Clostridium difficile colitis and zoonotic origins-a narrative review.

Clostridium difficile is a major cause of hospital-associated diarrhoea, and in severe cases leads to pseudomembranous colitis and toxic megacolon. The frequency of C. difficile infection (CDI) has increased in recent decades, with 453 000 cases identified in 2011 in the USA. This is related to antibiotic-selection pressure, disruption of normal host intestinal microbiota and emergence of antibiotic-resistant C. difficile strains. The burden of community-acquired CDI has been increasingly appreciated, with disease identified in patients previously considered low-risk, such as young women or patients with no prior antibiotic exposure. C. difficile has been identified in livestock animals, meat products, seafood and salads. It has been postulated that the pool of C. difficile in the agricultural industry may contribute to human CDI. There is widespread environmental dispersal of C. difficile spores. Domestic households, turf lawns and public spaces are extensively contaminated, providing a potential reservoir for community-acquired CDI. In Australia, this is particularly associated with porcine-derived C. difficile UK PCR ribotype 014/020. In this article, the epidemiological differences between hospital- and community-acquired CDI are discussed, including some emerging evidence for community-acquired CDI being a possible zoonosis.

Gastric Outlet Obstruction due to Gastrointestinal Amyloidosis.

A 64- year-old man with smoldering myeloma presented to the hospital for nausea, vomiting, and PO intolerance. Abdominal CT demonstrated massive gastric distention and collapsed proximal duodenum consistent with gastric outlet obstruction (GOO). Esophagogastroduodenoscopy demonstrated pyloric edema. Duodenal biopsies were consistent with AL amyloidosis. Given the concerns for bleeding risk and immediate need to start chemotherapy, surgery was deferred. Chemotherapy was initiated with a good clinical response. Our non-operative approach is novel, eliminates perioperative adverse events, allows for early initiation of chemotherapy, and can serve as a model for patients with GOO resulting from AL amyloidosis who are not surgical candidates.

Asymptomatic Multiple Lymphomatous Polyposis Identified during Staging Bidirectional Endoscopy of Mantle Cell Lymphoma.

Multiple lymphomatous polyposis (MLP) as an extranodal manifestation of mantle cell lymphoma (MCL) in the gastrointestinal tract is rare and not often reported in the literature. We describe the case of a 63-year-old female with asymptomatic MLP found during staging bidirectional endoscopy of MCL. The patient presented only with dyspnea, but was found on physical exam to have diffuse lymphadenopathy, and subsequent positron emission tomography (PET) CT showed extensive lymph node adenopathy consistent with lymphoma. Excisional lymph node biopsy revealed high-risk MCL. Prior to therapy, staging bidirectional endoscopy was performed, which revealed duodenal bulb polyps and diffuse polyposis in the colon. Biopsies showed atypical lymphoid infiltrate identical to the initial excisional lymph node biopsy. The patient underwent aggressive induction therapy, chemotherapy and bone marrow transplantation. Four months later, repeat colonoscopy and biopsies showed normal mucosa, and repeat PET CT showed no evidence of systemic disease. Eight months later, the patient began having symptoms consistent with cauda equina syndrome, and she was found to have leptomeningeal recurrence of MCL. In spite of other medical treatment, the patient's MCL progressed and she passed away 3 years after the initial presentation.

Rates of Microbiologically Diagnosed Infection and Pathogen Detection in Hematopoietic Stem Cell Transplant Patients.

Infections remain a significant cause of mortality in hematopoietic stem cell transplant patients. Evaluations of causes of infection are often unrevealing, and at some sites, increasing rates of antimicrobial resistance have been noticed. We performed a retrospective analysis of infection rates and microbiologic testing yield, or percent of tests ordered to diagnose an infection, in the first 100 days of 30 allogeneic and 56 autologous stem cell transplants performed at San Antonio Military Medical Center from July 2011 to April 2014. Blood stream infections were diagnosed in 11.6% with a yield of 6%. Urinary tract infections were diagnosed in 2.3% with a yield of 3%. Clostridium difficile infections were diagnosed in 9.3% and testing yield was 6%. Incidence of respiratory viruses was 5.8% with 4 rhinoviruses/enteroviruses and 1 influenza virus identified. One Proteus mirabilis urinary isolate was an extended spectrum beta-lactamase producer. Five patients, 13% of allogeneic and 4% of autologous patients, died within the first 100 days post-transplantation. History of bacteremia was present in 60% of patients who died; however, only one died due to a microbiologically diagnosed infection. Improved diagnostic tests and methods are needed to increase yield of detection of infection in hematopoietic stem cell transplant patients.

