Outcomes of critically ill solid organ transplant patients with COVID‐19 in the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163464/2/ajt16280.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163464/1/ajt16280_am.pd

Management of new onset loss of sense of smell during the COVID-19 pandemic - BRS Consensus Guidelines

OBJECTIVES: The primary aim of the study is to provide recommendations for the investigation and management of patients with new onset loss of sense of smell during the COVID-19 pandemic. DESIGN: After undertaking a literature review, we used the RAND/UCLA methodology with a multi-step process to reach consensus about treatment options, onward referral, and imaging. SETTING AND PARTICIPANTS: An expert panel consisting of 15 members was assembled. A literature review was undertaken prior to the study and evidence was summarised for the panellists. MAIN OUTCOME MEASURES: The panel undertook a process of ranking and classifying appropriateness of different investigations and treatment options for new onset loss of sense of smell during the COVID-19 pandemic. Using a 9-point Likert scale, panellists scored whether a treatment was: Not recommended, optional, or recommended. Consensus was achieved when more than 70% of responses fell into the category defined by the mean. RESULTS: Consensus was reached on the majority of statements after 2 rounds of ranking. Disagreement meant no recommendation was made regarding one treatment, using Vitamin A drops. Alpha-lipoic acid was not recommended, olfactory training was recommended for all patients with persistent loss of sense of smell of more than 2 weeks duration, and oral steroids, steroid rinses, and omega 3 supplements may be considered on an individual basis. Recommendations regarding the need for referral and investigation have been made. CONCLUSION: This study identified the appropriateness of olfactory training, different medical treatment options, referral guidelines and imaging for patients with COVID-19-related loss of sense of smell. The guideline may evolve as our experience of COVID-19 develops

PARP-Inhibitors in BRCA-Associated Pancreatic Cancer

Recent data suggests that treatingpatients with pancreatic cancer that express mutations in BRCA1, BRCA2, and PALB2 with chemotherapy which targets the DNA repair defect in these cells, such as platinum based therapies or PARPi [poly (ADP-ribose) polymerase inhibitor], may be more beneficial in these patients. Moreover, further data also indicates the promise of combining PARPi with conventional chemotherapy. Authors summarize the data related to PARPi in BRCA-associated pancreatic cancer that was presented at the annual meeting of ASCO 2014. Enrolment on a clinical trial for patients who fit these criteria should be encouraged.Image: Schematic representation of PARP and BRCA mediated DNA repair

Ten-year outcome of Eculizumab in kidney transplant recipients with atypical hemolytic uremic syndrome– a single center experience

Abstract Background Atypical hemolytic uremic syndrome (aHUS) can result in severe kidney dysfunction, secondary to thrombotic microangiopathy. Eculizumab has been used to treat this disorder, and has resulted in favourable outcomes in both, native and transplanted kidneys. There is limited long term follow up data in kidney transplant recipients (KTRs) who received prevention and treatment with Eculizumab. We report our long term follow up data from our center to address safety and efficacy of this therapy in KTRs. Methods We performed a retrospective analysis of KTRs between January 2009 and December 2018. Clinical diagnosis of aHUS established with presence of thrombotic microangiopathy, acute kidney injury, absence of alternate identifiable etiology. We reviewed clinical data, including genetic testing for complement factor mutations, post-transplant course, and response to therapy including therapeutic and prophylactic use of eculizumab. Results Nineteen patients with aHUS received a total of 36 kidney transplants; 10 of them had 2 or more prior kidney transplants. Median age at time of last transplant was 37 years (range 27–59), 72% were female (n = 14), 78% Caucasian (n = 15), with 61% had live donor transplant (n = 12) as the last transplant. Eculizumab prophylaxis was given to 10/19 (56%) at the time of transplantation, with no aHUS recurrence during the follow up. Median duration of follow up was 46 (range 6–237) months. Mean estimated glomerular filtration rate (eGFR) at the time of last follow up was 59.5 ml/min/m2. No infections secondary to encapsulated organisms or other major infectious complications occurred during the follow up. Conclusions Eculizumab prophylaxis is safe and effective in KTRs with aHUS. Long term follow up demonstrates that it may be possible to discontinue prophylaxis carefully in selected patients with no evidence of complement mutations. </jats:sec

Bortezomib Plus Dexamethasone As Induction Treatment Followed by Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma: A Study From India

Abstract Abstract 4584 Background and Objectives – Multiple myeloma (MM) is an incurable hematological malignancy, afflicting 25000 patients each year in India. Complete remission in myeloma is a surrogate marker for improved survival. The objective of induction regimen, using novel agents such a bortezomib, and Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) is to increase the number of patients achieving CR. Here, we report a retrospective evaluation of the efficacy and response rates of induction with Bortezomib (Velcade) plus Dexamethasone (VD Regimen) followed by APBSCT and its effect on stem cell collection and final outcome of the transplant. Methods – Ten patients with symptomatic MM who had received VD induction before stem cell collection were evaluated. VD Induction comprised of Bortezomib (1.3 mg/m2) and Dexamethasone (40 mg) administered on days 1, 4, 8, 11 for four 21-day cycles. Peripheral blood stem cell collection technique involved administration of granulocyte stimulating factor (G-CSF); 300 mg/kg administered twice daily for 5 days. Adequate number of stem cells was collected in nine patients by a single harvest. One patient required apharesis twice for adequate stem cell collection. These cells were cryo-preserved. High dose Melphalan (200 mg/m2) was given followed by stem cell transfusion. Results – The median CD34-positive stem cell count was 5.6 × 106/kg. All the patients engrafted post transplant. The median time for engraftment i.e. Absolute Neutrophil Count (ANC) &gt; 500/mL was 10 days and Platelet Count &gt; 50000/mL was 16 days. The median length of hospital stay was 21 days. They were successfully managed for fever and infections with antibiotics, antifungals and supportive treatment. Irradiated blood (median - 4 units) and platelet apharesis (median – 3 units) were given. Response was assessed according to International Myeloma Working Group uniform response criteria. After induction with VD protocol, the overall response rate (ORR) was 90%. 2 patients (20%) had a complete response (CR), 7 patients (70%) had very good partial response (VGPR) and 1 patient (10%) had progressive disease. Post – APBSCT, the patient with progressive disease achieved VGPR and 6 out of 7 patients (85.7%) with VGPR achieved CR making the total responses as 8 CRs and 2 VGPRs. Thus, ORR was 100%, including 80% CR rate and 20% VGPR rate. All patients were put on maintenance therapy, 6 patients were on thalidomide (50 mg/day) and 4 patients received lenalidomide (10 mg/day) therapy. In the analysis, the median progression-free survival (PFS) was not reached at 22 months. The median overall survival (OS) was not reached after a median follow-up of 25 months, and the 2-year OS rate was 70%. Three patients (30%) had a relapse post-APBSCT, after 5 months, 9 months and 18 months respectively. Two patients (20%) expired, one due to myeloma and the other due to unrelated cause. All three patients with renal insufficiency experienced improvement in renal function and did not require dialysis post-APBSCT. Two patients (20%) developed neuropathy and two patients (20%) developed Herpes Zoster infection due to bortezomib therapy. Conclusions – The induction regimen of bortezomib plus dexamethasone is effective and well tolerated in symptomatic myeloma patients. It significantly improves post-induction and post-transplantation CR and VGPR rates and does not affect stem cell mobilization and collection procedure. Disclosures: No relevant conflicts of interest to declare. </jats:sec