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Endometrial cell-derived conditioned medium in combination with platelet-rich plasma promotes the development of mouse ovarian follicles

Summary
Fertility preservation is one of the most important issues in assisted reproductive technology. Previous studies have shown that cytokines and growth factors can improve follicle growth. The endometrial stromal cells secrete various factors that are involved in maintaining the integrity of uterine and epithelial secretory function. The platelet-rich plasma contains a large assembly of platelets suspended in plasma that successfully improves the viability and growth of various cell lines. This work aimed to investigate the influences of conditioned medium (CM) and platelet-rich plasma (PRP) on the development of ovarian follicles in infertile mice due to cyclophosphamide (CYC) exposure. In this study, 65 healthy BALB/c female mice (∼28–30 g and 6-8 weeks old) in five groups were studied. Immunohistochemistry (IHC) was used to detect growth differentiation factor 9 (GDF9)-positive cells. The mRNA expression levels of SMAD1, SMAD2, and BMP15 was assessed using reverse transcription-polymerase chain reaction (RT-PCR) method. The expression levels of SMAD1, GDF9, BMP15, and SMAD2 in the CM+PRP group was significantly more than in the CM and PRP groups. In addition, live birth occurred in the CM+PRP group. Treatment with CM+PRP in infertile mice due to Cy exposure increased fertility and live-birth rate. In general, our study suggested that the CM and PRP combination could improve the growth of mice ovarian follicles in vivo.
 
 
Investigation of Breast Cancer Risk Factors in the Imam Hossein and Shohada-E Tajrish Hospitals of Tehran in 2019–2022: A case–control study
 
Abstract
Breast cancer is one of the most common cancers and causes of death worldwide. Various factors such as family history, lifestyle, the reproductive and social factors can influence the risk of breast cancer. In this study, we investigated breast cancer risk factors in Iranian women. The aim of this study was to investigate different risk factors for breast cancer. In this case–control study conducted in two hospitals in Tehran, 250 women with breast cancer were compared with 250 women without breast cancer as a control group. Data collection was done through checklists with questions about lifestyle, reproductive and social factors. Logistic regression was used. The level of statistical significance was set at P < 0.05 for all the tests. Our results showed stress and mental pressure [OR:1.77 (95% CI:1.51–2.09) (P < 0.001)], HRT [OR: 15.07 (95% CI: 2.46–289.68) (P < 0.001)], increasing age [OR:1.09 (95% CI:1.07–1.11) (P < 0.001)], increasing gravida [OR:2.68 (95% CI: 2.09–3.48) (P < 0.001)], increasing live birth number [OR:1.04 (95% CI:2.19–3.74) (P < 0.001)], being married [OR: 8.58 (95% CI: 4.36–18.92) (P < 0.001)], menopause [OR:2.95 (95% CI: 1.97–4.47) (P < 0.001)], abortion history [OR:2.54 (95% CI:1.69–3.86) (P < 0.001)] and prolonged breastfeeding [OR:2.01 (95% CI:1.63–2.49) (P < 0.001)] increase the chance of breast cancer. On the other hand, increasing education level [OR: 0.34 (95% CI:0.28–0.42) P < 0.001] and regular menstrual cycles [OR:0.61 (95% CI:0.39–0.95) (P = 0.030)] get less breast cancer. Our study demonstrated that stress and mental pressure, increasing age, and menopause status increased the risk of breast cancer; in contrast, increasing education level and regular menstrual cycles decreased breast cancer risk.
 
Keywords: Breast cancer, Risk factors, Reproductive, Stress, Gravida
 
 
Expression analysis of cell cycle related lncRNAs in breast cancer tissues
 

Abstract

Cell cycle regulation is an important cellular function. Abnormal regulation of this process can cause cancer. Several genes are involved in this process. There is no comprehensive study on expression pattern of cell cycle related lncRNAs in breast cancer patients. In the current study, we evaluated expressions of LINC00668, PRDM16-DT, SNHG7 and CDKN2A in 42 pairs of breast cancer tissues and adjacent non-tumoral tissues. Expression of SNHG7 was significantly lower in tumoral tissues compared with non-tumoral tissues. However, expressions of LINC00668, PRDM16-DT and CDKN2A were not significantly different between these two sets of samples. Expression levels of SNHG7 could separate tumoral tissues from non-tumoral tissues with AUC value= 0.66, sensitivity= 61% and specificity= 73%. Expression of CDKN2A was associated with clinical stage (P value=0.01). Expression levels of LINC00668, PRDM16-DT, SNHG7 and CDKN2A were higher in estrogen receptor (ER) positive samples compared with ER negative ones (P values=0.044, 0.008, 0.002 and 0.022, respectively). Moreover, expression of SNHG7 was higher in progesterone receptor (PR) positive samples compared with PR negative ones (P value=0.02). Finally, expressions of PRDM16-DT, SNHG7 and CDKN2A were higher in HER2/neu positive samples compared with HER2/neu negative ones (P values=0.017, 0.02 and 0.021, respectively). Taken together, our study demonstrates possible roles of these genes in breast cancer and warrants further functional studies.

