Comparison of luteal support protocols in fresh IVF/ICSI cycles: a network meta-analysis.

Despite the proven superiority of various luteal phase support protocols (LPS) over placebo in view of improved pregnancy rates in fresh cycles of IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycles, there is ongoing controversy over specific LPS protocol selection, dosage, and duration. The aim of the present study was to identify the optimal LPS under six core aspects of ART success, clinical pregnancy, live birth as primary outcomes and biochemical pregnancy, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS) events as secondary outcomes. Twelve databases, namely Embase (OVID), MEDLINE (R) (OVID), GlobalHealth (Archive), GlobalHealth, Health and Psychosocial Instruments, Maternity & Infant Care Database (MIDIRS), APA PsycTests, ClinicalTrials.gov, HMIC Health Management Information Consortium, CENTRAL, Web of Science, Scopus and two prospective registers, MedRxiv, Research Square were searched from inception to Aug.1st, 2023, (PROSPERO Registration: CRD42022358986). Only Randomised Controlled Trials (RCTs) were included. Bayesian network meta-analysis (NMA) model was employed for outcome analysis, presenting fixed effects, odds ratios (ORs) with 95% credibility intervals (CrIs). Vaginal Progesterone (VP) was considered the reference LPS given its' clinical relevance. Seventy-six RCTs, comparing 22 interventions, and including 26,536 participants were included in the present NMA. Overall CiNeMa risk of bias was deemed moderate, and network inconsistency per outcome was deemed low (Multiple pregnancy χ2: 0.11, OHSS χ2: 0.26), moderate (Clinical Pregnancy: χ2: 7.02, Live birth χ2: 10.95, Biochemical pregnancy: χ2: 6.60, Miscarriage: χ2: 11.305). Combinatorial regimens, with subcutaneous GnRH-a (SCGnRH-a) on a vaginal progesterone base and oral oestrogen (OE) appeared to overall improve clinical pregnancy events; VP + OE + SCGnRH-a [OR 1.57 (95% CrI 1.11 to 2.22)], VP + SCGnRH-a [OR 1.28 (95% CrI 1.05 to 1.55)] as well as live pregnancy events, VP + OE + SCGnRH-a [OR 8.81 (95% CrI 2.35 to 39.1)], VP + SCGnRH-a [OR 1.76 (95% CrI 1.45 to 2.15)]. Equally, the progesterone free LPS, intramuscular human chorionic gonadotrophin, [OR 9.67 (95% CrI 2.34, 73.2)] was also found to increase live birth events, however was also associated with an increased probability of ovarian hyperstimulation, [OR 1.64 (95% CrI 0.75, 3.71)]. The combination of intramuscular and vaginal progesterone was associated with higher multiple pregnancy events, [OR 7.09 (95% CrI 2.49, 31.)]. Of all LPS protocols, VP + SC GnRH-a was found to significantly reduce miscarriage events, OR 0.54 (95% CrI 0.37 to 0.80). Subgroup analysis according to ovarian stimulation (OS) protocol revealed that the optimal LPS across both long and short OS, taking into account increase in live birth and reduction in miscarriage as well as OHSS events, was VP + SCGnRH-a, with an OR 2.89 [95% CrI 1.08, 2.96] and OR 2.84 [95% CrI 1.35, 6.26] respectively. Overall, NMA data suggest that combinatorial treatments, with the addition of SCGnRH-a on a VP base result in improved clinical pregnancy and live birth events in both GnRH-agonist and antagonist ovarian stimulation protocols.

Assisted reproduction and congenital malformations: A systematic review and meta-analysis.

Prior studies have explored the links between congenital anomalies and assisted reproduction techniques, among other factors. However, it remains unclear whether a particular technique harbors an inherent risk of major congenital anomalies, either cumulatively or in an organ-specific manner. A meta-analysis was conducted using relevant studies from inception to February 2023 using six databases and two appropriate registers. Sources of heterogeneity were explored using sub-group analysis, using study weight, risk of bias and geographical location of original studies. Neonates conceived through assisted reproduction appear to have a higher risk of major congenital anomalies compared to naturally conceived neonates, OR 0.67 [95% CI 0.59, 0.76], I2 = 97%, p < 0.00001, with neonates conceived through intracytoplasmic sperm injection (ICSI) at a 9% higher chance of being affected in comparison to neonates conceived through in vitro fertilization (IVF). The increase in cardiac, gastrointestinal (GI), and neurological congenital anomalies appears to be independent of the assisted reproduction technique, while urogenital and musculoskeletal (MSK) anomalies were found to be increased in ICSI compared with IVF, OR 0.83 [95% CI 0.69, 0.98]; p = 0.03, I2 = 0%, and OR 0.65 [95% CI 0.49, 0.85]; p = 0.002, I2 = 80%, respectively. Neonates conceived using assisted reproduction techniques appear to be at higher risk of major congenital anomalies, with a higher risk attributable to conception using ICSI. The increase in cardiac, neurological, and GI congenital anomalies does not appear to be technique-specific, while the opposite held true for urogenital and MSK anomalies.

