The Oncological Safety of Submental Flap Reconstruction in Head-and-Neck Cancers: An Extended Follow-up Study.

Introduction: The oncological safety of a submental (SM) flap is thought to be controversial. The objective of our study was to validate our previous study regarding the oncological safety of SM flaps in oral cavity reconstruction. Materials and Methods: An electronic database was searched from 2015 to 2021 for all head-and-neck tumor patients, where reconstruction was performed using a SM flap. Results: Eighty-eight oral cavity squamous cell carcinoma patients, among whom 71 were males (81.8%), with a mean age of 55.3 years (range: 25-79 years), were retrieved from the database. The sites of involvement were 37 buccal mucosa, 27 lower alveolus, and 24 tongues. The mean follow-up was 33.5 months. The SM flap reconstruction was done for 88 patients; 3 had complete loss of flap, 17 had incomplete loss/partial necrosis, and 68 patients had uneventful recovery of the flap. We had 16 patients with local recurrence. Of these, 4 (4.5%) patients had clear margins and no lymphadenopathy at the level I at the final histopathology report. Conclusion: This study provides validation of the oncological safety of the SM flap and establishes that nodal positivity at level I alone does not contribute to recurrence at the primary site.

Incidence and Risk of Secondary Malignancy in Patients with Waldenström Macroglobulinemia: A Population-Based Analysis.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma which may predispose individuals to development of secondary malignancies (SMs). The Surveillance, Epidemiology, and End Results (SEER) database is a comprehensive registry of cancer patients in the United States reporting on a wide set of demographic variables. Using the SEER-18 dataset, analyzing patients from 2000 to 2018, we aimed to assess the incidence of SMs in WM patients. Patient characteristics such as gender, age, race, and latency were identified, and respective standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated to compare to the general population. Of the 4,112 eligible WM patients identified, SMs were reported in 699 (17%) patients. The overall risk of developing SM, second primary malignancy, and secondary hematological malignancy was significantly higher in WM patients compared to the general population. Our findings show that WM patients had a 53% higher risk of SMs relative to the general population, and an AER of 102.69 per 10,000. Although the exact mechanism is unclear, the risk of SM development may be due to genetic predisposition, immune dysregulation, or treatment-induced immune suppression.

Assessing Metal Exposure and Leaching from Discarded Cigarette Butts: Environmental Analysis and Integrated Waste Management Approaches.

Cigarette butts, often discarded as litter, are considered a common form of waste, containing a variety of pollutants within this hazardous residue. This study, which was designed to assess the environmental release of certain metals from cigarette butts, investigates a variety of scenarios under varying climatic conditions. Thus, in order to assess the level of metal contamination, samples of cigarette butts were collected in urban areas from seven popular brands in China, smoked artificially, and examined through graphite furnace atomic absorption (GF-AAS). The findings indicated mean concentrations of 1.77 for Cr, 2.88 for Ni, 12.93 for Cu, 24.25 for Zn, and 1.77 µg/g for Pb in the case of newly smoked butts. The emission of each of the metals increases to 8-10% when cigarette butts remain in the environment for an extended period of time. Furthermore, rainfall can accelerate metal leaching, reaching values of 18-20% compared to the controlled scenario. The worst-case scenario releases 2129.31 kg/year of metals into the environment, while the best-case scenario sees a lower release of 844.97 kg/year. The data reflect variations in metal emissions across different scenarios. There was also a strong correlation between cigarette butts in public spaces and cities. This research highlights the need to educate smokers and increase urban maintenance efficiency to reduce this litter and the metals it leaches into the environment.

Irinotecan dosing and pharmacogenomics: a comprehensive exploration based on UGT1A1 variants and emerging insights.

Irinotecan is a critical anticancer drug used to treat metastatic colorectal cancer and advanced pancreatic ductal adenocarcinoma by obstructing topoisomerase 1; however, it can cause minor-to-severe and life-threatening adverse effects. UDP glucuronosyltransferase family 1 member A1 (UGT1A1) polymorphisms increase the risk of irinotecan-induced neutropenia and diarrhea. Hence, screening for UGT1A1 polymorphisms before irinotecan-based chemotherapy is recommended to minimize toxicity, whereas liposomes offer the potential to deliver irinotecan with fewer side effects in patients with pancreatic ductal adenocarcinoma. This review presents a comprehensive overview of the effects of genotype-guided dosing of irinotecan on UGT1A1*28 and UGT1A1*6 variants, incorporating pharmacogenomic research, optimal regimens for metastatic colorectal and pancreatic cancer treatment using irinotecan, guidelines for toxicity reduction, and an evaluation of the cost-effectiveness of UGT1A1 genotype testing.

