Malignant Etiology Research Articles

Implementing 18F-DCFPyL PET in clinical practice: Prescribing patterns and utilization at a large academic center.

42 Background: 18F-DCFPyL imaging was recently approved for initial staging in patients (pts) with prostate cancer and suspected metastasis and for those with biochemical recurrence (BCR). 18F-DCFPyL recently became available at our NCI-Designated Comprehensive Cancer Center comprising 6 teaching hospitals and 2 outpatient facilities. As real-world data on 18F-DCFPyL usage in the US are lacking, our objective was to describe prescription patterns and utilization for 18F-DCFPyL. Methods: We identified 18F-DCFPyL scans performed at our center from 1/1/2022-5/10/2022 and abstracted corresponding clinical data through electronic medical record (EMR) review. Demographic, laboratory, pathological and clinical data and provider-level usage were characterized by review of the EMR and, if necessary and feasible, provider interview. Results: There were 164 18F-DCFPyL scans performed across the study period for 164 unique pts (median age 70 years, 73.8% White, 20.1% Black). Ordering providers belonged to Medical Oncology (54.3%), Radiation Oncology (42.7%), Urology (2.4%), and Nuclear Medicine (1%). The majority of scans were ordered for isolated PSA rise (n=93, 56.7%) and initial staging (n=26, 15.9%), in concordance with FDA-approved indications. Nevertheless, many scans were ordered for alternate indications. Restaging of pts with known refractory or metastatic disease (11.0%), PSA persistence after definitive therapy (8.5%), and PSA rises below the threshold of BCR (4.9%) were common alternate rationales for imaging. A minority of scans had a secondary indication such as RT field planning, distinguishing between two primary cancers, PSA persistence in high-risk disease, possible radioisotope therapy, and, most frequently, clarification of lesions seen on conventional imaging (n = 7). 22 pts were on androgen-deprivation (ADT, n=17) or anti-androgens (AR, n=11) when receiving PSMA imaging, with 5 pts on both; the median testosterone at time of imaging was <20 ng/dL. Indeterminate lesions, defined as tracer avid with uncertain malignant status, were most often found in lymph nodes (n = 22) and focal rib lesions (n = 17), of which 12 were solitary, 3 were multifocal and 2 were superimposed on fractures. Conclusions: Shortly after adoption at a large cancer center, 18F-DCFPyL has been prescribed in various clinical settings outside of FDA approvals. Around 1/8 were performed with pts on ADT/AR, with testosterone at castrate levels. Findings of uncertain malignant etiology included solitary (7%) and multifocal (2%) rib lesions. These data reveal substantial variability in usage and areas of uncertainty in the interpretation of 18F-DCFPyL imaging in real-world clinical settings, underlining the need for further studies on its potential usefulness in expanded indications.

Polymorphisms in DNA Repair Genes and Association with Rheumatoid Arthritis in a Pilot Study on a Central European Population.

Rheumatoid arthritis (RA) is a chronic, multifactorial autoimmune disease characterized by chronic arthritis, a tendency to develop joint deformities, and involvement of extra-articular tissues. The risk of malignant neoplasms among patients with RA is the subject of ongoing research due to the autoimmune pathogenesis that underlies RA, the common etiology of rheumatic disease and malignancies, and the use of immunomodulatory therapy, which can alter immune system function and thus increase the risk of malignant neoplasms. This risk can also be increased by impaired DNA repair efficiency in individuals with RA, as reported in our recent study. Impaired DNA repair may reflect the variability in the genes that encode DNA repair proteins. The aim of our study was to evaluate the genetic variation in RA within the genes of the DNA damage repair system through base excision repair (BER), nucleotide excision repair (NER), and the double strand break repair system by homologous recombination (HR) and non-homologous end joining (NHEJ). We genotyped a total of 28 polymorphisms in 19 genes encoding DNA repair-related proteins in 100 age- and sex-matched RA patients and healthy subjects from Central Europe (Poland). Polymorphism genotypes were determined using the Taq-man SNP Genotyping Assay. We found an association between the RA occurrence and rs25487/XRCC1, rs7180135/RAD51, rs1801321/RAD51, rs963917/RAD51B, rs963918/RAD51B, rs2735383/NBS1, rs132774/XRCC6, rs207906/XRCC5, and rs861539/XRCC3 polymorphisms. Our results suggest that polymorphisms of DNA damage repair genes may play a role in RA pathogenesis and may be considered as potential markers of RA.

