Clinical Narrative Review Research Articles

FLT3 and IDH1/2 Inhibitors for Acute Myeloid Leukemia: Focused Clinical Narrative Review of Forthcoming Drugs from an Indian Context

AbstractTherapeutic approaches for acute myeloid leukemia (AML) have witnessed minimal evolution in recent decades, primarily relying on advancements in supportive care and transplantation to drive improvements in overall survival rates. However, treatment with intensive chemotherapy may not be feasible for patients with advanced age or reduced fitness, and outcomes for patients with relapsed/refractory disease continue to be suboptimal. Several agents with a novel mechanism of action have been developed in the past decade and have shown efficacy in patients with both newly diagnosed and relapsed AML. Out of these, several FLT3 (FMS like tyrosine kinase 3) and IDH1/2 (isocitrate dehydrogenase 1/2) inhibitors have received regulatory approval in specific clinical settings and are available for clinical use. This is an actively expanding field with several ongoing clinical trials in advanced phases. We provide a focused narrative review of drugs from these two categories with available clinical data.

Subchondral Insufficiency Fractures of the Knee: A Clinical Narrative Review.

» Subchondral insufficiency fractures of the knee (SIFKs) are subchondral plate fractures with a prevalence of 2% to 4% of all knee injuries.» Magnetic resonance imaging is the gold standard for evaluating SIFK, while plain radiographs have limited the use in the diagnosis of SIFK.» Among patients with SIFK, 50% to 100% have meniscal pathology.» Medical therapies and standard treatments traditionally used in the management of knee osteoarthritis differ from recommended management of SIFK patients.» Randomized controlled trials and cohort studies with long-term follow-up are needed to determine the optimal rehabilitation protocol, interventional therapy, and prognosis of SIFK patients.

The Intraoperative Use of Defensive Antibacterial Coating (DAC®) in the Form of a Gel to Prevent Peri-Implant Infections in Orthopaedic Surgery: A Clinical Narrative Review.

Periprosthetic joint infections (PJIs) in arthroplasty and osteosynthesis-associated infections (OAIs) in reconstructive surgery still represent a challenging complication in orthopaedics and traumatology causing a burden worsening the patient's quality of life, for caregiver and treating physicians, and for healthcare systems. PJIs and OAIs are the result of bacterial adhesion over an implant surface with subsequent biofilm formation. Therefore, the clinical pathological outcome is a difficult-to-eradicate persistent infection. Strategies to treat PJIs and OAIs involve debridement, the replacement of internal fixators or articular prostheses, and intravenous antibiotics. However, long treatments and surgical revision cause discomfort for patients; hence, the prevention of PJIs and OAIs represents a higher priority than treatment. Local antibiotic treatments through coating-release systems are becoming a smart approach to prevent this complication. Hydrophilic coatings, loaded with antibiotics, simultaneously provide a barrier effect against bacterial adhesion and allow for the local delivery of an antibiotic. The intraoperative use of a hyaluronan (HY)-derivative coating in the form of a gel, loaded with antibiotics to prevent PJI, has recently raised interest in orthopaedics. Current evidence supports the use of this coating in the prophylaxis of PJI and IRIs in terms of clinical outcomes and infection reduction. Thus, the purpose of this narrative review is to assess the use of a commercially available HY derivative in the form of a gel, highlighting the characteristics of this biomaterial, which makes it attractive for the management of PJIs and IRIs in orthopaedics and traumatology.

COVID-19 therapy and vaccination: a clinical narrative review.

The SARS-CoV-2 pandemic is the most globally impacting health issue our world has faced over the last century. As of January 7, 2022, around 300 million cases have been reported worldwide, with over 5 million deaths. The SARS-CoV-2 infection causes a hyperactive host immune response leading to an excessive inflammatory reaction with the release of many cytokines - cytokine storm - commonly noticed in acute respiratory distress syndrome, sepsis and fulminant multiorgan failure. Since the beginning of the pandemic, the scientific medical community has worked on therapeutic procedures that interfere with the exaggerated immune response. Thromboembolic complications are widespread in patients who are critically ill with COVID-19. Anticoagulant therapy was initially considered a cornerstone in hospitalized patients and even in the early post-discharge period; however, later trials have aborted the clinical benefits except for suspicion of or confirmed thrombosis. Immunomodulatory therapies are still crucial in moderate to severe COVID-19. Immunomodulator therapies include various medications from steroids to hydroxychloroquine, tocilizumab and Anakinra. Anti-inflammatory agents, vitamin supplements and antimicrobial therapy had initial encouraging evidence, but there are limited data to review. Convalescent plasma, immunoglobulins, eculizumab, neutralizing IgG1 monoclonal antibodies and remdesivir have positively impacted inpatient mortality and hospital length of stay. Eventually, wide population vaccination was proven to be the best tool to overcome the SARS-CoV-2 pandemic and help humanity return to regular life. Many vaccines and various strategies have been used since December 2020. This review discusses how the SARS-CoV-2 pandemic has progressed and surged, and summarizes the safety and efficacy of the most used therapies and vaccines in the light of recent evidence.

