Novel techniques in the diagnosis, monitoring and outcome of renal and cardiac amyloidosis

Background: Systemic amyloidosis is a rare, progressive and fatal disorder of protein folding, treatment of which requires definitive amyloid fibril typing. Cardiac and renal involvement are common and are not only leading causes of mortality and morbidity, but also give rise to major challenges, complications and adverse effects of therapies aiming to suppress amyloid fibril precursor protein production. Aims: To refine and improve diagnosis, typing and management of patients with amyloidosis, through: proteomic analysis; development of novel biomarker-based risk stratification in patients with cardiorenal syndrome; evaluation of changes in body composition and cardiac dysfunction during and after systemic chemotherapy; and measures to support amyloidotic organ function. Results and Conclusions: I confirmed and extended previous studies demonstrating that proteomic analysis of amyloidotic tissue is superior overall to IHC for typing amyloid, but identified important limitations relating to certain tissues and amyloid types. I characterised the complex combined cardiac and renal phenotypes that occur in one third of patients with AL amyloidosis, and performed new analyses of biomarkers that are widely used to guide chemotherapy. Very encouragingly I have shown that rapid and deep clonal responses to chemotherapy can result in meaningful improvements in patient and renal survival in individuals with advanced kidney disease, which has previously been considered beyond salvage. Heart and kidney dysfunction both cause ECV overload and sarcopenia, which cannot be quantified clinically but contribute to poor outcomes. I used bioimpedence vector analysis to comprehensively estimate body composition at diagnosis and to aid clinical assessment during treatment. Despite these improvements in clinical monitoring and in chemotherapy generally, sudden cardiac death is common in amyloidosis. Sadly, ICD implantation in 15 patients described in my final chapter failed to translate into clinical benefit. Patients with amyloidosis continue to have unmet needs, many of which stem from heart and kidney involvement, but outcomes are gradually improving

An Acute Case of Herpes Zoster Ophthalmicus with Ophthalmoplegia

Herpes zoster ophthalmicus (HZO) with oculomotor nerve involvement is rare, even rarer as an acute presentation rather than sequelae of HZO. In this paper we present a case of cutaneous HZO in which our patient's initial presentation was one of complete ophthalmoplegia

Cardiac transplantation in transthyretin amyloid cardiomyopathy: Outcomes from three decades of tertiary center experience

Aims: Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive and fatal cardiomyopathy. Treatment options in patients with advanced ATTR-CM are limited to cardiac transplantation (CT). Despite case series demonstrating comparable outcomes with CT between patients with ATTR-CM and non-amyloid cardiomyopathies, ATTR-CM is considered to be a contraindication to CT in some centers, partly due to a perceived risk of amyloid recurrence in the allograft. We report long-term outcomes of CT in ATTR-CM at two tertiary centers. Materials and methods and results: We retrospectively evaluated ATTR-CM patients across two tertiary centers who underwent transplantation between 1990 and 2020. Pre-transplantation characteristics were determined and outcomes were compared with a cohort of non-transplanted ATTR-CM patients. Fourteen (12 male, 2 female) patients with ATTR-CM underwent CT including 11 with wild-type ATTR-CM and 3 with variant ATTR-CM (ATTRv). Median age at CT was 62 years and median follow up post-CT was 66 months. One, three, and five-year survival was 100, 92, and 90%, respectively and the longest surviving patient was Censored > 19 years post CT. No patients had recurrence of amyloid in the cardiac allograft. Four patients died, including one with ATTRv-CM from complications of leptomeningeal amyloidosis. Survival among the cohort of patients who underwent CT was significantly prolonged compared to UK patients with ATTR-CM generally (p < 0.001) including those diagnosed under age 65 years (p = 0.008) or with early stage cardiomyopathy (p < 0.001). Conclusion: CT is well-tolerated, restores functional capacity and improves prognosis in ATTR-CM. The risk of amyloid recurrence in the cardiac allograft appears to be low

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Diagnostic accuracy and safety of rigid medical thoracoscopy in undiagnosed pleural effusion and ILD: Retrospective study of 100 patients

Aim of study: A retrospective study of diagnostic evaluation, safety and thoracoscopic findings in 100 cases was done at thoracoscopy unit of Chest Department Mansoura University Hospitals in the last two years. Results: We studied 100 patients in two groups, first group (G1) consisted of 85 male patients (67.1%) with undiagnosed pleural effusion and the second group (G2) consisted of 15 undiagnosed ILD female patients (60%). Final histopathologic diagnosis in the first group revealed metastatic adenocarcinoma in 35.3%, para-pneumonic 44.7%, TB 10.6%, NHL7.1% and mesothelioma 2.4%, while in the second group it was metastatic adenocarcinoma 6.7%, UIP 46.7%, NSIP 13.3%, TB 6.7%, BAC 13.3%, silicosis 6.7% and lastly LIP in 6.7%. We found that time of ICT removal was significantly lower in the first group with p value 0.001 and complication incidences were variants; fistula was significantly lower in the first group while empyema and surgical emphysema were significantly higher in the first group with p value 0.001. Conclusion: VAMT is a good tool for the diagnosis of undiagnosed pleural diseases and is promising in ILDs, safe, and inexpensive with minimally tolerable complications

CT-guided biopsy versus conventional Abram’s needle biopsy in malignant pleural effusion

Objective: We aimed to evaluate CT guided biopsy (CTGB) vs. standard closed pleural biopsy (CPB) in the histopathological diagnosis of the type of malignancy in patients with malignant pleural effusion. Patients and methods: We studied 31 patients (21 male and 10 female) with malignant pleural effusion diagnosed by aspiration cytology and admitted to the medical ward of a general teaching hospital over a period of 1 year. Patients were randomized into two groups: group 1 (n = 16) underwent CTGB biopsy and group 2 (n = 15) underwent Abram’s CPB. The diagnostic yield of both methods was compared. Results: The mean age of patients was 54 ± 16 years. History of smoking was obtained in 15 (48.4%) patients. Dyspnea was reported in 22 (71%) and chest pain in 15 (48.4%). Malignant pleural effusion was left-sided in 17 (54.8%), and massive in 21 (67.7%) patients. Of note, CT imaging revealed parietal pleura as a tumor site in 20 (64.5%) patients. Pathological diagnosis of the type of malignancy was achieved in 14 (87.5%) of group 1 using CTGB and 6 (40%) of group 2 patients using Abram’s CPB. The diagnostic value of CTGB was significantly higher than CPB (P = 0.009). Conclusion: CT-guided biopsy was found to be a reliable and safe method in the histopathological diagnosis of malignant pleural effusion. Its diagnostic potential was much superior to the standard closed pleural biopsy

Resistant Hypertension Trials and Tribulations

© 2018 American Heart Association, Inc. In summary, I have presented a case of a patient with true resistant hypertension. We have discussed how to optimize her medical management as well as investigations of secondary causes, particularly primary aldosteronism. We have also discussed the evidence base for RDN and the deficiencies of the original SYMPLICITY trials. Several lessons have been learned about the design and conduct of clinical trials in this field that are now being implemented to definitively assess the efficacy of this approach.status: publishe

Resistant Hypertension: Trials and Tribulations

No abstract available