Long-term outcome of implants exhibiting buccal soft tissue dehiscence in the esthetic zone.

OBJECTIVE: Increasing aesthetic demands require that the color and contour of the peri-implant soft tissues be in harmony with the neighboring teeth. Recession, migration toward the apical, is a frequent clinical finding. Its presence can lead to inflammation and increased marginal bone loss. These complications, in addition to affecting the aesthetic results of our treatment, are difficult to treat and can threaten the survival of the implant. There are fewer studies showing the outcome of treatment of soft-tissue defects around implants. The aim of this article is to describe the treatment of a soft-tissue defect around an implant-supported prosthesis treatment, performed on two neighboring implants, in the esthetic zone in a patient with a high smile and to evaluate both the coverage achieved and the patient's esthetic satisfaction. CLINICAL CONSIDERATIONS: This study showed that a mucogingival approach, using a surgical technique designed for the treatment of alveolar ridge defects, together with tissue management with temporaries and a new restoration, achieved an optimal result. CONCLUSIONS: The case has been closely followed up, for 10 years, and the authors have been able to confirm the long-term stability of the result. CLINICAL SIGNIFICANCE: The following paper shows the result of an innovative approach. Connective tissue platform technique, usually performed for soft-tissue augmentation, was used for a defect in soft-tissue dehiscence. The authors followed the results for 10 years, and the results achieved were satisfactory in terms of esthetic.

Surgical complications comparing extraperitoneal vs transperitoneal laparoscopic aortic staging in early stage ovarian and endometrial cancer.

OBJECTIVE: To determine whether the extraperitoneal approach for paraaortic staging lymphadenectomy results in a lower rate of surgical complications compared to the transperitoneal approach, without compromising oncological outcomes. METHODS: Prospective randomized multicenter study of patients with early endometrial or ovarian cancer undergoing paraaortic lymphadenectomy in 2010-2019. Patients were randomized to minimally invasive surgery (laparoscopy or robotic-assisted) using an extraperitoneal or a transperitoneal approach. The primary end point measure was a composite outcome that included developing one or more of the following surgical complications: bleeding during paraaortic lymphadenectomy ≥500 mL, any intraoperative complication related to paraaortic lymphadenectomy, severe postoperative complication (Dindo ≥ IIIA), impossibility to complete the procedure, or conversion to laparotomy. RESULTS: There were 103 patients in the extraperitoneal group and 100 in the transperitoneal group. Differences in the composite outcome (transperitoneal 26.0% vs, extraperitoneal 18.4%; P = 0.195) were not found. Differences in the operative time, conversion to laparotomy, intraoperative bleeding, or survival were not observed. A higher number of lymph nodes were retrieved through the extraperitoneal approached (median, interquartile range [IQR] 12 [7-17] vs, 14 [10-19]: P = 0.026). Older age and greater body mass index (BMI) or waist-to-hip ratio (WHR) increased the risk for surgical complications independently of the laparoscopic approach. CONCLUSIONS: The extraperitoneal approach did not show differences regarding surgical and oncological parameters compared with the transperitoneal approach, although the number of aortic nodes retrieved was higher. The decision to use one or another laparoscopic route is a matter of the surgeon preference. Trial registration ClinicalTrials.gov.identifier: NCT02676726.

Robot-assisted Extraperitoneal Para-aortic Lymphadenectomy Is Associated with Fewer Surgical Complications: A Post Hoc Analysis of the STELLA-2 Randomized Trial.