Geographic and Racial Disparities in Chimeric Antigen Receptor-T Cells and Bispecific Antibodies Trials Access for Diffuse Large B-Cell Lymphoma.

BACKGROUND: We investigate the geographical and racial disparities in accessing CAR-T and bispecific antibodies trials for DLBCL. MATERIALS AND METHODS: ClinicalTrials.gov was searched, and 75 trials with at least 1 open site in the US were included. 2020 US Census Bureau data was used to obtain data on race and ethnicity. SPSS version 26 was used for analysis. RESULTS: There were 62 CAR-T and 13 bispecific antibodies trials with 6221 enrolled or expected to enroll patients. Eighty-five percent of the clinical trials were only open in the US, and the majority 64% were pharmaceutical-funded. There were 126 unique study sites distributed over 31 states with 11 (0-51) mean number of trials per state and 4.5 (1-26) and 4.4 (1-24) mean number of CAR-T and bispecific antibodies trials per site, respectively. Southern states had the most number of trials 31%, followed by Midwestern 25%, Northeastern 24%, and Western 20%. The highest number of study locations were in California 13, New York 9, and Pennsylvania 9, while the highest number of open studies were in California 51, Texas 32, and New York 23. Twenty states had no open CAR-T or bispecific antibodies trials. Only 33% of African Americans (AA) lived in a county with a trial, and 7 out of 10 states with the highest proportion of AA residents (18.6%-41.4%) have no or less than 4 trial sites. Of the 62 counties analyzed, 92% were White predominant, while only 8% were AA predominant (P = .009). CONCLUSIONS: Strategies should be framed to address the observed disparities and to improve access.

Polyherbal extract improves glycometabolic control in alloxan-induced diabetic rats via down-regulating the MAPK/JNK pathway, modulating Nrf-2/Keap-1 expression, and stimulating insulin signaling.

Objectives: This study focused on the evaluation of antioxidant and antidiabetic activities of polyherbal extract (PHE), containing Cassia absus (L.), Gymnema sylvestre (R. Br.), Nigella sativa (L.), and Piper nigrum (L.), in alloxan-induced diabetes model. Materials and Methods: In vitro, HPLC characterization, DPPH scavenging assay, and α-amylase inhibition test were conducted. In vivo, acute oral toxicity of PHE was assessed. Alloxan-induced diabetic Wistar rats (n=6) were orally treated with PHE (200, 400, and 600 mg/kg/day) and glibenclamide (GLB; 10 mg/kg/day) for six consecutive weeks. Then, biochemical biomarkers, oxidative stress parameters, histopathological examination, and mRNA expression levels (RT-qPCR) were determined. Results: The presence of polyphenols in PHE was confirmed in correlation to marked DPPH scavenging (IC50: 1.60 mg/ml) and α-amylase inhibition (IC50: 0.82 mg/ml). PHE demonstrated no toxicity in rats up to a dose of 2000 mg/kg. In diabetic rats, PHE dose-dependently ameliorated the serum levels of glucose, insulin, glycated hemoglobin A1c (HbA1c), leptin, and glucokinase (GCK). Also, PHE substantially alleviated serum inflammatory markers (TNF-α and CRP) and oxidative stress indicators (MDA, SOD, and CAT) in pancreatic tissues. PHE, particularly at 600 mg/kg, attenuated cellular oxidative stress via modulating the mRNA expression levels of genes regulating MAPK/JNK (Mapk-8, Traf-4, and Traf-6) and Nrf-2/Keap-1 pathways and promoted insulin signaling through up-regulating insulin signaling cascade (Pdx-1, Ins-1, and Ins-2), as compared to GLB. Furthermore, histopathological findings supported the aforementioned results. Conclusion: Our study suggests that polyherbal extract has promising antioxidant and antidiabetic activities by modulating the MAPK/JNK, Nrf-2/Keap-1, and insulin signaling pathways.

