From basic research to clinical practice: The impact of laminar airflow filters on surgical site infection in vascular surgery.

BACKGROUND: Laminar airflow filters have been suggested as a potential preventive factor for surgical site infections, given their ability to reduce the airborne microbiological load. However, their role is still unclear, and evidence regarding vascular surgery patients is scarce. Our aim was to assess the impact of laminar-airflow filters on surgical site infections. METHODS: This single-centre retrospective cohort study was conducted with vascular surgery patients who underwent arterial vascular intervention through a groin incision between July 2018 and July 2019 (turbulent airflow cohort) and July 2020 and July 2021 (laminar airflow cohort). Data were prospectively collected from electronic medical files. We estimated the cumulative incidence of surgical site infections and its 95% confident interval (95%CI). A propensity score matching analysis was performed. RESULTS: We included 200 patients, 78 in the turbulent airflow cohort and 122 in the laminar airflow cohort. The cumulative incidence was 15.4% (12/78; 95%CI: 9.0-25.0%) in the turbulent-airflow cohort and 14.8% (18/122; 95%CI: 9.5 -22.1%) in the laminar-airflow cohort (p-value: 1.00). The propensity score matching yielded a cumulative incidence of surgical site infection of 13.9% (10/72) with turbulent airflow and 12.5% (9/72) with laminar airflow (p-value: 1.00). Risk factors associated with infection were chronic kidney disease (OR 2.70; 95%CI: 1.14-6.21) and a greater body mass index (OR 1.47; 95%CI: 1.01-2.14). CONCLUSION: Laminar airflow filters were associated with a non-significant reduction of surgical site infections. Further research is needed to determine its usefulness and cost-effectiveness. Surgical site infection incidence was associated with chronic kidney disease and a greater body mass index. Hence, efforts should be made to optimize the body mass index before surgery and prevent chronic kidney disease in patients with known arterial disease.

Pain in Long-Term Cancer Survivors: Prevalence and Impact in a Cohort Composed Mostly of Breast Cancer Survivors.

Cancer survival is becoming more common which means that there is now a growing population of cancer survivors, in whom pain may be common. However, its prevalence has hardly been addressed systematically. We aimed to assess the prevalence and explore the pathophysiology and impact of pain on health outcomes in cancer survivors. We conducted a retrospective-prospective cohort study in cancer-free patients diagnosed with cancer at least five years before the study start date. We used multivariable regression to establish the association of patients' cancer characteristics with pain, and then the association of patients' pain features with health outcomes and related symptoms. Between March and July 2021, 278 long-term cancer survivors were evaluated. Almost half of them (130/278, 46.8%) had pain, of whom 58.9% had a probable neuropathic component, but only 18 (13.8%) were taking specific drugs for neuropathic pain. A history of surgery-related pain syndrome in breast cancer patients was more than twice as frequent in the pain cohort. Post-chemotherapy and post-radiotherapy pain syndromes were uncommon. Pain was associated with lower QoL, emotional functioning, professional performance, and disability scores. Pain is a frequent health determinant in cancer survivors. Referral to specialised pain services may be a reasonable move in some cases.

Effect and safety of listening to music or audiobooks as a coadjuvant treatment for chronic pain patients under opioid treatment: a study protocol for an open-label, parallel-group, randomised, controlled, proof-of-concept clinical trial in a tertiary hospital in the Barcelona South Metropolitan area.

BACKGROUND: Chronic non-cancer pain (CNCP) treatment's primary goal is to maintain physical and mental functioning while improving quality of life. Opioid use in CNCP patients has increased in recent years, and non-pharmacological interventions such as music listening have been proposed to counter it. Unlike other auditive stimuli, music can activate emotional-regulating and reward-regulating circuits, making it a potential tool to modulate attentional processes and regulate mood. This study's primary objective is to provide the first evidence on the distinct (separate) effects of music listening as a coadjuvant maintenance analgesic treatment in CNCP patients undergoing opioid analgesia. METHODS AND ANALYSIS: This will be a single-centre, phase II, open-label, parallel-group, proof-of-concept randomised clinical trial with CNCP patients under a minimum 4-week regular opioid treatment. We plan to include 70 consecutive patients, which will be randomised (1:1) to either the experimental group (active music listening) or the control group (active audiobooks listening). During 28 days, both groups will listen daily (for at least 30 min and up to 1 hour) to preset playlists tailored to individual preferences.Pain intensity scores at each visit, the changes (differences) from baseline and the proportions of responders according to various definitions based on pain intensity differences will be described and compared between study arms. We will apply longitudinal data assessment methods (mixed generalised linear models) taking the patient as a cluster to assess and compare the endpoints' evolution. We will also use the mediation analysis framework to adjust for the effects of additional therapeutic measures and obtain estimates of effect with a causal interpretation. ETHICS AND DISSEMINATION: The study protocol has been reviewed, and ethics approval has been obtained from the Bellvitge University Hospital Institutional Review Board, L'Hospitalet de Llobregat, Barcelona, Spain. The results from this study will be actively disseminated through manuscript publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05726266.

Bacterial immunotherapy is highly effective in reducing recurrent upper respiratory tract infections in children: a prospective observational study.

PURPOSE: Whilst immunotherapy is an appealing option as it could reduce the burden of recurrent pediatric respiratory tract infections (RTI), there is limited evidence on its effectiveness and more research was requested in order to better understand this therapeutic modality. METHODS: We performed a prospective cohort study involving 57 subjects to assess the safety and effectiveness a 3-month regimen of either typified or patient-specific bacterial lysates could have in reducing the number of RTIs in children aged 0 to 11 years with histories of recurrent episodes. RESULTS: After a 6-month follow-up, the number of RTIs and school absenteeism dropped sharply and significantly, from an adjusted mean (standard error) of 0.6 (0.04) episodes/month to 0.1 (0.03) episodes/month (74.7% reduction, P < 0.001), and from an adjusted mean score of 4.6 (1.06) points to 0.0 (0.01) points over 10 (99.5% reduction, P < 0.001), respectively. There was also a significant decrease in the severity of symptoms. No adverse reactions were observed. CONCLUSION: The use of the study product is associated with a decreased risk of recurrent RTIs in children, with a very favorable safety profile that warrants further investigation in randomized clinical trials.

Advances and Pitfalls of Specialized Pain Care through Public and Private Health Care Providers in Catalonia and the Balearic Islands: A Physician's Survey.

Optimal diagnosis and treatment of pain require a multidisciplinary approach that demands considerable coordination and forethought. A cross-sectional physician survey based on an online questionnaire was carried out to assess the adoption of multidisciplinary working patterns, compare the public and private models, and provide an update on the resources and organization of specialized pain care in Catalonia and the Balearic Islands. Active pain practitioners identified through the Catalan Health Service and Pain Society databases were sent an invitation in December 2020. Of the 321 physicians contacted, 91 (28.3%) answered and 71 provided complete responses (commonly anesthesiologists, representing 92 different sites; some worked at public and private sites). Up to 78.7% reported working in pain management teams, but only 53.5% were regularly involved in teaching or research activities. Thus, the proportion of multidisciplinary sites lies somewhere in-between. Median wait times were significantly shorter and within the recommended standards in private practices (e.g., 15 vs. 90 days in public practices for noncancer patients). In turn, private practices were slightly less staffed and equipped, albeit the differences did not reach statistical significance. Respondents made a median of 530 regular and 30 emergency visits per year, of which 190 involved interventional procedures. They offered a wide range of pharmacological and interventional therapies, although psychotherapy and the most sophisticated procedures were only available in ≤50% of sites. Pain clinicians and facilities are reasonably available in Catalonia, but barely more than half are truly multidisciplinary. Public and private practices differ in some aspects; the latter seems to be more accessible, but it is restricted to patients who can afford it. Compared to previous reports, this update shows both advances and outstanding issues. Multidisciplinary care could be expanded by incorporating more psychologists and some interventional procedures. The public practices should reduce wait times.

Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., ß-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.

A Patient-Based National Survey and Prospective Evaluation of Postoperative Pain Management in Spain: Prevalent but Possibly Preventable.

OBJECTIVE: To evaluate the national general prevalence of postoperative pain and the associated organizational/structural factors related to the provision of health care services. DESIGN AND SETTING: Observational prospective cohort study performed in 46 tertiary hospitals that were randomly selected from the Spanish National Inventory of Hospitals through a two-stage balanced and stratified procedure. SUBJECTS AND METHODS: Nine-hundred surgical patients representing a wide spectrum of surgical procedures and anesthetic methods were recruited. Those suffering moderate or worse pain while in the postanesthesia care unit/surgery ward (PACU/SW) were followed for 72 hours. Site characteristics were also surveyed. Multilevel models were used to evaluate center- and patient-level factors associated with pain and quality of recovery (QoR). Weighted generalized estimating equations were used to analyze the evolution of pain intensity. RESULTS: The prevalence while in and at discharge from the PACU/SW was 48.7% (cluster-adjusted 95% confidence interval [CI] = 38.1-59.2%) and 21.6% (95% CI = 15.4-27.8%), respectively. Pain intensity decreased significantly over time. Less than 20% of the patients received systemic patient-controlled analgesia (PCA) or regional analgesic techniques. Age, preexisting pain, type of surgery, use of general anesthesia, and postoperative potent opioids were associated with pain risk and intensity, as were center-level factors such as patient information, protocol availability, and coordination of care. In turn, QoR was related to pain intensity and patient satisfaction with analgesia and side effects. CONCLUSIONS: Compared with previous reports, the prevalence of moderate/severe postoperative pain has decreased but remains excessive. Organizational improvements to deploy procedure-specific, opioid-sparing analgesic strategies including regional techniques are recommended.

Improving the prediction of acute myeloid leukaemia outcomes by complementing mutational profiling with ex vivo chemosensitivity.

Refractoriness to induction therapy and relapse after complete remission are the leading causes of death in patients with acute myeloid leukaemia (AML). This study focussed on the prediction of response to standard induction therapy and outcome of patients with AML using a combined strategy of mutational profiling by next-generation sequencing (NGS, n = 190) and ex vivo PharmaFlow testing (n = 74) for the 10 most widely used drugs for AML induction therapy, in a cohort of adult patients uniformly treated according to Spanish PETHEMA guidelines. We identified an adverse mutational profile (EZH2, KMT2A, U2AF1 and/or TP53 mutations) that carries a greater risk of death [hazard ratio (HR): 3·29, P < 0·0001]. A high correlation was found between the ex vivo PharmaFlow results and clinical induction response (69%). Clinical correlation analysis showed that the pattern of multiresistance revealed by ex vivo PharmaFlow identified patients with a high risk of death (HR: 2·58). Patients with mutation status also ran a high risk (HR 4·19), and the risk was increased further in patients with both adverse profiles (HR 4·82). We have developed a new score based on NGS and ex vivo drug testing for AML patients that improves upon current prognostic risk stratification and allows clinicians to tailor treatments to minimise drug resistance.

Cholesterol-Lowering Treatment in Chronic Kidney Disease: Multistage Pairwise and Network Meta-Analyses.

Pairwise and network meta-analyses on the relationship between the efficacy of the use of statins with or without ezetimibe and reductions in low-density lipoprotein cholesterol (LDLc) and C-reactive protein (CRP) in patients with chronic kidney disease (CKD) are presented. In the pairwise meta-analysis, statins with or without ezetimibe were shown to be efficacious in reducing major adverse cardiovascular events (MACE) in patients with CKD and an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2, in the context of both primary prevention [odds ratio (OR)/95% confidence interval (95% CI)/I2/number of studies (n): 0.50/0.40-0.64/0%/6] and primary/secondary prevention (0.66/0.57-0.76/57%/18). However, in the Bayesian network meta-analysis, compared to the placebo, only atorvastatin 80 mg daily and atorvastatin and rosuvastatin at doses equivalent to simvastatin 20 mg daily reduced the odds of MACEs in this patient population. The network meta-analysis for LDLc and CRP treatment objectives also showed that, regardless of eGFR and excluding dialysis patients, the number of MACEs decreased in patients with CKD, with reductions in both LDLc and CRP of less than 50% (surface under the cumulative ranking (SUCRA)/heterogeneity (vague)/n: 0.77/0.14/3). The evaluation of the benefits of drugs may lead to individualized therapy for CKD patients: Cholesterol-lowering treatment for CKD patients with high levels of both LDLc and CRP is suggested.