STUDY OBJECTIVE: To evaluate if extraperitoneal para-aortic lymphadenectomy (PALND) using a robot-assisted approach was associated with fewer complications than all other approaches (conventional laparoscopic transperitoneal or extraperitoneal and robot-assisted transperitoneal) without compromising lymph node yield, operative time, or length of stay. DESIGN: Post hoc analysis of the prospective randomized open-label multicenter trial (STELLA-2). SETTING: Three academic referral hospitals. PATIENTS: Two hundred and three eligible patients from the STELLA-2 trial were included. INTERVENTIONS: The patients were randomized to extraperitoneal or transperitoneal PALND using a minimally invasive approach (either laparoscopic or robot-assisted) for surgical staging of endometrial or ovarian cancer. The minimally invasive approaches were not subjected to randomization. MEASUREMENTS AND MAIN RESULTS: The primary end point was evaluated through a composite variable that included at least 1 of the following events: blood loss ≥500 mL during PALND, any intraoperative complication related to PALND, severe postoperative complication (Clavien-Dindo ≥grade IIIA), impossibility of completing the procedure, or conversion to laparotomy. Of the 203 patients analyzed, 68 were assigned to the extraperitoneal laparoscopic group (X-L), 62 to the transperitoneal laparoscopic group (T-L), 35 to the extraperitoneal robotic group (X-R), and 38 to the transperitoneal robotic group (T-R). A reduced trend in complications was observed in the extraperitoneal robot-assisted arm when considering the primary end point (X-L: 25.0%, T-L: 24.2%, X-R: 5.7%, T-R: 28.9%; p = .073). In a multivariable analysis, age (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00-1.09), body mass index (OR 1.09; 95% CI, 1.03-1.16), and waist-to-hip ratio (OR 1.66; 95% CI, 1.12-2.47) were found to independently increase the risk of PALND complications, whereas the extraperitoneal robotic approach (OR 0.13; 95% CI, 0.02-0.64) was an independent protective factor for complication occurrence. CONCLUSION: Robot-assisted extraperitoneal PALND is associated with fewer surgical complications, without compromising lymph node retrieval, operative time, or length of stay. Robot-enhanced 3D visualization, surgeon ergonomics, or hemostatic precision could explain our results.

Deprescribing of non-antiretroviral therapy in HIV-infected patients.

PURPOSE: In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. METHODS: Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. RESULTS: There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. CONCLUSIONS: The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.

Effectiveness and safety of dual therapy with rilpivirine and boosted darunavir in treatment-experienced patients with advanced HIV infection: a preliminary 24 week analysis (RIDAR study).

BACKGROUND: The objective was to analyze the effectiveness and safety of dual therapy with rilpivirine plus boosted-darunavir (RPV + bDRV) in real-life patients. METHODS: Observational, retrospective, multi-center study in HIV+ patients who had received RPV + bDRV for 24 weeks to optimize/simplify their previous antiretroviral treatment. We determined the percentage of patients without virologic failure (2 consecutive viral loads > 50 copies/mL) at 24 weeks of treatment. RESULTS: The study included 161 patients from 15 hospitals with median age of 49 years; 29.3% had previous AIDS stage and median CD4+ lymphocyte nadir of 170 cells/uL. They had been diagnosed with HIV for a median of 17 years and had received 14 years of ART, with five previous treatment combinations, and 36.6% had a history of virological failure. The reasons for the switch were simplification/optimization (49.7%), toxicity/intolerance (17.4%), or inadequate effectiveness of previous ART (10.6%). Baseline VL of 50-1000 copies/mL was recorded in 25.5% of the patients. In the"intention-to-treat" analysis at 24 weeks, 87.6% of 161 patients continued the study treatment without virologic failure criteria. In the "on treatment" analysis (excluding patients who discontinued treatment with dual therapy for any reason other than virologic failure) the efficacy was 94.6% (141/149 patients). CONCLUSIONS: Dual therapy with RPV + DRVb proved to be effective and safe in patients with advanced HIV infection, long exposure to ART, low CD4 nadir, previous virologic failure, and/or history of ineffective ART.

Epidemiological and clinical characteristics of Streptococcus tigurinus endocarditis.

BACKGROUND: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS. METHODS: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol. RESULTS: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species. CONCLUSIONS: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.

Vaginal Intraepithelial Neoplasia: Clinical Presentation, Management, and Outcomes in Relation to HIV Infection Status.

