Renal function in pediatric patients with β-thalassemia major

In patients with β-thalassemia major, the most important cause of mortality and morbidity is organ failure due to deposits of iron.. In this study, the nature of the kidney injury and possible pathogenetic factors were investigated. Seventy children with β-thalassemia major and 14 age and sex-matched healthy children were involved in the study. Blood and timed urine samples were obtained for hematological and biochemical tests. The mean values of blood urea nitrogen (BUN), serum creatinine, creatinine clearance, serum sodium, urine osmolality, fractional excretion of sodium, potassium, and uric acid were not statistically different between the groups. Serum levels of potassium, phosphorus, and uric acid and the urine volume, high urinary protein to creatinine (U_P/Cr), urinary N-acetyl-β-d-glucosaminidase to creatinine (U_NAG/Cr), and urinary malondialdehyde to creatinine, (U_MDA/Cr) and the tubular phosphate reabsorption (TRP) values were statistically different between two groups (P<0.05). Increased serum levels of potassium, phosphorus, and uric acid in the patient group were attributed to the rapid erythrocyte turnover. The presence of high U_P/Cr, U_NAG/Cr and U_MDA/Cr ratios shows that in these patients with proximal renal tubular damage may be secondary to oxidative lipid peroxidation mediated by the iron overload. Received: 30 September 1999 / Revised: 19 May 2000 / Accepted: 22 May 2000     

Post-transfusion hypertension, convulsion and intracranial haemorrhage in β-thalassemia major

The haematologic disorder β-thalassemia major is common in Pakistan. We describe a patient with undiagnosed thalassemia presenting with hypertension and convulsions and found to have cerebral haemorrhage on neuro-imaging. He had been transfused 2 weeks before this illness. Our experience is similar to a few case reports described in literature that were found to have cerebral haemorrhages post-mortem after a similar clinical presentation. All patients had a blood transfusion within 2 weeks prior to the presentation so association with transfusion has been proposed. We have reviewed the several mechanisms presented and discussed the findings.     

Circulating osteoprotegerin and receptor activator of NF-κB ligand system in patients with β-thalassemia major

Osteoporosis represents an important cause of morbidity in patients with β-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-κB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age ± SEM, 24.26 ± 1.29 years; range, 13–41 years) and females (n = 31; age, 24.59 ± 0.95 years; range, 12–34 years) with β-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 ± 0.12 vs. 3.25 ± 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 ± 0.03 vs. 0.295 ± 0.046, respectively; P < 0.05). s-RANKL correlated negatively with age (r = −0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = −0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in β-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.     

Renal function in children with β-thalassemia major and thalassemia intermedia

In beta-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies demonstrating proteinuria, aminoaciduria, low urine osmolality, and excess secretion of the tubular damage markers, such as urinary N-acetyl-D-glucosaminidase (U(NAG)) and beta2 microglobulin, in patients with thalassemia. The object of this study was to analyze renal tubular and glomerular function in pediatric patients with beta-thalassemia and to correlate the renal findings to iron overload. Thirty-seven patients with beta-thalassemia major and 11 with thalassemia intermedia were studied. Twelve children without iron metabolism disorders or renal diseases served as a control group. No difference in blood urea nitrogen (BUN), serum creatinine, creatinine clearance, electrolytes, fractional excretion of sodium and potassium, and tubular phosphorus reabsorption was found. Serum uric acid was equal in the two groups, but its urine excretion was significantly higher in the thalassemic group. U(NAG) and U(NAG) to creatinine ratio (U(NAG/CR)) were elevated in all patients with thalassemia compared with the control group (p < 0.001) and were directly correlated to the amount of transfused iron but not to actual ferritin level. We found that renal tubular function is impaired in children with beta- thalassemia major and intermedia. It is not known whether these functional abnormalities would have any long-term effects on the patients. Further studies are needed, and means of preventing these disturbances should be sought.     

Laterality of deep venous thrombosis among trauma patients: are we screening our patients adequately?

OBJECTIVES: Major trauma represents a significant risk for development of deep venous thrombosis (DVT). Duplex ultrasonography is a noninvasive test to identify DVT and has been suggested for screening asymptomatic high-risk trauma patients. While some risk factors for DVT are well described, it remains unclear whether site of DVT development is associated with anatomical location of injury. An association between anatomical locations of injury would serve to highlight the importance of directed screening of those extremities at highest risk. Therefore, we hypothesize that location of DVT correlates with side of lower extremity injury. METHODS: We performed an 11-year (1995-2005) retrospective review from the prospectively collected trauma registry at an urban, university-based, level I trauma center. All trauma patients with lower extremity DVT were included. Lateralizing lower extremity injuries were defined as penetrating or blunt injuries affecting only one lower extremity. Fisher's exact test compared concordance between side of injury and side of DVT. RESULTS: A total of 6674 trauma patients were admitted, of whom 40 (0.6%) were diagnosed with lower extremity or pelvic DVT. Mean age of patients with DVT was 39 y, with 80% male, 80% African American, and 55% penetrating trauma. Fourteen patients (35%) with DVT sustained lateralizing lower extremity injuries (6 gunshot wounds, 5 tibia/fibula fractures, 2 femur fractures, and 1 calcaneus fracture). Twelve of these 14 patients (86%) developed DVT on the same side as their injury; (7/7 on right side and 5/7 on left side, P = 0.02). The 26 patients without lateralizing injuries had equal distribution of DVT (39% right, 42% left, and 19% bilateral). CONCLUSION: Patients who sustained lateralizing lower extremity injury and developed lower extremity DVT had a high likelihood of developing their DVT on the same side as their injury. A larger multi-institutional analysis is needed to assess the correlation between injury site and anatomical location of DVT before suggesting any changes in recommendations for duplex screening.     

Environmental risks of Pseudomonas aeruginosa–What to advise patients and parents

Pseudomonas aeruginosa (PsA) is commonly found in soil and water so is impossible to avoid completely. Parents/carers of children with cystic fibrosis (CF) are concerned about them acquiring PsA from the environment, and different families view risk differently. Our ethos is to enable children with CF to take part as much as possible in educational and fun home activities, in order to maintain their quality of life (and their family's), and not have them feel different from other children. This review presents advice for families as to what they must definitely avoid, what they must take precautions with but can allow, and what they must not avoid. It is mostly evidence-based, but where evidence is lacking it a consensus view from the Paediatric CF Unit at the Royal Brompton Hospital.     

Burn patients,parents and doctors; are we in agreement?

Background

Burns in children present a serious challenge for patients, parents and doctors. This study aimed to investigate differences in desire for burn reconstruction in paediatric patient, parent and surgeon groups.

Methods

This study is a case series (n = 21). Questionnaires were administered to patients, their parents and surgeons. Medical records were also reviewed. Data were analysed to ascertain how different factors affected desire for reconstruction between parents, patients and surgeons.

Results

Surgeons and parents were more likely to desire surgery than paediatric patients (76.2 vs 61.9 vs 52.4% respectively). Surgeons were more likely to recommend surgery for pre-pubescent patients (81.8 vs 70%). All groups were more likely to desire surgery for female patients. Patients and parents desired surgery more for hidden scars. Higher VSS scores were associated with a higher desire for surgery in all groups. Agreement between patients and parents was highest (Kappa = 0.81) with poor-moderate agreement between surgeons, patients and parents (Kappa = 0.12–0.24).

Conclusions

This study suggests that paediatric patients are less likely to want burn reconstruction compared to parents and surgeons. Gender and age may impact on desire for surgery. Opportunities for improving patient, parent and surgeon agreement may exist. Further research is warranted to validate these results.     

Distribution of Ambler class A, B and D β-lactamases among Pseudomonas aeruginosa isolates

Objectives

We determined the prevalence rate of classes A, B and D β-lactamases among extended-spectrum cephalosporin (ESC)-non-susceptible Pseudomonas aeruginosa clinical isolates from burned patients.

Methods

Disc susceptibility testing was performed on 156 P. aeruginosa isolates collected during 2010 at Prince Salman Hospital in Riyadh, Saudi Arabia. Phenotypic screening of ESBLs and MBLs in the isolates resistant to ceftazidime (MIC > 8 mg/L) was carried out. Genes encoding ESBLs and MBL were sought by PCR in ESBL- and MBL-producing isolates.

Results

The resistance rate to ceftazidime was 22.43%. The resistance rates for ESC-non-susceptible P. aeruginosa isolates to piperacillin, piperacillin/tazobactam, cefepime, aztreonam, imipenem, amikacin, gentamicin and ciprofloxacin were 100%, 71.14%, 88.57%, 48.57%, 70.0%, 82.5%, 87.5%, and 90.0% respectively. No resistance was detected to polymyxine B. The prevalence of ESBL and MBL in ESC-non-susceptible P. aeruginosa was 69.44% and 42.85%, respectively. The prevalence of structural genes for VEB-1, OXA-10 and GES ESBLs in P. aeruginosa was 68%, 56% and 20%, respectively. VIM gene was detected in 15 (100%) of MBL-producing isolates. OXA-10 like gene was concomitant with VEB, GES and/or VIM. Eight isolates harbored OXA-10 with VEB (imipenem MIC 6–8 mg/L), while five isolates harbored OXA-10 with VIM (imipenem MIC ≥ 32 mg/L) and one isolate contained OXA-10, VEB and GES (imipenem MIC 8 mg/L). PER was not detected in this study.

Conclusion

VEB-1 and OXA-10 are the predominant ESBL genes and bla_VIM is the dominate MBL gene in ESC-non-sensitive P. aeruginosa isolates in Saudi Arabia. VEB, OXA-10 and GES ESBLs have not been reported previously in Saudi Arabia and GES has not been reported previously in Middle East and North Africa.     

Optimisation of pre-operative anaemia in patients before elective major surgery – why,who, when and how?

Anaemia in surgical patients is a common and serious problem; around 40% of patients presenting for major surgery are anaemic. Patients with pre-operative anaemia have significantly higher rates of morbidity and mortality and are likely to be transfused red cells. In addition, red cell transfusions are independently associated with worse outcomes. Pre-optimisation of anaemia in surgical patients leads to higher pre-operative haemoglobin concentrations and less need for transfusion. Patients undergoing major surgery (defined as blood loss > 500 ml expected or possible) should be optimised if their haemoglobin concentration is less than 130 g.l⁻¹ on screening. Detection of anaemia should follow listing for surgery as soon as possible to allow enough time for optimisation. The most common cause of pre-operative anaemia is iron deficiency, which can be treated with iron therapy. Iron clinics should be set up in either primary or secondary care to allow for optimal treatment. In this review, we present literature supporting the optimisation of pre-operative anaemia and propose a treatment algorithm.     

Möbius and Möbius-like patients: etiology,diagnosis, and treatment options

The surgical goal in Mobius patients is far more modest and differs from patients with unilateral developmental facial paralysis. It is impossible to restore a true smile in these mask-like, expressionless faces. Despite sophisticated microneurovascular transplantations, movement can only be restored along one vector and enhanced firmness in the cheeks, thus multiple differentiated facial animation is not achievable. A detailed neurological evaluation can identify possible motor donors or residual function, which can be used for additional dynamic restorations. Due to the multiple cranial nerve involvement a thorough clinical and electrophysiological examination is mandatory. In addition, electromyographic survey of the potential motor donors is very helpful to avoid weak wasted regeneration and prevent further downgrading of function. Because of the variety of cranial nerves involved in M?bius' syndrome, a standard procedure for dynamic restoration cannot and should not be promoted; instead, a careful preoperative objective and quantitative assessment should guide the reconstructive surgeon to the optimal reconstruction strategy. Useful movement can be restored in afflicted patients that may signal physical and psychological rehabilitation.     

β-defensins and the epididymis: contrasting influences of prenatal,postnatal, and adult scenarios

β-defensins are components of host defense, with antimicrobial and pleiotropic immuno-modulatory properties. Research over the last 15 years has demonstrated abundant expression of a variety of β-defensins in the postnatal epididymis of different species. A gradient of region- and cell-specific expression of these proteins is observed in the epithelium of the postnatal epididymis. Their secretion into the luminal fluid and binding to spermatozoa as they travel along the epididymis has suggested their involvement in reproduction-specific tasks. Therefore, continuous attention has been given to various β-defensins for their role in sperm function and fertility. Although β-defensins are largely dependent on androgens, the underlying mechanisms regulating their expression and function in the epididymis are not well understood. Recent investigation has pointed out to a new and interesting scenario where β-defensins emerge with a different expression pattern in the Wolffian duct, the embryonic precursor of the epididymis, as opposed to the adult epididymis, thereby redefining the concept concerning the multifunctional roles of β-defensins in the developing epididymis. In this review, we summarize some current views of β-defensins in the epididymis highlighting our most recent data and speculations on their role in the developing epididymis during the prenatal-to-postnatal transition, bringing attention to the many unanswered questions in this research area that may contribute to a better understanding of epididymal biology and male fertility.     

Changes of haemostasis in patients undergoing major abdominal surgery--is there a difference between elderly and younger patients?

