Waldkrankenhaus Protestant Hospital

OBJECTIVES: The early discharge of neonates from hospitals makes transcutaneous measurement of total bilirubin concentration a useful tool to monitor neonatal jaundice. The objectives of this study were to determine whether 1) transcutaneous bilirubin (TcB) measurement, as performed using BiliCheck (BC), correlates with total serum bilirubin (TSB) levels, measured with standard laboratory methods and with high-pressure liquid chromatography (HPLC-B); 2) infant race, gestational age, postnatal age, or body weight interferes with the measurement of TcB levels in newborn infants; 3) the variability of the TcB measurement is comparable to the variability of TSB measurements; and 4) TcB measurements obtained from the forehead (BCF) and sternum (BCS) generate comparable results. STUDY DESIGN: Newborn infants who were <28 days and >30 weeks' gestational age and who underwent tests for TSB as part of their normal care in 6 different European hospitals were studied. A total of 210 infants were enrolled in the study, 35 at each site. Near simultaneous (within +/- 30 minutes) blood collection for TSB and BCF and BCS measurements were performed. TSB levels were determined by the serum bilirubin method in use at each site, and all HPLC-B determinations were made at the same, independent laboratory. RESULTS: The study group consisted of 140 white, 31 Asian, 14 Hispanic, 9 African, and another 16 newborns of different races. The correlation coefficient (r) between BCF and HPLC-B was 0.890 (95% confidence interval = 0.858-0.915). BCF and BCS generated similar results (r value = 0.890 for BCF and 0.881 for BCS), even if BCS slightly overestimated (mean error = -0.04 mg/dL) and BCF slightly underestimated (mean error = 0.96 mg/dL) in comparison with HPLC-B. Analysis of covariance demonstrated that BC accuracy was independent of race, birth weight, gestational age, and postnatal age of the newborn. Receiver operating characteristic curves were evaluated for BCF and TSB, each compared with HPLC-B. With the use of a cutoff point for HPLC-B of 13 mg/dL (222 micromol/L) and a cutoff of 11 mg/dL on the BCF and TSB, similar sensitivity/specificity (93%/73% for BCF, 95%/76% for TSB) were observed. The use of a cutoff point for HPLC-B of 17 mg/dL (290 micromol/L) and 14 mg/dL (240 micromol/L) for BCF and TSB also produced similar sensitivity/specificity (90%/87% for the BC and 87%/83% for TSB). CONCLUSIONS: Because the correlation coefficient for HPLC-B and BCF is very similar to that found for HPLC-B and laboratory TSB, BC could be used not only as a screening device but also as a reliable substitute of TSB determination. At higher levels of TSB, in which phototherapy and/or exchange transfusion might be considered, BC performed slightly better than the laboratory. The accuracy and precision of the TcB measurement in this study was observed to be comparable to the standard of care laboratory test.

PURPOSE: The aim of this meta-analysis was to evaluate the clinical outcomes and risks of anterior cruciate ligament (ACL) surgery in children and adolescents. METHODS: We electronically searched Medline, the Cochrane Controlled Trial Database, Embase, and Medpilot for studies on surgical treatment for ACL ruptures in skeletally immature patients. We extracted baseline demographics, follow-up intervals, surgical details (i.e., ligament suture or reconstruction, physeal-sparing or transphyseal techniques, type of transplant, and methods of fixation). Endpoints comprised rates of growth disturbances and reruptures, as well as knee function (measured by the International Knee Documentation Committee's documentation system and the Lysholm score). Unweighted overall effect sizes (risks, risk ratios [RRs], and means of functional scores) were estimated by use of crude nominators and denominators, and random-effects meta-regression analysis was used for weighted data synthesis. RESULTS: A total of 55 articles reporting on 935 patients (median age, 13 years; range, 1.5 to 16 years) were suitable for the study. After a median follow-up of 40 months (range, 14 to 89 months), the weighted rate of leg-length differences or axis deviations was 1.8% (95% confidence interval [CI], 0% to 3.9%] and that of reruptures was 4.8% (95% CI, 2.9% to 6.7%). Excellent or good function (International Knee Documentation Committee grade A or B) was achieved in 84.2% (95% CI, 75.8% to 92.6%) of all knees, and Lysholm scores averaged 96.3 (95% CI, 95.5 to 97.2). Transphyseal reconstruction was associated with a significantly lower risk of leg-length differences or axis deviations compared with physeal-sparing techniques (1.9% v 5.8%; RR, 0.34; 95% CI, 0.14 to 0.81) but had a higher risk of rerupture (4.2% v 1.4%; RR, 2.91; 95% CI, 0.70 to 12.12). Sutures did not result in any growth disturbances, with a weighted rerupture rate of 4.6% (95% CI, 2.6 to 6.7). Fixation far from the joint line fared better than close fixation with regard to this endpoint (1.4% v 3.2%; RR, 0.42; 95% CI, 0.09 to 1.93). Bone-patellar tendon-bone grafts, which are also less likely to fail, were associated with higher risks of leg-length differences or axis deviations than were hamstrings (3.6% v 2.0%; RR, 1.82; 95% CI, 0.66 to 5.03). Meta-regression did not show a significant impact of the publication year on event rates. CONCLUSIONS: This meta-analysis showed low rates of leg-length differences or axis deviations and graft failures after ACL reconstruction in skeletally immature patients. Hamstring transplants may lower the risk of leg-length differences or axis deviations, and physeal-sparing techniques may increase the risk. Randomized controlled trials are needed to clarify important issues in managing ACL ruptures in children and adolescents. LEVEL OF EVIDENCE: Level IV, meta-analysis of case series.

