Persistent Organ Research Articles

Decreased skeletal muscle density is an independent predictor of mortality in necrotizing pancreatitis- A single tertiary center experience in 507 patients

Background and aimsNecrotizing pancreatitis has a variable clinical course and it is essential to identify determinants associated with high risk of mortality and poor clinical outcomes. The aim of this study is to evaluate the association between CT-assessed body composition parameters such as visceral fat area (VFA), skeletal muscle index (SMI) and skeletal muscle density (SMD) and inpatient mortality in NP patients. Secondary outcomes include organ failure on admission, persistent organ failure, length of stay (LOS), need for ICU admission, need for endoscopic, percutaneous or surgical interventions for NP and 30-day unplanned readmission. MethodsAll NP patients managed at a single center between 2009 and 2019 with a CT scan within a week of admission were included. SMI, SMD and VFA was calculated from CT imaging at the third lumbar vertebra and multivariable analysis was performed after correcting for age, sex, BMI, ASA classification, multi- organ failure on admission to determine independent association with inpatient mortality and secondary outcomes. Results507 NP patients [males = 349 (68.8%), median age 53 (IQR 37–65) years were included in this study. The lowest tertile SMD was independently associated with inpatient mortality on multivariable analysis: adjusted OR 3.36 (1.57–7.2), P = 0.002. The lowest SMI tertile and highest VFA tertile were not independently associated with mortality. Lowest tertile SMD was significantly associated with persistent organ failure (OR 2.01, 95% CI 1.34–3.01, p = 0.001), need for percutaneous drainage (OR 1.84, 95% CI 1.21–2.8, p = 0.004), need for ICU admission (OR 2.32, 95% CI 1.59–3.38, p < 0.0001) and LOS. ConclusionLow SMD was independently associated with in-hospital mortality in NP patients and can be usefully incorporated in CT based predictive scoring models as a prognostic marker.

Assessment of severity of acute pancreatitis with bedside index for severity in acute pancreatitis (BISAP) score

Background: There are many multifactorial scoring systems, radiological scores and biochemical markers available for early prediction of severity and mortality in patients with acute pancreatitis(AP). The bedside index for severity in acute pancreatitis (BISAP) Score has been considered as an accurate method of risk stratification in patients with acute pancreatitis. Objective: To assess and classify patients with acute pancreatitis according to bedside index for severity in acute pancreatitis (BISAP) Score and to corelate the prognosis of the patients with the BISAP score. Methodology: Records of patients who are admitted with acute pancreatitis in Mandya Institute of Medical Sciences, Mandya between January 2018 and December 2019 (2 year period) was studied, 152 acute pancreatitis cases were admitted during this period. All the cases records were analysed. Those diagnosed with acute pancreatitis on the basis of epigastric pain, serum amylase and serum lipase levels more than 3 times normal were subjected to investigations for BISAP scoring. BISAP score was calculated at 24 hours. A score of > 3 was used to label severe acute pancreatitis(SAP) according to the scoring system. Statistical analysis was made using the student t test and chi-square test and statistical significance was analysed. Results: In our study Out of 152 patients, 26% had severe acute pancreatitis. Acute Pancreatitis was seen in male (78%), in 4th decade (65%), alcohol was the most common aetiology (52%), followed by biliary pancreatitis (33%), remaining idiopathic (15%). Patients with BISAP >= 3 was associated with transient or persistent organ failure and pancreatic necrosis. Accuracy to predict SAP by BISAP score was 63.3 %, on the basis of sensitivity. Conclusion: BISAP score is a valuable tool in classifying patients of Acute Pancreatitis for severity and for predicting the prognosis in early hours. Keywords: Acute pancreatitis, BISAP score pancreatic necrosis organ f

Occurrence and Risk Factors of Infected Pancreatic Necrosis in Intensive Care Unit–Treated Patients with Necrotizing Severe Acute Pancreatitis

BackgroundIn patients with severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN) is associated with a worsened outcome. We studied risk factors and consequences of IPN in patients with necrotizing SAP. MethodsThe study consisted of a retrospective cohort of 163 consecutive patients treated for necrotizing SAP at a university hospital intensive care unit (ICU) between 2010 and 2018. ResultsAll patients had experienced at least one persistent organ failure and approximately 60% had multiple organ failure within the first 24 h from admission to the ICU. Forty-seven (28.8%) patients had IPN within 90 days. Independent risk factors for IPN were more extensive anatomical spread of necrotic collections (unilateral paracolic or retromesenteric (OR 5.7, 95% CI 1.5–21.1) and widespread (OR 21.8, 95% CI 6.1–77.8)) compared to local collections around the pancreas, postinterventional pancreatitis (OR 13.5, 95% CI 2.4–76.5), preceding bacteremia (OR 4.8, 95% CI 1.3–17.6), and preceding open abdomen treatment for abdominal compartment syndrome (OR 3.6, 95% CI 1.4–9.3). Patients with IPN had longer ICU and overall hospital lengths of stay, higher risk for necrosectomy, and higher readmission rate to ICU. ConclusionsWide anatomical spread of necrotic collections, postinterventional etiology, preceding bacteremia, and preceding open abdomen treatment were identified as independent risk factors for IPN.

Stress Hyperglycemia Is Independently Associated with Persistent Organ Failure in Acute Pancreatitis

Background/AimsStress hyperglycemia is common in critical illness but it has not been clearly studied in patients with acute pancreatitis (AP). This study aimed to investigate the specific blood glucose (BG) level that defines stress hyperglycemia and to determine the impact of stress hyperglycemia on clinical outcomes in AP patients.MethodsAP patients admitted ≤ 48 h after abdominal pain onset were retrospectively analyzed. Patients were stratified by pre-existing diabetes and stress hyperglycemia was defined using stratified BG levels for non-diabetes and diabetes with clinical outcomes compared.ResultsThere were 967 non-diabetic and 114 diabetic (10.5%) patients met the inclusion criteria and the clinical outcomes between these two groups were not significantly different. In non-diabetes, the cut-off BG level of ≥ 180 mg/dl was selected to define stress hyperglycemia with an 8.8-fold higher odds ratio for persistent organ failure (POF) (95% CI 5.4–14.3; P < 0.001). For diabetes, ≥ 300 mg/dl was selected with a 7.5-fold higher odds ratio for POF (95% CI 1.7–34.3; P = 0.009). In multivariable logistic regression, stress hyperglycemia was independently associated with POF, acute necrotic collection, major infection and mortality. The combination of BG and systemic inflammatory response syndrome (SIRS) score in predicting POF was better than SIRS or Glasgow score alone.ConclusionsThis study identifies a cut-off BG level of ≥ 180 mg/dl and ≥ 300 mg/dl was optimal to define stress hyperglycemia for non-diabetic and diabetic AP patients, respectively. There was a significant relationship between stress hyperglycemia and adverse clinical outcomes.

Blood Leukocyte Signaling Pathways as Predictors of Severity of Acute Pancreatitis.

ObjectivesClinical practice lacks biomarkers to predict the severity of acute pancreatitis (AP). We studied if intracellular signaling of circulating leukocytes could predict persistent organ dysfunction (OD) and secondary infections in AP.MethodsA venous blood sample was taken from 174 patients with AP 72 hours or less from onset of symptoms and 31 healthy controls. Phosphorylation levels (p) of appropriately stimulated signal transducer and activator of transcription 1 (STAT1), STAT6, nuclear factor-κB (NF-κB), Akt, and nonstimulated STAT3 in monocytes, neutrophils, and lymphocytes was measured using phosphospecific flow cytometry.ResultsThe patients showed higher pSTAT3 and lower pSTAT1, pSTAT6, pNF-κB, and pAkt than healthy controls. pSTAT3 in all leukocyte subtypes studied increased, and pSTAT1 in monocytes and T cells decreased in an AP severity-wise manner. In patients without OD at sampling, high pSTAT3 in monocytes and T lymphocytes were associated with development of persistent OD. In patients with OD, low interleukin-4–stimulated pSTAT6 in monocytes and neutrophils and Escherichia coli–stimulated pNF-κB in neutrophils predicted OD persistence. High pSTAT3 in monocytes, CD8+ T cells, and neutrophils; low pSTAT1 in monocytes and T cells; and low pNF-κB in lymphocytes predicted secondary infections.ConclusionsLeukocyte STAT3, STAT1, STAT6, and NF-κΒ phosphorylations are potential predictors of AP severity.

