Continuous exposure to chrysotile asbestos can cause transformation of human mesothelial cells via HMGB1 and TNF-α signaling.

Malignant mesothelioma is strongly associated with asbestos exposure. Among asbestos fibers, crocidolite is considered the most and chrysotile the least oncogenic. Chrysotile accounts for more than 90% of the asbestos used worldwide, but its capacity to induce malignant mesothelioma is still debated. We found that chrysotile and crocidolite exposures have similar effects on human mesothelial cells. Morphological and molecular alterations suggestive of epithelial-mesenchymal transition, such as E-cadherin down-regulation and ß-catenin phosphorylation followed by nuclear translocation, were induced by both chrysotile and crocidolite. Gene expression profiling revealed high-mobility group box-1 protein (HMGB1) as a key regulator of the transcriptional alterations induced by both types of asbestos. Crocidolite and chrysotile induced differential expression of 438 out of 28,869 genes interrogated by oligonucleotide microarrays. Out of these 438 genes, 57 were associated with inflammatory and immune response and cancer, and 14 were HMGB1 targeted genes. Crocidolite-induced gene alterations were sustained, whereas chrysotile-induced gene alterations returned to background levels within 5 weeks. Similarly, HMGB1 release in vivo progressively increased for 10 or more weeks after crocidolite exposure, but returned to background levels within 8 weeks after chrysotile exposure. Continuous administration of chrysotile was required for sustained high serum levels of HMGB1. These data support the hypothesis that differences in biopersistence influence the biological activities of these two asbestos fibers.

Metastatic Adenocarcinoma of the Bladder Presenting as Malignant Pleural Effusion: A Rare Presentation of Bladder Adenocarcinoma.

Bladder cancers rarely are non-urothelial in origin. We present here, possibly the youngest case of a 35-year-old White female presenting with shortness of breath. She was found to have a malignant pleural effusion with unknown primary, eventually confirmed with genetic testing as metastatic adenocarcinoma of the urinary bladder with brain and lung metastasis. She was scheduled for palliative chemotherapy, however, passed away before it could be started. We highlight this rare case because of its unique presentation. Owing to similarity in receptors between adenocarcinoma and enteric cancer, similar chemotherapy regimens may be used for both. Unfortunately, treatment of metastatic disease remains highly controversial and needs to be studied further if there is an actual survival benefit to this or not.

Comparing Transcatheter Aortic Valve Replacement (AVR) With Surgical AVR in Lower Risk Patients: A Comprehensive Meta-Analysis and Systematic Review.

BACKGROUND: Transcutaneous aortic valve replacement (TAVR) is a novel percutaneous procedure for severe aortic stenosis and has been recently approved by Food and Drug Administration in lower risk patients. We performed the first ever meta-analysis and literature review of clinical trials comparing both 30-day and 1-year outcomes in lower risk patients undergoing TAVR vs. surgical aortic valve replacement (SAVR, having Society of Thoracic Surgeons score < 4% or equivalent). METHODS: Using predefined selection criteria as above, 68 articles were identified. Seven eligible articles were selected after extensive review. Primary effect outcomes were 30-day and 1-year all-cause mortality using risk ratio (RR) with significant P value of < 0.05. RESULTS: A total of 4,859 subjects were included. Risk of 30-day all-cause mortality was 40.1% less in TAVR group, RR 0.59 (95% confidence interval (CI): 0.38 - 0.92, P = 0.02) with no significant heterogeneity. Six studies except Schymik et al also reported 1-year risk. This was, however, not statistically significant with a 21% decrease in the TAVR group, RR 0.79 (95% CI: 0.57 - 1.09, P = 0.15). Six studies reported 30-day risk of secondary outcomes. The risk of 30-day stroke was 36% less in TAVR group, although this was not statistically significant, RR 0.64 (95% CI: 0.38 - 1.9, P = 0.10). The risk of acute kidney injury (AKI) stage 2 and above was 56% less in post-TAVR patients, RR 0.43 (95% CI: 0.35 - 0.54, P < 0.001) with no heterogeneity. For vascular complications, RR was high in TAVR group 4.62 (95% CI: 1.42-15.18, P = 0.01). Significant heterogeneity was demonstrated though (I2 = 81). The risks for permanent pacemaker (PPM) were also higher in the TAVR group, RR 3.30 (95% CI: 2.04 - 5.33, P < 0.001) and significant heterogeneity was observed. After removing Thyregod et al and Partner 3 trial from the analysis, heterogeneity was removed, but the RR was still high 3.21 (95% CI: 2.54 - 4.068, P < 0.001). Post-operative incidence of endocarditis among TAVR patients was low but not statistically significant. The 30-day risk for infective endocarditis was RR 0.67 (95% CI: 0.13 - 3.48, P = 0.63). The 1-year risk was similarly low but not significant, RR 0.73 (95% CI: 0.28 - 1.92, P = 0.53). CONCLUSIONS: Among low risk patients, TAVR was found to be superior in short-term all-cause mortality and 1-year stroke, a result that was statistically significant for TAVR and close to significance for stroke. TAVR patients were also less likely to have post-operative bleeding and AKI stage 2 and beyond. Post-operative incidence of endocarditis among TAVR patients was low but not statistically significant. However, the rates of PPM and vascular complications are higher in TAVR patients. The results of TAVR in low risk population are thus extremely encouraging. However, the issue of long-term valve durability in this group needs further studies. Also, caution needs to be exercised while extending the indications to extremely young patients due to lack of enough studies.