The association of assisted reproductive technology with fetal malpresentation: a systematic review and meta-analysis.

BACKGROUND: Since its introduction, assisted reproductive technology (ART) has developed into a common clinical practice around the world; yet it still raises a lot of questions. Throughout time, many researchers have investigated its association with several obstetric incidences and its consequences on perinatal outcomes. The aim of the current meta-analysis was to estimate the correlation between ART procedures and malpresentation of the fetus in singleton pregnancies. METHODS: The study was conducted according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines and prospectively registered under the PROSPERO database (CRD42023458084). Five databases (Embase, MEDLINE®, APA PsycInfo, Global Health, Health Management Information Consortium (HMIC)) and two additional sources were searched from inception to 31 May 2023. Quality of the included studies was assessed using the ROBINS-1 scale, whilst quality of evidence by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Summative and subgroup data as well as heterogeneity were generated by the Cochrane platform RevMan Web. RESULTS: Overall, 11 studies were included in the study with a total of 3,360,134 deliveries. Results indicate a higher risk of malpresentation at delivery in fetuses conceived through ART than those conceived naturally (RR: 1.50, (95% confidence interval (CI):1.30, 1.73)). This risk decreased when adjustments for potential confounders were applied (RR = 1.12, 95% CI 1.02, 1.23). CONCLUSIONS: Based on observational studies, this meta-analysis indicated that singleton pregnancies conceived through ART are associated with higher risk of malpresentation than those conceived naturally, albeit the difference was lower when potential confounders were examined. Thus, future large studies are required to better understand possible reversible and irreversible factors of this relationship.

Postoperative complications and surgical outcomes of robotic versus conventional nipple-sparing mastectomy in breast cancer: meta-analysis.

BACKGROUND: Breast cancer is the most common cancer worldwide, with remarkable advances in early diagnosis, systemic treatments, and surgical techniques. Robotic nipple-sparing mastectomy has been trialled; however, the complication rates, surgical outcomes, and oncological safety of this approach remain obscure. METHODS: A systematic search of the literature was conducted from conception until September 2022. Studies examining complications and operative variables where robotic nipple-sparing mastectomy was compared with conventional nipple-sparing mastectomy were included. Primary study outcomes were complications (Clavien-Dindo grade III complications, skin or nipple necrosis, seroma, haematoma, infection, implant loss, and wound dehiscence) and oncological safety (recurrence and positive margins). The secondary outcomes included operative variables, length of stay, cost-effectiveness, learning curve, and aesthetic outcome. RESULTS: A total of seven studies of overall fair quality, involving 1674 patients, were included in the systematic review and meta-analysis. Grade 3 complications were reduced in robotic nipple-sparing mastectomy without statistical significance (OR 0.60 (95 per cent c.i. 0.35 to 1.05)). Nipple necrosis was significantly reduced in robotic nipple-sparing mastectomy (OR 0.54 (95 per cent c.i. 0.30 to 0.96); P = 0.03; I2 = 15 per cent). Operating time (mean difference +58.81 min (95 per cent c.i. +28.19 to +89.44 min); P = 0.0002) and length of stay (mean difference +1.23 days (95 per cent c.i. +0.64 to +1.81 days); P < 0.0001) were significantly increased in robotic nipple-sparing mastectomy, whereas the opposite was true for blood loss (mean difference -53.18 ml (95 per cent c.i. -71.78 to -34.58 ml); P < 0.0001). CONCLUSION: Whilst still in its infancy, robotic breast surgery may become a viable option in breast surgery. Nonetheless, the oncological safety of this approach requires robust assessment.

