Patient experience with bronchoscopy: topical versus monitored anesthesia.

BACKGROUND: This study aimed to compare patient experiences during bronchoscopy procedures using either topical anesthesia (TA) or monitored anesthesia care (MA). The goal was to identify circumstances where patients could achieve similar levels of tolerance and satisfaction using only TA, especially in resource-limited settings. METHODS: This study included consecutive patients who underwent bronchoscopy with either TA or MA. Data collected included demographics, indications for bronchoscopy, procedure time, and complications during the procedure. A quality assurance survey was administered to assess patient experience and satisfaction with both procedures. A pre-specified subgroup analysis was performed based on procedure invasiveness and time. RESULTS: This study enrolled 350 (TA 251; MA 99) patients, with an average age of 65 years. Main indications for bronchoscopy included tumor diagnosis (38%), esophageal cancer staging (18%), and pulmonary infection (17%). The average duration of the procedures was 20 min, with MA being associated with a significantly longer procedure time than TA (31 min vs. 16 min; P < 0.001). The overall satisfaction rating with bronchoscopy was significantly higher in the MA group (visual analogue scale, 8.9 vs. 8.2; P = 0.001). Subgroup analyses showed that when less invasive or shorter procedures were performed, TA patients reported tolerance and satisfaction levels comparable to MA patients. CONCLUSIONS: Bronchoscopy with MA offered patients a better experience and greater satisfaction; however, in settings with limited resources, TA alone may provide similar levels of patient tolerance and satisfaction during less invasive or shorter procedures.

Monitoring of T790M in plasma ctDNA of advanced EGFR-mutant NSCLC patients on first- or second-generation tyrosine kinase inhibitors.

BACKGROUND: The T790M mutation is the major resistance mechanism to first- and second-generation TKIs in EGFR-mutant NSCLC. This study aimed to investigate the utility of droplet digital PCR (ddPCR) for detection of T790M in plasma circulating tumor DNA (ctDNA), and explore its impact on prognosis. METHODS: This prospective study enrolled 80 advanced lung adenocarcinoma patients treated with gefitinib, erlotinib, or afatinib for TKI-sensitizing mutations between 2015 and 2019. Plasma samples were collected before TKI therapy and at tri-monthly intervals thereafter. Genotyping of ctDNA for T790M was performed using a ddPCR EGFR Mutation Assay. Patients were followed up until the date of death or to the end of 2021. RESULTS: Seventy-five of 80 patients experienced progressive disease. Fifty-three (71%) of 75 patients underwent rebiopsy, and T790M mutation was identified in 53% (28/53) of samples. Meanwhile, plasma ddPCR detected T790M mutation in 23 (43%) of 53 patients. The concordance rate of T790M between ddPCR and rebiopsy was 76%, and ddPCR identified 4 additional T790M-positive patients. Ten (45%) of 22 patients who did not receive rebiopsy tested positive for T790M by ddPCR. Serial ddPCR analysis showed the time interval from detection of plasma T790M to objective progression was 1.1 (0-4.1) months. Compared to 28 patients with rebiopsy showing T790M, the overall survival of 14 patients with T790M detected solely by ddPCR was shorter(41.3 [95% CI, 36.6-46.0] vs. 26.6 months [95% CI, 9.9-43.3], respectively). CONCLUSION: Plasma ddPCR-based genotyping is a useful technology for detection and monitoring of the key actionable genomic alteration, namely, T790M, in patients treated with gefitinib, erlotinib, or afatinib for activating mutations, to achieve better patient care and outcome.

Readmission outcomes following infectious hospitalization: same-care unit performed better than different-care unit.

BACKGROUND: Previous studies showed that same-hospital readmission is associated with better outcomes than different-hospital readmission. However, little is known about whether readmission to the same care unit (same-care unit readmission) after infectious hospitalization performs better than readmission to a different care unit at the same hospital (different-care unit readmission). METHODS: This retrospective study screened patients rehospitalized within 30 days following admission to two acute medical wards for infectious diseases from 2013 to 2015 and included only those readmitted for unplanned medical reasons. Outcomes of interest included hospital mortality and length of stay of readmitted patients. RESULTS: Three hundred and fifteen patients were included; of those, 149(47%) and 166(53%) were classified as same-care unit and different-care unit readmissions, respectively. Same-care unit patients were more likely to be older(76 years vs. 70 years; P = 0.001), have comorbid chronic kidney disease(20% vs. 9%; P = 0.008), and have a shorter time to readmission(13 days vs. 16 days; P = 0.020) than different-care unit patients. Univariate analysis showed that same-care unit patients had a shorter length of stay than different-care unit patients(13 days vs. 18 days; P = 0.001), but had similar hospital mortality(20% vs. 24%; P = 0.385). The multivariable linear regression model indicated that same-care unit readmission was associated with a 5-day shorter hospital stay than different-care unit readmission(P = 0.002). CONCLUSION: Among patients readmitted within 30 days after hospitalization for infectious diseases, same-care unit readmission was associated with a shorter length of hospital stay than different-care unit readmission. Whenever feasible, it is encouraged to allocate a readmitted patient to the same care unit in hope of pursuing continuity and quality of care.

Biological Activities of Citrus aurantium Leaf Extract by Optimized Ultrasound-Assisted Extraction.

Several studies have explored the biological activities of Citrus aurantium flowers, fruits, and seeds, but the bioactivity of C. aurantium leaves, which are treated as waste, remains unclear. Thus, this study developed a pilot-scale ultrasonic-assisted extraction process using the Box-Behnken design (BBD) for the optimized extraction of active compounds from C. aurantium leaves, and their antityrosinase, antioxidant, antiaging, and antimicrobial activities were evaluated. Under optimal conditions in a 150× scaleup configuration (a 30 L ultrasonic machine) of a pilot plant, the total phenolic content was 69.09 mg gallic acid equivalent/g dry weight, which was slightly lower (3.17%) than the theoretical value. The half maximal inhibitory concentration of C. aurantium leaf extract (CALE) for 2,2-diphenyl-1-picrylhydrazyl-scavenging, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)-scavenging, antityrosinase, anticollagenase, antielastase and anti-matrix metalloprotein-1 activities were 123.5, 58.5, 181.3, 196.4, 216.3, and 326.4 mg/L, respectively. Moreover, the minimal inhibitory concentrations for bacteria and fungi were 150-350 and 500 mg/L, respectively. In total, 17 active compounds were detected in CALE-with linalool, linalyl acetate, limonene, and α-terpineol having the highest concentrations. Finally, the overall transdermal absorption and permeation efficiency of CALE was 95.9%. In conclusion, our CALE demonstrated potential whitening, antioxidant, antiaging, and antimicrobial activities; it was also nontoxic and easily absorbed into the skin as well as inexpensive to produce. Therefore, it has potential applications in various industries.

Application of a pre-emptive question and answer platform to improve the level of satisfaction during family meetings in general medical wards.

BACKGROUND: A successful family meeting is key to family-centered care and may foster communication and improve the level of satisfaction of the family in terms of communication. In this study, we evaluated whether a proactive communication channel could improve the level of satisfaction of family members following a family meeting in a general medical ward setting. METHODS: We conducted a pre- and post-study to compare the level of satisfaction of a family with a family meeting before (N = 39) and after (N = 29) intervention in two general medical wards of a tertiary-care referral center. The intervention included a pre-emptive question and answer platform and a written response to family-raised queries in addition to a regular setting. Following each family meeting, family members were requested to fill a 10-item survey assessing their levels of satisfaction. RESULTS: The characteristics of the family members in terms of demographics, education levels, and previous experiences with family meetings in the pre- and post-intervention groups were similar. The scores in all the items that indicated the level of satisfaction significantly improved after intervention. The overall score for satisfaction increased from 85 (interquartile range, 80-95) to 98 (interquartile range, 93-100; P < 0.001). CONCLUSIONS: Compared with conventional practice, the inclusion of a proactive communication platform along with a written response to raised queries as a part of family meetings improved the satisfaction levels of the family in terms of the content and process of the meeting in the general ward setting. Further studies are needed to delineate the optimal timing and use of such a communication modality.

Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described. METHODS: In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal-Wallis rank tests and Chi-squared tests were used to compare between-etiology differences. RESULTS: From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia. CONCLUSION: This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

A 3D Plasmonic Crossed-Wire Nanostructure for Surface-Enhanced Raman Scattering and Plasmon-Enhanced Fluorescence Detection.

In this manuscript, silver nanowire 3D random crossed-wire woodpile (3D-RCW) nanostructures were designed and prepared. The 3D-RCW provides rich "antenna" and "hot spot" effects that are responsive for surface-enhanced Raman scattering (SERS) effects and plasmon-enhanced fluorescence (PEF). The optimal construction mode for the 3D-RCW, based on the ratio of silver nanowire and control compound R6G, was explored and established for use in PEF and SERS analyses. We found that the RCW nanochip capable of emission and Raman-enhanced detections uses micro levels of analysis volumes. Consequently, and SERS and PEF of pesticides (thiram, carbaryl, paraquat, fipronil) were successfully measured and characterized, and their detection limits were within 5 µM~0.05 µM in 20 µL. We found that the designed 3D plasmon-enhanced platform cannot only collect the SERS of pesticides, but also enhance the fluorescence of a weak emitter (pesticides) by more than 1000-fold via excitation of the surface plasmon resonance, which can be used to extend the range of a fluorescence biosensor. More importantly, solid-state measurement using a 3D-RCW nanoplatform shows promising potential based on its dual applications in creating large SERS and PEF enhancements.

Gastrointestinal complications are associated with a poor outcome in non-critically ill pneumonia patients.

BACKGROUND: Development of gastrointestinal (GI) complications is adversely associated with prognosis in the critically ill. However, little is known about their impact on the outcome of non-critically ill patients. In this study, we aimed to investigate the incidence of GI complications and their influence on prognosis of hospitalized pneumonia patients. METHODS: Adult patients admitted with a diagnosis of pneumonia from 2012 to 2014 were included. Medical records were reviewed to obtain patients' demographics, physical signs, comorbidities, laboratory results, clinical events, and the Confusion, Urea, Respiratory rate, Blood pressure and age ≥ 65 (CURB-65) score was calculated to assess the severity of pneumonia. GI complications, including bowel distension, diarrhea, GI bleeding and ileus, were evaluated during the first 3 days of hospitalization and their association with patient outcomes, such as hospital mortality and length of stay, was analyzed. RESULTS: A total of 1001 patients were enrolled, with a mean age of 73.7 years and 598 (59%) male. Among them, 114 (11%) patients experienced at least one GI complication and diarrhea (5.2%) was the most common. The hospital mortality was 14% and was independently associated with an increase in the CURB-65 score (odds ratio [OR] 1.952 per point increase; 95% confidence interval [CI] 1.516-2.514), comorbid malignancy (OR 1.943; 95% CI 1.209-3.123), development of septic shock (OR 25.896; 95% CI 8.970-74.765), and the presence of any GI complication (OR 1.753; 95% CI 1.003-3.065). CONCLUSIONS: Compared to a critical care setting, GI complications are not commonly observed in a non-critical care setting; however, they still have a negative impact on prognosis of pneumonia patients, including higher mortality and prolonged length of hospital stay.

Differential roles of comorbidity burden and functional status in elderly and non-elderly patients with infections in general wards.

BACKGROUND: Differential roles of comorbidity burden, functional status and severity of illness in elderly and non-elderly patients admitted to general wards with infections in terms of short-term and long-term mortality remain poorly understood and worth further investigation. METHODS: From 2011 to 2013, patients admitted to general wards with a main diagnosis of infections were included and their Barthel index, Charlson comorbidity index and Pitt bacteremia score were collected to evaluate their association with in-hospital and 1-year outcomes of the study cohort. Age stratification was applied for all outcome analysis. RESULTS: A total of 2481 patients were identified, with main diagnoses of pneumonia (57%), urinary tract infection (28%) and intra-abdominal infection (18%). In-hospital mortality occurred in 291 (12%) of the population and was independently predicted by Barthel index ≤50 (odds ratio [OR] 5.67 and 2.73, respectively) and Charlson comorbidity index >2 (OR 1.49 and 2.87, respectively) in both elderly and non-elderly patients. Among 2190 hospital survivors, Barthel index ≤50 (hazard ratio [HR] 1.38) and Charlson comorbidity index >2 (HR 1.96) were associated with a higher hazard of 1-year mortality in elderly patients. However, only Charlson comorbidity index >2 (HR 2.87) was a significant characteristic of non-elderly patients to be correlated with higher 1-year mortality. CONCLUSION: This study found that functional status on admission was predictive of in-hospital mortality of general patients with infections irrespective of age groups; however, it played a differential role in 1-year mortality in between elderly and non-elderly patients, emphasizing the importance of functional assessment among the elderly.

Metformin use mitigates the adverse prognostic effect of diabetes mellitus in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Among patients with chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM) is a common comorbidity and is probably associated with increased systemic inflammation and worse prognosis. Metformin, with its pleiotropic anti-inflammatory and antioxidant actions, may offer theoretical benefits in COPD patients with DM. Thus, this study aimed to investigate the effects of DM and metformin use on mortality in the clinical trajectory of COPD. METHODS: This was a retrospective cohort study comprising patients with spirometry-confirmed COPD and an age of ≥40 years from 2008 to 2014. The primary outcome of interest was all-cause mortality. We evaluated the effects of DM on mortality through the clinical course of COPD and we also assessed the impact of metformin use on survival of the COPD population. RESULTS: Among 4231 COPD patients, 556 (13%) had DM, and these patients had 1.62 times higher hazards of 2-year mortality than those without DM (95% confidence interval [CI], 1.15-2.28) after adjusting for age, gender, COPD stage, comorbidities and prior COPD hospitalization. Over a 2-year period, metformin users had a significantly lower risk of death (hazard ratio, 0.46; 95% CI, 0.23-0.92) compared with non-metformin users in patients with coexistent COPD and DM. Moreover, metformin users had similar survival to COPD patients without DM. CONCLUSIONS: This study shows that DM is associated with an increased risk of death in COPD patients and metformin use seems to mitigate the hazard. Our findings suggest a potential role of metformin in the management of DM in COPD.

Atypical cells in pathology of endobronchial ultrasound-guided transbronchial biopsy of peripheral pulmonary lesions: incidence and clinical significance.

BACKGROUND: Atypical cells may occasionally be the only pathologic finding in radial-probe endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) of peripheral pulmonary lesions (PPLs); however, it is uncertain how often we encounter such a situation and what clinical features can be used to identify these ambiguous PPLs, which are more likely to be malignant. METHODS: From 2009 to 2016, consecutive patients referred for EBUS-guided TBB of PPLs and with pathology reports indicating atypical cells alone were included. Medical records were reviewed to extract patient demographics, clinical characteristics, procedural details and complications. The primary outcome was the final diagnosis of the PPLs on subsequent investigation. Multivariate logistic regression analysis was used to identify independent factors associated with a final malignant diagnosis. RESULTS: One hundred sixty-five (7.2%) of 2291 patients had non-diagnostic TBB showing atypical cells. Benign and malignant diagnoses were subsequently obtained in 45 (27%) and 120 (73%) patients, respectively. The leading malignancy was lung adenocarcinoma; of note, a variety of benign lesions revealed cellular atypia on pathology, in particular, chronic inflammation, tuberculosis and pneumonia. Multivariate analysis indicated lesion appearance [solid vs. others; odds ratio (OR) 7.93; 95% confidence interval (CI) 2.94-21.40; P < 0.001] and probe position (adjacent to vs. within; OR 3.36; 95% CI 1.11-10.15; P = 0.032) were two significant factors predictive of a final diagnosis of malignancy. CONCLUSIONS: One out of 14 EBUS-guided TBB procedures for PPLs exhibited atypical cells on pathology. Meticulous management strategies should be formulated to deal with these instances after taking into consideration lesion appearance, probe position and patient preferences.

Radial endobronchial ultrasound-guided transbronchial biopsy for peripheral pulmonary malignancy: biopsy- or brushing-first?

BACKGROUND: Radial endobronchial ultrasound (R-EBUS)-guided transbronchial biopsy (TBB) is a common diagnostic modality for peripheral pulmonary lesions; however, there is uncertainty about the optimal sequence of TBB and bronchial brushing during the procedure. Thus, we aimed to investigate whether a biopsy-first or brushing-first strategy confers a better diagnostic yield and safety signal for R-EBUS-guided procedures for peripheral pulmonary malignancy. METHODS: From January 2017 to June 2018, consecutive patients referred for R-EBUS-guided TBB and bronchial brushing of peripheral pulmonary lesions and with a final malignant diagnosis were included. Patients were placed in a biopsy-first (biopsy followed by brushing) or a brushing-first (brushing followed by biopsy) group. The outcomes of interest were the diagnostic yield and complication profile of the procedures. Multivariate logistic regression and subgroup analysis were used to assess the impact of the procedure strategy. RESULTS: A total of 438 patients were included and the diagnostic yield of R-EBUS-guided TBB plus brushing for peripheral pulmonary malignancy was 73%. The diagnostic yield was associated with the solid lesion appearance (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.08-3.75) and R-EBUS probe position within the lesion (OR 1.92; 95% CI 1.08-3.42), and the yield rates were comparable between the biopsy-first and brushing-first strategies. Moreover, the safety signal did not differ between the two groups. CONCLUSIONS: The two procedure strategies were indistinguishable in terms of diagnostic efficacy and adverse events for patients with peripheral pulmonary malignancy. Current evidence indicates that in patients with peripheral pulmonary lesions suspected of being malignant, either biopsy-first or brushing-first is a viable and acceptable diagnostic strategy during R-EBUS-guided procedures.

Erythropoietin reduces nerve demyelination, neuropathic pain behavior and microglial MAPKs activation through erythropoietin receptors on Schwann cells in a rat model of peripheral neuropathy.

Neuroprotective effects of erythropoietin (EPO) on peripheral nerve injury remain uncertain. This study investigated the efficacy of EPO in attenuating median nerve chronic constriction injury (CCI)-induced neuropathy. Animals received an intraneural injection of EPO at doses of 1,000, 3,000, or 5,000 units/kg 15 min before median nerve CCI. Afterwards, the behavioral and electrophysiological tests were conducted. Immunohistochemistry and immunoblotting were used for qualitative and quantitative analysis of microglial and mitogen-activated protein kinases (MAPKs), including p38, JNK, and ERK, activation. Enzyme-linked immunosorbent assay and microdialysis were applied to measure pro-inflammatory cytokine and glutamate responses, respectively. EPO pre-treatment dose-dependently ameliorated neuropathic pain behavior, decreased microglial and MAPKs activation, and diminished the release of pro-inflammatory cytokines and glutamate in the ipsilateral cuneate nucleus after CCI. Moreover, EPO pre-treatment preserved myelination of the injured median nerve on morphological investigation and suppressed injury-induced discharges. We also observed that EPO receptor (EPOR) expression was up-regulated in the injured nerve after CCI. Double immunofluorescence showed that EPOR was localized to Schwann cells. Furthermore, siRNA-mediated knockdown of EPOR expression eliminated the therapeutic effects of EPO on attenuating the microglial and MAPKs activation, pro-inflammatory cytokine responses, injury discharges, and neuropathic pain behavior in CCI rats. In conclusion, binding of EPO to its receptors on Schwann cells maintains myelin integrity and blocks ectopic discharges in the injured median nerve, that in the end contribute to attenuation of neuropathic pain via reducing glutamate release from primary afferents and inhibiting activation of microglial MAPKs and production of pro-inflammatory cytokines.

A dual photoluminescence enhancement system: stabilization of a water soluble AIEE fluorogen using silver nanowire.

This manuscript describes the preparation of water soluble aggregation-induced emission enhancement (AIEE)-based fluorescent organic nanoparticles (FONs). The fluorescence diversity of the FONs was investigated in the presence of silver nanowires. We observed that the emission of the FONs can be enhanced by mixing with the nanowires, which is believed to originate from resonance between the emission of the FONs and the surface plasmon resonances of the metal surface. That is, the AIEE phenomenon was promoted according to the metal-enhanced fluorescence (MEF) mechanism that can be used to build up a novel double emission enhancement (DEE) platform and to extend the range of AIEE applications. The systemic fluorescence enhancement, lifetime and photostability were measured and the AIEE-MEF evaluation and the interaction between the FONs and nanowires were discussed based on the obtained spectral data and SEM and fluorescent microscopy images.

The value of repeat radial-probe endobronchial ultrasound-guided transbronchial biopsy after initial non-diagnostic results in patients with peripheral pulmonary lesions.

BACKGROUND: Radial-probe endobronchial ultrasound (rEBUS)-guided transbronchial biopsy (TBB) is invaluable in the diagnosis of peripheral pulmonary lesions (PPLs); however, in certain instances, the procedure has to be repeated because of initial non-diagnostic procedure(s). Little if any literature has been published on this issue. Therefore, the aim of this study was to investigate the utility of repeat rEBUS-guided TBB in achieving a definitive diagnosis of PPLs. METHODS: All patients who underwent rEBUS-guided TBB of PPLs at National Taiwan University Hospital between 2011 and 2015 and had a repeat procedure after non-diagnostic initial procedures were identified as the study subjects. The primary outcome of interest was the diagnostic yield of repeat rEBUS-guided TBB for PPLs. Also, we sought to discover features associated with the yield of repeat procedures. RESULTS: Forty-three (11%) out of 384 patients with initial non-diagnostic TBB were included for analysis. A diagnosis of PPLs was able to be confirmed with repeat TBB in 23(53%) patients. The pathology of the first TBB was significantly associated with the yield of repeat procedures (P = 0.011). Further, patients with normal lung tissue in initial pathology rarely (2/12, 17%) had a definite diagnosis on repeat TBB. Yet, patients with pathology showing atypical cells and other non-specific findings were more likely (21/31, 68%) to obtain a confirmed diagnosis. The diagnostic yield of repeat procedures was not affected by the size, location or CT appearance of the lesions, or position of the rEBUS probe. No death or other serious adverse events occurred with the repeat rEBUS-guided procedures. CONCLUSIONS: If clinically indicated, it is reasonable to repeat rEBUS-guided TBB after an initial non-diagnostic procedure as the diagnostic yield will be at least 50% and the side effect profile is favorable.

Preadmission tracheostomy is associated with better outcomes in patients with prolonged mechanical ventilation in the postintensive care respiratory care setting.

BACKGROUND/PURPOSE: Prolonged mechanical ventilation (PMV) is the most common situation where tracheostomy is indicated for intensive care unit (ICU) patients. However, it is unknown if this procedure confers survival benefits on PMV patients in a post-ICU setting. METHODS: Patients who were admitted to the specialized weaning unit from 2005 to 2008 and received PMV were included in this study. On admission, data pertaining to patient characteristics, physiologic status, and type of artificial airway (tracheostomy vs. no tracheostomy) were obtained. Outcomes of tracheostomized and nontracheostomized patients were evaluated using multivariate Cox proportional hazards and propensity score-matching models. The primary outcome of interest was 1-year survival. RESULTS: A total of 401 patients (mean age 74.4 years, 204 male) were identified. In multivariate analyses, higher Acute Physiology and Chronic Health Evaluation II score [hazard ratio (HR) = 1.061, 95% confidence interval (CI) = 1.016-1.107] and presence of comorbidities, including congestive heart failure (HR = 1.562, 95% CI = 1.119-2.181), malignancy (HR = 1.942, 95% CI = 1.306-2.885), and liver cirrhosis (HR = 2.373, 95% CI = 1.015-5.544), were independently associated with 1-year mortality. An association between having tracheostomy and a better 1-year outcome was observed (HR = 0.625, 95% CI = 0.453-0.863). The matched cohort study also demonstrated a favorable 1-year survival for tracheostomized patients, and these patients had significantly lower in-hospital mortality (24% vs. 36%, p = 0.049) and risk of ventilator-associated pneumonia (10% vs. 20%, p = 0.030) than nontracheostomized ones. CONCLUSION: Preadmission tracheostomy may be associated with better outcomes of PMV patients in a post-ICU respiratory care setting. The findings suggest that this procedure should be recommended before PMV patients are transferred to specialized weaning units.

Neurosteroid Allopregnanolone Suppresses Median Nerve Injury-induced Mechanical Hypersensitivity and Glial Extracellular Signal-regulated Kinase Activation through γ-Aminobutyric Acid Type A Receptor Modulation in the Rat Cuneate Nucleus.

BACKGROUND: Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats. METHODS: We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI. We subsequently employed microinjection of a mitogen-activated protein kinase kinase (ERK kinase) inhibitor, PD98059, to clarify the role of ERK phosphorylation in neuropathic pain development. Furthermore, we explored the effects of allopregnanolone (by mouth), intra-CN microinjection of γ-aminobutyric acid type A receptor antagonist (bicuculline) or γ-aminobutyric acid type B receptor antagonist (phaclofen) plus allopregnanolone, and allopregnanolone synthesis inhibitor (medroxyprogesterone; subcutaneous) on ERK activation and CCI-induced behavioral hypersensitivity. RESULTS: At 7 days post-CCI, p-ERK levels in ipsilateral CN were significantly increased and reached a peak. PD98059 microinjection into the CN 1 day after CCI dose-dependently attenuated injury-induced behavioral hypersensitivity (withdrawal threshold [mean ± SD], 7.4 ± 1.1, 8.7 ± 1.0, and 10.3 ± 0.8 g for 2.0, 2.5, and 3.0 mM PD98059, respectively, at 7 days post-CCI; n = 6 for each dose). Double immunofluorescence showed that p-ERK was localized to both astrocytes and microglia. Allopregnanolone significantly diminished CN p-ERK levels, glial activation, proinflammatory cytokines, and behavioral hypersensitivity after CCI. Bicuculline, but not phaclofen, blocked all effects of allopregnanolone. Medroxyprogesterone treatment reduced endogenous CN allopregnanolone and exacerbated nerve injury-induced neuropathic pain. CONCLUSIONS: Median nerve injury-induced CN glial ERK activation modulated the development of behavioral hypersensitivity. Allopregnanolone attenuated glial ERK activation and neuropathic pain via γ-aminobutyric acid type A receptors. Reduced endogenous CN allopregnanolone after medroxyprogesterone administration rendered rats more susceptible to CCI-induced neuropathy.