Real-life data of immune recovery using bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed people living with HIV. Results at 48-96†weeks of RETROBIC Study.

BACKGROUND: Switching strategy with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) has become a gold standard for people living with HIV (PLWH), achieving high efficacy and safety rates. However, data regarding immune status in long-term real-life cohorts of pretreated patients are needed. METHODS: We performed a multicentre, non-controlled, retrospective study in virologically suppressed PLWH switching to B/F/TAF. We evaluated CD4+, CD8+ and CD4+/CD8+ ratio, efficacy and safety at weeks 48 and 96. RESULTS: The study comprised 1966 PLWH from 12 hospitals in Spain, of whom 80% were men, and the median age was 51.0 [42.0-57.0] years. The median time of HIV infection was 18.0 [10.0-27.0] years. No significant changes in CD4+, CD8+ T cells, or CD4+/CD8+ were observed after 96 weeks. Nevertheless, in women at weeks 48 and 96, we found a significant increase of CD4+ T cells and a significant decrease in CD8+ T cells. In patients ≥60 years at week 96, CD4 T cells significantly increased and CD8+ T cells significantly decreased at week 48. The on-treatment analysis revealed HIV-RNA <50 copies/mL in 95.6% (1700/1779) and 96.7% (1312/1356) of patients at weeks 48 and 96, respectively. The rates increased to 99.2% (1765/1779) and 99.7% (1352/1356) when considering HIV-RNA <200 copies/mL. No resistance mutations were detected in virologic failures. B/F/TAF discontinuations accounted for 10.2% (200). Simplification was the most common reason for discontinuation in 3.8% (74) of patients. CONCLUSION: In long-term virologically controlled PLWH, B/F/TAF achieved high efficacy rates and slightly improved immune status in women and individuals aged 60 and over after 48 and 96 of switching.

Differences in the inflammatory response among hospitalized patients with distinct variants of SARS-CoV-2.

The SARS-CoV-2 variants demonstrate diverse transmission patterns, modifications in infectivity, and immune response. Changes in disease manifestation may be attributed to vaccination and the virus's reduced capacity to induce inflammation. Objectives: To investigate the relationship between the inflammatory response and the characteristics of COVID-19 across successive waves. Methods: A retrospective cross-sectional study was conducted to evaluate sociodemographic, clinical, and laboratory data of Alpha (G1), Delta (G2), and Omicron (G3) variants. Results: A total of 300 patients from a hospital in Madrid, Spain, were included. The groups exhibited similar sociodemographic and baseline characteristics. The Alpha variant predominantly affected younger patients, while the Omicron variant affected patients with a higher prevalence of comorbidities. The Alpha group had the lowest vaccination rate compared to the highest rate in the Omicron group. The Alpha group received a higher proportion of tocilizumab compared to the other groups. Despite these differences, the severity scores were similar among the three variants. Regarding laboratory parameters, differences were observed in haemoglobin, D-dimer, alkaline phosphatase, and potassium levels. The Omicron variant showed higher D-dimer levels (p=0.04). In the multivariate analysis, differences in leukocyte count, haemoglobin, alkaline phosphatase, and potassium levels were consistently observed among patients from different waves. Omicron exhibited a higher absolute leukocyte count than the Alpha variant (p=0.003). Conclusion: No significant differences were found in inflammation biomarkers among the three variants. Furthermore, there were no significant disparities in mortality or disease severity. The level of inflammatory response in patients may be determined by the severity of COVID-19, rather than the specific viral variant.

Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS events.

BACKGROUND: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. METHODS: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. FINDINGS: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95% CI 1.03-2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95% CI 1.57-6.07). Additionally, low CD4 count at cut-offs of <500 cells/µL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500 cells/µL, a CD8 count ≥1500 cells/µL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk. INTERPRETATION: Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/µL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions. FUNDING: This work was supported by CIBER (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU; by the Spanish AIDS Research Network (RIS) RD16/0025/0001 project as part of the Plan Nacional R + D + I, and cofinanced by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), ISCIII projects PI18/00154, PI21/00141, and ERDF, "A way to make Europe", ICI20/00058.

Specific Cellular and Humoral Immune Responses to the Neoantigen RBD of SARS-CoV-2 in Patients with Primary and Secondary Immunodeficiency and Healthy Donors.

