Dual-energy computed tomography for the differentiation of uric acid stones: ex vivo performance evaluation

We assessed the potential of dual-energy computed tomography (CT) for the differentiation between uric acid (UA)-containing and non-UA-containing urinary stones. Forty urinary stones of 16 different compositions in two sizes (< and >/= 5 mm) were examined in an ex vivo model. Thirty stones consisted of pure calcium oxalate (whewellite or wheddellite), calcium phosphate (apatite, brushite, or vaterite), ammonium magnesium phosphate (struvite), UA, ammonium acid urate, ammonium phosphate, sodium hydrogen urate, or cystine, and ten stones were of mixed composition (UA-sodium hydrogen urate, whewellite-urate, wheddellite-urate, whewellite-brushite, or whewellite-brushite-struvite). Scans were performed using dual-source CT in a dual-energy mode with the tubes simultaneously operating at 80 and 140 kV. Two readers analysed the data with respect to stone attenuation at each energy level. The stones were classified as UA- or non-UA-containing using manual attenuation measurements and software analysis results. Sensitivity, specificity, PPV, and NPV were calculated using crystallographic stone analysis as the gold standard. Twenty-six out of 40 stones (65%) contained no UA; 14 stones (35%) contained UA. When compared with UA-containing stones, the differences in attenuation values at 80 and 140 kV were significantly (P < 0.001) higher in stones containing no UA. The software automatically mapped 39/40 stones (98%). Only one (2%) 2 mm UA-stone was missed. The software correctly classified all detected stones as UA- or non-UA-containing. The attenuation values of the missed stone were manually plotted into the analysis sheet which allowed for the correct classification of the stone (containing UA). Therefore, the sensitivity, specificity, PPV, and NPV for the detection of UA-containing stones was 100%. Ex vivo experience indicates that differentiation between UA- and non-UA-containing stones can be accurately performed using dual-source dual-energy CT.     

Feasibility of nasal epithelial brushing for the study of airway epithelial functions in CF infants.

BACKGROUND: For a better understanding of the early stages of cystic fibrosis (CF), it is of major interest to study respiratory epithelial cells obtained as early as possible. Although bronchoalveolar lavage has been proposed for this purpose, nasal brushing, which is a much less invasive technique, has seldom been used in CF infants. The aim of the present study was to examine in a few infants the feasibility of a nasal brushing technique for studies of airway epithelial functions in very young CF infants. METHODS: In 5 CF (median age 12, range 1-18 months) and 10 control infants (median age 5, range 1-17 months), a nasal brushing was performed by means of a soft sterile cytology brush, after premedication with oral paracetamol (15 mg/kg body weight) and rectal midazolam (0.2 mg/kg body weight). Samples were used for microbiological, cytological and functional studies. RESULTS: The procedure was well tolerated. Number of cells collected was similar in CF and non-CF patients (CF: median 230x10(3), range 42x10(3)-900x10(3); non-CF: median 340x10(3), range 140x10(3)-900x10(3)). Median number of viable cells was 67% (range 31-84%). Freshly obtained samples were successfully used for studies of ciliary beating frequency and cAMP-dependent chloride efflux. In 7 out of 17 cell cultures, confluence was obtained (CF: 2 out of 7; non-CF: 5 out of 10). The feasibility of studying protein release and mRNA expression of IL-8, IL-6 and TNF-alpha, under basal conditions and after stimulation by Pseudomonas aeruginosa, was demonstrated. CONCLUSIONS: By means of a simple nasal brushing technique easily performed and well tolerated, it is feasible, in infants, to harvest respiratory cells in sufficient amounts to study the airway epithelium using a broad range of techniques including cell culture.     

A novel stop mutation in the EDNRB gene in a family with Hirschsprung’s disease associated with Multiple Sclerosis

Purpose

We identified a girl with Hirschsprung’s disease (HSCR) whose mother and grandmother had HSCR associated with multiple sclerosis (MS). The aim of this study was to outline mutations in HSCR-related genes and MS susceptibility alleles in these three individuals.

