Factors determining utilization of stem cell transplant for initial therapy of multiple myeloma by patient race: exploring intra-racial healthcare disparities.

Multiple myeloma (MM) therapeutics have evolved tremendously in recent years, with significant improvement in patient outcomes. As newer treatment options are developed, stem cell transplant (SCT) remains an important modality that provides excellent disease control and delays the progression of disease. Over the years, SCT use has increased overall in the U.S., but two distinct gaps remain, including suboptimal use overall and racial-ethnic disparities. We evaluated the National Cancer Database (NCDB) to study what sociodemographic factors might play a role within a given racial-ethnic group leading to disparate SCT utilization, such that targeted approaches can be developed to optimize SCT use for all. In nearly 112,000 cases belonging to mutually exclusive categories of non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), Hispanics, non-Hispanic Asians (NHA), and others, we found certain factors including age, comorbidity index, payor type, facility type (academic vs. community) and facility volume to be uniformly associated with SCT use for all the racial-ethnic groups, while gender was not significant for any of the groups. There were several other factors that had a differential impact on SCT utilization among the various race-ethnicity groups studied, including year of diagnosis (significant for NHW, NHB, and Hispanics), income level (significant for NHW and Hispanics), literacy level (significant for NHW and NHB), and geographic location of the treatment facility (significant for NHW and NHA). The suboptimal SCT utilization overall in the U.S. suggests that there may be room for improvement for all, even including the majority NHW, while we continue to work on factors that lead to disparities for the traditionally underserved populations. This study helps identify sociodemographic factors that may play a role specifically in each group and paves the way to devise targeted solutions such that resource utilization and impact can be maximized.

Vena cava replacement and major hepatectomy for liver tumors: international multicenter retrospective cohort study.

INTRODUCTION: Involvement of the inferior vena cava (IVC) and hepatic veins (HV) has been considered a relative contraindication to hepatic resection for primary and metastatic liver tumors. However, patients affected by tumors extending to the IVC have limited therapeutic options and suffer worsening of quality of life due to IVC compression. METHODS: Cases of primary and metastatic liver tumors with vena cava infiltration from 10 international centers were collected (7 European, 1 US, 2 Brazilian, 1 Indian) were collected. Inclusion criteria for the study were major liver resection with concomitant vena cava replacement. Clinical data and short-term outcomes were analyzed. RESULTS: 36 cases were finally included in the study. Median tumor max size was 98 mm (range: 25-250). A biliary reconstruction was necessary in 28% of cases, while a vascular reconstruction other than vena cava in 34% of cases. Median operative time was 462 min (range: 230-750), with 750 median ml of estimated blood loss and a median of one pRBC transfused intraoperatively (range: 0-27). Median ICU stay was 4 days (range: 1-30) with overall in-hospital stay of 15 days (range: 3-46), post-operative CCI score of 20.9 (range: 0-100), 12% incidence of PHLF grade B-C. Five patients died in a 90-days interval from surgery, 1 due to heart failure, 1 due to septic shock and 3 due to multiorgan failure. With a median follow-up of 17 months (interquartile range: 11-37), the estimated five-years overall survival was 48% (95% CI: 27%-66%), and five-year cumulative incidence of tumor recurrence was 55% (95% CI: 33%-73%). CONCLUSIONS: Major liver resections with vena cava replacement can be performed with satisfactory results in expert HPB centers. This surgical strategy represents a feasible alternative for otherwise unresectable lesions and is associated with favorable prognosis compared to non-operative management, especially in patients affected by intrahepatic cholangiocarcinoma.

A phase II study of ibrutinib in combination with ixazomib in patients with Waldenström macroglobulinaemia.

This phase II study evaluated time-limited (24 cycles) treatment with ibrutinib and ixazomib in newly diagnosed (NDWM; n = 9) and relapsed/refractory (RRWM; n = 12) Waldenström macroglobulinaemia (WM). The overall response rate (ORR) was 76.2% (n = 16) in 21 evaluable patients with no patient achieving a complete response (CR). The median duration of treatment was 15.6 months, and after a median follow-up time of 25.7 months, the median progression-free survival (PFS) was 22.9 months. While the primary end-point was not met (CR rate at any time) and 28.5% discontinued treatment due to toxicity, ibrutinib plus ixazomib led to a clinically meaningful ORR and PFS. Combined Bruton's tyrosine kinase (BTK) and proteasome inhibition merits further evaluation in WM.

Acquired Factor VII Deficiency Associated With Chronic Myeloid Leukemia Blast Crisis.

Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.

Anti-B Cell Maturation Antigen Chimeric Antigen Receptor T Cell Therapy for the Treatment of AL Amyloidosis and Concurrent Relapsed/Refractory Multiple Myeloma: Preliminary Efficacy and Safety.

While immunotherapies, such as CAR T therapy and bi-specific antibodies, have revolutionized the treatment of multiple myeloma (MM), patients with AL amyloidosis have been excluded from trials with these agents due to concerns of underlying autonomic, cardiac, and renal dysfunction, leading to potentially fatal toxicities from these therapies. In this communication, we described the outcomes of two patients with AL amyloidosis and concurrent MM with underlying cardiac and/or renal dysfunction who underwent anti-BCMA CAR T cell therapy with ide-cel or cilta-cel, received cytokine release syndrome prophylaxis, and tolerated therapy well with manageable toxicities and achieved a MRD-negative state. We described the preliminary efficacy and safety of CAR T in patients with AL amyloidosis and highlighted the importance of patient selection and medical optimization of cardiac and renal function prior to CAR T.

The digital divide: Racial disparities in adoption and utilization of health information technology among patients with lymphoid cancers.

INTRODUCTION: Health information technology (HIT) has the potential to improve healthcare delivery and engagement. Studying racial-ethnic disparities in HIT engagement will help understand and overcome challenges to healthcare utilization. METHODS: We undertook a patient-reported survey among patients with lymphoid malignancies at two campuses of Mayo Clinic, Florida to explore HIT-related disparities. Variables between Whites and non-Whites, and non-Whites from the two campuses were compared. RESULTS: The survey was completed by 1004 respondents, with 71% whites, 27% non-Whites (race-ethnicity not reported by 2%). Non-Whites included 30% responders at the main campus and 64% at an inner-city campus. Whites were significantly older and had higher education, while non-Whites had lesser access to a computer. Only 51% of non-Whites were registered to use electronic medical records (EMR) as compared to 72% Whites (p < 0.001) and significantly lesser number of non-Whites even knew that EMR existed (81% vs. 92%, p < 0.001). Encouragingly, a higher number of non-Whites wanted to engage in EMR. Non-Whites from the main campus were older, more educated and had more access to a computer as compared to those from the inner-city campus. Similar disparate factors were noted among minorities from the two campuses, suggesting impact of socioeconomic backgrounds on EMR usage among non-Whites. Linguistic barriers were more striking among inner-city campus non-Whites. CONCLUSIONS: Non-Whites continue to struggle with suboptimal utilization of the healthcare system and barriers related to integration in HIT, including disparities representing socioeconomic differences. Efforts need to be made at several levels to help racial-ethnic minorities overcome awareness, access, and linguistic barriers to HIT utilization.

Omission of day +11 methotrexate dose and allogeneic hematopoietic cell transplantation outcomes: results of a systematic review/meta-analysis.

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for patients with malignant and benign hematologic conditions. Graft-versus-host disease (GVHD) is a known complication of allo-HCT that results in significant morbidity and mortality. A common GVHD prophylaxis strategy combines a calcineurin inhibitor with methotrexate. When mucositis and organ toxicity develop, the day +11 dose is frequently omitted to limit further organ damage. The potential impact of this practice on allo-HCT outcomes is unclear as published data show conflicting results. Thus, we performed a systematic review/meta-analysis of the available literature to assess the impact of omitting day +11 methotrexate on allo-HCT recipients. Data were extracted in relation to benefits (overall survival [OS], progression-free survival [PFS]) and harms (acute and chronic GVHD, non-relapse mortality [NRM], and relapse). Pooled OS rate favored those who received day +11 methotrexate vs. those who did not (HR = 1.21; 95% CI = 1.02-1.43; p = 0.03). There was no significant difference in pooled rates of PFS (HR = 0.96; 95% CI = 0.60-1.52; p = 0.85), acute GVHD (HR = 1.03; 95% CI = 0.35-2.98; p = 0.96), chronic GVHD (HR = 0.83; 95% CI = 0.44-1.57; p = 0.57), NRM (HR = 0.86; 95% CI = 0.67-1.11; p = 0.25), and relapse (HR = 0.97; 95% CI = 0.75-1.26; p = 0.83) between the two groups. Large prospective multicenter studies are needed to better define the significance of day +11 methotrexate omission.

