Sensors (Basel). 2022 Dec 24;23(1):172. doi: 10.3390/s23010172.

ABSTRACT

Future deployment of 5G NR base stations in the 6425-7125 MHz band raises numerous concerns over the long-term impact on the satellite transponders located in geostationary orbit. To study this impact and understand whether 5G NR may cause adverse effect to the spaceborne receivers, the research which estimated the interference levels to the satellite bent pipe links was done. The study presents the evaluation of aggregate interference from 5G NR base stations located inside the victim satellites' footprints using Monte-Carlo analysis and calculation of signal-to-noise degradation and bit error rates of the fixed-satellite service (FSS) bent-pipe transponders for each scenario. The results of the study showed the feasibility of co-existence between 5G NR and satellite systems in the 6425-7125 MHz bands, and that no negative impact on the performance of the satellite links is expected.

PMID:36616767 | PMC:PMC9824803 | DOI:10.3390/s23010172

Nutrients. 2022 Dec 27;15(1):119. doi: 10.3390/nu15010119.

ABSTRACT

Honeybee products arouse interest in society due to their natural origin and range of important biological properties. Propolis (P) and royal jelly (RJ) attract scientists' attention because they exhibit antioxidant, anti-inflammatory, anti-bacterial, anti-tumor, and immunomodulatory abilities. In this study, we tested whether P and RJ could mitigate the adverse effects of cadmium (Cd) exposure, with particular emphasis on the reproductive function in female rats. In this line, one week of pretreatment was established. Six experimental groups were created, including (i) the control group (without any supplementation), (ii) the Cd group (receiving CdCl2 in a dose of 4.5 mg/kg/day), (iii) the P group (50 mg of P/kg/day), (iv) RJ group (200 mg of RJ/kg/day), (v) P + Cd group (rats pretreated with P and then treated with P and Cd simultaneously), (vi) RJ + Cd group (animals pretreated with RJ before receiving CdCl2 simultaneously with RJ). Cd treatment of rats adversely affected a number of measured parameters, including body weight, ovarian structure and ultrastructure, oxidative stress parameters, increased ovarian Cd content and prolonged the estrous cycle. Pretreatment and then cotreatment with P or RJ and Cd alleviated the adverse effects of Cd, transferring the clusters in the PCA analysis chart toward the control group. However, clusters for cotreated groups were still distinctly separated from the control and P, or RJ alone treated groups. Most likely, investigated honeybee products can alter Cd absorption in the gut and/or increase its excretion through the kidneys and/or mitigate oxidative stress by various components. Undoubtedly, pretreatment with P or RJ can effectively prepare the organism to overcome harmful insults. Although the chemical composition of RJ and P is relatively well known, focusing on proportion, duration, and scheme of treatment, as well as the effects of particular components, may provide interesting data in the future. In the era of returning to natural products, both P and RJ seem valuable materials for further consideration as anti-infertility agents.

PMID:36615776 | PMC:PMC9823550 | DOI:10.3390/nu15010119

Molecules. 2023 Jan 3;28(1):427. doi: 10.3390/molecules28010427.

ABSTRACT

Pain is a common clinical symptom among patients. Although various opioid analgesics have been developed, their side effects hinder their application. This study aimed to develop a novel opioid analgesic, HAGD (H-Tyr-D-AIa-GIy-Phe-NH2), with limited side effects. In vivo studies on mouse models as well as in vitro studies on Chinese hamster ovary (CHO) cells expressing human mu, delta, or kappa opioid receptors (CHOhMOP, CHOhDOP, and CHOhKOP, respectively) and human sperm were conducted. Compared with subcutaneous morphine (10 mg/kg), subcutaneous HAGD (10 mg/kg) produced equipotent or even greater antinociception with a prolonged duration by activating mu/delta opioid receptors in preclinical mouse pain models. The analgesic tolerance, rewarding effects (i.e., conditioned place preference and acute hyperlocomotion), and gastrointestinal transit inhibition of HAGD were significantly reduced compared with those of morphine. Both HAGD and morphine exhibited a withdrawal response and had no impacts on motor coordination. In CHOhMOP and CHOhDOP, HAGD showed specific and efficient intracellular Ca2+ stimulation. HAGD had minimal impact on human sperm motility in vitro, whereas 1 × 10-7 and 1 × 10-8 mol/L of morphine significantly declined sperm motility at 3.5 h. Overall, HAGD may serve as a promising antinociceptive compound.

PMID:36615612 | PMC:PMC9824695 | DOI:10.3390/molecules28010427

Molecules. 2023 Jan 1;28(1):346. doi: 10.3390/molecules28010346.

ABSTRACT

The κ-opioid receptor (KOR) has recently emerged as an alternative therapeutic target for the development of pain medications, without deleterious side effects associated with the μ-opioid receptor (MOR). However, modulation of KOR is currently under investigation for the treatment of depression, mood disorders, psychiatric comorbidity, and specific drug addictions. However, KOR agonists also trigger adverse effects including sedation, dysphoria, and hallucinations. In this respect, there is currently much debate on alternative paradigms. Recent effort has been devoted in search of biased ligands capable of selectively activating favorable signaling over signaling associated with unwanted side effects. On the other hand, the use of partial agonists is expected to allow the analgesia to be produced at dosages lower than those required to produce the adverse effects. More empirically, the unwanted central effects can be also avoided by using peripherally restricted agonists. In this review, we discuss the more recent trends in the design of KOR-selective, biased or partial, and finally, peripherally acting agonists. Special emphasis is given on the discussion of the most recent approaches for controlling functional selectivity of KOR-specific ligands.

PMID:36615540 | PMC:PMC9822356 | DOI:10.3390/molecules28010346

Int J Mol Sci. 2023 Jan 3;24(1):852. doi: 10.3390/ijms24010852.

ABSTRACT

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and the association with other autoimmune diseases is well-documented. There are many therapeutic options for the treatment of MS. Most of the available drugs cause drug-induced liver injury (DILI) to variable extents with heterogeneous clinical and biological manifestations, including liver injury with or without signs of hypersensitivity and autoimmunity. The diagnosis of DILI may be particularly difficult because MS is frequently associated with idiopathic autoimmune hepatitis. Recent advances suggest that MS and immune-mediated DILI could be promoted by genetic factors, including HLA genotype. In addition, some of these drugs may promote hepatitis B virus reactivation. This review explores the potential hepatotoxicity of drugs used to treat MS and the criteria to distinguish DILI from idiopathic autoimmune hepatitis associated with MS. The role of susceptible genes both promoting MS and causing the hepatotoxicity of the drug used for MS treatment is also discussed.

PMID:36614299 | PMC:PMC9821303 | DOI:10.3390/ijms24010852

Int J Environ Res Public Health. 2022 Dec 31;20(1):766. doi: 10.3390/ijerph20010766.

ABSTRACT

Inappropriate prescribing (IP) increases the risk of adverse medication reactions and hospitalizations in elderly patients. Therefore, it is crucial to evaluate prescribing patterns among this population. This study was designed to assess the prevalence of potentially inappropriate medication (PIMs) use and potential prescribing omissions (PPOs) among geriatrics with cardiovascular diseases (CVDs). In addition, it determined the predictors for IP in this population. A multi-center study was performed retrospectively on 605 patients' medical records collected randomly from seven governmental hospitals in Kuwait. Three of these hospitals have specialized cardiac centers (tertiary care). Inclusion criteria were age ≥ 65 years, diagnosed with at least one CVD, and attended the outpatient clinic during the last 6 months before data collection. A total of 383 patients (63.3%; 95% CI: 59.3-67.1%) were found using at least one PIM or having PPO or both, based on STOPP/START criteria. Three hundred and ninety-one patients (64.6%; 95% CI: 60.7-68.4%) were prescribed PIMs categorized as C and/or D medicines according to the Euro-FORTA list. Over one-quarter (28.8%; 95% CI: 25.2-32.6%) of the patients had drug-drug interactions class D that require therapy modification and/or X that should be avoided. Patients taking ≥ five medications had significantly higher PIMs based on STOPP and FORTA criteria, drug-drug interactions (p < 0.001), and significantly higher PPOs based on START criteria (p = 0.041). Patients with three or more chronic diseases had significantly higher PIMs based on STOPP and FORTA criteria and PPOs based on START criteria (p-values: 0.028, 0.035, and 0.005, respectively). Significantly higher PIMs based on STOPP criteria and PPOs based on START criteria were found in general hospitals compared to specialized cardiac centers (p= 0.002, p= 0.01, respectively). These findings highlight the need to develop and implement multifaceted interventions to prevent or minimize inappropriate prescribing among the geriatric population with CVDs in Kuwait.

PMID:36613087 | PMC:PMC9819083 | DOI:10.3390/ijerph20010766

Cells. 2022 Dec 23;12(1):57. doi: 10.3390/cells12010057.

ABSTRACT

Despite potent anticancer activity, the clinical utilization of cisplatin is limited due to nephrotoxicity. As Organic Cation Transporter 2 (OCT2) has been shown to be one of the key transporters involved in the uptake of cisplatin into renal proximal tubules, OCT2 inhibitors such as cimetidine have been explored to suppress cisplatin-induced nephrotoxicity. Nonetheless, the impact of OCT2 inhibition or cimetidine on the anti-cancer effects of cisplatin has not been extensively examined. The main objective of the present study was to quantitatively characterize the anticancer effects of cisplatin and cimetidine and determine their nature of interactions in two cancer cell lines, OCT2-negative hepatocellular carcinoma (HCC) cell line, Huh7, and OCT2-positive breast cancer cell line, MDA-MB-468. First, we determined the static concentration-response curves of cisplatin and cimetidine as single agents. Next, with the help of three-dimensional (3D) response surface analyses and a competitive interaction model, we determined their nature of interactions at static concentrations to be modestly synergistic or additive in Huh7 and antagonistic in MDA-MB-468. These results were consistent with the cell-level pharmacodynamic (PD) modeling analysis which leveraged the time-course effects of drugs as single agents and drug combinations. Our developed PD model can be further used to design future preclinical studies to further investigate the cisplatin and cimetidine combinations in different in vitro and in vivo cancer models.

PMID:36611850 | PMC:PMC9818342 | DOI:10.3390/cells12010057

J Clin Med. 2022 Dec 22;12(1):83. doi: 10.3390/jcm12010083.

ABSTRACT

BACKGROUND: Restriction of oral potassium intake is a necessary dietary intervention for managing chronic hyperkalemia. These dietary changes may have negative impacts on nutrition status, particularly in geriatric cohorts with multiple comorbidities. Sodium zirconium cyclosilicate (SZC) is a newly introduced potassium binder intended for patients with hyperkalemia. We aimed to investigate whether the improvements in hyperkalemia with SZC therapy and the liberation of potassium intake restriction may improve nutrition status in a primarily geriatric patient cohort with chronic hyperkalemia.

METHODS: Patients who were maintained on SZC therapy for at least 3 months were retrospectively studied. Following the initiation of SZC and improvement in hyperkalemia, instructions on the restriction of potassium intake were loosened according to the institutional protocol. The change in nutrition status during the 3 month therapeutic period using SZC was investigated by referencing the prognostic nutritional index score (PNI), geriatric nutritional risk index score (GNRI), and controlling nutritional status (CONUT) scores.

RESULTS: A total of 24 patients (median age 78 years, 58% men, median estimated glomerular filtration rate 29.8 mL/min//1.73 m2) were included. Serum potassium level decreased significantly from 5.4 (5.1, 5.9) to 4.4 (4.2, 4.9) mEq/L without any drug-related adverse events, including hypokalemia. Nutrition-related scores, including the PNI score, the GNRI score, and the CONUT score, improved significantly following 3 months of SZC therapy (p < 0.05 for all). Psoas muscle volume and average days for one movement also improved significantly during the therapeutic period (p < 0.05 for both).

CONCLUSIONS: Mid-term SZC therapy and liberation of potassium intake restriction might improve nutrition status in geriatric patients with chronic hyperkalemia.

