Negative Clinical Implications Research Articles

Readmission rates following major colorectal surgery

BackgroundReadmissions following colorectal surgery (CRS) have negative clinical, psychological and financial implications. Identifying patients at risk of readmission remains challenging. AimsTo determine factors predictive of those likely to require readmission at 40-days following major CRS and to identify novel strategies capable of reducing readmissions. MethodsConsecutive patients were studied from a prospectively maintained database. All patients were operated on by a single surgeon in a high-volume centre. Where applicable, photography was recorded by patients and emailed directly to the institutional email of the consultant surgeon. Data was recorded and analysed using descriptive statistics. Results515 patients were included over a 15-year period (2007-2022). The mean age at surgery was 64 years (18-93). The majority of patients were male (56.9%, n=293) and underwent cancer surgery (58.2%, n=299). Overall, 55 patients were readmitted within 40 days of major CRS (10.7%). Patients with pre-treatment diagnoses of heart failure (P=0.012), ischemic heart disease (P=0.002), renal impairment (P<0.001), atrial fibrillation (P=0.006), hypercholesterolemia (P=0.001), asthma (P=0.013) and hypertension (P=0.001) were more likely to require readmission. The majority of patients were readmitted for definitive management of surgical site issues (SSIs) (43.7% n=24). Other reasons included bowel obstruction (9.1%, n=5), pelvic sepsis (7.3%, n=4) and gastrointestinal upset (7.3%, n=4). ConclusionThis series demonstrated that patients with cardiopulmonary comorbidities were more likely to be readmitted following major CRS and most readmissions are SSI related. Readmissions for SSIs can be reduced by patients sending photography to the treating surgeon which could reduce readmissions and A&E attendances.

Projecting the Clinical and Economic Impacts of Changes to HIV Care Among Adolescents and Young Adults in the United States: Lessons From the COVID-19 Pandemic.

During the COVID-19 pandemic, many US youth with HIV (YHIV) used telehealth services; others experienced disruptions in clinic and antiretroviral therapy (ART) access. Using the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Adolescent HIV microsimulation model, we evaluated 3 scenarios: 1) Clinic: in-person care; 2) Telehealth: virtual visits, without CD4 or viral load monitoring for 12 months, followed by return to usual care; and 3) Interruption: complete care interruption with no ART access or laboratory monitoring for 6 months (maximum clinic closure time), followed by return to usual care for 80%. We assigned higher 1-year retention (87% vs 80%) and lower cost/visit ($49 vs $56) for Telehealth vs Clinic. We modeled 2 YHIV cohorts with non-perinatal (YNPHIV) and perinatal (YPHIV) HIV, which differed by mean age (22 vs 16 years), sex at birth (85% vs 47% male), starting CD4 count (527/μL vs 635/μL), ART, mortality, and HIV-related costs. We projected life months (LMs) and costs/100 YHIV over 10 years. Over 10 years, LMs in Clinic and Telehealth would be similar (YNPHIV: 11 350 vs 11 360 LMs; YPHIV: 11 680 LMs for both strategies); costs would be $0.3M (YNPHIV) and $0.4M (YPHIV) more for Telehealth than Clinic. Interruption would be less effective (YNPHIV: 11 230 LMs; YPHIV: 11 620 LMs) and less costly (YNPHIV: $1.3M less; YPHIV: $0.2M less) than Clinic. Higher retention in Telehealth led to increased ART use and thus higher costs. Telehealth could be as effective as in-person care for some YHIV, at slightly increased cost. Short interruptions to ART and laboratory monitoring may have negative long-term clinical implications.

General and abdominal obesity trends in the Iranian adult population from 2004 to 2021.

