Fertility and reproductive outcomes following high-energy pelvic fractures: A systematic review and meta-analysis.

BACKGROUND: There is a need to decipher the effect of pelvic fractures (PFs) upon female fertility and live birth rate, as data including treatment regimens in large, unselected populations remain scarce. OBJECTIVES: To assess the effect of high energy PFs upon female fertility and live birth rate. SEARCH STRATEGY: Literature search for relevant studies was performed up to March 2022 in five databases: Embase, MEDLINE, CAB Abstracts, ClinicalTrials.gov, and Google Scholar. SELECTION CRITERIA: Retrospective studies assessing live birth, infertility, and dyspareunia rates following PFs. DATA COLLECTION AND ANALYSIS: Data were extracted from studies independently by two authors. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. MAIN RESULTS: A total of 763 female patients of median age 27.8 years (95% CI 22-38 years) were included with median follow up of 5 years. Among PF patients, infertility hazard ratio (HR) 1.18 (95% CI 0.76-1.84, P = 0.47; I2  = 18%) and dyspareunia HR 0.60 (95% CI 0.34-1.08, P = 0.09; I2  = 66%), did not significantly differ from the age-matched literature-reported rates among non-PF patients. CONCLUSIONS: No significant differences of live birth, infertility, and dyspareunia rates across patients with PFs were found compared with non-PF counterparts.

Integrative, In Silico and Comparative Analysis of Breast Cancer Secretome Highlights Invasive-Ductal-Carcinoma-Grade Progression Biomarkers.

Globally, BC is the most frequently diagnosed cancer in women. The aim of this study was to identify novel secreted biomarkers that may indicate progression to high-grade BC malignancies and therefore predict metastatic potential. A total of 33 studies of breast cancer and 78 of other malignancies were screened via a systematic review for eligibility, yielding 26 datasets, 8 breast cancer secretome datasets, and 18 of other cancers that were included in the comparative secretome analysis. Sequential bioinformatic analysis using online resources enabled the identification of enriched GO_terms, overlapping clusters, and pathway reconstruction. This study identified putative predictors of IDC grade progression and their association with breast cancer patient mortality outcomes, namely, HSPG2, ACTG1, and LAMA5 as biomarkers of in silico pathway prediction, offering a putative approach by which the abovementioned proteins may mediate their effects, enabling disease progression. This study also identified ITGB1, FBN1, and THBS1 as putative pan-cancer detection biomarkers. The present study highlights novel, putative secretome biomarkers that may provide insight into the tumor biology and could inform clinical decision making in the context of IDC management in a non-invasive manner.

Determinants of healthy ageing: a systematic review of contemporary literature.

BACKGROUND: Healthy ageing frameworks have been highly explored. Our objective was to assess existing frameworks for healthy ageing and to identify commonly described factors that can potentially act as determinants of healthy ageing. METHODS: We carried out a systematic review by searching five electronic databases (EMBASE, MEDLINE, Cochrane, PsychINFO, and CINAHL) from January 2010 to November 2020 to capture contemporary evidence. Eligible studies needed to report a clear framework of healthy ageing in humans, within one or more of three domains (physical, mental/cognitive, social), in English. No restriction was placed on geographical location. Retrospective studies, studies that did not report a framework of healthy ageing, and studies with a focus on diagnostic measures were excluded. RESULTS: Of 3329 identified records, nine studies met our eligibility criteria and were included. Most of the studies were qualitative or cross sectional, and a majority were carried out in Asia, followed by North America, Australia, and Africa. The ten determinants identified for healthy ageing include physical activity, diet, self-awareness, outlook/attitude, life-long learning, faith, social support, financial security, community engagement, and independence. CONCLUSIONS: We identified ten determinants of healthy ageing proposed by the contemporary evidence base. There appears to be increasing acknowledgement of the instrumental role of social and mental/cognitive well-being as determinants of healthy ageing. The extent to which each determinant contributes to healthy ageing requires further evaluation.

