Patient Outcome Variables Research Articles

Genomic and prognostic heterogeneity among RAS/BRAFV600E /TP53 co-mutated resectable colorectal liver metastases.

Hepatic resection is potentially curative for patients with colorectal liver metastases, but the treatment benefit varies. KRAS/NRAS (RAS)/TP53 co-mutations are associated with a poor prognosis after resection, but there is large variation in patient outcome within the mutation groups, and genetic testing is currently not used to evaluate benefit from surgery. We have investigated the potential for improved prognostic stratification by combined biomarker analysis with DNA copy number aberrations (CNAs), and taking tumor heterogeneity into account. We determined the mutation status of RAS, BRAFV600 , and TP53 in 441 liver lesions from 171 patients treated by partial hepatectomy for metastatic colorectal cancer. CNAs were profiled in 232 tumors from 67 of the patients. Mutations and high-level amplifications of cancer-critical genes, the latter including ERBB2 and EGFR, were predominantly homogeneous within patients. RAS/BRAFV600E and TP53 co-mutations were associated with a poor patient outcome (hazard ratio, HR, 3.9, 95% confidence interval, CI, 1.3-11.1, P=0.012) in multivariable analyses with clinicopathological variables. The genome-wide CNA burden and intrapatient intermetastatic CNA heterogeneity varied within the mutation groups, and the CNA burden had prognostic associations in univariable analysis. Combined prognostic analyses of RAS/BRAFV600E /TP53 mutations and CNAs, either as a high CNA burden or high intermetastatic CNA heterogeneity, identified patients with a particularly poor outcome (co-mutation/high CNA burden: HR 2.7, 95% CI 1.2-5.9, P=0.013; co-mutation/high CNA heterogeneity: HR 2.5, 95% CI 1.1-5.6, P=0.022). In conclusion, DNA copy number profiling identified genomic and prognostic heterogeneity among patients with resectable colorectal liver metastases with co-mutated RAS/BRAFV600E /TP53.

Rapid standardized operating rooms (RAPSTOR) in thyroid and parathyroid surgery

ObjectiveTo evaluate the impact of a high efficiency rapid standardized OR (RAPSTOR) for hemithyroid/parathyroid surgery using standardized equipment sets (SES) and consecutive case scheduling (CCS) on turnover times (TOT), average case volumes, patient outcomes, hospital costs and OR efficiency/stress.MethodsPatients requiring hemithyroidectomy (primary or completion) or unilateral parathyroidectomy in a single surgeon’s practice were scheduled consecutively with SES. Retrospective control groups were classified as sequential (CS) or non-sequential (CNS). A survey regarding OR efficiency/stress was administered. Phenomenography and descriptive statistics were conducted for time points, cost and patient outcome variables. Hospital cost minimization analysis was performed.ResultsThe mean TOT of RAPSTOR procedures (16 min; n = 27) was not significantly different than CS (14 min, n = 14) or CNS (17 min, n = 6). Mean case number per hour was significantly increased in RAPSTOR (1.2) compared to both CS (0.9; p < 0.05) and CNS (0.7; p < 0.05). Average operative time was significantly reduced in RAPSTOR (32 min; n = 28) compared to CNS (48 min; p < 0.05) but not CS (33 min; p = 0.06). Time to discharge was reduced in RAPSTOR (595 min) compared to CNS (1210 min, p < 0.05). There was no difference in complication rate between all groups (p = 0.27). Survey responses suggested improved efficiency, teamwork and workflow. Furthermore, there is associated decrease in direct operative costs for RAPSTOR vs. CS.ConclusionA high efficiency standardized OR for hemithyroid and parathyroid surgery using SES and CCS is associated with improved efficiency and, in this study, led to increased capacity at reduced cost without compromising patient safety.Level of evidenceLevel 2.Graphical abstract

Challenges in communication, prognostication and dialysis decision-making in the COVID-19 pandemic: implications for interdisciplinary care during crisis settings.

Using case vignettes, we highlight challenges in communication, prognostication, and medical decision-making that have been exacerbated by the coronavirus disease-19 (COVID-19) pandemic for patients with kidney disease. We include best practice recommendations to mitigate these issues and conclude with implications for interdisciplinary models of care in crisis settings. Certain biomarkers, demographics, and medical comorbidities predict an increased risk for mortality among patients with COVID-19 and kidney disease, but concerns related to physical exposure and conservation of personal protective equipment have exacerbated existing barriers to empathic communication and value clarification for these patients. Variability in patient characteristics and outcomes has made prognostication nuanced and challenging. The pandemic has also highlighted the complexities of dialysis decision-making for older adults at risk for poor outcomes related to COVID-19. The COVID-19 pandemic underscores the need for nephrologists to be competent in serious illness communication skills that include virtual and remote modalities, to be aware of prognostic tools, and to be willing to engage with interdisciplinary teams of palliative care subspecialists, intensivists, and ethicists to facilitate goal-concordant care during crisis settings.

