Coeliac disease and risk of tuberculosis: a population based cohort study

BACKGROUND: Coeliac disease (CD) is an autoimmune disease often characterised by malnutrition and linked to a number of complications such as an increased risk of lymphoma, adverse pregnancy outcome, and other autoimmune diseases. Tuberculosis (TB) affects a large proportion of the world population and is more common in individuals with malnutrition. We investigated the risk of TB in 14 335 individuals with CD and 69 888 matched reference individuals in a general population based cohort study. METHODS: Cox proportional hazards method was used to calculate the risk of subsequent TB in individuals with CD. In a separate analysis, the risk of CD in individuals with prior TB was calculated using conditional logistic regression. RESULTS: CD was associated with an increased risk of subsequent TB (hazard ratio (HR) 3.74, 95% CI 2.14 to 6.53; p < 0.001). Similar risk estimates were seen when the population was stratified for sex and age at CD diagnosis. Individuals with CD were also at increased risk of TB diagnosed in departments of pulmonary medicine, infectious diseases, paediatrics, or thoracic medicine (HR 4.76, 95% CI 2.23 to 10.16; p < 0.001). The odds ratio for CD in individuals with prior TB was 2.50 (95% CI 1.75 to 3.55; p < 0.001). CONCLUSIONS: CD is associated with TB. This may be due to malabsorption and lack of vitamin D in persons with CD. Individuals with TB and gastrointestinal symptoms should be investigated for CD.     

Haemodialysis and the risk of stroke: A population-based cohort study in Taiwan, a country of high incidence of end-stage renal disease

Aims: Data regarding the occurrence of stroke in dialysis patients are limited and epidemiologic studies to date are controversial with respect to the stroke subtype among dialysis patients. The aim of this study was to perform a population‐based study with a retrospective cohort design to investigate the risk of stroke after the initiation of haemodialysis (HD) among end‐stage renal disease (ESRD) patients in Taiwan – a country with the highest incidence of ESRD in the world. Methods: Data were retrospectively obtained from the Taiwan National Health Insurance Research Database. In total, 644 patients who were beginning HD between 1999 and 2003 were recruited as the study cohort and 3220 patients matched for age and sex were included as the comparison cohort. Multivariate Cox proportional hazard regression models were used to adjust for confounding and to compare the 5 year stroke‐free survival rate between these two cohorts. Results: The incidence rate of stroke (41.76 per 1000 person‐years) was significantly higher in the HD cohort than in the control cohort (24.29 per 1000 person‐years). After adjusting for potential confounders, the adjusted hazard ratios of ischaemic stroke and haemorrhagic stroke were 2.16 (95% confidence interval = 1.57–2.97) and 3.78 (95% confidence interval = 1.90–7.55), respectively. Conclusion: We conclude that HD patients were at an increased risk for both ischaemic and haemorrhagic stroke compared with the general population.     

Graft-versus-host disease in solid organ transplantation

Abstract. Graft-versus-host disease is well recognized in bone marrow transplantation, but has only recently been described in solid organ transplantation. Two such cases in liver graft recipients, proven by the demonstration of donor type HLA antigens in the peripheral blood and marrow on tissue typing, are described in this paper. The literature on this subject is reviewed and the treatment discussed. It is postulated that there is an order of risk of development of graft-versus-host disease depending on the amount of viable lymphoid tissue included with the transplanted organ as follows: small bowel > heartlung > liver > kidney > heart. It seems likely that this condition has been substantially underdiagnosed in the past and that greater awareness of the possibility of graft-versus-host disease in solid organ recipients will lead to the recognition of further cases and allow appropriate treatment to be promptly instituted.     

Graft-versus-host disease in solid organ transplantation

Graft-versus-host disease is well recognized in bone marrow transplantation, but has only recently been described in solid organ transplantation. Two such cases in liver graft recipients, proven by the demonstration of donor type HLA antigens in the peripheral blood and marrow on tissue typing, are described in this paper. The literature on this subject is reviewed and the treatment discussed. It is postulated that there is an order of risk of development of graft-versus-host disease depending on the amount of viable lymphoid tissue included with the transplanted organ as follows: small bowel>heart-lung>liver>kidney>heart. It seems likely that this condition has been substantially underdiagnosed in the past and that greater awareness of the possibility of graft-versus-host disease in solid organ recipients will lead to the recognition of further cases and allow appropriate treatment to be promptly instituted.     

Coeliac disease and risk of renal disease-a general population cohort study.

