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Malaria Journal Nov 2019Malaria rapid diagnostic tests based on histidine-rich protein-2 have played a vital role in improving malaria case management and surveillance particularly in Africa,...
Systematic review of the status of pfhrp2 and pfhrp3 gene deletion, approaches and methods used for its estimation and reporting in Plasmodium falciparum populations in Africa: review of published studies 2010-2019.
BACKGROUND
Malaria rapid diagnostic tests based on histidine-rich protein-2 have played a vital role in improving malaria case management and surveillance particularly in Africa, where Plasmodium falciparum is predominant. However, their usefulness has been threatened by the emergence of gene deletion on P. falciparum histidine rich protein 2 (pfhrp2) and P. falciparum histidine rich protein 3 (pfhrp3). Use of standard and recommended methods is key for accurate investigation, confirmation and reporting of pfhrp2 and pfhrp3 gene deletion.
METHODS
A systematic review was conducted to assess the status, methods and approaches that have been used for investigation, confirmation and reporting of pfhrp2 and pfhrp3 gene deletion in Africa. An online search was done using PubMed and MEDLINE Google Scholar for all articles published in English on pfhrp2/3 gene deletion in Africa. Relevant articles that met the inclusion criteria were summarized and assessed based on the protocol recommended by the World Health Organization for confirmation and reporting of pfhrp2/3 gene deletion.
RESULTS
The search identified a total of 18 articles out of which 14 (77.7%) fulfilled the criteria for inclusion and were retained for review. The articles were distributed across 12 countries where the pfhrp2 and pfhrp3 gene deletion studies were conducted and reported. The level of pfhrp2/3 gene deletion across selected studies in Africa ranged from the highest 62% to the lowest 0.4%. There was wide variation in methods and approaches including study designs, size and sampling and whether both pfhrp2 and pfhrp3 double deletions or pfhrp2 single deletion were investigated, with a wide variation in laboratory methods.
CONCLUSION
Based on the review, there is evidence of the presence of pfhrp2/3 gene-deleted P. falciparum parasites in Africa. The approaches and methods used for investigation, confirmation and reporting of pfhrp2/3 deleted parasites have varied between studies and across countries. Countries that are considering plans to investigate, confirm and report pfhrp2/3 deletion should use recommended standard and harmonized methods to prevent unnecessary recommendations for costly switch of RDTs in Africa.
Topics: Africa; Antigens, Protozoan; Diagnostic Tests, Routine; Gene Deletion; Malaria, Falciparum; Plasmodium falciparum; Protozoan Proteins
PubMed: 31694718
DOI: 10.1186/s12936-019-2987-4 -
Malaria Journal Jan 2020In 2017, nearly 80% of malaria morbidity and mortality occurred in sub-Saharan African (SSA) countries and India. Rapid diagnostic tests (RDTs), especially those... (Meta-Analysis)
Meta-Analysis
Prevalence of Plasmodium falciparum field isolates with deletions in histidine-rich protein 2 and 3 genes in context with sub-Saharan Africa and India: a systematic review and meta-analysis.
BACKGROUND
In 2017, nearly 80% of malaria morbidity and mortality occurred in sub-Saharan African (SSA) countries and India. Rapid diagnostic tests (RDTs), especially those targeting histidine-rich protein 2 (PfHRP2) of Plasmodium falciparum, have become an important diagnostic tool in these malaria-endemic areas. However, the chances of RDT-oriented successful treatment are increasingly jeopardized by the appearance of mutants with deletions in pfhrp2 and pfhrp3 genes. This systematic review and meta-analysis determines the prevalence of field P. falciparum isolates with deletion in pfhrp2 and/or pfhrp3 genes and their proportion among false-negative results in the PfHRP2-based RDTs in SSA and India.
METHODS
Eight electronic databases were used for searching potentially relevant publications for the systematic review analysis, wherein the main methodological aspects of included studies were analysed and some missing links in the included studies were identified.
RESULTS
A total of 19 studies were included, 16 from SSA and 3 from India. The pooled prevalence of pfhrp2 deletions was 8 and 5% while 16 and 4% for pfhrp3 gene deletions in Africa and India, respectively. The pooled proportion of pfhrp2 gene deletions found among false negative PfHRP2-based RDTs results was about 27.0 and 69.0% in Africa and India, respectively.
