Cause Of Late Death Research Articles

Lupus-like manifestations after allogenic hematopoietic stem cell transplantation: a rarecase of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GvHD) is the leading cause of late death in allogenic hematopoietic stem cell transplantation recipients, of which the kidney is a potential target. In this article, we report an extremely rare case of chronic GvHD, characterized by immune complex-mediated diffuse proliferative glomerulonephritis and various autoantibodies detected in the serum; it is the first case of lupus-like chronic GvHD reported to date. The patient responded well to intensive immunosuppressive therapy and reached complete remission. Mycophenolate mofetil was more effective than tacrolimus in this case, suggesting that treatment of kidney diseases associated with chronic GvHD should be based on pathogenesis and pathological patterns.

An orally administered bacterial membrane protein nanodrug ameliorates doxorubicin cardiotoxicity through alleviating impaired intestinal barrier

The cardiotoxicity caused by Dox chemotherapy represents a significant limitation to its clinical application and is a major cause of late death in patients undergoing chemotherapy. Currently, there are no effective treatments available. Our analysis of 295 clinical samples from 132 chemotherapy patients and 163 individuals undergoing physical examination revealed a strong positive correlation between intestinal barrier injury and the development of cardiotoxicity in chemotherapy patients. We developed a novel orally available and intestinal targeting protein nanodrug by assembling membrane protein Amuc_1100 (obtained from intestinal bacteria Akkermansia muciniphila), fluorinated polyetherimide, and hyaluronic acid. The protein nanodrug demonstrated favorable stability against hydrolysis compared with free Amuc_1100. The in vivo results demonstrated that the protein nanodrug can alleviate Dox-induced cardiac toxicity by improving gut microbiota, increasing the proportion of short-chain fatty acid-producing bacteria from the Lachnospiraceae family, and further enhancing the levels of butyrate and pentanoic acids, ultimately regulating the homeostasis repair of lymphocytes in the spleen and heart. Therefore, we believe that the integrity of the intestinal barrier plays an important role in the development of chemotherapy-induced cardiotoxicity. Protective interventions targeting the intestinal barrier may hold promise as a general clinical treatment regimen for reducing Dox-induced cardiotoxicity.

Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD.

Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT.

Decrease of exosomal miR-21-5p and the increase of CD62p+ exosomes are associated with the development of sepsis in polytraumatized patients

Sepsis as a severe systemic inflammation leads oftentimes to organ dysfunction and subsequently to death. In polytrauma patients, septic complications represent with 45% the predominant cause of late death and are responsible for extremely high costs in the healthcare system. Therefore, clinicians have to detect as early as possible the begin of sepsis to improve the patient's outcome. One new promising diagnostic tool to diagnose septic complications in polytraumatized patients are exosomes.Plasma samples from polytraumatized patients (Injury Severity Score (ISS) ≥16) which developed sepsis (n = 10) and without sepsis (n = 10), were collected at emergency room (ER), 24h and 5 days after trauma. The EVs subpopulations were investigated by a bead-based multiplex flow cytometry measurement of surface epitopes and were compared with plasma EVs from healthy controls (n = 10). Moreover, exosomal cytokine concentrations were measured via high-sensitive ELISA and were correlated with systemic concentrations. For miRNA cargo analysis, we analysed the miRNAs miR-1298-5p, miR-1262, miR-125b-5p, miR-92a-3p, miR-93-5p, miR-155-5p and miR-21-5p and compared their exosomal concentrations by means of RT-qPCR.CD62p + exosomes were significantly increased in septic polytrauma-patients (p ≤ 0.05), while CD40+exosomes, as well as CD49e + exosomes were diminished (p ≤ 0.05). Furthermore, we observed that the exosomal IL-6 concentration reflects the systemic IL-6 concentration (r2 = 0.63) and did not significantly alter between patients with and without sepsis. The exosomal IL-10 concentration seemed to be constant in all patients and healthy controls. We observed that a decrease of miR-21-5p in exosomes was associated with the development of sepsis (p ≤ 0.05), while exosomal miR-93-5p, miR-155-5p and miR-92a-3p were not specifically altered in septic patients.Taken together, the present study in polytraumatized patients demonstrated that the development of sepsis is associated with an increase of CD62p + exosomes. Furthermore, the exosomal cargo was changed in septic patients: miR-21-5p was diminished.

