Proposal for the existence of a nasogastric reflex in humans, as a potential cause of upper gastrointestinal symptoms

The nose is a gateway of air from the environment to the body and with its rich innervation from the olfactory and trigeminal nerves plays a critical role as a sensor in both human beings and primitive animals. Irritation of the nasal or paranasal mucosa may initiate a severe bradycardia, apnea, and vasoconstriction and increase the pulmonary airflow resistance. However, the interaction between nasal mucosa and the upper gastrointestinal tract is more often than not neglected in the clinical literature. We propose that a nasogastric reflex might exist with its afferent and efferent loops being the trigeminal and vagus nerves, respectively. The central connection of these loops is located at the pontomedullary level. The sensory inputs from the nasal mucosa to the general somatic afferent component of the brainstem including the pontine and medullary trigeminal nucleuses may induce the neighboring nucleus of the solitary tract and dorsal motor nucleus of the vagus. This initiates, via the efferent fibers of the vagus nerve, the manifestations of the vagal stimulation. The presence of a nasogastric reflex may warrant considerations as diseases of nose and paranasal sinuses may be the cause upper gastrointestinal symptmatology.     

Genetic variation in tumour necrosis factor and lymphotoxin is not associated with endometriosis in an Australian sample

BACKGROUND: Tumour necrosis factor (TNF) is a pleiotropic cytokine with a wide range of immunoregulatory effects. Variation in the promoter region of TNF and the neighbouring lymphotoxin alpha (LTA) gene might be associated with endometriosis. METHODS: We examined the association between endometriosis and common single-nucleotide polymorphisms (SNPs) or haplotypes in the TNF/LTA region in an Australian sample by analysing 26 SNPs in 958 endometriosis cases and 959 unrelated controls. We selected functional SNPs in the coding and the promoter region of the TNF gene and HapMap tagging SNPs and typed them on a Sequenom MassARRAY platform. A key SNP (rs1800630) in the promoter region typed in previous studies did not give reliable results. Therefore, we also examined a statistically identical (r(2) = 1) SNP (siSNP) (rs2844482), identified using the web based program ssSNPer. RESULTS: Genotype completion rate was 99.5% for SNPs spanning a region of 15.5 kb across the TNF/LTA locus. There was no evidence for association between endometriosis and TNF/LTA SNPs or SNP haplotypes in our case-control study. CONCLUSIONS: Our data suggest both TNF and LTA genes are not major susceptibility genes for endometriosis.     

Steroid-sparing maintenance immunosuppression is safe and effective after simultaneous liver-kidney transplantation

Optimization of maintenance immunosuppression (mIS) regimens in the transplant recipient requires a balance between sufficient potency to prevent rejection and avoidance of excessive immunosuppression to prevent toxicities and complications. The optimal regimen after simultaneous liver-kidney (SLK) transplantation remains unclear, but small single-center reports have shown success with steroid-sparing regimens. We studied 4184 adult SLK recipients using the Scientific Registry of Transplant Recipients, from March 1, 2002, to February 28, 2017, on tacrolimus-based regimens at 1 year post-transplant. We determined the association between mIS regimen and mortality and graft failure using Cox proportional hazard models. The use of steroid-sparing regimens increased post-transplant, from 16.1% at discharge to 88.0% at 5 years. Using multi-level logistic regression modeling, we found center-level variation to be the major contributor to choice of mIS regimen (ICC 44.5%; 95% CI: 36.2%-53.0%). In multivariate analysis, use of a steroid-sparing regimen at 1 year was associated with a 21% decreased risk of mortality compared to steroid-containing regimens (aHR 0.79, P = .01) and 20% decreased risk of liver graft failure (aHR 0.80, P = .01), without differences in kidney graft loss risk (aHR 0.92, P = .6). Among SLK recipients, the use of a steroid-sparing regimen appears to be safe and effective without adverse effects on patient or graft survival.     

Outcomes associated with Interstim therapy for medically refractory fecal incontinence

Background

Fecal incontinence is a common, socially debilitating disorder. Initial management involves dietary manipulation with bulking agents or antidiarrheal medications and pelvic floor biofeedback. For patients failing these modalities, traditional surgical approaches are morbid and of variable efficacy. Sacral nerve neuromodulation (Interstim, sacral nerve stimulation) was approved in May 2011 for management of medically refractory fecal incontinence. This report summarizes our experience with this treatment modality.

Methods

A prospectively maintained database from a colorectal specialty practice was reviewed from December 2011 to June 2013. Patient demographics, incontinence etiology, and medical treatment regimens were reviewed. Outcomes for Interstim placement and surgical morbidity were reviewed.

Results

A total of 330 patients were evaluated in the clinic for fecal incontinence during the study period. A total of 33 patients (10%) were offered Interstim therapy. The mean age was 63 (39 to 91) years, and 91% (30 of 33) were female. The etiology of the incontinence was obstetric (81%), rectal prolapse (11%), neurogenic (5%), and iatrogenic (3%). The entire group failed either supplemental fiber or antidiarrheal medications and 73% (24 of 33) failed pelvic floor biofeedback. The mean number of bowel accidents/2-week bowel diary before implant was 19 (9 to 52). After phase I implant, 88% (29 of 33) experienced a successful test phase and proceeded to phase II permanent implant. The mean number of bowel accidents/2-week diary postimplant was 3 (0 to 12). A trend toward less severe episodes of incontinence postimplant was observed. There were no complications associated with either the phase I or phase II implant. There were no phase II failures although 1 patient underwent device explant 9 months after phase II implant for chronic pain.

Conclusions

Sacral nerve neuromodulation (Interstim, sacral nerve stimulation) is an effective and efficacious tool for management of medically refractory fecal incontinence that offers a less morbid surgical approach to this problem. Interstim should be considered the first-line surgical approach for medically refractory fecal incontinence.