Current Pharmacological Management Research Articles

Recent advances in the therapeutic management of calcium pyrophosphate deposition disease.

Calcium pyrophosphate deposition (CPPD) disease is a form of crystal-induced arthropathy that arises from the accumulation of calcium pyrophosphate crystals within joints and soft tissues. This process leads to inflammation and damage to the affected joints. It can present asymptomatically or as acute or chronic inflammatory arthritis. Risk factors and comorbidities, including prior joint injury, osteoarthritis, hereditary or familial predisposition, and metabolic diseases, should be evaluated in CPPD cases. The management of CPPD remains a challenge in the sparsity of randomized controlled trials. The lack of such trials makes it difficult to establish evidence-based treatment protocols for CPPD. This review provides an overview of the current pharmacological management of CPPD, focusing on reducing inflammation, alleviating symptoms, and preventing acute flares. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and colchicine are effective in managing acute CPP arthritis. Colchicine may also be used prophylactically to prevent recurrent flares. In cases where other treatments have failed, anakinra, an interleukin-1 receptor antagonist, can be administered to alleviate acute flares. The management of chronic CPP inflammatory arthritis includes NSAIDs and/or colchicine, followed by hydroxychloroquine, low-dose glucocorticoids, and methotrexate, with limited data on efficacy. Tocilizumab can be used in refractory cases. In small studies, synovial destruction using intra-articular injection of yttrium 90 can decrease pain. To date, no disease-modifying therapies exist that reduce articular calcification in CPPD.

Understanding to Concept of Jarajanya Vyadhi (ageing related diseases) w.s.r. to Sandhigatavata (osteo arthritis)

As age advances Vata Dosha increases in an individual. This increasing Vata trigger and accelerates Dhatu Kshaya (depletion of tissues) and Bala Kshaya (diminished the body strength). Hence advancing age makes man prone to many diseases especially degenerative disorders. Asthis (bones) are the main seat of Vata Dosha and Sandhis (joints) is the main seat of Kapha Dosha. Vata Dosha is responsible for different body movements like Prasaarana and Akunchana of Sandhi (flexion and extension of joints), whereas Shleshaka Kapha located in Sandhi (joints) is provides nutrition, protection and to minimize the friction during the movement. Sandhigatavata is Vata pradhana vyadhi. It is quite similar to osteoarthritis, a degenerative joint disease stand in modern medical science. Sandhigatavata is Vata dominating disorder which result in inflammatory and degenerative changes in joints. Osteoarthritis is a disease of musculoskeletal system, affecting the joints mostly in elderly population and in weight bearing joints (particularly knee joint). The current standard modern medical pharmacological management of osteoarthritis includes the administration of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). However, their use neither provides adequate and significant relief in symptoms nor deceleration in disease process. Therefore, Vata shamaka aushadhis along with local application e.g. Abhyanga, different form of Swedana are beneficial. As Sandhigatavata is ageing related heath condition, Rasayana chikitsa can also be helpful in the management of Sandhigatavata (Osteoarthritis). This article enlighten the knowledge about Jarajanya vyadhi especially Sandhigatavata.

The role and application of current pharmacological management in patients with advanced heart failure.

In the last decades, several classifications and definitions have been proposed for advanced heart failure (ADVHF) patients, including clinical, functional, hemodynamic, imaging, and electrocardiographic features. Despite different inclusion criteria, ADVHF is characterized by some common items, such as drug intolerance, low arterial pressure, multiple organ dysfunction, chronic kidney disease, and diuretic use dependency. Additional features include fatigue, hypotension, hyponatremia, and unintentional weight loss associated with a specific laboratory profile reflecting systemic multiorgan dysfunction. Notably, studies evaluating guideline-directed medical therapy recently endorsed by guidelines in stable HF, including the 4 drug classes all together (i.e., betablocker, mineral corticoid antagonist, renin angiotensin inhibitors/neprilysin inhibitors, and sodium glucose transporter inhibitors), remain scarcely analyzed in ADVHF and New York Heart Association (NYHA) Class IV. Additionally, due to the common conditions associated with advanced stages, the balance between drug tolerance and potential benefits of the contemporary use of all agents is questioned. Therefore, less hard endpoints, such as exercise tolerance, quality of life (QoL) and self-competency, are not clearly demonstrated. Specific analyses evaluating outcome and rehospitalization of each drug provided conflicting results and are often limited to subjects with stable conditions and less advanced NYHA class. Current European Society of Cardiology/American Heart Association (ESC/AHA) Guidelines do not indicate the type of treatment, dosage, and administration modalities, and they do not suggest specific indications for ADVHF patients. Due to these concerns, there is an impelling need to understand what drugs may be used as the first line, what management leads to the better outcome, and what is the best treatment algorithm in this setting. In this paper, we summarize the most common pitfalls and limitations for the use of the traditional agents, and we propose a personalized approach aiming at preserve drug tolerance and maintaining adverse event protection and satisfactory QoL.

