Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes.

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014-12/2021). Primary outcomes included live birth, miscarriage, or transfer failure. We documented IVIg side effects and maternal/fetal outcomes. Logistic regression analysis was used to assess for association of IVIg exposure with outcomes and adjust for confounders. The study included 143 patients, with a 2:1 ratio of controls to patients receiving IVIg treatment. Patient characteristics were similar between groups. There was higher live birth rate (LBR) in patients receiving IVIg (32/49; 65.3%) compared to controls (32/94; 34%); p < 0.001). When stratifying patients into moderate and severe uRIF (respectively 3-4 and [Formula: see text] 5 previous good quality blastocyst transfer failures), only patients with severe uRIF benefited from IVIg (LBR (20/29 (69%) versus 5/25 (20%) for controls, p = 0.0004). In the logistic regression analysis, IVIg was associated with higher odds of live birth (OR 3.64; 95% CI 1.78-7.67; p = 0.0004). There were no serious adverse events with IVIg. IVIg can be considered in well selected patients with [Formula: see text] 5 previous unexplained, high quality blastocyst transfer failures. A randomized controlled trial is needed to confirm these findings.

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss.

PROBLEM: Recurrent pregnancy loss (RPL) affects up to 4% of couples attempting to conceive. RPL is unexplained in over 50% of cases and no effective treatments exist. Due to the immune system's pivotal role during implantation and pregnancy, immune-mediated RPL may be suspected and immunomodulatory treatments like intravenous immunoglobulin (IVIg) have been administered but remain controversial. The goal of our study was to evaluate our center's 6 year-outcomes and to develop a framework for IVIg use in RPL. METHOD OF THE STUDY: Retrospective, single-center cohort study. All patients having received IVIg for unexplained RPL at the McGill Reproductive Immunology Clinic (MRIC) from January 2014 to December 2020 were included if maternal age was <42 years, body mass index (BMI) < 35 kg/m2 , non-smoker and having had ≥3 consecutive RPL despite previous treatment with aspirin and progesterone. IVIg 0.6-0.8 g/kg was given prior to conception and monthly during pregnancy until 16-20 weeks' gestation. We compared IVIg treated patient's outcomes to a separate "natural history cohort". This cohort was composed of patients consulting at the McGill recurrent pregnancy loss clinic and the MRIC over a 2-year period (January 2020 to December 2021) with similar inclusion criteria as the treatment cohort but did not receive IVIg or other immunomodulatory treatments. The association of IVIg with outcomes (compared to no IVIg) was evaluated among the groups of patients with primary RPL and secondary RPL. The primary outcome was live birth rate (LBR), secondary outcomes included IVIg safety, obstetrical, and neonatal complications. RESULTS: Among 169 patients with unexplained RPL that were included in the study, 111 had primary RPL (38 exposed to IVIg and 83 controls) and 58 had secondary RPL (nine exposed to IVIG and 49 controls). Among patients with primary RPL (n = 111), the LBR was 64.3% (18/28) among patient exposed to IVIg compared to 43.4% (36/83) in controls (p = 0.079); regression analysis adjusting for BMI and number of previous miscarriages showed benefit favoring the use of IVIg (OR = 3.27, CI 95% (1.15-10.2), p = 0.03) when evaluating for live birth. In the subgroup of patients with ≥5 previous RPL and primary RPL (n = 31), IVIg was associated with higher LBR compared to control (10/15 (66.7%) vs. 3/16 (18.8%); p = 0.0113) but not the in the sub-group of patients with <5 miscarriages and primary RPL (8/13 (61.5%) vs. 33/67 (49.3%); p = 0.548). IVIG treatment did not improve LBR in patients with secondary RPL in our study (3/9 (33.3%) vs. 23/49 (47%); p = 0.495). There were no serious adverse events in the IVIg treatment group, obstetrical/neonatal complications were similar between groups. CONCLUSION: IVIg may be an effective treatment for patients with RPL if appropriately used in specific groups of patients. IVIg is a blood product and subject to shortages especially with unrestricted off-label use. We propose considering IVIg in well-selected patients with high order RPL who have failed standard medical therapy. Further mechanistic studies are needed to understand immune-mediated RPL and IVIg's mode of action. This will enable further refinement of treatment criteria and the development of standardized protocol for its use in RPL.

Genetic predisposition to depression and inflammation impacts symptom burden and survival in patients with head and neck cancer: A longitudinal study.

OBJECTIVE: The primary purpose of this study was to investigate the contribution of genetic predispositions to depression and inflammation, as measured through polygenic risk scores, on symptom burden (physical and psychological) in patients with head and neck cancer in the immediate post-treatment period (i.e., at three months post-diagnosis), as well as on 3-, 6-, 12-, 24- and 36-month survival. METHODS: Prospective longitudinal study of 223 adults (72 % participation) newly diagnosed with a first occurrence of primary head and neck cancer, paired with genetic data (Illumina PsychArray), validated psychometric measures, Structured Clinical Interviews for DSM Disorders (SCID-I), and medical chart reviews. RESULTS: Symptom burden at 3 months was predicted by (R2 adj. = 0.38, p < 0.001): a baseline SCID-I Anxiety Disorder (b = 1.69, B = 0.23, 95%CI = 0.43-2.94; p = 0.009), baseline levels of HADS anxiety (b = 0.20, B = 0.29, 95%CI = 0.07-0.34; p = 0.003), the polygenic risk score (PRS) for depression (b = 0.66, B = 0.18, 95%CI = 0.003-1.32; p = 0.049), and cumulated dose of radiotherapy (b = 0.002, B = 0.46, 95%CI = 0.001-0.003; p < 0.001). When controlling for factors known to be associated with cancer survival, patients with a higher PRS associated with depression and inflammation, respectively, presented higher risk of death within 36 months (b = 1.75, Exp(B) = 5.75, 95%CI = 1.55-21.27, p = 0.009 and b = 0.14, Exp(B) = 1.15, 95%CI = 1.01-1.30, p = 0.03). CONCLUSIONS: Our results outline three potential pathways of symptom burden in patients with head and neck cancer: a genetic predisposition towards depression; an initial anxiety disorder upon being diagnosed with cancer or high levels of anxiety upon diagnosis; and a dose-related response to radiotherapy. One may want to investigate early interventions in these areas to alleviate symptom burden in patients faced with a life-threatening disease, as well as consider targeting genetic predisposition towards depression and inflammation implicated in survival. The high prevalence of distress in patients with head and neck cancer is an opportunity to study genetic predispositions, which could potentially be broadly generalized to other cancers and diseases.

Immunomodulation for unexplained recurrent implantation failure: where are we now?

In brief: Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Abstract: Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

Physical health status of music students in a post-secondary institution: A cross-sectional study.

BACKGROUND: Musicians' health is an essential field of healthcare that is specifically tailored to the needs of musicians, which encompasses multiple facets of health. OBJECTIVE: The research seeks to determine the prevalence of physical injuries in music students and musicians, and to identify possible causes. METHODS: A previously unvalidated 42-item survey was distributed to music students, non-music students, and professional musicians. The questions addressed demographics, physical health, mental health, medication use, and interest in musicians' health. The study was conducted from Fall semester 2017 to Winter semester 2019 at McGill University, with analysis completed in August 2019. RESULTS: A total of 585 complete responses were obtained. Music students (35%) had higher prevalence of physical injuries than non-music students (18%), and professional musicians had the highest prevalence (56%). Multiple factors dictate the prevalence of physical injuries among musicians, including gender, age, program of enrollment, and instrument of choice. Of note, daily duration of practice was not one of these factors. CONCLUSIONS: Several factors were identified through this cross-sectional analysis to be associated with musicians' physical injuries. These findings can serve as a foundation through which physicians and post-secondary institutions may implement changes to better enhance the physical health of musicians. It also cast doubts on previous assumptions associated with physical injury of musicians.

Lived Experience and Patient Advocacy Module: Curriculum and Faculty Guide.

INTRODUCTION: Medical teachers frequently tell learners how some of the greatest challenges in clinical care are not associated with the scientific details of biomedicine but are instead related to patient interactions and the human dimensions of illness and recovery. Beyond providing direct care, physicians sometimes serve as advocates and supporters for their patient as the patient navigates through the health care system. Opportunities to discuss and reflect on these aspects of medical practice may not arise in the course of clinical experiences. METHODS: This video module and accompanying lesson plan provide the basis for a structured session on patient-physician communication and patient advocacy. In the video, learners hear from a patient who experienced a life-changing medical condition and who faced challenges both before diagnosis and during a long recovery. The video provides a basis for vital discussions about the patient-physician relationship, highlighting the importance of clear and continuing communication. RESULTS: Students indicated that this module effectively provided a patient perspective. The video format and fast pace of the presentation appealed to them. DISCUSSION: This module is ideally suited for use as a stimulus for a facilitated small-group discussion with medical students. It can be presented within a 1-hour session. It can also be used as a freestanding module for independent study. Though the patient suffered from a specific medical condition-a pituitary tumor and related complications-students do not need to be knowledgeable about those conditions or have in-depth clinical experience to readily comprehend the messages in this lesson.

Preparation and characterization of new anti-PSMA monoclonal antibodies with potential clinical use.

Monoclonal antibodies with high specificity for prostate cancer tissue are of interest for diagnostic and therapeutic applications employing targeted therapy. The prostate-specific membrane antigen (PSMA) is a protein predominantly found in epithelial cells of prostate tissue origin and its expression correlates with tumor aggressiveness. Here, we report the development and characterization of new antibodies against PSMA. Murine monoclonal antibodies (MAb) were obtained by immunizing mice with a peptide corresponding to PSMA extracellular residues 490-500 -- GKSLYESWTKK (PSMA(490-500)). The MAbs react specifically to PSMA and to the prostate cancer cell line LNCaP with an affinity for PSMA in the low nanomolar range. This study also demonstrates the potential use of these antibodies for targeted drug delivery to prostate cancer cells. Nanomolar concentrations of PSMA-specific MAb in association with a molecule with cytotoxic potential were sufficient to allow for binding and uptake by LNCaP cells within minutes, leading to complete cell death within 3 days. These MAbs have potential clinical value in the development of diagnostic and therapeutic applications for prostate cancer.

Cyclooxygenase-2 expression in uveal melanoma: novel classification of mixed-cell-type tumours.

BACKGROUND: The expression of cyclooxygenase-2 (COX-2), an inducible prostaglandin (PG) synthase, has been investigated in various human malignant diseases, such as cutaneous melanoma. We investigated the expression of COX-2 in uveal melanoma and related the findings to prognostic factors. METHODS: In 40 cases of uveal melanoma, immunostaining for COX-2 was done. COX-2 expression was related to histopathological prognostic markers, such as cell type, the presence of lymphocytic infiltration and vascular closed loops in the tumour, and cytomorphometry results. RESULTS: COX-2 expression was found in 58% of the cases, and it correlated with markers of poor prognosis, such as epithelioid cell type and the presence of lymphocytic infiltration and vascular closed loops. The uveal melanomas expressing COX-2 had larger nuclei, as determined by cytomorphometry. INTERPRETATION: Whereas epithelioid tumours carry a worse prognosis than spindle cell tumours, until now it has not been possible to give a strong indication of prognosis in mixed-cell tumours. This study showed that mixed-cell tumours, representing the majority of uveal melanomas, may be further subclassified according to COX-2 expression, which serves as a marker of poor prognosis. The role of COX-2 in uveal melanoma should be further elucidated, and the use of COX-2 inhibitors warrants investigation as adjuvant treatment for this life-threatening malignant disease.