The prevalence of overweight/obesity and abdominal obesity is increasing worldwide, accompanied by an increase in the incidence of non-communicable diseases. This study aims to determine the trends of Body Mass Index (BMI) and prevalence of overweight/obesity and abdominal obesity changes in Iranian adult population from 2004 to 2021. We conducted this study based on the eight national surveys of noncommunicable disease risk factor surveillance (STEPS) from 2004 to 2021 in Iran. We estimated the crude and standardized mean of BMI and prevalence of general and abdominal obesity in these eight STEPS surveys data. Data weighted using post-stratification method and the trends depicted based on the standardized estimates. Between 2004 and 2021, and based on the standardized estimates, the mean of BMI increased from 25.19kg/m2 in 2004 to 26.63kg/m2 in 2021 (P-value for trend = 0.03). The standardized mean of WC increased from 86.38cm in 2004 to 91.65cm in 2021 (P-value for trend = 0.38). The standardized prevalence of obesity (class I and II) increased from 14.54% in 2004 to 20.17% in 2021 (P-value for trend = 0.01). The standardized prevalence of obesity class III increased from 0.82% in 2004 to 1.35% in 2021 (P-value for trend = 0.03). The standardized prevalence of abdominal obesity based on the national and international cut-points increased, but the trend was not statistically significant [(National cut-point: 27.53% in 2004 to 40.43% in 2021 (P-value for trend = 0.71)) (International cut-point: 27.58% in 2004 to 41.81% in 2021 (P-value for trend = 0.06))]. The standardized mean of BMI and prevalence of overweight/obesity and abdominal obesity increased among Iranian adults between 2004 and 2021. Because of the negative public and clinical health implications of obesity, health policymakers should develop comprehensive programs to control this increasing trend of weight gain.

AB033. SOH23ABS_042. Readmission rates following major colorectal surgery and using clinical photography as a pragmatic solution

Background: Readmissions following colorectal surgery (CRS) have negative clinical, psychological and financial implications. Identifying patients at risk of readmission remains challenging. To determine factors predictive of those likely to require readmission at 40 days following major CRS and to identify novel strategies capable of reducing readmissions.

Implications of research that excludes under-served populations.

Effective translation of evidence from clinical trials into clinical practice requires the enrolment of diverse, representative trial populations. However, this diversity is still often lacking, with negative clinical implications for under-served groups. Changes are needed to research practices and the broader research landscape to correct this problem.

The use of ultrasound, fibronectin and other parameters to predict the success of labour induction.

Induction of labour is a common obstetrical procedure and is undertaken when the benefits of delivery are considered to outweigh the risks of continuation of pregnancy. However, more than one-fifth of induction cases fail to result in vaginal births and lead to unplanned caesarean deliveries, which compromise the birth experience and have negative clinical and resource implications. The need for accurate prediction of successful labour induction is increasingly recognised and many researchers have attempted to evaluate the potential predictability of different factors including maternal characteristics, Bishop score, various biochemical markers and ultrasound markers and derive predictive models to address this issue.

Clinical outcomes following switching antipsychotic treatment due to market withdrawal: a retrospective naturalistic cohort study of pipotiazine palmitate injection (Piportil Depot) discontinuation, subsequent acute care use and effectiveness of medication to which patients switched.

Introduction:Pipotiazine palmitate depot injection (Piportil) was withdrawn from the UK marketplace in 2015. Few studies exist on the clinical impact of such market withdrawal. Purpose: We aimed to identify a cohort of patients switching from pipotiazine following this withdrawal and explore factors associated with effectiveness of the medication switched to and subsequent acute service use.Methods:A naturalistic retrospective cohort study was conducted in Sussex, United Kingdom. Those discontinuing pipotiazine solely due to market withdrawal were identified from electronic patient database and manual searching. Multivariate logistic regression analyses and survival analyses were performed to explore associations between available baseline variables and dichotomous all-cause discontinuation of the next prescribed medication and admission to acute mental health services over the subsequent year.Results:Of 205 patients identified as receiving pipotiazine in October 2014, 137 switched from this due to market withdrawal. Over the subsequent year, 31.5% discontinued the medication to which they were switched and 19% required acute care. Drug class switched to (typical depot vs atypical long acting injection (LAI) vs atypical oral) had no significant association with discontinuation. Switch to atypical LAI was significantly associated with acute care in comparison to typical depot. Those with a schizophrenia diagnosis were significantly less likely to discontinue switched medication or to receive acute care in comparison to those with schizoaffective disorder. Women were significantly more likely to discontinue switched medication than men. Of those requiring acute care, only 38% had required this in the previous 2 years.Conclusions:Antipsychotic market withdrawal has demonstrable negative clinical implications and requires careful clinical management. Increased acute care rates in those receiving an atypical LAI versus a typical depot following pipotiazine suggests lower effectiveness or possible withdrawal effects. No significant difference between depots, LAIs and oral medications on discontinuation supports the importance of a collaborative, fully informed approach when deciding next treatment options.

