Beyond the patella: Treatment of cam femoroacetabular impingement syndrome improves anterior knee pain.

OBJECTIVES: This study aimed to investigate if there is a relationship between cam femoroacetabular impingement syndrome (cam-FAIS) and chronic anterior knee pain (AKP). METHODS: This is a pilot retrospective review of 12 AKP patients with no structural anomalies in the patellofemoral joint and no skeletal malalignment in the lower limbs. All the patients were resistant to proper conservative treatment for AKP (AKP-R). Subsequently, these patients developed pain in the ipsilateral hip several months later, and upon evaluation, were diagnosed with cam-FAIS. Arthroscopic femoral osteoplasty and labral repair were performed and clinical follow-up of hip and knee pain and function (Kujala Score and Non-arthritic Hip Score -NAHS-) was carried out. RESULTS: All the patients showed improvement in the knee and hip pain scores with a statistically significant clinical difference in all of them at 69 months follow up (range: 18 to 115) except one patient without improvement in the groin VAS score post-operatively. Visual analogical scale (VAS) of knee pain improved from 6.3 (range: 5 to 8) to a postoperative 0.5 (range: 0 to 3.5), (p â€‹< â€‹0.001). The VAS of groin pain improved from 4.4 (range: 2 to 8) to a postoperative 0.9 (range: 0 to 3), (p â€‹< â€‹0.001). NAHS improved from a preoperative 67.9 (range: 28.7 to 100) to a postoperative 88 (range: 70 to 100), (p â€‹< â€‹0.015) and knee Kujala's score improved from a preoperative 48.7 (range: 22 to 71) to a postoperative 96 (range: 91 to 100), (p â€‹< â€‹0.001). CONCLUSION: This study's principal finding suggests an association between cam-FAIS and AKP-R in young patients who exhibit normal knee imaging and lower limbs skeletal alignment. Addressing cam-FAIS in these cases leads to resolution of both groin and knee pain, resulting in improved functional outcomes for both joints. STUDY DESIGN: Retrospective cohort series with a single contemporaneous long-term follow-up. LEVEL OF EVIDENCE: IV.

Dispensation of outpatient hospital medicines by hospital only versus hospital-community pharmacies collaboration: a cross-sectional study and survey of patient's satisfaction.

Goal: To describe the experience of a dispensing model of outpatient hospital medicines (OHM) via collaboration of hospital and community pharmacies, and to explore patient satisfaction with the strategy as compared with the hospital pharmacy only service. Background: Patient satisfaction is an important component of the quality of health care. Study: A new model of dispensing OHM was conducted in the Outpatients Unit of the Service of Hospital Pharmacy of Hospital del Mar, in Barcelona, Spain. Participants were patients on stable chronic treatment with clinical or social fragility, immunocompromised patients, and those whose residence was located at a distance from the hospital that justified drug delivery through the community pharmacy. A cross sectional study was done using an ad hoc 14-item questionnaire collecting demographic data, duration of treatment, usual mode of collecting medication, and the degree of satisfaction regarding waiting time for the collection of medication, attention received by professionals, information received on treatment, and confidentiality. Results: The study population included a total of 4,057 patients (66.8% men) with a mean age of 53 (15.5) years, of whom 1,286 responded, with a response rate of 31.7%. Variables significantly associated with response to the survey were age over 44 years, particularly the age segment of 55-64 years (odds ratio [OR] 2.51) and receiving OHM via the community pharmacy (OR 12.76). Patients in the community pharmacy group (n = 927) as compared with those in the hospital pharmacy group (n = 359) showed significantly higher percentages of 'satisfied' and 'very satisfied' (p < 0.001) in the waiting time for the collection of OHM (88.1% vs. 66%), attention received by professionals (92.5% vs. 86.1%), and information received on treatment (79.4% vs. 77.4%). In relation to confidentiality, results obtained were similar in both pharmacy settings. Conclusion: Dispensing OHM through the community pharmacy was a strategy associated with greater patient satisfaction as compared with OHM collection at the hospital pharmacy service, with greater accessibility, mainly due to close distance to the patient's home. The participation of community pharmacists could further optimize the care received by patients undergoing OHM treatment.

School bullying in children and adolescents with neurodevelopmental and psychiatric conditions: a systematic review and meta-analysis.

BACKGROUND: Bullying is a common form of violence among children and adolescents. Young people with neurodevelopmental or psychiatric conditions might have an increased risk of bullying victimisation and perpetration. We aimed to assess the odds of bullying involvement and its association with mental health measures in these populations. METHODS: In this systematic review and meta-analysis, we searched PubMed, ERIC, Psychology and Behavioural Sciences Collection, Web of Science Core Collection, PsycArticles, and PsycInfo databases from inception up to Aug 8, 2023, and included articles reporting data on bullying outcomes of current bullying (within the past year) among children and adolescents (aged 4-17 years) with a diagnosis of a neurodevelopmental or psychiatric condtion provided by a health professional. Bullying type was classified as traditional (physical, verbal, or relational) or as cyberbullying (intentional and repeated harm inflicted through electronic devices and social media), and bullying involvement was classified as victimisation, perpetration, and perpetration-victimisation. Mental health measures were collected and the associations with bullying involvement assessed. We used random-effects meta-analyses to estimate prevalence and odds ratios (ORs) for bullying involvement. Heterogeneity was assessed using the I2 statistic, and publication bias was tested with Egger's regression. This study is registered with PROSPERO, CRD42021235043. FINDINGS: We included 212 studies in the meta-analysis. The total sample comprised 126 717 cases (mean age 12·34 years [SD 1·82], 37·6% girls) and 504 806 controls (12·5 years [SD 1·86], 47·6% girls). For traditional bullying, the pooled prevalence was 42·2% (95% CI 39·6-44·9) for victimisation, 24·4% (22·6-26·3) for perpetration, and 14·0% (11·4-17·1) for perpetration-victimisation. For cyberbullying, the prevalence was 21·8% (16·0-28·9) for victimisation, 19·6% (13·4-27·7) for perpetration, and 20·7% (8·4-42·6) for perpetration-victimisation. Compared with controls, young people with neurodevelopmental or psychiatric conditions were more likely to be involved in traditional and cyberbullying as a victim (OR 2·85 [95% CI 2·62-3·09] and 2·07 [1·63-2·61]), perpetrator (2·42 [2·20-2·66] and 1·91 [1·60-2·28]), and perpetrator-victim (3·66 [2·83-4·74] and 1·85 [1·05-3·28]). Bullying involvement was associated with higher scores in mental health measures in young people with neurodevelopmental or psychiatric conditions, particularly internalising symptoms and externalising symptoms. INTERPRETATION: Our study underscores bullying involvement as a prevalent risk factor in young people with neurodevelopmental or psychiatric conditions that might add to their disease burden through its negative effects on mental health. Interventions targeting these vulnerable populations are warranted to improve their mental health and their future social integration. FUNDING: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Consorcio Centro de Investigación Biomédica en Red.

Impact of SCHOLAR-1 Criteria on Chimeric Antigen Receptor T Cell Therapy Efficacy in Aggressive B Lymphoma: A Real-World GELTAMO/GETH Study.

In the pre-chimeric antigen receptor T cell (CAR-T) therapy era, the SCHOLAR-1 study identified a group of patients with refractory aggressive B cell lymphoma (ABCL) with particularly poor prognoses. We recently published our real-world data from Spain, focused on this SCHOLAR-1 refractory group, and compared patients who underwent CAR-T therapy with the previous standard of care. In this study, we found that the efficacy of CAR-T therapy in refractory patients, in terms of progression-free survival (PFS) and overall survival (OS), was superior to that of the treatments available in the pre-CAR-T era. The main objective of these new analyses was to analyze treatment efficacy in terms of response rates and survival for patients with ABCL with or without the SCHOLAR-1 criteria. In addition, we analyzed the prognostic impact of each SCHOLAR-1 criterion independently. Our study aimed to assess the prognostic impact of SCHOLAR-1 criteria on ABCL patients treated with CAR-T therapy in Spain. This multicenter, retrospective, observational study. We included all adult patients treated with commercially available CAR-T cell products and diagnosed with ABCL different from primary mediastinal large B cell lymphoma between February 2019 and July 2022. Patients meeting any SCHOLAR-1 criteria (progressive disease as the best response to any line of therapy, stable disease as the best response to ≥4 cycles of first-line therapy or ≥2 cycles of later-line therapy, or relapse at <12 months after autologous stem cell transplantation [auto-SCT]) in the line of treatment before CAR-T therapy (SCHOLAR-1 group) were compared with those not meeting any of these criteria (non-SCHOLAR-1 group). To analyze the prognostic impact of individual SCHOLAR-1 criteria, all the patients who met any of the SCHOLAR-1 criteria at any time were included to assess whether these criteria have the same prognostic impact in the CAR-T era. In addition, patients were grouped according to whether they were refractory to the first line of treatment, refractory to the last line of treatment, or relapsed early after auto-SCT. The PFS and OS were calculated from the time of appearance of the SCHOLAR-1 refractoriness criteria. Of 329 patients treated with CAR-T (169 with axi-cel and 160 with tisa-cel), 52 were in the non-SCHOLAR-1 group and 277 were in the SCHOLAR-1 group. We found significantly better outcomes in the non-SCHOLAR-1 patients compared with the SCHOLAR-1 patients (median PFS of 12.2 and 3.3 months, respectively; P = .009). In addition, axi-cel showed better results in terms of efficacy than tisa-cel for both the non-SCHOLAR-1 group (hazard ratio [HR] for PFS, 2.7 [95% confidence interval (CI), 1.1 to 6.7; P = .028]; HR for OS, 7.1 [95% CI, 1.5 to 34.6; P = .015]) and SCHOLAR-1 group (HR for PFS, 1.8 [95% CI, 1.3 to 2.5; P < .001]; HR for OS, 1.8 [95% CI, 1.2 to 2.6; P = .002]), but also significantly more toxicity. Finally, separately analyzing the prognostic impact of each SCHOLAR-1 criterion revealed that refractoriness to the last line of treatment was the variable with the most significant impact on survival. In conclusion, SCHOLAR-1 refractoriness criteria notably influence the efficacy of CAR-T therapy. In our experience, axi-cel showed better efficacy than tisa-cel for both SCHOLAR-1 and non-SCHOLAR-1 patients. Refractoriness to the last line of treatment was the variable with the most significant impact on survival in the CAR-T therapy era.

Glycerol contributes to tuberculosis susceptibility in male mice with type 2 diabetes.

Diabetes mellitus increases risk for tuberculosis disease and adverse outcomes. Most people with both conditions have type 2 diabetes, but it is unknown if type 1 and type 2 diabetes have identical effects on tuberculosis susceptibility. Here we show that male mice receiving a high-fat diet and streptozotocin to model type 2 diabetes, have higher mortality, more lung pathology, and higher bacterial burden following Mycobacterium tuberculosis infection compared to mice treated with streptozotocin or high-fat diet alone. Type 2 diabetes model mice have elevated plasma glycerol, which is a preferred carbon source for M. tuberculosis. Infection studies with glycerol kinase mutant M. tuberculosis reveal that glycerol utilization contributes to the susceptibility of the type 2 diabetes mice. Hyperglycemia impairs protective immunity against M. tuberculosis in both forms of diabetes, but our data show that elevated glycerol contributes to an additional adverse effect uniquely relevant to type 2 diabetes.

Burnout syndrome and work engagement in nursing staff: a systematic review and meta-analysis.

Background: A difficult and demanding work environment, such as that often experienced in healthcare, can provoke fatigue, anxiety, distress, and discomfort. This study considers factors that may influence levels of burnout and work engagement among nurses and seeks to determine the relationship between these conditions. Method: A systematic scoping review was performed, in accordance with the PRISMA Extension for Scoping Reviews, based on data obtained from a search of the PubMed/MEDLINE and Scopus databases carried out in 2022 using the search equation: "work engagement AND nurs* AND burnout." This search identified nine quantitative primary studies suitable for inclusion in our analysis. Results: Work overload, type of shift worked, and/or area of hospital service, among other elements, are all relevant to the development of burnout. This syndrome can be countered by social support and appropriate personal resources and values, which are all positively associated with work engagement. Our analysis revealed a significant correlation between work engagement and the different domains of burnout. The correlation effect size between burnout and work engagement was -0.46 (95% CI -0.58, -0.31), with p < 0.001. Conclusion: Well-targeted interventions in the healthcare work environment can reduce burnout levels, strengthen work engagement, and enhance the quality of healthcare.

[Translated article] Advances in the work of multidisciplinary teams for the care of patients with severe uncontrolled asthma. A post-COVID vision (TEAM 2.0 project).

Asthma is a chronic respiratory disease with a high health, social and economic impact, particularly in the case of Severe Uncontrolled Asthma (SUA). For this reason, new strategies are especially necessary to improve its approach, with a personalized approach to each patient and from a multidisciplinary perspective, in addition to integrating the new telemedicine and telepharmacy practices promoted as a result of the COVID-19 pandemic. In this context, the TEAM 2.0 project ("Work in Multidisciplinary Asthma Teams") has been developed, following the TEAM project carried out in 2019, with the aim of updating and prioritizing good multidisciplinary work practices in SUA in a post pandemic context and analyze the progress made. A coordinating group, made up of eight multidisciplinary teams of hospital pharmacists, pulmonologists, and allergists, carried out an updated bibliographic review, sharing of good multidisciplinary practices, and analysis of advances. Through five regional meetings with other experts with experience in SUA, the good practices identified were shared and subjected to debate, evaluation and prioritization. In total, 23 good multidisciplinary work practices in SUA, grouped into five work areas: 1) Organization of work in multidisciplinary teams, 2) Patient education, self-management and adherence, 3) Health results, data monitoring and persistence, 4) Telepharmacy and experiences implemented during the COVID-19 pandemic and 5) Training and research, were evaluated and prioritized by 57 professionals from the field of Hospital Pharmacy, Pulmonology, Allergology and Nursing. This work has made it possible to update the roadmap of priority actions to continue advancing in optimal models of care for patients with AGNC in a post-COVID-19 context.

Advances in the work of multidisciplinary teams for the care of patients with severe uncontrolled asthma. A post-COVID vision (TEAM 2.0 project). / Avances en el trabajo de equipos multidisciplinares para la atención al paciente con asma grave no controlada. Una visión post-COVID (Proyecto TEAM 2.0).

Asthma is a chronic respiratory disease with a high health, social and economic impact, particularly in the case of Severe Uncontrolled Asthma (SUA). For this reason, new strategies are especially necessary to improve its approach, with a personalized approach to each patient and from a multidisciplinary perspective, in addition to integrating the new telemedicine and telepharmacy practices promoted as a result of the COVID-19 pandemic. In this context, the TEAM 2.0 project ("Work in Multidisciplinary Asthma Teams") has been developed, following the TEAM project carried out in 2019, with the aim of updating and prioritizing good multidisciplinary work practices in SUA in a post pandemic context and analyze the progress made. A coordinating group, made up of eight multidisciplinary teams of hospital pharmacists, pulmonologists, and allergists, carried out an updated bibliographic review, sharing of good multidisciplinary practices, and analysis of advances. Through five regional meetings with other experts with experience in SUA, the good practices identified were shared and subjected to debate, evaluation and prioritization. In total, 23 good multidisciplinary work practices in SUA, grouped into five work areas: 1) Organization of work in multidisciplinary teams, 2) Patient education, self-management and adherence, 3) Health results, data monitoring and persistence, 4) Telepharmacy and experiences implemented during the COVID-19 pandemic and 5) Training and research, were evaluated and prioritized by 57 professionals from the field of Hospital Pharmacy, Pulmonology, Allergology and Nursing. This work has made it possible to update the roadmap of priority actions to continue advancing in optimal models of care for patients with AGNC in a post-COVID-19 context.

Changing Trends in the Global Consumption of Treatments Used in Hospitalized Patients for COVID-19: A Time Series Multicentre Study.

AIM: To analyze trends in the prescription of COVID-19 treatments for hospitalized patients during the pandemic. METHODS: Multicenter, ecological, time-series study of aggregate data for all adult patients with COVID-19 treated in five acute-care hospitals in Barcelona, Spain, between March 2020 and May 2021. Trends in the monthly prevalence of drugs used against COVID-19 were analyzed by the Mantel-Haenszel test. RESULTS: The participating hospitals admitted 22,277 patients with COVID-19 during the study period, reporting an overall mortality of 10.8%. In the first months of the pandemic, lopinavir/ritonavir and hydroxychloroquine were the most frequently used antivirals, but these fell into disuse and were replaced by remdesivir in July 2020. By contrast, the trend in tocilizumab use varied, first peaking in April and May 2020, declining until January 2021, and showing a discrete upward trend thereafter. Regarding corticosteroid use, we observed a notable upward trend in the use of dexamethasone 6 mg per day from July 2020. Finally, there was a high prevalence of antibiotics use, especially azithromycin, in the first three months, but this decreased thereafter. CONCLUSIONS: Treatment for patients hospitalized with COVID-19 evolved with the changing scientific evidence during the pandemic. Initially, multiple drugs were empirically used that subsequently could not demonstrate clinical benefit. In future pandemics, stakeholders should strive to promote the early implementation of adaptive randomized clinical trials.

Genetic and Structural Brain Correlates of Cognitive Subtypes Across Youth at Family Risk for Schizophrenia and Bipolar Disorder.