Urinary CXCL10 specifically relates to HLA-DQ eplet mismatch load in kidney transplant recipients.

BACKGROUND: Urinary CXCL10 (uCXCL10) is associated with graft inflammation and graft survival, but the factors related to its excretion are not well known. HLA molecular matching at epitope level allow estimating the "dissimilarity" between donor and recipient HLA more precisely, being better related to further transplant outcomes. The relationship between uCXCL10 and HLA molecular mismatch has not been previously explored. METHODS: HLA class I and class II typing of some 65 recipients and their donors was retrospectively performed by high resolution sequence-specific-primer (Life Technologies, Brown Deer, WI). The HLA-Matchmaker 3.1 software was used to assess eplet matching. Urine samples collected on the day of the 1-year surveillance biopsy were available of these 65 patients. uCXCL10 was measured using a commercial enzyme-linked immunoassay kit. RESULTS: 1-year uCXCL10 was independently associated with HLA-DQB1 eplet mismatch load (ß 0.300, 95%CI 0.010-0.058, p = 0.006). Kidney transplant recipients with a HLA-DQB1 eplet mismatch load >3 showed higher values of uCXCL10 at 1-year (p = 0.018) than those with ≤3. Patients with a HLA-DQB1 eplet mismatch load >3 with subclinical AbMR had significantly higher levels of the logarithm of 1-year uCXCL10 (No AbMR 0.88, IQR 0.37; AbMR 1.38, IQR 0.34, p = 0.002) than those without AbMR. CONCLUSIONS: uCXCL10 specifically relates to HLA-DQ eplet mismatch load. This relationship can partly explain the previously reported association between uCXCL10 excretion and graft inflammation. An adequate evaluation of any potential non-invasive biomarker, such as uCXCL10, must take into account the HLA molecular mismatch.

Review: Ischemia Reperfusion Injury-A Translational Perspective in Organ Transplantation.

Thanks to the development of new, more potent and selective immunosuppressive drugs together with advances in surgical techniques, organ transplantation has emerged from an experimental surgery over fifty years ago to being the treatment of choice for many end-stage organ diseases, with over 139,000 organ transplants performed worldwide in 2019. Inherent to the transplantation procedure is the fact that the donor organ is subjected to blood flow cessation and ischemia during harvesting, which is followed by preservation and reperfusion of the organ once transplanted into the recipient. Consequently, ischemia/reperfusion induces a significant injury to the graft with activation of the immune response in the recipient and deleterious effect on the graft. The purpose of this review is to discuss and shed new light on the pathways involved in ischemia/reperfusion injury (IRI) that act at different stages during the donation process, surgery, and immediate post-transplant period. Here, we present strategies that combine various treatments targeted at different mechanistic pathways during several time points to prevent graft loss secondary to the inflammation caused by IRI.

Gender differences in ST-elevation myocardial infarction (STEMI) time delays: experience of a public health service in Salvador-Brazil.

