Alternative Treatment Research Articles

Implications of Herbal Components in the Treatment of Neurological Disorders

Abstract: Herbal components have been explored as a potential alternative treatment for neurological disorders due to the limitations and potential adverse effects of conventional treatments. Alzheimer’s disease is the most prevalent progressive human neurodegenerative condition marked by senile plaques and neurofibrillary tangles as well as gradual cognitive impairments; the most prominent of which is memory loss. Different therapy techniques incorporating synthetic and herbal approaches are being employed against AD based on the knowledge of the disease process. Commonly used herbal components, such as Ginkgo biloba, Bacopa monnieri, Withania somnifera, Passiflora incarnata, Rhodiola rosea, and Curcuma longa, have been shown to improve symptoms and cognitive function in individuals with neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. However, more research is needed to fully understand the efficacy, safety, and potential interactions with other medications. By continuously exploring and researching the use of herbal components for neurological disorders, we can develop a better understanding of their potential to offer safe and effective alternative treatments.

Targeting Chemoresistance in Advanced Bladder Cancers with a Novel Adjuvant Strategy.

Advanced urinary bladder cancer is characterized by rapid progression and development of therapy resistance. About 30% of the patients are diagnosed with high-grade tumors (grade > T2a). A typical nonsurgical treatment is systemic chemotherapy using cisplatin (C) and gemcitabine (G). However, treatment failure and subsequent disease progression are common in treated patients, and adjuvant therapies are not significantly effective. The therapeutic potential of a molecular hybrid of ursolic acid (UA), a pentacyclic-triterpene conjugated to N-methyl piperazine (UA4), was tested on both naïve (WT) and gemcitabine-resistant (GemR) variants of two human invasive bladder cancer cell lines, 5637 and T24. UA4 killed 5637 (4 µmol/L), T24 (4 µmol/L) WT, and GemR cells in vitro at equal potency. Pretreatment with UA4 followed by G synergistically killed WT and GemR cells by >50% compared with G followed by UA4. Oral gavage of UA4 (100 mg/kg) inhibited WT and GemR tumor growth in athymic mice. UA4 + G was more effective against GemR tumors than either drug alone. Studies revealed cytotoxic autophagy as a mechanism of UA4 cytotoxicity. UA4 induced moderate apoptosis in T24 but not in 5637 cells. Mitochondrial integrity and function were most affected by UA4 because of high levels of reactive oxygen species, disruption of mitochondrial membrane, and cell cycle arrest. These effects were enhanced in the UA4 + G combination. UA4 was well-tolerated in mice, and oral gavage led to a serum level >1 µmol/L with no systemic toxicity. These results show the potential of UA4 as a nontoxic alternative treatment for high-grade bladder cancer.

КАРДИОНЕЙРОАБЛАЦИЯ – ФИЗИОЛОГИЧЕСКИЕ ОСНОВЫ МЕТОДА, КЛИНИЧЕСКОЕ ПРИМЕНЕНИЕ ПРИ НАРУШЕНИЯХ РИТМА СЕРДЦА

Increased tone of the parasympathetic part of the autonomic nervous system, affecting the pacemaker cells, may cause sinus bradycardia, develop long pauses of heart rhythm, paroxysmal or permanent atrioventricular block followed by reflex syncope. The usual reflex syncope treatment is conservative and includes avoiding situations that trigger syncope (prolonged standing, sight of blood etc.), tilt-training, adequate drinking regime, wearing compression underwear, sleeping with the head of the bed elevated and in some cases stimulating neuro- and vegetotropic therapy. Some patients are refractory to conventional methods of treatment and retain severe symptoms that worsens quality of their life seriously. These patients may be required a pacemaker implantation subsequently. Cardioneuroablation is an alternative treatment in patients with overactive parasympathetic nervous system that is based on radiofrequency catheter ablation of the major parasympathetic autonomic ganglia around the heart.

An injectable hydrogel loaded with GMSCs-derived neural lineage cells promotes recovery after stroke.

