Indiana University-Purdue University Indianapolis (IUPUI) / Acute Myeloid Leukemia (AML) is the most common hematologic malignancy. Malglycemia is a disorder of glucose metabolism and includes hyperglycemia, hypoglycemia and the combination of hyperglycemia and hypoglycemia. Malglycemia has been shown to occur frequently during hospitalization among critical care patients and has been associated with increased risk of sepsis and mortality. Little is known, however, about the prevalence and role of malglycemia on the health outcomes of AML patients hospitalized for initial induction therapy. Malglycemia may be of particular importance to the patient with AML because, researchers have found that malglycemia may promote cellular changes which facilitate the progression of cancer, alter treatment response, and attenuate immune response. The purpose of this study was to determine the prevalence of malglycemia (hyperglycemia, hypoglycemia or the combination) and to examine its role on a comprehensive set of health outcomes (neutropenic days, infection, and septicemia, and sepsis, induction hospital length of stay, complete remission and mortality) in AML patients hospitalized for initial induction therapy. A retrospective cohort study design was used. Records of 103 AML patients, hospitalized for initial induction chemotherapy were reviewed. Results of the study showed that 98% of the AML patients had at least one episode of hyperglycemia, with a prevalence rate of 33% over the entire induction inpatient hospitalization for this population. All patients noted with hyperglycemia also had hypoglycemia and thus, the prevalence rate of hypoglycemia alone could not be determined. Prevalence of the combination of hyperglycemia and hypoglycemia was 1.4 %. Although not statistically significant, a trend was noted for AML patients with hyperglycemia to experience more days with neutropenia, greater numbers of infection, sepsis, septicemia and death (mortality) than patients without hyperglycemia during induction treatment. Patients with the combination of hyperglycemia and hypoglycemia also experienced an increased risk of developing septicemia (p = .025) and sepsis (p =.057). Future studies with larger sample sizes are needed to confirm these findings.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21680号 / 医博第4486号 / 新制||医||1036(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊佐 正, 教授 村井 俊哉, 教授 松原 和夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Ultrasound measurement of change in kidney volume is a sensitive indicator of severity of renal parenchymal injury. Am J Physiol Renal Physiol 319: F447–F457, 2020. First published July 20, 2020; doi:10.1152/ajprenal.00221.2020.—Noninvasive determination of the severity of parenchymal injury in acute kidney injury remains challenging. Edema is an early pathological process following injury, which may correlate with changes in kidney volume. The goal of the present study was to test the hypothesis that “increases in kidney volume measured in vivo using ultrasound correlate with the degree of renal parenchymal injury.” Ischemia-reperfusion (IR) of varying length was used to produce graded tissue injury. We first determined 1) whether regional kidney volume in rats varied with the severity (0, 15, 30, and 45 min) of warm bilateral IR and 2) whether this correlated with tubular injury score. We then determined whether these changes could be measured in vivo using three-dimensional ultrasound. Finally, we evaluated cumulative changes in kidney volume up to 14 days post-IR in rats to determine whether changes in renal volume were predictive of latent tubular injury following recovery of filtration. Experiments concluded that noninvasive ultrasound measurements of change in kidney volume over 2 wk are predictive of tubular injury following IR even in animals in which plasma creatinine was not elevated. We conclude that ultrasound measurements of volume are a sensitive, noninvasive marker of tissue injury in rats and that the use of three-dimensional ultrasound measurements may provide useful information regarding the timing, severity, and recovery from renal tissue injury in experimental studies.

No description available.

Enteral nutrition (EN) is often delayed in critically ill patients despite strong evidence to support that early enteral nutrition feeding is beneficial in this population. Adverse outcomes in critically ill patients in which nutrition is delayed include a longer length of stay and time on the ventilator, and a higher incidence of pneumonia and hospital mortality. The purpose of this literature review was to evaluate the current evidence regarding trophic enteral feeds in mechanically ventilated adult patients with acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and associated clinical outcomes. A retrospective literature review was performed to identify articles published on the topic of trophic feeds in mechanically ventilated adult patients with ALI/ARDS, with a focus on associated clinical outcomes. The studies included in this literature review indicated that the dose and timing of enteral nutrition in critically ill patients with ARDS/ALI had an effect on clinical outcomes. It is possible that additional variables such as the level of organ dysfunction and varying definitions for trophic enteral nutrition also influenced clinical outcomes. The United States (U.S.) and Canadian guidelines for nutrition supportrecommend either trophic or full EN for patients with ARDS/ALI on the basis that these two feeding strategies have similar patient outcomes over the first week of hospitalization. After reviewing the literature, we conclude that caution is warranted when following this recommendation. Regressions suggest full calorie enteral nutrition administered early in the course of critical illness significantly increased the odds of mortality, whereas full calorie enteral nutrition administered later reduced the odds of mortality.

Mild blast-induced traumatic brain injury (bTBI) is a modality of injury that has been of major concern considering a large number of military personnel exposed to the blast wave from explosives. bTBI results from the propagation of high-pressure static blast forces and their subsequent energy transmission within brain tissue. Current literature presents a neuro-centric approach to the role of mitochondria dynamics dysfunction in bTBI; however, changes in astrocyte-specific mitochondrial dynamics have not been characterized. As a result of fission and fusion, the mitochondrial structure is constantly altering shape to respond to physiological stimuli or stress insults by adapting structure and function, which are intimately connected. Dysregulation of the protein regulator of mitochondrial fission, DRP1, and upregulation in the phosphorylation of DRP1 at the serine 616 site is reported to play a crucial role in astrocytic mitochondrial dysfunction, favoring fission over fusion post-TBI. Astrocytic mitochondria are starting to be recognized to play an essential role in overall brain metabolism, synaptic transmission, and neuron protection. Mitochondria are vulnerable to injury insults leading to the worsening of mitochondrial fission and increased mitochondrial fragmentation. In this study, a combination of in vitro and in vivo bTBI models were used to examine the effect of blast on astrocytic mitochondrial dynamics. Acute differential remodeling of the astrocytic mitochondrial network was observed, accompanied by an acute (4hr) and sub-acute (7 days) activation of the GTP-protein DRP1. Further, results showed a time-dependent reactive astrocyte phenotype transition in the rat hippocampus. This discovery can lead to innovative therapeutics targets to help prevent secondary injury cascades that involve mitochondria dysfunction. / Doctor of Philosophy / Blast-induced traumatic brain injury (bTBI) is a modality of injury that has become prominent considering a large number of military personnel exposed to a blast wave caused by explosives. Blast injury results from the energy transmission of the blast wave to the brain. Within the brain, there are specialized cells, called astrocytes, that help maintain a healthy environment. This work investigates the role that astrocytes play during the injury recovery process. Within the astrocytes, there are organelles called mitochondria, that help maintain the energy for the cell. The number and function of mitochondria can change in response to the brain injury. They can increase in number by a process called fission and they can decrease in number by a process called fusion. These events effect the function of the mitochondria. Researchers have methods that can identify changes in the number and function of the mitochondria. In this work, astrocyte mitochondrial dynamics were examined and compared using models of bTBI. We found significant changes in the mitochondria of astrocytes, which could lead to an unhealthy environment in the brain. This discovery can lead to new treatments for patients that may improve their quality of life following bTBI.

No description available.

Introduction: An absolute majority of dental infections are treated without major complications. In exceptional situations dental infections can spread to surrounding structures such as the airways or even the brain leading to a life-threatening condition that requires hospitalization. According to literature, some qualified risk factors appear to be common in hospitalized patients. Aim: To outline factors typically seen in patients with acute maxillofacial infections with dental origin at Norrland University Hospital (NUS) and find possible association between these factors and the length of hospital stay.  Methods: A literature review using keywords associated with dental infections and acute throat and head infections was performed. Retrospective structured medical journal reviews of 58 patients suffering from acute maxillofacial infections which required hospitalization at NUS were analyzed. The results were analyzed using IBM SPSS Statistics software and Microsoft Office Excel. Results: The results indicated that overweight/obese people (Body Mass Index ⊵25) require longer care at the hospital due to their infection. Every other of the hospitalized patients had received dental treatment within 14 days prior to hospitalization.  Conclusions: In situations with acute maxillofacial infections of dental origin requiring hospitalization, BMI ⊵25 is eventually a risk factor. A group of patients received dental treatment for their infection, but the infection still exacerbated. How come? This requires deeper analysis with further studies.

BACKGROUND: Constipation is highly prevalent in older adults and may be associated with greater frequency of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We investigated the prevalence of lower defecation frequency (DF) and risk factors (including AECOPD) associated with lower DF among hospitalized elderly patients. METHODS: We conducted a retrospective case-control study in a community hospital of Southeast Ohio. Adults aged 65 years or older admitted during 2004 and 2006 were reviewed (N = 1288). Patients were excluded (N = 212) if their length of stay was less than 3 days, discharge diagnosis of Clostridium difficile-associated diarrhea, death or ventilator- dependent respiratory failure during hospitalization. Lower DF was defined as either an average DF of 0.33 or less per day or no defecation in the first three days of hospitalization; cases (N = 406) and controls (N = 670) were included for the final analysis. RESULTS: Approximately 38% had lower DF in this patient population. Fecal soiling/smearing of at least two episodes was documented in 7% of the patients. With the adjustment of confounders, AECOPD (adjusted odds ratio [AOR] =1.47, 95% confidence interval [CI] =1.01-2.13) and muscle relaxant use (AOR =2.94; 95% CI =1.29-6.69) were significantly associated with lower DF. Supplementation of potassium and antibiotic use prior to hospitalization was associated with lower risk of lower DF. CONCLUSIONS: Approximately 38% of hospitalized older adults had lower DF. AECOPD and use of muscle relaxant were significantly associated with lower DF; while supplementation of potassium and antibiotic use were protective for lower DF risk after adjusting for other variables.

Ischaemia/Reperfusion Injury (IRI) is the most common cause of acute kidney injury- a devastating clinical problem lacking any specific treatments to promote renal recovery. Macrophages (Mφ) are pleiotropic cells of the innate immune system, with roles spanning host defence, cytotoxicity, clearance of apoptotic cells and promotion of tissue repair. Mφ are also known to be important mediators of renal injury in other experimental models of renal disease including transplantation, obstruction and glomerulonephritis. This work sought to examine the role of Mφ in mediating renal IRI. Conditional renal Mφ and monocyte depletion prior to experimental IRI was achieved by administering diphtheria toxin to the CD11b-DTR transgenic animal. This had no impact on either renal function or structural injury. In contrast liposomal clodronate mediated Mφ depletion provided functional and structural protection from injury. Administration of exogenous apoptotic cells also protected renal function if delivered 24h prior to IRI. Immunodeficient SCID mice exhibited a protected injury phenotype after IRI, however derived no additional protection from the administration of either liposomal clodronate or i.v. apoptotic cells. These findings suggest that the protective phenotype must involve either lymphocyte populations or circulating antibody. Preliminary work demonstrates that SCID mice lack IgM natural antibody which deposits in the kidney in the first 30 minutes after IRI. It was also demonstrated that apoptotic cells bind IgM natural antibody present within the circulation. The potential for the key antioxidant enzyme Heme oxygenase-1 (HO-1) to protect renal function was also examined in aged mice using hemearginate (HA) - a potent HO-1 inducer. Echoing epidemiological studies in humans aged mice had increased susceptibility to IRI, whilst failing to induce medullary HO-1. The main site of medullary HO-1 induction by HA was in medullary Mφ, and the protective phenotype was abolished by Mφ ablation, implicating Mφ as the key mediators of HA induced protection in renal IRI. Final studies employed adenoviral transduction to overexpress HO-1 within bone marrow derived Mφ, leading to a modified phenotype with increased IL- 10 and phagocytosis, and reduced TNFα and NO production. When these were introduced in vivo after IRI renal function was improved, potentially due to accelerated clearance of renal platelet deposition.