A new label free spiral sensor using impedance spectroscopy to characterize hepatocellular carcinoma in tissue and serum samples.

Hepatocellular carcinoma (HCC) stands as the most prevalent form of primary liver cancer, predominantly affecting patients with chronic liver diseases such as hepatitis B or C-induced cirrhosis. Diagnosis typically involves blood tests (assessing liver functions and HCC biomarkers), imaging procedures such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), and liver biopsies requiring the removal of liver tissue for laboratory analysis. However, these diagnostic methods either entail lengthy lab processes, require expensive imaging equipment, or involve invasive techniques like liver biopsies. Hence, there exists a crucial need for rapid, cost-effective, and noninvasive techniques to characterize HCC, whether in serum or tissue samples. In this study, we developed a spiral sensor implemented on a printed circuit board (PCB) technology that utilizes impedance spectroscopy and applied it to 24 tissues and sera samples as proof of concept. This newly devised circuit has successfully characterized HCC and normal tissue and serum samples. Utilizing the distinct dielectric properties between HCC cells and serum samples versus the normal samples across a specific frequency range, the differentiation between normal and HCC samples is achieved. Moreover, the sensor effectively characterizes two HCC grades and distinguishes cirrhotic/non-cirrhotic samples from tissue specimens. In addition, the sensor distinguishes cirrhotic/non-cirrhotic samples from serum specimens. This pioneering study introduces Electrical Impedance Spectroscopy (EIS) spiral sensor for diagnosing HCC and liver cirrhosis in clinical serum-an innovative, low-cost, rapid (< 2 min), and precise PCB-based technology without elaborate sample preparation, offering a novel non-labeled screening approach for disease staging and liver conditions.

Evaluation of Patient Education Materials From Large-Language Artificial Intelligence Models on Carpal Tunnel Release.

BACKGROUND: ChatGPT, an artificial intelligence technology, has the potential to be a useful patient aid, though the accuracy and appropriateness of its responses and recommendations on common hand surgical pathologies and procedures must be understood. Comparing the sources referenced and characteristics of responses from ChatGPT and an established search engine (Google) on carpal tunnel surgery will allow for an understanding of the utility of ChatGPT for patient education. METHODS: A Google search of "carpal tunnel release surgery" was performed and "frequently asked questions (FAQs)" were recorded with their answer and source. ChatGPT was then asked to provide answers to the Google FAQs. The FAQs were compared, and answer content was compared using word count, readability analyses, and content source. RESULTS: There was 40% concordance among questions asked by the programs. Google answered each question with one source per answer, whereas ChatGPT's answers were created from two sources per answer. ChatGPT's answers were significantly longer than Google's and multiple readability analysis algorithms found ChatGPT responses to be statistically significantly more difficult to read and at a higher grade level than Google's. ChatGPT always recommended "contacting your surgeon." CONCLUSION: A comparison of ChatGPT's responses to Google's FAQ responses revealed that ChatGPT's answers were more in-depth, from multiple sources, and from a higher proportion of academic Web sites. However, ChatGPT answers were found to be more difficult to understand. Further study is needed to understand if the differences in the responses between programs correlate to a difference in patient comprehension.

Activation of p53 signaling and regression of breast and prostate carcinoma cells by spirooxindole-benzimidazole small molecules.

This study discusses the synthesis and use of a new library of spirooxindole-benzimidazole compounds as inhibitors of the signal transducer and activator of p53, a protein involved in regulating cell growth and cancer prevention. The text includes the scientific details of the [3 + 2] cycloaddition (32CA) reaction between azomethine ylide 7a and ethylene 3a within the framework of Molecular Electron Density Theory. The mechanism of the 32CA reaction proceeds through a two-stage one-step process, with emphasis on the highly asynchronous transition state structure. The anti-cancer properties of the synthesized compounds, particularly 6a and 6d, were evaluated. The inhibitory effects of these compounds on the growth of tumor cells (MDA-MB 231 and PC-3) were quantified using IC50 values. This study highlights activation of the p53 pathway by compounds 6a and 6d, leading to upregulation of p53 expression and downregulation of cyclin D and NF-κB in treated cells. Additionally, we explored the binding affinity of spirooxindole analogs, particularly compound 6d, to MDM2, a protein involved in regulation of p53. The binding mode and position of compound 6d were compared with those of a co-crystallized standard ligand, suggesting its potential as a lead compound for further preclinical research.

