Extensive Injury Research Articles

Quantitative MRI findings indicate diffuse white matter damage in Susac Syndrome.

BackgroundSusac Syndrome (SuS) is an autoimmune endotheliopathy impacting the brain, retina and cochlea that can clinically mimic multiple sclerosis (MS).ObjectiveTo evaluate non-lesional white matter demyelination changes in SuS compared to MS and healthy controls (HC) using quantitative MRI.Methods3T MRI including myelin water imaging and diffusion basis spectrum imaging were acquired for 7 SuS, 10 MS and 10 HC participants. Non-lesional white matter was analyzed in the corpus callosum (CC) and normal appearing white matter (NAWM). Groups were compared using ANCOVA with Tukey correction.ResultsSuS CC myelin water fraction (mean 0.092) was lower than MS(0.11, p = 0.01) and HC(0.11, p = 0.04). Another myelin marker, radial diffusivity, was increased in SuS CC(0.27μm2/ms) compared to HC(0.21μm2/ms, p = 0.008) and MS(0.23μm2/ms, p = 0.05). Fractional anisotropy was lower in SuS CC(0.82) than HC(0.86, p = 0.04). Fiber fraction (reflecting axons) did not differ from HC or MS. In NAWM, radial diffusivity and apparent diffusion coefficient were significantly increased in SuS compared to HC(p < 0.001 for both measures) and MS(p = 0.003, p < 0.001 respectively).ConclusionsOur results provided evidence of myelin damage in SuS, particularly in the CC, and more extensive microstructural injury in NAWM, supporting the hypothesis that there are widespread microstructural changes in SuS syndrome including diffuse demyelination.

Extensive Traumatic Anterior Chest Wall Injury Including Type I Manubriosternal Dislocation

Extensive Traumatic Anterior Chest Wall Injury Including Type I Manubriosternal Dislocation

Placebo-controlled trial of oral amantadine and zolpidem efficacy on the outcome of patients with acute severe traumatic brain injury and diffuse axonal injury.

Background:A constituent of diffuse axonal injury (DAI) is supposed to be present in about 1/3 of all severe traumatic brain injury (TBI) as specified by pathologic documents. Diffuse axonal injury is categorized by extensive injury to axons in the brain. A rise in the incidences of TBI, and the limited study to verified effect of drugs like amantadine and zolpidem in improving the consciousness levels of patients with acute traumatic brain injury with axonal injury enthused us to initiate this study in the acute TBI patients.Methods:In our randomized, controlled trial involving patients with acute severe TBI, we studied 66 patients in 3 groups. Group 1 (n=22) received oral amantadine, Group 2 (n=22) received oral zolpidem, whereas group 3 (n=22) received placebo, the first 8 days after injury respectively. The primary outcome measures included GCS (Glashow coma scale) through the initial admission, a complete medical history was recorded, and each patient had a meticulous physical and neurological investigation.Results:We found that the administration of amantadine in an acute phase after injury improved the rate of patients GCS and GOS (Glasgow Outcome Scale) compared with zolpidem and placebo groups, but without any significant statistical difference.Conclusion:Our results has emphasized that because amantadine has intense biochemical effects on several ways, it appears to be beneficial in acute period after DAI-associated TBI.

Aortomesenteric Dissection as a Rare Cause of Ischemic Cholangiopathy: Clinical Impact of Right Replaced Hepatic Artery

Background: Ischemic cholangiopathy (IC) is a focal or extensive injury of the bile ducts due to impaired blood supply. The etiologies of this entity are liver transplantation (LT), transarterial chemotherapy and chemoembolization, among others. Patients usually present with recurrent episodes of jaundice, fever, biliary pain or itching. We present a rare case of ischemic cholangipathy of the right hepatic lobe, secondary to aortic dissection.

Explaining the challenges of hospitals admitting COVID-19 patients from the perspective of managers (a qualitative study).

Crises are often unavoidable events that occur around the world. Hospitals play an important role in treating patients and preventing extensive injuries in times of crisis, requiring adequate preparedness. In order to design a proper planning system, it is essential to be aware of the challenges of hospitals during a crisis. The purpose of this study was to explain the challenges of hospitals admitting COVID-19 patients in the city of Mashhad, Iran, from the perspective of their managers. This study employed a qualitative approach, using the method of conventional content analysis and was conducted from May to July 2020. A purposive sampling method was used to recruit the senior managers of hospitals admitting COVID-19 patients in Mashhad. The interviews were conducted face to face, with open-ended questions following an interview guide based on semi-structured questions, and continued until data saturation was reached. Data were analyzed using Atlas Ti software. After the implementation of the interviews, first 665 initial codes were extracted from the data, and after removing the overlapping sequences, a total of 115 codes were obtained. Three categories (organizational challenges, extra organizational challenges, and challenges related to information domain), 13 sub-categories, and 33 codes were extracted from the content analysis of the interviews. The main themes propounded in the field of challenges of COVID-19 referral hospitals in Mashhad were organizational challenges, extra organizational challenges, and information domain challenges. The results of this study showed that the hospitals admitting COVID-19 patients in Mashhad faced many challenges. To improve the quality of services in postcrisis phase, replacing hospitals' equipment, revising curriculums at medical universities, staff retraining, recruiting skilled human resources, and creating a supportive community context are necessary. For sure, the COVID-19 crisis will not be the last one, we have to be prepared for the bigger health crisis.

Holistic Approach via Physiotherapeutic Intervention in a Complex Multiple Fracture Hampering a Middle-Class Man’s Life- a Case Report

Ankle fractures contribute to almost nine percent of all fractures of the weight-bearing joints, with uni, bi, and trimalleolar fractures being the most prevalent. Weber’s and (AO/ASIF) classifications are commonly used for easy analysis. Tibial plateau fractures can range in severity from stable to severely comminuted unstable fractures with extensive tissue injury, putting the extremities' at risk, according to the Schatzker grading system. The ulna is a long bone in the forearm that extends parallel to the radius and travels medially. The severity of proximal ulna fractures ranges from basic AO/OTA Classification fractures to severe Monteggia fractures or Monteggia-like lesions. After a road accident, a 35-year-old man with compound grade 3B ankle dislocation, Schatzker type 1 fracture of tibia, and proximal 1/3 ulnar shaft fracture of the left side were diagnosed on x-ray with external application of a delta fixator over the ankle, open reduction and internal fixation on the tibial plateau with screws and the nail was impacted over the ulna fracture. After the procedure, the patient was treated with physical therapy for 12 weeks, beginning with static regimens and proceeding to dynamic exercises, electrotherapeutic modalities, strengthening exercises, and gait exercises. The purpose of this study was to explore potential favorable rehabilitation effects in the use of exercises following operatively treated unstable ankle fractures requiring partial weight-bearing in the first six postoperative weeks.&#x0D; Conclusion: It could be shown that Immediate Postoperative Physical Therapy protocol in a proper scheduled manner helped the Patient to return to his daily activities with improved ranges, strength, and motivation to work again without any difficulties.

Traumatic Lower Extremity Vascular Injuries and Limb Salvage in a Civilian Urban Trauma Center

Data on management of traumatic lower extreity arterial injuries comes largely from military experience and involves few civilian centers. This study reports on the experience of an urban trauma center and factors associated with limb loss. A retrospective review of lower extremity arterial injuries between 2013 and 2020 at an academic urban level 1 trauma center was completed. Patients with lower extremity revascularization were included in the final data analysis. Demographics, clinical variables, operative details, type of revascularization, as well as 30-day morbidity and postoperative outcomes were analyzed. The primary outcome of interest was 30-day limb loss. Secondary outcomes included postoperative complications and functional outcomes. Seventy-five patients were included in our analysis. Sixty-nine were male (92%), mean age 33 ± 15 years, 50 patients had penetrating trauma (67%), mean injury severity score was 15 ± 9. Thirty-day limb loss was reported in 8 (11%). Factors associated with limb loss included female sex (P=0.001), high body mass index (P=0.001), blunt injury (P=0.001), associated fractures (P=0.005), significant soft tissue injury (P=0.007), delayed repair after shunt placement (P=0.003), bypass revascularization (P=0.001), initial revascularization failure (P=0.019), and wound complications (P < 0.001). Fifty-five patients had at least one return to the operating room (ROR), including 24 patients (32%) for complications related to their revascularization. These included delayed compartment syndrome (n=7), revascularization failure (n=9), bleeding (n=3), and vascular surgical wound complications (n=5). Mean length of hospital stay (LOS) for the cohort was 24 ± 20 days with 3 ± 3 ROR, in contrast patients who ultimately required amputation had LOS of 57 ± 21 days with 8 ± 4 ROR. Fifty-seven patients (76%) followed in clinic for a median 36 [14-110] days, with only 32 (43%) at >30 days. Twenty-three reported ambulation without assistance, 9 neuromotor deficit including 1 patient that had delayed amputation. Patients with blunt trauma and associated fracture and/or extensive soft tissue injury are at risk of limb loss. These injuries are often associated with postoperative wound complications, requiring aggressive soft tissue care that substantially increases ROR and LOS; Expectations for limb salvage in these patients should be tempered when the other associated factors with limb loss mentioned above are also present. When limb salvage is achieved, regaining full limb function remains a challenge.

Fractional CO2 laser therapy of hypertrophic scars - evaluation of efficacy and treatment protocol optimization.

Hypertrophic scars are an unwanted and mutilating consequence of deep burns, and are further exacerbated by extensive burn injuries. Fractional CO2 laser therapy is one of the methods for complex treatment of hypertrophic scars, it has been used since 2007 [1]. Although its effectiveness has been objectively proven in clinical practice, the optimal settings parameters have not been determined. To evaluate the effect of laser therapy, previously designed evaluation tools are used, which evaluate the quality of scars well, but fail to capture specific changes for the performed laser therapy. Fractional CO2 laser therapy of hypertrophic scars is performed at the Department of Plastic and Esthetic Surgery, University Hospital Olomouc, since 2017 and the systematic study took place in 2019-2020. In common, 25 hypertrophic scars were treated in 13 patients; each scar was treated by fractional CO2 laser therapy more than once. Statistical analysis detected statistically significant improvement of the texture of the scars and the improvement of overall functional and esthetic result. We found significant reduction of the height under 2 mm (62,5% of scars) in scars with the height &gt; 2 mm before the initiation of laser therapy. Correlation analysis detected astatistically significant positive correlation between the energy of laser beam and the reduction volume of the scar protruding above the niveau of healthy surrounding tissue. Fractional CO2 laser therapy showed statistically significant efficacy in the reduction of the risks associated with full-format CO2 laser-therapy. Fractional treatment was very well tolerated by the patients. Topical 5% lidocaine gel was effective in 24 out of 25 patients. Further healing was without complications in all patients. Fractional CO2 laser therapy has achieved statistically significant improvement of the texture and reduction of hypertrophic scars and overall improvement of functional and esthetic result in our study.

Pre-Hospital and In-Hospital Management of an Abdominal Impalement Injury Caused by a Tree Branch

In South Korea, most patients who visit trauma centers with abdominal injuries have blunt trauma, and penetrating injuries are relatively rare. In extremely rare cases, some patients are admitted with a long object penetrating their abdomen, and these injuries are referred to as abdominal impalement injuries. Most cases of impalement injuries lead to fatal bleeding, and patients often die at the scene of the accident. However, patients who survive until reaching the hospital can have a good prognosis with optimal treatment. A 68-year-old female patient was admitted to the trauma center with a 4-cm-thick tree branch impaling her abdomen. The patient was transported by a medical helicopter and had stable vital signs at admission. The branch sticking out of the abdomen was quite long; thus, we carefully cut the branch with an electric saw to perform computed tomography (CT). CT revealed no signs of major blood vessel injury, but intestinal perforation was observed. During laparotomy, the tree branch was removed after confirming that there were no vascular injuries, and enterostomy was performed because of extensive intestinal injury. After treating other injuries, the patient was discharged without any complications except colostomy. Abdominal impalement injuries are treated using various approaches depending on the injury mechanism and injured region. However, the most important consideration is that the impaled object should not be removed during transportation and resuscitation. Instead, it should only be removed after checking for injuries to blood vessels during laparotomy in an environment where injury control is possible.