Effects of in vitro short- and long-term treatment with telomerase inhibitor in U-251 glioma cells.

The inhibition of the enzyme telomerase (TERT) has been widely investigated as a new pharmacological approach for cancer treatment, but its real potential and the biochemical consequences are not totally understood. Here, we investigated the effects of the telomerase inhibitor MST-312 on a human glioma cell line after both short- and long-term (290 days) treatments. Effects on cell growth, viability, cell cycle, morphology, cell death and genes expression were assessed. We found that short-term treatment promoted cell cycle arrest followed by apoptosis. Importantly, cells with telomerase knock-down revealed that the toxic effects of MST-312 are partially TERT dependent. In contrast, although the long-term treatment decreased cell proliferation at first, it also caused adaptations potentially related to treatment resistance and tumor aggressiveness after long time of exposition. Despite the short-term effects of telomerase inhibition not being due to telomere erosion, they are at least partially related to the enzyme inhibition, which may represent an important strategy to pave the way for tumor growth control, especially through modulation of the non-canonical functions of telomerase. On the other hand, long-term exposure to the inhibitor had the potential to induce cell adaptations with possible negative clinical implications.

‘Synthetic cannabis’: A dangerous misnomer

The term 'synthetic cannabis' has been widely used in public discourse to refer to a group of cannabinoid receptor agonists. In this paper we detail the characteristics of these drugs, and present the case that the term is a misnomer. We describe the pharmacodynamics of these drugs, their epidemiology, mechanisms of action, physiological effects and how these differ substantially from delta-9-tetrahydrocannabinol (THC). We argue that not only is the term a misnomer, but it is one with negative clinical and public health implications. Rather, the substances referred to as 'synthetic cannabis' in public discourse should instead be referred to consistently as synthetic cannabinoid receptor agonists (SCRAs), a drug class distinct from plant-derived cannabinoids. SCRAs have greater potency and efficacy, and psychostimulant-like properties. While such terminology may be used in the scientific community, it is not widely used amongst the media, general public, people who use these drugs or may potentially do so. A new terminology has the potential to reduce the confusion and harms that result from the misnomer 'synthetic cannabis'. The constant evolution of this distinct drug class necessitates a range of distinct policy responses relating to terminology, harm reduction, epidemiology, treatment, and legal status.

Chloride sensing by WNK1 regulates NLRP3 inflammasome activation and pyroptosis

The NLRP3 inflammasome mediates the production of proinflammatory cytokines and initiates inflammatory cell death. Although NLRP3 is essential for innate immunity, aberrant NLRP3 inflammasome activation contributes to a wide variety of inflammatory diseases. Understanding the pathways that control NLRP3 activation will help develop strategies to treat these diseases. Here we identify WNK1 as a negative regulator of the NLRP3 inflammasome. Macrophages deficient in WNK1 protein or kinase activity have increased NLRP3 activation and pyroptosis compared with control macrophages. Mice with conditional knockout of WNK1 in macrophages have increased IL-1β production in response to NLRP3 stimulation compared with control mice. Mechanistically, WNK1 tempers NLRP3 activation by balancing intracellular Cl– and K+ concentrations during NLRP3 activation. Collectively, this work shows that the WNK1 pathway has a critical function in suppressing NLRP3 activation and suggests that pharmacological inhibition of this pathway to treat hypertension might have negative clinical implications.

Additional distal femoral resection increases mid-flexion coronal laxity in posterior-stabilized total knee arthroplasty with flexion contracture : a computational study.

Surgeons commonly resect additional distal femur during primary total knee arthroplasty (TKA) to correct a flexion contracture, which leads to femoral joint line elevation. There is a paucity of data describing the effect of joint line elevation on mid-flexion stability and knee kinematics. Thus, the goal of this study was to quantify the effect of joint line elevation on mid-flexion laxity. Six computational knee models with cadaver-specific capsular and collateral ligament properties were implanted with a posterior-stabilized (PS) TKA. A 10° flexion contracture was created in each model to simulate a capsular contracture. Distal femoral resections of + 2 mm and + 4 mm were then simulated for each knee. The knee models were then extended under a standard moment. Subsequently, varus and valgus moments of 10 Nm were applied as the knee was flexed from 0° to 90° at baseline and repeated after each of the two distal resections. Coronal laxity (the sum of varus and valgus angulation with respective maximum moments) was measured throughout flexion. With + 2 mm resection at 30° and 45° of flexion, mean coronal laxity increased by a mean of 3.1° (SD 0.18°) (p < 0.001) and 2.7° (SD 0.30°) (p < 0.001), respectively. With + 4 mm resection at 30° and 45° of flexion, mean coronal laxity increased by 6.5° (SD 0.56°) (p < 0.001) and 5.5° (SD 0.72°) (p < 0.001), respectively. Maximum increased coronal laxity for a + 4 mm resection occurred at a mean 15.7° (11° to 33°) of flexion with a mean increase of 7.8° (SD 0.2°) from baseline. With joint line elevation in primary PS TKA, coronal laxity peaks early (about 16°) with a maximum laxity of 8°. Surgeons should restore the joint line if possible; however, if joint line elevation is necessary, we recommend assessment of coronal laxity at 15° to 30° of knee flexion to assess for mid-flexion instability. Further in vivo studies are warranted to understand if this mid-flexion coronal laxity has negative clinical implications. Cite this article: Bone Joint J2021;103-B(6 Supple A):87-93.

Histological findings of totally embedded robot assisted laparoscopic radical prostatectomy (RALP) specimens in 1197 men with a negative (low risk) preoperative multiparametric magnetic resonance imaging (mpMRI) prostate lobe and clinical implications.

Prostate multiparametric magnetic resonance imaging (mpMRI) has become a popular initial investigation of an elevated PSA and is being incorporated into active surveillance protocols. Decisions on prostate cancer investigation and management based solely on a normal mpMRI remains controversial. Histopathological findings of a totally embedded normal mpMRI lobe are rarely described. A retrospective review of the histological findings of negative preoperative mpMRI lobes in men treated by robot assisted laparoscopic radical prostatectomy (RALP). Inclusion criteria included a preoperative low risk mpMRI for both lobes (Prostate Imaging-Reporting and Data System (PIRADS) ≤ 2) or one negative lobe (with a PIRADS 3-5 in the opposite lobe). A single normal mpMRI lobe was identified in 1018 men (PIRADS 3-5 group). Both lobes were normal in 179 men (PIRADS ≤ 2 group). Prostate cancer was identified in 47.6% (485/1018) of the normal mpMRI lobe opposite a PIRADS 3-5 lesion, including 13.2% (134/1018) with >0.5 cc of International Society of Urologic Pathologists (ISUP) grade 2, or a higher grade cancer. ISUP grade 4-5 was only identified in 2% (20/1018). Compared to RALP histology of the PIRADS 3-5 mpMRI tumour, a pathological ISUP upgrade in the normal mpMRI lobe was identified in 58/1018 men (5.7%). In the PIRADS ≤ 2 group extraprostatic extension occurred in 19% (34/179) and seminal vesicle invasion (pT3b) in 3.9% (7/179). There was no difference in margin status between the PIRADS 3-5 and ≤2 groups (p = 0.247). mpMRI underestimates tumour grade and volume compared to totally embedded histopathological analysis of RALP specimens, although ISUP grade 4-5 cancer is uncommon. Our analysis provides useful insight into the multifocality of prostate cancers, and highlights the utility of systematic biopsy, in addition to targeted biopsies. These results have ramifications for clinical decisions on prostate cancer management based solely on the mpMRI appearance, including active surveillance.

Low-temperature degradation increases the cyclic fatigue resistance of 3Y-TZP in bending

ObjectiveDue to past failures of orthopedic 3Y-TZP femoral implants linked to accelerated tetragonal-to-monoclinic phase transformation (t → m), the susceptibility to ‘low-temperature degradation’ or ‘ageing’ of 3Y-TZP has been advertised as detrimental to its long-term structural stability. However, no systematic mechanistic experiments on the fatigue resistance of aged 3Y-TZP under cyclic loading can support such statement. In this study, we aim to clarify this issue. MethodsHere we evaluate the subcritical crack growth behavior of 3Y-TZP under cyclic loading after 0–50 h of accelerated ageing in an autoclave at 134 °C. The same 3Y-TZP sintered at two different temperatures (1450 °C or 1650 °C) allows for the comparison of materials containing grains with different susceptibilities to transformation. The volume fraction of surface transformed grains was measured using Raman spectroscopy, and the depth of the transformed surface layer from trenches milled with a Focus-Ion Beam. The fracture toughness before and after ageing was determined using the Chevron-notch Beam method. The quasi-static flexural strength was measured in dry conditions and the cyclic lifetime in water at 10 Hz and R-ratio = 0.3 in 4-point-bending at different applied stresses. The fatigue parameter n was derived from 3 different methods, namely SN curves, crack velocity plots and Weibull distributions. ResultsThe progression of transformation showed linear kinetics with higher rates for the 3Y-TZP sintered at 1650 °C. Accelerated transformation induced severe crack formation within the transformed layer with parallel orientation to the surface plane, which supposedly behaved as the critical crack size population governing fracture. The stress intensity factor within the transformed layer was increased due to compressive stresses. Consequently, the fatigue parameter n increased consistently from 5 to 50 h of ageing, regardless of the derivation method, suggesting an increased resistance against crack growth during cyclic loading in bending. SignificanceOur results do not support the long suggested negative clinical implications of LTD regarding mechanical performance, to the contrary, LTD seems to increase the resistance against subcritical crack growth in a humid environment in bending.

Factors Associated With Caregiver-Child Symptom Concordance Among Trauma-Exposed Children.

Concordance in caregivers' and children's reports of children's trauma-related symptoms is often low, and symptom discrepancies are associated with negative clinical implications. The aim of the current study was to examine the degree of concordance between children's and caregivers' reports of trauma-related difficulties and determine whether any child or family characteristics were associated with symptom agreement. Three hundred thirteen trauma-exposed children (M = 9.55, SD = 1.77; 65.2% girls, 51.3% Black) and their nonoffending caregivers seeking treatment were included in the study. Children's and caregivers' reports of trauma-related difficulties were related, but low intraclass correlation coefficients indicated poor concordance across symptoms. Child's gender was associated with levels of concordance for several trauma-related difficulties (e.g., anxiety, depression, anger, dissociation, and sexual concerns), with lower symptom agreement for girls. Child's age, minority status, and relationship to caregiver emerged as factors related to levels of concordance for certain trauma-related symptoms. Child's gender, age, minority status, and relationship to caregiver may predict symptom discordance for select trauma-related difficulties, whereas other family factors such as caregiver marital status and income may be unrelated. Given the importance of caregiver-child concordance in treatment success, additional research should investigate other factors that may influence trauma-related symptom agreement.

Derivation and validation of a model predicting the likelihood of vaginal birth following labour induction

BackgroundThere is high-quality evidence supporting induction of labour (IOL) for a number of maternal and fetal indications. However, one fifth of inductions fail to result in vaginal births, requiring cesarean deliveries. This has negative clinical, emotional and resource implications. The importance of predicting the success of labour induction to enable shared decision-making has been recognized, but existing models are limited in scope and generalizability. Our objective was to derive and internally validate a clinical prediction model that uses variables readily accessible through maternal demographic data, antenatal history, and cervical examination to predict the likelihood of vaginal birth following IOL.MethodsData was extracted from electronic medical records of consecutive pregnant women who were induced between April and December 2016, at Mount Sinai Hospital, Toronto, Canada. A multivariable logistic regression model was developed using 16 readily accessible variables identified through literature review and expert opinion, as predictors of vaginal birth after IOL. The final model was internally validated using 10-fold cross-validation.ResultsOf the 1123 cases of IOL, 290 (25.8%) resulted in a cesarean delivery. The multivariable logistic regression model found maternal age, parity, pre-pregnancy body mass index and weight, weight at delivery, and cervical dilation at time of induction as significant predictors of vaginal delivery following IOL. The prediction model was well calibrated (Hosmer-Lemeshow χ2 = 5.02, p = 0.76) and demonstrated good discriminatory ability (area under the receiver operating characteristic (AUROC) curve, 0.81 (95% CI 0.78 to 0.83)). Finally, the model showed good internal validity [AUROC 0.77 (95% CI 0.73 to 0.82)].ConclusionsWe have derived and internally validated a well-performing clinical prediction model for IOL in a large and diverse population using variables readily accessible through maternal demographic data, antenatal history, and cervical examination. Once prospectively validated in diverse settings, and if shown to be acceptable to pregnant women and healthcare providers as well as clinically and cost-effective, this model has potential for widespread use in clinical practice and research for enhancing patient autonomy, improving induction outcomes, and optimizing allocation of resources.

International Group for Reducing Inappropriate Medication Use & Polypharmacy (IGRIMUP): Position Statement and 10 Recommendations for Action.

Globally, the number of drug prescriptions is increasing causing more adverse drug events, which is now a significant cause of mortality, morbidity, and disability that has reached epidemic proportions. The risk of adverse drug events is correlated to very old age, multiple co-morbidities, dementia, frailty, and limited life expectancy, with the major contributor being polypharmacy. Each characteristic alters the risk–benefit balance of medications, typically reducing anticipated benefits and amplifying risk. Current clinical guidelines are based on evidence proven in younger/healthier adult populations using a single disease model and their application to older adults with multimorbidity, in whom testing has not been conducted, yields a different risk–benefit prospect and makes inappropriate medication use and polypharmacy inevitable. Applying inappropriate clinical practice guidelines to older adults is antithetical to good healthcare, is likely to increase health inequity, and is associated with substantial negative clinical, economic, and social implications for health systems. The casualties are on the scale of a war or epidemic, yet are usually invisible in measures of healthcare quality and formal recommendations. Radical and rapid action is required to achieve a better quality of life for older populations and to remain true to the principles of medical professionalism and evidence-based medicine that place patients’ interests and autonomy at the fore. This first International Group for Reducing Inappropriate Medication Use & Polypharmacy position statement briefly details the causes, consequences, and extent of inappropriate medication use and polypharmacy. This article outlines current strategies to reduce inappropriate medication use, provides evidence for their effect, and then proposes recommendations for moving forward with 10 recommendations for action and 12 recommendations for research. We conclude that an urgent integrated effort to reduce inappropriate medication use and polypharmacy should be a leading global target of the highest priority. The cornerstone of this position statement from the International Group for Reducing Inappropriate Medication Use & Polypharmacy is the understanding that without evidence of definite relevant benefit, when it comes to prescribing, for many older patients ‘less is more’. This approach differs from most other current recommendations and guidance in medical care, as the focus is on what, when, and how to stop, rather than on when to start medications/interventions. Disrupting the framework that indiscriminately applies standard guidelines to older adults requires a new approach that better serves patients with multimorbidity. This transition requires a shift in medical education, research, and diagnostic frameworks, and re-examination of the measures used as quality indicators. In achieving this objective, we promote a return to some of the original concepts of evidence-based medicine: which considers scientific data (where it exists), clinical judgment, patient/family preference, and context. A shift is needed: from the current model that focuses on single conditions to one that simultaneously considers multiple conditions and patient priorities. This approach reframes the clinician’s role as a professional providing care, rather than a disease technician.

Deriving a Clinical Prediction Tool to Measure the Success of Labour Induction [12OP

INTRODUCTION: There is high-quality evidence supporting induction of labour (IOL) for a number of maternal and fetal indications. However, one fifth of inductions fail, requiring emergency cesarean deliveries. This has negative clinical, emotional and financial implications. Our objective was to derive and internally validate a clinical prediction tool to determine the success of IOL. METHODS: Data was extracted from electronic medical records of consecutive pregnant women who were induced between April 26, 2016 and December 31, 2016, at Mount Sinai Hospital (Toronto, Canada). A multivariable logistic regression model was developed using variables identified as predictors of successful IOL by literature review and expert opinion. Repeated K-fold cross-validation was used to internally validate the model. RESULTS: Of the 916 cases of IOL, 249 (27%) failed. The multivariable logistic regression model found maternal age, parity, pre-pregnancy weight, pre-pregnancy body mass index, weight at delivery and cervical dilation at time of induction as significant predictors of successful IOL. The prediction tool was well calibrated (Hosmer-Lemeshow χ2=6.42, P=.60) and demonstrated good discriminatory ability (area under the receiver-operating characteristic curve [AUROC], 0.79 [95% CI 0.76–0.82]). Internal validation of the model showed a similar discriminatory ability (AUROC, 0.77 [95% CI 0.68–0.85). CONCLUSION: We have derived and internally validated a clinical prediction tool for IOL in a large and diverse population. Once prospectively validated in other settings, this has potential for widespread use in clinical practice and research, as well as for enhancing patient experience and allocation of healthcare resources.

