The relation between Parkinson's disease and non-steroidal anti-inflammatories; a systematic review and meta-analysis.

Background: Parkinson's disease (PD) is a neurological condition that typically shows up with aging. It is characterized by generalized slowness of movement, resting tremor or stiffness, and bradykinesia. PD patients' brains mostly exhibit an increase in inflammatory mediators and microglial response. Nevertheless, a variety of non-steroidal anti-inflammatory medications (NSAIDS) offered neuroprotection in animal models and preclinical trials. Aim: The current systematic review and meta-analysis were designed to try to resolve the debate over the association of NSAID use with the development of PD because the results of several studies were somehow contradictory. Methods: An intense search was performed on Scopus, PubMed, and Web of Science databases for articles relating the incidence of PD to the use of NSAIDs. Statistical analysis of the included studies was carried out using Review Manager version 5.4.1 by random effect model. The outcome was identified as the development of PD in patients who were on NSAIDs, ibuprofen only, aspirin only, and non-aspirin NSAIDs. This was analyzed using pooled analysis of odds ratio (OR) at a significance level of ≤0.05 and a confidence level of 95%. A statistically significant decreased risk of PD was observed in patients taking NSAIDs, Ibuprofen, and non-aspirin NSAIDs. Results: The ORs of PD occurrence in patients who took NSAIDs, Ibuprofen, and non-aspirin NSAIDs were 0.88 [95% CI (0.8-0.97), p = 0.01], 0.73 [95% CI (0.53-1), p = 0.05] and 0.85 [95% CI (0.75-0.97), p = 0.01]. Meanwhile, the risk of PD in patients who took aspirin was not statistically significant. Conclusion: In conclusion, Ibuprofen, non-aspirin NSAIDs, and other types of NSAIDs could be associated with a reduction in PD risk. However, there was no association between aspirin intake and the development of PD.

Autoimmune Hemolytic Anemia Associated With Myelodysplastic Syndrome: A Case Report.

Myelodysplastic syndrome (MDS) represents a spectrum of myeloid disorders occasionally linked to autoimmune diseases. Here, we present a case of a 60-year-old man demonstrating an unusual coexistence of MDS with warm-autoantibody autoimmune hemolytic anemia (wAIHA). Diagnostic evaluation, including positive direct antiglobulin testing, confirmed the autoimmune etiology of his anemia despite his low-risk MDS classification. Prompt initiation of prednisone therapy resulted in significant hematological and clinical improvement, allowing for a conservative management approach without transfusion requirements. This case underscores the importance of identifying the relationship between wAIHA and MDS, particularly in low-risk scenarios. Moreover, these findings suggest the efficacy of corticosteroids in managing autoimmune anemia in the context of concomitant wAIHA and MDS.

Impact of previously failed extracorporeal shock wave lithotripsy on ureterorenoscopy outcomes in upper urinary tract stones: a prospective comparative study.

OBJECTIVE: We sought to prospectively evaluate the impact of previously failed SWL on subsequent URS outcomes in the treatment of upper urinary tract stones. MATERIALS AND METHODS: Between May 2021 and May 2023, one hundred thirty-six patients with proximal ureteral stones < 1.5 cm and renal stones < 2.5 cm who were candidates for URS were prospectively assigned to a non-SWL group, which included patients without a history of failed SWL before URS, and a post-SWL group, which included patients with a history of failed SWL before URS. The success rate was the primary outcome. The perioperative data of the two groups were compared. RESULTS: The stone-free rate was 83.3% in the post-SWL group versus 81.3% in the non-SWL group, and 8.3% in the post-SWL group versus 9.4% in the non-SWL group had clinically insignificant residual fragments. There was no significant difference in the stone-free rate or success rate between the groups. No significant differences in intraoperative fluoroscopy time, operative time, intraoperative stone appearance, perioperative complications, or the presence of embedded fragments in the ureteral mucosa were detected between the two groups. CONCLUSION: Compared with patients who underwent primary URS, patients who underwent salvage URS for upper urinary tract stones had similar stone-free rates, success rates, operative times, fluoroscopy times, and complication rates without any significant differences.

