Computational analysis of 3D printing: Selecting the better among newly released materials.

Resin-based three-dimensional (3D) printing finds extensive application in the field of dentistry. Although studies of cytotoxicity, mechanical and physical properties have been conducted for newly released 3D printing resins such as Crowntec (Saremco), Temporary Crown Resin (Formlabs) and Crown & Bridge (Nextdent), the resistance of these materials to esterases in saliva has not been demonstrated at the molecular level. Therefore, in this study, the binding affinities and stability of these new 3D printing resins to the catalytic sites of esterases were investigated using molecular docking and molecular mechanics with Poisson-Bolzmann and surface area solvation (MM/PBSA) methods after active pocket screening. Toxicity predictions of the materials were also performed using ProTox-II and Toxtree servers. The materials were analyzed for mutagenicity, cytotoxicity, and carcinogenicity, and LD50 values were predicted from their molecular structures. The results indicated that out of the three novel 3D printing materials, Nexdent exhibited reduced binding affinity to esterases, indicating enhanced resistance to enzymatic degradation and possessing a superior toxicity profile.

Prolonged duration of action of suxamethonium in pregnant and postpartum patients: A registry study.

BACKGROUND: Suxamethonium is hydrolysed by butyrylcholinesterase (BChE) and a low BChE activity can result in a prolonged duration of action of suxamethonium. The BChE activity is reduced during pregnancy and postpartum period by up to 33%. However, it can also be reduced by mutations in the BChE gene. In this study, we assessed BChE activity and mutations in the BChE gene in pregnant and postpartum patients with prolonged duration of action of suxamethonium. It was hypothesised that at least 30% of patients with a low BChE activity did not have a mutation in the BChE gene. METHODS: In this registry study we focused on pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium referred to the Danish Cholinesterase Research Unit (DCRU) between March 2007 and January 2023. Primary outcome was the proportion of patients without a mutation among patients with a low BChE activity. Secondary outcomes were the proportion of patients with a low BChE activity and the proportion of patients with a mutation out of the total number of patients. RESULTS: A total of 40 patients were included and among patients with a low BChE activity, 6% (95% CI: 1%-21%) did not have a mutation. Out of the total number of included patients referred to the DCRU, 90% (95% CI: 76%-97%) had a mutation and 94% (95% CI: 80%-99%) had a low BChE activity. CONCLUSION: Among pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium and a low BChE activity, 6% did not have a mutation in the BChE gene. Our findings suggest that during pregnancy and postpartum clinically relevant prolonged duration of action of suxamethonium rarely occurs in genotypically normal patients.

Prognostication and Prediction of Outcomes in Patients with Organophosphorus and Carbamate Poisoning: A Prospective Cohort Study.

Background: Organophosphorus (OP) and carbamate poisoning are significant concerns in developing nations. This study evaluates the effectiveness of the ChE check mobile, a cholinesterase-rapid bedside diagnostic test, in the diagnosis and management of OP and carbamate poisoning. Materials and methods: We conducted this prospective observational study, involving patients with OP and carbamate poisoning over 1 year (June 2016 to June 2017) at a single tertiary care center. Levels of RBC cholinesterase (E-AChE), butyl cholinesterase (BChE), and various other determinants were systematically coded and analyzed. Results: The study population (n = 60) consisted primarily of males (n = 43; 71.7%), with a mean age of 30.6 (SD: 13.7) years. Monocrotophos (n = 10; 20.4%) and carbofuran (n = 4; 8.1%) were the commonest OP and carbamate compounds, respectively. The median initial atropinization dose was 10 (IQR: 0, 61.5) mg, with a median total administered atropine dose of 116 (IQR: 32, 320) mg. A significant negative correlation was found between E-AChE levels and both the initial atropinization dose (ρ: -0.653, p-value < 0.001) and total atropine requirement (ρ: -0.659, p-value < 0.001) during admission. An E-AChE cut-off of 4 units/g hemoglobin provided an area under the curve of 0.73 (sensitivity: 80.0%, specificity: 68.6%, p-value < 0.001) for predicting moderate to severe peradeniya organophosphorus poisoning. Conclusion: The check mobile device can be a valuable tool for prognosticating patients. There was a significant correlation between low E-AChE levels and the atropine requirement and severity. How to cite this article: Jha A, Hazra D, Yadav B, Zachariah A, Alex R. Prognostication and Prediction of Outcomes in Patients with Organophosphorus and Carbamate Poisoning: A Prospective Cohort Study. Indian J Crit Care Med 2024;28(2):141-147.

