The efficacy and tolerability of bortezomib, thalidomide, and dexamethasone induction therapy with a thalidomide dose step-up strategy in patients with newly diagnosed multiple myeloma: A prospective observational study.

BACKGROUND: Thalidomide-containing regimens cause adverse events (AEs) that may require a reduction in treatment intensity or even treatment discontinuation in patients with multiple myeloma. As thalidomide toxicity is dose-dependent, identifying the most appropriate dose for each patient is essential. AIMS: This study aimed to investigate the effects of a thalidomide dose step-up strategy on treatment response and progression-free survival (PFS). METHODS AND RESULTS: This prospective observational study included 93 patients with newly diagnosed multiple myeloma (NDMM) who received bortezomib, thalidomide, and dexamethasone (VTD). The present study assessed the incidence of thalidomide dose reduction and discontinuation, the overall dose intensity, and their effects on therapeutic efficacy. Furthermore, this study used Cox proportional hazard models to analyze the factors contributing to thalidomide intolerability. The results showed the overall response rates in all patients and the evaluable patients were 78.5% and 98.7%, respectively. The median PFS in the study cohort was not reached. The most common thalidomide-related AEs were constipation (32.3%) and skin rash (23.7%), resulting in dose reduction and discontinuation rates of 22.6% and 21.5%, respectively. The responders had a significantly higher average thalidomide dose intensity than the nonresponders (88.6% vs. 42.9%, p < .001). CONCLUSION: The thalidomide dose step-up approach is a viable option for patients with NDMM receiving VTD induction therapy with satisfactory efficacy and tolerability. However, thalidomide intolerance may lead to dose reduction or discontinuation due to unpredictable AEs, leading to lower dose intensity and potentially inferior treatment outcomes. In addition to a dose step-up strategy, optimal supportive care is critical for patients with multiple myeloma receiving VTD induction therapy.

The concomitant use of the renin-angiotensin system inhibitors and survival outcomes of patients with pancreatic adenocarcinoma: an analysis from a tertiary center.

Background: The limited efficacy of chemotherapy in improving survival in pancreatic ductal adenocarcinoma (PDAC) necessitates the exploration of novel strategies to overcome treatment resistance. Objectives: This study aimed to investigate the impact of combining renin-angiotensin system (RAS) blockers with chemotherapy on survival outcomes in patients with PDAC. Design: Patients with PDAC were enrolled in the retrospective study. Methods: We analyzed patients with PDAC (n = 384) at our institution between 2014 and 2021. Survival outcomes, including event-free survival (EFS) and overall survival (OS), were analyzed according to the concomitant use of RAS blockers. Results: Among the 384 patients in the study, 70 (18.2%) concomitantly received angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Patients in the ACEI/ARB group, characterized by older age and more comorbidities, displayed a significantly superior 12-month EFS rate (22.86% versus 13.69%, p = 0.008) compared to the non-ACEI/ARB group, while OS remained similar between the groups. In the multivariate analysis, the use of ACEI/ARB was associated with better 12-month EFS (hazards ratio = 0.71, 95% confidence interval: 0.52-0.96; p = 0.024). Poor performance, advanced disease status, and higher CA19-9 levels were associated with poor survival outcomes. Conclusion: Concomitant use of ACEIs/ARBs in patients with pancreatic cancer resulted in significantly better 12-month EFS. Age, performance status, disease status, and higher CA19-9 levels were independent predictors of survival. The combination strategy might provide better treatment outcomes in patients with PDAC.

The efficacy of adjuvant chemotherapy for older adults with stage II/III gastric cancer: a retrospective cohort study.

BACKGROUND: Adjuvant chemotherapy is recommended as the standard treatment for patients with stage II/III resected gastric cancer. However, it is unclear whether older patients also benefit from an adjuvant chemotherapy strategy. This study aimed to investigate the clinical impact of adjuvant chemotherapy in older patients with stage II/III gastric cancer. METHODS: This retrospective, real-world study analyzed 404 patients with stage II/III gastric cancer visited at our institute between January 2009 and December 2019. The clinical characteristics and outcomes of patients aged 70 years or older who received adjuvant chemotherapy were compared with those who did not receive this type of treatment. Propensity score analysis was performed to mitigate selection bias. RESULTS: Of the 404 patients analyzed, 179 were aged 70 years or older. Fewer older patients received adjuvant chemotherapy than did younger patients (60.9% vs. 94.7%, respectively; P < 0.001). Among patients aged 70 years or older, those who received adjuvant chemotherapy had improved disease-free survival (DFS) (5-year DFS rate, 53.1% vs. 30.4%; P < 0.001) and overall survival (OS) (5-year OS rate, 68.7% vs. 52.1%; P = 0.002) compared to those who did not receive adjuvant chemotherapy. A similar survival benefit was observed in the propensity-matched cohort. Multivariate analysis showed that more advanced stage was associated with poorer OS. Receipt of adjuvant chemotherapy was independently associated with a decreased hazard of death (hazard ratio (HR), 0.37; 95% confidence intervals (CI), 0.20-0.68; P = 0.002). CONCLUSIONS: Adjuvant chemotherapy may benefit older stage II/III gastric cancer patients aged ≥ 70 years. Further prospective studies are needed to confirm these findings.

Estimated exposure to perfluoroalkyl substances during infancy and serum-adipokine concentrations in later childhood.

BACKGROUND: Perfluoroalkyl substances (PFASs) are transferred through human milk and may cause elevated exposure during infancy. Given the lack of early postnatal blood samples, PFAS concentrations can be estimated to serve as predictors of subsequent metabolic toxicity. METHODS: A total of 298 children from a prospective birth cohort were followed up through to age 9 years. Serum-PFAS was measured at birth and 18 months of age, while exposures during infancy were estimated by structural equations. Adiponectin, resistin, leptin, and the leptin receptor were measured in serum at age 9. Adjusted regression coefficients for estimated serum-PFAS concentrations were calculated, with additional consideration of the duration of breastfeeding and potential effect modification by sex. RESULTS: A doubling in estimated serum-PFAS concentrations, particularly at ages 6 and 12 months, was associated with a loss of about 10-15% in age 9 resistin concentrations, while other associations were much weaker. Sex dependence of the associations was not observed, and neither did the duration of breastfeeding affect outcomes at age 9. CONCLUSION: Lowered serum-resistin concentrations at age 9 years were most strongly associated with early postnatal PFAS exposures. These findings suggest that infancy may represent a vulnerable time window for some aspects of metabolic programming that may be affected by PFAS exposure. IMPACT: Serum-PFAS concentrations during infancy can be estimated in the absence of blood samples. Adipokine concentrations were measured at age 9 years as metabolic biomarkers. Resistin was significantly lower in children with elevated PFAS exposures in infancy. The findings suggest that early postnatal PFAS exposures may affect subsequent metabolic health. Assessment of infancy vulnerability to PFAS can be explored using estimated serum-PFAS concentrations.

Survival outcomes of patients with head and neck squamous cell cancer with hepatitis B virus infection: An analysis from an endemic tertiary center.

BACKGROUND: Hepatitis B virus (HBV) affects the occurrence and survival outcome of various malignant disorders. The study aimed to evaluate the survival outcome of head and neck squamous cell cancer (HNSCC) patients with or without HBV infection. METHODS: This study included patients with HNSCC who visited Taichung Veterans General Hospital from 2007 to 2015. HBV infection was defined by hepatitis B surface antigen (HBsAg) seropositivity. By propensity score matching, we compared survival outcomes, including progression-free survival (PFS) and overall survival (OS), among patients with or without HBV infection. RESULTS: The prevalence of HBV infection in our cohort was 12.3%. Among the 1,015 patients included in the matched analysis, a higher risk of baseline liver cirrhosis (11.3% vs. 3.4%, p < 0.001) and initial hepatic dysfunction (10.8% vs. 5.4%, p = 0.005) rates were observed than those without HBV infection at baseline. The 5-year OS was 43.1% and 53.2% (p < 0.001) and the 5-year PFS was 37.4% and 42.3% (p = 0.007) in patients with and without HBV infection, respectively. The incidence of subsequent hepatic dysfunction showed no difference between patients with and without HBV infection (29.6% vs. 26.8%, p = 0.439). CONCLUSIONS: Patients with HNSCC and HBV infection were younger and had a higher risk of cirrhosis compared to those without HBV infection. Moreover, HBV infection significantly influenced the OS and PFS outcomes but not subsequent hepatic dysfunction in patients with HNSCC.

Detection of DLBCL by pixel purity index and iterative linearly constrained minimum variance into hyperspectral imaging analysis.

It is unclear whether a hyperspectral imaging-based approach can facilitate the diagnosis of diffuse large B-cell lymphoma (DLBCL), and further investigation is required. In this study, the pixel purity index (PPI) coupled with iterative linearly constrained minimum variance (ILCMV) was used to bridge this gap. We retrospectively reviewed 22 pathological DLBCL specimens. Ten normal lymph node specimens were used as controls. PPI endmember extraction was performed to identify seed-training samples. ILCMV was then used to classify cell regions. The 3D receiver operating characteristic (ROC) showed that the spectral information divergence possessed superior ability to distinguish between normal and abnormal lymphoid cells owing to its stronger background suppression compared with the spectral angle mapper and mean square error methods. An automated cell hyperspectral image classification approach that combined the PPI and ILCMV was used to improve DLBCL diagnosis. This strategy intelligently resolved critical problems arising in unsupervised classification.

Chemotherapy for Metastatic Gastric Cancer: Does Age Matter? A Single-Center, Retrospective, Real-World Study.

Background: Palliative chemotherapy is the preferred standard of care for patients with metastatic gastric cancer (mGC). It remains uncertain whether older patients with mGC would benefit from palliative chemotherapy. This study aimed to investigate the clinical impact of palliative chemotherapy in older patients with mGC. Methods: This single-institute, retrospective, and real-world study included 428 patients with mGC between January 2009 and December 2019. Among them, 306 who received palliative chemotherapy were further stratified into 2 groups according to age: ≤70 (n = 236) and >70 (n = 70) years. The clinical demographics, outcomes, and hematologic toxicities of chemotherapy were compared between the 2 groups. Prognostic factors were determined using the Cox proportional hazards model. Results: Of the screened 428 patients, older patients had worse overall survival (OS) than younger patients. Among patients who received chemotherapy (n = 306), patients aged >70 and ⩽70 years had comparable progression-free survival (PFS) and OS. The incidence of severe hematologic toxicity was similar between the 2 groups. The Eastern Cooperative Oncology Group performance status of 2 or more metastatic sites, elevated carbohydrate antigen 19-9 level, high neutrophil-to-lymphocyte ratio (NLR), and undergoing palliative gastrectomy were independent prognostic factors for OS. Notably, age >70 years was not a significant factor for poor OS. Conclusions: Older age of >70 years might not be considered an obstacle to administering palliative chemotherapy to patients with mGC.

Clinical Features and Immunophenotypes of Double-Hit Diffuse Large B-Cell Lymphoma.

Double-hit (DH) genetics induces a reduction in the complete remission (CR) and, consequently, in poor overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. Unfortunately, DH identification is time-consuming. Here, we retrospectively reviewed 92 newly diagnosed DLBCL patients, stratified them into the DH (n = 14) and non-DH groups (n = 78), and compared their clinical features and outcomes. The results revealed that the DH group had a higher percentage of bulky disease than the non-DH group (64.3% vs. 28.2%; p = 0.013). More patients in the DH group tested positive for double expresser (DE) (50.0% vs. 21.8%; p = 0.044). The three-year OS rates of patients with and without DH were 33.3% and 52.2%, respectively (p = 0.016). Importantly, advance stage and multiple comorbidities were correlated with a high mortality rate in multivariate analysis. Furthermore, by combining DE and the bulky disease, a specificity of 89.7% for DH prediction was achieved. In summary, DH genetics, not DE immunopositivity, could be a factor for an inferior OS in DLBCL. A combination of bulky disease and a positive DE immunophenotype could facilitate DH genetics prediction in newly diagnosed DLBCL patients.

Acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation: a retrospective study from a single institution.

OBJECTIVE: The outcomes of patients with acute myeloid leukemia (AML) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are poor. However, the risk factors for relapse in this context remain unclear. METHODS: We retrospectively assessed 84 consecutive adult AML patients who underwent allo-HSCT and achieved complete remission (CR). These patients were dichotomized into non-relapse (n = 58) and relapse (n = 26) groups, and the cumulative relapse rates and associated risk factors were examined. We also examined the treatments for and outcomes of patients with AML relapse after allo-HSCT. RESULTS: Non-CR status before allo-HSCT and high-risk cytogenetics were significant risk factors for AML relapse in univariate analysis, and non-CR status was also identified as a risk factor in multivariate analysis. The cumulative AML relapse rates after allo-HSCT were significantly higher in patients with non-CR (70.0%) compared with patients with CR (25.6%). Only 2 of the 26 relapsed patients remained alive on the study-censored day. CONCLUSIONS: Non-CR status before allo-HSCT was a significant risk factor for AML relapse after allo-HSCT. Patients with AML relapse after allo-HSCT had poor outcomes due to a lack of response to salvage remission-induction chemotherapy or treatment-related adverse events.

Dual-lumen power injectable peripherally inserted central catheters in allogeneic hematopoietic stem cell transplantation: A prospective observational study.

AIMS AND OBJECTIVES: To explore whether dual-lumen power injectable peripherally inserted central catheters (PICCs) could be effectively and safely applied in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and for serum cyclosporine level monitoring. BACKGROUND: Compared to conventional central venous access devices, PICC provides a feasible route not only for fluid infusion, but also for blood sample collection in patients undergoing oncological treatments. DESIGN: A prospective observational study was conducted according to the STROBE guidelines. METHODS: We prospectively evaluated the applications and complications of power injectable PICCs in 52 consecutive allo-HSCT recipients. We also compared the cyclosporine levels in 188 paired blood samples, simultaneously obtained via power injectable PICCs and percutaneous venous puncture, to investigate whether power injectable PICC is a feasible route for cyclosporine concentration monitoring in allo-HSCT. RESULTS: The median PICC placement duration was 29 days. The insertion-site blood oozing and central line-associated bloodstream infection rates were 36.5% (19/52) and 26.9% (14/52), respectively, indicating the feasibility of these PICCs for various applications in allo-HSCT. No power injectable PICC-related thrombotic adverse events were identified; 90.4% (47/52) of cases with power injectable PICC removal occurred because of lack of medical utility, suggesting that power injectable PICC-related complications were manageable. However, cyclosporine levels in samples obtained via these PICCs were significantly higher than those in samples obtained via percutaneous venous puncture (261.5 ± 139.2 vs. 232.4 ± 253.6 ng/ml; p = 0.019 [set 1]; 254.8 ± 89.3 vs. 225.1 ± 233.3 ng/ml; p<0.001 [set 2]; 283.6 ± 103.9 vs. 238.0 ± 254.7 ng/ml; p = 0.006 [set 3]; 291.0 ± 94.9 vs. 266.0 ± 274.7 ng/ml; p = 0.016 [set 4]). CONCLUSION: The power injectable PICC is a feasible venous access device for allo-HSCT. RELEVANCE TO CLINICAL PRACTICE: The dual-lumen power injectable PICCs provided a reliable access for blood sample collection, decreasing the number of blind percutaneous venous punctures in allo-HSCT. However, its application in cyclosporine level monitoring needs further investigation.

Redefining Remission Induction Chemotherapy Ineligibility by Early Mortality in De Novo Acute Myeloid Leukemia.

The therapeutic strategies for acute myeloid leukemia (AML) patients ineligible for remission induction chemotherapy have been improving in the past decade. Therefore, it is important to define ineligibility for remission induction chemotherapy. We retrospectively assessed 153 consecutive adult de novo AML patients undergoing remission induction chemotherapy and defined early mortality as death within the first 60 days of treatment. The 153 patients were stratified into the early mortality group (n = 29) and the non-early mortality group (n = 124). We identified potential factors to which early mortality could be attributed, investigated the cumulative incidence of early mortality for each aspect, and quantified the elements. The early mortality rate in our study cohort was 19.0%. Age ≥ 65 years (odds ratio (OR): 3.15; 95% confidence interval (CI): 1.05-9.44; p = 0.041), Eastern Cooperative Oncology Group performance status ≥ 2 (OR: 4.87; 95% CI: 1.77-13.41; p = 0.002), and lactate dehydrogenase ≥ 1000 IU/L (OR: 4.20; 95% CI: 1.57-11.23; p = 0.004) were the risk factors that substantially increased early mortality in AML patients. Patients with two risk factors had a significantly higher early mortality rate than those with one risk factor (68.8% vs. 20.0%; p < 0.001) or no risk factors (68.8% vs. 9.2%; p < 0.001). In conclusion, older age, poor clinical performance, and a high tumor burden were risks for early mortality in AML patients receiving remission induction chemotherapy. Patients harboring at least two of these three factors should be more carefully assessed for remission induction chemotherapy.

A Decade of Lymphoma-Associated Hemophagocytic Lymphohistiocytosis: Does the Outcome Improve?

To investigate the potential treatment evolution and outcome improvement, we retrospectively compared clinical characteristics, therapeutic strategies, treatment responses, and overall survival (OS) in patients diagnosed and treated with lymphoma-associated HLH between 2004-2012 (n = 30) and 2013-2021 (n = 26). Our study showed that the clinical characteristics of lymphoma-associated HLH did not substantially change over the past two decades. However, more patients diagnosed in 2013-2021 were tested for Epstein-Barr virus than those diagnosed in 2004-2012 (69.3% vs. 33.3%; p = 0.021). In addition, Eastern Cooperative Oncology Group performance status 3-4 (hazard ratio (HR): 5.38; 95% confidence intervals (CI): 2.49-11.61; p < 0.001) and jaundice (HR: 2.91; 95% CI: 1.37-6.18; p = 0.006) were poor prognostic factors for lymphoma-associated HLH. With a comparable response rate of lymphoma treatment, patients treated in 2013-2021 had a numerically greater median OS than those treated in 2004-2012 (23.6 ± 19.8 vs. 9.7 ± 4.5 months). However, the difference was not statistically significant (p = 0.334). In conclusion, early diagnosis and tailored treatments that balance efficacy and adverse events remain the key to obtaining a better outcome in lymphoma-associated HLH.

Assessment of the Antibacterial Mechanism of Pterostilbene against Bacillus cereus through Apoptosis-like Cell Death and Evaluation of Its Beneficial Effects on the Gut Microbiota.

Foods contaminated by harmful substances such as bacteria and viruses have caused more than 200 kinds of diseases, ranging from diarrhea to cancer. Among them, Bacillus cereus (B. cereus) is a foodborne pathogen that commonly contaminates raw meat, fresh vegetables, rice, and uncooked food. The current chemical preservatives may have adverse effects on food and even human health. Therefore, natural antibacterial agents are sought after as alternative preservatives. Stilbene compounds, including pterostilbene (PT), pinostilbene (PS), and piceatannol (PIC), which have many health benefits and exhibit antibacterial activity, were tested against B. cereus. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of PT, PS, and PIC against B. cereus ranged from 25 to 100 µg/mL. From the time-kill curve assay, PT reduced B. cereus cell survival, increased intracellular reactive oxygen species (ROS), and induced apoptosis-like cell death (ALD) in a dose-dependent manner. The quantitative real-time polymerase chain reaction (qPCR) results confirmed that treatment with PT induced genetic changes related to ALD, such as an increase in RecA gene expression and a decrease in LexA gene expression. In addition, PT showed a beneficial effect on the gut microbiota that increased the abundance of Bacteroidetes and lowered the abundance of Firmicutes. Taken together, our results showed that PT has antibacterial effects against B. cereus via ALD and is beneficial for promoting healthy gut microbiota that is worthy for the development of antibacterial agents for the food industry.