Ischemic stroke is a devastating medical condition with poor prognosis due to the lack of effective treatment modalities. Transplantation of human neural stem cells or primary neural cells is a promising treatment approach, but this is hindered by limited suitable cell sources and low in vitro expansion capacity. This study aimed i) to use small molecules to reprogram gingival mesenchymal stem cells (GMSCs) commitment to the neural lineage cells in vitro, and ii) to use hyaluronic acid (HA) hydrogel scaffolds seeded with GMSCs-derived neural lineage cells to treat ischemic stroke invivo. Neural induction was carried out with a small molecule cocktail-based one-step culture protocol over a period of 24 hours. The induced cells were analyzed for expression of neural markers with immunocytochemistry and qRT-PCR. The SD rats (n=100) were subjected to the middle cerebral artery occlusion (MCAO) reperfusion ischemic stroke model. Then, after 8 days post-MCAO, the modelled rats were randomly assigned to six study groups (n=12 per group): (i) GMSCs, (ii) GMSCs-derived neural lineage cells, (iii) HA and GMSCs-derived neural lineage cells, (iv) HA, (v) PBS, and (vi) sham transplantation control, and received their respective transplantation. Evaluation of post-stroke recovery were performed by the behavioral tests and histological assessments. The morphologically altered nature of neural lineages has been observed of the GMSCs treated with small molecules compared to the untreated controls. As shown by the qRT-PCR and immunocytochemistry, small molecules further signifcantly enhanced the experession level of neural markers of GMSCs as compared with the untreated controls (all p<0.05). Intracerebral injection of self-assembling HA hydrogel carrying GMSCs-derived neural lineage cells promoted the recovery of neural function and reduced ischemic damage in rats with ischemic stroke, as demonstrated by histological examination and behavioral assessments (all p<0.05). In conclusion, the small molecule cocktail significantly enhanced the differentiation of GMSCs into neural lineage cells. The HA hydrogel was found to facilitate the proliferation and differentiation of GMSCs-derived neural lineage cells. Furthermore, HA hydrogel seeded with GMSCs-derived neural lineage cells could promote tissue repair and functional recovery in rats with ischemic stroke and may be a promising alternative treatment modality for stroke.

Ohwia caudata inhibits doxorubicin-induced cardiotoxicity by regulating mitochondrial dynamics via the IGF-IIR/p-Drp1/PARP signaling pathway.

The most effective drug, doxorubicin (DOX), is widely used worldwide for clinical application as an anticancer drug. DOX-induced cytotoxicity is characterized by mitochondrial dysfunction. There is no alternative treatment against DOX-induced cardiac damage despite intensive research in the present decades. Ohwia caudata has emerged as a potential herbal remedy that prevents from DOX-induced cytotoxicity owing to its pharmacological action of sustaining mitochondrial dynamics by attenuating oxidative stress and inducing cellular longevity. However, its underlying mechanisms are unknown. The novel treatment provided here depends on new evidence from DOX-treated H9c2 cells, which significantly enhanced insulin-like growth factor (IGF) II receptor (IGF-IIR) pathways that activated calcineurin and phosphorylated dynamin-related protein 1 (p-Drp1) at ser616 (p-Drp1[ser616]); cells undergo apoptosis due to these factors, which translocate to mitochondria and disrupt their function and integrity, and in terms of herbal medicine treatment, which significantly blocked these phenomena. Thus, our findings indicate that maintaining integrity of mitochondria is an essential element in lowering DOX-induced cytotoxicity, which further emphasizes that our herbal medicine can successfully block IGF-IIR pathways and could potentially act as an alternative mechanism in terms of cardioprotective against doxorubicin.

