How Does Platelet-Rich Plasma Injection in Ovaries of Poor Responders Affect the Retrieved Oocytes, and Anti Mullerian Hormone: A Clinical Trial.

Objective: Platelet Rich Plasma (PRP) is proposed to have important role in cell division and proliferation, angiogenesis and health. This study evaluates the effect of a single injection of autologous PRP on ovarian response markers in women with poor ovarian response (POR). Materials and methods: This non-randomized clinical trial was conducted between August 2020 and September 2021. Fifty six women with Bologna criteria for POR willingly chose to participate in one of the following groups: PRP for one cycle in the time of oocyte pickup (OPU) (intervention group, n= 34) or control group (n=22).The primary outcomes were: number and quality of oocytes in coming 2 cycles of ICSI, and Anti Mullerian Hormone (AMH) level two months after PRP injection. The secondary outcomes were the number and quality of embryos and chemical pregnancy rate after embryo transfer. Results: A total of 45 participants continued the study, of which 23 were in the intervention group and 22 in control group. There were no demographic differences between two groups. At a two cycle follow up, PRP group experienced a significant improvement in AMH level and there was no respective change in control group. In one year follow up the overall pregnancy rates were same in both groups (3% Vs. 0, p=.60), while there was no difference in cumulative number and quality of embryos. Conclusion: PRP injection can improve ovarian reserve marker without adverse effects. Further evidence is required to evaluate the impact of PRP on assisted reproduction outcomes.

Effects of Cold Plasma on Staphylococcus Aureus.

Objective: To investigate the effect of cold plasma on Staphylococcus aureus destruction at different treatment times. Materials and methods: Staphylococcus aureus was cultured on 4 plates of LB Agar medium each at 1.5 × 103 CFU / mL (colony-forming unit per milliliter) and one group was selected as the control group and the other 3 groups were treated with plasma for 5, 7 and 10 minutes. They were incubated for 24 hours at 37 °C. Finally, the number of colonies formed was counted. Results: It was shown that treatment with cold atmospheric plasma significantly reduced bacterial colonies and in comparison to the control plate with a colony count of 1.5 × 103 CFU/mL treatment with air plasma for 10 minutes decreased the Pseudomonas colony count to zero. Conclusion: It was observed that the cold atmospheric plasma jet device manufactured in atomic Energy Organization of Iran can significantly kill bacteria in a short time. Increasing the duration of treatment significantly reduces bacterial colonies.

Treatment with Granulocyte-colony Stimulating Factor (G-CSF) is not associated with Increased Risk of Brain Metastasis in Patients with De Novo Stage IV Breast Cancer.

Background: Survival outcome after developing brain metastasis is poor and there is an unmet need to identify factors that can promote brain metastasis. Granulocyte-colony stimulating factor (G-CSF) is given to support neutrophil recovery after myelosuppressive chemotherapy to some patients. However, there is emerging evidence that neutrophils can promote metastasis, including through the formation of neutrophil extracellular traps (NETs), scaffolds of chromatin with enzymes expelled from neutrophils to the extracellular space. In animal models, G-CSFs can induce NETs to promote liver and lung metastasis. The primary objective of this study was to test the association between G-CSF use and the later incidence of brain metastasis. Methods: Patients with de novo Stage IV breast cancer, without known brain metastasis at the time of initial diagnosis, were identified from electronic medical records covering the period from 1/1/2013 to 12/31/2020 at Northwell Health. Univariate and multivariate logistic regression models were used to test the association between variables of interest, including G-CSF use, and brain metastasis. Results: A total of 78 patients were included in the final analysis. Among those 78 patients, 24 patients (30.8%) had received G-CSF along with chemotherapy at least once. In logistic regression models, G-CSF use was not a significant factor to predict brain metastasis (OR 1.89 [95%CI 1.89-5.33]; P=0.23). Interestingly, in multivariate logistic models, pulmonary embolism (PE)/deep venous thrombosis (DVT) was a significant predictive factor of brain metastasis (OR 6.74 [95%CI 1.82-25.01]; P=0.004) (38.5% vs 21.5%). Conclusions: The use of G-CSF was not associated with increased risk of brain metastasis in patients with de novo Stage IV breast cancer. Interestingly, PE/DVT, which can be associated with elevated NETs, was associated with brain metastasis. Further studies are warranted to determine whether DVT/PE with or without elevated NETs levels in the blood, is predictive of developing brain metastasis in patients with de novo Stage IV breast cancer.

