Study of the strongest dust storm occurred in Uzbekistan in November 2021.

We studied and reconstructed a severe Central Asian dust storm of November 4, 2021, through high-resolution TROPOMI UVAI spaceborne observations, ground-based aerosol measurements, and Lagrangian particle modeling. The dust storm was caused by the front part of a cold polar anticyclone front from the Ural-Volga regions, which struck the central and eastern parts of Uzbekistan under favorable atmospheric conditions. Two plumes spread out, causing a thick haze to blanket the region. The most severe dust storm effects hit the capital of Uzbekistan (Tashkent) and the Fergana Valley, where the thick atmospheric dust layer dropped the visibility to 200 m. PM10 concentrations reached 18,000 µg/m3 (260-fold exceedance of the local long-term average). The PM2.5 concentrations remained above 300 µg/m3 for nearly ten days, indicating an extremely long-lasting event. The dust storm was caused by an extremely strong summer heatwave of 2021 in Kazakhstan with unprecedentedly high temperatures reaching 46.5 °C. The long-lasting drought dried up the soil down to 50 cm depth, triggering the soil cover denudation due to drying out vegetation and losing its moisture. This event was the worst since 1871 and considering the increasing aridity of Central Asia, the onset of potentially recurring severe dust storms is alarming.

Medullary Tegmental Cap Dysplasia: Fetal and Postnatal Presentations of a Unique Brainstem Malformation.

BACKGROUND AND PURPOSE: Medullary tegmental cap dysplasia is a rare brainstem malformation, first described and defined by James Barkovich in his book Pediatric Neuroimaging from 2005 as an anomalous mass protruding from the posterior medullary surface. We describe the neuroimaging, clinical, postmortem, and genetic findings defining this unique malformation. MATERIALS AND METHODS: This is a multicenter, international, retrospective study. We assessed the patients' medical records, prenatal ultrasounds, MR images, genetic findings, and postmortem results. We reviewed the medical literature for all studies depicting medullary malformations and evaluated cases in which a dorsal medullary protuberance was described. RESULTS: We collected 13 patients: 3 fetuses and 10 children. The medullary caps had multiple characteristics. Associated brain findings were a rotated position of the medulla, a small and flat pons, cerebellar anomalies, a molar tooth sign, and agenesis of the corpus callosum. Systemic findings included the following: polydactyly, hallux valgus, large ears, and coarse facies. Postmortem analysis in 3 patients revealed that the cap contained either neurons or white matter tracts. We found 8 publications describing a dorsal medullary protuberance in 27 patients. The syndromic diagnosis was Joubert-Boltshauser syndrome in 11 and fibrodysplasia ossificans progressiva in 14 patients. CONCLUSIONS: This is the first study to describe a series of 13 patients with medullary tegmental cap dysplasia. The cap has different shapes: distinct in Joubert-Boltshauser syndrome and fibrodysplasia ossificans progressive. Due to the variations in the clinical, imaging, and postmortem findings, we conclude that there are multiple etiologies and pathophysiology. We suggest that in some patients, the pathophysiology might be abnormal axonal guidance.

"Virtual patch clamp analysis" for predicting the functional significance of pathogenic variants in sodium channels.

OBJECTIVE: Opening of voltage-gated sodium channels is crucial for neuronal depolarization. Proper channel opening and influx of Na+ through the ion pore, is dependent upon binding of Na+ ion to a specific amino-acid motif (DEKA) within the pore. In this study we used molecular dynamic simulations, an advanced bioinformatic tool, to research the dysfunction caused by pathogenic variants in SCN1a, SCN2a and SCN8a genes. METHOD: Molecular dynamic simulations were performed in six patients: three patients with Dravet syndrome (p.Gly177Ala,p.Ser259Arg and p.Met1267Ile, SCN1a), two patients with early onset drug resistant epilepsy(p.Ala263Val, SCN2a and p.Ile251Arg, SCN8a), and a patient with autism (p.Thr155Ala, SCN2a). After predicting the 3D-structure of mutated proteins by homology modeling, time dependent molecular dynamic simulations were performed, using the Schrödinger algorithm. The opening of the sodium channel, including the detachment of the sodium ion to the DEKA motif and pore diameter were assessed. Results were compared to the existent patch clamp analysis in four patients, and consistency with clinical phenotype was noted. RESULTS: The Na+ ion remained attached to DEKA filter longer when compared to wild type in the p.Gly177Ala, p.Ser259Arg,SCN1a, and p.Thr155Ala, SCN2a variants, consistent with loss-of-function. In contrast, it detached quicker from DEKA than wild type in the p.Ala263Val,SCN2a variant, consistent with gain-of-function. In the p.Met1267Ile,SCN1a variant, detachment from DEKA was quicker, but pore diameter decreased, suggesting partial loss-of-function. In the p.Leu251Arg,SCN8a variant, the pore remained opened longer when compared to wild type, consistent with a gain-of-function. The molecular dynamic simulation results were consistent with the existing patch-clamp analysis studies, as well as the clinical phenotype. SIGNIFICANCE: Molecular dynamic simulation can be useful in predicting pathogenicity of variants and the disease phenotype, and selecting targeted treatment based on channel dysfunction. Further development of these bioinformatic tools may lead to "virtual patch-clamp analysis".

