A Mixed-Methods Systematic Review on Syndemics in Rheumatology.

OBJECTIVE: We aimed to assess the use of framework and corresponding methodology to document syndemics and its impact in rheumatic and musculoskeletal diseases (RMDs). METHODS: Using a mixed-methods systematic review, studies using the syndemic framework approach for RMDs were identified and published from January 2003 to January 2021. The Joanna Briggs Institute, Cochrane Collaboration, and PRISMA guidelines were followed to search, retrieve, revise, and analyze. RESULTS: A total of 658 potential articles were identified, but only 10 were initially eligible. After a full-text review, 4 were included. Following a full-text review, 2 quantitative, 1 qualitative, and 1 mixed-methods study were included. In the first, network analysis found that RMDs were associated with comorbidities, unhealthy habits, low educational level, living in rural areas, socioeconomic conditions, and health inequality in indigenous communities. In the second, SSEM and cluster analysis demonstrated an association between low back pain and factors, such as comorbidities and indigenous status, among others, in urban/rural communities. The qualitative study examined 3 fishing family generations and reported less syndemic vulnerability. The mixed-methods study focused on osteoarthritis with multimorbidities in African American population, where lack of education added to worsening outcomes. CONCLUSIONS: Even though the insights syndemic studies have given to other areas, its use in rheumatology is scarce. The complexity of the clinical and social determinants related to RMDs makes it necessary to conduct further studies from a syndemic perspective.

Participation of angiotensin-(1-7) in exercise-induced analgesia in rats with neuropathic pain.

Exercise reduces neuropathic pain in animals and humans. Recent studies indicate that training exercise favors the synthesis and action of angiotensin-(1-7) (Ang-(1-7)), a vasoactive peptide of the renin-angiotensin system (RAS), in various tissues. Interestingly, Ang-(1-7) also relieves neuropathic pain; however, it remains to be elucidated whether exercise mitigates this type of pain through Ang-(1-7). In this study, we investigated the role of Ang-(1-7) in exercise-induced analgesia in a neuropathic pain model. Male Wistar rats were ligated of lumbar spinal nerves (L5 and L6) or sham-operated. Then, they were subjected to acute (2-h) or chronic (4-week) exercise protocols. Tactile allodynia was evaluated before and after each exercise intervention. Microosmotic pumps were implanted subcutaneously for the release of Ang-(1-7) or A779 (selective Mas receptor (MasR; Ang-(1-7) receptor) antagonist). Plasma levels of Ang II and Ang-(1-7) were quantified by HPLC. Spinal nerve ligation (SNL) produced tactile allodynia. Both acute and chronic exercise reversed this neuropathic behavior. A779 treatment prevented the antiallodynic effect induced by each exercise protocol. SNL increased the plasma Ang II/Ang-(1-7) ratio; however, exercise did not modify it. Acute treatment with Ang-(1-7) via MasR mimicked exercise-mediated antinociception. Collectively, these results suggest that activation of the Ang-(1-7)/MasR axis of the RAS represents a potential novel mechanism by which exercise attenuates neuropathic pain in rats.

Predictors of early mortality in very elderly patients with bacteremia: a prospective multicenter cohort.

OBJECTIVES: The proportion of very elderly people in the population is increasing, and infectious diseases in this patient group may present with specific characteristics. The objective of this study was to investigate the outcome predictors of bacteremia among the very elderly. METHODS: This was a multicenter prospective cohort study of bloodstream infections (BSI) in patients ≥ 80 years old in 15 hospitals in Spain. The outcome variables were 14-day and 30-day mortality. Multivariate analysis was performed. RESULTS: One hundred and twenty episodes were included. Mortality was 22% (n = 26) on day 14 and 28% (n = 34) on day 30. In the univariate analysis, the variables associated with mortality were neutropenia, recent surgery, Pitt score ≥ 2, intensive care unit (ICU) admission, severe sepsis or shock, and abdominal, unknown, and respiratory tract sources. In the multivariate analysis, variables associated with mortality on day 14 were high-risk source (abdominal, unknown, and respiratory tract sources; odds ratio (OR) 7.9, 95% confidence interval (CI) 1.8-33.9), Pitt score ≥ 2 (OR 5.6, 95% CI 1.3-23.3), inadequate empirical treatment (OR 11.24, 95% CI 1.6-80.2), and severe sepsis or shock at presentation (OR 5.3, 95% CI 1.4-20.7); the interaction between empiric treatment and high-risk source was significant. On day 30, mortality was independently related to a high-risk source (OR 2.92, 95% CI 1.1-7.5) and presentation with severe sepsis or shock (OR 3.81, 95% CI 1.2-12.4). CONCLUSIONS: Presentation with severe sepsis or shock and a high-risk source of BSI were independent predictors of 14-day and 30-day mortality. Inadequate empirical treatment was also a predictor of early mortality in patients with a high-risk source.

Reappraisal of the outcome of healthcare-associated and community-acquired bacteramia: a prospective cohort study.

