Epstein-Barr virus latency patterns in polymorphic lymphoproliferative disorders and lymphomas in immunodeficiency settings: Diagnostic implications.

Epstein-Barr virus (EBV) is responsible for many B cell lymphoproliferative disorders (LPD) spanning subclinical infection to immunodeficiency-related neoplasms. EBV establishes a latent infection in the host B cell as defined histologically by the expression of EBV latent membrane proteins and nuclear antigens. Herein, we characterize the latency patterns of immunodeficiency-related neoplasms including post-transplant lymphoproliferative disorders (PTLD) and therapy-related LPD (formerly iatrogenic) with latent membrane protein-1 (LMP-1) and EBV nuclear antigen-2 (EBNA-2) immunohistochemistry. The latency pattern was correlated with immunodeficiency and dysregulation (IDD) status and time from transplant procedure. 38 cases of EBV+ PTLD in comparison to 27 cases of classic Hodgkin lymphoma (CHL) and diffuse large B cell lymphoma (DLBCL) arising in either the therapy-related immunodeficiency setting (n = 12) or without an identified immunodeficiency (n = 15) were evaluated for EBV-encoded small RNAs by in situ hybridization (EBER-ISH) and for LMP-1 and EBNA-2 by immunohistochemistry. A full spectrum of EBV latency patterns was observed across PTLD in contrast to CHL and DLBCL arising in the therapy-related immunodeficiency setting. Polymorphic-PTLD (12 of 16 cases, 75 %) and DLBCL-PTLD (9 of 11 cases, 82 %) showed the greatest proportion of cases with latency III pattern. Whereas, EBV+ CHL in an immunocompetent patient showed exclusively latency II pattern (13 of 13 cases, 100 %). The majority of EBV+ PTLD occurred by three years of transplant procedure date and were enriched for latency III pattern (21 of 22 cases, 95 %). Immunohistochemical identification of EBV latency by LMP-1 and EBNA-2 can help classify PTLD in comparison to other EBV+ B cell LPD and lymphomas arising in therapy-related immunodeficiency and non-immunodeficiency settings.

Targeted mutational profiling of Epstein Barr virus-positive mucocutaneous ulcer: Implications for differential diagnosis with EBV-positive diffuse large B-cell lymphoma.

Epstein Barr Virus-positive mucocutaneous ulcer (EBVMCU) can be difficult to distinguish from EBV-positive diffuse large B cell lymphoma (DLBCL). We used targeted next-generation sequencing (NGS) to explore genetic alterations in EBVMCU to aid in this diagnostic challenge. Ten cases of EBVMCU were evaluated by a targeted NGS panel of 164 genes. Targeted NGS identified 18 variants in 15 genes in eight cases of EBVMCU. Loss of function TET2 variants were most frequently identified (3 of 10 cases, 30 %). One TET2 variant occurred at low variant allele frequency (VAF) of 3 %, which may be suggestive of clonal hematopoiesis of indeterminate potential. One case harbored a loss of function DNMT3A variant at low VAF. Two cases demonstrated missense variants in the IRF8 gene. Both variants occurred at a VAF close to 50 % and with an estimated high burden of disease (75 %). Two cases of mucosal gastrointestinal involvement had no reportable variants. Mutational profiling of EBVMCU identified TET2 loss of function variants at an elevated frequency in our cohort; however, the findings are not specific and its clinical significance cannot be completely elucidated. Further studies are needed to confirm the findings in an independent and larger cohort of EBVMCU, to determine the cell of origin of the variants, and to further assess their significance in the pathogenesis of this disorder.

Versatile Magnetic Mesoporous Carbon Derived Nano-Adsorbent for Synchronized Toxic Metal Removal and Bacterial Disinfection from Water Matrices.

