Discrepancies in Gleason score between needle core biopsy and radical prostatectomy specimens with correlation between clinical and pathological staging.

BACKGROUND: The studies have shown that GS given after assessment of the entire prostate gland on the radical prostatectomy specimen may differ from GS given after examination of a small sample from needle core biopsy. We conducted this study to assess discrepancies in the Gleason score between NCB and RP specimens and to find out the correlation between the clinical stage and pathological stage. METHODS: The study included 174 patients with carcinoma prostate which underwent robotic-assisted radical prostatectomy (RARP). Pre-operative Gleason score was determined on 12-core biopsy samples under trans-rectal ultrasound (TRUS) guidance. The Gleason score obtained from the radical prostatectomy specimen was compared with that of the NCB Gleason score to find out differences. RESULTS: The preoperative Gleason score (GS) ranges from 6 to 9 with a mean GS of 6.97 ± 1.02. The post-operative GS ranges between 6 and 10 with mean and GS of 7.5 ± 1.10. On the pre-operative assessment of biopsy specimens, 70 (43.2%) patients had a GS of 6, while 44 patients had a GS of 7 (27.1%) and 48 (29.8%) patients had a GS of more than 7. On the postoperative assessment of specimens, 31 (19.1%) patients had post-operative GS of 6, while 66 (41%) patients had GS of 7 and 74 (41.1%) patients had GS of more than 7. When pre-operative GS and post-operative GS were compared, no changes were observed in the GS of 79 patients, whereas 83 patients showed the difference in GS, with 75 patients showing up-gradation and eight patients marked as down-graded. CONCLUSION: concordance between biopsy and the pathology results directly affects the prognosis of the patient. The results of our study demonstrated the rate of discordance between Gleason scores obtained from transrectal prostate biopsy and RP surgical specimens. This rate brings into question the accuracy of the chosen treatment.

Cerebrospinal fluid protein biomarkers in Parkinson's disease.

Proteomic profiling is an effective way to identify biomarkers for Parkinson's disease (PD). Cerebrospinal fluid (CSF) has direct connectivity with the brain and could be a source of finding biomarkers and their clinical implications. Comparative proteomic profiling has shown that a group of differentially displayed proteins exist. The studies performed using conventional and classical tools also supported the occurrence of these proteins. Many studies have highlighted the potential of CSF proteomic profiling for biomarker identification and their clinical applications. Some of these proteins are useful for disease diagnosis and prediction. Proteomic profiling of CSF also has immense potential to distinguish PD from similar neurodegenerative disorders. A few protein biomarkers help in fundamental knowledge generation and clinical interpretation. However, the specific biomarker of PD is not yet known. The use of proteomic approaches in clinical settings is also rare. A large-scale, multi-centric, multi-population and multi-continental study using multiple proteomic tools is warranted. Such a study can provide valuable, comprehensive and reliable information for a better understanding of PD and the development of specific biomarkers. The current article sheds light on the role of CSF proteomic profiling in identifying biomarkers of PD and their clinical implications. The article also explains the achievements, obstacles and hopes for future directions of this approach.

Robot-assisted ureteric reconstructive surgeries for benign diseases: Initial single-center experience with point of technique.

INTRODUCTION: We present our initial experience with robot-assisted reconstructive surgeries with the Da Vinci Xi robotic system for benign ureteric pathologies. MATERIALS AND METHODS: This is a retrospective review of prospectively collected data of patients who underwent robot-assisted reconstructive procedures for benign diseases of the ureter at our department from April 2018 to November 2022. Demographic and perioperative details were recorded. Patients were followed up and surgical success was evaluated on the basis of symptomatic, functional, and radiological improvement. RESULTS: A total of 34 patients underwent robot-assisted reconstructions for benign ureteric pathologies by various techniques. Mean age, body mass index (BMI), hospital stay and follow-up duration were 36 years, 24.1 kg/m2, 5.29 days, and 7.08 months respectively. Procedures included pyeloplasty in eight, primary ureteroneocystostomy (UNC) in seven, Psoas hitch UNC in five, Boari flap UNC in six, Ureteroureterostomy in four, ureterocalicostomy in two and ileal ureteral transposition in two patients. Mean docking time, total operative time, and estimated blood loss were 31.5 min, 178 min, and 64.3 ml, respectively. All patients had radiologic or functional improvement on follow-up after 6 months. CONCLUSION: Robot-assisted reconstructive surgery for benign ureteric and bladder pathologies imparted excellent short-term outcomes without major complications with all the advantages of a minimally invasive approach.

