What's known on the subject? and What does the study add?Hydrogen sulphide (H2S) has recently been classified as a member of the gasotransmitter family. Its physiological and pathophysiological effects are rapidly expanding with numerous studies highlighting the protective effects of H2S on ischaemia‐reperfusion injury (IRI) in various organ systems, e.g. heart, liver, CNS and lungs. The mechanisms behind its protective effects reside in its vasodilatory, anti‐inflammatory and anti‐oxidant characteristics. These specific mechanistic profiles appear to be different across different tissues and models of IRI.We recently showed that supplementation of preservation solutions with H2S during periods of prolonged cold renal storage and subsequent renal transplantation leads to a massive and significant survival, functional and tissue protective advantage compared with storage in standard preservation solution alone. However, there have only been a few studies that have evaluated the effects of H2S against warm renal IRI; although these studies have focused primarily upon shorter periods of warm renal pedicle clamping, they have shown a clear survival benefit to H2S supplementation. The present study adds to the existing literature by evaluating the effects of H2S in a model of warm IRI with clinically relevant, prolonged warm ischaemia‐reperfusion times (1 h ischaemia, 2 h reperfusion). We show an unprecedented view into real‐time renal and hepatic perfusion with intravital microscopy throughout the reperfusion period. We show, for the first time, that supplemental H2S has multiple protective functions against the warm IRI‐induced tissue damage, which may be clinically applicable to both donation after cardiac death models of renal transplantation, as well as to uro‐oncological practices requiring surgical clamping of the renal pedicle, e.g. during a partial nephrectomy.OBJECTIVE To determine the protective role of supplemental hydrogen sulphide (H2S) in prolonged warm renal ischaemia‐reperfusion injury (IRI) using real‐time intravital microscopy (IVM). MATERIALS AND METHODS Uninephrectomised Lewis rats underwent 1 h of warm ischaemia and 2 h of reperfusion during intraperitoneal treatment with phosphate buffer saline (IRI, n= 10) or 150 µmol/L NaHS (IRI+H2S, n= 12) and were compared with sham‐operated rats (n= 9). Blood was collected for measurement of serum creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). IVM was performed to assess renal and hepatic microcirculation. Kidneys were sectioned for histology and real‐time quantitative polymerase chain reaction for markers of inflammation. RESULTS The mean (sd) Cr concentration raised to 72.8 (2.5) µmol/L after IRI from 11.0 (0.7) µmol/L (sham) but was partially inhibited with H2S to 62.8 (0.9) µmol/L (P < 0.05). H2S supplementation during IRI increased renal capillary perfusion on IVM, and improved acute tubular necrosis and apoptotic scores on histology (P < 0.05). Supplemental H2S decreased expression of the pro‐inflammatory markers toll‐like receptor 4, tumour necrosis factor α, interleukin 8, C‐C chemokine receptor type 5, interferon γ and interleukin 2 (P < 0.05). Distant organ (liver) dysfunction after renal IRI was limited with H2S supplementation: blunting of the ALT and AST surge, decreased hepatic sinusoidal vasodilation, and decreased leukocyte infiltration in post‐sinusoidal venules (P < 0.05). H2S supplementation directly inhibited interleukin 8‐induced neutrophil chemotaxis in vitro (P < 0.05). CONCLUSIONS These findings are the first to show the real‐time protective role of supplemental H2S in prolonged periods of warm renal IRI, perhaps acting by decreasing leukocyte migration and limiting inflammatory responses. The protective effects of H2S suggest potential clinical applications in both donors after cardiac death models of renal transplantation and oncological practices requiring vascular clamping.

Complex support needs are involved in coping with a diagnosis of melanoma. The purpose of this study was to determine the perceived social support levels and utilization of adaptive and maladaptive coping strategies by Canadian melanoma patients. The impact of social support level on coping strategy utilization was also examined. Social support and coping strategies were assessed using the Medical Outcomes Study Social Support Survey (MOS-SSS) and the 28-item Brief COPE, respectively. Perceived levels of emotional/informational support were significantly lower than affectionate support and positive social interaction. Acceptance, active coping, and use of emotional support were the most frequently utilized coping strategies. Patients with higher perceived levels of social support had significantly higher adaptive coping scores than patients with lower levels of social support. Health care professionals have an important role in promoting awareness of and access to emotional and informational support resources in order to improve perceived social support levels.

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Background. Dyskeratosis congenita (DC) is a telomere biology disorder with a high risk of bone marrow failure, cancer, pulmonary and liver disease. Mutation in multiple telomere related genes including DKC1, TINF2, RTEL1, TERC, TERT, WRAP53, CTC1, NOP10, NHP2 and TPP1 have been reported. Patients with mutations in several DC genes (e.g. heterozygous TINF2, hemizygous DKC1 and biallelic RTEL1 mutations) typically tend to have a particularly serious disease with severe bone marrow failure (SBMF) at a young age, non-hematological manifestations and very short telomeres. Currently, allogeneic hematopoietic stem cell transplantation (HSCT) is the only available curative treatment for bone marrow failure and leukemia in DC patients. Relatively few case series of patients with DC undergoing HSCT have been reported, which generally suggested a poor outcome. The present study aimed to characterize the outcome of HSCT in a Canadian cohort of patients with DC and determine potential relationships between outcome and genotype. Methods. The Canadian Inherited Marrow Failure Registry (CIMFR) is a multicenter registry that includes tertiary centers that care for IBMFS patients across all Canadian provinces. Patients with DC who had been enrolled in CIMFR and underwent HSCT between January 2001 and December 2019 were included. Data were extracted from the CIMFR database. Results. Among 35 patients with DC enrolled in the CIMFR, 11 underwent HSCT. Seven patients were male. Median age at presentation, diagnosis and HSCT was 2.1 years (range: 0 to 9.13s), 5.5 years (range: 1.94 to 35.25), and 7.0 years (range; 0.5-37), respectively. The diagnosis of 3 patients was made after HSCT. Median follow up time from HSCT was 5.89 years (range; 0.2-14.0 years). Among transplanted patients, five had TINF2 mutations, two had RTEL1 mutations, and one patient had DKC1 mutation. Eight patients underwent HSCT for severe bone marrow failure, and three patients for single or multilneage cytopenia. All patients had normal bone marrow karyotype before HSCT. All patients had a full matched donor; two were related and nine were unrelated. Ten patients received reduced-intensity conditioning, and one received myeloablative conditioning. Two patients experienced engraftment failure and underwent a second HSCT. Five years and ten years overall survival after HSCT were 90.9% (95% CI 73.9-100%) and 80% (95% CI 27.2- 97.5%), respectively; however, complications and deaths started appearing thereafter, mainly in patients with TINF2 mutation. All five patients with TINF2 mutation died, and other patients were alive. The causes of death were: 1) pulmonary fibrosis (N=2), 2) gastrointestinal bleeding (N=2), and 3) EBV infection (N=1). Two patients were diagnosed with pulmonary fibrosis after 8 and 11 years from HSCT and died 13.7 and 14 years post-transplant. Two patients had gastrointestinal bleeding after 3.9 years and 4.8 years from HSCT and died 6.6 and 5.7 years post-transplant. Of the patients with GI bleeding, both had hepatic fibrosis and one had pulmonary fibrosis. Summary: In this series, most patients with DC had resolution of the bone marrow failure and relatively good quality of life in the first few years post HSCT. However, longer outcome in the patients with TINF2 mutation was dismal because of DC-related complications, especially pulmonary fibrosis and gastrointestinal bleeding. Effective therapies to prevent these complications are critically needed. Additional reports about HSCT outcome of patients with DC are necessary to characterize HSCT in patients with other genetic groups and to replicate the above results in TINF2 patients. Disclosures No relevant conflicts of interest to declare.