OBJECTIVE: Cognitive impairment is an important feature of schizophrenia (SZ) and bipolar disorder (BP) with severity across the two disorders characterized by significant heterogeneity. Youth at family risk for SZ and BP were clustered based on cognitive function and examined in terms of the clinical, genetic, and brain imaging correlates of cluster membership. METHOD: One hundred sixty participants, 32 offspring of patients with SZ, 59 offspring of patients with BP and 69 offspring of healthy control parents underwent clinical and cognitive assessments, genotyping and structural MRI. K-means clustering was used to group family risk participants based on cognitive measures. Clusters were compared in terms of cortical and subcortical brain measures as well as polygenic risk scores. RESULTS: Participants were grouped in 3 clusters with intact, intermediate, and impaired cognitive performance. The intermediate and impaired clusters had lower total brain surface area compared with the intact cluster, with prominent localization in frontal and temporal cortices. No between-cluster differences were identified in cortical thickness and subcortical brain volumes. The impaired cluster also had poorer psychosocial functioning and worse PRS-COG compared with the other 2 clusters and with offspring of healthy control parents, while there was no significant between-cluster difference in terms of PRS-SZ and PRS-BP. PRS-COG predicted psychosocial functioning, yet this effect did not appear to be mediated by an effect of PRS-COG on brain area. CONCLUSION: Stratification based on cognition may help to elucidate the biological underpinnings of cognitive heterogeneity across SZ and BP risk.

Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide.

Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-transplant cyclophosphamide (PTCy) and the effects of Tac IPV on the occurrence of acute GVHD (aGVHD) were analyzed. Tac IPV was calculated from pre-dose concentrations (C0) measured during the first month after Tac initiation. The cumulative rates of grades II-IV and grades III-IV aGVHD at day +100 were 22.7% and 7%, respectively. Higher Tac IPV was associated with a greater risk of developing GVHD, with patients having IPV > 50th percentile having significantly higher rates of grades II-IV (34.9% vs. 10.8%; hazard ratio [HR] 3.858, p < 0.001) and grades III-IV (12.7% vs. 1.5%; HR 9.69, p = 0.033) aGVHD than patients having IPV ≤ 50th percentile. Similarly, patients with IPV > 75th percentile had higher rates of grades II-IV (41.9% vs. 16.5%; HR 3.30, p < 0.001) and grades III-IV (16.1% vs. 4.1%; HR 4.99, p = 0.012) aGVHD than patients with IPV ≤ 75th percentile. Multivariate analyses showed that high Tac IPV (>50th percentile) was an independent risk factor for grades II-IV (HR 2.99, p = 0.018) and grades III-IV (HR 9.12, p = 0.047) aGVHD. Determination of Tac IPV soon after alloHSCT could be useful in identifying patients at greater risk of aGVHD.

Global trends of dalbavancin: A bibliometric analysis.

WHAT IS KNOWN AND OBJECTIVE?: Dalbavancin is used against gram-positive pathogens such as Staphylococcus aureus in acute bacterial skin and skin-structure infections. METHODS: Our main goal was to identify the key articles sustaining the current knowledge of this drug's therapeutic possibilities through a bibliometric analysis of the available literature. RESULTS AND DISCUSSION: On 15 March 2021, we searched the Web of Science electronically for documents that contain within its title the term "dalbavancin." We found a total of 675 documents that average 20.23 citations/publication with a density of 682.60 citations per/year, yielding an h-index of 58. After ranking them by the number of times cited, we extracted the top 100 most-cited records (T100). Number of citations/publication ranged from 13 to 231, publication years were 2002-2019, with the top-cited article published in 2014. All T100 publications were written in English. JMI Laboratories was the institution with the most articles in the T100 (22 documents), and the United States was the top country (75 documents). Five authors participated in at least five of the T100, led by Jones RN with 20 articles. Positions #1, #2, #5, and #9 were clinical trials for acute bacterial skin and skin structure infections (ABSSSI), the on-label indication for dalbavancin. Only one article in the top 10 (T10) was an off-label indication that was published in 2005 with 186 citations, and occupied the third position among the T100. Using the VOSviewer© programme, we observed that the most used keywords were: dalbavancin, lipoglycopeptide, gram-positive, osteomyelitis, vancomycin, and MRSA. WHAT IS NEW AND CONCLUSIONS?: Our study identifies the most significant research on dalbavancin, including the highest impact publications, and highlights the recent trend of dalbavancin in new therapies. The T10 articles include the most important dalbavancin clinical trials, along with other studies and reviews that support the growing role of this antibiotic in clinical use. Emphasis has been on the favourable pharmacokinetic profile that allows administration once-weekly, with minimal risk of severe adverse events.