Many physiological functions are altered in the elderly. Itis not clear whether this applies to haemostatic mechanismsin patients undergoing major surgery. Twenty-five consecutivepatients <60 yr and 25 consecutive patients >70 yr scheduledfor abdominal surgery for malignancies were included in ourstudy. Various standard coagulation variables and specific markersof coagulation were serially measured before surgery (baseline),at arrival on the intensive care unit (ICU), 4 h after arrivalon ICU, and on the morning of the first postoperative day. Plateletfunction was assessed using the Platelet Function Analyser PFA-100^TMwith adenosine diphosphate (ADP) as an inductor. Anaesthesiaand surgery were similar between the elderly (76(3) years) andyounger (53(5) years) groups. Baseline plasma levels of prothrombinfragments F1+2, thrombin-antithrombin III (TAT) complex, andD-dimers were significantly different between the two groups,indicating thrombin activation and fibrin formation in the elderly.Postoperatively, only F1+2 plasma levels were significantlyhigher in the elderly (4.0(0.8) nmol/l) than in the youngerpatients (2.2(0.9) nmol/l), whereas the course of D-dimer andTAT did not differ significantly between the two groups. Endothelial-derivedmarkers of coagulation (von Willebrand factor, collagen-bindingactivity of von Willebrand factor) were not different betweenthe groups throughout the study period. Platelet function wasimpaired in the elderly compared with the younger patients.It is concluded that elderly patients showed more prothrombinactivation/thrombin generation and increased fibrinolytic activityprior to surgery than younger patients. However, perioperativechanges of coagulation in the elderly were similar to thoseseen in younger patients. Br J Anaesth 2001; 87: 435–40     

Timing of major fracture care in polytrauma patients – An update on principles,parameters and strategies for 2020

ObjectivesSustained changes in resuscitation and transfusion management have been observed since the turn of the millennium, along with an ongoing discussion of surgical management strategies. The aims of this study are threefold: a) to evaluate the objective changes in resuscitation and mass transfusion protocols undertaken in major level I trauma centers; b) to summarize the improvements in diagnostic options for early risk profiling in multiply injured patients and c) to assess the improvements in surgical treatment for acute major fractures in the multiply injured patient.MethodsI. A systematic review of the literature (comprehensive search of the MEDLINE, Embase, PubMed, and Cochrane Central Register of Controlled Trials databases) and a concomitant data base (from a single Level I center) analysis were performed. Two authors independently extracted data using a pre-designed form. A pooled analysis was performed to determine the changes in the management of polytraumatized patients after the change of the millennium.II. A data base from a level I trauma center was utilized to test any effects of treatment changes on outcome. Inclusion criteria: adult patients, ISS > 16, admission < less than 24 h post trauma. Exclusion: Oncological diseases, genetic disorders that affect the musculoskeletal system. Parameters evaluated were mortality, ICU stay, ICU complications (Sepsis, Pneumonia, Multiple organ failure).ResultsI. From the electronic databases, 5141 articles were deemed to be relevant. 169 articles met the inclusion criteria and a manual review of reference lists of key articles identified an additional 22 articles.II. Out of 3668 patients, 2694 (73.4%) were male, the mean ISS was 28.2 (SD 15.1), mean NISS was 37.2 points (SD 17.4 points) and the average length of stay was 17.0 days (SD 18.7 days) with a mean length of ICU stay of 8.2 days (SD 10.5 days), and a mean ventilation time of 5.1 days (SD 8.1 days).Both surgical management and nonsurgical strategies have changed over time. Damage control resuscitation, dynamic analyses of coagulopathy and lactate clearance proved to sharpen the view of the worsening trauma patient and facilitated the prevention of further complications. The subsequent surgical care has become safer and more balanced, avoiding overzealous initial surgeries, while performing early fixation, when patients are physiologically stable or rapidly improving. Severe chest trauma and soft tissue injuries require further evaluation.ConclusionsMultiple changes in management (resuscitation, transfusion protocols and balanced surgical care) have taken place. Moreover, improvement in mortality rates and complications associated with several factors were also observed. These findings support the view that the management of polytrauma patients has been substantially improved over the past 3 decades.     

Pathophysiology,diagnosis, and treatment of methylmalonic aciduria—recent advances and new challenges

Classical methylmalonic aciduria is a relatively rare inborn error of branched-chain amino acid metabolism, occurring in 1:50,000 to 1:80,000 newborns. Three decades after its recognition, major progress has been made in survival and prevention of neurological sequelae in affected children, if the diagnosis is made early and treatment and follow-up care are meticulous. Therapy consists of a specially formulated protein diet, carnitine supplementation, and vigorous emergency treatment during intercurrent illnesses aimed at preventing the development of catabolism. Recently the clinician has been challenged by partially unexpected long-term complications. These include chronic neurological symptoms, specifically an extrapyramidal movement disorder caused by progressive destruction of the basal ganglia, which are similar to those observed in other organic acid disorders, such as propionic aciduria or glutaric aciduria type I. Unexpected and unique is the development of chronic renal failure in a major subset of patients. As the pathophysiological basis of renal failure is still obscure, no causative treatment is available and hemodialysis may become necessary. Experience with transplantation of liver, kidney, or kidney and liver is very limited and allows as yet no conclusions. Interdisciplinary research efforts in this field should reveal new pathophysiological links and hopefully provide additional therapeutic approaches.