Histopathological Research Articles

Can smartphone cameras help with diagnostic adequacy in renal biopsy?

Background In this prospective study, we evaluated whether a sufficient number of glomeruli were achieved using the 8× magnification of smartphone cameras. Purpose To increase the percutaneous ultrasound-guided renal biopsy (PURB) diagnostic value with a method that has not been tried before and reduce the need for repetition of the procedure. Material and Methods A total of 39 adult patients who underwent PURB were included in our study. After the PURB was applied to the patients, the biopsy specimen was placed on the previously prepared sterile gauze. At this stage, 8× magnification photos were taken of the biopsy samples using the smartphone camera. The glomeruli in the photograph were counted and recorded and compared with the number of glomeruli seen at the end of the histopathological examination. Results The mean number of glomeruli in the evaluated samples was counted as 6 ± 2.2 (range = 1–10) in the 8× magnification photograph. The mean number of glomeruli detected in the histopathological examination of these samples was 11 ± 5.7 (range = 2–30). A pathological glomeruli count of 10 was associated with more than five brown spots in the 8× magnification photograph (area under the curve = 0.977, P=0.0001). Conclusion To obtain more than 10 glomeruli in a PURB specimen, five or more brownish-red dots should be counted on the 8x magnification photograph. Using smartphones as an alternative tool for evaluating renal biopsy tissue adequacy can be practical and advantageous in terms of time and labor.

Nodular vasculitis – Retrospective study of an uncommon disease in a non-tuberculosis endemic country with focus on treatment modalities and efficacy

Introduction Nodular vasculitis (NV) is a rare form of panniculitis primarily affecting middle-aged females, presenting as painful, sometimes ulcerated nodules on the dorsal lower legs. Erythema induratum Bazin (EIB) is a form of NV and is considered a manifestation of cutaneous tuberculin hypersensitivity. This retrospective study aims to analyze demographics, clinicopathological findings, laboratory results, and treatment outcomes of NV in a non-TB endemic country. Methods: Data of NV patients were extracted from the electronic hospital database of the University Hospital Zurich. Patients were included only if histopathologically confirmed diagnosis of NV and sufficient information on demographics, treatment, and follow-up was available. Results: We conducted a 20-year retrospective study , including 62 patients with NV. The most common site of involvement was the lower extremities. Disease duration varyied from several months to over 20 years. Histopathological examination revealed lobular panniculitis, with or without vasculitis, and granuloma formation. Tuberculosis association was assessed through the QuantiFERON test and Mycobacteria PCR, showing positive results in 22 or 37 (59%) tested cases and in 2 out of 27 cases (7.4%), respectively. . Comorbidities were found in over half of the patients. Treatment modalities included topical corticosteroids, antitubercular therapy, systemic steroids, and potassium iodide. Almost 50% of all patients experienced relapses despite treatment. Conclusion: Topical steroids, antitubercular therapy, systemic steroids, and potassium iodide showed similar response rates. Tuberculostatic therapy upon detecting latent TB is recommended. Considering the high recurrence rate and potential side effects of systemic therapies, we recommend first-line treatment with potent topical steroids and compression stockings.

Efficacy of Autofluorescence in Detection of Tobacco-associated Oral Mucosal Lesions - A Systematic Review

Abstract Background: This study was conducted with the aim to systematically review the efficacy of autofluorescence in the detection of tobacco-associated oral mucosal lesions. Objectives and Data Sources: Clinical studies with patients that focused on the autofluorescence method in the detection, visualisation, or management of tobacco-associated oral mucosal lesions were included in the literature search across bibliographic databases. Results: Autofluorescence visualisation showed positive results, with high sensitivity scores when compared with the gold standard of histopathology in the clinical evaluation of common tobacco-associated oral mucosal lesions. However, the low specificity values indicate its limited ability to distinguish between dysplasia and other benign conditions. Conclusions and Implications: This review provides promising evidence for the application of autofluorescence in the detection of tobacco-associated oral mucosal lesions where autofluorescence is used in conjunction with conventional examination with the gold standard of histopathological examination. Registration number: PROSPERO 2023 CRD42023442292.

Malignant Transformation of Recurrent Benign Phyllodes Tumor: A Case Report and comprehensive review of literature

Introduction: Phyllodes tumors (PTs) of the breast are rare fibroepithelial neoplasms, accounting for less than 1% of all breast tumors. The World Health Organization (WHO) classifies PTs into benign, borderline, or malignant categories based on histological features. While benign PTs generally have a favorable prognosis, they carry a risk of transformation into malignant variants, particularly in cases of recurrence. Case Presentation: A 33-year-old female presented with a recurrent benign PT, previously treated with lumpectomy on two occasions. Recent imaging suggested possible malignant transformation, and histopathological examination confirmed a malignant PT. Discussion: This case highlights the crucial role of imaging in the early detection of malignant transformation in PTs. Surgical management strategies are discussed, with an emphasis on the potential for recurrent benign tumors to progress to malignancy. Conclusion: Regular imaging and close follow-up are essential for early detection of malignant transformation in recurrent PTs, guiding timely and appropriate surgical intervention.

Sumac liposomes/mesenchymal stem cells fight methotrexate-induced nephrotoxicity in rats via regulating Nrf-2/Keap-1/HO-1 and apoptotic signaling pathways.

Methotrexate (MTX) is commonly employed in cancer treatment, but its clinical use is restricted due to the MTX-associated renal injury. This study investigates the combined potential of Rhus coriaria (sumac) and bone marrow mesenchymal stem cells (BMMSCs) against MTX-induced nephrotoxicity in rats. The high-resolution-liquid chromatography-mass spectrometry (HR-LC-MS) of sumac extract tentatively identified 22 phytochemicals, mostly flavonoids, anthocyanins, and steroids. Preparation of sumac liposomes attained a suitable particle size of 3041.33 ± 339.42 nm, a polydispersity index of 0.208 ± 0.086, and an encapsulation efficiency of 84.92 ± 3.47%. Rat BMMSCs were injected into the tail vein of the experimental rats (0.5 × 106 cells, intravenous [iv]) of seven treated groups. The experimental design relies on either pre- or posttreatment of rats with intraperitoneal (IP) sumac liposomes (SL) (200 mg/kg, daily with a dose of MTX (300 µg/kg/14 days). The histopathological examination and serum analysis of creatinine and urea revealed good results, besides regulating levels of oxidative stress and inflammatory markers. Additionally, a significant decrease in the gene expression levels of B-Cell Lymphoma 2 (Bcl-2) and caspases-3 and -9, a remarkable increase in the Bcl-2 Associated X-Protein (Bax), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme-oxygenase 1 expression, and a downregulation of Kelch-like ECH-associated protein 1 (Keap1). Collectively, the coadministration of SL with BMMSCs might be a potent therapeutic strategy for attenuation of MTX-induced renal damage. The network pharmacology analysis identified the involved key hub genes as KEAP1, Nrf2, HMOX1, mitogen-activated protein kinase (MAPK1), nuclear factor-kappa B (NF-KB), interleukin-1 beta (IL-1B), and caspase-3. The docking results revealed strong binding affinities of 7-O-methyl-cyanidin-3-O-(2″-galloyl)-galactoside with Keap1 and amentoflavone with MAPK. These insights pave the way for future experimental validation and therapeutic development of sumac-based phytoconstituents against MTX-induced nephrotoxicity.

Clinical and pathologic characteristics of inflamed juvenile conjunctival nevus and its treatment with immunosuppressant eye drops.

To clarify the clinical and pathologic findings of 7 patients with inflamed juvenile conjunctival nevus (IJCN) treated with tacrolimus. Retrospective study. The medical records of 7 male patients diagnosed with IJCN between February 2007 and October 2022 at the Kansai Medical University Hospital and Ideta Eye Hospital were retrospectively reviewed. The patients' mean age was 11.3 (8-20) years, and the average follow-up period was 18 months. The patients underwent anterior segment optical coherence tomography (AS-OCT) and anterior segment optical coherence tomography angiography (AS-OCTA). All the patients were treated with steroids or immunosuppressant eye drops, or both. Histopathologic examinations were performed on specimens resected from 2 patients. The clinical characteristics of IJCN were as follows: (1) presence of cysts within a pigmented conjunctival mass, (2) tumor accompanied by feeder vessels, and (3) predominantly found in boys with allergic diseases. AS-OCT and AS-OCTA revealed the presence of a cystic structure with poor vascular signals within it and numerous vessels distributed on the sclera underlying the lesion. Immunosuppressant eye drops relieved the congestion, diminished the inflow vessels, and induced shrinkage of the cysts in all the patients. Histopathologic examinations revealed infiltration of inflammatory cells such as lymphocytes and macrophages and low proliferative activity of melanocytes with no division pattern. This study clarified the clinical and histologic characteristics of IJCN. Noninvasive AS-OCT and AS-OCTA might be useful for diagnosing IJCN. The histopathologic findings of this study indicate that immunosuppressive and antiallergic agents can effectively bring about disease remission.

Machine learning prediction of brain metastasis invasion pattern on brain MRI scans

Abstract Background Brain metastasis invasion pattern (BMIP) is an emerging biomarker associated with recurrence-free and overall survival in patients, and differential response to therapy in preclinical models. Currently, BMIP can only be determined from the histopathological examination of surgical specimens, precluding its use as a biomarker prior to therapy initiation. The aim of this study was to investigate the potential of machine learning (ML) approaches to develop a non-invasive magnetic resonance imaging (MRI)-based biomarker for BMIP determination. Methods From an initial cohort of 329 patients, a subset of 132 patients met inclusion criteria for this retrospective study. We evaluated the ability of an expert neuroradiologist to reliably predict BMIP. Thereafter, the dataset was randomly divided into training/validation (80% of cases) and test subsets (20% of cases). Ground truth for BMIP was histopathologic evaluation of resected specimens. Following MRI sequence co-registration, advanced feature extraction techniques deriving hand-crafted radiomic features with traditional ML classifiers and convolution-based deep learning (CDL) models were trained and evaluated. Different ML approaches were used individually or using ensembling techniques to determine the model with the best performance for BMIP prediction. Results Expert evaluation of brain MRI scans could not reliably predict BMIP, with an accuracy of 44-59% depending on the semantic feature used. Among the different ML and CDL models evaluated, the best performing model achieved an accuracy of 85% and an F1-score of 90%. Conclusion ML approaches can effectively predict BMIP, representing a non-invasive MRI-based approach to guide management of patients with brain metastases.

Effectiveness of autologous fat graft and methylprednisolone as single and combination therapy in the prevention of epidural fibrosis

Objectives: Epidural fibrosis is a common complication following laminectomy, contributing to failed back surgery syndrome characterized by back pain and radiculopathy. Despite ongoing research, no consensus exists on the best method to prevent epidural fibrosis. This animal study aimed to compare the effectiveness of autologous fat grafts and methylprednisolone as single and combination therapies in preventing epidural fibrosis. Methods: Four groups of rats, each containing 7, underwent different treatments post-lumbar laminectomy: A control group, a group receiving methylprednisolone in the epidural space, a group receiving an autologous fat graft, and a group receiving both methylprednisolone and an autologous fat graft. After 6 weeks, the formation of epidural fibrosis was evaluated through histopathological examination based on the classification. The degree of epidural fibrosis was analyzed. Results: The autologous fat graft group exhibited the lowest degree of fibrosis (Grade 1). Comparisons between this group and the others showed a significant difference (P < 0.05). No significant difference was observed between the control, methylprednisolone, and combination groups (P > 0.05). Conclusion: The study demonstrated a significant reduction in histological epidural fibrosis using autologous fat grafts compared to methylprednisolone and their combination in animal models. Histological analysis indicated that autologous fat grafts resulted in a lower degree of fibrosis following laminectomy.

Vascular hamartoma in horse limbs: presentation, diagnosis, and treatment of two case studies.

Vascular hamartoma is an abnormal development of endothelial tissue that rarely affects horses. Histopathological examination remains the gold standard for definitive diagnosis, yet the presence of abnormal vascular structures must be carefully differentiated from other vascular anomalies and neoplasms. This report describes two cases of vascular proliferation affecting the skin on the lateral side over the left tarsus and the dorsolateral region over the fetlock joint of two fillies. The clinical history, presentation, and radiographic and sonographic findings in both patients suggested a neoplasm of unknown origin. Surgical excision of the mass was successfully performed in both patients. In one patient, a second surgery was performed six months after the first surgery because of the recurrence of the mass. Histopathological examination revealed a disorganized proliferation of well-differentiated, tortuous, and varied-sized blood vessels hemmed in myxoid tissue with abundant fibrocollagenous bands. Immunohistochemical examination of the endothelium markers factor VIII and ERG revealed positive staining of the mass samples in both cases, confirming their vascular origin. The combination of these markers was effective, providing a reliable option for differentiating vascular proliferation in horses. To the best of the author's knowledge, this is the first report applying the ERG endothelial marker to horse vascular malformations.

The effect of silymarin on ischemia-reperfusion injury in skeletal muscles of rats silymarin and ischemia-reperfusion injury

Aim: Although the precise process is not entirely elucidated, it is well-known that oxidative stress mediators contribute to ischemia-reperfusion (I/R) injury. The impact of silymarin on I/R injury in many different tissues has been examined. For this purpose, we planned to see the effect of silymarin on muscle tissue in rats subjected to lower extremity I/R injury. Material and Methods: We used 18 male Wistar albino rats weighing 225-275 g. Each of the three groups of rats [Control (C), Ischemia-Reperfusion (I/R), and Silymarin-Ischemia/Reperfusion (S-I/R)] consisted of six rats. Silymarin was administered intraperitoneally 30 minutes before the procedure. (100 mg/kg-1) In Group I/R, the infrarenal abdominal aorta was clamped with a microvascular clamp. The clamp was removed after 120 minutes, and reperfusion was achieved for the next 120 minutes. At the end of the reperfusion period, muscle tissue samples were collected, and Malondialdehyde (MDA), catalase (CAT) enzyme activity levels and histopathological parameters were compared. Results: In the histopathological examination, no degeneration was observed in the muscle fibers in the Group C, while findings of striated muscle damage such as muscle atrophy/hypertrophy, muscle degeneration/congestion, internalization of the muscle nucleus/oval/central nucleus, fragmentation/hyalinization and leukocyte cell infiltration were seen in the Group I/R. In Group S-I/R, muscle atrophy /hypertrophy, internalization of the muscle nucleus/oval/central nucleus, fragmentation/hyalinization, and leukocyte cell infiltration were observed to improve these damaged areas compared to Group I/R. MDA levels in the Group I/R were significantly higher compared to Group C and S-I/R. The activity of the CAT enzyme was much higher in Group I/R compared to Group C. Conclusion: Our study revealed that 100 mg/kg-1 silymarin administered by intraperitoneal injection 30 minutes before ischemia effectively decreased lipid peroxidation, oxidative stress, and the injury caused by I/R in muscle histology in rats.

Clinico-dermoscopic and Histopathological Evaluation of Benign Skin, Soft Tissue and Appendageal Tumours of Skin: A Cross-sectional Study from a Tertiary Care Hospital

Abstract Background: Benign skin, soft tissue and appendageal tumours of skin are one of the most frequently encountered skin disorders. An organised systematic approach along with dermoscopic and histopathological examination can aid in the diagnosis of these diverse disorders. Objective: To evaluate clinico-dermoscopic and histopathological findings of benign skin, soft tissue and appendageal tumours of skin in patients attending a tertiary care hospital. Methods: Cross-sectional hospital-based study where patients of all age groups irrespective of gender suspected of having benign skin, soft tissue and appendageal tumours were enrolled. Clinical, dermoscopic and histopathological findings were recorded and the agreements between them were evaluated using the Cohenʼs Kappa coefficient. Results: The study included a total of 415 patients with a mean age of 37.9 ± 15.59 years and a male to female ratio of 1:1.3. The mean duration of the disease was 4.3 ± 2.14 years. Soft tissue tumours were the commonest (60%), followed by benign skin tumours (24.3%) and benign appendageal tumours (17.1%). A good agreement between dermoscopic and clinical diagnosis was found (Cohenʼs Kappa = 0.879) and between dermoscopic and histopathological diagnosis was also found (Cohenʼs Kappa = 0.789). Conclusion: This study infers that benign tumours of the skin include a heterogeneous group of skin disorders affecting a heterogeneous population. Dermoscopy improved the diagnostic accuracy of this large group of skin disorders and reduced the number of unnecessary excisions; however, histopathology remains the benchmark diagnostic tool to differentiate these tumours from other benign tumours and their malignant counterparts.

First Report of Bacterial Kidney Disease (BKD) Caused by Renibacterium salmoninarum in Chum Salmon (Oncorhynchus keta) Farmed in South Korea

In 2021, a prominent increase in mortality was observed in juvenile and subadult cultured chum salmon (Oncorhynchus keta) on a mariculture farm in Jeollanam-do Province, South Korea. The affected fish displayed distinct symptoms: pale gills, petechial hemorrhages in the muscles, and white nodules on the kidneys. Infectious pancreatic necrosis virus (IPNV) was cultured from some fish samples using fish cell lines. Bacteria were isolated from various fish tissues using kidney disease medium-two (KDM-2) culture medium. By detecting and sequencing the 16S rRNA gene using DNA extracted from the kidneys of the infected fish via PCR, the isolated bacteria were identified as Renibacterium salmoninarum. Histopathological examination primarily focused on hematopoietic tissues of kidneys and revealed clear evidence of severe necrosis and granulomatous changes. Additionally, nuclei with peripherally displaced chromatin were abundant in the kidneys of affected fish. These findings suggest that mass mortality of chum salmon was caused by R. salmoninarum, which induced typical bacterial kidney disease (BKD) symptoms, without IPNV infection. This represents the first outbreak of BKD attributed to R. salmoninarum infection in farmed chum salmon in South Korea.

Assessing the Impact of Ghee, Olive Oil and Margarine on Male Rabbit Fertility and Reproductive Hormones.

In the present investigation, the impact of natural ghee, olive oil and synthetic margarine on the fertility parameters of male rabbits was evaluated by examining semen quality, fertility hormones, antioxidant markers, lipid profile, and liver and kidney functions. Eighty male rabbits were randomly allotted into four groups (20 rabbits each, four replicates/group). The basal diet supplemented the control group; the margarine group was fed a 10% margarine diet, the ghee group was fed a 10% ghee diet, and the olive oil group was fed a 10% olive oil diet. In the margarine group, the semen quality parameters, total testosterone levels, free testosterone, luteinizing hormone (LH) and antioxidant enzyme levels as catalase showed a significant reduction compared to other groups. At the same time, they were enhanced in ghee and olive oil groups. A substantial increase of triglyceride (TAG), low-density lipoprotein (LDL) and cholesterol, with a decrease of high-density lipoprotein (HDL) levels, were observed in the margarine group contrasted to ghee and olive oil groups. The ghee and the olive oil-treated group showed strong immunoreactions of androgen, FSH, LH receptors and mild caspase 3 in testicular tissue compared to the margarine-treated group. Finally, histopathological examination of rabbit testicular tissue showed proliferation of basal spermatogenic cells, increased luminal spermatid of seminiferous epithelium, and proliferation of interstitial cells in normal interstitial tissue in the ghee and olive oil treated group. Still, it showed severe vacuolation and necrosis in the basal luminal seminiferous epithelium and congestion of blood vessels in the margarine group. This present study revealed that the health influence of olive oil and ghee is better than margarine on male fertility parameters.

Pathological Examination in Pilonidal Sinus Surgery: Evaluating Necessity and Cost-Effectiveness: A 10-Year Retrospective Analysis.

Malignancy in pilonidal sinus disease (PSD) is rare, with squamous cell carcinoma (SCC) being the most common type. This study aims to assess the incidence of malignancy in PSD and identify risk factors to guide more targeted pathological examination strategies. A retrospective analysis was conducted on 1505 patients who underwent surgical excision of PSD between January 1, 2014, and December 31, 2023. Patients with incomplete or missing histopathological data were excluded, and no imputation methods were used for missing data. All specimens underwent histopathological examination to detect malignancies. Two cases (0.13%) of SCC were identified, both in males aged 50 and 58 years without a history of Crohn's disease, HIV, prior radiation, or other cancers. Significant risk factors for malignancy included age over 40 years (OR 3.2, 95% CI 1.1-9.5) and disease duration over 3 years (OR 2.8, 95% CI 1.0-7.6). Both cases were treated surgically and received adjuvant radiotherapy, with both patients being disease-free at the 2-year follow-up. While malignancy in PSD is rare (0.13%), older age and prolonged disease duration are associated with increased risk. Selective pathological examination based on these risk factors could enhance cost-effectiveness by reducing unnecessary routine examinations.

Appendiceal neurofibroma after resection of multiple gastrointestinal stromal tumors of the small intestine in a patient with neurofibromatosis type 1: a case report.

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant disorder that can affect multiple organs. Although gastrointestinal manifestations, such as neurofibromas and gastrointestinal stromal tumors (GISTs), can occur, appendiceal neurofibromas are extremely rare, with no documented cases of their occurrence following other gastrointestinal lesions. Herein, we report a case of an appendiceal neurofibroma following the resection of multiple small intestinal GISTs. A 68-year-old man with NF1 presented with melena and was diagnosed with anemia due to bleeding from multiple small intestinal GISTs. Laparoscopic three partial resection of the small intestine was performed to control the bleeding. Histopathologic examination revealed the proliferation of spindle cells that are positive for c-kit and Discovered on GIST-1, confirming the diagnosis of GIST. Two years later, a follow-up computed tomography (CT) scan revealed a progressively enlarging mass in the appendix with suspected invasion into the small intestine. Positron emission tomography/CT showed fludeoxyglucose accumulation in the tumor. Therefore, considering the possibility of malignancy, laparoscopic ileocecal resection with lymph node dissection was performed. Postoperatively, melena was observed, but the anemia did not progress and improved with fasting and hemostatic therapy. The patient was eventually discharged on postoperative day 8. Histopathologic examination revealed spindle cell proliferation with positivity for S-100, confirming the diagnosis of neurofibroma. Patients with NF1 can develop a variety of gastrointestinal lesions. Appendiceal neurofibroma can be difficult to diagnose preoperatively and differentiate from malignancy. Hence, surgical resection should be considered.

Blue toe syndrome - systemic cholesterol crystal embolism secondary to cardiovascular procedures: a forensic autopsy report of two cases.

Blue toe syndrome, also referred to as cholesterol crystal embolism is characterized by the distal embolization of cholesterol crystals originating from ruptured atherosclerotic plaques. This condition commonly arises in the context of cardiovascular procedures. Emboli from the thoracoabdominal aorta primarily affect the downstream extremities and intra-abdominal viscera, often resulting in fatal atheroembolic renal failure. Owing to its insidious and delayed onset, antemortem diagnosis of cholesterol crystal embolism is often underrecognized. Two cases of blue toe syndrome secondary to cardiovascular procedures are presented. In Case 1, the patient died 35 days after coronary angioplasty, whereas in Case 2, the patient developed toe necrosis 95 days after endovascular aortic repair, leading to progressive renal failure over the following five years. A comprehensive forensic autopsy included external examination, skin biopsy, histopathological examination of major organs, and serum biochemical evaluation of renal function parameters. Two cases of blue toe syndrome secondary to cardiovascular procedures are presented. In Case 1, the patient died 35 days after coronary angioplasty, whereas in Case 2, the patient developed toe necrosis 95 days after endovascular aortic repair, leading to progressive renal failure over the following five years. A comprehensive forensic autopsy included external examination, skin biopsy, histopathological examination of major organs, and serum biochemical evaluation of renal function parameters. This report underscores the importance of including systemic cholesterol crystal embolism in the differential diagnosis of blue toe syndrome, particularly in patients with a history of cardiovascular procedures. Fingertips serve as reliable indicators of impaired blood perfusion. To assess blue toe syndrome accurately, we highlight the value of focusing on the toe tips where cholesterol crystal embolism can be consistently detected.

Acute hyperglycemia exacerbates neuroinflammation and cognitive impairment in sepsis-associated encephalopathy by mediating the ChREBP/HIF-1α pathway.

Delirium is a prominent symptom of sepsis-associated encephalopathy (SAE) and is highly prevalent in septic patients hospitalized in the intensive care unit, being closely connected with raised mortality rates. Acute hyperglycemia (AH) has been recognized as a separate risk factor for delirium and a worse prognosis in critically sick patients. Nevertheless, the exact contribution of AH to the advancement of SAE is still unknown. This research retrospectively evaluated the connection between blood glucose levels (BGLs) and the incidence of delirium and death rates in septic patients in the ICU of a tertiary comprehensive hospital. In addition, a septic rat model was induced through cecal ligation and puncture (CLP), after which continuous glucose infusion was promptly initiated via a central venous catheter post-surgery to evaluate the potential implications of AH on SAE. Next, septic rats were assigned to four groups based on target BGLs: high glucose group (HG, ≥ 300mg/dL), moderate glucose group (MG, 200-300mg/dL), normal glucose group (NG, < 200mg/dL), and a high glucose insulin-treated group (HI, 200-300mg/dL) receiving recombinant human insulin treatment (0.1IU/kg/min). The sham group (SG) received an equivalent volume of saline infusion and denoted the NG group. The effects of AH on neuroinflammation and cognitive function in septic rats were evaluated using behavioral tests, histopathological examination, TUNEL staining, ELISA, and Western blot. The effects of glucose levels on microglial activation and glucose metabolism following lipopolysaccharide (LPS, 1μg/mL) exposure were assessed using CCK8 assay, qRT-PCR, Western blot, and ELISA. Our findings revealed that AH during sepsis was a separate risk factor for delirium and assisted in predicting delirium occurrence. AH raised the levels of systemic and central inflammatory cytokines in septic rats, promoting neuronal apoptosis, blood-brain barrier disruption, and cognitive impairment. In addition, both in vivo and in vitro, an elevated glucose challenge increased the ChREBP, HIF-1α, glycolytic enzymes, and inflammatory cytokines expressions in microglia after exposure to CLP or LPS. These results collectively suggest that hyperglycemia can exacerbate neuroinflammation and delirium by enhancing microglial glycolysis under septic conditions, potentially mediated by upregulation of the ChREBP/HIF-1α signaling pathway.

Systematic Review of Deep Learning Techniques in Skin Cancer Detection

Skin cancer is a serious health condition, as it can locally evolve into disfiguring states or metastasize to different tissues. Early detection of this disease is critical because it increases the effectiveness of treatment, which contributes to improved patient prognosis and reduced healthcare costs. Visual assessment and histopathological examination are the gold standards for diagnosing these types of lesions. Nevertheless, these processes are strongly dependent on dermatologists’ experience, with excision advised only when cancer is suspected by a physician. Multiple approaches have surfed over the last few years, particularly those based on deep learning (DL) strategies, with the goal of assisting medical professionals in the diagnosis process and ultimately diminishing diagnostic uncertainty. This systematic review focused on the analysis of relevant studies based on DL applications for skin cancer diagnosis. The qualitative assessment included 164 records relevant to the topic. The AlexNet, ResNet-50, VGG-16, and GoogLeNet architectures are considered the top choices for obtaining the best classification results, and multiclassification approaches are the current trend. Public databases are considered key elements in this area and should be maintained and improved to facilitate scientific research.

A SPINAL TRAUMA, A TUMOR AND EVERYTHING IN BETWEEN

Introduction Burkitt lymphoma is a male predominant (3:1 male:female ratio) aggressive B-cell non-Hodgkin lymphoma that can present as a sporadic variant with meningeal involvement in about 20% of cases. Therefore, it can manifest with neurologic deficits due to compression of the spinal cord or spine nerve root. Case Report We report the case of a 6 years-old girl who presented in the emergency department following a traumatic vertebral injury (fall from around 1.5 meters) with no spinal cord involvement. She accused upper back pain, walking and orthostatism difficulties and manifested a light to moderate inferior paraparesis (MCR 3/5) The MRI revealed a space-occupying epidural mass between T1-T4, severely compressing the spinal cord initially thought to be an epidural hematoma. Emergency surgery was performed with duro-radicular decompression and mass excision through a T1-T4 laminotomy followed by a laminoplasty. The unveiled mass was white, minimally vascularized and adherent to the dura raising the suspicion of a tumor. Postoperatively the patient exhibited significant neurological improvement with resolution of the paraparesis and normal gait restoration. Three weeks later, the patient returned with complaints of abnormal gait, lumbar pain radiating in the right lower leg and upon examination a light right lower limb monoparesis (MRC 4/5) following another traumatic event. Emergency MRI of the whole spine with contrast was requested just as the pathologist in charge of the case suggested a diagnosis of Burkitt lymphoma, prompting a whole-body MRI. A severe recurrence was noted at the site of the previous lesion along with a new lumbar lesion, and several intraabdominal, intrathoracic, ovarian tumor sites with diffuse infiltration of the bone marrow. The patient was urgently referred to the pediatric oncology department and started on steroidal anti-inflammatory treatment and chemotherapy. Conclusions Burkitt lymphoma involving the nervous system in children requires increased medical attention during the clinical, histopathological examination and treatment phase, due to the association with advanced disease and, although rare, should be considered as a differential diagnosis in pediatric patients with epidural lesions. The management of such lesions demands a solid collaboration between neurosurgeon, pediatrician, pathologist and oncologist for an early diagnosis and proper treatment.

Retinoic acid ameliorates rheumatoid arthritis by attenuating inflammation and modulating macrophage polarization through MKP-1/MAPK signaling pathway.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.