Genomic characterization of Staphylococcus aureus isolated from patients admitted to intensive care units of a tertiary care hospital: epidemiological risk of nasal carriage of virulent clone during admission.

We conducted a molecular epidemiological study of Staphylococcus aureus using whole-genome sequence data and clinical data of isolates from nasal swabs of patients admitted to the intensive care unit (ICU) of Hiroshima University hospital. The relationship between isolate genotypes and virulence factors, particularly for isolates that caused infectious diseases during ICU admission was compared with those that did not. The nasal carriage rates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) in patients admitted to the ICU were 7.0% and 20.1%, respectively. The carriage rate of community-acquired (CA)-MRSA was 2.3%, accounting for 32.8% of all MRSA isolates. Whole-genome sequencing analysis of the MRSA isolates indicated that most, including CA-MRSA and healthcare-associated (HA)-MRSA, belonged to clonal complex (CC) 8 [sequence type (ST) 8] and SCCmec type IV. Furthermore, results for three disease foci (pneumonia, skin and soft tissue infection, and deep abscess) and the assessment of virulence factor genes associated with disease conditions [bacteremia, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC), and septic shock] suggested that nasal colonization of S. aureus clones could represent a risk for patients within the ICU. Particularly, MRSA/J and MSSA/J may be more likely to cause deep abscess infection; ST764 may cause ventilation-associated pneumonia, hospital-acquired pneumonia and subsequent bacteremia, and ARDS, and tst-1-positive isolates may cause DIC onset.IMPORTANCENasal colonization of MRSA in patients admitted to the intensive care unit (ICU) may predict the development of MRSA infections. However, no bacteriological data are available to perform risk assessments for Staphylococcus aureus infection onset. In this single-center 2-year genomic surveillance study, we analyzed all S. aureus isolates from nasal swabs of patients admitted to the ICU and those from the blood or lesions of in-patients who developed infectious diseases in the ICU. Furthermore, we identified the virulent clones responsible for causing infectious diseases in the ICU. Herein, we report several virulent clones present in the nares that are predictive of invasive infections. This information may facilitate the design of preemptive strategies to identify and eradicate virulent MRSA strains, reducing nosocomial infections within the ICU.

Association between changes in disease severity and physical function after surviving a critical illness: A multicentre retrospective observational study.

BACKGROUND: Whilst disease severity can significantly impact functional outcomes, the ability to predict the scale of this impact has not been consistent. AIM: We aimed to investigate whether changes in disease severity within the first 48 h of ICU admission are more strongly associated with physical dysfunction than a single-time assessment of disease severity at ICU admission. METHODS: A multicentre retrospective study in seven tertiary ICUs in Japan, including all consecutive adult ICU patients (>48 h ICU stay) between September 2019 and February 2020. The primary outcome was physical function defined as the Barthel Index, which is an ordinal scale (0-100: larger indicates better function) to measure physical independence and performance. The association between Barthel Index score at hospital discharge and the Sequential Organ Failure Assessment (SOFA) scores, measured at ICU admission, the highest recorded score within 48 h of ICU admission, and the level of change between these two timepoints were investigated in multivariable analysis. RESULTS: A total of 199 patients were included. Median SOFA score at ICU admission and the highest recorded score within the first 48 h were 6 (interquartile range: 5-10) and 8 (interquartile range: 6-11), respectively. A quarter of patients had a Barthel Index score of 60 or less at hospital discharge. The highest SOFA score within 48 h of ICU admission and the level of change in SOFA scores between ICU admission and the highest recorded score within 48 h were significantly associated with lower Barthel Index scores at hospital discharge. No significant association was identified with regard to Barthel Index scores and SOFA score at ICU admission. An increase in SOFA score of 1 or more within the first 48 h of ICU admission was the threshold to predict a Barthel Index score of 60 or less at hospital discharge. Larger changes in SOFA scores over the first 48 h of ICU admission were also significantly associated with smaller changes in Barthel Index scores from ICU discharge to hospital discharge. CONCLUSIONS: The level of change in SOFA score between ICU admission and the highest recorded score within the first 48 h of ICU stay can more accurately predict the presence of physical dysfunction at hospital discharge than a single-time assessment of disease severity at ICU admission. The larger worsening in SOFA potentially indicates lower recovery after a critical illness.