Adjunctive hemoperfusion with Resin Hemoadsorption (HA) 330 cartridges improves outcomes in patients sustaining multiple Blunt Trauma: a prospective, quasi-experimental study

BackgroundMulti-organ dysfunction syndrome and multi-organ failure are the leading causes of late death in patients sustaining severe blunt trauma. So far, there is no established protocol to mitigate these sequelae. This study assessed the effect of hemoperfusion using resin-hemoadsorption 330 (HA330) cartridges on mortality and complications such as acute respiratory distress syndrome (ARDS) and systemic inflammatory response syndrome (SIRS) among such patients.MethodsThis quasi-experimental study recruited patients ≥ 15 years of age with blunt trauma, injury severity score (ISS) ≥ 15, or initial clinical presentation consistent with SIRS. They were divided into two groups: the Control group received only conventional acute care, while the case group received adjunctive hemoperfusion. P-values less than 0.05 were statistically significant.ResultsTwenty-five patients were included (Control and Case groups: 13 and 12 patients). The presenting vital signs, demographic and injury-related features (except for thoracic injury severity) were similar (p > 0.05). The Case group experienced significantly more severe thoracic injuries than the Control group (Thoracic AIS, median [IQR]: 3 [2–4] vs. 2 [0–2], p = 0.01). Eleven and twelve patients in the Case group had ARDS and SIRS before the hemoperfusion, respectively, and these complications were decreased considerably after hemoperfusion. Meanwhile, the frequency of ARDS and SIRS did not decrease in the Control group. Hemoperfusion significantly reduced the mortality rate in the Case group compared to the Control group (three vs. nine patients, p = 0.027).ConclusionsAdjunctive Hemoperfusion using an HA330 cartridge decreases morbidity and improves outcomes in patients suffering from severe blunt trauma.

Incidence of multiple organ failure in adult polytrauma patients: A systematic review and meta-analysis.

Postinjury multiple organ failure (MOF) is the leading cause of late death in trauma patients. Although MOF was first described 50 years ago, its definition, epidemiology, and change in incidence over time are poorly understood. We aimed to describe the incidence of MOF in the context of different MOF definitions, study inclusion criteria, and its change over time. Cochrane Library, EMBASE, MEDLINE, PubMed, and Web of Science databases were searched for articles published between 1977 and 2022 in English and German. Random-effects meta-analysis was performed when applicable. The search returned 11,440 results, of which 842 full-text articles were screened. Multiple organ failure incidence was reported in 284 studies that used 11 unique inclusion criteria and 40 MOF definitions. One hundred six studies published from 1992 to 2022 were included. Weighted MOF incidence by publication year fluctuated from 11% to 56% without significant decrease over time. Multiple organ failure was defined using four scoring systems (Denver, Goris, Marshall, Sequential Organ Failure Assessment [SOFA]) and 10 different cutoff values. Overall, 351,942 trauma patients were included, of whom 82,971 (24%) developed MOF. The weighted incidences of MOF from meta-analysis of 30 eligible studies were as follows: 14.7% (95% confidence interval [CI], 12.1-17.2%) in Denver score >3, 12.7% (95% CI, 9.3-16.1%) in Denver score >3 with blunt injuries only, 28.6% (95% CI, 12-45.1%) in Denver score >8, 25.6% (95% CI, 10.4-40.7%) in Goris score >4, 29.9% (95% CI, 14.9-45%) in Marshall score >5, 20.3% (95% CI, 9.4-31.2%) in Marshall score >5 with blunt injuries only, 38.6% (95% CI, 33-44.3%) in SOFA score >3, 55.1% (95% CI, 49.7-60.5%) in SOFA score >3 with blunt injuries only, and 34.8% (95% CI, 28.7-40.8%) in SOFA score >5. The incidence of postinjury MOF varies largely because of lack of a consensus definition and study population. Until an international consensus is reached, further research will be hindered. Systematic Review and Meta-analysis; Level III.

