Immunosuppressed patients with pandemic influenza A 2009 (H1N1) virus infection.

The purpose of this paper was to prospectively characterize the clinical manifestations and outcomes of confirmed influenza A 2009 (H1N1) virus infection in immunosuppressed patients with hospital admission and compare them with those of a general population. A multicenter prospective cohort study was carried out. All adult patients admitted to 13 hospitals in Spain with confirmed influenza A 2009 (H1N1) virus infection from June 12, 2009 to November 11, 2009 were included. Risk factors for complicated influenza infection were studied in immunosuppressed patients. Overall, 559 patients were included, of which 56 were immunosuppressed, nine with solid or hematological malignancies, 18 with solid-organ transplant recipients, 13 with corticosteroid therapy, and six with other types of immunosuppression. Clinical findings at diagnosis were similar in both groups. Nineteen immunosuppressed patients had pneumonia (33.9%). Immunosuppressed patients with pandemic influenza had bacterial co-infection more frequently (17.9% vs. 6.4%, p = 0.02), specifically, gram-negative bacilli and Staphylococcus aureus infections. Mortality was higher in immunosuppressed patients (7.1% vs. 1.8%, p < 0.05). The only modifiable risk factor of complicated influenza A 2009 (H1N1) was delayed antiviral therapy. In immunosuppressed patients, influenza A 2009 (H1N1) virus infection has higher mortality than in non-immunosuppressed individuals. Bacterial co-infection is common in complicated cases.

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir/Abacavir/Lamivudine in Antiretroviral-Naive Adults (SYMTRI): A Multicenter Randomized Open-Label Study (PReEC/RIS-57).

BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. METHODS: Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B∗5701 negative and hepatitis B virus negative), with viral load (VL) ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the intention-to-treat (ITT)-exposed population (US Food and Drug Administration snapshot analysis, 10% noninferiority margin). RESULTS: Between September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. Forty percent had a baseline VL >100 000 copies/mL, and 13% had <200 CD4 cells/µL. Median weight was 73 kg and median body mass index was 24 kg/m2. At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes. CONCLUSIONS: We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated.

Incidental Skin Cancer Detection in a Hospital Department: A Prospective Study. / Evaluación de la tasa de detección incidental de cáncer cutáneo: estudio prospectivo en un servicio hospitalario.

BACKGROUND AND OBJECTIVES: Skin cancer is a common cause for referral to dermatology, but it may also be an incidental finding during examination of patients referred for other reasons. The objective of the study was to compare the characteristics of skin cancer lesions (squamous skin carcinoma, basal cell carcinoma, melanoma) diagnosed at a dermatology department over 1 year between patients referred for suspected skin cancer and those referred for another reason but in whom skin cancer was detected as an incidental finding. Pearson's χ2 test was used to compare different study variables between the 2 groups. RESULTS: Data were collected from 433 patients with a mean age of 72 years; 233 (51.3%) of the patients were female. The most common skin types were Fitzpatrick types II and III. Basal cell carcinoma was the most frequent cancer in all the analyses and accounted for 68.4% of all cancers diagnosed (296/433). Twenty-six percent of the malignant skin tumors were detected incidentally. Statistical analysis revealed that these tumors tended to be located in nonvisible areas and were smaller and of more recent onset than tumors initially suspected to be malignant. CONCLUSIONS: The high rate of skin cancer diagnosed incidentally by dermatologists highlights the need to carry out thorough examinations of patients in order to facilitate early detection and treatment.

A new bronchoscopic technique for the diagnosis of bacterial pneumonia in HIV-positive patients.

The aim of the present study was to evaluate in HIV-positive patients with bacterial pneumonia, the diagnostic value of a new endoscopic technique that uses a single catheter to perform a telescopic plugged catheter (TPC) followed by a modified protected bronchoalveolar lavage (mpBAL). Fifty-eight HIV-positive patients with respiratory infection were included in the study. Samples from TPC and mpBAL were cultured quantitatively. Standard bronchoalveolar lavage was performed to rule out opportunistic infections. According to the clinical and microbiological results, patients were classified in the study group (27 with bacterial pneumonia) or the control group (31 without bacterial pneumonia). Sensitivity of TPC was 56% [95% confidence intervals (CI) 37-75%] and its specificity was 100%; these figures were 56% (CI, 37-75%) and 94% (CI, 86-100%) for mpBAL. When both techniques were assessed together, sensitivity increased to 70% (CI, 53-87%). The use of a single catheter reduced the cost of the originally described pBAL procedure by approximately 50%. The use of a single catheter to perform a TPC followed by a mpBAL can improve the diagnostic yield in HIV-positive patients with bacterial pneumonia, and reduces its cost.