BACKGROUND: Healthcare-associated (HCA) bloodstream infections (BSI) have been associated with worse outcomes, in terms of higher frequencies of antibiotic-resistant microorganisms and inappropriate therapy than strict community-acquired (CA) BSI. Recent changes in the epidemiology of community (CO)-BSI and treatment protocols may have modified this association. The objective of this study was to analyse the etiology, therapy and outcomes for CA and HCA BSI in our area. METHODS: A prospective multicentre cohort including all CO-BSI episodes in adult patients was performed over a 3-month period in 2006-2007. Outcome variables were mortality and inappropriate empirical therapy. Adjusted analyses were performed by logistic regression. RESULTS: 341 episodes of CO-BSI were included in the study. Acquisition was HCA in 56% (192 episodes) of them. Inappropriate empirical therapy was administered in 16.7% (57 episodes). All-cause mortality was 16.4% (56 patients) at day 14 and 20% (71 patients) at day 30. After controlling for age, Charlson index, source, etiology, presentation with severe sepsis or shock and inappropriate empirical treatment, acquisition type was not associated with an increase in 14-day or 30-day mortality. Only an stratified analysis of 14th-day mortality for Gram negatives BSI showed a statically significant difference (7% in CA vs 17% in HCA, p = 0,05). Factors independently related to inadequate empirical treatment in the community were: catheter source, cancer, and previous antimicrobial use; no association with HCA acquisition was found. CONCLUSION: HCA acquisition in our cohort was not a predictor for either inappropriate empirical treatment or increased mortality. These results might reflect recent changes in therapeutic protocols and epidemiological changes in community pathogens. Further studies should focus on recognising CA BSI due to resistant organisms facilitating an early and adequate treatment in patients with CA resistant BSI.

Validation in Spanish of a screening questionnaire for the detection of psoriatic arthritis in patients with psoriasis.

OBJECTIVE: A patient self-administered questionnaire [PsA Screening and Evaluation (PASE)] has been developed and validated in English, but has not been tried in Spanish speaking populations. This study aimed to adapt and validate PASE in Spanish to screen Spanish speaking psoriasis patients for signs and symptoms of inflammatory arthritis. METHODS: Initial translation from English to Spanish (forward translation) was performed by two independent translators and the resulting versions were synthesized during a consensus meeting. The questionnaire was tried in a pilot study and resulted in a change in the agreement scale for a frequency scale with wording adaptation [Spanish PASE (PASE-S)]. RESULTS: One hundred and eleven patients were screened with PASE-S; 25 with PsA (without previous treatments), 23 with psoriasis, 22 with psoriasis and OA and 41 with OA without psoriasis. The diagnosis of psoriasis was performed by a dermatologist, and a rheumatologist determined the diagnosis of PsA or OA. Patients with PsA had statistically significant higher symptoms, function and total PASE-S scores compared with those without PsA. Receiver operator curves showed an area under the curve of 0.79 (95% CI 0.69, 0.89) for the total score. A cut-off value ≥34 showed sensitivity of 76%, and specificity of 74.4% for the diagnosis of PsA. CONCLUSION: The validated PASE questionnaire is a self-administered tool that can be used to screen for PsA among patients with psoriasis in a Spanish speaking population. PASE was able to distinguish between symptoms of PsA and OA.

Development of microsatellite markers for Anadenanthera colubrina var. cebil (Fabaceae), a native tree from South America.

PREMISE OF THE STUDY: Microsatellite primers were developed in the native legume tree Anadenanthera colubrina var. cebil to study the genetic diversity and genetic structure in natural populations in Argentina. METHODS AND RESULTS: Nine microsatellite markers were identified using a genomic library enriched for tandemly repeated motifs, eight of which markers were polymorphic. The polymorphism of these markers was assessed by investigating 20 individuals for fragment polymorphism; three to 13 alleles were observed for each locus. Observed and expected heterozygosities ranged from 0.300 to 1.000 and from 0.463 to 0.900, respectively. CONCLUSIONS: These results confirm that these primers will be useful for investigating the genetic diversity and genetic structure of natural populations of A. colubrina var. cebil in future studies.

Impact of inadequate empirical therapy on the mortality of patients with bloodstream infections: a propensity score-based analysis.

The impact of the adequacy of empirical therapy on outcome for patients with bloodstream infections (BSI) is key for determining whether adequate empirical coverage should be prioritized over other, more conservative approaches. Recent systematic reviews outlined the need for new studies in the field, using improved methodologies. We assessed the impact of inadequate empirical treatment on the mortality of patients with BSI in the present-day context, incorporating recent methodological recommendations. A prospective multicenter cohort including all BSI episodes in adult patients was performed in 15 hospitals in Andalucía, Spain, over a 2-month period in 2006 to 2007. The main outcome variables were 14- and 30-day mortality. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Eight hundred one episodes were included. Inadequate empirical therapy was administered in 199 (24.8%) episodes; mortality at days 14 and 30 was 18.55% and 22.6%, respectively. After controlling for age, Charlson index, Pitt score, neutropenia, source, etiology, and presentation with severe sepsis or shock, inadequate empirical treatment was associated with increased mortality at days 14 and 30 (odds ratios [ORs], 2.12 and 1.56; 95% confidence intervals [95% CI], 1.34 to 3.34 and 1.01 to 2.40, respectively). The adjusted ORs after a propensity score-based matched analysis were 3.03 and 1.70 (95% CI, 1.60 to 5.74 and 0.98 to 2.98, respectively). In conclusion, inadequate empirical therapy is independently associated with increased mortality in patients with BSI. Programs to improve the quality of empirical therapy in patients with suspicion of BSI and optimization of definitive therapy should be implemented.