DOI: https://doi.org/10.1016/j.prp.2023.154453

Feasibility and Outcomes of Temporary Bulbar Urethral Stent Placement After Internal Urethrotomy in the Largest Multicenter Series

Abstract
Background
Recent years have seen the development of a new generation of temporary urethral stents as an adjuvant option after direct vision internal urethrotomy (DVIU). Despite some early promising results, large series addressing their safety and outcomes are still lacking.
 
Objective
To report complications and outcomes from the largest series of patients receiving a temporary bulbar urethral stent to date.
 
Design, setting, and participants
We performed a retrospective analysis of bulbar urethral stenting procedures after DVIU in seven centers. Patients either refused urethroplasty or were not fit for surgery. The stents were removed after at least 6 mo in place unless complications requiring earlier removal occurred.
 
Surgical procedure
DVIU with a cold knife or laser is performed, followed by stent placement. At the end of the treatment period, the stent is removed under cystoscopy with gripping forceps.
 
Measurements
All patients underwent postoperative follow-up (FU) for assessment of complications while the stent was in place. After removal, the FU schedule consisted of office evaluation at 6 mo and 12 mo, and then annually. Failure was defined as any treatment for urethral stricture after stent removal.
 
Results and limitations
A total of 49% of the patients experienced complications. The most frequent were discomfort (23.8%), stress incontinence (17.5%), and stent dislocation (9.8%). Some 85% of the adverse events observed were Clavien-Dindo grade <3. The overall success rate at median FU of 38.2 mo was 76.9%. The success rate was significantly lower if the stent was removed before 6 mo (53.3% vs 79.7%; p = 0.026).
 
Conclusions
Temporary urethral stents may be a safe choice with satisfactory results in patients not undergoing urethroplasty. A stent indwelling time shorter than 6 mo provides worse outcomes that are comparable to those with DVIU alone.
 
Patient summary
We assessed complications and outcomes after placement of a temporary narrow tube in the urethra after surgery to widen a narrowing of the urethra. The treatment is safe and easily reproducible with satisfactory results. Further studies are needed to confirm our findings.
 
 

Perspectives on the future of urothelial carcinoma therapy: chemotherapy and beyond

Abstract
 
Introduction: Despite recent developments in the landscape of urothelial carcinoma (UC) treatment, platinum combination chemotherapy still remains a milestone. Recently immunotherapeutic agents have gained ever-growing attractivity, particularly in the metastatic setting. Novel chemotherapeutic strategies and agents, such as antibody-drug conjugates (ADCs), and powerful combination regimens have been developed to overcome the resistance of most UC to current therapies.
Areas covered: Herein, we review the current standard-of-care chemotherapy, the development of ADCs, the rationale for combining therapy regimens with chemotherapy in current trials, and future directions in UC management.
Expert opinion: Immunotherapy has prompted a revolution in the treatment paradigm of UC. However, only a few patients experience a long-term response when treated with single-agent immunotherapies. Combination treatments are necessary to bypass resistance mechanisms and broaden the clinical utility of current options. Current evidence supports the intensification of standard-of-care chemotherapy with maintenance immunotherapy. However, the optimal sequence, combination, and duration must be determined to achieve individual longevity with acceptable health-related quality of life. In that regard, ADCs appear as a promising alternative for single and combination strategies in UC, as they specifically target the tumor cells, thereby, theoretically improving treatment efficacy and avoiding extensive off-target toxicities.
Keywords: antibody-drug conjugates; bladder cancer; chemotherapy; combination therapy; epigenetic modifiers; immunoconjugates; peptide-drug conjugates; targeted therapy; upper tract urothelial carcinoma; urothelial carcinoma.
 

