T Cell Exhaustion and Activation Markers in Pancreatic Cancer: A Systematic Review.

BACKGROUND: T cell exhaustion and activation markers are helpful in determining the therapies and predicting the overall survival in pancreatic cancer (PC) patients. PURPOSE: In this systematic review, we have addressed two questions, how do these markers differ in their expression levels in PC patients and healthy individual and correlating the expression level of these markers with the cancer stage. METHODS: The systematic review was registered with Prospective Register of Systematic Reviews (PROSPERO) with registration number "CRD42022246780." All the included articles were obtained from three databases, PubMed, MEDLINE, and Cochrane, published from January 2010 to 26th May 2022. Two independent reviewers followed the PRISM protocol and reviewed and extracted data from the included articles. RESULTS: PD-1 and CTLA-4 were the most studied markers in this field. A clear elevation in the expression of PD-1, CTLA-4, TIM-3, LAG-3, and TIGIT was found in most of the studies. CD69, CD25, and HLA-DR expression was found to be upregulated after chemotherapy and immunotherapy. CD25 was the only marker analyzed against cancer progression, in a single study. No study compared the expression of exhaustion and activation markers (except CD69) with the cancer progression of the tumor stage. CONCLUSION: Since the exhaustion markers are upregulated in patients, single or multiple markers can be targeted in immunotherapies. Knowledge of the dynamics of these markers at various cancer stages will help in determining the right immunotherapy for pancreatic cancer patients. Stage-wise comparison could also be made possible by developing in vitro models.

Ethnic discordance in serum anti-Müllerian hormone in European and Indian healthy women and Indian infertile women.

RESEARCH QUESTION: Does anti-Müllerian hormone (AMH) differ between healthy European and Indian women, and are potential ethnic differences modified by infertility diagnosis? DESIGN: Cross-sectional analysis of three prospectively recruited cohorts (n = 2758); healthy European women (n = 758), healthy community cohort from Kolhapur, India (n = 400) and infertility cohort from Kolhapur, India (n = 1600). AMH was determined by assay. Ethnicity, age and cause of infertility were modelled using additive quantile regression models. RESULTS: Healthy Indian women had lower AMH than their healthy European counterparts (population estimates 20.0% lower [95% CI 7.2-36.5]), with increasing discordance with increasing age; at 25 years AMH was 11.9% lower (95% CI 9.4-14.1), increasing to 40.0% lower (95% CI 0-64.6) by age 45. Comparison of healthy and infertile Indian women revealed differences that were related to cause of infertility. Women whose male partner had severe oligoasthenoteratozoospermia (n = 95) had similar AMH to controls; women with polycystic ovary syndrome (n = 220) had higher AMH, especially in those <30 years, and in women with a principal diagnosis of unexplained infertility (n = 757) AMH was lower (median difference 22.6% lower; 95% CI 9.1-37.7) than controls. CONCLUSIONS: AMH is substantially lower in healthy Indian women at all ages than their European counterparts. Infertile Indian women have variable differences in AMH from healthy Indian controls, with the extent and direction of differences primarily reflecting the underlying cause of infertility. Recognition of ethnic and cause-specific differences are critical to ensure accurate contextualizing of results and clinical outcomes for patients.

Resuming Assisted Reproduction Services during COVID-19 Pandemic: An Initial Indian Experience.

