Defining the Etiology of Renal Allograft Dysfunction Using Banff 2019 Classification: Correlation with Post-Transplant Duration and Creatinine Levels-A Comprehensive Analysis of 200 Renal Biopsies at a Tertiary Care Medical Center Hospital.

OBJECTIVE: Chronic kidney disease is a growing global health issue, contributing significantly to morbidity and mortality. The incidence of end-stage renal disease (ESRD) is approximately 100 per million population. Renal transplantation remains the cornerstone treatment for ESRD, with a projected 20-year survival rate of 60%. We aim to define the etiology of renal allograft dysfunction using the Banff 2019 classification by analyzing 200 renal allograft biopsies in correlation with creatinine levels across post-transplant time frames. METHODOLOGY: 200 renal allograft biopsies are analyzed using the recent Banff 2019 classification with creatinine levels and post-transplant duration correlation. RESULTS: The study included 150 (75%) male patients and 50 (25%) female patients, with the majority 78 (39%) representing the age group of 16-30 years. 36 (18%) biopsies were within 3-month post-transplant, while 92 (46%) were 2-year post-transplant. According to the Banff 2019 classification, 92 (46.0%) transplant rejection biopsies were identified, with most 54 (27%) exhibiting antibody-mediated rejection (Category 2), including 40 (20%) active acute antibody-mediated rejection (ABMR) and 14 (7.0%) chronic active ABMR. T-cell-mediated rejection (TCMR; Category 4) represented 12 (6%) biopsies, including 10 (5%) acute TCMR and 2 (1%) chronic active TCMR. Category 5, the miscellaneous group, represented 100 (50%) biopsies, out of which 32 (16%) exhibited calcineurin inhibitor (CNI) toxicity, 38 (19%) acute tubular necrosis, and 8 (4%) thrombotic microangiopathy. A notable variation in the dysfunction distribution across different post-transplant time frames indicated a temporal evolution in the underlying causes of allograft dysfunction. Specific Banff categories showed a robust association with renal dysfunction, potentially contributing to the elevation of creatinine levels and renal function deterioration. CONCLUSION: Our study highlights the intricate pathophysiology of renal allograft dysfunction. Most biopsies were attributed to ABMR whereas one-third of biopsies exhibited mixed lesions (ABMR and TCMR or ABMR and calcineurin inhibitor toxicity (CNIT)). Additionally, this study suggests that renal allograft rejection remains a significant contributor to graft dysfunction. A complex interplay between histological findings, Banff classification, and renal function is noted. A significant difference in the distribution of dysfunction across post-transplant time frames is noted suggesting a temporal evolution in the etiology of allograft dysfunction. Certain Banff categories demonstrate a stronger association with renal dysfunction that may influence creatinine level increase and renal function deterioration. In correspondence to the recent Banff 2019 guidelines for diagnosing ABMR, we emphasize the role of C4d staining on immunofluorescence or immunohistochemistry in allograft biopsies as imperative for timely diagnosis and immunosuppressant therapy adjustment, ultimately enhancing graft survival. Further research is needed to elucidate the underlying mechanisms driving renal dysfunction in different Banff categories, ultimately informing personalized management strategies for patients with renal allograft dysfunction. In line with the Banff 2019 guidelines for diagnosing ABMR, this study highlights the critical role of C4d staining through immunofluorescence or immunohistochemistry in allograft biopsies for early diagnosis and timely adjustment of immunosuppressive therapy, ultimately improving graft survival.

Unveiling the Rarity: CD20 Expression in Mycosis Fungoides and Its Clinical Significance.

