Changing Treatment Paradigms Research Articles

AML in the Elderly - When less may be more.

We herein assess the distinct biological and clinical features of AML in older patients. We emphasize the importance of pre-treatment assessment to individualize care but note the changing treatment paradigm from intensive towards non-intensive therapy. Geriatric assessments and genetic data provide predictive information that guides treatment. During the past decade the FDA approved at least nine new targeted therapies, mostly small molecule inhibitors, in AML patients of all ages. These agents have created novel therapeutic options for this poorly chemo tolerant population whose AML tends to be intrinsically resistant to such therapy. Older AML patients may now be treated with less toxic therapy that provides similar, if not superior, efficacy compared with conventional chemotherapy. Although TP53 mutant AML remains a particular unmet need, additional novel agents on the horizon provide hope for improving outcomes for older adults with AML.

The changing treatment paradigm in prolactinoma - a prospective series of 100 consecutive neurosurgical cases.

To evaluate patients with prolactinoma treated surgically in a time when elective prolactinoma surgery became routine in our center, using a comprehensive outcome set, focusing on preoperative assessments, surgical outcomes, and health-related quality of life (HR-QoL). Cohort of consecutive patients with prolactinoma undergoing surgery between January 2021 and August 2023. Clinical data were collected during multidisciplinary team (MDT) meetings/from medical records at distinct timepoints: (1) pre-surgery, (2) two weeks post-surgery, (3) six months post-surgery, and (4) follow-up (median 15.0 (10.0-24.8 months). HR-QoL was measured using the Leiden Bothers and Needs Pituitary (LBNQ-P) questionnaire. Data were described for all patients, and patients undergoing elective total resection, with additional subgroups of (a) patients undergoing a high-probability-first-total-resection, and (b) reoperations aiming for total resection. One hundred surgically treated patients with prolactinoma were included (72 female). Dopamine agonist intolerance was the most frequent indication (n=68). The surgical goal (debulking/total resection) was achieved in 90% of patients. Long-term complications occurred in 4% of patients. Seventy-eight patients underwent an elective total resection, achieving remission in 91%. The subsets of preoperatively estimated high-probability-first-total-resections (n=52), and reoperations (n=9), achieved remission in 92% and 89%, respectively. LBNQ-P Total Bothers and Total Needs scores improved significantly after surgery (p<0.001, Δ-3.4 (IQR -14.4- -0.9) and p=0.006, Δ-1.8 (IQR -11.9-1.3), respectively. High remission rates were achieved, improving HR-QoL, evidencing (repeat) prolactinoma surgery is effective in an experienced pituitary center, as highlighted in the most recent guideline (2023).

Changing treatment paradigms for membranous nephropathies.

Changing treatment paradigms for membranous nephropathies.

Frontline Therapy of CLL-Changing Treatment Paradigms.

The therapeutic landscape for chronic lymphocytic leukemia (CLL) has undergone a complete makeover following the introduction of highly effective targeted therapies, beginning with ibrutinib which first attained regulatory approval for CLL in 2014. In recent years, we have seen further refinement of therapeutic options with the development of newer-generation Bruton's tyrosine kinase inhibitors (BTKi) including acalabrutinib and zanubrutinib that improve upon the safety of ibrutinib. Additionally, venetoclax-based approaches, combined with anti-CD20 antibodies, have allowed for time-limited targeted therapeutic strategies which are particularly attractive for certain subsets of patients though have demonstrated efficacy across all subgroups. Lastly, there is an ongoing movement toward the development of time-limited strategies inclusive of both a BTKi and venetoclax that may further widen potential options. CLL patients requiring frontline therapy have a unique burden of choice between highly effective therapies that differ substantially with respect to side effect profiles and schedules. This review will focus on the frontline management of CLL in the setting of these rapidly changing options.

