Prevalence of Epstein-Barr virus in Sjögren's syndrome in Tunisia

PURPOSE: The cause of Sj?gren's syndrome is unclear. Several studies suggested the role of Epstein-Barr virus (EBV) in the pathogenesis of this syndrome, but this always remains a subject of numerous controversies. The purpose of this study was to evaluate the prevalence of EBV in Sj?gren's syndrome in Tunisia. METHODS: A series of 31 paraffin-embedded biopsies of salivary glands from patients with Sj?gren's syndrome were studied in comparison with 19 control glands. EBV was investigated by PCR, EBERs in situ hybridization and by immunohistochemistry for the detection of LMP1, EBNA2 and ZEBRA. RESULTS: EBV DNA was detected by PCR in 3 of 22 PCR beta-globin positive Sj?gren's syndrome cases (13.6%) and in 2 of 17 PCR beta-globin positive control glands (11.7%); in situ hybridization positivity was noted in rare lymphocytes in the 3 EBV positive cases of Sj?gren's syndrome, but not in control glands; immunohistochemical study was negative in all cases. CONCLUSION: EBV infection does not appear to play a significant role in the pathogenesis of Sj?gren's syndrome in Tunisia.     

Prenatal diagnosis of ectopia cordis: case report

Ectopia cordis is a rare and impressive malformation presenting as an isolated lesion or as part of the Cantrell's pentology syndrom. It is defined as an anomaly in which the fetal heart lies outside the thoracic cavity. THE AIM of the study is to report the prenatal diagnostic features and management of ectopia cordis. CASE REPORT: We report a prenatal diagnosis case of ectopia cordis using two-dimensional ultrasound at 19 weeks of gestation. Multiple congenital anomalies were found. The most important one was the presence of a ventral thoracoabdominal wall defect with exstrophy of the heart, liver, stomach and intestines. Histopathological examination confirmed the ultrasound findings. Due to severity of the malformations, termination of pregnancy was made.     

Efficient induction of apoptosis by doxorubicin coupled to cell-penetrating peptides compared to unconjugated doxorubicin in the human breast cancer cell line MDA-MB 231

Doxorubicin (Dox) is a commonly used drug to treat various types of cancers. Previously, we demonstrated that coupling Dox to cell-penetrating peptides (CPPs) represent a valuable strategy to overcome drug resistance in MDA-MB 231 breast cancer cells. In the present study, we evaluated the properties of these Dox conjugates (Dox–CPPs) in terms of apoptosis induction. Dox–CPPs were found to induce apoptotic death in MDA-MB 231 cells at a lower dose than that needed for unconjugated Dox. Cell death induction was associated with Bax oligomerisation, release of cytochrome c, caspase activation, chromatin condensation and internucleosomal degradation. However, whereas Bcl-2 overexpression was very potent in inhibiting apoptosis triggered by Dox, this anti-apoptotic protein was largely inefficient in preventing Dox–CPPs-induced apoptosis. These observations suggest that mitochondrial disruption is the main event in Dox-induced apoptotic signaling but that Dox–CPPs are probably able to trigger additional apoptotic pathways independent of mitochondrial events. Thus, the higher efficacy of Dox conjugated to CCPs in apoptosis induction might not be due exclusively to increased drug accumulation but also to the activation of multiple apoptotic pathways.     

Emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis,therapeutics and vaccines

The emergence of novel and evolving variants of SARS-CoV-2 has fostered the need for change in the form of newer and more adaptive diagnostic methods for the detection of SARS-CoV-2 infections. On the other hand, developing rapid and sensitive diagnostic technologies is now more challenging due to emerging variants and varying symptoms exhibited among the infected individuals. In addition to this, vaccines remain the major mainstay of prevention and protection against infection. Novel vaccines and drugs are constantly being developed to unleash an immune response for the robust targeting of SARS-CoV-2 and its associated variants. In this review, we provide an updated perspective on the current challenges posed by the emergence of novel SARS-CoV-2 mutants/variants and the evolution of diagnostic techniques to enable their detection. In addition, we also discuss the development, formulation, working mechanisms, advantages, and drawbacks of some of the most used vaccines/therapeutic drugs and their subsequent immunological impact.

Key message

• The emergence of novel variants of the SARS-CoV-2 in the past couple of months, highlights one of the primary challenges in the diagnostics, treatment, as well as vaccine development against the virus.
• Advancements in SARS-CoV-2 detection include nucleic acid based, antigen and immuno- assay-based and antibody-based detection methodologies for efficient, robust, and quick testing; while advancements in COVID-19 preventive and therapeutic strategies include novel antiviral and immunomodulatory drugs and SARS-CoV-2 targeted vaccines.
• The varied COVID-19 vaccine platforms and the immune responses induced by each one of them as well as their ability to battle post-vaccination infections have all been discussed in this review.

     

Beneficial of adding Tocilizumab to standard care in critical forms of Covid-19 pneumonia: Study on paired series

Introduction: Tocilizumab (TCZ), a humanized monoclonal antibody directed against interleukin-6 (IL-6) receptors, has been tried in various studies as a Covid-19 therapy with controversial results. Aim: To evaluate the effectiveness of adding TCZ to standard care (SC) in critical Covid-19 patients. Methods: it was designed retrospectively as a comparative study on two paired series of critical patients affected with Covid-19: the 1^st group received TCZ plus SC versus a 2^nd group which received only SC. The matching criteria were age, sex and severity score and the matching was based on the propensity score matching (PSM) by the nearest neighbor. Outcomes were: survival, mechanical ventilation (MV) and nosocomial infections. Results: Ninety patients were included by pairing estimated successful (PSM > 0.5 in more than 50% in each group for all matching criteria). 55.5% of SC group progressed to stage 3-acute respiratory distress syndrome (ARDS) versus 31% of TCZ+SC patients (p=0.03). No effect of TCZ was found on mortality (49% in each group, p=1) nor on MV use (p=0.67). ICU stay was more prolonged in TCZ+SC group (16 versus 8 days, p <10^-3). The administration of TCZ induced a significant decrease in CRP but not changed the IL-6 dosage. Nosocomial infections occurred in 18 (40%) of TCZ+SC group comparatively to 15 (33,5%) of SC group, p=0.66. Conclusion: Tocilizumab reduced the risk of progression to severe ARDS probably due to its immune-modulating properties. But no beneficial effect was found on survival or on the use of ventilation.     

HPV infection and p16INK4A and TP53 expression in rare cancers of the uterine cervix

Cervix cancer remains among most commonly diagnosed cancer in developing countries. Except squamous cell carcinoma and adenocarcinoma, the etiopathology and oncogenic mechanisms of rare cancers remain largely unknown. The study was performed to investigate the value of HPV infection and the expression of p16^INK4A and TP53 in rare primitive cancers of the cervix.We conducted a retrospective study of rare primitive cancers of the cervix. Main clinicopathological features were reported. HPV infection was detected by in situ hybridization. Expression of p16^INK4A and TP53 was analyzed by immunohistochemistry.Overall, seven cases were identified, including basaloid squamous cell carcinoma (BSCC, n?=?2), small cell neuroendocrine carcinoma (SCNEC), granulocytic sarcoma without acute myeloid leukemia, leiomyosarcoma, primitive neuroectodermal tumor and botryoid-type embryonic rhabdomyosarcoma. The mean age of patients was 53.7 years. Four cancers were diagnosed at advanced stages. The prognosis was unfavorable and associated with patient death in five cases. HPV types 16/18 were detected in BSCCs and SCNEC. Strong and diffuse p16^INK4A overexpression was described in the nucleus and the cytoplasm of all tumor cells of BSCCs and SCNEC. The remaining cancers exhibited only scattered and focal p16^INK4A staining. Mutated TP53 protein was detected in BSCC (case 1) and GS.Rare cancers of the cervix are aggressive and associated with poor prognosis. In contrast to mesenchymal tumors, BSCCs and SCNEC are etiologically related to high-risk HPV infection and could be identified by block positive p16^INK4A overexpression as common cancers of the cervix. TP53 mutations are not a negligible genetic event in rare cervical cancers.     

Human subconjunctival dirofilariasis: two Tunisian case studies

Two new cases of human subconjunctival dirofilariasis are reported in Tunisia. Dirofilaria immitis was identified in the first case and Dirofilaria repens in the second. Diagnosis was made by histological examination of excised nodules. We note that the patients are young (8 and 10 years, respectively) and that cases of human dirofilariasis caused by Dirofilaria immitis are present in Tunisia.