Five‐year follow up of patients with gastrointestinal stromal tumor: Recurrence‐free survival by risk group

Aim: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. There is limited published data on GIST from the Indian subcontinent. This 5‐year retrospective analysis of 49 patients treated for GIST reports clinical and pathological features and survival outcome by risk stratification. Methods: We reviewed 49 cases of GIST from January 2004 to December 2008. Imatinib was administered after surgery in patients with either high‐risk, residual or metastatic disease and at onset of recurrence or metastatic disease in patients with intermediate risk. Results: The mean age was 50 years (range, 17–80 years). Patients with localized tumor were classified as low (n = 2), intermediate (n = 4) and high risk (n = 32), based on the primary tumor and mitotic index. At a median follow up of 21 months, 2‐year and 3‐year recurrence or progression‐free survival rates were 61 and 39%, respectively, for all patients. The median recurrence‐free survival rate in the intermediate‐risk and high‐risk groups were 7 and 49 months, respectively. The median progression‐free survival in the residual (n = 4) and metastatic disease group (n = 7) was 10 and 29 months, respectively. Conclusion: This study demonstrates the role of imatinib in adjuvant and therapeutic settings. Responses have been durable and most patients tolerate the drug well at clinically effective doses. In view of high recurrence rates in the intermediate‐risk group in our study, it would be better to keep these patients on strict follow up to detect recurrence at the earliest opportunity.     

Preparation of Copper-Decorated Activated Carbon Derived from Platamus occidentalis Tree Fiber for Antimicrobial Applications

This study focuses on a greener approach to synthesizing activated carbon by carbonizing Platamus occidentalis tree fibers (TFSA) with 98% H₂SO₄ at 100 °C. The resulted TFSA was employed as an effective adsorbent for copper ions in aqueous media, yielding copper decorated TFSA (Cu@TFSA). The successful adsorption of copper onto the TFSA was proven through extensive characterization techniques. Herein, the TEM and XPS showed that copper nanoparticles were formed in situ on the TFSA surface, without the use of additional reducing and stabilizing agents nor thermal treatment. The surface areas of TFSA and Cu@TFSA were 0.0150 m²/g and 0.3109 m²/g, respectively. Applying the Cu@TFSA as an antimicrobial agent against Escherica coli ( E. coli) and Salmonella resulted in the potential mitigation of complex secondary pollutants from water and wastewater. The Cu@TFSA exhibited outstanding antimicrobial activity against E. coli and Salmonella in both synthetic and raw water samples. This demonstrated a complete growth inhibition observed within 120 min of exposure. The bacteria inactivation took place through the destruction of the bacteria cell wall and was confirmed by the AFM analysis technique. Cu@TFSA has the potential to be used in the water and wastewater treatment sector as antimicrobial agents.     

A novel N-hydroxy-N′-aminoguanidine derivative inhibits ribonucleotide reductase activity: Effects in human HL-60 promyelocytic leukemia cells and synergism with arabinofuranosylcytosine (Ara-C)

Ribonucleotide reductase (RR; EC 1.17.4.1) is responsible for the de novo conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential for DNA replication. RR is upregulated in tumor cells and therefore considered to be an excellent target for cancer chemotherapy.ABNM-13 (N-hydroxy-2-(anthracene-2-yl-methylene)-hydrazinecarboximidamide), a novel N-hydroxy-N′-aminoguanidine has been designed to inhibit RR activity using 3D molecular space modeling techniques. In this study, we evaluated its effect on human HL-60 promyelocytic leukemia cells. ABNM-13 proved to be a potent inhibitor of RR which was displayed by significant alterations of deoxyribonucleoside triphosphate (dNTP) pool balance and a highly significant decrease of incorporation of radiolabeled cytidine into DNA of HL-60 cells. Diminished RR activity caused replication stress which was consistent with activation of Chk1 and Chk2, resulting in downregulation/degradation of Cdc25A. In contrast, Cdc25B was upregulated, leading to dephosphorylation and activation of Cdk1. The combined disregulation of Cdc25A and Cdc25B was the most likely cause for ABNM-13 induced S-phase arrest. Finally, we combined ABNM-13 with the first-line antileukemic agent arabinofuranosylcytosine (Ara-C) and found that ABNM-13 synergistically potentiated the antineoplastic effects of Ara-C.Due to these promising results, ABNM-13 deserves further preclinical and in vivo testing.     

In vitro metabolism of etoposide (VP-16-213) by liver microsomes and irreversible binding of reactive intermediates to microsomal proteins

We have studied the metabolism of VP-16-213 (etoposide, VP-16), an antitumor agent, by mouse liver microsomes to reactive intermediates and the subsequent covalent binding to microsomal proteins. This metabolism was shown to involve the O-demethylation of VP-16 and resulted in the formation of a 3',4'-dihydroxy derivative (DHVP-16) which was identified by both HPLC and mass spectrometry. The formation of DHVP-16 was cytochrome P-450-mediated as indicated by its dependence on NADPH, its increased production following treatment of mice with phenobarbital, and its marked inhibition by SKF-525A and piperonyl butoxide. Furthermore, DHVP-16 formation required oxygen. Microsomal incubation of VP-16 resulted in an irreversible binding of the drug to the proteins, which was also shown to be cytochrome P-450 dependent. The covalent binding of the VP-16 metabolite(s) was inhibited by DHVP-16 in a dose-dependent fashion, suggesting that the reactive intermediates that bound to proteins were derived from DHVP-16. Electron spin resonance studies indicated that the same semiquinone radical was formed during enzymatic (oxidation or reduction) metabolism of DHVP-16 and the o-quinone derivative of VP-16 (VP-16-Q). VP-16-Q and its semiquinone radical are suggested to be the bioalkylating species.     

Corneal endothelial protection during manual small-incision cataract surgery: A narrative review

Cataract causes bilateral blindness in 20 million people globally, the vast majority of whom live in developing countries. Manual small-incision cataract surgery (MSICS) has emerged as an efficient and economical alternative to phacoemulsification, giving comparable results in terms of final visual gain. One of the important determinants of postoperative visual gain is the status of the corneal endothelium. Multiple factors such as corneal distortion, irrigation solution turbulence, mechanical trauma by instruments, nuclear fragments, intraocular lens contact, and free oxygen radicals, all have been implicated in causing corneal damage during cataract surgery. MSICS with posterior chamber intraocular lens implantation has been reported to cause an endothelial cell loss of 15.83%, which is comparable with other modes of cataract surgery like extracapsular cataract extraction and phacoemulsification. Thorough preoperative assessment of endothelial status and taking necessary steps for endothelial protection during surgery can decrease the endothelial cell loss and overall burden of pseudophakic bullous keratopathy. In addition to surgical techniques, the type of irrigating solutions, ocular viscoelastic devices, intracameral dyes, and drugs all affect the endothelial cell status. This review presents a summary of available literature on the protection of endothelial cells during different steps of MSICS. This is especially relevant for developing countries where large-scale MSICS cataract surgeries are performed to decrease the cataract blindness burden.     

“There is No Easy Way to Say This…”: Communication Challenges in the COVID-19 Intensive Care Unit

How to cite this article: Venkateswaran V, Soni KD, Trikha A. “There is No Easy Way to Say This…”: Communication Challenges in the COVID-19 Intensive Care Unit. Indian J Crit Care Med 2023;27(1):79–81.     

Introduction of cadmium chloride additive to improve the performance and stability of perovskite solar cells

With the increase in the importance of using green energy sources to meet the world''s energy demands, attempts have been made to push perovskite solar cell technology toward industrialization all around the world. Improving the properties of perovskite materials as the heart of PSCs is one of the methods to fabricate favorable photovoltaic (PV) solar cells based on perovskites. Here, cadmium chloride (CdCl₂) was used as an additive source for the perovskite precursor to improve its PV properties. Results indicated CdCl₂ improves the perovskite growth and tailors its crystalline properties, suggesting boosted charge transport processes in the bulk and interfaces of the perovskite layer with electron–hole transport layers. Overall, by incorporation of 1.0% into the MAPbI₃ layer, a maximum power conversion efficiency of 15.28% was recorded for perovskite-based solar cells, higher than the 12.17% for the control devices. The developed method not only improved the PV performance of devices but also boosted the stability behavior of solar cells due to the passivated domain boundaries and enhanced hydrophobicity in the CdCl₂-based devices.

With the increase in the importance of using green energy sources to meet the world''s energy demands, attempts have been made to push perovskite solar cell technology toward industrialization all around the world.