Clinical outcomes of carbapenem-resistant gram-negative bacterial bloodstream infection in patients with end-stage renal disease in intensive care units: a multicenter retrospective observational study.

BACKGROUND: Carbapenem-resistant gram-negative bacteria (CRGNB) present a considerable global threat due to their challenging treatment and increased mortality rates, with bloodstream infection (BSI) having the highest mortality rate. Patients with end-stage renal disease (ESRD) undergoing renal replacement therapy (RRT) face an increased risk of BSI. Limited data are available regarding the prognosis and treatment outcomes of CRGNB-BSI in patients with ESRD in intensive care units (ICUs). METHODS: This multi-center retrospective observational study included a total of 149 ICU patients with ESRD and CRGNB-BSI in Taiwan from January 2015 to December 2019. Clinical and microbiological outcomes were assessed, and multivariable regression analysis was used to evaluate the independent risk factors for day-28 mortality and the impact of antimicrobial therapy regimen on treatment outcomes. RESULTS: Among the 149 patients, a total of 127 patients (85.2%) acquired BSI in the ICU, with catheter-related infections (47.7%) and pneumonia (32.2%) being the most common etiologies. Acinetobacter baumannii (49.0%) and Klebsiella pneumoniae (31.5%) were the most frequently isolated pathogens. The day-28 mortality rate from BSI onset was 52.3%, and in-hospital mortality was 73.2%, with survivors experiencing prolonged hospital stays. A higher Sequential Organ Failure Assessment (SOFA) score (adjusted hazards ratio [aHR], 1.25; 95% confidence interval [CI] 1.17-1.35) and shock status (aHR, 2.12; 95% CI 1.14-3.94) independently predicted day-28 mortality. Colistin-based therapy reduced day-28 mortality in patients with shock, a SOFA score of ≥ 13, and Acinetobacter baumannii-related BSI. CONCLUSIONS: CRGNB-BSI led to high mortality in critically ill patients with ESRD. Day-28 mortality was independently predicted by a higher SOFA score and shock status. In patients with higher disease severity and Acinetobacter baumannii-related BSI, colistin-based therapy improved treatment outcomes.

The impact and risk factors for developing pneumogenic bacteremia in carbapenem-resistant Acinetobacter baumannii nosocomial pneumonia in the intensive care unit: A multicenter retrospective study.

OBJECTIVES: This study analyzed the risk and impact of developing pneumogenic bacteremia in patients with CRAB nosocomial pneumonia in ICU. METHODS: This is multicenter retrospective study. Clinical outcomes were compared between bacteremia and non-bacteremia group, and the risk factors for mortality and developing pneumogenic CRAB bacteremia were analyzed. RESULTS: After patient recruitment, 164 cases were in the bacteremia group, and 519 cases were in the non-bacteremia group. The bacteremia group had 22.4 percentage of increase in-hospital mortality than the non-bacteremia group (68.3% vs 45.9%, P < 0.001). Multivariate analysis showed bacteremia was an independent risk factor for in-hospital mortality (aHR = 2.399, P < 0.001). A long time-interval between ICU admission and pneumonia onset was an independent risk factor for developing bacteremia (aOR = 1.040, P = < 0.001). Spearman's rank correlation analysis indicated a high correlation between the days from ICU admission to pneumonia onset and the days of ventilator use before pneumonia onset (correlation coefficient (ρ) = 0.777). CONCLUSIONS: In patients with CRAB nosocomial pneumonia, bacteremia increased the in-hospital mortality, and a longer interval from ICU admission to pneumonia onset was an independent risk factor for developing bacteremia, which was highly associated with the use of mechanical ventilation.

Combined Immunotherapy and Tyrosine Kinase Inhibitor Treatment for Metastatic Renal Cell Carcinoma With Unknown Primary Origin: A Report of Two Cases and Literature Review.

BACKGROUND/AIM: Renal cell carcinoma (RCC) of unknown primary origin is rarely identified and accounts for only 5% of cancers of unknown primary origin (CUP). The disease prognosis is typically poor because of no standard and effective therapy. Our review indicated that 23 cases have been reported and treated with conventional chemotherapy or tyrosine-kinase inhibitors alone; accordingly, most patients showed partial response or progression diseases with short survival time. CASE REPORT: Herein, we present two cases of metastatic RCC of unknown primary origin. One case was papillary type and the other was clear cell type. According to the recent clinical trials in patients with metastatic RCC, a combination of immunotherapy and tyrosine-kinase inhibitors exhibited better response than conventional therapy or tyrosine-kinase inhibitors alone. Both present cases accepted a combination treatment with immunotherapy and tyrosine-kinase inhibitor and showed stable diseases. The radiological progression-free time for the case with metastatic papillary RCC was 5 months, and that with clear cell RCC was 6 months until now. CONCLUSION: The combination of immunotherapy and tyrosine-kinase inhibitors is at least as effective as a tyrosine-kinase inhibitor alone, and superior to conventional chemotherapy for treating metastatic RCC of unknown primary origin.

Salvage boron neutron capture therapy for pediatric patients with recurrent diffuse midline glioma.

PURPOSE: Pediatric diffuse malignant glioma located in the brainstem was officially named "diffuse midline glioma" (DMG) by the World Health Organization in 2016. For this disease, radical surgery is not beneficial, and the only major treatment strategy is radiotherapy. However, the dose limitations to brainstem tissue mean that treatment by radiotherapy can only control and not eradicate the tumors, and there is no effective treatment for recurrence, resulting in short overall survival of 6-12 months. This paper reports our experience with boron neutron capture therapy (BNCT), a new treatment process, and its efficacy in treating children with recurrent DMG. METHODS: From September 2019 to July 2022, we treated 6 children affected by recurrent DMG. With the collaboration of Taipei Veteran General Hospital (TVGH) and National Tsing-Hua University (NTHU), each patient received two sessions of BNCT within 1 month. RESULTS: Among the six patients, three showed partial response and the rest had stable disease after the treatment. The overall survival and recurrence-free survival duration after treatment were 6.39 and 4.35 months, respectively. None of the patients developed severe side effects, and only one patient developed brain necrosis, which was most likely resulted from previous hypofractionated radiotherapy received. CONCLUSION: BNCT elicited sufficient tumor response with low normal tissue toxicity; it may benefit vulnerable pediatric patients with DMG.

Prostate Cancer after Percutaneous Arterial Embolization of the Prostate: A Case Report.

We report a patient with prostate cancer found 2 years after percutaneous arterial embolization (PAE) of the prostate with a rapid increase in prostate specific antigen (PSA) 3 months later, even though the initial result was low. He did not consult a urologist during or after PAE until acute urinary retention developed. The clinical stage was cT2cN1M1b with Gleason grade 5 + 5 = 10. An increase in PSA a short interval after PAE may suggest the presence of prostate cancer. We suggest that patients undergoing PAE should consult a urologist, and that PSA levels should be checked every 3 months in the first year after PSA.

Compassionate Treatment of Brainstem Tumors with Boron Neutron Capture Therapy: A Case Series.

Brainstem tumors are heterogenous and cancerous glioma tumors arising from the midbrain, pons, and the medulla that are relatively common in children, accounting for 10% to 20% of all pediatric brain tumors. However, the prognosis of aggressive brainstem gliomas remains extremely poor despite aggressive treatment with chemotherapy and radiotherapy. That means there are many life-threatening patients who have exhausted all available treatment options and are beginning to face end-of-life stage. Therefore, the unique properties of highly selective heavy particle irradiation with boron neutron capture therapy (BNCT) may be well suited to prolong the lives of patients with end-stage brainstem gliomas. Herein, we report a case series of life-threatening patients with end-stage brainstem glioma who eligible for Emergency and Compassionate Use, in whom we performed a scheduled two fractions of salvage BNCT strategy with low treatment dosage each time. No patients experienced acute or late adverse events related to BNCT. There were 3 patients who relapsed after two fractionated BNCT treatment, characterized by younger age, lower T/N ratio, and receiving lower treatment dose. Therefore, two fractionated low-dose BNCT may be a promising treatment for end-stage brainstem tumors. For younger patients with low T/N ratios, more fractionated low-dose BNCT should be considered.