Brain Enlarged Perivascular Spaces as Imaging Biomarkers of Cerebrovascular Disease: A Clinical Narrative Review.

Perivascular spaces or Virchow-Robin spaces form pathways along the subarachnoid spaces that facilitate the effective clearance of brain metabolic by-products through intracellular exchange and drainage of cerebrospinal fluid. Best seen on magnetic resonance imaging of the brain, enlarged perivascular spaces (EPVSs) are increasingly recognized as potential imaging biomarkers of neurological conditions. EPVSs are an established subtype of cerebral small-vessel disease; however, their associations with other cerebrovascular disorders are yet to be fully understood. In particular, there has been great interest in the association between the various parameters of EPVSs, such as number, size, and topography, and vascular neurological conditions. Studies have identified cross-sectional and longitudinal relationships between EPVS parameters and vascular events, such as ischemic stroke (both clinical and silent), intracerebral hemorrhage, vascular risk factors, such as age and hypertension, and neurodegenerative processes, such as vascular dementia and Alzheimer disease. However, these studies are limited by heterogeneity of data and the lack of consistent results across studied populations. Existing meta-analyses also fail to provide uniformity of results. We performed a qualitative narrative review with an aim to provide an overview of the associations between EPVSs and cerebrovascular diseases, which may help recognize gaps in our knowledge, inform the design of future studies, and advance the role of EPVSs as imaging biomarkers.

The theatre of depression: a role for physical therapy

ABSTRACT Introduction The world’s population is experiencing an increasing prevalence of depressive disorders. A comprehensive literature review identifies a schism between current medical interventions and the increasing prevalence. Current treatment paradigms warrant analysis. Objective This manuscript theorizes an interdisciplinary team inclusive of physiotherapy as a standard would reverse the increasing prevalence. Physiotherapists’ musculoskeletal expertise and biopsychosocial approach play a valuable role in mental health. Methods A clinical narrative review of depression, including parallels with chronic pain, is provided as a substantive foundation. The review includes challenges in primary care as the gateway to mental health. Depression’s underlying mechanisms, standard interventions, current theories, and future paradigms are explored. Results A theoretical construct was formulated. This construct identified compromised emotion-regulation and self-efficacy as common dysfunctions that enables and perpetuates depression. Physical activity with cognitive reappraisals positively influences these common dysfunctions and improves general intervention outcomes. The psychologically informed physiotherapist is defined. Physiotherapists can provide functional interventions and cognitive reappraisals that address biopsychosocial needs and build resilience. Conclusion Individualized physical and functional activity that facilitate therapeutic alliance, functional improvements, cognitive reappraisals, emotion-regulation and self-efficacy delivered by a physiotherapist provide sustainable behavioral change and completes the interdisciplinary mental health team.

Corrigendum to: "Osteoporosis in Premenopausal Women: A Clinical Narrative Review by the ECTS and the IOF".

Corrigendum to: "Osteoporosis in Premenopausal Women: A Clinical Narrative Review by the ECTS and the IOF".

Osteoporosis in Premenopausal Women: A Clinical Narrative Review by the ECTS and the IOF.

