The microRNA-34 Family and Its Functional Role in Lung Cancer.

Lung cancer is one of the most common malignant tumors in humans and the leading cause of cancer-related deaths worldwide. The microRNA-34 (miR-34) family is dysregulated in various human cancers and is an important family of tumor suppressor genes among microRNAs. The miR-34 family is downregulated in lung cancer. It inhibits cell proliferation, metastasis, and invasion, arrests the cell cycle, and induces apoptosis or senescence by negatively regulating many oncogenes. It is commonly used to detect and treat lung cancer. This study describes the regulatory role of the miR-34 family in lung cancer and the associated research advances in treatment.

Five-Year Serial Brain MRI Analysis of Military Members Exposed to Chronic Sub-Concussive Overpressures.

BACKGROUND: The Canadian Special Operations Forces Command conducts explosives operations and training which exposes members to explosive charges at close proximity. This 5-year longitudinal trial was conducted in follow-up to our initial trial which examined military breachers with MRI and EEG pre and post blast exposure. PURPOSE: To examine brain MRI findings in military personnel exposed to multiple repeated blast exposures. STUDY TYPE: Five-year longitudinal prospective trial. POPULATION: Ninety-two males aged 23-42 with an average of 9.4 years of blast exposure. FIELD STRENGTH/SEQUENCE: 3 T brain MRI/T1-weighted 3D with reconstruction in three planes, T2-weighted, T2-weighted fluid attenuated inversion recovery (FLAIR) 3D with reconstruction in three planes, T2-weighted gradient spin echo (GRE), saturation weighted images, DWI and ADC maps, diffusion tensor imaging. ASSESSMENT: All MRI scans were interpreted by the two neuroradiologists and one neuroradiology Fellow in a blinded fashion using a customized neuroradiology reporting form. STATISTICAL TESTS: Matching parametric statistics represented the number of participants whose brain parameters improved or deteriorated over time. Odds ratio (OR) and 95% confidence intervals (CI) were computed using log regression modeling to determine volume loss, white matter lesions, hemosiderosis, gliosis, cystic changes and enlarged Virchow Robin (VR) spaces. A Kappa (κ) statistic with a 95% CI was calculated to determine rater variability between readers. RESULTS: A significant deterioration was observed in volume loss (OR = 1.083, 95% CI 0.678-1.731, permutation test), white matter changes (OR: 0.754, 95% CI 0.442-1.284, permutation test), and enlargement of VR spaces (OR: 0.775, 95% CI 0.513-1.171). Interrater reliability was low: κ = 0.283, 0.156, and 0.557 for volume loss, white matter changes, and enlargement of VR spaces, respectively. DATA CONCLUSION: There were significant changes in brain volume, white matter lesions, and enlargement of VR spaces. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

A 15-Year Single-Institution Retrospective Study of Primary Pancreatic Cancer Treated with Non-Ablative Palliative Radiotherapy.

We studied the use of palliative radiotherapy (RT) among patients with primary, non-curable, locally advanced pancreatic cancer. In this subset of patients, with very poor survival, various palliative RT dose fractionation schemes are used; but, in the absence of a guideline, practice patterns vary, and dose choice is mainly based on the physician's intuition. We divided the patients into three groups, according to the dose fractionation schedules received: low (A), intermediate (B), and high (C) dose groups, to study the potential differences in outcome between the different dose prescriptions. Cohort: n = 184. Median age: 69 years. Male: n = 105 (57%), female: n = 79 (43%). Stage IV: n = 117 (64%). T4: n = 127 (69%). Tumor location: head: n = 109 (59%), body: n = 37 (20%), tail: n = 25 (14%), neck: n = 11 (6%), and uncinate: n = 2 (1%). Prior systemic therapy: n = 66 (36%). Most common dose fractionations received: 20 Gy in five fractions n = 67 (36%), 30 Gy in 10 fractions n = 49 (27%), and 8 Gy in one fraction n = 23 (13%). Group A: n = 33 (18%), median overall survival (OS) 19 days (95% CI 4-33). Group B: n = 84 (46%), median OS 52 days (95% CI 43-60). Group C: n = 67 (36%), median OS 126 days (95% CI 77-174). Median days to in-field progression: Group A 59 days (range 7-109), Group B 96 days (range 19-173), and Group C 97 days (range 13-475). To our knowledge, this is the largest reported retrospective cohort of patients receiving non-ablative palliative RT to treat their primary pancreatic tumors. Most patients had metastatic disease, T4 tumors of the pancreatic head and had not received prior systemic therapy. A significant survival benefit was seen favoring the high dose/longer RT fractionation group, presumably due to appropriate patient selection rather than an RT effect. Despite the relatively short median overall survival, one fifth of the patients were found to experience an in-field progression following RT.

