Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis.

OBJECTIVE: Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission. DESIGN: Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated. RESULTS: After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP. CONCLUSIONS: The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts. TRIAL REGISTRATION NUMBER: NCT04777812.

A critical perspective on institutional violence against hospitalized children: Testimonies by health professionals and family members.

The purpose of this study is to understand institutional violence (IV) in the relationships between health professionals, hospitalized children, and family members. This is a qualitative study developed at the pediatric inpatient unit of a university hospital in the city of Salvador, Bahia, Brazil. The research participants consisted of 39 health professionals who specialized in pediatrics and 10 family members of hospitalized children. Semi-structured interviews were the method used for data collection. Using discourse analysis as a basis and taking a Foucauldian perspective, the researchers observed that the expressions of IV could be traced to abusive power relations within the system. We found four discursive forms within the data set: communication problems as IV, violence through inattention and neglect, violence as an action and consequent materialization on the body, and psychological violence as a submission mechanism. Based on these findings, we argue that professionals, managers, the scientific community, and users might be able to better guarantee the safety of children by recognizing IV and effectively intervening in it.

Discourse and manipulation: Nursing in question.

The history of Brazilian nurses is marked by several challenges, in part resulting from discontinuous and fragile activity boundaries among the health professions that share the same work objective in care services. A field of constant disputes, the Brazilian health system, was the target of a lawsuit filed by the Federal Council of Medicine that temporarily suspended nurses' activities in primary care. This study aimed to demonstrate the manipulative discourse present in the text of the injunction request by medical doctors against legislation by the Brazilian Federal Government in 2017. This is a qualitative and documental study that used the theoretical-methodological framework of critical discourse studies based on Teun Van Dijk's analytical categories. The results pointed to manipulative discourse through a polarization between manipulators' good qualities and intentions and the bad qualities of nurses and Brazilian primary care policies; episodic manipulation by the presentation of documental and historical evidence of the submission of nursing roles; and social manipulation marked by strong emotional appeal. The study demonstrated that manipulative discourse extrapolated linguistic categories in the form of ideology and history.

Design and validation of a patient-reported outcome measure scale in acute pancreatitis: the PAN-PROMISE study.

OBJECTIVE: This study aimed to develop and validate a patient-reported outcome measure (PROM) in acute pancreatitis (AP) as an endpoint centred on the patient. DESIGN: A PROM instrument (PAtieNt-rePoRted OutcoMe scale in acute pancreatItis, an international proSpEctive cohort study, PAN-PROMISE scale) was designed based on the opinion of patients, professionals and an expert panel. The scale was validated in an international multicentre prospective cohort study, describing the severity of AP and quality of life at 15 days after discharge as the main variables for validation. The COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) methodology was applied. Both the design and validation stages considered the content and face validity of this new instrument; the metric properties of the different items, reliability (reproducibility and internal consistence), the construct, structural and criterion validity, responsiveness and interpretability of this scale. RESULTS: PAN-PROMISE consists of a seven-item scale based on the symptoms that cause the most discomfort and concern to patients with AP. The validation cohort involved 15 countries, 524 patients. The intensity of symptoms changed from higher values during the first 24 hours to lower values at discharge and 15 days thereafter. Items converged into a unidimensional ordinal scale with good fit indices. Internal consistency and split-half reliability at discharge were adequate. Reproducibility was confirmed using test-retest reliability and comparing the PAN-PROMISE score at discharge and 15 days after discharge. Evidence is also provided for the convergent-discriminant and empirical validity of the scale. CONCLUSION: The PAN-PROMISE scale is a useful tool to be used as an endpoint in clinical trials, and to quantify patient well-being during the hospital admission and follow-up. TRIAL REGISTRATION NUMBER: NCT03650062.

Preoperative color Doppler ultrasound parameters for surgical decision-making in upper arm arteriovenous fistula maturation.

OBJECTIVE: Current scientific evidence is insufficient to determine the best vascular access for each patient. It is an unmet clinical need because vascular access dysfunction accounts for 20% to 30% of hospital admissions. Our aim was to evaluate preoperative color flow Doppler ultrasound (CDUS)-derived parameters (vein diameter and brachial artery flow and diameter) and their effect interaction with comorbidities as predictors of brachiocephalic (BC) and brachiobasilic (BB) arteriovenous fistula (AVF) maturation. METHODS: A prospective analysis was performed of patients who underwent BC and BB AVF as primary definitive vascular access between January 2016 and May 2017. Variables included patients' demographics, comorbidities, medication, preoperative blood pressure, and CDUS-derived parameters. Outcomes were patency 48 hours after surgery and fistula maturation at 6 and 12 weeks. Nonparametric descriptive and univariate statistics were used. Logistic regression models and receiver operating characteristic curve analyses were performed. RESULTS: There were 132 patients (91 with BC AVF and 41 with BB AVF) included. The 48-hour patency was 91.7%. AVF maturation at 6 weeks was observed in 71.3%, and AVF maturation at 12 weeks was observed in 66.3%. There were no associations in univariate and multivariate logistic regression analysis between AVF maturation and comorbidities. Systolic blood pressure was an independent predictor of 48-hour patency with an optimized cutoff of 154 mm Hg (area under the curve, 0.73; P = .013; Youden index, 0.40). Vein diameter with tourniquet was an independent predictor of AVF maturation at 6 and 12 weeks with an optimized cutoff of 3.9 mm (area under the curve, 0.74; P < .001; Youden index, 0.38). CONCLUSIONS: AVF maturation was independent of comorbidities. Systolic blood pressure ≥154 mm Hg and vein diameter with tourniquet ≥3.9 mm were the associated conditions that better predicted BC and BB AVF maturation. There were no effect interactions between CDUS-derived parameters and associated comorbidities.

On the utility of 3D hand cursors to explore medical volume datasets with a touchless interface.

Analyzing medical volume datasets requires interactive visualization so that users can extract anatomo-physiological information in real-time. Conventional volume rendering systems rely on 2D input devices, such as mice and keyboards, which are known to hamper 3D analysis as users often struggle to obtain the desired orientation that is only achieved after several attempts. In this paper, we address which 3D analysis tools are better performed with 3D hand cursors operating on a touchless interface comparatively to a 2D input devices running on a conventional WIMP interface. The main goals of this paper are to explore the capabilities of (simple) hand gestures to facilitate sterile manipulation of 3D medical data on a touchless interface, without resorting on wearables, and to evaluate the surgical feasibility of the proposed interface next to senior surgeons (N=5) and interns (N=2). To this end, we developed a touchless interface controlled via hand gestures and body postures to rapidly rotate and position medical volume images in three-dimensions, where each hand acts as an interactive 3D cursor. User studies were conducted with laypeople, while informal evaluation sessions were carried with senior surgeons, radiologists and professional biomedical engineers. Results demonstrate its usability as the proposed touchless interface improves spatial awareness and a more fluent interaction with the 3D volume than with traditional 2D input devices, as it requires lesser number of attempts to achieve the desired orientation by avoiding the composition of several cumulative rotations, which is typically necessary in WIMP interfaces. However, tasks requiring precision such as clipping plane visualization and tagging are best performed with mouse-based systems due to noise, incorrect gestures detection and problems in skeleton tracking that need to be addressed before tests in real medical environments might be performed.

Colorectal surgical mortality and morbidity in elderly patients: comparison of POSSUM, P-POSSUM, CR-POSSUM, and CR-BHOM.

PURPOSE: This study aims to compare the predictive value of POSSUM, P-POSSUM, CR-POSSUM and CR-BHOM in colorectal surgical mortality and morbidity in patients over 80 years old. METHODS: This is a retrospective observational longitudinal study. A total of 991 patients who underwent major colorectal surgery between 2008 and 2012 in a secondary hospital in Portugal were screened, and 204 who were over 80 years old were included. Subgroup analysis was performed for malignant/benign disease and emergent/elective surgery. The main outcome measure was 30-day postoperative mortality and morbidity with Clavien-Dindo classification ≥ 2. RESULTS: Of the 204 patients included in this study, 155 had malignant disease, and 65 underwent emergent procedures. Overall average age was 84.3 ± 3.9 years (range 80-100). Overall surgical mortality and morbidity were 18.6% (n = 38) and 52.4% (n = 87), respectively. Expected mortality followed the order P-POSSUM

Kaplan-Meier Survival Analysis: Practical Insights for Clinicians.

This article aims to provide a guide that will help healthcare professionals and clinical researchers from all fields that deal with Kaplan-Meier curves. Survival analysis methods are among the most frequently used in the medical sciences and in clinical research. Overall survival, progression free survival, time to recurrence, or any other clinically relevant parameter represented by a Kaplan-Meier curve will be discussed. We will present a practical and straightforward interpretation of these curves, setting aside intricate mathematical considerations. Our focus will be on essential concepts that interface with biological sciences and medicine in order to guarantee proficiency in one of the most popular yet frequently misunderstood methods in clinical research. Being familiar with these concepts is not only essential for designing new clinical studies but also for critically assessing and interpreting published data.

Zebrafish Avatar-test forecasts clinical response to chemotherapy in patients with colorectal cancer.

Cancer patients often undergo rounds of trial-and-error to find the most effective treatment because there is no test in the clinical practice for predicting therapy response. Here, we conduct a clinical study to validate the zebrafish patient-derived xenograft model (zAvatar) as a fast predictive platform for personalized treatment in colorectal cancer. zAvatars are generated with patient tumor cells, treated exactly with the same therapy as their corresponding patient and analyzed at single-cell resolution. By individually comparing the clinical responses of 55 patients with their zAvatar-test, we develop a decision tree model integrating tumor stage, zAvatar-apoptosis, and zAvatar-metastatic potential. This model accurately forecasts patient progression with 91% accuracy. Importantly, patients with a sensitive zAvatar-test exhibit longer progression-free survival compared to those with a resistant test. We propose the zAvatar-test as a rapid approach to guide clinical decisions, optimizing treatment options and improving the survival of cancer patients.

Routine Imaging or Symptomatic Follow-Up After Resection of Pancreatic Adenocarcinoma.

Importance: International guidelines lack consistency in their recommendations regarding routine imaging in the follow-up after pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). Consequently, follow-up strategies differ between centers worldwide. Objective: To compare clinical outcomes, including recurrence-focused treatment and survival, in patients with PDAC recurrence who received symptomatic follow-up or routine imaging after pancreatic resection in international centers affiliated with the European-African Hepato-Pancreato-Biliary Association (E-AHPBA). Design, Setting, and Participants: This was a prospective, international, cross-sectional study. Patients from a total of 33 E-AHPBA centers from 13 countries were included between 2020 and 2021. According to the predefined study protocol, patients who underwent PDAC resection and were diagnosed with disease recurrence were prospectively included. Patients were stratified according to postoperative follow-up strategy: symptomatic follow-up (ie, without routine imaging) or routine imaging. Exposures: Symptomatic follow-up or routine imaging in patients who underwent PDAC resection. Main Outcomes and Measures: Overall survival (OS) was estimated with Kaplan-Meier curves and compared using the log-rank test. To adjust for potential confounders, multivariable logistic regression was used to evaluate the association between follow-up strategy and recurrence-focused treatment. Multivariable Cox proportional hazard analysis was used to study the independent association between follow-up strategy and OS. Results: Overall, 333 patients (mean [SD] age, 65 [11] years; 184 male [55%]) with PDAC recurrence were included. Median (IQR) follow-up at time of analysis 2 years after inclusion of the last patient was 40 (30-58) months. Of the total cohort, 98 patients (29%) received symptomatic follow-up, and 235 patients (71%) received routine imaging. OS was 23 months (95% CI, 19-29 months) vs 28 months (95% CI, 24-30 months) in the groups who received symptomatic follow-up vs routine imaging, respectively (P = .01). Routine imaging was associated with receiving recurrence-focused treatment (adjusted odds ratio, 2.57; 95% CI, 1.22-5.41; P = .01) and prolonged OS (adjusted hazard ratio, 0.75; 95% CI, 0.56-.99; P = .04). Conclusion and Relevance: In this international, prospective, cross-sectional study, routine follow-up imaging after pancreatic resection for PDAC was independently associated with receiving recurrence-focused treatment and prolonged OS.

Discharge protocol in acute pancreatitis: an international survey and cohort analysis.

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care.

Spontaneous internal hernia through a defect in the hepatogastric ligament.

Transomental internal hernias are a rare cause of intestinal obstruction and most commonly iatrogenic, resulting from previous surgical interventions, abdominal trauma or inflammation. Occasionally, they may occur spontaneously. We report the case of a 44-year-old healthy male admitted to the emergency room with acute abdominal pain and vomiting, consistent with intestinal obstruction. An internal hernia of small bowel in the lesser sac was suspected after performing a computed tomography (CT) scan and emergent laparotomy confirmed herniation of a jejunal loop through a defect in the hepatogastric ligament, resulting in strangulation and requiring enterectomy. The patient had a favourable outcome and was discharged a few days after surgery. Both radiologists and surgeons must be aware of rare internal hernia subtypes, to avoid delays in diagnosis and treatment. Abdominal CT is the first-line imaging of choice, providing useful diagnostic hallmarks. Nevertheless, surgical exploration is typically essential to confirm the diagnosis, identify the defect and assess bowel viability.

Inflammatory and nutritional biomarkers as predictors of non-resectability and early recurrence in pancreatic and periampullary cancer.

BACKGROUND: Some pancreatic tumors considered resectable on the preoperative staging are unresectable during surgical exploration. Moreover, some patients subjected to tumor resection have an early recurrence. METHODS: Patients with pancreatic or periampullary carcinoma diagnosed between January 2005 and August 2017 at the Prof. Doutor Fernando Fonseca Hospital were retrospectively analyzed. Biochemical and radiological inflammatory biomarkers were compared according to disease staging at diagnosis, intraoperative staging and early recurrence (<6 months). RESULTS: Three hundred ninety-one patients were included. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, C-reactive-protein-to-albuminemia ratio (CRP/ALB), Prognostic Nutritional Index, modified Glasgow Prognostic Score and CA19-9 were associated with metastatic disease at diagnosis. NLR, CRP/ALB, mGPS and CA19-9 were independent predictors of disease staging at diagnosis on multivariate analysis. One hundred eight patients underwent surgery, of which 23.8% were found to have unresectable disease at intra-operative staging. 26.9% had early disease recurrence. CRP/ALB and CA19-9 were significantly higher in patients with evidence of disease at 6 months postoperatively. Computed tomography sarcopenia index HUAC was significantly lower in patients with evidence of disease at 6 months postoperatively. When adjusted for histology, none of the biomarkers were independent predictors of unresectable disease or early recurrence. CONCLUSIONS: NLR, CRP/ALB, mGPS and CA19-9 at diagnosis were predictors of disease staging with low performance. Preoperative inflammatory biomarkers were not predictors of unresectable disease or early recurrence.

Chronic Kidney Disease-Mineral Bone Disease Biomarkers in Kidney Transplant Patients.

BACKGROUND: Kidney transplant patients frequently suffer from Chronic Kidney Disease associated with Mineral Bone Disease (CKD-MBD), a complex condition that affects mainly kidney transplant patients. Post-transplantation bone disease is complex, especially in patients with pre-existing metabolic bone disorders that are further affected by immunosuppressive medications and changes in renal allograft function. Main biochemical abnormalities of mineral metabolism in kidney transplantation (KTx) include hypophosphatemia, hyperparathyroidism (HPTH), insufficiency or deficiency of vitamin D, and hypercalcemia. OBJECTIVE: This review aims to summarize the pathophysiology and main biomarkers of CKD-MBD in KTx. METHODS: A comprehensive and non-systematic search in PubMed was independently made, emphasizing biomarkers in mineral bone disease in KTx. RESULTS: CKD-MBD can be associated with numerous factors, including secondary HPTH, metabolic dysregulations before KTx, and glucocorticoid therapy in post-transplant subjects. Fibroblast growth factor 23 (FGF23) reaches normal levels after KTx with good allograft function, while calcium, vitamin D, and phosphorus, ultimately result in hypercalcemia, persistent vitamin D insufficiency, and hypophosphatemia, respectively. As for PTH levels, there is an initial tendency of a significant decrease, followed by a rise due to secondary or tertiary HPTH. In regard to sclerostin levels, there is no consensus in the literature. CONCLUSION: KTx patients should be continuously evaluated for mineral homeostasis and bone status, both in cases with successful kidney transplantation and those with reduced functionality. Additional research on CKD-MBD pathophysiology, diagnosis, and management is essential to guarantee long-term graft function, better prognosis, good quality of life, and reduced mortality for KTx patients.

Zebrafish xenografts as a fast screening platform for bevacizumab cancer therapy.

Despite promising preclinical results, average response rates to anti-VEGF therapies, such as bevacizumab, are reduced for most cancers, while incurring in remarkable costs and side effects. Currently, there are no biomarkers available to select patients that can benefit from this therapy. Depending on the individual tumor, anti-VEGF therapies can either block or promote metastasis. In this context, an assay able to predict individual responses prior to treatment, including the impact on metastasis would prove of great value to guide treatment options. Here we show that zebrafish xenografts are able to reveal different responses to bevacizumab in just 4 days, evaluating not only individual tumor responses but also the impact on angiogenesis and micrometastasis. Importantly, we perform proof-of-concept experiments where clinical responses in patients were compared with their matching zebrafish Patient-Derived Xenografts - zAvatars, opening the possibility of using the zebrafish model to screen bevacizumab therapy in a personalized manner.

Ocotea glomerata (Nees) Mez Extract and Fractions: Chemical Characterization, Anti-Candida Activity and Related Mechanism of Action.

BACKGROUND: Opportunistic fungal infections are increasingly common, with Candida albicans being the most common etiological agent; however, in recent years, episodes of candidiasis caused by non-albicans Candida species have emerged. Plants belonging to the Lauraceae family have shown remarkable antifungal effects. This study assessed the anti-Candida activity of Ocotea glomerata extracts and fractions, time of death and the synergistic effects with conventional antifungals. The possible mechanism of action was also addressed. METHODS: Minimal inhibitory concentrations (MIC) were determined by broth microdilution technique, and the mechanism of action was assessed by ergosterol, sorbitol, cell viability, reactive oxygen species (ROS) generation and phosphatidylserine externalization tests. RESULTS: All the tested extracts evidenced antifungal activity, but the methanol extract was revealed to be the most effective (MIC = 3.12 µg/mL) on C. krusei. The combination of methanol extract with ketoconazole and fluconazole revealed a synergistic effect for C. krusei and C. albicans, respectively. Fractions 1 and 5 obtained from the methanol extract had fungicidal activity, mainly against C. krusei. Methanol extract did not reveal effects by ergosterol and sorbitol assays; however, it led to an increase in intracellular ROS levels, decreased cell viability, and consequently, cell death. CONCLUSION: O. glomerata methanol extract may be viewed as a rich source of biomolecules with antifungal activity against Candida spp.

Unclassified autoimmune pancreatitis mimicking pancreatic cancer.

A 24-year-old black male presented with a 1-week obstructive jaundice and intermittent abdominal pain, with no significant weight loss and an unsuspicious abdominal exam. Blood chemistry showed a cholestatic pattern but a complete immunological and tumoral panel (anti-smooth muscle antibody, anti-mitochondrial antibody, anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, anti-Smith, anti-double-stranded-DNA antibody (anti-dsDNA), complement C3/C4, carcinoembryonic antigen, CA 19-9 and IgG4) were all within normal limits. Abdominal ultrasound revealed dilatation of the intra and extra-hepatic bile ducts. CT scan showed an abnormal dilatation of the distal bile duct but no focal enlargement of the head of the pancreas. Endoscopic ultrasound suggested an inflammatory process but the magnetic resonance cholangio-pancreatography favored a neoplastic obstruction of the distal common bile duct. Fine-needle aspiration cytology was insufficient for definitive diagnosis and the patient underwent major surgery. Follow-up with mild exocrine pancreatic insufficiency treated with enzyme replacement.