Beyond post-operative readmissions: analysis of the impact of unplanned readmissions during primary treatment of advanced-stage epithelial ovarian cancer on long-term oncology outcome.

BACKGROUND: Multiple studies have assessed post-operative readmissions in advanced ovarian cancer. OBJECTIVE: To evaluate all unplanned readmissions during the primary treatment period of advanced epithelial ovarian cancer, and the impact of readmission on progression-free survival. METHODS: This was a single institution retrospective study from January 2008 to October 2018. Χ2/Fisher's exact and t-test, or Kruskal-Wallis test were used. Multivariable Cox proportional hazard models were used to assess the effect of covariates in progression-free survival analysis. RESULTS: A total of 484 patients (279 primary cytoreductive surgery, 205 neoadjuvant chemotherapy) were analyzed. In total, 272 of 484 (56%; 37% primary cytoreductive surgery, 32% neoadjuvant chemotherapy, p=0.29) patients were readmitted during the primary treatment period. Overall, 42.3% of the readmissions were surgery related, 47.8% were chemotherapy related, and 59.6% were cancer related but not related to surgery or chemotherapy, and each readmission could qualify for more than one reason. Readmitted patients had a higher rate of chronic kidney disease (4.1% vs 1.0%, p=0.038). Post-operative, chemotherapy, and cancer-related readmissions were similar between the two groups. However, the percentage of inpatient treatment days due to unplanned readmission was twice as high for primary cytoreductive surgery at 2.2% vs 1.3% for neoadjuvant chemotherapy (p<0.001). Despite longer readmissions in the primary cytoreductive surgery group, Cox regression analysis demonstrated that readmissions did not affect progression-free survival (HR=1.22, 95% CI 0.98 to 1.51; p=0.08). Primary cytoreductive surgery, higher modified Frailty Index, grade 3 disease, and optimal cytoreduction were associated with longer progression-free survival. CONCLUSIONS: In this study, 35% of the women with advanced ovarian cancer had at least one unplanned readmission during the entire treatment time. Patients treated by primary cytoreductive surgery spent more days during readmission than those with neoadjuvant chemotherapy. Readmissions did not affect progression-free survival and may not be valuable as a quality metric.

Splenectomy at the time of primary or interval cytoreductive surgery for epithelial ovarian carcinoma: A review of outcomes.

OBJECTIVES: We describe post-operative complications after cytoreductive surgery with and without splenectomy for Stage III or IV epithelial ovarian cancer, and identify areas for quality improvement in post-splenectomy care. METHODS: All patients with ovarian cancer cytoreductive surgery from 2008 to 2018 were identified using an institutional database Gynecologic Oncology Longitudinal Data Collection and Utilization Program (GOLD CUP). We compared patients who had and did not have splenectomy as part of cytoreductive surgery by demographics, comorbidities, stage, operative and post-operative data, readmission rates, progression free survival, overall survival and death from disease. Quality metrics reported include receipt of post-splenectomy education handouts and encapsulated-organism vaccines. Statistical analysis was completed in STATA SE 16.0. RESULTS: We identified 47 patients who underwent splenectomy and 454 who did not during primary or interval cytoreductive surgery. Final stage was IIIB in 1 (2.1%), IIIC in 26 (55.3%), IVA in 7 (14.9%), and IVB in 13 (27.7%) patients. Those with splenectomy had significantly higher stage. Surgery duration and hospital length of stay were longer and blood transfusion more common after splenectomy, but there were no differences in post-operative infection, readmission, or overall survival. Pancreatic leaks were seen in 4/47 (8.5%) patients. Post-splenectomy vaccinations were documented in 42/47 (89.4%) patients. Only 2/47 (4.3%) received post-splenectomy discharge instructions and 3/7 (42.9%) received aspirin for platelets 1 million or more. CONCLUSIONS: While splenectomy adds morbidity, it continues to offer benefit in those patients who can achieve optimal cytoreduction. Areas for quality improvement in post-splenectomy care include receipt of vaccinations, patient discharge information, and timely pancreatic fistula management.

Efficacy and safety of a restrictive blood transfusion protocol in gynecologic surgical patients.

Objectives: This study sought to compare differences in blood transfusion and surgical complication rates before and after the implementation of a restrictive blood transfusion protocol. Methods: On July 1, 2018, our institution implemented a restrictive blood transfusion protocol utilizing a hemoglobin trigger of less than 7 g/dL. Retrospective chart review was completed to review patients undergoing major abdominal surgery by the gynecology and gynecologic oncology services 18 months before, and after initiation of the transfusion protocol. Outcomes included number of patients, units transfused and postoperative complication rates. Complications included reoperation on the day of admission, surgical site infections, wound disruptions, pulmonary, renal, central nervous system, and cardiovascular complications, as well as deep venous thromboses, readmissions, and 30-day mortality. Results: There were 290 people in the pre- and 449 patients in the post-protocol group. A similar number of patients received blood transfusions in both groups (9.3% versus 10.6% p = 0.57). However, significantly fewer units of blood were given post-protocol initiation. For every patient who received a transfusion pre-protocol, 2.66 units were administered compared to 1.2 units after the protocol was initiated (p = 0.003). All postoperative complications were not significantly different between groups (p > 0.05). Individual postoperative complications were combined and analyzed using a clustered approach to detect rates of complications more conservatively. Both the 7-system (5.1% versus 4.9%, p = 0.90) and 8-system (5.5% versus 4.9%, p = 0.72) clustered analyses were not significantly different before and after the initiation of the transfusion protocol. Conclusions: A restrictive transfusion protocol is effective in decreasing the number of units of blood transfused without affecting postoperative complication rates in gynecologic surgery patients.

Barriers to surgical menopause counseling in gynecologic cancers: a quantitative and qualitative study of patients and providers.

OBJECTIVE: The objective of this study is to identify factors associated with receiving surgical menopause counseling in gynecologic cancer patients, as well as patient and provider perspectives, regarding surgical menopause counseling and management. METHODS: We conducted a single-institution mixed-method study combining retrospective chart review and patient and provider surveys. Patients younger than 51 years who experienced surgical menopause after gynecologic cancer treatment from January 2017 to December 2019 were surveyed in April 2021 about experiences with menopause counseling, barriers to care, and quality of life. We then reviewed charts of only patients who fully completed surveys. All gynecologic oncology providers were surveyed about surgical menopause practices. Logistic regression identified factors associated with receiving counseling. RESULTS: Sixty-six of 75 identified met inclusion criteria and received survey invitations. Thirty-five (53%) completed surveys. Sixty percent had documented surgical menopause counseling. Patients who were counseled were younger (43 vs 48.5 years, P = 0.005), more likely to have referrals for menopause care (12 vs 9, P = 0.036), more likely to have menopause providers other than oncology providers (14 vs 8, P = 0.001), and had fewer comorbidities. Decreasing age at surgery increased odds of counseling. Most reported continued menopause symptoms and quality of life disturbances. Half were satisfied with menopause care. Majority preferred counseling from oncology providers. Most providers always counseled on surgical menopause but cited lack of time as the primary obstacle for complete counseling. CONCLUSIONS: Younger age at surgery increased odds of receiving surgical menopause counseling. Gynecologic cancer patients experienced significant menopause-related disturbances. Improved understanding of patient and provider preferences and greater emphases on surgical menopause and survivorship will improve care for gynecologic oncology patients.

Chitosan-Functionalized Graphene Oxide as a Potential Immunoadjuvant.

The application of graphene oxide (GO) as a potential vaccine adjuvant has recently attracted considerable attention. However, appropriate surface functionalization of GO is crucial to improve its biocompatibility and enhance its adjuvant activity. In this study, we developed a simple method to prepare chitosan (CS)-functionalized GO (GO-CS) and further investigated its potential as a nanoadjuvant. Compared with GO, GO-CS possessed considerably smaller size, positive surface charge, and better thermal stability. The functionalization of GO with CS was effective in decreasing the non-specific protein adsorption and improving its biocompatibility. Furthermore, GO-CS significantly activated RAW264.7 cells and stimulated more cytokines for mediating cellular immune response, which was mainly due to the synergistic immunostimulatory effect of both GO and CS. GO-CS exhibits strong potential as a safe nanoadjuvant for vaccines and immunotherapy.