Robotic nipple-sparing mastectomy has been tried, but it is still not clear how often complications happen or how much better it is for cancer patients than conventional nipple-sparing mastectomy. The aim of this study was to compare robotic nipple-sparing mastectomy with conventional nipple-sparing mastectomy. A thorough search of all articles was performed from the start to September 2022. The studies that compared robotic nipple-sparing mastectomy with conventional nipple-sparing mastectomy in terms of problems and surgical factors were included. Complications and cancer outcomes (recurrence and positive margins) were the most important things that the study looked at. Surgical time, blood loss, length of hospital stay, cost-effectiveness, learning curve, and patient-reported outcome measures were some of the other things that were studied. This systematic review and meta-analysis looked at seven studies with fair quality and included 1674 patients. Even though there were fewer major problems with robotic nipple-sparing mastectomy, the difference was not significant. In robotic nipple-sparing mastectomy, there was less nipple necrosis, but the overall time it took to operate was much longer and the cost was higher. The average amount of bleeding was less in robotic nipple-sparing mastectomy. The robotic nipple-sparing mastectomy method had a better patient-reported outcome and a steep learning curve. Robotic nipple-sparing mastectomy is a safe method, with fewer problems than other methods. Future studies should look into if it is safe for cancer patients in the long run.

The Role of Social Media in Breast Cancer Care and Survivorship: A Narrative Review.

Background: Female breast cancer (BC) is the most diagnosed cancer and the leading cause of malignancy-related death worldwide. With the widespread utilisation of the Internet, social media has presented an invaluable yet underemployed tool in the context of BC medical information dissemination, support hub formation, and patient empowerment. Summary: In this narrative review, we explore the untapped potential of social media in this context, caveats, and future directions that may aid in formulating a new era of patient led, in addition to patient-centred care. Key Messages: Social media represents a powerful tool with significant potential to enable the seeking and sharing of BC-related information, and enhance patient education, communication, engagement, and empowerment. However, its use is associated with a number of limitations, including confidentiality and addiction issues, excessive and inaccurate information, and a possibility of jeopardising the patient-doctor relationship. Further research is needed to shed more light on this topic.

Outcomes of Different Quality of Life Assessment Modalities After Breast Cancer Therapy: A Network Meta-analysis.

Importance: Improvement in clinical understanding of the priorities of patients with breast cancer (BC) regarding postoperative aesthetic outcomes (AOs) is needed. Objective: To assess expert panel and computerized evaluation modalities against patient-reported outcome measures (PROMs), the gold standard of AO assessment, in patients after surgical management of BC. Data Sources: Embase, MEDLINE, PsycINFO, PubMed, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were interrogated from inception through August 5, 2022. Search terms included breast conserving AND aesthetic outcome AND breast cancer. Ten observational studies were eligible for inclusion, with the earliest date of database collection on December 15, 2022. Study Selection: Studies with at least 1 pairwise comparison (PROM vs expert panel or PROM vs computerized evaluation with Breast Cancer Conservation Treatment cosmetic results [BCCT.core] software) were considered eligible if they included patients who received BC treatment with curative intent. Studies reporting solely on risk reduction or benign surgical procedures were excluded to ensure transitivity. Data Extraction and Synthesis: Two independent reviewers extracted study data with an independent cross-check from a third reviewer. The quality of included observational studies was assessed using the Newcastle-Ottawa Scale, and the level of evidence quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Confidence in network meta-analysis results was analyzed with the Confidence in Network Meta-analysis semiautomated tool. Effect size was reported using random-effects odds ratios (ORs) and cumulative ratios of ORs with 95% credibility intervals (CrIs). Main Outcomes and Measures: The primary outcome of this network meta-analysis was modality (expert panel or computer software) discordance from PROMs. Four-point Likert responses across PROMs, expert panel assessment, and BCCT.core evaluation of AOs were assessed. Results: A total of 10 observational studies including 3083 patients (median [IQR] age, 59 [50-60] years; median [range] follow-up, 39.0 [22.5-80.5] months) with reported AOs were assessed and homogenized in 4 distinct Likert response groups (excellent, very good, satisfactory, and bad). Overall network incoherence was low (χ22 = 0.35; P = .83). Overall, panel and software modalities graded AO outcomes worse than PROMs. Specifically, for excellent vs all other responses, the panel to PROM ratio of ORs was 0.30 (95% CrI, 0.17-0.53; I2 = 86%) and the BCCT.core to PROM ratio of ORs was 0.28 (95% CrI, 0.13-0.59; I2 = 95%), while the BCCT.core to panel ratio of ORs was 0.93 (95% CrI, 0.46-1.88; I2 = 88%). Conclusions and Relevance: In this study, patients scored AOs higher than both expert panels and computer software. Standardization and supplementation of expert panel and software AO tools with racially, ethnically, and culturally inclusive PROMs is needed to improve clinical evaluation of the journey of patients with BC and to prioritize components of therapeutic outcomes.

