Recurrence In High-risk Patients Research Articles

Microbiota restoration for recurrent Clostridioides difficile infection.

Since the publication of the recent North American and European guidelines on management of Clostridioides difficile infection (CDI), new evidence describing the epidemiology, testing and treatment of CDI has emerged. Despite all advances in infection control and antibiotic stewardship, the incidence and burden of CDI in the hospitals and the community remains at a stable high. Coupled with the incidence of primary CDI, there is a stable high incidence of recurrent CDI. Testing for primary and recurrent CDI remains a clinical challenge owing to high sensitivity of the PCR (leading to false positives) and somewhat limited sensitivity of EIA for toxin. The pathophysiology of recurrent CDI involves an ongoing disruption of the microbiota owing to the infection and the treatment of CDI employed. Broad spectrum antibiotics such as vancomycin leads to further disruption of microbiota compared to fidaxomicin which has a lower disruption of the microbiota and leads to fewer recurrences. Owing to these data fidaxomicin is considered as the first line antibiotic for recurrent CDI. Intravenous bezlotoxumab is a monoclonal antibody that reduces the risk of recurrence in high-risk patients but does not restore the microbiota. Experimental fecal microbiota transplantation (FMT) has been available for more than a decade. Owing to the success of FMT, two new non-invasive donor dependent Food and Drug Administration (FDA) approved therapies have been available since late 2022. This review summarizes all these conundrums regarding CDI and provides clinical pearls to use in day-to-day practice.

Integrated Safety and Efficacy Analyses of Phase3 Trials of a Microbiome Therapeutic for Recurrent CDI.

Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI. To evaluate safety and efficacy of VOS from two phase3 trials, (randomized, placebo-controlled [ECOSPORIII: NCT03183128] and open-label, single arm [ECOSPORIV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities. VOS or placebo [ECOSPORIII only] (4 capsules once daily for 3days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week8; serious TEAEs and TEAEs of special interest collected through week24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks8 and 24. TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week8 was 9.5% (95%CI 6.6-13.0) and remained low through 24weeks (15.2%; 95%CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression. VOS was well tolerated and rates of rCDI remained low through week24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients. ClinicalTrials.gov identifier, NCT03183128 and NCT03183141.

Embolization of the middle meningeal artery for the prevention of chronic subdural hematoma recurrence in high-risk patients: a randomized controlled trial—the EMPROTECT study protocol

BackgroundMiddle meningeal artery (MMA) embolization has been proposed as a treatment of chronic subdural hematoma (CSDH). The benefit of the procedure has yet to be demonstrated in a randomized controlled...

The association between perioperative opioids and breast cancer recurrence: a narrative review of the literature.

Opioid use disorder is an evolving crisis, and 17.2% of postsurgical patients continue to fill an opioid prescription one year after surgery. Preclinical studies suggest perioperative opioid use, defined here as opioids used in the setting of operative pain, may be linked to inferior oncologic outcomes. If this were true, opioid minimization strategies for surgical patients may reduce opioid-related deaths in more than one way. This review aims to describe the association between perioperative opioid use and breast cancer recurrence. On November 1, 2021, we searched the Ovid and EMBASE databases for the terms "breast neoplasm", "opioid analgesics", "neoplasm recurrence", and "neoplasm metastasis". Of the 350 articles retrieved, 11 met our inclusion criteria. The review was undertaken using the enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) checklist for quality. Clinical studies report no clear association between perioperative opioid use and local or distant breast cancer recurrence. Mixed results were found when assessing perioperative opioid use and overall survival. Multiple studies paradoxically found opioid use to be associated with lower recurrence rates, despite higher mortality rates. Most studies showed no difference in recurrence or survival in breast cancer surgery patients who did or did not receive opioid-containing analgesia, although most findings were limited by study design and low event rates in patients with breast cancer. The lack of a clear connection between perioperative opioid use and breast cancer recurrence contradicts some preclinical data, which describes mechanisms through which opioids upregulate tumor proliferation which might worsen oncologic outcomes. Existing clinical literature is limited to mostly retrospective studies in patients with predominantly early-stage breast cancers, with low event rates. Given the worsening opioid epidemic and preclinical study findings, opioid minimization strategies should still be explored. Future work should be prospective and examine cancer recurrence in high-risk patients with more advanced tumor pathologies.