A recurring NFS1 pathogenic variant causes a mitochondrial disorder with variable intra-familial patient outcomes

Iron‑sulfur clusters (FeSCs) are vital components of a variety of essential proteins, most prominently within mitochondrial respiratory chain complexes I-III; FeS assembly and distribution is performed via multi-step pathways. Variants affecting several proteins in these pathways have been described in genetic disorders, including severe mitochondrial disease. Here we describe a Christian Arab kindred with two infants that died due to mitochondrial disorder involving FeS containing respiratory chain complexes and a third sibling who survived the initial crisis. A homozygous missense variant in NFS1: c.215G>A; p.Arg72Gln was detected by whole exome sequencing. The NFS1 gene encodes a cysteine desulfurase, which, in complex with ISD11 and ACP, initiates the first step of FeS formation. Arginine at position 72 plays a role in NFS1-ISD11 complex formation; therefore, its substitution with glutamine is expected to affect complex stability and function. Interestingly, this is the only pathogenic variant ever reported in the NFS1 gene, previously described once in an Old Order Mennonite family presenting a similar phenotype with intra-familial variability in patient outcomes. Analysis of datasets from both populations did not show a common haplotype, suggesting this variant is a recurrent de novo variant.Our report of the second case of NFS1-related mitochondrial disease corroborates the pathogenicity of this recurring variant and implicates it as a hot-spot variant. While the genetic resolution allows for prenatal diagnosis for the family, it also raises critical clinical questions regarding follow-up and possible treatment options of severely affected and healthy homozygous individuals with mitochondrial co-factor therapy or cysteine supplementation.

Hospital and surgeon variation in 30-day complication rates after ventral hernia repair

BackgroundVentral hernia repair is an extremely common operation, however the variability in patient outcomes between individual hospitals and surgeons is unclear. We analyzed variability in 30-day complication rates and identified specific complications that contributed to this variability. MethodsRetrospective, cross-sectional analysis of 30-day complication rates following ventral hernia repair across 73 hospital and 978 surgeons between January 1, 2014 and December 31, 2018. ResultsData were collected on 19,007 patients who underwent VIHR at 73 hospitals across 978 surgeons. Adjusted complication rate among hospitals was 6.2% (range 4.3%–12.8%) and among surgeons was 6.2% (range 3.5%–26.8%). Variation between lowest and highest quartile surgeons was greatest for acute kidney injury (0.12% vs. 1.71%, P < 0.001), superficial surgical site infection (0.33% vs. 3.62%, P < 0.001), sepsis (0.27% vs. 2.47%, P < 0.001), and catheter-associated urinary tract infection (0.02% vs. 0.30%, P < 0.001). ConclusionAfter adjusting for a number of patient-specific clinical variables, there is significant variation in 30-day complication rates after ventral hernia repair. This represents a significant opportunity to improve patient outcomes.

Site-Level Variability in 30-Day Patient Outcomes After Transcatheter Mitral Valve Repair in the United States.

Clinical trials have demonstrated health status benefit of transcatheter mitral valve repair (TMVr) with MitraClip in patients with mitral valve regurgitation. Real-world site-level variability in health status outcomes for TMVr, and factors associated with this variability, are unknown. All patients undergoing TMVr procedure with MitraClip between November 2013 and March 2019 in the Transcatheter Valve Therapy Registry were included. Health status was measured at baseline and 30 days with the Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary (OS) score. Site-level variability in 30-day change in KCCQ-OS was examined by calculating the median odds ratio from a hierarchical logistic regression model, with ≥20-point improvement as the dependent variable. To define the extent to which patient characteristics, procedural characteristics (residual mitral valve regurgitation, periprocedural bleeding), site volume, and patients' baseline health status accounted for variability in outcomes, the proportion of variability (R2) explained by sequentially adding these variables to the model was quantified. Across 339 sites, 12 415 patients (mean age 79.0±9.5 years, 46.1%. females, 89.5% White) completed baseline and 30-day health status assessments. Mean KCCQ-OS score was 43.0±24.4 at baseline and 67.0±24.9 at 30-day follow-up. Across sites, the proportion of patients achieving a ≥20-point improvement in KCCQ-OS ranged from 12.5% to 100% and the adjusted median odds ratio was 1.58 (95% CI, 1.46-1.69). The greatest contribution to the variability in health status outcomes was from patients' baseline KCCQ-OS score (R2=25%) with <1% of the variability explained by patient and procedural characteristics, and annual site volume. There is moderate variation across sites in their patients' achievement of health status benefits from TMVr, with patient's baseline health status accounting for the largest proportion of this variation. This underscores the importance of patient selection in supporting more consistent health status benefit from TMVr.

