Something wicked this way comes: What health care providers need to know about Candida auris.

Candida auris is a fungal pathogen that recently emerged and rapidly spread around the globe. It is now in Canada. C. auris can cause invasive disease with high mortality rates, is frequently resistant to one or more classes of antifungals, and can be difficult to identify in some clinical microbiology laboratories. C. auris can also involve prolonged colonization of patients' skin and contamination of surrounding environments, resulting in nosocomial outbreaks in hospitals and long-term care facilities. Clinicians, infection prevention and control practitioners and public health officials should be aware of how to mitigate the threat posed by this pathogen. Index cases of C. auris should be suspected in patients with invasive candidiasis and recent hospitalization in global regions where C. auris is prevalent, as well as in patients who fail to respond to empiric antifungal therapy and from whom unidentified or unusual Candida species have been isolated. If a case of C. auris infection or colonization is identified or suspected, the following should take place: notification of local public health authorities and infection prevention and control practitioners; placement of colonized or infected patients in single rooms with routine contact precautions; daily and terminal environmental disinfection with a sporicidal agent; contact tracing and screening for C. auris transmission; and referral of suspicious or confirmed isolates to provincial laboratories. Patients with symptomatic disease should be treated with an echinocandin pending the results of antifungal susceptibility testing, preferably in consultation with an infectious disease specialist. Through the vigilance of front-line health care workers and microbiologists, robust infection prevention and control practices, and local and national surveillance efforts, C. auris can be detected quickly, infections managed and transmissions prevented to protect patients in our health care system.

First reported case of multidrug-resistant Candida auris in Canada.

Candida auris is a fungal pathogen that has recently emerged as a global threat to public health. It was first described in Japan in 2009 and has since been reported in 17 countries on five continents. This case report describes the first reported case of multidrug-resistant C. auris in Canada. In May 2017, a 64-year-old individual was evaluated for chronic otitis externa. Past medical history included a recent hospitalization in India for elective oral surgery that was complicated by an odontogenic brain abscess. Upon return to Canada, the individual was admitted to a hospital for neurosurgical drainage of the brain abscess and parenteral antibiotics. Early during hospitalization, the patient was identified as a carrier of carbapenem-resistant Enterobacteriaceae and was placed on contact precautions. Also early during this hospitalization, a chronic otitis media was managed with placement of a typanostomy tube with drainage of clear fluid from the ear, which continued through the admission and after discharge to a post-neurosurgical rehabilitation facility. During outpatient follow-up, swabs of the ear discharge cultured C. auris that was resistant to fluconazole and amphotericin B. There was no clinical response to ototopical antifungal therapy. Surgical evaluation for management of the otomastoiditis is pending. There is a potential for C. auris to cause infection in health care settings. It can persist in hospital environments, has the potential for transmission and can cause invasive disease. It is difficult to identify and is often resistant to antifungal medications. The application of infection prevention and control recommendations can help prevent nosocomial transmission. It is now prudent to consider the risk of C. auris, in addition to the known risk of other antimicrobial resistant organisms, in any traveller who has been hospitalized while outside the country. When identified, contacting local public health can assist in the tracking and management of this emerging disease.

Bilateral nasal bone osteophytosis associated with short-term oral isotretinoin therapy for cystic acne vulgaris.

Bilateral 2.5 and 3.0 mm nasal bone osteophytes developed five weeks following the initiation of oral isotretinoin therapy (50 mg daily) for severe cystic acne vulgaris in a healthy 30-year-old white woman who had undergone uneventful rhinoplasty 12 years earlier. Histologically mature bone fragments were removed at surgery. Vitamin A and its analogs have been reported to cause hyperostosis of the vertebrae and long bones, but no known reports link them to nasal bone changes. Clinically significant nasal bone osteophytosis may be another adverse reaction to oral isotretinoin therapy.

Meningeal nodules with features of extranodal sinus histiocytosis with massive lymphadenopathy.

We present an unusual case of multiple intracranial meningeal nodules in a 30-year-old man. Histologically, the nodules consisted predominantly of plasma cells, histiocytes, and lymphoid cells with Russell bodies and emperipolesis. Emperipolesis may be a clue to understanding the pathogenesis of the process that has features consistent with so-called sinus histiocytosis with massive lymphadenopathy in the extranodal location.

Fatal hemorrhage from a gastric cirsoid aneurysm.

Gastric cirsoid aneurysm has been reported as a cause of massive bleeding from the stomach in less than 50 cases. It is an abnormally wide and tortuous submucosal gastric artery that is manifested clinically only subsequent to erosion and hemorrhage. A patient is described in whom the source of hemorrhage was unrecognized despite angiographic and gastroscopic examinations. Medical management was unsuccessful, and the source of fatal hemorrhage was not determined until postmortem examination.

Interobserver variation in the identification of breast carcinoma in intramammary lymphatics.

