The emerging role of liquid biopsy in oral squamous cell carcinoma detection: advantages and challenges.

INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC), the sixth most widespread malignancy in the world, accounts for 90% of all cases of oral cancer. The primary risk factors are tobacco chewing, alcohol consumption, viral infection, and genetic modifications. OSCC has a high morbidity rate due to the lack of early diagnostic methods. Nowadays, liquid biopsy plays a vital role in the initial diagnosis of oral cancer. ctNAs extracted from saliva and serum/plasma offer meaningful insights into tumor genetics and dynamics. The interplay of these elements in saliva and serum/plasma showcases their significance in advancing noninvasive, effective OSCC detection and monitoring. AREAS COVERED: This review mainly focused on the role of liquid biopsy as an emerging point in the diagnosis and prognosis of OSCC and the current advancements and challenges associated with liquid biopsy. EXPERT OPINION: Liquid biopsy is regarded as a new, minimally invasive, real-time monitoring tool for cancer diagnosis and prognosis. Many biomolecules found in bodily fluids, including ctDNA, ctRNA, CTCs, and EVs, are significant biomarkers to identify cancer in its early stages. Despite these groundbreaking strides, challenges persist. Standardization of sample collection, isolation, processing, and detection methods is imperative for ensuring result reproducibility across diverse studies.

Comprehensive DNA methylation profiling by MeDIP-NGS identifies potential genes and pathways for epithelial ovarian cancer.

Ovarian cancer, among all gynecologic malignancies, exhibits the highest incidence and mortality rate, primarily because it is often presents with non-specific or no symptoms during its early stages. For the advancement of Ovarian Cancer Diagnosis, it is crucial to identify the potential molecular signatures that could significantly differentiate between healthy and ovarian cancerous tissues and can be used further as a diagnostic biomarker for detecting ovarian cancer. In this study, we investigated the genome-wide methylation patterns in ovarian cancer patients using Methylated DNA Immunoprecipitation (MeDIP-Seq) followed by NGS. Identified differentially methylated regions (DMRs) were further validated by targeted bisulfite sequencing for CpG site-specific methylation profiles. Furthermore, expression validation of six genes by Quantitative Reverse Transcriptase-PCR was also performed. Out of total 120 differentially methylated genes (DMGs), 68 genes were hypermethylated, and 52 were hypomethylated in their promoter region. After analysis, we identified the top 6 hub genes, namely POLR3B, PLXND1, GIGYF2, STK4, BMP2 and CRKL. Interestingly we observed Non-CpG site methylation in the case of POLR3B and CRKL which was statistically significant in discriminating ovarian cancer samples from normal controls. The most significant pathways identified were focal adhesion, the MAPK signaling pathway, and the Ras signaling pathway. Expression analysis of hypermethylated genes was correlated with the downregulation of the genes. POLR3B and GIGYF2 turned out to be the novel genes associated with the carcinogenesis of EOC. Our study demonstrated that methylation profiling through MeDIP-sequencing has effectively identified six potential hub genes and pathways that might exacerbate our understanding of underlying molecular mechanisms of ovarian carcinogenesis.

Unraveling the Genetic Web: H-Ras Expression and Mutation in Oral Squamous Cell Carcinoma-A Systematic Review.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a commonly occurring malignancy with complex genetic alterations contributing to its development. The H-Ras, a proto-oncogene, becomes an oncogene when mutated and has been implicated in various cancers. This systematic review aims to research to what extent H-Ras expression and mutation contribute to the development and progression of OSCC, and how does this molecular alteration impacts the clinical characteristics and prognosis in patients with OSCC. METHODS: A thorough electronic scientific literature search was carried out in PUBMED, SCOPUS, and GOOGLE SCHOLAR databases from 2007 to 2021. The search strategy yielded 120 articles. Following aggregation and filtering all results through our inclusion and exclusion criteria total 9 articles were included in our literature review. It has also been registered with PROSPERO (CRD42023485202). RESULTS: It was found that mutations in the Ras gene commonly reported in hotspots at codons 12, 13, and 61 resulting in the activation of downstream signaling pathways causing abnormal and uncontrolled cell growth. This systematic review has shown an increased prevalence of H-Ras mutation in well-differentiated OSCC and also the prevalence of H-Ras mutation in individuals engaging in multiple risk behaviors, particularly chewing tobacco, demonstrated a significant association with a higher prevalence of H-Ras positivity. CONCLUSION: This review sheds light on the prevalence of H-Ras mutations, their association with clinical characteristics, and their potential implications for OSCC prognosis. It also enhances our comprehension of the molecular mechanisms that underlie OSCC and paves the way for further research into targeted treatments based on H-Ras alterations.

Pediatric Ventilator-Associated Events Before and After a Multicenter Quality Improvement Initiative.

Importance: Pediatric ventilator-associated events (PedVAEs, defined as a sustained worsening in oxygenation after a baseline period of stability or improvement) are useful for surveillance of complications from mechanical ventilation. It is unclear whether interventions to mitigate known risk factors can reduce PedVAE rates. Objective: To assess whether adherence to 1 or more test factors in a quality improvement bundle was associated with a reduction in PedVAE rates. Design, Setting, and Participants: This multicenter quality improvement study obtained data from 2017 to 2020 for patients who were mechanically ventilated and cared for in neonatal, pediatric, and cardiac intensive care units (ICUs). These ICUs were located in 95 hospitals participating in the Children's Hospitals' Solutions for Patient Safety (SPS) network in North America. Data analyses were performed between September 2021 and April 2023. Intervention: A quality improvement bundle consisted of 3 test factors: multidisciplinary apparent cause analysis, daily discussion of extubation readiness, and daily discussion of fluid balance goals. This bundle was distributed to a subgroup of hospitals that volunteered to participate in a collaborative PedVAE prevention initiative under the SPS network guidance in July 2018. Main Outcomes and Measures: Each SPS network hospital submitted monthly PedVAE rates from January 1, 2017, to May 31, 2020, and test factor data were submitted from July 1, 2018, to May 31, 2020. Analyses focused on hospitals that reliably submitted PedVAE rate data, defined as outcomes data submission through May 31, 2020, for at least 80% of the baseline and postbaseline periods. Results: Of the 95 hospitals in the SPS network that reported PedVAE data, 21 were grouped in the Pioneer cohort and 74 in the non-Pioneer cohort. Only 12 hospitals (57%) from the 21 Pioneer hospitals and 33 (45%) from the 74 non-Pioneer hospitals were considered to be reliable reporters of outcome data. Among the 12 hospitals, the PedVAE rate decreased from 1.9 to 1.4 events per 1000 ventilator days (absolute rate difference, -0.6; 95% CI, -0.5 to -0.7; P < .001). No significant change in the PedVAE rate was seen among the 33 hospitals that reliably submitted PedVAE rates but did not implement the bundle. Of the 12 hospitals, 3 that reliably performed daily discussion of extubation readiness had a decrease in PedVAE rate from 2.6 to 1.2 events per 1000 ventilator days (absolute rate difference, -1.4; 95% CI, -1.0 to -1.7; P < .001), whereas the other 9 hospitals that did not implement this discussion did not have a decrease. Conclusions and Relevance: This study found that a multicenter quality improvement intervention targeting PedVAE risk factors was associated with a substantial reduction in the rate of PedVAEs in hospital ICUs. The findings suggest that ICU teams seeking to reduce PedVAEs incorporate daily discussion of extubation readiness during morning rounds.

Evaluation of HER2Neu Status in Periampullary Cancers in Tertiary Care Centre in Northern India: A Three-Year Retrospective Study.

Background Periampullary carcinoma is a heterogeneous group of malignancies, and despite advances in treatment, its mortality rate remains high. A better understanding of the disease and factors influencing its course and potential therapeutic targets is imperative for improving its overall outcome. Through comprehensive cytogenetic analysis, it has been established that the development of periampullary carcinogenesis involves specific chromosomal aberrations, dysregulation of oncogenes, and suppression of genes in a multistep progressive manner. Our study aimed to evaluate the expression of human epidermal growth factor (HER2Neu) in periampullary cancers using immunohistochemistry and fluorescent in situ hybridization. Material and methods This was a retrospective study in which all consecutive cases of periampullary carcinoma diagnosed over a period of three years were evaluated. HER2neu expression was analyzed using immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH). Histopathological evaluation was performed according to the College of American Pathologists (CAP) protocol. Results Twenty patients were diagnosed during the study period. On histomorphologic analysis, most cases (n=17) were diagnosed as well-differentiated adenocarcinomas, the most common subsite being the ampulla of Vater and pathological staging as pT2N0Mx. On IHC, no overexpression of HER2Neu was reported in any case, but FISH analysis revealed one point of amplification with HER/centromere enumerator probe (CEP) ratio>2. Conclusion HER2Neu evaluation in periampullary carcinoma has limited value; thus, it could have a restricted therapeutic role.