Benefits of music on theatre staff in a paediatric theatre setting: a staff survey.

BACKGROUND: Music has a long-standing place in the operating theatre. Nonetheless, limited studies have investigated the role of music during Ear Nose and Throat (ENT) surgical procedures. AIMS: To evaluate the benefits of background music on ENT theatre staff. METHODS: A 10-question survey was distributed to ENT theatre staff over a four week period. RESULTS: A total of 36 ENT theatre staff responded to the survey, a response rate of 86%. Most participants (61%) enjoyed the calming effect of background music in ENT surgery. The majority of participants responded that music did not affect their communication with other staff (69%), and improved their concentration (61%). Most respondents agreed that music can produce a sense of comfort for the patients (69%), and reduce anxiety before anaesthesia (75%). CONCLUSIONS: Background music can have a calming effect on staff in paediatric elective ENT surgery. This is a decision to be made by the surgical team with direct patient care and, if there is any concern about communication and distraction, then it is to be avoided.

Decoding infraorbital dark circles with lasers and fillers.

BACKGROUND: The degree and severity of dark circles varies according to the skin type, age, and lifestyle. OBJECTIVES: To evaluate different non-surgical treatment options for dark circles. METHODS: In a private practice setting in the UK and India, 34 patients with dark circles with different Fitzpatrick skin types were treated with fillers (Group 1), lasers (Group 2), and fillers and lasers combined (Group 3). Pre and post treatment photos were taken and subjective and objective outcomes in appearance were reported. RESULTS: All treatment options were effective in all three groups with minimal side effects reported. No statistically significant difference was found between the three treatment groups. Patients who had tear troughs and/or hollow eyes responded well to fillers, patients with loose and wrinkled skin to CO2 laser, patients with tear troughs and hyperpigmentation to fillers, Q switched Nd:YAG and topical agents and patients with tear troughs and veins to fillers and long pulsed Nd:YAG lasers. Most patients (82%) rated the improvement in their appearance as excellent. CONCLUSIONS: All 3 treatment modalities were effective in the reduction of periorbital dark circles depending on underlying cause. Non-surgical treatments are capable of correcting and improving dark circles with minimum complications and downtime.

Mindfulness training for borderline personality disorder: A systematic review of contemporary literature.

Mindfulness is a component of several psychotherapies. Nonetheless, its effectiveness in borderline personality disorder (BPD) management remains obscure. This systematic review examined the effect of mindfulness training in BPD patients. Cochrane Central Register of Controlled Trials, CAB Abstracts, Embase, MEDLINE and APA PsycInfo were searched until 30 June 2021. Five trials with 294 participants were included. Improvements were reported in participants' levels of impulsivity, in their emotion dysregulation patterns, in their attention skills and in their mindfulness-related capacities including decentering and nonjudging. The findings suggest that mindfulness training may be an effective tool for alleviating certain aspects of BPD symptomatology. More research is needed before definitive conclusions can be reached about the effectiveness of mindfulness training in the treatment of BPD patients, and this remains to be elucidated in larger structured clinical trials, with longer follow-ups.

Obstetric anal sphincter injury events prior and after Episcissors-60 implementation: A systematic review and meta-analysis.

OBJECTIVE: To assess the effect of Episcissors-60 upon obstetric anal sphincter injuries (OASIS) reduction in nulliparous women. STUDY DESIGN: Independent literature search for relevant studies was performed up to 30th May 2021 on five databases: Embase (OVID), MEDLINE (R) (OVID), CAB Abstracts (OVID), ClinicalTrials.gov, and Google Scholar. The primary outcome was to assess OASIS events prior and after Epi-60 implementation in clinical practice in natural births (NB), whilst secondary outcomes included overall operative vaginal delivery (OVD) %/spontaneous vaginal deliveries (SVD) % deliveries, episiotomy rates and operator satisfaction. All included studies (retrospective, prospective and time-series) examined the effect of Episcissors-60 implementation upon observed OASIS %. RESULTS: A total of 14,027 nulliparous females were included in the meta-analysis. Overall, study heterogeneity was high at I2: 79% with collectively fair quality of studies, as assessed by the Newcastle-Ottawa scale. Overall, this analysis highlights significant differences of OASIS events that might suggest their implementation as standard practice [RD -0.02, 95% CI -0.03 to 0.00; P = 0.03]. CONCLUSION: The present analysis highlights significant differences of OASIS events pre- and post- Epi-60, that may suggest Episcissors-60 implementation as standard practice. Nonetheless, to ensure data integrity, well reported observational studies and robust randomized controlled trials (RCTs) are required prior to introduction of Epi-60 as standard episiotomy technique in clinical practice.