A Novel 5-Cytokine Panel Outperforms Conventional Predictive Markers of Persistent Organ Failure in Acute Pancreatitis.

INTRODUCTION:Existing laboratory markers and clinical scoring systems have shown suboptimal accuracies for early prediction of persistent organ failure (POF) in acute pancreatitis (AP). We used information theory and machine learning to select the best-performing panel of circulating cytokines for predicting POF early in the disease course and performed verification of the cytokine panel's prognostic accuracy in an independent AP cohort.METHODS:The derivation cohort included 60 subjects with AP with early serum samples collected between 2007 and 2010. Twenty-five cytokines associated with an acute inflammatory response were ranked by computing the mutual information between their levels and the outcome of POF; 5 high-ranking cytokines were selected. These cytokines were subsequently measured in early serum samples of an independent prospective verification cohort of 133 patients (2012–2016), and the results were trained in a Random Forest classifier. Cross-validated performance metrics were compared with the predictive accuracies of conventional laboratory tests and clinical scores.RESULTS:Angiopoietin 2, hepatocyte growth factor, interleukin 8, resistin, and soluble tumor necrosis factor receptor 1A were the highest-ranking cytokines in the derivation cohort; each reflects a pathologic process relevant to POF. A Random Forest classifier trained the cytokine panel in the verification cohort and achieved a 10-fold cross-validated accuracy of 0.89 (area under the curve 0.91, positive predictive value 0.89, and negative predictive value 0.90), which outperformed individual cytokines, laboratory tests, and clinical scores (all P ≤ 0.006).DISCUSSION:We developed a 5-cytokine panel, which accurately predicts POF early in the disease process and significantly outperforms the prognostic accuracy of existing laboratory tests and clinical scores.

Acute-on-Chronic Pancreatitis: Analysis of Clinical Profile and Outcome.

Objective: Overall, a handful of studies are available on the outcomes of acute-on-chronic pancreatitis (ACP). We aimed to provide a more complete and updated picture of ACP.Methods: We evaluated consecutive patients of acute exacerbation of chronic pancreatitis (CP) in a tertiary care center located in north India and studied their epidemiological profiles, etiological factors as well as outcomes.Results: Forty-five patients of ACP with a mean age of 37±13 years were evaluated. The majority of the patients were male (75%) and alcohol was the most common detectable etiology while no etiology could be identified in 35% of patients after extensive laboratory investigations and imaging. Moderately severe pancreatitis was noted in 73% of patients and 49% of patients had necrotizing pancreatitis out of which the majority (33%) had both pancreatic as well as extra-pancreatic necrosis (EPN). Five patients (11%) were subjected to percutaneous catheter drainage. Persistent organ failure was noted in 9% of patients and two (4.5%) patients had died from organ failure.Conclusion: To conclude, this study has demonstrated that ACP has a milder disease course and low morbidity and mortality. Early elimination of the etiological factor is essential for optimal outcome.

Characterization of organic compounds and drugs in sewage sludge aiming for agricultural recycling

The application of sewage sludge in soils can bring benefits to agricultural productivity, however, the risks arising from this application must be measured and carefully evaluated. Persistent organics compounds and drugs can be present in the sewage sludge and if applied to the soil, they can cause severe risks to the soil biota and contamination of groundwater. This work determined 174 persistent organic compounds and drugs in sludge samples from a wastewater treatment plant using chromatographic methods. The drugs ciprofloxacin, enrofloxacin and diclofenac were quantified, and values varied according to sampling period. For persistent organic compounds, cresols were the most abundant compounds in sewage sludge. With the analyses made of both the elutriate and the filtrate, it was possible to verify the potential for soil retention or leaching that each compound can present with the application of sewage sludge in the agriculture.

