Patient Perspectives on Outpatient versus Inpatient Cervical Ripening for Induction of Labor.

OBJECTIVE: Our objective was to compare patient perceived control and experience with outpatient versus inpatient cervical ripening. STUDY DESIGN: This is a retrospective mixed-methods analysis of a quality improvement initiative focused on the impact to patients of incorporating outpatient cervical ripening into routine practice. Postpartum inpatients who had elected for outpatient cervical ripening (outpatients) and those who met criteria for outpatient cervical ripening but opted for an inpatient setting (inpatients) were invited to participate in the study. Patients completed the Perceived Control in Childbirth Scale, and scores were compared between outpatient and inpatient groups using Mann-Whitney U test. In addition, semistructured questions elicited feedback prior to hospital discharge, and these qualitative data were analyzed using iterative thematic analysis. RESULTS: The study population consisted of 36 outpatients and 38 inpatients. The median score on the Perceived Control in Childbirth Scale was 69 for outpatients and 67 for inpatients (p-value = 0.49), out of a maximum score of 72 (representing the highest level of perceived control). Both groups reported similarly high levels of perceived control, regardless of cervical ripening setting. In the qualitative analysis, pain was the most common theme in both groups. Inpatients reported more distress despite access to stronger pain medications. Outpatients utilized a variety of distraction techniques and expressed gratitude for their setting more than inpatients. CONCLUSION: Outpatient cervical ripening can be a patient-centered solution to obstetric throughput challenges arising from increased numbers of inductions. Those who underwent outpatient cervical ripening had similar perceived control to those who underwent inpatient cervical ripening, suggesting that individual patient preferences are most important in determining the optimal setting for care. The patients' reported experiences identified focus areas for process improvement efforts and future research, including improving patient education regarding expectations and innovating new pain management strategies for cervical ripening. KEY POINTS: · Patient experiences must inform patient-centered care.. · Perceived control with cervical ripening was high.. · Pain with cervical ripening was the most cited theme..

Efficacy of oral and topical antioxidants in the prevention and management of oral mucositis in head and neck cancer patients: a systematic review and meta-analyses.

PURPOSE: To evaluate the effectiveness of antioxidants in the prevention and management of oral mucositis in adults undergoing radiotherapy and/or chemotherapy with diagnosed head and neck cancer (HNC) compared to placebo intervention. METHODS: Cochrane, EMBASE, PubMed, and Web of Science databases were used to search for randomized controlled trials (RCTs) comparing oral or topical antioxidants with placebo in clinically diagnosed HNC adult patients receiving radiotherapy with/without chemotherapy. The primary outcome was to assess the efficacy of the antioxidant to prevent and decrease the incidence/prevalence and severity of oral/oropharyngeal mucositis. The risk of bias was assessed following Cochrane's guidelines. RESULTS: The database search resulted in 203 records up to February 19, 2021. Thirteen RCTs were included with 650 HNC-diagnosed patients. Included studies showed a statistically significant improvement in mucositis severity score for all antioxidants except melatonin. However, further studies are needed as only one study reported outcomes for zinc, propolis, curcumin, and silymarin. Patients receiving vitamin E were 60% less likely to develop severe mucositis grade 2 or higher than those receiving placebo in one study (P = 0.040). Patients receiving zinc were 95% less likely to develop severe mucositis (grades 3-4) in one study compared to placebo (P = 0.031). One meta-analysis showed no statistical difference in the risk of having severe mucositis (grades 3-4) with 199 patients compared to placebo for honey (n = 2 studies, P = 0.403). Meta-analyses could not be conducted for zinc, propolis, curcumin, melatonin, silymarin, and selenium due to the lack of studies reporting similar outcomes for the same intervention. CONCLUSION: Though oral and topical antioxidants significantly improved mucositis severity scores in HNC patients receiving radiotherapy with/without chemotherapy in individual studies, the quality of the evidence was low due to the small number of studies and unclear/high-risk bias. Additionally, large RCTs are needed to confirm these results.

Association of CT findings in patients with hemoperitoneum due to ruptured ovarian cysts with subsequent intervention.

PURPOSE: Hemoperitoneum caused by ovarian cyst rupture may necessitate intervention. The literature is lacking in descriptions of CT findings that help guide patient management. The purpose of this study is to consider CT findings associated with a need for intervention (surgical or interventional radiology management) versus conservative treatment (observation, pain management, and blood transfusions). METHODS: Two radiologists retrospectively and independently reviewed 103 CTs of pre-menopausal women who presented with acute hemoperitoneum related to ruptured ovarian cysts between January 2010 and January 2019. The following imaging features were assessed: ovarian cyst characteristics, sentinel clot, contrast extravasation, and hemoperitoneum size. Findings were correlated with patient demographics, clinical parameters, and management with surgery/interventional radiology procedure (intervention group) versus conservative management (conservative group). RESULTS: Of the 103 patients with hemoperitoneum from cyst rupture, 16% (n = 16) required intervention, and 84% underwent conservative treatment (n = 87). Length of stay (p = .008) was higher in the intervention group. Statistically significant CT findings in the intervention versus conservative group included (p-value reader 1/p-value reader 2) greatest AP dimension of hemoperitoneum (p = .001/p = 0.02), posterior cul-de-sac AP dimension (p = 0.03/p = .006), total cul-de-sac AP dimension (p = .002/p = .007), and number of spaces with hemoperitoneum (p = .01/p = .02). There was good to excellent inter-reader agreement for these findings (ICC 0.68-0.91). Active contrast extravasation was significant for one reader (p = .02) with poor inter-reader agreement (ICC 0.36). In utilizing ROC curves, thresholds of 107 mm (greatest axial AP dimension of hemoperitoneum) yielded a sensitivity and specificity of 0.81 and 0.62 for reader 1 and 0.69 and 0.55 for reader 2; 45 mm (posterior cul-de-sac AP dimension) yielded a sensitivity and specificity of 0.75 and 0.63 for reader 1 and 0.94 and 0.49 for reader 2; 70 mm (total cul-de-sac AP dimension) yielded a sensitivity and specificity of 0.75 and 0.64 for reader 1 and 0.75 and 0.50 for reader 2; and greater than 5 spaces yielded a sensitivity and specificity of 0.75 and 0.58 for reader 1 and 0.69 and 0.70 for reader 2. CONCLUSION: CT findings associated with intervention in hemoperitoneum due to ovarian cyst rupture include size of hemoperitoneum, number of abdominopelvic spaces with hemoperitoneum, and contrast extravasation.

Development of a Machine Learning Model for Sonographic Assessment of Gestational Age.

Importance: Fetal ultrasonography is essential for confirmation of gestational age (GA), and accurate GA assessment is important for providing appropriate care throughout pregnancy and for identifying complications, including fetal growth disorders. Derivation of GA from manual fetal biometry measurements (ie, head, abdomen, and femur) is operator dependent and time-consuming. Objective: To develop artificial intelligence (AI) models to estimate GA with higher accuracy and reliability, leveraging standard biometry images and fly-to ultrasonography videos. Design, Setting, and Participants: To improve GA estimates, this diagnostic study used AI to interpret standard plane ultrasonography images and fly-to ultrasonography videos, which are 5- to 10-second videos that can be automatically recorded as part of the standard of care before the still image is captured. Three AI models were developed and validated: (1) an image model using standard plane images, (2) a video model using fly-to videos, and (3) an ensemble model (combining both image and video models). The models were trained and evaluated on data from the Fetal Age Machine Learning Initiative (FAMLI) cohort, which included participants from 2 study sites at Chapel Hill, North Carolina (US), and Lusaka, Zambia. Participants were eligible to be part of this study if they received routine antenatal care at 1 of these sites, were aged 18 years or older, had a viable intrauterine singleton pregnancy, and could provide written consent. They were not eligible if they had known uterine or fetal abnormality, or had any other conditions that would make participation unsafe or complicate interpretation. Data analysis was performed from January to July 2022. Main Outcomes and Measures: The primary analysis outcome for GA was the mean difference in absolute error between the GA model estimate and the clinical standard estimate, with the ground truth GA extrapolated from the initial GA estimated at an initial examination. Results: Of the total cohort of 3842 participants, data were calculated for a test set of 404 participants with a mean (SD) age of 28.8 (5.6) years at enrollment. All models were statistically superior to standard fetal biometry-based GA estimates derived from images captured by expert sonographers. The ensemble model had the lowest mean absolute error compared with the clinical standard fetal biometry (mean [SD] difference, -1.51 [3.96] days; 95% CI, -1.90 to -1.10 days). All 3 models outperformed standard biometry by a more substantial margin on fetuses that were predicted to be small for their GA. Conclusions and Relevance: These findings suggest that AI models have the potential to empower trained operators to estimate GA with higher accuracy.

Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Checkpoint inhibitors targeting programmed death receptor-1 (PD-1) have been tested in the neoadjuvant setting for the treatment of locoregionally advanced head and neck squamous cell carcinoma (HNSCC); however, response rates are modest. We hypothesized that adding stereotactic body radiation therapy (SBRT) to anti-PD-1 would be safe prior to definitive surgical resection and would enhance pathological response compared with historical cohorts of patients with locoregionally advanced HNSCC treated with checkpoint inhibitor alone. METHODS: The Neoadjuvant Immuno-Radiotherapy Trial was an investigator-initiated single institution phase Ib clinical trial that enrolled patients with previously untreated locally advanced HPV-positive and HPV-negative HNSCC between 2018 and 2019. Eligible patients were treated with neoadjuvant SBRT at a total dose of either 40 Gy in 5 fractions or 24 Gy in 3 fractions, delivered in a 1-week timespan, with or without nivolumab, prior to definitive surgical resection. Patients were then planned for treatment with adjuvant nivolumab for 3 months. The primary safety endpoint was unplanned delay in surgery considered to be at least possibly related to neoadjuvant treatment. The primary efficacy endpoints included pathological complete response (pCR), major pathological response (mPR), and the rate of clinical to pathological downstaging after neoadjuvant treatment. RESULTS: Twenty-one patients underwent neoadjuvant treatment, which was well tolerated and did not delay surgery, thus meeting the primary endpoint. Tissue responses were characterized by robust inflammatory infiltrates in the regression bed, plasma cells and cholesterol clefts. Among the entire study group, the mPR and pCR rate was 86% and 67%, respectively. Clinical to pathological downstaging occurred in 90% of the patients treated. CONCLUSION: These data demonstrate that radiation delivered only to the gross tumor volume combined with immunotherapy was safe, resulted in a high rate of mPR and should be further evaluated as a locally focused neoadjuvant therapy for patients with head and neck cancer. TRIAL REGISTRATION NUMBER: This study is registered with clinicaltrials.gov (NCT03247712) and is active, but closed to patient accrual.

Transoral robotic surgery and neck dissection for HPV-positive oropharyngeal carcinoma: Importance of nodal count in survival.

BACKGROUND: In this study we determine the survival in patients with HPV-positive oropharyngeal carcinoma treated with transoral robotic surgery (TORS), neck dissection and risk-adapted adjuvant therapy. METHODS: We retrospectively identified 122 patients with HPV-positive oropharyngeal carcinoma treated with TORS and neck dissection between 2011 and 2018. Survival probability was calculated. We determined the effect of the type of neck dissection performed (modified radical neck dissection-MRND vs. selective neck dissection - SND), extranodal extension (ENE), margin status, and presence of ≥ 5 metastatic nodes on survival. RESULTS: Our patient population had a five-year overall survival of 91.0% (95% C.I. 85-97%). The five-year probability of recurrence or cancer-associated death was 0.0977 (95% C.I. 0.0927-0.1027). The five-year probability of cancer-associated death was 0.0528 (95% C.I. 0.048-0.0570). All patients who died of their disease had distant metastasis. Our PEG dependence rate was 0%. Patients with ENE and positive margins who underwent adjuvant chemoradiation did not have worse survival. Presence of ≥ 5 metastatic nodes portended worse survival after controlling for age, positive ENE and margins. Low yield (<18 nodes) on neck dissection worsened DFS on multivariable analysis. Furthermore, patients who underwent SND did not have worse OS than those who underwent MRND. CONCLUSION: Our study demonstrates that surgery could be simplified by performing TORS with SND rather than MRND. The one true poor prognostic factor in HPV-positive oropharyngeal carcinoma patients who undergo surgery is high nodal burden. Patients with high nodal burden are much more likely to die from their disease.

Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer.

INTRODUCTION: We have shown previously that treatment with pegylated leptin peptide receptor antagonist 2 (PEG-LPrA2) reduced the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor type 2 (VEGFR2) and growth of 4T1-breast cancer (BC) in syngeneic mice. In this investigation, PEG-LPrA2 was used to evaluate whether the inhibition of leptin signaling has differential impact on the expression of pro-angiogenic and pro-proliferative molecules and growth of human estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) BC xenografts hosted by immunodeficient mice. METHODS: To test the contribution of leptin signaling to BC growth and expression of leptin-targeted molecules, PEG-LPrA2 treatment was applied to severe immunodeficient mice hosting established ER+ (MCF-7 cells; ovariectomized/supplemented with estradiol) and ER- (MDA-MB231 cells) BC xenografts. To further assess leptin and PEG-LPrA2 effects on ER+ and ER- BC, the expression of VEGF and VEGFR2 (protein and mRNA) was investigated in cell cultures. RESULTS: PEG-LPrA2 more effectively reduced the growth of ER+ (>40-fold) than ER- BC (twofold) and expression of pro-angiogenic (VEGF/VEGFR2, leptin/leptin receptor OB-R, and IL-1 receptor type I) and pro-proliferative molecules (proliferating cell nuclear antigen and cyclin D1) in ER+ than in ER- BC. Mouse tumor stroma in ER+ BC expressed high levels of VEGF and leptin that was induced by leptin signaling. Leptin upregulated the transcriptional expression of VEGF/VEGFR2 in MCF-7 and MDA-MB231 cells. CONCLUSIONS: These results suggest that leptin signaling plays an important role in the growth of both ER+ and ER- BC that is associated with the leptin regulation of pro-angiogenic and pro-proliferative molecules. These data provide support for the potential use of leptin-signaling inhibition as a novel treatment for ER+ and ER- BC.

Prevalence of trismus in patients with head and neck cancer: A systematic review with meta-analysis.

BACKGROUND: The purpose of this systematic review and meta-analysis was to determine the prevalence of trismus in patients with head and neck cancer. METHODS: Four electronic databases were searched: Cochrane Library, MEDLINE, EMBASE, and Web of Science up to April 2018. Level of evidence was assessed based on Oxford Centre for Evidence-based Medicine. Publications were restricted to prospective cohort studies (n = 15), randomized clinical trials (n = 3), and cross-sectional studies (n = 5) reporting on trismus as mouth maximum opening less than or equal to 35 mm in the English language. RESULTS: A total of 636 abstracts were reviewed for inclusion. Twenty-three studies were included in qualitative analysis and 15 studies in meta-analysis. The results included 2786 patients with head and neck cancer treated with surgery, radiotherapy, and/or chemotherapy either alone or in combination. Based on meta-analyses, the weighted average prevalence of trismus increased from 17.3% at baseline (95% confidence interval [CI], 10.8%-26.5%) to a peak of 44.1% at 6 months (95% CI, 36.7%-51.8%) and decreased to 32.1% at 12 months (95% CI, 27.2%-37.4%) and continued in average 32.6% at 3-10 years (95% CI, 22.0%-45.3%). CONCLUSIONS: Having a primary site of the oral cavity or oropharynx was associated with a higher risk for developing trismus based on individual studies. Prospective cohort studies or randomized controlled trials with multiple objective trismus measurements, evaluation of disease characteristics, and treatment variables are needed to further investigate the prevalence of trismus secondary to head and neck cancer treatment.

Incorporating Experiential Learning Techniques to Improve Self-Efficacy in Clinical Special Care Dentistry Education.

The New York University College of Dentistry has introduced a clinical rotation for fourth-year dental students that focuses on treating people with special health care needs (PSN). The aim of this study was to investigate the hypothesis that clinical experience in treating patients with special health care needs during predoctoral education is associated with increased self-assessed student ability and comfort and therefore self-efficacy. The study also investigated whether other characteristics, such as prior personal or volunteer experience with this population, service-mindedness, and/or the inclination to treat underserved populations, were associated with comfort in treating PSN. A survey was used to assess changes in students' perceived knowledge, beliefs, and attitudes regarding treating PSN before and after the clinical experience for July 2012-June 2013. The survey included questions about students' service-mindedness, comfort, perceptions of abilities of PSN and educational importance of learning to treat PSN, desire for clinical experience, and future intent or interest in treating PSN. Out of 364 students invited to participate, 127 surveys were returned, for a response rate of 34.9%. The results showed statistically significant increases on six items following training: impressions about the importance of oral health among PSN, comfort in treating people with cognitive disabilities and with medical complexities, intent to treat PSN in future practice, interest in including PSN in postgraduate training, and belief that PSN could be treated in the private practice setting. These students reported preferring to learn in the clinical setting over didactic instruction. This clinical experience was associated with improved self-efficacy in treating PSN and increased intentions to treat this population in future practice. Improvements were particularly evident among those with the least prior experience with PSN and were independent of other aspects of the students' past experience, future goals, or personality characteristics.

Intravenous bisphosphonate-related osteonecrosis of the jaw: long-term follow-up of 109 patients.

OBJECTIVE: We report long-term follow-up of patients with intravenous bisphosphonate-related osteonecrosis of the jaw (BRONJ). STUDY DESIGN: Medical and dental histories, including type and duration of bisphosphonate treatment and comorbidities, were analyzed and compared with clinical course of 109 patients with BRONJ at Memorial Sloan-Kettering Cancer Center Dental Service. RESULTS: Median onset of BRONJ in months was 21 (zoledronic acid), 30 (pamidronate), and 36 (pamidronate plus zoledronic acid), with a significant difference between the pamidronate plus zoledronic acid and zoledronic acid groups (P = .01; Kruskal-Wallis). The median number of doses for BRONJ onset was significantly less with zoledronic acid (n = 18) than pamidronte plus zoledronic acid (n = 36; P = .001), but not pamidronate alone (n = 29). An association between diabetes (P = .05), decayed-missing-filled teeth (P = .02), and smoking (P = .03) and progression of BRONJ was identified through χ(2) test. CONCLUSIONS: This long-term follow-up of BRONJ cases enhances the literature and contributes to the knowledge of BRONJ clinical course.

Leptin upregulates VEGF in breast cancer via canonic and non-canonical signalling pathways and NFkappaB/HIF-1alpha activation.

High levels of VEGF and leptin are strongly linked to worse prognosis of breast cancer. Leptin signalling upregulates VEGF in human and mouse mammary tumor cells (MT), but the specific molecular mechanisms are largely unknown. Pharmacologic and genetic approaches were used to dissect the mechanism of leptin regulation of VEGF protein and mRNA in MT (4T1, EMT6 and MMT). A series of VEGF-promoter Luc-reporters (full-length and transcription factor-binding deletions) were transfected into MT to analyze leptin regulation of VEGF transcription. Deletion analysis of VEGF promoter and RNA knockdown shows that HIF-1alpha and NFkappaB are essentials for leptin regulation of VEGF. Leptin activation of HIF-1alpha was mainly linked to canonic (MAPK, PI-3K) and non-canonic (PKC, JNK and p38 MAP) signalling pathways. Leptin non-canonic signalling pathways (JNK, p38 MAP and to less extent PKC) were linked to NFkappaB activation. SP1 was involved in leptin regulation of VEGF in 4T1 cells. AP1 was not involved and AP2 repressed leptin-induced increase of VEGF. Overall, these data suggest that leptin signalling regulates VEGF mainly through HIF-1alpha and NFkappaB. These results delineate a comprehensive mechanism for leptin regulation of VEGF in MT. Disruption of leptin signalling could be used as a novel way to treat breast cancer.