Bisphosphonate-associated osteonecrosis of the jaw 2 years after teeth extractions: a case report solved with non-invasive treatment.

Bisphosphonates are a type of drugs known to inhibit bone resorption through complex interventions. Their primary mechanism of action is aimed at the cellular level, inhibiting osteoclast activity and, thus, bone resorption. Bisphosphonates are, therefore, very widely used, with many patients receiving continuous treatment for years. But it is well known that these drugs can produce osteonecrosis of the jaw and this is their principal risk. A 75-year-old woman received dental treatment before starting intravenous BP therapy for a breast cancer. She started intravenous bisphosphonate treatment with monthly protocol and after two years the patient presented a wound compatible with osteonecrosis of the jaw.

Efecto hemodinámico de la ivabradina en 3 pacientes críticos con estenosis aórtica severa / Hemodynamic effect of ivabradine in three critical patients with severe aortic stenosis

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Risk factors and clinical significance of invasive infections caused by levofloxacin-resistant Streptococcus pneumoniae.

PURPOSE: Fluoroquinolones are recommended for the treatment of pneumonia. The recognition of risk factors for invasive levofloxacin-resistant Streptococcus pneumoniae is important for the design of treatment. METHODS: A retrospective review of cases of invasive pneumococcal infections in adults was undertaken. Epidemiologic data, predisposing factors, clinical variables, and outcome were recorded from previously established protocols. Antimicrobial susceptibility was determined by disk diffusion and the Etest method. Serotyping was performed by latex agglutination and Quellung reaction. RESULTS: Twenty patients with infection caused by levofloxacin-resistant pneumococci [minimum inhibitory concentration (MIC) ≥2 µg/ml] were compared with 102 patients harboring levofloxacin-susceptible strains; 80% of levofloxacin-resistant pneumococci were resistant to ≥3 antibiotics but susceptible to penicillin. Most levofloxacin-resistant strains (80%) belonged to serotype 8. In comparison, only 8% of levofloxacin-susceptible pneumococci belonged to serotype 8. In the multivariate analysis, residence in public shelters [odds ratio (OR) 26.13; p 0.002], previous hospitalization (OR 61.77; p < 0.001), human immunodeficiency virus (HIV) infection (OR 28.14; p = 0.009), and heavy smoking (OR 14.41; p = 0.016) were associated with an increased risk of infection by levofloxacin-resistant pneumococci. Mortality caused by levofloxacin-resistant and levofloxacin-susceptible pneumococci was 35 and 14%, respectively. Among HIV-positive individuals infected with levofloxacin-resistant pneumococci 44% died, but only 12.5% of HIV-positive patients with levofloxacin-susceptible strains died. CONCLUSIONS: We observed the emergence of serotype 8 as the main cause of invasive disease caused by levofloxacin-resistant S. pneumoniae. HIV-positive patients seem to be prone to infection caused by multidrug-resistant serotype 8 and have a high mortality rate.

Antimicrobial treatment of invasive non-perinatal human listeriosis and the impact of the underlying disease on prognosis.

Listeriosis is a resurgent foodborne disease in European countries. Benefits of combined ß-lactam-aminoglycoside treatment remain controversial and the impact of the underlying disease on prognosis has not been fully assessed. We conducted a retrospective review of cases of sporadic listeriosis in adults from 1995 to 2008 at two university-affiliated hospitals serving a population of 600,000 people in Madrid, Spain. The primary end-point was the associated in-hospital mortality. Sixty-four patients were studied. Estimated incidence of listeriosis was 0.76/100.000 persons/year. Seventy-four per cent had chronic underlying diseases; cirrhosis of the liver and haematological and solid neoplasias were the most common comorbidities. Primary bacteraemia (58%) and meningitis (42%) were the most frequent manifestations. Focal infections were seen in ten cases. In-hospital mortality was 31%. Patients treated with ampicillin or with an ampicillin-gentamicin combination did not differ in age, severity of underlying disease or type of presentation. Differences in mortality were not seen between patients treated with monotherapy and those given combined treatment (28% vs 35%; p 0.634). Ten patients were treated with trimethoprim-sulfamethozaxole alone and only one died. All patients without comorbidities survived infection but mortality of patients with cirrhosis of the liver was 21% and that of patients with haematological or solid neoplasias was 66%. Only haematological neoplasia (OR 6.67; 95% CI 1.71-26.04; p 0.006) was significantly associated with an increased risk of mortality (R(2) (Cox-Snell) = 0.262). Mortality of listeriosis mainly depended on the severity of the underlying disease. Combined ampicillin-gentamicin therapy did not improved survival. Trimethoprim-sulfamethozaxole may be an effective alternative therapy for listerial infections.