Genome-wide expression profiling reveals novel biomarkers in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most aggressive and frequent malignancy detected among women worldwide. The pathophysiology of OC should, therefore be better understood to identify diagnostic, prognostic, and predictive novel biomarkers necessary for early detection, management, and prognostication. In this study, we aimed to investigate transcriptomic landscape and biomarker through RNA-seq data analysis. Further analysis by Protein Protein network identified top 10 Differentially Expressed Genes (DEGs). KEGG pathway enrichment analysis revealed the significant enrichment of DEGs in basal cell carcinoma, cell cycle and FoxO signalling pathway. The RNA-seq results of 10 DEGs were validated by QRT-PCR and TCGA database. Correlation studies were also performed between gene expression and clinical characteristics followed by survival analysis. Finally, 8 DEGs (CDKN1A, BCL6, CDC45, WNT2, TLR5, AQP5) including two novel DEGs (CSN1S1 and NKILA) were identified showing significant correlations with EOC characteristics. These may serve as interesting biomarkers and novel treatment targets and warrant further investigation into the functional outcome of EOC.

Effect of preoperative ibuprofen on pain after lower third molar removal: A randomized controlled trial.

Aim: The aim of the study is to predict the effect of preemptive analgesics in the third molar surgery and to analyze whether the number and frequency of postoperative analgesics are reduced following the administration of preemptive analgesics. Materials and Methods: The present study was carried out on 50 patients who reported to the Department of Oral and Maxillofacial Surgery for removal of their impacted mandibular third molar. The patients were randomly divided into two groups of 25 patients each - Group A (test group) patients receiving ibuprofen (400 mg) half an hour before the surgery and placebo half an hour after surgery and the Group B (control group) patients receiving placebo half an hour before the surgery and ibuprofen (400 mg) half an hour after surgery. Both groups of patients will be instructed to avoid any drug but those prescribed (ibuprofen 400 mg SOS and rescue medication of tramadol 50 mg SOS) and not to seek any medical help elsewhere for postoperative problems. The pain was recorded using a visual analog scale. Results: Demographic data in the study show females (8%) and male (92%) patients. The average time taken for surgery was more in the control group (58.36 min) as compared to the test group (55.64 min) with no statistically significant difference. Values of pain score, medication score, number of rescue medication, and frequency at different time intervals (at baseline, after 3 h, 6 h, 24 h, and 7 days) are expressed in terms of mean and standard deviation, respectively, and the result shows the statistically significant difference for pain score at baseline and 7th-day time interval only. The distribution of different types of impaction and different types of elevation/odontotomy shows a significant association in test and control groups. Conclusion: Preoperative ibuprofen decreases the frequency and intensity of the pain. We believe that since this preoperative ibuprofen seems to be beneficial without any adverse effects, it may be used routinely in the 3rd molar surgeries and even in routine extraction.

BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer.

Background & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George's Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (≥3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of "BRCAness" in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP-ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.

Intratumoral Microbiota Changes with Tumor Stage and Influences the Immune Signature of Oral Squamous Cell Carcinoma.

