Clinical predictive factors of pathologic complete response in locally advanced rectal cancer

Background: Predictive factors of pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) are still not identified. The purpose of this study was to define them. Materials and Methods: Data from consecutive LARC patients treated between January 2008 and June 2014 at our Institution were included in the analysis. All patients were treated with a long course of nCRT. Demographics, initial diagnosis and tumor extension details, as well as treatment modalities characteristics were included in the univariate and logistic regression analysis. Results: In total 99 patients received nCRT, of whom 23 patients (23.2%) achieved pCR. Patients with and without pCR were similar in term of age, sex, comobidities, BMI and tumor characteristics. Multivariate logistic regression indicated that pre-treatment tumor size <= 5 cm was a significant predictor for pCR (p = 0.035), whereas clinical N stage only showed a positive trend (p = 0.084). Conclusions: Tumor size at diagnosis could be used to predict pCR, and thus to individualize therapy in LARC patients management. Validation in other studies is needed

Exploring the Threats of Dams and Ocean Conditions: In-River Movements and Ocean Growth of Atlantic Salmon (Salmo salar) from Maine\u27s Rivers

Substantial declines of anadromous Atlantic Salmon Salmo salar have occurred throughout the range of the species, with many populations at the southern extent of the distribution being extirpated or endangered. While Maine is the last state in the country where adult Atlantic Salmon return to rivers each year to spawn, numbers have decreased dramatically in recent decades, with typically less than 2,000 spawners returning to all Maine\u27s rivers combined. The complex life history of this species, which involves a juvenile freshwater phase followed by a marine phase that can last one to five years before returning to freshwater to spawn has exposed Atlantic Salmon to a series of threats that have contributed to their continued decline. These threats include, among others, dams and changing ocean conditions that can influence marine mortality. This thesis focuses on those two threats by using radio telemetry to assess upstream passage of adult salmon in the lower Penobscot River and scale analysis to interpret ocean growth patterns in relation to ocean conditions. The Penobscot River Restoration Project (PRRP), completed in 2016, involved an extensive plan of dam removal, increases in hydroelectric capacity, and fish passage modifications to increase habitat access for diadromous species. As part of the PRRP, Great Works (rkm 59) and Veazie (rkm 46) Dams were removed, making Milford Dam (rkm 61) the first impediment to federally endangered Atlantic Salmon and other diadromous species. In 2014 and 2015, a total of 73 adult salmon were radio-tagged to track their upstream movements through the Penobscot River to assess potential delays at 1) the dam remnants, 2) the confluence of the Stillwater Branch and the main stem of the Penobscot River below the impassable Orono Dam, and 3) the Milford Dam fish lift (installed in 2014). Movement rates through the dam remnants and the Stillwater confluence were comparable to open river reaches. Passage efficiency of the fish lift was high in both years (95 and 100%). However, fish experienced long delays at Milford Dam, with approximately 1/3 of fish taking over a week to pass in each year. Telemetry indicates most fish locate the fishway entrance within 5 hours of arrival and were observed at the entrance at all hours of the day. These data indicate that overall transit times through the lower river were comparable before and after changes to the Penobscot River due to the substantial delays seen at Milford Dam fish lift. The results of this study show that while adult Atlantic Salmon locate the new fish lift entrance quickly, passage of these fish was significantly delayed under 2014-2015 operations. Prior to returning to spawn, Maine\u27s Atlantic Salmon typically spend one or two years at sea feeding. While both one sea winter (1SW) and two sea winter (2SW) spawner numbers for the North American stocks have declined since the 1950s, the decline has been most severe in 2SW spawners. The first months at sea are considered a period of high mortality. However, early ocean mortality alone cannot explain the more pronounced decline of 2SW spawners, suggesting that the second year at sea may be more critical than previously thought. Angler and state agency collected scales from 1946 to 2013 from the five eastern Maine rivers were used to estimate smolt age and ocean age of returning adults. Additionally, seasonal growth rates of maiden 2SW spawners were estimated using intercirculi measurements and linear back-calculation methods. Generalized linear models (Gaussian family, log link function) were used to investigate the influence of average sea surface temperature (SST), accumulated thermal units (ATUs), the Atlantic Multidecadal Oscillation (AMO) and North Atlantic Oscillation (NAO) indices, smolt age, smolt length (FL), and post-smolt growth on growth rate during the oceanic migration of North American Atlantic Salmon. Results suggest that different factors influence salmon growth throughout their oceanic migration, and previous growth can be a strong predictor of future size. Growth was negatively impacted by the phase of the AMO, which has been linked to salmon abundance trends, in the late winter and early spring following the post-smolt period. This is likely when the 1SW and 2SW stock components separate and these results suggest that this period could play a role in the disproportionate decline in 2SW spawners

COVID-19 Impact on Acute Ischemic Stroke Treatment at 9 Comprehensive Stroke Centers across Los Angeles.

