Sulfuric acid-induced skin neoplasms in immunocompetent mice.

This study investigates the carcinogenic potential of chronic dermal exposure (16 weeks) to sulfuric acid (SA) in immunocompetent mice. Clinical assessments, histopathological analyses, immunohistochemical analyses and biochemical assays were conducted to evaluate skin irritation, oxidative stress biomarkers and the potential carcinogenic effect of SA. Results indicated that prolonged exposure to SA leads to various alterations in skin structure, notably inflammation, preneoplastic and neoplastic proliferation in hair follicles, as well as hyperkeratosis and acanthosis, resulting in an increased epidermal thickness of 98.50 ± 21.6 µm. Immunohistochemistry analysis further corroborates these observations, showcasing elevated nuclear expression of p53 and Ki-67, with a significant mitotic index of (57.5% ± 2.5%). Moreover, biochemical analyses demonstrate that SA induces lipid peroxidation in the skin, evidenced by a high level of Malondialdehyde and a consequential reduction in catalase activity. These findings suggest that prolonged exposure to SA can induce skin neoplasms, highlighting the need for stringent safety measures in environments where SA is frequently used. This study underscores the potential occupational health risks associated with SA exposure.

PrEPare_Morocco a successful community-based PrEP delivery demonstration program for men who have sex with men and female sex workers in Morocco.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention tool, recommended for persons at substantial risk for HIV, such as female sex workers (FSW) and men who have sex with men (MSM). We present Morocco's and the Middle East/North Africa's first PrEP demonstration project. Our pilot aimed to assess the feasibility and acceptability of a community-based PrEP program for FSW and MSM in Morocco's highest HIV prevalence cities: Agadir, Marrakech, and Casablanca. From May to December 2017, 373 eligible participants engaged in a 5-9 month program with daily oral TDF/FTC and clinic visits. Of these, 320 initiated PrEP, with 119 retained until the study's end. We report an 86% PrEP uptake, 37% overall retention, and 78% retention after 3 months. No seroconversions occurred during follow-up. These results underscore PrEP's need and acceptability among MSM and FSW and demonstrate the effectiveness of a community-based PrEP program in Morocco. These findings informed Morocco's current PrEP program and hold potential for the wider region with similar challenges.

Exploring the multifaceted effects of Ammi visnaga: subchronic toxicity, antioxidant capacity, immunomodulatory, and anti-inflammatory activities.

Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.

CXCL-8 as a signature of severe Helicobacter pylori infection and a stimulator of stomach region-dependent immune response.

Helicobacter pylori infection is involved in development of diverse gastro-pathologies. Our aim is to investigate potential signature of cytokines-chemokine levels (IL-17A, IL-1ß, and CXCL-8) in H. pylori-infected patients and their impact on immune response in both corpus and antrum. Multivariate level analysis with machine learning model were carried out using cytokines/chemokine levels of infected Moroccan patients. In addition, Geo dataset was used to run enrichment analysis following CXCL-8 upregulation. Our analysis showed that combination of cytokines-chemokine levels allowed prediction of positive H. pylori density score with <5% of miss-classification error, with fundus CXCL-8 being the most important variable for this discrimination. Furthermore, CXCL-8 dependent expression profile was mainly associated to IL6/JAK/STAT3 signaling in the antrum, interferons alpha and gamma responses in the corpus and commonly induced transcriptional /proliferative activities. To conclude, CXCL-8 level might be a signature of Moroccan H. pylori-infected patients and an inducer of regional-dependent immune response at the gastric level. Larger trials must be carried out to validate the relevance of these results for diverse populations.

The Clinicopathological Features and Prognostic Significance of HER2-Low in Early Breast Tumors Patients Prognostic Comparison of HER-Low and HER2-Negative Breast Cancer Stratified by Hormone Receptor Status.

Introduction: There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations. Methods: We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records. Results: Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival (p = 0.003) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival (p < 0.001). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors (p = 0.008). Conclusion: Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses.

The influence of Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-17, TNF-A, MIF, STAT3 on lung cancer risk in Moroccan population.

To date, several studies have reported that key cytokines in the inflammatory system have important roles in the pathogenesis of cancer, notably in lung cancer. The aim of this case-control study, conducted for the first time in Moroccan population, was to investigate and to analyze the association of the following inflammatory cytokine genes Interleukin (IL)-6, Interleukin (IL)-8, Interleukin (IL)-10, Interleukin (IL)-17, Tumor Necrosis Factor-Alpha (TNFA), Macrophage migration Inhibitory Factor (MIF) and Signal Transducer and Activator of Transcription 3 (STAT3) with lung cancer risk in our patients. Firstly, the mRNA expression was assessed by a quantitative real time PCR in the peripheral blood of lung cancer patients and healthy subjects. Secondly, polymorphisms in the genes encoding cytokines were assessed in 160 lung cancer patients and 150 healthy controls. Genotyping analysis was performed with a Real-Time polymerase chain reaction using TaqMan® genotyping assays on a 7500 FAST Real-Time PCR System and Restriction Fragment Length PolymorphismPCR. Our results revealed a significant difference in mRNA expression levels of IL-6, IL-8, IL-10, IL-17 and TNFA genes in lung cancer patients compared to healthy subjects (P < 0.05). Among the studied genes, we found a significant association between lung cancer risk in our patients and the following polymorphisms IL-6 (rs1800795, rs1800796), IL-8 (rs4075, rs2227306), IL-17F (rs763780, rs2397084) and MIF (rs755622). In conclusion, the results of our study suggest that IL-6, IL-8, IL-10, IL-17 and MIF cytokine genes may aggravate lung cancer risk in the Moroccan population. However, further investigations are required to confirm our findings.

Acceptability and usability of oral fluid-based HIV self-testing among female sex workers and men who have sex with men in Morocco.

BACKGROUND: In 2020, almost 20% of people living with HIV (PLHIV) in Morocco are still unaware of their HIV status. Under these circumstances, HIV self-test (HIVST) can be an efficient additional tool for improving the testing rates in Morocco and reaching the first objective of the UNAIDS 95-95-95 goal. ALCS, a Community-based organization, involved in HIV Testing since 1992, and the Ministry of Health of Morocco conducted, a study on the acceptability and usability of HIVST among Female sex workers (FSW) and MSM (men who have sex with men), using a salivary rapid test. To our knowledge, this is the first study in Morocco exploring these parameters. METHODS: We conducted a pilot study on the usability of the OraQuick HIV-1/2 salivary self-test among MSM and FSW visiting the ALCS centers for standard HIV rapid testing in five Moroccan cities. Participants chose whether or not to be assisted by lay provider HIV testing. The counselors sampled them to perform a standard rapid test and then invited them to a private room to perform the HIV self-test simultaneously. In addition, a questionnaire was administered to collect socio-demographic data and to assess their opinion about the usability of the salivary HIVST. RESULTS: Our study was carried out for 5 months and included 492 participants (257 MSM and 233 FSW). The average age of the participants was 29 years among MSM vs 34 years among FSW. The FSW have a lower educational level, 28,8% of them are Illiterate vs. 6,1% of the MSM. Only 18% of participants were aware of the existence of the HIVST, nevertheless, we recorded a very high rate of acceptability (90,6%) of the HIVST. Performing the HIVST was deemed very easy for 92,2% of MSM versus 80,6% of FSW. Although it was found very difficult for six participants, including five FSW, 4 of them could not read or write. Overall, the study registered a high HIV positivity rate (3,8%) and 100% of concordance between HIVST participants' interpretation and standard HIV testing performed by ALCS lay provider HIV testing. CONCLUSION: Our study shows very high acceptability of HIVST among FSWs and MSM in Morocco, HIV self-testing is still unknown by key populations in Morocco, and the low level of education of FSWs may be a barrier to the use of this test, but with the proposed assistance and adapted demonstration tools, the HIV self-testing will certainly improve access to testing in Morocco.

Fear of stigma from health professionals and family/neighbours and healthcare avoidance among PLHIV in Morocco: results from the Stigma Index survey Morocco.

BACKGROUND: Enacted or anticipated stigma among people living with HIV (PLHIV) can negatively impact healthcare engagement. We identified factors associated with having avoided HIV health services for fear of stigma among PLHIV in Morocco. METHODS: The Stigma Index survey was conducted in Morocco in March-June 2016. Factors associated with avoiding HIV testing and treatment services for fear of stigma by (A) health personnel or family/neighbours and (B) health personnel and family/neighbours compared to people who did not avoid health services for fear of stigma from either of the two sources were assessed using multinomial logistic regression models. RESULTS: Among 583 respondents, 280 (48.0%) were women and median number of years living with HIV was 5[IQR:2-7]. Half of the respondents reported avoiding health services for fear of stigma by health personnel and/or family/neighbours: (A) n = 228, 39.1% and (B) n = 68, 11.7%. After adjustment on perceived health status, not having had easy access to antiretroviral treatment ((A) aRR [95% CI] = 1.76[1.16; 2.68]; (B) 2.18[1.11; 4.27]), discrimination by PLHIV ((A) 1.87[1.12; 3.13]; (B) 3.35[1.63; 6.88]) and exclusion from social activities ((A) 1.70[1.10; 2.61]; (B) 2.63[1.39; 5.00]) were associated with having avoided health services for fear of stigma by health personnel or/and family/neighbours. Being female (2.85[1.48; 5.47]), not having been referred for an HIV test for suspected symptoms 3.47[1.67; 7.22], having discussed sexual/reproductive health with a health professional (4.56[2.38; 8.71]), and not having the feeling to influence decisions on local projects for PLHIV (3.47[1.37; 7.83], were associated with having avoided health services for fear of stigma by both sources. CONCLUSION: Results suggest a cumulative effect of fear of stigma and discrimination among PLHIV in Morocco. PLHIV who have experienced discrimination may seek to avoid similar situations at the expense of their health. These results should inform multi-level interventions and broader advocacy efforts to reduce stigma and discrimination.

Determinants and effects or consequences of internal HIV-related stigma among people living with HIV in Morocco.

BACKGROUND: HIV-related stigma and discrimination constitute a barrier to different intervention programs. Unlike external stigma, internal stigma is not well explored in in the Middle East and North African countries, while grasping this particular form of stigma is essential to limit its effects. The present study aims to measure internal stigma effects and to identify factors associated with this kind of stigma not yet documented among people living with HIV (PLHIV) in Morocco. METHODS: The PLHIV Stigma Index questionnaire (adapted and translated into French and Moroccan Arabic dialect "darija") was used to collect information regarding the stigma and discrimination experienced by PLHIV across 8 cities in Morocco (September-October 2016). A randomly drawn cluster of 10 PLHIV, consisting of 5 men and 5 women, was drawn at each participating medical care center to achieve a nationally representative sample of PLHIV. Fifteen interviewers living with HIV and five supervisors were selected and trained to administer the questionnaire. An internal stigma score (range: 0-7), was calculated based on seven negative feelings/ beliefs. Negative binomial regression was used to identify characteristics associated with the internal stigma score. RESULTS: Among 626 PLHIV, internal stigma was reported by 88.2%. The median [IQR] internal stigma score was 4 [2-5]. Regarding internal stigma, 51% avoided going to the local clinic when needed and 44% chose not to attend social gatherings. Belonging to at least one key population (aIRR [95%CI] = 1.15 [1.03; 1.28]), experiencing discriminatory reactions from family following HIV status disclosure (1.28 [1.11; 1.49]), avoiding HIV services for fear of stigmatization by staff (1.16 [1.05; 1.28]) and being denied health services because of HIV status (1.16 [1.03;1.32]), are among the factors significantly associated with an increase of the internal stigma score. CONCLUSIONS: Internal stigma is high among Moroccan PLHIV and significantly impacting their life decisions and their healthcare access. Multi-level interventions are needed to address internal stigma experienced by PLHIV in Morocco.

Risk factors for inflammatory and non-inflammatory breast cancer in North Africa.

PURPOSE: Studies of the etiology of inflammatory breast cancer (IBC), a rare but aggressive breast cancer, have been hampered by limited risk factor information. We extend previous studies by evaluating a broader range of risk factors. METHODS: Between 2009 and 2015, we conducted a case-control study of IBC at six centers in Egypt, Tunisia, and Morocco; enrolled were 267 IBC cases and for comparison 274 non-IBC cases and 275 controls, both matched on age and geographic area to the IBC cases. We administered questionnaires and collected anthropometric measurements for all study subjects. We used multiple imputation methods to account for missing values and calculated odds ratios (ORs) and 95% confidence intervals (CIs) using polytomous logistic regression comparing each of the two case groups to the controls, with statistical tests for the difference between the coefficients for the two case groups. RESULTS: After multivariable adjustment, a livebirth within the previous 2 years (OR 4.6; 95% CI 1.8 to 11.7) and diabetes (OR 1.8; 95% CI 1.1 to 3.0) were associated with increased risk of IBC, but not non-IBC (OR 0.9; 95% CI 0.3 to 2.5 and OR 0.9; 95% CI 0.5 to 1.6 for livebirth and diabetes, respectively). A family history of breast cancer, inflammatory-like breast problems, breast trauma, and low socioeconomic status were associated with increased risk of both tumor types. CONCLUSIONS: We identified novel risk factors for IBC and non-IBC, some of which preferentially increased risk of IBC compared to non-IBC. Upon confirmation, these findings could help illuminate the etiology and aid in prevention of this aggressive cancer.

Gastric IL-1ß, IL-8, and IL-17A expression in Moroccan patients infected with Helicobacter pylori may be a predictive signature of severe pathological stages.

INTRODUCTION: Helicobacter pylori induces acute gastritis that can progress to serious diseases such as gastric cancer. H. pylori interacts with host cells within the gastric mucosa, resulting in activation of multiple innate immune signalling pathways, leading to pro-inflammatory cytokines production and immune cells recruitment. Various studies have shown that there are ethnic- and population-related differences in the expression of these cytokines. Although the H. pylori infection is a major public health problem in Morocco, to our knowledge, no study has been carried out in gastric cytokine expression from H. pylori-infected Moroccan patients. Thus we aimed to (i) determine the IL-1ß, IL-8 and IL-17A gene expression in gastric biopsies from Moroccan patients infected with H. pylori, and (ii) to determine the cytokine signature of each pathological stages associated with this infection. MATERIAL AND METHODS: 71 patients with epigastralgic pain were included in this study. The H. pylori detection on gastric biopsies was performed by histopathological and PCR analysis. The IL-1ß, IL-8 and IL-17A mRNA expression in the antrun and fundus biopsies was performed by RT-qPCR. RESULTS: The histopathological and PCR analyses revealed that 87.32% of the patients were infected with H. pylori. IL-1ß mRNA expression was significantly lower in the antral mucosa of H. pylori-infected patients (p = 0.0038) than in the uninfected while there was no significant difference in the expression of IL-8 and IL-17A mRNA. The expression of the three cytokines was higher in the fundic mucosa of H. pylori-infected patients than in the uninfected patients, but only IL-8 and IL-17A expression reached statistical significance (p = 0.042 and p = 0.0179 respectively). Furthermore, the multivariate predictive analysis highlighted a cytokine signature that may predict metaplasia during the infection progression that involves a specific down-regulation of IL17A and an up-regulation of IL1ß in antral and fundic metaplasia respectively.

Clinico-pathologic and mammographic characteristics of inflammatory and non-inflammatory breast cancer at six centers in North Africa.

PURPOSE: We describe the clinico-pathologic and mammographic characteristics of inflammatory breast cancer (IBC) and non-IBC cases enrolled in a case-control study. Because IBC is a clinico-pathologic entity with rapid appearance of erythema and other signs, its diagnosis is based on clinical observation and thus, by necessity, subjective. Therefore, we evaluate our cases by photographic review by outside expert clinicians and by degree of adherence to the two most recent definitions of IBC: the international expert panel consensus statement and American Joint Committee on Cancer (AJCC) 8th edition (we used the slightly less restrictive 7th edition definition for our study). METHODS: We enrolled 267 IBC and 274 age- and geographically matched non-IBC cases at 6 sites in Egypt, Tunisia, and Morocco in a case-control study of IBC conducted between 2009 and 2015. We collected clinico-pathologic and mammographic data and standardized medical photographs of the breast. RESULTS: We identified many differences between IBC and non-IBC cases: 54.5% versus 68.8% were estrogen receptor-positive, 39.9% versus 14.8% human epidermal growth factor receptor 2-positive, 91% versus 4% exhibited erythema, 63% versus 97% had a mass, and 57% versus 10% had mammographic evidence of skin thickening. Seventy-six percent of IBC cases adhered to the expert panel consensus statement and 36% to the AJCC definition; 86 percent were confirmed as IBC by either photographic review or adherence to the consensus statement. CONCLUSIONS: We successfully identified distinct groups of IBC and non-IBC cases. The reliability of IBC diagnosis would benefit from expert review of standardized medical photographs and associated clinical information.

Association of Variants in IL6-Related Genes with Lung Cancer Risk in Moroccan Population.

