Robot-assisted surgery for the management of apical prolapse: a bi-centre prospective cohort study.

OBJECTIVE: Robot-assisted surgery is a recognised treatment for pelvic-organ prolapse. Many of the surgical subgroup outcomes for apical prolapse are reported together, leading to a paucity of homogenous data. DESIGN: Prospective observational cohort study (NCT01598467, clinicaltrials.gov) assessing outcomes for homogeneous subgroups of robot-assisted apical prolapse surgery. SETTING: Two European tertiary referral hospitals. POPULATION: Consecutive patients undergoing robot-assisted sacrocolpopexy (RASC) and supracervical hysterectomy with sacrocervicopexy (RSHS). METHODS: Anatomical cure (simplified Pelvic Organ Prolapse Quantification, sPOPQ, stage 1), subjective cure (symptoms of bulge), and quality of life (Pelvic Floor Impact Questionnaire, PFIQ-7). MAIN OUTCOME MEASURES: Primary outcome: anatomical and subjective cure. SECONDARY OUTCOMES: surgical safety and intraoperative variables. RESULTS: A total of 305 patients were included (RASC n = 188; RSHS n = 117). Twelve months follow-up was available for 144 (RASC 76.6%) and 109 (RSHS 93.2%) women. Anatomical success of the apical compartment occurred for 91% (RASC) and in 99% (RSHS) of the women. In all compartments, the success percentages were 67 and 65%, respectively. Most recurrences were in the anterior compartment [15.7% RASC (symptomatic 12.1%); 22.9% RSHS (symptomatic 4.8%)]. Symptoms of bulge improved from 97.4 to 17.4% (P < 0.0005). PFIQ-7 scores improved from 76.7 ± 62.3 to 13.5 ± 31.1 (P < 0.0005). The duration of surgery increased significantly for RSHS [183.1 ± 38.2 versus 145.3 ± 29.8 (P < 0.0005)]. Intraoperative complications and conversion rates were low (RASC, 5.3 and 4.3%; RSHS, 0.0 and 0.0%). Four severe postoperative complications occurred after RASC (2.1%) and one occurred after RSHS (1.6%). CONCLUSIONS: This is the largest reported prospective cohort study on robot-assisted apical prolapse surgery. Both procedures are safe, with durable results. TWEETABLE ABSTRACT: European bi-centre trial concludes that robot-assisted surgery is a viable approach to managing apical prolapse.

Chikungunya Virus Infection-associated Arthralgia in Adult Jamaicans Post-outbreak / Artralgia asociada con la infección del virus de Chikunguña en jamaicanos adultos con posterioridad al brote

ABSTRACT Objective: To report demographic and self-reported clinical characteristics associated with persistent and severe arthralgia 8-12 months post-chikungunya virus (CHIKV) infection. Methods: A cross-sectional study of 306 adults who self-reported CHIKV infection was conducted. Subjects were consecutively enrolled at public primary healthcare centres in urban and rural areas in Jamaica. Adults with arthralgic conditions were compared with those who reported no arthralgia. Binary logistic regression models were used to determine demographic and self-reported clinical factors associated with severe arthralgia and persistent arthralgia. Results: Most subjects (70.3%) reported arthralgia after CHIKV outbreak (age: 47.6 ± 18.5 years). Medical consultation (36.2%) and laboratory confirmation (1.4%) were low. The prevalence of persistent and severe arthralgia in the previous month was 30.3% and 27.5%, respectively. Severe arthralgia was associated with the female gender (odds ratio (OR): 2.44; 95% confidence level (CI): 1.08, 5.52) and pre-existing arthritis (OR: 3.78; 95% CI: 1.23, 11.62). Females showed a greater likelihood of persistent arthralgia (OR: 2.18; 95% CI: 1.09, 4.39). Conclusion: Self-perceived arthralgia was an important feature 8-12 months post-CHIKV infection and has implications for the recognition and management of arthritis/rheumatic conditions.

