Hemorrhage-induced intestinal damage is complement independent in Helicobacter hepaticus infected mice

With over half of the world population infected, Helicobacter infection is an important public health issue associated with gastrointestinal cancers and inflammatory bowel disease. Animal studies indicate that complement and oxidative stress play a role in Helicobacter infections. Hemorrhage induces tissue damage which is attenuated by blockade of either complement activation or oxidative stress products. Therefore, we hypothesized that chronic Helicobacter hepaticus infection would modulate hemorrhage-induced intestinal damage and inflammation. To test this hypothesis, we examined hemorrhage-induced jejunal damage and inflammation in uninfected and H. hepaticus infected mice. H. hepaticus infection increased hemorrhage-induced mid-jejunal mucosal damage despite attenuating complement activation. In addition, infection alone increased chemokine secretion, changing the hemorrhage-induced neutrophil infiltration to a macrophage-mediated inflammatory response. The hemorrhage-induced macrophage infiltration correlated with increased secretion of tumor necrosis factor-α (TNF-α³) and nitric oxide (NO) in the infected mice. Together these data indicate that Helicobacter infection modulates the mechanism of hemorrhage-induced intestinal damage and inflammation from a complement-mediated response to a macrophage response with elevated TNF-α and NO. These data indicate that chronic, low level infections change the response to trauma and should be considered when designing and administering therapeutics

Macrophage produced IL-12p70 mediates hemorrhage-induced damage in a complement dependent manner

Hemorrhage and hemorrhagic shock instigate intestinal damage and inflammation. Multiple components of the innate immune response, including complement and neutrophil infiltration, are implicated in this pathology. To investigate the interaction of complement activation and other components of the innate immune response during hemorrhage, we treated mice post-hemorrhage with CR2-fH, a targeted inhibitor of the alternative complement pathway and assessed intestinal damage and inflammation 2 h after hemorrhage. In wildtype mice, CR2-fH attenuated hemorrhage-induced, mid-jejunal damage and inflammation as determined by decreased mucosal damage, macrophage infiltration, LTB[subscript 4], IL-12p40, and TNF-α production. The critical nature of intestinal macrophage infiltration and activation in the response to hemorrhage was further determined using mice pre-treated with clodronate containing liposomes. The absence of either macrophages or IL-12p70 attenuated intestinal damage. These data suggest that complement activation and macrophage infiltration with IL-12p70 production are critical to hemorrhage induced mid-jejunal damage and inflammation

A unique case of Miller Fisher-Guillain-Barré overlap syndrome in a liver transplant recipient

Guillain-Barré syndrome (GBS) is an ascending demyelinating polyneuropathy often associated with recent infection. Miller Fisher syndrome represents a variant with predominant facial and cranial nerve involvement, although Miller Fisher and Guillain-Barré overlap syndromes can occur. Guillain-Barré spectrum syndromes have been thought to be rare among solid organ transplant recipients. We describe an immunocompromised patient with a liver transplant who presented with ophthalmoplegia and bulbar deficits. His symptoms rapidly progressed to a state of descending paralysis involving the diaphragm; he then developed acute respiratory failure and eventually developed quadriparesis. Electromyography and a nerve conduction study demonstrated a severe sensorimotor axonal polyneuropathy consistent with Miller Fisher variant Guillain-Barré syndrome. Despite several negative nasopharyngeal swabs for COVID-19 polymerase chain reaction, a serology for SARS-CoV-2 IgG was positive. He was diagnosed with Miller Fisher-Guillain-Barré overlap syndrome with rapid recovery following treatment with plasma exchange. Although Guillain-Barré is a rare complication in solid organ transplant recipients, this case highlights the importance of rapid diagnosis and treatment of neurologic complications in transplant patients. Furthermore, it demonstrates a possible case of neurological complications from COVID-19 infection

Ransomware Cyberattack Associated With Cardiac Arrest Incidence and Outcomes at Untargeted, Adjacent Hospitals.

OBJECTIVES: Healthcare ransomware cyberattacks have been associated with major regional hospital disruptions, but data reporting patient-oriented outcomes in critical conditions such as cardiac arrest (CA) are limited. This study examined the CA incidence and outcomes of untargeted hospitals adjacent to a ransomware-infected healthcare delivery organization (HDO). DESIGN SETTING AND PATIENTS: This cohort study compared the CA incidence and outcomes of two untargeted academic hospitals adjacent to an HDO under a ransomware cyberattack during the pre-attack (April 3-30, 2021), attack (May 1-28, 2021), and post-attack (May 29, 2021-June 25, 2021) phases. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Emergency department and hospital mean daily census, number of CAs, mean daily CA incidence per 1,000 admissions, return of spontaneous circulation, survival to discharge, and survival with favorable neurologic outcome were measured. The study evaluated 78 total CAs: 44 out-of-hospital CAs (OHCAs) and 34 in-hospital CAs. The number of total CAs increased from the pre-attack to attack phase (21 vs. 38; p = 0.03), followed by a decrease in the post-attack phase (38 vs. 19; p = 0.01). The number of total CAs exceeded the cyberattack month forecast (May 2021: 41 observed vs. 27 forecasted cases; 95% CI, 17.0-37.4). OHCA cases also exceeded the forecast (May 2021: 24 observed vs. 12 forecasted cases; 95% CI, 6.0-18.8). Survival with favorable neurologic outcome rates for all CAs decreased, driven by increases in OHCA mortality: survival with favorable neurologic rates for OHCAs decreased from the pre-attack phase to attack phase (40.0% vs. 4.5%; p = 0.02) followed by an increase in the post-attack phase (4.5% vs. 41.2%; p = 0.01). CONCLUSIONS: Untargeted hospitals adjacent to ransomware-infected HDOs may see worse outcomes for patients suffering from OHCA. These findings highlight the critical need for cybersecurity disaster planning and resiliency

Comparison of Mammography AI Algorithms with a Clinical Risk Model for 5-year Breast Cancer Risk Prediction: An Observational Study.

Background Although several clinical breast cancer risk models are used to guide screening and prevention, they have only moderate discrimination. Purpose To compare selected existing mammography artificial intelligence (AI) algorithms and the Breast Cancer Surveillance Consortium (BCSC) risk model for prediction of 5-year risk. Materials and Methods This retrospective case-cohort study included data in women with a negative screening mammographic examination (no visible evidence of cancer) in 2016, who were followed until 2021 at Kaiser Permanente Northern California. Women with prior breast cancer or a highly penetrant gene mutation were excluded. Of the 324 009 eligible women, a random subcohort was selected, regardless of cancer status, to which all additional patients with breast cancer were added. The index screening mammographic examination was used as input for five AI algorithms to generate continuous scores that were compared with the BCSC clinical risk score. Risk estimates for incident breast cancer 0 to 5 years after the initial mammographic examination were calculated using a time-dependent area under the receiver operating characteristic curve (AUC). Results The subcohort included 13 628 patients, of whom 193 had incident cancer. Incident cancers in eligible patients (additional 4391 of 324 009) were also included. For incident cancers at 0 to 5 years, the time-dependent AUC for BCSC was 0.61 (95% CI: 0.60, 0.62). AI algorithms had higher time-dependent AUCs than did BCSC, ranging from 0.63 to 0.67 (Bonferroni-adjusted P < .0016). Time-dependent AUCs for combined BCSC and AI models were slightly higher than AI alone (AI with BCSC time-dependent AUC range, 0.66-0.68; Bonferroni-adjusted P < .0016). Conclusion When using a negative screening examination, AI algorithms performed better than the BCSC risk model for predicting breast cancer risk at 0 to 5 years. Combined AI and BCSC models further improved prediction. © RSNA, 2023 Supplemental material is available for this article

A Comparison of Intubation and Airway Complications Between COVID-19 and Non-COVID-19 Critically Ill Subjects

Introduction The number of subjects infected with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the western hemisphere increased exponentially in the later months of 2020. With this increase in infection, the number of subjects requiring advanced ventilatory support increased concomitantly. We decided to compare the survival rates between coronavirus disease 2019 (COVID-19) subjects versus non-COVID-19 subjects undergoing intubation in the intensive care unit (ICU). We hypothesized that COVID-19 subjects would have lower rates of survival post-intubation. Methods We screened all subjects admitted to the adult critical care unit between January 2020 and June 2020 to determine if they met the inclusion criteria. These subjects were required to be spontaneously ventilating upon admission and eventually required intubation. Subjects were selected from our electronic health record (EHR) system EPIC© (Epic Systems, Verona, WI) through a retrospective ICU admission analysis. We identified and included 267 non-COVID-19 subjects and 56 COVID-19 subjects. Our primary outcome of interest was intubation-related mortality. We defined intubation mortality as unexpected death (within 48 hours of intubation). Our secondary outcomes were the length of stay in the ICU, length of time requiring ventilator support, and proportion of subjects requiring tracheostomy placement. Results Compared to non-coronavirus disease (COVID) subjects, COVID subjects were more likely to be intubated for acute respiratory distress. COVID subjects had longer stays in the ICU and longer ventilator duration than non-COVID subjects. COVID-positive subjects had a decreased hazard ratio for mortality (HR = 0.42, 95% CI: 0.20-0.87, P < 0.05) and increased chances of survival compared to non-COVID subjects. Conclusions We showed the rates of intubation survival were no different between the COVID and non-COVID groups. We attribute this finding to intubation preparation, a multidisciplinary team approach, and having the most experienced provider lead the intubation process

Phase II Single-Arm Study of Preoperative Letrozole for Estrogen Receptor-Positive Postmenopausal Ductal Carcinoma In Situ: CALGB 40903 (Alliance).

PurposePrimary endocrine therapy for ductal carcinoma in situ (DCIS) as a potential alternative to surgery has been understudied. This trial explored the feasibility of a short-term course of letrozole and sought to determine whether treatment results in measurable radiographic and biologic changes in estrogen receptor (ER)-positive DCIS.Patients and methodsA phase II single-arm multicenter cooperative-group trial was conducted in postmenopausal patients diagnosed with ER-positive DCIS without invasion. Patients were treated with letrozole 2.5 mg per day for 6 months before surgery. Breast magnetic resonance imaging (MRI) was obtained at baseline, 3 months, and 6 months. The primary end point was change in 6-month MRI enhancement volume compared with baseline.ResultsOverall, 79 patients were enrolled and 70 completed 6 months of letrozole. Of these, 67 patients had MRI data available for each timepoint. Baseline MRI volumes ranged from 0.004 to 26.3 cm3. Median reductions from baseline MRI volume (1.4 cm3) were 0.6 cm3 (61.0%) at 3 months (P < .001) and 0.8 cm3 (71.7%) at 6 months (P < .001). Consistent reductions were seen in median baseline ER H-score (228; median reduction, 15.0; P = .005), progesterone receptor H-score (15; median reduction, 85.0; P < .001), and Ki67 score (12%; median reduction, 6.3%; P = .007). Of the 59 patients who underwent surgery per study protocol, persistent DCIS remained in 50 patients (85%), invasive cancer was detected in six patients (10%), and no residual DCIS or invasive cancer was seen in nine patients (15%).ConclusionsIn a cohort of postmenopausal women with ER-positive DCIS, preoperative letrozole resulted in significant imaging and biomarker changes. These findings support future trials of extended endocrine therapy as primary nonoperative treatment of some DCIS