Disseminated Mycobacterium chelonae infection in kidney transplant patients.

Mycobacterium chelonae (M. chelonae) is a member of the rapidly growing non-tuberous mycobacteria and can cause disseminated tissue infection, particularly, in the limbs. We reviewed medical records of two kidney transplant patients. We describe their background disease and transplantation details, with the use of immunosuppressive medication. We also discuss the presentation of M. chelonae infection and treatment. Both patients received deceased brain-dead donor kidney transplants for end-stage kidney disease. Both developed cutaneous manifestations of M. chelonae, progressing to disseminated infections. Case 1 was on low-dose prednisolone (2 mg) and tacrolimus, whereas, case 2 received varying doses of prednisolone (5-40 mg) and sirolimus. Antibiotics advised by infectious disease specialists were initiated within a month of skin lesion appearance. Effective treatment involved a combination of antibiotics such as clarithromycin, azithromycin, linezolid and tigecycline. These cases underline the efficacy of clarithromycin and azithromycin as long-term antibiotic treatment, with linezolid and tigecycline for management of acute dissemination.

Cystatin C as a Marker of Kidney Function in Children.

This review examines the reliability of cystatin C as a biomarker for kidney function in paediatric populations. Chronic kidney disease (CKD) affects a significant number of children globally, leading to severe health complications such as anaemia, hypertension, and growth disorders. Traditionally, kidney function has been assessed using the estimated glomerular filtration rate derived from serum creatinine, though this method is flawed due to variability in muscle mass, age, gender, and diet. Cystatin C offers an alternative as it is less influenced by these factors. Evidence from various studies indicates that cystatin C provides a more accurate assessment of kidney function, especially in neonates and children with urinary tract malformations. Additionally, it is more reliable in early detection of acute kidney injury in paediatric intensive care units. Despite its potential, cystatin C is not yet widely adopted in clinical guidelines, primarily due to a lack of large-scale paediatric studies. Nonetheless, existing research supports its utility in providing a consistent and precise measure of kidney function across different paediatric age groups, suggesting that it could enhance early diagnosis and management of CKD in children if more extensive validation studies are conducted.

Should Cystatin C eGFR Become Routine Clinical Practice?

Kidney function assessment is crucial for diagnosing and managing kidney diseases. Glomerular filtration rate (GFR) is widely used as an indicator of kidney function, but its direct measurement is challenging. Serum creatinine, a commonly used marker for estimating GFR (eGFR), has limitations in accuracy and sensitivity. Cystatin C, a protein freely filtered by the glomerulus, has emerged as a promising alternative marker for kidney function. It is unaffected by muscle mass and shows stronger associations with cardiovascular disease and mortality than creatinine. Various equations have been developed to estimate GFR using creatinine or cystatin C alone or in combination. The CKD-EPIcreat-cys equation combining both markers demonstrates improved accuracy in GFR estimation, especially for individuals with eGFR values of 45-59 mL/min/1.73 m2. Cystatin C-based estimates of GFR outperform creatinine-based estimates in predicting clinical outcomes and identifying patients at higher risk, particularly in elderly and non-white ethnic groups. Cystatin C offers advantages over creatinine as a marker of kidney function. It is not influenced by non-kidney factors and provides more accurate estimation of GFR, aiding in the early detection of kidney disease and predicting adverse outcomes. Incorporating cystatin C into routine kidney function assessment may improve patient risk stratification and guide clinical decision-making. However, widespread adoption of cystatin C testing requires increased availability and accessibility in clinical laboratories. Further research and implementation efforts are needed to fully realize the potential of cystatin C in kidney function assessment and improving patient outcomes.

The impact of e-alerts on inpatient diagnosis and management of acute kidney injury.

AIMS/BACKGROUND: Electronic alerts can help with the early detection of acute kidney injury in hospitalised patients. Evidence for their role in improving patient care is limited. The authors have completed an audit loop to evaluate the impact of electronic alerts, and an associated acute kidney injury management pathway, on patient care. METHODS: The audits were conducted at a large tertiary care hospital in the UK. Case notes were reviewed for 99 patients over two periods: pre-alert (in 2013; n=55) and post-alert (in 2018; n=44), using the same methodology. Patients for case note reviews were randomly chosen from the list of acute kidney injury alerts generated by the local laboratory information management system. RESULTS: Recognition of acute kidney injury, as documented in the case notes, increased from 15% to 43% between the two periods. Time to first medical review (following electronic alerts) improved by 17 minutes (median 4 hours 4 minutes in 2013 vs 3 hours 47 minutes in 2018). Completion of pre-defined acute kidney injury assessment tasks (review of vital signs, biochemistry and acid-base parameters, evidence of fluid balance assessment, consideration of possible sepsis, and examination or requesting urinalysis) improved in 2018. However, acute kidney injury management tasks (correction of hypovolaemia, addressing or investigating obstruction, medications review, renal referral, requesting of further biochemical tests, addressing possible sepsis) showed very little or no improvement. CONCLUSIONS: The introduction of acute kidney injury electronic alerts and management pathway resulted in improved recognition and initial assessment of patients with acute kidney injury. Further steps are needed to translate this in to improved patient management.