Gender differences in ECG markers of increased risk for malignant arrhythmias, peripheral blood parameters, and adverse outcomes in patients with COVID-19 pneumonia

Background: The available data on gender differences in a) markers of cardiac involvement, b) peripheral blood parameters, and c) clinical adverse outcomes related to COVID-19 pneumonia severity are limited in the literature.: Objectives: To investigate gender differences in ECG markers of increased risk for malignant arrhythmias. This includes T from peak to end (Tp-e) interval, corrected QT (QTc), transmural dispersion of repolarization (TDR)(Tp-e/QTc), and index of cardiac electrophysiological balance (iCEB)(QTc/QRS), peripheral blood parameters, and in-hospital adverse outcomes in patients with COVID-19 pneumonia. Methods: A cross sectional study enrolled patients with COVID-19 pneumonia admitted to hospital from August 20th, to September 30th, 2020. Results: A total of 197 patients were included. Ninety-six (47%) were men and 101 women. There were no significant gender related differences concerning comorbidities. Men had higher QRS values, Tp-e interval and TDR, and lower values of iCEB. No significant gender differences were observed in the distribution of QTc interval. Men stayed longer in the hospital and had more extensive lung injury than women. In men, prolonged QTc interval, low lymphocytes %, high platelet distribution width (PDW), and low hemoglobin (Hb) were the main predictors of adverse in-hospital outcome, while prolonged QTc interval, high PDW, and low platelet count were the main predictors of adverse in-hospital outcome for women. Conclusions: Men had higher TDR values, lower iCEB, stayed longer in the hospital, and had more extensive lung injury than women, suggesting that, despite that there was no significant difference in mortality incidents between the two genders, the difference in surrogate markers may indicate that men are at a higher risk for adverse outcomes.

Abstract 12356: Prevalence and Patterns of Injury Detected by Head-to-Pelvis Sudden Death Computed Tomography Following Cardiopulmonary Resuscitation

Introduction: Patients resuscitated from out-of-hospital cardiac arrest (OHCA) frequently have skeletal and visceral injuries identifiable by computed tomography, although the prevalence, types of injury, and potential effects on clinical outcomes are poorly characterized. Methods: We assessed the prevalence of resuscitation-attributable injury in a prospective, observational diagnostic utility study of a head-to-pelvis sudden death computed tomography (SDCT) protocol after successful resuscitation from OHCA. SDCT was performed within six hours of arrival at two academic medical centers. CT data were independently analyzed by two blinded radiologists. Primary outcomes included total injuries and time-critical injuries (such as organ laceration). Exploratory outcomes were clinical associations with injury and survival to discharge. Results: Among 104 patients with OHCA (mean age 56 ± 15 years, 31% female), 59% of events were witnessed and 60% had bystander CPR. Initial rhythms were pulseless electrical activity (38%), ventricular tachycardia/fibrillation (29%), and asystole/unknown (33%). Mean CPR time was 15.4 ± 10.6 minutes; mechanical chest compression systems were used in 27% of cases. The prevalence of injury was high (80%; Table), including 19 patients (18%) with time-critical findings. Compared to patients without injury, patients with injury had numerically lower BMI (24.2 ± 7.7 vs. 26.7 ± 8.0), higher use of mechanical CPR (29% vs. 19%), longer CPR time (16.1 ± 11.0 vs. 12.3 ± 8.5 min), and lower survival to discharge (40% vs. 52%), although none were significant (p= NS for all). Conclusion: In patients resuscitated from OHCA, head-to-pelvis SDCT identified injury in most patients, with nearly one in five with time-critical findings and nearly one half with extensive ribcage injuries that may affect ventilation. These data suggest that SDCT has additional diagnostic utility and treatment implications beyond evaluating causes of OHCA.

PPRP and LPRP regenerative effect in 3D muscle injury celular model

Introduction: Extensive muscle injuries are a clinical challenge due to the formation of fibrous tissue that can lead to chronic pain and disability. Therefore, the search for alternative treatments to regenerate the injured muscle is mandatory. Platelet-Rich-Plasma is an autologous blood derivative in which platelet concentration is above peripheral blood levels. Platelets secrete growth factors and signalizing molecules and even though it is already used in clinical practice for tissue regeneration with positive outcomes, there are no concrete evidence of its efficacy on muscle tissue. The goal of this study was to evaluate the effects of PPRP (poor in leukocytes) and LPRP (rich in leukocytes) in 3D C2C12 muscle cell cultures, after injury with Cardiotoxin (CTX) and BaCl2. Methodology: On day 0 spheroids were prepared using scaffold-free technology in agarose micro-molds. Injury was induced two days later by adding CTX (1uM) or BaCl2 (0.7%). Murine PPRP and LPRP were added on day 4 and on day 6 the spheroids were collected for analysis. The volumes were calculated using brightfield images, and their viability was quantified by calcein/7AAD staining. Results: The spheroids were observed for 16 days. Regarding the spheroid volume, we could observe an exponential growth curve, reaching a plateau by day 12. On day 1, the volume was de 2,6x107 ± 3,83x106 um3 and on the last day, 8,68x107 ± 3,72x107 um3.The necrotic center volume was 5,96x106 ± 2,24x106 um3 on day one e presented a reduction tendency by the fourth day. The total spheroid volume was 2.7 X larger than the necrotic center volume after a week of growth (p&lt;0.05), and 22X larger after 15 days (p&lt;0.01). After characterization, the spheroid injury was standardized by adding com CTX 1uM, BaCl2 (1.4%) 50%, 12.5%, e 6.25% in volume, for 48 hours. Afterwards, injury was induced with com BaCl2 0.7% or CTX 1uM, followed by PRP treatments. BaCl2 injury led to 60.5% reduction in spheroid volume (p&lt;0.001), and 54% reduction in its viability when compared to control group (p&lt;0.05). There was no statistic difference between CTX spheroids volume and control group volumes, but CTX reduced viability in 80% (p&lt;0.0001). In groups injured with BaCl2, LPRP treatment increased spheroid volume in 70% (p&lt;0.05). However, there was no statistically significant increase in viability with PRP treatment. In Groups injured with CTX, treatment with PPRP increased viability in 50% and LPRP treated groups were 10X larger than CTX alone (p&lt;0,0001), and 4X larger than the group treated with PPRP (p&lt;0.05). Conclusion: Our data shows for the first time the characterization of a 3D muscle injury model, and the effects of PRP in viability increase and positive influence on the spheroid’s growth. Though preliminary, these results may have great relevance for future therapy studies and reducing animal model use.

L-theanine relieves acute alcoholic liver injury by regulating the TNF-α/NF-κB signaling pathway in C57BL/6J mice

Acute alcoholic liver injury (AALI) refers to the inflammatory hepatic damage caused by alcohol. In severe cases, it can lead to steatohepatitis, alcoholic fibrosis and even cirrhosis. In this study, we analyzed the hepatoprotective activity of L-theanine on mice fed with a large amount of ethanol at one time, and the underlying molecular mechanism. The extensive liver injury caused by alcohol feeding was alleviated by L-theanine, which reduced tissue damage, decreased transaminase levels, and increased antioxidant activity. Mechanistically, L-theanine downregulated phosphorylated NF-κB, TNF-α and IKKα in the liver tissues and the LO2 normal hepatocyte cell line, which in turn lowered secretion of iNOS, IL-1β and IL-6. Taken together, L-theanine prevents alcohol-induced liver inflammation by blocking the intrahepatic TNF-α/NF-κB pathway, and is a promising treatment strategy against AALI.

2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients: Executive Summary.

2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients: Executive Summary.

Neuroplasticity Mechanisms and Prospects for Personalized Rehabilitation Strategies in Patients with Motor and Cognitive Impairments

Aim. To highlight the most important areas of research on the problems of rehabilitation after stroke and the prospects for the development of new rehabilitation strategies, taking into account individual characteristics. Neuroplastic outcomes of anemic infarctions are presented by multi-pattern positive processes of synaptogenesis, sprouting, synthesis of neuroprotective proteins, and destructive effects of stress plasticity inducing dystonic disturbances, deterioration of stabilometric parameters and locomotor gait mechanisms with support deterioration [1]. Thus, specialists in neurorehabilitation should know the basics of fundamental neurophysiological processes in the central nervous system, interhemispheric networks of the brain, and optimize rehabilitation programs, taking into account individualized recovery profiles [2]. One of the factors influencing recovery after a stroke is nervous reorganization, which is proportional to the amount of damage [3]. The processes of neuroplasticity are studied from the standpoint of returning to the pre-stroke recovery model (with minor injuries) – forming “optimal” plasticity and compensatory strategies of “destructive” plasticity (with extensive hemispheric injuries). Micro-RNA (miRNA) are understudied in the neuroprotective reaction to cerebral ischemia. Another important modulator of stroke outcomes is the brain-derived neurotrophic factor (BDNF). Processing of the defective BDNF synthesis when the amino acid valine is replaced by methionine (val-met) that occurs during allelic disorders is of outstanding interest. Conclusion. Promising research areas for strategic approaches to rehabilitation after a stroke are the study of hemispheric introduction, miRNA and neuroprotection cascades; BDNF as an inducer of neuronal differentiation. Allelic BDNF polymorphisms induce lower recovery potential after stroke. Under certain environmental conditions motor learning can overcome the neuroplasticity deficit in the BDNF gene polymorphism. The studies have shown general patterns of positive effects of aerobic stimuli with enhanced BDNF secretion in the recovery of patients with cognitive and motor impairments; nevertheless, the onset period, intensity, duration and exercises rhythmicity have not been established in cerebral stroke. Future studies are likely to optimize rehabilitation profiles based on genetic characteristics.

Hepatic susceptibility to oxidative damage after repeated concomitant exposure to aspartame and aflatoxin B1 in rats

The potential interactions among food additives/contaminants and the consequences to biological systems is a topic that is rarely addressed in scientific literature. Thus, the current study investigated if the combined administration of ASP and AFB1 would impair hepatic and renal oxidative status. Male Wistar rats received during 14 days once a day ASP (75 mg/Kg) and/or AFB1 (250 µg/Kg) through intragastric route. At the end of experimental protocol, samples of liver and kidneys were collected for assessing biochemical markers of oxidative status. In the hepatic tissue, the treatment with a single substance (ASP or AFB1) caused an increase in TBARS levels, and a reduction in non-enzymatic antioxidant defenses (Vit C and NPSH levels and FRAP test). In the kidneys, TBARS levels were increased only in the group that received ASP + AFB1. The association reduced NPSH content, while the treatment with AFB1 reduced the FRAP levels. GST and CAT activities were increased in all treatments. Overall, ASP and AFB1 association presented higher toxic effects to the tissues. To the best of our knowledge, this is the first study demonstrating that the associated use of both ASP and AFB1 induces more extensive injuries in comparison to the effects caused by each one alone. Therefore, these data demonstrated that concomitant exposure to ASP and AFB1 potentiated their oxidative damage in hepatic tissue, suggesting that this organ is particularly sensitive to the toxic action induced by these substances.

Secondary sclerosing cholangitis: a lesser known side effect of pembrolizumab therapy

Abstract Introduction/Objective Immune check-point inhibitors have increasingly taken hold as mainstays of various cancer treatments, revolutionizing outcomes for individuals diagnosed with terminal malignancy. Hepatotoxicity is reported to occur in 2-10% patients, predominantly manifesting as a mixed cholestatic hepatitis pattern of injury. Cholangitis is a rare immune-mediated adverse event (irAE). We present a case of pembrolizumab-induced secondary sclerosing cholangitis presenting with multiple biliary strictures. Early recognition is crucial as these cases are resistant to treatment with steroids. Methods/Case Report 82-year-old woman with recurrent, metastatic, high grade urothelial carcinoma status post cystectomy and neoadjuvant chemotherapy, presented with new onset obstructive jaundice (alkaline phosphatase 958 U/L, aspartate aminotransferase of 331 U/L, alanine aminotransferase of 422 U/L, and total bilirubin of 19.8 mg/dL) following two weeks of pembrolizumab therapy. MRCP suggested intrahepatic biliary ductal dilation. ERCP showed multiple strictures involving hepatic bifurcation, left, right and intrahepatic ducts with beaded intrahepatic bile ducts. Liver biopsy showed expanded portal tracts with mixed inflammatory infiltrate, extensive bile duct injury, neutrophilic cholangitis, ductular proliferation, and perivenular cholestasis (10% dropout) concerning for mechanical obstruction. CK7 did not show ductopenia and immunostain IgG4 was negative. All autoimmune work-up was negative. Liver enzymes continued to rise despite multiple therapeutic stents, drains, high-dose corticosteroids, ursodiol and mycophenolate mofetil. The patient died five months later. Results (if a Case Study enter NA) NA Conclusion Pemrolizumab-induced secondary sclerosing cholangitis is a rare, hence under-recognized, adverse effect of check point inhibitor-mediated hepatotoxicity. It is important to recognize this association, as it has limited benefit from steroid therapy. Our finding of pembrolizumab-related SC adds to the growing body of literature of immune check-point inhibitor-related hepatobiliary injury and calls for further characterization of PD-1/PD-L1 inhibitor SC and its clinical implications.

Isolated jejunal necrosis following corrosive acid poisoning

Corrosive acid poisoning is common in Asian countries, and most of the time, it is of suicidal intent in adults. Commonly they lead to extensive injuries of the upper gastrointestinal tract, and isolated involvement of the lower gastrointestinal tract is rare. We present a 35-year-old male who presented to us with a history of corrosive acid ingestion mixed with alcohol. Imaging did not demonstrate any pneumoperitoneum. The patient underwent exploratory laparotomy and found to have isolated jejunal necrosis without any evidence of injury to the stomach and duodenum. Segmental resection and end-to-end anastomosis were done.

Immunometabolic Therapeutic Targets of Graft-versus-Host Disease (GvHD).

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option in the treatment of aggressive malignant and non-malignant blood disorders. However, the benefits of allo-HSCT can be compromised by graft-versus-host disease (GvHD), a prevalent and morbid complication of allo-HSCT. GvHD occurs when donor immune cells mount an alloreactive response against host antigens due to histocompatibility differences between the donor and host, which may result in extensive tissue injury. The reprogramming of cellular metabolism is a feature of GvHD that is associated with the differentiation of donor CD4+ cells into the pathogenic Th1 and Th17 subsets along with the dysfunction of the immune-suppressive protective T regulatory cells (Tregs). The activation of glycolysis and glutaminolysis with concomitant changes in fatty acid oxidation metabolism fuel the anabolic activities of the proliferative alloreactive microenvironment characteristic of GvHD. Thus, metabolic therapies such as glycolytic enzyme inhibitors and fatty acid metabolism modulators are a promising therapeutic strategy for GvHD. We comprehensively review the role of cellular metabolism in GvHD pathogenesis, identify candidate therapeutic targets, and describe potential strategies for augmenting immunometabolism to ameliorate GvHD.

Triggers for the Nrf2/ARE Signaling Pathway and Its Nutritional Regulation: Potential Therapeutic Applications of Ulcerative Colitis.

Ulcerative colitis (UC), which affects millions of people worldwide, is characterized by extensive colonic injury involving mucosal and submucosal layers of the colon. Nuclear factor E2-related factor 2 (Nrf2) plays a critical role in cellular protection against oxidant-induced stress. Antioxidant response element (ARE) is the binding site recognized by Nrf2 and leads to the expression of phase II detoxifying enzymes and antioxidant proteins. The Nrf2/ARE system is a key factor for preventing and resolving tissue injury and inflammation in disease conditions such as UC. Researchers have proposed that both Keap1-dependent and Keap1-independent cascades contribute positive effects on activation of the Nrf2/ARE pathway. In this review, we summarize the present knowledge on mechanisms controlling the activation process. We will further review nutritional compounds that can modulate activation of the Nrf2/ARE pathway and may be used as potential therapeutic application of UC. These comprehensive data will help us to better understand the Nrf2/ARE signaling pathway and promote its effective application in response to common diseases induced by oxidative stress and inflammation.