Osteoporosis: Molecular Pathology, Diagnostics, and Therapeutics.

Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by changes in bone homeostasis, which lead to reduced bone mass, impaired bone quality, and an increased risk of fractures. The pathophysiology of osteoporosis is complex and multifactorial, involving imbalances in hormones, cytokines, and growth factors. Understanding the cellular and molecular mechanisms underlying osteoporosis is essential for appropriate diagnosis and management of the condition. This paper provides a comprehensive review of the normal cellular and molecular mechanisms of bone homeostasis, followed by an in-depth discussion of the proposed pathophysiology of osteoporosis through the osteoimmunological, gut microbiome, and cellular senescence models. Furthermore, the diagnostic tools used to assess osteoporosis, including bone mineral density measurements, biochemical markers of bone turnover, and diagnostic imaging modalities, are also discussed. Finally, both the current pharmacological and non-pharmacological treatment algorithms and management options for osteoporosis, including an exploration of the management of osteoporotic fragility fractures, are highlighted. This review reveals the need for further research to fully elucidate the molecular mechanisms underlying the condition and to develop more effective therapeutic strategies.

Autonomic dysreflexia: Current pharmacologic management.

Autonomic dysreflexia (AD) is a frequent complication of spinal cord injury (SCI), though current clinical practice patterns for medication management of this condition are unknown. Correspondingly, it is unclear if national differences in practice patterns exist. To determine trends in current pharmacologic management of AD throughout the Americas. International survey of current physician practice patterns. Academic medical center. Sixty physicians managing patients with SCI and prescribing medications to manage AD. Not applicable. Presence of a formal pharmacologic AD management protocol, first- and second-line medications, patient characteristics influencing pharmacologic management. The majority of physicians (69%) had a formal AD management protocol for inpatient care, with nitroglycerin ointment (82%) being the most common first-line medication. Strong national differences existed regarding the use of nitroglycerin ointment, with 98% of U.S.-based physicians using this as first-line medication and 0% of physicians in Canada or Latin America using this due to recent lack of medication availability. Only 67% of physicians had a preferred second-line medication, with preferences split between hydralazine (48%) and nifedipine (28%). A systolic blood pressure threshold for pharmacologic management was used by 56% of physicians, wheres 26% considered neurological level of injury in decisions to use medications for AD. Heart rate was used by only 5% of physicians in their decision to manage AD with medications. As of 2023, U.S.-based physicians caring for individuals with SCI largely have formal inpatient protocols in place for medication management of AD, with nearly all relying on nitroglycerin ointment as their first-line medication. In areas outside of the United States where nitroglycerin ointment is unavailable, pharmacologic practice patterns significantly differ.

The efficacy of exogenous melatonin supplement in ameliorating irritable bowel syndrome severity: A meta-analysis of randomized controlled trials

Irritable bowel syndrome (IBS) was found in 11% of the general population worldwide. The current pharmacologic management of IBS was unsatisfactory, and it was accompanied by a number of adverse events. Melatonin was found to play an important role in gastrointestinal smooth muscle motility. Dysregulation of endogenous melatonin secretion has been found in IBS patients. Exogenous melatonin supplement has become one alternative treatment for IBS, but the evidence is inconclusive. The current meta-analysis sought to determine the efficacy of exogenous melatonin supplement in improving IBS severity in IBS patients. We included randomized controlled trials (RCTs) that investigated the efficacy of exogenous melatonin supplement in ameliorating IBS severity in IBS patients. This meta-analysis was conducted using a random effects model. The primary target outcomes were changes in IBS severity associated with melatonin or placebo. This meta-analysis of 4 RCTs and 115 participants revealed that exogenous melatonin supplement was associated with significantly better improvement in overall IBS severity than placebo (k=4, Hedges' g=0.746, 95% confidence intervals=0.401-1.091, p<0.001). The subgroup without concurrent medication had the same result (p<0.001). In addition, exogenous melatonin supplement was also associated with significantly better improvement in IBS pain severity (p<0.001) and quality of life (p=0.007) than placebo, but not in abdominal distension (p=0.111) or sleep quality (p=0.142). Finally, melatonin was associated with similar safety profiles with placebo. This meta-analysis provides evidence for the use of exogenous melatonin in IBS patients to ameliorate overall IBS severity, IBS pain severity, and quality of life. PROSPERO CRD42021269451.

