Necrotizing pancreatitis with invasive candidiasis and candidemia due to Candida albicans and pan-echinocandin-resistant Candidaglabrata.

We report on a 64-year-old man with necrotizing pancreatitis related, invasive candidiasis, and candidemia. Despite a multidisciplinary management including antifungal therapy, endoscopic interventions and surgery, the patients' infection progressed and lead to colon perforation, retroperitoneal abscess formation, and polymicrobial bloodstream infections. Resistance to echinocandins in Candida glabrata further complicated the course. This report emphasizes the need for vigilant monitoring and exploring alternative therapeutic approaches for patients in critical conditions.

Learning curve of achieving competency in emergency endoscopy in upper gastrointestinal bleeding: how much experience is necessary?

OBJECTIVES: The management of upper gastrointestinal bleeding (UGIB) has seen rapid advancements with revolutionising innovations. However, insufficient data exist on the necessary number of emergency endoscopies needed to achieve competency in haemostatic interventions. DESIGN: We retrospectively analysed all oesophagogastroduodenoscopies with signs of recent haemorrhage performed between 2015 and 2022 at our university hospital. A learning curve was created by plotting the number of previously performed oesophagogastroduodenoscopies with signs of recent haemorrhage against the treatment failure rate, defined as failed haemostasis, rebleeding and necessary surgical or radiological intervention. RESULTS: The study population included 787 cases with a median age of 66 years. Active bleeding was detected in 576 cases (73.2%). Treatment failure occurred in 225 (28.6%) cases. The learning curve showed a marked decline in treatment failure rates after nine oesophagogastroduodenoscopies had been performed by the respective endoscopists followed by a first plateau between 20 and 50 procedures. A second decline was observed after 51 emergency procedures followed by a second plateau. Endoscopists with experience of <10 emergency procedures had higher treatment failure rates compared with endoscopists with >51 emergency oesophagogastroduodenoscopies performed (p=0.039) or consultants (p=0.041). CONCLUSIONS: Our data suggest that a minimum number of 20 oesophagogastroduodenoscopies with signs of recent haemorrhage is necessary before endoscopists should be considered proficient to perform emergency procedures independently. Endoscopists might be considered as advanced-qualified experts in managing UGIB after a minimum of 50 haemostatic procedure performed. Implementing recommendations on minimum numbers of emergency endoscopies in education programmes of endoscopy trainees could improve their confidence and competency in managing acute UGIB.

Timing of endoscopy in patients with elevated lactate levels and acute upper gastrointestinal bleeding; a retrospective comparative study.

BACKGROUND/AIMS: While current guidelines recommend performing endoscopy within 24 h in case of acute upper gastrointestinal bleeding (AUGIB), the precise timing remains an issue of debate. Lactate is an established parameter for risk stratification in a variety of medical emergencies. This study evaluated the predictive ability of elevated lactate levels in identifying patients with UGIB, who may benefit from emergent endoscopy. METHODS: We retrospectively analyzed all patients with elevated lactate levels, who presented to our emergency department between 01 January 2015 and 31 December 2019 due to suspected AUGIB. RESULTS: Of 134 included cases, 81.3% had an Charlson comorbidity index of ≥3 and 50.4% presented with shock. Fifteen (11.2%) patients died and mortality rates rose with increasing lactate levels. Emergent endoscopy within 6 h (EE) and non-EE were performed in 64 (47.8%) and 70 (52.2%) patients, respectively. Patients who underwent EE had lower systolic blood pressure (107.6 mmHg vs. 123.2 mmHg; p = 0.001) and received blood transfusions more frequently (79.7% vs 64.3%; p = 0.048), but interestingly need for endoscopic intervention (26.6% vs 20.0%; p = 0.37), rebleeding (17.2% vs. 15.7%; p = 0.82) and mortality (9.4% vs. 11.4%; p = 0.7) did not differ significantly. CONCLUSION: In conclusion, our findings support the recommendations of current guidelines to perform non-EE after sufficient resuscitation and management of comorbid illnesses.

Prognostic assessment of liver cirrhosis and its complications: current concepts and future perspectives.

Liver cirrhosis is an irreversible stage of chronic liver disease with varying clinical course. Acute decompensation of liver cirrhosis represents a watershed in prognosis and is characterized by the occurrence of clinical complications such as ascites, jaundice, hepatic encephalopathy, infections, or portal-hypertensive hemorrhages. Emergent data indicate that an acute decompensation can be subdivided into stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on chronic liver failure (pre-ACLF) and acute-on chronic liver failure (ACLF), while the mortality risk varies greatly between the respective subgroups. ACLF is the most severe form of acutely decompensated cirrhosis and characterized by the development of organ failure(s) and a high short-term mortality. Due to the dynamic disease course of acute decompensation, it is paramount to detect patients at particular risk for severe complications those at high risk for developing ACLF as early as possible in order to initiate optimal management. This review describes new concepts and perspectives in the definition and classification of decompensated cirrhosis and provides on overview on emerging predictive scoring systems, non-invasive measurement methods and new biomarkers, which allow an early identification of patients with acute decompensation at risk.