Iatrogenic ureteric injury during abdominal or pelvic surgery: a meta-analysis

Abstract
 
Objective: To assess the incidence of ureteric injuries, clinical value of prophylactic ureteric stenting and impact of intra- or postoperative detection of ureteric injuries in patients treated with gynaecological or colorectal surgery.
Methods: Multiple databases were searched for articles published before September 2021 according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Studies were deemed eligible if they evaluated the differences in the rate of ureteric injuries between laparoscopic and open surgery, prophylactic ureteric stenting or not, and those of final treatment success between intra- and postoperative detection in patients who underwent gynaecological or colorectal surgery.
Results: Overall, 46 studies were eligible for this meta-analysis. Compared to open surgery, laparoscopic hysterectomy was associated with a higher incidence of ureteric injuries (pooled odds ratio [OR] 2.12, 95% confidence interval [CI] 1.71-2.62), but there was no statistically significant difference in colectomy (pooled OR 0.89, 95% CI 0.77-1.03). Prophylactic ureteric stenting was associated with a lower incidence of ureteric injuries during gynaecological surgery (pooled OR 0.61, 95% CI 0.39-0.96). The number needed to perform ureteric stenting to prevent one ureteric injury was 224 in gynaecological surgery. On the other hand, prophylactic ureteric stenting did not reduce the risk of ureteric injuries during colorectal surgery. Intraoperative detection of a ureteric injury was associated with a lower rate of complication management failure compared to postoperative detection (pooled OR 0.22, 95% CI 0.12-0.41).
Conclusions: Laparoscopic hysterectomy seems to be associated with a higher rate of ureteric injuries compared to an open approach. Prophylactic ureteric stenting seems to reduce this risk during gynaecological surgery. Intraoperative detection of a ureteric injury during abdominal/pelvic surgery improves outcomes, suggesting the need for awareness and proactive problem identification. Further well-designed studies assessing the candidates who are more likely to benefit from prophylactic ureteric stenting including cost analysis are needed.
 
Keywords: #UroTrauma; #Urology; colectomy; hysterectomy; iatrogenic; laparoscopic; ureteric injury; ureteric stent.
 

Meteorin-like Protein and Asprosin Levels in Children and Adolescents with Obesity and Their Relationship with Insulin Resistance and Metabolic Syndrome

Abstract
 
Objective: Two newly discovered adipokines, including Meteorin-like protein (Metrnl) and asprosin, have been implicated in glucose and insulin metabolism. This study aimed to investigate the associations of these adipokines with obesity in children and adolescents.
Methods: This study was performed on 35 normal-weight children and 35 children with obesity. Anthropometric and biochemical parameters were determined. Serum concentrations of Metrnl, asprosin, and insulin were measured using enzyme-linked immunosorbent assay.
Results: Metrnl level was significantly lower in obese children than normal-weight children. Additionally, Metrnl was negatively correlated with body mass index (BMI), insulin, waist-to-hip ratio, and homeostatic model assessment of insulin resistance (HOMA-IR). Our results also revealed that circulating asprosin levels were significantly increased in obese children compared to the control subjects and were positively correlated with BMI, insulin, HOMA-IR, cholesterol, and LDL-C.
Conclusion: Obesity is accompanied by significant alterations in Metrnl and asprosin and therefore these adipokines, especially Metrnl, are suggested as new promising therapeutic targets for obesity and its associated metabolic imbalances.
 
Keywords: Metrnl; asprosin; children; insulin resistance; metabolic syndrome; obesity.
 

DOI: 10.1093/labmed/lmac152

Expression analysis of cytoskeleton regulator RNA and Cyclin Dependent Kinase Inhibitor 2B genes in breast cancer

Abstract
 
Background: Breast cancer has been found to be associated with deregulation of several non-coding genes and mRNA coding genes.
Objective: To assess expressions of CYTOR and CDKN2B in breast cancer and adjacent samples and find their relevance with clinical data.
Methods: We enumerated expression level of CDKN2B and CYTOR in 43 newly diagnosed breast cancer samples and their adjacent specimens using real-time PCR method Expression data was judged using Wilcoxon matched-pairs signed rank test.
Results: CYTOR level was higher in tumors compared with adjacent tissues. Nevertheless, there was no difference in expression of CDKN2B between these two sets of tissues. ROC curve analysis showed that CYTOR levels can differentiate between tumoral and adjacent tissues with AUC, specificity and sensitivity values of 0.65, 37% and 92% (P= 0.017). There was a positive correlation between expression levels of CYTOR and CDKN2B genes in breast cancer tissues (r= 0.5 and P= 0.0008) as well as adjacent tissues (r= 0.79 and P< 0.0001). Relative expression level of CDKN2B in normal tissues was associated with clinical stage (P= 0.014). Moreover, relative expression level of CDKN2B in tumor tissues was associated with the body weight. There was no other association between expressions of CYTOR and CDKN2B and clinical or pathological variables.
Conclusions: Cumulatively, this study offers evidence for involvement of these genes in the pathoetiology of breast cancer.
 
Keywords: Breast cancer; CDKN2B; CYTOR.
 
 

Frequency of Post Trauma Complications during Hospital Admission and its Association with Injury Severity Score (ISS)

Abstract
 
Objectives: Multiple trauma is associated with a remarkable risk of in-hospital complications, which harmhealthcare services and patients. This study aimed to assess the incidence of post-trauma complications, their relationship with poor outcomes, and the effect of injury severity score (ISS) on their occurrence.
Methods: This retrospective cohort study was conducted at two trauma centers, between January 2020 and December 2022. All hospitalized adult patients with multiple trauma were included in this study. Multivariable logistic regression was used to find factors related to post-trauma complications.
Results: Among 727 multiple trauma patients, 90 (12.4%) developed in-hospital complications. The most frequent complications were pneumonia (4.8%), atelectasis (3.7%), and superficial surgical site infection (2.5%). According to multivariable logistic regression, ISS, ICU length of stay, hospital length of stay, and mortality were significantly associated with complications. The complication rate increased by 17% with every unit increase in ISS (adjusted odds ratio=1.17, 95% CI= 1.00-1.38). Per one-day longer stay in ICU and hospital, the complication rate increased by 65% (adjusted odds ratio=1.65, 95% CI= 1.00-2.73) and 20% (adjusted odds ratio=1.20, 95% CI= 1.03-1.41), respectively. The post-trauma complication was also 163 times higher in patients with mortality (adjusted odds ratio=163.30, 95% CI= 3.04-8779.32). In higher ISS, the frequency, severity, and number of complications significantly increased in multiple trauma patients.
Conclusions: In-hospital complications in multiple trauma patients were frequent and associated with poor outcome and mortality. ISS was an important factor associated with post-trauma complications.
 
Keywords: Complications; Failure to Rescue; Multiple Trauma; Trauma Severity Indices; Wounds and Injuries.
 
  • Impact of Performance Status on Oncologic Outcomes in Patients with Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitor: A Systematic Review and Meta-analysis

 

Abstract

Context: Immune checkpoint inhibitors (ICIs) are widely used in the management of patients with advanced urothelial carcinoma (aUC). However, its performance in aUC patients with poor performance status (PS) remains unknown.
Objective: We aimed to assess the impact of patients' performance status on the oncologic outcomes in patients with aUC treated with ICIs.
Evidence acquisition: We searched PubMed, Web of Science, and Scopus from inception until July 2022 to identify studies assessing the association between the Eastern Cooperative Oncology Group (ECOG) PS and the oncologic outcomes in patients with aUC treated with ICIs in randomised (RCTs) and nonrandomised (NRCTs) control studies according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The outcomes of our interests were overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rate (ORR).
Evidence synthesis: Overall, six RCTs comprising 5428 patients and 32 NRCTs comprising 6069 patients were included. The meta-analysis of the RCTs revealed that patients with ECOG PS = 0 and PS ≥1 had a trend towards better OS with ICIs compared with those treated with chemotherapy (pooled hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.71-1.04, and HR: 0.74, 95% CI: 0.53-1.03, respectively). There was no significant difference in terms of response to ICIs between patients with poor and good PS (I2 = 0%, p = 0.46). The meta-analysis of the NRCTs revealed that patients with PS ≥2 had significantly worse OS than those with PS <2 (pooled HR: 2.52, 95% CI: 2.00-3.17), as well as worse CSS (pooled HR: 3.35, 95% CI: 1.90-5.91), PFS (pooled HR: 2.89, 95% CI: 1.67-5.01), and ORR (pooled odds ratio: 0.47, 95% CI: 0.27-0.82). Similarly, patients with PS ≥1 had significantly worse oncologic outcomes than those with PS = 0.
Conclusions: In the NRCTs, poor PS was correlated with worse oncologic outcomes in aUC patients treated with ICIs. In the RCTs, ICIs performed better than chemotherapy across all PS categories. These findings should be interpreted with caution due to the high heterogeneity across the studies and patient populations. More RCTs including poor PS are needed to assess the impact of PS on ICI therapy outcomes.
Patient summary: Immune therapy for patients with urothelial carcinoma should not be restricted on the grounds of performance status. However, patients with poor performance status should be considered for other factors such as life expectancy and comorbidities.
 
Keywords: Eastern Cooperative Oncology Group; Immune checkpoint inhibitor; Performance status; Urothelial carcinoma.
 

DOI: 10.1016/j.euf.2023.01.019

Altered expression of long noncoding RNAs and p53 as a possible genetic signature in luminal A invasive breast ductal carcinoma

Abstract
 
Introduction: Breast cancer is the second most common cause of cancer-related death among females. The long non-coding RNAs (lncRNAs) are a significant population of non-coding RNAs with well-defined functions in both adjacent normal cells and tumorigenesis. Miss expression of them has been associated with the development of different kinds of cancers.
Purpose: The aim of this study was to investigate the alterations in 3 lncRNAs and p53 in tissue samples of a group of women with luminal type A breast adenocarcinoma.
Material and method: In this case-control study, the expression levels of p53 and three lncRNAs were evaluated in association with luminal A breast cancer in 80 ductal carcinoma tumors and adjacent normal breast tissues.Quantitative real-time PCR was used to measure the expression of the mentioned genes. The data were analyzed using t-tests.
Result: The expression levels of IGFBP7-AS1, and RHPN1-AS1, showed a significant increase (P>0.05) while P53 and LINC00861 had a significant decrease in expression level in tumor tissues compared to adjacent normal tissues (P> 0.05). Receiver Operating Characteristic (ROC) curve indicated the diagnostic power of LINC00861 in differentiating tumor tissues from adjacent normal tissue with 90% sensitivity and 96% specificity, which can also interact with P53.Based on the area under the curve (AUC) value, expression of Linc00861, p53, RHPN1-AS1, and IGFBP-AS1 genes can help to differentiate patients from healthy individuals with diagnostic power of 0/855, 0/824, 0/778, and 0/659, respectively.
Conclusion: The key roles of the latest genes in the control of cancer-related pathways and the dysregulation of their expression in studied malignancies imply that they can be exploited as biomarkers for cancer diagnosis, prognosis, and possible therapeutic targets. Here, the roles of lncRNAs in invasive breast ductal carcinoma type luminal A and their importance in prognosis and patient treatment are discussed.
 
Keywords: breast cancer , long non-coding RNA , prognostic biomarker
 
 

Kisspeptin decreases the adverse effects of human ovarian vitrification by regulating ROS-related apoptotic occurrences

Abstract
 
Kisspeptin is characterized as a neuropeptide with a pivotal function in female and male infertility, and its antioxidant properties have been demonstrated. In this study, the effects of kisspeptin on the improvement of the vitrification and thawing results of human ovarian tissues were investigated. In this work, 12 ovaries from patients who underwent hysterectomy were collected laparoscopically, and then 32 samples from each of their tissues were taken. Haematoxylin and eosin (H&E) staining was performed to check the normality of the ovarian tissue and, subsequently, the samples were allocated randomly into four groups, including: (1) fresh (control), (2) vitrification, (3) vitrified + 1 μM kisspeptin, and (4) vitrified + 10 μM kisspeptin groups. After vitrification, thawing, and tissue culture processes, H&E staining for tissue quality assessment, terminal deoxynucleotidyl transferase dUTP nick end labelling assay for apoptosis evaluation, and malondialdehyde (MDA), superoxide dismutase (SOD), and ferric reducing ability of plasma tests for oxidative stress appraisal were carried out. Our histological results showed incoherency of ovarian tissue morphology in the vitrification group compared with other groups. Other findings implicated increased apoptosis rate and MDA concentration and reduced SOD activity and total antioxidant capacity (TAC) in the vitrification group compared with the control group (P < 0.05). Moreover, decreased apoptosis rate and MDA concentration, and increased TAC and SOD function were observed in the vitrification with kisspeptin groups (1 μM and 10 μM) compared with the vitrified group (P < 0.05). Our reports express that kisspeptin is an effective agent to overcome the negative effects of vitrification by regulating reactive oxygen species-related apoptotic processes.
 
Keywords: Apoptosis; Human ovarian cryopreservation; Kisspeptin; Oxidative stress.
 

Association of fertility diet score with endometriosis: a case-control study

Abstract
 
Background and aims: Different factors, such as environmental, epigenetic, genetic and immunological, have been identified as potential risks for developing endometriosis. However, the correlation between dietary patterns and endometriosis is currently unknown. The aim of this study was to explore the potential link between fertility diet score and the odds of endometriosis.
 
Methods: This study was a hospital-based case-control study that took place in a gynecology clinic in Tehran, Iran, between February 2021 and January 2022. A total of 107 newly diagnosed endometriosis cases and 210 controls were included. The participants' habitual diets were evaluated using a food frequency questionnaire, and their fertility diet score was estimated using a point system based on Chavarro et al.'s criteria. The logistic regression was utilized to calculate the odds ratios (OR) with 95% confidence intervals (CIs).
 
