CAR-T cell therapy: Efficacy in management of cancers, adverse effects, dose-limiting toxicities and long-term follow up.

Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a groundbreaking and highly promising approach for the management of cancer. This paper reviews the efficacy of CAR-T therapy in the treatment of various hematological malignancies, also, with a mention of its effect on solid tumors, for which they have not received FDA approval yet. Different common and uncommon side effects are also discussed in this paper, with attention to the effect of each drug separately. By reviewing the recommendations of the FDA for CAR-T therapy research, we have extensively discussed dose-limiting toxicities. This further highlights the need for precise dosing strategies, striking a balance between therapeutic benefits and potential risks. Additionally, we reviewed the long-term follow-up of patients receiving CAR-T therapy to gain valuable insights into response durability and late-onset effects.

Impact of birth weight to placental weight ratio and other perinatal risk factors on left ventricular dimensions in newborns: a prospective cohort analysis.

OBJECTIVES: To investigate the association between birth weight to placental weight (BW/PW) ratio, and echocardiographic left ventricle (LV) morphology at birth, while accounting for other relevant perinatal factors. METHODS: A prospective cohort study was conducted on neonates at NewYork-Presbyterian Brooklyn Methodist Hospital from 2014 to 2018, categorized by their BW/PW percentile. Missing data were imputed with principal component analysis. Chi-squared and one-way analysis of variance were used to compare BW/PW groups and the best regression model was selected using a genetic and backward stepwise algorithm. RESULTS: We analyzed 827 neonates in three BW/PW groups: small (n=16), normal (n=488), and large (n=323). Placental thickness and smallest diameter were positively correlated with several LV parameters, including inter-ventricular septal thickness during diastole (IVSd) (p=0.002, p<0.001) and systole (IVSs) (p=0.001, p<0.001), LV posterior wall thickness at end of diastole (LVPWd) (p=0.003, p<0.001) and systole (LVPWs) (p<0.001, p<0.001), LV mass (p=0.017, p<0.001), and LV mass/volume (p=0.011, p<0.001). The BW/PW ratio correlated with an increased shortening fraction (estimate=0.29, 95 % CI 0.03-0.55, p=0.027). PW correlated with IVSs (p=0.019), while the longest placental diameter was linked to a decrease in LV internal dimension during diastole (LVIDd) (estimate=-0.07, p=0.039), LV mass (estimate=-0.11, p=0.024), and LV mass/volume (estimate=-0.55, p=0.005). CONCLUSIONS: This study found that several placental factors, including the BW/PW ratio, can independently affect LV dimension and morphology, highlighting the importance of fetal growth and placental health in the physiological adaptation of the fetal heart. More research is needed to establish causation and inform newborn prevention strategies.

Early vs delayed insertion of penile prosthesis in patients with refractory priapism: a systematic review and meta-analysis.

INTRODUCTION: Refractory priapism, characterized by persistent and prolonged painful erections despite initial treatment maneuvers, can significantly impair erectile function secondary to ischemia-induced corporal tissue fibrosis. These patients will likely require subsequent penile prosthesis (PP) surgery to regain sexual activity, yet consensus regarding the optimal timing of implantation remains lacking. OBJECTIVES: To evaluate and compare the clinical outcomes associated with early vs delayed PP implantation in individuals with priapism-induced erectile dysfunction (ED). METHODS: We included studies that focused on refractory priapism leading to ED and its management with PP implantation. We assessed cohort study bias with a risk-of-bias tool and case series bias with the modified Newcastle-Ottawa Scale. Pooled odds ratios (ORs) were calculated by a fixed-effect model. RESULTS: We included 9 studies, comprising 4 cohort studies and 5 case series, involving a total of 278 patients. Total complications were higher in the delayed group (OR, 4.16; 95% CI, 2.77-6.26). Fibrosis was significantly more pronounced in the delayed group (OR, 118.18; 95% CI, 20.06-696.32). The odds of erosion, infections, and penile injury did not show statistically significant differences between the groups (OR, 2.52 [95% CI, 0.67-9.49], 0.89 [0.38-2.10], 1.83 [0.79-4.26], respectively). Patients' satisfaction resulted in a pooled OR of 0.15 (95% CI, 0.04-0.49) in favor of the early PP insertion group. CONCLUSION: The results from this study favor an early approach to ED (within 30 days) following ischemic priapism. However, it is important to consider patients' preferences, values, and psychological factors to make an informed decision.

The Contemporary Role of Hematopoietic Stem Cell Transplantation in the Management of Chronic Myeloid Leukemia: Is It the Same in All Settings?

Hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) patients has transitioned from the standard of care to a treatment option limited to those with unsatisfactory tyrosine kinase inhibitor (TKI) responses and advanced disease stages. In recent years, the threshold for undergoing HSCT has increased. Most CML patients now have life expectancies comparable to the general population, and therefore, the goal of therapy is shifting toward achieving treatment-free remission (TFR). While TKI discontinuation trials in CML show potential for achieving TFR, relapse risk is high, affirming allogeneic HSCT as the sole curative treatment. HSCT should be incorporated into treatment algorithms from the time of diagnosis and, in some patients, evaluated as soon as possible. In this review, we will look at some of the recent advances in HSCT, as well as its indication in the era of aiming for TFR in the presence of TKIs in CML.

Male Fertility and Fatherhood in Chronic Myeloid Leukemia: Current Understanding and Future Perspectives.

Chronic myeloid leukemia (CML), while traditionally a disease of the elderly, has recently risen in incidence among younger patients. Hence, fertility concerns have emerged considering the disease process and treatments, especially with the current scarce and conflicting recommendations. This review explores the impact of CML treatments including the first-line tyrosine kinase inhibitors (TKIs) and other treatments on male fertility in chronic myeloid leukemia (CML) patients. The aim of this review was to compile the available evidence on male fertility to ultimately tailor treatment plans for male CML patients for whom fertility and future chances for conception pose a concern. The data available on the conventional and newer TKIs to address fertility concerns were reviewed, particularly the potential long- and short-term effects. Also, the possible side effects on subsequent generations were a crucial focus point of this review to reach a more comprehensive CML management approach. We found and compared the evidence on TKIs approved to treat CML. We also reported the effects of hydroxyurea, interferon, and transplantation, which are considered second-line treatments. Our findings suggest that these drugs might have an undiscovered effect on fertility. More research with larger sample sizes and longer follow-up periods is essential to solidify our understanding of these effects.

Phenotypic switching of vascular smooth muscle cells in atherosclerosis, hypertension, and aortic dissection.

Vascular smooth muscle cells (VSMCs) play a critical role in regulating vasotone, and their phenotypic plasticity is a key contributor to the pathogenesis of various vascular diseases. Two main VSMC phenotypes have been well described: contractile and synthetic. Contractile VSMCs are typically found in the tunica media of the vessel wall, and are responsible for regulating vascular tone and diameter. Synthetic VSMCs, on the other hand, are typically found in the tunica intima and adventitia, and are involved in vascular repair and remodeling. Switching between contractile and synthetic phenotypes occurs in response to various insults and stimuli, such as injury or inflammation, and this allows VSMCs to adapt to changing environmental cues and regulate vascular tone, growth, and repair. Furthermore, VSMCs can also switch to osteoblast-like and chondrocyte-like cell phenotypes, which may contribute to vascular calcification and other pathological processes like the formation of atherosclerotic plaques. This provides discusses the mechanisms that regulate VSMC phenotypic switching and its role in the development of vascular diseases. A better understanding of these processes is essential for the development of effective diagnostic and therapeutic strategies.

Emerging roles of activating transcription factor 2 in the development of breast cancer: a comprehensive review.