Effectiveness of progesterone rescue in women presenting low circulating progesterone levels around the day of embryo transfer: a systematic review and meta-analysis.

IMPORTANCE: Over the last decade, frozen embryo transfer (FET) has been increasingly used in contemporary fertility units. Despite the rapid increase in FET, there is still insufficient evidence to recommend an optimized protocol for endometrial preparation especially in patients with lower progesterone (P4) levels. Previous studies have concluded that P4 levels <10 ng/mL are associated with poorer pregnancy outcomes than those reported with high levels of circulating P4. OBJECTIVE: To identify whether rescue P4 dosing in patients with low P4 can salvage adverse outcomes associated with low P4 levels, resulting in outcomes comparable to patients with adequate progesterone. DATA SOURCES: The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines and prospectively registered under the PROSPERO database (CRD42022357125). Six databases (Embase, MEDLINE, APA PsycInfo, Global Health, HMIC Health Management Information Consortium, and Google Scholar) and 2 additional sources were searched from inception to August 29, 2022. STUDY SELECTION AND SYNTHESIS: Prospective and retrospective cohort studies, reporting the association between rescue progesterone and one or more pregnancy outcomes, were included. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS), while the quality of evidence by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Summative and subgroup data as well as heterogeneity were generated by the Cochrane platform RevMan (V. 5.4). MAIN OUTCOME MEASURE(S): To compare ongoing pregnancy rate as primary outcome and clinical pregnancy rate, miscarriage rate, and live birth rate as secondary outcomes between patients with low (<10 ng/mL) receiving rescue progesterone vs. those with adequate levels of P4 (≥10 ng/mL). RESULT(S): Overall, 7 observational studies were included in the analysis, with a total of 5927 patients of median age 34 (interquartile range [IQR]: 31.55, 37.13). Overall, patient group comparison, namely those with low P4 that received a rescue dose and those with adequate P4 levels, did not yield significant differences for either the primary or secondary outcomes. For ongoing clinical pregnancy, patients with low P4 receiving the rescue dose vs. those with adequate P4 levels was odds ratio (OR) 0.98 (95% CI: 0.78, 1.24; P = .86, I2: 41%), whereas for miscarriage events, OR was 0.98 (95% CI: 0.81, 1.17; P = .80, I2: 0). Equally, for clinical pregnancy, OR was 0.91 (95% CI: 0.78, 1.06; P = .24; I2: 33%), and for live birth, OR was 0.92 (95% CI: 0.77, 1.09; P = .33; I2: 43%). Subgroup analysis on the basis or rescue administration route successfully explained summative heterogeneity. CONCLUSION(S): Rescue P4 dosing in patients with low P4 results in ongoing pregnancy rate, clinical pregnancy and live birth rates were comparable to those of patients with adequate P4 levels. However, robust randomized controlled trials assessing rescue treatment in women with low P4 are needed to confirm these findings. Rescue P4 in patients with low circulating P4 around embryo transfer day may result in reproductive outcomes comparable to those with adequate P4 levels. STUDY REGISTRATION: CRD42022357125 (PROSPERO).

Comprehending the impact of #Breastcancer, #Breastsurgery and related hashtags on Twitter: A content and social network cross-sectional analysis #Breastcancer#Breastsurgery.

