Namita Singh

Fecal Microbiota Transplant for Treatment of Clostridium difficile Infection in Immunocompromised Patients

OBJECTIVES:Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients.METHODS:A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT.RESULTS:Cases included adult (75) and pediatric (5) patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3–46 months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19), oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT, but two patients developed unrelated infections and five had self-limited diarrheal illness in which no causal organism was identified. One patient had a superficial mucosal tear caused by the colonoscopy performed for the FMT, and three patients reported mild, self-limited abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy related to course of UC >100 days after FMT.CONCLUSIONS:This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs. Importantly, there were no related infectious complications in these high-risk patients.

Gabapentin for the treatment of pain in guillain-barré syndrome: a double-blinded, placebo-controlled, crossover study.

Pain syndromes of Guillain-Barré are neuropathic as well as nociceptive in origin. We aimed to evaluate the therapeutic efficacy of gabapentin in relieving the bimodal nature of pain in Guillain-Barré syndrome in a randomized, double-blinded, placebo-controlled, crossover study in 18 patients admitted to the intensive care unit for ventilatory support. Patients were assigned to receive either gabapentin (15 mg · kg−1 · d−1 in 3 divided doses) or matching placebo as initial medication for 7 days. After a 2-day washout period, those who previously received gabapentin received placebo, and those previously receiving placebo received gabapentin as in the initial phase. Fentanyl 2 &mgr;g/kg was used as a rescue analgesic on patient demand or when the pain score was >5 on a numeric rating scale of 0–10. The numeric rating score, sedation score, consumption of fentanyl, and adverse effects were noted, and these observed variables were compared. The numeric pain score decreased from 7.22 ± 0.83 to 2.33 ± 1.67 on the second day after initiation of gabapentin therapy and remained low during the period of gabapentin therapy (2.06 ± 0.63) (P < 0.001). There was a significant decrease in the need for fentanyl from Day 1 to Day 7 during the gabapentin therapy period (211.11 ± 21.39 to 65.53 ± 16.17 [&mgr;g]) in comparison to the placebo therapy period (319.44 ± 25.08 to 316.67 ± 24.25 [&mgr;g]) (P < 0.001).

Enhanced saccharification of rice straw and hull by microwave–alkali pretreatment and lignocellulolytic enzyme production

In this study, statistical design of experiments was employed to plan experiments and optimize the microwave-alkali pretreatment of rice straw and hulls. Process parameters important in pretreatment of biomass were identified by a Plackett-Burman design and the parameters with significant effects were optimized using a box-behnken design (BBD). Experimental results show that alkali concentration (AC), irradiation time (IT) and substrate concentration (SC) were main factors governing the saccharification of rice straw and hulls. Optimum conditions of pretreatment were AC 2.75%, IT 22.50 min and SC 30 g/L, as optimized by BBD. The growth and production of lignocellulolytic enzymes from Aspergillus heteromorphus, solid state fermentation (SSF) was performed using rice straw and hulls pretreated under optimum conditions. Cellulases and xylanase reached the highest enzyme activity at 6th day of fermentation while maximum manganese peroxidase (MnP) and laccase activity occurred at 12th day.

Fecal Microbial Transplant Effect on Clinical Outcomes and Fecal Microbiome in Active Crohn’s disease

Background:Crohns disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbial transplant (FMT) is a potential therapeutic option for individuals with CD based on the hypothesis that changing the fecal dysbiosis could promote less intestinal inflammation. Methods:Nine patients, aged 12 to 19 years, with mild-to-moderate symptoms defined by Pediatric Crohns Disease Activity Index (PCDAI of 10–29) were enrolled into a prospective open-label study of FMT in CD (FDA IND 14942). Patients received FMT by nasogastric tube with follow-up evaluations at 2, 6, and 12 weeks. PCDAI, C-reactive protein, and fecal calprotectin were evaluated at each study visit. Results:All reported adverse events were graded as mild except for 1 individual who reported moderate abdominal pain after FMT. All adverse events were self-limiting. Metagenomic evaluation of stool microbiome indicated evidence of FMT engraftment in 7 of 9 patients. The mean PCDAI score improved with patients having a baseline of 19.7 ± 7.2, with improvement at 2 weeks to 6.4 ± 6.6 and at 6 weeks to 8.6 ± 4.9. Based on PCDAI, 7 of 9 patients were in remission at 2 weeks and 5 of 9 patients who did not receive additional medical therapy were in remission at 6 and 12 weeks. No or modest improvement was seen in patients who did not engraft or whose microbiome was most similar to their donor. Conclusions:This is the first study to demonstrate that FMT for CD may be a possible therapeutic option for CD. Further prospective studies are required to fully assess the safety and efficacy of the FMT in patients with CD.

Biosorption optimization of lead(II), cadmium(II) and copper(II) using response surface methodology and applicability in isotherms and thermodynamics modeling.

The present study was carried out to optimize the various environmental conditions for biosorption of Pb(II), Cd(II) and Cu(II) by investigating as a function of the initial metal ion concentration, temperature, biosorbent loading and pH using Trichoderma viride as adsorbent. Biosorption of ions from aqueous solution was optimized in a batch system using response surface methodology. The values of R(2) 0.9716, 0.9699 and 0.9982 for Pb(II), Cd(II) and Cu(II) ions, respectively, indicated the validity of the model. The thermodynamic properties DeltaG degrees , DeltaH degrees , DeltaE degrees and DeltaS degrees by the metal ions for biosorption were analyzed using the equilibrium constant value obtained from experimental data at different temperatures. The results showed that biosorption of Pb(II) ions by T. viride adsorbent is more endothermic and spontaneous. The study was attempted to offer a better understating of representative biosorption isotherms and thermodynamics with special focuses on binding mechanism for biosorption using the FTIR spectroscopy.

Early infliximab trough levels are associated with persistent remission in pediatric patients with inflammatory bowel disease.

Background:Low infliximab (IFX) trough levels and high anti-infliximab antibodies (ATI) levels are associated with loss of response to IFX. Optimizing IFX levels to maintain target concentrations before loss of response may improve long-term efficacy. We hypothesized that trough levels at week 14 are predictive of IFX durability. Methods:A prospective observational cohort of pediatric patients with inflammatory bowel disease initiating IFX had IFX and ATI levels drawn at weeks 14 and 54. Primary outcome was week 54 persistent remission (PR), defined as clinical remission without IFX dose intensification. Univariate analyses tested associations of week 14 IFX (IFX14) and ATI (ATI14) levels, clinical and laboratory data with week 54 outcomes. Receiver operating curve analysis and positive and negative predictive values for IFX14 cut-off points were examined. Results:Of 58 patients enrolled, 8 (13%) stopped IFX before week 14 and 4 discontinued IFX between weeks 14 and 54. IFX14 level (P = 0.03), baseline C-reactive protein (CRP) level (P = 0.01), and week 14 CRP (CRP14) level (P = 0.0001) were associated with PR. A model with IFX14 levels predicting PR had an area under the receiver operating curve of 0.68 and a model with both IFX14 level and CRP14 >1.0 mg/dL had an area under the receiver operating curve of 0.74. IFX14 cut points of >3, >4, and >7 µg/mL had positive predictive values of 64%, 76% and 100%, respectively, for predicting PR. Conclusions:Both IFX levels and CRP at week 14 were significantly associated with week 54 efficacy. A model combining both CRP and IFX at week 14 may help predict remission at week 54.

Fecal microbial transplant via nasogastric tube for active pediatric ulcerative colitis.

Background: Ulcerative colitis (UC), a chronic inflammatory disease of the large intestine, is characterized by a dysregulated immune reaction. UC is associated with fecal dysbiosis. Human and animal studies support the fact that the gastrointestinal microbiome may trigger the intestinal immune response, resulting in UC. Fecal microbial transplantation (FMT), by changing the gastrointestinal microbiome of patients with UC, may be a therapeutic option. Methods: Four patients with moderate symptoms defined by the Pediatric Ulcerative Colitis Activity Index were enrolled in a prospective, open-label study of FMT via nasogastric tube in pediatric UC (US Food and Drug Administration IND 14942). After the donor and patient evaluation, patients received FMT with follow-up evaluations at 2, 6, and 12 weeks after transplantation. Study subjects were maintained on their pretransplant medications. The Pediatric Ulcerative Colitis Activity Index score, C-reactive protein, and stool calprotectin were completed during each study visit. Results: Four patients with UC were enrolled (all boys). Ages ranged from 13 to 16 years. Patients tolerated FMT without adverse effects. None of the patients clinically improved with FMT, nor were there any significant changes in stool calprotectin or laboratory values, including C-reactive protein, albumin, and hematocrit. Three individuals received additional standard medical therapies before the end of the study. Conclusions: This study, although showing that single-dose FMT via nasogastric tube is well tolerated in active pediatric UC, did not show any clinical or laboratory benefit.

The politics of performance: methodological challenges of researching children’s experiences of childhood through the lens of participatory video

This paper examines the value of participatory video (PV) for exploring childhood and children’s experiences within the context of a larger research project which sought to examine the everyday lives of residents in a neighbourhood identified as ‘disadvantaged’. Participatory methods are often premised on ameliorating the gap between the concepts and models of researchers and those of individuals and communities. However, within PV, there has been much less focus on the process of participation and its implications for research outcomes. This paper addresses this gap in order to explore how the children, researchers and residents co‐produced a visual narrative about life in the neighbourhood, and in particular, how a methodological focus on PV as process makes visible its potential to offer valuable insights not only into children’s social connectivities, relationships and friendships but also into the theorising of children’s identities and childhoods.

Salivary glands harbor more diverse microbial communities than gut in Anopheles culicifacies

BackgroundIn recent years, it has been well documented that gut flora not only influence mosquito physiology, but also significantly alter vector competency. Although, salivary gland and gut constitute key partners of the digestive system, it is still believed that salivary glands may harbor less flora than gut (Parasit Vectors 6: 146, 2013).MethodsUsing a metagenomic approach, we have identified for the first time the diverse microbial community associated with these two physiologically different tissues of the digestive system in the mosquito Anopheles culicifacies.ResultsA total of 17 different phyla could be assigned to the whole metagenomic dataset, predominated by the phylum Proteobacteria, Firmicutes, Bacteriodetes, Tenericutes and Actinomycetes. Common bacteria included the members of Enhydrobacter, Agromonas, Serratia, Ralsonia, Lactobacillus, Pseudomonas, Streptococcus, Rubrobacter, Anaerococcus, Methylobacterium, Turicibacter, Elizabethkingia etc. in both the tissues representing ‘core microbiota’ of the mosquito digestive system. Salivary associated unique bacterial community included the members of Chloriflexi, Chlorobi, Cyanobacteria, Nitrospira, TM7, Armatimonadetes, Planctomycetes, Fibrobacteres etc.ConclusionWe find that the salivary gland microbial community structure is more diverse than gut of the mosquito, probably due to differential feeding associated engagements such as food acquisition, ingestion and digestion processes.

An unusual cause of respiratory distress: live leech in the larynx

A foreign body in the respiratory tract is an emergency and requires immediate attention, because the ensuing airway obstruction may cause hypoxia and death. We are reporting the successful management of a case in which a live leech was in the larynx, causing respiratory distress. The presence of a live foreign body should be included as a differential diagnosis of acute onset respiratory distress in areas where drinking pond and river water is common.