Lymphovascular Invasion is an Independent Negative Prognostic Factor in Esophageal Adenocarcinoma.

BACKGROUND: The significance of lymphovascular invasion (LVI) in esophageal adenocarcinoma (EAC) has not yet been described. Potential utility as an adjunct to current staging guidelines remains unknown. METHODS: The National Cancer Database was queried from 2006 to 2020. Univariate and multivariable models, Kaplan Meier method, and log-rank test were used. Subgroup analyses by pN stage were conducted. RESULTS: Of 9,689 patients, 23.2% had LVI. LVI was an independent prognostic factor (hazard ratio [HR] 1.401, 95% confidence interval [CI] 1.307-1.502, p < 0.0001) with reduction in median survival to 20.0 months (95% CI 18.9-21.4) from 39.7 months (95% CI 37.8-42.3, p < 0.0001). Multivariable survival analysis adjusted on pN and pT stage found that patients with LVI had decreased survival in a given pN stage (p < 0.001). pN0/LVI+ patients had a similar prognosis to the higher staged pN1/LVI- (28.6 months), although pN1/LVI- patients did slightly worse (p = 0.0135). Additionally, patients with pN1/LVI+ had equivalent survival compared with pN2/LVI- (p = 0.178) as did pN2/LVI+ patients compared with pN3/LVI- (p = 0.995). CONCLUSIONS: In these data, LVI is an independent negative prognostic factor in EAC. LVI was associated with a survival reduction similar to an upstaged nodal status irrespective of T stage. Patients with LVI may be better classified at a higher pN stage.

Complete pathologic response in esophageal adenocarcinoma: does it make a difference?

Advancements in neoadjuvant regimens for esophageal adenocarcinoma have enabled some patients to achieve complete pathologic response at time of esophagectomy. There are currently limited data detailing this trend or the implications of complete pathologic response on survival. The National Cancer Database was used to identify 16,169 patients with esophageal adenocarcinoma that received trimodal therapy including esophagectomy between 2006 and 2020. Of these, 11.4% had complete pathologic response at esophagectomy. Patient factors, staging characteristics, and survival trends were evaluated. In patients diagnosed between 2016 and 2020, the rate of complete pathologic response was 17.5%. Female sex (OR 1.295, 95% CI 1.134-1.481, p = 0.0001), Black race (OR 1.729, 95% CI 1.362-2.196, p = 0.0002), Hispanic ethnicity (OR 1.418, 95% CI 1.073-1.875, p = 0.0141), and later era of diagnosis (2016-2020 OR 2.898, 95% CI 2.508-3.349, p < 0.0001) were independent predictors of complete pathologic response. Clinical stage II disease was associated with an increased probability of complete pathologic response (OR 1.492, 95% CI 1.19-1.871) while clinical stage III disease had a decreased probability of complete pathologic response (OR 0.762, 95% CI 0.621-0.936, p < 0.0001). Complete pathologic response conveyed a strong survival benefit, with a median survival of 86.4 months (95% CI 73.9-102.1) versus 30.7 months (95% CI 29.8-31.7, p < 0.0001) in those without complete pathologic response. Four-year median survival was also higher in those with complete pathologic response (63.3%, 95% CI 60.8-66.0% vs. 39.2%, 95% CI 38.4-40.1%, p < 0.0001). In summary, complete pathologic response is associated with a profound survival advantage in patients with esophageal adenocarcinoma. Such knowledge carries implications for patient counseling, prognostication, and surveillance and demonstrates a need for improved identification of complete clinical response prior to esophagectomy.

GFR estimated with creatinine rather than cystatin C is more reflective of the true risk of adverse outcomes with low GFR in kidney transplant recipients.

BACKGROUND: Serum cystatin C-based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine-based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients. METHODS: Consecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors. RESULTS: There were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8 ml/min/1.73 m2 and a median follow-up of 6 years. Each 10 ml/min/1.73 m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure [hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P < .001 for all) and CV events or mortality outcome (HR 1.28, 1.19 and 1.43, respectively; P < .001 for all). After adjusting for mGFR, eGFRcys associated with graft failure (HR 1.57, P < .001) and CV events or mortality (HR 1.49, P < .001), but eGFRcr did not associate with either. After further adjusting for CV risk factors, risk of these outcomes with lower eGFRcys was attenuated. CONCLUSION: eGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.

Outcomes of asymptomatic histologic pyelonephritis of kidney transplant.

BACKGROUND: Urinary Tract Infections are the most common post-transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy. METHODS: The study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant. RESULTS: The mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3-2.7, diabetes mellitus (OR 2.479, 1.687-3.645), and deceased donation (OR 1.69, 1.098-2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06-3.35), p = .0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36-6.02) and a trend toward higher rejection risk. CONCLUSION: Asymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.

The impact of resilience on headache disability as measured by the Migraine Disability Assessment (MIDAS).

OBJECTIVE: Our objectives were to examine cross-sectional correlations of headache disability with measures of resilience, anxiety, and depression, and to determine if resilience modified the association between headache severity/frequency and disability. BACKGROUND: Resilience is associated with quality of life and functioning among patients with chronic conditions. We investigated whether resilience strongly mitigates headache-related disability as measured by the Migraine Disability Assessment (MIDAS). METHODS: We prospectively recruited 160 patients with primary headache disorders seen in a tertiary headache medicine program between February 20, 2018 and August 2, 2019. Each participant completed the MIDAS, Conner Davidson Resilience Scale (CDRS-25), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and WHO-5 Well-Being Index. RESULTS: The CDRS-25 score was negatively correlated with the total MIDAS (r = -0.21, p = 0.009), GAD-7 (r = -0.56, p < 0.001), and PHQ-9 scores (r = -0.34, p < 0.001). Well-being inversely correlated with disability (r = -0.37, p < 0.001). Increases in anxiety and depression increased the odds of disability. A 1 point increase in the CDRS-25 score decreased the odds of being severely disabled by 4% (OR = 0.96, 95% CI: 0.94 to 0.99, p = 0.001). However, the CDRS-25 score did not significantly moderate the association between headache days and disability. CONCLUSION: Traits associated with resilience decreased the odds of severe disability from headaches, whereas anxiety, depression, and headache frequency were strongly associated with higher disability from headache.

Semi-supervised exercise training program more effective for individuals with postural orthostatic tachycardia syndrome in randomized controlled trial.

PURPOSE: Exercise like any medication requires the correct dose; to be effective the appropriate frequency, duration, and intensity are necessary. This study aimed to assess if a semi-supervised exercise training (ET) program would be more effective at improving aerobic fitness (VO2PEAK), exercise tolerance, and symptoms in individuals with postural orthostatic tachycardia syndrome (POTS) compared to the standard of care (SOC). METHODS: Subjects were randomized to either the ET or SOC groups (n 26 vs. 23; age 33 ± 11 vs. 37 ± 10 years; VO2PEAK 66 ± 15 vs. 62 ± 15% predicted, ET vs. SOC respectively, p > 0.05). Composite Autonomic Symptom Score (COMPASS 31), 10 min stand test, and cardiopulmonary exercise test were performed at baseline and following 12 weeks. The ET group received an exercise consultation and eight semi-supervised in-person or virtual exercise sessions. RESULTS: The ET group demonstrated a greater improvement in VO2PEAK, higher or longer tolerance for baseline peak workload, and more often had a delayed symptom onset with exercise than the SOC group (ΔVO2PEAK 3.4 vs. - 0.2 mL/min/kg, p < 0.0001, ΔWorkload 19 ± 17 vs. 0 ± 10 W; Workload time 63 ± 29 vs. 22 ± 30 s; onset-delay 80% vs. 30%, p < 0.05). Individuals in the ET group reported a significant improvement in orthostatic intolerance domain score (p = 0.02), but there was not a significant difference in the improvement in total COMPASS score (- 11.38 vs. - 6.49, p = 0.09). CONCLUSION: Exercise training was more effective with greater improvements in aerobic fitness, orthostatic symptoms, and exercise tolerance for individuals with POTS when intensity and progression were personalized and delivered with minimal supervision compared to the SOC.

Evaluation of a Novel Wellness Curriculum on Medical Student Wellbeing and Engagement Demonstrates a Need for Student-Driven Wellness Programming.

