Patients with gynecological malignancies are similar to other IVF patients without cancer for clinical and molecular reproductive parameters and DNA damage response pattern.

This study intended to investigate if gynecological cancers compromise ovarian function and reduce the success of assisted reproduction techniques (ART). No clinical and molecular data together is available on this issue for gynecological or other organ cancers. Steroidogenic pathways and DNA damage response characteristics of the granulosa cells retrieved from the 39 gynecological cancer patients were analyzed together with their clinical ART characteristics in comparison to 31 control ART patients. Patients with gynecological malignancies were similar to the control IVF patients for the number of mature oocytes retrieved, fertilization rates and embryo development competency. Molecular analyses of the granulosa cells retrieved from these cancer patients did not detect any perturbations in gonadotropin receptor expression and response, sex steroid production, cholesterol utilization/storage and, DNA damage response pattern in comparison to control IVF patients without cancer. This study provides the first reassuring clinical and molecular combined data set that the presence of gynecological malignancy does not appear to have any detrimental effect on clinical IVF cycle characteristics and ovarian functioning at molecular level.

BNT162b2 or CoronaVac as the Third Dose against Omicron: Neutralizing Antibody Responses among Transplant Recipients Who Had Received Two Doses of CoronaVac.

We evaluated neutralizing antibodies against the Omicron variant and Anti-Spike IgG response in solid organ (SOT) or hematopoietic stem cell (HSTC) recipients after a third dose of BNT162b2 (BNT) or CoronaVac (CV) following two doses of CV. In total, 95 participants underwent SOT (n = 62; 44 liver, 18 kidney) or HSCT (n = 27; 5 allogeneic, 22 autologous) were included from five centers in Turkey. The median time between third doses and serum sampling was 154 days (range between 15 to 381). The vaccine-induced antibody responses of both neutralizing antibodies and Anti-Spike IgGs were assessed by plaque neutralizing assay and immunoassay, respectively. Neutralizing antibody and Anti-Spike IgG levels were significantly higher in transplant patients receiving BNT compared to those receiving CV (Geometric mean (GMT):26.76 vs. 10.89; p = 0.03 and 2116 Au/mL vs. 172.1 Au/mL; p < 0.001). Solid organ transplantation recipients, particularly liver transplant recipients, showed lower antibody levels than HSCT recipients. Thus, among HSCT recipients, the GMT after BNT was 91.29 and it was 15.81 in the SOT group (p < 0.001). In SOT, antibody levels after BNT in kidney transplantation recipients were significantly higher than those in liver transplantation recipients (GMT: 48.32 vs. 11.72) (p < 0.001). Moreover, the neutralizing antibody levels after CV were very low (GMT: 10.81) in kidney transplantation recipients and below the detection limit (<10) in liver transplant recipients. This study highlights the superiority of BNT responses against Omicron as a third dose among transplant recipients after two doses of CV. The lack of neutralizing antibodies against Omicron after CV in liver transplant recipients should be taken into consideration, particularly in countries where inactivated vaccines are available in addition to mRNA vaccines.

Can remote ischemic preconditioning counteract the renal functional deterioration attributable to partial nephrectomy under warm ischemia? Results of an animal study.

BACKGROUND: To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. METHODS: Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. RESULTS: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). CONCLUSION: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.

Immune profiling after minimally invasive lobectomy.

OBJECTIVES: Whether acute phase and immune responses are minimally affected following minimally invasive lung surgery needs further investigation. We performed a pilot study to evaluate the immune profile of patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracic surgery lobectomies for the treatment of suspicious or known stage I non-small-cell lung cancer. METHODS: Blood samples were taken preoperatively and 3 and 24 h postoperatively were analysed for C-reactive protein, glucose, cortisol, tumour necrosis factor alpha (TNF-α), interleukin 8 (IL-8) and interleukin 10 (IL-10) levels. TNF-α, IL-8 and IL-10 were also measured in lung tissues. T (CD4, CD8), B (CD19) and natural killer (CD56, CD16) cell counts and natural killer cell functions were analysed using a flow cytometry-based assay before and after surgery. RESULTS: Minimally invasive surgery (robot-assisted thoracic surgery + video-assisted thoracoscopic surgery) significantly decreased IL-10 (P = 0.016) levels after surgery. No significant differences were detected in TNF-α (P = 0.48) and IL-8 (P = 0.15) levels before and after surgery. C-reactive protein (P < 0.001), cortisol (P < 0.001) and glucose levels (P < 0.001) increased significantly after surgery. Lymphocyte, total T cell, CD3+CD4+ and CD3+CD8+ CD16+CD56+ cell counts were significantly lower on postoperative day 1. CONCLUSION: There seems to be a dynamic balance between pro- and anti-inflammatory cytokines and immune cells following minimally invasive lobectomy.