RESUMEN Objetivo: Reportar las características clínicas demográficas y auto-reportadas asociadas con una artralgia persistente y severa de 8-12 meses tras la infección del virus de chikunguña (CHIKV). Métodos: Se llevó a cabo un estudio transversal de 306 adultos que auto-reportaron su infección de CHIKV. Los sujetos fueron alistados consecutivamente en centros públicos de atención primaria en zonas urbanas y rurales de Jamaica. Los adultos con condiciones artrálgicas fueron comparados con adultos que no reportaron artralgia alguna. Los modelos de regresión logística binaria fueron utilizados para determinar los factores clínicos demográficos y auto-reportados que se asocian con artralgia severa y artralgia persistente. Resultados: La mayoría de los sujetos (70.3%) reportaron artralgia después del brote de CHIKV (edad: 47.6 ± 18.5 años). La consulta médica (36.2%) y la confirmación del laboratorio (1.4%) fueron bajas. La prevalencia de la artralgia persistente y la severa en el mes anterior fue de 30.3%y 27.5%, respectivamente. La artralgia severa estuvo asociada al género femenino (odds-ratio (OR): 2.44; intervalo de confianza (IC): 1.08, 5.52), y artritis preexistente (OR: 3.78; 95% (IC: 1.23, 11.62). Las hembras mostraron una mayor probabilidad de artralgia persistente (OR: 2.18; 95% IC: 1.09, 4.39). Conclusión: La artralgia auto-percibida fue una característica importante de la infección post-CHIKV de 8-12 meses, y tiene implicaciones para el reconocimiento y tratamiento de la artritis y las condiciones reumáticas.

A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis.

Cystic Fibrosis (CF) and its treatment result in an altered gut microbiota composition compared to non-CF controls. However, the impact of this on gut microbiota functionality has not been extensively characterised. Our aim was to conduct a proof-of-principle study to investigate if measurable changes in gut microbiota functionality occur in adult CF patients compared to controls. Metagenomic DNA was extracted from faecal samples from six CF patients and six non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq platform. Metabolomic analysis using gas chromatography-mass spectrometry was conducted on faecal water. The gut microbiota of the CF group was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430 meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared to the controls. Significant differences in metabolites occurred between the two groups. This proof-of-principle study demonstrates that measurable changes in gut microbiota functionality occur in CF patients compared to controls. Larger studies are thus needed to interrogate this further.

The altered gut microbiota in adults with cystic fibrosis.

BACKGROUND: Cystic Fibrosis (CF) is an autosomal recessive disease that affects the function of a number of organs, principally the lungs, but also the gastrointestinal tract. The manifestations of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the gastrointestinal tract, as well as frequent antibiotic exposure, undoubtedly disrupts the gut microbiota. To analyse the effects of CF and its management on the microbiome, we compared the gut microbiota of 43 individuals with CF during a period of stability, to that of 69 non-CF controls using 454-pyrosequencing of the 16S rRNA gene. The impact of clinical parameters, including antibiotic therapy, on the results was also assessed. RESULTS: The CF-associated microbiome had reduced microbial diversity, an increase in Firmicutes and a reduction in Bacteroidetes compared to the non-CF controls. While the greatest number of differences in taxonomic abundances of the intestinal microbiota was observed between individuals with CF and the healthy controls, gut microbiota differences were also reported between people with CF when grouped by clinical parameters including % predicted FEV1 (measure of lung dysfunction) and the number of intravenous (IV) antibiotic courses in the previous 12 months. Notably, CF individuals presenting with severe lung dysfunction (% predicted FEV1 ≤ 40%) had significantly (p < 0.05) reduced gut microbiota diversity relative to those presenting with mild or moderate dysfunction. A significant negative correlation (-0.383, Simpson's Diversity Index) was also observed between the number of IV antibiotic courses and gut microbiota diversity. CONCLUSIONS: This is one of the largest single-centre studies on gut microbiota in stable adults with CF and demonstrates the significantly altered gut microbiota, including reduced microbial diversity seen in CF patients compared to healthy controls. The data show the impact that CF and it's management have on gut microbiota, presenting the opportunity to develop CF specific probiotics to minimise microbiota alterations.

Da Vinci robot emergency undocking protocol.

The role of robot-assisted surgery across gynaecology is evolving with increasing numbers of procedures being undertaken with varying degrees of complexity. While the risk of conversion is low at approximately 1 %, the reasons for conversion are variable. These range from technical issues with the robot, surgical complications such as haemorrhage and anaesthetics issues such as an inability to ventilate the patient adequately. While many conversions to open or laparoscopic approach are not due to life-threatening indications, it is important that the theatre staff are aware of the indication and can perform an emergency undocking as effectively, efficiently and safely as possible when the need arises. Unfortunately, there is a paucity of the literature available outlining such protocols. For this reason, we developed an emergency undocking protocol clearly outlining the role of each theatre staff member and the need for clear concise communication.

Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model.

