CT-defined sarcopenia predicts treatment response in primary central nervous system lymphomas.

OBJECTIVE: Body composition assessment derived from cross-sectional imaging has shown promising results as a prognostic biomarker in several tumor entities. Our aim was to analyze the role of low skeletal muscle mass (LSMM) and fat areas for prognosis of dose-limiting toxicity (DLT) and treatment response in patients with primary central nervous system lymphoma (PCNSL). METHODS: Overall, 61 patients (29 female patients, 47.5%) with a mean age of 63.8 ± 12.2 years, range 23-81 years, were identified in the data base between 2012 and 2020 with sufficient clinical and imaging data. Body composition assessment, comprising LSMM and visceral and subcutaneous fat areas, was performed on one axial slice on L3-height derived from staging computed tomography (CT) images. DLT was assessed during chemotherapy in clinical routine. Objective response rate (ORR) was measured on following magnetic resonance images of the head accordingly to the Cheson criteria. RESULTS: Twenty-eight patients had DLT (45.9%). Regression analysis revealed that LSMM was associated with objective response, OR = 5.19 (95% CI 1.35-19.94, p = 0.02) (univariable regression), and OR = 4.23 (95% CI 1.03- 17.38, p = 0.046) (multivariable regression). None of the body composition parameters could predict DLT. Patients with normal visceral to subcutaneous ratio (VSR) could be treated with more chemotherapy cycles compared to patients with high VSR (mean, 4.25 vs 2.94, p = 0.03). Patients with ORR had higher muscle density values compared to patients with stable and/or progressive disease (34.46 ± vs 28.18 ± HU, p = 0.02). CONCLUSIONS: LSMM is strongly associated with objective response in patients with PCNSL. Body composition parameters cannot predict DLT. CLINICAL RELEVANCE STATEMENT: Low skeletal muscle mass on computed tomography (CT) is an independent prognostic factor of poor treatment response in central nervous system lymphoma. Analysis of the skeletal musculature on staging CT should be implemented into the clinical routine in this tumor entity. KEY POINTS: • Low skeletal muscle mass is strongly associated with the objective response rate. • No body composition parameters could predict dose-limiting toxicity.

Fetoscopic laser coagulation for twin-to-twin transfusion syndrome: a comparison of flexible 1.0/1.2 mm fetoscopes with curved sheaths of 2.7/3.3 mm2 vs. 2 mm fetoscopic lens technique with sheaths of 6.6/11.3 mm2.

OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

Compassionate Othering: the construction of refugee patients in medical students' narratives - a qualitative study using story completion.

BACKGROUND: Refugees remain a marginalized population and are exposed to a variety of discriminatory processes, among them Othering which categorizes people as belonging or not-belonging according to certain ascribed characteristics. We explored how the narrative construction of refugee patients by medical students constitutes a form of Othering. METHODS: Using story completion, 124 5th year medical students at the Martin- Luther- University Halle-Wittenberg in October 2019 wrote a fictional story in response to a story stem situated in a medical practice. In a comparative approach, one patient presenting with abdominal pain lacks further characterization (version A) and the other is a refugee (version B). The stories were coded using qualitative content analysis by Mayring with a focus on content and narrative strategies (plot structure and perspective). RESULTS: We identified four themes: characters, medical condition, access to care and provision of substandard care. The stories were predominantly framed with a medical or an interaction-based plot structure and written from a process-oriented perspective. The themes in version B, supported by their use of narrative strategies, were largely contextualized within the patients' history of migration. An empathic depiction of patient B and the students' compassion for the patients facing substandard care were key motifs as well. CONCLUSION: The perception of the version B patients predominantly as refugees establishes their construction as an Other. The students' compassion acts as a representation of societal inequalities and remains an inept response without the tools to counter underlying discriminatory structures. Based on a discourse of deservingness, compassion alone therefore perpetuates Othering and highlights the need for structural competency training in medical school.

Pathways and Referral of Patients with Cancer in Rural Ethiopia: A Multi-center Retrospective Cohort Study.