Prognostic value of PD-L1 expression in recurrent renal cell carcinoma after nephrectomy: a secondary analysis of the ARCHERY study

BackgroundNephrectomy is a curative treatment for localized renal cell carcinoma (RCC), but patients with poor prognostic features may experience relapse. Understanding the prognostic impact of programmed death-ligand 1 (PD-L1) expression in patients who underwent nephrectomy for RCC may aid in future development of adjuvant therapy.MethodsOf 770 surgical specimens collected from Japanese patients enrolled in the ARCHERY study, only samples obtained from patients with recurrent RCC after nephrectomy were examined for this secondary analysis. Patients were categorized into low- and high-risk groups based on clinical stage and Fuhrman grade. Time to recurrence (TTR) and overall survival (OS) were analyzed.ResultsBoth TTR and OS were shorter in patients with PD-L1-positive than -negative tumors (median TTR 12.1 vs. 21.9 months [HR 1.46, 95% CI 1.17, 1.81]; median OS, 75.8 vs. 97.7 months [HR 1.32, 95% CI 1.00, 1.75]). TTR and OS were shorter in high-risk patients with PD-L1-positive than -negative tumors (median TTR 7.6 vs. 15.3 months [HR 1.49, 95% CI 1.11, 2.00]; median OS, 55.2 vs. 83.5 months [HR 1.53, 95% CI 1.06, 2.21]) but not in low-risk patients.ConclusionsThis ARCHERY secondary analysis suggests that PD-L1 expression may play a role in predicting OS and risk of recurrence in high-risk patients with localized RCC.Clinical Trial Registration: UMIN000034131.

Limb-sparing surgery with latissimus dorsi flap reconstruction in extremity soft tissue sarcoma: Case series.

Introduction and importanceFunction-preserving and Limb-sparing surgery are now the accepted gold standard of care for Extremity Soft Tissue Sarcoma (ESTS) with the goal of surgery for STS of extremities to obtain local tumor control and minimal morbidity. Limb-sparing surgery with post-operative radiotherapy for STS results in high survival rates and local control. Adjuvant radio chemotherapy might improve distant and local recurrence in high-risk patients. Hence, we aim to present how to achieve local tumor control and minimal morbidity for high grade ESTS by conducting limb-sparing surgery combined with appropriate reconstruction and radio chemotherapy.Case presentationWe present 2 cases with high grade sarcoma that underwent limb-sparing surgery with Latissimus Dorsi (LD) flap reconstructions. Wide excisions were completed with limb-sparing surgeries for both cases with free surgical margins and LD flap reconstructions. There was no post-operative complication. Follow up examination revealed normal function of the arm. The first patient was still in remission after 2-years follow up. The second patient got pulmonary metastasis after complete resection and adjuvant radiotherapy.Clinical discussionLimb-sparing surgery with LD flap reconstruction is able to remove the tumor completely with negative margin for the primary objective. Secondary objectives are minimizing the morbidity, maximizing postoperative body functions, as well as achieving the best cosmetic value are also achieved. LD flap is commonly easy to harvest and able to give large tissue coverage for reconstruction after surgery.ConclusionLimb sparing surgery followed by soft-tissue reconstruction and radio chemotherapy are suitable for increasing oncologic outcome, tumor control, and limb preservation. However, inhibitions towards local recurrence and distant metastases were not guaranteed.

Adjuvant radiotherapy in malignant tumors of parotid. Experience of the Navarra Hospital Complex.

