sEMG Biofeedback for Episodic Migraines: A Pilot Randomized Clinical Trial.

The aim of this study was to assess the feasibility and potential effectiveness of a 6-week virtual sEMG biofeedback intervention for patients with episodic migraines. Patients with episodic migraines were randomized to treatment with a novel surface EMG (sEMG) at-home biofeedback device or a treatment as usual control group; they completed validated baseline and post-intervention assessments of migraine related disability (migraine-specific quality of life, anxiety and depression). Participants also underwent a series of Quantitative Sensory Testing (QST) procedures referring to several different tests that quantitatively assess responses to mechanical stimuli during two separate visits (baseline and post intervention). No adverse events were reported during the study. Compared to the treatment as usual comparison group, patients in the sEMG biofeedback group reported lower migraine disability (p < 0.05). Compared to baseline, participants in the sEMG biofeedback group demonstrated statistically significant reductions in anxiety (p < 0.01), and significant increases in quality of life (p < 0.001), and significant decreases in temporal summation (p < 0.05) assessed by QST. No significant changes were observed in any of the outcomes in the control comparison group (p > 0.05). No significant changes were observed in migraine frequency in either of the two groups (p > 0.05). In addition, mediation analyses revealed that changes in migraine related quality of life mediated group effects on changes in migraine disability. Virtual sEMG biofeedback shows promise as a potential therapy for reducing disability, anxiety and depression and improving quality of life in individuals with episodic migraines. These results demonstrate the feasibility of a digital intervention for migraines and set the basis for conducting a future, larger scale randomized controlled trial to confirm these preliminary findings.

Systematic Review of the Clinical Characteristics and Management of Isaac Syndrome.

OBJECTIVES: Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle twitching, stiffness, hypertrophy, and dysautonomic characteristics, such as hyperhidrosis, are common manifestations. The syndrome can be autoimmune or paraneoplastic, with thymoma being a common cause of paraneoplastic IS. Furthermore, this condition could be handed down from one generation to another. However, there is limited information regarding outcomes, relapses, associated syndromes, associated malignancies (other than thymoma), and treatment options. Despite its rarity, there remains a need for effective management strategies for patients with IS. To address this gap, we conducted a systematic review to summarize the most common and effective treatments of IS in immunomodulatory agents and symptomatic medications, as well as to describe outcomes, relapses, and associated malignancies. Altogether, this review serves to guide clinical practice recommendations for IS and highlight areas for further research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to conduct a systematic review of cases reposted through the PubMed and Google Scholar databases. The terms "Isaac Syndrome" and "Acquired Neuromyotonia" were used. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the quality of the included studies. RESULTS: We identified 61 case reports and 4 case series, comprising a total of 70 patients with IS (mean age at onset: 42.5 ± 18 years, and 69% were males). Fourteen cases reported relapses. Thymoma was the most common malignancy associated with IS, followed by lymphoma. Among various serum antibodies, voltage-gated potassium channel-complex antibodies were the most reported antibodies elevated in IS (reported in 38 patients and elevated in 21 patients [55.2%]), followed by acetylcholine ganglionic receptor antibodies, which were reported in 30% of patients (n = 21) and were elevated in 5 cases. The most common electromyography findings were myokymic discharges (n = 22), followed by fasciculations (n = 21) and neuromyotonia (n = 19). For treatment, combining anticonvulsants such as carbamazepine with immunotherapy therapy showed the best results in controlling the symptoms. Among immunotherapy therapies, the combination of plasma exchange plus intravenous high-dose steroids achieved the best results in the acute treatment of IS ([n = 6], with improvement noted in 83.3% [n = 5] of cases). Among the symptomatic treatments with anticonvulsants, carbamazepine was the most efficacious anticonvulsant in treatment of IS, with an average effective dosing of 480 mg/day (carbamazepine was used in 32.3% of acute treatment strategies [n = 23], with improvement noted in 73.9% [n = 17] of cases). CONCLUSIONS: IS a rare neuromuscular syndrome that tends to affect middle-aged men. These patients should be screened for thymoma and other malignancies such as lymphomas. The management of IS symptoms can be challenging, but based on our review, the combination of multiple immunosuppressives such as IV steroids and plasmapheresis with anticonvulsants such as carbamazepine seems to achieve the best results.

