Peritoneal Dialysis Drop-out: Causes and Prevention Strategies

Peritoneal dialysis (PD) as a renal replacement therapy (RRT) has become wide spread since its inception more than twenty-five years back. Since then, several advances have been made and PD has been accepted as an alternative therapy to hemodialysis (HD), with excellent survival, lower cost, and improved quality of life. In spite of comparable survival of HD and PD, improved PD techniques over the last few years, and lower health care costs with PD, PD prevalence remains low in many countries. An important reason for the low PD prevalence is patient dropouts, that is, transfer to HD. The reasons for dropouts are multifactorial, that is, modality related, system related, and patient related. These include episodes of peritonitis, catheter-related problems, ultrafiltration failure, patient fatigue, and provider comfort. This review discusses the various factors that contribute to PD dropout and the strategies to prevent it

In Peritoneal Dialysis, Is There Sufficient Evidence to Make “PD First” Therapy?

Since its introduction more than 3 decades ago, the use of peritoneal dialysis (PD) has increased greatly due to its simplicity, convenience, and low cost. Advances in technique, antibiotic prophylaxis, and the introduction of newer solutions have improved survival, quality of life, and reduced rate of complications with PD. In Hong Kong, approximately 80% end-stage renal disease (ESRD) patients perform PD; in others, that is, Canada, Australia, and New Zealand, 20%–30% patients use PD. However, in the United States, the annual rate of prevalent patients receiving PD has reduced to 8% from its peak of 15% in mid-1980s. PD as the initial modality is being offered to far less patients than hemodialysis (HD), resulting in the current annual incidence rate of less than 10% in USA. There are many reasons preventing the PD first initiative including the increased numbers of in-center hemodialysis units, physician comfort with the modality, perceived superiority of HD, risk of peritonitis, achieving adequate clearances, and reimbursement incentives to providers. Patient fatigue, membrane failure, and catheter problems are other reasons which discourage PD utilization. In this paper, we discuss the available evidence and provide rationale to support PD as the initial renal replacement modality for ESRD patients

Predictive role of fragmented QRS in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

Objective: Fragmented QRS (fQRS), as defined by additional spikes in the QRS complex of a 12-lead electrocardiogram (ECG), is a marker of scarred myocardium. In patients with coronary artery disease (CAD), fQRS is a predictor of heart failure (HF) and other major adverse cardiac events (MACE). The study was aimed to evaluate the role of fQRS in prediction of HF in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: In a prospective, non-randomized, small observational study, we enrolled 188 consecutive patients with STEMI undergoing primary PCI. Patients were grouped according to the presence or absence of fQRS and their in-hospital, 1 and 6-month MACE outcomes were assessed. Results: Of the 188 patients, fQRS were noted in 92 (48.94%) patients. Patients with fQRS were more likely to have Killip class II/III/IV. Patients with fQRS had a significantly higher corrected QT interval, lower left ventricular ejection fraction (LVEF), and higher N-terminal pro brain natriuretic peptide (NT-pro BNP) at 24 hours and 48 hours compared to patients without fQRS. The in-hospital (P=0.001), 30-day (P=0.03) and 6-month (p=0.01) MACE were higher in patients with fQRS. On logistic multiple analysis, fQRS in anterior leads (OR=3.70, CI=1.68-10.02, p=0.001), fQRS in more than 2 leads (OR=5.20, CI=1.51-12.83, p=0.01), NT-proBNP (OR=1.05, CI=1.03-1.08, p=0.02) and Killip class II/III/IV were found to be significant predictors for HF hospitalization. Conclusion: Our findings suggest that fQRS can be a predictor for HF in patients with STEMI and provide a simple and readily available technique for predicting prognosis. Larger studies are required to validate these findings

Genome-wide expression profiling reveals transcriptomic variation and perturbed gene networks in androgen-dependent and androgen-independent prostate cancer cells.

Previously, we have developed a unique in vitro LNCaP cell model, which includes androgen-dependent (LNCaP-C33), androgen-independent (LNCaP-C81) and an intermediate phenotype (LNCaP-C51) cell lines resembling the stages of prostate cancer progression to hormone independence. This model is advantageous in overcoming the heterogeneity associated with the prostate cancer up to a certain extent. We characterized and compared the gene expression profiles in LNCaP-C33 (androgen-dependent) and LNCaP-C81 (androgen-independent) cells using Affymetrix GeneChip array analyses. Multiple genes were identified exhibiting differential expression during androgen-independent progression. Among the important genes upregulated in androgen-independent cells were PCDH7, TPTE, TSPY, EPHA3, HGF, MET, EGF, TEM8, etc., whereas many candidate tumor suppressor genes (HTATIP2, CDKN2A, CDKN2B, CDKN1C, TP53, TP73, ICAM1, SOCS1/2, SPRY2, PPP2CA, PPP3CA, etc.) were decreased. Pathway prediction analysis identified important gene networks associated with growth-promoting and apoptotic signaling that were perturbed during androgen-independent progression. Further investigation of one of the genes, PPP2CA, which encodes the catalytic subunit of a serine phosphatase PP2A, a potent tumor suppressor, revealed that its expression was decreased in prostate cancer compared to adjacent normal/benign tissue. Furthermore, the downregulated expression of PPP2CA was significantly correlated with tumor stage and Gleason grade. Future studies on the identified differentially expressed genes and signaling pathways may be helpful in understanding the biology of prostate cancer progression and prove useful in developing novel prognostic biomarkers and therapy for androgen-refractory prostate cancer

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Differential role of caspase-8 in hepatocytes and non-parenchymal liver cells in a model of chronic liver injury and progenitor cell activation

The balance between apoptosis and proliferation represents the basis for the maintenance of tissue homeostasis. Receptor mediated cell death through the activation of Caspases has been identified as an important mechanism to control life and death in various tissues. In this study, we modulated Caspase-8 activity in individual liver cell types using hepatocyte-specific knockout mice for Caspase-8 (Casp8Deltahepa) and a mouse strain for a ubiquitous deletion of Caspase-8 (Casp8DeltaMx) in the DDC (3,5-diethocarbonyl-1,4-dihydrocollidine) model of secondary sclerosing cholangitis and liver progenitor cells (LPCs) activation. Here, we demonstrate that mice with Caspase-8 inhibition in hepatocytes (Casp8Deltahepa) were protected from DDC-mediated injury, while mice with a ubiquitous conditional Caspase-8 knockout (Casp8DeltaMx) displayed a significantly enhanced hepatic inflammation and tissue injury. This was demonstrated by higher transaminases, bilirubin levels and finally also more liver fibrosis. Thereby Caspase-3 activity was reduced in both knockout strains, suggesting other mechanisms being responsible for the phenotype. Correlating with enhanced liver injury, Casp8DeltaMx mice displayed a stronger infiltration of mononuclear immune cells and more proliferation of LPCs in periportal areas. Further analysis confirmed that these infiltrating immune cells are resistant against extrinsic apoptosis. Bone marrow transplantation (BMT) experiments demonstrated that Caspase-8-deficient bone marrow derived cells are responsible for increased liver injury in DDC fed mice. Taken together, our in vitro and in vivo finding demonstrates a cell-specific and distinct impact of Caspase-8 on individual liver cell types. While a hepatocyte specific knockout provided protection from liver damage the ubiquitous deletion of Caspase-8 triggered more injury and inflammation. This phenotype was associated with a stronger ductular reaction and activation of the hepatic progenitor cell niche and caused through mechanism of immune-cell mediated liver injury

Hypertension in Cardiovascular and Kidney Disease

The relationship between hypertension and chronic kidney disease (CKD) is bidirectional in nature and, generally, management strategies for cardiovascular risk reduction also attenuate progression of CKD. Prevalent hypertension increases with diminishing kidney function, and the management strategy changes with level of kidney function. In this review, we will examine the evidence for management of hypertension, as a modifiable risk factor for cardiovascular disease in CKD, and the impact of this management on progression of CKD

A Study on Homicidal Head Injury Cases with Findings in Medicolegal Autopsy At Darbhanga Medical College & Hospital, Bihar

Introduction: Traumatic head injury (THI) is one of the prevalent causes of global death and disability. lately, head injury (HI) cases have increased in both developed and developing nations. Therefore, it is of great value to evaluate various aspects associated with head injury. Methodology: This study includes all cases of deaths pertaining to head injury, presented to the mortuary of the Darbhanga Medical College & Hospital, Darbhanga, Bihar for autopsy, over the period of one year that was from July 2018 to June 2019. Ethical approval for this study was taken with due procedure from the college ethical committee. Results: The present work reported a total of 48 cases with cause of death pertaining to head injury that reported to the Department of Forensic Medicine & Toxicology during the study period. The present work showed that the majority (43.7%) of cases was in the age group 25-49 years followed by age group of ≥ 50 years. Blunt head trauma was the most frequent type of trauma followed by multiple trauma. The least frequent was penetrating type of trauma. Conclusions: The exponentially increasing vehicle numbers, bad to traffic laws such as not keeping lane discipline driving in zigzag patterns by the public, badly maintained and congested highways, alcohol abuse and absence of knowledge of helmets and the new generation of high-speed cars are all liable for crashes

A Study of Histopathology of Lungs And Liver in Brought Dead Cases of A Tertiary Care Center of Bihar

Introduction: Autopsy is a procedure that aids to identify the changes occurring in the organs which helps to establish the cause of death and time of death. It also helps to study the ante-mortem as well as postmortem aspect of death. The importance of the study is that it highlights the pattern of various lesions in the lung and liver which are seen in the medico legal and neonatal autopsies along with histopathological examination, which were either incidental or the direct cause of the death. Methodology: A retrospective descriptive study of the medico legal autopsies was carried out in the Department of Forensic Medicine and Toxicology, Darbhanga Medical College & Hospital, Laheriasri, Bihar, India for a period of six Months that was from August 2021 to January 2022. Medico legal autopsies during that period, irrespective of age and sex, were included in this study. A total of 30 medico legal autopsies were conducted in the study period in which part of lung and liver were sent for pathological examination. Results: A total of 30 specimens of part of lung were received during the period of study. Histopathological examination was carried out in each case. Out of these, 7 specimens of lung were poorly preserved and autolyzed. Majority of the samples came from male corpses. Out of the total liver specimens (i.e., 30 cases), most of the cases on histopathological examination showed sinusoidal and vascular congestion. Grossly, these liver specimens appeared unremarkable. Conclusion: This study highlights the importance of histopathological report in lung and liver autopsy cases, especially in the cases where histopathology findings were incidental and were not considered at the time of death