BackgroundThe objective of the study was to review the outcome of patients with parotid cancer treated with postoperative radiotherapy at Complejo Hospitalario de Navarra in the last ten years.Materials and methodsWe retrospectively reviewed patients treated with adjuvant radiotherapy between January 2008 and December 2018. We analyzed demographic data, histopathologic findings, local control (LC) and overall survival (OS).ResultsA total of 40 patients received postoperative radiotherapy during the period mentioned. There were 22 men (55%) and 18 women (45%). Median age was 58 years (19–90). By tumor histology, the most common was squamous cell carcinoma (22.5%) followed by ex-pleomorphic adenoma (15%) and adenoid cystic carcinoma (10%). According to Surgery, 19 patients (47.5%) underwent a total parotidectomy, 20 (50%) partial parotidectomy, and 1 (2.5%) a radical parotidectomy. Twenty-one patients (51.2%) underwent cervical dissection, most of them being supraomohyoid (31.7%). Reasons for adjuvant RT were: R1 resection (35% of the patients), high grade tumors (27.5%) and 17.5% because R1 surgery and R1. Radiation was administered using IMRT in most patients to a total dose of 60 Gy in 30 fractions. The 5-year overall survival (OS) (Kaplan-Meier) was 81% (95% CI: 68.5–96.2%), and 10-years — 64%. The 5-year local control (LC) (Kaplan-Meier) was 82.4% (95% CI: 91.46–73.33%) and the 10-year LC — 72.2% (95% CI: 54.9–96%). To date, only 4 patients (10%) have died due to their parotid tumor.ConclusionThe adjuvant radiotherapy added to surgery, significantly reduces the risk of recurrence in high-risk patients with a very acceptable survival rate.

Radiotherapy for prevention or management of gynecomastia recurrence: Future role for general gynecomastia patients in plastic surgery given current role in management of high-risk prostate cancer patients on anti-androgenic therapy

Several technologies and innovative approaches continue to emerge for the optimal management of gynecomastia by plastic surgeons; the present study investigates the role of radiation therapy in this context. A systematic review was performed to evaluate the utility of radiotherapy for the prevention and treatment of gynecomastia incidence or recurrence by plastic surgeons. Fifteen articles met the inclusion criteria for review. The mean incidence of gynecomastia was 70% in the high-risk population examined representing prostate cancer patients on estrogen or anti-androgen therapy. Radiotherapy was shown to significantly reduce the incidence to a median of 23%, with all six randomized control studies assessed demonstrating a statistically significant decrease in incidence following radiotherapy prophylaxis. Doses examined ranged from 8 to 16 Gy, delivered between 1 and 11 fractions. Complications following radiotherapy were minor and self-limiting in all cases, restricted to minor skin reactions, and associated with larger radiotherapy doses delivered in fewer fractions. The median complication rate was 12.4% with no major complications, such as neoplastic, pulmonary, or adverse cardiac outcomes. While the efficacy of radiation therapy as a treatment modality for gynecomastia was also established, it was shown to be less effective than other available options. Low-dose radiotherapy to the male breast might be a safe and effective strategy to prevent gynecomastia incidence or recurrence in high-risk patients; further studies are indicated within the common gynecomastia population managed by plastic surgeons to assess the clinical and economical utility of this intervention before a recommendation for its ubiquitous adoption in plastic surgery can be made to continue improving outcomes for high-risk gynecomastia patients.

Rates of Ipsilateral Local-regional Recurrence in High-risk Patients Undergoing Immediate Post-mastectomy Reconstruction (AFT-01)

BackgroundSome surgeons remain hesitant to perform immediate breast reconstruction (IBR) in patients with higher risk cancers owing to concerns about cancer recurrence and/or detection. Our objective was to determine the rate of ipsilateral local-regional recurrence for stage II/III patients who underwent IBR. MethodsThe National Cancer Database special study mechanism was used to create a stratified sample of women diagnosed with stage II/III breast cancer from 1217 facilities. Demographic, tumor, and recurrence data for women who underwent mastectomy with or without IBR were abstracted, including location of recurrence and method of detection. Estimates of 5-year local-regional recurrence rates were calculated and factors associated with recurrence were identified with multivariable Cox regression. ResultsSome 13% (692/5318) of stage II/III patients underwent IBR after mastectomy. Patients undergoing IBR were younger (P < .001), with fewer comorbid conditions (P < .001), and with lower tumor burden in the breast (P = .001) and the lymph nodes (P = 0.01). The 5-year rate of ipsilateral local-regional recurrence was 3.6% with no significant difference between patients with or without IBR (3.0% vs. 3.7%, P = .4). Most recurrences were detected by the patient (45%) or on physician examination (24%). Reconstruction was not associated with recurrence on multivariable analysis (hazard ratio = 0.83, P = .52). ConclusionWomen with stage II/III breast cancer selected for IBR had similar rates of ipsilateral local-regional recurrence compared with those undergoing mastectomy alone. Offering IBR after mastectomy in a patient-centered manner to select patients with stage II/III breast cancer is an acceptable consideration.

Impact of patient's clinical features on the recurring lung metastases of breast cancer

Aim: The aim of this study was to investigate the clinical features affecting on the recurrence of lung metastases of breast cancer.Materials and Methods: Data of 92 patients who had undergone pulmonary metastasectomy of breast cancer were examined interms of recurrence, age, type of primary breast cancer, disease free interval (DFI), PET/CT findings, side of metastasectomy andnumber of resected lung metastases.Results: Solitary and unilateral pulmonary metastases presenting lower SUV following longer period of DFI were less involved inrecurrence whereas invasive lobular and inflammatory carcinomas were more inclined to develop relapsing lung metastases. Agewas not a risk factor for recurrence.Conclusion: Identifying high risk patients for recurrence contributes to prevention of repeating and excessive surgeries.

Early salvage versus adjuvant therapy for treatment of prostate cancer following prostatectomy

The prospective adaptive meta-analysis by the ARTISTIC collaboration did not demonstrate that adjuvant radiotherapy following radical prostatectomy improves event-free survival over early salvage radiotherapy. Early salvage is preferred over adjuvant...

Dose dense chemotherapy might be the only modifiable factor associated with distant recurrence in high-risk patients with endometrial cancer

Dose dense chemotherapy might be the only modifiable factor associated with distant recurrence in high-risk patients with endometrial cancer

Overestimation of Late Distant Recurrences in High-Risk Patients With ER-Positive Breast Cancer: Validity and Accuracy of the CTS5 Risk Score in the TEAM and IDEAL Trials.

Most distant recurrences (DRs) in women with hormone receptor-positive breast cancer occur after 5 years from diagnosis. The Clinical Treatment Score post-5 years (CTS5) estimates DRs after 5 years of adjuvant endocrine therapy (AET). The aim of this study was to externally validate the CTS5 as a prognostic/predictive tool. The CTS5 categorizes patients who have been disease free for 5 years into low, intermediate, and high risk and calculates an absolute risk for developing DRs between 5 and 10 years. Discrimination and calibration were assessed using data from the TEAM and IDEAL trials. The predictive value of the CTS5 was tested with data from the IDEAL trial. A total of 5,895 patients from the TEAM trial and 1,591 patients from the IDEAL trial were included. When assessing the CTS5 discrimination, significantly more DRs were found at 10 years after diagnosis in the CTS5 high- and intermediate-risk groups than in the low-risk group (hazard ratio, 5.7 [95% CI, 3.6 to 8.8] and 2.8 [95% CI, 1.7 to 4.4], respectively). In low- and intermediate-risk patients, the CTS5-predicted DR rates were higher, although not statistically significantly so, than observed rates. However, in high-risk patients, the CTS5-predicted DR rates were significantly higher than observed rates (29% v 19%, respectively; P < .001). The CTS5 was not predictive for extended AET duration. The CTS5 score as applied to patients treated in the TEAM and IDEAL cohorts discriminates between risk categories but overestimates the risk of late DRs in high-risk patients. Therefore, the numerical risk assessment from the CTS5 calculator in its current form should be interpreted with caution when used in daily clinical practice, particularly in high-risk patients.

Abstract P5-12-11: Measuring ovarian escape in pre-menopausal breast cancer patients on ovarian suppression therapy

Abstract Introduction The results of the SOFT and TEXT trials created a paradigm shift in the management of pre-menopausal women with estrogen (ER) or progesterone (PR) receptor positive breast cancer. With findings demonstrating reduced recurrence in high risk patients, the American Society of Clinical Oncology (ASCO) recommended that many in this patient population should receive ovarian suppression (OS) with adjuvant endocrine therapy. However, ancillary analysis of the SOFT trial noted a population of patients with persistently elevated estradiol levels. The clinical significance of this is unknown. The aim of this study was to assess pre-menopausal patients with ER positive breast cancer, in a “real world” clinical setting, who did not achieve maximal estradiol suppression within 3 months, and to evaluate potential contributing risk factors. Methods/Materials This was a single institutional, retrospective, observational study, from February 1, 2010 to January 9, 2018, that evaluated pre-menopausal women receiving adjuvant endocrine therapy with OS (either leuprolide or goserelin). Patients were included if they were receiving adjuvant ovarian suppression with goserelin or leuprolide, had stage I-III ER or PR positive breast cancer, and had at least one estradiol value checked within the first 3 months. The primary objective was to measure the percentage of women with ovarian escape, defined as estradiol level &amp;gt;2.7 pg/mL within 3 months of initiation of OS therapy if on AI therapy, and &amp;gt;21 pg/mL for those patients on tamoxifen. The secondary aim was to associate baseline clinical data (age, body mass index (BMI), and previous receipt of chemotherapy) with higher probability of ovarian escape. Results Between February 1, 2010 and January 9, 2018, 46 patients met inclusion criteria. There were 20 (43.5%) women on tamoxifen and 26 (56.5%) women on an aromatase inhibitor. In the first 3 months, 12 (26.0%) patients failed to achieve maximal OS. Eleven of these continued on OS therapy and 4 (36.3%) did not achieve OS at 6 months. Of these 4 patients who did not achieve ovarian suppression by 6 months, 3 women continued for a total of 12 months, and none of them achieved OS, yielding 6.5% of the total 46 patients who did not achieve ovarian suppression within 1 year. Age was significantly associated with risk of ovarian escape, with older patients (43.0±6.6 years) much more likely to achieve OS within 3 months, compared to younger women (38.5±6.7) (p = 0.037). This difference remained significant in multi-variate analysis. In contrast, BMI, previous chemotherapy, and drug used (leuprolide vs. goserelin) were not significantly associated with likelihood of achieving ovarian suppression. Conclusion It is not uncommon for premenopausal women to have elevated estradiol levels within the first 3 months of ovarian suppression therapy. In this “real world” clinical setting, approximately 1 in 4 women were not maximally suppressed within 3 months. Of these women who did not achieve ovarian suppression in the first 3 months, a quarter of them were also not able to achieve ovarian suppression in the first year. Young age was the most significant risk factor for ovarian escape. Given the relatively high frequency of this phenomenon, larger future studies should evaluate whether ovarian escape in young, pre-menopausal women may be associated with higher recurrence risk, and thus warrant closer monitoring of hormone levels. Table 1: Baseline characteristics by ovarian suppressionAchieved ovarian suppression within 3 monthsp-valueNo (n=11)Yes (n=35)Age38.5±6.743.0±6.60.037BMI29.0±7.627.5±6.50.677Previous Chemotherapy6 (54.6%)21 (60%)1.0Drug0.768Anastrozole3 (27.3%)11 (31.4)Exemestane0 (0%)4 (11.4)Letrozole3 (27.3%)5 (14.3)Tamoxifen5 (45.5%)15 (42.3) Citation Format: Ethan Burns, Susan Xu, Edward McLean, Rosetta Lee, Tejal Patel, Jenny Chang, Polly Niravath. Measuring ovarian escape in pre-menopausal breast cancer patients on ovarian suppression therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-11.

Enfermedad ulcerosa péptica

Peptic ulcer is a mucosal break of diameter 5mm or larger, reaching submucosal layer. H. pylori and non-steroidal anti-inflammatory drugs (NSAID) intake, are the main causes. Their incidence has fallen during last years, in parallel with the incidence of H. pylori and the improvement in the knowledge of NSAID's effects. Symptoms are unspecific. Predominant symptom is epigastric pain, however asymptomatic cases are possible and may appear like a complication of another disorder. Nowadays, diagnosis is mainly endoscopic, allowing both ulcer visualization and to take biopsy samples in order to discard H. pylori and malignancy. Digestive hemorrhage is the most frequent complication, its treatment requires: adequate staging, fluid management, proton pump inhibitors (PPIs) use and endoscopic therapy in ulcer recurrence in high-risk patients. Gastric-wall perforation and obstruction are other possible complications. The two pillars of peptic ulcer treatment are H. pylori eradication therapy and PPI treatment when necessary, according with ulcer location and etiology.