Acute necrotising pancreatitis: measurements of necrosis volume and mean CT attenuation help early prediction of organ failure and need for intervention.

This study explored the early predictive value of volume and mean CT density of necrosis for adverse outcomes in patients with acute necrotising pancreatitis (ANP). A total of 155 patients with ANP who underwent CECT within 7 days of symptom onset were included. The necrosis volume, mean CT density, and modified CT severity index (mCTSI) were calculated. C-reactive protein (CRP) and blood urea nitrogen (BUN) levels both 48 h after symptom onset were reviewed. Adverse outcomes were recorded. The predictive value of each indicator was assessed using ROC curve analysis. There were significant associations between necrosis volume and mean CT density and organ failure (OF), persistent OF (POF), and need for intervention (p < 0.001 for all). For predicting OF, the area under the curve (AUC) was significantly higher for necrosis volume than for mCTSI and BUN (AUC: 0.84 vs 0.67, p = 0.0011; 0.84 vs 0.71, p = 0.0193, respectively). For predicting POF and need for intervention, the AUCs for necrosis volume were significantly higher than those for mCTSI (AUC: 0.79 vs 0.66, p = 0.0045; 0.77 vs 0.61, p = 0.0019, respectively), but did not significantly differ from those for CRP and BUN. For predicting OF, a significantly better predictive value was achieved with mean CT density than with mCTSI (AUC: 0.79 vs 0.67, p = 0.0163). There were no significant differences in predictive value between mean CT density, CRP, and BUN. The volume and mean CT density of necrosis based on CECT can provide early prediction of OF, POF, and need for intervention. • Compared to mCTSI, necrosis volume might be used to more accurately diagnose organ failure and persistent organ failure and might be better associated with the need for intervention. • Necrosis volume and mean CT density based on CECT are reliable quantitative predictors for organ failure, persistent organ failure, and intervention in acute pancreatitis.

Early on-demand drainage or standard management for acute pancreatitis patients with acute necrotic collections and persistent organ failure: A pilot randomized controlled trial.

The current standard care for acute pancreatitis with acute necrotic collections (ANC) is to postpone invasive intervention for 4 weeks when indicated. However, in patients with persistent organ failure (POF), this delayed approach may prolong organ failure. In this study, we aimed to assess the feasibility and safety of earlier drainage for acute pancreatitis patients with ANC and POF. A single-center, randomized controlled trial was conducted. Eligible patients were randomly assigned to either the early on-demand (EOD) group or the standard management (SM) group. Within 21days of randomization, early drainage was triggered by unremitted or worsening organ failure in the EOD group. The primary endpoint was a composite of major complications/death during 90-days follow-up. Thirty patients were randomized. Within 21days of randomization, eight of the 15 patients (53%) in the EOD group underwent percutaneous drainage compared to four of the 15 patients (27%) in the SM group (P=0.26). The primary outcome occurred in three of the 15 (20%) patients in the EOD group and seven of the 15(46.7%) in the controls (P=0.25, relative risk 0.43, 95%CI 0.14 to 1.35). Although the EOD approach did not result in significant differences between groups, the primary outcome assessed in this trial demonstrated the potential for clinical benefits favoring early drainage.

Paediatric multisystem inflammatory syndrome in a ten-year old boy in a resource limited setting: a case for locally developed diagnostic criteria

Paediatric multisystem inflammatory syndrome (PMIS) occurs two to four weeks following exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus 2019 (COVID-19). It is characterized by the presence of persistent fever, inflammation and organ dysfunction. We present AE a 10-year old Nigerian boy who presented to the children emergency room with a history of continuous and high grade fever with back and multiple joint pains. While on admission he developed cough, difficulty with breathing, bleeding from the gums and altered consciousness which progressed to loss of consciousness. Complete blood count showed neutrophilia of 82.9%, lymphopenia of 9.8%, thrombocytopenia of 142,000 cells/mm3, elevated erythrocyte sedimentation rate of 75mm/hr, chest radiograph findings of ground glass appearance and consolidation in all lung lobes bilaterally with a positive reverse transcriptase-polymerase chain reaction test for COVID-19 which met the Centre for Disease Control criteria for the diagnosis of pediatric multisystem inflammatory syndrome. The patient was treated with intranasal oxygen, transfused with fresh whole blood, analgesics and antifailure drugs. His condition however deteriorated while on admission and died on the seven days of admission.

