Influence of face mask design on bag-valve-mask ventilation performance: a randomized simulation study.

BACKGROUND: Different face mask designs can influence bag-valve-mask (BVM) ventilation performance during resuscitation. We compared a single-use, air-cushioned face mask (AM) with a reusable silicone face mask (SM) for quality of BVM ventilation on a manikin simulating cardiac arrest. METHODS: Thirty-two physicians were recruited, and a prospective, randomized, crossover observational study was conducted after an American Heart Association-accredited basic life support provider course and standardized practice time were completed. Participants performed 12 cycles of BVM ventilation with both the AM and SM on a SmartMan lung simulator. RESULTS: Mean tidal volume was significantly higher in ventilations performed using the AM vs. the SM (548 ± 159 ml vs. 439 ± 163 ml, P < 0.01). In addition, the proportion of low-volume ventilation was significantly lower with the AM than the SM [6/12 (2-11) vs. 9/12 (5-12), P = 0.03]. Bag-valve-AM ventilation volume was not affected by the physical characteristics of the rescuers, except for sex. In contrast, bag-valve-SM ventilation volume was affected by most of the characteristics tested, including sex, height, weight, hand width, hand length, and grip power. CONCLUSION: The AM seems to be a more efficient face mask than the SM at delivering sufficient ventilation volumes. The performance of the AM did not seem to be associated with the physical characteristics of the rescuers, whereas that of the SM was affected by these factors. The SM may not be an appropriate face mask for performing one-person BVM ventilation during resuscitation for rescuers who are smaller in stature, have a smaller hand size, or have weaker grip power.

Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B.

BACKGROUND: Metabolic syndrome is associated with non-alcoholic steatohepatitis and cryptogenic cirrhosis. Whether metabolic syndrome affects the severity of chronic hepatitis B (CHB) is unclear. AIM: We aimed to study the relationship between metabolic syndrome and the risk of liver cirrhosis in patients with CHB. METHODS: We prospectively recruited patients with CHB from primary care and hospital clinics for liver stiffness measurement (LSM) with transient elastography to diagnose early cirrhosis. Probable cirrhosis was defined as LSM >or=13.4 kPa. We analysed a subgroup of patients with paired LSM and liver biopsies to validate the accuracy of LSM. RESULTS: 1466 patients had reliable LSM and 134 (9%) patients had adequate liver biopsy. 188 (13%) patients had metabolic syndrome. Histological liver cirrhosis was present in 32/134 (24%) patients. Histological liver cirrhosis was more common among patients who had metabolic syndrome (38%) versus those who did not (11%, p<0.001). The specificity of probable cirrhosis on LSM for histological cirrhosis was 94%. Probable cirrhosis was present in 187 (13%) patients. Metabolic syndrome was more prevalent in patients with probable cirrhosis (24%) than those without cirrhosis (11%, p<0.001). After adjustment for anthropometric, biochemical and virological factors, metabolic syndrome remained an independent factor associated with probable cirrhosis (odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.6). The odds ratios of probable cirrhosis were 1.4 (95% CI, 0.9 to 2.3), 2.6 (95% CI, 1.7 to 4.3), 4.1 (95% CI, 2.4 to 7.1), 4.0 (95% CI, 1.9 to 8.4) and 5.5 (95% CI, 1.8 to 16.7) in patients with one, two, three, four and five components of metabolic syndrome, respectively. CONCLUSION: Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB.

Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B.

The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.

Spontaneous regression of primary cutaneous Epstein-Barr virus-positive, CD30-positive anaplastic large T-cell lymphoma in a heart-transplant recipient.

We presented a rare case of primary cutaneous Epstein-Barr virus-positive, CD30-positive anasplastic large cell lymphoma in a 64-year-old man who had received a heart transplant 11 years previously. The first presenting symptom was the appearance of erythematous skin nodules on the right leg. The lesions subsided with dose reduction of immunosuppressant alone. There was no recurrence 9 months after the first diagnosis. We propose that dose reduction of immunosuppressant alone may be an effective treatment for localized, indolent, post-transplant-related primary cutaneous lymphoma. Our case shows the importance of regular surveillance of skin cancer in patients who have received organ transplant.

Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease.