Terminal differentiation of human granulosa cells as luteinization is reversed by activin-A through silencing of Jnk pathway.

Molecular mechanisms underlying luteinization (terminal differentiation of granulosa and theca cells after ovulation) and luteolysis (demise of corpus luteum) are poorly understood in human ovary. Here we report that activin-A, after binding to its cognate receptors induces a functional luteolytic state and reverses luteinization phenotype by downregulating the expression of the steroidogenic enzymes, LH receptor and VEGF and reducing estradiol (E2) progesterone (P4) production and upregulating FSH receptor and cyclin D1 expression in human primary luteinized granulosa cells. Further, this action of activin-A involves downregulation of JNK signaling pathway and is opposite to that of human chorionic gonadotropin (hCG), which acts as a luteotropic hormone and improves luteal function through the activation of JNK pathway in the same cell type. Reversal of luteinization phenotype in luteal granulosa cells by activin-A potentially makes this hormone an attractive candidate for use under certain clinical situations, where induction of luteolysis and rapid reduction of endogenous sex steroid levels are beneficial such as ovarian hyperstimulation syndrome (OHSS), in which the ovaries hyper-respond to gonadotropin stimulation by producing too many growing follicles along with development of ascites, pleural effusion, and hemo-concentrations as a result of increased vascular permeability and leakage of intravascular volume into third spaces. Our work unveils a previously undefined role for activin-A and JNK signaling pathway in human corpus luteum biology, that might have a direct clinical impact in assisted reproductive technologies.

In-vitro AMH production of ovarian tissue samples in culture correlates with their primordial follicle pool.

OBJECTIVE: We aimed to investigate if there is a correlation between in-vitro AMH production and primordial follicle reserve of the ovarian cortical samples in culture. METHODS: Seven patients undergoing laparoscopic excision of ovarian dermoid cysts were included in the study. 0.5 × 0.5 cm of ovarian cortical samples embedded within the cyst wall were removed and cultured for one day. Then, the cultured cortical pieces were fixed, paraffin-embedded and serially sectioned for histormorphometric analysis. AMH and estradiol (E2) production of the samples after one-day culture period were measured in the spent culture media. Primordial follicle density was expressed as the number of primordial follicles per mm2. Pearson correlation and linear regression analyses were applied. RESULTS: The mean age of the patients was 29.2 ± 6.8 (ranging from 18 to 36). There was a negative correlation between age and PF density (r=-0.92, %95CI: -0.99 to -0.76, p < 0.001). In-vitro AMH level of the cortical samples was significantly associated with age (R2 = 0.67, p = 0.023), primordial follicle density (R2 = 0.71, p = 0.015). There was a borderline significance between in-vitro levels of AMH and E2 level (R2 = 0.55, p = 0.058). A similar comparison could not be made for secondary follicles (preantral and small antral follicles) because of their rarity in the histological sections analyzed. CONCLUSIONS: This histomorphometric study provides evidence that in-vitro AMH production of the ovarian cortical samples reflects primordial follicle pool of the samples.

The Effect of Urine pH and Urinary Uric Acid Levels on the Development of Contrast Nephropathy.

