Suture fixation of traumatic rib fracture flail segment with Klebsiella osteomyelitis.

We report the case of a 71-year-old male who initially presented with urosepsis and was found to have a rib fracture of his right 6th rib with a flail segment and an associated abscess. Given the concern for infection, surgical rib fixation with titanium plating was not pursued during the washout of his abscess and instead, he successfully underwent rib fracture stabilization with bilateral suture transfixation. He was continued on a prolonged course of antibiotics for Klebsiella pneumonia osteomyelitis and was discharged uneventfully with optimal pain control and adequate respiratory effort.

Endovascular covered stent graft repair by through-and-through snaring of an acute traumatic femoral-femoral arteriovenous fistula following a gunshot wound.

Arteriovenous fistula (AVF) formation after penetrating injury underscores a rare and challenging complication of vascular trauma. Traumatic AVFs have various clinical presentations and reported methods of repair. Although open surgical repair is the most frequently used method of repair, the advancement of endovascular techniques has been increasingly used during the past 3 decades. We report a case of an acute traumatic AVF of the superficial femoral artery and superficial femoral vein from a gunshot wound repaired with a unique endovascular technique involving snaring to establish through-and-through access to allow deployment of a covered stent graft.

Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness.

Epigenetic control of cellular transcription and phenotype is influenced by changes in the cellular microenvironment, yet how mechanical cues from these microenvironments precisely influence epigenetic state to regulate transcription remains largely unmapped. Here, we combine genome-wide epigenome profiling, epigenome editing, and phenotypic and single-cell RNA-seq CRISPR screening to identify a new class of genomic enhancers that responds to the mechanical microenvironment. These 'mechanoenhancers' could be active on either soft or stiff extracellular matrix contexts, and regulated transcription to influence critical cell functions including apoptosis, mechanotransduction, proliferation, and migration. Epigenetic editing of mechanoenhancers on rigid materials tuned gene expression to levels observed on softer materials, thereby reprogramming the cellular response to the mechanical microenvironment. These editing approaches may enable the precise alteration of mechanically-driven disease states.

DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks.

Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in the establishment and maintenance of centromeric chromatin through the deposition of the histone variant H3.3. ATRX and DAXX have also evolved mutually-independent functions in transcription and chromatin dynamics. Here, using paediatric glioma and pancreatic neuroendocrine tumor cell lines, we identify a novel ATRX-independent function for DAXX in promoting genome stability by preventing transcription-associated R-loop accumulation and DNA double-strand break formation at centromeres. This function of DAXX required its interaction with histone H3.3 but was independent of H3.3 deposition and did not reflect a role in the repression of centromeric transcription. DAXX depletion mobilized BRCA1 at centromeres, in line with BRCA1 role in counteracting centromeric R-loop accumulation. Our results provide novel insights into the mechanisms protecting the human genome from chromosomal instability, as well as potential perspectives in the treatment of cancers with DAXX alterations.

Celiac artery occlusion from median arcuate ligament compression complicating a hemorrhagic duodenal ulcer repair.

We present a case of a hemorrhagic duodenal ulcer complicated by occlusion of the celiac artery (CA) by acute median arcuate ligament (MAL) compression. Angiography revealed retrograde flow through the gastroduodenal artery (GDA) to the hepatic artery, with occlusion at the CA origin. This unique presentation required coordinated release of the MAL to reestablish antegrade CA flow before pyloroplasty and GDA ligation. The presence of preexisting MAL compression of the CA should be considered during the repair of bleeding duodenal ulcers through embolization or ligation of the GDA, because impaired CA perfusion could result in foregut ischemia.

A paradoxical internal hernia at Brolin's anti-obstruction stitch following Roux-en-Y gastric bypass: a case report.

Internal hernias are a rare but morbid complication following Roux-en-Y gastric bypass surgery. The incorporation of Brolin's anti-obstruction stitch has historically demonstrated a significant reduction in the incidence of internal hernias following Roux-en-Y gastric bypass. We present an ironic and unique case of a patient with small bowel herniation into a defect between Brolin's stitch and the stapled closed common enterotomy of the jejunojejunostomy and technical considerations to decrease internal hernias at this site in the future.

Operative technique for a successful laparoscopic en-bloc resection of gastrogastric fistula following roux-en-Y gastric bypass.

Gastrogastric fistulas are rare complications following Roux-en-Y gastric bypass surgery and are characterized by a fistulous connection between the gastric pouch and the remnant stomach. The presentation is often variable and a high-index of suspicion must be maintained for accurate and timely diagnosis. In this case report, we provide a detailed review of the technical steps taken to successfully resect a gastrogastric fistula en-bloc laparoscopically with an unremarkable post-operative course.

Fabrication-robust silicon photonic devices in standard sub-micron silicon-on-insulator processes.

Perturbations to the effective refractive index from nanometer-scale fabrication variations in waveguide geometry plague high index-contrast photonic platforms; this includes the ubiquitous sub-micron silicon-on-insulator (SOI) process. Such variations are particularly troublesome for phase-sensitive devices, such as interferometers and resonators, which exhibit drastic changes in performance as a result of these fabrication-induced phase errors. In this Letter, we propose and experimentally demonstrate a design methodology for dramatically reducing device sensitivity to silicon width variations. We apply this methodology to a highly phase-sensitive device, the ring-assisted Mach-Zehnder interferometer (RAMZI), and show comparable performance and footprint to state-of-the-art devices, while substantially reducing stochastic phase errors from etch variations. This decrease in sensitivity is directly realized as energy savings by significantly reducing the required corrective thermal tuning power, providing a promising path toward ultra-energy-efficient large-scale silicon photonic circuits.

Gunshot Wound to the Right Superior Pulmonary Vein With Bullet Embolization to the Aortic Bifurcation: Emergent Surgical Repair.

Bullet embolization is a rare complication of gunshot wound injuries with most of the literature consisting of case reports. We report a case regarding bullet embolization to the distal aorta following entry into the right superior pulmonary vein as a result of a gunshot wound to the posterior chest. The patient presented with signs of lower extremity ischemia. Imaging revealed an intrabdominal bullet at the level of L4 and laparatomy identified the bullet to be within the aorta at the bifurcation. Successful repair of the cardiac injury and removal of the intra-aortic bullet were achieved by sternotomy and laparatomy.

In-situ bypass is associated with superior infection-free survival compared with extra-anatomic bypass for the management of secondary aortic graft infections without enteric involvement.

OBJECTIVE: The optimal revascularization modality following complete resection of aortic graft infection (AGI) without enteric involvement remains unclear. The purpose of this investigation is to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients undergoing complete excision of AGI. METHODS: A retrospective, multi-institutional study of AGI from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and perioperative variables were recorded. The primary outcome was infection-free survival. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariable analyses were performed. RESULTS: A total of 241 patients at 34 institutions from seven countries presented with AGI during the study period (median age, 68 years; 75% male). The initial aortic procedures that resulted in AGI were 172 surgical grafts (71%), 66 endografts (27%), and three unknown (2%). Of the patients, 172 (71%) underwent complete excision of infected aortic graft material followed by in situ (in-line) bypass (ISB), including antibiotic-treated prosthetic graft (35%), autogenous femoral vein (neo-aortoiliac surgery) (24%), and cryopreserved allograft (41%). Sixty-nine patients (29%) underwent extra-anatomic bypass (EAB). Overall median Kaplan-Meier estimated survival was 5.8 years. Perioperative mortality was 16%. When stratified by ISB vs EAB, there was a significant difference in Kaplan-Meier estimated infection-free survival (2910 days; interquartile range, 391-3771 days vs 180 days; interquartile range, 27-3750 days; P < .001). There were otherwise no significant differences in presentation, comorbidities, or perioperative variables. Multivariable Cox regression showed lower infection-free survival among patients with EAB (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.6-3.6; P < .001), polymicrobial infection (HR, 2.2; 95% CI, 1.4-3.5; P = .001), methicillin-resistant Staphylococcus aureus infection (HR, 1.7; 95% CI, 1.1-2.7; P = .02), as well as the protective effect of omental/muscle flap coverage (HR, 0.59; 95% CI, 0.37-0.92; P = .02). CONCLUSIONS: After complete resection of AGI, perioperative mortality is 16% and median overall survival is 5.8 years. EAB is associated with nearly a two and one-half-fold higher reinfection/mortality compared with ISB. Omental and/or muscle flap coverage of the repair appear protective.