Role of primary somatosensory cortex in the coding of pain.

The intensity and submodality of pain are widely attributed to stimulus encoding by peripheral and subcortical spinal/trigeminal portions of the somatosensory nervous system. Consistent with this interpretation are studies of surgically anesthetized animals, demonstrating that relationships between nociceptive stimulation and activation of neurons are similar at subcortical levels of somatosensory projection and within the primary somatosensory cortex (in cytoarchitectural areas 3b and 1 of somatosensory cortex, SI). Such findings have led to characterizations of SI as a network that preserves, rather than transforms, the excitatory drive it receives from subcortical levels. Inconsistent with this perspective are images and neurophysiological recordings of SI neurons in lightly anesthetized primates. These studies demonstrate that an extreme anterior position within SI (area 3a) receives input originating predominantly from unmyelinated nociceptors, distinguishing it from posterior SI (areas 3b and 1), long recognized as receiving input predominantly from myelinated afferents, including nociceptors. Of particular importance, interactions between these subregions during maintained nociceptive stimulation are accompanied by an altered SI response to myelinated and unmyelinated nociceptors. A revised view of pain coding within SI cortex is discussed, and potentially significant clinical implications are emphasized.

The use of higher dose clofarabine in adults with relapsed acute lymphoblastic leukemia.

The standard dose of clofarabine is 52 mg/m2 for pediatrics and 40 mg/m2 in adults. Clofarabine dosed at 52 mg/m2 was used in adult patients with refractory ALL to maximize response before allo-HSCT. All patients had a significant response to therapy. Published pharmacokinetic analysis revealed no difference in peak plasma or intracellular concentrations at clofarabine dosed above 40 mg/m2, yet inhibition of replication in leukemia cells was only sustained over 24 hr at 55 mg/m2. Despite this, there have been no reports of high dose clofarabine used in this setting. Our experience implies that there may be a niche role for clofarabine in reducing disease burden before allo-HSCT for adults with relapsed ALL.

Analyzing the short-term effect of placebo therapy in pulmonary arterial hypertension: potential implications for the design of future clinical trials.

BACKGROUND: Placebo is commonly used in short-term randomized trials for pulmonary arterial hypertension (PAH). Currently, outcome data regarding placebo are lacking. We conducted a systematic review and performed a metaanalysis to assess its effect. METHODS: Articles were identified via a query of MEDLINE and EMBASE using the following terms: "pulmonary hypertension"; "clinical trial"; "six minute walk"; "pulmonary hemodynamic"; and "survival." A manual bibliography search of selected trials, reviews, and guidelines was performed. The inclusion criteria were as follows: randomized, placebo-controlled with data reported at baseline and at 12 to 18 weeks. Two reviewers independently abstracted: 6-min walk distance, pulmonary hemodynamic measures and frequency of death, clinical worsening, and change in New York Heart Association/World Health Organization functional class. The data were pooled using a random-effects model. RESULTS: Thirteen of the 688 articles identified met the inclusion criteria (a total of 868 placebo-treated patients). After 12 to 18 weeks, the 6-min walk distance decreased by 8.4 m (95% confidence interval [CI], -14.6 to -2.2) and pulmonary vascular resistance increased by 58.9 dyne (.) s (.) cm(-5) (95% CI, 27.6 to 90.1). Placebo-treated patients were 1.81 times more likely to experience a clinical worsening (95% CI, 1.30 to 2.53). Placebo treatment was not associated with a difference in mortality. CONCLUSIONS: Patients with PAH who receive placebo are more likely to experience clinical deteriorations. Further debate is needed regarding the design of future clinical trials. Research efforts should focus on evaluating existing medications against one another and comparing novel therapies with currently accepted ones.