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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 -
Frontiers in Immunology 2021Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations...
Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations due to unknown mechanisms. The demographic, clinical, immunological and genetic data were collected by direct interview and examining the Iranian AT patients with late-onset manifestations. We also conducted a systematic literature review for reported atypical AT patients. We identified three Iranian AT patients (3/249, 1.2% of total registry) with later age at ataxia onset and slower neurologic progression despite elevated alpha-fetoprotein levels, history of respiratory infections, and immunological features of the syndrome. Of note, all patients developed autoimmunity in which a decrease of naïve T cells and regulatory T cells were observed. The literature searches also summarized data from 73 variant AT patients with atypical presentation indicating biallelic mild mutations mainly lead to an atypical phenotype with an increased risk of cancer. Variant AT patients present with milder phenotype or atypical form of classical symptoms causing under- or mis- diagnosis. Although missense mutations are more frequent, an atypical presentation can be associated with deleterious mutations due to unknown modifying factors.
Topics: Adolescent; Adult; Ataxia; Ataxia Telangiectasia; Child; Child, Preschool; Female; Humans; Iran; Male; Mutation, Missense; Phenotype; T-Lymphocytes, Regulatory; Young Adult; alpha-Fetoproteins
PubMed: 35095854
DOI: 10.3389/fimmu.2021.779502 -
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 -
Biochemistry Research International 2021This study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in... (Review)
Review
BACKGROUND
This study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in children to provide a reference for clinical practice.
METHODS
We employed a literature search of databases such as PubMed, Web of Science, EMBASE, and Johns Hopkins University for articles on COVID-19-related multisystem inflammatory syndrome in children published between April 1, 2020, and January 15, 2021. High-quality articles were selected for analysis on the basis of their quality standard scores. Using R3.6.3 software, meta-analyses of random- or fixed-effects models were used to determine the prevalence of comorbidities. Subgroup analysis was also performed to determine heterogeneity.
RESULTS
A total of 57 articles (2,290 pediatric patients) were included in the study. . :ncidences of fever, gastrointestinal symptoms, respiratory symptoms, and musculoskeletal symptoms (myalgias or arthralgias) were 99.91% (95% CI: 99.67-100%), 82.72% (95% CI: 78.19-86.81%), 53.02% (45.28-60.68%), and 14.16% (95% CI: 8.4-21.12%), respectively. The incidences of rash, conjunctival injection, lymphadenopathy, dry cracked lips, neurologic symptoms (headache, altered mental status, or confusion), swollen hands and feet, typical Kawasaki disease, and atypical Kawasaki disease were 59.34% (95% CI: 54.73-63.87%), 55.23% (95% CI: 50.22-60.19%), 27.07% (95% CI: 19.87-34.93%), 46.37% (95% CI: 39.97-52.83%), 28.87% (95% CI: 22.76-35.40%), 28.75% (95% CI: 21.46-36.64%), 17.32% (95% CI: 15.44-19.29%), and 36.19% (95% CI: 21.90-51.86%), respectively. The incidences of coronary artery dilation, aneurysm, pericardial effusion, myocarditis, myocardial dysfunction, high troponin, and -terminal pro-B-type natriuretic peptide were 17.83%, 6.85%, 20.97%, 35.97%, 56.32%, 76.34%, and 86.65%, respectively. The incidences of reduced lymphocytes, thrombocytopenia, hypoalbuminemia, elevated C-reactive protein, ferritin, LDH, interleukin-6, PCT, and FIB were 61.51%, 26.42%, 77.92%, 98.5%, 86.79%, 80.59%, 89.30%, 85.10%, and 87.01%, respectively. . The incidences of PICU hospitalization or with shock were 72.79% and 55.68%, respectively. The mortality rate was 1.00%. . PICU hospitalization and shock rates of multisystem inflammatory syndrome in children associated with COVID-19 were high, and its cumulative multiorgans and inflammatory indicators are increased, but if treated in time, the mortality rate was low.
