Resolution of diarrhea in an immunocompromised patient with chronic norovirus gastroenteritis correlates with constitution of specific antibody blockade titer

Norovirus gastroenteritis in immunocompromised hosts can result in a serious and prolonged diarrheal illness. We present a case of chronic norovirus disease during rituximab-bendamustine chemotherapy for non-Hodgkin's lymphoma. We show for the first time a correlation between norovirus strain-specific antibody blockade titers and symptom improvement in an immunocompromised host

The origin of multicellularity in cyanobacteria

Background: Cyanobacteria are one of the oldest and morphologically most diverse prokaryotic phyla on our planet. The early development of an oxygen-containing atmosphere approximately 2.45 - 2.22 billion years ago is attributed to the photosynthetic activity of cyanobacteria. Furthermore, they are one of the few prokaryotic phyla where multicellularity has evolved. Understanding when and how multicellularity evolved in these ancient organisms would provide fundamental information on the early history of life and further our knowledge of complex life forms. Results: We conducted and compared phylogenetic analyses of 16S rDNA sequences from a large sample of taxa representing the morphological and genetic diversity of cyanobacteria. We reconstructed ancestral character states on 10,000 phylogenetic trees. The results suggest that the majority of extant cyanobacteria descend from multicellular ancestors. Reversals to unicellularity occurred at least 5 times. Multicellularity was established again at least once within a single-celled clade. Comparison to the fossil record supports an early origin of multicellularity, possibly as early as the “Great Oxygenation Event” that occurred 2.45 - 2.22 billion years ago. Conclusions: The results indicate that a multicellular morphotype evolved early in the cyanobacterial lineage and was regained at least once after a previous loss. Most of the morphological diversity exhibited in cyanobacteria today —including the majority of single-celled species— arose from ancient multicellular lineages. Multicellularity could have conferred a considerable advantage for exploring new niches and hence facilitated the diversification of new lineages

Infections in Patients on BCR-ABL Tyrosine Kinase Inhibitor Therapy: Cases and Review of the Literature

The introduction of BCR-ABL-tyrosine kinase inhibitors (TKI) for treatment of hematologic malignancies has made a significant impact on patient outcome. Contingent upon their targeted and off-target activity, therapy-associated infectious complications may occur. We present a case of cytomegalovirus pneumonitis and a case of adenovirus hemorrhagic cystitis in two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia on BCR-ABL TKI treatment and review the literature to summarize the infectious complications based on clinical data. As life-threatening infections may occur, treating physicians should maintain a heightened awareness in patients treated with BCR-ABL TKIs. Based on the frequent reports of hepatitis B virus (HBV) reactivation under the treatment BCR-ABL TKIs, screening for and prophylactic therapy of chronic HBV infection should be considered. Similarly, patients would benefit from screening for and treatment of latent tuberculosis

Three Months of Weekly Rifapentine Plus Isoniazid for Latent Tuberculosis Treatment in Solid Organ Transplant Candidates

BACKGROUND: Isoniazid daily for 9 months is the recommended regimen for latent tuberculosis infection (LTBI) in solid organ transplant (SOT) candidates, but its use is controversial, due to reports of hepatotoxicity and low treatment completion rates. A 12-week course of once weekly directly observed therapy (DOT) with isoniazid plus rifapentine (3HP) is a new LTBI treatment regimen. Tolerability and safety data of 3HP LTBI treatment in SOT candidates are limited. METHODS: Twelve consecutive SOT candidates who underwent DOT with 3HP for LTBI at Westchester Medical Center, Valhalla, New York, USA, between January 2013 and August 2016 were prospectively evaluated for tolerability and safety of 3HP. The diagnosis of LTBI was made in a person with a positive interferon-gamma release test, without a history of previously treated active or latent tuberculosis infection, and without signs, symptoms, or radiographic evidence of active tuberculosis. Patients were followed up 1 month after treatment completion and at routine follow-up visits with their transplant providers. RESULTS: Eleven patients were men, and the median age was 60 years (range 44-72). Eight patients were liver, and four kidney transplant candidates. The median Model for End-Stage Liver Disease (MELD score) was 17 (range 10-31). All patients completed treatment. Only a single patient developed transaminitis greater than twice the baseline value. Three patients underwent liver transplantation. None of them developed tuberculosis at 9, 22, or 40 months following transplantation. CONCLUSION: Directly observed 3HP LTBI treatment was not associated with hepatotoxicity, even in patients with higher MELD scores. Further studies are needed to confirm the safety and efficacy of this LTBI treatment regimen in the SOT population

