Improved Graft Function following Desensitization of Anti-AT1R and Autoantibodies in a Heart Transplant Recipient Negative for Donor-Specific Antibodies with Antibody-Mediated Rejection: A Case Report.

HLA donor-specific antibodies (DSAs) pre and post transplant increase the risk of antibody-mediated rejection (AMR) and lead to poor graft survival. Increasing data exist to support the involvement of non-HLA antibodies in triggering an immunological response. The development of non-HLA antibodies specific for AT1R is associated with poor clinical outcomes in orthotopic heart transplant recipients. This case presents an investigation of non-HLA antibodies in a 56-year-old female heart transplant recipient diagnosed with AMR in the absence of DSAs.

Chimerism Testing by Next Generation Sequencing for Detection of Engraftment and Early Disease Relapse in Allogeneic Hematopoietic Cell Transplantation and an Overview of NGS Chimerism Studies.

Chimerism monitoring after allogenic Hematopoietic Cell Transplantation (allo-HCT) is critical to determine how well donor cells have engrafted and to detect relapse for early therapeutic intervention. The aim of this study was to establish and detect mixed chimerism and minimal residual disease using Next Generation Sequencing (NGS) testing for the evaluation of engraftment and the detection of early relapse after allo-HCT. Our secondary aim was to compare the data with the existing laboratory method based on Short Tandem Repeat (STR) analysis. One hundred and seventy-four DNA specimens from 46 individuals were assessed using a commercially available kit for NGS, AlloSeq HCT NGS (CareDx), and the STR-PCR assay. The sensitivity, precision, and quantitative accuracy of the assay were determined using artificially created chimeric constructs. The accuracy and linearity of the assays were evaluated in 46 post-transplant HCT samples consisting of 28 levels of mixed chimerism, which ranged from 0.3-99.7%. There was a 100% correlation between NGS and STR-PCR chimerism methods. In addition, 100% accuracy was attained for the two external proficiency testing surveys (ASHI EMO). The limit of detection or sensitivity of the NGS assay in artificially made chimerism mixtures was 0.3%. We conducted a review of all NGS chimerism studies published online, including ours, and concluded that NGS-based chimerism analysis using the AlloSeq HCT assay is a sensitive and accurate method for donor-recipient chimerism quantification and minimal residual disease relapse detection in patients after allo-HCT compared to STR-PCR assay.

Guiding therapeutic plasma exchange for antibody-mediated rejection treatment in lung transplant recipients - a retrospective study.

Antibody-Mediated Rejection (AMR) due to donor-specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre-existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan-Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P = 0.0104). Statistical analyses showed that MFI in pre-TPE 1:16 diluted sera was predictive of a response to standardized protocol (R2  = 0.9182) and patient survival (P = 0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P = 0.0074) and patient survival (P = 0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.

Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder of unknown cause with no effective treatment. Cough affects up to 80% of patients with IPF, is frequently disabling, and lacks effective therapy. OBJECTIVE: To determine the efficacy of thalidomide in suppressing cough in patients with IPF. DESIGN: 24-week, double-blind, 2-treatment, 2-period crossover trial. (ClinicalTrials.gov registration number: NCT00600028) SETTING: 1 university center. PARTICIPANTS: 98 participants were screened, 24 were randomly assigned, 23 received treatment (78.3% men; mean age, 67.6 years; mean FVC, 70.4% predicted), and 20 completed both treatment periods. MEASUREMENTS: The primary end point was cough-specific quality of life measured by the Cough Quality of Life Questionnaire (CQLQ). Secondary end points were visual analogue scale of cough and the St. George's Respiratory Questionnaire (SGRQ). For all measures, lower scores equaled improved cough or respiratory quality of life. RESULTS: CQLQ scores significantly improved with thalidomide (mean difference vs. placebo, -11.4 [95% CI, -15.7 to -7.0]; P < 0.001). Thalidomide also significantly improved scores on the visual analogue scale of cough (mean difference vs. placebo, -31.2 [CI, -45.2 to -17.2]; P < 0.001). In participants receiving thalidomide, scores from the total SGRQ, SGRQ symptom domain, and SGRQ impact domain improved compared with those of participants receiving placebo. Adverse events were reported in 74% of patients receiving thalidomide and 22% receiving placebo; constipation, dizziness, and malaise were more frequent with thalidomide. LIMITATION: This was a single-center study of short duration and small sample size focused on symptom-specific quality of life. CONCLUSION: Thalidomide improved cough and respiratory quality of life in patients with IPF. A larger trial is warranted to assess these promising results. PRIMARY FUNDING SOURCE: Celgene Corporation.