BACKGROUND: Delays in attending to ST-elevation myocardial infarction (STEMI) are indicators or markers of quality of health services. Several records suggest gender disparity in cardiac care as a contributor to the increased mortality among women. METHODS: We prospectively enrolled all consecutive STEMI patients who were transferred to our hospital from January through December 2015. The following variables were analyzed: Symptom-to-Door Time (SDT); Time to First ECG (TECG); Transfer Time to Referring Center (TTRC); and Door-to-Cath lab time (DCT). RESULTS: Of the 133 patients, 85 (63.9%) were male and 45 (36%) female. The mean age and body mass index (BMI) between the male and female genders were 56.3 and 60.5 years for the first and 26 and 27.7 Kg/M2 for the second. Diabetes and low school education level were more prevalent in women than men, with statistical significance: 20 (48.8%) vs 18 (26.1%) with P = 0.01 and 26 (54.2%) vs 28 (32.9%) with P = 0.04, respectively. Regarding the times evaluated (SDT, TECG, TTRC and DCT), there was no statistically significant difference in relation to gender. STEMI Killip class I was more prevalent in males: 93 (86.1%) vs 12 (63.2%) cases with P = 0.01, and thrombolysis with a tendency towards the same direction: 17 (20%) vs 4 (8.3%) and P = 0.07. CONCLUSIONS: According to our results women with STEMI had significantly higher prevalence of diabetes and low school education level, as well as a higher proportion of complicated STEMI (Killip class ≥ II).

Interspecific variation in the repair of UV damaged DNA in the genus Xiphophorus as a factor in the decline of the Rio Grande Platyfish.

The fish genus Xiphophorus consists of 26 species distributed along the eastern slopes of mountain ranges extending from northern Mexico to Belize and Nicaragua. We analyzed light-dependent repair of UV-induced DNA damage in at least two species from each of the four monophyletic Xiphophorus groups. We found that the northern platyfish had significantly reduced photoenzymatic repair compared to the other three groups, including the northern swordtails, southern platyfish and southern swordtails. All of the species of the northern platyfish, including the Marbled (meyeri), Northern (gordoni) and Monterrey Platyfish (couchianus) are the northernmost species in the genus and are the only three species in the genus that are currently found on the IUCN Red List of Threatened Species. Satellite data from the past 30 years (1979-2008) correlate greater increases in shorter wavelength UVB with higher latitudes within the Xiphophorus range. We suggest that, combined with other consequences of human population growth, anthropogenic deozonation resulting in a disproportionate increase in UVB in temperate latitudes may be a contributing factor in the decline and extirpation of the northern platyfish.

Acute exposure to ultraviolet-B radiation modulates sex steroid hormones and receptor expression in the skin and may contribute to the sex bias of melanoma in a fish model.

Using the Xiphophorus fish melanoma model, we show a strong male bias for sunlight-induced malignant melanoma, consistent with that seen in the human population. To examine underlying factors, we exposed adult X. couchianus fish to a single, sublethal dose of UVB and measured circulating sex steroid hormones and expression of associated hormone receptor genes over a 24-h period. We found that a single exposure had profound effects on circulating levels of steroid hormones with significant decreases for all free sex steroids at 6 and 24 h and increases in conjugated 2-estradiol and 11-ketotestosterone at 6 and 24 h, respectively. Whereas ARα expression increased in male and female skin, neither ARß nor either of the ERs showed significant responses to UVB in either sex. The rapid response of male androgens and their receptors in the skin after UVB irradiation implicates hormones in the male bias of skin cancer and suggests that the photoendocrine response immediately after UV exposure may be relevant to melanomagenesis.

Recent advances in sunlight-induced carcinogenesis using the Xiphophorus melanoma model.

Unlike breast and prostate cancers, the nature and sequence of critical genetic and epigenetic events involved in the initiation and progression of melanoma are not well understood. A contributing factor to this dilemma, especially given our current understanding of the importance of UV light in melanoma etiology, is the lack of quality UV-inducible melanoma animal models. In this study we elaborate on the capability of UV light to induce cutaneous malignant melanomas (CMM) in Xiphophorus fishes, which were previously found to develop melanomas after acute neonatal UVB irradiation. In two separate tumorigenesis experiments, we exposed adult Xiphophorus hybrids to either acute UVB irradiations (5 consecutive daily treatments) or chronic solar irradiations (continuous UVA/UVB treatment for 9 months). Acute adult UVB irradiation resulted in the significant induction of melanomas, and moreover, this induction rate is equivalent to that of animals exposed to acute neonatal UVB irradiation. This study represents the first evidence that acute adult UVB irradiation, in the absence of any early life exposures, induces CMM. Similar to the findings conducted on other divergent melanoma models, including HGF/SF transgenic mice and Monodelphis domestica, prolonged chronic solar UV was not a factor in melanomagenesis.

The photobiology of melanocytes modulates the impact of UVA on sunlight-induced melanoma.

Ultraviolet radiation is responsible for melanoma. In this review, we address the role of the different UV spectra in melanoma. The data suggest that only UVB is capable of initiating melanoma, and that both UVA and UVB are involved in the progression of the disease. The etiology of sunlight-induced melanoma may be different for chronically-exposed tumors and for those located on body surfaces with considerably less exposure. Solar signature mutations are most likely associated with the progression of chronically-exposed tumors. The unique relationship between UVA and melanocytes, and the role of melanin in photocarcinogenesis is discussed. The current state of knowledge strongly indicates that UVA, regardless of its source, is involved in melanoma and should be avoided to deter progression of incipient tumors.

An experimental population study of nucleotide excision repair as a risk factor for UVB-induced melanoma.

Nucleotide excision repair (NER) is the primary defense against the DNA damage implicit in skin cancer formation and is negatively affected by chronic exposure to UVB radiation. However, in situ and in vitro studies consistently yield equivocal results when addressing individual DNA repair capacity and melanoma susceptibility. The primary objective of this study was to determine if individual global NER capacity is a risk factor for melanoma formation in a prominent UVB-inducible melanoma model, hybrid Xiphophorus fishes. After neonatal UVB irradiation, adult tumor-bearing and tumor-free fish were given a challenge UVB dose and (6-4) photoproduct repair was quantified in individual fish at 24 h using radioimmunoassay. Despite considerable inter-individual variation in repair capacity, ranging from 13% to 91%, we found no difference in mean NER capacity between fish with and without melanomas, thus detaching global NER from melanomagenesis. Furthermore, despite epidemiological data indicating that sex and age are important risk factors underlying melanoma susceptibility, we found no difference in mean NER rates among the sexes or as a function of age. We conclude with a discussion of the apparent paradox of how inter-individual variation in NER is not a risk factor given the clear evidence that DNA damage underlies melanoma susceptibility.

Selection for a dominant oncogene and large male size as a risk factor for melanoma in the Xiphophorus animal model.

Adult height is a risk factor in numerous human cancers that involve aberrant receptor tyrosine kinase (RTK) signalling. However, its importance is debated due to conflicting epidemiological studies and the lack of useful in vivo models. In Xiphophorus fishes (Platyfishes/Swordtails), a functional RTK, Xiphophorus melanoma receptor kinase (Xmrk), serves as the dominant oncogene and has been maintained for several million years despite being deleterious and in an extremely unstable genomic region. Here we show that the Xmrk genotype is positively correlated with standard length in male and female wild caught Xiphophorus cortezi sampled throughout their phylogeographic distribution. Histopathology confirms the occurrence of malignant melanomas in both sexes; however, melanoma incidence was extremely male biased. Furthermore, males collected with malignant melanomas in the field were significantly larger than both Xmrk males collected without melanomas and wildtype (Xmrk deficient) males. These results not only provide a novel selective mechanism for the persistence of the germline Xmrk oncogene but also create an innovative avenue of melanoma research within the Xiphophorus fishes. Wildlife cancer in natural systems is a growing concern, therefore, future research investigating life history characteristics associated with certain phenotypes and genotypes that predispose an individual to cancer will be fundamental to increasing our understanding of the evolutionary biology of cancer in nature as well as in humans.

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model.

We examined the wavelength dependence of ultraviolet (UV) ra-diation (UVR)-induced melanoma in a Xiphophorus backcross hybrid model previously reported to be susceptible to melanoma induction by ultraviolet A (UVA) and visible light. Whereas ultraviolet B (UVB) irradiation of neonates yielded high frequencies of melanomas in pigmented fish, UVA irradiation resulted in melanoma frequencies that were not significantly different from unirradiated fish. Spontaneous and UV-induced melanoma frequencies correlated with the degree of pigmentation as expected from previous studies, and the histopathology phenotypes of the melanomas were not found in significantly different proportions in UV-treated and -untreated tumor-bearing fish. Our results support the conclusion that a brief early-life exposure to UVB radiation causes melanoma formation in this animal model. These data are consistent with an essential role for direct DNA damage, including cyclobutane dimers and (6-4) photoproducts, in the etiology of melanoma.