Intestinal Pathophysiological and Microbial Changes in Sickle Cell Disease: Potential Targets for Therapeutic Intervention

There is a large therapeutic gap in the treatment of sickle cell disease (SCD). Recent studies demonstrated the presence of pathophysiological and microbial changes in the intestine of patients with SCD. The intestinal microbes have also been found to regulate neutrophil ageing and possible basal activation of circulating neutrophils. Both aged and activated neutrophils are pivotal for the pathogenesis of vaso-occlusive crisis in SCD. In this paper, we will provide an overview of the intestinal pathophysiological and microbial changes in SCD. Based on these changes, we will propose therapeutic approaches that could be investigated for treating SCD

A Contemporary Review of Clostridioides Difficile Infections in Patients with Haematologic Diseases

Clostridioides (Clostridium) difficile (C. difficile) infection is one of the most common causes of increased morbidity and mortality. Approximately 500 000 C. difficile infections (CDIs) occur each year in the United States, and they result in more than 29 000 deaths. Patients with haematologic diseases are at a higher risk for this infection due to frequent hospitalization and exposure to treatment-associated risk factors. Whilst several currently available antimicrobial agents offer resolution, recurrence of infection remains a major concern. Recent advancement in deciphering C. difficile virulence mechanisms and identification of its allies in contributing to the infection has led to the development of alternative treatment strategies. Here, we will provide a contemporary discussion of how major risk factors in haematologic diseases, such as immunosuppression, chemoradiation, use of antibiotic, proton pump inhibitor and opioid, and deficiency in butyrate and antimicrobial peptides contribute to C. difficile infection. Next, we will highlight different approaches to control and mitigate this infection such as antibiotic stewardship and faecal microbiota transplantation. Finally, we will explore several emerging treatments such as use of pre- and probiotics, immunotherapy and microbiome-sparing agents

Invasive non-typhoidal Salmonella in sickle cell disease in Africa: is increased gut permeability the missing link?

Abstract Non-typhoidal Salmonella usually induces self-limiting gastroenteritis. However, in many parts of Africa, especially in individuals who are malnourished, infected with malaria, or have sickle cell disease, the organism causes serious and potentially fatal systemic infections. Since the portal of entry of non-typhoidal Salmonella into the systemic circulation is by way of the intestine, we argue that an increased gut permeability plays a vital role in the initiation of invasive non-typhoidal Salmonella in these patients. Here, we will appraise the evidence supporting a breach in the intestinal barrier and propose the mechanisms for the increased risks for invasive non-typhoidal Salmonella infections in these individuals

Temporal Trends in the Incidence of Staphylococcus Aureus Bacteremia in Olmsted County, Minnesota, 1998 to 2005: A Population-Based Study

Background. There is a paucity of population-based studies on Staphylococcus aureus bacteremia (SAB) in the United States. We determined the incidence of and trends in SAB in Olmsted County, Minnesota, over an 8-year period. Methods. A retrospective, population-based, cohort study was done to evaluate the initial episodes of SAB occurring in adult residents of Olmsted County, Minnesota, from 1 January 1998 through 31 December 2005, using the microbiology databases at Mayo Clinic and Olmsted Medical Center in Rochester, Minnesota. Results. Of 247 evaluable adult patients with SAB who were included in the incidence calculation, 143 (57.9%) were males, and the median age was 72.1 years (range, 19.5-98.5 years). Episodes of bacteremia were classified according to acquisition type: 58 (23.5%) were nosocomial (N-SAB), 145 (58.7%) were healthcare-associated (HCA-SAB), and 44 (17.8%) were community-acquire d (CA-SAB). Methicillin-resistant S. aureus (MRSA) constituted 31.6% of the cases. No community-acquired MRSA bacteremia was noted. The age-adjusted incidence of SAB was 28.3 episodes/100,000 person-years for females and 53.5 episodes/100,000 person-years for males, with an age- and sex-adjusted rate of 38.2 episodes/100,000 person-years. The age- and sex-adjusted incidence of NSAB, HCA-SAB, and CA-SAB was 9.0, 22.6, and 6.6 episodes/100,000 person-years, respectively. The age- and sexadjusted incidence of methicillin-susceptible S. aureus was 25.4 episodes/100,000 person-years, and that of MRSA was 12.4 episodes/100,000 person-years. Overall, the incidence rate increased with age but not over the calendar year. The exception was MRSA bacteremia, which increased at a rate of 19.8% (standard error, ± 5.5%) per year during the study. Conclusions. The incidence of SAB in adults remained stable in Olmsted County, Minnesota, from 1998 to 2005, but the proportion of episodes due to MRSA significantly increased over the 8-year period