Management of the Crura During Laparoscopic Sleeve Gastrectomy.

METHODS: This is a retrospective cohort study that evaluated patients undergoing LSG performed by a single surgeon in a 7-year period. Data were collected via chart review. The primary endpoint was hiatal hernia presence at 5 years post-operatively. Secondary endpoints included post-procedural complications (nausea, vomiting, dysphagia, or reflux) at 30 days post-operatively. RESULTS: A total of 361 patients were included in the analysis: 154 without crural closure, 164 primary crural closure, and 43 primary crural closure with mesh reinforcement. Rates of hiatal hernia occurrence at 5 years were 9.7% (no closure), 14.0% (primary closure), and 16.3% (closure with mesh reinforcement), respectively, and did not differ significantly among the 3 cohorts (P = .37). Overall rates of 30-day complications were 11.5%, 21.5%, and 28.6%, respectively (P = .015). CONCLUSION: Rates of hiatal hernia after sleeve gastrectomy do not differ, regardless of management of the crura. In addition, and perhaps more significantly, avoidance of crural closure was associated with fewer 30-day complications. In fact, the highest rate of 30-day complications was seen in the group that received closure with mesh reinforcement. These data suggest that crural closure during LSG should be avoided. Further prospective study of these findings is warranted.

Predicting Successful Laparoendoscopic Transhiatal Esophagectomy (THE) by Mediastinal Height Measurement.

BACKGROUND: Laparoendoscopic transhiatal esophagectomy (THE) provides advantages over traditional THE by not only avoiding laparotomy but by also allowing more precise esophageal mobilization. Occasionally, the length of the gastric conduit is insufficient to allow delivery into the neck after laparoscopic mobilization and requires laparotomy to complete the procedure. We hypothesize that the need for laparotomy will correlate with the measurement of mediastinal height (distance from thoracic vertebrae T1-T12) on chest CT. METHODS: Medical records of all patients who underwent attempted laparoendoscopic-assisted THE at a tertiary referral center between March 1, 2003 and January 31, 2019 were reviewed. Patients' mediastinal height was measured using computed tomography (CT) imaging of the chest by investigators and analyzed for correlation between mediastinal height and successful completion of a totally laparoendoscopic procedure. RESULTS: A total of 21 cases met inclusion criteria: 9 successful laparoendoscopic THE procedures and 12 failed laparoendoscopic THE procedures (those requiring addition of a mini-laparotomy or thoracotomy). The mean mediastinal length for successful laparoendoscopic surgery was 23.5 cm, whereas the mean mediastinal length for failed laparoscopic surgeries was 24.8 cm (P = .03). Patient's overall height was not found to correlate with the need for conversion. CONCLUSIONS: Shorter mediastinal length is associated with successful laparoendoscopic or laparoscopic THE. This information is readily available to clinicians from routine preoperative staging studies (chest CT) and may be used to potentially predict the success rate of a totally laparoendoscopic approach and aid in patient selection. Further prospective evaluation of these findings is warranted.

Certificates of Confidentiality: Protecting Human Subject Research Data in Law and Practice.

The federal Certificate of Confidentiality plays an important role in research on sensitive topics by authorizing researchers to refuse to disclose identifiable research data in response to subpoenas in any legal setting. However, there is little known about how effective Certificates are in practice. This article draws on our legal and empirical research on this topic to fill this information gap. It includes a description of the purpose of Certificates, their legislative and regulatory history, and a summary of the few reported and unreported cases that have dealt with Certificates. In addition, we outline other statutory confidentiality protections, compare them to the Certificate's protections, and analyze some of the vulnerabilities of a Certificate's protections. This analysis allows us to make specific recommendations for strengthening the protections afforded to research data.

Certificates of Confidentiality: Protecting Human Subject Research Data in Law and Practice.

Researchers often require and collect sensitive information about individuals to answer important scientific questions that impact individual health and well-being and the public health. Researchers recognize they have a duty to maintain the confidentiality of the data they collect and typically make promises, which are documented in the consent form. The legal interests of others, however, can threaten researchers' promises of confidentiality, if they seek access to the data through subpoena. Certificates of Confidentiality (Certificates), authorized by federal statute, are an important tool for protecting individually identifiable sensitive research data from compelled disclosure. However, questions persist in the research community about the strength of Certificate protections, and the evidence on which to judge the strength is scant. In this article, we address those questions through a careful examination of the legislation and regulations concerning Certificates and the reported and unreported cases we have identified through our legal research and interviews with legal counsel about their experiences with Certificates. We also analyze other statutes that protect research data to compare them to the Certificate's protections, and we review other legal strategies available for protecting research data. Based on our analysis, we conclude with recommendations for how to strengthen protection of sensitive research data.

In vivo biosynthesis of an Ala-scan library based on the cyclic peptide SFTI-1.

We present the in vivo biosynthesis of wild-type sunflower trypsin inhibitor 1 (SFTI-1) inside E. coli cells using an intramolecular native chemical ligation in combination with a modified protein splicing unit. SFTI-1 is a small backbone cyclized polypeptide with a single disulfide bridge. A small library containing multiple Ala mutants was also biosynthesized and its activity was assayed using a trypsin-binding assay. This study clearly demonstrates the exciting possibility of generating large cyclic peptide libraries in live E. coli cells, and is a critical first step for developing in vivo screening and directed evolution technologies using the cyclic peptide SFTI-1 as a molecular scaffold.

Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction.

Myocardial remodeling after myocardial infarction (MI) is associated with increased levels of the matrix metalloproteinases (MMPs). Levels of two MMP species, MMP-2 and MMP-9, are increased after MI, and transgenic deletion of these MMPs attenuates post-MI left ventricular (LV) remodeling. This study characterized the spatiotemporal patterns of gene promoter induction for MMP-2 and MMP-9 after MI. MI was induced in transgenic mice in which the MMP-2 or MMP-9 promoter sequence was fused to the beta-galactosidase reporter, and reporter level was assayed up to 28 days after MI. Myocardial localization with respect to cellular sources of MMP-2 and MMP-9 promoter induction was examined. After MI, LV diameter increased by 70% (P < 0.05), consistent with LV remodeling. beta-Galactosidase staining in MMP-2 reporter mice was increased by 1 day after MI and increased further to 64 +/- 6% of LV epicardial area by 7 days after MI (P < 0.05). MMP-2 promoter activation occurred in fibroblasts and myofibroblasts in the MI region. In MMP-9 reporter mice, promoter induction was detected after 3 days and peaked at 7 days after MI (53 +/- 6%, P < 0.05) and was colocalized with inflammatory cells at the peri-infarct region. Although MMP-2 promoter activation was similarly distributed in the MI and border regions, activation of the MMP-9 promoter was highest at the border between the MI and remote regions. These unique findings visually demonstrated that activation of the MMP-2 and MMP-9 gene promoters occurs in a distinct spatial relation with reference to the MI region and changes in a characteristic time-dependent manner after MI.

Selective reduction of fibrotic markers in repairing corneas of mice deficient in Smad3.

The cytokine transforming growth factor-beta (TGF-beta) is a key mediator of fibrosis in all organs. Expression of fibrotic markers in repairing cutaneous wounds is reduced in mice lacking Smad3, a downstream cytoplasmic mediator of TGF-beta signaling (Ashcroft et al., 1999, Nat Cell Biol 1(5):260-266). This is correlated with a reduction in inflammation, and thus in the blood elements thought to be a significant source of TGF-beta at the wound site, the principle form being TGF-beta1. Since the major cellular source of TGF-beta in corneal wounds is the epithelium, and the principal isoform is TGF-beta2, we investigated whether Smad3 deficiency has similar anti-fibrotic effects on corneal repair. In contrast to the situation of cutaneous repair, expression of the fibrotic marker, fibronectin, was equivalent in corneal repair tissue of Smad3-/- mice as compared to their +/- littermates, even though expression of a second fibrotic marker not previously examined in cutaneous wounds, alpha-smooth muscle (sm) actin, was reduced. Also unlike in cutaneous wounds, the inflammatory response was unaffected. These differences between corneal and cutaneous repair correlated with the lack of apparent change in the levels of corneal TGF-beta2. There was a significant reduction of alpha-sm actin expression in stromal cell cultures established from Smad3-/- mice as compared to their +/- littermates, but the rate of cell proliferation stimulated by TGF-beta, as well as expression of fibronectin, was unaffected. Therefore, a deficiency in Smad3 has different effects on corneal and cutaneous repair, probably due to the difference in cellular source and principal isoform of the TGF-beta involved.

Large spot endolaser for retinal photocoagulation and transvitreal thermotherapy.

BACKGROUND AND OBJECTIVE: Diode laser transpupillary thermotherapy can be used for the treatment and choroidal tumors. A large spot endolaser probe was developed for endophotocoagulation and transvitreal thermotherapy. The aim of this study was to assess the probe's clinical performance for photocoagulation and transvitreal thermotherapy combined with macular elevation. MATERIALS AND METHODS: Endolaser with a divergent beam giving a 3 mm spot size on the retina was developed. Vitrectomy was performed on ten eyes of five Dutch Belted rabbits. Threshold for photocoagulation was determined for the diode (810 nm) laser in four eyes. In another six eyes, the retina was detached with balanced salt solution prior to laser irradiation. The tissue effects were monitored clinically and with photography and microscopy. RESULTS: Threshold photocoagulation was induced with 150 mW power, for 1 minute, in attached retina. Following retinal detachment, no coagulation occurred at 200 mW (suprathreshold) power for 1 minute. CONCLUSIONS: A large spot endolaser probe may be useful for endophotocoagulation. It generates more gradual photocoagulation than standard endolaser probes, giving a more controllable reaction over a larger area. This may be useful for treatment of large areas of the retina when treating retinal detachments or ischemic retinopathies. When detached retina was irradiated, no retinal damage occurred at suprathreshold power. This development may allow for intraoperative transvitreal thermotherapy of choroidal neovascularization while protecting the retina with intentional intraoperative detachment of the retina.

