Early diagnosis and successful long-term management of a rare, severe lysosomal acid lipase deficiency/Wolman disease patient: Infancy to age five.

Background: This report describes a unique case of long-term survival of a young girl who was diagnosed with severe, rapidly progressive lysosomal acid lipase deficiency (LAL-D; historically "Wolman disease") at three months of age and began receiving therapeutic interventions at four months of age. This disease involves rapidly progressive multisystemic impairments and limited survival (6-12 months) without treatment. Methods: Case report taking into account clinical aspects and patient management including a semi-structured interview with the main family caregiver. Results: Presentation at two months of age: severe malnutrition and chronic diarrhea; hypoalbuminemia; low iron, vitamin A, and vitamin D levels; high triglyceride levels; profound anemia; thrombocytopenia; adrenal calcifications; and mild hepatosplenomegaly. Enzyme replacement therapy (ERT) with sebelipase alfa, parenteral nutrition, and a low-fat diet began at age four months. The patient has received sebelipase alfa for >5 years with good tolerability and is thriving, with a body mass index of 16.35 kg/m2 (80th percentile) despite a stature delay (height <3rd percentile), and mild developmental delay. Optimal medical management requires that family caregivers and health professionals have the knowledge and skills to provide appropriate care and supports multidisciplinary teams through transfer of knowledge to all stakeholders. Effective coordination of services and activities related to child health and development, including navigation of administrative and financial barriers, is also imperative. Conclusions: Formerly fatal in untreated infants, severe LAL-D, when diagnosed early, can be promptly and effectively treated by combining sebelipase alfa ERT, modified diet, involvement of family caregivers, and multidisciplinary team collaboration.

Simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient: A case report and literature review.

Advances in solid organ transplantation have improved the survival of end-stage organ disease at the expense of an increased risk for opportunistic infections. Unusual clinical presentations and the possibility of concurrent infections make diagnosing invasive fungal infection (IFI) more difficult. Here, we present a case of simultaneous vertebral infection caused by Coccidioides immitis-posadasii and subcutaneous phaeohyphomycosis due to Nigrograna mackinnonii in a kidney transplant recipient. The diagnosis of both infections required invasive procedures to obtain tissue and a high index of suspicion that more than one IFI could be present. A multidisciplinary team approach for the management of immunocompromised patients with suspected or diagnosed IFI is warranted.

Secular trends in incidence of invasive beta-hemolytic streptococci and efficacy of adjunctive therapy in Quebec, Canada, 1996-2016.

OBJECTIVES: To examine secular changes in the incidence of invasive beta-hemolytic streptococcal infections, and to assess the efficacy of immunoglobulins and clindamycin as adjunctive therapies in the management of Streptococcus pyogenes infections. METHODS: Retrospective cohort study of all cases of invasive group A (GAS), B (GBS), C or G (GCGS) streptococcal infections managed in a Canadian tertiary center from 1996-2016. Population incidence was measured for diabetics and non-diabetics. Adjusted odds ratios (AOR) and their 95% confidence intervals (CI) were calculated by logistic regression. RESULTS: 741 cases were identified (GAS: 249; GBS: 304; GCGS: 188). While the incidence of invasive GAS infections fluctuated with no clear trend, incidence of invasive GBS and GCGS increased over time and were 8.4 and 6.3 times higher in diabetics. Mortality of invasive GAS infections decreased from 16% (6/37) in 1996-2001 to 4% (4/97) in 2011-15. Among patients with GAS infections, clindamycin administered concomitantly with a beta-lactam within 24 hours of admission decreased mortality (AOR: 0.04, 95%CI: 0.003-0.55, P = 0.02. Immunoglobulins had no such effect (AOR: 1.66, 95%CI: 0.16-17.36, P = 0.67). The protective effect of clindamycin was similar in patients with pneumonia/empyema compared to all others. CONCLUSION: Incidence of GBS and GCGS infections increased due to an expansion of the high-risk population (elderly diabetics), but also rose in non-diabetics. No such secular change was seen for invasive GAS infections. The decrease in mortality in patients with invasive GAS infections presumably reflects better case-management. Adjunctive clindamycin reduced mortality in invasive GAS infections; immunoglobulins did not, but power was limited. The highest mortality was seen in patients with GAS pneumonia/empyema, for whom clindamycin was protective but underused.

Bezlotoxumab for the prevention of Clostridium difficile recurrence.

INTRODUCTION: Clostridium difficile infection is a major economic and clinical burden, due to its high frequency of recurrence. Currently recommended treatments are not efficient for prevention and may contribute to the risk of recurrent infection. In recent years, research has focused on strategies to lessen this risk. Bezlotoxumab is a monoclonal antibody that prevents recurrences of C. difficile infection through the antagonism of toxin B. Areas covered: In this review, the authors discuss the burden of C. difficile infection and its recurrences, the mechanisms underlying the recurrences, and current C. difficile treatments. They subsequently analyze the strategic therapeutic rationale for bezlotoxumab use, as well as the supporting clinical evidence. Expert opinion: Bezlotoxumab is an attractive solution for reducing the unacceptable level of recurrence that occurs with the currently recommended C. difficile treatments and other alternative therapies under consideration. Even though bezlotoxumab has not been tested in large-scale trials exclusively in cases of already established recurrent C.difficile infection (rCDI), it has an advantage over current treatments in that it does not interfere with the patient's gut flora while directly neutralizing the key virulence factor. Although cost remains an important factor against its widespread use, simpler administration, fewer side-effects, and better social acceptability justify its consideration for treating rCDI.