Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2- early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2- trial.

BACKGROUND: In high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy versus solvent-based (sb)-paclitaxel in neoadjuvant trials; however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection. PATIENTS AND METHODS: Within the WSG-ADAPT trial (NCT01779206), high-risk HR+/HER2- EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m2 q2w or 8× nab-paclitaxel 125 mg/m2 q1w, followed by 4× epirubicin + cyclophosphamide (90 mg + 600 mg) q2w; inclusion criteria: (i) cN0-1, RS 12-25, and post-ET Ki67 >10%; (ii) cN0-1 with RS >25. Patients with cN2-3 or (G3, baseline Ki67 ≥40%, and tumor size >1 cm) were allowed to be included without RS and/or ET response testing. Associations of key factors with pathological complete response (pCR) (primary) and survival (secondary) endpoints were analyzed using statistical mediation and moderation models. RESULTS: Eight hundred and sixty-four patients received neoadjuvant nab-paclitaxel (n= 437) or sb-paclitaxel (n = 427); nab-paclitaxel was superior for pCR (20.8% versus 12.9%, P = 0.002). pCR was higher for RS >25 versus RS ≤25 (16.0% versus 8.4%, P = 0.021) and for ET non-response versus ET response (15.1% versus 6.0%, P = 0.027); no factors were predictive for the relative efficacy of nab-paclitaxel versus sb-paclitaxel. Patients with pCR had longer distant disease-free survival [dDFS; hazard ratio 0.42, 95% confidence interval (CI) 0.20-0.91, P = 0.024]. Despite favorable prognostic association of RS >25 versus RS ≤25 with pCR (odds ratio 3.11, 95% CI 1.71-5.63, P ≤ 0.001), higher RS was unfavorably associated with dDFS (hazard ratio 1.03, 95% CI 1.01-1.05, P = 0.010). CONCLUSIONS: In high-risk HR+/HER2- EBC, neoadjuvant nab-paclitaxel q1w appears superior to sb-paclitaxel q2w regarding pCR. Combining RS and ET response assessment appears to select patients with highest pCR rates. The disadvantage of higher RS for dDFS is reduced in patients with pCR. These are the first results from a large neoadjuvant randomized trial supporting the use of RS to help select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- EBC.

The B-APNEIC score: distilling the STOP-Bang questionnaire to identify patients at high risk for severe obstructive sleep apnoea.

The STOP-Bang questionnaire is an established clinical screening tool to identify the risk of having mild, moderate or severe obstructive sleep apnoea using eight variables. It is unclear whether all eight variables contribute equally to the risk of clinically significant obstructive sleep apnoea. We analysed each variable for its contribution to detecting obstructive sleep apnoea; based on the results, we investigated whether the STOP-Bang questionnaire could be abbreviated to identify patients at high risk for severe obstructive sleep apnoea. We recruited patients with suspected obstructive sleep apnoea who were referred for overnight polysomnography. We used multivariable logistic regression to investigate the association of STOP-Bang parameters with severe obstructive sleep apnoea based on clinical and polysomnography data. Regression estimates were used to select variables to create the novel B-APNEIC score. We constructed receiver operating characteristic curves for the STOP-Bang questionnaire and B-APNEIC scores to identify patients with severe obstructive sleep apnoea and compared the areas under the curve using the DeLong method. Of the 275 patients enrolled, 32% (n = 88) had severe obstructive sleep apnoea. Logistic regression demonstrated that neck circumference (OR 2.20; 95%CI 1.10-4.40, p = 0.03) was the only variable independently associated with severe obstructive sleep apnoea. Observed apnoea during sleep, blood pressure and body mass index were the three next most closely trending predictors of severe obstructive sleep apnoea and were included along with neck circumference in the B-APNEIC score. Receiver operating curves demonstrated that the areas under the curve for STOP-Bang vs. B-APNEIC were comparable for identifying patients with severe obstructive sleep apnoea (OR 0.75; 95%CI 0.68-0.81 vs. OR 0.75; 95%CI 0.68-0.81: p = 0.99, respectively). Our results suggest that the B-APNEIC score is a simplified adaptation of the STOP-Bang questionnaire with equivalent effectiveness in identifying patients with severe obstructive sleep apnoea. Further studies are needed to validate and build on our findings.