Consensus regarding diagnosis and management of osteoporosis in premenopausal women (PW) is still lacking due to few studies carried out in this population. The European Calcified Tissue Society and the International Osteoporosis Foundation convened a working group to produce an updated review of literature published after 2017 on this topic. Fragility fractures in PW are rare and mostly due to secondary osteoporosis (ie, in presence of an underlying disease such as hormonal, inflammatory, or digestive disorders). In absence of another disorder, low bone mineral density (BMD) together with fragility fractures qualifies as idiopathic osteoporosis. In contrast, low BMD alone does not necessarily represent osteoporosis in absence of bone microarchitectural abnormalities. BMD increases in PW with osteoporosis when the underlying disease is treated. For example, in celiac disease, an increase of 9% in radius trabecular volumetric density was achieved after 1 year of gluten-free diet, while anti-tumor necrosis factor alpha improved BMD in PW with inflammatory bowel diseases. In amenorrhea, including anorexia nervosa, appropriately delivered estrogen replacement therapy can also improve BMD. Alternatively, antiresorptive or anabolic therapy has been shown to improve BMD in a variety of conditions, the range of improvement (3%-16%) depending on skeletal site and the nature of the secondary cause. No studies were powered to demonstrate fracture reduction. The effects of bisphosphonates in childbearing women have been scantly studied and caution is needed. The majority of PW with osteoporosis have an underlying disease. Specific therapy of these diseases, as well as antiresorptive and anabolic drugs, improve BMD, but without evidence of fracture reduction.

Diagnosis and management of hypocalcemia.

The aim of this clinical narrative review is to summarize and critically appraise the literature on the differential diagnosis of hypocalcemia and to provide its correct management. Calcium is essential for muscle contraction and neurotransmitter release, but clinical manifestations of hypocalcaemia (serum calcium level <8 mg/dl; 2.12 mmol/L) may involve almost any organ and system and may range from asymptomatic to life-threating conditions. Disorders causing hypocalcemia can be divided into parathyroid hormone (PTH) and non-PTH mediated. The most frequent cause of hypocalcemia is postsurgical hypoparathyroidism, while a more comprehensive search for other causes is needed for appropriate treatment in the non PTH-mediated forms. Intravenous calcium infusion is essential to raise calcium levels and resolve or minimize symptoms in the setting of acute hypocalcemia. Oral calcium and/or vitamin D supplementation is the most frequently used as treatment of chronic hypocalcemia. In hypoparathyroidism, providing the missing hormone with the use of the recombinant human (rh) PTH(1-84) has been recently approved both by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This new therapy has the advantage of being effective for correcting serum calcium levels and significantly reducing the daily requirements of calcium and active vitamin D supplements. However, due to the high cost, a strict selection of candidates to this therapy is necessary. More challenging is the long-term hypocalcemia treatment, due to its associated complications. The development of long-acting recombinant human PTH will probably modify the management of chronic hypoparathyroidism in the future.

Rare causes of emesis.

Prompt diagnosis in the emergency department in the case of a patient with emesis may be difficult due to the increasing prevalence of diseases which manifest with emesis. Furthermore, in the case of chronic symptomatology, management and therapy are even more complicated. One episode of emesis rarely causes complications, but severe or repetitive episodes of emesis can cause life-threatening complications. For this reason, the diagnosis of the underlying disease which manifests with emesis is mandatory to be established in a short time in order to choose the correct therapeutic option. In order to systemize the process of diagnosis, this clinical narrative review will discuss only rare causes of emesis.

Thrombin generation and bleeding in cardiac surgery: a clinical narrative review

This narrative review discusses the role of thrombin generation in coagulation and bleeding in cardiac surgery, the laboratory methods for clinical detection of impaired thrombin generation, and the available hemostatic interventions that can be used to improve thrombin generation. Coagulopathy after cardiopulmonary bypass (CPB) is associated with excessive blood loss and adverse patient outcomes. Thrombin plays a crucial role in primary hemostasis, and impaired thrombin generation can be an important cause of post-CPB coagulopathy. Existing coagulation assays have significant limitations in assessing thrombin generation, but whole-blood assays designed to measure thrombin generation at the bed-side are under development. Until then, clinicians may need to institute therapy empirically for non-surgical bleeding in the setting of normal coagulation measures. Available therapies for impaired thrombin generation include administration of plasma, prothrombin complex concentrate, and bypassing agents (recombinant activated factor VII and factor eight inhibitor bypassing activity). In vitro experiments have explored the relative potency of these therapies, but clinical studies are lacking. The potential incorporation of thrombin generation assays into clinical practice and treatment algorithms for impaired thrombin generation must await further clinical development.

