Aortic Dissection and Renal Failure in a Patient with Severe Hypothyroidism

Acute aortic dissection (AAD) is a life-threatening condition associated with high morbidity and mortality. The most important recognized acquired cause that leads to dissection is chronic arterial hypertension. With respect to the anuria and renal failure, aortic dissection is not something that is always considered and is still not a very common presentation unless both renal arteries come off the false lumen of the dissection. However, when present, preoperative renal failure in patients with acute type B dissection has been noted to be an independent predictor of mortality. Early recognition and diagnosis is the key and as noted by previous studies as well, almost a third of these patients are initially worked up for other causes until later when they are diagnosed with aortic dissection. Here we present a case of a patient presenting with severe hypothyroidism, long-standing hypertension, and anuria. Through the case, we highlight the importance of having aortic dissection as an important differential in patients presenting with anuria who have a long standing history of uncontrolled hypertension. Pathophysiology relating to severe hypothyroidism-induced renal dysfunction is also discussed

Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma.

The innate immune response of airway epithelial cells to airborne allergens initiates the development of T cell responses that are central to allergic inflammation. Although proteinase allergens induce the expression of interleukin 25, we show here that epithelial matrix metalloproteinase 7 (MMP7) was expressed during asthma and was required for the maximum activity of interleukin 25 in promoting the differentiation of T helper type 2 cells. Allergen-challenged Mmp7(-/-) mice had less airway hyper-reactivity and production of allergic inflammatory cytokines and higher expression of retinal dehydrogenase 1. Inhibition of retinal dehydrogenase 1 restored the asthma phenotype of Mmp7(-/-) mice and inhibited the responses of lung regulatory T cells, whereas exogenous administration of retinoic acid attenuated the asthma phenotype. Thus, MMP7 coordinates allergic lung inflammation by activating interleukin 25 while simultaneously inhibiting retinoid-dependent development of regulatory T cells

TSG-6+ Cancer-Associated Fibroblasts Modulate Myeloid Cell Responses and Impair Anti-Tumor Response to Immune Checkpoint Therapy in Pancreatic Cancer

Resistance to immune checkpoint therapy (ICT) presents a growing clinical challenge. The tumor microenvironment (TME) and its components, namely tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), play a pivotal role in ICT resistance; however, the underlying mechanisms remain under investigation. In this study, we identify expression of TNF-Stimulated Factor 6 (TSG-6) in ICT-resistant pancreatic tumors, compared to ICT-sensitive melanoma tumors, both in mouse and human. TSG-6 is expressed by CAFs within the TME, where suppressive macrophages expressing Arg1, Mafb, and Mrc1, along with TSG-6 ligand Cd44, predominate. Furthermore, TSG-6 expressing CAFs co-localize with the CD44 expressing macrophages in the TME. TSG-6 inhibition in combination with ICT improves therapy response and survival in pancreatic tumor-bearing mice by reducing macrophages expressing immunosuppressive phenotypes and increasing CD8 T cells. Overall, our findings propose TSG-6 as a therapeutic target to enhance ICT response in non-responsive tumors

Treatment Outcomes in Patients With Metastatic Renal Cell Carcinoma With Sarcomatoid and/or Rhabdoid Dedifferentiation After Progression on Immune Checkpoint Therapy

BACKGROUND: Metastatic RCC with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is an aggressive disease associated with improved response to immune checkpoint therapy (ICT). The outcomes of patients treated with VEGFR-targeted therapies (TT) following ICT progression have not been investigated. PATIENTS AND METHODS: Retrospective review of 57 patients with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (S + R) dedifferentiation who received any TT after progression on ICT at an academic cancer center. Clinical endpoints of interest included time on TT, overall survival (OS) from initiation of TT, and objective response rate (ORR) by RECIST version 1.1. Multivariable models adjusted for epithelial histology, IMDC risk, prior VEGFR TT, and inclusion of cabozantinib in the post-ICT TT regimen. RESULTS: 29/57 patients had S dedifferentiation and 19 had R dedifferentiation. The most frequently used TT was cabozantinib (43.9%) followed by selective VEGFR TT (22.8%). The median time on TT was 6.4 months for all, 6.1 months for those with S dedifferentiation, 15.6 months for R dedifferentiation, and 6.1 months for S + R dedifferentiation. Median OS from initiation of TT was 24.9 months for the entire cohort, and the ORR was 20.0%. Patients with R dedifferentiation had significantly longer time on TT than those with S dedifferentiation (HR 0.44, 95% CI, 0.21-0.94). IMDC risk was associated with OS. CONCLUSIONS: A subset of patients with S/R dedifferentiation derive clinical benefit from TT after they have progressive disease on ICT. Patients with R dedifferentiation appeared to derive more benefit from TT than those with S dedifferentiation

Drought and salinity stresses induced physio-biochemical changes in sugarcane: an overview of tolerance mechanism and mitigating approaches

Sugarcane productivity is being hampered globally under changing environmental scenarios like drought and salinity. The highly complex nature of the plant responses against these stresses is determined by a variety of factors such as genotype, developmental phase of the plant, progression rate and stress, intensity, and duration. These factors influence plant responses and can determine whether mitigation approaches associated with acclimation are implemented. In this review, we attempt to summarize the effects of drought and salinity on sugarcane growth, specifically on the plant’s responses at various levels, viz., physiological, biochemical, and metabolic responses, to these stresses. Furthermore, mitigation strategies for dealing with these stresses have been discussed. Despite sugarcane’s complex genomes, conventional breeding approaches can be utilized in conjunction with molecular breeding and omics technologies to develop drought- and salinity-tolerant cultivars. The significant role of plant growth-promoting bacteria in sustaining sugarcane productivity under drought and salinity cannot be overlooked

Role of inactivating ARID1A mutation on the tumor microenvironment in response to immune checkpoint therapy

https://openworks.mdanderson.org/sumexp21/1132/thumbnail.jp