Exploring pyrrolidinyl-spirooxindole natural products as promising platforms for the synthesis of novel spirooxindoles as EGFR/CDK2 inhibitors for halting breast cancer cells.

Cancer represents a global challenge, and the pursuit of developing new cancer treatments that are potent, safe, less prone to drug resistance, and associated with fewer side effects poses a significant challenge in cancer research and drug discovery. Drawing inspiration from pyrrolidinyl-spirooxindole natural products, a novel series of spirooxindoles has been synthesized through a one-pot three-component reaction, involving a [3 + 2] cycloaddition reaction. The cytotoxicity against breast cancer cells (MCF-7 and MDA-MB-231) and safety profile against WISH cells of the newly developed library were assessed using the MTT assay. Compounds 5l and 5o exhibited notable cytotoxicity against MCF-7 cells (IC50 = 3.4 and 4.12 µM, respectively) and MDA-MB-231 cells (IC50 = 8.45 and 4.32 µM, respectively) compared to Erlotinib. Conversely, compounds 5a-f displayed promising cytotoxicity against MCF-7 cells with IC50 values range (IC50 = 5.87-18.5 µM) with selective activity against MDA-MB-231 cancer cells. Compound 5g demonstrated the highest cytotoxicity (IC50 = 2.8 µM) among the tested compounds. Additionally, compounds 5g, 5l, and 5n were found to be safe (non-cytotoxic) against WISH cells with higher IC50 values ranging from 39.33 to 47.2 µM. Compounds 5g, 5l, and 5n underwent testing for their inhibitory effects against EGFR and CDK-2. Remarkably, they demonstrated potent EGFR inhibition, with IC50 values of 0.026, 0.067, and 0.04 µM and inhibition percentages of 92.6%, 89.8%, and 91.2%, respectively, when compared to Erlotinib (IC50 = 0.03 µM, 95.4%). Furthermore, these compounds exhibited potent CDK-2 inhibition, with IC50 values of 0.301, 0.345, and 0.557 µM and inhibition percentages of 91.9%, 89.4%, and 88.7%, respectively, in contrast to Roscovitine (IC50 = 0.556 µM, 92.1%). RT-PCR analysis was performed on both untreated and 5g-treated MCF-7 cells to confirm apoptotic cell death. Treatment with 5g increased the gene expression of pro-apoptotic genes P53, Bax, caspases 3, 8, and 9 with notable fold changes while decreasing the expression of the anti-apoptotic gene Bcl-2. Molecular docking and dynamic simulations (100 ns simulation using AMBER22) were conducted to investigate the binding mode of the most potent candidates, namely, 5g, 5l, and 5n, within the active sites of EGFR and CDK-2.

Adverse Events of the Long-Term Use of Opioids for Chronic Non-cancer Pain: A Narrative Review.

BACKGROUND: The long-term use of opioids for chronic non-cancer pain (CNCP) has drawn more attention and debate. Although opioids are frequently used to treat chronic pain, their effectiveness and safety over extended periods are still unknown. OBJECTIVES: The purpose of this review is to provide an overview of what is currently known about the adverse events of long-term use of opioids in CNCP. It also delivers patient-centered strategies designed to mitigate these risks. METHODS: We conducted a literature search in PubMed, MEDLINE, EMBASE, and Web of Science databases. Search terms included CNCP, pain pathophysiology, opioid pharmacodynamics, opioid prescribing trends, guidelines for opioid use, and opioid side effects.  Results: Our review highlights that while opioids may provide short-term relief from CNCP, their effectiveness diminishes over time due to the development of opioid tolerance. This tolerance often leads to increased dosages, which can subsequently result in opioid dependence. Additionally, long-term opioid therapy is associated with a spectrum of adverse effects, including constipation, drowsiness, respiratory depression, and potential for drug interactions. Furthermore, our review indicates that alternative pain management strategies play a crucial role in controlling CNCP. They offer significant benefits with fewer adverse events. These strategies include non-opioid medications, physical therapy, cognitive-behavioral therapy (CBT), various interventional procedures, injection therapy, and acupuncture. CONCLUSION: Using opioids to manage CNCP presents several challenges. Given these challenges, alternative treatments are being considered as viable options. Moreover, it is crucial to customize treatment plans to align with the patients' specific health requirements, existing conditions, and potential risks to ensure the best possible outcomes.

Microsurgical Digits Replantation in Resource-Limited Setting: A Retrospective Study.

Background: This article aims to share our experiences with microsurgical finger replantation in a resource-limited setting. Methods: This multi-institutional, retrospective study included 21 cases of finger amputation that underwent microsurgical replantation, within 7 years period. Patient demographics, preoperative assessments, surgical approaches, and outcomes were documented and analyzed. A univariate analysis was performed to obtain factors associated with digit reimplantation failure. Results: Out of 21 cases included, 8 (38.1%) had complete amputations and 13 (61.9%) had incomplete amputations. Crush injuries accounted for the majority (71.4%). On average, 2.2 ± 1.1 digits were affected, with the ring finger being the most commonly injured (71.4%). The mean operative time was 121.5 ± 26.8 minutes. The success rate of digit replantation was 76.2%. During a mean follow-up of 14.3 ± 3.7 months, 85.7% of successfully replanted digits considered their replantation results satisfactory. The majority of replanted digits demonstrated active and effective holding and grasping abilities without pain or instability (76.2%). Replantation failure was associated with a higher number of affected digits (p < 0.001), longer operative time (p = 0.004), complete avulsion (p = 0.003), current smoking (p = 0.025), diabetes (p = 0.006), hypertension (p = 0.047), procedure difficulty score (p= 0.004), and occurrence of complications (p < 0.001). Conclusion: Microsurgical finger replantation can yield favorable outcomes and acceptable survival rates, even within resource-limited settings. However, this procedure requires specialized equipment and personnel that may not be available at all institutions. Influential factors in digit replantation failure, include an increased number of damaged digits, extended operative duration, complete avulsion, current smoking, diabetes, hypertension, procedure difficulty score, and postoperative complications occurrence.

Mechanical thrombectomy for AIS from large vessel occlusion - current trends and future perspectives.

Stroke is found to be one of the global top causes of mortality and the major factor in years of life with a handicap (DALYs). Ischemic strokes contributed to nearly 70% of all strokes worldwide. For endovascular thrombectomy in acute ischemic stroke with large vessel obstruction (AIS-LVO), using stent retrievers and/or reperfusion catheters has become the gold standard of therapy. The methodology involved keyword-based search in databases like PubMed, Embase, and Google Scholar for recent publications on mechanical thrombectomy (MT), AIS, large vessel occlusion (Large Vessel Occlusion (LVO)), screening relevant articles, retrieving full texts, and synthesizing key findings on procedural advancements, patient selection, COVID-19 (coronavirus disease 2019) impact, delay effects, effectiveness, clinical outcomes, and future perspectives. Only people with substantial cerebral artery obstruction may do well from MT. This includes the distal carotid artery and the proximal middle cerebral artery (segment M1). The size of a blocked vessel and NIHSS (National Institute of Health Stroke Scale) score are directly connected. Both the 2018 and 2019 versions of the AHA/ASA (American Heart Association/American Stroke Association) Guidelines for the Early Management of Patients with Acute Ischemic Stroke contained the recommendations that cases with AIS-LVO get endovascular therapy when administered during the time frame of 0-6 h after onset (Grade IA evidence). It is questionable whether this group of patients can be managed without the need for intravenous tissue plasminogen activator at the onset. When functional independence [modified Rankin Scale (mRS) score 2] was present at long-term follow-up, the endovascular intervention was favored. Tenecteplase, which differs from alteplase in terms of genetic variation, has a greater half-life and a higher level of fibrin selectivity, enabling bolus infusion. Studies have also demonstrated its efficacy and safety, as well as its long-term cost-effectiveness.