Consensus statement on the current pharmacological prevention and management of heart failure.

Introduction: This consensus statement of Australian clinicians provides new recommendations for the pharmacological management of heart failure based on studies reported since the publication of the 2018 Australian heart failure guidelines. Main recommendations: ▪Use of sodium–glucose cotransporter 2 (SGLT2) inhibitors to prevent hospitalisation for heart failure in type 2 diabetes mellitus can be extended to patients with multiple cardiovascular risk factors, albuminuric chronic kidney disease, or atherosclerotic cardiovascular disease.▪New evidence supports the use of a mineralocorticoid receptor antagonist (finerenone) to prevent heart failure in type 2 diabetes mellitus associated with albuminuric chronic kidney disease.▪In addition to renin angiotensin system inhibitors (angiotensin receptor neprilysin inhibitor preferred), beta blockers and mineralocorticoid receptor antagonists, an SGLT2 inhibitor (dapagliflozin or empagliflozin) is recommended in all patients with heart failure with reduced left ventricular ejection fraction (LVEF ≤ 40%) (HFrEF). Lower quality evidence supports these therapies in patients with heart failure with mildly reduced LVEF (41‐49%) (HFmrEF).▪A soluble guanylate cyclase stimulator (vericiguat), selective cardiac myosin activator (omecamtiv mecarbil) and, if iron deficient, intravenous iron (ferric carboxymaltose) provide additional benefits in persistent HFrEF.▪An SGLT2 inhibitor (empagliflozin) should be considered in patients with heart failure with preserved LVEF (≥ 50%) (HFpEF). Key changes in management from this statement: This document broadens the scope of angiotensin receptor neprilysin inhibitor use in patients with HFrEF and HFmrEF. SGLT2 inhibitor use expands to become a cornerstone therapy in HFrEF, with increasing evidence to support its use in HFmrEF and HFpEF.

Current Knowledge and Future Directions in Huntington’s Disease

Introduction: Huntington's Disease (HD) is a hereditary, neurodegenerative disorder due to abnormal repeats of the CAG triplet in the IT-15 gene. It is characterized by a triad of progressive motor, psychiatric and cognitive symptoms, resulting from striatal neuronal loss. The impact of HD in Latin America is evidenced by the prevalence rates in Maracaibo (Venezuela) and Juan de Acosta (Colombia), which are the highest recorded in the world. This contrasts with the social abandonment and the scarce intervention of local governments.&#x0D; Aim: Provide an approach to the most relevant aspects of HD from its pathogenesis and associated genetic polymorphisms, to the current treatment options.&#x0D; Methodology: A literature review was performed of the state of the art of prognosis and treatment strategies in HD, including the identification of different polymorphic markers in the genes coding for UCHL1, HIP1, PGC1α, GRIK2, TBP, BDNF, among others, and its associations in the evolution of the disease in the presence of abnormal CAG repeats.&#x0D; Conclusion: Even though in the last decades many researchers have focused on the development of curative treatment, there is no effective therapeutic target to prevent the clinical onset of the disease or to delay its progression. Instead, current pharmacological management is palliative, the evidence to generalize the surgical approaches is insufficient. Newly, the fetal neural cell transplantation into the striatum is offered as the surgical option that provides hope for the development of a true disease-modifying treatment.

Current Knowledge and Future Directions in Huntington’s Disease

Introduction: Huntington's Disease (HD) is a hereditary, neurodegenerative disorder due to abnormal repeats of the CAG triplet in the IT-15 gene. It is characterized by a triad of progressive motor, psychiatric and cognitive symptoms, resulting from striatal neuronal loss. The impact of HD in Latin America is evidenced by the prevalence rates in Maracaibo (Venezuela) and Juan de Acosta (Colombia), which are the highest recorded in the world. This contrasts with the social abandonment and the scarce intervention of local governments.&#x0D; Aim: Provide an approach to the most relevant aspects of HD from its pathogenesis and associated genetic polymorphisms, to the current treatment options.&#x0D; Methodology: A literature review was performed of the state of the art of prognosis and treatment strategies in HD, including the identification of different polymorphic markers in the genes coding for UCHL1, HIP1, PGC1α, GRIK2, TBP, BDNF, among others, and its associations in the evolution of the disease in the presence of abnormal CAG repeats.&#x0D; Conclusion: Even though in the last decades many researchers have focused on the development of curative treatment, there is no effective therapeutic target to prevent the clinical onset of the disease or to delay its progression. Instead, current pharmacological management is palliative, the evidence to generalize the surgical approaches is insufficient. Newly, the fetal neural cell transplantation into the striatum is offered as the surgical option that provides hope for the development of a true disease-modifying treatment.