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have gut dysbiosis and intestinal bacterial overgrowth. AIM: To test the hypothesis that endotoxemia is associated with the histological severity of nonalcoholic fatty liver disease (NAFLD) and determine factors associated with endotoxemia. METHODS: The endotoxemia markers lipopolysaccharide-binding protein (LBP) and endotoxin levels were measured in 237 NAFLD patients 1 day before liver biopsy. Biomarkers of liver injury and transient elastography were performed as additional markers of disease severity. RESULTS: A total of 114/237 (48%) patients had NASH and 80/237 (34%) had F2-4 fibrosis. LBP was correlated with lobular inflammation (P=.001), while both LBP (P=.0004) and endotoxin levels (P=0.008) were correlated with fibrosis. LBP was also correlated with cytokeratin-18 fragments (P=.002) and aspartate aminotransferase-to-alanine aminotransferase ratio (P=.006), and both LBP (P=.019) and endotoxin (P=.006) were correlated with liver stiffness measurement by transient elastography. LBP was increased in patients with NASH (15.3±4.6 vs 13.8±3.3 µg/mL; P=.005) and F2-4 fibrosis (15.4±4.4 vs 14.0±3.7 µg/mL; P=.008). Interestingly, patients harbouring the TM6SF2 rs58542926 T allele that predispose to NAFLD/NASH had higher LBP level. By multivariate analysis, gender, higher body mass index and glycated haemoglobin, and TM6SF2 variants were independent factors associated with increased LBP level. CONCLUSIONS: Endotoxemia is positively associated with NASH and significant fibrosis. The association between TM6SF2 and endotoxemia warrants further investigations. The findings may shed light on the pathogenesis of NASH and inform a novel treatment target.

The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria.

PURPOSE: To determine the natural history of immunoglobulin (Ig) A nephropathy among patients who presented with hematuria and minimal proteinuria, and factors associated with the development of adverse clinical events, such as proteinuria. SUBJECTS AND METHODS: In Hong Kong, all patients who present with isolated hematuria are referred for renal biopsy after urologic diseases are ruled out. We reviewed the clinical course of 72 consecutive patients with histologically confirmed IgA nephropathy who presented with hematuria and minimal proteinuria (0.4 g/day or less). All patients were normotensive and had normal renal function at presentation. Adverse events were defined as proteinuria greater than 1 g per day, hypertension, or impaired renal function (serum creatinine level 120 micromol/L or estimated creatinine clearance < 70 mL per minute). RESULTS: The mean (+/- SD) age at presentation was 27 +/- 8 years; 56 (78%) were female. Nine patients (13%) had grade 2 histologic lesions. During a median follow-up of 7 years, 32 patients (44%) developed adverse events: 24 (33%) developed proteinuria of 1 g per day or more, 19 (26%) became hypertensive, and 5 (7%) developed impaired renal function. Another 30 patients (42%) had persistently abnormal urinalysis examinations. Only 10 patients (14%) had complete resolution of hematuria. The median time for progression from proteinuria (> l g/day) to renal impairment was 84 months (range 56 to 132). In a multivariate analysis, age at presentation (relative risk [RR] per 10 years of age = 2.0; 95% confidence interval [CI], 1.2 to 3.4) and histologic grade (grade 2 versus grade 1, RR = 4.5; 95% CI, 1.7 to 12) were independent predictors of developing an adverse event. CONCLUSIONS: IgA nephropathy that presents with hematuria and minimal proteinuria is usually a progressive disease. Life-long follow-up with regular monitoring of blood pressure and proteinuria is recommended.

Recurrent IgA nephropathy in renal transplant allografts.