Economic impact of obstetric events on women of reproductive age living with psoriatic arthritis, rheumatoid arthritis, axial spondyloarthritis and psoriasis in Spain.

OBJECTIVE: To estimate the annual cost associated with obstetric events in women of reproductive age with immune-mediated inflammatory diseases, from the perspective of the National Healthcare System. METHODS: A cost-analysis was developed to estimate the impact associated with obstetric events in women of reproductive age with psoriasis (PSO), psoriatic arthritis (PsA), rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA). The analysis considered complications during fertility and conception, in pregnancy and in the postpartum. All parameters were validated and agreed by a multidisciplinary expert panel. Unitary costs (€,2019) were obtained from national, local databases. RESULTS: During fertility and conception, an annual cost per patient of €229 was estimated for a preconception consultation in a patient with PSO, of €3642 for a preconception consultation in patients with PsA, RA and axSpA and €4339 for assisted reproduction. Women with complications in pregnancy had an annual cost per patient of €1214 for a miscarriage in the first trimester, €4419 for a late miscarriage in the second trimester, €11,260 for preeclampsia €3188 for restricted intrauterine growth and €12,131 for threat of premature delivery. In the postpartum, an annual cost per patient of €120,364, €44,709, and €5507 were estimated associated with admissions to neonatology of premature infants of <28, 28-32 and 33-37 weeks, respectively. CONCLUSIONS: This analysis provides insight on the economic burden of complications associated with women of reproductive age for immune-mediated diseases (PSO, PsA, RA, axSpA). Individualization of treatment, additional and close monitoring may reduce the risk and burden of these complications.

[Cutaneous Rosai-Dorfman disease with lack of BRAF-V600, KRAS or NRAS mutations: A reactive or neoplastic disorder?] / Enfermedad de Rosai-Dorfman con presentación cutánea y ausencia de mutaciones BRAF-V600, KRAS y NRAS: ¿trastorno neoplásico o reactivo.

Non-Langerhans cell histiocytosis, including Rosai-Dorfman disease (RDD) and xanthogranuloma are rare disorders with occasional overlapping in the histopathological and immunohistochemical (IHC) findings. We report the case of a 53-year-old woman with erythematous-violaceous plaques on the cheeks and edema in the auricular pavilions. A biopsy was performed and the histopathological examination revealed a histiocytic proliferation with emperipolesis characteristic of RDD and lymphoplasmocitic infiltrate. IHC analysis showed S100 and CD68 positivity in the histiocytes but was negative for CD1a, supporting the diagnosis of RDD. Molecular analysis failed to detect BRAF-V600, NRAS or KRAS mutation. We discuss the differential diagnosis of cutaneous non-Langerhans cell histiocytosis. Pathologist must be aware of unusual presentations of RDD and further treatment options must be explored for patients with unresectable lesions and/or resistance to the classical management of RDD.

Acute Bacterial Skin and Skin-Structure Infections, efficacy of Dalbavancin: a systematic review and meta-analysis.

OBJECTIVES: To know the efficacy of different doses of dalbavancin in acute bacterial skin and skin-structure infections (ABSSSIs) and versus other antibiotics. METHODS: We performed a systematic review of dalbavancin efficacy for ABSSSIs. We selected 10 clinical trials from MEDLINE and Cochrane databases for qualitative review. Of these, five trials compared one or two doses of dalbavancin versus other antibiotics such as vancomycin or linezolid. RESULTS: Treatment outcomes with other antibiotics were not significantly different versus two doses of dalbavancin (OR 1.13; 95% CI 0.75-1.71; p = 0.55) or single dose dalbavancin (OR 0.98; 95% CI 0.19-5.17; p = 0.98). One dose versus two doses of dalbavancin did not show significant differences in any of the treatment groups. In contrast, the global microbiological assessment results indicated a favorable outcome for two doses of dalbavancin compared to the single dose of dalbavancin (OR 2.96; 95% CI 1.19-7.39; p = 0.02) in both methicillin-resistant and methicillin-susceptible Staphylococcus aureus. CONCLUSION: Either single dose or two dose dalbavancin treatment is as clinically effective as other antibiotics such as vancomycin and linezolid for the treatment of ABSSSIs.Abbreviations ABSSI: acute bacterial skin and skin-structure infection; AUC: area under the concentration-time curve; CE: clinical evaluable; CI: confidence interval; EOT: end of treatment; ITT: intention-to-treat; LOS: length of stay; MIC: minimum inhibitory concentration; MIC90: minimum concentration to inhibit growth of 90% of isolates; MR: methicillin resistant; MRSA: methicillin-resistant Staphylococcus aureus; MS: methicillin susceptible; MSSA: methicillin-susceptible Staphylococcus aureus; OPAT: Outpatient Parenteral Antimicrobial Therapy; OR: odds ratio; PI: penicillin intermediate; PR: penicillin resistant; PS penicillin susceptible; SIRS: systemic inflammatory response syndrome; SSTI: skin and soft tissue infection; TOC: test of cure; VR: vancomycin resistant; VS: vancomycin susceptible.

