Treatment of and mortality from diabetic renal failure in patients identified in the 1985 United Kingdom survey. Joint Working Party on Diabetic Renal Failure of the British Diabetic Association,Renal Association,and the Research Unit of the Royal College of Physicians.

The aim of the study was to determine the outcome in 181 diabetic patients with advanced, previously untreated renal impairment who had been identified in a survey conducted in six health regions in the United Kingdom in 1985. Late in 1987 questionnaires were sent to the consultant physicians, geriatricians, and nephrologists who had reported on the 181 patients, asking whether the patient had started receiving dialysis, had received a transplant, or had died. In all, 176 of the patients were traced, 164 having either died or received renal support treatment by the end of 1986. Nearly two thirds (107) of the patients received renal support treatment, which was renal transplantation in five and dialysis in 102. This is an increase on previous years. A third of the patients (57) died without having received renal support treatment. In 15 patients death was unavoidable and mainly from acute myocardial infarction (10 patients), but 28 patients (half of those who died untreated) died from renal failure, sometimes with fluid retention that was ascribed to heart failure (18 patients). Most of the patients would have benefited from renal support treatment. This neglect should no longer occur.     

Failure of sequential therapy to eradicate Helicobacter pylori in previously treated subjects

BACKGROUND: Recently, studies in adults and subsequently in children have demonstrated a very high success rate for sequential therapy as a primary therapy when compared to traditional therapy regimens. METHODs: We report our experience with a sequential therapy regimen for the eradication of Helicobacter pylori in five infected children and a young adult, whose conventional therapy regimens had been unsuccessful. RESULTS: Five patients failed the sequential therapy. All of them experienced between two and four failures of traditional therapy prior to the sequential treatment protocol. The only patient who succeeded on the sequential therapy had just one previous failure. All of our patients who had failed sequential therapy achieved eradication of the bacteria with quadruple therapy. CONCLUSIONS: In view of our disappointing results, sequential therapy is unsuccessful as a therapy for children and young adults who have failed previous treatment regimens. At the present time, quadruple therapy is indicated for this group. Well-designed placebo-controlled trials are indicated to further characterize this group of patients.     

Effect of hyperthermia and chemotherapeutic agents on TRAIL-induced cell death in human colon cancer cells

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent because of its tumor selectivity. TRAIL is known to induce apoptosis in cancer cells but spare most normal cells. In the previous study [Yoo and Lee, 2007], we have reported that hyperthermia could enhance the cytotoxicity of TRAIL-induced apoptosis. We observed in human colorectal cancer cell line CX-1 that TRAIL-induced apoptotic death and also that mild hyperthermia promoted TRAIL-induced apoptotic death through caspase activation and cytochrome-c release. Although its effects in vivo are not clear, hyperthermia has been used as an adjunctive therapy for cancer. Hyperthermia is often accompanied by chemotherapy to enhance its effect. In this study, CX-1 colorectal adenocarcinoma cells were treated with TRAIL concurrently with hyperthermia and oxaliplatin or melphalan. To evaluate the cell death effects on tumor cells via hyperthermia and TRAIL and chemotherapeutic agents, FACS analysis, DNA fragmentation, and immunoblottings for PARP-1 and several caspases and antiapoptotic proteins were performed. Activities of casapse-8, caspase-9, and caspase-3 were also measured in hyperthermic condition. Interestingly, when analyzed with Western blot, we detected little change in the intracellular levels of proteins related to apoptosis. Clonogenic assay shows, however, that chemotherapeutic agents will trigger cancer cell death, either apoptotic or non-apoptotic, more efficiently. We demonstrate here that CX-1 cells exposed to 42 degrees C and chemotherapeutic agents were sensitized and died by apoptotic and non-apoptotic cell death even in low concentration (10 ng/ml) of TRAIL.     