A Study on the Effectiveness and Safety of Herbal Extract Combination Compared to 3% Minoxidil Solution for the Treatment of Androgenetic Alopecia: A Randomized, Double-blind, Controlled Trial

Background Androgenetic alopecia (AGA) affects both men and women. Standard treatments include topical minoxidil and oral finasteride, which can cause undesirable side effects. Therefore, a natural herbal extract is required for an alternative treatment. Objectives This study aims to assess both the efficacy and safety profiles of an herbal extract comprising a combination of dihydroquercetin glucoside, epigallocatechin gallate glucoside, zinc, and glycine, compared to the minoxidil solution for the treatment of AGA. Methods About 30 males and 30 females were recruited. The males and females were divided equally into two groups (n=30), randomly receiving either a minoxidil solution or herbal extraction twice a day for 24 weeks. Clinical efficacy, total hair count, and hair mass index (HMI) were evaluated. Results A total of 30 males and 30 females completed the study. The total hair counts (hairs/cm2) at baseline in the herbal group and minoxidil group were 334.8±108.8 and 368.3±178.4, respectively, and the total hair counts at 24 weeks in the herbal group and minoxidil group were 345.0±119.2 and 391.5±183.1 (p&lt;0.001, p&lt;0.001), respectively. The HMI in the herbal and minoxidil groups significantly increased by 25.83±17.18 and 33.70±15.17 (p=0.001, p&lt;0.001) at 24 weeks. However, there was no significant difference in total hair count and HMI between the two groups at 24 weeks (p= 0.250, p=0.065). No local adverse effects were observed in both groups. Conclusions The non-significant difference in efficacy and safety to minoxidil solution suggests that the herbal extraction could be an alternative treatment for AGA. Clinical Trial Registration Number TCTR20220927001.

Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy.

Cerebral adrenoleukodystrophy (CALD) is an X-linked rapidly progressive demyelinating disease leading to death usually within a few years. The standard of care is hematopoietic stem cell transplantation (HSCT), but many men are not eligible due to age, absence of a matched donor, or lesions of the corticospinal tracts (CST). Based on the ADVANCE study showing that leriglitazone decreases the occurrence of CALD, we treated 13 adult CALD patients (19-67 years of age) either not eligible to HSCT (n= 8) or awaiting HSCT (n= 5). Patients were monitored every 3 months with standardized neurological scores, plasma biomarkers and brain MRI comprising lesion volumetrics and diffusion tensor imaging. The disease stabilized clinically and radiologically in 10 patients with up to 2 years of follow-up. Five patients presented with gadolinium enhancing CST lesions that all turned gadolinium negative and, remarkably, regressed in four patients. Plasma neurofilament light chain levels stabilized in all 10 patients and correlated with lesion load. The two patients who continued to deteriorate were over 60 years of age with prominent cognitive impairment. One patient rapidly died from Covid19. These results suggest that leriglitazone can arrest disease progression in adults with early-stage CALD and may be an alternative treatment to HSCT.

Topical moisturizer with rose stem cell-derived exosomes (RSCEs) for recalcitrant seborrheic dermatitis: A case report with 6 months of follow-up.

Seborrheic dermatitis (SD) poses significant treatment challenges due to its chronic nature and the side effects associated with long-term use of conventional therapies like topical corticosteroids. In the search for alternative treatments, exosomes, particularly those derived from rose stem cells (RSCEs), offer a promising avenue due to their potential in managing chronic skin conditions. This case report examines the efficacy of a topical moisturizer containing RSCEs in treating a patient with refractory SD, aiming to provide an alternative treatment pathway. A 40-year-old male with a long-standing history of SD, unresponsive to traditional treatments, underwent a novel treatment regimen. This regimen included an initial topical application of 2.5 mL of RSCEs followed by a maintenance phase involving the application of a RSCE-containing moisturizer. Clinical outcomes were assessed through the Patient's Global Assessment (PGA) and Investigator's Global Assessment (IGA) scores, along with evaluations of scaling and erythema. Remarkable clinical improvement was noted as early as 1-day post-treatment, with significant reductions in redness, scaling, and itching. The patient experienced sustained relief throughout the 6-month follow-up, with a recurrence in the sixth month that was less severe than previous flare-ups. This demonstrated not only the efficacy of RSCEs in symptom management but also their potential in extending remission periods. The chronic management of SD can benefit from innovative treatments like the RSCE-containing moisturizer, as shown in this case report. While the observed outcomes are promising, indicating substantial improvements in skin condition and symptom management, larger controlled studies are necessary to validate the therapeutic potential of exosome-containing moisturizers fully. This case underscores the need for alternative therapies in SD treatment, highlighting the role of exosomes as a viable option.