Pseudocholinesterase deficiency in ophthalmology: a systematic review.

PURPOSE: Unexpected anesthesia-related complications are among the most feared outcomes of ambulatory surgery. One potential culprit is pseudocholinesterase deficiency, which most commonly presents with protracted apnea, necessitating prolonged mechanical ventilation. We report the first case of pseudocholinesterase deficiency in a Bengali person and the first systematic review of pseudocholinesterase deficiency in ophthalmology. This review analyzed the epidemiology, etiologies, presentation, evaluation, and treatment of pseudocholinesterase deficiency. METHODS: Searches were conducted in PubMed, Embase, and Medline through August of 2022 for publications related to pseudocholinesterase deficiency in ophthalmology. In total, 689 studies were screened by two independent reviewers with 26 full-text articles examined for inclusion eligibility. Nineteen studies were eligible and included in the final analysis. RESULTS: Of the 16 identified cases of pseudocholinesterase deficiency, nine (56%) were drug-induced, four (25%) were inherited deficiencies, and in one (6%) of the cases, the cause could not be determined. In two (13%) cases, pseudocholinesterase deficiency could not be confirmed or ruled out. The duration of post-operative apnea ranged from 10 minutes to 14 hours. Continued ventilatory support was the main treatment for all cases and all patients made a full recovery. CONCLUSIONS: Pseudocholinesterase deficiency is a rare, but potentially fatal, anesthetic complication that results in prolonged apnea, respiratory distress, and dependency on ventilators. Ophthalmologists should remain aware of this condition, especially when planning outpatient procedures, as ambulatory centers may have limited resources for managing prolonged post-operative complications.

Prolonged apnea after ECT in organophosphorus poisoning - the need to redefine norms.

BACKGROUND: Poisoning and deaths by organo-phosphorous (OP) compounds are one of the major causes of death in developing and poor countries, and a common admission in the emergency ward and the ICU. OP compounds act by irreversibly binding to pseudocholinesterase enzyme and hence prolong the apnea in patients being given suxamethonium. We present a unusual case of OP poisoning (OPP) in which prolonged apnea ensued in a patient of severe depression following MECT (modified electroconvulsive therapy) in which suxamethonium was used as muscle relaxant, in whom we were cautious of the side-effect of prior organophosphorus poisoning. Since the cases of OPP are very high worldwide, a thorough knowledge of the interaction of the action of the drug and the receptors on which it acts takes pride of place. This article highlights the nuances in the field of psychiatry and anaesthesia in diagnosis and management of prolonged apnea after ECT. CASE PRESENTATION: A 53/F patient consumed OP 38 days prior to MECT. Since existing literature recommend a delay of 4 weeks and a subminimal dose of suxamethonium to prevent prolonged apnea, both these points were taken into consideration. Despite 38 days post exposure to OP, and a dose of succinylcholine of < 0.3 mg/kg, the patient remained apneic for 3 h. Suxamethionum apnea was managed with elective ventilation. After recovery, patient had no residual effect. Subsequently her pseudocholinesterase levels were done which were found to be very low. CONCLUSION: This case is being presented to emphasize that behaviour of post synaptic receptors cannot be relied upon after OP poisoning and pseudocholinesterase levels needs to be mandatorily checked, irrespective of duration post-exposure. In strong suspects dibucaine number and fluoride number also needs to be estimated.

Butyrylcholinesterase-Protein Interactions in Human Serum.

