Kuhnhenson0912
The nuclear exporter protein exportin-1 (XPO1) is overexpressed in non-Hodgkin lymphoma (NHL) and correlates with poor prognosis. We evaluated enhancing R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) activity in NHL by targeted inhibition of XPO1 using the selective inhibitor of nuclear export (SINE) compounds.
We evaluated the antitumor activity of SINE compounds in combination with CHO chemotherapy
and
. Newly diagnosed NHL patients in a phase I dose-escalation study received R-CHOP for 6 cycles with weekly selinexor (60, 80, and 100 mg), then selinexor maintenance therapy for one year. RT-PCR, Western blotting, and RNA sequencing were performed on patient blood samples.
SINE compounds synergized with CHO
in NHL cell lines and
in our murine xenograft model. In our phase I study, selinexor was dosed at 60 mg (
= 6) and 80 mg (
= 6). The most common adverse events (AE) among 12 patients were fatigue (67%) and nausea (100%). Grade 3-4 AEs were infrequent. Ten evaluable patients had an overall response rate of 100% and complete remission rate of 90% with sustained remissions (median follow-up 476 days). Maximally tolerated dose was not reached; however, the recommended phase II dose was 60 mg selinexor weekly after evaluating tolerability and discontinuation rates for each dose cohort. Analysis of patient blood samples revealed downregulation of XPO1 and several prosurvival markers.
SINE compounds enhance the activity of CHO
and
. Selinexor in combination with R-CHOP was generally well tolerated and showed encouraging efficacy in NHL (NCT03147885).
SINE compounds enhance the activity of CHO in vitro and in vivo. Selinexor in combination with R-CHOP was generally well tolerated and showed encouraging efficacy in NHL (NCT03147885).
The mTOR complex C1 (mTORC1) inhibitor everolimus in combination with the aromatase inhibitor exemestane is an effective treatment for patients with hormone receptor-positive (HR
), HER2-negative (HER2
), advanced breast cancer (HR
/HER2
aBC). However, everolimus can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/protein kinase B (AKT)/mTORC1 pathway and induce tumor resistance to everolimus.
We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first 3 months of therapy) blood glucose levels on progression-free survival (PFS) in patients with HR
/HER2
aBC treated with everolimus-exemestane.
We evaluated 809 patients with HR
/HER2
aBC treated with everolimus-exemestane as any line of therapy for advanced disease. When evaluated as dichotomous variables, baseline and on-treatment glycemia were not significantly associated with PFS. However, when blood glucose concentration was evaluated as a contients with HR+/HER2- aBC depends on baseline glycemia. This study lays the foundations for investigating novel therapeutic approaches to target the glucose/insulin axis in combination with PI3K/AKT/mTORC1 inhibitors in patients with HR+/HER2- aBC.
To investigate the toxicity profile and establish an optimal dosing schedule of zotiraciclib with temozolomide in patients with recurrent high-grade astrocytoma.
This two-stage phase I trial determined the MTD of zotiraciclib combined with either dose-dense (Arm1) or metronomic (Arm2) temozolomide using a Bayesian Optimal Interval design; then a randomized cohort expansion compared the progression-free survival rate at 4 months (PFS4) of the two arms for an efficient determination of a temozolomide schedule to combine with zotiraciclib at MTD. Pharmacokinetic and pharmacogenomic profiling were included. Patient-reported outcome was evaluated by longitudinal symptom burden.
Fifty-three patients were enrolled. Dose-limiting toxicities were neutropenia, diarrhea, elevated liver enzymes, and fatigue. MTD of zotiraciclib was 250 mg in both arms and thus selected for the cohort expansion. Dose-dense temozolomide plus zotiraciclib (PSF4 40%) compared favorably with metronomic temozolomide (PFS4 25%). Symptom by allow personalized dosing of zotiraciclib.
It is unclear what the best strategy is for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among residents of homeless shelters and what individual factors are associated with testing positive for the virus. selleck inhibitor We sought to evaluate factors associated with testing positive for SARS-CoV-2 among residents of homeless shelters and to evaluate positivity rates in shelters where testing was conducted in response to coronavirus disease 2019 (COVID-19) outbreaks or for surveillance.
We conducted a retrospective chart audit to obtain repeated cross-sectional data from outreach testing done at homeless shelters between Apr. 1 and July 31, 2020, in Toronto, Ontario, Canada. We compared the SARS-CoV-2 positivity rate for shelters where testing was conducted because of an outbreak (at least 1 known case) with those tested for surveillance (no known cases). A patient-level analysis evaluated differences in demographic, health and behavioural characteristics of residents who did and did not test poymptomatic shelter residents for SARS-CoV-2 when a positive case is identified at the same shelter. Surveillance testing when there are no known positive cases may detect outbreaks, but further research should identify efficient strategies given scarce testing resources.
The quality of case reports, which are often the first reported evidence for a disease, may be negatively affected by a rush to publication early in a pandemic. We aimed to determine the completeness of reporting (COR) for case reports published on coronavirus disease 2019 (COVID-19).
We conducted a systematic search of the PubMed database for all single-patient case reports of confirmed COVID-19 published from Jan. 1 to Apr. 24, 2020. All included case reports were assessed for adherence to the CARE (Case Report) 31-item checklist, which was used to create a composite COR score. The primary outcome was the mean COR score assessed by 2 independent raters. Secondary outcomes included whether there was a change in overall COR score with certain publication factors (e.g., publication date) and whether there was a linear relation between COR and citation count and between COR scores and social media attention.
Our search identified 196 studies that were published in 114 unique journals. We found that the overall mean COR score was 54.4%. No one case report included all of the 31 CARE checklist items. There was no significant correlation between COR with either citation count or social media attention.
We found that the overall COR for case reports on COVID-19 was poor. We suggest that journals adopt common case-reporting standards to improve reporting quality.
We found that the overall COR for case reports on COVID-19 was poor. We suggest that journals adopt common case-reporting standards to improve reporting quality.
Nurse practitioners (NPs) have been regulated primary care providers in British Columbia since 2005; however, many practices and contributions of NPs, especially those in northern or rural regions, remain unarticulated in primary health care. The objective of this study was to evaluate NP practices in the context of providing primary health care in northern BC.
This was a qualitative-dominant mixed-methods study. We recruited NP participants working in northern BC; recruitment and data collection occurred between April and June 2018. Participants completed the validated 28-item Primary Health Care Engagement (PHCE) Scale to assess their perceptions of their workplace with 8 attributes of primary health care (quality improvement, community participation, patient-centred care, accessibility, intersectoral team, interdisciplinary collaboration, continuity and population orientation). We also interviewed NPs about their everyday practice. Transcribed data from the interviews were analyzed interpretively.
Inh care.In the last 5 years, artificial intelligence (AI) algorithms have made rapid advances for diagnosis and prognosis in fields ranging from dermatology to anesthesiology. How do we make sense of the rise of AI in healthcare and specifically in spine? How much of what we see today is "hype" and what will remain when the dust settles? In this special issue, several reviews and original articles help us understand the state of AI in healthcare today, the avenues for future progress, and the implications for spine care. Continued engagement, skepticism, and collaboration with technical experts will allow for the development of AI systems that complement and expand our abilities to diagnose, predict, and operate.
The minimally invasive (MI) approach in posterior lumbar interbody fusion (PLIF) minimizes the muscle-stripping posterior exposure of the lumbar spine; therefore, it is hypothesized that such benefits would reduce adjacent segment pathology (ASP) development.
This study aimed to estimate the incidence of ASP following MI-PLIF.
Retrospective study.
A total of 100 patients who had undergone single-level PLIF at the L4/5 level for lumbar degenerative spondylolisthesis were retrospectively studied (MI-PLIF group 68 patients; conventional open PLIF [O-PLIF] group; 32 patients; average follow-up period 100.5 months).
Incidence of ASP.
Patients were considered to have operative ASP (OASP) if adjacent segments manifested degenerative lesions that caused clinically significant symptoms requiring surgery. Survival curves were estimated for each group using the Kaplan-Meier method. The study was not externally funded. The authors have no conflicts of interest to declare.
Four (5.9%) of the 68 patients in t O-PLIF.
Psychological comorbidities are important prognostic factors for low back pain (LBP). To develop improved treatment paradigms, it is first necessary to characterize and determine current patterns of treatment in this population.
Identify how comorbid depression or anxiety in patients with LBP is related to use of healthcare resources.
Retrospective cohort study using electronic health records from outpatient offices at a large multisite academic medical center.
Data from 513,088 unique patients seen between January 2010 and July 2020 (58.0% female, 52.6±19.5 years) with a diagnosis of LBP, indicated by predetermined ICD-9 and ICD-10 codes.
Average self-reported pain scores, absolute differences and unadjusted risk ratios to compare opioid use, emergency department visits, hospitalizations, advanced imaging orders, spinal injections, and back surgeries between cohorts.
Clinical characteristics and data regarding use of healthcare resources were extracted from the electronic health record. Clinical iated with clinically meaningful elevated pain scores. Limitations come from use of an aggregate data set and reliance on administrative coding.
Previous studies have found that cervical sagittal parameters and spinal cord compression are important risk factors for cervical spondylotic myelopathy (CSM). An increasing number of scholars believe that cervical muscle condition is also one of the factors affecting the severity of symptoms in affected patients.
To determine whether the degree of corresponding segmental paravertebral muscle degeneration is related to the severity of symptoms in patients with CSM; the degree of cervical spinal cord compression can predict the severity of symptoms in patients with CSM.
A retrospective study.
From January 2015 to January 2019, 121 patients with CSM were enrolled.
The visual analog scale (VAS), neck disability index (NDI) and modified Japanese Orthopedic Association (mJOA) were used to assess cervical spinal function and quality of life.
From January 2015 to January 2019, 121 patients with CSM were enrolled. The inclusion criterion was the presence of complete cervical lateral radiography and magnetic resonance imaging (MRI) data.
