Disease-associated Mortality Research Articles

Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C.

Chronic infection with hepatitis C virus (HCV) affects an estimated 0.1%–2% of the pediatric population in the United States. While the clinical course in young children is indolent, adolescents who contract HCV have a disease course similar to adults, with a 26-fold increased risk of chronic liver disease-associated mortality, hepatocellular carcinoma, and need for curative liver transplantation. Furthermore, adolescent patients are entering childbearing age and carry a risk of passing HCV to their offspring via vertical transmission. Pegylated-interferon (PEG-IFN) with ribavirin was previously the only treatment option for pediatric patients with chronic hepatitis C (CHC), but the high likelihood of adverse reactions and subcutaneous route of administration limited its use and efficacy. Recently, the direct-acting antivirals (DAAs) ledipasvir (LDV) and sofosbuvir (SOF) were approved for adolescents with CHC. This review discusses the natural history of CHC in pediatric patients, data supporting LDV/SOF in adolescents, and ongoing studies evaluating DAAs in pediatric patients.

Spectrum of low-density lipoprotein receptor (LDLR) mutations in a cohort of Sri Lankan patients with familial hypercholesterolemia \u2013 a preliminary report

BackgroundHypercholesterolemia is a major determinant of cardiovascular disease-associated morbidity and mortality. Mutations in the LDL-receptor (LDLR) gene are implicated in the majority of the cases with familial hypercholesterolemia (FH). However, the spectrum of mutations in the LDLR gene in Sri Lankan patients has not been investigated. The objective of this study was to report the frequency and spectrum of variants in LDLR in a cohort of Sri Lankan patients with FH.MethodsA series of consecutive patients with FH, diagnosed according to Modified Simon Broome criteria or Dutch Lipid Clinic Network criteria at the University Medical Unit, Colombo, were recruited. Clinical data was recorded. DNA was extracted from peripheral blood samples. The LDLR gene was screened for genetic variants by Sanger sequencing.ResultsA total of 27 patients [13 (48%) males, 14 (52%) females; age range 24–73 years] were tested. Clinical features found among these 27 patients were: xanthelasma in 5 (18.5%), corneal arcus in 1 (3.7%), coronary artery disease (CAD) in 10 (37%), and a family history of hypercholesterolemia and/or CAD in 24 (88.9%) patients. In the entire cohort, mean total cholesterol was 356.8 mg/dl (±66.4) and mean LDL-cholesterol was 250.3 mg/dl (±67.7). Sanger sequencing of the 27 patients resulted in the identification of known pathogenic missense mutations in 5 (18.5%) patients. Four were heterozygotes for 1 mutation each. They were c.682G > C in 2 patients, c.1720C > A in 1 patient, and c.1855 T > A in 1 patient. One patient with severe FH phenotypes was a compound heterozygote for one known mutation, c.2289G > T, and another missense variant, c.1670C > G (p.Thr557Ser), with unknown functional impact. This latter variant has not been reported in any other population previously.ConclusionsThe frequency of known mutations in the LDLR gene in this cohort of patients was markedly low compared to frequencies reported in other populations. This highlights the likelihood of a complex, polygenic inheritance of FH in Sri Lankan patients, indicating the need for a comprehensive genetic evaluation that includes the screening for mutations in other genes that cause FH, such as APOB, PCSK9, and LDLRAP1.

Immunotherapy for Merkel cell carcinoma: a turning point in patient care

Merkel Cell carcinoma (MCC) is a rare but aggressive cancer, with an estimated disease-associated mortality as high as 46%. MCC has proven to be an immunologically responsive disease and the advent of immune checkpoint inhibitors has changed the treatment landscape for patients with advanced MCC. In this review, we discuss the rationale for the use of immune checkpoint inhibition, review current single agent therapies tested in and approved for MCC, and discuss emerging immunotherapeutic options for these patients.

