Treatment Modalities Research Articles

In situ deposition of nanobodies by an engineered commensal microbe promotes survival in a mouse model of enterohemorrhagic E. coli

Abstract Engineered smart microbes that deliver therapeutic payloads are emerging as treatment modalities, particularly for diseases with links to the gastrointestinal tract. Enterohemorrhagic E coli (EHEC) is a causative agent of potentially lethal hemolytic uremic syndrome. Given concerns that antibiotic treatment increases EHEC production of Shiga toxin (Stx), which is responsible for systemic disease, novel remedies are needed. EHEC encodes a type III secretion system (T3SS) that injects Tir into enterocytes. Tir inserts into the host cell membrane, exposing an extracellular domain that subsequently binds intimin, one of its outer membrane proteins, triggering the formation of attaching and effacing (A/E) lesions that promote EHEC mucosal colonization. Citrobacter rodentium (Cr), a natural A/E mouse pathogen, similarly requires Tir and intimin for its pathogenesis. Mice infected with Cr(ΦStx2dact), a variant lysogenized with an EHEC-derived phage that produces Stx2dact, develop intestinal A/E lesions and toxin-dependent disease. Stx2a is more closely associated with human disease. By developing an efficient approach to seamlessly modify the C. rodentium genome, we generated Cr_Tir-MEHEC(ΦStx2a), a variant that expresses Stx2a and the EHEC extracellular Tir domain. We found that mouse pre-colonization with HS-PROT3EcT-TD4, a human commensal E. coli strain (E. coli HS) engineered to efficiently secrete- an anti-EHEC Tir nanobody, delayed bacterial colonization and improved survival after challenge with Cr_Tir-MEHEC(ΦStx2a). This study provides the first evidence to support the efficacy of engineered commensal E. coli to intestinally deliver therapeutic payloads that block essential enteric pathogen virulence determinants, a strategy that may serve as an antibiotic-independent antibacterial therapeutic modality.

Soluble immune checkpoint molecules in cancer risk, outcomes prediction, and therapeutic applications.

Immunotherapy has emerged as a pivotal modality in cancer treatment, with immune checkpoint inhibitors effectively combating malignancies by impeding crucial pathways within the immune system and stimulating patients' immune responses. Soluble forms of immune checkpoints exhibit a remarkable diversity and can be readily tracked in circulation, holding immense potential as biomarkers for cancer treatment. An increasing number of studies focused on soluble immune checkpoints in cancer have emerged thanks to technological advancements. In this systematic review, we comprehensively summarized the recent studies on soluble immune checkpoints in human cancer risk prediction, outcome prediction, therapeutic applications, and potential molecular mechanisms, which demonstrated the promising future of soluble immune checkpoints in clinical applications. The clinical relevance of soluble immune checkpoints has been recognized in multiple cancers, yet the therapeutic applications and mechanisms remain obscure. Interpreting the impacts and mechanisms of soluble immune checkpoints could shed a light on the novel strategies of cancer screening, treatments, and outcome prediction.

Influence of Postoperative Insulin Resistance on Short-Term Outcomes of Radical Gastrectomy for Gastric Cancer: A Microbiome and Metabolome-Based Prospective Cohort Study.

Gastrectomy is one of the main treatment modalities for gastric cancer (GC) and induces pathophysiological changes that significantly affect patients' postoperative recovery. In this study, we investigated the relationships between altered insulin resistance (IR), inflammation, and gut microbiota associated with gastrectomy. This study was a single-center prospective cohort investigation involving 60 patients with GC who underwent gastrectomy between May 2023 and April 2024. Monitoring encompassed IR, inflammation, and nutrition-related markers via blood assays, while gut microbiota analysis employed high-throughput sequencing, and short-chain fatty acids (SCFAs) were examined through targeted metabolomics. The study is registered under the number ChiCTR2300075653. The patients exhibited a significant increase in post-gastrectomy IR markers (P < 0.001), accompanied by elevated inflammation markers (P < 0.001), and also showeddecreased nutrition-related indicators (P < 0.001). Notable alterations were observed in the gut microbiota, including reductions in Bifidobacterium and Faecalibacterium, an increase in Streptococcus, and a noteworthy decrease in fecal butyrate. Patients with postoperative IR exhibited poorer inflammation markers (P < 0.05), nutritional indicators (P < 0.05), and postoperative recovery parameters (P < 0.05). Furthermore, significant negative correlations were observed between IR and Bifidobacterium,Faecalibacterium,as well as butyrate. Patients with GC post-gastrectomy displayed heightened IR, exacerbated inflammation, and compromised nutritional status. Disturbed gut microbiota and reduced fecal butyrate were observed. Gut microbiota and metabolite butyrate production may be predictors of postoperative IR and short-term outcomes in patients with GC.

Efficacy and safety of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pancreatic cancer peritoneal metastasis.

Pancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group. A retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS). A total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified. The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach.

Treatment Outcomes in Patients with Recurrent Adrenocortical Carcinoma.

While numerous studies have explored treatment outcomes for the overall ACC patient cohort, data on the subpopulation of patients with recurrent disease are limited. Therefore, the aim of this study was to assess treatment outcomes in patients with recurrent ACC. In this retrospective study, we included 18 patients median age 49 years (42-62); 67% female) diagnosed with recurrent ENSAT stage I-III ACC who underwent either R0 (n = 16) or Rx (n = 2) surgical resection of the tumor. The median time from the initial surgery to ACC recurrence was 29 months (IQR 18-50). Seven patients (39%) manifested local recurrence, while 11 patients (61%) developed distant metastases. The median follow-up duration after tumor recurrence was 32 months (IQR 25-53). Regarding the treatment of ACC recurrence, 10 patients underwent a second surgery either as an alone procedure (n = 4), or in combination with mitotane (n = 4), mitotane and chemotherapy (n = 1), or mitotane combined with radiotherapy (n = 1). The remaining patients received treatment involving chemotherapy±mitotane (n = 4) and locoregional therapy ±chemotherapy (n = 3). One patient chose not to proceed with further management and follow-up. The median PFS was 17 (95% CI 8-26) months while the median OS was not reached. In the multivariate model, increased mortality was associated with advanced age (p = 0.04) and a shorter interval to ACC recurrence (p = 0.03). A significant proportion of patients with ACC recurrence experience disease progression or second recurrence, despite all treatment efforts. Nevertheless, by integrating diverse treatment modalities, many patients have the potential to attain long-term survival.

Role of Low Dose Intravenous Methylprednisolone in Pulmonary Hemorrhage Associated with Severe Leptospirosis

Leptospirosis, an emerging zoonosis endemic in Malaysia, presents with diverse clinical manifestations, ranging from mild to potentially fatal illness. Pulmonary involvement in leptospirosis, particularly pulmonary hemorrhage, poses a significant risk of mortality, prompting exploration of various treatment strategies. While high-dose corticosteroid therapy has demonstrated efficacy in some studies, data on the use of low-dose corticosteroids in pulmonary leptospirosis remain scarce. Here, we report a case of successful treatment with low-dose methylprednisolone in a patient diagnosed with Weil’s disease and pulmonary hemorrhage. The patient, initially presenting with fever, vomiting and hemoptysis, rapidly deteriorated, necessitating intubation due to respiratory distress. Prompt initiation of low-dose methylprednisolone alongside antibiotic therapy resulted in clinical improvement, resolution of pulmonary hemorrhage, and normalization of laboratory parameters. This case highlights the potential efficacy of low-dose corticosteroid therapy in managing severe pulmonary involvement in leptospirosis, offering insights into alternative treatment modalities for this challenging condition. Further studies are warranted to elucidate the optimal dosing and timing of corticosteroid therapy in leptospirosis-associated pulmonary complications.

Predictors of quality of life, economic impact, and loss to follow-up after open tibial shaft fractures in Ghana.

Open tibia fractures are associated with substantial morbidity and impact on quality of life. Despite increasing incidence in low-resource settings, most open tibia fracture research comes from high-resource settings. This study aimed to assess the impact of socioeconomic status on treatment modality and evaluate predictors of health-related quality of life following open tibia fractures in Ghana. A single-center prospective observational study was conducted in Kumasi, Ghana, from May 2020 to April 2022. Adults with open tibial shaft fractures presenting within 2 weeks of injury were eligible. Demographics, comorbidities, socioeconomic factors, and hospital course were collected at enrollment. Follow-up was scheduled at 8, 12, 26, and 52 weeks. A telephone survey assessing reasons for loss to follow-up was initiated on enrollment completion. A total of 180 patients were enrolled. Most patients were employed before injury (79.9%), had government insurance (67.2%), and were from rural areas (59.4%). Fracture classification was primarily Gustilo-Anderson type 3A (49.1%). No relationship between socioeconomic predictors and treatment modality was identified. The largest barriers to follow-up were preference for bonesetter treatment (63.1%), treatment cost (48.8%), and travel cost (29.8%). Of the lost to follow-up patients contacted, 67 (79.8%) reported receiving traditional bonesetter care. Reasons for seeking traditional bonesetter care included ease of access (83.6%), lower cost (77.6%), and familial influence (50.7%). No association was identified between socioeconomic predictors and choice of treatment. Bonesetter treatment plays a substantial role in the care of open tibia fractures in Ghana, largely because of ease of access and lower cost.

Anterior Cruciate Ligament Tears in Soccer Players.

Anterior cruciate ligament (ACL) injuries to soccer players present unique challenges in sports medicine, given the sport's global prevalence and intricate injury dynamics. These injuries, especially in the youth and female demographic, have become a substantial concern in sports medicine. This review explores the epidemiology, mechanism of injury, diagnostic procedures, treatment modalities, and rehabilitation strategies related to ACL tears within the soccer community. Progress in diagnostics, treatments, and rehabilitation underscores the importance of evidence-based approaches. As soccer continues its ascent in popularity, addressing the specific risks and nuances of ACL injuries in this context remains of paramount significance.

Chasing New Cancer Treatments: Current Status and Future Development of Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is expected to be a promising next-generation cancer treatment. In 2020, Japan, which has led the research on this treatment modality, was the first country in the world to approve BNCT. The boron agents that have been clinically applied in BNCT include a caged boron compound (mercaptoundecahydrododecaborate: BSH) and a boron-containing amino acid (p-boronophenylalanine: BPA). In particular, the BPA preparation Steboronine® is the only approved drug for BNCT. However, the problem with BPA is that it is poorly retained in the tumor and has very low solubility in water. This cannot be overlooked for BNCT, which requires large amounts of boron in the tumor. The high dosage volume, together with low tumor retention, leads to reduced therapeutic efficacy and increased physical burden on the patient. In the case of BSH, its insufficient penetration into the tumor is problematic. Based on drug delivery system (DDS) technology, we have developed a next-generation boron pharmaceutical superior to Steboronine®. Our approach involves the redevelopment of BPA using innovative ionic liquid formulation technology. Here, we describe previous boron agents and introduce our recent efforts in the development of boron compounds.

Malignancy in systemic lupus erythematosus: relation to disease characteristics in 92 patients - a single center retrospective study.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a variable clinical manifestation, potentially leading to death. Importantly, patients with SLE have an increased risk of neoplastic disorders. Thus, this study aimed to comprehensively evaluate the clinical and laboratory characteristics of patients with SLE and with or without malignancy. We conducted a retrospective analysis of medical records of 932 adult Caucasian patients with SLE treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected demographic, clinical, and laboratory characteristics, but also treatment modalities with disease outcomes. Among 932 patients with SLE, malignancy was documented in 92 (9.87%), with 7 (7.61%) patients experiencing more than one such complication. Non-hematologic malignancies were more prevalent (n = 77, 83.7%) than hematologic malignancies (n = 15, 16.3%). Patients with SLE and malignancy had a higher mean age of SLE onset and a longer mean disease duration than patients without malignancy (p < 0.001 and p = 0.027, respectively). The former group also presented more frequently with weight loss (odds ratio [OR] = 2.62, 95% confidence interval [CI] 1.61-4.23, p < 0.001), fatigue/weakness (OR = 2.10, 95% CI 1.22-3.77, p = 0.005), and fever (OR = 1.68, 95% CI 1.06-2.69, p = 0.024). In the malignancy-associated group, we noticed a higher prevalence of some clinical manifestations, such as pulmonary hypertension (OR = 3.47, 95% CI 1.30-8.42, p = 0.007), lung involvement (OR = 2.64, 95% CI 1.35-4.92, p = 0.003) with pleural effusion (OR = 2.39, 95% CI 1.43-3.94, p < 0.001), and anemia (OR = 2.24, 95% CI 1.29-4.38, p = 0.006). Moreover, the patients with SLE and malignancy more frequently had internal comorbidities, including peripheral arterial obliterans disease (OR = 3.89, 95% CI 1.86-7.75, p < 0.001), myocardial infarction (OR = 3.08, 95% CI 1.41-6.30, p = 0.003), heart failure (OR = 2.94, 95% CI 1.30-6.17, p = 0.005), diabetes mellitus (OR = 2.15, 95% CI 1.14-3.91, p = 0.011), hypothyroidism (OR = 2.08, 95% CI 1.29-3.34, p = 0.002), arterial hypertension (OR = 1.97, 95% CI 1.23-3.23, p = 0.003), and hypercholesterolemia (OR = 1.87, 95% CI 1.18-3.00, p = 0.006). Patients with SLE and malignancy were treated more often with aggressive immunosuppressive therapies, including cyclophosphamide (OR = 2.07, 95% CI 1.30-3.28, p = 0.002), however median cumulative cyclophosphamide dose in malignancy-associated SLE subgroup was 0g (0-2g). Interestingly, over a median follow-up period of 14 years (ranges: 8-22 years) a total of 47 patients with SLE died, with 16 cases (5.28%) in the malignancy-associated SLE group and 31 cases (5.73%) in the non-malignancy SLE group (p = 0.76). The most common causes of death were infections (21.28%) and SLE exacerbation (8.51%). The study highlights the relatively frequent presence of malignancies in patients with SLE, a phenomenon that demands oncological vigilance, especially in patients with a severe clinical course and comorbidities, to improve long-term outcomes in these patients.

A cross-temporal multimodal fusion system based on deep learning for orthodontic monitoring

IntroductionIn the treatment of malocclusion, continuous monitoring of the three-dimensional relationship between dental roots and the surrounding alveolar bone is essential for preventing complications from orthodontic procedures. Cone-beam computed tomography (CBCT) provides detailed root and bone data, but its high radiation dose limits its frequent use, consequently necessitating an alternative for ongoing monitoring. ObjectivesWe aimed to develop a deep learning-based cross-temporal multimodal image fusion system for acquiring root and jawbone information without additional radiation, enhancing the ability of orthodontists to monitor risk. MethodsUtilizing CBCT and intraoral scans (IOSs) as cross-temporal modalities, we integrated deep learning with multimodal fusion technologies to develop a system that includes a CBCT segmentation model for teeth and jawbones. This model incorporates a dynamic kernel prior model, resolution restoration, and an IOS segmentation network optimized for dense point clouds. Additionally, a coarse-to-fine registration module was developed. This system facilitates the integration of IOS and CBCT images across varying spatial and temporal dimensions, enabling the comprehensive reconstruction of root and jawbone information throughout the orthodontic treatment process. ResultsThe experimental results demonstrate that our system not only maintains the original high resolution but also delivers outstanding segmentation performance on external testing datasets for CBCT and IOSs. CBCT achieved Dice coefficients of 94.1 % and 94.4 % for teeth and jawbones, respectively, and it achieved a Dice coefficient of 91.7 % for the IOSs. Additionally, in the context of real-world registration processes, the system achieved an average distance error (ADE) of 0.43 mm for teeth and 0.52 mm for jawbones, significantly reducing the processing time. ConclusionWe developed the first deep learning-based cross-temporal multimodal fusion system, addressing the critical challenge of continuous risk monitoring in orthodontic treatments without additional radiation exposure. We hope that this study will catalyze transformative advancements in risk management strategies and treatment modalities, fundamentally reshaping the landscape of future orthodontic practice.

Phytochemicals and their Potential Mechanisms against Insulin Resistance.

Insulin's inception dates back to 1921 and was unveiled through a momentous revelation. Diabetes is a dangerous, long-term disease in which the body fails to generate enough insulin or utilize the insulin it creates adequately. This causes hyperglycemia, a state of high blood sugar levels, which can even put a person into a coma if not managed. Activation of the insulin receptor corresponds to two crucial metabolic functions, i.e., uptake of glucose and storage of glycogen. Type 2 diabetes mellitus (T2DM) exists as one of the most challenging medical conditions in the 21st century. The sedentary lifestyle and declining quality of food products have contributed to the rapid development of metabolic disorders. Hence, there is an urgent need to lay some reliable, significant molecules and modalities of treatment to combat and manage this epidemic. In this review, we have made an attempt to identify and enlist the major phytoconstituents along with the associated sources and existing mechanisms against insulin resistance. The conducted study may offer potential sustainable solutions for developing and formulating scientifically validated molecules and phytoconstituents as formulations for the management of this metabolic disorder.

Digital clinics for diagnosing and treating migraine.

Several innovative digital technologies have begun to be applied to diagnosing and treating migraine. We reviewed the potential benefits and opportunities from delivering migraine care through comprehensive digital clinics. There are increasing applications of digitization to migraine diagnosis and management, including e-diaries, and patient self-management, especially after the COVID-19 pandemic. Digital care delivery appears to better engage chronic migraine sufferers who may struggle to present to physical clinics. Digital clinics appear to be a promising treatment modality for patients with chronic migraine. They potentially minimize travel time, shorten waiting periods, improve usability, and increase access to neurologists. Additionally, they have the potential to provide care at a much lower cost than traditional physical clinics. However, the current state of evidence mostly draws on case-reports, suggesting a need for future randomized trials comparing digital interventions with standard care pathways.

Femoroacetabular Impingement and Groin Injuries Among Soccer Players.

Groin injuries and femoroacetabular impingement are common among soccer players and can provide a challenge in diagnosis, as well as treatment. Nonoperative and operative measures are the 2 predominant treatments. This current review investigates the recent literature on groin and femoroacetabular impingement injuries in soccer players, as well as potential treatment modalities.

49158 Examination of Medicaid Insurance as a barrier to patient choice in scalp psoriasis treatment modalities in the African American population

49158 Examination of Medicaid Insurance as a barrier to patient choice in scalp psoriasis treatment modalities in the African American population

New diagnostic and nonsurgical local treatment modalities for early stage lung cancer

New diagnostic and nonsurgical local treatment modalities for early stage lung cancer

Ketamine Therapy in Patients of Alcohol Use Disorder: A Prospective Pilot Study to Evaluate Abstinence Rate with This Add-on Treatment Modality

Background: Alcohol use disorders (AUDs) are emerging as a substance use disorder having various psychological and physical ill effects leading to hampering of individual’s productivity and functioning. Aims: The aim of this study was to evaluate the efficacy of ketamine in enhancing confidence levels to abstain from alcohol. Methods: Eighteen patients were administered ketamine intravenously after detoxification; a total of three doses, with a 3-day gap between each. The Alcohol Abstinence Self-Efficacy Scale was used to measure their confidence in abstaining from alcohol. Results: The study revealed a significant increase in mean confidence scores after three ketamine sessions, with a final assessment showing a 51.98% increase in confidence from baseline. Conclusions: The study found that ketamine therapy significantly increased confidence levels in individuals with AUD to abstain from alcohol, with P = 0.05 threshold. However, the impact may wane over time, suggesting the need for additional support or maintenance treatments.

Effects of Glucosamine in the Temporomandibular Joint Osteoarthritis: A Review.

Osteoarthritis in the temporomandibular joint (TMJ) is a chronic disease characterized by irreversible damage to articular surfaces, including inflammation, loss of articular cartilage, and subchondral bone alterations, which would be radiographically evident only in later stages. Symptomatic slow-acting so-called nutraceutical drugs have been proposed as a treatment for osteoarthritis in comparison to non-steroidal anti-inflammatory drugs (NSAID) because of their appreciable safety profile even in long-term intake. Glucosamine, being one among them, proved highly efficient in knee osteoarthritis. However, its application in TMJ osteoarthritis dates back only to 2001 and is still inconclusive in its efficiency even with systematic reviews, in restoring the structural and functional aspects of damaged TMJ. Glucosamine, being a natural compound and also a contributor to building the matrix of articular cartilage, can be utilized effectively for TMJ osteoarthritis as an adjunct along with other conventional treatment modalities available till now, which also have moderate prognosis in most of the clinical scenarios. This review summarizes data relating to the mechanism of osteoarthritis and its management using glucosamine formulations. The beneficial effects of glucosamine on the pathophysiology of TMJ osteoarthritis are possibly due to its contribution to hyaluronic acid regulation and in establishing a proper balance between anabolism/catabolism in the articular tissues.

Exercise interventions for mitigating the persistent side effects of COVID-19

AbstractFollowing infection with Sars-Cov2, a significant proportion of patients suffer from long-term symptoms afflicting many of the body’s systems. The understanding of these sequelae is still evolving, and as of the present diagnostic techniques and symptom management are still developing to effectively combat the wide variety of long-term symptoms. Many of the long-term symptoms observed following cases of COVID-19 are present in other chronic illnesses, and exercise intervention has been observed as a potent therapy for the alleviation of many of those symptoms. However, the effects of exercise regimens in the treatment of long COVID symptoms are not well documented, and there is little information regarding the nature of those interventions. A review of the available literature was conducted to determine the nature of the post-acute sequelae of COVID-19 (PASC) and identify the potential impact exercise intervention could have in alleviating these sequelae. Overall, intensity and modality of treatment are paramount to the success of a multifaceted exercise intervention to provide the greatest benefits to patients suffering from PASC. There are some limitations to the provision of exercise therapy as an intervention for COVID-19 patients, but nonetheless the benefits of exercise are sufficient that further research is implicated.

Assessment and Rehabilitation Strategies for Sports-Related Musculoskeletal Injuries

This study provides a comprehensive analysis of assessment methods and rehabilitation techniques for sports activities-related musculoskeletal accidents. Understanding the complexity and variety of injuries incurred in sports, this paper synthesizes the modern-day evidence-based practices and protocols used to assess such injuries. Assessment processes embody a multidimensional exam, consisting of physical examination techniques, imaging modalities, and practical checks, aiming to diagnose the extent and nature of the harm precisely. Furthermore, the evaluation examines into rehabilitation strategies tailor-made to precise accidents, emphasizing the importance of a holistic approach that integrates therapeutic physical activities, manual therapy, neuromuscular re-schooling, and modern loading protocols. A minimum of 200 participants, comprising athletes with various types of musculoskeletal injuries, will be recruited to ensure diversity and generalizability of findings. Participants will be randomly assigned to intervention and control groups using computer-generated random numbers to ensure an unbiased allocation process. Stratification based on injury type and severity will be employed as a criteria, ensuring a balanced distribution of participants across different categories. Participants will undergo rehabilitation sessions three times per week for a duration of eight weeks, ensuring a structured and progressive approach to musculoskeletal injury recovery. Special attention is given to individualized rehabilitation plans that consider the athlete's sport-specific needs, biomechanics, and psychological aspects, facilitating the most beneficial restoration and secure return to play. The paper concludes by highlighting the ongoing advancements in generation and treatment modalities that similarly enhance the evaluation accuracy and efficacy of rehabilitation interventions for sports-related musculoskeletal injuries, emphasizing the importance of a comprehensive and customized method in the management of such injuries.