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Lenalidomide, bortezomib, and dexamethasone (RVd) have previously been established as standard-of-care induction therapy for newly diagnosed multiple myeloma (NDMM). More recently, randomized phase 3 data have demonstrated the benefit of the addition of daratumumab (Dara-RVd) to the RVd backbone in terms of improved both depth of response and long-term survival benefit as measured by progression-free survival (PFS). Our group has previously published on a historical cohort of 1000 NDMM patients uniformly treated with RVd induction with impressive both PFS and overall survival. Here, we present a comparative analysis of our RVd cohort with a recent cohort of 326 patients induced with Dara-RVd at our institution with intent to transplant. This analysis demonstrates the utility of this regimen in real-world clinical practice and provides additional insights into D-RVd performance in patient subsets often underrepresented in clinical trials, as well as the impact of daratumumab in maintenance for NDMM patients.

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The recently published DreaMM-7 and -8 trials1,2 demonstrate the benefit of triplet combination regimens including the anti-BCMA antibody drug conjugate belantamab mafodotin. Here, we describe the findings of these trials including efficacy and safety data and provide commentary on the implications for future use of belantamab in the relapsed myeloma space.

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A wide spectrum of benign and malignant primary mesenchymal tumors and tumor-like lesions of the spleen has been recently included under the umbrella term 'stroma-derived' neoplasms and tumor-like lesions. These include dendritic cell neoplasms such as follicular dendritic cell sarcoma, EBV-positive inflammatory follicular dendritic cell sarcoma, and fibroblastic reticular cell tumor; smooth muscle and myofibroblastic lesions such as inflammatory pseudotumor, EBV-associated smooth muscle tumor and undifferentiated pleomorphic sarcoma as well as a diverse spectrum of vascular and vascular-stromal tumors and tumor-like lesions. While some tumor and tumor-like lesions are unique to the spleen, others may also occur in diverse extra-splenic viscera. These tumors and tumor-like lesions demonstrate characteristic histopathology, immunocytochemistry and biological behavior. While cross-sectional imaging studies allow detection, staging and limited characterization of these splenic lesions, histopathological confirmation permits optimal management and surveillance strategies.

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There is a diverse group of non-gastrointestinal stromal tumor (GIST), mesenchymal neoplasms of the gastrointestinal (GI) tract that demonstrate characteristic pathology and histogenesis as well as variable imaging findings and biological behavior. Recent advancements in tumor genetics have unveiled specific abnormalities associated with certain tumors, influencing their molecular pathogenesis, biology, response to treatment, and prognosis. Notably, giant fibrovascular polyps of the esophagus, identified through MDM2 gene amplifications, are now classified as liposarcomas. Some tumors exhibit distinctive patterns of disease distribution. Glomus tumors and plexiform fibromyxomas exhibit a pronounced affinity for the gastric antrum. In contrast, smooth muscle tumors within the GI tract are predominantly found in the esophagus and colorectum, surpassing the incidence of GISTs in these locations. Surgical resection suffices for symptomatic benign tumors; multimodality treatment may be necessary for frank sarcomas. This article aims to elucidate the cross-sectional imaging findings associated with a wide spectrum of these tumors, providing insights that align with their histopathological features.

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BACKGROUND: Social comparison, the process of evaluating one's characteristics in relation to others, influences individuals' self-perception and behavior. However, instruments are scarce for assessing social comparison in the medical setting. OBJECTIVES: Our aim was to develop and validate a new scale for assessing social comparison. MATERIALS AND METHODS: Seven statements were developed, encompassing the perceived normality of having rashes, the tendency to compare their situation with others, and the emotional response when seeing someone better or worse off than themselves. The instrument was piloted in 15 patients for readability and face validity, then prospectively validated using modern psychometric methods in 1,053 adult patients with eczema or psoriasis from three tertiary dermatological centers in Singapore. RESULTS: Of 1,053 adult patients, 802 (76.2%) had eczema, and 251 (23.8%) had psoriasis. Exploratory factor analysis (using a 70% sample split) showed a single factor model comprising three questions (Eigenvalue: 1.4). Confirmatory factor analysis with the remaining 30% of the sample confirmed an excellent model fit. Cronbach's alpha was 0.7, and inter-item correlations ranged from 0.42 to 0.46. In the Rasch analysis, item fit statistics and item characteristic curves showed appropriate discrimination between response options, although reliability was suboptimal with a person separation reliability of 0.63. CONCLUSIONS: Comprising 3 questions, the newly derived social comparison scale showed acceptable psychometrics as a measure of social comparison for clinical and research purposes in dermatology. Its brief nature likely results from its brevity and applicability to conditions beyond eczema and psoriasis, which warrants further investigation.

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PURPOSE: To describe amniotic membrane augmentation for enucleation after chemotherapy in retinoblastoma. METHODS: This was a retrospective study of patients with retinoblastoma who underwent enucleation. The study also evaluated the utility of amniotic membrane grafting in enucleation after chemotherapy in eyes with retinoblastoma. RESULTS: In this study, 110 eyes of 107 patients were analyzed, and 49 patients had previous systemic chemotherapy, 13 eyes had previous intra-arterial chemotherapy, and 7 eyes had external beam radiation. Amniotic graft was used in 8 eyes (5 following IAC, 2 following systemic chemotherapy, and 1 after both). After IAC, 3 of 7 eyes without amniotic graft had implant exposure compared to 0 of 6 eyes with amniotic graft (P = .05). Pathological examination of the conjunctiva after intra-arterial chemotherapy showed goblet cell hypoplasia that hinders wound healing. CONCLUSIONS: Amniotic membrane augmentation improves wound integrity in patients with retinoblastoma, especially following intra-arterial chemotherapy. [J Pediatr Ophthalmol Strabismus. 2024;61(4):291-295.].

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BACKGROUND: From 2013 to 2020, Arizona state trauma system expanded from seven to thirteen level 1 trauma centers (L1TCs). This study utilized the state trauma registry to analyze the effect of L1TC proliferation on patient outcomes. METHODS: Adult patients age≥15 in the state trauma registry from 2007-2020 were queried for demographic, injury, and outcome variables. These variables were compared across the 2 time periods: 2007-2012 as pre-proliferation (PRE) and 2013-2020 as post-proliferation (POST). Multivariate logistic regression was performed to assess independent predictors of mortality. Subgroup analyses were done for Injury Severity Score (ISS)≥15, age≥65, and trauma mechanisms. RESULTS: A total of 482,896 trauma patients were included in this study. 40% were female, 29% were geriatric patients, and 8.6% sustained penetrating trauma. The median ISS was 4. Inpatient mortality overall was 2.7%. POST consisted of more female, geriatric, and blunt trauma patients (P < .001). Both periods had similar median ISS. POST had more interfacility transfers (14.5% vs 10.3%, P < .001). Inpatient, unadjusted mortality decreased by .5% in POST (P < .001). After adjusting for age, gender, ISS, and trauma mechanism, being in POST was predictive of death (OR: 1.4, CI:1.3-1.5, P < .001). This was consistent across all subgroups except for geriatric subgroup, which there was no significant correlation. DISCUSSION: Despite advances in trauma care and almost doubling of L1TCs, POST had minimal reduction of unadjusted mortality and was an independent predictor of death. Results suggest increasing number of L1TCs alone may not improve mortality. Alternative approaches should be sought with future regional trauma system design and implementation.

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BACKGROUND: Root coverage procedures are very technique sensitive and require patients' compliance for successful treatment outcomes. Post operative complications can influence patients' acceptance of treatment and compromise further periodontal maintenance. AIM: The aim of this study was to evaluate the frequency and severity of complications after a modified coronally advanced flap procedure. METHODS AND MATERIALS: A total of 78 modified coronally advanced flap procedures were performed in 42 patients for root coverage. Duration of surgical procedure, history of smoking, gender, and age were recorded for each patient. A questionnaire was given to every patient to fill in at first post operative week regarding their experience of postoperative pain, swelling, and bleeding. RESULTS: Pain and duration of surgery had a correlation (OR: 1.05, P < 0.05). Post operative bleeding was significantly correlated with duration of surgery (OR: 1.03, P < 0.05). Current smokers experienced post operative swelling (P < 0.05). However, post operative pain in current smokers was not significantly different (P > 0.05) as compared to nonsmokers. Descriptive statistics were expressed as mean and standard deviations. Odd's ratio was obtained to evaluate risk indicators for moderate to severe types of complications. P < 0.05 was considered as significant. CONCLUSIONS: The duration of the surgery, long duration, and the presence of smoking can increase the frequency and severity of post operative complications.

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Amyloid is an extracellular deposition of Congo red positive material which shows apple green birefringence under polarized light. A cytopathologist can uncommonly encounter such cases. Among the reported cases, a fine-needle aspiration (FNA) of amyloid is frequently misinterpreted as acellular nondiagnostic material. We report a case of amyloidoma of the right upper arm in a 68-year-old man with history of renal transplantation for diabetic nephropathy who presented with loss of appetite and weight loss. Physical exam showed a 7 cm hard nodular subcutaneous mass in the right upper arm. FNA yielded abundant acellular, irregular fragments of dense material, which was Congo red positive with apple green birefringence by polarized light, consistent with amyloid. Further subtyping of the amyloid by mass spectrometry, showed AIns (insulin)-type amyloid deposition. After further questioning, the patient admitted to injecting insulin at the same site for many years. Awareness of the cytological features is important for diagnosis. This is especially important when dealing with uncommon sites and without adequate clinical information.

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INTRODUCTION: Data concerning the global burden of hidradenitis suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalences have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease. METHODS: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital or a private/family medicine clinic. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Approximately ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N). CONCLUSION: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation and synthesized using a random-effects model. The novel standardization of the Global Prevalence Studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies.

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BACKGROUND: Amyloid, presenting as a mass, is termed amyloidoma. Among the reported cases, fine-needle aspiration (FNA) of amyloid is often misinterpreted as acellular nondiagnostic material. METHODS: A computer search of all FNAs was performed and cases diagnosed as amyloidoma were identified. RESULTS: Among 11,956 cases and 20,634 FNAs, there were six cases and 12 FNAs of amyloidoma. One case with mucin/myxoid matrix was misinterpreted as amyloid, which on our review was Congo red negative. All five other cases of amyloidoma were adequate for evaluation. The smears showed most of the aspirated contents in the middle of the slide and it did not spread when smeared. The amyloid was present as large chunks of waxy, smooth, orangophilic/cyanophilic fragments on Papanicolaou stain and as basophilic fragments on Diff-Quik stain in a clean background. In cases with lymphoma/myeloma, there were admixed lymphocytes and/or plasma cells. Unlike fibrous tissue, amyloid aspirates well and provides adequate material for interpretation. The clean background distinguishes it from mucin/myxoid matrix. Congo red stain was positive with apple green birefringence in all five cases. Further subtyping by mass spectrometry showed AL (κ) type in three patients and AIns (insulin) type in one patient. In one patient with lymphoma, the subtyping was not done. CONCLUSION: FNA of amyloidoma is rare (0.04%), but an optimal method for diagnosis and subtyping, avoiding unwanted surgical interventions. Although mistaken for fibrous tissue, which aspirates poorly, abundant acellular orangophilic/cyanophilic material on FNA should raise a suspicion for amyloid. Unlike mucin/myxoid matrix, amyloid does not smear the background.