PURPOSE: Lung cancer is known to be a complex multifactorial disease, involving both genetic and environmental factors. The study of the different signaling pathways and the identification of the genes involved, will contribute to further understanding the pathogenesis of the disease, thus allowing the development of appropriate targeted treatments. Recently, the link between cancer and inflammation has become more evident and inflammation has been proposed as the seventh hallmark of cancer. Previous studies have suggested that key cytokines involved in inflammation may have an important role in the etiology of lung cancer. The aim of this study was to investigate whether common variants in inflammation-related genes: IL-6, IL6-R, and IL6-ST, influence lung cancer risk in Moroccan population. MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs) in IL-6, IL6-R, and IL6-ST genes were assessed in 120 controls and 120 patients with confirmed lung cancer diagnosis. Genotyping analysis was performed with the TaqMan® allelic discrimination technology. The results were analyzed using SPSS 24.0 software. RESULTS: Among the studied SNPs, we found a significant association for the IL-6 (rs2069840) (OR = 1.63; 95% confidence interval 1.08-2.47; p = 0.01). No significant association was observed for the remaining SNPs of IL-6R (rs2228145) and IL-6ST (rs2228044) genes. CONCLUSION: Our results suggest the IL-6 (rs2069840) polymorphism may influence the occurrence of lung cancer in Moroccan patients.

[Astroblastoma: A rare glial tumor]. / L'astroblastome : une tumeur gliale rare.

Astroblastoma is a rare neuroepithelial tumor most commonly seen in children and young adults. Due to its rarity, this tumor can be easily misdiagnosed as its classification, histogenesis and therapeutic management are still being discussed. We report the case of a 21 year old man, who presented at the Emergency Room for loss of consciousness. He reported a history of headaches, vomiting and decreased visual acuity. The CT and MRI showed a left temporoparietal solid-cystic mass with heterogeneous enhancement and perilesional edema. The patient underwent a total mass resection. On histopathological examination, tumor cells were organized in perivascular pseudorosettes which are typically encountered in astroblastoma, without neither necrosis nor endothelial hyperplasia. They had broad processes and rounded nuclei without any mitotic activity. Immunochemistry stains confirmed the diagnosis by showing a positive reactivity for GFAP, EMA, vimentin and S100. Astroblastoma is a rare glial tumor of uncertain origin. Clinical presentation and imaging are nonspecific. Therefore, its diagnosis is based on histopathologic findings: typical perivascular pseudorosettes. However, similar histological pattern may be seen in other glial neoplasms. In the 2016 WHO Classification, astroblastoma is among the "other glial neoplasms" without a grading system. So far, there are no reliable prognosis factors for this tumor; however, two entities have been described: well differenciated astroblastoma (considered as low grade) and anaplastic/malignant astroblastomas (considered as high grade). Gross total resection is the treatment of choice for astroblastomas. Adjuvant therapy is still controversial. This case illustrates a cerebral tumor which is rarely encountered in practice and that can cause diagnostic problems and subsequently, inadequate treatment.

Chronic Mastitis in Egypt and Morocco: Differentiating between Idiopathic Granulomatous Mastitis and IgG4-Related Disease.

Idiopathic granulomatous mastitis (IGM) is a benign, frequently severe chronic inflammatory lesion of the breast. Its etiology remains unknown and reported cases vary in their presentation and histologic findings with an optimal treatment algorithm yet to be described owing mainly to the disease's heterogeneity. IgG4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition characterized by a dense lymphoplasmacytic infiltrate with many IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Immunosuppressive therapy is considered to be an effective first-line therapy for IgG4-RD. We sought to clarify and classify chronic mastitis according to the histologic findings of IgG4-RD mastitis with respect to IGM and to develop a robust diagnostic framework to help select patients for optimal treatment strategies. Using the largest collection to date (43 cases from Egypt and Morocco), we show that despite sharing many features, IGM and IgG4-RD mastitis are separate diseases. To diagnostically separate the diseases, we created a classification schema-termed the Michigan Classification-based upon our large series of cases, the consensus statement on IgG4-RD, and the histologic description of IGM in the literature. Using our classification, we discerned 17 cases of IgG4-RD and 8 cases of IGM among the 43 chronic mastitis cases, with 18 indeterminate cases. Thus, our Michigan Classification can form the basis of rational stratification of chronic mastitis patients between these two clinically and histopathologically heterogeneous diseases.

Clinicopathological characteristics and tumor infiltrating immune cells associations of PD-L1 tumor expression in non-small cell lung cancer patients.

