Action of antimicrobial photodynamic therapy on heterotypic biofilm: <Emphasis Type="Italic">Candida albicans</Emphasis> and <Emphasis Type="Italic">Bacillus atrophaeus</Emphasis>

The increase in survival and resistance of microorganisms organized in biofilms demonstrates the need for new studies to develop therapies able to break this barrier, such as photodynamic therapy, which is characterized as an alternative, effective, and non-invasive treatment. The objective was to evaluate in vitro the effect of antimicrobial photodynamic therapy on heterotypic biofilms of Candida albicans and Bacillus atrophaeus using rose bengal (12.5 μM) and light-emitting diode (LED) (532 nm and 16.2 J). We used standard strains of B. atrophaeus (ATCC 9372) and C. albicans (ATCC 18804). The biofilm was formed in the bottom of the plate for 48 h. For the photodynamic therapy (PDT) experimental groups, we added 100 μL of rose bengal with LED (P+L+), 100 μL of rose bengal without LED (P+L?), 100 μL of NaCl 0.9 % solution with LED (P?L+), and a control group without photosensitizer or LED (P?L?). The plates remained in agitation for 5 min (pre-irradiation) and were irradiated with LED for 3 min, and the biofilm was detached using an ultrasonic homogenizer for 30 s. Serial dilutions were plated in BHI agar and HiChrom agar and incubated at 37 °C/48 h. There was a reduction of 33.92 and 29.31 % of colony-forming units per milliliter (CFU/mL) for C. albicans and B. atrophaeus, respectively, from the control group to the group subjected to PDT. However, statistically significant differences were not observed among the P+L+, P+L?, P?L+, and P?L? groups. These results suggest that antimicrobial photodynamic therapy using rose bengal (12.5 μM) with a pre-irradiation period of 5 min and LED for 3 min was not enough to cause a significant reduction in the heterotypic biofilms of C. albicans and B. atrophaeus.     

Time-dependent antimicrobial effect of photodynamic therapy with TONS 504 on <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>

Pseudomonas aeruginosa (P. aeruginosa) is a major cause of infectious keratitis, which itself is a major cause of blindness worldwide. We have now evaluated the time-dependent effectiveness of photodynamic antimicrobial chemotherapy (PACT) with the chlorin derivative TONS 504 and a light-emitting diode (LED) on P. aeruginosa in vitro. PACT with TONS 504 (10 mg/L) and irradiation (30 J/m²) by an LED device that delivers light centered on a wavelength of 660 nm was applied to 1?×?10⁶ colony-forming units of P. aeruginosa in liquid medium. The bacteria were then cultured at 37 °C for various times before assay of viability by determination of colony formation on agar plates. The effect of a second irradiation at 3 h after the initial LED exposure was also examined. Bacterial growth was markedly inhibited between 3 and 9 h after PACT with TONS 504, with the maximal effect being apparent at 3 h. Furthermore, a second exposure to LED irradiation at 3 h after the first treatment enhanced the inhibitory effect on bacterial growth. PACT with TONS 504 thus inhibited the growth of P. aeruginosa in a time-dependent manner, and an additional irradiation exposure applied 3 h after the first LED treatment greatly increased the effectiveness of PACT. This antibacterial system thus warrants further evaluation with regard to its potential effectiveness for the treatment of infectious keratitis.     

Curcumin-mediated anti-microbial photodynamic therapy against <Emphasis Type="Italic">Candida dubliniensis</Emphasis> biofilms

The purpose of this study was to evaluate the effectiveness of anti-microbial photodynamic therapy (aPDT) mediated by curcumin (Cur) associated with LED light against biofilms of Candida dubliniensis, and further, investigate cellular uptake and drug penetration through the biofilms under confocal laser scanning microscopy (CLSM). Four C. dubliniensis strains were tested: three clinical isolates from HIV-positive patients and one reference strain (CBS 7987). Biofilms were treated with three Cur concentrations (20.0, 30.0, and 40.0 μM). All samples were incubated in the dark for 20 min and exposed to a 5.28 J/cm² of LED light fluence. Additional samples of each strain were treated either with Cur or LED light only. Control samples had neither Cur nor light. After aPDT, results were read using the XTT salt reduction method. The data were statistically analyzed by two-way ANOVA followed by Games-Howell post-hoc test (α?=?0.05). Confocal laser scanning microscopy was used to verify both the uptake of Cur by yeast cells and its penetration through the biofilm. The results showed that aPDT promoted significant reduction on the metabolism of the biofilm-organized cells of C. dubliniensis. Further, while Cur was rapidly taken up by C. dubliniensis cells, a longer time interval was required to allow Cur penetration into biofilm cells. Based on these results, aPDT associating LED and Cur presents promising potential on fungal control of biofilms of C. dubliniensis.     