PubMed: 34336288
DOI: 10.1155/2021/5596727 -
Infection and Drug Resistance 2022The ongoing novel coronavirus disease 2019 (COVID-19) is triggering significant morbidity and mortality due to its contagious nature and absence of definitive... (Review)
Review
BACKGROUND
The ongoing novel coronavirus disease 2019 (COVID-19) is triggering significant morbidity and mortality due to its contagious nature and absence of definitive management. In Ethiopia, despite a number of primary studies have been conducted to estimate the case fatality rate (CFR) of COVID-19, no review study has attempted to summarize the findings to better understand the nature of pandemics and the virulence of the disease.
OBJECTIVE
To summarize the CFR of COVID-19 and factors contributing to mortality in Ethiopia.
METHODS
PRISMA guideline was followed. PubMed, Science Direct, CINAHL, SCOPUS, Hinari, and Google Scholar were systematically searched using pre-specified keywords. Observational studies ie, cohort, cross-sectional, and case-control studies were included. The Newcastle-Ottawa scale adapted for observational studies was used to assess the quality of included studies. CFR was defined as the proportion of COVID-19 cases with the outcome of death within a given period. Factors contributing to COVID-19 mortality at p-value <0.05 were described narratively from the eligible articles.
RESULTS
A total of 13 observational studies were included in this study. Consequently, this review confirmed the CFR of COVID-19 in Ethiopia ranges between 1-20%. Additionally, comorbid conditions, older age group, male sex, substance use, clinical manifestations (abnormal oxygen saturation level, atypical lymphocyte count, fever, and shortness of breath), disease severity, and history of surgery/trauma increased the likelihood of death from COVID-19 death.
CONCLUSION
This study shows that the range of CFR of COVID-19 in Ethiopia is almost equivalent to other countries, despite the country's low testing capacity and case detection rate in reference to its total population. Comorbid diseases, older age group, male sex, cigarette smoking, alcohol drinking, clinical manifestations and disease severity, and history of surgery/trauma were factors contributing to COVID-19 mortality in Ethiopia. Therefore, given the alarming global situation and rapidly evolving large-scale pandemics, urgent interdisciplinary interventions should be implemented in those vulnerable groups to lessen the risk of mortality. Furthermore, the CFR of COVID-19 should be estimated from all treatment and rehabilitation centers in the country, as underestimation could be linked to a lack of preparedness and mitigation. A large set of prospective studies are also compulsory to better understand the CFR of COVID-19 in Ethiopia.
PubMed: 35813083
DOI: 10.2147/IDR.S369266 -
Journal of Cutaneous Pathology Dec 2021Primary cutaneous gamma/delta (γδ) T-cell lymphoma (PCGDTCL) is a rare, aggressive peripheral T-cell lymphoma. There is evidence that patients with epidermotropic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Primary cutaneous gamma/delta (γδ) T-cell lymphoma (PCGDTCL) is a rare, aggressive peripheral T-cell lymphoma. There is evidence that patients with epidermotropic PCGDTCL may have an improved prognosis compared with those with only dermal and/or subcutaneous involvement.
METHODS
Systematic review of the literature and application of inclusion criteria yielded 48 manuscripts detailing the cases of 104 patients.
RESULTS
Of the 104 patients, 57 were male (51.4%) and 47 were female (48.5%) Based on provided histopathologic descriptions, 57 cases (54.8%) had no epidermotropism, 47 cases (45.2%) patients demonstrated any degree of epidermotropism, and 25 cases were predominantly epidermotropic (25/104, 24%). Five-year overall survivals for patients with no epidermotropism, any epidermotropism, and predominantly epidermotropic presentation were 32.8%, 28.9%, and 40.0%, respectively (p = 0.40). The most commonly performed immunohistochemical markers were CD3, CD4, CD8, CD5, CD7, CD30, CD56, TCR beta, TCR γ, and TCR δ. There was no statistically significant difference in immunophenotype between groups. Lesion morphology was described in the majority of cases (85/104, 80.9%); most cases presented as a combination of nodules, plaques, and tumors (77.4%). Several cases had more atypical presentations, including "mycosis-fungoides-like" and ulcerated.
CONCLUSION
In PCGDTCL, neither epidermotropism nor predominantly epidermotropic phenotype predict a better prognosis. In addition, the case report literature in dermatology and dermatopathology is rich and highly valuable.
Topics: Female; Humans; Intraepithelial Lymphocytes; Lymphoma, T-Cell, Cutaneous; Male; Skin Neoplasms
PubMed: 34151455
DOI: 10.1111/cup.14082 -
Journal of the American Board of Family... 2021The accuracy of individual symptoms, signs, and several easily obtainable hematologic parameters for diagnosing infectious mononucleosis (IM) still needs to be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The accuracy of individual symptoms, signs, and several easily obtainable hematologic parameters for diagnosing infectious mononucleosis (IM) still needs to be confirmed. Improving the diagnosis of IM based on the clinical findings could prompt physicians to identify better which patients need a diagnostic test for IM. This study performed a systematic review to determine the accuracy of symptoms, signs, and hematologic parameters in patients with suspected IM that used heterophile antibody test or viral capsid antigen tests as the reference standard.
METHODS
The PubMed database was searched for all relevant articles. Two reviewers reviewed all studies in parallel and assessed the quality of the selected studies using the quality assessment of diagnostic accuracy studies 2 (QUADAS-2) criteria. The pooled measures of diagnostic performance were calculated by bivariate meta-analysis for each clinical finding, which included sensitivity, specificity, likelihood ratios, the diagnostic odds ratios, and the area under the receiver operating characteristic curve.
RESULTS
Seventeen studies were included in our final analysis. The prevalence of IM ranged from 2.1% to 80% among prospective cohort studies. The presence of splenomegaly (positive likelihood ratio [LR+], 2.39; 95% confidence interval [CI], 1.11-5.51), palatal petechiae (LR+, 1.32-11.40), posterior cervical lymphadenopathy (LR+, 3.16; 95% CI, 1.45-5.20), and axillary or inguinal cervical lymphadenopathy (LR+, 3.05; 95 CI, 1.85-4.70) were moderately useful for ruling in IM. The most helpful hematologic parameters for ruling in IM include lymphocytes greater than 4 × 10/L and greater than 40% to 50%, or atypical lymphocytes greater than 40%. A combination of lymphocytes greater than 50% and atypical lymphocytes greater than 10% (LR+, 50.40; 95% CI, 8.43-162) was also found to be helpful to rule in disease. Most of the clinical findings have limited diagnostic value in ruling out the disease when absent.
CONCLUSIONS
Although most symptoms and signs were unhelpful, the likelihood of IM is appreciably increased by several examination findings. Hematologic parameters were more accurate than symptoms and signs. Since most clinical findings have limited diagnostic value in ruling out the disease, physicians should not rely on the absence of any individual symptom or clinical sign for ruling out IM.
Topics: Diagnostic Tests, Routine; Humans; Infectious Mononucleosis; Neck; Prospective Studies; ROC Curve; Sensitivity and Specificity
PubMed: 34772769
DOI: 10.3122/jabfm.2021.06.210217 -
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 -
Journal of Orthopaedics 2020Dual mobility (DM) constructs effectively reduce the risk of dislocation in revision and high risk primary total hip arthroplasty. However, modular DM designs require... (Review)
Review
BACKGROUND
Dual mobility (DM) constructs effectively reduce the risk of dislocation in revision and high risk primary total hip arthroplasty. However, modular DM designs require the use of a cobalt-chrome liner against a titanium cup which may induce corrosion, metal ions release, and associated biologic response. The purpose of this systematic review study was to collect all reported cases of serum metal ions after DM in the literature and ask the following questions: 1) what is the overall rate of significantly elevated Cobalt and Chromium metal ions and how do these levels change over time? 2) Does femoral head material composition influence serum metal ion levels? and 3) were there any atypical lymphocytic associated lesions after modular DM that required revision surgery?
