MDSC expansion during HIV infection: regulators, ART and immune reconstitution.

Myeloid-derived suppressor cells (MDSCs) become expanded in different pathological conditions including human immunodeficiency virus (HIV) infection and this may worsen the disease status and accelerate disease progression. In HIV infection, MDSCs suppress anti-HIV immune responses and hamper immune reconstitution. Understanding the factors and mechanisms of MDSC expansion during HIV infection is central to understanding the pathophysiology of HIV infection. This may pave the way to developing new therapeutic targets or strategies. In this work we addressed (i) the mechanisms that regulate MDSC expansion, (ii) the impact of antiretroviral therapy (ART) on the frequency of MDSCs during HIV infection; (iii) the impact of MDSCs on immune reconstitution during successful ART; and (iv) the potential of MDSCs as a therapeutic target.

Predictors and disturbances of sleep quality between men and women: results from a cross-sectional study in Jordan.

BACKGROUND: Sleep disturbances, a public health concern that may lead to critical physiological conditions, are associated with personal characteristics such as gender. Limited evidence is available from the Middle East population on the gender disparities in sleep quality. Therefore, the current study examined gender-specific differences in sleep quality and disturbances among Jordanian citizens. METHOD: A cross-sectional design was used to recruit a convenient sample of 1,092 adults from different Jordanian cities. Data was collected using a self-reported questionnaire comprising the Pittsburgh Sleep Quality Index (PSQI), which was distributed online via social media networks. The participants were categorized according to their global PSQI scores into poor (PSQI ≥ 5) and good sleepers (PSQI < 5). The analysis focused on finding differences between women and men in terms of sleep quality and the effects of demographic, lifestyle, and socioeconomic factors on reported sleep problems. RESULTS: Women were revealed to have a higher prevalence of all types of sleep disturbances than men. Women who were over 55 (compared to younger than 20 years), did not smoke, had multiple jobs or part-time employment (compared to unemployed women), and had a monthly income of more than 500 JD (compared to those with an income of < 500 JD) were less likely to experience poor sleep than other women. In contrast, men who neither smoked nor drank coffee, ate no sweets or only one to two pieces daily (compared to participants who ate more than two pieces daily), and worked fixed night shifts (compared to alternating shifts workers) were less likely to experience poor sleep than other men. CONCLUSION: This study builds a more nuanced understanding of how different demographic, lifestyle, and socioeconomic factors - such as a participant's age, time of working duty, income, daily sweet consumption, daily caffeine consumption, and smoking - affect the sleep quality of men and women. Thus, promoting a healthier lifestyle for both genders by modifying risk factors - such as smoking cessation, as well as reducing their intake of caffeine and sweets - is the first step toward improving their sleep quality. Further studies are needed to examine how the social role of Arabic women affects their sleep.

The Role of p53 in HIV Infection.

PURPOSE OF REVIEW: This review aims to elucidate the multifaceted role of the tumor suppressor protein p53 in the context of HIV infection. We explore how p53, a pivotal regulator of cellular processes, interacts with various facets of the HIV life cycle. Understanding these interactions could provide valuable insights into potential therapeutic interventions and the broader implications of p53 in viral infections. RECENT FINDINGS: Recent research has unveiled a complex interplay between p53 and HIV. Several reports have highlighted the involvement of p53 in restricting the replication of HIV within both immune and nonimmune cells. Various mechanisms have been suggested to unveil how p53 enforces this restriction on HIV replication. However, HIV has developed strategies to manipulate p53, benefiting its replication and evading host defenses. In summary, p53 plays a multifaceted role in HIV infection, impacting viral replication and disease progression. Recent findings underscore the importance of understanding the intricate interactions between p53 and HIV for the development of innovative therapeutic approaches. Manipulating p53 pathways may offer potential avenues to suppress viral replication and ameliorate immune dysfunction, ultimately contributing to the management of HIV/AIDS. Further research is warranted to fully exploit the therapeutic potential of p53 in the context of HIV infection.

CMTM6 as a master regulator of PD-L1.

Immune checkpoint proteins, such as programmed cell death receptor 1 (PD-1) and its ligand (PD-L1), play critical roles in the pathology of chronic inflammatory pathological conditions, particularly cancer. In addition, the activation of PD-1/PD-L1 pathway is involved in mediating resistance to certain anti-cancer chemo- and immuno-therapeutics. Unfortunately, targeting the PD-1/PD-L1 pathway by the available anti-PD-1/PD-L1 drugs can benefit only a small proportion of cancer patients. Thus, studying the factors that regulate the expression of these immune checkpoint proteins is of central importance in this context. Recent investigations have identified CMTM6 and, to a lesser extent, CMTM4, as master regulators of PD-L1 expression in various cancer cells. Understanding the mechanisms by which such proteins upregulate the expression of PD-L1 in tumor cells, and determining the potential regulators of CMTM6 expression in different types of cancers will accelerate the development of new therapeutic targets and/or lead to the enhancement of the currently available PD-1/PD-L1 blockade therapies.

Patterns and clinical outcomes of olfactory and gustatory disorders in six months: Prospective study of 1031 COVID-19 patients.

OBJECTIVE: This study aims to comprehensively evaluate olfactory and gustatory dysfunctions during the COVID-19 pandemic regarding onset, course, associated symptoms, prognosis and relation to patients' demographics, treatment received and other symptoms. PATIENTS& METHODS: This is a prospective study conducted on patients proven to be infected with COVID-19 and with olfactory/gustatory dysfunction symptoms. Detailed history was taken from each patient about the onset of this dysfunction, associated symptoms. Then follow-up survey was done after 6 months to evaluate the prognosis. RESULTS: 1031 patients were included in the study, aged 18 to 69 years old, with 31.8% were male. Olfactory/gustatory dysfunctions occurred after other COVID-19 symptoms in 43.5% of cases, occurred suddenly in 80.4% and gradually in 19.6%. These dysfunctions were anosmia & ageusia in 50.2%, hyposmia & hypogeusia in 23.3%, anosmia alone in 17.7%, phantosmia in 18%, Parosmia in 28.4%. In terms of recovery 6-month follow up, 680 patients (66%) recovered completely, 22.1% recovered partially while 11.9% did not recover. Most improvement occurred in the first two weeks. Headache, malaise, nasal obstruction and rhinorrhea were the commonest COVID-19 symptoms associated. CONCLUSION: Most recovery of olfactory/gustatory dysfunction in COVID-19 infection occurs at the first two weeks and is unrelated to patient demographics, treatment or olfactory training. Parosmia is an independent predictor for complete recovery, while phantosmia is significantly associated with lower probability of complete recovery.

The impact of MDSCs on the efficacy of preventive and therapeutic HIV vaccines.

In spite of four decades of research on human immunodeficiency virus (HIV), the virus remains a major health problem, affecting tens of millions of people around the world. As such, developing an effective preventive/protective and therapeutic vaccines against HIV are essential to prevent/limit the continuous spread of the virus as well as to control the disease progression and to completely eradicate the virus from HIV infected patients, respectively. There are several factors that have impeded the development of such vaccines, and we need to gain further insight into these factors in order to enhance our knowledge concerning the proper immune activation pathways in the hope of accelerating the development of the highly sought-after vaccine. Recently, new immune cell populations, namely the myeloid-derived suppressor cells (MDSCs), were added to the battle of HIV infection. Indeed, MDSCs seem to play a central role in determining the efficacy of therapeutic and preventive vaccines, especially because vaccines, in general, enhance immune responses, while as a potent immunosuppressor cell population, MDSCs, in turn, subvert and limit the activation of immune responses. Hence, in this work, we sought to address the role of MDSCs in the context of preventive/protective, as well as, therapeutic HIV vaccines.

Shoulder MR Arthrography: Comparative Evaluation of Three Different Contrast Injection Techniques Using an Anterior Approach.

