The impact of surgical timing on outcome in acute appendicitis in adults - a retrospective observational Population-Based cohort study.

BACKGROUND: Acute appendicitis is a global disease with high incidence. The main objective was to assess the association between time from admission to surgery (TAS) and surgery during emergency hours with operative outcome in light of conflicting evidence. METHODS: This is a retrospective population-wide analysis of hospital billing data (2010-2021) of all adult patient records of surgically treated cases of acute appendicitis in Germany by TAS. The primary outcome was a composite clinical endpoint (CCE; prolonged length of stay, surgical site infection, interventional draining after surgery, revision surgery, intensive care unit admission and/or in-hospital mortality). Cases of complicated appendicitis were identified using diagnosis (ICD-10) and procedural codes (resection beyond appendectomy). RESULTS: 855,694 patient records were included, of which 27·6% (236,481) were complicated cases of acute appendicitis. 49·0% (418,821) were females and median age was 37 (interquartile range 22·5-51·5). Age, male sex, and comorbidity were associated with an increased proportion of CCE and in-hospital mortality. TAS was associated with a clinically relevant increase of CCE after 12 hours in complicated appendicitis (Odd's Ratio, OR, 1·19, 95% Confidence Interval, CI, 1·14-1·21) and after 24 hours in uncomplicated appendicitis (OR 1·10, CI 1·02-1·19). Beyond the primary endpoint, the proportion of complicated appendicitis increased after TAS of 72 hours. Surgery during emergency hours (6 pm - 6.59 am) was associated with an increase of CCE and mortality (OR between 1·14 and 1·49). Age, female sex, nighttime admission, weekend admission, a known previous surgery, obesity, and therapeutic anticoagulation were associated with delayed performance of surgery. CONCLUSION: This work found an increase of a CCE after TAS of 12 hours for complicated appendicitis and an increase of the CCE after TAS of 24 hours for uncomplicated appendicitis with a stable proportion of complicated appendicitis in these time windows. Both CCE and mortality were increased if appendectomy was performed during emergency hours.

The Apparent Diffusion Coefficient of the Paraspinal and Psoas Muscles Are of Prognostic Relevance in Patients With Hepatocellular Carcinoma Undergoing Transarterial Radioembolization.

Background/Aim: Transarterial radioembolization (TARE) is a treatment option for early or intermediate stage hepatocellular carcinoma (HCC). Sarcopenia is defined as loss of muscle strength and quality which can be estimated by imaging modalities and has been associated with prognosis and treatment response in HCC patients. Apparent diffusion coefficient (ADC) values derived from diffusion-weighted imaging (DWI) can reflect the tissue composition and might be better to determine muscle changes of sarcopenia than the standard method of computed tomography (CT). The present study sought to elucidate ADC values of the abdominal wall muscles as a prognostic factor in patients undergoing TARE. Patients and Methods: A retrospective analysis was performed between 2016 and 2020. Overall, 52 patients, 9 women (17.3%) and 43 men (82.7%), with a mean age of 69±8.5 years were included into the analysis. In every case, the first pre-interventional magnetic resonance imaging (MRI) including DWI was used to measure the ADC values of paraspinal and psoas muscle. The 12-month survival after TARE was used as the primary study outcome. Results: Overall, 40 patients (76.9%) of the patient cohort died within the 12-month observation period. Mean overall survival was 10.9 months after TARE for all patients. Mean ADC values for all muscles were 1.31±0.13×10-3mm2/s. The ADC values of the paraspinal muscles were statistically significantly higher compared to the ADC values of the psoas muscles (p=0.0031). A positive correlation was identified between mean ADC and the thrombocyte count (r=0.37, p=0.005) and serum bilirubin (r=-0.30, p=0.03). In the multivariate Cox regression analysis, the mean ADC values of all muscles were associated with the survival after 12 months (HR=0.98, 95% CI=0.97-0.99, p=0.04). Conclusion: ADC values of the abdominal wall muscles could be used as a prognostic biomarker in patients with HCC undergoing TARE. These preliminary results should be confirmed by further studies using external validation cohorts and other treatment modalities.

Portal venous contrast enhancement ratio of the adrenal glands and spleen as prognostic marker of mortality in patients with acute mesenteric ischemia.

PURPOSE: Contrast enhancement of the adrenal gland defined by computed tomography (CT) was previously analyzed as a prognostic factor for critically ill patients in various diseases. However, no study investigated this quantitative parameter in patients with acute mesenteric ischemia. Therefore, the aim of this study was to evaluate the prognostic value of the contrast enhancement of the adrenal glands in patients with clinically suspected AMI. METHODS: All patients with clinically suspected AMI were retrospectively assessed between 2016 and 2020. All patients underwent surgical exploration after CT imaging. Overall, 134 patients (52 female patients, 38.8%) with a mean age of 69.2 ± 12.4 years were included into the present analysis. For all patients, the preoperative CT was used to calculate the contrast media enhancement of the adrenal glands and the spleen. RESULTS: A total of 27 patients (18.5%) died within the first 24 h and over the following 30-day 94 patients (68.6%) died. There were statistically significant differences regarding the mean values for adrenal-to-spleen ratio for 24-h mortality (p = 0.001) and 30-day mortality (p = 0.004), whereas the radiodensity of the inferior vena cava and the radiodensity of the spleen was statistically significant between survivors and non-survivors after 30 days (p = 0.037 and p = 0.028, respectively). In Cox regression analysis, mean adrenal radiodensity was associated with 24-h mortality (HR 1.09, 95% CI 1.02-1.16, p = 0.01) but not with 30-day mortality (HR 1.03, 95% CI 0.99-1.07, p = 0.13). CONCLUSION: The contrast media enhancement of the adrenal gland is associated with the 24-h and 30-day mortality in patients with AMI. However, the prognostic relevance for translation into clinical routine needs to be validated in other cohorts.

The GALAD score and the BALAD-2 score correlate with transarterial and systemic treatment response and survival in patients with hepatocellular carcinoma.

PURPOSE: The GALAD score and the BALAD-2 score are biomarker-based scoring systems used to detect hepatocellular carcinoma (HCC). Both incorporate levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Our objective was to examine the relationship between the GALAD score as well as the BALAD-2 score and treatment response to transarterial or systemic treatments in patients with HCC. METHODS: A total of 220 patients with HCC treated with either transarterial (n = 121) or systemic treatments (n = 99; mainly Sorafenib) were retrospectively analyzed. The GALAD score and the BALAD-2 score were calculated based on AFP-L3, AFP, and DCP levels measured in serum samples collected before treatment. The results were correlated with 3-month treatment efficacy based on radiologic mRECIST criteria. RESULTS: The GALAD score showed a strong correlation with BCLC stage (p < 0.001) and total tumor diameter before treatment (p < 0.001).The GALAD score at baseline was significantly lower in patients with a 3-month response to transarterial (p > 0.001) than in refractory patients. Among patients receiving systemic treatment, the median BALAD-2 score at baseline showed a strong association with response at month 3 (p < 0.001). In the transarterial treatment group, the GALAD score (AUC = 0.715; p < 0.001) as well as the BALAD score (AUC = 0.696; p < 0.001) were associated with overall survival, hereby outperforming AFP, AFP-L3 and DCP. CONCLUSION: The GALAD score as well as the BALAD-2 score hold significant promise as a prognostic tool for patients with early or intermediate-stage HCC who are undergoing transarterial or systemic treatments.

Basal MET phosphorylation is an indicator of hepatocyte dysregulation in liver disease.

Chronic liver diseases are worldwide on the rise. Due to the rapidly increasing incidence, in particular in Western countries, metabolic dysfunction-associated steatotic liver disease (MASLD) is gaining importance as the disease can develop into hepatocellular carcinoma. Lipid accumulation in hepatocytes has been identified as the characteristic structural change in MASLD development, but molecular mechanisms responsible for disease progression remained unresolved. Here, we uncover in primary hepatocytes from a preclinical model fed with a Western diet (WD) an increased basal MET phosphorylation and a strong downregulation of the PI3K-AKT pathway. Dynamic pathway modeling of hepatocyte growth factor (HGF) signal transduction combined with global proteomics identifies that an elevated basal MET phosphorylation rate is the main driver of altered signaling leading to increased proliferation of WD-hepatocytes. Model-adaptation to patient-derived hepatocytes reveal patient-specific variability in basal MET phosphorylation, which correlates with patient outcome after liver surgery. Thus, dysregulated basal MET phosphorylation could be an indicator for the health status of the liver and thereby inform on the risk of a patient to suffer from liver failure after surgery.

Analysis of Periprocedural X-ray Exposure in Transarterial Radioembolization with Glass or Resin Microspheres.

Background: Transarterial Radioembolization (TARE) is an effective treatment option for both primary and secondary liver malignancies. However, challenging anatomical conditions can lead to prolonged fluoroscopy times (FT), elevated doses of periprocedural X-radiation (DAP), and increased use of contrast agents (CAs). In this study, we examined the influence of our radiologists' experience and the choice of microspheres on X-ray exposure and CA doses in TARE. Material and Methods: Datasets comprising 161 TARE and 164 preprocedural evaluation angiographies (TARE-EVA) were analyzed. Our study focused on assessing DAP, FT, and CA concerning both microsphere types, the radiologist's experience, and whether the same radiologist performed both the TARE-EVA and the actual TARE. Results: In TARE, the use of resin microspheres resulted in significantly higher FT and CA compared to glass microspheres (14.3 ± 1.6 min vs. 10.6 ± 1.1 min and 43 ± 2.2 mL vs. 33.6 ± 2.1 mL, p < 0.05), with no notable differences in DAP (p = 0.13). Experienced radiologists demonstrated reduced FT/DAP, with a 19% decrease in DAP and 53% in FT during the evaluation angiography (p < 0.05) and a 49% reduction in DAP during the actual TARE (p < 0.05), with no statistical differences in FT. Performing TARE and TARE-EVA under the same radiologist led to a 43% reduction in DAP and a 25% decrease in FT (p < 0.05, respectively). Conclusions: To mitigate X-radiation exposure, it is advisable for radiologists to undergo thorough training, and, ideally, the same radiologist should conduct both the TARE and the TARE-EVA. While the use of glass spheres may decrease intraarterial CA, it does not significantly impact periprocedural X-ray exposure.

Diverticulitis patient care during the Covid-19 pandemic in Germany-a retrospective nationwide population-based cohort study.

PURPOSE: Coronavirus disease 2019 (COVID-19) impacted health care systems around the world. Despite a decrease in emergency admissions, an increased number of complicated forms of diverticulitis was reported. It was the aim of this study to analyze the pandemic impact on diverticulitis management in Germany. METHODS: This is a retrospective population-wide analysis of hospital billing data (2012-2021) of diverticulitis in Germany. Patients were identified based on diagnosis (ICD10) and procedural codes to stratify by conservative and operative management. Primary outcome of interest was admission rates, secondary outcomes were rates of surgical vs conservative treatment and fraction of complicated clinical courses during the pandemic. RESULTS: Of a total of 991,579 cases, 66,424 (6.7%) were admitted during pandemic lockdowns. Conservative treatment was the most common overall (66.9%) and higher during lockdowns (70.7%). Overall admissions and population adjusted rates of surgically treated patients decreased, the latter by 12.7% and 11.3%, corrected to estimated rates, in the two lockdowns. Surgery after emergency presentation decreased by 7.1% (p=0.053) and 11.1% (p=0.002) in the two lockdowns with a higher rate of ostomy and/or revision (+5.6%, p=0.219, and +10.2%, p=0.030). In-hospital mortality was increased in lockdown periods (1.64% vs 1.49%). In detail, mortality was identical in case of conservative treatment during lockdown periods (0.5%) but was higher in surgically treated patients (4.4% vs 3.6%). CONCLUSION: During lockdowns, there was an overall decrease of admissions for diverticulitis, especially non-emergency admissions in Germany, and treatment was more likely to be conservative. In case of surgery, however, there was increased risk of a complicated course (ostomy, re-surgery), possibly due to patient selection.

CT Texture Analysis and Node-RADS CT Score of Lymph Nodes in Patients With Perihilar Cholangiocarcinoma.

BACKGROUND/AIM: Texture analysis can provide quantitative imaging markers from computed tomography (CT) images. The Node-RADS classification was recently published as a classification system to better characterize lymph nodes in oncological imaging. The present analysis investigated the diagnostic benefit of CT texture analysis and the Node-RADS classification to categorize and stage lymph nodes in patients with perihilar cholangiocarcinoma. PATIENTS AND METHODS: Overall, 25 patients (n=9 females, 36%) with a mean age of 72.4±8.1 years were included. All patients were surgically resected and the lymph nodes were histopathologically analyzed. CT-texture analysis was performed with the Mazda package. All investigated lymph nodes were scored in accordance with the Node-RADS classification. RESULTS: Regarding lymph node discrimination (N- versus N+), Node-RADS classification achieved an area under the curve (AUC) of 0.86 resulting in a sensitivity of 78% and a specificity of 86%. Multiple investigated texture features were different between negative and positive lymph nodes. The "S(0,1)SumVarnc" achieved the best AUC of 0.75 resulting in a sensitivity of 0.91 and a specificity of 0.67. Correlation analysis showed various statistically significant associations between CT texture features and Node-RADS score. CONCLUSION: Several CT texture features and the Node-RADS score derived from preoperative staging CT were associated with the malignancy of the hilar lymph nodes and might aid for preoperative staging. This could change surgical treatment planning in hilar cholangiocarcinoma.

SARS-CoV-2 mRNA vaccination-induced immunological memory in human nonlymphoid and lymphoid tissues.

Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination have not been comprehensively analyzed in humans. We therefore studied SARS-CoV-2 mRNA vaccine-specific T cells in surgery specimens of kidney, liver, lung, bone marrow, and spleen compared with paired blood samples from largely virus-naive individuals. As opposed to lymphoid tissues, nonlymphoid organs harbored significantly elevated frequencies of spike-specific CD4+ T cells compared with blood showing hallmarks of tissue residency and an expanded memory pool. Organ-derived CD4+ T cells further exhibited increased polyfunctionality over those detected in blood. Single-cell RNA-Seq together with T cell receptor repertoire analysis indicated that the clonotype rather than organ origin is a major determinant of transcriptomic state in vaccine-specific CD4+ T cells. In summary, our data demonstrate that SARS-CoV-2 vaccination entails acquisition of tissue memory and residency features in organs distant from the inoculation site, thereby contributing to our understanding of how local tissue protection might be accomplished.

Old Age and Frailty in Deceased Organ Transplantation and Allocation-A Plea for Geriatric Assessment and Prehabilitation.

Due to demographic ageing and medical progress, the number and proportion of older organ donors and recipients is increasing. At the same time, the medical and ethical significance of ageing and old age for organ transplantation needs clarification. Advanced age is associated with the frailty syndrome that has a negative impact on the success of organ transplantation. However, there is emerging evidence that frailty can be modified by suitable prehabilitation measures. Against this backdrop, we argue that decision making about access to the transplant waiting list and the allocation of donor organs should integrate geriatric expertise in order to assess and manage frailty and impairments in functional capacity. Prehabilitation should be implemented as a new strategy for pre-operative conditioning of older risk patients' functional capacity. From an ethical point of view, advanced chronological age per se should not preclude the indication for organ transplantation and the allocation of donor organs.

Effect of Pre-Transplant Recipient Underweight on the Postoperative Outcome and Graft Survival in Primary Kidney Transplantation.

BACKGROUND: The objective of this study was to evaluate the influence of recipient underweight on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). PATIENTS AND METHODS: Three hundred thirty-three patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into underweight (BMI <18.5 kg/m2; N = 29) and normal weight (BMI 18.5-24.9 kg/m2; N = 304) groups. Clinicopathological characteristics, postoperative outcomes, and graft and patient survival were analyzed retrospectively. RESULTS: The postoperative rate of surgical complications and renal function were comparable between the groups. One year and 3 years after KT, 70% and 92.9%, respectively, of the pre-transplant underweight patients reached a normal BMI (≥18.5 kg/m2). The mean death-censored graft survival was significantly lower in pre-transplant underweight patients than in pre-transplant normal-weight patients (11.5 ± 1.6 years vs 16.3 ± 0.6 years, respectively; P = .045). Especially KT recipients with a moderate or severe pre-transplant underweight (BMI <17 kg/m2; N = 8) showed an increased rate of graft loss (5- and 10-year graft survival: 21.4% each). No statistical difference could be observed between the 2 groups regarding causes of graft loss. In multivariate analysis, recipient underweight (P = .024) remained an independent prognostic factor for graft survival. CONCLUSION: Being underweight did not affect the early postoperative outcome after primary KT. However, underweight, and especially moderate and severe thinness, is associated with reduced long-term kidney graft survival, and therefore this group of patients should be monitored with special attention.

Revising the MELD Score to Address Sex-Bias in Liver Transplant Prioritization for a German Cohort.

(1) Background: Prioritization of patients for liver transplantation in Germany relies on the MELD (model for end-stage liver disease) scoring system that does not consider the patient's sex. Many studies have shown that women are disadvantaged by the MELD score. Using a large patient cohort from a German liver transplant centre, we investigated options to reduce gender inequality in the patient prioritization for liver transplantation. (2) Methods: We calculated female-as-male MELD scores in our cohort by substituting the serum creatinine of a female patient with that of their male equivalent to test for the fairness of the scores. We investigated the effects of the female-as-male scores compared to the original MELD score of 1759 patients listed for liver transplantation. (3) Results: Serum creatinine sex correction (female-as-male) for MELD scores added up to 5.4 points in females, while the median changed by +1.6 points for females. We identified 72 females with an original MELD score < 20, for whom the adjusted female-as-male MELD score would be >20, thus giving them a better chance to receive a liver transplant. (4) Conclusions: Mathematical conversion of female to male creatinine concentrations identified disadvantages in liver transplantation prioritization for females and ascertained MELD 3.0 as having high potential to compensate for these inequalities.