Emerging infectious endocarditis due to Scedosporium prolificans: a model of therapeutic complexity.

Scedosporium prolificans is an emerging agent for severe infections. Although among the dematiaceous fungi Scedosporium is the most frequently isolated in blood cultures, Scedosporium endocarditis is rarely reported. We show herein a patient with acute leukaemia who developed S. prolificans endocarditis. Twelve cases were found in an extensive review of the English literature. In six cases (46%), there was predisposing heart conditions such as a prosthetic valve or an intracavitary device. Only 4 patients (31%) were immunocompromised hosts with haematologic neoplasia, solid-organ transplantation or acquired immunodeficiency syndrome (AIDS). Exposure to Scedosporium was observed in immunocompetent patients who developed infection while in the community. Scedosporium endocarditis occurred on both sides of the heart. Systemic and pulmonary emboli and other metastatic complications were seen in all of these patients. The overall mortality was 77% and, specifically, all of the immunocompromised hosts and 6 out of 7 patients with mitral or aortic valve endocarditis died. Patients with right-sided endocarditis associated with a removable intracardiac device exhibited a better prognosis. Scedosporium endocarditis, although still rare, is an emerging infection with an ominous prognosis. At the present time, valve replacement or the removal of cardiac devices plus combined antifungal treatment may offer the best possibility of cure.

Infectious endocarditis in patients with cirrhosis of the liver: a model of infection in the frail patient.

The purposes of this paper was to discover whether cirrhosis is a predisposing cause of infectious endocarditis (IE) and to determine the microbiology, prognosis and the role of cardiac surgery on mortality. A review of cases of IE at a university-affiliated hospital over a period of 10 years was conducted. Thirty-one (9.8%) patients among 316 cases of IE had hepatic cirrhosis. Valve disorders were present in 62.2% of cirrhotic patients and infection occurred on the aortic (48%) and mitral valves (45%). Endocarditis was hospital-acquired in 14 (45%) and 11 (17.7%) cirrhotic patients and controls, respectively (odds ratio [OR] 3.82; 95% confidence interval [CI]: 1.46-9.99; p = 0.005). Staphylococcus aureus was the most common causative microorganism, but ß-hemolytic streptococci were most frequently isolated in cirrhotic patients (OR 8.75; 95% CI: 1.7-45.2; p = 0.001). Renal failure was more frequent in patients with cirrhosis (OR 8.23; 95% CI: 3.06-22.2; p = 0.001). Cirrhotic patients had a higher mortality (51% vs. 17.7%; OR 4.95; 95% CI: 1.89-12.91; p = 0.001) associated with the severity of liver disease. Valve replacement was performed less frequently in cirrhotic patients (56.2% vs. 92%) and the operative mortality was extremely high in patients at stages B and C. Hepatic cirrhosis is a frequent comorbid condition in patients with endocarditis. Due to the presence of severe hepatic dysfunction, cardiac surgery is not undertaken even when indicated and mortality is high in stages B and C. Endocarditis is a serious hazard for hospitalized cirrhotic patients.

Nephrotic syndrome complicating chronic visceral leishmaniasis: re-emergence in patients with AIDS.

Leishmania infection may be associated with immunecomplex-mediated glomerular injury. Contrary to immune-competent individuals, leishmaniasis in HIV patients is a chronic, relapsing disease. Despite the increasing frequency of the Leishmania/ HIV co-infection, there is a paucity of information on the effects of such co-infection in the kidney. We present a patient with AIDS and refractory, relapsing visceral leishmaniasis who developed nephrotic syndrome associated with renal involvement by Leishmania in the absence of immunecomplex glomerular deposition. For the first time, the relapsing nature of renal injury in this context is documented.

Patients' perception and effectiveness of a treatment containing enfuvirtide when used in HIV-infected patients without very advanced disease.

PURPOSE: To evaluate the satisfaction with self-injected enfuvirtide (ENF) and the clinical outcome of HIV-infected patients without very advanced disease. METHOD: ESPPE is a multicenter observational study that included 103 evaluated patients showing baseline characteristics predictive of positive outcome: CD4 >100 cells/mm3, viral load (VL) <100,000 copies/mL, previous treatment with a maximum of 10 antiretroviral drugs, and concomitant use of 2 active drugs. By using validated surveys, patients were questioned 6 months after the prescription of ENF about their quality of life (QoL) and acceptance of self-injections and adherence to the treatment. RESULTS: At 6 months, the mean CD4 increase was 121 cells/mm3 (p < .05) and 65% (intent-to-treat, ENF stopped=failure) had VL <50 copies/mL (p < .001). Fourteen patients discontinued the treatment, mostly due to intolerance (6). The majority (>89%) assessed all items relating QoL as "excellent," "very good," or "good." The treatment satisfaction index on a visual analog scale scored a median of 8.1 out of 10; when participants were asked about the interference of injections on their daily activities, 87% answered "never" or "only sometimes." CONCLUSION: Effectiveness and patients' perception about ENF remain good when ENF was used in patients without very advanced disease. QoL was not impaired after ENF use.

Evolution of bone mineral density in AIDS patients on treatment with zidovudine/lamivudine plus abacavir or lopinavir/ritonavir.

OBJECTIVES: The aim of the study was to determine the factors that may contribute to decreases in bone mineral density (BMD) in patients with AIDS. METHODS: This was a prospective, non-randomized study. Dual X-ray absorptiometry (DXA) was used to determine the BMD of the lumbar spine, femoral neck and distal radius in treatment-naïve HIV-infected male patients with AIDS before and after 1 year of treatment with zidovudine (ZDV)/lamivudine (3TC) plus abacavir (ABC) or lopinavir/ritonavir (LPV/r). RESULTS: Basal DXA was performed in 50 patients with CD4 counts <200 cells/microL and/or any AIDS-defining condition. Thirty-two patients completed 1 year with full adherence (17 on ABC and 15 on LPV/r) and a second DXA was then performed. At baseline, 19% had osteopenia at the lumbar spine and 19% at the femoral neck. Low body weight was related to low BMD. After 48 weeks, BMD loss was significant at the three locations. The percentage of BMD loss at the femoral neck tended to be greater in the lopinavir group (5.3 vs. 3.2%, P=0.058). The differences became significant at the lumbar spine (5.7 vs. 2.7%, P=0.044). In the multivariate analysis, the treatment with LPV/r remained associated with bone loss at the lumbar spine. CONCLUSIONS: Osteopenia is frequent in treatment-naïve HIV-infected men with AIDS. Bone loss is higher with LPV/r-based regimens compared with triple nucleoside reverse transcriptase inhibitors.

The role of splenectomy in HIV-infected patients with relapsing visceral leishmaniasis.

The treatment of visceral leishmaniasis (VL) in HIV-infected patients is characterized by having a protracted course and frequent relapses, despite the use of adequate anti-leishmanial drugs and effective anti-retroviral therapy. A small subset of patients with significant splenomegaly develops severe cytopaenias and chronic leishmania infection. The use of elective splenectomy is effective for restoring the haematological parameters and reduces the need for blood transfusions but it does not avoid relapsing visceral leishmaniasis.

Tratamiento farmacológico de los trastoros de personalidad / Drug treatment with personality disorders

Revisamos la concepción mayoritaria de que los trastornos de la personalidad (TP) no son susceptibles de tratamiento farmacológico por tratarse de alteraciones que están relacionadas con la estructura de la personalidad y sus aspectos puramente psíquicos, haciendo posteriormente un repaso a las propuestas más generalizadas y contrastadas empíricamente acerca de las posibilidades terapéuticas de los psicofármacos en estos trastornos. Aunque la utilización de la terapia biológica se va convirtiendo en una práctica habitual, no existe ningún medicamento aprobado oficialmente para este tipo de afecciones. Con estos presupuestos, hacemos un breve repaso a las presuntas bases bioquímicas de los TP y sus dimensiones clínicas (esfera cognitiva, afectiva e impulsiva) para, a partir de ahí, hacer propuestas farmacológicas concretas, ordenadas en forma de algoritmo. Finalizamos esta exposición señalando el "conflicto de intereses" que se plantea entre lo conocido y lo que no sabemos aún sobre la fisiopatología de los trastornos mentales en general y de la personalidad en particular. Presentamos como riesgo el hecho de que las hipótesis bioquímicas consigan enraizarse como verdades absolutas, estimulando investigaciones alentadas (y financiadas) por las compañías farmacéuticas. Proponemos, finalmente, el cambio a un modelo centrado en el paciente, donde la descripción que éste hace de los efectos del fármaco sea el puntal esencial de intervención (AU)

This paper examines the prevaling opinión that personality disorders are resistant to drug treatment since they refer to personality structure and are purely psychological. Then, a review of the most relevant empirically-based theories about the therapeutic power of drug treatments in this respect is made. Although drug treatment is becoming a frequent treatment, no drug has yet been officially determined for this kind of disorders. Besed on the above statements, a brief review of biochemical bases of personality disorders and their clinical dimensions (cognitive, affective and behavioural signs), a number of suggestions for drug treatment are made in the form of an algorithm. There is a conflict of interests between what is known and what is unknown about physiopathology of mental disorders, particularly personality. There is the risk that biochemical hypothesis become absolute truths and the overlook corporative interests behin them. Finally, a suggestion is also made for a shift to a patient-centeres approach that highlights patient perceived effects of the drug should be taken into account at the time to intervene (AU)

Infections of implantable cardioverter-defibrillators: frequency, predisposing factors and clinical significance.

The prognosis for patients with ventricular arrhythmias has improved dramatically with the aid of implantable cardioverter-defibrillators (ICDs). Although infection is a serious complication that frequently causes dysfunction and loss of ICDs, the frequency, predisposing risk-factors, and clinical and microbiological features are only partially understood. This study describes a retrospective review of 423 procedures in 278 patients with ICD primary implants and replacements performed at a tertiary-care hospital. Generators were placed in either a pectoral (68%) or abdominal (32%) site, and electrodes were placed transvenously in 97% of the patients. Most (95%) interventions were performed in a one-stage procedure. Infection developed with ten (2.4%) implanted devices. Four cases occurred within 30 days of surgery ('early infections') and six occurred > 1 month after surgery ('late infections'). In univariate analysis, factors associated with the development of an early infection were: two-stage surgery, a sub-costal approach, and abdominal generator placement. In patients with late infections, a significant association was found with trauma or decubitus ulcer in the generator area. Infection presented with local signs without systemic complications. Seven of the ten patients required complete removal of the system.

Enfermedad de Castleman multicéntrica en sida. Su relación con el VHH-8 o virus herpes asociadoal sarcoma de Kaposi. Estudio de dos casos / Multicenter Castleman disease in AIDS. Its relationship with HHV-8 or hespes virus associated to Kaposi's sarcoma. Study of two cases

La enfermedad de Castleman está considerada como un cuadro linfadenopático reactivo con dos formas clínicas: una localizada, frecuente en pacientes inmunocompetentes, y otra multicéntrica, más característica en los enfermos inmunodeprimidos. Se presentan dos casos de enfermedad de Castleman multicéntrica en pacientes VIH positivos con sarcoma de Kaposi. Ambos pacientes muestran adenopatías múltiples, hepatomegalia y síntomas B al diagnóstico. Uno de ellos presenta respuesta favorable al tratamiento quimioterápico y el otro fallece. Se realiza una revisión del concepto de enfermedad de Castleman multicéntrica, así como su relación patogénica con el virus herpes humano-8

Castleman disease is considered a reactive lymphadenopathic picture with two clinical forms: one localized, frequent in immunocompetent patients and another multicenter one that is more characteristic in immunodepressed patients. Two cases of Castleman disease multicenter in HIV positive patients with Kaposi's sarcoma are presented. Both patients have multiple adenopathies, hepatomegaly and symptoms B on diagnosis. One of them had a favorable response to chemotherapy treatment and another died. A review of the concept of multicenter Castleman disease and its pathogenic relationship to human herpes virus 8 (HHV-8) is done

Pleuropulmonary infections caused by Mycobacterium bovis: a re-emerging disease.

Between 1980 and 2003, 13 patients (0.95% of all cases of tuberculosis) at a 600-bed university hospital in Madrid, Spain, were diagnosed with Mycobacterium bovis infection. All 13 cases occurred between 1994 and 1999; the mean age of the patients was 50 years (range 23-83 years), and 77% were males. Four (30%) patients were also positive for human immunodeficiency virus (HIV). The most frequent localisation of the disease was the lung (ten patients; 77%). Seven patients, including four HIV-positive patients who died, had multidrug-resistant M. bovis infection. No other patient died, including two HIV-negative patients with multidrug-resistant disease.

A randomized controlled trial investigating the efficacy and safety of switching from a protease inhibitor to nevirapine in patients with undetectable viral load.

OBJECTIVE: To assess the antiviral efficacy and safety of switching from a protease inhibitor (PI) to nevirapine in patients with long-term HIV-1 RNA suppression on PI-containing regimens, and to assess its influence in the adherence to treatment. METHODS: In an open-label multicentre study, 160 HIV-infected patients with undetectable viral load for at least 6 months on a PI-containing regimen were randomized to either continue with their PI regimen (n=79) or replace PI with nevirapine (n=81). Clinical assessment included plasma HIV-1 RNA, blood chemistry, haematology, lymphocyte counts and adverse events reports. Adherence to treatment and lipodystrophy syndrome were assessed by patient self-reporting. RESULTS: Treatment efficacy was equivalent in the two arms, for patients with viral loads either above or below 100 000 HIV-1 RNA copies/mL. The increase in CD4 cell count was significant in both arms (P<0.00001) but the average CD4 cell count at 48 weeks was slightly higher in the nevirapine arm (596 vs. 569; P=0.1588). The number of patients with severe hypertriglyceridaemia (>400 mg/dL) after 48 weeks of treatment decreased in the nevirapine arm (from 11 to six), but increased in the PI arm (from four to 11) and led to treatment discontinuation in two patients. Lipodystrophy changes increased in 15% of patients in the PI arm but decreased in 4% of patients in the nevirapine arm. Finally, although adherence was similar in the two arms, patients reported that it required significantly less effort to stay on treatment in the nevirapine arm. Conclusions The results indicate that switching from PI to nevirapine is as effective as continuing with PI for maintaining viral control, even in patients with baseline viral load above 100,000 copies/mL. In addition, reductions in hypertriglyceridaemia and lipodystrophy and in the effort required to stay on treatment were observed.

[Central nervous system infections in HIV patients in the era of high activity antiretroviral treatment]. / Las infecciones del sistema nervioso central en pacientes con virus de la inmunodeficiencia humana en la era del tratamiento antirretroviral de gran actividad.

Although the incidence of most central nervous system infections in HIV+ patients has decreased after the introduction of the modern antiretroviral treatments, they are still a major cause of morbidity and mortality. New technologies in molecular biology and neuroradiology establish the diagnosis in many cases and have decreased the need for cerebral biopsy. Prognosis has improved substantially after the introduction of high activity antiretroviral treatment; more active treatments are needed, however, for infections as PML or citomegalovirus encephalitis because of their still unacceptably high mortality.

Las infecciones del sistema nervioso central en pacientes con virus de la inmunodeficiencia humana en la era del tratamiento antirretroviral de gran actividad / Central nervous system infections in HIV patients in the era of high activity antiretroviral treatment

Aunque la incidencia de la mayoría de las infecciones del sistema nervioso central en los pacientes infectados por el virus de la inmunodeficiencia humana ha disminuido tras la introducción de los modernos tratamientos antirretrovirales, aún siguen siendo una causa importante de morbilidad y mortalidad. Las nuevas tecnologías en biología molecular y neurorradiología permiten el diagnóstico en muchos casos y han disminuido la necesidad de la biopsia cerebral. El pronóstico ha mejorado sustancialmente tras la introducción de la terapia antirretroviral de alta eficacia, pero, sin embargo, se precisan tratamientos más activos para infecciones como la LMP o la encefalitis por citomegalovirus donde la mortalidad sigue siendo inaceptablemente alta

Although the incidence of most central nervous system infections in HIV+ patients has decreased after the introduction of the modern antiretroviral treatments, they are still a major cause of morbidity and mortality. New technologies in molecular biology and neuroradiology establish the diagnosis in many cases and have decreased the need for cerebral biopsy. Prognosis has improved substantially after the introduction of high activity antiretroviral treatment; more active treatments are needed, however, for infections as PML or citomegalovirus encephalitis because of their still unacceptably high mortality