ABSTRACT: Although CD20 expression is typically scarce in mycosis fungoides (MF), it is more commonly associated with T-cell lymphomas. Nevertheless, isolated instances of CD20-positive MF have been documented infrequently. Here, we present a unique case of CD20-positive MF in a 30-year-old man who manifested with a hypopigmented patch on the anterior chest. Histopathological examination revealed epidermotropic infiltrates of small- to medium-sized lymphocytes with hyperchromatic and cerebriform nuclei aligned along the basal and low-mid layers of the epidermis. Immunophenotypic analysis demonstrated neoplastic T cells expressing CD4+, CD8+, and CD3+ with the loss of CD7. Intriguingly, a notable subset of the neoplastic T cells exhibited CD20 expression. This case contributes to the sparse literature on CD20-positive MF and underscores its diagnostic and clinical ramifications. The role of B cells has been more thoroughly characterized in T-cell lymphomas other than MF. However, its significance in MF remains unclear due to the scarcity of reported cases. Some hypotheses propose that the B cells' expression might indicate immune dysregulation or complex interactions within the tumor microenvironment. Another perspective suggests it could signify a progression of the disease towards a more aggressive lymphoma phenotype. Further investigation and documentation of similar cases is imperative to elucidate the clinical features, prognosis, and optimal therapeutic strategies. The long-term prognosis and outcomes in patients with hypopigmented MF and CD20 positivity remain ambiguous, underscoring the necessity for continued research and scrutiny of analogous cases.

Navigating Diagnostic and Therapeutic Challenges in Primary Cutaneous Gamma/Delta T-Cell Lymphoma: A Case Study of Fatal Outcomes Within Two Months.

ABSTRACT: Primary cutaneous gamma/delta T-cell lymphoma (PCGD-TCL) is a rare yet highly aggressive subtype of primary cutaneous lymphoma. Characterized by its challenging diagnosis and poor prognosis, PCGD-TCL presents unique clinical and histopathological features that distinguish it from other primary cutaneous lymphoma subtypes. Here, we report the case of a 75-year-old man who initially presented with multiple erythematous indurated plaques over his back and bilateral lower extremities. The initial biopsy suggested primary cutaneous T-cell lymphoma (PCTCL) with a CD30-negative phenotype. However, within a 2-month interval, the disease progressed rapidly, manifesting as extensive skin involvement across the chest and upper extremities. A repeat skin biopsy was performed, revealing dermal atypical lymphocytes without epidermotropism. Immunohistochemical analysis demonstrated positivity for CD3, CD5, and CD4, as well as T-cell receptor delta (TCR delta) expression, along with the loss of CD8 and CD30 expression. These findings were consistent with a diagnosis of PCGD-TCL. Despite therapeutic interventions, including systemic treatments, the patient's condition deteriorated rapidly, ultimately leading to his demise within a month of receiving the PCGD-TCL diagnosis. This case highlights the diagnostic complexities associated with PCGD-TCL, emphasizing the importance of careful histopathological examination and immunophenotypic characterization. Given its aggressive nature and propensity for rapid dissemination, early recognition of PCGD-TCL is paramount for initiating appropriate therapeutic interventions. However, effective treatment options for PCGD-TCL remain limited, and the disease typically carries an unfavorable prognosis. Further research is needed to elucidate the underlying molecular mechanisms driving the pathogenesis of PCGD-TCL, to identify novel therapeutic targets, and to improve patient outcomes. In addition, increased awareness among clinicians and pathologists regarding the clinical presentation and diagnostic criteria of PCGD-TCL is crucial for facilitating timely diagnosis and management of this challenging malignancy.

Autogenic training for chronic health conditions: A service evaluation.

BACKGROUND: Autogenic training (AT) is a structured meditative-style practice, consisting of a sequence of simple mental exercises intended to induce a relaxed state in patients. There is some emerging evidence to suggest that AT can be effective in treating certain chronic conditions, however, further evidence is required. A service evaluation of AT services at the Royal London Hospital for Integrated Medicine was conducted to evaluate the impact of AT on patients with chronic conditions. METHODS: The service evaluation consisted of the completion of validated quantitative outcome measures pre and posttreatment to explore the impact of AT. AT patients were asked to complete the Measure Yourself Medical Outcomes Profile (MYMOP) and Perceived Stress Scale (PSS) at their first hospital appointment (baseline) and then again 8 weeks later following completion of their AT sessions. Pre- and posttreatment scores for each outcome measure were analysed in SPSS using the Wilcoxon signed-rank test. RESULTS: One hundred ninety-nine patients completed both initial and follow-up MYMOP forms and were included in the evaluation. The most common presenting complaints for MYMOP symptom 1 were prolonged anxiety/stress and depression (n = 70, 35.2%), chronic pain and migraine headache (n = 44, 22.1%), chronic insomnia and sleep problems (n = 42, 21.1%) and, long-term exhaustion and fatigue (n = 18, 9%). The change in median score pre- and posttreatment for all MYMOP categories (symptoms, activity and well-being) were statistically highly significant p < 0.001. Anxiety, stress, depression, pain and insomnia were the symptoms that had the largest statistically significant difference between the median score pre- and posttreatment. Fifty-five patients completed the PSS questionnaire at two time points (pre- and posttreatment). It showed a highly statistically significant change in PSS median score in patients experiencing stress (p < 0.001). DISCUSSION: The findings of the evaluation indicate that 8 weeks of AT appears to be effective in improving symptoms of concern to patients and enhancing patients' overall well-being. In particular, AT was found to be beneficial for patients with symptoms of anxiety, stress, depression, pain and insomnia.

Delayed Diagnosis of SMARCA4-Deficient Undifferentiated Tumor in a Heavy Smoker Male Patient: Discovered Through Bone Sampling, with Extensive Distant Metastases and Concurrent Granulomatous Disease, Leading to Patient Fatality.

Background. SMARCA4-deficient undifferentiated tumors are rare and pose a diagnostic challenge. This study delves into the intricate diagnostic terrain of SMARCA4-deficient undifferentiated tumors, providing insights into their diverse clinical presentations and diagnostic approaches. Case Presentation. A 69-year-old heavy-smoker man with adalimumab-treated rheumatoid arthritis presented with multiple lesions. A CT scan revealed a spiculated lung mass, enlarged mediastinal lymph nodes, and hepatic lesions. A whole-body FDG-PET/CT scan revealed heterogeneous hypermetabolic lesions in the lung, liver, and bone. Initial two core needle liver biopsies and a left upper lobe lung wedge resection initially indicated steatohepatitis and granulomatous formation with no evidence of malignancy. Several months later, the patient returned with left-sided flank pain and significant weight loss. CT scan identified a thigh mass, adrenal lesion, and extensive multiple skeletal lesions. A biopsy of the thigh mass revealed an extensively necrotic, epithelioid-to-spindled cell neoplasm with positive staining for pan keratin, focal staining for CD56, and a loss of nuclear expression of SMARCA4. A final diagnosis of SMARCA4-deficient undifferentiated tumor was rendered. Unfortunately, the patient's condition deteriorated, and he died a few weeks after receiving the final diagnosis. Conclusion. SMARCA4-deficient undifferentiated tumors have emerged as recent subjects of medical study, distinguished by their unique morphology and SMARCA4-deficient immunohistochemistry. These tumors present diverse clinical manifestations, affecting multiple organ systems. This report underscores the diagnostic complexities associated with complex clinical presentation and highlights the importance of multidisciplinary collaboration in addressing challenging clinical scenarios, particularly among heavy smoker male patients and intricate radiological presentations.

Fumarate Hydratase-Deficient Abdominal Wall Leiomyoma Presenting a Decade Post-Fumarate Hydratase-Deficient Uterine Leiomyoma Excision: An Incidental or Syndromic Association?