Changes over time in the causes of death with a functioning graft in kidney transplantation recipients

IntroductionDeath with a functioning graft (DWFG) is the most frequent cause of loss of kidney transplantation (KT). ObjectiveTo analyze the evolution of the causes of DWFG and the frequency of the types of cancer causing DWFG. MethodsRetrospective study of KT in Andalusia from 1984 to 2018. We analyzed the evolution according to eras (1984–1995; 1996–2007; 2008–2018) and according to post-transplant period (early death: first year post-KT; late death: after first year post-KT). ResultsA total of 9905 KT were performed, registering 1861 DWFG. The most frequent causes were cardiovascular disease (25.1%), infections (21.5%) and cancer (19.9%).In early death we did not observe changes, and infections were always the main cause. In late death, cardiovascular death decreased (1984−1995: 35.2%, 1996−2007: 22.6%, 2008−2018: 23.9%), but infections (1984−1995: 12.5%, 1996−2007: 18.3%, 2008−2018: 19.9%) and, above all, cancer-related deaths increased (1984−1995: 21.8%, 1996–2007: 29%, 2008−2018: 26.8%) (P < .001). In the multivariable analysis for late death due to cardiovascular disease, recipient age, retransplantation, diabetes, and the first period were risk factors, while the risk of late death due to cancer and infections was associated with recent eras.In the first year after transplantation, the most frequent neoplasia causing DWFG was post-transplant lymphoproliferative disease, and after the first year, it was lung cancer, without differences when it was analyzed by eras. ConclusionsDespite the greater comorbidity of the recipients, cardiovascular deaths have decreased. Cancer has been the main cause of late death in recent years. Lung cancer is the most frequent malignancy that causes DWFG in our transplant patients.

The correlation between hemostatic blood parameters and sepsis in patients with gunshot wounds referred to a training and research hospital.

War injuries are different among the causes of trauma compared to cases in normal life. Patients with multi-trauma due to war injury are prone to develop infective complications such as sepsis or septic shock. Septic complications are one of the leading causes of late death in multi-trauma patients. Prompt, appropriate, and effective management of sepsis has been shown to prevent multiorgan dysfunction and improve mortality and clinical outcomes. However, there is no ideal biomarker to predict sepsis. The aim of this study was to determine whether there is a correlation between hemostatic blood parameters and sepsis in patients with gunshot wounds (GSW). This descriptive study was conducted as a retrospective analysis of patients who were referred to the adult emergency department of a training and research hospital between October 1, 2016, and December 31, 2017, with a diagnosis of GSW and who developed sepsis (n=56) and did not develop sepsis (n=56) during follow-up. Demographic data such as age, sex, and blood parameters obtained from the hospital information system in the emergency department were recorded for each case. The statistical difference in hemostatic blood parameters between the two groups with and without sepsis was evaluated with Statistical Package for the Social Sciences 20.0 program. The mean age of the patients was 26.9±6.67. All of the patients were male. Of the patients who developed sepsis, 57% (n=32) were injured with improvised explosive devices (IEDs), 30% (n=17) were injured with firearms and when the anatomical injury sites were analyzed, 64% (n=36) had multiple injuries. In patients who did not develop sepsis, 48% (n=27) had IED, 43% (n=24) had GSW and 48% (n=27) had multiple injuries and 32% (n=18) had extremity injuries. Among the hemostatic blood parameters, platelet count (PLT), PTZ, INR, and Ca values showed a statistically significant difference between patients with and without sepsis, and when analyzed with the receiver operating characteristics curve, PTZ and INR showed the best diagnostic performance compared to the tested values. Increased PTZ and INR values and decreased Ca and PLT values in patients with GSW may alert clinicians to sepsis and direct them to initiate or change antibiotic therapy.