Characterization of the oral microbiota profile through various studies has shown an association between the microbiome and oral cancer; however, stage-specific determinants of dynamic changes in microbial communities of oral cancer remain elusive. Additionally, the influence of the intratumoral microbiota on the intratumoral immune system remains largely unexplored. Therefore, this study aims to stratify microbial abundance in the early-onset and subsequent stages of oral cancer and analyze their influence on clinical-pathological and immunological features. The microbiome composition of tissue biopsy samples was identified using 16S rRNA amplicon sequencing, while intratumoral and systemic immune profiling was done with flow cytometry and immunohistochemistry-based analysis. The bacterial composition differed significantly among precancer, early cancer, and late cancer stages with the enrichment of genera Capnocytophaga, Fusobacterium, and Treponema in the cancer group, while Streptococcus and Rothia were enriched in the precancer group. Late cancer stages were significantly associated with Capnocytophaga with high predicting accuracy, while Fusobacterium was associated with early stages of cancer. A dense intermicrobial and microbiome-immune network was observed in the precancer group. At the cellular level, intratumoral immune cell infiltration of B cells and T cells (CD4+ and CD8+) was observed with enrichment of the effector memory phenotype. Naive and effector subsets of tumor-infiltrating lymphocytes (TILs) and related gene expression were found to be distinctly associated with bacterial communities; most importantly, highly abundant bacterial genera of the tumor microenvironment were either negatively correlated or not associated with the effector lymphocytes, which led to the conclusion that the tumor microenvironment favors an immunosuppressive and nonimmunogenic microbiota. IMPORTANCE The gut microbiome has been explored extensively for its importance in the modulation of systemic inflammation and immune response; in contrast, the intratumoral microbiome is less studied for its influence on immunity in cancer. Given the established correlation between intratumoral lymphocyte infiltration and patient survival in cases of solid tumors, it was pertinent to explore the extrinsic factor influencing immune cell infiltration in the tumor. Modulation of intratumoral microbiota could have a beneficial effect on the antitumor immune response. This study stratifies the microbial profile of oral squamous cell carcinoma starting from precancer to late-stage cancer and provides evidence for their immunomodulatory role in the tumor microenvironment. Our results suggest combining microbiome study with immunological signatures of tumors for their prognostic and diagnostic application.

Diagnostics and Therapeutic Potential of miR-205 and miR-34a in Ovarian Cancer Management: A miRNA-Target-Based Analysis.

Epithelial ovarian cancer (EOC) treatment strategies mainly focused on surgery combined with chemotherapy. Recent targeted therapy techniques emerge as milestone and could be used for management of ovarian cancer (OC) progression with more efficacy. The aim is to evaluate the therapeutic and diagnostic potential of microRNA (miRNA) in management of EOC using in silico and quantitative real-time PCR (qRT-PCR) expression analysis. We performed functional enrichment and miRNA-Target genes expression analysis in 48 EOC and 22 normal tissue samples using qRT-PCR and correlated with miRNA expression data in matched samples to evaluate the diagnostic and therapeutic potential of miRNA in OC management. In silico functional enrichment analysis revealed miRNA association with disease. Target genes of miRNAs participate in several biologically important pathways leading to cancer progression. Targets of miRNA-205 and miRNA-34a were significantly downregulated, and upregulated, respectively, in EOC. Moreover, significant negative correlation between relative expression of miRNA-205 and target genes (BCL2, ZEB1, E2F1, and TP53) was observed with r = -0.813; r = -0.755; r = -0.559; and r = -0.767, respectively. Similarly, miRNA-34a also showed higher negative correlation with target genes (MDM4, MAPK3, BRCA1, AREG) with r = -0.840; r = -0.870; r = -0.622; and r = -0.623, respectively. In addition, receiver operating characteristics analysis of combined miRNA panel, miRNA-205-Target gene panel, and miRNA-34a-Target gene panel exhibited higher diagnostics value with area under the curve (AUC) of 92.7 (p < 0.0001), 94.8 (p < 0.0001), and 98.3 (p < 0.0001), respectively. Negative Correlation between miRNA and target genes expression data in matched samples highlights therapeutic potential of miRNA in EOC management. Moreover, combined diagnostic potential of miRNA-target gene panel could predict risk of EOC with higher AUC, sensitivity, and specificity.

Immunohistochemical appraisal of epithelial mesenchymal transition type III in gall bladder cancer.

Background: Epithelial-mesenchymal transition (EMT) is the heart of invasion. EMT associated with cancer progression and metastasis is known as type III EMT. Beta-catenin, E-cadherin, and MMP9 markers of EMT are routinely employed for diagnostic purposes. Aims: We employed these markers to study EMT by immunohistochemistry (IHC) in gall bladder cancer (GBC) with respect to depth of tumor invasion, clinical outcome, and disease-free survival. Settings and Design: This was a prospective case-control study. Material and Methods: Seventy gall bladders were included (50 GBC and 20 CC). After detailed histology, immunoexpression was studied in terms of percentage and strength of expression. Statistics Analysis Used: Expression was compared between CC and GBC by Student t test and analysis of variance. Kaplan-Meier was used for survival analysis, and the extent of agreement ("Kappa") was calculated. Results and Conclusions: The age of incidence of GBC was 49.40 (+11.6) years with female predominance (F:M = 4:1). In 88% (44/50) of GBC, the fundus was involved. Moderately differentiated adenocarcinoma was most frequent [54%; 27/50]. Significant downregulation of E-cadherin (P = 0.022) and beta-catenin (P < 0.001) and upregulation in MMP9 (P < 0.001) were seen in GBC with respect to CC with significant association among them. MMP9 expression was significantly associated with higher tumor stage but with chemotherapeutic response. Our results display that epithelial-mesenchymal transition type III plays a role in GBC invasion. MMP9 overexpression and loss of membranous beta-catenin may be considered a marker for poor clinical outcomes and advanced disease.