PROBLEM: Medical training is stressful and has well-established implications for student wellbeing. Despite widespread efforts to reduce student burnout through wellness programming in medical schools, there is a paucity of literature examining students' perception of wellness and engagement with these programs. As such, we sought to evaluate: 1) medical students' level of engagement with a multifaceted wellness curriculum, 2) factors students perceived as important to wellbeing, and 3) associations with longitudinal measures of wellbeing and perceived stress. Intervention: A multipronged wellness curriculum was instituted at Mayo Clinic Alix School of Medicine-AZ (MCASOM-AZ) in 2017. This includes mental health services, curriculum-embedded seminars, wellness committee (composed of students, faculty, and administration) driven programming, and student proposed wellness activities that are reviewed and funded by the committee. The authors invited students at our institution to complete questionnaires at three timepoints during the 2018-2019 academic year. Questionnaires asked participants to rank eight factors from least to most important to their overall wellbeing. Participants self-reported their participation in each prong of the wellness curriculum and ranked the impact of each on their overall wellbeing. Their wellbeing and perceived stress were measured at each timepoint using validated psychological instruments. Context: As MCASOM-AZ opened in 2017, the student body at the time of study consisted of first- and second-year medical students. All students had the opportunity to engage with all aspects of the wellness curriculum and participate in this study, however participation was elective and all responses were anonymous. Of the MCASOM-AZ student body comprised of 100 students, 58 consented to participate in the study, 41.4% of which were Year 1 and 58.6% of which were Year 2 students. Participant age and gender were collected and were representative of the larger student body. Impact: Students engaged most with student-initiated wellness. They perceived unscheduled time as most impactful to their overall wellbeing with student-initiated activities as second-most impactful. Students with higher perceived stress were more likely than others to use mental health resources, which otherwise ranked lower in importance. Ranking academic performance as important to wellbeing was associated with higher wellbeing. There was no difference in wellbeing between students who participated in the wellness curriculum and those who did not. However, overall student wellbeing increased over the course of the year while perceived stress decreased. Lessons Learned: Medical school programs may benefit from allowing students to direct or contribute to the design of their own wellness curriculum. Additionally, medical education should work toward creating a more supportive learning environment with improved flexibility in order to better meet students' individual needs without compromising their education. Despite having low utilization rates overall, mental health resources remain an important aspect of student support services as they are used by students under greater amounts of perceived stress than their peers.Supplemental data for this article is available online at https://doi.org/10.1080/10401334.2021.2004415 .

VO2peak prior to transplant differentiates survival post kidney transplant.

The OPTN/UNOS utilizes the calculated estimated posttransplant survival (EPTS) score as the measure of post-kidney transplant survival to guide allocation of deceased donor kidney transplantation. This score does not include any metric of functional capacity. Peak oxygen uptake (VO2peak ), is an established predictor of survival among both the general and diseased populations. We assessed the association and discriminative capacity of VO2peak and that of EPTS score and all-cause mortality post-kidney transplant. Additionally, we assessed the "mortality risk" lower VO2peak conferred on those patients with low EPTS score. Among a cohort of 293 transplant recipients with at least 3-years post-transplant follow-up, the median VO2peak was 15.0 ml/Kg/min. Lower pre-transplant VO2peak and higher EPTS score conferred higher risk of post-transplant mortality. Among the cohort of "low-risk" patients (patients with EPTS score < 50) those with lower VO2peak had significantly higher risk of mortality (log rank p = 0.045). In fact, the mortality risk among those with low-EPTS (< 50) and low VO2peak  < 12 ml/Kg/min was equivalent to those with high EPTS (> 80) score. We concluded functional capacity as defined by VO2peak is an important reflection of post-transplant survival. VO2peak is able to identify those with low EPTS who have similar survival to that of high EPTS phenotype.

Histopathologic features of necrobiosis lipoidica.

