Do we really know the outcomes of prolapse surgery?

The exact success rate from conventional as well as new surgical procedures for pelvic organ prolapse is unknown possibly due to the lack of standardisation of outcome measures. Usually objective measures, e.g. Pelvic Organ Prolapse Quantification (POPQ) assessment have been used as the primary outcome in most studies which show that procedures such as anterior repair have a poor outcome. However these outcomes correlate poorly with subjective assessment and re-operation rates are lower than the anatomical failure rate suggesting that conventional surgery might not have as poor an outcome as previously suggested. Nonetheless, new procedures have been introduced for which efficacy and safety data are required via well conducted randomised controlled trials.     

Screening standards in assisted reproduction technologies: the screening of semen donors--where do we draw the line?

The most recent British Andrology Society guidelines have certainlystirred up much debate about the exclusion of donors that areseropositive for cytomegalovirus (CMV). Arguments will inevitablygo back and forth regarding the statistical risk of donors passingon infection and the point at which that risk becomes unacceptable.As with many of these debates, a number of different opinionswill be offered but a consensus will be almost impossible. However,the case of CMV highlights difficulties common to the screeningof donors for many infectious and genetic disorders.     

Radiofrequency ablation without the use of fluoroscopy – in what kind of patients is it feasible?

Introduction

The aim of the study was to describe the experience in performing ablation without fluoroscopy.

Material and methods

From 575 ablation procedures with CARTO performed in the period 2003–2008, 108 (42 M; age 40 ±16 years) were done without fluoroscopy. One patient had ablation using the Localisa system. There was one man with thrombocytopenia and two pregnant women.

Results

Right ventricular (RV) outflow tract arrhythmias and other RV arrhythmias were noted in 38 patients (35%) and 17 patients (15%), respectively. There were 5 (4.6%) left ventricular (LV) outflow tract arrhythmias and 19 (17.5%) other LV tachycardias; right accessory pathways in 17 patients (20%), in the middle cardiac vein in 1, Mahaim fibres in 1, and 3 cases of permanent junctional reciprocating tachycardias. One patient with CRT had AV node ablation (Localisa). In 3 patients there were also other arrhythmias treated: slow AV nodal pathway, typical flutter isthmus and right atrial tachycardia. In 2004, 1/96 CARTO procedures was done without fluoroscopy, in 2006 2/97, in 2007 19 (2 in LV) of 93, in 2008 87 (22 in LV) of 204. The percentage of ablations without fluoroscopy in every hundred CARTO procedures was: 1%, 1%, 8%, 23%, 46%, 28% (mean 18%). There were no procedure-related complications.

Conclusions

It is feasible to perform ablations within both right and left sides of the heart without fluoroscopy. The number and type of non-fluoroscopic procedures depends on the operator''s experience. Pregnant patients, with malignant history or with hematologic diseases should be ablated without fluoroscopy in centres that specialise in these kinds of procedures.     

Facial measurements in clinical genetics: How important are the instruments we use?

Prompted by our finding that a popular compendium of clinical measurements often suggests a transparent ruler as a suitable substitute for anthropometric calipers (which were typically used by the original researchers to collect the normative data), we compared facial measurements taken with a ruler and calipers. Our objectives were to compare facial measurement data taken with these instruments by two classes of observer: expert and inexperienced. Ten facial measurements were repeated on four medically normal women by one expert and one inexperienced observer. Both observers' data showed that the caliper-derived means were usually the larger, but, whereas the expert observer's caliper-derived data typically were the least variable, the novice observer had smaller standard deviations and ranges for the ruler-derived data. Statistically significant differences were found between the ruler- and caliper-derived data from both observers on all four subjects, except for subnasale-pogonion and stomion-pogonion. For the novice observer only, endocanthion-endocanthion, left exocanthion-endocanthion, and alare-alare were also nonsignificant. The calibrations of the sliding caliper and ruler were compared to determine if differences between them could explain the statistical results, but were the same. We concluded that the differences between the caliper- and ruler-derived measurements resulted because the ruler often could not be placed directly on the landmarks, as could the arms of the calipers. We recommend that clinicians interested in taking facial measurements to assess their patients consult the original publications for information on the techniques and instruments used so that reliable comparisons with the normative data can be made. Am. J. Med. Genet. 77:384–390, 1998. © 1998 Wiley-Liss, Inc.     

Is there a future for ovulation induction in the current era of assisted reproduction?

The clinical use of medical induction of ovulation in normogonadotrophic anovulatory women (WHO II), including polycystic ovary syndrome, is increasingly questioned. However, we believe that this treatment modality still represents a highly effective means of fertility treatment in women with low pregnancy chances without intervention. A conventional treatment algorithm involving clomiphene citrate (CC) followed by FSH induction of ovulation may result in a 71% cumulative singleton live birth rate. In attempts to improve treatment outcome further and reduce complication rates, new compounds such as insulin-sensitizing agents or aromatase inhibitors are currently used increasingly. Approaches such as patient selection for different treatment modalities on the basis of initial screening characteristics and alternative protocols for FSH ovulation induction may also be proposed to render treatment algorithms more patient tailored and therefore improve overall outcomes. More research is needed in this area, rather than referring these patients to assisted reproduction prematurely. This may lead to a more individually tailored approach for ovulation induction in a given patient, resulting in a further improvement of the balance between chances for success versus complications.     