The fate of free flaps used to reconstruct defects in recurrent head and neck cancers

The purpose of this study was to assess free-flap viability in patients treated for recurrent head and neck cancers. A 10-year retrospective review identified 121 patients who had had prior head and neck cancers extirpated for cure, who subsequently presented with documented recurrent cancers that were removed, and who then underwent reconstruction with free flaps. The charts of these patients were reviewed for patient demographics, tumor types, location, flaps used for reconstruction, size of area requiring reconstruction, length of operation, previous radiation, and all postoperative morbidity and mortality. The time to recurrence ranged from 21/2 months to 21 years. The majority of tumors treated were squamous cell carcinomas (n = 82). Most of them were located intraorally (n = 75). Radiation therapy had been delivered to 88 patients before their free-flap reconstructions. In this series, 31 percent of all patients required additional surgery for complications, 14 percent of free flaps were lost, and 4 percent of patients died within 30 days of their operation. The significant findings were that a flap that was >4 cm in diameter was related to flap loss (p = 0.03 by the chi2 method) and that flap loss was related to operative times greater than 11 hours (p = 0.03 by the chi2 method). It was concluded that recurrent head and neck cancers with large postextirpation defects that required prolonged operative times yielded a significantly high tendency toward flap failure.     

Secondary Respiratory Infection in Hospital Patients: Effect of Antimicrobial Agents and Environment

A prospective study of 358 medical and 234 postoperative patients with clinical evidence of secondary chest infection showed that previous administration of antimicrobial agents greatly reduced the chance of obtaining a clear-cut laboratory report. In patients with radiographical evidence of pneumonia this led to a fourfold decrease in the overall rate of isolation of potential pathogens. Furthermore, 81 diverse “coliforms” were isolated from 258 medical and surgical patients who had received previous antimicrobial therapy while only four coliforms (all Escherichia coli) were isolated from 334 untreated patients. Thus the general hospital environment on its own seemed to have a negligible influence in promoting the growth of coliform flora in sputum. Any unique effect of underlying disease in this regard was masked by that of previous therapy. Finally, the results raised the possibility that previous antimicrobial therapy might have increased the risk of secondary pneumonia in hospital patients.     

Esophageal cytology in patients receiving cytotoxic drug therapy

Our experience with the cytology of esophageal brush specimens from patients who did not have either gastric or esophageal cancer but who received a variety of chemotherapeutic agents is reported. Ten patients received chemotherapy alone, and nine received combined chemotherapy and radiation therapy. Of the ten patients, three showed evidence of moderate to severe epithelial atypia, which was not seen in the combined treatment group or the control group. The cytologic atypias in the three patients consisted of variation in nuclear size with crowding and overlapping, an increased nuclear-cytoplasmic ratio and multiple nucleoli, many of which varied in size and shape. There was also evidence of cell death and keratinization. Although these patients had not been irradiated, other striking changes were similar to those seen following radiation therapy. The cytologic changes reported here pose a serious diagnostic problem because they may be so severe as to mimic malignant transformation. Evidence of infection by herpes simplex alone or herpes simplex associated with Candida was seen in 32% of the treated patients and in 4% of the control group.     

No evidence for prolonged excretion of polioviruses in persons with residual paralytic poliomyelitis in Ethiopia, Pakistan and Guatemala.

Persons who have developed acute flaccid paralysis following infection with wild-type polioviruses or vaccine-associated paralytic poliomyelitis usually excrete polioviruses for only a few weeks. However, some patients with paralytic poliomyelitis have had prolonged excretion of polioviruses for periods of up to 10 years after onset of disease. Most prolonged excretors have been identified in industrialized countries. We studied 348 patients 2-28 years old in Ethiopia, Pakistan and Guatemala with residual paralytic poliomyelitis to determine if they had IgA or IgG deficiency or persistent poliomyelitis excretion at least 1 year after onset of disease. None of the 348 affected individuals had IgG deficiency or persistent poliovirus excretion. One child had borderline low serum IgA concentration. Since we did not study children under 2 years of age, persons born with IgG deficiency disorders may have died in developing countries where replacement immunoglobulin therapy is not readily available. Nevertheless, persistent poliovirus excretion among persons 2 years of age and older with residual paralytic poliomyelitis is uncommon in developing countries.     

Colony stimulating factor levels in human serum and urine following chemotherapy.

