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BACKGROUND: Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. METHODS: We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). RESULTS: Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, -14%; 95% CI, -19% to -8%; P < .001; I2 = 0%; relative risk, 0.58; 95% CI, .37-.92, P = .02, I2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. CONCLUSIONS: Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.
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Osteomielite , Infecções Estafilocócicas , Adulto , Humanos , Rifampina/uso terapêutico , Staphylococcus aureus , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/complicações , Protocolos Clínicos , Osteomielite/tratamento farmacológico , Osteomielite/etiologiaRESUMO
Immune checkpoint inhibitors are a new class of anticancer drugs recently approved by the US Food and Drug Administration (FDA) for the treatment of various malignancies. Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein-1 (PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2). Pembrolizumab was first approved by the FDA in 2014 for the treatment of advanced melanoma and is currently approved for use in non-small cell lung cancer and several other neoplasms. Immune checkpoint inhibitors such as pembrolizumab have been reported to induce immune-mediated side effects, including type 1 diabetes mellitus in very rare cases (0.1% in clinical trials). Here, we report the case of a woman with no known history of diabetes who presented to our emergency department in a state of diabetic ketoacidosis within 3â¯weeks of receiving only a single dose of pembrolizumab therapy, and without any previous exposure to immunotherapy. This case of abrupt adult-onset type 1 diabetes mellitus is an example of the undesirable side effects that can emerge after only a brief exposure to an immune checkpoint inhibitor. Close monitoring of patients receiving immune checkpoint inhibitors is warranted for the early diagnosis and management of imminent and potentially life-threatening complications.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Diabetes Mellitus Tipo 1/induzido quimicamente , Cetoacidose Diabética/induzido quimicamente , Neoplasias Cardíacas/tratamento farmacológico , Hemangiossarcoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Quimioterapia Adjuvante , Serviço Hospitalar de Emergência , Feminino , Neoplasias Cardíacas/cirurgia , Hemangiossarcoma/cirurgia , Humanos , Pessoa de Meia-Idade , Terapia NeoadjuvanteRESUMO
Enduring shortages of infectious disease physicians across the United States continue despite efforts to mitigate the problem. The recent fellowship match results underscore the difficulty in rectifying that shortage. Our report sheds light on the current geographic distribution of US infectious disease physicians and highlights the challenges faced by rural communities.
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Background: There are conflicting reports of the interaction between COVID-19 and HIV infection among coinfected individuals, and there is a particular dearth of evidence among populations in the Middle East. Aim: To determine if living with HIV and use of antiretroviral therapy increases susceptibility to, and severity of, COVID-19. Methods: This cross-sectional study was based on telephone survey of COVID-19 symptoms duration and clinical course among 200 people living with HIV (PLWHs) and a review of medical records in Beirut, Lebanon, during Spring 2021. Data were collected from consenting patients using standardized forms. The laboratory and medical characteristics of PLWHs with and without COVID-19 were compared and the outcomes of COVID-19 were described. A binary logistic regression model for contracting COVID-19 was constructed based on clinically relevant covariates consistently associated with COVID-19. Significance level was set at 0.05 and statistical analysis was performed using SPSS version 27.0. The Lebanese American University Institutional Review Board approved the study protocol. Results: Fifty-two of 200 PLWHs contracted COVID-19 but only 4 progressed to severe COVID-19. No significant differences were found with respect to gender, time since HIV diagnosis, most recent CD4 count, viral load, substance use, comorbidities, or use of antiretroviral therapy. Older PLWHs were at lower risk of contracting COVID-19; COVID-19 infection was significantly associated with younger age. Conclusions: COVID-19 infection was associated with younger age among PLWHs in Lebanon, possibly due to behavioural and socioeconomic factors.
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COVID-19 , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Líbano/epidemiologia , Estudos Transversais , COVID-19/epidemiologia , Inquéritos e QuestionáriosRESUMO
Cutibacterium acnes isolation from spine tissue can be challenging because the organism can represent a contaminant. There is a paucity of data regarding the role of C. acnes in non-hardware-associated vertebral osteomyelitis (VO). Herein we evaluate the clinical and microbiological characteristics, treatment, and outcome of patients with C. acnes VO. Data were retrospectively collected from adults with a positive spine culture for C. acnes at Mayo Clinic, Rochester (MN), from 2011 to 2021. Patients with spinal hardware and polymicrobial infections were excluded. Of the subjects, 16 showed radiological and clinical findings of VO: 87.5â¯% were male, the average age was 58 years (±15â¯SD), and back pain was the predominant symptom. Of the lesions, 89.5â¯% involved the thoracic spine. Of the subjects, 69â¯% had experienced an antecedent event at the site of VO. In five subjects, C. acnes was isolated after 7â¯d of anaerobic culture incubation. Thirteen subjects were treated with parenteral ß-lactams, and three with oral antimicrobials, without any evidence of recurrence. Twenty-one subjects were not treated for VO, as C. acnes was considered a contaminant; at follow-up, none had evidence of progressive disease. C. acnes should be part of microbiological differential diagnosis in patients with suspected VO, especially in the context of a prior spinal procedure. Anaerobic spine cultures should undergo prolonged incubation to enable recovery of C. acnes. C. acnes VO may be managed with oral or parenteral antimicrobial therapy. Without clinical and radiological evidence of VO, a single positive culture of C. acnes from spine tissue frequently represents contaminants.
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BACKGROUND CONTEXT: Native vertebral osteomyelitis (NVO) is a severe infection with an increasing incidence globally. Although there is no widely agreed upon reference standard for diagnosis of the disease, imaging plays a crucial role. Magnetic resonance imaging (MRI) is currently the imaging modality of choice. In recent years, advances in imaging have allowed for a larger role for alternative imaging techniques in the setting of NVO. PURPOSE: Our aim was to evaluate the diagnostic accuracy of MRI, PET/CT, and nuclear imaging, namely 67Gallium and 99mTechnetium scintigraphy, in the diagnosis of pyogenic NVO. STUDY DESIGN/SETTING: We conducted a systematic review of five medical databases and included all studies from 1970 to September 2021 that compared imaging techniques and provided sufficient data for diagnostic test accuracy meta-analysis. METHODS: Abstract screening, full text review, and data extraction were done by a pair of independent reviewers. Nonnative and nonpyogenic patients were excluded. A bivariate random effect model was used for meta-analysis. RESULTS: Twenty studies were included in the meta-analysis, encompassing a total of 1,123 imaging studies. The meta-analysis sensitivity and specificity of MRI were 90% and 72% respectively; those of PET/CT were 93% and 80%; those of 67Ga were 95% and 88%; those of 99mTc were 86% and 39%; and the sensitivity and specificity of combined Ga and Tc were 91% and 92% respectively in the setting of suspected NVO. CONCLUSIONS: 67Ga has the highest sensitivity for NVO, and its specificity is augmented when combined with 99mTc. MRI and PET/CT are both highly sensitive modalities, although the specificity of PET/CT is slightly better. MRI remains an appropriate initial test depending on the availability of other modalities.
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Imageamento por Ressonância Magnética , Osteomielite , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Osteomielite/diagnóstico por imagem , Cintilografia , Sensibilidade e EspecificidadeRESUMO
The discovery of immune checkpoint inhibitors (ICIs) has revolutionized the care of cancer patients. However, the response to ICI therapy exhibits substantial interindividual variability. Efforts have been directed to identify biomarkers that predict the clinical response to ICIs. In recent years, the gut microbiome has emerged as a critical player that influences the efficacy of immunotherapy. An increasing number of studies have suggested that the baseline composition of a patient's gut microbiota and its dysbiosis are correlated with the outcome of cancer immunotherapy. This review tackles the rapidly growing body of evidence evaluating the relationship between the gut microbiome and the response to ICI therapy. Additionally, this review highlights the impact of antibiotic-induced dysbiosis on ICI efficacy and discusses the possible therapeutic interventions to optimize the gut microbiota composition to augment immunotherapy efficacy.
