Immunotherapy: SYNERGISTIC PERITONEAL ANTI-TUMOR EFFECT OF ALLOCETRAOTS, A CELLULAR IMMUNE-THERAPY, IN COMBINATION WITH IMMUNE CHECKPOINT INHIBITORS/CHEMOTHERAPY, THROUGH IN-VIVO REPROGRAMMING OF MACROPHAGES AND DENDRITIC CELLS

Background & Aim: Immune checkpoint inhibitors (ICI) revolutionized solid tumor treatment, however, in many tumors only partial response is achieved. Allocetra-OTS has an immune modulating effect on macrophages and dendritic cells and showed an excellent safety profile in patients including patients with sepsis and Covid-19. Here we investigated the anti-tumoral effect of Allocetra-OTS cellular therapy, in peritoneal solid tumor animal models. Methods, Results & Conclusion(s): Allocetra-OTS is manufactured from enriched mononuclear fractions and induced to undergo early apoptosis. Balb/c mice were inoculated intraperitoneally (IP) with AB12 (mesothelioma) with pLenti-PGK-V5-Luc-Neo and treated with anti- CTLA4 with or without Allocetra-OTS. Mice were monitored daily for clinical score and weekly using IVIS (Fig.1). Kaplan-Meier log rank test was done for survival. For Allocetra-OTS preparation, enriched mononuclear fractions were collected by leukapheresis from healthy eligible human donors and induced to undergo early apoptosis. Anti- CTLA4 standalone therapy significantly improved survival (Fig.2) from mean 34+/-9 to 44.9 +/-20 days. However, OTS standalone therapy was non-inferior and improved survival to 52.3 +/-20 days. Anti-CTLA4 + Allocetra-OTS combination therapy, ameliorated survival to 86.7+/-20 days with complete cancer remission in 60-100% of mice. Similar anti- tumoral effects of Allocetra-OTS were seen in mesothelioma model in a combination therapy with either anti-PD1 or cisplatin and using anti-PD1 in ID8 ovary cancer model. Based on single cell analysis confirmed by flow cytometry and pathology, the mechanism of action seems to be related or at least associated with an increase in f/480high peritoneal macrophages and a decrease in recruited macrophages, and to f/480high infiltration of the tumor. However, further studies are needed to confirm these observations. During IP tumor progression, Allocetra-OTS as a standalone therapy or in combination with ICI, or cisplatin, significantly reduced tumor size and resulted in complete remission in up to 100% treated mice. Similar results were obtained in ID8 ovary cancer. Based on excellent safety profile in > 50 patients treated in prior clinical trials for sepsis and Covid-19, Phase I/II clinical trial of Allocetra-OTS plus chemotherapy has started and three patient already recruited. A second phase I/II clinical trial of Allocetra- OTS plus anti-PD1, as a second- and third-line therapy in various cancers, was initiated in Q1 2023. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

The relationship between inflammatory diet score and cancer-specific outcomes: Systematic review and meta-analysis

