Characterization of regulatory T cells in SARS-CoV-2 infected hemodialysis patients: relation to clinical and radiological severity.

BACKGROUND: Disordered Treg counts and function have been observed in patients with SARS-Cov-2 and are thought to contribute to disease severity. In hemodialysis patients, scarce data are available on the Treg response to SARS-CoV-2 or its relation to the clinical presentation. METHODS: A cross-sectional study included one hundred patients divided into three groups, thirty SARS-CoV-2-infected hemodialysis patients (COV-HD), and thirty confirmed SARSCoV-2 infected patients (COV), and forty non-infected hemodialysis patients (HD). Flow cytometric analysis of CD4, CD25, FoxP3, and CD39+ Tregs was done for all patients and tested for correlation to in-hospital mortality, clinical, radiological severity indices. RESULTS: COV-HD and COV patients had significantly lower Treg cell count than HD patients (Median value of 0.016 cell/ µl vs 0.28 cell/ µl, respectively- P: 0.001). COV-HD patients had higher CD39+ Tregs (median value of 0.006 cell/ µl vs 0.002 cell/ µl, respectively- P: 0.04). COV-HD patients had significantly lower hospital stay (median value of 3 vs 13 days, P:0.001), ICU admission rates (26.5% vs 46.7%, P:0.005) and in-hospital mortality (20.7% versus 43.3%, P:0.003) than COV patients. Treg and CD39 expressing Treg counts were not correlated to severity indices in both groups. A high neutrophil to lymphocyte ratio is strongly correlated to disease severity in COV-HD patients. CONCLUSIONS: This study provides evidence of T-cell, particularly T-regulatory cell decline in SARS-CoV-2 and suggests that hemodialysis per se does not distinctively impact the T-cell response. COV-HD patients exhibited a higher CD39+ Treg count and a better clinical profile, however, larger studies are needed to extrapolate on these findings.

Cancer incidence in the Tobruk area, eastern Libya: first results from Tobruk Medical Centre.

OBJECTIVES: Cancer is a major cause of morbidity and mortality worldwide, and it is an increasing problem in developing countries. Estimation of the incidence of cancer is important, especially in regions with limited epidemiological data on cancer. Therefore, the aim of this study was to provide an updated report on the incidence of cancers in the Tobruk region in eastern Libya. METHODS: Data on cancer patients from the records of the Department of Histopathology of Tobruk Medical Centre from January 2013 to June 2020 were included. RESULTS: In total, 402 cases were recorded. Men patients accounted for 30.3% (n=122) of cases, and women patients represented 69.6% (n=280). The overall mean age at the time of the first diagnosis was 49.0±17.1 years. The most common malignancies were breast and uterine cancer in women (18.4%, n=74; 15.9%, n=64, respectively), colorectal cancer (11.6%, n=47; 26 in women and 21 in men), bladder cancer (8.2%, n=33; 8 in women and 25 in men), and thyroid cancer (8.0%, n=32; 23 in women and 9 in men). CONCLUSIONS: Breast and uterine cancers were the most common cancers in women, and bladder and colorectal cancer were the most common cancers in men, followed by colorectal cancer in both genders. These data will help health authorities launch preventive plans for cancer in the region. Further studies to identify aetiological factors and cancer-related risk factors need to be conducted in the region.

MPL Y252H anMd PL F126fs mutations in essential thrombocythemia: Case series and review of literature.

Essential thrombocythemia (ET) is a clonal bone marrow disease, characterized by increased production of platelets along with other clinical and bone marrow findings. Most patients with ET will have a somatic mutation in one of the known gene locations of JAK2, CALR, or MPL that can upregulate the JAK-STAT pathway. MPL mutation is present in 5% of cases with the most common mutations being W515L and W515K. In this report we describe 2 cases of patients with clinical and laboratory picture of ET. One patient carried MPLY252H mutation which is previously unreported in the adult population but has been shown to be a gain-of-function mutation. The other patient carried MPL F126fs mutation which is not known to be of clinical importance and has not been previously reported.

Verrucous carcinoma arising in a long standing Buschke-Löwenstein tumor.

Giant condyloma acuminatum is a rare variant of genital warts also known as Buschke-Löwenstein tumor. It is characterized by a slow progression of exophytic, ulcerative, and cauliflower-shaped tumor with benign histological features. Verrucous carcinoma however is a rare variant of well-differentiated squamous cell carcinoma with limited metastatic potential.

Extraskeletal Chondrosarcoma: Long-term Follow-up of a Patient with Metastatic Disease.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma with an indolent course and poor response to systemic treatment. We present a case of a 53-year-old male who presented with right gluteal extraskeletal myxoid chondrosarcoma. He was treated with wide local excision after receiving 50 Gray of neoadjuvant radiation therapy. Three years later he was found to have a left lower lobe lung nodule that was slowly increasing in size. He underwent a left lower lobectomy and the nodule was confirmed to be consistent with the patient's history of EMC. One year later, lung imaging showed multiple small nodules bilaterally consistent with metastatic disease. The patient opted for watchful waiting approach. Routine follow-up imaging for four years shows a very slow progression of his disease burden. He continues to be asymptomatic. This case demonstrates the natural course of EMC and argues in favor of the watchful waiting approach in treating this disease.

Clinical Applications of Regulatory T cells in Adoptive Cell Therapies.

Interest in adoptive T-cell therapies has been ignited by the recent clinical success of genetically-modified T cells in the cancer immunotherapy space. In addition to immune targeting for malignancies, this approach is now being explored for the establishment of immune tolerance with regulatory T cells (Tregs). Herein, we will summarize the basic science and clinical results emanating from trials directed at inducing durable immune regulation through administration of Tregs. We will discuss some of the current challenges facing the field in terms of maximizing cell purity, stability and expansion capacity, while also achieving feasibility and GMP production. Indeed, recent advances in methodologies for Treg isolation, expansion, and optimal source materials represent important strides toward these considerations. Finally, we will review the emerging genetic and biomaterial-based approaches on the horizon for directing Treg specificity to augment tissue-targeting and regenerative medicine.

Adequate Neutrophil Responses and Non-Inferior Clinical Outcomes Can Be Achieved by a Two-Day Course of Low-Dose Filgrastim: A Retrospective Single Institution Experience.

Background Filgrastim is used in the setting of chemotherapy-induced neutropenia to stimulate recovery of bone marrow, which allows for further chemotherapy administration without delay. The recommended dose is 5 ug/kg. The commercially available vials of the drug come in two strengths; 300 ug and 480 ug. Due to these limitations in dosage formulations, it is a frequent occurrence to administer a lower dosage to patients weighing more than 60 kg, in whom the ideal dose would have been more than 300 ug but less than 480 ug. It is also a frequent practice to administer the drug for two consecutive days as it often leads to adequate response that will render patients eligible for their next cycle administration. Objective To determine whether a course of 300 ug of filgrastim administered daily for two consecutive days was as successful at reducing chemotherapy-induced neutropenia-related complications in patients with a higher weight (>60 kg) and hence receiving suboptimal dose as compared to those with weight less than 60 kg who are receiving the recommended dose. Methods We identified 91 patients from our facility with chemotherapy-induced neutropenia treated with 300 ug of filgrastim daily for two consecutive days, and we separated them into low, medium, and high weight groups. Multivariate logistic regression models examined correlations between outcomes (e.g., increases in absolute neutrophil count) and predictors (e.g., weight groups). Results The vast majority of encounters demonstrated rises in white blood cell (WBC) and absolute neutrophil count (ANC). Infection rates were not significantly different between low and medium weight groups (5% vs 0%; p = 0.1658), but the high weight group's infection rate was significantly higher than the medium weight group (5% vs 33%; p = 0.001). The high weight group did have an increased rate of febrile neutropenia as compared to medium and low weight groups, but these differences were not significant. Incidences of chemotherapy delay and dose reduction were comparable across the three weight groups. Limitations Retrospective study, small sample size, heterogeneous cancer sites and different chemotherapy regimens administered limit generalizability of findings. Conclusion Patients with weights <85 kg receiving a two-day course of 300 ug of filgrastim have similar neutropenia-related complication rates with a potential percent cost-savings of roughly 43%.