ROLE OF ULTRASOUND TO DIFFERENTIATE BETWEEN BENIGN AND MALIGNANT THYROID NODULES WITH HISTOPATHOLOGICAL CORRELATION

Background: The only endocrine gland that may be directly examined because to its supercial placement and size is the thyroid gland, which is the largest of all endocrine glands. High resolution real-time gray-scale sonography with the thyroid gland's supercial position enables good visibility and assessment of both its pathologic status and normal structure. The goal was to l Aim: ink histopathology results with sonographic criteria to distinguish between benign and malignant thyroid nodules. From April 2022 to November 2 Materials and Methods: 022, based on criteria for inclusion and exclusion, 50 cases with thyroid nodules were included in the study. Each nodule's sonographic features were identied. After that, the outcomes were contrasted with histopathological diagnosis. 40 Results: benign and 10 malignant solitary thyroid nodules assessed by ultrasound out of 50 total cases were determined, 43 out of 50 instances were benign and 7 were malignant, according to histopathological analysis. To distinguish between benign and malignant etiologies, ultrasound is a relatively safe and accurate investigation with sensitivity of 85.7 % and specicity of 90.7%. In order to distinguish between benign and malignant lesions, USG has proven to possess greater sensitivity. Conclusion: Thyroid nodules were prevalent in women between the ages of 31 and 45. With a sensitivity of 85.7% and a specicity of 90.7%, ultrasound is a relatively safe and accurate test to distinguish between benign and malignant etiologies.

Development and Validation of a Deep Learning Algorithm to Differentiate Colon Carcinoma From Acute Diverticulitis in Computed Tomography Images

Differentiating between malignant and benign etiology in large-bowel wall thickening on computed tomography (CT) images can be a challenging task. Artificial intelligence (AI) support systems can improve the diagnostic accuracy of radiologists, as shown for a variety of imaging tasks. Improvements in diagnostic performance, in particular the reduction of false-negative findings, may be useful in patient care. To develop and evaluate a deep learning algorithm able to differentiate colon carcinoma (CC) and acute diverticulitis (AD) on CT images and analyze the impact of the AI-support system in a reader study. In this diagnostic study, patients who underwent surgery between July 1, 2005, and October 1, 2020, for CC or AD were included. Three-dimensional (3-D) bounding boxes including the diseased bowel segment and surrounding mesentery were manually delineated and used to develop a 3-D convolutional neural network (CNN). A reader study with 10 observers of different experience levels was conducted. Readers were asked to classify the testing cohort under reading room conditions, first without and then with algorithmic support. To evaluate the diagnostic performance, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for all readers and reader groups with and without AI support. Metrics were compared using the McNemar test and relative and absolute predictive value comparisons. A total of 585 patients (AD: n = 267, CC: n = 318; mean [SD] age, 63.2 [13.4] years; 341 men [58.3%]) were included. The 3-D CNN reached a sensitivity of 83.3% (95% CI, 70.0%-96.6%) and specificity of 86.6% (95% CI, 74.5%-98.8%) for the test set, compared with the mean reader sensitivity of 77.6% (95% CI, 72.9%-82.3%) and specificity of 81.6% (95% CI, 77.2%-86.1%). The combined group of readers improved significantly with AI support from a sensitivity of 77.6% to 85.6% (95% CI, 81.3%-89.3%; P < .001) and a specificity of 81.6% to 91.3% (95% CI, 88.1%-94.5%; P < .001). Artificial intelligence support significantly reduced the number of false-negative and false-positive findings (NPV from 78.5% to 86.4% and PPV from 80.9% to 90.8%; P < .001). The findings of this study suggest that a deep learning model able to distinguish CC and AD in CT images as a support system may significantly improve the diagnostic performance of radiologists, which may improve patient care.

Spontaneous transient size reduction of a solitary pulmonary metastasis from a leiomyosarcoma

BackgroundA solitary pulmonary nodule (SPN) poses a diagnostic challenge, which includes both a benign and malignant etiology. A size enlargement often indicates malignancy. We herein describe a case of a solitary pulmonary metastasis from a leiomyosarcoma that regressed transiently during follow-up.Case presentationA 47-year-old woman presented with an SPN detected by follow-up computed tomography 7 years after surgery for a left forearm high-grade leiomyosarcoma. The nodule regressed spontaneously after an additional 6 months, and therefore, an inflammatory change was the most likely diagnosis at that time. However, the nodule enlarged again over the next 5 years. The growth rate led us to suspect a malignancy. A trans-bronchial biopsy was undiagnostic and a video-assisted thoracic surgery was planned. She underwent a wedge resection of the right lung, and a histopathological examination found it was a metastatic leiomyosarcoma.ConclusionsA pulmonary metastasis from a leiomyosarcoma could emerge as an SPN and reveal a subsequent transient size reduction. An SPN in patients even with a remote history of a soft tissue tumor should raise the possibility of metastasis, and periodic follow-up is essential even after the size reduction.

Management of hemoptysis with bronchial artery embolization: Benign versus malignant indications

Objectives: The purpose of this study is to compare the role of bronchial artery embolization (BAE) in hemoptysis due to malignant and non-malignant etiologies. Material and Methods: Data from patients who underwent BAE at a tertiary care center from October 2002 to 2018 were retrospectively reviewed. Variables evaluated include procedural indication, technical success, clinical success, re-embolization, intensive care unit (ICU) admission, length of stay, and thirty-day readmission. Categorical and continuous variables were analyzed using Pearson’s Chi-squared and two sample t-tests, respectively. Post-procedure survival and re-embolization were analyzed using Kaplan–Meier curves and Cox proportional hazard models. Results: 114 BAE procedures from 93 unique patients with hemoptysis were identified, with 29.8% of procedures being performed for hemoptysis secondary to malignancy and 70.2% for benign causes. The technical and clinical success rates of the procedure were similar between benign and malignant etiologies (benign/malignant: 92.5% vs. 91.2% and 82.5% vs. 73.5%, respectively). There were no statistically significant differences in rates of need for re-embolization, ICU admission, 30-day readmission, mean hospital length of stay, or mortality between benign and malignant groups. Clinically successful embolization was protective against death (HR = 0.19, P &lt; 0.001) and re-embolization (HR = 0.04, P = 0.001), while higher American Society of Anesthesiologists’ (ASA) score, female sex, and primary pulmonary malignancy were associated with risk of death. Conclusion: While patients with a malignant cause of hemoptysis had an increased risk of mortality and decreased survival time, BAE for malignant hemoptysis is effective with outcomes comparable to that for benign hemoptysis as indicated by high clinical and technical success rates and low rates of re-embolization.

Advantages of Total Bilirubin for Predicting Malignant Obstructive Jaundice, A Combination of the Pandemic Era and Limited Resources Settings

BACKGROUND: Hepatopancreatobiliary (HPB) cancer incidence and mortality are increasing worldwide. An initial diagnostic predictor is needed for recommending further diagnostic modalities, referral, and curative or palliative decisions. There were no studies conducted in area with limited accessibility setting of the COVID-19 pandemic, coupled with limited human resources and facilities. AIM: We aimed to investigate the advantages of total bilirubin for predicting malignant obstructive jaundice, a combination of the pandemic era and limited resources settings. METHODS: Data from all cholestasis jaundice patients at M. Djamil Hospital in Pandemic COVID-19 period from July 2020 to May 2022 were retrospectively collected. The data included demographics, bilirubin fraction results, and final diagnosis. Bivariate analysis for obtain demographic risk factor, and Receiver Operating Characteristics (ROC) analysis for getting bilirubin value. RESULTS: Of a total 132 patients included, 35.6% were malignant obstructive jaundice, and Pancreatic adeno ca was the most malignant etiology (34.4%). Bivariate analysis showed a significant correlation between age and malignant etiology (p = 0,024). Direct and total Bilirubin reach the same level of Area Under Curve (AUC). Total bilirubin at the cutoff point level of 10.7 mg/dl had the most optimal results on all elements of ROC output, AUC 0.88, sensitivity 76.6%, specificity 90.1%, +LR 8.14, and -LR 0.26. CONCLUSION: The bilirubin fraction is a good initial indicator for differentiating benign and malignant etiology (AUC 0.8–0.9) in pandemic era and resource-limited areas to improve diagnostic effectiveness and reduce referral duration.

Diagnostic Accuracy of Clinical Features, Laboratory Features, and Ultrasound Imaging Compared to Intraoperative Findings in Patients with Obstructive Jaundice

Highlights:1. Patients with obstructive jaundice have either benign or malignant underlying etiologies.2. Ultrasound imaging had the highest accuracy in diagnosing the etiology of obstructive jaundice among other examinations, such as clinical signs and laboratory tests. AbstractIntroduction: Jaundice due to biliary obstruction can be caused by a diverse group of diseases, including both benign and malignant etiologies. This study aimed to evaluate the accuracy of clinical features, laboratory features, and ultrasound imaging in diagnosing the etiology of obstructive jaundice with intraoperative findings as the gold standard.Methods: This was an observational cross-sectional analytic study conducted on 49 subjects by obtaining patients’ data from medical records in the Medical Record Center Dr. Soetomo General Academic Hospital, Surabaya. Collected data were statistically analyzed using a diagnostic test.Results: In this study, sensitivity (Sn), specificity (Sp), and accuracy of each feature in differentiating masses and stones as the etiology of obstructive jaundice were obtained. Progressive jaundice had Sn 88.2%, Sp 37%, and accuracy 56.8%. Complaints of fever had Sn 73.9%, Sp 90.9%, and accuracy 79.4%. Courvoisier’s law had Sn 61.5%, Sp 61.5%, and accuracy 61.5%. Serum CA 19-9 had Sn 75%, Sp 58.3%, and accuracy 67.9%. Ultrasound imaging had Sn 81.8%, Sp 100%, and accuracy 93.3%.Conclusion: Ultrasound imaging had the highest accuracy in diagnosing the etiology of obstructive jaundice, followed by complaints of fever, serum CA 19-9, Courvoisier’s law, and progressive jaundice, respectively.

Case Report: Right atrial organized thrombus three years after tricuspid annuloplasty

Background: Occurrence of right atrial masses, especially in patients with history of cardiac surgery, is rare. Differential diagnosis between malignant and non-malignant aetiologies might be cumbersome, and surgery is often required to prevent complications or disease evolution. Case: We report the case of a 16-year-old girl from a rural area of Sudan, who underwent surgery for a modified De Vega’s tricuspid annuloplasty, and mitral and aortic valve replacement with mechanical prostheses. The patient was on regular follow-up but demonstrated a poor compliance to anticoagulation therapy with a time in therapeutic range between 52% and 20%. She remained asymptomatic, but a right atrial mass was diagnosed by transthoracic echocardiography during a follow-up visit 41 months after the first operation. Surgical removal of the mass revealed an organized thrombus arising from the point where the Prolene stitches for the tricuspid annuloplasty were previously passed. The patient recovered from surgery, was discharged home on post-operative day 10 and the first follow-up visit at 30 days after discharge confirmed a good clinical status and a normal transthoracic echocardiography (TTE). Conclusions: This case report describes the diagnostic and therapeutic work-out of a thrombus formation on the suture lines of a tricuspid annuloplasty. Moreover, it highlights the importance of a strict and long follow-up after valvular surgery and of the adherence to anticoagulation therapy, especially for patients living in rural areas of developing countries.

Cytomorphological analysis of effusion fluids for detection of malignant cells in a tertiary care hospital in northern India.

All body cavities are lined by monolayered mesothelial cells and contain a minimal amount of fluid for lubrication and for protecting the underlying viscera. The peritoneal, pleural, cerebrospinal, sputum, urine, and pericardial fluids comprise the major chunk of body fluids. The study was conducted in the Department of Pathology of a tertiary care hospital in northern India, over a period of 1 year, from January 2021 to December 2021. A total of 241 samples were included in the study. Out of the 241 samples studied, 99 were peritoneal fluid, 94 were pleural fluids, 29 were CSF, and 18 were sputum samples. Maximum number of patients affected were in the age group of 41-50 years. Female preponderance was seen with male to female ratio of 1:1.7. A total of 143/241 cases (59.33%) were of transudative nature and 98/241 (27.8%) cases were exudative. Out of 241 cases, 43 (17.84%) were neoplastic, 190 (78.83%) were non-neoplastic, four (1.65%) were suspicious for malignancy, and four (1.65%) were where no opinion was possible. Peritoneal fluid was the most frequently encountered fluid accounting for 99 cases (41.07%). Adenocarcinoma was the most common malignancy accounting for 29 cases (67.44%) out of 43 malignant effusions in the present study. Cytological evaluation of body fluids is of significant utility in diagnostic medicine as it allows us to distinguish between benign and malignant etiologies and at the same time offers rapid diagnosis and staging of metastatic disease.

Bacteriobilia frequency in patients afflicted by biliary obstruction at a tertiary care center

Background: Bile typically remains sterile within individuals possessing a normal biliary tract, but bacterial colonization arises with biliary obstruction. Infections often stem from ascending duodenal infection or bacterial translocation from the portal vein. Elevated common bile duct pressure due to obstruction, combined with infected bile, can lead to bacterial backflow into lymphatics, fostering cholangitis. In this study, 30 sequential bile samples were examined, scrutinizing the occurrence of bacteriobilia and comparing its incidence between benign and malignant etiologies. Aims and Objectives: Bacteriobilia typically manifests without symptoms. This study aimed to assess the prevalence of bacteriobilia in patients with obstructive jaundice undergoing endoscopic retrograde cholangiopancreatography (ERCP) at our institution, investigating associated risk factors. Furthermore, the study aimed to elucidate the microbiological profile of bile in obstructed biliary systems, make a comparative analysis of bacteriobilia frequency between benign and malignant obstructions, and delve into the drug sensitivity patterns of bacteria cultured from bile at our center. Materials and Methods: In a prospective, observational, and diagnostic study conducted at the Department of Digestive Health and Diseases, Government Peripheral Hospital, Anna Nagar, Chennai, from September 2011 to February 2012, with ethical committee approval and informed consent from all participants, we investigated 30 consecutive patients who underwent ERCP for biliary obstruction. The study cohort comprised 13 males and 17 females. Following successful biliary cannulation, bile samples were collected and subjected to microbiological analysis. Results revealed positive bile cultures in 16 patients, with 10 exhibiting benign etiology and 6 malignant. Gram-negative organisms, predominantly Klebsiella, were identified, displaying favorable susceptibility to cephalosporins while demonstrating resistance to ciprofloxacin. Results: Bile cultures yielded positive results in 16 patients, with 10 cases attributed to benign etiology and 6 to malignant etiology. The cultured organisms were predominantly Gram-negative, with Klebsiella exhibiting significant growth. Notably, these organisms exhibited favorable susceptibility to cephalosporins while displaying resistance to ciprofloxacin. Conclusion: Bile culture serves as a valuable tool for prompt diagnosis and pre-emptive management of complications. Gram-negative bacilli infections prevail within obstructed biliary systems. This study underscores the pivotal role of routine bile sampling during ERCP in obstructed biliary systems, offering predictive insights to avert complications like cholangitis.

Etiopatogenia da fratura patológica mandibular: revisão de literatura e relatos de caso

ABSTRACT Pathological mandibular fractures are fractures induced by pathologies affecting the mandible’s base or those resulting from forces that would typically be tolerable if the bone were not compromised by an underlying condition. These fractures often present complex clinical scenarios owing to the compromised bone integrity caused by the pathology, which impedes resolution. Systemic changes may also diminish the capacity for bone neoformation, significantly limiting therapeutic options. Therefore, this study aimed to provide a comprehensive review of the published scientific literature and present clinical cases related to the treatment and prevention of pathological mandibular fractures. A literature review was conducted, focusing on case reports indexed in the MEDLINE and SCIELO databases using specific keywords as descriptors. The search yielded ten articles, which described the etiopathogenesis, classified as infectious, idiopathic, benign pathology, malignant pathology, and iatrogenic. The literature suggests that prioritizing surgery to address the underlying local pathology is crucial. Managing the remaining bone defect optimally may necessitate multiple surgical interventions. Furthermore, preventive measures should be implemented in potential iatrogenic cases. Notably, fractures of malignant, idiopathic, hereditary, and metabolic etiologies may indicate the initial manifestation of diseases.

Lockdown period during SARS COVID-19 endemic outbreak in Taiwan did not cause an increase of the complications nor mortality of patients received endoscopic retrograde cholangiopancreatography: A single-center retrospective study.

Coronavirus disease 2019, known as a widespread, aerosol spreading disease, has affected >549 000 000 people since 2019. During the lockdown period, dramatic reduction of elective endoscopic procedures, including endoscopic retrograde cholangiopancreatography, had been reported worldwide, leading to delayed diagnosis and treatment. Nevertheless, whether patients' hospital stays and complication rate of endoscopic retrograde cholangiopancreatography (ERCP) during the lockdown period were influenced by the pandemic still remains controversial. Patients who diagnosed with obstructive jaundice and acute cholangitis in the lockdown period, May 16 to July 26, 2021, were compared to the same prepandemic period in 2019. A total of 204 patients in 2019 and 168 patients in 2021 were diagnosed with acute biliary cholangitis or obstructive jaundice, and 82 of the patients in 2019 and 77 patients in 2021 underwent ERCP ( p = 0.274). Patients whose quick Sequential Organ Failure Assessment (qSOFA) score was ≥ 2 occurred more during the lockdown period than during the normal period (24/77, 31.1% vs 12/82, 14.6%; p = 0.013). The initial laboratory data, including, total bilirubin (4.12 in 2021 vs 3.08 mg/dL in 2019; p = 0.014), gamma-glutamyl transferase (378 in 2021 vs 261 U/L in 2019; p = 0.009), and alkaline phosphatase (254 in 2021 vs 174 U/L in 2019; p = 0.002) were higher during the lockdown period compared to 2019. Hospital stay was statistically significant longer in the lockdown period (11 days [7.00-22.00] in 2021 vs 8 days in 2019 [6.00-12.00]; p value = 0.02). Multivariate analysis showed that qSOFA ≥ 2 (hazard ratio [HR] = 3.837, 95% confidence interval [CI] = 1.471-10.003; p = 0.006), and malignant etiology (HR = 2.932, 95% CI = 1.271-6.765; p = 0.012) were the statistically significant factors for a prolonged hospital stay, which was defined as hospital stay >21 days. ERCP-related complications and mortality rate were not statistically different between the two periods. Patients from May 16 to July 26, 2021, the lockdown period, had longer hospital stays and higher biliary tract enzyme levels, which indicated more severe disease. Nevertheless, ERCP could be safely and successfully performed even during the medical level 3 alert lockdown period without causing an increase in procedure-related complications and mortality.

Sinonasal Synovial Sarcoma Masquerading as A Common Soft Tissue Tumor: A Diagnostic Challenge and Literature Review

Synovial sarcoma is a malignant soft tissue neoplasm which amounts to 7-10% of all sarcomas. Clinicopathological heterogeneity within this tumour creates a diagnostic challenge in sorting it out from its differential diagnoses. Here we report a 42-year-old female patient presenting with a mass in the right nasal cavity for two months. With an imaging impression of a right ethmoidal polyp with a remote possibility of malignant etiology, a final diagnosis of sinonasal synovial sarcoma was made with the help of a panel of IHC antibodies. A high degree of suspicion along with a detailed work up is required to accurately diagnose synovial sarcoma in unlikely locations such as nasal cavity. Keywords: Synovial sarcoma, Nasal cavity, TLE­1, BCL2, SOX 10

A virtual screening investigation to identify bioactive natural compounds as potential inhibitors of cyclin-dependent kinase 9

Cyclin-dependent kinase 9 (CDK9) is a transcription-associated protein involved in controlling the cell cycle and is often deregulated in stress conditions. CDK9 is being studied as a well-known druggable target for developing effective therapeutics against a wide range of cancer, cardiac dysfunction and inflammatory diseases. Owing to the significance of CDK9 in the etiology of hematological and solid malignancies, its structure, biological activity, regulation and its pharmacological inhibition are being explored for therapeutic management of cancer. We employed a structure-based virtual high-throughput screening of bioactive compounds from the IMPPAT database to discover potential bioactive inhibitors of CDK9. The preliminary results were obtained from the Lipinski criteria, ADMET parameters and sorting compounds without any PAINS patterns. Subsequently, binding affinity and selectivity analyses were used to find effective CDK9 hits. This screening resulted in the identification of two natural compounds, Glabrene and Guggulsterone with high affinity and specificity for the CDK9 binding site. Both compounds exhibit drug-like characteristics, as projected by ADMET analysis, physicochemical data and PASS evaluation. Both compounds preferentially bind to the ATP-binding pocket of CDK9 and interact with functionally important residues. Further, the dynamics and consistency of CDK9 interaction with Glabrene and Guggulsteron were evaluated through all-atom molecular dynamic (MD) simulations which suggested the stability of both complexes. The results might be deployed to introduce novel CDK9 inhibitors that may treat life-threatening diseases, including cancer. Communicated by Ramaswamy H. Sarma

Assessment of diaphragmatic role in dyspneic patients with pleural effusion

BackgroundDyspnea that is caused by pleural effusion and affects patients’ quality of life may not be resolved after lung expansion following pleural tapping. This study aims to investigate the role that changes in the diaphragmatic shape and movement play in the development of dyspnea in those patients.MethodsThirty patients with pleural effusions and dyspnea were evaluated before and at 24 h after therapeutic thoracentesis. The primary outcomes are to investigate changes in diaphragmatic shape and movement before and after thoracentesis by chest ultrasound to evaluate factors causing effusion-related dyspnoea, while the secondary outcomes are firstly to investigate the effect of pleural effusion on the cardiorespiratory, functional, and diaphragmatic variables in causing dyspnea and secondly to detect the percentages and demographics of patients who experience post-drainage dyspnea improvement.ResultsThirty patients with age >18 years old who had moderate to massive pleural effusion (either of benign or malignant etiology), with breathlessness were recruited from the Chest Department, Ultrasonography Unit, Ain-Shams University Hospitals. Almost all (96.7%) of the studied patients experienced shortness of breath with a mean modified Borg Score of 5.13 ± 1.78, tapping of varying amounts of pleural fluid ranging from 1000 to 2000 ml.There is a highly significant improvement in the diaphragmatic excursion, with non-significant improvement in diaphragmatic shape, although nonsignificant correlation between diaphragmatic excursion and functional parameters (M. Borg score, spirometry, and 6MWD: 6-min walk distance), but a significant negative correlation between diaphragmatic excursion and amount of drained effusion (P value 0.045 and 95% CI for OR 1.041–36.779). 63.3% of patients experienced dyspnea improvement after thoracocentesis, and they showed highly significant improvements in M. Borg dyspnea score, spirometry, pulse rate, respiratory rate, 6MWD, and blood oxygen saturation.ConclusionIn this study, we conclude that the improvement of the diaphragmatic excursion was negatively correlated with the amount of drained effusion, but no significant correlation was detected with the functional parameters and effusion-related indices that may be caused by the small sample size of the study.

Biliary system interventions : Percutaneous transhepatic cholangiodrainage to bilioma

Avariety of transhepatic percutaneous biliary procedures are appropriate for the treatment of pathologies of the biliary system. The aim of this article is to describe best practices for performing percutaneous transhepatic cholangiography with placement of abiliary drain (PTCD), percutaneous transhepatic removal of bile duct stones, percutaneous stenting of the bile ducts, and percutaneous treatment of postoperative bilioma. The authors reviewed existing literature on relevant current recommendations and presented them based on their own facility's approach. Biliary interventions are mostly aimed at treating some form of cholestasis of benign or malignant etiology. The technical success rate is up to 90%. Percutaneous biliary interventions are safe and effective procedures in the treatment of pathologies of the biliary system, preferably used when endoscopic access is not possible due to anatomical conditions.

Cancer Patients and the COVID-19 Vaccines: Considerations and Challenges.

Few guidelines exist for COVID-19 vaccination amongst cancer patients, fostering uncertainty regarding the immunogenicity, safety, and effects of cancer therapies on vaccination, which this review aims to address. A literature review was conducted to include the latest articles covering the immunogenicity and safety of COVID-19 vaccination in patients with solid and hematologic cancers receiving various treatments. Lower seropositivity following vaccination was associated with malignancy (compared to the general population), and hematologic malignancy (compared to solid cancers). Patients receiving active cancer therapy (unspecified), chemotherapy, radiotherapy, and immunosuppressants generally demonstrated lower seropositivity compared to healthy controls; though checkpoint inhibition, endocrine therapy, and cyclin dependent kinase inhibition did not appear to affect seropositivity. Vaccination appeared safe and well-tolerated in patients with current or past cancer and those undergoing treatment. Adverse events were comparable to the general population, but inflammatory lymphadenopathy following vaccination was commonly reported and may be mistaken for malignant etiology. Additionally, radiation recall phenomenon was sporadically reported in patients who had received radiotherapy. Overall, while seropositivity rates were decreased, cancer patients showed capacity to generate safe and effective immune responses to COVID-19 vaccination, thus vaccination should be encouraged and hesitancy should be addressed in this population.

The Role of Adult Cancer Predisposition Genes in Hematological Malignancies of Childhood

Background: Increasing evidence suggests that adult cancer genes (ACGs) contribute substantially to the development of several malignancies in childhood, although with reduced penetrance. The association of BRCA1 and BRCA2 with breast and ovarian cancer is sufficiently described, as well as the presence of heterozygous mutations in one of the mismatch repair genes (MSH2, MSH6, MLH1, PMS2) in hereditary colon carcinoma. Moreover, there is a plethora of genes, mainly regulating DNA repair mechanisms and cell cycle arrest as BRIP1, CHEK2, ATM, PALB2, HOXB13, RAD51C, RAD51D, which predispose to a variety of adult type cancers. The recurrent presence of pathogenic variants in one of the ACGs is observed in several pediatric cancer cohorts and gaining recognition in the field of pediatric cancer susceptibility. However, the incidence and impact of ACGs in childhood cancer and especially in pediatric hematological malignancies is not fully explored yet. Aims: Our aim is to understand the frequency and the impact of germline variants in adult cancer predisposition genes in the etiology of hematological malignancies in children. Methods: We analyzed parent-child whole exome sequencing (WES) data of 162 children (<18yrs) with hematological malignancies (N=117 leukemia, N=43 lymphoma, N=2 myelodysplastic syndrome) for the presence of pathogenic variants in adult onset cancer predisposition genes. For part of the detected variants, we performed further functional analysis to investigate the effect of the alteration on protein function. Results: We diagnosed a classical cancer predisposition syndrome associated with the respective hematological malignancy in 5/162 patients (3%): Li-Fraumeni (N=1), Constitutional mismatch repair deficiency (CMMRD) (N=1), Nijmegen-Breakage syndrome (NBS) (N=1) and Noonan syndrome (N=2). Additionally we identified in 19/162 patients a pathogenic / likely pathogenic variant (P/LP) in one of the ACGs, including BRIP1, CHEK2, HOXB13, BRCA1, MSH2 and STK11. Strikingly, we observed a high frequency of CHEK2 germline variants in our cohort (15/162) (Figure 1A). The majority of those patients had a leukemia (N=11 BCP-ALL, N=1 T-ALL, N=1 CML) and two patients were diagnosed with a Hodgkin lymphoma. Interestingly, eight different CHEK2 variants including three truncating variants were detected in our cohort. Three variants were recurrent (p.Ile157Thr N=5, p.Ile160Met N=3, p.Thr367Metfs*15 N=2). According to the classification of the American College of Medical Genetics and Genomics 7/8 variants identified in 14 patients were predicted to be pathogenic or likely pathogenic. For two of these variants an impaired function had been already described in the literature. To test the functional consequences of the five remaining variants, we overexpressed these, in comparison to two control CHEK2 variants, in U2OS cells. Four out of seven variants (N=1 truncating, N=1 in-frame deletion, N=2 missense) led to loss of protein expression (Figure 1B) and loss of CHEK2-Thr68 phosphorylation upon irradiation induced DNA damage. Hence, according to the functional analysis, five out of fifteen patients carried a CHEK2 variant impairing its function. Interestingly, 4/5 patients with a pathogenic variant had a BCP-ALL and 1/5 had a BCR-ABL CML that rapidly progressed to lymphoid blast crisis while under imatinib therapy (400 mg/m2). Conclusion/Summary: We identified heterozygous pathogenic variants in ACGs in the germline of 11.7% of children with hematological malignancies by WES-based screening of 162 cases. Strikingly 14/162 patients (8,6%) harbored a P/LP variant in the CHEK2 gene. Functional studies revealed that five patients carried a germline variant leading to loss of CHEK2 expression and/or loss of Thr68 phosphorylation upon irradiation. We conclude that impaired CHEK2 function may be an important germline-encoded host factor predisposing to the development of hematological malignancies in children. Figure 1 (A): Schematic representation of the CHEK2 protein indicating the localization of the identified variants. The length of the bars correlates to the number of patients with the respective CHEK2 variant and the color of the bars to the variant type (green: missense, red: frameshift indels, orange: splicing). (B): Western blot analysis of HA-tagged CHEK2 protein variants ectopically expressed in U2OS cells. GAPDH was used as a loading control. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abnormal TSH Prior to Surgery in Children with Graves' Disease Predicts Abnormal TSH Following Thyroidectomy.

To identify variables that are associated with poor compliance to thyroid hormone replacement therapy in children after total thyroidectomy. A retrospective cohort study of children who underwent total thyroidectomy by high-volume pediatric otolaryngologists between 1/2014 and 9/2021. Postoperative poor compliance was characterized by at least three separate measurements of high TSH levels not associated with radioactive iodine treatment. There were 100 patients, ages 3-20 years old who met inclusion criteria; 44 patients underwent thyroidectomy for cancer diagnosis, and 56 for Graves' disease. The mean follow-up time was 36.5 months (range 3.0-95.6 months). Overall, 42 patients (42%) were found to have at least three measurements of high TSH during follow-up, and 29 patients (29%) were diagnosed with clinical hypothyroidism. Sex, race, income, insurance type, and benign versus malignant etiology for thyroidectomy were not associated with adherence to therapy. Multivariate regression analysis identified patients with Graves' disease and hyperthyroidism at the time of surgery and Hispanic ethnicity to be associated with postoperative clinical hypothyroidism (OR 9.38, 95% CI 2.16-49.2, p=0.004 and OR 6.15, 95% CI 1.21-36.0, p=0.033, respectively). Preoperative hyperthyroidism in patients with Graves' disease and Hispanic ethnicity were predictors of postoperative TSH abnormalities. Preoperative counseling for patients and their families on the implications of total thyroidectomy and the need for life-long medications postoperatively is necessary. Efforts should be made to evaluate and improve adherence to therapy pre-and postoperatively in patients with Graves' disease. 4 Laryngoscope, 133:2402-2406, 2023.