Background. The occurrence of fumarate hydratase-deficient leiomyoma of the abdominal wall is exceptionally rare. Case Presentation. A 50-year-old female patient with a past medical history of fumarate hydratase-deficient uterine leiomyoma presented with a left lower quadrant abdominal mass that has been present for the past 2 years. An ultrasound revealed a 3.5 cm oval hypoechoic mass. A subsequent CT scan showed a 3.5 cm hyperdense mass within the left internal oblique musculature. No family history is noted. A biopsy of the mass exhibited bundles of spindle cell neoplasm exhibiting bizarre ovoid nuclei and eosinophilic cytoplasm. No evidence of mitotic figures or tumor necrosis was noted. Immunohistochemical staining showed positive staining for desmin and smooth muscle actin (SMA), but negative staining for MART-1, S100, and CD34. Lesional cells showed expression of 2-succinocysteine and loss of fumarate hydratase expression. A diagnosis of fumarate hydratase-deficient leiomyoma was rendered. Conclusion. This report reinforces the importance of considering genetic testing for fumarate hydratase mutations in the evaluation of extra-uterine leiomyomatous lesions. Comprehensive follow-up and clinical screening in individuals with new lesions and a known history of fumarate hydratase-deficient neoplasms is mandatory. Recent recommendations support the integration of morphology-based evaluation along with immunohistochemical staining and genetic testing as a part of the standard evaluation for all uterine leiomyomas.

Unveiling the Uncommon: Gastrointestinal Basidiobolomycosis of the Colon and its Distinctive Splendore-Hoeppli Phenomenon.

BACKGROUND: Basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum. CASE PRESENTATION: A 53-year-old man from Saudi Arabia with a known history of diverticulosis presented with severe abdominal pain and diarrhea. A CT scan revealed circumferential wall thickening of the descending and sigmoid colon with surrounding fat stranding, suggesting a diagnosis of complicated diverticulitis. Additional thick fluid was observed around the affected area. Surgical excision was pursued. A gross examination of two received large bowel segments disclosed marked ulcerated mucosa and wall thickening with exudate-covered serosal surfaces and adhesions. Microscopic examination unveiled significant infiltration by eosinophils, polymorphonuclear leukocytes, and granulomatous inflammation. Thin-walled, broad fungal hyphae of Basidiobolus, surrounded by eosinophilic material, were identified. Granulomas displayed abundant multinucleated giant cells and palisading histiocytes around central necrosis or abscess formation. Thin-walled, broad fungal hyphae of Basidiobolus, with sparse septations, are surrounded by a radiating, intensely eosinophilic cuff (Splendore-Hoeppli phenomenon). These hyphae, visible with hematoxylin and eosin staining, were further highlighted with periodic acid-Schiff and Gomori methenamine silver staining. DISCUSSION: Basidiobolomycosis may mimic neoplastic lesions. Histologically, the characteristic features include broad, thin-walled septate hyphae surrounded by eosinophilic material, a finding that is accentuated by the Splendore-Hoeppli phenomenon. Microscopic examination, along with special stains such as periodic acid-Schiff (PAS) and Gomori methenamine silver, is essential for accurate diagnosis. CONCLUSION: Prompt recognition and appropriate antifungal therapy are vital for favorable patient outcomes. This report highlights the distinctive features of Basidiobolomycosis to raise awareness and understanding of this infrequent yet clinically significant fungal infection.

Cytopathology in the era of social media.

In today's medical landscape, social media (SoMe) platforms have expanded their reach beyond mere communication and entertainment, making a significant impact in the pathology field, including cytopathology. In recent years, SoMe platforms have become increasingly adopted by cytopathologists, facilitating continued education, professional networking, enhancing patient engagement, and entertainment. This adoption has influenced the professional growth of cytopathologists, and at its best, has led to the establishment of a robust professional online presence and ultimately contributed to leadership positions, fellowship opportunities, and academic promotions. Moreover, the integration of SoMe into the academic field has shown a profound impact on the visibility of academic journals and has provided a platform for lower-impact factor journals to expand their reach, ultimately increasing article citation rates and positively contributing to journal impact factor growth. SoMe platforms created a modern avenue for conference networking that has revolutionized knowledge dissemination and enhanced real-time engagement. The advantages of SoMe have extended to a global scale, positively enhancing professional expertise sharing, facilitating effective communication and teleconsultation worldwide, and reaching developing countries. Drawing insights from the recent medical literature and the practical insight from the experts' personal experience, this article provides a comprehensive review of how SoMe and cytopathology intersect to create new opportunities, facilitating informed discussions, global collaboration, and advancements in the field of cytopathology. This article also delves into the challenges surrounding SoMe platform navigation and addresses ethical and regulatory concerns, providing guidelines on what to post and what not to post on SoMe platforms.

Vinpocetine alleviated alveolar epithelial cells injury in experimental pulmonary fibrosis by targeting PPAR-γ/NLRP3/NF-κB and TGF-ß1/Smad2/3 pathways.

This study aimed to investigate the potential anti-fibrotic activity of vinpocetine in an experimental model of pulmonary fibrosis by bleomycin and in the MRC-5 cell line. Pulmonary fibrosis was induced in BALB/c mice by oropharyngeal aspiration of a single dose of bleomycin (5 mg/kg). The remaining induced animals received a daily dose of pirfenidone (as a standard anti-fibrotic drug) (300 mg/kg/PO) and vinpocetine (20 mg/kg/PO) on day 7 of the induction till the end of the experiment (day 21). The results of the experiment revealed that vinpocetine managed to alleviate the fibrotic endpoints by statistically improving (P ≤ 0.05) the weight index, histopathological score, reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. It also alleviated tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators significantly elevated in bleomycin-only induced animals (P ≤ 0.05). Vinpocetine managed to express a remarkable attenuating effect in pulmonary fibrosis both in vivo and in vitro either directly by interfering with the classical TGF-ß1/Smad2/3 signaling pathway or indirectly by upregulating the expression of Nrf2 enhancing the antioxidant system, activating PPAR-γ and downregulating the NLRP3/NF-κB pathway making it a candidate for further clinical investigation in cases of pulmonary fibrosis.

Anti-cytokine Storm Activity of Fraxin, Quercetin, and their Combination on Lipopolysaccharide-Induced Cytokine Storm in Mice: Implications in COVID-19.

Background: Cytokine release syndrome (CRS) is the leading cause of mortality in advanced stages of coronavirus patients. This study examined the prophylactic effects of fraxin, quercetin, and a combination of fraxin+quercetin (FQ) on lipopolysaccharide-induced mice. Methods: Sixty mice were divided into six groups (n=10) as follows: control, LPS only, fraxin (120 mg/Kg), quercetin (100 mg/Kg), dexamethasone (5 mg/Kg), and FQ. All treatments were administered intraperitoneally (IP) one hour before induction by LPS (5 mg/Kg) IP injection. Twenty-four hours later, the mice were euthanized. Interleukin one beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were quantified using an enzyme-linked immunosorbent assay (ELISA), and lung and kidney tissues were examined for histopathological alterations. This study was conducted at Al-Nahrain University, Baghdad, Iraq, in 2022. Results: FQ reduced IL-1ß (P<0.001). All treatments significantly suppressed IL-6, fraxin, quercetin, dexamethasone, and FQ, all with P<0.001. The TNF-α level was reduced more with dexamethasone (P<0.001) and quercetin (P<0.001). Histopathological scores were significantly reduced mainly by quercetin and FQ in the lungs with scores of 12.30±0.20 (P=0.093), and 15.70±0.20 (P=0.531), respectively. The scores were 13±0.26 (P=0.074) and 15±0.26 (P=0.222) for quercetin and FQ in the kidneys, respectively. Conclusion: All used treatments reduced proinflammatory cytokine levels and protected against LPS-induced tissue damage.