Abstract PR-009: Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms

Abstract Background Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous neoplasms with variable patient outcomes. Our study aims to uncover the molecular factors that underlie the clinical and biological heterogeneity among PNENs for a better understanding and potential classification of this disease. Methods Formalin-fixed paraffin-embedded primary tumour specimens from 92 patients with PNEN were procured for the study and split into two cohorts for discovery and validation purposes. Next-generation sequencing profiled the exome and transcriptome, and quantitative mass-spectrometry profiled the global proteome of specimens. Non-negative matrix factorization was used to identify subgroups, followed by differential analysis to identify subgroup-specific features. To corroborate subgroup-specific RNA- and protein- level distinctions, activities of key cellular regulators were inferred from target gene expression or co-expression signatures. Results Unsupervised clustering analysis of transcriptome data identified four robust molecular subgroups that were substantiated by proteome analysis (p=0.0005) within the discovery cohort and validated with the validation cohort and an external cohort of PNENs from a previous microarray-based gene expression study. A proliferative subgroup was enriched with neuroendocrine carcinomas and specimens with &amp;gt;20% Ki67, concomitant with reduced survival probability (p=0.0024; logrank test) and higher mRNA expression and protein abundance of cell cycle-related genes. Increased mRNA expression of ARX or PDX1 (adjusted p&amp;lt;0.05) was found in two of the subgroups similar to a previous report. The ARX-high subgroup was characterized by enrichment of oxidative phosphorylation genes and increased relative abundance of mitochondrial proteins, while oncogenic Ras mutations were found in the PDX1-high subgroup. A fourth subgroup exhibited enrichment of stromal/mesenchymal molecular features and Hippo signaling pathway. Inferred activities of key cellular regulators further supported observed alterations within subgroups. Conclusions We identified four robust molecular subgroups among PNENs with clinicopathological associations and biological distinctions that may provide potential new directions for patient stratification and treatment strategies to facilitate treatment decisions. Citation Format: Kevin C. Yang, Steve Kalloger, John Aird, Michael Lee, Christopher Rushton, Sandra E. Spencer Miko, Karen L. Mungall, Andrew J. Mungall, Shane Colborne, Ryan D. Morin, Jonathan M. Loree, Marco A. Marra, Daniel J. Renouf, Gregg B. Morin, David F. Schaeffer, Sharon M. Gorski. Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PR-009.

Factors Associated With Home Visits in a 5-Year Study of Acute Respiratory Distress Syndrome Survivors.

Participant retention is vital for longitudinal studies. Home visits may increase retention, but little is known about the subset of patients they benefit. To evaluate patient-related variables associated with home visits. In a 5-year, longitudinal, multisite, prospective study of 195 survivors of acute respiratory distress syndrome, in-person assessments were conducted at a research clinic. Home visits were offered to participants who could not attend the clinic. Associations between having a home visit, prior follow-up visit status, and baseline and in-hospital patient variables were evaluated with multivariable, random-intercept logistic regression models. The association between home visits and patients' posthospital clinical status was evaluated with a subsequent regression model adjusted for these variables. Participants had a median age of 49 years and were 56% male and 58% White. The following had independent associations with home visits (adjusted odds ratio [95% CI]): age (per year: 1.03 [1.00-1.05]) and immediately preceding visit incomplete (2.46 [1.44-4.19]) or at home (8.24 [4.57-14.86]). After adjustment for prior-visit status and baseline and hospitalization variables, these posthospital patient outcome variables were associated with a subsequent home visit: instrumental activities of daily living (≥ 2 vs < 2 dependencies: 2.32 [1.29-4.17]), EQ-5D utility score (per 0.1-point decrease: 1.15 [1.02-1.30]), and 6-minute walk test (per 10-percentage-point decrease in percent-predicted distance: 1.50 [1.26-1.79]). Home visits were important for retaining older and more physically impaired study participants, helping reduce selection bias caused by excluding them.

Surgical Outcomes After Single-Level Endoscopic Transforaminal Lumbar Interbody Fusion: A Systematic Review and Meta-Analysis.

