Top Ten Tips Palliative Care Clinicians Should Know About Diagnosing, Categorizing, and Addressing Fatigue.

Fatigue is a multifactorial symptom that is commonly faced by patients with cancer, chronic disease, and other serious illnesses. Fatigue causes suffering across biopsychosocial domains and affects patients and their loved ones. In this article, a consortium of professionals across cancer care, physical therapy, exercise, pharmacy, psychiatry, and palliative medicine offers tips and insights on evaluating, categorizing, and addressing fatigue in the setting of serious illness. The comprehensive approach to managing fatigue underscores the importance of collaborative efforts characteristic of interdisciplinary palliative care. Prioritizing screening, diagnosing, and treating fatigue is crucial for enhancing patients' and families' overall quality of life.

Association between echocardiographic features, troponin levels, and survival time in hospitalized COVID-19 patients with cardiovascular events.

Introduction: This study aims to explore the predictive roles of echocardiographic parameters and biomarkers in determining outcomes among hospitalized COVID-19 patients experiencing cardiovascular events. Methods: A retrospective cohort study was conducted involving 49 COVID-19 patients who encountered cardiovascular events during hospitalization and underwent echocardiography. Our findings revealed notable associations between echocardiographic parameters and survival time. Results: A decrease in left ventricular ejection fraction (LVEF) of 10% was linked to a 20% reduction in survival time (TR: 0.80, 95% CI: 0.67 - 0.96, p = .017). Similarly, an increase in left ventricular (LV) volume by 10 mL was associated with a 9% decrease in survival time (TR: 0.91, 95% CI: 0.84 - 0.98, p = .011). Moreover, an increase in left atrial (LA) volume by 10 mL corresponded to an 8% decrease in survival time (TR: 0.92, 95% CI: 0.86 - 0.99, p = .026). Additionally, each 1 cm increase in right ventricular (RV) diameter was linked to a 22% reduction in survival time (TR: 0.78, 95% CI: 0.61 - 0.99, p = .043). Furthermore, a 10 mL increase in right atrial (RA) volume was associated with a 12% decrease in survival time (TR: 0.88, 95% CI: 0.78 - 0.98, p = .017). Notably, a tenfold rise in troponin levels was linked to a 33% decrease in survival time (TR: 0.67, 95% CI: 0.48 - 0.93, p = .014). Conclusions: Our study emphasizes the significant associations between various echocardiographic parameters and troponin levels with reduced survival time among COVID-19 patients experiencing cardiovascular events. These findings highlight the potential utility of echocardiography and troponin assessment in predicting outcomes and guiding management strategies in this patient population.

Baseline total brain volume predicts changes in quality of life and overall survival after cranial radiotherapy in older patients with glioblastoma: Results from the prospective BRITER study.

Background: Short-course partial brain radiotherapy ± chemotherapy for older patients with GBM extends survival but there is no validated evidence for prediction of individual risk of acute radiotherapy-related side effects. Methods: This prospective multicentre observational trial recruited patients with newly diagnosed GBM aged ≥65 planned for cranial radiotherapy. Baseline MRI scans were analyzed for markers of brain resilience including relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)) and their relationship to change in quality of life (QoL). Results: 126 patients enrolled: mean age 72 years (range 65-83). 77% had debulking surgery. 79% received radiotherapy with concurrent TMZ, and 21% received palliative radiotherapy alone. The median OS was 10.7 months. After accounting for age, sex, treatment, and baseline MoCA score, there was a relationship between baseline CSF:TIV and change in QoL score at 8 weeks post treatment. For each unit point of increase in CSF:TIV, there was a corresponding decrease in QoL score of 1.72 (95% CI -3.24 to -0.19 P = .027). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow-up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV was related to the risk of non-attendance (OR 1.35, 95% CI 1.01 to 1.80, P = .042). Cox regression models showed baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19 to 1.66, P < .001). Conclusions: This study provides evidence to support the use of an imaging biomarker to help assess the risk:benefit ratio for radiotherapy.

Prescription Opioid Use Disorder Among Adults Reporting Prescription Opioid Use With or Without Misuse in the United States.

