The potential of chimeric antigen receptor (CAR) T cells to successfully treat hematological cancers is widely recognized. Multiple CAR-T cell therapies are currently under clinical development, with most in early stage, during which dose selection is a key goal. The objective of this review is to address the question of dose-dependent effects on response and/or toxicity from available CAR-T cell clinical trial data. For that purpose, systematic literature review of studies published between January 2010 and May 2022 was performed on PubMed and Embase to search clinical studies that evaluated CAR-T cells for hematological cancers. Studies published in English were considered. Studies in children (age 1 patient at each dose level. Thirteen studies observed dose-related increase in disease response and 23 studies observed dose-related increase in toxicity across a median of three dose levels. Optimal clinical efficacy was seen at doses 50–100 million cells for anti-CD19 CAR-T cells and >100 million cells for anti-BCMA CAR-T cells in majority of studies. The findings suggest, for a given construct, there exists a dose at which a threshold of optimal efficacy occurs. Dose escalation may reveal increasing objective response rates (ORRs) until that threshold is reached. However, when ORR starts to plateau despite increasing dose, further dose escalation is unlikely to result in improved ORR but is likely to result in higher incidence and/or severity of mechanistically related adverse events.

CAR-T cells are widely recognized for their potential to successfully treat hematologic cancers and provide durable response. However, severe adverse events such as cytokine release syndrome (CRS) and neurotoxicity are concerning. Our goal is to assess CAR-T cell clinical trial publications to address the question of whether administration of CAR-T cells as dose fractions reduces toxicity without adversely affecting efficacy. Systematic literature review of studies published between January 2010 and May 2022 was performed on PubMed and Embase to search clinical studies that evaluated CAR-T cells for hematologic cancers. Studies published in English were considered. Studies in children (age < 18), solid tumors, bispecific CAR-T cells, and CAR-T cell cocktails were excluded. Data was extracted from the studies that met inclusion and exclusion criteria. Review identified a total of 18 studies that used dose fractionation. Six studies used 2-day dosing schemes and 12 studies used 3-day schemes to administer CAR-T cells. Three studies had both single dose and fractionated dose cohorts. Lower incidence of Grade ≥ 3 CRS and neurotoxicity was seen in fractionated dose cohorts in 2 studies, whereas 1 study reported no difference between single and fractionated dose cohorts. Dose fractionation was mainly recommended for high tumor burden patients. Efficacy of CAR-T cells in fractionated dose was comparable to single dose regimen within the same or historical trial of the same agent in all the studies. The findings suggest that administering dose fractions of CAR-T cells over 2–3 days instead of single dose infusion may mitigate the toxicity of CAR-T cell therapy including CRS and neurotoxicity, especially in patients with high tumor burden. However, controlled studies are likely needed to confirm the benefits of dose fractionation.

Ethnic differences may substantially influence the morphological characteristics of the ascending aorta, with potential implications for clinical assessment and management of aortic dilatation. This systematic review evaluated the impact of ethnicity on ascending aorta diameter and dilatation rates, highlighting the need for more tailored, ethnicity-specific care in cardiovascular practice. We identified 11 studies that measured ascending aorta dimensions using transthoracic echocardiography (TTE), computed tomography (CT), or magnetic resonance imaging (MRI). Most investigations focused on Asian, Caucasian, African American, and Hispanic populations. Data extraction revealed notable variability in baseline aortic diameters across ethnic groups. Some studies found no significant differences between Asian and Caucasian participants, whereas others reported consistently larger diameters in Chinese ethnicities compared to Caucasians and smaller diameters in African American groups. One investigation, for instance, showed that Chinese participants had ascending aorta diameters approximately 1.5 mm larger than their Caucasian counterparts. Dilatation rates also diverged: one study observed that non-White race was linked to earlier or more rapid aortic root dilation in younger populations. At the same time, another reported that Vietnamese individuals had nearly twice the annual growth rate of ascending aorta dilatation when compared to other ethnicities. Available data on prevalence varied, with some studies suggesting ascending aorta dilatation ranged from about 1.2% to 7.5% in Caucasians, 0.9% to 6.4% in African Americans, and 0.8% to 5.9% in Asians. These findings potentiate the role of ethnicity in shaping aortic dimensions, possibly through a combination of genetic predisposition, environmental factors, and lifestyle influences. Incorporating ethnic background into risk stratification may improve the accuracy of clinical assessments and help guide personalized management strategies for ascending aorta dilatation. Future research should address heterogeneity in measurement techniques, more consistently defining ethnic groups, and explore long-term outcomes to clarify whether these observed morphological differences translate into variations in morbidity and mortality.