Urinary arsenic concentration, airway inflammation, and lung function in the U.S. adult population.

BACKGROUND: Inorganic arsenic (iAs) is ubiquitous in the environment and has been linked to lung cancer and a number of non-malignant lung disease in both adults and children. However, most studies were conducted in populations with higher arsenic exposure levels in drinking water and relatively little epidemiologic research evaluated the impacts of low levels iAs exposure on non-malignant lung disease among populations that are not primarily exposed to arsenic through drinking water. OBJECTIVES: We assessed the associations of arsenic exposure with airway inflammation and lung function among U.S. adults aged 20-79 years using data from the National Health and Nutrition Examination Survey 2007-2012 cycles. METHODS: Two measures of arsenic exposure, urinary total arsenic and dimethylarsonic acid (DMA), were used. We calibrated these two exposure measures by regressing their concentrations by arsenobetaine and extracting the residuals to calculate estimated total arsenic and estimated DMA. Arsenic exposures were modeled as log-transformed continuous variables as well as quartile categories. Fractional exhaled nitric oxide (FENO), an indicator of respiratory inflammation, was available for participants. For lung function, the best forced expiratory volume in the first one second (FEV1), forced vital capacity (FVC), forced expiratory flow rate (FEF) 25-75%, their percent estimated values, ratios of FEV1 to FVC, and FEF 25-75% to FVC were used (i.e. FEV1/FVC and FEF/FVC). Weighted multivariable linear regression models, adjusted for potential confounders, were used to evaluate the association of arsenic exposure with airway inflammation and lung function overall, and among males and females. RESULTS: Significant associations between arsenic exposure and increased airway inflammation were found. A two-fold increase in urinary total arsenic and DMA was associated with 23.87% (95% CI: 2.66, 49.46) and 14.05% (95% CI: 1.77, 27.81) higher levels of FENO, respectively. In addition, participants in the highest quartile of urinary total arsenic had FENO levels 8.49% (95% CI: 1.13, 16.39) higher than those in the lowest quartile. These associations were similar between males and females. Limited evidence was found for the association with respect to lung function and potential modification effect of sex. CONCLUSIONS: Arsenic exposure was related to increased risk of airway inflammation but there is limited evidence of an association in relation to lung function. Future research conducted in populations with relatively lower exposure levels that are not primarily exposed to arsenic through drinking water is needed to confirm our findings.

Clinical features and outcome of lymphoma patients with pre-existing autoimmune diseases.

AIMS: Previous epidemiological studies have shown that autoimmune diseases increase the risk of lymphoma development. However, whether autoimmune diseases deteriorate the outcomes for lymphoma patients remains unclear. This study aimed to identify the clinical features of lymphoma patients with pre-existing autoimmune diseases. Whether pre-existing autoimmune diseases impacted progression-free survival (PFS) and overall survival (OS) in lymphoma patients was further investigated. METHODS: We retrospectively reviewed medical records of 913 newly diagnosed lymphoma patients from January 2008 to November 2016. Thirty-four lymphoma patients with pre-existing autoimmune disorders were identified. Six of these 34 patients were lost to follow-up; their data was used to examine baseline clinical characteristics but not survival. Therefore, 28 lymphoma patients with autoimmune diseases were included in the autoimmune disease group for comparing the remission rate, PFS and OS to lymphoma patients without autoimmune diseases (control group; n = 56). RESULTS: Diffuse large B-cell lymphoma was the most common histological subtype (18/34; 52.94%). Complete remission rates in the autoimmune disease and control groups were 72.0% and 83.3%, respectively (P = 0.178). Patients with and without autoimmune diseases had similar PFS (45.4 ± 59.9 months vs. 51.5 ± 42.8 months; P = 0.398) and OS (46.4 ± 52.6 months vs. 50.1 ± 47.3 months; P = 0.352). By univariate analysis, pre-existing autoimmune diseases were not associated with inferior PFS (P = 0.326) or OS (P = 0.627). CONCLUSIONS: Lymphoma patients with and without autoimmune disorders had comparable outcomes. Autoimmune diseases are not an obstacle to lymphoma treatment.

Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality.

BACKGROUND: Chronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established. OBJECTIVES: We evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh. METHODS: Creatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality. RESULTS: We observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure. CONCLUSIONS: Prospective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age.

Epidural anesthesia for laparoscopic bariatric surgery: a case report.

BACKGROUND: Rapid and uneventful postoperative recovery following general anesthesia in morbidly obese patients undergoing bariatric surgery may offer challenges to anesthesiologists. With improved surgical techniques and shorter pneumoperitoneum, regional anesthesia may be considered for this laparoscopic procedure in selected cases. CASE DESCRIPTION: The first patient was a 60-year-old male (body mass index: 39 kg/m(2)) who was scheduled for laparoscopic sleeve gastrectomy. The second patient was a 46-year-old female (body mass index: 47 kg/m(2)) who was scheduled for laparoscopic gastric bypass. After standard intraoperative monitoring was applied, epidural anesthesia was performed at thoracic level T9-T10. Surgical technique modification included insufflation of CO2 at a low flow rate and avoidance of orogastric tube use. During the procedure, both patients breathed spontaneously without difficulty. One hypotension episode occurred and was successfully treated with a 12-mg bolus of ephedrine in case 1. Shoulder pain occurred intraoperatively in case 2 and was successfully treated with a 50-µg bolus of fentanyl. Postoperatively, 2 mg epidural morphine was administered for postoperative analgesia. Both patients were satisfied with the anesthesia technique and was discharged uneventfully. DISCUSSION AND EVALUATION: This anesthetic technique may maintain pre-operative respiratory function, increase alertness, and reduce the use of rescue analgesics, which is crucial for optimal outcomes in morbidly obese patients. Conversion of epidural anesthesia to general anesthesia may be required if patients can not tolerate the laparoscopic procedure (e.g. intolerable shoulder pain) or the increased respiratory rate during pneumoperitoneum leading to difficulty in performing laparoscopic surgery. Further studies are needed to elucidate this issue. CONCLUSIONS: General anesthesia is widely used for laparoscopic bariatric surgery, but epidural anesthesia may be a viable alternative to general anesthesia in selected cases. Further prospective studies may be required to elucidate the relative advantages and disadvantages of epidural anesthesia in this surgical population.

Using a modified syringe technique to adjust the intracuff pressure of a laryngeal mask airway.

Limiting the intracuff pressure of a laryngeal mask airway (LMA) to <60 cmH2O is recommended in clinical practice. This report aimed to assess the efficacy of a modified syringe technique to adjust the intracuff pressure of an LMA. In a preclinical study, commercially available 20-mL syringes were attached to the pilot balloon of LMAs with different preset intracuff pressures (40 cmH2O, 50 cmH2O, 60 cmH2O, 70 cmH2O, 80 cmH2O, 100 cmH2O, and 120 cmH2O). After attachment, the syringe plunger was allowed to passively rebound. If no rebound of the plunger was observed after attachment, 1 mL of air was withdrawn and the plunger was allowed to passively rebound again. This technique allowed the plunger to overcome static friction and avoid excessive deflation of the LMA cuffs. The intracuff pressure was measured using a manometer after the plunger ceased moving. In the preclinical study, the intracuff pressure was always less than or close to 60 cmH2O after adjustment using this modified syringe technique. After evaluating the performance and characteristics of the syringe in the preclinical study, we concluded that the modified syringe technique may be useful for adjusting LMA intracuff pressure effectively.