Evaluation of the antiviral activity of new dermaseptin analogs against Zika virus.

Zika virus represents the primary cause of infection during pregnancy and can lead to various neurological disorders such as microcephaly and Guillain-Barré syndrome affecting both children and adults. This infection is also associated with urological and nephrological problems. So far, evidence of mosquito-borne Zika virus infection has been reported in a total of 89 countries and territories. However, surveillance efforts primarily concentrate on outbreaks that this virus can cause, yet the measures implemented are typically limited. Currently, there are no specific treatments or vaccines designed for the prevention or treatment of Zika virus infection or its associated disease. The development of effective therapeutic agents presents an urgent need. Importantly, an alternative for advancing the discovery of new molecules could be dermaseptins, a family of antimicrobial peptides known for their potential antiviral properties. In this study, we carried out the synthesis of dermaseptins and their analogs and subsequently assessed the bioactivity tests against Zika virus (ZIKV PF13) of dermaseptins B2 and S4 and their derivatives. The cytotoxicity of these peptides was investigated on HMC3 cell line and HeLa cells by CellTiter-Glo® Luminescent Cell Viability Assay. Thereafter, we evaluated the antiviral activity caused by the action of our dermaseptins on the viral envelope using the Fluorescence Activated Cell Sorting (FACS). The cytotoxicity of our molecules was concentration-dependent at microgram concentrations Expect for dermaseptin B2 and its derivative which present no toxicity against HeLa and HMC3 cell lines. It was observed that all tested analogs from S4 family exhibited antiviral activity with low concentrations ranging from 3 to 12.5 µg/ml , unlike the native B2 and its derivative which increased the infectivity. Pre-incubating of dermaseptins with ZIKV PF13 before infection revealed that these derivatives inhibit the initial stages of virus infection. In summary, these results suggest that dermaseptins could serve as novel lead structures for the development of potent antiviral agents against Zika virus infections.

Fournier's gangrene revealing an acute arterial occlusion: A case report.

INTRODUCTION AND IMPORTANCE: Fournier gangrene (FG) is a rare form of necrotizing fasciitis that affects both the deep and superficial layers of the perineal genital region. When left untreated, Fournier gangrene can rapidly advance, leading to substantial morbidity and mortality. Herein, we present a case of Fournier's gangrene, which revealed acute arterial occlusion. To the best of our knowledge, few cases of Fournier's gangrene secondary to arterial occlusion have been reported. CASE PRESENTATION: We report the case of a 37-year-old man with no known medical history who presented with fever and painful swelling of the scrotum. Physical examination revealed a large black spot on the scrotum surrounded by erythema, suggestive of Fournier's gangrene. We performed an extended debridement of the scrotal area. Three days later, the patient complained of severe pain in the left foot accompanied by numbness. Lower limb computed tomographic angiography (CTA) revealed multiple arterial occlusions. Thrombectomy and anticoagulation therapy were crucial in managing the vascular thrombosis and preventing the further extension of the gangrene. CLINICAL DISCUSSION: This case underscores the importance of recognizing diverse etiologies of Fournier's gangrene, including vascular involvement, and emphasizes the need for a multidisciplinary approach. Early identification, aggressive surgical debridement, and broad-spectrum antibiotics remain the cornerstone of management, with the added consideration of anticoagulation in cases involving vascular thrombosis. CONCLUSION: FG is a rare yet potentially life-threatening condition. Its multifaceted etiologies, including vascular factors, underscore the complexity of its presentation and challenges for timely diagnosis. The recognition of vascular involvement as a potential etiology of FG warrants further in-depth exploration.

Recurrent paratesticular liposarcoma: a case report.

