Response to radiation in renal medullary carcinoma

Renal medullary carcinoma (RMC) is a rare and highly aggressive malignancy arising from the renal medulla and found mostly in patients with sickle cell trait. RMC usually presents with widely metastatic disease. We describe a young man diagnosed with metastatic RMC who sustained a complete response to systemic chemotherapy but developed brain metastases with leptomeningeal involvement and subsequently had a partial response to brain irradiation. The use of radiation in the management of RMC is reviewed. Due to the apparent propensity for RMC to spread to the central nervous system, prophylactic treatment such as craniospinal irradiation should be considered along with chemotherapy in patients with metastatic RMC to potentially improve the progression-free interval

Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133605/1/bjh14046.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133605/2/bjh14046_am.pd

Allogeneic Transplantation Provides Durable Remission in a Subset of DLBCL Patients Relapsing after Autologous Transplantation

For diffuse large B-cell lymphoma (DLBCL) patients progressing after autologous haematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 503 patients who underwent alloHCT after disease progression/relapse following a prior autoHCT. The 3-year probabilities of non-relapse mortality, progression/relapse, progression-free survival (PFS) and overall survival (OS) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status (KPS) <80, chemoresistance, autoHCT to alloHCT interval <1-year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS<80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS, including KPS<80 (4 points), autoHCT to alloHCT interval <1-year (2 points) and chemoresistant disease at alloHCT (5 points). This CIBMTR prognostic model classified patients into four groups: low-risk (0 points), intermediate-risk (2-5 points), high-risk (6-9 points) or very high-risk (11 points), predicting 3-year PFS of 40, 32, 11 and 6%, respectively, with 3-year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long-term survival with alloHCT after a failed prior autoHCT

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Aiding and Abetting in International Criminal Law

To achieve justice for violations of international law such as genocide, torture, crimes against humanity, and war crimes, it is essential to address complicity for international crimes. Beginning in the 1990s, there was a proliferation of international and hybrid criminal tribunals, which sought to hold perpetrators of these crimes accountable and, in turn, generated an explosion of international criminal law jurisprudence. Nonetheless, the contours of aiding and abetting liability in international criminal law remain contested. Courts-both domestic and international-have long struggled to identify the proper legal standard for holding actors liable for aiding and abetting even the most serious violations of international law. That confusion has, in turn, produced inconsistent decisions. In the United States, for example, it has resulted in a circuit split, leading many to predict the issue will only be resolved by the U.S. Supreme Court. This Article aims to provide context and clarity in this area of international law. It explains and categorizes the existing jurisprudence on aiding and abetting, based on a comprehensive survey of every case decided by an international or hybrid criminal tribunal since Nuremberg. It argues that the search by U.S. courts for a single standard for aiding and abetting liability under international law when deciding cases arising under the Alien Tort Statute misunderstands the nature of the aiding and abetting jurisprudence-and, indeed, misunderstands the structure of international criminal law more generally. It explains that differentiated standards for aiding and abetting liability are often a result of purposive and functional pluralism. Put simply, different standards may be appropriate for different contexts. What appears to be a discontinuous and contradictory jurisprudence is, in fact, a set of calibrated standards that are often responsive to the particular context at hand. The Article concludes with recommendations for strengthening and enabling this functional pluralism in order to strengthen and enable international justice

Aiding and Abetting in International Criminal Law

To achieve justice for violations of international law such as genocide, torture, crimes against humanity, and war crimes, it is essential to address complicity for international crimes. Beginning in the 1990s, there was a proliferation of international and hybrid criminal tribunals, which sought to hold perpetrators of these crimes accountable and, in turn, generated an explosion of international criminal law jurisprudence. Nonetheless, the contours of aiding and abetting liability in international criminal law remain contested. Courts-both domestic and international-have long struggled to identify the proper legal standard for holding actors liable for aiding and abetting even the most serious violations of international law. That confusion has, in turn, produced inconsistent decisions. In the United States, for example, it has resulted in a circuit split, leading many to predict the issue will only be resolved by the U.S. Supreme Court. This Article aims to provide context and clarity in this area of international law. It explains and categorizes the existing jurisprudence on aiding and abetting, based on a comprehensive survey of every case decided by an international or hybrid criminal tribunal since Nuremberg. It argues that the search by U.S. courts for a single standard for aiding and abetting liability under international law when deciding cases arising under the Alien Tort Statute misunderstands the nature of the aiding and abetting jurisprudence-and, indeed, misunderstands the structure of international criminal law more generally. It explains that differentiated standards for aiding and abetting liability are often a result of purposive and functional pluralism. Put simply, different standards may be appropriate for different contexts. What appears to be a discontinuous and contradictory jurisprudence is, in fact, a set of calibrated standards that are often responsive to the particular context at hand. The Article concludes with recommendations for strengthening and enabling this functional pluralism in order to strengthen and enable international justice

Complete durable response of a pediatric anaplastic oligodendroglioma to temozolomide alone: Case report and review of literature

Anaplastic oligodendroglioma (AO) is rare in children. Treatment typically consists of varying combinations of surgery, chemotherapy, and radiotherapy. We present a pediatric case of frontal lobe AO with periventricular subcallosal extension and local leptomeningeal involvement. The isocitrate dehydrogenase (IDH) wild-type tumor was MGMT methylated and contained an ATRX mutation, BRAF alteration, and 1p/19q co-deletion; a combination of alterations mostly encountered in pediatric oligodendrogliomas. The patient underwent a near total resection and had a complete, durable response to temozolomide alone, suggesting that conservative management without radiation may be appropriate in some cases. We review the literature of this uncommon subtype of glioma in children