Gastrointestinal stromal tumor in North Africa and the middle east: updates in presentation and management from an 11-year retrospective cohort.

OBJECTIVES: This study described the epidemiological, clinical, and survival profiles of patients with gastrointestinal stromal tumor (GIST) in North Africa and the Middle East (AfME). METHODS: This regional, multicenter, observational, retrospective study collected 11-year data on demographics, medical history, disease characteristics, current treatment approaches of GIST, the safety of the most common tyrosine kinase inhibitors (TKIs), second cancers, and survival status. RESULTS: Data of 201 eligible patients were analyzed: mean age was 56.9 ± 12.6 years; 111 (55.2%) patients were men, 21 (10.4%) patients had previous personal malignancy. The most common clinical presentation of GIST was dysphagia [92 (45.8%) patients]. The stomach was the most common primary site in 120 (60.7%) patients, 171 (85.1%) patients had localized disease at diagnosis. 198 (98.5%) GIST cases were CD117/CD34-positive. Imatinib was used in the neoadjuvant (18/21 patients), adjuvant (85/89 patients), and first-line metastatic treatment (28/33 patients) settings. The most common non-hematological toxicity associated with TKIs was vomiting in 32/85 (37.6%) patients. Overall, 100 (49.8%) patients (95%CI: 42.8-56.7%) were alive and disease-free while 30 (14.9%) patients were alive with active disease. CONCLUSION: Presentation of GIST in our AfME population is consistent with global reports, being more frequent in patients >50 years old and having the stomach as the most common primary site. Unlike what is usually reported, though, we did have more patients with lymphatic spread of the disease. Despite the global trend and advances in the treatment of GIST according to molecular profile, this is still far to happen in our population given the lack of access to molecular profiles and the high associated cost.

Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study.

Introduction: The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine. Methods: Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine. Results and discussion: Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants' CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.

Hematological indices reference intervals for a healthy Arab population in Qatar: Effect of age, gender, and geographic location.

ABSTRACT: Hematologic reference intervals vary with gender, age, ethnicity, and geographic area. Therefore, local or national laboratory reference ranges are essential to enhance the accuracy when diagnosing health conditions. Still, no comprehensive list of reference ranges tailored to the Arab population living in Qatar. Accordingly, this study aims at establishing a hematology reference guide for Arabs in Qatar.This is a retrospective study where 750 healthy volunteers (18-69 years) from 2015 to 2019 were included, analyzed by an automated hematology analyzer. Arab adults were divided into African (Egypt, Libya, Tunisia, Morocco) and Asian (Syria, Lebanon, Jordon, Palestine, Qatar). The Cell-Dyn and Sysmex were used for measuring hematological parameters.The mean +/- 2SD were established for all the study groups. Arab males had significantly higher Hb, Hct, red cell distribution width, absolute neutrophil count, lymphocytes, and monocyte counts than females. Asian-Arab males had significantly higher Hb concentration and higher WBC, lymphocytes, and eosinophils than African Arabs. Asian-Arab young (>18: < 40 years) males had significantly higher Hb and lymphocytes and lower monocytes than older males (>40 years). African-Arab young males had significantly higher lymphocytes and lower monocytes than older males. Asian-Arab young females had higher WBC and absolute neutrophil count than older Asian Arabs.The findings of this study will help in establishing specific reference intervals in the Arab world. The differences in hematology reference intervals considering age, gender, and geographical location highlight the importance of establishing blood reference intervals in each country considering the ethnic diversity of each country.

Environmental Factors, Lifestyle Risk Factors, and Host Characteristics Associated With Philadelphia Negative Myeloproliferative Neoplasm: A Systematic Review.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the overproduction of mature myeloid cells and are often associated with an acquired genetic mutation of Janus Kinase2V617F. Various epidemiological studies have indicated associations between environmental factors, lifestyle factors, and host characteristics with developing MPNs. This review aims to collect and summarize the existing information on these risk factors and establish their association with pathogenesis MPNs. Medline, Embase, PubMed, and grey literature were systematically searched using key terms for MPNs, and epidemiological study designs, that is, cross-sectional studies, case-control, and cohort, that investigated the risk factors for MPNs published were identified. Out of the 4621 articles identified, 20 met the selection criteria and were included in this review. Heterogeneity, study reliability, and bias were assessed. A significant association was found between smoking and the development of MPNs. This relationship has been explained by the substantial increase in several proinflammatory mediators and systematic oxidative stress causing hyperstimulation of myeloid compartments leading to the development of MPNs. Obesity was modestly linked with an increased risk of MPNs. The underlying mechanisms have been linked to changes in endocrine, metabolic, and inflammatory systems. No strong association was found between exposure to hazardous substances, that is, benzene and MPNs, but further investigation on the effects of increased levels and duration of exposure on hematopoietic stem cells will be beneficial. Unique individual and host variations have been determined as a modifier of disease pathogenesis and phenotype variations. There is a higher incidence rate of females developing MPNs, specifically ET, than males with higher PV incidence. Therefore, gender contributes to the heterogeneity in myeloproliferative neoplasm. Studies identified as part of this review are very diverse. Thus, further in-depth assessment to explore the role of these etiological factors associated with MPNs is warranted.

Persistent anti-NY-ESO-1-specific T cells and expression of differential biomarkers in a patient with metastatic gastric cancer benefiting from combined radioimmunotherapy treatment: a case report.