Mechanistic Insights of Neuroprotective Efficacy of Verapamil-Loaded Carbon Quantum Dots against LPS-Induced Neurotoxicity in Rats.

Alzheimer's disease (AD) is a neurodegenerative disease that badly impacts patients and their caregivers. AD is characterized by deposition of amyloid beta (Aß) and phosphorylated tau protein (pTau) in the brain with underlying neuroinflammation. We aimed to develop a neuroprotective paradigm by loading verapamil (VRH) into hyaluronic acid-modified carbon quantum dots (CQDs) and comparing its effectiveness with the free form in an AD-like model in rats induced by lipopolysaccharide (LPS). The experimental rats were divided into seven groups: control, LPS, CQDs, early free VRH (FVRH), late FVRH, early verapamil carbon quantum dots (VCQDs), and late VCQDs. Characterizations of VCQDs, the behavioral performance of the rats, histopathological and immunohistochemical changes, some AD hallmarks, oxidative stress biomarkers, neuro-affecting genes, and DNA fragmentation were determined. VRH was successfully loaded into CQDs, which was confirmed by the measured parameters. VRH showed enhancement in cognitive functions, disruption to the architecture of the brain, decreased Aß and pTau, increased antioxidant capacity, modifiable expression of genes, and a decline in DNA fragmentation. The loaded therapy was superior to the free drug. Moreover, the early intervention was better than the late, confirming the implication of the detected molecular targets in the development of AD. VRH showed multifaceted mechanisms in combating LPS-induced neurotoxicity through its anti-inflammatory and antioxidant properties, thereby mitigating the hallmarks of AD. Additionally, the synthesized nanosystem approach exhibited superior neuroprotection owing to the advantages offered by CQDs. However, finding new actionable biomarkers and molecular targets is of decisive importance to improve the outcomes for patients with AD.

Enhanced neuroprotective effect of verapamil-loaded hyaluronic acid modified carbon quantum dots in an in-vitro model of amyloid-induced Alzheimer's disease.

This study aims to investigate the molecular mechanisms and the neuroprotective effect of hyaluronic acid modified verapamil-loaded carbon quantum dots (VRH-loaded HA-CQDs) against an in-vitro Alzheimer's disease model induced by amyloid beta (Aß) in SH-SY5Y and Neuro 2a neuroblastoma cells. Briefly, different HA-CQDs were prepared using hydrothermal method and optimized by Box-Behnken design to maximize quantum yield and minimize particle size. Serum stable negatively charged VRH-loaded HA-CQDs was successfully prepared by admixing the optimized HA-CQDs and VRH with association efficiency and loading capacity of 81.25 ± 3.65 % and 5.11 ± 0.81 %, respectively. Cells were pretreated with VRH solution or loaded-HA-CQDs followed by exposure to Aß. Compared to the control group, amyloidosis led to reduction in cellular proliferation, mitochondrial membrane potential, expression of cytochrome P450, cytochrome c oxidase, CREB-regulated transcriptional coactivator 3, and mitotic index, along with marked increase in reactive oxygen species (ROS) and inflammatory cytokines. Pretreatment with VRH, either free or loaded HA-CQDs, enhanced cell survival, mitochondrial membrane potential, mitotic index, and gene expression. It also reduced inflammation and ROS. However, VRH-loaded HA-CQDs exhibited superior effectiveness in the measured parameters. These findings suggest that VRH-loaded HA-CQDs have enhanced therapeutic potential compared to free VRH in mitigating amyloidosis negative features.

Effect of a high dose atorvastatin as added-on therapy on symptoms and serum AMPK/NLRP3 inflammasome and IL-6/STAT3 axes in patients with major depressive disorder: randomized controlled clinical study.