Management of adult renal trauma: a practice management guideline from the eastern association for the surgery of trauma.

BACKGROUND: The kidney is the most frequently injured component of the genitourinary system, accounting for 5% of all trauma cases. Several guidelines by different societies address the management of urological trauma. However, unanswered questions remain regarding optimal use of angioembolization in hemodynamically stable patients, indications for operative exploration of stable retroperitoneal hematomas and renal salvage techniques in the setting of hemodynamic instability, and imaging practices for patients undergoing non-operative management. We performed a systematic review, meta-analysis, and developed evidence-based recommendations to answer these questions in both blunt and penetrating renal trauma. METHODS: The working group formulated four population, intervention, comparator, outcome (PICO) questions regarding the following topics: (1) angioembolization (AE) usage in hemodynamically stable patients with evidence of ongoing bleeding; (2) surgical approach to stable zone II hematomas (exploration vs. no exploration) in hemodynamically unstable patients and (3) surgical technique (nephrectomy vs. kidney preservation) for expanding zone II hematomas in hemodynamically unstable patients; (4) frequency of repeat imaging (routine or symptom based) in high-grade traumatic renal injuries. A systematic review and meta-analysis of currently available evidence was performed. RevMan 5 (Cochran Collaboration) and GRADEpro (Grade Working Group) software were used. Recommendations were voted on by working group members and concurrence was obtained for each final recommendation. RESULTS: A total of 20 articles were identified and analyzed. Two prospective studies were encountered; the majority were retrospective, single-institution studies. Not all outcomes projected by PICO questions were reported in all studies. Meta-analysis was performed for all PICO questions except PICO 3 secondary to the discrepant patient populations included in those studies. PICO 1 had the greatest number of articles included in the meta-analysis with nine studies; yet, due to differences in study design, no critical outcomes emerged; similar differences among a smaller set of articles prevented observation of critical outcomes for PICO 4. Analyses of PICOs 2 and 3 favored a non-invasive or minimally invasive approach in-line with current international practice trends. CONCLUSION: In hemodynamically stable adult patients with clinical or radiographic evidence of ongoing bleeding, no recommendation could be made regarding the role of AE vs. observation. In hemodynamically unstable adult patients, we conditionally recommend no renal exploration vs. renal exploration in stable zone II hematomas. In hemodynamically unstable adult patients, we conditionally recommend kidney preserving techniques vs. nephrectomy in expanding zone II hematomas. No recommendation could be made for the optimal timing of repeat imaging in high grade renal injury. LEVEL OF EVIDENCE: Guideline; systematic review, level III.

Cutaneous Surgical Wounds Have Distinct Microbiomes from Intact Skin.