Incidental detection of rare vascular variation during pyeloplasty and its clinical implication - A case report.

ABSTRACT: Crossing vessels is one of the important causes of pelviureteric junction obstruction (PUJO). Accessory lower polar vessels are commonly seen with congenital PUJO, but they are not always the cause of obstruction. We incidentally encountered a variation in the lower polar crossing vessel while doing laparoscopic pyeloplasty in a patient with congenital PUJO. We encountered a right accessory lower polar artery and vein along with a right gonadal artery arising from the accessory right renal artery and right gonadal vein draining into the right lower polar crossing accessory renal vein. Knowledge of variations in genitourinary vasculature is important in the current era to prevent inadvertent complications.

Early port site and peritoneal metastasis following robot-assisted radical cystectomy: a rare case report.

Radical cystectomy with pelvic lymph node dissection is the recommended treatment for managing muscle-invasive carcinoma of the urinary bladder. Early recurrence is observed in only about 4.1% of cases. Port-site metastasis following robot-assisted radical cystectomy is extremely rare. We encountered a challenging and a rare case of bladder cancer that manifested with port-site and peritoneal metastasis within 6 weeks of surgery.

TPGS-modified Chitosan Nanoparticles of EGFR Inhibitor: Physicochemical and In vitro Evaluation against HepG2 Cell Lines.

BACKGROUND: Gefitinib (GFN) is an Epithelial Growth Factor Receptor (EGFR) inhibitor, and Food and Drug Administration (FDA) has approved medication to treat lung cancer. However, this investigation aimed to produce and characterize Gefitinib (GFN)-loaded chitosan and soy lecithin nanoparticles (NPs) modified with D-α-tocopheryl polyethylene glycol 1000 succinate mono ester (TPGS) and assess their therapeutic potential against HepG2 liver cell lines. METHODS: Chitosan, a cationic polymer with biocompatible and biodegradable properties, was combined with soy lecithin to develop the NPs loaded with GFN using a self-organizing ionic interaction methodology. RESULTS: The entrapment efficiency and drug loading were found to be 59.04±4.63 to 87.37±3.82% and 33.46±3.76 to 49.50±4.35%, respectively, and results indicated the encapsulation of GEN in NPs. The pH of the formulations was observed between 4.48-4.62. Additionally, all the prepared NPs showed the size and PDI range of 89.2±15.9 nm to 799.2±35.8 nm and 0.179±0.065 to 0.455±0.097, respectively. The FTIR bands in optimized formulation (GFN-NP1) indicated that the drug might be contained within the NP's core. The SEM photograph revealed the spherical shape of NPs. The kinetic release model demonstrated the combination of diffusion and erosion mechanisms. The IC50 value of GFN and GFN-NP1 formulation against the HepG2 cell lines were determined and found to be 63.22±3.36 µg/ml and 45.80±2.53 µg/ml, respectively. DAPI and PI staining agents were used to detect nuclear morphology. CONCLUSION: It was observed that the optimized GFN-NP1 formulation successfully internalized and inhibited the growth of HepG2 cells. Hence, it can be concluded that the prepared NPs can be a new therapeutic option for treating liver cancer.

The Extent of Delay in Diagnosis, Treatment and their Associated Factors among Tuberculosis Patients Attending Government Hospitals of Rishikesh, Uttarakhand: A Cross-Sectional Study.