Assessment of antiarthritic potential of Asparagus dumosus using formaldehyde and CFA-induced arthritic models in rats via modulation of oxidative stress biomarkers and mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2.

Medicinal plants play a pivotal role in the prevention of chronic non-communicable diseases including arthritis. Despite the traditional use of Asparagus dumosus in arthritis, it has not been studied yet for its effectiveness in arthritis. This study was aimed to explore the antiarthritic potential of A. dumosus in formaldehyde and complete Freund's adjuvant (CFA)-induced arthritic rats. Body weight, arthritic index, hepatic oxidative stress, hematological, biochemical and inflammatory markers were assessed using ELISA, whilst qRT-PCR studies were carried out for the mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2 genes. GCMS and HPLC analysis were performed to identify the secondary metabolites of A. dumosus. From day 8 to 28 post-administration of formaldehyde and CFA, oral administration of A. dumosus (600, 300 and 150 mg/kg) showed a noteworthy improvement (p < 0.001) in the body weights, immune organ weights, serum levels of rheumatoid (RA) factor, C-reactive protein, TNF-α and IL-6 levels in arthritic rats similar to the effect of piroxicam and methotrexate. Subsequently, the administration of A. dumosus to formaldehyde and CFA-challenged rats, caused a marked decrease (p < 0.001) in the mRNA expression of IL-1b, IL-6, OPG, RANKL, TNF-α and COX-2 genes in treated rats. Likewise, when assessed for antioxidant potential, A. dumosus produced a pronounced (p < 0.001) reduction in malondialdehyde (MDA) levels and hydrogen peroxide (H2O2) production, whilst a dose-dependent (p < 0.001) increase in catalase (CAT) and superoxide dismutase (SOD) activities was recorded. GCMS profiling of A. dumosus presented benzaldehyde, 3-hydroxy-4-methoxy-, 1-decanol and undecane as plant compositions, whereas HPLC fingerprinting displayed quercetin, benzaldehyde, 3-hydroxy-4-methoxy-, gallic acid and cinnamic acid as plants constituents. These results depict that A. dumosus possesses anti-arthritic effect mediated possibly through attenuation of arthritic indices, chronic inflammatory and oxidative stress biomarkers along with down-regulation in the mRNA expression of arthritic candid genes.

Survival Outcome in True Carcinoma of Unknown Primary (tCUP) with p16 + Cervical Metastasis.

Introduction Age and lymph node ratio have been attributed as independent predictors for survival and recurrence in carcinoma of unknown primary (CUP). Objective The purpose of this study was to analyze the prognostic value of p16 overexpression for CUP in the absence of true primary (TP). Methods The study involved 43 patients who underwent therapeutic lymph node dissection (LND) from 2000 to 2015 after all the diagnostic work up for CUP. Immunohistochemistry for p16 overexpression was performed. Cox proportional hazard regression analysis was used to analyze the prognostic impact on 5-year overall survival (OS) and recurrence-free survival (RFS). Results The male-to-female ratio was 5.1:1, with a median age of 62 years. The clinicopathological data, except for p16 overexpression, did not differ significantly in terms of 5-year OS and RFS. The Cox regression analysis proposed p16 positivity to be an independent prognosticator of regional recurrence-free survival (RRFS) (hazard ratio [HR] 6.180, p = 0.21). The median time to recurrence and death were 10 and 25 months, respectively. Conclusion Cervical metastasis with p16 overexpression is a significant prognostic factor of improved RFS after surgery in CUP. The prognostic significance of lymph node p16 positivity should be further studied.

Survival Outcomes and Patterns of Failure in Maxillary Alveolus Squamous Cell Carcinoma.

Introduction Squamous cell carcinoma (SCC) of the maxillary alveolus is a relatively rare disease. There is lack of data on this subsite as compared with other sites. The factors that affect survival in cases of maxillary alveolar SCC are tumor stage, local and cervical metastases, histological grading, and the margin status. Objectives To evaluate the overall survival (OS), the disease free survival (DFS), and the complex interaction and effects of margin status, histological differentiation, habits (such as smoking and the use of smokeless tobacco products), and cervical and distant metastases based on clinicopathological data. Methods We examined the electronic database at our hospital from 2003 to 2017. We included all cases with a histopathological diagnosis of SCC of the maxillary alveolus. Tumors originating primarily from the maxillary alveolus were included, while those originating from adjacent subsites, like the hard palate, the buccal mucosa or the maxillary sinus were excluded. We also excluded all the patients who were not operated on with a curative intent. Results More than half of the patients had stage-IV tumors at the time of presentation, while only one fourth of them had nodal metastasis. The rate of recurrence increased in cases of primary tumors in advanced stages and the degree of histological differentiation. The 2-year and 5-year OS rates were of 54.5% (18 patients) and 30.3% (10 patients) respectively. Conclusion Primary tumors in advanced stages, histological grade, and presence of nodal metastasis are poor prognostic markers in terms of long-term survival.

