Anemia is a frequent complication in inflammatory bowel disease (IBD) patients. The etiology is multifactorial, with iron deficiency and anemia of chronic disease being the main reasons. Other causes include vitamin B12 and folate deficiency, hemolytic anemia and medications such as azathioprine and sulfasalazine. Apart from physical symptoms, it is associated with several negative outcomes, including poor quality of life, increased risk of hospital admission, increased risk of surgery and higher treatment costs. Diagnostic evaluation aims to identify the underlying cause and severity to determine the appropriate therapeutic strategy. Investigations include a complete blood count, iron indices, inflammatory markers and vitamin B12 and folate levels. Patients with iron deficiency need adequate replacement therapy to improve hemoglobin and replenish iron stores. Those with moderate to severe anemia and/or active disease need intravenous iron, while mild anemia can be treated with oral iron. Multiple parenteral iron formulations are available which differ in dose and frequency of administration. Traditional oral iron supplements are available in ferrous forms, which, although effective, are associated with gastrointestinal side effects. Newer oral iron formulations have helped reduce these adverse effects but are expensive. Anemia of chronic disease is mainly driven by the effects of inflammatory mediators on iron metabolism and erythropoiesis and treatment requires control of disease activity. Relapse of anemia after therapy is frequent; hence, patients need to be closely followed up for early detection and appropriate management. Significant advances have been made in understanding the pathophysiology of anemia in IBD and better and safer iron formulations are available. However, a significant proportion of IBD patients with anemia go undetected or untreated and there is a need for improved recognition and better management practices. This review discusses various aspects of anemia in IBD and the current approach to diagnosis and management.
Parvovirus B19 infection can rarely manifest with pure red cell aplasia in immunocompromised hosts. This case details a 48-year-old male, 11 years post kidney-pancreas transplant who was admitted with a chronic normocytic anaemia (haemoglobin 72 g/L) after being admitted four months prior with a bleeding peptic ulcer, requiring eight units of packed red blood cells. In the following months, the recipient required eight further packed red blood cell units despite normal repeat upper and lower gastrointestinal endoscopies. He had normal haematinics, with a persistent reticulocytopenia (0.3%, 7 × 109 cells/L) despite 80 μg per week of subcutaneous darbepoetin alfa. Platelet and leukocyte counts were within normal limits. Parvovirus B19 polymerase chain reaction (PCR) test result was "detected" with a low cycle threshold (Ct) value of 13 generated by real-time PCR (RT-PCR). Transfusion-transmitted parvovirus was considered due to temporal association with recent blood products, but retrospective testing demonstrated that parvovirus serology and PCR results were "not detected" pre-transfusion; and that the first "detected" PCR result occurred following the first packed red blood cell transfusion. Australian Red Cross Lifeblood was notified, and lookback investigations excluded the blood products as a route for parvovirus transmission, postulating that community acquisition was most likely. High dose intravenous immunoglobulin (IVIG total 400 mg/kg/day over 5 days) and immunosuppression reduction led to haemoglobin stability to > 80 g/L over 14 days. Treatment response was further extrapolated by a parvovirus PCR cycle threshold increase to 25, 7 days after first IVIG dose in the absence of gold standard quantitative PCR testing unavailability.
PURPOSEThere are limited data on presentation and practice patterns, survival, and factors influencing overall survival (OS) in Indian patients with metastatic colorectal cancers (mCRCs).PATIENTS AND METHODSThe current study evaluated patients from 13 institutions across India diagnosed with mCRC and treated from January 2016 to May 2022. The primary end point of the study was the estimation of median OS by the Kaplan-Meier method.RESULTSThe data of 3,009 patients were submitted, of whom 2,520 were feasible for analysis. Molecular testing for rat sarcoma virus and/or B-Rapidly Accelerated Fibrosarcoma status via the polymerase chain reaction or next-generation sequencing was conducted in 993 patients (39%). At a median follow-up of 44.6 months (95% CI, 40.8 to 48.3), the median OS for the entire cohort was 18.7 months (95% CI, 18.0 to 19.4). The presence of signet ring (SR) histology (14.65 v 19.15 months, hazard ratio [HR] 1.30 [95% CI, 1.14 to 1.48]; P < .001) and Eastern Cooperative Oncology Group performance status (ECOG PS) 2 versus ECOG PS 0 or 1 (18.0 v 22.87 months, HR 1.37 [95% CI, 1.21 to 1.55]; P < .001) predicted inferior OS, whereas the receipt of monoclonal antibodies (MAbs; 21.81 v 16.92 months, HR 0.79 [95% CI, 0.72 to 0.87]; P < .001) and exposure to greater than two lines of therapy (26.71 v 16.26 months, HR 0.56 [95% CI, 0.50 to 0.62]; P < .001) were associated with improved OS.CONCLUSIONThe current multi-institutional analysis of more than 2,500 patients with mCRC in India establishes a baseline with regard to clinicopathologic characteristics, molecular testing patterns, and survival. It recognizes the importance of impaired ECOG PS, SR histology, exposure to MAbs, and multiple lines of systemic therapeutic options as factors influencing OS.
The impact of the coronavirus disease 2019 (COVID-19) pandemic extended beyond direct infection-associated complications to wide-reaching impacts on health system including workflow disruption, enhanced telehealth utilization, labor force changes, and access to procedures. Whilst it is clear that COVID-19 can affect histopathological findings on kidney biopsy, the impact of COVID-19 pandemic on non-COVID-19 kidney disease research remains unclear. This study reviewed kidney biopsy research activity (i.e., patient consent and bio-sample collection), kidney biopsy practice and histopathological findings over the COVID-19 pandemic in an Australian metropolitan health service network of 4 hospitals between 2018 and 2023. All kidney biopsies performed at the Metro North Kidney Health Service between 2018 and 2023 were divided into pre-pandemic (2018-2019), pandemic (2020-2021) and post-pandemic (2022-2023) eras. Demographic data, consent rates, bio-sample collection rates, and procedural complications were retrospectively compared between the 3 eras. Two hundred twenty-nine kidney biopsies were performed in 2018 to 2019, 223 in 2020 to2021 and 213 in 2022 to 2023. Participant consent for research reduced from 70% to 63% between pre-pandemic to pandemic eras but quickly recovered in the post-pandemic era (68%). Bio-sample collection decreased (pre-pandemic: 50%, pandemic: 47%, post-pandemic: 38%) and did not recover in the post-pandemic era indicating the long tail effect on research activities. Although there were changes in service provision (e.g., delay in elective procedures, lockdowns), these measures were not associated with changes in biopsy number, setting, and department over the course of the pandemic. Kidney disease biomarker research activities decreased during the COVID-19 pandemic as demonstrated by reductions in biomarker study consent and sample collection. Strategies to maintain non-pandemic research need to be built into pandemic preparedness plans to preserve the momentum of discoveries which improve clinical outcomes for non-pandemic diseases; discoveries which may well end up being repurposed for pandemic-related conditions (e.g., remdesivir from Ebola research).
An increasing incidence of colorectal cancer (CRC) is being reported in developing countries, including India. Most Indian studies on CRC are retrospective and single-centered. The present study is an attempt to understand the current clinical profile and stage of newly diagnosed CRCs across multiple centers in Tamil Nadu, India. A multi-centric observational survey was conducted between September 1, 2021, and August 31, 2022, under the aegis of the Indian Society of Gastroenterology - Tamil Nadu chapter. Patients 18 years of age and older with a recent diagnosis of CRC fulfilling the inclusion criteria were prospectively recruited at the participating centers. Their demographic, clinical, biochemical, endoscopic, histopathologic, radiologic and risk factor details were systematically collected and analyzed. Across 23 centers in Tamil Nadu, 1208 patients were recruited. The male:female ratio was 1.49:1, while mean (SD) age was 57.7 (13.5) years. A majority (81.9
Adoptive T-cell immunotherapy holds great promise for the treatment of viral complications in immunocompromised patients resistant to standard anti-viral strategies. We present a retrospective analysis of 78 patients from 19 hospitals across Australia and New Zealand, treated over the last 15 years with "off-the-shelf" allogeneic T cells directed to a combination of Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK polyomavirus (BKV), John Cunningham virus (JCV) and/or adenovirus (AdV) under the Australian Therapeutic Goods Administration's Special Access Scheme. Most patients had severe post-transplant viral complications, including drug-resistant end-organ CMV disease, BKV-associated haemorrhagic cystitis and EBV-driven post-transplant lymphoproliferative disorder. Adoptive immunotherapy is well tolerated with few adverse effects. Importantly, 46/71 (65%) patients show definitive clinical improvement including reduction in viral load, clinical symptoms and complete resolution of end-organ disease. In addition, seven high-risk patients remain disease free. Based on this long-term encouraging clinical experience, we propose that a dedicated nationally funded centre for anti-viral cellular therapies should be considered to provide T cell therapies for critically ill patients for compassionate use. Adoptive T-cell immunotherapy offers promise to patients who are resistant to standard anti-viral strategies. Here the authors describe clinical observations in patients with viral complications treated with adoptive immunotherapy over the last 15 years.