BACKGROUND: Hyperuricemia may cause acute kidney injury by activating inflammatory, pro-oxidative and vasoconstrictive pathways. In addition, radiocontrast causes an acute uricosuria, potentially leading to crystal formation. We therefore aimed to investigate the effect of urine acidity and urine uric acid level on the development of contrast-induced nephropathy (CIN) in patients undergoing elective coronary angiography. METHODS: We enrolled 175 patients who underwent elective coronary angiography. CIN was defined as a >25% increase in the serum creatinine levels relative to basal values 48-72 h after contrast use. Prior to coronary angiography and 48-72 h later, serum uric acid, urea, creatinine, bicarbonate levels, and spot uric acid to creatinine ratio (UACR) were measured. RESULTS: Of the 175 subjects included, 29 (16.6%) developed CIN. Those who developed CIN had a higher prevalence of diabetes, higher UACR (0.60 vs. 0.44, p = 0.014), higher contrast volume, and lower serum sodium level. With univariate analysis of a logistic regression model, the risk of CIN was found to be associated with diabetes (p = 0.0016, OR = 3.8 [95% CI: 1.7-8.7]), urine UACR (p = 0.0027, OR = 9.6 [95% CI: 2.2-42.2]), serum sodium (p = 0.0079, OR = 0.8 [95% CI: 0.77-0.96]), and contrast volume (p = 0.0385, OR = 1.8 [95% CI: 1.03-3.09]). In a multiple logistic regression model with stepwise method of selection, diabetes (p = 0.0120, OR = 3.2 [95% CI: 1.3-8.1]) and UACR (p = 0.0163, OR = 6.9 [95% CI: 1.4-33.4]) were the 2 risk factors finally identified. CONCLUSIONS: We have demonstrated that higher urine UACR is associated with the development of CIN in patients undergoing elective coronary angiography.

The Positive Effects of the Human Amniotic Membrane on the Healing of Staple Line After Sleeve Gastrectomy Applied Long-Evans Rat Model.

BACKGROUND: The staple line leakage is a dangerous complication of sleeve gastrectomy. Various strategies have been tried to reduce the leakage risk. The amniotic membrane (AmM) is the inner layer of the placental membranes and has anti-inflammatory, anti-fibrosis, and anti-scarring effects, and it also has lower immune characteristics which are another essential characteristic of AmM concerning its utility for grafting. In this study, we aimed to investigate the impact of AmM on the staple line healing process of sleeve gastrectomy model in rats. MATERIALS AND METHODS: We used twenty-eight Long-Evans rats in this study. Sleeve gastrectomy was performed with tristapler. Fourteen rats served as controls, AmM was applied staple line of the other fourteen. Fourteen animals were sacrificed (seven from the AmM applied group and the other seven from the control group) on the third postoperative day. And, the other fourteen animals were sacrificed (seven from the AmM applied group and seven from the control group) on the seventh postoperative day. The tissue around the staple line was evaluated microscopically and macroscopically, bursting pressures and hydroxyproline levels were also measured. RESULTS: The bursting pressure and hydroxyproline measurements of the AmM applied group was significantly higher on the seventh postoperative day (p = 0.015, p = 0.012) Fibroblast activity and neoangiogenesis of the AmM applied group was also significantly higher on the seventh postoperative day (p = 0.004, p = 0.002). CONCLUSION: This study showed that covering of staple line of sleeve gastrectomy model in rats significantly provided higher bursting pressures and increased hydroxyproline levels, fibroblast activity, and neoangiogenesis which may potentially lead a better staple line healing. We think further investigations are needed on this issue.

Effect of nasal antihistamine on secretory IgA in nasal lavage of rats.

The humoral IgA is an immunoglobulin which plays a defensive role for organisms on mucosal surfaces. Today, intranasal antihistamines are effectively used in the treatment of allergic rhinitis. In our study, the effect of azelastine hydrochloride-a nasal antihistaminic-on humoral IgA of the nasal mucosa has been reviewed empirically. Twenty-four female Sprague-Dawley rats were included in our study. The rats were divided into three groups randomly. Group 1(azelastine hydrochloride): rats in this group had nasal azelastine hydrochloride (0.05%) applied for 30 days at 10 µl/nostril dosage. Group 2 (saline): saline (0.09%) was applied to the rats in this group for 30 days at 10 µl/nostril dosage. Group 3 (control): no application was made throughout the study. The chemicals applied in Groups 1 and 2 were applied to both nostrils by mounting a flexible micropipette to the end of an insulin injector. At the beginning of the study, nasal lavage was performed to both nostrils of the rats in every group on the 15th and 30th day to aspirate irrigation solution (distilled water). The aspirated liquids were kept at - 80° temperature and reviewed together at the end of study. Within-group comparisons: in Group 1 (azelastine hydrochloride), the humoral IgA value on the 15th day was significantly higher than the basal value (p = 0.037). There is a significant difference between humoral IgA value on the 30th day and humoral IgA value on the 15th day (p = 0.045). In Group 2 (saline), no significant difference is available between basal, 15th day and 30th day humoral IgA values (p = 0.265). In Group 3 (control), no significant difference is available between basal, 15th day and 30th day humoral IgA values (p = 0.374). Between-group comparison: there is no significant difference in between-group humoral IgA basal values (p = 0.714). On days 15 and 30, Humoral IgA value of Group 1 was significantly higher than that of Groups 2 and 3 (p = 0.013, p = 0.024, respectively). According to the results we achieved in our study, nasal antihistaminic (azelastine hydrochloride) significantly increases the level of humoral IgA. Our study is the first one in the literature to reveal a relation between nasal antihistaminic and humoral IgA and there is a further need for clinical, randomized and prospective studies.

Predicting Value of Serum Procalcitonin, C-Reactive Protein, Drain Fluid Culture, Drain Fluid Interleukin-6, and Tumor Necrosis Factor-α Levels in Anastomotic Leakage after Rectal Resection.

BACKGROUND: Anastomotic leak is the most dreaded septic complication of colorectal surgical procedures. Death is proportional to the time between occurrence and diagnosis of the leakage. Biomarkers, which may help to predict anastomotic leakage before appearance of its clinical features, may be beneficial in preventing adverse outcomes. This study investigates a biomarker that might be useful to predict rectal anastomotic leakage before its clinical presentation. PATIENTS AND METHODS: Serum procalcitonin and C-reactive protein (CRP) levels, bacterial proliferation, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels of drain fluid were evaluated in 50 consecutive patients who underwent low anterior resection without diverting ostomy for rectal carcinoma. RESULTS: Anastomotic leakage occurred in seven of 50 (14%) patients. Serum CRP and procalcitonin levels at post-operative day three were higher in patients with anastomotic leakage (p = 0.01, p = 0.02 respectively). Drain TNF-α values were increased 63.2% on post-operative day five when compared with post-operative day three in patients with anastomotic leakage, but were decreased in patients without leakage. There was no statistical difference for drain IL-6 levels between groups. The bacterial proliferation rate of drain fluid culture in the leakage group was 42.9% at post-operative day three and 85.7% at post-operative day five (p = 0.29 and p = 0.0001, respectively). CONCLUSIONS: High serum CRP and procalcitonin values on post-operative day three are alarming, and assessment of anastomotic leakage by abdominal imaging with rectal contrast is suggested. In addition, increasing levels of TNF-α and bacterial proliferation in drain fluid are predictive, whereas IL-6 is not.

Effect of Nasal Corticosteroid on Secretory Immunoglobulin A Measured in Rat Nasal Lavage: Experimental Study.

OBJECTIVE: In this study, we aimed to experimentally investigate the effects of nasal corticosteroids on the levels of secretory immunoglobulin A (sIgA) in nasal mucosa in rats. STUDY DESIGN: Prospective, randomized control trial. SETTING: Research laboratory. SUBJECT AND METHODS: Twenty-four male Sprague Dawley rats were included in our study. The rats were randomized into 3 groups. In group 1, nasal mometasone furoate was applied to the rats for 30 days. Saline was applied to group 2 for 30 days. Group 3 was the control group and received no treatment throughout the study period. Nasal lavage was conducted on both nasal openings of all rats in the 3 groups at the beginning of the study and on days 15 and 30, and the lavage solution (distilled water) was collected by aspiration. RESULTS: In group 1, the sIgA value was significantly higher at day 15 than at baseline. No significant difference was found between the sIgA values on day 15 and day 30. In groups 2 and 3, there were no significant differences in sIgA values at baseline, day 15, and day 30. The sIgA value of group 1 on day 15 was significantly higher than the values of groups 2 and 3. The sIgA value of group 1 on day 30 was significantly higher than the values of groups 2 and 3. CONCLUSION: Topical corticosteroids (mometasone furoate) applied to the nasal mucosa significantly increase nasal sIgA levels.