Success rates of intensive aphasia therapy: real-world data from 448 patients between 2003 and 2020.

BACKGROUND: Aphasia is a devastating consequence after stroke, affecting millions of patients each year. Studies have shown that intensive speech and language therapy (SLT) is effective in the chronic phase of aphasia. Leveraging a large single-center cohort of persons with aphasia (PWA) including patients also in the subacute phase, we assessed treatment effects of intensive aphasia therapy in a real-world setting. METHODS: Data were collected at the Aachen aphasia ward in Germany between 2003 and 2020. Immediate treatment responses across different language domains were assessed with the Aachen Aphasia Test (AAT) using single-case psychometrics, conducted before and after 6-7 weeks of intensive SLT (10 h per week, median (IQR) dosage = 68 (61-76)). We adjusted for spontaneous recovery in subacute patients. Differential treatment effects between subgroups of chronicity and predictors of therapy response were investigated. RESULTS: A total of 448 PWA were included (29% female, median (IQR) age = 54 (46-62) years, median (IQR) time post-onset = 11 (6-20) months) with 12% in the early subacute, 15% in the late subacute and 74% in the chronic phase of aphasia. The immediate responder rate was 59%. Significant improvements in all AAT subtests und subscales were observed hinting at broad effectiveness across language domains. The degree of therapy-induced improvement did not differ between the chronicity groups. Time post-onset, dosage of therapy and aphasia severity at the beginning of treatment were predictors of immediate treatment response. DISCUSSION: Intensive therapy protocols for aphasia after stroke are yielding substantial responder rates in a routine clinical setting including a wide range of patients.

Response to food restriction, but not social information use, varies seasonally in captive cardueline finches.

For songbirds, temperate winters can impose severe conditions on songbirds that threaten survival, including shorter days and often lower temperature and food availability. One well-studied mechanism by which songbirds cope with such conditions is seasonal acclimatization of thermal metabolic traits, with strong evidence for both preparative and responsive changes in thermogenic capacity (i.e., the ability to generate heat) to low winter temperature. However, a bird's ability to cope with seasonal extremes or unpredictable events is likely dependent on a combination of behavioral and physiological traits that function to maintain allostatic balance. The ability to cope with reduced food availability may be an important component of organismal response to temperate winters in songbirds. Here we compare responses to experimentally reduced food availability at different times of year in captive red crossbills (Loxia curvirostra) and pine siskins (Spinus pinus) - two species that cope with variable food resources and live in cold places - to investigate seasonal changes in the organismal response to food availability. Further, red crossbills are known to use social information to improve response to reduced food availability, so we also examine whether use of social information in this context varies seasonally in this species. We find that pine siskins and red crossbills lose less body mass during time-restricted feedings in late winter compared to summer, and that red crossbills further benefit from social information gathered from observing other food restricted red crossbills in both seasons. Observed changes in body mass were only partially explained by seasonal differences in food intake. Our results demonstrate seasonal acclimation to food stress and social information use across seasons in a controlled captive environment and highlight the importance of considering diverse physiological systems (e.g., thermogenic, metabolic, digestive, etc) to understand organismal responses to environmental challenges.

Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Viral Hepatitis: The Interlink.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one-third of the global population and has become the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) remain significant challenges to liver health even in the 21st century. The co-existence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. A thorough understanding of the pathobiological interactions between MAFLD and these two chronic viral infections is crucial for appropriately managing these patients. In this comprehensive clinical review, we discuss the various mechanisms of chronic viral hepatitis-mediated metabolic dysfunction and the impact of MAFLD on the progression of liver disease.

Early flexible endoscopic evaluation of swallowing after mechanical thrombectomy in stroke patients.

OBJECTIVE: The aims of the study were to (1) characterize the findings of flexible endoscopic evaluation of swallowing (FEES) in stroke patients undergoing mechanical thrombectomy (MT); (2) analyse the screening performance of the Standardized Swallowing Assessment (SSA); and (3) study the impact of FEES-defined dysphagia on 3-month outcomes. METHODS: This single-centre study was based on a local registry of consecutive acute ischaemic stroke patients undergoing MT during a 1-year period. Patients received FEES within 5 days of admission regardless of the result of dysphagia screening. We compared baseline demographic and clinical characteristics of patients with and without FEES-defined dysphagia. We collected 3-month modified Rankin Scale (mRS) and individual index values of the European Quality of Life 5 Dimensions (EQ-5D-iv). Using univariable and multivariable regression analyses we predicted 3-month outcomes for presence of dysphagia and for FEES-defined dysphagia severity. RESULTS: We included 137 patients with a median age of 74 years, 43.1% were female, median NIHSS was 12 and successful recanalization was achieved in 92.7%. Stroke-associated pneumonia occurred in 8% of patients. FEES-defined dysphagia occurred in 81% of patients. Sensitivity of the SSA as a dysphagia screening was 67%. Presence of dysphagia and increasing severity of dysphagia were independently associated with increasing 3-month mRS score. Increasing dysphagia severity dysphagia was independently associated with lower EQ-5D-iv. INTERPRETATION: Early FEES-defined dysphagia occurs in four in every five patients undergoing MT. SSA has a suboptimal dysphagia screening performance. Presence of dysphagia and increasing dysphagia severity predict worse functional outcome and worse health-related quality-of-life.

Lateral Approach to the Cervical Spine to Manage Degenerative Cervical Myelopathy and Radiculopathy.

BACKGROUND: The cervical lateral approach can enlarge the spinal canal and foramen to achieve an effective neural decompression without needing spine stabilization. For this review, the authors' main objective was to illustrate the rationale, advantages, disadvantages, complications, and pitfalls of this technique, highlighting also areas for future development. MATERIALS AND METHODS: A Medline via PubMed database search was carried out by using both keywords, namely "cervical oblique corpectomy," "multilevel oblique corpectomy and foraminotomy," and "lateral vertebrectomy," and Medical Subject Headings (MeSH) terms from 1 January 1991, up to 31 December 2021. RESULTS: The analyzed articles suggested that the use of such a technique has declined over time; only 29 clinical studies met all the inclusion criteria and were retained for data analysis, including 1200 patients undergoing such an approach for the management of degenerative cervical myelopathies (DCMs) or of radiculopathies. The main etiopathogeneses were cervical stenosis, degenerative disk disease, or a mix of them-78% of which had a favorable outcome; the most frequent complications were transient and permanent Horner syndrome in 13.6% and 9.2% of cases, respectively. Long-term stability was reported in 97% of patients. CONCLUSION: Multilevel cervical oblique vertebrectomy and/or lateral foraminotomy allow wide neural structure decompression and optimal stability given that the physiological spinal motion is preserved.

Stewardship-Guided T2Candida Testing Shortens Time to Antifungal Treatment and Reduces Antifungal Usage Among Medical Intensive Care Unit Patients With Septic Shock.

Background: Diagnosis of invasive candidiasis (IC) is limited by insensitivity and slow turnaround of cultures. Our objectives were to define the performance of T2Candida, a nonculture test, under guidance of a diagnostic stewardship program, and evaluate impact on time to antifungal initiation and antifungal utilization. Methods: This was a retrospective study of adult medical intensive care unit (MICU) patients with septic shock for whom T2Candida testing was performed from March 2017 to March 2020. Patients with positive T2Candida results during this period were compared to MICU patients who did not undergo T2Candida testing but had septic shock and blood cultures positive for Candida from January 2016 through March 2020. Results: Overall, 155 T2Candida tests from 143 patients were included. Nine percent of T2Candida tests were positive compared to 4.5% of blood cultures. Sensitivity, specificity, positive predictive value, and negative predictive value of T2Candida for proven and probable IC were 78%, 95%, 50%, and 99%, respectively. Patients who tested positive for T2Candida (n = 14) were diagnosed earlier and initiated on antifungal therapy sooner than patients with IC (n = 14) diagnosed by blood culture alone (median, 5.6 vs 60 hours; P < .0001). Median antifungal days of therapy/1000 patient-days were 23.3/month preimplementation and 15/month postimplementation (P  = .007). Following a negative T2Candida result, empiric antifungals were either not administered in 58% or discontinued within 72 hours in 96% of patients. Conclusions: Diagnostic stewardship guided T2Candida testing resulted in reduced time to IC diagnosis, faster initiation of antifungal therapy, and lower antifungal usage among MICU patients with septic shock.

Comparison of Fluid Replacement with Sterofundin ISO® vs. Deltajonin® in Infants Undergoing Craniofacial Surgery-A Retrospective Study.

In recent decades, infusion solutions such as NaCl 0.9% and lactate Ringer's solution have been replaced in clinical practice. Since 2017, the national guidelines for perioperative infusion therapy in children recommend balanced isotonic solutions to maintain fluid balance. The composition of balanced infusion solutions varies with respect to their electrolyte content. Hyperchloremia may be mistaken for hypovolemia and may interfere with volume therapy in pediatric patients. Sterofundin ISO® balanced solution contains 127 mmol/L chloride and may cause hyperchloremic acidosis if administered in large volumes. OBJECTIVES: The purpose of this study was to compare the effects of Sterofundin ISO® (SF) therapy with the balanced isochloremic solution Deltajonin® (DJ) (106 mmol/L chloride) on the acid-base status in infants undergoing craniofacial surgery. METHODS: This retrospective, non-blinded study included 100 infants undergoing craniectomy due to isolated nonsyndromic sagittal craniosynostosis. The first 50 infants received Sterofundin ISO®. Due to changes in national guidelines, the infusion was changed to the isoionic Deltajonin® in an additional 50 infants in 2017. Pre- and postoperative values of chloride, pH, base excess, bicarbonate, and albumin and phosphate were determined, and the strong-ion difference, strong-ion gap, anion gap, and weak acids were calculated. RESULTS: Both groups were comparable in terms of their age, sex, underlying disease, preoperative electrolytes (except K at 3.9 ± 0.3 mmol/L (SF) vs. 4.1 ± 0.3 mmol/L (DJ) and lactate 8.7 ± 2.1 (SF) vs. 9.6 ± 2.6 mmol/L (DJ)). In the Sterofundin ISO® group, hyperchloremic metabolic acidosis was observed in 19 patients, whereas only 2 infants in the Deltajonin® group had hyperchloremic metabolic acidosis. The postoperative chloride level was 111 ± 2.7 mmol/L (SF) vs. 108 ± 2.4 mmol/L (DJ). The difference in anion gap was 12.5 ± 3.0 mmol/L (SF) vs. 14.6 ± 2.8 mmol/L (DJ), and the difference in SIDa (apparent strong-ion difference) was 30.9 mmol/L (SF) vs. 33.8 mmol/L (DJ). CONCLUSIONS: Hyperchloremic acidosis can be induced by the volume replacement with high-chloride-concentration crystalloids such as Sterofundin ISO®. This can be detected using the Stewart model.

The Effect of a Bacillus Probiotic and Essential Oils Compared to an Ionophore on the Rumen Microbiome Composition of Feedlot Cattle.

The rising concern of antibiotic growth promoter use in livestock has necessitated the investigation into alternative feed additives. The effect of a probiotic and essential oils to an ionophore on the rumen microbiome composition of Bonsmara bulls raised under feedlot conditions was compared. Forty-eight Bonsmara weaners were allocated to four groups: a group with basal diet (CON) and three groups supplemented with monensin (MON), probiotic (PRO), and essential oils (EO). During the 120 days feeding period, rumen content was collected from four animals per group within each phase via a stomach tube for 16S rRNA and internal transcribed spacer (ITS) sequencing as well as volatile fatty acid analysis. In the starter phase, MON had a significantly lower acetate to propionate ratio and a higher Succinivibrionaceae abundance. The abundance of Lachnospiraceae was significantly higher in EO compared to MON. In the finisher phase, PRO had a significantly higher bacterial diversity. The alpha diversity did not differ between the fungal populations of the groups. The abundance of Proteobacteria was the lowest in PRO compared to the other groups. Limited variation was observed between the rumen microbiome composition of monensin compared to the other treatment groups, indicating that these alternatives can be considered.

Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures.

The longstanding model is that most bloodstream infections (BSIs) are caused by a single organism. We perform whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrate that BCs contain mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibit phenotypes that are potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identify mixed fluconazole-susceptible and -resistant populations. Diversity in drug susceptibility is likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants are fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a population-based model of C. glabrata genotypic and phenotypic diversity during BSIs.

Through the orbit and beyond: Current state and future perspectives in endoscopic orbital surgery on behalf of the EANS frontiers committee in orbital tumors and the EANS skull base section.

Introduction: Orbital surgery has always been disputed among specialists, mainly neurosurgeons, otorhinolaryngologists, maxillofacial surgeons and ophthalmologists. The orbit is a borderland between intra- and extracranial compartments; Krönlein's lateral orbitotomy and the orbitozygomatic infratemporal approach are the historical milestones of modern orbital-cranial surgery. Research question: Since its first implementation, endoscopy has significantly impacted neurosurgery, changing perspectives and approaches to the skull base. Since its first application in 2009, transorbital endoscopic surgery opened the way for new surgical scenario, previously feasible only with extensive tissue dissection. Material and methods: A PRISMA based literature search was performed to select the most relevant papers on the topic. Results: Here, we provide a narrative review on the current state and future trends in endoscopic orbital surgery. Discussion and conclusion: This manuscript is a joint effort of the EANS frontiers committee in orbital tumors and the EANS skull base section.

The relationship between neurogenic dysphagia, stroke-associated pneumonia and functional outcome in a cohort of ischemic stroke patients treated with mechanical thrombectomy.

INTRODUCTION: Mechanical thrombectomy (MT) is an established treatment approach in acute ischemic stroke patients with large vessel occlusion (LVO). Recent studies suggest that the prevalence of dysphagia and pneumonia risk is increased in this patient population. The aim of this study was to systematically evaluate the prevalence, predictors, and influence of neurogenic dysphagia for 3-month outcome in a large population of patients receiving MT and to elucidate the relationship between dysphagia, stroke-associated pneumonia (SAP) and medium-term functional outcome. MATERIALS AND METHODS: Data of a prospective collected registry of patients with LVO and MT between 2016 and 2019 were analyzed retrospectively. Binary logistic regression was carried out to determine predictors for dysphagia and 3-month outcome as measured by the modified Rankin Scale, respectively. A mediation analysis was performed to investigate the mediating influence of intercurrent SAP. RESULTS: A total of 567 patients were included in the study. Mean age was 73.4 years, 47.8% of the patients were female, and median NIHSS was 15.0. The prevalence of dysphagia was 75.1% and 23.3% of all patients developed SAP. In the regression analysis, dysphagia was one of the main independent predictors for poor functional outcome at 3 months. The mediator analysis revealed that the effect of dysphagia on the functional outcome at 3 months was not mediated by the occurrence of SAP. DISCUSSION: The prevalence of dysphagia is high and exerts both negative short- and medium-term effects on patients with large vessel occlusion who undergo MT.

Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections.

BACKGROUND: The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. This guidance document focuses on infections caused by extended-spectrum ß-lactamase producing Enterobacterales (ESBL-E), AmpC ß-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document. METHODS: A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR-P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. RESULTS: Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are also discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults. CONCLUSIONS: The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial resistant infections. This document is current as of December 31, 2022 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/.

Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures.

The longstanding paradigm is that most bloodstream infections (BSIs) are caused by a single organism. We performed whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrated that BCs contained mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibited phenotypes that were potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identified mixed fluconazole-susceptible and â€"resistant populations. Diversity in drug susceptibility was likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants were fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a new population-based paradigm of C. glabrata genotypic and phenotypic diversity during BSIs.

Risk factors for progression of chronic kidney disease: An investigation in prepubertal children.

AIM: Previous studies on progression of chronic kidney disease (CKD) in children have included older post-pubertal subjects. This study attempted to evaluate risk factors for progression of CKD in pre-pubertal children. METHODS: An observational study of children aged 2-10 years with an eGFR within the limits of >30 and <75 mL/min/1.73 m2 was performed. Presenting clinical and biochemical risk factors, as well as diagnosis, were analysed for their association with progression to kidney failure, time to kidney failure and for the rate of decline of kidney function. RESULTS: One hundred and twenty-five children were studied of whom 42 (34%) had progressed to CKD stage 5 during the median period of follow up of 3.1 (IQR = 1.8-6) years. Hypertension, anaemia and acidosis at entry were associated with progression but they did not predict reaching the end point. Only glomerular disease, proteinuria and stage 4 kidney disease were independent predictors of kidney failure and the time to kidney failure. The rate of kidney function decline was greater in patients with glomerular than non-glomerular disease. CONCLUSIONS: Common modifiable risk factors, when present at initial evaluation, were not independently associated with CKD progression to kidney failure in prepubertal children. Only non-modifiable risk factors and proteinuria predicted eventual stage 5 disease. The physiological changes of puberty may be the major precipitator of kidney failure during adolescence.

Biofidelic image registration for head and neck region utilizing an in-silico articulated skeleton as a transformation model.

Objective.We propose an integration scheme for a biomechanical motion model into a deformable image registration. We demonstrate its accuracy and reproducibility for adaptive radiation therapy in the head and neck region.Approach. The novel registration scheme for the bony structures in the head and neck regions is based on a previously developed articulated kinematic skeleton model. The realized iterative single-bone optimization process directly triggers posture changes of the articulated skeleton, exchanging the transformation model within the deformable image registration process. Accuracy in terms of target registration errors in the bones is evaluated for 18 vector fields of three patients between each planning CT and six fraction CT scans distributed along the treatment course.Main results. The median of target registration error distribution of the landmark pairs is 1.4 ± 0.3 mm. This is sufficient accuracy for adaptive radiation therapy. The registration performs equally well for all three patients and no degradation of the registration accuracy can be observed throughout the treatment.Significance. Deformable image registration, despite its known residual uncertainties, is until now the tool of choice towards online re-planning automation. By introducing a biofidelic motion model into the optimization, we provide a viable way towards an in-build quality assurance.

Flavin Charge Redistribution upon Optical Excitation Is Independent of Solvent Polarity.

Flavin absorption spectra encode molecular details of the flavin's local environment through coupling of local electric fields with the chromophore's charge redistribution upon optical excitation. Translating experimentally measured field-tuned transition energies to local electric field magnitudes and directions across a wide range of field magnitudes requires that the charge redistribution be independent of the local field. We have measured the charge redistribution upon optical excitation of the derivatized flavin TPARF in the non-hydrogen-bonding, nonpolar solvent toluene, with and without a tridentate hydrogen-bonding ligand, DBAP, using electronic Stark spectroscopy. These measurements were interpreted using TD-DFT finite field and difference density calculations. In comparing our present results to previous Stark spectroscopic analyses of flavin in more polar solvents, we conclude that flavin charge redistribution upon optical excitation is independent of solvent polarity, indicating that dependence of flavin transition energies on local field magnitude is linear with local field magnitude.