Surgical outcomes in patients with resected insulinoma

Background: Insulinomas are rare functional pancreatic neuroendocrine tumors. In this large single-institution retrospective series we assess the surgical outcomes of resected insulinoma cases. Methods: The institutional pathology database was utilized for identification of all resected insulinoma cases within the last 10 years. Clinicopathological information and follow-up data were collected and assessed for postoperative patient outcomes. Results: In the studied period, 40 patients with resected insulinoma were identified; they were predominantly white (80%) and female (65%), with a median age of 50 years (IQR 38-58). All patients presented with Whipple’s triad (symptomatic hypoglycemia, blood glucose level <50 mg/dL, and symptom relief with glucose administration), accompanied occasionally by weight gain (n = 18, 45%), personality changes (n = 33, 82.5%), or syncopal episodes (n = 18, 45%). In four cases (10%) the lesion was associated with MEN-1 syndrome and the rest were sporadic. Endoscopic ultrasound was the main diagnostic tool for tumor localization; lesion enucleation was performed for smaller lesions in 25% of the patients. The median tumor size was 13 mm (IQR 10-21), and most lesions were unifocal (n = 34, 85%) and located in the distal pancreas (n = 23, 57.5%). One patient (2.5%) had a distant liver metastasis at diagnosis that was also resected; he underwent a second liver resection for recurrence 3 years later and the patient is alive 9 years after initial presentation. Insulinoma recurrence was also identified locally in a patient with a previous R1 resection 2 years later (2.5%). Median patient follow-up was 16 months (IQR 4-57) and disease-associated mortality was zero. Conclusion: Insulinomas are rare pancreatic neuroendocrine tumors with favorable biology. Surgical resection is the treatment of choice with excellent prognosis.

Skin signs of primary immunodeficiencies: how to find the genes to check.

Primary immunodeficiencies (PIDs) are a heterogeneous group of rare diseases that result from defects in immune system development and/or function. The clinical manifestations of PIDs are highly variable, but most disorders involve at least an increased susceptibility to infection. Furthermore, cutaneous manifestations are very common in PIDs. As an easily accessible organ, the skin can be crucial for early diagnosis and treatment. This is relevant for preventing significant disease-associated morbidity and mortality. We provide a table that enables the reader to find the possible diseases and corresponding gene defects based on the skin manifestations of the suspected PIDs. To our knowledge, this is the first review that allows the reader to find relevant PIDs and the respective gene defects through solitary or combined skin signs.

Perioperative Treatment in Gastric Cancer—Developments in Patient Selection

Gastric cancer (GC) is a major public health issue. It is considered the 5th most common cancer diagnosed worldwide and it is one of the main causes of malignant disease-associated morbidity and mortality. The cornerstone of curative treatment is still surgery, and since the rate of relapse is high, a multidisciplinary approach is warranted in most developed countries. And while there have been recent developments in the perioperative scenario namely the FLOT regimen, little has advanced considering patient selection. We have reviewed the major trials in this setting and provide some insights from recently reported microsatellite instability (MSI) in a subgroup analysis in the MAGIC trial patients that seem to suggest an opportunity to patient selection. Furthermore, GC subtyping may prove helpful selecting candidates to immunotherapy or even multimodal therapy in the future. As the paradigm is moving towards a precision oncology model, GC patient selection remains one the biggest challenges in oncology but seems closer to clinical practice reality as new developments are being reported.

Impact of disease on the survival of three commercially fished species.

