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Intrathecal morphine is a very good analgesic agent and was used frequently in the past. Its use has decreased over the years due to side effects such as respiratory depression, nausea, vomiting, pruritis, and so on. Also, with the introduction of drugs like clonidine and the availability of ultrasonography for regional blocks, the role of morphine has declined. Yet, there are surgeries where intrathecal morphine supersedes all other analgesic modalities to provide excellent intraoperative and postoperative analgesia.
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OBJECTIVE: Despite an increase in the rate of successful live donor renal transplantation done annually, the number of potential recipients with acceptable donors is relegated to the ever-expanding cadaver-donor waiting list due to sensitization to human leukocyte antigen (HLA) antibodies. If not sufficiently suppressed, these preformed HLA antibodies can trigger antimicrobial resistance (AMR) and early graft loss. To ameliorate this situation, various desensitization treatments are administered to provide a survival benefit to highly sensitized patients. METHOD: One hundred and six patients in the time frame of January 2017 to March 2019 were included in the study group. The desensitization protocol included therapeutic plasma exchange and administration of low-dose intravenous immunoglobulin (100 mg/kg per therapeutic plasma exchange (TPE) session) to highly sensitized patients (treatment group) who subsequently underwent renal transplantation after negative pre-transplant Centers for Disease Control and Prevention Luminex crossmatch (CDC/LumXM). We compared graft survival rates between the group undergoing desensitization (treatment group) and matched control group of patients that underwent HLA-compatible transplantation. RESULTS: In the treatment group, Kaplan-Meier analysis estimates an average rate of patient graft survival of 95.2% at 3 years post-transplant, as compared with the rate of 86.9% in the same time frame for the control-matched group (p < 0.05 for both comparisons). CONCLUSION: Desensitization treatment with TPE before live donor renal transplantation in the case of patients with HLA sensitization provides better survival benefits along with monitoring for donor-specific antibodies (DSAs) and other infections, rather than waiting for a compatible organ donor. The data lays out evidence that desensitization treatments can assist overcome HLA incompatibility barriers in live donor renal transplantation.
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BACKGROUND: Since no single test is always accurate and sensitive, two or more tests are used to increase the precision of evaluation. Different algorithms have been proposed by centers in Leiden, Basel, Vienna and Minnesota, etc. With an intention to develop an optimal algorithm for India, we evaluated pre-transplant compatibility tests for live-donor kidney transplants. Three tests complement dependent cyto-toxicity cross-match (CDCXM), flow-cytometry cross-match (FCXM) and anti-HLA antibody screening (HAS) were performed and confirmed by the anti-HLA antibody identification (HAI) assay in a multi-centric trial (three transplant centers) in India. MATERIALS AND METHODS: All prospective recipients (and their potential donors) underwent low-resolution HLA typing as well as CDCXM, FCXM and HAS assays. In addition, HAI {single antigen bead assay; (SAB)} was done for all recipients to identify possible anti-HLA antibodies. In a virtual cross-match (VXM), antibody specificity was mapped to donor HLA type to determine donor-specific antibodies (DSA). Only patients without DSA were cleared for the transplant. Alternatively, patients with DSA were offered an exchange in the kidney paired donation (KPD) program. The screening results (CDCXM, FCXM, and HAS) were analyzed, individually as well as in combination of screening assays (CDCXM+HAS, CDCXM+FCXM, and FCXM+HAS) and the results were compared with those from the HAI test. RESULTS: Out of 100 patients, 69 were males and 31 were females; 85 recipients (85%) underwent a kidney transplant. The sensitivity of CDCXM was only 12.1% and the specificity of CDCXM was 100%; whereas the sensitivity of FCXM was 84.8% and the specificity of FCXM was 89.6%. The sensitivity and specificity of class I HAS was 88.2% and 84.3%, respectively. The sensitivity and specificity class II HAS was 88.0% and 80.0%, respectively. However, when both class I/II HAS were tested together the sensitivity increased to 97.0% and the specificity to 82.1%. Similarly, the sensitivity of combined FCXM+HAS had the sensitivity of 100% and the specificity of 76.1%; CDCXM+FCXM had the sensitivity of 84.8% and the specificity of 89.6% and CDCXM+HAS assays reached 97% with the specificity of 82.1%. CONCLUSIONS: Our results showed that the algorithm of FCXM with HAS produced the best sensitivity of 100%. The specificity of 76.1% indicate that the combined FCXM+HAS assays may detect up to 24.9% false positive results. We suggest that these false-positives may be easily resolved by performing the virtual crossmatch based on HAI (SAB) results. In our reflex testing algorithmic approach only 49% patients needed HAI (SAB). Finally, our results suggested that the CDCXM assay may be discontinued in pre-transplant workup owing to its very low sensitivity (12.1%).
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Transplante de Rim , Algoritmos , Tipagem e Reações Cruzadas Sanguíneas , Feminino , Citometria de Fluxo , Rejeição de Enxerto/diagnóstico , Antígenos HLA , Teste de Histocompatibilidade , Humanos , MasculinoRESUMO
Herein, we report a highly facile and unprecedented approach to synthesize congested N-(hetero)aryl amines en route to α-amino acid amides using α-bromoamides as alkylating agents under mild reaction conditions (room temperature). The involvement of aza-oxyallyl cations as alkylating agents is the hallmark of this reaction. The method was readily adapted for the rapid synthesis of coveted 1,4-benzodiazepine-3,5-diones.
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Abstract Objective Despite an increase in the rate of successful live donor renal transplantation done annually, the number of potential recipients with acceptable donors is relegated to the ever-expanding cadaver-donor waiting list due to sensitization to human leukocyte antigen (HLA) antibodies. If not sufficiently suppressed, these preformed HLA antibodies can trigger antimicrobial resistance (AMR) and early graft loss. To ameliorate this situation, various desensitization treatments are administered to provide a survival benefit to highly sensitized patients. Method One hundred and six patients in the time frame of January 2017 to March 2019 were included in the study group. The desensitization protocol included therapeutic plasma exchange and administration of low-dose intravenous immunoglobulin (100 mg/kg per therapeutic plasma exchange (TPE) session) to highly sensitized patients (treatment group) who subsequently underwent renal transplantation after negative pre-transplant Centers for Disease Control and Prevention Luminex crossmatch (CDC/LumXM). We compared graft survival rates between the group undergoing desensitization (treatment group) and matched control group of patients that underwent HLA-compatible transplantation. Results In the treatment group, Kaplan-Meier analysis estimates an average rate of patient graft survival of 95.2% at 3 years post-transplant, as compared with the rate of 86.9% in the same time frame for the control-matched group (p < 0.05 for both comparisons). Conclusion Desensitization treatment with TPE before live donor renal transplantation in the case of patients with HLA sensitization provides better survival benefits along with monitoring for donor-specific antibodies (DSAs) and other infections, rather than waiting for a compatible organ donor. The data lays out evidence that desensitization treatments can assist overcome HLA incompatibility barriers in live donor renal transplantation.