Real-world practices in reproductive health and counselling for women with epilepsy: A Canadian perspective.

Canadian women of reproductive potential living with epilepsy present unique care challenges due to the complex interplay of hormones, seizures, and medications. This study explores reproductive health practices and counselling for women with epilepsy. Through a questionnaire developed by the Canadian League Against Epilepsy women with epilepsy (WWE) workgroup, we are the first to report demographic and real-world practice characteristics of Canadian healthcare professionals providing care for WWE with specific focus on family planning, birth plans, and postpartum care counselling. Among respondents, 76.9% routinely reviewed contraception with patients and an intrauterine device (IUD) was the most popular recommended method (85.3%). With regards to preconception planning, 50% of respondents routinely had a preconception drug level prior to pregnancy. A significant proportion, 44.9%, reported not communicating a neurology-informed birth plan to obstetrical health practitioners. The majority recommended breastfeeding for WWE on anti-seizure medications (92.3%) and regularly provided safety counselling for women in the postpartum period (84.6%). Overall, our study demonstrates that Canadian practice patterns conform reasonably well to existing evidence and guidelines, although important gaps in care exist.

Real-world practices for the care of women with epilepsy during pregnancy: A Canadian perspective.

OBJECTIVE: Approximately 150,000 Canadian women live with epilepsy, a population that presents with unique challenges. Our objective was to capture demographic and real-world practice characteristics of Canadian healthcare professionals providing care for women with epilepsy (WWE) with specific focus on reproductive considerations to identify potential gaps in knowledge and care. METHODS: A questionnaire developed by the Canadian League Against Epilepsy WWE workgroup was distributed to Canadian healthcare professionals from February 2021 to October 2022 to capture participant demographic characteristics and practice patterns in key areas of the reproductive cycle in WWE. RESULTS: A total of 156 participants completed the questionnaire, most being physicians (81.4%), epilepsy specialists (69.0%), and those who cared for adult patients (86.5%), with a significant proportion based at an academic center (65.4%). The majority of participants counselled on folic acid supplementation (89.7%). Participants selected lamotrigine and levetiracetam most frequently for either focal or generalized epilepsies during pregnancy. Additionally, 85.9% performed therapeutic drug monitoring during pregnancy. Almost all practitioners always or often counseled WWE on valproic acid on the benefits of switching to a less teratogenic medication (96.2%). Some geographic variability in practice patterns was noted with valproic acid being one of the top three medications selected for patients with generalized epilepsies in Western regions, although participants in Eastern regions had brivaracetam more commonly included as one of their top three agents for this population. SIGNIFICANCE: This is the first report of real-world Canadian practices in epilepsy care for women in pregnancy. Overall, our study reports that Canadian practice patterns conform well to current evidence and best-practice guidelines. Important variations in antiseizure medication selection across different regions were identified.

Study on creep characteristics and component model of saline soil in hexi corridor.

Accurate mastery of the creep characteristics of unsaturated saline soil is extremely important for the long-term stability and safe operation of all types of buildings. In this paper, the research object focused on the saline soil of the Zhangye area, Hexi corridor. The indoor triaxial CU creep test was carried out by means of graded loading to study the creep characteristics of saline soil under different salt content and loading stress. The Merchant and Burgers models were used to predict the creep behavior of the saline soils, and the predicted results were compared with the experimental values. The results showed that the triaxial creep curve of saline soil developed in stage III. Namely, transient creep stage, deceleration creep stage and steady-state creep stage. The creep deformation increases with the increase of salt content and loading stress. The stress-strain isochronous curve has non-linear growth, and the cluster of curves develops from dense to sparse after increasing to long-term strength (100∼150 kPa). The parameters of the Merchant and Burgers model vary with salt content and loading stress, and the creep curve predicted by the Burgers model is closer to the test value.

Acute spinal cord infarction secondary to ankylosing spondylitis: a case report and literature review.

Introduction: Spinal cord infarction secondary to ankylosing spondylitis is a rare but severe disorder. Case presentation: Here we present a case of acute spinal cord infarction in a 54 years-old man with a medical history of ankylosing spondylitis, scoliosis, and hypotension. The patient complained of a sudden onset of lower limb weakness. A physical examination showed that he suffered from a dissociative sensory disorder, paralysis, and concomitant sphincter disturbances. After undergoing a whole-spine MRI, he was diagnosed with an acute ischemic injury from T2 to T5. As he did not treat his ankylosing spondylitis, it later caused a spinal deformity, making the lumbar puncture technically challenging. However, using Taylor's approach, a CSF sample was successfully obtained. A CSF biochemical test ruled out myelitis, NMOSD, and MS. After receiving treatment with low-molecular-weight heparin, atorvastatin calcium, and methylprednisolone, his sphincter function gradually recovered, but his strength was only partially restored. Conclusion: Although this is a rare entity, it is necessary for physicians to consider it when evaluating patients with a sudden loss of sensation and strength in their lower limbs.

What Attributes Matter Most in Physicians? Exploratory Findings from a Single-Centre Survey of Stakeholder Priorities in Cancer Care at a Canadian Academic Cancer Centre.

BACKGROUND: Limited research exists regarding how healthcare stakeholders prioritize the importance of differing physician attributes in oncologists. Identifying these priorities can help ensure that Canadian cancer care continues to meet the needs of its patients. In our previous research, compassion and empathy were identified as important physician attributes, with answers like knowledge, professionalism or communication less common. We hypothesized that respondents may have been assuming other, underlying qualities in their oncologists when they prioritized "compassion" and "empathy". To test this, the current study asks respondents to rank important physician attributes. METHODS: With ethics approval, we asked healthcare stakeholders (physicians, nurses, patients, caregivers, medical students, and allied healthcare providers) to rank the eight most popular qualities or attributes. We identified differences between which characteristics each group valued most in physicians. RESULTS: 375 respondents participated in the survey. "Knowledge" and "competence" were the most popular answers in the current study among all groups except medical students. CONCLUSION: Previously, we identified compassion as a highly valued attribute; however, this survey suggests that this may be with the assumption that a physician is knowledgeable and competent. Future research will use semi-structured interviews to investigate respondents' rationales for making their choices and help interpret our findings in this study.

Complexity in clinical diagnoses of acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a clinical syndrome with various causes. It is not uncommon that COPD patients presenting with dyspnea have multiple causes for their symptoms including AECOPD, pneumonia, or congestive heart failure occurring concurrently. METHODS: To identify clinical, radiographic, and laboratory characteristics that might help distinguish AECOPD from another dominant disease in patients with a history of COPD, we conducted a retrospective cohort study of hospitalized patients with admitting diagnosis of AECOPD who were screened for a prospective randomized controlled trial from Sep 2016 to Mar 2018. Clinical characteristics, course in hospital, and final diagnosis at discharge were reviewed and adjudicated by two authors. The final diagnosis of each patient was determined based on the synthesis of all presenting signs and symptoms, imaging, and laboratory results. We adhered to AECOPD diagnosis definitions based on the GOLD guidelines. Univariate and multivariate analyses were performed to identify any associated features of AECOPD with and without other acute processes contributing to dyspnea. RESULTS: Three hundred fifteen hospitalized patients with admitting diagnosis of AECOPD were included. Mean age was 72.5 (SD 10.6) years. Two thirds (65.4%) had spirometry defined COPD. The most common presenting symptom was dyspnea (96.5%), followed by cough (67.9%), and increased sputum (57.5%). One hundred and eighty (57.1%) had a final diagnosis of AECOPD alone whereas 87 (27.6%) had AECOPD with other conditions and 48 (15.2%) did not have AECOPD after adjudication. Increased sputum purulence (OR 3.35, 95%CI 1.68-6.69) and elevated venous pCO2 (OR 1.04, 95%CI 1.01 - 1.07) were associated with a diagnosis of AECOPD but these were not associated with AECOPD alone without concomitant conditions. Radiographic evidence of pleural effusion (OR 0.26, 95%CI 0.12 - 0.58) was negatively associated with AECOPD with or without other conditions while radiographic evidence of pulmonary edema (OR 0.31; 95%CI 0.11 - 0.91) and lobar pneumonia (OR 0.13, 95%CI 0.07 - 0.25) suggested against the diagnosis of AECOPD alone. CONCLUSION: The study highlighted the complexity and difficulty of AECOPD diagnosis. A more specific clinical tool to diagnose AECOPD is needed.

Outcomes for Malignant Pleural Effusions Because of Melanoma Treated With Indwelling Pleural Catheters.

BACKGROUND: Indwelling pleural catheters (IPCs) reduce dyspnea and improve quality of life in patients with malignant pleural effusions (MPEs). Data on outcomes of MPEs secondary to metastatic melanoma managed with IPCs are scarce. We aimed to evaluate outcomes of patients receiving IPCs for MPEs secondary to melanoma compared with other malignancies. METHODS: We identified patients from our prospectively collected database of all patients who had an IPC insertion for MPEs at our tertiary care center for melanoma between May 2006 and November 2018 and for nonmelanoma between May 2006 and June 2013. Chart reviews were conducted to obtain patient demographics, catheter complications, time of IPC removal or death, x-ray imaging, and pleural fluid characteristics. RESULTS: We identified 27 MPEs because of melanoma and 1114 because of nonmelanoma malignancies treated with IPC. The most frequent complication was pleural fluid loculation requiring fibrinolytics which was significantly higher in the melanoma (14.8%) compared with the nonmelanoma group (3.8%; P =0.02). Cumulative incidence functions for catheter removal ( P =0.8) or death with catheter in situ ( P =0.3) were not significant between melanoma and nonmelanoma groups in competing risk analysis. Baseline radiographic pleural effusion scores were similar, but became significantly higher (increased pleural opacity) in the melanoma group at time points following IPC insertion ( P <0.05). CONCLUSION: MPEs because of melanoma had a higher rate of loculations requiring fibrinolytics and less radiographic improvement after IPC insertion suggesting this patient subgroup has a more complicated pleural space which may be less responsive to drainage.

Ultrasound-determined healing rates with subscapularis tenotomy versus peel after anatomic shoulder arthroplasty.

BACKGROUND: Several techniques have been described for mobilizing the subscapularis tendon in anatomic total shoulder arthroplasty (TSA). The purpose of this study was to compare subscapularis tendon healing rates, as determined by ultrasound, in patients following anatomic TSA with either a subscapularis tenotomy or subscapularis peel. METHODS: This study was a secondary analysis of patients from a previous randomized controlled trial in which patients underwent anatomic TSA and were randomized to either a tenotomy or peel approach. The primary outcome was postoperative tendon healing rates determined on ultrasound at >12 months after surgery. Secondary outcomes included postoperative tendon thickness measured on ultrasound; elbow position (neutral alignment in the belly-press position vs. posterior); internal rotation function measured with the third and fourth questions of the American Shoulder and Elbow Surgeons questionnaire; and Western Ontario Osteoarthritis of the Shoulder index. Radiographs were analyzed in patients with torn tendons. RESULTS: One hundred patients were randomized to a tenotomy (n = 47) or peel (n = 53) approach. Postoperative ultrasound results were available in 88 patients. Tendon healing rates were 95% for tenotomy vs. 75% for peel (P = .011). The mean postoperative tendon thickness was 4 mm (standard deviation, 1.0 mm) and 4 mm (standard deviation, 1 mm) in the tenotomy and peel groups, respectively (P = .37). Internal rotation function was not associated with healing status (P = .77 and P = .22 for questions 3 and 4, respectively, of the American Shoulder and Elbow Surgeons questionnaire), nor was elbow position (P = .2) in the belly-press position. DISCUSSION: We observed that subscapularis tenotomy had a higher healing rate than peel as determined by ultrasound in TSA patients. There was no statistically significant difference in postoperative tendon thickness in intact tendons as measured on ultrasound when comparing subscapularis mobilization techniques, nor was there any association between healing status and internal rotation function or elbow position.

Evaluation of Surgical Approaches and Use of Adjuvant Radiotherapy with Respect to Oncologic Outcomes in the Management of Clinically Early-Stage Cervical Carcinoma.

The standard of care for early-stage cervix cancer is radical hysterectomy with pelvic lymphadenectomy. Adjuvant radiotherapy (RT) or chemoradiotherapy may be administered to reduce the risk of recurrence in patients considered to be at elevated risk based on a combination of pathologic factors. We performed a retrospective review to determine oncologic outcomes in patients treated for early-stage cervix cancer and to determine if surgical approach impacted oncologic outcomes or the decision to use adjuvant therapy. In total, 174 women underwent radical hysterectomy and pelvic lymphadenectomy over the 15-year period. Most of these women (146) had open surgery and 28 had minimally invasive surgery (MIS). In total, 81 had adjuvant pelvic RT; 76 in the open surgery group (52%) and 5 in the MIS group (18%). Five-year PFS and OS, respectively, were 84% and 91%. Five-year PFS was significantly lower in patients who had MIS vs. open surgery, without a difference in 5-year OS, suggesting MIS should be avoided. Five-year PFS was the same with RT or with its omission, despite those treated with RT having higher risk disease. We have demonstrated excellent outcomes in patients with early-stage cervix cancer after primary surgery and selective use of RT, with few recurrences and excellent survival.

The Association between Intertwin Difference in First Trimester Crown-Rump Length, Nuchal Translucency, and Birth Weight Discordance in Twin Pregnancies: A Retrospective Cohort Study.

Background: Discordant birth weight in twins is linked to poor outcomes and predicting this discrepancy may lead to enhanced screening and surveillance. Our purpose was to quantify the relationship between intertwin nuchal translucency (NT) and crown-rump length (CRL) discordance with birth weight discrepancies ≥ 20%. Methods: We conducted a retrospective cohort study of 887 live twin births delivering at a Canadian tertiary care center over a 7-year period who opted for integrated prenatal screening. Categorical data are presented as numbers and percentages, and continuous data are expressed as means and standard deviations. Chi-square tests, Fisher's Exact tests, or T-test were performed as appropriate. We then used published data and receiver operating curves to determine the optimal thresholds for predicting birth weight discordance based on first trimester intertwin NT differences. These values were used in multivariate logistic regression models accounting for known confounders. Results: Roughly 16% of twin pairs exhibited ≥ 20% difference in birth weight. Twin pairs with a CRL discordance greater than 10% have nearly a 4 times greater likelihood of having a birth weight discordance greater than 20% (OR 3.71, CI 2.24-6.14) while controlling for chorionicity, maternal age, gestational age at delivery, maternal body mass index (BMI), and parity. In these models, intertwin NT discordance ≥ 20% (OR 1.16, CI 0.77-1.77) and NT discordance ≥ 14% (OR 1.08, CI 0.73-1.60) were not statistically significant predictors of twin birth weight differences. However, when evaluating the effect of the larger intertwin NT value corresponding to the 95th percentile, an NT difference ≥ 0.9 mm was predictive of birth weight discordance ≥ 20% (OR 2.53, CI 1.21-5.29). Conclusion: Although intertwin CRL and NT discordance measured via ultrasound between 11-14 weeks gestation are related to birth weight discordance, there is uncertainty as to whether twin birth weight differences are related to adverse pregnancy outcomes in this population.

Mindfulness-Based Stress Reduction in Breast Cancer Survivors with Chronic Neuropathic Pain: A Randomized Controlled Trial.

Objectives: The purpose of this study was to compare the effects of group-delivered mindfulness-based stress reduction as compared to a waitlist control group among breast cancer survivors living with CNP. Methods: A randomized controlled trial design was applied, and outcomes collected included pain, emotional function, quality of life, and global impression of change. Results: A total of 98 women were randomized and included in analyses. The sample included 49 women in the mindfulness-based stress reduction group, and 49 women in the waitlist control group. The intervention group participants (mean age 51.3 years, standard deviation = 11.4) and waitlist participants (mean age 55.1 years, standard deviation = 9.6) reported an average pain duration of approximately three years. No significant differences were found on the primary outcome of the proportions of women with reduced pain interference scores from the time of randomization to 3 months after the intervention was received. No significant changes were found among secondary outcomes. Conclusion: Our randomized clinical trial did not find significant benefits of group-based mindfulness-based stress reduction for the management of CNP. The current study findings should be replicated and are important to consider given ongoing concerns that nonsignificant results of mindfulness-based stress reduction are often unpublished.

Does late second-trimester cervical length predict unscheduled preterm birth in asymptomatic triplet pregnancies?

OBJECTIVE: Multiple gestation increases the risk of unscheduled preterm birth (PTB), both spontaneous and indicated, leading to increased neonatal morbidity and additional healthcare costs. The purpose of this study was to determine whether cervical length (CL) assessment by 28 weeks could predict unscheduled PTB <34 weeks in triplet pregnancies. Secondary outcomes included prediction of PTB <30 weeks, prediction of PTB based on degree of cervical change and effect of ART-use on PTB. METHODS: This was a retrospective cohort of women with triplet pregnancies. The exposure variable of interest was short cervix < 25 and <20 millimeters (mm) by 28 weeks. Maternal characteristics were described. The distribution of CLs was analyzed by the primary outcome of unscheduled PTB < 34 weeks, and by PTB <30 weeks (secondary outcome). Gestational age at delivery was compared between women with and without a short cervix. Changes in CL were compared between the groups with unscheduled PTB and those delivering ≥34 and ≥30 weeks. Statistical analyses were performed using appropriate tests. RESULTS: Of 92 triplet pregnancies, 51 met the criteria, with 1233 total (411 shortest) CL measurements from 16 to 34 weeks' gestation. The overall rate of PTB <34 weeks was 31.4% and <30 weeks was 9.8%. The median gestational age at delivery was 32.7 (IQR 2.3) weeks. There were no statistically significant differences in rates of unscheduled PTB in women who had a short cervix and those that did not: PTB <34 weeks with CL <25 mm (p = .53) and CL <20 mm (p = .70); PTB <30 weeks with CL <25 mm (p = .38) and CL <20 mm (p = .26). The degree of cervical change from 18 to 28 weeks was not statistically significant for predicting unscheduled PTB <34 and <30 weeks. Of 70.6% of triplet pregnancies conceived by ARTs, 13.9% had unscheduled PTB <30 weeks, whereas no spontaneously-conceived pregnancies delivered <30 weeks (p = .14). CONCLUSION: Short cervix did not predict unscheduled spontaneous PTB <34 weeks nor <30 weeks in our triplet cohort, nor did the degree of cervical change by 28 weeks predict PTB. Triplets conceived by ARTs may have an increased risk of unscheduled PTB.

