Chronic pain following a Lichtenstein inguinal hernia repair: a clinical and legal dilemma

Background: Chronic pain following a Lichtenstein inguinal hernia is frequent and raises major concerns regarding informed consent recall Objective: To assess the frequency of chronic pain and associated factors following inguinal hernia repair in a district general hospital. To assess patient recall of the consent process as it pertains to chronic pain. Methods: A random sample (170/293 patients) of those who underwent a Lichtenstein inguinal hernia repair between 2002 and 2004 were retrospectively assessed for the frequency, intensity and other co‐factors of chronic pain. They were also questioned about their recollection of the consent process and information given regarding chronic pain. Results: 50 percent of patients reported chronic pain at a median follow‐up of 62 months with 30% reporting a significant impact on daily activities. Younger age, the absence of a lump at presentation, pre‐operative pain and elective repair were the only factors significantly shown to increase the likelihood of post‐operative pain. Patients with post‐operative pain were significantly more likely to report that they had not been informed of the possibility of chronic pain pre‐operatively or at the time of consent. Twenty percent of these patients stated that they would not have undergone the operation if they had been informed of the possibility of chronic pain. Conclusion: Chronic pain is frequent and debilitating. Documentation of chronic pain as a possible outcome at the time of consent should be mandatory as patient recall is poor.     

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

Glycyrrhetinic acid is an active triterpenoid metabolite of glycyrrhizin abundantly present in licorice roots. Glycyrrhetinic acid exists as α and β stereo-isomeric forms. Both stereo-isomeric forms are known to have anti-inflammatory and anticancer activity. However, the effects and anticancer mechanism of α glycyrrhetinic acid in prostate cancer cells has not yet been evaluated. Therefore, we investigated the growth inhibition, induction of apoptosis and the anticancer mechanisms of 18α-glycyrrhetinic acid (AGA), on the androgen-independent metastatic prostate cancer cell line DU-145. Our results showed that AGA inhibited proliferation and growth of these cells by inducing apoptosis as determined by Annexin V and flow cytometry analyses. Our studies also showed that HUVEC tube formation was drastically reduced when cultured in conditioned medium of AGA-treated DU-145 cells. In addition, AGA treatment prevented the invasion of DU-145 prostate cancer cells on matrigel coated transwells via down-regulation of NF-κB (p65), VEGF and MMP-9 expression. Furthermore, AGA treatment also down-regulated the expression of pro-inflammatory cytokine/growth factor genes HMGB1, IL-6 and IL-8 in DU-145 cells. Interestingly, AGA simultaneously upregulated the expression of non-steroidal anti-inflammatory gene-1 (NAG-1) in DU-145 cells suggesting its anti-inflammatory activity on prostate cancer cells. Taken together, the results of this study suggest that AGA may be a promising anticancer agent that merits further investigation for the chemoprevention and treatment of prostate cancer.     

Pharmacokinetic/pharmacodynamic profiling of imipenem in patients admitted to an intensive care unit in India: A nonrandomized,cross-sectional,analytical, open-labeled study

Results:The difference in the plasma imipenem concentration between the gastrointestinal and the nongastrointestinal groups was significant at 2 h (P = 0.015) following drug dosing; while the difference was significant between the skin/cellulitis and nonskin/cellulitus groups at 2 h (P = 0.008), after drug dosing. The imipenem levels were above the MIC and 5 times the MIC for the isolated organism in 96.67% and 50% of the patients, respectively.Conclusions:The pharmacokinetic profile of imipenem does not vary according to the locus of an infection in critically ill patients. Imipenem, 3 g/day intermittent dosing, maintains a plasma concentration which is adequate to treat most infections encountered in patients admitted to an ICU. However, a change in the dosing regimen is suggested for patients infected with organisms having MIC values above 4 mg/L.     

Point-of-care renal ultrasound: the SECONDS checklist

Clinical and Experimental Nephrology -     

Impact of COVID 19 pandemic on patients requiring renal biopsy

Introduction

The disruption of healthcare services in coronavirus disease (COVID)19 pandemic was widespread particularly due to lockdown curbs. This study was undertaken to see the effect of this pandemic on subjects requiring renal biopsy.

Materials and method

Renal biopsies performed during the COVID 19 pandemic between April 2020 and December 2020 (Group 1) were compared with those in pre-COVID period between June 2019 and February 2020 (Group 2). Indication of biopsies, syndromic diagnosis and all baseline laboratory characteristics were retrieved from the hospital records.

Results

130 and 191 patients were biopsied in groups 1 and 2, respectively. Patients in group 1 were younger compared with group 2 (32.55?±?15.60 and 36.37?±?16.96 years, respectively, p value 0.038). The mean serum creatinine value in group 1 was significantly higher than in group 2 (3.21?±?2.08 and 2.68?±?2.02 mg/dl respectively, p value: 0.023). Group 1 comprises a significantly higher percentage of rapidly progressive renal failure patients (RPRF) (39.3 vs 28, p value 0.046). A higher percentage of nephrotics was biopsied in group 2 vs group 1 (46.9 vs 30.4 respectively, p value 0.008). The treatment protocol remained similar in both the groups. Evaluation of the transplant biopsies revealed a nonsignificant higher number of rejections in group 1 (11 out of 18) as compared to group 2 (5 out of 16), p value 0.100. Combined rejection saw a lesser use of rATG in group 1.