The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~10(9)microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~10(9) L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P<0.05), but did not alter other metabolic markers in healthy rats. Diabetes induced by STZ injection decreased body weight (P<0.05), increased intestinal length (P<0.05) and stimulated water and food intake. Insulin was decreased (P<0.05), whereas glucose was increased (P<0.001) in all diabetic groups, compared with non-diabetic controls. A decrease (P<0.01) in glucose levels was observed in diabetic rats receiving L. brevis DPC 6108, compared with diabetic-controls. Both the composition and diversity of the intestinal microbiota were affected by diabetes. Microbial diversity in diabetic rats supplemented with low GABA was not reduced (P>0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.

The Effect of Bariatric Surgery on Urinary Incontinence in Women.

BACKGROUND: Little is known regarding the effect of bariatric surgery on urinary incontinence. METHODS: Between September 2008 and November 2014, 240 female patients underwent bariatric surgery. RESULTS: The prevalence of urinary incontinence preoperatively was 45 % (108). Eighty-two (76 %) completed urinary function questionnaires pre-operatively and post-operatively. Fifty-seven (70 %) underwent laparoscopic gastric bypass, twenty-four (29 %) underwent sleeve gastrectomy and one underwent a banding procedure. Thirty-one (38 %) reported leaking on sneezing or coughing-stress urinary incontinence (SUI). Thirteen (16 %) complained of leaking before reaching the toilet-overactive bladder syndrome (OAB). The remaining thirty-eight (46 %) reported mixed symptoms. The mean pre-operative weight and BMI were 133 (18) kg and 50 (SD = 6.2) kg/m(2) respectively. The mean post-operative BMI drop was 16 (SD = 5.2) kg/m(2). Preoperatively, 61 (75 %) reported moderate to very severe urinary incontinence compared to 30 (37 %) post-operatively (χ (2) = 3.24.67, p = 0.050). Twenty-seven (33 %) patients reported complete resolution of their urinary incontinence. Fifty-one (62 %) patients required incontinence pads on a daily basis pre-operatively, compared to 35 (43 %) post-operatively (χ (2) = 22.211.6, p = 0.00). The mean International Consultation on Incontinence Questionnaire- Urinary Incontinence short form (ICIQ-UI SF) score was 9.3 (SD = 4.4) pre-operatively compared to 4.9 (SD = 5.3) post-operatively (t = 7.2, p = 0.000). The improvement score post-operatively was 8 (SD = 3). A significant difference in the ICIQ-UI SF was identified between OAB and SUI groups when adjusting for age, number of children, type of delivery and pre-op BMI (t = 1.98, p = 0.05). CONCLUSION: Bariatric surgery results in a clinically significant improvement in urinary incontinence. However, this is not proportional to pre-operative BMI, weight loss, age, parity and mode of delivery.

Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers.

OBJECTIVES: The relevance of spatial composition in the microbial changes associated with UC is unclear. We coupled luminal brush samples, mucosal biopsies and laser capture microdissection with deep sequencing of the gut microbiota to develop an integrated spatial assessment of the microbial community in controls and UC. DESIGN: A total of 98 samples were sequenced to a mean depth of 31,642 reads from nine individuals, four control volunteers undergoing routine colonoscopy and five patients undergoing surgical colectomy for medically-refractory UC. Samples were retrieved at four colorectal locations, incorporating the luminal microbiota, mucus gel layer and whole mucosal biopsies. RESULTS: Interpersonal variability accounted for approximately half of the total variance. Surprisingly, within individuals, asymmetric Eigenvector map analysis demonstrated differentiation between the luminal and mucus gel microbiota, in both controls and UC, with no differentiation between colorectal regions. At a taxonomic level, differentiation was evident between both cohorts, as well as between the luminal and mucosal compartments, with a small group of taxa uniquely discriminating the luminal and mucosal microbiota in colitis. There was no correlation between regional inflammation and a breakdown in this spatial differentiation or bacterial diversity. CONCLUSIONS: Our study demonstrates a conserved spatial structure to the colonic microbiota, differentiating the luminal and mucosal communities, within the context of marked interpersonal variability. While elements of this structure overlap between UC and control volunteers, there are differences between the two groups, both in terms of the overall taxonomic composition and how spatial structure is ascribable to distinct taxa.

Lightweight meshes: evaluation of mesh tissue integration and host tissue response.

