Detrimental effects of fresh frozen plasma transfusions on postoperative outcomes in patients undergoing liver resection for hepatocellular carcinoma.

BACKGROUND: Perioperative fresh frozen plasma (FFP) is commonly transfused to patients undergoing liver resection for hepatocellular carcinoma (HCC), but its impacts in this population remain unknown. This study aimed to investigate the association of perioperative FFP transfusion with short-term and long-term outcomes in these patients. METHODS: We retrospectively identified and retrieved clinical data for HCC patients undergoing liver resection between March, 2007 and December, 2016. Study outcomes included postoperative bacterial infection, extended length of stay (LOS) and survival. Propensity score (PS) matching was used to determine the association of FFP transfusion with each outcome. RESULTS: A total of 1427 patients were included, and 245 of them received perioperative FFP transfusions (17.2%). Patients received perioperative FFP transfusions were older, underwent liver resection in the earlier time period, and had more extensive resection, poorer clinical conditions, and higher proportions of receiving other blood components. Perioperative FFP transfusion was associated with higher odds of both postoperative bacterial infection (OR = 1.77, p = 0.020) and extended LOS (OR = 1.93, p=<0.001), and the results remained similar after PS-matching. However, perioperative FFP transfusion did not significantly affect survival in these patients (HR = 1.17, p = 0.185). A potential association of postoperative FFP transfusions and poorer 5-year but not overall survival was observed in a subgroup of patients with low postoperative albumin levels after PS-matching. CONCLUSION: Perioperative FFP transfusions were associated with poorer short-term postoperative outcomes in HCC patients undergoing liver resection, including postoperative bacterial infection and extended LOS. Reducing perioperative FFP transfusions has the potential to improve their postoperative outcomes.

Randomized trial of contrast-enhanced harmonic guidance versus fanning technique for EUS-guided fine-needle biopsy sampling of solid pancreatic lesions.

BACKGROUND AND AIMS: For EUS-guided fine-needle biopsy sampling (EUS-FNB) of solid pancreatic lesions (SPLs), the role of sampling strategy between targeted biopsy sampling and wide sampling has not been reported. This study aimed to investigate the benefits of the 2 sampling techniques on EUS-FNB using rapid on-site evaluation. METHODS: Patients with SPLs were prospectively enrolled and randomly assigned (1:1) to undergo EUS-FNB using either contrast guidance or the fanning technique. The primary outcome was the total number of passes required to establish a diagnosis, and secondary outcomes were overall diagnostic accuracy and adverse event rates. RESULTS: One hundred eighteen patients were enrolled from February 2019 to January 2021, with 59 patients assigned to each group. There was no significant difference in the total number of passes required to establish a diagnosis between the contrast and fanning groups (median, 1 [interquartile range, 1-1] vs 1 [interquartile range, 1-2], respectively; P = .629). The sensitivity, specificity, and diagnostic accuracy in the contrast group was 100%, 66.7%, and 98.3% and in the fanning group 100%, 100%, and 100%, respectively (P = 1). An SPL <4 cm (odds ratio, 2.47; 95% confidence interval, 1.05-5.81; P = .037) and macroscopic visible core length >1 cm (odds ratio, 2.89; 95% confidence interval, 1.07-7.84; P = .037) were independently associated with increased cytologic and histologic accuracy. CONCLUSIONS: The diagnostic accuracy of EUS-FNB with the fanning technique for SPLs was comparable with the contrast guidance technique. Without additional cost, EUS-FNB with the fanning technique may be preferred for SPLs. (Clinical trial registration number: NCT04924725.).

Using Ion Torrent sequencing to study genetic mutation profiles of fatal thyroid cancers.

BACKGROUND/PURPOSE: Surgery followed by radioiodine is a mainstay of treatment for thyroid cancers of follicular origins. However, about 5% of the thyroid cancers are non-operable and/or radioiodine-refractory diseases, which are either locally advanced or metastatic and result in a survival of less than 5 years. How to treat this population of thyroid cancer patients becomes a critical issue requiring further understanding of the tumor's genetic information. METHODS: We used formalin-fixed paraffin-embedded specimens of 22 fatal thyroid cancers and their corresponding non-tumor parts, if available, to yield genomic DNA, and applied the Ion Torrent™ Personal Genome Machine (IT-PGM) System (Life Technologies), a next generation sequencing technology, to interrogate 740 mutational hotspots in 46 oncogenes. We further validated the results by conventional direct sequencing. RESULTS: We confirmed 21 mutations of 11 oncogenes in the 22 fatal thyroid cancer samples. Among them, the MET p.N375S and MLH1 p.V384D mutations, each was detected in two cases, and has rarely been found to be involved in thyroid cancer pathogenesis before. We also identified homozygous PDGFRA p.V824V mutation in eight out of the 22 cases, while the non-tumor counterparts carried heterozygous PDGFRA p.V824V mutation. We noted that the Ion Torrent technique unfortunately showed high false positive rates for detecting EGFR mutations in thyroid cancers. CONCLUSION: The extensive genetic studies provide new insights to future targeted therapy in these patients. IT-PGM proved to be valuable for comprehensively searching genetic mutations in potentially fatal thyroid cancers.

Deoxyinosine repair in nuclear extracts of human cells.

BACKGROUND: Deamination of adenine can occur spontaneously under physiological conditions generating the highly mutagenic lesion, hypoxanthine. This process is enhanced by ROS from exposure of DNA to ionizing radiation, UV light, nitrous acid, or heat. Hypoxanthine in DNA can pair with cytosine which results in A:T to G:C transition mutations after DNA replication. In Escherichia coli, deoxyinosine (hypoxanthine deoxyribonucleotide, dI) is removed through an alternative excision repair pathway initiated by endonuclease V. However, the correction of dI in mammalian cells appears more complex and was not fully understood. RESULTS: All four possible dI-containing heteroduplex DNAs, including A-I, C-I, G-I, and T-I were introduced to repair reactions containing extracts from human cells. The repair reaction requires magnesium, dNTPs, and ATP as cofactors. We found G-I was the best substrate followed by T-I, A-I and C-I, respectively. Moreover, judging from the repair requirements and sensitivity to specific polymerase inhibitors, there were overlapping repair activities in processing of dI in DNA. Indeed, a hereditable non-polyposis colorectal cancer cell line (HCT116) demonstrated lower dI repair activity that was partially attributed to lack of mismatch repair. CONCLUSIONS: A plasmid-based convenient and non-radioisotopic method was created to study dI repair in human cells. Mutagenic dI lesions processed in vitro can be scored by restriction enzyme cleavage to evaluate the repair. The repair assay described in this study provides a good platform for further investigation of human repair pathways involved in dI processing and their biological significance in mutation prevention.

Tuberculosis mortality: patient characteristics and causes.

BACKGROUND: In the antibiotic era, tuberculosis (TB) still causes a substantial number of mortalities. We aimed to identify the causes and risks of death among TB patients. METHODS: Medical records of mortality cases of culture-proven TB diagnosed during 2003-2007 were reviewed. All TB deaths were classified into 2 groups (TB-related and non-TB-related), based on the underlying cause of death. RESULTS: During the study period, 2016 cases (male: 71.1%) of culture-proven TB were identified. The mean age was 59.3 (range: 0.3-96) years. The overall mortality rate was 12.3% (249 cases) and the mean age at death was 74 years; 17.3% (43 cases) of all TB deaths were TB-related. Most of the TB-related deaths occurred early (median survival: 20 days), and the patient died of septic shock. Malignancy, liver cirrhosis, renal failure, and miliary and pneumonic radiographic patterns were all independent predictors for all TB deaths. Cavitary, miliary and pneumonic radiographic patterns were all significant predictive factors for TB-related death. Extrapulmonary involvement and liver cirrhosis were also factors contributing to TB-related death. CONCLUSIONS: The majority of TB deaths were ascribed to non-TB-related causes. Managing TB as well as underlying comorbidities in a multidisciplinary approach is essential to improve the outcome of patients in an aging population. However, the clinical manifestations of patients with TB-related death vary; many progressed to fulminant septic shock requiring timely recognition with prompt treatment to prevent early death.

Patterns, effects, and thoracic volume changes of thoracoscopic pleurodesis in rabbits.

BACKGROUND: The ideal thoracoscopic pleurodesis method for preventing recurrence of spontaneous pneumothorax remains controversial. This study was conducted to compare the patterns, effects, and thoracic volume changes achieved using a variety of thoracoscopic procedures in rabbits. MATERIALS AND METHODS: Thirty-six New Zealand White rabbits were randomly assigned to undergo the following thoracoscopic procedures in the left hemithorax: (a) parietal pleural abrasion; (b) minocycline instillation; (c) combination of abrasion and minocycline; or (d) examination alone. The rabbits were euthanatized 30 days after the operation to determine pleurodesis score, area of greatest adhesion, thoracic volume change, and histopathological findings. RESULTS: Grossly, pleural abrasion produced moderate localized apical pleural symphysis with no obvious thoracic volume change. Minocycline instillation induced moderate generalized pleurodesis with a significant decrease in thoracic volume. The combination of abrasion and minocycline instillation produced the greatest generalized pleurodesis as well as a significant decrease in thoracic volume. On microscopic examination, the combination procedure produced the greatest inflammation and fibrosis of the visceral and parietal pleura. Increased intensity of pleurodesis score as well as pleural inflammation and fibrosis is associated with decreased thoracic volume. CONCLUSIONS: Thoracoscopic pleurodesis achieved using pleural abrasion and minocycline instillation induced different patterns of pleurodesis, and a combination of each method generated a synergy and produced a better pleurodesis. However, as the generalization and intensity of the pleurodesis were inversely associated with thoracic volume, the optimal method should be determined on an individual basis according to the clinical situation.

Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome.

OBJECTIVE AND BACKGROUND: Pathological changes in severe acute respiratory syndrome (SARS) suggest that SARS sequelae are associated with dysregulation of cytokine and chemokine production. To improve understanding of the immuno-pathological processes involved in lung injury associated with SARS, the temporal changes in cytokine/chemokine profiles in the sera of SARS patients were compared with those of patients with community-acquired pneumonia (CAP), according to the degree of lung involvement. METHODS: Serum levels of 11 cytokines and chemokines, in 14 patients with SARS and 24 patients with CAP, were serially checked using a bead-based multiassay system. Sera from 12 healthy subjects were used as normal controls. RESULTS: The serum levels of interferon-gamma-inducible protein-10 (IP-10), IL-2 and IL-6 were significantly elevated during SARS infection. In patients with CAP, but not in those with SARS, the levels of interferon-gamma, IL-10, IL-8 and monokine induced by interferon-gamma (MIG) were significantly elevated compared with the levels in healthy controls. Among the chemokines/cytokines, IL-6 levels correlated most strongly with radiographic scores (r=0.62). The elevation of IP-10 and IL-2 antedated the development of chest involvement and reached peak levels earlier than the radiographic scores. In contrast, the dynamic changes in IL-6, C-reactive protein and neutrophils occurred synchronously with the changes in radiographic scores. The mean ratio of IL-6 to IL-10 in SARS patients (4.84; range 0.41-21) was significantly higher than that in CAP patients (2.95; range 0.02-10.57) (P=0.04). CONCLUSIONS: The early induction of IP-10 and IL-2, as well as the subsequent over-production of IL-6 and lack of IL-10 production, probably contribute to the main immuno-pathological processes involved in lung injury in SARS. These changes in cytokine/chemokine profile are remarkably different from those observed in CAP patients.

Increased high sensitivity C-reactive protein and neutrophil count are related to increased standard cardiovascular risk factors in healthy Chinese men.

BACKGROUND: Epidemiologic data regarding the role of inflammation in atherosclerosis have been based mainly on Caucasian populations. Thus, we analyzed the cross-sectional relationships of inflammatory biomarkers to cardiovascular risk factors (CVRF) and related variables in a large group of healthy Chinese men, a population with a markedly lower heart disease mortality rate compared with Western populations. METHODS: The study consisted of 8374 men aged 20-80 who attended a voluntary health examination at a metropolitan university center between 1997 and 2002. The relationships between serum high sensitivity C-reactive protein (hsCRP), total white blood cell (WBC), neutrophil, and monocyte counts to CVRF were analyzed using multivariate linear and logistic regression analyses. Whether a dose-response effect existed between elevated levels of each marker and increasing numbers of CVRF was also evaluated. RESULTS: The distribution of hsCRP was similar to Western studies. Both multivariate regression analyses showed all four markers to have significant correlations with body mass index, triglycerides, and adverse high density lipoprotein/low density lipoprotein ratio. Smoking was associated with increased levels of all four markers. Elevated neutrophil count had the most markedly progressive dose-response effect with increasing numbers of CVRF, whereas elevated monocyte count showed a drop in risk with CVRF of five and above. CONCLUSION: We show in our study that with increasing numbers of standard CVRF, healthy Chinese men have progressive and increasing risks of having elevated levels of hsCRP, total WBC, and neutrophil counts. While the inflammatory markers surveyed were largely correlated with CVRF, the similar values of CRP between populations with divergent mortality rates suggest that a more complex relationship may exist between CRP and disease outcome. The possible utility of neutrophil count as a marker for cardiovascular disease risk in healthy men awaits further evaluation in prospective studies.