Objective: We examined prescription related opioid use disorder (POUD) prevalence, individual symptoms, severity, characteristics, and treatment by prescription opioid misuse status among adults with prescription opioid use.Methods: Cross-sectional study using nationally representative data from 47,291 adults aged ≥18 years who participated in the 2021 National Survey on Drug Use and Health. Past-year POUD used DSM-5 criteria.Results: Among US adults with past-year prescription opioid use, 12.1% (95% CI, 11.1%-13.1%) misused prescription opioids, and 7.0% (95% CI, 6.2%-8.9%) had POUD. Among adults with POUD, 62.0% (95% CI, 56.7%-67.2%) reported no prescription opioid misuse, including 49.1% (95% CI, 43.5%-54.7%) with mild POUD, 11.0% (95% CI, 6.5%-15.4%) with moderate POUD, and 1.9% (95% CI, 0.6%-3.2%) with severe POUD. Prevalence of POUD was 4.5 times higher (prevalence ratio = 4.5, 95% CI, 3.6-5.6) among those reporting prescription opioid misuse (22.0%, 95% CI, 18.6%-25.8%) than those reporting use without misuse (4.9%, 95% CI, 4.2%-5.7%). Among adults reporting prescription opioid use without misuse, high POUD prevalence was found for those with ≥3 emergency department visits (16.4%, 95% CI, 11.5%-23.0%), heroin use/use disorder (17.1%, 95% CI, 5.2%-43.8%), prescription sedative/ tranquilizer use disorder (36.2%, 95% CI, 23.6%-51.1%), and prescription stimulant use disorder (21.8%, 95% CI, 11.0%-38.7%).Conclusions: Moderate-to-severe POUD is more frequent among adults who report misusing prescription opioids. However, 62% of adults with POUD do not report prescription opioid misuse, suggesting that adults who are treated with prescription opioids and report no misuse could be at risk for developing POUD. Results highlight the need to screen for and treat POUD among adults taking prescription opioids regardless of whether they report prescription opioid misuse.

Standard or high dose chemoradiotherapy, with or without the protease inhibitor nelfinavir, in patients with locally advanced pancreatic cancer: The phase 1/randomised phase 2 SCALOP-2 trial.

BACKGROUND: The multi-centre two-stage SCALOP-2 trial (ISRCTN50083238) assessed whether dose escalation of consolidative chemoradiotherapy (CRT) or concurrent sensitization using the protease inhibitor nelfinavir improve outcomes in locally advanced pancreatic cancer (LAPC) following four cycles of gemcitabine/nab-paclitaxel. METHODS: In stage 1, the maximum tolerated dose (MTD) of nelfinavir concurrent with standard-dose CRT (50.4 Gy in 28 fractions) was identified from a cohort of 27 patients. In stage 2, 159 patients were enrolled in an open-label randomized controlled comparison of standard versus high dose (60 Gy in 30 fractions) CRT, with or without nelfinavir at MTD. Primary outcomes following dose escalation and nelfinavir use were respectively overall survival (OS) and progression free survival (PFS). Secondary endpoints included health-related quality of life (HRQoL). RESULTS: High dose CRT did not improve OS (16.9 (60 % confidence interval, CI 16.2-17.7) vs. 15.6 (60 %CI 14.3-18.2) months; adjusted hazard ratio, HR 1.13 (60 %CI 0.91-1.40; p = 0.68)). Similarly, median PFS was not improved by nelfinavir (10.0 (60 %CI 9.9-10.2) vs. 11.1 (60 %CI 10.3-12.8) months; adjusted HR 1.71 (60 %CI 1.38-2.12; p = 0.98)). Local progression at 12 months was numerically lower with high-dose CRT than with standard dose CRT (n = 11/46 (23.9 %) vs. n = 15/45 (33.3 %)). Neither nelfinavir nor radiotherapy dose escalation impacted on treatment compliance or grade 3/4 adverse event rate. There were no sustained differences in HRQoL scores between treatment groups over 28 weeks post-treatment. CONCLUSIONS: Dose-escalated CRT may improve local tumour control and is well tolerated when used as consolidative treatment in LAPC but does not impact OS. Nelfinavir use does not improve PFS.

A baseline epidemiological survey for malaria and schistosomiasis reveals an alarming burden in primary schools despite ongoing control in Chikwawa District, southern Malawi.

Our study rationale was to establish contemporary epidemiological data on malaria and schistosomiasis among school-going children in Chikwawa District before future environmental changes associated with the Shire Valley Transformation Programme occurred. Our cross-sectional surveys tested 1134 children from 21 government-owned primary schools (approximately 50 children per school); rapid diagnostic tests for malaria (Humasis Pf/PAN) and intestinal schistosomiasis (urine-Circulating Cathodic Antigen) were used, with urine reagents strips and egg-filtration with microscopy for urogenital schistosomiasis. All infected children were treated with an appropriate dose of Lonart® (for malaria) and/or Cesol® (for schistosomiasis). Across 21 schools the overall prevalence was 9.7% (95% CI: 8.8-10.6%) for malaria, 1.9% (95% CI: 1.4-2.3%) for intestinal schistosomiasis, and 35.0% (95% CI: 33.6-36.5%) for egg-patent urogenital schistosomiasis. The prevalence of co-infection of malaria with urogenital schistosomiasis was 5.5% (95% CI: 4.8-6.2%). In a third of the schools, the prevalence of malaria and urogenital schistosomiasis was above national averages of 10.5% and 40-50%, respectively, with two schools having maxima of 36.8% and 84.5%, respectively. Set against a background of ongoing control, our study has revealed an alarming burden of malaria and schistosomiasis in southern Malawi. These findings call for an immediate mitigating response that significantly bolsters current control interventions to better safeguard children's future health.

Small dams drive Anopheles abundance during the dry season in a high malaria burden area of Malawi.

This study explores the influence of small dams on the exposure to malaria vectors during the dry season in Kasungu district, Malawi, an area recently identified as high priority for malaria interventions by the National Malaria Control Programme. Small dam impoundments provide communities with a continuous supply of water for domestic and agricultural activities across sub-Saharan Africa and are considered vital to food security and climate change resilience. However, these permanent water bodies also create ideal breeding sites for mosquitoes in typically arid landscapes. The study focuses on a specific dam impoundment and its vicinity, aiming to assess its spatial and temporal influence on indoor vector densities. From May to August 2021, CDC light traps were used to measure indoor mosquito densities for two consecutive nights per month in three communities located at increasing distances from the dam (0, ~1 and ~2 km). Simultaneously, drone imagery was captured for each community, enabling the identification of additional standing water within approximately 400 m of selected households. Larval sampling was carried out within the impoundment periphery and in additional water bodies identified in the drone imagery. Generalised linear mixed models (GLMMs) were employed to analyse the indoor Anopheles abundance data, estimating the effects of household structure (open/closed eaves), month, temperature and water proximity on malaria vector exposure. Throughout 685 trapping nights, a total of 1256 mosquitoes were captured, with 33% (412) being female Anopheles. Among these, 91% were morphologically identified as Anopheles funestus s.l., and 5% as Anopheles gambiae s.l. Catches progressively decline in each consecutive trapping month as the environment became drier. This decline was much slower in Malangano, the community next to the dam, with abundance being notably higher in June and July. Further, the majority of An. gambiae s.l. were caught in May, with none identified in July and August. Anopheles larvae were found both in the impoundment and other smaller water bodies such as irrigation wells in each survey month; however, the presence of these smaller water bodies did not have a significant impact on adult female mosquito catches in the GLMM. The study concludes that proximity to the dam impoundment was the primary driver of differences between survey communities with the abundance in Chikhombwe (~1 km away) and Chiponde (~2 km away) being 0.35 (95% confidence interval [CI], 0.19-0.66) and 0.28 (95% CI, 0.16-0.47) lower than Malangano, respectively, after adjusting for other factors. These findings underscore the importance of targeted interventions, such as larval source management or housing improvements, near small dams to mitigate malaria transmission risks during the dry season. Further research is needed to develop cost-effective strategies for vector control within and around these impoundments.

A Geometrically Flexible Three-Dimensional Nanocarbon.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

Neighborhood Resources Associated With Psychological Trajectories and Neural Reactivity to Reward After Trauma.