Surgery and Radiosurgery in Autism: A Retrospective Study in 10 Patients.

INTRODUCTION: A subgroup of patients with autism spectrum disorder (ASD) show self or heteroaggression, dyscontrol episodes, and others are of obsessive-compulsive disorder (OCD) profile; some of them are resistant to medical and behavioural treatment. We describe the long-term outcome in a group of these patients, treated with radiofrequency brain lesions or combined stereotactic surgery and Gamma Knife (GK) radiosurgery. METHODS: We reviewed the medical records of 10 ASD patients with pathological aggressiveness and OCD, who had undergone radiofrequency lesions and/or radiosurgery with GK in our institution. RESULTS: The 10 patients had a significant reduction of their symptoms (PCQ 39.9 and 33, OAS 11.8 and 5, CYBOCS-ASD 30.4 and 20), preoperatively and in the last follow-up, respectively; p < 0.005 (in all cases), although all but 2 needed more than 1 treatment to maintain this improvement. CONCLUSIONS: We observed a marked improvement in behaviour, quality of life, and relationship with the environment in all our 10 patients after the lesioning treatments, without long-lasting side effects.

Younger Age in Adolescent Pregnancies Is Associated with Higher Risk of Adverse Outcomes.

Adolescent pregnancy remains a health issue worldwide also in developed countries, since it has been associated with adverse maternal and neonatal outcomes. Some data suggest that very young adolescents have higher risk, likely due to immaturity. Therefore, we aimed to assess the influence of maternal age on complications during gestation and labor in pregnant women between 13 and 19 years of age. In particular, we evaluated the possible association between maternal age and obstetric, fetal and labor complications. This is a retrospective, observational and exploratory study conducted at Hospital Universitario La Paz (HULP, Madrid, Spain). The clinical history of 279 women who delivered between 2013 and 2018 was analyzed. Maternal age and the presence of maternal, fetal and labor complications, as well as risk of postpartum depression and breastfeeding intention, were recorded. General regression models were used to analyze the contribution of maternal age on each complication. The percentage of adolescent pregnancies at HULP between 2013 and 2018 was 0.9%. The risk of all the maternal complications analyzed decreased significantly with every year of age of the mother (hyperemesis, lower back pain, anemia, gestational diabetes mellitus, and threat of premature labor and premature rupture of membranes). Every year of maternal age decreased 0.8-fold [0.8; 0.9] the prevalence of fetal complications and also reduced the risk of C-section, postpartum hemorrhage and obstetrical hysterectomy. Furthermore, higher maternal age increased 1.1-fold [1.0; 1.2] the breastfeeding intention. In conclusion, young adolescents are at higher risk of complications during pregnancy and labor.

Sirtuin 3 Downregulation in Mycobacterium tuberculosis-Infected Macrophages Reprograms Mitochondrial Metabolism and Promotes Cell Death.