INTRODUCTION: Well-organized patient pathways are essential to achieve early diagnosis and timely treatment of patients with cancer in Sub-Saharan Africa. This retrospective cohort study describes pathways and referral patterns of cancer patients in rural Ethiopia. PATIENTS AND METHODS: The retrospective study took place from October to December 2020 at 2 primary- and 6 secondary-level hospitals in southwestern Ethiopia. Of 681 eligible patients diagnosed with cancer between July 2017 and June 2020, 365 patients were included. Structured interviews on the patients' pathways were conducted by telephone. The primary outcome was successful referral, which was defined as occurring when the intended procedure was initiated at the receiving institution. Logistic regression was used to assess factors associated with successful referrals. RESULTS: Patients visited on average 3 health care institutions from their first encounter with a provider until their final treatment initiation. After diagnosis, only 26% (95) of patients were referred for further cancer treatment, of which 73% were successful. Patients referred for diagnostic tests were 10 times more likely to complete referrals successfully than patients referred for treatment. Overall, 21% of all patients remained without any therapy. CONCLUSION: We found that referral pathways of patients with cancer in rural Ethiopia were largely cohesive. The majority of patients referred for diagnostic or treatment services followed the advice. Nevertheless, an unacceptable number of patients remained without any treatment. Capacity for cancer diagnosis and treatment at primary- and secondary-level health facilities in rural Ethiopia must be expanded to enable early detection and timely care.

Validation of clinical-radiological scores for prognosis of mortality in acute pulmonary embolism.

INTRODUCTION: Acute pulmonary embolism (APE) is a hazardous disorder with a high mortality. Combination of clinical, radiological, and serological parameters can improve risk stratification of APE. Most of the proposed combined scores were not validated in independent cohorts. Our aim was to validate the proposed clinical-radiological scores for prognosis of 7- and 30-day mortality in APE. MATERIALS AND METHODS: Our sample comprised 531 patients with APE, mean age 64.8 ± 15.6 years, 221 (41.6%) females and 310 (58.4%) males. The following parameters were collected: Age and sex of the patients, mortality within the observation time of 30 days, simplified pulmonary embolism severity index (sPESI), pH troponin level (pg/ml), minimal systolic and diastolic blood pressures (mmHg), heart rate, O2 saturation, episodes of syncope, and need for vasopressors. On CT pulmonary angiography (CTPA), short axis ratio right ventricle/left ventricle (RV/LV), and reflux of contrast medium into the inferior vena cava were obtained. The following clinical-radiological scores were calculated: BOVA score, pulmonary embolism mortality score (PEMS), European Society of Cardiology (ESC) score, Kumamaru score, and Calgary acute pulmonary embolism (CAPE) score. RESULTS: Overall, 31 patients (5.8%) died within seven and 64 patients (12%) within 30 days. All scores showed high negative prognostic values ranging from 89.0 to 99.0%. PEMS and CAPE score demonstrated the highest specificity for 7-day mortality (93.4% and 85.0%), PEMS and BOVA for 30-day mortality (94.2% and 90.4%). The highest sensitivity was observed for ESC 2019 (96.8% and 95.3%). Kumamaru and CAPE scores had low sensitivity. All scores had low positive and high negative predictive values. CONCLUSION: For prognosis of 7- and 30-day mortality in APE, PEMS score has the highest specificity. ESC 2019 shows the highest sensitivity. All scores had low positive and high negative predictive values.

Low skeletal muscle mass predicts treatment response in oncology: a meta-analysis.

OBJECTIVES: Low skeletal muscle mass (LSMM) predicts relevant clinical outcomes in oncologic patients. The purpose of this study was to perform a meta-analysis of data regarding associations between LSMM and treatment response (TR) in oncology. METHODS: MEDLINE, Cochrane, and SCOPUS databases were screened for relationships between LSMM and TR in oncologic patients up to November 2022. Overall, 35 studies met the inclusion criteria. The meta-analysis was performed using RevMan 5.4 software. RESULTS: The collected 35 studies comprised 3858 patients. In 1682 patients (43.6%), LSMM was diagnosed. In the overall sample, LSMM predicted a negatively objective response rate (ORR), OR = 0.70, 95% CI = (0.54-0.91), p = 0.007, and disease control rate (DCR), OR = 0.69, 95% CI = (0.50-0.95), p = 0.02. In the curative setting, LSMM predicted a negatively ORR, OR = 0.24, 95% CI = (0.12-0.50), p = 0.0001, but not DCR, OR = 0.60, 95% CI = (0.31-1.18), p = 0.14. In palliative treatment with conventional chemotherapies, LSMM did not predict ORR: OR = 0.94, 95% CI (0.57-1.55), p = 0.81, and DCR: OR = 1.13, 95% CI (0.38-3.40), p = 0.82. In palliative treatment with tyrosine kinase inhibitors (TKI), LSMM did not predict TR: ORR, OR = 0.74, 95% CI (0.44-1.26), p = 0.27, and DCR, OR = 1.04, 95% CI (0.53-2.05), p = 0.90. In palliative immunotherapy, LSMM tended to predict ORR, OR = 0.74, 95% CI = (0.54-1.01), p = 0.06, and predicted DCR, OR = 0.53, 95% CI = (0.37-0.76), p = 0.0006. CONCLUSION: LSMM is a risk factor for poor TR in curative chemotherapy in the adjuvant and/or neoadjuvant setting. LSMM is a risk factor for treatment failure in treatment with immunotherapy. Finally, LSMM does not influence TR in palliative treatment with conventional chemotherapy and/or TKIs. KEY POINTS: • Low skeletal muscle mass (LSMM) predicts treatment response (TR) to chemotherapy in the adjuvant and/or neoadjuvant setting. • LSMM predicts TR in immunotherapy. • LSMM does not influence TR in palliative chemotherapy.

Apparent diffusion coefficient correlates with different histopathological features in several intrahepatic tumors.

OBJECTIVES: To investigate associations between apparent diffusion coefficient (ADC) and cell count, Ki 67, tumor-stroma ratio (TSR), and tumoral lymphocytes in different hepatic malignancies. METHODS: We identified 149 cases with performed liver biopsies: hepatocellular cancer (HCC, n = 53), intrahepatic cholangiocarcinoma (iCC, n = 29), metastases of colorectal cancer (CRC, n = 24), metastases of breast cancer (BC, n = 28), and metastases of pancreatic cancer (PC, n = 15). MRI was performed on a 1.5-T scanner with an axial echo-planar sequence. MRI was done before biopsy. Biopsy images of target lesions were selected. The cylindrical region of interest was placed on the ADC map of target lesions in accordance with the needle position on the biopsy images. Mean ADC values were estimated. TSR, cell counts, proliferation index Ki 67, and number of tumor-infiltrating lymphocytes were estimated. Spearman's rank correlation coefficients and intraclass correlation coefficients were calculated. RESULTS: Inter-reader agreement was excellent regarding the ADC measurements. In HCC, ADC correlated with cell count (r = - 0.68, p < 0.001) and with TSR (r = 0.31, p = 0.024). In iCC, ADC correlated with TSR (r = 0.60, p < 0.001) and with cell count (r = - 0.54, p = 0.002). In CRC metastases, ADC correlated with cell count (r = - 0.54 p = 0.006) and with Ki 67 (r = - 0.46, p = 0.024). In BC liver metastases, ADC correlated with TSR (r = 0.55, p < 0.002) and with Ki 67 (r = - 0.51, p = 0.006). In PC metastases, no significant correlations were found. CONCLUSIONS: ADC correlated with tumor cellularity in HCC, iCC, and CRC liver metastases. ADC reflects TSR in BC liver metastases, HCC, and iCC. ADC cannot reflect intratumoral lymphocytes. CLINICAL RELEVANCE STATEMENT: The present study shows that the apparent diffusion coefficient can be used as a surrogate imaging marker for different histopathological features in several malignant hepatic lesions. KEY POINTS: • ADC reflects different histopathological features in several hepatic tumors. • ADC correlates with tumor cellularity in HCC, iCC, and CRC metastases. • ADC strongly correlates with tumor-stroma ratio in BC metastases and iCC.

Apparent diffusion coefficient for assessing Crohn's disease activity: a meta-analysis.