Importance: Research on resilience after trauma has often focused on individual-level factors (eg, ability to cope with adversity) and overlooked influential neighborhood-level factors that may help mitigate the development of posttraumatic stress disorder (PTSD). Objective: To investigate whether an interaction between residential greenspace and self-reported individual resources was associated with a resilient PTSD trajectory (ie, low/no symptoms) and to test if the association between greenspace and PTSD trajectory was mediated by neural reactivity to reward. Design, Setting, and Participants: As part of a longitudinal cohort study, trauma survivors were recruited from emergency departments across the US. Two weeks after trauma, a subset of participants underwent functional magnetic resonance imaging during a monetary reward task. Study data were analyzed from January to November 2023. Exposures: Residential greenspace within a 100-m buffer of each participant's home address was derived from satellite imagery and quantified using the Normalized Difference Vegetation Index and perceived individual resources measured by the Connor-Davidson Resilience Scale (CD-RISC). Main Outcome and Measures: PTSD symptom severity measured at 2 weeks, 8 weeks, 3 months, and 6 months after trauma. Neural responses to monetary reward in reward-related regions (ie, amygdala, nucleus accumbens, orbitofrontal cortex) was a secondary outcome. Covariates included both geocoded (eg, area deprivation index) and self-reported characteristics (eg, childhood maltreatment, income). Results: In 2597 trauma survivors (mean [SD] age, 36.5 [13.4] years; 1637 female [63%]; 1304 non-Hispanic Black [50.2%], 289 Hispanic [11.1%], 901 non-Hispanic White [34.7%], 93 non-Hispanic other race [3.6%], and 10 missing/unreported [0.4%]), 6 PTSD trajectories (resilient, nonremitting high, nonremitting moderate, slow recovery, rapid recovery, delayed) were identified through latent-class mixed-effect modeling. Multinominal logistic regressions revealed that for individuals with higher CD-RISC scores, greenspace was associated with a greater likelihood of assignment in a resilient trajectory compared with nonremitting high (Wald z test = -3.92; P < .001), nonremitting moderate (Wald z test = -2.24; P = .03), or slow recovery (Wald z test = -2.27; P = .02) classes. Greenspace was also associated with greater neural reactivity to reward in the amygdala (n = 288; t277 = 2.83; adjusted P value = 0.02); however, reward reactivity did not differ by PTSD trajectory. Conclusions and Relevance: In this cohort study, greenspace and self-reported individual resources were significantly associated with PTSD trajectories. These findings suggest that factors at multiple ecological levels may contribute to the likelihood of resiliency to PTSD after trauma.

Corrigendum to "Androgen Deprivation and Radiotherapy with or Without Docetaxel for Localized High-risk Prostat Cancer: Long-term Follow-up from the Randomized NRG Oncology RTOG 0521 Trial" [Eur. Eurol. 84(2) (2023) 156-163].

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer. OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT. DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS). RESULTS AND LIMITATIONS: After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70-1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73-1.14), DM (HR = 0.84, 95% CI 0.73-1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74-1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm. CONCLUSIONS: After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers. PATIENT SUMMARY: No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate ± docetaxel.

Overdose, Behavioral Health Services, and Medications for Opioid Use Disorder After a Nonfatal Overdose.

Importance: Recognizing and providing services to individuals at highest risk for drug overdose are paramount to addressing the drug overdose crisis. Objective: To examine receipt of medications for opioid use disorder (MOUD), naloxone, and behavioral health services in the 12 months after an index nonfatal drug overdose and the association between receipt of these interventions and fatal drug overdose. Design, Setting, and Participants: This cohort study was conducted in the US from January 2020 to December 2021 using claims, demographic, mortality, and other data from the Centers for Medicare & Medicaid Services, the Centers for Disease Control and Prevention, and other sources. The cohort comprised Medicare fee-for-service beneficiaries aged 18 years or older with International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes for a nonfatal drug overdose. Data analysis was performed from February to November 2023. Exposures: Demographic and clinical characteristics, substance use disorder, and psychiatric comorbidities. Main Outcomes and Measures: Receipt of MOUD, naloxone, and behavioral health services as well as subsequent nonfatal and fatal drug overdoses. Results: The cohort consisted of 136 762 Medicare beneficiaries (80 140 females [58.6%]; mean (SD) age of 68.2 [15.0] years) who experienced an index nonfatal drug overdose in 2020. The majority of individuals had Hispanic (5.8%), non-Hispanic Black (10.9%), and non-Hispanic White (78.8%) race and ethnicity and lived in metropolitan areas (78.9%). In the 12 months after their index nonfatal drug overdose, 23 815 beneficiaries (17.4%) experienced at least 1 subsequent nonfatal drug overdose and 1323 (1.0%) died of a fatal drug overdose. Opioids were involved in 72.2% of fatal drug overdoses. Among the cohort, 5556 (4.1%) received any MOUD and 8530 (6.2%) filled a naloxone prescription in the 12 months after the index nonfatal drug overdose. Filling a naloxone prescription (adjusted odds ratio [AOR], 0.70; 95% CI, 0.56-0.89), each percentage of days receiving methadone (AOR, 0.98; 95% CI, 0.98-0.99) or buprenorphine (AOR, 0.99; 95% CI, 0.98-0.99), and receiving behavioral health assessment or crisis services (AOR, 0.25; 95% CI, 0.22-0.28) were all associated with reduced adjusted odds of fatal drug overdose in the 12 months after the index nonfatal drug overdose. Conclusions and Relevance: This cohort study found that, despite their known association with reduced risk of a fatal drug overdose, only a small percentage of Medicare beneficiaries received MOUD or filled a naloxone prescription in the 12 months after a nonfatal drug overdose. Efforts to improve access to behavioral health services; MOUD; and overdose-prevention strategies, such as prescribing naloxone and linking individuals to community-based health care settings for ongoing care, are needed.

Treatment strategy and clinical outcomes of surgically managed hip periprosthetic fractures: analysis from a high-volume centre.

BACKGROUND: Hip periprosthetic fractures (PPF) after total hip arthroplasty (THA) are becoming increasingly prevalent. Their management is secondary to the fracture type and the stability of the implant. This study aimed to provide the outcomes of operatively managed PPF from a high-volume centre to help guide future decision making. METHODS: This was a retrospective study of prospectively collected data from January 2008 to January 2021. Patient demographics, implant specific details, and fixation strategy were collected. Complications including infection, reoperation, re-fracture, re-revision, were collected. Short-term mortality was evaluated at 3 months and 1 year. P-values <0.05 were considered significant. RESULTS: 282 surgically managed PPF were identified. Vancouver B2 were predominant in 52% of the cases. Revision alone and revision with additional fixation were the most frequent strategies in 168 cases (60%). Complications requiring reoperation occurred in 20% of the cases, with infection as the most frequent (8.5%). Mortality rate was 7.8% at 3 months and 15.7% at 1 year, with significantly lower rates in B2 type. B2 fractures treated with cemented stems had a significantly lower 1-year mortality than distal fit revisions. CONCLUSIONS: PPF is associated with a high complication rate. Revision alone and revision with additional fixation remain the preferred method in B2/B3 type fractures, however, cemented revision can yield similar outcomes with lower short-term mortality. Considering the high-risk elderly and frail category of patients, a multidisciplinary team is necessary to improve outcomes and reduce mortality.

A Second Space Age Spanning Omics, Platforms, and Medicine Across Orbits.

The recent acceleration of commercial, private, and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit (LEO), concomitant with the highest-ever number of crewed missions entering space and preparations for exploration-class (>1 year) missions. Such rapid advancement into space from many new companies, countries, and space-related entities has enabled a"Second Space Age." This new era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews. The applications of these biomedical technologies and algorithms are diverse, encompassing multi-omic, single-cell, and spatial biology tools to investigate human and microbial responses to spaceflight. Additionally, they extend to the development of new imaging techniques, real-time cognitive assessments, physiological monitoring, and personalized risk profiles tailored for astronauts. Furthermore, these technologies enable advancements in pharmacogenomics (PGx), as well as the identification of novel spaceflight biomarkers and the development of corresponding countermeasures. In this review, we highlight some of the recent biomedical research from the National Aeronautics and Space Administration (NASA), Japan Aerospace Exploration Agency (JAXA), European Space Agency (ESA), and other space agencies, and also detail the commercial spaceflight sector's (e.g. SpaceX, Blue Origin, Axiom, Sierra Space) entrance into aerospace medicine and space biology, the first aerospace medicine biobank, and the myriad upcoming missions that will utilize these tools to ensure a permanent human presence beyond LEO, venturing out to other planets and moons.

Advances in diagnosis and management of cancer of the esophagus.

Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, with most patients presenting with late stage disease.2 Novel strategies to improve early detection of the respective precursor lesions, squamous dysplasia, and Barrett's esophagus offer the potential to improve outcomes. The introduction of a limited number of biologic agents, as well as immune checkpoint inhibitors, is resulting in improvements in the systemic treatment of locally advanced and metastatic esophageal cancer. These developments, coupled with improvements in minimally invasive surgical and endoscopic treatment approaches, as well as adaptive and precision radiotherapy technologies, offer the potential to improve outcomes still further. This review summarizes the latest advances in the diagnosis and management of esophageal cancer, and the developments in understanding of the biology of this disease.

Stepped Palliative Care for Patients With Advanced Lung Cancer: A Randomized Clinical Trial.

Importance: Despite the evidence for early palliative care improving outcomes, it has not been widely implemented in part due to palliative care workforce limitations. Objective: To evaluate a stepped-care model to deliver less resource-intensive and more patient-centered palliative care for patients with advanced cancer. Design, Setting, and Participants: Randomized, nonblinded, noninferiority trial of stepped vs early palliative care conducted between February 12, 2018, and December 15, 2022, at 3 academic medical centers in Boston, Massachusetts, Philadelphia, Pennsylvania, and Durham, North Carolina, among 507 patients who had been diagnosed with advanced lung cancer within the past 12 weeks. Intervention: Step 1 of the intervention was an initial palliative care visit within 4 weeks of enrollment and subsequent visits only at the time of a change in cancer treatment or after a hospitalization. During step 1, patients completed a measure of quality of life (QOL; Functional Assessment of Cancer Therapy-Lung [FACT-L]; range, 0-136, with higher scores indicating better QOL) every 6 weeks, and those with a 10-point or greater decrease from baseline were stepped up to meet with the palliative care clinician every 4 weeks (intervention step 2). Patients assigned to early palliative care had palliative care visits every 4 weeks after enrollment. Main Outcomes and Measures: Noninferiority (margin = -4.5) of the effect of stepped vs early palliative care on patient-reported QOL on the FACT-L at week 24. Results: The sample (n = 507) mostly included patients with advanced non-small cell lung cancer (78.3%; mean age, 66.5 years; 51.4% female; 84.6% White). The mean number of palliative care visits by week 24 was 2.4 for stepped palliative care and 4.7 for early palliative care (adjusted mean difference, -2.3; P < .001). FACT-L scores at week 24 for the stepped palliative care group were noninferior to scores among those receiving early palliative care (adjusted FACT-L mean score, 100.6 vs 97.8, respectively; difference, 2.9; lower 1-sided 95% confidence limit, -0.1; P < .001 for noninferiority). Although the rate of end-of-life care communication was also noninferior between groups, noninferiority was not demonstrated for days in hospice (adjusted mean, 19.5 with stepped palliative care vs 34.6 with early palliative care; P = .91). Conclusions and Relevance: A stepped-care model, with palliative care visits occurring only at key points in patients' cancer trajectories and using a decrement in QOL to trigger more intensive palliative care exposure, resulted in fewer palliative care visits without diminishing the benefits for patients' QOL. While stepped palliative care was associated with fewer days in hospice, it is a more scalable way to deliver early palliative care to enhance patient-reported outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03337399.

Preliminary Outcomes of Scapholunate Ligament Augmentation with Internal Brace Technique.