Spaceborne NO2 observations are sensitive to coal mining and processing in the largest coal basin of Russia.

Coal use exacerbates several major environmental problems including build-up of greenhouse gases and air quality deterioration. Although Kuzbass (Siberia) is one of the largest exploited coal basins worldwide, the role of regional coal mining and processing in atmospheric pollution is unknown. We outlined the Kuzbass coal basin by spaceborne night-lights and revealed a regional, long-term tropospheric NO2 anomaly (2005-2018) by spaceborne NO2 column observations (hereafter ‒ NO2). The spatial agreement between NO2 and night-lights indicates that the anomaly is attributable to an agglomeration of coal quarries and the cities in Kuzbass, that are heavily reliant on coal. A positive relationship between NO2 and interannual coal production suggested that the anomaly was related to coal in Kuzbass; ~ 1.0% of annual coal production increase induced ~ 0.5-0.6% of NO2 enhancement. As coal production accelerated since 2010, NO2 exhibited strikingly similar annual increases over Kuzbass in 2010-2014 (7%) and 2015-2019 (15%), compared to 2005-2009. Conversely, Siberian cities lacking a coal industry followed the global trend of reducing NO2 for the same periods (-5% and -14%, respectively), driven by fuel combustion improvements. Overall, we demonstrated that coal mining, processing and utilization can induce distinct tropospheric NO2 anomalies, detectable from space.

PATCH-DP: a single-arm phase II trial of intra-operative application of HEMOPATCH™ to the pancreatic stump to prevent post-operative pancreatic fistula following distal pancreatectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is the most significant cause of morbidity following distal pancreatectomy. Hemopatch™ is a thin, bovine collagen-based hemostatic sealant. We hypothesized that application of Hemopatch™ to the pancreatic stump following distal pancreatectomy would decrease the incidence of clinically-significant POPF. METHODS: We conducted a prospective, single-arm, multicentre phase II study of application of Hemopatch™ to the pancreatic stump following distal pancreatectomy. The primary outcome was clinically-significant POPF within 90 days of surgery. A sample size of 52 patients was required to demonstrate a 50% relative reduction in Grade B/C POPF from a baseline incidence of 20%, with a type I error of 0.2 and power of 0.75. Secondary outcomes included incidence of POPF (all grades), 90-day mortality, 90-day morbidity, re-interventions, and length of stay. RESULTS: Adequate fixation Hemopatch™ to the pancreatic stump was successful in all cases. The rate of grade B/C POPF was 25% (95%CI: 14.0-39.0%). There was no significant difference in the incidence of grade B/C POPF compared to the historical baseline (p = 0.46). The 90-day incidence of Clavien-Dindo grade ≥3 complications was 26.9% (95%CI: 15.6-41.0%). CONCLUSION: The use of Hemopatch™ was not associated with a decreased incidence of clinically-significant POPF compared to historical rates. (NCT03410914).

Prenatal diagnosis of rhombencephalosynapsis: neuroimaging features and severity of vermian anomaly.

OBJECTIVES: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly. METHODS: In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES. RESULTS: Included in the study were 62 fetuses with a gestational age ranging between 12 and 37 weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) < 3rd centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption. CONCLUSIONS: This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Patient-reported symptoms in metastatic gastric cancer patients in the last 6 months of life.