Introduction and importance: Paratesticular liposarcoma (PTL) is a rare condition, with fewer than 200 cases reported worldwide. It is a malignant tumor that originates from fat tissue with high risk of recurrence. Herein, the authors present a contralateral recurrence of a treated PTL. To the best of the authors' knowledge, in the current literature, there are few cases reported with recurrent PTL. Case presentation: The authors report the case of a 62-year-old man who presented with a rapidly growing painless right hemiscrotal swelling. Clinical and radiographic evidence suggested the presence of two paratesticular tumors. The patient underwent a radical orchidectomy with resection of the two tumors through an inguinal approach. The histologic examination revealed a sclerosing, well-differentiated liposarcoma. The decision of the multidisciplinary consultation meeting was not to do adjuvant treatment. A follow-up of 12 months showed recurrence of the contralateral scrotum revealed by an FDG-PET/scan. Clinical discussion: PTL, a rare spermatic cord tumor, affects adults aged 50-60, often presenting with scrotal swelling. Diagnosis involves ultrasound, computed tomography, and magnetic resonance imaging. Surgical intervention, including radical orchiectomy and adjuvant radiotherapy, is common for management, while the role of chemotherapy is inconclusive. High-grade subtypes carry a higher recurrence risk. Conclusion: PTL is often misdiagnosed preoperatively. It is typically managed through radical orchidectomy, which includes wide excision and high ligation to ensure free surgical margins and avoid recurrence. The role of adjuvant therapy remains debatable. Despite a generally favorable prognosis, long-term follow-up is crucial because of the elevated risk of recurrence.

Chronic-phase chronic myeloid leukemia: Incidence of BCR/ABL transcript and its correlation with presenting features, response to treatment, and survival.

Introduction: Chronic myeloid leukemia (CML) is characterized by Philadelphia chromosome resulting in the fusion between the BCR gene, located on chromosome 22, and the ABL gene on chromosome 9. The prognostic significance of BCR-ABL transcript variants in CML is controversial. The aim of the current study was to evaluate the clinico-hematological presentation and evolution of the disease, response to treatment and survival according to transcript type in chronic phase CML patients. Results: The median age of our population was 50 years with a slight female predominance (sex-ratio 0.78). Sixty percent had the b3a2 transcript and 34% had the b2a2 type. Patients with the co-expression of these two transcripts (4.5%) and those with e19a2 were excluded from the analysis. Patients with b3a2 subtype were associated significantly with thrombocytosis (p = 0.006) and higher Sokal score (p = 0.038) compared to those with b2a2 transcript. The two isolated transcripts were not significantly associated with gender, age group, blast cell percentage or the identified ranges of spleen size. Complete cytogenetic response at 12 months for b3a2 patients and b2a2 patients was 78.6% and 21.4% respectively. This difference was statistically significant (p = 0.001, HR = 9.5, 95% CI 6.5-13.7). Patients with b3a2 transcript had a higher rate of optimal molecular response at 3 months (p = 0.04, HR = 4.2, 95% CI 1-17.3) and major molecular response at 12 months (p = 0.004, HR = 4.9, 95%CI 1.5-15.1). At the date of last follow-up, most patients achieving deep molecular response (MR4 or deeper) belonged to b3a2 group (79%) (p = 0.003, HR = 5.2, 95% CI 1.6-16.4). We did not find a significant difference in OS and EFS between the two groups. Conclusion: Our study concluded that b2a2 transcript is a prognostic factor in cytogenetic and molecular response but further studies are needed to complete this aspect.

Left paratesticular fibrous pseudotumor on the single testis and contribution of imaging in therapeutic management, a case report.

INTRODUCTION AND IMPORTANCE: Paratesticular fibrous pseudotumor is a rare benign tumor. Clinically, it can mimic testicular malignancy, but this lesion results from a reactive proliferation of inflammatory and fibrous tissue. CASE PRESENTATION: A 62-year-old man presented with left scrotal swelling dating back years. A left paratesticular mass is palpated, firm and painless. Ultrasound showed a heterogeneous and hypoechoic lesion in a single left testicle; the right testicle was not found in the scrotum or at the inguinal level. CT scan showed a hypodense left scrotal mass. The scrotal MRI showed the presence of a paraliquid left intrascrotal formation pushing back the left testicle. We performed a scrotal exploration with excision of the paratesticular mass, sparing the left testicle. The definitive pathological diagnosis was reported as paratesticular fibrous pseudotumor. CLINICAL DISCUSSION: Paratesticular Fibrous pseudotumors are a rare tumor with approximately 200 cases reported to date. These lesions constitute 6 % of all paratesticular lesions. Magnetic resonance imaging can give additional information when an ultrasound is inconclusive. The treatment of choice is a scrotal exploration of the mass and frozen section biopsy to avoid unnecessary orchiectomy. CONCLUSION: The diagnosis of paratesticular Fibrous pseudotumor is challenging. The contribution of scrotal MRI and intra-operative frozen section is essential for therapeutic management.

Plasmacytoid bladder cancer: a rare case report.