Pericondrite pós-piercing / Post-piercing perichondritis

O uso de piercing tem se tornado uma prática muito freqüente entre os jovens. O procedimento na maioria vezes realizado por profissionais não-qualificados não é isento de riscos. O manuseio de material contaminado ou a higiene imprópria predispõem à pericondrite e à celulite. A pericondrite caracteriza-se pelo eritema do pavilhão auricular, dor intensa e febre. Sem tratamento, desenvolve-se um edema generalizado do pavilhão com formação de abscesso subpericondrial, podendo evoluir para necrose isquêmica da cartilagem e a temível deformidade estética conhecida como "orelha em couve flor". O agente responsável mais encontrado é o Pseudomonas aeruginosa. No estágio inicial da doença o tratamento pode ser feito com antibióticos de amplo espectro. Nos casos em que o abscesso está presente, a incisão e drenagem cirúrgica são obrigatórios acompanhado de antibioticoterapia guiado pela cultura e antibiograma. OBJETIVO: O objetivo deste relato de caso é realizar uma revisão bibliográfica dos últimos 10 anos abordando os aspectos anatômicos do pavilhão auricular, a história do uso de piercing e suas mais conhecidas complicações. MÉTODO: Relato de um caso de pericondrite pós-piercing transcartilaginoso onde houve a necessidade de tratamento cirúrgico com praticamente nenhuma deformidade estética. RESULTADO: Aquisição de experiência teórico-prática através de revisão bibliográfica e relato de um caso de evolução favorável para a paciente. CONCLUSÃO: Incidência crescente das complicações de pericondrites na população jovem deve levar à prevenção primária mais elaborada.

Piercing has become more and more popular among adolescents. The procedure is generally performed by unqualified professionals and carries its risk. Non-sterilized material or inappropiate hygiene increases the possibility of perichondritis and celulitis. The disease is characterized by erythema of the auricula pinna, unbearable pain and fever. Left untreated, the condition progresses with edema along the auricula and abscess formation that may result in ischemic necrosis and a cauliflower anesthetic deformation. The most common bacteria is Pseudomonas aeruginosa. In cases with abscesses, drainage is necessary along with antibiotic therapy guided by cultures and antibiogram. AIM: The aim of this case report was to review the past 10 years of published papers dealing with anatomical aspects of the auricular pinna, the history of piercing and its most common complications. METHODS: A case report of perichondritis after "high" ear piercing that required surgical treatment and that progressed with no esthetic loss. RESULTS: Theoretical and practical experience based on a review and a report of a case that progressed satisfactorily. CONCLUSIONS: The increased incidence of perichondritis in adolescents should require more elaborated primary prevention measures.

Mate choice for more melanin as a mechanism to maintain a functional oncogene.

The mechanisms by which cancer evolves and persists in natural systems have been difficult to ascertain. In the Xiphophorus melanoma model, a functional oncogene (Xiphophorus melanoma receptor kinase Xmrk) has been maintained for several million years despite being deleterious and in an extremely unstable genomic region. Melanomas in Xiphophorus spp. fishes (platyfishes and swordtails) have been investigated since the 1920s, and, yet, positive selection that could explain the maintenance of Xmrk has not been found. Here, we show that Xiphophorus cortezi females from two populations prefer males with the spotted caudal (Sc) melanin pattern, which is associated with the presence of the Xmrk oncogene and serves as the site of melanoma formation within this species. Moreover, X. cortezi females prefer males with an enhanced Sc to males with a reduced Sc pattern. RT-PCR analysis confirms tissue-specific Xmrk expression within the Sc pattern in X. cortezi. Because of the association of Xmrk with the Sc pigment pattern and the fact that melanoma formation augments this visual signal, sexual selection appears to be maintaining this oncogene because of a mating preference for Sc, as well as the exaggeration of this male trait. At the individual level, decreases in viability and fecundity because of Xmrk and subsequent melanoma formation may be mitigated via increases in mate acquisition. At the population level, maintenance of this oncogene appears to be under frequency dependent selection, as we detected female preference for males without Sc in a third population that had higher frequencies of Sc in females.