PMID:36614883 | DOI:10.3390/jcm12010083

J Clin Med. 2022 Dec 20;12(1):21. doi: 10.3390/jcm12010021.

ABSTRACT

BACKGROUND: pemafibrate is a newly-introduced selective peroxisome proliferator-activated receptor-α modulator, which decreases serum triglyceride levels with few drug-related adverse events and may reduce the risk of adverse cardiovascular events in carefully selected patients with hypertriglyceridemia. We aimed to understand which specific cohorts may benefit or not from pemafibrate therapy for adverse cardiovascular event risk reduction.

METHODS: patients with hypertriglyceridemia at baseline received pemafibrate therapy for two years or until October 2022. The factors that were associated with an increased risk of adverse cardiovascular events, defined as heart failure hospitalization, stroke, and acute coronary syndromes, were investigated.

RESULTS: a total of 121 patients (median 62 years, 88 men) remained on pemafibrate therapy for a median of 566 days without any drug-related adverse events. During a 3-month therapeutic period, triglyceride levels improved significantly from 302 (205, 581) mg/dL to 178 (117, 253) mg/dL (p < 0.001). During the overall therapeutic period, there were nine cardiovascular events. Comorbid chronic heart failure, comorbid coronary disease, and a lower pemafibrate dosing were independently associated with the primary endpoint (p < 0.05 for all). Those with multiple risk factors (N = 30) had a significantly higher cumulative incidence of the primary endpoint as compared with others (27% versus 3%, p < 0.001).

CONCLUSION: pemafibrate significantly improves hypertriglyceridemia. A higher dose of pemafibrate should be considered to reduce the risk of adverse cardiovascular events, particularly in patients with chronic heart failure or coronary disease.

PMID:36614823 | DOI:10.3390/jcm12010021

Int J Mol Sci. 2022 Dec 21;24(1):141. doi: 10.3390/ijms24010141.

ABSTRACT

Cisplatin is associated with dose-limiting nephrotoxicity, and the timely detection of acute kidney injury (AKI) can affect morbimortality. Therefore, this study aimed to investigate the tools for monitoring renal function in AKI. This was a retrospective, cohort study. Cisplatin-treated patients with head and neck cancer were included. Nephrotoxicity was assessed using serum creatinine, estimated creatinine clearance, serum electrolytic alterations, and plasma kidney injury molecule-1 (KIM-1). The toxicity severity was classified according to Common Terminology Criteria for Adverse Events (CTCAE), and AKI was classified by Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN). A total of 81 participants were included, of whom only 32 did not have AKI. Almost 90% of participants had a decreased estimated glomerular filtration rate five (D5) days after chemotherapy. The AKI estimate differs between AKIN and RIFLE; more participants were diagnosed by the RIFLE at D5, 19.5% versus 2.4% by AKIN, and fifteen had a discordance between these classifications. All laboratory markers showed significant changes on D5. KIM-1 appeared a possible biomarker when considering CTCAE or AKIN classifications (p < 0.05 on D5), but not when RIFLE classification was used (p = 0.0780). Further studies may seek to understand the profiles of different biomarkers together.

PMID:36613585 | DOI:10.3390/ijms24010141

Food Chem Toxicol. 2023 Feb;172:113598. doi: 10.1016/j.fct.2022.113598. Epub 2023 Jan 3.

ABSTRACT

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of medications that are routinely been used across the world. Their analgesic, anti-inflammatory, and antipyretic effects have all been well-documented. Moreover, they are been deliberated to have a protective role against various critical diseases such as cancer and cardiovascular diseases. However, the data presented by numerous studies in past have signified the adverse effects of NSAIDs due to overdosing on various systems such as cardiovascular, gastrointestinal, hepatic, renal, neural, etc. Despite substantial studies representing the mechanism behind the clinical risk of NSAIDs, there are very few reviews that have collated comprehensive records of various toxicities caused by overdosing on NSAIDs. As a result, we have presented a comprehensive overview of existing information on NSAIDs in this review. In addition to that, we have concentrated on presenting our understanding of various organ-based toxicities caused due to NSAID's prolonged use/overdosage.