Patients with antibody deficiency disorders, such as primary immunodeficiency (PID) or secondary immunodeficiency (SID) to B-cell lymphoproliferative disorder (B-CLPD), are two groups vulnerable to developing the severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). The data on adaptive immune responses against SARS-CoV-2 are well described in healthy donors, but still limited in patients with antibody deficiency of a different cause. Herein, we analyzed spike-specific IFN-γ and anti-spike IgG antibody responses at 3 to 6 months after exposure to SARS-CoV-2 derived from vaccination and/or infection in two cohorts of immunodeficient patients (PID vs. SID) compared to healthy controls (HCs). Pre-vaccine anti-SARS-CoV-2 cellular responses before vaccine administration were measured in 10 PID patients. Baseline cellular responses were detectable in 4 out of 10 PID patients who had COVID-19 prior to vaccination, perceiving an increase in cellular responses after two-dose vaccination (p < 0.001). Adequate specific cellular responses were observed in 18 out of 20 (90%) PID patients, in 14 out of 20 (70%) SID patients and in 74 out of 81 (96%) HCs after vaccination (and natural infection in some cases). Specific IFN-γ response was significantly higher in HC with respect to PID (1908.5 mUI/mL vs. 1694.1 mUI/mL; p = 0.005). Whereas all SID and HC patients mounted a specific humoral immune response, only 80% of PID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC patients (p = 0.040), without significant differences between PID and HC patients (p = 0.123) and between PID and SID patients (p =0.683). High proportions of PID and SID patients showed adequate specific cellular responses to receptor binding domain (RBD) neoantigen, with a divergence between the two arms of the adaptive immune response in PID and SID patients. We also focused on the correlation of protection of positive SARS-CoV-2 cellular response to omicron exposure: 27 out of 81 (33.3%) HCs referred COVID-19 detected by PCR or antigen test, 24 with a mild course, 1 with moderate symptoms and the remaining 2 with bilateral pneumonia that were treated in an outpatient basis. Our results might support the relevance of these immunological studies to determine the correlation of protection with severe disease and for deciding the need for additional boosters on a personalized basis. Follow-up studies are required to evaluate the duration and variability in the immune response to COVID-19 vaccination or infection.

Monitoring monkeypox virus in saliva and air samples in Spain: a cross-sectional study.

BACKGROUND: The transmission of monkeypox virus occurs through direct contact, but transmission through saliva or exhaled droplets and aerosols has not yet been investigated. We aimed to assess the presence of monkeypox virus DNA and infectious virus in saliva samples and droplets and aerosols exhaled from patients infected with monkeypox virus. METHODS: We did a cross-sectional study in patients with monkeypox confirmed by PCR who attended two health centres in Madrid, Spain. For each patient, we collected samples of saliva, exhaled droplets within a mask, and aerosols captured by air filtration through newly developed nanofiber filters. We evaluated the presence of monkeypox virus in the samples by viral DNA detection by quantitative PCR (qPCR) and isolation of infectious viruses in cell cultures. FINDINGS: Between May 18 and July 15, 2022, 44 patients with symptomatic monkeypox attended two health centres in Madrid and were included in the study. All were cisgender men, with a median age of 35·0 years (IQR 11·3). We identified high loads of monkeypox virus DNA by qPCR in 35 (85%) of 41 saliva samples. Infectious monkeypox virus was recovered from 22 (67%) of 33 saliva samples positive for monkeypox virus DNA. We also found a significant association between the number of affected cutaneous areas or general symptoms and the viral load present in saliva samples. Droplets exhaled from patients with monkeypox, detected inside a mask, contained monkeypox virus DNA in 32 (71%) of 45 samples, with two of the 32 positive samples showing the presence of the infectious virus. Monkeypox virus DNA in aerosols, collected from the medical consultation room, were detected in 27 (64%) of 42 samples, despite patients wearing an FFP2 mask during the visit. Infectious virus was not recovered from aerosol samples. High levels of monkeypox virus DNA were identified in aerosols collected from a hospital isolation room housing a patient with monkeypox. INTERPRETATION: The identification of high viable monkeypox virus loads in saliva in most patients with monkeypox and the finding of monkeypox virus DNA in droplets and aerosols warrants further epidemiological studies to evaluate the potential relevance of the respiratory route of infection in the 2022 monkeypox virus outbreak. FUNDING: EU, Consejo Superior de Investigaciones Científicas, and Ciberinfec.