Localizing the expression of Piezo2 in healthy and diseased lung tissue

Intractable air hunger remains one of the most impactful symptoms of chronic cardiopulmonary disease and current pharmacological management remains limited. However, an endogenous mechanism for air hunger relief exists. Pulmonary stretch receptors (PSRs) responding to lung inflation reduce the brainstem drive to breathe and mitigate air hunger. Harnessing this mechanism could form the basis of a novel therapy. Recent animal studies suggest Piezo2, a mechanically‐gated cation channel, causes PSR depolarization when airway smooth muscle is stretched during inflation. We have assessed whether Piezo2 is associated with PSRs in healthy and diseased human airways to determine whether Piezo2 is a potential pharmaceutical target.MethodsHuman lung biopsies from NIH Lung Tissue Research Consortium were used for identification of Piezo2 receptors in emphysema, fibrosis, bronchiolitis, and normal lung tissue. Localization of Piezo2 was determined with immunofluorescent staining and imaged with confocal microscopy (Zeiss LSM880). As PSR fiber endings are associated with airway smooth muscle, co‐staining for Smooth Muscle Antibody (SMA) and Calcitonin Gene‐Related Peptide (CGRP) was performed to determine whether Piezo2 is associated with PSR.Summary of resultsPiezo2 is associated with airway smooth muscle (as evidenced by SMA, figure 1) and neuroepithelial bodies in normal human lung tissue (evidenced by cGRP, figure 2) and expression persisted in all disease states tested.ConclusionsPiezo2 location is consistent with that of PSR in human lungs, making it a candidate for the mechanoreceptive transducer of human PSRs as has been demonstrated in animal studies. Expression persists in disease, making Piezo2 a potential therapeutic target, but it is still yet to be determined if Piezo2 is more significantly associated with airway or vascular smooth muscle in different disease states.

Real-World Eculizumab Dosing Patterns Among Patients with Paroxysmal Nocturnal Hemoglobinuria in a US Population.

PurposeCurrent pharmacologic management of paroxysmal nocturnal hemoglobinuria (PNH) consists of C5 inhibitors, eculizumab and ravulizumab; however, because patients experience incomplete symptom control, off-label doses may be utilized. We conducted a retrospective, longitudinal cohort study of provider-based claims data to assess the real-world eculizumab dosing patterns in PNH patients.Patients and MethodsPatients were ≥12 years, received ≥2 eculizumab infusions between January 1, 2015 and September 30, 2019, and had ≥3 months of continuous clinical activity prior to index. The index date was the first claim for eculizumab. Patients with ≥1 diagnosis of another indication for eculizumab were excluded. Treatment patterns including the proportion with high, label-recommended, and low dosages during induction (first 28 days) and maintenance (beginning day 29) phases were described. The proportion and time-to-first dose escalation, defined as an increase in dose or frequency of infusion, were assessed among a subset of patients (ie, escalation analysis cohort).ResultsA total of 707 patients were examined. Mean (standard deviation [SD]) starting dose was 862mg (412mg) and was higher than label-recommended 600mg for 64% of the patients. Mean (SD) dose per infusion was 859mg (391mg) during the induction phase; average dose was higher than label-recommended 600mg for 68%. Mean (SD) dose per infusion during the maintenance phase was 1005mg (335mg); average dose was higher than label-recommended 900mg for 43%. Dose escalation occurred in 40/121 escalation analysis cohort patients. Median time-to-first dose escalation was ~12 months.ConclusionResults suggest that deviations from label-recommended dosing patterns were common. Future budget impact assessments of eculizumab should account for real-world dosing patterns to comprehensively assess costs and benefits.

Commonly Prescribed Anticoagulants Exert Anticancer Effects in Oral Squamous Cell Carcinoma Cells In Vitro.

