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Infectious Diseases (London, England) Feb 2019Mycobacterium avium complex (MAC) infection is often disseminated and mainly involves lymph nodes, spleen, liver or bone marrow. Peritonitis due to MAC infection (PMAC)...
BACKGROUND
Mycobacterium avium complex (MAC) infection is often disseminated and mainly involves lymph nodes, spleen, liver or bone marrow. Peritonitis due to MAC infection (PMAC) is a very uncommon manifestation.
METHODS
In this report, after describing the case of the only PMAC infection in our 10-year retrospective study, which occurred in an AIDS patient who was non-adherent to highly active antiretroviral therapy (HAART), we performed a systematic literature review of documented bacteriological PMAC.
RESULTS
Including our patient, 51 cases of PMAC have been reported. Patients were most often male (sex ratio 2.14), with a median age of 41 years (2.8-72) and an immunodeficiency in all cases, most often AIDS (57%), cirrhosis (20%) and continuous ambulatory peritoneal dialysis (CAPD) (18%). Ascites was more often chylous (54%) than exudative (46%) and, in this case, lymphocytic (60%), with an inconstantly positive acid-fast bacilli smear (54%). Non-disseminated PMAC patients were more likely to have peritoneal dialysis (39% versus 6.5%, p < .01) or cancer with immunosuppressive therapy (39% versus 0%, p < .0001), while AIDS was the leading underlying disease in disseminated-PMAC patients (83% versus 11%, p < .001). Mortality was high (50%), with no difference between disseminated and non-disseminated PMAC.
CONCLUSIONS
This report highlights the need to be aware of an atypical presentation of PMAC infection, which is associated with a high rate of mortality even for non-disseminated infection.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Peritonitis; Retrospective Studies; Young Adult
PubMed: 30318980
DOI: 10.1080/23744235.2018.1519639 -
Cancer Treatment Reviews Sep 2017Anti-programmed death receptor 1 (PD-1) drugs nivolumab and pembrolizumab were recently approved for the treatment of advanced melanoma and other solid tumors. Atypical... (Comparative Study)
Comparative Study Review
Anti-programmed death receptor 1 (PD-1) drugs nivolumab and pembrolizumab were recently approved for the treatment of advanced melanoma and other solid tumors. Atypical patterns of response (i.e. tumor shrinkage or stabilization after initial progression) were observed in about 10% of metastatic melanoma patients treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) drug ipilimumab and were associated with improved survival; however, the rate of atypical response patterns to anti-PD-1 therapy is not clear. An electronic search was performed to identify clinical trials evaluating response to anti-PD-1 therapy with nivolumab and pembrolizumab in patients with advanced solid tumors. Thirty-eight studies were included in our analysis for a total of 7069 patients with advanced cancer treated with anti-PD-1 therapy. Responses were evaluated by unconventional response criteria in 19 trials and were observed for all cancer types but tumors with mismatch-repair deficiency and head and neck squamous cell carcinoma. Overall, 151 atypical responses were observed in 2400 patients (6%) evaluated by unconventional response criteria. The results of our systematic review highlight the clinical relevance of unconventional responses to anti-PD-1 therapy and support further investigation into the development of tools that may assist evaluation of the antitumor activity of immunotherapy.
Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Carcinoma, Renal Cell; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease-Free Survival; Female; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Melanoma; Middle Aged; Neoplasms; Nivolumab; Prognosis; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis
PubMed: 28756306
DOI: 10.1016/j.ctrv.2017.07.002 -
JAMA Apr 2016Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis. (Review)
Review
IMPORTANCE
Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis.
OBJECTIVE
To systematically review the literature regarding the value of the clinical examination and white blood cell count for the diagnosis of mononucleosis.
DATA SOURCES
The databases of PubMed (from 1966-2016) and EMBASE (from 1947-2015) were searched and a total of 670 articles and abstracts were reviewed for eligibility.
STUDY SELECTION
Eleven studies were included that reported data sufficient to calculate sensitivity, specificity, or both for clinical examination findings and white blood cell count parameters compared with a valid reference standard.
DATA EXTRACTION AND SYNTHESIS
Data were abstracted from each article by at least 2 reviewers, with discrepancies reconciled by consensus. Clinical findings evaluated in only 1 study are reported with sensitivity, specificity, likelihood ratio (LR), and 95% confidence interval, which were calculated from the available data. Findings evaluated in only 2 studies were summarized with their range, findings evaluated in 3 studies were summarized with a univariate random-effects summary, and findings evaluated in 4 or more studies were summarized with a bivariate random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES
Sensitivity, specificity, and LRs for the diagnosis of mononucleosis.