Graphene oxide-chitosan nanocomposites for intracellular delivery of immunostimulatory CpG oligodeoxynucleotides.

CpG oligodeoxynucleotides (ODNs) activate innate and adaptive immune responses, and show strong potential as immunotherapeutic agents against various diseases. Benefiting from their unique physicochemical properties, graphene oxide (GO) has recently attracted great attention in nanomedicine. In this study, we developed a novel CpG ODNs delivery system based on GO-chitosan (GO-CS) nanocomposites. GO-CS nanocomposites were prepared by self-assembly of both components via electrostatic interactions. Compared with GO, GO-CS nanocomposites possessed smaller size, positive surface charge and lower cytotoxicity. CpG ODNs were loaded onto GO-CS nanocomposites via electrostatic interactions. GO-CS nanocomposites greatly improved the loading capacity and cellular uptake of CpG ODNs. GO-CS/CpG ODNs complexes further resulted in an enhanced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production compared with that of free CpG ODNs and GO/CpG ODNs complexes. Therefore, GO-CS nanocomposites can serve as efficient nanocarriers for enhancing the delivery efficiency of CpG ODNs.

Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1-Seropositive Kenyan Men.

INTRODUCTION: HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. METHODS: We analyzed semen samples from 42 HIV-1-seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. RESULTS: Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: -0.77, 95% CI: -1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. CONCLUSION: Most of these HIV-1-infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission.

Folate-conjugated boron nitride nanospheres for targeted delivery of anticancer drugs.

With its unique physical and chemical properties and structural similarity to carbon, boron nitride (BN) has attracted considerable attention and found many applications. Biomedical applications of BN have recently started to emerge, raising great hopes in drug and gene delivery. Here, we developed a targeted anticancer drug delivery system based on folate-conjugated BN nanospheres (BNNS) with receptor-mediated targeting. Folic acid (FA) was successfully grafted onto BNNS via esterification reaction. In vitro cytotoxicity assay showed that BNNS-FA complexes were non-toxic to HeLa cells up to a concentration of 100 µg/mL. Then, doxorubicin hydrochloride (DOX), a commonly used anticancer drug, was loaded onto BNNS-FA complexes. BNNS-FA/DOX complexes were stable at pH 7.4 but effectively released DOX at pH 5.0, which exhibited a pH sensitive and sustained release pattern. BNNS-FA/DOX complexes could be recognized and specifically internalized by HeLa cells via FA receptor-mediated endocytosis. BNNS-FA/DOX complexes exhibited greater cytotoxicity to HeLa cells than free DOX and BNNS/DOX complexes due to the increased cellular uptake of DOX mediated by the FA receptor. Therefore, BNNS-FA complexes had strong potential for targeted cancer therapy.

Impact of rapid influenza PCR testing on hospitalization and antiviral use: A retrospective cohort study.

Rapid PCR-based influenza tests are increasingly used as point-of-care diagnostics in hospitals and clinics. To our knowledge, no prior studies have described clinical outcomes with implementation of rapid PCR-based influenza tests in hospitalized adult inpatients. Electronic medical records were used to assess differences in laboratory testing time and antiviral use among a subset of 175 consecutive adult inpatients tested for influenza in two respiratory seasons before and after implementation of rapid PCR-based influenza testing at an academic medical center. Of the 350 hospitalized inpatients included in this analysis, 96 (27%) were over 65 years of age and 308 (88%) had a comorbid condition. The overall time to result decreased significantly from 25.2 to 1.7 hr (P < 0.001) after implementation of rapid PCR-based influenza testing. Among influenza-negative patients, the frequency of oseltamivir initiation remained unchanged (before: 43% vs. after: 45%; P = 0.60), though the median duration of oseltamivir was significantly decreased from 1.1 to 0.0 days (P < 0.001). By providing an earlier result to clinicians, rapid PCR-based influenza tests may decrease unnecessary antiviral use among adult inpatients who test negative for influenza.