Contamination of water resources by toxic metals and opportunistic pathogens remains a serious challenge. The development of nano-adsorbents with desired features to tackle this problem is a continuously evolving field. Here, magnetic mesoporous carbon nanospheres grafted by antimicrobial polyhexamethylene biguanidine (PHMB) are reported. Detailed mechanistic investigations reveal that the electrostatic stabilizer modified magnetic nanocore interfaced mesoporous shell can be programmatically regulated to tune the size and related morphological properties. The core-shell nano-adsorbent shows tailorable shell thickness (≈20-55 nm), high surface area (363.47 m2 g-1 ), pore volume (0.426 cm3 g-1 ), radially gradient pores (11.26 nm), and abundant biguanidine functionality. Importantly, the nano-adsorbent has high adsorption capacity for toxic thallium (Tl(I) ions (≈559 mg g-1 ), excellent disinfection against Staphylococcus aureus and Escherichia coli (>99.99% at 2 and 2.5 µg mL-1 ), ultrafast disinfection kinetics rate (>99.99% within ≈4 min), and remarkable regeneration capability when exposed to polluted water matrices. The Tl(I) removal is attributed to surface complexation and physical adsorption owing to open ended mesopores, while disinfection relies on contact of terminal biguanidines with phospholipid head groups of membrane. The significance of this work lies in bringing up effective synchronic water purification technology to combat pathogenic microorganisms and toxic metal.

Bullous impetigo on a young man's abdomen.

Bullous impetigo is a variant of epidermal infection by Staphylococcus aureus, representing 30% of impetigo cases. Its clinical appearance may mimic certain autoimmune blistering dermatoses and other cutaneous infections, sometimes necessitating careful evaluation. Herein we present a patient with bullous impetigo in a striking and characteristic appearance and briefly overview the approach to diagnosis, treatment, and prevention.

Cutaneous larva migrans in the northeastern US.

Cutaneous larva migrans (CLM) is a dermo-epidermal parasitic infection with a disproportionate incidence in developing countries, particularly in, and near tropical areas. It is characterized by erythematous, twisting, and linear plaques that can migrate to adjacent skin. Herein, we present an otherwise healthy 45-year-old woman who acquired a pruritic, erythematous, and serpiginous rash localized to her right medial ankle during a trip to New England. Oral ivermectin, the preferred first-line treatment for cutaneous larva migrans, was administered in combination with triamcinolone. This was followed by removal of the papular area via punch biopsy; treatment was successful with a one-week recovery. Although cutaneous larva migrans has traditionally been considered a tropical disease, clinicians should be cognizant of its expanding geographic spread.

Immunohistochemistry in melanocytic lesions: Updates with a practical review for pathologists.

This review provides a summary of the immunohistochemical markers pertinent to the diagnosis of melanocytic lesions. There is considerable morphologic overlap between benign and malignant melanocytic lesions, and given the significant differences in clinical management, the diagnostic workup becomes crucial. Immunohistochemistry aids in the distinction between various melanocytic proliferations and recent contributions to the literature have furthered our optimization of panels in the diagnostic workup. In recent years, SOX10 has been considered as the optimal marker for melanocytic lesions given the similar sensitivity but higher specificity than S100. HMB-45 is less sensitive than S100 but demonstrates utility in confirmation of deceptively banal small cell and nevoid melanoma variants where deep nests of melanocytes are highlighted. Melan-A (MART-1) and MiTF show similar sensitivity to S100 however there is a lack of expression in spindle cell and desmoplastic melanomas.

Cd diminution through microbial mediated degraded lignocellulose maize straw: Batch adsorption and bioavailability trails.

Lignocellulose degraded maize straw (LMS) was prepared with the interaction of soil-indigenous microorganisms and further deployed to attenuate the Cd contamination in polluted soil. The Lignocellulose degrading ratio was determined and results revealed the significant degradation of cellulose, hemicellulose and lignin by 33.03, 26.7 and 15.97% respectively as compared to pristine maize straw (PS). Moreover, LMS was also categorized through FE-SEM, FTIR, BET analysis, elemental analysis and XPS technique and the analytical results indicated that lignocellulose structure in maize straw was successfully degraded and was involved in metal-ion complexation. Batch sorption trials revealed that Cd2+ sorption onto LMS was explained well by Langmuir isotherm and pseudo-second-order kinetic model. The LMS showed maximum adsorption capacities (9.84 mg g-1) for Cd2+ as compared to PS (3.30 mg g-1). Moreover, the soil incubation trials (60 days) depicted the availability of Cd decreased by 11.03 and 34.7% with PS and LMS application respectively. The addition of LMS significantly decreased the exchangeable fractions of Cd and ensued an increase in organic matter and Fe-Mn oxides bound fractions. This work clarified the LMS as a promising amendment for effective remediation of Cd-contaminated matrices.

Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoproliferative disorder in a young woman.

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+PCSM-LPD) is a low-grade cutaneous T cell disorder. There is no standardized approach to treatment of CD4+ PCSM-LPD due to its rarity. Herein, we discuss a 33-year-old woman with CD4+PCSM-LPD which resolved after a partial biopsy. We highlight that conservative and local treatment modalities should be considered prior to utilizing more aggressive and invasive treatment options.

Cutaneous cytomegalovirus - A case of disseminated cytomegalovirus presenting with extensive ulcerative skin lesions in a renal transplant recipient.

Cytomegalovirus (CMV) reactivation is common in organ transplant recipients and can lead to significant morbidity and mortality. Cutaneous CMV findings are rarely reported in the literature and diagnosis can be delayed if not clinically recognized. We describe a case of a female patient 20 years post renal transplant who presented with extensive ulcerative skin lesions and diarrhea. She rapidly deteriorated and died on day 5 of hospitalization. Autopsy noted extensive CMV involvement of skin and gastrointestinal (GI) tract by CMV-specific immunohistochemistry. These findings, along with high-grade CMV viremia, led to the final postmortem diagnosis of disseminated CMV infection. This case focuses on the cutaneous findings of disseminated CMV as recognition of CMV skin lesions can lead to earlier initiation of appropriate therapy in transplant recipients.

Enhanced removal of Cr(III)-EDTA chelates from high-salinity water by ternary complex formation on DETA functionalized magnetic carbon-based adsorbents.

A novel amino-functionalized magnetic adsorbent (Fe3O4@C@DETA) was developed for adsorption of Cr(III) and Cr(III)-EDTA from wastewater. Fe3O4@C@DETA were successfully prepared by modification of Fe3O4@C with diethylenediamine (DETA), which exhibits a core-shell structure and sufficient saturation magnetization. Fe3O4@C@DETA exhibits much better adsorption performance for Cr(III) and its chelates than the Fe3O4@C because of newly introduced amino active sites. The enhanced adsorption capacity of Fe3O4@C@DETA for Cr(III) is 44.74 mg g-1 (at 25 °C and pH 3.0), which is due to the surface coordination with the newly introduced amino functional sites. The Cr(III)-EDTA anions as a whole was adsorbed through the electrostatic interaction with protonated amino species of the Fe3O4@C@DETA and have maximum adsorption capacity of 47.27 mg g-1 (at 25 °C and pH 3.0). The adsorption data of free and EDTA coordinated Cr(III) were followed the Langmuir equation, while the adsorption dynamics was well explained by pseudo second order model indicating the chemical nature of adsorption process. The higher concentration of Ca2+ ions in the wastewater compete for adsorption sites and inhibit the Cr(III) removal, while on other hand Ca2+ ions promotes the adsorption of Cr(III)-EDTA, because of electrostatic interaction with adsorbent active sits. Furthermore, the adsorbent can be easily separated by external magnetic field and regenerated in acidic solution. The adsorbent is stable, recyclable and have more than 75% regeneration efficiency and can be repeatedly used in the adsorption process.

Fungal prostatitis due to endemic mycoses and Cryptococcus: A multicenter case series.

BACKGROUND: Fungal prostatitis is exceedingly rare with mostly case reports. METHODS: Electronic medical records at three medical centers were searched for cases of fungal prostatitis due to endemic mycoses and Cryptococcus over the preceding 10 years. RESULTS: Seven cases were identified from 105 600 prostate biopsies within the Southern California Permanente Medical Group for an incidence of 0.0066%. An additional eight cases were identified from two other health care systems. Excluding four patients without available clinical data, 11 patients were reviewed, most of whom underwent biopsy due to elevated prostate-specific antigen. Four were asymptomatic and the remainder had nonspecific signs or symptoms. All biopsies revealed granulomatous inflammation and fungal organisms. Seven patients had coccidioidomycosis, three patients had cryptococcosis (confirmed in two cases and suspected by organism morphology in the other), and one patient had likely histoplasmosis based on organism morphology. Prolonged antifungal treatment was standard; outcomes were favorable. CONCLUSION: Fungal prostatitis due to endemic mycoses and Cryptococcus is uncommon and associated with favorable outcomes but generally involves prolonged therapy.

