PERANG SALIB III (Faktor Penyebab, Peran dan Perjuangan Shalahuddin Al Ayyubi)

M. Iqbal Hasby A. 1411315000. PERANG SALIB III (FAKTOR PENYEBAB, PERAN DAN PERJUANGAN SHALAHUDDIN AL AYYUBI). Skripsi. Jurusan Sejarah Kebudayaan Islam. Fakultas Adab Dakwah. IAIN Syekh Nurjati Cirebon. 2016. Perang Salib merupakan sebuah peristiwa peperangan yang terjadi dalam kurun waktu kurang lebih dua ratus tahun (1096-1292 M), yang mempertemukan Umat Islam dan Kristen Eropa demi mendapatkan kekuasaan atas wilayah Baitul Maqdis (Yerusalem). Dalam serangkaian Perang Salib ini telah memunculkan peran seorang tokoh yang cukup berjasa besar peranannya dalam mempertahankan Baitul Maqdis (Yerusalem), dia adalah seorang raja dan pahlawan umat Islam yaitu Shalahuddin Al Ayyubi. Sesuai dengan latar belakang yang telah di ungkapkan di atas, di sini penulis mencoba menguraikan rumusan masalah mengenai latar belakang perang salib dan sejauh mana peran dan perjuangan Shalahuddin Al Ayyubi dalam peristiwa Perang Salib, yang dirumuskan ke dalam pembahasan terkait latar belakang terjadinya perang salib serta peran dan perjuangan yang dimunculkan oleh Shalahuddin Al Ayyubi dalam peristiwa Perang Salib tersebut. Peristiwa ini memfokuskan pembahasannya pada peran penting seorang Shalahuddin dalam mempertahankan Baitul Maqdis (Yerusalem) saat Perang Salib III (1096 s/d 1198 M) sehingga tetap di dalam kekuasaan Umat Muslim. Untuk metode penelitian ini penulis menggunakan pendekatan Library Research dengan menggunakan metode heuristik, di mana setelah sumber-sumber informasi terkait diperoleh, berikutnya dilakukan kritik dan verivikasi kemudian dibuat alur yang logis dengan penafsiran-penafsiran agar apa yang penulis tulis memiliki alur cerita sejarah yang runtut dengan metode historiografi. Dari hasil penelitian tersebut dapat ditarik sebuah kesimpulan bahwa Perang Salib terjadi kurang lebih selama 200 tahun yang memperebutkan wilayah (Baitul Maqdis/Yerusalem) yang diangap suci oleh 3 agama besar (Yahudi, Kristen dan Islam) karena faktor Agama, faktor Politik (Kekuasaan), dan faktor Ekonomi. Shalahuddin Al Ayyubi menjadi tokoh yang paling dikenal dalam peristiwa Perang Salib ini, peran dan perjuangannya yang cukup berarti demi mempertahankan Baitul Maqdis (Yerusalem) dari serangan Pasukan Salib Eropa. Kata Kunci : Perang Salib, Shalahuddin Al Ayyubi, Peran dan perjuanga

Mycophenolate pharmacokinetics and pharmacodynamics in belatacept treated renal allograft recipients – a pilot study

<p>Abstract</p> <p>Background</p> <p>Mycophenolic acid (MPA) is widely used as part of immunosuppressive regimens following allograft transplantation. The large pharmacokinetic (PK) and pharmacodynamic (PD) variability and narrow therapeutic range of MPA provide a potential for therapeutic drug monitoring. The objective of this pilot study was to investigate the MPA PK and PD relation in combination with belatacept (2^ndgeneration CTLA4-Ig) or cyclosporine (CsA).</p> <p>Methods</p> <p>Seven renal allograft recipients were randomized to either belatacept (n = 4) or cyclosporine (n = 3) based immunosuppression. Samples for MPA PK and PD evaluations were collected predose and at 1, 2 and 13 weeks posttransplant. Plasma concentrations of MPA were determined by HPLC-UV. Activity of inosine monophosphate dehydrogenase (IMPDH) and the expressions of two <it>IMPDH </it>isoforms were measured in CD4+ cells by HPLC-UV and real-time reverse-transcription PCR, respectively. Subsets of T cells were characterized by flow cytometry.</p> <p>Results</p> <p>The MPA exposure tended to be higher among belatacept patients than in CsA patients at week 1 (P = 0.057). Further, MPA concentrations (AUC_{0–9 h}and C₀) increased with time in both groups and were higher at week 13 than at week 2 (P = 0.031, n = 6). In contrast to the postdose reductions of IMPDH activity observed early posttransplant, IMPDH activity within both treatment groups was elevated throughout the dosing interval at week 13. Transient postdose increments were also observed for <it>IMPDH1 </it>expression, starting at week 1. Higher MPA exposure was associated with larger elevations of <it>IMPDH1 </it>(r = 0.81, P = 0.023, n = 7 for MPA and <it>IMPDH1 </it>AUC_{0–9 h}at week 1). The maximum <it>IMPDH1 </it>expression was 52 (13–177)% higher at week 13 compared to week 1 (P = 0.031, n = 6). One patient showed lower MPA exposure with time and did neither display elevations of IMPDH activity nor <it>IMPDH1 </it>expression. No difference was observed in T cell subsets between treatment groups.</p> <p>Conclusion</p> <p>The significant influence of MPA on <it>IMPDH1 </it>expression, possibly mediated through reduced guanine nucleotide levels, could explain the elevations of IMPDH activity within dosing intervals at week 13. The present regulation of IMPDH in CD4+ cells should be considered when interpreting measurements of IMPDH inhibition.</p

Hypomagnesemia, insulin secretion and action in patients without diabetes, 1 year after kidney transplantation

Introduction: Hypomagnesemia after kidney transplantation has been reported as a potential risk factor for development of post-transplant diabetes mellitus. Methods: In kidney transplant recipients undergoing an oral glucose tolerance test during one-year surveillance follow-up we estimated insulin sensitivity with the Matsuda index, a modified Stumvoll index, and HOMA-2 IR. First and second phase insulin secretion was assessed using the Stumvoll equation. Participants were categorized into tertiles by plasma magnesium levels, (&lt;0.7, 07–0.78,&gt;0.78 mmol/L). Results: We included 208 patients (62% men, median age 51 years). Patients in the lowest compared to the highest magnesium tertile had higher measured GFR (mean 59 vs. 49 mL/min, p = 0.002), tacrolimus trough concentration (mean 6.7 vs. 5.5 μg/L, p &lt; 0.001), and fasting plasma glucose (mean 5.5 vs. 5.3 mmol/L, p = 0.03). There was no significant difference in the Matsuda index between magnesium tertiles, nor in insulin sensitivity assessed by modified Stumvoll index, HOMA-2 IR, first or second phase insulin. Results indicate a non-significant trend toward lower disposition index in the lowest vs. highest tertile (p = 0.052). Conclusion: In kidney transplant recipients with lower compared to normal plasma magnesium levels we found a higher fasting plasma glucose but no differences in insulin sensitivity indexes nor dynamic insulin measurements.</p

Increased long-term risk for hypertension in kidney donors – a retrospective cohort study

Kidney donors may be at increased risk of end-stage renal disease and premature mortality. Elevated blood pressure after donation may contribute to the increased risks. In this cohort study, we have assessed long-term risk for the development of hypertension in kidney donors compared to a control group potentially eligible as donors. Follow-up data were obtained from previous living kidney donors. A healthy control group with baseline assessment from similar time periods as the donor nephrectomies was selected. Hypertension was defined as blood pressure >140/90, use of blood pressure medication, or established diagnosis of hypertension. Stratified logistic regression was used to estimate risk of hypertension at follow-up, adjusted for systolic blood pressure at baseline, age at follow-up, time since donation/baseline, gender, smoking at baseline, and BMI at baseline. A total of 368 donors (36%) had hypertension at follow-up, and 241 of these (23%) were using blood pressure medication. In adjusted stratified logistic regression analyses, odds ratio for hypertension was significantly increased (1.25, 95% confidence interval 1.12–1.39, P < 0.001) in donors compared with controls. Kidney donors appear to be at increased long-term risk for hypertension compared with healthy controls. This finding supports regular follow-up of blood pressure in kidney donors.acceptedVersio

Clinical triage of patients on kidney replacement therapy presenting with COVID-19:an ERACODA registry analysis

Background. Patients on kidney replacement therapy (KRT) are at very high risk of coronavirus disease 2019 (COVID-19). The triage pathway for KRT patients presenting to hospitals with varying severity of COVID-19 illness remains ill-defined. We studied the clinical characteristics of patients at initial and subsequent hospital presentations and the impact on patient outcomes.Methods. The European Renal Association COVID-19 Database (ERACODA) was analysed for clinical and laboratory features of 1423 KRT patients with COVID-19 either hospitalized or nonhospitalized at initial triage and those re-presenting a second time. Predictors of outcomes (hospitalization, 28-day mortality) were then determined for all those not hospitalized at initial triage.Results. Among 1423 KRT patients with COVID-19 [haemodialysis (HD), n = 1017; transplant, n = 406), 25% (n = 355) were not hospitalized at first presentation due to mild illness (30% HD, 13% transplant). Of the non-hospitalized patients, only 10% (n = 36) re-presented a second time, with a 5-day median interval between the two presentations (interquartile range 2-7 days). Patients who re-presented had worsening respiratory symptoms, a decrease in oxygen saturation (97% versus 90%) and an increase in C-reactive protein (26 versus 73 mg/L) and were older (72 vs 63 years) compared with those who did not return a second time. The 28-day mortality between early admission (at first presentation) and deferred admission (at second presentation) was not significantly different (29% versus 25%; P = 0.6). Older age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation were identified as risk predictors of mortality when representing after discharge at initial triage.Conclusions. This study provides evidence that KRT patients with COVID-19 and mild illness can be managed effectively with supported outpatient care and with vigilance of respiratory symptoms, especially in those with risk factors for poor outcomes. Our findings support a risk-stratified clinical approach to admissions and discharges of KRT patients presenting with COVID-19 to aid clinical triage and optimize resource utilization during the ongoing pandemic

Low Immunization Rate in Kidney Transplant Recipients Also After Dose 2 of the BNT162b2 Vaccine: Continue to Keep Your Guard up!

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Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients

Following a successful renal transplantation circulating markers of inflammation may remain elevated, and systemic inflammation is associated with worse clinical outcome in renal transplant recipients (RTRs). Vitamin D-receptor (VDR) activation is postulated to modulate inflammation and endothelial function. We aimed to explore if a synthetic vitamin D, paricalcitol, could influence systemic inflammation and immune activation in RTRs. Newly transplanted RTRs were included in an open-label randomized controlled trial on the effect of paricalcitol on top of standard care over the first post-transplant year. Fourteen pre-defined circulating biomarkers reflecting leukocyte activation, endothelial activation, fibrosis and general inflammatory burden were analyzed in 74 RTRs at 8 weeks (baseline) and 1 year post-engraftment. Mean changes in plasma biomarker concentrations were compared by t-test. The expression of genes coding for the same biomarkers were investigated in 1-year surveillance graft biopsies (n = 60). In patients treated with paricalcitol circulating osteoprotegerin levels increased by 0.19 ng/ml, compared with a 0.05 ng/ml increase in controls (p = 0.030). In graft tissue, a 21% higher median gene expression level of TNFRSF11B coding for osteoprotegerin was found in paricalcitol-treated patients compared with controls (p = 0.026). Paricalcitol treatment did not significantly affect the blood- or tissue levels of any other investigated inflammatory marker. In RTRs, paricalcitol treatment might increase both circulating and tissue levels of osteoprotegerin, a modulator of calcification, but potential anti-inflammatory treatment effects in RTRs are likely very modest

Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management

Background. Following kidney transplantation (KT), cytomegalovirus (CMV) infection remains an important challenge. Both prophylactic and preemptive antiviral protocols are used for CMV high-risk kidney recipients (donor seropositive/recipient seronegative; D+/R–). We performed a nationwide comparison of the 2 strategies in de novo D+/R– KT recipients accessing long-term outcomes. Methods. A nationwide retrospective study was conducted from 2007 to 2018, with follow-up until February 1, 2022. All adult D+/R– and R+ KT recipients were included. During the first 4 y, D+/R– recipients were managed preemptively, changing to 6 mo of valganciclovir prophylaxis from 2011. To adjust for the 2 time eras, de novo intermediate-risk (R+) recipients, who received preemptive CMV therapy throughout the study period, served as longitudinal controls for possible confounders. Results. A total of 2198 KT recipients (D+/R–, n = 428; R+, n = 1770) were included with a median follow-up of 9.4 (range, 3.1–15.1) y. As expected, a greater proportion experienced a CMV infection in the preemptive era compared with the prophylactic era and with a shorter time from KT to CMV infection (P < 0.001). However, there were no differences in long-term outcomes such as patient death (47/146 [32%] versus 57/282 [20%]; P = 0.3), graft loss (64/146 [44%] versus 71/282 [25%]; P = 0.5), or death censored graft loss (26/146 [18%] versus 26/282 [9%]; P = 0.9) in the preemptive versus prophylactic era. Long-term outcomes in R+ recipients showed no signs of sequential era–related bias. Conclusions. There were no significant differences in relevant long-term outcomes between preemptive and prophylactic CMV-preventive strategies in D+/R– kidney transplant recipients.publishedVersio

Case Report: Donor-derived herpes simplex virus type 1 hepatitis in a kidney transplant recipient with fatal outcome

Current screening practices have significantly reduced the transmission of donor-derived infections through organ transplantations. However, in exceptional cases, a deceased donor may harbor an undetected active infection, or abnormal blood test results may be mistakenly attributed to the dying process, resulting in missed infections. These ongoing infections can then be transmitted through the grafts. This report presents a case of confirmed donor-derived herpes simplex virus type 1 (HSV-1) hepatitis following kidney transplantation. The HSV-1 infection in the recipient was initially overlooked and misattributed to a probable mycophenolate mofetil-induced etiology, which led to a delay in initiating antiviral therapy. The recipient subsequently developed HSV-1 hepatitis, which progressed to liver failure and multiorgan failure, ultimately resulting in death. As a result of this case, our transplant center promptly revised its screening and prophylactic antiviral treatment protocols. All kidney transplant recipients who are herpes simplex virus (HSV) antibody-negative now receive valaciclovir until the donor's HSV DNA PCR status is confirmed to be negative