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.

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.

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.

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.

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.

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.

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.