Use of Tenofovir Alafenamide/Emtricitabine/Elvitegravir-Cobicistat in HIV-Naive Patients with Advanced Disease: GENIS Study.

Objective: The primary endpoint of the study was to determine the proportion of patients with HIV RNA < 50 copies/mL at 48 weeks. Design: Phase IV, multicentric, open-label, single-arm clinical trial of participants recruited in 2018−2019 to evaluate the efficacy and safety of tenofovir alafenamide/emtricitabine/elvitegravir-cobicistat (TAF/FTC/EVG-c) as first-line treatment in HIV-1 infected naïve participants with advanced disease. Methods: Adverse events were graded according to the Division of AIDS scale version 2.0. Quantitative variables were recorded as median and interquartile range, and qualitative variables as absolute number and percentage. T-Student or Wilcoxon tests were used to analyze intragroup differences of the continuous variables. Results: Fifty participants were recruited with a baseline median CD4 lymphocyte count of 116 cells/µL and a viral load of 218,938 copies/mL. The proportion of patients with viral load <50 copies/mL at week 48 was 94% in the per-protocol analysis, with a median time of 1.9 months to achieve it. Three adverse events attributed to the study drug caused trial discontinuation. Conclusions: the use of TAF/FTC/EVG-c in patients with advanced HIV disease in our study demonstrated efficacy comparable to data from pivotal clinical trials with a good safety profile.

Monkeypox outbreak in Madrid (Spain): Clinical and virological aspects.

BACKGROUND: Monkeypox is the most prevalent Orthopoxvirus zoonosis infection since the eradication of smallpox. The current multi-country outbreak involves five WHO regions affecting mainly Europe. Accurate clinical and virological aspects of the disease outside endemic areas are needed. METHODS: We performed an observational study of cases diagnosed in Madrid (Spain) (May/June 2022). Confirmation from vesicular lesions swabs, Orthopoxvirus real-time PCR, sequencing, phylogenetic analysis, and direct detection by Electron microscopy was performed. In addition, a structured epidemiological questionnaire was completed systematically to gather sociodemographic, clinical, and behavioral data from all confirmed cases. FINDINGS: We extracted data from 48 patients, all cisgender men. The median age was 35 years (IQR 29 - 44), and 87.5% were MSM. The most prevalent symptoms were the presence of vesicular-umbilicated and pseudo-pustular skin lesions (93.8%), asthenia (66.6%), and fever (52.1%). In addition, the location of the lesions in the genital or perianal area was related to the role in sexual intercourse (p<0.001). Sequencing analysis indicated the virus circulating in Spain belongs to the western African clade. Like the other European cases in the outbreak, the Spanish isolates are a direct descendant of viruses previously detected in Nigeria, the UK, Singapore, and Israel in 2017-2018. CONCLUSIONS: Monkeypox is an emerging infectious disease in Europe where community transmission is reported, mainly in MSM. The first symptom was skin lesions instead of classical fever and rash. The disease follows a self-limited course, and there have been no cases with a serious presentation or severe complications.

Low-dose Radiation Therapy in the Management of COVID-19 Pneumonia (LOWRAD-Cov19). Final results of a prospective phase I-II trial.

BACKGROUND AND PURPOSE: To evaluate the results of low-dose radiation therapy (LD-RT) to lungs in the management of patients with COVID-19 pneumonia. MATERIAL AND METHODS: We conducted a prospective phase I-II trial enrolling COVID-19 patients ≥50 years-old, with bilateral lung involvement at imaging study and oxygen requirement (oxygen saturation ≤93% on room air). Patients received 1 Gy to whole lungs in a single fraction. Primary outcome was a radiological response assessed as severity and extension scores at days +3 and +7. Secondary outcomes were toxicity (CTCAE v5.0), days of hospitalization, changes in inflammatory blood parameters (ferritin, lymphocytes, C-reactive protein, d-dimer and LDH) and SatO2/FiO2 index (SAFI), at day +3 and +7. Descriptive analyses were summarized as means with standard deviation (SD) and/or medians with interquartile ranges (IQR). A Wilcoxon sign rank test for paired data was used to assess the CT scores and Chi Square was used to assess for comparison of categorical variables. RESULTS: Forty-one patients were included. Median age was 71 (IQR 60-84). Eighteen patients (44%) previously received an anti-COVID treatment (tocilizumab, lopinavir/ritonavir, remdesivir) and thirty-two patients (84%) received steroids during LD-RT. The extension score improved significantly (p = 0.02) on day +7. Mean baseline extension score was 13.7 (SD ± 4.9) with a score of 12.2 (±5.2) at day 3, and 12.4 ± 4.7 at day 7. No differences were found in the severity score. SAFI improved significantly on day +3 and +7 (p < 0.01). Median SAFI on day 0 was 147 (IQR 118-264), 230 (IQR 120-343) on day +3 and 293 (IQR 121-353) on day +7. Significant decrease was found in C-reactive protein on day +7 (p = 0.02) and in lymphocytes counts on day +3 and +7 (p = 0.02). The median number of days in hospital after RT was 11 (range 4-78). With a median follow-up of 60 days after LD-RT, 26 (63%) patients were discharged, 11 (27%) died because of COVID respiratory failure and 4 (10%) died of other causes. CONCLUSIONS: LD-RT is a feasible and well-tolerated treatment that could lead to rapid clinical improvement. Large randomized trials would be required to establish the efficacy of LD-RT to treat COVID-19 pneumonia.

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.

Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization.

Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3 treatment-related adverse events observed (hypersensitivity and diarrhea). The discharge rates by Days 8 and 15 were 56.8% and 81.8%, respectively, with data sustaining dose-effect. A mean 4.2 log10 viral load reduction was attained by Day 15. Improvement in inflammation markers was also noted in a seemingly dose-dependent manner. These results suggest that plitidepsin impacts the outcome of patients with COVID-19. ONE-SENTENCE SUMMARY: Plitidepsin, an inhibitor of SARS-Cov-2 in vitro , is safe and positively influences the outcome of patients hospitalized with COVID-19.

Isolation of a Ru(IV) side-on peroxo intermediate in the water oxidation reaction.

The electrons that nature uses to reduce CO2 during photosynthesis come from water oxidation at the oxygen-evolving complex of photosystem II. Molecular catalysts have served as models to understand its mechanism, in particular the O-O bond-forming reaction, which is still not fully understood. Here we report a Ru(IV) side-on peroxo complex that serves as a 'missing link' for the species that form after the rate-determining O-O bond-forming step. The Ru(IV) side-on peroxo complex (η2-1iv-OO) is generated from the isolated Ru(IV) oxo complex (1iv=O) in the presence of an excess of oxidant. The oxidation (IV) and spin state (singlet) of η2-1iv-OO were determined by a combination of experimental and theoretical studies. 18O- and 2H-labelling studies evidence the direct evolution of O2 through the nucleophilic attack of a H2O molecule on the highly electrophilic metal-oxo species via the formation of η2-1iv-OO. These studies demonstrate water nucleophilic attack as a viable mechanism for O-O bond formation, as previously proposed based on indirect evidence.

Low-Dose Radiation Therapy in the Management of Coronavirus Disease 2019 (COVID-19) Pneumonia (LOWRAD-Cov19): Preliminary Report.

PURPOSE: Low-dose radiation therapy (LD-RT) has been shown to have an anti-inflammatory effect, and preliminary results suggest it is feasible to treat patients with coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: We conducted a prospective, single-arm, phase 1/2 clinical trial enrolling patients aged ≥50 years, who were coronavirus disease 2019 (COVID-19) positive, at phase 2 or 3 with lung involvement at imaging study and oxygen requirement. Patients received 100 cGy to total lungs in a single fraction. Primary outcome was radiologic response using severity and extension score on baseline computed tomography (CT), at days 3 and 7 after LD-RT. Secondary outcomes were toxicity using Common Terminology Criteria for Adverse Events v.5.0, duration of hospitalization, blood work evolution, and oxygen requirements using SatO2/FiO2 index (SAFI), at days 3 and 7 after LD-RT. RESULTS: Nine patients were included. Median age was 66 (interquartile range, 57-77). Severity score was stable or decreased in the third CT but was not statistically significant (P = .28); however, there were statistically significant changes in the extension score (P = .03). SAFI index significantly improved 72 hours and 1 week after LD-RT (P = .01). Inflammatory blood parameters decreased 1 week after RT compared with baseline; only lactate dehydrogenase decreased significantly (P = .04). Two patients presented grade 2 lymphopenia after RT and another (with baseline grade 3) worsened to grade 4. Overall, the median number of days of hospitalization was 59 (range, 26-151). After RT the median number of days in the hospital was 13 (range, 4-77). With a median follow-up after RT of 112 days (range, 105-150), 7 patients were discharged and 2 patients died, 1 due to sepsis and the other with severe baseline chronic obstructive pulmonary disease from COVID-19 pneumonia. CONCLUSIONS: Our preliminary results show that LD-RT was a feasible and well-tolerated treatment, with potential clinical improvement. Randomized trials are needed to establish whether LD-RT improves severe pneumonia.

Tolerability of IM penicillin G benzathine diluted or not with local anesthetics, or different gauge needles for syphilis treatment: a randomized clinical trial.

BACKGROUND: Penicillin G Benzathine (PGB) is the cornerstone of syphilis treatment. However, its intramuscular (IM) administration is associated with pain at the site of injection. The dilution of PGB with local anesthetics is recommended in some guidelines, but the evidence that supports it, particularly in adults and in HIV infection, is scarce. Preliminary clinical experience also suggests that the IM administration of PGB through increased needle gauges might improve its tolerability. The aim of the study to identify less painful ways of administering IM PGB in the treatment of syphilis in adults. METHODS: Multicenter, randomized, double-blinded clinical trial in patients diagnosed with primary syphilis that required a single IM injection of PGB 2400,00 IU. Patients were randomized to receive PGB diluted with 0.5 mL mepivacaine 1% (MV) or PGB alone, and both groups either with a long 19G or short 21G IM needle. The primary objective was the effect on local pain immediately after the administration through a visual scale questionnaire on pain (0 to 10). RESULTS: One hundred eight patients were included, 27 in each group. Ninety-four (94.4%) were male, and 41.7% were also HIV-infected. Mean age 36.6 years (SD 11). Significant differences in immediate pain intensity were observed when comparing the long 19G group with anesthesia (mean pain intensity, [MPI] 2.92 [CI 95% 1.08-4.07]) vs long 19G without anesthesia (MPI 5.56 [CI 95% 4.39-6.73), p < 0.001; and also between short 21G group with anesthesia (MPI 3.36 [CI 95% 2.22-4.50]) vs short 21G without anesthesia (MPI 5.06 [CI 95% 3.93-6.19]), p = 0.015). No significant differences in immediate pain were observed between 19G and 21G in the presence or absence of anesthesia (p = 1.0 in both cases). No differences were found between study arms after 6 and 24 h. CONCLUSIONS: The IM administration of 1% mepivacaine-diluted PGB induces significantly less immediate local pain as compared to PGB alone. The needle gauge did not have any effect on the pain. Based on these results, we suggest anesthetic-diluted IM PGB as the standard treatment for primary syphilis. TRIAL REGISTRATION: EudraCT 2014-003969-24 (Date of registration 18/09/2014).

Synthesis of a Crushed Fullerene C60H24 through Sixfold Palladium-Catalyzed Arylation.

The synthesis of a new C3v -symmetric crushed fullerene C60H24 (5) has been accomplished in three steps from truxene through sixfold palladium-catalyzed intramolecular arylation of a syn-trialkylated truxene precursor. Laser irradiation of 5 induces cyclodehydrogenation processes that result in the formation of C60, as detected by LDI-MS.

Clinical diagnostic accuracy of suspected sources of bacteremia and its effect on mortality.

BACKGROUND: Although much has been written about bacteremia, evidence of the clinical diagnostic accuracy of bacteremia sources in the absence of microbiological results and the impact of diagnostic accuracy on mortality is scarce. METHODS: This is a retrospective study of bacteremia episodes over a 2-year period at a general hospital in Madrid. Congruence analyses between clinically presumed and definite sources, acquisition, causative organism, empirical treatment and progression to death were performed. RESULTS: The study included 323 bacteremia episodes. Clinicians' diagnostic accuracy was higher for gastrointestinal (88.8%; 95% CI: 79%-84%), respiratory (93.9%; 95% CI: 79%-99%) and urinary tract sources (83.6%; 95% CI: 75%-89%) and lower for skin and soft tissues (77.2%; 95% CI: 54%-92%) and, notably, intravascular sources (56%; 95% CI: 39%-71%). Overall, a non-significant (3.45%; 95% CI: -0.6%-13.5%, p=0.47) increase in mortality was observed in the incorrectly suspected bacteremia source group. Mortality related to a definitive source was significantly higher when an intravascular origin was not suspected, resulting in a 26% increase in mortality (95% CI: 1%-52%, p=0.03). Differences in mortality related to inaccurate source assumptions were non-significant when the definitive bacteremia sources were gastrointestinal, urinary, respiratory, skin and soft tissues or unknown. Mortality in the group receiving appropriate empirical antimicrobial treatment was 10.6% compared with 19.7% mortality in the group receiving inappropriate empirical antimicrobial treatment (OR 2; 95% CI: 1.01-4.25). CONCLUSIONS: The diagnostic accuracy of bacteremia sources is high in all but intravascular sources. A non-suspected intravascular source and inappropriate empirical treatment are related to a higher mortality.

