Clinical Dilemma Research Articles

Internally weighted mandibular denture: Addressing severe resorption for enhanced stability and comfort: A case report

The prosthetic rehabilitation resorbed mandibular ridges presents a clinical dilemma when opting not to proceed with endosteal implants. Over time, mandibular complete dentures supplemented with extra weight have demonstrated efficacy in meeting the requirements of patients with significantly resorbed ridges. The weight of such dentures, crafted from cast metal, has conventionally been calculated by taking into account the weight of the wax and the density of the alloy. This clinical report outlines the case of a 68-year-old woman with a significantly resorbed mandibular ridge, emphasizing the application of a weighted mandibular complete denture.

Noma Masquerading as Squamous Cell Carcinoma - A Case Report in an AIDS Patient

Abstract Rationale: Cancrum oris, also known as noma, is a rare and rapidly progressing gangrenous infection affecting the oral cavity, commonly seen in malnourished children. We discuss the clinical presentation, diagnostic dilemma and management in a 54-year-old male human immunodeficiency virus-positive patient with oral ulceration clinically resembling squamous cell carcinoma (SCC). Patient Concerns: The patient had severe oral ulceration with pain and difficulty eating food. Diagnosis: Histopathological examination was misleading as it revealed features akin to early invasion of SCC. Immunohistochemistry findings were not in favour of SCC. Treatment: Antiretroviral therapy was started owing to the decreased CD4 cell count. Outcomes: Lesions began to show signs of healing on follow-up. Take-Away Lessons: This case aims to highlight the unique challenges of diagnosing and emphasises the importance of considering opportunistic infections in immunocompromised patients presenting with oral ulcerations to prevent misdiagnosis and maltreatment.

Deterioration of Performance Status during Palliative Radiotherapy Suggests a Significant Short Survival Duration: Indicating the Necessities for Considering Radiotherapy Discontinuation

Discontinuation of palliative radiotherapy due to a patient’s declining general condition poses a clinical dilemma for palliative care physicians. This study aimed to investigate the survival duration of patients whose performance status (PS) deteriorated during palliative radiotherapy and inform decisions regarding early treatment discontinuation. We retrospectively analyzed data from patients referred from our institute’s palliative care department who underwent ≥10 fractions of palliative radiotherapy between March 2017 and December 2021. PS was assessed using the Eastern Cooperative Oncology Group (ECOG) scale. Survival duration was calculated from the final day of palliative radiotherapy to death using the Kaplan–Meier method. A total of 35 patients underwent palliative radiotherapy. Seven (20%) experienced deterioration in ECOG PS during treatment. Their median survival duration was significantly shorter at 22 days (95% confidence interval: 1–94 days) compared to 125 days (95% confidence interval: 82–150 days) for the 28 patients whose PS remained stable (p = 0.0007). Deterioration in ECOG PS during palliative radiotherapy signifies a markedly shorter survival duration. Careful assessment of a patient’s condition throughout treatment is crucial, and early discontinuation should be considered if their general health worsens rather than strictly adhering to the initial schedule.

3D bioprinted tumor model: a prompt and convenient platform for overcoming immunotherapy resistance by recapitulating the tumor microenvironment.

Cancer immunotherapy is receiving worldwide attention for its induction of an anti-tumor response. However, it has had limited efficacy in some patients who acquired resistance. The dynamic and sophisticated complexity of the tumor microenvironment (TME) is the leading contributor to this clinical dilemma. Through recapitulating the physiological features of the TME, 3D bioprinting is a promising research tool for cancer immunotherapy, which preserves in vivo malignant aggressiveness, heterogeneity, and the cell-cell/matrix interactions. It has been reported that application of 3D bioprinting holds potential to address the challenges of immunotherapy resistance and facilitate personalized medication. In this review, we briefly summarize the contributions of cellular and noncellular components of the TME in the development of immunotherapy resistance, and introduce recent advances in 3D bioprinted tumor models that served as platforms to study the interactions between tumor cells and the TME. By constructing multicellular 3D bioprinted tumor models, cellular and noncellular crosstalk is reproduced between tumor cells, immune cells, fibroblasts, adipocytes, and the extracellular matrix (ECM) within the TME. In the future, by quickly preparing 3D bioprinted tumor models with patient-derived components, information on tumor immunotherapy resistance can be obtained timely for clinical reference. The combined application with tumoroid or other 3D culture technologies will also help to better simulate the complexity and dynamics of tumor microenvironment in vitro. We aim to provide new perspectives for overcoming cancer immunotherapy resistance and inspire multidisciplinary research to improve the clinical application of 3D bioprinting technology.

Abstract 5060: Role of molecular driver mutations in recurrence of early stage laryngeal cancer following narrow field definitive radiotherapy

Abstract PURPOSE/OBJECTIVES Recurrent early-stage laryngeal cancer poses profound clinical and prognostic dilemmas. The primary endpoint of this study was to identify patient exome differences between early-stage laryngeal cancer patients who responded or rapidly progressed following definitive, narrow field radiotherapy. Our study offers the first exploration of mutation patterns in early-stage laryngeal head and neck squamous cell carcinoma (HNSCC) patients receiving curative radiation therapy. MATERIALS/METHODS We identified 36 early-stage laryngeal (T1 = 8, T1a = 4, T1b = 2, T1c = 1, T2 = 20, NA =1) HNSCC patients from the University of Kansas Medical Center treated with definitive narrow field radiotherapy to 63-70 Gray (gy) dose. Whole exome sequencing was performed in all patients. Patients were stratified into “responders” (never failed, N=14) and “non-responders” (recurrence <12 months, N=21). Most non-responder patients with local recurrence underwent total salvage laryngectomy (TSL, N=18). All patients underwent whole exome sequencing. The Genome Analysis Toolkit (GATK) was used for pre-processing and functional annotation of variants. Cancer driver genes were detected for each group using the OncodriveCLUST algorithm. Differentially mutated genes were assessed using Fisher’s exact or exact McNemar’s test at P < 0.05. Tumor mutational burden (TMB) comparisons employed the Wilcoxon rank-sum test with the same threshold. For pathway analysis in Reactome and Ingenuity, a P < 0.1 was used for exploratory significance. RESULTS Mutation analysis identified distinct cancer driver genes between responders, (N=3), non-responders (N=36), and post-TSL (N=4). Among 75 genes with significant pre-treatment mutation differences between responders and non-responders, KCNT2 and AGAP6 were exclusively mutated in non-responders (OR=0, P=0.005 and OR=0, P=0.027, respectively), ADAMTS7 was solely mutated in responders (OR=inf, P=0.019), and PLEC showed more mutations in responders (OR=11.6, P=0.006). Pathway analysis showed these genes were involved in the RND2 GTPase cycle, protein O-glycosylation related diseases, and apoptotic pathways. Post-treatment analysis indicated an enrichment of mutations in apoptosis regulation pathways, with genes like PLEC being more frequently mutated in responders than in non-responders or TSL patients. In addition, we observed in non-responders that they trended towards higher median pre-treatment TMB compared to responders (7.98 vs 6.16, P=0.072). There was no significant difference in TMB between TSL patients and responders or non-responders pre-treatment. CONCLUSION Our analysis reveals distinct mutation patterns in early-stage laryngeal cancer patients by response to radiotherapy and the potential role of these mutated genes in apoptosis related pathways. Citation Format: Aaron Segura, Emily Nissen, Chris Lominska, Ryan Morse, Deri Morgan, Prakash Neupane, Dong Pei, Devin Koestler, Randall Kimple, Umamaheswar Duvvuri, Kevin Sykes, Sufi Thomas, Rohit Nallani, Lisa Shnayder, Kiran Kakarala, Emrullah Yilmaz, Andres Bur. Role of molecular driver mutations in recurrence of early stage laryngeal cancer following narrow field definitive radiotherapy [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 5060.

Identifying antinuclear antibody positive individuals at risk for developing systemic autoimmune disease: development and validation of a real-time risk model.

Positive antinuclear antibodies (ANAs) cause diagnostic dilemmas forclinicians. Currently, no tools exist to help clinicians interpret the significance of a positive ANA in individuals without diagnosed autoimmune diseases. Wedeveloped and validated a risk model to predict risk of developing autoimmune disease in positive ANA individuals. Using a de-identified electronic health record (EHR), we randomly chart reviewed 2,000 positive ANA individuals to determine if a systemic autoimmune disease was diagnosed by a rheumatologist. A priori, we considered demographics, billing codes for autoimmune disease-related symptoms, and laboratory values as variables for the risk model. We performed logistic regression and machine learning models using training and validation samples. We assembled training (n = 1030) and validation (n = 449) sets. Positive ANA individuals who were younger, female, had a higher titer ANA, higher platelet count, disease-specific autoantibodies, and more billing codes related to symptoms of autoimmune diseases were all more likely to develop autoimmune diseases. The most important variables included having a disease-specific autoantibody, number of billing codes for autoimmune disease-related symptoms, and platelet count. In the logistic regression model, AUC was 0.83 (95% CI 0.79-0.86) in the training set and 0.75 (95% CI 0.68-0.81) in the validation set. We developed and validated a risk model that predicts risk for developing systemic autoimmune diseases and can be deployed easily within the EHR. The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals.

Posttonsillectomy Pain Relief and Wound Healing by Applying Bismuth Iodoform Paraffin Paste (BIPP) to Dissected Tonsillar Beds

Abstract Introduction Tonsillectomy is one of the most common operations performed by otorhinolaryngology surgeons worldwide; however, the insufficient quality of the postoperative pain management and effective posttonsillectomy pain relief remain a clinical dilemma. Objective To evaluate the efficacy of applying bismuth iodine paraffin paste (BIPP) to the dissected fossa as an adjuvant therapy for a better outcome in terms of posttonsillectomy pain management and due to its wound healing properties. Methods The present is a prospective randomized control pilot study with 44 patients aged > 7 years who underwent tonsillectomy. The patients were divided into two groups: the control group and the group that had BIPP applied to the dissected tonsillar fossa. The visual analogue scale score and the post-onsillectomy percentage of tonsillar fossa epithelization were recorded and evaluated. Results Both subjectively and objectively, there a was statistically significant pain-relieving effect in the BIPP group within the first 5 postoperative days (p < 0.05). From postoperative day 3 onward, the dissected area of the tonsillar fossa healed significantly faster in the BIPP group compared with the control group, and it became stable on day 14. Conclusion The topical application of BIPP showed a better pain-relieving effect, it was safe, and hastened wound healing after tonsillectomy.

Assessment of treatment outcomes: cytoreductive surgery compared to radiotherapy in oligometastatic prostate cancer - an in-depth quantitative evaluation and retrospective cohort analysis.

The management of oligometastatic prostate cancer, defined by its few metastatic sites, poses distinct clinical dilemmas. Debates persist regarding the most effective treatment approach, with both cytoreductive surgery and radiotherapy being key contenders. The purpose of this research is to thoroughly evaluate and compare the effectiveness of these two treatments in managing patients with oligometastatic prostate cancer. A comprehensive search of the literature was carried out to find pertinent publications that compared the results of radiation and cytoreductive surgery for oligometastatic prostate cancer.A meta-analysis was conducted in order to evaluate both the short- and long-term survival.Furthermore, utilizing institutional patient data, a retrospective cohort research was conducted to offer practical insights into the relative performances of the two treatment regimens. Five relevant studies' worth of data were included for this meta-analysis, which included 1425 patients with oligometastatic prostate cancer.The outcomes showed that, in comparison to radiation, cytoreductive surgery was linked to a substantially better Cancer Specific Survival (CSS) (hazard ratio [HR]: 0.70, 95% [CI]: 0.59-0.81, P<0.001) and Overall Survival (OS)(HR, 0.80; 95% [CI], 0.77-0.82; P < 0.01).The two therapy groups' Progression Free Survival (PFS) and Castration Resistant Prostate Cancer Free Survival(CRPCFS), however, did not differ significantly (HR: 0.56, 95% CI: 0.17-1.06; HR: 0.67, 95% CI: 0.26-1.02, respectively). Out of the 102 patients who were recruited in the retrospective cohort research, 36 had Cytoreductive Surgery(CRP), 36 had radiation therapy (primary lesion), and 30 had radiation therapy (metastatic lesion). The follow-up time was 46.3 months (18.6-60.0) on average. The enhanced OS in the CRP group (OS Interquartile Range (IQR): 45-60 months) in comparison to the radiation group (OS IQR: 39.0-59.0 months and 25.8-55.0 months respectively) was further supported by the cohort research. Furthermore, CRP had a better OS than both radiation (primary region) and radiotherapy (metastatic region), with the latter two therapeutic methods having similar OS. This meta-analysis and retrospective research provide valuable insights into the comparative efficacy of cytoreductive surgery and radiotherapy for oligometastatic prostate cancer. While short term survival(PFS,CRPCFS) were similar between the two groups, cytoreductive surgery exhibited superior CSS and OS.Adverse event rates were manageable in both modalities.These findings contribute to informed treatment decision-making for clinicians managing oligometastatic prostate cancer patients. Further prospective studies and randomized controlled trials are essential to corroborate these results and guide personalized therapeutic approaches for this distinct subset of patients.

In-house molecular diagnosis of diffuse glioma updating the revised WHO classification by a platform of the advanced medical care system, Senshin-Iryo.

Since the World Health Organization (WHO) 2016 revision, the number of molecular markers required for diffuse gliomas has increased, placing a burden on clinical practice. We have established an in-house, molecular diagnostic platform using Senshin-Iryo, a feature of Japan's unique healthcare system, and partially modified the analysis method in accordance with the WHO 2021 revision. Herein, we review over a total 5 years of achievements using this platform. Analyses of IDH, BRAF, and H3 point mutations, loss of heterozygosity (LOH) on 1p/19q and chromosomes 10 and 17, and MGMT methylation were combined into a set that was submitted to Senshin-Iryo as "Drug resistance gene testing for anticancer chemotherapy" and was approved in August 2018. Subsequently, in October 2021, Sanger sequencing for the TERT promoter mutation was added to the set, and LOH analysis was replaced with multiplex ligation-dependent probe amplification (MLPA) to analyze 1p/19q codeletion and newly required genetic markers, such as EGFR, PTEN, and CDKN2A from WHO 2021. Among the over 200 cases included, 54 were analyzed after the WHO 2021 revision. The laboratory has maintained a diagnostic platform where molecular diagnoses are confirmed within 2 weeks. Initial expenditures exceeded the income from patient copayments; however, it has gradually been reduced to running costs alone and is approaching profitability. After the WHO 2021 revision, diagnoses were confirmed using molecular markers obtained from Senshin-Iryo in 38 of 54 cases (70.1%). Among the remaining 16 patients, only four (7.4%) were diagnosed with diffuse glioma, not elsewhere classified, which was excluded in 12 cases where glioblastoma was confirmed by histopathological diagnosis. Our Senshin-Iryo trial functioned as a salvage system to overcome the transition period between continued revisions of WHO classification that has caused a clinical dilemma in the Japanese healthcare system.

Clinical Crossroads: Countertransference, Ethics, and Premature Termination

The literature extensively examines the clinical constructs of countertransference and premature termination through several theoretical orientations. It explores how countertransference is one of the most significant variables in successful therapy outcomes, and how premature termination is often an outcome of a poor therapeutic alliance stemming from the client’s insecure attachment to primary caregivers (Berg & Lundh, 2022; Westerling et al., 2019). However, few studies explore the interconnection of these two constructs and how clinicians process their countertransference when it interferes with their ability to provide effective treatment. Despite the gap in the literature, clinicians are bound to experience countertransference in their work with clients; thus, the literature must provide language to describe these experiences to lessen the feelings of guilt, shame, and uncertainty that tend to emerge through these processes. This clinical note aims to provide a review of these constructs through a case study to emphasize the clinical, ethical, and legal dilemmas clinicians encounter when they experience countertransference throughout the course of therapy. While experiences of countertransference are intimate and painful for the clinician, they are bound to happen; and it is the responsibility of the clinician to address them in the best interest of the client.

Surgical risk stratification in patients with cirrhosis.

Individuals with cirrhosis experience higher morbidity and mortality rates than the general population, irrespective of the type or scope of surgery. This increased risk is attributed to adverse effects of liver disease, encompassing coagulation dysfunction, altered metabolism of anesthesia and sedatives, immunologic dysfunction, hemorrhage related to varices, malnutrition and frailty, impaired wound healing, as well as diminished portal blood flow, overall hepatic circulation, and hepatic oxygen supply during surgical procedures. Therefore, a frequent clinical dilemma is whether surgical interventions should be pursued in patients with cirrhosis. Several risk scores are widely used to aid in the decision-making process, each with specific advantages and limitations. This review aims to discuss the preoperative risk factors in patients with cirrhosis, describe and compare surgical risk assessment models used in everyday practice, provide insights into the surgical risk according to the type of surgery and present recommendations for optimizing those with cirrhosis for surgical procedures. As the primary focus is on currently available risk models, the review describes the predictive value of each model, highlighting its specific advantages and limitations. Furthermore, for models that do not account for the type of surgical procedure to be performed, the review suggests incorporating both patient-related and surgery-related risks into the decision-making process. Finally, we provide an algorithm for the preoperative assessment of patients with cirrhosis before elective surgery as well as guidance perioperative management.

What came first, atypical hemolytic uremic syndrome or malignant hypertension: a clinical dilemma

What came first, atypical hemolytic uremic syndrome or malignant hypertension: a clinical dilemma

Diagnosing Polyomavirus Nephropathy without a Biopsy: Validation of the Urinary PyV-Haufen-Test in a Proof-of-Concept Study including Uromodulin Knock-out-Mice.

Polyomavirus nephropathy (PyVN) leads to kidney transplant dysfunction and loss. Since a definitive diagnosis requires an invasive kidney biopsy, a timely diagnosis is often hampered. In this clinical dilemma the PyV-haufen-test, centering around the detection of three-dimensional PyV aggregates in the urine, might provide crucial diagnostic information. A multistep experimental design. Hypothesis: PyV-haufen form within the kidneys under high concentrations of uromodulin, a kidney specific protein; PyV-haufen are kidney-specific-disease-markers. Investigative step A showed colocalization of uromodulin with aggregated PyV (i) in ten kidneys with PyVN by immunohistochemistry, (ii) in urine samples containing PyV-haufen by electron microscopy/immunogold labeling (n = 3), and (iii) in urine samples containing PyV-haufen by immunoprecipitation assays (n = 4). Investigative step B: In in-vitro experiments only high uromodulin concentrations of ≥ 1.25 mg/mL aggregated PyV, as is expected to occur within injured nephrons. In contrast, in voided urine samples (n = 59) uromodulin concentrations were below aggregation concentrations (1.2 -19.6 µg/mL). Investigative step C: 0/11 (0%) uromodulin KO-/- mice with histologic signs of PyVN showed urinary PyV-haufen shedding compared to 10/14 (71%) WT+/+ mice. PyV-haufen form within kidneys under high uromodulin concentrations. Thus, PyV-haufen detected in the urine are specific biomarkers for intra-renal disease, i.e. definitive PyVN.

Current Clinical Concepts: Nonoperative Management of Shoulder Instability.

Non-operative management following a shoulder dislocation or subluxation remains a challenging and complex task. Accurate diagnosis of the condition, and shared decision-making regarding operative and non-operative management, as well as timing of return to play is required. This clinical concept paper introduces a shoulder instability framework that addresses these fundamental clinical dilemmas. Valid clinical prognostic tools which can predict recurrent shoulder instability are reviewed. The process of shared decision-making within the realm of shoulder instability is also presented. Finally, a framework for progressive rehabilitation that addresses deficits in motor control, strength, and endurance in scapula and shoulder musculature is presented to guide patients from an initial instability event, through to return to play.

Consensus statement on the management of hyperkalaemia-An Asia-Pacific perspective.

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%-7% worldwide and 7%-10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high-risk patients. Conventional potassium-binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia-Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at-risk individuals; and (iii) correction of hyperkalaemia for at-risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region.

How should respiratory depression and loss of airway patency be handled during initiation of palliative sedation?

Loss of airway patency has been reported during initiation of palliative sedation. In present guidelines the loss of airway patency during initiation of palliative sedation is not addressed. Airway patency can be restored by jaw thrust/chin lift or placing the patient in the recovery position. A structured ethical analysis of how respiratory depression and loss of airway patency during initiation of palliative sedation should be handled. The essence of the dilemma is whether it is appropriate to apply simple non-invasive methods to restore airway patency in order to avoid the patient's immediate death. A structured analysis based on the four principles of healthcare ethics and stakeholders' interests. Beneficence and autonomy support a decision not to regain airway patency whereas non-maleficence lends weight to a decision to restore airway patency. Whether the proportionality criterion of the principle of double effect is met depends on the features of the individual case. The ethical problem appears to be a genuine dilemma where important values and arguments point to different conclusions. Whether to restore airway patency when the airway is obstructed during initiation of palliative sedation will ultimately be based on clinical judgment taking into account both any known patient preferences and relevant clinical information. There are strong arguments favoring both options in this clinical and ethical dilemma. The fact that a clear and universal recommendation cannot be made does not imply indifference regarding what is the clinically and ethically best option for each individual patient.

Achilles' Heel of currently approved immune checkpoint inhibitors: immune related adverse events.

Immunotherapy has revolutionized the cancer treatment landscape by opening up novel avenues for intervention. As the use of immune checkpoint inhibitors (ICIs) has exponentially increased, so have immune-related adverse events (irAEs). The mechanism of irAEs may involve the direct damage caused by monoclonal antibodies and a sequence of immune responses triggered by T cell activation. Common side effects include dermatologic toxicity, endocrine toxicity, gastrointestinal toxicity, and hepatic toxicity. While relatively rare, neurotoxicity, cardiotoxicity, and pulmonary toxicity can be fatal. These toxicities pose a clinical dilemma regarding treatment discontinuation since they can result in severe complications and necessitate frequent hospitalization. Vigilant monitoring of irAEs is vital in clinical practice, and the principal therapeutic strategy entails the administration of oral or intravenous glucocorticoids (GSCs). It may be necessary to temporarily or permanently discontinue the use of ICIs in severe cases. Given that irAEs can impact multiple organs and require diverse treatment approaches, the involvement of a multidisciplinary team of experts is imperative. This review aims to comprehensively examine the pathogenesis, clinical manifestations, incidence, and treatment options for various irAEs.

Characterizing acute and postsurgical pain management in patients receiving buprenorphine or buprenorphine/naloxone

BackgroundThere is currently a clinical dilemma in treating acute pain in patients receiving long-term buprenorphine products. MethodsThis is a retrospective cohort review involving patients receiving long-term buprenorphine therapy who either underwent a surgical procedure or presented to an emergency department (ED) for acute pain between January 1, 2012 and January 1, 2022. Patients were excluded if opioids were prescribed 30 days before the index date. Chart reviews were conducted to characterize buprenorphine treatment strategies and the addition of new pain medications. Chart review revealed (1) incidence of opioid use disorder (OUD) relapse, (2) hospital re-presentation for pain or OUD, (3) fatal and non-fatal overdose, and (4) all-cause mortality and suicidality. Descriptive statistics were used to analyze results. ResultsA total of 70 of 259 screened patients met inclusion criteria. The mean (±SD) age was 50.3 ± 13 years, 92.9% male, 64.3% White, and 78.6% had an OUD diagnosis. While 84.3% presented to the ED, 15.7% underwent surgical procedures. For the primary endpoint, the total daily dose of buprenorphine or buprenorphine/naloxone from index date to discharge was continued in 90.0%, increased in 2.9%, decreased in 1.4%, and discontinued in 5.7% of cases. At discharge, 46.2% were prescribed an additional pain medication. A total of 7.1% re-presented for pain or OUD relapse, 15.7% experienced an OUD relapse, 1.4% experienced new-onset suicidality, and 1.4% experience all-cause mortality within 90 days of the index date. No fatal or non-fatal opioid overdoses were observed. ConclusionThe most commonly observed practice was continuing buprenorphine doses in patients with acute or postsurgical pain, which was effective and safe. Although further data is necessary to fully elucidate these findings, the data herein may suggest that clinicians can safely continue buprenorphine doses in the acute pain setting in patients receiving these products chronically.

Insights into the management of Lewy body dementia: a scoping review

Lewy body dementia (LBD) is situated at the convergence of neurodegenerative disorders, posing an intricate and diverse clinical dilemma. The accumulation of abnormal protein in the brain, namely, the Lewy body causes disturbances in typical neural functioning, leading to a range of cognitive, motor, and mental symptoms that have a substantial influence on the overall well-being and quality of life of affected individuals. There is no definitive cure for the disease; however, several nonpharmacological and pharmacological modalities have been tried with questionable efficacies. The aim of this study is to figure out the role of different interventional strategies in the disease. Donepezil, rivastigmine, memantine, and galantamine were the commonly used drugs for LBD. Together with that, levodopa, antipsychotics, armodafinil, piracetam, and traditional medications like yokukansan were also used, when indicated. Talking about nonpharmacological measures, exercise, physical therapy, multicomponent therapy, occupational therapy, psychobehavioral modification, transcranial stimulation, and deep brain stimulation have been used with variable efficacies. Talking about recent advances in the treatment of LBD, various disease-modifying therapies like ambroxol, neflamapimod, irsenontrine, nilotinib, bosutinib, vodobatinib, clenbuterol, terazosin, elayta, fosgonimeton, and anle138b are emerging out. However, there drugs are still in the different phases of clinical trials and are not commonly used in clinical practice. With the different pharmacological and nonpharmacological modalities we have for treatment of LBD, all of them offer symptomatic relief only. Being a degenerative disease, definite cure of the disease can only be possible with regenerative measures.

Role of TGF-β3 in modulating inflammatory responses and wound healing processes in ischemic ulcers in atherosclerotic patients.

Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF-β3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF-β3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross-sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF-β3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF-β3, pro-inflammatory and anti-inflammatory markers. A subset of patients were administered topical TGF-β3 in order to evaluate its therapeutic effects. The expression pattern of TGF-β3 was found to be stage-dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF-β3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF-β3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF-β3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF-β3, which functions as an anti-inflammatory and pro-inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent.