Series on the Lancet Oncology Commission on Global Cancer Surgery: Introduction-Intent and Content.

BACKGROUND: Surgery plays a key role in the multi-disciplinary cancer care pathway. Nearly 80% of patients with solid tumors will require surgical intervention during the course of their disease. Unfortunately, the vast majority of these patients do not have access to safe, timely, high-quality, and affordable cancer surgical care. The first Lancet Oncology Commission on Global Cancer Surgery shone a light on this grave situation and outlined some strategies to address them. The second Lancet Oncology Commission on Global Cancer Surgery (TLO- II) was conceived to continue the work of its predecessor by developing a roadmap of practical solutions to propel improvements in cancer surgical care globally. METHODS: The Commission was developed by involving approximately 50 cancer care leaders and experts from different parts of the world to ensure diversity of input and global applicability. RESULTS: The Commission identified nine solutional domains that are considered essential to deliver safe, timely, high-quality, and affordable cancer surgical care. These nine domains were further refined to develop solutions specific to each of the six World Health Organization regions. Based on the above solutions, we developed eight action items that are intended to propel improvements in cancer surgical care on the global stage. CONCLUSIONS: The second Lancet Oncology Commission on Global Cancer Surgery builds on the first Commission by developing a pragmatic roadmap of practical solutions that we hope will ensure access to safe, timely, high-quality, and affordable cancer surgical care for everyone regardless of their socioeconomic status or geographic location.

Nurse-Initiated Protocol to Improve Timely Antibiotic Administration in Pediatric Open Fractures.

BACKGROUND: Early administration of antibiotics in the presence of open fractures is critical in reducing infections and later complications. Current guidelines recommend administering antibiotics within 60 min of patient arrival to the emergency department, yet trauma centers often struggle to meet this metric. OBJECTIVES: This study aims to evaluate the impact of a nurse-initiated evidence-based treatment protocol on the timeliness of antibiotic administration in pediatric patients with open fractures. METHODS: A retrospective pre-post study of patients who met the National Trauma Data Standard registry inclusion criteria for open fractures of long bones, amputations, or lawn mower injuries was performed at a Midwestern United States Level II pediatric trauma center. The time of patient arrival and time of antibiotic administration from preimplementation (2015-2020) to postimplementation (2021-2022) of the protocol were compared. Patients transferred in who received antibiotics at an outside facility were excluded. RESULTS: A total of N = 73 participants met the study inclusion criteria, of which n = 41 were in the preimplementation group and n = 32 were in the postimplementation group. Patients receiving antibiotics within 60 min of arrival increased from n = 24/41 (58.5%) preimplementation to n = 26/32 (84.4%) postimplementation (p< .05). CONCLUSIONS: Our study demonstrates that initiating evidence-based treatment orders from triage helped decrease the time from arrival to time of antibiotic administration in patients with open fractures. We sustained improvement for 24 months after the implementation of our intervention.

A Prospective Multimodal Education Intervention for Providers Does Not Increase Hepatic Encephalopathy Treatment Rates.

BACKGROUND: Over 50% of hospitalizations from hepatic encephalopathy (HE) are preventable, but patients often do not receive medical treatment. AIMS: To use a multimodal education intervention (MMEI) to increase HE treatment rates and to evaluate (1) trends in HE treatment, (2) predictors of receiving treatment, and (3) the impact of treatment on hospitalization outcomes. METHODS: Prospective single-center cohort study of patients hospitalized with HE from April 1, 2020-September 30, 2022. The first 15 months were a control ("pre-MMEI"), the subsequent 15 months (MMEI) included three phases: (1) prior authorization resources, (2) electronic order set, and (3) in-person provider education. Treatment included receiving any drug (lactulose or rifaximin), or combination therapy. Treatment rates pre- vs. post-MMEI were compared using logistic regression. RESULTS: 471 patients were included. There were lower odds of receiving any drug post-MMEI (p = 0.03). There was no difference in receiving combination therapy pre- or post-MMEI (p = 0.32). Predictors of receiving any drug included alcohol-related or cryptogenic cirrhosis (p's < 0.001), and the presence of ascites (p = 0.005) and/or portal hypertension (p = 0.003). The only significant predictor of not receiving any drug treatment was having autoimmune cirrhosis (p < 0.001). Patients seen by internal medicine (p = 0.01) or who were intoxicated (p = 0.02) were less likely to receive rifaximin. Any treatment was associated with higher 30-day liver disease-specific readmission (p < 0.001). CONCLUSION: This MMEI did not increase HE treatment rates, suggesting that alternative strategies are needed to identify and address barriers to treatment.