External validation of the rCAST for patients after in-hospital cardiac arrest: a multicenter retrospective observational study.

No established predictive or risk classification tool exists for the neurological outcomes of post-cardiac arrest syndrome (PCAS) in patients with in-hospital cardiac arrest (IHCA). This study aimed to investigate whether the revised post-cardiac arrest syndrome for therapeutic hypothermia score (rCAST), which was developed to estimate the prognosis of PCAS patients with out-of-hospital cardiac arrest (OHCA), was applicable to patients with IHCA. A retrospective, multicenter observational study of 140 consecutive adult IHCA patients admitted to three intensive care units. The area under the receiver operating characteristic curves (AUCs) of the rCAST for poor neurological outcome and mortality at 30 days were 0.88 (0.82-0.93) and 0.83 (0.76-0.89), respectively. The sensitivity and specificity of the risk classification according to rCAST for poor neurological outcomes were 0.90 (0.83-0.96) and 0.67 (0.55-0.79) for the low, 0.63 (0.54-0.74) and 0.67 (0.55-0.79) for the moderate, and 0.27 (0.17-0.37) and 1.00 (1.00-1.00) for the high-severity grades. All 22 patients classified with a high-severity grade showed poor neurological outcomes. The rCAST showed excellent predictive accuracy for neurological prognosis in patients with PCAS after IHCA. The rCAST may be useful as a risk classification tool for PCAS after IHCA.

Instruments to assess post-intensive care syndrome assessment: a scoping review and modified Delphi method study.

BACKGROUND: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors. METHODS: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important. RESULTS: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R. CONCLUSION: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families.

Japanese Clinical Practice Guidelines for Rehabilitation in Critically Ill Patients 2023 (J-ReCIP 2023).

Providing standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the "Evidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unit" to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions.

Predictive Accuracy of the ROX Index for Re-Intubation in Mechanically Ventilated Patients With COVID-19.

BACKGROUND: Several studies have suggested that high-flow nasal cannula (HFNC) is useful for respiratory support after extubation in subjects with COVID-19 pneumonia, whereas 18% subsequently needed to undergo re-intubation. This study aimed to evaluate whether the breathing frequency (f)-ratio of oxygen saturation (ROX) index, which has been shown to be useful for predicting future intubation, is also useful for re-intubation in subjects with COVID-19. METHODS: We retrospectively analyzed mechanically ventilated subjects with COVID-19 who underwent HFNC therapy after extubation at 4 participating hospitals between January 2020-May 2022. We evaluated the predictive accuracy of ROX at 0, 1, and 2 h for re-intubation until ICU discharge and compared the area under the receiver operating characteristic (ROC) curve of the ROX index with those of f and SpO2 /FIO2 . RESULTS: Among the 248 subjects with COVID-19 pneumonia, 44 who underwent HFNC therapy after extubation were included. A total of 32 subjects without re-intubation were classified into the HFNC success group, and 12 with re-intubation were classified into the failure group. The overall trend that the area under the ROC curve of the ROX index was greater than that of the f and SaO2 /FIO2 was observed, although there was no statistical significance at any time point. The ROX index at 0 h, at the cutoff point of < 7.44, showed a sensitivity and specificity of 0.42 and 0.97, respectively. A trend of positive correlation between the time until re-intubation and ROX index at each time point was observed. CONCLUSIONS: The ROX index in the early phase of HFNC therapy after extubation was useful for predicting re-intubation with high accuracy in mechanically ventilated subjects with COVID-19. Close observation for patients with < 7.44 ROX index just after extubation may be warranted because of their high risk for re-intubation.

GENETIC DELETION OF TRANSLOCATOR PROTEIN EXACERBATES POST-SEPSIS SYNDROME WITH ACTIVATION OF THE C1Q PATHWAY IN SEPTIC MOUSE MODEL.

ABSTRACT: Significant numbers of patients who survive sepsis exhibit psychiatric and cognitive impairments, termed post-sepsis syndrome. Understanding the underlying pathophysiology is essential to develop effective therapies. Translocator protein 18 kDa (TSPO) is a multifaceted mitochondrial protein implicated in inflammation, oxidative stress, and steroidogenesis in the central nervous system. Despite accumulated evidence demonstrating TSPO is a biomarker in psychiatric and neurodegenerative disorders, the role of this protein in post-sepsis syndrome remains elusive. The aim of this study was to investigate the role of TSPO in the long-term impairment of mouse behavior associated with psychiatric and cognitive impairments following sepsis induced by cecal ligation and puncture (CLP) surgery. Animals were divided into three groups: (i) wild type (WT) + sham, (ii) WT + CLP, and (iii) TSPO knock out + CLP. Survival rate and body weight change were assessed up to 17 days after surgeries. Then, we also assessed anxiety-like behavior, depression-like behavior, cognitive function, locomotor activity, and forelimb muscle strength in surviving mice by elevated plus maze, tail suspension test, y-maze, open field test, and grip strength test, respectively. Deletion of the TSPO gene led to high mortality and prolonged weight loss and exacerbated anxiety-like and depressive-like behavior with cognitive impairment 17 days after, but not before, CLP surgery. RNA-seq analysis of the hippocampus revealed the upregulation of genes (C1qb, C1qc, and Tyrobp) in C1q complement pathways correlated significantly with anxiety-like behavior that appeared long after CLP surgery. The expressions of these genes predicted other behavioral traits, including depressive-like behavior in the tail suspension test and grip power impairment, supporting the role of the C1q pathway in post-sepsis syndrome. Because the C1q pathway has recently attracted interest as a tag for pathological synaptic elimination, the current study suggests the C1q pathway is involved in the psychiatric and cognitive impairments observed in post-sepsis syndrome.

Quantification of respiratory sounds by a continuous monitoring system can be used to predict complications after extubation: a pilot study.

To show that quantification of abnormal respiratory sounds by our developed device is useful for predicting respiratory failure and airway problems after extubation. A respiratory sound monitoring system was used to collect respiratory sounds in patients undergoing extubation. The recorded respiratory sounds were subsequently analyzed. We defined the composite poor outcome as requiring any of following medical interventions within 48 h as defined below. This composite outcome includes reintubation, surgical airway management, insertion of airway devices, unscheduled use of noninvasive ventilation or high-flow nasal cannula, unscheduled use of inhaled medications, suctioning of sputum by bronchoscopy and unscheduled imaging studies. The quantitative values (QV) for each abnormal respiratory sound and inspiratory sound volume were compared between composite outcome groups and non-outcome groups. Fifty-seven patients were included in this study. The composite outcome occurred in 18 patients. For neck sounds, the QVs of stridor and rhonchi were significantly higher in the outcome group vs the non-outcome group. For anterior thoracic sounds, the QVs of wheezes, rhonchi, and coarse crackles were significantly higher in the outcome group vs the non-outcome group. For bilateral lateral thoracic sounds, the QV of fine crackles was significantly higher in the outcome group vs the non-outcome group. Cervical inspiratory sounds volume (average of five breaths) immediately after extubation was significantly louder in the outcome group vs non-outcome group (63.3 dB vs 54.3 dB, respectively; p < 0.001). Quantification of abnormal respiratory sounds and respiratory volume may predict respiratory failure and airway problems after extubation.

Regional respiratory sound abnormalities in pneumothorax and pleural effusion detected via respiratory sound visualization and quantification: case report.

Assessment of respiratory sounds by auscultation with a conventional stethoscope is subjective. We developed a continuous monitoring and visualization system that enables objectively and quantitatively visualizing respiratory sounds. We herein present two cases in which the system showed regional differences in the respiratory sounds. We applied our novel continuous monitoring and visualization system to evaluate respiratory abnormalities in patients with acute chest disorders. Respiratory sounds were continuously recorded to assess regional changes in respiratory sound volumes. Because we used this system as a pilot study, the results were not shown in real time and were retrospectively analyzed. Case 1 An 89-year-old woman was admitted to our hospital for sudden-onset respiratory distress and hypoxia. Chest X-rays revealed left pneumothorax; thus, we drained the thorax. After confirming that the pneumothorax had improved, we attached the continuous monitoring and visualization system. Chest X-rays taken the next day showed exacerbation of the pneumothorax. Visual and quantitative findings showed a decreased respiratory volume in the left lung after 3 h. Case 2 A 94-year-old woman was admitted to our hospital for dyspnea. Chest X-rays showed a large amount of pleural effusion on the right side. The continuous monitoring and visualization system visually and quantitatively revealed a decreased respiratory volume in the lower right lung field compared with that in the lower left lung field. Our newly developed continuous monitoring and visualization system enabled quantitatively and visually detecting regional differences in respiratory sounds in patients with pneumothorax and pleural effusion.

Case Report: Emphysematous Pyelonephritis With a Congenital Giant Ureterocele.

A 14-year-old girl noticed malodorous urine and experienced left flank pain. The patient was presented to our hospital with gradually increasing pain. She had no underlying disease but had a history of pain on micturition for several days. Hematologic examination indicated low white blood cell and platelet counts and a high serum lactate level. Computed tomography showed that a part of the parenchyma of the left kidney had poor contrast and was deteriorated, with fluid and gas retention from the perirenal region to the retroperitoneal cavity. A left hydroureter and large ureterocele were observed in the bladder. She was diagnosed with emphysematous pyelonephritis (EPN) with a giant congenital ureterocele. Vasopressors and blood transfusion failed to maintain normal circulatory dynamics, and an open left nephrectomy and transurethral ureterocele fenestration were performed. The excised outer portion of the left kidney was dissolved by the infection and replaced with blood clots and necrotic tissue. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identified the inflammatory, gas-producing bacteria Actinotignum schaalii, Peptoniphilus asaccharolyticus, and Actinomyces odontolyticus. Meropenem was administered for 4 days postoperatively and then de-escalated to sulbactam/ampicillin for another 10 days. The patient was discharged on day 17 of hospitalization, and the postoperative course remained favorable. EPN is extremely rare in pediatric patients, and it is believed that nephrectomy is sometimes necessary if the patient does not have normal circulatory dynamics despite the use of catecholamines.

TAFRO Syndrome in a Kidney Transplant Recipient That Was Diagnosed on Autopsy: A Case Report.

A 57-year-old man who received a kidney transplant 4 years previously owing to unknown underlying disease presented with thrombocytopenia and fever. Hepatosplenomegaly and lymphadenopathy were observed, and development of prominent anasarca and worsening of renal function yielded the diagnosis of TAFRO syndrome. He was treated with high-dose steroids and plasmapheresis, and a thrombopoietin receptor agonist was administered for refractory thrombocytopenia. However, his general condition worsened, and he died on day 92. Histopathological analysis of a kidney autopsy specimen showed thrombotic microangiopathy characterized by glomerular endothelial swelling, mesangiolysis, and double contours of the glomerular capillary walls. His bone marrow showed megakaryocytic hyperplasia with mild reticulin fibrosis. Interestingly, these clinical and pathological features were remarkably similar to those the patient demonstrated before the kidney transplant, suggesting the recurrence of TAFRO syndrome. TAFRO syndrome is a rare systemic disorder whose concept has recently been established, but information on its long-term outcome is scarce. To our knowledge, this is the first case of TAFRO syndrome developing in a kidney transplant recipient, which suggests that disease recurrence occurs many years after the kidney transplant.

Risk Factors of Patient-Related Safety Events during Active Mobilization for Intubated Patients in Intensive Care Units-A Multi-Center Retrospective Observational Study.

The aim of this study is to clarify the incidence and risk factors of patient-related safety events (PSE) in situations limited to intubated patients in which active mobilization, such as sitting on the edge of the bed/standing/walking, was carried out. A multi-center retrospective observational study was conducted at nine hospitals between January 2017 and March 2018. The safety profiles and PSE of 87 patients were analyzed. PSE occurred in 10 out of 87 patients (11.5%) and 13 out of 198 sessions (6.6%). The types of PSE that occurred were hypotension (8, 62%), heart rate instability (3, 23%), and desaturation (2, 15%). Circulation-related events occurred in 85% of overall cases. No accidents, such as line/tube removal or falls, were observed. The highest incidence of PSE was observed during the mobilization level of standing (8 out of 39 sessions, 20.5%). The occurrence of PSE correlated with the highest activity level under logistic regression analysis. Close vigilance is required for intubated patients during active mobilization in the standing position with regard to circulatory dynamics.

Prevalence of rapid response systems in small hospitals: A questionnaire survey.

ABSTRACT: The rapid response system (RRS) was introduced for early stage intervention in patients with deteriorating clinical conditions. Responses to unexpected in-hospital patient emergencies varied among hospitals. This study was conducted to understand the prevalence of RRS in smaller hospitals and to identify the need for improvements in the responses to in-hospital emergencies.A questionnaire survey of 971 acute-care hospitals in western Japan was conducted from May to June 2019 on types of in-hospital emergency response for patients in cardiac arrest (e.g., medical emergency teams [METs]), before obvious deterioration (e.g., rapid response teams [RRTs]), and areas for improvement.We received 149 responses, including those from 56 smaller hospitals (≤200 beds), which provided fewer responses than other hospitals. Response systems for cardiac arrest were used for at least a limited number of hours in 129 hospitals (87%). The absence of RRS was significantly more frequent in smaller hospitals than in larger hospitals (13/56, 23% vs 1/60, 2%; P < .01). METs and RRTs operated in 17 (11%) and 15 (10%) hospitals, respectively, and the operation rate for RRTs was significantly lower in smaller hospitals than in larger hospitals (1/56, 2% vs 12/60, 20%; P < .01). Respondents identified the need for education and more medical staff and supervisors; data collection or involvement of the medical safety management sector was ranked low.The prevalence of RRS or predetermined responses before obvious patient deterioration was ≤10% in small hospitals. Specific education and appointment of supervisors could support RRS in small hospitals.

Occurrence and incidence rate of peripheral intravascular catheter-related phlebitis and complications in critically ill patients: a prospective cohort study (AMOR-VENUS study).

BACKGROUND: The lack of precise information on the epidemiology of peripheral intravascular catheter (PIVC)-related phlebitis and complications in critically ill patients results in the absence of appropriate preventive measures. Therefore, we aimed to describe the epidemiology of the use of PIVCs and the incidence/occurrence of phlebitis and complications in the intensive care unit (ICU). METHODS: This prospective multicenter cohort study was conducted in 23 ICUs in Japan. All consecutive patients aged ≥ 18 years admitted to the ICU were enrolled. PIVCs inserted prior to ICU admission and those newly inserted after ICU admission were included in the analysis. Characteristics of the ICU, patients, and PIVCs were recorded. The primary and secondary outcomes were the occurrence and incidence rate of PIVC-related phlebitis and complications (catheter-related blood stream infection [CRBSI] and catheter failure) during the ICU stay. RESULTS: We included 2741 patients and 7118 PIVCs, of which 48.2% were inserted in the ICU. PIVC-related phlebitis occurred in 7.5% (95% confidence interval [CI] 6.9-8.2%) of catheters (3.3 cases / 100 catheter-days) and 12.9% (95% CI 11.7-14.2%) of patients (6.3 cases / 100 catheter-days). Most PIVCs were removed immediately after diagnosis of phlebitis (71.9%). Grade 1 was the most common phlebitis (72.6%), while grade 4 was the least common (1.5%). The incidence rate of CRBSI was 0.8% (95% CI 0.4-1.2%). In cases of catheter failure, the proportion and incidence rate per 100 intravenous catheter-days of catheter failure were 21% (95% CI 20.0-21.9%) and 9.1 (95% CI 8.7-10.0), respectively. CONCLUSION: PIVC-related phlebitis and complications were common in critically ill patients. The results suggest the importance of preventing PIVC-related complications, even in critically ill patients. TRIAL REGISTRATION: UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019 , July 1, 2017).

A case of light chain (AL) amyloidosis with heart failure, renal dysfunction, and heparin-induced thrombocytopenia successfully treated with peritoneal dialysis.

A 65-year-old woman was hospitalized for heart failure and pneumonia in a nearby hospital. She had been previously diagnosed as light chain (AL) amyloidosis and treated with melphalan plus dexamethasone (Mel-Dex), and lenalidomide plus dexamethasone (Len-Dex). She started treatment including antimicrobials and diuretics, but her renal function worsened progressively, and she was transferred to our hospital for nephrological care. She was treated with antimicrobials, noradrenaline, dobutamine, and continuous hemodiafiltration. Her general condition gradually stabilized, and she was switched to intermittent hemodialysis (HD). However, HD was discontinued due to intradialytic hypotension and the development of heparin-induced thrombocytopenia. Her renal replacement therapy was switched to peritoneal dialysis (PD), which enabled good volume control and stable cardiac function. She was discharged and is still in good condition, without serious complications and achieving a considerably better prognosis than was predicted. Our case suggests that PD is an effective modality for patients with AL amyloidosis with heart failure and renal dysfunction.

Prolonged versus intermittent ß-lactam antibiotics intravenous infusion strategy in sepsis or septic shock patients: a systematic review with meta-analysis and trial sequential analysis of randomized trials.

BACKGROUND: The prolonged ß-lactam infusion strategy has emerged as the standard treatment for sepsis or septic shock despite its unknown efficacy. This study aimed to assess the efficacy of prolonged versus intermittent ß-lactam antibiotics infusion on outcomes in sepsis or septic shock patients by conducting a systematic review and meta-analysis. METHODS: A thorough search was conducted on MEDLINE, the Cochrane Central Register of Controlled Trials, and the Igaku Chuo Zasshi databases. Randomized controlled trials (RCTs) comparing mortality between prolonged and intermittent infusion in adult patients with sepsis or septic shock were included. The primary outcome was hospital mortality. The secondary outcomes were the attainment of the target plasma concentration, clinical cure, adverse events, and occurrence of antibiotic-resistant bacteria. We performed a subgroup analysis stratified according to the year of publication before or after 2015 and a trial sequential analysis (TSA). The Der Simonian-Laird random-effects models were subsequently used to report the pooled risk ratios (RR) with confidence intervals (CI). RESULTS: We identified 2869 studies from the 3 databases, and 13 studies were included in the meta-analysis. Hospital mortality did not decrease (RR 0.69 [95%CI 0.47-1.02]) in the prolonged infusion group. The attainment of the target plasma concentration and clinical cure significantly improved (RR 0.40 [95%CI 0.21-0.75] and RR 0.84 [95%CI 0.73-0.97], respectively) in the prolonged infusion group. There were, however, no significant differences in the adverse events and the occurrence of antibiotic-resistant bacteria between the groups (RR 1.01 (95%CI 0.95-1.06) and RR 0.53 [95%CI 0.10-2.83], respectively). For the subgroup analysis, a significant improvement in hospital mortality or clinical cure was reported in studies published in or after 2015 (RR 0.66 [95%CI 0.44-0.98] and RR 0.67 [95%CI 0.50-0.90], respectively). The results of the TSA indicated an insufficient number of studies for a definitive analysis. CONCLUSIONS: The prolonged infusion of ß-lactam antibiotics significantly improved upon attaining the target plasma concentration and clinical cure without increasing the adverse event or the occurrence of antibiotic-resistant bacteria. Prolonged infusion could not improve hospital mortality although an improvement was shown for studies published in or after 2015. Further studies are warranted as suggested by our TSA results.

A Ruptured Mediastinal Bronchial Artery Aneurysm Treated with Urgent Thoracic Endovascular Aortic Repair.

Bronchial artery aneurysms (BAA) are a rare but potentially life-threatening complications because of the massive hemothorax or hemoptysis that occurs with ruptures. A 79-year-old woman was transferred to our hospital because of the sudden onset of back pain, syncope, and subsequent hypotension. Computed tomography showed a left BAA with bilateral hemothorax and hemomediastinum. Transcatheter bronchial artery embolization failed because of the anatomical location, and she went into cardiopulmonary arrest. Cardiopulmonary resuscitation was performed with successful revival. Urgent thoracic endovascular aortic repair to cover the root of the left bronchial artery was successful, and she survived without any neurological deficits.