Background: Neuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression. Aim: To investigate the mechanistic pathways of high dose atorvastatin in MDD. Patients and methods: This trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS<17 and>7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured. Results: The atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine (p = 0.03, and p = 0.005), respectively. Conclusion: These results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/NLRP3 and IL-6/STAT-3. Clinical Trial Registration: clinicaltrials.gov, identifier NCT05792540.

Evaluation of the Effect of Loratadine versus Diosmin/Hesperidin Combination on Vinca Alkaloids-Induced Neuropathy: A Randomized Controlled Clinical Trial.

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group-neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response.

Acute Non-infectious Cystitis Secondary to Immune-Related Adverse Events in a Patient Receiving Pembrolizumab for Treatment of Non-small Cell Lung Cancer: A Case Report.

Immune-related adverse events (IrAEs) involving the bladder are seldom reported and tend to be overlooked by oncologists. Cystitis caused by immune checkpoint inhibitors (ICIs) is rarely reported, with only four documented instances in the literature, of which just one case is attributed to pembrolizumab. We present a rare occurrence of pembrolizumab-induced hemorrhagic cystitis in a 71-year-old male with stage II-b lung adenocarcinoma with an chronic indwelling Foley catheter. He presented with persistent hematuria despite the completion of a course of antibiotics for a urinary infection; a cystoscopic examination was also normal. Drug-induced cystitis was suspected and the patient was treated with prednisone as well as temporary discontinuation of pembrolizumab, which was followed by an improvement of symptoms.

Anaplastic Large Cell Lymphoma (ALCL) With a Sarcomatoid Variant Presenting As Distributive Shock in a 41-Year-Old Female: A Case Report.

The sarcomatoid variant is considered a rare subtype of anaplastic large cell lymphoma. We present a 40-year-old diabetic female who was evaluated in the ER for distributive shock, requiring vasopressors and mechanical ventilation. An extensive workup was negative for infection. A serial CT scan of the abdomen and pelvis showed evolving lymphadenopathy, and a biopsy revealed malignant anaplastic lymphoma cells with a sarcomatous variant. The oncology team recommended the initiation of inpatient chemotherapy; however, the family opted to proceed with comfort care measures.

Efficiency of Near-Infrared Technology in the Clinical Detection of Carious Lesions: A Systematic Review.

The field of dentistry has seen various technological advances regarding caries detection, some lesions still prove to be difficult to detect. A reasonably new detection method, near-infrared (NIR), has shown good results in caries detection. This systematic review aims to compare NIR with conventional methods in terms of caries detection. Online databases (PubMed, Scopus, ScienceDirect, EBSCO, and ProQuest) were used for the literature search. The search was performed from January 2015 till December-2020. A total of 770 articles were selected, of that 17 articles qualified for the final analysis as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The articles were assessed according to a modified Critical Appraisal Skills Programme checklist, and then synthesis of the review started. The inclusion criteria were clinical trials done in vivo on teeth with active caries of vital or nonvital teeth. This review excluded nonpeer reviewed articles, case reports, case series, opinions, abstracts, non-English written articles, studies of subjects with arrested caries, or teeth with developmental defects of tooth structure and teeth having environmental defects of tooth structure, as well as in-vitro studies. The review compared near-infrared technology with radiography, visual inspection, and laser fluorescence in terms of caries detection, sensitivity, specificity, and accuracy. The sensitivity of NIR ranged from 99.1 to 29.1%. Studies showed that NIR exhibited higher sensitivity for occlusal enamel and dentin caries. The specificity of NIR ranged from 94.1 to 20.0%. In enamel and dentinal occlusal caries, NIR demonstrated lower specificity than that of radiograph. The specificity of NIR in early proximal caries was low. Accuracy was determined in 5 out of 17 studies where the values ranged from 97.1 to 29.1%. The accuracy of NIR was the highest for dentinal occlusal caries. NIR shows promising evidence as an adjunct in caries examination due to its high sensitivity and specificity; however, more studies are required to determine its full potential in different situations.