Measuring various biochemical and cellular components in the blood is a routine procedure in clinical practice. Human serum contains hundreds of diverse proteins secreted from all cells and tissues in healthy and diseased states. Moreover, some serum proteins have specific strong interactions with other blood components, but most interactions are probably weak and transient. One of the serum proteins is butyrylcholinesterase (BChE), an enzyme existing mainly as a glycosylated soluble tetramer that plays an important role in the metabolism of many drugs. Our results suggest that BChE interacts with plasma proteins and forms much larger complexes than predicted from the molecular weight of the BChE tetramer. To investigate and isolate such complexes, we developed a two-step strategy to find specific protein-protein interactions by combining native size-exclusion chromatography (SEC) with affinity chromatography with the resin that specifically binds BChE. Second, to confirm protein complexes' specificity, we fractionated blood serum proteins by density gradient ultracentrifugation followed by co-immunoprecipitation with anti-BChE monoclonal antibodies. The proteins coisolated in complexes with BChE were identified by mass spectroscopy. These binding studies revealed that BChE interacts with a number of proteins in the human serum. Some of these interactions seem to be more stable than transient. BChE copurification with ApoA-I and the density of some fractions containing BChE corresponding to high-density lipoprotein cholesterol (HDL) during ultracentrifugation suggest its interactions with HDL. Moreover, we observed lower BChE plasma activity in individuals with severely reduced HDL levels (≤20 mg/dL). The presented two-step methodology for determination of the BChE interactions can facilitate further analysis of such complexes, especially from the brain tissue, where BChE could be involved in the pathogenesis and progression of AD.

The Role of Butyrylcholinesterase and Iron in the Regulation of Cholinergic Network and Cognitive Dysfunction in Alzheimer's Disease Pathogenesis.

Alzheimer's disease (AD), the most common form of dementia in elderly individuals, is marked by progressive neuron loss. Despite more than 100 years of research on AD, there is still no treatment to cure or prevent the disease. High levels of amyloid-ß (Aß) plaques and neurofibrillary tangles (NFTs) in the brain are neuropathological hallmarks of AD. However, based on postmortem analyses, up to 44% of individuals have been shown to have high Aß deposits with no clinical signs, due to having a "cognitive reserve". The biochemical mechanism explaining the prevention of cognitive impairment in the presence of Aß plaques is still unknown. It seems that in addition to protein aggregation, neuroinflammatory changes associated with aging are present in AD brains that are correlated with a higher level of brain iron and oxidative stress. It has been shown that iron accumulates around amyloid plaques in AD mouse models and postmortem brain tissues of AD patients. Iron is required for essential brain functions, including oxidative metabolism, myelination, and neurotransmitter synthesis. However, an imbalance in brain iron homeostasis caused by aging underlies many neurodegenerative diseases. It has been proposed that high iron levels trigger an avalanche of events that push the progress of the disease, accelerating cognitive decline. Patients with increased amyloid plaques and iron are highly likely to develop dementia. Our observations indicate that the butyrylcholinesterase (BChE) level seems to be iron-dependent, and reports show that BChE produced by reactive astrocytes can make cognitive functions worse by accelerating the decay of acetylcholine in aging brains. Why, even when there is a genetic risk, do symptoms of the disease appear after many years? Here, we discuss the relationship between genetic factors, age-dependent iron tissue accumulation, and inflammation, focusing on AD.

Reduced serum cholinesterase activity indicates splenic modulation of the sterile inflammation.

BACKGROUND: Sterile inflammation is an immediate and well-coordinated immune response to surgical injury. The cholinergic system plays a pivotal role in the inflammatory response. Induced inflammation stimulates the vagus nerve, which in turn activates anti-inflammatory nonneuronal processes. Serum cholinesterase (butyrylcholinesterase [BChE]) is an enzyme that hydrolyzes acetylcholine. Measuring the activity of the BChE in blood might indicate the level of the nonneuronal cholinergic activity. The spleen is a major organ of the immune system playing an important role during inflammation. A functional connection of the neuroimmune reflex has thus far been described only in experimental settings. MATERIALS AND METHODS: In 48 patients receiving major pancreatic surgery, BChE activity was measured by applying point-of-care-testing, in addition to standard laboratory tests. RESULTS: The BChE activity decreased in patients receiving surgery. This reduction emerged much earlier than changes in C-reactive protein concentration, an inflammatory biomarker broadly used in the clinical environment. A milder reduction in the BChE activity was observed in patients subjected to surgery with splenectomy than in those with a preserved spleen. CONCLUSIONS: The use of the point-of-care-testing system for quick bedside diagnostics and the rapid effects of inflammation on BChE levels provide a method and a marker to facilitate the early detection of systemic inflammation. Furthermore, this study provides evidence that the experimentally documented neuroimmune interaction is part of the physiological response to surgery-induced sterile inflammation. Splenic function plays an essential role in modulating the cholinergic anti-inflammatory response.

Pseudocholinesterase as a predictor of mortality and morbidity in organophosphorus poisoning.

BACKGROUND: Organophosphorus (OP) pesticide poisoning is a major clinical and public health problem in India. Mortality rate remains high at 15%-30%. AIMS: This prospective, observational study examines the relationship between pseudocholinesterase (PChE) activity and morbidity and mortality in OP poisoning. SETTING AND DESIGN: OP poisoning cases admitted to a tertiary care center Intensive Care Unit (ICU) over 5 years from 2010 to 2014 were studied. METHODS: Patients <16 years of age, those on steroids and those with neuromuscular weakness, were excluded from the study. Serum PChE level at admission was estimated and the severity of poisoning assessed accordingly. Primary outcome measures were ICU length of stay and ventilator-free days. Secondary outcome measures included vasopressor-free days, amount of atropine given, hospital length of stay, and ICU mortality. RESULTS: There were 37 patients included in the study, aged between 24 and 44 years, of which 65% were male. They were divided into two groups according to PChE levels. Group A with PChE levels more than 1000 IU/L had twenty patients and Group B with levels <1000 IU/L had 17 patients. Group B had longer ICU length of stay (P < 0.001) and fewer ventilator-free days (P < 0.001). They also had a fewer vasopressor-free days and a longer stay in hospital. CONCLUSIONS: PChE level at presentation is a reliable indicator of the severity of OP poisoning and a predictor of the need for mechanical ventilation and the duration of stay in the ICU.

A color-reaction-based rapid screening for null activity of butyrylcholinesterase: a step toward point-of-care screening for succinylcholine apnea.

Succinylcholine apnea happens in cases of null butyrylcholinesterase activity after administration of preintubation succinylcholine. So far, there is no such popular test that can rapidly screen null butyrylcholinesterase activity from plasma. Development of a novel method for rapid screening of null butyrylcholinesterase activity of plasma samples was the objective of the current work. Dichromate reagent was added to 1-naphthol, 2-naphthol, phenol, and para-nitrophenol in separate aliquots and watched for the color formation. Plasma samples preincubated with and without selective butyrylcholinesterase inhibitor were mixed with 1-naphthylacetate and watched for color development after addition of dichromate reagent. Fitting of 1-naphthylacetate at the active site of butyrylcholinesterase was analyzed by using tools of computational biology. It was seen that 1-naphthol formed color with dichromate reagent in a concentration-dependent manner. Other phenols did not form color with dichromate reagent even at 500-µm concentrations. Plasma sample with and without selective butyrylcholinesterase inhibitor (tetra isopropyl pyrophosphoramide) was distinguishable by color formation when incubated with 1-naphthylacetate, followed by the addition of dichromate reagent. In silico analysis also showed that 1-naphthylacetate fitted well at the active site of butyrylcholinesterase. The developed method may be used for rapid screening for null butyrylcholinesterase activity at point of care.

Butyrylcholinesterase levels and subjective effects of smoked cocaine in healthy cocaine users.

BACKGROUND: Butyrylcholinesterase (BChE) is beginning to attract attention as a possible target for cocaine abuse treatment because of its role in metabolizing cocaine. OBJECTIVE: The purpose of this analysis was to assess whether endogenous BChE levels are associated with the subjective effects of cocaine. METHODS: Data from 28 participants in five inpatient cocaine self-administration studies were included in the present analysis. Four minutes after each smoked cocaine dose, participants rated their drug-related effects from 0-100 using a computerized self-report Visual Analogue Scale (VAS). The main outcome measures were nine change-in-VAS ratings between a baseline placebo dose and a 25-mg smoked cocaine dose. RESULTS: After controlling for age, sex, total years of cocaine use, total milligrams of cocaine administered before the 25-mg dose being analyzed, and baseline diastolic blood pressure, endogenous BChE was not significantly associated with any of the nine change-in-VAS ratings. CONCLUSION: Though BChE appears to be a possible target for cocaine abuse treatment, these data suggest that endogenous levels of BChE may not play a role in modifying the subjective effects of cocaine. Future larger studies of BChE in respect to the subjective effects produced by cocaine are needed to confirm or refute these findings.

Serum Organophosphorus compound levels as a surrogate marker for severity assessment and management in Acute Organophosphorus Poisoning - A novel approach.

Organophosphorus (OP) compounds are the most extensively used pesticides' class worldwide; cause most self­poisoning deaths especially in India. Thus, it is utmost important for early identification and aggressive management of OP poisoning from the clinical perspective to prevent serious complications by using sophisticated LC-MS/MS approach. This was a prospective study involving 103 patients of OP cases admitted to Karnataka Institute of Medical Sciences from June 2022 to May 2023, based on the inclusion and exclusion criteria patients were subjected to study. On admission, venous blood was collected from patient with Malathion and Profenofos OP poisoning history and subjected to serum biomarker and to LC-MS/MS analysis. Out of the 103 patients, 68 patients consumed Profenofos (66%) and 35 patients consumed Malathion (34%). Pseudocholinesterase levels among the of OP cases revealed that the 33 patients had mild toxicity, 40 patients had moderate toxicity and 30 patients had severe toxicity of OP poisoning. Subsequently LC-MS/MS analysis showed that the results obtained are not in correlation with indirect serum marker pseudocholinesterase levels. On the other side, LC-MS/MS results are in correlation with the clinical outcome of the patients with respect to morbidity and mortality. Thus, LC-MS/MS approach to assess the OP levels in patients could be used as potential diagnostic and prognostic marker for the absolute quantification of OP compounds compared to indirect OP levels estimation.

Early Neurophysiological Monitoring of Train of Four Assists in the Detection of Pseudocholinesterase Deficiency.

A craniotomy with cortical and subcortical mapping was planned for a 64-year-old male with a large right frontotemporal brain mass. Total intravenous anesthesia was performed, and 200 milligrams of succinylcholine was administered at induction. A train of four prior to head pinning (52 minutes after succinylcholine administration) revealed zero of four twitches in the left hand and foot. The patient did not regain spontaneous breathing despite discontinuation of infusions and the surgeon canceled the case at 108 minutes from induction. The patient was safely extubated at 270 minutes. Pseudocholinesterase deficiency was suspected, and labs revealed that the patient was outside of the normal range for pseudocholinesterase enzyme at 698 units/L with a dibucaine inhibition number of 40. The patient's procedure was rescheduled 2 days later, and neuromuscular blockade was avoided. The procedure went ahead as planned with successful mapping and monitoring. This case highlights the effect of pseudocholinesterase deficiency on neuromonitoring and the importance of running train of four early on to detect neuromuscular junction issues in high-risk procedures. In this case, the surgeon was able to avoid pinning and positioning the patient and rescheduled the procedure so that motor mapping, direct cortical motor evoked potentials, and transcranial motor evoked potentials could be successfully performed.

Integrative Approach to Address Male Infertility: A Case Study on Organophosphorus Compound Exposure and Traditional Medicinal Interventions.

Factors, including exposure to substances like organophosphorus compounds (OPCs), have been linked to fertility issues, which are a growing concern. In this case study, a 29-year-old farmer and his 26-year-old wife, married for the past five years, faced challenges conceiving despite several attempts. It was found that the husband's exposure to OPCs like chlorpyrifos, malathion, diazinon, etc., had impacted the quality of his sperm. However, after undergoing treatments and making lifestyle changes such as panchakarma therapy and taking Shilajit supplements, there was an improvement in sperm quality. Through in vitro fertilization using physiological intracytoplasmic sperm injection, successful fertilization and the development of high-quality blastocysts were achieved. This case demonstrates the potential for addressing infertility caused by toxins through a blend of traditional medicinal practices and modern reproductive technologies. It underscores the need for research into strategies that can reduce the effects of OPC exposure on male fertility.

Prognostic significance of estimation of pseudocholinesterase activity and role of pralidoxime therapy in organophosphorous poisoning.

BACKGROUND: Organophosphorous (OP) poisoning is one of the most common poisonings seen in India. OP compounds act through inhibition of enzyme acetylcholinesterase and estimation of pseudocholinesterase (PCE) activity strengthens the diagnosis in clinically uncertain cases of OP poisoning. The role of pralidoxime (PAM) therapy in OP poisoning has been controversial. STUDY OBJECTIVES: This study was aimed to determine the prognostic significance of estimation of PCE activity and also to assess the role of PAM therapy in OP poisoning. MATERIALS AND METHODS: Patients of suspected OP poisoning of age >12 years admitted to emergency unit at a tertiary healthcare center of north India were enrolled. Patients were categorized into two groups; group A who were given intravenous atropine and group B who were given injectable PAM along with atropine. Serum PCE level was estimated at the time of admission in all patients and severity of OP poisoning was assessed according to PCE level. Requirement of atropine, oxygen inhalation, intubation and ventilatory support, total hospital stay, and mortality were compared between different classes of severity and also between Groups A and B. RESULTS: This study included a total of 70 subjects, 35 in each group with mean age of 24.99 ± 8.7 years. Out of 70 subjects 49 (70%) were male and 21 (30%) were female. Forty nine patients (70%) of OP poisoning were with suicidal intent while 21 (30%) cases were accidentally poisoned. In all suicidal cases route of poisoning was ingestion whereas in all the accidental cases route of exposure was inhalational. PCE levels were reduced in all the cases and the mean level was 3,154.16 ± 2,562.40 IU/L. The total dose of atropine required, need for oxygen inhalation and need for intubation and ventilatory support, mean duration of hospital stay and mortality rate (P = 0.003) were higher in moderate to severe cases and did not have significant difference between Groups A and B. CONCLUSION: The study recommends estimation of PCE level at admission to classify severity of OP poisoning and to estimate prognosis. This study did not find any beneficial role of PAM therapy in reducing morbidity as well as mortality.

Butyrylcholinesterase signal sequence self-aggregates and enhances amyloid fibril formation in vitro.

Alzheimer's disease (AD) pathogenesis has been attributed to extracellular aggregates of amyloid ß (Aß) plaques and neurofibrillary tangles in the human brain. It has been reported that butyrylcholinesterase (BChE) also accumulates in the brain Aß plaques in AD. We have previously found that the BChE substitution in 5'UTR caused an in-frame N-terminal extension of 41 amino acids of the BChE signal peptide. The resultant variant with a 69 amino acid signal peptide, designated N-BChE, could play a role in AD development. Here, we report that the signal sequence of the BChE, if produced in an extended 69 aa version, can self-aggregate and could form seeds that enhance amyloid fibril formation in vitro in a dose-dependent manner and create larger co-aggregates. Similar phenomena could have been observed in the human brain if such an extended form of the signal sequence had been, in some circumstances, translated.

Concurrent Change in Serum Cholinesterase Activity and Midregional-Proadrennomedullin Level Could Predict Patient Outcome following Liver Transplantation.

BACKGROUND: After liver transplantation (LTX), patients are susceptible to opportunistic infections resulting in reduced outcomes within the early post-transplantation period. The postoperative monitoring of LTX patients has gained much importance in recent years. However, reliable plasmatic markers predicting 90-day outcomes are still lacking. METHODS: In the post hoc analysis of a prospective, observational study, butyrylcholinesterase (BChE), mid-regional proadrenomedullin (MR-proADM), as well as conventional inflammatory markers (procalcitonin, C-reactive protein) were evaluated in 93 patients at seven consecutive timepoints within the first 28 days following LTX. RESULTS: Persistently reduced activity of BChE and elevated MR-proADM levels indicated reduced 90-day survival following LTX. Furthermore, reduced BChE and increased MR-proADM activity could indicate early post-transplantation bacterial infections, whereas conventional inflammatory biomarkers showed no diagnostic efficacy within the observation period. CONCLUSION: Concurrent assessment of BChE and MR-proADM activity might serve as a bedside diagnostic tool for early bacterial infections following liver transplantation. Thus, a combined utilization of the two biomarkers may be a useful tool in the risk evaluation of patients following liver transplantation.

A Comparative Study of the Triglycerides/HDL Ratio and Pseudocholinesterase Levels in Patients with Bladder Cancer.

BACKGROUND: Lipid alterations may serve as potential tumour biomarkers. The ratio of triglycerides to HDL cholesterol (TG/HDL ratio) is associated with various cancers. Pseudocholinesterase (PChE) activity, involved in TG hydrolysis, plays an important role in the metabolism of lipoprotein. There is scarce data assessing the reliability of both the TG/HDL ratio and PChE levels in correctly classifying patients suffering from bladder cancer. METHODS: Three hundred and ninety-six patients undergoing cystoscopy or transurethral resection of the bladder (TURB), broken into two major groups, i.e., patients with histologically confirmed, non-metastatic bladder cancer (n = 208) and without bladder cancer (no bladder cancer, n = 188), formed the study population. The last group was split into two subgroups consisting of a cohort of patients never suffering from bladder cancer but with other bladder diseases (no CaBD, n = 100) and another cohort formed by patients characterised by eradicated bladder cancer after TURB with no recurrence during a three-month follow-up (previous bladder cancer, n = 88). Pieces of information by both metabolic derangement (the presence of type 2 diabetes mellitus), hypertension and lipid profile were retrieved from patient records upon entry to the study. Sensitivity, specificity, areas under the ROC (AUROC) of the TG/HDL ratio, and PChE levels were used in diagnostic decision making. RESULTS: The TG/HDL ratio as well as PChE concentrations of bladder cancer patients were significantly different when compared to those with previous bladder cancer and the no CaBD patients (p = 0.023 and 0.0004, respectively). There was an independent role of both the TG/HDL ratio and PChE levels in predicting the presence of bladder cancer (OR: 1.22 and 0.99, respectively), but the reliability of the TG/HDL ratio (AUROC: 0.587) was superior to that of PChE levels (AUROC: 0.374). The AUROC of a new parameter resulting from the combination of the TG/HDL ratio with PChE levels showed a further increment in the discriminant power of the bladder cancer presence (0.6298), interestingly with a negative predictive value (89%) according to the Bayesian approach. The cut-off of the TG/HDL ratio, the main marker of the present study that better distinguishes bladder cancer from no bladder cancer patients, was 2.147. DISCUSSION AND CONCLUSIONS: The reliability of the TG/HDL ratio is based on the fact that this parameter likely mirrors the insulin resistance (IR) underlying bladder cancer patients. Furthermore, PChE levels evidence both IR and the associated non-alcoholic fatty liver disease. The TG/HDL ratio and PChE levels as well as their combined use could help physicians to assess/confirm the presence of this very common cancer, where early detection is important to ensure the best therapeutical approach.

Clinical Epidemiology and Predictors of Outcome in Chlorpyrifos Poisoning in Farming and Allied Agricultural Workers in East Godavari, Andhra Pradesh.

Background: Chlorpyrifos is the ninth most consumed pesticide for agricultural purposes in India. It is a chlorinated organophosphate that also causes poisoning in non-target species such as humans. There is a scarcity of published literature on chlorpyrifos intoxication in the Indian scenario. Objective: The objective of the study was to find out the clinical epidemiology and factors influencing the outcome of chlorpyrifos poisoning in the farming and allied agricultural workers. Methodology: The patient record-based cross-sectional study was carried out on 40 confirmed cases of chlorpyrifos poisoning in a tertiary care teaching hospital in East Godavari district, a predominantly agrarian region in the state of Andhra Pradesh. Clinic-demographic profile, aspects of poisoning, outcome in terms of recovery, death, ventilator support were obtained. Mortality or requirement of ventilator support was classified as a bad outcome. Carlsons' Co-morbidity Index, Poison Severity Score, and Glasgow Coma Scale score at the time of admission were assessed objectively. The strength of association between the predictor variables and the outcome was represented using the odds ratio. Statistical analysis was performed using Graph Pad Prism 8.0 trial version. Results: Chlorpyrifos poisoning constituted about 10% of pesticide poisoning and 25% of such cases had a poor outcome. The mean age was 44.73 ± 10.76 years, the majority being farmers. Younger age (<40 years), early reporting to hospital, Carlsons' Co-morbidity Index of less than 8, Glasgow Coma Scale score of more than 12, and Poison severity score of less than 2 were significantly associated with favorable outcome (P < 0.005). During admission, 60% of cases had a plasma pseudocholinesterase level of less than 1000 U/L. Lower plasma pseudocholinesterase was associated with a poor outcome (OR 9.62 CI 4.05-22.84). Conclusions: Farmers and allied agricultural workers are susceptible to chlorpyrifos intoxication. Along with clinical and laboratory parameters, Carlsons' Co-morbidity Index, Glasgow Coma Scale score, and Poison severity score at the time of admission are seen as reliable predictors of outcome.

Assessment of Organophosphate Pesticides Exposure in Men with Idiopathic Abnormal Semen Analysis: A Cross-Sectional Pilot Study.

BACKGROUND: Because of the widespread use of organophosphate (OP) pesticides in agriculture, they are major environmental contaminants in developing countries. OP pesticides decrease sperm concentration and affect its quality, viability, and motility. studies have demonstrated the association between abnormal semen analysis and OP pesticides exposure among the high-risk population. Asthere is limited data on the percentage of OP pesticides exposure, the study aimed to determine the OP pesticides exposure in Southern Indian men with idiopathic abnormal semen analysis and find the possible source of their OP pesticides exposure. MATERIALS AND METHODS: In this cross-sectional pilot study, fifty men with idiopathic abnormal semen analysis as cases and fifty men with normal semen analysis as controls were recruited. Detailed history wastaken and general and systemic examinations were carried out. OP pesticides exposure was determined by assessment of pseudocholinesterase and acetylcholinesterase levels and urinary OP pesticides metabolites dialkyl phosphate (DAP) consisting of dimethyl phosphate (DMP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP). RESULTS: Cases had statistically significantly lower levels of pseudocholinesterase (5792.07 ± 1969.89 vs. 10267.01 ± 3258.58 IU/L) (P=0.006) and acetylcholinesterase [102.90 (45.88-262.74) vs. 570.31 (200.24-975.30) IU/L] (P=0.001) as compared to controls. Cases had a statistically significantly higher percentage of urinary DAP positivity as compared to controls (80 vs. 38%, P<0.0001). Hence, cases had a significantly higher percentage of OP pesticides exposure as compared to controls (20 vs. 4 %, P=0.015). OP-exposed cases had significantly higher urinary DETP and DEDTP levels as compared to OP non-exposed cases. Also, urinary DETP and DEDTP levels were significantly negatively associated with sperm concentration, motility, and normal morphology among OP-exposed cases. CONCLUSION: Southern Indian men with idiopathic abnormal semen analysis had a significantly higher percentage of OP pesticides exposure as compared to men with a normal semen analysis.