BACKGROUND: "Tuberculosis (TB) remains a major public health problem" worldwide, affecting almost all age groups. "Early diagnosis and prompt treatment are essential to significantly reducing the TB burden." However, a significant proportion of cases remain undiagnosed and untreated, which plays a vital role in the transmission of the disease and severity of the illness in the community in most developing countries. AIMS & OBJECTIVES: This study aimed to assess "the extent of delay in diagnosis and treatment of TB patients" and to identify the major factors associated with such delays (whether patient or health system-related) among TB patients in Rishikesh. METHODS: This descriptive cross-sectional study was conducted in Rishikesh Town, Dehradun District, Uttara khand, India. Total of 130 newly diagnosed TB patients were recruited as study participants who attended the government hospitals of Rishikesh, All India Institute of Medical Sciences, Rishikesh and S P S Government Hospital, Rishikesh. A universal sampling technique was used in this study. RESULTS: The mean age of the study participant was 36.75 (Standard Deviation (SD), 17.6), and the median age was 34 years. Of the patients, 64.6% were men, and 35.4% were women. The extent of various delays, such as patient delay (median 16 days), diagnostic delay (median 78.5 days), treatment delay (median 4 days), health system delay (43 days), and total delay (median 81 days). CONCLUSION: The misconception of any chronic disease may lead to a false diagnosis or long treatment for symptomatic relief; the absence of proper diagnostic tests and doctor shopping could be the reasons for the prolonged diagnostic delay. Therefore, by strengthening the collaboration between private and public practitioners in order to meet the expectations of the Government of India to achieve the goals of the "National Strategic Plan for ending TB" in India by providing good quality care for all patients.

A Complex Interplay of DJ-1, LRRK2, and Nrf2 in the Regulation of Mitochondrial Function in Cypermethrin-Induced Parkinsonism.

Cypermethrin impairs mitochondrial function, induces redox imbalance, and leads to Parkinsonism in experimental animals. Knockdown of deglycase-1 (DJ-1) gene, which encodes a redox-sensitive antioxidant protein, aggravates cypermethrin-mediated α-synuclein overexpression and oxidative alteration of proteins. DJ-1 is also reported to be essential for maintaining stability of nuclear factor erythroid 2-related factor 2 (Nrf2), shielding cells against oxidative insult. Leucine-rich repeat kinase 2 (LRRK2), another protein associated with Parkinson's disease, is also involved in regulating mitochondrial function. However, underlying molecular mechanisms remain elusive. The study intended to explore an interaction of DJ-1, LRRK2, and Nrf2 in the regulation of mitochondrial function in cypermethrin-induced Parkinsonism. Small interfering RNA-mediated knockdown of DJ-1 and LRRK2 gene and pharmacological activation of Nrf2 were performed in rats and/or human neuroblastoma cells with or without cypermethrin. Indexes of oxidative stress, mitochondrial impairment, and Parkinsonism along with α-synuclein expression, post-translational modification, and aggregation were measured. DJ-1 gene knockdown exacerbated cypermethrin-induced increase in oxidative stress and intrinsic apoptosis and reduction in expression of mitochondrial antioxidant proteins via inhibiting nuclear translocation of Nrf2. Additionally, cypermethrin-induced oxidative stress, mitochondrial impairment, and α-synuclein expression and aggregation were found to be suppressed by LRRK2 gene knockdown, by promoting Nrf2 nuclear translocation and expression of mitochondrial antioxidant proteins. Furthermore, Nrf2 activator, sulforaphane, ameliorated cypermethrin-induced mitochondrial impairment and oxidative stress and provided protection against dopaminergic neuronal death. The findings indicate that DJ-1 and LRRK2 independently alter Nrf2-mediated changes and a complex interplay among DJ-1, LRRK2, and Nrf2 exists in the regulation of mitochondrial function in cypermethrin-induced Parkinsonism.