Older Agents Research Articles

Advantages of Newer Inhalational Anesthetic Agents over the Older Agents

The objective of anesthesia is to facilitate surgery at minimal risk to the patient and to ensure optimal recovery following the procedure. Sevoflurane is a potent nonexplosive newer inhalational anesthetic agent that has several advantages. Various side effects like arrhythmia, hepatotoxicity, and delayed recovery limit the use of older agent halothane in many western countries. However, we do not have such studies done in our country. This prospective study was carried out in the Department of Anesthesia, Analgesia and Intensive Care Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from September 2009 to June 2011, to analyze the advantages of newer inhalational agents over the older agents. A total of 60 patients were recruited in this study: 30 in Sevoflurane and 30 in Halothane group. We assessed hemodynamics and recovery after sevoflurane and halothane anesthesia. The mean arterial pressure (MAP) and the heart rate (HR) at 15 minutes interval were similar in both groups except at 75 minutes, when both MAP and HR were significantly higher in the halothane group as p=0.003 and p=0.001 respectively. Emergence time was 10.85 min. in the sevoflurane group and 15.13 min. in the halothane group (p<0.001). The mean BAMSE score and time to complete (TMT-A) at half an hour after recovery was significantly higher (29.3) (p=0.014) and significantly less (40.9 sec.) (p<0.001) in sevoflurane group. Our data suggests that sevoflurane is a better anesthetic agent than halothane in terms of balanced hemodynamics, shorter emergence time and early cognitive recovery. CBMJ 2024 July: vol. 13 no. 02 P: 227-234

Prevalence of Diabetes Mellitus in People Living With HIV in Dammam, Saudi Arabia.

Backgrounds The incidence of diabetes mellitus (DM) in people living with human immunodeficiency virus (HIV) receiving highly active antiretroviral therapy (HAART) is thought to be higher than that in noninfected people. The aim of this study was to investigate the prevalence of DM among people living with HIV in Dammam, Saudi Arabia (SA). Methods This was a cross-sectional study that included adult patients with HIV who were followed at Dammam Medical Complex. The electronic medical records of the patients were reviewed for their demographic data, comorbid conditions, and HIV history (e.g., duration and medications). The patients were categorized based on their glycated hemoglobin (A1C) levels into nondiabetic patients (A1C < 5.7%), prediabetic patients (A1C between 5.7% and 6.4%), and diabetic patients (A1C ≥ 6.5). Results A total of 769 HIV patients were assessed. The A1C of 325 patients could not be retrieved. The remaining 444 patients were included in the analysis. These consisted of 71 female patients (15.99%) and 373 male patients (84.01%). The average age of the patients was 38.62±11.33 years. Their duration for living with HIV was on average 3.76±3.15 years. The cohort consisted of 290 nondiabetic patients (65.32%), 107 prediabetic patients (24.1%), and 47 diabetic patients (10.59%). The nondiabetic patients were generally younger than the prediabetic patients (35.97 vs 40.72 years on average, P value < 0.001). They were infected with HIV for shorter durations (3.45 vs 4.19 years on average, P value < 0.05) with a higher percentage of patients receiving antiretroviral therapy (97.93% vs 84.11%, P value < 0.001). Similarly, the nondiabetic patients were generally younger than the diabetic patients (35.97 vs 50.19 years on average, P value < 0.001). They were also infected with HIV for shorter durations (3.45 vs 4.65 years on average, P value < 0.05) with, also, a higher percentage of patients receiving antiretroviral therapy (97.93% vs 89.36%, P value < 0.01). Conclusions The prevalence of DM among people living with HIV in Dammam, SA, was high with DM remaining highly underdiagnosed in this population. However, the prevalence of DM in this study involving mostly HIV patients treated with newer HAART agents was lower than what was reported in multiple previous studies that included patients using older agents.

In vitro development of resistance against antipseudomonal agents: comparison of novel β-lactam/β-lactamase inhibitor combinations and other β-lactam agents.