INI-1 (SMARCB1)-Deficient Undifferentiated Sinonasal Carcinoma: Novel Paradigm of Molecular Testing in the Diagnosis and Management of Sinonasal Malignancies.

Sinonasal tumors consist of a group of rare heterogeneous malignancies, accounting for 3%-5% of all head and neck cancers. Although squamous cell carcinomas make up a significant portion of cancers arising in the sinonasal tract, there are a variety of aggressive tumor types that can present with a poorly differentiated morphology and continue to pose diagnostic challenges. Accurate classification of these unique malignancies has treatment implications for patients. Recent discoveries have allowed more detailed molecular characterization of subsets of these tumor types, and may lead to individualized treatments. INI-1 (SMARCB1)-deficient sinonasal carcinoma is a recently identified subtype of sinonasal malignancy, which is characterized by deletion of the INI-1 tumor suppressor gene. Loss of INI-1 expression has emerged as an important diagnostic feature in several human malignancies including a subset of sinonasal carcinomas. In this article, we present a case of INI-1 (SMARCB1)-deficient sinonasal carcinoma, provide an overview of recent advances in histological and molecular classification of sinonasal malignancies, and discuss challenges of caring for patients with these rare malignancies, as well as potential treatment implications. KEY POINTS: Clinicians and pathologists should recognize that a variety of sinonasal tumors can present with a poorly differentiated morphology that warrants further workup and molecular classification. Routine workup of poorly or undifferentiated sinonasal tumors should include testing for INI-1/SMARCB1, SMARCA4, and NUT. Patients with these molecularly defined subsets of tumors may benefit from clinical trials that seek to exploit these molecular alterations. The EZH2 inhibitor, tazemetostat, has demonstrated some antitumor activity in INI-1-deficient tumors, and is currently under investigation.

Natural history and clinical outcomes in patients with portal vein thrombosis by etiology: A retrospective cohort study.

BACKGROUND: Portal vein thrombosis (PVT) is an unusual-site thrombosis commonly encountered in patients with malignancies, cirrhosis, and acute abdominal inflammatory conditions (AIC). Current recommendations suggest that anticoagulation may improve recanalization rates but there is limited information on venous thromboembolism (VTE) recurrence rates and whether the etiologies of PVT respond similarly with anticoagulation. OBJECTIVE: To characterize the natural clinical course and outcomes of patients diagnosed with PVT based on etiology. PATIENTS/METHODS: Patients with a diagnosis of PVT between 2005 and 2015 who were followed for at least one year and had revised imaging at 12 months ±â€¯3 months were identified. Comorbidities, demographics, anticoagulation choice and clinical outcomes including VTE recurrence, cavernous transformation, PVT recanalization, progression and mortality were obtained. RESULTS: Of 698 patients diagnosed with PVT, 85 patients were evaluable according to criteria: 54 had cirrhosis (63.5%), 15 malignancy (17.6%) and 16 AIC (18.8%). Mean age was 55.6 ±â€¯13.1 years. At presentation, 40% patients were symptomatic and 29.4% received anticoagulation. Patients with AIC were anticoagulated more frequently compared to those with malignancy or cirrhosis (87.5% vs. 33.3% vs. 11.1%). Overall, patients with cirrhosis had lower rates of PVT progression (0% vs. 13.3%, p = 0.02) and patients with AIC had higher rates of cavernous transformation compared to cirrhosis or malignancy-associated PVT (31.3% vs. 7.4% vs. 0%, p = 002). Among untreated patients, those with malignancy had significantly higher rates of VTE recurrence and PVT progression than patients with cirrhosis (20% vs. 4.2% and 20% vs. 0%). CONCLUSIONS: The natural course of PVT differs among etiologies. In the absence of anticoagulation, patients with malignancy are more prone to VTE recurrence and PVT progression compared to patients with cirrhosis. Given the high rate of VTE recurrence at 12 months in patients with malignancy-associated PVT, anticoagulation should be considered for this group.

A Rare Case of Gemcitabine-Induced Pulmonary Hypertension.

CONTEXT: Gemcitabine is the backbone of systemic treatment of locally advanced and metastatic intrahepatic cholangiocarcinoma. In recent literature, gemcitabine has been linked to various pulmonary side effects. CASE REPORT: We report a case of an 82-year-old male who developed acute pulmonary hypertension after receiving one cycle of gemcitabine for metastatic cholangiocarcinoma. His symptoms began with fatigue associated with shortness of breath and cough that worsened despite dose reduction. He developed new onset bilateral pulmonary effusions and an echocardiogram revealed findings consistent with pulmonary hypertension. A computed tomography (CT) angiogram was negative for pulmonary thromboembolism. Although he was promptly treated with diuretics and steroids, the patient could not tolerate any further therapy. CONCLUSION: Gemcitabine-induced pulmonary hypertension is rare and can be challenging to diagnose, as it remains a diagnosis of exclusion. However, physicians should be vigilant of new pulmonary symptoms, as delayed treatment can cause significant patient morbidity and mortality.

Prevalence of anaphylaxis among adults admitted to critical care for severe asthma exacerbation.

BACKGROUND: In asthmatics, making a diagnosis of anaphylaxis could be challenging as respiratory symptoms are a common feature of both conditions. Identifying anaphylaxis is important to providing appropriate care. A prior study showed that anaphylaxis is sometimes misdiagnosed as acute asthma in children. We sought to identify the percentage of adults admitted to the intensive care unit (ICU) with asthma exacerbations who met criteria for anaphylaxis. METHODS: Retrospective chart review of adults admitted with acute asthma to the ICU at Jacobi Medical Center, a Level 1 trauma centre in Bronx, New York. Study period was January 2012 to December 2014. Using the criteria outlined in the World Allergy Organization's Anaphylaxis Guidelines, we identified patients who met criteria for anaphylaxis. RESULTS: 105 patients were identified: 17 were excluded because their main reason(s) for admission was not asthma. 7 (8%) of the 88 cases eligible for the study met diagnostic criteria for anaphylaxis while 3 (3.4%) were highly likely to have had anaphylaxis. The baseline characteristics of the seven patients were similar to that of the overall population studied. They however had shorter onset of symptoms (median (IQR): 3.5 (2-6) vs 24 hours (12-72), p<0.001), were more likely to have been intubated (71%vs31%, p=0.04), received intramuscular epinephrine by the emergency medical services or in the emergency room (86%vs42%, p=0.04) and received antihistamines (28.6%vs1.2%, p=0.02). None of these seven patients died. Only one of the seven patients was prescribed an epinephrine pen injector and referred to an allergist at discharge. CONCLUSION: In this single-centre retrospective review, 3.4% of adults admitted to the ICU for acute severe asthma also met criteria for anaphylaxis.

A Randomized Trial to Evaluate the Effect of Local Endometrial Injury on the Clinical Pregnancy Rate of Frozen Embryo Transfer Cycles in Patients With Repeated Implantation Failure.

Objective: Repeated implantation failure (RIF) is a condition in which the embryos implantation decreases in the endometrium. So, our aim was to evaluate the effect of local endometrial injury on embryo transfer results. Materials and methods: In this simple randomized clinical trial (RCT), a total of 120 patients were selected. The participants were less than 40 years old, and they are in their minimum two cycles of vitro fertilization (IVF). Patients were divided randomly into two groups of LEI (Local endometrial injury) and a control group (n = 60 in each group). The first group had four small endometrial injuries from anterior, posterior, and lateral uterus walls which were obtained from people who were in 21th day of their previous IVF cycle. The second group was the patients who have not received any intervention. Results: The experimental and control patients were matched in the following factors. Regarding the clinical pregnancy rate, there was no significant difference noted between the experimental and the control group. Conclusion: Local endometrial injury in a preceding cycle does not increase the clinical pregnancy rate in the subsequent FET cycle of patients with repeated implantation failure.

Zygote intrafallopian tube transfer versus intrauterine cleavage or blastocyst stage transfer after intracytoplasmic sperm injection cycles in patients with repeated implantation failure: A prospective follow-up study.

AIM: This study aimed to compare the outcomes between zygote intrafallopian transfer (ZIFT) with intrauterine day-3 (cleavage stage) embryo transfer and intrauterine day-5 (blastocyst stage) embryo transfer in patients undergoing intracytoplasmic sperm injection. MATERIAL AND METHODS: This prospective study was performed at Royan Institute, Tehran, Iran, between January 2012 and January 2014. Two hundred fifty women with more than three unexplained implantation failures were divided non-randomly into three groups according to embryonic age and methods used as follows: (i) intrauterine cleavage-stage embryo transfer (n = 100); (ii) intrauterine blastocyst-stage embryo transfer (n = 50); and (iii) ZIFT (n = 100). Implantation, clinical pregnancy, miscarriage and live birth rates were our main outcomes. RESULTS: Patients' characteristics and ovarian response were comparable among the three groups. Implantation rate (56.1% vs 27.9%) was significantly higher in the blastocyst group as compared to the ZIFT group; however, clinical pregnancy rate (38% vs 23%) was not statistically significantly different between the two groups, but due to the significantly higher miscarriage rate (34.7% vs 5.3%) in the ZIFT group, the live birth rate was significantly higher in the blastocyst group (P = 0.04). No significant differences were found between the cleavage-stage and blastocyst-stage groups in terms of implantation, clinical pregnancy, miscarriage and live birth rates. CONCLUSION: We do not recommend the use of the ZIFT procedure for patients with repeated implantation failures. It seems that replication of cleavage- or blastocyst-stage embryo transfer is more efficient and affordable.

Artificial Endometrial Preparation for Frozen-Thawed Embryo Transfer with or without Pretreatment with Depot Gonadotropin Releasing Hormone Agonist in Women with Regular Menses.

OBJECTIVE: To investigate the reproductive outcome of artificial endometrial preparation with exogenous steroids for frozen-thawed embryo transfer with and without pre-treatment with depot gonadotropin releasing hormone agonist (GnRH-a) in women with regular menses. MATERIALS AND METHODS: This is a prospective randomized clinical trial conducted in two ART centers on 176 women undergoing frozen-thawed embryo transfer. All patients received oral estradiol valerate 4 mg daily from day 2 to day 5 and 6 mg per day from day 6 to the day of the pregnancy test. In day 13 of cycle, an ultrasound examination was performed. After ultrasound confirmation of endometrial thickness (≥8 mm) and no ovarian activity, progesterone in cyclogest supp (800 mg daily) was added. The dose of estradiol would be increased to 8 mg per day if the endometrial thickness was less than 8mm. Two or 3 embryos were transferred via transcervical route 48 hours after the beginning of progesterone administration. In group A (93 patients), Difereline (3.75 mg Im), as a depot GnRH agonist was administered in the midluteal phase (day 21) of previous cycle. In the other group B (n = 83) steroid supplementation was commenced without prior pituitary suppression. Chemical and clinical pregnancy rates were compared in two groups. RESULTS: No significant differences were seen between two groups in terms of chemical pregnancy and clinical pregnancy rates. CONCLUSION: The findings support the artificial protocol without any pretreatment suppressive drugs to reduce the adverse side effects of GnRH agonists also to minimize the costs.

Prominent complaint: a guide to medical therapy of overactive bladder syndrome in older women.

To evaluate Overactive bladder (OAB) with detrusor overactivity (DOA) following oxybutynin or tolterodine treatment in recommended doses at a four-week course. A total of 100 Iranian women 45 years or older with urgency that also showed idiopathic detrusor overactivity (IDO) in the filling phase of their cystometry were included in the current study. In this double-blinded trial two parallel groups were randomized by using two kinds of the antimuscarinic drugs for a four- week course [oxybutinin 5mg, t.d.s. or Tolterodin 2mg, b.i.d.] in the same  packages. Data were collected from three-day frequency volume chart (FVC) one month before and after the treatment course. The effectiveness of each drug was compared using the paired, samples t-test. Patients' improvement regarding urinary urgency, frequency and urge incontinence after treatment in both groups was seen, but mean improvements in the terms of urgency and urge incontinence were larger in patients who were treated by oxybutynin. Night-time frequency was shown to be improved by a significantly larger score by tolterodine. Discontinuation of treatment due to adverse events had no significant difference in two groups. Four-week treatment with oxybutynin was better than tolterodine IR in improving urgency and urge incontinence, but there were not statistically significant difference between them. In planning a course of treatment especially in the elderly, the difference in the group of symptoms that reduce patients' quality of life should be considered. Physicians should consider the patient's prominent symptom in selection of anti-muscarinic drugs for the treatment of overactive bladder syndrome especially in elderly patients.

Effects of ethinyl estradiol plus desogestrel on premenstrual symptoms in Iranian women.

Marvelon®, a combined oral contraceptive, contains 30 µg ethinyl estradiol (EE) and 150 µg desogestrel (DE), and has been shown to be a well-tolerated and effective combination that provides high contraceptive reliability and good cycle control. However, its efficacy has not been yet evaluated among Iranian women. Thus, the study aimed to determine the effect of oral contraceptive pill on treating premenstrual symptoms and on various parameters associated with well-being and health in a sample of Iranian. This clinical trial (before- after) study was performed at the family-planning clinic of the centers under the supervision of Tehran University of Medical Sciences on sixty-one women. The study protocol was approved by the Ethics Committee of Tehran University of Medical Sciences and all participants received a 21/7-day regimen of oral contraceptive containing 150 µg desogestrel (DE) and 30 µg ethinyl estradiol (EE) for six cycles. Efficacy parameters included changes in premenstrual symptoms were also assessed. Clinical data was collected by calendar of premenstrual experiences (COPE) at baseline and treatment cycles 1,2, 3 and 6. Clinical variables were measured including low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels for two timing periods (baseline and last visit). Linear mixed model analyses were used to analyze differences in changes of the four factors of premenstrual syndrome (PMS), weight and blood pressure during these timing periods. The mean age of the women was 28.52 (SD=6.75) years. Participants on average had been pregnant 1.13 (SD=1.16) times. The linear mixed model analyses indicated that premenstrual syndrome symptoms reduced significantly over time (P<0.05). Marvelon® showed no significant effect on reducing LDL and HDL levels, and participant's weights were also stable during five-time assessments (P>0.05). A combined oral contraceptive containing ethinyl estradiol and desogestrel has a positive effect on women's health and reduces premenstrual symptoms.

Psychometric properties of the Iranian version of the female sexual distress scale-revised in women.

INTRODUCTION: Several tools for the assessment of sexuality-related distress are now available. The Female Sexual Distress Scale (FSDS) and its revised version (FSDS-R) are extensively validated and among the most widely used tools to measure sexually related personal distress. AIM: The aim of the study was to determine the psychometric properties of the Iranian version of the FSDS-R in a population sample of Iranian women. METHODS: A total of 2,400 married and potentially sexually active women were recruited and categorized into three groups including (i) a healthy control group; (ii) a group of women with hypoactive sexual desire disorder (HSDD); and (iii) a group of women suffering from other female sexual dysfunction (FSD). Participants were asked to complete a set of questionnaires including the Iranian version of the Female Sexual Function Index (FSFI-IV), the FSDS-R, and the Hospital Anxiety and Depression Scale. MAIN OUTCOME MEASURES: Sexuality-related distress and FSD as assessed by the Iranian version of the FSDS-R and the FSFI-IV are the main outcome measures. RESULTS: Internal consistencies and test-retest reliability of the FSDS-R across the three assessments points for the three groups were >0.70. The FSDS-R correlated significantly with anxiety, depression, and the FSFI total score. Significant differences in the FSDS-R scores were found between healthy women, women with HSDD, and women with other types of FSD. Factor analysis of the FSDS-R yielded a single-factor model with an acceptable fit. CONCLUSIONS: The Persian version of the FSDS-R is a valid and reliable instrument for the assessment of sexuality-related distress in Iranian women and can be used to screen patients with HSDD.

GnRH antagonist versus agonist in normoresponders undergoing ICSI: a randomized clinical trial in Iran.

BACKGROUND: General concern is that the pregnancy rate is higher with GnRH-agonist as a protocol of pituitary suppression. GnRH-antagonist protocol provides a shorter period of administration and an easy flexible protocol. OBJECTIVE: In this study, the outcomes of GnRH agonist and antagonist in ICSI cycles are compared in normo responder patients. MATERIALS AND METHODS: In this randomized clinical trial, 300 normoresponders undergoing ICSI were randomly divided to GnRh agonist (n=150) and GnRh antagonist (n=150) groups. The main outcome measurements were chemical, clinical and ongoing pregnancy rates (PR). RESULTS: The mean duration of stimulation were 9.6±1.6 and 8.2±1.6 days in agonist and antagonist groups respectively (p=0.001). The mean number of MII oocyte retrieved in agonist and antagonist groups were 7.7±4.0 and 6.9±4.3 respectively (p=0.03). There was no significant difference between two groups regarding mean number of gonadotrophin ampoules, follicles, occytes, total embryos and good quality embryos, OHSS incidence, and abortion rate. Chemical pregnancy rate was 35.3% in agonist and 39.3% in antagonist group. Clinical pregnancy rate was 35.3% in agonist and 34% in antagonist group. Ongoing pregnancy rate was 45 (31.3%) in agonist and 44 (29.3%) in antagonist group. There was no significant difference between two groups in pregnancy rates. CONCLUSION: In this study antagonist protocol was shown to be an easy, safe and friendly protocol in Iranian normoresponder patients, having similar outcomes with standard agonist protocol but shorter period of stimulation.

Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphen citrate gonadotropins in controlled ovarian hyperstimulation: a prospective, simply randomized, clinical trial.

OBJECTIVE: To study the efficacy of the aromatase inhibitor letrozole in controlled ovarian hyperstimulation (COH). MATERIAL AND METHODS: In this prospective simply randomized clinical trial, one hundred forty patients with unexplained infertility undergoing intrauterine insemination (IUI) therapy were randomized to receive either letrozole or clomiphene citrate (CC)-gonadotropin. The patients were selected among patients referred to one university hospital and one private infertility clinic. A letrozole dose of 5 mg/day (n = 70) was given on days 3-7 of the menstrual cycles. Clomiphen citrate a dose of 100 mg/day was given like letrozole but combined with human menopausal gonadotropin (hMG) dose of 75 IU/ml administered every day starting on day 6. Ovulation was triggered with urinary hCG (10,000 IU) when the leading follicle(s) reached 18 mm in diameter. A single IUI was performed 36 hours later. The luteal phase was supplemented with micronized progesterone vaginally. Ovarian stimulation response (E2 levels and number of follicles) was primary outcome. RESULTS: There were no differences in demographic characteristics between groups. The number of mature follicles (1.8 +/- 0.7 vs. 2.46 +/- 2.3; P = 0.042) and serum E2 level on the day of hCG (310 +/- 135.4 vs. 1,670.7 +/- 1021.8 pg/ml, respectively; P < 0.0001) were significantly lower in letrozole group. A significantly higher endometrial thickness was observed at the time of hCG administration in patients that received letrozole (9.7 +/- 1.6 mm vs. 7.8 +/- 2 mm; P < 0.001). Clinical pregnancy rates also were significantly higher in letrozole group (32.8% vs. 14.3%, respectively; P < 0.01). CONCLUSION: The aromatase inhibitor letrozole appears to constitute a good alternative to CC-gonadotropin in patients with unexplained infertility undergoing COH cycles combined with IUI therapy.