Alternative Treatment Modality Research Articles

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma: New hopes on the horizon

In this editorial, we comment on the article by Wang et al . This manuscript explores the potential synergistic effects of combining zanubrutinib, a novel oral inhibitor of Bruton’s tyrosine kinase, with high-dose methotrexate (HD-MTX) as a therapeutic intervention for primary central nervous system lymphoma (PCNSL). The study involves a retrospective analysis of 19 PCNSL patients, highlighting clinicopathological characteristics, treatment outcomes, and genomic biomarkers. The results indicate the combination’s good tolerance and strong antitumor activity, with an 84.2% overall response rate. The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL, particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B. Furthermore, the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring. In essence, the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL. The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes. While the findings suggest promise, the study’s limitations should be considered, and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Cutaneous Granulomatous Reaction Secondary to Mesotherapy.

The practice of mesotherapy has gained significant popularity due to its convenience and ability top recisely deliver medications to targeted areas within the skin. However, despite its perceived safety, mesotherapy has been associated with various adverse effects, including granulomatous reactions triggered by certain ingredients present in the injected solutions. This case report highlights a woman in her 50s who developed multiple treatment-resistant cutaneous granulomas following mesotherapy treatment for skin rejuvenation. This case underscores the potential severity of adverse reactions associated with mesotherapy, even with ingredients traditionally considered safe. Furthermore, it emphasizes the challenges in diagnosing and managing such reactions, particularly in the absence of clear causative agents. As mesotherapy continues to gain popularity, clinicians must remain vigilant for the possibility of adverse reactions and consider alternative treatment modalities in cases of persistent or severe adverse events.

SMARCA4-deficient undifferentiated gastric carcinoma: a case series and literature review.

Undifferentiated gastric carcinoma, characterized by anaplastic cells lacking distinct features of cytological or architectural differentiation, poses diagnostic and therapeutic challenges. Recent studies have suggested an association between this carcinoma and deficiencies in the SWI/SNF complex, particularly mutations in subunits such as SMARCA4. We herein report six cases of SMARCA4-deficient undifferentiated gastric carcinoma with molecular findings, highlighting the rarity and diagnostic pitfalls of this malignancy. Predominantly occurring in males over 50years, these cases presented with nonspecific symptoms and were often diagnosed at an advanced stage. Histologically, the tumors exhibited a sheet-like growth pattern, reduced or absent epithelial markers, and loss of BRG-1 expression, with molecular analysis confirming SMARCA4 gene mutations. The response to conventional chemotherapy was poor, underscoring the importance of complete surgical resection and the development of alternative treatment modalities.

Recent advances in molecular mechanisms of skin wound healing and its treatments

The skin, being a multifaceted organ, performs a pivotal function in the complicated wound-healing procedure, which encompasses the triggering of several cellular entities and signaling cascades. Aberrations in the typical healing process of wounds may result in atypical scar development and the establishment of a persistent condition, rendering patients more vulnerable to infections. Chronic burns and wounds have a detrimental effect on the overall quality of life of patients, resulting in higher levels of physical discomfort and socio-economic complexities. The occurrence and frequency of prolonged wounds are on the rise as a result of aging people, hence contributing to escalated expenditures within the healthcare system. The clinical evaluation and treatment of chronic wounds continue to pose challenges despite the advancement of different therapeutic approaches. This is mainly owing to the prolonged treatment duration and intricate processes involved in wound healing. Many conventional methods, such as the administration of growth factors, the use of wound dressings, and the application of skin grafts, are used to ease the process of wound healing across diverse wound types. Nevertheless, these therapeutic approaches may only be practical for some wounds, highlighting the need to advance alternative treatment modalities. Novel wound care technologies, such as nanotherapeutics, stem cell treatment, and 3D bioprinting, aim to improve therapeutic efficacy, prioritize skin regeneration, and minimize adverse effects. This review provides an updated overview of recent advancements in chronic wound healing and therapeutic management using innovative approaches.

Influence of Pathophysiological Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

Comparison between Woven EndoBridge and coiling with and without stent assistance for intracranial bifurcation and wide-neck aneurysms: a comprehensive systematic review and meta-analysis.

The recent introduction of the Woven EndoBridge (WEB) has presented an alternative treatment modality for intracranial bifurcation and wide-neck aneurysms with a growing body of literature evaluating its efficacy. However, no previous systematic review has focused on comparing WEB with previously using endovascular approaches, specifically primary coiling (PC) and stent-assisted coiling (SAC). Herein, the authors present the first systematic review summarizing available literature to reach a consensus regarding the safety and effectiveness of WEB. A systematic review of articles identified through a search of PubMed, Embase, Scopus, and Web of Science was conducted. Studies were included if they compared WEB with PC or SAC from any aspect for intracranial aneurysms. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies-of Interventions tool. Meta-analyses of the outcomes based on stent use and rupture status were performed. A total of 16 studies were included. The three endovascular approaches were comparable in terms of baseline characteristics except for older age and smaller aneurysm neck in the PC group (p < 0.05). Moreover, the follow-up duration was shorter in the WEB group (p < 0.05). Although the WEB group demonstrated lower complete and adequate immediate occlusion rates (p < 0.01), the rates at follow-up evaluations were comparable with SAC and PC (p = 0.61 and p = 0.27, respectively). The WEB group experienced significantly fewer unfavorable neurological outcomes than the SAC group (p = 0.04), while comparable to the PC group (p = 0.36). Retreatment rates were comparable between WEB and coiling (p = 0.92). The WEB group had fewer hemorrhagic and thromboembolic complications (p < 0.01 and p = 0.01, respectively), with similar neurological and procedure-related complications compared with combined PC and SAC groups. Lastly, mortality was comparable among the different endovascular approaches. This study provides evidence on the noninferiority of WEB compared with PC and SAC in terms of angiographic outcomes. Meanwhile, our findings on lower complication rates, cost, and improved operative aspects associated with WEB establish this novel endovascular treatment as a safe and effective alternative for the treatment of bifurcation and wide-neck aneurysms.

Nationwide Incidence and Trends in Central Retinal Arterial Occlusion Management: A 5000-Patient Analysis.

Central retinal artery occlusion (CRAO) is a rare and visually debilitating vascular condition characterized by sudden and severe vision loss. CRAO is a compelling target for intravenous alteplase (tPA) and endovascular mechanical thrombectomy (MT) due to pathophysiological similarities with acute ischemic stroke; however, the utility of these interventions in CRAO remains dubious due to limited sample sizes and potential risks. To assess usage and outcomes of tPA and MT in CRAO, we queried the National Inpatient Sample database using International Classification of Disease, Ninth and Tenth edition for patients with CRAO and acute ischemic stroke between 2010 and 2019. Our cohort of 5009 CRAO patients were younger with higher rates of obesity, hypertension, long-term anticoagulant use, and tobacco use compared to acute ischemic stroke patients. CRAO patients had lower rates of tPA administration (3.41% vs 6.21%) and endovascular MT (0.38% vs 1.31%) but fewer complications, including deep vein thrombosis, pneumonia, urinary tract infection, acute kidney injury, and acute myocardial infarction (all P < 0.01). CRAO patients had lower rates of poor functional outcome (31.74% vs 58.1%) and in-hospital mortality (1.2% vs 5.64%), but higher rates of profound blindness (9.24% vs 0.58%). A multivariate regression showed no relationship between tPA and MT and profound blindness, although the limited sample size of patients receiving interventions may have contributed to this apparent insignificance. Further investigation of larger patient cohorts and alternative treatment modalities could provide valuable insights for revascularization therapies in CRAO to optimize visual restoration and clinical outcomes.

Lasers for the Treatment of Nonmelanoma Skin Cancer: A Systematic Review of the Literature.

Lasers may present an alternative treatment modality for the management of nonmelanoma skin cancer (NMSC). To investigate lasers as a definitive treatment of NMSC. A comprehensive search was performed on MEDLINE, the Cochrane Library, and the National Institutes of Health (www.clinicaltrials.gov). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis was used to finalize a list of relevant literature studies evaluating the role of laser therapy for NMSC. Articles published through May 1, 2023, were included. The authors identified 37 studies investigating nonablative and ablative lasers alone and in combination with other lasers, noninvasive imaging, and additional modalities for the treatment of basal cell carcinomas, 10 focusing on squamous cell carcinoma in situ and 3 focusing on the treatment of both basal and squamous cell carcinomas. Although surgical management continues to be superior to laser therapy for the management of high-risk and cosmetically sensitive tumors, laser therapy may be an acceptable alternative for low-risk lesions on the trunk and extremities. However, further studies are needed to optimize parameters, determine maximal efficacy, and provide long-term follow-up before the adoption of laser therapy for NMSC into daily clinical practice.

Course and treatment of diabetes: from cardiovascular risk to catastrophe. Clinical case

As of today, type 2 diabetes mellitus and its complications impose a significant burden on healthcare systems worldwide. Myocardial infarction stands as a leading cause of death among patients with type 2 diabetes mellitus due to macroangiopathy resulting from glucose metabolism disorders and endothelial damage [5]. Unfortunately, even with timely assistance, patients with myocardial infarction may develop mechanical complications such as cardiac aneurysm, posing serious risks of myocardial wall rupture with a high likelihood of fatality. In most cases, interventricular septal rupture occurs, manifesting in 0,21% of cases of ST-segment elevation myocardial infarction (STEMI) and 0,04% of cases of non-STEMI. Surgical correction of the defect remains the only effective treatment method, albeit associated with a high risk of mortality. Consequently, intra- and post-operative complications in such patients prompt the search for alternative treatment modalities, including transcatheter closure of the defect [6]. Interventricular septal rupture more commonly occurs in older patients, women, those with hypertension, and chronic kidney disease. Typically, the defect arises against the backdrop of the first myocardial infarction in the absence of timely or absent reperfusion therapy. Interventricular septal rupture may develop within 1–14 days after STEMI. However, the incidence usually demonstrates a bimodal peak within the first 24 hours or 3–5 days after the infarction [12]. A clinical case of a patient with combined cardiometabolic pathology, namely, severe type 2 diabetes mellitus and post-infarction interventricular septal defect, is presented. The case underscores the issue of comorbidity in severe patients. Successful treatment of the patient was achieved through collaborative efforts of cardiac surgeons, intensivists, cardiologists and endocrinologists.

Effectiveness of Platelet-rich Plasma in Partial-thickness Rotator Cuff Tears: a meta-analysis.

Partial-thickness rotator cuff tears (PTRCTs) commonly affect overhead athletes, leading to a decline in sports performance. Platelet-rich plasma (PRP) is being explored as an alternative treatment modality for individuals with PTRCTs, to reduce discomfort and enhance functional recovery. We conducted a systematic review study of randomized controlled clinical trials to determine the effectiveness of PRP in treating PTRCTs. To determine the effectiveness of PRP in treating PTRCTs. We conducted a comprehensive literature search for randomized controlled trials (RCTs) that compared the effectiveness of PRP with eccentric exercise and placebo injections as treatments for PTRCTs. We searched databases such as the Cochrane Library, Web of Science, PubMed, and EMBASE. The Visual analog scale (VAS) score, American shoulder and elbow surgeon (ASES) score, and Constant-Murley score (CMS) were utilized as outcome measures. Statistical analysis was performed using RevMan 5.3 software. Our meta-analysis included 12 studies involving 762 patients. At six weeks post-treatment, the PRP group had significantly higher VAS scores compared to the control group, indicating improvement (Standard mean difference (SMD), -2.04 [95% Confidence interval (CI), -4.00 to -0.08], I2 =97%, P-value =0.04). Patients who received PRP showed statistically significant improvements in VAS scores at 3 months and 6 months follow-up (SMD, -1.78 [95% CI, -3.03 to -0.52], I2 =96%, P-value =0.005) (SMD, -2.26 [95% CI, -3.77 to -0.76], I2 =97%, P-value =0.003). A statistically significant difference was also observed in VAS scores at the long-term 1-year follow-up (SMD, -2.27 [95% CI, -4.07 to -0.47]; I2 =98%; P-value =0.031). There were statistically significant differences in ASES scores and CMS scores in the short-term (SMD, 1.21 [95% CI, 0.19 to 2.24], I2 =96%, P-value =0.02) (SMD, 2.01 [95% CI, 0.14 to 3.88], I2 =97%, P-value =0.04). However, in the long-term ASES and CMS scores did not show any statistical significance (SMD, 2.06 [95% CI, -0.54 to 4.65], I2 =99%, P-value=0.12) (SMD, 4.36 [95% CI, -5.48 to 14.21], I2 =99%, P-value=0.39). Our findings suggest that PRP treatment is effective in reducing pain for individuals with PTRCTs, providing benefits in the short term and long term. However, its impact on functional recovery appears somewhat constrained and doesn't endure over time. Additionally, significant heterogeneity exists among studies, encompassing variations in PRP composition and control group treatments. Consequently, we conclude that compelling evidence for symptom improvement in PTRCT patients following PRP treatment remains elusive. Level I.

Rare presentation of pyogenic granuloma: a case report

The pyogenic granuloma (PG) Also called lobular capillary hemangioma, is a prevalent tumorlike growth and vascular hyperplasia of the skin and mucous membranes. The condition arises in reaction to a chronic, recurring tissue injury that stimulates an exuberant or excessive tissue repair response. It can manifest at any age. The most common site is gingiva, extra gingival occurrence of PG is rare, although have been reported. Management of PG Depends on the area, size of lesion and patient preferences. However, the conservative surgical excision usually the curative treatment of PG. Alternative treatment modalities that have been employed include laser therapy, corticosteroid injections, cryosurgery, and sclerotherapy. In the case report has described an extra gingival PG which occurred on the lower lip in a 19-year-old female patient. The clinical and histopathological assessments confirmed the diagnosis of PG.

Advancements in de Quervain Tenosynovitis Management: A Comprehensive Network Meta-Analysis

This study presents a network meta-analysis aimed at evaluating nonsurgical treatment modalities for De Quervain tenosynovitis. The primary objective was to assess the comparative effectiveness of nonsurgical treatment options. The systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Searches were performed in multiple databases, and studies meeting predefined criteria were included. Data extraction, risk of bias assessment, and statistical analysis were carried out to compare treatment modalities. The analysis was categorized into short-term (within six weeks), medium-term (six weeks up to six months), and long-term (one year) follow-up. The analysis included 14 randomized controlled trials encompassing various treatment modalities for De Quervain tenosynovitis. In the short-term, extracorporeal shockwave therapy demonstrated statistically significant improvement in visual analog scale pain scores compared with placebo. Extracorporeal shockwave therapy also ranked highest in the treatment options based on its treatment effects. Corticosteroid injections (CSIs) combined with casting and laser therapy with orthosis showed favorable outcomes. Corticosteroid injection alone, platelet-rich plasma injections alone, acupuncture, and orthosis alone did not significantly differ from placebo in visual analog scale pain score. In the medium-term, extracorporeal shockwave therapy remained the top-ranking option for visual analog scale pain score, followed by CSI with casting. In the long-term (one year), CSI alone and platelet-rich plasma injections demonstrated sustained pain relief. Combining CSI with orthosis also appeared promising when compared with CSI alone. Corticosteroid injection with a short duration of immobilization remains the primary and effective treatment for De Quervain tenosynovitis. Extracorporeal shockwave therapy can be considered a secondary option. Alternative treatment modalities, such as isolated therapeutic injection, should be approached with caution because they did not show substantial benefits over placebo. Therapeutic I.

Transbronchial Microwave Ablation of Peripheral Lung Tumors: The NAVABLATE Study.

Image-guided thermal ablation is a minimally invasive local therapy for lung malignancies. NAVABLATE characterized the safety and performance of transbronchial microwave ablation (MWA) in the lung. The prospective, single-arm, 2-center NAVABLATE study (NCT03569111) evaluated transbronchial MWA in patients with histologically confirmed lung malignancies ≤30mm in maximum diameter who were not candidates for, or who declined, both surgery and stereotactic body radiation therapy. Ablation of 1 nodule was allowed per subject. The nodule was reached with electromagnetic navigation bronchoscopy. Cone-beam computed tomography was used to verify the ablation catheter position and to evaluate the ablation zone postprocedure. The primary end point was composite adverse events related to the transbronchial MWA device through 1-month follow-up. Secondary end points included technical success (nodule reached and ablated according to the study protocol) and technique efficacy (satisfactory ablation based on 1-month follow-up imaging). Thirty subjects (30 nodules; 66.7% primary lung, 33.3% oligometastatic) were enrolled from February 2019 to September 2020. The pre-procedure median nodule size was 12.5mm (range 5 to 27mm). Procedure-day technical success was 100% (30/30), with a mean ablative margin of 9.9±2.7mm. One-month imaging showed 100% (30/30) technique efficacy. The composite adverse event rate related to the transbronchial MWA device through 1-month follow-up was 3.3% (1 subject, mild hemoptysis). No deaths or pneumothoraces occurred. Four subjects (13.3%) experienced grade 3 complications; none had grade 4 or 5. Transbronchial microwave ablation is an alternative treatment modality for malignant lung nodules ≤30mm. There were no deaths or pneumothorax. In all, 13.3% of patients developed grade 3 or above complications.

Application of a Novel 3D-Printed Nasal Plug as a Conservative Treatment for Empty Nose Syndrome.

Empty nose syndrome (ENS) is commonly treated by surgery, albeit with limited success. Herein, we introduce our experience of applying a newly developed "3D-printed nasal plug" as an alternative conservative treatment modality. This retrospective study included 20 patients (14 males, 6 females; mean age 46.5 ± 13.5 years) with ENS who underwent the application of the 3D-printed nasal plug at Asan Medical Center between June 2022 and May 2023. Symptom improvement was assessed by Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) before and after applying the nasal plug. Clinical results, such as duration and frequency of plug use, discomfort, and level of satisfaction, were investigated. The mean follow-up duration was 40.3 ± 24.2 weeks. The average duration of nasal plug usage was 10.8 h per day and 5.3 days a week. The ENS6Q scores improved from 19.6 ± 4.6 to 6.8 ± 5.1 (mean reduction 12.8 ± 5.9) after 30 minutes of wearing. Symptom "nose feelings too open" was improved most by a score of 3.0 ± 1.5 (p < 0.001). Thirteen patients (65.0%) reported that the effectiveness of the plug, initially confirmed at the first wearing, was well maintained during the entire follow-up. Four patients (20.0%) wore the nasal plug uninterruptedly throughout the week, whereas nine patients (45.0%) wore it intermittently as needed. Frequently reported complaints with plug usage were 'displacement of the plug' and 'cosmetic concerns' about the visible hook portion. A 3D-designed nasal plug can be a useful conservative treatment option for ENS patients. 4 Laryngoscope, 2024.

Patient Education and Decision Support for Long-Acting Injectable HIV Antiretroviral Therapy: Protocol for Tool Development and Pilot Testing with Ryan White HIV/AIDS Program Medical Case Management Programs in New York.

Long-acting injectable (LAI) HIV antiretroviral therapy (ART) presents a major opportunity to facilitate and sustain HIV viral suppression, thus improving health and survival among people living with HIV and reducing the risk of onward transmission. However, realizing the public health potential of LAI ART requires reaching patients who face barriers to daily oral ART adherence and thus can clinically benefit from alternative treatment modalities. Ryan White HIV/AIDS Program Part A medical case management (MCM) programs provide an array of services to address barriers to HIV care and treatment among economically and socially marginalized people living with HIV. These programs have demonstrated effectiveness in improving engagement along the continuum of care, but findings of limited program impact on durable viral suppression highlight the need to further innovate and hone strategies to support long-term ART adherence. This study aims to adapt and expand Ryan White MCM service strategies to integrate LAI ART regimen options, with the larger goal of improving health outcomes in the populations that could most benefit from alternatives to daily oral ART regimens. In 3 phases of work involving patient and provider participants, this study uses role-specific focus groups to elicit perceptions of LAI versus daily oral ART; discrete choice experiment (DCE) surveys to quantify preferences for different ART delivery options and related supports; and a nonrandomized trial to assess the implementation and utility of newly developed tools at 6 partnering Ryan White HIV/AIDS Program Part A MCM programs based in urban, suburban, and semirural areas of New York. Findings from the focus groups and DCEs, as well as feedback from advisory board meetings, informed the design and selection of the tools: a patient-facing, 2-page fact sheet, including frequently asked questions and a side-by-side comparison of LAI with daily oral ART; a patient-facing informational video available on YouTube (Google Inc); and a patient-provider decision aid. Implementation outcomes, measured through provider interviews, surveys, and service reporting, will guide further specification of strategies to integrate LAI ART options into MCM program workflows. The study was funded in late April 2021 and received approval from the institutional review board in May 2021 under protocol 20-096. Focus groups were conducted in late 2021 (n=21), DCEs ran from June 2022 to January 2023 (n=378), and tools for piloting were developed by May 2023. The trial (May 2023 through January 2024) has enrolled >200 patients. This study is designed to provide evidence regarding the acceptability, feasibility, appropriateness, and utility of a package of patient-oriented tools for comparing and deciding between LAI ART and daily oral ART options. Study strengths include formative work to guide tool development, a mixed methods approach, and the testing of tools in real-world safety-net service settings. Clinicaltrials.gov NCT05833542; https://clinicaltrials.gov/study/NCT05833542. DERR1-10.2196/56892.

Abstract 6675: Dissecting the relationship between mucin 5AC and the lung/gut microbiome in the pathogenesis of K-ras mutant lung cancer

Abstract Non-small cell lung cancer, including its most common subtype, lung adenocarcinoma (LUAD), is one of the most prevalent and lethal forms of cancer worldwide. This is largely due to patients having progressed to an advanced stage of disease by the time of diagnosis. Thus, better understanding the pathogenesis of early LUAD is paramount for the identification of key targets and development of preventive and therapeutic strategies for clinical management of the disease. KRAS mutations are the most common oncogenic driver alteration in human LUAD. Previously, we have found that KRAS mutant LUAD patients whose tumors harbor high expression of Mucin 5 AC (MUC5AC), a main airway secretory mucin, have significantly lower survival and poor prognosis. Mucins are membrane-bound and secreted hydrophilic proteins essential in clearance of allergens, pathogens, and debris in the lung airway. However, overproduction of mucins, such as MUC5AC, plays roles in the pathogenesis of airway diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer. Given the known effect of mucin polymers on bacterial growth and the immune microenvironment in the context of other airway inflammatory diseases, in this study, our objective is to better understand the MUC5AC-to-microbiome relationship using a lung epithelial specific mouse model of KRAS-mutant LUAD (CC-LR) and test the combinatorial effects of genetic deletion of MUC5AC (CC-LR/Muc5ac−/−) and the pan-microbiome depletion on tumor progression, the lung immune contexture, and microbiome (lung and gut). Thus far, we found that genetic deletion of MUC5AC or pan-microbiome depletion significantly decreases the tumor burden (66% vs 50%, respectively). Additionally, both groups show to have a significantly decreased percentage of tumor-specific Ki67+ cells, a cell proliferation marker, and ERG+ cells, an angiogenesis marker, in comparison to the CC-LR controls. The combination of the lack of MUC5AC with pan-microbiome depletion has also shown to reduce tumor development that needs further investigation. These findings highlight the need to better understand the mechanistic interaction between mucins and the lung/gut microbiome in the context of KRAS-mutant lung cancer which we are currently exploring. It also suggests that their relationship could be a key target for modulation, potentially leading to the development of a minimally invasive alternative preventive and/or treatment modality against KRAS-mutant LUAD. Citation Format: Maria T. Grimaldo, Michael J. Clowers, Avantika Krishna, Katherine E. Larsen, Nastaran Karimi, Yasmina H. Rezai, Arnav Gaitonde, Farbod Khalaj, Haoyue Liu, Florencia McAllister, Seyed Javad Moghaddam. Dissecting the relationship between mucin 5AC and the lung/gut microbiome in the pathogenesis of K-ras mutant lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6675.

Immediate effect of Bhastrika Pranayama on cerebral hemodynamics in patient with depression: A case report

BackgroundDepression is a common mental disorder with increasing prevalence in India, which involves cognitive impairment as well. Pharmacological management of depression has many adverse effects, which provides symptomatic relief to the patients, with little to no improvement in cognitive impairment or cerebral hemodynamics. This necessitates the exploration of complementary and alternative treatment modalities. Yoga, in particular Bhastrika pranyama, has been utilized as a complementary practice for various conditions, but evidence of its impact on depression and cerebral hemodynamics is limited. Case detailsA 66-year-old male, previously diagnosed with depression, was admitted to our inpatient hospital for a holistic approach to his condition, combining yoga and naturopathy as part of his treatment. During his stay, he participated in a ten-minute Bhastrika pranayama intervention, conducted under supervision. To evaluate cerebral hemodynamics, a 16-channel functional near-infrared spectroscopy (fNIRS) device was used and changes in oxygenated hemoglobin (oxyHb), deoxygenated hemoglobin (deoxyHb), and total hemoglobin (Total Hb) was recorded. ResultsFollowing the practice of Bhastrika Pranayama, the results indicated a rise in bilateral oxygenated hemoglobin (OxyHb) levels during and immediately after the practice, particularly in the prefrontal cortex region. Simultaneously, a decrease in deoxygenated hemoglobin (DeoxyHb) was observed during the practice, with a slight subsequent increase after the Bhastrika Pranayama session. ConclusionThese preliminary findings indicate that Bhastrika pranayama may have an immediate positive impact on cerebral hemodynamics in patients with depression. Further research with larger sample sizes and controlled studies is needed to confirm and generalize these observations.

Lanosterol regulates abnormal amyloid accumulation in LECs through the mediation of cholesterol pathway metabolism

Age-related cataract (ARC) is the predominant cause of global blindness, linked to the progressive aging of the lens, oxidative stress, perturbed calcium homeostasis, hydration irregularities, and modifications in crystallin proteins. Currently, surgical intervention remains the sole efficacious remedy, albeit carrying inherent risks of complications that may culminate in irreversible blindness. It is urgent to explore alternative, cost-effective, and uncomplicated treatment modalities for cataracts. Lanosterol has been widely reported to reverse cataracts, but the mechanism of action is not yet clear. In this study, we elucidated the mechanism through which lanosterol operates in the context of cataract reversal. Through the targeted suppression of sterol regulatory element-binding protein 2 (SREBP2) followed by lanosterol treatment, we observed the restoration of lipid metabolism disorders induced by SREBP2 knockdown in lens epithelial cells (LECs). Notably, lanosterol exhibited the ability to effectively counteract amyloid accumulation and cellular apoptosis triggered by lipid metabolism disorders. In summary, our findings suggest that lanosterol, a pivotal intermediate in lipid metabolism, may exert its therapeutic effects on cataracts by influencing lipid metabolism. This study shed light on the treatment and pharmaceutical development targeting Age-related Cataracts (ARC).

EFFECT OF LOW LEVEL LASER OF 650NM ON VIALBILITY OF PREVOTELLA INTERMEDIAWITH AND WITHOUT PHOTOSENSITISERS: AN IN VITRO STUDY

Background: Prevotella intermedia is commonly associated with various forms of periodontal disease. Conventional treatment involves a combination of mechanical therapy and systemic antibiotics administration, which comes with its own set of challenges and disadvantages. An alternative treatment modality is low-level laser therapy with and without photosensitizers. Purpose: This study aimed to evaluate the effectiveness of low-level laser therapy with and without the use of photosensitizers, specifically Methylene blue and Toluidine blue, on the viability of Prevotella intermedia. Methods: The study utilized in vitro experiments to assess the impact of low-level laser therapy alone and in combination with photosensitizers on the viability of Prevotella intermedia. Results: The findings indicate that Methylene blue, when combined with low-level laser therapy, exhibits bactericidal effects similar to or greater than low-level laser therapy alone on Prevotella intermedia. Additionally, the use of Toluidine blue as a photosensitizer in combination with low-level laser therapy also led to a reduction in the viability of Prevotella intermedia, although it was not as effective as Methylene blue. Conclusion: Low-level laser therapy, particularly when combined with Methylene blue as a photosensitizer, shows promise as a potential treatment modality for controlling Prevotella intermedia in periodontal diseases.

The effect of injectable platelet rich fibrin as a nonsurgical treatment of the female stress urinary incontinence.

The complications of surgical treatments of stress urinary incontinence have led to the search for less invasive and safer treatment procedures. We aimed to investigate the efficacy of locally administered injectable platelet-rich fibrin (i-PRF), an autologous material that plays an important role in tissue regeneration, in women with stress urinary incontinence. Thirty-four women were included in this prospective, single-center, and interventional study, suffering from stress urinary incontinence refractory to conservative treatment. Three consecutive i-PRF injections were applied to the mid-urethra localization at anterior vaginal wall with an interval of 1month. ICIQ-SF, UDI-6, IIQ-7 and POPDI-6 questionnaires were used to measure pre‑treatment, 1month and 6months post‑treatment symptom severity and the clinical outcomes were recorded. The mean age of the patients was 51.5 ± 9.8years. ICIQ-SF, UDI-6, IIQ-7 and POPDI-6 questionnaires results revealed significant clinical improvement of stress urinary incontinence severity afer the administration of i-PRF (p < 0.001). The results at 1 and 6months after treatment did not change statistically significantly. This study demonstrated that locally administiration of i-PRF is efective in relieving SUI symptoms with high success rates without any adverse effects reported. i-PRF injection may have the potential to be a novel, minimally invasive, and low-risk procedure, that could be an alternative and simple treatment modality to surgery for female patients with stress urinary incontinence. Additionally, it may create new avenues for research on therapeutic implementation of i-PRF.