CONCLUSIONS
This review study indicates a relatively high proportion of both pfhrp2/3 genes deletions in P. falciparum isolates and among false-negative malaria cases using PfHRP2-based RDT results in SSA and India. Recently the deletions in pfhrp2/3 genes have also been reported from two African countries (Nigeria and Sudan). This review emphasizes the importance of more extensive studies and standardization of studies addressing the pfhrp2/3 gene deletions in malarious areas.
Topics: Africa South of the Sahara; Antigens, Protozoan; False Negative Reactions; Gene Deletion; Genome, Protozoan; India; Malaria, Falciparum; Plasmodium falciparum; Prevalence; Protozoan Proteins
PubMed: 31992330
DOI: 10.1186/s12936-019-3090-6 -
Clinical & Translational Oncology :... May 2020The specific association between PTEN deletion or ERG rearrangement and the recurrence of prostate cancer (PC) treated with radical prostatectomy (RP) or brachytherapy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The specific association between PTEN deletion or ERG rearrangement and the recurrence of prostate cancer (PC) treated with radical prostatectomy (RP) or brachytherapy is still unelaborated. Therefore, we performed a comprehensive meta‑analysis to understand the impact of these factors on cancer recurrence.
METHODS
A comprehensive literature search was performed in November 2018 based on PUBMED, EMBASE and Web of science database. Hazard ratio (HR) for biochemical recurrence free (BRF) which was defined as a PSA greater than or equal to 0.4 ng/mL after RP or another therapy for any detectable PSA and recurrence-free survival (RFS) which defined the time from the beginning of treatment to the earliest occurrence of local recurrence, distant metastasis or death. Which were extracted from eligible studies. I value was used to assess the pooled heterogeneity.
RESULT
A total of 6744 patients from 17 studies were included in this analysis Overall, The pooled results showed that PTEN loss predict pooled BRF (HR 1.79, 95% CI 1.49-2.16, P < 0.001) and RFS (HR 1.71, 95% CI 1.50-1.95, P < 0.001) in patients after radical prostatectomy or brachytherapy for prostate cancer. Subgroup analysis revealed that PTEN deletion significantly predicted poor BRF or RFS in heterozygous studies group (HR 1.70, 95% CI 1.31-2.21, P < 0.001). The PTEN deletion also significantly predicted poor BRF or PFS in homozygous studies (HR 2.54, 95% CI 1.89-3.17, P < 0.001). And we had found that there was no significant association between ERG rearrangement and cancer recurrence regardless of PTEN loss or not. In addition, we concluded that Gleason score > 6 significantly predicted the poor BRF or RFS in studies, especially in Gleason score = 4 + 3 (HR 3.16, 95% CI 2.08-4.80, P < 0.01).
CONCLUSION
This study presented that PTEN deletion significantly reduce time of BRF or RFS, especially based on homozygous deletion. And we also found ERG rearrangement in tumor cell could not significantly predict BRF or RFS.
Topics: Gene Rearrangement; Humans; Male; Neoplasm Recurrence, Local; PTEN Phosphohydrolase; Prognosis; Prostatectomy; Prostatic Neoplasms; Sequence Deletion; Transcriptional Regulator ERG
PubMed: 31359337
DOI: 10.1007/s12094-019-02170-3 -
Medicine Jan 2020Non-small cell lung cancer (NSCLC) has a poor prognosis despite conventional treatments of surgery, radiotherapy, and chemotherapy. Small-molecule tyrosine kinase... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-small cell lung cancer (NSCLC) has a poor prognosis despite conventional treatments of surgery, radiotherapy, and chemotherapy. Small-molecule tyrosine kinase inhibitors acting on epidermal growth factor receptor (EGFR) have shown high efficacy and low toxicity for NSCLC. In particular, combining erlotinib with the VEGF antibody bevacizumab has therapeutic value in NSCLC, but the drugs' separate effects as monotherapy and any adverse outcomes of combination therapy remain unclear.
OBJECTIVES
To determine the efficacy and safety of erlotinib and bevacizumab for NSCLC, we conducted a meta-analysis and systematic review of randomized controlled trials.
DATA SOURCES
PubMed, Embase, Web of Science, and Cochrane databases were searched using keywords and manual review.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
We reviewed randomized controlled trials on the use of erlotinib combined with bevacizumab in adult patients with NSCLC, including data on outcome measures of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events.
STUDY APPRAISAL AND SYNTHESIS METHODS
After quality assessment, datasets were evaluated for heterogeneity. In the event of significant heterogeneity, a random-effects model was used to assess the overall outcome measures as a result of treatments. Subgroup analysis was conducted to evaluate the source of heterogeneity on PFS.