Full genomic sequence of the HLA-DRB3*02:22:01 allele by single molecule real-time sequencing technology.

Full-length sequence covers the 5'-untranslated region (UTR), all introns and exons, and the 3' UTR.

Full genomic sequence of the HLA-DQB1*04:51 allele identified by next-generation sequencing.

Full-length sequence of HLA-DQB1*04:51 covers the 5'-untranslated region (UTR), all introns and exons and the 3'-UTR.

Epidural blood patch for severe postoperative intracranial hypotension.

Brain sag is a rare but serious postoperative complication after craniotomy. It is a clinical entity that refers to severe cerebrospinal fluid hypovolemia causing acute neurologic decompensation and obtundation. The established treatment is trendelenberg positioning. We present 3 cases of severe brain sag in which patients developed acute neurologic deterioration unresponsive to conventional treatment. An epidural blood patch was performed emergently to prevent further neurologic decline. The administration of epidural blood patch resulted in immediate and dramatic reversal of obtundation in each of these patients. Epidural blood patch may be a life-saving intervention in postcraniotomy patients presenting with refractory brain sag. It should be offered in patients who meet the criteria for brain sag and are unresponsive to conventional treatment modalities, despite the clinical presentation of herniation and coma.

Radiofrequency ablation of the supra-orbital nerve in the treatment algorithm of hemicrania continua.

Hemicrania continua (HC) is an uncommon primary headache disorder in which the diagnosis centers on unilaterality and its absolute responsiveness to indomethacin. We describe 3 patients with a long standing history of headache diagnosed as hemicrania continua. There was profound response to indomethacin which was limited by side effects. In one patient the therapy with indomethacin was limited secondary to co-morbidities. Initial diagnostic blockade provided significant relief of symptoms based on which radio-frequency ablation of the supraorbital nerve was performed with substantial improvement in symptoms. Traditionally, hemicrania continua has been managed exclusively with oral analgesics and is defined by its singular response to indomethacin. Radio-frequency ablation (RFA) has been reported in the literature for multiple indications. This case series is unique in that it describes 3 patients diagnosed with hemicrania continua with pain referred in the supraorbital nerve distribution, who underwent radiofrequency ablation of the supraorbital nerve with resultant resolution of headaches. Traditionally, hemicrania continua has been managed exclusively with oral analgesics and is defined by its singular response to indomethacin. This report is unique in that it describes three patients diagnosed with hemicrania continua with pain referred in the supraorbital nerve distribution who underwent radiofrequency ablation of the supraorbital nerve with resultant resolution of headaches. After the RFA medical management was minimal to none in both patients. Though the utility and cost efficacy of RFA of peripheral nerves needs to be confirmed in well-designed trials we present these cases as an example of how this minimally invasive technique can safely provide analgesia in a difficult to treat cephalgia. Moreover if precise anatomical localization of the headache is possible then diagnostic blockade of the appropriate peripheral nerve may be performed followed by radiofrequency ablation to provide potentially more sustained analgesia in patients where medical management is ineffective or poorly tolerated.

Transcutaneous electrical nerve stimulator trial may be used as a screening tool prior to spinal cord stimulator implantation.

This is a prospective pilot study looking at the utility of Transcutaneous Electrical Nerve Stimulator (TENS) trial as a screening tool prior to spinal cord stimulator (SCS) implant to identify patients who may fail a SCS trial. The accepted screening test prior to a permanent SCS implant is a SCS trial. Patients may fail the SCS trial due to several causes of which one is the inability to tolerate stimulation induced paresthesias. Twenty five patients scheduled for a SCS trial for the treatment of refractory pain secondary to Failed Back surgery syndrome underwent a TENS trial and psychological evaluation by personnel uninvolved in the SCS trial. Data was collected by personnel not involved in the SCS trial or permanent placement. Twenty patients completed the study. Data collected included area of coverage, paresthesia tolerance, pain and anxiety measured on a VAS scale. Comparability between the groups were analyzed using Pearson's correlation, Fisher Exact test and simple regression analysis. We noted a significant correlation between ability to tolerate TENS and SCS induced paresthesias. Statistically significant correlation was also noted between pre SCS trial anxiety score and high pain score during SCS trial. We conclude that there is potential applicability of a TENS trial as a non invasive screening tool which may promote cost effectiveness and decrease unnecessary procedural risks to the patient by avoiding SCS trial in select patients.