New spiro-indeno[1,2-b]quinoxalines clubbed with benzimidazole scaffold as CDK2 inhibitors for halting non-small cell lung cancer; stereoselective synthesis, molecular dynamics and structural insights.

Despite the crucial role of CDK2 in tumorigenesis, few inhibitors reached clinical trials for managing lung cancer, the leading cause of cancer death. Herein, we report combinatorial stereoselective synthesis of rationally designed spiroindeno[1,2-b]quinoxaline-based CDK2 inhibitors for NSCLC therapy. The design relied on merging pharmacophoric motifs and biomimetic scaffold hopping into this privileged skeleton via cost-effective one-pot multicomponent [3 + 2] cycloaddition reaction. Absolute configuration was assigned by single crystal x-ray diffraction analysis and reaction mechanism was studied by Molecular Electron Density Theory. Initial MTT screening of the series against A549 cells and normal lung fibroblasts Wi-38 elected 6b as the study hit regarding potency (IC50 = 54 nM) and safety (SI = 6.64). In vitro CDK2 inhibition assay revealed that 6b (IC50 = 177 nM) was comparable to roscovitine (IC50 = 141 nM). Docking and molecular dynamic simulations suggested that 6b was stabilised into CDK2 cavity by hydrophobic interactions with key aminoacids.

The Epidemiological Pattern of Skin Cancer from 2011 to 2022 among the Population of the Aseer Region, Kingdom of Saudi Arabia.

The overall risk of developing cancer before the age of 75 years in the Kingdom of Saudi Arabia is 9.9%. We aimed to explore the pattern of skin cancer, specifically among the Saudi population residing in the Aseer region. We obtained data from the medical records of Aseer Central Hospital regional histopathological laboratory considering surgical pathology reports from 2011 to 2021. The 61-80-year-old age group represented most of the cases (41.4%), followed by the 41-60-year-old group at 24.1%. Men made up the majority of the cases (59.4%). Furthermore, the dataset predominantly consisted of Saudi nationals (94.3% of the sample). The percentage of cases diagnosed each year relative to the cumulative number of skin cancer cases varied each year, ranging from 1.6% in 2011 to 11.6% in 2017. The most common diagnoses were squamous cell carcinoma (SCC) with 230 cases (41.1%) and basal cell carcinoma (BCC) with 147 cases (26.3%). The majority of cases occurred in the head and neck region (55.4%), followed by the lower limb (16.6%), trunk (13.6%), upper limb (8.2%), and pelvis (2.3%). There was a significant variation in the type of skin cancer across the age groups (p < 0.001) and across different body parts (p < 0.001). The incidence of skin cancer exhibited variability throughout the study period. The predominant diagnoses observed were SSC and BCC. Among the affected areas, the head and neck region displayed the highest prevalence, followed by the lower limb, trunk, upper limb, and pelvis.

Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.

Prevalence and Risk Factors of Renal Stones Among the Bisha Population, Saudi Arabia.