Radiologic features of Rhodococcus equi pneumonia in AIDS.

This report outlines the radiological features observed in three cases of Rhodococcus equi (R. equi) pneumonia in AIDS (acquired immunodeficiency syndrome) and reviews another 45 radiological reports published of this emerging opportunistic pneumonia in Human Immunodeficiency Virus (HIV) infected patients. The clinical signs in our three patients consisted in a subacute onset of respiratory symptoms and fever. A low lymphocyte count (< 200 cells/mm3), pulmonary infiltrates, and pleural effusion was present in all three cases. Cavitary pneumonia was observed in two patients, and pericardial effusion in another. In this series CD4 lymphocyte count < 200/mm3 was seen in 29 of the 48 patients (60.4%). All 48 patients had abnormal findings on chest radiographs. Abnormalities involved the upper lobes in 26 of the 48 patients (55%). Cavitation was reported in 37 of the 48 cases (77%). R. equi pneumonia may not be as the paucity of case reports suggest. Consequently, a cavitary pneumonia in HIV infected patients with a low CD4 lymphocyte count (< 200 mm3) with a subacute onset, an upper lobe predilection, and/or a poor response to conventional antibiotic therapy should be considered as suspect of R. equi infection.

Indinavir crystallization and urolithiasis.

The crystallization of indinavir in synthetic urine at different pH values and indinavir concentrations was kinetically studied. It was found that precipitation time notably decreases at urinary pH values above 6.0. The effects of some products as potential crystallization inhibitors were studied. Some natural saponins such as escin and glycyrrhizic acid provoked a notable increase in the precipitation time of indinavir, this pointing out their possible use to prevent renal tubular solid deposition.

Changes in epidemiology, clinical features and severity of influenza A (H1N1) 2009 pneumonia in the first post-pandemic influenza season.

Although the influenza A (H1N1) 2009 virus is expected to circulate as a seasonal virus for some years after the pandemic period, its behaviour cannot be predicted. We analysed a prospective cohort study of hospitalized adults with influenza A (H1N1) 2009 pneumonia at 14 teaching hospitals in Spain to compare the epidemiology, clinical features and outcomes of influenza A (H1N1) 2009 pneumonia between the pandemic period and the first post-pandemic influenza season. A total of 348 patients were included: 234 during the pandemic period and 114 during the first post-pandemic influenza season. Patients during the post-pandemic period were older and more likely to have chronic obstructive pulmonary disease, chronic kidney disease and cancer than the others. Septic shock, altered mental status and respiratory failure on arrival at hospital were significantly more common during the post-pandemic period. Time from illness onset to receipt of antiviral therapy was also longer during this period. Early antiviral therapy was less frequently administered to patients during the post-pandemic period (22.9% versus 10.9%; p 0.009). In addition, length of stay was longer, and need for mechanical ventilation and intensive-care unit admission were significantly higher during the post-pandemic period. In-hospital mortality (5.1% versus 21.2%; p <0.001) was also greater during this period. In conclusion, significant epidemiological changes and an increased severity of influenza A (H1N1) 2009 pneumonia were found in the first post-pandemic influenza season. Physicians should consider influenza A (H1N1) 2009 when selecting microbiological testing and treatment in patients with pneumonia in the upcoming influenza season.

Mannose-binding lectin does not act as an acute-phase reactant in adults with community-acquired pneumococcal pneumonia.

The objective of this work was to study the role of mannose-binding lectin (MBL) and C-reactive protein (CRP) in pneumococcal pneumonia, to determine whether MBL acts as an acute-phase reactant and whether the severity of the disease correlates with MBL levels. The study comprised 100 patients with pneumococcal pneumonia. The pneumonia severity score was calculated and graded into a risk class of mortality (Fine scale). The MBL genotypes and the levels of MBL and CRP at the acute and recovery phases were determined. Fifty patients with the wild-type MBL genotype showed higher MBL levels in each phase (P < 0.001) and an increased risk to developing bacteraemia, odds ratio (OR) 2.74, 95% confidence interval (CI) 1.01-7.52) (P = 0.02), but this did not correlate with the pneumonia severity class. CRP levels in the acute phase, 79.53 mg/l [standard deviation (s.d.) 106.93], were higher in the subjects with positive blood cultures (P = 0.003), and remained higher [20.12 mg/l (s.d. 31.90)] in the group of patients with an underlying disease (P = 0.01). No correlation was observed between the levels of MBL and CRP in each phase, or with the pneumonia severity score. We cannot conclude that MBL acts uniformly as an acute-phase reactant in pneumococcal pneumonia. MBL levels do not correlate well with the severity of the pneumonia. The risk of developing bacteraemia could be enhanced in individuals with the wild-type MBL genotype.

[Utility of extended release indapamide in the treatment of hypertension in at risk elderly: extended release study]. / Utilidad de indapamida retard en el tratamiento de la hipertensión arterial en población anciana de riesgo. Estudio RETARD.

INTRODUCTION: It is estimated that more than 65% of the elderly population in Spain is hypertensive. This study aimed to evaluate the safety and efficacy of extended release indapamide in hypertensive patients over 60 years of age, having high cardiovascular risk and the factors that influence this effect. MATERIAL AND METHODS: Prospective study made in 944 patients with essential HBP and age > 60 years (55.9% women) in whom treatment with extended release indapamide in single drug therapy or in combination was indicated, whether as a new drug or due to lack of efficacy of the previous therapy. The action scope was hospital out-patient clinics of Internal Medicine and follow-up time of the patients was 6 months. RESULTS: Extended release indapamide causes a significant decrease (p < 0.05) of systolic blood pressure (SBP) (21.3 mmHg) and diastolic blood pressure (DBP) (10.8 mmHg). No significant differences were found between the results in monotherapy or combined therapy. A total of 52.7% of the patients included had 3 or more cardiovascular risk factors (RF) or had target organ lesion (TOL) and 41.1% had an associated cardiovascular disease (CVD). Those patients with greater baseline SBP and DBP were those having a greater decrease in BP. On the other hand, patients with 1 or 2 RF showed a greater decrease of the SBP in comparison with patients with 3 or more RF, TOL or associated CVD. The adverse reactions rate was 2.8%. CONCLUSIONS: Extended release indapamide is an effective drug in the elderly population having high cardiovascular risk and is well tolerated.

Risk factors in HIV-1-infected patients developing repetitive bacterial infections: toxicological, clinical, specific antibody class responses, opsonophagocytosis and Fc(gamma) RIIa polymorphism characteristics.

The aim of the study was to determine possible factors related to the risk of developing recurrent bacterial respiratory tract infections in HIV-1-infected patients, regardless of the degree of immune cellular impairment. Thirty-three HIV-1 seropositive patients with previous repetitive bacterial respiratory tract infections (case group), 33 HIV-1 seropositive controls (matched by CD4-cell counts) without these antecedents and 27 healthy controls were studied before and after administration of pneumococcal and Haemophilus influenzae type b vaccines. Clinical or toxicological variables, cutaneous tests, complement factors, beta2-microglobulin, serum IgM, IgA, IgG and subclasses, specific antibodies (IgG, IgG2, IgA) against pneumococcal vaccine and polyribosylribitol phosphate (PRP), their avidity, opsonophagocytosis and IgG(2)m and Fc(gamma)RIIa allotypes were determined. A history of drug abuse (P = 0.001), less likelihood of receiving high activity antiretroviral treatment high activity antiretroviral treatment (HAART) (P = 0.01), higher levels of HIV-1 viral load (P < 0.05), serum IgG (P < 0.01) and beta2-microglobulin (P < 0.01) were observed in the case group. Also, a lower increase in specific antibodies to pneumococcal vaccine and PRP was demonstrated in the cases in comparison with the two control groups. No differences were observed in the avidity of antibodies, opsonophagocytic capacity or IgG(2)m and Fc(gamma)RIIa allotypes between the three groups. These data indicate that vaccination strategies against encapsulated bacteria can be unsuccessful in the HIV-1-infected patients presenting repetitive bacterial respiratory tract infections if behavioural aspects or measures to improve adherence to HAART therapies are not considered.