Activating transcription factor 2 (ATF2) is a member of the leucine zipper family of DNA binding proteins that are responsible for regulating various genes that play an essential role in major biological and cellular functions. Since ATF2 plays a vital role in cellular proliferation and apoptosis, it is believed that it greatly affects the development of breast cancers. However, its exact role in breast cancer is incompletely understood. It remains a subject of debate, ambiguity, and continuous research. Several studies have suggested the role of ATF2 as an oncogene, promoting cellular proliferation and worsening the outcome of cancers. In contrast, other studies have postulated that ATF2 plays a tumor suppressive role in estrogen receptor-positive breast cancer. The ambiguity surrounding its role in breast cancer is the reason why there is an influx of recent studies and research in this area. In this narrative review, we investigate several studies that have been published about the role of ATF2 in breast cancer. We also explore studies that have examined the association between ATF2 and endocrine therapy resistance. ATF2 has been suggested to modulate estrogen receptor (ER) expression and activity, potentially affecting tamoxifen sensitivity in breast cancer cells. Therefore, the role of ATF2 in DNA repair mechanisms and drug resistance has been deeply explored in this review. Additionally, there are numerous ongoing clinical trials exploring the effect of targeting ATF2 pathways and mechanisms on the outcome of breast cancers, some of which we have discussed. The studies and clinical trials that are being conducted to understand the multifaceted role of ATF2 and its signaling pathways may provide valuable insight for developing efficient targeted therapeutic solutions to enhance the outcomes of breast cancer and overcome endocrine resistance. We suggest further research to elucidate the dual roles of ATF2 in breast cancer and potential therapeutic therapies for its treatment.

Perinatal factors impacting echocardiographic left ventricular measurement in small for gestational age infants: a prospective cohort study.

INTRODUCTION: Infants born small for gestational age (SGA) have an increased risk of developing various cardiovascular complications. While many influencing factors can be adjusted or adapt over time, congenital factors also have a significant role. This study, therefore, seeks to explore the effect of perinatal factors on the left ventricular (LV) parameters in SGA infants, as assessed immediately after birth. METHODS AND MATERIALS: This single-center prospective cohort study, conducted between 2014 and 2018, involved healthy SGA newborns born > 35 weeks' gestation, delivered at New York-Presbyterian Brooklyn Methodist Hospital, and a gestational age (GA)-matched control group of appropriate for gestational age (AGA) infants. Data analysis was performed using multivariate linear regression in STATA. RESULTS: The study enrolled 528 neonates, 114 SGA and 414 AGA. SGA infants exhibited a mean GA of 38.05 weeks (vs. 38.54), higher male representation (69.3% vs. 51.5%), lower birth weight (BW) (2318g vs 3381g), lower Apgar scores at birth, and a higher rate of neonatal intensive care unit admission compared to AGA infants (41.2% vs.18.9%; p<0.001). Furthermore, SGA infants were more likely to be born to nulliparous women (63.16% vs. 38.16%; p<0.001), with lower body mass index (BMI) (29.8 vs. 31.7; p=0.004), a lower prevalence of gestational maternal diabetes (GDM) (14.9 % vs. 35.5%; p<0.001), and a higher prevalence of preeclampsia (18.4 % vs. 6.52%; p<0.001). BW was identified as the most significant predictor affecting most LV parameters in this study (p<0.001), except shortening fraction, asymmetric interventricular septal hypertrophy and Inter-ventricular septal thickness/LV posterior wall ratio (IVS/LVPW). Lower GA (coefficient = -0.09, p=0.002), insulin use in GDM (coefficient = 0.39, p=0.014), and low APGAR scores at 1 minute (coefficient = -0.07, p<0.001) were significant predictors of IVS during diastole (R-squared [R2]=0.24). High maternal BMI is marginally associated with LVPW during systole (R2=0.27, coefficient = 0.01, p=0.050), while male sex was a significant predictor of LV internal dimension during diastole (R2=0.29, p=0.033). CONCLUSION: This study highlights the significant influence of perinatal factors on LV parameters in SGA infants, with BW being the most influential factor. Although LV morphology alone may not predict future cardiovascular risk in the SGA population, further research is needed to develop effective strategies for long-term cardiovascular health management in this population.

Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Triple-Negative Breast Cancer (TNBC) is a lethal subtype of breast cancer with limited treatment options. The purpose of this Network Meta-Analysis (NMA) is to compare the efficacy and safety of inhibitors of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in treating TNBC. METHODS: Our search strategy was used in six databases: PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature database, Embase, Scopus, and Web of Science up to November 2nd, 2022, as well as a thorough search in the most used trial registries. We included phase II and III randomized controlled trials that looked at the efficacy of PD-1/PD-L1 inhibitors in the treatment of TNBC and reported either Overall Survival (OS), Progression-Free Survival (PFS), or pathological Complete Response (pCR). The risk of bias was assessed utilizing Cochrane's risk of bias 2 tool, and the statistical analysis was performed using a frequentist contrast-based method for NMA by employing standard pairwise meta-analysis applying random effects model. RESULTS: 12 trials (5324 patients) were included in our NMA including seven phase III trials. Pembrolizumab in a neoadjuvant setting achieved a pooled OS of 0.82 (95% Confidence Interval (CI) 0.65 to 1.03), a PFS of 0.82 (95% CI 0.71 to 0.94) and a pCR 2.79 (95% CI 1.07 to 7.24) compared to Atezolizumab's OS of 0.92 (95% CI 0.74 to 1.15), PFS of 0.82 (95% CI 0.69 to 0.97), and pCR of 1.94 (95% CI 0.86 to 4.37). Atezolizumab had less grade ≥ 3 adverse events (OR 1.48, 95% CI 0.90 to 2.42) than Pembrolizumab (OR 1.90, 95% CI 1.08 to 3.33) in the neoadjuvant setting. CONCLUSIONS: PD-1/PD-L1 inhibitors exhibited varying efficacy in terms of OS, PFS, and pCR. They were associated with an increase in immune-related adverse effects. When used early in the course of TNBC, PD-1/PD-L1 inhibitors exert their maximum benefit. Durvalumab as a maintenance treatment instead of chemotherapy has shown promising outcomes. Future studies should focus on PD-L1 expression status and TNBC subtypes, since these factors may contribute to the design of individualized TNBC therapy regimens. Systematic review registration PROSPERO Identifier: CRD42022380712.

Clinicopathological and prognostic value of chemokine receptor CCR7 expression in head and neck squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to identify the clinicopathological characteristics and prognostic value of CC chemokine receptor 7 (CCR7) expression in patients with head and neck squamous cell carcinoma (HNSSC). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in this meta-analysis. Up to the 2nd of July 2022 a search was conducted using five databases: PubMed, Embase, Scopus, ProQuest, and Web of Science. The methodological standards for the epidemiological research scale were used to assess the quality of the included articles, and Stata software was used to synthesize the meta-analysis. RESULTS: We considered 13 of the 615 studies which included 1005 HNSCC patients. High expression of CCR7 increased the pooled odds ratio (OR) of advanced stage, tumor size, metastasis and recurrence by 2.82 [95% confidence interval (CI) 1.84 to 4.33], 2.48 (95% CI 1.68, to 3.67), 3.57, 95% CI 2.25 to 5.05) and 3.93 (95% CI 2.03 to 7.64), respectively. High CCR7 reduced overall patient survival [hazard ratio 2.62 (95% CI 1.59 to 4.32)]. CONCLUSION: This study showed that high expression of CCR7 in HNSCC tumors was significantly associated with worse clinicopathological and survival outcomes, suggesting that CCR7 and its pathway could be potential therapeutic strategies for HNSCC.

Human Papillomaviruses-Related Cancers: An Update on the Presence and Prevention Strategies in the Middle East and North African Regions.

The human papillomavirus (HPV) is a non-enveloped double-stranded DNA virus capable of infecting skin and mucosa epithelial cells. Commonly, HPV infection is associated with sexually transmitted diseases and is considered the leading cause of cervical cancer and other carcinomas of the anogenital tract. However, several studies reported their involvement in cancers of non-sexual regions, including colorectal, head and neck, and breast cancers. There are several studies from the Middle East and North Africa (MENA) regions on the potential association between high-risk HPVs and cancer; nevertheless, there are limited studies that address the significance of HPV vaccination as a potential guard against these cancers. In the current review, we present a comprehensive description of the current HPV-associated cancers prevalence rates in the MENA region, demonstrating their steady increase with time, especially in African regions. Moreover, we discuss the potential impact of vaccination against HPV infections and its outcome on human health in this region.

Clinical Implications of COVID-19 Presence in CSF: Systematic Review of Case Reports.

This systematic review focused on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients that had detected SARS-CoV-2 virus in cerebrospinal fluid (CSF). A systematic literature search was carried out in PubMed, Embase, Scopus, Web of Science, Medrxiv, and Biorxiv databases from inception to 19 December 2021. Case reports or case series involving patients with proved SARS-CoV-2 presence in CSF by polymerize chain reaction were included. Our search strategy produced 23 articles documenting a total of 23 patients with positive SARS-CoV-2 in the CSF. Fever (55%) was the most common symptom, followed by headaches (41%), cough (32%), and vomiting/nausea (32%). The majority of the cases included was encephalitis (57%), 8 of which were confirmed by magnetic resonance imaging. The second most prevalent presentation was meningitis. The cerebral spinal fluid analysis found disparities in protein levels and normal glucose levels in most cases. This study demonstrates that SARS-CoV-2 can enter the nervous system via various routes and cause CNS infection symptoms. SARS-CoV-2 has been shown to infect the CNS even when no respiratory symptoms are present and nasopharyngeal swabs are negative. As a result, SARS-CoV-2 should be considered as a possible cause of CNS infection and tested for in the CSF.

Accuracy of artificial intelligence-assisted detection of Oral Squamous Cell Carcinoma: A systematic review and meta-analysis.

Oral Squamous Cell Carcinoma (OSCC) is an aggressive tumor with a poor prognosis. Accurate and timely diagnosis is therefore essential for reducing the burden of advanced disease and improving outcomes. In this meta-analysis, we evaluated the accuracy of artificial intelligence (AI)-assisted technologies in detecting OSCC. We included studies that validated any diagnostic modality that used AI to detect OSCC. A search was performed in six databases: PubMed, Embase, Scopus, Cochrane Library, ProQuest, and Web of Science up to 15 Mar 2022. The Quality Assessment Tool for Diagnostic Accuracy Studies was used to evaluate the included studies' quality, while the Split Component Synthesis method was utilized to quantitatively synthesize the pooled diagnostic efficacy estimates. We considered 16 out of the 566 yielded studies, which included twelve different AI models with a total of 6606 samples. The summary sensitivity, summary specificity, positive and negative likelihood ratios as well as the pooled diagnostic odds ratio were 92.0 % (95 % confidence interval [CI] 86.7-95.4 %), 91.9 % (95 % CI 86.5-95.3 %), 11.4 (95 % CI 6.74-19.2), 0.087 (95 % CI 0.051-0.146) and 132 (95 % CI 62.6-277), respectively. Our findings support the capability of AI-assisted systems to detect OSCC with high accuracy, potentially aiding the histopathological examination in early diagnosis, yet more prospective studies are needed to justify their use in the real population.

HPV and Recurrent Respiratory Papillomatosis: A Brief Review.

Recurrent Respiratory Papillomatosis (RRP) is a rare but severe manifestation of human papillomavirus (HPV). As our knowledge about HPV infections has expanded, it has become possible to understand the course of RRP disease and unravel plausible efficient methods to manage the disease. However, the surge in reports on HPV has not been accompanied by a similar increase in research about RRP specifically. In this paper, we review the clinical manifestation and typical presentation of the illness. In addition, the pathogenesis and progression of the disease are described. On the other hand, we discuss the types of treatments currently available and future treatment strategies. The role of vaccination in both the prevention and treatment of RRP will also be reviewed. We believe this review is essential to update the general knowledge on RRP with the latest information available to date to enhance our understanding of RRP and its management.