Although the negative impact of immunosuppression on survival in patients with acute respiratory distress syndrome (ARDS) treated by extracorporeal membrane oxygenation (ECMO) is well known, ...short-term outcomes such as successful weaning rate from ECMO and subgroups benefit most from ECMO remain to be determined. The aims of this study were (1) to identify the association between immunocompromised status and weaning from ECMO in patients of ARDS, and (2) to identify subgroups of immunocompromised patients who may benefit from ECMO.
This retrospective cohort study enrolled patients who received ECMO for ARDS from 2010 to 2020. Immunocompromised status was defined as having a hematological malignancy, active solid tumor, solid organ transplant, or autoimmune disease.
This study enrolled 256 ARDS patients who received ECMO, of whom 68 were immunocompromised. The multivariable analysis showed that immunocompromised status was not independently associated with failure to wean from ECMO. In addition, the patients with an autoimmune disease (14/24, 58.3%) and organ transplantation (3/3, 100%) had a numerically higher weaning rate from ECMO than other immunocompromised patients. For causes of ARDS, most patients with pulmonary hemorrhage (6/8, 75%) and aspiration (5/9, 55.6%) could be weaned from ECMO, compared to only a few of the patients with interstitial lung disease (2/9, 22.2%) and sepsis (1/4, 25%).
Immunocompromised status was not an independent risk factor of failure to wean from ECMO in patients with ARDS. For patients with pulmonary hemorrhage and aspiration-related ARDS, ECMO may be beneficial as bridge therapy.
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Breast cancer stands as the most prevalent and heterogeneous malignancy affecting women globally, posing a substantial health concern. Enhanced comprehension of tumor pathology and ...the development of novel therapeutics are pivotal for advancing breast cancer treatment. Contemporary breast cancer investigation heavily leans on in vivo models and conventional cell culture techniques. Nonetheless, these approaches often encounter high failure rates in clinical trials due to species disparities and tissue structure variations. To address this, three-dimensional cultivation of organoids, resembling organ-like structures, has emerged as a promising alternative. Organoids represent innovative in vitro models that mirror in vivo tissue microenvironments. They retain the original tumor's diversity and facilitate the expansion of tumor samples from diverse origins, facilitating the representation of varying tumor stages. Optimized breast cancer organoid models, under precise culture conditions, offer benefits including convenient sample acquisition, abbreviated cultivation durations, and genetic stability. These attributes ensure a faithful replication of in vivo traits of breast cancer cells. As intricate cellular entities boasting spatial arrangements, breast cancer organoid models harbor substantial potential in precision medicine, organ transplantation, modeling intricate diseases, gene therapy, and drug innovation. This review delivers an overview of organoid culture techniques and outlines future prospects for organoid modeling.
Abstract Rationale The effectiveness of varenicline for smoking cessation has been established, but little is known about the psychological processes that mediate this clinical outcome. Objectives ...This study evaluated the effect of a single dose of varenicline on tonic and cue-provoked changes in craving, withdrawal, and affect using a randomized, double-blind, placebo-controlled, cross-over design. Methods Following overnight abstinence, 38 non-treatment-motivated smokers received either varenicline 2 mg or matched placebo, then tonic measures of craving, withdrawal, and positive and negative affect were obtained at 30-min intervals. At 4-h post-administration, a cue exposure session obtained the same subjective measures at three time-points following the physical handling of a lit cigarette versus the sharpening and handling of a pencil. Results At 4-h post-administration, varenicline reduced tonic craving as well as craving across the smoking and neutral cue conditions, relative to placebo. By contrast, the capacity of the smoking cue to enhance craving relative to the neutral cue was unaffected by varenicline. Measures of withdrawal and positive and negative affect produced mixed results. Conclusions Acute varenicline selectively attenuates tonic but not cue-provoked craving. This dissociation provides insight into the specific psychological processes that might mediate the effectiveness of varenicline, and highlights cue-provoked craving as a discrete target for advancing smoking cessation pharmacotherapy.
Study Type – Therapy (cohort)
Level of Evidence 2b
What’s known on the subject? and What does the study add?
We know that bladder‐relaxing agents antimuscrinics act on symptoms of overactive bladder ...and are the first treatment in such patients. We know that fesoterodine is a newer antimuscarinic with a good activity safety profile.
This study adds to the experience that changing the dose of antimuscrinics as fesoterodine is often needed by patients, that the decision can be made by the patients, and the change in dose adds to the clinical result.
OBJECTIve
To assess changes in overactive bladder (OAB) symptoms and patient‐reported outcomes in a post hoc analysis in which subjects from a 12‐week, open‐label, flexible‐dose fesoterodine study were stratified according to whether they opted for dose escalation.
PATIENTS AND METHODS
Subjects with OAB (eight or more micturitions and three or more urgency episodes per 24 h) who reported dissatisfaction with tolterodine within 2 years of screening received fesoterodine 4 mg once daily for 4 weeks, with an optional dose increase to 8 mg after week 4 based on discussion of efficacy and tolerability between the subject and investigator. Subjects completed 5‐day diaries, the Patient Perception of Bladder Condition (PPBC) and Urgency Perception Scale (UPS) at baseline and weeks 4 and 12, and the Overactive Bladder Questionnaire (OAB‐q) at baseline and week 12. Subjects rated treatment satisfaction at week 12.
RESULTS
Dose escalation to 8 mg at week 4 was chosen by 255 (50%) of 513 subjects. At baseline, subjects who opted for dose escalation at week 4 (escalators) had significantly higher means for all diary variables except urgency urinary incontinence (UUI) episodes, significantly greater OAB‐q Symptom Bother scores and significantly lower OAB‐q health‐related quality of life (HRQL) scores (all P < 0.05) compared to subjects who did not opt for dose escalation (non‐escalators). There was no significant difference in the percentage of escalators (51%) and non‐escalators (48%) who reported at least one UUI episode on baseline diary. At week 4 (before the decision to escalate was made), all outcomes were significantly improved vs baseline among both groups (all P < 0.0001), although non‐escalators had significantly greater improvements in all diary variables and in PPBC and UPS scores than escalators (all P < 0.05), and the 5‐day diary‐dry rate (i.e. the percentage of subjects with at least one UUI episode on baseline diary and no UUI episodes on week 4 diary) was significantly higher (P= 0.0016) among non‐escalators (62%) than among escalators (42%). At week 12, all outcomes were again significantly improved vs baseline among both groups (all P < 0.0001). There were no significant differences between non‐escalators and escalators in week 12 improvements for most diary variables, UPS scores, OAB‐q Symptom Bother scores, the diary‐dry rate (68% vs 60%) or the percentage of subjects who reported treatment satisfaction (82% vs 78%). However, escalators still had significantly greater improvements from baseline in urgency episodes, PPBC scores and OAB‐q total HRQL and Coping domains (P < 0.05). Adverse event rates were similar between non‐escalators and escalators. Dry mouth was the most frequently reported adverse event; most cases were mild.
CONCLUSION
Flexible‐dose fesoterodine significantly improved OAB symptoms and patient‐reported outcomes in subjects who chose to remain on the initial 4‐mg dose, as well as in the 50% of subjects who escalated to the 8‐mg dose after 4 weeks. Non‐escalators had significantly fewer OAB symptoms at baseline and significantly greater improvements than escalators before dose escalation. Escalators showed increased symptom relief after dose escalation; improvements in most outcomes were similar among non‐escalators and escalators by week 12. Flexible‐dose fesoterodine was well tolerated, with similar adverse‐event profiles observed in the escalator and non‐escalator groups. These results may help clinicians to identify patients more likely to require fesoterodine 8 mg to achieve maximum relief of OAB symptoms and thus facilitate dose escalation in these patients.
In the accepted paper, the authors’ affiliation has been wrongly typeset as People’s Republic of China, but this should read Taiwan. The correct affiliations are shown below.
Extracorporeal membrane oxygenation (ECMO) has been repeatedly used to rescue patients with cardiopulmonary arrest. However, its clinical utility in endocrine emergencies remains unclear. Herein, we ...describe a case series of 12 patients presenting with refractory shock secondary to endocrine emergencies who were rescued by ECMO support. Patients were identified between 2005 and 2012 from our ECMO registry. The diagnostic distribution was as follows: pheochromocytoma crisis (n = 4), thyroid storm (n = 5), and diabetic ketoacidosis (n = 3). The initial presentation of pheochromocytoma crisis was indistinguishable from acute myocardial infarction (AMI) and frequently accompanied by paroxysmal hypertension and limb ischemia. Thyroid storm was characterized by hyperbilirubinemia and severe gastrointestinal bleeding, whereas neurological symptoms were common in diabetic ketoacidosis. The clinical outcomes of patients with endocrine emergencies were compared with those of 80 cases with AMI who received ECMO because of cardiogenic shock. The cardiac function and the general conditions showed a significantly faster recovery in patients with endocrine emergencies than in those with AMI. We conclude that ECMO support can be clinically useful in endocrine emergencies. The screening of endocrine diseases should be considered during the resuscitation of patients with refractory circulatory shock.
Extracorporeal cardiopulmonary resuscitation (ECPR) has gradually come to be regarded as an effective therapy, but the hospital mortality rate after ECPR is still high and unpredictable. The present ...study tested whether age-adjusted Charlson comorbidity index (ACCI) can be used as an objective selection criterion to ensure the most efficient utilization of medical resources. Adult patients (age ≥ 18 years) receiving ECPR at our institution between 2006 and 2015 were included. Data regarding ECPR events and ACCI characteristics were collected immediately after the extracorporeal membrane oxygenation (ECMO) setup. Adverse events during hospitalization were also prospectively collected. The primary endpoint was survival to hospital discharge. The second endpoint was the short-term (2-year) follow-up outcome. A total of 461 patients included in the study were grouped into low ACCI (ACCI 0⁻3) (240, 52.1%) and high ACCI (ACCI 4⁻13) (221, 47.9%) groups. The median ACCI was 2 (interquartile range (IQR): 1⁻3) and 5 (IQR: 4⁻7) for the low and high ACCI groups, respectively. Cardiopulmonary resuscitation (CPR)-to-ECMO duration was comparable between the groups (42.1 ± 25.6 and 41.3 ± 20.7 min in the low and high ACCI groups, respectively;
= 0.754). Regarding the hospital survival rate, 256 patients (55.5%) died on ECMO support. A total of 205 patients (44.5%) were successfully weaned off ECMO, but only 138 patients (29.9%) survived to hospital discharge (32.1% and 27.6% in low and high ACCI group,
= 0.291). Multivariate logistic regression analysis revealed CPR duration before ECMO run (CPR-to-ECMO duration) and a CPR cause of septic shock to be significant risk factors for hospital survival after ECPR (
= 0.043 and 0.014, respectively), whereas age and ACCI were not (
= 0.334 and 0.164, respectively). The 2-year survival rate after hospital discharge for the 138 hospital survivors was 96% and 74% in the low and high ACCI groups, respectively (
= 0.002). High ACCI before ECPR does not predict a poor outcome of hospital survival. Therefore, ECPR should not be rejected solely due to high ACCI. However, high ACCI in hospital survivors is associated with a higher 2-year mortality rate than low ACCI, and patients with high ACCI should be closely followed up.
Study Type – Therapy (cohort) Level of Evidence 2b
What’s known on the subject? and What does the study add?
Fesoterodine is an effective treatment for overactive bladder. However, the length of time ...until the effects begin to be seen was not known.
The study demonstrates that the effect of Fesoterodine 4 mg on overactive bladder symptoms can be seen at one week.
OBJECTIVE
To assess the onset of efficacy of fesoterodine 4 mg once daily on overactive bladder (OAB) symptoms after 1 week of treatment.
PATIENTS AND METHODS
This was a prespecified analysis of data collected during the first week of a 12‐week, open‐label, single‐arm, flexible‐dose study of fesoterodine. Eligible subjects were adult men and women (aged ≥ 18 years) who reported urinary frequency (eight or more micturitions per 24 h) and urgency (three or more episodes per 24 h) in 5‐day bladder diaries at baseline, and dissatisfaction with previous tolterodine or tolterodine extended‐release treatment received within 2 years of screening. All subjects received fesoterodine 4 mg once daily during the first 4 weeks of treatment (with an optional dose increase to fesoterodine 8 mg after week 4). Early onset of efficacy of fesoterodine 4 mg was assessed based on changes from baseline to week 1 in variables recorded in 5‐day bladder diaries, including total micturitions, urgency episodes, urgency urinary incontinence (UUI) episodes and nocturnal micturitions. Urgency and severe urgency episodes were defined as those rated ≥ 3 and ≥4, respectively, on the five‐point Urinary Sensation Scale (USS) (1 = no urgency, 5 = UUI); frequency‐urgency sum (a combined measure of micturition frequency and urgency) was defined as the sum of all USS ratings.
RESULTS
All bladder diary variables, including total and nocturnal micturitions, UUI episodes, urgency episodes, severe urgency episodes and frequency‐urgency sum per 24 h, were significantly improved (all P < 0.0001) after 1 week of treatment with fesoterodine 4 mg compared to baseline. The diary‐dry rate at week 1 (i.e. subjects with at least one UUI episode at baseline who subsequently reported no UUI episodes on week 1 diary) was 38%.
CONCLUSION
In this open‐label study of subjects with OAB who had been previously treated and dissatisfied with tolterodine, fesoterodine 4 mg showed a rapid onset of efficacy at 1 week.
Background/purpose Polyomavirus BK (BKV) reactivation causes allograft dysfunction in some kidney transplant recipients. The use of mammalian target of rapamycin (mTOR) inhibitor-based immunotherapy ...is associated with a lower incidence of polyomavirus-associated nephropathy compared with other immunosuppressants. This retrospective study assessed whether conversion to mTOR inhibitor-based immunotherapy directly reduced urinary BKV load. Methods A total of 63 kidney recipients were divided into mTOR inhibitor-conversion (21 patients) and nonconversion (42 patients) groups. Urinary BKV loads were determined before and at least 6 months after the conversion. Results The results demonstrated that urinary BKV titer was significantly reduced in the conversion group (3.94 ± 0.43 copies (log)/mL to 2.49 ± 0.19 copies (log)/mL) and remained unaltered in the nonconversion group (3.19 ± 0.20 copies (log)/mL to 2.90 ± 0.20 copies (log)/mL). In addition, the percentage of patients with reduced urinary BKV load was significantly higher in the conversion group (76.2% vs. 42.9%). The estimated glomerular filtration rate after 24 months mTOR inhibitor conversion was significantly increased compared with that in the nonconversion group. Conversion to mTOR-inhibitor-based immunotherapy was the only factor associated with an increase in estimated glomerular filtration rate. Conclusion This study reveals an association of conversion to mTOR-inhibitor-based immunotherapy with the reduction of urinary BKV load.
This study assessed the prevalence of the inappropriate use of over-the-counter (OTC) cold medicine among adolescents and examined the relationships between knowledge, literacy, and the inappropriate ...use of OTC cold medicine. In 2015, a national representative sample of 6812 students from primary, middle, and high schools completed a survey in Taiwan. Self-administered questionnaires were collected. The results indicated that 22% of adolescents had taken OTC cold medicine in the past year, and 28.5% of them had taken inappropriate dosages. In addition, 15% of adolescents bought OTC cold medicine in the past year, 27% of them did not consult pharmacists. More than half of the adolescents surveyed had misperceptions about cold medicine. Multivariate analysis results indicated that adolescents who had lower levels of cold medicine knowledge, lower medication label literacy, and lower self-efficacy were more likely to engage in the inappropriate use of OTC cold medicine.
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