SARS-CoV-2 E484K Mutation Narrative Review: Epidemiology, Immune Escape, Clinical Implications, and Future Considerations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly over the world and claimed million lives. The virus evolves constantly, and a swarm of mutants is a now major concern globally. Distinct variants could have independently converged on same mutation, despite being detected in different geographic regions, which suggested it could confer an evolutionary advantage. E484K has rapidly emerged and has frequently been detected in several SARS-CoV-2 variants of concern. In this study, we review the epidemiology and impact of E484K, its effects on neutralizing effect of several monoclonal antibodies, convalescent plasma, and post-vaccine sera.

COVID-19 Screening for Hospitalized Patients: The Role of Expanded Hospital Surveillance in a Low Prevalence Setting.

PURPOSE: The COVID-19 pandemic poses a serious threat to healthcare workers and hospitalized patients. Early detection of COVID-19 cases is essential to control the spread in healthcare facilities. However, real-world data on the screening criteria for hospitalized patients remain scarce. We aimed to explore whether patients with negative results of pre-hospital screening for COVID-19 should be rescreened after admission in a low-prevalence (less than 3% of the world average) setting. PATIENTS AND METHODS: We retrospectively included patients in central Taiwan who were negative at the first screening but were newly diagnosed with pneumonia or had a body temperature above 38 degrees Celsius during their hospitalization. Each patient might be included as an eligible case several times, and the proportions of cases who were rescreened for COVID-19 and those diagnosed with COVID-19 were calculated. A logistic regression model was constructed to identify factors associated with rescreening. Reverse transcription-polymerase chain reaction tests were used to confirm the diagnosis of COVID-19. RESULTS: A total of 3549 cases eligible for COVID-19 rescreening were included. There were 242 cases (6.8%) who received rescreening. In the multivariable analysis, cases aged 75 years or older, those with potential exposure to SARS-CoV-2, or patients visiting specific departments, such as the Cardiovascular Center and Department of Neurology, were more likely to be rescreened. None was diagnosed with COVID-19 after rescreening. There was no known cluster infection outbreak in the hospital or in the local community during the study period and in the following two months. CONCLUSION: In Taiwan, a country with a low COVID-19 prevalence, it was deemed safe to rescreen only high-risk hospitalized patients. This strategy was effective and reduced unnecessary costs.

Foveal Microvascular Integrity Association With Anti-VEGF Treatment Response for Diabetic Macular Edema.

Purpose: To investigate the association between foveal microvascular integrity and anti-vascular endothelial growth factor (VEGF) treatment response for diabetic macular edema (DME). Methods: This retrospective study enrolled 58 eyes (from 45 patients) with DME. Treatment strategy was three to five monthly anti-VEGF injections followed by a PRN protocol. Treatment with an intravitreal corticosteroid would be considered for persistent DME after five consecutive anti-VEGF injections. Eyes achieving a treatment-free interval ≥ four months within two years were classified into the good clinical course group (group 1). Eyes with frequent recurrent edema (treatment-free interval < four months) or requiring an intravitreal corticosteroid within two years were classified into the suboptimal clinical course group (group 2). Foveal microvascular integrity was evaluated by two continuous variables, that is, vessel density (%) within a width of 300 µm around the foveal avascular zone (FD-300) on optical coherence tomography angiography (OCTA) and perifoveal leakage (area %) on fluorescein angiography (FA). Results: There were 37 eyes in group 1 and 21 eyes in group 2. FD-300 (odds ratio 0.733, 95% CI 0.620-0.867, P < 0.001) and perifoveal leakage (odds ratio 1.064, 95% CI 1.007-1.124, P = 0.027) were significantly associated with suboptimal clinical course. Area under curve (AUC) was 0.820 for FD-300 and 0.723 for perifoveal leakage in predicting clinical course. FD-300 was negatively correlated with perifoveal leakage (coefficient = -0.325, P = 0.014). Conclusions: Compromised foveal microvascular integrity, represented by lower FD-300 and more severe perifoveal fluorescein leakage, was associated with suboptimal clinical course in anti-VEGF treatment for DME. A negative correlation between FD-300 and perifoveal leakage existed.

Shewanella algae and Morganella morganii Coinfection in Cobra-Bite Wounds: A Genomic Analysis.

Naja atra bites cause severe soft tissue injury and are prone to wound infections. The pathogens of Naja atra bite-wound infections are highly variable in different geographical regions. Here, we report the first coinfection with Shewanella algae and Morganella morganii from a Naja atra bite wound with resistome analysis using whole genome sequencing.

Clinical manifestation of multiple wasp stings with details of whole transcriptome analysis: Two case reports.

INTRODUCTION: Multiple wasp stings is an emergency result from systemic reactions to the toxin with a wide range of manifestations, and we presented 2 patients with distinct clinical and transcriptomic findings. PATIENT CONCERNS: Two patients without systemic disease presented with nearly 90 painful papules after attacked by a swarm of wasps (Vespa basalis). DIAGNOSIS: Patient 1 was a 44-year-old healthy male whose clinical manifestations mainly comprised hemolysis, hepatic injury, rhabdomyolysis, and acute kidney injury. Patient 2 was a 49-year-old healthy female who presented with severe acute respiratory distress syndrome (ARDS) in addition to certain clinical manifestations that were also found in patient 1. We used ribo- nucleic acid sequencing (RNA-Seq) to characterize the inflammatory responses of 2 patients with distinct clinical manifestations after multiple wasp stings. INTERVENTIONS: Both 2 patients received 5 sessions of plasmapheresis, and patient-1 further received mechanical ventilation for 8 days as well as 8 sessions of hemodialysis until day 17. OUTCOMES: Both patients recovered uneventfully after the aforementioned management. We used RNA-Seq to demonstrate a largely regulated neutrophil-predominated immune response in patient 1. In patient 2, we found a profound neutrophilc response on week 1 and a robust neutrophilic as well as pro-inflammatory responses on week 2. Furthermore, we found increased expression of signals that were associated with renal system process on week 2. CONCLUSION: In conclusion, we report 2 patients who manifested with shared and distinct presentations after an attack by the same swarm of wasps. Both patients had hemolysis, rhabdomyolysis, hepatic injury and acute kidney injury, and 1 patient had ARDS. The whole transcriptomic analyses were consistent with the distinct clinical manifestation, and these results suggest the potential of RNA-Sequencing to disentangle complex inflammatory responses in patients with multiple wasp stings. Plasmapheresis and corticosteroid were administered to both patients and case 2 also underwent 8 sessions of hemodialysis.

Abiraterone and enzalutamide had different adverse effects on the cardiovascular system: a systematic review with pairwise and network meta-analyses.

BACKGROUND: Abiraterone and enzalutamide may increase the risk of cardiovascular events in patients with castration-resistant prostate cancer (CRPC). METHODS: A comprehensive literature search was performed using a combination of keywords related to "abiraterone," "enzalutamide," "prostate cancer," and "adverse events." Phase II-IV randomized controlled trials (RCTs) on abiraterone or enzalutamide for patients with nonmetastatic or metastatic CRPC were included. Outcome measures included (1) any grade cardiac disorder, (2) severe grade cardiac disorder, (3) any grade hypertension, and (4) severe grade hypertension, as defined by the Common Terminology Criteria for Adverse Events. Pairwise meta-analysis and Bayesian network meta-analyses were performed to investigate the risk ratios (RRs) of abiraterone and enzalutamide. Surface under cumulative ranking curves (SUCRAs) and cumulative ranking probability plots based on the probability of developing cardiac disorders or hypertension were presented. RESULTS: A total of 7103 patients from seven RCTs were included. Upon pairwise meta-analysis, abiraterone was associated with increased risks of any grade (RR = 1.34, 95% confidence interval (CI) = 1.05-1.73) and severe grade cardiac disorders (RR = 1.71, 95% CI = 1.16-2.53); enzalutamide was associated with increased risks of any grade (RR = 2.66, 95% CI = 1.93-3.66) and severe grade hypertension (RR = 2.79, 95% CI = 1.86-4.18). Based on the SUCRA rankings, abiraterone had a higher probability of cardiac disorders (84.84% for any grade and 85.12% for severe grade) than enzalutamide (62.83% for any grade and 50.76% for severe grade); whereas enzalutamide had a higher probability of hypertension (99.43% for any grade and 89.71% for severe grade) than abiraterone (49.08% for any grade and 49.37% for severe grade). CONCLUSIONS: Abiraterone and enzalutamide had different adverse effects on the cardiovascular system. We should take this into consideration when we are deciding on the choice of novel hormonal agents for patients with CRPC.

