Refurbishing Pacemakers: A Viable Approach

Cardiologists implant permanent pacemakers widely for indications like sick sinus syndrome and complete heart block. The guidelines for such implantations are well established1. However, in developing countries like India, all patients who need pacemakers do not receive them because of financial constraints. Even when such patients get a pacemaker, it is often a more affordable VVI pacemaker rather than the costly DDD pacemaker. The lack of a health insurance scheme and improper social support programs prevent the more widespread implantation of appropriate pacemakers. However, in the developed countries and in affluent pockets of developing countries like India, the pacemaker implantation rates are quite high. Often permanent pacemakers are implanted in the very old and people with predicted brief longevities, due to medico-legal and other social reasons. There are quite a few instances when pacemakers are explanted within a year or even within a few months. This is often due to the unfortunate death of the patient due to unrelated causes. Such pacemakers have battery lives, which are near normal. These can be explanted from the dead patient after taking consent from the relatives and “refurbished” for use in another needy patient. Refurbishing involves proper re-sterilization, checking of battery life, pacing mode and other parameters and re-labelling with the current parameters including predicted battery life. These refurbished pacemakers are a suitable alternative for the financially ‘no option’ group of patients who otherwise would not afford a pacemaker. These can last nearly as long as the original pacemakers. Even pulse generators whose shelf lives have expired can also be resterilised and used gainfully for the economically deprived

Cardiac involvement in systemic sclerosis- a hospital-based study in tertiary health care centre in Puducherry, India

Background: Systemic sclerosis (SSc) is a complex immune-mediated condition. Systemic sclerosis related cardiac pathologies can be detected in an early stage using various imaging techniques. Aim was to study cardiac involvement in patients with systemic sclerosis. Methods: The present study was carried out as a descriptive hospital-based study of 31 patients with systemic sclerosis above 13 years of age, of either sex or who fulfilled American Rheumatism Association (ARA) diagnostic criteria. A detailed profile of lab investigations and imaging including inflammatory markers, immunological parameters, ECG and ECHO were done. Data analysis was done using SPSS (statistical package for social sciences) version 21.0. A p value <0.05 was considered statistically significant. Results: Median age of the study patients was 36 years and 90% females. Nearly 19% of the patients were classified as limited, 39% as early diffuse and 42% as late diffuse systemic sclerosis. Rheumatoid factor was positive in 19% of the patients, while antinuclear antibodies (ANA) was positive in all the patients. Pulmonary arterial hypertension (PAH) was noted in 61%. Right ventricular systolic pressure (RVSP) was relatively higher in limited SSc patients. Patients with late diffuse SSc had higher RVSP than early diffuse SSc. RV systolic function assessed by tricuspid annular plane systolic excursion (TAPSE) showed abnormally low value (<18) in five patients. Conclusions: Considerable proportion of patients with systemic sclerosis present with cardiac involvement. Tissue Doppler imaging can help in diagnosing subclinical RV dysfunction by measuring TEI index of right ventricle, which can predict PAH

Have we overlooked the role of mifepristone for the medical management of tubal ectopic pregnancy?

open access via the OUP Agreement Funding B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1176437).Peer reviewedPublisher PD

Ventricular Tachycardia in Repaired Double Chambered Right Ventricle - Identification of the Substrate and Successful Ablation

A 35 year old female presented with recurrent ventricular tachycardia 5 years after she had undergone surgical repair of double chambered right ventricle. Electroanatomical mapping showed a localised scar in the apex with double potentials and good pace map. Ablation here resulted in non-inducibility of ventricular tachycardia. We hypothesise that the scarring in the apex is the result of sustained pressure overload and becomes arrhythmogenic similar to the apical scar in patients with mid-ventricular hypertrophic cardiomyopathy

Abasic and oxidized ribonucleotides embedded in DNA are processed by human APE1 and not by RNase H2

Ribonucleoside 5'-monophosphates (rNMPs) are the most common non-standard nucleotides found in DNA of eukaryotic cells, with over 100 million rNMPs transiently incorporated in the mammalian genome per cell cycle. Human ribonuclease (RNase) H2 is the principal enzyme able to cleave rNMPs in DNA. Whether RNase H2 may process abasic or oxidized rNMPs incorporated in DNA is unknown. The base excision repair (BER) pathway is mainly responsible for repairing oxidized and abasic sites into DNA. Here we show that human RNase H2 is unable to process an abasic rNMP (rAP site) or a ribose 8oxoG (r8oxoG) site embedded in DNA. On the contrary, we found that recombinant purified human apurinic/apyrimidinic endonuclease-1 (APE1) and APE1 from human cell extracts efficiently process an rAP site in DNA and have weak endoribonuclease and 3'-exonuclease activities on r8oxoG substrate. Using biochemical assays, our results provide evidence of a human enzyme able to recognize and process abasic and oxidized ribonucleotides embedded in DNA

A comparison of DNA sequencing and gene expression profiling to assist tissue of origin diagnosis in cancer of unknown primary.

Cancer of unknown primary (CUP) is a syndrome defined by clinical absence of a primary cancer after standardised investigations. Gene expression profiling (GEP) and DNA sequencing have been used to predict primary tissue of origin (TOO) in CUP and find molecularly guided treatments; however, a detailed comparison of the diagnostic yield from these two tests has not been described. Here, we compared the diagnostic utility of RNA and DNA tests in 215 CUP patients (82% received both tests) in a prospective Australian study. Based on retrospective assessment of clinicopathological data, 77% (166/215) of CUPs had insufficient evidence to support TOO diagnosis (clinicopathology unresolved). The remainder had either a latent primary diagnosis (10%) or clinicopathological evidence to support a likely TOO diagnosis (13%) (clinicopathology resolved). We applied a microarray (CUPGuide) or custom NanoString 18-class GEP test to 191 CUPs with an accuracy of 91.5% in known metastatic cancers for high-medium confidence predictions. Classification performance was similar in clinicopathology-resolved CUPs - 80% had high-medium predictions and 94% were concordant with pathology. Notably, only 56% of the clinicopathology-unresolved CUPs had high-medium confidence GEP predictions. Diagnostic DNA features were interrogated in 201 CUP tumours guided by the cancer type specificity of mutations observed across 22 cancer types from the AACR Project GENIE database (77,058 tumours) as well as mutational signatures (e.g. smoking). Among the clinicopathology-unresolved CUPs, mutations and mutational signatures provided additional diagnostic evidence in 31% of cases. GEP classification was useful in only 13% of cases and oncoviral detection in 4%. Among CUPs where genomics informed TOO, lung and biliary cancers were the most frequently identified types, while kidney tumours were another identifiable subset. In conclusion, DNA and RNA profiling supported an unconfirmed TOO diagnosis in one-third of CUPs otherwise unresolved by clinicopathology assessment alone. DNA mutation profiling was the more diagnostically informative assay. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland