Impact of CYP2C19 metabolizer status on esophageal mucosal inflammation, acid exposure, and motility among patients on chronic proton-pump inhibitor therapy with refractory symptoms of gastroesophageal reflux disease.

Background: The extent of disease severity remains unclear among CYP2C19 rapid and ultra-rapid metabolizers with refractory symptoms of gastroesophageal reflux disease (GERD) on chronic proton-pump inhibitors (PPIs). Aims: To determine the impact of CYP2C19 metabolizer status in relation to chronic PPI therapy with a focus on the extent of esophageal inflammation, acid exposure, and motor function. Methods: This retrospective study included 54 patients with refractory GERD symptoms who underwent CYP2C19 genotyping for PPI metabolism, esophagogastroduodenoscopy, ambulatory pH study, and high-resolution esophageal manometry. Patients were divided into three groups: normal metabolizer (NM) group, intermediate metabolizer/poor metabolizer (IM/PM) group, and rapid metabolizer/ultra-rapid metabolizer (RM/UM) group. The Chi-square test was used to analyze categorical variables, and one-way ANOVA for comparing means. Results: Rapid metabolizer/ultra-rapid metabolizer (RM/UM) group more frequently had either Los Angeles grade C or D GERD (7/19, 36.8% vs 1/21, 4.8%, P = 0.011) and metaplasia of the esophagus (9/19, 47.4% vs 2/21, 9.5%, P = 0.007) when compared to the NM group. RM/UM group were more frequently offered dilatation for nonobstructive dysphagia (8/19, 42.1% vs 3/21, 14.3%, P = 0.049) and more exhibited a hypotensive lower esophageal sphincter (LES) resting pressure compared to the NM group (10/19, 52.6% vs 4/21, 19%, P = 0.026). All three groups exhibited comparable DeMeester scores when PPIs were discontinued 72 hours before the ambulatory pH study. Conclusion: CYP2C19 RMs and UMs on chronic PPI with refractory GERD symptoms exhibited greater esophageal mucosal inflammation, as observed both endoscopically and histologically, and more were found to have hypotensive LES resting pressures and more were offered esophageal dilatation.

Granulocyte Colony Stimulating Factor-induced Immune Recovery Uveitis Associated with Cytomegalovirus Retinitis in the Setting of Good Syndrome.

PURPOSE: To report a case of immune recovery uveitis (IRU) secondary to cytomegalovirus (CMV) retinitis in a patient with Good syndrome treated with granulocyte colony stimulating factor (GCSF). METHODS: A case report. CASE: A 54-year-old woman with a history of Good syndrome for 2 years presented with chronic panuveitis in her right eye for 6 months. She had received multiple doses of GCSF for a pulmonary infection. Her visual acuity was hand movement in the right eye. Few anterior chamber cells, dense vitreous haze, and chorioretinal lesions were noted. Granular retinal atrophic lesions without obvious infiltration were observed during diagnostic vitrectomy. Polymerase chain reaction of the vitreous sample was positive for CMV DNA. A diagnosis of IRU secondary to CMV retinitis was made. The inflammation was controlled with topical steroids after surgery. SUMMARY: In this report, we present a patient with Good syndrome who developed IRU secondary to CMV retinitis.

Detection of respiratory viruses in adults with respiratory tract infection using a multiplex PCR assay at a tertiary center.

BACKGROUND: Respiratory viruses (RVs) are among the most common pathogens for both upper and lower respiratory tract infections (RTIs). However, the viral epidemiology of RV-associated RTIs in adults has long been under-recognized. Through a sensitive molecular assay, it would be possible to have a better understanding of the epidemiology of RV-associated RTIs. MATERIAL AND METHODS: Respiratory tract (RT) specimens from adults hospitalized due to RTIs were tested for RVs, using the multiplex PCR-based Luminex xTAG® Respiratory Viral Panel assay. A total of nineteen RVs, including influenza viruses and non-influenza respiratory viruses (NIRVs) were detected. Positive rates were compared using a chi-square test. RESULTS: A total of 2292 samples from adult patients hospitalized with RTIs were screened for RVs. The overall positive rate was 22%, with 17.8% samples positive for at least one NIRV. NIRVs had a higher positive rate in non-winter seasons. As many as 12.7% (46/363) of the samples collected through broncho-alveolar lavage and 20.5% (176/859) of the samples collected in ICUs were positive for RVs. Distribution of corona virus (CoV), human metapneumovirus (hMPV) and parainfluenza virus (PIV) demonstrated seasonal variation. Also, temperature was associated with the positive rates of specific viruses, including CoV, respiratory syncytial virus (RSV), hMPV and PIV. CONCLUSION: Respiratory viruses, notably NIRVs, were frequently detected in adults hospitalized with RTIs. Several RVs were detected with distinctive seasonal variations. A substantial number of RVs were identified in lower RT specimens or from patients admitted to ICU, highlighting their important role in causing severe respiratory infection.

Early echocardiographic signs of diastolic dysfunction predict acute kidney injury in cirrhotic patients.

BACKGROUND: Cardiovascular dysfunction in cirrhotic patients affects survival and the development of cirrhotic complications. We aimed to evaluate potential echocardiographic parameters to predict mortality and acute kidney injury (AKI) in cirrhotic patients. METHODS: A total of 103 cirrhotic patients who underwent echocardiography between February 2009 and August 2016 in Taipei Veterans General Hospital were retrospectively enrolled. Cardiac function was evaluated using transthoracic two-dimensional echocardiography with tissue Doppler imaging. Cox hazard regression analysis was used for assessing predictors for 1-year mortality and AKI within 1 year. RESULTS: Baseline echocardiographic parameters were similar between survivors (n = 92) and nonsurvivors (n = 11). Lower serum levels of albumin, as well as higher albumin-bilirubin (ALBI) scores, Child-Pugh scores, and model for end-stage liver disease scores were observed in nonsurvivors. Cox proportional hazard regression analysis revealed Child-Pugh score as the only predictor of 1-year mortality. Baseline serum creatinine (Cr) > 1.5 mg/dL, total bilirubin > 2 mg/dL, and a higher E/e' ratio predict occurrence of AKI within 1 year. Among patients with serum Cr < 1.5 mg/dL, an increased atrial filling velocity and higher ALBI scores predict AKI occurrence within 1 year. CONCLUSION: Severity of underlying liver disease but not echocardiographic parameters predicts 1-year mortality in cirrhosis. Early echocardiographic signs of diastolic dysfunction and higher ALBI scores may predict development of AKI in cirrhotic patients with serum Cr < 1.5 mg/dL.

Severe acute hypokalaemia associated with piperacillin/tazobactam in an HIV-infected patient under antiretroviral therapy with tenofovir alafenamide: case report and literature review.

Piperacillin/tazobactam is a commonly prescribed antimicrobial agent. Tenofovir alafenamide (TAF) is increasingly being used in antiretroviral therapy (ART) of HIV. Herein we report a case of a 57-year-old male with AIDS receiving TAF-containing ART in whom severe refractory hypokalaemia developed after coadministration of piperacillin/tazobactam for suspected hospital-acquired infection. Upon withdrawal of piperacillin/tazobactam, serum potassium concentrations returned to normal within 2 days. Hypokalaemia is a rare adverse effect of piperacillin/tazobactam and may be aggravated with the underlying use of TAF. We also reviewed past reported cases of hypokalaemia after piperacillin/tazobactam administration. We want to highlight that a more cautious approach should be considered when combining piperacillin/tazobactam and TAF in clinical practice.

Comparing Late-line Treatment Sequence of Regorafenib and Reduced-intensity FOLFOXIRI for Refractory Metastatic Colorectal Cancer.

BACKGROUND: Both regorafenib and reduced-intensity FOLFOXIRI (riFOLFOXIRI) prolong survival in patients with metastatic colorectal cancer (mCRC). However, the sequence in which they should be administrated first in late-line treatment for refractory mCRC remains unclear. PATIENTS AND METHODS: This study was a single-center retrospective cohort study that reviewed data from patients at Taipei Veterans General Hospital, Taiwan, with mCRC refractory to fluorouracil, irinotecan, oxaliplatin, cetuximab (wild-type RAS), and bevacizumab. Patients were divided into 2 groups: a regorafenib-first group and a riFOLFOXIRI-first group. The Kaplan-Meier method and log-rank test were used to analyze survival, and a Cox proportional hazards model was used for univariate, multivariate, and subgroup analyses. RESULTS: A total of 136 and 55 patients followed a regorafenib-first or riFOLFOXIRI-first treatment strategy, respectively. At baseline, patient characteristics were similar between the groups, except for younger age in the riFOLFOXIRI-first group. The regorafenib-first group had better overall survival (13.8 vs. 10.7 mo, P=0.038), whereas patients in the riFOLFOXIRI-first group had a better partial response rate (P=0.005) but a higher rate of discontinuation due to adverse effects (P=0.004) and cross-over to regorafenib (P<0.001). Thus, no significant difference was observed in progression-free survival (regorafenib-first strategy: 3.17 mo; riFOLFOXIRI-first strategy: 4.97 mo; P=0.624). Regorafenib-first strategy, sex, and pathology were identified as independent prognostic factors. Subgroup analysis indicated that younger age, better performance status, stage IV disease, and mutant RAS gene favored the regorafenib-first strategy. CONCLUSION: Treatment with regorafenib-first followed by riFOLFOXIRI resulted in better overall survival when given as late-line treatment for patients with refractory mCRC.