Restless legs syndrome is prevalent in adults with cystic fibrosis and impacts sleep quality.

BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor disorder that is prevalent in chronic inflammatory conditions. RLS prevalence, risk factors, and impact on sleep in CF have not been extensively characterized to date. METHODS: An initial cohort was examined, including 75 persons with CF (PwCF) and 75 control subjects, to look at the prevalence and severity of RLS. A second validation cohort of 191 PwCF was then enrolled from two CF centers to examine risk factors for RLS. A diagnosis of RLS was made according to the International RLS Study Group (IRLSSG) criteria. Sleep quality was identified using the Pittsburgh sleep quality index (PSQI). Epworth sleepiness scale (ESS) was used to measure daytime sleepiness. We then analyzed laboratory and clinical risk factors and sleep symptoms for potential risk factors for RLS. RESULTS: In the initial cohort, 36 % of PwCF had RLS, and 9 % of these had significant RLS. In contrast, only 15 % of controls had RLS, and none had significant RLS. In the second larger validation cohort with 191 subjects, a comparable prevalence of RLS was identified. Higher hemoglobin A1c, use of SSRI/SNRI medications, worse PSQI and ESS sleep quality scores, lower lung function, and higher antibiotic usage were significantly associated with a diagnosis of RLS. By multivariate multinominal logistic regression analysis, higher HbA1c and worse PSQI global sleep quality scores were independent predictors of significant RLS. CONCLUSIONS: RLS is highly prevalent in CF. Higher HbA1c and poor sleep quality, signified by higher PSQI, were each independent predictors of RLS.

Assessing the Safety and Efficacy of Tranexamic Acid Usage in Osteogenesis Imperfecta Patients.

BACKGROUND: Osteogenesis Imperfecta (OI) usually causes an increased fracture burden and bone deformity, with subsequent operations common. In addition to skeletal manifestations, there is a potential increase in bleeding susceptibility due to the increased frequency of orthopedic procedures, warranting investigation into methods to mitigate this risk. This study aims to evaluate the safety and efficacy of tranexamic acid (TXA) usage to reduce intraoperative blood loss in children with OI. We want to assess the potential benefits, risks, and complications involved with TXA use in this patient population. METHODS: TXA-receiving patients (cases) were matched 1:1 with non-TXA-receiving controls on the following criteria: age within 2 years, bone category, and OI Type. Descriptive statistics were used to summarize the data. Fisher Exact Test was performed to compare transfusion status between groups. A Wilcoxon Rank Sum test was performed to assess differences between the groups in days of stay, length of surgery, and estimated blood loss (EBL). All analyses were conducted using SAS version 9.4. P <0.05 was considered statistically significant. RESULTS: Our TXA-receiving population of 30 patients consisted of 11 females and 19 males. One patient was OI type I, 13 were OI type III, 14 were OI type IV, and 2 were categorized as Other (not Type I through Type IV). We found a significant difference in transfusion status ( P =0.02), with zero TXA patients requiring a transfusion compared with 20% of the control cases. There is also a significant difference in median EBL ( P =0.0004) between groups, with TXA patients having decreased intraoperative EBL (20 vs. 62.5 mL). There was also a difference in median days of postoperative stay between TXA-receiving and non-TXA-receiving patients ( P =0.001; 2.6 vs. 4 d). CONCLUSIONS: Our study concluded that TXA use in OI patients is associated with lower perioperative transfusions and intraoperative blood loss rates. These results support the standard usage of TXA in these patients to reduce intraoperative blood loss. LEVEL OF EVIDENCE: Level III.

Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

Medical Laboratory Science Student Outcomes Related to Curriculum Changes Made During COVID-19 Pandemic.

The COVID-19 pandemic forced many healthcare education programs to alter teaching methods, leading to a transition from face-to-face learning to distance learning. This study aimed to evaluate how curricular changes made during the COVID-19 pandemic may have influenced student performance in a medical laboratory science (MLS) program. MLS student exam scores, final course grades, and Board of Certification performance data were investigated to determine how changes made to curriculum and delivery influenced program outcomes for students completing the program before and during the COVID-19 pandemic at the University of Nebraska Medical Center. Self-reported responses to faculty survey questions explored curriculum changes and perception of student success. There were 24 instances in which scores between the two cohorts were statistically significant with only two of those demonstrating the COVID-19 cohort performed better. Four of six faculty indicated they felt there was a disconnect between theory and laboratory application for the COVID-19 academic year and students performed better in the pre-COVID-19 academic year. While there are benefits for asynchronous learning, the findings and perceptions of this study suggest that in-person learning and combining theory and laboratory components support the education of introductory courses.

Mortality Increased Among Hospitalized Patients with Cirrhosis Before and Following Different Waves of the COVID-19 Pandemic.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic disrupted patient care and worsened the morbidity and mortality of some chronic diseases. The impact of the COVID-19 pandemic on hospitalizations and outcomes in patients with cirrhosis both before and during different time periods of the pandemic has not been evaluated. AIMS: Describe characteristics of hospitalized patients with cirrhosis and evaluate inpatient mortality and 30-day readmission before and after the start of the COVID-19 pandemic. METHODS: Retrospective single-center cohort study of all hospitalized patients with cirrhosis from 2018 to 2022. Time periods within the COVID-19 pandemic were defined using reference data from the World Health Organization and Centers for Disease Control. Adjusted odds ratios from logistic regression were used to assess differences between periods. RESULTS: 33,926 unique hospitalizations were identified. Most patients were over age 60 years across all time periods of the pandemic. More Hispanic patients were hospitalized during COVID-19 than before COVID-19. Medicare and Medicaid are utilized less frequently during COVID-19 than before COVID-19. After controlling for age and gender, inpatient mortality was significantly higher during all COVID-19 periods except Omicron compared to before COVID-19. The odds of experiencing a 30-day readmission were 1.2 times higher in the pre-vaccination period compared to the pre-COVID-19 period. CONCLUSION: Inpatient mortality among patients with cirrhosis has increased during the COVID-19 pandemic compared to before COVID-19. Although COVID-19 infection may have had a small direct pathologic effect on the natural history of cirrhotic liver disease, it is more likely that other factors are impacting this population.

Effectiveness of E-learning on clinical application of dental injection anatomy via simulation manikins.

PURPOSE: E-learning is frequently integrated into dental education, yet little is known on the effectiveness of e-learning in both instilling foundational knowledge and facilitating translation of newly acquired knowledge and skill into clinical application. The objective of this study was to investigate the impact of learning modality on acquisition of knowledge and translation to clinical skill using objective feedback from oral anesthesia manikins and subjects' self-reported confidence scores. METHODS: This mixed-method study involved first year dental students (n = 52) who volunteered to participate in a learning intervention, simulation exercise, and survey in 2022. Students were randomly assigned to lecture (n = 26) or e-learning (n = 26) cohorts and then participated in the intervention, postintervention assessment, and a simulation to evaluate correct approaches for each dental block and attempts to success. RESULTS: All subjects scored significantly higher on post-intervention assessment compared to pre-intervention assessment (8.2 vs. 5.9; p < 0.0001) with no significant differences between intervention groups when comparing preintervention and postintervention scores. Furthermore, there were no significant differences between the two cohorts when comparing abilities to correctly approach each dental block or attempts to success. Finally, all students reported a significant increase in confidence in most categories following intervention and simulation, with no significant differences between lecture and e-learning cohorts. CONCLUSION: Our findings suggest students learning via e-learning are equally capable as those learning via lecture at demonstrating newly acquired knowledge and skill in both assessments and clinical simulations. Results support incorporating supplemental e-learning and oral anesthesia manikin exercises for students learning the anatomy of dental injections.

A retrospective analysis of immune checkpoint inhibitors in patients with preexisting organ dysfunction.

BACKGROUND: There are limited to no data regarding the use of immune checkpoint inhibitors (ICIs) in patients who have preexisting organ dysfunction because these patients are frequently excluded from clinical trials. The authors' objective was to evaluate the effects of ICIs in patients with chronic kidney disease (CKD), cirrhosis, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF). METHODS: Data were obtained retrospectively for patients older than 18 years with solid organ malignancies who received at least one dose of an ICI between January 1, 2015, and January 1, 2021, and had either CKD (n = 90), cirrhosis (n = 20), COPD (n = 142), or CHF (n = 82) before ICI initiation at the authors' institution. Descriptive statistics were used to summarize patient characteristics, treatment characteristics, immune-related adverse events (IrAEs), and outcomes. An independent samples t-test or the Wilcoxon rank-sum test was used to assess differences in continuous variables; the χ2 test or the Fisher exact test was used to assess differences in categorical variables between patients with and without IrAEs. Progression-free survival (PFS) was assessed using Kaplan-Meier curves, and the log-rank test was used to assess differences in PFS. RESULTS: In all four cohorts, there were no statistically significant differences in patient characteristics, treatment characteristics, or outcomes, such as the number of hospitalizations and PFS, among those who experienced IrAEs compared with those who did not. In the CKD cohort, patients with IrAEs were significantly less likely to die than those without IrAEs (52% vs. 81% [p = .009] for all patients; 53% vs. 83% [p = .008] for patients with stage II/III disease who received no definitive local treatment and patients with stage IV disease); this difference was not observed in the cirrhosis, COPD, or CHF cohorts. There was no statistically significant difference in the number of heart failure and COPD exacerbations during the receipt of ICIs in the CHF and COPD cohorts, respectively. The incidence and time to onset of IrAEs in this study appeared to be similar to those reported previously in clinical trials that excluded patients with significant comorbidities. CONCLUSIONS: The current results demonstrate that ICIs are well tolerated by patients who have preexisting organ dysfunction.

Outcomes of Pediatric Osteogenesis Imperfecta Patients Requiring Port-a-Cath Placement for Long-Term Vascular Access.

Intravenous (iv) bisphosphonates are widely used to treat the skeletal manifestations of osteogenesis imperfecta (OI). Obtaining peripheral iv access in pediatric patients with OI is often difficult and traumatic. Although this may be mitigated with surgically placed iv ports (port-a-caths), surgeons may be hesitant to perform this procedure on these children because of the lack of safety data. This study aims to gain better insight into the safety and efficacy of port-a-cath use in this population and identify risk factors for port-a-cath complications. In the present study, we conducted a retrospective cohort analysis of patient characteristics and the incidence of port-a-cath-related complications in children with OI. Fifty-three port-a-caths were placed in 29 children (21 males and 8 females). Of the 29 patients, most are OI type III (n = 18), followed by type I (n = 4), type IV (n = 4), and type V (n = 3). At the time of initial port-a-cath placement, the median age was 52 months (10-191 months), and the median weight was 7.9 kg (5.1-41.1 kg). Most patients (n = 20) weighed less than 10 kg during initial placement. Weight correlated significantly with OI type (p = 0.048), sex (p = 0.03), and vessel used (p = 0.02). Median initial port-a-cath longevity was 43 months (1-113 months), and we found no significant difference in port-a-cath longevity between sexes, OI types, or vessels used. Most patients (n = 19) required multiple port-a-cath placements. There is a significant difference (p = 0.02) between the number of placements and OI type, with type IV having more than type III. Port-a-cath removal was almost always due to mechanical complications (n = 19) but also for infection (n = 1) and malposition (n = 1). Eight patients still had their initial port-a-caths in place at the conclusion of this study. These findings indicate that complications associated with port-a-cath placement are mild and can be used to safely deliver iv bisphosphonates to pediatric OI patients. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Characteristics of pathologic complete response for locally advanced rectal cancer.

BACKGROUND: Neoadjuvant chemoradiation (NACRT) is the standard of care for locally advanced rectal cancers. The purpose of this study was to determine patient and tumor factors associated with a pathologic complete response (pCR). METHODS: The National Surgical Quality Improvement Program proctectomy-targeted database was utilized to identify all patients from 2016 to 2020 who underwent NACRT followed by proctectomy with curative intent for T3-4N0-2 rectal cancers. RESULTS: A total of 1891 patients were included, of which 253 (13.4%) demonstrated a pCR. Pretreatment N0 staging was associated with a higher rate of pCR (18.9%) when compared to N1 (6.7%) and N2 (6.7%) (p < 0.0001). Patients clinically staged at T3N0 had the highest rate of pCR (19.5%). Gender, age, race, weight, smoking status, and tumor height were not associated with pCR. CONCLUSIONS: Patients with cN0 disease were more likely to experience a pCR compared to cN1-2 patients. Tumor height relative to anal verge or patient demographics were not associated with pCR.

Hormone replacement therapy and COVID-19 outcomes in solid organ transplant recipients compared with the general population.

Exogenous estrogen is associated with reduced coronavirus disease (COVID) mortality in nonimmunosuppressed/immunocompromised (non-ISC) postmenopausal females. Here, we examined the association of estrogen or testosterone hormone replacement therapy (HRT) with COVID outcomes in solid organ transplant recipients (SOTRs) compared to non-ISC individuals, given known differences in sex-based risk in these populations. SOTRs ≥45 years old with COVID-19 between April 1, 2020 and July 31, 2022 were identified using the National COVID Cohort Collaborative. The association of HRT use in the last 24 months (exogenous systemic estrogens for females; testosterone for males) with major adverse renal or cardiac events in the 90 days post-COVID diagnosis and other secondary outcomes were examined using multivariable Cox proportional hazards models and logistic regression. We repeated these analyses in a non-ISC control group for comparison. Our study included 1135 SOTRs and 43 383 immunocompetent patients on HRT with COVID-19. In non-ISC, HRT use was associated with lower risk of major adverse renal or cardiac events (adjusted hazard ratio [aHR], 0.61; 95% confidence interval [CI], 0.57-0.65 for females; aHR, 0.70; 95% CI, 0.65-0.77 for males) and all secondary outcomes. In SOTR, HRT reduced the risk of acute kidney injury (aHR, 0.79; 95% CI, 0.63-0.98) and mortality (aHR, 0.49; 95% CI, 0.28-0.85) in males with COVID but not in females. The potentially modifying effects of immunosuppression on the benefits of HRT requires further investigation.

Age, ASA-status, and Changes in NSQIP Comorbidity Indices Reporting in Facial Fracture Repair.

OBJECTIVE: To evaluate the impact of age and the American Society of Anesthesiologists (ASA) classification on post operative outcomes as well as the changes in the National Surgical Quality Improvement Program (NSQIP) database reporting of comorbidity index variables in patients with facial fractures. METHODS: The NSQIP database was queried for facial fracture repair CPT codes between 2012 and 2019 and for modified Frailty Index (mFI) and modified Charlson Comorbidity Index (mCCI) variables between years 2006 and 2018. The predominant question analyzed two preoperative risk factors: patient and ASA classification. Chi-square analysis, Kruskal-Wallis, Mann-Whitney, Spearman correlation, and multivariable logistic regression were used to evaluate age and ASA classification with wound dehiscence, superficial surgical site infection (SSSI), deep wound infection (DWI), readmission status, and return to the OR. The reporting of indices variables was evaluated with descriptive statistics. CONCLUSION: In this large database with univariate analysis, patients with a higher ASA classification and older patients experience significantly increased risks of readmission, return to the OR, and longer hospital stays. On multivariate analyses, ASA classes II, III, and IV are independently associated with increased risk of readmission and return to the OR, while controlling for patient age. The reporting of all mFI and mCCI variables were consistent from 2006 to 2010, but after 2011, there has been inconsistent or absent reporting of variables, therefore, conclusions on the impact of comorbidities on facial fracture repair are unreliable. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2572-2577, 2023.

Effect of Nora virus infection on native gut bacterial communities of Drosophila melanogaster.

Gastrointestinal microflora is a key component in the maintenance of health and longevity across many species. In humans and mice, nonpathogenic viruses present in the gastrointestinal tract enhance the effects of the native bacterial microbiota. However, it is unclear whether nonpathogenic gastrointestinal viruses, such as Nora virus that infects Drosophila melanogaster, lead to similar observations. Longevity analysis of Nora virus infected (NV+) and uninfected (NV-) D. melanogaster in relationship to presence (B+) or absence (B-) of the native gut bacteria using four different treatment groups, NV+/B+, NV+/B-, NV-/B+, and NV-/B-, was conducted. Data from the longevity results were tested via Kaplan-Meier analysis and demonstrated that Nora virus can be detrimental to the longevity of the organism, whereas bacterial presence is beneficial. These data led to the hypothesis that gastrointestinal bacterial composition varies from NV+ to NV- flies. To test this, NV+ and NV- virgin female flies were collected and aged for 4 days. Surface sterilization followed by dissections of the fat body and the gastrointestinal tract, divided into crop (foregut), midgut, and hindgut, were performed. Ribosomal 16S DNA samples were sequenced to determine the bacterial communities that comprise the microflora in the gastrointestinal tract of NV+ and NV- D. melanogaster. When analyzing operational taxonomic units (OTUs), the data demonstrate that the NV+ samples consist of more OTUs than NV- samples. The NV+ samples were both more rich and diverse in OTUs compared to NV-. When comparing whole body samples to specific organs and organ sections, the whole fly was more diverse in OTUs, whereas the crop was the most rich. These novel data are pertinent in describing where Nora virus infection may be occurring within the gastrointestinal tract, as well as continuing discussion between the relationship of persistent viral and bacterial interaction.