Effectiveness of the lateral pedicled endonasal flap for prevention of restenosis in frontal sinus drillouts.

BACKGROUND: Frontal sinus median drainage according to Draf is an established procedure for achieving maximum drainage of the frontal sinus. Despite great efforts and several modifications, restenosis of the neo-ostium is still a persistent problem. This study presents an approach by implementing local mucosal flaps to prevent restenosis and compares it with the conventional technique without using the flap. METHODS: Description of endonasal, lateral pedicle mucosal flap. A Draf III procedure was performed on 156 patients between 2012 and 2021. Data for 123 of the included patients were retrospectively analyzed in terms of surgical indication, technique, postoperative aftercare and patency of the drainage pathway. The follow-up observation period was between 3 and 24 months. RESULTS: Treatment with the pedicle mucosal flap took place in 86 cases. 37 patients were treated as a control group without this flap. The analysis showed a significant association to the event "total closure of the drainage pathway" for surgical technique, as well as in the case of the presence of an allergy and the existence of Samter's triad. Furthermore, there was a significant association between the onset of "near total closure of the frontal sinus ostium" and Samter';s triad, CRS and revision surgery was involved. CONCLUSIONS: Use of an endonasal lateral pedicle flap for reconstruction of mucosal defects in frontal sinus surgery improves the long-term chances of a patent drainage pathway. Bone exposed by drilling was covered with a local mucosal flap for a faster epithelialization, healing and less scarring.

The HELENA study: Hexvix®-TURB vs. white-light TURB followed by intravesical adjuvant chemotherapy-a prospective randomized controlled open-label multicenter non-inferiority study.

PURPOSE: Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix® TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT. METHODS: Between 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix® TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix® TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113) RESULTS: Median follow-up was 1.81 years. Hexvix® group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; pnon-inferiority = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], pnon-inferiority = 0.493). There was no significant difference in overall survival between both groups (p = 0.257). CONCLUSION: Non-inferiority of Hexvix® TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix®-improved TURB only, confirming its important role in patient treatment.

Immediate versus secondary DIEP flap breast reconstruction: a multicenter outcome study.

PURPOSE: Immediate breast reconstruction (IBR) at the time of mastectomy is gaining popularity, as studies show no negative impact on recurrence or patient survival, but better aesthetic outcome, less psychological distress and lower treatment costs. Using the largest database available in Europe, the presented study compared outcomes and complications of IBR vs. delayed breast reconstruction (DBR). METHODS: 3926 female patients underwent 4577 free DIEP-flap breast reconstructions after malignancies in 22 different German breast cancer centers. The cases were divided into two groups according to the time of reconstruction: an IBR and a DBR group. Surgical complications were accounted for and the groups were then compared. RESULTS: Overall, the rate of partial-(1.0 versus 1.2 percent of cases; p = 0.706) and total flap loss (2.3 versus 1.9 percent of cases; p = 0.516) showed no significant difference between the groups. The rate of revision surgery was slightly, but significantly lower in the IBR group (7.7 versus 9.8 percent; p = 0.039). Postoperative mobilization was commenced significantly earlier in the IBR group (mobilization on postoperative day 1: 82.1 versus 68.7 percent; p < 0.001), and concordantly the mean length of hospital stay was significantly shorter (7.3 (SD3.7) versus 8.9 (SD13.0) days; p < 0.001). CONCLUSION: IBR is feasible and cannot be considered a risk factor for complications or flap outcome. Our results support the current trend towards an increasing number of IBR. Especially in times of economic pressure in health care, the importance of a decrease of hospitalization cannot be overemphasized.

A randomized trial of early endovenous ablation in venous ulceration: a critical appraisal: Original Article: Gohel MS, Heatly F, Liu X et al. A randomized trial of early endovenous ablation in venous ulceration. N Engl J Med 2018; 378:2105-114.