Synthesis and in vitro anticancer evaluation of some 4,6-diamino-1,3,5-triazine-2-carbohydrazides as Rad6 ubiquitin conjugating enzyme inhibitors.

Series of 4-amino-6-(arylamino)-1,3,5-triazine-2-carbohydrazides (3a-e) and N'-phenyl-4,6-bis(arylamino)-1,3,5-triazine-2-carbohydrazides (6a-e), for ease of readership, we will abbreviate our compound names as 'new triazines', have been synthesized, based on the previously reported Rad6B-inhibitory diamino-triazinylmethyl benzoate anticancer agents TZ9 and 4-amino-N'-phenyl-6-(arylamino)-1,3,5-triazine-2-carbohydrazides. Synthesis of the target compounds was readily accomplished in two steps from either bis-aryl/aryl biguanides via reaction of phenylhydrazine or hydrazinehydrate with key 4-amino-6-bis(arylamino)/(arylamino)-1,3,5-triazine-2-carboxylate intermediates. These new triazine derivatives were evaluated for their abilities to inhibit Rad6B ubiquitin conjugation and in vitro anticancer activity against several human cancer cell lines: ovarian (OV90 and A2780), lung (H1299 and A549), breast (MCF-7 and MDA-MB231) and colon (HT29) cancer cells by MTS assays. All the 10 new triazines exhibited superior Rad6B inhibitory activities in comparison to selective Rad6 inhibitor TZ9 that was reported previously. Similarly, new triazines also showed better IC50 values in survival assays of various tumor cell lines. Particularly, new triazines 6a-c, exhibited lower IC50 (3.3-22 µM) values compared to TZ9.

Rad6 upregulation promotes stem cell-like characteristics and platinum resistance in ovarian cancer.

Ovarian cancer is the fifth most deadly cancer in women in the United States and despite advances in surgical and chemotherapeutic treatments survival rates have not significantly improved in decades. The poor prognosis for ovarian cancer patients is largely due to the extremely high (80%) recurrence rate of ovarian cancer and because the recurrent tumors are often resistant to the widely utilized platinum-based chemotherapeutic drugs. In this study, expression of Rad6, an E2 ubiquitin-conjugating enzyme, was found to strongly correlate with ovarian cancer progression. Furthermore, in ovarian cancer cells Rad6 was found to stabilize ß-catenin promoting stem cell-related characteristics, including expression of stem cell markers and anchorage-independent growth. Cancer stem cells can promote chemoresistance, tumor recurrence and metastasis, all of which are limiting factors in treating ovarian cancer. Thus it is significant that Rad6 overexpression led to increased resistance to the chemotherapeutic drug carboplatin and correlated with tumor cell invasion. These findings show the importance of Rad6 in ovarian cancer and emphasize the need for further studies of Rad6 as a potential target for the treatment of ovarian cancer.

Emergency orthopaedic surgery under noninvasive ventilation after refusal for general anaesthesia.

In this observation, we report a novel use of noninvasive positive pressure ventilation in the operating room to support ventilation in an acidotic hypercapnic patient with severe acute chronic respiratory failure refuted for general anaesthesia, operated under spinal anaesthesia for a femoral fracture. The feasibility of noninvasive ventilatory assistance during surgery performed under regional anaesthesia is reported here. In selected cases, noninvasive ventilation can be used in the management of patients with acute or chronic respiratory failure requiring an urgent surgical intervention but in whom the respiratory status excluded a general anaesthesia.

Malaria in camps for internally-displaced persons in Uganda: evaluation of an insecticide-treated bednet distribution programme.

Malaria is a key health problem among displaced populations in malaria-endemic areas. Mass distribution of insecticide-treated bednets (ITN) to prevent malaria is often carried out in complex emergencies, but there are few data on the outcome or operational effectiveness of such programmes. In June 2001, Medecins Sans Frontieres completed a mass distribution of ITNs (Permanet) to internally displaced persons in Bundibugyo, southwest Uganda, distributing one to four nets per household, and aiming to provide coverage for all residents. In July 2002, we did a cross-sectional survey using three-stage cluster sampling to evaluate the programme. A total of 1245 individuals from 835 households were interviewed. An ITN was present in 75.6% (95% CI 72.7-78.5) of the households, but only 56.5% (95% CI 52.3-60.4) of individuals were sleeping under an ITN, and nets were often damaged. The prevalence of malarial parasitaemia was 11.2% (95% CI 9.4-13.0), and was significantly lower in ITN users compared to non-users (9.2% vs. 13.8%, relative risk [RR] 0.63, 95% CI 0.46-0.87); ITNs with severe damage remained effective (RR for severely damaged net 0.58, 95% CI 0.35-0.98). There was no significant difference in haemoglobin concentration between ITN users and non-users.