BACKGROUND: The pandemic of COVID-19 has affected many countries and medical services including assisted reproductive treatment (ART) have been hampered. AIM: The study was conducted to assess the preparedness of ART clinics and staff to resume services; patients' reasons to initiate treatment; and key performance indicators (KPIs) of ART laboratories during the pandemic. SETTING AND DESIGN: This was a semidescriptive, prospective study in two private in vitro fertilization (IVF) clinics in Maharashtra, India, when COVID-19 testing for asymptomatic people was unavailable. MATERIALS AND METHODS: Time required for replenishing consumables and clinic preparedness to function under "new norms" of pandemic was documented. Infection mitigation measures and triaging strategy were evaluated. KPIs following resumption were analyzed. The Student's t-test was performed for comparing parameters. RESULTS: Thirty percent of the patients consulted through telemedicine accepted or were eligible to initiate treatment on clinic resumption. Lack of safe transport and financial constraints prevented majority from undergoing IVF, and 9% delayed treatment due to fear of pandemic. With adequate training, staff compliance to meet new demands was achieved within a week, but procuring consumables and injections was time-consuming. Fifty-two cycles of IVF were performed including fresh and frozen embryo transfers with satisfactory KPIs even during pandemic. Conscious sedation and analgesia during oocyte retrieval were associated with reduced procedure time and no intervention for airway maintenance compared to general anesthesia. Self-reported pain scores by patients ranged from nil to mild on a graphic rating scale. CONCLUSIONS: This study provides practical insight for the resumption of IVF services during the COVID-19 pandemic.

Impact of dehydroepiandrosterone on clinical outcome in poor responders: A pilot study in women undergoing in vitro fertilization, using bologna criteria.

OBJECTIVE: To evaluate the role of dehydroepiandrosterone (DHEA) supplementation in women with poor ovarian response (POR) undergoing in vitro fertilization (IVF). DESIGN: Prospective case-control study. SETTING: Private tertiary fertility clinic. MATERIALS AND METHODS: 31 infertile women with POR diagnosed as per the Bologna criteria. INTERVENTIONS: DHEA supplementation for 2 months and a subsequent IVF cycle, after two previous IVF cycles with POR. MAIN OUTCOME MEASURES: Dose and duration of gonadotropin therapy, oocyte yield, embryo number and quality, pregnancy and live birth rate. RESULTS: No difference was seen in gonadotropin requirement before and after DHEA supplementation. There was a significant increase in total and metaphase II oocytes (5.9 ± 0.68 vs. 2.73 ± 0.24; 4.45 ± 0.47 vs. 2.09 ± 0.26), fertilization (3.65 ± 0.49 vs. 2.00 ± 0.27), Grade I embryos (1.52 ± 0.25 vs. 0.55 ± 0.18), pregnancy rate (30% vs. 9.1%) and live birth rate (25% vs 0%) in those who completed the cycle, following DHEA supplementation. CONCLUSIONS: Dehydroepiandrosterone supplementation results in an improvement in oocyte yield, embryo quality, and live birth rate in a group of women with POR having undergone at least two previous failures due to POR.

An ideal oocyte activation protocol and embryo culture conditions for somatic cell nuclear transfer using sheep oocytes.

Pluripotent stem cells are possibly the best candidates for regenerative medicine, and somatic cell nuclear transfer (SCNT) is one of the viable options to make patient-specific embryonic stem cells. Till date efficacy of SCNT embryos is very low and requires further improvement like ideal oocyte activation and in vitro culture system. The aim of the present study was to evaluate ideal oocyte activation using different stimulation protocols and to study the effect of cumulus co-culture conditions on embryo development. Results demonstrate that between electric stimulation and chemical stimulation using calcium ionomycin and ionophore, best oocyte activation was obtained using calcium ionomycin (5 microM for 5 min) which resulted in 83% cleavage followed by 7% of early blastocyst which further increased to 15% when a cumulus bed was also introduced during embryo culture. Sequential modified Charles Rosenkrans 2 (mCR2) medium was used for embryo culture in which glucose levels were increased from 1 mM to 5 mM from Day 3 onwards. SCNT using cumulus cells as donor somatic cell, calcium ionomycin to activate the reconstructed oocyte and embryo culture on a cumulus bed in sequential mCR2 medium, resulted in the development of 6% embryos to early blastocyst stage. Such technological advances will make SCNT a viable option to make patient-specific pluripotent stem cell lines in near future.