RESULTS
Compared with erlotinib or bevacizumab alone, the combined treatment did not significantly prolong OS (95% confidence interval [CI] = 0.84-1.11; P = .62) or increase the ORR (95% CI = 0.91-1.20; P = .52), but significantly improved PFS (95% CI = 0.58-0.73; P < .001). This improvement was especially notable in patients with the following characteristics: Eastern Cooperative Oncology Group Performance Status score of 0 or 1, female, no smoking history, adenocarcinoma, and EGFR Exon19 deletion or Exon21 Leu858Arg mutation. Combination therapy significantly increased incidence of grade 1-2 hypertension (20.3% vs 6.3%, 95% CI 1.73-5.88; P < .01) and severe diarrhea (10% vs 3.2%, 95% CI 1.36-6.60; P = .01).
LIMITATIONS
The low number of available randomized controlled trials could influence interpretation.
CONCLUSIONS
Compared with erlotinib or bevacizumab monotherapy, their combination effectively prolongs PFS but increases incidence of adverse events in NSCLC patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride; Humans; Lung Neoplasms; Randomized Controlled Trials as Topic
PubMed: 32011468
DOI: 10.1097/MD.0000000000018771 -
Frontiers in Oncology 2020In the Xuanwei region of China, lung cancer incidence and mortality are among the highest in China, attributed to severe air pollution generated by combustion of smoky...
BACKGROUND
In the Xuanwei region of China, lung cancer incidence and mortality are among the highest in China, attributed to severe air pollution generated by combustion of smoky coal. No study has yet comprehensively evaluated the prevalence of epidermal growth factor receptor () mutation characteristics in patients with non-small cell lung cancer (NSCLC) in Xuanwei. This meta-analysis was designed to analyze the mutation pattern in NSCLC patients in Xuanwei region of Yunnan Province in China.
METHODS
Electronic databases were comprehensively searched and relevant literatures were retrieved. The odds ratio (OR) for mutations between Xuanwei region and non-Xuanwei region was calculated, and the absolute incidence of mutations in Xuanwei was pooled by mutation subtype.
RESULTS
Seven studies involving 1,355 patients with NSCLC from Yunnan Province (442 in Xuanwei and 913 in other regions) were included. The mutation rate ranged between 30.19% and 55.56%. Higher uncommon mutations (OR: 5.69, 95%CI: 2.23-14.49, P<0.001) and lower common mutations (OR: 0.18, 95%CI: 0.07-0.45, P<0.001) were found in Xuanwei region, compared with non-Xuanwei region. Specifically, the uncommon mutation rate was 59.50% and common mutation rate was 40.50% in Xuanwei. The mutation incidence of exon 18 G719X (OR: 3.21, 95%CI: 1.48-6.97, P=0.003), exon 20 S768I (OR: 6.44; 95%CI: 2.66-15.60; P<0.001), and exon 18 G719X + 20 S768I (OR: 6.55; 95%CI: 1.92-22.33; P=0.003) in Xuanwei were significantly higher, while the frequency of 19 deletion (OR: 0.28, 95%CI: 0.11-0.77, P<0.001) and 21 L858R mutation (OR: 0.51, 95%CI: 0.31-0.84, P=0.007) were lower.
CONCLUSIONS
The results highlight the distinct mutation spectrum of NSCLC patients in Xuanwei region compared with other regions, with higher uncommon mutations but lower common mutations. The distinct Xuanwei featured genetic variations provide a unique model to further study carcinogenesis of lung cancer.
PubMed: 33224870
DOI: 10.3389/fonc.2020.519073 -
Thoracic Cancer Jul 2016The correlation between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and EGFR sensitive mutation subtypes in advanced or metastatic non-small...
Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is especially beneficial to patients with exon 19 deletion compared with exon 21 L858R mutation in non-small-cell lung cancer: Systematic review and meta analysis.
BACKGROUND
The correlation between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and EGFR sensitive mutation subtypes in advanced or metastatic non-small cell lung cancer (NSCLC) remains uncertain. We performed this meta-analysis to determine different clinical outcomes between patients with exon 19 deletion accepting EGFR-TKI therapy compared with those with exon 21 L858R mutation.
METHODS
PubMed and Web of Science were analyzed for eligible trials. Raw data were extracted to give pooled estimates of the effect of EGFR-TKI therapy on objective response rate (ORR), one-year progression-free survival (PFS), and two-year overall survival (OS).
RESULTS
We identified 13 eligible trials involving 912 patients. Prospective meta-analysis demonstrated that the ORR of the 19 deletion group was significantly higher than the 21 L858R mutation group (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.18-3.33; P = 0.01), but no statistical significance between the one-year PFS rate of the 19 deletion and 21 L858R groups (OR 1.44, 95% CI 0.96-2.18; P = 0.08) was found. However, retrospective meta-analysis demonstrated that a significantly higher one-year PFS rate was associated with the 19 deletion group (OR 1.73, 95% CI 1.17-2.56; P = 0.006). The two-year survival rate of the 19 deletion group was significantly higher than the 21 L858R group (OR 5.27, 95 % CI 1.76-15.71; P = 0.003).
CONCLUSIONS
In advanced NSCLC patients, an exon 19 deleton may provide superior ORR, PFS, and OS after EGFR-TKI treatment compared with an exon 21 L858R mutation.
PubMed: 27385982
DOI: 10.1111/1759-7714.12343 -
Frontiers in Oncology 2021Lung adenocarcinoma can transform into small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. Approximately 3% to 10% of epidermal...
Outcomes in Patients With Lung Adenocarcinoma With Transformation to Small Cell Lung Cancer After EGFR Tyrosine Kinase Inhibitors Resistance: A Systematic Review and Pooled Analysis.
BACKGROUND
Lung adenocarcinoma can transform into small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. Approximately 3% to 10% of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) could transform to SCLC. This phenomenon has been described in several case reports and small patient series. However, the characteristics and treatment outcomes of this population have not been comprehensively reported, and their clinical course is poorly characterized.
METHODS
We performed a systematic review of the published literature to summarize the clinical and pathological features and prognosis of the reported cases and analyzed the demographics, disease features, and outcomes.
RESULTS
A total of 72 patients (50 females and 22 males) initially diagnosed with lung adenocarcinoma were included. EGFR mutations included 19-deletion (75%), L858R (22%), and G719X (3%). All patients received EGFR-TKIs before SCLC transformation. The median time from diagnosis to transformation was 20.5 months (95% CI, 15.45 to 26.55 months). Of the 67 patients with post-translational gene test results, 58 maintained their EGFR mutation, and only 1 of 18 with prior T790M positivity retained T790M mutation. After the pathological transformation, both conventional chemotherapy regimen and chemotherapy combined targeted therapy yielded high response rates. The disease control rate of first-line therapy after transformation was 76%, while the objective response rate was 48%. The median overall survival (OS) since diagnosis was 27 months (95% CI, 22.90 to 31.10 months), whereas median OS since SCLC transformation was 8.5 months (95% CI, 5.50 to 11.60 months).
CONCLUSION
The prognosis of transformed SCLC is worse than primary SCLC. The response rate to conventional chemotherapy was high. However, the progression-free survival and OS after transformation were short and the prognosis was poor with first-line therapies. New therapies are needed in the management of transformed SCLC.
PubMed: 35223450
DOI: 10.3389/fonc.2021.766148 -
Orphanet Journal of Rare Diseases Jan 2023Woodhouse-Sakati syndrome (WSS) is a rare, autosomal recessive genetic disorder with variable clinical manifestations mainly affecting the endocrine and nervous systems.... (Review)
Review
BACKGROUND
Woodhouse-Sakati syndrome (WSS) is a rare, autosomal recessive genetic disorder with variable clinical manifestations mainly affecting the endocrine and nervous systems. The aim of this study was to systematically review the genetic basis of WSS and report the genetic variants and clinical phenotypes associated with the disease.
METHODS
PubMed, Science Direct, Scopus, and Web of Science databases were searched from the time of inception until June 2022. Broad search terms were used to capture the literature describing all genetic variants associated with WSS. The search keywords used are "Woodhouse Sakati" along with the term "mutation" OR "gene" OR "variant" OR "polymorphism".
RESULTS
Twenty-five eligible studies were included in this study. One hundred and eighty-five patients in 97 families from 12 different countries were diagnosed with WSS. In patients from the Greater Middle East (GME) region, consanguineous marriages were common (67%). Thirteen different DCAF17 variants were associated with WSS development (including 8 identified in the GME region). The most frequent variant was a frameshift deletion variant (c.436delC, p.Ala147Hisfs*9) unique to Arabs that was reported in 11 cases from Tunisia, Kuwait, Qatar, Bahrain, and Saudi Arabia. There were no clear genotype-phenotype correlations for the different variants.