Probable Vancomycin Induced Neutropenia: A Case Report.

Vancomycin has been used for a long time to manage resistant gram-positive bacterial infections. Neutropenia is an uncommon and potentially serious adverse effect associated with vancomycin use. Herein we present a case of probable vancomycin induced neutropenia which resolved with discontinuation of the antibiotic. Since blood counts are monitored routinely these days in both outpatient and inpatient setting, due consideration needs to be given to vancomycin induced neutropenia in patients who are on long term antimicrobial therapy.

A Case of Multiple Myeloma Presenting with Gastrointestinal Bleeding and Evans Syndrome.

Autoimmune events are rare in multiple myeloma (MM). Herein, we report a rare case of a patient presenting with recurrent gastrointestinal (GI) bleeding of unknown origin, also having pancytopenia eventually diagnosed as MM with Evans syndrome. This is an uncommon disorder presenting as autoimmune hemolytic anemia (AIHA) with immune thrombocytopenia purpura (ITP). A 56-year-old African American male presenting with recurrent GI bleeds and pancytopenia of unknown origin developed acute colonic diverticulitis on recurrent admissions, and sigmoid colectomy with primary anastomosis was performed. Flow cytometry with serum protein electrophoresis eventually revealed IgG MM with elevated Kappa/Lambda ratio. Bone marrow biopsy revealed 80% to 90% Kappa clonal plasma cells confirming MM. Direct antiglobulin test (DAT) was positive with pancytopenia. The patient initially showed a good response to chemotherapy with thrombocytopenia improving with intravenous (I/V) dexamethasone. DAT done after completion of initial chemotherapy was negative. However, his disease relapsed after three months with pancytopenia and DAT becoming positive again. The patient was restarted on chemotherapy for debulking, which resulted in a negative DAT again after two months, but pancytopenia did not improve. The patient eventually passed away due to subarachnoid hemorrhage. We highlight only this fourth reported case because of its unique presentation. In elderly patients with unknown cause of GI bleeding with pancytopenia, blood dyscrasias, especially MM, should be considered. Autoimmune workup if positive might warrant the use of steroids for pancytopenia, which can improve thrombocytopenia in MM with Evans syndrome but not anemia.

Cytopathologic diagnosis of Kaposi sarcoma in unusual clinical settings.

INTRODUCTION: Kaposi sarcoma (KS) is a rare disease that presents as 1 of 4 distinct clinicopathologic subtypes; however, it may present in populations outside those normally encountered. In such cases, it will be important to consider KS in the differential diagnosis, as it may mimic other neoplastic and non-neoplastic entities. MATERIALS AND METHODS: We describe 2 cases of KS, 1 in a patient not clinically fitting any of the 4 subtypes and the other in a patient with atypical presentation in human immunodeficiency virus (HIV)-associated disease. The first is an 81-year-old African American (AA) woman with a history of KS of the leg, who presented with groin lymphadenopathy and the second is a 42-year-old AA man with a known history of HIV infection, no skin lesions, and new axillary lymphadenopathy. RESULTS: Fine-needle aspiration of the groin and axillary lymph node, respectively, showed atypical spindle cells in a lymphoplasmacytic background. The spindle cells were positive for human herpesvirus-8 on the cell block and subsequent lymph node excision. In patients with HIV infection, in addition to reactive and lymphoproliferative processes, KS should be considered. In the former case, the demographic of an elderly AA woman without immunosuppression would not cause concern for systemic KS, but for a metastatic tumor or lymphoma. CONCLUSIONS: Cytology is a helpful tool in narrowing the differential diagnosis for spindle cell lesions. With a diagnosis of KS, clinicians would be able to query the clinical history for a possible etiology, such as HIV, and exclude the possibility of metastatic disease.