Effect of Folic Acid Treatment for Patients with Traumatic Brain Injury (TBI)-Related Hospital Acquired Pneumonia (HAP): A Retrospective Cohort Study.

Hospital Acquired Pneumonia (HAP) is one of the most common complications and late causes of death in TBI patients. Targeted prevention and treatment of HAP are of great significance for improving the prognosis of TBI patients. In the previous clinical observation, we found that folic acid treatment for TBI patients has a good effect on preventing and treating HAP. We conducted this retrospective cohort study to demonstrate what we observed by selecting 293 TBI patients from two medical centers and analyzing their hospitalization data. The result showed that the incidence of HAP was significantly lower in TBI patients who received folic acid treatment (44.1% vs. 63.0%, p = 0.012). Multivariate logistic regression analysis showed that folic acid treatment was an independent protective factor for the occurrence of HAP in TBI patients (OR = 0.418, p = 0.031), especially in high-risk groups of HAP, such as the old (OR: 1.356 vs. 2.889), ICU (OR: 1.775 vs. 5.996) and severe TBI (OR: 0.975 vs. 5.424) patients. At the same time, cohort studies of HAP patients showed that folic acid also had a good effect on delaying the progression of HAP, such as reducing the chance of tracheotomy (26.1% vs. 50.8%, p = 0.041), and reduced the length of hospital stay (15 d vs. 19 d, p = 0.029) and ICU stay (5 d vs. 8 d, p = 0.046). Therefore, we believe that folic acid treatment in TBI patients has the potential for preventing and treating HAP, and it is worthy of further clinical research.

Antineoplastic chemotherapy and immunosuppression in liver transplant recipients: Squaring the circle?

Malignancies are a major cause of late death after liver transplantation (LT). In LT recipients presenting a malignancy, antineoplastic chemotherapy is central part of the therapeutic arsenal, but management of both immunosuppressive and antineoplastic chemotherapy can be very challenging. The aim of the present retrospective study was to describe a recent single center cohort of LT recipients treated with antineoplastic cytotoxic chemotherapy. All LT recipients who received antineoplastic chemotherapy in our center between 2005 and 2021 were included. The study population included 72 antineoplastic chemotherapy courses in 69 patients. There was a majority of men (81.9%); median age at LT was 54.9 (range 1-68) and was 63.0 (18-79) at the diagnosis of malignancy. Lung carcinomas (23.6%), head and neck carcinomas (20.8%), lymphomas (16.7%), and recurrent hepatocellular carcinoma (HCC) (8.3%) were the most frequent malignancies. Neoadjuvant (30.6%), adjuvant (12.5%) or palliative (54.2%) chemotherapy was performed. Immunosuppressive regimen was modified from a calcineurin inhibitor (CNI)-based to an everolimus-based regimen (63.5% of CNI discontinuation). Median survival after diagnosis of malignancy was 22.5 months and 5-year survival was 30.1%. Chemotherapy regimen was considered optimal in 81.9% of the cases. Multivariate analysis disclosed that non-PTLD N+ stage malignancy (HR=5.52 95%CI [1.40;21.69], p=.014), non-PTLD M+ stage malignancy (HR=10.55 95%CI [3.20;34.73], p=.0001), and suboptimal chemotherapy (HR=2.73 95%CI [1.34;5.56], p=.005) were significantly associated with poorer prognosis. No rejection episode occurred during chemotherapy. The present study is the first one focused on antineoplastic chemotherapy in LT recipients. Our results suggest that immunosuppressive drugs and antineoplastic chemotherapy can be managed satisfactorily in most cases but this needs confirmation from larger cohorts.

Methanol Poisoning: An Autopsy-Based Study at the Tertiary Care Center of Uttarakhand, India.

Aims and objectiveThis study describes postmortem and histopathological findings to understand the internal progression of methanol poisoning. The study also aims to examine clinical, biochemical, and histological changes seen with methanol poisoning.Materials and methodsThe study describes the methanol poisoning tragedy that occurred in February 2019 in the Haridwar district of Uttarakhand. Ninety-one patients were admitted to the hospital, four were brought dead, four died within a few hours of admission (designated as early deaths), and four died between 10 and 45 days of hospitalization (designated as late deaths). A medicolegal autopsy was performed on all 12 deaths. Gross external and internal findings were noted, and routine viscera and blood were preserved and sent to Uttarakhand's Forensic Science Laboratory (FSL) to estimate methyl alcohol. A section of the optic nerve was taken from the optic chiasma for histopathological examination. Data were collected retrospectively from records. All data were tabulated and analyzed using Microsoft Excel version 2019. The study was approved by the Institutional Ethics Committee of All India Institute of Medical Sciences (AIIMS), Rishikesh (249201), Uttarakhand, India.ResultsMethanol poisoning is a health-associated disaster in many regions of India. Autopsy, including histopathological examination, could elicit the adverse effects of methanol on different organs. Their mean age was 37.7 years (range 21-70), and 67% (n = 8) of all victims were in the age range of 30-50 years. The average methyl alcohol level reported among hospital deaths and brought dead was 116.08 mg/dl and 224.6 mg/dl, respectively. A blurred vision had been their most common complaint, identified in 75% (n = 6), followed by vomiting and abdominal pain, while 50% (n = 4) had features of respiratory insufficiency. Mean pH and bicarbonate levels among hospital deaths were 6.61 mmol/l and 6.18 mmol/l, respectively. An autopsy revealed signs of hypoxia in all cases. Internal organs were congested. Severe metabolic acidosis leading to the respiratory failure was the cause of death in early deaths. Cerebral and pulmonary edema consequent upon septicemic shock was the cause of late deaths. A case with the most extended survival duration showed cerebral edema with intracerebral hemorrhage. Cirrhotic liver, along with features of renal failure, was an additional internal finding in late deaths. Optic nerve histopathology showed no demyelination or axonal necrosis; however, mild edematous changes were evident.ConclusionsMethanol poisoning is one of the manmade disasters in the developing world. There are various adverse effects of different organs and organ systems inside the body. Timely intervention and diagnosis can save several lives. The organ-directed meticulous autopsy can help autopsy surgeons in establishing the diagnosis and thus help the judiciary in delivering justice to the sufferers.

Cambios en el tiempo de las causas de muerte con injerto funcionante en los receptores de trasplante renal

IntroductionDeath with a functioning graft (DWFG) is the most frequent cause of loss of kidney transplantation (KT). ObjectiveTo analyze the evolution of the causes of DWFG and the frequency of the types of cancer causing DWFG. MethodsRetrospective study of KT in Andalusia from 1984 to 2018. We analyzed the evolution according to eras (1984-1995; 1996-2007; 2008-2018) and according to post-transplant period (early death: first year post-KT; late death: after first year post-KT). ResultsA total of 9,905 KT were performed, registering 1,861 DWFG. The most frequent causes were cardiovascular disease (25.1%), infections (21.5%) and cancer (19.9%).In early death we did not observe changes, and infections were always the main cause. In late death, cardiovascular death decreased (1984-1995: 35.2%, 1996-2007: 22.6%, 2008-2018: 23.9%), but infections (1984-1995: 12.5%, 1996-2007: 18.3%, 2008-2018: 19.9%) and, above all, cancer-related deaths increased (1984-1995: 21.8%, 11996-2007: 29%, 2008-2018: 26.8%) (P<0.001). In the multivariable analysis for late death due to cardiovascular disease, recipient age, retransplantation, diabetes, and the first period were risk factors, while the risk of late death due to cancer and infections was associated with recent eras.In the first year after transplantation, the most frequent neoplasia causing DWFG was post-transplant lymphoproliferative disease, and after the first year, it was lung cancer, without differences when it was analyzed by eras. ConclusionsDespite the greater comorbidity of the recipients, cardiovascular deaths have decreased. Cancer has been the main cause of late death in recent years. Lung cancer is the most frequent malignancy that causes DWFG in our transplant patients.