We subjected seven P. aeruginosa isolates to a 10-day serial passaging against five antipseudomonal agents to evaluate resistance levels post-exposure and putative resistance mechanisms in terminal mutants were analyzed by whole-genome sequencing analysis. Meropenem (mean, 38-fold increase), cefepime (14.4-fold), and piperacillin-tazobactam (52.9-fold) terminal mutants displayed high minimum inhibitory concentration (MIC) values compared to those obtained after exposure to ceftolozane-tazobactam (11.4-fold) and ceftazidime-avibactam (5.7-fold). Fewer isolates developed elevated MIC values for other β-lactams and agents belonging to other classes when exposed to meropenem in comparison to other agents. Alterations in nalC and nalD, involved in the upregulation of the efflux pump system MexAB-OprM, were common and observed more frequently in isolates exposed to ceftazidime-avibactam and meropenem. These alterations, along with ones in mexR and amrR, provided resistance to most β-lactams and levofloxacin but not imipenem. The second most common gene altered was mpl, which is involved in the recycling of the cell wall peptidoglycan. These alterations were mainly noted in isolates exposed to ceftolozane-tazobactam and piperacillin-tazobactam but also in one cefepime-exposed isolate. Alterations in other genes known to be involved in β-lactam resistance (ftsI, oprD, phoP, pepA, and cplA) and multiple genes involved in lipopolysaccharide biosynthesis were also present. The data generated here suggest that there is a difference in the mechanisms selected for high-level resistance between newer β-lactam/β-lactamase inhibitor combinations and older agents. Nevertheless, the isolates exposed to all agents displayed elevated MIC values for other β-lactams (except imipenem) and quinolones tested mainly due to alterations in the MexAB-OprM regulators that extrude these agents.

Preclinical and clinical evaluation of the Janus Kinase inhibitor ruxolitinib in multiple myeloma.

Multiple myeloma (MM) is the most common primary malignancy of the bone marrow. No established curative treatment is currently available for patients diagnosed with MM. In recent years, new and more effective drugs have become available for the treatment of this B-cell malignancy. These new drugs have often been evaluated together and in combination with older agents. However, even these novel combinations eventually become ineffective; and, thus, novel therapeutic approaches are necessary to help overcome resistance to these treatments. Recently, the Janus Kinase (JAK) family of tyrosine kinases, specifically JAK1 and JAK2, has been shown to have a role in the pathogenesis of MM. Preclinical studies have demonstrated a role for JAK signaling in direct and indirect growth of MM and downregulation of anti-tumor immune responses in these patients. Also, inhibition of JAK proteins enhances the anti-MM effects of other drugs used to treat MM. These findings have been confirmed in clinical studies which have further demonstrated the safety and efficacy of JAK inhibition as a means to overcome resistance to currently available anti-MM therapies. Additional studies will provide further support for this promising new therapeutic approach for treating patients with MM.

The comparison of streptokinase, an old agent, versus reteplase for the re-tunnellisation of blocked cuffed haemodialysis catheter

Background/Aim: Catheter occlusion is the most common complication occurring in patients with end-stage renal disease (ESRD) who undergo haemodialysis. The management typically involves the use of local fibrinolytic agents. However, with the emergence of novel agents, the use of older agents has declined. The purpose of the study was to compare the effectiveness of reteplase versus streptokinase (SK) in resolving haemodialysis catheter occlusion. Methods: This randomised clinical trial involved 100 patients with catheter occlusion who were equally divided into two groups of 50. One group received treatment with reteplase, while the other group received treatment with SK. The occluded catheter in the first group was instilled with 250,000 units (U) of SK, while the second group received 2 U of reteplase and the catheters were left in place for 2-6 h. Successful flushing of the catheter with a velocity of ≥ 200 rounds per minute was considered successful retunnelling. The study also evaluated the frequencies of re-injections and drug-related adverse effects. Results: The success rate of SK versus reteplase did not differ significantly (p = 0.48). However, the required time to inject the agents to achieve appropriate luminal patency was statistically higher in the reteplase-treated group (p = 0.018). None of the patients experienced major adverse effects such as bleeding or anaphylactic reactions. Conclusion: According to the findings of this study, both reteplase and SK resulted in significant recovery of luminal patency with no adverse effects. However, the lower frequency of re-injections required with SK to achieve successful rationalisation favoured the use of this agent over reteplase. Further studies are strongly recommended.

Thiopurines have no impact on outcomes of Crohn's disease patients beyond 12 months of maintenance treatment with infliximab

BackgroundThe emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines. AimsTo clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab. MethodsIn this analysis of the 2-year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C-reactive protein (CRP), and infliximab pharmacokinetics. A composite outcome based on clinical- and drug-related items was used to define treatment failure. ResultsThe study included 172 patients; of these, 35.5 % were treated with combination treatment. Overall, 18 % of patients achieved the composite outcome, without statistically significant differences between patients on monotherapy and on combination treatment (21.6% vs 11.5 %, p = 0.098). Median CRP, FC, and infliximab pharmacokinetic parameters were similar in both groups. However, in the sub-analysis by infliximab treatment duration, in patients treated for less than 12 months, the composite outcome was reached in fewer patients in the combination group than in the monotherapy group (7.1% vs 47.1 %, p = 0.021). ConclusionIn CD patients in maintenance treatment with infliximab, combination treatment does not seem to have benefits over infliximab monotherapy beyond 12 months of treatment duration.

Prevalence of Brucella melitensis and Brucella abortus Fluoroquinolones Resistant Isolates: A Systematic Review and Meta-Analysis.

Background: Brucellosis impact both animals and humans worldwide. However, using antibiotics for brucellosis remains controversial despite decades of research. Relapse can complicate treatment in this area. Since the mid-1980s, microbiologists, and physicians have studied fluoroquinolones' use for treating human brucellosis. The principal advantages of fluoroquinolones are their intracellular antimicrobial activity, low nephrotoxicity, good pharmacokinetics, and the lack of drug-level monitoring. Fluoroquinolones inhibit disease recurrence. In vitro and clinical data were used to study the prevalence of Brucella melitensis and Brucella abortus fluoroquinolone-resistant isolates. Methods: The PubMed, Scopus, Embase, and Web of Science databases were carefully searched until August 6, 2022, for relevant papers. The number of resistant isolates and sample size were used to estimate the proportion of resistant isolates, fitting a model with random effects, and DerSimonian-Laird estimated heterogeneity. Furthermore, meta-regression and subgroup analyses were used to assess the moderators to identify the sources of heterogeneity. Meta-analysis was performed using R software. Results: Forty-seven studies evaluated fluoroquinolone resistance in Brucella spp. Isolates. Fluoroquinolones have shown high in vitro efficacy against Brucella spp. The resistance rates to ofloxacin, sparfloxacin, fleroxacin, pefloxacin, and lomefloxacin were 2%, 1.6%, and 4.6%, respectively. Conclusion: Clinical in vitro tests demonstrated that fluoroquinolones can eradicate Brucella spp. Owing to first-line medication resistance, recurrence, and toxicity, it is essential to standardize the Brucella antimicrobial susceptibility test method for a more precise screening of resistance status. Fluoroquinolones are less resistant to fluoroquinolone-based treatments in modern clinical practice as alternatives to standard therapy for patients with brucellosis relapse after treatment with another regimen and in patients who have developed toxicity from older agents.

A Clinical Approach to Existing and Emerging Therapeutics in Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare but highly disabling disease of the central nervous system. Unlike multiple sclerosis, disability in NMOSD occurs secondary to relapses that, not uncommonly, lead to blindness, paralysis, and death. Recently, newer, targeted immunotherapies have been trialed and are now in the treatment arsenal. We have endeavoured to evaluate the current state of NMOSD therapeutics. This review provides a pragmatic evaluation of recent clinical trials and post-marketing data for rituximab, inebilizumab, satralizumab, eculizumab, and ravalizumab, contrasted to older agents. We also review contemporary issues such as treatment in the context of SARS-CoV2 infection and pregnancy. There has been a dramatic shift in NMOSD morbidity and mortality with earlier and improved disease recognition, diagnostic accuracy, and the advent of more effective, targeted therapies. Choosing a maintenance therapy remains nuanced depending on patient factors and accessibility. With over 100 putative agents in trials, disease-free survival is now a realistic goal for NMOSD patients.

Current and emerging medications for the management of obesity in adults.

Current and emerging medications for the management of obesity in adults.

PSMA-Targeted Radiopharmaceuticals in Prostate Cancer: Current Data and New Trials.

Radiopharmaceuticals have been utilized for men with advanced prostate cancer for decades. Older agents, seldom used today, provided palliation for bone metastatic pain. In 2013, the alpha emitter radium-223 provided a catalyst for the field by prolonging survival in men with metastatic castrate-resistant prostate cancer (mCRPC). Recently radioisotopic therapies have gained further interest with the development and FDA approval of 177 lutetium (177Lu)-PSMA-617 (also known as lutetium Lu-177 vipivotide tetraxetan). This agent targets the prostate-specific membrane antigen (PSMA) expressed on the cell surface of prostate cancer cells with a beta-emitting isotope (177Lu). This clinical review summarizes key data reported from 177Lu-PSMA-617 clinical trials, including data from the phase III VISION trial which were pivotal for regulatory approval in heavily pretreated PSMA-PET-positive patients with mCRPC. The current field of radiopharmaceuticals is in a rapid state of flux. Additional phase III trials are now ongoing in patients with mCRPC and in patients with metastatic castrate-sensitive prostate cancer. The results from these potential practice-changing trials are highly anticipated. Earlier phase trials (I/II) are in progress examining combination therapies, radiolabeled monoclonal antibodies, and novel compounds. Studies of PSMA-targeted therapies using both beta emitters such as 177Lu and novel alpha emitters such 225 actinium are in progress. During the next decade, radiopharmaceuticals will likely play a central role in the management of patients with advanced prostate cancer.

The future of psychopharmacology: challenges beyond efficacy and tolerability.

The future of psychopharmacology: challenges beyond efficacy and tolerability.

S-34-1: CENTRAL HYPERTENSION IS A NON-NEGLIGIBLE CARDIOVASCULAR RISK FACTOR

High blood pressure (BP) confers cardiovascular risk. However, the clinical value of central BP remains debatable. Central and brachial BPs are closely correlated. In most prospective investigations, elevated central and peripheral BPs were similarly associated with adverse outcomes. Outcome-driven thresholds of the central systolic BP estimated by the type I device were on average 10 mmHg lower than their brachial counterparts. Cross-classification based on the central and brachial BPs identified that nearly 10% of patients had discrepancy in their status of central and brachial hypertension. Irrespective of the brachial BP status, central hypertension was associated with increased cardiovascular risk, highlighting the importance of central BP assessment in the management of hypertensive patients. Newer antihypertensive agents, including renin-angiotensin-aldosterone system inhibitors and calcium channel blockers, were more efficacious than older agents in central BP reduction. Clinical trials are warranted to demonstrate whether controlling central hypertension with an optimized antihypertensive drug treatment will be beneficial beyond the control of brachial hypertension.

Clinical pharmacology of antidiabetic drugs: What can be expected of their use?

The pharmacotherapy of type 2 diabetes mellitus (T2DM) has markedly evolved in the last two decades. Classical antidiabetic agents (sulphonylureas, metformin, insulin) are now in competition with new glucose-lowering medications. Alpha-glucosidase inhibitors and thiazolidinediones (glitazones) were not able to replace older agents, because of insufficient efficacy and/or poor tolerability/safety. In contrast, incretin-based therapies, both dipeptidyl peptidase-4 inhibitors (DPP-4is or gliptins, oral agents) and glucagon-like peptide-1 receptor agonists (GLP-1RAs, subcutaneous injections) are a major breakthrough in the management of T2DM. Because they are not associated with hypoglycaemia and weight gain, DPP-4is tend to replace sulphonylureas as add-on to metformin while GLP-1RAs tend to replace basal insulin therapy after failure of oral therapies. Furthermore, placebo-controlled cardiovascular outcome trials demonstrated neutrality for DPP-4is, but cardiovascular protection for GLP-1RAs in patients with T2DM at high cardiovascular risk. More recently sodium-glucose cotransporter 2 inhibitors (SGLT2is or gliflozins, oral agents) also showed cardiovascular protection, especially a reduction in hospitalization for heart failure, as well as a renal protection in patients with and without T2DM, at high cardiovascular risk, with established heart failure and/or with chronic kidney disease. Thus, GLP-1RAs and SGLT2is are now considered as preferred drugs in T2DM patients with or at high risk of atherosclerotic cardiovascular disease whereas SGLT2is are more specifically recommended in patients with or at risk of heart failure and renal (albuminuric) disease. The management of T2DM is moving from a glucocentric approach to a broader strategy focusing on all risk factors, including overweight/obesity, and to an organ-disease targeted personalized approach.

446. Hyperlactatemia and Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI): Still present even with modern antiretroviral therapy (ART)

Abstract Background Hyperlactatemia and lactic acidosis represent a rare but dangerous manifestation of mitochondrial toxicity associated with NRTIs. Although mitochondrial toxicity has been linked to the NRTI class, it is more prevalent with older agents such as zidovudine (AZT), didanosine (ddI) and stavudine (d4t). Methods Prompted by the diagnosis of symptomatic hyperlactatemia in 4 people with HIV on newer NRTIs between September 2019 and December 2021, we present a single-center case series to illustrate its subtle presentation and management. Hyperlactatemia was defined as a serum lactate of 1.6-4 mmol/L and lactic acidosis was defined as a serum lactate of &amp;gt; 4mmol/L. Results 75% of the patients were male, the mean age was 57.8 years, and 100% were Caucasian. 75% (3/4) were either overweight or obese (body mass index &amp;gt; 25 kg/m2). 75% had a CD4 lymphocyte count &amp;lt; 200 cells/mm3 at the time of human immunodeficiency virus (HIV) diagnosis and 50% had the diagnosis for &amp;gt;10 years. The most common symptom reported was non-specific fatigue (100%), followed by widespread myalgias (75%). 1 patient reported severe peripheral neuropathy affecting activities of daily living and 1 patient reported palpitations and night sweats. The mean duration of symptoms prior to reporting was 27.5 months. At the time of diagnosis of symptomatic hyperlactatemia, 75% had a CD4 lymphocyte count &amp;gt; 200 cells/mm3, the mean serum lactate was 2.7 mmol/L (1.9 mmol/L - 3.9 mmol/L), 50% were on abacavir (ABC) and lamivudine (3TC), and 50% were on tenofovir alafenamide (TAF) and emtricitabine (FTC). After stopping ART for 2 weeks, mean serum lactate decreased to 0.6 mmol/L (0.4 mmol/L – 1.1 mmol/L). 100% reported an improvement in quality of life after NRTI cessation and were managed with an NRTI-sparing regimen. Clinical characteristics are noted in Table 1. Conclusion This case series highlights the insidious nature of symptoms related to NRTI-associated mitochondrial toxicity including hyperlactatemia. Management strategies are not well defined for hyperlactatemia; however, NRTI-sparing regimens may offer improvement in quality of life. Despite improved tolerability of modern ART, clinicians should be aware of and monitor for symptoms of this potentially life-threatening side effect. Disclosures Carlos Malvestutto, MD MPH, Gilead Sciences: Advisor/Consultant|Viiv Healthcare: Advisor/Consultant.

Central hypertension is a non-negligible cardiovascular risk factor.

High blood pressure (BP) confers cardiovascular risk. However, the clinical value of central BP remains debatable. In this article, we aim to briefly review the prognosis, diagnosis, and treatment of central hypertension. Central and brachial BPs are closely correlated. In most prospective investigations, elevated central and peripheral BPs were similarly associated with adverse outcomes. Outcome‐driven thresholds of the central systolic BP estimated by the type I device were on average 10 mmHg lower than their brachial counterparts. Cross‐classification based on the central and brachial BPs identified that nearly 10% of patients had discrepancy in their status of central and brachial hypertension. Irrespective of the brachial BP status, central hypertension was associated with increased cardiovascular risk, highlighting the importance of central BP assessment in the management of hypertensive patients. Newer antihypertensive agents, such as renin–angiotensin–aldosterone system inhibitors and calcium channel blockers, were more efficacious than older agents in central BP reduction. Clinical trials are warranted to demonstrate whether controlling central hypertension with an optimized antihypertensive drug treatment will be beneficial beyond the control of brachial hypertension.

Hemostatic powders for gastrointestinal bleeding: a review of old, new, and emerging agents in a rapidly advancing field.