Combined radioimmunotherapy is currently being investigated to treat patients with cancer. Anti-programmed cell death-1 (PD-1) immunotherapy offers the prospect of long-term disease control in solid tumors. Radiotherapy has the ability to promote immunogenic cell death leading to the release of tumor antigens, increasing infiltration and activation of T cells. New York esophageal squamous cell carcinoma-1 (NY-ESO-1) is a cancer-testis antigen expressed in 20% of advanced gastric cancers and known to induce humoral and cellular immune responses in patients with cancer. We report on the dynamic immune response to the NY-ESO-1 antigen and important immune-related biomarkers in a patient with metastatic gastric cancer treated with radiotherapy combined with anti-PD-1 pembrolizumab antibody.Our patient was an 81-year-old man diagnosed with locally advanced unresectable mismatch repair-deficient gastric cancer having progressed to a metastatic state under a second line of systemic treatment consisting of an anti-PD-1 pembrolizumab antibody. The patient was subsequently treated with local radiotherapy administered concomitantly with anti-PD-1, with a complete response on follow-up radiologic assessment. Disease control was sustained with no further therapy for a period of 12 months before relapse. We have identified an NY-ESO-1-specific interferon-γ (IFN-γ) secretion from the patients' T cells that was significantly increased at response (****p˂0.0001). A novel promiscuous immunogenic NY-ESO-1 peptide P39 (P153-167) restricted to the four patient's HLA-DQ and HLA-DP alleles was identified. Interestingly, this peptide contained the known NY-ESO-1-derived HLA-A2-02:01(P157-165) immunogenic epitope. We have also identified a CD107+ cytotoxic T cell subset within a specific CD8+/HLA-A2-NY-ESO-1 T cell population that was low at disease progression, markedly increased at disease resolution and significantly decreased again at disease re-progression. Finally, we identified two groups of cytokines/chemokines. Group 1 contains five cytokines (IFN-γ, tumor necrosis factor-α, interleukin-2 (IL-2), IL-5 and IL-6) that were present at disease progression, significantly downregulated at disease resolution and dramatically upregulated again at disease re-progression. Group 2 contains four biomarkers (perforin, soluble FAS, macrophage inflammatory protein-3α and C-X-C motif chemokine 11/Interferon-inducible T Cell Alpha Chemoattractant that were present at disease progression, significantly upregulated at disease resolution and dramatically downregulated again at disease re-progression. Combined radioimmunotherapy can enhance specific T cell responses to the NY-ESO-1 antigen that correlates with beneficial clinical outcome of the patient.

Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report.

Targeting the programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway has been shown to enhance T cell-mediated antitumor immunity. Clinical responses are limited to subgroups of patients. The search for biomarkers of response is a strategy to predict response and outcome of PD-1/PD-L1 checkpoint intervention. The NY-ESO-1 cancer testis antigen has been considered as a biomarker in head and neck squamous cell carcinoma (HNSCC) patients and can induce both specific NY-ESO-1 antibody and T cells responses. Here, we correlated clinical responsiveness to anti-PD-1 (nivolumab) treatment with immunity to NY-ESO-1 in a patient with recurrent HNSCC. The patient was treated with second-line treatment of nivolumab and had a stable disease for over 7 months. His NY-ESO-1 antibody was found to be lower after the third (****p < 0.0001) and the fifth (****p < 0.0001) cycles of treatment compared to base line, and this was in line with the stability of the disease. The NY-ESO-1-specific T cells response of the patient was found to be increased after the third and the fifth (**p = 0.002) cycles of treatment but had a significant decline after progression (**p = 0.0028). The PD-1 expression by the patient's T cells was reduced 15-folds after nivolumab treatment and was uniquely restricted to the CD8+ T cells population. Several cytokines/chemokines involved in immune activation were upregulated after nivolumab treatment; two biomarkers were reduced at progression [interleukin (IL)-10: ****p < 0.0001 and CX3CL1: ****p < 0.0001]. On the other hand, some cytokines/chemokines contributing to immune inhibition were downregulated after nivolumab treatment; two biomarkers were increased at progression (IL-6: ****p < 0.0001 and IL-8: ****p < 0.0001). This data support the notion that the presence of anti-NY-ESO-1 integrated immunity and some cytokines/chemokines profile may potentially identify a response to PD-1 blockade in HNSCC patients.

A wearable wound moisture sensor as an indicator for wound dressing change: an observational study of wound moisture and status.

Wound moisture is known to be a key parameter to ensure optimum healing conditions in wound care. This study tests the moisture content of wounds in normal practice in order to observe the moisture condition of the wound at the point of dressing change. This study is also the first large-scale observational study that investigates wound moisture status at dressing change. The WoundSense sensor is a commercially available moisture sensor which sits directly on the wound in order to find the moisture status of the wound without disturbing or removing the dressing. The results show that of the 588 dressing changes recorded, 44·9% were made when the moisture reading was in the optimum moisture zone. Of the 30 patients recruited for this study, 11 patients had an optimum moisture reading for at least 50% of the measurements before dressing change. These results suggest that a large number of unnecessary dressing changes are being made. This is a significant finding of the study as it suggests that the protocols currently followed can be modified to allow fewer dressing changes and less disturbance of the healing wound bed.