An Institution "at Arm's Length" Gonzalez-Rivas, Rebecca
The University of Chicago law review,
09/2020, Letnik:
87, Številka:
6
Journal Article
Recenzirano
Grand jury proceedings are shrouded in secrecy. No judge presides over them, no reporter annotates them, and when they have concluded, no juror may speak about them. While secrecy serves many ...important functions for the grand jury, its veil may be lifted under certain circumstances. Grand jury records may be released if they fall under a disclosure exception laid out in Federal Rule of Criminal Procedure 6(e). While some courts limit release to the exceptions laid out in the Rule, others look to an alternative source of authority.
Several courts of appeals have held that district court judges may exercise inherent supervisory power in authorizing the release of grand jury records. Judges may consider the public interest in disclosure, compare it to the institutional interest in secrecy, and decide for themselves. Other circuits find no such power.
The circuits have reached an impasse on the text of the Rule alone, with each side offering compelling but incomplete justifications for their interpretation. This Comment provides an alternative path forward. By examining the history of the grand jury and the relationship between the Federal Rules and common law supervisory power, this Comment argues that district court judges lack inherent supervisory power over the grand jury to order disclosure. Courts that follow the exhaustive position—that Rule 6(e)(3) limits the exceptions when a court may authorize disclosure—better align with the understanding of the grand jury as an independent body. Conscious of this historical positioning, this Comment returns to both influential and overlooked Supreme Court precedent and offers a more contextually grounded interpretation of each. Judges have discretion to act within the bounds of Rule 6(e), not outside of it.
According to the interpersonal theory of suicide, the perception of imposing a burden on loved ones increases the risk for suicidal ideation. Little research, however, has examined the interaction of ...burdensomeness with cognitive variables in predicting suicidal ideation in college students even though the relationship between burdensomeness and ideation may be contingent on levels of cognitive risk factors. The present study thus examined the relationships between burdensomeness, hopelessness, coping competence, and suicidal ideation. Questionnaires were administered to 279 undergraduate students from a university in the Midwest United States. After controlling for depression, hopelessness, and coping competence, burdensomeness significantly predicted ideation and accounted for variance above and beyond the control variables. Moreover, the relationship between burdensomeness and suicidal ideation was significantly moderated by coping competence and hopelessness. The findings suggest that perceived burdensomeness plays a critical role in the risk for suicide in college students. More specifically, the findings suggest that coping competence and hopelessness can be ideal targets for interventions as changes in these variables may attenuate the association between perceived burdensomeness and suicidal ideation.
We evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell ...therapy are unknown in this population. RI was defined as creatinine clearance (CrCl) <50 mL/min. CrCl of <30 mL/min or dialysis dependence were defined as severe RI. The study cohort included 214 patients, 28 (13%) patients with RI, including 11 patients severe RI (dialysis, N=1). Patients with RI were older, more likely to be female and had higher likelihood of having Revised International Staging System stage 3 disease. Rates and severity of cytokine release syndrome (89% vs. 84%, grade ≥3: 7% vs. 2%) and immune effector cell-associated neurotoxicity syndrome (23% vs. 20%) were similar in patients with and without RI, respectively. Patients with RI had higher incidence of short-term grade ≥3 cytopenias, although cytopenias were similar by 3 months following CAR T-cell therapy. Renal function did not worsen after CAR T-cell therapy in patients with RI. Response rates (93% vs. 82%) and survival outcomes (median progression-free survival: 9 vs. 8 months; P=0.26) were comparable in patients with and without RI, respectively. Treatment with ide-cel is feasible in patients with RI, with a comparable safety and efficacy profile as patients without RI, with notable exception of higher short-term high-grade cytopenias.
The Neotropical butterfly Dryas iulia has been collected from several locations in Thailand and Malaysia since 2007, and has been observed breeding in the wild, using introduced Passiflora foetida as ...a larval host plant. The butterfly is bred by a butterfly house in Phuket, Thailand, for release at weddings and Buddhist ceremonies, and we hypothesized that this butterfly house was the source of wild, Thai individuals. We compared wing patterns and COI barcodes from two, wild Thai populations with individuals obtained from this butterfly house. All Thai individuals resemble the subspecies D. iulia modesta, and barcodes from wild and captive Thai specimens were identical. This unique, Thai barcode was not found in any of the 30 specimens sampled from the wild in the species' native range, but is most similar to specimens from Costa Rica, where many exporting butterfly farms are located. These data implicate the butterfly house as the source of Thailand's wild D. iulia populations, which are currently so widespread that eradication efforts are unlikely to be successful.
•Grade ≥ 3 cytopenias were at their worst at day 7 after ide-cel (94% of patients) but persisted in 40% at day 90, particularly thrombocytopenia.•Infections within 30 days of ide-cel were typically ...bacterial (68%) and severe (50%); moderate viral infections were more prevalent later.