A Multicenter Randomized Controlled Trial Comparing Single-Row With Double-Row Fixation in Arthroscopic Rotator Cuff Repair: Long-Term Follow-up.

BACKGROUND: The long-term outcomes of single- versus double-row fixation in arthroscopic rotator cuff repair are not currently known. PURPOSE: To compare the treatment effects of the single- versus double-row suture technique in arthroscopic rotator cuff repair of full-thickness tears at 10-year follow-up. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Patients were evaluated at 10 years postoperatively. The primary outcome measure was the Western Ontario Rotator Cuff Index (WORC). Secondary outcome measures included the American Shoulder and Elbow Surgeons (ASES) score, Constant score, strength, and incidence of revision surgery. Ultrasound was used to evaluate the rotator cuff to determine repair integrity. Statistical analyses consistent with those of the main trial were conducted. RESULTS: Of the original 90 participants, 77 (85%) returned at a mean follow-up of 10 years. At ten year follow-up, the WORC score was higher in the double row group (79.9 [95% CI, 16.2 to 99.1]) compared with the single row group (72.9, [95% CI, 4.3 to 100]), P = .020. From baseline to 2 years, the mean change in WORC scores for the single-row group was -48.5 compared with -40.6 for the double-row group, with a between-group difference of -7.8 (95% CI, -20.4 to 4.7). From 2 to 10 years, the change in WORC scores for the single-row group was 11.5 compared with -0.2 for the double-row group, with a between-group difference of 11.7 (95% CI, -0.7 to 24.3). From baseline to 10 years, the mean between-group difference was 3.9 (95% CI, -7.8 to 15.6). Similarly, a decrease in ASES scores was observed between 2 and 10 years for the single-row group (9.2 [95% CI, 0.9 to 17.5]; P = .029), with a nonsignificant decrease in ASES scores for the double-row group (6.2 [95% CI, -3.2 to 15.6]; P = .195) as well as a decrease in Constant scores for both the single- (9.5 [95% CI, 1.4 to 17.5]; P = .020) and double-row (14.4 [95% CI, 5.6 to 23.3]; P = .001) groups. Overall, 3 participants developed a full-thickness tear after 2 years: 2 from the double-row group and 1 from the single-row group. One participant from each study group underwent revision surgery after the 2-year time point. CONCLUSION: A statistically significant (but likely not clinically important) difference in WORC scores was seen at 10-year follow-up in favor of double-row fixation. Between baseline and 10-year follow-up, a decrease in most outcome scores was observed in both the single- and the double-row groups. REGISTRATION: NCT00508183 (ClinicalTrials.gov identifier).

Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B cell acute lymphoblastic leukemia.

How metabolic status controls the fates of different types of leukemia cells remains elusive. Using a SoNar-transgenic mouse line, we demonstrated that B cell acute lymphoblastic leukemia (B-ALL) cells had a preference in using oxidative phosphorylation. B-ALL cells with a low SoNar ratio (SoNar-low) had enhanced mitochondrial respiration capacity, mainly resided in the vascular niche, and were enriched with more functional leukemia-initiating cells than that of SoNar-high cells in a murine B-ALL model. The SoNar-low cells were more resistant to cytosine arabinoside (Ara-C) treatment. cyclic adenosine 3',5'-monophosphate response element-binding protein transactivated pyruvate dehydrogenase complex component X and cytidine deaminase to maintain the oxidative phosphorylation level and Ara-C-induced resistance. SoNar-low human primary B-ALL cells also had a preference for oxidative phosphorylation. Suppressing oxidative phosphorylation with several drugs sufficiently attenuated Ara-C-induced resistance. Our study provides a unique angle for understanding the potential connections between metabolism and B-ALL cell fates.

