One-day surgery is safe and effective in unicompartmental knee arthroplasty: A prospective comparative study at 1 year of follow-up.

PURPOSE: To compare the outcomes and complications of two perioperative protocols for the management of patients who underwent medial unicompartmental knee arthroplasty (UKA): 24 h (1-day surgery [OS]) versus 72 h (enhanced recovery after surgery [ERAS]) of the length of hospital stay (LOS). In our hypothesis, the reduction of the LOS from 3 to 1 day did not influence the outcomes and complications. METHODS: A total of 42 patients (21 in each group) with isolated anteromedial knee osteoarthritis and meeting specific criteria were prospectively included in the study. Clinical outcomes included Knee Society Score (KSS) and Forgotten joint score while pain evaluation was performed using a Visual Analogue Scale (VAS). Functional outcomes were assessed measuring the knee range of motion (ROM) while radiographic outcomes were evaluated measuring the amelioration of the varus deformity through the hip-knee-ankle angle (HKA). RESULTS: Clinical and functional outcomes did not significantly differ between the two groups. Complications occurred in 9.5% of OS and 4.7% of ERAS group patients. Significant improvements in knee ROM, VAS pain, KSS and HKA angle were observed postsurgery, with no significant differences between groups except in KSS expectations and function trends. CONCLUSION: The OS protocol is safe and effective and LOS, in a well-defined fast-track protocol, did not significantly impact clinical and functional outcomes. OS may lead to reduced hospitalisation costs and potential reductions in complications associated with prolonged stays, benefiting both patients and healthcare facilities. However, further research with larger sample sizes and longer follow-up periods is needed to confirm these findings. Early mobilisation and rehabilitation protocols are key components of successful patient recovery following UKA procedures. LEVEL OF EVIDENCE: Level II.

Reassessing type 2 diabetes in adolescents and its management strategies based on insulin resistance.

With changes in lifestyle behaviors, including dietary structure and habits, the prevalence of Youth-onset Type 2 Diabetes Mellitus (YODM) has increased 2 to 3 times compared to 30 years ago. YODM patients experience complications earlier, progress faster, and exhibit more severe symptoms. However, limited and inconclusive direct evidence, coupled with poor patient compliance, poses challenges in the clinical management of YODM. Apart from the continuous decline in pancreatic ß-cell function and quantity, tissue-specific insulin resistance (IR) is also a typical characteristic of YODM. The main mechanisms of IR in YODM involve different aspects such as obesity, dietary imbalance, abnormal substance metabolism, chronic inflammation, oxidative stress, and hormonal fluctuations during adolescence. For the comprehensive management of YODM, besides achieving good control of blood glucose levels, it may be necessary to apply the most appropriate methods considering the uniqueness of the patient population and the specifics of the disease. Early identification and detection of the disease are crucial. Precise screening of patients with well-functioning pancreatic insulin ß-cells, primarily characterized by IR and obesity, represents the population most likely to achieve diabetes remission or reversal through lifestyle modifications, medications, or even surgical interventions. Additionally, considering potential emotional disorders or the impact of adolescent hormones in these patients, health education for patients and caregivers is essential to make them aware of the long-term benefits of well-controlled blood glucose. In conclusion, adopting comprehensive management measures to achieve diabetes remission or reversal is the ideal goal. Controlling high blood glucose, obesity, and other risk factors related to diabetes complications is the next priority to delay the occurrence and progression of complications. A comprehensive perspective on IR provides insights and references for identifying YODM and its management strategies.

Laparoscopic excision of a large retroperitoneal cyst: Case report and literature review.

Retroperitoneal cysts, a rare surgical phenomenon, present diagnostic challenges due to their typically asymptomatic nature. A 62-year-old male presented with a 4-month history of abdominal distension and increased burping. Upon clinical examination, a soft, distended, nontender abdomen with a palpable mass extending from the epigastric region to 3 cm below the umbilicus was revealed. Imaging revealed a 14.6 cm × 15.8 cm × 16.4 cm nonenhancing retroperitoneal lesion, compressing the right ureter and causing mild right hydronephrosis. Multiple gall bladder calculi, an umbilical hernia, and lipomatous lesions associated with adrenal glands were also discovered. Laparoscopic retroperitoneal cystectomy, cholecystectomy, and umbilical hernia repair were performed. Intraoperatively, 150 ml ascitic fluid and 1200 ml cystic fluid were found. This case highlights the intricate clinical presentation of a retroperitoneal cyst, emphasizing the need for surgical exploration. Successful laparoscopic management contributes to the evolving understanding of optimal treatment strategies.

