Post-traumatic stress disorder and childhood emotional abuse are markers of subthreshold bipolarity and worse treatment outcome in major depressive disorder

Post-traumatic stress disorder (PTSD) and childhood maltreatment (CMT: Parental neglect; emotional, physical and sexual abuse) have been linked to bipolar disorder but they are also common in major depressive disorder (MDD). Our objective was to investigate their association with the bipolar spectrum and antidepressant treatment outcome in 482 outpatients with DSM-IV MDD treated in the Combining Medications to Enhance Depression Outcomes trial for 28 weeks Bipolar spectrum score included age of onset <21 years, subthreshold hypomania (a period of elated or irritable mood with at least two concurrent hypomanic symptoms, which did not fulfill DSM criteria for hypomanic/manic episode) and depressive mixed state (DMX). PTSD subjects (n = 107; 22%) had more severe depression (P < 0.0001), work and social impairment (P = 0.0031), comorbid anxiety disorders (P < 0.0001) and increased suicidality (P = 0.0003). Bipolar spectrum score was higher with PTSD comorbidity (P = 0.0063) and childhood emotional abuse (P = 0.0001). PTSD comorbidity was associated with residual suicidality (P = 0.0218) after 6 weeks of antidepressant use whereas childhood emotional abuse [odds ratio (OR), 1.01-2.22], subthreshold hypomania (OR, 1.04-4.09) and DMX (OR, 1.00-4.19) were predictors of mood switch. These results corroborate the role of PTSD and childhood emotional abuse as markers of bipolar spectrum and prognostic factors during antidepressant treatment

Persistence of suicidal ideation within acute phase treatment of major depressive disorder: Analysis of clinical predictors

Suicidal ideation (SI) is common in major depressive disorder (MDD), and it is a risk factor for suicidal behaviour. Antidepressants are effective in reducing SI, but in some subjects, SI may persist for weeks. This study aimed to disentangle the contribution of baseline clinical characteristics in SI nonremission at week 6. Research involved 198 outpatients with MDD and SI collected within the Combining Medications to Enhance Depression Outcomes trial and treated with different antidepressant combinations. Although SI decreased from baseline to week 6 (P < 0.0001), 78 patients (39%) failed to achieve SI remission. Insomnia [OR, 0.72; 95% confidence interval (CI), 0.52-0.99], reduced need for sleep (OR, 0.75; 95% CI, 0.58-0.99), self-confidence (OR, 0.52; 95% CI, 0.32-0.82), cheerfulness (OR, 0.57; 95% CI, 0.33-0.98), and comorbid panic disorder (OR, 0.93; 95% CI, 0.87-0.99) at baseline were associated with lack of SI remission after controlling for baseline depression and SI scores. The combination of baseline SI and insomnia was moderately effective in predicting the lack of SI remission, with a specificity of 80% (95% CI, 72-87%) and an NPV of 68% (95% CI, 63-72%). In individuals with MDD and SI, the presence of insomnia and bipolar features should prompt a search for more effective treatment solutions in order to favour SI remission and prevent suicidal behaviour

Patient-Centered Outcomes of Microfragmented Adipose Tissue Treatments of Knee Osteoarthritis: An Observational, Intention-to-Treat Study at Twelve Months

© 2020 Nima Heidari et al. Introduction. Microfragmented adipose tissue (MFAT) has been shown to benefit osteoarthritic patients by reducing pain and supporting tissue regeneration through a mesenchymal stem cell (MSC)-related paracrine mechanism. This observational study of 110 knees assessed patient-centered outcomes of pain, functionality, and quality of life, analyzing their variation at twelve months following one ultrasound-guided intra-articular injection of autologous MFAT for the treatment of knee osteoarthritis (KOA). Method. Inclusion criteria were as follows: VAS >50, and the presence of KOA as diagnosed on X-ray and MRI. Exclusion criteria included the following: recent injury (<3 months) of the symptomatic knee, intra-articular steroid injections performed within the last three months, and hyaluronic acid injections prior to this treatment. Changes in VAS, OKS, and EQ-5D were scored at baseline and twelve months following a single intra-articular injection of autologous MFAT. Score variation was analyzed utilizing a nonparametric paired samples Wilcoxon test. The statistical analysis is reproducible with Open Access statistical software R (version 4.0.0 or higher). The study was carried out with full patient consent, in a private practice setting. Results. Median VAS (pain) improved from 70 (IQR 20) to 30 (IQR 58) (p<0.001); median OKS (function) improved from 25 (IQR 11) to 33.5 (IQR 16) (p<0.001); and median EQ-5D (quality of life) improved from 0.62 (IQR 0.41) to 0.69 (IQR 0.28) (p<0.001). No adverse events were reported during the intraoperative, recovery, or postoperative periods. Conclusions. For patients with all grades of knee osteoarthritis who were treated with intra-articular injections of MFAT, statistically significant improvements in pain, function, and quality of life were reported. Although further research is warranted, the results are encouraging and suggest a positive role for intra-articular injection of MFAT as a treatment for knee osteoarthritis