Cancer remains one of the most prevalent diseases in the United States and a leading cause of death. Large prospective studies have found significant correlations between dietary intake and cancer. Chronic inflammation promotes pro-cancer inflammatory environments and nutrition can influence inflammation, with the intake of certain food items increasing inflammatory biomarkers. The objective of this research was to explore the relationship between inflammatory diet score measured by the Dietary Inflammatory index and all-cause mortality, cancer-specific mortality, and cancer recurrence among cancer survivors. Web of Science, Medline, CINHAL, and PsycINFO databases were searched to collect potentially eligible sources that focus on dietary inflammation and cancer outcomes. All sources were uploaded to Covidence software and screened by two independent blinded reviewers. The quality of the sources was assessed using the Newcastle Ottawa scale and relevant data was extracted and transferred to the Comprehensive Meta Analysis software and a random effects model was used to perform meta-analysis. Of the 1444 studies imported into the Covidence software, 13 passed all the screening stages and were included in the final analysis. Eight studies reported on pre-diagnosis diet while five others reported on postdiagnosis diet. Five studies reported on colorectal cancer, four on breast cancer, two on ovarian cancer, one on endometrial cancer and one on prostate cancer. Meta-analysis of the studies found that being in the highest postdiagnosis DII score indicating pro-inflammatory diet significantly increased the risk of all-cause death among cancer survivors by 33.5% (HR = 1.335, 95% CI = 1.049, 1.698, n = 6). Analysis did not show a statistically significant association between DII score and cancer mortality or recurrence (HR = 1.097, 95% CI = 0.939, 1.281, n = 6). Analysis by cancer subtype found a significant correlation between postdiagnosis DII score and all-cause mortality among the breast cancer survivors (HR = 1.335, 95% CI = 1.041, 1.711, n = 3) though there were no significant associations between DII and the outcomes of interest from the other cancer types. The meta-analysis concludes that being in the highest postdiagnosis DII score group significantly increased the risk of all-cause death among cancer survivors. This suggests that risk of all-cause mortality could be reduced for cancer survivors by consuming more anti-inflammatory food components and reducing consumption of pro-inflammatory foods. These findings also warrant more research in this field to clarify the relationship between dietary inflammation as measured by the DII and cancer outcomes, particularly cancer-specific mortality.

Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

Impact of COVID-19 Restriction on Weight, Physical Activity, Diet and Psychological Distress on People with PCOS.

BACKGROUND: People with polycystic ovary syndrome (PCOS) have higher weight gain and psychological distress compared to those without PCOS. While COVID-19 restrictions led to population level adverse changes in lifestyle, weight gain and psychological distress, their impact on people with PCOS is unclear. The aim of this study was to investigate the impact the 2020 COVID-19 restrictions had on weight, physical activity, diet and psychological distress for Australians with PCOS. METHODS: Australian reproductive-aged women participated in an online survey with assessment of weight, physical activity, diet and psychological distress. Multivariable logistic and linear regression were used to examine associations between PCOS and residential location with health outcomes. RESULTS: On adjusted analysis, those with PCOS gained more weight (2.9%; 95% CI; 0.027-3.020; p = 0.046), were less likely to meet physical activity recommendations (OR 0.50; 95% CI; 0.32-0.79; p = 0.003) and had higher sugar-sweetened beverage intake (OR 1.74; 95% CI 1.10-2.75; p = 0.019) but no differences in psychological distress compared to women without PCOS. CONCLUSIONS: People with PCOS were more adversely affected by COVID-19 restrictions, which may worsen their clinical features and disease burden. Additional health care support may be necessary to assist people with PCOS to meet dietary and physical activity recommendations.

Long-Term Efficacy and Safety of Upadacitinib in Patients with Psoriatic Arthritis Refractory to Biologic Therapies: 2-Year Results from the Phase 3 Select-Psa 2 Study

Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to >=1 biologic disease modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECTPsA 2. Methods Pts were randomized to UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatmentemergent adverse events (TEAEs) were summarized for pts who received >=1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received >=1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to>=1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension.

Refractory epilepsia partialis continua during SARS-CoV-2 infection

We report about an 87-year-old female patient who had an ovarian tumor 2 years ago. Further on she developed an epilepsia partialis continua (Kojewnikoff epilepsy) concomitant with a paraneoplastic syndrome with positive anti-Yo detection in the CSF during a SARS-CoV-2 infection.Copyright © 2023 Georg Thieme Verlag. All rights reserved.