BACKGROUND: Coeliac disease (CD) may be a risk factor for renal disease. METHODS: We investigated the risk of any form of glomerulonephritis (GN) (acute, chronic and non-specified), chronic glomerulonephritis (CGN) and renal replacement therapy including dialysis treatment and kidney transplantation (KT) in patients with CD in a general population-based cohort study. We used Cox regression to assess the risk of renal disease in 14,336 patients who had received a diagnosis of CD (1964-2003) and 69,875 reference individuals matched for age, calendar year, sex and county. Patients were identified using the Swedish Hospital Discharge Registry. Follow-up began 1 year after study entry. RESULTS: CD was associated with an increased risk of any form of GN (hazard ratio (HR) = 1.64; 95% confidence intervals (CI) = 1.01-2.66; P = 0.046; 89 events), CGN (HR = 2.65; 95% CI = 1.34-5.24; P = 0.005; 39 events), dialysis (HR = 3.48; 95% CI = 2.26-5.37; P < 0.001; 102 positive events) and KT (HR = 3.15; 95% CI = 1.29-7.71; P = 0.012; 22 events). CONCLUSION: We suggest that immune characteristics associated with CD increase the risk of chronic renal disease. Individuals with CD may also be at a moderately increased risk of any form of GN.     

Innate immunity and organ transplantation: focus on lung transplantation

Ischemia reperfusion injury (IRI) that occurs with solid organ transplantation activates the innate immune system to induce inflammation. This leads to enhanced acute allograft rejection, impaired transplant tolerance and accelerated progression of chronic rejection. In this review, we discuss the innate immune signaling pathways that have been shown to play a role in organ transplantation. In particular, we focus on Toll‐like receptor signaling pathways and how they have influenced outcomes after organ transplantation both experimentally and from clinical studies. Furthermore, we describe the substances that trigger the innate immune system after transplantation and several of the key cellular mediators of inflammation. We specifically point out unique aspects of activation of the innate immune system after lung transplantation. Finally, we discuss the areas that should be investigated in the future to more clearly understand the influence of the innate immune system after organ transplantation.     

COVID-19 in solid organ transplant recipients: A national cohort study from Sweden

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1–2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6–7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.     

New onset diabetes after kidney transplantation in autosomal dominant polycystic kidney disease: a retrospective cohort study

Background: New onset diabetes after transplantation (NODAT) is a common adverse outcome of organ transplantation that increases the risk of cardiovascular disease, infection and graft rejection. In kidney transplantation, apart from traditional risk factors, autosomal dominant polycystic kidney disease (ADPKD) has also been reported by several authors as a predisposing factor to the development of NODAT, but any rationale for an association between ADPKD and NODAT is unclear. We examined the cumulative incidence of NODAT in or own transplant population comparing ADPKD patients with non‐ADPKD controls. Methods: A retrospective cohort study to determine the cumulative incidence of patients developing NODAT (defined by World Health Organization‐based criteria and/or use of hypoglycaemic medication) was conducted in 79 patients with ADPKD (79 transplants) and 423 non‐ADPKD controls (426 transplants) selected from 613 sequential transplant recipients over 8 years. Patients with pre‐existing diabetes as a primary disease or comorbidity and/or with minimal follow up or early graft loss/death were excluded. Results: Of the 502 patients (505 transplants) studied, 86 (17.0%) developed NODAT. There was no significant difference in the cumulative incidence of NODAT in the ADPKD (16.5%; CI 13.6–20.7%) compared with the non‐ADPKD (17.1%; CI 8.3–24.6%) control group. Of the 13 patients in the ADPKD group with NODAT, three required treatment with insulin with or without oral hypoglycaemic agents. Among the 73 NODAT patients in the non‐ADPKD group, eight received insulin with or without oral hypoglycaemics. Furthermore, of the patients that did develop NODAT, there was no difference in the time to its development in patients with and without ADPKD Conclusion: There was no evidence of an increased incidence of NODAT in ADPKD kidney transplant recipients.     

Solid organ transplantation in survivors of hematopoietic cell transplantation: a single institution case series and literature review

Beitinjaneh A, Burns LJ, Majhail NS. Solid organ transplantation in survivors of hematopoietic cell transplantation: a single institution case series and literature review.
Clin Transplant 2010: 24: E94–E102.
© 2009 John Wiley & Sons A/S. Abstract: For selected hematopoietic cell transplant (HCT) survivors with severe organ dysfunction, solid organ transplantation (SOT) may offer the best chance for better quality of life and extended survival. However, SOT following HCT has not been well described. We report our institutional experience of SOT in 12 HCT recipients and present a review of the published literature of this procedure in HCT survivors. Our experience with transplanted organs included kidney (n = 7), lung (n = 3), liver (n = 2) and heart (n = 1). Age at HCT ranged from 2 to 56 yr. Median time between HCT and SOT was 7.9 yr (range 1.2–15.9 yr). Among the 11 patients with post‐SOT follow‐up information, 10 had normal function of the transplanted solid organ at the time of last contact or death. Infections and secondary malignancy were the most common complications. Four other institutional experiences with kidney transplant, 21 case reports of liver transplant, 11 case reports of lung transplant and one cardiac transplant are also summarized. SOT is feasible for selected HCT survivors with organ failure and may be associated with favorable long‐term survival and graft function. More research is needed to further delineate the subset of survivors who will benefit the most from SOT with the least risk of complications.     

Graft protection in organ transplantation

Preserving donor organs in optimal condition is a prerequisite for successful transplantation. The donor organ is subjected to a multitude of stresses. In this review, we will discuss the consequences of brain death on donor organs. The effects of an extended ischaemic period followed by the reperfusion necessary for the harvest, storage and implantation of transplant organs will be evaluated. As progressively more is known about the underlying pathophysiological mechanisms, focused and efficient therapeutic interventions can be developed. We will review current organ protection techniques and look at possible future strategies to further improve the final donor organ quality.     

Survival after lung transplantation in recipients with alpha‐1‐antitrypsin deficiency compared to other forms of chronic obstructive pulmonary disease: a national cohort study

Alpha‐1‐antitrypsin deficiency (AATD) is grouped with chronic obstructive pulmonary disease (COPD); however, this may not be appropriate. This study assessed whether AATD confers a different prognosis than COPD following lung transplantation. We employed the United Network for Organ Sharing (UNOS) database, grouping patients by diagnoses of AATD or COPD. Kaplan–Meier methods and Cox modeling were performed to determine the association of diagnosis and overall survival. Of 9569 patients, 1394 (14.6%) had a diagnosis of AATD. Patients with AATD who received a single‐lung transplant had reduced 1‐year survival [adjusted hazard ratio (AHR): 1.68, 95% CI: 1.26, 2.23]. Among patients who received a bilateral lung transplant, there was no significant difference in survival by diagnosis (AHR for AATD as compared to COPD: 0.96, 95% CI: 0.82, 1.12). After the implementation of the lung allocation score (LAS), there was no significant difference in survival among patients who received a single (AHR: 1.15, 95% CI: 0.69, 1.95) or bilateral (AHR: 0.99, 95% CI: 0.73, 1.34) lung transplant by diagnosis. Lung transplantation is increasingly employed in the care of the patient with COPD. Although recipients undergoing LTX for AATD are at increased risk of both acute rejection and airway dehiscence post‐transplant, in the post‐LAS era, survival rates are similar for recipients with AATD in comparison with COPD.     

Impact of metabolic syndrome on the incidence of chronic kidney disease: a Chinese cohort study

Aim: Metabolic syndrome (MetS) is a major culprit in cardiovascular disease and chronic kidney disease (CKD) in Western populations. We studied the longitudinal association between MetS and incident CKD in Chinese adults. Methods: A cohort study was conducted in a nationally representative sample of 4248 Chinese adults in Taiwan. The MetS was defined according to a unified criteria set by several major organizations and CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m². Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for sex, age, body mass index (BMI) and serum levels of total cholesterol. Results: The prevalence of MetS among participants at baseline recruitment was 15.0% (637/4248). During a median follow‐up period of 5.40 years, 208 subjects (4.9%) developed CKD. The multivariate‐adjusted HR of CKD in participants with MetS compared with those without was 1.42 (95% CI = 1.03, 1.73). Additionally, there was a significantly graded relationship between the number of the MetS components and risk of CKD. Further, the relation between MetS and incident CKD was more robust in subjects with BMI >27.5 kg/m² than in those with lower BMI. Conclusion: The results suggest that the presence of MetS was significantly associated with increased risk of incident CKD in a Chinese population. These findings warrant future studies to test the impact of preventing and treating MetS on the reduction of the occurrence of CKD.     

Clinical risk factors for osteoporotic fracture: A population‐based prospective cohort study in Korea

Clinical risk factors (CRFs), either alone or in combination with bone mineral density, are used to determine the fracture risk for clinical assessment and to determine intervention thresholds. Because fracture risk is strongly affected by ethnicity and population‐specific differences, we sought to identify Korean‐specific CRFs for fracture, in combination with quantitative ultrasound (qUS) measurements of the radius and tibia. A total of 9351 subjects (4732 men and 4619 women) aged 40 to 69 years were followed for a mean of 46.3 ± 2.2 months. We obtained CRF information using a standardized questionnaire and measured anthropometric variables. Speed of sound at the radius (SoSR) and tibia (SoST) were measured by qUS. Fracture events were recorded using a questionnaire, and a height‐loss threshold was used as an indicator of vertebral fracture. Relative risks were calculated by Cox regression analysis. A total of 195 subjects (61 men and 134 women) suffered low‐trauma fractures. Older age, lower body mass index (BMI), and previous fracture history were positively associated with fracture risk in both sexes. Decreased hip circumference, lack of regular exercise, higher alcohol intake, menopause, and osteoarthritis history were further independent CRFs for fracture in women. However, neither SoSR nor SoST was independently associated with fracture risk. In this study, we identified the major Korean‐specific CRFs for fracture and found that smaller hip circumference was a novel risk factor. This information will allow optimal risk‐assessment targeting Koreans for whom treatment would provide the greatest benefit. © 2010 American Society for Bone and Mineral Research     

Increasing incidence of melanoma after solid organ transplantation: a retrospective epidemiological study

The risk of melanoma in organ transplant recipients (OTR) is increased compared with the general population. This retrospective study registered all cases of post‐transplant melanoma in kidney, heart, lung, and liver transplant recipients followed in our specialized post‐transplant Dermatology Clinic since 1991. The yearly prevalence of melanoma and skin carcinoma between 2000 and 2015 was computed and compared in this population. Based on another cohort of kidney transplant recipients grafted since 2005, adjusted age‐ and sex‐standardized incidence ratio (SIR) was calculated using a renal transplantation registry. In our overall OTR cohort, between 1991 and 2000, five melanomas occurred in 1800 OTRs (0.28%), whereas between 1991 and 2015, 53 melanomas were diagnosed in 49 of 4510 OTR (1.09%), representing a 3.9‐fold increase in prevalence after 2000. Remarkably, the prevalence of nonmelanoma skin cancers remained unchanged over this period. Two deaths related to melanoma were recorded with an overall follow‐up of 62 months. In our cohort of 1102 renal transplant recipients, the SIR of melanoma was 4.52. Our data suggest that contrasting with nonmelanoma skin cancer, the risk of post‐transplant melanoma has considerably increased over the last decade.     

Ischemic preconditioning in solid organ transplantation: from experimental to clinics

This study reviews the current understanding of ischemic preconditioning (IP) in experimental and clinical setting, and the mechanisms that mediate the complex processes involved as a tool to protect against ischemia and reperfusion (I/R) injury, but is not intended as a complete literature review of preconditioning. IP has been mainly elucidated in cardiac ischemia. Recent reports confirm the efficacy of pre- and postconditioning in cardiac surgery and percutaneous coronary interventions in humans. IP utilizes endogenous as well as distant mechanisms in skeletal muscle, liver, lung, kidney, intestine and brain in animal models to convey varying degrees of protection from I/R injury. Specifically, preconditioned tissues exhibit altered energy metabolism, better electrolyte homeostasis and genetic reorganization, as well as less oxygen-free radicals and activated neutrophils release, reduced apoptosis and better microcirculatory perfusion. To date, there are few human studies, but recent trials suggest that human liver, lung and skeletal muscle acquire protection after IP. Present data address the potential therapeutic application of IP in the prevention of I/R damage specially aimed at clinical transplantation. IP is ubiquitous but more research is required to fully translate these findings to the clinical arena.     

Ethical issues in organ transplantation

Critical care clinicians are central to the organ transplantation process and therefore should be aware of the myriad ethical issues it raises. Organ donation can transform the lives of transplant recipients. However, it also warrants particular ethical scrutiny. Organ procurement is a procedure that cannot physically benefit the patient upon whom it is performed. Moreover, the potential donor incapacitated by terminal illness is usually unable to actively consent to donation. This article reviews contemporary debates in vital organ transplantation, including the definition of death, perimortem interventions and research, and merits of ‘opt-in’ versus ‘opt-out’ donor registries.