Knee osteoarthritis significantly impacts mobility and quality of life. This condition is a leading cause of disability in aging populations, with total knee replacement commonly sought in advanced cases. Traditional nonoperative management strategies, including anti-inflammatories, corticosteroid injections, and hyaluronic acid, often provide limited relief, especially in severe cases. Recently, regenerative therapies such as amniotic suspension allografts (ASA) have emerged as promising alternatives due to their anti-inflammatory and regenerative properties, which may counteract the catabolic effects of osteoarthritis. This systematic review evaluated the efficacy and safety of ASA in reducing pain and improving function among knee osteoarthritis patients. Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, a comprehensive search of PubMed and Embase databases initially identified 1,733 studies pertaining to ASA, of which 1,575 were screened, and 9 studies ultimately met the inclusion criteria for detailed analysis of ASA in the treatment of knee osteoarthritis. Data extraction and narrative synthesis focused on outcomes such as pain reduction and functional improvement using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), as well as safety profiles. The results demonstrated notable improvements in pain scores following ASA treatment, as shown by studies reporting increases in KOOS pain scores over 6 months, which generally outperformed hyaluronic acid and saline treatments in pain reduction. Similarly, ASA treatment was associated with substantial improvements in physical function outcome scores, enhancing patients' ability to perform daily activities. Patient-reported outcomes also indicated higher quality of life and functional status, with most patients experiencing high levels of satisfaction. Additionally, ASA's safety profile was favorable, with adverse events primarily mild to moderate in nature, including a few transient events such as knee stiffness and myalgias. This systematic review highlights ASA as an effective therapeutic option for knee osteoarthritis, although further studies focusing on long-term radiographic outcomes and mechanisms of action are recommended to fully establish its benefits and optimize treatment protocols.

Background: Lateral epicondylitis impacts 1–3% of the population. It affects nearly half of all tennis players, primarily due to repetitive forearm muscle use leading to pain at the lateral elbow, particularly at the extensor carpi radialis brevis tendon. While conservative treatments resolve most cases, 4–11% of patients with persistent pain require surgery. Tenotomy is the gold standard for repair, but the research comparing the benefits of specific types of tenotomies (open, arthroscopic, percutaneous, ultrasonically assisted, and Tenex forms) is lacking. Methods: PubMed and Embase searches were conducted for articles focused on four tenotomy techniques. The inclusion criteria allowed for the use of randomized controlled trials (RCTs), prospective cohort studies, and comparative observational studies, while the exclusion criteria excluded meta-analyses. Following the PRISMA guidelines, the initial search resulted in 2327 articles. Once the inclusion and exclusion criteria were applied, 1702 articles underwent abstract screening. Finally, 232 articles proceeded to full-text screening, resulting in 37 articles undergoing data extraction. Results: The primary outcomes included functional improvement, pain relief, overall performance, and postoperative disability. The secondary outcomes included patient-reported satisfaction, return-to-work timeframes, and procedural complications. Conclusions: The tenotomy outcomes were similar, regardless of the method, indicating that discussions with patients about their specific outcome preferences may help guide tenotomy method selection.

Osteomyelitis is commonly caused by pathogens like Staphylococcus aureus, but rare organisms such as Corynebacterium minutissimum, typically associated with superficial skin infections, can also be implicated. Recognizing these atypical pathogens presents diagnostic and therapeutic challenges, especially in the presence of orthopedic hardware. We conducted a literature review yielding 25 studies and encompassing 797 patient cases, which highlights the emerging role of Corynebacterium species in osteomyelitis, particularly following trauma or surgical interventions. A 72-year-old man with a history of chronic right tibia and fibula fractures from a motor vehicle accident presented with progressively worsening leg pain over six months. Imaging revealed hardware failure and new fractures. Surgical intervention involved hardware removal, osteotomy, and placement of an external fixator. Intraoperative cultures eventually grew C. minutissimum which was resistant to ceftriaxone but sensitive to doxycycline. His antibiotic regimen was switched from intravenous cefazolin to oral doxycycline, leading to gradual pain improvement and stable clinical status. This case adds to the growing body of literature on C. minutissimum as a rare but significant cause of osteomyelitis, particularly in patients with orthopedic hardware. Our literature review emphasizes the need for clinicians to be vigilant for Corynebacterium species in cases of osteomyelitis unresponsive to standard treatments. Early recognition and targeted antimicrobial therapy guided by susceptibility testing are crucial for successful outcomes in managing atypical bone infections.