The Single-Incision Power Optimizing Cost-Effective Repair (SPOC) method reattaches the distal biceps tendon to its original posterior anatomic footprint and utilizes the anterior cortex of the ...supinated radius for fixation. The purpose of the study was to define the long-term complications and durability of the SPOC method.
Two hundred and eighteen patients underwent the SPOC repair of distal biceps ruptures from 2008 to 2020, with 185 having at least 1-year follow-up data. The average follow-up was 50.1 months. Information regarding smoking, body mass index, interval between injury and surgery, peripheral nerve injury, heterotopic ossification, vascular injury, re-rupture, chronic regional pain syndrome, fracture of the radius, loss of motion, pain with use, and deformity were acquired.
No complication occurred beyond the third postoperative month. No patient complained of severe lateral antebrachial cutaneous nerve-related symptoms. Major complications exclusive of re-rupture occurred include 1 case of heterotopic ossification and 1 deep infection. Major complications with re-ruptures occurred in 9 patients (4.8%). Seven of the re-ruptures (78%) were associated with an unexpected forceful contraction within the first 4 weeks postop. All complications aside from 1 minor complication occurred in the chronic group. Long term follow-up revealed no re-ruptures and high satisfaction rate with return of strength, motion, and biceps profile.
The safety profile of the SPOC repair is consistent with those of other published repairs. Major complications were associated with prolonged intervals between injury and reconstruction. Re-ruptures were associated with worker’s compensation status and patient noncompliance with postoperative protocols.
Photoreactions of 4-nitroanisole and the 2-halo-4-nitroanisoles (halogen = F, Cl, Br, and I) with the nucleophiles hydroxide ion and pyridine have been investigated quantitatively to extend the ...findings recently communicated for cyanide ion. The halonitroanisoles on excitation form triplet π,π* states, which undergo substitution of the halogen by nucleophiles. Chemical yields of photoproducts, Stern−Volmer kinetic plots, triplet lifetimes, and triplet yields are reported for the five compounds with the three nucleophiles. Following a standard kinetic treatment, 73 rate constants are determined for elementary reactions of the triplets including quenching and various nucleophilic addition processes. The photoadditions are roughly 14 orders of magnitude faster than thermal counterparts. Rate constants for attack at the fluorine-bearing carbon of triplet 2-fluoro-4-nitroanisole are 2.9 × 109, 1.3 × 109, and 6.3 × 108 M-1 s-1 for cyanide ion, hydroxide ion, and pyridine, respectively. The relative rates for attack at the halogen-bearing carbons for F/Cl/Br/I are 27:1.9:1.9:1 (cyanide ion), 29:2.6:2.4:1 (hydroxide ion), and 39:3.9:3.5:1 (pyridine), respectively. The relative nucleophilicities vary somewhat with the attack site; they are about 5:2:1 for cyanide ion, hydroxide ion, and pyridine for attack at the halogen-bearing carbons. The trend of the element effect opposes that of aliphatic substitution and elimination but is similar in size and parallel to that of thermal nucleophilic aromatic substitution. Relative nucleophilicities in the photoreactions are also similar to those of comparable but vastly slower thermal reactions. The findings imply that the efficiency-determining step of the halogen photosubstitution is simple formation of a σ-complex through electron-paired bonding within the triplet manifold.
Johnsona and DeCosse describe two patients in whom colonoscopy illuminated a long history of appendicitis and could have led to an earlier diagnosis. One case report where colonoscopy was used to ...diagnose acute appendicitis is examined.
Mycorrhizal symbioses link the biosphere with the lithosphere by mediating nutrient cycles and energy flow though terrestrial ecosystems. A more mechanistic understanding of these plant–fungal ...associations may help ameliorate anthropogenic changes to C and N cycles and biotic communities. We explore three interacting principles: (1) optimal allocation, (2) biotic context and (3) fungal adaptability that may help predict mycorrhizal responses to carbon dioxide enrichment, nitrogen eutrophication, invasive species and land‐use changes. Plant–microbial feedbacks and thresholds are discussed in light of these principles with the goal of generating testable hypotheses. Ideas to develop large‐scale collaborative research efforts are presented. It is our hope that mycorrhizal symbioses can be effectively integrated into global change models and eventually their ecology will be understood well enough so that they can be managed to help offset some of the detrimental effects of anthropogenic environmental change.
Pulmonary fibrosis is a progressive inflammatory disease with high mortality and limited therapeutic options. Previous genetic and immunologic investigations suggest common intersections between ...idiopathic pulmonary fibrosis (IPF), sarcoidosis, and murine models of pulmonary fibrosis. To identify immune responses that precede collagen deposition, we conducted molecular, immunohistochemical, and flow cytometric analysis of human and murine specimens. Immunohistochemistry revealed programmed cell death-1 (PD-1) up-regulation on IPF lymphocytes. PD-1
CD4
T cells with reduced proliferative capacity and increased transforming growth factor-β (TGF-β)/interleukin-17A (IL-17A) expression were detected in IPF, sarcoidosis, and bleomycin CD4
T cells. PD-1
T helper 17 cells are the predominant CD4
T cell subset expressing TGF-β. Coculture of PD-1
CD4
T cells with human lung fibroblasts induced collagen-1 production. Strikingly, ex vivo PD-1 pathway blockade resulted in reductions in TGF-β and IL-17A expression from CD4
T cells, with concomitant declines in collagen-1 production from fibroblasts. Molecular analysis demonstrated PD-1 regulation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Chemical blockade of STAT3, using the inhibitor STATTIC, inhibited collagen-1 production. Both bleomycin administration to PD-1 null mice or use of antibody against programmed cell death ligand 1 (PD-L1) demonstrated significantly reduced fibrosis compared to controls. This work identifies a critical, previously unrecognized role for PD-1
CD4
T cells in pulmonary fibrosis, supporting the use of readily available therapeutics that directly address interstitial lung disease pathophysiology.
Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organ systems, including the lungs. Interstitial lung disease (ILD) is the leading cause of death in SSc.There are no ...valid biomarkers to predict the occurrence of SSc-ILD, although auto-antibodies against anti-topoisomerase I and several inflammatory markers are candidate biomarkers that need further evaluation. Chest auscultation, presence of shortness of breath and pulmonary function testing are important diagnostic tools, but lack sensitivity to detect early ILD. Baseline screening with high-resolution computed tomography (HRCT) is therefore necessary to confirm an SSc-ILD diagnosis. Once diagnosed with SSc-ILD, patients' clinical courses are variable and difficult to predict, although certain patient characteristics and biomarkers are associated with disease progression. It is important to monitor patients with SSc-ILD for signs of disease progression, although there is no consensus about which diagnostic tools to use or how often monitoring should occur. In this article, we review methods used to define and predict disease progression in SSc-ILD.There is no valid definition of SSc-ILD disease progression, but we suggest that either a decline in forced vital capacity (FVC) from baseline of ≥10%, or a decline in FVC of 5-9% in association with a decline in diffusing capacity of the lung for carbon monoxide of ≥15% represents progression. An increase in the radiographic extent of ILD on HRCT imaging would also signify progression. A time period of 1-2 years is generally used for this definition, but a decline over a longer time period may also reflect clinically relevant disease progression.
Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), ...mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity.
In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (
= 15) or saline (
= 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were
) body weight,
) fructosamine levels,
) glucose and insulin during a mixed meal test (MMT),
) energy expenditure (EE),
) energy intake (EI), and
) mean glucose and measures of glucose variability during continuous glucose monitoring.
GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (
= 0.025) with GOP (mean change -4.4 95% CI -5.3, -3.5 kg) versus saline (-2.5 -4.1, -0.9 kg). GOP led to a greater improvement (
= 0.0026) in fructosamine (-44.1 -62.7, -25.5 µmol/L) versus saline (-11.7 -18.9, -4.5 µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD.
GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.
This randomized trial comparing retropubic and transobturator slings for the treatment of stress urinary incontinence showed equivalent rates of treatment success according to objective criteria; the ...rates of treatment success in the two groups according to subjective criteria were similar but did not meet the criteria for equivalence. Complications differed in the two groups, with more voiding dysfunction requiring surgery in the retropubic-sling group and more neurologic symptoms in the transobturator-sling group.
In this randomized trial, two surgical approaches for the treatment of stress urinary incontinence had similar cure rates, although the complications differed by group.
Urinary incontinence affects up to 50% of women, resulting in substantial medical, social, and economic burdens.
1
,
2
Among U.S. women with urinary incontinence, 15 to 80% have a component of stress incontinence,
3
which results in leakage of urine during physical exertion, sneezing, and coughing.
4
Of these women, 4 to 10% undergo surgery.
5
In 1996, Ulmsten et al.
6
introduced a procedure that involved the placement of a retropubic midurethral mesh sling for the treatment of stress incontinence; this procedure was less invasive than the Burch colposuspension and the autologous rectus fascial sling procedures that were the reference standards at the time. . . .
Lack of sufficient efficacy is the most common cause of attrition in late-phase drug development. It has long been envisioned that genetics could drive stratified drug development by identifying ...those patient subgroups that are most likely to respond. However, this vision has not been realized as only a small proportion of drugs have been found to have germline genetic predictors of efficacy with clinically meaningful effects, and so far all but one were found after drug approval. With the exception of oncology, systematic application of efficacy pharmacogenetics has not been integrated into drug discovery and development across the industry. Here, we argue for routine, early and cumulative screening for genetic predictors of efficacy, as an integrated component of clinical trial analysis. Such a strategy would identify clinically relevant predictors that may exist at the earliest possible opportunity, allow these predictors to be integrated into subsequent clinical development and provide mechanistic insights into drug disposition and patient-specific factors that influence response, therefore paving the way towards more personalized medicine.
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