OBJECTIVES: The data available on vaginal intraepithelial neoplasia (VAIN) and infection by HIV are scarce. We therefore aimed to review the clinical presentation, management, and survival outcomes of VAIN in this group of women. MATERIALS AND METHODS: This is an observational cohort study of women diagnosed with VAIN for a 23-year period. Clinical characteristics and outcomes were analyzed according to women's HIV infection status. Disease-free and progression-free survival were compared between groups. RESULTS: Twenty-two of 87 women were HIV positive (25.3%) compared with the HIV-negative group, HIV-positive women were younger (median age = 39 vs 57 years, p < .001) and more frequently smokers (p < .001). They also presented with multifocal and multicentric disease more often (p = .004 and p = .033, respectively) in relation to infection by human papillomavirus. All HIV-positive women were receiving antiretroviral treatment. The median time from the diagnosis of HIV to the development of VAIN was 14 years (range = 1-22 years). There were no significant differences in survival outcomes between groups. CONCLUSIONS: HIV-positive women are at an increased risk of developing VAIN and frequently present at a younger age with multifocal and multicentric disease. Vaginal intraepithelial neoplasia lesions can develop many years after the initial diagnosis of HIV infection reason why prolonged surveillance is essential to enable prompt diagnosis and treatment.

Costs and cost-efficacy analysis of the 2016 GESIDA/Spanish AIDS National Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults.

INTRODUCTION: GESIDA and the AIDS National Plan panel of experts suggest preferred (PR), alternative (AR), and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for the year 2016. The objective of this study is to evaluate the costs and the efficacy of initiating treatment with these regimens. METHODS: Economic assessment of costs and efficiency (cost/efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48 in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and the costs correspond to those of 2016. A sensitivity deterministic analysis was conducted, building three scenarios for each regimen: base case, most favourable, and least favourable. RESULTS: In the base case scenario, the cost of initiating treatment ranges from 4663 Euros for 3TC+LPV/r (OR) to 10,894 Euros for TDF/FTC+RAL (PR). The efficacy varies from 0.66 for ABC/3TC+ATV/r (AR) and ABC/3TC+LPV/r (OR), to 0.89 for TDF/FTC+DTG (PR) and TDF/FTC/EVG/COBI (AR). The efficiency, in terms of cost/efficacy, ranges from 5280 to 12,836 Euros per responder at 48 weeks, for 3TC+LPV/r (OR), and RAL+DRV/r (OR), respectively. CONCLUSION: Despite the overall most efficient regimen being 3TC+LPV/r (OR), among the PR and AR, the most efficient regimen was ABC/3TC/DTG (PR). Among the AR regimes, the most efficient was TDF/FTC/RPV.

Combination of Thrombolysis and Statins in Acute Stroke Is Safe: Results of the STARS Randomized Trial (Stroke Treatment With Acute Reperfusion and Simvastatin).

BACKGROUND AND PURPOSE: The STARS trial (Stroke Treatment With Acute Reperfusion and Simvastatin) was conducted to demonstrate the efficacy and safety of simvastatin treatment in acute stroke. METHODS: STARS07 was a multicentre, phase IV, prospective, randomized, double-blind, placebo-controlled trial. Patients with Acute ischemic stroke recruited within 12 hours from symptom onset were randomized to oral simvastatin 40 mg or placebo, once daily for 90 days. Primary outcome was proportion of independent patients (modified Rankin Scale score of ≤2) at 90 days. Safety end points were hemorrhagic transformation, hemorrhagic events, death, infections, and serious adverse events. RESULTS: From April 2009 to March 2014, 104 patients were included. Fifty-five patients received intravenous tissue-type plasminogen activator. No differences were found between treatment arms regarding the primary outcome (adjusted odds ratio, 0.99 [0.35-2.78]; P=0.98). Concerning safety, no significant differences were found in the rate of hemorrhagic transformation of any type, nor symptomatic hemorrhagic transformation. There were no differences in other predefined safety outcomes. In post hoc analyses, for patients receiving tissue-type plasminogen activator, a favorable effect for simvastatin treatment was noted with higher proportion of patients experiencing major neurological recovery (adjusted odds ratio, 4.14 [1.18-14.4]; P=0.02). CONCLUSIONS: Simvastatin plus tissue-type plasminogen activator combination seems safe in acute stroke, with low rates of bleeding complications. Because of the low recruitment, the STARS trial was underpowered to detect differences in simvastatin efficacy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01073007.

Prospective Randomized Trial Comparing Transperitoneal Versus Extraperitoneal Laparoscopic Aortic Lymphadenectomy for Surgical Staging of Endometrial and Ovarian Cancer: The STELLA Trial.

BACKGROUND: There is an ongoing debate on which approach, transperitoneal or extraperitoneal, is superior for the performance of laparoscopic aortic lymphadenectomy (LPA-LND) for the surgical staging of gynecologic cancer. A prospective randomized trial (STELLA trial) was designed to compare the perioperative outcomes and node retrieval of extraperitoneal versus transperitoneal aortic lymphadenectomy by laparoscopy or robot-assisted laparoscopy. METHODS: Patients with endometrial or ovarian carcinoma requiring aortic lymphadenectomy for surgical staging were randomized to an extraperitoneal or transperitoneal approach by laparoscopy or robot-assisted laparoscopy between June 2012 and July 2014. RESULTS: A total of 60 patients were entered into the study, 48 with endometrial cancer (80 %) and 12 with ovarian cancer (20 %). Thirty-one patients (51.6 %) were randomly assigned to the extraperitoneal group and 29 to the transperitoneal group (48.3 %). The means LPA-LND operating time was 90 min in both group (p = 0.343). The mean (range) blood loss was 105 (10-400) mL for extraperitoneal versus 100 (5-1000) mL for transperitoneal group (p = 0.541). There were no differences in the number of collected lymph nodes between the two groups [median (range) for extraperitoneal 12 (4-41) vs. 13 (4-29) for transperitoneal (p = 0.719)]. CONCLUSIONS: The extraperitoneal and transperitoneal approaches for laparoscopic and robotic aortic lymphadenectomy provide similar perioperative outcomes and nodal yields. TRIAL REGISTRATION: The STELLA trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT01810874.

Factors related to NT-proBNP levels in HIV patients aged over 40 years.

OBJECTIVE: To determine the levels of NT-pro BNP in HIV patients over 40 years who are receiving highly active antiretroviral therapy (HAART) and investigating potential independent clinical or laboratory factors. METHOD: We determine levels of NT-pro BNP in peripheral blood of HIV patients from Costa del Sol Hospital, over 40 years. We collected epidemiological, classical cardiovascular risk factors and variables associated with HIV infection status. The qualitative variables were compared using the χ2 test. NT-proBNP levels were taken as the dependent variable. The association between these levels and the quantitative variables were studied by analysis of variance (ANOVA), and the association with the qualitative variables, using Student's t test. RESULTS: Nt-pro BNP levels were determined in 146 HIV patients. We assess the 10-year cardiovascular risk calculated by the Framingham equation, 59 (41.5%) were classified as low risk, 46 (32.4%) as a moderate risk and 37 (26.1%) as a high risk. The higher levels of NT-pro BNP were found in women, and in those patient with lower filtration rate and high levels of triglycerides. An association was also observed between higher levels of NT-proBNP and the recent use of lamivudine and fosamprenavir. After a multivariate analysis we found an association between higher levels of NT-proBNP and the current use of fosamprenavir and a lower glomerular filtration rate. CONCLUSIONS: We found, with the limitations of a small serie, that higher levels of NTproBNP in HIV patients could be linked to the occurrence of cardiovascular events, this fact suggest that NTpro BNP could be used in patients at moderate or high vascular risk in order to optimise the primary prevention of vascular events.

Changes in Quality of Life after 3 months of Usual Care in a Large Sample of Patients with Noncancer Pain: The "QOOL: Quality of Life and Pain" Study.