The colony stimulating activity (CSA) of serum and urine specimens from 10 patients with lymphomas before and after treatment with standard multidrug chemotherapeutic regimens has been studied. Prominent rises in the CSA in the urine of eight of these 10 patients correlating temporally with initiation of therapy was demonstrated when compared to pretreatment control values. Hourly serum specimens were collected following the administration of intravenous chemotherapeutic agents in two of these patients. In one of these two patients there was a prominent and early rise in CSA which returned to control values by the 12th hr after intravenous drug administration. In two patients who developed little or no increase in CSA during therapy, urine specimens were studied for the presence of inhibitors to colony stimulating factor. Aliquots of urine from each of these two patients when mixed with a standard control urine of known CSA, produced marked inhibition.     

Childhood deaths from intussusception in England and Wales, 1984-9.

OBJECTIVE--To assess the incidence of potentially avoidable factors contributing to death of children with intussusception. DESIGN--Review of children who died with intussusception in England and Wales between 1984 and 1989 from data of the Office of Population Censuses and Surveys, case notes, coroners'' records, and necropsy reports. MAIN OUTCOME MEASURES--Unambiguous objective criteria such as failure to diagnose intussusception within 24 hours of admission. RESULTS--33 children died of acute intussusception in England and Wales between 1984 and 1989 compared with 67 in the previous six years. Their median age was 7 months (range 2 months to 12 years), and two thirds were boys. Half of the deaths occurred at home or soon after arrival at hospital but 15 patients had surgery. Potentially avoidable factors contributing to death were identified in 20 (61%) children, all but three of whom had ileocolic intussusception. These factors were excessive delay in diagnosis, inadequate intravenous fluid and antibiotic therapy, delay in recognising recurrent or residual intussusception after hydrostatic reduction, and surgical complications. Of the 13 patients in whom no avoidable factors were identified, there were nine of 11 children with isolated small bowel intussusception, who tended to have atypical presentations. CONCLUSION--Although the mortality from intussusception has declined, there remains ample opportunity for improved management.     

131I]metaiodobenzylguanidine and high-dose chemotherapy with bone marrow rescue in advanced neuroblastoma.

High-dose chemotherapy (HDT) and autologous bone marrow rescue (ABMR) is routinely used as consolidation treatment in advanced neuroblastoma. This study is presently examining the efficacy and toxicity of combined [131I]metaiodobenzylguanidine (131I-MIBG) therapy with HDT and ABMR. Five children (4 male, 1 female), median age of 8 years (range 4-11 years) were treated, 3 at relapse and 2 after initial chemotherapy. A single infusion of 131I-MIBG (median activity 11.1 GBq, range 7.4-11.2 GBq) was followed by HDT and ABMR 14-32 days later. High-dose chemotherapy consisted of carboplatin and melphalan in 4 patients, and vincristine, etoposide, carboplatin and melphalan in 1. One patient developed a septicaemia and died, and another failed to engraft; both had extensive bone marrow infiltration at the time of 131I-MIBG therapy. The combined therapy was well tolerated by the three other patients. Two children have relapsed and died (including one who failed to engraft), and 2 are alive 17 and 41 months after ABMR. In the absence of extensive bone marrow metastases, combined therapy offers potential as a means of consolidating treatment in advanced neuroblastoma.     

Influence of war circumstances on tumor morphological characteristics in patients with breast cancer

The influence of war circumstances on tumor morphological characteristics in patients with breast cancer has not been studied up to now. The aim of this study is to investigate if war circumstances have influenced breast cancer incidence. The study covered both the patients in which during a period of observation a breast cancer was diagnosed as well as those who died of the same disease in the same period. Three sources of data were used: 1) The archives of the Oncology and Radiotherapy Center of the University Hospital "Split" (UHS): hospital data of 768 patients were reviewed. The war sample consisted of 380 patients aged 59.4+/-12.1 (31 to 86) (including 5 males), whereas the pre-war sample was made up of 388 patients aged 58.4+/-12.7 (19 to 88) (including 3 males); 2) Register of death of the Pathology Department of UHS with 162 analyzed persons whose death was caused by breast cancer in the six-year period between 1988 and 1993. The list of 162 dead patients included 79 people who died from breast cancer diagnosed in that period (1988-1993) and another 83 people that had been diagnosed before that period; 3) The biopsy register of the Pathology Department of UHS with 851 breast biopsies performed between 1988 and 1993. Breast cancer is predominantly a female illness (99.1%). The war circumstances influenced the of T, N and M rate. The rate of N2, N3, Ml were conspicuously higher in the war period. There were significantly more malignant histological diagnoses found in new patients and also significantly more patients died due to breast cancer. Stress and other war circumstances undoubtedly have a negative impact on the numerous markers of breast cancer which we have proved in this study.     