CHARACTERIZATION OF CUTANEOUS MELANOMA: CARCINOGENESIS BEYOND ULTRAVIOLET LIGHT

Melanoma is the most aggressive type of skin cancer due to its metastatic potential, and its incidence has increased considerably in recent decades. Sun exposure to ultraviolet A and B irradiation remains the main risk factor for the development of this type of cancer, however, other factors involved are family history, artificial tanning, melanocytic nevi, and low phototype and feomelanin photosensitization by visible light (VL). Through early diagnostic detection of the malignant lesion, it is possible to initiate therapy in an early and curative way, increasing survival with a subsequent decrease in the overall mortality rate. Advances in immunotherapy and targeted therapy have changed treatment paradigms and improved the prognosis of late-stage disease. Due to the high prevalence of the disease worldwide, the purpose of this review was to characterize the cutaneous melanoma (epidemiology, etiology, pathophysiology, clinic, diagnosis, treatment, prognosis, prevention and psychosocial aspects) such as prevention of the melanocytes against Visible Light (VL).

Risk and Response Adapted Approach for Treatment of Myeloma: Pushing Autologous Transplant Down the Hierarchy

Background &amp; Significance: In current recommendations, consolidative autologous stem cell transplant (ASCT) is essential in management of NDMM. The IFM 2009 Trial showed that RVd followed by ASCT with 1-year lenalidomide maintenance was associated with a better PFS vs. RVd with 1-year lenalidomide maintenance alone (Attal M et al, NEJM 2017). A longer follow up (8 years) of IFM trial concluded that a delayed transplant (in 2 nd line) had no impact on the PFS2 (Perrot A et al, Blood 2020). We evaluated the merit of frontline ASCT (CR1) vs. post salvage ASCT (CR2) in light of indefinite maintenance therapy post novel triplet/quadruplet induction. Material &amp; Methods: We conducted this retrospective analysis, of symptomatic myeloma patients who underwent ASCT at Rajiv Gandhi Cancer Centre, Delhi between April 2017 and October 2022. Patients were segregated into 2 cohorts; a) ASCT CR1- who received 4 to 6 cycles of RVd (+/- Anti CD38 antibody) induction followed by transplant and indefinite maintenance and b) ASCT CR2- patients who relapsed after 4-6 cycles of RVd induction+maintenance then salvaged with 2 to 6 cycles of novel agent-based therapy (Carfilzomib/ Pomalidomide/ Daratumumab) followed by ASCT and indefinite maintenance. Patient characteristics were balanced for age, gender, ISS, RISS and high risk cytogenetics (Del p53, t(4;14), t (14;16), 1qGain, 1pDel, 13qDel). Response was assessed as per IMWG criteria. PFS was defined as the time from induction/salvage to progression on next line of therapy or death. Results: Of 161 patients included, we compared outcomes of ASCT CR 1 (N=122) to ASCT CR-2 (N=39). All patients received maintenance (PI/IMID or in combination) post ASCT. Significant patients in ASCT-CR2 received novel salvage therapy (Carfilzomib/ Pomalidomide/ Daratumumab) (CR1-14 % vs CR2-100%, p value- &amp;lt;0.01). 86% patients in ASCT CR1 received RVd. Both groups were substantially exposed to Lenalidomide. Median time from diagnosis to transplant was 5.9 months (range 4-12) in ASCT- CR1 group and 29.5 months (range 18-64) in ASCT CR2 group (p value- 0.004). After a median follow up of 44 months for ASCT CR1 vs. ASCT CR2, the ORR (97% vs. 95.4%, p=0.88) and CR (85% vs. 78%, p=0.67), respectively. 42.6% patients in ASCT CR1 and 38.4% patients in ASCT CR2 relapsed (p value- 0.4%). The median PFS for both groups (ASCT CR1 and ASCT CR2) were similar 45 months and 43 months, respectively, (p value- 1.09). The 1-, 3- and 5-year PFS showed a similar trend across cohorts (CR-1: 95%, 59.1%, 39.7% and CR-2: 84%, 57.1%, 41.3%). Patients with high-risk cytogenetics in ASCT CR 1 (N=50) had a better median PFS (25 months) compared to ASCT CR2 (N=16, median PFS=17.9 months, p=0.059), fig:1 though statistically insignificant. Table:1 No difference in PFS for standard risk noted (p=0.38). On regression analysis, factors predictive of progression were: ISS stage III (univariate only), high-risk cytogenetics, IMID based maintenance therapy. We noted better PFS in patients receiving &amp;gt;24 months of maintenance. Depth of response prior to transplant, Melphalan dosage and remission (CR1 vs CR2) did not predict progression. Conclusion: In the light of above findings, does transplant decision need re-sequencing? Our findings are not in agreement with the hypothesis that exposure to novel agents in relapsed/refractory settings leads to resistant clone selection under stress. The pattern of relapse in standard risk myeloma remains same across lines of therapy. Excellent response rates are observed with novel agents at relapse therefore delaying transplant appears reasonable in standard risk. High-risk myeloma represents a unique subset where patients experience early/aggressive relapse indicating that current therapy offers little modification of kinetics or natural history of disease. Changing treatment paradigm based on disease risk and response appears pragmatic. Myeloma is the disease of elderly with plethora at hand, its time to individualize.

