Citations

Drug-induced movement disorders affect a significant percentage of individuals, and they are commonly overlooked and underdiagnosed in clinical practice. Many comorbidities can affect these individuals, making the diagnosis even more challenging. Several variables, including genetics, environmental factors, and aging, can play a role in the pathophysiology of these conditions. The Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Statistical Classification of Diseases and Related Health Problems (ICD) are the most commonly used classification systems in categorizing drug-induced movement disorders. This literature review aims to describe the abnormal movements associated with some medications and illicit drugs. Myoclonus is probably the most poorly described movement disorder, in which most of the reports do not describe electrodiagnostic studies. Therefore, the information available is insufficient for the diagnosis of the neuroanatomical source of myoclonus. Drug-induced parkinsonism is rarely adequately evaluated but should be assessed with radiotracers when these techniques are available. Tardive dyskinesias and dyskinesias encompass various abnormal movements, including chorea, athetosis, and ballism. Some authors include a temporal relationship to define tardive syndromes for other movement disorders, such as dystonia, tremor, and ataxia. Antiseizure medications and antipsychotics are among the most thoroughly described drug classes associated with movement disorders.

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

Abstract Objective Frailty, characterized by multi-system decline, increases vulnerability to adverse health outcomes and can be measured using Frailty Index (FI). We aimed to assess the prevalence of frailty in patients with adrenal disorders (based on hormonal sub-type) and examine association between FI and performance-based measures of physical function. Design Multi-centre, cross-sectional study (March 2019-August 2022). Methods Adult patients with adrenal disorders (non-functioning adrenal adenomas [NFA], mild autonomous cortisol secretion [MACS], Cushing syndrome [CS], primary aldosteronism [PA]) and referent subjects without adrenal disorders completed a questionnaire encompassing 47 health variables (comorbidities, symptoms, daily living activities). FI was calculated as the average score of all variables and frailty defined as FI ≥ 0.25. Physical function was assessed with hand grip, timed up-and-go test, chair rising test, 6-minute walk test, and gait speed. Results Compared to referent subjects (n = 89), patients with adrenal disorders (n = 520) showed increased age, sex, and body mass index-adjusted prevalence of frailty (CS [odds ratio—OR 19.2, 95% confidence interval—CI 6.7-70], MACS [OR 12.5, 95% CI 4.8-42.9], PA [OR 8.4, 95% CI 2.9-30.4], NFA [OR 4.5, 95% CI 1.7-15.9]). Prevalence of frailty was similar to referent subjects when post-dexamethasone cortisol was <28 nmol/L and was higher when post-dexamethasone cortisol was 28-50 nmol/L (OR 4.6, 95% CI 1.7-16.5). FI correlated with all measures of physical function (P < .001). Conclusions Whilst frailty prevalence was highest in patients with adrenocortical hormone excess, even patients with NFA demonstrated an increased prevalence compared to the referent population. Future longitudinal studies are needed to evaluate the impact of various management strategies on frailty.

Abstract Purpose: Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) interaction has led to durable responses in fewer than half of patients with mismatch repair–deficient (MMR-d) advanced colorectal cancers. Immune contexture, including spatial distribution of immune cells in the tumor microenvironment (TME), may predict immunotherapy outcome. Experimental Design: Immune contexture and spatial distribution, including cell-to-cell distance measurements, were analyzed by multiplex immunofluorescence (mIF) in primary colorectal cancers with d-MMR (N = 33) from patients treated with anti–PD-1 antibodies. By digital image analysis, density, ratio, intensity, and spatial distribution of PD-L1, PD-1, CD8, CD3, CD68, LAG3, TGFβR2, MHC-I, CD14, B2M, and pan-cytokeratin were computed. Feature selection was performed by regularized Cox regression with LASSO, and a proportional hazards model was fitted to predict progression-free survival (PFS). Results: For predicting survival among patients with MMR-d advanced colorectal cancer receiving PD-1 blockade, cell-to-cell distance measurements, but not cell densities or ratios, achieved statistical significance univariately. By multivariable feature selection, only mean number of PD-1+ cells within 10 μm of a PD-L1+ cell was significantly predictive of PFS. Dichotomization of this variable revealed that those with high versus low values had significantly prolonged PFS [median not reached (>83 months) vs. 8.5 months (95% confidence interval (95% CI), 4.7–NR)] with a median PFS of 28.4 months for all patients [adjusted HR (HRadj) = 0.14; 95% CI, 0.04–0.56; P = 0.005]. Expression of PD-1 was observed on CD8+ T cells; PD-L1 on CD3+ and CD8+ T lymphocytes, macrophages (CD68+), and tumor cells. Conclusions: In d-MMR colorectal cancers, PD-1+ to PD-L1+ receptor to ligand proximity is a potential predictive biomarker for the effectiveness of PD-1 blockade.

AbstractModulating the nerve's local microenvironment using exosomes is proposed to enhance nerve regeneration. This study aimed to determine the optimal dose of purified exosome product (PEP) required to exert maximal neurite extension. An in vitro dorsal root ganglion (DRG) neurite outgrowth assay was used to evaluate the effect of treatment with (i) 5% PEP, (ii) 10% PEP, (iii) 15% PEP, or (iv) 20% PEP on neurite extension (N = 9/group), compared to untreated controls. After 72 h, neurite extension was measured to quantify nerve regeneration. Live cell imaging was used to visualize neurite outgrowth during incubation. Treatment with 5% PEP resulted in the longest neurite extension and was superior to the untreated DRG (p = 0.003). Treatment with 10% PEP, 15% PEP, and 20% PEP was found to be comparable to controls (p = 0.12, p = 0.06, and p = 0.41, respectively) and each other. Live cell imaging suggested that PEP migrated towards the DRG neural regeneration site, compared to the persistent homogenous distribution of PEP in culture media alone. 5% PEP was found to be the optimal concentration for nerve regeneration based on this in vitro dose–response analysis.

Abstract Importance and Objective Despite a decreasing incidence of cervical cancer in North America overall, disparities in screening and cervical cancer rates persist, especially in the postmenopausal age group. Methods We reviewed the literature regarding cervical cancer screening considerations for postmenopausal persons, with a focus on cervical cancer in postmenopausal persons, existing guidelines, screening methods, and gaps in care. Discussion and Conclusion Postmenopausal persons are an important population at risk because age 65 years in the United States and up to 70 years in some parts of Canada is a milestone for screening cessation if the criteria are met. Unfortunately, inadequate screening is common, with most women 65 years or older discontinuing (exiting) screening despite not meeting the criteria to do so. Screening cessation recommendations are nuanced, and if not all criteria are met, screening should be continued until they are. Cervical cancer screening should be stopped at the recommended age if adequate screening has occurred or at any age if life expectancy is limited or the patient has had a hysterectomy in the absence of high-grade preinvasive cervical lesions or cervical cancer. Human papillomavirus infection, which is causally linked to almost all cervical cancer cases, can persist or reactivate from a prior infection or can be newly acquired from sexual contact. With more persons aging with a cervix in place, the potential for cervical cancer has increased, and higher cancer rates may be observed if recommended screening is not adhered to. We propose an algorithm based on current cervical cancer screening guidelines to aid providers in identifying whether exit criteria have been met. Until adequate screening has been confirmed, cervical cancer screening should continue.

Objectives: Desirable outcomes following surgery for anterior shoulder instability (ASI) include a multitude of functional and clinical functions, yet it remains uncertain if all of these outcomes are simultaneously achievable (i.e. can patients have full motion and no instability; does excellent stability coincide with stiffness?). The purpose of this study was to employ unsupervised machine learning techniques to define the actual "optimal observed outcome” for patients undergoing surgical treatment for ASI and to identify predictors of obtaining this outcome. Methods: Patients <40 years with an initial diagnosis of ASI from 1994 -2016 were included. Four unsupervised machine learning clustering algorithms were evaluated to partition subjects into “optimal observed outcome” or “suboptimal outcome” based on combinations of actually observed outcomes. Demographic, clinical, and treatment variables were compared between groups using descriptive statistics and Kaplan-Meier survival curves; multivariate stepwise logistic regression evaluated variable prognostic value. Results: 200 patients with a mean follow-up of 11 years were included. 146 (64%) obtained the “optimal observed outcome”, characterized by significantly (P <0.001) lower rates of: recurrent postoperative pain (23% vs 52%), recurrent instability (12% vs 41%), revision surgery (10% vs 24%), progression to osteoarthritis (OA) (5% vs. 19%), and mildly restricted motion (161° vs. 168°). Stepwise multivariate logistic regression identified time from initial instability to presentation (OR: 0.96, 95% CI: 0.92-0.98) and habitual instability (OR: 0.17, 95%CI: 0.04-0.77) as negative predictors of “observed optimal outcome”. Increased rate of subluxation over frank dislocation pre-operatively (OR: 1.30, 95% CI: 1.02-1.65) was a positive predictor. Type of surgery performed was not a significant predictor. Conclusions: Following surgical treatment for ASI, an appropriate “optimal observed outcome” can be defined as: minimal postoperative pain, absence of recurrent instability, low rates of revision surgery, absence of OA, and increased ROM. This “optimal observed outcome” was achieved in over 2/3rds of the cohort and this work demonstrated the synergistic relationship of these. The most significant predictors included shorter time to presentation and history of subluxations over frank dislocations pre-operatively. This definition of the “optimal observed outcome” may be more appropriate for surgical decision making and setting appropriate expectations. [Table: see text][Table: see text]

AbstractBACKGROUNDDelirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long‐term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology.METHODSThe Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts.RESULTSMeeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium‐spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations.DISCUSSIONThe DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes.Highlights Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.