Impact of clinical characteristics on human chorionic gonadotropin regression after molar pregnancy.

OBJECTIVES: This study aimed to determine the effects of age, race/ethnicity, body mass index, and contraception on human chorionic gonadotropin (hCG) regression following the evacuation of a molar pregnancy. METHODS: This was a retrospective cohort study of 277 patients with molar pregnancies between January 1, 1994 and December 31, 2015. The rate of hCG regression was estimated using mixed-effects linear regression models on daily log-transformed serum hCG levels after evacuation. RESULTS: There were no differences in hCG half-lives among age (p=0.13) or race/ethnicity (p=0.16) groups. Women with obesity and hormonal contraceptive use demonstrated faster hCG regression than their counterparts (3.2 versus. 3.7 days, p=0.02 and 3.4 versus. 4.0 days, p=0.002, respectively). CONCLUSION: Age and race/ethnicity were not associated with hCG regression rates. Hormonal contraceptive use and obesity were associated with shorter hCG half-lives, but with unlikely clinical significance. It is important to understand whether the clinical characteristics of patients may influence the hCG regression curve, as it has been proposed as a way to predict the risk of gestational trophoblastic neoplasia.

The Female Reproductive Tract Microbiome-Implications for Gynecologic Cancers and Personalized Medicine.

The microbial colonization of the lower female reproductive tract has been extensively studied over the past few decades. In contrast, the upper female reproductive tract including the uterine cavity and peritoneum where the ovaries and fallopian tubes reside were traditionally assumed to be sterile under non-pathologic conditions. However, recent studies applying next-generation sequencing of the bacterial 16S ribosomal RNA gene have provided convincing evidence for the existence of an upper female reproductive tract microbiome. While the vaginal microbiome and its importance for reproductive health outcomes has been extensively studied, the microbiome of the upper female reproductive tract and its relevance for gynecologic cancers has been less studied and will be the focus of this article. This targeted review summarizes the pertinent literature on the female reproductive tract microbiome in gynecologic malignancies and its anticipated role in future research and clinical applications in personalized medicine.

Long-term outcomes of transposed femoral vein arteriovenous fistula for abandoned upper extremity dialysis access.

BACKGROUND: The number and longevity of patients with end-stage renal disease requiring dialysis access have continued to increase, leading to challenging situations, including exhausted upper extremity access and severe central venous stenosis. This has led to an increase in the use of alternative access sites, including the lower extremities. The transposed femoral vein arteriovenous fistula for dialysis access is a previously described alternative, although limited data are available on its long-term patency. METHODS: Patients treated with a transposed femoral vein fistula were retrospectively reviewed. A transposed femoral vein fistula was created by harvesting the femoral vein and transposing it to the distal superficial femoral artery at the level of the adductor canal. The demographic information, perioperative characteristics, complications, and long-term outcomes were recorded and analyzed. RESULTS: A total of 21 patients had undergone transposed femoral vein fistula for dialysis access after an average of 5.3 ± 2.8 failed dialysis access procedures and a duration of 6.1 ± 4.9 years from the initiation of dialysis. The average age at the procedure was 53.5 ± 12.8 years. Ten patients (47.6%) had a history of diabetes mellitus and nine (42.9%) had a history of coronary artery disease. Technical success was achieved in 100% of cases, and 16 patients (76.2%) were discharged with anticoagulation therapy. The primary patency at 1, 3, and 5 years was 93%, 74%, and 74%, respectively. The secondary patency at 1, 3, and 5 years was 100%, 89%, and 89%, respectively. Two patients had compartment syndrome requiring fasciotomy, and six patients experienced wound complications. CONCLUSIONS: Transposed femoral vein fistula for dialysis access is a viable alternative for patients with an exhausted upper extremity access, with good long-term patency.

Push-pull microring-assisted space-and-wavelength selective switch.

We introduce a novel design of a space-and-wavelength selective switch based on microring-assisted Mach-Zehnder interferometers. Multiple pairs of overcoupled microring resonators are incorporated as efficient and narrowband phase shifters and are driven in push-pull scheme. We design and demonstrate a 2×2×2λ elementary switch block with full spatial and spectral switching capabilities. The switching device's cross talk suppression and extinction ratio both exceed 21 dB. We measure over 75 GHz optical bandwidth per channel and less than 1.5 dB power penalty at 10-9 BER when two 32 Gbps on-off keying signals are loaded simultaneously. This new class of switching elements can further enable compact and high-performance space-and-wavelength selective switch fabrics without the need for wavelength (de)multiplexers or parallel switching planes.