Recent increases in emergent infectious diseases have raised concerns about the sustainability of some marine species. The complexity and expense of studying diseases in marine systems often dictate that conservation and management decisions are made without quantitative data on population-level impacts of disease. Mark-recapture is a powerful, underutilized, tool for calculating impacts of disease on population size and structure, even in the absence of etiological information. We applied logistic regression models to mark-recapture data to obtain estimates of disease-associated mortality rates in three commercially important marine species: snow crab (Chionoecetes opilio) in Newfoundland, Canada, that experience sporadic epizootics of bitter crab disease; striped bass (Morone saxatilis) in the Chesapeake Bay, USA, that experience chronic dermal and visceral mycobacteriosis; and American lobster (Homarus americanus) in the Southern New England stock, that experience chronic epizootic shell disease. All three diseases decreased survival of diseased hosts. Survival of diseased adult male crabs was 1% (0.003-0.022, 95% CI) that of uninfected crabs indicating nearly complete mortality of infected crabs in this life stage. Survival of moderately and severely diseased striped bass (which comprised 15% and 11% of the population, respectively) was 84% (70-100%, 95% CI), and 54% (42-68%, 95% CI) that of healthy striped bass. The disease-adjusted yearly natural mortality rate for striped bass was 0.29, nearly double the previously accepted value, which did not include disease. Survival of moderately and severely diseased lobsters was 30% (15-60%, 95% CI) that of healthy lobsters and survival of mildly diseased lobsters was 45% (27-75%, 95% CI) that of healthy lobsters. High disease mortality in ovigerous females may explain the poor recruitment and rapid declines observed in this population. Stock assessments should account for disease-related mortality when resource management options are evaluated.

Rodeo™ Herbicide Negatively Affects Blanchard's Cricket Frogs (Acris blanchardi) Survival and Alters the Skin-Associated Bacterial Community

Abstract Disease-associated mortality is a leading cause of amphibian declines and extinctions worldwide. Understanding the influence of land-management practices, like herbicide use, on amphibian immune defense traits could guide changes to improve conservation outcomes. Amphibians are partially protected from pathogens by two skin-associated immune defense traits: bacterial communities inhabiting their skin, and antimicrobial peptides secreted by the skin. Utilizing the Blanchard's Cricket Frog (Acris blanchardi), a declining North American amphibian species, as our model, we manipulated Rodeo™ aquatic herbicide concentration and the life stage at which Rodeo exposure occurred. We assessed juvenile survival, time to metamorphosis, juvenile mass, and skin-associated immune defense traits. We found a 37% decrease in survival of larvae exposed to 2.5 mg a.e. L−1 (acid equivalent) compared to controls despite that this commercial herbicide formulation does not contain an added surfactant. Surviving larvae e...

Rheumatoid arthritis: The benefits of early treatment after decades.

Early, targeted treatment improves the outcome of rheumatoid arthritis, reducing disease-associated disability and mortality. Until now, it was unknown whether these beneficial effects extended beyond 10 years following initial therapy. Could these effects persist even after 20 years?

R-spondin 2 promotes proliferation and migration via the Wnt/β-catenin pathway in human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of malignant disease-associated mortality, particularly in China. The RSPO2 (R-spondin 2) gene is evolutionarily conserved in vertebrates and is involved in developmental and physiological processes. Importantly, RSPO2 has been reported to be associated with colon cancer and potentiate the Wnt/β-catenin signaling pathway. In the present study, enhanced expression of RSPO2 in HCC was observed using tissue microarray. Similarly, the expression level of RSPO2 was higher in HepG2, Huh7 and Hep3B cells but lower in Bel7404 and QGY7703 cells compared with human normal QSG7701 liver cells. Subsequently, gain-of-function studies indicated that RSPO2 promotes the proliferation and migration of QGY7703 cells based on lentivirus-based gene delivery. Furthermore, it was revealed that p21 and leptin, rather than vascular endothelial growth factor-A, are involved in the function of RSPO2 in QGY7703 cells. Particularly, the signal transducer and activator of transcription 3 (STAT3) and Wnt/β-catenin signaling pathways are involved in this process. Overexpression of RSPO2 resulted in the elevated expression of phosphorylated STAT3, β-catenin and c-Myc. Therefore, the present study is beneficial to the understanding of RSPO2-involved liver cancer transformation and drug discovery.

Iron accelerates hemoglobin oxidation increasing mortality in vascular diseased guinea pigs following transfusion of stored blood.

