Annual review of medicine最新文献

Resistant hypertension (RH) is a severe form of hypertension associated with increased cardiovascular risk. Although true RH affects less than 10% of the patients receiving antihypertensive therapy, the absolute number is high and continues to increase. The workup of these patients requires screening for secondary hypertension and pseudoresistance, including poor adherence to prescribed medicines and the white-coat phenomenon. The treatment of RH consists of lifestyle modifications and pharmacological therapies. Lifestyle modifications include dietary adjustments, weight loss, physical activity, and limiting alcohol consumption; pharmacological therapies include diuretics, mineralocorticoid receptor antagonists, beta blockers, angiotensin receptor-neprilysin inhibitors, and others. Over the last 15 years, interventional approaches have emerged as adjunct treatment options; we highlight catheter-based renal denervation. This review summarizes the rationales and latest clinical evidence and, based thereon, proposes an updated algorithm for the management of RH.

When the US Food and Drug Administration used the accelerated approval process to authorize the use of the antiamyloid drug aducanumab to treat Alzheimer's disease (AD), many people hoped this signaled a new era of disease-modifying treatment. But 2 years later, aducanumab's failure to launch provides a cautionary tale about the complexities of dementia and the need for a thorough and transparent review of the role that regulatory agencies and various stakeholders play in approving AD drugs. We highlight the events leading to aducanumab's controversial approval and discuss some of the key lessons learned from the drug's failure to deliver the hoped-for benefits. These lessons include the inherent limitations of antiamyloid strategies for a complex disease in which amyloid is only one of several pathological processes, the need for clinical trials that better reflect the diversity of communities affected by AD, the potential pitfalls of futility analyses in clinical trials, the need for greater transparency and other modifications to the approval process, and the dementia field's unreadiness to move from the highly controlled environment of clinical trials to the widespread and chronic use of resource-intensive, disease-modifying drugs in real-world treatment scenarios. People with dementia desperately need effective therapies. We hope that the aducanumab story will inspire changes to the approval process-changes that restore public trust and improve future efforts to deliver disease-modifying therapies to the clinic.

Major depressive disorder (MDD) is a leading cause of suicide in the world. Monoamine-based antidepressant drugs are a primary line of treatment for this mental disorder, although the delayed response and incomplete efficacy in some patients highlight the need for improved therapeutic approaches. Over the past two decades, ketamine has shown rapid onset with sustained (up to several days) antidepressant effects in patients whose MDD has not responded to conventional antidepressant drugs. Recent preclinical studies have started to elucidate the underlying mechanisms of ketamine's antidepressant properties. Herein, we describe and compare recent clinical and preclinical findings to provide a broad perspective of the relevant mechanisms for the antidepressant action of ketamine.

Antibody-drug conjugates (ADCs) have become the cornerstone of effective therapeutics in solid and hematological malignancies by harnessing potent cytotoxic payloads with targeted tumoricidal delivery. Since the monumental shift occurred with HER2-targeted ADCs, the discovery of the TROP2 antigen has revolutionized the landscape of ADC development. Moving beyond the traditional ADC design, multiple novel ADCs have successfully shaped and improved survival outcomes in patients with various tumor histologies. Here we review and contrast the clinical impact of the well-known TROP2 ADCs currently in clinical use. We also shed light on upcoming investigational TROP2 ADCs showing promise with novel ADC platforms.

Older adults commonly end up on many medications. Deprescribing is an important part of individualizing care for older adults. It is an opportunity to discuss treatment options and revisit medications that may not have been reassessed in many years. A large evidence base exists in the field, suggesting that deprescribing is feasible and safe, though questions remain about the potential clinical benefits. Deprescribing research faces a myriad of challenges, such as identifying and employing the optimal outcome measures. Further, there is uncertainty about which deprescribing approaches are likely to be most effective and in what contexts. Evidence on barriers and facilitators to deprescribing has underscored how deprescribing in routine clinical practice can be complex and challenging. Thus, finding practical, sustainable ways to implement deprescribing is a priority for future research in the field.

Multiple myeloma is a cancer of bone marrow plasma cells that represents approximately 10% of hematologic malignancies. Though it is typically incurable, a remarkable suite of new therapies developed over the last 25 years has enabled durable disease control in most patients. This article briefly introduces the clinical features of multiple myeloma and aspects of multiple myeloma biology that modern therapies exploit. Key current and emerging treatment modalities are then reviewed, including cereblon-modulating agents, proteasome inhibitors, monoclonal antibodies, other molecularly targeted therapies (selinexor, venetoclax), chimeric antigen receptor T cells, T cell-engaging bispecific antibodies, and antibody-drug conjugates. For each modality, mechanism of action and clinical considerations are discussed. These therapies are combined and sequenced in modern treatment pathways, discussed at the conclusion of the article, which have led to substantial improvements in outcomes for multiple myeloma patients in recent years.

Recent advances in the treatment of tuberculosis (TB) have led to improvements unprecedented in our lifetime. Decades of research in developing new drugs, especially for multidrug-resistant TB, have created not only multiple new antituberculous agents but also a new approach to development and treatment, with a focus on maximizing the benefit to the individual patient. Prevention of TB disease has also been improved and recognized as a critical component of global TB control. While the momentum is positive, it will take continued investment at all levels, especially training of new dedicated TB researchers and advocates around the world, to maintain this progress.

Prostate-specific membrane antigen (PSMA) as a transmembrane protein is overexpressed by prostate cancer (PC) cells and is accessible for binding antibodies or low-molecular-weight radioligands due to its extracellular portion. Successful targeting of PSMA began with the development of humanized J591 antibody. Due to their faster clearance compared to antibodies, small-molecule radioligands for targeted imaging and therapy of PC have been favored in recent development efforts. PSMA positron emission tomography (PET) imaging has higher diagnostic performance than conventional imaging for initial staging of high-risk PC and biochemical recurrence detection/localization. However, it remains to be demonstrated how to integrate PSMA PET imaging for therapy response assessment and as an outcome endpoint measure in clinical trials. With the recent approval of ¹⁷⁷Lu-PSMA-617 by the US Food and Drug Administration for metastatic castration-resistant PC progressing after chemotherapy, the high value of PSMA-targeted therapy was confirmed. Compared to standard of care, PSMA-based radioligand therapy led to a better outcome and a higher quality of life. This review, focusing on the advanced PC setting, provides an overview of different approved and nonapproved PSMA-targeted imaging and therapeutic modalities and discusses the future of PSMA-targeted theranostics, also with an outlook on non-radiopharmaceutical-based PSMA-targeted therapies.

The COVID-19 pandemic led to disruption of health services around the world, including cancer services. We carried out a narrative review of the effect of the pandemic on cancer prevention services, including screening. Services were severely affected in the early months of the pandemic, and in some areas are still recovering. Large numbers of additional cancers or additional late-stage cancers have been predicted to arise over the coming years as a result of this disruption. To minimize the effects on cancer outcomes, it is necessary to return as quickly as possible to prepandemic levels of screening and prevention activity or indeed to exceed these levels. The recovery of services should address health inequalities.

The MELD (model for end-stage liver disease) 3.0 score was developed to replace the MELD-Na score that is currently used to prioritize liver allocation for cirrhotic patients awaiting liver transplantation in the United States. The MELD 3.0 calculator includes new inputs from patient sex and serum albumin levels and has new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is expected that use of MELD 3.0 scores will reduce overall waitlist mortality modestly and improve access for female liver transplant candidates. The utility of MELD 3.0 and PELD_cre (pediatric end-stage liver disease, creatinine) scores for risk stratification in cirrhotic patients undergoing major abdominal surgery, placement of a transjugular intrahepatic portosystemic shunt, and other interventions requires further study. This article reviews the background of the MELD score and the rationale to create MELD 3.0 as well as potential implications of using this newer risk stratification tool in clinical practice.