Venous Thromboembolism in Patients with Steroid-Refractory Chronic Graft-Versus-Host Disease Receiving Synthetic Retinoid Am80

Chronic graft-versus-host disease (GVHD) remains a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation, and the treatment of chronic GVHD remains challenging. All-trans retinoic acid (ATRA), a potent vitamin A derivative, can regulate immune responses. Synthetic retinoid Am80, which shows biological activity approximately 10 times more potent than that of ATRA, directly inhibits Th1 cytokine production. We previously reported in an experimental mouse model that Am80 down-regulated both Th1 and Th17 differentiation in donor T cells, resulting in attenuation of chronic GVHD (Nishimori H. et al. Blood 2012). Based on this background, we conducted an open-labeled, multicenter phase II study of Am80 in patients with steroid-refractory chronic GVHD (Maeda Y. et al. Acta Med. Okayama. 2016). Six facilities are participating in this study. Patients take Am80 orally (4 mg/day) for 24 weeks. If any unexpected adverse events with Grade 2 or expected adverse events with Grade 3 develop, the daily dose will be decreased to 2 mg/day, 2 mg every other day, or discontinued.Eighteen patients were enrolled and 5 out of 18 (27.8%) patients experienced venous thromboembolism (VTE). Table 1 shows the patient characteristics of those developed VTEs.It is controversial whether retinoid would enhance the incidence of VTE. Only one patient reported thrombosis when Am80 orally (6 mg/m2) for 2-8 weeks was administrated to approximately 800 patients with acute promyelocytic leukemia. In this study, 5 out of 18 (27.8%) patients experienced thrombosis and the safety committee in this study has stopped the trial due to safety concerns. Recently, a meta-analysis reported the incidence of VTE in chronic GVHD was 35 % (20-54 %). Further studies are needed to confirm the causal relationship between Am80 orally (4 mg/day) for 24 weeks and VTE. And also, alternative treatment schedule in addition to anticoagulants for the prevention of VTE will be investigated in subsequent studies. [Display omitted] DisclosuresNishimori:Toko Pharmaceutical Industries: Other: Investigational drug is provided free of charge.. Maeda:Toko Pharmaceutical Industries: Other: Investigational drug is provided free of charge.

Long-term survival after Carpentier-Edwards Perimount aortic valve replacement in Western Denmark: a multi-centre observational study

BackgroundThis study describes the long-term survival, risk of reoperation and clinical outcomes of patients undergoing solitary surgical aortic valve replacement (SAVR) with a Carpentier-Edwards Perimount (CE-P) bioprosthetic in Western Denmark. The renewed interest in SAVR is based on the questioning regarding the long-term survival since new aortic replacement technique such as transcatheter aortic-valve replacement (TAVR) probably have shorter durability, why assessment of long-term survival could be a key issue for patients.MethodsFrom November 1999 to November 2013 a cohort of a total of 1604 patients with a median age of 73 years (IQR: 69–78) undergoing solitary SAVR with CE-P in Western Denmark was obtained November 2018 from the Western Danish Heart Registry (WDHR). The primary endpoint was long-term survival from all-cause mortality. Secondary endpoints were survival free from major adverse cardiovascular and cerebral events (MACCE), risk of reoperation, cause of late death, patient-prothesis mismatch, risk of AMI, stroke, pacemaker or ICD implantation and postoperative atrial fibrillation (POAF). Time-to-event analysis was performed with Kaplan-Meier curve, cumulative incidence function was performed with Nelson-Aalen cumulative hazard estimates. Cox regression was applied to detect risk factors for death and reoperation.ResultsIn-hospital mortality was 2.7% and 30-day mortality at 3.4%. The 5-, 10- and 15-year survival from all-cause mortality was 77, 52 and 24%, respectively. Survival without MACCE was 80% after 10 years. Significant risk factors of mortality were small valves, smoking and EuroSCORE II ≥4%. The risk of reoperation was < 5% after 7.5 years and significant risk factors were valve prosthesis-patient mismatch and EuroSCORE II ≥4%.ConclusionsPatients undergoing aortic valve replacement with a Carpentier-Edwards Perimount valve shows a very satisfying long-term survival. Future research should aim to investigate biological valves long-term durability for comparison of different SAVR to different TAVR in long perspective.