Association of p53, VEGF and Microvascular Density in Colorectal Carcinoma

Introduction: Colorectal Cancer (CRC) is third most common malignancy worldwide. Various genomic alterations play fundamental role in initiation and progression of CRC. Among these, p53 mutation has a crucial role in survival and metastasis and its point mutation induces Vascular Endothelial Growth Factor (VEGF) promoting vascular permeability, migration and differentiation. The degree of angiogenesis can be measured by Microvascular Density (MVD) using CD34, which is helpful in identifying high risk patients for recurrence and metastasis. Aim: The aim of the study was to analyse the expression of p53, VEGF and MVD in CRC and their association with clinicopathological parameters. Materials and Methods: The ambispective study of 2 year duration was conducted from September 2015 to July 2017 in the Department of Pathology, Kalinga Institute of Medical Sciences and PBMH, Bhubaneswar. It included CRC resection specimens and archival tissue blocks. Tissue microarray blocks were prepared manually for IHC application in total 70 cases (58 (82.9%) adenocarcinomas and 12 (17.1%) adenomas) which were histologically staged and graded as per American Joint Committee on Cancer (AJCC) and World Health Organisation (WHO) guidelines. Pearson chi-square test and fisher’s-exact method were used to find significance of p53, VEGF and CD34 expression in adenomas and adenocarcinomas with respect to clinicopathological parameters. Results: No significant statistical association was found between p53, VEGF and MVD with tumour grade and nodal status. Majority, 41 (70.69%) cases were hypervascular (MVD-High). Adenomas 9 (75%) cases, were mostly hypovascular (MVD-Low) with p-value of 0.003. There was significant statistical association between VEGF and MVD with a p-value of 0.01. VEGF and MVD were more expressed on left-sided colon cancers. There was significant statistical association (p=0.01) between p53 graded expression and diagnosis in the present study. MVD and tumour nodal status had an inversely significant relationship (p=0.03). Conclusion: p53 and VEGF expressed more on carcinomas than adenomas. Both p53 and VEGF induce angiogenesis which can be effectively measured by CD34 expression (MVD). There is a directly proportional relationship of angiogenesis and malignant transformation. So these three IHC markers together can be considered a significant prognostic factor involved in CRC.

Extended-Duration Low-Dose Apixaban to Prevent Recurrence in High-Risk Patients With Provoked Venous Thromboembolism

Extended-Duration Low-Dose Apixaban to Prevent Recurrence in High-Risk Patients With Provoked Venous Thromboembolism

2415. Oral Vancomycin for Secondary Prophylaxis of Clostridium difficile Infections among High-risk Patients

Background Clostridium difficile infection (CDI) is associated with high rates of recurrence, and major risk factors for recurrence include prior CDI episode(s) and antibiotic exposure. Prior studies concluded a reduction in CDI recurrence using oral vancomycin for prophylaxis (ppx), but were limited by prescriber bias and inclusion of all hospitalized adult patients with prior CDI and receipt of systemic antibiotics. We sought to determine whether or not oral vancomycin prophylaxis reduced CDI recurrence in high-risk patients.MethodsThis retrospective cohort study included patients > 2 years of age who had at least 2 episodes of CDI within the last year prior to broad-spectrum antibiotic exposure. The ppx cohort included patients who received oral vancomycin for > 50% of the duration of broad-spectrum antibiotic therapy, and the no ppx cohort included patients who received no oral vancomycin while on broad-spectrum antibiotics. Cohorts were compared via a univariate analysis. A Kaplan–Meier analysis was used to evaluate the time-to-event for development of CDI.ResultsOf 108 patients who met inclusion criteria, 88 patients were included in the no ppx cohort and 20 patients in the ppx cohort. The primary outcome of CDI incidence was numerically lower in the ppx cohort [13 (14.8%) vs. 2 (10%), p = 0.733]. Secondary outcomes within 12 weeks of broad-spectrum antibiotic initiation were similar between cohorts. The mean time from broad-spectrum antibiotic initiation to CDI recurrence was longer among the ppx cohort, suggesting a delay in time to CDI recurrence (29 + 25.9 vs. 57.5 + 26.1 days, p = 0.171). This delay led to a lower incidence of hospital acquired (HA) CDI in the ppx cohort [4 (30.8%) vs. 0 (0%), P > 0.99]. The Kaplan–Meier analysis (Figure 1) demonstrated no significant difference in time-to-event of CDI, p = 0.70.ConclusionThe use of oral vancomycin for secondary ppx of CDI was not shown to have a statistically significant difference in CDI recurrence compared with no ppx in this study. However, this may be due to the low sample size in the ppx cohort and low CDI event rates. The trend toward a delay in CDI recurrence and reduction in HA-CDI with the use of oral vancomycin is hypothesis generating. Further controlled studies are warranted to confirm the role of oral vancomycin for secondary ppx of CDI. Disclosures All authors: No reported disclosures.

Innovative intelligent insole system reduces diabetic foot ulcer recurrence at plantar sites: a prospective, randomised, proof-of-concept study

Prevention of diabetic foot ulcer recurrence in high risk patients, using current standard of care methods, remains a challenge. We hypothesised that an innovative intelligent insole system would be effective in reducing diabetic foot ulcer recurrence in such patients. In this prospective, randomised, proof-of-concept study, patients with diabetes, and with peripheral neuropathy and a recent history of plantar foot ulceration were recruited from two multidisciplinary outpatient diabetic foot clinics in the UK, and were randomly assigned to either intervention or control. All patients received an insole system, which measured plantar pressure continuously during daily life. The intervention group received audiovisual alerts via a smartwatch linked to the insole system and offloading instructions when aberrant pressures were detected; the control group did not receive any alerts. The primary outcome was plantar foot ulcer occurrence within 18 months. This trial is registered with ISRCTN, ISRCTN05585501, and is closed to accrual and complete. Between March 18, 2014, and Dec 20, 2016, 90 patients were recruited and consented to the study, and 58 completed the study. At follow-up, ten ulcers from 8638 person-days were recorded in the control group and four ulcers from 11 835 person-days in the intervention group: a 71% reduction in ulcer incidence in the intervention group compared with the control group (incidence rate ratio 0·29, 95% CI, 0·09-0·93; p=0·037). The number of patients who ulcerated was similar between groups (six of 26 [control group] vs four of 32 [intervention group]; p=0·29); however, individual plantar sites ulcerated more often in the control group (ten of 416) than in the intervention group (four of 512; p=0·047). In an exploratory analysis of good compliers (n=40), ulcer incidence was reduced by 86% in the intervention group versus control group (incidence rate ratio 0·14, 95% CI 0·03-0·63; p=0·011). In the exploratory analysis, plantar callus severity (change from baseline to 6 months) was greater in re-ulcerating patients (6·5, IQR 4·0-8·3) than non-re-ulcerating patients (2·0, 0·0-4·8; p=0·040). To our knowledge, this study is the first to show that continuous plantar pressure monitoring and dynamic offloading guidance, provided by an innovative intelligent insole system, can lead to a reduction in diabetic foot ulcer site recurrence. Diabetes UK and Orpyx Medical Technologies.

The Benefit of Reactivating p53 under MAPK Inhibition on the Efficacy of Radiotherapy in Melanoma.

Radiotherapy (RT) in patients with melanoma historically showed suboptimal results, because the disease is often radioresistant due to various mechanisms such as scavenging free radicals by thiols, pigmentary machinery, or enhanced DNA repair. However, radiotherapy has been utilized as adjuvant therapy after the complete excision of primary melanoma and lymph nodes to reduce the rate of nodal recurrences in high-risk patients. The resistance of melanoma cells to radiotherapy may also be in relation with the constitutive activation of the MAPK pathway and/or with the inactivation of p53 observed in about 90% of melanomas. In this study, we aimed to assess the potential benefit of adding RT to BRAF-mutated melanoma cells under a combined p53 reactivation and MAPK inhibition in vitro and in a preclinical animal model. We found that the combination of BRAF inhibition (vemurafenib, which completely shuts down the MAPK pathway), together with p53 reactivation (PRIMA-1Met) significantly enhanced the radiosensitivity of BRAF-mutant melanoma cells. This was accompanied by an increase in both p53 expression and activity. Of note, we found that radiation alone markedly promoted both ERK and AKT phosphorylation, thus contributing to radioresistance. The combination of vemurafenib and PRIMA-1Met caused the inactivation of both MAPK kinase and PI3K/AKT pathways. Furthermore, when combined with radiotherapy, it was able to significantly enhance melanoma cell radiosensitivity. Interestingly, in nude mice bearing melanoma xenografts, the latter triple combination had not only a synergistic effect on tumor growth inhibition, but also a potent control on tumor regrowth in all animals after finishing the triple combination therapy. RT alone had only a weak effect. In conclusion, we provide a basis for a strategy that may overcome the radioresistance of BRAF-mutated melanoma cells to radiotherapy. Whether this will translate into a rational to use radiotherapy in the curative setting in BRAF-mutated melanoma patients deserves consideration.