Nine surgical pathologists participated in a microscopic review of 35 cases of pT1-2 N0 M0 breast carcinoma. The pathologists outlined strict criteria for the identification of intramammary lymphatics and blood vessels and for the identification of cancerous emboli in these vascular channels. Each mastectomy case was studied by three different pathologists. All three concurred on the presence or absence of intralymphatic cancer in 12 of the 35 cases. Observers agreed on the absence of blood vessel invasion in 30 of the 35 cases. There was no consistent bias on the part of a single reviewer, either alone or with another pathologist, in identifying the emboli. We conclude that the identification of intralymphatic cancerous emboli in mastectomy specimens is not a reliably reproducible prognostic finding on which recommendation of systemic chemotherapy in stage I breast carcinoma patients can be based.

Polypoid nasal pseudolymphoma.

An unusual polypoid lesion of the nasal cavity in a 48-year-old woman with chronic obstruction consisted of aggregated nodules of benign lymphoid tissue with germinal center formation. She had no lymphadenopathy or other evidence of a systemic lymphoid disorder. To the authors' knowledge, this nonneoplastic lymphocytic proliferation, analogous to so-called "pseudolymphoma" at other sites, has not been reported heretofore in the nasal cavity or paranasal sinuses.

Lymphocytic mastopathy. An autoimmune disease of the breast?

Eight cases are reported of an unusual breast lesion consisting of dense intralobular, perilobular, and perivascular lymphocytic infiltrates associated with lobular atrophy and sclerosis. Immunologic studies on paraffin-embedded tissue (seven cases) and frozen tissue (two cases) demonstrated a predominance of B-cells and expression of HLA-DR antigen in involved lobular epithelium. The immunologic features of this lesion are reminiscent of lymphoepithelial lesions of salivary glands and other sites. A possible autoimmune pathogenesis is suggested.

Gangrenous herpetic whitlow in a human immunodeficiency virus-positive patient.

An unusual case of a gangrenous herpetic whitlow is reported. The patient, a 37-year-old man with a ten-year history of intravenous drug abuse, was antibody positive for human immunodeficiency virus. Progressive, extremely painful paronychia of the left third and fourth fingers gradually developed, which persisted despite a variety of treatment protocols, including antibiotics and radiotherapy, ultimately necessitating amputation of the distal portions of the digits. Characteristic herpes-type intranuclear inclusions within epidermal cells were identified in histologic sections of the specimen. Immunohistochemistry using rabbit antihuman herpes virus antibody confirmed the diagnosis. This apparently represents the first documented case of herpetic gangrene in an immunocompromised patient.

Beta 2-microglobulin amyloidosis (AB2M) in patients undergoing long-term hemodialysis. A new type of amyloid.

Amyloidosis has been increasingly recognized in association with renal failure and chronic hemodialysis. This report describes three patients who had long-term hemodialysis (between 7-18 years), in whom deposits developed of a new type of amyloid of beta 2-microglobulin origin. Beta 2-microglobulin amyloid (AB2M) was found in multiple organs, i.e., bone, subendocardium, gastrointestinal blood vessels, tongue, and carpal tunnel connective tissue. AB2M displayed characteristic amyloid features on conventional light and polarized microscopic examination after congo red staining. However immunostaining with anti-amyloid A protein, kappa, and lambda antisera were negative. The studied material reacted positively with beta 2-microglobulin antisera, identifying AB2M in all three cases. Ultrastructural study revealed an unusual curvi-linear fibrillar configuration. AB2M appears to be a new subtype of systemic amyloidosis secondary to renal failure and long-term hemodialysis.

A pulmonary fungus ball produced by Cladosporium cladosporioides.

A case of pulmonary fungus ball produced by Cladosporium cladosporioides is reported. The fungus occupied a cavity in the upper lobe of right lung. Invasion of the cavitary wall or adjacent pulmonary tissue by the fungus was not observed.

Purification and properties of human hepatic 3 alpha-hydroxysteroid dehydrogenase.

3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) was purified greater than 500-fold from human liver cytosol. The purification was monitored using 5 beta-[3H]dihydrocortisol (5 beta-DHF) as substrate. Electrophoretically homogeneous enzyme was obtained using a procedure that involved ammonium sulfate precipitation and three successive column chromatography steps: DEAE-cellulose, hydroxylapatite and Blue-Sepharose. The enzyme is a monomer since the native molecular weight was found to be 37,000, using a calibrated Sephadex G-75 column, and the denatured subunit molecular weight was determined to be 38,500, by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The enzyme had a pI of 5.6-5.9. The 3-ketosteroids: cortisol, testosterone, progesterone and androstenedione, were not substrates for 3 alpha-HSD indicating that a saturated 4,5 double bond was required for substrate activity. The conformation at the 5 position, however, did not influence substrate activity since 5 alpha- and 5 beta-DHF and 5 alpha-dihydrotestosterone were all reduced at similar rates. The purified enzyme preferred NADPH to NADH as a cofactor and showed a broad peak of activity in the pH range of 6.8-7.4. The apparent Km for 5 beta-DHF was 18 microM. The enzyme was markedly stabilized by 50 mM phosphate buffer containing 10 to 20% glycerol at 4 degrees C. Freezing and thawing of the enzyme resulted in a large loss of activity during early stages of the purification. This is the first report of the purification to homogeneity of 3 alpha-HSD from human tissue.