Prescripción potencialmente inapropiada en pacientes en diálisis utilizando los criterios STOPP-START / Potentially inapropriate prescribing in patients on dialysis using STOPP-START criteria

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A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients.

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules.

A cross-sectional, comparative, syndromic description of oncological mixed pain in Medical Oncology units in Spain.

OBJECTIVE: The reason cancer pain remains prevalent and hard to classify may be partially explained by the failure to identify neuropathic mechanisms. The objective of this research was to identify the syndromes of cancer pain that may be particularly hard to manage due to their mixed pathophysiology. DESIGN: A series of 384 patients who had cancer of any type, at any stage, and suffered from chronic pain (symptom onset > 3 months) were assessed during a routine return visit in Spain. Medical oncologists indicated the presence and pathophysiology of 33 predefined pain syndromes on a per-patient basis. This information was then measured against clinical, psychosocial, and health care-related data to determine which syndromes pose particular challenges. RESULTS: The mean (standard deviation) age of patients was 61.6 (12.6) years, 49.7% were women. Most (82%) had advanced metastatic disease, 68.7% were on second-line or palliative therapies. The worst syndrome was nociceptive, pure neuropathic, and mixed in 34.6, 26.9, and 38.6% of patients, respectively. Any syndrome could be of mixed pathophysiology. Only 10 syndromes were common (≥ 5% of patients). Syndromes related to malignant bone pain and involvement of chest wall structures were the most frequent. Certain syndromes (including tumor-related bone pain, chemotherapy-induced peripheral neuropathies, paraneoplastic pain syndromes, and malignant neuralgias or injury to cranial nerves) can be particularly challenging when they have a mixed pathophysiology, because the neuropathic component is rarely or unevenly considered. CONCLUSIONS: Virtually all cancer pain syndromes can present mixed pathophysiology. Certain syndromes can include neuropathic components that are frequently overlooked.

Diagnostic accuracy of an identification tool for localized neuropathic pain based on the IASP criteria.

OBJECTIVE: Based on the clear neuroanatomical delineation of many neuropathic pain (NP) symptoms, a simple tool for performing a short structured clinical encounter based on the IASP diagnostic criteria was developed to identify NP. This study evaluated its accuracy and usefulness. METHODS: A case-control study was performed in 19 pain clinics within Spain. A pain clinician used the experimental screening tool (the index test, IT) to assign the descriptions of non-neuropathic (nNP), non-localized neuropathic (nLNP), and localized neuropathic (LNP) to the patients' pain conditions. The reference standard was a formal clinical diagnosis provided by another pain clinician. The accuracy of the IT was compared with that of the Douleur Neuropathique en 4 questions (DN4) and the Leeds Assessment of Neuropathic Signs and Symptoms (LANSS). RESULTS: Six-hundred and sixty-six patients were analyzed. There was a good agreement between the IT and the reference standard (kappa =0.722). The IT was accurate in distinguishing between LNP and nLNP (83.2% sensitivity, 88.2% specificity), between LNP and the other pain categories (nLNP + nNP) (80.0% sensitivity, 90.7% specificity), and between NP and nNP (95.5% sensitivity, 89.1% specificity). The accuracy in distinguishing between NP and nNP was comparable with that of the DN4 and the LANSS. The IT took a median of 10 min to complete. CONCLUSIONS: A novel instrument based on an operationalization of the IASP criteria can not only discern between LNP and nLNP, but also provide a high level of diagnostic certainty about the presence of NP after a short clinical encounter.

Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial.