Portable wastewater treatment system based on synergistic photocatalytic and persulphate degradation under visible light

Highly efficient, low-cost, and portable wastewater treatment and purification solutions are urgently needed for aqueous pollution removal, especially at remote sites. Synergistic photocatalytic (PC) and persulphate (PS) degradation under visible light offers an exceptional alternative for this purpose. In this work, we coupled a TiO2-based PC system with a PS oxidation system into a portable advanced oxidation device for rapid and deep degradation of organic contaminants in wastewater. Using hydrogenation, we fabricated hydrogenated anatase branched-rutile TiO2 nanorod (H-AB@RTNR) photocatalysts which enable the PC degradation to occur under visible light and improve the utilization of solar energy. We also discovered that the addition of PS resulted in the synergistic degradation of tenacious and persistent organics, dramatically improving the extent and kinetics of the degradation. A degradation rate of 100% and a reaction rate constant of 0.0221 min−1 for degrading 1 L rhodamine B (20 mg L−1) were achieved in 120 min in a specially designed thin-layer cell under visible light irradiation. The superior performance of the synergistic PC and PS degradation system was also demonstrated in the degradation of real industrial wastewater. Both remarkable performances can be attributed to the heterophase junction and oxygen vacancies in the photocatalyst that facilitate the catalytic conversion of PS anions into highly active radicals (·SO4− and ·OH). This work suggests that the as proposed synergistic degradation design is a promising solution for building a portable wastewater treatment system.

Adjunctive branch interventions during thoracic endovascular aortic repair for acute complicated type B dissection are not associated with inferior outcomes

ObjectiveThoracic endovascular aortic repair (TEVAR) has been shown to effectively treat malperfusion associated with acute type B thoracic aortic dissection (TBAD). A subset of patients might still require adjunctive peripheral or visceral artery branch interventions during TEVAR to remedy persistent end organ malperfusion. Our objectives were to determine the incidence of these adjunctive interventions and to compare the outcomes between patients who had and had not undergone such interventions. MethodsWe performed a retrospective review of the TEVAR and complex EVAR module of the Vascular Quality Initiative from 2010 to 2019 to identify all patients treated for malperfusion due to acute TBAD. The anatomic branch and procedure performed at TEVAR were recorded. The 30-day mortality, need for reintervention, complication rates, and overall survival were compared between these patients stratified by adjunctive intervention status. ResultsA total of 426 patients had undergone TEVAR for acute TBAD with end organ malperfusion. Of the 426 patients, 126 (29.6%) had undergone 182 adjunctive branch interventions during TEVAR. The most common interventions were stenting (n = 86; 47.3%) and stent grafting (n = 49; 26.9%), with the most common site being the left renal artery (n = 49; 26.9%). The patients in both groups had similar 30-day mortality (12.4% with branch intervention vs 15.6% without; P = .511) and rates of in-hospital reintervention (19.2% with branch intervention vs 20.7% without; P = .732). No differences were found in the rates of postoperative complications or overall survival at 3 years between the two groups. ConclusionsAdjunctive peripheral and visceral artery branch interventions in conjunction with TEVAR for acute TBAD with malperfusion occurred in one third of index cases, but did not predispose patients to worse overall outcomes. Adjunctive arterial branch interventions should be included in the treatment paradigm for acute TBAD with end organ malperfusion that does not improve with primary entry tear coverage alone.

