Stomal varices are a rare phenomenon that can infrequently develop in patients with enterostomies and portal hypertension. Acute gastrointestinal bleeding from stomal varices can be life threatening and is often a diagnostic challenge. We present a case of severe gastrointestinal hemorrhage from stomal varices requiring emergent intervention with transjugular intrahepatic portosystemic shunt (TIPS) and plug embolization. A 61 year old male patient with a history of colorectal adenocarcinoma status post chemotherapy, radiation, along with low anterior colon resection with ostomy creation presented with a one day history of sudden onset of bright red blood from his colostomy site. He had a known history of decompensated cirrhosis related to hepatitis C and alcohol abuse. On arrival, the patient was tachycardic with borderline low blood pressure with evidence of bright red bleeding from his ostomy site. After initial resuscitation, a colonoscopy through the stoma revealed active bleeding from what appeared to be submucosal colonic varices. The patient continued to experience large volumes of blood loss and became more hemodynamically unstable. Cross sectional imaging showed colonic varices being fed by a branch of the inferior mesenteric vein. The patient underwent TIPS followed by Amplatzer plug embolization of the branch of the interior mesenteric vein that was feeding the colonic stomal varices. The patient’s bleeding was stopped by the combination of these therapeutic modalities and he recovered without complication. The current standard of care for treatment of such varices is with either (1) local therapy with ligation or sclerotherapy, (2) surgical interventions such as stomal manipulation or vessel shunting, either transhepatic or portosystemic to reduce portal pressures, or (3) liver transplantation. Our patient required an unusual combination of TIPS and Amplatzer plug embolization to control his massive hemorrhage. This combination of therapies has been shown effective for the management of select cases of esophageal or gastric variceal bleeding; however, our case demonstrates that the application of the TIPS plus Amplatzer plug embolization can be applied more broadly to the rare scenario of colonic stomal varices.

abstract: Intracerebral hemorrhage (ICH) is a devastating type of acute brain injury with high mortality and disability. Acute brain injury swiftly alters the immune reactivity within and outside the brain; however, the mechanisms and influence on neurological outcome remains largely unknown. My dissertation investigated how ICH triggers focal and systemic immune responses and their impact hemorrhagic brain injury. At the focal level, a significant upregulation of interleukin (IL)-15 was identified in astrocytes of brain sections from ICH patients. A transgenic mouse line where the astrocytic IL-15 expression is controlled by a glial fibrillary acidic protein promoter (GFAP-IL-15tg) was generated to investigate its role in ICH. Astrocyte-targeted expression of IL-15 exacerbated brain edema and neurological deficits following ICH. Aggravated ICH injury was accompanied by an accumulation of pro-inflammatory microglia proximal to astrocytes in perihematomal tissues, microglial depletion attenuated the augmented ICH injury in GFAP-IL-15tg mice. These findings suggest that IL-15 mediates the crosstalk between astrocytes and microglia, which worsens ICH injury.Systemic immune response was investigated by leveraging the novel method of obtaining and analyzing bone marrow cells from the cranial bone flaps of ICH patients. A swift increase of hematopoietic stem cell (HSCs) population in the bone marrow was identified, along with a shift towards the myeloid cell lineage. Human findings were mirrored in an ICH mouse model. Fate mapping these HSCs revealed increased genesis of Ly6Clow monocytes in the bone marrow, which transmigrate into the hemorrhagic brain and give rise to alternative activation marker bearing macrophage. Blockade of the β3-adrenergic receptor or inhibition of Cdc42 abolished ICH-induced myeloid bias of HSCs. Importantly, mirabegron, a Food and Drug Administration-approved β3 adrenergic receptor agonist, and a Cdc42 activator, IL-3, enhanced bone marrow generation of Ly6Clow monocytes and improved recovery. These results suggest that brain injury modulates HSC lineage destination to curb distal brain inflammation, implicating the bone marrow as a unique niche for self-protective neuroimmune interactions. Together, these results demonstrate how acute brain injury exerts a profound yet distinct effect on immune responses within and outside the brain and sheds new light on neuroimmune interactions with potential clinical implications. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2020

Viele Studien haben sich bereits mit Nutzen und Risiken einer intensivierten Insulintherapie (IIT) intensivmedizinischer Patienten auseinandergesetzt. Die unterschiedlichen Ergebnisse gaben Anlass, die Auswirkungen einer Hyperglykämie auf Patienten mit einer Subarachnoidalblutung (SAB) weiter zu analysieren. In diesem Zusammenhang war der Stellenwert einer IIT von besonderem Interesse. Um den Einfluss des erhöhten Blutzuckers möglichst genau zu erfassen, wurde mittels Integralfunktion die Blutzuckerhöhe in Abhängigkeit der Zeit bestimmt. Es konnte ein negativer Einfluss einer hyperglykämen Stoffwechsellage auf den Krankheitsverlauf der Patienten dargestellt werden. Hervorzuheben sind hier vor allem Patienten, die sich initial in einem besseren Zustand befanden. Anschließend erfolgte die Einführung einer intensivierten Insulintherapie. In der IIT war es nicht immer möglich, den gewünschten Zielbereich des Blutzuckers zu erreichen, um einen signifikanten Unterschied beider Therapiegruppen bezüglich der Blutzuckereinstellung zu erhalten. Dennoch zeigte sich ein deutlicher Trend zugunsten der intensiviert therapierten Gruppe und dessen Krankheitsverlauf. Die Behandlung der Hyperglykämie durch eine IIT bleibt ein wichtiger Aspekt in der Intensivmedizin. Anzustreben ist eine moderate Insulintherapie, damit sowohl Hypo- als auch Hyperglykämien weitestgehend verhindert und so das Genesungspotential der Patienten unterstützt werden kann.

Postpartum hemorrhage (PPH) is the leading direct cause of maternal mortality worldwide, with the majority of deaths taking place in the least developed countries of the world. Low- and middle-income countries (LMICs) have increased rates of PPH due to lack of access to healthcare, inadequate number of care providers and availability of interventions and resources needed. PPH has four main etiologies: uterine atony, trauma, retained placenta and coagulopathy. The most common and challenging to treat is uterine atony, where a lack of uterine contractility leads to massive hemorrhage postpartum. Specific risk factors have been identified that increase a woman’s risk of developing PPH. Risk factors of PPH can be categorized as biological, demographical and social risk factors. Many people in LMICs experience a lot of the social risk factors like lack of providers, skilled facilities and resources available to them in case of an obstetric emergency. Home births are also a common practice in many LMICs, placing a woman further from any resources she may have had access to if she was at a health facility. PPH can also occur in women without risk factors and requires that providers always be prepared to treat it. Interventions to treat PPH are well known and encompass both pharmacological and non-pharmacological interventions that are usually tried in a least to most invasive order. The first line of intervention is often to administer a uterotonic drug, preferably oxytocin. This poses a challenge to LMICs because oxytocin requires a cold-chain storage, which many LMICs countries lack. Therefore, uterotonics and non-pharmacologic interventions have increasingly been used in these regions. The final and ultimate life saving measure to stop bleeding is a hysterectomy, which is often not available in these rural places where home births take place, and has led to higher mortality rates. Prevention measures of PPH include increasing antenatal care (ANC) use and practicing active management of the third stage of labor (AMTSL) with all pregnancies. Use of ANC and ultrasound technology can help identify the biological risk factors that make a woman more likely to experience PPH. Solutions to lowering the occurrence of PPH in LMICs involve increasing resources and access to healthcare. An important part to increasing access is increasing the number of skilled health facilities and health providers. Community health workers (CHW) and skilled birth attendants (SBA) are vital to increasing the amount and acceptability of care in these regions. These workers are trusted members of the community that can help educate and bring resources to women, as well as women to the resources. Solutions to stopping PPH need to consider the affordability, acceptability and accessibility in order to reach people in remote areas with limited resources. Both immediate short-term interventions and long-term, longitudinal healthcare reform are necessary to save mothers in LMICs.

Massive bilateral adrenal hemorrhage occurring in the postoperative period is an unusual but potentially life-threatening complication of any abdominal operation. The diagnosis is often difficult due to the nonspecific nature of the clinical presentation, which is easily attributable to other more common postoperative conditions. We report a case of bilateral adrenal hemorrhage resulting in acute primary adrenal insufficiency following an otherwise-uncomplicated laparoscopic cholecystectomy, which has not previously been described. An awareness of the possibility of this uncommon condition complicating laparoscopic cholecystectomy may lead to a higher index of suspicion, which is important in timely diagnosis and prompt treatment.

Subarachnoid hemorrhage (SAH) causes 5% of all strokes and is responsible for about 18,000 deaths per year in the United States (Aneurysmal Subarachnoid Hemorrhage, 2008). The incidence of SAH has been estimated at 6 to 8 per 100,000 persons per year (Linn, Rinkel, Algra, & van Gijn, 1996). In nearly 15% (range 5–34%) of patients with SAH, no source of hemorrhage can be identified via four-vessel cerebral angiography (Alen et al., 2003; Gupta et al., 2009), resulting in two major types of SAH: aneurysmal (ASAH) and nonaneurysmal (NASAH). Anecdotal evidence and contradictory research suggest that patients with NASAH experience some of the same health-related quality of life (HRQOL) issues as patients with ASAH. The purpose of this quantitative survey design study was to compare health-related quality of life (HRQOL) 1 to 3 years post-hemorrhage in patients who have experienced a NASAH to those who have experienced an ASAH. This is the first US study to specifically investigate HRQOL in NASAH and the second study comparing HRQOL outcomes between aneurysmal and nonaneurysmal subarachnoid hemorrhage patients. Our results are comparable to the first study by Hutter and Gilsbach, (1995), which also found that the two groups are much more similar than different. There were no significant differences between 28 of the 36 demographic and clinical characteristics examined in this study. Our study confirms previous findings that there is a significant impact on employment for both hemorrhage groups and an even greater inability to return to work for the NASAH patients. The nonaneurysmal group had more physical symptom complaints while the aneurysmal group had more emotional symptoms. Lastly, both groups had low levels of PTSD, and these levels did not differ significantly between groups. However, PTSD and social support were shown by regression analysis to impact HRQOL for both groups. We recommend that clinicians assess for PTSD in all subarachnoid hemorrhage patients and institute treatment early, which will decrease the negative effects on HRQOL. This may include offering psychological services or social work early in the hospital course to all SAH patients. Further research and policy changes are needed to assist in interventions that improve vocational reintegration after SAH. NASAH patients should no longer be referred to as having suffered a “benign hemorrhage.” They have had a life changing hemorrhage that may forever change their lives and impact their HRQOL.