Methods

The phenotypes were reviewed based on medical records. The three subjects had rectosigmoid HSCR verified with histopathology. The mother and grandmother fulfilled the McDonald criteria for MS. DNA was isolated from EDTA-preserved blood according to standard procedures. Exome sequencing aiming mainly at analyzing HSCR associated genes as well as Sanger sequencing for confirmation was performed.

Results

All affected individuals carry a novel heterozygous nonsense mutation in the EDNRB gene (c.C397T,p.R133X,refNM_000115), changing an arginine at position 133 into a premature stop codon. None of the subjects were homozygous for the HLA risk alleles for MS.

Conclusion

We report a novel non-sense EDNRB gene mutation in a girl with HSCR and her mother and grandmother with HSCR and MS. We propose that this EDNRB gene mutation plays a role in the etiology of HSCR and also makes the subjects susceptible to MS.     

Interventions to improve or facilitate linkage to or retention in pre-ART (HIV) care and initiation of ART in low- and middle-income settings – a systematic review

Introduction

Several approaches have been taken to reduce pre-antiretroviral therapy (ART) losses between HIV testing and ART initiation in low- and middle-income countries, but a systematic assessment of the evidence has not yet been undertaken. The aim of this systematic review is to assess the potential for interventions to improve or facilitate linkage to or retention in pre-ART care and initiation of ART in low- and middle-income settings.

Methods

An electronic search was conducted on Medline, Embase, Global Health, Web of Science and conference databases to identify studies describing interventions aimed at improving linkage to or retention in pre-ART care or initiation of ART. Additional searches were conducted to identify on-going trials on this topic, and experts in the field were contacted. An assessment of the risk of bias was conducted. Interventions were categorized according to key domains in the existing literature.

Results

A total of 11,129 potentially relevant citations were identified, of which 24 were eligible for inclusion, with the majority (n=21) from sub-Saharan Africa. In addition, 15 on-going trials were identified. The most common interventions described under key domains included: health system interventions (i.e. integration in the setting of antenatal care); patient convenience and accessibility (i.e. point-of-care CD4 count (POC) testing with immediate results, home-based ART initiation); behaviour interventions and peer support (i.e. improved communication, patient referral and education) and incentives (i.e. food support). Several interventions showed favourable outcomes: integration of care and peer supporters increased enrolment into HIV care, medical incentives increased pre-ART retention, POC CD4 testing and food incentives increased completion of ART eligibility screening and ART initiation. Most studies focused on the general adult patient population or pregnant women. The majority of published studies were observational cohort studies, subject to an unclear risk of bias.

Conclusions

Findings suggest that streamlining services to minimize patient visits, providing adequate medical and peer support, and providing incentives may decrease attrition, but the quality of the current evidence base is low. Few studies have investigated combined interventions, or assessed the impact of interventions across the HIV cascade. Results from on-going trials investigating POC CD4 count testing, patient navigation, rapid ART initiation and mobile phone technology may fill the quality of evidence gap. Further high-quality studies on key population groups are required, with interventions informed by previously reported barriers to care.     

Negative pressure wound treatment with computer‐controlled irrigation/instillation decreases bacterial load in contaminated wounds and facilitates wound closure

Microbial wound contamination is known to be a hindrance to wound healing. Negative pressure wound therapy (NPWT) with or without irrigation is known to optimise conditions in problem wounds. The aim of this study was to investigate the influence of computer‐controlled wound irrigation with NPWT on the bacterial load in contaminated wounds. A total of 267 patients were treated with NPWT with automated instillation because of problematic wounds using an antiseptic instillation solution. In 111 patients, a minimum of 4 operative procedures were necessary, and swabs were taken at least at the first and at the fourth operation in a standardised procedure. The number of different bacteria and the amount of bacteria were analysed during the course. In a subgroup of 51 patients, swabs were taken at all 4 operative procedures and analysed separately. In an overall analysis, the number of different bacteria and the amount of bacteria significantly decreased independent of wound localisation and diagnosis. NPWT with automated instillation demonstrates a positive influence in the reduction of bacterial load in problem wounds. Thus, it may help to optimise wound conditions before definite wound closure.     

Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula-feeding only neonatal rat model of necrotizing enterocolitis

Introduction

The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC).

