A Case of Muir-Torre Syndrome.

Muir-Torre syndrome (MTS) is an autosomal dominant condition characterized by dermatological tumors along with visceral malignancies. The dermatological manifestations include recurrent sebaceous adenomas and keratoacanthomas. The commonly seen visceral malignancies are colorectal, gynecological, and urological. It is a variant of hereditary non-polyposis colorectal carcinoma syndrome (HNPCC). The underlying genetic mechanism is germline mutations in the DNA mismatch repair (MMR) genes leading to microsatellite instability (MSI), conferring an increased risk of developing malignancies. This is a case of a 57-year-old male patient with a history of colon cancer diagnosed at age 32 and multiple sebaceous adenomas. The patient also has a strong family history of cancer. They were referred to oncology after the immunohistochemical staining of a sebaceous adenoma showed loss of expression for MSH2 and MSH6. Next-generation sequencing identified a mutation in the MSH2 gene. These patients require genetic testing, counseling, and close follow-up with regular screening for cancer.

Characteristics and comparative clinical outcomes of prisoner versus non-prisoner populations hospitalized with COVID-19.

Prisons in the United States have become a hotbed for spreading COVID-19 among incarcerated individuals. COVID-19 cases among prisoners are on the rise, with more than 143,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with COVID-19. An observational study of all patients hospitalized with COVID-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were used to investigate primary outcomes. Of the 706 hospitalized COVID-19 patients (mean age 66.7 ± 16.1 years, 57% males, and 44% black), 108 were prisoners and 598 were non-prisoners. Compared to non-prisoners, prisoners were more likely to present with fever, tachypnea, hypoxemia, and markedly elevated inflammatory markers. Prisoners were more commonly admitted to the intensive care unit (ICU) (26.9% vs. 18.7%), required vasopressors (24.1% vs. 9.9%), and intubated (25.0% vs. 15.2%). Prisoners had higher unadjusted inpatient mortality (29.6% vs. 20.1%) and 30-day mortality (34.3% vs. 24.6%). In the adjusted models, prisoner status was associated with higher in-hospital death (odds ratio, 2.32; 95% confidence interval (CI), 1.33 to 4.05) and 30-day mortality (hazard ratio, 2.00; 95% CI, 1.33 to 3.00). In this cohort of hospitalized COVID-19 patients, prisoner status was associated with more severe clinical presentation, higher rates of ICU admissions, vasopressors requirement, intubation, in-hospital mortality, and 30-day mortality.

Cutaneous Fusariosis in a Patient with Job's (Hyper-IgE) Syndrome.

Fusarium is a filamentous fungus that is ubiquitous in nature and can cause severe opportunistic infections in immunocompromised hosts. The association between Fusarium and hyper-IgE syndrome is exceedingly rare and has only been documented in a single report previously. A 44-year-old male, working as marijuana grower, with prior diagnosis of hyper-IgE syndrome and recurrent infections presented with enlarging right knee ulcer that did not respond to antimicrobial treatment. The patient was diagnosed with cutaneous fusariosis, confirmed with punch biopsy and positive wound cultures. The patient was managed with extended antifungal therapy (i.e., posaconazole) and surgical debridement resulting in remarkable improvement with wound healing leaving a pale scar. Fusarium should be considered in differential for cutaneous and invasive fungal infections in presence of cutaneous manifestations. Exposure to Cannabis plants is a noticeable risk factor. Multimodal approach involving systemic antifungals and wound debridement is essential for favorable outcome. Posaconazole was demonstrated to be a highly efficacious antifungal choice.

Bilateral Hydronephrosis From Retroperitoneal Fibrosis.

Retroperitoneal fibrosis (RPF) is a rare condition characterized by fibroinflammatory tissue infiltrating and compressing retroperitoneal structures. While mostly idiopathic (idiopathic retroperitoneal fibrosis or IRF), RPF is frequently associated with certain drugs, infections, and malignancies. It is thought to be immune-mediated because of response to steroids and RPF is commonly seen with other autoimmune diseases, especially IgG4-related disease (IgG4-RD). IRF is also a part of the chronic aortitis syndromes and the presence of aortic aneurysms is another characteristic of this disease. A 63-year old woman presented with left-sided flank pain. Computed tomography (CT) scan showed left hydronephrosis from compression of the ureter by a retroperitoneal mass. A thoracoabdominal aneurysm was also noted. A [18F]- fluorodeoxyglucose positron emission tomography (FDG-PET) scan showed hypermetabolism in the mass, with no abnormally increased activity noted elsewhere. Within four months, the mass enlarged to involve the right ureter as well, leading to right hydronephrosis. She required bilateral ureteral stents and aneurysm repair. Biopsy of the mass showed dense fibrosis with a mononuclear cell infiltrate. The histology of the aneurysm specimen showed chronic periaortic inflammation. Laboratory investigations were significant for elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), with no evidence of monoclonal gammopathy. She was referred to the rheumatology clinic to receive steroid treatment for IRF. IRF commonly involves the ureters and is diagnosed on CT scans during a workup for obstructive uropathy. The treatment is high dose steroids, while in resistant cases, other immunosuppressants have been used. The presentation of a patient with IRF can commonly mimic that of urinary calculi and malignancy. While rare, IRF should not be forgotten when evaluating a patient for obstructive uropathy.

Culture and Characterization of Oral Mucosal Epithelial Cells on a Fibrin Gel for Ocular Surface Reconstruction.

AIM OF THE STUDY: To develop a clinical grade fibrin gel for the culture of oral mucosal epithelial cells (OMEC) intended for ocular surface reconstruction in the treatment of limbal stem cell deficiency (LSCD). MATERIALS AND METHODS: Transparent fibrin gels composed of fibrinogen and thrombin were developed for the culture of epithelial cells. Oral mucosa was harvested from the buccal region of healthy volunteers and cultured as explants on fibrin gels. Tranexamic acid (TA), a clinically approved anti-fibrinolytic agent was added to prevent the fibrin gel from digesting due to cellular activity. The gels were stained for p63α (as a marker of poorly differentiated epithelial cells), CK19, CK13 and CK3 (expressed by OMEC). Epithelial cell stratification was observed using hematoxylin-eosin staining. RESULTS: Addition of TA prevented gels from dissolving during the culture period. OMEC proliferated on the fibrin gel and attained confluence over a 2-week period (±2 d) and exhibited a typical epithelial, cobblestone morphology. Basal OMEC exhibited positive staining for p63α while the superficial cells exhibited positive staining for CK3. The cells expressed a strong immunoreactivity for CK19 and CK13 suggesting that they retained a normal oral epithelial phenotype. CONCLUSION: Fibrin gels, maintained in the presence of TA, to control the rate of substrate degradation, provide a more robust yet transparent substrate for the culture and transplantation of cultured OMEC. The fibrin gels are easily standardized, the components commercially available, and produced from clinically approved materials. The resulting stratified OMEC-derived epithelium displays characteristics similar to that of a human cornea, e.g. CK3 expression. The conventional dependence on a murine feeder layer for support of epithelial cells is unnecessary with this technique and hence, provides for an attractive alternative for treatment of LSCD.

Advanced imaging and tissue engineering of the human limbal epithelial stem cell niche.

The limbal epithelial stem cell niche provides a unique, physically protective environment in which limbal epithelial stem cells reside in close proximity with accessory cell types and their secreted factors. The use of advanced imaging techniques is described to visualize the niche in three dimensions in native human corneal tissue. In addition, a protocol is provided for the isolation and culture of three different cell types, including human limbal epithelial stem cells from the limbal niche of human donor tissue. Finally, the process of incorporating these cells within plastic compressed collagen constructs to form a tissue-engineered corneal limbus is described and how immunohistochemical techniques may be applied to characterize cell phenotype therein.

Production and validation of a good manufacturing practice grade human fibroblast line for supporting human embryonic stem cell derivation and culture.

INTRODUCTION: The development of reproducible methods for deriving human embryonic stem cell (hESC) lines in compliance with good manufacturing practice (GMP) is essential for the development of hESC-based therapies. Although significant progress has been made toward the development of chemically defined conditions for the maintenance and differentiation of hESCs, efficient derivation of new hESCs requires the use of fibroblast feeder cells. However, GMP-grade feeder cell lines validated for hESC derivation are not readily available. METHODS: We derived a fibroblast cell line (NclFed1A) from human foreskin in compliance with GMP standards. Consent was obtained to use the cells for the production of hESCs and to generate induced pluripotent stem cells (iPSCs). We compared the line with a variety of other cell lines for its ability to support derivation and self-renewal of hESCs. RESULTS: NclFed1A supports efficient rates (33%) of hESC colony formation after explantation of the inner cell mass (ICM) of human blastocysts. This compared favorably with two mouse embryonic fibroblast (MEF) cell lines. NclFed1A also compared favorably with commercially available foreskin fibroblasts and MEFs in promoting proliferation and pluripotency of a number of existing and widely used hESCs. The ability of NclFed1A to maintain self-renewal remained undiminished for up to 28 population doublings from the master cell bank. CONCLUSIONS: The human fibroblast line Ncl1Fed1A, produced in compliance with GMP standards and qualified for derivation and maintenance of hESCs, is a useful resource for the advancement of progress toward hESC-based therapies in regenerative medicine.