Background and study aims Hemostatic powders are increasingly used to address limitations in conventional endoscopic techniques for gastrointestinal bleeding. Various agents exist with different compositions, characteristics, efficacy, and adverse events (AEs). We sought to review existing hemostatic powders, from preclinical to established agents. Methods A literature review on hemostatic powders for gastrointestinal bleeding was undertaken through a MEDLINE search from 2000–2021 and hand searching of articles. Relevant literature was critically appraised and reviewed for mechanism of action, hemostasis and rebleeding rate, factors associated with hemostatic failure, and AEs. Results The most established agents are TC-325 (Hemospray), EndoClot, and Ankaferd Blood Stopper (ABS). These agents have been successfully applied to a variety of upper and lower gastrointestinal bleeding etiologies, in the form of primary, combination, salvage, and bridging therapy. Few AEs have been reported, including visceral perforation, venous embolism, and self-limited abdominal pain. Newer agents include CEGP-003 and UI-EWD, which have shown results similar to those for the older agents in initial clinical studies. All aforementioned powders have high immediate hemostasis rates, particularly in scenarios not amenable to conventional endoscopic methods, but are limited by significant rates of rebleeding. Other treatments include TDM-621 (PuraStat) consisting of a liquid hemostatic agent newly applied to endoscopy and self-propelling thrombin powder (CounterFlow Powder), a preclinical but promising agent. Conclusions Rapid development of hemostatic powders and growing clinical expertise has established these agents as a valuable strategy in gastrointestinal bleeding. Further research will continue to refine the efficacy and applicability of these agents.

Update of clinical application in ceftazidime-avibactam for multidrug-resistant Gram-negative bacteria infections.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) have become a major global public health threat.Ceftazidime-avibactam (CAZ-AVI) is a newer combination of β-lactam/β-lactamase inhibitor, with activity againstcarbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Theaim of this review is to describe the recent real-world experience of CAZ-AVI for the infections due to MDR-GNB. We searched PubMed, Embase and Google Scholar for clinical application in CAZ-AVI forMDR-GNB infections. Reference lists were reviewed and synthesized for narrative review. MDRGNBinfections are associated with higher mortality significantly comparing to drug-susceptible bacterial infections.Fortunately, CAZ-AVI shows significant benefits for infections due to KPC or OXA-48 CRE, comparing to colistin,carbapenem, aminoglycoside and other older agents, even in those with immunocompromised status. The efficacyof CAZ-AVI varies in different infection sites due to CRE, which is lower in pneumonia. Early use is associated withimproved clinical outcomes. Noteworthy, when adopted as salvage therapy, CAZ-AVI is still superior to other GNBactive antibiotics. CAZ-AVI plus aztreonam is recommended as the first line of MBL-CRE infections. However, forinfections caused by KPC- and OXA-48-producing isolates, further investigations are needed to demonstrate thebenefit of combination therapy. Besides CRE, CAZ-AVI is also active to MDR-PA. However, the development ofresistance in CRE and MDR-PA against CAZ-AVI is alarming, and more investigations and studies are needed toprevent, diagnose, and treat infections due to CAZ-AVI-resistant pathogens. CAZ-AVIappears to be a valuable therapeutic option in MDR-GNB infections. Using CAZ-AVI appropriately to improveefficacy and decrease the emergence of resistance is important.

Abstract 3669: Racial/ethnic disparities in treatment with bone-modifying agents among newly diagnosed multiple myeloma patients