Material and methods

Newborn Sprague–Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression.

Results

The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p < 0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1.

Discussion

Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease.     

Absence of donor CD40 protects renal allograft epithelium and preserves renal function

Blocking the CD40‐CD154 pathway prevents allograft rejection and induces donor‐specific tolerance in various experimental models. However, the translation to clinical studies has been hampered by unexpected thromboembolic complications of CD154‐blocking antibodies. Thus, blocking CD40 instead is now considered as an alternative strategy. Here, we evaluated the role of donor CD40 in allospecific T‐cell responses in vitro and in an in vivo model for renal transplantation. Fully MHC‐mismatched allografts from CD40‐deficient donors displayed better renal function than wild type. These functional data correlated with a lower level of apoptosis in renal tubular epithelial cells and higher expression of PD‐L1, which is most probably because of a reduced Th17 response in recipients of a CD40‐deficient donor. This hypothesis was supported in vitro, where donor CD40 expression was important for the induction of direct allospecific T‐cell responses. Especially the induction of Th17 cells was critically dependent on donor CD40. IL‐17A in conjunction with interferon‐γ in turn rendered renal tubular epithelial cells to a more costimulatory state by upregulating CD40 and downregulating PD‐L1 expression. In conclusion, CD40 blockade not only reduces the allospecific T‐cell responses, but might also lead to protection of tubular epithelium from apoptosis and thereby preserve kidney allograft function.     

Glucose modulates food‐related salience coding of midbrain neurons in humans

Although early rat studies demonstrated that administration of glucose diminishes dopaminergic midbrain activity, evidence in humans has been lacking so far. In the present functional magnetic resonance imaging study, glucose was intravenously infused in healthy human male participants while seeing images depicting low‐caloric food (LC), high‐caloric food (HC), and non‐food (NF) during a food/NF discrimination task. Analysis of brain activation focused on the ventral tegmental area (VTA) as the origin of the mesolimbic system involved in salience coding. Under unmodulated fasting baseline conditions, VTA activation was greater during HC compared with LC food cues. Subsequent to infusion of glucose, this difference in VTA activation as a function of caloric load leveled off and even reversed. In a control group not receiving glucose, VTA activation during HC relative to LC cues remained stable throughout the course of the experiment. Similar treatment‐specific patterns of brain activation were observed for the hypothalamus. The present findings show for the first time in humans that glucose infusion modulates salience coding mediated by the VTA. Hum Brain Mapp 37:4376–4384, 2016. © 2016 Wiley Periodicals, Inc.     

Echocardiographic monitoring during induction of general anesthesia with a miniaturized esophageal probe

Standard transesophageal echocardiography (TEE) does not allow cardiac monitoring during the induction of anesthesia because standard probes would limit the oropharyngeal space and impair mask ventilation and tracheal intubation. We hypothesized that a prototype, miniaturized TEE probe could be safely introduced transnasally in awake patients and that mask ventilation and orotracheal intubation could be performed while continuously monitoring left ventricular (LV) function during the induction of anesthesia. Forty-five patients were studied prospectively. The transnasal TEE probe was introduced through one of the nares and advanced until a transverse plane image of the LV at the level of the papillary muscles was seen. Anesthesia was induced, and the patients were ventilated with a mask that had previously been threaded over the TEE probe via a central perforation. Probe insertion was successful in 12 patients under local anesthesia alone and in an additional 31 patients with a combination of local anesthesia and mild sedation. In two cases, probe placement was unsuccessful. Overall, hemodynamic variables did not change significantly during insertion. No case of significant mucosal bleeding was seen. In one patient, regurgitation of gastric contents occurred without affecting the perioperative outcome. The two-dimensional echocardiogram image quality of the LV during the induction of anesthesia was good or acceptable in 95% of patients. We conclude that transnasal TEE can effectively be used for cardiac monitoring during the induction of general anesthesia. IMPLICATIONS: This study demonstrates that it is feasible and generally safe to introduce a miniaturized transesophageal echocardiography probe transnasally in awake cardiac risk patients to monitor cardiac performance during the induction of general anesthesia.