Phytochemical analysis and gastroprotective effect of Stellaria media (L.) Vill. methanolic extract on piroxicam-induced gastric ulcer in Wistar rats.

Stellaria media L. has traditionally been used to treat inflammatory and gastrointestinal ailments. This study aimed to phytochemically characterize the S. media extract and explore its anti-ulcer efficacy against piroxicam-induced stomach lesions in Wistar rats. Phytochemical analysis was performed and antioxidant capacity of extract was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. In vivo, piroxicam (30mg/kg) was administered to induce gastric ulceration. Gastro protective effect of S. media extract was observed at 150, 300 and 450mg/kg, respectively. While omeprazole (20mg/kg) was used as a conventional anti-ulcer drug. After oral treatment for 14 days, stomach acidic secretions, ulcerogenic indices, hematological markers and oxidative stress parameters were assessed along with histological examination. The existence of polyphenol contents in S. media extract was confirmed in correlation to a marked DPPH inhibition (IC50 27.94µg/mL). S. media extract resulted in a dose-dependent elevation in gastric pH while a decrease in acid volume, acidity and ulceration. Also, S. media extract administration restored the impaired hematological markers (RBCs, Hb, WBCs and PLTs) and decreased oxidative stress by reducing oxidants (TOS and MDA) while raising antioxidants (TAC and CAT). Furthermore, gastric histological results corroborated the aforementioned findings. Conclusively, S. media could provide a promising protective effect against drug-induced gastric ulceration.

A cancer disparities curriculum in a hematology/oncology fellowship program.

BACKGROUND: After George Floyd's murder in 2020, the Center for Disease Control and Prevention (CDC) called systemic racism a public health crisis. This health crisis is connected to the already-documented racial and socioeconomic disparities in cancer care. Ensuring hematologists and oncologists are aware of these disparities through their medical education can help to address these disparities. METHODS: The authors implemented a healthcare disparities-focused curriculum in a Hematology/Oncology fellowship program during the 2020-2021 academic year at The Ohio State University Hematology/Oncology Fellowship Program. They implemented a pre- and post- survey to evaluate the efficacy of the program. RESULTS: Fifteen fellows completed the pre-curriculum survey and 14 completed the post-survey. Before the curriculum, 12 fellows (80%) noted a "Fair" or "Good" understanding of healthcare disparities, and 6 (40%) had a "Fair" understanding of disparities in clinical trials and access to novel therapies. Fourteen fellows (93.3%) had not previously participated in a research project focused on identifying or overcoming healthcare disparities. After the curriculum, 12 (85%) fellows strongly agreed or agreed that the information presented in the curriculum was useful for training as a hematologist/oncologist. Twelve fellows (85%) noted "Agree" or "Strongly Agree" that the information presented was relevant to their practice. Eleven fellows (92%) noted that they plan to incorporate healthcare disparities into a future research or clinical project. The majority of fellows, 11 (79%) recommended that the fellowship program continue to have a formal health disparities curriculum in the future. DISCUSSION/CONCLUSION: There is utility in incorporating cancer disparities education into a hematology/oncology academic curriculum. We recommend further analysis of such curricula to improve fellowship education and patient outcomes with these interventions.

Location, location, location: A mini-review of CEBPA variants in patients with acute myeloid leukemia.

CEBPA variants are frequently recurring in acute myeloid leukemia (AML). The prognostic significance of CEBPA mutations has recently undergone a major shift in the 5th edition of WHO classification of hematological neoplasms and ELN 2022 classification. Whereas prior iterations did not specify the type of CEBPA mutation, the updated schema specify that only mutations localized to the C-terminal basic zipper (bZIP) domain are considered prognostically favorable. This change is based primarily on three recently published large datasets evaluating the prognostic significance of mutation location in CEBPA mutant AML. Here, we review the evolution of the prognostic classification of CEBPA variants.