Factors associated with suicide after parasuicide in young people.

OBJECTIVE--To determine factors associated with completed suicide in young parasuicide patients. DESIGN--Case-control study. SETTING--Regional poisoning treatment centre in a teaching general hospital. SUBJECTS--Patients who, between 1968 and 1985 when aged 15-24 years, were admitted to the regional poisoning treatment centre because of deliberate self poisoning or self injury. Cases (n = 62) consisted of those who by the end of 1985 had died locally from either suicide (n = 41) or possible suicide (n = 21). Controls (n = 124) were patients who were known not to have died locally during the study period. Two controls were selected for each case, matched by sex, age (within two years), and length of follow up. MAIN OUTCOME MEASURES--Possible predictors of completed suicide. RESULTS--Univariate analysis (conditional logistic regression) showed that risk of death due to suicide and possible suicide was associated with six factors: social class V (odds ratio 2.7, 95% confidence interval 1.1 to 6.7), unemployment (2.8, 1.4 to 5.8), previous inpatient psychiatric treatment (4.9, 2.2 to 10.9), substance misuse (3.3, 1.6 to 6.8), personality disorder (2.1, 1.03 to 4.4), and previous attempted suicide (2.3, 1.2 to 4.4). Multivariate analysis identified two factors as significantly contributing to the model that best discriminated between the cases and controls: substance misuse (alcohol or drugs, or both) (adjusted odds ratio 3.9) and previous inpatient psychiatric treatment (3.7). These factors seemed to be associated with suicide after attempted suicide in both the short term (less than 12 months) and the long term (one year or more) and were also identified when the analysis was restricted to subjects who definitely died by suicide and their controls. CONCLUSIONS--Suicide after parasuicide in young people is associated with substance misuse. This suggests that prevention of suicide in young people who attempt suicide might be improved by close liaison between general hospital services for patients who have attempted suicide and services for young substance misusers and by measures aimed at preventing substance misuse in young people.     

The Real Importance of Pre-Existing Comorbidities on Long-Term Mortality after Acute Kidney Injury

Background

The causes of death on long-term mortality after acute kidney injury (AKI) have not been well studied. The purpose of the study was to evaluate the role of comorbidities and the causes of death on the long-term mortality after AKI.

Methodology/Principal Findings

We retrospectively studied 507 patients who experienced AKI in 2005–2006 and were discharged free from dialysis. In June 2008 (median: 21 months after AKI), we found that 193 (38%) patients had died. This mortality is much higher than the mortality of the population of São Paulo City, even after adjustment for age. A multiple survival analysis was performed using Cox proportional hazards regression model and showed that death was associated with Khan’s index indicating high risk [adjusted hazard ratio 2.54 (1.38–4.66)], chronic liver disease [1.93 (1.15–3.22)], admission to non-surgical ward [1.85 (1.30–2.61)] and a second AKI episode during the same hospitalization [1.74 (1.12–2.71)]. The AKI severity evaluated either by the worst stage reached during AKI (P = 0.20) or by the need for dialysis (P = 0.12) was not associated with death. The causes of death were identified by a death certificate in 85% of the non-survivors. Among those who died from circulatory system diseases (the main cause of death), 59% had already suffered from hypertension, 34% from diabetes, 47% from heart failure, 38% from coronary disease, and 66% had a glomerular filtration rate <60 previous to the AKI episode. Among those who died from neoplasms, 79% already had the disease previously.

Conclusions

Among AKI survivors who were discharged free from dialysis the increased long-term mortality was associated with their pre-existing chronic conditions and not with the severity of the AKI episode. These findings suggest that these survivors should have a medical follow-up after hospital discharge and that all efforts should be made to control their comorbidities.     

Association of single nucleotide polymorphisms in SOD2, XRCC1 and XRCC3 with susceptibility for the development of adverse effects resulting from radiotherapy for prostate cancer

The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam radiotherapy, with or without hormone therapy, were genotyped for SNPs in SOD2, XRCC1 and XRCC3. Three common late tissue toxicities were investigated: late rectal bleeding, urinary morbidity, and erectile dysfunction. Patients with the XRCC1 rs25489 G/A (Arg280His) genotype were more likely to develop erectile dysfunction after irradiation than patients who had the G/G genotype (67% compared to 24%; P=0.048). In addition, patients who had the SOD2 rs4880 T/C (Val16Ala) genotype exhibited a significant increase in grade 2 late rectal bleeding compared to patients who had either the C/C or T/T genotype for this SNP (8% compared to 0%; P=0.02). Finally, patients with the combination of the SOD2 rs4880 C/T genotype and XRCC3 rs861539 T/C (Thr241Met) genotype experienced a significant increase in grade 2 late rectal bleeding compared to patients without this particular genotypic arrangement (14% compared to 1%; P=0.002). These results suggest that SNPs in the SOD2, XRCC1 and XRCC3 genes are associated with the development of late radiation injury in patients treated with radiation therapy for prostate adenocarcinoma.     

Posaconazole Salvage Treatment for Invasive Fungal Infection

Invasive fungal infection (IFI) is an important cause of morbidity and mortality. Posaconazole is a second generation triazole with a broad spectrum, and it may be suitable for salvage antifungal treatment although posaconazole is not usually considered to be as first-line antifungal therapy for IFI. The purpose of this study was to assess the utility of posaconazole salvage treatment for IFI. We conducted a retrospective review of patients with salvage antifungal treatment with posaconazole for IFI at our institution between December 2007 and July 2012. A total of ten patients received posaconazole salvage IFI. Etiology of IFI was consisting of mucormycosis (four patients), Paecilomyces variotii (one patient), and unspecified IFI etiology (five patients). Causes of posaconazole treatment were following; intolerance of previous antifungal therapy in five patients, refractory IFI on previous antifungal therapy in four patients, and both intolerance of previous antifungal therapy and refractory IFI on previous antifungal therapy in one patient. Duration of posaconazole salvage treatment ranged from 15 to 355 days with median 47 days. The overall successful posaconazole salvage treatment response rate was 80.0 % (8 of 10 patients). There were three patients who died during the study period. However, only one death was attributed to the progression of IFI. Two patients discontinued posaconazole due to adverse events. Posaconazole salvage treatment was effective antifungal therapy for IFI. Further studies are needed to define the optimal therapeutic strategy.     

Factors determining prognosis in streptococcal toxic shock-like syndrome: results of a nationwide investigation in Japan

Since the first report of streptococcal toxic shock-like syndrome (TSLS) in Japan, the numbers of reported patients have been increasing. However, clinical manifestations remain somewhat unclear, and factors potentially defining prognosis remain to be identified. We conducted a retrospective nationwide postal survey of major Japanese hospitals concerning clinical manifestations of invasive streptococcal infections including necrotizing fasciitis and TSLS. We evaluated 30 patients who died and 36 survivors. The overall mortality rate was 45%. Physical and laboratory findings on admission were compared statistically between fatal cases and surviving patients. Most laboratory results from the patients who died showed greater abnormality than results from the survivors. Patients who died had significantly fewer leukocytes and platelets, although their C-reactive protein concentrations were similar to those in survivors. Creatinine was significantly higher, and temperature and blood pressure were significantly lower, in patients who died. Patients with invasive streptococcal infections should be managed aggressively when the above features are present.     

Epidemiology and Course of Gastrointestinal Haemorrhage in North-east Scotland

A prospective study was made of 817 consecutive episodes of major gastrointestinal haemorrhage in patients admitted to hospital during 1967-8 from the defined population of North-East Scotland. The yearly admission rate was 116 per 100,000 population. Comparison of the data for city and country residents showed no appreciable differences. In the duodenal ulcer group there was an undue incidence of bleeding among foremen and skilled workers and among those who were unmarried or widowed.Both the clinical history and the results of any previous barium meal examinations were unreliable guides to the source of the current haemorrhage. Prognosis was worse for patients who did not have a dyspeptic history and was better for those who had bled on a previous occasion. The simultaneous ingestion of alcohol and aspirin had an adverse effect on the occurrence of bleeding. Forty-seven per cent. of the patients had another major coincidental disease.Mortality was 13·7% in the whole series and 8·6% in those with peptic ulcer (duodenal ulcer 7·1%, gastric ulcer 16·9%). In 28% of the patients further haemorrhage occurred after admission to hospital and caused a 28·8% mortality. Seventy-four patients were already in hospital when they first bled and 44% of them died.     

