Late acute cellular rejection after switch to everolimus monotherapy at 11 months following liver transplantation

Background Acute cellular rejection beyond the 6th month posttransplant is an uncommon complication after liver transplantation. The inadequate immunosuppression (IS) remains the main risk factor. We report a case of acute cellular rejection after a switch to everolimus monotherapy at 11 months following liver transplantation. Case presentation This was a 69-year-old man who underwent liver transplantation after hepatocellular carcinoma. The initial immunosuppression was a combination of three immunosuppressive drugs (corticosteroids + tacrolimus + mycophenolate mofetil). The corticosteroid therapy was stopped at the 4th month posttransplant. Serious side effects of the immunosuppressive drugs (agranulocytosis and renal dysfunction), which occurred 4 months after transplantation, required a reduction and then a discontinuation of tacrolimus and mycophenolate mofetil. Everolimus was introduced as a replacement. The patient was consulted at 11 months after liver transplantation, 1 month after stopping the two immunosuppressive drugs, for liver function test abnormalities such as cytolysis and anicteric cholestasis. A moderate late acute cellular rejection was confirmed by a liver biopsy. A satisfactory biological evolution was observed following corticosteroid boluses and optimization of basic immunosuppressive drugs. Conclusion Late acute cellular rejection remains an uncommon complication, observed mostly in the first year after liver transplantation. The main risk factor is usually the decrease of immunosuppression.

Chronic glucocorticoids consumption triggers and worsens experimental Alzheimer’s disease-like pathology by detrimental immune-modulations

Introduction: Among the risk factors identified in the sporadic forms of Alzheimer’s disease (AD), environmental and lifestyle elements are of growing interest. Clinical observations suggest that stressful events can anticipate AD onset, while stress-related disorders can promote AD. Here, we tested the hypothesis that a chronic treatment with glucocorticoids, is sufficient to trigger or exacerbate AD molecular hallmarks. Methods: We first validated a rat model of experimental chronic glucocorticoids consumption (corticosterone in drinking water for 4 weeks). Then, to evaluate the consequences of chronic glucocorticoids consumption on the onset of amyloid-β (Aβ) toxicity, animals chronically treated with glucocorticoids were intracerebroventricularly injected with an oligomeric solution of Aβ25-35 (oAβ) (acute model of AD). We evaluated AD-related cognitive deficits and pathogenic mechanisms, with a special emphasis on neuroinflammatory markers. Results: Chronic corticosterone consumption caused the inhibition of the non-amyloidogenic pathways, the impairment of Aβ clearance processes and the induction of amyloidogenic pathways in the hippocampus. The principal enzymes involved in glucocorticoid receptor (GR) activation and Tau phosphorylation were upregulated. Importantly, the AD-like phenotype triggered by chronic corticosterone was analogous to the one caused by oAβ. These molecular commonalities across models were independent from inflammation, as chronic corticosterone was immunosuppressive while oAβ was pro-inflammatory. When chronic corticosterone consumption anticipated the induction of the oAβ pathology, we found a potentiation of neuroinflammatory processes associated with an exacerbation of synaptic and memory deficits but also an aggravation of AD-related hallmarks. Discussion/Conclusion: This study unravels new functional outcomes identifying chronic corticosterone consumption as a main risk factor for AD and suggests that glucocorticoid-based therapies should be prescribed with caution in populations with AD risk.

Dampak Trichinella sp. dalam Daging Babi Terhadap Kesehatan Masyarakat

Trichinellosis/Trichinosis is one of the most common zoonotic parasites in the world caused by infection with Trichinella nematodes. The infection occurs after the larvae have been eaten in the muscles of the infected animal. Due to its spread and spread, several outbreaks of trichinosis have occurred around the world, which has caused serious public health problems. The main risk factor for trichinosis is the consumption of raw or undercooked meat from pigs and hunted meat. In the first stage of infection, adults nematode in the intestine can cause transient gastroenteritis, but the most serious symptoms are associated with the larval formation and muscle migration. a study conducted in India to investigate at the clinical and biochemical profile of Trichinella infection stated that clinical symptoms first appeared at 2-3 weeks after consuming pork and the symptoms would gradually disappear at 4-5 weeks, but there were also some who experienced myalgia. Supervision and implementing proper biosecurity in livestock areas by monitoring and surveillance of the risk of Trichinella infection in pig products and their derivatives as well as preventing transmission to humans.

Antibody and Protein Profiles in Glaucoma: Screening of Biomarkers and Identification of Signaling Pathways

Glaucoma represents a group of chronic neurodegenerative diseases, constituting the second leading cause of blindness worldwide. To date, chronically elevated intraocular pressure has been identified as the main risk factor and the only treatable symptom. However, there is increasing evidence in the recent literature that IOP-independent molecular mechanisms also play an important role in the progression of the disease. In recent years, it has become increasingly clear that glaucoma has an autoimmune component. The main focus nowadays is elucidating glaucoma pathogenesis, finding early diagnostic options and new therapeutic approaches. This review article summarizes the impact of different antibodies and proteins associated with glaucoma that can be detected for example by microarray and mass spectrometric analyzes, which (i) provide information about expression profiles and associated molecular signaling pathways, (ii) can possibly be used as a diagnostic tool in future and, (iii) can identify possible targets for therapeutic approaches.

COVID-19 Infection in Patients with Glomerular Disease: Follow-up Results from the IRoc-GN International Registry

Background: The acute and long-term effects of SARS-CoV2 infection in individuals with glomerular diseases (GN) are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in glomerulonephritis (IRoc-GN). Methods: We collected serial information on kidney-related and kidney-unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with COVID-19 and a median follow-up period of 6.4 (IQR: 2.3 to 9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple-regression models were adjusted for age, gender, ethnicity, and RAASi use. Results: After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio [aOR] for AKI: 1.28 [95% CI: 0.46 to 3.60]; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (aOR per 1SD unit decrease in eGFR: 3.04 [95% CI: 1.76 to 5.28]; P<0.001). GN patients developing AKI were less likely to recover pre-COVID-19 eGFR compared to controls (adjusted 6-month post-COVID-19 eGFR = 0.41 [95%CI: 0.25 to 0.56] times pre-COVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease (FSGS/MCD) were associated with a lower post-COVID-19 eGFR. Conclusions: Pre-COVID-19 eGFR is the main risk factor for AKI regardless from GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or FSGS/MCD diagnosis) should be closely monitored not only during the acute phases of COVID-19, but also after its resolution.

Bacterial and Fungal Co-infection in a Cohort of 333 Patients Hospitalized for COVID-19 (COINFECOVID Study)

BackgroundCoinfections in COVID19 appear to worsen hospitalized patients prognosis.ObjectiveTo describe the characteristics of bacterial and fungal coinfections in patients admitted for COVID19 and to identify the risk factors associated with its occurrence.Patients and MethodsSingle-center retrospective study reviewing medical records of patients with COVID19 diagnosed with bacterial or fungal infection during hospital admission.Results333 patients were analyzed during March 15-May 15, 2020. 16.82% had some coinfection during admission. Coinfections were more frequent in patients with comorbidities (80.36% vs 19.64% p<0.025) and in those ICU admitted (52.46% vs 8.86%, p<0.001). Coinfections were significantly more frequent in patients with neutrophilia>7500 and increased procalcitonin on admission as well as lymphopenia<1500 on day 5. Mortality in patients with coinfection was 26.79% vs 23.47% in non-coinfected (p 0.596). Length of stay was longer in coinfected patients (mean 30.59 vs 13.47, p<0.01). Most frequent microorganisms were Enterococci, Candida spp, Enterobacteriaceae and Pseudomonas spp. 74% of patients received ceftriaxone: 17.34% of those treated had a coinfection compared to 15.48% not treated (p 0.694).ConclusionsOccurrence of coinfections is frequent and prolongs hospital stay without influencing mortality. The presence of comorbidities and ICU stay were identified as the main risk factor for coinfection, while increased neutrophils and procalcitonin at admission and lymphopenia during evolution were the main biological predictors. Enterococcus was the most frequent pathogen. Ceftriaxone use does not protect against appearance of bacterial infections. C. albicans was the most frequently isolated fungus and was associated with prolonged ICU stay.

Accuracy of H. pylori fecal antigen test using fecal immunochemical test (FIT)

Background Gastric and colorectal cancer (CRC) are both one of the most common cancers worldwide. In many countries fecal immunochemical tests (FIT)-based CRC screening has been implemented. We investigated if FIT can also be applied for detection of H. pylori, the main risk factor for gastric cancer. Methods This prospective study included participants over 18 years of age referred for urea breath test (UBT). Patients were excluded if they had used antibiotics/bismuth in the past 4 weeks, or a proton pomp inhibitor (PPI) in the past 2 weeks. Participants underwent UBT, ELISA stool antigen test in standard feces tube (SAT), ELISA stool antigen test in FIT tube (Hp-FIT), and blood sampling, and completed a questionnaire on user friendliness. UBT results were used as reference. Results A total of 182 patients were included (37.4% male, median age 52.4 years (IQR 22.4)). Of these, 60 (33.0%) tested H. pylori positive. SAT and Hp-FIT showed comparable overall accuracy 71.1% (95%CI 63.2–78.3) vs. 77.6% (95%CI 70.4–83.8), respectively (p = 0.97). Sensitivity of SAT was 91.8% (95%CI 80.4–97.7) versus 94.2% (95%CI 84.1–98.9) of Hp-FIT (p = 0.98). Serology scored low with an overall accuracy of 49.7% (95%CI 41.7–57.7). Hp-FIT showed the highest overall user convenience. Conclusions FIT can be used with high accuracy and sensitivity for diagnosis of H. pylori and is rated as the most convenient test. Non-invasive Hp-FIT test is highly promising for combined upper and lower gastrointestinal (pre-) cancerous screening. Further research should investigate the clinical implications, benefits and cost-effectiveness of such an approach.

Necroptosis inhibition counteracts axonal degeneration, cognitive decline and key hallmarks of aging, promoting brain rejuvenation.

Age is the main risk factor for cognitive impairment and the development of neurodegenerative diseases. In the aged brain, axonal degeneration is an early pathological event, preceding neuronal dysfunction and brain disabilities in humans, primates, rodents, and invertebrates. Necroptosis activation mediates degeneration of mechanical and chemically injured axons, but whether this pathway triggers axonal degeneration and cognitive impairment during brain aging has not been studied. Here we show that necroptosis is activated in the hippocampus during aging, especially in axonal tracts. Loss of the main necroptotic effector, Mlkl, was sufficient to delay age-associated axonal degeneration. Accordingly, aged Mlkl-KO mice also displayed a youthful phenotype at the synaptic and functional level, protecting against decreased synaptic transmission and memory decline. Short-term pharmacologic inhibition of necroptosis by targeting RIPK3 in aged mice, proved to be extraordinarily effective at reverting axonal degeneration and hippocampal-dependent functional impairment at the electrophysiological and behavioral level. Remarkably, a comprehensive quantitative proteomic analysis uncovered a set of aging hallmarks that were recovered in both, the genetic and pharmacologic models of necroptosis inhibition, including molecular biofunctions associated with brain rejuvenation. Taken together, these findings demonstrate that necroptosis contributes to the age-associated deterioration of axonal integrity, affecting hippocampal neuronal connectivity and cognitive function in aged individuals. We therefore propose necroptosis as an attractive target for the future development of geroprotective tools to treat age-related disabilities.

Micronodular basal cell carcinoma of the scrotum: a case report and review of the literature

Introduction Basal cell carcinoma is the most common nonmelanotic skin cancer. It has variable clinical and histological subtypes that vary in their aggressiveness and liability to recurrence and metastasis. Chronic ultraviolet radiation exposure is considered to be the main risk factor for developing basal cell carcinoma; therefore, it typically arises on sun-exposed skin, mainly the head and neck. Case presentation We present the case of a 55-year-old Caucasian male who presented with a lesion on the scrotum for 2 years. The lesion was clinically presumed benign and initially treated with curettage. Microscopic examination revealed an incompletely resected micronodular basal cell carcinoma with sebaceous differentiation. Therefore, a second excisional biopsy was performed to completely excise the incidentally discovered malignant tumor. Conclusion We report the first case of micronodular basal cell carcinoma arising on the scrotum. The goal of our article is to draw clinicians’ attention to the possible involvement of unexposed skin with basal cell carcinoma, and we highlight the importance of accurate diagnosis and prompt treatment due to the aggressive nature of micronodular basal cell carcinoma.