PURPOSE: To analyze relationships betweenapparent diffusion coefficient (ADC) and activity parameters of Crohn's disease, e.g., length and wall thickness, CRP, FCP, MaRIA, CDAI, SES-CD, histologic inflammatory activity score, and the histological fibrotic score, based upon published data. MATERIALS AND METHODS: MEDLINE library, Scopus, and Embase databases were screened for association between ADC and activity parameters of Crohn's disease in patients with Crohn's disease up to Mai 2021. Overall, 21 studies with 1053 patients were identified. The following data were extracted from the literature: number of patients, correlation coefficients between ADC and length as well as wall thickness, CRP, FCP, MaRIA, CDAI, and SES-CD, inflammatory activity score, and fibrotic score. Associations between ADC and activity parameters were analyzed by Spearman's correlation coefficient. The studies' methodologic quality was evaluated by using the Quality Assessment of Diagnostic Studies (QUADAS 2) instrument, revealing a low risk of bias. RESULTS: In the overall sample, the pooled correlation coefficient between ADC and CDAI was -0.8 (95% CI = [-0.94; -0.65]), between ADC and MaRIA -0.66 (95% CI = [-0.79; -0.53]). A strong association was observed between ADC and SES-CD with a pooled correlation of -0.66 (95% CI = [-0.87; -0.46]). The pooled sensitivity to discriminate between involved and non-involved bowel segments was 0.89, with an area under the curve of 0.89 CONCLUSIONS: ADC showed strong inverse correlations with CDAI, MaRIA, and SES-CD scores. However, the role of ADC in assessing fibrotic changes in the bowel wall is limited. ADC can reflect acute inflammatory reactions but not systemic inflammation. KEY POINTS: • ADC value can reflect acute inflammatory reactions but not systemic inflammation. • ADC is inversely correlated with CDAI, MaRIA, and SES-CD. • The role of ADC in assessing fibrotic changes in the bowel wall is limited.

Computed Tomography-Defined Fat Composition as a Prognostic Marker in Gastric Adenocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Computed tomography (CT)-defined fat quantification has been an emergent field of research in oncology. It was shown that this parameter is predictive and prognostic of several clinically relevant factors in several tumor entities. OBJECTIVE: Our aim was to establish the effect of visceral (VFA) and subcutaneous fat areas (SFA) on overall survival (OS), disease-free survival (DFS), and postoperative complications in gastric cancer patients based on a large patient sample. METHODS: MEDLINE library, EMBASE, and SCOPUS databases were screened for the associations between VFA and SFA defined by CT images and OS, DFS, and postoperative complications in gastric cancer patients up to August 2022. The primary endpoint of the systematic review was the hazard ratio for the outcome parameters. High VFA was, in most studies, defined by the threshold value of 100 cm2. In total, 9 studies were suitable for the analysis and included in the present study. RESULTS: The included studies comprised 3,713 patients. The identified frequency of visceral obesity was 44.9%. The pooled hazard ratio for the effect of high VFA on OS was 1.28 (95% CI 1.09-1.49, p = 0.002). For SFA, it was 1.87 (95% CI 1.45-2.42, p < 0.0001). The pooled hazard ratio for the influence of high VFA on DFS was 1.17 (95% CI 0.95-1.43, p = 0.14). The pooled odds ratio for the associations between VFA and postoperative complications was 1.36 (95% CI 1.09-1.69, p = 0.006). CONCLUSION: CT-defined VFA and SFA influence OS in patients with gastric cancer. VFA also influences the occurrence of postoperative complications. Therefore, assessment of fat areas should be included in clinical routine in patients with gastric cancer.

How hazardous are hazard ratios? An empirical investigation of individual patient data from 27 large randomized clinical trials.

The use of hazard ratios as the standard treatment effect estimators for randomized trials with time-to-event outcomes has been the subject of repeated criticisms in recent years, e.g., for its non-collapsibility or with respect to (causal) interpretation. Another important issue is the built-in selection bias, which arises when the treatment is effective and when there are unobserved or not included prognostic factors that influence time-to-event. In these cases, the hazard ratio has even been termed "hazardous" because it is estimated from groups that increasingly differ in their (unobserved or omitted) baseline characteristics, yielding biased treatment estimates. We therefore adapt the Landmarking approach to assess the effect of ignoring a gradually increasing proportion of early events on the estimated hazard ratio. We propose an extension called "Dynamic Landmarking". This approach is based on successive deletion of observations, refitting Cox models and balance checking of omitted but observed prognostic factors, to obtain a visualization that can indicate built-in selection bias. In a small proof-of-concept simulation, we show that our approach is valid under the given assumptions. We further use "Dynamic Landmarking" to assess the suspected selection bias in the individual patient data sets of 27 large randomized clinical trials (RCTs). Surprisingly, we find no empirical evidence of selection bias in these RCTs and thus conclude that the supposed bias of the hazard ratio is of little practical relevance in most cases. This is mainly due to treatment effects in RCTs being small and the patient populations being homogeneous, e.g., due to inclusion and exclusion criteria.

Ultrafast switching with nonlinear optics in thin films.

We demonstrate a novel, to the best of our knowledge, concept for an all-optical switch based on the optical Kerr effect in optical interference coatings. The utilization of the internal intensity enhancement in thin film coatings as well as the integration of highly nonlinear materials enable a novel approach for self-induced optical switching. The paper gives insight into the design of the layer stack, suitable materials, and the characterization of the switching behavior of the manufactured components. A modulation depth of 30% could be achieved, which prepares the way for later applications in mode locking.

Reduction of nanoparticles in optical thin films through ion etching.

Contaminating particles in optical thin films can lead to the formation of nodules and reduction of laser induced damage threshold (LIDT). This work investigates the suitability of ion etching of the substrates to reduce the impact of nanoparticles. Initial investigations suggest that ion etching can remove nanoparticles from the sample surface; however, doing so introduces texturing to the surface of the substrate. This texturing leads to an increase in optical scattering loss, though LIDT measurements show no significant reduction in the durability of the substrate.

Substrate-free miniaturized thin-film filters for single-element coarse wavelength division multiplexing fibers.

We have created high-precision, miniaturized, substrate-free filters, based on ion beam sputtering on a sacrificial substrate. The sacrificial layer is cost efficient and environmentally friendly and can be dissolved using only water. We demonstrate an improved performance compared to filters on thin polymer layers from the same coating run. With these filters, a single-element coarse wavelength division multiplexing transmitting device for telecommunication applications can be realized by inserting the filter between fiber ends.

Enabling rotary atomic layer deposition for optical applications.

Atomic layer deposition (ALD) has been proven as an excellent method for depositing high-quality optical coatings due to its outstanding film quality and precise process control. Unfortunately, batch ALD requires time-consuming purge steps, which leads to low deposition rates and highly time-intensive processes for complex multilayer coatings. Recently, rotary ALD has been proposed for optical applications. In this, to the best of our knowledge, novel concept, each process step takes place in a separate part of the reactor divided by pressure and nitrogen curtains. To be coated, substrates are rotated through these zones. During each rotation, an ALD cycle is completed, and the deposition rate depends primarily on the rotation speed. In this work, the performance of a novel rotary ALD coating tool for optical applications is investigated and characterized with S i O 2 and T a 2 O 5 layers. Low absorption levels of <3.1p p m and <6.0p p m are demonstrated at 1064 nm for around 186.2 nm thick single layers of T a 2 O 5 and 1032 nm S i O 2, respectively. Growth rates up to 0.18 nm/s on fused silica substrates were achieved. Furthermore, excellent non-uniformity is also demonstrated, with values reaching as low as ±0.53% and ±1.07% over an area of 135×60m m for T a 2 O 5 and S i O 2, respectively.

Increasing social disparities in obesity among 15 000 pre-schoolers in a German district from 2009 to 2019.

BACKGROUND: Although childhood obesity prevalence has stagnated in many high-income regions after decades of increase, it continues to be a major public health problem with adverse effects. The objective was to examine obesity trends as a function of parental social status to identify obesity disparities among children. METHODS: Data from school entry examinations from 2009 to 2019 of 14 952 pre-schoolers in one German district were used. Logistic regression models (obesity/overweight as dependent variable) and a linear regression [BMI z-score (BMIz) as dependent variable] were performed adjusted for social status and sex to investigate time trends in overweight and obesity. RESULTS: Overall, we found an increase of obesity over time [odds ratio (ORs): 1.03 per year, 95% CI: 1.01-1.06]. Children with low social status had an OR of 1.08 per year (95% CI: 1.03-1.13), while the trend was less expressed in children with high social status (OR: 1.03 per year, 95% CI: 0.98-1.08). The mean BMIz decreased per year (regression coefficient -0.005 per year, 95% CI: -0.01 to 0.0) when considering all children. This decrease was more pronounced in children with high social status (regression coefficient: -0.011 per year, 95% CI: -0.019 to -0.004), compared with a slight increase of 0.014 (95% CI: -0.003 to 0.03) per year among children with low social status. Also, children with low parental social status were heavier and smaller than their peers with high social status. CONCLUSIONS: Although the mean BMIz decreased among pre-schoolers, obesity prevalence and status-related inequity in obesity prevalence increased from 2009 to 2019 in the region studied.

Epicardial adipose tissue as a prognostic marker in acute pulmonary embolism.

BACKGROUND: Epicardial adipose tissue (EAT) has been established as a quantitative imaging biomarker associated with disease severity in coronary heart disease. Our aim was to use this prognostic marker derived from computed tomography pulmonary angiography (CTPA) for the prediction of mortality and prognosis in patients with acute pulmonary embolism. METHODS: The clinical database was retrospectively screened for patients with acute pulmonary embolism between 2015 and 2021. Overall, 513 patients (216 female, 42.1%) were included in the analysis. The study end-point was 30-day mortality. Epicardial adipose tissue was measured on the diagnostic CTPA in a semiquantitative manner. The volume and density of EAT were measured for every patient. RESULTS: Overall, 60 patients (10.4%) died within the 30-day observation period. The mean EAT volume was 128.3 ± 65.0 cm3 in survivors and 154.6 ± 84.5 cm3 in nonsurvivors (p = 0.02). The density of EAT was -79.4 ± 8.3 HU in survivors and -76.0 ± 8.4 HU in nonsurvivors (p = 0.86), and EAT density was associated with 30-day mortality (odds ratio [OR] = 1.07; 95% confidence interval [CI]: 1.03; 1.1, p < 0.001) but did not remain statistically significant in multivariable analysis. No association was identified between EAT volume and 30-day mortality (OR = 1.0; 95% CI: 1.0; 1.0, p = 0.48). CONCLUSION: There might be an association between EAT density and mortality in patients with acute pulmonary embolism. Further studies are needed to elucidate the prognostic relevance of EAT parameters in patients with acute pulmonary embolism.

Low Skeletal Muscle Mass Predicts Relevant Outcomes in Palliative Urological Oncology: A Systematic Review and Meta-Analysis.

INTRODUCTION: Low skeletal muscle mass (LSMM) can be assessed by cross-sectional imaging. LSMM is associated with several clinically relevant factors in various disorders with predictive and prognostic implications. METHODS: Our aim was to establish the effect of computed tomography (CT)-defined LSMM on mortality in renal cell cancer (RCC) and urothelial carcinoma (UC) undergoing palliative treatment. The MEDLINE library, Cochrane, and SCOPUS databases were screened for the associations between CT-defined LSMM up to May 2022. In total, 11 studies were suitable for the analysis. RESULTS: The included studies comprised 481 patients with RCC and 394 patients with UC. The pooled hazard ratio for the association between LSMM and overall survival was 1.64 (95% CI: 0.90-2.99), p = 0.10 in univariable analysis and 1.55 (95% CI: 0.91-2.63), p = 0.10 in multivariable analysis for RCC. For UC, the pooled hazard ratio was 2.75 (95% CI: 1.77-4.28), p < 0.00001 in univariable, and 2.77 (95% CI: 1.91-4.02), p < 0.00001 in multivariable analysis. For progression-free survival, it was 2.02 (95% CI: 1.24-3.27), p = 0.004 for RCC and 2.43 (95% CI: 1.59-3.74), p < 0.0001 for UC (univariable analysis). CONCLUSIONS: CT-defined LSMM predicts OS and PFS in RCC and UC in the palliative setting. The effect was higher in UC. Therefore, LSMM assessment should be included as a relevant prognostic biomarker in clinical routine.

Genetic amniocentesis using atraumatic 29 gauge needle in patients having a chorioamniotic separation.

OBJECTIVES: Chorioamniotic separation (CAS) at the time of standard amniocentesis (AC) is a risk factor for postprocedural complications and should be avoided. The aim of this study was to quantify procedure-related risks after AC with a 29G-needle in cases of CAS, and evaluation of perinatal outcome in CAS after 15 weeks' gestation (GW). METHODS: Retrospective analysis of genetic AC with a pencil-point 29G needle after 15 completed GW in pregnancies, in which the fetal membranes were not yet fused. Included into the study were women aged 16-44 years with at least 15 completed GWs referred for second trimester AC to identify fetal chromosomal aberrations. RESULTS: 437 ACs were made in total with the 29G-needle. The median maternal age was 30 (16-44) years. 145 cases showed CAS where the distance between chorion and amnion was 0.10-10.02 mm at AC. 38 pregnancies were terminated, 37 of which had a genetic disorder. The risk of aneuploidy increases by a factor of 2 (95% CI 1.4-2.8) for every 1 mm of CAS enlargement. No procedure-related complications were found up to two weeks after the AC. CONCLUSIONS: CAS seems to be massively underreported. Early diagnosis in case of CAS is something to strive for as CAS could be an indicator of genetic abnormalities - a "soft marker". With the atraumatic 29G needle, the risk of complications after AC in CAS seems to be very low.

Breast Nurse Intervention to Improve Adherence to Endocrine Therapy Among Breast Cancer Patients in South Ethiopia.

INTRODUCTION: Many women in rural Ethiopia do not receive adjuvant therapy following breast cancer surgery despite the majority being diagnosed with estrogen-receptor-positive breast cancer and tamoxifen being available in the country. We aimed to compare a breast nurse intervention to improve adherence to tamoxifen therapy for breast cancer patients. METHODS AND MATERIALS: The 8 hospitals were randomized to intervention and control sites. Between February 2018 and December 2019, patients with breast cancer were recruited after their initial surgery. The primary outcome of the study was adherence to tamoxifen therapy by evaluating 12-month medication-refill data with medication possession ratio (MPR) and using a simplified medication adherence scale (SMAQ) in a subjective assessment. RESULTS: A total of 162 patients were recruited (87 intervention and 75 control). Trained nurses delivered education and provided literacy material, gave additional empathetic counselling, phone call reminders, and monitoring of medication refill at the intervention hospitals. Adherence according to MPR at 12 months was high in both the intervention (90%) and control sites (79.3%) (P = .302). The SMAQ revealed that adherence at intervention sites was 70% compared with 44.8% in the control sites (P = .036) at 12 months. Persistence to therapy was found to be 91.2% in the intervention and 77.8% in the control sites during the one-year period (P = .010). CONCLUSION: Breast nurses can improve cost-effective endocrine therapy adherence at peripheral hospitals in low-resource settings. We recommend such task sharing to overcome the shortage of oncologists and distances to central cancer centers.

Generation of 15 nJ pulse energy by a sub-150 fs thulium-doped fiber Mamyshev oscillator.

Mamyshev oscillators have pushed the frontiers in output parameters of ytterbium- and erbium-based ultrafast fiber oscillators in the spectral region around 1 µm and 1.5 µm within the last few years tremendously. In order to expand the superior performance toward the 2 µm spectral region, we present in this Letter an experimental investigation of the generation of high-energy pulses by a thulium-doped fiber Mamyshev oscillator. Generating highly energetic pulses is enabled by a tailored redshifted gain spectrum in a highly doped double-clad fiber. The oscillator emits pulses with an energy of up to 15 nJ, which can be compressed to 140 fs.