BACKGROUND: In urolithiasis, urinary calculi are formed in the urinary system. Stone development does not initially result in any symptoms, but later renal colic, flank pain, hematuria, obstruction of urine flow, and/or hydronephrosis may indicate renal stone disease. In addition to age, gender, ethnicity, and local climate, urolithiasis can be caused by several other factors. The prevalence and recurrence rate of kidney stone disease is rising globally, while few effective treatment options currently exist. METHODS: Between June and October 2022, a cross-sectional study was conducted. An electronic questionnaire subdivided into three categories was used to determine the prevalence and identify the factors that increase the likelihood of developing urolithiasis among the population in Bisha. The collected data were reviewed and analyzed via IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp. RESULTS: A total of 1,002 participants filled out the questionnaire. The age of the participants ranged from 18 to over 60 years, with an average age of 26.1 ± 13.9 years. There were 451 female participants (45%), and 927 (92.5%) were Saudis. According to the participants' body mass index, 98 (9.8%) were underweight, 388 (38.7%) were normal weight, 300 (29.9%) were overweight, and 216 (21.6%) were obese. The total number of participants with urolithiasis was 161 (16.1%), and 420 (41.9%) had a family history of renal stones. Urolithiasis was found to be significantly associated with family history, smoking, diabetes, hypertension, hyperthyroidism, gout, and chronic kidney disease. Older age and female gender were also associated with the risk of having urolithiasis. CONCLUSION: This study found urolithiasis to be highly prevalent among the Bisha population. In terms of risk factors, body mass index, smoking, and diabetes were the most significant. Based on the findings of this study, the authors recommend more public education regarding urolithiasis and its risk factors, emphasizing the importance of preventing the disease and the ways of treating urolithiasis through medical campaigns and social media.

Malignant testicular tumors in children: overview on 10 years of Saudi Cancer Registry.

BACKGROUND/OBJECTIVE: The aim of this study was to identify epidemiological and histopathological patterns of pediatric testicular tumor (TT) in Saudi population over 10 years. METHODS: Retrospective data extracted from the Saudi Cancer Registry for Saudi children diagnosed with TT from 2008 to 2017. The data collected included patient's factors as age, year of diagnosis, survival status, and tumor factors as basis of diagnosis, origin of the tumor, histopathological group and subtype, and tumor behavior, stage, and laterality. RESULTS: A total of 115 patients with a median age of 14 (IQR 1.5-17) were included. The primary tumor site was a normal descended testis in 98.3% (115). Yolk sac tumor was the most common 28.2% (33), followed by embryonal carcinoma in 27.4% (32) and mixed germ-cell tumors in 23.1% (27). Kaplan-Meier analysis revealed significant association between survival and the stage of the tumor (p = 0.002). However, there was a lack of significant association between survival and age groups, histopathological groups, and histopathological subtypes (p = 0.541, p = 0.609, and p = 0.733, respectively). The overall mortality rate of TT 5.2% with all deaths caused by non-seminomatous germ-cell tumor diagnosed with stage 3. CONCLUSIONS: The median age of the patients was 14 years. Yolk sac tumors were the most common while testicular choriocarcinomas were the least in incidence. No increase in the incidence of TT was seen and the mortality rate over the 10-year period was 5.2%. Shorter survival was associated with higher tumor stage.

Successful Conservative Management of Spontaneous Greater Omental Artery Aneurysm: A Case Report.

Omental hemorrhage is the result of a rupture of the omental vessels. Many causes have been identified to cause omental hemorrhage, which includes trauma, aneurysms, vasculitis, and neoplasms. Spontaneous omental hemorrhage is rare, and usually, patients present with a vague clinical manifestation. In this article, we present the case of a 62-year-old male patient who presented to the emergency department complaining of severe epigastric pain. He was diagnosed by enhanced computed tomography as having a great omental aneurysm and admitted to the surgical ward. The patient was treated conservatively with no apparent complications. Physicians should be made aware of the possibility of great omental bleeding even if none of the mentioned risk factors have been recognized to prevent the life-threatening complications that would follow this condition.

Synthesis and SARs study of novel spiro-oxindoles as potent antiproliferative agents with CDK-2 inhibitory activities.

A series of 16 novel spirooxindole analogs 8a-p were designed and constructed via cost-effective single-step multicomponent [3+2] cycloaddition reaction of azomethine ylide (AY) generated in situ from substituted isatin (6a-d) with suitable amino acids (7a-c) and ethylene-engrafted pyrazole derivatives (5a,b). The potency of all compounds was assayed against a human breast cancer cell line (MCF-7) and a human liver cell line (HepG2). Spiro compound 8c was the most active member among the synthesized candidates, with exceptional cytotoxicity against the MCF-7 and HepG2 cell lines, with IC50 values of 0.189 ± 0.01 and 1.04 ± 0.21 µM, respectively. The candidate 8c exhibited more potent activity (10.10- and 2.27-fold) than the standard drug roscovitine (IC50 = 1.91 ± 0.17 µM (MCF-7) and 2.36 ± 0.21 µM (HepG2)). Compound 8c was investigated for epidermal growth factor receptor (EGFR) inhibition; it exhibited promising IC50 values of 96.6 nM compared with 67.3 nM for erlotinib. The IC50 value of 8c (34.98 nM) exhibited cyclin-dependent kinase 2 (CDK-2) inhibition, being more active than roscovitine the (IC50 = 140 nM) in targeting the CDK-2 kinase enzyme. Additionally, for apoptosis induction of compound 8c in MCF-7, it upregulated the expression levels of proapoptotic genes for P53, Bax, caspases-3, 8, and 9 at up to 6.18, 4.8, 9.8, 4.6, 11.3 fold-change, respectively, and downregualted the level of the antiapoptotic gene for Bcl-2 by 0.14-fold. Finally, a molecular docking study of the most active compound 8c highlighted a good binding affinity with Lys89 as the key amino acid for CDK-2 inhibition.

Presentations and outcomes of familial hemophagocytic lymphohistiocytosis in the pediatric intensive care units (PICUs).

Objectives: We aimed to describe Familial Hemophagocytic Lymphohistiocytosis (F-HLH) patients' clinical features, intensive care courses, and outcomes. Methods: Multi-center retrospective cohort study of pediatric patients diagnosed with F-HLH from 2015 to 2020 in five tertiary centers in Saudi Arabia. Patients were classified as F-HLH based on their genetic confirmation of known mutation or on their clinical criteria, which include a constellation of abnormalities, early disease onset, recurrent HLH in the absence of other causes, or a family history of HLH. Results: Fifty-eight patients (28 male, 30 female), with a mean age of 21.0 ± 33.9 months, were included. The most common principal diagnosis was hematological or immune dysfunction (39.7%), followed by cardiovascular dysfunction in 13 (22.4%) patients. Fever was the most common clinical presentation in 27.6%, followed by convulsions (13.8%) and bleeding (13.8%). There were 20 patients (34.5%) who had splenomegaly, and more than 70% of patients had hyperferritinemia >500 mg/dl, hypertriglyceridemia >150 mg/dl and hemophagocytosis in bone marrow biopsy. Compared to deceased patients 18 (31%), survivors had significantly lower PT (p = 041), bilirubin level of <34.2 mmol/L (p = 0.042), higher serum triglyceride level (p = 0.036), and lesser bleeding within the initial 6 h of admission (p = 0.004). Risk factors for mortality included requirements of higher levels of hemodynamic (61.1% vs. 17.5%, p = 0.001) and respiratory (88.9% vs. 37.5%, p < 0.001) support, and positive fungal cultures (p = 0.046). Conclusions: Familial HLH still represents a challenge in the pediatric critical care setting. Earlier diagnosis and prompt initiation of appropriate treatment could improve F-HLH survival.

Ostial stenosis of reimplanted left main coronary artery and supravalvular pulmonary stenosis: a case report of two complications of surgery for anomalous left coronary artery from the pulmonary artery.