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BACKGROUND: Several registries for hidradenitis suppurativa (HS) already exist in Europe and the USA. There is currently no global consensus on a core dataset (CDS) for these registries. Creating a global HS registry is challenging, owing to logistical and regulatory constraints, which could limit opportunities for global collaboration as a result of differences in the dataset collected. The solution is to encourage all HS registries to collect the same CDS of information, allowing registries to collaborate. OBJECTIVES: To establish a core set of items to be collected by all HS registries globally. The core set will cover demographic details, comorbidities, clinical examination findings, patient-reported outcome measures and treatments. METHODS: Beginning in September 2022, 20 participants - including both clinicians with expertise in HS and patient advocates - from eight countries across three continents participated in a Delphi process consisting of four rounds of voting, with all participants completing each round. A list of potential items for inclusion in the core set was generated from the relevant published literature, including systematic reviews of comorbidities in HS, clinical and examination findings, and epidemiology. For disease severity and progression items, the Hidradenitis SuppuraTiva Core outcome set International Collaboration (HiSTORIC) core set and other relevant instruments were considered for inclusion. This resulted in 47 initial items. Participants were invited to suggest additional items to include during the first round. Anonymous feedback was provided to inform each subsequent round of voting to encourage consensus. RESULTS: The eDelphi process established a CDS of 48 items recommended for inclusion in all HS registries globally. CONCLUSIONS: The routine adoption of this CDS in current and future HS registries should allow registries in different parts of the world to collaborate, enabling research requiring large numbers of participants.

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Breast cancer is the most common invasive malignancy in the world, with millions of survivors living today. Type 2 diabetes mellitus (T2DM) is also a globally prevalent disease that is a widely studied risk factor for breast cancer. Most breast tumours express the oestrogen receptor and are treated with systemic therapies designed to disrupt oestrogen-dependent signalling. Since the advent of targeted endocrine therapy six decades ago, the mortality from breast cancer has steadily declined; however, during the past decade, an elevated risk of T2DM after breast cancer treatment has been reported, particularly for those who received endocrine therapy. In this Review, we highlight key events in the history of endocrine therapies, beginning with the development of tamoxifen. We also summarize the sequence of reported adverse metabolic effects, which include dyslipidaemia, hepatic steatosis and impaired glucose tolerance. We discuss the limitations of determining a causal role for breast cancer treatments in T2DM development from epidemiological data and describe informative preclinical studies that suggest complex mechanisms through which endocrine therapy might drive T2DM risk and progression. We also reinforce the life-saving benefits of endocrine therapy and highlight the need for better predictive biomarkers of T2DM risk and preventive strategies for the growing population of breast cancer survivors.

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Background The human experience involves the inevitable end of life, whether sudden or expected. Ensuring a dignified end-of-life encounter necessitates understanding influential factors. Cardiomyopathy, a group of heart muscle diseases, has varying mortality implications, including heart failure and arrhythmias. Disparities in place of death (hospital, home, or hospice) can significantly alter the end-of-life care for a patient. Methods The aim of this study is to identify variations in death locations for U.S. cardiomyopathy patients between 1999 and 2020, based on age, gender, race, and census region, utilizing the CDC WONDER ( CDC Wide-Ranging Online Data for Epidemiologic Research) database, which contains a wide array of public health information. Data were categorized by age, gender, race, and location, and further subcategorized according to place of death. Statistical analysis was done via R programming software. Result The aggregate data of 528,401 cardiomyopathy-related deaths from 1990 to 2020 were obtained. Findings revealed age, gender, and regional disparities in death location. Notably, cardiomyopathy is found to be prevalent in the 75+ years age group, male gender, and people belonging to Caucasian descent, and maximal in the Southern census area. The study's logistic regression analysis unveiled a significant association between demographic factors and death locations. Conclusion This research underscores the significance of understanding disparities in the place of death for cardiomyopathy patients, shedding light on demographic influences and paving the way for patient-centered end-of-life care approaches.

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We characterized virus-neutralization and spike-binding antibody profiles in myeloma patients following monovalent or bivalent-SARS-CoV-2 booster vaccination. Vaccination improves the breadth of binding antibodies but not neutralization activity against current variants. Hybrid immunity and immune imprinting impact vaccine-elicited immunity.

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We characterized virus-neutralization and spike-binding antibody profiles in myeloma patients following monovalent or bivalent-SARS-CoV-2 booster vaccination. Vaccination improves the breadth of binding antibodies but not neutralization activity against current variants. Hybrid immunity and immune imprinting impact vaccine-elicited immunity.

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BACKGROUND: Obesity increases breast cancer risk and breast cancer-specific mortality, particularly for people with estrogen receptor (ER)-positive tumors. Body mass index (BMI) is used to define obesity, but it may not be the best predictor of breast cancer risk or prognosis on an individual level. Adult weight gain is an independent indicator of breast cancer risk. Our previous work described a murine model of obesity, ER-positive breast cancer, and weight gain and identified fibroblast growth factor receptor (FGFR) as a potential driver of tumor progression. During adipose tissue expansion, the FGF1 ligand is produced by hypertrophic adipocytes as a stimulus to stromal preadipocytes that proliferate and differentiate to provide additional lipid storage capacity. In breast adipose tissue, FGF1 production may stimulate cancer cell proliferation and tumor progression. METHODS: We explored the effects of FGF1 on ER-positive endocrine-sensitive and resistant breast cancer and compared that to the effects of the canonical ER ligand, estradiol. We used untargeted proteomics, specific immunoblot assays, gene expression profiling, and functional metabolic assessments of breast cancer cells. The results were validated in tumors from obese mice and breast cancer datasets from women with obesity. RESULTS: FGF1 stimulated ER phosphorylation independently of estradiol in cells that grow in obese female mice after estrogen deprivation treatment. Phospho- and total proteomic, genomic, and functional analyses of endocrine-sensitive and resistant breast cancer cells show that FGF1 promoted a cellular phenotype characterized by glycolytic metabolism. In endocrine-sensitive but not endocrine-resistant breast cancer cells, mitochondrial metabolism was also regulated by FGF1. Comparison of gene expression profiles indicated that tumors from women with obesity shared hallmarks with endocrine-resistant breast cancer cells. CONCLUSIONS: Collectively, our data suggest that one mechanism by which obesity and weight gain promote breast cancer progression is through estrogen-independent ER activation and cancer cell metabolic reprogramming, partly driven by FGF/FGFR. The first-line treatment for many patients with ER-positive breast cancer is inhibition of estrogen synthesis using aromatase inhibitors. In women with obesity who are experiencing weight gain, locally produced FGF1 may activate ER to promote cancer cell metabolic reprogramming and tumor progression independently of estrogen.

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Entry of antigen-specific T cells into human tumors is critical for immunotherapy, but the underlying mechanisms are poorly understood. Here, we combined high-dimensional spatial analyses with in vitro and in vivo modeling to study the mechanisms underlying immune infiltration in human multiple myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS). Clustered tumor growth was a feature of MM but not MGUS biopsies, and this growth pattern was reproduced in humanized mouse models. MM biopsies exhibited intralesional as well as spatial heterogeneity, with coexistence of T cell-rich and T cell-sparse regions and the presence of areas of T cell exclusion. In vitro studies demonstrated that T cell entry into MM clusters was regulated by agonistic signals and CD2-CD58 interactions. Upon adoptive transfer, antigen-specific T cells localized to the tumor site but required in situ DC-mediated antigen presentation for tumor entry. C-type lectin domain family 9 member A-positive (CLEC9A+) DCs appeared to mark portals of entry for gradients of T cell infiltration in MM biopsies, and their proximity to T cell factor 1-positive (TCF1+) T cells correlated with disease state and risk status. These data illustrate a role for tumor-associated DCs and in situ activation in promoting the infiltration of antigen-specific T cells in MM and provide insights into spatial alterations in tumor/immune cells with malignant evolution.

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