Anti-goat antibodies as a rare cause of high gonadotropin levels during menopausal transition

Abstract

Objective: To understand the origin of extremely high gonadotropin levels in a perimenopausal woman.

Methods: A 52-year-old woman with a 2?months of amenorrhea followed spontaneous menstrual cycles recovery was referred to our outpatient clinic with elevated follicle-stimulating hormone (FSH, 483 mUI/ml), luteinizing hormone (LH, 475 mUI/ml) and prolactin (PRL, 173?ng/ml). She was known to take levosulpiride. The gonadotropin levels did not fit with the clinical features.

Results: A gonadotroph tumor was ruled out. Further analysis confirmed constantly high FSH, LH and PRL levels. The measurements were repeated using different analytical platforms with different results. After serial dilutions, nonlinearity was present suggesting an immunoassay interference. After post-polyethylene glycol recovery, hormone levels appeared in the normal range. Anti-goat antibodies were recognized in the serum of the patient.

Conclusions: This case report shows a case of falsely abnormal high gonadotropin and PRL levels in a woman during menopause transition. In the clinical practice the evaluation of gonadotropin profile is not recommended at this age, but the abnormal levels stimulated further evaluation. An interference in the assay due to anti-goat antibodies resulted in abnormally high level of FSH and LH. A strict collaboration between clinicians and the laboratory is needed, when laboratory findings do not correspond to clinical findings.     

Neuroendocrine,epigenetic, and intergenerational effects of general anesthetics

The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.     

Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles

Background Immune checkpoint blockers (ICBs) activate CD8⁺ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8⁺ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10⁻⁶). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8⁺ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma     

A randomized study on the effect of modified behavioral activation treatment for depressive symptoms in rural left-behind elderly

Objective: To evaluate the effectiveness of a modified behavioral activation treatment (MBAT) intervention on reducing depressive symptoms in rural left-behind elderly.

Method: This is a randomized study registered in Chinese Clinical Trial Registry (ChiCTR-IOR-17011289). Eighty rural left-behind elderly people who had a Geriatric Depression Scale (GDS) score between 11 and 25 were randomly assigned to the intervention (n?=?40) and control group (n?=?40). The intervention group received both MBAT and regular treatment for 8 weeks while the control group received regular treatment. Both groups were assessed with the GDS, Beck Anxiety Inventory (BAI), and Oxford Happiness Questionnaire (OHQ) at baseline, immediately post-intervention, and at 3 months post-intervention.

Results: There were a total of 73 participants that completed the intervention. The scores of GDS and BAI decreased significantly, but the scores of OHQ increased significantly in the intervention group after 8 sessions of MBAT (P?<?.01). The reduction in depression symptoms after the intervention was maintained at the 3-month follow-up. Significant differences in GDS, BAI, and OHQ scores were observed between the intervention group and the control group (P?<?.01).

Conclusion: MBAT produced a significantly greater reduction in depressive symptoms than regular care in rural left-behind elderly.

Clinical or methodological significance of this article: A modified behavioral activation (BA) psychotherapy can significantly reduce the recurrence and seriousness of depression symptoms in the left-behind elderly with mild to moderate depression. This study also suggests that further study of the MBAT as an intervention will provide a direction for the management of mental health in rural left-behind elders.