Effects of raloxifene, one of the selective estrogen receptor modulators, on pituitary-ovary axis and prolactin in postmenopausal women.

To investigate the clinical effects of raloxifene, one of the selective estrogen receptor modulators (SERMs), on the pituitary-ovary axis and prolactin, a prospective, randomized, double-blinded study on 59 healthy postmenopausal women was performed. Forty-eight women received raloxifene 60 mg daily. The other 11 received combined conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 5 mg daily (CCEP) as active controls. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and pro-lactin were measured at baseline and 1 yr after treatment. The mean levels of FSH and LH were significantly decreased in the raloxifene group (FSH: -10.7%; p < 0.01, LH: -10.3%; p < 0.05) and CCEP group (FSH: -53.7%, p < 0.001; LH: -46.8%, p < 0.001). The prolactin level decreased in the raloxifene group but not in the CCEP group (-17.0%; p < 0.001 vs +13.3%, p = no significance; NS). Consequently, long-term administration of raloxifene up to 1 yr decreases serum prolactin level significantly and may be a therapeutic alternative for postmenopausal osteoporotic women with hyperprolactinemia.

Patient data, early SARS epidemic, Taiwan.

Of the first 10 patients in the epidemic of severe acute respiratory syndrome (SARS) in Taiwan, 4 were closely associated with a SARS patient in an airplane. Loose stools or diarrhea, hemophagocytosis syndrome, and high serum levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-a associated with lung lesions were found in all 10 patients.

Laboratory and clinical characterization of monoclonal gammopathy in Taiwanese.

BACKGROUND AND PURPOSE: To investigate the prevalence of monoclonal gammopathy, the frequency of associated diseases, and the laboratory features useful in the differential diagnosis and prediction of associated complications. MATERIALS AND METHODS: From January 1994 through December 1998, 11,510 serum samples and 1,555 urine samples from 10,974 Taiwanese patients requiring electrophoresis study were examined for the presence of monoclonal protein by electrophoresis on cellulose acetate membrane and immunofixation electrophoresis (IFE). RESULTS: Two hundred and eighty seven cases (2.6%) of monoclonal gammopathy were found. Of these, 136 (47.4%) had multiple myeloma, 84 (29.3%) had monoclonal gammopathy of undetermined significance (MGUS), 53 (18.5%) had other lymphoproliferative disorders (LPD), eight (2.8%) had polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin pigmentation (POEMS) syndrome, and six (2.1%) had cryoglobulinemia. Immunoglobulin A (IgA) monoclonal protein was more often associated with myeloma than LPD (25 vs 3.8%, p = 0.002); monoclonal light chains were more often associated with myeloma than MGUS (17% vs 3.6%, p = 0.006). Biclonal gammopathy was more often associated with MGUS than myeloma (10.7 vs 1.5%, p = 0.014). Hypogammaglobulinemia was common in patients with myeloma (70%) but rare in patients with LPD (20%, p < 0.001) and in those with MGUS (5%, p < 0.001). Concomitant polyclonal hypergammaglobulinemia was rare in patients with myeloma (5%), but common in patients with LPD (53%, p < 0.001) or MGUS (27%, p < 0.001). Patients with lambda chain myeloma had the highest risk (100%) of developing renal insufficiency. Our myeloma patients were also at increased risk of developing myelomatous pleural effusions than previously reported. CONCLUSIONS: The lower frequency of MGUS in this study than previously reported may have been due to differences in patient selection, laboratory methods, and the presence of local diseases. The presence of POEMS syndrome and cryoglobulinemia, the very high association of lambda chain myeloma with renal failure, and the higher occurrence of myelomatous effusion than previously reported probably reflected local disease patterns.