic arch, the pulmonary arteries, and veins.
CONCLUSIONS
The presented 3D reconstruction of unmanipulated human anatomy and schematic 3D 'boxes' provide a comprehensive overview of the surgical anatomy during the RACE or MICE. Our findings provide a useful tool to aid surgeons in learning the complex anatomy of the mediastinum and the exploration of new surgical approaches such as the RACE or MICE.
Topics: Humans; Esophagectomy; Lymph Node Excision; Robotics; Esophageal Neoplasms
PubMed: 36222066
DOI: 10.1093/dote/doac072 -
Annals of Eye Science Mar 2022In the early days of deciphering the injured neuronal tissues led to the realization that contrast is necessary to discern the parts of the recovering tissues from the...
In the early days of deciphering the injured neuronal tissues led to the realization that contrast is necessary to discern the parts of the recovering tissues from the damaged ones. Early attempts relied on available (and often naturally occurring) staining substances. Incidentally, the active ingredients of most of them were small molecules. With the advent of time, the knowledge of chemistry helped identify compounds and conditions for staining. The staining reagents were even found to enhance the visibility of the organelles. Silver impregnation identification of Golgi bodies was discovered in owl optic nerve. Staining reagents since the late 1800s were widely used across all disciplines and for nerve tissue and became a key contributor to advancement in nerve-related research. The use of these reagents provided insight into the organization of the neuronal tissues and helped distinguish nerve degeneration from regeneration. The neuronal staining reagents have played a fundamental role in the clinical research facilitating the identification of biological mechanisms underlying eye and neuropsychiatric diseases. We found a lack of systematic description of all staining reagents, whether they had been used historically or currently used. There is a lack of readily available information for optimal staining of different neuronal tissues for a given purpose. We present here a grouping of the reagents based on their target location: (I) the central nervous system (CNS), (II) the peripheral nervous system (PNS), or (III) both. The biochemical reactions of most of the staining reagents is based on acidic or basic pH and specific reaction partners such as organelle or biomolecules that exists within the given tissue type. We present here a summary of the chemical composition, optimal staining condition, use for given neuronal tissue and, where possible, historic usage. Several biomolecules such as lipids and metabolites lack specific antibodies. Despite being non-specific the reagents enhance contrast and provide corroboration about the microenvironment. In future, these reagents in combination with emerging techniques such as imaging mass spectrometry and kinetic histochemistry will validate or expand our understanding of localization of molecules within tissues or cells that are important for ophthalmology and vision science.
PubMed: 36177475
DOI: 10.21037/aes-21-31 -
Clinical Breast Cancer Dec 2022Microporous polysaccharide particles (MPP, proprietary name "Arista AH"), derived from purified plant starch, are used to augment hemostasis at surgery. The effect of...
BACKGROUND
Microporous polysaccharide particles (MPP, proprietary name "Arista AH"), derived from purified plant starch, are used to augment hemostasis at surgery. The effect of MPP regarding short-term complications after mastectomy remains an area of ongoing investigation.
PATIENTS AND METHODS
A single-institution, retrospective chart review of patients undergoing unilateral mastectomy without reconstruction from January 2019 to 2021 was performed. Primary endpoints included antibiotic prescription, seroma or abscess drainage, readmission, wound dehiscence, and time to drain removal within 30 days of initial surgery. Wilcoxon rank sum test or Student t test was used for group comparisons for continuous variables; Chi-square test or Fisher exact test was used to evaluate the associations among categorical variables.
RESULTS
One hundred ninety patients were included; 119 received MPP and 71 did not. There was no difference in antibiotic prescription, infection drainage, hematoma, readmission, dehiscence, or time to drain removal with regards to MPP use. MPP treated patients were older (65.8 years vs. 59.1, P < .001) and had lower albumin levels (4.1 g/dL vs. 4.3, P = .025). Patients who underwent abscess drainage had higher body mass index ( mean 36.1 vs. 30.1 P = .036). Patients requiring seroma drainage were more likely to be diabetic (12.8% vs. 4%, P = .035) and to have been treated with lymphovenous anastomosis (LVA, 15.6% vs. 3.8%, P = .009). Patients who had LVA were significantly less likely to receive MPP when compared to other groups (3.1% vs. 74.7% P < .001).
CONCLUSION
Consider utilizing MPP in patients at higher risk of seroma, such as those undergoing axillary surgery including LVA.
Topics: Humans; Female; Mastectomy; Seroma; Retrospective Studies; Abscess; Breast Neoplasms; Drainage; Postoperative Complications; Polysaccharides; Anti-Bacterial Agents
PubMed: 36055918
DOI: 10.1016/j.clbc.2022.07.015 -
Neuromuscular Disorders : NMD Aug 2022LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related myopathy (SELENON-RM) are rare neuromuscular diseases caused by mutations in the LAMA2 and SELENON... (Review)
Review
LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related myopathy (SELENON-RM) are rare neuromuscular diseases caused by mutations in the LAMA2 and SELENON (SEPN1) gene, respectively. Systematic reviews on cardiac features in both neuromuscular diseases are lacking. This scoping review aims to elucidate the cardiac involvement in LAMA2-MD or SELENON-RM. Three electronic databases (PubMed, Embase and Cochrane) were searched. All studies, case reports and case series with information on cardiac features in LAMA2-MD or SELENON-RM patients were included. Study selection and data extraction were performed by two independent reviewers. 31 Articles on LAMA2-MD and 17 articles on SELENON-RM met the inclusion criteria, resulting in the inclusion of 131 LAMA2-MD and 192 SELENON-RM cases. In 41% of LAMA2-RM cases, a cardiac abnormality was present. Left ventricular systolic dysfunction and arrhythmia were most frequently described. In 15% of SELENON-RM cases, a cardiac abnormality was reported, of which pulmonary hypertension, including right ventricular dysfunction secondary to pulmonary failure, was most prevalent. We conclude that in LAMA2-MD primary left ventricular dysfunction and in SELENON-RM secondary right ventricular dysfunction are frequently reported. Optimal cardiorespiratory surveillance by screening of asymptomatic patients every two years with ECG, Holter and echocardiography is necessary for early detection and/or treatment of cardiac manifestations.
Topics: Humans; Laminin; Mallory Bodies; Muscular Diseases; Muscular Dystrophies; Mutation; Scoliosis; Ventricular Dysfunction, Right
PubMed: 35868898
DOI: 10.1016/j.nmd.2022.06.004 -
Military Medicine Aug 2023After over 20 years of war in the Middle East, orthopedic injuries have been among the most prevalent combat-related injuries, accounting for 14% of all surgical...
INTRODUCTION
After over 20 years of war in the Middle East, orthopedic injuries have been among the most prevalent combat-related injuries, accounting for 14% of all surgical procedures at Role 2/3 (R2/R3) facilities according to the DoD Trauma Registry. To further delineate the role of the deployed orthopedic surgeon on the modern battlefield, a retrospective review was performed highlighting both quantitative and qualitative analysis factors associated with orthopedic surgical care during the war in the Middle East.
METHODS
A retrospective review was conducted of orthopedic surgeons in the Middle East from 2001 to 2021. A comprehensive literature search was conducted using the PubMed and Embase databases using a two-reviewer strategy. Articles were compiled and reviewed using Covidence. Inclusion criteria included journal articles focusing on orthopedic injuries sustained during the Global War on Terror (GWoT) in an adult U.S. Military population. In the event of a conflict, a third author would determine the relevance of the article. For the remaining articles, a full-text review was conducted to extract relevant predetermined quantitative data, and the Delphi consensus method was then utilized to highlight relevant qualitative themes.
RESULTS
The initial search yielded 1,226 potentially relevant articles. In all, 40 studies ultimately met the eligibility criteria. With the consultation of previously deployed orthopedic surgeons at the Walter Reed National Military Medical Center, a retrospective thematic analysis of the 40 studies revealed five themes encompassing the orthopedic surgeons experience throughout GWoT. These themes include unique mechanisms of orthopedic injury compared to previous war injuries due to novel weaponry, differences in interventions depending on R2 versus R3 locations, differences in injuries from those seen in civilian settings, the maintained emphasis on humanitarian aspect of an orthopedic surgeon's mission, and lastly relation of pre-deployment training to perceived deployed success of the orthopedic surgeons. From this extensive review, we found that explosive mechanisms of injury were greatly increased when compared to previous conflicts and were the etiology for the majority of orthopedic injuries sustained. With the increase of complex explosive injuries in the setting of improved body armor and overall survival, R2/3 facilities showed an increased demand for orthopedic intervention including debridement, amputations, and external fixation. Combat injuries sustained during the GWoT differ in the complications, management, and complexity when compared to civilian trauma. "Humanitarian" cases made up a significant number of operative cases for the deployed orthopedic surgeon. Lastly, heterogeneous training opportunities were available prior to deployment (fellowship, combat extremity surgical courses, and dedicated pre-deployment training), and the most commonly identified useful training was learning additional soft-tissue coverage techniques.