Efficacy of ulipristal acetate in women with fibroid induced menorrhagia: A systematic review and meta-analysis.

AIM: To evaluate the efficacy of UPA in women with fibroid induced menorrhagia. METHODS: Embase, MEDLINE, CAB Abstracts, Cochrane Central Register of Controlled Trials, PsychInfo were searched up to 18th May 2020 and updated on 7th February 2021. Randomised controlled trials evaluating the efficacy of UPA in women with fibroid induced menorrhagia were included in the study. RESULTS: Two authors independently reviewed and extracted the study data. Statistical heterogeneity was quantified using I2 statistics. Publication bias and data asymmetry was assessed by funnel plots. A meta-analysis was conducted where appropriate. Six studies were eligible for inclusion. UPA (5 mg and 10 mg) achieved statistically significant amenorrhoeic outcome when compared to placebo (p<0.00001). Increased adverse events (AE) profile was observed in the higher UPA dose, however, did not reach statistical significance. CONCLUSIONS: This review demonstrates the efficacy of UPA in achieving amenorrhoea in women with fibroid induced menorrhagia. However, the favourable dose of UPA remains inconclusive when AE profile is taken into account. Evidence remains obscure regarding liver damage and further research is warranted to attain a conclusive outcome.

Clinical frailty scale as a point of care prognostic indicator of mortality in COVID-19: a systematic review and meta-analysis.

BACKGROUND: COVID-19 has resulted in the largest pandemic experienced since 1918, accounting for over 2 million deaths globally. Frail and older people are at the highest risk of mortality. The main objective of the present research was to quantify the impact of clinical frailty scale (CFS) by increasing severity of frailty and to identify other personal prognostic factors associated with increased mortality from COVID-19. METHODS: This study offers a contemporary systematic review and meta-analysis to analyse the stratified mortality risk by increasing CFS sub-categories (1-3, 4-5 and 6-9). Databases searched included EMBASE, MEDLINE, CAB Abstracts, PsychInfo, and Web of Science with end-search restriction the 18th December 2020. Publications identified via MedRevix were followed up on the 23rd March 2021 in peer-reviewed database search, and citations were updated as published. Prospective and retrospective cohort studies which reported the association between CFS and COVID-19 mortality were included. Thirty-four studies were eligible for systematic review and seventeen for meta-analysis, with 81-87% (I2) heterogeneity. FINDINGS: All studies [N: 34] included patients from a hospital setting, comprising a total of 18,042 patients with mean age 72.8 (Min: 56; Max: 86). The CFS 4-5 patient group had significantly increased mortality when compared to patients with CFS 1-3 [(RE) OR 1.95 (1.32 (95% CI), 2.87 (95% CI)); I2 81%; p = 0.0008]. Furthermore, CFS 6-9 patient group displayed an even more noticeable mortality increase when compared to patients with CFS 1-3 [(RE) OR 3.09 (2.03, 4.71); I2 87%; p<0.0001]. Generic inverse variance analysis of adjusted hazard ratio among included studies highlighted that CFS (p = 0.0001), male gender (p = 0.0009), National Early Warning Score (p = 0.0001), Ischaemic Heart Disease (IHD) (p = 0.07), Hypertension (HT) (p<0.0001), and Chronic Kidney Disease (CKD) (p = 0.0009) were associated with increased COVID-19 mortality. INTERPRETATION: Our findings suggest a differential stratification of CFS scores in the context of COVID-19 infection, in which CFS 1-3 patients may be considered at lower risk, CFS 4-5 at moderate risk, and CFS 6-9 at high risk of mortality regardless of age. Overall, our study not only aims to alert clinicians of the value of CFS scores, but also highlight the multiple dimensions to consider such as age, gender and co-morbidities, even among moderately frail patients in relation to COVID-19 mortality. FUNDING: None.