OBJECTIVE: To describe the impact of COVID-19 on acute cerebrovascular disease care across 9 comprehensive stroke centers throughout Los Angeles County (LAC). METHODS: Volume of emergency stroke code activations, patient characteristics, stroke severity, reperfusion rates, treatment times, and outcomes from February 1 to April 30, 2020, were compared against the same time period in 2019. Demographic data were provided by each participating institution. RESULTS: There was a 17.3% decrease in stroke code activations across LAC in 2020 compared to 2019 (1,786 vs. 2,159, respectively, χ2 goodness of fit test p &lt; 0.0001) across 9 participating comprehensive stroke centers. Patients who did not receive any reperfusion therapy decreased by 16.6% in 2020 (1,527) compared to 2019 (1,832). Patients who received only intravenous thrombolytic (IVT) therapy decreased by 31.8% (107 vs. 157). Patients who received only mechanical thrombectomy (MT) increased by 3% (102 vs. 99). Patients who received both IVT and MT decreased by 31.8% (45 vs. 66). Recanalization treatment times in 2020 were comparable to 2019. CSCs serving a higher proportion of Latinx populations in the eastern parts of LAC experienced a higher incidence of MT in 2020 compared to 2019. Mild increase in stroke severity was seen in 2020 compared to 2019 (8.95 vs. 8.23, p = 0.046). A higher percentage of patients were discharged home in 2020 compared to 2019 (59.5 vs. 56.1%, p = 0.034), a lower percentage of patients were discharged to skilled nursing facility (16.1 vs. 20.7%, p = 0.0004), and a higher percentage of patients expired (8.6 vs. 6.3%, p = 0.008). CONCLUSION: LAC saw a decrease in overall stroke code activations in 2020 compared to 2019. Reperfusion treatment times remained comparable to prepandemic metrics. There has been an increase in severe stroke incidence and higher volume of thrombectomy treatments in Latinx communities within LAC during the pandemic of 2020. More patients were discharged home, less patients discharged to skilled nursing facilities, and more patients expired in 2020, compared to the same time frame in 2019

Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: −0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39–0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14–1.22; I² = 30.7%) and 1.20 (1.18–1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07–1.12; I² = 8.4%) and 1.14 (1.12–1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Association between multimorbidity and postoperative mortality in patients undergoing major surgery: a prospective study in 29 countries across Europe

BackgroundMultimorbidity poses a global challenge to healthcare delivery. This study aimed to describe the prevalence of multimorbidity, common disease combinations and outcomes in a contemporary cohort of patients undergoing major abdominal surgery.MethodsThis was a pre-planned analysis of a prospective, multicentre, international study investigating cardiovascular complications after major abdominal surgery conducted in 446 hospitals in 29 countries across Europe. The primary outcome was 30-day postoperative mortality. The secondary outcome measure was the incidence of complications within 30 days of surgery.ResultsOf 24,227 patients, 7006 (28.9%) had one long-term condition and 10,486 (43.9%) had multimorbidity (two or more long-term health conditions). The most common conditions were primary cancer (39.6%); hypertension (37.9%); chronic kidney disease (17.4%); and diabetes (15.4%). Patients with multimorbidity had a higher incidence of frailty compared with patients &lt;= 1 long-term health condition. Mortality was higher in patients with one long-term health condition (adjusted odds ratio 1.93 (95%CI 1.16-3.23)) and multimorbidity (adjusted odds ratio 2.22 (95%CI 1.35-3.64)). Frailty and ASA physical status 3-5 mediated an estimated 31.7% of the 30-day mortality in patients with one long-term health condition (adjusted odds ratio 1.30 (95%CI 1.12-1.51)) and an estimated 36.9% of the 30-day mortality in patients with multimorbidity (adjusted odds ratio 1.61 (95%CI 1.36-1.91)). There was no improvement in 30-day mortality in patients with multimorbidity who received pre-operative medical assessment.ConclusionsMultimorbidity is common and outcomes are poor among surgical patients across Europe. Addressing multimorbidity in elective and emergency patients requires innovative strategies to account for frailty and disease control. The development of such strategies, that integrate care targeting whole surgical pathways to strengthen current systems, is urgently needed for multimorbid patients. Interventional trials are warranted to determine the effectiveness of targeted management for surgical patients with multimorbidity

The Piver’s Island Coastal Observatory – a decade of weekly+ observations reveal the press and pulse of a changing temperate coastal marine system

Historically, oceanographic time-series have focused on long-term measurements of large open ocean gyres; yet, the coastal oceans, with their high productivity, tidal impacts, human feedbacks, and land-sea coupling, represent critical regions for predicting ocean dynamics and biogeochemistry under global change. The Piver’s Island Coastal Observatory (PICO) time-series, located in the second largest estuarine system on the US East Coast (Albemarle-Pamlico Sound), comprises more than a decade of weekly (or more frequent) measurements of core physical, chemical, and biological oceanographic variables. PICO provides insight into a coastal, mesotrophic ecosystem in an ecologically-diverse and biochemically-active region impacted by global change. Here, we report on a decade of observations focusing on pulse and press ecosystem changes. We observe strong mean annual cycles in environmental variables including temperature (10.1-28.9°C), pH (7.89-8.12), dissolved inorganic carbon (DIC: 1965 – 2088 µM), chlorophyll (2.54-5.77 mg Chl m-3), upon which are layered episodic disturbances (e.g., tropical cyclones) that dramatically and persistently (&gt;1 month) impact this ecosystem. Among other variables, long term trends in pH (-0.004 ± 0.001 y-1; p&lt;0.01), DIC (-9.8 ± 1.5 µM y -1; p&lt;0.01) and chlorophyll (-0.17 ± 0.02 µg L-1 y-1; p&lt;0.01) are exceeding those observed in the open ocean, suggesting an ecosystem in flux. These analyses provide a benchmark for future studies of the impact of changing climate and oceanographic climatology; further research will use this long-term research to developed targeted sampling and experimental manipulations to better understand ecosystem structure and function

Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls