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Sarcoidosis is a systemic disorder characterized by the development of granulomatous inflammation in various organs of the body. Hypercalcemia is one of its manifestations. We present a case of malignant hypercalcemia in a 77-year-old man, diagnosed as sarcoidosis following multiple assessments and histological confirmation showing noncaseating granulomas. In the absence of an etiological diagnosis, treatment was initially based on hydration, diuretics, and bisphosphonate. Glucocorticoid therapy can be the standard treatment for hypercalcemia related to sarcoidosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Lakhal et al.)

Sarcomatoid carcinoma (SC) is a rare primary malignant tumor belonging to the group of non-small cell lung cancer (NSCLC). The diagnosis requires proper tumor sampling to exclude sarcoma, which is the main differential diagnosis. However, the prognosis of these tumors is poor, with a median survival rate lower than other NSCLC cases, mainly due to their aggressiveness and resistance to chemotherapy, especially platinum salts. In this report, we discuss a case of a 62-year-old male patient who presented at admission with hemoptysis and dyspnea. The diagnosis process involved thoracic computed tomography (CT) and fiberoptic bronchoscopy, which revealed tissue thickening at the carina and a mass extending from the lower end of the trachea to the carina, which was confirmed by biopsy. Unfortunately, despite receiving neoadjuvant radiotherapy and having endotracheal prosthesis, the patient succumbed to tumor progression. Our case highlights the aggressive nature of this tumor and underscores the importance of early detection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Charii et al.)

The diagnosis of chronic lymphoid leukemia (CLL) is essentially based on a blood smear and immunophenotyping by flow cytometry of circulating lymphocytes. Unusual locations of the disease can sometimes be observed. Here we report the case of a patient admitted for the management of pleurisy. The pleural effusion was lymphocytic exudate; histological examination of the pleural biopsy along with immunohistochemistry helped yield the diagnosis of secondary localization of CLL. The patient was transferred to the Internal Medicine department where chemotherapy was introduced., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Thouil et al.)

Background: Coronavirus Disease 2019 (COVID-19) is a viral pandemic disease that may induce severe pneumonia in humans. In this paper, we investigated the putative implication of 12 vaccines, including BCG, OPV and MMR in the protection against COVID-19. Sequences of the main antigenic proteins in the investigated vaccines and SARS-CoV-2 proteins were compared to identify similar patterns. The immunogenic effect of identified segments was, then, assessed using a combination of structural and antigenicity prediction tools., Results: A total of 14 highly similar segments were identified in the investigated vaccines. Structural and antigenicity prediction analysis showed that, among the identified patterns, three segments in Hepatitis B, Tetanus, and Measles proteins presented antigenic properties that can induce putative protective effect against COVID-19., Conclusions: Our results suggest a possible protective effect of HBV, Tetanus and Measles vaccines against COVID-19, which may explain the variation of the disease severity among regions.

Background: Since the 1990s, the epidemiology of bacterial meningitis worldwide has changed thanks to vaccination. In Tunisia, the main causative pathogens were Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae serotype b (Hib). Only Hib vaccination was available during our study period., Objectives: We performed a laboratory case report based-study of suspected bacterial meningitis in Northern Tunisia from January 2014 to June 2017., Methods: CSF samples obtained from children beyond neonatal age with suspicion of meningitis were tested by two real time PCRs, targeting pneumococcus, meningococcus and Hib, and conventional methods., Results: Using real-time PCR, 63 were positive including ten supplementary cases compared to conventional methods. A general decrease of bacterial meningitis cases was demonstrated comparing to previous data. Pneumococcus was predominant (69.84%) followed by meningococcus (28.57%) and Hib (1.59%). The main serotypes were 14, 19F, 6B and 23F for pneumococcus and serogroup B for meningococcus . Most cases occurred during cold season and children under one year were the most affected by bacterial meningitis., Conclusion: Our study suggests the predominance of pneumococcal cases. It may provide valuable data on meningitis epidemiology before the introduction of pneumococcal vaccine, which may be useful for future evaluation., (© 2020 Haddad-Boubaker S et al.)

Introduction: Bacterial meningitis is a medical emergency requiring a fast and reliable diagnosis. Molecular methods such as real-time PCR (rt-PCR) offer an attractive alternative. Thus, this study aims to establish multiplex rt-PCRs detecting N. meningitidis, S. pneumoniae and H. influenzae b from cerebrospinal fluid in Tunisian children beyond neonatal age., Methodology: Using bioinformatic tools and experimentation, we validated the specificity and optimal criteria of PCRs for primers and probes of plyA (S. pneumoniae), ctrA and sodC (N. meningitidis) and bexA genes (H. influenzae b). We performed one multiplex RT-PCR for detection of S. pneumoniae and N. meningitidis targeting plyA and ctrA, sodC genes respectively, simultaneously with a singleplex RT-PCR for H. influenzae b. The sensitivity and specificity of our methods were assessed. Then, we tested our methods for 122 CSF samples collected from suspected meningitis cases between 2014 and 2016 in Bechir Hamza Children's Hospital of Tunis., Results: Our results have shown the sensitivity of the designed PCRs was up to 10-4 DNA dilution and the specificity was 100%. PCR evaluation has shown 51 positive samples: 38 of pneumococcal cases, 12 meningococcal cases, 1 case of H. influenzae b with 8.57% and 50% of supplementary positive cases rates respectively., Conclusions: Our assay proved to be very sensitive, specific and rapid for bacterial meningitis diagnosis. In the recent context of Hib vaccination, the possibility of detecting S. pneumoniae and N. meningitidis separately constitute an attractive opportunity. Nevertheless, simultaneous detection of Hib remains relevant in specific clinical context and for epidemiologic study., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2018 Sondes Haddad-Boubaker, Marwa Lakhal, Cyrine Fathallah, Aida Bouafsoun, Maher Kharrat, Amel Kechrid, Hanen Smaoui.)

Objectives: This work is aimed on the study of doxorubicin cardiotoxicity and hepatotoxicity in rats and the evaluation of protective effect of trimetazidine administrated concomitantly with doxorubicin for 3 days., Materials and Methods: Male Wistar rats used were subjected to different types of treatment (3 days); A: Control, B: Doxorubicin treatment and C: Trimetazidine and doxorubicin treatment. After sacrifice, tissular distribution of doxorubicin, cardiac scintigraphy, histological examination of the myocardium, and evaluation of liver function were assessed., Results: Obtained results show that doxorubicin has a high affinity to tissues especially the heart. It causes hepatotoxicity and cardiotoxicity marked by a significant increase of aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) levels and drop of the left ventricular ejection fraction (EF LV ) by scintigraphy. Histological examination showed general alteration of myocardium structure. Concomitant administration of trimetazidine attenuates significantly the cardiotoxicity and hepatotoxity induced by doxorubicin., Conclusion: We have evaluated the protective effect of trimetazidine on an animal model of doxorubicin-induced cardiotoxicity and hepatotoxicity. The evaluation of these effects were assessed by several means; tissular distribution of doxorubicin, histological examination, assessment of liver function, and EF LV by scintigraphy that characterizes the originality of this study.

Objectives: The primary aim of this study was to establish the population pharmacokinetic (PPK) model of bupivacaine after combined lumbar plexus and sciatic nerve blocks and secondary aim is to assess the effect of patient's characteristics including age, body weight and sex on pharmacokinetic parameters., Materials and Methods: A total of 31 patients scheduled for elective lower extremity surgery with combined lumbar and sciatic nerve block using plain bupivacaine 0.5% were included. The total bupivacaine plasma concentrations were measured before injection and after two blocks placement and at selected time points. Monitoring of bupivacaine was made by high performance liquid chromatography (HPLC) with ultraviolet detection. Non-linear mixed effects modeling was used to analyze the PPK of bupivacaine., Results: One compartment model with first order absorption, two input compartments and a central elimination was selected. The Shapiro-Wilks test of normality for normalized prediction distribution errors for this model (P = 0.156) showed this as a valid model. The selected model predicts a population clearance of 930 ml/min (residual standard error [RSE] = 15.48%, IC 95% = 930 ± 282.24) with inter individual variability of 75.29%. The central volume of distribution was 134 l (RSE = 12.76%, IC = 134 ± 33.51 L) with inter individual variability of 63.40%. The absorption of bupivacaine in two sites Ka1 and Ka2 were 0.00462/min for the lumbar site and 0.292/min for the sciatic site. Age, body weight and sex have no effect on the bupivacaine pharmacokinetics in this studied population., Conclusion: The developed model helps us to assess the systemic absorption of bupivacaine at two injections sites.

The disseminated BCG infection is a rare and serious complication of bacillus Calmette-Guerin (BCG) vaccine. We report a case of probable disseminated BCG infection in a 10-month-old child who had been vaccinated by BCG vaccine at birth. No incident was noted on the first days of vaccination. At the age of 40 days, she developed left supra clavicular and axillar abcessed lymph nodes. She was treated by surgical flattening of the lymph adenopathy. The same lymph node recurred at the age of 6 months and was treated with surgery. Few weeks after the second episode, cutaneous ulcerative lesions appeared. Cutaneous biopsy was performed and showed lesions compatible with tuberculosis. X-rays showed osteolysis of P1 of the middle finger in the left hand. She was treated by anti-tuberculosis antibiotics.

Measurements of Cyclosporine (CsA) systemic exposure permit its dose adjustment in allogenic stem cell transplantation recipients to prevent graft-versus-host disease. CsA LSSs were developed and validated from 60 ASCT patients via multiple linear regressions. All whole-blood samples were analyzed by fluorescence polarization immunoassay (FPIA-Axym). The 10 models that have used CsA concentrations at a single time point did not have a good fit with AUC(0-12) (R(2) < 0.90). C(2) and C(4) were the time points that correlated best with AUC(0-12 h), R(2) were respectively 0.848, and 0.897. The LSS equation with the best predictive performance (bias, precision and number of samples) utilized three sampling concentrations was AUC(0-12 h) = 0.607 + 1.569 × C(0.5) + 2.098 × C(2) + 3.603 × C(4) (R(2) = 0.943). Optimal LSSs equations which limited to those utilizing three timed concentrations taken within 4 hours post-dose developed from ASCT recipient's patients yielded a low bias <5% ranged from 1.27% to 2.68% and good precision <15% ranged from 9.60% and 11.02%. We propose an LSS model with equation AUC(0-12 h) = 0.82 + 2.766 × C(2) + 3.409 × C(4) for a practical reason. Bias and precision for this model are respectively 2.68% and 11.02%.

Purpose: In this study, we developed an ex vivo functional assay to assess liver metabolic capacity adapted from the lidocaïne test in rats., Methods: Animals used were subjected to different models of liver injury: hypothermic ischemia (H/I, n = 8), ischemia-reperfusion (I/R, n = 8) and CCl4 induced liver cirrhosis (n = 11), and compared with sham operated rats (n = 5). Livers were then extracted and a fragment of whole tissue was incubated with lidocaïne for 15, 30, 60, 120, 240, 360, and 720 min at which both lidocaïne and its major metabolite monoethylglycinexylidide (MEGX) were measured by high performance liquid chromatography (HPLC). A histological study and biochemical assays (transaminase levels) were also performed to further evaluate and confirm our data., Results: Pharmacokinetic profile of lidocaïne metabolism in sham-operated animals revealed that the maximum concentration of MEGX is achieved at 120 min. Both lidocaïne metabolism and MEGX formation levels were significantly altered in all three models of hepatic injury. The extent of hepatic damage was confirmed by increased levels of transaminase levels and alteration of hepatocyte's structure with areas of necrosis., Conclusion: Our method provides reliable and reproducible results using only a small portion of liver which allows for a fast and easy assessment of liver metabolic capacity. Moreover, our method presents an alternative to the in vivo technique and seems more feasible in a clinical setting.

Persistence of T cells engineered with chimeric antigen receptors (CARs) has been a major barrier to use of these cells for molecularly targeted adoptive immunotherapy. To address this issue, we created a series of CARs that contain the T cell receptor-zeta (TCR-zeta) signal transduction domain with the CD28 and/or CD137 (4-1BB) intracellular domains in tandem. After short-term expansion, primary human T cells were subjected to lentiviral gene transfer, resulting in large numbers of cells with >85% CAR expression. In an immunodeficient mouse xenograft model of primary human pre-B-cell acute lymphoblastic leukemia, human T cells expressing anti-CD19 CARs containing CD137 exhibited the greatest antileukemic efficacy and prolonged (>6 months) survival in vivo, and were significantly more effective than cells expressing CARs containing TCR-zeta alone or CD28-zeta signaling receptors. We uncovered a previously unrecognized, antigen-independent effect of CARs expressing the CD137 cytoplasmic domain that likely contributes to the enhanced antileukemic efficacy and survival in tumor bearing mice. Furthermore, our studies revealed significant discrepancies between in vitro and in vivo surrogate measures of CAR efficacy. Together these results suggest that incorporation of the CD137 signaling domain in CARs should improve the persistence of CARs in the hematologic malignancies and hence maximize their antitumor activity.

Mesothelin is a cell-surface molecule over-expressed on a large fraction of carcinomas, and thus is an attractive target of immunotherapy. A molecularly targeted therapy for these cancers was created by engineering T cells to express a chimeric receptor with high affinity for human mesothelin. Lentiviral vectors were used to express a single-chain variable fragment that binds mesothelin and that is fused to signaling domains derived from T-cell receptor zeta, CD28, and CD137 (4-1BB). When stimulated by mesothelin, lentivirally transduced T cells were induced to proliferate, express the antiapoptotic gene Bcl-X(L), and secrete multiple cytokines, all features characteristic of central memory T cells. When transferred intratumorally or intravenously into NOD/scid/IL2rgamma(-/-) mice engrafted with large pre-established tumors, the engineered T cells reduced the tumor burden, and in some cases resulted in complete eradication of the tumors at low effector-to-target ratios. Incorporation of the CD137 signaling domain specifically reprogrammed cells for multifunctional cytokine secretion and enhanced persistence of T cells. These findings have important implications for adoptive immunotherapy of cancer, especially in the context of poorly immunogenic tumors. Genetically redirected T cells have promise of targeting T lymphocytes to tumor antigens, confer resistance to the tumor microenvironment, and providing immunosurveillance.