BACKGROUND: MR arthrography (MRA) is commonly used in the assessment of shoulder internal derangements. Correct intra-articular contrast injection is required for this modality. Anterior injections under fluoroscopic, ultrasound-guidance, or without image-guidance have been described in the literature. However, no simultaneous comparison has been performed between the three techniques. PURPOSE: To compare the accuracy and performance of fluoroscopy (FL)-guided, ultrasound (US)-guided and non-image-guided intra-articular contrast injection via an anterior approach for performing shoulder MRA. STUDY TYPE: Prospective. SUBJECTS: Two-hundred and ten patients (180 men and 30 women; mean age, 33 ± 12 years; range 20-60 years) with clinically suspected shoulder pathology. FIELD STRENGTH/SEQUENCE: 1.5T/fat-suppressed T1 -weighted, T2 -weighted, and 3D-gradient-echo images. ASSESSMENT: Patients underwent shoulder MRA after anterior intra-articular contrast injection under FL- or US-guidance or without image-guidance. Patients were randomized among the three techniques with each group comprising 70. The techniques were compared according to the accuracy of intra-articular needle placement, attempts success rate, pain during and 24 hours after injection, procedure times, contrast extravasation rate, joint distension, and MRA diagnostic efficacy. Pain was assessed by the visual analog scale (VAS) pain-score. STATISTICAL TESTS: Pearson's chi-squared and Kruskal-Wallis tests. RESULTS: FL- and US-guided injections (100% accuracy) were significantly more accurate than non-image-guided (85.7% accuracy) (P < 0.05). US-guidance was the least painful, with statistical differences between image-guided and non-image-guided techniques regarding the first attempt success rate (95.7% and 92.8% for FL- and US-guided vs. 78.6% for blinded), VAS-score 24 hours-post-procedure (1.7 ± 1.7, and 1.5 ± 1.4 vs. 2.2 ± 1.4), procedure time (11.9 ± 1.6, and 7.4 ± 1.7 vs. 4.3 ± 0.76 minutes), and contrast extravasation rate (5.7%, and 8.6% vs. 30%) (all P < 0.05). Procedure time was also significantly different between FL and US-guidance (P < 0.05). DATA CONCLUSION: Imaging-guided injections are more accurate and tolerable than non-image-guided and should be considered to confirm intra-articular needle position, hence adequate capsular distension and good diagnostic quality of shoulder MRA. US guidance is a less painful, rapid, and safe alternative to the FL approach. Evidence Level: 2 Technical Efficacy Stage: 5. J. MAGN. RESON. IMAGING 2021;53:481-490.

Imaging spectrum of acute invasive fungal rhino-orbital-cerebral sinusitis in COVID-19 patients: A case series and a review of literature.

BACKGROUND: The incidence of devastating opportunistic coinfections in patients with COVID-19 infection, their imaging features and their morbidity and mortality consequences need to be unraveled. METHODS: This is a case series presenting the radiologic features and clinical presentation of acute invasive fungal rhino-orbital-cerebral sinusitis (AIFS) in eight hospitalized patients with confirmed COVID-19 infection. RESULTS: Our patient cohort presented with symptoms of the invasive fungal disease within 12-35 days from their initial presentation with COVID-19 infection. The cross-sectional imaging features of AIFS associated with COVID-19 infection do not differ from those reported in the literature for AIFS associated with other risk factors, yet our patients had features of aggressive late-stage forms with high morbidity and mortality rate. CONCLUSION: AIFS is a possible encounter in patients with COVID-19 patients and radiologists should be familiar with its imaging features.

Cytosolic carnitine acetyltransferase as a source of cytosolic acetyl-CoA: a possible mechanism for regulation of cardiac energy metabolism.