Imported malaria in pregnancy in Madrid.

BACKGROUND: Malaria in pregnancy is associated with maternal and foetal morbidity and mortality in endemic areas, but information on imported cases to non-endemic areas is scarce.The aim of this study was to describe the clinical and epidemiological characteristics of malaria in pregnancy in two general hospitals in Madrid, Spain. METHODS: Retrospective descriptive study of laboratory-confirmed malaria in pregnant women at the Fuenlabrada University Hospital and the Príncipe de Asturias University Hospital, in Madrid, over a six- and 11-year period, respectively. Relevant epidemiological, clinical and laboratory data was obtained from medical records. RESULTS: There were 19 pregnant women among 346 malaria cases (5.4%). The average age was 27 years. The gestational age (trimester) was: 53% 3rd, 31% 1st, 16% 2nd. All but one were multigravidae. Three were HIV positive. All were sub-Saharan immigrants: two were recently arrived immigrants and seventeen (89%) had visited friends and relatives. None had taken prophylaxis nor seeked pre-travel advice. PRESENTATION: 16 symptomatic patients (fever in fourteen, asthenia in two), three asymptomatic. Median delay in diagnosis: 7.5 days. Laboratory tests: anaemia (cut off Hb level 11 g/dl) 78.9% (mild 31.6%, moderate 31.6%, severe 15.8%) thrombocytopaenia 73.7%, hypoglycaemia 10.5%. All cases were due to Plasmodium falciparum, one case of hyperparasitaemia. Quinine + clindamycin prescribed in 84%. OUTCOMES: no severe maternal complications or deaths, two abortions, fifteen term pregnancies, no low-birth-weight newborns, two patients were lost to follow-up. CONCLUSIONS: Though cases of malaria in pregnancy are uncommon, a most at risk group is clearly defined: young sub-Saharan mothers visiting friends and relatives without pre-travel counselling and recently-arrived immigrants. The most common adverse maternal and foetal effects were anaemia and stillbirth. Given that presentation can be asymptomatic, malaria should always be considered in patients with unexplained anaemia arriving from endemic areas. These findings could help Maternal Health programme planners and implementers to target preventive interventions in the immigrant population and should create awareness among clinicians.

[Asymptomatic peripheral arterial disease detected by the ankle-brachial index in HIV-infected patients: prevalence and associated risk factors]. / Enfermedad arterial periférica asintomática estimada mediante el índice tobillo-brazo en pacientes con infección por el VIH: prevalencia y factores de riesgo asociados.

INTRODUCTION: Human immunodeficiency virus (HIV) infection has been associated with a higher risk of subclinical atherosclerosis and cardiovascular events. Peripheral arterial disease (PAD) is a good marker of systemic atherosclerosis and a powerful predictor of cardiovascular morbidity and mortality. The objective of this study was to determine the prevalence of asymptomatic PAD and associated risk factors in HIV-infected people. METHODS: Cross-sectional study was conducted on all consecutive HIV-positive patients older than 20 years without symptoms of intermittent claudication who attended our clinic between November 2008 and December 2009. PAD was assessed by measuring the ankle-brachial index (ABI) at rest. To define PAD, an ABI ≤ 0.90 was used. Main epidemiological and clinical characteristics of the HIV infection and cardiovascular risk factors (CVRF) were recorded. RESULTS: Two hundred and five patients were evaluated (66.8% male), with a mean age of 41 years and there was a median of 2 CVRF (63.9% smokers). Prevalence of asymptomatic PAD (ABI ≤ 0.90) was 6.3% (n=13). There was only 1 patient with a high ABI (>1.40). In the multivariate analysis, factors significantly associated with PAD were overweight (adjusted odds ratio [ORadj] 4.21; 95% confidence interval [CI] 1.00-18.78), obesity (ORadj 5.76; 95% CI 1.17-28.37) and clinical stage C of HIV infection (ORadj 2.95; 95% CI 1.00-9.83). CONCLUSIONS: Prevalence of asymptomatic PAD in a relatively young HIV-infected cohort is similar to that observed in the uninfected middle-aged adult population. Overweight, obesity and advanced clinical stage of HIV infection (AIDS-defining conditions) were identified as independent risk factors for PAD.