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Idecabtagene vicleucel (ide-cel) was FDA-approved in March 2021 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On the KarMMa trial, grade ≥ 3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard-of-care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day-90 follow-up. Data were censored at day 100. Grade ≥ 3 cytopenia was present among 65% of patients at day 30 and 40% of patients at day 90. Granulocyte colony stimulating factor (G-CSF) was administered to 88%, packed red blood cell transfusions to 63%, platelet transfusions to 42%, thrombopoietin (TPO) agonists to 21%, intravenous immunoglobulin to 13%, and CD34+ stem cell boosts to 8%. At day 100, 19% and 13% of patients had ongoing use of TPO agonists and G-CSF, respectively. Infections occurred in 54% of patients and were grade ≥ 3 in 23%. Earlier infections in the first 30 days were typically bacterial (68%) and severe (50%). Later infections between days 31 and 100 were 50% bacterial and 42% viral; only 13% were grade ≥ 3. On univariate analysis, high pre-CAR-T marrow myeloma burden (≥ 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade ≥ 3 anemia at pre-LD were associated with grade ≥ 3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection.
Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients ...with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or soft tissue lesions non-contiguous from bone was classified as EMD. Time-to-event analyses were performed from date of ide-cel infusion. Among 351 patients, 84 (24%) had EMD prior to infusion. The median follow-up from ide-cel infusion was 18.2 months (95% CI: 17-19.3). The day 90 overall response rates (ORR) were 52% vs. 82% for the EMD and non-EMD cohorts, respectively (p < 0.001). The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1-6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2-12.6; p < 0.0001) for the non-EMD cohort. In a multivariable analysis, EMD was an independent predictor of inferior PFS hazard ratio 1.5 (1.1-2.2), p = 0.02. The median overall survival was 14.8 months 95% CI: 9-Not reached (NR) vs. 26.9 months (26.3 vs. NR, p = 0.006) for the EMD and non-EMD cohorts, respectively. Extramedullary disease represents an independent predictor of inferior day 90 ORR and PFS among patients treated with ide-cel. Keywords: BCMA CAR-T, Ide-cel, Relapsed/refractory myeloma, Radiation, Immunotherapy
Abstract Allogeneic hematopoietic cell transplantation is a potential curative treatment option for various malignant and nonmalignant hematologic disorders. Patients undergoing an allogeneic ...hematopoietic cell transplant are prescribed immune-suppressant therapies to facilitate hematopoietic donor-cell engraftment and prevent graft-versus-host disease. Drug–drug interactions may occur, owing to exposure to complex multidrug regimens with narrow therapeutic windows and high toxicity profiles. Here, we describe a unique case of a 65-year-old man with poor-risk acute myeloid leukemia who underwent a matched-sibling hematopoietic cell allograft. Sirolimus and tacrolimus were used for graft-versus-host disease prophylaxis. He developed oral thrush requiring treatment with clotrimazole troches, which subsequently resulted in serious renal toxicity attributed to supratherapeutic levels of sirolimus and tacrolimus. Patient renal function improved after temporarily holding both immune suppressants, and administering phenytoin to help induce sirolimus and tacrolimus metabolism. This case highlights sudden and serious toxicities that resulted from clotrimazole–sirolimus and clotrimazole–tacrolimus drug–drug interactions, even when administered topically.
El segundo volumen de la serie “Rescate arqueológico en la cuenca del Río Chixoy”, publicado en 1980 en el marco del proyecto RCP 500 del Centro Nacional de Investigación Científica de Francia, ...presenta la descripción del sitio más importantede esta zona : Cauinal (Capítulo 1), y de las excavaciones que fueron practicadas en el área, de noviembre de 1978 a mayo de 1979 (Capítulo 2). El Capítulo 3 es una amplia descripción de las estructuras encontradas en el grupo ceremonial A, que comprende los edificios más importantes de Cauinal ; mientras que el capítulo 4, describe el grupo residencial A. El capítulo 5, muestra las excavaciones del grupo B y de una parte del grupo C de Cauinal. Los grupos ceremoniales C-Sur y C-Norte son tratados en el Capítulo 6. Por último, los sitios secundarios del gran Cauinal son descritos en el Capítulo 7.
Idecabtagene vicleucel (ide-cel) is an autologous B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy approved for relapsed/refractory multiple myeloma (RRMM) on the basis of ...the phase II pivotal KarMMa trial, which demonstrated best overall and ≥ complete response rates of 73% and 33%, respectively. We report clinical outcomes with standard-of-care (SOC) ide-cel under the commercial Food and Drug Administration label.
Data were retrospectively collected from patients with RRMM who underwent leukapheresis as of February 28, 2022, at 11 US institutions with intent to receive SOC ide-cel. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines and managed according to each institution's policies. Responses were graded on the basis of the International Myeloma Working Group response criteria.
One hundred fifty-nine of 196 leukapheresed patients received ide-cel by data cutoff. One hundred twenty (75%) infused patients would have been ineligible for participation in the KarMMa clinical trial because of comorbidities at the time of leukapheresis. Any grade and grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 82/3% and 18/6%, respectively. Best overall and ≥ complete response rates were 84% and 42%, respectively. At a median follow-up of 6.1 months from chimeric antigen receptor T infusion, the median progression-free survival was 8.5 months (95% CI, 6.5 to not reached) and the median overall survival was 12.5 months (95% CI, 11.3 to not reached). Patients with previous exposure to B-cell maturation antigen-targeted therapy, high-risk cytogenetics, Eastern Cooperative Oncology Group performance status ≥ 2 at lymphodepletion, and younger age had inferior progression-free survival on multivariable analysis.
The safety and efficacy of ide-cel in patients with RRMM in the SOC setting were comparable with those in the phase II pivotal KarMMa trial despite most patients (75%) not meeting trial eligibility criteria.
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