BACKGROUND: Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear. METHODS: In this prospective, randomized, noninferiority trial, we investigated the omission of axillary surgery as compared with sentinel-lymph-node biopsy in patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size, ≤5 cm) who were scheduled to undergo breast-conserving surgery. We report here the per-protocol analysis of invasive disease-free survival (the primary efficacy outcome). To show the noninferiority of the omission of axillary surgery, the 5-year invasive disease-free survival rate had to be at least 85%, and the upper limit of the confidence interval for the hazard ratio for invasive disease or death had to be below 1.271. RESULTS: A total of 5502 eligible patients (90% with clinical T1 cancer and 79% with pathological T1 cancer) underwent randomization in a 1:4 ratio. The per-protocol population included 4858 patients; 962 were assigned to undergo treatment without axillary surgery (the surgery-omission group), and 3896 to undergo sentinel-lymph-node biopsy (the surgery group). The median follow-up was 73.6 months. The estimated 5-year invasive disease-free survival rate was 91.9% (95% confidence interval [CI], 89.9 to 93.5) among patients in the surgery-omission group and 91.7% (95% CI, 90.8 to 92.6) among patients in the surgery group, with a hazard ratio of 0.91 (95% CI, 0.73 to 1.14), which was below the prespecified noninferiority margin. The analysis of the first primary-outcome events (occurrence or recurrence of invasive disease or death from any cause), which occurred in a total of 525 patients (10.8%), showed apparent differences between the surgery-omission group and the surgery group in the incidence of axillary recurrence (1.0% vs. 0.3%) and death (1.4% vs. 2.4%). The safety analysis indicates that patients in the surgery-omission group had a lower incidence of lymphedema, greater arm mobility, and less pain with movement of the arm or shoulder than patients who underwent sentinel-lymph-node biopsy. CONCLUSIONS: In this trial involving patients with clinically node-negative, T1 or T2 invasive breast cancer (90% with clinical T1 cancer and 79% with pathological T1 cancer), omission of surgical axillary staging was noninferior to sentinel-lymph-node biopsy after a median follow-up of 6 years. (Funded by the German Cancer Aid; INSEMA ClinicalTrials.gov number, NCT02466737.).

OBJECTIVE: This study aimed to investigate the feasibility and accuracy of non-radioactive TLN biopsy and TAD in routine clinical practice. BACKGROUND DATA: TAD involves TLN biopsy (TLNB) and sentinel lymph node biopsy and was recently introduced as a new standard for less invasive axillary staging in BC patients undergoing neoadjuvant systemic therapy (NST); however, clinical evidence is limited. METHODS: The SenTa study is a prospective registry study conducted at 50 centers. Patients with invasive BC who nderwent clip insertion into the most suspicious axillary lymph node were eligible. Axillary surgery was performed with or without sentinel lymph node biopsy, TLNB, and/or axillary lymph node dissection (ALND). Main endpoints were the detection rate and FNR of TLNB and TAD after NST. RESULTS: Between 2017 and 2018, 548 consecutive BC patients underwent clip placement into biopsy-confirmed positive lymph nodes. After NST (n = 473), the clipped TLN was intraoperatively resected in 329 of 423 patients [77.8%, 95% confidence interval (CI): 74.0-82.0]. TAD was successful in 199 of 229 patients (detection rate: 86.9%, 95% CI: 81.8-91.0), the SLN and TLN were identical in 129 patient (64.8%). FNRs were 7.2% (8 of 111, 95% CI: 3.1-13.6) for TLNB followed by ALND (n = 203) and 4.3% (2 of 46, 95% CI: 0.5-14.8) for TAD followed by ALND (n = 77). CONCLUSIONS: The SenTa study demonstrates the feasibility of TAD in a real-world cohort of BC patients. Our findings are of great importance for de-escalation of surgical strategies.

Iatrogenic, isolated weakness or paralysis of the extensor hallucis longus muscle is a common complication in patients who have had a proximal tibial and fibular osteotomy. To investigate why this complication occurs, we dissected the deep peroneal nerve and neighboring structures, such as the tibia and fibula and the muscles of the leg, in twenty-nine specimens from cadavera, paying special attention to the motor branches supplying the extensor hallucis longus. Of forty-six motor nerves that were identified, eight entered the muscle from the lateral side in an area seventy to 150 millimeters distal to the fibular head; all of them ran close to the fibular periosteum. We suggest that, in some patients, the nerve supply to the extensor hallucis longus is at high risk for injury during a tibial osteotomy because of the proximity of the bone to the motor branches.

BACKGROUND: For premature neonates needing parenteral nutrition (PN), a balanced lipid supply is crucial. The authors hypothesized that a lipid emulsion containing medium-chain triglycerides (MCTs) and soybean, olive, and fish oils would be as safe and well tolerated as a soybean emulsion while beneficially influencing the fatty acid profile. METHODS: Double-blind, controlled study in 53 neonates (<34 weeks' gestation) randomized to receive at least 7 days of PN containing either an emulsion of MCTs and soybean, olive, and fish oils or a soybean oil emulsion. Target lipid dosage was 1.0 g fat/kg body weight [BW]/d on days 1-3, 2 g/kg BW/d on day 4, 3 g/kg BW/d on day 5, and 3.5 g/kg BW/d on days 6-14. RESULTS: Test emulsion vs control, mean ± SD: baseline triglyceride concentrations were 0.52 ± 0.16 vs 0.54 ± 0.19 mmol/L and increased similarly in both groups to 0.69 ± 0.38 vs 0.67 ± 0.36 on day 8 of treatment (P = .781 for change). A significantly higher decrease in total and direct bilirubin vs baseline was seen in the test group compared with the control group P < .05 between groups). In plasma and red blood cell phospholipids, eicosapentaenoic acid and docosahexaenoic acid were higher, and the n-6/n-3 fatty acid ratio was lower in the test group (P < .05 vs control). CONCLUSIONS: The lipid emulsion, based on a mixture of MCTs and soybean, olive, and fish oils, was safe and well tolerated by preterm infants while beneficially modulating the fatty acid profile.

Background: Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). The optimal chemotherapy regimen is unclear. Weekly nab-paclitaxel vs conventional paclitaxel or addition of carboplatin to anthracycline-taxane results in higher pCR rates with uncertain survival impact. We evaluated carboplatin vs gemcitabine with a nab-paclitaxel backbone as a short 12-week A-free regimen with a focus on early response. Methods: Patients with TNBC (estrogen receptor/progesterone receptor < 1%, human epidermal growth factor receptor 2-negative, cT1c-cT4c, cN0/+) were randomly assigned to A: nab-paclitaxel 125 mg/m2/gemcitabine 1000 mg/m2 d1,8 three times weekly (q3w); vs B: nab-paclitaxel 125 mg/m2/carboplatin AUC2 day 1,8 q3w. The trial was powered for a pCR (ypT0/is ypN0) comparison by therapy arm and early response (defined as Ki-67 decrease >30% or < 500 invasive tumor cells in the three-week serial biopsy). All statistical tests were two-sided. Results: A total of 336 patients were enrolled (48 centers, arms A/B: n = 182/154). The median age was 50 years. At baseline (A vs B), 62.6% and 62.9% had cT2-4c tumors; 86.8% and 90.9% completed therapy per protocol, respectively. pCR favored arm B (28.7%, 95% CI = 0.22 to 0.36, vs 45.9%, 95% CI = 0.38 to 0.54; 95% CI(dBA) = 6.2% to 27.9%, P = .002) and was lower in nonresponders than in early responders (19.5% vs 44.4%, P < .001) or in patients with unclassifiable early response (50.0%). The nab-paclitaxel/gemcitabine was associated with more frequent dose reductions (20.6% vs 11.9%, P = .04), treatment-related serious adverse events (11.1% vs 5.3%, P = .07), grade 3-4 infections (7.2% vs 2.6%, P = .07), and grade 3-4 ALAT elevations (11.7 vs 3.3%, P = .01). Conclusions: This first large randomized trial suggests high efficacy and excellent tolerability of a neoadjuvant nab-paclitaxel/carboplatin regimen, superior to nab-paclitaxel/gemcitabine in TNBC. De-escalation of further chemotherapy in patients with early pCR after a short anthracycline-free regimen is a promising field of future research. Early necrotic morphological changes and/or proliferation decrease after the first therapy cycle seem to be associated with subsequent pCR.