Neuraxial Regional Anaesthesia in Patients with Active Infection and Sepsis: A Clinical Narrative Review.

Infection is considered to be a relative contraindication for regional anaesthesia. However, there is a paucity of articles addressing the topic of regional anaesthesia in patients with an active infectious process. Recent publications show a low incidence of infection (0.007% to 0.6%) of the central nervous system after neuraxial punctures in patients at risk of, or with ongoing bacteraemia, and a low incidence of infection after performing regional anaesthesia techniques in immunosuppressed patients, or patients with an actual infection. Therefore, some authors conclude that it seems that there is little justification to set strict contraindications regarding this indication and that the risk-benefit ratio should prevail. In addition, a low incidence of meningitis or abscesses after the lumbar puncture has been observed in patients with unsuspected and ongoing bacteraemia, or who were at risk of bacteraemia, when antibiotic therapy has been previously started. For viral infections, regional techniques seem to be safe, being applied in patients with HIV infection. The only established absolute contraindication for any type of regional anaesthesia technique is the infection at the puncture site. Debate persists if a neuraxial anaesthesia technique is to be performed in the course of sepsis with the origin away from the puncture site. In case of thoracic epidural anaesthesia and analgesia, experimental and clinical studies highlight their potential benefits in the systemic inflammatory response syndromes and founded sepsis, both in surgical and non-surgical patients. Finally, the anti-inflammatory and anti-infective effects of local anaesthetics and the basis of excessive inflammatory response are described, as the latter might be involved, in part, in the clinical outcomes.

Strategies for prevention of lower limb post-amputation pain: A clinical narrative review.

Postamputation limb pain or phantom limb pain (PLP) develops due to the complex interplay of peripheral and central sensitization. The pain mechanisms are different during the initial phase following amputation as compared with the chronic PLP. The literature describes extensively about the management of established PLP, which may not be applicable as a preventive strategy for PLP. The novelty of the current narrative review is that it focuses on the preventive strategies of PLP. The institution of preoperative epidural catheter prior to amputation and its continuation in the immediate postoperative period reduced perioperative opioid consumption (Level II). Optimized preoperative epidural or intravenous patient–controlled analgesia starting 48 hours and continuing for 48 hours postoperatively decreased PLP at 6 months (Level II). Preventive role of epidural LA with ketamine (Level II) reduced persistent pain at 1 year and LA with calcitonin decreased PLP at 12 months (Level II). Peripheral nerve catheters have opioid sparing effect in the immediate postoperative period in postamputation patients (Level I), but evidence is low for the prevention of PLP (Level III). Gabapentin did not reduce the incidence or intensity of postamputation pain (Level II). The review in related context mentions evidence regarding therapeutic role of gabapentanoids, peripheral nerve catheters, and psychological therapy in established PLP. In future, randomized controlled trials with long-term follow-up of patients receiving epidural analgesia, perioperative peripheral nerve catheters, oral gabapentanoids, IV ketamine, or mechanism-based modality for prevention of PLP as primary outcome are required.

Management Of Recurrent Thyroglossal Duct Remnants After Sistrunk Procedure: A Clinical Narrative Review Of Surgical Approaches

Management Of Recurrent Thyroglossal Duct Remnants After Sistrunk Procedure: A Clinical Narrative Review Of Surgical Approaches

Dry Needling in the Management of Musculoskeletal Pain

Myofascial pain is a common syndrome seen by family practitioners worldwide. It can affect up to 10% of the adult population and can account for acute and chronic pain complaints. In this clinical narrative review we have attempted to introduce dry needling, a relatively new method for the management of musculoskeletal pain, to the general medical community. Different methods of dry needling, its effectiveness, and physiologic and adverse effects are discussed. Dry needling is a treatment modality that is minimally invasive, cheap, easy to learn with appropriate training, and carries a low risk. Its effectiveness has been confirmed in numerous studies and 2 comprehensive systematic reviews. The deep method of dry needling has been shown to be more effective than the superficial one for the treatment of pain associated with myofascial trigger points. However, over areas with potential risk of significant adverse events, such as lungs and large blood vessels, we suggest using the superficial technique, which has also been shown to be effective, albeit to a lesser extent. Additional studies are needed to evaluate the effectiveness of dry needling. There also is a great need for further investigation into the development of pain at myofascial trigger points.