BACKGROUND: Necrobiosis lipoidica (NL) is an uncommon granulomatous dermatosis that can occur in patients with or without associated diabetes mellitus (DM). Prior studies have attempted to determine distinctive histopathologic features of NL in patients with and without DM. METHODS: A retrospective review of 97 patients with NL was performed to determine the similar and distinctive histopathologic features in patients with DM and without DM. RESULTS: Of the 97 patients, 32% (n = 31) had DM. Epidermal acanthosis was seen more commonly in diabetics than nondiabetics (32.3% vs. 12.1%; p = 0.017). Naked (sarcoidal/tuberculoid) granulomas were more frequently observed in nondiabetics than diabetics (22.7% vs. 3.2%; p = 0.016). Eosinophils were more common in nondiabetics than diabetics (38.5% vs. 9.7%; p = 0.004), while neutrophilic infiltration was more common in diabetics than nondiabetics (45.2% vs. 17.5%; p = 0.004). CONCLUSIONS: This study corroborates well-documented histopathologic features of NL and shows distinctive histopathologic features of NL among patients with DM-I, DM-II, and without DM. These results support the hypothesis that there are different underlying drivers of NL between diabetics and nondiabetics.

Duration of delayed graft function and its impact on graft outcomes in deceased donor kidney transplantation.

BACKGROUND: There is controversy regarding the impact of delayed graft function (DGF) on kidney transplant outcomes. We hypothesize that the duration of DGF, rather than DGF itself, is associated with long-term kidney graft function. METHODS: We analyzed all deceased donor kidney transplants (DDKT) done at our center between 2008 to 2020. We determined factors associated with DGF duration. DGF duration was assessed at three 14-day intervals: < 14 DGF days, 14-27 DGF days, > 28 DGF days. We studied the impact of DGF duration on survival and graft function and resource utilization, including hospital length of stay and readmissions. RESULTS: 1714 DDKT recipients were included, 59.4% (n = 1018) had DGF. The median DGF duration was 10 days IQR (6,15). The majority of recipients (95%) had resolution of DGF within 28 days. Donor factors associated with DGF days were longer cold ischemia time, donor on inotropes, older age, donation after circulatory death, higher terminal creatinine, and hypertension. Recipient factors associated with increased DGF duration included male sex, length on dialysis before transplant, and higher body mass index. There were no differences in acute rejection events or interstitial fibrosis progression by 4 months when comparing DGF days. The median length of stay was 3 days. However, readmissions increased with increasing DGF duration. Death-censored graft survival was not associated with the length of DGF except when DGF lasted > 28 days. CONCLUSIONS: Inferior graft survival was observed only in recipients of DDKT with DGF lasting beyond 28 days. DGF lasting < 28 days had no impact on graft survival. Duration of DGF, rather than DGF itself, is associated with graft survival. TRIAL REGISTRATION: Retrospective study approved by Mayo Clinic IRB number ID: 20-011561.

A Framework for Revisiting Brain Death: Evaluating Awareness and Attitudes Toward the Neuroscientific and Ethical Debate Around the American Academy of Neurology Brain Death Criteria.

BACKGROUND: There remains a lack of awareness around the American Academy of Neurology (AAN) procedural criteria for brain death and the surrounding controversies, leading to significant practice variability. This survey study assessed for existing knowledge and attitude among healthcare professionals regarding procedural criteria and potential change after an educational intervention. METHODS: Healthcare professionals with increased exposure to brain injury at Mayo Clinic hospitals in Arizona and Florida were invited to complete an online survey consisting of 2 iterations of a 14-item questionnaire, taken before and after a 30-minute video educational intervention. The questionnaire gathered participants' opinion of (1) their knowledge of the AAN procedural criteria, (2) whether these criteria determine complete, irreversible cessation of brain function, and (3) on what concept of death they base the equivalence of brain death to biological death. RESULTS: Of the 928 people contacted, a total of 118 and 62 participants completed the pre-intervention and post-intervention questionnaire, respectively. The results show broad, unchanging support for the concept of brain death (86.8%) and that current criteria constitute best practice. While 64.9% agree further that the loss of consciousness and spontaneous breathing is sufficient for death, contradictorily, 37.6% believe the loss of additional integrated bodily functions such as fighting infection is necessary for death. A plurality trusts these criteria to demonstrate loss of brain function that is irreversible (67.6%) and complete (43.6%) at baseline, but there is significantly less agreement on both at post-intervention. CONCLUSION: Although there is consistent support that AAN procedural criteria are best for clinical practice, results show a tenuous belief that these criteria determine irreversible and complete loss of all brain function. Despite support for the concept of brain death first developed by the President's Council, participants demonstrate confusion over whether the loss of consciousness and spontaneous breath are truly sufficient for death.