Plausible Impacts of SARS-CoV-2 on Human Reproductive System

SARS-CoV-2, a member of the family Coronaviridae, is a positive-stranded RNA virus with the spike glycoproteins present on its envelope. ACE2 serves as the entry mediator of SARS-CoV-2 as it attacks mainly the organs of the respiratory, cardiovascular, digestive, and urinary system showing high expression of ACE2 or TMPRSS2. ACE2 is found to have significant differential expression in all the reproductive tissues, thus posing the reproductive system vulnerable to the adverse effects of SARS-CoV-2 infection. Previous coronavirus attacks (SARSCoV and MERS) have also been known to impose adverse effects on the reproductive system. Therefore, there is a dire need to safeguard the reproductive system against COVID-19 as it not only bothers the present generation but may also affect the well-being of future progeny. Since the inception of pandemic, several scientific studies have been carried out to assess its impact;yet there are research lacunas to claim reproductive system as a potential target of this deadly virus. To avoid the detrimental effects of the current pandemic on reproductive sustainability, well-planned large-scale and multicentric cohort follow-up studies are mandatory for accurate evaluation of the enduring effects of SARS-CoV-2 infection on human fertility and pregnancy outcomes. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Analysis of Cardiovascular Complications during Delivery Admissions Associated with COVID-19

BACKGROUND: Persons with Coronavirus Disease 2019 (COVID-19) infection have an increased risk of pregnancy-related complications. However, data on acute cardiovascular complications during delivery admissions remain limited. OBJECTIVE(S): To determine whether birthing individuals with COVID-19 have an increased risk of acute peripartum cardiovascular complications during their delivery admission. METHOD(S): This population-based retrospective cohort study used the National Inpatient Sample (2020) by utilizing ICD-10 codes to identify delivery admissions with a diagnosis of COVID-19. A multivariable logistic regression model was developed to report an adjusted odds ratio for the association between COVID-19 and acute peripartum cardiovascular complications. RESULT(S): A total of 3,458,691 weighted delivery admissions were identified, of which 1.3% were among persons with COVID-19 (n=46,375). Persons with COVID-19 were younger (median 28 vs. 29 years, p<0.01) and had a higher prevalence of gestational diabetes mellitus (GDM), preterm births and Cesarean delivery (p<0.01). After adjustment for age, race/ethnicity, comorbidities, insurance, and income, COVID-19 remained an independent predictor of peripartum cardiovascular complications including preeclampsia (aOR 1.33 [1.29-1.37]), peripartum cardiomyopathy (aOR 2.09 [1.54-2,84]), acute coronary syndrome (ACS) (aOR 12.94 [8.85-18.90]), and cardiac arrhythmias (aOR 1.55 [1.45-1.67]) compared with no COVID-19. Likewise, the risk of in-hospital mortality, AKI, stroke, pulmonary edema, and VTE was higher with COVID-19. For resource utilization, cost of hospitalization ($5,374 vs. $4,837, p<0.01) was higher for deliveries among persons with COVID-19. CONCLUSION(S): Persons with COVID-19 had a higher risk of preeclampsia, peripartum cardiomyopathy, ACS, arrhythmias, in-hospital mortality, pulmonary edema, AKI, stroke, and VTE during delivery hospitalizations. This was associated with an increased cost of hospitalization. Keywords: COVID-19, Pregnancy, GDM, PCOS, Preeclampsia, CVD, Cardiovascular Disease Abbreviations: COVID-19: Coronavirus disease-2019, GDM: Gestational Diabetes Mellitus, PCOS: Polycystic Ovary Syndrome, National Inpatient Sample: NIS, AHRQ: Agency for Healthcare Research and Quality, HCUP: the Healthcare Cost and Utilization Project Funding and Conflicts of Interest Dr. Michos reports Advisory Board participation for Amgen, AstraZeneca, Amarin, Bayer, Boehringer Ingelheim, Esperion, Novartis, Novo Nordisk, and Pfizer. The remaining authors have nothing to disclose.Copyright © 2023

Fitness Assessments of Women with Polycystic Ovary Syndrome: A Prospective Process Feasibility Study

