Diagnostic and Prognostic Value of Serum Leptin in Critically Ill Patients with Acute versus Acute-on-Chronic Liver Failure.

Differentiation between acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) can be challenging in patients with de novo liver disease but is important to indicate the referral to a transplant center and urgency of organ allocation. Leptin, an adipocyte-derived cytokine that regulates energy storage and satiety, has multiple regulatory functions in the liver. We enrolled 160 critically ill patients with liver disease and 20 healthy individuals to measure serum leptin concentrations as a potential biomarker for diagnostic and prognostic purposes. Notably, patients with ALF had higher concentrations of serum leptin compared to patients with decompensated advanced chronic liver disease (dACLD) or ACLF (110 vs. 50 vs. 29 pg/mL, p < 0.001). Levels of serum leptin below 56 pg/mL excluded ALF in patients with acute hepatic disease, with a negative predictive value (NPV) of 98.8% in our cohort. Lastly, serum leptin did not show any dynamic changes within the first 48 h of ICU treatment, especially not in comparison with patients with ALF vs. ACLF or survivors vs. non-survivors. In conclusion, serum leptin may represent a helpful biomarker to exclude ALF in critically ill patients who present with acute liver dysfunction.

Ventricular tachycardia due to left ventricular metastasis: A case report.

We present the case of a 60-year-old male patient who was admitted to our hospital after experiencing a syncopal episode. First ECGs showed sinus rhythm with polymorphic premature ventricular complexes and later ventricular tachycardia with a left bundle branch block morphology were recorded. Imaging with TEE and MRI revealed a space-occupying lesion in the left ventricle, which was ultimately identified as a rare cardiac metastasis of renal cell carcinoma. Treatment was initiated with monoclonal antibodies resulting in lesion regression. This case highlights the importance of comprehensive diagnostic in patients with history of malignancy.

Elevated Serum KIM-1 in Sepsis Correlates with Kidney Dysfunction and the Severity of Multi-Organ Critical Illness.

The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1 portends complex immunoregulation and is elevated after exposure to lipopolysaccharides. It thus may represent a biomarker in critical illness, sepsis, and sepsis-associated AKI (SA-AKI). To characterise and compare KIM-1 in these settings, we analysed KIM-1 serum concentrations in 192 critically ill patients admitted to the intensive care unit. Irrespective of kidney dysfunction, KIM-1 serum levels were significantly higher in patients with sepsis compared with other critical illnesses (191.6 vs. 132.2 pg/mL, p = 0.019) and were highest in patients with urogenital sepsis, followed by liver failure. Furthermore, KIM-1 levels were significantly elevated in critically ill patients who developed AKI within 48 h (273.3 vs. 125.8 pg/mL, p = 0.026) or later received renal replacement therapy (RRT) (299.7 vs. 146.3 pg/mL, p < 0.001). KIM-1 correlated with markers of renal function, inflammatory parameters, hematopoietic function, and cholangiocellular injury. Among subcomponents of the SOFA score, KIM-1 was elevated in patients with hyperbilirubinaemia (>2 mg/dL, p < 0.001) and thrombocytopenia (<150/nL, p = 0.018). In univariate and multivariate regression analyses, KIM-1 predicted sepsis, the need for RRT, and multi-organ dysfunction (MOD, SOFA > 12 and APACHE II ≥ 20) on the day of admission, adjusting for relevant comorbidities, bilirubin, and platelet count. Additionally, KIM-1 in multivariate regression was able to predict sepsis in patients without prior (CKD) or present (AKI) kidney injury. Our study suggests that next to its established role as a biomarker in kidney dysfunction, KIM-1 is associated with sepsis, biliary injury, and critical illness severity. It thus may offer aid for risk stratification in these patients.

Atraumatic splenic rupture - unexpected consequences of a world trip.

Diagnostic routine and knowledge about the therapy regimes of infectious diseases like malaria gain in importance due to globalization, global warming, and increasing numbers of refugees. We report a case of a 66-year-old patient who presented with severe abdominal pain, most prominent in the left upper abdomen. He was recently hospitalized with severe falciparum malaria, diagnosed after returning from a trip around the world. Upon readmission, laboratory results showed post-artesunate delayed hemolysis. The ultrasound examination was highly suspicious of splenic rupture, confirmed by the immediately performed CT scan. In this case, the prompt diagnosis allowed the initiation of adequate conservative therapy including intensive care monitoring and hemodynamic stabilization.

Soluble Neuropilin-1 Is Elevated in Sepsis and Correlates with Organ Dysfunction and Long-Term Mortality in Critical Illness.

Critical illness and sepsis may cause organ failure and are recognized as mortality drivers in hospitalized patients. Neuropilin-1 (NRP-1) is a multifaceted transmembrane protein involved in the primary immune response and is expressed in immune cells such as T and dendritic cells. The soluble form of NRP-1 (sNRP-1) acts as an antagonist to NRP-1 by scavenging its ligands. The aim of this study was to determine the value of sNRP-1 as a biomarker in critical illness and sepsis. We enrolled 180 critically ill patients admitted to a medical intensive care unit and measured serum sNRP-1 concentrations at admission, comparing them to 48 healthy individuals. Critically ill and septic patients showed higher levels of sNRP-1 compared to healthy controls (median of 2.47 vs. 1.70 nmol/L, p < 0.001). Moreover, sNRP-1 was also elevated in patients with sepsis compared to other critical illness (2.60 vs. 2.13 nmol/L, p = 0.01), irrespective of disease severity or organ failure. In critically ill patients, sNRP-1 is positively correlated with markers of kidney and hepatic dysfunction. Most notably, critically ill patients not surviving in the long term (one year after admission) showed higher concentrations of sNRP-1 at the time of ICU admission (p = 0.036), with this association being dependent on the presence of organ failure. Critically ill and septic patients exhibit higher serum concentrations of circulating sNRP-1, which correlates to organ failure, particularly hepatic and kidney dysfunction.

Underfunding of German university-based high-performance medicine exemplified by the treatment of varices in cirrhosis.

Facing increasing economization in the health care sector, clinicians have to adapt not only to the ever-growing economic challenges, but also to a patient-oriented health care. Treatment costs are the most important variable for optimizing success when facing scarce human resources, increasing material- and infrastructure costs in general, as well as low revenue flexibility due to flat rates per case in Germany, the so-called Diagnosis-Related Groups (DRG). University hospitals treat many patients with particularly serious illnesses. Therefore, their share of complex and expensive treatments, such as liver cirrhosis, is significantly higher. The resulting costs are not adequately reflected in the DRG flat rate per case, which is based on an average calculation across all hospitals, which increases this economic pressure. Thus, the aim of this manuscript is to review cost and revenue structures of the management of varices in patients with cirrhosis at a university center with a focus on hepatology. For this monocentric study, the data of 851 patients, treated at the Gastroenterology Department of a University Hospital between 2016 and 2020, were evaluated retrospectively and anonymously. Medical services (e.g., endoscopy, radiology, laboratory diagnostics) were analyzed within the framework of activity-based-costing. As part of the cost unit accounting, the individual steps of the treatment pathways of the 851 patients were monetarily evaluated with corresponding applicable service catalogs and compared with the revenue shares of the cost center and cost element matrix of the German (G-) DRG system. This study examines whether university-based high-performance medicine is efficient and cost-covering within the framework of the G-DRG system. We demonstrate a dramatic underfunding of the management of varicose veins in cirrhosis in our university center. It is therefore generally questionable whether and to what extent an adequate care for this patient collective is reflected in the G-DRG system.

[Clinical acute and emergency medicine curriculum-focus on internal medicine : Recommendations for advanced training in internal medicine in the emergency department]. / Curriculum Klinische Akut- und Notfallmedizin ­ Schwerpunkt Innere Medizin : Empfehlung zu Weiterbildungsinhalten der Inneren Medizin in der Notaufnahme.

In Germany, physicians qualify for emergency medicine by combining a specialty medical training-e.g. internal medicine-with advanced training in emergency medicine according to the statutes of the State Chambers of Physicians largely based upon the Guideline Regulations on Specialty Training of the German Medical Association. Internal medicine and their associated subspecialities represent an important column of emergency medicine. For the internal medicine aspects of emergency medicine, this curriculum presents an overview of knowledge, skills (competence levels I-III) as well as behaviours and attitudes allowing for the best treatment of patients. These include general aspects (structure and process quality, primary diagnostics and therapy as well as indication for subsequent treatment; resuscitation room management; diagnostics and monitoring; general therapeutic measures; hygiene measures; and pharmacotherapy) and also specific aspects concerning angiology, endocrinology, diabetology and metabolism, gastroenterology, geriatric medicine, hematology and oncology, infectiology, cardiology, nephrology, palliative care, pneumology, rheumatology and toxicology. Publications focussing on contents of advanced training are quoted in order to support this concept. The curriculum has primarily been written for internists for their advanced emergency training, but it may generally show practising emergency physicians the broad spectrum of internal medicine diseases or comorbidities presented by patients attending the emergency department.

Spillover effects of reminder nudges in complex environments.

We present an experiment on the immediate and lasting effects of reminder nudges in a complex environment. In the study, 1,542 subjects face a setting where, within a brief time frame, they have to pay attention to and perform multiple actions in a computer game. The experiment investigates i) the effect of reminders on the reminded actions and their spillovers on nonreminded actions; ii) spillovers between multiple nudges when the number of reminded actions is increased; and iii) intertemporal spillovers from having been exposed to reminders on actions after reminders are withdrawn. Our findings reveal, first, that reminders have a positive effect on the overall number of actions performed. It results from the positive direct effect on the reminded actions dominating the negative spillovers on nonreminded actions. These negative effects are notable in our setting, where reminders could potentially have positive spillovers by freezing attention or by indirectly prompting actions similar to the reminded ones. Second, we observe that reminder nudges are scalable. Increasing the number of reminded actions leads subjects to take more actions overall, albeit with diminishing returns and more pronounced negative spillover effects. Third, after reminders are withdrawn, the positive effect on reminded actions diminishes, while negative spillovers on nonreminded actions persist, thus rendering reminders ineffective in increasing the overall number of actions performed.

Students and physicians differ in perception of quality of life in patients with tumors of the upper gastrointestinal tract.

Health-related quality of life (HRQoL) has recently gained importance as treatment options for tumors of the upper GI tract lead to improved long-term survival. HRQoL is often estimated by physicians even though their reliability and the impact of outside factors such as contact time and level of medical education is unclear. Therefore, in this study we investigated the correlation between physicians', students', and patients' assessment of HRQoL. 54 patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaires EORTC QLQ-C30 and QLQ-OG25. Attending physicians and medical students filled out the same questionnaires through estimation of patients' HRQoL. Correlation was assessed through Pearson's and Kendall's τb coefficients. Physicians' and patients' assessments correlated for one out of six of the functional and a third of the symptom scores. Students' and patients' assessments correlated for one third of the functional and two thirds of the symptom scores. Students tended to underestimate patients' symptom burden while physicians tended to overestimate it. Physicians failed to correctly assess several pathognomonic symptoms in this study. Students showed higher correlation with patients' symptoms than physicians. Even so, this adds to mounting evidence that shows the benefit of using patient-reported outcomes as a gold standard regarding HRQoL.

Comorbidities, mortality and metabolic profile in individuals with primary biliary cholangitis-A Phenome-Wide-Association-Study.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is a chronic, immune-mediated liver disease that can lead to fibrosis and cirrhosis. In this cohort study, we aimed to investigate morbidity and mortality in conjunction with metabolomic changes of PBC in a UK population-based cohort. METHODS: 454 participants with PBC and 908 propensity score (age, sex, BMI, ethnicity) matched controls without liver disease were included in the study. A subset of participants with PBC and controls were analysed for their metabolomic profile. Further, PBC-associated comorbidities were investigated by PheWAS analysis. Lastly, we assessed causes of death in individuals with PBC using a Fine and Grey competing-risks regression model. RESULTS: Compared to the control group, various pathways associated with the metabolism of amino acids, lipids, and liver biochemistry were significantly enriched in individuals with PBC. We found reduced levels of S-HDL-cholesterol and Glycoprotein Acetyls in individuals with PBC as well as an association with diseases of the circulatory system. Notably, PBC individuals had a higher prevalence of digestive diseases, autoimmune diseases, cardiovascular diseases, anaemias, mental disorders, and urinary tract infections compared to the control group. Strikingly, the overall mortality was almost three times higher in the PBC group compared to the control group, with diseases of the digestive system accounting for a significant elevation of the death rate. A subsequent analysis, enhanced by propensity score matching that included the APRI score, demonstrated that the observed morbidity could not be exclusively attributed to advanced hepatic disease. CONCLUSIONS: Our study provides a detailed perspective on the morbidity of individuals with PBC. The exploration of potential effects of disease state on morbidity suggest that early detection and early treatment of PBC could enhance patient prognosis and prevent the onset of comorbid diseases. Finally, the metabolomic alterations could represent a link between the pathophysiological processes underlying PBC development, progression, and associated morbidity.

Quality of Life, Sarcopenia and Nutritional Status in Patients with Esophagogastric Tumors before and after Neoadjuvant Therapy.

(1) Background: Health-related quality of life (HRQoL) gains importance as novel treatment options for individuals with esophagogastric tumors to improve long-term survival. Impaired HRQoL has been shown to be a predictor of overall survival. Sarcopenia is a known prognostic factor for postoperative complications. As the regular control of sarcopenia through CT scans might not always be possible and HRQoL and nutritional scores are easier to obtain, this study aimed to assess the relationship between nutritional scores, HRQoL and skeletal muscle mass in patients undergoing chemotherapy for cancers of the upper gastrointestinal tract. (2) Methods: Eighty patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaire, EORTC's QLQ-C30. Nutritional status was assessed using the MNA, MUST and NRS 2002 scores. Sarcopenia was determined semi-automatically based on the skeletal muscle index at the L3 vertebrae level in staging CT scans. (3) Results: In chemo-naïve patients, HRQoL summary scores correlated significantly with nutritional scores and SMI. SMI and HRQoL prior to neoadjuvant therapy correlated significantly with SMI after treatment. (4) Conclusions: HRQoL is a helpful tool for assessing patients' overall constitution. The correlation of HRQoL summary scores and SMI might allow for a rough assessment of skeletal muscle status through HRQoL assessment in chemo-naïve patients.

Soluble Semaphorin 4D Serum Concentrations Are Elevated in Critically Ill Patients with Liver Cirrhosis and Correlate with Aminotransferases.

Semaphorin 4D (Sema4D), also known as CD100, is a multifunctional transmembrane protein with immunoregulatory functions. Upon the activation of immune cells, soluble Semaphorin 4D (sSema4D) is proteolytically cleaved from the membrane by metalloproteinases. sSema4D levels are elevated in various (auto-)inflammatory diseases. Our aim was to investigate sSema4D levels in association with sepsis and critical illnesses and to evaluate sSema4D's potential as a prognostic biomarker. We measured sSema4D levels in 192 patients upon admission to our medical intensive care unit. We found similar levels of sSema4D in 125 patients with sepsis compared to 67 non-septic patients. sSema4D levels correlated with leukocytes but not with other markers of systemic inflammation such as C-reactive protein or procalcitonin. Most interestingly, in a subgroup of patients suffering from pre-existing liver cirrhosis, we observed significantly higher levels of sSema4D. Consistently, sSema4D was also positively correlated with markers of hepatic and cholestatic injury. Our study suggests that sSema4D is not regulated in sepsis compared to other causes of critical illness. However, sSema4D seems to be associated with hepatic injury and inflammation.

Impairment of Nutritional Status and Quality of Life Following Minimal-Invasive Esophagectomy-A Prospective Cohort Analysis.

Minimal-invasive resection of the esophagus for esophageal cancer has led to a relevant decrease in postoperative morbidity. Postoperatively, patients still suffer from surgical and adjuvant therapy-related symptoms impairing nutrition and quality of life. The aim of this study was to evaluate the nutritional status and associated symptoms six months after esophagectomy. Patients who attended follow-up examination six months after minimal-invasive esophagectomy were included. Blood and fecal tests, quality of life surveys (QLQ-C30 and QLQ-OG25) and nutritional risk screening (NRS) were performed. Twenty-four patients participated. The mean weight loss was 11 kg. A significant decrease in vitamin B12 (737 to 467 pg/mL; p = 0.033), ferritin (302 to 126 ng/mL; p = 0.012) and haptoglobin (227 to 152 mg/dL; p = 0.025) was found. In total, 47% of the patients had an impaired pancreatic function (fecal elastase < 500 µg/g). Physical (72 to 58; p = 0.034) and social functioning (67 to 40; p = 0.022) was significantly diminished, while self-reported global health status remained stable (52 to 54). The number of patients screened and found to be in need of nutritional support according to NRS score decreased slightly (59% to 52%). After MIE, patients should be meticulously monitored for nutritional status after surgery.

[From the forest to the ICU and back: an investigative work-up of Amanita phalloides poisoning]. / Vom Wald auf die Intensivstation und zurück: Eine detektivische Aufarbeitung einer Knollenblätterpilzvergiftung.

With over 90% of deaths following mushroom ingestion, poisoning with Amatoxin is one of the most dangerous food intoxications. Despite numerous case reports, treatment recommendations are based on a moderate level of evidence due to a lack of randomized controlled trials.We present the case of a 32-year-old patient who presented with acute liver failure after Amanita phalloides (green death cap mushroom) ingestion and whose therapeutic success was significantly influenced by the administration of activated charcoal, silibinin, and N-acetylcysteine as well as the determined research of an external mycologist.In various retrospective studies, a relevant reduction of mortality could be shown by the mentioned medicinal measures. Despite the high estimated amount of ingestion, we could confirm the effectiveness of this combination therapy in this case.Here, in addition to the drug therapy, attention should also be paid to the extraordinary cooperation of a mycologist, who was able to confirm the suspected diagnosis by his investigative approach and thus contributed to the success of the therapy. Immediate contact with the competent poison centre and the involvement of an expert is therefore recommended in unclear situations.

Na+ /H+ exchanger NHE1 is active at cell-cell contacts and facilitates cell dissemination during collective migration of melanoma cells.

Tumour cell detachment from the primary tumour is an early and crucial step of the metastatic cascade. At the single cell level, it was already shown that migrating melanoma cells establish both intra- and extracellular pH gradients and that the Na+ /H+ exchanger NHE1 accumulates at the leading edges to strengthen cell-matrix interactions. However, less is known about the role of NHE1 in collective cell migration and the specific pH microenvironment at tumour cell-cell contacts. We used MV3 melanoma cells transfected with a NHE1-expressing vector or a control vector. NHE1 localization at cell-cell contacts was assessed via immunofluorescence imaging. Collective migration was analysed by live-cell imaging. The NHE1 activity and the perimembranous pH were measured both intra- and extracellularly by ratiometric fluorescence microscopy. NHE1 clearly localizes at cell-cell contacts. Its overexpression further increases migratory speed and translocation in multidirectional pathway analyses. NHE1 overexpressing MV3 cells also move further away from their neighbouring cells during wound closure assays. pH measurements revealed that the NHE1 is highly active at cell-cell contacts of melanoma cells. NHE1-mediated pH dynamics at such contact sites are more prominent in NHE1-overexpressing melanoma cells. Our findings highlight the contribution of the NHE1 towards modulation and plasticity of melanoma cell-cell contacts. We propose that its localization and functional activity at cell-cell contacts promotes evasion of single melanoma cells from the primary tumour.

Velocity Estimation from LiDAR Sensors Motion Distortion Effect.

Many modern automated vehicle sensor systems use light detection and ranging (LiDAR) sensors. The prevailing technology is scanning LiDAR, where a collimated laser beam illuminates objects sequentially point-by-point to capture 3D range data. In current systems, the point clouds from the LiDAR sensors are mainly used for object detection. To estimate the velocity of an object of interest (OoI) in the point cloud, the tracking of the object or sensor data fusion is needed. Scanning LiDAR sensors show the motion distortion effect, which occurs when objects have a relative velocity to the sensor. Often, this effect is filtered, by using sensor data fusion, to use an undistorted point cloud for object detection. In this study, we developed a method using an artificial neural network to estimate an object's velocity and direction of motion in the sensor's field of view (FoV) based on the motion distortion effect without any sensor data fusion. This network was trained and evaluated with a synthetic dataset featuring the motion distortion effect. With the method presented in this paper, one can estimate the velocity and direction of an OoI that moves independently from the sensor from a single point cloud using only one single sensor. The method achieves a root mean squared error (RMSE) of 0.1187 m s-1 and a two-sigma confidence interval of [-0.0008 m s-1, 0.0017 m s-1] for the axis-wise estimation of an object's relative velocity, and an RMSE of 0.0815 m s-1 and a two-sigma confidence interval of [0.0138 m s-1, 0.0170 m s-1] for the estimation of the resultant velocity. The extracted velocity information (4D-LiDAR) is available for motion prediction and object tracking and can lead to more reliable velocity data due to more redundancy for sensor data fusion.

Caffeine, lactic acid, or nothing: What effect does expectation have on men's performance and perceived exertion during an upper body muscular endurance task?

Objective: We tested the impact of subjects' belief in an ingested substance's ergogenic or ergolytic properties on muscular endurance performance and perceived exertion. Methods: Trained men (n = 15, age = 41 ± 4 y; body mass = 82.1 ± 15.8 kg; height = 173 ± 8 cm; experience = 7.4 ± 2.3 y) completed one set to failure at 80% repetition maximum of the bench press under three conditions. In all conditions, subjects ingested capsules of an identical, inert substance (300 mg cellulose), but, in a randomized order, subjects were told that they were either ingesting caffeine (Placebo), lactic acid (Nocebo), or cellulose (Control) and received information on the respective alleged ergogenic/ergolytic/neutral effects of each. Repetitions completed and rating of perceived exertion (RPE) were recorded. The data were analyzed among conditions using a Friedman test with post hoc analyses accomplished through Durbin-Conover tests. Spearman correlations were used to compare repetitions performed and RPE between Nocebo and Placebo conditions. Statistical significance was set at P ≤ 0.05. Results: Subjects lifted more (P < 0.001) repetitions in the Placebo condition (14.1 ± 3.0) versus Control (10.3 ± 2.9) or Nocebo (7.5 ± 2.6), while Control and Nocebo performances were similar (P = 0.192). Lower RPE was noted in Placebo versus Control (P = 0.003) and Nocebo (P < 0.001) and lower in Control versus Nocebo (P = 0.025). Subjects who performed more repetitions with Placebo tended to perform fewer repetitions under the Nocebo condition (Spearman's Rho =-0.578). Conclusion: This study believes that the ergogenic or ergolytic properties of a substance can measurably impact upper-body muscular endurance performance and RPE in trained men.

Pharmaceutical Interventions for Inpatients with Liver Cirrhosis and Liver Transplantation: A Systematic Review of Experimental Studies.

Liver cirrhosis, which is considered one of the leading causes of death in the world, can lead to severe complications, and is often followed by a liver transplantation. These patients take an average of nine medications daily. If not managed adequately, it can be accompanied by serious drug-related problems. To reduce this risk, a clinical pharmacist may be included as part of the healthcare team to optimize medication therapy in this population. This study aimed to systematically identify the pharmaceutical interventions which reduced drug-related problems and improved medication therapy for adult hospitalized liver cirrhotic and liver transplant patients when compared to standard care. Three databases (PubMed, Embase, and CENTRAL) were systematically searched from the inception of each database to 25 October 2023, and interventional studies in the English language were included. The risk of bias was assessed according to RoB-I for the UBA study and RoB2 for the identified RCT. The detected interventions to reduce drug-related problems in liver cirrhotic and liver transplant patients were extracted and classified according to a "Hierarchy of Controls" model. Two studies from Germany and the USA met our inclusion criteria, respectively. In these studies, we identified two interventions that included education, expert consultation, and the monitoring of the immunosuppressive medications serum level. The main objective of the two included studies was improving patients' compliance through adherence. These pharmaceutical interventions identified were classified as administrative controls, which is one of the lowest levels in the "Hierarchy of Controls" with which to address a potential risk. Pharmaceutical interventions to optimize medication therapy were found to be rare in the examined population, and were limited to "administrative controls". These interventions were limited to transplant patients' education and the monitoring of the immunosuppressive medication serum levels. No interventional studies were found to have investigated pharmaceutical interventions in patients with liver cirrhosis. Especially regarding this patient group, future studies to reduce DRPs using pharmaceutical interventions are needed. This study received no external funding and its PROSPERO registration number is CRD42022309122.