Infections are relatively rare following cutaneous surgical procedures, despite the potential for wound exposure to pathogens both during surgery and throughout the healing process. Although gut commensals are believed to reduce the risk of intestinal infections, an analogous role for skin commensals has not been described. In fact, the microbiome of normally healing surgical skin wounds has not yet been profiled using culture-independent techniques. We characterized the wound microbiome in 53 patients who underwent skin cancer surgery and healed without signs or symptoms of infection. A week after surgery, several bacterial species displayed significant differences in relative abundance when compared to control, nonoperated skin from the same patient. The relative abundance of the most common bacterium found on intact skin, Cutibacterium acnes, was reduced in wounds 5-fold. Staphylococcus aureus, a frequent cause of postoperative skin infections, was enriched 6.4-fold in clinically noninfected wounds, suggesting active suppression of pathogenicity. Finally, members of the Corynebacterium genus were the dominant organism in postoperative wounds, making up 37% of the average wound microbiome. The enrichment of these bacteria in normally healing wounds suggests that they might be capable of providing colonization resistance. Future studies focused on the biological and clinical significance of the wound microbiome may shed light on normal wound healing and potential therapeutic opportunities to mitigate infection risk. IMPORTANCE Commensal bacteria on skin may limit the ability of pathogenic bacteria to cause clinically significant infections. The bacteria on healing acute wounds, which might provide such a protective effect, have not been described using culture-independent approaches in the absence of antibiotics. We compare the microbiome of wounds a week after skin cancer removal surgery with intact skin from the same patient. We find that the potentially pathogenic species S. aureus is common on these healing wounds despite the absence of symptoms or signs of infection. We report that bacteria often considered as potential skin probiotics, including Staphylococcus epidermidis, do not reach high relative abundance in wound microbiomes. In contrast, specific members of the Corynebacterium genus, rarely associated with infections, were significantly enriched in healing wounds compared to intact skin. Future work is needed to see if Corynebacterium species or derivatives thereof could be employed to lower the risk of wound infection.

Trauma center variation of head computed tomography utilization in children presenting with mild traumatic brain injury.

BACKGROUND: Although published clinical decision rules have identified indications for the use of head CT in children with mild traumatic brain injury, practices vary. OBJECTIVE: This study seeks to evaluate whether the utilization of head CT in pediatric trauma patients presenting with mTBI varies between American College of Surgeons verified pediatric trauma centers (ACS-PTC) and adult-only trauma centers (ACS-AOTC). MATERIAL AND METHODS: A retrospective cohort study of 24,104 trauma patients, ≤17, who presented to the emergency department at 337 ACS verified level I/II trauma centers with isolated mTBI was conducted using National Trauma Data Bank records (2011-2015). Multivariable logistic regression was used to compare the odds of a patient receiving a head CT when treated at an ACS-PTC vs. an ACS-AOTC, controlling for demographic, injury, and hospital-level confounders. Effect modification by loss of consciousness was assessed and adjusted head CT odds were recalculated in patients stratified by LOC status. RESULTS: There was no significant difference in the adjusted odds of receiving a head CT at an ACS-PTC vs. an ACS-AOTC (odds ratio: 0.98, 95% confidence interval: 0.92-1.04). However, in patients who had a LOC, the adjusted OR of receiving a head CT at an ACS-PTC vs ACS-AOTC was 0.71 (95% confidence interval: 0.65-0.78). CONCLUSION: Children presenting to the emergency department of an ACS-verified level I or II trauma center with mTBI who had a loss of consciousness are less likely to receive a head CT at an ACS verified pediatric trauma center than at an ACS verified adult-only trauma center.

Case Report: WATCHMAN Procedure Complicated By Atrial Perforation and Device Dislodgement.

Atrial perforation and device dislodgment are uncommon encounters after percutaneous left atrial appendage exclusion procedures. The literature describes how various endovascular and surgical approaches can be applied to treat these complications. In this case report, we describe an atrial perforation that occurred after a WATCHMAN™ FLX device (Boston Scientific) deployment. Heart manipulation with lifting was required for the atrial repair. During this maneuver, the device dislodged and was managed by surgical device extraction and left atrial appendage resection and suture closure. Minimal to no manipulation of the left atrium during surgical exploration was found to be invaluable in order to avoid device dislodgement and additional surgical corrective interventions. Additionally, intraoperative transesophageal echocardiography at the beginning and conclusion of the case is key in monitoring the device position and identifying device dislodgement.

New Insights into Melanoma Tumor Syndromes.

Melanoma tumor syndromes (MTS) represent an important minority of familial melanoma cases. In these patients, the accumulation of sequence alterations in essential genes may prelude the risk of internal malignancies, in addition to melanoma. Although several host and environmental factors have been implicated in familial melanoma, the exact mechanisms of cancer predisposition-particularly in the context of mixed cancer syndromes-still remain unclear. In this paper, we review new insights into MTS and elucidate recent efforts that guide individualized prognostication and treatment for these diseases in the past quarter century.

Quality of Life in Patients with Recurrent Oral Squamous Cell Carcinoma: A Study from India.

