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Background Little is known about the influence of hepatic artery infusion pump (HAIP) therapy in the setting of chemotherapy resistant hepatic disease in the era of modern systemic therapies. Methods Patients who underwent HAIP therapy for chemotherapy resistant and unresectable colorectal liver metastases (CRLM) were reviewed retrospectively. Results A total of 25 patients met inclusion criteria. 52% had isolated CRLM and 92% had five or more metastatic lesions. Partial response was noted in 40% of patients. Median hepatic progression-free survival (PFS) was 7 months in those with extrahepatic disease versus 6 months in those with isolated CRLM at the time of HAIP placement (p = 0.75). Median overall survival was 8 months in patients with extrahepatic disease and 14 months in patients with isolated CRLM (p = 0.06). Conclusions Our findings are comparable to published data and augment the literature which supports HAIP use in chemotherapy-resistant, liver-predominant metastatic colorectal cancer patients.

Alkaloids isolated from members of the Amaryllidaceae plant family are promising anticancer agents. The purpose of the current study was to determine if the isocarbostyrils narciclasine, pancratistatin, lycorane, lycorine, crinane, and haemanthamine inhibit phenomena related to cancer progression in vitro. To achieve this, we examined the proliferation, adhesion, and invasion of cultured human colon cancer cells via MTT assay and Matrigel-coated Boyden chambers. In addition, Luminex assays were used to quantify the secretion of matrix metalloproteinases (MMP) and cytokines associated with poor clinical outcomes. We found that all alkaloids decreased cell proliferation regardless of TP53 status, with narciclasine exhibiting the greatest potency. The effects on cell proliferation also appear to be specific to cancer cells. Narciclasine, lycorine, and haemanthamine decrease both adhesion and invasion but with various potencies depending on the cell line. In addition, narciclasine, lycorine, and haemanthamine decreased the secretion of MMP-1, -2, and -7, as well as the secretion of the cytokines pentraxin 3 and vascular endothelial growth factor. In conclusion, the present study shows that Amaryllidaceae alkaloids decrease phenomena and cytokines associated with colorectal cancer progression, supporting future investigations regarding their potential as multifaceted drug candidates.

Stress in the context of the COVID-19 pandemic may have a significant impact on health, including sleep health. Older adults may be particularly vulnerable. This study examined associations between perceived stress and sleep health, mental health, physical health, and overall perceived health outcomes among older adults. We also examined whether specific coping strategies moderate these associations. Older adults (n = 115; M(age) = 68.62) reported perceived stress, coping strategies, global sleep quality, depressive symptoms, and perceived mental, physical, and overall health before and during the COVID-19 pandemic. Stress-health relationships were modelled with hierarchical linear regression. Higher perceived stress was associated with greater depressive symptoms and poorer mental health concurrently and longitudinally. Coping strategies moderated the association of perceived stress with physical health and overall perceived health. For example, higher perceived stress was associated with poorer overall perceived health among those with lower problem-focussed coping, but not among those with higher problem-focussed coping. Older adults may benefit from prevention and intervention strategies targeting stress management. Furthermore, identifying people with low problem-focussed coping might be a useful strategy to prevent worsening health in future public health crises.

Reproducible identification of white matter pathways across subjects is essential for the study of structural connectivity of the human brain. One of the key challenges is anatomical differences between subjects and human rater subjectivity in labeling. Labeling white matter regions of interest presents many challenges due to the need to integrate both local and global information. Clearly communicating the manual processes to capture this information is cumbersome, yet essential to lay a solid foundation for comprehensive atlases. Segmentation protocols must be designed so the interpretation of the requested tasks as well as locating structural landmarks is anatomically accurate, intuitive and reproducible. In this work, we quantified the reproducibility of a first iteration of an open/public multi-bundle segmentation protocol. This allowed us to establish a baseline for its reproducibility as well as to identify the limitations for future iterations. The protocol was tested/evaluated on both typical 3 T research acquisition Baltimore Longitudinal Study of Aging (BLSA) and high-acquisition quality Human Connectome Project (HCP) datasets. The results show that a rudimentary protocol can produce acceptable intra-rater and inter-rater reproducibility. However, this work highlights the difficulty in generalizing reproducible results and the importance of reaching consensus on anatomical description of white matter pathways. The protocol has been made available in open source to improve generalizability and reliability in collaboration. The goal is to improve upon the first iteration and initiate a discussion on the anatomical validity (or lack thereof) of some bundle definitions and the importance of reproducibility of tractography segmentation.

The Ophthalmology Student Interest Group at Indiana University School of Medicine provides a free student-run eye screening clinic for an underserved community in Indianapolis. Patients with abnormal findings are referred to the ophthalmology service of the local county hospital for further evaluation. This retrospective chart review studied 180 patients referred from our free eye clinic to follow up at the ophthalmology service of a local county hospital from October 2013 to February 2020. This study investigated factors impacting follow-up of patients by analyzing demographics, medical history, insurance coverage, and final diagnoses at follow-up. Thirty-five (19.4%) of 180 patients successfully followed up at the local county hospital with an average time to follow-up of 14.4 (± 15.9) months. Mean patient age was 51 (± 13.6) with nearly equal numbers of males and females. The most common diagnoses at follow-up included refractive error (51.4%), cataract (45.7%), and glaucoma (28.6%). Patients with diabetes diagnoses or Healthy Indiana Plan insurance coverage had increased probability of follow-up. This study reveals gaps in timely follow-up to the local county hospital, demonstrating the current limitations of our free clinic in connecting patients to more definitive care and the need for an improved referral process.

Background The Indiana University Student Outreach Clinic (IUSOC) Eye Clinic is a monthly student-run eye clinic that provides free visual screening to the Near East Side community of Indianapolis, IN, USA. Screening includes assessments of visual acuity, intraocular pressure, peripheral visual fields, refraction, and non-mydriatic fundus photography. Methods This is a retrospective chart review of 875 patients seen at the IUSOC Eye Clinic from October 2013 to February 2020. Data on demographics, insurance coverage, ocular history, physical examination, suspected diagnosis, referral status, and glasses provided were collected and analyzed. Results 875 patients were seen at the IUSOC Eye Clinic from October 2013 to February 2020. 39.2% of the patients seen at the clinic reported being uninsured. 61.4% of patients were found to have visual acuity of 20/40 or worse, while 51.3% of patients were found to have a near visual acuity of 20/40 or worse. 20.3% of patients were referred to the local county hospital for further evaluation by an ophthalmologist, 14.4% of patients received free glasses prescriptions, and 27.9% of patients received free reading glasses. Common reasons for referral for further ophthalmology evaluation included glaucoma, decreased visual acuity, and diabetic retinopathy. An estimated value of services provided over the seven years of the clinic was 1271 relative value units. Conclusion The IUSOC Eye Clinic fills an important role in advancing ocular health and preventing irreversible blindness in an underserved Indianapolis community. Additionally, the clinic demonstrates an educational model for involving medical student volunteers.

ObjectiveOvarian metastases occur in 3%–5% of patients with colorectal cancer. The role of oophorectomy in that setting continues to be debated. We aimed to assess the survival of women treated with metastasectomy for ovarian metastasis.MethodsRetrospective cohort study of patients in the California Cancer Registry (2000–2012) with stage IV colorectal cancer and ovarian metastases. Pathology other than adenocarcinoma was excluded. Adjusted Cox-proportional hazard analysis was applied to assess the risk of death.ResultsA total of 756 patients with synchronous ovarian metastases and 516 patients with metachronous ovarian metastases form the basis of this analysis. Median follow-up for the synchronous cohort was 21 months (IQR: 8–36). Median overall survival was 23 months (IQR: 10–42). Estimated 5-year survival reached 17% and 10-year survival was 8%. There was a significant difference in unadjusted survival between patients with solitary ovarian metastasis (median overall survival: 51 months) compared with those who had both ovarian and extraovarian metastases (20 months) (log-rank test, PConclusionsPatients with colorectal cancer ovarian metastasis have favorable long-term survival. Survival rates are higher if the tumor is isolated to the ovary or if metachronous to the primary cancer.