Plasmacytoid carcinoma of the bladder is a rare histological variant of urothelial carcinoma associated with late presentation. This pattern of disease may portend an extremely poor prognosis and significant challenges for treatment with curative intent. Case presentation: The authors report a case of a patient with locally advanced plasmacytoid urothelial carcinoma (PUC) of the bladder. A 71-year-old man with a history of chronic obstructive pulmonary disease presented with gross hematuria. The rectal examination revealed a fixed bladder base. A computed tomography scan showed a pedunculated lesion arising from the anterior and left lateral bladder wall and extended to the perivesical fat. The patient underwent transurethral resection of the tumor. The histologic examination revealed the presence of muscle-invasive PUC of the bladder. The decision of the multidisciplinary consultation meeting was to do palliative chemotherapy. Thus, the patient could not receive systemic chemotherapy and died 6 weeks after transurethral resection of the bladder tumor. Clinical discussion: A plasmacytoid variant of urothelial carcinoma is a rare subtype of urothelial carcinoma that has a poor prognosis with a high mortality rate. The disease is usually diagnosed at an advanced stage. Given the rarity of plasmacytoid bladder cancer, treatment guidelines are not clear; therefore, more aggressive treatment may be required. Conclusion: PUC of the bladder is characterized by high aggressiveness, an advanced stage at the time of diagnosis, and a poor prognosis.

Primary extragastrointestinal stromal tumor of the prostate: review of the literature and case report.

The extragastrointestinal stromal tumor (EGIST) is defined as a mesenchymal neoplasm arising from soft tissues outside the gastrointestinal tract, and the prostate is a rare presentation site. Case presentation: A 58-year-old man was presented with lower urinary tract symptoms for 6 months. A digital rectal examination revealed a markedly enlarged prostate with a smooth, bulging surface. Prostate-specific antigen density was 0.5 ng/ml. MRI of the prostate showed an enlarged prostatic mass with hemorrhagic necrosis. Transrectal ultrasound-guided prostate biopsy was performed and pathological reports suggested a gastrointestinal stromal tumor. The patient refused radical prostatectomy and received only imatinib treatment. Clinical discussion: The diagnosis of EGIST of the prostate is extremely rare and depends on the histopathologic features with immunohistochemical results. The treatment is essentially based on radical prostatectomy, but there are other therapeutic modalities associating surgery with adjuvant or neoadjuvant chemotherapy. For patients refusing surgery, treatment with imatinib alone appears to be a therapeutic solution. Conclusion: Despite the rarity, EGIST of the prostate should be included in the differential diagnosis of patients presenting with lower urinary tract symptoms. There is no consensus regarding the treatment of EGIST, and the patients are treated as per the risk stratification.

Comprehensive analysis of BCR/ABL variants in chronic myeloid leukemia patients using multiplex RT-PCR.

BACKGROUND: A specific chromosomal abnormality, the Philadelphia chromosome (Ph), is present in 90 - 95% of patients with chronic myeloid leukemia (CML). This aberration results from a reciprocal translocation between chromosomes 9 and 22, creating a BCR/ABL fusion gene. The diagnosis of CML is based on the detection of BCR/ABL gene or Ph chromosome. Fusion proteins with different sizes are encoded depending on the breakpoint in the BCR gene. In general, 3 breakpoint cluster regions in the BCR gene have been described: major (M-bcr), minor (m-bcr), and micro (micro-bcr). The aim of this study was to search the BCR/ABL fusion gene in 60 Tunisian patients using multiplex reverse transcription polymerase chain reaction (RT-PCR) and compare our results with those of conventional cytogenetics. METHODS: Bone marrow (BM) or peripheral blood (PB) samples, obtained at diagnosis, from 60 patients were analyzed by multiplex RT-PCR and conventional cytogenetics. RESULTS: 45 patients examined were positive for some type of BCR/ABL rearrangement. The majority of the patients (97.77%) expressed one of the p210 BCR-ABL transcripts (63% with b3a2 and 36% with b2a2) while only one patient showed a rare e19a2 transcript. CONCLUSIONS: Multiplex RT-PCR is a fast and reliable technique for improved detection of typical and atypical BCR/ABL transcripts.

Analysis of the clinico-hematological relevance of the breakpoint location within M-BCR in chronic myeloid leukemia.

The Philadelphia chromosome (Ph) derives from the balanced translocation between chromosomes 9 and 22. This chromosomal translocation results in the fusion between the 5' part of the BCR gene, normally located on chromosome 22, and the 3' part of the ABL gene on chromosome 9 giving origin to a BCR-ABL fusion gene which is transcribed and then translated into a hybrid protein. In general, three breakpoint cluster regions in the BCR gene have been described: major (M-BCR), minor (m-BCR) and micro (µ-BCR). Three main variants of the BCR-ABL gene have been described depending on the length of the sequence of the BCR gene included that encode for the P190, P210, P230 proteins. Most patients (95 %) were found to have P210 protein that resulted from rearrangement in the M-BCR region in the BCR gene and thus gives rise to b2a2 or b3a2 variants. The incidence of one or other rearrangement in chronic myeloid leukemia (CML) patients varies in different reported series. These two variants are associated with distinct clinical types of human leukemias. In this study, we report the frequencies of M-BCR-ABL fusion transcripts in 44 CML patients and we review the data on the correlations between the type of M-BCR/ABL variant and the corresponding sex, age and biological features. Forty-four untreated chronic phase CML patients were studied. The type of BCR-ABL fusion transcripts was determined by reverse transcriptase polymerase chain reaction (RT-PCR). More than half of them showed b3a2 fusion transcript (64 %), while (36 %) showed b2a2 transcript. No patients coexpressed b3a2/b2a2. Correlation between biological data demonstrated that: (a) M-BCR rearrangements were not associated with the sex of the patients. (b) Patients with b3a2 rearrangements were older than patients with b2a2 transcripts. (c) M-BCR rearrangements were influenced neither by the white blood count (WBC) nor with hemoglobin levels. However, platelet level is more elevated in patients with b3a2 transcript (681.2/L vs. 207/L; P = 0.001). In conclusion, we observed significant correlations between age, platelet level and M-BCR-ABL transcript, these observations deserve further investigations.

Translocation t(X;10)(p10;p10): a rare chromosomal abnormality in a new born female with acute myeloid leukemia.

Sex chromosomes are infrequently involved in patients with hematologic malignancies. In most instances, the abnormality is either duplication in the q arm or deletion and translocation involving the q13 and q24 regions. We report herein a rare translocation t(X;10)(p10;p10) in a newborn with 2 months and 20 days with acute myeloid leukemia (AML) (FAB, M4). Cytogenetic analysis detected a cell clone with t(X;10)(p10;p10). Thus was confirmed by FISH analysis with whole chromosome painting (WCP) specific for chromosomes X and 10. The patient was treated with chemotherapy, and a complete morphologic and cytogenetic remission was achieved. To our knowledge, our case is the first report of a neonatal AML4 with t(X; 10). The patient had an excellent early response to a salvage AML-type therapy. The prognostic significance of the t(X; 10) in this setting remains unclear. Due to the rarity of this translocation, further cytogenetic and molecular biologic studies are required to elucidate the clinical and molecular significance of this unusual karyotypic finding.

Molecular cytogenetic study of derivative chromosome 9 deletion in chronic myeloid leukemia patients.

The aims of this study are to investigate the frequency of derivative chromosome 9 (der (9)) deletion in Tunisian patients with chronic myeloid leukemia (CML) and to assess the correlation between this deletion and the cytogenetic response for patients treated with hydroxyurea (HU) or imatinib (IM). Karyotype analysis of 336 patients with CML was performed with R-banding technique. Fluorescence in situ hybridization (FISH) was carried using home-brew probes 17L7 and 248J22 for detecting, respectively, adjacent 5'ABL and 3'BCR deletions on der(9). Cytogenetic study demonstrated typical t(9;22)(q34;q11) translocation in 89.6% and variant translocation in 10.4% of patients. Interphase FISH studies showed deletion of der(9) in 59 (17.6%) of the 336 patients, 23 (39%) of them had variant rearrangements. There are 19 patients with solely 5'ABL deletion and 40 with concomitant 5'ABL and 3'BCR deletions. Cytogenetic response was evaluated during 18 months with HU or IM therapy. Our results demonstrate that (a) 3'BCR deletion is associated with 5'ABL deletion in all patients with der(9) deletions, (b) the 5'ABL and 3'BCR deletions arise simultaneously with t(9;22), (c) deletions on der(9) chromosome were frequently encountered in older patients and in patients presenting variant rearrangements, (d) both 5'ABL and 3'BCR deletions were associated with cytogenetic response failure in patients treated with HU, however, patients treated with IM and carrying der(9) deletions presented better cytogenetic response.