Intralymphatic Rosai-Dorfman Disease Associated With Vulvar Lymphedema: A Case Report of an Extremely Rare Phenomenon.

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD), is a self-limited histiocytic disorder of unclear etiology which most commonly presents with cervical lymphadenopathy. Purely extranodal presentation of RDD is uncommon, and isolated intralymphatic/intravascular confinement of this entity has not previously been described. We report a 16-yr-old female who presented with vaginal swelling and mass-like enlargement of the right labia. The mass had been present for nearly a year without pain or tenderness. Clinically, the lesion was thought to be a Bartholin gland cyst. Following surgical resection, histologic examination demonstrated a hypocellular myxedematous stroma with a mixture of ectatic thin and thick-walled vessels within which there were numerous collections of histiocytes, lymphocytes, and plasma cells. The histopathologic differential diagnosis included localized vulvar lymphedema, a specialized genital tract neoplasm, and childhood asymmetric labium majus enlargement. The histiocytes showed occasional plasma cells and lymphocytes within their cytoplasm, consistent with emperipolesis. Immunohistochemical studies showed that the histiocytes expressed CD163 and S100, while ERG and D2-40 highlighted their intralymphatic confinement, ultimately leading to the diagnosis of intralymphatic RDD. Intralymphatic RDD may present as vulvar lymphedema and can potentially mimic other myxedematous neoplasms of the vulvovaginal region.

Extranodal NK/T-Cell Lymphomas: The Role of Natural Killer Cells and EBV in Lymphomagenesis.

Keywords: NK cells, extranodal NK/T-cell lymphoma, EBV.

Outcomes and Predictors of Rebleeding After 2-Octyl Cyanoacrylate Injection in Acute Gastric Variceal Hemorrhage.

BACKGROUND AND AIM: Endoscopic injection of 2-octyl cyanoacrylate (2-OCA) is used on an off-label basis for gastric variceal hemorrhage (GVH) in the United States. We assessed the efficacy, safety, and predictors of rebleeding after gastric variceal obturation (GVO) with 2-OCA in patients with acute GVH. MATERIALS AND METHODS: A retrospective analysis was performed of patients with GVH who underwent 2-OCA injection for GVO over a 15-year period. Rates of acute hemostasis, predictors of rebleeding, and cyanoacrylate-related adverse events were assessed. RESULTS: A total of 95 patients (63 males, median age 59±14 y) were analyzed. Gastric varices were categorized as GOV-1 (3%), GOV-2 (61%), and isolated gastric varices type 1 (36%) per Sarin classification. Initial hemostasis was achieved in all patients. Successful GVO, defined as sustained hemostasis within a month after injection, was achieved in 87 (92%) patients. Failed GVO with in-hospital rebleeding was observed in 8 (8%) patients. On univariate analysis, only the model for end-stage liver disease score was associated with an increased risk of rebleeding (odds ratio 1.2; 95% confidence interval, 1.1-1.4; P<0.01). Glue-related adverse events consisted of pulmonary emboli in 2 patients (2.1%), resulting in death in 1 patient. All cause in-hospital mortality was 13% due to uncontrolled gastric variceal rebleeding (n=3), renal failure (n=6), metastatic hepatocellular carcinoma (n=1), hemorrhagic stroke (n=1), and pulmonary embolism (n=1). CONCLUSIONS: Injection of 2-OCA was effective at achieving hemostasis in a high proportion of patients (92%) admitted for acute GVH. The risk of glue-related pulmonary embolism approximated 2% in our patient cohort, including 1 fatality.

Voltage-gated potassium channel antibody-associated limbic encephalitis.

We are emphasising the importance of considering a rare diagnosis, voltage-gated Potassium channel antibody-associated limbic encephalitis, in an 80-year-old gentleman who presented with memory impairment, seizure and hyponatraemia. He was found to have high titre of voltage-gated potassium channel antibodies in his serum. He was given high-dose steroids and he responded biochemically and clinically with marked improvement in symptomatology.