Dysgerminoma of the ovary associated with true hermaphroditism.

A dysgerminoma of the left gonad exhibiting malignant features was diagnosed at laparotomy in a 33-year-old virginal phenotypic female who had a normal menstrual history. Pathologic examination of the contralateral (right) gonad revealed an ovotestis. The nonaffected residual portion of the tumor-bearing left gonad exhibited only ovarian stroma. The ovotestis was characterized by a nodule of testicular parenchyma composed of partly hyalinized seminiferous tubules without evident spermatogenesis. The ovotestis was contiguous to normal ovarian elements, including a cystic corpus luteum and primordial follicles. Proliferative endometrium was found lining the small uterus. The findings are indicative of true hermaphroditism. The occurrence of dysgerminoma and other tumors in association with various forms of gonadl dysgenesis is discussed. To the authors' knowledge, this is the first reported case of dysgerminoma occurring in a phenotypic female hermaphrodite.

Ureteral endometriosis in post-menopausal women.

Ureteral obstruction secondary to endometriosis is an infrequently observed phenomenon, particularly in post-menopausal women. Two patients with obstructive uropathy, aged fifty-five and seventy-four, underwent ureteroplasty procedures with pathologic documentation of endometriosis. The possible pathogenetic mechanisms of ureteral endometriosis and previously reported cases are cited.

Human hepatic cortisol reductase activities: enzymatic properties and substrate specificities of cytosolic cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase(s).

The metabolism of cortisol by human liver homogenates has been studied. Cortisol delta 4-reductase and dihydrocortisol-3-oxidoreductase activities were distributed in all subcellular fractions. The products of the soluble enzymes were identified. Cortisol and 5 beta-dihydrocortisol were reduced to 3 alpha,5 beta-tetrahydrocortisol, and 5 alpha-dihydrocortisol was reduced to 3 alpha,5 alpha-tetrahydrocortisol. The soluble enzymes showed a wide range of substrate specificity. The 21 substituted cortisol derivatives were not metabolized. The apparent Km values of cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase for their substrates (cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol) all ranged from 18 to 27 microM. Dexamethasone inhibited the reduction of all of these substrates and the inhibition was abolished by 21 substitution of the dexamethasone. Testosterone was a competitive inhibitor of the reduction of cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol with a Ki ranging from 11 to 32 microM. NADPH was the preferred cofactor for the cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase. No end product inhibition was observed.

Calcification of the mitral annulus fibrosus with systemic embolization. A clinicopathologic study of 16 cases.

A review of 1343 autopsies on patients over the age of 40 years revealed 142 patients with calcification of the mitral annulus fibrosus, representing 10.6% of the studied population. Sixteen patients (11.3%) had systemic calcareous embolization. Eight patients showed clinical symptoms reflecting embolization, while the others did not. Three of the patients with clinical manifestations had been admitted to the hospital with a history of a fall and two of these, whose postmortem examination included the brain, showed focal meningitis due to embolization from an infected calcified mitral annulus fibrosus. Another three patients had been admitted to the hospital with a clinical diagnosis of cerebral vascular accident and were found to have focal ischemic necrosis or large cerebral infarcts. These were the result of either calcareous or bland embolization from a thrombus superimposed on an ulcerated calcified annulus. Eight of the 16 patients with calcareous embolization also had had sepsis, six attributable to infective endocarditis complicating the calcified mitral annulus fibrosus. This study suggests the relatively frequent occurrence of spontaneous calcareous embolization from an ulcerated calcified mitral annulus fibrosus in older adults.

Nonprolapsing atrial myxoma; clinical, echocardiographic, and angiographic correlations.

The auscultatory features typical of myxoma were absent in a patient with nonprolapsing left atrial myxoma. Angiocardiographic and echocardiographic findings including B-mode cross-sectional scanning are presented.

Cutaneous intravascular papillary endothelial hyperplasia: a benign lesion that may simulate angiosarcoma.

An example of intravascular papillary endothelial hyperplasia (Masson's pseudoangiosarcoma) of the skin of the forearm is presented. The clinical and pathologic features of the unusual lesion are described. Its benign, self-limited nature is emphasized, despite histopathologic features which may suggest the diagnosis of angiosarcoma. Appropriate therapy should therefore be directed to local excision rather than radical surgery.

Overdentures. Principles and procedures.

Although advances in methods and improved materials have contributed to better treatment results, caries and periodontal problems still remain significant threats to overdenture service life. The prevention of caries and recurrent periodontal disease thus becomes a most important aspect of postinsertion care. Undoubtedly, there are a number of successful overdenture methods. This article outlines two treatment sequences previously described by Brewer and Morrow that continue to be effective (Fig. 23). Common to most overdenture techniques is that an overdenture may be the only treatment that permits retention using the patient's last few retainable teeth. A conservative approach to root preservation still is a valid and practical measure in preventative dentistry.