International multicentre review of perioperative management and outcome for catecholamine-producing tumours.

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.

Comparison of the horizontal diameter to a modeled area of traction in eyes with vitreomacular traction: is the diameter close enough to the truth?

PURPOSE: In daily practice, vitreomacular traction (VMT) is described by the horizontal diameter of its attachment site implying a regular round shape of VMT. We investigated the deviation from this circular area of vitreous traction in patients with VMT. METHODS: A retrospective analysis of optical coherence tomography (OCT) scans was performed. The area of vitreomacular attachment was determined using six radial OCT scans (Ameasured). The assumed circular area of traction was calculated based on measuring the maximal horizontal diameter for comparison (Acircular). RESULTS: Thirty-seven eyes of 37 patients with pure VMT were included. Patients' mean age was 72.8 ± 8.2 years. Mean horizontal VMT diameter was 400.8 ± 230.5 µm (median 361 µm; range 44-991 µm). While there was no difference between mean areas of traction for Acircular and Ameasured (P = 0.93), the individual difference (|Acircular - Ameasured|) was 0.042 (± 0.044) mm2 in mean or relative 73.0% (± 135.8%). A difference of ≥ 30% of Ameasured to Acircular was found in 16 eyes (43.2%) and ≥ 100% in 7 eyes (18.9%), respectively. CONCLUSION: Vitreous attachment sites possess an irregular non-circular shape in a significant number of eyes with VMT. Consequently, the area of traction appears inaccurately described by its horizontal VMT diameter alone. As the area of traction is important for therapeutic recommendation, our results emphasize the need for a more precise description of the area of traction in eyes with VMT.

Moraxella catarrhalis induces CEACAM3-Syk-CARD9-dependent activation of human granulocytes.

The human restricted pathogen Moraxella catarrhalis is an important causal agent for exacerbations in chronic obstructive lung disease in adults. In such patients, increased numbers of granulocytes are present in the airways, which correlate with bacteria-induced exacerbations and severity of the disease. Our study investigated whether the interaction of M. catarrhalis with the human granulocyte-specific carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-3 is linked to NF-κB activation, resulting in chemokine production. Granulocytes from healthy donors and NB4 cells were infected with M. catarrhalis in the presence of different inhibitors, blocking antibodies and siRNA. The supernatants were analysed by enzyme-linked immunosorbent assay for chemokines. NF-κB activation was determined using a luciferase reporter gene assay and chromatin-immunoprecipitation. We found evidence that the specific engagement of CEACAM3 by M. catarrhalis ubiquitous surface protein A1 (UspA1) results in the activation of pro-inflammatory events, such as degranulation of neutrophils, ROS production and chemokine secretion. The interaction of UspA1 with CEACAM3 induced the activation of the NF-κB pathway via Syk and the CARD9 pathway and was dependent on the phosphorylation of the CEACAM3 ITAM-like motif. These findings suggest that the CEACAM3 signalling in neutrophils is able to specifically modulate airway inflammation caused by infection with M. catarrhalis.

Association of metabolic syndrome and surgical factors with pulmonary adverse events, and longitudinal mortality in bariatric surgery.

BACKGROUND: Postoperative pulmonary complications (PPC) in bariatric surgery have not been well studied. Additionally, many bariatric patients suffer from the metabolic syndrome (MetS), contributing to surgical risk. We examined the incidence of PPC and MetS in a large national bariatric database. Furthermore, we analysed the relationships between morbidity, mortality, PPC, MetS, and several other comorbidities and also surgical factors. METHODS: The Bariatric Outcomes Longitudinal Database (BOLD™) is a registry that includes up to 365 day outcomes. We analysed data between January 2008 and October 2010. The PPC tracked included pneumonia, atelectasis, pleural effusion, pneumothorax, adult respiratory distress syndrome, and respiratory failure. A composite pulmonary adverse event (CPAE) included the occurrence of any of these. MetS was defined as the combination of hypertension, dyslipidaemia, and diabetes mellitus. The association of MetS and additional comorbibities, procedural data, and patient characteristics with CPAEs was examined with appropriate statistical tests. RESULTS: A total of 158 405 patients had a low incidence of PPC (0.91%) and a low mortality (0.6%) after bariatric surgery. MetS was prevalent in 12.7%, and was a significant risk factor for CPAE and mortality. Age, BMI, ASA physical status classification, surgical duration, procedure type, MetS (P<0.001), and additional comorbidities were significantly associated with CPAEs. CONCLUSIONS: The incidence of PPC was low after bariatric surgery. Increasing age, BMI, ASA status, MetS, obstructive sleep apnoea, asthma, congestive heart failure, surgical duration, and procedure type were independently significantly associated with PPC. Pulmonary complications and MetS were significantly associated with increased postoperative mortality.