Non-transferrin-bound iron (NTBI) and free hemoglobin (Hb) accumulate in circulation following stored RBC transfusions. This study investigated transfusion, vascular disease, and mortality in guinea pigs after stored RBC transfusion alone and following cotransfusion with apo-transferrin (apo-Tf) and haptoglobin (Hp). The effects of RBC exchange transfusion dose (1, 3, and 9 units), storage period (14 days), and mortality were evaluated in guinea pigs with a vascular disease phenotype. Seven-day mortality and the interaction between iron and Hb as cocontributors to adverse outcome were studied. Concentrations of iron and free Hb were greatest after transfusion with 9 units of stored RBCs compared with fresh RBCs or stored RBCs at 1- and 3-unit volumes. Nine units of stored RBCs led to mortality in vascular diseased animals, but not normal animals. One and 3 units of stored RBCs did not cause a mortality effect, suggesting the concomitant relevance of NTBI and Hb on outcome. Cotransfusion with apo-Tf or Hp restored survival to 100% following 9-unit RBC transfusions in vascular diseased animals. Our data suggest that increases in plasma NTBI and Hb contribute to vascular disease-associated mortality through iron-enhanced Hb oxidation and enhanced tissue injury.

Biomarkers for the diagnosis of Alzheimer's disease in clinical practice: an Italian intersocietal roadmap

Biomarkers of brain amyloidosis and neurodegeneration/synaptic dysfunction are featured in recent diagnostic criteria for Alzheimer's disease. Several gaps in our knowledge, however, need to be filled before they can be adopted clinically. The aim of this article is to describe a roadmap, developed by a multidisciplinary task force, to rationally implement biomarkers for Italian Memory Clinics. This roadmap is based on a framework comprising 5 sequential phases: identification of leads for potentially useful biomarkers; development of clinical assays for clinical disease; evaluation of detection of early stages; definition of operating characteristics in relevant populations; and estimation of reducing disease-associated mortality, morbidity, and disability. The roadmap was devised by identifying current evidence of validity, still missing evidence, and action needed to collect this missing evidence. With appropriate adaptation to local, country-specific circumstances, the roadmap can be translated to other countries.

Prognostic value of metabolic parameters determined by preoperative ¹⁸F-FDG PET/CT in patients with uterine carcinosarcoma.

ObjectiveTo evaluate the prognostic value of metabolic parameters measured by preoperative 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in patients with uterine carcinosarcoma (UCS).MethodsData of 55 eligible patients with UCS who underwent preoperative 18F-FDG PET/CT and surgical staging were analyzed retrospectively. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV2.5), and total lesion glycolysis (TLG2.5) of the primary tumors were measured using a SUV threshold of 2.5. The optimal cutoff value of each parameter was determined by time-dependent receiver operating characteristic curve, and its impact on progression-free survival and overall survival was evaluated by Cox proportional hazards model.ResultsDuring a median follow-up period of 29 (range, 1.5–109.4) months, 47.3% (26/55) of the patients experienced disease progression, and the disease-associated mortality rate was 43.6% (24/55). Univariate analysis determined that hazard ratios (HRs) for disease progression for SUVmax (≥8.33), MTV2.5 (≥63.92 mL), and TLG2.5 (≥396.16) were 1.930 (95% confidence interval [CI]=0.793–4.701), 3.264 (95% CI=1.466–7.268), and 2.692 (95% CI=1.224–5.924), respectively. And, HRs for death were 1.979 (95% CI=0.774–5.060), 2.764 (95% CI=1.217–6.274), and 2.721 (95% CI=1.198–6.182), respectively. While peritoneal cytology, histology, and tumor diameter were independent prognostic factors in multivariate analysis, MTV and TLG were not.ConclusionThough MTV and TLG of primary UCS were not independent predictors compared to surgically obtained data, MTV and TLG of primary UCS may provide useful information on prognosis especially in patients who are not able to undergo surgical staging.

Parotid abscess: A clinical analysis of 40 cases in a tertiary care hospital in India

Parotid abscess is a rare disease which has been associated with high mortality in the past. We present our experience in managing the disease in one of the largest series in published literature. ObjectivesTo study the clinical, microbiological profile and management of parotid abscess in a tertiary care hospital. MethodologyA retrospective review of all patients diagnosed to have parotid abscess between January 2006 and January 2016 was undertaken. ResultsForty patients were diagnosed to have parotid abscess with a male:female ratio of 2:1. Brawny induration without fluctuation was the most common presentation. Nine patients developed parotid abscess while being treated in the intensive care unit for various medical illnesses. The majority of the patients had immunosuppression in the form of uncontrolled diabetes mellitus or systemic auto-immune disease. Thirty-three patients required incision and drainage, the remaining were treated with antibiotics alone or with the aspiration of the pus. Staphylococcus, Streptococcus, and Klebsiella were the most common micro-organisms grown. The organisms were consistently sensitive to the first line antibiotics (Cloxacillin, Amoxicillin–clavulanic acid, and Gentamicin). Disease-associated mortality was present in one patient. ConclusionParotid abscess is a disease that presents in immuno-compromised patients. First line antibiotics and surgical decompression of the tense parotid fascia and drainage of the abscess is the treatment of choice. Disease-specific mortality is low when appropriate treatment is instituted.

Chronic wasting disease in white-tailed deer: infection, mortality, and implications for heterogeneous transmission.

Chronic wasting disease (CWD) is a fatal neurodegenerative disease affecting free-ranging and captive cervids that now occurs in 24 U.S. states and two Canadian provinces. Despite the potential threat of CWD to deer populations, little is known about the rates of infection and mortality caused by this disease. We used epidemiological models to estimate the force of infection and disease-associated mortality for white-tailed deer in the Wisconsin and Illinois CWD outbreaks. Models were based on age-prevalence data corrected for bias in aging deer using the tooth wear and replacement method. Both male and female deer in the Illinois outbreak had higher corrected age-specific prevalence with slightly higher female infection than deer in the Wisconsin outbreak. Corrected ages produced more complex models with different infection and mortality parameters than those based on apparent prevalence. We found that adult male deer have a more than threefold higher risk of CWD infection than female deer. Males also had higher disease mortality than female deer. As a result, CWD prevalence was twofold higher in adult males than females. We also evaluated the potential impacts of alternative contact structures on transmission dynamics in Wisconsin deer. Results suggested that transmission of CWD among male deer during the nonbreeding season may be a potential mechanism for producing higher rates of infection and prevalence characteristically found in males. However, alternatives based on high environmental transmission and transmission from females to males during the breeding season may also play a role.

Therapeutic potential of adipose stem cell-derived conditioned medium against pulmonary hypertension and lung fibrosis.

Pulmonary hypertension (PH) and pulmonary fibrosis (PF) are life threatening cardiopulmonary diseases. Existing pharmacological interventions have failed to improve clinical outcomes or reduce disease-associated mortality. Emerging evidence suggests that stem cells offer an effective treatment approach against various pathological conditions. It has been proposed that their beneficial actions may be mediated via secretion of paracrine factors. Herein, we evaluated the therapeutic potential of conditioned media (CM) from adipose stem cells (ASCs) against experimental models of PH and PF. Monocrotaline (MCT) or bleomycin (Bleo) was injected into male Sprague-Dawley rats to induce PH or PF respectively. A subset of MCT and Bleo animals were treated with ASCs or CM. Echocardiographic and haemodynamic measurements were performed at the end of the study. Lung and heart tissues were harvested for RNA, protein and histological measurements. CM treatment attenuated MCT-induced PH by improving pulmonary blood flow and inhibiting cardiac remodelling. Further, histological studies revealed that right ventricular fibrosis, pulmonary vessel wall thickness and pericyte distribution were significantly decreased by CM administration. Likewise, CM therapy arrested the progression of PF in the Bleo model by reducing collagen deposition. Elevated expression of markers associated with tissue remodelling and inflammation were significantly reduced in both PF and PH lungs. Similar results were obtained with ASCs administration. Our study indicates that CM treatment is as effective as ASCs in treating PH and PF. These beneficial effects of CM may provide an innovative approach to treat cardiopulmonary disorders.

Mortality reduction among persons with type 2 diabetes: (−)-Epicatechin as add-on therapy to metformin?

Diabetes has become a worldwide epidemic, and is growing at a rapid rate with drastic projections for developing countries. Mexico occupies the ninth place worldwide for type 2 diabetes prevalence, and in the foreseeable future, it is expected rise to the seventh place. Myocardial infarction is the most common cause of death in these patients. Although several drugs are approved for the treatment of type 2 diabetes that reduce factors associated with myocardial infarction, an excess risk of death is still present. In this regard, the American Diabetes Association recommends metformin (oral glucose lowering drug) as the first-line therapy in type 2 diabetic subjects, based on its amply confirmed positive metabolic effects; however, its capacity to reduce cardiovascular mortality in type 2 diabetic subjects is inconclusive. Thus, mortality reduction in these patients has been an elusive goal, and is therefore, imperative to evaluate new pharmacological interventions that may favorably impact mortality in these individuals. On the other hand, epidemiological studies have suggested that moderate consumption of cacao-derived products (i.e., chocolate and cocoa) may reduce the risk of diabetes, myocardial infarction, and cardiovascular disease-associated mortality. Moreover, interventional studies have also suggested that dark chocolate and cocoa consumption is vasculoprotective in normal and type 2 diabetic individuals. (−)-Epicatechin ((−)-EPI) is the main flavanol present in cacao, and suggested to be responsible for the beneficial effects observed after dark chocolate/cocoa consumption. Interestingly, in vivo studies have evidenced the capacity of (−)-EPI to reduce infarct size, and preserve cardiac mechanics in rodent models of ischaemia–reperfusion injury. Nonetheless, long-term studies using (−)-EPI and evaluating its effects on mortality are lacking. Thus, based on their particular properties, it is valid to speculate that (−)-EPI and metformin in conjunction may favorably impact mortality in type 2 diabetic individuals. Here, we provide the evidence that allow us to propose our hypothesis, and further suggest a reasonable way to perform the study needed for such investigation.

Repulsive guidance molecule B inhibits metastasis and is associated with decreased mortality in non-small cell lung cancer.

Repulsive guidance molecules (RGMs) are co-receptors of bone morphogenetic proteins (BMPs) and programmed death ligand 2 (PD-L2), and might be involved in lung and other cancers. We evaluated repulsive guidance molecule B (RGMB) expression in 165 non-small cell lung cancer (NSCLC) tumors and 22 normal lung tissue samples, and validated the results in an independent series of 131 samples. RGMB was downregulated in NSCLC (P ≤ 0.001), possibly through promoter hypermethylation. Reduced RGMB expression was observed in advanced-stage tumors (P = 0.017) and in tumors with vascular invasion (P < 0.01), and was significantly associated with poor overall survival (39 vs. 62 months, P < 0.001) and with disease-associated patient mortality (P = 0.015). RGMB knockdown promoted cell adhesion, invasion and migration, in both NSCLC cell lines and an in vivo mouse model, which enhanced metastatic potential. Conversely, RGMB overexpression and secretion suppressed cancer progression. The tumor-suppressing effect of RGMB was exerted through inhibition of the Smad1/5/8 pathway. Our results demonstrate that RGMB is an important inhibitor of NSCLC metastasis and that low RGMB expression is a novel predictor or a poor prognosis.

New molecular insights in diabetic nephropathy.

Diabetes mellitus represents one of the major causes of functional kidney impairment. The review highlights the most significant steps made over the last decades in understanding the molecular basis of diabetic nephropathy (DN), which may provide reliable biomarkers for early diagnosis and prognosis, along with new molecular targets for personalized medicine. There is an increased interest in developing new therapeutic strategies to slow DN progression for improving patients' quality of life and reducing all-cause morbidity and disease-associated mortality. It is highly important to have a science-based medical attitude when facing diabetic patients with associated comorbidities and risk of rapid evolution toward end-stage renal disease. The data discussed herein were mainly from MEDLINE and PubMed articles published in English from 1990 to 2015 and from up-to-date. The search term was "diabetic nephropathy and oxidative stress".