Reduction in Average Length-of-Stay in Emergency Department of a Low-Income Country's Cancer Hospital.

Introduction: Prolonged length of stay (LOS) in emergency departments (ED) is a widespread problem in every hospital around the globe. Multiple factors cause it and can have a negative impact on the quality of care provided to the patients and the patient satisfaction rates. This project aimed to ensure that the average LOS of patients in a tertiary care cancer hospital stays below 3 hours. Materials and Methods: The Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) approach was followed. Results: The average LOS was 166 minutes before implementing interventions. The two primary reasons for the increased length of stay were delays secondary to physician assessment and diagnostic lab reports. Strategies were defined to control these factors, which helped reduce the average length of stay to 142 minutes, a 30% reduction. Conclusion: A process improvement model similar to this project is recommended to enhance the quality of hospital services. It will provide valuable insights into the process flow and assist in gathering precise data on the various steps involved. The data collected can then be analyzed to identify potential causes and make informed decisions that can significantly improve hospital processes.

Histopathologic and Clinical Characterization of Brentuximab Vedotin-associated Rash.

Rash is one of the commonly observed adverse events with brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate used to treat cutaneous T-cell lymphoma (CTCL). However, clinical and histopathologic characterization of BV-associated rash (BVAR) is limited. Distinguishing BVAR from a patient's underlying CTCL can be challenging and can lead to treatment interruptions or even premature drug discontinuation. We performed a thorough clinical and histopathologic retrospective characterization of BVAR from a single institution. Utilizing polymerase chain reaction (PCR) and T-cell receptor high-throughput sequencing (TCR-HTS), we were able to isolate skin biopsy specimens from rash clinically suggestive of BVAR that also lacked a dominant TCR clone. A retrospective evaluation was performed of 26 biopsy specimens from 14 patients. Clinical features of BVAR included predominantly morbilliform or maculopapular morphology, delayed onset, and the trend toward moderate to severe classification, often requiring oral steroids. Most histopathologic specimens (25/26) showed spongiotic dermatitis as the primary reaction pattern. Many cases showed subtle findings to support a background interface or lichenoid eruption. Langerhans cell microabscesses were seen in one-fourth of specimens, and eosinophils were present in over one-half of the specimens. There were focal features mimicking CTCL, but these were not prominent. In 17 specimens with immunohistochemistry, the CD4:CD8 ratio in intraepidermal lymphocytes was relatively normal (1-6:1) in 65% (11/17) and 1:1 in 35% (6/17), demonstrating a trend toward increased CD8-positive cells compared with baseline CTCL. We have identified features that can help distinguish BVAR from a patient's CTCL, which can, in turn, help guide appropriate clinical management.

Insight from the association between critical thinking and English argumentative writing: catering to English learners' writing ability.

Introduction: English argumentative writing (EAW) is a 'problem-solving' cognitive process, and its relationship with critical thinking has drawn attention in China. This is because fostering EAW proficiency is a crucial element but a challenging task for Chinese high school English teaching and learning. The present study examined how critical thinking is related to Chinese high school students' EAW performance. The study identified eight critical thinking disposition (CTD) subscales and aims to determine whether EAW and CTD are correlated. Methods: A questionnaire modified from the Chinese Version Critical Thinking Disposition Inventory (CTDI-CV) and the Evaluation Criteria for English Argumentative Writing (ECEAW) were employed in this study. Both instruments were administered to 156 students from Grade 12. A purposive sampling of high school students was used in this study. Student EAW performance was scored by two experts based on the Evaluation Criteria for English Argumentative Writing. Results: A significant relationship was found between students' CTD and EAW abilities. Furthermore, among the eight CTD subdispositions, cognitive maturity, truth-seeking, analyticity, and justice were found to be positively correlated with EAW, and they all were found to be the main predictors of EAW proficiency among high school students. Conclusion: Zhangzhou high school students' CTDs were overall positive, and students' EAW performance correlated significantly with the overall CTD and its four subdispositions of cognitive maturity, truth-seeking, analyticity, and justice. These four subdispositions showed a significantly predictive validity on EAW performance as well.