Advances in Liver Transplantation: where are we in the pursuit of transplantation tolerance?

Liver transplantation is the ultimate treatment option for end-stage liver disease. Breakthroughs in surgical practice and immunosuppression have seen considerable advancements in survival after transplantation. However, the intricate management of immunosuppressive regimens, balancing desired immunological quiescence while minimizing toxicity has proven challenging. Diminishing improvements in long-term morbidity and mortality have been inextricably linked with the protracted use of these medications. As such, there is now enormous interest to devise protocols that will allow us to minimize or completely withdraw immunosuppressants after transplantation. Immunosuppression withdrawal trials have proved the reality of tolerance following liver transplantation, however, without intervention will only occur after several years at the risk of potential cumulative immunosuppression-related morbidity. Focus has now been directed at accelerating this phenomenon through tolerance-inducing strategies. In this regard, efforts have seen the use of regulatory cell immunotherapy. Here we focus particularly on regulatory T cells, discussing preclinical data that propagated several clinical trials of adoptive cell therapy in liver transplantation. Furthermore, we describe efforts to further optimize the specificity and survival of regulatory cell therapy guided by concurrent immunomonitoring studies and the development of novel technologies including chimeric antigen receptors and co-administration of low-dose IL-2.     

What is the most relevant standard of success in assisted reproduction? Should BESST really be the primary endpoint for assisted reproduction?

A major problem in IVF procedures is a high rate of induced iatrogenic complications including multiple gestations. Until now, transfer of at least three embryos followed by the subsequent elective reduction of triplet or higher order gestations to twins, single embryo transfer (SET) with cryopreservation of the remaining embryos, as well as the application of SET in unstimulated cycles, serves to illustrate the diversity characterizing the worldwide effort of achievement of pregnancy that aims to avoid possible complications. The BESST (birth emphasizing a successful singleton at term) endpoint constitutes an interesting parameter imposing the safety of SET. However, the observed success rate (11.1%) requires elucidation of the specific pattern of endometrial behaviour around the implantation window as well as its involvement in the further support of gestation. Consequently, research has to focus primarily on the improvement of technical parameters to achieve an acceptable success rate during the IVF procedures as compared with spontaneous gestations.     

How robust is the evidence for viruses in the induction of type 1 diabetes?

Viruses associated with type 1 diabetes have eluded definition as causal, with the exception of rubella virus. False-negative results may have occurred due to the focus on subjects at symptomatic onset, who may be heterogeneous and differently affected by viruses. In addition, assays have not always been sufficiently sensitive to deal with transient infections, and pancreatic tissue is scarce. Longitudinal studies of at-risk subjects and more sensitive DNA techniques now reveal that at initiation of islet autoimmunity, enteroviruses have only a small role, but are more likely to be important at symptomatic onset. Rotaviruses remain associated with initiation of islet autoimmunity, and generate strong T cell responses in the young.     

Are we really what we eat? Nutrition and its role in the onset of rheumatoid arthritis

Accumulating research evidence suggests that individual dietary factors and dietary patterns might be implicated in the risk of development of rheumatoid arthritis (RA). This narrative review aims to present this evidence and provide nutritional recommendations for reducing RA risk in susceptible individuals. Overall, a ‘Western’ type diet rich in energy intake, total and saturated fat, an unbalanced ratio of n-3 to n-6 fatty acids, high in refined carbohydrates and sugar and low in fiber and antioxidants might increase the risk of RA both directly through increasing inflammation and indirectly through increasing insulin resistance and obesity, with the latter being a known risk factor for RA. On the contrary, consumption of long-chain omega-3 polyunsaturated fatty acids, derived from fish and fish oil, is associated with a reduced risk of RA probably due to their anti-inflammatory properties. The Mediterranean diet (MD), rich in plant-based foods such as wholegrains, legumes, fruit, vegetables, extra-virgin olive oil and low in red meat consumption, might have the potential to reduce the risk of RA. Based on current research evidence, it is suggested that adherence to the MD enhanced with an increased consumption of fatty fish, reduced consumption of sugar-sweetened drinks and maintenance of a normal body weight, contributes to reducing the risk of RA. Further research on RA susceptibility will allow for more specific dietary recommendations to be made.     

Is it time for a new classification of mast cells? What do we know about mast cell heterogeneity?

Mast cells (MCs) are derived from committed precursors that leave the hematopoietic tissue, migrate in the blood, and colonize peripheral tissues where they terminally differentiate under microenvironment stimuli. They are distributed in almost all vascularized tissues where they act both as immune effectors and housekeeping cells, contributing to tissue homeostasis. Historically, MCs were classified into 2 subtypes, according to tryptic enzymes expression. However, MCs display a striking heterogeneity that reflects a complex interplay between different microenvironmental signals delivered by various tissues, and a differentiation program that decides their identity. Moreover, tissue-specific MCs show a trained memory, which contributes to shape their function in a specific microenvironment. In this review, we summarize the current state of our understanding of MC heterogeneity that reflects their different tissue experiences. We describe the discovery of unique cell molecules that can be used to distinguish specific MC subsets in vivo, and discuss how the improved ability to recognize these subsets provided new insights into the biology of MCs. These recent advances will be helpful for the understanding of the specific role of individual MC subsets in the control of tissue homeostasis, and in the regulation of pathological conditions such as infection, autoimmunity, and cancer.     

How do members of the public expect to use variants of uncertain significance in their health care? A population-based survey

PurposeGenomic sequencing can generate complex results, including variants of uncertain significance (VUS). In general, VUS should not inform clinical decision-making. This study aimed to assess the public's expected management of VUS.MethodsAn online, hypothetical survey was conducted among members of the Canadian public preceded by an educational video. Participants were randomized to 1 of 2 arms, VUS or pathogenic variant in a colorectal cancer gene, and asked which types of health services they expected to use for this result. Expected health service use was compared between randomization arms, and associations between participants’ sociodemographic characteristics, attitudes, and medical history were explored.ResultsAmong 1003 respondents (completion rate 60%), more participants expected to use each type of health service for a pathogenic variant than for a VUS. However, a considerable proportion of participants expected to request monitoring (73.4%) and consult health care providers (60.9%) for a VUS. There was evidence to support associations between expectation to use health services for a VUS with family history of genetic disease, family history of cancer, education, and attitudes toward health care and technology.ConclusionMany participants expected to use health services for a VUS in a colorectal cancer predisposition gene, suggesting a potential disconnect between patients’ expectations for VUS management and guideline-recommended care.     

Why does ovarian surgery in PCOS help? Insight into the endocrine implications of ovarian surgery for ovulation induction in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex disorder with heterogeneity of clinical and endocrine features. Ovarian surgery for ovulation induction has been used in the management of clomiphene citrate-resistant anovulatory women with PCOS. Various types of ovarian surgery have been employed (wedge resection, electrocautery, laser vaporization, multiple ovarian biopsies and others) and all procedures result in an altered endocrine profile after surgery. The mechanism behind the reversal of endocrinological dysfunction in PCOS after ovarian surgery remains incompletely understood. This review scans the literature systematically to identify the endocrine changes after ovarian surgery in PCOS, in order to glean some knowledge of the mechanism involved. After ovarian surgery in PCOS, a rapid reduction in serum levels of all ovarian hormones is seen, in combination with increased serum levels of pituitary hormones. Folliculogenesis is then initiated and ovarian hormone production increases, synchronically with a reduction of pituitary hormones. Continuation of follicle growth in subsequent cycles after ovarian surgery occurs in an environment with less androgens and lower LH and FSH levels compared with pretreatment levels. The endocrine changes found after ovarian surgery in PCOS women seem to be governed by the ovaries themselves. Rapid reduced secretion of all ovarian hormones restores feedback to the hypothalamus and pituitary, resulting in appropriate gonadotrophin secretion. Initiation of follicular development seems to be induced by increasing FSH levels following a reduction of the follicle excess and (intra-ovarian) androgen levels. Additionally, anti-Müllerian hormone and gonadotrophin surge attenuating factor probably have a role in the endocrine changes.     

How do Alliaceae stabilize their chromosome ends in the absence of TTTAGGG sequences?

TheArabidopsis-type telomeric repeats (5-TTTAGGG-3) are highly conserved. In most families of different plant phyla they represent the basic sequence of telomeres that stabilize and protect the chromosome termini. The results presented here show that Alliaceae and some related liliaceous species have no tandemly repeated TTTAGGG sequences. Instead, their chromosomes reveal highly repetitive satellite and/or rDNA sequences at the very ends. These apparently substitute the original plant telomeric sequences in Alliaceae. Both sequence types are very active in homologous recombination and may contribute to the stabilization of chromosome termini via compensation of replication-mediated shortening.Accepted for publication by M. Schmid     

Why do we need to use a zero reference? Reference influences on the ERPs of audiovisual effects

Using ERPs in the audiovisual stimulus, the current study is the first to investigate the influence of the reference on experimental effects (between two conditions). Three references, the average reference (AR), the mean mastoid (MM), and a new infinity zero reference (IR), were comparatively investigated via ERPs, statistical parametric scalp mappings (SPSM), and LORETA. Specifically, for the N1 (170–190 ms), the SPSM results showed an anterior distribution for MM, a posterior distribution for IR, and both anterior and posterior distributions for AR. However, the circumstantial evidence provided by LORETA is consistent with SPSM of IR. These results indicated that the newly developed IR could provide increased accuracy; thus, we recommend IR for future ERP studies.