Impact of Unbalanced Translocation Der(1;7)(q10;p10) and -7/Del(7q) on the Prognostic Value after Allogeneic Hematopoietic Stem Cell Transplantation in Myelodysplastic Syndromes: A Nationwide Retrospective Study

Background:Poor-risk karyotypic abnormalities in patients with myelodysplastic syndromes (MDS) are known to have a negative impact on outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Abnormalities in chromosome 7 have classically been categorized as a poor-risk karyotype, but comprise various patterns, in which the unbalanced translocation der(1;7)(q10;p10) and -7/del(7q) are frequently observed. To accurately estimate outcomes after allo-HSCT in MDS patients with der(1;7)(q10;p10) and -7/del(7q), we herein conducted a retrospective study among adults with de novo MDS.Methods:The clinical data of patients who had either der(1;7)(q10;p10) or -7/del(7q) as the sole karyotypic abnormality and underwent allo-HSCT between January 1999 and December 2012 were collected from the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation. Patients with a normal karyotype (NK) were included as a reference group. We used the French-American-British classification to define the disease status at HSCT, as described previously (Saber W, et al. Blood 2013.); refractory anemia with excess blasts (RAEB) or RAEB in transformation at any time between diagnosis and HSCT was considered to be an advanced disease status, while others were regarded as an early disease status. Causes of death were categorized into disease-associated mortality (DAM) or transplant-related mortality (TRM); the former was defined as death after the relapse or progression of MDS, while the latter was defined as any death other than that due to MDS. Cox proportional hazards regression models were used to evaluate variables potentially affecting overall survival (OS). Fine and Gray proportional hazards models were used to evaluate variables potentially affecting DAM and TRM. DAM and TRM were estimated using cumulative incidence curves to accommodate competing events.Results:Twenty-three MDS patients with der(1;7)(q10;p10), 29 with -7/del(7q), and 347 with NK were identified among those who underwent HSCT with an early disease status. The estimated 5-year OS, DAM, and TRM by cytogenetic subcategories were as follows; 47.3%, 9.9% and 42.8% for patients with der(1;7)(q10;p10); 63.5%, 11.1%, and 25.4% for patients with -7/del(7q); and 69.5%, 5.8%, and 24.7% for patients with NK, respectively. The univariate and multivariate analyses on OS, DAM, and TRM did not identify any significant differences among the cytogenetic subcategories tested.Sixty-nine patients with der(1;7)(q10;p10), 75 with -7/del(7q), and 511 with NK were identified among those who underwent HSCT with an advanced disease status. The estimated 5-year OS, DAM, and TRM by cytogenetic subcategories were as follows; 47.2%, 18.6% and 34.2% for patients with der(1;7)(q10;p10); 33.4%, 36.8%, and 29.8% for patients with -7/del(7q); and 48.0%, 21.8%, and 30.2% for patients with NK, respectively. The univariate analysis revealed that the presence of -7/del(7q) was associated with lower OS (P =.012) and higher DAM (P =.001), whereas that of der(1;7)(q10;p10) showed similar OS (P =.781) and DAM (P =.858) to those with NK. In the multivariate analysis, the presence of -7/del(7q) was significantly associated with lower OS (Hazard ratio (HR) [95% confidential interval], 1.40 [1.01-1.92]; P =.041) and higher DAM (HR, 2.02 [1.24-3.28]; P =.005) than those with NK. No significant differences were observed in TRM among the 3 cytogenetic subcategories.Conclusion:Patients with der(1;7)(q10;p10) may benefit from allo-HSCT, achieving similar outcomes to those of patients with NK. However, the presence of -7/del(7q) adversely affected OS and DAM with significance in patients with an advanced disease status. DisclosuresMiyazaki:Shin-bio: Honoraria; Chugai: Honoraria, Research Funding; Sumitomo Dainippon: Honoraria; Celgene Japan: Honoraria; Kyowa-Kirin: Honoraria, Research Funding.