Femtosecond laser-assisted cataract surgery in a patient with traumatic cataract and corneal opacity after LASIK: a case report.

BACKGROUND: Femtosecond laser-assisted cataract surgery (FLACS) has been reported to reduce phacoemulsification time and energy compared to the manual phacoemulsification technique. This technique has been used in several complex cases such as zonular weakness, subluxated lens and traumatic cataracts because it causes less damage to weakened zonules. However, corneal opacity is considered a relative contraindication to FLACS, as it may interfere with laser beam delivery, thus causing unpredictable capsulorhexis and lens fragmentation/liquefaction. CASE PRESENTATION: We present here a case with traumatic cataract and corneal opacity after laser-assisted in situ keratomileusis (LASIK). The patient was successfully treated using FLACS, capsular tension ring and intraocular lens (IOL) implantation. Posterior capsule rupture and vitreous loss were noted during the operation. However, the intraocular lens was successfully captured because of a complete capsulorhexis performed by FLACS. CONCLUSION: This case report demonstrates that FLACS is a useful tool in selected patients with concurrent corneal opacity and traumatic cataract.

2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan, China.

We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.

Mirabegron is alternative to antimuscarinic agents for overactive bladder without higher risk in hypertension: a systematic review and meta-analysis.

PURPOSE: Mirabegron, a ß3-adrenoceptor agonist, was approved for overactive bladder (OAB), but worsened hypertension was a potential risk based on its mechanism of action. Besides, head to head comparisons were limited between mirabegron and antimuscarinic agents, the prior first-line pharmacotherapy of OAB. In this regard, we performed a systematic review and meta-analysis to compare their efficacy as well as safety, especially in blood pressure changes. MATERIALS AND METHODS: Literature search was conducted in PubMed, Medline and seven randomized clinical trial (RCT) register databases of WHO, EU, USA, Taiwan, China, Japan and Cochrane. Completed RCTs for OAB with mirabegron and antimuscarinics were identified and the last comprehensive search was run in August 2017. Cochrane risk of bias tool was used to assess the potential bias, and RevMan5 software was performed for meta-analysis. RESULTS: Seven eligible RCTs (four for mirabegron vs. tolterodine and three for mirabegron vs. solifenacin) were included and demonstrated similar efficacy in micturitions, incontinence, and nocturia between mirabegron and antimuscarinics. In hypertension issue, no statistical differences were showed in risk ratio (RR) of hypertension events, change of blood pressure from baseline and change of blood pressure from placebo for all participants. On the other hand, RR of dry mouth was significantly lower in mirabegron users. CONCLUSIONS: Mirabegron was not inferior effective in improving OAB symptoms compared with antimuscarinic agents. In addition, mirabegron presented lower incidence of dry mouth and not higher risk for hypertension. Therefore, mirabegron has potential to be an alternative therapeutic option for OAB control.

The percentage of resected and ischemic volume determined by a geometric model is a significant predictor of renal functional change after partial nephrectomy

ABSTRACT Purpose The percentage of parenchyma preserved plays a predominant role in predicting renal function after partial nephrectomy (PN). Currently there is no standard method to estimate preserved renal parenchyma. In this study we propose a formula of the percentage of resected and ischemic volume (PRAIV) determined by a geometric model and evaluate the relationships between renal functional change and PRAIV as well as other clinical parameters. Materials and Methods We identified 71 patients who underwent open PN between January 2004 and April 2014. Assuming the kidney to be an ellipsoid with bilaterally equal volume and tumor to be a sphere, we calculated PRAIV by integral calculus. Nadir estimated glomerular filtration rate (eGFR) between postoperative 3 and 12 months were recorded. The correlation between percent eGFR reduction, PRAIV, and other clinical parameters were examined. Results On univariate analysis, age (p=0.03), depth of tumor invasion (p=0.004), C index (p=0.003), RAIV (p=0.04), and PRAIV (p<0.001) were correlated with percent reduction of eGFR. However, only age (p=0.007) and PRAIV (p<0.001) were significantly correlated with percent reduction of eGFR on multivariate analysis. Depicting these values along the regression line, we found R2 was 0.194 and 0.073 for PRAIV and age, respectively. Conclusions PRAIV determined by a geometric model is a significant predictor of renal functional change after PN. Using PRAIV, we can estimate percent eGFR reduction preoperatively for better patient consultation and surgical planning.

The percentage of resected and ischemic volume determined by a geometric model is a significant predictor of renal functional change after partial nephrectomy.

PURPOSE: The percentage of parenchyma preserved plays a predominant role in predicting renal function after partial nephrectomy (PN). Currently there is no standard method to estimate preserved renal parenchyma. In this study we propose a formula of the percentage of resected and ischemic volume (PRAIV) determined by a geometric model and evaluate the relationships between renal functional change and PRAIV as well as other clinical parameters. MATERIALS AND METHODS: We identified 71 patients who underwent open PN between January 2004 and April 2014. Assuming the kidney to be an ellipsoid with bilaterally equal volume and tumor to be a sphere, we calculated PRAIV by integral calculus. Nadir estimated glomerular filtration rate (eGFR) between postoperative 3 and 12 months were recorded. The correlation between percent eGFR reduction, PRAIV, and other clinical parameters were examined. RESULTS: On univariate analysis, age (p=0.03), depth of tumor invasion (p=0.004), C index (p=0.003), RAIV (p=0.04), and PRAIV (p<0.001) were correlated with percent reduction of eGFR. However, only age (p=0.007) and PRAIV (p<0.001) were significantly correlated with percent reduction of eGFR on multivariate analysis. Depicting these values along the regression line, we found R2 was 0.194 and 0.073 for PRAIV and age, respectively. CONCLUSIONS: PRAIV determined by a geometric model is a significant predictor of renal functional change after PN. Using PRAIV, we can estimate percent eGFR reduction preoperatively for better patient consultation and surgical planning.

RNA editing and drug discovery for cancer therapy.

RNA editing is vital to provide the RNA and protein complexity to regulate the gene expression. Correct RNA editing maintains the cell function and organism development. Imbalance of the RNA editing machinery may lead to diseases and cancers. Recently, RNA editing has been recognized as a target for drug discovery although few studies targeting RNA editing for disease and cancer therapy were reported in the field of natural products. Therefore, RNA editing may be a potential target for therapeutic natural products. In this review, we provide a literature overview of the biological functions of RNA editing on gene expression, diseases, cancers, and drugs. The bioinformatics resources of RNA editing were also summarized.

Modeling and analysis of coagulated liver tissue and its interaction with a scalpel blade.

Radiofrequency-assisted methods have been used in hepatectomy--the resection process of removing liver tissue which encapsulates the tumor from the liver organ. A prototype was built to enable smooth surgical transition between radiofrequency ablation and liver resection. There is a lack of literature on mechanical properties of radiofrequency-ablated liver tissue and the tool-tissue interaction during cutting. This led to our study on coagulated tissue mechanical properties and modeling of its dynamic interaction with a scalpel blade. A novel mechanical model was proposed to mimic the mechanical behavior of radiofrequency-ablated liver tissue. The model is able to account for the viscoelastic behavior of the ablated tissue in both compression and relaxation tests. Experiments were performed to validate the proposed model. In addition, a knife blade-tissue interaction model is proposed to demonstrate the potential of integrating the proposed model for application in device design.

Integrated ablation and division device for liver resection.

BACKGROUND: Intraoperative blood loss during liver resection may be minimized by ablating the liver parenchyma using radiofrequency (RF) energy. However, it is difficult to estimate the depth of the avascular plane and more RF energy than necessary may be inadvertently used as a result of lack of feedback. METHODS: Laparoscopic liver resection was performed on a live porcine model to determine the feasibility and applicability of a model which integrates ablation and division in a single device. RESULTS: Liver resection was uncomplicated with minimal bleeding. The integration of the ablation and division mechanism resolved the difficulty of estimating the depth of the avascular plane after coagulation. The real-time feedback mechanism minimized liver damage by eliminating the application of unnecessary RF. CONCLUSIONS: The proposed model is functionally acceptable and represents a possible method of determining the depth of the avascular plane and the amount of RF energy required during liver resection.