The Potential Role of Circulating Long Miscellaneous RNAs in the Diagnosis and Prognosis of Hepatitis C Related Hepatocellular Carcinoma.

Ribonucleic acids (RNAs) are important regulators of gene expression and crucial for the progression of hepatocellular carcinoma (HCC). This study was designed to determine the diagnostic and prognostic utility of the circulating long miscellaneous RNAs; LINC01419, AK021443, and AF070632 in HCV-related HCC patients. Real-time PCR was used to measure their relative expression levels in the plasma of 194 HCV patients, 120 HCV-related HCC patients and 120 healthy controls. LINC01419 and AK021443 expression levels had significantly increasing linear trend estimates while AF070632 was dramatically downregulated in HCC compared to HCV. Interestingly, LINC01419 and AK021443 served as more significant diagnostic biomarkers for HCC than AF070632 and AFP. Multivariate analysis with cox regression revealed that the high expression of AK021443 [HR = 10.06, CI95%: 3.36-30.07], the high expression of LINC01419 [HR 4.13, CI95%: 1.32-12.86], and the low expression of AF070632 [HR = 2.70, CI95%: 1.07-6.81] were significant potential prognostic factors for HCC. Besides, the Kaplan-Meier analysis showed that HCC patients with high LIN01419 and AK021443 and low AF070632 expression levels had shorter OS. The circulating LINC01419 and AK021443 can be used as noninvasive potential biomarkers for diagnosis and prognosis of HCV-related HCC patients than AF070632 providing new targets for limiting the progression of the disease.

The Potential Neuroprotective Effect of Thymoquinone on Scopolamine-Induced In Vivo Alzheimer's Disease-like Condition: Mechanistic Insights.

BACKGROUND: Alzheimer's disease (AD) is a common neurodegenerative disorder without effective treatment. Thymoquinone (TQ) has demonstrated potential in exhibiting anti-inflammatory, anti-cancer, and antioxidant characteristics. Despite TQ's neuroprotection effect, there is a scarcity of information regarding its application in AD research, and its molecular trajectories remain ambiguous. Thus, the objective of the current investigation was to examine the potential beneficial effects and underlying mechanisms of TQ in scopolamine (SCOP)-induced neuronal injury to mimic AD in vivo model. METHODS: Thirty mice were divided into normal, SCOP, and TQ groups. The Y-maze and pole climbing tests were performed to measure memory and motor performance. Afterwards, histopathological and immunohistochemical examinations were carried out. Furthermore, peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway-related proteins and genes were detected with an emphasis on the role of miR-9. RESULTS: TQ has the potential to ameliorate cognitive deficits observed in SCOP-induced AD-like model, as evidenced by the improvement in behavioral outcomes, histopathological changes, modulation of the expression pattern of PPAR-γ downstream targets with a significant decrease in the deposition of amyloid beta (Aß). CONCLUSIONS: TQ provided meaningful multilevel neuroprotection through its anti-inflammatory and its PPAR-γ agonist activity. Consequently, TQ may possess a potential beneficial role against AD development.

Effects of early adjunctive pharmacotherapy on serum levels of brain injury biomarkers in patients with traumatic brain injury: a systematic review of randomized controlled studies.