Although there is a commonly held belief within the baseball community that delivery from the stretch confers more stress at the elbow and shoulder joints than delivery from the windup, there remains little evidence in the literature investigating this hypothesis. This study aimed to help address this gap in the literature by studying both intra-pitcher kinematic sequence variability, and intra-pitcher joint torque variability when throwing from the windup vs. the stretch. We hypothesized that 1) each pitchers’ kinematic sequence would remain similar whether throwing from the windup or stretch, and 2) Kinematic sequence would influence peak arm torque more than delivery method. This cross-sectional 3D biomechanical study included 88 pitches thrown by ten (6 collegiate, 4 high school) pitchers with a mean age of 17.60 ± 2.63 years. Pitch velocity, throwing shoulder/elbow torques and the kinematic sequence of each pitch utilizing segmental peak angular velocities were captured. No statistically significant differences in ball velocity (p = 0.17), peak shoulder external rotation torque (p = 0.80), shoulder extension torque (p = 0.97), or elbow valgus torque (p = 0.83) were found between delivery approaches. Three primary kinematic sequences were identified. Shoulder external rotation torque [F(53,2) = 10.992, ɳ2 = .293, p < 0.00], shoulder extension torque [F(53,2) = 15.517, ɳ2 = .369, p < 0.00] and elbow valgus torque [F(53,2) = 9.994, ɳ2 = .274, p < 0.00] did vary significantly across these three kinematic sequence patterns. Our data suggest that the kinematic sequence influences shoulder and elbow torque more than the delivery approach. Instructing ideal kinematic sequence may be more influential for injury avoidance than delivery method.

Aim: The addition of etidronic acid (HEDP) to sodium hypochlorite (NaOCl) could increase the antibiofilm potency of the irrigant, whilst maintaining the benefits of continuous chelation. Studies conducted so far have shown that mixing HEDP with NaOCl solutions of relatively low concentration does not compromise the antibiofilm efficacy of the irrigant. However, the working lifespan of NaOCl may decrease resulting in a reduction of its antibiofilm efficacy over time (efficiency). In this regard, continuous irrigant replenishment needs to be examined. This study investigated the response of a dual-species biofilm when challenged with 2% and 5% NaOCl mixed with HEDP for a prolonged timespan and under steady laminar flow.Methodology: Dual-species biofilms comprised of Streptococcus oralis J22 and Actinomyces naeslundii T14V-J1 were grown on human dentine discs in a constant depth film fermenter (CDFF) for 96 h. Biofilms were treated with 2% and 5% NaOCl, alone or mixed with HEDP. Irrigants were applied under steady laminar flow for 8 min. Biofilm response was evaluated by means of optical coherence tomography (OCT). Biofilm removal, biofilm disruption, rate of biofilm loss and disruption as well as bubble formation were assessed. One-way anova, Wilcoxon's signed-rank test and Kruskal–Wallis H test were performed for statistical analysis of the data. The level of significance was set at a ≤.05.Results: Increasing NaOCl concentration resulted in increased biofilm removal and disruption, higher rate of biofilm loss and disruption and increased bubble formation. Mixing HEDP with NaOCl caused a delay in the antibiofilm action of the latter, without compromising its antibiofilm efficacy.Conclusions: NaOCl concentration dictates the biofilm response irrespective of the presence of HEDP. The addition of HEDP resulted in a delay in the antibiofilm action of NaOCl. This delay affects the efficiency, but not the efficacy of the irrigant over time.

PURPOSE: Disease recurrence after radical cystectomy generally occurs within 2 years and has a poor prognosis. Less well defined are the outcomes in patients who experience a late recurrence (>3 years after radical cystectomy). We report our institutional experience with late recurrences and describe the relationships between time to recurrence, management strategies, and survival. MATERIALS AND METHODS: The study cohort comprised 2,315 patients who underwent radical cystectomy for urothelial carcinoma at our center between 2000 and 2014, of whom 617 had a recurrence. Median follow-up for survivors was 2.6 years post-recurrence (IQR 0.95–4.5). For the study, we considered disease recurrence as recurrences outside the urinary tract. We compared baseline characteristics and post-recurrence management between those with recurrence ≤3 and >3 years after radical cystectomy. RESULTS: 58 patients with late recurrence had significantly lower consensus T stage and lower frequency of nodal involvement. The average 1-year bladder cancer death rate from the time of recurrence declined from 66% to 50% to 33% for patients with recurrence times of 6 months, 2 years, and 5 years after radical cystectomy, respectively. For patients who survived at least 1 year after recurrence, the estimated survival at 5 years after recurrence was 45% for late recurring patients and 21% for patients who had an early recurrence. Local consolidative therapy (metastasectomy or radiation) was more common in patients with late recurrence (19% vs. 3.6%, p < 0.0001), and cancer-specific survival in early-recurring patients was significantly worse than in late-recurring patients in the subset receiving local consolidation (p = 0.02). CONCLUSIONS: The prolonged lifespan of patients experiencing a late recurrence after radical cystectomy can be leveraged to individualize management. There is strong rationale for investigating the role of metastasectomy in the management of late recurrences.

Objective: The COVID-19 pandemic requires to conscientiously weigh “timely surgical intervention” for colorectal cancer against efforts to conserve hospital resources and protect patients and health care providers. Summary Background Data: Professional societies provided ad-hoc guidance at the outset of the COVID-19 pandemic on deferral of surgical and perioperative interventions, but these lack specific parameters to determine the optimal timing of surgery. Methods: Using the GRADE system, published evidence was analyzed to generate weighted statements for stage, site, acuity of presentation, and hospital setting to specify when surgery should be pursued, the time and duration of oncologically acceptable delays, and when to utilize nonsurgical modalities to bridge the waiting period. Results: Colorectal cancer surgeries—prioritized as emergency, urgent with imminent emergency or oncologically urgent, or elective—were matched against the phases of the pandemic. Surgery in COVID-19-positive patients must be avoided. Emergent and imminent emergent cases should mostly proceed unless resources are exhausted. Standard practices allow for postponement of elective cases and deferral to nonsurgical modalities of stage II/III rectal and metastatic colorectal cancer. Oncologically urgent cases may be delayed for 6(–12) weeks without jeopardizing oncological outcomes. Outside established principles, administration of nonsurgical modalities is not justified and increases the vulnerability of patients. Conclusions: The COVID-19 pandemic has stressed already limited health care resources and forced rationing, triage, and prioritization of care in general, specifically of surgical interventions. Established guidelines allow for modifications of optimal timing and type of surgery for colorectal cancer during an unrelated pandemic.

BACKGROUND. Growing evidence has documented the adverse impact of the global COVID-19 pandemic on sleep quality among older adults. Given the negative consequences of poor sleep, it is critical to identify factors that provide older adults with resilience against worsening sleep quality. Social integration may represent one such resilience factor. PURPOSE. This study evaluated the association of social integration and sleep quality during the COVID-19 pandemic. METHODS. 113 retired older adults completed assessments of their social integration after the onset of the COVID-19 pandemic, and of their sleep quality before and after the onset of the COVID-19 pandemic. RESULTS. Higher levels of social integration were associated with better sleep quality during the COVID-19 pandemic, even when statistically controlling for pre-pandemic sleep quality. Sex-stratified analyses showed that this association was driven by women in our sample. CONCLUSIONS. Social integration may confer resilience against poor sleep quality, especially in older adult women. Additional research is warranted to assess candidate mechanisms and moderators of the link between social integration and sleep quality.

