Background and Purpose:To the best of our knowledge, no information is available regarding the treatment of vulvovaginal candidiasis in gynecological practices. The goal of this study was to analyze the prevalence of vulvovaginal candidiasis (VVC) and the drugs prescribed for the treatment of this condition in women followed in gynecological practices in Germany.Materials and Methods:All the women followed in 262 gynecological practices between November 2014 and October 2016 were included in this study. The first outcome was the prevalence of patients diagnosed with VVC during this period. The second outcome was the prevalence of women with VVC who received an appropriate vaginal or systemic antimycotic prescription within 30 days after their first VVC diagnosis. Covariables included the use of gynecological/systemic antibiotics, consumption of oral/vaginal contraceptives, cancer, pregnancy, diabetes, and psychiatric diseases including depression, anxiety, and adjustment and somatoform disorders.Results:Between 2014 and 2016, 954,186 women were followed in gynecological practices, and 50,279 (5.3%) women were diagnosed with VVC during the same period. The use of gynecological antibiotics (OR=2.88), systemic antibiotics (OR=1.45), oral contraceptives (OR=1.74), and vaginal contraceptives (OR=1.84) were associated with an increase in the risk of VVC diagnosis. Cancer (OR=1.20) and pregnancy (OR=1.59) were additional risk factors. Approximately 75% of women diagnosed with VVC received an antimycotic prescription. The three most frequently prescribed drugs were clotrimazole (72%), fluconazole (14%), and nystatin (6%).Conclusion: More than 5% of women were diagnosed with VVC and the majority of them received an appropriate prescription.

T-cell engaging immunotherapies exert unprecedented single-agent activity in Multiple Myeloma (MM), thereby putting a yet unexplored selective pressure on the clonal architecture. In this study, we report on homozygous BCMA (TNFRSF17) gene deletion after BCMA targeting T-cell redirecting bispecific antibody therapy in a heavily pretreated MM patient. Loss of BCMA protein expression persisted over subsequent relapses, with no response to anti-BCMA antibody drug conjugate (ADC) treatment. In light of the multiple alternative targets that currently emerge in addition to BCMA, we extended our analyses to delineate a more complete picture of genetic alterations that may impact immuno-therapy targets in MM. We performed WGS and RNAseq in 100 MM patients (50 NDMM and 50 RRMM) and identified a significant proportion of patients with aberrations in genes encoding for immunotherapy targets, and GPRC5D ranked first with 15% heterozygous deletions, followed by CD38 (10%), SDC1 (5%) and TNFRSF17 (4%). Notably, these heterozygous deletions did not lower the expression levels of respective genes, but may represent a 'first hit' that drives the acquisition of homozygous deletions and, subsequent antigen-loss relapse upon targeted immunotherapy. In summary, we show pre-existing vulnerability in genes encoding for immuno-targets prior to and homozygous deletions after T-cell engaging immunotherapy.

Pseudo-progression and flare-up phenomena constitute a novel diagnostic challenge in the follow-up of patients treated with immune-oncology drugs. We present a case study on pulmonary flare-up after Idecabtagen Vicleucel (Ide-cel), a BCMA targeting CAR T-cell therapy, and used single-cell RNA-seq (scRNA-seq) to identify a Th17.1 driven autoimmune mechanism as the biological underpinning of this phenomenon. By integrating datasets of various lung pathological conditions, we revealed transcriptomic similarities between post CAR T pulmonary lesions and sarcoidosis. Furthermore, we explored a noninvasive PET based diagnostic approach and showed that tracers binding to CXCR4 complement FDG PET imaging in this setting, allowing discrimination between immune-mediated changes and true relapse after CAR T-cell treatment. In conclusion, our study highlights a Th17.1 driven autoimmune phenomenon after CAR T, which may be misinterpreted as disease relapse, and that imaging with multiple PET tracers and scRNA-seq could help in this diagnostic dilemma.

Background and Purpose: To the best of our knowledge, no information is available regarding the treatment of vulvovaginal candidiasis in gynecological practices. The goal of this study was to analyze the prevalence of vulvovaginal candidiasis (VVC) and the drugs prescribed for the treatment of this condition in women followed in gynecological practices in Germany. Materials and Methods: All the women followed in 262 gynecological practices between November 2014 and October 2016 were included in this study. The first outcome was the prevalence of patients diagnosed with VVC during this period. The second outcome was the prevalence of women with VVC who received an appropriate vaginal or systemic antimycotic prescription within 30 days after their first VVC diagnosis. Covariables included the use of gynecological/systemic antibiotics, consumption of oral/vaginal contraceptives, cancer, pregnancy, diabetes, and psychiatric diseases including depression, anxiety, and adjustment and somatoform disorders. Results: Between 2014 and 2016, 954,186 women were followed in gynecological practices, and 50,279 (5.3%) women were diagnosed with VVC during the same period. The use of gynecological antibiotics (OR=2.88), systemic antibiotics (OR=1.45), oral contraceptives (OR=1.74), and vaginal contraceptives (OR=1.84) were associated with an increase in the risk of VVC diagnosis. Cancer (OR=1.20) and pregnancy (OR=1.59) were additional risk factors. Approximately 75% of women diagnosed with VVC received an antimycotic prescription. The three most frequently prescribed drugs were clotrimazole (72%), fluconazole (14%), and nystatin (6%). Conclusion: More than 5% of women were diagnosed with VVC and the majority of them received an appropriate prescription.

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