The effects of sugammadex vs. neostigmine on postoperative respiratory complications and advanced healthcare utilisation: a multicentre retrospective cohort study.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation < 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

Does the identification of seniors at risk (ISAR) score effectively select geriatric patients on emergency admission?

The number of older patients admitted to emergency departments (ED) increases continuously. The Identification of Seniors at Risk (ISAR) score is currently recommended to screen patients in German ED, but its appropriateness is being criticized. ISAR scores and clinical characteristics from 98 emergency admissions (EA), 80 from acute geriatrics (AG) and 89 from a geriatric rehabilitation (GR) unit were compared retrospectively. No significant differences were found between groups, being the ISAR score positive in 87.7% of EA, 94.9% of AG and 94.4% of GR cases. None of positively identified geriatric patients in the EA was transferred to the geriatric ward of competence. EA patients showed significantly higher number of functional impairments (p = 0.001) and higher BI score (p < 0.0001) compared to AG and GR groups. A higher ISAR score threshold and additional functional information might be needed to better select patients in need of prompt treatment by a geriatric team.

Do independent geriatric outpatients with nocturnal polyuria profit from desmopressin?

OBJECTIVE: To compare the efficacy of desmopressin and placebo in independent geriatric outpatients with nocturnal polyuria (NP). METHODS: A prospective, randomized, single-center, national, double blind, placebo-controlled, fixed-dose, parallel group comparative trial was carried out. The study included 110 geriatric outpatients, 55 patients per treatment group using desmopressin acetate nasal spray (strength: 0.1 mg/ml) once daily of 10 µg/spray blast or placebo. MEASUREMENT: The NP positive geriatric outpatients with >33% nocturnal urine output volume, antidiuretic hormone (ADH) positive or negative were treated over 10 days with intranasal spray in the evening time (7 p.m.), drug or placebo. On day 1 voiding frequency, voiding volumes day and night, serum osmolarity and arginine-vasopressin (AVP) were measured at 7 p.m. On days 2, 5 and 10 creatinine, blood urea nitrogen (bun), blood count and C­reactive protein (CrP), vena cava diameter and bioimpedance were measured and a structured interview was implemented (voiding frequency, sleeping behavior and subjective and cognitive behavior). RESULTS: The NP patients showed a mean night voiding volume of 50.60%, 39.21% (n = 102) showed a low AVP level at baseline with no correlation to sodium concentration or voiding frequencies. The primary efficacy criterion, a decrease of the nocturnal voiding frequency during the course of the clinical trial as change from baseline at day 10 (visit 4) was 50% versus 41.40% in the verum versus placebo group, respectively but the differences were not significant. The U­test showed superiority of AVP-positive NP patients to a positive reaction on desmopressin. Sleeping time hours increased in both groups without significant differences. CONCLUSION: In this 10-day clinical trial desmopressin was not proven to be therapeutically superior to placebo with respect to micturition frequency or sleeping hours. Independent geriatric outpatients with decreased ADH levels seemed to respond and benefit from active treatment with desmopressin. The unexpected results in the placebo group may be due to the effect of intensive outpatient care and information on NP outpatients with normal AVP levels.

Dysregulated autophagy in restrictive cardiomyopathy due to Pro209Leu mutation in BAG3.

Myofibrillary myopathies (MFM) are hereditary myopathies histologically characterized by degeneration of myofibrils and aggregation of proteins in striated muscle. Cardiomyopathy is common in MFM but the pathophysiological mechanisms are not well understood. The BAG3-Pro209Leu mutation is associated with early onset MFM and severe restrictive cardiomyopathy (RCM), often necessitating heart transplantation during childhood. We report on a young male patient with a BAG3-Pro209Leu mutation who underwent heart transplantation at eight years of age. Detailed morphological analyses of the explanted heart tissue showed intracytoplasmic inclusions, aggregation of BAG3 and desmin, disintegration of myofibers and Z-disk alterations. The presence of undegraded autophagosomes, seen by electron microscopy, as well as increased levels of p62, LC3-I and WIPI1, detected by immunohistochemistry and western blot analyses, indicated a dysregulation of autophagy. Parkin and PINK1, proteins involved in mitophagy, were slightly increased whereas mitochondrial OXPHOS activities were not altered. These findings indicate that altered autophagy plays a role in the pathogenesis and rapid progression of RCM in MFM caused by the BAG3-Pro209Leu mutation, which could have implications for future therapeutic strategies.