Incidence of surgical site infection following open hernioplasty and comparison of infection rate among ventral and groin hernia repairs at a THQ hospital Lahore: a single surgeon experience.

OBJECTIVE: To determine the incidence of surgical site infection following open hernioplasty, and to compare the infection rate among ventral and groin hernia repairs. Method: The retrospective study was conducted from April 2 to November 30, 2021, at the Government Tehsil Headquarter Hospital Sabzazar, Lahore, Pakistan, and comprised data form June 2018 to December 2020 of patients with ventral abdominal and groin hernia. All patients underwent hernioplasty by a single consultant surgeon and were discharged within 2 days of surgery. Surgical-site infections were recorded on follow-up visits up to 30 days of operation, and were compared between ventral and groin hernia cases. Data was analysed using SPSS 22. RESULTS: Of the 218 patients with mean age 37.07±4.94 years, 117(53.67%) were males, 108(49.54%) smokers and 127(58.25%) hypertensive, while 110(50.45%) had ventral abdominal hernia and 108(49.54%) had groin hernias. Mean operative time and mean hospital stay were 56.53±6.20 minutes and 3.06±1.31days, respectively. Mean wound drainage in abdominal hernia cases was 8.99±2.02 days. Surgical site infection incidence following open hernioplasty was 2(0.91%). Infection rate among ventral abdominal and groin hernioplasty were 1(0.90%) and 1(0.92%) (p=0.50). CONCLUSIONS: Incidence of surgical site infection following open hernioplasty showed no significant difference between ventral abdominal and groin hernia repairs.

Effect of iron-fortified jamun leather on the Asunra-induced anemia in Sprague Dawley rats.

Introduction: Micronutrients such as minerals and vitamins are required in a minute quantity but play a pivotal role in the functioning of the body. Therefore, deficiency in one of them can lead to lethal health conditions. Iron deficiency anaemia is one of the most common micronutrient deficiencies across the world and is affecting women and children. Methods: The present study aimed to investigate the anti-anaemic effect of fortified jamun leather on anaemia biomarkers and haematology in anaemic female Sprague Dawley rats. A total of 40 Sprague Dawley rats were used in 4 groups. Iron deficiency anaemia was induced by oral administration of the Asunra drug. The treatments were fed at two dosage levels i.e., 40 and 60% iron-fortified leather. All animals were treated for 60 days and the parameters including biochemical, and histopathology of the kidney and liver were examined. Results: The experiment's findings showed that the group fed with iron-fortified leather (G3) succeeded significantly (P < 0.05) in restoring the serum iron (98.68 ± 2.88 µg/dL), haemoglobin (12.41 ± 0.32 g/dL), ferritin (24.54 ± 1.98 ng/mL) and haematocrit levels (39.30 ± 1.66%) at the end of the 60 days period. Additionally, the treated group's mean values for transferrin and total iron binding capacity were lower than those of the anaemic rats, indicating an improvement in iron levels. The microscopic analysis revealed that treatments had no toxic effects on the kidney and liver tissues, except in the diseased group, which had necrosis and irregular cell structure. Conclusion: Conclusively, iron-fortified jamun leather helped improve iron deficiency biomarkers and imparted a non-toxic effect on tissues in rats.

Phytochemical screening of Prunus avium for its antioxidative and anti-mutagenic potential against DMBA-induced hepatocarcinogenesis.

Scope: Prunus avium fruit is the richer source of phenolics known to exert anticancer and anti-invasive activities. The study aimed at elucidating antiproliferative and chemo-preventive potential of sweet cherries (P. avium) against the in vivo hepatocarcinoma model. Methods and results: The quantification of ultrasound-assisted extract (UAE) of P. avium depicted anthocyanins, ferulic acid, gallic acid, quercetin, syringic acid and p- and m-coumaric acids as major phytochemicals. The hepatocarcinoma (HCC) was induced in rats through intraperitoneal administration of DMBA (20 mg/kg B.W) once a week for the period of eight weeks. The intragastric administration of P. avium UAE, as cotreatment (500 mg/Kg B.W) to treatment group, significantly (p < 0.01) attenuated the raised serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) as well as total oxidative stress (TOS) and enhanced total antioxidant capacity TAOC in contrast to diseased rats. Moreover, microscopic examination of hepatic tissues confirmed the pleomorphism, nests of neoplastic hepatocytes and necrosis in HCC-bearing rats as compared to extract-fed rats, where these necrotic changes were suppressed. Besides, qRT-PCR analysis of hepatic tissues demonstrated the higher mRNA expression of CHEK1, CHEK2 and P21/CDKN1α genes, while downexpression of ATM gene in extract fed rats, further denoting the anti-mutagenic potential. Conclusion: Consequently, the polyphenol-rich sweet cherries UAE exhibited antiproliferative and chemo-preventive potential by reducing tumor biomarkers, serum transaminases and oxidative stress, as well as enhancing antioxidant status. It further upregulated the downstream targets of ATM signaling cascade.

Secretory carcinoma of minor salivary glands of buccal mucosa: A case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Secretory carcinoma (SC) is an uncommon salivary gland neoplasm of the oral cavity that microscopically may mimic acinic cell carcinoma (ACC) and mucoepidermoid carcinoma (MEC). Secretory carcinoma (SC) of the salivary gland has been recently added in fourth edition of the head and neck world health organization. Most of these tumors are located on the parotid gland with very few cases reported in the minor salivary glands of the buccal mucosa. This work has been reported in line with the SCARE criteria. PRESENTATION OF CASE: A 42 years old hypertensive male, shop keeper by occupation, with no prior addiction history, no dental extraction or trauma, presented with complaint of nodular lesion on left buccal mucosa for five years. On Clinical examination, adequate mouth opening, dentulous patient with 2.4 × 2 cm well circumscribed, nodular, non-tender, benign looking lesion was observed on left buccal mucosa near upper alveolus. Overlying mucosa appeared normal with no clinically palpable cervical lymphadenopathy. Histopathology revealed salivary gland neoplasm favoring secretory carcinoma. MRI scan showed lobulated enhancing nodular lesion arising from left buccal mucosa of size 2.3 ∗ 1.3 ∗ 1.7 cm, close to left superior alveolus without involving any cortical areas of marrow infiltration, with bilateral symmetrical level IIa reactive cervical nodes. Wide local excision and ipsilateral selective neck dissection [level 1, 2, 3] was done. Post-operative period was smooth with no complain of paresthesia observed. The final histopathology report showed secretory carcinoma. Two out of six lymph nodes from level I were positive for metastatic carcinoma with no extra nodal extension. Final stage of the tumor was pT1N2bMx. Patient underwent post-operative adjuvant radiotherapy for period of 6 weeks, received total 30 fractions and total dose of 6000 centigray. CLINICAL DISCUSSION: SC behaved clinically an indolent being painless and having long duration of symptoms with normal overlying mucosa. But histopathologically there was cervical node metastasis. That changed final staging and added adjuvant treatment for this patient. The discrepancy in clinical and pathological diagnosis might be due to the indolent clinical behavior of SC arising in the minor salivary gland of buccal mucosa. In the present case, the absence of zymogen granules and presence of microcytic pattern with eosinophilic cytoplasm and eosinophilic secretory material were suggestive of SC. CONCLUSION: This case report represents a rare case of SC of minor salivary glands of buccal mucosa, which was indolent as per clinical presentation but on final histopathological report it had cervical nodal metastasis that changed the final stage of the disease, for which adjuvant radiotherapy was needed. Although Secretory carcinomas are generally considered having a favorable prognosis and are regarded as low- grade carcinomas with limited number of recurrence and cervical nodal metastasis, but sometimes they do metastasize to cervical nodes for which accurate and timely intervention in the form of neck dissection may be performed to establish final staging and start additional treatment modality if required for better outcome of the disease.

Outcomes with chimeric antigen receptor t-cell therapy in relapsed or refractory acute myeloid leukemia: a systematic review and meta-analysis.

Background: We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML). Methods: We performed a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed. Results: We analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I2 =65%) and 65.2% (95% CI 0.36-0.91, I2 =57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I2 =77%), 3.9% (95% CI 0.00-0.19, I2 =22%), and 1.6% (95%CI 0.00-0.21, I2 =33%), respectively. Conclusion: CAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion.