Boris Adamietz

Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection.

Introduction MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls. Methods We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR) validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718). Results Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202. Conclusions MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to establish these new biomarkers in clinical use.

Radiotherapy in Early-Stage Dupuytren’s Contracture

Background and Purpose:In early-stage Dupuytren’s contracture, radiotherapy is applied to prevent disease progression. Long-term outcome and late toxicity of the treatment were evaluated in a retrospective analysis.Patients and Methods:Between 12/1982 and 02/2006, 135 patients (208 hands) were irradiated with orthovoltage (120 kV; 20 mA; 4-mm Al filter), in two courses with five daily fractions of 3.0 Gy to a total dose of 30 Gy; separated by a 6- to 8-week interval. The extent of disease was described according to a modified classification of Tubiana et al. Long-term outcome was analyzed at last follow-up between 02/2008 and 05/2008 with a median follow-up of 13 years (range, 2–25 years). Late treatment toxicity and objective reduction of symptoms as change in stage and numbers of nodules and cords were evaluated and used as evidence to assess treatment response.Results:According to the individual stages, 123 cases (59%) remained stable, 20 (10%) improved, and 65 (31%) progressed. In stage N 87% and in stage N/I 70% remained stable or even regressed. In more advanced stages, the rate of disease progression increased to 62% (stage I) or 86% (stage II). 66% of the patients showed a long-term relief of symptoms (i.e., burning sensations, itching and scratching, pressure and tension). Radiotherapy did not increase the complication rate after surgery in case of disease progression and only minor late toxicity (skin atrophy, dry desquamation) could be observed in 32% of the patients. There was no evidence for a second malignancy induced by radiotherapy.Conclusion:After a mean follow-up of 13 years radiotherapy is effective in prevention of disease progression and improves patients’ symptoms in early-stage Dupuytren’s contracture (stage N, N/I). In case of disease progression after radiotherapy, a “salvage” operation is still feasible.Hintergrund und Ziel:Im Frühstadium des Morbus Dupuytren wird die perkutane Radiotherapie eingesetzt mit dem Ziel, die weitere Progression der Erkrankung zu verhindern. In einer aktuellen retrospektiven Analyse wurden der Langzeiterfolg sowie die Nebenwirkungen untersucht.Patienten und Methodik:Im Zeitraum von 12/1982 bis 02/2006 wurden 135 Patienten mit 208 erkrankten Händen am Orthovoltgerät (120 kV; 20 mA; 4-mm-Al-Filter) in zwei Serien (6–8 Wochen Pause) mit je 5 × 3,0 Gy bis zu einer Gesamtdosis von 30 Gy bestrahlt. Die Klassifikation der Erkrankung erfolgte modifiziert nach Tubiana et al. Die Langzeitergebnisse wurden bei einer Nachsorgeuntersuchung zwischen 02/2008 und 05/2008 (mediane Nachbeobachtungszeit 13 Jahre; Spanne 2–25 Jahre) erhoben. Die Spätnebenwirkungen und das Therapieansprechen hinsichtlich der Veränderungen des Erkrankungsstadiums sowie der Anzahl der Knoten und Stränge wurden erfasst.Ergebnisse:Unter Berücksichtigung des Ausgangsstadiums zeigte sich bei 123 Händen (59%) eine Befundstabilität, 20 Hände (10%) verbesserten sich, während 65 Hände (31%) eine Verschlechterung im Stadium erlitten. Bei Patienten im Stadium N konnte bei 87% der Hände und im Stadium N/I bei 70% eine stabile Situation oder eine Stadienverbesserung erreicht werden. In fortgeschritteneren Stadien stieg das Progressionsrisiko auf 62% (Stadium I) bis 86% (Stadium II). 66% der Patienten berichten über eine anhaltende Symptomrückbildung. Die Radiotherapie führte nicht zu einer erhöhten Komplikationsrate nach einer bei Progression durchgeführten Operation; es zeigten sich nur geringgradige Spätnebenwirkungen (Hautatrophie oder Trockenheit mit Schuppung) bei 32% der Patienten.Schlussfolgerung:Auch nach einer medianen Nachbeobachtungszeit von 13 Jahren erweist sich die Radiotherapie als effektive Maßnahme zur Verhinderung einer weiteren Progression in den Frühstadien der Erkrankung (Stadium N und N/I). Im Fall einer Progression ist eine „Salvage“-Operation ohne erhöhte Nebenwirkungen möglich.

Radiotherapy in early-stage Dupuytren's contracture. Long-term results after 13 years.

Background and Purpose:In early-stage Dupuytren’s contracture, radiotherapy is applied to prevent disease progression. Long-term outcome and late toxicity of the treatment were evaluated in a retrospective analysis.Patients and Methods:Between 12/1982 and 02/2006, 135 patients (208 hands) were irradiated with orthovoltage (120 kV; 20 mA; 4-mm Al filter), in two courses with five daily fractions of 3.0 Gy to a total dose of 30 Gy; separated by a 6- to 8-week interval. The extent of disease was described according to a modified classification of Tubiana et al. Long-term outcome was analyzed at last follow-up between 02/2008 and 05/2008 with a median follow-up of 13 years (range, 2–25 years). Late treatment toxicity and objective reduction of symptoms as change in stage and numbers of nodules and cords were evaluated and used as evidence to assess treatment response.Results:According to the individual stages, 123 cases (59%) remained stable, 20 (10%) improved, and 65 (31%) progressed. In stage N 87% and in stage N/I 70% remained stable or even regressed. In more advanced stages, the rate of disease progression increased to 62% (stage I) or 86% (stage II). 66% of the patients showed a long-term relief of symptoms (i.e., burning sensations, itching and scratching, pressure and tension). Radiotherapy did not increase the complication rate after surgery in case of disease progression and only minor late toxicity (skin atrophy, dry desquamation) could be observed in 32% of the patients. There was no evidence for a second malignancy induced by radiotherapy.Conclusion:After a mean follow-up of 13 years radiotherapy is effective in prevention of disease progression and improves patients’ symptoms in early-stage Dupuytren’s contracture (stage N, N/I). In case of disease progression after radiotherapy, a “salvage” operation is still feasible.Hintergrund und Ziel:Im Frühstadium des Morbus Dupuytren wird die perkutane Radiotherapie eingesetzt mit dem Ziel, die weitere Progression der Erkrankung zu verhindern. In einer aktuellen retrospektiven Analyse wurden der Langzeiterfolg sowie die Nebenwirkungen untersucht.Patienten und Methodik:Im Zeitraum von 12/1982 bis 02/2006 wurden 135 Patienten mit 208 erkrankten Händen am Orthovoltgerät (120 kV; 20 mA; 4-mm-Al-Filter) in zwei Serien (6–8 Wochen Pause) mit je 5 × 3,0 Gy bis zu einer Gesamtdosis von 30 Gy bestrahlt. Die Klassifikation der Erkrankung erfolgte modifiziert nach Tubiana et al. Die Langzeitergebnisse wurden bei einer Nachsorgeuntersuchung zwischen 02/2008 und 05/2008 (mediane Nachbeobachtungszeit 13 Jahre; Spanne 2–25 Jahre) erhoben. Die Spätnebenwirkungen und das Therapieansprechen hinsichtlich der Veränderungen des Erkrankungsstadiums sowie der Anzahl der Knoten und Stränge wurden erfasst.Ergebnisse:Unter Berücksichtigung des Ausgangsstadiums zeigte sich bei 123 Händen (59%) eine Befundstabilität, 20 Hände (10%) verbesserten sich, während 65 Hände (31%) eine Verschlechterung im Stadium erlitten. Bei Patienten im Stadium N konnte bei 87% der Hände und im Stadium N/I bei 70% eine stabile Situation oder eine Stadienverbesserung erreicht werden. In fortgeschritteneren Stadien stieg das Progressionsrisiko auf 62% (Stadium I) bis 86% (Stadium II). 66% der Patienten berichten über eine anhaltende Symptomrückbildung. Die Radiotherapie führte nicht zu einer erhöhten Komplikationsrate nach einer bei Progression durchgeführten Operation; es zeigten sich nur geringgradige Spätnebenwirkungen (Hautatrophie oder Trockenheit mit Schuppung) bei 32% der Patienten.Schlussfolgerung:Auch nach einer medianen Nachbeobachtungszeit von 13 Jahren erweist sich die Radiotherapie als effektive Maßnahme zur Verhinderung einer weiteren Progression in den Frühstadien der Erkrankung (Stadium N und N/I). Im Fall einer Progression ist eine „Salvage“-Operation ohne erhöhte Nebenwirkungen möglich.

Characterizing mammographic images by using generic texture features

IntroductionAlthough mammographic density is an established risk factor for breast cancer, its use is limited in clinical practice because of a lack of automated and standardized measurement methods. The aims of this study were to evaluate a variety of automated texture features in mammograms as risk factors for breast cancer and to compare them with the percentage mammographic density (PMD) by using a case-control study design.MethodsA case-control study including 864 cases and 418 controls was analyzed automatically. Four hundred seventy features were explored as possible risk factors for breast cancer. These included statistical features, moment-based features, spectral-energy features, and form-based features. An elaborate variable selection process using logistic regression analyses was performed to identify those features that were associated with case-control status. In addition, PMD was assessed and included in the regression model.ResultsOf the 470 image-analysis features explored, 46 remained in the final logistic regression model. An area under the curve of 0.79, with an odds ratio per standard deviation change of 2.88 (95% CI, 2.28 to 3.65), was obtained with validation data. Adding the PMD did not improve the final model.ConclusionsUsing texture features to predict the risk of breast cancer appears feasible. PMD did not show any additional value in this study. With regard to the features assessed, most of the analysis tools appeared to reflect mammographic density, although some features did not correlate with PMD. It remains to be investigated in larger case-control studies whether these features can contribute to increased prediction accuracy.

Contrast-enhanced T1-weighted fluid-attenuated inversion-recovery BLADE magnetic resonance imaging of the brain: an alternative to spin-echo technique for detection of brain lesions in the unsedated pediatric patient?

RATIONALE AND OBJECTIVES We compared contrast-enhanced T1-weighted magnetic resonance (MR) imaging of the brain using different types of data acquisition techniques: periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER, BLADE) imaging versus standard k-space sampling (conventional spin-echo pulse sequence) in the unsedated pediatric patient with focus on artifact reduction, overall image quality, and lesion detectability. MATERIALS AND METHODS Forty-eight pediatric patients (aged 3 months to 18 years) were scanned with a clinical 1.5-T whole body MR scanner. Cross-sectional contrast-enhanced T1-weighted spin-echo sequence was compared to a T1-weighted dark-fluid fluid-attenuated inversion-recovery (FLAIR) BLADE sequence for qualitative and quantitative criteria (image artifacts, image quality, lesion detectability) by two experienced radiologists. Imaging protocols were matched for imaging parameters. Reader agreement was assessed using the exact Bowker test. RESULTS BLADE images showed significantly less pulsation and motion artifacts than the standard T1-weighted spin-echo sequence scan. BLADE images showed statistically significant lower signal-to-noise ratio but higher contrast-to-noise ratios with superior gray-white matter contrast. All lesions were demonstrated on FLAIR BLADE imaging, and one false-positive lesion was visible in spin-echo sequence images. CONCLUSION BLADE MR imaging at 1.5 T is applicable for central nervous system imaging of the unsedated pediatric patient, reduces motion and pulsation artifacts, and minimizes the need for sedation or general anesthesia without loss of relevant diagnostic information.

Mammographic density as a risk factor for breast cancer in a German case-control study.

Mammographic percent density (MD) is recognized as one of the strongest risk factors associated with breast cancer. This matched case–control study investigated whether MD represents an independent risk factor. Mammograms were obtained from 1025 breast cancer patients and from 520 healthy controls. MD was measured using a quantitative computer-based threshold method (0–100%). Breast cancer patients had a higher MD than healthy controls (38 vs. 32%, P<0.01). MD was significantly higher in association with factors such as age over 60 years, body mass index (BMI) of 25–30 kg/m2, nulliparity or low parity (one to two births). Average MD was inversely associated with age, BMI, parity and positively associated with age at first full-term pregnancy. MD was higher in women with at least one first-degree relative affected, but only among patients and not in the group of healthy controls (P<0.01/P=0.61). In women with an MD of 25% or more, the risk of breast cancer was doubled compared with women with an MD of less than 10% (odds ratio: 2.1; 95% confidence interval: 1.3–3.4; P<0.01); in the postmenopausal subgroup, the risk was nearly tripled (odds ratio: 2.7; 95% confidence interval: 1.6–4.7; P<0.001). This study provides further evidence that MD is an important risk factor for breast cancer. These results indicate strong associations between MD and the risk of breast cancer in a matched case–control study in Germany.

Die Radiotherapie des Morbus Dupuytren im Frühstadium Langzeitresultate nach einer medianen Nachbeobachtungszeit von 10 Jahren

PURPOSE In early stage Dupuytrens contracture radiotherapy was applied to prevent disease progression. Long-term results and late toxicity of this treatment were evaluated in a retrospective analysis. PATIENTS AND METHODS Between 1982 and 1994, 99 patients (176 hands) received orthovoltage radiotherapy, which consisted of two courses with 5 x 3 Gy (total dose: 30 Gy, daily fractionated; 120 kV, 4 mm Al), separated by a 6 to 8-week pause. The Dupuytrens contracture was staged according to the classification of Tubiana et al. The long-term outcome was analyzed at last follow-up between July and November 1999. The median follow-up was 10 years (range 7-18 years). Late toxicity was assessed using the LENT-SOMA criteria. RESULTS In Stage N 84% and Stage N/I 67% of cases remained stable. 65% of the cases in Stage I and 83% in Stage II showed progressive nodules and cords. In case of progression we saw no complications after a second radiotherapy or salvage operation. CONCLUSION Radiotherapy effectively prevents disease progression for early stage Dupuytrens contracture (Stage N, N/I). Moreover, in case of disease progression despite radiotherapy salvage surgery is still feasible.Hintergrund: Im Frühstadium des Morbus Dupuytren wird die externe Radiotherapie mit dem Ziel eingesetzt, den progressiven Verlauf der Erkrankung zu verhindern. Eine aktuelle Langzeitverlaufskontrolle soll die Ergebnisse und Nebenwirkungen der Radiotherapie darstellen. Patienten und Methode: Wir untersuchten 99 Patienten (176 Hände), welche sich von 1982–1994 einer Radiotherapie an unserer Klinik unterzogen. Jeder Patient erhielt zwei Serien einer Radiotherapie mit jeweils 5 × 3 Gy (Gesamtdosis 30 Gy, 120 kV, 4 mm Al, Bestrahlungspause von 6–8 Wochen nach 15 Gy). Die Beugekontraktur wurde nach Tubiana et al. eingeteilt. Von Juli bis November 1999 erfolgte nach einer medianen Nachbeobachtungszeit von 10 Jahren (7–18 Jahre) eine Kontrolluntersuchung. Die Nebenwirkungen wurden nach den LENT-SOMA-Kriterien eingestuft. Ergebnisse: Im Stadium N blieben 84% und im Stadium N/I 67% stabil oder zeigten eine Regression. Dagegen stieg ab dem Stadium I die Progressionsrate auf 65% und im Stadium II auf 83% an. Eine “Salvage”-Operation erfolgte bei 29 Patienten, ohne dass Wundheilungsstörungen beobachtet wurden. Schlussfolgerung: Die Radiotherapie stellt in den Frühstadien (Stadium N, N/I) der Dupuytrenschen Kontraktur auch langfristig eine effektive und sichere Methode dar. Bei Therapieversagern ist eine spätere Operation möglich.Purpose: In early stage Dupuytrens contracture radiotherapy was applied to prevent disease progression. Long-term results and late toxicity of this treatment were evaluated in a retrospective analysis. Patients and Methods: Between 1982 and 1994, 99 patients (176 hands) received orthovoltage radiotherapy, which consisted of two courses with 5 × 3 Gy (total dose: 30 Gy, daily fractionated; 120 kV, 4 mm Al), separated by a 6 to 8-week pause. The Dupuytrens contracture was staged according to the classification of Tubiana et al. The long-term outcome was analyzed at last follow-up between July and November 1999. The median follow-up was 10 years (range 7–18 years). Late toxicity was assessed using the LENT-STOMA criteria. Results: In Stage N 84% and Stage N/I 67% of cases remained stable. 65% of the cases in Stage I and 83% in Stage II showed progressive nodules and cords. In case of progression we saw no complications after a second radiotherapy or salvage operation. Conclusion: Radiotherapy effectively prevents disease progression for early stage Dupuytrens contracture (Stage N, N/I). Moreover, in case of disease progression despite radiotherapy salvage surgery is still feasible.

Association of mammographic density with hormone receptors in invasive breast cancers: results from a case-only study.

For many breast cancer (BC) risk factors, there is growing evidence concerning molecular subtypes for which the risk factor is specific. With regard to mammographic density (MD), there are inconsistent data concerning its association with estrogen receptor (ER) and progesterone receptor (PR) expression. The aim of our study was to analyze the association between ER and PR expression and MD. In our case‐only study, data on BC risk factors, hormone receptor expression and MD were available for 2,410 patients with incident BC. MD was assessed as percent MD (PMD) using a semiautomated method by two readers for every patient. The association of ER/PR and PMD was studied with multifactorial analyses of covariance with PMD as the target variable and including well‐known factors that are also associated with MD, such as age, parity, use of hormone replacement therapy, and body mass index (BMI). In addition to the commonly known associations between PMD and age, parity, BMI and hormone replacement therapy, a significant inverse association was found between PMD and ER expression levels. Patients with ER‐negative tumors had an average PMD of 38%, whereas patients with high ER expression had a PMD of 35%. A statistical trend toward a positive association between PMD and PR expression was also seen. PMD appears to be inversely associated with ER expression and may correlate positively with PR expression. These effects were independent of other risk factors such as age, BMI, parity, and hormone replacement therapy, possibly suggesting other pathways that mediate this effect.

New diagnostic criteria in real-time elastography for the assessment of breast lesions.

PURPOSE Elastography is a new ultrasonographic method that has been examined as a diagnostic tool for breast lesions. This study was intended to create and define new elastographic criteria allowing assessment of whether breast lesions are malignant or benign. MATERIALS AND METHODS 217 patients with a total of 245 breast lesions of unknown malignancy underwent ultrasound examination. The new eSie Touch Elasticity Imaging technology (Siemens, Erlangen, Germany) was used with a 10-MHz linear transducer (Acuson Antares). Lesions were examined using B-mode and real-time elastography (RTE). Each lesion was histologically assessed by core biopsy. Five RTE characteristics were examined: elasticity proportion (EP), different location on RTE in comparison with B-mode (MV), different contrast patterns (SOS), dorsal lesion limitation visibility and different size on RTE in comparison with B-mode. RESULTS 54 malignant lesions (54 %) appeared inelastic, in contrast to the benign control group (34.5 %; P = 0.001). A completely elastic pattern was visible in 10 malignant (10 %) and 39 benign lesions (26.9 %). MV was identified in 23 cases, with 22 of the lesions being malignant and one benign. The SOS was negative in 89 malignant lesions (89 %) and positive in 100 benign lesions. The dorsal lesion limitation was visible on RTE without B-mode in 88 malignant lesions (88 %) and 27 benign lesions (18.6 %). The size was assessed as larger in 45 malignant lesions (45 %) and seven benign lesions (4.8 %). CONCLUSION SOS and a larger tumor size on RTE are specific characteristics of malignant breast lesions. EP, MV and distal mass border are further helpful signs to assess the malignancy of tumors.

Bestrahlung beim Impingementsyndrom des Schultergelenks

Hintergrund und Ziel:Bisher wurden die degenerativen Schultergelenkerkrankungen unter dem Überbegriff „Periarthritis humeroscapularis“ zusammengefasst. Heute differenziert man die Erkrankungen ätiopathologisch als primäres und sekundäres Impingementsyndrom: Einengung des Subakromialraums durch anatomische knöcherne Formvarianten als primäres Impingementsyndrom und durch unter dem Schulterdach durchziehende nichtknöcherne Strukturen als sekundäres Impingementsyndrom. Diese Arbeit zielt darauf ab, die differenzierte Diagnose zur Therapieindikation zu stellen und die Therapieergebnisse entsprechend dem alters- und geschlechtsadaptierten Score nach Constant zu bewerten.Patienten und Methodik:Von August 1999 bis September 2002 wurden insgesamt 102 Patienten mit 115 symptomatischen Schultergelenken behandelt. Alle Schultergelenke erhielten jeweils zwei Behandlungsserien (6 × 0,5 Gy Einzeldosis) zwei- bis dreimal pro Woche in Orthovolttechnik bis zu einer Gesamtdosis von 6,0 Gy (250 kV, 15 mAs, 1-mm-Cu-Filter). Die zweite Behandlungsserie folgte nach einer 6-wöchigen Pause. Die Schultergelenke wurden vor Bestrahlung, 6 Wochen nach der zweiten Behandlungsserie und abschließend im Median 18 Monate nach Behandlungsende untersucht.Ergebnisse:Bei 94/115 Schultergelenken (82%) bestand nach 18-monatiger Verlaufskontrolle eine Beschwerdebesserung. Im Therapieansprechen fand sich ein signifikanter Unterschied zwischen dem sekundären Impingement und dem primären bzw. Non-Impingement. Ein gutes Therapieansprechen war bei der Tendinosis calcarea, Bursitis subdeltoidea und Tendovaginitis der langen Bizepssehne wie auch der Capsulitis adhaesiva zu beobachten.Schlussfolgerung:Die Erkrankungen, die als sekundäres Impingementsyndrom zusammengefasst sind, sprechen auf eine Radiotherapie sehr gut an, weniger gut reagiert das primäre Impingementsyndrom, und kein Einfluss findet sich bei der kompletten Rotatorenmanschettenruptur und akuten Verletzungen am Schultergelenk.Background and Purpose:Up to now, degenerative shoulder diseases were summarized by the term “periarthritis humeroscapularis”. Actual shoulder diseases can be differentiated etiopathologically according to a primary and secondary impingement syndrome. Narrowing of the subacromial space, which is caused by an osseous shape variant, leads to primary impingement. Secondary impingement develops, when the subacromial space is reduced by swelling tissue below the osseous shoulder roof. This study aimed for the exact diagnosis to indicate therapy and to classify the results according to the Constant score.Patients and Methods:From August 1999 to September 2002, 102 patients with 115 shoulder joint conditions underwent radiation therapy (RT). All joints received two RT series (6 × 0.5 Gy/series) applied in two to three weekly fractions, totaling a dosage of 6.0 Gy (250 kV, 15 mAs, 1-mm Cu filter). The second RT course started 6 weeks after the end of the first. 115 shoulders were examined before RT, 6 weeks after the second RT course and, finally, during the follow-up from January to May 2003.Results:Pain relief was achieved in 94/115 shoulder joints (82%) after 18-month follow-up (median). A significant difference existed between secondary impingement and primary/non-impingement according to response. Tendinosis calcarea, bursitis subdeltoidea, tendovaginitis of the long biceps tendon, and capsulitis adhaesiva responded well to therapy.Conclusion:Shoulder diseases of secondary impingement demonstrate a good response to RT. Less or no benefit was found in primary impingement syndrome or complete rotator cuff disruption and acute shoulder injuries, respectively.