Abstract Introduction: There are racial/ethnic disparities in multiple myeloma (MM) treatment, including differences in the use of novel agents, stem cell transplantation, and supportive therapies such as bone-modifying agents (BMAs). BMAs reduce the frequency of fractures and skeletal-related pain, and some evidence suggests that more recently approved agents (i.e., denosumab) confer greater progression-free survival benefits than older agents (i.e., bisphosphonates). Here we describe disparities in the initiation of BMA use and uptake of denosumab among newly diagnosed MM patients by race/ethnicity. Methods: We conducted a retrospective cohort study using the nationwide Flatiron Health electronic health record-derived de-identified database. This analysis included adults (≥ 18 years) newly diagnosed with MM between January 2018 and September 2021 who initiated first-line therapy. Patient demographics and clinical characteristics were determined using structured and unstructured data, curated via technology-enabled abstraction. Cumulative incidence functions accounting for competing risks were used to estimate the initiation of BMA use within 90 days before the start of first-line MM therapy and 30 days post. We used multivariable logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for differences in the receipt of denosumab versus bisphosphonates alone (zoledronic acid or pamidronate) among patients who initiated BMA use. Results: Among 4460 newly diagnosed MM patients, 52% were White, 17% were Black, 7% were Latinx, and 2% were Asian. Overall, 2208 (50%) initiated BMA treatment, and utilization differed across racial/ethnic groups with higher rates observed among Asian (55%), White (51%), and Latinx (50%) patients compared to Black patients (44%) (P=0.023). Among patients that initiated BMAs, 53% received denosumab and 47% received bisphosphonates alone. Compared to White patients, Black (OR 1.06, 95% CI 0.83-1.36) and Asian (OR 0.82, 95% CI 0.44-1.53) patients had similar odds of receiving denosumab, whereas Latinx patients had significantly lower odds of receiving denosumab (OR 0.56, 95% CI 0.40-0.79). Conclusion: Among newly diagnosed MM patients, approximately half initiated BMAs. Substantial racial/ethnic disparities exist. For example, Black patients were less likely to receive any BMAs, and, even when treated, Latinx patients were less likely to receive denosumab. Future research should determine whether these treatment disparities impact progression-free and overall survival in real-world MM data. Citation Format: Jenny S. Guadamuz, Rebecca Rohrer, Ghulam Rehman Mohyuddin, Brian C.-H. Chiu, Pritesh R. Patel, Karen Sweiss, Erlene Seymour, Douglas Sborov, Gregory S. Calip. Racial/ethnic disparities in treatment with bone-modifying agents among newly diagnosed multiple myeloma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3669.

Article Review :Klebsiella Pneumonia: Epidemiology, Virulence Factors and Treatment

Klebsiella pneumoniae is a rare cause, excluding alcoholics, of community-acquired pneumonia. Klebsiella can resemble lung tuberculosis because it occurs with hemoptysis and lesions of the lumen. K. Pneumoniae is an infection hard to handle because of the organism's thickened capsule. Klebsiella is best handled with cephalosporins, quinolones or carbapenems of the third and fourth century. In lung inflammation, monotherapy is just as effective as combination therapy because newer agents are used. Older agents with less Klebsiella involvement were used for successful treatment in the past. Initially, the patient that we attended was believed to have pulmonary tuberculosis and the recommended medication was ceftriaxone monotherapy until it was discovered to be pneumococcal disease. The patient was initially treated with injection, then orally for 3 weeks. The purpose of this article is to address this type of bacteria, its epidemiology, virulence factors and treatment methods, due to its widespread spread within the country, which causes many respiratory diseases and can share with other pathogens such as viruses, particularly the Corona virus, which can inevitably cause death in a particular individual.

Antihypertensive Treatment and Central Arterial Hemodynamics: A Meta-Analysis of Randomized Controlled Trials.

Background: Antihypertensive treatment may have different effects on central arterial hemodynamics. The extent of the difference in effects between various antihypertensive drugs remains undefined.Methods: We conducted a systematic review and meta-analysis of randomized controlled trials that explored the effects of antihypertensive agents on both central and peripheral systolic blood pressure (SBP) and pulse pressure (PP) or central augmentation index, with a special focus on the comparison between newer [renin-angiotensin-aldosterone system (RAS) inhibitors and calcium-channel blockers (CCBs)] and older antihypertensive agents (diuretics and β- and α-blockers).Results: In total, 20 studies (n = 2,498) were included. Compared with diuretics (10 studies), β-blockers (16 studies), or an α-blocker (1 study), RAS inhibitors (21 studies), and CCBs (6 studies) more efficaciously (P < 0.001) reduced both central and peripheral SBP by a weighted mean difference of −5.63 (−6.50 to −4.76 mmHg) and −1.97 mmHg (−2.99 to −0.95 mmHg), respectively. Compared with older agents, the newer agents also more efficaciously (P < 0.001) reduced central PP (−3.27 mmHg; −4.95 to −1.59 mmHg), augmentation index (−6.11%; −7.94 to −4.29) and augmentation (−3.35 mmHg; −5.28 to –1.42 mmHg) but not peripheral PP (p ≥ 0.09). Accordingly, the newer agents reduced central-to-peripheral PP amplification significantly less than the older agents (0.11 mmHg; 0.05 to 0.17 mmHg; P < 0.001).Conclusion: Newer agents, such as RAS inhibitors and CCBs, were significantly more efficacious than older agents in their effects on central hemodynamics.