RESUMO
The xenotropic murine leukemia virus-related virus (XMRV) has been recently linked to chronic fatigue syndrome in a US cohort in whom the virus was demonstrated in 67% patients vs 3.7% healthy controls. Albeit this finding was not substantiated by subsequent reports and eventually considered a laboratory contamination, the matter is still the object of intense debate and scrutiny in various cohorts of patients. In this work we examined well-clinically characterized Italian patients affected by chronic fatigue syndrome, and also fibromyalgia and rheumatoid arthritis, two chronic illnesses of basically unknown etiology which show quite a few symptoms in common with chronic fatigue syndrome. Although we used recently updated procedures and controls, the XMRV was not found in 65 patients with chronic fatigue syndrome diagnosis, 55 with fibromyalgia, 25 with rheumatoid arthritis, nor in 25 healthy controls. These results add to the ever-growing number of surveys reporting the absence of XMRV in chronic fatigue syndrome patients and suggest that the virus is also absent in fibromyalgia and rheumatoid arthritis.
Assuntos
Artrite Reumatoide/virologia , Síndrome de Fadiga Crônica/virologia , Fibromialgia/virologia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/isolamento & purificação , Adulto , Artrite Reumatoide/epidemiologia , Estudos de Casos e Controles , Síndrome de Fadiga Crônica/epidemiologia , Feminino , Fibromialgia/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de RiscoRESUMO
The aim of this review was to describe the recent literature concerning sexual dysfunction in fibromyalgic patients. To this end, we used the common online databases PubMed, MEDLINE and EMBASE (up to June 2012) and searched for the key words fibromyalgia (FM) and sexual dysfunction. All the studies examined underlined that FM is strictly associated with sexual dysfunction in women. The major findings observed were related to a decreased sexual desire and arousal, decreased experience of orgasm, and in some studies an increase in genital pain. The psychological aspects, together with the stress related to the constant presence of chronic widespread pain, fatigue and sleep disturbances, are certainly a major factor that adversely affects the sexuality of the patient with FM. Moreover, the drugs most commonly used in these cases may interfere negatively on the sexuality and sexual function of these patients. Therefore, the therapeutic intervention should be targeted and the side effects should be weighed up against the positive effects. It is of the utmost importance to recognise the problem of sexuality and sexual dysfunction in a more complex form of its expression and undertake a multidisciplinary therapeutic intervention to improve the quality of FM patients' life.
Assuntos
Fibromialgia/complicações , Qualidade de Vida , Disfunções Sexuais Psicogênicas/etiologia , Dor Crônica/etiologia , Medicina Baseada em Evidências , Fadiga/etiologia , Feminino , Fibromialgia/diagnóstico , Fibromialgia/psicologia , Fibromialgia/terapia , Humanos , Comunicação Interdisciplinar , Privação do Sono/etiologiaRESUMO
The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients. Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs. The primary outcome was the time to nasopharyngeal swab negativization. A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization. Of 280 patients included, 59 (21.1%) patients were treated with steroids. Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO2/FiO2 ≤ 200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p = 0.023) or ≤ 100 mmHg (16.9% vs 12.7%; p = 0.027), and length of hospitalization (20 vs 14 days; p < 0.001). Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p = 0.985). According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤ 70 years, a shorter duration of symptoms at admission, a baseline PaO2/FiO2 > 200 mmHg, and a lymphocyte count at admission > 1.0 × 109/L. SARS-CoV-2 clearance was not associated with corticosteroid use. Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with an early use of corticosteroids.
Assuntos
Corticosteroides/uso terapêutico , Tratamento Farmacológico da COVID-19 , Carga Viral/efeitos dos fármacos , Fatores Etários , Idoso , COVID-19/epidemiologia , Feminino , Hospitalização , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infections are an emerging cause of death after hematopoietic stem cell transplantation (HSCT). In allogeneic transplants, mortality rate may rise up to 60%. We retrospectively evaluated 540 patients receiving a transplant from an auto- or an allogeneic source between January 2011 and October 2015. After an Institutional increase in the prevalence of KPC-Kp bloodstream infections (BSI) in June 2012, from July 2012, 366 consecutive patients received the following preventive measures: (i) weekly rectal swabs for surveillance; (ii) contact precautions in carriers (iii) early-targeted therapy in neutropenic febrile carriers. Molecular typing identified KPC-Kp clone ST512 as the main clone responsible for colonization, BSI and outbreaks. After the introduction of these preventive measures, the cumulative incidence of KPC-Kp BSI (P=0.01) and septic shocks (P=0.01) at 1 year after HSCT was significantly reduced. KPC-Kp infection-mortality dropped from 62.5% (pre-intervention) to 16.6% (post-intervention). Day 100 transplant-related mortality and KPC-Kp infection-related mortality after allogeneic HSCT were reduced from 22% to 10% (P=0.001) and from 4% to 1% (P=0.04), respectively. None of the pre-HSCT carriers was excluded from transplant. These results suggest that active surveillance, contact precautions and early-targeted therapies, may efficiently control KPC-Kp spread and related mortality even after allogeneic HSCT.
Assuntos
Proteínas de Bactérias/biossíntese , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Infecções por Klebsiella , Klebsiella pneumoniae , Choque Séptico , beta-Lactamases/biossíntese , Adolescente , Adulto , Idoso , Aloenxertos , Autoenxertos , Feminino , Seguimentos , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Infecções por Klebsiella/genética , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/terapia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/patogenicidade , Masculino , Pessoa de Meia-Idade , Choque Séptico/genética , Choque Séptico/mortalidade , Choque Séptico/terapiaRESUMO
Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by unexplained fatigue not improved by rest. An area of investigation is the likely connection of CFS with defective mitochondrial function. In a previous work, we investigated the proteomic salivary profile in a couple of monozygotic twins discordant for CFS. Following this work, we analyzed mitochondrial proteins in the same couple of twins. Nano-liquid chromatography electrospray ionization mass spectrometry (nano-LC-MS) was used to study the mitochondria extracted from platelets of the twins. Subsequently, we selected three proteins that were validated using western blot analysis in a big cohort of subjects (n=45 CFS; n=45 healthy), using whole saliva (WS). The selected proteins were as follows: aconitate hydratase (ACON), ATP synthase subunit beta (ATPB) and malate dehydrogenase (MDHM). Results for ATPB and ACON confirmed their upregulation in CFS. However, the MDHM alteration was not confirmed. Thereafter, seeing the great variability of clinical features of CFS patients, we decided to analyze the expression of our proteins after splitting patients according to clinical parameters. For each marker, the values were actually higher in the group of patients who had clinical features similar to the ill twin. In conclusion, these results suggest that our potential markers could be one of the criteria to be taken into account for helping in diagnosis. Furthermore, the identification of biomarkers present in particular subgroups of CFS patients may help in shedding light upon the complex entity of CFS. Moreover, it could help in developing tailored treatments.
RESUMO
OBJECTIVE: To investigate the usefulness of polymerase chain reaction (PCR) from cerebrospinal fluid (CSF) for rapid diagnosis and assessing treatment response of tuberculous meningitis (TBM) in AIDS patients. PATIENTS: Forty-four CSF samples from 10 patients with TBM confirmed by autopsy or by a culture of CSF (41 samples) and from two patients with highly probable TBM (three samples) were analysed. CSF specimens were collected before and during standard antituberculous treatment. CSF samples from 24 AIDS patients with autopsy evidence of other neurologic diseases were studied as controls. METHODS: A nested PCR amplifying a 123 base-pair fragment of the IS6110 sequence was developed. Heating to 95 degrees C for 15 min was used for pre-PCR treatment of samples. RESULTS: Detection limit was 10(2) colony-forming units per ml or 10 fg purified Mycobacterium tuberculosis DNA. M.tuberculosis DNA was detected in CSF from all the 12 confirmed or highly probable TBM cases. CSF was positive by nested PCR in 17 of 17 (100%) and 18 of 27 (67%) samples collected before and during therapy, respectively. Clinical and microbiological follow-up > or = 2 weeks was available for seven patients. PCR-positive CSF converted to M. tuberculosis DNA negative in four patients that showed improvement during treatment, but it remained positive in three patients who died of disseminated tuberculosis. All the CSF samples from the non-TBM controls were negative by nested PCR. CONCLUSIONS: Nested PCR for detection of M. tuberculosis DNA is specific for diagnosis of TBM and more sensitive than conventional bacteriology. Moreover, nested PCR could be a useful method for assessing treatment response in AIDS patients with TBM.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Reação em Cadeia da Polimerase/métodos , Tuberculose Meníngea/complicações , Tuberculose Meníngea/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Sequência de Bases , Primers do DNA/genética , DNA Bacteriano/líquido cefalorraquidiano , DNA Bacteriano/genética , Estudos de Avaliação como Assunto , Humanos , Dados de Sequência Molecular , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase/estatística & dados numéricos , Sensibilidade e Especificidade , Tuberculose Meníngea/microbiologiaRESUMO
Anti-CD4 antibodies have been documented in about 10-20% of HIV-infected patients. This autoimmune response could be triggered by increased CD4 processing and unveiling of hidden (cryptic) epitopes. Multiple markers of exposure to HIV have been described in exposed uninfected individuals. Here, we investigated the mechanisms underlying the generation of anti-CD4 antibodies in a cohort of 54 seronegative exposed uninfected individuals. We identified anti-CD4 antibodies above normal levels in 16 of 47 (34%) exposed uninfected subjects. The fine specificity of these antibodies was different in this cohort when compared with those found in HIV+ patients. This suggested the possibility of different mechanisms underlying the generation of anti-CD4 antibodies in these two groups. Indeed, in exposed uninfected subjects, we found circulating CD4 T cells specific for gp120, but not for CD4. In contrast, HIV-1-seropositive patients had peripheral blood T cells specific for both molecules. Noncovalent binding of gp120 to soluble CD4 enhanced activation of gp120-specific T lymphocytes in exposed uninfected subjects, but not in HIV+ subjects. Moreover, gp120-specific T cells isolated from exposed uninfected, but not from HIV+, subjects provided help for anti-CD4 antibody production by B cells pulsed with CD4-gp120 complex. We conclude that gp120-specific T cells are present in exposed uninfected individuals, and can provide intermolecular help for anti-CD4 antibody production. This mechanism is distinct from that found in HIV-1-seropositive patients and may play a protective role against HIV-1 infection in vivo.
Assuntos
Autoanticorpos/biossíntese , Antígenos CD4/imunologia , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Linfócitos T/imunologia , Células Clonais/imunologia , Soropositividade para HIV/imunologia , Humanos , Imunoglobulina G/imunologiaRESUMO
We evaluated the sensitivity and specificity of a nested polymerase chain reaction (PCR) to the Mycobacterium tuberculosis IS6110 sequence on formalin-fixed paraffin-embedded tissue samples from patients with tubercular and other granulomatous lesions. Five groups of patients and samples were studied: (1) 28 samples from HIV-positive patients with tuberculosis, (2) 8 samples from HIV-negative patients with histologically suspected tuberculosis (confirmed by culture in 5 cases), (3) lymph nodes from 5 HIV-positive patients with Mycobacterium avium-intracellulare infection, (4) lymph nodes from 30 patients with sarcoidosis, and (5) specimens from 17 patients with other granulomatous diseases. The DNA was extracted from sections with a total thickness of 60 microm, and PCR amplified an internal fragment of 123 base pairs. All of the cases with M. tuberculosis infection were PCR-positive, although this sensitivity was partially related to the initial concentration of the DNA used for amplification. Two of the group 4 samples also were repeatedly positive, thus reducing the specificity of the method. All of the cases with granulomatous diseases other than sarcoidosis were negative. We propose a simplified and highly sensitive nested PCR for the diagnosis of M. tuberculosis infection on archived material in HIV-positive and HIV-negative patients.
Assuntos
Granuloma/complicações , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Síndrome da Imunodeficiência Adquirida/complicações , Biópsia , Estudos de Avaliação como Assunto , Feminino , Formaldeído , Humanos , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Inclusão em Parafina , Reação em Cadeia da Polimerase , Sarcoidose/complicações , Sensibilidade e Especificidade , Tuberculose/complicaçõesRESUMO
Isoniazid (INH) resistance was genotypically assessed in 104 (37 INH-susceptible, 67 INH-resistant) genetically unrelated Mycobacterium tuberculosis strains cultured in North Italy. The PCR products of selected regions of the katG gene, the oxyR-ahpC intergenic region, and the inhA regulatory region were analyzed utilizing the double gradient-denaturing gradient gel electrophoresis (DG-DGGE) technique and confirmed by DNA sequencing. Mutations were detected in 61 (91%) of the INH-resistant strains, the relative frequency of the mutations being 65.7% in katG, 23.9% in oxyR-ahpC, and 13.4% in inhA. Previously described alterations, invariably associated with drug resistance, accounted for 95.1% of the mutations. No alterations were found in the INH-susceptible strains. DG-DGGE analysis and DNA sequencing were equally sensitive, but the former is cheaper, easier and more robust. Rapid genotypic assessment of INH resistance by means of the methodology described here could reasonably be used in clinical mycobacteriology laboratories.
Assuntos
Antituberculosos/farmacologia , Proteínas de Bactérias , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Análise Mutacional de DNA , DNA Bacteriano/análise , Farmacorresistência Bacteriana , Eletroforese/métodos , Genótipo , Humanos , Peroxidases/genética , Sensibilidade e EspecificidadeRESUMO
Diagnosis of invasive fungal infection remains challenging. Here we report a case of early diagnosis of invasive aspergillosis in a neutropenic patient affected by acute myeloid leukaemia, achieved through the detection of Aspergillus fumigatus species-specific ribonucleic acid sequences by a sensitive multiplex real-time polymerase chain reaction-based molecular assay. Thanks to the early diagnosis, targeted therapy was promptly established and the severe fungal infection controlled, allowing the patient to subsequently receive allogeneic hematopoietic stem cell transplantation from a haploidentical donor, her only curative option. Also in this instance, targeted secondary antifungal prophylaxis with voriconazole avoided any other fungal infection afterwards. This report suggests how the implementation of molecular assays in combination with routine diagnostic procedures, can improve microbiological diagnosis in sepsis, particularly in case of fungal infection, difficult to detect with standard microbiological culture methods.
Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/classificação , Acinetobacter baumannii/enzimologia , Idoso , Infecção Hospitalar/tratamento farmacológico , Surtos de Doenças , Farmacorresistência Bacteriana , Genótipo , Humanos , Unidades de Terapia Intensiva , Itália/epidemiologia , Masculino , Isolamento de Pacientes , Transferência de Pacientes , beta-LactamasesAssuntos
Transplante de Células-Tronco Hematopoéticas , Sirolimo/administração & dosagem , Condicionamento Pré-Transplante , Triazóis/administração & dosagem , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Doença de Hodgkin/terapia , Humanos , Leucemia Mieloide Aguda/terapia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Indução de Remissão , Risco , Transplante Homólogo , Resultado do Tratamento , Adulto JovemAssuntos
Ampicilina/análogos & derivados , Fezes/microbiologia , Administração Oral , Adulto , Ampicilina/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Feminino , Humanos , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella oxytoca/isolamento & purificação , Masculino , Valores de ReferênciaAssuntos
Fezes/microbiologia , Ofloxacino/farmacologia , Adulto , Antibacterianos/farmacologia , Bactérias Aeróbias/efeitos dos fármacos , Bactérias Aeróbias/isolamento & purificação , Bactérias Anaeróbias/efeitos dos fármacos , Bactérias Anaeróbias/isolamento & purificação , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Valores de ReferênciaRESUMO
The aims of the study were to analyze the clinical and epidemiological characteristics and treatments for patients who developed zygomycosis enrolled in Italy during the European Confederation of Medical Mycology of medical mycology survey. This prospective multicenter study was performed between 2004 and 2007 at 49 italian Departments. 60 cases of zygomycosis were enrolled: the median age was 59.5 years (range 1-87), with a prevalence of males (70%). The majority of cases were immunocompromised patients (42 cases, 70%), mainly hematological malignancies (37). Among non-immunocompromised (18 cases, 30%), the main category was represented by patients with penetrating trauma (7/18, 39%). The most common sites of infection were sinus (35%) with/without CNS involvement, lung alone (25%), skin (20%), but in 11 cases (18%) dissemination was observed. According to EORTC criteria, the diagnosis of zygomycosis was proven in 46 patients (77%) and in most of them it was made in vivo (40/46 patients, 87%); in the remaining 14 cases (23%) the diagnosis was probable. 51 patients received antifungal therapy and in 30 of them surgical debridement was also performed. The most commonly used antifungal drug was liposomal amphotericin B (L-AmB), administered in 44 patients: 36 of these patients (82%) responded to therapy. Altogether an attributable mortality rate of 32% (19/60) was registered, which was reduced to 18% in patients treated with L-AmB (8/44). Zygomycosis is a rare and aggressive filamentous fungal infection, still associated with a high mortality rate. This study indicates an inversion of this trend, with a better prognosis and significantly lower mortality than that reported in the literature. It is possible that new extensive, aggressive diagnostic and therapeutic procedures, such as the use of L-AmB and surgery, have improved the prognosis of these patients.
Assuntos
Zigomicose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Farmacorresistência Fúngica , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Zigomicose/diagnóstico , Zigomicose/tratamento farmacológico , Zigomicose/etiologiaRESUMO
A total of 108 volunteers undergoing an elective surgical procedure were randomly given a single 2-g intravenous prophylactic dose of either a cephalosporin or mezlocillin. Stool samples were cultured for Clostridium difficile the day before the operation and later on postoperative days 4, 7, and 14. C. difficile was detected in 23.0% of patients who received a cephalosporin (cefoxitin, 8.3%; cefazolin, 14.3%; cefotetan, 20.0%; ceftriaxone, 25.0%; cefoperazone, 43.7%), in 3.3% of patients given mezlocillin, and in none of 15 control volunteers given no antimicrobial agent. No patient experienced diarrhea.
Assuntos
Antibacterianos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Intestinos/microbiologia , Pré-Medicação , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Enterocolite Pseudomembranosa/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Indomethacin 50 mg i.v. or p.o. and diclofenac sodium 50 mg p.o. produced a prompt and significant increase in plasma free fatty acid concentration. In 10 subjects who took indomethacin 150 mg/d p.o. for 3 days, plasma post-heparin lipoprotein lipase activity was also significantly increased. The same effect occurred in 9 subjects treated for 3 days with diclofenac sodium 50 mg t.d.s. Since both indomethacin and diclofenac sodium are potent inhibitors of prostaglandin synthetase, these findings are consistent with the hypothesis tht prostaglandins are involved in the feed-back regulation of lipolysis, and mediate the inhibitory effect of lipolysis on lipoprotein lipase activity.
Assuntos
Diclofenaco/farmacologia , Heparina/farmacologia , Indometacina/farmacologia , Lipólise/efeitos dos fármacos , Lipase Lipoproteica/sangue , Fenilacetatos/farmacologia , Adulto , Idoso , Glicemia/análise , Colesterol/sangue , Inibidores de Ciclo-Oxigenase , Ácidos Graxos não Esterificados/sangue , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
The main clinical features of patients who developed pseudomembranous colitis (PMC) or Clostridium difficile-associated diarrhoea (CDAD) during their stay at the S. Anna General Hospital, Como, over the period February 1984 to May 1988, are reported. Forty patients developed either CDAD (ten cases) or PMC (30 cases). Twenty-seven (65.7%) had undergone surgery and 32 (80.0%) had received prolonged antibiotic treatment. Three patients (7.5%) were given three doses only of ceftriaxone. Five patients (12.5%) had not received any antibiotic treatment; but three were nursed in a bed next to a patient with PMC-CDAD. The number of cases diagnosed were correlated retrospectively with the cumulative consumption of different groups of antibiotics on wards in which PMC or CDAD occurred. A significant difference (P less than 0.01) between third generation cephalosporins (16 cases) and ureidopenicillins (one case), was found. Twenty-five patients were treated with oral vancomycin. Two died of the underlying disease and 23 were cured. The disease recurred clinically in three, and follow-up cultures were positive in another asymptomatic case. Fifteen patients (all PMC cases) were treated with oral teicoplanin. All were clinically cured and remained asymptomatic and all but one were also cleared of C. difficile. No adverse reactions were observed in patients given either drug. Third generation cephalosporins, even when administered as short-term perioperative prophylaxis, but not ureidopenicillins, are significantly associated with C. difficile-related diseases. Teicoplanin proved to be very effective and safe in the treatment of PMC, and should be further evaluated there.