RESULTS
Mononucleosis is most commonly present among patients aged 5 to 25 years (especially those aged 16-20 years, among whom approximately 1 in 13 patients presenting with sore throat has mononucleosis). The likelihood of mononucleosis is reduced with the absence of any lymphadenopathy (summary sensitivity, 0.91; positive LR range, 0.23-0.44), whereas the likelihood increases with the presence of posterior cervical adenopathy (summary specificity, 0.87; positive LR, 3.1 [95% CI, 1.6-5.9]), inguinal or axillary adenopathy (specificity range, 0.82-0.91; positive LR range, 3.0-3.1), palatine petechiae (specificity, 0.95; positive LR, 5.3 [95% CI, 2.1-13]), and splenomegaly (specificity range, 0.71-0.99; positive LR range, 1.9-6.6). Symptoms are of limited value for the diagnosis of mononucleosis; sore throat and fatigue are sensitive (range, 0.81-0.83) but nonspecific. The presence of atypical lymphocytosis significantly increases the likelihood of mononucleosis (summary LR, 11.4 [95% CI, 2.7-35] for atypical lymphocytes ≥10%, 26 [95% CI, 9.6-68] for those with 20%, and 50 [95% CI, 38-64] for those with 40%). The combination of a patient having greater than 50% lymphocytes and greater than 10% atypical lymphocytes also is useful (specificity, 0.99; positive LR, 54 [95% CI, 8.4-189]).
CONCLUSIONS AND RELEVANCE
In adolescent and adult patients presenting with sore throat, the presence of posterior cervical, inguinal or axillary adenopathy, palatine petechiae, splenomegaly, or atypical lymphocytosis is associated with an increased likelihood of mononucleosis.
Topics: Adolescent; Adult; Axilla; Fatigue; Humans; Infectious Mononucleosis; Leukocyte Count; Lymphatic Diseases; Lymphocyte Count; Neck; Pharyngitis; Physical Examination; Purpura; Sensitivity and Specificity; Splenomegaly; Symptom Assessment; Young Adult
PubMed: 27115266
DOI: 10.1001/jama.2016.2111 -
BMC Medicine Sep 2015Targeting CTLA-4 is a recent strategic approach in cancer control: blocking CTLA-4 enhances an antitumor immunity by promoting T-cell activation and cytotoxic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Targeting CTLA-4 is a recent strategic approach in cancer control: blocking CTLA-4 enhances an antitumor immunity by promoting T-cell activation and cytotoxic T-lymphocyte proliferation. This induction of a tolerance break against the tumor may be responsible for immune-related adverse events (irAEs). Our objective was to assess the incidence and nature of irAEs in oncologic patients receiving anti-CTLA-4 antibodies (ipilimumab and tremelimumab).
METHODS
A systematic search of literature up to February 2014 was performed in MEDLINE, EMBASE, and Cochrane databases to identify relevant articles. Paired reviewers independently selected articles for inclusion and extracted data. Pooled incidence was calculated using R(©), package meta.
RESULTS
Overall, 81 articles were included in the study, with a total of 1265 patients from 22 clinical trials included in the meta-analysis. Described irAEs consisted of skin lesions (rash, pruritus, and vitiligo), colitis, and less frequently hepatitis, hypophysitis, thyroiditis, and some rare events such as sarcoidosis, uveitis, Guillain-Barré syndrome, immune-mediated cytopenia and polymyalgia rheumatic/Horton. The overall incidence of all-grade irAEs was 72 % (95 % CI, 65-79 %). The overall incidence of high-grade irAEs was 24 % (95 % CI, 18-30 %). The risk of developing irAEs was dependent of dosage, with incidence of all-grade irAEs being evaluated to 61 % (95 % CI, 56-66 %) for ipilimumab 3 mg/kg and 79 % (95 % CI, 69-89 %) for ipilimumab 10 mg/kg. Death due to irAEs occurred in 0.86 % of patients. The median time of onset of irAEs was about 10 weeks (IQR, 6-12) after the onset of treatment, corresponding with the first three cycles but varied according to the organ system involved. Such immune activation could also be indicative for tumor-specific T-cell activation and irAE occurrence was associated with clinical response to CTLA-4 blocking in 60 % of patients.
CONCLUSION
The price of potential long-term survival to metastatic tumors is an atypical immune toxicity, reflecting the mechanism of action of anti-CTLA-4 antibodies. A better knowledge of these irAEs and its management in a multidisciplinary approach will help to reduce morbidity and therapy interruptions.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; CTLA-4 Antigen; Humans; Immunologic Factors; Immunotherapy; Ipilimumab; Neoplasms
PubMed: 26337719
DOI: 10.1186/s12916-015-0455-8