Background: Locoregional recurrence of oral cancer causes significant morbidity. This study aims at assessing the functional outcomes of patients undergoing treatment for recurrent oral squamous cell carcinoma. Methods: This study was done in a tertiary care center in North India and includes prospective cohort of 179 recurrent oral carcinoma patients, from September 2017 to September 2018. Patients undergoing treatment of recurrent oral carcinoma were assessed for quality-of-life score at baseline before starting treatment and two months after the completion of the treatment. For the assessment, EORTC QLQH&N35 questionnaire was used. Results: Of 179 patients included, 71 (39.66%) patients underwent salvage surgery and 104 patients (58.10%) received palliative chemotherapy. One hundred and thirty patients could complete the "EORTC-QOL-H&N-35" questionnaire on required two occasions. Forty-nine patients died before completing second questionnaire. More than half (55.6%) of patients who underwent salvage surgery had improved quality of life after the procedures. They have little or no pain in oral cavity, improved swallowing, less odynophagia, improvement in neck and shoulder pain, less problems with the external appearance and socialization, and enjoyed better sexual life. In patients receiving palliative chemotherapy, the quality of life declined in majority (88.1%) of the patients. Conclusions: Although salvage surgery is the best modality of treatment for recurrent oral carcinoma, only about one-third of patients qualify for surgery and enjoy improved quality of life following surgery. On the other hand, in majority of the patients receiving palliative chemotherapy, the quality of life worsened with time and treatment.

Expression of aldehyde dehydrogenase 1A1 in oral squamous cell carcinoma and its correlation with clinicopathological parameters.

Background: Aldehyde dehydrogenase 1A1 (ALDH1A1) is a key aldehyde dehydrogenase (ALDH) isozyme, related to the cancer stem cells which are responsible for initiating tumor growth, progression, and recurrence. High expression of ALDH1A1 has been reported in several tumor types in humans and its expression is associated with poor prognosis. The aim of this study was to assess the expression of the ALDH1A1 in oral squamous cell carcinoma (SCC) and its correlation with various clinicopathological parameters. Materials and Methods: ALDH1A1 expression was analyzed by using immunohistochemistry on paraffin blocks of 112 cases of primary oral SCC and their corresponding 68 lymph nodes with metastatic deposits. ALDH1A1 expression was also correlated with various clinicopathological parameters. Statistical analysis was done with statistical analysis software, the Statistical Package for the Social Sciences version 21.0. Results: High ALDH1A1 expression was observed in 31.2% of cases of primary oral SCC as compared to 73.5% in lymph node metastasis. A statistically significant difference (P = 0.04) was observed in high TNM stages (68.6%) of the tumor as compared to low TNM stages (31.4%). However, histopathological grades of tumor showed nonsignificant correlation with ALDH1A1 expression (P = 0.093). 40.2% of patients were expired at the end of the study, and the rate of mortality was significantly higher (P = 0.01) in patients with high ALDH1A1 expression as compared to low expression (60.0% vs. 31.2%). Conclusion: High ALDH1A1 expression was associated with higher TNM tumor stage and high nodal stage. It was also associated with high mortality rate which validates it as a marker of invasiveness and poor prognosis in oral SCC.

Current status and barriers in pulmonary hypertension care delivery in India: A qualitative analysis.

Although pulmonary hypertension (PH) is widely prevalent in India, care delivery for this condition has unique challenges in a lower middle-income country (LMIC). To describe care delivery for patients with PH and associated barriers in India. We interviewed physicians across eight healthcare systems in India about PH clinical care using semi-structured enquiries to understand care delivery and associated challenges in their specific practice as well as the associated health system. Qualitative analysis was performed using content analysis methodology. Physicians reported that common causes for PH in their practice were rheumatic mitral valve disease, coronary artery disease, and congenital heart disease (CHD). No center had a dedicated PH program. Only one center had a specific protocol for PH management. Diagnostic evaluations were limited, and right heart catheterizations were recommended for patients with CHD. Pulmonary vasodilator therapy was used for severe symptoms or markers of severe disease. Agents used to treat PH were widely variable across physicians and prostacyclins are unavailable in India. Barriers included limited training in PH for physicians, lack of consensus guidelines for PH specific to LMIC, and lack of financial incentives for health care systems to organize dedicated PH programs. Other barriers included poor patient health literacy and socioeconomic barriers that limit ability to test and treat PH. PH care delivery in India is variable with widely differing clinical practices. Dedicated training in PH management and establishing guidelines specific to LMIC like India can form the first step forward.