The natural history of renal function following orthotopic heart transplant

BACKGROUND: The outcome of solid organ transplantation has dramatically improved after the introduction of the calcineurin inhibitor cyclosporine. With the increasing longevity of heart transplant recipients, the long-term effects of cyclosporine on renal function have become more evident. The natural history of kidney function following orthotopic heart transplant is not well defined and long-term follow up studies are scant. METHODS: We conducted an observational study on patients who received a heart transplant at Saint Louis University Hospital between January 1, 1983 and December 31, 1988. Patients were followed up for 15 yr or until death whichever occurred first. In order to assess the effect of heart transplantation and cyclosporine exposure on long-term renal function we restricted the statistical analysis to patients who survived the first year post-transplantation. RESULTS: A total of 68 patients received orthotopic heart transplants at Saint Louis University Hospital between 1983 and 1988. Forty-eight (71%) patients survived for more than 1 yr. All patients were treated with cyclosporine based triple immunosuppressive regimen, with gradual cyclosporine dose reduction over time. The mean duration of follow-up was 8 yr. The estimated GFR at 5 and 10 yr post-transplant were significantly lower than estimated GFR at baseline and 1 yr post-transplant. There was no significant difference between estimated GFR at 15 yr and estimated GFR at baseline or 1 yr post-transplant. The cumulative incidence of chronic renal failure (GFR < or = 29 mL/min/1.73 m2) at 5, 10 and 15 yr was 4.2, 10.4 and 12.5%, respectively (p < 0.05). The cumulative incidence of severe chronic renal failure (GFR < or = 15 mL/min/1.73 m2) at 5, 10 and 15 yr was 2.1, 8.3 and 8.3%, respectively. The mortality rate was 8, 37, and 52% at 5, 10, and 15 yr, respectively. The 10 and 15 yr survivors had an estimated GFR at 1 yr post-transplant that was significantly higher than the non-survivors. Age, pre-transplantation estimated GFR, pre-transplantation diabetes and pre-transplantation hypertension are risk factors associated with > or = 10 mL/min/1.73 m2 decrement in estimated GFR. CONCLUSION: Heart transplant survivors beyond the first year post-transplant have a significant decrease in renal function and significant mortality observed over time. Age, pre-transplant GFR, pre-transplant diabetes and pre-transplant hypertension are important risk factors for decrement in renal function.     

Predictors of laparotomy and mortality in polytrauma patients with pelvic fractures

Background

The decision to perform laparotomy in blunt trauma patients is often difficult owing to pelvic fractures; however, once the decision is made, delay or failure to perform laparotomy could affect morbidity and mortality. We sought to identify predictors of laparotomy and mortality in polytrauma patients with pelvic fractures.

Methods

We divided 390 blunt polytrauma patients (Injury Severity Score [ISS] ≥ 16) with pelvic fractures into laparotomy (n = 56) and nonlaparotomy (n = 334) groups. We assessed the role of the following variables in predicting laparotomy and mortality: age, sex, hypotension, fluid and blood transfusions, positive abdominal computed tomography (CT) scans or focused assessment with sonography for trauma (FAST) examination, pelvic fracture severity and ISS. We analyzed the data using Student t and χ² tests, followed by logistic regression analysis.

Results

Mortality was higher in the laparotomy group than the nonlaparotomy group (28.6% v. 12.9%; overall mortality 15.1%). The laparotomy group had higher mean ISS (36.9 v. 24.9), higher mean abbreviated injury scores (AIS) for the abdomen (2.6 v. 0.9) and chest (3.4 v. 1.6), lower mean initial hemoglobin levels (105.2 v. 127.0 g/L), higher mean crystalloid (4249 v. 3436 mL) and blood transfusion volumes over 4 hours (12.1 v. 3.9 units), more frequent hypotension (44.6 v. 18.0%) and a higher percentage of positive CT scans (67.9% v. 28.4%) and FAST examination results (42.9% v. 3.3%) than the nonlaparotomy group. Age (mean 53.7 v. 41.5 yr); ISS (mean 39.0 v. 24.4); AIS for the head (mean 3.2 v. 1.7), abdomen (mean 1.6 v. 1.1), chest (mean 2.7 v. 1.8) and pelvis (mean 3.1 v. 2.6); crystalloid (mean 5157.3 v. 3266.4 mL) and blood transfusion volumes over 4 hours (mean 13.1 v. 3.7) and initial hypotension (61% v. 14.8%) were all greater among patients who died than those who survived. Mean initial hemoglobin levels were lower among patients who died than among those who survived (111.1 v. 126.2 g/L). Age, the AIS for the head, initial hypotension and low initial hemoglobin levels were highly predictive of mortality, whereas low initial hemoglobin levels, a positive FAST examination and high AIS for the abdomen and chest were all highly predictive of laparotomy.

Conclusion

Among the polytrauma patients with pelvic fractures, 14.3% underwent laparotomy, and mortality was higher among these patients than among those who did not have the procedure. The predictors of laparotomy and mortality are similar to those anticipated in patients without pelvic fractures.     

Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a major therapeutic target in a range of chronic inflammatory disorders characterised by a Th1 type immune response in which TNFalpha is generated in excess. By contrast, asthma is regarded as a Th2 type disorder, especially when associated with atopy. However, as asthma becomes more severe and chronic, it adopts additional characteristics including corticosteroid refractoriness and involvement of neutrophils suggestive of an altered inflammatory profile towards a Th1 type response, incriminating cytokines such as TNFalpha. METHODS: TNFalpha levels in bronchoalveolar lavage (BAL) fluid of 26 healthy controls, 42 subjects with mild asthma and 20 with severe asthma were measured by immunoassay, and TNFalpha gene expression was determined in endobronchial biopsy specimens from 14 patients with mild asthma and 14 with severe asthma. The cellular localisation of TNFalpha was assessed by immunohistochemistry. An open label uncontrolled clinical study was then undertaken in 17 subjects with severe asthma to evaluate the effect of 12 weeks of treatment with the soluble TNFalpha receptor-IgG1Fc fusion protein, etanercept. RESULTS: TNFalpha levels in BAL fluid, TNFalpha gene expression and TNFalpha immunoreative cells were increased in subjects with severe corticosteroid dependent asthma. Etanercept treatment was associated with improvement in asthma symptoms, lung function, and bronchial hyperresponsiveness. CONCLUSIONS: These findings may be of clinical significance in identifying TNFalpha as a new therapeutic target in subjects with severe asthma. The effects of anti-TNF treatment now require confirmation in placebo controlled studies.     

Outcome of surgery for parotid tumours: 5-year experience of a general surgical unit in a teaching hospital

BACKGROUND: Most of the recent reports on the surgical management of parotid gland disorders come from specialist divisions of otolaryngology, head and neck, or faciomaxillary surgery. The aim of the present study was to evaluate the outcome of surgery for parotid tumours in a general surgical unit of a teaching hospital. METHOD: A prospective clinicopathological study was undertaken over a 5-year period for consecutive patients operated on for parotid gland tumours in the King Saud University Unit of Riyadh Medical Complex. Parameters analyzed were demographic details, clinical presentation, diagnostic work-up, type of surgery, and outcome in terms of early and late morbidity. RESULTS: Thirty seven parotid operations were performed on 36 consecutive patients. All patients presented with parotid gland swelling. Mean age was 51.6 years with a male preponderance. Fine-needle aspiration diagnosed the pathology in 33 out of 37 lesions. Pleomorphic adenoma was the commonest pathology observed in 24 patients (64.9%). Warthin's tumour was more common among male patients and was the only pathology with bilateral involvement. Malignant tumour was found in five patients (13.5%). Superficial conservative parotidectomy was the most frequently performed operation (84%). Overall postoperative morbidity was 13.5%. Transient facial nerve palsy was observed in seven cases (19%). There was no recurrence identified in patients with benign diseases during the mean follow up of 38.5 months. CONCLUSION: Parotid gland surgery can still be performed in a general surgery unit with comparable outcome. However, the operation should be performed in units with special interest and experience in surgery for parotid gland disorders.     

Considerations on in vitro and in vivo magnetic nanoparticles hemocompatibility testing

The aim of this paper is to summarize few aspects and underline some difficulties that hemocompatibility testing come up. The purpose of hemocompatibility testing is to look for possible undesirable changes in the blood caused directly by a medical device, by chemicals leaching from a device or biomaterials. Undesirable effects of device materials on the blood may include alterations in coagulation parameters, thrombus formation, hemolysis, and immunological changes. For each different event the literature is rich in showing tests, not different in principle, but in testing conditions. ISO 10993-4 describes hemocompatibility tests in five different categories (thrombosis, coagulation, platelets, hematology, and immunology). Here we put together the tests that ISO 10993 and/or American Society for Testing and Materials (ASTM) suggest to evaluate hemocompatibility and we emphases on their utility for magnetic nanoparticules testing. The individual tests are not discussed in detail; they may be performed either in vivo or, preferably, in vitro. For each test we made few considerations with criticism. There is still some uncertainty with respect to what is actually required by the regulatory authorities for the hemocompatibility test, and there is still no harmony between ASTM and ISO 10993 regulations regarding some aspects to be standardised.     

Desmoplastic small round cell tumor in children: a new therapeutic approach

Purpose

Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histologic and immunohistochemical features occurring in a young population with a male predominance. The tumor appears to arise as masses in the abdominal cavity without a clear visceral origin. Five patients with DSRCT were treated as usual with combined chemoradiation and surgery. In addition, in our center, patients underwent autologous bone marrow transplant (BMT), which is a novel approach to this disease.

Methods

Charts of 5 patients (4 males, mean age of 11 years) treated between 2000 and 2007 were reviewed. The diagnosis of DSRCT was made on the basis of clinical examination, computed tomographic scan, and explorative laparotomy with biopsy, and biochemical markers were negative. All patients were treated with aggressive chemoradiation and surgery. Three patients also had autologous BMT.

Results

Three patients (BMT recipients) responded to treatment. The responding patients had surgery with the intent of removing all disease. Two patients died of their cancer, neither of whom underwent BMT.

Conclusion

The patients DSRCT are sensitive to an aggressive combination of chemotherapy, surgical debulking, and radiation therapy, followed by autologous BMT. It appears that this new multifaceted treatment offers good palliation, which may prolong survival and a possible cure.     

Prostatic diseases under focus in a university hospital in Eastern Saudi Arabia: A 15-year experience

Objectives:

To explore the spectrum of pathologies diagnosed in prostatic biopsies of Saudi men, and test whether the frequency of diagnosing the malignant fraction has been changed over the last 15 years, and assess the association between chronic inflammation (CI) with both benign prostatic hyperplasia (BPH) and cancer (PCa), and investigate the histological findings of cases presented with acute urinary retention (AUR) clinically.

Methods:

This is a retrospective cohort study including all prostatic biopsies accessed in the files in the Surgical Pathology Laboratory of King Fahd University Hospital, Alkhobar, Kingdom of Saudi Arabia over 15 years (1999-2013) for Saudi men. Age, procedure indication, and final diagnoses were retrieved and slides were reviewed.

Results:

There were 360 cases included in this study with a median age of 65 year-old. The BPH comprised the most (64.7%), while PCa accounted for 89 cases, 13.5% of which were incidental. Most cases of both BPH and PCa were diagnosed in the seventh decade. The frequency of diagnosing PCa did not show a solid rise or fall over time. Chronic inflammation is more related to BPH than to PCa. Only CI showed a significant statistical association with AUR.

Conclusion:

Prostatic diseases show a stable trend over time. While CI is a common dominator for both BPH and PCa, it is associated more with BPH. Among all histological findings, only CI is related to the clinical presentation of AUR.The spectrum of prostatic diseases is a common health concern all over the world. While benign prostatic hyperplasia (BPH) is the most frequent urologic diagnosis in elderly males worldwide, affecting approximately one third of males in their 60’s,1,2 prostatic carcinoma (PCa) is the second most common cause of cancer-related death in males after lung cancer.3 The disease represents clear racial and national differences, with its highest incidence in blacks in the West, and lowest in Asian males.4 Recently, there has been a rising trend for PCa in populations that are thought to be of low risk.5 Furthermore, the relationship between chronic inflammation (CI) and presence and progression of both BPH and PCa is controversial.6-9 On the other hand, acute urinary retention (AUR), which is the most frequent emergency in urology, is mostly developed in a background of BPH.10 Whether other pathologies, such as CI and infarction increase the risk of this complication is debated.11-13 In this work, we retrospectively reviewed the whole spectrum of prostatic pathologies diagnosed in our center during the last 15 years, including prostatic intraepithelial neoplasia (PIN) and atypical small acinar proliferation (ASAP), and study various diseases in relation to age of diagnosis, explore the change in trend of diagnosing PCa over a period witness an increase in screening and gradual westernization of lifestyle, test the relationship between CI and both BPH and PCa, and also, we investigate the role of different biopsy findings in relation to the clinical presentation with AUR.     