Comparative analysis of clinical efficacy and safety of omalizumab biosimilar in the treatment of patients with chronic spontaneous urticaria

BACKGROUND: Importance of optimizing strategy for treatment of chronic spontaneous urticaria is highly becoming relevance for the clinicians. Nowadays monoclonal antibodies are preferred option of treatment the refractory chronic spontaneous urticaria, main of that is omalizumab.&#x0D; AIM: to establish comparative analysis of the efficacy and safety of Genolair (JSC Generium, Russia) and Xolair (Novartis Pharma AG, Switzerland) in the treatment of patients with chronic spontaneous urticaria.&#x0D; MATERIALS AND METHODS: A 36-week, open parallel-group study was conducted. Were included 43 adult patients with chronic spontaneous urticaria who were resistant to ongoing therapy with standard and escalated doses of second-generation H1-antihistamines. All patients were divided into 2 groups: the main group (MG; n=18) ― patients who administrated Genolair; the comparison group (CG; n=25) ― patients who firstly administrated Xolair and then switching therapy to Genolair. Throughout the study period, patients completed questionnaires on the assessment of disease activity (UAS 7), urticaria control (UCT), quality of life index (DLQI). Additionally, the level of total IgE in blood serum was assessed. For statistical data processing, EXCEL 2010 and STATISTICA 7.0 software packages were used.&#x0D; RESULTS: After 4 weeks from the start of monoclonal antibody therapy, patients in both groups were responders to omalizumab. At the same time, there were no significant differences when comparing scores on the UAS 7, UCT scale between patients of the MG and the CG during the entire observation period (p 0.05). The change in treatment paradigm in CG also did not have a statistically significant effect on the indicators of urticaria activity and disease control (p 0.05). At the same time, the quality of everyday life changed more positively in the MG, which was reflected in a more pronounced change in the DLQI index at the time of the control assessment since 20 weeks of therapy (p=0.032). An increase in the level of total IgE in the blood serum of all patients with chronic spontaneous urticaria after the initiation of a course of immunobiological therapy was demonstrated, while there were no statistically significant intergroup differences in relation to changes in this laboratory parameter (p 0.05).&#x0D; CONCLUSION: During the treatment of patients with severe chronic spontaneous urticaria, resistant to ongoing therapy with standard and escalated doses of second-generation H1-antihistamines, comparable clinical efficacy and safety of the study drug Genolair and the reference drug Xolair were shown.

Analysis of the Status and Future Direction for Digital Therapeutics in Children and Adolescent Psychiatry.

Digital therapeutics based on software, such as artificial intelligence, virtual reality, games, and smartphone applications, are in the spotlight as new therapeutic alternatives in child and adolescent psychiatry. It draws attention to overcoming conventional therapeutics' limitations, such as toxicity, cost, and accessibility, and encourages patients to participate in the treatment attractively. The growth potential of the digital therapeutics market for psychiatric disorders in children and adolescents in Korea and abroad has been highlighted. Clinical studies and Food and Drug Administration approvals for digital therapeutics have increased, and cases approved by the Ministry of Food and Drug Safety have emerged in Korea. As seen above, digital transformation in child and adolescent psychiatry will change treatment paradigms significantly. Therefore, as this new field has just begun to emerge, it is necessary to verify the effectiveness and scope of the application of digital therapeutics and consider preparing a compensation system and institutional arrangements. Accordingly, this study analyzed the development trends and application status of digital therapeutics in children and adolescents and presented limitations and development directions from the perspective of application in healthcare. Further, the study is expected to identify the utility and limitations of digital therapeutics for children and adolescents and establish effective application measures.

Neoadjuvant Immunotherapy for Patients with dMMR/MSI-High Gastrointestinal Cancers: A Changing Paradigm.

Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with the MMR-D/MSI-H genotype often carry a higher tumor mutation burden with frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response seen with immune checkpoint inhibitors (ICIs), which are orchestrated by MANA-primed effector T cells, resulted in the rapid development of these novel therapeutics within the landscape of MSI-H gastrointestinal cancers. Recently, several clinical trials have utilized ICIs as potential neoadjuvant therapies for MSI-H gastrointestinal cancers and demonstrated deep clinical and pathological responses, creating opportunities for organ preservation. However, there are potential challenges to the neoadjuvant use of ICIs for certain disease types due to the clinical risk of overtreatment for a disease that can be cured through a surgery-only approach. In this review article, we discuss neoadjuvant management approaches with ICI therapy for patients with MSI-H gastrointestinal cancers, including those with oligometastatic disease. We also elaborate on potential challenges and opportunities for the neoadjuvant utilization of ICIs and provide further insight into the changing treatment paradigm of MMR-D/MSI-H gastrointestinal cancers.

Impact of Changes in Treatment Paradigms on Survival in Oral Squamous Carcinoma-a Population-Level Study.

The online version contains supplementary material available at 10.1007/s13193-023-01790-0.

Saphenous sparing treatments: The ASVAL Method

The ASVAL method is based on a bottom-up concept of the evolution of venous disease from the tributaries to the saphenous axes, as opposed to the traditional top-down theory where reflux, conversely, appears first on the saphenous axes and then spreads to the tributaries. The bottom-up evolution has led to a change in treatment paradigm, no longer based on effective suppression of saphenous reflux, but on reversibility of the latter by ablation of the varicose tributaries, eliminating the filling effect at the origin of the hemodynamic disturbance. As the ASVAL strategy has its limits, depending on the stage of progression of saphenous damage, it is necessary to establish the indications where it can be applied, before the saphenous vein is irreversibly damaged (diameter larger than 8 mm, multiple ectasia, extended reflux above and below knee), or the clinical staged too advanced (skin changes). Various authors have reported on these criteria for applying the ASVAL method in the right indications considering hemodynamic data (ostial reflux, extent of truncal reflux), anatomical data (saphenous diameter, reflux location, volume of varicose reservoir) and clinical data (age, nulliparity, trophic disorders, presence of symptoms). Complications and side effects are limited if the indications and principles of the miniphlebectomy technique are respected. All the cohort studies reported show that after treatment using the ASVAL method (removal of varicose tributaries and ad integrum respect for the saphenous vein), reflux abolition is achieved in between 50% and 80% of cases, depending on the patients selected. Above all, these studies show that improvement in symptoms and quality of life is systematic, whatever the result on the saphenous vein. A recent randomized controlled trial shows that endovenous laser and ASVAL are clinically equivalent, with a cost/effectiveness ratio in favor of ASVAL. In conclusion, The ASVAL method leads to an alternative concept of an ascending or multifocal evolution starting on the epifascial tributaries and enabling to set an individualized “à la carte treatment” since every patient has a different clinical and hemodynamic situation of the disease at the time of treatment, which cannot match to a “one size fits all” that represents the traditional strategy. We have now at our disposal simple tools to evaluate the patients, select the good indications and perform properly the ASVAL method by mini-phlebectomy.

Isocitrate dehydrogenase mutations in gliomas: A review of current understanding and trials.

Isocitrate dehydrogenase (IDH) is a key enzyme in normal metabolism and homeostasis. However, mutant forms of IDH are also defining features of a subset of diffuse gliomas. In this review, we highlight current techniques targeting IDH-mutated gliomas and summarize current and completed clinical trials exploring these strategies. We discuss clinical data from peptide vaccines, mutant IDH (mIDH) inhibitors, and PARP inhibitors. Peptide vaccines have the unique advantage of targeting the specific epitope of a patient's tumor, inducing a highly tumor-specific CD4+ T-cell response. mIDH-inhibitors, on the other hand, specifically target mutant IDH proteins in cancer cell metabolism and thus help halt gliomagenesis. We also explore PARP inhibitors and their role in treating diffuse gliomas, which exploit IDH-mutant diffuse gliomas by allowing the persistence of unrepaired DNA complexes. We summarize various completed and current trials targeting IDH1 and IDH2 mutations in diffuse gliomas. Therapies targeting mutant IDH have significant promise in treating progressive or recurrent IDH-mutant gliomas and may significantly change treatment paradigms in the next decade.

Mainstreaming of genomics in oncology: a nationwide survey of the genomics training needs of UK oncologists

Genomics is rapidly changing treatment paradigms for cancers, obligating oncologists to have good genomics knowledge. Through this survey, we aimed to assess the current understanding of cancer genomics among UK oncologists. We conducted a web-based nation-wide self-assessment survey of the cancer genomics knowledge of UK clinical and medical oncology trainees and consultants. In total, 150 oncologists (81 consultants and 69 trainees) responded, representing 10% of UK oncologists.Formal training in genomics had not been received by 38.7% of oncologists and 92.7% identified a need for additional genomics training.In total, 71.3% self-reported to have good knowledge of defining somatic and germline mutations, falling to 35.3% for understanding principles of gene expression and regulation. Knowledge of cancer-predisposing syndromes was highest for Lynch syndrome (40.7% good knowledge) and lowest for multiple endocrine neoplasia (14.0% good knowledge).Overall, 49.0% of respondents had consented patients for germline testing, but 80.7% reported a lack of training in genetic counselling. Large knowledge gaps have been identified through this survey, highlighting the need for incorporation of improved formal training in cancer genomics for consultants and trainees, with an aim to equip oncologists for advances in clinical practice and to take up genetic mainstreaming confidently.

465TiP Evaluation of quality of life and functional outcomes following limb salvage surgery in extremities sarcomas

Management of musculo-skeletal cancers patients has changed significantly with change in treatment paradigm from amputation to limb conservation. Limb Salvage Surgery (LSS) is now the standard of care. Moreover, increase in survival rates following advancement in the available multimodality treatment has lead to increased interest regarding the quality of life (QOL) and functional outcomes of the survivor patients. Unfortunately, all the QoL studies in published literature pertain to western population.

Characterizing Metastatic Non-Small Cell Lung Cancer Presenting to an Academic Medical Center in an Era of Changing Treatment Paradigms

<h3>Purpose/Objective(s)</h3> Recent randomized trials have supported the existence of a limited metastatic disease state that may benefit from definitive local therapy in patients with non-small cell lung cancer (NSCLC). Due to limits of current staging systems, it is not possible to evaluate the spectrum of metastatic disease with commonly used cancer registries. The purpose of this study is to evaluate the extent and burden of metastatic disease in NSCLC patients presenting to an academic medical center and determine the incidence of patients meet existing criteria for ‘oligometastatic' disease. <h3>Materials/Methods</h3> An observational cohort of patients with de novo or recurrent metastatic NSCLC diagnosed from 2016 to 2019 were randomly sampled from a tumor registry. Patients were excluded if they did not receive any tumor directed therapy. Baseline demographic, staging, and treatment data were obtained from the registry and structured electronic health record (EHR) data. Manual chart review was performed to obtain details on metastatic presentation, local therapy, and progression. Definitions for oligometastatic disease were obtained from NRG LU002, MDACC Gomez et al., SINDAS and SABR COMET clinical trials. <h3>Results</h3> One hundred eight patients were evaluated with a median age of 68 years (range, 22 – 92) at initial diagnosis and median follow up of 23.5 months. 75% of patients (n=81) presented with de novo metastatic disease, while 25% (n=27) presented with recurrence. Histologies included adenocarcinoma (66%, n=71), squamous cell carcinoma (9%, n=10), and ‘other' (20%, n=22). Targetable mutations were present in 31% (n=34) of patients including EGFR (n=27) and ALK (n=2) and MET (n=6). 41% (n=48) of patients had a suspected malignant effusion present at the time of diagnosis. Common sites of metastases included lymph nodes (n=85, 79%), lungs (n=60, 56%), brain (n=49, 45%), and bone (n=48, 44%). 19% (n=21) presented with only one total metastatic tumor, 29% (n=31) with 2-3, 17% (n=18) with 4-5, 19% (n=21) with 6-10, and 16% (n=17) with 10+ tumors. 28% (n=30) of all patients were eligible for at least one oligometastatic NSCLC clinical trial, with 16% meeting eligibility for LU-002 (n=17), 19% for MDACC (n=22), 16% for SABR COMET (n=17), and 5% for SINDAS (n=5). Among those that met trial criteria for oligometastatic disease 40% (n=12) were treated with local therapy including surgery or radiation. <h3>Conclusion</h3> Most patients presenting with metastatic NSCLC to our institution had initial de novo metastatic presentation, multi-organ involvement, and adenocarcinoma histology. Roughly one third of patients were classified as oligometastatic using existing trial criteria. A minority of oligometastatic patients were treated with local therapy after metastatic diagnosis during the study period.

Toxicity Management in the Era of Changing Treatment Paradigms for Locally Advanced Rectal Cancer.

Treatment paradigms for locally advanced rectal cancer have evolved over the last several decades. Patients now have several different "standard" options with different radiation courses, sequencing of treatment modality and in some scenarios potentially avoidance of surgery. In this context, an updated understanding of treatment toxicity is needed to help patients make informed decision regarding their treatment. The RAPIDO study showed no difference in cumulative rate or grade of toxicity between short and long course radiation. Based upon our experience, patients with short course radiation tend to present with acute symptoms 1-2weeks after completion of radiation, while those receiving long course chemoradiation have symptoms towards the end of treatment. Treatments that may be helpful particularly for short course radiation toxicity include Bentyl (dicycloverine) and steroids. The most common toxicities from radiation are due to bowel and rectal inflammation leading to diarrhea, cramping, and urgency. The combination of surgery and radiation can exacerbate these symptoms. The most common late toxicity in patients receiving doublet chemotherapy is neurotoxicity. Rates of infertility differ in men versus women; all efforts for fertility preservation should be completed prior to initiation of any therapy.

The Role of Immunotherapy in Pancreatic Cancer.

Pancreatic adenocarcinoma remains one of the most lethal cancers globally, with a significant need for improved therapeutic options. While the recent breakthroughs of immunotherapy through checkpoint inhibitors have dramatically changed treatment paradigms in other malignancies based on considerable survival benefits, this is not so for pancreatic cancer. Chemotherapies with modest benefits are still the cornerstone of advanced pancreatic cancer treatment. Pancreatic cancers are inherently immune-cold tumors and have been largely refractory to immunotherapies in clinical trials. Understanding and overcoming the current failures of immunotherapy through elucidating resistance mechanisms and developing novel therapeutic approaches are essential to harnessing the potential durable benefits of immune-modulating therapy in pancreatic cancer patients.

Short-term Complications for Proximal Humerus Fracture Surgery Have Decreased: An Analysis of the National Surgical Quality Improvement Program Database.