The utility of H2 receptor antagonists in preventing infusion-related reactions to paclitaxel chemotherapy.

BACKGROUND: Paclitaxel has a risk of infusion-related reactions (IRRs) and despite no prospective evidence, is often given with premedication including a corticosteroid, H1 antagonist, and H2 antagonist (H2RA). Backorders impacted the supply of intravenous H2RAs at our center, and it was removed as routine premedication. The authors compared the incidence of IRR in patients treated without H2RA to patients receiving standard H2RA premedication. METHODS: The authors reviewed outpatients starting paclitaxel at the Ottawa Hospital from December 2019 to October 2021. Two cohorts were created: patients treated without H2RA premedication (intervention), and those receiving standard H2RA (control). Demographics, treatment, and IRR information were collected retrospectively. Primary end point was rate of grade ≥2 IRRs during first two doses of paclitaxel. RESULTS: A total of 182 patients were treated without H2RA premedication, compared to 184 control patients treated during non-backorder periods. Baseline characteristics included: median age, 63 years; 86% female; and primary tumor 52% breast/24% gynecologic/10% gastric/esophageal/8% lung/6% other. There were no significant differences between cohorts in baseline characteristics. There was no difference in the rate of grade ≥2 IRR between cohorts; 12.1% (22 of 182; 95% confidence interval [CI], 7.7%-17.7%) for patients treated without H2RA, and 15.1% (28 of 185; 95% CI, 10.3%-21.1%) for control patients. The rate of grade ≥3 IRRs were also similar, 4.4% in intervention cohort versus 3.8% in control cohort. CONCLUSIONS: The removal of H2RAs from premedication for paclitaxel did not result in an increased incidence of IRRs. The use of H2RAs in preventing IRRs to paclitaxel should be re-evaluated.

Medical Assistance in Dying in Patients With Cancer.

PURPOSE: Medical assistance in dying (MAiD) was legalized in Canada in 2016. To date, patients with cancer account for 69% of MAiD deaths, yet little information is available about these patients. We reviewed disease and treatment characteristics of patients with cancer who underwent MAiD to better understand this population and identify gaps in our current system of care. MATERIALS AND METHODS: Patients with cancer who underwent MAiD through the Champlain Regional MAiD Network from June 2016 to November 2020 were reviewed. Baseline demographic, diagnostic, and treatment details were collected by retrospective review. RESULTS: During the study period, 255 patients with cancer underwent MAiD. At the time of MAiD, 201 patients (79%) had metastatic disease. Most prevalent solid organ tumors were gastrointestinal (30%), lung (18%) and genitourinary (14%). MAiD was primarily provided in the home (48%) or an acute inpatient facility (40%). One hundred eighty-nine (74%) patients were evaluated by medical oncology, 23 by gynecology oncology (9%), 11 by hematology oncology (4%), and 177 (69%) by radiation oncology. One hundred fifty-eight (62%) patients were not seen by oncology specialists in the 30 days prior to MAiD. One hundred fifty-nine patients (62%) had at least one line of systemic therapy, 138 patients (54%) received radiotherapy, and 61 patients (24%) did not receive cancer-directed treatment. Palliative care assessed at least 213 patients (84%). Common reasons for pursuing MaiD included disease-related symptoms (33%), fear of future suffering or disability (19%), and the ability to control the time and manner of death (17%). In 36% of cases, the reason was not documented. CONCLUSION: Although formal oncology consultation is not required before MAiD, with an ever-increasing number of novel cancer therapies, oncologists, cancer centers, and MAiD providers should consider collaborating to ensure a streamlined assessment process for patients.

Management of Very Early Small Cell Lung Cancer: A Canadian Survey Study.