Molecular mechanisms controlling the fibrotic repair phenotype in cornea: implications for surgical outcomes.

PURPOSE: Incisional or ablation injury to the corneal stroma is repaired by deposition of a fibrotic tissue produced by activated keratocytes, whereas cells lost from the underlying stroma after epithelial abrasion are simply replaced by keratocyte replication without expression of fibrotic markers. The purpose of this study was to investigate mechanisms that determine this differential keratocyte response. METHODS: A penetrating keratectomy rabbit model was adapted for mice to study the fibrotic repair response. A mouse epithelial abrasion model was applied to study the stromal cell replacement response. A primary rabbit corneal cell culture model and an organotypic culture model were also used. RESULTS: When the epithelium was prevented from resurfacing the cornea after penetrating keratectomy, expression of fibrotic markers was considerably reduced. TGF-beta2 was determined to be a major substance produced by corneal epithelial cells capable of inducing the fibrotic phenotype. In the intact mouse cornea, TGF-beta2 was confined to the uninjured epithelium, but was released into the stroma during fibrotic repair. By contrast, TGF-beta1 was never found in the epithelium. When epithelial cells were cultured on a basement-membrane-like gel or allowed to deposit their own basement membrane in organotypic culture, TGF-beta2 production was reduced. Return of a basement membrane after wounding in vivo correlated with loss of the fibrotic phenotype. In the epithelial debridement injury model in which the basement membrane was left intact, TGF-beta2 remained confined to the corneal epithelium, consistent with the absence of a fibrotic phenotype. CONCLUSIONS: These data suggest that integrity of the basement membrane is a deciding factor in determining the regenerative character of corneal repair.

Tubulointerstitial nephritis and uveitis syndrome.

BACKGROUND: Uveitis in association with tubulointerstitial nephritis is a distinct clinical entity known as tubulointerstitial nephritis and uveitis(TINU) syndrome. The onset of uveitis most commonly follows the onset of the interstitial nephritis, but may also occur before or concurrently. The uveitis is usually bilateral, nongranulomatous, limited to the anterior segment, and generally responds well to topical or oral (when indicated) anti-inflammatory treatment. Interestingly, recurrent or chronic uveitis is common, in contrast to the tubulointerstitial nephritis, which typically resolves completely. CASE REPORT: Approximately 5 months after a biopsy confirmed the diagnosis of tubulointerstitial nephritis, a 13-year-old boy was brought to our clinic with symptoms of a red, photophobic right eye of 3 days duration. Examination revealed nongranulomatous anterior-segment inflammation in the right eye greater than the left. The uveitis responded very well to topical steroid and cycloplegic treatment. Follow-up examinations have shown a gradual decrease in the inflammation, with no ocular complications. CONCLUSION: TINU syndrome is an under-recognized disorder and may account for some cases of uveitis otherwise characterized as 'idiopathic." Since the uveitis may be the presenting sign in up to 36% of cases of TINU syndrome, it is important for eye care practitioners to consider this disorder when searching for systemic associations with uveitis. Prompt detection through referral or testing will allow speedy diagnosis and appropriate treatment for both the uveitis and the tubulointerstitial nephritis.

Deficiency in matrix metalloproteinase gelatinase B (MMP-9) protects against retinal ganglion cell death after optic nerve ligation.

Loss of retinal ganglion cells is the final end point in blinding diseases of the optic nerve such as glaucoma. To enable the use of mouse genetics to investigate mechanisms underlying ganglion cell loss, we adapted an experimental model of optic nerve ligation to the mouse and further characterized post-surgical outcome. We made the novel finding that apoptosis of retinal ganglion cells correlates with specific degradation of laminin from the underlying inner limiting membrane and an increase in gelatinolytic metalloproteinase activity. These changes co-localize with a specific increase in levels of the matrix metalloproteinase, gelatinase B (GelB; MMP-9). Using a transgenic mouse line harboring a reporter gene driven by the GelB promoter, we further show that increased GelB is controlled by activation of the GelB promoter. These findings led us to hypothesize that GelB activity plays a role in ganglion cell death and degradation of laminin. Applying the genetic approach, we demonstrate that GelB-deficient mice are protected against these pathological changes. This is the first report demonstrating a causal connection between GelB activity and pathological changes to the inner retina after optic nerve ligation.