PURPOSE To our knowledge, WSG-ADAPT-HR+/HER2– (ClinicalTrials.gov identifier: NCT01779206 ; n = 5,625 registered) is the first trial combining the 21-gene expression assay (recurrence score [RS]) and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer. MATERIALS AND METHODS Baseline and postendocrine Ki67 (Ki67 post ) were evaluated centrally. In the endocrine trial, all patients received exclusively ET: patients with pathologic regional lymph node status (pN) 0-1 (ie, 0-3 involved lymph nodes) entered control arm if RS ≤ 11 and experimental arm if RS12-25 with ET response (Ki67 post ≤ 10%). All other patients (including N0-1 RS12-25 without ET response) received dose-dense chemotherapy (CT) followed by ET in the CT trial. Primary end point of the endocrine trial was noninferiority of 5-year invasive disease-free survival (5y-iDFS) in experimental ( v control) arm; secondary end points included distant DFS, overall survival, and translational research. RESULTS Intention-to-treat population comprised 2,290 patients (n = 1,422 experimental v n = 868 control): 26.3% versus 34.6% premenopausal and 27.4% versus 24.0% pN1. One-sided 95% lower confidence limit of the 5y-iDFS difference was –3.3%, establishing prespecified noninferiority ( P = .05). 5y-iDFS was 92.6% (95% CI, 90.8 to 94.0) in experimental versus 93.9% (95% CI, 91.8 to 95.4) in control arm; 5-year distant DFS was 95.6% versus 96.3%, and 5-year overall survival 97.3% versus 98.0%, respectively. Differences were similar in age and nodal subgroups. In N0-1 RS12-25, outcome of ET responders (ET alone) was comparable with that of ET nonresponders (CT) for age &gt; 50 years and superior for age ≤ 50 years. ET response was more likely with aromatase inhibitors (mostly postmenopausal) than with tamoxifen (mostly premenopausal): 78.1% versus 41.1% ( P &lt; .001). ET response was 78.8% in RS0-11, 62.2% in RS12-25, and 32.7% in RS &gt; 25 (n = 4,203, P &lt; .001). CONCLUSION WSG-ADAPT-HR+/HER2– demonstrates that guiding systemic treatment by both RS and ET response is feasible in clinical routine and spares CT in pre- and postmenopausal patients with ≤ 3 involved lymph nodes.

We describe the development and application of a modified version of the radiologic scoring method proposed by Larsen in patients with rheumatoid arthritis (RA). We modified Larsen's method adding a semiquantitative description of the loss of joint surface area and provide standardized reference films for all stages at different anatomical sites (metacarpophalangeal joints, proximal interphalangeal joints, wrists, metatarsophalangeal joints). To evaluate the method, standard anteroposterior radiographs of hands, wrists and forefeet of 24 patients with early erosive RA taken at baseline (t0) and after 36 months (t1) were read by 2 raters in a blinded fashion. The interrater difference was compared with the interpatient (t0 to t1) difference using a hierarchical analysis of variance. Moreover, the method was applied to patients included in a 2 year clinical trial to evaluate the efficacy of intramuscular methotrexate (MTX) and gold sodium thiomalate (GSTM) with radiographs taken at baseline and after 6, 12, and 24 months. There was a good agreement between the 2 raters and the change could be well documented. The estimation of the intrapatient variance (at t0 and t1) was 8 times higher than the estimation of the interreader variance. The method was easily applicable in 57 patients treated with MTX and 53 patients under treatment with GSTM, showing a slowing of radiologic progression after Month 6 with both drugs. The modification of Larsen's scoring method is a reliable measure to assess baseline status and radiologic progression in patients with RA.

OBJECTIVE: Outcome prediction after cardiac arrest is important to decide on continuation or withdrawal of intensive care. Neuron-specific enolase is an easily available, observer-independent prognostic biomarker. Recent studies have yielded conflicting results on its prognostic value after targeted temperature management. DESIGN, SETTING, AND PATIENTS: We analyzed neuron-specific enolase serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out-of-hospital cardiac arrest and outcome of patients from five hospitals in Germany, Austria, and Italy. Patients were treated at 33°C for 24 hours. Cerebral Performance Category was evaluated upon ICU discharge. We performed case reviews of good outcome patients with neuron-specific enolase greater than 90 μg/L and poor outcome patients with neuron-specific enolase less than or equal to 17 μg/L (upper limit of normal). MEASUREMENTS AND MAIN RESULTS: A neuron-specific enolase serum concentration greater than 90 μg/L predicted Cerebral Performance Category 4-5 with a positive predictive value of 99%, false positive rate of 0.5%, and a sensitivity of 48%. All three patients with neuron-specific enolase greater than 90 μg/L and Cerebral Performance Category 1-2 had confounders for neuron-specific enolase elevation. An neuron-specific enolase serum concentration less than or equal to 17 μg/L excluded Cerebral Performance Category 4-5 with a negative predictive value of 92%. The majority of 14 patients with neuron-specific enolase less than or equal to 17 μg/L who died had a cause of death other than hypoxic-ischemic encephalopathy. Specificity and sensitivity for prediction of poor outcome were independent of age, sex, and initial rhythm but higher for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. CONCLUSION: High neuron-specific enolase serum concentrations reliably predicted poor outcome at ICU discharge. Prediction accuracy differed and was better for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. Our "in-the-field" data indicate 90 μg/L as a threshold associated with almost no false positives at acceptable sensitivity. Confounders of neuron-specific enolase elevation should be actively considered: neuron-specific enolase-producing tumors, acute brain diseases, and hemolysis. We strongly recommend routine hemolysis quantification. Neuron-specific enolase serum concentrations less than or equal to 17 μg/L argue against hypoxic-ischemic encephalopathy incompatible with reawakening.

Human rheumatoid synovial cells in culture secrete both 72-kDa progelatinase and a complex consisting of 72-kDa progelatinase and a 24-kDa inhibitor of metalloproteinases, TIMP-2. In addition, the culture medium contains TIMP-1, the classical inhibitor of metalloproteinases, with a molecular mass of 30 kDa. TIMP-1 does not form a complex with free 72-kDa progelatinase. Free progelatinase and progelatinase complexed with TIMP-2 can be activated with the organomercury compound p-aminophenylmercury acetate. The activated complex shows less than 10% the enzyme activity of activated free gelatinase. The progelatinase-TIMP-2 complex could be shown to be an inhibitor for other metalloproteinases, such as gelatinase and collagenase secreted by human rheumatoid synovia fibroblasts, as well as for the corresponding enzymes from human neutrophils.

Background: In clinically node-negative breast cancer patients, the INSEMA trial (NCT02466737) assessed the non-inferiority of avoiding sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Here we present patient-reported outcomes (PROs) as a secondary endpoint. Methods: PROs were assessed for patients with no axillary surgery, SLNB alone, and ALND. Quality of life (QoL) questionnaire EORTC QLQ-C30 and its breast cancer module (BR23) were used at baseline (pre-surgery) and 1, 3, 6, 12, and 18 months after surgery. The QoL scores were compared using repeated measures mixed models based on the safety set. Findings: Between 2015 and 2019, 5502 patients were recruited for the first randomization, and 5154 were included in the intent-to-treat set (4124 SLNB versus 1030 no SLNB). In the case of one to three macrometastases after SLNB, 485 patients underwent second randomization (242 SLNB alone versus 243 ALND). Questionnaire completion response remained high throughout the trial: over 70% at all time points for the first randomization. There were significant differences for the BRBS (breast symptoms) and BRAS (arm symptoms) scores favoring the no SLNB group in all post-baseline assessments. Patients in the SLNB group showed significantly and clinically relevant higher scores for BRAS (differences in mean values ≥5.0 points at all times), including pain, arm swelling, and impaired mobility in all postoperative visits, with the highest difference at one month after surgery. Scoring of the QLQ-C30 questionnaire revealed no relevant differences between the treatment groups, although some comparisons were statistically significant. Interpretation: This is one of the first randomized trials investigating the omission of SLNB in clinically node-negative patients and the first to report comprehensive QoL data. Patients with no SLNB benefitted regarding arm symptoms/functioning, while no relevant differences in other scales were seen. Funding: Supported by German Cancer Aid (Deutsche Krebshilfe, Bonn, Germany), Grant No. 110580 and Grant No. 70110580 to University Medicine Rostock.

In Western countries, vegetarian diets are associated with lower intakes of energy, saturated fatty acids and animal protein and higher intakes of fibre and phytochemicals, compared to omnivorous diets. Whether the corresponding health benefits in vegetarians outweigh the risks of nutrient deficiencies has not been fully clarified. It should be noted that vegetarians often have a higher socioeconomic status, follow a more health-conscious lifestyle with higher physical activity, and refrain from smoking more often than non-vegetarians. The nutritional needs of growing children and adolescents can generally be met through a balanced, vegetable-based diet; however, due to their higher nutrient requirements per kilogramme of body weight, vegetarian children have a higher risk for developing nutrient deficiencies than adults. With a vegetarian diet, the mean intakes of some nutrients, such as the omega-3 fatty acid docosahexaenoic acid (DHA), are lower than in omnivores or those eating fish. For other nutrients, such as iron and zinc, the bioavailability from vegetable foodstuffs is reduced when the intake of phytates and fibre is high; thus, the prevalence of iron deficiency can be increased despite high vitamin C intake. In addition, vitamin B12 is only found in animal-source foods. Vitamin B12 should be supplemented in people of all age groups who follow a strict vegan diet without consuming animal products. A vegetarian diet in childhood and adolescence requires good information and supervision by a paediatrician, if necessary, in cooperation with an appropriately trained dietary specialist.

BACKGROUND: With demographic change, the number of elderly people is increasing. The aging process and associated stress diminishes their quality of life. Mindfulness-based stress reduction (MBSR) has been claimed to reduce stress and alleviate suffering. It might be a useful approach to improve the condition in the elderly. PATIENTS AND METHODS: To examine feasibility and potential effects of MBSR on nursing home residents in Germany, a non-randomized feasibility study was conducted including 22 participants; 15 of them participated in an 8-week MBSR course, 7 served as untreated comparison group. Health-related quality of life (SF-12), depressive symptoms (GDS-12R), cognitive impairment (MMST), activities of daily living (Barthel Index), satisfaction with life, physical pain and major complaints were assessed pre- and post-intervention. RESULTS: 9 out of 15 course participants completed the course (60%). They showed a significant increase in the SF-12 physical health score (p = 0.017). Depressive symptoms (GDS-12R) significantly declined within the meditation group (p = 0.04) and as compared to the untreated group (p = 0.011). In the comparison group, a significant decrease in major complaints (p = 0.011) and an increase in the SF-12 mental health score were found. The meditation group yielded positive changes in the SF-12 mental health score, in satisfaction with life and in pain intensity. CONCLUSIONS: In view of the setting, the completion rate of 60% appears to be acceptable. Significant results suggest that MBSR may help improve health-related quality of life and reduce symptoms of depression. Yet, as participants did not meet the requirement to practice independently, feasibility of conducting MBSR with elderly who live in a nursing home has to be questioned.

Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined. Most untreated individuals present with acute onset of striatal damage before age 3 (to 6) years, precipitated by infectious diseases, fever or surgery, resulting in irreversible, mostly dystonic movement disorder with limited life expectancy. In some patients, striatal damage develops insidiously. In recent years, the clinical phenotype has been extended by the finding of extrastriatal abnormalities and cognitive dysfunction, preferably in the high excreter group, as well as chronic kidney failure. Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and intensified emergency treatment during catabolic episodes, which, in combination, have substantially improved neurologic outcome. In contrast, start of treatment after onset of symptoms cannot reverse existing motor dysfunction caused by striatal damage. Dietary treatment can be relaxed after the vulnerable period for striatal damage, that is, age 6 years. However, impact of dietary relaxation on long-term outcomes is still unclear. This third revision of evidence-based recommendations aims to re-evaluate previous recommendations (Boy et al., J Inherit Metab Dis, 2017;40(1):75-101; Kolker et al., J Inherit Metab Dis 2011;34(3):677-694; Kolker et al., J Inherit Metab Dis, 2007;30(1):5-22) and to implement new research findings on the evolving phenotypic diversity as well as the impact of non-interventional variables and treatment quality on clinical outcomes.

Importance: The increasing use of neoadjuvant systemic therapy (NST) has led to substantial pathological complete response rates in patients with initially node-positive, early breast cancer, thereby questioning the need for axillary lymph node dissection (ALND). Targeted axillary dissection (TAD) is feasible for axillary staging; however, data on oncological safety are scarce. Objective: To assess 3-year clinical outcomes in patients with node-positive breast cancer who underwent TAD alone or TAD with ALND. Design, Setting, and Participants: The SenTa study is a prospective registry study and was conducted between January 2017 and October 2018. The registry includes 50 study centers in Germany. Patients with clinically node-positive breast cancer underwent clipping of the most suspicious lymph node (LN) before NST. After NST, the marked LNs and sentinel LNs were excised (TAD) followed by ALND according to the clinician's choice. Patients who did not undergo TAD were excluded. Data analysis was performed in April 2022 after 43 months of follow-up. Exposure: TAD alone vs TAD with ALND. Main Outcomes and Measures: Three-year clinical outcomes were evaluated. Results: Of 199 female patients, the median (IQR) age was 52 (45-60) years. A total of 182 patients (91.5%) had 1 to 3 suspicious LNs; 119 received TAD alone and 80 received TAD with ALND. Unadjusted invasive disease-free survival was 82.4% (95% CI, 71.5-89.4) in the TAD with ALND group and 91.2% (95% CI, 84.2-95.1) in the TAD alone group (P = .04); axillary recurrence rates were 1.4% (95% CI, 0-54.8) and 1.8% (95% CI, 0-36.4), respectively (P = .56). Adjusted multivariate Cox regression indicated that TAD alone was not associated with an increased risk of recurrence (hazard ratio [HR], 0.83; 95% CI, 0.34-2.05; P = .69) or death (HR, 1.07; 95% CI, 0.31-3.70; P = .91). Similar results were obtained for 152 patients with clinically node-negative breast cancer after NST (invasive disease-free survival: HR, 1.26; 95% CI, 0.27-5.87; P = .77; overall survival: HR, 0.81; 95% CI, 0.15-3.83; P = .74). Conclusions and Relevance: These results suggest that TAD alone in patients with mostly good clinical response to NST and at least 3 TAD LNs may confer survival outcomes and recurrence rates similar to TAD with ALND.

Melt electrospinning is a promising approach to manufacture biocompatible scaffolds for tissue engineering. In this study, melt electrospinning of poly(ε-caprolactone) onto structured, metallic collectors resulted in scaffolds with an average pore size of 250–300 μm and an average fibre diameter of 15 μm. Scaffolds were seeded with ovine osteoblasts in vitro. Cell proliferation and deposition of mineralised extracellular matrix was assessed using PicoGreen® (Thermo Fisher Scientific, Scoresby, Australia) and WAKO® HR II (WAKO, Osaka, Japan) calcium assays. Biocompatibility, cell infiltration and the growth pattern of osteoblasts on scaffolds was investigated using confocal microscopy and scanning electron microscopy. Osteoblasts proliferated on the scaffolds over an entire 40-day culture period, with excellent survival rates and deposited mineralized extracellular matrix. In general, the 3D environment of the structured melt electrospun scaffold was favourable for osteoblast cultures.

BACKGROUND: The presented prospective randomized controlled single-centre study compares the clinical outcome up to 12 months after total hip arthroplasty using a minimally invasive single-incision direct anterior (DAA) and a direct transgluteal lateral approach. METHODS: A total of 123 arthroplasties were evaluated utilizing the Harris Hip Score (HHS), the extra short musculoskeletal functional assessment questionnaire (XSFMA), the Short Form 36 (SF-36) health survey, a Stepwatch™ Activity Monitor (SAM), and a timed 25 m foot walk (T25-FW). Postoperative x-ray images after THA were reviewed to determine inclination and stem positioning. RESULTS: At final follow-up, the XSFMA functional index scores were 10.3 (anterior) and 15.08 (lateral) while the bother index summed up to a score of 15.8 (anterior) and 21.66 (lateral) respectively, thus only differing significantly for the functional index (p = 0.040 and p = 0.056). The SF-36 physical component score (PCS) was 47.49 (anterior) and 42.91 (lateral) while the mental component score (MCS) summed up to 55.0 (anterior) and 56.23 (lateral) with a significant difference evident for the PCS (p = 0.017; p = 0.714). Patients undergoing THA through a DAA undertook a mean of 6402 cycles per day while those who had undergone THA through a transgluteal approach undertook a mean of 5340 cycles per day (p = 0.012). Furthermore, the obtained outcome for the T25-FW with 18.4 s (anterior) and 19.75 s (lateral) and the maximum walking distance (5932 m and 5125 m) differed significantly (p = 0.046 and p = 0.045). The average HHS showed no significant difference equaling 92.4 points in the anterior group and 91.43 in the lateral group (p = 0.477). The radiographic analysis revealed an average cup inclination of 38.6° (anterior) and 40.28° (lateral) without signs of migration. CONCLUSION: In summary, our outcomes show that after 1 year THA through the direct anterior approach results in a higher patient activity compared to THA utilizing a transgluteal lateral approach while no differences regarding hip function are evident. TRIAL REGISTRATION: DRKS00014808 (German Clinical Trial Register DRKS); date of registration: 31.05.2018.

BACKGROUND: Although greater than 40% of breast cancers occur in patients aged ≥65 years, these individuals are frequently undertreated. Taxane-based adjuvant chemotherapy is considered the treatment of choice but to the authors' knowledge has only limited evidence in elderly patients. METHODS: Patients aged ≥65 years with a Charlson comorbidity index ≤2 and pT1/2 pN0/1 disease and either human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor-negative, grade 3 (according to Common Terminology Criteria for Adverse Events [version 3.0]), high uPA/PAI-1 or any stage pT3/4 pN2/3 breast cancer were randomized to receive 4 cycles of adjuvant epirubicin and cyclophosphamide (EC) (epirubicin at a dose of 90 mg/m(2) and cyclophosphamide at a dose of 600 mg/m(2) intravenously [iv] on day 1 every 3 22 days) or 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (cyclophosphamide at a dose of 500 mg/m(2), methotrexate at a dose of 40 mg/m(2), and 5-fluorouracil at a dose of 600 mg/m(2) iv on days 1 plus 8 every 29 days) versus 6 cycles of nab-paclitaxel and capecitabine (nPX) (nab-paclitaxel at a dose of 100 mg/m(2) iv on days 1, 8, and 15 every 21 days with 1 week of rest every 6 weeks plus capecitabine at a dose of 2000 mg/m(2) orally on days 1-14 every 21 days). Primary endpoints were treatment discontinuations and overall frequency of adverse events. RESULTS: Thirteen of 198 patients (6.6%) discontinued EC/CMF and 69 of 193 patients (35.8%) discontinued nPX (P<.001) with 1 and 5 deaths observed during treatment, respectively. Grade 3 to 5 adverse events were more frequent among patients treated with EC/CMF (90.9%) than among those treated with nPX (64.8%) (P<.001), with hematological toxicities being more frequent with EC/CMF (88.4% vs 22.3%; P<.001), but nonhematological toxicities (hand-foot syndrome, diarrhea, mucositis, fatigue, sensory neuropathy, thromboembolisms, and metabolic disorders) being more frequent with nPX (58.5% vs 18.7%; P<.001). None of the geriatric scores (Charlson comorbidity index, Vulnerable Elders Survey [VES-13], Instrumental Activities of Daily Living [IADL], and G8) independently predicted grade 3 to 5 toxic events or treatment discontinuations. No differences in survival between the treatment groups were observed after 22.8 months. CONCLUSIONS: Compared with EC/CMF, treatment with nPX led to more treatment discontinuations and nonhematological toxicities in elderly patients with moderate or high-risk breast cancer.

BACKGROUND AND STUDY AIMS: Hemostatic powders have been introduced to improve the management of gastrointestinal (GI) bleeding and to extend the variety of tools available for emergency endoscopy. The aim of the present pilot study was to evaluate the indication profiles and the short-term outcome of EndoClot. PATIENTS, MATERIALS AND METHODS: In a prospective observational pilot study patients with acute nonvariceal GI bleeding were included. Primary or secondary application of EndoClot was assessed. Hemoglobin, prothrombine time and platelets were documented before and after hemostasis. The efficacy of EndoClot was assessed 72 hours and 1 week after application. RESULTS: Seventy patients with acute GI bleeding were recruited into the study. Eighty-three percent (58/70) of the patients had upper and 17% (12/70) had lower GI bleeding. In the upper GI tract treatment success was achieved in 64% (30/47, 95% confidence interval, 50%-76%) after primary use and in all patients, when used after established techniques had failed (95% confidence interval, 70%-100%). In lower GI bleeding hemostasis was achieved in 83% of cases (10/12, 95% confidence interval 54%-97%). Rebleeding occurred in 11% (8/70), in 10% EndoClot served as a bridge to surgery (7/70). CONCLUSIONS: EndoClot expanded the therapeutic options in the management of GI bleeding. It was applicable as a monotherapy or in combination with other techniques from oozing bleeding type or lower. It was most effective in diffuse or extensive bleeding activity or when access to the bleeding vessel was difficult. EndoClot can be applied as a bridge to surgery when classical methods of hemostasis have failed.