Previous reports of renal transplantation for patients with underlying immunoglobulin A (IgA) nephropathy suggested a recurrence rate greater than 50% for transplant IgA nephropathy. Initially regarded as a benign condition, more recent data showed that recurrent transplant IgA nephropathy may be a significant contributor to graft loss. We performed a retrospective analysis in a single center of 48 kidney transplant recipients, all of Chinese origin, with biopsy-proven IgA nephropathy as the cause of end-stage renal failure to determine the recurrence rate of IgA nephropathy in the transplant allograft and subsequent clinical course in Chinese patients. Median duration of follow-up was 52 months (range, 18 to 155 months). Fourteen patients (29%) had biopsy-confirmed recurrent transplant IgA nephropathy after a median of 52 months (interquartile range, 23 to 82 months) posttransplantation. Recurrent transplant IgA nephropathy was associated with greater serum IgA levels (P = 0.01). The presence of HLA-A2 in transplant recipients (P = 0.002) appeared to protect them from developing recurrent IgA nephropathy in the transplant allograft. Twenty-nine percent of patients with recurrent transplant IgA nephropathy had progressive deterioration of graft function. The progressive graft dysfunction (GD) rate was greater in patients with a transplant from a living related donor (LRD; 21%) compared with those with a transplant from a cadaveric or living unrelated donor (URD; 3%; P = 0.062). Although the cumulative graft survival rate was 100% at 5 years for transplants from both LRDs and URDs, the 10-year graft survival rate was only 63% for a graft from an LRD versus 93% for a URD (log-rank test, P = 0.19). A review of other reported series of recurrent transplant IgA nephropathy also showed an apparently greater incidence of GD for a graft from an LRD (28%) compared with a URD (15%). Our data suggest that although recurrent transplant IgA nephropathy is highly prevalent among the Chinese population, the risk for disease recurrence is not particularly increased compared with other ethnic groups. The trend toward a greater risk for GD for living related compared with unrelated allografts in patients with IgA nephropathy needs to be confirmed with further prospective study.

Characterization of early IgA nephropathy.

Histological grading of 45 patients with clinical early immunoglobulin A (IgA) nephropathy was correlated with disease progression over a median follow-up of 123 months. Clinical early IgA nephropathy was defined as a serum creatinine level of 1.3 mg/dL or less, proteinuria of 0.4 g/d or less of protein, and the absence of hypertension at the time of renal biopsy. Disease progression was related to the occurrence of impaired renal function, increased proteinuria, and hypertension. We applied a previously described chronicity-based histological grading to the renal biopsy specimen and also assessed acute glomerular lesions. Disease progression was observed in 44.4% of these patients. Forty patients (89%) showed glomerular grade 1 (GG1) and 5 patients (11%) showed GG2, but this grading did not correlate with disease progression. However, when GG1 was subdivided into GG1a (mean sclerosis per glomerulus <10%) and GG1b (mean sclerosis per glomerulus 10% to <25%), GG1a correlated with nonprogressive disease. Tubulointerstitial grade also correlated with disease progression but was associated with a low sensitivity for predicting nonprogressive disease. Hyaline arteriolosclerosis and acute glomerular lesions did not correlate with disease progression. The chronicity-based histological grading is not only applicable to clinical early IgA nephropathy, but also more importantly, it characterizes GG1a in a subset of patients with a very low risk for disease progression, which can be regarded as genuine early IgA nephropathy.

Outcome of IgA nephropathy in adults graded by chronic histological lesions.

This prognostic study of primary immunoglobulin A (IgA) nephropathy focused on chronic irreversible glomerular sclerosis and interstitial fibrosis, based on the premise that this disease is characterized by a protracted and, for many, progressive course. We used a chronicity-based histological grading system to assess the biopsy specimens of 126 adults with IgA nephropathy over a median follow-up of 10 years. Our grading system included a glomerular grading (GG) of 1 to 3 based on the extent of glomerular sclerosis, a tubulointerstitial grading (TIG) of 1 to 3 based on the degree of tubular loss or interstitial fibrosis, and the evaluation of hyaline arteriolosclerosis (HA). These three histological parameters were correlated with each other and with serum creatinine level, degree of proteinuria, and blood pressure at the time of renal biopsy. Univariate analysis showed that these three histological and three clinical parameters were significantly correlated with renal survival. By multivariate analysis using the Cox regression model, GG, serum creatinine level, and degree of proteinuria represented independent prognostic factors of renal survival. For a subset of patients at a relatively early stage of disease with a serum creatinine level less than 130 micromol/L at the time of biopsy, all three histological features and degree of proteinuria were significantly correlated with renal survival, and GG was the only independent prognostic factor for renal outcome. This study shows that glomerular sclerosis represents the most important prognostic factor in adult patients with primary IgA nephropathy and has a strong predictive value. Our chronicity-based histological grading system not only correlates well with the natural history of IgA nephropathy but is also reproducible and relatively simple to apply.

Acute renal failure in a patient with Rosai-Dorfman disease.