A micro RNA-146a polymorphism is associated with coronary restenosis.

The association of the miRNA-146a polymorphism rs2910164 with atherosclerosis and restenosis was investigated. We found no association with atherosclerosis; however, we found a negative association for the G/C (P = 0.007) and a positive association for the C/C genotype with the risk of restenosis, which is the main drawback for cardiac surgery.

A systematic review and meta-analysis of ketamine for the prevention of persistent post-surgical pain.

While post-operative pain routinely resolves, persistent post-surgical pain (PPSP) is common in certain surgeries; it causes disability, lowers quality of life and has economic consequences. The objectives of this systematic review and meta-analysis were to evaluate the effectiveness of ketamine in reducing the prevalence and severity of PPSP and to assess safety associated with its use. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE through December 2012 for articles in any language. We included randomized, controlled trials in adults in which ketamine was administered perioperatively via any route. Seventeen studies, the majority of which administered ketamine intravenously, met all inclusion criteria. The overall risk of developing PPSP was not significantly reduced at any time point in the ketamine group vs. placebo, nor did comparisons of pain severity scores reach statistical significance. Sensitivity analysis of exclusively intravenous ketamine studies included in this meta-analysis demonstrated statistically significant reductions in risk of developing PPSP at 3 and 6 months (P = 0.01 and P = 0.04, respectively). Adverse event rates were similar between ketamine and placebo groups. The study data from our review are heterogeneous and demonstrate efficacy of intravenously administered ketamine only in comparison with placebo. Highly variable timing and dosing of ketamine in these studies suggest that no unifying effective regimen has emerged. Future research should focus on clinically relevant outcomes, should stratify patients with pre-existing pain and possible central sensitization and should enroll sufficiently large numbers to account for loss to follow-up in long-term studies.

Plant macrofossil data for 48-0 ka in the USGS North American Packrat Midden Database, version 5.0.

Plant macrofossils from packrat (Neotoma spp.) middens provide direct evidence of past vegetation changes in arid regions of North America. Here we describe the newest version (version 5.0) of the U.S. Geological Survey (USGS) North American Packrat Midden Database. The database contains published and contributed data from 3,331 midden samples collected in southwest Canada, the western United States, and northern Mexico, with samples ranging in age from 48 ka to the present. The database includes original midden-sample macrofossil counts and relative-abundance data along with a standardized relative-abundance scheme that makes it easier to compare macrofossil data across midden-sample sites. In addition to the midden-sample data, this version of the midden database includes calibrated radiocarbon (14C) ages for the midden samples and plant functional type (PFT) assignments for the midden taxa. We also provide World Wildlife Fund ecoregion assignments and climate and bioclimate data for each midden-sample site location. The data are provided in tabular (.xlsx), comma-separated values (.csv), and relational database (.mdb) files.

[Current treatment strategies for vitreomacular traction and macular holes: a survey of retinal specialists in Germany]. / Update zur Behandlungsstrategie bei vitreomakulärer Traktion und Makulaforamen: eine Umfrage unter Retinologen in Deutschland.

BACKGROUND: To evaluate the different treatment strategies for eyes with vitreomacular traction (VMT) and macular holes (MF) regarding the indications and initiation of treatment. OBJECTIVE: The aim of this study is to facilitate clinical decision making by presenting the opinions of experienced retinal specialists in the context of the current literature and the changed approval situation for ocriplasmin. MATERIAL AND METHODS: Members of the German Retina Society (RG) were questioned in an online survey. Based on a literature review a 100-question questionnaire was created and sent to all members of the RG via an electronic link to the online platform "LimeSurvey". Voluntary participation was possible from 15 October 2021 to 15 November 2021. Data collection and statistical analysis were anonymized. RESULTS: The responses of the 115 participants were congruent with the presentation of the new S1 guidelines on this topic. The indications for active treatment of focal VMT without MF were postponed in favor of watchful waiting, with the individual symptoms of the patient playing a major role in the proposed temporal management. The results on the indications for vitrectomy are consistent and convincingly confirm the opinions on the efficacy and risk assessment of this therapeutic procedure. CONCLUSION: The results presented provide an overview of the consensus and controversies in the current treatment options for VMT and MF. With the help of a homogeneous and experienced group of retinal experts, it was possible to develop individual treatment strategies.

Radon Exposure and Incident Stroke Risk in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Little is known about the role of radon in the epidemiology of stroke among women. We therefore examined the association between home radon exposure and risk of stroke among middle-aged and older women in the United States. METHODS: We conducted a prospective cohort study of postmenopausal women aged 50-79 years at baseline (1993-1998) in the Women's Health Initiative. We measured exposures as 2-day, indoor, lowest living-level average radon concentrations in picocuries per liter (pCi/L) as estimated in 1993 by the US Geological Survey and reviewed by the Association of American State Geologists under the Indoor Radon Abatement Act. We used Cox proportional hazards models to estimate risk of incident, neurologist-adjudicated stroke during follow-up through 2020 as a hazard ratio and 95% CI, adjusting for study design and participant demographic, social, behavioral, and clinical characteristics. RESULTS: Among 158,910 women without stroke at baseline (mean age 63.2 years; 83% white), 6,979 incident strokes were identified over follow-up (mean 13.4 years). Incidence rates were 333, 343, and 349 strokes per 100,000 woman-years at radon concentrations of <2, 2-4, and >4 pCi/L, respectively. Compared with women living at concentrations <2 pCi/L, those at 2-4 and >4 pCi/L had higher covariate-adjusted risks of incident stroke: hazard ratio (95% CI) 1.06 (0.99-1.13) and 1.14 (1.05-1.22). Using nonlinear spline functions to model radon, stroke risk was significantly elevated at concentrations ranging from 2 to 4 pCi/L (p = 0.0004), that is, below the United States Environmental Protection Agency Radon Action Level for mitigation (4 pCi/L). Associations were slightly stronger for ischemic (especially cardioembolic, small vessel occlusive, and large artery atherosclerotic) than hemorrhagic stroke, but otherwise robust in sensitivity analyses. DISCUSSION: Radon exposure is associated with moderately increased stroke risk among middle-aged and older women in the United States, suggesting that promulgation of a lower Radon Action Level may help reduce the domestic impact of cerebrovascular disease on public health.

Association of vitamin D receptor gene polymorphisms with severe atopic dermatitis in adults.

BACKGROUND: Vitamin D mediates immunomodulatory functions, and beneficial functions in allergic diseases have been suggested. Vitamin D receptor gene (VDR) polymorphisms are known but have not been studied in patients with atopic dermatitis (AD). OBJECTIVES: To investigate the frequency of four common VDR gene polymorphisms in patients with AD, and their potential functional relevance. METHODS: In this case-control study, 265 patients with AD [n=142 severe AD, Scoring AD index (SCORAD) > 40; n=123 moderate AD, SCORAD 15-40] and 265 healthy controls were genotyped for four common VDR gene polymorphisms by restriction fragment length polymorphism analysis. The VDR haplotype sequences were analysed in silico. Baseline and activation-induced gene expression of VDR and the vitamin D metabolizing enzyme CYP24A1 were analysed in monocytes of homozygous VDR haplotype carriers by quantitative reverse transcription-polymerase chain reaction. RESULTS: In patients with severe AD, the VDR BsmI (rs1544410) G allele, ApaI (rs7975232) C allele and TaqI (rs731236) T alleles were over-represented compared with healthy controls. These single nucleotide polymorphisms (SNP) were tightly linked, and the VDR haplotype GCT was correlated with severe AD and complementary AAC with protection from AD. The VDR haplotype GCT region is evolutionarily conserved. The VDR FokI (rs2228570) SNP was not associated with AD. Baseline VDR expression in monocytes and short-term activation were haplotype independent. CONCLUSION: A specific VDR haplotype is more frequent in patients with severe AD. These data indicate that VDR contributes to the control of AD, e.g. by regulation of the epidermal barrier function and/or local immune response.

Chromovitrectomy and the vitreoretinal interface.

It still remains unclear to which extent the presence and the amount of retinal debris seen in internal limiting membrane (ILM) specimens harvested during macular surgery for macular holes or epiretinal membranes are related to the procedure of ILM peeling itself or to modifications of the surgical technique, such as application of vital dyes for visualization of the ILM, or to pathological conditions with epiretinal membrane formation at the vitreoretinal interface. The presence of cellular fragments on the retinal side of the removed ILM appears to be of multifactorial origin, and additional causes besides dye application need to be considered. However, morphological studies with evaluation of vital dyes are still of relevance and provide additional insights into the ultrastructure of the vitreoretinal interface and its interaction with adjuvants used during macular surgery. Chromovitrectomy is an emerging field in vitreoretinal surgery. It is of importance to better understand the tissue-dye interactions, which not only alter the mechanical properties of the tissue being stained, but may also have an impact on the functional result postoperatively.

[Regression of idiopathic epiretinal membrane-Case report and consideration of the possible mechanism]. / Regression einer idiopathischen epiretinalen Gliose ­ Kasuistik und Überlegungen zum Mechanismus.

In the presence of a symptomatic epiretinal gliosis, pars plana vitrectomy with membrane peeling to remove the membrane is usually indicated in clinical practice. According to common clinical experience, almost no independent regression of such an epiretinal membrane and thus healing of the pathology alone exists. Therefore, the unusual case of bilateral independent regression of idiopathic epiretinal gliosis and formation of a lamellar macular hole in a 73-year-old male patient is described. Considerations of the possible mechanism are presented based on the existing literature. These include separation of inflammatory versus noninflammatory membranes, possible separation of individual layers depending on the status of the posterior vitreous limiting membrane and also the possible action of proteolytic systems in the posterior vitreous region. Finally, the question arises, whether patients have to be informed about this fact before possible surgery.

[Real-life results of anti-VEGF treatment in fellow eyes with nAMD]. / Real-life-Ergebnisse der Anti-VEGF-Therapie bei nAMD der Partneraugen.

PURPOSE: Neovascular age-related macular degeneration (nAMD) often affects both eyes. This study compared real-life outcomes of the first affected eye (1st eye) and the last affected eye (2nd eye) after anti-vascular endothelial growth factor (anti-VEGF) treatment. MATERIAL AND METHODS: For this retrospective monocenter study 3217 eyes from 2793 patients with nAMD were identified, who received at least 3 anti-VEGF injections between 2006 and 2014 at the University Eye Hospital of Munich. Included in the study were patients with bilateral nAMD when the 1st and 2nd eyes were not previously treated and there was a strict adherence with continuous follow-up for at least 5 years. Corrected visual acuity, number of intravitreal injections and visits as well as central macular thickness were compared. RESULTS: A total of 72 eyes of 36 patients were included in this analysis. Before anti-VEGF therapy, the group of 2nd eyes showed significantly better mean visual acuity than the 1st eyes (p < 0.001). This difference in visual acuity between 1st and 2nd eyes was noted at all time points throughout the follow-up period (p < 0.05). The mean number of cumulative injections was higher in the group of 2nd eyes (p = 0.04) with a comparable number of visits between both groups. In more than half of all patients the 2nd eye became affected by nAMD within 12 months following treatment initiation of the 1st eye and the majority (83%) followed within 3 years. CONCLUSION: In unilateral nAMD, regular monitoring of the fellow eye is essential to avoid severe bilateral vision loss. Early diagnosis with rapid initiation of treatment can preserve visual acuity and quality of life.

Single-dose intravenous paracetamol or propacetamol for prevention or treatment of postoperative pain: a systematic review and meta-analysis.

Paracetamol is the most commonly prescribed analgesic for the treatment of acute pain. The efficacy and safety of i.v. formulations of paracetamol is unclear. We performed a systematic search (multiple databases, bibliographies, any language, to May 2010) for single-dose, randomized, controlled clinical trials of propacetamol or i.v. paracetamol for acute postoperative pain in adults or children. Thirty-six studies involving 3896 patients were included. For the primary outcome, 37% of patients (240/367) receiving propacetamol or i.v. paracetamol experienced at least 50% pain relief over 4 h compared with 16% (68/527) receiving placebo (number needed to treat=4.0; 95% confidence interval, 3.5-4.8). The proportion of patients in propacetamol or i.v. paracetamol groups experiencing at least 50% pain relief diminished over 6 h. Patients receiving propacetamol or paracetamol required 30% less opioid over 4 h and 16% less opioid over 6 h than those receiving placebo. However, this did not translate to a reduction in opioid-induced adverse events (AEs). Similar comparisons between propacetamol or i.v. paracetamol and active comparators were either not statistically significant, not clinically significant, or both. AEs occurred at similar rates with propacetamol or i.v. paracetamol and placebo. However, pain on infusion occurred more frequently in those receiving propacetamol compared with placebo (23% vs 1%). A single dose of either propacetamol or i.v. paracetamol provides around 4 h of effective analgesia for about 37% of patients with acute postoperative pain. Both formulations are associated with few AEs, although patients receiving propacetamol have a higher incidence of pain on infusion.

[Biomarkers in full-thickness and lamellar defects of the macula]. / Biomarker bei durchgreifenden und lamellären Defekten der Makula.

BACKGROUND: Biomarkers are characteristic biological measurable signs and objective parameters to detect the state of health. Besides functional and temporal factors, imaging biomarkers play an increasingly important role. In full-thickness and lamellar defects of the macula numerous imaging parameters have been described. This knowledge resulted in new classifications for both clinical pictures, which are based on important biomarkers of these clinical pictures and characteristic features of described subtypes. METHODS: Imaging biomarkers for full-thickness and lamellar macular defects are described with respect to the classification and their functional prognostic importance. The importance of these biomarkers is presented. RESULTS: The current classification of full-thickness and lamellar macular defects is based on structural biomarkers. Biomarkers are important for prognostic and therapeutic evaluation and they have an impact on the surgical strategy. There are various surgical strategies for treatment of full-thickness macular holes depending on the size of the foramen and other biomarkers. The inverted ILM flap technique improves the closure rate of large macular holes. In lamellar macular holes showing signs of progression an early surgical intervention results in a good anatomical and functional prognosis. CONCLUSION: Multimodal diagnostics provide important preoperative, intraoperative, and postoperative features for macular holes and lamellar macular holes, which are essential biomarkers for the exact classification, the therapeutic strategy and for assessment of the prognosis.

[Optical coherence tomography biomarkers in epimacular membranes and vitreomacular traction syndrome]. / Optische Kohärenztomographie-Biomarker bei epimakulären Membranen und vitreomakulärem Traktionssyndrom.

Using high-resolution imaging, such as optical coherence tomography (OCT), the different layers of the retina as well as the vitreoretinal interface and its alterations can be very clearly differentiated. This includes the morphological characteristics of tractive maculopathies, such as epiretinal gliosis and vitreomacular traction syndrome. Additionally, structural alterations of the various layers of the neurosensory retina as a result of traction due to these pathologies can be demarcated. The latter have been investigated in clinical trials and evaluated as OCT biomarkers with respect to their prognostic and predictive value. In this review we would like to present and discuss various OCT biomarkers in the context of epimacular membranes and vitreomacular traction syndrome.

Use of Helmet CPAP in COVID-19 - A practical review.

Helmet CPAP (H-CPAP) has been recommended in many guidelines as a noninvasive respiratory support during COVID-19 pandemic in many countries around the world. It has the least amount of particle dispersion and air contamination among all noninvasive devices and may mitigate the ICU bed shortage during a COVID surge as well as a decreased need for intubation/mechanical ventilation. It can be attached to many oxygen delivery sources. The MaxVenturi setup is preferred as it allows for natural humidification, low noise burden, and easy transition to HFNC during breaks and it is the recommended transport set-up. The patients can safely be proned with the helmet. It can also be used to wean the patients from invasive mechanical ventilation. Our article reviews in depth the pathophysiology of COVID-19 ARDS, provides rationale of using H-CPAP, suggests a respiratory failure algorithm, guides through its setup and discusses the issues and concerns around using it.