CONCLUSION
These major themes indicate an emphasis on pre-deployment training and the strategic positioning of orthopedic surgeons to reflect the changing landscape of musculoskeletal trauma care. Moving forward, these authors recommend analyzing the comfort and perceived capability of orthopedic surgeons in these unique military environments to best prepare for a changing operational format and the possibility of future peer-peer conflicts that will likely lead to a lack of medical evacuation and prolonged field care.
Topics: Adult; Humans; Orthopedic Surgeons; Retrospective Studies; Afghan Campaign 2001-; Orthopedics; Amputation, Surgical; Military Medicine
PubMed: 35862000
DOI: 10.1093/milmed/usac219 -
Experimental and Molecular Pathology Aug 2022Mallory-Denk bodies (MDBs) consist of intracellular aggregates of misfolded proteins in ballooned hepatocytes and serve as important markers of progression in certain...
Mallory-Denk bodies (MDBs) consist of intracellular aggregates of misfolded proteins in ballooned hepatocytes and serve as important markers of progression in certain liver diseases. Resident hepatic macrophage-mediated inflammation influences the development of chronic liver diseases and cancer. Here, the first systematic study of macrophages heterogeneity in mice was conducted to illustrate the pathogenesis of MDB formation using single-nucleus RNA sequencing (snRNA-seq). Furthermore, we provided transcriptional profiles of macrophages obtained from the fractionation of mouse liver tissues following chronic injury. We equally identified seven discrete macrophage subpopulations, each involved in specific cellular activated pathways such as basal metabolism, immune regulation, angiogenesis, and cell cycle regulation. Among these, a specific macrophage cluster (Cluster4), a subpopulation specifically expressing genes that regulate cell division and the cell cycle, was identified. Interestingly, we found that CCR2 was significantly induced in Cluster2, thereby inducing monocytes to migrate to macrophages to promote MDB pathogenesis. Thus, our study is the first to demonstrate the heterogeneity of macrophages associated with liver MDB formation in mice through single-cell resolution. This serves as the basis for further insights into the pathogenesis of liver MDB formation and molecular mechanisms of chronic liver disease progression.
Topics: Animals; Hepatocytes; Liver; Liver Diseases; Macrophages; Mallory Bodies; Mice; Transcriptome
PubMed: 35850229
DOI: 10.1016/j.yexmp.2022.104811 -
American Journal of Public Health Jun 2022Researchers are increasingly recognizing the importance of studying and addressing intersectional stigma within the field of HIV. Yet, researchers have, arguably,...
Researchers are increasingly recognizing the importance of studying and addressing intersectional stigma within the field of HIV. Yet, researchers have, arguably, struggled to operationalize intersectional stigma. To ensure that future research and methodological innovation is guided by frameworks from which this area of inquiry has arisen, we propose a series of core elements for future HIV-related intersectional stigma research. These core elements include multidimensional, multilevel, multidirectional, and action-oriented methods that sharpen focus on, and aim to transform, interlocking and reinforcing systems of oppression. We further identify opportunities for advancing HIV-related intersectional stigma research, including reducing barriers to and strengthening investments in resources, building capacity to engage in research and implementation of interventions, and creating meaningful pathways for HIV-related intersectional stigma research to produce structural change. Ultimately, the expected payoff for incorporating these core elements is a body of HIV-related intersectional stigma research that is both better aligned with the transformative potential of intersectionality and better positioned to achieve the goals of Ending the HIV Epidemic in the United States and globally. (. 2022;112(S4):S413-S419. https://doi.org/10.2105/AJPH.2021.306710).
Topics: HIV Infections; Humans; Mental Disorders; Social Stigma; United States
PubMed: 35763749
DOI: 10.2105/AJPH.2021.306710