Multiple surgical treatments exist for proximal humerus fractures (PHFs), but current practice patterns and short-term complication profiles remain poorly understood. This is in part due to changes in treatment paradigms over the past decade. A more thorough understanding of the evolution in management over this time as well as an appreciation of the preoperative factors associated with both the chosen surgical modality and short-term complications will help inform future surgical considerations. In this study, we sought to: (1) characterize trends in the surgical management of PHFs over time, including usage rates of various surgical modalities and changes in complication rates; (2) identify preoperative variables associated with the selection of surgical modality; and (3) assess the independent covariates of acute 30-day complications, including demographic variables, injury characteristics, and treatment type. The National Surgical Quality Improvement Program (NSQIP) database was queried using Current Procedural Terminology and ICD-9 and ICD-10 codes to identify individuals with PHF undergoing open reduction and internal fixation (ORIF), hemiarthroplasty (HA), or reverse total shoulder arthroplasty (RTSA) from 2007 to 2018. The NSQIP database was utilized because of its collection of detailed preoperative demographic information and large repository of clinically derived data, which is felt to be more accurate than claims or administrative data. In total, 5889 patients with PHFs met the inclusion criteria. Patients 17 years or older were included. Patients with isolated greater tuberosity, humeral shaft, and distal humerus fractures; nonunions; malunions; and those undergoing revision procedures were excluded. A Cochran-Armitage test was used to evaluate surgical trends over time. Multivariable logistic regression models were created to identify covariates associated with surgical modality and complications. Although complications were either classified as major or minor, specific complications were also individually analyzed to avoid potentially misleading conclusions associated with pooling. The proportion of patients with PHFs undergoing RTSA (4% in 2007 and 34% in 2018; p < 0.001) and ORIF (46% in 2007 and 57% in 2018; p < 0.001) increased over time, and the proportion of those undergoing HA (50% in 2007 and 9% in 2018; p < 0.001) decreased. Across each surgical modality, minor complication rates decreased over time (RTSA: 10% in 2018; p < 0.001; ORIF: 5% in 2018; p = 0.01; and HA: 6% in 2018; p = 0.01). After controlling for confounding variables like diabetes, chronic obstructive pulmonary disease, congestive heart failure, dialysis, and preoperative blood transfusion, the following factors were independently associated with an increased odds of a patient undergoing RTSA rather than HA: older age, higher BMI, independent functional status, and smoking. The following factors were independently associated with a decreased odds of a patient undergoing ORIF rather than RTSA and HA: older age, higher BMI, higher American Society of Anesthesiologists (ASA) classification, smoking, steroid/immunosuppressant use, as well as three- and four-part fractures. After controlling for age, ASA classification, functional status, and preoperative blood transfusion, we also found that in the latter part of the study period, arthroplasty (RTSA and HA) was no longer independently associated with 30-day major or minor complications compared with ORIF. The increasing utilization of RTSA and decreasing short-term complication rates for fixation and arthroplasty alike represent a substantial change compared even with recent historic norms in the management of proximal humerus fractures. Quantifying demographics, injury characteristics, and comorbidities associated with both the choice of surgical modality and complications serves as the groundwork for decision support tools, which can inform patients and surgeons of the probability of a particular surgical modality being chosen and the risk of complications, based on national benchmarks. Future studies should investigate longer term complication rates, as many differences between the approaches being compared might occur beyond the perioperative period and our study had no means to address questions about complications beyond that period, but obviously those must be considered when choosing a treatment for patients with these injuries. Future work might also investigate the mechanisms behind the decreasing rates of short-term complications. Level III, therapeutic study.

Global epidemiology of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that predominantly affects the joints. The prevalence of RA varies globally, with generally a higher prevalence in industrialized countries, which may be explained by exposures to environmental risk factors, but also by genetic factors, differing demographics and under-reporting in other parts of the world. Over the past three decades, strong trends of the declining severity of RA probably reflect changes in treatment paradigms and overall better management of the disease. Other trends include increasing RA prevalence. Common risk factors for RA include both modifiable lifestyle-associated variables and non-modifiable features, such as genetics and sex. A better understanding of the natural history of RA, and of the factors that contribute to the development of RA in specific populations, might lead to the introduction of specific prevention strategies for this debilitating disease.

Immunotherapy-Based Treatments of Hepatocellular Carcinoma: AJR Expert Panel Narrative Review.

The advent of immunotherapy for patients with hepatocellular carcinoma (HCC) has changed the treatment landscape and conferred a survival benefit on patients with advanced HCC, who typically have a very poor prognosis. The most pronounced improvements in response, as documented by standardized response criteria based on CT or MRI, have been achieved when immunotherapy is combined with other systemic or locoregional therapies. Immune checkpoint inhibitor treatments result in unique patterns on CT and MRI that challenge the application of conventional response criteria such as RECIST, modified RECIST, and European Association for the Study of the Liver criteria. Thus, newer criteria have been developed to gauge therapy response or disease progression for patients receiving immunotherapy, including immune-related RECIST (iRECIST) and immune-modified RECIST (imRECIST), though these remain unvalidated. In this review, we describe the current landscape of immunotherapeutic agents used for HCC, summarize the results of published studies, review the pathobiologic mechanisms that provide a rationale for the use of these agents, and report on the status of response assessment for immunotherapy either alone or in combination with other treatment options. Finally, consensus statements are provided to inform radiologists about essential considerations in the era of a rapidly changing treatment paradigm for patients with HCC.