Discrepancy in PD-L1 expression between primary and metastatic tumors in two patients with recurrent cervical cancer.

Introduction: Pembrolizumab is an immunotherapy approved for use in patients with a combined positive score (CPS) greater than one with recurrent cervical cancer. In clinical practice, the CPS score is not typically analyzed in both primary and metastatic specimens. Case descriptions: Case 1A 42-year-old woman with history of an abnormal pap smears who presented with a large pelvic mass with initial biopsy of cervix demonstrating squamous cell carcinoma with negative PDL1 expression and a CPS score of 0. She underwent chemoradiation and presented three months after primary treatment completion with recurrence of squamous cell carcinoma and positive PD-L1 expression with a CPS score of 20. Pembrolizumab was added to cycle three of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She had progression on this regimen and was transitioned to tisotumab vedotin; however, ultimately opted to proceed with hospice secondary to failure to thrive.Case 2A 36-year-old woman with history of an abnormal pap smear in pregnancy and initial biopsy demonstrating endocervical adenocarcinoma, mucinous type. She underwent open radical hysterectomy, bilateral salpingectomy, bilateral oophorepexy, and bilateral pelvic lymph node dissection with subsequent adjuvant chemoradiation. Her initial pathology demonstrated positive PDL1 expression with CPS score of 15. She presented six months after completion of primary treatment with recurrence of endocervical adenocarcinoma, mucinous type and negative PD-L1 expression with a CPS score of < 1. Regardless of this discrepancy, pembrolizumab was added to cycle five of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She initially demonstrated a mixed response; however, ultimately progressed after eight cycles and was transitioned to tisotumab vedotin. Discussion: To our knowledge, discrepancies in PD-L1 expression in a matched setting between primary and metastatic tumors has only been reported once. This is the first case report describing these inconsistencies. Etiologies of and outcomes related to the discrepant expression of PD-L1 should be further studied.

Intrapartum Management in Maternal Brugada Syndrome.

Brugada syndrome is a genetic cardiac disease associated with increased risk of ventricular tachyarrhythmia and sudden cardiac arrest. Labor and delivery in this population poses management challenges of labor induction, analgesia, postpartum hemorrhage, and arrhythmic events. This case report describes a multidisciplinary approach to intrapartum management in maternal Brugada syndrome.

Fluconazole-Resistant Candida albicans Vaginal Infections at a Referral Center and Treated With Boric Acid.

OBJECTIVE: The authors investigate the incidence of clinical and mycological resistance of Candida albicans vulvovaginitis (VVC) at the Jefferson Vulvovaginal Health Center. They also review their experience with boric acid in the treatment of fluconazole-resistant VVC. METHODS: The authors conducted a retrospective chart review of all patients with C. albicans VVC diagnosed at the Jefferson Vulvovaginal Health Center between November 2019 and December 2021. Patients with clinically defined fluconazole resistance were identified. Information about demographics, in vitro susceptibility testing, and treatment outcomes with boric acid was obtained. RESULTS: Of 970 patients with vaginal C. albicans isolates, 71 (7.3%) with clinically defined fluconazole-resistant C. albicans infections were identified. Relevant demographics included 45.1% African American, 43.7% aged younger than 30 years, and 43.7% with body mass index less than 25. Of the 71 patients, 58 (81.7%) received vaginal boric acid treatment. The mycological and clinical cure rates were 85.7% and 73.7%, respectively. After successful boric acid treatment and negative yeast cultures, 14.3% of patients had a mycological recurrence within 3 months. Of 31 isolates with antifungal susceptibility testing, 83.9% (26/31) were found to have minimal inhibitory concentration results consistent with fluconazole resistance. CONCLUSIONS: In a tertiary care vulvovaginal health center, fluconazole-resistant Candida albicans VVC is by no means uncommon and usually responds in the short term to treatment with boric acid. However, in the absence of maintenance boric acid, recurrence of culture-positive VVC is likely.

The effect of hematopoietic stem cell transplantation on fertility and strategies for improvement.

Ovarian dysfunction is an important consequence of hematopoietic stem cell transplantation (HCT). Premature ovarian failure and infertility can severely impact the quality of life for the increasing number of female long-term survivors of HCT. Here, we review the impact of HCT on ovarian function, post-transplant fertility and birth outcomes, and the contemporaneous strategies to preserve fertility for these patients.

The impact of HLA donor-specific antibodies on engraftment and the evolving desensitization strategies.

The majority of contemporary allogeneic hematopoietic stem cell transplantation (HCT) procedures utilize partially HLA-mismatched stem cell grafts. Donor-specific anti-HLA antibodies (DSA) are associated with primary graft failure independent of the graft source, conditioning intensity and other patient and donor factors. Here we provide an update on testing and monitoring of DSA, review the impact of DSA on stem cell engraftment, and present promising desensitization modalities. Ultimately, we attempt to provide practical recommendations for DSA screening and mitigation strategies.