Limited vs. extended repair for acute type I aortic dissection: long-term outcomes over a decade in Beijing Anzhen Hospital.

Limited vs. extended repair for acute type I aortic dissection: long-term outcomes over a decade in Beijing Anzhen Hospital.

ADENOCARCINOMA DE OVÁRIO EM PÓS-OPERATÓRIO TARDIO DE TRANSPLANTE HEPÁTICO: RELATO DE CASO

It is known that transplanted patients are at higher risk of developing malignant neoplasia. This fact is mainly due to the use of immunosuppressive drugs. We report the case of NAF, 38 years old, submitted to orthotopic liver transplantation in February, 1998, due to liver cirrhosis caused by hepatitis C virus. The investigation showed pelvic expansive lesion measuring 12.5x 9.0x 8.3 cm in contact with uterine wall. Ovary tumor whose freezing biopsy showed undifferentiated malignancy for an ovary laparotomy was chosen. Panhysterectomy and left oophorectomy were carried out, and histopathological specimen evidenced clear cell ovary adenocarcinoma, stage IA. Patient in follow-up for 3 and half years, with no evidence of recurrence and tumor markers within the normal range. The development of post-transplant neoplasms is a frequent complication and it is one of the main causes of late death in these patients. Avoiding excessive immunosuppression is the main recommendation although the prevalence was low the following laboratorial biomarker for tumor can be performed.

Diagnosing Preclinical Cardiac Dysfunction in Swiss Childhood Cancer Survivors: Protocol for a Single-Center Cohort Study.

BackgroundCardiovascular disease is the leading nonmalignant cause of late deaths in childhood cancer survivors. Cardiovascular disease and cardiac dysfunction can remain asymptomatic for many years, but eventually lead to progressive disease with high morbidity and mortality. Early detection and intervention are therefore crucial to improve outcomes.ObjectiveIn our study, we aim to assess the prevalence of preclinical cardiac dysfunction in adult childhood cancer survivors using conventional and speckle tracking echocardiography; determine the association between cardiac dysfunction and treatment-related risk factors (anthracyclines, alkylating agents, steroids, cardiac radiation) and modifiable cardiovascular risk factors (abdominal obesity, hypertension); investigate the development of cardiac dysfunction longitudinally in a defined cohort; study the association between cardiac dysfunction and other health outcomes like pulmonary disease, endocrine disease, renal disease, quality of life, fatigue, strength and endurance, and physical activity; and gain experience conducting a clinical study of childhood cancer survivors that will be extended to a national, multicenter study of cardiac complications.MethodsFor this retrospective cohort study, we will invite ≥5-year childhood cancer survivors who were treated at the University Children's Hospital Bern, Switzerland with any chemotherapy or cardiac radiation since 1976 and who are ≥18 years of age at the time of the study for a cardiac assessment at the University Hospital Bern. This includes 544 childhood cancer survivors, of whom about half were treated with anthracyclines and/or cardiac radiation and half with any other chemotherapy. The standardized cardiac assessment includes a medical history focusing on signs of cardiovascular disease and its risk factors, a physical examination, anthropometry, vital parameters, the 1-minute sit-to-stand test, and echocardiography including 2-dimensional speckle tracking.ResultsWe will invite 544 eligible childhood cancer survivors (median age at the time of the study, 32.5 years; median length of time since diagnosis, 25.0 years) for a cardiac assessment. Of these survivors, 300 (55%) are at high risk, and 244 (45%) are at standard risk of cardiac dysfunction.ConclusionsThis study will determine the prevalence of preclinical cardiac dysfunction in Swiss childhood cancer survivors, inform whether speckle tracking echocardiography is more sensitive to cardiac dysfunction than conventional echocardiography, and give a detailed picture of risk factors for cardiac dysfunction. The results will help improve primary treatment and follow-up care of children with cancer.Trial RegistrationClinicalTrials.gov NCT03790943; https://clinicaltrials.gov/ct2/show/NCT03790943International Registered Report Identifier (IRRID)DERR1-10.2196/17724

Causes of late mortality among ICU-treated patients with sepsis.