This trial assessed the efficacy of MR309 (a novel selective sigma-1 receptor ligand previously developed as E-52862) in ameliorating oxaliplatin-induced peripheral neuropathy (oxaipn). A discontinuous regimen of MR309 (400 mg/day, 5 days per cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, placebo-controlled, multicenter clinical trial. Outcome measures included changes in 24-week quantitative measures of thermal sensitivity and total neuropathy score. In total, 124 patients were randomized (1:1) to MR309 or placebo. Sixty-three (50.8%) patients withdrew prematurely before completing 12 planned oxaliplatin cycles. Premature withdrawal because of cancer progression was less frequent in the MR309 group (7.4% vs 25.0% with placebo; p = 0.054). MR309 significantly reduced cold pain threshold temperature [mean treatment effect difference (SE) vs placebo: 5.29 (1.60)°C; p = 0.001] and suprathreshold cold stimulus-evoked pain intensity [mean treatment effect difference: 1.24 (0.57) points; p = 0.032]. Total neuropathy score, health-related quality-of-life measures, and nerve-conduction parameters changed similarly in both arms, whereas the proportion of patients with severe chronic neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Events ≥ 3) was significantly lower in the MR309 group (3.0% vs 18.2% with placebo; p = 0.046). The total amount of oxaliplatin delivered was greater in the active arm (1618.9 mg vs 1453.8 mg with placebo; p = 0.049). Overall, 19.0% of patients experienced at least 1 treatment-related adverse event (25.8% and 11.9% with MR309 and placebo, respectively). Intermittent treatment with MR309 was associated with reduced acute oxaipn and higher oxaliplatin exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile.

Recuentos de células T reguladoras en sangre periférica como biomarcador predictivo del resultado del trasplante renal: revisión sistemática / Peripheral blood regulatory T cell counts as a predictive biomarker for the outcome of kidney transplant: A systematic review

Fundamento y objetivo: Las células T reguladoras circulantes podrían convertirse en un adecuado biomarcador para los trasplantados renales. El objetivo de este estudio es evaluar el efecto de los inhibidores de la mammalian target of rapamycin (I-mTOR, «diana de rapamicina en células de mamífero») en las células reguladoras, y el interés clínico de este efecto. Material y métodos: Revisión sistemática de trabajos publicados y no publicados. Bases de datos y repositorios del mundo entero. Se buscaron ensayos controlados aleatorizados y estudios de cohortes que compararon recuentos de células reguladoras y episodios de rechazo entre trasplantados tratados con y sin I-mTOR. Los trabajos podían medir la correlación células reguladoras-filtrado glomerular. Se evaluó la codependencia células reguladoras-eficacia de los I-mTOR. Resultados: Se incluyeron 5 ensayos y 9 estudios. Las diferencias clínicas no permitieron una estimación cuantitativa del efecto de la inmunosupresión en el número de células reguladoras. Sin embargo, observamos que hay más células reguladoras con sirolimus o everolimus. El número de episodios de rechazo fue similar con anticalcineurínicos que con I-mTOR, a pesar de las diferencias en el número de células reguladoras. La correlación combinada células reguladoras-filtrado glomerular fue prospectivamente de 0,114, con un intervalo de confianza al 95% (IC 95%) de 0,062-0,406, y retrospectivamente, de 0,13 (IC 95% 0,0-0,361). Existen pruebas directas, aunque de bajo nivel (aleatorización estratificada por el biomarcador), respecto a la codependencia células reguladoras-eficacia de los I-mTOR. Conclusión: El número de células reguladoras puede asociarse a buenos resultados o desenlaces en los tratados con I-mTOR (eficacia antirrechazo), considerando la relación entre estas células y la función del injerto. Registro: PROSPERO (CRD42016046285) (AU)

Background and objective: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. Material and methods: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated. Results: Five trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy. Conclusions: Regulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function Registration: PROSPERO (CRD42016046285) (AU)

Peripheral blood regulatory T cell counts as a predictive biomarker for the outcome of kidney transplant: A systematic review. / Recuentos de células T reguladoras en sangre periférica como biomarcador predictivo del resultado del trasplante renal: revisión sistemática.