Large-scale observational studies can provide useful information on changes in health outcomes over time. The aim of this study was to investigate the effect of 3 months of usual care on quality of life (QOL) and pain outcomes in noncancer chronic pain patients managed by pain specialists and to examine factors associated with changes in QOL. This was assessed using the EQ-5D and pain outcomes using the Brief Pain Inventory (BPI). Changes in QOL and pain were studied for the overall sample and in subgroups defined by baseline pain severity. Multivariate regression was used to investigate factors associated with change on EQ-5D. Three thousand and twenty-nine patients were included for analysis. After 3 months of usual care, a mean of 40.9% of patients showed improvement on individual EQ-5D dimensions, with the highest rates of improvement seen on the pain/discomfort (50.8%) and anxiety/depression (48.3%) dimensions. The EQ-5D Index increased from a mean (SD) of 0.35 (0.2) to 0.58 (0.21) points between baseline and month 3, and the thermometer from 41.5 (19.4) to 58.7 (17.8), indicating a large effect. Improvements in QOL were larger in those with severe baseline pain. The BPI severity summary score improved from a mean (SD) of 6.5 (1.4) to 4.1 (1.7) and the interference summary score from 6.6 (1.5) to 4.2 (1.9). Changes on the BPI severity and interference scores were associated with changes in the EQ-5D Index and thermometer. In conclusion, 3 months of usual care in noncancer pain patients led to substantial improvements in QOL and pain outcomes.

Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treating enterococcus faecalis infective endocarditis.

BACKGROUND: The aim of this study was to compare the effectiveness of the ampicillin plus ceftriaxone (AC) and ampicillin plus gentamicin (AG) combinations for treating Enterococcus faecalis infective endocarditis (EFIE). METHODS: An observational, nonrandomized, comparative multicenter cohort study was conducted at 17 Spanish and 1 Italian hospitals. Consecutive adult patients diagnosed of EFIE were included. Outcome measurements were death during treatment and at 3 months of follow-up, adverse events requiring treatment withdrawal, treatment failure requiring a change of antimicrobials, and relapse. RESULTS: A larger percentage of AC-treated patients (n = 159) had previous chronic renal failure than AG-treated patients (n = 87) (33% vs 16%, P = .004), and AC patients had a higher incidence of cancer (18% vs 7%, P = .015), transplantation (6% vs 0%, P = .040), and healthcare-acquired infection (59% vs 40%, P = .006). Between AC and AG-treated EFIE patients, there were no differences in mortality while on antimicrobial treatment (22% vs 21%, P = .81) or at 3-month follow-up (8% vs 7%, P = .72), in treatment failure requiring a change in antimicrobials (1% vs 2%, P = .54), or in relapses (3% vs 4%, P = .67). However, interruption of antibiotic treatment due to adverse events was much more frequent in AG-treated patients than in those receiving AC (25% vs 1%, P < .001), mainly due to new renal failure (≥25% increase in baseline creatinine concentration; 23% vs 0%, P < .001). CONCLUSIONS: AC appears as effective as AG for treating EFIE patients and can be used with virtually no risk of renal failure and regardless of the high-level aminoglycoside resistance status of E. faecalis.

The surgical management of early-stage cervical cancer.

PURPOSE OF REVIEW: The main objective is to update the literature data in the last year which may support a surgical approach to early cervical cancer [ECC; Stage International Federation of Gynecology and Obstetrics (FIGO) IA-IB1-IIA1]. Radical hysterectomy remains the gold standard by most international guidelines because surgical treatment has hardly changed in recent decades, except for stage IA1. RECENT FINDINGS: Trends in clinical research in the past 12-18 months involve minimal invasive surgery (with laparoscopic surgery or robotic-assisted surgery), fertility preservation (in the initial stages and in the absence of bad prognostic factors), nerve-sparing and sentinel node techniques. Some institutions have published studies in specific groups such as older, obese or pregnant women. SUMMARY: There is a growing trend to practice less aggressive surgery in order to preserve fertility in young women and avoid an excess of treatment in some selected patients. Therefore, nerve-sparing techniques can help to improve the quality of life. More studies are needed to demonstrate oncologic results of the sentinel node technique. Laparoscopic and robotic-assisted surgery can substitute open surgical treatment.

Vaccination trends in people with HIV infection participanting in the hospital-based survey of patients infected with HIV, 2006-2021.