Obstruction and normal recanalization of the ureter in the human embryo. Its relation to congenital ureteric obstruction.

In this work, after the study of 45 normal human embryos of 5-55 mm from vertex to coccyx, it is shown that the ureteric ducts, which in the first phases of development are permeable (embryos of 5-13 mm), constantly undergo a process of obstruction and posterior recanalization of their lumen, which takes place when they are from 14 to 22 mm. These processes begin in the middle zone of the ureters and progress proximally and distally until they cover its entire length, for which these ducts, which in embryos of approximately 17 mm in length form solid cords, but in the embryos of 23 mm are totally permeable. This obstructive process is found in relation to atrophy and loss of activity of the mesonephros, while that of recanalization follows the intense longitudinal growth of the ureters in this phase of development. These modifications, which the ureteric lumen normally undergoes during its embryonic development, are of great importance for correct interpretation of the pathogenic mechanism of congenital ureteric strictures and valves.

[Obstruction and normal rechannelization of the ureter in the human embryo. Relations to stenoses and congenital ureteral valves]. / Obstruction et recanalisation normales de l'uretère chez l'embryon humain. Relations avec les sténoses et les valvules uretérales congénitales.

Study of 5 normal human embryos from 5 to 55 mm in length from vertex to coccyx, shows that the ureteric ducts, which in the first phases of development are permeable (embryos of 5-13 mm, Streeter's Horizons XIII-XVII, age from 28 +/- 1 to 35 +/- 1 days), constantly undergo a process of obstruction and a subsequent recanalization of their lumen, which takes place when the embryos measure from 14 to 22 mm. The processes begin in the middle zone of the ureters and progress proximally and distally until they cover its entire length. These ducts, which in embryos of approximately 17 mm in length form solid cords, are totally permeable in embryos of 23 mm. These modifications are of great importance for correct interpretation of the pathogenic mechanism of congenital ureteric strictures and valves.

[Pseudomonas spp. infections in patients with HIV infections]. / Infecciones por Pseudomonas spp. en pacientes con infección por HIV.

BACKGROUND: The aim of this study was to describe the characteristics of the infections by Pseudomonas spp. observed in patients with HIV infection in Spain. METHODS: A retrospective study was performed of the isolations of Pseudomonas spp. in microbiologic samples of patients with HIV infection in three hospitals from Mallorca, Spain, since 1986. RESULTS: Twenty-nine patients with some positive culture for Pseudomonas were reviewed. In 20 cases the infection presented in advanced stages of the disease when the patient fulfilled AIDS criteria. The most frequent foci in both community acquired and nosocomial infection was respiratory (16 and 3 cases, respectively). Fifty percent of the cases presented bacteremia. The classically described predisposing factors for infection by this germ were presented in 19 patients. Pseudomonas aeruginosa was the most frequently isolated type (22 cases). Only 5 patients received the appropriate treatment on admission. Clinical cure was achieved in 23 patients, with recurrence being observed in 10. Five patients died in relation to the infection. CONCLUSIONS: Infections by Pseudomonas spp. in Spain appear to have increased in frequency in patients with HIV infection in the last decade. These infections appear in advanced phases of the disease and mainly involve the lung, with high rates of bacteremia and a high number of recurrence. Empiric treatment of patients with advanced HIV infection with suspicion of bacterial infection should include antipseudomonic drugs.

Efficient and selective aerobic oxidation of alcohols into aldehydes and ketones using ruthenium/TEMPO as the catalytic system.

The combination of RuCl2(PPh3)3 and TEMPO affords an efficient catalytic system for the aerobic oxidation of a variety of primary and secondary alcohols, giving the corresponding aldehydes and ketones, in >99% selectivity in all cases. The Ru/TEMPO system displayed a preference for primary vs secondary alcohols. Results from Hammett correlation studies (rho = -0.58) and the primary kinetic isotope effect (kH/kD = 5.1) for the catalytic aerobic benzyl alcohol oxidations are inconsistent with either an oxoruthenium (O=Ru) or an oxoammonium based mechanism. We postulate a hydridometal mechanism, involving a "RuH2(PPh3)3" species as the active catalyst. TEMPO acts as a hydrogen transfer mediator and is either regenerated by oxygen, under catalytic aerobic conditions, or converted to TEMPH under stoichiometric anaerobic conditions.