AIM: Gohel et al. aimed to compare early endovenous ablation vs. deferred endovenous ablation of superficial venous reflux with regard to time to healing of venous leg ulcers, rate of healing at 24 weeks, recurrence rate, ulcer-free time and health-related quality of life. SETTING AND DESIGN: This multicentre, parallel-group (ratio 1 : 1), randomized controlled trial was conducted in a vascular surgery department setting at 20 participating centres across the U.K. STUDY EXPOSURE: A total of 450 patients with venous leg ulcers were randomly assigned to receive compression therapy and undergo early endovenous ablation of superficial venous reflux within 2 weeks after randomization (early-intervention group) or to receive compression therapy alone, with consideration of endovenous ablation deferred until after the ulcer was healed or until 6 months after randomization if the ulcer was unhealed (deferred-intervention group). OUTCOMES: The primary outcome was the time to ulcer healing. Secondary outcomes were the rate of ulcer healing at 24 weeks, the rate of ulcer recurrence, the length of time free from ulcers (ulcer-free time) during the first year after randomization, and patient-reported health-related quality of life. TRIAL INTERVENTIONS: Endovenous laser or radiofrequency ablation, ultrasound-guided foam sclerotherapy, or nonthermal, nontumescent methods of treatment (such as cyanoacrylate glue or mechanochemical ablation) were performed either alone or in combination. The treating clinical team determined the method and strategy of endovenous treatment. RESULTS: The time to ulcer healing was shorter in the early-intervention group than in the deferred-intervention group. Furthermore, more patients had healed ulcers with early intervention [hazard ratio for ulcer healing 1·38, 95% confidence interval (CI) 1·13-1·68; P = 0·001]. The median time to ulcer healing was 56 days (95% CI 49-66) in the early-intervention group and 82 days (95% CI 69-92) in the deferred-intervention group. The rate of ulcer healing at 24 weeks was 85·6% in the early-intervention group and 76·3% in the deferred-intervention group. The median ulcer-free time during the first year after trial enrolment was 306 days (interquartile range 240-328) in the early-intervention group and 278 days (interquartile range 175-324) in the deferred-intervention group (P = 0·002). The most common complications were pain and deep vein thrombosis (DVT) (early-intervention group: pain, six of 28; DVT, nine of 28; deferred-intervention group: pain, six of 24; DVT, three of 24). CONCLUSIONS: Gohel et al. conclude that early endovenous ablation of superficial venous reflux results in faster healing of venous leg ulcers than deferred endovenous ablation. Patients assigned to the early-intervention group also had longer ulcer-free time during the first year after randomization.

Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to traumatic choroidal rupture.

BACKGROUND: So far only single cases with short follow-up have been reported on the use of intravitreal anti-VEGF for traumatic choroidal neovascularizations (CNV). This paper reports a large case series of patients with CNV secondary to choroidal rupture after ocular trauma receiving intravitreal anti-VEGF (vascular endothelial growth factor) injections. METHODS: Fifty-four patients with unilateral choroidal rupture after ocular trauma diagnosed between 2000 and 2016 were retrospectively evaluated. Eleven patients with CNV secondary to choroidal rupture were identified. Five eyes with traumatic secondary CNV were treated with anti-VEGF and were systematically analysed. The other 4 patients with inactive CNV underwent watchful observation. RESULTS: Four men and one woman with a mean age of 29 years (SD 12.4; range 19-45) had intravitreal anti-VEGF therapy for traumatic CNV. Another 4 patients with a mean age of 37 years (SD 6.6; range 31-46) presented with inactive CNV and did not receive specific treatment. In all 9 cases the mean interval between the ocular trauma and the diagnosis of CNV was 5.7 months (SD 4.75; range 2-12). In the treatment group per eye 4.2 injections (SD 3.2; range 1-8) were given on average. Four eyes were treated with bevacizumab and one eye with ranibizumab. Regression of CNV was noted in all eyes. In 4 eyes visual acuity (VA) improved, one eye kept stable visual acuity. CONCLUSIONS: Here, we present the up to now largest case series of traumatic CNV membranes treated with anti-VEGF injections with a mean follow-up period of 5 years. Intravitreal anti-VEGF therapy seems to be safe and effective for secondary CNV after choroidal rupture. Compared to exudative age-related macular degeneration fewer injections are needed to control the disease. TRIAL REGISTRATION: Retrospective registration with local ethics committee on 21 March 2019. Trial registration number is 19-1368-104.

Bone block augmentation from the iliac crest for treatment of deep osteochondral defects of the knee resembles biomechanical properties of the subchondral bone.

PURPOSE: Bone block augmentation from the iliac crest can be used for reconstruction of the osteochondral unit to restore the underlying subchondral bone upon restoration of the cartilaginous layer via matrix-induced chondrocyte transplantation. To critically understand the successful restoration of the defect, biomechanical and histological analysis of the implanted bone blocks is required. The aim of the study was to analyse the ability of the bone block technique to restore huge bone defects by mimicking the physiological subchondral zone. METHODS: The experiments were performed using lateral femoral condyles and iliac crest bone grafts from the same cadavers (n = 6) preserved using the Thiel method. CT scans were made to evaluate bone pathology. Bone mineral density of all specimens was evaluated in the femoral head prior to testing. A series of tests were conducted for each pair of specimens. A static compression test was performed using an electro dynamic testing machine with maximal strength and failure behavior analyzed. Biomechanical tests were performed in the medial-lateral direction for iliac crest and for femoral condyles with and without removal of the cartilage layer. Histological analysis was performed on decalcified specimens for comparison of the condyle at lesion site and the graft. RESULTS: No significant difference in failure load could be found for iliac crest (53.3-180.5 N) and femoral condyle samples upon cartilage removal (38.5-175.1 N) (n.s.). The femoral condyles with an intact cartilage layer showed significantly higher loads (118.3-260.4N) compared to the other groups indicating that native or regenerated cartilage can further increase the failure load (p < 0.05). Bone mineral density significantly influenced failure load in all study groups (p < 0.05). Histological similarity of the cancellous bone in the femoral condyle and in the iliac crest was observed. However, within the subchondral zone, there was a higher density of sponge like organized trabeculae in the bone samples from the iliac crest. Tide mark was only detected at the osteochondral interface in femoral condyles. CONCLUSION: This study demonstrated that, bone blocks derived from the iliac crest allow a biomechanical appropriate and stable restoration of huge bony defects by resembling the subchondral zone of the femoral condyle. Therefore, bone augmentation from the iliac crest combined with matrix-induced autologous chondrocyte transplantation seems to be a reasonable method to treat these challenging injuries.

Adherence and health literacy as related to outcome of patients treated for rheumatoid arthritis : Analyses of a large-scale observational study.

BACKGROUND: Disabilities in daily living and quality of life are key endpoints for evaluating the treatment outcome for rheumatoid arthritis (RA). Factors possibly contributing to good outcome are adherence and health literacy. METHODS: The survey included a representative nationwide sample of German rheumatologists and their patients with RA. The physician questionnaire included the disease activity score (DAS28) and medical prescriptions. The patient questionnaire included fatigue (EORTC QLQ-FA13), health assessment questionnaire (HAQ), quality of life (SF-12), health literacy (HELP), and patients' listings of their medications. Adherence was operationalized as follows: patient-reported (CQR5), behavioral (concordance between physicians' and patients' listings of medications), physician-assessed, and a combined measure of physician rating (1 = very adherent, 0 = less adherent) and the match between physicians' prescriptions and patients' accounts of their medications (1 = perfect match, 0 = no perfect match) that yielded three categories of adherence: high, medium, and low. Simple and multiple linear regressions (controlling for age, sex, smoking, drinking alcohol, and sport) were calculated using adherence and health literacy as predictor variables, and disease activity and patient-reported outcomes as dependent variables. RESULTS: 708 pairs of patient and physician questionnaires were analyzed. The mean patient age (73% women) was 60 years (SD = 12). Multiple regression analyses showed that high adherence was significantly associated with 5/7 outcome variables and health literacy with 7/7 outcome variables. CONCLUSION: Adherence and health literacy had weak but consistent effects on most outcomes. Thus, enhancing adherence and understanding of medical information could improve outcome, which should be investigated in future interventional studies.

Health-related quality of life: a retrospective study on local vs. microvascular reconstruction in patients with oral cancer.