The Spillover Effects of Extending Liver Transplantation to Patients with Colorectal Liver Metastases: A Discrete Event Simulation Analysis.

Liver transplantation is an alternative treatment for patients with nonresectable colorectal cancer liver-only metastases (CRLM); however, the potential effects on wait-list time and life expectancy to other patients on the transplant waiting list have not been considered. We explored the potential effects of expanding liver transplantation eligibility to include patients with CRLM on wait-list time and life expectancy in Norway. We developed a discrete event simulation model to reflect the Norwegian liver transplantation waiting list process and included 2 groups: 1) patients currently eligible for liver transplantation and 2) CRLM patients. Under 2 alternative CRLM-patient transplant eligibility criteria, we simulated 2 strategies: 1) inclusion of only currently eligible patients (CRLM patients received standard-of-care palliative chemotherapy) and 2) expanding waiting list eligibility to include CRLM patients under 2 eligibility criteria. Model outcomes included median waiting list time, life expectancy, and total life-years. For every additional CRLM patient listed per year, the overall median wait-list time, initially 52 d, increased by 8% to 11%. Adding 2 additional CRLM patients under the most restrictive eligibility criteria increased the CRLM patients' average life expectancy by 10.64 y and decreased the average life expectancy for currently eligible patients by 0.05 y. Under these assumptions, there was a net gain of 149.61 life-years over a 10-y programmatic period, which continued to increase under scenarios of adding 10 CRLM patients to the wait-list. Health gains were lower under less restrictive CRLM eligibility criteria. For example, adding 4 additional CRLM patients under the less restrictive eligibility criteria increased the CRLM patients' average life expectancy by 5.64 y and decreased the average life expectancy for currently eligible patients by 0.12 y. Under these assumptions, there was a net gain of 96.36 life-years over a 10-y programmatic period, which continued to increase up to 7 CRLM patients. Our model-based analysis enabled the consideration of the potential effects of enlisting Norwegian CRLM patients for liver transplantation on wait-list time and life expectancy. Enlisting CRLM patients is expected to increase the total health effects, which supports the implementation of liver transplantation for CRLM patients in Norway. Given the Norwegian donor liver availability, adding patients with nonresectable colorectal cancer liver-only metastases (CRLM) to the liver transplantation waiting list had an overall modest, but varying, impact on total waiting list time.Survival gains for selected CRLM patients treated with liver transplantation would likely outweigh the losses incurred to patients listed currently.To improve the total life-years gained in the population, Norway should consider expanding the treatment options for CRLM patients to include liver transplantation.Other countries may also have an opportunity to gain total life-years by extending the waiting list eligibility criteria; however, country-specific analyses are required.

Characterization of Salmonella phage of the genus Kayfunavirus isolated from sewage infecting clinical strains of Salmonella enterica.

The emergence of multi-drug resistance in Salmonella, causing food-borne infections, is a significant issue. With over 2,600 serovars in in Salmonella sp., it is crucial to identify specific solutions for each serovar. Phage therapy serves as an alternate treatment option. In this study, vB_SalP_792 phage was obtained from sewage, forming plaques in eight out of 13 tested clinical S. enterica isolates. Transmission electron microscopy (TEM) examination revealed a T7-like morphotype. The phage was characterized by its stability, life cycle, antibiofilm, and lytic ability in food sources. The phage remains stable throughout a range of temperatures (-20 to 70°C), pH levels (3-11), and in chloroform and ether. It also exhibited lytic activity within a range of MOIs from 0.0001 to 100. The life cycle revealed that 95% of the phages attached to their host within 3 min, followed by a 5-min latent period, resulting in a 50 PFU/cell burst size. The vB_SalP_792 phage genome has a dsDNA with a length of 37,281 bp and a GC content of 51%. There are 42 coding sequences (CDS), with 24 having putative functions and no resistance or virulence-related genes. The vB_SalP_792 phage significantly reduced the bacterial load in the established biofilms and also in egg whites. Thus, vB_SalP_792 phage can serve as an effective biocontrol agent for preventing Salmonella infections in food, and its potent lytic activity against the clinical isolates of S. enterica, sets out vB_SalP_792 phage as a successful candidate for future in vivo studies and therapeutical application against drug-resistant Salmonella infections.

Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis.

Bariatric intervention has been reported to be an effective way to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in obese individuals. The current systemic review aimed to assess the changes in MRI-determined hepatic proton density fat fraction (MRI-PDFF) and nonalcoholic fatty liver disease activity score (NAS) after bariatric surgery or intragastric balloon/gastric banding in MASLD patients with obesity. We searched various databases including PubMed, OVID Medline, EMBASE, and Cochrane Library. Primary outcomes were the changes in intrahepatic fat on MRI-PDFF and histologic features of metabolic dysfunction-associated steatohepatitis (MASH). Thirty studies with a total of 3,134 patients were selected for meta-analysis. Bariatric intervention significantly reduced BMI (ratio of means, 0.79) and showed 72% of reduction of intrahepatic fat on MRI-PDFF at 6 months after bariatric intervention (ratio of means, 0.28). Eight studies revealed that NAS was reduced 60% at 3-6 months compared to baseline, 40% at 12-24 months, and 50% at 36-60 months. Nineteen studies revealed that the proportion of patients with steatosis decreased by 44% at 3-6 months, 37% at 12-24 months, and 29% at 36-60 months; lobular inflammation by 36% at 12-24 months and 51% at 36-60 months; ballooning degeneration by 38% at 12-24 months; significant fibrosis (≥F2) by 18% at 12-24 months and by 17% at 36-60 months after intervention. Bariatric intervention significantly improved MRI-PDFF and histologic features of MASH in patients with obesity. Bariatric intervention might be the effective alternative treatment option for patients MASLD who do not respond to life style modification or medical treatment.

Acute anterior cruciate ligament rupture: can repair become an alternative to reconstruction: a meta-analysis of randomized controlled trials and cohort studies.

To perform a meta-analysis to compare clinical outcomes of anterior cruciate ligament (ACL) repair and ACL reconstruction for acute ACL rupture. We searched Pubmed, Embase, the Cochrane Library, and Web of Science databases to seek relevant studies. Clinical outcomes included failure rate, hardware removal rate, anteroposterior (AP) knee laxity, and patient-reported outcomes. In addition, subgroup analysis was carried out according to repair techniques, rupture locations, and study designs. Funnel plots were used to detect publication bias. All statistical analysis was performed using STATA (version 14.2, StataCorp). A total of 10 articles were included in this study, comprising 5 randomized controlled trials (RCTs) and 5 cohort studies, involving a total of 549 patients. We found no statistical differences between the ACL repair and ACL reconstruction in the following outcomes: failure rate, AP knee laxity, International Knee Documentation Committee (IKDC) score, Lysholm score, Knee Injury and Osteoarthritis Outcome (KOOS) Score, and Tegner score. However, the ACL repair group had a higher hardware removal rate. Except for AP knee laxity results on different repair techniques, there was no statistical difference in other subgroup analyses. Compared with ACL reconstruction, ACL repair shows similar results in clinical outcomes, and it is promising to be an effective alternative treatment for acute ACL rupture. Larger samples and higher-quality studies are needed to support our results and further explore the advantages of ACL repair in other aspects. Level III.

Prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data.

e15548 Background: FOLFOX and FOLFIRI chemotherapy are considered standard first-line treatment options for colorectal cancer (CRC). However, the criteria for selecting the appropriate treatments have not been thoroughly analyzed. Here, we aim to use machine learning and genetic profiles to identify precise multi-gene panels that can predict the response to 5-Fluorouracil-based chemotherapy in colorectal cancer patients. Methods: The genetic profiling data, including drug response profiles, were retrieved from the Gene Expression Omnibus (GEO) database. These datasets were used to train and validate machine learning models. Feature selection methods, such as least absolute shrinkage and selection operator (LASSO) and variable selection from random forests (varSelRF) and various algorithms, such as Random Forest and Support Vector Machines, were applied to develop predictive models. Functional enrichment and network analyses were performed using Ingenuity Pathway Analysis (IPA). Results: This study identified relevant gene signatures at two stages of colorectal cancer: primary and metastasis using two different chemotherapy regimens, FOLFOX and FOLFIRI. The predictive models achieved an average prediction accuracy of 93% in identifying drug response outcomes across multiple chemotherapy regimens. The application of the machine learning model suggested that 28.6% of patients who failed the treatment therapy they received would benefit from the alternative treatment. Conclusions: The developed machine learning models demonstrate potential for guiding clinicians in selecting the most effective treatment options based on individual genetic profiles. With additional clinical validation, this approach could lead to improvements in treatment outcomes for patients with CRC and other cancers.

Impact of preparation and execution of strategy to mitigate the platinum shortage within a network of community oncology practices.

e13572 Background: The US Oncology Network (USON) is made up of over 600 sites of care and treats 1,400,000 patients annually. Drug shortages have a massive impact on patient outcomes, particularly with limited source oncology medications. Proactive mitigation strategies by the national USON Pharmacy &amp; Therapeutics (P&amp;T) committee are examined to assess impact on cisplatin and carboplatin (cis/carbo) shortages, where a phased approach extended supply for patients. Methods: P&amp;T began implementing gradual reductions in cis/carbo allocations in mid-April 2023. This included stewardship to reserve use in patients with limited alternatives, dose rounding, reducing dose/cycle, and extending cycle interval, when clinically appropriate. As supply depletion became imminent, P&amp;T implemented a novel drug ordering process that restricted cis/carbo use criteria to curative intent without alternative treatment options, requiring case-by-case approval. Comprehensive clinical guidance was developed to provide recommendations for alternative therapies. Alternative regimen templates were built into the centrally managed EHR. To evaluate the impact, drug utilization patterns were tracked during the 6-month shortage (April - September 2023) and compared to historical data. Results: Pronounced impacts were seen during acute supply constraints: cisplatin administrations (admins) and mg decreased to 53% and 48% of baseline, carboplatin admins and mg decreased to 84% and 78%. Compared to the prior 6 months, patients receiving cis/carbo was similar pre-shortage (15,368) vs. during (15,296).Mitigation strategies resulted in preservation of cis/carbo admins for diseases with limited alternatives (NSCLC, head &amp; neck, ovarian/uterine); other cancers with alternatives had a decrease in admins (see table). Dose conservation guidance led to a decrease in average mg administered by 5.1% for cisplatin (72.2 vs. 68.5), and 6.2% for carboplatin (385.5 vs. 361.7). New admins of oxaliplatin increased by 11% (4,230 vs 4,714), primarily in GI malignancies. Conclusions: The rigors of stewardship with a phased approach allowed USON to sustain new patients while conserving cis/carbo for those with limited alternatives. Frequent communication about supply status and conservation guidance was critical for transition to alternative treatment strategies. This experience tested USON organizational readiness for future shortages. [Table: see text]

Inguinal lymphangioma in an adult patient mimicking an irreducible inguinal hernia: A case report