Prognostic Utility of Daily Changes in Glasgow Coma Scale and the Full Outline of Unresponsiveness Score Measurement in Patients with Metabolic Encephalopathy, Central Nervous System Infections and Stroke in Uganda.

BACKGROUND: Metabolic encephalopathy (ME), central nervous system (CNS) infections, and stroke are common causes of reduced level of consciousness in Uganda. However, the prognostic utility of changes in the daily measurements of the Full Outline of Unresponsiveness (FOUR) score and Glasgow Coma Scale (GCS) score in these specific disorders is not known. METHODS: We conducted secondary analyses of data from patients who presented with reduced level of consciousness due to CNS infections, stroke, or ME to a tertiary hospital in Uganda. Patients had FOUR/GCS scores at admission and at 24 and 48 h. We calculated a change in FOUR score (ΔFOUR) and change in GCS score (ΔGCS) at 24 and 48 h and used logistic regression models to determine whether these changes were predictive of 30-day mortality. In addition, we determined the prognostic utility of adding the admission score to the 24-h ΔFOUR and 24-h ΔGCS on mortality. RESULTS: We analyzed data from 230 patients (86 with ME, 79 with CNS infections, and 65 with stroke). The mean (SD) age was 50.8 (21.3) years, 27% (61 of 230) had HIV infection, and 62% (134 of 230) were peasant farmers. ΔFOUR at 24 h was predictive of mortality among those with ME (odds ratio [OR] 0.64 [95% confidence interval {CI} 0.48-0.84]; p = 0.001) and those with CNS infections (OR 0.65 [95% CI 0.48-0.87]; p = 0.004) but not in those with stroke (OR 1.0 [95% CI 0.73-1.38]; p = 0.998). However, ΔGCS at 24 h was only predictive of mortality in the ME group (OR 0.69 [95% CI 0.56-0.86]; p = 0.001) and not in the CNS or stroke group. This 24-h ΔGCS and ΔFOUR pattern was similar at 48 h in all subgroups. The addition of an admission score to either 24-h ΔFOUR or 24-h ΔGCS significantly improved the predictive ability of the scores in those with stroke and CNS infection but not in those with ME. CONCLUSIONS: Twenty-four-hour and 48-h ΔFOUR and ΔGCS are predictive of mortality in Ugandan patients with CNS infections and ME but not in those with stroke. For individuals with stroke, the admission score plays a more significant predictive role that the change in scores.

Radial artery access is under-utilized in women undergoing PCI despite potential benefits: Mayo Clinic PCI Registry.

BACKGROUND: Women may benefit from radial artery access (RAA) for percutaneous coronary interventions (PCI) due to a higher risk of bleeding compared to men; however, RAA may be underutilized in women. We sought to determine the frequency and predictors of RAA use in patients undergoing PCI. METHODS: We studied 21,123 (29.0% female) participants in the Mayo Clinic PCI Registry from January 1, 2006-December 31, 2016. Data were analyzed as a cohort and by time tertiles. Frequency of RAA versus femoral access and bleeding events were recorded. Logistic regression was used to identify predictors of RAA. RESULTS: In the overall cohort, women compared to men were older (69.6 ± 12.6 vs. 65.6 ± 11.9; p < .001), more likely to present with acute coronary syndrome (82.0% in women vs. 80.0% in men; p = .0008) and had more comorbidities. RAA increased from tertile one (3.5% for women vs. 4.0% for men; p = .3) through tertile three (46.8% for women vs. 50.3% for men; p = .01), but remained lower in women. In multivariable analysis, female sex is associated with 22% less RAA use (OR 0.78, 95% CI 0.72-0.84; p < .0001). Women compared to men experienced more bleeding (6.3 vs. 3.0%; p < .0001) but bleeding was less likely in RAA (OR 0.45, 95% CI 0.36-0.56; p < .0001). CONCLUSION: Women undergoing PCI are less likely to receive RAA compared to men despite having a higher risk of bleeding. This trend persists despite increase in RAA use. Given the potential benefit of RAA in women, sex should be considered in patient selection for RAA.

Current Practices for Screening and Management of Financial Distress at NCCN Member Institutions.

BACKGROUND: Financial distress from medical treatment is an increasing concern. Healthcare organizations may have different levels of organizational commitment, existing programs, and expected outcomes of screening and management of patient financial distress. PATIENTS AND METHODS: In November 2018, representatives from 17 (63%) of the 27 existing NCCN Member Institutions completed an online survey. The survey focused on screening and management practices for patient financial distress, perceived barriers in implementation, and leadership attitudes about such practices. Due to the lack of a validated questionnaire in this area, survey questions were generated after a comprehensive literature search and discussions among the study team, including NCCN Best Practices Committee representatives. RESULTS: Responses showed that 76% of centers routinely screened for financial distress, mostly with social worker assessment (94%), and that 56% screened patients multiple times. All centers offered programs to help with drug costs, meal or gas vouchers, and payment plans. Charity care was provided by 100% of the large centers (≥10,000 unique annual patients) but none of the small centers that responded (<10,000 unique annual patients; P=.008). Metrics to evaluate the impact of financial advocacy services included number of patients assisted, bad debt/charity write-offs, or patient satisfaction surveys. The effectiveness of institutional practices for screening and management of financial distress was reported as poor/very poor by 6% of respondents. Inadequate staffing and resources, limited budget, and lack of reimbursement were potential barriers in the provision of these services. A total of 94% agreed with the need for better integration of financial advocacy into oncology practice. CONCLUSIONS: Three-fourths of NCCN Member Institutions reported screening and management programs for financial distress, although the actual practices and range of services vary. Information from this study can help centers benchmark their performance relative to similar programs and identify best practices in this area.

Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma.

BACKGROUND: Inositol polyphosphate-5-phosphatase (INPP5A) has been shown to play a role in the progression of actinic keratosis to cutaneous squamous cell carcinoma (cSCC) and the progression of localized disease to metastatic disease. Currently, no cSCC biomarkers are able to risk stratify recurrent and metastatic disease. OBJECTIVE: To determine the prognostic value of INPP5A expression in cSCC recurrent and metastatic disease. METHODS: We conducted a multicenter, single-institutional, retrospective cohort study within the Mayo Clinic Health System on the use of immunohistochemical staining to examine cSCC INPP5A protein expression in primary tumors and recurrent and metastatic disease. Dermatologists and dermatopathologists were blinded to outcome. RESULTS: Low staining expression of INPP5A in recurrent and metastatic disease tumors was associated with poor overall survival (OS) (31.0 months for low versus 62.0 months for high expression; P = .0272). A composite risk score (calculated as score of primary tumor + score of recurrent or metastatic disease tumor, with tumors with high expression scoring a zero and low expression a 1, score range 0-2) of 0 was predictive of improved OS compared with a composite risk score of ≥1 (hazard ratio 0.42, 95% confidence interval 0.21-0.84; P = .0113). LIMITATIONS: This is a multicenter but single institution study of a white population. CONCLUSION: Loss of INPP5A expression predicts poor OS in recurrent and metastatic disease of cSCC.

Same-Day Discharge after Vaginal Hysterectomy with Pelvic Floor Reconstruction: Pilot Study.

STUDY OBJECTIVE: To determine the safety and feasibility of same-day discharge (SDD) in patients undergoing vaginal hysterectomy with pelvic floor reconstruction. DESIGN: Prospective cohort pilot study. SETTING: Single academic medical center. PATIENTS: Women undergoing vaginal hysterectomy with pelvic floor reconstruction were considered for inclusion in the study. INTERVENTIONS: SDD or overnight hospitalization after surgery. MEASUREMENTS AND MAIN RESULTS: A total cohort of 55 women undergoing vaginal hysterectomy and pelvic floor reconstruction for pelvic organ prolapse and/or urinary incontinence was identified. The control group consisted of 19 women who were planned for overnight hospitalization. The intervention group had 36 women who were planned for SDD. In the intervention group 63.9% of patients (n = 23) were successfully discharged home and 36.1% (n = 13) required an unplanned overnight admission. Reasons for unplanned admission included persistent anesthetic effects (dizziness/nausea/drowsiness, n = 9, 69%), uncontrolled pain (n = 1, 7.7%), fever (n = 1, 7.7%), anemia (n = 2, 15.4%), with return to operating room for hematoma evacuation (n = 1, 7.7%). A voiding trial was passed on the first attempt in 30 patients (54.5%). The percentage of successful voiding trials on the first attempt was 30.8% for patients requiring unplanned admission and 78.9% for patients with planned overnight hospitalization (p = .011). There were no significant differences in the number of emergency department visits (p = .677) or unplanned office visits (p = .193) between the control and intervention groups. CONCLUSION: SDD after vaginal hysterectomy with pelvic floor reconstruction appears to be safe and feasible. Patients who were discharged the same day did not require a higher volume of emergency department or office evaluations.

A comparison of the Full Outline of Unresponsiveness (FOUR) and Glasgow Coma Scale (GCS) Scores in Predicting Mortality Among Patients with Reduced Level of Consciousness in Uganda.

BACKGROUND: Reduced level of consciousness (LOC) is a common cause of presentation among acutely ill adults in sub-Saharan Africa and is associated with high rates of mortality. Although the Full Outline of Unresponsiveness (FOUR) score is often used in clinical practice, its utility in predicting mortality has not been assessed in the region. METHODS: We prospectively enrolled adults presenting with reduced LOC to Mbarara Regional Referral Hospital in Uganda. We recorded clinical and laboratory data and performed the FOUR and Glasgow Coma Scale (GCS) scores at admission. We used survival analysis, fit Cox proportional hazards regression models to assess the predictive properties of the two scores, and compared their performance using area under the receiver operating characteristic curve (AUROC). RESULTS: We enrolled 359 patients, mean (SD) age was 51 (22.2) years, and 58% (210/359) were male. The median (interquartile range) admission FOUR and GCS scores were 13.0 (3.0-16.0) and 10.0 (3.0-14.0), respectively. Subjects with the FOUR score of 0-11 had a 2.6-fold higher hazard of 30-day mortality (HR 2.6, 95% CI 1.9-3.6, p < 0.001) compared to those with the score of 12-16. Those with the GCS score of 3-8 had a 2.7-fold higher hazard of 30-day mortality (HR 2.7, 95% CI 2.0-3.8, p < 0.001) compared to those with the score of 9-15. The AUROC (95% CI) for the FOUR score and GCS score was 0.68 (0.62-0.73) and 0.67 (0.62-0.73), respectively (p = 0.825). CONCLUSIONS: The FOUR score is comparable to the GCS score in predicting mortality in Uganda. Our findings support the introduction of the FOUR score in guiding the management of patients with reduced LOC in sub-Saharan Africa.

Does location matter? Characterisation of the anatomic locations, molecular profiles, and clinical features of gliomas.

BACKGROUND: Neuroanatomic locations of gliomas may influence clinical presentations, molecular profiles, and patients' prognoses. METHODS: We investigated our institutional cancer registry to include patients with glioma over a 10-year period. Statistical tests were used to compare demographic, genetic, and clinical characteristics among patients with gliomas in different locations. Survival analysis methods were then used to assess associations between location and overall survival in the full cohort, as well as in relevant subgroups. RESULTS: 182 gliomas were identified. Of the tumours confined to a single lobe, there were 51 frontal (28.0%), 50 temporal (27.5%), 22 parietal (12.1%), and seven occipital tumours (3.8%) identified. Tumours affecting the temporal lobe were associated with reduced overall survival when compared to all other tumours (11 months vs. 13 months, log-rank p = 0.0068). In subgroup analyses, this result was significant for males [HR (95%CI) 2.05 (1.30, 3.24), p = 0.002], but not for females [HR (95%CI) 1.12 (0.65, 1.93), p = 0.691]. Out of 82 cases tested for IDH-1, 10 were mutated (5.5%). IDH-1 mutation was present in six frontal, two temporal, one thalamic, and one multifocal tumour. Out of 21 cases tested for 1p19q deletions, 12 were co-deleted, nine of which were frontal lobe tumours. MGMT methylation was assessed in 45 cases; 7/14 frontal tumours and 6/13 temporal tumours were methylated. CONCLUSION: Our results support the hypothesis that the anatomical locations of gliomas influence patients' clinical courses. Temporal lobe tumours were associated with poorer survival, though this association appeared to be driven by these patients' more aggressive tumour profiles and higher risk baseline demographics. Independently, female patients who had temporal lobe tumours fared better than males. Molecular analysis was limited by the low prevalence of genetic testing in the study sample, highlighting the importance of capturing this information for all gliomas. IMPORTANCE OF THIS STUDY: The specific neuroanatomic location of tumours in the brain is thought to be predictive of treatment options and overall prognosis. Despite evidence for the clinical significance of this information, there is relatively little information available regarding the incidence and prevalence of tumours in the different anatomical regions of the brain. This study has more fully characterised tumour prevalence in different regions of the brain. Additionally, we have analysed how this information may affect tumours' molecular characteristics, treatment options offered to patients, and patients' overall survival. This information will be informative both in the clinical setting and in directing future research.

Assessment of Quality of Life following Allogeneic Stem Cell Transplant for Myelofibrosis.

Patient-reported outcomes (PROs) for patients with myelofibrosis (MF) have been well characterized, but little is known about quality of life (QoL) following allogeneic stem cell transplantation (allo-SCT). Medical data and PRO measures were collected before transplant and at day 30, day 100, and 1 year after allo-SCT. PRO measures include Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), Brief Fatigue Inventory, Global Assessment of Change, and Functional Assessment of Cancer Therapy-Bone Marrow Transplant. Forty-four patients who had baseline QoL and at least 1 post-transplant assessment were included. The median age of the patients was 62.5 years (range, 35 to 74 years). At baseline, the mean MPN Total Symptom Score was 28.0, and at day 30, day 100, and 1 year, it was 25.4, 32.3, and 24.3, respectively. However, in myeloproliferative neoplasm-specific symptoms, such as itching, night sweats, bone pain, and fever, a statistically significant improvement was observed for at least 1 time point following transplant. At day 30, 10 (26.3%) patients reported a little/moderately/very much better overall QoL since their transplant, and 26 (68.45%) had a little/moderately/very much worse QoL. At day 100, 10 (30.3%) reported better QoL and 19 (57.6%) reported worsening since transplant. By 1 year, 16 (61.5%) reported feeling better. Our study shows that there is very little change in symptom burden at 1 year following transplant in general, but MF-specific symptoms showed improvement. By 1 year, 61% felt that their QoL was better than it was before transplant.

CSF Pressure, Volume, and Post-Dural Puncture Headache: A Case-Control Study and Systematic Review.

OBJECTIVES: (1) To perform a systematic literature review to evaluate associations between post-dural puncture headache (PDPH) and opening pressure (OP), closing pressure (CP), and volume of cerebrospinal fluid (V) removed. (2) To perform a case-control study to evaluate pressure-volume index (PVI) as a novel risk factor for PDPH. BACKGROUND: According to the International Classification of Headache Diagnoses, 3rd Edition (ICHD-3), the diagnosis of PDPH requires documentation of intracranial hypotension. However, this remains an unproven concept. METHODS: A systematic literature review was conducted, searching Cochrane Database of Systematic Reviews, Ovid EMBASE, OVID MEDLINE, Scopus, and Web of Science. Study inclusion required a comparison of headache incidence following a LP as a function of OP, CP, and/or V. A retrospective, case-control study with 1:1 matching was conducted utilizing ICHD-3 criteria. Patients with factors that could influence CSF pressure were excluded. RESULTS: In our case-control study, we did not identify a paired difference in either median (95% CI) elastance (0.05 [-0.09, 0.11], P = .503) or PVI (4.53 [-7.98, 19.97], P = .678). We identified 22 references, evaluating V (n = 14), OP (n = 11), and/or CP (n = 4). There was no convincing evidence for an association of PDPH with either OP or CP. A minority of studies documenting an association with V included patients with high-volume CSF removal, and/or stratified patients by the timing of the headache onset. CONCLUSIONS: The overall risk of PDPH does not appear to be influenced by OP, CP, V or PVI. PDPH may be related to V in instances of high-volume removal, and depend on the timing of outcome assessment. Future revision of criteria should consider the existence of immediate and delayed PDPH subtypes, and not presume intracranial hypotension as a mandatory feature.