Elbow Ulnar Collateral Ligament Reconstruction Using the Novel Docking Plus Technique in 324 Athletes

BACKGROUND: This retrospective case series examined 324 athletes who received elbow ulnar collateral ligament (UCL) reconstruction by a single surgeon in a private practice over a 9-year period. The novel Docking Plus technique for elbow UCL reconstruction in 324 athletes provided good or excellent Conway score results in 88% of patients. The preponderance of previous studies examining UCL reconstruction outcomes were performed by surgeons at one of only three institutions (Andrews Institute, Hospital for Special Surgery, Kerlan Jobe Orthopedic Clinic). METHODS: Patients undergoing UCL reconstruction from November 2005 to December 2014 were identified and contacted with a mailed survey and phone call. These patients were given a subjective 19 question survey assessing their outcomes from surgery. RESULTS: The participants who responded to our survey were 90% male and 77% baseball players, 73% of which were pitchers. Of the baseball players who responded, 51.9% were in high school at the time of their surgery, 37% college, 6.5% minor leagues, and 2.2% in Major League Baseball. After surgery, 36% of survey responders returned to a higher level of competition than previously. For example, a high school athlete who had UCL reconstruction and went on to pitch in college. Further, 45% returned to the same level, and 7% returned to a lower level. Subjective satisfaction, was reported in 92% of responders and 97.2% reported that, having surgery was a good idea. Symptom onset in the responding athletes was 58.9% sudden, and 41.1% gradual. Overall, 90.9% of respondents returned to play in less than 1.5 years while 6.3% never were able to return. Re-tear occurred in 2.5% of patients, while 8.8% had subjective nerve dysfunction for at least 3 months following surgery. CONCLUSION: The Docking Plus technique can produce excellent subjective and objective results in athletes. Further study is warranted to see the effects of this procedure in other settings and determine which method of reconstruction or repair is superior

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

The genomics of heart failure: design and rationale of the HERMES consortium

Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.</p

The genomics of heart failure: design and rationale of the HERMES consortium

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome‐wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow‐up following heart failure diagnosis ranged from 2 to 116 months. Forty‐nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low‐frequency variants (allele frequency 0.01–0.05) at P &lt; 5 × 10−8 under an additive genetic model. Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction

Ultrafast Transient Absorption Studies on Photosystem I Reaction Centers from Chlamydomonas reinhardtii. 1. A New Interpretation of the Energy Trapping and Early Electron Transfer Steps in Photosystem I

The energy transfer and charge separation kinetics in core Photosystem I (PSI) particles of Chlamydomonas reinhardtii has been studied using ultrafast transient absorption in the femtosecond-to-nanosecond time range. Although the energy transfer processes in the antenna are found to be generally in good agreement with previous interpretations, we present evidence that the interpretation of the energy trapping and electron transfer processes in terms of both kinetics and mechanisms has to be revised substantially as compared to current interpretations in the literature. We resolved for the first time i), the transient difference spectrum for the excited reaction center state, and ii), the formation and decay of the primary radical pair and its intermediate spectrum directly from measurements on open PSI reaction centers. It is shown that the dominant energy trapping lifetime due to charge separation is only 6–9 ps, i.e., by a factor of 3 shorter than assumed so far. The spectrum of the first radical pair shows the expected strong bleaching band at 680 nm which decays again in the next electron transfer step. We show furthermore that the early electron transfer processes up to ∼100 ps are more complex than assumed so far. Several possibilities are discussed for the intermediate redox states and their sequence which involve oxidation of P700 in the first electron transfer step, as assumed so far, or only in the second electron transfer step, which would represent a fundamental change from the presently assumed mechanism. To explain the data we favor the inclusion of an additional redox state in the electron transfer scheme. Thus we distinguish three different redox intermediates on the timescale up to 100 ps. At this level no final conclusion as to the exact mechanism and the nature of the intermediates can be drawn, however. From comparison of our data with fluorescence kinetics in the literature we also propose a reversible first charge separation step which has been excluded so far for open PSI reaction centers. For the first time an ultrafast 150-fs equilibration process, occurring among exciton states in the reaction center proper, upon direct excitation of the reaction center at 700 nm, has been resolved. Taken together the data call for a fundamental revision of the present understanding of the energy trapping and early electron transfer kinetics in the PSI reaction center. Due to the fact that it shows the fastest trapping time observed so far of any intact PSI particle, the PSI core of C. reinhardtii seems to be best suited to further characterize the electron transfer steps and mechanisms in the reaction center of PSI

Ultrafast Transient Absorption Studies on Photosystem I Reaction Centers from Chlamydomonas reinhardtii. 2: Mutations near the P700 Reaction Center Chlorophylls Provide New Insight into the Nature of the Primary Electron Donor

The energy transfer and charge separation kinetics in several core Photosystem I particles of Chlamydomonas reinhardtii with point mutations around the P(A) and P(B) reaction center chlorophylls (Chls) have been studied using ultrafast transient absorption spectroscopy in the femtosecond to nanosecond time range to characterize the influence on the early electron transfer processes. The data have been analyzed in terms of kinetic compartment models. The adequate description of the transient absorption kinetics requires three different radical pairs in the time range up to ∼100 ps. Also a charge recombination process from the first radical pair back to the excited state is present in all the mutants, as already shown previously for the wild-type (Müller, M. G., J. Niklas, W. Lubitz, and A. R. Holzwarth. 2003. Biophys. J. 85:3899–3922; and Holzwarth, A. R., M. G. Müller, J. Niklas, and W. Lubitz. 2005. J. Phys. Chem. B. 109:5903–59115). In all mutants, the primary charge separation occurs with the same effective rate constant within the error limits as in the wild-type (»350 ns(−1)), which implies an intrinsic rate constant of charge separation of <1 ps(−1). The rate constant of the secondary electron transfer process is slowed down by a factor of ∼2 in the mutant B-H656C, which lacks the ligand to the central metal of Chl P(B). For the mutant A-T739V, which breaks the hydrogen bond to the keto carbonyl of Chl P(A), only a slight slowing down of the secondary electron transfer is observed. Finally for mutant A-W679A, which has the Trp near the P(A) Chl replaced, either no pronounced effect or, at best, a slight increase on the secondary electron transfer rate constants is observed. The effective charge recombination rate constant is modified in all mutants to some extent, with the strongest effect observed in mutant B-H656C. Our data strongly suggest that the Chls of the P(A) and P(B) pair, constituting what is traditionally called the “primary electron donor P700”, are not oxidized in the first electron transfer process, but rather only in the secondary electron transfer step. We thus propose a new electron transfer mechanism for Photosystem I where the accessory Chl(s) function as the primary electron donor(s) and the A(0) Chl(s) are the primary electron acceptor(s). This new mechanism also resolves in a straightforward manner the difficulty with the previous mechanism, where an electron would have to overcome a distance of ∼14 Å in <1 ps in a single step. If interpreted within a scheme of single-sided electron transfer, our data suggest that the B-branch is the active branch, although parallel A-branch activity cannot be excluded. All the mutations do affect to a varying extent the energy difference between the reaction center excited state RC* and the first radical pair and thus affect the rate constant of charge recombination. It is interesting to note that the new mechanism proposed is in fact analogous to the electron transfer mechanism in Photosystem II, where the accessory Chl also plays the role of the primary electron donor, rather than the special Chl pair P680 (Prokhorenko, V. and A. R. Holzwarth. 2000. J. Phys. Chem. B. 104:11563–11578)

Proximal humeral fracture-dislocations: which patterns can be reduced in the emergency department

BACKGROUND: Shoulder fracture-dislocations can represent a challenging management scenario in the emergency department (ED) because of concern for the presence of occult fractures that may displace during a reduction attempt. The alternative, a closed reduction attempt in the operating room, has the benefit of full paralysis but requires additional resource utilization. There is limited guidance in the literature about the risks of an initial reduction attempt in the ED as a function of fracture pattern to help guide physicians with this decision. METHODS: This was a retrospective case review of adult patients with shoulder dislocations and fracture-dislocations seen in the ED at a level 1 trauma center over a 10-year period. Imaging and medical records were reviewed to evaluate whether the reduction attempt was successful, unsuccessful without worsening, or unsuccessful with worsening alignment of any fractures, as well as the ultimate clinical outcome. RESULTS: We identified 165 patients with fracture-dislocations and 484 patients with simple dislocations during the same period. Of the patients with fracture-dislocations, 103 had greater tuberosity fractures, 12 had nondisplaced surgical neck fractures, and 50 had displaced surgical neck fractures. None of the patients with simple dislocations had displacement during an ED reduction attempt, including 100 patients aged \u3e 65 years. Of the 103 patients with greater tuberosity fracture-dislocations, only 1 had displacement of a humeral shaft fracture during ED reduction. Displacement occurred in 6 of 8 patients with nondisplaced neck fractures who underwent an initial ED reduction attempt vs. 1 of 4 patients who underwent the initial reduction attempt in the operating room. ED reduction was attempted in 25 of the 50 displaced humeral neck fracture-dislocations and was successful in 10 of these (40%). CONCLUSIONS: For patients with greater tuberosity fracture-dislocations, there is a low rate of displacement with a reduction attempt in the ED, but an ED reduction attempt in nondisplaced neck fractures is not recommended because of the high rate of displacement. For displaced neck fractures, closed reduction can be successful in select patients. Finally, these data confirm prior reports that closed reduction of simple shoulder dislocations in patients aged \u3e 65 years is safe in the ED

Elbow Ulnar Collateral Ligament Reconstruction Using a 4-Strand Docking Plus Technique

The “Docking Plus” technique for elbow ulnar collateral ligament (UCL) surgery is described in the following text and video. Depite the general success of UCL surgery, significant rates of retear and failure of return to competition persist. Hypothesized reasons for UCL surgery failure include insufficient graft strength (midsubstance tears), insufficient graft tensioning (functional UCL insufficiency, valgus extension overload), and insufficient healing of graft to bone (proximal avulsions). This technique is meant to incorporate the best aspects of the previously described techniques for UCL reconstruction to create a larger, stronger, better-tensioned graft with a larger healing surface area to bone, a lower retear rate, and a lower risk of complications. The Docking Plus technique has been used since 2012

A Biomechanical Cadaver Comparison of Suture Button Fixation to Plate Fixation for Pubic Symphysis Diastasis

Objectives: To determine whether suture button fixation of the pubic symphysis is biomechanically similar to plate fixation in the treatment of partially stable pelvic ring injuries. Methods: Twelve pelvis specimens were harvested from fresh frozen cadavers. Dual-x-ray-absorptiometry (DXA) scans were obtained for all specimens. The pubic symphysis of each specimen was sectioned to simulate a partially stable pelvic ring injury. Six of the pelvises were instrumented using a 6 hole, 3.5 mm low profile pelvis plate and six of the pelvises were instrumented with two suture button devices. Biomechanical testing was performed on a pneumatic testing apparatus in a manner that simulates vertical stance. Displacement measurements of the superior, middle, and inferior pubic symphysis were obtained prior to loading, after an initial 440 N load, and after 30,000 and 60,000 rounds of cyclic loading. Statistical analysis was performed using Wilcoxon-Mann-Whitney tests, Fisher\u27s exact test, and Cohen\u27s d to calculate effect size. Significance was set at p \u3c 0.05. Results: There was no difference between groups for DXA T scores (p = 0.749). Between group differences in clinical load to failure (p = 0.65) and ultimate load to failure (p = 0.52) were not statistically significant. For symphysis displacement, the change in fixation strength and displacement with progressive cyclic loading was not significant when comparing fixation types (superior: p = 0.174; middle: p = 0.382; inferior: p = 0.120). Conclusion: Suture button fixation of the pubic symphysis is biomechanically similar to plate fixation in the management of partially stable pelvic ring injuries

A Biomechanical Cadaver Comparison of Suture Button Fixation to Plate Fixation for Pubic Symphysis Diastasis

Objectives: To determine whether suture button fixation of the pubic symphysis is biomechanically similar to plate fixation in the treatment of partially stable pelvic ring injuries. Methods: Twelve pelvis specimens were harvested from fresh frozen cadavers. Dual-x-ray-absorptiometry (DXA) scans were obtained for all specimens. The pubic symphysis of each specimen was sectioned to simulate a partially stable pelvic ring injury. Six of the pelvises were instrumented using a 6 hole, 3.5 mm low profile pelvis plate and six of the pelvises were instrumented with two suture button devices. Biomechanical testing was performed on a pneumatic testing apparatus in a manner that simulates vertical stance. Displacement measurements of the superior, middle, and inferior pubic symphysis were obtained prior to loading, after an initial 440 N load, and after 30,000 and 60,000 rounds of cyclic loading. Statistical analysis was performed using Wilcoxon-Mann-Whitney tests, Fisher\u27s exact test, and Cohen\u27s d to calculate effect size. Significance was set at p \u3c 0.05. Results: There was no difference between groups for DXA T scores (p = 0.749). Between group differences in clinical load to failure (p = 0.65) and ultimate load to failure (p = 0.52) were not statistically significant. For symphysis displacement, the change in fixation strength and displacement with progressive cyclic loading was not significant when comparing fixation types (superior: p = 0.174; middle: p = 0.382; inferior: p = 0.120). Conclusion: Suture button fixation of the pubic symphysis is biomechanically similar to plate fixation in the management of partially stable pelvic ring injuries