Background: Fitness is a marker of physiological and mental health. The purpose of this pilot study was to assess the feasibility of processes to recruit women with polycystic ovary syndrome (PCOS) during the Covid pandemic and collect their health and fitness data. Additionally, the data was used to explore possible associations between anthropometrics, PCOS biomarkers, health-related quality-of-life (HRQoL), and depressive symptoms with that of fitness and self-reported physical activity levels among women with PCOS. Method(s): A convenience sample of women with PCOS (n = 15) were recruited via flyers and the snowball method. Participants completed surveys, anthropometrics, a dual energy x-ray absorptiometry scan, blood work, and a fitness assessment. Data were statistically analyzed using Spearman correlations. Result(s): Feasibility measures of recruitment and retention rates were 83% and 100%, respectively. Fidelity measurement for process averaged 97%. Participants (age 25.9 (+/- 6.2), mostly White (80%), single (60%), and employed full-time (67%)) were categorized as obese (body mass index (BMI) 32.2 kg/m2 +/- 8.3, percent bodyfat 41.1% +/- 8.1) with <=1 comorbidity. Most participants were not regularly physically active and had high free testosterone levels (7.6 pg/mL+/-4.3), elevated high-density lipoprotein (63.2 mg/dL+/-12.9), fair cardiovascular capacity, and below average muscular strength/endurance. The following statistically significant and strong associations were found: (1) VO2 max with percent bodyfat (-0.59;p = 0.02), sex hormone binding globulin (0.73;p = 0.00), HRQoL (0.72;p = 0.00), and depressive symptoms (-0.67;p = 0.00), (2) abdominal strength with BMI (-0.66;p = 0.01) and high density lipoprotein (HDL) (0.59;p = 0.02), (3) physical activity level with percent bodyfat (-0.72;p = 0.00), and (4) resistance training with low density lipoprotein (LDL) (-0.52;p = 0.05). Conclusion(s): Collecting health and fitness data from women with PCOS is a feasible research approach. Randomized controlled trials in which health and fitness data are collected from women with PCOS are needed to confirm possible associations between fitness and PCOS clinical features and is in the planning process. Copyright: Copyright © 2023 The Author(s).

A novel cystic fibrosis-pregnancy service: Two-year review after introduction of elexacaftor/tezacaftor/ivacaftor

Background: As a quality service improvement response since elexacaftor/ tezacaftor/ivacaftor (ELX/TEZ/IVA) became available and the yearly average number of cystic fibrosis (CF) pregnancies (n = 7 pre-2020, n = 33 in 2021) increased significantly at an adult CF center (~600 people with CF), a monthly multidisciplinary CF-maternal health virtual clinic was established with antenatal virtual CF exercise classes dedicated to providing adaptive, specialist support to this cohort, aswell as outreach guidance and education to local obstetric teams. Method(s): This was a single-center retrospective reviewof Royal Brompton Hospital CF-Maternal Health multidisciplinary team clinic records and a patient survey from March 2020 to March 2022. Result(s): Of 47 pregnancies in 41 women (median age 30;) eligible for ELX/ TEZ/IVA at start of pregnancy, 40% (n = 19) were unplanned, and 19% (n = 9) used assisted conception. Three women with a history of infertility conceived naturally, having required assisted conception for previous pregnancies, and five women had multiple pregnancies during the study period. ELX/TEZ/IVA was continued in 60% (n = 28), delayed in 28% (n = 13), and stopped in 13% (n = 6) of pregnancies through maternal choice and careful clinical counselling. Pre-pregnancy pulmonary status was poorer in women who continued than in those who delayed or stopped (Table 1). Of those who stopped, 85% (n = 5) restarted because of pulmonary deterioration by the third trimester. Prenatal CF complications included at least one episode of minor hemoptysis in 21% (n = 9/41) of women, at least one infective exacerbation in 55% of pregnancies (n = 26/47), and noninvasive ventilation in one woman. Other pregnancy-associated complications included one case of ovarian hyperstimulation syndrome, one case of sub-segmental pulmonary embolism, and two cases of pregnancy-induced hypertension. Excluding 10 first trimester terminations, 10 current pregnancies, and one patient relocation, obstetric outcomes available for 26 pregnancies confirmed a live birth rate of 85% (n = 22/26) and a 15% first-trimester miscarriage rate (n = 4). Obstetric complications included preterm delivery rate of 23% (n = 6/26), including two cases of COVID infection resulting in two neonatal intensive care unit admissions, one case of endometritis after cesarean section, and a fourthdegree perineal tear. There were no ectopic pregnancies, maternal or neonatal deaths, or reports of infant cataracts or congenital malformations. Median gestational age was 37/40 weeks (range 29-40). Mode of delivery was via cesarean section in 45% (n = 10/22, of which twowere emergency) and vaginal in 55% (n = 12/22), of which 83% (n = 10/12) were via induction of labor for diabetes (CF or gestational) indication. Deliveries were supported and occurred equally at local obstetric units and in tertiarycare obstetric hospital settings (50%, n = 11/22). Patient-experience survey responses cited high levels of confidence in health optimization and prioritization during pregnancy and praised excellent inter-health care provider communication and peer-to-peer emotional support provided among expectant mothers in the virtual prenatal exercise groups. Table 1. Baseline demographic and clinical characteristics of elexacaftor/tezacaftor/ivacaftoreligible expectant mothers according to therapeutic decision (Table Presented) Conclusion(s): In the absence of clinical trial safety data, the novel approach of a dedicated CF-maternal health multidisciplinary team clinic with local obstetric outreach support has ensured regular specialist clinical and emotional peer-to-peer support for this cohort of women eligible for ELX/ TEZ/IVA to ensure optimal outcomes and experiences of their pregnancies, where appropriate, close to home.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

27th Asia and Oceania Federation of Obstetrics and Gynecology Congress

The proceedings contain 358 papers. The topics discussed include: role of early prophylactic aspirin on Covid-19 outcome in antenatal patients - an audit of a hospital in India;partial intestinal obstruction complicating pregnancy: diagnostic dilemma and management;a case report of uterine rupture recognized during cesarean section at the site of a previous hysteroscopy-related perforation;menstrual characteristics and its related morbidities among adolescent girls living in North Borneo, Malaysia: a questionnaire-based study;the volume of posterior cervical varicose correlates with intraoperative blood loss in placenta previa;implications of large fibroids in pregnancy: a multidisciplinary approach;unexpected ovarian malignancy in postmenopausal women following laparoscopic surgery for adnexal masses - a review of 5 years;post radiotherapy outcome on cervical cancer stage IIIB patients with and without paraaortic lymph nodes enlargement;and evaluation of the relationship between thrombocytosis and clinico-pathological factors of patients with epithelial ovarian cancer.

Prevalence of Polycystic Ovary Syndrome amongst Females Aged between 15 and 45 Years at a Major Women's Hospital in Dubai, United Arab Emirates.

Objective criteria have been scarce in published data on the occurrence of polycystic ovary syndrome (PCOS) in the United Arab Emirates (UAE). It is crucial that we enhance our comprehension of PCOS prevalence in the UAE to inform key stakeholders about the disease's burden and enable comparisons with other nations. This research aimed to examine the PCOS prevalence at a large academic tertiary centre in Dubai, UAE, called Latifa Women and Children's Hospital. We performed a cross-sectional study by reviewing the electronic medical records of patients accessing care between 2017 and 2022 (5 years). By utilizing the international classification of diseases codes (ICD-10), we discovered a period prevalence of PCOS of 1.6% among 64,722 women aged between 15 and 45 years. It is worth noting that the estimated annual point prevalence rose from 1.19% in 2020 (at the beginning of the COVID19 pandemic) to 2.72% in 2022 (after the start of the COVID-19 pandemic). Therefore, the odds ratio of the risk of a PCOS diagnosis in 2022 compared to 2020 was 2.28. The majority of the women diagnosed with PCOS in this study had an ICD-10 code of E28.2. Women with PCOS were younger than the controls, less likely to be pregnant, and had a higher body mass index and systolic and diastolic blood pressure. This is the most extensive research to date examining PCOS prevalence in the UAE, and it emphasizes the significance of this condition. It is crucial to prioritize PCOS to prevent morbidity and mortality from reproductive and long-term health consequences, including infertility, type 2 diabetes and endometrial cancer, which is presently the most frequent gynecological cancer in the UAE.

A therapeutic chimeric IgG/IgA expressed by CHO cells for oral treatment of PED in piglets.

Immunoglobulin A (IgA) of sows is critically important for assessing piglets' protective capacity against porcine epidemic diarrhea virus (PEDV). Here, we report a therapeutic chimeric anti-PEDV IgG/IgA expressed by Chinese hamster ovary (CHO) cells for oral treatment of PED. The chimeric anti-PEDV IgG/IgA was produced by the CHO cell lines, in which the heavy chain was constructed by combining the VH, Cγ1 and hinge regions of PEDV IgG mAb 8A3, and the Cα2 and Cα3 domains of a Mus musculus immunoglobulin alpha chain. The chimeric anti-PEDV IgG/IgA could neutralize the strains of CV777 (G1), P014 (G2) and HN1303 (G2) in vitro effectively, showing broad-spectrum neutralization activity. The in vivo challenge experiments demonstrated that chimeric anti-PEDV IgG/IgA (9C4) produced in the CHO cell supernatant could alleviate clinical diarrhea symptoms of the PEDV infection in piglets. In general, our study showed that chimeric anti-PEDV IgG/IgA produced from CHO cell line supernatants effectively alleviates PEDV infection in piglets, which also gives the foundation for the construction of fully functional secretory IgA by the J chain introduction to maximize the antibody therapeutic effect.

An update of polycystic ovary syndrome: causes and therapeutics options.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by menstrual irregularities, chronic anovulation, hirsutism, androgenic alopecia, and acne. At diagnosis, patients can with different manifestations according to the disease phenotype, patient's age, and lifestyle. However, most patients pursue medical care because of the clinical symptoms of PCOS, such as hyperandrogenism, menstrual irregularities and infertility. Recent studies have shown that PCOS is associated with 80% of anovulatory infertility; however, the precise mechanism of PCOS-induced anovulation is still undetermined. The treatment strategies of PCOS are symptomatic depending mainly on the desired goals and clinical benefits. Life style intervention is still the first line treatment option for overweight females seeking pregnancy. In addition, there are many pharmacological agents that could be added to induce ovulation such as metformin, and clomiphene citrate. Nowadays, many patients preferred to use some herbal medicine that was proved to have potential therapeutic benefits in many studies in the management of PCOS. The purpose of this review was to discuss PCOS-induced infertility and the available therapeutic options as well as the impact of COVID-19 infection on the success of fertility attempts. To address this purpose, Pubmed, Scopus, EMBASE and Google databases were searched for studies discussing PCOS-induced infertility. The literature search revealed the proper therapeutic plans to treat PCOS-induced infertility, and that treatment should be modified according to patient's complaints, reproductive desires, and disease phenotypes. In conclusion, the use of specific therapeutic agents and patients' adherence to lifestyle interventions could help patients recover their reproductive and metabolic health.

CD27-IgD- B cells might portray an exhausted B cell phenotype resulting in lack of response to checkpoint inhibitor treatment in NSCLC

