Changing epidemiology of rare mould infections: implications for therapy

There has been an increase in rare mould infections in recent decades. These infections have been reported primarily in severely immunocompromised patients. The emergence of these organisms is multifactorial and can be related to more intense immunosuppression, the prolonged survival of patients who have what were previously fatal diseases, and the selective pressure of broad spectrum antifungal agents used for prophylaxis or therapy. Among these rare mould infections, the Zygomycetes are the most commonly encountered, and in some institutions the increase in these organisms appears to be associated with the use of voriconazole. Aspergillus terreus, a species that is resistant to amphotericin B, and less frequently, A. ustus and A. lentulus, have been noted increasingly as causes of invasive aspergillosis in tertiary care centres in the US. Several species of Scedosporium with innate resistance to many antifungal agents have emerged as major causes of disseminated mould infections that are frequently very difficult to treat. Among patients who have haematological malignancies, are neutropenic or have received a haematopoietic stem cell transplant, infections due to Fusarium species respond poorly to many antifungal agents. Dematiaceous, or brown-black, fungi, most often associated with chronic localised infections, are now increasingly reported as a cause of disseminated infection in immunosuppressed hosts.Concomitant with the increased number of infections with these rare moulds, several new mould-active antifungal agents have been developed. The new expanded spectrum azole, voriconazole, has changed our approach to moulds such as S.apiospermum, Fusarium species and A. terreus that are amphotericin B resistant. Posaconazole, the most recently approved expanded spectrum azole, is the first drug in the azole class to show activity against the Zygomycetes and has proven extremely useful for step-down therapy after initial treatment with amphotericin B. It is not known whether posaconazole is effective as primary therapy for zygomycosis; the use of this agent for that purpose awaits clinical trials with the recently developed intravenous formulation of posaconazole.     

Incremental value of live/real time three-dimensional transthoracic echocardiography in the assessment of left ventricular thrombi

This is a case series on three adult patients who contain left ventricular (LV) thrombus and the incremental benefits of live/real time three-dimensional transthoracic echocardiography (3DTTE) in comparison to two-dimensional transthoracic echocardiography (2DTTE) in evaluating LV thrombi. These cases illustrate that 3DTTE is of additional benefit by demonstrating the following: (1) cropping of a single 3DTTE apical dataset may be enough to provide comprehensive assessment of the LV in a timely manner even without breath holding in a not fully cooperative patient (2) it identifies the exact point of attachment of the thrombus to the left ventricular wall, (3) helps to delineate the absence or presence of focal echolucent areas within thrombi indicative of the presence and extent of clot lysis, which may have potential therapeutic and prognostic implications, and (4) provides more accurate assessment of thrombus mobility which has prognostic indications.     

Performance of polygenic risk scores for cancer prediction in a racially diverse academic biobank

PurposeGenome-wide association studies have identified hundreds of single nucleotide variations (formerly single nucleotide polymorphisms) associated with several cancers, but the predictive ability of polygenic risk scores (PRSs) is unclear, especially among non-Whites.MethodsPRSs were derived from genome-wide significant single-nucleotide variations for 15 cancers in 20,079 individuals in an academic biobank. We evaluated the improvement in discriminatory accuracy by including cancer-specific PRS in patients of genetically-determined African and European ancestry.ResultsAmong the individuals of European genetic ancestry, PRSs for breast, colon, melanoma, and prostate were significantly associated with their respective cancers. Among the individuals of African genetic ancestry, PRSs for breast, colon, prostate, and thyroid were significantly associated with their respective cancers. The area under the curve of the model consisting of age, sex, and principal components was 0.621 to 0.710, and it increased by 1% to 4% with the inclusion of PRS in individuals of European genetic ancestry. In individuals of African genetic ancestry, area under the curve was overall higher in the model without the PRS (0.723-0.810) but increased by <1% with the inclusion of PRS for most cancers.ConclusionPRS moderately increased the ability to discriminate the cancer status in individuals of European but not African ancestry. Further large-scale studies are needed to identify ancestry-specific genetic factors in non-White populations to incorporate PRS into cancer risk assessment.     

A puzzling case of anemia

BACKGROUND: Iron deficiency anemia in adults is most frequently due to chronic blood loss. When the clinical course is complicated by sudden, severe declines in Hb concentration, the cause, nature, and lo- cation of bleeding may require an extensive clinical evaluation. CASE REPORT: A 39-year-old woman was admitted for management of refractory hypoparathyroidism related to total thyroidectomy for Graves' disease. Two weeks before admission, her Hb level was 7.0 g per dL. Despite transfusion with four units of RBCs during this interval, her admission Hb level was 5.7 g per dL. There was no evidence of blood loss or hemolysis. Laboratory values were consistent with an iron-deficient state. The patient's hospital course included repeated instances of sharp Hb drop and appropriate but unsustained response to RBC transfusion. Extensive work-up identified no occult source of bleeding. Clinical suspicion raised the possibility of self-inflicted blood loss. The patient subsequently admitted to repeatedly drawing blood from her indwelling catheter and discarding it in the lavatory. CONCLUSION: Munchausen syndrome should be considered in cases of unexplained anemia, especially in the target demographic group: young, female, healthcare professionals. Early diagnosis may prevent morbidity, multiple hospitalizations, and the risk of invasive diagnostic procedures.     

Carcinoma Gall Bladder with Bouveret’s Syndrome: A Rare Cause of Gastric Outlet Obstruction

We describe a case of bouveret’s syndrome associated with carcinoma gall bladder. This is probably the second reported case of such an association. Computed tomography detected the calculus in the duodenum but endoscopy could not retrieve it. Open gastrojejunostomy and stone retrieval was done.     

Live/real time three-dimensional transthoracic echocardiographic identification of quadricuspid aortic valve

We describe an adult in whom live/real time three-dimensional echocardiography was able to make a definite diagnosis of a quadricuspid aortic valve which was misdiagnosed as bicuspid by live two-dimensional transthoracic echocardiography (2DTTE).