Portal vein embolization: rationale,outcomes, controversies and future directions

Portal vein embolization (PVE) is now considered the standard of care to improve safety for patients undergoing extensive hepatectomy with an anticipated small future liver remnant (FLR). PVE is used to induce contralateral liver hypertrophy in preparation for major liver resection. Optimal patient selection is essential to maximize the clinical benefits of PVE. Computed tomography volumetry is used to calculate a standardized FLR and determine the need for preoperative PVE. Percutaneous PVE can be performed via the transhepatic ipsilateral or contralateral approaches, depending on operator preference. Several different embolic agents are available to the interventional radiologist, all with similar effectiveness in inducing hypertrophy. When an extended hepatectomy is planned, right PVE should include segment 4, in order to maximize FLR hypertrophy. Multiple studies have demonstrated the beneficial outcomes of PVE in both patients with healthy livers and with underlying liver diseases. Novel improvements to PVE should expand its scope to patients who were previously not candidates for the procedure.     

Geriatric hypertension: aggressive therapy and its physiologic rationale

At any given age, the chance of experiencing a cardiovascular event within the next 5 years increases with the levels of systolic and diastolic BP. Carefully administered antihypertensive therapy has the potential for decreasing the morbidity and mortality of large numbers of elderly patients who have diastolic or mixed hypertension.     

Left ventricular function assessment in cirrhosis: Current methods and future directions

Cirrhotic cardiomyopathy has been defined as a chronic cardiac dysfunction in patients with cirrhosis characterized by impaired contractile responsiveness to stress and/or altered diastolic relaxation with electrophysiological abnormalities in the absence of other known cardiac disease. Non-invasive cardiovascular imaging modalities play a major role in unmasking systolic and diastolic dysfunction in patients with cirrhosis. Echocardiography has been the most commonly used modality for assessing myocardial function in these patients. Conventional echocardiographic indices rely on several assumptions that may limit their applicability in patients with a hyperdynamic circulation. Newer imaging modalities may contribute to a more accurate diagnosis of cardiovascular abnormalities in cirrhotic patients, thereby influencing clinical management. We aimed to review the different non-invasive imaging technologies currently used for assessing left ventricular systolic and diastolic function in cirrhosis, as well as to describe new imaging modalities with potential clinical applicability in the near future.     

Perioperative outcomes and risk assessment in dialysis patients: current knowledge and future directions

Perioperative medicine is rapidly emerging as a key discipline to address the specific needs of high‐risk surgical groups, such as those on chronic dialysis. Crude hospital separation rates for chronic dialysis patients are considerably higher than patients with normal renal function, with up to 15% of admission being related to surgical intervention. Dialysis dependency carries substantial mortality and morbidity risk compared to patients with normal renal function. This group of patients has a high comorbid burden and complex medical need, making accurate perioperative planning essential. Existing perioperative risk assessment tools are unvalidated in chronic dialysis patients. Furthermore, they fail to incorporate important dialysis treatment‐related characteristics that could potentially influence perioperative outcomes. There is a dearth of information on perioperative outcomes of Australasian dialysis patients. Current perioperative outcome estimates stem predominantly from North American literature; however, the generalisability of these findings is limited, as the survival of North American dialysis patients is significantly inferior to their Australasian counterparts and potentially confounds reported perioperative outcomes; let alone regional variation in surgical indication and technique. We propose that data linkage between high‐quality national registries will provide more complete data with more detailed patient and procedural information to allow for more informative analyses to develop and validate dialysis‐specific risk assessment tools.     

Craving research: future directions

Many prospective clinical studies have concluded that craving does not reliably predict relapse and that the concept is of little or no clinical utility. Contrary to earlier more simplistic clinical models of addiction, more recent models do not require that craving be present for relapse to occur. New approaches to study human craving may enhance its predictive validity and yield more knowledge of its nature, course, behavioural sequelae and regulatory function in alcohol/drug consumption. These approaches include empirical research that focuses on: (1) the elucidation of the domains of craving (i.e. subjective experience, physiological responses, behavioural sequelae and their inter-relationships); (2) the temporal dynamics of craving (i.e. its course over minutes or days, as well as its natural history over the course of a drinking career); (3) the factors that may mediate/moderate/determine the development and resolution of craving; (4) studies of the predictive validity of craving measures; and (5) the development of valid methods of measuring the different domains of craving. The conclusions are that future craving research should: (1) incorporate more sophisticated general theories of behaviour (conditioning, cognitive social learning, neurobiological, and genetic); (2) apply more sophisticated and standardized measurement methods and experimental paradigms, including studies in which alcohol is made available to human subjects; and (3) effective development of new pharmacological and behavioural therapies for relapse prevention depend on greater understanding of the nature and measurement of craving.     

Lung cancer: future directions

Increasingly, basic research is being translated into clinical benefits for patients. Recent studies have shed more light on the clinical use of targeted therapies such as tyrosine kinase and angiogenesis inhibitors, and predictive factors for their clinical benefit and their role in different clinical settings are now being elucidated. New insights into the basic biology of lung cancer hold translational promise in risk assessment, early detection, molecular staging, treatment response prediction and novel therapies. New targeted agents directed at apoptotic and developmental pathways have the potential to exploit newly discovered vulnerabilities in the basic machinery of cancer. In addition, exploration of the cancer stem cell phenomenon in lung cancer may generate new approaches to prevent recurrence in surgically respectable lung cancer, and for the long-term control of extensive disease. Molecular profiling may also allow for highly individualized prognostic, predictive and therapeutic treatment plans tailored for each patient based on the molecular diagnostic profile of their tumour. Advances in genetic susceptibility, early detection and individualized therapy based on each tumour's unique biological properties all hold promise for the future management of lung cancer.     

Craving research: future directions

Many prospective clinical studies have concluded that craving does not reliably predict relapse and that the concept is of little or no clinical utility. Contrary to earlier more simplistic clinical models of addiction, more recent models do not require that craving be present for relapse to occur. New approaches to study human craving may enhance its predictive validity and yield more knowledge of its nature, course, behavioural sequelae and regulatory function in alcohol/drug consumption. These approaches include empirical research that focuses on: (1) the elucidation of the domains of craving (i.e. subjective experience, physiological responses, behavioural sequelae and their inter-relationships); (2) the temporal dynamics of craving (i.e. its course over minutes or days, as well as its natural history over the course of a drinking career); (3) the factors that may mediate/moderate/determine the development and resolution of craving; (4) studies of the predictive validity of craving measures; and (5) the development of valid methods of measuring the different domains of craving. The conclusions are that future craving research should: (1) incorporate more sophisticated general theories of behaviour (conditioning, cognitive social learning, neurobiological, and genetic); (2) apply more sophisticated and standardized measurement methods and experimental paradigms, including studies in which alcohol is made available to human subjects; and (3) effective development of new pharmacological and behavioural therapies for relapse prevention depend on greater understanding of the nature and measurement of craving.     

Geriatric assessment for the rheumatologist

The population of industrialized countries is aging rapidly. Rheumatologic disorders are the most common illnesses causing functional disability in the elderly and medications for rheumatologic disorders are among the most frequently prescribed. As the population of patients seen by rheumatologists ages, it is important for the rheumatologist to understand the techniques of geriatric assessment that are useful in understanding and treating this special population. This article reviews practical ways to assess function, cognition, affect, directives, and end-of-life care in elderly populations. The article concludes with a "Top Ten" list of geriatric principles for rheumatology fellows to learn.     

Conclusion and future directions

Bendamustine is a bifunctional mechlorethamine derivative that shares similarities to other alkylators; however, the presence of a benzimidazole ring may confer "nucleoside-like" properties and may allow the stabilization of the molecule leading to longer lasting DNA damage. Though bendamustine has demonstrated promising response rates in preclinical and clinical studies, particularly in follicular lymphoma, chronic lymphocytic leukemia, diffuse B-cell lymphoma, and mantle cell lymphoma, the unique and exact mechanism of action of this agent remains unclear. Several studies have been initiated to address this question, and it is hoped that emerging data will provide the basis for more effective utilization of this interesting drug. Several recent clinical trials have reported impressive results with bendamustine in lymphoid malignancies, and appropriate clinical use of this agent and the rationale behind its use are of growing importance. This review discussed emerging data and aimed to provide clinical updates and scientific rationales that are relevant to practicing clinicians who provide care to patients with lymphoid malignancies, and/or who are interested in understanding the evolving role of bendamustine in this setting.     

COVID-19 therapeutics: Challenges and directions for the future

The emergence of SARS-CoV-2 triggering the COVID-19 pandemic ranks as arguably the greatest medical emergency of the last century. COVID-19 has highlighted health disparities both within and between countries and will leave a lasting impact on global society. Nonetheless, substantial investment in life sciences over recent decades has facilitated a rapid scientific response with innovations in viral characterization, testing, and sequencing. Perhaps most remarkably, this permitted the development of highly effective vaccines, which are being distributed globally at unprecedented speed. In contrast, drug treatments for the established disease have delivered limited benefits so far. Innovative and rapid approaches in the design and execution of large-scale clinical trials and repurposing of existing drugs have saved many lives; however, many more remain at risk. In this review we describe challenges and unmet needs, discuss existing therapeutics, and address future opportunities. Consideration is given to factors that have hindered drug development in order to support planning for the next pandemic challenge and to allow rapid and cost-effective development of new therapeutics with equitable delivery.     

Intermittent preventive therapy for malaria: progress and future directions

PURPOSE OF REVIEW: This review summarizes recent evidence regarding the efficacy of intermittent preventive treatment with focus on infancy (IPTi) and the rationale behind such a control strategy. RECENT FINDINGS: Pooled safety and efficacy analyses of all six trials of IPTi with sulfadoxine-pyrimethamine conducted between 1999 and 2007 have demonstrated a 30% protective efficacy against clinical malaria, a 24% protective efficacy against all-cause hospital admissions, a 37% protective efficacy against malaria-related hospital admissions, and a 15% protective efficacy against anemia, all in the first year of life. Rebound in malaria following discontinuation of the intervention has not been noted in pooled analyses of the IPTi trials. SUMMARY: Given the efficacy, excellent safety and tolerability of the intervention and the fact that it is inexpensive and easily deliverable if linked to the Expanded Programme on Immunization, IPTi-sulfadoxine-pyrimethamine appears to add a valuable tool to the malaria-control armamentarium in endemic areas of Africa. Routine monitoring of sulfadoxine-pyrimethamine efficacy will be required to guide future IPTi programme implementation. Variations of IPTi that target older children may be required for areas of Africa with highly seasonal malaria transmission.     

Geriatric medicine in future

Geriatrics in future will be most concerned with persons aged 80 years or more (very elderly) in Japan. Clinical and pathological features of very elderly patients were reported with comparison to the 65-79 age group. Many very elderly do not show clear-cut clinical signs and symptoms, but have serious underlying diseases. We propose here a concept of "clinical threshold". On evaluating the laboratory data, we must consider the grades of "activity of daily living (ADL)" of the aged patients, because ADL may significantly modify the test results. Furthermore in clinical practice, we should pay attention to both the psychosocial states and physical findings of the patients. "The old age syndrome" proposed by Parker is useful in geriatric medicine. Extensive studies on dementia, especially of Alzheimer's type are required urgently. Molecular biology approaches to this disease have shown great advances in geriatrics. To prevent geriatric disease, well-controlled exercise and diet are important as well as reasonable psychosocial integrity.     

Stents for intracoronary placement: Current status and future directions

The technique of intracoronary stenting has achieved remarkable progress over the last few years. Improved stent deployment techniques and optimization of postprocedural management have dramatically improved the safety of intracoronary stent placement. At present the incidence of early vessel closure after stenting is even lower than that after standard angioplasty and, as most operators no longer prescribe aggressive anticoagulation, bleeding complications are uncommon.Stenting has become an extremely effective treatment for abrupt or threatened vessel closure or for any suboptimal angiographic result during conventional angioplasty. Furthermore, large prospective trials have demonstrated that its efficacy is superior to that of conventional angioplasty for primary restensis prevention in focal lesions of some native coronary arteries. Ongoing trials tend to extrapolate these conclusions to saphenous vein graft lesions.Mechanical support of the vessel wall explains the sustained angiographic benefit observed after stenting. Future developments may include the use of stents as a vehicle for local drug delivery in an attempt to further reduce the incidence of restenosis.In view of these results, coronary stents should be considered a new standard therapeutic modality in interventional cardiology.