Research Spotlight

Posted July 15th 2016

Killer Cell Immunoglobulin-Like Receptor-Ligand Matching and Outcomes after Unrelated Cord Blood Transplantation in Acute Myeloid Leukemia.

Medhat Z. Askar M.D.

Medhat Z. Askar M.D.

Rocha, V., A. Ruggeri, S. Spellman, T. Wang, R. Sobecks, F. Locatelli, M. Askar, G. Michel, W. Arcese, A. P. Iori, D. Purtill, R. Danby, G. F. Sanz, E. Gluckman and M. Eapen (2016). “Killer cell immunoglobulin-like receptor-ligand matching and outcomes after unrelated cord blood transplantation in acute myeloid leukemia.” Biol Blood Marrow Transplant 22(7): 1284-1289.

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The effect of killer cell immunoglobulin-like receptor (KIR)-ligand matching on outcomes after unrelated cord blood (CB) transplantation was studied in 461 patients with acute myeloid leukemia, categorizing KIR ligand for HLA-C groups C1 and C2 and Bw4. Donor-recipient HLA matching considered allele-level matching at HLA-A, -B, -C, and -DRB1. Separate analyses were conducted for 6-7/8 HLA-matched and 3-5/8 HLA-matched transplants because HLA matching confounded KIR-ligand matching (ie, KIR-ligand mismatching was less likely with better HLA matching). All patients received single CB unit and myeloablative conditioning. There were no significant differences in nonrelapse mortality (NRM), relapse, and overall mortality by KIR-ligand match status. However, among recipients of 3-5/8 HLA-matched transplants, NRM (HR, 2.26; P = .008) and overall mortality (HR, 1.78; P = .008) but not relapse were higher with KIR-ligand mismatched (host-versus-graft direction) compared with KIR-ligand matched transplants. These data do not support selecting CB units based on KIR-ligand match status for transplants mismatched at 1 or 2 HLA loci. Although transplants mismatched at 3 or more HLA loci are not recommended, avoiding KIR-ligand mismatching in this setting lowers mortality risks.


Posted July 15th 2016

Ischiofemoral impingement and hamstring syndrome as causes of posterior hip pain: Where do we go next?

Hal David Martin D.O.

Hal David Martin D.O.

Martin, H. D., A. Khoury, R. Schroder and I. J. Palmer (2016). “Ischiofemoral impingement and hamstring syndrome as causes of posterior hip pain: Where do we go next?” Clin Sports Med 35(3): 469-486.

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Recent advances in understanding hip joint anatomy and biomechanics have contributed to improvement of diagnosis and treatment decisions for distal causes of deep gluteal syndrome (DGS). Ischiofemoral impingement and hamstrings syndrome are sources of posterior hip pain that can simulate symptoms of DGS. The combination of a comprehensive history and physical examination with imaging and ancillary testing are critical for diagnosis. Six key physical examination tests are described to differentiate distal versus proximal sources of extrapelvic posterior hip pain. Outcomes depend on patient compliance and the understanding of the entire anatomy, biomechanics, clinical presentation, and open versus endoscopic treatment options.


Posted July 15th 2016

Mechanical Ventilation in Patients with the Acute Respiratory Distress Syndrome and Treated with Extracorporeal Membrane Oxygenation: Impact on hospital and 30-day post-discharge survival.

Ariel Modrykamien M.D.

Ariel Modrykamien M.D.

Modrykamien, A. M., O. O. Hernandez, Y. Im, R. W. Walters, C. L. Schrader, L. E. Smith and B. Lima (2016). “Mechanical ventilation in patients with the acute respiratory distress syndrome and treated with extracorporeal membrane oxygenation: Impact on hospital and 30-day post-discharge survival.” Asaio j: 2016 June [Epub ahead of print].