Objectives: Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the effectiveness of adjuvant neuroprotective treatments in terms of their effect on brain injury biomarkers in TBI patients. Methods: To identify relevant studies, four scholarly databases, including PubMed, Cochrane, Scopus, and Google Scholar, were systematically searched using predefined search terms. English-language randomized controlled clinical trials reporting changes in brain injury biomarkers, namely, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1) and/or S100 beta (S100 ß), were included. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. Results: A total of eleven studies with eight different therapeutic options were investigated; of them, tetracyclines, metformin, and memantine were discovered to be promising choices that could improve neurological outcomes in TBI patients. The most utilized serum biomarkers were NSE and S100 ß followed by GFAP, while none of the included studies quantified UCHL1. The heterogeneity in injury severity categories and measurement timing may affect the overall evaluation of the clinical efficacy of potential therapies. Therefore, unified measurement protocols are highly warranted to inform clinical decisions. Conclusion: Few therapeutic options showed promising results as an adjuvant to standard care in patients with TBI. Several considerations for future work must be directed towards standardizing monitoring biomarkers. Investigating the pharmacotherapy effectiveness using a multimodal biomarker panel is needed. Finally, employing stratified randomization in future clinical trials concerning potential confounders, including age, trauma severity levels, and type, is crucial to inform clinical decisions. Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/dis], identifier [CRD42022316327].

Evaluating the safety and efficacy of the leukotriene receptor antagonist montelukast as adjuvant therapy in obese patients with type 2 diabetes mellitus: A double-blind, randomized, placebo-controlled trial.

Background: Type 2 diabetes mellitus (T2DM) is common with obesity. Metformin is a first-line therapy for this condition. However, it has only a minor impact on weight loss in some patients. Aim: This study aimed to evaluate the effectiveness, tolerability, and safety of combining montelukast therapy with metformin in obese diabetic patients. Methods: One hundred obese diabetic adult patients were recruited and randomized into two equal groups. Group 1 received placebo plus metformin 2 g/d, and Group 2 received 2 g/d metformin plus 10 mg/d montelukast. Demographic, anthropometric measurements (e.g., body weight, body mass index [BMI], and visceral adiposity index), lipid profile, diabetes control measures (fasting blood glucose, glycated hemoglobin [HbA1c], and homeostatic model assessment for insulin resistance [HOMA-IR]), adiponectin, and inflammatory markers (e.g., TNF-α, IL-6, and leukotriene B4) were assessed and reported for each group at baseline and after 12 weeks of treatment. Results: Both interventions significantly reduced all the measured parameters, except for adiponectin and HDL-C, levels of which increased compared to baseline data (p < 0.001). The montelukast group significantly improved in all parameters compared to the placebo group (ANCOVA test p < 0.001). The percentage changes in BMI, HbA1c, HOMA-IR, and inflammatory markers were 5%, 9%, 41%, and 5%-30%, respectively, in the placebo group compared to 8%, 16%, 58%, and 50%-70%, respectively, in the montelukast group. Conclusion: Montelukast adjuvant therapy was superior to metformin-only therapy in diabetes control and weight loss, most likely due to its increased insulin sensitivity and anti-inflammatory properties. The combination was tolerable and safe throughout the study duration. Clinical Trial Registration: [Clinicaltrial.gov], identifier [NCT04075110].

A Rare Case Presentation of Vitiligo Associated With Atezolizumab.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies used in the treatment of solid and hematologic malignancies. Immune checkpoint inhibitors target the T-cell deactivation system via the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) receptor, programmed cell death protein 1 (PD-1) receptor, and programmed cell death ligand 1 (PD-L1). As a result, the activated T-cell enhances the host tumor response. However, even with their essential clinical benefits, ICIs are associated with a broad spectrum of adverse effects that can be generalized or tissue-specific inflammatory responses known as immune-related adverse events (irAEs). The most common dermatologic toxicity manifests mainly as maculopapular rash and pruritus. Understanding the complexity of immune-mediated response and the importance of clinical histopathologic correlation in recognizing irAEs allows for appropriate intervention and patient care due. We present the case of a 71-year-old African American male diagnosed with a large-cell poorly differentiated neuroendocrine tumor in the gastroesophageal junction of the stomach with mediastinal lymphadenopathy. He was treated with carboplatin, etoposide, and atezolizumab for 4 cycles. However, he developed vitiligo while on maintenance atezolizumab, which is rarely seen with atezolizumab use. Despite the improving clinical outcomes in oncology with ICIs, their adverse effects should not be ignored. When promptly recognized and treated, patients on ICI monotherapy may not need treatment interruption or discontinuation.

Pentoxifylline as an adjunctive in treatment of negative symptoms in chronic schizophrenia: A double-blind, randomized, placebo-controlled trial.

AIM: The aim of this study was to explore the effectiveness and safety of pentoxifylline as an adjuvant to risperidone in mitigating the negative symptoms in patients with chronic schizophrenia. METHODS: In this randomized, placebo-controlled study, eighty outpatients with chronic schizophrenia were given risperidone for 8 weeks along with either pentoxifylline or a placebo. The positive and negative syndrome scale (PANSS) was used to assess patients at the start of the trial, as well as at 2, 4, 6, and 8 weeks. Pre- and posttreatment serum levels of cAMP, TNF-α-, and IL-6 were measured. RESULTS: The pentoxifylline group revealed a significant effect for time-treatment interaction on PANSS-negative subscale scores (p < 0.001), PANSS general psychopathology subscale scores (p < 0.001), and PANSS total scores (p < 0.001), but not on PANSS-positive subscale scores (p = 0.169). Additionally, when compared to the placebo group, the pentoxifylline group demonstrated a statistically significant increase in cAMP serum level and a statistically significant decrease in TNF-α and IL-6 serum levels. CONCLUSION: Pentoxifylline adjunctive therapy with risperidone for 8 weeks was found to be promising in mitigating the negative symptoms in patients with chronic schizophrenia. TRIAL REGISTRATION NUMBER: NCT04094207.

A Rare Presentation of Small Bowel Perforation Secondary to Microscopic Metastasis of Non-small Cell Lung Cancer (NSCLC): A Case Report.

Gastrointestinal tract perforation (GITP) due to metastatic lung cancer is an exceptionally rare occurrence. Symptoms can range from mild abdominal discomfort to severe and life-threatening bowel perforation. In this case presentation, we describe an unusual instance involving squamous non-small cell lung cancer (NSCLC), where microscopic metastases in the small bowel led to bowel perforation. Our patient, a 71-year-old male with a history of stage IIIa squamous cell carcinoma in the right lung and smoking history, completed chemoradiation therapy and is currently undergoing treatment with durvalumab. He presented to the ED with complaints of abdominal pain, nausea, and abdominal distention. His review of systems revealed no other significant issues, and his vital signs were stable. However, the abdominal examination revealed noticeable distention with tenderness upon palpation and guarding. Laboratory results were significant for leukocytosis with a left shift of neutrophils and mildly elevated kidney function. A CT scan of the abdomen and pelvis revealed widespread pneumoperitoneum, indicating a bowel perforation. Consequently, the patient underwent an urgent exploratory laparotomy, during which a small bowel perforation measuring 0.6 cm x 0.3 cm in the jejunum was identified, necessitating the resection of the affected bowel segment. Intraoperative esophagogastroduodenoscopy (EGD) showed normal findings. The histopathological examination of the resected bowel revealed clusters of squamous cell carcinoma with a desmoplastic reaction, affecting the submucosal and muscular layers at the site of the defect, with surgical margins free of tumor or inflammation. This finding indicated metastatic disease originating from the known lung squamous cell carcinoma. After the operation, the patient was admitted to the ICU due to septic shock caused by E. coli and Klebsiella peritonitis, requiring intubation and circulatory support with pressors. Ultimately, he was discharged following treatment. This case underscores the rarity of symptomatic bowel perforation from micro-metastasis in squamous NSCLC and emphasizes the need for rigorous assessment and timely surgical intervention. However, it is important to recognize the significant risk of complications and a high mortality rate, leading to a challenging prognosis. As such, individuals with a known history of lung carcinoma who present with abdominal symptoms should undergo comprehensive evaluation to prevent life-threatening complications through early intervention.