CONCLUSIONS
This systematic review highlights the molecular basis and clinical manifestations of WSS globally, including the GME region, where the disease is prevalent due to consanguinity. Additional studies are now needed to understand the genotype-phenotype correlation for different DCAF17 variants and their impact on the phenotypic heterogeneity observed in WSS patients.
Topics: Humans; Molecular Epidemiology; Middle East; Diabetes Mellitus; Alopecia; Nuclear Proteins; Ubiquitin-Protein Ligase Complexes
PubMed: 36721231
DOI: 10.1186/s13023-023-02614-8 -
American Journal of Medical Genetics.... Jun 2023The 6p25 deletion syndrome is a rare genetic disorder characterized by a wide spectrum of congenital anomalies. Ophthalmic abnormalities appear to be highly associated...
The 6p25 deletion syndrome is a rare genetic disorder characterized by a wide spectrum of congenital anomalies. Ophthalmic abnormalities appear to be highly associated with the syndrome, although this relationship has not been well characterized to date. We conducted a systematic literature review to highlight the ocular features in patients with this deletion syndrome and describe a 7-month-old female who has a 6.07 MB 6p25.1p25.3 deletion and a 4.25 MB 17q25.3 duplication. Our patient presented with multiple congenital anomalies, including macrocephaly, frontal bossing, low set ears, tent-shaped mouth, saddle nose, flat midface, and hearing impairment. Her ophthalmic features included proptosis, down-slanting palpebral fissures, hypertelorism, nystagmus, bilateral posterior embryotoxon, and decentered and abnormally shaped pupils. A systematic review of the published cases with sufficient clinical eye descriptions included 63 cases with a confirmed 6p25 deletion. The most common eye findings observed were posterior embryotoxon, iris hypoplasia, corectopia, cornea opacity, and glaucoma.
Topics: Humans; Female; Infant; Chromosome Deletion; Eye Abnormalities; Glaucoma; Syndrome; Chromosomes
PubMed: 36941760
DOI: 10.1002/ajmg.a.63186 -
Clinical Rheumatology Dec 2017The association of thrombotic microangiopathy (TMA) with systemic lupus erythematosus (SLE) has been described in 0.5 to 10% of cases, and patients present worse... (Review)
Review
Use of eculizumab in a systemic lupus erythemathosus patient presenting thrombotic microangiopathy and heterozygous deletion in CFHR1-CFHR3. A case report and systematic review.
The association of thrombotic microangiopathy (TMA) with systemic lupus erythematosus (SLE) has been described in 0.5 to 10% of cases, and patients present worse outcome. TMA is described as the association of microangiopathic hemolytic anemia, thrombocytopenia, and an organ injury, frequently the kidney. This study describes a successful case of use of eculizumab in a patient with SLE and TMA refractory to standard therapy, and provides a literature review. Case description and search in PubMed and MEDLINE using systemic lupus erythemathous and/or antiphospholipid syndrome (APS) and eculizumab retrieved 15 case reports. Eighteen-year-old female presented acute renal failure and TMA and was diagnosed with SLE. Steroids and IV cyclophosphamide were started together with plasma exchange. After 55 days, she still persisted with microangiopathic anemia, thrombocytopenia, and anuria, and eculizumab was introduced. She had rapid improvement in hematological parameters, and dialysis was discontinued 25 days after the first dose. Genetic analysis showed large heterozygous deletion encompassing the entire CFHR1 and CFHR3, a finding previously associated with patients presenting atypical hemolytic-uremic syndrome (aHUS). Twenty patients who received eculizumab with SLE and/or APS have been published to date: 11 were female and mean age at presentation was 31 years. Seven out of the 20 patients presented only SLE, 5 patients only APS and 8 patients both SLE and APS. Eighteen patients underwent plasma exchange, with a mean of 20 (4-120) sessions per patient. Thirteen patients received rituximab. Hematological response was evident in 100% and kidney recovery in 85% of patients. The terminal complement blockade with eculizumab is an optional treatment for patients with SLE and/or APS presenting TMA and refractory to current immunosuppression therapies. Genetic testing may help recognize patients with aHUS and SLE/APS and therefore help to determine length of treatment with eculizumab.
Topics: Adolescent; Antibodies, Monoclonal, Humanized; Blood Proteins; Complement C3b Inactivator Proteins; Female; Humans; Lupus Erythematosus, Systemic; Sequence Deletion; Thrombotic Microangiopathies; Treatment Outcome
PubMed: 28905254
DOI: 10.1007/s10067-017-3823-2