Prevalence of Immunosuppression Among US Adults.

This analysis presents population prevalence estimates of immunosuppression among US adults using data from the 2021 National Health Interview Survey.

Low risk of bacterial co-infection, opportunistic diseases, and persistent immunosuppression in people living with HIV and COVID-19.

PURPOSE: SARS-CoV-2 infection produces lymphopenia and CD4+ T-cell decrease, which could lead to a higher risk of bacterial co-infection or impair immunological evolution in people living with HIV (PLWH). METHODS: We investigated the rate of co-infection and superinfection, and the evolution of CD4+ count and CD4+/CD8+ ratio, in hospitalized PLWH with COVID-19. RESULTS: From March to December 2020, 176 PLWH had symptomatic COVID-19 and 62 required hospitalization (median age, 56 years, 89% males). At admission, 7% and 13% of patients had leukocytosis or increased procalcitonin values and 37 (60%) received empiric antibiotic therapy, but no bacterial co-infection was diagnosed. There were seven cases of superinfection (12%), and one case of P. jiroveci pneumonia during ICU stay. No significant change in CD4+ count or CD4+/CD8+ ratio was observed after discharge. CONCLUSION: Bacterial co-infection is not frequent in PLWH with COVID-19. Immune recovery is observed in most of patients after the disease.

Evaluating the effects of Cyclosporine A immunosuppression on Mycobacterial infection by inhaling of Cyclosporine A administrated BALB/c mice with live Bacillus Calmette Guérin.

Cyclosporine A (CsA) is an immunosuppressive drug used in organ transplantation and treatment of autoimmune diseases. Effects of CsA on determining the direction of the immune response and pathogenesis of infections by altering immune responses particulary T cells functions have always been questionable. We evaluated the effect of different doses of CsA on course of infection in BALB/c mice infected with live Bacillus Calmette Guérin (BCG) (as an example of Mycobacterial infections). Four groups of mice (n = 5) receiving 5, 25, 125, and 0 mg/kg of CsA, three times a week, were infected with BCG aerosolly. Before BCG inhalation and 40-/60- days post-infection, cell proliferation and CD4+CD25+ cell percentage were evaluated in splenocytes of mice after culture and stimulation with PHA or BCG lysate. The histopathological alterations and bacterial burden were assessed in lung tissue. Cells showed a dose-dependent decrease in proliferation and the percentage of CD4+ CD25+ cells. After BCG infection, in presence of dose 125 mg/kg, there were some exceptions. The number of bacteria and histopathological lesions and inflammation in lung tissues increased in a dose-dependent manner. CsA immunosuppressed BCG infected mice can be used as a safe model for studying Mycobacterium species pathogenesis and related cellular immune responses.

Consequences of the first and second COVID-19 wave on kidney transplant recipients at a large Indian transplant centre.

BACKGROUND: There is a scarcity of data comparing the consequences of first and second COVID-19 waves on kidney transplant recipients (KTRs) in India. METHODS: We conducted a single-centre retrospective study of 259 KTRs with COVID-19 to compare first wave (March 15-December 31 2020, n = 157) and second wave (April 1-May 31 2021, n = 102). RESULTS: KTRs during second wave were younger (43 vs. 40 years; p-value .04) and also included paediatric patients (0 vs. 5.9%; p-value .003). Symptoms were milder during the second wave (45 vs. 62.7%; p-value .007); COVID-19 positive patients had less frequent cough (32 vs. 13.8%; p-value .001), fever was less frequent (58 vs. 37%; p-value .001), and we observed fewer co-morbidities (11 vs. 20.6%; p-value .04). The percentages of neutrophils (77 vs. 83%; p-value .001) and serum ferritin (439 vs. 688; p-value .0006) were higher during second wave, while lymphocyte counts were reduced (20 vs. 14%; p-value .0001). Hydroxychloroquine (11 vs. 0%; p-value .0001) and tocilizumab (7 vs. 0%; p-value .004) were more frequently prescribed during first wave, while utilization of dexamethasone (6 vs. 27%; p-value .0001) and remdesivir (47 vs. 65%; p-value .03) increased during the second wave. Mucormycosis (1.3 vs. 10%; p-value .01) and ICU admissions (20 vs. 37.2%; p-value .002) were more frequent during second wave. The 28-day mortality rate (9.6 vs. 10%; p-value 1) was not different. CONCLUSIONS: There has been a different clinical spectrum of COVID-19 amongst KTR with similar mortality between the two waves at a large Indian transplant centre.

Immunosuppression and COVID-19 infection in British Columbia: Protocol for a linkage study of population-based administrative and self-reported survey data.

INTRODUCTION: Cases of the novel coronavirus disease (COVID-19) continue to spread around the world even one year after the declaration of a global pandemic. Those with weakened immune systems, due to immunosuppressive medications or disease, may be at higher risk of COVID-19. This includes individuals with autoimmune diseases, cancer, transplants, and dialysis patients. Assessing the risk and outcomes of COVID-19 in this population has been challenging. While administrative databases provide data with minimal selection and recall bias, clinical and behavioral data is lacking. To address this, we are collecting self-reported survey data from a randomly selected subsample with and without COVID-19, which will be linked to administrative health data, to better quantify the risk of COVID-19 infection associated with immunosuppression. METHODS AND ANALYSIS: Using administrative and laboratory data from British Columbia (BC), Canada, we established a population-based case-control study of all individuals who tested positive for SARS-CoV-2. Each case was matched to 40 randomly selected individuals from two control groups: individuals who tested negative for SARS-CoV-2 (i.e., negative controls) and untested individuals from the general population (i.e., untested controls). We will contact 1000 individuals from each group to complete a survey co-designed with patient partners. A conditional logistic regression model will adjust for potential confounders and effect modifiers. We will examine the odds of COVID-19 infection according to immunosuppressive medication or disease type. To adjust for relevant confounders and effect modifiers not available in administrative data, the survey will include questions on behavioural variables that influence probability of being tested, acquiring COVID-19, and experiencing severe outcomes. ETHICS AND DISSEMINATION: This study has received approval from the University of British Columbia Clinical Research Ethics Board [H20-01914]. Findings will be disseminated through scientific conferences, open access peer-reviewed journals, COVID-19 research repositories and dissemination channels used by our patient partners.

Clinical Features and Outcomes of Combined Pulmonary Fibrosis and Emphysema After Lung Transplantation.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is recognized as a characteristic syndrome of smoking-related interstitial lung disease that has a worse prognosis than idiopathic pulmonary fibrosis (IPF). However, outcomes after lung transplantation for CPFE have not been reported. The aim of this study is to describe the clinical features and outcomes of CPFE after lung transplantation. RESEARCH QUESTION: What are the clinical features and outcomes of CPFE after lung transplantation? STUDY DESIGN AND METHODS: This is a single-center retrospective cohort study of patients with CPFE and IPF who underwent lung transplantation at our center between January 2011 and December 2016. We defined CPFE as ≥10% emphysema in the upper lung fields combined with fibrosis on high-resolution CT scan. We characterized the clinical features of patients with CPFE and compared their outcomes after lung transplantation with those with IPF. RESULTS: Twenty-seven of 172 (16%) patients with IPF met criteria for CPFE. Severe pulmonary hypertension was present in 16 of 27 (59%) patients with CPFE. On logistic regression analysis, CPFE was significantly associated with primary graft dysfunction (PGD) grade 3 (OR, 3.14; 95% CI, 1.18-8.37; P = .02). On competing risk regression analysis, CPFE was associated with acute cellular rejection (ACR) grade ≥ A2, and chronic lung allograft dysfunction (CLAD) (hazard ratio [HR], 1.89; 95% CI, 1.10-3.25; P = .02; HR, 1.96; 95% CI, 1.02-3.77; P = .04, respectively). Five-year survival was 79.0% for the CPFE group and 75.4% for the IPF group (log-rank P = .684). INTERPRETATION: After transplantation, patients with CPFE were more likely to develop PGD, ACR, and CLAD compared with those with IPF. However, survival was not significantly different between the two groups.

Prior immunosuppressive therapy is associated with mortality in COVID-19 patients: A retrospective study of 835 patients.

Though it is widely believed that chronic immunosuppressive medications increase the severity of coronavirus disease 2019 (COVID-19) illness, there is little data to support this. We performed a retrospective study of COVID-19 positive patients diagnosed at a single academic medical center between March 10, 2020 and October 13, 2020. A total of 835 patients diagnosed with COVID-19 by polymerase chain reaction were included (median age 64 years; 52% female). Of these, 46 (5.5%) had a prescription for an immunosuppressive therapy before diagnosis, most commonly oral steroids (20, 43%), mycophenolate (12, 26%), or tacrolimus (11, 24%). Patients on immunosuppressive therapy with COVID-19 had increased mortality (30% vs. 17%, p = 0.036; odds ratio 2.1, 95% confidence interval 1.11-4.04), which remained significant (p = 0.040) after performing multivariate logistic regression controlling for gender, age, race, and comorbidity status. Laboratory markers of inflammation were uniformly elevated in both patients on or not on immunosuppressive therapies who died, but lymphocytes and neutrophils were decreased in both COVID-19 patients on immunosuppressive therapies who died and who remained alive. These findings demonstrate that COVID-19 disease is more severe in patients taking prior immunosuppressive medications. This finding emphasizes the need for aggressive monitoring and supportive care for immunosuppressed patients who are diagnosed with COVID-19.

Variation in immunosuppression practices among pediatric liver transplant centers-Society of Pediatric Liver Transplantation survey results.

BACKGROUND: Variation in IS exists among pediatric liver transplant centers. While individual centers may publish their practice paradigms, current data on practices as a whole are lacking. This study sought to ascertain the IS protocols of pediatric liver transplant centers within the SPLIT to better understand variability and similarities among peer institutions. METHODS: A 27-item questionnaire was developed within the SPLIT Quality Improvement and Clinical Care Committee. The survey collected data regarding center demographics, IS practices, and treatment of acute cellular rejection. RESULTS: Twenty-eight (64%) SPLIT centers responded with 22 (79%) centers performing more than 10 transplants per year and 17 (61%) following more than 100 post-transplant recipients. All centers use a written protocol, and 25 (89%) have a dedicated transplant pharmacist/PharmD. Twenty-five (89%) centers use steroids for induction alone or in combination with thymoglobulin/interleukin-2 antibodies. All centers use tacrolimus for initial maintenance therapy. Most centers have specialized protocols for ABO-incompatible transplants, recipients with renal dysfunction, autoimmune liver diseases, and liver tumors. Treatment of rejection varied but was associated with escalation in IS. CONCLUSION: IS practices among pediatric liver transplant centers are similar including the use of written protocols, pharmacy involvement, steroids for induction, tacrolimus as initial IS, tacrolimus reduction/delay for renal dysfunction, and escalation of IS with rejection severity. However, other IS practices show wide variability including treatment for ABO-incompatible grafts and presumed rejection. This study serves as a foundation to guide prospective research linking IS practice to outcomes to determine best practice.

Induction Immunosuppression and Renal Outcomes in Adult Heart Transplantation.

BACKGROUND: This study explores the use of induction therapy in orthotopic heart transplantation as it relates to preoperative renal function and evaluates the impact of its utilization on post-transplant outcomes. METHODS: We conducted a retrospective analysis using the United Network for Organ Sharing database from 2000 to 2018 evaluating the initiation of de novo dialysis after transplantation. We examined the relationship between induction immunosuppression and pre-transplant estimated glomerular filtration rate with post-transplant outcomes, accounting for inter-center variability through a mixed-effects logistic regression model. RESULTS: In total, 16,201 patients were included with a median age of 57 y (interquartile range 47, 63); 26% were women (n = 4222) and 28% (n = 4552) had a history of diabetes mellitus. The median estimated glomerular filtration rate (eGFR) was 67.5 mL/min (interquartile range 53.1, 86.7); 51.2% (n = 3068) of the recipients with eGFR < 60 received induction therapy compared to 42.5% (n = 4336) within the eGFR ≥ 60 group (P < 0.001). Adjusted multivariable analysis found that induction therapy was associated with de novo dialysis (odds ratio 1.25, 95% confidence interval 1.10-1.43, P < 0.001), with the most significant effect on patients with eGFR ≥ 60. Although significant, there was a weak correlation between center-level induction utilization and mean eGFR (r = -0.2, P < 0.001). CONCLUSION: In this analysis, the use of induction immunosuppression in orthotopic heart transplantation varied widely between centers and did not correlate strongly with pre-transplant eGFR. In addition, its utilization did not mitigate the risk of renal replacement therapy after transplantation and in fact was associated with increased risk even after adjusting for confounders most notably in patients with eGFR ≥ 60.

Nationwide variability in the use of induction immunosuppression for adult heart transplantation.

BACKGROUND: Institutional factors have been shown to impact outcomes following orthotopic heart transplantation (OHT). This study evaluated center variability in the utilization of induction therapy for OHT and its implications on clinical outcomes. METHODS: Adult OHT patients between 2010 and 2018 were identified from the United Network for Organ Sharing registry. Transplant centers were stratified based on their rates of induction therapy utilization. Mixed-effects logistic regression models were created with drug-treated rejection within 1 year as primary endpoint and individual centers as a random parameter. Risk-adjusted Cox regression was used to evaluate patient-level mortality outcomes. RESULTS: In 17,524 OHTs performed at 100 centers, induction therapy was utilized in 48.6% (n = 8411) with substantial variability between centers (interquartile range, 21.4%-79.1%). There were 36, 30, and 34 centers in the low (<29%), intermediate (29%-66%), and high (>67%) induction utilization terciles groups, respectively. Induction therapy did not account for the observed variability in the treated rejection rate at 1 year among centers after adjusting for donor and recipient factors (p = .20). No differences were observed in postoperative outcomes among induction utilization centers groups (all, p > .05). Furthermore, there was a weak correlation between the percentage of induction therapy utilization at the center-level and recipients found to have moderate (r = .03) or high (r = .04) baseline risks for acute rejection at 1 year. CONCLUSIONS: This analysis demonstrates that there is substantial variability in the use of induction therapy among OHT centers. In addition, there was a minimal correlation with baseline recipient risk or 1-year rejection rates, suggesting a need for better-standardized practices for induction therapy use in OHT.

Real-world outcomes treating patients with advanced cutaneous squamous cell carcinoma with immune checkpoint inhibitors (CPI).

BACKGROUND: Immunotherapy has revolutionised the treatment of advanced cutaneous squamous cell carcinoma (cSCC). It is important to understand both safety and efficacy in a real-world and trial-ineligible cSCC population. We aimed to evaluate safety, efficacy and molecular insights among a broader cSCC population, including immunosuppressed patients, treated with immune checkpoint inhibitors (CPI). METHODS: We present a cohort of advanced cSCC patients (n = 61) treated from 2015 to 2020 evaluating the best overall response (BOR) (RECISTv1.1) to CPI therapy, immune-related adverse events (irAEs) and tumour mutational burden (TMB) to correlate with outcomes. A validated geriatric scoring index (CIRS-G) was utilised to assess comorbidities among patients ≥75. These data were compared with published clinical trial results among the broader cSCC population. RESULTS: BOR to CPI was lower among the entire cohort when compared with trial data (31.5 vs. 48%, P < 0.01), with higher rates of progression (59 vs. 16.5%, P < 0.01), regardless of immunosuppression history or age. Grade 3+ irAEs were more common among responders (P = 0.02), while pre-treatment lymphocyte count and TMB predicted response (P = 0.02). CONCLUSIONS: We demonstrate comparatively lower response rates to CPI among real-world cSCC patients not explained by older age or immunosuppression history alone. Immune-related toxicity, absolute lymphocyte count and TMB predicted CPI response.

COVID-19 and the role of chronic inflammation in patients with obesity.

Coronavirus disease 2019 (COVID-19) and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a particular risk to people living with preexisting conditions that impair immune response or amplify pro-inflammatory response. Low-grade chronic systemic inflammation, common in people with obesity, is associated with the development of atherosclerosis, type 2 diabetes, and hypertension, well known comorbidities that adversely affect the outcomes of patients with COVID-19. Risk stratification based on the Edmonton Obesity Staging System (EOSS), which classifies obesity based on the presence of medical, mental, and/or functional complications rather than on body mass index (BMI), has been shown to be a better predictor of all-cause mortality and it may well be that EOSS stages may better describe the risk of hyperinflammation in patients with COVID-19 infection. Analyzing a group of metabolic ill patients with obesity (EOSS 2 and 3), we found an increased interleukin-6 and linear regression analysis showed a positive correlation with C-reactive protein (CRP) (p = 0.014) and waist-to-hip-ratio (WHR) (p = 0.031). Physicians should be aware of these findings in patients with COVID-19 infection. Early identification of possible hyperinflammation could be fundamental and should guide decision making regarding hospitalization, early respiratory support, and therapy with immunosuppression to improve mortality.

The Effect of Immunosuppression on Emergency Colectomy Outcomes: A Nationwide Retrospective Analysis.

BACKGROUND: The impact of immunosuppression on the outcomes of emergent surgery remains poorly described. We aimed to quantify the impact of chronic immunosuppression on outcomes of patients undergoing emergent colectomy (EC). METHODS: The Colectomy-Targeted ACS-NSQIP database 2012-2016 was queried for patients who underwent colectomy for an emergent indication. As per NSQIP, chronic immunosuppression was defined as the use of corticosteroid or immunosuppressant medication within the prior 30 days. Patients undergoing EC for any indication were divided into two groups: immunosuppressant use (IMS) and no immunosuppressant use (NIS). Patients were propensity-score-matched on demographics, comorbidities, preoperative laboratory values, and operative variables in a 1:1 ratio to control for confounding factors. The primary outcome was 30-day mortality. Secondary outcomes included overall 30-day morbidity, individual postoperative complications (e.g., wound dehiscence, anastomotic leak, and sepsis), and hospital length of stay. RESULTS: Out of a total of 130,963 patients, 17,707 patients underwent an EC, of which 15,422 were NIS and 2285 were IMS. Totally, 2882 patients were matched (1441 NIS; 1441 IMS). The median age was 66 [IQR 56-76]; 56.8% were female; patients more frequently underwent a diversion procedure rather than primary anastomosis (68.4% vs 31.6%). Overall, as compared to NIS, IMS patients had higher 30-day mortality (21.4% vs 18.5%, p = 0.045) and overall morbidity (79.7% vs 75.7%, p = 0.011). Particularly, IMS patients had increased rates of unplanned intubations (11.5% vs 7.9%, p = 0.001), wound dehiscence (5.7% vs 3.5%, p = 0.006), progressive renal insufficiency 2.2% vs 1.2%, p = 0.042), pneumonia (12.6% vs 10.0%, p = 0.029), and longer median hospital length of stay [12.0 (8.0-21.0) vs 11.0 (7.0-19.0), p < 0.001] as compared to NIS patients. CONCLUSIONS: Chronic immunosuppression is independently associated with a significant and quantifiable increase in 30-day mortality and complications for patients undergoing EC. Our results provide the emergency surgeon with quantifiable risk estimates that can help guide better patient counseling while setting reasonable expectations.

Immunosuppression and Graft Rejection in Living-related HLA-identical Renal Transplantation: The RADOVFULL Study.

BACKGROUND: We aimed to describe the immunosuppressive regimens and graft rejection rates in living-related HLA-identical (LR HLAid) renal transplantation. METHODS: We performed a retrospective multicenter analysis of the French national database for LR HLAid renal transplantations performed between 2002 and 2012. Univariate and multivariate analysis were performed to determine risk factors for graft rejection in LR HLAid recipients. RESULTS: A total of 27 218 renal transplantations were performed, of whom 163 had a LR HLAid donor. About immunosuppressive treatment, <60% of the cohort had induction therapy with polyclonal or monoclonal antibodies, 28% did not receive calcineurin inhibitors, and 36% did not receive steroids in maintenance. Biopsy-proven acute rejection was diagnosed in 21 patients (12.9%). Rejection occurred on an average of 24 months after transplantation, in 28.5% of the cases after minimization of immunosuppression. Factors associated with rejection were age of recipient (OR, 0.91 [0.84-0.96]; P = 0.003), the body mass index of donors (odds ratio [OR], 1.22 [1.04-1.46]; P = 0.01), and minimization of immunosuppression (OR, 26.2 [5.48-166.6]; P < 0.001). Overall and graft survival rates were not statistically different according to rejection at 1, 5, and 10 years posttransplantation. CONCLUSIONS: Minimization of immunosuppression should be done with caution in LR HLAid renal transplantations.

Comparison of frontline treatment with intensive immunosuppression therapy and HLA-haploidentical hematopoietic stem cell transplantation for young patients with severe aplastic anemia - A meta analysis.

AIM: To compare the survivals and treatment related complications between immunosuppression therapy (IST) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) on children and young adults with severe aplastic anemia (SAA) in East Asia during the last 10 years. METHODS: After looking through Pubmed, Embase, Web of Science and Wanfang Data, a total of 491 patients from 7 retrospective studies conducted in East-Asia were included for meta-analysis based on Stata program. Publication bias was measured by Begger and Egger tests. 1/3/5/10 years overall survivals (OS), failure free survivals (FFS), incidence rates of adverse events and their 95% confidence intervals (CI) were pooled and compared. RESULTS: There was no difference of 1/3/5/10 years OS between IST group and haplo-HSCT group, but the 1/3/5/10 years FFS were significantly better in haplo-HSCT group compared with IST group (p < 0.01). However, higher incidence of infections was observed in haplo-HSCT group compared with IST group (76% versus 45%, p < 0.001). The pooled estimates for acute graft versus host disease (aGVHD) and chronic graft versus host disease (cGVHD) were 54% (95% Cl, 43%～64%) and 43% (95% CI, 18%～68%), respectively for haplo-HSCT group. Among them 38% (95%CI, 22%～54%) was grade III aGVHD and 11% (95% Cl, 0%～22%) was grade III-IV aGVHD. Death causes included severe infection, bleeding in IST group and infection, GVHD in haplo-HSCT group. CONCLUSIONS: The long-term survivals were similar for young patients with SAA who received IST or haplo-HSCT as the frontline treatment. The haplo-HSCT group showed a better FFS, on the other hand, had higher incidence of infection and GVHD.

Immunosuppression reduction in kidney transplant recipients during bacterial infection-A retrospective study.

BACKGROUND: Immunosuppression reduction is a common practice in the management of bacterial infection among kidney transplant recipients (KTRs). This practice, however, is based on limited evidence. METHODS: Retrospective study comparing clinical outcomes of KTRs whose antimetabolite was discontinued vs continued during hospitalization due to bacterial infection, considering calcineurin inhibitors (CNI) levels. Primary outcome was a composite of clinical failure at day 5; all-cause mortality; and/or re-hospitalization at 90 days. Multivariable analysis of risk factors for the primary outcome was performed using a propensity-matched cohort. RESULTS: We included 183 KTRs hospitalized with bacterial infection. Neither discontinuation of antimetabolites nor lower levels of CNI at infection onset were associated with a significant decrease the composite primary outcome. No significant difference in graft loss or rejection was demonstrated between patients with low vs high CNI levels or discontinuation vs continuation of antimetabolite. In multivariable analysis, CNI levels and management of antimetabolite were not significantly associated with adverse outcome. CONCLUSIONS: Immunosuppression reduction in hospitalized KTRs with bacterial infection did not offer a clinical advantage in terms of mortality, re-hospitalization, or clinical success. An interventional study evaluating continuation of immunosuppression vs reduction should be considered.

Epidemiologic perspectives on immunosuppressed populations and the immunosurveillance and immunocontainment of cancer.

The advent in the last several years of effective immunotherapy for cancer has renewed interest in the role of the immune system in controlling cancer. The idea that the immune system can help control cancer has a long history. Solid organ transplant recipients (SOTRs) as well as human immunodeficiency virus (HIV)-infected people are affected by cell-mediated immune dysfunction. Epidemiologic studies of these populations reveal a pattern characterized by a strongly increased incidence of virus-related cancers (eg, Kaposi sarcoma, non-Hodgkin lymphoma, and anogenital cancers). In addition, recent epidemiologic studies have evaluated cancer-specific mortality among SOTRs and HIV-infected people following a cancer diagnosis. For a wider range of cancers-not limited to those caused by viruses, and including melanoma and cancers of the colorectum, lung, and breast- these immunosuppressed cancer patients have higher cancer-specific mortality than other cancer patients. This latter group of cancers somewhat mirrors those for which immunotherapy with checkpoint inhibitors is approved. These epidemiologic observations suggest that there are 2 distinct immune selection processes in humans: immunosurveillance directed against premalignant cells before cancer diagnosis (most relevant for preventing virus-related cancers), and "immunocontainment" directed against established cancers. These processes thus appear relevant for different groups of malignancies and may have different mechanisms.

Management of skin cancer in recipients of solid organ transplants.

Recent improvements in post-transplant care have led to an increased life expectancy for recipients of organ transplants. These patients require lifelong immunosuppression, which is associated with an increased incidence of malignant disease. Skin cancers are the most common malignancies seen in recipients of organ transplants and are associated with significant morbidity and mortality. This review describes factors pertaining to the development and prognosis of skin cancers in recipients of organ transplants, as well as outlining prevention and management strategies in this cohort.

l-arginine minimizes immunosuppression and prothrombin time and enhances the genotoxicity of 5-fluorouracil in rats.

OBJECTIVE: The aim of this study was to evaluate the effect of low doses of l-arginine supplementation on hemogram, integrity of DNA and spleen, inflammatory infiltrate in the jejunum, and in the coagulogram of rats submitted to 5-fluorouracil (5-FU) chemotherapy. METHODS: Thirty-two Wistar rats were fed commercial feed and water ad libitum and grouped into four (eight rats per group): The control group was given a 0.9% physiologic solution to simulate the application of 5-FU in the other groups; the G5-FU group was given a dose of 5-FU; the GArg50 and GArg100 groups were given a dose of 5-FU and supplemented with 50 and 100 mg l-arginine/d added in the drinking water ad libitum. RESULTS: The rats in the GArg50 group did not lose weight after chemotherapy. GArg50 rats presented polycythemia owing to dehydration caused by diarrhea generated by 5-FU. GArg100 rats had increased total leukocyte count, eosinophils, lymphocytes, and index in the total index of DNA damage, yet showed a reduction in prothrombin time and in the spleen depletion index. Rats in the G5-FU, GArg50, and GArg100 groups had similar moderate inflammatory infiltrate in the jejunum. CONCLUSION: Supplementation with 100 mg/d of l-arginine minimized immunosuppression, spleen depletion, and prothrombin time and contributed to the breakdown of 5-FU-generated DNA in Wistar rats. Supplementation with 50 mg/d of l-arginine decreased the weight loss generated by 5-FU in Wistar rats. Supplements with 50 or 100 mg of l-arginine did not interfere with 5-FU-generated jejunal inflammatory infiltrate.

Risk of Parkinson disease in Sjögren syndrome administered ineffective immunosuppressant therapies: A nationwide population-based study.

To determine the incidence and risk of Parkinson disease (PD) in patients with Sjögren syndrome (SS) according to a nationwide population-based database.In total, 12,640 patients in the SS cohort and 50,560 in the non-SS cohort were enrolled from Taiwan's National Health Insurance Research Database from 2000 to 2010. We used the Cox multivariable proportional hazards model to determine the risk factors for PD in the SS cohort.We observed an increased incidence of PD in patients with SS, with a crude hazard ratio (HR) of 1.40 and an adjusted HR (aHR) of 1.23. The cumulative incidence of PD was 1.95% higher in the SS cohort than in the non-SS cohort. The SS cohort had an elevated HR under medication use, namely cevimeline and pilocarpine (crude HR, 1.28), hydroxychloroquine (crude HR, 1.43; aHR, 1.46), and methylprednisolone (crude HR, 2.21; aHR, 1.49). Patients receiving other non-hydroxychloroquine immunosuppressant therapies had a lower risk (aHR, 0.86) of PD. Furthermore, patients with SS aged 20 to 49 years had a 1.93-fold higher risk of PD than did those without SS (aHR, 1.93). The risk of PD was higher (aHR, 2.20) in patients with SS without comorbidities than in those with comorbidities. The aHR of PD significantly increased when the follow-up period exceeded 9 years (aHR, 1.93).We determined an increased risk of PD in patients with SS. Further investigation is warranted to determine the possible underlying mechanisms and the potential role of non-hydroxychloroquine immunosuppressants in ameliorating PD.