INTRODUCTION: Differences in mesh composition may affect outcomes such as erosion, tissue integration and inflammation. The majority of commercially available meshes are type 1, manufactured from monofilament polypropylene with differing pore sizes and mechanical properties. OBJECTIVE: To assess the local tolerance of four commercially available meshes in terms of mesh integration and host tissue response. METHOD: Using an animal model, mesh was implanted onto the abdominal sheath. Animals were sacrificed at 7, 30 and 90 days and data collected. RESULTS: Strength of mesh-skin integration increased in all groups across the three time points. Polyform displayed highest strength of separation overall. VM PFR and Iprolite reached their maximum integration earliest. In regard to mesh abdominal wall integration Polyform had the greatest strength of separation, with Ultrapro displaying some weakening of integration at 30 and 90 days. Host tissue response was similar in all groups at each time point. CONCLUSION: Polyform and VM PFR have enhanced tissue integration when compared to Ultrapro. This decreased integration in Ultrapro may lead to increased mesh failure. The composition of mesh affects its integration and potentially its failure rate but not host tissue response. These observations in mesh characteristics may benefit the design of next generation meshes with a view to reducing failure rates and erosion.

Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat.

The atypical antipsychotic olanzapine is often associated with serious metabolic side effects including weight gain and increased visceral fat. These adverse events are a considerable clinical problem and the mechanisms underlying them are multifactorial and poorly understood. Growing evidence suggests that the gut microbiota has a key role in energy regulation and disease states such as obesity. Moreover, we recently showed that chronic olanzapine altered the composition of the gut microbiome in the rat. It is thus possible that treatments that alter gut microbiota composition could ameliorate olanzapine-induced weight gain and associated metabolic syndrome. To this end, we investigated the impact of antibiotic-induced alteration of the gut microbiota on the metabolic effects associated with chronic olanzapine treatment in female rats. Animals received vehicle or olanzapine (2 mg kg(-1) per day) for 21 days, intraperitoneal injection, two times daily. Animals were also coadministered vehicle or an antibiotic cocktail consisting of neomycin (250 mg kg(-1) per day), metronidazole (50 mg kg(-1) per day) and polymyxin B (9 mg kg(-1) per day) by oral gavage, daily, beginning 5 days before olanzapine treatment. The antibiotic cocktail drastically altered the microbiota of olanzapine-treated rats, and olanzapine alone was also associated with an altered microbiota. Coadministration of the antibiotic cocktail in olanzapine-treated rats attenuated: body weight gain, uterine fat deposition, macrophage infiltration of adipose tissue, plasma free fatty acid levels, all of which were increased by olanzapine alone. These results suggest that the gut microbiome has a role in the cycle of metabolic dysfunction associated with olanzapine, and could represent a novel therapeutic target for preventing antipsychotic-induced metabolic disease.

Robot-assisted surgery:--impact on gynaecological and pelvic floor reconstructive surgery.

The da Vinci Surgical System dominates robotic surgery, as the only robotic device to have FDA approval in gynaecology. The benefits of robot-assisted surgery include decreased length of stay, decreased blood loss and analgesic requirements. Ergonomic improvements allow the surgeon to operate with less risk of neck and back injury. Unfortunately the initial economic impact of purchasing and maintaining a robot are great but must be balanced with the potential savings from reduced length of stay and earlier return to normal activity. This review looks at the uses for the robot in both gynaecology and urogynaecology, assessing the efficacy of this modality compared to both straight stick (laparoscopy) and open procedures. We assess the benefits to both patient and surgeon from the available literature. Within the current economic environment we appraise the costs associated with the robot.

Characterisation of single nucleotide polymorphisms identified in the bovine lactoferrin gene sequences across a range of dairy cow breeds.

The lactoferrin gene sequences of 70 unrelated dairy cows representing six different dairy breeds were investigated for single nucleotide polymorphisms to establish a baseline of polymorphisms that exist within the Irish bovine population. Twenty-nine polymorphisms were identified within a 2.2kb regulatory region. Nineteen novel polymorphisms were identified and some of these were found within transcription factor binding sites, including GATA-1 and SPI transcription factor sites. Forty-seven polymorphisms were identified within exon sequences with unique polymorphisms that were associated with amino acid substitutions. These included a T/A SNP, identified in a Holstein Friesian animal, which resulted in a valine to aspartic acid substitution (Val89Asp) in the mature lactoferrin protein. Other SNPs of interest were associated with amino acid substitutions in the lactoferricin B peptide sequence and an A/G SNP, identified in a Jersey animal, was associated with a tyrosine to cysteine change (Tyr181Cys). The polymorphisms identified in the promoter region may have implications relating to lactoferrin expression levels in cows and those identified in the coding sequence indicate the existence of protein variants in the Irish bovine population. The data presented in this study emphasises the potential for lactoferrin to serve as a candidate gene to select for mastitis resistance with the aim of improving animal health.

Casein fermentate of Lactobacillus animalis DPC6134 contains a range of novel propeptide angiotensin-converting enzyme inhibitors.

This work evaluated the angiotensin-converting-enzyme (ACE)-inhibitory activities of a bovine sodium caseinate fermentate generated using the proteolytic capabilities of the porcine small intestinal isolate Lactobacillus animalis DPC6134 (NCIMB deposit 41355). The crude 10-kDa L. animalis DPC6134 fermentate exhibited ACE-inhibitory activity of 85.51% (+/-15%) and had a 50% inhibitory concentration (IC50) of 0.8 mg protein/ml compared to captopril, which had an IC50 value of 0.005 mg/ml. Fractionation of the crude L. animalis DPC6134 fermentate by membrane filtration and reversed-phase high-performance liquid chromatography (HPLC) generated three bioactive fractions from a total of 72 fractions. Fractions 10, 19, and 43 displayed ACE-inhibitory activity percentages of 67.53 (+/-15), 83.71 (+/-19), and 42.36 (+/-11), respectively, where ACE inhibition was determined with 80 microl of the fractions with protein concentrations of 0.5 mg/ml. HPLC and mass spectrometry analysis identified 25 distinct peptide sequences derived from alpha-, beta-, and kappa-caseins. In silico predictions, based on the C-terminal tetrapeptide sequences, suggested that peptide NIPPLTQTPVVVPPFIQ, corresponding to beta-casein f(73-89); peptide IGSENSEKTTMP, corresponding to alpha(s1)-casein f(201212); peptide SQSKVLPVPQ, corresponding to beta-casein f(166-175); peptide MPFPKYPVEP, corresponding to beta-casein f(124133); and peptide EPVLGPVRGPFP, corresponding to beta-casein f(210-221), contained ACE-inhibitory activities. These peptides were chosen for chemical synthesis to confirm the ACE-inhibitory activity of the fractions. Chemically synthesized peptides displayed IC50 values in the range of 92 microM to 790 microM. Additionally, a simulated gastrointestinal digestion confirmed that the ACE-inhibitory 10-kDa L. animalis DPC6134 fermentation was resistant to a cocktail of digestive enzymes found in the gastrointestinal tract.

The Snodgrass repair: is stenting always necessary?

To evaluate the need for stenting in Snodgrass hypospadias repairs. Sixty-five boys underwent hypospadias repairs between April 1996 and July 2001. A variety of techniques were employed. Snodgrass repair was performed in 39 patients, MAGPI in 18, Glanular approximation procedures in 4, Mathieu procedures in 3 and one Duckett Onlay-flap. Seventeen patients, all Snodgrass repairs, had placement of a urethral stent for one week postoperatively. Follow-up at six weeks and one year or when toilet-trained was carried out on all patients. A Fisher's exact test was performed analysing the difference in outcome of the distal Snodgrass repairs depending on the presence or absence of a urethral stent. The patient age at the time of surgery ranged from 8-115 months, with a median of 21 months. Postoperative complications included 1 stent migration, 1 urethral diverticulum and 4 fistulas. Also in one patient part of the ventral skin flap on one side sloughed away, this was debrided and allowed to close by secondary intention. The fistula rate in the entire group is 6%, with an incidence of 10.5% in patients undergoing Snodgrass repair. In the cases having Snodgrass repair for meatal position other than mid- or proximal shaft there was no statistical difference in the incidence of fistula whether or not a stent was used. The long-term follow-up of the entire group indicates that 5 patients developed meatal narrowing, 3 in stented Snodgrass repairs, one patient who had a MAGPI and one GAP patient. Otherwise the long-term outcome of the surgery has been excellent for the entire group. We believe that stenting can be abandoned in distal repairs without compromising patient outcomes.

Encrusted cystitis--an unusual cause of recurrent frank haematuria.

BACKGROUND: Encrusted cystitis associated with malakoplakia is described in the literature as a rare condition characterized by the formation of calcified plaques adherent to or embedded in the bladder mucosa. AIMS: We present the case of a 51-year-old male, presenting with recurrent haematuria associated with minimal exercise. Despite normal ultrasound, IVP, two calcified lesions on his bladder were found on cystoscopy. Conservative management was ineffective thereby necessitating a curative partial cystectomy. CONCLUSION: We would like to illustrate/discuss this rare but problematic condition with gross and microscopic pictures.