Simple SummaryOral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide with 840,000 new cases and 420,000 deaths in 2020. Anticoagulants are widely prescribed medications routinely administered to help prevent blood clots. Despite the great relevance of these two topics, there is complete lack of knowledge regarding the potential effects that these drugs could exert on oral cancer patients. In this in vitro study, we comprehensively investigated the effect of anticoagulants on OSCC activity. This includes the effect of these drugs on cancer cell ability to survive, migrate to colonise distant sites, and resist treatment with conventional chemotherapy. We have demonstrated for the first time that various anticoagulants have anticancer effects on OSCC. Moreover, some of the anticoagulants tested were able to reduce the migratory ability of cancer cells. Finally, the great majority of anticoagulants studied reduced the effectiveness of the tested chemotherapeutic agent, allowing an increase in cancer cell proliferation. Our results highlight the need for urgent further research in the field, to improve the anticoagulant strategies in patients with oral cancer, and in turn their prognosis.Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. With anticoagulant usage on the rise, it is important to elucidate their potential effects on tumour biology and interactions with chemotherapeutics. The aim of the present study was to investigate the effects of anticoagulants on OSCC cell lines and their interactions with the drug 5-fluorouracil (5-FU). Cell proliferation was assessed using an MTS in vitro assay in two human OSCC cell lines (H357/H400) and in normal oral keratinocytes (OKF6) treated with the 5-FU (0.2/1/5/10 μg/mL), conventional anticoagulants warfarin (1/5/10/20 μM) and heparin (5/20/80 U), as well as four new oral anticoagulants, dabigatran (5/10/20 μM), rivaroxaban (5/10/20 μM), apixaban (0.1/1/5 μg/mL), and edoxaban (5/10/20 μM). Cell migration was assessed at 3 h intervals up to18 h using a wound healing assay. Our results clearly demonstrate, for the first time, that commonly prescribed anticoagulants exert in vitro antiproliferative effects on OSCC cells. Furthermore, treatment with some anticoagulants reduced the migration of OSCC cell lines. Nevertheless, most of the anticoagulants tested reduced the effectiveness of the chemotherapeutic agent tested, 5-FU, highlighting potential flaws in the current pharmacological management of these patients. Our findings showed the need for the immediate translation of this research to preclinical animal models.

Breakthrough Cancer Pain: The Current Pharmacological Management

Background: Breakthrough pain (BTP) is a transient increase in pain that occurs on a background of stable pain. It contributes substantially to the suffering experienced by most cancer patients. The pharmacologic options for management of BTP have been expanded considerably in the past decade. Opioids remain the most effective pharmaceuticals used for the BTP case. In this systematic review we attempted to provide the currently available clinical data about pharmacological treatment for breakthrough cancer pain.Objective: To evaluate the efficacy of pharmacological treatments for Breakthrough painMethods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed for the last ten years (from September 2010 to September 2020. Further potentially relevant studies were identified from reference lists of studies marked for inclusion and relevant reviews. Two review authors independently assessed trial quality and extracted data. We screened the search results and included studies if they met the selection criteria.Result: We screened 205 publications of which 14 met the inclusion criteria. In total, we analysed data from 2129 participants. Overall, participant with BTP were treated with short acting opioid. Literature searching did not find any published evidence of non opioid drug to treat the BTP. Most adverse effects of the investigated drugs seemed to be moderate.Conclusion: The findings of this review suggest that rapid onset opioids play significant role for BTP. Future studies may be conducted to explore the efficacy and safety profiles each regimen for patients with certain categories of cancer.

The Molecular Basis and Pathophysiology of Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.

Novel treatments for myelofibrosis: beyond JAK inhibitors.

Myelofibrosis is a chronic hematologic malignancy characterized by constitutional symptoms, bone marrow fibrosis, extramedullary hematopoiesis resulting in splenomegaly and a propensity toward leukemic progression. Given the central role of the JAK-STAT pathway in the pathobiology of myelofibrosis, JAK inhibitors are the mainstay of current pharmacologic management. Although these therapies have produced meaningful improvements in splenomegaly and symptom burden, JAK inhibitors do not significantly impact disease progression. In addition, many patients are ineligible because of disease-related cytopenias, which are exacerbated by JAK inhibitors. Therefore, there is a continued effort to identify targets outside the JAK-STAT pathway. In this review, we discuss novel therapies in development for myelofibrosis. We focus on the preclinical rationale, efficacy and safety data for non-JAK inhibitor therapies that have published or presented clinical data. Specifically, we discuss agents that target epigenetic modification (pelabresib, bomedemstat), apoptosis (navitoclax, navtemdalin), signaling pathways (parsaclisib), bone marrow fibrosis (AVID200, PRM-151), in addition to other targets including telomerase (imetelstat), selective inhibitor of nuclear transport (selinexor), CD123 (tagraxofusp) and erythroid maturation (luspatercept). We end by providing commentary on the ongoing and future therapeutic development in myelofibrosis.

Postoperative pain after total joint arthroplasty: Pathophysiology and current pharmacological pain management

Postoperative pain after total joint arthroplasty: Pathophysiology and current pharmacological pain management

Targeting miRNA by Natural Products: A Novel Therapeutic Approach for Nonalcoholic Fatty Liver.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) as multifactorial chronic liver disease and the lack of a specific treatment have begun a new era in its treatment using gene expression changes and microRNAs. This study aimed to investigate the potential therapeutic effects of natural compounds in NAFLD by regulating miRNA expression. MicroRNAs play essential roles in regulating the cell's biological processes, such as apoptosis, migration, lipid metabolism, insulin resistance, and adipocyte differentiation, by controlling the posttranscriptional gene expression level. The impact of current NAFLD pharmacological management, including drug and biological therapies, is uncertain. In this context, various dietary fruits or medicinal herbal sources have received worldwide attention versus NAFLD development. Natural ingredients such as berberine, lychee pulp, grape seed, and rosemary possess protective and therapeutic effects against NAFLD by modifying the gene's expression and noncoding RNAs, especially miRNAs.

Current Pharmacological Management of Aortic Aneurysm.

Aortic aneurysm (AA) remains one of the primary causes of death worldwide. Of the major treatments, prophylactic operative repair is used for AA to avoid potential aortic dissection or rupture. To halt the development of AA and alleviate its progression into aortic dissection, pharmacological treatment has been investigated for years. Currently, β-adrenergic blocking agents, losartan, irbesartan, angiotensin-converting-enzyme inhibitors, statins, antiplatelet agents, doxycycline, and metformin have been investigated as potential candidates for preventing AA progression. However, the paradox between preclinical successes and clinical failures still exists, with no medical therapy currently available for ideally negating the disease progression. This review describes the current drugs used for pharmacological management of AA and their individual potential mechanisms. Preclinical models for drug screening and evaluation are also discussed to gain a better understanding of the underlying pathophysiology and ultimately find new therapeutic targets for AA.

Progression in the Management of Non-Idiopathic Pulmonary Fibrosis Interstitial Lung Diseases, Where Are We Now and Where We Would Like to Be.

A significant proportion of patients with interstitial lung disease (ILD) may develop a progressive fibrosing phenotype characterized by worsening of symptoms and pulmonary function, progressive fibrosis on chest computed tomography and increased mortality. The clinical course in these patients mimics the relentless progressiveness of idiopathic pulmonary fibrosis (IPF). Common pathophysiological mechanisms such as a shared genetic susceptibility and a common downstream pathway—self-sustaining fibroproliferation—support the concept of a progressive fibrosing phenotype, which is applicable to a broad range of non-IPF ILDs. While antifibrotic drugs became the standard of care in IPF, immunosuppressive agents are still the mainstay of treatment in non-IPF fibrosing ILD (F-ILD). However, recently, randomized placebo-controlled trials have demonstrated the efficacy and safety of antifibrotic treatment in systemic sclerosis-associated F-ILD and a broad range of F-ILDs with a progressive phenotype. This review summarizes the current pharmacological management and highlights the unmet needs in patients with non-IPF ILD.

Current Pharmacological Intervention and Medical Management for Diabetic Kidney Transplant Recipients.

Hyperglycemia after kidney transplantation is common in both diabetic and non-diabetic patients. Both pretransplant and post-transplant diabetes mellitus are associated with increased kidney allograft failure and mortality. Glucose management may be challenging for kidney transplant recipients. The pathophysiology and pattern of hyperglycemia in patients following kidney transplantation is different from those with type 2 diabetes mellitus. In patients with pre-existing and post-transplant diabetes mellitus, there is limited data on the management of hyperglycemia after kidney transplantation. The following article discusses the nomenclature and diagnosis of pre- and post-transplant diabetes mellitus, the impact of transplant-related hyperglycemia on patient and kidney allograft outcomes, risk factors and potential pathogenic mechanisms of hyperglycemia after kidney transplantation, glucose management before and after transplantation, and modalities for prevention of post-transplant diabetes mellitus.