Conclusion

COVID pandemic induced restrictive measures could have led to selective high risk patients with RPRF as presumptive diagnosis and higher creatinine values getting biopsied. Higher rejections were noticed in transplant recipients pointing towards the need of establishing a more efficient support system for managing such patients.

     

Interactions between marmatite and bornite during the oxidative dissolution process in abiotic and biotic systems

Marmatite and bornite are commonly associated together in nature, and their interactions in an acidic environment are vital for both (bio)hydrometallurgy and acid mine drainage (AMD) production. In this work, dissolution experiments (marmatite : bornite = 2 : 0, 3 : 1, 1 : 1, 1 : 3 and 0 : 2) accompanied by analytic techniques such as electrochemical methods, Raman spectroscopy and synchrotron radiation-XRD (SR-XRD) were utilized to interpret the interactions between marmatite and bornite in acidic abiotic and biotic systems. The dissolution experiments showed that marmatite can significantly accelerate the oxidative dissolution of bornite, especially in the abiotic system. On the contrary, bornite inhibited the oxidative dissolution of marmatite when the percentage of bornite was high. Electrochemical measurements proved that the galvanic interactions between marmatite and bornite were slight and should not be the main cause for the interactions. Combined with the dissolution experiments, analytic techniques and previous references, it could be speculated that marmatite accelerated bornite dissolution mainly by providing an iron source, which acted as the energy source for microorganisms and oxidants. Bornite affected the dissolution of marmatite mainly by Cu²⁺ ions dissolving from bornite. Bornite inhibited the oxidative dissolution of marmatite mainly because a high Cu²⁺ concentration could significantly hinder marmatite dissolution. In addition, the formation of elemental sulfur or jarosite was also one important cause. Bornite intensified marmatite dissolution when the percentage of bornite or the Cu²⁺ concentration was extremely low and then, a synergic dissolution process occurred.

Interactions between marmatite and bornite during the oxidative dissolution process in abiotic and biotic systems.     

Membrane type 1 matrix metalloproteinase is a crucial promoter of synovial invasion in human rheumatoid arthritis

Objective

A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage, and this process requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen‐degrading matrix metalloproteinases (MMPs), membrane type 1 MMP (MT1‐MMP), in synovial pannus invasiveness.

Methods

The expression and localization of MT1‐MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemical analysis of RA joint specimens. The functional role of MT1‐MMP was analyzed by 3‐dimensional (3‐D) collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinases 1 (TIMP‐1), TIMP‐2, or GM6001. The effect of adenoviral expression of a dominant‐negative MT1‐MMP construct lacking a catalytic domain was also examined.

Results

MT1‐MMP was highly expressed at the pannus–cartilage junction in RA joints. Freshly isolated rheumatoid synovial tissue and isolated RA synovial fibroblasts invaded into a 3‐D collagen matrix in an MT1‐MMP–dependent manner. Invasion was blocked by TIMP‐2 and GM6001 but not by TIMP‐1. Invasion was also inhibited by the overexpression of a dominant‐negative MT1‐MMP, which inhibits collagenolytic activity and proMMP‐2 activation by MT1‐MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1‐MMP–dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix.

Conclusion

MT1‐MMP serves as an essential collagen‐degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1‐MMP–dependent invasion may represent a novel therapeutic strategy for RA.

     

Beyond the snare: technically accessible large en bloc colonic resection in the West: an animal study

Background: Endoscopic submucosal dissection (ESD) and circumferential submucosal incision endoscopic mucosal resection (CSI‐EMR) are techniques for en bloc excision of large sessile colonic lesions. Our aims were to compare the efficacy, safety and learning curve of colonic hybrid knife (HK) ESD versus CSI‐EMR for en bloc excision of 50 mm diameter hemi‐circumferential artificial lesions in a porcine model. Patients and Methods: Two separate 50 mm diameter areas of normal recto‐sigmoid mucosa were marked out in each of ten pigs. One was excised with HK‐ESD using succinylated gelatin (SG) submucosal injection. The other was isolated with CSI with the Insulated Tip Knife 2 followed by SG submucosal injection then EMR with a large snare. Euthanasia and colectomy was performed at 72 h followed by blinded histopathology assessment. Results: En bloc excision rates were: HK‐ESD 100% versus CSI‐EMR 20% (P = 0.008). The mean number of resections per lesion was HK‐ESD 1 versus CSI‐EMR 3 (P = 0.001). The mean dimensions of the largest specimen per technique were HK‐ESD 63 × 54 mm versus CSI‐EMR 49 × 41 mm (P = 0.005). Procedure duration mean was HK‐ESD 54 min versus CSI‐EMR 22 min (P < 0.001). When procedure duration was adjusted for the size of the resected en bloc specimen, a statistically significant and accelerated learning effect was noted for HK‐ESD (r = ?0.83, P = 0.003). There were no perforations and no significant bleeding. Conclusions: HK‐ESD with SG submucosal injection is superior to CSI‐EMR for en bloc excision of 50 mm diameter lesions in a porcine model. The technique is rapidly learnt. This novel approach may lower the barrier to colonic ESD for Western endoscopists.