Treatment of refractory Hodgkin's lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody.

PURPOSE: Hodgkin's lymphoma (HL) has been demonstrated to be a good target for immunotherapy since lymphocyte activation markers such as CD30 are expressed in high numbers on the malignant cells. Thus, we developed a new radioimmunoconjugate consisting of the murine anti-CD30 monoclonal antibody (MAb) Ki-4 labeled with iodine-131 ((131)I). PATIENTS AND METHODS: The biodistribution of (131)I-Ki-4 was assessed via dosimetry after preinfusion of 5 mg native Ki-4 followed by 250 to 300 MBq (131)I-labeled Ki-4. Whole-body scintigraphy was performed 1 hour, 24 hours, 48 hours, 72 hours, and 6 days after the infusion. Dosimetry was calculated using the programs NucliDose ICON-IDL (version 5.0.2; Siemens, Erlanger, Germany) and MIRDOSE (version 3.1; Oak Ridge National Laboratories; Oak Ridge, TN). The therapeutic dose was given on day 8 after preinfusion of unlabeled Ki-4. RESULTS: We treated 22 patients with relapsed or refractory CD30-positive HL. Preinfusion of 5 mg native Ki-4 was sufficient to bind the soluble CD30. Imaging demonstrated localization of involved areas measuring 5 cm in diameter or more in four patients and 2.5 cm in one patient. Patients received total body doses of 0.035 Gy to 0.99 Gy. Acute toxicity was mild with grade 1 fatigue in 19 of 22 assessable patients. Seven patients experienced grade 4 degrees hematotoxicity 4 to 8 weeks after treatment. Response included one complete remission, five partial remissions, and three minor responses. CONCLUSION: Treatment with (131)I-Ki-4 is effective but can be associated with severe hematotoxicity.     

Phase II study of oxaliplatin for treatment of patients with mucosa-associated lymphoid tissue lymphoma.

PURPOSE: Various chemotherapeutic regimens have been applied for treatment of mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard regimen has been identified to date. In view of the activity of oxaliplatin (L-OHP) in various types of lymphoma, we performed a phase II study to evaluate the activity of L-OHP for treatment of MALT lymphoma. The primary objective of this study was to determine the objective response rate according to WHO standard criteria. PATIENTS AND METHODS: A total of 16 patients with MALT lymphoma of various sites of origin (four of the ocular adnexa, five of the salivary glands, three of the stomach, two of the lung, and one of the colon and the breast) were administered L-OHP at a dose of 130 mg/m2 infused during 2 hours every 3 weeks. Restaging was performed every two cycles; treatment was continued until complete remission (CR) or for a maximum of six cycles in responders. RESULTS: Sixty-five cycles were administered (median, four; range, two to six); toxicity consisted of transient sensory neuropathy in eight patients and nausea/emesis WHO grade 2 in two patients, whereas hematologic adverse effects (thrombocytopenia and leukocytopenia grade 2) occurred in only one patient each. Fifteen patients responded to chemotherapy, with nine achieving CR (56%), six (37.5%) achieving partial response, and one achieving stable disease; the median time to response was 4 months (range; 2 to 4 months). CONCLUSION: These data suggest L-OHP is a highly active agent for treatment of MALT lymphoma. However, a longer follow-up is needed to judge whether these remissions are durable.     

Measurement of aggregate risk with copulas

Summary When aggregating financial risk on a portfolio level, the specification of the dependence structure between the risk factors plays an important role. Promising parametric models are often based on a so-called copula approach. Case studies of market crashes suggest the application of concepts allowing for extremal dependence. We present a transformed copula as a new model that both fits the data and allows for exact prediction in the tails. It turns out that the new model improves benchmark models like the t- or Clayton copula with respect to risk measures like VaR or Expected Shortfall. By performing different goodness-of-fit tests, the quality of the estimation is examined.     

Predictors associated with mortality of extracorporeal life support therapy for acute heart failure: single-center experience with 679 patients

BackgroundExtracorporeal life support (ECLS) therapy is increasingly used for cardiac and respiratory support postcardiotomy, refractory cardiogenic shock and cardiopulmonary resuscitation. This study aims to describe in-hospital mortality of patients requiring ECLS, identify independent predictors associated with mortality and analyze changes of mortality over time.MethodsThis retrospective study includes all adult ECLS cases at the University Hospital Zurich, a designated ECLS center in Switzerland, in the period 2007 to 2019.ResultsECLS therapy was required in 679 patients (median age 60 years, 27.5% female). In-hospital mortality was 55.5%. Cubic spline interpolation did not detect evidence for a change in mortality over the whole period of 13 years. In-hospital mortality significantly varied between ECLS indications: 70.7% (152/215) for postcardiotomy, 67.9% (108/159) for cardiopulmonary resuscitation, 47.0% (110/234) for refractory cardiogenic shock, and 9.9% (7/71) for lung transplantation and expansive thoracic surgery (P<0.001). Logistic regression modelling showed excellent discrimination in the receiver operating characteristic (ROC) area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87–0.92] and identified significant mortality predictors: age, simplified acute physiology score (SAPS) II, as well as new liver failure and each allogenic blood transfusion unit given per day. ECLS after cardiopulmonary resuscitation was associated with significantly higher mortality compared to ECLS for refractory cardiogenic shock.ConclusionsIn-hospital mortality of patients treated with ECLS therapy is high. Outcomes have not changed significantly in the observed period. We identified age, SAPS II, new liver failure and each allogenic blood transfusion unit given per day as independent mortality predictors. Knowledge of predictors strongly associated with in-hospital mortality may affect future decisions about ECLS indications and the respective management to use this elaborate therapy more effectively.     

White patients’ physical responses to healthcare treatments are influenced by provider race and gender

The healthcare workforce in the United States is becoming increasingly diverse, gradually shifting society away from the historical overrepresentation of White men among physicians. However, given the long-standing underrepresentation of people of color and women in the medical field, patients may still associate the concept of doctors with White men and may be physiologically less responsive to treatment administered by providers from other backgrounds. To investigate this, we varied the race and gender of the provider from which White patients received identical treatment for allergic reactions and measured patients’ improvement in response to this treatment, thus isolating how a provider’s demographic characteristics shape physical responses to healthcare. A total of 187 White patients experiencing a laboratory-induced allergic reaction interacted with a healthcare provider who applied a treatment cream and told them it would relieve their allergic reaction. Unbeknownst to the patients, the cream was inert (an unscented lotion) and interactions were completely standardized except for the provider’s race and gender. Patients were randomly assigned to interact with a provider who was a man or a woman and Asian, Black, or White. A fully blinded research assistant measured the change in the size of patients’ allergic reaction after cream administration. Results indicated that White patients showed a weaker response to the standardized treatment over time when it was administered by women or Black providers. We explore several potential explanations for these varied physiological treatment responses and discuss the implications of problematic race and gender dynamics that can endure “under the skin,” even for those who aim to be bias free.

The face of medicine is changing. Women and people of color make up an increasing percentage of health care providers (1–3). In 2017, for the first time in history, women were the majority of accepted medical school applicants in the United States and the number of non-White accepted applicants rose to above 50%. Here, we ask whether this recent demographic shift in the race and gender of doctors is also shifting long-held, societally pervasive notions of what a doctor “looks like.”Despite the increasing diversity of the medical field, for most people in most contexts, the association between “doctor” and “White man” is still likely strong and pervasive. This is hardly surprising. For most of medical history in North America, the majority of physicians fit this profile (see Fig. 1 A and B), and even now the majority of practicing physicians are still men and nearly half are White (see Fig. 1 C and D). Consequently, the emerging links between “Doctor and Woman” and between “Doctor and Black person,” for example, are likely weak. Moreover, to the extent that those associations exist, they are likely to have to compete for attention with an array of strong, frequent, and negative associations that undermine the links between women and competence and African Americans and competence (4–6).Open in a separate windowFig. 1.The change in the representation of women (A) and people color (B) in the number of accepted applicants to US medical schools, as well as the current representation of professionally active women physicians (C) and physicians of color (D). (A and B) From the Association of American Medical Colleges (AAMC). (C) From the Henry J. Kaiser Family Foundation. (D) From 2013 from the Association of American Medical Colleges (AAMC). AAMC data on race/ethnicity were not available for 2013 or 2014, hence explaining the gaps in the graph around these years in B.In patient–provider interactions, as in every social encounter, people bring with them a set of learned associations about social groups that have been formed by their various life experiences (e.g., personal interactions, media exposure) (6–12). Mirroring the historical representation of doctors in actual medical practice, representations of doctors in popular media have overwhelmingly been as White men (13–15). Patients who have learned this societally pervasive “Doctor = White man” association through their actual encounters with physicians as well as through movies, television, books, and advertising may respond less positively to care from Black and women providers. These associations may exist at an implicit level even in the context of positive explicit attitudes toward Black doctors and women doctors (16, 17), and they are potentially powerful, influencing the course of medical care. Also, while it is clear from past research that being a target of bias can be harmful to health (e.g., people who face race-based discrimination face adverse physical and mental health consequences) (18), it is unclear whether viewing another social group in light of societally pervasive associations (e.g., about doctors on the basis of gender and race) can be harmful to the health of the perceiver.Here, we focus on how the race and gender of doctors may impact patients’ responses to the expectations doctors set about medical treatment. Previous research shows that a provider’s expressed expectations for a medical treatment (i.e., that it will benefit patients) can improve patient engagement, adherence, and physiological responses to treatment (19–25). Based on these findings, we anticipate that patients who interact with a doctor whose personal characteristics (e.g., race, gender) do not conform to dominant societal representations of what a doctor looks like may be less responsive to such expectations. We hypothesize that patients may be less responsive to the exact same medical treatment when the doctor who sets expectations that this treatment will be beneficial is not a White man.This hypothesis draws on a large and growing body of research suggesting that the total effect of a healthcare treatment depends on the social context in which that treatment takes place (25–29). The realization that the social context can influence treatment and medical outcomes is bolstered by a large body of research on the placebo effect (26). Although people may sometimes assume that actual pharmaceutical properties of a medication or treatment are solely responsible for its total benefit, placebo paradigms show that the total effect of treatment is in fact a combined product of the drug and their medical properties (e.g., acetaminophen, antihistamines), the body’s natural healing abilities (e.g., endogenous opioids and antihistamines), and the psychological and social context (e.g., what a patient believes about treatment and the qualities of the person who administers the treatment) (SI Appendix, Fig. S1). For example, past research suggests that a physician’s characteristics, such as their projected warmth and competence, influences how much a patient improves in response to treatment. In one recent study (22), the researchers independently manipulated whether a provider acted more or less warm, and more or less competent, toward a patient during an allergy skin prick test that induced a mild allergic reaction. The provider set positive expectations about a placebo cream (i.e., unscented hand lotion) placed on the reaction, informing patients that this cream was an antihistamine that would reduce the reaction. When the provider was both warm and competent, patients showed a stronger physiological response to the placebo treatment over time; their allergic reaction decreased the most rapidly in size, in response to the positive expectations that the provider had set. Thus, aspects of social interactions with providers can influence the degree to which the positive expectations that a provider sets about treatment ultimately influence physiological treatment response.As in most social interactions in the United States, race and gender are likely salient aspects of the social context in patient–provider interactions (30, 31, 32). Previous research has found, for example, that patient race can influence the quality of care received from doctors in myriad ways (33–36). Here, we focus on provider race and provider gender as features of the social context that can influence patients’ response to treatment. Specifically, we ask the following: will White patients exhibit a weaker physiological response to the expectations set about treatment by doctors who are not White and men?     

Rhombohedral Phase Formation in Yttria-Stabilized Zirconia Induced by Dental Technical Tools and Its Impact on Dental Applications

In the study the influence of different dental technical tools on the surface temperature and phase composition of fixed dental prostheses (FDPs) made of yttria-partially stabilized zirconia polycrystals (3Y-/4Y-/5Y-PSZ) was investigated. FDPs were fabricated by using computer-aided manufacturing (CAM). The FDPs were treated with a contra-angle handpiece equipped with different burs and polishers. The resulting surface temperatures were measured with a thermographic camera, and the resulting phase transformations were investigated by X-ray diffraction and quantified by Rietveld refinement. Processing with burs resulted in no phase transformation, but a preferred orientation shift. Using coarse polisher induced a phase transformation to the rhombohedral phase, while fine polishers produced no relevant phase transformations and no preferred orientation shift. Compared to the monoclinic phase (ca. 9% theoretical volume increase), which is associated with low-temperature degradation (LTD), the rhombohedral phase is much more voluminous (ca. 15% theoretical volume increase) and distorted and, therefore, has a greater degradation potential.     

SARS-CoV-2 Specific Immune Response and Inflammatory Profile in Advanced HIV-Infected Persons during a COVID-19 Outbreak

The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1β, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay. Mann–Whitney or Kruskal–Wallis tests were used for comparisons. Thirty patients were included with the following demographics: age, 57 years old (IQR, 53–62); 76% male; median HIV duration of infection, 18 years (15–29); nadir of CD4, 57/mmc (23–100) current CD4 count, 348/mmc (186–565). Furthermore, 83% had at least one comorbidity. The severity of COVID-19 was mild/moderate, and the overall mortality rate was 10% (3/30). Additionally, 90% of patients showed positive antibody titers and neutralizing activity, with a 100% positive SARS-CoV-2 specific T-cell response over time, suggesting the ability to induce an effective specific immunity. Significantly higher levels of IL-6, IL-8, and TNF-α in COVID-19 without HIV vs. HIV/COVID-19 patients (p < 0.05) were observed. HIV infection did not seem to negatively impact COVID-19-related inflammatory state and immunity. Further data are mandatory to evaluate the persistence of these immunity and its ability to expand after exposure and/or vaccination.