Adeno-Associated Virus-based Gene Therapy for Hemophilia A and B: A Systematic Review and Meta-Analysis.

Adeno-associated virus (AAV)-based gene therapy is an emerging treatment for hemophilia A (HA) and hemophilia B (HB). In this systematic review and meta-analysis, we searched for studies of adult males with severe or moderately severe HA or HB who received AAV-based gene therapy. Annualized bleeding rate (ABR), annualized infusion rate (AIR), total factor use, factor levels, and adverse events (AE) were extracted. Eight HA trials representing 7 gene therapies and 211 subjects and 12 HB trials representing 9 gene therapies and 184 subjects were included. For HA, gene therapy resulted in an annualized decrease of 7.58 bleeding events (95% CI -11.50 to -3.67) and 117.2 factor infusions (95% CI -151.86 to -82.53) compared to prior to gene therapy. Factor VIII level at 12 months ranged from 10.4 to 70.31 IU/mL by one-stage assay. HB gene therapies were associated with an annualized decrease of 5.64 bleeding events (95% CI -8.61 to -2.68) and 58.92 factor infusions (95% CI -68.19 to -49.65). Mean factor IX level at 12 months was 28.72 IU/mL (95% CI 18.78-38.66). Factor expression was more durable for HB than HA; factor IX levels remained at 95.7% of their peak whereas factor VIII levels fell to 55.8% of their peak at 24 months. The pooled percentage of subjects experiencing a serious AE was 19% (10-31%) and 21% (10-37%) for HA and HB gene therapies, respectively. No thrombosis or inhibitor formation was reported. AAV-based gene therapies for both HA and HB demonstrated significant reductions in ABR, AIR, and factor use.

Synchronous development of prostate sarcoma and squamous cell carcinoma following radiotherapy.

With the development of more sensitive screening tools, malignancies are being diagnosed at an earlier stage, resulting in earlier intervention and longer survival times. As a consequence, the long-term complications of cancer therapy are increasing in incidence, particularly second primary cancers from radiation therapy. Bladder and colorectal cancers are the most commonly reported malignancies secondary to radiation therapy for prostate cancer. We present the case of a 78-year-old patient with a remote history of prostate adenocarcinoma, status post brachytherapy, who subsequently developed both prostate sarcoma and prostate squamous cell carcinoma secondary to the prior treatment. Because his cancer was metastatic, he was not a candidate for surgery and was treated with chemotherapy and palliative radiation.

Exploring the Rare Etiology of Severe Anemia in an Immunocompromised Patient.

Pure red cell aplasia (PRCA) is a rare cause of profound anemia, marked by very low reticulocyte count and near to complete absence of erythroid precursor cells in the bone marrow. PRCA can be congenital such as in the case of children with Diamond- Blackfan anemia or acquired, which is often triggered by exposure to certain viruses or drugs. Management depends on the underlying etiology of PRCA. Here, we present the case of a young male with underlying acquired immunodeficiency syndrome, who presented with a hemoglobin of 2.6 g/dL, initially thought to be secondary to gastrointestinal blood loss, but was later discovered to have parvovirus-induced PRCA.

Dermatofibrosarcoma protuberans of the scrotum.

Dermatofibrosarcoma protuberans is a rare tumor that arises in the dermis, with a strong tendency to recur locally. It is slow growing and often presents as a skin-colored plaque on the trunk, although it may arise anywhere on the body. Dermatofibrosarcoma protuberans has a distinctive histologic appearance, and immunohistochemical studies can help make the diagnosis. This case report describes a young man who presented with complaints of an enlarging right scrotal mass and was diagnosed with dermatofibrosarcoma protuberans.

Outcomes of a pharmacist-driven vancomycin monitoring initiative in a community hospital.

WHAT IS KNOWN AND OBJECTIVE: Vancomycin, an antibiotic commonly used to treat MRSA infections, can be nephrotoxic. Administering vancomycin requires close monitoring of serum vancomycin levels and appropriate dosing based on patients' renal function, underlying infection type and serum concentration levels. This article discusses the results and implications of a pharmacist-driven vancomycin monitoring initiative, which was implemented at Mercy Catholic Medical Center's Philadelphia Campus (MPC) in July 2016. METHODS: MPC pharmacists were trained on how to give appropriate vancomycin dosing recommendations based on patients' vancomycin trough levels, renal function and underlying infection. This retrospective observational study consisted of patients who presented to MPC and were administered vancomycin over a 3-month period in 2015 for pre-implementation cohort and over a 3-month period in 2018 for post-implementation cohort. Patients with age ≥18 and receiving vancomycin for a minimum of 48 hours were included, whereas ESRD patients were excluded. Primary goal evaluated whether the incidence of AKI decreased with the pharmacist-driven initiative. Secondary goal assessed whether vancomycin level monitoring and achievement of goal serum levels improved with the initiative. RESULTS AND DISCUSSION: A total of 214 patients were included in the final data analysis, with 110 patients in the pre-implementation cohort and 104 patients in the post-implementation cohort. Although not statistically significant, a higher incidence of AKI was observed in the post-implementation cohort. However, compared to pre-implementation cohort, post-implementation group had higher percentage of patients with underlying comorbidities (such as CKD), higher number of cases of severe sepsis and septic shock, and greater number of patients with concomitant exposure to CT contrast and piperacillin-tazobactam-all of which were confounding factors that likely increased the AKI incidence in post-implementation cohort. With the initiative, there was a significant increase in the number of patients with appropriate vancomycin trough level monitoring (27.3% vs 55.8%, p value < 0.001) in the post-implementation cohort and a decrease in the number of patients with no trough level monitoring (30% vs. 7.6%, p value < 0.001). WHAT IS NEW AND CONCLUSION: Pharmacist-driven vancomycin monitoring significantly improved the monitoring compliance of vancomycin trough levels. In patients who developed AKI during their hospital course, pharmacist interventions improved the total percentage of patients attaining desired trough goals and helped reduce further renal insult from supratherapeutic vancomycin level. Incorporation of AUC-guided dosing and monitoring has the potential to further optimize vancomycin efficacy and safety.