Incidence of anaphylaxis in hospitalized patients.

BACKGROUND: Only two studies have analyzed the incidence of anaphylaxis during admission to hospital. We have analyzed the incidence of anaphylaxis among hospitalized patients and determined the timing of and risk factors for episodes of anaphylaxis. METHODS: Our study was performed between 1999 and 2005. We used the definition of anaphylaxis of the NIAID-FAAN symposium. Cases of anaphylaxis were extracted from an official database of discharge diagnoses coded according to the International Classification of Diseases, Clinical Modification, Ninth Revision (ICD-9-CM), Sixth Edition. Specific and generic codes related to anaphylaxis were chosen. This strategy revealed 83.3% (95% confidence interval, CI, 47-99%) of all episodes of anaphylaxis in a pilot study. The incidence of episodes of anaphylaxis and the hazard ratios were calculated for the different variables. RESULTS: We observed a crude cumulative incidence of 1.5 episodes of anaphylaxis (95% CI, 0.9-1.9) in 5,000 admissions. The cumulative incidence according to the Standardized European Population was 1.6 cases in 5,000 admissions (95% CI, 0.8-2.3). Cox regression analysis showed that anaphylaxis occurs mainly in young people (0.97; 95% CI, 0.95-0.99) and its incidence differs according to the clinical unit. The Vascular Surgery Unit had the highest incidence rate (hazard ratio 7.7; 95% CI, 2.1-28.6). Males had a lower risk of suffering from anaphylaxis than females (0.5; 95% CI, 0.2-0.9). CONCLUSIONS: Anaphylaxis is a very rare event among hospitalized patients. Female gender, young age and admission to the Vascular Surgery Unit favored the occurrence of episodes of anaphylaxis among hospitalized patients.

Epigenetic therapy of lymphoma using histone deacetylase inhibitors.

In this study, we reviewed epigenetic therapy of lymphomas using histone deacetylase inhibitors (HDACi), a promising new class of antineoplastic agents. Epigenetic therapy, a new therapeutic concept, consists of the use of HDACi and or DNA methyltransferase inhibitors (DNMTi). We conducted a comprehensive review of the literature for antitumour activity of HDACi and its mechanism of action. HDACi modify the expression of several genes related to cancer development, which can result in antineoplastic activity. To elucidate the benefits of HDACi in lymphoma treatment, we discuss the crucial interplay between BCL6, p53 and STAT3. Activated B-cell (ABC) diffuse large cell lymphoma (DLCL) is increasingly being recognised as an unfavourable and frequently therapy-refractory lymphoma. We discuss the fundamental causative role of the STAT3 oncogene in ABC type DLCL. STAT3 can be effectively suppressed by several HDACi, a promising treatment for this difficult subtype of DLCL. On the other hand, various HDACi can repress the germinal-centre B Cell (GCB) type DLCL by virtue of their inhibition of the BCL6 oncogene, usually expressed in this particular subtype. We summarise the results of recent clinical trials with HDACi such as romidepsin, panobinostat, MGCD-0103, entinostat, curcumin, JAK2 inhibitor TG101348, and valproic acid that have shown preliminary activity in recurrent and refractory lymphomas. The unique mechanism of action of HDACi makes them very attractive agents to pursue in combination. Several ongoing trials are already exploring HDACi combinations in various types of cancers. Their role in front-line management remains to be determined.

Aplasia cutis: a propósito de nueve casos / Aplasia cutis: apropos of 9 cases

Se presentan nueve casos de Aplasia Cutis Congénita, uno de ellos con compromiso de tronco, asociado a epilepsia; el resto de los pacientes presentaban lesiones en cuero cabelludo, uno de ellos se hallaba asociado al síndrome uña-rótula-codo. Hacemos referencia a la clínica, histopatología y asociaciones, considerando la etiopatogenia, y su eventual terapéutica

Aplasia cutis: a propósito de nueve casos / Aplasia cutis: apropos of 9 cases

Se presentan nueve casos de Aplasia Cutis Congénita, uno de ellos con compromiso de tronco, asociado a epilepsia; el resto de los pacientes presentaban lesiones en cuero cabelludo, uno de ellos se hallaba asociado al síndrome uña-rótula-codo. Hacemos referencia a la clínica, histopatología y asociaciones, considerando la etiopatogenia, y su eventual terapéutica (AU)