Patients with sepsis may have an increased risk of late mortality, but the causes of late death are unclear. This retrospective matched cohort study aimed to determine the causes of late death (≥1year) among patients with sepsis compared to patients without sepsis. 8760 patients with severe sepsis or septic shock (2001 consensus criteria) registered in the Swedish Intensive Care Registry (2008-2013) were compared with a 1:1 matched (gender, age, SAPS3 probability for death, ICU length of stay) control group consisting of non-septic ICU patients. Causes of death (International Classification of Diseases codes) were obtained from the Swedish Cause of Death Register (2008-2014). During 2008-2014, 903 patients with sepsis died at≥365days after their initial septic event, compared to 884 patients in the control group. Median time of follow-up was 313days (sepsis group, interquartile range 11-838days) vs 288days (control group, 9-836days). The most common causes of death were heart diseases (sepsis: 50.2%, non-septic: 48.6%) and cancer (sepsis: 33.7%, non-septic: 31.7%). Infectious diseases were significantly more common cause of death in the sepsis group (24.3% vs 19.6%, respectively; P<.05). Pneumonia was a common infectious cause of death in both groups, whereas sepsis was more common in the sepsis group. The most common causes of late death after ICU admission among patients with and without sepsis were heart diseases and cancer. However, patients with sepsis more frequently had infectious diseases as a cause of late death, compared to non-septic patients.

NanoString Gene Expression Profiling in Chronic Lung Allograft Dysfunction (CLAD)

CLAD, mainly manifest as bronchiolitis obliterans syndrome (BOS), is the leading cause of late death in lung recipients. BOS develops despite routine immunosuppression and its pathogenesis is poorly understood. The histological correlate of BOS is bronchiolitis obliterans (BO), or airways fibrosis. We quantified over 700 immune-related genes in BO affected airways to better understand immune responses active in end-stage BOS. Formalin fixed paraffin embedded lung tissue was procured at retransplantation for BOS (n=6). Unused donor tissue was used as normal control (n=5). Histologies of interest were isolated using laser capture microdissection (LCMD). Within each BOS lung, airways histologically affected by BO pathology, defined as intraluminal fibrous expansion, were isolated. Additionally, airways unaffected by evident fibrosis were isolated. Within each donor lung, histologically normal airways were isolated. Cellular RNA was extracted and multiplex gene expression analysis was performed using the NanoString PanCancer Immune Profiling Panel. Linear regression was used to compare gene expression among groups. The primary comparison was differential expression in BO affected vs. normal donor airways. We also compared expression in BO affected vs. unaffected airways within BOS explant lungs. P-values were corrected for multiple comparisons using Benjamini-Hochberg. Sixty-seven genes were significantly different between BO affected vs. normal donor airways, of which 52 had a fold change (FC) <0.5 or >2. Along with genes in adaptive immunity, several genes related to innate and humoral activation were significantly increased in BO affected airways. Among the innate immune genes with increased expression in BO were toll-like receptor 1 (FC 2.31) and its adaptor molecule CD14 (FC 5.26) in addition to the complement subcomponent C1s (FC 3.06), while those in humoral immunity included bone marrow stromal antigen 2 (FC 3.41), important to the growth and development of B-cells. No genes were significantly differentially expressed between BO affected vs. unaffected airways within BOS explant lungs. Our results suggest innate and humoral immune responses are active in airways affected by BO pathology, and also in airways without evident fibrosis. Ongoing analyses of BO lesions through LCMD will provide new insights into CLAD pathogenesis.

AIUM Practice Parameter for the Performance of an Ultrasound Examination of Solid-Organ Transplants.

AIUM Practice Parameter for the Performance of an Ultrasound Examination of Solid-Organ Transplants.