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Background The “I COUGH” protocol is associated with improved postoperative pulmonary outcomes, and ambulation is an essential component. I COUGH is an acronym for Incentive spirometry, Coughing, Oral care, Understanding (patient and staff education), Getting-out-of-bed, and Head-of-bed elevation. This trial sought to enhance one component, specifically ambulation after operations. Methods Randomized trial of inpatients in a safety-net, academic medical center. The intervention group received standard I COUGH education along with text message reminders to ambulate postoperatively, whereas the control group received standard education alone. Postoperative walking frequency was compared to each participant’s ambulation on the day prior to enrollment. Results The intervention group had an average improvement of 1.8 ± 1.8 walks per day per patient, while the average change for the control group was 0.2 ± 1.0 walks per day per patient. This represents a 9-fold increase in ambulation for the intervention group (p = 0.03). Conclusions Implementation of text message reminders increased ambulation and improved adherence to the I COUGH protocol following operations. This system should be further investigated as an adjunct to postoperative care.

We report a case of a 70-year-old woman with a history of end-stage renal disease secondary to polycystic kidney disease with a previous failed transplant who presented for a cadaveric extraperitoneal renal transplant. The patient developed a progressively worsening bowel obstruction postoperatively and evidence of an obstruction was observed on computed tomography imaging with a transition point at the level of the sigmoid colon. Consequent to this, she underwent an exploratory laparotomy, which revealed kinking of the colon secondary to the compression between the transplanted and the left native polycystic kidneys. There were adhesive bands between the native kidney and the descending colon in the retroperitoneal space maintaining it in a fixed position mechanically. The addition of a retroperitoneal transplant exacerbated this kink and was responsible for the bowel obstruction. Her left colon was completely mobilized to relieve her obstruction, and owing to her bowel distension, her abdomen was left open for 2 days before returning to the operating room to remove her left native polycystic kidney to allow space for safe closure. This report highlights an extremely unusual cause of large bowel obstruction post–kidney transplantation.

Background: Coronavirus disease 2019 (COVID-19) is recognized as a multisystem disease affecting the whole body, with new complications from the disease being described on an almost-daily basis. Case Report: We report the case of a 50-year-old female with a medical history of diabetes and silicone breast implants who developed right-sided, multicentric breast masses after a prolonged hospitalization for COVID-19 infection complicated by renal failure requiring dialysis. The patient noted an onset of breast pain and masses, and subsequent imaging demonstrated multiple similar oval masses. She underwent biopsy and operative debridement of the lesions and recovered appropriately. Results were consistent with sterile abscesses that were considered secondary to a vasculitis-like process associated with COVID-19 infection. Conclusion: To our knowledge, this case is the first account of breast pathology associated with a diagnosis of COVID-19 in the medical literature and encourages systematic evaluations of patients with coronavirus infections, including breast examinations.

Solid pseudopapillary neoplasms of the pancreas are overwhelmingly benign tumors predominately observed in women in the third decade of life. However, their malignant potential, based on local recurrences and metastases, has brought into question the available evidence on their biological behavior. Solid pseudopapillary neoplasms have distanced themselves from other pancreatic tumors with varying morphological appearance, immune profile, and histogenesis. In review of the literature, PubMed was queried using search strings, including "solid pseudopapillary neoplasm" and "molecular," and "immunohistochemistry." Alternative searches were also conducted given the variability in tumor name, including "solid pseudopapillary tumor" and "Frantz tumor." This article provides an in-depth review into the molecular pathways that contribute to the pathogenesis of solid pseudopapillary neoplasms. It also discusses the implications of existing molecular pathways toward tumor aggressiveness and recurrence potential.

Text messaging is frequently employed in the outpatient setting to communicate with or send reminders to patients. However, there is a paucity of literature on the impact of text messaging on inpatient care. In this study, the use of text messaging in hospitalized patients is evaluated by assessing patient compliance to a post-operative bariatric protocol.This was a randomized controlled trial that studied compliance to a post-operative bariatric protocol in patients who underwent bariatric surgery at a tertiary, academic medical center between February and May 2021. Patients were randomized to either the control group, in which they received standard post-operative education alone or the Tulane Sending Texts, Advancing Results (STAR) intervention arm, in which participants received the same post-operative education along with two text message reminders to drink water, use their incentive spirometers, and ambulate (per post-operative instructions) on post-operative day (POD) # 0 and POD # 1. The primary outcome was compliance with the protocol, defined as the number of 1-oz cups of water consumed, incentive spirometry usage, and ambulation frequency and distance. Secondary outcomes include length of stay and complications.A total of 35 patients were enrolled in the study (17 control, 18 STAR intervention). There was no significant difference in age, BMI, or type of surgery performed between the two groups. Clear liquid consumption was significantly higher in the STAR intervention group with an average of 27.7 ± 3.5 cups as compared to 18.2 ± 8.9 in the control group (p lt; 0.001). Similarly, statistically significant increases in incentive spirometry usage (p lt; 0.01) and ambulation distance and frequency (p lt; 0.02) were observed in the STAR intervention group.While patients are in the hospital, text messaging can improve compliance to post-operative protocols. Peri-operative text messaging can enhance patient education and communication.

Trauma patients receiving massive transfusion protocol (MTP) are at risk of citrate-induced hypocalcemia and hyperkalemia. Here we evaluate potassium (K), ionized calcium (iCa), and K/iCa ratio as predictors of mortality.This retrospective study includes all adult trauma patients who received MTP within 1 h at our level I trauma center between 2014 and 2019. Receiver operating characteristic curve analysis assessed predictive accuracy of K/iCa ratio at admission on 120-day mortality.Of 614 patients, 146 received MTP within 1 h and 38 expired. Patients who expired had higher K/iCa ratio than survivors (median [IQR] = 5.7 [3.8-7.2] vs 3.7 [3.1-4.9], p 0.001). Area under the curve of K/iCa was 0.72 (95%CI = 0.62-0.82, p 0.001) with sensitivity = 63.2% and specificity = 77.6%. At the optimum K/iCa cutoff (5.07), patients with high ratios had 4 times higher mortality risk (HR = 3.97, 95%CI = 1.89-8.32, p 0.001).Elevated K/iCa ratio was an independent predictor of mortality in trauma patients managed with MTP.

Background Percutaneous cholecystostomy (PC) tube is a preferred option in acute cholecystitis for patients who are high risk for cholecystectomy (CCY). There are no evidence-based guidelines for patient care after PC. We identified the predictors of disease recurrence and successful interval CCY. Methods A retrospective review of 145 PC patients between 2008 and 2016 at a tertiary hospital was performed. Primary outcomes included mortality, readmissions, hospital and intensive care unit length of stay (LOS), disease recurrence, and interval CCY. Results There were 96 (67%) calculous and 47 (33%) acalculous cholecystitis cases. Seventy-two (49%) had chronic and 73 (51%) had acute prohibitive risks as an indication for PC. There were 54 (37%) periprocedural complications, which most commonly were dislodgements. Twenty-six (18%) patients had a recurrence at a median time of 65 days. Calculous cholecystitis (odds ratio [OR] 3.44, P = 0.038) and purulence in the gallbladder (OR 3.77, P = 0.009) were predictors for recurrence. Forty-one (28%) patients underwent interval CCY. Patients with acute illness were likely to undergo interval CCY (OR 6.67, P = 0.0002). Patients with acalculous cholecystitis had longer hospital LOS (16 versus 8 days) and intensive care unit LOS (2 versus 0 days), and higher readmission rates (OR 2.42, P = 0.02). Thirty-day mortality after PC placement was 9%. Patients receiving interval CCY were noted to have increased survival compared to PC alone. However, this should not be attributed to interval CCY alone in absence of randomization in this study. Conclusions Calculous cholecystitis and purulence in the gallbladder are independent predictors of acute cholecystitis recurrence. Acute illness is a strong predictor of successful interval CCY. The association of interval CCY and prolonged survival in patients with PC as noted in this study should be further assessed in future prospective randomized trials.

Hyaluronan (HA), a major component of the extracellular matrix, is secreted by airway structural cells. Airway fibroblasts in allergic asthma secrete elevated levels of HA in association with increased HA synthase 2 (HAS2) expression. Thus, we hypothesized that HA accumulation in the airway wall may contribute to airway remodeling and hyperresponsiveness in allergic airways disease. To examine this hypothesis, transgenic mice in which the α-smooth muscle actin (α-SMA) promoter drives HAS2 expression were generated. Mixed male and female α-SMA–HAS2 mice (HAS2+ mice, n = 16; HAS2− mice, n = 13) were sensitized via intraperitoneal injection and then chronically challenged with aerosolized ovalbumin (OVA) for 6 weeks. To test airway responsiveness, increasing doses of methacholine were delivered intravenously and airway resistance was measured using the forced oscillation technique. HA, cytokines, and cell types were analyzed in bronchoalveolar lavage fluid, serum, and whole lung homogenates. Lung sections were stained using antibodies specific for HA-binding protein (HABP) and α-SMA, as well as Masson’s trichrome stain. Staining of lung tissue demonstrated significantly increased peribronchial HA, α-SMA, and collagen deposition in OVA-challenged α-SMA–HAS2+ mice compared with α-SMA–HAS2− mice. Unexpectedly, OVA-challenged α-SMA–HAS2+ mice displayed significantly reduced airway responsiveness to methacholine compared with similarly treated α-SMA–HAS2− mice. The total numbers of inflammatory cell types in the bronchoalveolar lavage fluid did not differ significantly between OVA-challenged α-SMA–HAS2+ mice and α-SMA–HAS2− mice. We conclude that allergen-challenged mice that overexpress HAS2 in myofibroblasts and smooth muscle cells develop increased airway fibrosis, which lessens airway hyperresponsiveness to bronchoconstrictors.

8-Oxo-2'-deoxyguanosine (OdG) is an abundant DNA lesion produced during oxidative damage to DNA. It can form relatively stable base pairs with both dC and dA that mimic natural dG:dC and dT:dA base pairs, respectively. Thus, when in the template strand, OdG can direct the insertion of either dCTP or dATP during replication, the latter of which can lead to a dG → T transversion. The potential for OdG to cause mutation is dependent on the preference for dCTP or dATP insertion opposite OdG, as well as the ability to extend past the resulting base pairs. The C2-amine and C8-oxygen could play major roles during these reactions since both would lie outside the Watson-Crick cognate base pairs shape in the major groove when OdG base pairs to dA and dC, respectively, and both have the ability to form strong interactions, like hydrogen bonds. To gain a more generalized understanding of how the C2-amine and C8-oxygen of OdG affect its mutagenic potential, the incorporation opposite and extension past seven analogues of dG/OdG that vary at C2 and/or C8 were characterized for three DNA polymerases, including an exonuclease-deficient version of the replicative polymerase from RB69 (RB69), human polymerase (pol) β, and polymerase IV from Sulfolobus solfataricus P2 (Dpo4). Based on the results from these studies, as well as those from previous studies with RB69, pol β, Dpo4, and two A-family polymerases, the influence of the C2-amine and C8-oxygen during each incorporation and extension reaction with each polymerase is discussed. In general, it appears that when the C2-amine and the C8-oxygen are in the minor groove, they allow OdG to retain interactions that are normally present during insertion and extension. However, when the two groups are in the major groove, they each tend to form novel active site interactions, both stabilizing and destabilizing, that are not present during insertion and extension with natural DNA.

The bacterial repair enzyme MutT hydrolyzes the damaged nucleotide OdGTP (the 5'-triphosphate derivative of 8-oxo-2'-deoxyguanosine; OdG), which is a known mutagen and has been linked to antibacterial action. Previous work has indicated important roles for the C8-oxygen, N7-hydrogen, and C2-exocyclic amine during OdGTP recognition by MutT. In order to gain a more nuanced understanding of the contribution of these three sites to the overall activity of MutT, we determined the reaction parameters for dGTP, OdGTP, and nine of their analogues using steady state kinetics. Our results indicate that overall high reaction efficiencies can be achieved despite altering any one of these sites. However, altering two or more sites leads to a significant decrease in efficiency. The data also suggest that, similar to another bacterial OdG repair enzyme, MutM, a specific carbonyl in the enzyme can not only promote activity by forming an active site hydrogen bond with the N7-hydrogen of OdGTP, but can also hinder activity through electrostatic repulsion with the N7-lone pair of dGTP.

Elastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV1, 89 ± 3% predicted) and 30 normal control subjects (FEV1, 102 ± 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert's resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV1/FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13-induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13-induced suppression of ELN expression in airway fibroblasts.

8-Oxo-2'-deoxyguanosine (OdG) is a prominent DNA lesion produced from the reaction of 2'-deoxyguanosine (dG) with reactive oxygen species. While dG directs the insertion of only dCTP during replication, OdG can direct the insertion of either dCTP or dATP, allowing for the production of dG → dT transversions. When replicated by Klenow fragment-exo (KF-exo), OdG preferentially directs the incorporation of dCTP over dATP, thus decreasing its mutagenic potential. However, when replicated by a highly related polymerase, the large fragment of polymerase I from Bacillus stearothermophilus (BF), dATP incorporation is preferred, and a higher mutagenic potential results. To gain insight into the reasons for this opposite preference and the effects of the C2, N7, and C8 positions on OdG mutagenicity, single-nucleotide insertions of dCTP and/or dATP opposite dG, OdG, and seven of their analogues were examined by steady state kinetics with both KF-exo and BF. Results from these studies suggest that the two enzymes behave similarly and are both sensitive not only to steric and electronic changes within the imidazole ring during both dCTP and dATP incorporation but also to the presence of the C2-exocyclic amine during dATP incorporation. The difference in incorporation preference opposite OdG appears to be due to a somewhat increased sensitivity to structural perturbations during dCTP incorporation with BF. Single-nucleotide extensions past the resulting base pairs were also studied and were not only similar between the two enzymes but also consistent with published ternary crystallographic studies with BF. These results are analyzed in the context of previous biochemical and structural studies, as well as stability studies with the resulting base pairs.

L3 Leptin Modulates Airway Remodeling Processes and Responses to Interleukin-13 in Lung Fibroblasts in a Murine Model of Chronic Allergic Airways Disease Jennifer L. Ingram, Robert W. Sigmon, Barbara Theriot, Michael Ghio, Akhil Hegde, Dave Francisco, Julia K. L. Walker, Monica Kraft, MD; Duke University, Durham, NC. RATIONALE: Obese asthma is characterized by late-onset disease and reduced T-helper 2 (TH2)-driven inflammation. Leptin is an adipokine produced in elevated levels in obese individuals. Interleukin-13 (IL-13) is a TH2 cytokine that directs airway remodeling in asthma, including subepithelial fibrosis. We hypothesized that leptin acts to suppress lung fibroblast responses to IL-13 in obese asthma. METHODS: Wildtype (C57BL6), leptin-resistant (db/db), and leptindeficient (ob/ob) mice (n53 per group) were intranasally administered house dust mite (HDM) allergen (2.5 mg/mL) or saline as control 5 days/ week for 6 weeks. Lung mechanics were measured using the forced oscillation technique, and Newtonian resistance was calculated. Lung sections were stained with Masson’s trichrome. Lung fibroblasts were cultured from digested lung tissue and exposed to serum-free media or 50 ng/mL IL-13 for 24 hours. Lung fibroblast invasion and migration were determined using Matrigel assays, and mRNA expression was analyzed using quantitative RT-PCR. RESULTS: Following exposure to HDM, peribronchiolar trichrome staining and IL-13-induced lung fibroblast invasion and migration were significantly reduced in ob/ob and db/db mice as compared to wildtype (p