Uterine smooth muscle tumour of uncertain malignant potential and in vitro fertilization treatment in an infertile patient.

The term smooth uterine muscle of uncertain malignant potential (STUMP) indicates a group of uterine smooth muscle tumours that cannot be diagnosed unequivocally as malignant but does not fulfil the criteria for leiomyoma, or its variants. In this case, we present a woman treated for infertility who presented with an asymptomatic cervical mass, diagnosed as STUMP after three cycles of controlled ovarian stimulation. We reviewed the literature with particular emphasis on the effects of STUMP upon fertility, up-to-date guidance regarding the management of patients' wishing fertility-sparing approaches and obstetric outcomes. To the best of our knowledge, this is the first case report of STUMP in a patient that has undergone multiple in vitro fertilization treatments as well as the first to provide a putative biological basis for the efficacy of gonadotropin-releasing hormone agonists, in this patient group.

The known burden of Huntington disease in the North of Scotland: prevalence of manifest and identified pre-symptomatic gene expansion carriers in the molecular era.

BACKGROUND: Huntington disease prevalence was first estimated in Grampian, northern Scotland in 1984. Molecular testing has since increased ascertainment. OBJECTIVE: To estimate the prevalence of manifest Huntington disease and identified pre-symptomatic gene expansion carriers (IPGEC) in northern Scotland, and estimate the magnitude of biases in prevalence studies that rely upon routine coding in primary care records. METHODS: Cases were ascertained using North of Scotland genetic laboratory, clinic, and hospital records. Prevalence was calculated for manifest and IPGEC on 01/07/2016 and 01/01/2020 and compared with local published data. RESULTS: The prevalence of manifest Huntington disease in northern Scotland in 2020 was 14.6 (95% CI 14.3-15.3) per 100,000, and of IPGEC was 8.3 (95% CI 7.8-9.2) per 100,000. Whilst the population of northern Scotland decreased by 0.05% between 2016 and 2020, the number of manifest and identified pre-symptomatic gene expansion carriers increased by 7.4% and 23.3%, respectively. Manifest disease in Grampian increased by 45.9% between 1984 and 2020. More women than men had a diagnosis. General Practice coding underestimated symptomatic molecularly confirmed prevalence by 2.2 per 100,000 people. CONCLUSION: Even in an area with previously high ascertainment, there has been a 45.9% increase in manifest Huntington disease over the last 30 years. Within our catchment area, prevalence varies between health board regions with similar community-based services. Such variation in prevalence could have major drug cost and service delivery implications, especially if expensive, complexly administered therapies prove successful. Health services should gather accurate population-based data on a regional basis to inform service planning.

Delineation of an unknown significance FANCA genetic variant in a recurrent breast cancer patient.

Fanconi anaemia is a heterogeneous condition associated with mutations in the Fanconi anaemia complementation group (FANC). The FANC group has also been extensively associated with tumourigenesis due to its intricate association with the cellular repair mechanism. In this case report, we are drawing initial associations between a previously unreported FANC-A gene point mutation (P1222L) and familial breast cancer, by examining the presentation and management of a 65-year-old female patient with history of bilateral breast cancer of two different histological categories (ductal and in situ lobular). Here, we present a further genetic analysis beyond the common clinical practice to understand the patient's genetic predisposition and improve their long-term management.

Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum.

PURPOSE: PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. METHODS: Thirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy. RESULTS: Thirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of -7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently. CONCLUSION: This study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk-benefit evaluations for sirolimus treatment in PROS.