The role of carnitine acetyltransferase (CrAT) in regulating cardiac energy metabolism is poorly understood. CrAT modulates mitochondrial acetyl-CoA/CoA (coenzyme A) ratios, thus regulating pyruvate dehydrogenase activity and glucose oxidation. Here, we propose that cardiac CrAT also provides cytosolic acetyl-CoA for the production of malonyl-CoA, a potent inhibitor of fatty acid oxidation. We show that in the murine cardiomyocyte cytosol, reverse CrAT activity (RCrAT, producing acetyl-CoA) is higher compared with the liver, which primarily uses ATP-citrate lyase to produce cytosolic acetyl-CoA for lipogenesis. The heart displayed a lower RCrAT Km for CoA compared with the liver. Furthermore, cytosolic RCrAT accounted for 4.6 ± 0.7% of total activity in heart tissue and 12.7 ± 0.2% in H9C2 cells, while highly purified heart cytosolic fractions showed significant CrAT protein levels. To investigate the relationship between CrAT and acetyl-CoA carboxylase (ACC), the cytosolic enzyme catalyzing malonyl-CoA production from acetyl-CoA, we studied ACC2-knockout mouse hearts which showed decreased CrAT protein levels and activity, associated with increased palmitate oxidation and acetyl-CoA/CoA ratio compared with controls. Conversely, feeding mice a high-fat diet for 10 weeks increased cardiac CrAT protein levels and activity, associated with a reduced acetyl-CoA/CoA ratio and glucose oxidation. These data support the presence of a cytosolic CrAT with a low Km for CoA, favoring the formation of cytosolic acetyl-CoA, providing an additional source to the classical ATP-citrate lyase pathway, and that there is an inverse relation between CrAT and the ratio of acetyl-CoA/CoA as evident in conditions affecting the regulation of cardiac energy metabolism.

The role of polymorphonuclear neutrophils during HIV-1 infection.

It is well-recognized that human immunodeficiency virus type-1 (HIV-1) mainly targets CD4+ T cells and macrophages. Nonetheless, during the past three decades, a huge number of studies have reported that HIV-1 can directly or indirectly target other cellular components of the immune system including CD8+ T cells, B cells, dendritic cells, natural killer cells, and polymorphonuclear neutrophils (PMNs), among others. PMNs are the most abundant leukocytes in the human circulation, and are known to play principal roles in the elimination of invading pathogens, regulating different immune responses, healing of injured tissues, and maintaining mucosal homeostasis. Until recently, little was known about the impact of HIV-1 infection on PMNs as well as the impact of PMNs on HIV-1 disease progression. This is because early studies focused on neutropenia and recurrent microbial infections, particularly, during advanced disease. However, recent studies have extended the investigation area to cover new aspects of the interactions between HIV-1 and PMNs. This review aims to summarize these advances and address the impact of HIV-1 infection on PMNs as well as the impact of PMNs on HIV-1 disease progression to better understand the pathophysiology of HIV-1 infection.

An integrated approach based on HFE-D, GIS techniques, GQISWI, and statistical analysis for the assessment of potential seawater intrusion: coastal multilayered aquifer of Ghaemshahr-Juybar (Mazandaran, Iran).

The overexploitation of coastal aquifers is one of the important reasons for the salinity of groundwater due to seawater intrusion (SWI). This study assesses the hydrochemical changes of the Ghaemshahr-Juybar (GH.-J.) plain. For this purpose, specific statistical methods, modified Piper diagram groundwater quality indicators ([Formula: see text] and [Formula: see text]), groundwater quality index specific to seawater intrusion ([Formula: see text]), and hydrochemical facies evolution diagram (HFE-D) along with GIS (Geographic Information System) techniques were applied to identify the spatiotemporal changes of salinity in coastal multilayer alluvial aquifer. The results show that the chemical composition in the GH.-J. aquifer is basically controlled by three main factors: (1) Caspian SWI and fossil saltwater penetration from an underlying layer, (2) reverse cation exchange process, and (3) feeding by domestic sewage, agricultural activities, and use of nitrate chemical fertilizers. The investigation of the hydrogeochemical facies evolution process shows that due to the reduction of extraction from wells, saltwater infiltration has significantly decreased. Therefore, according to the geological and lithological conditions of the aquifer and exposure to seawater, it is possible to prevent the entry of saltwater from the confined aquifer into the unconfined aquifer and the saltwater intrusion by developing well optimal operation policies in order to control withdrawal from semi-deep wells and the elimination of deep wells. This practical approach to managing the salinity of coastal aquifers is suitable for the allocating groundwater resources and for use in the development of aquifer simulation models.

Quality and Readability of Online Health Information on Common Urologic Cancers: Assessing Barriers to Health Literacy in Urologic Oncology.

INTRODUCTION: A growing number of Americans search online for health information related to urologic oncologic care each year. The American Medical Association recommends that medical information be written at a maximum sixth-grade level in order to be comprehensible by the majority of patients. As such, it is important to assess the quality and readability of online patient education material that patients are being exposed to. METHODS: A Google search was performed using the terms "testicular cancer," "prostate cancer," "kidney cancer," and "bladder cancer," and the top 30 results for each were reviewed. Websites were categorized based on their source. Readability was assessed using the Flesch-Kincaid Grade Level, the Gunning Frequency of Gobbledygook, and the Simple Measure of Gobbledygook indices. Quality was assessed using the DISCERN Quality Index (1-5 scale). RESULTS: A total of 91 websites were included in our analysis. On average, online health information pertaining to urologic cancers is written at a 10th- to 11th-grade reading level, which is significantly higher than that of an average American adult and that recommended by the American Medical Association (P < .01). The overall quality of websites was 3.4 ± 0.7, representing moderate to high quality. There was no significant difference in readability based on cancer type or information source. CONCLUSIONS: Despite being of moderate to high quality, online patient education materials related to common urologic cancers are often written at a grade level that exceeds the reading level of an average American adult. This presents as a barrier to online health literacy and calls into question the utility of these resources.

Experiences on health-related quality of life of Jordanian patients living with heart failure: A qualitative study.

BACKGROUND: Quantitative studies have provided valuable statistical insights into Health-Related Quality of Life (HRQoL) among patients with Heart Failure (HF), yet they often lack the depth to fully capture the nuanced, subjective experiences of living with HF particularly in the specific context of Jordan. This study explores the personal narratives of HF patients to understand the full impact of HF on their daily lives, revealing HRQoL aspects that quantitative metrics often miss. This is crucial in developing regions, where the increasing prevalence of HF intersects with local healthcare practices, cultural views, and patient expectations, providing key insights for tailored interventions and better patient care. METHODS: Utilizing a phenomenological qualitative design, this study conducted face-to-face semi-structured interviews with 25 HF patients to deeply explore their lived experiences. Thematic analysis was employed to identify major themes related to their perceptions of HF as a disease, its impact on various HRQoL domains, and their recommended strategies to enhance HRQoL. RESULTS: The study involved 25 participants (13 males, 12 females), aged 26-88 years (mean 63), with diverse education and heart failure (HF) severities. It revealed three themes: HF perceptions, its impact on health-related quality of life (HRQoL) across physical, psychosocial, spiritual, cognitive, and economic domains, and HRQoL improvement strategies. Participants had varied HF knowledge; some lacked basic understanding. The physical impact was most significant, affecting daily life and causing symptoms like breathing difficulties, coughing, edema, and fatigue. This physical aspect influenced their psychosocial and spiritual lives, cognitive functions, and economic stability, leading to fear, frustration, worry, social isolation, spiritual and cognitive challenges, and employment problems. CONCLUSIONS: The results underscores the need for holistic healthcare approaches, integrating medical, psychological, and social support. Key recommendations include integrated care models, comprehensive patient education, support networks, and policy interventions to enhance HF patient care.

Endoscopic Assisted Caldwell-Luc Approach for Total Excision of an Extensive Aneurysmal Bony Cyst of the Maxillary Sinus.

Aneurysmal bone cysts (ABCs) are uncommon lesions in head and neck area that could be primary or secondary in origin. The main problem with the traditional curettage and debridement is the high rates of recurrence, and cosmetic disfigurement with the open approach. In this article, we describe the use of a combined endoscopic sinus surgery and endoscopic assisted Caldwell approach to achieve a complete surgical excision of left maxillary sinus ABC extending to the left infratemporal fossa, and to avoid facial disfigurement in a 13-year-old female patient presented to our hospital with diplopia, facial pain, and headache. The patient had uneventful post-operative recovery period with resolution of the presenting symptoms with no complications. Hence, we recommend this combined endoscopic surgical approach in such cases.

Multi-user conflict resolution mechanisms for smart home environments.

Context-awareness is a pervasive computing enabling technology that allows context-aware applications to respond to multiple contexts such as activity, location, temperature, and so on. When many users attempt to access the same context-aware application, user conflicts may emerge. This issue is emphasized, and a conflict resolution approach is presented to address it. Although there are other conflict resolution approaches in the literature, the one presented here is unique in that it considers the users' special cases such as their sickness, examinations, and so on when resolving conflicts. The proposed approach is helpful when several users with different special cases try to access the same context-aware application. To demonstrate the usefulness of the proposed approach, a conflict manager is integrated with the UbiREAL simulated context-aware home environment. The integrated conflict manager resolves conflicts by taking users special cases into account and employing either automated, mediated, or hybrid conflict resolution approaches. The evaluation of the proposed approach demonstrates that users are satisfied with it and that it is critical and essential to employ users' special cases in detecting and resolving users conflicts.

Thymoquinone, piperine, and sorafenib combinations attenuate liver and breast cancers progression: epigenetic and molecular docking approaches.

BACKGROUND: Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells. METHODS: We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3. RESULTS: Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death. CONCLUSION: This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.

Primary Retroperitoneal Lymph Node Dissection for Stage II Seminoma: Is Surgery the New Path Forward?

PURPOSE: On the basis of National Comprehensive Cancer Network guidelines, clinical stage (CS) II seminoma is treated with radiotherapy or chemotherapy. Primary retroperitoneal lymph node dissection (RPLND) demonstrated recent success as first-line therapy for RP-only disease. Our aim was to confirm surgical efficacy and evaluate recurrences after primary RPLND for CS IIA/IIB seminoma to determine if various clinical factors could predict recurrences. PATIENTS AND METHODS: Patients who underwent primary RPLND for seminoma from 2014 to 2021 were identified. All patients had at least 6 months of follow-up. Nineteen patients were part of a clinical trial. Patients receiving adjuvant chemotherapy were excluded from Kaplan-Meier recurrence-free survival (RFS) analysis. RESULTS: We identified 67 patients who underwent RPLND for RP-only seminoma. One patient had pN0 disease. Median follow-up time after RPLND was 22.4 months (interquartile range, 12.3-36.1 months) and 11 patients were found to have a recurrence. The 2-year RFS for RPLND-only patients without adjuvant chemotherapy was 80.2%. Patients who developed RP disease for a period > 12 months had the lowest chance of recurrence, with a 2-year RFS of 92.2%. Seven initial CS II patients were on surveillance for 3-12 months before surgery and no patients experienced recurrence. Pathologic nodal stage and high-risk factors such as tumor size > 4 cm or rete testis invasion of the orchiectomy specimen did not affect recurrence. CONCLUSION: CS II seminoma can be treated with surgery to avoid rigors of chemotherapy or radiotherapy. Patients with delayed development of CS II disease (> 12 months) had the best surgical results. Patients may present with borderline CS II disease, and careful surveillance may avoid overtreatment. Further study on patient selection and extent of dissection remains uncertain and warrants further investigation.

Egyptian hemodialysis patients' willingness to receive the COVID-19 vaccine booster dose: a multicenter survey.

BACKGROUND: Health authorities have struggled to increase vaccination uptake since the COVID-19 vaccines became available. However, there have been increasing concerns about declining immunity after the initial COVID-19 vaccination with the emergence of new variants. Booster doses were implemented as a complementary policy to increase protection against COVID-19. Egyptian hemodialysis (HD) patients have shown a high rate of hesitancy to COVID-19 primary vaccination, yet their willingness to receive booster doses is unknown. This study aimed to assess COVID-19 vaccine booster hesitancy and its associated factors in Egyptian HD patients. METHODS: A face-to-face interview was conducted with closed-ended questionnaires distributed to healthcare workers in seven Egyptian HD centers, mainly located in three Egyptian governorates, between the 7th of  March and the 7th of April 2022. RESULTS: Among 691 chronic HD patients, 49.3% (n = 341) were willing to take the booster dose. The main reason for booster hesitancy was the opinion that a booster dose is unnecessary (n = 83, 44.9%). Booster vaccine hesitancy was associated with female gender, younger age, being single, Alexandria and urban residency, the use of a tunneled dialysis catheter, not being fully vaccinated against COVID-19. Odds of booster hesitancy were higher among participants who did not receive full COVID-19 vaccination and among those who were not planning to take the influenza vaccine (10.8 and 4.2, respectively). CONCLUSION: COVID-19 booster-dose hesitancy among HD patients in Egypt represents a major concern, is associated with vaccine hesitancy with respect to other vaccines and emphasizes the need to develop effective strategies to increase vaccine uptake.

Does pathological sub stratification of T2 bladder cancer predict outcome in a contemporary pure urothelial carcinoma cohort?

INTRODUCTION: Studies evaluating outcomes in bladder cancer sub stratified into T2a and T2b pathologic staging have demonstrated inconsistent results. Survival outcomes in a cohort of pure urothelial carcinoma patient undergoing radical cystectomy were evaluated to determine the prognostic value of T2 sub staging. METHODS: Using our prospectively maintained institutional cystectomy database, we identified patients with pure urothelial carcinoma of the bladder, either pT2aN0 or pT2bN0. We excluded any patients with variant histology, patients that underwent neoadjuvant chemotherapy, and patients that had margin positive disease. Demographic and clinicopathologic data were collected, and Cox proportional hazard regression assessed overall survival (OS), cancer specific survival (CSS), and recurrence free survival (RFS). RESULTS: From 2001 to 2019, we identified 1,929 patients that underwent radical cystectomy, 61 patients had pT2a and 65 had pT2b pure urothelial carcinoma that met inclusion criteria. Only age (P = 0.02) and the initial transurethral resection of bladder tumor pathology (P < 0.01) were notably different when comparing the clinical characteristics of patients with pT2a and pT2b. No differences were noted in OS, CSS, or RFS between the 2 groups on Kaplan-Meier analysis. On univariate Cox regression analysis, age, TURBT stage, cystectomy pathology stage, carcinoma in situ, and lymphovascular invasion status, and Bacillus Calmette-Guérin therapy status was not found to be significant factors for OS, CSS, or RFS between patients with pT2aN0 or pT2bN0 tumors. CONCLUSION: Prior studies have sub stratified pT2a and pT2b, studying survival outcomes with equivocal results. Many of these studies included variant histology or use of chemotherapy in the analysis. Here, we identified a pure urothelial cohort to compare survival outcomes between pT2a and pT2b and found no difference in OS, CSS, and RFS.

The clinical and prognostic significance of CMTM6/PD-L1 in oncology.

The recent discovery of CMTM6 and to a lesser extent CMTM4, two members of the chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family, as master positive regulators of PD-L1 expression, the primary ligand of programmed cell death 1 (PD-1), on tumor and immune cells has opened new horizons for investigating the role of CMTM6/CMTM4 in different aspects of oncology including their clinical and prognostic values in different cancer types. The absence of a specific review article addressing the available results about the clinical and prognostic roles of CMTM6 alone and/or in combination with PD-L1 in cancer has encouraged us to write this paper.