Functional Loss of ATRX and TERC Activates Alternative Lengthening of Telomeres (ALT) in LAPC4 Prostate Cancer Cells.

A key hallmark of cancer, unlimited replication, requires cancer cells to evade both replicative senescence and potentially lethal chromosomal instability induced by telomere dysfunction. The majority of cancers overcome these critical barriers by upregulating telomerase, a telomere-specific reverse transcriptase. However, a subset of cancers maintains telomere lengths by the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. The presence of ALT is strongly associated with recurrent cancer-specific somatic inactivating mutations in the ATRX-DAXX chromatin-remodeling complex. Here, we generate an ALT-positive adenocarcinoma cell line following functional inactivation of ATRX and telomerase in a telomerase-positive adenocarcinoma cell line. Inactivating mutations in ATRX were introduced using CRISPR-cas9 nickase into two prostate cancer cell lines, LAPC-4 (derived from a lymph node metastasis) and CWR22Rv1 (sourced from a xenograft established from a primary prostate cancer). In LAPC-4, but not CWR22Rv1, abolishing ATRX was sufficient to induce multiple ALT-associated hallmarks, including the presence of ALT-associated promyelocytic leukemia bodies (APB), extrachromosomal telomere C-circles, and dramatic telomere length heterogeneity. However, telomerase activity was still present in these ATRXKO cells. Telomerase activity was subsequently crippled in these LAPC-4 ATRXKO cells by introducing mutations in the TERC locus, the essential RNA component of telomerase. These LAPC-4 ATRXKO TERCmut cells continued to proliferate long-term and retained ALT-associated hallmarks, thereby demonstrating their reliance on the ALT mechanism for telomere maintenance. IMPLICATIONS: These prostate cancer cell line models provide a unique system to explore the distinct molecular alterations that occur upon induction of ALT, and may be useful tools to screen for ALT-specific therapies.

Cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence.

A new evaluation of previously published data suggested to us that the accumulation of mutations might slow, rather than increase, as individuals age. To explain this unexpected finding, we hypothesized that normal stem cell division rates might decrease as we age. To test this hypothesis, we evaluated cell division rates in the epithelium of human colonic, duodenal, esophageal, and posterior ethmoid sinonasal tissues. In all 4 tissues, there was a significant decrease in cell division rates with age. In contrast, cell division rates did not decrease in the colon of aged mice, and only small decreases were observed in their small intestine or esophagus. These results have important implications for understanding the relationship between normal stem cells, aging, and cancer. Moreover, they provide a plausible explanation for the enigmatic age-dependent deceleration in cancer incidence in very old humans but not in mice.

A unique telomere DNA expansion phenotype in human retinal rod photoreceptors associated with aging and disease.

We have identified a discrete, focal telomere DNA expansion phenotype in the photoreceptor cell layer of normal, non-neoplastic human retinas. This phenotype is similar to that observed in a subset of human cancers, including a large fraction of tumors of the central nervous system, which maintain their telomeres via the non-telomerase-mediated alternative lengthening of telomeres (ALT) mechanism. We observed that these large, ultra-bright telomere DNA foci are restricted to the rod photoreceptors and are not observed in other cell types. Additionally, focus-positive rod cells are dispersed homogeneously throughout the posterior retinal photoreceptor cell layer and appear to be human-specific. We examined 108 normal human retinas obtained at autopsy from a wide range of ages. These large, ultra-bright telomere DNA foci were not observed in infants before 6 months of age; however, the prevalence of focus-positive rod cells dramatically increased throughout life. To investigate associations between this phenotype and retinal pathology, we assessed adult glaucoma (N = 29) and diabetic retinopathy (N = 38) cases. Focus-positive rod cells were prominent in these diseases. When compared to the normal group, after adjusting for age, logistic regression modeling revealed significantly increased odds of falling in the high category of focus-positive rod cells for glaucoma and diabetic retinopathy. In summary, we have identified a dramatic telomere alteration associated with aging and diseases affecting the retina.

Ureteroarterial Fistula in a Patient with an Ileal Conduit and Chronic Nephroureteral Catheter.

Background: Ureteroarterial fistula (UAF) is a rare and potentially devastating diagnosis most often associated with a combination of pelvic oncologic or vascular surgery, radiation, and chronic ureteral stents. Herein we discuss a patient with an ileal conduit urinary diversion and left nephroureteral (NU) catheter who presented with gross hematuria and hemodynamic instability. He underwent multiple negative radiologic investigations and his clinical course highlights the need for a high index of suspicion for UAF and multidisciplinary coordination with vascular surgery and interventional radiology. Case Presentation: Our patient is a 64-year-old male with a history of bladder cancer and atrial fibrillation on rivaroxiban who underwent cystoprostatectomy with ileal conduit urinary diversion. His postoperative course was complicated by subsequent mid-distal stricture of his left ureter, which was managed with balloon dilatation and a chronic indwelling NU catheter. He underwent a routine catheter exchange ∼1 year postradical cystectomy and subsequently experienced intermittent gross hematuria. He presented 5 weeks later with profound hematuria and clots through his urostomy accompanied by flank pain, weakness, and tachycardia. Throughout his hospital course he underwent two CT angiograms and a formal provocative angiogram that were all negative. He was taken to the operating room (OR) for attempted antegrade ureteroscopy, which was aborted because of pulsatile bleeding observed upon withdrawal of his stent. In collaboration with vascular surgery, he was eventually taken for provocative angiogram and covered stent graft placement that resolved the hematuria. Conclusion: This case highlights the diagnostic and care coordination challenges in patients with UAF. A high suspicion should be maintained in patients with hematuria and indwelling stents with a history of pelvic surgery and/or radiation.

ATRX loss induces multiple hallmarks of the alternative lengthening of telomeres (ALT) phenotype in human glioma cell lines in a cell line-specific manner.

Cancers must maintain their telomeres at lengths sufficient for cell survival. In several cancer subtypes, a recombination-like mechanism termed alternative lengthening of telomeres (ALT), is frequently used for telomere length maintenance. Cancers utilizing ALT often have lost functional ATRX, a chromatin remodeling protein, through mutation or deletion, thereby strongly implicating ATRX as an ALT suppressor. Herein, we have generated functional ATRX knockouts in four telomerase-positive, ALT-negative human glioma cell lines: MOG-G-UVW, SF188, U-251 and UW479. After loss of ATRX, two of the four cell lines (U-251 and UW479) show multiple characteristics of ALT-positive cells, including ultrabright telomeric DNA foci, ALT-associated PML bodies, and c-circles. However, telomerase activity and overall telomere length heterogeneity are unaffected after ATRX loss, regardless of cellular context. The two cell lines that showed ALT hallmarks after complete ATRX loss also did so upon ATRX depletion via shRNA-mediated knockdown. These results suggest that other genomic or epigenetic events, in addition to ATRX loss, are necessary for the induction of ALT in human cancer.

Update on primary HPV screening for cervical cancer prevention.

In the coming decade, primary testing for human papillomavirus (HPV) will likely become the standard of care for cervical cancer screening in both low- and high-resource settings. This change comes as evidence has accumulated to support HPV testing as more sensitive to detect high-grade precancerous disease. Furthermore, negative HPV testing has demonstrated a lower cumulative incidence of cervical intraepithelial neoplasia (CIN) grade 3 or worse pathology (CIN3+) when compared to negative "Pap smears" over several rounds of screening. While many countries have begun pilot programs to transition to primary HPV screening and some have completely transitioned for certain uses, there remains much to be refined about this tool for cervical cancer prevention, as evidenced by the myriad of ways it is being utilized. In the United States, the use of primary HPV testing to screen for cervical cancer has been supported by a consensus statement from the Society of Gynecologic Oncologists and American Society for Colposcopy and Cervical Pathology along with experts from American College of Obstetricians and Gynecologists/American Cancer Society/American Society of Cytopathology/College of American Pathologists/and American Society for Clinical Pathology. Additionally, recently proposed United States Preventive Services Task Force guideline changes, and recent Food and Drug Administration approval of the second test for primary HPV screening highlight the broadening availability and support for primary HPV screening. The aim of this review is to summarize the evidence supporting the safety and effectiveness of primary HPV screening and its use in different high-resource settings.