Bile cultures are often sent with blood cultures in patients with acute bacterial cholangitis. To assess the yield of blood and bile cultures in patients with cholangitis and the clinical utility of bile cultures in guiding therapy. All patients diagnosed with cholangitis, based on the Tokyo 2013/2018 guidelines were recruited retrospectively over ten years. The clinical and investigation details were recorded. The results of bile and blood cultures including antibiotic sensitivity patterns were noted. The concordance of microorganisms grown in blood and bile cultures and their sensitivity pattern were assessed. A total of 1063 patients with cholangitis were included. Their mean age was 52.7 ± 14 years and 65.4
Background:The role of rapid on-site evaluation (ROSE) for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions is debatable. In this study, we aimed to compare the diagnostic yield of ROSE vs. non-ROSE in solid pancreatic lesions.Methods:This retrospective single-center study included patients undergoing EUS-FNA of solid pancreatic lesions from 2019-2021. Patients with cystic lesions, those undergoing fine-needle core biopsy, those undergoing repeat procedures, and patients with non-diagnostic smears with less than 6-month follow up were excluded. The diagnostic yield, need for repeat procedures and number of passes required with and without ROSE were analyzed in these patients.Results:Of the 111 patients included, 56 underwent ROSE. The majority of lesions were malignant in both groups (79.6% ROSE vs. 75% non-ROSE). The diagnostic yield was 96.4% in the ROSE group and 94.5% in the non-ROSE group. Repeat samples were needed in 1 ROSE and 2 non-ROSE patients. The median number of passes made was significantly fewer in the ROSE group (3.5, interquartile range - 3,4) compared with the non-ROSE group (4, interquartile range - 3,5) P=0.01. However, the frequency of procedure-related complications was similar in both groups.Conclusion:The utilization of ROSE during EUS-FNA of solid pancreatic lesions does not affect the diagnostic yield or the need for repeat samples, but reduces the number of passes needed for acquiring samples.
Measurement of graft dysfunction following kidney transplant through creatinine is well known to be impacted by many different factors. We report here a clinical scenario demonstrating the importance of dual measurement of glomerular filtration rate (GFR) based on creatinine and cystatin C while also examining within-subject variability of both tests.
AbstractObjectivesDysregulation of Epstein–Barr virus (EBV)‐specific cellular immunity has been hypothesised as one of the contributing factors in the pathogenesis of systemic lupus erythematosus (SLE). Lupus nephritis is a major risk factor for overall morbidity in SLE. Immune‐based strategies directed to EBV have been proposed as potential therapeutic strategy for SLE and lupus nephritis.MethodsAutologous EBV latent antigen‐specific CD4+ and CD8+ T cells were expanded in vitro and adoptively transferred to a lupus nephritis patient.ResultsThis adoptive immunotherapy had no immediate adverse effects, and the patient was subsequently treated with the anti‐CD20 antibody, obinutuzumab. The patient showed a reduction in anti‐dsDNA antibodies and improved glomerular filtration rate but remained nephrotic. These observations were coincident with a reduction in anti‐viral and global T‐cell activation.ConclusionTo our knowledge, this is the first report of the use of EBV‐specific adoptive immunotherapy to treat a patient with lupus nephritis.
Renal disorders are a major cause of morbidity and mortality in the world particularly in the developing world. Increasing environmental insults, poor recognition of acute and chronic renal disease, undeveloped preventive strategies, delayed and limited access to renal care, and high cost of treatment are important features in tropical regions where about 40% of the world's poorest population live. Acute renal injury occurs mainly from diarrhoeal disorders in children of the tropics where preventive strategies are effective. Tropical infections are common precipitants of glomerulonephritis. The epidemiology of parasitic infections, protozoal disorders, vector-borne diseases, and drug resistance patterns are all changing; some of these are linked directly or indirectly with global environmental changes. Particulate matter (PM2.5; ≤2.5 µm in aerodynamic diameter or smaller), ambient coarse PM (PM10; ≤10 µm in aerodynamic diameter), NO2 and CO in the atmosphere are present in large concentrations in most cities of the tropics and are inhaled to reach systemic circulation and may cause renal injury. In addition, a high incidence of chronic kidney disease is seen in regions of Sri Lanka, Latin America, and certain parts of India. The common threads to aetiology are dehydration, exposure to pesticides, and poor socioeconomic status among agricultural groups. As the economy improves with equitable distribution of benefits, and primary health is prioritized in these regions, renal health should also improve. The International Society of Nephrology has launched the 0by25 initiative in 2013 to eliminate preventable deaths from acute kidney injury (AKI) by 2025 with special emphasis on developing countries in Africa, Asia, and Latin America.
Abstract Transplant recipients with kidney disease, especially those who have diabetes and liver disease, have lower immunity and are at a higher risk for post-transplant infections while receiving maintenance immunosuppression. Cancer, infections, and cardiovascular diseases are known to negatively impact kidney transplant outcomes. However, due to marked improvements in medical management and preventive strategies, there has been a decline in mortality from infectious complications after transplantation. Infectious complications account for 19% of deaths in kidney transplantation recipients, with a standardized incidence ratio of 7.8 compared with matched general population in Australia and New Zealand. Risk factors of infections include T-cell-depleting therapy, deceased donor transplantation, older age, diabetes, female sex, and marginalized individual. However, death related to infection accounts for over 50% of deaths among kidney transplant recipients in the developing world. This chapter discusses various infections with viral, fungal, and mycobacterial organisms in kidney transplant recipients.