Photodynamic inactivation in the expression of the <Emphasis Type="Italic">Candida albicans</Emphasis> genes ALS3, HWP1, BCR1, TEC1, CPH1, and EFG1 in biofilms

The objective of this study was to evaluate the effects of photodynamic inactivation (PDI) on Candida albicans biofilms, evaluating its effects on gene expression of ALS3, HWP1, BCR1, TEC1, CPH1, and EFG1 by yeast. Three samples of C. albicans were used in this study: a clinical sample from a patient with HIV (39S), a clinical sample from a patient with denture stomatitis lesion (Ca30), and a standard strain ATCC 18804. The quantification of gene expression was related to the production of those genes in the samples referred above using quantitative polymerase chain reaction (qPCR) assay in real time. The photosensitizer methylene blue at 300 uM and erythrosine at 400 uM, sensitized with low-power laser (visible red, 660 nm) and green LED (532 nm), respectively, were used for PDI. Four groups of each sample and PDI protocol were evaluated: (a) P+L+: sensitization with the photosensitizer and irradiation with light, (b) P+L?: only treatment with the photosensitizer, (c) P?L+: only irradiation with light, and (d) P?L?: without sensitization with the dye and absence of light. The results were analyzed by t test, with a significance level of 5%. The photodynamic inactivation was able to reduce the expression of all genes for both treatments, laser and LED. The fold-decrease for the genes ALS3, HWP1, BCR1, TEC1, CPH1, and EFG1 were 0.73, 0.39, 0.77, 0.71, 0.67, and 0.60 for laser, respectively, and 0.66, 0.61, .050, 0.43, 0.54, and 0.66 for LED, respectively. It could be concluded that PDI showed a reduction in the expression of C. albicans genes, suggesting its virulence decrease.     

Evaluation of the theoretical optimal angle of the tibial tunnel in transtibial anatomic posterior cruciate ligament reconstruction by computed tomography

Background

“Killer turn” effect is a critical explanation for the recurrent posterior laxity following transtibial posterior cruciate ligament (PCL) reconstruction, which affected by the angle of the tibial tunnel. Meanwhile, excessive tunnel angle would have an adverse impact on the healing of tendon to bone. The purpose was to evaluate the theoretical optimal angle of the tibial tunnel in transtibial anatomic PCL reconstruction.

Methods

The measurements were performed on CT sagittal plane, including the thickness of cancellous bone (L1), the theoretical optimal angle of the tibial tunnel (TOA, which was measured between tibial plateau and the extension cord connecting the center of PCL insertion site with a point 5?mm superior from marrow cavity vertex), L2 - the distance from anterior tunnel aperture to anterior end of tibial plateau, L3 - the distance from anterior tunnel aperture to tibial tuberosity (lowest edge of patellar ligament attachment).

Results

The value of TOA and L3 were 35.4?±?7.9 ° and 26.8?±?11.4?mm, respectively. L1 and L2 were higher in males than females (L1, P?= 0.002; L2, P?= 0.046). Regarding age, L1, TOA, L2 and L3 were higher in the 46–60?years group than 31–45?years group (P =?0.02, P =?0.001, P =?0.038, P =?0.032, respectively). With regard to height, L1 was lower in group I - <?1.66?m than group II - 1.66 to 1.75?m and group III -?>?1.75?m (I v II, P =?0.015, I v III, P =?0.026). L2 was also lower in group I than group II and group III (I v II, P =?0.026, I v III, P =?0.006). TOA and L3 showed no significant differences among sex and height groups (P?>?0.05).

Conclusions

TOA (35.4 °?±?7.9 °) and L3 (26.8?±?11.4?mm) could be used as a reference for ideal tibial tunnel placement in transtibial anatomic PCL reconstruction, so as to prevent recurrent PCL laxity and ensure good graft healing. However, further clinical validation is needed.

     

Shoulder periprosthetic joint infection caused by <Emphasis Type="Italic">Propionibacterium acnes</Emphasis>

Background

Propionibacterium acnes is increasingly recognized as an important cause of shoulder periprosthetic joint infection (PJI). We performed a retrospective cohort study of P. acnes shoulder PJI to analyze the clinical, diagnostic, and treatment characteristics.

Methods

Patients diagnosed with shoulder PJI caused by P. acnes were retrospectively analyzed in two university hospitals. Patient data were retrieved through chart review. The outcome was evaluated at patient follow-up visits.

Results

The study included 20 patients with shoulder PJI (median age, 65 years; range, 54–77 years); 75 % were males. The median time from prosthesis implantation to diagnosis of PJI was 34 months (range, 2–60 months). Most PJI (55?%) were diagnosed >24 months after arthroplasty, followed by delayed manifestation 3–24 months after arthroplasty in 30?%. The diagnosis of PJI was preoperatively confirmed in 50?% of patients and suspected in 20 %. Persistent pain was present in 90?%, local signs of inflammation in 60?%, and radiological signs of loosening in 70 % of patients. P. acnes was cultured in joint aspirate in 33?%, periprosthetic tissue in 60?%, and sonication fluid in 89?% of patients. In four patients, coinfection with coagulase-negative staphylococci was found. One-stage prosthesis exchange was performed in four patients (20?%) and two-stage exchange in 15 patients (75?%); in one patient the prosthesis was not re-implanted. After a median follow-up of 26 months (range, 12–47 months), 18 patients (90?%) showed no signs or symptoms of infection.

Conclusion

P. acnes PJI typically manifested several years after implantation. In 30?% of patients, PJI was not suspected before surgery. In patients with persistent pain or prosthesis loosening, low-grade PJI should be excluded, including infection caused by P. acnes.

     

In vitro evaluation of photodynamic therapy using curcumin on <Emphasis Type="Italic">Leishmania majo</Emphasis>r and <Emphasis Type="Italic">Leishmania braziliensis</Emphasis>

Cutaneous leishmaniasis is an infectious disease caused by the Leishmania protozoan. The conventional treatment is long-lasting and aggressive, in addition to causing harmful effect. Photodynamic therapy has emerged as a promising alternative treatment, which allows local administration with fewer side effects. This study investigated the photodynamic activity of curcumin on Leishmania major and Leishmania braziliensis promastigote. Both species were submitted to incubation with curcumin in serial dilutions from 500 μg/ml up to 7.8 μg/ml. Control groups were kept in the dark while PDT groups received a fluency of 10 J/cm² at 450 nm. Mitochondrial activity was assessed by MTT assay 18 h after light treatment, and viability was measured by Trypan blue dye exclusion test. Morphological alterations were observed by Giemsa staining. Confocal microscopy showed the uptake of curcumin by both tested Leishmania species. Mitochondrial activity was inconclusive to determine viability; however, Trypan blue test was able to show that curcumin photodynamic treatment had a significant effect on viability of parasites. The morphology of promastigotes was highly affected by the photodynamic therapy. These results indicated that curcumin may be a promising alternative photosensitizer, because it presents no toxicity in the dark; however, further tests in co-culture with macrophages and other species of Leishmania should be conducted to determine better conditions before in vivo tests are performed.     

Laser and LED phototherapy on midpalatal suture after rapid maxilla expansion: Raman and histological analysis

The aim of this study was to analyze the effect of laser or LED phototherapy on the acceleration of bone formation at the midpalatal suture after rapid maxilla expansion. Forty-five rats were divided into groups at 7 days (control, expansion, expansion and laser irradiation, and expansion and LED irradiation) and into 14 days (expansion, expansion and laser in the 1st week, expansion and LED in the 1st week, expansion and laser in the 1st and 2nd weeks, expansion and LED in the 1st and 2nd weeks). Laser/LED irradiation occurred every 48 h. Expansion was accomplished with a spatula and maintained with a triple helicoid of 0.020-in stainless steel orthodontic wire. A diode laser (λ780 nm, 70 mW, spot of 0.04 cm², t?=?257 s, SAEF of 18 J/cm²) or a LED (λ850?±?10 nm, 150?±?10 mW, spot of 0.5 cm², t?=?120 s, SAEF of 18 J/cm²) was applied in one point in the midpalatal suture immediately behind the upper incisors. Raman spectroscopy and histological analyses of the suture region were carried and data was submitted to statistical analyses (p?≤?0.05). Raman spectrum analysis demonstrated that irradiation increases hydroxyapatite in the midpalatal suture after expansion. In the histological analysis of various inflammation, there was a higher production of collagen and osteoblastic activity and less osteoclastic activity. The results showed that LED irradiation associated to rapid maxillary expansion improves bone repair and could be an alternative to the use of laser in accelerating bone formation in the midpalatal suture.     

The efficacy of bipolar sealer on blood loss in spine surgery: a meta-analysis

Objective

The purpose of this meta-analysis of randomized controlled trials (RCTs) and non-RCTs was to gather data to evaluate the efficacy and safety of bipolar sealer versus standard electrocautery in the management of spinal disease.

Methods

The electronic databases including Embase, PubMed and Cochrane library were searched to identify relevant studies published from the time of the establishment of these databases up to January 2017. The primary outcomes were total blood loss, requirement of transfusion (rate and amount), and operation time. The secondary outcomes were length of hospital stay and postoperative wound infection. Data analysis was conducted with RevMan 5.3 software.

Results

A total of five studies involving 500 patients (261 patients in the BS group and 239 in the control group) were included in the meta-analysis. The pooled results revealed that application of bipolar sealer could decrease the total blood loss in spine surgery [WMD = ?467.49, 95% CI (685.47 to ?249.51); p < 0.05; I ² = 91%]. Compared with standard electrocautery, bipolar sealer was associated with lower rates of need for transfusion [OR = 0.30, 95% CI (0.16–0.55), p < 0.05; I ² = 0%]. In addition, patients in the BS group were likely to receive less amount of blood transfusion compared with patients in the control group[WMD = ?0.73, 95% CI (?1.37 to ?0.09), p < 0.05; I ² = 76%]. The mean operative time was shorter in the BS groups compared with the control group [SMD = ?0.36, 95% CI (?0.60 to ?0.13), p < 0.05; I ² = 0%]. There was no significant difference in terms of length of hospital stay [WMD = ?0.73, 95% CI (?1.96 to 0.51), p = 0.25; I ² = 67%] and postoperative wound infection [OR = 0.88, 95% CI (0.31–2.48), p = 0.81; I ² = 0.0%] between both groups.

Conclusions

The available evidence suggests that bipolar sealer is superior to standard electrocautery with less blood loss, shorter operation time and less transfusion requirement. There is no significant difference between both groups regarding length of hospitalization and wound infection. Hence, bipolar sealer is recommended in spine surgery. Because of the limitation of our study, more well-designed RCTs with large sample are required to provide further evidence of safety and efficacy between bipolar sealer and standard electrocautery in the treatment of spinal disease.

     

The distribution of infection with <Emphasis Type="Italic">Propionibacterium acnes</Emphasis> is equal in patients with cervical and lumbar disc herniation

Background

Cervical and back pains are important clinical problems affecting human populations globally. It is suggested that Propionibacterium acnes (P. acnes) is associated with disc herniation. The aim of this study is to evaluate the distribution of P. acnes infection in the cervical and lumbar disc material obtained from patients with disc herniation.

Methods and material

A total of 145 patients with mean age of 45.21 ± 11.24 years who underwent micro-discectomy in cervical and lumbar regions were enrolled into the study. The samples were excited during the operation and then cultured in the anaerobic incubations. The cultured P. acnes were detected by 16S rRNA-based polymerase chain reaction.

Results

In this study, 145 patients including 25 cases with cervical and 120 cases with lumbar disc herniation were enrolled to the study. There was no significant difference in the age of male and female patients (p = 0.123). P. acnes infection was detected in nine patients (36%) with cervical disc herniation and 46 patients (38.3%) with lumbar disc herniation and no significant differences were reported in P. acnes presence according to the disc regions (p = 0.508.). Moreover, there was a significant difference in the presence of P. acnes infection according to the level of lumbar disc herniation (p = 0.028).

Conclusion

According to the results, the presence of P. acnes is equal in patients with cervical and lumbar disc herniation. There was a significant difference in the distribution of P. acnes infection according to level of lumbar disc herniation.

Level of Evidence

II

     

Effect of laser and LED phototherapies on the healing of cutaneous wound on healthy and iron-deficient Wistar rats and their impact on fibroblastic activity during wound healing

Iron deficiency impairs the formation of hemoglobin, red blood cells, as well the transport of oxygen. The wound healing process involves numerous functions, many of which are dependent on the presence of oxygen. Laser has been shown to improve angiogenesis, increases blood supply, cell proliferation and function. We aimed to study the effect of λ660 nm laser and λ700 nm light-emitting diode (LED) on fibroblastic proliferation on cutaneous wounds on iron-deficient rodents. Induction of iron anemia was carried out by feeding 105 newborn rats with a special iron-free diet. A 1?×?1 cm wound was created on the dorsum of each animal that were randomly distributed into seven groups: I, control anemic; II, anemic no treatment; III, anemic?+?L; IV, anemic?+?LED; V, healthy no treatment; VI, healthy?+?laser; VII, healthy?+?LED (n?=?15 each). Phototherapy was carried out using either a diode laser (λ660 nm, 40 mW, 10 J/cm²) or a prototype LED device (λ700?±?20 nm, 15 mW, 10 J/cm²). Treatment started immediately after surgery and was repeated at 48-h interval during 7, 14, and 21 days. After animal death, specimens were taken, routinely processed, cut, stained with hematoxylin-eosin, and underwent histological analysis and fibroblast counting. Significant difference between healthy and anemic subjects on regards the number of fibroblast between treatments was seen (p?<?0.008, p?<?0.001). On healthy animals, significant higher count was seen when laser was used (p?<?0.008). Anemic subjects irradiated with LED showed significantly higher count (p?<?0.001). It is concluded that the use of LED light caused a significant positive biomodulation of fibroblastic proliferation on anemic animals and laser was more effective on increasing proliferation on non-anemics.     

Influence of sucrose on growth and sensitivity of <Emphasis Type="Italic">Candida albicans</Emphasis> alone and in combination with <Emphasis Type="Italic">Enterococcus faecalis</Emphasis> and <Emphasis Type="Italic">Streptococcus mutans</Emphasis> to photodynamic therapy

This study has evaluated the effects of photodynamic inactivation (PDI) using erythrosine as photosensitizer and green light-emitting diode (LED) on biofilms of Candida albicans alone and in combination with Enterococcus faecalis and Streptococcus mutans. We have also evaluated the effect of sucrose on biofilm formation and bacterial growth and sensitivity to PDI. Biofilms were formed in suspension of 10⁶ cells/ml on plates before being grown in broth culture with and without sucrose and incubated for 48 h. Next, the treatment was applied using erythrosine at a concentration of 400 μM for 5 min and green LED (532 ± 10 nm) for 3 min on biofilms alone and in combination. The plates were washed and sonicated to disperse the biofilms, and serial dilutions were carried and aliquots seeded in Sabouraud agar before incubation for 48 h. Next, the colony-forming units per milliliter (CFU/ml; log₁₀) were counted and analyzed statistically (ANOVA, Tukey test, P ≤ 0.05). Results show that S. mutans favors the growth of C. albicans in biofilms with sucrose, with treatment not being effective. However, when the biofilm was grown without sucrose, we found a reduction in biofilm formation and a significant decrease in the PDI treatment (P < 0.0001). In conclusion, both growth and sensitivity to PDI in biofilms of C. albicans are strongly influenced by bacterial combination, and the presence of sucrose affected directly the growth and sensitivity of the biofilm to PDI as sucrose is the substrate for construction of the exopolysaccharide matrix.     

Incisional Hernia Rates After Laparoscopic or Open Abdominal Surgery—A Systematic Review and Meta-Analysis

Background

Incisional hernias are one of the most common long-term complications associated with open abdominal surgery. The aim of this review and meta-analysis was to systematically assess laparoscopic versus open abdominal surgery as a general surgical strategy in all available indications in terms of incisional hernia occurrence.

Methods

A systematic literature search was performed to identify randomized controlled trials comparing incisional hernia rates after laparoscopic versus open abdominal surgery in all indications. Random effects meta-analyses were calculated and presented as risk differences (RD) with their corresponding 95 % confidence intervals (CI).

Results

24 trials (3490 patients) were included. Incisional hernias were significantly reduced in the laparoscopic group (RD ?0.06, 95 % CI [?0.09, ?0.03], p = 0.0002, I ² = 75). The advantage of the laparoscopic procedure persisted in the subgroup of total-laparoscopic interventions (RD ?0.14, 95 % CI [?0.22, ?0.06], p = 0.001, I ² = 87 %), whereas laparoscopically assisted procedures did not show a significant reduction of incisional hernias compared to open surgery (RD ?0.01, 95 % CI [?0.03, 0.01], p = 0.31, I ² = 35 %). Wound infections were significantly reduced in the laparoscopic group (RD ?0.06, 95 % CI [?0.09, ?0.03], p < 0.0001, I ² = 35 %); overall postoperative morbidity was comparable in both groups (RD ?0.06, 95 % CI [?0.13, 0.00], p = 0.06; I ² = 64 %). Open abdominal surgery showed a significantly longer hospital stay compared to laparoscopy (RD ?1.92, 95 % CI [?2.67, ?1.17], p < 0.00001, I ² = 87 %). At short-term follow-up, quality of life was in favor of laparoscopy.

Conclusions

Incisional hernias are less frequent using the total-laparoscopic approach instead of open abdominal surgery. Whenever possible, the less traumatic access should be chosen.

     

BRAF<Superscript>V600E</Superscript> Mutation is Associated with Decreased Disease-Free Survival in Papillary Thyroid Cancer

Background

The BRAF ^V600E mutation is a recognised molecular marker in papillary thyroid cancer (PTC), reported incidence from 30 to 80 %. BRAF^V600E aberrantly activates the MAPK pathway, a central regulator of cell growth and proliferation. Previous studies have reported conflicting data regarding the impact of BRAF^V600E on clinicopathological features of PTC. The study aims to determine whether BRAF^V600E is useful as a prognostic biomarker in PTC.

Methods

A cohort study of patients undergoing surgery for PTC was undertaken. The primary outcome measure was disease-free survival. Secondary outcome measures were tumour size, nodal positivity and radioactive iodine ablation rate. All cases were re-examined to confirm PTC. Immunohistochemistry for BRAF^V600E was performed on tissue microarrays. A single endocrine pathologist, blinded to clinicopathological data, interpreted staining.

Results

496 patients with PTC were included, and 309 (62 %) were BRAF^V600E positive. Tumour size was similar for BRAF^V600E-positive and -negative tumours (21.3 vs. 23.2 mm, p = 0.23). BRAF^V600E-positive patients were significantly older at first operation (mean age 45 versus 49 years, p = 0.003). BRAF^V600E-positive PTCs had a higher rate of disease recurrence (12.9 vs. 5.6 %, p = 0.004), lymph node metastasis (44 vs. 29.4 %, p = 0.004) and extra-thyroidal extension (44 vs. 22 %, p < 0.001). Five-year disease-free survival was 89.6 % for BRAF^V600E positive and 96.3 % for negative tumours, p < 0.001. There was no difference between groups for vascular invasion or multifocality. The mean follow-up was 57 months for both groups.

Conclusion

BRAF^V600E in PTC predicts an increased risk of lymph node metastasis, extra-thyroidal extension and reduced disease-free survival. It is an additional useful prognostic biomarker.

     

Lymph Node Status in Breast Cancer Does Not Predict Tumor Biology

Background/Objective

The 21-gene Oncotype DX^® Breast Recurrence Score^® (RS) assay has been prospectively validated as prognostic and predictive in node-negative, estrogen receptor-positive (ER+)/HER2? breast cancer patients. Less is known about its prognostic role in node-positive breast cancer. We compared RS results among patients with lymph node-negative (N0), micrometastatic (N1mi), and macrometastatic (N+) breast cancer to determine if nodal metastases are associated with more aggressive biology, as determined by RS.

Methods

Overall, 610,350 tumor specimens examined by the Genomic Health laboratory from February 2004 to August 2017 were studied. Histology was classified centrally, while lymph node status was determined locally. RS distribution (low: <?18; intermediate: 18–30; high: ≥?31) was compared by nodal status.

Results

Eighty percent (n = 486,013) of patients were N0, 4% (n = 24,325) were N1mi, 9% (n = 56,100) were N+, and 7% (n = 43,912) had unknown nodal status. Mean RS result was 18, 16.7, 17.3 and 18.9 in the N0, N1mi, N+, and unknown groups, respectively. An RS?≥?31 was seen in 10% of N0 patients, 7% of N1mi patients, and 8.0% of N+ patients. The likelihood of an RS ≥ 31 in N1mi and N+ patients varied with tumor histology, with only 2% of patients with classic infiltrating lobular cancer having an RS?≥?31, versus 7–9% of those with ductal carcinoma.

Conclusions

RS distribution among N0, N1mi, and N+ patients is similar, suggesting a spectrum of biology and potential chemotherapy benefit exists among node-negative and node-positive ER+/HER2? breast cancer patients. If RxPONDER does not show a chemotherapy benefit in N+ patients with a low RS result, our findings indicate that substantial numbers of patients could be spared the burden of chemotherapy.

     

In vitro comparison of an Er:YAG laser-activated bleaching system with different light-activated bleaching systems for color change,surface roughness,and enamel bond strength

To compare an Er:YAG laser-activated bleaching system with different light-activated in-office bleaching systems for color change, surface roughness, and post-bleaching enamel bond strength. 51 enamel slabs were prepared from the sound buccal enamel of extracted bovine teeth. The teeth were randomly divided into three groups according to different light-activated office bleaching systems (n?=?17): diode laser (Epic, Biolase) (940 nm, 7 W, continuous mode), Er:YAG laser (LightWalker, Fotona) (2940 nm, 50 mJ, 10 Hz, 1000 μs), and LED (Radii Plus) (440–480 nm, 1500 mW/cm²). All systems were used with their compatible bleaching agents according to manufacturers’ recommendations. The tooth color and surface roughness (Ra) were assessed at baseline and after bleaching using a spectrophotometer and a surface profilometer, respectively. The color change was determined by the CIE L*a*b* system (ΔE, ΔL*, Δa*, Δb*). Kruskal-Wallis test was used for color change whereas Kruskal-Wallis and Wilcoxon tests were used to analyze the roughness data. For shear bond strength test (SBS), composite cylinders were bonded on bleached enamel samples 14 days after bleaching procedures and stored in water (37 °C). Specimens were then debonded with a universal testing machine at 1 mm/min and data were analyzed by using Kruskal-Wallis test. All the tested bleaching systems were effective on color change (ΔE?>?3.3) and produced similar color change (p?>?0.05). There were no significant differences among the Ra values of the groups neither at baseline nor after bleaching (p?>?0.05). However, comparing the baseline and after bleaching Ra values, a significant increase was observed for all tested groups (p?<?0.05). Significant differences were also found among all systems for SBS (p?<?0.05). The highest values were obtained in Er:YAG group, whereas the LED group revealed the lowest values (p?<?0.05). All tested bleaching systems were effective on tooth whitening, whereas they all led to an increase on surface roughness. Although the current Er:YAG laser-activated bleaching system did not differ from other tested bleaching systems according to color change and surface roughness, it appears to provide better results in terms of SBS.     

Whole-body electromyostimulation to fight sarcopenic obesity in community-dwelling older women at risk. Resultsof the randomized controlled FORMOsA-sarcopenic obesity study

Summary

The effect of whole body-electromyostimulation in community-dwelling women ≥70 with sarcopenic obesity was heterogeneous, with high effects on muscle mass, moderate effects on functional parameters, and minor effects on fat mass. Further, we failed to determine a supportive effect of additional protein-enriched dietary supplementation in this albeit predominately well-nourished group.

Introduction

The aim of the study was to determine the effect of whole-body electromyostimulation (WB-EMS) on sarcopenic obesity (SO) in community-dwelling women more than 70 years with sarcopenic obesity.

Methods

Seventy-five community-dwelling women ≥70 years with SO were randomly allocated to either a WB-EMS-application with (WB-EMS &P; 24.9?±?1.9 kg/m²) or without (WB-EMS; 25.2?±?1.8 kg/m²) dietary supplementation (150 kcal/day, 56 % protein) or a non-training control group (CG; 24.7?±?1.4 kg/m²). WB-EMS consisted of one weekly session of 20 min (85 Hz, 350 μs, 4 s of strain–4 s of rest) performed with moderate to high intensity. Primary study endpoint was the Sarcopenia Z-Score constituted by skeletal muscle mass index (SMI, as assessed by dual energy X-ray absorptiometry), grip strength, and gait speed, and secondary study endpoint was body fat (%).

Results

Sarcopenia Z-score comparably increases in the WB-EMS and the WB-EMS&P-group (p?≤?.046). Both groups differ significantly (p?≤?.001) from the CG which deteriorated significantly (p?=?.006). Although body fat changes were most pronounced in the WB-EMS (?0.9?±?2.1; p?=?.125) and WB-EMS&P (?1.4?±?2.5; p?=?.028), reductions did not statistically differ (p?=?.746) from the CG (?0.8?±?2.7; p?=?.179). Looking behind the covariates, the most prominent changes were determined for SMI, with a significant increase in both EMS-groups (2.0–2.5 %; p?≤?.003) and a decrease in the CG (?1.2?±?3.1 %; p?=?.050) with significant between-group differences (p?=?.001).

Conclusion

WB-EMS is a safe and attractive method for increasing muscle mass and functional capacity in this cohort of women 70+ with SO; however, the effect on body fat is minor. Protein-enriched supplements did not increase effects of WB-EMS alone.

     

The effect of onabotulinumtoxinA according to site of injection in patients with overactive bladder: a systematic review and meta-analysis

Purpose

This study assessed the efficacy and safety of onabotulinumtoxinA according to injection site for treatment of overactive bladder.

Methods

A systematic literature review located randomized controlled trials of onabotulinumtoxinA treatment for neurogenic detrusor overactive bladder and idiopathic overactive bladder in adults. We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register using the Ovid platform. Meta-analysis was based on Cochrane Review Methods.

Results

Eight studies (419 participants) were included. Trigone-including injection demonstrated a significant improvement in symptom score (SMD = ? 0.53, 95% CI ? 1.04 to ? 0.02, P = 0.04, I ² = 78%), higher complete dryness rates (OR = 2.19 patients, 95% CI 1.32–3.63, P = 0.002, I ² = 41%), and lower frequency of incontinence episodes (WMD = ? 0.85 per day, 95% CI ? 1.55 to ? 0.16, P = 0.02, I ² = 87%) in patients. Comparing trigone-including injection to trigone-sparing injection, lower detrusor pressure (WMD = ? 2.55 cm H₂O, 95% CI ? 4.16 to ? 0.95, P = 0.002, I ² = 0%) and higher volume at first desire to void (WMD = 17.54 ml, 95% CI 1.00–34.07, P = 0.04, I ² = 0%) were observed with trigone-including injection. Between intradetrusor and suburothelial injection sites, there were no differences in efficacy or safety regarding the incidence of vesicoureteral reflux, hematuria, general weakness, bladder discomfort, large post-void residual, and urinary tract infection.

Conclusion

Trigone-including onabotulinumtoxinA injection has superior efficacy to trigone-sparing injection without increased complications. The depth of injection does not influence the efficacy or safety of onabotulinumtoxinA.

     

FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes

Background

This study aims to quantify changes in fibroblast growth factor 19 (FGF19) and bile acids (BAs) in patients with uncontrolled type 2 diabetes randomized to Roux-en-Y gastric bypass (RYGB) vs intensive medical management (IMM) and matched for similar reduction in HbA1c after 1 year of treatment.

Methods

Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (n?=?15) or RYGB (n?=?15).

Results

Mean HbA1c decreased from 9.7 to 6.4 % after RYGB and from 9.1 to 6.1 % in the IMM group. At 12 months, the number of diabetes medications used per subject in the RYGB group (2.5?±?0.5) was less than in the IMM group (4.6?±?0.3). After RYGB, FGF19 increased in the fasted (93?±?15 to 152?±?19 pg/ml; P?=?0.008) and postprandial states (area under the curve (AUC), 10.8?±?1.9 to 23.4?±?4.1 pg?×?h/ml?×?10³; P?=?0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC ×10³, 6.63?±?1.3 to 15.16?±?2.56 μM?×?h; P?=?0.003) and decreased after IMM (AUC ×10³, 8.22?±?1.24 to 5.70?±?0.70; P?=?0.01). No changes were observed in the ratio of 12α-hydroxylated/non-12α-hyroxylated BAs. Following RYGB, FGF19 AUC correlated with BAs (r?=?0.54, P?=?0.04) and trended negatively with HbA1c (r?=??0.44; P?=?0.09); these associations were not observed after IMM.

Conclusions

BA and FGF19 levels increased after RYGB but not after IMM in subjects who achieved similar improvement in glycemic control. Further studies are necessary to determine whether these hormonal changes facilitate improved glucose homeostasis.

     

Influence of Age on the Clinical Outcome of Breast Cancer for Men and the Development of Second Primary Cancers

Background

Low incidence of breast cancer in men (BCM) (<?1% of all breast cancers) has led to a paucity of outcome data. This study evaluated the impact of age on BCM outcomes.

Methods

For this study, BCM patients treated between 2000 and 2011 were stratified by age (≤?65 or?>?65 years). Kaplan–Meier methods were used to compare overall survival (OS) and breast cancer-specific survival (BCSS). Competing-risk methods analyzed time to second primary cancers (SPCs), with any-cause death treated as a competing risk.

Results

The study identified 152 BCM patients with a median age of 64 years (range 19–96 years). The median body mass index (BMI) was 28 kg/m². Men age 65 years or younger (n?=?78, 51%) were more overweight/obese than men older than 65 years (n?=?74, 49%) (89% vs 74%, respectively; P?=?0.008). Both groups had similar nodal metastases rates (P?=?0.4), estrogen receptor positivity (P?=?1), and human epidermal growth factor receptor 2 (HER2)neu overexpression (P?=?0.6). Men 65 years of age or younger were more likely to receive chemotherapy (P?=?0.002). The median follow-up period was 5.8 years (range 0.1–14.4 years). The 5-year OS was 86% (95% confidence interval [CI] 80–93%), whereas the 5-year BCSS was 95% (95% CI 91–99%). The BCM patients 65 years of age and younger had better OS (P?=?0.003) but not BCSS (P?=?0.8). The 5-year cumulative incidence of SPC was 8.4% (95% CI 3.4–13.4%). The prior SPC rate was higher for men older than 65 years (n?=?20, 31%) than for those age 65 years or younger (n?=?7, 11%) (P?=?0.008). This did not account for differences in life years at risk. No difference was observed in SPC cumulative incidence stratified by age (P?=?0.3).

Conclusions

Men 65 years of age or younger received more chemotherapy and had improved OS, but not BCSS, compared with men older than 65 years. For all BCM, SPC is a risk, and appropriate screening may be warranted.