IntroductionLymphangiomas are rare benign vascular malformations of the lymphatic system. They are usually located in the head, neck, and axilla and are typically present during the first two years of life. A few cases of inguinal lymphangioma have been reported in adults. Case presentationWe report a 35-year-old male who presented with left groin swelling for a one-year duration associated with on and off pain. On examination, he had soft, irreducible left inguinal swelling with positive cough impulse and no tenderness on palpation. Ultrasound (US) and magnetic resonance imaging (MRI) were done for him, showing a well-defined lobulated cystic lesion located between subcutaneous and deep fascia measuring around 6.5 × 4.2 × 8.1 cm with multiple internal septations. The lesion shows Low signal intensity in the T1 weighted image and high signal intensity in the T2 weighted image. 97 % alcohol was injected under US guidance and aspirated after 30 min. The swelling significantly decreased in size clinically and radiologically during the follow-up. Clinical discussionLymphangioma rarely occurs in the inguinal region, presenting a diagnostic challenge as it mimics various inguinal conditions. Differential diagnoses include inguinal hernia, hydrocele of the cord, lymphadenopathy, or hematoma. Imaging is used to determine the size, invasion, relation to surrounding structures, and extension to the abdominal cavity. MRI is the diagnostic modality of choice in non-emergency settings. Complete surgical excision is the gold standard for the management with the lowest risk of recurrence. Alternative non-surgical treatment options have been used successfully in poor surgical candidates. Different sclerosing agents have been used with low complications and rates of recurrence. Ethanol is a widely available sclerosing agent, and it was used with no recurrence or side effects during the follow-up period. ConclusionSurgeons should have a high index of suspicion when investigating any inguinal mass, considering such a rare presentation as part of the differential. Sclerotherapy is an effective treatment for lymphangioma and should be considered as an alternative modality in non-surgical candidates.

Blood Purification for the Treatment of Chronic Kidney Disease-associated Pruritus

ABSTRACT Chronic kidney diseases-associated pruritus (CKD-aP) is a term that indicates the itching associated to end stage kidney disease without any apparent cause. This symptom leads to decreased quality of life and increased risk of long-term morbidities and mortality. The pathogenesis of uremic pruritus is still unknown, however, different theories have merged: uremic toxins deposition, immune system dysregulation, peripheral neuropathy, and opioid imbalance. While in the last decade, research focused prevalently on pharmaceutical treatment of CKD-aP, extracorporeal therapies have also evolved providing an alternative but efficient treatment option. In this review, we assess the role of different extracorporeal methods on the treatment of CKD-aP.

Review article: Patients who leave before care is completed: What does the legal duty to warn mean for emergency department clinicians?

Patients leave ED for a variety of reasons and at all stages of care. In Australian law, clinicians and health services owe a duty of care to people presenting to the ED for care, even if they have not yet entered a treatment space. There is also a positive duty to warn patients of material risks associated with their condition, proposed treatment(s), reasonable alternative treatment options and the likely effect of their healthcare decisions, including refusing treatment. This extends to a decision to leave the ED before care is completed. The form of that warning may vary based on what is known about the patient's condition and the associated risks at the time. Specific documentation of warnings given is essential.

Starch nanoparticles with predictable size prepared by alternate treatments of ball milling and ultrasonication

In this study, starch nanoparticles (SNPs) were prepared by alternate treatments of liquid nitrogen ball milling and ultrasonication. The impact, shear and friction forces produced by ball milling, and acoustic cavitation and shear effects generated by ultrasonication disrupted starch granules to prepare SNPs. The SNPs possessed narrow particle size distribution (46.91–210.52 nm) and low polydispersity index (0.28–0.45). Additionally, the SNPs exhibited the irregular fragments with good uniformity. The relative crystallinity decreased from 34.91 % (waxy corn starch, WCS) to 0–25.91 % (SNPs), and the absorbance ratios of R1047/1022 decreased from 0.81 (WCS) to 0.60–0.76 (SNPs). The SNPs had lower thermal stability than that of WCS, characterized by a decrease in Td (temperature at maximum weight loss) from 309.39 °C (WCS) to 300.39–305.75 °C (SNPs). Furthermore, the SNPs exhibited excellent swelling power (3.48–28.02 %) and solubility (0.34–0.97 g/g). Notably, oil absorption capacity of the SNPs (9.77–15.67 g/g) was rather greater than that of WCS (1.33 g/g). Furthermore, the SNPs possessed the lower storage modulus (G′), loss modulus (G″) and viscosity than that of WCS. The SNPs with predictable size and high dispersion capability prepared in this study lay a foundation for expanding the application of SNPs.

AI-driven drug discovery: Exploring Abaucin as a promising treatment against multidrug-resistant Acinetobacter baumannii.

This study presents a comprehensive overview of a well-recognized critical pathogen Acinetobacter baumannii and demonstrates the potential of artificial intelligence (AI) in discovering new antibiotics. It is well-known for causing serious infections, especially in patients admitted to intensive care units, which is further compromised by bacterium's resistance to even last-resort antibiotics like carbapenems, posing critical challenges in its treatment and eradication. This article discusses Abaucin, a revolutionary antibiotic created from artificial intelligence, as a creative and potential treatment for A. baumannii. A comprehensive literature search was conducted using various databases including PubMed, Google Scholar, Cochrane, Science Direct, MEDLINE. Only articles written in English were considered. This correspondence was written after a thorough evaluation of all the articles that discussed Abaucin's discovery, potency against A. baumannii, and the potential of AI in discovering new antibiotics. In addition, references from the selected articles were also examined to ensure a comprehensive review of the literature. This article highlights the discovery of a novel AI-derived antibiotic, Abaucin that offers a promising solution for A. baumannii infections. Abaucin has a narrow range of action that minimizes the risk of inter-pathogen spread of resistance, making the drug more appealing and effective. Its potential to suppress wound infections caused by multidrug-resistant A. baumannii paves a hope for the eradication of superbugs. Further investigation and trials are needed to determine its effectiveness in human subjects and its integrity in the clinical workflow. machine learning (ML) and precision approach could revolutionize treatment strategies. The discovery of Abaucin as an antibiotic to combat drug-resistant A. baumannii bacteria showcases AI and ML's potential to uncover novel antibiotics, thereby offering alternative treatment options. This novel inception of the AI-derived antibiotic, Abaucin marks the first step in introducing an innovative treatment option and represents a substantial leap in the treatment of drug-resistant illnesses and the use of AI in medical advancements.

In vitro assessment of newer colistin-sparing antimicrobial agents for clinical isolates of carbapenem-resistant organisms

ObjectivesCarbapenem-resistant organisms (CROs) are a significant public health threat globally, particularly in countries like India with high antibiotic resistance rates. The current study investigates the prevalence of CROs, detects resistance mechanisms using phenotypic methods and assesses the efficacy of newer antibiotics against CROs. MethodsA prospective study conducted at a tertiary care hospital in India during 2021–23. Clinical specimens were processed and bacterial identification was performed using MALDI-TOF mass spectrometry followed by antimicrobial susceptibility testing using CLSI guidelines against a plethora of newer antibiotics for CROs. Carbapenemase production was detected using phenotypic methods, and the presence of the mcr-1 gene was assessed by real-time PCR. ResultsDuring the study period, predominantly (70 %) Gram-negative bacteria were isolated; amongst which 5692 strains were carbapenem-resistant, wherein resistance to different carbapenems ranged from 34.1% to 79 %. Majority of the carbapenemase producers were metallo-β-lactamases (MBL) producers (75 %). Colistin resistance was noted in 5.4 % of selected carbapenem-resistant isolates. Among newer antibiotics, cefiderocol demonstrated the lowest resistance rates (0–14 %), while resistance to newer β-lactam/β-lactamase inhibitor combinations was very high in carbapenem-resistant isolates. Fosfomycin, minocycline and tigecycline, each showing variable efficacy depending on the site of infection. Moreover, newer β-lactam/β-lactamase inhibitor combinations offer restricted benefits due to widespread prevalence of MBL in the region. ConclusionThe escalating prevalence of CROs in India underscores the urgency for alternative treatment options beyond colistin. Hence, highlighting the critical importance of developing effective strategies to combat carbapenem resistance.