Background and objectiveNovel surgical advancements have introduced endoscopic operative techniques for low back surgery, including transforaminal lumbar interbody fusion (TLIF), which theoretically allows for improved decompression with minimal invasiveness. In addition, endoscopically performed TLIF has allowed for the use of local anesthesia as an alternative method to general anesthesia for patients. We aimed to evaluate the clinical outcomes in patients undergoing endoscopic TLIF and also compare the outcomes in patients undergoing general versus local anesthesia.MethodsThe databases of PubMed, Medline, Embase, and the Cochrane Library were queried for all studies involving patients undergoing endoscopic TLIF. After the extraction of the data and assessment of study quality via the Newcastle-Ottawa Scale, statistical analysis was performed with the R software (The R Foundation, Vienna, Austria) metafor package. The random-effects model was used as the data was largely heterogeneous (I2 >50%).ResultsIn total, 15 studies involving a total of 441 patients were selected for the final quantitative meta-analysis. The overall mean difference between the postoperative visual analog scale (VAS) leg scores and preoperative VAS scores was 3.45 (95% CI: 4.93-1.97, p: <0.01). Postoperative VAS low back scores revealed a mean difference of 3.36 (95% CI: 5.09-1.63, p: <0.01). The overall mean difference of ODI scores was 4.58 (95% CI: 6.76-2.40, p: <0.01). Mean blood loss was 136.32 mL and the mean operative time was 149.15 minutes. The mean length of stay postoperatively was lower in the local anesthesia group compared to the general anesthesia group (1.40 vs 5.99 days respectively). There were no outcome variables of patients undergoing general anesthesia versus local anesthesia that showed statistically significant differences in this analysis due to the small amount of data published on patients undergoing endoscopic TLIF with local anesthesia. In addition, the failure of studies in reporting standard deviations as data parameters further limited the quantitative analysis.ConclusionEndoscopic TLIF appears to be a viable option for patients undergoing lumbar interbody fusion. Initial data reveal that endoscopic TLIF with local anesthesia may offer patients outcomes similar to those in patients undergoing endoscopic TLIF with general anesthesia, with lower operative times and length of stay.

Preoperative opioid, sedative, and antidepressant use is associated with increased postoperative hospital costs in colorectal surgery.

BackgroundOpioid (OPD), sedative (SDT), and antidepressant (ADM) prescribing has increased dramatically over the last 20 years. This study evaluated preoperative OPD, SDT, and ADM use on hospital costs in patients undergoing colorectal resection at a single institution.MethodsThis study was a retrospective record review. The local ACS-NSQIP database was queried for adult patients (age ≥ 18 years) undergoing open/laparoscopic, partial/total colectomy, or proctectomy from January 1, 2013 to December 31, 2016. Individual patient medical records were reviewed to determine preoperative OPD, SDT, and AD use. Hospital cost data from index admission were captured by the hospital cost accounting system and matched to NSQIP query-identified cases. All ACS-NSQIP categorical patient characteristic, operative risk, and outcome variables were compared in medication groups using chi-square tests or Fisher’s exact tests, and continuous variables were compared using Mann–Whitney U tests.ResultsA total of 1185 colorectal procedures were performed by 30 different surgeons. Of these, 27.6% patients took OPD, 18.5% SDT, and 27.8% ADM preoperatively. Patients taking OPD, SDT, and ADM were found to have increased mean total hospital costs (MTHC) compared to non-users (30.8 vs 23.6 for OPD, 31.6 vs 24.4 for SDT, and 30.7 vs 23.8 for ADM). OPD and SDT use were identified as independent risk factors for increased MTHC on multivariable analysis.ConclusionPreoperative OPD and SDT use can be used to predict increased MTHC in patients undergoing colorectal resections.

Impact of "Time-From-Biopsy-to-Prostatectomy" on Adverse Oncological Results in Patients With Intermediate and High-Risk Prostate Cancer.

Objective: Many patients with localized prostate cancer (PCa) do not immediately undergo radical prostatectomy (RP) after biopsy confirmation. The aim of this study was to investigate the influence of “time-from-biopsy-to- prostatectomy” on adverse pathological outcomes.Materials and Methods: Between January 2014 and December 2019, 437 patients with intermediate- and high risk PCa who underwent RP were retrospectively identified within our prospective institutional database. For the aim of our study, we focused on patients with intermediate- (n = 285) and high-risk (n = 151) PCa using D'Amico risk stratification. Endpoints were adverse pathological outcomes and proportion of nerve-sparing procedures after RP stratified by “time-from-biopsy-to-prostatectomy”: ≤3 months vs. >3 and < 6 months. Medians and interquartile ranges (IQR) were reported for continuously coded variables. The chi-square test examined the statistical significance of the differences in proportions while the Kruskal-Wallis test was used to examine differences in medians. Multivariable (ordered) logistic regressions, analyzing the impact of time between diagnosis and prostatectomy, were separately run for all relevant outcome variables (ISUP specimen, margin status, pathological stage, pathological nodal status, LVI, perineural invasion, nerve-sparing).Results: We observed no difference between patients undergoing RP ≤3 months vs. >3 and <6 months after diagnosis for the following oncological endpoints: pT-stage, ISUP grading, probability of a positive surgical margin, probability of lymph node invasion (LNI), lymphovascular invasion (LVI), and perineural invasion (pn) in patients with intermediate- and high-risk PCa. Likewise, the rates of nerve sparing procedures were 84.3 vs. 87.4% (p = 0.778) and 61.0% vs. 78.8% (p = 0.211), for intermediate- and high-risk PCa patients undergoing surgery after ≤3 months vs. >3 and <6 months, respectively. In multivariable adjusted analyses, a time to surgery >3 months did not significantly worsen any of the outcome variables in patients with intermediate- or high-risk PCa (all p > 0.05).Conclusion: A “time-from-biopsy-to-prostatectomy” of >3 and <6 months is neither associated with adverse pathological outcomes nor poorer chances of nerve sparing RP in intermediate- and high-risk PCa patients.

How Context Influences Hospital Readmissions from Skilled Nursing Facilities: A Rapid Ethnographic Study

IntroductionImproving hospital discharge processes and reducing adverse outcomes after hospital discharge to skilled nursing facilities (SNFs) are gaining national recognition. However, little is known about how the social-contextual factors of hospitals and their affiliated SNFs may influence the discharge process and drive variations in patient outcomes. We sought to categorize contextual drivers that vary between high- and low-performing hospitals in older adult transition from hospitals to SNFs. DesignTo identify contextual drivers, we used a rapid ethnographic approach with interviews and direct observations of hospital and SNF clinicians involved in discharging patients. We conducted thematic analysis to categorize contextual factors and compare differences in high- and low-performing sites. Setting and ParticipantsWe stratified hospitals on 30-day hospital readmission rates from SNFs and used convenience sampling to identify high- and low-performing sites and associated SNFs. The final sample included 4 hospitals (n = 2 high performing, n = 2 low performing) and affiliated SNFs (n = 5) with 148 hours of observations. MeasuresCentral themes related to how contextual factors influence variations in high- and low-performing hospitals. ResultsWe identified 3 main contextual factors that differed across high- and low-performing hospitals and SNFs: team dynamics, patient characteristics, and organizational context. First, we observed high-quality communication, situational awareness, and shared mental models among team members in high-performing sites. Second, the types of patients cared for at high-performing hospitals had better insurance coverage that made it feasible for clinicians to place patients based on their needs instead of financial abilities. Third, at high-performing hospitals a more engaged staff in the transition process and building rapport with SNFs characterized smooth transitions from hospitals to SNFs. Conclusions and ImplicationsContextual factors distinguish high- and low-performing hospitals in transitions to SNF and can be used to develop interventions to reduce adverse outcomes in transitions.

Effect of inspiratory muscle training in hypercapnic chronic obstructive pulmonary disease patients during acute care: a randomised clinical trial

Weakness of respiratory muscles along with respiratory failure is a common finding in chronic obstructive pulmonary disease (COPD) patients which leads to dyspnoea and hence decreased functional capacity. Despite a sound theoretical rationale regarding the potential role of inspiratory muscles, the role of inspiratory muscle training (IMT) along with the conventional non-invasive ventilation (NIV) on important clinical outcomes has not been investigated in these patients during acute care. 34 hypercapnic stable COPD patients were randomly allocated to one of the interventions that lasted for 10 days: IMT with NIV (n=17), and NIV alone (n=17). IMT was administered 2 times in a day (15 min each time) by threshold loading at an intensity starting from 30% and progressed to 60% of their maximal inspiratory effort (PImax). NIV was given at an optimal pressure titrated for each patient for at least &gt;8 h per day. Outcome measures (respiratory muscle strength, respiratory failure, dyspnoea, and functional capacity) were assessed before and after 10 days of intervention. Clinical characteristics and outcome variables of patients were similar between the groups at baseline. Addition of IMT led to a significantly greater increase in respiratory muscle strength (P=0.01), reduction in dyspnea (modified medical research council dyspnea scale, P=0.001); improved outcomes of respiratory failure (PaCO2, P=0.03; PaO2, P=0.002) and improved functional capacity (6 min walk distance, P=0.001) as compared to NIV alone. A short duration IMT program in addition to NIV was found to be effective in improving respiratory muscle strength, perception of dyspnoea, functional capacity and respiratory failure in hypercapnic COPD patients.

Association Between Surgeon Technical Skills and Patient Outcomes

Postoperative complications remain common after surgery, but little is known about the extent of variation in operative technical skill and whether variation is associated with patient outcomes. To examine the (1) variation in technical skill scores of practicing surgeons, (2) association between technical skills and patient outcomes, and (3) amount of variation in patient outcomes explained by a surgeon's technical skill. In this quality improvement study, 17 practicing surgeons submitted a video of a laparoscopic right hemicolectomy that was then rated by at least 10 blinded peer surgeons and 2 expert raters. The association between surgeon technical skill scores and risk-adjusted outcomes was examined using data from the American College of Surgeons National Surgical Quality Improvement Program. The association between technical skill scores and outcomes was examined for colorectal procedures and noncolorectal procedures (ie, assessed on whether technical skills demonstrated during colectomy were associated with patient outcomes across other cases). In addition, the proportion of patient outcomes explained by technical skill scores was examined using robust regression techniques. The study was conducted from September 23, 2016, to February 10, 2018; data analysis was performed from November 2018 to January 2019. Colorectal and noncolorectal procedures. Any complication, mortality, unplanned hospital readmission, unplanned reoperation related to principal procedure, surgical site infection, and death or serious morbidity. Of the 17 surgeons included in the study, 13 were men (76%). The participants had a range from 1 to 28 years in surgical practice (median, 11 years). Based on 10 or more reviewers per video and with a maximum quality score of 5, overall technical skill scores ranged from 2.8 to 4.6. From 2014 to 2016, study participants performed a total of 3063 procedures (1120 colectomies). Higher technical skill scores were significantly associated with lower rates of any complication (15.5% vs 20.6%, P = .03; Spearman rank-order correlation coefficient r = -0.54, P = .03), unplanned reoperation (4.7% vs 7.2%, P = .02; r = -0.60, P = .01), and a composite measure of death or serious morbidity (15.9% vs 21.4%, P = .02; r = -0.60, P = .01) following colectomy. Similar associations were found between colectomy technical skill scores and patient outcomes for all types of procedures performed by a surgeon. Overall, technical skill scores appeared to account for 25.8% of the variation in postcolectomy complication rates and 27.5% of the variation when including noncolectomy complication rates. The findings of this study suggest that there is wide variation in technical skill among practicing surgeons, accounting for more than 25% of the variation in patient outcomes. Higher colectomy technical skill scores appear to be associated with lower complication rates for colectomy and for all other procedures performed by a surgeon. Efforts to improve surgeon technical skills may result in better patient outcomes.

Maximal strength training in patients with Parkinson's disease: impact on efferent neural drive, force-generating capacity, and functional performance.

Parkinson's disease (PD) is characterized by progressive neurological deterioration, typically accompanied by reductions in skeletal muscle force-generating capacity (FGC) and functional performance. Physical activity has the potential to counteract this debilitating outcome, however, it is elusive if high-intensity strength training included in conventional treatment may improve results. Therefore, we randomly assigned 22 PD patients (74 ± 9 yr) to conventional rehabilitation with or without maximal strength training (MST) performed as leg press and chest press at ~90% of one repetition maximum (1RM), five times per week for 4 wk. FGC, physical performance, and efferent neural drive assessed as evoked potentials (V-wave normalized to M-wave in m. soleus) were measured following training. Results revealed that only MST improved 1RM leg press (101 ± 23 to 118 ± 18 kg) and chest press (36 ± 15 to 41 ± 15 kg), plantar flexion maximal voluntary contraction (235 ± 125 to 293 ± 158 N·m), and rate of force development (373 ± 345 to 495 ± 446 N·m·s-1; all P < 0.05; different from controls P < 0.05). FGC improvements were accompanied by an increased efferent neural drive to maximally contracting musculature (V-to-M ratio: 0.17 ± 0.12 to 0.24 ± 0.15; P < 0.05; different from controls P < 0.05), improved physical performance (stair climbing: 21.0 ± 9.2 to 14.4 ± 5.2 s; timed up and go: 7.8 ± 3.3 to 6.2 ± 2.5 s; both P < 0.05), and self-perceived improvement in health (3.1 ± 0.5 to 2.6 ± 0.9) and social activities functioning (2.2 ± 1.0 to 1.5 ± 1.1; both P < 0.05). No changes were observed in the control group. In conclusion, this study shows that MST improves FGC, neuromuscular function, and functional performance and advocates that high-intensity strength training should be implemented as an adjunct therapy in the treatment of PD patients.NEW & NOTEWORTHY This randomized, controlled trial documents that supervised high-intensity strength training improves efferent neural drive, maximal muscle strength, rate of force development, and functional performance in patients with Parkinson's disease (PD). In contrast, no differences were observed in these outcome variables in patients receiving conventional treatment consisting of recreational physical activity with low-to-medium intensity. Consequently, this study advocates that high-intensity strength training should be implemented in the clinical treatment of PD patients.

Characteristics of pediatric patients with traumatic epidural hematomas who can be safely observed: a clinical validation study

The study aimed to validate admission clinical and radiographic features of pediatric patients with traumatic epidural hematoma (EDH) that lead to safe observation. A Level I trauma center radiology and electronic medical record databases were retrospectively queried for pediatric patients with EDH on CT scan between 1/1/2016 and 10/1/2016. Patient imaging, treatment and outcome variables were abstracted. Characteristics of the cohort were compared to an external cohort used to develop prediction rules for surgical intervention. External validity of the prediction rules was assessed. 195 eligible subjects were included in the study, 37 of which failed observation and required surgery while 158 underwent successful observation. The surgical cohort had significantly thicker (p < .001) and higher volume (p < .001) EDH, increased midline shift (p < .001) and higher likelihood of mass effect (p < .001). There was significantly higher residual neurologic deficit rate (54% vs 23%, p < .001) and hospital mortality (5% vs 0%, p = .035) amongst the surgical group. There were significant differences in patient demographic, clinical and imaging characteristics between the internal and external cohorts. The predictive rules externally developed yielded positive predictive value of 97.7% (95% CI = 93.3-99.5%), negative predictive value of 24.5% (95% CI = 16.2-34.4%), specificity of 88.5% (95% CI = 69.9-97.6%), and sensitivity of 63.8% (95% CI = 56.6-70.5%) for successful observation. The current study validates previously developed prediction rules for safe observation of pediatric EDH in a cohort with distinct characteristics from the external cohort. Specifically, patients with no mass effect, EDH volume <15 ml and no neurological deficits are less likely to fail observation. The current study validates prediction rules for safe observation of pediatric EDH in a distinct pediatric cohort that provides further support to conservative management in these circumstances.

Low serum lymphocyte level is associated with poor exercise capacity and quality of life in chronic obstructive pulmonary disease

The purpose of this study was to evaluate the association of serum lymphocyte level with several clinical parameters in COPD. The study population included 451 COPD patients from the Korean Obstructive Lung Disease cohort study. Serum lymphocyte level was measured every year along with various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life using COPD assessment test (CAT) and St. George's Respiratory Questionnaire (SGRQ) scores, exacerbations, and survival. Serum lymphocyte level less than 20% was considered as a low lymphocyte level. Normal lymphocyte and low lymphocyte groups comprised of 409 (90.7%) and 42 (9.3%) patients, respectively. Clustered analysis showed that patients in low lymphocyte group had a lower post-bronchodilator forced expiratory volume in 1 s % predicted (estimated mean = − 5.70%; P = 0.001), a lower forced vital capacity % predicted (estimated mean = − 5.63%; P = 0.005), a shorter 6 MW distance (estimated mean = − 41.31 m; P < 0.001), a higher CAT score (estimated mean = 2.62; P = 0.013), and a higher SGRQ score (estimated mean = 10.10; P < 0.001). Serum lymphocyte level was not associated with frequent acute exacerbations nor mortality. Low serum lymphocyte group showed poorer pulmonary function, lower 6 MW distance, and worse quality of life. Serum lymphocyte levels could be a simple and widely available predictive marker for variable clinical outcomes in COPD patients.

A Retrospective Cohort Study Evaluating Surgical Aptitude Over Time in a New Male-To-Female Penoscrotal Vaginoplasty Program

BackgroundGiven the burgeoning demand for gender affirmation surgery, there are few studies examining both surgical process variables and patient outcome variables. Knowing the learning curve for surgical teams who are beginning to perform this procedure will be important for patient safety and presurgical patient counseling as more institutions open transgender surgical programs. AimThe purpose of this study was to determine the demographics of patients pursuing penoscrotal vaginoplasty, to determine their postoperative course, and to determine a learning curve for the surgical team performing penoscrotal vaginoplasty. MethodsWe retrospectively reviewed charts of all 43 patients who underwent penoscrotal vaginoplasty from the commencement of a new male-to-female penoscrotal vaginoplasty program in March 2018 through July 2019. OutcomesPrimary outcomes included mean hemoglobin decrease from surgery and operative time. Mean time to neoclitoral sensation, length of hospital admission, complication rates, reoperation rates, length of narcotic use after surgery, and demographics were also evaluated. Associations between surgical team experience and outcomes were assessed with Spearman's rho and Cox regression, and curve-fitting procedures were applied to determine the relationship. ResultsThe mean operative time from initial incision to procedure finish was 225 minutes, and the mean decrease in hemoglobin was 3.3 g/dL. The mean time to neoclitoral sensation was 0.72 months. The time until neoclitoral sensation decreased as the surgical cases performed increased (Spearman's rho, −0.577 [P < .001]), with a power function best describing the learning curve. Operative time did not change with case number (Spearman's rho, 0.062 [P = .698]) but overall time in the operating room did (Spearman's rho, 0.631 [P < .001]). Mean length of hospital admission was 2.9 days. There were no intraoperative complications. 18 patients (42%) experienced a postoperative complication. 8 of 43 patients underwent reoperation (20%). Narcotics were used a mean of 9.5 days after surgery. Clinical ImplicationsA learning curve can be demonstrated in penoscrotal vaginoplasty for time to neoclitoral sensation and overall time in the operating room, plateauing between 30 and 40 cases. Strengths and LimitationsStrengths include assessing a learning curve for time to neoclitoral sensation, length of hospital stay, and length of postoperative narcotic use after penoscrotal vaginoplasty, which, to our knowledge, has not been reported elsewhere. Limitations include our overall low number of patients. ConclusionDespite a low number of cases, length of hospital stay was short and the postoperative complication rate was similar to that of long-standing penoscrotal vaginoplasty programs.Whynott RM, Summers K, Mickelsen R, et al. A Retrospective Cohort Study Evaluating Surgical Aptitude Over Time in a New Male-To-Female Penoscrotal Vaginoplasty Program. J Sex Med 2020;17:1787–1794.

KRAS Status is Associated with Metabolic Parameters in Metastatic Colorectal Cancer According to Primary Tumour Location

Colorectal cancer (CRC) is characterized by complex interplay between macroenvironmental factors and tumour microenvironment, leading to variable outcomes in CRC patients. To date, there is still a need to identify macroenvironment/microenvironment factors that could define subgroup of patients that would benefit from specific anti-cancer treatment in order to improve patient selection for individualized targeted-based therapy. Aim of this study was to evaluate associations between metabolic parameters and KRAS status in metastatic CRC (mCRC) according to a new tumour site classification. Retrospective data were extracted from a total of 201 patients diagnosed with mCRC between 2012 and 2017 extracted from an established CRC database at our tertiary institute. Clinical-pathological data, including age, gender, BMI, hypertension, diabetes, pre-CRC diagnosis serum lipid levels and KRAS status were recorded. Categorical characteristics were compared using chi-squared test. Continuous characteristics were compared using Mann-Whitney U test. Log rank test was used to compare hazards for survival. In all comparisons, a two-sided P value <0.05 was considered statistically significant. Out of 201 patients, 170 patients with complete serum lipid profile were included in the analysis. In recto-sigmoid cancers there was a statistically significant association between high cholesterol:high-density lipoprotein (chol:HDL) ratio and KRAS mutation (OR 2.69, 95% CI 1.1–6.4, p = 0,02). In non recto-sigmoid cancers, high cholesterol was associated with KRAS WT (OR 0.39, CI 0.15–0.97, p = 0.04). In 22 patients with KRAS mutated recto-sigmoid cancer stage IV at diagnosis normal chol:HDL ratio was associated with a trend to better survival (p = 0.06). High chol:HDL ratio was significantly associated with KRAS mutated metastatic recto-sigmoid cancers. A subgroup of mCRC patients with KRAS mutated recto-sigmoid cancer may benefit from optimal lipid lowering treatment.

Epidemiological Determinants of COVID-19-Related Patient Outcomes in Different Countries and Plan of Action: A Retrospective Analysis

Current development around the pandemic of novel coronavirus disease 2019 (COVID-19) presents a significant healthcare resource burden threatening to overwhelm the available nationwide healthcare infrastructure. It is essential to consider, especially for resource-limited nations, strategizing the coordinated response to handle this crisis effectively and preparing for the upcoming emergence of calamity caused by this yet-to-know disease entity.Relevant epidemiological data were retrieved from currently available online reports related to COVID-19 patients. The correlation coefficient was calculated by plotting dependant variables - the number of COVID-19 cases and the number of deaths due to COVID 19 on the Y-axis and independent variables - critical-care beds per capita, the median age of the population of the country, the number of COVID-19 tests per million population, population density (persons per square km), urban population percentage, and gross domestic product (GDP) expense on health care - on the X-axis.After analyzing the data, both the fatality rate and the total number of COVID-19 cases were found to have an inverse association with the population density with the variable - the number of cases of COVID-19 - achieving a statistical significance (p-value 0.01). The negative correlation between critical care beds and the fatality rate is well-justified, as intensive care unit (ICU) beds and ventilators are the critical elements in the management of complicated cases. There was also a significant positive correlation between GDP expenses on healthcare by a country and the number of COVID-19 cases being registered (p-value 0.008), although that did not affect mortality (p-value 0.851).This analysis discusses the overview of various epidemiological determinants possibly contributing to the variation in patient outcomes across regions and helps improve our understanding to develop a plan of action and effective control measures in the future.