BACKGROUND: Early detection along with improved locoregional and systemic therapies have decreased breast cancer mortality and allowed for the clinical implementation of breast conserving surgical options, in turn reducing the clinical and psychosocial impact of mastectomy. To what extend this has been successfully conveyed through social media for breast cancer awareness, has not been previously investigated. METHODS: This study presents a content and social network cross-sectional descriptive study of Twitter and Google trends data worldwide from platform launch (2006 and 2004 respectively) until May 15th, 2022, in agreement with the STROBE guidelines. Tweets associated with the hashtags #Breastcancer, #Breastsurgery, #Oncoplasticsurgery, #Mastectomy, #Breastreconstruction, #Breastconservingsurgery were licensed and downloaded through the Vincitas and Tweetbinder online platforms. Associated available demographics, namely username, biography, location, date and language of post, were extracted from the Twitter dataset while interest percentage, location and language of search were extracted from the Google trends dataset. RESULTS: A total of 390111 unique tweets were generated by 127284 unique users, with 2 users engaging with all six hashtags. Original tweets constituted on average 39.1% [Min 30.7% to max 47.2%] of the total. Hashtag frequency increased on Twitter for all six searches during October, the breast-cancer awareness month, but not on Google trends. Cancer survivors engaged much more often with the hashtag #Breastcancer and #Mastectomy, whereas #Breastsurgery, #Oncoplasticsurgery, #Breastconservingsurgery, #Breastreconstruction were mostly used by health professionals. CONCLUSION: In this large qualitative and quantitative dataset, geo-temporal oscillations on Twitter and Google trends for hashtags relevant with breast cancer provide preliminary insights on information flow and user engagement. Understanding the effective use of social media platforms may provide the niche for disseminating evidence and promoting education on the surgical options of patients with breast cancer.

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.

What Went Wrong with VEGF-A in Peripheral Arterial Disease? A Systematic Review and Biological Insights on Future Therapeutics.

BACKGROUND: Of the 200 million patients worldwide affected by peripheral arterial disease (PAD), 4% will inevitably require major limb amputation. Previous systematic reviews presented a conflicting body of evidence in terms of vascular endothelial growth factor (VEGF) family member effects upon PAD natural progression. Despite that, modulation of intrinsic angiogenesis mechanisms targeting the VEGF family members still confers an attractive therapeutic target. The aim of the present study was to evaluate current evidence of VEGF modulation in the context of PAD. METHODS: This is a systematic literature review conducted according to the PRISMA guidelines and registered under PROSPERO database [CRD42021285988]. Independent literature search was performed up to April 1, 2022, on six databases. A total of 22 eligible studies were identified [N: 3, interventional patient studies; N: 19, animal studies]. Animal studies were appraised by the SYRCLE risk of bias tool, while human participant studies were assessed by the Newcastle Ottawa scale. Overall, quality of evidence was deemed fair for both animal and human studies. Main study outcomes were percentage change of injured vessel lumen stenosis and neointimal area formation upon VEGF modulation (inhibition or activation) in comparison with control group. FINDINGS: Nineteen animal models and three human participant studies were included in the systematic review and assessed separately. Positive modulation of VEGF-A in animal models resulted in a median decrease of 65.58% [95% CI 45.2; 71.87] in lumen stenosis [14 studies]. Furthermore, positive modulation of VEGF-A was found to reduce neointimal area proliferation by a median decrease of 63.41% [95% CI 41.6; 79.59] [14 studies]. Median end of study duration was 28 days [range: 14-84 days]. Data were insufficient to assess these outcomes with respect to VEGF-B or VEGF-C modulation. The limited number of available human studies presented inadequate outcome assessment despite their overall fair NOS grading. INTERPRETATION: VEGF-A-positive modulation decreases lumen stenosis and neointimal hyperplasia in PAD simulation animal models. Previously identified variability among outcomes was found to strongly stem from the variability of experimental designs. Clinical applicability and safety profile of VEGF-A in the context of PAD remain to be defined by a robust and uniformly designed body of further animal model-based experiments.

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.

Biomarker Determinants of Early Anthracycline-Induced Left Ventricular Dysfunction in Breast Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Breast cancer is the leading cause of cancer-related mortality amongst women. One of the most common chemotherapeutic agents used to treat breast cancer, anthracyclines, are associated with anthracycline-induced cardiotoxicity (ACIC). The aim of this meta-analysis was to quantify the predictive performance of biomarkers for early ACIC presentation in the breast cancer population. METHODS: Five databases were searched from inception to 1 January, 2022. Studies reporting the association between worsening left ventricular ejection fraction and biomarker level change were included. Overall, study heterogeneity varied between I2 0 and 78%. The primary outcome was incident left ventricular dysfunction, defined as left ventricular ejection fraction < 50-55% or a 10%-point decrease, in patients with breast cancer with congruent ≥ doubling of biomarker serology levels (growth differentiation factor 15, Galectin-3, pro B-type natriuretic peptide, high-sensitivity cardiac troponin T, placental growth factor, myeloperoxidase, high-sensitivity C-reactive protein, Fms-Related Tyrosine Kinase 1), 3 months after anthracycline exposure, relative to pre-anthracycline exposure levels, expressed as random effects, hazard ratios. The STRING protein interaction database was explored for experimentally validated biomarker interactions. RESULTS: Of 1458 records screened, four observational studies involving 1167 patients, with a low risk of bias, were included in this systematic review and meta-analysis. Doubling of growth differentiation factor 15 and Galectin-3 levels was associated with an increased risk of early ACIC, hazard ratio 3.74 (95% confidence interval 2.68-5.24) and hazard ratio 4.25 (95% confidence interval 3.1-5.18), respectively. Biomarker interactome analysis identified two putative ACIC biomarkers, neuropilin-1 and complement factor H. CONCLUSIONS: This is the first meta-analysis quantifying the association of biomarkers and early ACIC presentation in the breast cancer population. This may be of clinical relevance in the timely identification of patients at high risk of ACIC, allowing for closer monitoring and chemotherapy adjustments.

A systematic review of the impact of post-operative oral fluid intake on ileus following elective colorectal surgery.

INTRODUCTION: Ileus (delayed return of bowel function after surgery) is one of the highest priority research questions in modern day colorectal practice. Current Enhanced Recovery After Surgery (ERAS) guidance either does not include a specific recommendation for volume of postoperative oral fluids/foodstuffs or suggests ad-lib fluids. It is unclear if the volume of intake affects ileus rates. This systematic review aimed to determine the optimal fluid volume for patients to consume day one after elective colorectal surgery. METHODS: The literature was searched across seven databases, September 23, 2020. Randomised controlled trials of adults undergoing elective colorectal surgery, comparing oral intake postoperatively were eligible for inclusion. Two blinded reviewers assessed papers with disagreements resolved by a third independent reviewer. Main outcomes were 'resolution of postoperative ileus' and 'length of hospital stay'. Secondary outcomes included vomiting, mortality and complications. RESULTS: Of 2175 screened papers, eight were eligible for inclusion. All studies gave a clear liquid diet postoperatively. The comparison groups followed a traditional nil-by-mouth approach. All studies showed a minor reduction in postoperative ileus and hospital stay in the intervention group, but we are unable to determine the optimal postoperative oral fluid volume. The low number and poor quality of studies was a significant limitation. None of the trials were conducted within an ERAS protocol: only 883 patients were included in total. CONCLUSIONS: From the current literature it is unclear how postoperative oral fluid volume intake affects gastrointestinal function and ileus in elective colorectal surgical patients. This remains an important area for further research.

Impact of diabetes on COVID-19 mortality and hospital outcomes from a global perspective: An umbrella systematic review and meta-analysis.

INTRODUCTION: To date, COVID-19 has claimed 4.9 million lives. Diabetes has been identified as an independent risk factor of serious outcomes in people with COVID-19 infection. Whether that holds true across world regions uniformly has not been previously assessed. METHODS: This study offers the first umbrella systematic review and meta-analysis to analyse the collective and geographically stratified mortality, ICU admission, ventilation requirement, illness severity and discharge rate amongst patients with diabetes. Five databases (EMBASE, MEDLINE, CAB Abstracts, PsychInfo and Web of Science) and 3 additional sources (SSRN's eLibrary, Research Square and MedRxiv) were searched from inception to 30 August 2021. Prospective and retrospective cohort studies, reporting the association between diabetes and one or more COVID-19 hospitalization outcomes, were included. This meta-analysis was registered on PROSPERO, CRD42021278579. Abbreviated MeSH terms used for search were as follows: (Diabetes) AND (2019 Novel Coronavirus Disease), adapted per database requirements. Exclusion criteria exclusion criteria were as follows: (1) none of the primary or secondary outcomes of meta-analysis reported, (2) no confirmed COVID-19 infection (laboratory or clinical) and (3) no unexposed population (solely patients with diabetes included). Quality of the included studies were assessed using the Newcastle-Ottawa Scale (NOS) whilst quality of evidence by the GRADE framework. Studies that were clinically homogeneous were pooled. Summative data and heterogeneity were generated by the Cochrane platform RevMan (V. 5.4). RESULTS: Overall, 158 observational studies were included, with a total of 270,212 of participants, median age 59 [53-65 IQR] of who 56.5% were male. A total of 22 studies originated from EU, 90 from Far East, 16 from Middle East and 30 from America. Data were synthesized with mixed heterogeneity across outcomes. Pooled results highlighted those patients with diabetes were at a higher risk of COVID-19-related mortality, OR 1.87 [95%CI 1.61, 2.17]. ICU admissions increased across all studies for patients with diabetes, OR 1.59 [95%CI 1.15, 2.18], a result that was mainly skewed by Far East-originating studies, OR 1.94 [95%CI 1.51, 2.49]. Ventilation requirements were also increased amongst patients with diabetes worldwide, OR 1.44 [95%CI 1.20, 1.73] as well as their presentation with severe or critical condition, OR 2.88 [95%CI 2.29, 3.63]. HbA1C levels under <70 mmol and metformin use constituted protective factors in view of COVID-19 mortality, whilst the inverse was true for concurrent insulin use. CONCLUSIONS: Whilst diabetes constitutes a poor prognosticator for various COVID-19 infection outcomes, variability across world regions is significant and may skew overall trends.

Road to conception and successful delivery for a facioscapulohumeral muscular dystrophy patient.

Facioscapulohumeral muscular dystrophy is a muscular dystrophy affecting all ages, primarily people in the second decade. The disease is initially presented with face, shoulder girdle, and upper arm involvement, followed by lower extremity muscle weakness. Disease progression is usually slow, although about one-fifth of patients will require a wheelchair to accommodate mobility. Women with this muscular dystrophy could rarely have poor birth outcomes, with facioscapulohumeral muscular dystrophy symptom deterioration post-partum. In this study, we present a case of a woman with a genetically confirmed facioscapulohumeral muscular dystrophy 1 who underwent cesarean section with epidural anesthesia with favorable outcomes following the procedure. Eight months post cesarean section, the patient reported no facioscapulohumeral muscular dystrophy symptom deterioration. We reviewed the literature with emphasis on large studies concerning facioscapulohumeral muscular dystrophy and birth outcomes and concluded that the hereby presented approach is important for the comprehensive obstetric care and future risk assessment and management in such patients.

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.

A systematic review of therapies for aortobronchial fistulae.

OBJECTIVE: The aim of the study was to summarize epidemiologic data about aortobronchial fistulae and compare outcomes (mortality, recurrence, reoperation) of open, staged, and endovascular repair of aortobronchial fistula. METHODS: A systematic literature review was conducted to identify eligible studies published between January 1999 and December 2019. The Cochrane Library, PubMed, and Scopus databases were used as search engines. Eligible studies included articles reporting postoperative outcomes (death/follow-up). Literature review revealed only case reports and small case series, and thus, only descriptive data with data heterogeneity were available. The corresponding authors were contacted to provide additional information or outcome updates (recurrence/reoperation/death). RESULTS: Overall, 214 patients (90 studies) underwent 271 procedures (including redo procedures and staged procedures). Most of the patients were treated by endovascular means (72.42%). Open surgical repair was performed in 21.96% and staged procedures in 5.6%. Aortobronchial fistulae were located most often in the descending thoracic aorta (zone 3 or 4) (64.6%) and in zone 2 (23.8%). Fourteen percent of aortobronchial fistulae developed after thoracic endovascular aneurysm repair. Recurrence or infection occurred in 20% (43) patients. Recurrences were, to some extent, associated with the presence of endoleak. Long-term antibiotic administration (>1 month) was instituted in 63 patients (29.4%), whereas 90 patients (42%) did not receive antibiotics beyond hospitalization. From the remaining 61 patients, 3 received lifelong antibiotics and for 58 patients data were not available. Considering outcomes, the mean follow-up was 25.1 months (0-188 months) and not significantly different among treatments. LIMITATIONS: Literature review has revealed only case reports and small case series, and thus, only descriptive data were available. Randomized controlled trials are not available due to the rarity of the disease, which significantly decreases the power of the present study. Also, this study reflects significant data heterogeneity due to the nature of the analyzed manuscripts and would benefit from large patient cohort studies that have not been conducted till today. CONCLUSIONS: Aortobronchial fistula is a complex disease. Endoleaks may be involved in the development and the recurrence process, and they should not be disregarded. Considering major outcomes (length of follow-up), the available treating strategies are equal, and thus, surgeons should feel confident to apply the treatment of their choice, keeping in mind their experience, patient's age, and clinical condition.