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Native vertebral osteomyelitis (NVO) is a potentially fatal infection which has seen a gradual increase in its incidence over the past decades. The infection is insidious, presenting with symptoms of back pain. Fever is present in about 60â¯% of patients. Prompt diagnosis of NVO is important to prevent the development of complications. Numerous laboratory and imaging tools can be deployed to accurately establish the diagnosis. Imaging techniques such as magnetic resonance, nuclear imaging, and computed tomography are essential in diagnosing NVO but can also be useful in image-guided biopsies. Laboratory tools include routine blood tests, inflammatory markers, and routine culture techniques of aspirated specimens. Recent advances in molecular techniques can assist in identifying offending pathogen(s). In this review, we detail the arsenal of techniques that can be utilized to reach a diagnosis of NVO.
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Recent data suggest that oral therapy can be effective for bone infections. We aim to assess the efficacy of an early switch to oral therapy ( < 2 weeks) compared to a non-early switch in bacterial native vertebral osteomyelitis. We conducted a cohort study at Mayo Clinic, Rochester (MN), between 2019-2021 combined with a systematic review, which queried multiple databases. Data were analyzed using a random-effects model. The cohort study included 139 patients: two received an early switch. Of 3708 citations, 13 studies were included in the final analysis. Meta-analysis demonstrated no difference in treatment failure (odds ratio⯠= â¯1.073, 95â¯% confidence interval 0.370-3.116), but many studies presented high risk of bias. Current evidence is insufficient to conclude the proportion of patients with failure or relapse is different in the two groups. High-quality studies are warranted before early switch can be routinely recommended.
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Background: Image-guided biopsies in patients with suspected native vertebral osteomyelitis (NVO) are recommended to establish the microbiological diagnosis and guide antibiotic therapy. Despite recent advances, the microbiological yield of this procedure remains between 48% and 52%. A better understanding of factors associated with this low yield may lead to improved microbiological diagnosis. Methods: We retrospectively identified patients with suspected NVO undergoing image-guided biopsies from January 2011 to June 2021 at our institution. Two hundred nine patients undergoing 248 percutaneous biopsies were included. Demographic data, biopsy and microbiologic techniques, clinical characteristics, and antibiotic use were collected. Multivariable logistic regression analysis was conducted to determine factors associated with microbiological yield. Results: A total of 110 of 209 (52.6%) initial image-guided biopsies revealed positive microbiological results. This number increased to 121 of 209 (57.9%) when repeat image-guided biopsies were included. In multivariable analysis, aspiration of fluid was associated with a 3-fold increased odds of yielding a positive result (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.39-7.04; P = .006), whereas prior antibiotic use was associated with a 3-fold decreased yield (OR, 0.32; 95% CI, .16-.65; P = .002). A univariate subgroup analysis revealed a significant association between the length of the antibiotic-free period and microbiological yield, with the lowest rates of pathogen detection at 0-3 days and higher rates as duration increased (P = .017). Conclusions: Prior antibiotic use in patients with suspected NVO was associated with a decrease in the microbiological yield of image-guided biopsies. An antibiotic-free period of at least 4 days is suggested to maximize yield. Successful fluid aspiration during the procedure also increases microbiological yield.
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The Food and Drug Administration (FDA) approved the first SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech) in December 2020. New adverse events have emerged since these vaccines have reached market. Although no clear association between messenger ribonucleic acid (mRNA) vaccines and autoimmunity has emerged, the significance of such an association warrants further exploration. After obtaining consent, a standardized survey on baseline characteristics and other relevant variables was conducted on unvaccinated individuals who were scheduled for vaccination and had not previously contracted COVID-19. Blood samples were collected from participants prior to the first dose, prior to the second dose, and 1 month after the second dose. All collected samples were tested for antinuclear antibody (ANA) titers using indirect immunofluorescence microscopy kits, and antiphospholipid (APS) immunoglobulin M (IgM) and immunoglobulin G (IgG) levels using an enzyme-linked immunoassay (ELISA) technique. ANA titers were positive for 9 participants out of 101 (8.9%) in the first pre-vaccination draw. For the second draw, the number of participants testing positive for ANA decreased to 5 (5%). For the last draw, 6 (5.9%) participants tested positive for ANA titers. One participant tested positive for APS IgM at the first pre-vaccination draw, 2 tested positive at the second draw, and 2 at the third draw. As for APS IgG titers, all participants tested negative in the three draws. McNemar's test for two dependent categorical outcomes was conducted on all variables and did not show a statistical significance. The McNemar test of these two composite variables (i.e., ANA/APS, first draw vs. ANA/APS, second and third draws) did not show statistical significance. The 2-sided exact significance of the McNemar test was 1.0. The Friedman test also showed no significance (p = 0.459). No association was found between BNT162b2 vaccine administration and changes in APS and ANA titers. The benefits of the BNT162b2 vaccine significantly outweigh any possible risk of autoimmune dysregulation considering the current evidence.
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COVID-19 , Vacinas , Humanos , Anticorpos Antifosfolipídeos , Anticorpos Antinucleares , Vacina BNT162 , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Imunoglobulina M , Imunoglobulina G , Anticorpos Antivirais , Vacinas de mRNARESUMO
Cancer patients have increased risk of infections, and often present to emergency departments with infection-related problems where physicians must make decisions based on a snapshot of the patient's condition. Although C-reactive protein, procalcitonin, and lactate are popular biomarkers of sepsis, their use in guiding emergency care of cancer patients with infections is unclear. Using these biomarkers, we created a prediction model for short-term mortality in cancer patients with suspected infection. We retrospectively analyzed all consecutive patients who visited the emergency department of MD Anderson Cancer Center between 1 April 2018 and 30 April 2019. A clinical decision model was developed using multiple logistic regression for various clinical and laboratory biomarkers; coefficients were used to generate a prediction score stratifying patients into four groups according to their 14-day mortality risk. The prediction score had an area under the receiver operating characteristic curve value of 0.88 (95% confidence interval 0.85-0.91) in predicting 14-day mortality. The prediction score also accurately predicted intensive care unit admission and 30-day mortality. Our simple new scoring system for mortality prediction, based on readily available clinical and laboratory data, including procalcitonin, C-reactive protein, and lactate, can be used in emergency departments for cancer patients with suspected infection.
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Immunotherapy with checkpoint inhibitors has revolutionized cancer therapy and is now the standard treatment for several different types of cancer, supported by favorable outcomes and good tolerance. However, it is linked to multiple immune manifestations, referred to as immune-related adverse events (irAEs). These adverse events frequently affect the skin, colon, endocrine glands, lungs, and liver. The gastrointestinal system is one of the most commonly affected organ systems and is responsible for the most frequent emergency visits resulting from irAEs. However, because immune checkpoint inhibitors are a recent addition to our arsenal of cancer drugs, many health-care providers remain unfamiliar with the management of irAEs. Gastroenterologists involved in the treatment of oncology patients who have received checkpoint inhibitors are currently encountering cases of abdominal pain, diarrhea, and other nonspecific symptoms that may be challenging to manage. This article reviews the gastrointestinal, hepatic, and pancreatic toxicities of checkpoint inhibitors and provides an approach to their diagnosis and recommended workup. It also highlights the management of irAEs according to their toxicity grading and specifically discusses the instances in which corticosteroids should be administered and/or the immune checkpoint inhibitors should be withheld.