Mycobacterium tuberculosis induces metabolic reprogramming in macrophages like the Warburg effect. This enhances antimicrobial performance at the expense of increased inflammation, which may promote a pathogen-permissive host environment. Since the NAD+-dependent protein deacetylase Sirtuin 3 (SIRT3) is an important regulator of mitochondrial metabolism and cellular redox homeostasis, we hypothesized that SIRT3 modulation mediates M. tuberculosis-induced metabolic reprogramming. Infection of immortalized and primary murine macrophages resulted in reduced levels of SIRT3 mRNA and protein and perturbation of SIRT3-regulated enzymes in the tricarboxylic acid cycle, electron transport chain, and glycolytic pathway. These changes were associated with increased reactive oxygen species and reduced antioxidant scavenging, thereby triggering mitochondrial stress and macrophage cell death. Relevance to tuberculosis disease in vivo was indicated by greater bacterial burden and immune pathology in M. tuberculosis-infected Sirt3-/- mice. CD11b+ lung leukocytes isolated from infected Sirt3-/- mice showed decreased levels of enzymes involved in central mitochondrial metabolic pathways, along with increased reactive oxygen species. Bacterial burden was also greater in lungs of LysMcreSirt3L2/L2 mice, demonstrating the importance of macrophage-specific SIRT3 after infection. These results support the model of SIRT3 as a major upstream regulatory factor, leading to metabolic reprogramming in macrophages by M. tuberculosisIMPORTANCE Tuberculosis, the disease caused by the bacterium M. tuberculosis, remains one of the top 10 causes of death worldwide. Macrophages, the first cells to encounter M. tuberculosis and critical for defense against infection, are hijacked by M. tuberculosis as a protected growth niche. M. tuberculosis-infected macrophages undergo metabolic reprogramming where key mitochondrial pathways are modulated, but the mechanisms driving this metabolic shift is unknown. Our study demonstrates that M. tuberculosis downregulates Sirtuin 3 (SIRT3), an important regulator of mitochondrial metabolism, leading to SIRT3-dependent transcriptional downregulation of mitochondrial metabolic proteins, which is followed by oxidative stress and macrophage necrosis. This study identifies SIRT3 modulation as a key event in M. tuberculosis-induced metabolic reprograming in macrophages that defend against tuberculosis.

Economic Impact of Obstetric Events on Women of Reproductive Age Living With Psoriatic Arthritis, Rheumatoid Arthritis, Axial Spondyloarthritis and Psoriasis in Spain. / Impacto económico asociado a eventos obstétricos en mujeres en edad fértil con artritis psoriásica, artritis reumatoide, espondiloartritis axial y psoriasis en España.

OBJECTIVE: To estimate the annual cost associated with obstetric events in women of reproductive age with immune-mediated inflammatory diseases, from the perspective of the National Healthcare System. METHODS: A cost-analysis was developed to estimate the impact associated with obstetric events in women of reproductive age with psoriasis (PSO), psoriatic arthritis (PsA), rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA). The analysis considered complications during fertility and conception, in pregnancy and in the postpartum. All parameters were validated and agreed by a multidisciplinary expert panel. Unitary costs (€, 2019) were obtained from national, local databases. RESULTS: During fertility and conception, an annual cost per patient of €229 was estimated for a preconception consultation in a patient with PSO, of €3,642 for a preconception consultation in patients with PsA, RA and axSpA and €4,339 for assisted reproduction. Women with complications in pregnancy had an annual cost per patient of €1,214 for a miscarriage in the first trimester, €4,419 for a late miscarriage in the second trimester, €11,260 for preeclampsia €3,188 for restricted intrauterine growth and €12,131 for threat of premature delivery. In the postpartum, an annual cost per patient of €120,364, €44,709, and €5,507 were estimated associated with admissions to neonatology of premature infants of <28, 28-32 and 33-37 weeks, respectively. CONCLUSIONS: This analysis provides insight on the economic burden of complications associated with women of reproductive age for immune-mediated diseases (PSO, PsA, RA, axSpA). Individualization of treatment, additional and close monitoring may reduce the risk and burden of these complications.

Metformin enhances anti-mycobacterial responses by educating CD8+ T-cell immunometabolic circuits.

Patients with type 2 diabetes (T2D) have a lower risk of Mycobacterium tuberculosis infection, progression from infection to tuberculosis (TB) disease, TB morality and TB recurrence, when being treated with metformin. However, a detailed mechanistic understanding of these protective effects is lacking. Here, we use mass cytometry to show that metformin treatment expands a population of memory-like antigen-inexperienced CD8+CXCR3+ T cells in naive mice, and in healthy individuals and patients with T2D. Metformin-educated CD8+ T cells have increased (i) mitochondrial mass, oxidative phosphorylation, and fatty acid oxidation; (ii) survival capacity; and (iii) anti-mycobacterial properties. CD8+ T cells from Cxcr3-/- mice do not exhibit this metformin-mediated metabolic programming. In BCG-vaccinated mice and guinea pigs, metformin enhances immunogenicity and protective efficacy against M. tuberculosis challenge. Collectively, these results demonstrate an important function of CD8+ T cells in metformin-derived host metabolic-fitness towards M. tuberculosis infection.