Closure of the primary opening of a fistula tract using a suturable biologic anal fistula plug is an effective method of treating anorectal fistulas. The method seems to be more reliable than fibrin glue closure. The greater efficacy of the fistula plug may be the result of the ability to suture the plug in the primary opening, therefore, closing the primary opening more effectively. Further prospective, long-term studies are warranted.
Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.
Despite advances in neoadjuvant and adjuvant therapy, attention to proper surgical technique, and improved pathological staging for both the primary and metastatic lesions, almost half of all colorectal cancer patients will develop recurrent disease. More concerning, this includes ~25% of patients with theoretically curable node-negative, non-metastatic Stage I and II disease. Given the annual incidence of colorectal cancer, approximately 150,000 new patients are candidates each year for follow-up surveillance. When combined with the greater population already enrolled in a surveillance protocol, this translates to a tremendous number of patients at risk for recurrence. It is therefore imperative that strategies aim for detection of recurrence as early as possible to allow initiation of treatment that may still result in cure. Yet, controversy exists regarding the optimal surveillance strategy (high-intensity vs. traditional), ideal testing regimen, and overall effectiveness. While benefits may involve earlier detection of recurrence, psychological welfare improvement, and greater overall survival, this must be weighed against the potential disadvantages including more invasive tests, higher rates of reoperation, and increased costs. In this review, we will examine the current options available and challenges surrounding colorectal cancer surveillance and early detection of recurrence.
Background
The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancers.
Objective
Examine the association between screening colonoscopy and incident late-stage colorectal cancer (CRC) risk.
Design
Nested case-control study.
Setting
Four U.S. health plans
Patients
Average-risk adults with ≥5 years of enrollment in one of the health plans (n=1,039). Cases were 55–85 years old on their diagnosis date (reference date) of stage ≥IIB (late-stage) CRC during 2006–2008. We selected 1–2 controls for each case, matched on birth year, gender, health plan, and prior enrollment duration.
Measurements
Receipt of CRC screening between 3 months and up to 10 years before the reference date, ascertained through medical record audits. We compared cases and controls on receipt of screening colonoscopy or sigmoidoscopy using conditional logistic regressions that accounted for health history, socioeconomic status and other screening exposures.
Results
In analyses restricted to 471 eligible cases and their matched controls (n=509), 13 cases (2.8%) and 46 controls (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.30 (95% confidence interval [CI]: 0.15–0.59) for any late-stage CRC, 0.37 (CI: 0.16–0.82) for right colon cancers, and 0.26 (CI: 0.06–1.11) for left-sided colon/rectum cancers. Ninety-two cases (19.5%) and 173 controls (34.0%) underwent screening sigmoidoscopy, corresponding to an AOR of 0.51 (CI: 0.36–0.71) overall, 0.80 (CI: 0.52–1.25) for right colon late-stage cancers, and 0.26 (CI: 0.14–0.49) for left colon/rectum cancers.
Limitations
The small number of screening colonoscopies affected the precision of our estimates.
Conclusions
Screening with colonoscopy in average-risk persons was associated with reduced risk of diagnosis with incident late-stage CRC in both the right colon and left colon/rectum. For sigmoidoscopy, this association was observed for left-sided CRC, but the association for right colon late-stage cancer was not statistically significant.
Primary Funding Source
National Cancer Institute of the National Institutes of Health.
Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle dysfunction leading to premature death by the third decade of life. The mdx mouse, the most widely used animal model of DMD, has been extremely useful to study disease mechanisms and to screen new therapeutics. However, unlike patients with DMD, mdx mice have a very mild motor function deficit, posing significant limitations for its use as a platform to assess the impact of treatments on motor function. It has been suggested that an mdx variant, the mdx(5cv) mouse, might be more severely affected. Here, we compared the motor activity, histopathology, and individual muscle force measurements of mdx and mdx(⁵cv) mice. Our study revealed that mdx(⁵cv) mice showed more severe exercise-induced fatigue, Rotarod performance deficits, and gait anomalies than mdx mice and that these deficits began at a younger age. Muscle force studies showed more severe strength deficits in the diaphragm of mdx(⁵cv) mice compared to mdx mice, but similar force generation in the extensor digitorum longus. Muscle histology was similar between the two strains. Differences in genetic background (genetic modifiers) probably account for these functional differences between mdx strains. Overall, our findings indicate that the mdx and mdx(⁵cv) mouse models of DMD are not interchangeable and identify the mdx(⁵cv) mouse as a valuable platform for preclinical studies that require assessment of muscle function in live animals.
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