Background: Anomalous origin of the coronary artery from the pulmonary artery (ALCAPA) is a rare congenital disease. Surgical re-implantation of the left main coronary artery (LMCA) to the aorta is a definitive treatment with a good prognosis. Case summary: A 9-year-old boy was admitted with a complaint of exertional chest pain and dyspnoea. At 13 months of age, he was diagnosed to have ALCAPA as a workup of severe left ventricular systolic dysfunction and underwent coronary re-implantation of ALCAPA. Coronary angiogram displayed the high takeoff of re-implanted LMCA with significant ostial stenosis, and echocardiogram showed significant supravalvular pulmonary stenosis (SVPS) with a peak gradient of 74 mmHg. After a multidisciplinary team discussion, he underwent percutaneous coronary intervention with stenting to ostial LMCA. On follow-up, he was asymptomatic and a cardiac computed tomography scan showed a patent stent in LMCA with an under-expanded area in the mid-segment. The proximal part of the LMCA stent was located very close to the stenotic segment of the main pulmonary artery making it a high risk for balloon angioplasty. The surgical intervention of SVPS is delayed to allow the somatic growth of the patient. Discussion: Percutaneous coronary intervention in re-implanted LMCA is a feasible option. If stenosis of re-implanted LMCA is accompanied by SVPS, the latter can be best treated surgically and staged to decrease the operative risk. Our case also demonstrates the importance of long-term follow-up of post-operative complications of patients with ALCAPA.

Optimized spirooxindole-pyrazole hybrids targeting the p53-MDM2 interplay induce apoptosis and synergize with doxorubicin in A549 cells.

Recently, cancer research protocols have introduced clinical-stage spirooxindole-based MDM2 inhibitors. However, several studies reported tumor resistance to the treatment. This directed efforts to invest in designing various combinatorial libraries of spirooxindoles. Herein, we introduce new series of spirooxindoles via hybridization of the chemically stable core spiro[3H-indole-3,2'-pyrrolidin]-2(1H)-one and the pyrazole motif inspired by lead pyrazole-based p53 activators, the MDM2 inhibitor BI-0252 and promising molecules previously reported by our group. Single crystal X-ray diffraction analysis confirmed the chemical identity of a representative derivative. Fifteen derivatives were screened for cytotoxic activities via MTT assay against a panel of four cancer cell lines expressing wild-type p53 (A2780, A549, HepG2) and mutant p53 (MDA-MB-453). The hits were 8h against A2780 (IC50 = 10.3 µM) and HepG2 (IC50 = 18.6 µM), 8m against A549 (IC50 = 17.7 µM), and 8k against MDA-MB-453 (IC50 = 21.4 µM). Further MTT experiments showed that 8h and 8j potentiated doxorubicin activity and reduced its IC50 by at least 25% in combinations. Western blot analysis demonstrated that 8k and 8m downmodulated MDM2 in A549 cells. Their possible binding mode with MDM2 were simulated by docking analysis.

A Case of Synchronous Multiple Primary Malignancies Involving Multiple Myeloma and Pharyngeal Plasmacytoma in an Elderly Male: A Case Report and Review of the Literature.

Monoclonal plasma cells form the solitary neoplasm known as solitary plasmacytoma. Isolated extramedullary plasmacytoma is less common than solitary bone plasmacytoma. An elderly male presented with coughing blood and was diagnosed with pharyngeal plasmacytoma with synchronous multiple myeloma. Herein, we present this challengingly rare case to increase awareness of this unusual entity.

Intraparotid Recurrence of Papillary Thyroid Carcinoma After Thyroidectomy Coincident With Declining Thyroglobulin Levels: A Case Report and Review of the Literature.

Papillary thyroid carcinoma (PTC) is the most frequent thyroid malignancy. Intraparotid recurrence of PTC is, however, rare. Most parotid malignancies are either primary or metastatic from cancer outside the head and neck. We report a case of a 71-year-old man who had undergone lobectomy and completion thyroidectomy for PTC and presented to our clinic with an insidious intraparotid recurrence, for which he underwent a superficial parotidectomy and radioactive iodine therapy. We also present a review of the literature on similar cases. Intraparotid metastasis of PTC should be considered in the differential diagnosis of a parotid mass.