Nutrition support in the chronic critically ill patients

Over the last decade, chronic critically ill (CCI) has emerged as an epidemic in intensive care unit (ICU) survivors worldwide. Advances in ICU technology and implementation of care bundles has significantly decreased early deaths of critically ill patients, and have allowed them to survive previously lethal multiple organ failure (MOF). However, more and more survivors leave persistent low grade organ dysfunctions, depend on continues organ support, need to stay in ICU, and become CCI patients. These patients experience a persistent immune dysregulation with persistent inflammation, immunosuppression, and catabolic syndrome. Therefore, malnutrition is an important feature of patients with CCI, and nutritional support is a crucial part of their treatment. The main strategies of nutritional support are as follows: providing sufficient calories and proteins with appropriate anabolic agents to promote anabolic metabolism, using immunomodulators to improve immune suppression and inflammatory responses, and supplementing micronutrients to enhance metabolic support. In this review, the nutritional assessment, calorie assessment, protein assessment and other nutrient supplementation (such as β blocker, testosterone and oxandrolone, immunonutrition, vitamins) of CCI patients were reviewed, so as to provide reference for the treatment of CCI.

SERUM D-DIMER AS A TOOL FOR ASSESSMENT OF SEVERITY IN PATIENTS OF ACUTE PANCREATITIS

Introduction: Acute Pancreatitis (AP) is a potentially life threatening disease with varying severity of presentation from mild pain to persistent organ failure. D-dimer is an indirect measure of brin degradation products. It is a stable molecule with half-life of 4-8 hours. Material &amp;Method: This is a prospective study done on 60 patients of acute pancreatitis treated at Department of General Surgery, Sir Sunderlal Hospital IMS BHU Varanasi, UPfrom the period of 2016 to 2018. Patients with diagnosis of APas per revised Atlanta classication were taken and D-dimer level was assessed at the time of presentation and patients were followed to assess the severity of disease and outcome. The D-dimer values were correlated with the Glasgow-Imrie score as well as the CTseverity index (CTSI) Result: Median value of D-dimer was found to be 3.68 mg/IFEU among the cases and 0.3 mg/IFEU among healthy volunteers. D-dimer levels increased as per CTSI severity score ranging from 2.97 to &gt;5.70 mg/IFEU along with increased mortality in patients whom D-dimer levels were found to be high. D-dimer also showed positive correlation with Glasgow–Imrie score. Conclusion: Determining the serum concentration of D-dimer on day of admission is helpful in earlier prediction and assessment of severity of AP.

Mortality in acute pancreatitis with persistent organ failure is determined by the number, type, and sequence of organ systems affected

BackgroundPersistent organ failure (POF) is the strongest determinant of mortality in acute pancreatitis (AP). There is a paucity of data regarding the impact of different POF attributes on mortality and the role of different characteristics of systemic inflammatory response syndrome (SIRS) in the risk of developing POF.ObjectiveWe aimed to assess the association of POF dynamic features with mortality and SIRS characteristics with POF.MethodsWe studied 1544 AP subjects prospectively enrolled at 22 international centers (APPRENTICE consortium). First, we estimated the association of onset, duration, and maximal score of SIRS with POF. Then, we evaluated the risk of mortality based on POF onset, duration, number, type, and sequence of organs affected. Analyses were adjusted for potential confounders.Results58% had SIRS, 11% developed POF, and 2.5% died. Early SIRS, persistent SIRS, and maximal SIRS score ≥ 3 were independently associated with higher risk of POF (p < 0.05). Mortality risk in POF was higher with two (33%, odds ratio [OR] = 10.8, 3.3–34.9) and three (48%, OR = 20.2, 5.9–68.6) organs failing, in comparison to single POF (4%). In subjects with multiple POF, mortality was higher when the cardiovascular and respiratory systems failed first or concurrently as compared to when the renal system failed first or concurrently with other organ (p < 0.05). In multivariate regression model, the number and sequence of organs affected in POF were associated with mortality (p < 0.05). Onset and duration of POF had no impact mortality.ConclusionIn AP patients with POF, the risk of mortality is influenced by the number, type, and sequence of organs affected. These results are useful for future revisions of AP severity classification systems.

Respiratory Distress in the Newborn with Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is inherited in a predominantly autosomal recessive manner with over 45 currently identified causative genes. It is a clinically heterogeneous disorder that results in a chronic wet cough and drainage from the paranasal sinuses, chronic otitis media with hearing impairment as well as male infertility. Approximately 50% of patients have situs inversus totalis. Prior to the development of chronic oto-sino-pulmonary symptoms, neonatal respiratory distress occurs in more than 80% of patients as a result of impaired mucociliary clearance and mucus impaction causing atelectasis and lobar collapse. Diagnosis is often delayed due to overlapping symptoms with other causes of neonatal respiratory distress. A work up for PCD should be initiated in the newborn with compatible clinical features, especially those with respiratory distress, consistent radiographic findings or persistent oxygen requirement and/or organ laterality defects

SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study

ObjectiveThere is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis...

Minimal residual disease negativity by next-generation flow cytometry is associated with improved organ response in AL amyloidosis

Light chain (AL) amyloidosis is caused by a small B-cell clone producing light chains that form amyloid deposits and cause organ dysfunction. Chemotherapy aims at suppressing the production of the toxic light chain (LC) and restore organ function. However, even complete hematologic response (CR), defined as negative serum and urine immunofixation and normalized free LC ratio, does not always translate into organ response. Next-generation flow (NGF) cytometry is used to detect minimal residual disease (MRD) in multiple myeloma. We evaluated MRD by NGF in 92 AL amyloidosis patients in CR. Fifty-four percent had persistent MRD (median 0.03% abnormal plasma cells). There were no differences in baseline clinical variables in patients with or without detectable MRD. Undetectable MRD was associated with higher rates of renal (90% vs 62%, p = 0.006) and cardiac response (95% vs 75%, p = 0.023). Hematologic progression was more frequent in MRD positive (0 vs 25% at 1 year, p = 0.001). Altogether, NGF can detect MRD in approximately half the AL amyloidosis patients in CR, and persistent MRD can explain persistent organ dysfunction. Thus, this study supports testing MRD in CR patients, especially if not accompanied by organ response. In case MRD persists, further treatment could be considered, carefully balancing residual organ damage, patient frailty, and possible toxicity.

Early versus delayed intervention in necrotizing acute pancreatitis complicated by persistent organ failure

BackgroundCurrent guidelines for the treatment of patients with necrotizing acute pancreatitis (NAP) recommend that invasive intervention for pancreatic necrosis should be deferred to 4 or more weeks from disease onset to allow necrotic collections becoming “walled-off”. However, for patients showing signs of clinical deterioration, especially those with persistent organ failure (POF), it is controversial whether this delayed approach should always be adopted. In this study, we aimed to assess the impact of differently timed intervention on clinical outcomes in a group of NAP patients complicated by POF. MethodsAll NAP patients admitted to our hospital from January 2013 to December 2017 were screened for potential inclusion. They were divided into two groups based on the timing of initial intervention (within 4 weeks and beyond 4 weeks). All the data were extracted from a prospectively collected database. ResultsOverall, 131 patients were included for analysis. Among them, 100 (76.3%) patients were intervened within 4 weeks and 31 (23.7%) underwent delayed interventions. As for organ failure prior to intervention, the incidences of respiratory failure, renal failure and cardiovascular failure were not significantly different between the two groups (P > 0.05). The mortality was not significantly different between the two groups (35.0% vs. 32.3%, P = 0.83). The incidences of new-onset multiple organ failure (8.0% vs. 6.5%, P = 1.00), gastrointestinal fistula (29.0% vs. 12.9%, P = 0.10) and bleeding (35.0% vs. 35.5%, P = 1.00), and length of ICU (30.0 vs. 22.0 days, P = 0.61) and hospital stay (42.5 vs. 40.0 days, P = 0.96) were comparable between the two groups. ConclusionIntervention within 4 weeks did not worsen the clinical outcomes in NAP patients complicated by POF.