OBJECTIVE: To assess the trend in hepatitis A, hepatitis B, pneumococcal, tetanus and seasonal influenza vaccination in people with HIV infection and to analyse associated factors. METHODS: The Hospital Survey of Patients with HIV, an annual cross-sectional study conducted on a fixed day (2006-2021), was used. Inpatients and outpatients were included. Trends in vaccination and associated factors were analysed using logistic regression. RESULTS: A total of 8643 participants were included. Vaccination rates increased to 65.3% for hepatitis A, 83.7% for hepatitis B, 49.3% for tetanus, 68.9% for pneumococcal and 74.5% for seasonal influenza in 2021. Factors positively associated with vaccination were older age for pneumococcal and influenza vaccination; higher educational level for hepatitis A and tetanus; living in a closed institutions or prison for tetanus, pneumococcal and influenza; and having acquired HIV through sex between men for hepatitis A, B and pneumococcal. In addition, being on antiretroviral treatment and having a high CD4 count were positively associated with vaccination for all these diseases. Factors inversely associated with vaccination were being older (hepatitis A, B and tetanus), being an immigrant (tetanus and seasonal influenza) and being an injection drug user/ex-user for hepatitis A and B. CONCLUSIONS: Vaccination in people with HIV has increased in the study period. The results are in line with the recommendations in this population, although there is still room to reach the established vaccination indicators.

Safety and efficacy of intra-arterial bone marrow mononuclear cell transplantation in patients with acute ischaemic stroke in Spain (IBIS trial): a phase 2, randomised, open-label, standard-of-care controlled, multicentre trial.

BACKGROUND: Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke. METHODS: The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18-80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1-7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6-20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed. FINDINGS: Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9-15), with intra-arterial BMMNC injection done a median of 6 days (4-7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55-7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52-6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72-6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group. INTERPRETATION: Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints. FUNDING: Instituto de Salud Carlos III co-funded by the European Regional Development Fund/European Social Fund, Mutua Madrileña, and the Regional Ministry of Health of Andalusia.

Seroprevalence of antibodies to the influenza A (H1N1) virus among healthcare workers prior to the 2009 pandemic peak.

OBJECTIVE: Our aim was to study the proportion of healthcare workers with a positive serology for Influenza A(H1N1)2009 without having flu, in a Spanish hospital at the beginning of the pandemic. METHODS: A survey study carried out during August 2009 (before the peak of the pandemic in Spain) in the Hospital Costa del Sol, a second level hospital with almost 300 beds in the South of Spain. The participants were workers in the following hospital units: Emergencies, Medical Area (Internal Medicine, Chest Diseases), Surgical Area (General Surgery and Anaesthesia) of any professional category. A study was made of the proportion of healthcare workers in our hospital with positive serology for the new influenza A (H1N1)2009 virus, as determined by the haemagglutination inhibition technique (≥1/40). The subjects completed a health status questionnaire, and provided a blood sample for serology testing. RESULTS: A total of 239 workers participated, of whom 25.1% had positive serology. The hospital area in which most individuals had positive serology was the Emergency Department (36.6%), while the professional category in which most individuals with a positive serology worked was that of the orderlies (41.7%). CONCLUSION: Around 25% of healthcare workers in our hospital had positive serology before the peak of the pandemic, none of them had received vaccine for Influenza A (H1N1) 2009 or had been diagnosed of influenza previously.

Influence of sociodemographic factors upon pain intensity in patients with temporomandibular joint disorders seen in the primary care setting.

OBJECTIVE: A study is made of the influence of gender, educational level, marital status, income, social support, and perceived general and oral health upon pain intensity in a sample of patients with temporomandibular joint disorders (TMJD) explored in primary care (AP). DESIGN: A review was made of 899 patients from Córdoba Healthcare District (Spain) referred to the primary care TMJD Unit by their primary care physician and/or dentist. Of these subjects, 151 failed to meet the inclusion criteria. The remaining 748 subjects were explored according to the corresponding research diagnostic criteria (RDC/TMJD). A bivariate analysis was made the association of pain intensity to the demographic and psychological characteristics of the patients, and to perceived general and oral health, followed by a multivariate linear regression analysis to explain pain intensity as a function of the rest of the variables. The SPSS version 19.0 statistical package was used. RESULTS: The patient age ranged from 18-86 years, with a mean of 45.8 years (± 15.8), and a female predominance of 5:1. The characteristic pain intensity (CPI) score was almost 15 points higher on average in women than in men (p<0.05). A lower educational level, and separation or divorce, were correlated to an increased intensity of pain. Social support, depression and general and oral health also explained part of pain intensity. The regression model established with these variables accounted for 13.3% of the variability of pain (R2 = 0.133). CONCLUSIONS: Women suffer more intense pain than men. Perceived health partially explains the variability of the CPI score. However, it is empirically seen that the variables gender, educational level and marital status exert an important and independent influence upon pain intensity.

Genetic and functional homologous repair deficiency as biomarkers for platinum sensitivity in TNBC: A case report.

Triple-negative breast cancer is the most aggressive subtype of mammary carcinoma. In the early stage, neoadjuvant chemotherapy (NAC) is the standard of care for prognostic stratification and the best adjuvant treatment strategy. A 30-year-old female presented in the emergency room because of a gigantic right breast associated with an ulcerated lump at the upper quadrants. The right axillary nodes were palpable. An ultrasound was performed, showing the ulcerated neoformation with enlarged right axillary lymph nodes observed to level III. A core biopsy of the breast lesion was performed, and the pathological examination revealed a nonspecial type, grade 3, invasive, triple-negative breast cancer. No distant disease was found in the PET-CT scan. A germline genetic panel by next-generation sequencing identified a likely pathogenic variant in RAD51D (c.898C>T). Assessment of the functionality of the DNA homologous recombination repair pathway by RAD51 foci in the tumor revealed a profile of homologous recombination deficiency. NAC consisting of weekly carboplatin and paclitaxel followed by dose-dense doxorubicin/cyclophosphamide was performed with a complete metabolic response achieved in the PET-CT scan. The patient underwent a modified radical mastectomy plus axillary lymphadenectomy with a pathological complete response in the breast and axilla and remains disease-free after 2 years of follow-up. We report a young female with a triple-negative breast cancer stage cT4bN3M0 and a hereditary pathogenic mutation in RAD51D. The tumor was highly proliferative and homologous recombination-deficient by RAD51. The patient received platinum-based NAC, achieving a pathologic complete response. More effort should be made to identify predictive functional biomarkers of treatment response, such as RAD51 foci, for platinum sensitivity.

[Left-sided endocarditis due to gram-negative bacilli: epidemiology and clinical characteristics]. / Endocarditis sobre válvulas izquierdas por bacilos gran negativos: epidemiología y características clínicas.

INTRODUCTION: The aim of this study is to describe the epidemiological, clinical characteristics, and outcome of patients with left-side endocarditis caused by gram-negative bacteria. METHOD: Prospective multicenter study of left-sided infective endocarditis reported in the Andalusian Cohort for the Study of Cardiovascular Infections between 1984 and 2008. RESULTS: Among the 961 endocarditis, 24 (2.5%) were caused by gram-negative bacilli. The most common pathogens were Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica. Native valves (85.7%) were mainly affected, most of them with previous valve damage (57%). Comorbidity was greater (90% vs 39%; P=.05) than in endocarditis due to other microorganism, the most frequent being, diabetes, hepatic cirrhosis and neoplasm. A previous manipulation was found in 47.6% of the cases, and 37% were considered hospital-acquired. Renal failure (41%), central nervous system involvement (33%) and ventricular dysfunction (45%) were the most frequent complications. Five cases (21%) required cardiac surgery, mostly due to ventricular dysfunction. More than 50% of cases were treated with aminoglycosides, but this did not lead to a better outcome or prognosis. Mortality (10 patients) was higher than that reported with other microorganisms (41% vs 35%; P=.05). CONCLUSIONS: Left-sided endocarditis due to gram-negative bacilli is a rare disease, which affects patients with major morbidities and often with a previous history of hospital manipulations. Cardiac, neurological and renal complications are frequent and associated with a high mortality. The association of aminoglycosides in the antimicrobial treatment did not involve a better outcome or prognosis.