A family of secreted pathogenesis-related proteins in Candida albicans.

Analysing culture supernatants of yeast and hyphal cells of Candida albicans, we found two close homologues of pathogenesis-related (PR-) 1 proteins, Rbe1p and Rbt4p, in the secretome. Due to sequence homology, three additional, yet not characterized open reading frames, ORF19.6200, ORF19.2787 and ORF19.2336, together with RBE1 and RBT4 were assigned to a novel family of CaPRY proteins. In a Δrbe1/Δrbt4 deletion strain, genome-wide transcriptional analysis revealed differential transcription of only a limited set of genes implicated in virulence and oxidative stress response. Single deletion of RBE1 or RBT4 in a clinical C. albicans isolate resulted in a moderate but significant attenuation in virulence in a mouse model for disseminated candidiasis. However, a synergistic effect was observed in a Δrbe1/Δrbt4 double deletion strain, where virulence was strongly affected. Remarkably, transcription of RBT4 and RBE1 was each upregulated in blastospores of Δrbe1 or hyphae of Δrbt4 deletion strains respectively, indicating functional complementation thereby compensating a potential virulence defect in the single deletion strains. Furthermore, the double deletion strain showed increased sensitivity to attack by polymorphonuclear leucocytes. Therefore, the crucial contribution of both C. albicans pathogenesis-related proteins to virulence might be vested in protection against phagocyte attack.

[Rehabilitation following total knee replacement. Conservative orthopedics and sport science]. / Anschlussheilbehandlung nach Knietotalendoprothesenimplantation. Konservative Orthopädie und Sportwissenschaft.

Total knee replacement (TKR) is a highly standardized procedure. However; many patients are not satisfied with the functional results. Surgery focuses initially on restoration of joint function. Based on the ICF classification (WHO) rehabilitation adds individual and social perspectives. The focus is not limited to body functions but includes abilities and participation. After surgery the patient suffers from pain, swelling, restricted blood circulation and a dramatic impairment of motor function. To prepare patients for activities of daily living it is important to analyze and understand the demands after TKR. Key qualities are the range of motion of the knee joint, functional joint stability, postural stability and muscle coordination. The paper describes a comprehensive rehabilitation protocol which is mainly based on the concept of functional training which consists of purposeful training preparing patients for activities of daily living and participation. It attempts to focus on multijoint movement as much as possible using closed chain muscle action (leg press, indoor cycling, gait training) and on sensorimotor training. A second focus is on postural stability (balance training). For clinical evaluation standardized scores are widely used (e.g. knee society score, HSS score). These scores were adapted for evaluation of the rehabilitation process (e.g. Staffelstein score, EVA-Reha score). However; these are not specific enough to analyze the effects of sensorimotor training and balance training. More detailed assessments should be used to evaluate the benefits of functional based rehabilitation concepts.

[Psychosomatic aspects in orthopedics]. / Psychosomatische Aspekte in der Orthopädie.

Psychosomatic disease patterns are a common differential diagnosis for orthopedic symptoms. Furthermore, mental factors, such as the method of disease processing or mental comorbidities, such as depression or somatization disorders have a great influence on the chronification of orthopedic complaints and the outcome following orthopedic interventions. The aim of this article is to present the psychosomatic pathomechanisms and disease patterns relevant for orthopedics and to derive recommendations for physician-patient communication, diagnostics, therapy and assessment.

Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis.

OBJECTIVES: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. MATERIALS AND METHODS: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. RESULTS: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (1.27 to 5.31) and 3.00 (1.22 to 7.89), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (OR 4.56, 1.56 to 14.87). CLINICAL SIGNIFICANCE: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis.

Vacuolar/lysosomal proteolysis: proteases, substrates, mechanisms.

Proteolysis is an essential post-transcriptional process. The lysosome/vacuole is the central organelle for non-specific proteolysis in eukaryotes. Most proteases that work in the lysosome enter it via the secretory pathway. The bulk of proteins to be degraded enter this proteolytic compartment via endocytosis and autophagocytosis. Our understanding of the mechanisms involved in these processes has increased considerably, and the information obtained in these studies has enabled new, specific proteolytic pathways to be investigated in other cellular compartments, particularly in the cytoplasm.

Chemo-Enzymatic Epoxidation of Lallemantia IbericaSeed Oil: Process Development and Economic-Ecological Evaluation.

The chemo-enzymatic epoxidation of Lallemantia iberica seed oil (LISO), a novel plant oil characterized by its exceptional high content of alpha-linolenic acid (> 60%), was developed using an immobilized lipase from Pseudozyma antarctica and hydrogen peroxide as oxidant. A statistical approach was used to study the effect of enzyme amount, temperature, time, and solvent amount on the oxirane oxygen content obtained during epoxidation. An oxirane oxygen content of 8.6 ± 0.2% corresponding to a yield of 82% was obtained under optimized conditions that were identified to be at an enzyme load of 8.2 g/mol of double bonds, a solvent amount of 56.4 wt.%, a temperature of 33 °C, and an incubation time of 17 h. In addition, the experimental investigation was combined with a techno-economic and ecological assessment gaining detailed information regarding cost structure and environmental impact for the chemo-enzymatic epoxidation of the novel plant oil.

[Involuntary patient admission and treatment against patient's will by emergency physicians]. / Zwangseinweisung und Zwangsbehandlung bei psychiatrischen Patienten als notärztliche Aufgabe.

INTRODUCTION: The treatment of acutely ill patients who presumably lack the insight or judgement to determine their need for medical treatment, is a difficult challenge for emergency physicians. We have carried out a study to assess the frequency and relevance of involuntary treatment and procedures in medical emergency services. METHODS: Retrospective chart analysis for a 1-year period was performed for all treatment protocols of a medical emergency service unit and for all court-ordered treatments of a guardianship court. Cases of involuntary treatment by emergency physicians were identified and analysed. RESULTS: In 10.4% of all emergency calls analysed a relevant and acute psychiatric condition was found. In 0.3% of the cases or 4.8% of the psychiatric cases, involuntary inpatient commitment was chosen by the emergency physician. DISCUSSION: Involuntary inpatient commitment by emergency physicians was only necessary in relatively few cases. Nevertheless, in order to be able to correctly consider treatment and management options, emergency physicians should be aware of the basic conditions for treatment without a patient's consent.

Primary stability of various forms of osteosynthesis in the treatment of fractures of the proximal tibia.

The treatment of fractures of the proximal tibia is complex and makes great demands on the implants used. Our study aimed to identify what levels of primary stability could be achieved with various forms of osteosynthesis in the treatment of diaphyseal fractures of the proximal tibia. Pairs of human tibiae were investigated. An unstable fracture was simulated by creating a defect at the metaphyseal-diaphyseal junction. Six implants were tested in a uniaxial testing device (Instron) using the quasi-static and displacement-controlled modes and the force-displacement curve was recorded. The movements of each fragment and of the implant were recorded video-optically (MacReflex, Qualysis). Axial deviations were evaluated at 300 N. The results show that the nailing systems tolerated the highest forces. The lowest axial deviations in varus and valgus were also found for the nailing systems; the highest axial deviations were recorded for the buttress plate and the less invasive stabilising system (LISS). In terms of rotational displacement the LISS was better than the buttress plate. In summary, it was found that higher loads were better tolerated by centrally placed load carriers than by eccentrically placed ones. In the case of the latter, it appears advantageous to use additive procedures for medial buttressing in the early phase.

Biogenesis of the yeast vacuole (lysosome). Active site mutation in the vacuolar aspartate proteinase yscA blocks maturation of vacuolar proteinases.

The activation process of vacuolar (lysosomal) proteinases in the yeast Saccharomyces cerevisiae is initiated by the PRA1 (PEP4) gene product, proteinase yscA. To elucidate the activation process of proteinase yscA the catalytically active amino acid Asp294 of the enzyme was exchanged with Ala294 using site directed mutagenesis. The resulting proteinase yscA-Ala294 showed no proteolytic activity against the substrate hemoglobin. The mutant protein did not undergo processing in vivo. This phenomenon is in good agreement with the hypothesis that maturation of proteinase yscA is due to self-processing of pro-proteinase yscA. Furthermore, proteinase yscA-Ala294 is not able to convert the zymogens pro-proteinase yscB and pro-carboxypeptidase yscY to the mature enzymes.

Identification of cell surface determinants in Candida albicans reveals Tsa1p, a protein differentially localized in the cell.

To identify cell surface proteins of Candida albicans, the predominant fungal pathogen in humans, we have established an approach using a membrane impermeable biotin derivative in combination with affinity purification. We were able to identify 29 different proteins under two distinct conditions. Among mannoproteins, heat shock proteins and glycolytic enzymes we found thiol-specific antioxidant-like protein 1 (Tsa1p) to be differentially localized depending on the conditions applied. Only in hyphally grown cells Tsa1p was localized to the cell surface whereas in blastospores no surface but mainly nuclear localization was found. This indicates that cell surface expression of at least some proteins is mediated by differential translocation.

Calcified plaque in the superior portion of the major fissure. An unusual manifestation of asbestos exposure.

Parietal pleural plaque is a well-recognized sign of exposure to asbestos. Visceral pleural involvement is an uncommon manifestation, and calcified visceral pleural plaques are rare. Those reported have been in the minor fissure and inferior major fissure. We describe a unique calcified plaque in the superior major fissure.

Relationships among premenstrual symptoms and menstrual cycle characteristics.

The severity of premenstrual syndrome symptoms has been described by different investigators as varying directly or inversely with the severity of dysmenorrhea. In a large population of women undergoing comprehensive psychological and medical evaluation for premenstrual syndrome complaints, the authors examined the relationship between menstrual cycle parameters and premenstrual syndrome. The severity of premenstrual symptoms varied directly with the severity of dysmenorrhea and premenstrual spotting but was not associated with any other menstrual cycle parameter. Multivariate analysis revealed that social and psychological variables are more strongly associated with variations in premenstrual symptoms than are any menstrual cycle parameters.

Bioavailability of nasally administered progesterone.

PIP: 8 healthy women volunteers between the ages of 22-38 participated in a study designed to explore the relationship between endogenous estradiol (E2) levels and progesterone (P) absorption. Physical and pelvic examinations and laboratory screening tests revealed no abnormalities. All women had regular menstrual cycles, at 24-32-day intervals, and all were free of a significant menstrual cycle symptoms. 2 studies were performed at least 72 hours apart in the follicular phase of the menstrual cycle. The following medications were administered in random order: nasal P (Pronasone), 20 mg and nasal P (Pronasone), 30 mg. Serum P levels were drawn at the following times: 0, 3, 6, 10, 20, 30, 60, 120, 180, 240, 360, and 480 minutes. Serum for E2 assay was taken from the 0 time sample. The women were examined with a nasal speculum after each nasal absorption study. Serum was separated and frozen for subsequent assay. The data were analyzed using the CLINFO system from the National Institutes of Health. All of the women complained of a mildly unpleasant taste within several minutes following Pronasone administration. No evidence of nasal irritation was observed in any woman. The similar absorption curves obtained with Pronasone 20 mg and 30 mg doses and the aberrantly high values and delayed peaks ob tained in 2 subjects with the 30 mg dose imply that further work on dosage range, ointment formulation, and the method of application may be necessary before dependable clinical utility can be demonstrated. The peak levels of P that were reached compare favorably with results using similar doses (25 mg) in cocoa butter rectal or vaginal suppositories but are somewhat lower than those seen with polyethylene glycol base suppositories. The apparent inverse relationship between serum E2 levels and P levels obtained with Pronasone in the 20-mg dose was not expected. Alterations of nasal vascularity, interstitial hydration, and mucous blanket production all might influence absorption. The study demonstrates that the intranasal route is a potentially useful approach for the administration of unmodified sex steroid medications and is likely to be clinically safe and acceptable to patients.^ieng