BACKGROUND AND OBJECTIVE: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. MATERIAL AND METHODS: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated. RESULTS: Five trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy. CONCLUSIONS: Regulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function. REGISTRATION: PROSPERO (CRD42016046285).

Mixed Pain Can Be Discerned in the Primary Care and Orthopedics Settings in Spain: A Large Cross-Sectional Study.

OBJECTIVES: To assess the value of the concept of mixed pain by investigating its acceptance and interpretation by health care professionals and the differential characteristics in patients with mixed pain. MATERIALS AND METHODS: Data from 5024 patients with pain from 551 sites in Primary Care and Orthopedics settings were analyzed in this cross-sectional study. Pain characteristics, other factors influencing pain, health care-related data and health-related quality of life were summarized and compared among 3 groups of patients according to the type of pain (nociceptive, neuropathic, or mixed), as assigned by the investigators after considering the pathophysiological mechanisms involved. RESULTS: Pain was of mixed pathophysiology in most patients (59.3%; 95% confidence interval [CI], 59.2%-59.5%), followed by nociceptive (31.8%; 95% CI, 31.6%-32.0%) and neuropathic pathophysiology (8.9%; 95% CI, 8.8%-9.1%). Patients with mixed pain had pain in >1 site more frequently than the other groups. Spinal conditions was the attributed cause of pain in >80% of patients with mixed pain, whereas nonspinal osteoarthritis represented almost a third. Patients with mixed pain showed a greater clinical complexity than the remaining patients, as they reflected: more comorbidities, adverse psycho-social factors, health care resource utilization, undertreatment, and perceived difficulties in patient management, but less perceived effectiveness of treatments and a lower health-related quality of life. DISCUSSION: An independent category in the pathophysiological classification of pain is justified based on the differential characteristics of patients with mixed pain, although conceptualization of mixed pain should be improved. Increasing referrals to other specialists or implementing chronic pain management programs would seem advisable. CONCLUSIONS: Patients with mixed pain showed more clinical complexity than patients with other types of pain. The consideration of mixed pain as an independent pathophysiological category may be justifiable on empirical clinical grounds.

Chronic Pain Features Relate to Quality of Life More than Physiopathology: A Cross-Sectional Evaluation in Pain Clinics.

OBJECTIVE: To compare the impact of chronic pain physiopathology on health-related quality of life (HR-QoL), considering the influence of pain features and psychosocial adjustment (intensity, interference, psychological comorbidities, and sleep quality). DESIGN: A cross-sectional study involving 1,025 noncancer patients with predominantly neuropathic, nociceptive, or mixed chronic pain conditions was conducted in 88 pain clinics within Spain. The EuroQol-5 Dimensions instrument (EQ-5D) was used to measure HR-QoL. The Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), and sleep scale developed for the MOS study (MOS-SQ) were used to measure pain features and psychosocial adjustment. Multivariate analyses were used to model HR-QoL measures. RESULTS: All patients reported very low HR-QoL. The mean EQ-5D index scores were 0.33, 0.36, and 0.37 in the mixed, neuropathic, and nociceptive pain groups, respectively. The differences did not reach statistical significance (P = 0.057). Patients with nociceptive pain had less pain (least pain intensity score: 4.7 vs. 5.2 in the other groups; P = 0.006), less interference with daily activities (BPI average interference score: 6.3 vs. 6.6 and 6.7 in the neuropathic and mixed pain groups, respectively; P = 0.013), less anxiety (HADS score: 8.5 vs. 9.6 and 9.7 in the same respective groups; P = 0.001), and fewer sleep problems (MOS-SQ sleep problems index: 46.8 vs. 52.2 and 50.2 in the same respective groups; P = 0.005). In the adjusted analyses, HR-QoL measures were explained by pain intensity, anxiety, and sleep quality, but not by physiopathological pain type. CONCLUSIONS: Pain features, particularly intensity, have a greater impact than pain physiopathology on HR-QoL. Distinct physiopathological mechanisms give rise to different pain features that, in turn, may mediate the HR-QoL of patients with chronic pain. This could be used to improve pain management strategies.