Advances in medical technology have provided the mechanisms for sustaining life in premature and low-birthweight infants, resulting in the survival of more of these infants. Low-birthweight (LBW) and preterm infants are placed at risk by a number of medical complications, including intraventricular hemorrhage (IVH). The outcome of low-birthweight infants with intraventricular hemorrhage has been the subject of a great deal of research and continues to be a much-discussed topic in the medical and psychological communities. As more data become available, it appears that more questions arise concerning the later neuodevelopmental and neuropsychological outcome of these infants. For this reason, research concerning the later status of infants born with intraventricular hemorrhage is needed. The purpose of this study was to determine if there are differences in cognitive and motor functioning among infants with intraventricular hemorrhage (IVH), infants who were low birthweight (LBW), and normal-birthweight (NBW) infants. Forty-four subjects (10 with mild IVH, 9 with severe IVH, 12 LBW, and 13 NBW), who were born between January 1, 1984, and June 1, 1985, and were either patients in the neonatal intensive care unit at University of Utah Medical Center (the IVH and LBW infants) or were residents of the well-baby nursery (the NBW infants) at University of Utah Medical Center, served as the sample population. The subjects were tested at 3 to 4.5 years of age using the Stanford-Binet Intelligence Scales (Fourth Edition) and the motor section of the McCarthy Scales of Children's Abilities. In addition, infant medical data were obtained from medical records, and demographic data were collected including mother's age at time of birth, family income, mother's and father's education level, and birth order of the infant. The MIVH, SIVH, and LBW groups had significantly lower gestational ages and birthweights and significantly more medical complications than did the NBW group. The MIVH and SIVH groups also had significantly lower birthweight and gestational ages than did the LBW group, but approximately equivalent numbers of medical complications. Significant group differences were found only between the MIVH and NBW groups on the McCarthy motor score, with the MIVH group appearing to outperform the NBW group following statistical manipulation with analysis of covariance. No other significant group differences were found. Further research with a larger sample is recommended in order to more fully understand the later outcome following LBW and IVH.

Introduction Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is an invasivetechnique aimed at stabilizing hemodynamically unstable patients. The technique is underconstant development and in 2016 a new REBOA balloon requiring a smaller sized sheathwas introduced aiming to decrease complications and mortality. Studies show contradictoryfindings concerning outcome and complications of REBOA. Aim To investigate if survival and complications of patients treated with REBOA changed overtime by comparing two time periods, 2011-2015 and 2016-2020. Methods This was a retrospective registry study. Data was extracted from the Aortic Balloon Occlusion(ABO) trauma registry and 217 patients were included in the study. Patients were divided intotwo calendar periods, an early period (2011-2015) and a late period (2016-2020). Results Mortality at the emergency department was 24 % in the early period compared to 9 % in thelate period (p= 0.018). Mortality within 24 hours was reported in 40 % in the early period and36 % in the late period. In the early period, mortality within 30 days was 59 % and 36 % inthe late period. Access related complications such as extremity ischemia was reported in 1 %in the early period and 12 % in the late period (p = 0.001). Conclusion Early mortality at the emergency department has decreased over time. Access relatedcomplications were present in both the early and late period but extremity ischemia was morecommon in the late period.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24785号 / 医博第4977号 / 新制||医||1066(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 金子 新, 教授 YOUSSEFIAN Shohab, 教授 阪上 優 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Primary angiitis of the central nervous system (PACNS) is a rare form of vasculitis. It is a diagnosis of exclusion and often diagnosed post mortem on pathologic evaluation. Cerebral angiography can be suggestive, but biopsy is required. Symptoms can vary from headache to focal cranial nerve deficits. On the more severe spectrum, patients can present with ischemic and vary rarely hemorrhagic stroke. We present in this case report key clinical pearls regarding suspected diagnosis. Younger patients with cortical hemorrhages may have PACNS instead of the more common cerebral amyloid angiopathy. Early suspicion may aid in initiating effective treatment as we highlight in the discussion.