Chronotherapeutic neuroprotective effect of verapamil against lipopolysaccharide-induced neuroinflammation in mice through modulation of calcium-dependent genes.

BACKGROUND: Neuroinflammation is a major mechanism in neurodegenerative diseases such as Alzheimer's disease (AD), which is a major healthcare problem. Notwithstanding of ample researches figured out possible molecular mechanisms underlying the pathophysiology of AD, there is no definitive therapeutics that aid in neuroprotection. Therefore, searching for new agents and potential targets is a critical demand. We aimed to investigate the neuroprotective effect of verapamil (VRP) against lipopolysaccharide (LPS)-induced neuroinflammation in mice and whether the time of VRP administration could affect its efficacy. METHODS: Forty male albino mice were used and were divided into normal control, LPS only, morning VRP, and evening VRP. Y-maze and pole climbing test were performed as behavioral tests. Hematoxylin and eosin together with Bielschowsky silver staining were done to visualize neuroinflammation and phosphorylated tau protein (pTAU); respectively. Additionally, the state of mitochondria, the levels of microglia-activation markers, inflammatory cytokines, intracellular Ca2+, pTAU, and Ca2+-dependent genes involving Ca2+/ calmodulin dependent kinase II (CAMKII) isoforms, protein kinase A (PKA), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF), with the level of VRP in the brain tissue were measured. RESULTS: LPS successfully induced neuroinflammation and hyperphosphorylation of tau protein, which was indicated by elevated levels of microglia markers, inflammatory cytokines, and intracellular Ca2+ with compromised mitochondria and downregulated CAMKII isoforms, PKA, CREB and BDNF. Pretreatment with VRP showed significant enhancement in the architecture of the brain and in the behavioral tests as indicated by the measured parameters. Moreover, morning VRP exhibited better neuroprotective profile compared to the evening therapy. CONCLUSIONS: VRP highlighted a multilevel of neuroprotection through anti-inflammatory activity, Ca2+ blockage, and regulation of Ca2+-dependent genes. Furthermore, chronotherapy of VRP administration should be consider to achieve best therapeutic efficacy.

The clinicopathological and prognostic factors of hepatocellular carcinoma: a 10-year tertiary center experience in Egypt.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major health problem despite the emergence of several preventive and therapeutic modalities. HCC has heterogeneous and wide morpho-molecular patterns, resulting in unique clinical and prognostic criteria. Therefore, we aimed to study the clinical and pathological criteria of HCC to update the morpho-molecular classifications and provide a guide to the diagnosis of this disease. METHODS: Five hundred thirty pathologically analyzed HCC cases were included in this study. The clinical and survival data of these cases were collected. RESULTS: Hepatitis C virus is still the dominant cause of HCC in Egypt. Post-direct-acting antiviral agent HCC showed an aggressive course compared to interferon-related HCC. Old age, male gender, elevated alpha-fetoprotein level, tumor size, and background liver were important prognostic parameters. Special HCC variants have characteristic clinical, laboratory, radiological, prognostic, and survival data. Tumor-infiltrating lymphocytes rather than neutrophil-rich HCC have an excellent prognosis. CONCLUSIONS: HCC is a heterogenous tumor with diverse clinical, pathological, and prognostic parameters. Incorporating the clinicopathological profile per specific subtype is essential in the treatment decision of patients with HCC. TRIAL REGISTRATION: This was a retrospective study that included 530 HCC cases eligible for analysis. The cases were obtained from the archives of the Pathology Department, during the period between January 2010 and December 2019. Clinical and survival data were collected from the patients' medical records after approval by the institutional review board (IRB No. 246/2021) of Liver National Institute, Menoufia University. The research followed the guidelines outlined in the Declaration of Helsinki and registered on ClinicalTrials.gov (NCT05047146).