Non-heart-beating organ donors as a source of kidneys for transplantation: a chart review

BACKGROUND: Organ transplantation is the treatment of choice for patients with end-stage organ failure, but the supply of organs has not increased to meet demand. This study was undertaken to determine the potential for kidney donation from patients with irremediable brain injuries who do not meet the criteria for brain death and who experience cardiopulmonary arrest after withdrawal of ventilatory support (controlled non-heart-beating organ donors). METHODS: The charts of 209 patients who died during 1995 in the Emergency Department and the intensive care unit at the Foothills Hospital in Calgary were reviewed. The records of patients who met the criteria for controlled non-heart-beating organ donation were studied in detail. The main outcome measure was the time from discontinuation of ventilation until cardiopulmonary arrest. RESULTS: Seventeen potential controlled non-heart-beating organ donors were identified. Their mean age was 62 (standard deviation 19) years. Twelve of the patients (71%) had had a cerebrovascular accident, and more than half (10 [59%]) did not meet the criteria for brain death because one or more brain stem reflexes were present. At the time of withdrawal of ventilatory support, the mean serum creatinine level was 71 (29) mumol/L, mean urine output was 214 (178) mL/h, and 9 (53%) patients were receiving inotropic agents. The mean time from withdrawal of ventilatory support to cardiac arrest was 2.3 (5.0) hours; 13 of the 17 patients died within 1 hour, and all but one died within 6 hours. For the year for which charts were reviewed, 33 potential conventional donors (people whose hearts were beating) were identified, of whom 21 (64%) became donors. On the assumption that 40% of the potential controlled non-heart-beating donors would not in fact have been donors (25% because of family refusal and 15% because of nonviability of the organs), there might have been 10 additional donors, which would have increased the supply of cadaveric kidneys for transplantation by 48%. INTERPRETATION: A significant number of viable kidneys could be retrieved and transplanted if eligibility for kidney donation was extended to include controlled non-heart-beating organ donors.     

Hypertrophic cardiomyopathy and sudden cardiac death due to physical exercise in Croatia in a 27-year period

The paper deals with the sudden cardiac death during physical exercise in males in Croatia. The data are a part of a retrospective study dealing with 69 sudden death due to physical activity in men in Croatia during 27 years: from January 1, 1984 to December 31, 2010. Three of them suddenly died during training and two of them died during recreational physical exercise, probably because of malignant ventricular arrhythmia due to hyperthrophic cardiomyopathy. One had an obstructive form of hypertrophic cardiomyopathy with i.v. septum of 40 mm and four had a non-obstructive forms of hyperthrophic cardiomyopathy with left ventricular wall of 18-20-22-25 mm. First athlete was a short trails runner, aged 24, with no any previous physical discomforts, who suddenly collapsed and died during training. The second athlete was a soccer player aged 18, with no any previous physical discomfort, who suddenly collapsed and died during training. The third aged 15, was a school boy, basketball player, with no any previous physical discomfort, who collapsed and died during training. Two aged 25 and 34, were with no physical discomfort during exercise and died suddenly during recreational soccer games. A sudden cardiac death due to physical exercise in young athletes in Croatia suffered of hyperthropic cardiomyopathy reached 0.06/100 000 yearly (p = 0.00000) in 27 years, in teenagers 0.26/100 000 (p = 0.00226), in teenagers suffered of hypertrophic cardiomyopathy reached 0.10/100 000 (p = 0.00000), in all young athletes suffered of other heart diseases reached 0.19/100 000 (p = 0.00005), and in the total male population aged 15 or more, engaged in sports and recreational physical exercise: 0.71/100.0000 (p = 0.00001).