Adjuvant melatonin for the prevention of recurrence and mortality following lung cancer resection (AMPLCaRe): A randomized placebo controlled clinical trial.

BACKGROUND: Despite curative intent resection in patients with non-small cell lung cancer (NSCLC), recurrence leading to mortality remains too common. Melatonin has shown promise for the treatment of patients with lung cancer; however, its effect following cancer resection has not been studied. We evaluated if melatonin taken after complete resection reduces lung cancer recurrence and mortality, or impacts quality of life (QOL), symptomatology or immune function. METHODS: Participants received melatonin (20 mg) or placebo nightly for one year following surgical resection of primary NSCLC. The primary outcome was two-year disease-free survival (DFS). Secondary outcomes included five-year DFS, adverse events, QOL, fatigue, sleep, depression, anxiety, pain, and biomarkers assessing for immune function/inflammation. This study is registered at https://clinicaltrials.gov NCT00668707. FINDINGS: 709 patients across eight centres were randomized to melatonin (n = 356) versus placebo (n = 353). At two years, melatonin showed a relative risk of 1·01 (95% CI 0·83-1·22), p = 0·94 for DFS. At five years, melatonin showed a hazard ratio of 0·97 (95% CI 0·86-1·09), p = 0·84 for DFS. When stratified by cancer stage (I/II and III/IV), a hazard reduction of 25% (HR 0·75, 95% CI 0·61-0·92, p = 0·005) in five-year DFS was seen for participants in the treatment arm with advanced cancer (stage III/IV). No meaningful differences were seen in any other outcomes. INTERPRETATION: Adjuvant melatonin following resection of NSCLC does not affect DFS for patients with resected early stage NSCLC, yet may increase DFS in patients with late stage disease. Further study is needed to confirm this positive result. No beneficial effects were seen in QOL, symptoms, or immune function. FUNDING: This study was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation.

How Canadian Oncologists Use Oncotype DX for Treatment of Breast Cancer Patients.

BACKGROUND: The literature suggests that medical oncologists differ on how they use the Oncotype DX (ODX) genomic assay for making decisions about systemic therapy in breast cancer patients. Given the emergence of data supporting the use of genomic profiling for the prognosis and predicting benefit of chemotherapy, we surveyed medical oncologists in Canada to assess their usage and perception of the ODX assay. METHODS: A 34-item survey was distributed to Canadian medical oncologists via the Canadian Association of Medical Oncologists. Data was collected on physician demographics, ODX usage patterns, and physicians' perception of the impact clinical and pathologic characteristics make on ODX utilization. RESULTS: Response rate was 20.6% with 47 responses received from 228 survey sent. Forty-five responses were eligible for analysis. Sixty-two percent (28/45) of respondents treated predominantly breast cancer, and 60% (27/45) have been in practice for at least 10 years. The most cited reason for using ODX was to avoid giving patients unnecessary chemotherapy (64%; 29/45). Sixty-seven percent (30/45) deferred making treatment decisions until ODX testing was completed. Factors most strongly impacting ODX utilization included: patient request, medical comorbidities and tumor grade. In clinical scenarios, ODX was more frequently selected for patients aged 40-65 (vs. <40 or >65), grade 2 tumors (vs. grade 1 or 3), and Ki-67 index of 10-20% (vs. <10% or >20%). CONCLUSIONS: This survey demonstrated that Canadian medical oncologists are preferentially using ODX to avoid giving patients unnecessary chemotherapy. The utilization of ODX is mainly in patients with intermediate clinical and pathologic features.