Acute renal failure developed in a 57-year-old woman who had Rosai-Dorfman disease diagnosed 1 year previously on a cervical lymph node. Organ imaging showed diffuse masses infiltrating both kidneys. The renal biopsy showed a lymphoplasmacytic and histiocytic process extensively replacing the parenchyma, which is in keeping with Rosai-Dorfman disease of the kidneys. However, the typical lymphophagocytic cells were lacking. This case illustrates that diagnosis of Rosai-Dorfman disease in renal biopsy can be very difficult, requiring both exclusion of many benign and malignant lesions and a high index of suspicion for this condition. In particular, lymphoma was excluded based on the mixed polyclonal composition of inflammatory cells and the absence of atypical lymphoid proliferation. The renal function partially recovered after a course of therapy combining VP-16 (etoposide) and dexamethasone and remained stable over 4-year follow-up. This report emphasizes the importance of early diagnosis and intervention to safeguard renal function in extensive Rosai-Dorfman disease.

Metastatic solitary fibrous tumor of the meninges. Case report.

Solitary fibrous tumor (SFT) is a unique tumor composed of interstitial dendritic cells that was first described in the thorax and subsequently reported in diverse organs. Extrathoracic SFTs are predominantly benign but rare malignant cases have been documented. In the nervous system, SFT has been described as a meningeal lesion although all 14 previously reported cases were benign. The authors report the first case of a meningeal SFT occurring in a 55-year-old woman. The tumor first presented as a meningeal lesion that after three recurrences over a 10-year period metastasized to the soft tissues and lungs. The potentially malignant nature of cranial SFTs, especially those with atypical histological features and high mitotic counts, should be recognized.

A prospective controlled clinical study of skin donor sites treated with a 1-4,2-acetamide-deoxy-B-D-glucan polymer: a preliminary report.

The effect of Hyphecan (1-4,2-acetamide-deoxy-B-D-glucan) on skin donor site healing was compared with the standard skin donor site dressing Kaltostat (calcium sodium alginate) in 35 burn patients with 70 skin donor sites prospectively. The median time of wound healing for the Hyphecan group was 12 days with an average of 13.1+/-4.0 days (ranged from 9 to 28 days) while the Kaltostat group had a median healing time of 12 days (ranged from 8 to 28 days) with a mean of 13.0+/-4.1 days. The difference in healing time between these two groups was statistically insignificant with a P-value of 0.95. The infection rate was 2.9% for both Hyphecan and Kaltostat. These 35 patients had been followed up from 10 to 16 months and no difference in long-term donor site morbidity between Hyphecan and Kaltostat had been observed. This finding was encouraging because the cost of Hyphecan is less than 50% of Kaltostat and it may be worthwhile to explore the clinical application of Hyphecan in other area of burns treatment.

Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B--a prospective cohort study with paired transient elastography examinations.

BACKGROUND: Metabolic syndrome is a known risk factor of cirrhosis in chronic hepatitis B (CHB). AIM: To investigate the effects of coincidental metabolic syndrome on liver fibrosis progression in treatment-naïve CHB patients. METHODS: A total of 1466 CHB patients underwent liver stiffness measurement (LSM) by transient elastography in 2006-2008; 663 patients remained treatment-naïve and had second LSM in 2010-2012. Liver fibrosis progression was defined as an increase in LSM ≥30% at the second assessment. The impact of coincidental metabolic syndrome and its factors on liver fibrosis progression were evaluated after adjustment for viral load and hepatitis activity. RESULTS: At baseline, the mean age was 43 ± 12 years, 55% were males, serum alanine aminotransferase (ALT) was 44 ± 40 IU/L, HBV DNA was 4.0 ± 2.0 log IU/mL and LSM was 6.3 ± 3.6 kPa. Metabolic syndrome was diagnosed in 80 (12%) and 142 (21%) patients at baseline and follow-up visit, respectively; 84 (13%) and 22 (3%) patients had coincidental and resolved metabolic syndrome respectively. After an interval of 44 ± 7 months, 107 (16%) patients developed liver fibrosis progression. Coincidental metabolic syndrome [adjusted odds ratio (aOR) 2.0, 95% confidence interval (CI) 1.1-3.5, P = 0.015], central obesity (aOR 2.0, 95% CI 1.0-4.1, P = 0.05) and low level of high-density lipoprotein cholesterol (aOR 1.9, 95% CI 1.0-3.7, P = 0.04) were associated with liver fibrosis progression independent of change in viral load and ALT level. The effects of coincidental metabolic syndrome were most apparent in the immune-tolerant phase. CONCLUSION: Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B infection, independent of viral load and hepatitis activity.