Enfermedad arterial periférica asintomática estimada mediante el índicetobillo-brazo en pacientes con infección por el VIH: prevalencia y factoresde riesgo asociados / Asymptomatic peripheral arterial disease detected by the ankle-brachial index in HIV-infected patients: prevalence and associated risk factors

Introducción: La infección por el virus de la inmunodeficiencia humana (VIH) se ha asociado a un mayor riesgo de aterosclerosis subclínica y de episodios cardiovasculares. La enfermedad arterial periférica (EAP)es un buen marcador de aterosclerosis sistémica y un importante predictor de morbilidad y mortalidad de origen cardiovascular. El objetivo de este estudio fue determinar la prevalencia de EAP asintomática y los factores de riesgo asociados en los pacientes infectados por el VIH. Métodos: Estudio transversal de los pacientes infectados por el VIH mayores de 20 años, sin síntomas de claudicación intermitente, atendidos de forma consecutiva en nuestra unidad entre noviembre de 2008 y diciembre de 2009. Se evaluó la presencia de EAP mediante la determinación del índice tobillo-brazo (ITB)en reposo. La EAP se definió como un ITB (..) (AU)

Introduction: Human immunodeficiency virus (HIV) infection has been associated with a higher risk of subclinical atherosclerosis and cardiovascular events. Peripheral arterial disease (PAD) is a good marker of systemic atherosclerosis and a powerful predictor of cardiovascular morbidity and mortality. The objective of this study was to determine the prevalence of asymptomatic PAD and associated risk factors in HIV-infected people. Methods: Cross-sectional study was conducted on all consecutive HIV-positive patients older than 20 years without symptoms of intermittent claudication who attended our clinic between November 2008 and December 2009. PAD was assessed by measuring the ankle-brachial index (ABI) at rest. To define PAD, an (..) (AU)

Herpes esophagitis in healthy adults and adolescents: report of 3 cases and review of the literature.

Herpes esophagitis (HE) is common in immunosuppressed patients, but has rarely been reported in immunocompetent individuals, in whom it appears to be a self-limited illness. We describe 3 new cases of HE in otherwise healthy patients seen in our hospital within the last 5 years. We performed a comprehensive review of the previously reported cases of HE in immunocompetent adults and adolescents in the English and Spanish literature. We analyzed the clinical features, treatment, and outcome of this entity. A total of 56 patients were included (39 men and 17 women), with a mean age of 35 years. The most common clinical manifestations were odynophagia (60.7%), fever (51.8%), and retrosternal chest pain (46.4%). A prodrome of upper respiratory symptoms and concurrent orolabial herpetic lesions were present in 26.8% and 25% of cases, respectively. Gastrointestinal bleeding was a rare complication (5.3%). Endoscopy revealed multiple ulcers in most cases (58.9%), typically involving the distal or mid-esophagus (83%). The diagnosis was confirmed by histopathologic examination in 40 cases (71.4%), by tissue viral culture in 21 (37.5%), and by detection of viral genome in esophageal samples in 4 cases (7.1%). Herpes simplex virus type 1 (HSV-1) was identified in 27 cases and herpes simplex virus type 2 (HSV-2) only in 1 case. Serology was consistent with a primary infection in 11 of the 25 evaluable cases (44%). Acyclovir therapy was used in 45.4% of patients. The outcome was favorable in all cases, although an esophageal perforation occurred in 1 patient. HE is a rare but well-defined entity in healthy adults and adolescents, and is probably underdiagnosed. A high degree of suspicion and a prompt endoscopic examination are required for the diagnosis. It is usually a self-limited infection, but early treatment with acyclovir may hasten the resolution of symptoms. Nevertheless, the benefit of antiviral therapy remains unknown.