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Mechanical ventilation support for ARDS patients involves the use of low tidal volumes and positive end-expiratory pressure. Nevertheless, the optimal ventilator strategy for ARDS patients undergoing ECMO therapy remains unknown.A retrospective analysis of a consecutive series of adult ARDS patients treated with V-V ECMO from 10/2012 to 05/2015 was performed. Mechanical ventilation, as well as demographic and clinical data were collected. We assessed the association between ventilator data and outcomes of interest. The primary outcome was hospital survival. Secondary outcome was 30-day survival post- hospital discharge.Sixty-four ARDS patients were treated with ECMO. Univariate analysis showed that plateau pressure was independently associated with hospital survival. Tidal volume, PEEP and plateau were independently associated with 30-day survival. Multivariate analysis, after controlling for covariates, revealed that a 1-unit increase in plateau pressure was associated with a 21% decrease in the odds of hospital survival (95% CI = 6.39% to 33.42%, p = .007). In regards to 30-day survival post-discharge, a 1-unit increase in plateau pressure was associated with a 14.4% decrease in the odds of achieving the aforementioned outcome (95% CI = 1.75% to 25.4%, p = .027). Also, a 1-unit increase in PEEP was associated with a 36.2% decrease in the odds of 30-day survival (95% CI = 10.8% to 54.4%, p = .009).Among ARDS patients undergoing ECMO therapy, only plateau pressure is associated with hospital survival. Plateau pressure and PEEP are both associated with 30-day survival post-hospital discharge.


Posted July 15th 2016

International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension.

Michael A.E. Ramsay M.D.

Michael A.E. Ramsay M.D.

Krowka, M. J., M. B. Fallon, S. M. Kawut, V. Fuhrmann, J. K. Heimbach, M. A. Ramsay, O. Sitbon and R. J. Sokol (2016). “International liver transplant society practice guidelines: Diagnosis and management of hepatopulmonary syndrome and portopulmonary hypertension.” Transplantation 100(7): 1440-1452.

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Two distinct pulmonary vascular disorders, hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) may occur as a consequence of hepatic parenchymal or vascular abnormalities. HPS and POPH have major clinical implications for liver transplantation. A European Respiratory Society Task Force on Pulmonary-Hepatic Disorders convened in 2002 to standardize the diagnosis and guide management of these disorders. These International Liver Transplant Society diagnostic and management guidelines are based on that task force consensus and should continue to evolve as clinical experience dictates. Based on a review of over 1000 published HPS and POPH articles identified via a MEDLINE search (1985-2015), clinical guidelines were based on, selected single care reports, small series, registries, databases, and expert opinion. The paucity of randomized, controlled trials in either of these disorders was noted. Guidelines are presented in 5 parts; I. Definitions/Diagnostic criteria; II. Hepatopulmonary syndrome; III. Portopulmonary hypertension; IV. Implications for liver transplantation; and V. Suggestions for future clinical research.


Posted July 15th 2016

Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination.

Hideki Ueno M.D.

Hideki Ueno M.D.

Kathania, M., P. Khare, M. Zeng, B. Cantarel, H. Zhang, H. Ueno and K. Venuprasad (2016). “Itch inhibits il-17-mediated colon inflammation and tumorigenesis by ror-gammat ubiquitination.” Nat Immunol: 2016 Jun [Epub ahead of print].

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Dysregulated expression of interleukin 17 (IL-17) in the colonic mucosa is associated with colonic inflammation and cancer. However, the cell-intrinsic molecular mechanisms by which IL-17 expression is regulated remain unclear. We found that deficiency in the ubiquitin ligase Itch led to spontaneous colitis and increased susceptibility to colon cancer. Itch deficiency in the TH17 subset of helper T cells, innate lymphoid cells and gammadelta T cells resulted in the production of elevated amounts of IL-17 in the colonic mucosa. Mechanistically, Itch bound to the transcription factor ROR-gammat and targeted ROR-gammat for ubiquitination. Inhibition or genetic inactivation of ROR-gammat attenuated IL-17 expression and reduced spontaneous colonic inflammation in Itch-/- mice. Thus, we have identified a previously unknown role for Itch in regulating IL-17-mediated colonic inflammation and carcinogenesis.