Results: The study found that women who adherence to fertility diet have a lower odds of endometriosis. This was observed in both the base model and the adjusted model, with a significant decrease in odds of endometriosis by 66% (OR = 0.44, 95%CI = 0.27-0.71, p = 0.001) and 54% (aOR = 0.46, 95%CI = 0.23-0.90, p = 0.022), respectively. Additionally, consuming vegetable proteins and multivitamins were also associated with lower odds of endometriosis. On the other hand, consuming animal proteins, heme iron, and having a high glycemic load were associated with significantly higher odds of endometriosis.
 
Conclusion: Our research supports the hypothesis that following a fertility diet may decrease the odds of endometriosis in Iranian women. However, these findings should be verified through extensive, prospective studies.
 
Keywords: case-control; dietary assessment; endometriosis; fertility diet score; women.
 

The effect of kisspeptin on the maturation of human ovarian follicles in culture following vitrification-thawing processes

Abstract
 
Objective: Ovarian cryopreservation is one of the effective methods to preserve fertility for cancer patients. Still, this approach has some problems, namely ROS, resulting in adverse effects on oocytes and ovarian follicles. Kisspeptin as an antioxidant to control ovarian function, directly or indirectly. In this study, the effect of kisspeptin on follicle maturation was evaluated in culture following ovarian cryopreservation. 
Methods: Ovarian tissue samples of women between 20 and 35 years old (n=12) were laparoscopically collected. The samples were randomly divided into four groups: 1) control, 2) vitrification, 3) vitrified+1μM kisspeptin, and 4) vitrified+10μM kisspeptin. After vitrification and thawing processes, the tissues were cultured in DMEM medium for 7 days. H&E staining for histological evaluation, Real-Time PCR for GDF9 and BMP15 gene expression, and immunohistochemical staining for GDF9 and BMP15 protein expression were performed.
Results: In the vitrification group, ovarian tissue morphology was incoherent, and more primordial follicles than other follicle types were found. The expression of GDF9 and BMP15 genes and proteins were significantly decreased in this group compared with other groups (p<0.05). In the vitrification groups with kisspeptin (1 and 10 μM), the number of primary and secondary follicles was more than in the vitrification group. Besides, the expression of these genes and proteins was dramatically elevated in the vitrification groups with kisspeptin compared to the vitrification group alone (p<0.05).
Conclusions: It seems that kisspeptin is an effective substance to improve the quality of the human ovarian cryopreservation medium by improving follicle maturation.
 
Keywords: BMP15; GDF 9; follicle maturation; human ovarian cryopreservation; kisspeptin.
 

Comparison of outcomes and complications in conventional versus ultrasound-accelerated catheter directed thrombolysis for treatment of pulmonary embolism: A systematic review and meta-analysis

Abstract
 
Background: Acute submassive a massive pulmonary embolism are known as leading causes of cardiovascular morbidity and mortality in emergency departments. Choosing the optimal type of catheter directed thrombolysis (CDT) for treatment of pulmonary embolism presents a quandary to the practitioners. To the best of our knowledge, there is no meta-analysis comparing superiority of conventional CDT and ultrasound-accelerated catheter directed thrombolysis (USACDT). Therefore, in this meta-analysis, we aimed to compare conventional CDT with USACDT regarding clinical outcomes and safety profile.
Methods: A systematic literature search of previous published studies comparing conventional CDT with USACDT regarding clinical outcomes and safety profile was carried out in the electronic databases including MEDLINE, Scopus, EBSCO, Google Scholar, Web of Science, and Cochrane from inception to December 2021. Data were analyzed by comprehensive meta-analysis software (CMA, version 3).
Results: The meta-analysis included nine studies with a total of 705 patients. Our meta-analysis showed that there is no significant difference between two groups with respect to pulmonary arterial systolic pressure (SMD: -0.084; 95% CI: -0.287 to 0.12; p: 0.41), RV/LV (SMD: -0.003; 95% CI: -0.277 to 0.270; p: 0.98), and Miller score (SMD: -0.345; 95% CI: -1.376 to 0.686; p: 0.51). Similarly, we found no statistically significant differences between two groups regarding major and minor bleeding (p > .05).
Conclusion: Our meta-analysis showed that when compared with USACDT, conventional CDT provides similar clinical and hemodynamic outcomes or safety for treatment of pulmonary embolism without the need for very expensive technologies. However, randomized clinical trials are required to further investigate cost-effectiveness of USACDT in comparison with conventional CDT.
 
Keywords: Pulmonary embolism; bleeding; catheter-directed thrombolysis; meta-analysis; ultrasound-accelerated thrombolysis.
 

Expression of NF-κB-associated lncRNAs in different types of migraine

Abstract
 
Purpose: NF-κB partakes in the pathophysiology of neurologic conditions. We quantified levels of NF-κB-associated genes in 119 patients with migraine versus healthy controls.
Methods: We measured levels of NF-κB-associated genes in 42 patients with migraine compared with age- and sex-matched controls.
Results: Comparison between patients without aura and controls revealed down-regulation of PACER [expression ratio (95% CI) 0.15 (0.06-0.36), P value < 0.0001]. Similar results were detected when comparing expression of PACER in patients with aura and controls [expression ratio (95% CI) 0.05 (0.02-0.12), P value < 0.0001]. Both DILC and CEBPA were over-expressed in patients with aura [expression ratio (95% CI) 4.9 (2.96-7.83), P value < 0.0001 and expression ratio (95% CI) 3.65 (2.39-5.24), P value < 0.0001, respectively] and in patients without aura compared with controls [expression ratio (95% CI) 3.6 (2.21-5.69), P value < 0.0001 and expression ratio (95% CI) 4.5 (2.53-7.11), P value < 0.0001, respectively]. ADINR was over-expressed in patients with aura [expression ratio (95% CI) 4.98 (3.09-8.33), P value < 0.0001] as well as patients without aura compared with controls [expression ratio (95% CI) 13.15 (7.41-23.58), P value < 0.0001]. Notably, ADINR levels were lower in patients with aura compared with patients without aura. When comparing ATG5 levels in patients with aura and controls, significant up-regulation was detected [expression ratio (95% CI) 4.4 (3.01-6.32), P value < 0.0001]. This pattern was also detected in patients without aura compared with controls [expression ratio (95% CI) 3.5 (2.28-5.35), P < 0.0001]. Finally, expression of DICER1-AS1 was elevated in patients with aura compared with patients without aura [expression ratio (95% CI) 2.47 (1.14-5.85), P = 0.03]. This lncRNA was under-expressed in patients without aura compared with controls [expression ratio (95% CI) 0.4 (0.21-1.31), P = 0.03]. CEBPA, ATG5 and ADINR had the best AUC values for distinguishing patients with aura from controls (AUC values = 0.91, 0.85 and 0.83, respectively). The AUC values for separation between patients without aura and controls were 0.90, 0.86 and 0.75 for CEBPA, ATG5 and ADINR, respectively.
Conclusion: Taken together, several genes in the NF-κB pathway has been revealed to be dysregulated in migraineurs and expression of these genes can be used as markers for this neurological condition.
 
Keywords: ADINR; ATG5; Aura; CEBPA; Migraine.
 

Characterization of vaginal Lactobacillus species as a predictor of fertility among Iranian women with unexplained recurrent miscarriage and fertile women without miscarriage history using machine learning modeling

Abstract
 
Background: Lactobacillus spp. are the predominant bacteria of the vaginal tract, the alteration of which has been previously linked to miscarriage. Here, we investigated differences between selected vaginal Lactobacillus species of women with a history of recurrent miscarriages and fertile women without a history of miscarriage in Iran.
Methods and results: Vaginal swabs were taken from 29 fertile and 24 infertile women and quantitative real-time PCR (qPCR) assay was used to determine a selection of vaginal Lactobacillus species in both groups. The logistic regression (LR) model, Naive Bayes (NB) model, support vector machine model (SVM), and neural network model (NN) were developed to predict disease outcome by selected variables. LR analysis was used to construct a nomogram indicating predictions of the risk of miscarriage. The most abundant species among the patients were L. rhamnosus, L. ruminis, and L. acidophilus, while L. gasseri, L. vaginalis, L. fermentum, and L. iners were more abundant in healthy subjects. The distribution of L. ruminis, L. iners, and L. rhamnosus was higher in patients, while L. acidophilus, L. gasseri, and L. fermentum were highly distributed among healthy subjects. Higher AUC in predicting the disease outcome was observed for L. gasseri, L. rhamnosus, L. fermentum, and L. plantarum.
Conclusion: Our findings provide experimental evidence of vaginal Lactobacillus imbalance in infertile women and a suitable predictor for miscarriage based on the AUC algorithms. Further studies with larger sample size and using high-throughput technologies are needed to boost our understanding of the role of lactobacilli in miscarriage.
 
Keywords: Infertility; Machine learning; Prediction models; Recurrent miscarriage; Vaginal Lactobacillus species.
 

Novel repair of acute Stanford type B aortic dissection using combined endovascular graft and transfemoral replacement of vascular plug

Abstract
 
We present successful treatment of dissected thoracoabdominal aorta using combined thoracic endovascular aortic repair and transfemoral replacement of Amplatzer™ vascular plug in a 38-year-old patient. Computed tomography angiography revealed a false lumen from the left subclavian artery to the left common iliac trunk, with re-entries connecting it to the true lumen of the aorta. We replaced the prosthetic endovascular graft just below the left subclavian artery to the top of the superior mesenteric artery. Amplatzer™ vascular plug was replaced below the diaphragm in a closed transfemoral procedure to prevent re-entry. The patient was discharged in good condition and 2 years postoperation imaging showed complete pseudoaneurysm closure.
 
Keywords: AMPLATZER septal occluder; TEVAR; aortic dissection; endovascular graft; pseudoaneurysm.
 

Effects of Electrospun Nanofibers on Motor Function Recovery After Spinal Cord Injury: A Systematic Review and Meta-Analysis

Abstract
 
Nanofibers made by electrospinning have been used as bridging materials in animal models to regenerate nerves after spinal cord injury (SCI). In this meta-analysis study, we investigated the effect of these nanofibers on the motor function of animals after SCI. An extensive search in databases was performed. After primary and secondary screening, data included functional behavior, expression of glial fibrillary acidic protein, neurofilament-200 (NF-200), and β-tubulin III were taken from the articles. The quality control of the articles, statistical analysis, and subgroup analysis were performed. The results from 14 articles and 16 separate experiments showed that electrospun nanofibers used alone could improve motor behavior and reduce glial injury after SCI.
 
Keywords: Animal models; Electrospinning; Functional recovery; GFAP; Neurofilament-200; Polymeric nanofibers; Spinal cord injury.
 
  

Characterization of vaginal Lactobacillus species as a predictor of fertility among Iranian women with unexplained recurrent miscarriage and fertile women without miscarriage history using machine learning modeling

Abstract
 
Background: Lactobacillus spp. are the predominant bacteria of the vaginal tract, the alteration of which has been previously linked to miscarriage. Here, we investigated differences between selected vaginal Lactobacillus species of women with a history of recurrent miscarriages and fertile women without a history of miscarriage in Iran.
 
Methods and results: Vaginal swabs were taken from 29 fertile and 24 infertile women and quantitative real-time PCR (qPCR) assay was used to determine a selection of vaginal Lactobacillus species in both groups. The logistic regression (LR) model, Naive Bayes (NB) model, support vector machine model (SVM), and neural network model (NN) were developed to predict disease outcome by selected variables. LR analysis was used to construct a nomogram indicating predictions of the risk of miscarriage. The most abundant species among the patients were L. rhamnosus, L. ruminis, and L. acidophilus, while L. gasseri, L. vaginalis, L. fermentum, and L. iners were more abundant in healthy subjects. The distribution of L. ruminis, L. iners, and L. rhamnosus was higher in patients, while L. acidophilus, L. gasseri, and L. fermentum were highly distributed among healthy subjects. Higher AUC in predicting the disease outcome was observed for L. gasseri, L. rhamnosus, L. fermentum, and L. plantarum.
 
Conclusion: Our findings provide experimental evidence of vaginal Lactobacillus imbalance in infertile women and a suitable predictor for miscarriage based on the AUC algorithms. Further studies with larger sample size and using high-throughput technologies are needed to boost our understanding of the role of lactobacilli in miscarriage.
 
Keywords: Infertility; Machine learning; Prediction models; Recurrent miscarriage; Vaginal Lactobacillus species.
 

Novel repair of acute Stanford type B aortic dissection using combined endovascular graft and transfemoral replacement of vascular plug

Abstract
 
We present successful treatment of dissected thoracoabdominal aorta using combined thoracic endovascular aortic repair and transfemoral replacement of Amplatzer™ vascular plug in a 38-year-old patient. Computed tomography angiography revealed a false lumen from the left subclavian artery to the left common iliac trunk, with re-entries connecting it to the true lumen of the aorta. We replaced the prosthetic endovascular graft just below the left subclavian artery to the top of the superior mesenteric artery. Amplatzer™ vascular plug was replaced below the diaphragm in a closed transfemoral procedure to prevent re-entry. The patient was discharged in good condition and 2 years postoperation imaging showed complete pseudoaneurysm closure.
 
Keywords: AMPLATZER septal occluder; TEVAR; aortic dissection; endovascular graft; pseudoaneurysm.
 

Role of clinicopathological variables in predicting recurrence and survival outcomes after surgery for non-metastatic renal cell carcinoma: Systematic review and meta-analysis

Abstract
 
Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta-analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post-surgery survival outcomes in non-metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body-mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence-free survival (RFS) and cancer-specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C-reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high-risk RCC patients and enhancing the development of more precise prediction models.
 
Keywords: RCC; clinicopathological; late recurrence; recurrence; survival.
 

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