Six-month clinical outcome of cyclosporine microemulsion formulation (Sigmasporin Microral) in stable renal transplant patients previously maintained on sandimmun neoral

The trial objective was to investigate the feasibility and safety of conversion to a generic microemulsion cyclosporine in stable renal transplant patients premaintained on Neoral. We enrolled 75 patients from seven centers in five Middle Eastern countries monitored them for 6 months after conversion to Sigmasporin Microral. Readings at 0, 0.5, 1, 2, 3, 4.5, and 6 months included cyclosporine blood level, serum creatinine, liver enzymes, lipid profile, blood sugar, blood pressure and adverse events. Patients included 54 men and 21 women of mean age 38.9 +/- 10.7 years at 30.3 +/- 29.3 months post-transplantation maintained on Sigmasporin Microral dose of 2.8 +/- 1.0 mg/kg per day; they were observed to be stable throughout the study period as reflected by the therapeutic blood C(0) level of 181.6 +/- 102.1 and C(2) of 759.2 +/- 384.4. Their absorption profile as represented by C(2)/C(0) was 4.9 +/- 2.8, and C(2)/cyclosporine dose of 282.3 +/- 128.8. An average serum creatinine level of 116.1 +/- 29.5 mumol/L denoted stable graft function and their liver enzymes did not change during the study. No new-onset cases of hypertension, diabetes mellitus, or hyperlipidemia were reported among the patients. Graft function was stable for all patients, except for two incidences of mild acute rejection and two of mild cyclosporine nephrotoxicity; graft and patient survival rates were both 100%. Results of this 6-month study showed that Sigmasporin Microral was effective to maintain stable renal function in kidney transplant patients converted from Neoral with similar safety and tolerability profiles as those reported in the literature.     

HP26PSEUDO‐ACHALASIA FOLLOWING A SLIPPED LAPAROSCOPICALLY PLACED ADJUSTABLE GASTRIC BAND: A CASE REPORT

Purpose To demonstrate that laparoscopic adjustable gastric banding may promote oesophageal dilatation or interfere with oesophageal motility. Methodology We report a case of a 67 year old female with a complex medical history who developed secondary achalasia from a slipped laparoscopic adjustable gastric band for weight loss. This led to recurring episodes of aspiration pneumonia requiring multiple admissions at North Shore Hospital, Auckland, New Zealand. Results A decision was made to remove the gastric band, five years after its initial insertion. At one month follow up, she was swallowing normally and oesophageal manometry had returned to normal. Conclusion Oesophageal dysmotility is sometimes seen in patients who have bands that are adjusted too tightly or in whom the band has slipped. This can lead to serious complications if unrecognized and incorrectly treated. Oesophageal symptoms in patients with adjustable bands must be considered secondary to the band until proven otherwise ie removal of the band or complete deflation.     

Disappearance of Tophi in Familial Juvenile Hyperuricemic Nephropathy after Kidney Transplantation

A 40-year-old man who had been on hemodialysis for 25 months due to familial juvenile hyperuricemic nephropathy (FJHN) received a kidney transplant. Biopsy of his native kidney had shown tubulo-interstitial nephropathy. Genetic analysis confirmed abnormal uromodulin expression due to a mutation in the exon 4 of the UMOD gene. He had multiple tophi on the day of transplantation, including some on his fingers. He received immunosuppressive treatment including polyclonal antilymphocyte antibodies, mycophenolate mofetil, steroids and cyclosporine and achieved excellent renal function, with serum creatinine at 13 mg/L on day 10 posttransplantation and 9.4 mg/L at 6 months. His uric acid excretion rate increased from 4.4% at day 2 posttransplantation to 7.7% 6 months after transplantation. The number and sizes of the tophi were reduced 3 months posttransplantation, and nearly disappeared at month 6. Serum uric acid level decreased slowly from 650 mumol/L before transplantation to 300 mumol/L. Reduction of tophi was probably due to the absence of the mutated UMOD gene in the transplanted kidney.