[Alcoholic hepatitis - current and future treatment approaches]. / Alkoholische Hepatitis ­ Aktuelle und zukünftige Behandlungskonzepte.

Acute severe alcoholic hepatitis is a serious disease with poor prognosis. As a result of an improved understanding of the underlying pathomechanisms, a variety of new, innovative therapeutic modalities are currently being investigated that may help to improve prognosis. New approaches include the application of anti-inflammatory agents (e.g., interleukin-1 inhibitors), modifications of the gut-liver axis via fecal microbiome transfer or the administration of non-absorbable antibiotics (e.g., rifaximin), and drugs to enhance hepatocellular regeneration (e.g., interleukin-22 agonists). This article describes current management concepts of alcoholic hepatitis and provides an overview of new potential treatment approaches.

Management of alcoholic hepatitis: A clinical perspective.

Alcohol-associated liver disease is the primary cause of liver-related mortality worldwide and one of the most common indications for liver transplantation. Alcoholic hepatitis represents the most acute and severe manifestation of alcohol-associated liver disease and is characterized by a rapid onset of jaundice with progressive inflammatory liver injury, worsening of portal hypertension, and an increased risk for multiorgan failure in patients with excessive alcohol consumption. Severe alcoholic hepatitis is associated with a poor prognosis and high short-term mortality. During the COVID-19 pandemic, rates of alcohol-associated hepatitis have increased significantly, underscoring that it is a serious and growing health problem. However, adequate management of alcohol-associated hepatitis and its complications in everyday clinical practice remains a major challenge. Currently, pharmacotherapy is limited to corticosteroids, although these have only a moderate effect on reducing short-term mortality. In recent years, translational studies deciphering key mechanisms of disease development and progression have led to important advances in the understanding of the pathogenesis of alcoholic hepatitis. Emerging pathophysiology-based therapeutic approaches include anti-inflammatory agents, modifications of the gut-liver axis and intestinal dysbiosis, epigenetic modulation, antioxidants, and drugs targeting liver regeneration. Concurrently, evidence is increasing that early liver transplantation is a safe treatment option with important survival benefits in selected patients with severe alcoholic hepatitis not responding to medical treatment. This narrative review describes current pathophysiology and management concepts of alcoholic hepatitis, provides an update on emerging treatment options, and focuses on the need for holistic and patient-centred treatment approaches to improve prognosis.

A convolutional neural network for bleeding detection in capsule endoscopy using real clinical data.

BACKGROUND: The goal of the present study was to develop a convolutional neural network for the detection of bleedings in capsule endoscopy videos using realistic clinical data from one single-centre. METHODS: Capsule endoscopy videos from all 133 patients (79 male, 54 female; meanage = 53.73 years, SDage = 26.13) who underwent capsule endoscopy at our institution between January 2014 and August 2018 were screened for pathology. All videos were screened for pathology by two independent capsule experts and confirmed findings were checked again by a third capsule expert. From these videos, 125 pathological findings (individual episodes of bleeding spanning a total of 5696 images) and 103 non-pathological findings (sections of normal mucosal tissue without pathologies spanning a total of 7420 images) were used to develop and validate a neural network (Inception V3) using transfer learning. RESULTS: The overall accuracy of the model for the detection of bleedings was 90.6% [95%CI: 89.4%-91.7%], with a sensitivity of 89.4% [95%CI: 87.6%-91.2%] and a specificity of 91.7% [95%CI: 90.1%-93.2%]. CONCLUSION: Our results show that neural networks can detect bleedings in capsule endoscopy videos under realistic, clinical conditions with an accuracy of 90.6%, potentially reducing reading time per capsule and helping to improve diagnostic accuracy.

Blood pressure changes during tenofovir-based antiretroviral therapy among people living with HIV in Lilongwe, Malawi: results from the prospective LighTen Cohort Study.

BACKGROUND: Sub-Saharan Africa is one of the regions in the world with the highest numbers of uncontrolled hypertension as well as people living with HIV/AIDS (PLHIV). However, the association between hypertension and antiretroviral therapy is controversial. METHODS: Participant demographics, medical history, laboratory values, WHO clinical stage, current medication, and anthropometric data were recorded at study entry and during study visits at 1, 3, 6 months, and every 6 months thereafter until month 36. Patients who stopped or changed their antiretroviral therapy (tenofovir, lamivudine, efavirenz) were censored on that day. Office blood pressure (BP) was categorized using ≥ 2 measurements on ≥ 2 occasions during the first three visits. Factors associated with systolic and mean BP were analyzed using bivariable and multivariable multilevel linear regression. RESULTS: 1,288 PLHIV (751 females, 58.3%) could be included and 832 completed the 36 months of observation. Weight gain and a higher BP level at study entry were associated with an increase in BP (p < 0.001), while female sex (p < 0.001), lower body weight at study entry (p < 0.001), and high glomerular filtration rate (p = 0.009) protected against a rise in BP. The rate of uncontrolled BP remained high (73.9% vs. 72.1%) and despite indication treatment, adjustments were realized in a minority of cases (13%). CONCLUSION: Adherence to antihypertensive treatment and weight control should be addressed in patient education programs at centers caring for PLHIV in low-resources settings like Malawi. Together with intensified training of medical staff to overcome provider inertia, improved control rates of hypertension might eventually be achieved. TRIAL REGISTRATION: NCT02381275.

Comparison of Lactate Clearance with Established Risk Assessment Tools in Predicting Outcomes in Acute Upper Gastrointestinal Bleeding.

Early risk stratification is mandatory in acute upper gastrointestinal bleeding (AUGIB) to guide optimal treatment. Numerous risk scores were introduced, but lack of practicability led to limited use in daily clinical practice. Lactate clearance is an established risk assessment tool in a variety of diseases, such as trauma and sepsis. Therefore, this study compares the predictive ability of pre-endoscopic lactate clearance and established risk scores in patients with AUGIB at the University Hospital of Cologne. Active bleeding was detected in 27 (25.2%) patients, and hemostatic intervention was performed in 35 (32.7%). In total, 16 patients (15%) experienced rebleeding and 12 (11.2%) died. Initially, lactate levels were elevated in 64 cases (59.8%), and the median lactate clearance was 18.7% (2.7-48.2%). Regarding the need for endoscopic intervention, the predictive ability of Glasgow Blatchford Score, pre-endoscopic Rockall score, initial lactate and lactate clearance did not differ significantly, and their area under the receiver operating characteristic curves were 0.658 (0.560-0.747), 0.572 (0.473-0.667), 0.572 (0.473-0.667) and 0.583 (0.483-0.677), respectively. Similar results were observed in relation to rebleeding and mortality. In conclusion, lactate clearance had comparable predictive ability compared to established risk scores. Further prospective research is necessary to clarify the potential role of lactate clearance as a reliable risk assessment tool in AUGIB.

[Gastrointestinal and hepatic emergencies in acute and emergency care]. / Gastrointestinale und hepatologische Notfälle in der klinischen Akut- und Notfallmedizin.

Acute gastrointestinal emergencies are one of the most common presentations to the emergency department. If the main symptom is acute abdominal pain, this is referred to as "acute abdomen". An acute abdomen demands urgent attention and treatment and can be caused by different pathologies (e.g., peptic ulcer disease, acute pancreatitis, diverticulitis). Hepatic emergencies include acute liver failure and acute-on-chronic liver failure. Due to the large number of possible differential diagnoses with variable clinical symptoms, rapid diagnosis of the underlying etiology of gastrointestinal and liver emergencies is a major challenge in daily clinical practice. A structured approach and prompt initiation of adequate diagnostic and treatment measures are essential in order to reduce mortality.

Perinatal Obesity Sensitizes for Premature Kidney Aging Signaling.

Chronic Kidney Disease (CKD), a global health burden, is strongly associated with age-related renal function decline, hypertension, and diabetes, which are all frequent consequences of obesity. Despite extensive studies, the mechanisms determining susceptibility to CKD remain insufficiently understood. Clinical evidence together with prior studies from our group showed that perinatal metabolic disorders after intrauterine growth restriction or maternal obesity adversely affect kidney structure and function throughout life. Since obesity and aging processes converge in similar pathways we tested if perinatal obesity caused by high-fat diet (HFD)-fed dams sensitizes aging-associated mechanisms in kidneys of newborn mice. The results showed a marked increase of γH2AX-positive cells with elevated 8-Oxo-dG (RNA/DNA damage), both indicative of DNA damage response and oxidative stress. Using unbiased comprehensive transcriptomics we identified compartment-specific differentially-regulated signaling pathways in kidneys after perinatal obesity. Comparison of these data to transcriptomic data of naturally aged kidneys and prematurely aged kidneys of genetic modified mice with a hypomorphic allele of Ercc1, revealed similar signatures, e.g., inflammatory signaling. In a biochemical approach we validated pathways of inflammaging in the kidneys after perinatal obesity. Collectively, our initial findings demonstrate premature aging-associated processes as a consequence of perinatal obesity that could determine the susceptibility for CKD early in life.

Heterogeneous effects of individual high-fat diet compositions on phenotype, metabolic outcome, and hepatic proteome signature in BL/6 male mice.

The multitude of obesogenic diets used in rodent studies can hardly be overviewed. Since standardization is missing and assuming that individual compositions provoke individual effects, the choice of quality, quantity and combination of diet ingredients seems to be crucial for the outcome and interpretation of obesity studies. Therefore, the present study was conducted to compare the individual effects of three commonly used obesogenic diets, mainly differing in sugar and fat content. Besides basic phenotypic and metabolic characterization, one main aspect was a comparative liver proteome analysis. As expected, the obtained results picture differentiated consequences mainly depending on fat source and/or fat- and sugar quantity. By confirming the general presumption that the choice of nutritional composition is a pivotal factor, the present findings demonstrate that a conscious selection is indispensable for obtaining reliable and sound results in obesity research. In conclusion, we strongly recommend a careful selection of the appropriate diet in advance of a new experiment, taking into account the specific research question.