Background Checkpoint inhibitor (CI) therapy has revolutionized the therapy landscape of NSCLC. However, why some patients do not respond to CI therapy remains unknown. The correlation between intra-tumoral B cell follicles and response to CI therapy has been established. B cell follicles within the lymph node become more dispersed with age and CD27-IgD- B cells (DNBc) are described to be age-associated. Moreover, DNBc are abundant in chronic infection, elderly, long COVID and auto-immunity and are described to be anergic and exhausted and often lack expression of CD21. DNBc are expanded in NSCLC tumors compared to healthy lung tissue and inversely correlate to switched memory B cells in the tumor. In this study we explored if there is a correlation between this B cell subtype in peripheral blood of NSCLC patients and response to CI therapy. Methods Patients treated with CIs within the Erasmus Medical Center were included in a prospective observational immunomonitoring study. Nineteen NSCLC patients treated with either Pembrolizumab (Pem) or Nivolumab and 5 healthy controls (HC) were selected. Pem was given in 6/11 responding patients (R) and 5/8 non-responding patients (NR). Peripheral blood mononuclear cells (PBMC) were collected before start of treatment and characterized by multicolor flow cytometry. Results HC and R showed a similar pattern in most B cell subsets. NR had significantly lower proportion of B cells within the PBMC fraction than Rand HC (R: 7.14%, NR: 2.91%, HC: 10.60%). In addition, NR had a significantly higher frequency of DNBc than R and HC (R: 9.43%, NR: 23.78%, HC: 7.19%) and there was no correlation between age and DNBc. The frequency of DNBc correlated positively with lack of CD21 expression (r2: 0.83) and expression of Ki67 (r2: 0.54) both in NR, Rand HC. The frequency of Ki67+CD21-DNBc within the B cell fraction was higher in NR than in R and HC (NR: 18.34%, R: 3.51%, HC: 0.67%). Conclusions We are the first to describe that frequencies of DNBc are higher in NR compared to R and HC. Specifically, Ki67+CD21-DNBc are increased in NR and might reflect an anergic, exhausted B cell phenotype. The absence of a correlation between age and DNBc could suggest that the increase in DNBc is induced by the tumor. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure D. Dumoulin: Financial Interests, Personal, Other: Roche, BMS, MSD, AstraZeneca, Novartis. J.G. Aerts: Financial Interests, Personal, Research Grant: Amphera, Roche, Eli Lilly;Financial Interests, Personal, Advisory Board: Amphera, Bristol-Myers Squibb, Eli Lilly, MSD, Roche;Financial Interests, Personal, Ownership Interest: Amphera;Financial Interests, Personal, Other: Takeda. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

The situation of gynecological cancer before and after COVID-19 pandemic years in Kosovo

Background: On March 2020, the federal government of Kosovo declared a nationwide lockdown due to the COVID-19 pandemic until May 2020. Since the lockdown, examinations and routine checkups have been restricted. This resulted in a severe decline in patient referrals to the hospitals. We want to assess the impact of the COVID-19 pandemic on the rate of newly diagnosed gynecological cancers. Method(s): The data are taken from our patient database. Data from 752 patients from the only cancer centre in Kosovo with newly diagnosed gynaecological cancer between 2019, 2020 and 2021 were collected. Incidence, age group, stages of diagnosis and geographical distribution were compared between the time before and after the COVID-19 outbreak. Result(s): Our results showed a slight decline in newly diagnosed cancers in 2020 as compared with 2019 and 2021: -17 % in 2020 versus an increase of 18% in 2019. We expected to have a major increase in 2021 but data shows that it was a slight increase of 17%. As we not expected after the COVID-19 pandemic we have a strong decline of metastatic new cases of 39% in 2021 compared to 2020 and a 60% decline in 2020 compared to 2019. The results show a slight increase of 13 % in the early stages from 2020 to 2021 and the same rates come up from 2019 to 2020. In all three years in a row the dominant type of cancer according to localization is corpus uteri then cervix uteri and ovarian cancer with respectively 39%, 26%, and 33% in 2019, 36%, 33%, and 29% in 2020 and the last, 40%, 26% and 32% in 2021. The groupages have a slight shift from 45-49 years old the peak of new cases in 2021. Conclusion(s): The lockdown led to a slight decrease in the number of newly diagnosed cases. The decreased accessibility of the medical services has not led to significant higher number of metastatic new diagnosed cases, on contrary lower metastatic cases and higher number of early cases and slight increase on advanced cases were presented in 2021. The impact on incidence were not significantly higher in 2021 despite the lockdown. Therefore, new strategies to manage early cancer detection are needed to optimize cancer care in a time of pandemic in the future. Effective, appropriate and affordable cancer prevention and control strategies are urgently needed in Kosovo for gynaecological cancer especially cervical cancer. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology

Polycystic Ovary Syndrome and COVID-19.

Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenism, obesity, chronic low-grade inflammation, abnormalities in carbohydrate and lipid metabolism, vit. D deficiency and gut microbiota dysbiosis. Each of the aforementioned disturbances might be considered as a risk factor for increased SARS-CoV-2 susceptibility and more severe COVID-19 infection in women with PCOS. Hyperandrogenism is thought to play an essential role for determining the grade of susceptibility as well as the risk of severe COVID-19 infection in PCOS. It could be explained by the expression of a specific cellular co-receptor - transmembrane serine protease-2 (TMPRSS2), the process of androgen-dependent immune modulation and that of the stimulated renin-angiotensin system (RAS). Android obesity, commonly seen in PCOS, represents a condition of chronic low-grade inflammation that leads to the development of immune dysfunction and increased sensitivity to SARS-CoV-2 among the carriers of this syndrome. In addition, vit. D deficiency and gut dysbiosis have been described as other potential pathophysiological factors contributing to an increased risk for severe COVID-19 in women with PCOS.Copyright © 2022 Medical Information Center. All rights reserved.

The impact of COVID-19 on gynecological cancer diagnoses in Greece

Background: It has been almost three years since the COVID-19 outbreak, yet evidence of its impact on the cancer care landscape remains scant. The present single-center study examines patterns in gynecological cancer diagnoses before and during the pandemic. Method(s): All female patients diagnosed in our academic hospital with gynecological cancer, between January 2017 and December 2020, were retrospectively identified. Pre-defined subgroup analyses were performed in patients who had been newly diagnosed during 2020 and in the pre-pandemic 3-year period. The study was approved by the Institutional Ethical Committee and was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization for Good Clinical Practice. Result(s): In total, 1,193 women were included in this case-control study;1,001 (83.91%) were identified in the pre-pandemic period as a control, while 192 (16.09%) cases were allocated in the pandemic group. The two cohorts were similar regarding demographic and clinical characteristics. For the pre-pandemic period, the mean yearly number of patients with newly identified cancer was highest for endometrial (149;44.61%), followed by ovarian (92;27.5%) carcinomas. During the first year of the pandemic, the number of new diagnoses significantly decreased by 42.5% (from 334 to 192) for all types of malignancies combined (one sample t-test p-value= 0.014). Declines ranged from 36.96% to 49% for ovarian and endometrial cancer, respectively. Conclusion(s): This is the first study to appraise a timely snapshot of the effect of COVID-19 on newly diagnosed gynecological tumors in a European Society of Gynaecological Oncology (ESGO)-certified center in Greece, demonstrating an alarmingly sharp decline in the number of new cases during the pandemic. It is of utmost importance the gynecologic oncologists to ensure the continuum of care for their patients. [Formula presented] Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology

Clinical and immunological impact of booster immunization with recombinant mRNA vaccines for SARS-CoV-2 in patients with pemphigus and bullous pemphigoid

Vaccines based on recombinant mRNA technology helped to control the pandemic caused by the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). Clinical trials for showed that these vaccines are safe and effective and promote a strong type 1 driven T cell response. Yet, several reports claimed that SARS-CoV-2 mRNA vaccination might favor the onset, worsening or the reactivation of autoimmune disorders like pemphigus and bullous pemphigoid. However, no study demonstrated a direct immunological link between mRNA vaccination and disease appearance/worsening. We aimed to analyze the immunological and clinical effects exerted by mRNA booster vaccinations for SARS-CoV-2 in a cohort of patients with pemphigus (n=9), bullous pemphigoid (n=4) and in healthy individuals (n=5). Patients and healthy individuals were monitored at baseline, and after two and four weeks of mRNA vaccination. We assessed the clinical disease status, antibodies against the SARS-CoV-2 spike protein, antibody levels for BP180/230, DSG1/3 and tetanustoxoid. We also determined the distribution of peripheral T helper / T follicular cell subsets, intracellular cytokine production of T cells and cytokine serum levels. Our results show that booster vaccination increased anti spike protein IgG, while tetanustoxoid igC and skin-specific autoantibody titers were not or minimally affected. We observed an increase in Th1/Th17.1 cells, together with an increase in the intracellular production of IFN-gamma, IL-4 and IL-21 in peripheral T cells of pemphigus patients. Importantly, clinical activity in both remittent patients and in patients with active disease remained stable. In summary, vaccination with mRNA vaccines induced a specific activation of the humoral system with production of protective antibodies against the Sars-CoV-2 spike protein without affecting autoimmune disease activity in patients with pemphigus and bullous pemphigoid.Copyright © 2023