METHODS
A systematic review was performed according to PRISMA guidelines. In addition to patient demographics, information specific to the performance of the DM implant were recorded including: cobalt and chromium serum ion levels and all reported timepoints, the material composition of the femoral head, all revision and reoperations and any failure related to corrosion of the DM bearing. A significant elevation in cobalt or chromium was defined as >1.0 or >1.6 mcg/L.
RESULTS
248 modular DM THAs were analyzed. The cumulative mean cobalt and chromium levels for all included studies was 0.47mcg/L and 0.53mcg/L, respectively. At final follow-up 13 patients (5.2%) had elevated cobalt ion levels and 4 patients (1.6%) had elevated chromium ion levels. Femoral head material composition trended towards but did not significantly increase serum ion levels. Ceramic heads had elevated cobalt and chromium ions in 4/135 (3%) of patients compared to metal heads which had elevated cobalt ions in 9/113 (8%) and elevated chromium ions in 0/113 (0%), (p = 0.09). There were no reoperations or revisions for metal related reactions at final follow-up (mean 27.4 months).
CONCLUSION
In this systematic review including 248 modular DM THAs, elevated serum cobalt ions were present in 5.2% of patients at a mean follow-up of 27.4 months. While a trend towards increased Cobalt serum ions with the use of cobalt chrome femoral heads, femoral head composition was not significantly associated with increased serum metal ion levels. At final follow-up, metal ion levels appear to decrease in the majority of patients between 1 and 2 years and no patient was revised for metal ion related complications. Continued serum metal ion surveillance is recommended to ensure the safety of DM constructs in THA with longer term follow-up.
PubMed: 32968337
DOI: 10.1016/j.jor.2020.08.019 -
European Review For Medical and... Jan 2021Many studies have been published recently on the characteristics of the clinical manifestations of COVID-19 in children. The quality scores of literature are different,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Many studies have been published recently on the characteristics of the clinical manifestations of COVID-19 in children. The quality scores of literature are different, and the incidence of clinical manifestations and laboratory tests results vary greatly. Therefore, a systematic retrospective meta-analysis is needed to determine the incidence of the clinical manifestations of COVID-19 in children.
MATERIALS AND METHODS
Data from databases, such as PubMed, Web of science, EMBASE, Johns Hopkins University, and Chinese databases were analysed from January 31, 2020 to October 20, 2020. High-quality articles were selected for analysis based on a quality standard score. A meta-analysis of random effects was used to determine the prevalence of comorbidities and subgroup meta-analysis to examine the changes in the estimated prevalence in different subgroups.
RESULTS
Seventy-one articles involving 11,671 children were included in the study. The incidence of fever, respiratory symptoms, gastrointestinal symptoms, asymptomatic patients, nervous system symptoms, and chest tightness was 55.8%, 56.8%, 14.4%, 21.1%, 6.7%, and 6.1%, respectively. The incidence of multisystem inflammatory syndrome was 6.2%. Laboratory examination results showed that lymphocytes decreased in 12% and leukocytes decreased in 8.8% of patients, whereas white blood cells increased in 7.8% of patients. Imaging showed abnormalities in 66.5%, and ground-glass opacities were observed in 36.9% patients. Epidemiological history was present in 85.2% cases; severe disease rate was 3.33%. The mortality rate was 0.28%.
CONCLUSIONS
The clinical symptoms of COVID-19 in children are mild, and laboratory indicators and imaging manifestations are atypical. While screening children for COVID-19, in addition to assessing patients for symptoms as the first step of screening, the epidemiological history of patients should be obtained.
Topics: COVID-19; Child; Child, Preschool; Humans; Retrospective Studies; Systemic Inflammatory Response Syndrome
PubMed: 33577071
DOI: 10.26355/eurrev_202101_24685