An analysis of perioperative factors that were independently associated with survival up to 1000 days after scheduled colorectal adenocarcinoma resections in 314 patients.
The association of 16 ...perioperative variables with postoperative survival and critical care unit (CCU) admission after scheduled resections for colorectal adenocarcinoma between September 2005 and March 2009 was analysed using multivariable Cox regression analyses and Fisher's exact tests.
We followed survivors for a mean of 983 days (range 696–1000 days). Average annual postoperative mortality was 8.5%, 14% after surgery performed in 2005, and 3% after surgery in 2009. Risk of mortality was independently associated with five variables after stratifying for date of surgery: attending a preoperative high-risk clinic hazard ratio (HR) 0.42, P=0.006, worse World Health Organization performance status (HR 2.1, P=0.001), BMI (HR 0.92, P=0.009), higher nodal stage (HR 2.6, P<0.0001), and unplanned critical care admission (HR 7.2, P<0.0001). Patients who attended the preoperative clinic (207) were older, with worse renal function and ASA grade, than those who did not (107). Planned postoperative critical care admission was more common in patients who attended the high-risk clinic (24% vs 12%, P=0.01) and may have partly accounted for the observed mortality difference.
Immediate perioperative care may have prolonged effects on postoperative survival. Specialized preoperative assessment clinics may reduce mortality after colorectal surgery.
Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, ...resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward.
Reliable, sensitive, and widely available hydrogen chloride (HCl)
measurements are important for understanding oxidation in many regions of
the troposphere. We configured a commercial HCl cavity ...ring-down
spectrometer (CRDS) for sampling HCl in the ambient atmosphere and developed
validation techniques to characterize the measurement uncertainties. The
CRDS makes fast, sensitive, and robust measurements of HCl in a high-finesse optical cavity coupled to a laser centred at 5739 cm−1. The accuracy was determined to reside between 5 %–10 %, calculated from laboratory and ambient air intercomparisons with annular denuders. The precision and limit of detection (3σ) in the 0.5 Hz measurement were below 6 and 18 pptv, respectively, for a 30 s integration interval in zero air. The
response time of this method is primarily characterized by fitting decay
curves to a double exponential equation and is impacted by inlet
adsorption/desorption, with these surface effects increasing with relative humidity and
decreasing with decreasing HCl mixing ratios. The minimum 90 % response
time was 10 s and the equilibrated response time for the tested inlet
was 2–6 min under the most and least optimal conditions, respectively.
An intercomparison with the EPA compendium method for quantification of
acidic atmospheric gases showed good agreement, yielding a linear
relationship statistically equivalent to unity (slope of
0.97 ± 0.15).
The CRDS from this study can detect HCl at atmospherically relevant mixing
ratios, often performing comparably or better in sensitivity, selectivity,
and response time than previously reported HCl detection methods.
•The 2018 AO/OTA classification has a “moderate” inter-observer reliability at group (e.g. 31-A1) level, this reduces to “fair” reliability at sub-group (e.g. 31-A1.1) with sub-group ...classifications.•Intra-observer reliability is comparably higher than inter-observer reliability being “substantial” to “moderate”.•Despite attempts to simplify and re-define inter-trochanteric fractures, the 2018 AO/OTA classification remains difficult to apply consistently and reliably.
Hip fractures are a global health burden, with an incidence that is projected to increase from 66,000/year currently in the United Kingdom to 100,000/year by 2033. The classification of intertrochanteric fractures is key to the treatment algorithms advising on their surgical management.
The AO/OTA classification is the most commonly used system, initially published in 1990 and subsequently shown to have poor inter- and intra-observer reliability, it was revised in 2018 with the main aim of re-classifying and further defining the 31-A2 group.
150 plain film anteroposterior and lateral plain film radiographs of intertrochanteric fractures from three hospitals were classified using the 2018 AO/OTA classification of intertrochanteric fractures by six Orthopaedic Surgeons (2 Consultants, 4 Trainees), all were blinded to the definitive surgical treatment for patients. Radiographs were re-classified after a minimum of 3-months, Cohen's Kappa for inter-observer reliability was calculated from first round classifications and intra-observer reliability from first and second classifications.
Mean Kappa for inter-observer reliability for AO group classification (e.g. 31-A1) was 0.479 (0.220 - 0.771, for sub-group classification (e.g. 31-A1.1) reliability reduced to 0.376 (0.276 - 0.613). Intra-observer reliability was comparable for both group and sub-group classifications, 0.661 and 0.587 respectively.
The revised 2018 AO/OTA classification aimed to simply the classification of intertrochanteric fractures, however it remains unreliable with only a “moderate” inter-observer reliability at group level with this falling to “fair” when sub-group classifications are made. Identification of stable and unstable injuries using the new AO/OTA system remains fraught with difficulties and appears difficult to apply with consistent accuracy.
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients ...treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB).
A retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan-Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy.
Forty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil.
In summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.
Research suggests that early parenting may contribute to the development of self-harm but this has not been examined longitudinally. In this study, we explored the relationship between early ...parenting and self-harm in adolescence and considered whether (1) emotion regulation and (2) decision-making in childhood mediate the relationship between early parenting and self-harm.
Using longitudinal data from the Millennium Cohort Study (MCS), we tested mediation models exploring the relationship between early parenting and self-harm in adolescence via emotion regulation and decision-making. Parenting was assessed at age 3 with measures of conflict, closeness and discipline. The trajectories of independence & self-regulation and emotional dysregulation were modelled from ages 3 to 7 years through latent growth curve analysis, with individual predicted slope and intercept values used in the mediation models. Decision-making (deliberation time, total time, delay aversion, quality of decision making, risk adjustment, risk-taking) was assessed using the Cambridge Gambling Task (CGT) at age 11.
In our sample (n = 11,145), we found no evidence of a direct association between early parenting and self-harm in adolescence. However, there were indirect effects of parenting (conflict and closeness) on self-harm via the slope of emotional dysregulation. Furthermore, delay aversion was positively associated with self-harm in adolescence.
It must be acknowledged that we cannot determine causality and that self-report measures of parenting are vulnerable to several biases.
The findings support early identification and interventions for children exhibiting chronic emotional dysregulation and decision-making characterised by a bias for smaller, immediate over larger, delayed rewards.
•Indirect effects of early parenting on adolescent self-harm via chronic emotional dysregulation in childhood.•Delay aversion in childhood is associated with self-harm in adolescence.•Findings support interventions for chronic emotional dysregulation and delay aversion in childhood.
Although therapy for limited-stage small-cell lung cancer (LS-SCLC) is administered with curative intent, most patients relapse and eventually die of recurrent disease. Chemotherapy (CT) with ...concurrent radiotherapy (RT) remains the standard of care for LS-SCLC; however, this could evolve in the near future. Therefore, understanding the current prognostic factors associated with survival is essential.
This real-world analysis examines factors associated with long-term survival in patients with LS-SCLC treated with CT in Manitoba, Canada.
A retrospective cohort study was conducted using Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years and had cytologically confirmed LS-SCLC diagnosed between January 1, 2004, and December 31, 2018, for which they received CT ± RT. Baseline patient, disease, and treatment characteristics and survival duration, characterized as short (<6 months), medium (6-24 months), and long term (>24 months), were extracted. Overall survival (OS) was estimated at one, two, and five years and assessed using Kaplan-Meier methods and Cox proportional hazards models.
Over the 15-year study period, 304 patients met the eligibility criteria. Long-term survivors comprised 39.1% of the cohort; at diagnosis, this subgroup was younger, more likely to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, and have normal lactate dehydrogenase, sodium, and hemoglobin levels. OS estimates for the entire cohort at one, two, and five years were 66%, 38%, and 18%, respectively. In the ECOG PS 0 subgroup, OS estimates at one, two, and five years were 85%, 52%, and 24%, respectively; OS estimates were 60%, 35%, and 17%, respectively, for ECOG PS 1-2 and were 47%, 23%, and 10%, respectively, for ECOG PS 3-4. OS was significantly higher among patients with normal serum sodium and hemoglobin levels than those with abnormal levels. Univariable hazard regression models found that ECOG PS, age at diagnosis, receipt of prophylactic cranial irradiation (PCI), and thoracic RT were associated with survival. On multivariable hazard regression, ECOG PS and receipt of PCI were associated with survival.
Survival for greater than two years in patients with LS-SCLC treated with CT ± RT was associated with ECOG PS and receipt of PCI.
Background
Extensive-stage small-cell lung cancer (ES-SCLC) is an incurable cancer with poor prognosis in which characteristics predictive of long-term survival are debated. The utility of agents ...such as immune checkpoint inhibitors highlights the importance of identifying key characteristics and treatment strategies that contribute to long-term survival and could help guide therapeutic decisions.
Objective
This real-world analysis examines the characteristics, treatment patterns, and clinical outcomes of patients receiving chemotherapy without immunotherapy for ES-SCLC in Manitoba, Canada.
Methods
A retrospective cohort study assessed patient characteristics, treatment, and survival duration (short: <6 months; medium: 6–24 months; long: >24 months) using the Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years with cytologically confirmed ES-SCLC diagnosed between January 1, 2004, and December 31, 2018, and received cytotoxic chemotherapy (CT). The one-, two-, and five-year probabilities of overall survival (OS) were assessed relative to patient, disease, and treatment characteristics using Kaplan-Meier methods and Cox proportional hazards models.
Results
This analysis included 537 patients. Cisplatin was used in 56.1% of patients, 45.6% received thoracic radiotherapy (RT), and few received prophylactic cranial irradiation (PCI). In the overall cohort, one-, two- and five-year OS rates were 26%, 8%, and 3%, respectively. For patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, OS rates at one, two, and five years were 43%, 17%, and 10%, respectively, vs. 27%, 8%, and 2% for those with ECOG PS 1–2, and 16%, 3%, and 3% for those with ECOG PS 3–4. In long-term survivors, ECOG PS scores were lower and abnormal laboratory test results were less frequent. Overall, 74.4% of long-term survivors received thoracic RT and 53.5% received PCI. Known poor prognostic factors – including brain/liver metastases, high lactate dehydrogenase (LDH), abnormal sodium, and low hemoglobin levels – were less common but still seen in long-term survivors.
Conclusion
Although rare, patients with ES-SCLC may experience long-term survival with CT ± thoracic RT ± PCI. Factors predicting long-term survival include traditional prognostic factors such as ECOG PS, LDH level, and receipt of thoracic RT or PCI. These findings support current treatment algorithms for ES-SCLC and provide baseline survival estimates to assess the real-world impact of adding immune checkpoint inhibitors in the future.
Most posterior hindfoot procedures have been described with the patient positioned prone. This affords excellent access to posterior hindfoot structures but has several disadvantages for the ...management of the airway, the requirement for an endotracheal tube in all patients, difficulty with ventilation and an increased risk of pressure injuries, especially with regard to reduced ocular perfusion. We describe use of the 'recovery position', which affords equivalent access to the posterior aspect of the ankle and hindfoot without the morbidity associated with the prone position. A laryngeal mask rather than endotracheal tube may be used in most patients. In this annotation we describe this technique, which offers a safe and simple alternative method of positioning patients for posterior hindfoot and ankle surgery.
FISH cytogenetics, TP53 sequencing, and IGHV mutational status are increasingly used as prognostic and predictive markers in chronic lymphocytic leukemia (CLL), particularly as components of the CLL ...International Prognostic Index (CLL-IPI) and in directing therapy with novel agents. However, testing outside of clinical trials is not routinely available in Canada. As a centralized CLL clinic at CancerCare Manitoba, we are the first Canadian province to evaluate clinical outcomes and survivorship over a long period of time, incorporating the impact of molecular testing and the CLL-IPI score. We performed a retrospective analysis on 1315 patients diagnosed between 1960 and 2018, followed over a 12-year period, where 411 patients had molecular testing and 233 patients had a known CLL-IPI score at the time of treatment. Overall, 40.3% (
= 530) of patients received treatment, and 47.5% (
= 252) of patients received multiple lines of therapy. High-risk FISH and CLL-IPI (4-10) were associated with higher mortality (HR 2.03,
= 0.001; HR 2.64,
= 0.002), consistent with other studies. Over time, there was an increase in the use of targeted agents in treated patients. The use of Bruton's tyrosine kinase inhibitors improved survival in patients with unmutated IGHV and/or TP53 aberrations (HR 2.20,
= 0.001). The major cause of death in patients who received treatment was treatment/disease-related (32%,
= 42) and secondary malignancies (57%,
= 53) in those who were treatment-naïve. Our data demonstrate the importance of molecular testing in determining survivorship in CLL and underpinning the likely immune differences in outcomes for those treated for CLL.
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