Non-invasive algorithm of enhanced liver fibrosis and liver stiffness measurement with transient elastography for advanced liver fibrosis in chronic hepatitis B.

BACKGROUND: The accuracy of Enhanced Liver Fibrosis (ELF; ADVIA Centaur, Siemens Healthcare Diagnostics, Tarrytown, NY, USA) in assessing liver fibrosis in chronic hepatitis B (CHB) is to be determined. AIM: To derive and validate a combined ELF-liver stiffness measurement (LSM) algorithm to predict advanced fibrosis in CHB patients. METHODS: Using the data of a previously reported cohort of 238 CHB patients, an ALT-based LSM algorithm for liver fibrosis was used as a training cohort to evaluate the performance of ELF against liver histology. The best combined ELF-LSM algorithm was then validated in new cohort of 85 CHB patients not previously reported. RESULTS: In the training cohort, LSM has better performance of diagnosing advanced (≥F3) fibrosis (area under the receiver operating characteristics curve [AUROC] 0.83, 95% confidence interval [CI 0.76-0.91] than ELF (AUROC 0.69, 95% CI 0.63-0.75). The optimal cut-off values of ELF were 8.4 to exclude advanced fibrosis, and 10.8 to confirm advanced fibrosis. In the training cohort, an ELF ≤ 8.4 had a sensitivity of 95% to exclude advanced fibrosis; an ELF > 10.8 had a specificity of 92% to confirm advanced fibrosis. In the combined algorithm, low ELF or low LSM could be used to exclude advanced fibrosis as both of them had high sensitivity (≥90%). To confirm advanced fibrosis, agreement between high ELF and high LSM could improve the negative predictive value specificity (from 65% and 74% to 80%). CONCLUSIONS: An Enhanced Liver Fibrosis - liver stiffness measurement algorithm could improve the accuracy of prediction of either ELF or LSM alone. Liver biopsy could be correctly avoided in approximately 60% of patients.

PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome.

BACKGROUND: The rs738409 GG variant in patatin-like phospholipase 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD) and disease severity. However, it remains unclear if it contributes to the development of NAFLD through affecting dietary pattern. AIM: To examine the association among PNPLA3 gene polymorphism, dietary pattern, metabolic factors and NAFLD. METHODS: Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD). Dietary nutrient intake was recorded using a locally validated food-frequency questionnaire. RESULTS: The prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls (P < 0.001). Macronutrient intake was similar among subjects with different PNPLA3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC: CG, 2.00; GG, 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC: CG, 2.22; GG, 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA3 and dietary pattern. CONCLUSIONS: The G allele in PNPLA3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors.

Assessment of non-alcoholic fatty liver disease using serum total cell death and apoptosis markers.

BACKGROUND: The diagnosis of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and fibrosis relies on liver biopsy. Non-invasive assessments are urgently needed. AIM: To evaluate cell apoptotic marker cytokeratin-18 M30 and total cell death markers cytokeratin-18 M65/M65ED for the assessment and monitoring of NAFLD. METHODS: A cohort of 147 patients with biopsy-proven NAFLD and 73 controls were enrolled, including 51 patients who received paired liver biopsies 36 months apart. Biomarkers were determined by enzyme-linked immunosorbent assay. RESULTS: M30, M65 and M65ED increased in a stepwise fashion in control subjects, patients with non-NASH, NAFLD and NASH (all P < 0.001). All biomarkers had similarly high accuracy over 0.9 in predicting NAFLD and moderate accuracy around 0.7 in predicting NASH. Among patients with paired liver biopsies, changes in M30, M65 and M65ED positively correlated with disease progression (rho = 0.42, 0.32 and 0.39; P = 0.002, 0.023 and 0.005 respectively), and only changes in M65 and M65ED correlated with fibrosis progression (rho = 0.29, 0.34; P = 0.038, 0.015 respectively). Both M30 and M65 had area under receiver-operating characteristics curve above 0.8 in predicting disease progression. At cut-off of 236 U/L, changes of M65ED had 88% NPV and 59% PPV to exclude and predict fibrosis progression. CONCLUSIONS: Cytokeratin-18 M30 and M65/M65ED have moderate accuracy in detecting non-alcoholic steatohepatitis. Changes in the biomarkers also correlate with histological progression. However, development of new biomarkers is still required to improve the diagnostic accuracy.