Comparison of the effect of MFAT and MFAT + PRP on treatment of hip osteoarthritis : an observational, intention-to-treat study at one year

Hip osteoarthritis (OA) is a major contributor to reduced quality of life and concomitant disability associated with lost working life months. Intra-articular injection of various biological materials has shown promise in alleviating symptoms and potentially slowing down the degenerative process. Here, we compared the effects of treatment of a cohort of 147 patients suffering from grade 1–4 hip OA; with either micro-fragmented adipose tissue (MFAT), or a combination of MFAT with platelet-rich plasma (PRP). We found significant improvements in both the visual analogue score for pain (VAS) and Oxford hip score (OHS) that were similar for both treatments with over 60% having an improvement in the VAS score of 20 points or more. These results suggest a positive role for intra-articular injection of MFAT + PRP as a treatment for hip osteoarthritis which may be important particularly in low body mass index (BMI) patients where the difficulty in obtaining sufficient MFAT for treatment could be offset by using this combination of biologicals

Gender-specific response in pain and function to biologic treatment of knee osteoarthritis : a gender-bias-mitigated, observational, intention-to-treat study at two years

Knee osteoarthritis is a major cause of disability worldwide. Newer modalities of treatment with less morbidity, such as intra-articular injection of microfragmented fat (MFAT), are showing promise. We report on our novel observation that women show a greater improvement in pain and function to MFAT than men. Traditionally, women have been underrepresented in studies and studies with both sexes regularly fail to analyze the results by sex. To mitigate for this bias and quantify it, we describe a technique using reproducible statistical analysis and replicable results with Open Access statistical software R to calculate the magnitude of this difference. Genetic, hormonal, environmental, and age factors play a role in our observed difference between the sexes. There is a need for further studies to identify the molecular basis for this difference and be able to utilize it to improve outcome for both women and men

Microfragmented Adipose Tissue Injection (MFAT) may be a solution to the rationing of total knee replacement : a prospective, gender-bias mitigated, reproducible analysis at two years

Background. Knee osteoarthritis (KOA) is a significant cause of disability in a globally ageing population. Knee replacement surgery has been shown to improve function and quality of life. Access to this intervention can be limited for a number of reasons including rationing of care, lack of healthcare provision in austere environments, and more recently, due to the cessation of elective orthopaedic care as a result of the COVID pandemic. Referral for knee replacement surgery is often guided by the patient's Oxford Knee Score (OKS). Recent therapies including treatment with microfragmented adipose tissue (MFAT) have emerged as alternatives to relieve pain and improve function in such patients. Method. We identified all patients with KOA Kellgren-Lawrence grade 3 and 4 in our dataset of patients treated with a single injection of MFAT and applied published OKS thresholds for referral for TKR to separate them into 3 cohorts according to their functional impairment. 220 patients (95 females, 125 males) with KOA were given one MFAT injection. The function (OKS) and quality of life (EuroQol-5) prior to and 24 months after therapy were compared. Results. MFAT injection provided a statistically significant improvement in the quality of life (EQ-5D) at 24 months in patients with a baseline OKS of 39 or less (p value: <0.001) as well as those with OKS of 27 or less who are deemed suitable for a knee replacement (p value: <0.001). Conclusion. MFAT injection improves quality of life in patients with KOA who are deemed suitable for the knee replacement. MFAT is a low-morbidity alternative biological treatment and can delay the need for total knee replacement in suitable patients

ETS exposure and PAH body burden in nonsmoking Italian adults

Active smoking is associated with increased body burden of polycyclic aromatic hydrocarbons (PAHs); the aim of this study was to assess whether environmental tobacco smoking (ETS) increases the internal dose of PAHs. In 344 nonsmoking Italian adults, out of 497 individuals selected as representative of the population of the town of Modena, ETS exposure was evaluated by a self-administered questionnaire and by the measurement of urinary cotinine (COT-U). PAH exposure was assessed by the measurement of urinary 1-hydroxypyrene (1-OHPYR) and of ten urinary PAHs. In all subjects, median (5th-95th percentile) COT-U was 0.47 (<0.1-3.91) mu g/L. While 58 subjects reported to be ETS exposed (ETSQUEST), 38 individuals were identified as ETS exposed on the basis of a COT-U value of 1.78 (90% confidence interval 1.75-1.80) mu g/L, previously derived as an upper reference value in not ETS exposed Italian adults (ETSCOT). Median COT-U levels were 1.38 (<0.1-9.06) and 3.63 (1.80-17.39) mu g/L in ETSQUEST and in ETSCOT subjects, respectively. Significant correlations between COT-U and 1-OHPYR, and urinary anthracene, fluoranthene, pyrene, and chrysene were found among all subjects. Significantly higher levels of 1-OHPYR, and urinary fluorene, anthracene, and pyrene were found in ETSCOT individuals. The results of multiple linear regression analyses, taking into consideration diet and other sources of PAHs exposures such as the residence area/characteristics and traffic, confirmed that 1-OHPYR and urinary fluorene were affected by ETS exposure, even if ETS played a minor role

Aqueous Stable Gold Nanostar/ZIF‐8 Nanocomposites for Light‐Triggered Release of Active Cargo Inside Living Cells

This is the peer reviewed version of the following article: C. Carrillo-Carrión, R. Martínez, M. F. Navarro Poupard, B. Pelaz, E. Polo, A. Arenas-Vivo, A. Olgiati, P. Taboada, M. G. Soliman, Ú. Catalán, S. Fernández-Castillejo, R. Solà, W. J. Parak, P. Horcajada, R. A. Alvarez-Puebla, P. del Pino, Angew. Chem. Int. Ed. 2019, 58, 7078, which has been published in final form at https:// doi.org/10.1002/anie.201902817. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsA plasmonic core–shell gold nanostar/zeolitic‐imidazolate‐framework‐8 (ZIF‐8) nanocomposite was developed for the thermoplasmonic‐driven release of encapsulated active molecules inside living cells. The nanocomposites were loaded, as a proof of concept, with bisbenzimide molecules as functional cargo and wrapped with an amphiphilic polymer that prevents ZIF‐8 degradation and bisbenzimide leaking in aqueous media or inside living cells. The demonstrated molecule‐release mechanism relies on the use of near‐IR light coupled to the plasmonic absorption of the core gold nanostars, which creates local temperature gradients and thus, bisbenzimide thermodiffusion. Confocal microscopy and surface‐enhanced Raman spectroscopy (SERS) were used to demonstrate bisbenzimide loading/leaking and near‐IR‐triggered cargo release inside cells, thereby leading to DNA stainingThis work has received financial support from the MINECO‐Spain (MAT2016‐80266‐R, MAT2015‐74381‐JIN, CTQ2017‐88648R, ENE2016‐79608‐C2‐1‐R, CTQ2017‐89588‐R, RYC‐2014‐15039, RYC‐2014‐16962), the Xunta de Galicia, Centro singular de investigación de Galicia accreditation 2016–2019 (ED431G/09), the Agrupación Estratégica de Materiales Action (ED431E 2018/08), the Generalitat de Cataluña (2017SGR522, 2017SGR883, SLT002/16/00239), the URV (2017PFR‐URV‐B2‐02), the German Research Society (DFG PA 794‐21‐1), and the European Union (European Regional Development Fund—ERDF, H2020‐MSCA‐IF‐2016, project 749667). M.F.N.P acknowledges the CONACYT PhD fellowship programS