Diagnosis and management of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic and relapsing immune-mediated disease of the gastrointestinal tract with a gradually increasing global incidence and prevalence. A prolonged course of IBD leads to a decline in patient quality of life and the creation of a substantial economic burden on society. Owing to the lack of specific diagnostic markers, the diagnosis of IBD still needs a gold standard based on a combination of clinical manifestations, imaging, laboratory, and endoscopic results. Accordingly, the current goals of IBD treatment are to alleviate clinical symptoms and reduce recurrence rates. Therefore, it is imperative to develop a standard set of procedures to diagnose and treat IBD. In this review, we summarize prominent and emerging studies, outline classical and contemporary approaches to diagnosing and managing IBD, and integrate multiple guidelines. Furthermore, we propose the possibility of establishing an early and comprehensive diagnostic workflow and personalized management strategy in the future. We aim to enhance the quality and standardization of diagnostic and treatment procedures for IBD.

Unraveling the Tapestry of Pain: A Comprehensive Review of Ethnic Variations, Cultural Influences, and Physiological Mechanisms in Pain Management and Perception.

The medical management of pain is a nuanced challenge influenced by sociocultural, demographic, and ethical factors. This review explores the intricate interplay of these dimensions in shaping pain perception and treatment outcomes. Sociocultural elements, encompassing cultural beliefs, language, societal norms, and healing practices, significantly impact individuals' pain experiences across societies. Gender expectations further shape these experiences, influencing reporting and responses. Patient implications highlight age-related and socioeconomic disparities in pain experiences, particularly among the elderly, with challenges in managing chronic pain and socioeconomic factors affecting access to care. Healthcare provider attitudes and biases contribute to disparities in pain management across racial and ethnic groups. Ethical considerations, especially in opioid use, raise concerns about subjective judgments and potential misuse. The evolving landscape of placebo trials adds complexity, emphasizing the importance of understanding psychological and cultural factors. In conclusion, evidence-based guidelines, multidisciplinary approaches, and tailored interventions are crucial for effective pain management. By acknowledging diverse influences on pain experiences, clinicians can provide personalized care, dismantle systemic barriers, and contribute to closing knowledge gaps, impacting individual and public health, well-being, and overall quality of life.

Maternal and Perinatal Outcomes in Placenta Previa: A Comprehensive Review of Evidence.

Placenta previa poses significant risks to maternal and perinatal health, yet its management remains challenging. This comprehensive review synthesizes current evidence on maternal and perinatal outcomes in placenta previa, addressing its epidemiology, pathophysiology, diagnosis, and management strategies. Placenta previa complicates pregnancies, with increasing incidence linked to factors such as advanced maternal age and rising cesarean rates. Maternal complications, including hemorrhage and placenta accreta spectrum disorders, pose substantial risks. At the same time, perinatal outcomes are marked by increased rates of preterm birth, intrauterine growth restriction, and neonatal morbidity and mortality. Timely diagnosis and appropriate management, including antenatal corticosteroids and multidisciplinary care, are critical for optimizing outcomes. Future research should focus on improving diagnostic methods, evaluating novel interventions, and assessing long-term neurodevelopmental outcomes. This review underscores the importance of informed clinical practice and ongoing research efforts to enhance outcomes for women and infants affected by placenta previa.

Weight Loss Programs: Why Do They Fail? A Multidimensional Approach for Obesity Management.

PURPOSE OF REVIEW: Despite the prevalence of weight loss programs, their success rates remain discouraging, with around half of individuals regaining lost weight within two years. The primary objective of this review is to explore the factors contributing to the failure of weight loss programs and to provide insights into effective weight management strategies. RECENT FINDINGS: Factors contributing to the failure of weight loss programs include the impracticality of restrictive diets, potential metabolic impacts, limited focus on lifestyle changes, genetic predispositions, psychological influences, socioeconomic status, and medical conditions. A holistic approach considering these factors is crucial for safe and sustainable weight loss. Key findings indicate the importance of holistic approaches to weight management, including lifestyle modifications, medical interventions, and behavioral and psychological strategies. Effective weight loss strategies emphasize low-calorie, nutrient-rich diets, regular physical activity, and interventions tailored to individual needs. Combining multiple approaches offers the best chance of successful weight management and improved health outcomes. This review provides insights into the complexities of obesity management and the factors contributing to the failure of weight loss programs. It highlights the necessity of adopting a holistic approach that addresses dietary habits, physical activity, genetic factors, psychological well-being, and socioeconomic influences. Recommendations include implementing lifestyle modifications, medical interventions when necessary, and integrating behavioral and psychological support to achieve sustainable weight loss and mitigate the global health challenge posed by obesity.

Mode of inheritance for pesticide resistance, importance and prevalence: A review.

Pesticides remain a cornerstone in pest control, yet their extensive and irrational use also fuel the evolution of resistance. This review analyzes globally published experimental data spanning from the 1970s to 2023 to focus on how phenotypic and underlying genotypic variations are shaped during the selective response. The discussion commences with an examination of sex-linked/maternal resistance. Observations related to maternal inheritance have enriched our understanding of pesticide mode of action, notably exemplified by bifenazate. However, the predominant control of the resistant phenotype is attributed to autosomal traits, with a high prevalence of dominance and monogenic inheritance observed, also evident in field strains. This observation raises concerns regarding resistance management strategies due to their potential to accelerate the spread of resistance. The interplay between dominance levels and monogenic inheritance is further explored, with dominant traits being significantly more prevalent in polygenic inheritance. This observation may be attributed to the accumulation of enhanced metabolism. Notably, further analysis indicated that field strains exhibit a higher incidence of monogenic inheritance compared to other selected strains, aligning with established theoretical frameworks. In conclusion, the genetic architecture of resistance warrants increased research focus for its pivotal role in guiding resistance management strategies and advancing fundamental research.

Multidisciplinary Management Strategies for Long COVID: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness, skin rashes, and cardiac, endocrine, renal and hepatic manifestations. The treatment of this syndrome remains challenging. A multidisciplinary approach to address combinations of symptoms affecting multiple organ systems has been widely adopted. This narrative review aims to bridge the gap surrounding the broad treatment approaches by providing an overview of multidisciplinary management strategies for the most common long COVID conditions.

Exploring the ethnobiological practices of fire in three natural regions of Ecuador, through the integration of traditional knowledge and scientific approaches.

This study examines the convergence between traditional and scientific knowledge regarding the use of fire and its potential to trigger wildfires, with possible impacts on ecosystems and human well-being. The research encompasses three distinct natural regions of Ecuador: the coast, the highlands, and the Amazon. Data on traditional fire use were collected through semi-structured interviews with 791 members from five local communities. These data were compared with climatic variables (rainfall (mm), relative humidity (%), wind speed (km/h), and wind direction) to understand the climatic conditions conducive to wildfires and their relationship with human perceptions. Furthermore, the severity of fires over the past 4 years (2019-2022) was assessed using remote sensing methods, employing the Normalized Burn Ratio (NBR) and the difference between pre-fire and post-fire conditions (NBR Pre-fire-NBR Post-fire). The results revealed a significant alignment between traditional knowledge, climatic data, and many fires, which were of low severity, suggesting potential benefits for ecosystems. These findings not only enable the identification of optimal techniques and timing for traditional burns but also contribute to human well-being by maintaining a harmonious balance between communities and their environment. Additionally, they provide valuable insights for the development of more inclusive and effective integrated fire management strategies in these natural areas of Ecuador.

Environmental and Human Health Problems Associated with Hospital Wastewater Management in Zimbabwe.

PURPOSE OF THE REVIEW: Wastewater is a term used to describe water that has undergone degradation in quality owing to anthropogenic activities or natural processes. Wastewater encompasses liquid waste originating from academic institutions, households, agricultural sector, industries, mines and hospitals. Hospital wastewater contains potentially hazardous substances including residues of pharmaceuticals, radioisotopes, detergents and pathogens, with detrimental impacts to the environment and human health. Nevertheless, studies related to hospital waste management are limited in Africa, particularly in Southern Africa. This research offers an overview of aspects surrounding hospital wastewater in Southern Africa, focusing on Zimbabwe. Already published and grey literature was reviewed to compile the paper. RECENT FINDINGS: Number of patients, nature of medical services offered and hospital size influences generation of hospital wastewater. Partially and non-treated hospital wastewater is managed together with municipal wastewater. Management of hospital wastewater is impeded by shortage of resources, lack of co-ordination among responsible authorities and ineffective legal framework enforcement, among other challenges. Inappropriate hospital wastewater management results in environmental contamination, causing human ailments. Attainment of sustainable hospital wastewater management requires clearly defined and enforced legislation, collaboration of accountable stakeholders, sufficient resources and enhanced awareness of involved stakeholders. Application of technologies that uphold recycling and reuse of wastewater is essential to reach Sustainable Development Goals, Zimbabwe Vision 2030 and National Development Strategy 1 targets, particularly those dealing with environmental protection while upholding human health.

Neurological Conundrum: A Case of Cerebellar Hemispheric Enlargement and Atypical Symptoms.

Cerebellar hemispheric enlargement with atypical neurological symptoms poses diagnostic challenges in clinical practice. We present the case of a 57-year-old female with persistent headache, left facial paraesthesia, dysarthria, gait ataxia, and longstanding neck swelling. Imaging studies revealed enlargement of the left cerebellar hemisphere with associated mass effect and compression of adjacent structures. The underlying etiology remained uncertain despite extensive evaluation, including magnetic resonance imaging and angiography. Differential diagnoses included neoplastic, vascular, inflammatory, and metabolic etiologies, but none fully accounted for the clinical findings. Management strategies focused on symptomatic relief and close monitoring. This case underscores the complexity of diagnosing and managing patients with rare neurological manifestations and highlights the need for continued research and collaborative approaches in optimising patient care.

Navigating Perinatal Challenges: A Comprehensive Review of Cholestasis of Pregnancy and Its Impact on Maternal and Fetal Health.

Cholestasis of pregnancy (CP), or intrahepatic CP (ICP), represents a condition peculiar to pregnancy, marked by impaired bile acid flow and consequent accumulation in the maternal bloodstream. Primarily emerging in the third trimester, CP is linked with considerable risks to both the mother and fetus, including heightened incidences of preterm birth, fetal distress, and stillbirth, alongside maternal complications such as intense pruritus and liver dysfunction. Despite its clinical significance, the etiology of CP, which involves genetic, hormonal, and environmental factors, remains partially understood. This comprehensive review delves into the physiology and pathophysiology of CP, outlines its clinical manifestations and diagnostic criteria, and discusses the associated maternal and fetal complications. Furthermore, it evaluates current management strategies, prognostic implications, and potential long-term effects on maternal and child health. It also explores future research directions, emphasizing the need for advancements in understanding the pathophysiology of CP, developing novel therapeutic interventions, and improving risk stratification models. By offering a thorough overview of CP, this review aims to enhance clinical awareness, guide management practices, and identify areas requiring further investigation, ultimately contributing to better health outcomes for affected women and their babies.

Spontaneous haemoperitoneum in pregnancy in women with endometriosis: Diagnostic challenges and management strategies.

Spontaneous haemoperitoneum in pregnancy is a rare but potentially life-threatening condition that requires prompt recognition and management to avert a catastrophic outcome for the mother and baby. The main aim of this review is to summarise the current knowledge on this topic, including its incidence and clinical presentation, highlight the diagnostic challenges, and suggest management strategies. To achieve our objective, we examine the existing literature to provide insights into this complex clinical presentation to enhance our understanding and, in so doing, contribute to the existing body of knowledge on the subject of spontaneous haemoperitoneum in pregnancy.

American Academy of Dermatology Guidelines for Managing Atopic Dermatitis.

The American Academy of Dermatology first published a series of guidelines for diagnosing and managing atopic dermatitis in 2014. Twelve clinicians were selected to review, grade, and offer clinical insight on available data regarding the clinical features, symptomology, pathophysiology, education, treatment, and emerging clinical studies on atopic dermatitis (AD). Based on these findings, the AAD released a guideline to streamline information on atopic dermatitis for physicians, recommending using clinical evidence to diagnose and first treating with nonpharmacologic therapies to restore the natural skin barrier. Topical pharmacologic therapies were recommended for improving pruritus and inflammation and newer systemic agents for clinically relevant moderate-to-severe cases. Evidence-based practices were emphasized in comparison to those that lacked therapeutic data. To highlight the emerging evidence and pharmacologic breakthroughs in atopic dermatitis, the AAD produced an updated set of guidelines educating physicians on new agents and their role in treatment. This chapter reviews the AAD guidelines as a tool for managing atopic dermatitis and staying up to date on disease advancements.

Biosecurity risks to human food supply associated with plant-parasitic nematodes.

Biosecurity in agriculture is essential for preventing the introduction and spread of plant-parasitic nematodes (PPNs) which threaten global food security by reducing crop yields and facilitating disease spread. These risks are exacerbated by increased global trade and climate change, which may alter PPN distribution and activity, increasing their impact on agricultural systems. Addressing these challenges is vital to maintaining the integrity of the food supply chain. This review highlights significant advancements in managing PPN-related biosecurity risks within the food supply chain, particularly considering climate change's evolving influence. It discusses the PPN modes of transmission, factors increasing the risk of infestation, the impact of PPNs on food safety and security, and traditional and emerging approaches for detecting and managing these pests. Literature suggests that implementing advanced biosecurity measures could decrease PPN infestation rates by up to 70%, substantially reducing crop yield losses and bolstering food security. Notably, the adoption of modern detection and management techniques, (molecular diagnostics and integrated pest management) and emerging geospatial surveillance and analysis systems (spectral imaging, change-detection analysis) has shown greater effectiveness than traditional methods. These innovations offer promising avenues for enhancing crop health and securing the food supply chain against environmental shifts. The integration of these strategies is crucial, demonstrating the potential to transform biosecurity practices and sustain agricultural productivity in the face of changing climatic conditions. This analysis emphasizes the importance of adopting advanced measures to protect crop health and ensure food supply chain resilience, providing valuable insights for stakeholders across the agricultural sector.

Ibrutinib and atrial fibrillation: An in-depth review of clinical implications and management strategies.

Ibrutinib, a targeted therapy for B-cell malignancies, has shown remarkable efficacy in treating various hematologic cancers. However, its clinical use has raised concerns regarding cardiovascular complications, notably atrial fibrillation (AF). This comprehensive review critically evaluates the association between ibrutinib and AF by examining incidence, risk factors, mechanistic links, and management strategies. Through an extensive analysis of original research articles, this review elucidates the complex interplay between ibrutinib's therapeutic benefits and cardiovascular risks. Moreover, it highlights the need for personalized treatment approaches, vigilant monitoring, and interdisciplinary collaboration to optimize patient outcomes and safety in the context of ibrutinib therapy. The review provides a valuable resource for healthcare professionals aiming to navigate the intricacies of ibrutinib's therapeutic landscape while prioritizing patient well-being.

Congenital Anomalies of the Female Genital Tract: A Comprehensive Review.

This comprehensive review provides an in-depth examination of congenital anomalies of the female genital tract, explicitly focusing on the American Society for Reproductive Medicine (ASRM) Müllerian Anomalies Classification. The classification system is crucial for standardizing communication and guiding accurate diagnoses in clinical practice. The review explores the diverse clinical presentations, etiological factors, and diagnostic modalities associated with these anomalies. Management strategies, ranging from conservative approaches to advanced reproductive technologies, are discussed in the context of individualized treatment plans based on the ASRM classification. The psychosocial impact of female genital tract anomalies is thoroughly examined, emphasizing the importance of holistic care and patient-centered approaches. Looking toward the future, the review outlines emerging research areas, including advances in diagnosis techniques, innovative treatment modalities, and genetic studies. It ultimately underscores the need for a comprehensive understanding of physical and psychosocial dimensions, offering insights for healthcare professionals to navigate this complex landscape and improve the lives of affected individuals.

Impact of mechanical ventilation on clinical outcomes in ICU-admitted Alzheimer's disease patients: a retrospective cohort study.

Background: Alzheimer's disease (AD) is increasingly recognized as a pressing global public health issue, demanding urgent development of scientific AD management strategies. In recent years, the proportion of AD patients in Intensive Care Units (ICU) has been on the rise. Simultaneously, the use of mechanical ventilation (MV) is becoming more prevalent among this specific patient group. Considering the pathophysiological characteristics of AD, the application of MV in AD patients may lead to different outcomes. However, due to insufficient research data, the significant impact of MV on the prognosis of AD patients in the ICU remains unclear. Therefore, we conducted this study to comprehensively evaluate the potential influence of MV on the survival rate of AD patients in the ICU. Methods: We obtained data from the MIMIC-IV database for patients diagnosed with AD. Using propensity score matching (PSM), we paired patients who received MV treatment with those who did not receive treatment. Next, we conducted Cox regression analysis to evaluate the association between MV and in-hospital mortality, 7-day mortality, 28-day mortality, 90-day mortality, 4-year mortality, length of hospital stay, and ICU stay. Results: The data analysis involved a cohort of 641 AD patients spanning from 2008 to 2019, inclusive. Following a 1:2 propensity score matching (PSM) procedure, 300 patients were successfully paired, comprising 123 individuals who underwent MV treatment and 177 who did not. MV demonstrated an association with an elevated risk of in-hospital mortality (HR 5.782; 95% CI 2.981-11.216; p < 0.001), 7-day mortality (HR 6.353; 95% CI 3.014-13.392; p < 0.001), 28-day mortality (HR 3.210; 95% CI 1.977-5.210; p < 0.001), 90-day mortality (HR 2.334; 95% CI 1.537-3.544; p < 0.001), and 4-year mortality (HR 1.861; 95% CI 1.370-2.527; p < 0.001). Furthermore, it was associated with a prolonged length of ICU stay [3.6(2.2,5.8) vs. 2.2(1.6,3.7); p = 0.001]. In the subgroup analysis, we further confirmed the robustness of the results obtained from the overall population. Additionally, we observed a significant interaction (p-interaction <0.05) between age, admission type, aspirin use, statin use, and the use of MV. Conclusion: In patients with AD who are receiving treatment in the ICU, the use of MV has been linked to higher short-term, medium-term, and long-term mortality rates, as well as prolong ICU stays. Therefore, it is crucial to break away from conventional thinking and meticulously consider both the medical condition and personal preferences of these vulnerable patients. Personalized treatment decisions, comprehensive communication between healthcare providers and patients, formulation of comprehensive treatment plans, and a focus on collaboration between the ICU and community organizations become imperative.

Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies.

Hepatitis B virus (HBV) reactivation is a clinically significant challenge in disease management. This review explores the immunological mechanisms underlying HBV reactivation, emphasizing disease progression and management. It delves into host immune responses and reactivation's delicate balance, spanning innate and adaptive immunity. Viral factors' disruption of this balance, as are interactions between viral antigens, immune cells, cytokine networks, and immune checkpoint pathways, are examined. Notably, the roles of T cells, natural killer cells, and antigen-presenting cells are discussed, highlighting their influence on disease progression. HBV reactivation's impact on disease severity, hepatic flares, liver fibrosis progression, and hepatocellular carcinoma is detailed. Management strategies, including anti-viral and immunomodulatory approaches, are critically analyzed. The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation. In conclusion, this comprehensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation. With a dedicated focus on understanding its implications for disease progression and the prospects of efficient management strategies, this article contributes significantly to the knowledge base. The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches, ultimately enhancing disease management and elevating patient outcomes. The dynamic landscape of management strategies is critically scrutinized, spanning anti-viral and immunomodulatory approaches. The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.