PMID:36608735 | DOI:10.1016/j.fct.2022.113598

Phytomedicine. 2023 Jan;109:154535. doi: 10.1016/j.phymed.2022.154535. Epub 2022 Nov 9.

ABSTRACT

BACKGROUND: The therapeutic benefits of Niaoduqing granules (NDQG) in kidney diseases has been comprehensively studied, but its adverse drug reactions remain unexplored.

OBJECTIVE: To evaluate the safety of NDQG in kidney disease treatment.

METHODS: The literature was searched in Embase, Medline via PubMed, Cochrane Library database, Wanfang database, Chinese National Knowledge Infrastructure, SinoMed, and Chinese VIP Database from inception to January 15, 2022, for randomized controlled trials (RCTs) and observational studies. The ClinicalTrials.gov website was searched for ongoing trials. The frequency and characteristics of adverse drug reactions (ADRs) were the primary and secondary outcomes, respectively. Subgroup analysis were conducted to explore the effects of clinical trial types, different kidney diseases, drug combinations and dosage on the safety of NDQG.

RESULTS: This review included 132 trials comprising 115 RCTs and 17 cohort studies. Additionally, 118 studies reported ADR rates with complete data, including 10381 participants. Regarding ADR frequency, no significant difference was observed between NDQG (7.26%) and control (8.39%) groups (RR = 0.890, 95% confidence interval (CI): 0.788-1.007); with no heterogeneity among the studies (I2 = 0.0%, P = 0.958). ADR frequency in patients with chronic kidney disease (65 trials, n = 5823) was significantly lower in the NDQG treatment group than in the control group (RR = 0.810, 95% CI: 0.67-0.969, I2 = 0.0%, P = 0.993); however, for patients with diabetic nephropathy there was no difference between both groups (26 trials, n = 2166, RR = 1.077, 95% CI: 0.802-1.446, I2 = 0.0%, P = 0.611). Similarly, the incidence of ADR in patients on dialysis and patients with pyelonephritis and nephrotic syndrome was the same for both groups, with 95% CI overlapping the line. For different interventions, including NDQG monotherapy or its combination with other commonly used drugs (including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statin drugs, and compound α-keto acid) or dialysis, the incidence of ADR showed no significant difference between the experimental and control arms. The ADR in the NDQG group primarily affected the gastrointestinal system (64.74%), central and peripheral nervous system (9.07%), whole body (5.79%), and skin and appendages (4.53%). The most common clinical manifestations were diarrhea, nausea, and vomiting.

CONCLUSIONS: Our meta-analysis showed that compared with supportive therapy, the incidence of ADR was similar when NDQG was added. However, current evidence is not definitive and more well-designed and conducted RCTs are warranted to definitively establish the reliable evidence.

PROTOCOL REGISTRATION NUMBER: PROSPERO CRD 42018104227.

PMID:36610168 | DOI:10.1016/j.phymed.2022.154535

J Pharm Pharm Sci. 2022;25:377-390. doi: 10.18433/jpps33020.

ABSTRACT

PURPOSE: Vemurafenib received approval for treatment of BRAF V600 variation metastatic melanoma in August 2011. This study analyzed Vemurafenib-related adverse events (AEs) to detect and characterize relevant safety signals using the real-word-data through the Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS: Disproportionality analyses, including the reporting odds ratio (ROR), the healthcare products regulatory agency (MHRA), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms, were applied to quantify the signals of vemurafenib-related AEs.

RESULTS: Out of 8,042,244 reports gathered from the FAERS, 9554 reports of vemurafenib as the 'primary suspected (PS)' AEs were recognized. Vemurafenib-induced AEs occurrence targeted 23 system organ class (SOC). A total of 138 significant disproportionality PTs was simultaneously reserved according to the four algorithms. Unexpected significant AEs such as sarcoidosis and kidney fibrosis might also occur. The median onset time of vemurafenib-related AEs was 26 days (interquartile range [IQR] 8-97 days), and most of the cases occurred within the first one and two months after vemurafenib initiation.

CONCLUSION: Our study detected potential new AEs signals and might provide powerful support for clinical monitoring and risk identification of vemurafenib.

PMID:36608646 | DOI:10.18433/jpps33020

J Pharm Pharm Sci. 2022;25:369-376. doi: 10.18433/jpps33001.

ABSTRACT

PURPOSE: Osteoporosis is an adverse event of prednisolone. This study aimed to assess prednisolone-induced osteoporosis (PIO) profiles and patient backgrounds by analyzing data from the Japanese Adverse Drug Event Report (JADER) database.

METHODS: The current study focused only on orally administered prednisolone. PIO was defined using preferred terms from the Medical Dictionary for Regulatory Activities. Reporting odds ratio (ROR) at 95% confidence interval (CI) and the time-to-onset profile of PIO were used to evaluate adverse events.

RESULTS: The RORs (95% CI) of the female and male subgroups were 4.73 (4.17-5.38) and 2.49 (2.06-3.00), respectively. The analysis of time-to-onset profiles demonstrated that the median values (interquartile range: 25.0-75.0%) of PIO were 136 (74.0-294.0). The prednisolone treatment duration was significantly longer in the PIO patient group than in the non-PIO patient group. The findings suggest that patients with rheumatoid arthritis, systemic lupus erythematosus, and nephrotic syndrome receiving prednisolone have different age-related PIO profiles.

CONCLUSIONS: Our results suggest that longer prednisolone treatment duration and larger cumulative dose might be risk factors of PIO. The potential risk for PIO should not be overlooked, and careful observation is recommended.

PMID:36608641 | DOI:10.18433/jpps33001

BMC Cancer. 2023 Jan 7;23(1):29. doi: 10.1186/s12885-023-10515-z.

ABSTRACT

PURPOSE: Despite the poor prognosis of triple-negative breast cancer (TNBC), it has been demonstrated that neoadjuvant immunotherapy in combination with chemotherapy can improve the pathologic complete response (pCR) rate and/or long-term outcome of TNBC. However, there have been no real-world studies reporting on the effectiveness of neoadjuvant checkpoint inhibitors in early TNBC.

METHODS: Between November 2019 and December 2021, 63 early TNBC patients treated with anti-PD-1 antibodies (pembrolizumab or camrelizumab) or anti-PD-L1 antibody (atezolizumab) in combination with chemotherapy at seven institutions were included. PCR1 defined as ypT0/Tis and ypN0 was the primary endpoint. Secondary endpoints included pCR2 defined as ypT0/Tis, overall response rate (ORR), disease-free survival (DFS), drug-related adverse events (AEs) and biomarkers.

RESULTS: Among the patients in the current study, 34.9% of patients were able to achieve pCR1, and 47.6% of patients had achieved pCR2. The ORR was 82.5%. 33 patients with non-pCR2 tumors were found to have a median DFS of 20.7 months (95% CI 16.3 months-not reached). The DFS of patients with pCR2 and non-pCR2 after neoadjuvant therapy was significantly different (HR = 0.28, 95% CI 0.10-0.79; P = 0.038). The most common AEs were nausea (63.4%), fatigue (42.7%), leucopenia (30.0%) and elevated transaminase (11.7%).

CONCLUSION: It is possible to achieve a meaningful pCR rate and DFS by combining neoadjuvant checkpoint blockade with chemotherapy in patients with high-risk TNBC. Compared to clinical trials, however, there was a slightly lower pCR rate in this multicentered real-world study.

PMID:36611131 | DOI:10.1186/s12885-023-10515-z

J Perianesth Nurs. 2023 Jan 5:S1089-9472(22)00546-9. doi: 10.1016/j.jopan.2022.10.003. Online ahead of print.

ABSTRACT

PURPOSE: Postoperative sore throat (POST) is a frequent postoperative complication. Pre-induction budesonide inhalation is effective in POST prevention. However, it requires inhaler equipment and patient cooperation. Budesonide spraying on the endotracheal (ETT) cuff is simple and can be performed on most patients requiring endotracheal intubation. This study aims to compare the effects of budesonide spray and K-Y gel as an ETT cuff lubricant on the incidence and severity of POST.

DESIGN: Randomized and triple-blinded study.

METHODS: One hundred patients undergoing elective non-cardiac surgery were randomly allocated into the budesonide group (n = 50) and the K-Y gel group (n = 50). In the budesonide group, 200 mcg of budesonide was sprayed on the cuff of the ETT. For the K-Y gel group, the ETT cuff was lubricated with K-Y gel. A visual analog scale was used to assess the severity of POST at 2, 6, and 24 hours after surgery. Other complications of tracheal intubation and adverse effects of budesonide were also recorded.

FINDINGS: Compared to the K-Y gel group, the budesonide group had a significantly lower overall incidence of POST (30% versus 54%, P = .032) and reduced the risk of POST by 24% (relative risk reduction = 24%, 95% CI, 5.23-42.77, P = .012) as well as the incidence of hoarseness (8.6% vs 34%, P = .001) and cough (0% vs 8%, P = 0.041). No incidence of drug-related side effects was reported in both groups.

CONCLUSIONS: Spraying budesonide on the ETT cuff significantly reduces the incidence and severity of POST.

PMID:36610870 | DOI:10.1016/j.jopan.2022.10.003

Am J Med Sci. 2023 Jan 4:S0002-9629(22)00529-8. doi: 10.1016/j.amjms.2022.12.029. Online ahead of print.

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that is associated with functional disability and reduced quality of life. The central pathology of RA is the inflammation of diarthrodial joints, but approximately 40% of patients experience extra-articular manifestations of RA. Extra-articular manifestations are complications of RA that constitute multisystem disorders, associated with genetic and environmental conditions, and increase mortality in RA patients. Observational studies of RA patients have suggested ethnic disparities exist for minority populations; however, less is known about the distribution and prevalence of RA complications and drug-related problems (DRPs). Our objective was to construct a disease profile of RA-related complications in the Hispanic Mexican-American population compared to the non-Hispanic population of El Paso, Texas.

METHODS: A retrospective study was conducted in a Texas Tech University Health Science Center El Paso from 2009 to 2019 to assess the prevalence of RA-related complications in the Hispanic vs non-Hispanic population. The primary parameters were RA diagnosis, serological status, RA-treatment modalities, and history of associated complications. Data were extracted by chart review and correlated to disease-related and treatment-related complications. STATA was used to perform statistical analyses. A p-value of < 0.05 determined statistical significance.

RESULTS: One thousand five hundred five (N=1505) patients, diagnosed with RA, were included in this study. Of the cohort, 82.52% of patients were females, 76.81% were Hispanic, and 64.12% had no smoking history. From the total cohort, seven hundred fifty-six (N=756) patients had documentation of serological markers (Rheumatoid factor (RF) and/or Anti-cyclic citrullinated peptide (Anti-CCP)); 78.44% of patients whose serological status was documented, were positive for RF and/or Anti-CCP. Multivariate regression analysis revealed Hispanics have 15% and 17% less risk of overall RA complications and drug-related side-effects, respectively, compared to non-Hispanics (p-value <0.0001). However, within the entire cohort, those with a family history of RA had a 44% more risk of complications compared to those without family history (p-value <0.0001). Additionally, modifiable risk factors, i.e., active smoking and alcohol use had a higher complication risk, 19% and 21%, respectively (p-value <0.0001). Significantly, all patients seropositive for RF, and/or anti-CCP had a lower prevalence of RA-related and drug-related complications. However, non-Hispanic patients seropositive for RF or anti-CCP had a higher prevalence of specific complications of RA and DRPs compared to Hispanic patients.

CONCLUSION: In our retrospective review, analysis of sociodemographic characteristics reveals that Hispanic patients paradoxically have less risk of disease-related and treatment-related complications compared to non-Hispanic populations in El Paso, Texas. Genetic predisposition, modifiable environment/lifestyle factors had a higher prevalence of RA complications, congruent with established studies. Further analysis reveals that seropositive RA-patients have decreased complication prevalence compared to seronegative cohorts.

PMID:36610489 | DOI:10.1016/j.amjms.2022.12.029

Cell Mol Life Sci. 2023 Jan 7;80(1):31. doi: 10.1007/s00018-022-04662-y.

ABSTRACT

BACKGROUND AND AIMS: Thiopurine-induced acute pancreatitis (TIP) is one of the most common adverse events among inflammatory bowel disease patients treated with azathioprine (AZA), representing a significant clinical burden. Previous studies focused on immune-mediated processes, however, the exact pathomechanism of TIP is essentially unclear.

METHODS: To model TIP in vivo, we triggered cerulein-induced experimental pancreatitis in mice receiving a daily oral dose of 1.5 mg/kg AZA. Also, freshly isolated mouse pancreatic cells were exposed to AZA ex vivo, and acinar cell viability, ductal and acinar Ca2+ signaling, ductal Cl- and HCO3- secretion, as well as cystic fibrosis transmembrane conductance regulator (CFTR) expression were assessed using microscopy techniques. Ras-related C3 botulinum toxin substrate (RAC1) activity was measured with a G-LISA assay. Super-resolution microscopy was used to determine protein colocalization.

RESULTS: We demonstrated that AZA treatment increases tissue damage in the early phase of cerulein-induced pancreatitis in vivo. Also, both per os and ex vivo AZA exposure impaired pancreatic fluid and ductal HCO3- and Cl- secretion, but did not affect acinar cells. Furthermore, ex vivo AZA exposure also inhibited RAC1 activity in ductal cells leading to decreased co-localization of CFTR and the anchor protein ezrin, resulting in impaired plasma membrane localization of CFTR.

CONCLUSIONS: AZA impaired the ductal HCO3- and Cl- secretion through the inhibition of RAC1 activity leading to diminished ezrin-CFTR interaction and disturbed apical plasma membrane expression of CFTR. We report a novel direct toxic effect of AZA on pancreatic ductal cells and suggest that the restoration of ductal function might help to prevent TIP in the future.

PMID:36609875 | DOI:10.1007/s00018-022-04662-y

Am J Ther. 2023 Jan-Feb 01;30(1):e93. doi: 10.1097/MJT.0000000000001595.

NO ABSTRACT

PMID:36608076 | DOI:10.1097/MJT.0000000000001595

PLoS One. 2023 Jan 6;18(1):e0279928. doi: 10.1371/journal.pone.0279928. eCollection 2023.

ABSTRACT

BACKGROUND: Drug-induced nephrotoxicity is a relatively common preventable cause of acute kidney injury (AKI), providing early recognition and management. The pharmacokinetics or pharmacodynamics of drug-drug interactions may lead to additive or synergistic toxicity. The influx of new medications or off-label use of medications in the critical care setting can lead to additional nephrotoxicities, often challenging to predict or detect. This study evaluates the patterns of medication utilization, their combinations, and the related associations with AKI.

METHODS: We utilized correlation-based network analysis (CNA) to investigate the relationship between medications or their combinations with AKI in a large cohort of critically ill patients in a tertiary medical center between 2007 and 2018. Pairwise medication-AKI correlation analysis was performed to evaluate drug synergistic or additive effects. To investigate the inherent nephrotoxicity of medications, we further analyzed medications that were not paired with any other medications within 24 hours before or after their administration time (isolated medication analysis).

RESULTS: Among 147,289 ICU admissions, we identified 244 associations among 1,555 unique medication types. In pairwise analysis, 233 significant correlations were found among 13,150,198 medication pair instances. In isolated medication analysis, ten significant AKI associations were noted. When stratified by eGFR level, substantial differences between eGFR<90 vs. eGFR≥90 patients were observed. This highlights a need to determine eGFR as a risk factor for nephrotoxicity assessment when drug interactions are considered.

CONCLUSIONS: This large-scale cohort study identified an artificial intelligence model to identify patient-agnostic relationships between medication or their pairs with AKI incidence among critically ill patients. It could be used as a continuous quality assurance tool to monitor drug-associated risk nephrotoxicity.

PMID:36607965 | PMC:PMC9821414 | DOI:10.1371/journal.pone.0279928