BACKGROUND: Patients with metastatic gastric cancer have poor survival outcomes and may experience high symptom burden. We evaluated symptom trajectory and risk factors for increased symptom severity among metastatic gastric cancer patients during the last 6 months of life. METHODS: We conducted a retrospective cohort study among patients ≥ 18 years diagnosed with metastatic gastric cancer from January 2007 to December 2014 in the province of Ontario, Canada. We included patients who died during the study period and who reported at least one Edmonton Symptom Assessment System (ESAS) score during the last 6 months of life. We described the proportion of patients who reported moderate-to-severe symptom scores (≥ 4) by month. Multivariable logistic regression models were created to identify risk factors for moderate-to-severe symptom scores. RESULTS: Seven hundred eighty-eight eligible patients with 3286 unique symptom scores completed during their last 6 months of life were identified. The highest prevalence of moderate-to-severe scores was observed for tiredness and lack of appetite, while nausea and depression had the lowest prevalence of elevated scores. The prevalence of moderate-to-severe was consistently high for all symptoms, particularly approaching end-of-life. Timing of ESAS scores, receipt of cancer-directed therapy, urban residence, and female sex were associated with increased odds of reporting moderate-to-severe symptom scores. CONCLUSION: Patients with metastatic gastric cancer experience significant symptom burden at the end-of-life. Routine screening with patient-reported outcome tools may assist in shared decision-making and effective palliative care by ensuring patients' health status and supportive care needs are identified promptly at the time of clinical encounters.

Association Between Preoperative Patient-Reported Symptoms and Postoperative Outcomes in Rectal Cancer Patients: A Retrospective Cohort Study.

BACKGROUND: Rectal cancer patients undergoing preoperative radiotherapy experience a significant symptom burden. However, it is unknown whether symptoms during radiotherapy may portend adverse postoperative outcomes and healthcare utilization. METHODS: A retrospective cohort study was performed of rectal cancer patients undergoing neoadjuvant radiotherapy and proctectomy in Ontario from 2007 to 2014. The primary outcome was a complicated postoperative course-a dichotomous variable created as a composite of postoperative mortality, major morbidity, or hospital readmission. Patient-reported Edmonton Symptom Assessment System (ESAS) scores, collected routinely at outpatient provincial cancer center visits, were linked to administrative healthcare databases. The receiver-operating characteristic analysis was used to compare ESAS scoring approaches and to stratify patients into low versus high symptom score groups. Multivariable regression models were constructed to evaluate associations between preoperative symptom scores and postoperative outcomes. RESULTS: 1455 rectal cancer patients underwent sequential radiotherapy and proctectomy during the study period and recorded symptom assessments. Patients with high preoperative symptom scores were significantly more likely to experience a complicated postoperative course (OR 1.55, 95% CI 1.23-1.95). High preoperative ESAS scores were also associated with the secondary outcomes of emergency department visits (OR 1.34, 95% CI 1.08-1.66) and longer length of stay (IRR 1.23, 95% CI 1.04-1.45). CONCLUSIONS: Rectal cancer patients reporting elevated symptom scores during neoadjuvant radiotherapy have increased odds of experiencing a complicated postoperative course. Preoperative patient-reported outcome screening may be a useful tool to identify at-risk patients and to efficiently direct perioperative supportive care.

Molecular Dialogues between Early Divergent Fungi and Bacteria in an Antagonism versus a Mutualism.

Fungal-bacterial symbioses range from antagonisms to mutualisms and remain one of the least understood interdomain interactions despite their ubiquity as well as ecological and medical importance. To build a predictive conceptual framework for understanding interactions between fungi and bacteria in different types of symbioses, we surveyed fungal and bacterial transcriptional responses in the mutualism between Rhizopus microsporus (Rm) (ATCC 52813, host) and its Mycetohabitans (formerly Burkholderia) endobacteria versus the antagonism between a nonhost Rm (ATCC 11559) and Mycetohabitans isolated from the host, at two time points, before and after partner physical contact. We found that bacteria and fungi sensed each other before contact and altered gene expression patterns accordingly. Mycetohabitans did not discriminate between the host and nonhost and engaged a common set of genes encoding known as well as novel symbiosis factors. In contrast, responses of the host versus nonhost to endobacteria were dramatically different, converging on the altered expression of genes involved in cell wall biosynthesis and reactive oxygen species (ROS) metabolism. On the basis of the observed patterns, we formulated a set of hypotheses describing fungal-bacterial interactions and tested some of them. By conducting ROS measurements, we confirmed that nonhost fungi increased production of ROS in response to endobacteria, whereas host fungi quenched their ROS output, suggesting that ROS metabolism contributes to the nonhost resistance to bacterial infection and the host ability to form a mutualism. Overall, our study offers a testable framework of predictions describing interactions of early divergent Mucoromycotina fungi with bacteria.IMPORTANCE Animals and plants interact with microbes by engaging specific surveillance systems, regulatory networks, and response modules that allow for accommodation of mutualists and defense against antagonists. Antimicrobial defense responses are mediated in both animals and plants by innate immunity systems that owe their functional similarities to convergent evolution. Like animals and plants, fungi interact with bacteria. However, the principles governing these relations are only now being discovered. In a study system of host and nonhost fungi interacting with a bacterium isolated from the host, we found that bacteria used a common gene repertoire to engage both partners. In contrast, fungal responses to bacteria differed dramatically between the host and nonhost. These findings suggest that as in animals and plants, the genetic makeup of the fungus determines whether bacterial partners are perceived as mutualists or antagonists and what specific regulatory networks and response modules are initiated during each encounter.

Symptom Burden of Nonresected Pancreatic Adenocarcinoma: An Analysis of 10,753 Patient-Reported Outcome Assessments.

OBJECTIVES: Pancreatic adenocarcinoma (PAC) is a debilitating disease. We sought to analyze symptom burden and trajectories after diagnosis of PAC and identify predictors of severe symptoms for nonresected patients. METHODS: This was a retrospective review of linked administrative health care databases examining patients with PAC not undergoing resection. Primary outcome was severe patient-reported symptoms (Edmonton Symptom Assessment System ≥7). Multivariable modified Poisson regression models were used to identify factors associated with reporting severe symptoms. RESULTS: A total of 10,753 symptom assessments from 2168 patients were analyzed. The median age was 67 years, and 47% were female; median survival was 7 months. Most common severe symptoms were tiredness (54.7%), anorexia (53.6%), overall impaired well-being (45.3%), and drowsiness (37.1%). Severity of symptoms decreased 1 month after diagnosis and plateaued 4 months after diagnosis. Female sex, comorbidities, and older age were associated with reporting severe symptoms; recent radiation treatment and residence in a rural community were associated with reporting less severe symptoms. CONCLUSIONS: The prevalence of severe symptoms in patients with nonresected PAC was high, but potentially modifiable. We identified vulnerable groups of patients that may benefit from focused interventions. This information is important for patient counseling and design of supportive care strategies.

Patient-Reported Symptom Severity Among 22,650 Cancer Outpatients in the Last Six Months of Life.

CONTEXT: Understanding the magnitude and risk factors for symptom burden of patients with cancer at the end of life is critical to guiding effective patient- and system-level interventions. OBJECTIVES: We aimed to estimate the prevalence of severe patient-reported symptoms among cancer outpatients during the six months before death and to identify patient groups at a higher risk for reporting severe symptoms. METHODS: This was a retrospective cohort study of cancer decedents at regional cancer centers from 2010 to 2016. Patient-reported Edmonton Symptom Assessment System (ESAS) scores from the last six months of life were linked to administrative databases. The proportion of patients reporting severe symptom scores (≥7) for anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and overall well-being during the six months before death was described. Multivariable modified Poisson regression analyses were used to identify risk factors for reporting severe symptom scores. RESULTS: Of 39,084 cancer decedents, 22,650 had one or more symptom assessments recorded in the last six months of life, resulting in 92,757 ESAS assessments. Severe scores were highest for tiredness (56%), lack of appetite (46%), and impaired well-being (45%). The proportion of patients reporting severe symptom scores was stable before progressively increasing at three months before death. Elderly, women, patients with high comorbidity, immigrants, and living in urban areas or with high material deprivation were at increased risk of reporting severe scores. CONCLUSIONS: Despite an integrated symptom screening program, rates of severe patient-reported symptom scores before death were high for outpatients with cancer. Patient subgroups at increased risk of severe symptom burden may benefit from targeted interventions. Ongoing review of routinely collected symptom data may be used to assess the supportive care needs and guide targeted interventions at the health-system level.

Molecular dynamics complemented by site-directed mutagenesis reveals significant difference between the interdomain salt bridge networks stabilizing oligopeptidases B from bacteria and protozoa in their active conformations.

Oligopeptidases B (OpdBs) are trypsin-like peptidases from protozoa and bacteria that belong to the prolyl oligopeptidase (POP) family. All POPs consist of C-terminal catalytic domain and N-terminal ß-propeller domain and exist in two major conformations: closed (active), where the domains and residues of the catalytic triad are positioned close to each other, and open (non-active), where two domains and residues of the catalytic triad are separated. The interdomain interface, particularly, one of its salt bridges (SB1), plays a role in the transition between these two conformations. However, due to double amino acid substitution (E/R and R/Q), this functionally important SB1 is absent in γ-proteobacterial OpdBs including peptidase from Serratia proteamaculans (PSP). In this study, molecular dynamics was used to analyze inter- and intradomain interactions stabilizing PSP in the closed conformation, in which catalytic H652 is located close to other residues of the catalytic triad. The 3D models of either wild-type PSP or of mutant PSPs carrying activating mutations E125A and D649A in complexes with peptide-substrates were subjected to the analysis. The mechanism that regulates transition of H652 from active to non-active conformation upon domain separation in PSP and other γ-proteobacterial OpdB was proposed. The complex network of polar interactions within H652-loop/C-terminal α-helix and between these areas and ß-propeller domain, established in silico, was in a good agreement with both previously published results on the effects of single-residue mutations and new data on the effects of the activating mutations on each other and on the low active mutant PSP-K655A.Communicated by Ramaswamy H. Sarma.

Computer simulations of colloidal gels: how hindered particle rotation affects structure and rheology.

The effects of particle roughness and short-ranged non-central forces on colloidal gels are studied using computer simulations in which particles experience a sinusoidal variation in energy as they rotate. The number of minima n and energy scale K are the key parameters; for large K and n, particle rotation is strongly hindered, but for small K and n particle rotation is nearly free. A series of systems are simulated and characterized using fractal dimensions, structure factors, coordination number distributions, bond-angle distributions and linear rheology. When particles rotate easily, clusters restructure to favor dense packings. This leads to longer gelation times and gels with strand-like morphology. The elastic moduli of such gels scale as G'∝ω0.5 at high shear frequencies ω. In contrast, hindered particle rotation inhibits restructuring and leads to rapid gelation and diffuse morphology. Such gels are stiffer, with G'∝ω0.35. The viscous moduli G'' in the low-barrier and high-barrier regimes scale according to exponents 0.53 and 0.5, respectively. The crossover frequency between elastic and viscous behaviors generally increases with the barrier to rotation. These findings agree qualitatively with some recent experiments on heterogeneously-surface particles and with studies of DLCA-type gels and gels of smooth spheres.

Comparison of Patient-Reported Outcomes in Laparoscopic and Open Right Hemicolectomy: A Retrospective Cohort Study.

BACKGROUND: Open and laparoscopic resections for colon cancer have equivalent perioperative morbidity and mortality. However, there are little data concerning patient-reported outcomes in the early postdischarge period. OBJECTIVE: We examined patient-reported outcomes in the early postdischarge period for open and laparoscopic right hemicolectomy for colon cancer. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted using linked administrative healthcare databases in the province of Ontario, Canada. PATIENTS: Patients undergoing laparoscopic or open right hemicolectomy for colon cancer between January 2010 and December 2014 were identified using the Ontario Cancer Registry and physician billing data. MAIN OUTCOME MEASURES: The primary outcome was the presence of moderate-to-severe symptom scores on the Edmonton Symptom Assessment System (≥4 of 10) within 6 weeks of hospital discharge after right hemicolectomy. RESULTS: A total of 1022 patients completed ≥1 Edmonton Symptom Assessment System survey within 6 weeks of surgery and were included in the study. Patients undergoing laparoscopic resection were more likely to have an urban residence, to have undergone planned resections, and to have had proportionally more stage 1 disease compared with patients undergoing open resection. On multivariable analyses, adjusting for patient demographics, cancer stage, and planned versus unplanned admission status, there were no differences in the adjusted odds of moderate-to-severe symptom scores between the laparoscopic and open approaches. LIMITATIONS: Edmonton Symptom Assessment System scores are not collected for inpatients and thus only represent outpatient postoperative visits. Scores were reported by 19% of all resections in the population, with a bias to patients treated at cancer centers, and therefore they are not fully representative of the general population of right hemicolectomy. The Edmonton Symptom Assessment System is not a disease-specific tool and may not measure all relevant outcomes for patients undergoing right hemicolectomy. CONCLUSIONS: Receipt of the open or laparoscopic surgical technique was not associated with increased risk of elevated symptom burden in the early postdischarge period. See Video Abstract at http://links.lww.com/DCR/B27. REPORTE COMPARATIVO DE RESULTADOS INFORMADOS DE PACIENTES CON HEMICOLECTOMÍA DERECHA LAPAROSCÓPICA Y ABIERTA: UN ESTUDIO DE COHORTE RETROSPECTIVO: Las resecciones abiertas y laparoscópicas para el cáncer de colon, presentan semejante morbilidad y mortalidad perioperatoria. Sin embargo, en el período inicial posterior al alta, hay pocos datos sobre los resultados informados por los pacientes.Examinamos los resultados informados por los pacientes, en el período temprano posterior al alta, para hemicolectomía derecha abierta y laparoscópica en cáncer de colon.Estudio de cohorte retrospectivo.El estudio se realizó utilizando bases de datos administrativas de atención médica en la provincia de Ontario, Canadá.Pacientes sometidos a hemicolectomía derecha abierta o laparoscópica para cáncer de colon, de enero 2010 a diciembre 2014, se identificaron mediante el Registro de cáncer de Ontario y de los datos médicos de facturación.El resultado primario, después de la hemicolectomía derecha, fue la presencia de síntomas de moderados a graves en el Sistema de evaluación de síntomas de Edmonton (≥4 de cada 10) dentro de las seis semanas posteriores al alta hospitalaria.Un total de 1022 pacientes completaron al menos una encuesta del Sistema de evaluación de síntomas de Edmonton, dentro de las seis semanas de la cirugía y se incluyeron en el estudio. Los pacientes sometidos a resección laparoscópica fueron más propensos a residir en zona urbana, a resecciones planificadas y proporcionalmente más enfermedad en estadio 1; en comparación con los pacientes sometidos a resecciones abiertas. En los análisis multivariables, que se ajustaron a la demografía del paciente, al estadio del cáncer y del estado de ingreso planificado versus no planificado, no hubo diferencias en las probabilidades ajustadas de las puntuaciones de los síntomas moderados a severos entre el abordaje abierto o laparoscópico.Las puntuaciones del Sistema de evaluación de síntomas de Edmonton no se recopilan para pacientes hospitalizados y por lo tanto, solo representan las visitas postoperatorias de pacientes ambulatorios. Las puntuaciones informadas fueron del 19% de todas las resecciones en la población, con un sesgo en los pacientes tratados en los Centros de Cáncer y por lo tanto, no son totalmente representativos de la población general de hemicolectomía derecha. El Sistema de evaluación de síntomas de Edmonton no es una herramienta específica de la enfermedad y puede no medir todos los resultados relevantes para los pacientes que se someten a una hemicolectomía derecha.La recepción entre una técnica quirúrgica abierta o laparoscópica, no se asoció con un aumento del riesgo de síntomas en el período temprano posterior al alta. Vea el Resumen del Video en http://links.lww.com/DCR/B27.

Symptom burden among head and neck cancer patients in the first year after diagnosis: Association with primary treatment modality.

PURPOSE: Head and neck cancer (HNC) and its treatment affects quality of life, with significant symptom burden. The main objectives of this study were to examine symptom trajectories of HNC patients by treatment and to identify factors associated with high ESAS scores. METHODS AND MATERIALS: We conducted a retrospective cohort study in patients diagnosed with HNC in Ontario, Canada from 2007 to 2015 using linked health administrative databases. The primary outcome was a monthly patient self-reported moderate-to-severe (≥4) symptom score in the year following diagnosis. Multivariable Modified Poisson regression analyses with robust variance were used to investigate factors associated with moderate-to-severe scores. RESULTS: Of 13,827 HNC patients identified, 4793 had ≥1 ESAS assessment within 12 months of cancer diagnosis. Overall, 60% (n = 2708) and 65% (n = 2903) of patients reported moderate-to-severe pain and poor appetite, respectively. The proportion of patients reporting a score ≥4 increased significantly during treatment and was most pronounced for those who received chemoradiation (CRT). On multivariable analysis, patients who were female (Relative Risk (RR) 1.15, 95% CI 1.08-1.23, received CRT, had a higher comorbidity burden (RR 1.31, 1.23-1.39), and had a diagnosis of oropharyngeal (1.10, 1.02-1.19), or oral cavity cancer (1.31, 1.19-1.45), were at an increased risk of reporting severe pain scores (p < 0.01 for all). CONCLUSION: The majority of HNC patients report high pain scores, with symptom burden highest during the treatment phase, and especially for patients who received radiation or chemoradiation. This large study highlights the need for proactive symptom management during the HNC patients' cancer journey.

Economic Analysis of Adjuvant Chemoradiotherapy Compared with Chemotherapy in Resected Pancreas Cancer.

BACKGROUND: Population-based survival and costs of pancreas adenocarcinoma patients receiving adjuvant chemoradiation and chemotherapy following pancreaticoduodenectomy are poorly understood. METHODS: This retrospective cohort study used linked administrative and pathological datasets to identify all patients diagnosed with pancreas adenocarcinoma and undergoing pancreaticoduodenectomy in Ontario between April 2004 and March 2014, who received postoperative chemoradiation or chemotherapy. Stage and margin status were defined by using pathology reports. Kaplan-Meier and Cox proportional hazards regression survival analyses were used to determine associations between adjuvant treatment approach and survival, while stratifying by margin status. Median overall health system costs were calculated at 1 and 3 years for chemoradiation and chemotherapy, and differences were tested using the Kruskal-Wallis test. RESULTS: Among 709 patients undergoing pancreaticoduodenectomy for pancreas cancer during the study period, the median survival was 21 months. Median survival was 19 months for chemoradiation and 22 months for chemotherapy. Patients receiving chemoradiation were more likely to have positive margins: 47.7% compared with 19.2% in chemotherapy. After stratifying by margin status and controlling for confounders, adjusted hazard ratio of death were not statistically different between chemotherapy and chemoradiation [margin positive, hazard ratio (HR) = 0.99, 95% confidence interval (CI) = 0.88-1.27; margin negative, HR 0.95, 95% CI 0.91-1.18]. Overall 1-year health system costs were significantly higher for chemoradiation (USD $70,047) than chemotherapy (USD $54,005) (p ≤ 0.001). CONCLUSIONS: Chemotherapy and chemoradiation yielded similar survival, but chemoradiation resulted in higher costs. To create more sustainable healthcare systems, both the efficacy and costs of therapies should be considered.

Population-Level Symptom Assessment Following Pancreaticoduodenectomy for Adenocarcinoma.

Importance: Postoperative morbidity associated with pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA) remains as high as 70%. However, to our knowledge, few studies have examined quality of life in this patient population. Objective: To identify symptom burden and trajectories and factors associated with high symptom burden following PD for PA. Design, Setting, and Participants: This population-based cohort study of patients undergoing PD for PA diagnosed between 2009 and 2015 linked population-level administrative health care data to routinely prospectively collected Edmonton Symptom Assessment System (ESAS) scores from 2009 to 2015, with a data analysis undertaken in 2018. Exposures: Baseline characteristics, including age, sex, income quintile, rurality, immigration status, and comorbidity burden, as well as treatment characteristics, including year of surgery and receipt of chemotherapy. Main Outcome and Measures: The outcome of interest was moderate to severe symptoms (defined as ESAS ≥4) for anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and impaired well-being. The monthly prevalence of moderate to severe symptoms was presented graphically for each symptom. Multivariable regression models identified factors associated with the reporting of moderate to severe symptoms. Results: We analyzed 6058 individual symptom assessments among 615 patients with PA who underwent resection (285 women [46.3%]) with ESAS data. Tiredness (443 [72%]), impaired well-being (418 [68%]), and lack of appetite (400 [65%]) were most commonly reported as moderate to severe. The proportion of patients with moderate to severe symptoms was highest immediately after surgery (range, 14%-66% per symptom) and decreased over time, stabilizing around 3 months (range, 8%-42% per symptom). Female sex, higher comorbidity, and lower income were associated with a higher risk of reporting moderate to severe symptoms. Receipt of adjuvant chemotherapy was not associated with the risk of moderate to severe symptoms. Conclusions and Relevance: There is a high prevalence of symptoms following PD for PA, with improvement over the first 3 months following surgery. In what to our knowledge is the largest cohort reporting on symptom burden for this population, we have identified factors associated with symptom severity. These findings will aid in managing patients' perioperative expectations and designing strategies to improve targeted symptom management.

Symptom trajectories and predictors of severe symptoms in pancreatic adenocarcinoma at the end-of-life: a population based analysis of 2,538 patients.

BACKGROUND: We evaluated symptom trajectories and predictors of reporting severe symptoms in the last 6 months of life among non-resected pancreatic adenocarcinoma (PAC) decedents. METHODS: A retrospective cohort study of non-resected PAC decedents receiving care at regional cancer centres between January 2007 and December 2015. Symptoms were measured using the Edmonton Symptom Assessment System (ESAS). We described the proportion of patients reporting severe (score ≥7) symptoms by 2-week intervals during the six months prior to death. Multivariable modified Poisson regression models identified predictors of reporting severe symptom scores in the last 6 months of life. RESULTS: 2538 non-resected PAC decedents treated at regional cancer centres had ≥1 symptom ESAS record in the last six months of life, totaling 10,893 unique symptom assessments. Tiredness was the most commonly reported symptom (59% reporting ≥1 severe score), followed by lack of appetite (57%), impaired-wellbeing (49%) and drowsiness (42%). All symptoms increased closer to death. Older age, female sex, higher comorbidity status, survival less than 6 months, and urban residence were associated with a significantly higher risk of reporting severe symptoms. CONCLUSION: Non-resected PAC patients experience significant symptom burden nearing death. Patient subsets may benefit from personalized supportive care interventions.

Patterns of Symptoms Burden in Neuroendocrine Tumors: A Population-Based Analysis of Prospective Patient-Reported Outcomes.

BACKGROUND: How to best support patients with neuroendocrine tumors (NETs) remains unclear. Improving quality of care requires an understanding of symptom trajectories. Objective validated assessments of symptoms burden over the course of disease are lacking. This study examined patterns and risk factors of symptom burden in NETs, using patient-reported outcomes. SUBJECTS, MATERIALS, AND METHODS: A retrospective, population-based, observational cohort study of patients with NETs diagnosed from 2004 to 2015, who survived at least 1 year, was conducted. Prospectively collected patient-reported Edmonton Symptom Assessment System scores were linked to provincial administrative health data sets. Moderate-to-severe symptom scores were presented graphically for both the 1st year and 5 years following diagnosis. Multivariable Poisson regression identified factors associated with record of moderate-to-severe symptom scores during the 1st year after diagnosis. RESULTS: Among 2,721 included patients, 7,719 symptom assessments were recorded over 5 years following diagnosis. Moderate-to-severe scores were most frequent for tiredness (40%-51%), well-being (37%-49%), and anxiety (30%-40%). The proportion of moderate-to-severe symptoms was stable over time. Proportion of moderate-to-severe anxiety decreased by 10% within 6 months of diagnosis, followed by stability thereafter. Changes were below 5% for other symptoms. Similar patterns were observed for the 1st year after diagnosis. Primary tumor site, metastatic disease, younger age, higher comorbidity burden, lower socioeconomic status, and receipt of therapy within 30 days of assessment were independently associated with higher risk of elevated symptom burden. CONCLUSION: Patients with NETs have a high prevalence of moderate-to-severe patient-reported symptoms, with little change over time. Patients remain at risk of prolonged symptom burden following diagnosis, highlighting potential unmet needs. Combined with identified patient and disease factors associated with moderate-to-severe symptom scores, this information is important to support symptom management strategies to improve patient-centered care. IMPLICATIONS FOR PRACTICE: This study used population-level, prospectively collected, validated, patient-reported outcome measures to appraise the symptoms burden and trajectory of patients with neuroendocrine tumors (NETs) after diagnosis. It is the largest and most detailed analysis of patient-reported symptoms for NETs. Patients with NETs present a high burden of symptoms at diagnosis that persists up to 5 years later, highlighting unmet needs. Early and comprehensive symptom screening and management programs are needed. This information should serve to devise pathways and policies to better support patients, evaluate supportive interventions, and assess the effectiveness of symptom management at the provider, institutional, and system levels.