Concurrent chemoradiotherapy (CRT) is the standard of care for limited-stage small cell lung cancer (LS-SCLC). Local therapy-surgery or stereotactic body radiotherapy (SBRT)-with adjuvant chemotherapy may be appropriate for very early (T1-T2, N0) disease. There is variability in the management of these cases, which may lead to variability in patient outcomes. This study aimed to determine practice patterns for the management of very early LS-SCLC in Canada. A survey was developed and distributed to Canadian medical and radiation oncologists specialising in lung cancer. The survey consisted of three sections: (1) physician demographics, (2) general practice approach, and (3) preferred approach for three clinical scenarios (1: peripheral T1 lesion; 2: central T1 lesion; 3: peripheral T2 lesion). Responses were analysed to detect differences across cases and among physician groups. There were 77 respondents. In case 1, assuming medical operability, most respondents (73%) chose surgery and adjuvant chemotherapy, with 19% choosing CRT. CRT was selected by a higher proportion in case 2 (48%) and case 3 (61%) (p < 0.05). If medically inoperable, most chose CRT over local therapy in all cases, with more choosing CRT in case 2 (84%) and case 3 (86%) than in case 1 (55%) (p < 0.05). Subgroup analysis showed a predilection towards CRT in Western Canada and among more experienced physicians, and towards SBRT in Ontario. There is variability in the management of very early LS-SCLC in Canada. CRT remains the most popular strategy in most cases, with surgery preferred for small peripheral lesions. Larger and more central tumours are more likely to be managed with CRT. Variation in practice is correlated with region and physician experience. Our study illustrates the variability in the management of very early LS-SCLC in Canada and highlights the need for more robust investigations into the ideal approach for these patients.

Factor H preserves alternative complement function during ARDS, linked to improved survival.

Background: Effective regulation of complement activation may be crucial to preserving complement function during acute respiratory distress syndrome (ARDS). Factor H is the primary negative regulator of the alternative pathway of complement. We hypothesised that preserved factor H levels are associated with decreased complement activation and reduced mortality during ARDS. Methods: Total alternative pathway function was measured by serum haemolytic assay (AH50) using available samples from the ARDSnet Lisofylline and Respiratory Management of Acute Lung Injury (LARMA) trial (n=218). Factor B and factor H levels were quantified using ELISA using samples from the ARDSnet LARMA and Statins for Acutely Injured Lungs from Sepsis (SAILS) (n=224) trials. Meta-analyses included previously quantified AH50, factor B and factor H values from an observational registry (Acute Lung Injury Registry and Biospecimen Repository (ALIR)). Complement C3, and complement activation products C3a and Ba plasma levels were measured in SAILS. Results: AH50 greater than the median was associated with reduced mortality in meta-analysis of LARMA and ALIR (hazard ratio (HR) 0.66, 95% CI 0.45-0.96). In contrast, patients in the lowest AH50 quartile demonstrated relative deficiency of both factor B and factor H. Relative deficiency of factor B (HR 1.99, 95% CI 1.44-2.75) or factor H (HR 1.52, 95% CI 1.09-2.11) was associated with increased mortality in meta-analysis of LARMA, SAILS and ALIR. Relative factor H deficiency was associated with increased factor consumption, as evidenced by lower factor B and C3 levels and Ba:B and C3a:C3 ratios. Higher factor H levels associated with lower inflammatory markers. Conclusions: Relative factor H deficiency, higher Ba:B and C3a:C3 ratios and lower factor B and C3 levels suggest a subset of ARDS with complement factor exhaustion, impaired alternative pathway function, and increased mortality, that may be amenable to therapeutic targeting.

Submitting a Manuscript to a Scientific Journal.

This review guides prospective authors through the necessary steps to submit a paper to a scientific journal. The journey to publication begins with selecting a journal to submit the manuscript. Considerations when choosing a journal include appropriateness, determining whether a given journal is an ethical and high-quality publication, measurements of journal ranking or impact, and other factors such as associated author costs or high rejection rates. The importance of reading and following the author guidelines is highlighted because they outline the journal's overarching editorial policies and scope of publication, and provide journal-specific instructions for manuscript preparation. Strategies for successful submission as well as common pitfalls to avoid are shared, with specific tips applicable to submitting a paper to Respiratory Care Finally, insights into what the editor wants may guide authors as they seek publication.

A Case of Cutaneous Vasculitis in the Setting of Systemic Lupus Erythematosus and Cocaine Use.

Cocaine, one of most prevalent illicit substances in the United States, affects a multitude of organ systems and precedes numerous negative health outcomes. Many of the consequences of cocaine are linked to induction of vasoconstriction. For this reason, cocaine users are placed at considerable risk of ischemic stroke, myocardial infarction, and cardiac arrhythmias. Furthermore, a prominent contaminant, levamisole, has been widely implicated in predisposing individuals to developing or exacerbating cutaneous vasculitides. This report details a 31-year-old woman with acute, localized necrotic skin lesions after cocaine use. Her clinical picture was complicated by a 17-year history of systemic lupus erythematosus (SLE) and Raynaud's phenomenon. This case examines the challenge of forming a differential diagnosis, initiating an appropriate workup, and interpreting serologic-based and immunologic-based studies to differentiate between SLE and drug-based etiologies of skin necrosis. Finally, we discuss appropriate treatment plans to mitigate symptoms and reduce future instances of drug-induced vasculitis.

Improved uptake and survival with systemic treatments for metastatic non-small cell lung cancer: younger versus older adults.

BACKGROUND: Over the past decade, there has been increasing availability of novel therapeutics with improved tolerability and efficacy for advanced non-small cell lung cancer (NSCLC). The study goals were: to compare the uptake of systemic therapy (ST) before and after the availability of targeted tyrosine kinase inhibitors (TKI) and immunotherapy and to examine the changes in overall survival (OS) over time between younger and older adults with advanced NSCLC. METHODS: All patients with advanced NSCLC referred to British Columbia (BC) Cancer in 2009, 2011, 2015 and 2017 were included. One-year time points were based on molecular testing implementation and funded drug availability: baseline (2009), epidermal growth factor receptor TKI (2011), anaplastic lymphoma kinase TKI (2015) and Programed Death-1 (PD-1) inhibitors (2017). Age groups were <70years and ≥70years. Baseline demographics, simplified comorbidity scores (SCS), disease characteristics, and ST details were collected retrospectively. Variables were compared using X2, Fisher's exact tests and logistic-regression analysis. OS was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: 3325 patients were identified. Baseline characteristics were compared between ages < 70 years and ≥ 70 years for each time cohort with significant differences noted in baseline Eastern Cooperative Oncology Group (ECOG) performance status and SCS. The rate of ST delivery trended upwards over time with age <70 years: 2009 44%, 2011 53%, 2015 50% and 2017 52% and age ≥70 years: 22%, 25%, 28% and 29% respectively. Predictors for decreased use of ST for age <70 years: ECOG ≥2, SCS ≥9, year 2011, and smoking history; and age ≥70 years: ECOG ≥2, years 2011 and 2015, and smoking history. The median OS of patients who received ST improved from 2009 to 2017: age <70 years 9.1 m vs. 15.5 m and age ≥70 years 11.4 m vs. 15.0 m. CONCLUSIONS: There was an increased uptake of ST for both age groups with the introduction of novel therapeutics. Although a smaller proportion of older adults received ST, those who received treatment had comparable OS to their young counterpart. The benefit of ST in both age groups was seen across the different types of treatments. With careful assessment and selection of appropriate candidates, older adults with advanced NSCLC appear to benefit from ST.

A systematic review and meta-analysis of factors influencing ImPACT concussion testing in high school and collegiate athletes with self-reported ADHD and/or LD.

OBJECTIVE: Sport concussion is a common injury, and athletes with attention-deficit/hyperactivity disorder (ADHD) and/or learning disorder (LD) are at increased risk and require specialized attention in clinical settings. Although systematic reviews of the relationship between ADHD/LD and concussion are reported in the literature, these reviews do not include quantitative syntheses. Additionally, no reviews have focused on the most commonly utilized concussion assessment, Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). The current review provides an update of sport concussion assessment in athletes with ADHD and/or LD from 2000 to 2021 on these topics: baseline and postconcussion performance on ImPACT, baseline and postconcussion symptom reporting using the Postconcussion Symptom Scale, invalid baseline classification on ImPACT, and self-reported history of concussion. METHOD: Meta-analyses were conducted on baseline ImPACT performance, symptom reporting, invalid baseline classification, and concussion rates. Thirty-four studies were included in systematic review and 19 were included in meta-analyses. RESULTS: Decreased baseline performance was found for athletes with ADHD (trivial to small effects), LD (small-to-medium effects), and ADHD/LD (small-to-medium effects). Increased baseline symptom reporting was found for athletes with ADHD (small effect). Increased odds of invalid baseline performance (trivial effect) and self-reported concussion history (small effect) were found in ADHD. CONCLUSIONS: These results provide the first quantitative synthesis of the literature in this area. It is recommended that future research further examines these topics in athletes with LD and co-occurring ADHD/LD (given the focus on ADHD), as well as the effects that all of these conditions may have on concussion recovery and return-to-play decision-making. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Real-World Immunotherapy Use and Effectiveness in Advanced NSCLC With Programmed Death-Ligand 1 Greater Than or Equal to 50% and Greater Than or Equal to 90.

Background: Immunotherapy has vastly changed the treatment landscape for patients with advanced NSCLC. With high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥50%), options include programmed cell death protein 1 or PD-L1 inhibitor with or without chemotherapy. A cut-point of greater than or equal to 50% defines PD-L1-high, but a more precise PD-L1 tumor proportion score may be an important predictor of outcomes. Methods: We reviewed all patients with PD-L1-high NSCLC who received pembrolizumab from June 2019 to June 2021. Demographic, diagnosis, treatment, and outcomes data were collected retrospectively. The primary end point was a descriptive analysis of pembrolizumab prescribing patterns. Secondary end points included overall survival (OS) by treatment choice and absolute PD-L1 expression. Results: Overall, 132 patients received pembrolizumab; 124 (94%) as monotherapy, and 8 (6%) with chemotherapy. Baseline characteristics include the following: (1) median age 70 years (50-89); (2) 55% men; (3) 79% Eastern Cooperative Oncology Group performance status 0 to 1; and (4) 96% current or former smokers. There were 39% who have PD-L1 greater than or equal to 90% versus 61% with PD-L1 of 50% to 89%. The median OS in the overall population was 14.4 months. The median OS in the pembrolizumab monotherapy cohort and combination cohort were 13.6 months and 16.6 months, respectively (p = 0.67). Within the monotherapy cohort, the median OS was longer for PD-L1 greater than or equal to 90% (19.8 mo) versus PD-L1 50% to 89% (11.9 mo, p = 0.039). The 24-month OS was 27.8% among patients with PD-L1 50% to 89% and 47.4% among patients with PD-L1 greater than or equal to 90%. Conclusions: Most patients with advanced PD-L1-high NSCLC received pembrolizumab monotherapy, among whom OS was strongly correlated with PD-L1 expression, with PD-L1 greater than or equal to 90% of patients experiencing substantially longer survival. PD-L1 expression level could be an important determinant in immunotherapy prescribing patterns and a predictor of success in advanced NSCLC.

Complex Germline K757N Mutation in Non-Small-Cell Lung Cancer: A Case Report.

Epidermal growth factor receptor (EGFR) mutations are usually oncogenic drivers of lung tumor development and progression. While common sensitizing mutations respond well to targeted therapy, the relevance of germline EGFR mutations is less clear. We describe a 65-year-old, previously healthy, male diagnosed with non-small-cell lung cancer. Familial history for lung cancer is negative. Targeted next-generation sequencing on the tumor biopsy sample revealed an atypical EGFR K757N mutation at 50% allele frequency and genetic review of a previously acquired gastric sample confirms the mutation as a germline change. He received standard first-line chemoimmunotherapy with carboplatin, pemetrexed, and pembrolizumab, and after 8 months therapy continues, with stable disease, to receive maintenance pemetrexed and pembrolizumab. To our knowledge, this is the first report of an atypical, germline K757N EGFR mutation. While the clinical relevance of this mutation is unclear, standard reporting of the allelic frequency of novel, atypical mutations can detect potential germline changes.

Clinicopathological features of pulmonary mucinous adenocarcinoma: A descriptive analysis.

BACKGROUND: Mucinous adenocarcinoma is a rare subtype of lung cancer characterized by abnormal mucin production. We sought to investigate the clinical and pathological features of pulmonary mucinous adenocarcinomas and to identify prognostic factors. METHODS: This was a single-institution retrospective review of patients with pulmonary mucinous adenocarcinoma diagnosed between January 1, 2015 and December 31, 2020. Descriptive analysis included demographics, diagnostic data, and treatment modalities. The primary outcome was overall survival (OS). RESULTS: Fifty-six patients were included in the study. Median age was 65 years (range: 26-84), 30 (54%) were female, 48 (86%) had a smoking history, and 41 (73%) patients had ECOG performance status 0-1. Nearly half (26, 46%) were stage IV at presentation, while 11 (20%) presented as stage I, 10 (18%) stage II, and 9 (16%) stage III. Biomarker testing increased through the study period. Where performed, 4/48 (8%) cases were ALK positive, but there were no EGFR cases identified (0/36). Only 3/20 cases had PD-L1 expression >50%. Curative intent therapy was performed in 23 patients (17 had surgery +/- chemotherapy/radiation, 4 had radiotherapy alone, 2 had chemoradiation). Median OS in the entire population was 16.1 months (m). OS by stage was 50.0m for stage I, not reached for stage II, 20.7m for stage III, and 8.1m for stage IV. CONCLUSIONS: The overall prognosis of pulmonary mucinous adenocarcinoma appears similar to that of non-mucinous adenocarcinomas, with distinct differences noted in the incidence of oncogenic driver mutations, particularly an absence of EGFR mutations.

Brief Report: Medical Assistance in Dying in Patients With Lung Cancer.

INTRODUCTION: Medical assistance in dying (MAiD) was legalized in Canada in 2016. Cancer accounts for 60% to 65% of MAiD cases. Lung cancer, the most common cause of cancer death, is expected to makeup a large number of MAiD cases. Lung cancer treatment has advanced in recent years; however, involvement of oncology specialists and use of systemic therapy in patients who receive MAiD are unknown. METHODS: All patients with lung cancer referred to the Champlain Regional MAiD Program from June 17, 2016, to November 30, 2020, were reviewed. Baseline demographics, diagnostic, referral, and treatment details were collected by retrospective review. Coprimary end points were the proportion of patients who met a medical oncologist or who received systemic therapy. RESULTS: During the study period, 255 patients with cancer underwent MAiD. Of these, 45 (17.6%) had lung cancer, comprising our final study population. Baseline characteristics: median age 72 years, 64% female, 85% former or current smoking history, 82% non-small cell, 4% small cell, and 13% clinical diagnosis without biopsy. Most patients (78%) were seen by a medical oncologist, though only 16 (36%) received systemic therapy for advanced disease. In subpopulations of interest, 45% of patients with programmed death-ligand 1 greater than or equal to 50% received immunotherapy and 75% with an oncogenic driver mutation received targeted therapy. There were 26 patients (58%) who had a documented discussion with their oncologist regarding the transition to best supportive care. CONCLUSIONS: Most patients with lung cancer are assessed by an oncology specialist before MAiD, though less than half received systemic therapy. Among patients with more treatable forms of lung cancer, many patients still undergo MAiD without accessing, or in some cases being assessed for, these treatment options.

Effect of targeted therapy and immunotherapy on advanced nonsmall-cell lung cancer outcomes in the real world.

The evolution of diagnosis and treatment of advanced nonsmall-cell lung cancer (NSCLC) has led to increasing the use of targeted therapy and immune checkpoint inhibitors. The study goal was to assess the effect of molecular testing and the introduction of new therapies on overall survival (OS). All patients with stage IV NSCLC referred to BC Cancer were included in the study. Four 1-year time cohorts were created based on molecular testing implementation and funded drug availability: C1 baseline (2009), C2 EGFR TKI access (2011), C3 ALK inhibitor access (2015), C4 immunotherapy availability (2017). Baseline demographics, disease characteristics, and systemic therapy details were collected retrospectively. OS was calculated using the Kaplan-Meier method and compared using the log-rank test. There were 3421 patients identified with stage IV NSCLC and 1319 (39%) received systemic therapy. In the four 1-year time cohorts C1/C2/C3/C4: driver mutation-targeted treatment increased 1/17/27/34% (of total systemic therapy), as did treatment with any line immunotherapy <1/1/9/38%. Median OS with best supportive care (BSC) was 3.4/3.1/3.2/2.9 m (p = 0.16) and with systemic treatment 9.9/10.9/13.9/15.0 m (p < 0.001). Median OS by treatment exposure was BSC 3.1 m, chemotherapy only 7.3 m, targeted therapy 17.5 m, and immunotherapy 20.7 m. In our real-world study, following the introduction of targeted therapy and immune checkpoint inhibitors, there was a significant improvement in OS in each successive time cohort concordant with advancements in therapeutic options.

Stereotactic Body Radiotherapy (SBRT) in Very Limited-Stage Small Cell Lung Cancer (VLS-SCLC).

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumour with metastatic propensity. Stereotactic body radiation therapy (SBRT) is an emerging therapeutic option for SCLC, despite limited supporting evidence. By evaluating the use of SBRT in very limited stage (VLS) SCLC at our institution, we aimed to contribute to the existing knowledge in this area while establishing a basis for further research. We performed a retrospective review of all cases of VLS-SCLC treated with SBRT between 2013 and 2020. Baseline demographics, diagnostic, and treatment information were collected. The primary outcome was overall survival (OS). We identified 46 patients with pathologically confirmed VLS-SCLC; 25 were treated with SBRT, and the remainder received either surgery, conventional radiation therapy, chemotherapy, or palliative-intent therapy. After a median follow-up of 23.7 months, 44% of the patients had died; the median OS was of 24.4 months for the SBRT cohort and 67.0 months for the curative intent non-SBRT cohort. The difference in disease recurrence and survival between cohorts was underpowered and not statistically significant. Higher baseline ECOG and comorbidity was noted in the SBRT cohort.

A novel assay that characterizes properdin function shows neutrophil-derived properdin has a distinct oligomeric distribution.

Properdin acts as an essential positive regulator of the alternative pathway of complement by stabilizing enzymatic convertases. Identical properdin monomers form head-to-tail associations of oligomers in a reported 20:54:26 ratio (most often described as an approximate 1:2:1 ratio) of tetramers (P4), trimers (P3), and dimers (P2), in blood, under normal physiological conditions. Oligomeric size is proportional to properdin function with tetramers being more active, followed by trimers and dimers. Neutrophils are the most abundant granulocyte, are recruited to inflammatory microenvironments, and are a significant source of properdin, yet the ratio of properdin oligomers released from neutrophils is unknown. The oligomer ratio of neutrophil-derived properdin could have functional consequences in local microenvironments where neutrophils are abundant and complement drives inflammation. We investigated the oligomer properties of neutrophil-derived properdin, as compared to that of normal human sera, using a novel ELISA-based method that detects function of properdin in a way that was proportional to the oligomeric size of properdin (i.e., the larger the oligomer, the higher the detected function). Unexpectedly, neutrophil-derived properdin had 5-fold lower function than donor-matched serum-derived properdin. The lower function was due to a lower percentage of tetramers/trimers and more dimers, indicating a significantly different P4:P3:P2 ratio in neutrophil-derived properdin (18:34:48) as compared to donor-matched serum (29:43:29). Release of lower-order oligomers by neutrophils may constitute a novel regulatory mechanism to control the rate of complement activation in cellular microenvironments. Further studies to determine the factors that affect properdin oligomerization and whether, or how, the predominant dimers in neutrophil-derived properdin, assimilate to the ~1:2:1 ratio found in serum are warranted.

The need for speed in advanced non-small cell lung cancer: A population kinetics assessment.

BACKGROUND: Systemic therapy prolongs overall survival (OS) in advanced non-small cell lung cancer (NSCLC), but diagnostic tests, staging and molecular profiling take time, and this can delay therapy initiation. OS approximates first-order kinetics. METHODS: We used OS of chemo-naive NSCLC patients on a placebo/best supportive care trial arm to estimate % of patients dying while awaiting therapy. We digitized survival curves from eight studies, calculated OS half-life, then estimated the proportion surviving after different times of interest (tn ) using the formula: X=exp-tn∗0.693/t1/2 , where EXP signifies exponential, * indicates multiplication, 0.693 is the natural log of 2, and t1/2 is the survival half-life in weeks. RESULTS: Across trials, the OS half-life for placebo/best supportive care in previously untreated NSCLC was 19.5 weeks. Hence, based on calculations using the formula above, if therapy were delayed by 1, 2, 3, or 4 weeks then 4%, 7%, 10%, and 13% of all patients, respectively, would die while awaiting treatment. Others would become too sick to consider therapy even if still alive. CONCLUSIONS: This quantifies why rapid baseline testing and prompt therapy initiation are important in advanced NSCLC. It also illustrates why screening procedures for clinical trial inclusion must be faster. Otherwise, it is potentially hazardous for a patient to be considered for a trial due to risk of death or deterioration while awaiting eligibility assessment. It is also important to not delay initiation of systemic therapy for procedures that add relatively little value, such as radiotherapy for small, asymptomatic brain metastases.