AIM: Our study aimed to perform on Moroccan patients' non-small cell lung carcinoma (NSCLC) concerning the relationship between PD-L1 tumor expression, clinicopathological features and tumor infiltrating immune cells (ICs). METHODS: This is a retrospective study (2019 to 2021) conducted on samples from Moroccan patients with NSCLC at the Pathological Anatomy Laboratory of Ibn Rochd University Hospital in Casablanca. Eligible participants for our study had to meet the following predefined criteria: age ≥18 years, histologically confirmed NSCLC, no prior therapeutic interventions, availability of clinical and pathological data, and a usable tumor sample for determining PD-L1 status. Exclusion criteria applied to patients with other types of lung cancer and unusable tumor samples. The evaluation of tumor and immune expression of PD-L1 was performed using immunohistochemistry (IHC), with the 22C3 clone on the Dako Autostainer Link 48 platform. Tumor PD-L1 expression was categorized into 3 levels: TPS <1% (negative expression), TPS 1-49% (low expression), and TPS ≥50% (high expression). ICs infiltrating the tumor expressing PD-L1 were considered positive when more than 1% of positive ICs were present. RESULTS: Among the 316 analyzed samples, 56.6% showed a negative expression of PD-L1, 16.8% displayed a low expression of PD-L1, and 26.6% exhibited a strong expression. Regarding the histological type, among patients with TPS ≥ 50%, 25.8% had adenocarcinoma. Among patients with TPS ≥ 50%, 24.81% were smokers. PD-L1 was also strongly expressed in the lung (28.2%) and bronchi (26.5%). PD-L1 expression (TPS ≥ 50%) was observed in 35.29% of early-stage patients. Concerning tumor cells (TCs), 27.5% of tumors infiltrated by ICs had TPS ≥ 50%. Furthermore, coexpression of PD-L1 on both TCs and ICs infiltrating the tumor was found in 27.8% of tumors. Statistical analysis demonstrated a significant association between tumor PD-L1 expression and smoking status (P=0.019). However, no significant difference was observed between PD-L1 expression and the presence of ICs infiltrating the tumor (P=0.652), as well as the IHC expression of PD-L1 on ICs (P=0.259). CONCLUSION: Our results demonstrate a significant association between PD-L1 expression and smoking status. However, no significant association was observed between PD-L1 expression and the presence of infiltrating ICs, nor with the IHC expression of PD-L1 on ICs. Our data underscore the importance of participating in the study of specific factors influencing PD-L1 expression in patients with NSCLC.

Glioblastoma Vaccines as Promising Immune-Therapeutics: Challenges and Current Status.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard treatments including surgical resection, radiotherapy, and chemotherapy, have failed to significantly improve the prognosis of glioblastoma patients. Currently, immunotherapeutic approaches based on vaccines, chimeric antigen-receptor T-cells, checkpoint inhibitors, and oncolytic virotherapy are showing promising results in clinical trials. The combination of different immunotherapeutic approaches is proving satisfactory and promising. In view of the challenges of immunotherapy and the resistance of glioblastomas, the treatment of these tumors requires further efforts. In this review, we explore the obstacles that potentially influence the efficacy of the response to immunotherapy and that should be taken into account in clinical trials. This article provides a comprehensive review of vaccine therapy for glioblastoma. In addition, we identify the main biomarkers, including isocitrate dehydrogenase, epidermal growth factor receptor, and telomerase reverse transcriptase, known as potential immunotherapeutic targets in glioblastoma, as well as the current status of clinical trials. This paper also lists proposed solutions to overcome the obstacles facing immunotherapy in glioblastomas.

Visceral leishmaniasis as a rare cause of granulomatous hepatitis.

Visceral leishmaniasis (VL) is a potentially fatal infection caused by species of Leishmania. It is characterized by fever, weight loss, anemia, and enlargement of the spleen and liver. Hepatitis due to VL is one of the causes of granulomatous hepatitis rarely described in the literature. It poses a problem of differential diagnosis with other causes, notably infectious and autoimmune. Hence the need for a global clinical, biological, and histological evaluation to orientate this entity, especially in endemic countries like ours. In the present case study, a 2-year 8-month-old boy was diagnosed with VL and treated with meglumine antimoniate; the evolution was marked after 2 months by the persistence of a large liver; laboratory results showed elevated liver functions and anemia. A liver biopsy was performed, and the histological findings confirmed the diagnosis of granulomatous hepatitis.