Validation of Peripheral Quantitative Computed Tomography–Derived Thigh Adipose Tissue Subcompartments in Young Girls Using a 3 T MRI Scanner

The ability to assess skeletal muscle adipose tissue is important given the negative clinical implications associated with greater fat infiltration of the muscle. Computed tomography and magnetic resonance imaging (MRI) are highly accurate for measuring appendicular soft tissue and muscle composition, but have limitations. Peripheral quantitative computed tomography (pQCT) is an alternative that investigators find valuable because of its low radiation, fast scan time, and comparatively lower costs. The present investigation sought to assess the accuracy of pQCT-derived estimates of total, subcutaneous, skeletal muscle, intermuscular, and calculated intramuscular adipose tissue areas, and muscle density in the midthigh of young girls using the gold standard, 3 T MRI, as the criterion. Cross-sectional data were analyzed for 26 healthy girls aged 9–12 years. Midthigh soft tissue composition was assessed by both pQCT and 3 T MRI. Mean tissue area for corresponding adipose compartments by pQCT and MRI was compared using t tests, regression analysis, and Bland-Altman plots. Muscle density was regressed on MRI skeletal muscle adipose tissue, intermuscular adipose tissue, and intramuscular adipose tissue, each expressed as a percentage of total muscle area. Correlations were high between MRI and pQCT for total adipose tissue (r2 = 0.98), subcutaneous adipose tissue (r2 = 0.95), skeletal muscle adipose tissue (r2 = 0.83), and intermuscular adipose tissue (r2 = 0.82), and pQCT muscle density correlated well with both MRI skeletal muscle adipose tissue (r2 = 0.70) and MRI intermuscular adipose tissue (r2 = 0.70). There was a slight, but statistically significant underestimation by pQCT for total and subcutaneous adipose tissue, whereas no significant difference was observed for skeletal muscle adipose tissue. Both pQCT-estimated intramuscular adipose tissue and muscle density were weakly correlated with MRI-intramuscular adipose tissue. We conclude that pQCT is a valid measurement technique for estimating all adipose subcompartments, except for intramuscular adipose tissue, for the midthigh region in young/adolescent girls.

Cross-cultural psychometric assessment of the VAGUS insight into psychosis scale – Spanish version

Impaired insight into illness, a core feature of schizophrenia with negative clinical implications, is a multidimensional phenomenon existing on a continuum. However, the degree to which illness perception in distinct cultures influences the appraisal of insight into illness in schizophrenia remains unclear. As such, we aimed to determine if the psychometric properties of the VAGUS insight into psychosis scale (www.vagusonline.com), which was originally assessed in English speaking Canadians, were similar in a sample of Latino Mexican Spanish speaking patients with schizophrenia. To accomplish this, the VAGUS – Self-Report (SR) version was translated from English to Spanish and psychometrically evaluated in 95 participants. The Spanish version of the VAGUS-SR was internally consistent (ᾳ = 0.713), and demonstrated good convergent and discriminant validity with the subscales of the Positive and Negative Syndrome Scale. Factor analysis identified two components of insight, congruent with two of the components of the English version of the VAGUS-SR. In conclusion, the VAGUS-SR is a brief, novel, and valid measure of insight into illness in schizophrenia, which demonstrated similar psychometric properties in two culturally and linguistically distinct samples with schizophrenia. Future studies should assess whether the VAGUS demonstrates similar psychometric properties in non-Western cultures.

Novel prognostic molecular factors: a quantum leap in the field of chronic lymphocytic leukemia

Cytogenetic lesions do not completely explain clinical heterogeneity of chronic lymphocytic leukemia (CLL). The 2016 revision of the World Health Organization classification 2008 indicated that molecular lesions of TP53, NOTCH1, SF3B1 and BIRC3 have potential clinical relevance and could be integrated into an updated risk profile. The negative clinical implications of TP53 disruptions are well constituted and patients with these mutations should be considered for novel, small molecule signal transduction inhibitors therapies. Mutations of NOTCH1, SF3B1 and BIRC3 are associated with poor prognosis. Patients with mutated SF3B1 or NOTCH1 genes present shorter time to first treatment compared to unmutated group. NOTCH1 mutations are related to a high risk of Richter's syndrome transformation, especially in case of TP53 disruptions' coexistence. Large studies on MYD88 mutations in CLL have not explained clearly their clinical importance.The aim of this paper is to provide a comprehensive review on novel molecular aberrations identified in CLL.