Purpose: Injury to the scapholunate (SL) interosseous ligament (SLIL) is a common cause of carpal instability. Internal brace augmentation has been used in various ligament repair procedures; however, further investigation of its outcomes in hand surgery is needed. This study aimed to examine outcomes for patients who underwent SLIL repair with internal brace augmentation. Methods: Patients who underwent SLIL repair with the internal brace technique and had at least 1 year of follow-up were contacted. Available patients returned for an in-person evaluation with new radiographs and physical examination. If patients could not be contacted but had x-rays and physical examinations performed at greater than 1 year after surgery, these data were collected from their medical records. Participating patients completed the QuickDASH and Patient-Rated Wrist Evaluation surveys and rated their satisfaction with the surgery. Outcomes assessed included wrist range of motion, grip strength, scaphoid shift test, SL gap, SL angle, and radiographic evidence of radiocarpal arthritis. Results: We collected outcomes for 14 SLIL repairs among 13 patients (12 male). Mean length of the follow-up was 41 months (n = 14, 17-64). Mean QuickDASH and Patient-Rated Wrist Evaluation scores were 6.1 (0-43.2) and 9.6 (0-65), respectively. Radiographic measurements remained stable from immediate to latest follow-up, and no radiocarpal arthritic changes were noted. However, SL gap decreased from a mean of 5.33 mm (3.4-6.7) before surgery to 3.34 mm (2-4.6) at the latest follow-up, and SL angle decreased from a mean of 79.5° (67°-97°) before surgery to 67.3° (51°-85°) at the latest follow-up. All scaphoid shift tests were stable. Conclusions: Therefore, SL internal brace augmentation has favorable short-term results with improvements in pain, function, satisfaction, and carpal alignment at greater than 1 year postoperatively. This technique can be an effective option for the management of SL instability in the short term. Type of study/level of evidence: Therapeutic IV.

Catalytic Upgrading of a Mixed Hydroxy Acid Feedstock Derived from Kraft Black Liquor.

Lignocellulosic feedstocks are widely studied for sustainable liquid fuel and chemical production. The pulp and paper industry generates large amounts of kraft black liquor (BL) from which a high volume of hydroxy acids (HAs) can be separated for further catalytic processing. Here, we explore the catalytic upgrading of HAs, including the conversion of (1) a model HA, gluconic acid; (2) a model mixture of HAs, and (3) a real mixture of HAs derived from kraft BL on M/Nb2O5 (M = Pd, Pt, Rh, and Ru). The hydrodeoxygenation of model gluconic acid reveals that "volatile" carboxylic acids (mainly C2 and C3), levulinic acid, and cyclic esters are significant products over all the catalysts, with Pd/Nb2O5 showing superior activity and selectivity toward valuable intermediates. The model mixture of HAs shows a wide range of reactivity over the supported metal catalyst, with the product selectivity strongly correlating to reaction temperature. Utilizing a 0.25% Pd/Nb2O5 catalyst, a real mixture of HAs derived from kraft BL is successfully dehydroxylated to produce a mixture rich in C3-C8 carboxylic acids that may be amenable for further upgrading, e.g., catalytically to ketones with high carbon chain lengths. Despite the feedstock complexity, we selectively cleaved the C-OH bonds of HAs, while successfully preserving most of the -COOH groups and minimizing C-C and C=O bond scission reactions under the operating conditions tested. The BL-derived HA stream is thus proposed to be a suitable platform for producing mixed carboxylic acid products from an overoxygenated byproduct feed.

Emergency department staff compassion is associated with lower fear of enacted stigma among patients with opioid use disorder.

OBJECTIVES: Fear of enacted stigma (fear of discrimination or being treated unfairly) is associated with decreased health care-seeking behaviors among patients with opioid use disorder (OUD). We sought to describe the prevalence of fear of enacted stigma among patients presenting to the emergency department (ED) with OUD and to test whether experiencing greater compassion from ED staff is associated with lower fear of enacted stigma. METHODS: We conducted a cross-sectional study in the ED of an academic medical center between February and August 2023. We included adult patients with OUD presenting to the ED and assessed patient experience of compassion from ED staff using a previously validated 5-item compassion measure (score range 5-20). The primary outcome measure was fear of enacted stigma in the ED, measured using the validated 9-item subscale of the Substance Abuse Self-Stigma Scale (score range 9-45). RESULTS: Of the 116 subjects enrolled, 97% (95% confidence interval [CI] 91%-99%) reported some degree of stigma, with a median (interquartile range) score of 23 (16-31). In a multivariable model adjusting for potential confounders, patient experience of greater ED compassion was independently associated with lower fear of enacted stigma, ß = -0.66 (95% CI -1.03 to -0.29), suggesting that every 1-point increase in the 5-item compassion measure score is associated with a 0.66-point decrease in the fear of enacted stigma score. CONCLUSIONS: Among ED patients with OUD, fear of enacted stigma is common. Patient experience of compassion from ED staff is associated with lower fear of enacted stigma. Future research is warranted to test if interventions aimed at increasing compassion from ED staff reduce patient fear of enacted stigma among patients with OUD.