PURPOSE: Artificial intelligence diagnosis and triage of large vessel occlusion may quicken clinical response for a subset of time-sensitive acute ischemic stroke patients, improving outcomes. Differences in architectural elements within data-driven convolutional neural network (CNN) models impact performance. Foreknowledge of effective model architectural elements for domain-specific problems can narrow the search for candidate models and inform strategic model design and adaptation to optimize performance on available data. Here, we study CNN architectures with a range of learnable parameters and which span inclusion of architectural elements, such as parallel processing branches and residual connections with varying methods of recombining residual information. METHODS: We compare five CNNs: ResNet-50, DenseNet-121, EfficientNet-B0, PhiNet, and an Inception module-based network, on a computed tomography angiography large vessel occlusion detection task. The models were trained and preliminarily evaluated with 10-fold cross-validation on preprocessed scans (n=240). An ablation study was performed on PhiNet due to superior cross-validated test performance across accuracy, precision, recall, specificity, and F1 score. The final evaluation of all models was performed on a withheld external validation set (n=60) and these predictions were subsequently calibrated with sigmoid curves. RESULTS: Uncalibrated results on the withheld external validation set show that DenseNet-121 had the best average performance on accuracy, precision, recall, specificity, and F1 score. After calibration DenseNet-121 maintained superior performance on all metrics except recall. CONCLUSIONS: The number of learnable parameters in our five models and best-ablated PhiNet directly related to cross-validated test performance—the smaller the model the better. However, this pattern did not hold when looking at generalization on the withheld external validation set. DenseNet-121 generalized the best; we posit this was due to its heavy use of residual connections utilizing concatenation, which causes feature maps from earlier layers to be used deeper in the network, while aiding in gradient flow and regularization.

Biomarkers of ocular blood flow originating from a wide variety of imaging modalities have been associated with glaucoma onset and progression for many decades. Advancements in imaging platforms including optical coherence tomography angiography (OCTA) have provided the ability to quantify vascular changes in glaucoma patients, alongside traditional measures such as retinal nerve fiber layer thickness (RNFL) and optic nerve head (ONH) structure. Current literature on vascular biomarkers, as measured by OCTA, indicates significant relationships between glaucoma and blood flow and capillary density in the retina and ONH. The data currently available, however, is highly diverse and lacks robust longitudinal data on OCTA vascular outcomes and glaucoma progression. Herein we discuss and summarize the relevant current literature on OCTA vascular biomarkers and glaucoma reviewed from December 14, 2020 through March 1, 2021. Associations between OCTA vascular biomarkers and clinical structural and functional glaucoma outcomes as well as differences between glaucoma patients and healthy controls are reviewed and summarized. The available data identifies significantly decreased flow density, flow index, and vessel density in the ONH, peripapillary vascular layer, and macula of glaucoma patients compared to controls. Whole image vessel density is also significantly decreased in glaucoma patients compared to controls and this outcome has been found to correspond to severity of visual field loss. OCTA vascular biomarkers alongside clinical structural outcomes may aid in assessing overall risk for glaucoma in patients.

Objective To assess the comparative risk of recurrence and ostomy after elective resection or medical therapy for uncomplicated diverticulitis, incorporating outpatient episodes of recurrence. Background While surgeons historically recommended colon resection for uncomplicated diverticulitis to reduce the risk of recurrence or colostomy, no prior studies have quantified this risk when considering outpatient episodes of disease. It remains to be determined whether surgery actually decreases those risks. Methods Retrospective cohort study employing an adjusted time-to-event analysis to assess the relationship of medical or surgical treatment with diverticulitis recurrence and/or receipt of an ostomy. Subjects were adults with ≥1 year continuous enrollment treated for ≥2 episodes of uncomplicated diverticulitis from a nationwide commercial claims dataset (2008-2014). Results Of 12,073 patients (mean age 56 ± 14 yr, 59% women), 19% underwent elective surgery and 81% were treated by medical therapy on their second treatment encounter for uncomplicated diverticulitis. At 1 year, patients treated by elective surgery had lower rates of recurrence (6%) versus those treated by medical therapy (32%) [15% vs 61% at 5 years, adjusted hazard ratio 0.17 (95% confidence interval: 0.15-0.20)]. At 1 year, the rate of ostomy after both treatments was low [surgery (inclusive of stoma related to the elective colectomy), 4.0%; medical therapy, 1.6%]. Conclusions Elective resection for uncomplicated diverticulitis decreases the risk of recurrence, still 6% to 15% will recur within 5 years of surgery. The risk of ostomy is not lower after elective resection, and considering colostomies related to resection, ostomy prevention should not be considered an appropriate indication for elective surgery.

De novo heterozygous missense mutations in TRPM3 have been shown to cause developmental and epileptic encephalopathies (DEE). It is a very rare condition, as only 9 patients have been described to date. We report here a novel patient carrying the recurrent p.Val837Met variant and presenting new clinical features, such as trigonocephaly, expanding the phenotypical spectrum of the disease.

While robotic surgery has grown in popularity and scope over the past decade, there is a persistent need for simulation-based training as surgeons adapt from the working at the bedside to the immersive and multisensory tasks at the console. From dry laboratory to virtual reality (VR) environments, simulation can be used to train surgeons in basic tasks, complex operative steps, and coordination of whole operations with members of the entire operating room (OR) staff. By integrating simulation into mentored training programs, surgeons can reduce the number of cases required to master a complex operation. Future VR based simulation will become essential to the adaptation of the surgical workforce to new technologies and adoption of emerging robotic platforms. Ultimately, robotic simulation will set standards for credentialing of new surgeons.

Attributable to the high likelihood of developing distant metastatic disease, resection of poorly differentiated gastroenteropancreatic neuroendocrine neoplasms is generally contraindicated. Some patients with no distant metastatic disease will nonetheless undergo surgical resection and their outcomes are not known. We aimed to determine whether surgery confers survival advantage over systemic therapy alone for patients with non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms.We performed a retrospective cohort study (2000-2012) of adults in the California Cancer Registry who had poorly differentiated gastroenteropancreatic neuroendocrine neoplasms (World Health Organization Grade 3) and no clinical evidence of distant metastasis (M0). Patients who underwent surgery were compared with those managed non-operatively. The adjusted Cox proportional hazards model was used to assess the risk of death.Among 2,245 patients (45% female, 21% pancreatic, 79% gastrointestinal), 1,549 (69%) were treated with surgery, and 696 (31%) received either systemic therapy or palliative measures alone. Median survival was 31 months after surgery versus 9 months after non-operative therapy (log-rank test, P.001). Rates of 5-year overall survival were 39% after surgery versus 10% in the non-operative group. Adjusting for age, sex, comorbidities, receipt of chemotherapy, and tumor size and location, patients treated with surgery had a 58% lower likelihood of death compared with non-operative therapy (hazard ratio: 0.42, 95% confidence interval: 0.36-0.50, P.001). Restricting our results to those patients who were found to have no distant metastasis intraoperatively (ie, pathologically M0), 5-year survival after surgery reached 44%.While poorly differentiated gastroenteropancreatic neuroendocrine neoplasms carries a poor prognosis, for patients with no evidence of metastatic disease, resection appears to confer significant improvement in long-term survival. Although caution and an individualized approach in treating poorly differentiated gastroenteropancreatic neuroendocrine neoplasms is advised, future guidelines might reflect this survival advantage.

A subset of metachronous colon cancer recurrence manifests as peritoneal metastases (PM). Risk factors for metachronous PM recurrence are not well-defined in patients with stage II or III colon cancers after curative resection and standard adjuvant treatments.Population data from the California Cancer Registry for patients with Stage II or III colon cancer were collected between 2004 and 2012. Multivariate analysis was used to identify factors associated with metachronous PM.Of the 2077 patients with stage II or III colon cancer, female patients (odds ratio [OR] = 1.84, p = 0.02), T4 primary tumor (OR = 2.36, p = 0.02), mucinous (OR = 3.97, p 0.01) or signet-ring histology (OR = 6.01, p = 0.01), and right-sided cancer (OR = 2.2, p 0.01) were found with increased risk of metachronous isolated PM recurrence after curative resection. Median survival after diagnosis for patients without PM recurrence was 22 months, compared with 12 months for PM recurrence (p 0.001).PM recurrence groups have a worse overall survival than patients with recurrent disease in other sites. A better understanding of the tumor biology and molecular characteristics of colon cancers likely to recur as PM is needed to explain behavior and identify potential targeted therapy.

PURPOSE: To evaluate trends in oncologic characteristics and outcomes, as well as perioperative management, among patients undergoing radical cystectomy at Memorial Sloan Kettering from 1995 to 2015. MATERIALS AND METHODS: We retrospectively reviewed our institutional database to analyze changes in disease recurrence probability, cancer-specific and all-cause mortality, incidence of muscle-invasive bladder cancer, use of perioperative chemotherapy, rate of positive soft-tissue surgical margins, and lymph node yield. RESULTS: In 2,740 patients with non-metastatic urothelial carcinoma undergoing radical cystectomy from 1995 to 2015, the 5-year probability of disease recurrence decreased from a peak of 42% in 1997 to 34% in 2013 (p=0.045), while 5-year probability of cancer-specific mortality likewise declined from 36% in 1997 to 24% in 2013 (p=0.009). Incidence of non-muscle-invasive disease before radical cystectomy did not change, comprising 30%–35% of patients across the study period. Use of neoadjuvant chemotherapy rose significantly: 57% of patients with muscle-invasive bladder cancer from 2010 to 2015 received it. We observed a corresponding rise in complete pathologic response (pT0) at radical cystectomy, as well as decreasing positive soft-tissue surgical margins (10% to 2.5%) and rising lymph node yield (7 to 24) from 1995 to 2015. CONCLUSIONS: Over a 21-year period, outcomes after radical cystectomy at our institution improved significantly, as probability of recurrence and cancer-specific mortality decreased. Increasing utilization of neoadjuvant chemotherapy, rising pT0 rates, decreased positive soft-tissue surgical margins, and increasing lymph node yields likely contributed, suggesting that optimized surgical and perioperative care led to improved cancer outcomes in patients undergoing radical cystectomy.

PURPOSE: To determine the diagnostic performance of (18)F-FDG PET/CT for detecting nodal metastases in patients with muscle-invasive urothelial bladder cancer prior to radical cystectomy. MATERIALS AND METHODS: Preoperative (18)F-FDG PET/CT scans (n = 208) were retrospectively reviewed. Scans were routinely performed in 185 patients with muscle-invasive urothelial bladder cancer between August 2012 and February 2017, all of whom underwent radical cystectomy and pelvic lymph node dissection. Analyses were stratified by clinical node involvement and chemotherapy status. The diagnostic performance of (18)F-FDG PET/CT was assessed according to sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: Lymph node metastases at time of PLND were present in 21.8% of those without suspicious nodes on computed tomography (clinically node negative) and 52.6% of those with suspicious nodes on CT (clinically node positive). Median metastatic focus size was 5 mm. In clinically node negative patients, (18)F-FDG PET/CT rarely detected nodal metastases (sensitivity 7–23%). In clinically node positive patients, a negative (18)F-FDG PET/CT was useful in ruling out lymph node metastases (sensitivity 92–100%). This study was limited by its mixed population and focus on pelvic nodal metastases only. CONCLUSIONS: (18)F-FDG PET/CT appears to be most useful for better characterization of enlarged nodes identified by CT. Routine preoperative (18)F-FDG PET/CT has limited utility in clinically node-negative patients.

AimsTo examine the relationship between baseline structural characteristics of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) and functional disease progression in patients with open-angle glaucoma (OAG) over 5 years.Methods112 OAG patients were prospectively examined at baseline and every 6 months over a period of five years. Structural glaucomatous changes were examined with optical coherence tomography (OCT) and Heidelberg retinal tomography-III (HRT-III), and functional disease progression with automated perimetry (Humphrey visual fields). Cox proportional hazard models were used to assess the relationship between baseline structural measurements and functional disease progression.ResultsFrom baseline over a 5-year period, statistically significant increases were found in OCT disc (D) area (pConclusionBaseline ONH and RNFL structural characteristics were associated with a significantly shorter time to functional glaucomatous progression and visual field loss through the five-year period in OAG patients.

The proximity of cerebrospinal fluid (CSF) with the brain, its permanent renewal and better availability for research than tissue biopsies, as well as ganglioside (GG) shedding from brain to CSF, impelled lately the development of protocols for the characterization of these glycoconjugates and discovery of central nervous system biomarkers expressed in CSF. Currently, the investigation of CSF gangliosides is focused on concentration measurements of the predominant classes and much less on their profiling and structural analysis. Since we have demonstrated recently the high performance of ion mobility separation mass spectrometry (IMS MS) for compositional and structural determination of human brain GGs, in the present study we have implemented for the first time IMS MS for the exploration of human CSF gangliosidome, in order to generate the first robust mass spectral database of CSF gangliosides. IMS MS separation and screening revealed 113 distinct GG species in CSF, having similar compositions to the species detected in human brain. In comparison with the brain tissue, we have discovered in CSF several components containing fatty acids with odd number of carbon atoms and/or short glycan chains. By tandem MS (MS/MS) we have further analyzed the structure of GD3(d18:1/18:0) and GD2(d18:1/18:0), two glycoforms exhibiting short carbohydrate chains found in CSF, but discovered and characterized previously in brain as well. According to the present results, human CSF and brain show a similar ganglioside pattern, a finding that might be useful in clinical research focused on discovery of ganglioside species associated to neurodegenerative diseases and brain tumors.

Enhanced recovery after surgery (ERAS) protocols are now commonplace in many fields of surgery, but only limited data exists for their use in hepatobiliary surgery. We implemented standardized ERAS protocols for all open hepatectomies and replaced thoracic epidurals with a transversus abdominis plane (TAP) block. We performed a retrospective cohort study of all patients undergoing open hepatectomy during the 14 months before and 19 months after implementation of an ERAS protocol at our institution (January 2014–September 2016). Trained abstractors reviewed charts for patient demographics, perioperative details, and healthcare utilization. All nursing-reported visual analog scale pain scores were sampled to identify patients with uncontrolled pain (daily mean score > 5). Outcomes included length of stay (LOS), costs, and 30-day readmission. A total of 127 patients (mean age 54.6 ± 13.0 years, 44% female) underwent open liver resection (69 [54%] after ERAS implementation). ERAS protocols were associated with significantly lower rates of ICU admission (47 vs. 13%, p

Surgical repair or drainage is the standard treatment for benign esophageal perforation. The United States Food and Drug Administration has approved the use of esophageal stents for the management of malignant esophageal stricture or fistula, or both. We hypothesize that increasing enthusiasm and experience with esophageal stents has led to greater use of stents for the management of benign esophageal perforation.We performed a retrospective cohort study (2007 to 2014) of patients with benign esophageal perforation using MarketScan (Thomson Reuters, New York, NY), a commercial claims database. Patients had 6 months of follow-up. Regression was used for risk-adjustment.Benign esophageal perforation was treated in 659 patients (mean age, 49 years; 41% women), comprising surgical repair in 449 (69%), surgical drainage in 110 (17%), and stent in 100 (15%). Stent use increased from 7% in 2007 to 30% in 2014 (p0.001 for trend). Over the same period, surgical repair decreased from 71% to 53% (p = 0.001 for trend), but surgical drainage did not change (p = 0.24). After adjustment for other factors that could vary over time, stent use increased by 28% per year (incidence rate ratio, 1.28; 95% confidence interval, 1.17 to 1.39). Changes in risk-adjusted deaths, discharges home, readmissions, or costs over the same period were not significant (all p0.05 for trend).The use of stents for the management of benign esophageal perforation has increased by over fourfold in just 8 years, but short-term outcomes have not changed over time for this population of patients. A national registry for off-label use of esophageal stents may clarify the indications for and risks and benefits of stenting benign esophageal perforations.

Burst stimulation, as described by DeRidder, is a novel waveform made up of closely spaced, high-frequency electrical impulses delivered in packets, which are followed by a quiescent period or interburst interval. Electrically generated burst waveforms were initially designed to treat neural pathology in the auditory cortex and were later applied to the spinal cord through spinal cord stimulation (SCS) devices to treat chronic pain states. When Burst stimulation is applied to the spinal cord, the impulses travel to the thalamus and then diverge, targeting both the somatosensory cortex and the limbic system where they treat both the sensory, affective and attentional components of neuropathic pain. Areas covered: Literature examining clinical and basic research findings with the application of Burst stimulation to pathologically active central neural tissue was found using bibliographic databases including PubMed, Medline, Cochrane, Embase and Google Scholar. Expert commentary: Burst stimulation offers a salvage strategy for failed tonic spinal cord stimulation (tSCS), thus improving both quality of life and cost-effectiveness of SCS by reducing explant rates. The goal of this therapy is to use more than one waveform in the same device so that lost efficacy from tSCS can be salvaged.

Objectives Percutaneous radiofrequency ablation (RFA) of the gasserian ganglion through the foramen ovale and the glossopharyngeal nerve at the jugular foramen is a classical approach to treating trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GPN), respectively. However, it can be technically challenging with serious complications. We have thus developed a novel technique utilizing C-arm and computerized tomography (CT) guidance to block TN and GPN. Our goals were to describe a three-dimensional image-based technique to improve patient comfort and to decrease procedural time associated with needle guidance. Study design Consecutive procedures were reviewed. Setting Academic hospital. Methods Three patients with classical TN and GPN and 15 patients with atypical facial pain (AFP) were treated. Numeric rating scale (NRS) scores for pain at pretreatment and at one, three, and 12 months post-treatment were recorded. The primary clinical outcome (50% or more reduction in NRS) and secondary adverse clinical outcome (hematoma, facial numbness, etc.) were monitored. Results We had a 100% technical success with respect to appropriate needle positioning. All three classical TN/GPN patients had both immediate and sustained pain relief. Complications were minimal. The 15 AFP patients, however, showed more variable results, with only five (33%) having sustained pain relief, while in the other 10 (67%) patients, we observed suboptimal response. Conclusions We present a novel method and single-center experience with C-arm and CT-guided RFA of facial pain. Quick and accurate needle placement will help future advancements in the RFA algorithm so that more durable and consistent effects can be attained, reducing uncertainty with respect to needle placement as a confounder. The RFA procedure in our study had a satisfying effect for classical TN/GPN patients but was less successful for AFP patients, though it did mirror the results from previous studies. Limitations This study is limited by its small sample size and nonrandomized design.

Introduction Improving coordination during transitions of care from the hospital to Skilled Nursing Facilities (SNF)s is critical for improving healthcare quality. In 2014, we formed ( Improving Nursing Facility Outcomes using Real-Time Metrics , INFORM) to improve transitions of care by identifying structural and process factors that lead to poor clinical outcomes and hospital readmission. Methods Stakeholders from 10 SNFs and 4 hospitals collaborated to assess the current hospital and system-level challenges to safe transitions of care and identify targets for interventions. Results The INFORM collaborative identified areas for improvement including improving accuracy and timeliness of discharge information, facilitating congruent medication reconciliation, and developing care plans to support functional improvement. Discussion Hospital and SNF stakeholder engagement prioritized the challenges in patient transitions from inpatient to skilled nursing facility settings. Innovative solutions that address barriers to safe and effective transitions of care are critical to improving clinical outcomes, decreasing adverse events and avoiding readmission.

Background and aims The risk effect of anxiety on addictive behaviors, including Internet addiction (IA), has repeatedly been highlighted in the international literature. However, there is a lack of longitudinal studies examining this association in relation to proximal context effects, particularly in adolescence. Such findings would shed light on potential age- and proximal context-related variations in the anxiety–IA association that could better inform IA prevention and intervention initiatives. Methods In this study, 648 adolescents, embedded in 34 classrooms, were assessed at the age of 16 and again at the age of 18 to examine the effect of anxiety on IA behaviors in relation to the average level of classroom extraversion. IA was assessed with the Internet Addiction Test (Young, 1998), anxiety with the relevant subscale of the Symptom Checklist 90 – Revised (Derogatis & Savitz, 1999) and classroom extraversion with the synonymous subscale of the Five Factor Questionnaire (Asendorpf & van Aken, 2003). A three-level hierarchical linear model was calculated. Results The present findings demonstrated that: (a) higher levels of anxiety were significantly associated with higher IA behaviors, (b) the strength of this association did not vary over time (between 16 and 18 years old), and (c) however, it tended to weaken within classrooms higher in extraversion. Discussion This study indicated that the contribution of individual IA risk factors might differently unfold within different contexts.

Randomized controlled trials demonstrate the efficacy of arginine-enriched nutritional supplements (immunonutrition) in reducing complications after surgery. The effectiveness of preoperative immunonutrition has not been evaluated in a community setting.This study aims to determine whether immunonutrition before elective colorectal surgery improves outcomes in the community at large.This is a prospective cohort study with a propensity score-matched comparative effectiveness evaluation.This study was conducted in Washington State hospitals in the Surgical Care Outcomes Assessment Program from 2012 to 2015.Adults undergoing elective colorectal surgery were selected.Surgeons used a preoperative checklist that recommended that patients take oral immunonutrition (237 mL, 3 times daily) for 5 days before elective colorectal resection.Serious adverse events (infection, anastomotic leak, reoperation, and death) and prolonged length of stay were the primary outcomes measured.Three thousand three hundred seventy-five patients (mean age 59.9 ± 15.2 years, 56% female) underwent elective colorectal surgery. Patients receiving immunonutrition more commonly were in a higher ASA class (III-V, 44% vs 38%; p = 0.01) or required an ostomy (18% vs 14%; p = 0.02). The rate of serious adverse events was 6.8% vs 8.3% (p = 0.25) and the rate of prolonged length of stay was 13.8% vs 17.3% (p = 0.04) in those who did and did not receive immunonutrition. After propensity score matching, covariates were similar among 960 patients. Although differences in serious adverse events were nonsignificant (relative risk, 0.76; 95% CI, 0.49-1.16), prolonged length of stay (relative risk, 0.77; 95% CI, 0.58-1.01 p = 0.05) was lower in those receiving immunonutrition.Patient compliance with the intervention was not measured. Residual confounding, including surgeon-level heterogeneity, may influence estimates of the effect of immunonutrition.Reductions in prolonged length of stay, likely related to fewer complications, support the use of immunonutrition in quality improvement initiatives related to elective colorectal surgery. This population-based study supports previous trials of immunonutrition, but shows a lower magnitude of benefit, perhaps related to compliance or a lower rate of adverse events, highlighting the value of community-based assessments of comparative effectiveness.

To evaluate diurnal variations in optic nerve head (ONH) vessel density assessed by optical coherence tomography angiography (OCT-A) in healthy subjects, ocular hypertension (OHT), and open-angle glaucoma (OAG) patients.Forty subjects (OAG, 21; OHT, 6; healthy, 13) were assessed for vessel density percentage (VD%) and flow index in the ONH (NH VD%, NH index), and in the radial peripapillary capillary layer (RPC VD%, RPC index) at 9:00, 11:00, 14:00, 16:00, and 18:00 on a single day. Repeated measures ANOVAs were used to test for changes in the parameters measured at multiple time points.All OCT-A parameters analyzed at the different time points were statistically lower in the OAG patients compared to both the OHT and healthy groups (p 0.05). In the OAG group, the NH index, RPC index, NH VD%, and RPC VD% were statistically lower at 18:00 compared to 14:00, and the RPC VD% was statistically lower at 9:00 than 14:00. In the OHT group, the RPC index was statistically lower at 9:00 than 11:00. In the healthy group, the NH VD% and RPC VD% were statistically lower at 16:00 than 18:00, and the RPC index was statistically lower at 9:00 than 11:00. No other statistically significant difference was found in none of the three groups comparing any other time point (p 0.05).In healthy subjects, OHT and OAG patients, the variations in the OCT-A derived parameters were relatively small. These results suggest that in the clinical practice the OCT-A assessment can be performed independently of the time of the day, contrasting IOP evaluation.

HIMF (hypoxia-induced mitogenic factor; also known as FIZZ1 [found in inflammatory zone-1] or RELM [resistin-like molecule-α]) is an etiological factor of pulmonary hypertension (PH) in rodents, but its underlying mechanism is unclear. We investigated the immunomodulatory properties of HIMF signaling in PH pathogenesis. Approach and Results: Gene-modified mice that lacked HIMF (KO [knockout]) or overexpressed HIMF human homolog resistin (hResistin) were used for in vivo experiments. The pro-PH role of HIMF was verified in HIMF-KO mice exposed to chronic hypoxia or sugen/hypoxia. Mechanistically, HIMF/hResistin activation triggered the HMGB1 (high mobility group box 1) pathway and RAGE (receptor for advanced glycation end products) in pulmonary endothelial cells (ECs) of hypoxic mouse lungs in vivo and in human pulmonary microvascular ECs in vitro. Treatment with conditioned medium from hResistin-stimulated human pulmonary microvascular ECs induced an autophagic response, BMPR2 (bone morphogenetic protein receptor 2) defects, and subsequent apoptosis-resistant proliferation in human pulmonary artery (vascular) smooth muscle cells in an HMGB1-dependent manner. These effects were confirmed in ECs and smooth muscle cells isolated from pulmonary arteries of patients with idiopathic PH. HIMF/HMGB1/RAGE-mediated autophagy and BMPR2 impairment were also observed in pulmonary artery (vascular) smooth muscle cells of hypoxic mice, effects perhaps related to FoxO1 (forkhead box O1) dampening by HIMF. Experiments in EC-specific hResistin-overexpressing transgenic mice confirmed that EC-derived HMGB1 mediated the hResistin-driven pulmonary vascular remodeling and PH.In HIMF-induced PH, HMGB1-RAGE signaling is pivotal for mediating EC-smooth muscle cell crosstalk. The humanized mouse data further support clinical implications for the HIMF/HMGB1 signaling axis and indicate that hResistin and its downstream pathway may constitute targets for the development of novel anti-PH therapeutics in humans.

Propylene glycol is a rarely reported toxicity from high-dose administration of certain intravenous drugs, including lorazepam and pentobarbital. We present a case of iatrogenic propylene glycol toxicity secondary to a high-dose pentobarbital infusion for the treatment of refractory intracranial hypertension due to cerebral venous sinus thrombosis. The patient developed metabolic acidosis and acute kidney failure secondary to propylene glycol toxicity. After initiation of continuous renal replacement therapy, the patient’s acute renal failure and lactic acidosis resolved. Using the Naranjo scale, this case received a score of 5, defining it as a “probable” adverse drug event. In patients who develop lactic acidosis and acute renal failure after initiation of high-dose pentobarbital, propylene glycol toxicity should be higher up in the differential diagnosis. Monitoring the serum osmolality while on pentobarbital could help provide valuable information to prevent iatrogenic propylene glycol toxicity.

Studies have confirmed that optic disc haemorrhage (ODH) is a significant risk factor for the development and progression of primary open-angle glaucoma (POAG). Various populations have differing risk factors for developing POAG. As such, a literature review was conducted examining seven studies published in India, China, Japan, Australia, Korea and the USA. The goal of this review was to better identify ODH risk factors and their relationship to development and progression of POAG. Ultimately, patients with ODH have a greater risk for developing POAG across all populations analysed in this review. However, some populations demonstrated additional risk factors for ODH, such as increasing age and female gender. Paradoxically, data from several studies show that people of African descent have a reduced risk of ODH despite having increased risk of open-angle glaucoma than their Caucasian counterparts. By parsing out the complex relations between ODH and open-angle glaucoma stratified by age, gender and race, we may gain a broader understanding of glaucoma pathogenesis and derive individualised treatment strategies.

Objective To describe contemporary management and outcomes of patients experiencing postoperative hemorrhage after minimally invasive radical prostatectomy. Materials and Methods We retrospectively analyzed data from patients who underwent minimally invasive radical prostatectomy at our institution between January 2010 and January 2017. Clinically significant hemorrhage was defined as a decrease in hemoglobin of ≥30% or 4 g/dL from preoperative to 4 or 14 hours postoperative measurement, receiving a blood transfusion within 30 days, or undergoing a secondary procedure to control bleeding. Patients were analyzed in 3 groups: (1) serially monitored only, (2) received a blood transfusion, and (3) underwent a secondary procedure. Outcomes included imaging studies performed, length of stay, emergency room visits, hospital readmissions, complication rates, and functional outcomes. Results Of 3749 men, 4% (151/3749) had clinically significant hemorrhage, 1.6% (60/3749) received a transfusion; 0.32% (12/3749) underwent a secondary procedure to control bleeding. In a 30-day composite outcome, increased healthcare utilization (emergency room visit, readmission, or Grade ≥3 complications), was seen in 25% of the serial monitoring group, 65% of the transfusion group, and 100% in the secondary procedure group. This rate in 3598 men without hemorrhage was 12.5%. One-year erectile function was poorest in men who underwent a secondary procedure. Urinary functional outcomes were similar in the 3 groups. Conclusion Most patients experiencing clinically significant hemorrhage will stabilize without transfusion, and a very small fraction require secondary intervention. Patients experiencing milder bleeding events utilized additional healthcare resources at approximately twice the rate of those who did not, warranting appropriate counseling and postoperative monitoring.

Enantioselective total syntheses of the anticancer isocarbostyril alkaloids (+)-7-deoxypancratistatin, (+)-pancratistatin, (+)-lycoricidine, and (+)-narciclasine are described. Our strategy for accessing this unique class of natural products is based on the development of a Ni-catalyzed dearomative trans-1,2-carboamination of benzene. The effectiveness of this dearomatization approach is notable, as only two additional olefin functionalizations are needed to construct the fully decorated aminocyclitol cores of these alkaloids. Installation of the lactam ring has been achieved through several pathways and a direct interconversion between natural products was established via a late-stage C-7 cupration. Using this synthetic blueprint, we were able to produce natural products on a gram scale and provide tailored analogs with improved activity, solubility, and metabolic stability.

Objective— Pulmonary hypertension (PH) is characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown that in rodents, hypoxia-induced mitogenic factor (HIMF; also known as FIZZ1 or resistin-like molecule-β) causes PH by initiating lung vascular inflammation. We hypothesized that hypoxia-inducible factor-1 (HIF-1) is a critical downstream signal mediator of HIMF during PH development. Approach and Results— In this study, we compared the degree of HIMF-induced pulmonary vascular remodeling and PH development in wild-type (HIF-1α +/+ ) and HIF-1α heterozygous null (HIF-1α +/− ) mice. HIMF-induced PH was significantly diminished in HIF-1α +/− mice and was accompanied by a dysregulated vascular endothelial growth factor-A–vascular endothelial growth factor receptor 2 pathway. HIF-1α was critical for bone marrow–derived cell migration and vascular tube formation in response to HIMF. Furthermore, HIMF and its human homolog, resistin-like molecule-β, significantly increased interleukin (IL)-6 in macrophages and lung resident cells through a mechanism dependent on HIF-1α and, at least to some extent, on nuclear factor κB. Conclusions— Our results suggest that HIF-1α is a critical downstream transcription factor for HIMF-induced pulmonary vascular remodeling and PH development. Importantly, both HIMF and human resistin-like molecule-β significantly increased IL-6 in lung resident cells and increased perivascular accumulation of IL-6–expressing macrophages in the lungs of mice. These data suggest that HIMF can induce HIF-1, vascular endothelial growth factor-A, and interleukin-6, which are critical mediators of both hypoxic inflammation and PH pathophysiology.

Identification and analysis of synthetic cannabinoids (SCs) in biological specimens remains an ongoing challenge for forensic toxicologists. Analytical method development is both resource and time consuming, and falls behind the illicit production of newer SCs. Distinguishing optimal metabolic targets and specific SC use is further complicated by metabolic pathway convergence between different SCs. Gaining further insight into the prevalence and psychopharmacologic role of these drugs in forensic cases, particularly in individuals suspected of driving impaired, is important. The prevalence of SC metabolites (SCMs) in suspects of impaired driving in Washington, DC between June 2012 and August 2013 was studied. A total of 526 urine samples were screened for 12 SCMs by liquid chromatography tandem mass spectrometry in separate duplicate analyses. Nineteen cases (3.6%) confirmed positive for the following SCMs: UR-144 N-pentanoic acid (n = 17;89%), JWH-073 butanoic acid (n = 3;16%), JWH-018 pentanoic acid (n = 3;16%), AM-2201 4-hydroxypentyl (n = 3;16%) and 5-fluoro PB22 3-carboxyindole (n = 1;5%). This study made use of existing analytical methodology to provide insight into the prevalence of synthetic cannabinoid use in DUID cases. Understanding the range and extent of use in these cases can provide valuable information to the forensic community.

This cohort study assesses the association of race/ethnicity with overall survival among patients with colorectal liver metastasis overall and among those undergoing liver resection.

Purpose: To compare clinical response of intermittent bolus versus continuous infusion neostigmine for acute colonic pseudo-obstruction (ACPO). Acute colonic pseudo-obstruction occurs due to reduced colonic parasympathetic activity. Neostigmine is an acetylcholinesterase inhibitor that increases frequency of smooth muscle contraction by increasing acetylcholine at autonomic nervous system synapses. Although these administration modalities have been studied separately, they have never been compared. Methods: This retrospective study compared bolus versus continuous infusion neostigmine for ACPO. The primary outcome was initial clinical response, defined as bowel movement (BM) within 4 hours of bolus dose or 24 hours of initiation of continuous infusion. Secondary outcomes included time to BM, bowel diameter reduction at 24 hours, incidence of bradycardia, additional neostigmine requirements, and need for colonic decompression or surgical intervention. Results: Seventy-five patients were included (bolus n = 37; infusion n = 38). Median total 24-hour neostigmine dose was 2.0 mg (interquartile range [IQR]: 2.0-2.6) with bolus and 9.6 mg (IQR: 6.3-9.6) with continuous infusion. Initial clinical response was similar (infusion 81.6% vs bolus 62.2%, P = .06), but continuous infusion was associated with greater bowel diameter reduction (73.7% vs 40.5%, P = .004). Bolus administration had shorter time to BM (1.4 vs 3.5 hours, P = .0478) and increased need for colonic decompression (67.6% vs 39.5%, P = .0148). Bolus dosing was associated with less bradycardia (13.5% vs 39.5%, P = 0.011), with no difference in atropine usage (10.8% vs 5.3%, P = .43). Conclusion: Initial clinical response was similar between groups; however, continuous infusion neostigmine was associated with greater bowel diameter reduction at 24 hours. Bolus administration resulted in less bradycardia; however, given the lack of difference in atropine use, clinical significance is unknown. This study is the first to compare bolus versus continuous infusion neostigmine for ACPO. Further studies are needed to confirm findings.

PURPOSE: To our knowledge the ideal methodology of quantifying secondary Gleason pattern 4 in men with Grade Group 2/Gleason score 3 + 4 = 7 on biopsy remains unknown. We compared various methods of Gleason pattern 4 quantification and evaluated associations with adverse pathology findings at radical prostatectomy. MATERIALS AND METHODS: A total of 457 men with Grade Group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy at our institution. Only patients with 12 or more reviewed cores were included in analysis. We evaluated 3 methods of quantifying Gleason pattern 4, including the maximum percent of Gleason pattern 4 in any single core, the overall percent of Gleason pattern 4 (Gleason pattern 4 mm/total cancer mm) and the total length of Gleason pattern 4 in mm across all cores. Adverse pathology features at radical prostatectomy were defined as Gleason score 4 + 3 = 7 or greater (Grade Group 3 or greater), and any extraprostatic extension, seminal vesical invasion and/or lymph node metastasis. A training/test set approach and multivariable logistic regression were used to determine whether Gleason pattern 4 quantification methods could aid in predicting adverse pathology. RESULTS: On multivariable analysis all Gleason pattern 4 quantification methods were significantly associated with an increased risk of adverse pathology (p

BACKGROUND: Surgical training has long been to “never let the sun set on a bowel obstruction” without an operation to rule out and/or treat compromised bowel. However, advances in diagnostics have called into question the appropriate timing of non-emergent operations and expectant management is increasingly used. We performed a systematic review to evaluate the safety and effectiveness of expectant management for adhesive small bowel obstruction (aSBO) compared to early, non-emergent operation. MATERIALS & METHODS: We queried PubMed, EMBASE, and Cochrane databases for studies (1990–present) comparing early, nonemergent operations and expectant management for aSBO (PROSPERO #CRD42017057676). RESULTS: Of 4873 studies, 29 cohort studies were included for full-text review. Four studies directly compared early surgery with expectant management, but none excluded patients who underwent emergent operations from those having early non-emergent surgery, precluding a direct comparison of the two treatment types of interest. When aggregated, the rate of bowel resection was 29% in patients undergoing early operation vs. 10% in those undergoing expectant management. The rate of successful, nonoperative management in the expectant group was 58%. There was a 1.3-day difference in LOS favoring expectant management (LOS 9.7 vs. 8.4 days), and the rate of death was 2% in both groups. CONCLUSION: Despite the shift towards expectant management of aSBO, no published studies have yet compared early, nonemergent operation and expectant management. A major limitation in evaluating the outcomes of these approaches using existing studies is confounding by indication related to including patients with emergent indications for surgery on admission in the early operative group. A future study, randomizing patients to early non-emergent surgery or expectant management, should inform the comparative safety and value of these approaches.

Background One in 5 patients with completely resected early-stage non-small cell lung cancer will recur within 2 years. Risk stratification may facilitate a personalized approach to the use of adjuvant therapy and surveillance imaging. We developed a prediction model for recurrence based on five clinical variables (tumor size and grade, visceral pleural and lymphovascular invasion, and sublobar resection), and tested the hypothesis that the addition of several new molecular markers of poor long-term outcome (vascular endothelial growth factor C; microRNA precursors 486 and 30d) would enhance prediction. Methods We performed a retrospective cohort study of patients with completely resected, node-negative non-small cell lung cancer from 2011 to 2014 (follow-up through 2016) using the Lung Cancer Biospecimen Resource Network. Cox regression was used to estimate the 2-year risk of recurrence. Our primary measure of model performance was the optimism-corrected C statistic. Results Among 173 patients (mean tumor size, 3.6 cm; 12% sublobar resection, 32% poorly differentiated, 16% lymphovascular invasion, 26% visceral pleural invasion), the 2-year recurrence rate was 23% (95% confidence interval, 17% to 31%). A prediction model using five known risk factors for recurrence performed only slightly better than chance in predicting recurrence (optimism-corrected C statistic, 0.54; 95% confidence interval, 0.51 to 0.68). The addition of biomarkers did not improve the model's ability to predict recurrence (corrected C statistic, 0.55; 95% confidence interval, 0.52 to 0.71). Conclusions We were unable to predict lung cancer recurrence using a risk-prediction model based on five well-known clinical risk factors and several biomarkers. Further research should consider novel predictors of recurrence to stratify patients with completely resected early-stage non-small cell lung cancer according to their risk of recurrence.

IntroductionPancreaticoduodenectomy is a complex surgical procedure associated with high morbidity and prolonged length of stay. Enhanced recovery after surgery principles have reduced complications rate and length of stay for multiple types of operations. We hypothesized that implementation of a standardized perioperative care pathway would facilitate safe discharge by five days after pancreaticoduodenectomy.MethodsWe performed a retrospective cohort study of patients undergoing pancreaticoduodenectomy 18 months prior to and 18 months following implementation of a perioperative care pathway at a quaternary center performing high volume pancreatic surgery.ResultsA total of 145 patients underwent pancreaticoduodenectomy (mean age 63 ± 10 years, 52% female), 81 before and 64 following pathway implementation, and the groups were similar in terms of preoperative comorbidities. The percentage of patients discharged within 5 days of surgery increased from 36% to 64% following pathway implementation (p = 0.001), with no observed differences in post-operative serious adverse events (p = 0.34), pancreatic fistula grade B or C (p = 0.28 and p = 0.27 respectively), or delayed gastric emptying (p = 0.46). Multivariate regression analysis showed length of stay ≤5 days three times more likely after pathway implementation. Rates of readmission within 30 days (20% pre- vs. 22% post-pathway (p = 0.75)) and 90 days (27% pre- vs. 36% post-pathway (p = 0.27)) were unchanged after pathway implementation, and were no different between patients discharged before or after day 5 at both 30 days (19% ≤5 days vs. 23% ≥ 6 days (p = 0.68)) and 90 days (32% ≤5 days vs. 30% ≥ 6 days (p = 0.81)).ConclusionsStandardizing perioperative care via enhanced recovery protocols for patients undergoing pancreaticoduodenectomy facilitates safe discharge by post-operative day five.

Introduction Spinal cord stimulation (SCS) devices are cost effective and improve function as well as quality of life. Despite the demonstrated benefits of SCS, some patients have the device explanted. We are interested in exploring the patient characteristics of those explanted. Methods This is a retrospective chart review of neurostimulation patients who underwent explantation at 18 centers across the United States within the previous five years. Results Data from 352 patients were collected and compiled. Failed Back Surgery syndrome was the most common diagnosis (38.9%; n = 136/350) and over half of the patients reported numerical rating scale (NRS) scores ≥8 prior to implant (64.3%; n = 207/322). All patients reported changes in NRS scores across time, with an initial decrease after implant followed by a pre-explant increase (F (2, 961) = 121.7, p

Background Historical training instructs surgeons to, “never let the sun set on a small bowel obstruction (SBO)” due to concern for bowel ischemia. However, the routine use of computed tomography scans for ruling out ischemia provides the opportunity for trial of nonoperative management, allowing time for resolution of adhesive SBO. In light of advances in practice, little is known about how surgeons manage these patients, in particular, whether there is consistency in the stated duration for safe nonoperative management. Methods Using a case vignette (a patient with computed tomography scan diagnosed complete SBO without bowel ischemia), we interviewed a purposive sample of general surgeons practicing in Washington State to understand stated approaches to clinical management. Interview questions addressed typical practice, preferred timing of surgery, and approach. We conducted a content analysis to understand current practice and attitudes. Results We interviewed 15 surgeons practicing across Washington State. Surgical practice patterns for patients with SBO varied widely. The period of time that surgeons were willing to manage patients nonoperatively ranged from 1-7 d. Interviews revealed insight into surgical decision-making, the importance of patient preferences, variation in practice, and evidence gaps. All surgeons acknowledged a lack of evidence to support appropriate management of patients with SBO. Conclusions Interviews with practicing surgeons highlight a changing paradigm away from routine early surgery for patients with adhesive SBO. However, there is lack of consensus in the appropriate duration of nonoperative management and practices vary considerably. These revealed attitudes inform the feasibility and design of future randomized studies of patients with adhesive SBO.

Background The benefits of minimally invasive surgery (MIS) for low-risk or minor liver resection are well established. There is growing interest in MIS for major hepatectomy (MH) and other challenging resections, but there remain unanswered questions of safety that prevent broad adoption of this technique. Study Design We conducted a retrospective cohort study of patients undergoing hepatectomy at 65 hospitals participating in the NSQIP Hepatopancreatobiliary Collaborative in 2014. We assessed serious morbidity or mortality (SMM; including organ/space infection and organ failure). Secondary outcomes included transfusion, bile leak, liver failure, reoperation or intervention, and 30-day readmission. We also measured factors considered to make resection more challenging (ie large tumors, cirrhosis, ≥3 concurrent resections, previous neoadjuvant chemotherapy, and morbid obesity). Results There were 2,819 patients who underwent hepatectomy (aged 58 ± 14 years; 53% female; 25% had MIS). After adjusting for clinical and operative factors, the odds of SMM (odds ratio [OR] = 0.57; 95% CI 0.34 to 0.96; p = 0.03) and reoperation or intervention (OR = 0.52; 95% CI 0.29 to 0.93; p = 0.03) were significantly lower for patients undergoing MIS compared with open. In the MH group (n = 1,015 [13% MIS]), there was no difference in the odds of SMM after MIS (OR = 0.37; 95% CI 0.13 to 1.11; p = 0.08); however, minimally invasive MH met criteria for noninferiority. There were no differences in liver-specific complications or readmission between the groups. Odds of SMM were significantly lower after MIS among patients who had received neoadjuvant chemotherapy (OR = 0.33; 95% CI 0.15 to 0.70; p = 0.004). Conclusions In this large study of minimally invasive MH, we found safety outcomes that are equivalent or superior to conventional open surgery. Although the decision to offer MIS might be influenced by factors not included in this evaluation (eg surgeon experience and other patient factors), these findings support its current use in MH.