BACKGROUND: New medicinal and surgical oncological treatment strategies not only improve overall survival rates but continually increase the importance of Health-Related Quality of Life (HRQOL). The purpose of this retrospective cross-sectional study was to analyze HRQOL of patients with oral squamous cell carcinoma after ablative surgery and to evaluate predictive factors for HRQOL outcome. METHODS: The study included 88 patients with histologically confirmed oral squamous cell carcinoma of whom 42 had undergone local reconstruction (LR) and 46 microvascular reconstruction (MVR). During follow-up, all patients completed the University of Washington Quality of Life Questionnaire (UW-QOL) containing 12 targeted questions about the head and neck. Descriptive analyses were made for the tumor site, the T-stage, and adjuvant therapies. HRQOL was compared between the LR and the MVR group with parametric tests. Further analyses were impact of the tumor site, the T-status, and the time from surgery to survey on HRQOL. Statistics also included multivariate correlations and different interaction effects. RESULTS: HRQOL in the LR group was 'very good' with 84.3 ± 13.7 and 'good' in the MVR group with 73.3 ± 16.5 points. The physical domains swallowing (p = 0.00), chewing (p = 0.00), speech (p = 0.01), taste (p = 0.01), and pain (p = 0.04) were significantly worse in the MVR group. An increase in the T-status had a significant negative effect on swallowing (p = 0.01), chewing (p = 0.01), speech (p = 0.03), recreation (p = 0.05), and shoulder (p = 0.01) in both groups. Regarding the tumor site and subsequent loss of HRQOL, patients with squamous cell carcinoma on the floor of the mouth had significantly worse results in the categories pain (p = 0.002), speech (p = 0.002), swallowing (p = 0.03), activity (p = 0.02), and recreation (p = 0.01) than patients with tumors in the buccal mucosa. Speech (p = 0.03) and pain (p = 0.01) had improved 1 year after surgery. CONCLUSION: Patients with flap reconstruction because of oral squamous cell carcinoma showed very good overall HRQOL. Outcomes for microvascular reconstruction were good, even in the case of larger defects. The T-status is a predictor for HRQOL. Swallowing, chewing, speaking, taste, and pain were the most important issues in our cohort. Implementing HRQOL questionnaires for the assessment of quality of life could further increase the treatment quality of patients with oral cancer.

Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to punctate inner choroidopathy.

PURPOSE: To assess the outcome of patients with choroidal neovascularization (CNV) secondary to punctate inner choroidopathy (PIC) receiving intravitreal anti-VEGF (vascular endothelial growth factor) injections. METHODS: Sixteen eyes of 16 patients diagnosed with CNV secondary to PIC were retrospectively assessed. RESULTS: Eleven women and five men with a mean age of 35 years (SD 11, range 16-56 years) received intravitreal anti-VEGF for PIC-related CNV. On average, 3.5 injections (SD 2.7, range 1-9) were given per eye. Thirteen eyes were treated with bevacizumab, two eyes with ranibizumab and one eye received both substances. The mean follow-up was 15 months (SD 11, range 6-40 months). BCVA improved in eight eyes (mean Δ +2.8 lines), remained stable in four eyes and decreased in four eyes (mean Δ -4.3 lines). CONCLUSIONS: CNV development is a frequent complication of PIC. Intravitreal anti-VEGF therapy seems to be safe and effective for PIC-related CNV.

Screening-relevant age threshold of 70 years and older is a stronger determinant for the choice of adjuvant treatment in breast cancer patients than tumor biology.

PURPOSE: The 70-year threshold determines whether patients are eligible or not for the breast cancer screening program in Germany. It is not known whether this age threshold also influences the choice of adjuvant treatment and ultimate outcome. METHODS: 3463 patients were analyzed from the clinical cancer registry Regensburg (Germany) with primary, non-metastatic invasive breast cancer diagnosed between 2000 and 2012. The distribution of tumor biological subtypes was evaluated in breast cancer patients both in those eligible for screening (ESG, 50-69 years) and those not eligible for screening (NESG, ≥70 years). Local and systemic therapies in different subtypes as well as overall survival (OS) were analyzed. RESULTS: 2171 patients (62.7%) pertained to the ESG and 1292 patients (37.3%) referred to the NESG. The distribution of the common subtypes Luminal A, Luminal B, HER2-like, and Basal-like was comparable in both groups. Treatment varied considerably with less systemic therapies in all subtypes in patients in the NESG. Regarding local therapies, patients in the NESG also received less surgery and less radiotherapy. As to Luminal A patients, best OS was seen in patients receiving endocrine therapy (ET) (7-year OS of 95.6%) and CHT plus ET (7-year OS of 93.1%) in the ESG. In the NESG, best OS was seen in patients receiving CHT plus ET (7-year OS of 95.2%), whereas patients receiving only ET had a 7-year OS of 73.9%. CONCLUSIONS: Despite similar tumor biology, elderly patients are undertreated regarding both systemic and local therapies compared to younger patients, leading to reduced OS.

Photodynamic therapy using intense pulsed light for treating actinic keratoses and photoaged skin of the dorsal hands: a randomized placebo-controlled study.

BACKGROUND: The efficacy of photodynamic therapy (PDT) with intense pulsed light (IPL) has been shown for treating actinic keratoses (AK) and improving photoaged skin on the face but not yet on the dorsal hands. OBJECTIVES: To evaluate the efficacy of PDT with IPL for treating AK of the dorsal hands, inducing neocollagenesis and improving photoaged skin. METHODS: In this prospective, randomized, placebo-controlled, monocentric, within-patient, observer-blinded trial, patients with one to four mild-to-moderate AK on the dorsal hands were randomly allocated to two different treatment groups: methyl aminolaevulinate (MAL) and IPL (λ ≥ 600 nm, 16·2 J cm-2 , three passes, Ellipse Flex PPT) (MAL-IPL) or placebo and IPL (λ ≥ 600 nm, 16·2 J cm-2 , three passes, Ellipse Flex PPT) (placebo-IPL). Patients received three treatments at 6-week intervals, and follow-up was 10 weeks after the last treatment. Thirty-seven patients aged 68·84 ± 9·28 years were randomized. The primary study end points were complete AK clearance per hand and neocollagenesis of subepidermal collagen 10 weeks after the last treatment. RESULTS: Ten weeks after the last treatment, complete AK clearance rates per hand were 54·5% after MAL-IPL and 3·0% after placebo-IPL (P < 0·0001); complete AK clearance rates per lesion were 69% and 15%, respectively (P < 0·001). The thickness of the subepidermal collagen band had increased by 290·6% (± 327·4%, P < 0·001) after MAL-IPL and by 215·5% (± 215·3%, P < 0·001) after placebo-IPL without any significant difference between the two groups. Ratings regarding mottled pigmentation and overall appearance by the blinded investigator were significantly higher for MAL-IPL than for placebo-IPL. Wrinkle size (MAL-IPL, -23·5%, P = 0·006; placebo-IPL, -17·7%, P = 0·010) and skin roughness (MAL-IPL, -18·3%, P < 0·001; placebo-IPL, -12·4%, P = 0·009) were significantly reduced in both groups without any significant difference between the two groups. CONCLUSIONS: On the dorsal hands, MAL-IPL reduced AK more efficaciously than placebo-IPL; both treatment modalities significantly improved photoaged skin.

Daylight photodynamic therapy versus cryosurgery for the treatment and prophylaxis of actinic keratoses of the face - protocol of a multicenter, prospective, randomized, controlled, two-armed study.

BACKGROUND: Photodynamic therapy with daylight (DL-PDT) is efficacious in treating actinic keratosis (AK), but the efficacy of field-directed, repetitive DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has not yet been investigated. METHODS/DESIGN: In this multicenter, prospective, randomized, controlled, two-armed, observer-blinded trial, patients with a minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly allocated to two treatment groups: DL-PDT with methyl aminolevulinate (MAL) and cryosurgery. In the DL-PDT group (experimental group), 5 treatments of the entire face are conducted over the course of 18 months. After preparation of the lesion and within 30 min after MAL application, patients expose themselves to daylight for 2 h. In the control group, lesion-directed cryosurgery is conducted at the first visit and, in the case of uncleared or new AK lesions, also at visits 2 to 5. The efficacy of the treatment is evaluated at visits 2 to 6 by documenting all existing and new AK lesions in the face. Cosmetic results and improvement of photoaging parameters are evaluated by means of a modified Dover scale. Primary outcome parameter is the cumulative number of AK lesions observed between visits 2 and 6. Secondary outcome parameters are complete clearance of AK, new AK lesions since the previous visit, cosmetic results independently evaluated by both patient and physician, patient-reported pain (visual analogue scale), patient and physician satisfaction scores with cosmetic results, and patient-reported quality of life (Dermatology Life Quality Index). Safety parameters are also documented (adverse events and serious adverse events). DISCUSSION: This clinical trial will assess the efficacy of repetitive DL-PDT in preventing AK and investigate possible rejuvenating effects of this treatment. (Trial registration: ClinicalTrials.gov Identifier: NCT02736760). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02736760 . Study Code Daylight_01. EudraCT 2014-005121-13.

Intraoperative clinical testing overestimates the therapeutic window of the permanent DBS electrode in the subthalamic nucleus.

BACKGROUND: Intraoperative test stimulation is established to optimize target localization in STN DBS, but requires a time-consuming awake surgery in off-medication state. The aim of this study was to compare the thresholds of stimulation-induced effects of test stimulation and the permanent electrode. METHODS: Fifty-nine PD patients receiving bilateral STN DBS were clinically examined with stepwise increasing monopolar stimulation during surgery and DBS programming at matched stimulation depths. Thresholds of therapeutic and side effects were obtained from standardized examination protocols. RESULTS: Postoperative stimulation via the permanent electrode caused side effects at a significantly lower threshold than predicted during intraoperative test stimulation (P < 0.001); whereas sufficient therapeutic effects were achieved at significantly higher thresholds (P < 0.001). CONCLUSIONS: Intraoperative testing may lead to an overestimation of the therapeutic window. The two different electrodes lead to distinct spreading of the electric field in the STN and surrounding tissues that causes different volume of tissue activated (VTA). Clinicians involved in DBS surgery and programming should be aware of the differences in both stimulation settings, concerning electrodes geometry, stimulation modes as well as the impact of time. Therapeutic and side effects of permanent stimulation are not predictable by intraoperative test stimulation. Test stimulation may be an orientating test for very low thresholds of side effects instead.

What is the optimal valgus pre-set for intramedullary femoral alignment rods in total knee arthroplasty?

PURPOSE: In total knee arthroplasty (TKA), intramedullary guides are often used for aligning the distal femoral cutting block. Because of the highly varying angles between the mechanical axis and the anatomical femoral axis (AMA), different valgus pre-sets have been recommended. The present study investigated the optimal valgus pre-set (measuring the AMA in long-leg radiographs or at 5°, 6°, 7° or 8° valgus) to align the cutting block perpendicularly to the mechanical axis. METHODS: The AMA was preoperatively measured in weight-bearing long-leg radiographs. After alignment of the cutting block by means of an intramedullary rod, deviation of the block from the mechanical femoral axis was measured with a pinless navigation device. The true AMA (tAMA) was calculated by adding the valgus pre-set of the alignment rod to the deviation measured with the navigation device. Mean deviations between the tAMA and (a) the AMA measured by the surgeon, (b) the AMA calculated with the computer software, (c) 5°, (d) 6°, (e) 7° and (f) 8° valgus pre-sets were measured for each patient. The lowest mean differences were determined. RESULTS: The 40 knees measured showed a mean tAMA of 7.2° valgus (1.7 SD) (range 4°-11.5°). The following mean differences and 95 % limits of agreement were calculated: 2.2 (-1.2, 5.5) to the tAMA for the 5° valgus pre-set, 1.2 (-2.2, 4.5) for 6°, 0.2 (-3.2, 3.5) for 7° and -0.8 (-4.2, 2.5) for 8°. AMA measurements by the surgeon and with the digital medical planning software yielded mean differences of 0.6 (-3.1, 4.3) and 0.4 (-4.1, 4.8), respectively. CONCLUSION: In the present setting, the best mean distal femoral cutting block alignment perpendicular to the mechanical femoral axis could be achieved with a valgus pre-set of 7° and not by measuring the AMA. Nevertheless, we recommend conducting weight-bearing radiographs of the entire leg prior to TKA for easy detection of any anatomical varieties, old fractures, long stems of total hip arthroplasties or cement. However, surgeons must be aware that exact coronal component alignment can only be achieved by navigational devices. LEVEL OF EVIDENCE: Diagnostic study, Level II.

Non-surgical treatment of pubic overload and groin pain in amateur football players: a prospective double-blinded randomised controlled study.

PURPOSE: The incidence of groin pain in athletes is steadily increasing. Symptomatic pubic overload with groin pain and aseptic osteitis pubis represent well-known and frequently misdiagnosed overuse injuries in athletes. This study investigated the benefits of standardised non-surgical treatment for swift return-to-football. METHODS: In a prospective double-blinded controlled study, 143 amateur football players with groin pain as well as radiological signs and clinical symptoms of pubic overload were analysed for 1 year. Two randomised study groups participated in an intensive physical rehabilitation programme, either with or without shock wave therapy. The control group did not participate in any standardised rehabilitation programme but only stopped participating in sports activity. Follow-up examinations took place 1, 3 months and 1 year after the beginning of therapy. Endpoints were visual analogue scale (VAS), functional tests, the time of return-to-football, recurrent complaints and changes in the MR image. RESULTS: Forty-four football players with groin pain and aseptic osteitis pubis were randomised into two study groups; 26 received shock wave therapy, 18 did not. Clinical examination showed pubic overload as a multi-located disease. Players receiving shock wave therapy showed earlier pain relief in the VAS (p < 0.001) and returned to football significantly earlier (p = 0.048) than players without this therapy. Forty-two of 44 players of both study groups returned to football within 4 months after the beginning of therapy and had no recurrent groin pain within 1 year after trauma. Fifty-one players of the control group returned to football after 240 days (p < 0.001), of whom 26 (51%) experienced recurrent groin pain. Follow-up MRI scans did not show any effect of shock wave therapy. CONCLUSION: Non-surgical therapy is successful in treating pubic overload and osteitis pubis in athletes. Shock wave therapy as a local treatment significantly reduced pain, thus enabling return-to-football within 3 months after trauma. Early and correct diagnosis is essential for successful intensive physiotherapy. LEVEL OF EVIDENCE: I.

Multiple exposures to indoor contaminants: Derivation of benchmark doses and relative potency factors based on male reprotoxic effects.

Semi-Volatile Organic Compounds (SVOCs) are commonly present in dwellings and several are suspected of having effects on male reproductive function mediated by an endocrine disruption mode of action. To improve knowledge of the health impact of these compounds, cumulative toxicity indicators are needed. This work derives Benchmark Doses (BMD) and Relative Potency Factors (RPF) for SVOCs acting on the male reproductive system through the same mode of action. We included SVOCs fulfilling the following conditions: detection frequency (>10%) in French dwellings, availability of data on the mechanism/mode of action for male reproductive toxicity, and availability of comparable dose-response relationships. Of 58 SVOCs selected, 18 induce a decrease in serum testosterone levels. Six have sufficient and comparable data to derive BMDs based on 10 or 50% of the response. The SVOCs inducing the largest decrease in serum testosterone concentration are: for 10%, bisphenol A (BMD10 = 7.72E-07 mg/kg bw/d; RPF10 = 7,033,679); for 50%, benzo[a]pyrene (BMD50 = 0.030 mg/kg bw/d; RPF50 = 1630), and the one inducing the smallest one is benzyl butyl phthalate (RPF10 and RPF50 = 0.095). This approach encompasses contaminants from diverse chemical families acting through similar modes of action, and makes possible a cumulative risk assessment in indoor environments. The main limitation remains the lack of comparable toxicological data.

[Outcomes of Stage-Adapted Surgical Treatment of Pleural Empyema]. / Ergebnisse der stadienadaptierten chirurgischen Therapie von Pleuraempyemen.

BACKGROUND: The surgical treatment of pleural empyema should be carried out depending on the stage of the disease and the patient's symptoms. The aim of this study was to evaluate the outcomes of surgical pleural empyema treatment. PATIENTS AND METHODS: Retrospective analysis of all patients with pleural empyema treated surgically between January 2008 and December 2013. The primary endpoint of the study was inpatient lethality. Secondary endpoints included duration of inpatient stay, type of treatment (surgical/conservative), proof of pathogen and type, alteration and duration of antibiotic therapy. RESULTS: Of 359 patients, 0.8 % (n = 3) had stage I empyema, 50.4 % (n = 181) had stage II and 48.7 % (n = 175) had stage III. The most frequent causes (32.4 %) included acute pneumonia (parapneumonic pleural empyema), surgery (usually thoracic) in 18.0 % of cases and previous pneumonia (postpneumonic pleural empyema) in 15.4 %. Surgery was performed in 86 % of cases (operative procedures: open thoracotomy 85 %, VATS 15 %). The average duration of inpatient stay was 20 days for stages II and III. Recovery following VATS was significantly shorter in stage II compared to thoracotomy (p = 0.022). Hospital lethality amounted to 7.0 % (25 patients). The lethality rate was 5.5 % (10/185) in stage II and 8.6 % (15/175) in stage III. Patients with confirmed pathogens had a significantly worse mortality rate across all stages (9.8 %) than patients with no confirmed pathogens (4.0 %, p = 0.034). Age, malignant underlying disease, multiple comorbidities, immunosuppression, a change in antibiotic regimens and sepsis were significant risk factors. CONCLUSION: The inpatient lethality of patients with pleural empyema correlates with the stage of the condition. Positive confirmation of pathogens, sepsis, a higher age, multiple comorbidities, malignant tumour disease, immunosuppression and a change of antibiotics are negative prognostic factors.

4-IHC classification of breast cancer subtypes in a large cohort of a clinical cancer registry: use in clinical routine for therapeutic decisions and its effect on survival.

The aim of the present study was to evaluate to what extent the combination of standard histopathological parameters determines the biology of breast cancer and the effect on therapy and prognosis. The Clinical Cancer Registry Regensburg (Bavaria, Germany) included n = 4,480 female patients with primary, non-metastatic (M0) invasive breast cancer diagnosed between 2000 and 2012. Immuno-histochemical analyses, i.e., estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 (4-IHC), defined the tumor biological subtypes Luminal A, Luminal B, HER2-like, and Basal-like. Subtype-related differences in therapies and overall survival (OS) were analyzed using multivariable statistical methods. 4344 patients (97.0 %) could be classified into the four common tumor biological subtypes. The two most frequent entities were Luminal A (48.4 %), Luminal B (24.8 %), HER2-like (17.8 %), and Basal-like subtype (9.0 %). A multivariable Cox regression model showed that the best 7-year OS was seen in Luminal A patients and that OS of Luminal B and HER2-like patients was comparable (HR = 1.59, P < 0.001 versus HR = 1.51, P = 0.03). Lowest OS was seen in patients with Basal-like tumors (HR = 2.18, P < 0.001). In conclusion, the classification of tumor biological subtypes by the ER, PR, HER2, and Ki-67 biomarkers is practical in routine clinical work. Providing that quality assurance of these markers is ensured, this classification is useful for making therapy decisions in the routine clinical management of breast cancer patients.

Comparing cold-air analgesia, systemically administered analgesia and scalp nerve blocks for pain management during photodynamic therapy for actinic keratosis of the scalp presenting as field cancerization: a randomized controlled trial.

BACKGROUND: Photodynamic therapy (PDT) using methyl aminolaevulinate (MAL) is an effective treatment for extensive actinic keratosis (AK). However, pain is a major side-effect of this therapy. OBJECTIVES: To investigate whether scalp nerve blocks (group 1) provide adequate pain relief during MAL-PDT of the scalp and forehead in 32 men with baldness. METHODS: The patients received intravenous (IV) analgesia [piritramide 7.5 mg IV, plus oral metamizole (40 drops 30 min prior to PDT)] in combination with cold-air analgesia (group 2; IV analgesia) and cold-air analgesia alone (group 3). Maximum pain was evaluated by means of a visual analogue scale (VAS) during and up to 300 min after PDT. Pain during PDT was further analysed according to a pain perception scale. Furthermore, we measured haemodynamics and investigated stress hormone levels in blood samples at different time points. RESULTS: Maximum pain during PDT (primary end point) was significantly reduced in the treatment group receiving scalp nerve blocks (VAS 2.1 ± 1.3) compared with the treatment groups receiving IV analgesia (VAS 7.3 ± 1.1) and cold-air analgesia (VAS 8.4 ± 2.0; P < 0.05). No significant difference was found between groups 2 and 3 with regard to pain relief (P = 0.32). The increase in systolic blood pressure during the first 3 min of PDT was significantly lower for group 1 than for groups 2 and 3 (P < 0.001). No correlation between stress hormone levels and pain were found. CONCLUSIONS: Scalp nerve blocks provide an effective method for pain management during PDT for patients with extensive AK.